TJTES 2020-1 by KAREPUBLISHING

ISSN 1306 - 696X

TURKISH JOURNAL of TRAUMA & EMERGENCY SURGERY Ulusal Travma ve Acil Cerrahi Dergisi

Volume 26 | Number 1 | January 2020

www.tjtes.org

TURKISH JOURNAL of TRAUMA & EMERGENCY SURGERY Ulusal Travma ve Acil Cerrahi Dergisi Editor-in-Chief Mehmet Kurtoğlu Editors M. Mahir Özmen Mehmet Eryılmaz Publication Coordinator Mehmet Eryılmaz Former Editors Ömer Türel, Cemalettin Ertekin, Korhan Taviloğlu, Recep Güloğlu Section Editors Anaesthesiology & ICU Güniz Meyancı Köksal, Mert Şentürk Cardiac Surgery Münacettin Ceviz, Murat Güvener Neurosurgery Ahmet Deniz Belen, Mehmet Yaşar Kaynar Ophtalmology Cem Mocan, Halil Ateş Ortopedics and Traumatology Mahmut Nedim Doral, Ali Erşen Plastic and Reconstructive Surgery Figen Özgür, Atakan Aydın Pediatric Surgery Aydın Yagmurlu, Ebru Yeşildağ Thoracic Surgery Alper Toker, Akif Turna Urology Ali Atan, Öner Şanlı Vascular Surgery Cüneyt Köksoy, Mehmet Kurtoğlu Emergency Medicine Burak Katipoğlu, Togay Evrin

www.tjtes.org

THE TURKISH ASSOCIATION OF TRAUMA AND EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ President (Başkan) Vice President (2. Başkan) Secretary General (Genel Sekreter) Treasurer (Sayman) Members (Yönetim Kurulu Üyeleri)

Orhan Alimoğlu Mehmet Eryılmaz Ali Fuat Kaan Gök Gökhan Akbulut Osman Şimşek Münevver Moran Adnan Özpek

ISSUED BY THE TURKISH ASSOCIATION OF TRAUMA AND EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ YAYIN ORGANI Owner (Ulusal Travma ve Acil Cerrahi Derneği adına Sahibi) Editorial Director (Yazı İşleri Müdürü) Managing Editor (Yayın Koordinatörü) Publication Secretary (Yayın Sekreteri) Emblem (Amblem) Correspondence address (Yazışma adresi)

Tel Fax (Faks)

Orhan Alimoğlu Orhan Alimoğlu M. Mahir Özmen Kerem Ayar Metin Ertem Ulusal Travma ve Acil Cerrahi Dergisi Sekreterliği Şehremini Mah., Köprülü Mehmet Paşa Sok., Dadaşoğlu Apt., No: 25/1, 34104 Şehremini, İstanbul +90 212 - 531 12 46 - 588 62 46 +90 212 - 586 18 04

p-ISSN 1306-696x • e-ISSN 1307-7945 • Included in Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), DOAJ, EBSCO, and Turkish Medical Index (Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), DOAJ, EBSCO ve TÜBİTAK ULAKBİM Türk Tıp Dizini’nde yer almaktadır.) Publisher (Yayımcı): KARE Yayıncılık (KARE Publishing) • www.kareyayincilik.com • Design (Tasarım): Ali Cangül • Graphics (Grafikler): Edibe Çomaktekin • Linguistic Editor (İngilizce Editörü): Suzan Atwood • Online Manuscript & Web Management (Online Dergi & Web): LookUs • Press (Baskı): Yıldırım Matbaacılık • Press date (Basım tarihi): January (Ocak) 2020 • This publication is printed on paper that meets the international standard ISO 9706: 1994 (Bu dergide kullanılan kağıt ISO 9706: 1994 standardına uygundur.)

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www.tjtes.org

INFORMATION FOR THE AUTHORS The Turkish Journal of Trauma and Emergency Surgery (TJTES) is an official publication of the Turkish Association of Trauma and Emergency Surgery. It is a peer-reviewed periodical that considers for publication clinical and experimental studies, case reports, technical contributions, and letters to the editor. Six issues are published annually.

manuscript title, author names and institutions and correspondence address, abstract in Turkish (for Turkish authors only), and title and abstract in English are uploaded to the Journal Agent system in the relevant steps. The main text includes Introduction, Materials and Methods, Results, Discussion, Acknowledgments, References, Tables and Figure Legends.

As from 2001, the journal is indexed in Index Medicus and Medline, as from 2005 in Excerpta Medica and EMBASE, as from 2007 in Science Citation Index Expanded (SCI-E) and Journal Citation Reports / Science Edition, and as from 2014 in EBSCOhost. Our impact factor in SCI-E indexed journals is 0.643 (JCR 2019). It is cited as ‘Ulus Travma Acil Cerrahi Derg’ in PubMed.

The cover letter must contain a brief statement that the manuscript has been read and approved by all authors, that it has not been submitted to, or is not under consideration for publication in, another journal. It should contain the names and signatures of all authors. The cover letter is uploaded at the 10th step of the “Submit New Manuscript” section, called “Upload Your Files”.

Submission of a manuscript by electronic means implies: that the work has not been published before (except in the form of an abstract or as part of a published lecture, review, or thesis); that it is not under consideration for publication elsewhere; and that its publication in the Turkish Journal of Trauma and Emergency Surgery is approved by all co-authors. The author(s) transfer(s) the copyright to the Turkish Association of Trauma and Emergency Surgery to be effective if and when the manuscript is accepted for publication. The author(s) guarantee(s) that the manuscript will not be published elsewhere in any other language without the consent of the Association. If the manuscript has been presented at a meeting, this should be stated together with the name of the meeting, date, and the place.

Abstract: The abstract should be structured and serve as an informative guide for the methods and results sections of the study. It must be prepared with the following subtitles: Background, Methods, Results and Conclusions. Abstracts should not exceed 200 words.

Manuscripts must be submitted in English. All submissions are initially reviewed by the editor, and then are sent to reviewers. All manuscripts are subject to editing and, if necessary, will be returned to the authors for answered responses to outstanding questions or for addition of any missing information to be added. For accuracy and clarity, a detailed manuscript editing is undertaken for all manuscripts accepted for publication. Final galley proofs are sent to the authors for approval. Unless specifically indicated otherwise at the time of submission, rejected manuscripts will not be returned to the authors, including accompanying materials. TJTES is indexed in Science Citation Index-Expanded (SCI-E), Index Medicus, Medline, EMBASE, Excerpta Medica, and the Turkish Medical Index of TUBITAK-ULAKBIM. Priority of publications is given to original studies; therefore, selection criteria are more refined for reviews and case reports. Submission Fee: In order to further improve the quality and accessibility of the journal, a fee will be charged as a contribution to the cost of production. This fee will be charged during the process of application of submitted articles and will be charged regardless of eventual acceptance/rejection of the manuscript. Foreign authors can complete the article submission process after depositing USD 100.- to the USD account below. The article number released at the last stage of the article upload process must be written in the bank shipment description section. Recipient: ULUSAL TRAVMA VE ACIL CERRAHI DERNEGI IKTISADI ISLETMESI IBAN: TR02 0006 4000 0021 0490 9277 35 (USD) Turkish authors can complete the article submission process after depositing 500.- TL to the account below. The article number released at the last stage of the article upload process must be written in the bank shipment description section. Alıcı: ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ İKTİSADİ İŞLETMESİ IBAN: TR37 0006 4000 0021 0491 5103 66 (Türk Lirası Hesabı) Open Access Policy: Full text access is free. There is no charge for downloading the full text of printed material. Manuscript submission: TJTES accepts only on-line submission via the official web site (please click, www.travma.org.tr/en) and refuses printed manuscript submissions by mail. All submissions are made by the on-line submission system called Journal Agent, by clicking the icon “Online manuscript submission” at the above mentioned web site homepage. The system includes directions at each step but for further information you may visit the web site (http://www.travma.org/en/journal/). Manuscript preparation: Manuscripts should have double-line spacing, leaving sufficient margin on both sides. The font size (12 points) and style (Times New Roman) of the main text should be uniformly taken into account. All pages of the main text should be numbered consecutively. Cover letter,

Figures, illustrations and tables: All figures and tables should be numbered in the order of appearance in the text. The desired position of figures and tables should be indicated in the text. Legends should be included in the relevant part of the main text and those for photomicrographs and slide preparations should indicate the magnification and the stain used. Color pictures and figures will be published if they are definitely required and with the understanding that the authors are prepared to bear the costs. Line drawings should be professionally prepared. For recognizable photographs, signed releases of the patient or of his/her legal representatives should be enclosed; otherwise, patient names or eyes must be blocked out to prevent identification. References: All references should be numbered in the order of mention in the text. All reference figures in the text should be given in brackets without changing the font size. References should only include articles that have been published or accepted for publication. Reference format should conform to the “Uniform requirements for manuscripts submitted to biomedical journals” (http://www.icmje.org) and its updated versions (February 2006). Journal titles should be abbreviated according to Index Medicus. Journal references should provide inclusive page numbers. All authors, if six or fewer, should be listed; otherwise the first six should be listed, followed by “et al.” should be written. The style and punctuation of the references should follow the formats below: Journal article: Velmahos GC, Kamel E, Chan LS, Hanpeter D, Asensio JA, Murray JA, et al. Complex repair for the management of duodenal injuries. Am Surg 1999;65:972-5. Chapter in book: Jurkovich GJ. Duodenum and pancreas. In: Mattox KL, Feliciano DV, Moore EE, editors. Trauma. 4th ed. New York: McGraw-Hill; 2000. p. 735-62. Our journal has succeeded in being included in several indexes, in this context, we have included a search engine in our web site (www.travma.org.tr) so that you can access full-text articles of the previous issues and cite the published articles in your studies. Review articles: Only reviews written by distinguished authors based on the editor’s invitation will be considered and evaluated. Review articles must include the title, summary, text, and references sections. Any accompanying tables, graphics, and figures should be prepared as mentioned above. Case reports: A limited number of case reports are published in each issue of the journal. The presented case(s) should be educative and of interest to the readers, and should reflect an exclusive rarity. Case reports should contain the title, summary, and the case, discussion, and references sections. These reports may consist of maximum five authors. Letters to the Editor: “Letters to the Editor” are only published electronically and they do not appear in the printed version of TJTES and PUBMED. The editors do not issue an acceptance document as an original article for the ‘’letters to the editor. The letters should not exceed 500 words. The letter must clearly list the title, authors, publication date, issue number, and inclusive page numbers of the publication for which opinions are released. Informed consent - Ethics: Manuscripts reporting the results of experimental studies on human subjects must include a statement that informed consent was obtained after the nature of the procedure(s) had been fully explained. Manuscripts describing investigations in animals must clearly indicate the steps taken to eliminate pain and suffering. Authors are advised to comply with internationally accepted guidelines, stating such compliance in their manuscripts and to include the approval by the local institutional human research committee.

YAZARLARA BİLGİ Ulusal Travma ve Acil Cerrahi Dergisi, Ulusal Travma ve Acil Cerrahi Derneği’nin yayın organıdır. Travma ve acil cerrahi hastalıklar konularında bilimsel birikime katkısı olan klinik ve deneysel çalışmaları, editöryel yazıları, klinik olgu sunumlarını ve bu konulardaki teknik katkılar ile son gelişmeleri yayınlar. Dergi iki ayda bir yayınlanır. Ulusal Travma ve Acil Cerrahi Dergisi TÜBİTAK TR Dizinde taranmaktadır, ayrıca uluslararası indekslerde, 2001 yılından itibaren Index Medicus, PubMed’de, 2005 yılından itibaren EMBASE’de, 2007 yılından itibaren Web of Science, Science Citation Index-Expanded’de (SCI-E), 2014 yılından itibaren de EBSCOhost indeksinde dizinlenmektedir. 2018 Journal Citation Report IF puanımız 0.643 olmuştur. Dergide araştırma yazılarına öncelik verilmekte, bu nedenle derleme veya olgu sunumu türündeki yazılarda seçim ölçütleri daha dar tutulmaktadır. PUBMED’de dergi “Ulus Travma Acil Cerrahi Derg” kısaltması ile yer almaktadır. Dergiye yazı teslimi, çalışmanın daha önce yayınlanmadığı (özet ya da bir sunu, inceleme, ya da tezin bir parçası şeklinde yayınlanması dışında), başka bir yerde yayınlanmasının düşünülmediği ve Ulusal Travma ve Acil Cerrahi Dergisi’nde yayınlanmasının tüm yazarlar tarafından uygun bulunduğu anlamına gelmektedir. Yazar(lar), çalışmanın yayınlanmasının kabulünden başlayarak, yazıya ait her hakkı Ulusal Travma ve Acil Cerrahi Derneği’ne devretmektedir(ler). Yazar(lar), izin almaksızın çalışmayı başka bir dilde ya da yerde yayınlamayacaklarını kabul eder(ler). Gönderilen yazı daha önce herhangi bir toplantıda sunulmuş ise, toplantı adı, tarihi ve düzenlendiği şehir belirtilmelidir. Dergide İngilizce yazılmış makaleler yayınlanır. Tüm yazılar önce editör tarafından ön değerlendirmeye alınır; daha sonra incelenmesi için danışma kurulu üyelerine gönderilir. Tüm yazılarda editöryel değerlendirme ve düzeltmeye başvurulur; gerektiğinde, yazarlardan bazı soruları yanıtlanması ve eksikleri tamamlanması istenebilir. Dergide yayınlanmasına karar verilen yazılar “manuscript editing” sürecine alınır; bu aşamada tüm bilgilerin doğruluğu için ayrıntılı kontrol ve denetimden geçirilir; yayın öncesi şekline getirilerek yazarların kontrolüne ve onayına sunulur. Editörün, kabul edilmeyen yazıların bütününü ya da bir bölümünü (tablo, resim, vs.) iade etme zorunluluğu yoktur. Makale Gönderim Ücreti (Submission Fee): Dergimizin maliyetine katkı olarak, gönderilen makalelerde “başvurusu sırasında; kabul/red şartına bağlı olmaksızın” ücretlendirme yapılacaktır. Türk yazarlar aşağıdaki hesaba 500.- TL yatırdıktan sonra makale gönderim işlemini tamamlayabilirler. Alıcı: Ulusal Travma ve Acil Cerrahi Derneği IBAN: TR37 0006 4000 0021 0491 5103 66 (T. İş Bankası) (Banka gönderisi açıklama kısmına, makale yükleme işlemi sırasında son aşamadaki çıkacak makale numarası mutlaka yazılmalıdır). Açık Erişim İlkesi: Tam metinlere erişim ücretsizdir. Yayınlanan basılı materyali tam metni indirmek için herhangi bir ücret alınmaz. Yazıların hazırlanması: Tüm yazılı metinler 12 punto büyüklükte “Times New Roman” yazı karakterinde iki satır aralıklı olarak yazılmalıdır. Sayfada her iki tarafta uygun miktarda boşluk bırakılmalı ve ana metindeki sayfalar numaralandırılmalıdır. Journal Agent sisteminde, başvuru mektubu, başlık, yazarlar ve kurumları, iletişim adresi, Türkçe özet ve yazının İngilizce başlığı ve özeti ilgili aşamalarda yüklenecektir. İngilizce yazılan çalışmalara da Türkçe özet eklenmesi gerekmektedir. Yazının ana metnindeyse şu sıra kullanılacaktır: Giriş, Gereç ve Yöntem, Bulgular, Tartışma, Teşekkür, Kaynaklar, Tablolar ve Şekiller. Başvuru mektubu: Bu mektupta yazının tüm yazarlar tarafından okunduğu, onaylandığı ve orijinal bir çalışma ürünü olduğu ifade edilmeli ve yazar isimlerinin yanında imzaları bulunmalıdır. Başvuru mektubu ayrı bir dosya olarak, Journal Agent sisteminin “Yeni Makale Gönder” bölümünde, 10. aşamada yer alan dosya yükleme aşamasında yollanmalıdır. Başlık sayfası: Yazının başlığı, yazarların adı, soyadı ve ünvanları, çalışmanın yapıldığı kurumun adı ve şehri, eğer varsa çalışmayı destekleyen fon ve kuruluşların açık adları bu sayfada yer almalıdır. Bu sayfaya ayrıca “yazışmadan sorumlu” yazarın isim, açık adres, telefon, faks, mobil telefon ve e-posta bilgileri eklenmelidir. Özet: Çalışmanın gereç ve yöntemini ve bulgularını tanıtıcı olmalıdır. Türkçe özet, Amaç, Gereç ve Yöntem, Bulgular, Sonuç ve Anahtar Sözcükler başlıklarını; İngilizce özet Background, Methods, Results, Conclusion ve Key words başlıklarını içermelidir. İngilizce olarak hazırlanan çalışmalarda da Türkçe özet yer almalıdır. Özetler başlıklar hariç 190210 sözcük olmalıdır.

Tablo, şekil, grafik ve resimler: Şekillere ait numara ve açıklayıcı bilgiler ana metinde ilgili bölüme yazılmalıdır. Mikroskobik şekillerde resmi açıklayıcı bilgilere ek olarak, büyütme oranı ve kullanılan boyama tekniği de belirtilmelidir. Yazarlara ait olmayan, başka kaynaklarca daha önce yayınlanmış tüm resim, şekil ve tablolar için yayın hakkına sahip kişilerden izin alınmalı ve izin belgesi dergi editörlüğüne ayrıca açıklamasıyla birlikte gönderilmelidir. Hastaların görüntülendiği fotoğraflara, hastanın ve/veya velisinin imzaladığı bir izin belgesi eşlik etmeli veya fotoğrafta hastanın yüzü tanınmayacak şekilde kapatılmış olmalıdır. Renkli resim ve şekillerin basımı için karar hakemler ve editöre aittir. Yazarlar renkli baskının hazırlık aşamasındaki tutarını ödemeyi kabul etmelidirler. Kaynaklar: Metin içindeki kullanım sırasına göre düzenlenmelidir. Makale içinde geçen kaynak numaraları köşeli parantezle ve küçültülmeden belirtilmelidir. Kaynak listesinde yalnızca yayınlanmış ya da yayınlanması kabul edilmiş çalışmalar yer almalıdır. Kaynak bildirme “Uniform Requirements for Manuscripts Submitted to Biomedical Journals” (http:// www.icmje.org) adlı kılavuzun en son güncellenmiş şekline (Şubat 2006) uymalıdır. Dergi adları Index Medicus’a uygun şekilde kısaltılmalıdır. Altı ya da daha az sayıda olduğunda tüm yazar adları verilmeli, daha çok yazar durumunda altıncı yazarın arkasından “et al.” ya da “ve ark.” eklenmelidir. Kaynakların dizilme şekli ve noktalamalar aşağıdaki örneklere uygun olmalıdır: Dergi metni için örnek: Velmahos GC, Kamel E, Chan LS, Hanpeter D, Asensio JA, Murray JA, et al. Complex repair for the management of duodenal injuries. Am Surg 1999;65:972-5. Kitaptan bölüm için örnek: Jurkovich GJ. Duodenum and pancreas. In: Mattox KL, Feliciano DV, Moore EE, editors. Trauma. 4th ed. New York: McGraw-Hill; 2000. p. 735-62. Sizlerin çalışmalarınızda kaynak olarak yararlanabilmeniz için www.travma.org.tr adresli web sayfamızda eski yayınlara tam metin olarak ulaşabileceğiniz bir arama motoru vardır. Derleme yazıları: Bu tür makaleler editörler kurulu tarafından gerek olduğunda, konu hakkında birikimi olan ve bu birikimi literatüre de yansımış kişilerden talep edilecek ve dergi yazım kurallarına uygunluğu saptandıktan sonra değerlendirmeye alınacaktır. Derleme makaleleri; başlık, Türkçe özet, İngilizce başlık ve özet, alt başlıklarla bölümlendirilmiş metin ile kaynakları içermelidir. Tablo, şekil, grafik veya resim varsa yukarıda belirtildiği şekilde gönderilmelidir. Olgu sunumları: Derginin her sayısında sınırlı sayıda olgu sunumuna yer verilmektedir. Olgu bildirilerinin kabulünde, az görülürlük, eğitici olma, ilginç olma önemli ölçüt değerlerdir. Ayrıca bu tür yazıların olabildiğince kısa hazırlanması gerekir. Olgu sunumları başlık, Türkçe özet, İngilizce başlık ve özet, olgu sunumu, tartışma ve kaynaklar bölümlerinden oluşmalıdır. Bu tür çalışmalarda en fazla 5 yazara yer verilmesine özen gösterilmelidir. Editöre mektuplar: Editöre mektuplar basılı dergide ve PUBMED’de yer almamakta, ancak derginin web sitesinde yayınlanmaktadır. Bu mektuplar için dergi yönetimi tarafından yayın belgesi verilmemektedir. Daha önce basılmış yazılarla ilgili görüş, katkı, eleştiriler ya da farklı bir konu üzerindeki deneyim ve düşünceler için editöre mektup yazılabilir. Bu tür yazılar 500 sözcüğü geçmemeli ve tıbbi etik kurallara uygun olarak kaleme alınmış olmalıdır. Mektup basılmış bir yazı hakkında ise, söz konusu yayına ait yıl, sayı, sayfa numaraları, yazı başlığı ve yazarların adları belirtilmelidir. Mektup bir konuda deneyim, düşünce hakkında ise verilen bilgiler doğrultusunda dergi kurallarına uyumlu olarak kaynaklar da belirtilmelidir. Bilgilendirerek onay alma - Etik: Deneysel çalışmaların sonuçlarını bildiren yazılarda, çalışmanın yapıldığı gönüllü ya da hastalara uygulanacak prosedür(lerin) özelliği tümüyle anlatıldıktan sonra, onaylarının alındığını gösterir bir cümle bulunmalıdır. Yazarlar, bu tür bir çalışma söz konusu olduğunda, uluslararası alanda kabul edilen kılavuzlara ve T.C. Sağlık Bakanlığı tarafından getirilen yönetmelik ve yazılarda belirtilen hükümlere uyulduğunu belirtmeli ve kurumdan aldıkları Etik Komitesi onayını göndermelidir. Hayvanlar üzerinde yapılan çalışmalarda ağrı, acı ve rahatsızlık verilmemesi için neler yapıldığı açık bir şekilde belirtilmelidir. Yazı gönderme - Yazıların gönderilmesi: Ulusal Travma ve Acil Cerrahi Dergisi yalnızca www.travma.org.tr adresindeki internet sitesinden on-line olarak gönderilen yazıları kabul etmekte, posta yoluyla yollanan yazıları değerlendirmeye almamaktadır. Tüm yazılar ilgili adresteki “Online Makale Gönderme” ikonuna tıklandığında ulaşılan Journal Agent sisteminden yollanmaktadır. Sistem her aşamada kullanıcıyı bilgilendiren özelliktedir.

TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 26

Number - Sayı 1 January - Ocak 2020

Contents - İçindekiler ix-x

Editorial - Editörden Kurtoğlu M, Eryılmaz M, Özmen M

Experimental Studies - Deneysel Çalışma 1-8

Evaluation of rat major celluler prion protein for early diagnosis in experimental rat brain trauma model Deneysel beyin travması oluşturulan sıçanlarda erken tanı için sellüler prion protein’in değerlendirilmesi Kural A, Tekin Neijmann Ş, Toker A, Doğan H, Sever N, Sarıkaya S.

9-14

The effects of dexmedetomidine in increased intestinal permeability after traumatic brain injury: An experimental study Travmatik beyin hasarında artmış bağırsak geçirgenliğine deksmedetomidinin etkisi: Deneysel çalışma Karaca O, Doğan G

15-20

The importance of preliminary evaluation in developing ambulance staff training curriculum for developing countries: A survey in Uzbekistan Gelişmekte olan ülkeler için ambulans personeli eğitim ders programlarının geliştirilmesinde ön değerlendirmenin önemi: Özbekistan’da bir anket çalışması Jeon WC, Kim HJ, Park J, Kim KH, Shin DW, Park JM, Kim JE, Lee JS, Kim H

Original Articles - Orijinal Çalışma 21-29

Using pentraxin-3 for diagnosing acute appendicitis and predicting perforation: A prospective comparative methodological study Akut apandisit tanısını koymak ve perforasyonu öngörmek için Pentraxin-3 kullanımı: Bir ileriye yönelik karşılaştırmalı metodolojik çalışma Gül VO, Destek S

30-36

Comparison of epidural analgesia combined with general anesthesia and general anesthesia for postoperative cognitive dysfunction in elderly patients İleri yaş grubu hastalarda genel ve epidural anestezi ile yalnızca genel anestezi uygulamalarının nörokognitif fonksiyonlara etkilerinin karşılaştırılması Orhun G, Sungur Z, Koltka K, Savran Karadeniz M, Yavru HA, Gürvit H, Şentürk M

37-42

The thiol-disulphide homeostasis in patients with acute pancreatitis and its relation with other blood parameters Akut pankreatitli hastalarda tiyol-disülfid dengesi ve diğer kan parametreleri ile ilişkisi Ercan Haydar FG, Otal Y, Şener A, Pamukçu Günaydın G, İçme F, Atmaca Temrel T, Baran P, Erel Ö

43-49

Analysis of risk factors of mortality in abdominal trauma Abdominal travmada mortaliteyi etkileyen risk faktörlerinin analizi Gönültaş F, Kutlutürk K, Gök AFK, Barut B, Şahin TT, Yılmaz S

50-54

Spontaneous abdomen and abdominal wall hematomas due to anticoagulant/antiplatelet use: Surgeons’ perspective in a single center Antikoagülan/antiplatelet kullanımına bağlı spontan abdomen ve abdominal duvar hematomları: Tek merkez, cerrah perspektifi Çolakoğlu MK, Özdemir A, Kalcan S, Demir A, Demiral G, Pergel A

55-62

Should we still doubt the success of emergency oncologic colorectal surgery?: A retrospective study Acil onkolojik kolorektal cerrahinin başarısından hala şüphe etmeli miyiz?: Geriye dönük çalışma Acar N, Acar T, Kamer E, Cengiz F, Atahan K, Kar H, Hacıyanlı M

63-66

High C-reactive protein level as a predictor for appendiceal perforation Yüksek C-reaktif protein seviyesi apendiks perforasyonu için belirteç olabilir Özozan ÖV, Vural V

67-73

The characteristics of the patients in mass public shootings among coup attempt in Turkey: A single-center hospital response Türkiye’de darbe girişimi esnasında kitlesel silah yaralanmasına maruz kalan hastaların özellikleri: Tek merkezli hastane deneyimi Açıksarı K, Koçak M, Solakoğlu GA, Turan Ö, Erinc S, Ekinci Ö, Aydın E

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

vii

TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 26

Number - Sayı 1 January - Ocak 2020

Contents - İçindekiler 74-79 Investigation of firearm injury cases presented to training and research hospital’s emergency service Bir eğitim ve araştırma hastanesi acil servisine başvuran ateşli silah yaralanması olgularının incelenmesi Meral O, Sağlam C, Güllüpınar B, Aktürk ÖE, Beden S, Parlak İ 80-85 Factors affecting mortality in patients with traumatic diaphragmatic injury: An analysis of 92 cases Travmatik diyafragma yaralanması olan hastalarda mortalite ile ilişkili faktörler: 92 olgunun analizi Kaya S, Altın Ö, Altuntaş YE, Özdemir A, Cesur EE, Bildik N, Küçük HF 86-94 Predictive and prognostic value of L-lactate, D-dimer, leukocyte, C-reactive protein and neutrophil/ lymphocyte ratio in patients with acute mesenteric ischemia Akut mezenterik iskemi hastalarında L-laktat, D-dimer, lökosit, CRP ve nötrofil/lenfosit oranının prediktif ve prognostik değeri Destek S, Yabacı A, Abik YN, Gül VO, Değer KC 95-102 Traumatic upper extremity injuries: Analysis of correlation of mangled extremity severity score and disabilities of the arm, shoulder and hand score Travmatik üst ekstremite yaralanmaları: Ekstremite hasarlanması şiddet skoru ve kol, omuz ve el sakatlıkları arasında korelasyon analizi Hohenberger GM, Cambiaso-Daniel J, Schwarz AM, Boukovalas S, Seibert FJ, Konstantiniuk P, Cohnert T 103-108 Endoscopic treatment of postoperative biliary fistulas Ameliyat sonrası safra fistüllerinin endoskopik tedavisi Çolak Ş, Gürbulak B, Gök AFK, Çakar E, Bektaş H 109-114 The effects of early femoral nerve block intervention on preoperative pain management and incidence of postoperative delirium geriatric patients undergoing trochanteric femur fracture surgery: A randomized controlled trial Trokanterik femur kırığı operasyonu geçirecek yaşlı hastada erken dönemde yapılan femoral sinir blokajının ağrı yönetimi ve deliryum insidansına etkisi: Randomize kontrollü çalışma Uysal Aİ, Altıparmak B, Yaşar E, Turan M, Canbek U, Yılmaz N, Gümüş Demirbilek S 115-122 Factors predicting reoperation after hand flexor tendon repair El fleksör tendon onarımı sonrası reoperasyonu öngören faktörler Çalışkan Uçkun A, Yurdakul FG, Ergani HM, Güler T, Yaşar B, Başkan B, Bodur H, Ünlü RE 123-129 Upper extremity replantation results in our series and review of replantation indications Üst ekstremite major replantayon sonuçlarımız ve endikasyonların tekrar gözden geçirilmesi Okumuş A, Özkan AC

Case Series - Olgu Serisi 130-136 Mid-term results of displaced acetabulum fractures surgically treated using anterior intra-pelvic approach (modified Stoppa) Anterior intra-pelvik yaklaşımla (modifiye Stoppa) tedavi edilen deplase asetabulum kırıklarının orta dönem sonuçları Çağlar Ö, Kamacı S, Bekmez Ş, Tokgözoğlu AM, Atilla B, Acaroğlu E 137-143 ong-term comparative study of internal fixation with Kirschner wires or cannulated screws for displaced medial epicondyle fractures of the humerus in children: A 10-year follow-up of 42 cases Pediatrik deplase mediyal epikondil kırıklarının cerrahi tedavisinde Kirschner teli veya kanüllü vida ile internal tespitin uzun dönem sonuçlarının karşılaştırmalı çalışması: 42 olgunun 10 yıllık takip sonuçları Ergin ÖN, Demirel M, Şentürk F, Bayram S, Bilgili F

Case Reports - Olgu Sunumu 144-147 Castleman’s disease presenting with mechanical intestinal obstruction: A rare case Mekanik bağırsak tıkanmasıyla başvuran Castleman hastalığı: Nadir bir olgu Kartal A, Atlı E, Vural G, Ferhatoğlu MF, Filiz Aİ 148-151 A rare case of acute mechanical intestinal obstruction: Colonic endometriosis Nadir görülen bir akut mekanik intestinal obstrüksiyon olgusu: Kolonik endometriozis Buldanlı MZ, Özemir İA, Yener O, Dölek Y. 152 Reviewer List of 2019

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Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

EDITORIAL

Dear Readers, We are proud to recognize the achievement of 25 years of publication of our journal, which was started in 1995. We would especially like to thank our editors, who have contributed to the development of the journal since the release of the first issue. The diversity and strength of the articles submitted to us is a mark of our recognition and significance in the world. When measuring our journal according to international parameters, we are happy to report that the scientific value and visibility has grown over the last 25 years. According to the latest Clarivate Analytics Journal Citation Report, our impact factor increased to 0.643 in 2019, which indicates more citations from colleagues. Our aim is to continue to increase the profile, excellence, and number of citations of our journal. In order to improve the quality and accessibility of the journal, a fee will be charged in the upcoming year for the evaluation and printing of manuscripts as a contribution to the costs of the journal. In order to keep our journal alive and to ensure its development at the international level, we felt obliged to implement such a procedure, which is common to many journals. The editorial board wishes you a happy and successful new year. We hope that your interest and support of our association and our journal will continue to grow. Regards, Mehmet Kurtoğlu, Mehmet Eryılmaz, Mahir Özmen

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

EDİTÖRDEN

Sevgili Okurlarımız, 1995 yılından beri çıkan dergimizin 25. yılını tamamlamış bulunuyoruz. Başlangıçtan beri dergimizin gelişmesine katkısı olan editörlerimize teşekkürlerimi sunarız. Dünyadaki tanınırlığımız, elde ettiğimiz yazıların çeşitliliği ve yoğunluğunda anlaşılmaktadır. Dergimizi uluslararası parametrelere göre değerlendirdiğimizde bilimsel seviyesinin 25 yıl içinde ciddi bir şekilde arttığını mutlulukla görmekteyiz. 2019 yılında Journal Scitation Reporta göre Impact Factor’ümüz (IF) 0,643’e yükselmiştir. Amacımız dergimizin daha da bilinir, okunur ve refere edilme oranını yükseltmek olacaktır. Kalitenin ve erişilebilirliliğinin iyileştirilebilmesi için derginin maliyetine katkı olarak gönderilen yazıların değerlendirilmesi ve basılması için ücretlendirme yoluna gidilecektir. Dergimizi yaşatabilmek ve uluslararası seviyede gelişmesini sağlayabilmek için birçok dergide de uygulanan böyle bir yolu uygulamak mecburiyetinde hissettik. Editörler kurulu olarak sizlere başarılı ve mutlu yıllar dileriz. Derneğimiz ve Dergimize olan ilgi ve desteğinizin artarak devam etmesini bekleriz. Saygılarımızla, Mehmet Kurtoğlu, Mehmet Eryılmaz, Mahir Özmen

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

EXPERIMENTAL STUDY

Evaluation of rat major celluler prion protein for early diagnosis in experimental rat brain trauma model Alev Kural, M.D.,1 Şebnem Tekin Neijmann, M.D.,1 Aysun Toker, M.D.,2 Halil Doğan, M.D.,3 Nurten Sever, M.D.,4 Sezgin Sarıkaya, M.D.5 1

Department of Biochemistry, Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul-Turkey

Department of Biochemistry, Karaman Private Hospital, Karaman-Turkey

Department of Emergency Medicine, Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul-Turkey

Department of Pathology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul-Turkey

Department of Emergency Medicine, Yeditepe University Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: Although traumatic brain injury (TBI) is an important problem, there has been no widespread utilization of neurobiomarkers to aid the diagnosis of TBI. This study was conducted to evaluate serum S100B and prion protein (PrPC) levels in rats with TBI. METHODS: In this study, 15 albino rats were categorized into three groups as follows: sham-operated (1), control (6) and trauma (8) groups. The TBI model was based on the modified free falling model. S100B, PrPC levels were measured using ELISA. Brain specimens were obtained for the pathological examination. RESULTS: Serum S100B and PrPC levels were found to increase in T group at both 2h and 24h after trauma (p<0.002, p<0.002, respectively). We also found higher histopathological injury scores of brain tissues in the T group. Only a positive correlation was found between serum PrPC levels and the extent of brain injury (p=0.039, r=0.731). Using ROC analysis, among the two serum markers investigated, both of them revealed the same sensitivity and specificity for diagnosing TBI. CONCLUSION: The changes in serum S100B and PrPC levels showed good sensitivity in our experimental model. Therefore, PrPC could be helpful in the early prognostic prediction in patients with TBI. Further studies are needed to test our findings in humans following TBI (penetrating bodies, blunt trauma) to definitively acknowledge it as a reliable biomarker and its subsequent diagnostic utility. Keywords: Major cellular protein prion (PrPC); S100B; traumatic brain injury.

INTRODUCTION Traumatic brain injuries may cause longterm neurological morbidities by primary and secondary mechanisms. Primary damage occurs at the time of the incident due to mechanical injury and cannot be prevented, although secondary injury is induced by the biochemical and physiological process can be avoided.[1] TBI is a very important public health issue because of its effects on extensive psychological, physical and social impacts with a high economic concern.[2] Moreover, according to the WHO, many diseases will be overshot by TBI as the major cause of death and disability by the year 2020. Neu-

rological examination and neuroimagining tools are the main implements of the diagnosis of TBI in the acute period. One of them, computed tomography (CT) scanning, is prone to radiation exposure and has low sensitivity in some cases. The other tool, magnetic resonance imaging (MRI), can induce useful information, but it is restricted by cost, limited availability, and concerns to use in unstable patients.[3,4] There is limited knowledge in the early diagnosis and diagnostic and prognostic tools for risk stratification of TBI patients. Therefore, to validate and introduce rapid diagnosis employing biomarkers from blood tests into the clinical setting is the key for this population. Although several studies exploring many promising

Cite this article as: Kural A, Tekin Neijmann Ş, Toker A, Doğan H, Sever N, Sarıkaya S. Evaluation of rat major celluler prion protein for early diagnosis in experimental rat brain trauma model. Ulus Travma Acil Cerrahi Derg 2020;26:1-8. Address for correspondence: Alev Kural, M.D. Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Biyokimya Kliniği, İstanbul, Turkey Tel: +90 212 - 414 71 71 / 5126 E-mail: alevkural@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):1-8 DOI: 10.5505/tjtes.2018.46923 Submitted: 20.09.2018 Accepted: 20.12.2018 Online: 31.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Kural et al. Evaluation of rat major celluler prion protein (PrPC) for early diagnosis in experimental rat brain trauma model

biomarkers,[5,6] there is a lack of any Food and Drug Administration–approved biomarkers for clinical use.[6,7] A new confirmed blood neuro biomarkers may decline unnecessary radiation exposure and provide an opportunity for early diagnosis and by this way, care of patients with TBI may be improved. S100B is the major low-affinity calcium-binding protein in astrocytes[8] that contributes to regulating intracellular levels of calcium; it is considered as a marker of astrocyte injury or death. S100B is one of the most largely studied biomarkers in brain injury.[9–14] Elevated levels of S100B in serum have been associated with an increased incidence of the postconcussive syndrome and problems with cognition.[15,16] Moreover, studies have reported that serum levels of S-100B are related to MRI abnormalities and with neuropsychological examination disturbances after TBI.[17,18] Notable interactions between elevated serum levels of S100B and CT abnormalities were spotted by several studies.[19,20] It has been suggested that assaying S100B concentration to clinical decision tools for mild TBI patients could potentially diminish the number of CT scans by 30%.[19] We should note that these results have not been consistently reproduced and no relations between S100B and CT abnormalities have been spotted by many other investigators.[21–23] Accumulating evidence has shown that cellular prion protein (PrPC) host-coded membrane-bound glycoprotein plays pivotal roles in processes, such as copper binding, the regulation of cell death and the modulation of several signal transduction pathways.[24–26] However, the actual physiological function of this stays is unknown. In vitro and in vivo studies have reported that interaction between PrPC and amyloid-β oligomers could be a useful pathology of Alzheimer’s disease because of the high receptor affinity of PrPC for these oligomers.[27] The main objective of this study was to determine the feasibility of using circulating S100B and PrPC levels at 2h and 24 h in rats following TBI.

MATERIALS AND METHODS Fifteen female Wistar albino rats, weighing 220–230 g, from the Animal Laboratory of YeditepeUniversity (İstanbul Turkey), were randomly divided into three groups. The first group was sham-operated (S, n=1) group in which only a craniotomy was performed, the others control (C, n=6) and trauma (T, n=8) groups. All the rats were put under environmentally controlled conditions in a 12/12 h light/dark and granted free access to food and water. This study was approved by the Animal Care and Ethics Committee of Yeditepe University School of Medicine (date: 01.03.2016, no: 522).

Experimental Procedure of TBI A special weight-drop device developed by Marklund et al.[28] was used to deliver a standard diffuse traumatic injury. Under ketamine hydrochloride anesthesia (80 mg/kg) and xyslazine 2

(10 mg/kg) intraperitoneally (i.p.), rats were placed in a prone position. A craniotomy (6X9 mm2), centered over the right parietal cortex at bregma -3.5 and 3.5 mm lateral to the midline, was done using a dental drill. The weight-drop device, a 5 g weight, was allowed to fall freely from a height of 50 cm to induce TBI. The device’s aim is to prevent bouncing of the weight by allowing a single compression. Animals that survived after 24 h were the ones to be used in this study and animals that died during trauma and observation were eliminated. Blood samples were collected before and after trauma (after 2nd and 24th hrs, 1 mL sample every time). All serum samples were centrifuged and stored at -80ºC using an ultracold freezer. We noted physiological parameters of the rats after 24 h and the rats were anaesthetized with an i.p. injection of ketamine hydrochloride. After intracardiac blood drawing for analysis, all rats were sacrificed, and the brains were carefully taken out for pathological examination. Blood serums were held at -80 ºC till analysis. Both serum S100B (Bioassay Technology Laboratory E0075Ra, Rat S100 Calcium Binding Protein B) and PrPC (Bioassay Technology Laboratory E1368Ra, Rat Majör Prion Protein (PRNP)) levels were measured with ELISA method.

Histopathological Examination The intact brain was finally placed into 10% formaldehyde. The extent of brain damage was detected by morphological findings. Tissue samples were obtained from the hippocampus, pons and cerebellum. Axial sections were stained with hematoxylin and eosin (H&E). Stained specimens were examined blindly under an Olympus BX40 light microscope by a pathologist. In the histopathological examination of brain tissues, edema, hemorrhage, neuronal damage, vascular congestion, retraction ball-diffuse axonal damage and their extensity were estimated. The semi-quantitative scores reflect the approximate percentage of axonal, vascular and neuronal changes observed in the section. Results were scored as grade 0 (no changes), grade 1 (dilatation), grade 2 (dilatation and stasis), grade 3 (dilatation, statis and parenchymal hemorrhage).

Statistical Analyses Statistical analyses were performed using MedCalc Statistical Software version 12.7.7 (MedCalc Software bvba, Ostend, Belgium; http://www.medcalc.org; 2013). Descriptive analysis was used to determine continuous variables (mean, Standard deviation, minimum and maximum). Nonparametric statistical analyses were used: some differences between two distinct groups were regulated using the Mann-Whitney U test; differences between more than two groups were determined using the Kruskal-Wallis test. Differences between two dependent groups were determined using the Wilcoxon test; differences between more than two dependent groups were determined using the Friedman test. A p-value of <0.05 was considered statistically significant. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Kural et al. Evaluation of rat major celluler prion protein (PrPC) for early diagnosis in experimental rat brain trauma model

Table 1. Serum biochemical parameter levels in groups

24h

p* p1 p2 p3

Mean±SD Mean±SD Mean±SD Median (Min-Max) Median (Min-Max) Median (Min-Max) S100B (ng/L) Control

5.09±0.7 5.1 (4.2–6.2)

Trauma

4.9±0.6 4.6 (4.2–6.2)

11.6+1.1 11.4 (10.2–13.5) 81.6±21.9 81.7 (48.6–118.6)

11.8±5.2

0.042 0.028 0.058 0.753

13.1 (5.2–17.2) 411.8±141.6

0.001 0.012 0.012 0.012

387.7 (235.7–585.9)

PRNP (ng/mL) Control

1.4±0.3 1.3 (1–1.8)

Trauma

1.3±0.2 1.2 (1–1.8)

1.1±0.09 1.09 (1.02–1.3)

2.4±0.3

7.7±0.7 7.7 (6.8–9.3)

0.006 0.173 0.028 0.028

2.4 (2.1–2.7) 24.6±5.7

0.001 0.012 0.012 0.012

25.7 (16.1–31.7)

Friedman test, 10h-2h, 20h-24h, 32h-24h (Wilcoxon test). S100B: Bioassay Technology Laboratory E0075Ra, Rat S100 Calcium Binding Protein B; PRNP: Rat majör prion protein; SD: Standard deviation; Min: Minimum; Max: Maximum.

ROC curves were constructed using both trauma and control subject serum S100B and PrPC levels in an attempt to form a specificity- sensitivity relationship; areas under the ROC curve were calculated according to standard methods.[18] The diagnostic accuracy of the serum levels determined at study entry was expressed as the area under the receiver operating characteristic curve (AUC), which was derived from logistic regression analysis.[19] These values were calculated for the cut-off from the AUCs.

RESULTS Physiological Measurements No rats died throughout all the experimental experience. There was no difference between the physiological measurements of rats before trauma and at the end of the experiment apropos weight, respiration, heart rate and rectal temperature. 450 400

Biochemical Analyses Serum S100B and PrPC levels and histopathological scores for each group were shown in (Table 1). There were no significant differences in using serum S100B and PrPC levels at the beginning of this experiment in both groups. We found statistically significant differences in these markers at both 2nd and 24th hrs of the experiment when compared to C and T groups (p<0.001) (Fig. 1, 2). In control and trauma groups, serum S100B and PrPC levels were statistically significantly different when compared 0, 2 and 24hrs (Friedman p<0.05). In the trauma group, there were significant differences at both S100B and PrPC levels at dual comparisons using all sampling time (0h-2h, 0h-24h, 2h-24h) (Wilcoxon p<0.016, after Bonferroni correction). However, these differences were not observed in the control group.

Control Trauma

30 25 PrPC Levels (ng/mL)

350 S100B Levels (ng/L)

Control Trauma

300 250 200 150 100

20 15 10 5

50 0

0 0h

24h

Figure 1. Serum S100B levels at the all time points in both gropus.

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

24h

Figure 2. Serum PrPC levels at the all time points in both gropus.

Kural et al. Evaluation of rat major celluler prion protein (PrPC) for early diagnosis in experimental rat brain trauma model

Table 2. The comparison of biochemical parameters differences at time of sampling according to groups

group, 6 of 8 rats have grade 2, and 2 of 8 rats have grade 3 features.

DISCUSSION

Control

Trauma

Mean±SD Median (Min-Max)

S100B (ng/L) 0–2 0–24

-6.5±1.1

-76.7±22.3

-6.4 (-8.3–-5.0)

-77.3 (-114.4–-43.3)

-6.7±5.8 -8.2 (-13–0.9)

2–24

0.001

-406.9±142.2

0.001

382.8 (-581.7–-230.4)

-0.2±6.2

-330.2±122.6

-1.8 (-6.1–7.4)

-304.6 (-471.9–-187.1)

0.001

PrPC (ng/mL) 0–2

0.2 (-0.3–0.7)

0–24

-6.4±0.9

0.001

-6.3 (-8.3–-5)

-1.01±0.5 -1 (-1.7–-0.5)

2–24

0.2±0.3

-23.3±5.7

0.001

-24.6 (-30.1–-14.8)

-1.3±0.2

-16.9±5.9

-1.3 (-1.5–-0.9)

-17.1 (-24.9–-8.9)

0.001

*Mann-Whitney U test. S100B: Bioassay Technology Laboratory E0075Ra, Rat S100 Calcium Binding Protein B; PrPC: Cellular prion protein; SD: Standard deviation; Min: Minimum; Max: Maximum.

We found significant variations of serum S100B and PrPC levels between 0h-2h, 0h-24h and 2h-24h in both control and trauma groups (Table 2). The only significant correlation was found between PrPc levels and extent of injury in the trauma group (p=0.039, r=0.731). To compare S100B and PrPC levels for the prediction of TBI, we performed ROC curves. The two serum markers investigated revealed similar sensitivity and specificity for diagnosing TBI (Table 3, Fig. 3).

Histopathological Results Pathological examination results were significantly higher in the trauma group after 24 h as expected. Light microscope images of stasis and bleeding are shown in Figure 4. We found grade 1 features in group C and S rats. In the trauma

There are several models for mimicking the brain injury in humans, such as lateral and central fluid impact, wounding with hard objects, acceleration (weight drop from a height), injection, cold injury, local stress, and penetrating injury models. The acceleration model has been thought to be idle for diffuse brain injury.[29] Thus, it was chosen in our study. Our results showed that both serum S100B and PrPC levels were found significantly increased after trauma at both 2 and 24 hrs. We also found a significant positive correlation between serum PrPC levels and the extent of brain injury at all time points. We also measured the same sensitivity and specificity for the diagnosis of TBI. Traumatic brain injury that arises from a sudden external force is a set of secondary functional and/or pathological amendments within the brain. It represents an important problem in public health.[30] Research on mild TBI has examined the role of biomarkers as prognostic and diagnostic tools for brain damage, such as glial fibrillary acidic protein, neuron-specific enolase, ubiquitin C-terminal hydrolase-L1, Tau protein and the S100B protein.[31] They could have potentially predictive effects about damage to reduce CT use in TBI diagnosis.[32] S100B is one of the most studied biomarkers for a brain injury to date and could be useful for the diagnosis of TBI.[33] S100B is a calcium-binding protein with a biological half-life of 30–120 min. It is synthesized Schwann cells primarily, and in astroglial cells.[34] After blood–brain barrier injury or neuronal damage, this protein is released into the bloodstream.[35] Although S100B is still a reassuring connected marker, its utility in the setting of multiple traumas remains questionable because it is also elevated in trauma patients without head injuries.[36–38] In addition to these findings, there are studies on serum and the cerebrospinal fluid. There is a clear positive interaction with the degree of brain damage.[39,40] The exact role of S100B has protein in the pathogenesis of TBI remains unclear. Excessive production of S100B from astrocytes in brain injury may generate toxic milieu. S100B have potential effects on both stimulation of the production of proinflammatory cytokines and direct neurotoxicity.[41] Several findings indicated that S100B protein is important in the inflammatory reaction in the earlier period and associated with the secondary brain injury.[39,40]

Table 3. Diagnostic performance of S100B and PrPC at 24h

AUC p-value Cut-off*

Sensitivity

95% Lower CI

95% Upper CI Specificity

95% Lower CI

95% Upper CI

S100B 0.816 0.018 235.667 85.71 42.1 99.6 85.71 42.1 99.6 PRNP 0.878 <0.001 16.136 85.71 42.1 99.6 85.71 42.1 99.6 *Sensitivity, specificity, and predictive values were calculated for the cutoff, which represented the best discrimination as derived from the receiver operating characteristic curves. The area under the receiver operating characteristic curves (AUC), confidence interval (CI). S100B: Bioassay Technology Laboratory E0075Ra, Rat S100 Calcium Binding Protein B; PRNP: Rat majör prion protein; PrPC: Cellular prion protein.

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Kural et al. Evaluation of rat major celluler prion protein (PrPC) for early diagnosis in experimental rat brain trauma model

s100-24

100

Sensitivity: 85.7 Specificity: 85.7 Criterion: >235.667

Sensitivity: 85.7 Specificity: 85.7 Criterion: >16.136

Sensitivity

PRNP-24

100

0 0

100

100-Specificity

100

100-Specificity

Figure 3. Evaluation of serum S100B and PrPC for the diagnosis of TBI. Receiver operating characteristic curves were drawn with the data of these markers from all rats. AUC, the area under curve.

Figure 4. Axial sections were stained with hematoxylin and eosin (H&E). Light microscope (BX40) images of stasis and bleeding respectively.

It was commented on the potential of S100B to reduce CT scanning in mild TBI.[42] S100B is a useful biomarker not only in adults but also in children. Even though S100B is quite sensitive, it has poor specificity in this population. S100B could be a marker to prevent an intracranial injury but cannot be used as the sole marker owing to its specificity.[43] However, only Scandinavian guidelines include its early measurement in the initial clinical management of minimal, mild and moderate TBI to rule out the presence of intracranial lesion.[44] In addition to this, the American College of Emergency Physicians recommends the use of the CT scan on patients with mild TBI only when levels of S100B in serum are >0.10 Îźg/L.[45] Interestingly, post-mortem cerebrospinal fluids S100B levels are significantly elevated, after a fatal TBI.[46] PrPC is a ubiquitous glycoprotein distributed throughout many cell types, especially within the central nervous system Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

(CNS).[47] PrPC may play a decisive but unclear role in T-cell function because of T cell activation. However, interestingly, PrPC knockout mice have only minor alterations in immune function.[48] Physiological levels of PrPC exhibit a neuroprotective effect following hypoxic brain damage in vivo.[49] The mechanism underlying neuroprotection involves a copperbinding activity that protects cells from oxidative damage.[25] Moreover, membrane-associated PrPC with an extracellular glycosyl-phosphatidylinositol anchor may release into the systemic circulation under shear forces. Therefore PrPC may serve as a potential biomarker for TBI.[50] However, it was demonstrated in an animal model that plasma PrPC is a potential biomarker for determining primary Blast-induced TBI. [50] The applied force on the brain tissue may dislocate PrPC from its neuronal lipid rafts and allow the protein to collect within the systemic circulation. Therefore, the circulating levels could be used as a potential biomarker for mild TBI diag5

Kural et al. Evaluation of rat major celluler prion protein (PrPC) for early diagnosis in experimental rat brain trauma model

nosis.[51] The authors also reported that a mild positive interaction correlation between plasma PrPC levels and increasing blast intensity.[50] Moreover, neurodegenerative changes after TBI is also associated with elevated plasma PrPC levels.[52] Recently, it was suggested that PrPC is important in mediating TBI related pathology.[53] On the other hand, PrPC is expressed on endothelial cells and could change at the other pathological conditions, such as cerebrovascular disease, vascular endothelial damage, or hypertension.[54] TBI may affect anyone and can enhance the risk of certain brain diseases. TBI may alter the brain, producing pathologies, such as energy depletion, ionic imbalances, toxic aggregates, inflammation, and cell death. Thus, brain trauma may result in disease-causing and disease-accelerating capabilities, ultimately being the main reason for these affected individuals to develop neurodegenerative disorder.[55] PrPC has been reported to be upregulated following focal cerebral ischemia; thus, it is possible that the rise in plasma PrPC content may be partially attributed to damaged ischemic regions in the brain as a result of blast exposure.[56] Because the extent of blast-induced damage in the brain is unclear, it is possible that PrPC mRNA and protein expression may also be affected. It is certain, however, that the rise in PrPC concentration is yet another part of the unique pathology complex associated with primary bTBI.[56–64] Although there are many studies in literature for s100B after TBI, there are limited studies about S100B and prion protein C together. Detecting cellular prion protein as a biomarker could be thought important for TBI. As prion protein levels lead clinicians to diagnose TBI earlier and to forecast neurodegenerative disease. In addition, we know that S100 B has poor specificity. Therefore, using several biomarkers simultaneously is useful for early diagnose and other clinical aspects. Further studies are needed to test our findings in humans following TBI (penetrating bodies, blunt trauma) to definitively acknowledge it as a reliable biomarker and its subsequent diagnostic utility. To date, several biomarkers have been investigated, but none of them has been definitively established as having clinically practical screening qualities.[33] We report that mean PrPC concentration is significantly increased compared with controls at both 2nd and 24th hrs after insult. Higher PrPC levels found after TBI may arise from its neuroprotective role in brain tissue. In the literature, it was shown that raised PrPC levels in blast TBI at 24th h. To our knowledge, this is the first study investigating PrPC levels at the early period following injury. In this study, we demonstrated circulating PrPC as a potential biomarker for early diagnosis of TBI. We also reported a positive correlation between PrPC and the extent of the injury. Ethics Committee Approval: Approved by the local ethics committee (date: 01.03.2016, no: 522). 6

Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.K., Ş.T.N.; Design: A.K.; Supervision: Ş.T.N.; Fundings: S.S.; Materials: H.D.; Data: S.S.; Analysis: A.K., N.S.; Literature search: A.T.; Writing: A.K., A.T.; Critical revision: A.K. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

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39. Lima JE, Walz R, Tort A, Souza D, Portela L, Bianchin MM, et al. Serum and cerebrospinal fluid S100B concentrations in patients with neurocysticercosis. Braz J Med Biol Res 2006;39:129−35. 40. Chen DQ, Zhu LL. Dynamic change of serum protein S100b and its clinical significance in patients with traumatic brain injury. Chin J Traumatol 2005;8:245−8. 41. Van Eldik LJ, Wainwright MS. The Janus face of glial-derived S100B: beneficial and detrimental functions in the brain. Restor Neurol Neurosci 2003;21:97−108. 42. Undén J, Romner B. Can low serum levels of S100B predict normal CT findings after minor head injury in adults?: an evidence-based review and meta-analysis. J Head Trauma Rehabil 2010;25:228−40. 43. Manzano S, Holzinger IB, Kellenberger CJ, Lacroix L, Klima-Lange D, Hersberger M, et al. Diagnostic performance of S100B protein serum measurement in detecting intracranial injury in children with mild head trauma. Emerg Med J 2016;33:42−6. 44. Undén J, Ingebrigtsen T, Romner B; the Scandinavian Neurotrauma Committee(SNC). Scandinavian guidelines for initial management of minimal, mild and moderate head injuries in adults: an evidence and consensus-based update. BMC Med 2013;11:50. 45. Jagoda AS, Bazarian JJ, Bruns JJ Jr, Cantrill SV, Gean AD, Howard PK, et al; American College of Emergency Physicians; Centers for Disease Control and Prevention. Clinical policy: neuroimaging and decisionmaking in adult mild traumatic brain injury in the acute setting. Ann Emerg Med 2008;52:714−48. 46. Sieber M, Dreßler J, Franke H, Pohlers D, Ondruschka B. Post-mortem biochemistry of NSE and S100B: A supplemental tool for detecting a lethal traumatic brain injury? J Forensic Leg Med 2018;55:65−73. 47. Yusa S, Oliveira-Martins JB, Sugita-Konishi Y, Kikuchi Y. Cellular prion protein: from physiology to pathology. Viruses 2012;4:3109−31. 48. Isaacs JD, Jackson GS, Altmann DM. The role of the cellular prion protein in the immune system. Clin Exp Immunol 2006;146:1−8. 49. McLennan NF, Brennan PM, McNeill A, Davies I, Fotheringham A, Rennison KA, et al. Prion protein accumulation and neuroprotection in hypoxic brain damage. Am J Pathol 2004;165:227−35. 50. Pham N, Sawyer TW, Wang Y, Jazii FR, Vair C, Taghibiglou C. Primary blast-induced traumatic brain injury in rats leads to increased prion protein in plasma: a potential biomarker for blast-induced traumatic brain injury. J Neurotrauma 2015;32:58−65. 51. Pham N, Akonasu H, Shishkin R, Taghibiglou C. Plasma soluble prion protein, a potential biomarker for sport-related concussions: a pilot study. PLoS One 2015;10:e0117286. 52. Sidaros A, Skimminge A, Liptrot MG, Sidaros K, Engberg AW, Herning M, et al. Long-term global and regional brain volume changes following severe traumatic brain injury: A longitudinal study with clinical correlates. NeuroImage 2009;44:1−8. 53. Rubenstein R, Chang B, Grinkina N, Drummond E, Davies P, Ruditzky M, et al. Tau phosphorylation induced by severe closed head traumatic brain injury is linked to the cellular prion protein. Acta Neuropathol Commun 2017;5:30. 54. Simák J, Holada K, D’Agnillo F, Janota J, Vostal JG. Cellular prion protein is expressed on endothelial cells and is released during apoptosis on membrane microparticles found in human plasma. Transfusion 2002;42:334−42. 55. Stein TD, Montenigro PH, Alvarez VE, Xia W, Crary JF, Tripodis Y, et al. Beta-amyloid deposition in chronic traumatic encephalopathy. Acta Neuropathol 2015;130:21−34. 56. Weise J, Crome O, Sandau R, Schulz-Schaeffer W, Bähr M, Zerr I. Upregulation of cellular prion protein (PrPc) after focal cerebral ischemia and influence of lesion severity. Neurosci Lett 2004;372:146−50. 57. Walz R, Amaral OB, Rockenbach IC, Roesler R, Izquierdo I, Cavalheiro EA, et al. Increased sensitivity to seizures in mice lacking cellular prion protein. Epilepsia 1999;40:1679−82.

Kural et al. Evaluation of rat major celluler prion protein (PrPC) for early diagnosis in experimental rat brain trauma model 58. Milhavet O, McMahon HE, Rachidi W, Nishida N, Katamine S, Mangé A, et al. Prion infection impairs the cellular response to oxidative stress. Proc Natl Acad Sci U S A 2000;97:13937−42. 59. Carulla P, Bribián A, Rangel A, Gavín R, Ferrer I, Caelles C, et al. Neuroprotective role of PrPC against kainate-induced epileptic seizures and cell death depends on the modulation of JNK3 activation by GluR6/7PSD-95 binding. Mol Biol Cell 2011;22:3041−54. 60. You H, Tsutsui S, Hameed S, Kannanayakal TJ, Chen L, Xia P, et al. Aβ neurotoxicity depends on interactions between copper ions, prion protein, and N-methyl-D-aspartate receptors. Proc Natl Acad Sci U S A 2012;109:1737−42. 61. Weise J, Sandau R, Schwarting S, Crome O, Wrede A, Schulz-Schaeffer

W, et al. Deletion of cellular prion protein results in reduced Akt activation, enhanced postischemic caspase-3 activation, and exacerbation of ischemic brain injury. Stroke 2006;37:1296−300. 62. Shyu WC, Lin SZ, Chiang MF, Ding DC, Li KW, Chen SF, et al. Overexpression of PrPC by adenovirus-mediated gene targeting reduces ischemic injury in a stroke rat model. J Neurosci 2005;25:8967−77. 63. Spudich A, Frigg R, Kilic E, Kilic U, Oesch B, Raeber A, et al. Aggravation of ischemic brain injury by prion protein deficiency: role of ERK-1/2 and STAT-1. Neurobiol Dis 2005;20:442−9. 64. Hoshino S, Inoue K, Yokoyama T, Kobayashi S, Asakura T, Teramoto A, et al. Prions prevent brain damage after experimental brain injury: a preliminary report. Acta Neurochir Suppl 2003;86:297−9.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Deneysel beyin travması oluşturulan sıçanlarda erken tanı için sellüler prion protein(PrPC)’nin değerlendirilmesi Dr. Alev Kural,1 Dr. Şebnem Tekin Neijmann,1 Dr. Aysun Toker,2 Dr. Halil Doğan,3 Dr. Nurten Sever,4 Dr. Sezgin Sarıkaya5 Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Biyokimya Bölümü, İstanbul Karaman Özel Hastanesi, Biyokimya Kliniği, Karaman Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, İstanbul 4 Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Patoloji Kliniği, İstanbul 5 Yeditepe Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, İstanbul 1 2 3

AMAÇ: Travmatik beyin yaralanması önemli bir problem olmasına rağmen, tanıda yardımcı olan yaygın kullanımlı bir nöro-biyobelirteç yoktur. Bu çalışma, S100B ve prion protein (PrPC) düzeylerini travmatik beyin yaralanması oluşturulan sıçanlarda değerlendirmeyi amaçlamaktadır. GEREÇ VE YÖNTEM: On beş albino cinsi sıçan; sham (1), kontrol (6) ve travma (8) olarak üç gruba ayrıldı. Travmatik beyin yaralanması modifiye serbest düşme modeli ile oluşturuldu. S100B, PrPC düzeyleri ELISA yöntemi ile ölçüldü. Beyin örnekleri patolojik inceleme için çıkarıldı. BULGULAR: Serum S100B ve PrPc düzeyleri travma grubunda, travmadan sonraki 2. ve 24. saatlerde yüksek bulundu (sırasıyla, p<0.002, p<0.002). Ayrıca travma grubundan alınan beyin örneklerinde histopatolojik yaralanma skoru yüksek bulundu. Sadece serum PrPc düzeyleri ile çıkarılan beyin dokusundaki yaralanma skoru arasında pozitif korelasyon vardı (p=0.039, r= 0.731). ROC analizi ile iki parametre incelendiğinde travmatik beyin yaralanmasının tanısında sensitivite ve spesifitesi aynı bulundu. TARTIŞMA: S100B ve PrPc düzeyleri bizim deneysel modelimizde tanıda iyi sensitiviteye sahiplerdi. PrPc travmatik beyin yaralanması ile gelen hastalarda güvenilir bir belirteç olarak kullanılabilir. Bu biyo-belirteçin tanısal değerini gösterecek klinik çalışmalara ihtiyaç vardır. Anahtar sözcükler: S100B; sellüler prion protein (PrPC); travmatik beyin hasarı. Ulus Travma Acil Cerrahi Derg 2020;26(1):1-8

doi: 10.5505/tjtes.2018.46923

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EXPERIMENTAL STUDY

The effects of dexmedetomidine in increased intestinal permeability after traumatic brain injury: An experimental study Onur Karaca, M.D.,1

Güvenç Doğan, M.D.2

Department of Anesthesiology and Reanimation, Aksaray University Faculty of Medicine, Aksaray-Turkey

Department of Anesthesiology and Reanimation, Hitit University Faculty of Medicine, Çorum-Turkey

ABSTRACT BACKGROUND: This study aims to investigate whether or not dexmedetomidine (DEX) application affects inflammation, increased intestinal mucosa damage and intestinal permeability in traumatic brain injury (TBI). METHODS: The rats included in our study were randomized into three groups as the control group (Group 1, n=10), trauma group (Group 2, n=10) and the trauma+dexmedetomidine group (Group 3, n=10). While trauma was not induced in the control group, head trauma was induced in all rats in Groups 2 and 3 with the same method. The rats in Group 3 additionally received the DEX application. Intestinal THF-a, serum TNF-a, IL-6, IL-1b and D-lactate levels were measured six hours post-trauma to assess systemic and local infection. Histopathological evaluation of the terminal ileum was performed at the 6th hour to assess mucosal damage. Intestinal permeability was evaluated by measuring the level of dextran injected into the 5-cm ileum segment adhered to the proximal and distal edges at the 30th minute in the blood taken by cardiac puncture. RESULTS: Intestinal TNF-a (p=0.003), serum TNF-a (p=0.009), IL-6 (p=0.002), IL-1b (p=0.001), and D-lactate levels measured in Group 3 (p=0.046) were significantly lower than those measured in Group 2. Dextran level measured in blood in Group 3 was observed significantly lower than that of Group 2 (p<0.001). Histopathological evaluation of the intestines revealed no injuries in the ileum of the rats in Group 1, injury in the ileum, villus atrophy and mucosal damage in the rats in Group 2, and a significant recovery was observed in Group 3 in comparison to Group 2. CONCLUSION: It was seen in our study that DEX reduced TBI-induced increased inflammation, intestinal mucosa damage and intestinal permeability. These results suggest that DEX may ameliorate the damage done to the intestinal tissue by modulating postTBI inflammatory responses. Keywords: Dexmedetomidine; intestinal mucosa damage; intestinal permeability; traumatic brain injury.

INTRODUCTION Traumatic brain injury (TBI) is the impairment of brain functions due to a blow to the head, penetrating injury, or concussion.[1] Except for conditions, such as neuromotor dysfunction, cognitive disorder and posttraumatic epilepsy, which develop in consequence to tissue damage, systemic physiological impairments, such as autonomic dysfunction, systemic inflammation and organ dysfunction can also occur.[2] Systemic inflammation plays an important role in the

emergence of the gastrointestinal system (GIS) dysfunction seen as a result of traumatic brain injury. It has been reported that an increase in proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL6) and interleukin 1-beta (IL1-b), have a vital role in the process of intestinal damage and the increase in necrosis-dependent intestinal permeability may lead to bacterial translocation and even sepsis. Therefore, treatment modalities aimed at the

Cite this article as: Karaca O, Doğan G. The effects of dexmedetomidine in increased intestinal permeability after traumatic brain injury: An experimental study. Ulus Travma Acil Cerrahi Derg 2020;26:9-14. Address for correspondence: Onur Karaca, M.D. Aksaray Üniversitesi Eğitim ve Araştıma Hastanesi, Anesteziyoloji Anabilim Dalı, 68200 Aksaray, Turkey Tel: +90 382 - 212 91 09 E-mail: asalkaraca@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):9-14 DOI: 10.14744/tjtes.2019.49768 Submitted: 28.08.2019 Accepted: 29.10.2019 Online: 30.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Karaca et al. The effects of dexmedetomidine in increased intestinal permeability after traumatic brain injury

prevention of GIS dysfunction are clinically crucial.[3–6] As a highly selective alpha 2 adrenoceptor agonist, DEX is widely used in intensive care units (ICU) and during surgeries as a sedative and analgesic.[7,8] DEX is a potential agent with known anti-inflammatory and anti-apoptosis effects. [9,10] Moreover, it has been reported in previous studies that DEX significantly reduces serum TNF-a, interleukin 6 (IL-6) and interleukin 1 beta (IL-1b) levels in patients with intestinal damage.[11,12] However, to our knowledge, the effects of DEX on TBI-dependent increased intestinal permeability have never been investigated despite its known anti-inflammatory effects. This study aimed to investigate whether the DEX application affects the increased intestinal mucosa damage and intestinal permeability in TBI.

MATERIALS AND METHODS Animals Ethical approval was obtained from the Experimental Animals Local Ethics Committee of Ankara Training and Research Hospital (date: 01.07.2019, no: 0054). Male Sprague-Dawley rats (280–330 g) were kept in separate cages at 23±2°C with a 12/12 dark/light cycle and fed with standard pellet feed and water. The rats were divided into three groups using a computer randomization procedure as the control group (Group 1) (n=10), trauma group (Group 2) and trauma+dexmedetomidine (Group 3) (n=10). No trauma was induced and medication was administered in Group 1. A cerebral contusion was induced in Groups 2 and 3 to achieve TBI with the method previously described by Bansal et al.[5] All groups were put under anesthesia with 75 mg/kg intraperitoneal ketamine (Ketalar®, Pfizer Pharma GMBH, Germany) and 10 mg/kg xylazine hydrochloride (Alfazyne®, %2, Alfasan International, 3440 AB, Woerden, the Netherlands). The head region of all rats was shaved with an electric razor by securing them in hand. A vertical incision was made on the cranium. Using a surgical drill, a hole 4 mm in diameter was drilled to reveal the durometer 1 mm lateral and posterior to the bregma. Afterwards, a metal ball weighing 250 gr was dropped from a 2 cm height on to the durometer and the incision was closed. After the trauma, intravenous 5 uq/kg/h DEX (Precedex, Dexmedetomidine HCl 200 mg/2 mL) was administered for six hours in Group 3, as applied in previous studies.[9]

Histopathological Evaluation When the abdominal cavity was opened to test intestinal permeability at the end of the sixth hour, samples were taken from the ileum. Intestinal samples were put in a 10% formaldehyde solution for the histological evaluation of the tissues and embedded in paraffin blocks by performing routine histological follow-ups. The sections were applied with periodic acid Schiff (PAS) staining for histopathological examinations. Each terminal ileum section was examined and classified by a blinded histopathologist. 10

Intestinal Permeability (In-vivo Intestinal Permeability Assay) The animals were tested for intestinal permeability six hours after TBI as regards the method previously described.[5] After the application of anesthesia and DEX on all three groups, a midline laparotomy was performed. Following the fixation of the ileum and caecum, the 5-cm terminal ileum segment was isolated. Previously prepared FITC-Dextran (25 mg 4.4 kDa FITC-Dextran in 200 mL PBS) was injected into the lumen of the isolated ileum segment. The intestinal segment removed was put back into the abdominal cavity, and the abdominal wall was closed with 3.0 silk. Thirty minutes following injection, blood was taken with the cardiac puncture. Blood samples were put inside heparinized Eppendorf tubes and centrifuged at 10.000 g for ten minutes. After the separation of the plasma part, the test was completed using a SpectraMax M5 fluorescent spectrophotometer (Molecular Devices, Sunnyvale, CA) to determine FITC-Dextran concentration.

Intestinal TNF-a Measurement Protein was extracted from the terminal ileum by homogenizing the tissue in 500 mL of ice-cold tissue protein extraction reagent (T-PER) containing 1% protease inhibitor and 1% phosphatase inhibitor (Pierce Biotechnology). Homogenates were centrifuged at 10,000 g for 5min. The supernatant was obtained and stored at -708C. Intestinal TNF-a was measured in Groups 2 and 3 using a commercially available ELISA assay (R&D system, Minneapolis, MN). Values were reported as pg/mL.

Blood TNF-a, IL-6, IL-1B Measurement Commercially available ELISA kits were used to measure the levels of TNF-a, IL-6 and IL-1b (R&D System, Minneapolis, Minn) utilizing a SpectraMax M2e Microplate Spectrophotometer (Bio-RAD, Berkeley, CA) as instructed by the manufacturer. Six hours after the DEX application, the test was performed taking blood from the intraabdominal aorta when the abdominal cavity as opened for dextran testing.

D-Lactate Measurement Plasma D-lactate levels were measured using a D-lactate Colorimetric Test Kit (BioVision, Milpitas, CA) as instructed by the manufacturer. Test samples were prepared in a 96-gouged plate with test tampons and mixed with the reaction mixture for 30 minutes at room temperature. Optic density was measured at 450 nm. A series of D-lactate standard solutions was diluted and the standard curve was given, and hence the concentration of the samples was measured.

Statistical Methods Statistical analyses were conducted using SPSS (Version 22.0, SPSS Inc., Chicago, IL, USA). Descriptive statistics were presented as mean±standard deviation values. Distributions of the data were evaluated using Shapiro-Wilk tests. Homogeneity of variance was evaluated by the Levene test. The significance of Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Karaca et al. The effects of dexmedetomidine in increased intestinal permeability after traumatic brain injury

Table 1. Comparison of intestinal TNF-α, TNF-α, IL-6, IL-1B, Dextran and D-lactate according to rat groups

Groups

Mean±SD

P-values

Intestinal

TBI

8 44.00±8.78 0.003a –

TNF-α (pg/mL)

TBI + DEX

29.50±6.90

TNF-α (pg/mL)

Sham

1.70±0.45

TBI

3.63±0.61

TBI + DEX

2.72±0.25

2–3: 0.009

IL-6 (pg/mL)

Sham

1.62±1.06

1–2: <0.001

TBI

52.62±13.60

TBI + DEX

25.62±11.50

<0.001b

Post-hoc P-values

1–2: <0.001 1–3: 0.001

<0.001b

1–3: 0.001 2–3: 0.002

IL-1B (pg/mL)

Sham

2.23±0.92

TBI

11.08±2.67

<0.001

TBI + DEX

4.96±0.89

2–3: 0.001

Dextran (ug/mL)

Sham

18.81±2.64

1–2: <0.001

TBI

68.71±16.33

1–3: 0.002

TBI + DEX

25.02±7.09

2–3: <0.001

D-Lactate (mmol/L)

Sham

0.65±0.15

1–2: <0.001

TBI

1.10±0.25

1–3: 0.109

TBI + DEX

0.85±0.13

2–3: 0.046

1–2: <0.001

1–3: <0.001

<0.001b

0.001c

a Student’s t-test. bANOVA with Games-Howell post hoc test. cANOVA with Tukey HSD post hoc test. TBI: Traumatic brain injury; DEX: Dexmedetomidine; TNF-a: tumor necrosis factor-alpha; IL-6: Interleukin-6; IL-1B: Interleukin 1-beta; SD: Standard deviation.

the difference between more than two groups was evaluated using the one-way ANOVA test since data met the assumptions of normality. Post-hoc tests with Tukey HSD or GamesHowell were used to determine which groups differed with pairwise comparison according to the homogeneity of the variances. A value of p<0.05 was considered statistically significant.

RESULTS Statistical comparisons of intestinal TNF-α, TNF-α, IL-6, IL-

1B, Dextran and D-lactate by rat groups are given in Table 1. There was a statistically significant difference between the rat groups concerning intestinal TNF-α (pg/mL), TNF-α (pg/mL), IL-6 (pg/mL), IL-1B (pg/mL), Dextran (ug/mL) and D-Lactate (mmol/L) parameters (Table 1). There was a difference between all groups according to the results of the Post hoc test (Table 1). Boxplots for comparison of intestinal Dextran, D-lactate, TNF-α, TNF-α, IL-6, and IL-1B according to rat groups are shown in Figure 1 and 2.

100.00 1.50

D-Lactate (mmol/L

Dextran ug/mL

80.00

60.00

40.00

1.25

1.00

.75

20.00 .50 .00 Sham

TBI

TBI + DEX

Groups

Sham

TBI

TBI + DEX

Groups

Figure 1. Boxplot for comparison of Dextran and D-lactate by rat groups.

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Karaca et al. The effects of dexmedetomidine in increased intestinal permeability after traumatic brain injury

5.00

50.00

4.00 TNF-a (pg/mL)

Intestinal TNF-a (pg/mL)

60.00

40.00

30.00

3.00

2.00

20.00

1.00

10.00 TBI

TBI + DEX

Sham

TBI

TBI + DEX

TBI

TBI + DEX

14.00 12.00 10.00

IL-1B (pg/mL)

IL-6 (pg/mL)

60.00

40.00

20.00

8.00 6.00 4.00 2.00 .00

10.00 Sham

TBI

TBI + DEX

Sham

Groups

Figure 2. Boxplot for comparison of intestinal TNF-Îą, TNF-Îą, IL-6, and IL-1B by rat groups.

Histopathological Findings Images in intestinal tissues are presented in Figures 3, 4 and 5.

DISCUSSION

effects of the DEX on post-TBI intestinal damage and permeability. We put forth with this study that DEX, which is widely used in intensive care and anesthetic applications, has curative effects on post-TBI systemic inflammation, increased

To our knowledge, our study is the first investigating the

intestinal permeability and intestinal mucosa.

Figure 3. Histological section of group 1 ileum. Undamaged single columnar epithelial cells and (arrows) apical region shows a brush border. (arrowheads) goblet cells (400x).

Figure 4. Histological section of group 2 ileum. General damaged single columnar epithelial cells and (arrows) brush border (arrowheads) goblet cells (400x).

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Karaca et al. The effects of dexmedetomidine in increased intestinal permeability after traumatic brain injury

It is to our belief that this improvement was realized by the anti-inflammatory effects of DEX.

Figure 5. Histological section of group 3 ileum. Partial damaged single columnar epithelial cells and (arrows) brush border (arrowheads) goblet cells (400x).

Previous studies have concluded that D-lactate shows the severity of the intestinal damage and also changes consistently with the epithelial function of the intestinal barrier are among microbiota metabolites.[13] In this study, we found serum D-lactate levels in Group 3 significantly lower than those in Group 2, which provided us with important evidence that the intestinal mucosa barrier was protected as regards the trauma group. Studies in the literature show an immediate increase in the level of proinflammatory cytokines (TNF-a, IL-1, IL-6, IL-12) after TBI.[4,14,15] Again, Tamion et al.[16] have reported that the increase in inflammatory cytokines, such as TNF-a, IL-1Î˛ and IL-6, plays an important role in the intestinal damage process. By activating systemic inflammatory response together with the endotoxins in circulation, the intestinal immune system may cause multiple organ failure. Many studies have demonstrated that systemic inflammatory cytokines are correlated to intestinal damage.[17,18] In this study, a significant increase was observed in the systemic inflammatory cytokines (TNF-a, IL-6, IL-1B) of the trauma group, which in turn expressed that systemic inflammatory response may lead to intestinal damage. Previous studies on TBI have determined that intestinal permeability that develops due to systemic and local inflammation is a problem leading to serious life-threatening complications like sepsis in critical patients.[6] Severe damage may occur in the intestinal structure after TBI. Thus, its barrier function is destroyed. The deterioration of the intestinal integrity starts at as early as the third hour of brain injury and specifically results in mucosal atrophy on the seventh day. Morphological changes, such as mucosal atrophy on the intestinal mucosa, destruction of binding proteins between epithelial cells, villus loss, focal ulcerations, neighboring villus fusion, villus interstitium and edema in lamina propria, can be seen. This deep mucosal damage causing the anatomical deterioration of the intestinal barrier leads to an increase in intestinal permeability in the end.[19] In this study, we histologically ensured amelioration and significant improvement in the villus structure in Group 3 in comparison to Group 2. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Chen et al.[9] have emphasized that DEX improves intestinal damage by reducing systemic inflammation. Furthermore, previous studies have shown that DEX inhibits the expression of inflammatory mediators containing NO, prostaglandin E2, TNF-a and IL-6.[20] Previously conducted studies on rats have found that the use of the DEX leads to a decrease in the expression of TNF-a in ischemic hippocampal tissue and in the TNF-a and IL-6 concentrations in rats exposed to endotoxins.[21,22] Again, Kayhan et al.[23] have shown the immunomodulatory effects and suppressive effects of DEX on proinflammatory cytokines in a colitis model they have generated. As a result of finding low levels of cytokine in our rat model that received DEX, we suggested that DEX suppressed systemic inflammation, which in turn provided us with evidence indicating that DEX may ameliorate intestinal mucosa damage by preventing systemic inflammation of the intestinal damage. Limitations to our study include that previous studies have mentioned that DEX has curative effects in ischemia-reperfusion damage and surgery-related stress response on the intestinal tissue by increasing intestinal blood flow.[24] We could not evaluate this parameter since we lacked the facilities to show the microcirculation of the intestinal tissue after the DEX application. Again, we failed to examine the status of the intestinal mucosal interties since we did not have the means to examine the intestinal tissue immunohistochemically. These results have provided data on the curative effects s of DEX on the intestinal tissue by modulating inflammatory responses after TBI.

Conclusion In conclusion, we observed that DEX ameliorated TBI-induced systemic inflammation and increased intestinal permeability. We believe that further studies are needed for DEX, which is a mediator to the protection of intestinal tissue post-TBI.

Acknowledgment We thank Ercan Ayaz from the Histology and Embryology Department for assistance with our histological evaluation. In addition, we want to thank Yasin KenesarÄą from the Department of Medical Biochemistry for assistance with our biochemistry evaluation. Finally, we want to thank Emre Demir from the Department of Biostatistics for statistical analysis assistance. Ethics Committee Approval: Approved by the local ethics committee (date: 01.07.2019, no: 0054). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: O.K., G.D.; Design: O.K., G.D.; Supervision: O.K., G.D.; Fundings: O.K., G.D.; Materials: O.K., G.D.; Data: O.K., G.D.; Analysis: O.K., G.D.; Literature search: O.K., G.D.; Writing: O.K., G.D.; Critical revision: O.K., G.D. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support. 13

Karaca et al. The effects of dexmedetomidine in increased intestinal permeability after traumatic brain injury

REFERENCES 1. Dilmen ÖK, Akçıl EF, Tunalı Y. Intensive Care Treatment in Traumatic Brain Injury. Turk J Anaesthesiol Reanim 2015;43:1−6. 2. Baguley IJ, Heriseanu RE, Cameron ID, Nott MT, Slewa-Younan S. A critical review of the pathophysiology of dysautonomia following traumatic brain injury. Neurocrit Care 2008;8:293–300. 3. Cook AM, Peppard A, Magnuson B. Nutrition considerations in traumatic brain injury. Nutr Clin Pract 2008;23:608−20. 4. Kemp CD, Johnson JC, Riordan WP, Cotton BA. How we die: the impact of nonneurologic organ dysfunction after severe traumatic brain injury. Am Surg 2008;74:866−72. 5. Bansal V, Costantini T, Kroll L, Peterson C, Loomis W, Eliceiri B, et al. Traumatic brain injury and intestinal dysfunction: uncovering the neuroenteric axis. J Neurotrauma 2009;26:1353−9. 6. Feighery L, Smyth A, Keely S, Baird AW, O’Connor WT, Callanan JJ, et al. Increased intestinal permeability in rats subjected to traumatic frontal lobe percussion brain injury. J Trauma 2008;64:131−7. 7. Brandão PG, Lobo FR, Ramin SL, Sakr Y, Machado MN, Lobo SM. Dexmedetomidine as an Anesthetic Adjuvant in Cardiac Surgery: a Cohort Study. Braz J Cardiovasc Surg 2016;31:213−8. 8. Venn RM, Bradshaw CJ, Spencer R, Brealey D, Caudwell E, Naughton C, et al. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia 1999;54:1136−42. 9. Chen Y, Miao L, Yao Y, Wu W, Wu X, Gong C, et al. Dexmedetomidine Ameliorate CLP-Induced Rat Intestinal Injury via Inhibition of Inflammation. Mediators Inflamm 2015;2015:918361. 10. Taniguchi T, Kidani Y, Kanakura H, Takemoto Y, Yamamoto K. Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats. Crit Care Med 2004;32:1322−6. 11. Li B, Li Y, Tian S, Wang H, Wu H, Zhang A, et al. Anti-inflammatory Effects of Perioperative Dexmedetomidine Administered as an Adjunct to General Anesthesia: A Meta-analysis. Sci Rep 2015;5:12342. 12. Memiş D, Hekimoğlu S, Vatan I, Yandim T, Yüksel M, Süt N. Effects of midazolam and dexmedetomidine on inflammatory responses and gastric intramucosal pH to sepsis, in critically ill patients. Br J Anaesth

2007;98:550−2. 13. Lorenz I, Vogt S. Investigations on the association of D- lactate blood concentrations with the outcome of therapy of acidosis, and with posture and demeanour in young calves with diarrhea. J Vet Med A 2006;53:490−4. 14. Hang CH, Shi JX, Li JS, Li WQ, Wu W. Expressions of intestinal NFkappaB, TNF-alpha, and IL-6 following traumatic brain injury in rats. J Surg Res 2005;123:188−93. 15. Lenz A, Franklin GA, Cheadle WG. Systemic inflammation after trauma. Injury 2007;38:1336−45. 16. Tamion F, Richard V, Lacoume Y, Thuillez C. Intestinal preconditioning prevents systemic inflammatory response in hemorrhagic shock. Role of HO-1. Am J Physiol Gastrointest Liver Physiol 2002;283:G408−14. 17. Doğan G, İpek H, Baş Y, Doğan G, Kayır S. Experimental study on prophylactic effects of vardenafil in ischemia-reperfusion model with intestinal volvulus injury in rats. J Pediatr Surg 2019;54:2172−7. 18. Özkan N, Ersoy ÖF, Özsoy Z, Çakır E. Melatonin exhibits supportive effects on oxidants and anastomotic healing during intestinal ischemia/ reperfusion injury. Ulus Travma Acil Cerrahi Derg 2018;24:1−8. 19. Hang CH, Shi JX, Li JS, Wu W, Yin HX. Alterations of intestinal mucosa structure and barrier function following traumatic brain injury in rats. World J Gastroenterol 2003;9:2776−81. 20. Lin CY, Tsai PS, Hung YC, Huang CJ. L-type calcium channels are involved in mediating the anti-inflammatory effects of magnesium sulphate. Br J Anaesth 2010;104:44−51. 21. Eser O, Fidan H, Sahin O, Cosar M, Yaman M, Mollaoglu H, et al. The influence of dexmedetomidine on ischemic rat hippocampus. Brain Res 2008;1218:250−6. 22. Taniguchi T, Kurita A, Kobayashi K, Yamamoto K, Inaba H. Dose- and time-related effects of dexmedetomidine on mortality and inflammatory responses to endotoxin-induced shock in rats. J Anesth 2008;22:221−8. 23. Erdogan Kayhan G, Gul M, Kayhan B, Gedik E, Ozgul U, Kurtoglu EL, et al. Dexmedetomidine ameliorates TNBS-induced colitis by inducing immunomodulator effect. J Surg Res 2013;183:733−41. 24. Sun Y, Gao Q, Wu N, LI SD, Yao JX, Fan WJ. Protective effects of dexmedetomidine on intestinal ischemia reperfusion injury. Exp Ther Med 2015;10:647−52.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Travmatik beyin hasarında artmış bağırsak geçirgenliğine deksmedetomidinin etkisi: Deneysel çalışma Dr. Onur Karaca,1 Dr. Güvenç Doğan2 1 2

Aksaray Üniversitesi Tıp Fakültesi, Anestezi ve Reanimasyon Anabilim Dalı, Aksaray Hitit Üniversitesi Tıp Fakültesi, Anestezi ve Reanimasyon Anabilim Dalı, Çorum

AMAÇ: Deksmedetomidin (DEX) uygulamasının travmatik beyin hasarında (TBH) enflamasyonu, artan bağırsak mukoza hasarını ve bağırsak geçirgenliğini etkileme durumu araştırıldı. GEREÇ VE YÖNTEM: Çalışmamızda değerlendirdiğimiz hayvanlar kontrol grubu (Grup 1, n=10), travma grubu (Grup 2, n=10) ve travma + deksmetetomdin grubu (Grup 3, n=10) olmak üzere üç gruba randomize edildi. Kontrol grubuna travma uygulanmazken, Grup 2 ve 3’deki sıçanların hepsine aynı yöntemle kafa travması uygulandı. Grup 3’deki sıçanlara ek olarak intraperitoneal DEX uygulaması yapıldı. Sistemik ve lokal enflamasyonu değerlendirmek için travmadan 6 saat sonra bağırsak TNF-a, serum TNF-a, IL-6, IL-1b, D-laktat düzeyleri ölçüldü. Mukoza hasarını değerlendirmek için 6. saatte terminal ileumun histopatolojik incelemesi yapıldı. İntestinal geçirgenliği değerlendirmek için ise proksimal ve distal uçlarından bağlanan 5 cm’lik ileum segmentine enjekte edilen dekstranın 30. dakikada kardiyak ponksiyonla alınan kandaki düzeyi ölçüldü. BULGULAR: Grup 3’te ölçülen bağırsak TNF-a (p=0.003), serum TNF-a (p=0.009), IL-6 (p=0.002), IL-1b (p=0.001), D-laktat düzeyleri (p=0.046), Grup 2’ye göre anlamlı ölçüde düşük saptandı. Grup 3’te kanda ölçülen dekstran düzeyi Grup 2’ye göre anlamlı düzeyde düşük gözlendi (p<0.001). Bağırsakların histopatolojik incelemesinde ise; Grup 1’deki sıçanların ileumunda hasar yok, Grup 2’deki sıçanların ileumunda; villus atrofisi ve mukozal hasar, Grup 3’dekilerin ise Grup 2’ye göre anlamlı derecede iyileşme olduğu gözlendi. TARTIŞMA: Çalışmamızda DEX’in TBI kaynaklı artan enflamasyonu, bağırsak mukoza hasarını ve bağırsak geçirgenliğini azalttığı görüldü. Bu sonuçlar, DEX’in, TBH sonrası enflamatuvar yanıtları modüle ederek bağırsak dokusuna verilen hasarı iyileştirebileceğini göstermiştir. Anahtar sözcükler: Bağırsak mukoza hasarı; deksmedetomidin; intestinal geçirgenlik; travmatik beyin hasarı. Ulus Travma Acil Cerrahi Derg 2020;26(1):9-14

doi: 10.14744/tjtes.2019.49768

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

EXPERIMENTAL STUDY

The importance of preliminary evaluation in developing ambulance staff training curriculum for developing countries: A survey in Uzbekistan Woo Chan Jeon, M.D.,1 Hyun Jong Kim, M.D.,1 Junseok Park, M.D.,1 Kyung Hwan Kim, M.D.,1 Dong Wun Shin, M.D.,1 Joon Min Park, M.D.,1 Jung Eon Kim, M.D.,1 Ji Sook Lee, M.D.,2 Hoon Kim, M.D.1 1

Department of Emergency Medicine, Inje University, Ilsan Paik Hospital, Goyang-Korea

Department of Emergency Medicine, Ajou University, School of Medicine, Suwon-Korea

ABSTRACT BACKGROUND: The Tashkent city, the capital of the republic of Uzbekistan, started joint project with Korean emergency physicians to improve the quality of their ambulance services in 2016. Ambulance service in Tashkent city has been facing challenges in processing a large number of calls, and low competency of their staff in providing advanced prehospital emergency care. To design an appropriate capacity building training program for ambulance staff, we analyzed the current ambulance service in Tashkent concerning resources and competency of the staff. METHODS: In this study, ambulance staff participated in the constructed survey and pre-validated written test. Statistics and other information were provided by the Ministry of Health of Uzbekistan. RESULTS: Ninety-eight ambulance staff were participated in this study, and more than half (53.1%) of the participants were physicians. The average years of service in the ambulance were 8.71Âą6.9 years. In the ambulance, drugs were stocked in enough quantity include injections for critical care, except large volume fluids for resuscitation. Only 19 to 52 percent of the ambulances were equipped with essential monitoring devices. Competency for the basic procedure was surveyed higher than 60%, but critical care skills, such as defibrillation, were as low as 18%. The written test resulted in only 41.1% correct answer rate, though it was higher than 60% in the validation test for Korean ambulance staff. Conventional prehospital knowledge and skillset deemed to be essential for ambulance staff were found to be marginal in the test. CONCLUSION: The ambulance staff in Tashkent, Uzbekistan found to have insufficient medical knowledge and clinical decisionmaking abilities. Training program for ambulance staff in Tashkent should be developed on the basis of the findings in this study. Keywords: Capacity building; emergency medical services; self-evaluation programs; Uzbekistan.

INTRODUCTION In the 20th century, public health policy of low and middle-income countries mainly emphasized maternal care and control of communicable diseases.[1] However, the focus has shifted to non-communicable diseases, such as ischemic heart disease, stroke, and road injury, have become the major causes of death in low and middle-income countries.[2] Hence, many

reports have recommended developing and reinforcing the emergency medical services (EMS) in low middle-income countries.[3,4] Given that the development and reinforcement of EMS require a considerable amount of human resources, and financial supports, foreign aid projects play an important role in meeting the needs through developing EMS algorithm and EMS staff training program in low middle-income countries.[3]

Cite this article as: Jeon WC, Kim HJ, Park J, Kim KH, Shin DW, Park JM, et al. The importance of preliminary evaluation in developing ambulance staff training curriculum for developing countries: A survey in Uzbekistan. Ulus Travma Acil Cerrahi Derg 2020;26:15-20. Address for correspondence: Hoon Kim, M.D. 2240 Daehwa-dong, Ilsan Seo-gu, Goyang-si, Gyeonggi-do, Korea 10380 Goyang-si - South Korea Tel: +82-31-910-9782 E-mail: megali@hanmail.net Ulus Travma Acil Cerrahi Derg 2020;26(1):15-20 DOI: 10.14744/tjtes.2019.79595 Submitted: 13.10.2018 Accepted: 11.03.2019 Online: 27.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Jeon et al. The importance of preliminary evaluation in developing ambulance staff training curriculum for developing countries

From January to April 2016, in cooperation with the Ministry of Health of Uzbekistan, the team of emergency physicians from Korea analyzed the status of the emergency medical system in Tashkent, the capital of Uzbekistan, and confirmed the feasibility of the EMS reinforcement project. The objective of this project is to contribute to the improvement of the emergency medical care system quality, enhancement of hospital operation efficiency, and the strengthening of the public medical system in Uzbekistan through practical and efficient capacity building program for pre-hospital emergency medical staff working in Tashkent. The project included the development and operation of the emergency medical personnel capacity building program. In Tashkent, the ambulance staff is comprised of various healthcare workers, such as general physicians, feldshers, and nurses. The education system of the ambulance staff is as follows: general physicians should have completed three years of college or lyceum (such as vocational-technical school) and seven years of the medical school curriculum. The general physicians must also have passed the written and oral tests for a license. Feldshers, who are health care personnel that provide medical services limited to emergency treatment and ambulance service, provide primary, obstetric and surgical care in Uzbekistan. Training for feldshers includes up to four years of post-secondary education, including knowledge and skill for diagnosis and treatment.[5] The curricula for nurses consist of three years of college or lyceum with an extension of two or three years for nursing education in medical high school. To become an ambulance staff, the general physician, feldsher and nurse should complete an additional one-year course of postgraduate education.[6] In Tashkent, 140 ambulances were identified as operational with 1,642 staff in 2016. The ambulance staff had two roles in Tashkent. First, when the patient’s condition is deemed to be non-emergent, the ambulance staff act as a visiting primary physician and provide on-scene primary care without transportation to the hospital. Second, if the patient’s condition is determined to be emergent, the ambulance staff is responsible for the transportation of the patient to the designated emergency facilities. Since ambulance service is free public service in Tashkent, many people use it when they need medical attention, even with minor symptoms. Frequently, available resources are diverted to primary medical care, raising concern for endangering emergent cases. Researchers have described the importance of enhancing the capacities of ambulance staff in implementing on-scene triage and proper management of the emergent patient.[6] To this end, we performed the preliminary evaluation of emergency medical staff for developing a training program. This project aimed to help the development of EMS training program in low middle-income countries by introducing preliminary evaluation about the medical equipment in ambulances, medical knowledge in dealing with emergencies, and the clinical decision-making process of ambulance staff in Uzbekistan. 16

MATERIALS AND METHODS In cooperation with the Ministry of Health of Uzbekistan, we collected data about the staff working at an ambulance station in Tashkent city as ambulance staff, dispatcher, or medical director. A survey was conducted to identify the personal data, emergency medical equipment and clinical experiences of the related personnel. A written test was formulated to evaluate medical knowledge and clinical decision-making skills (Appendix A). Both the survey sheet and written test were translated into the Russian language and distributed to the participants. This study was reviewed and approved by the Institutional Review Board of Inje University, Ilsan Paik Hospital. Informed consent was waived by the board. The survey sheet contained demographics of participants, type of certification, durations of clinical experience, recent education opportunity and the role in the EMS to grasp the general characteristics of the participants. The medical equipment in the ambulance was also surveyed. First, the list of medical equipment in the ambulance was reviewed and categorized, and then, a questionnaire regarding the functionality of medical equipment in the ambulance was filled out. Items included intravenous medicines and fluids as well as medical device assisting emergency management and monitoring of the patients. The participants also asked to judge their own clinical performance related to competency, experience and confidence. The survey about clinical performance consisted of three contents. One is related to clinical performance assisting the airway and breathing of patients and the other two are clinical performance assisting circulation of patients and trauma management, such as cervical immobilization. Researchers developed the written test on the basis of education programs, such as Basic Life Support, Advanced Cardiac Life Support, Advanced Trauma Life Support and Neonatal Resuscitation Program.[7–10] This test was first validated in more than 100 ambulance staff in Korea, who are certified EMT (Emergency Medical Technician), with an average score higher than 60 percent. The test consisted of 32 questions in total; airway and oxygen therapy (four questions), basic cardiopulmonary resuscitation (four questions), electrocardiogram (eight questions), advanced cardiopulmonary resuscitation (eight questions), prehospital trauma assessment and management (four questions) and neonatal resuscitation (four questions).

RESULTS General Characteristics of the Participants Ninety-eight emergency medical staff participated in this study. There were 73 male and 25 female participants. The average age was 34.68±8.71 years old. The certification type of participants was 52 physicians (53.1%), 42 feldshers (42.8%), and three nurses (3.1%). The average training hours they attended in recent two years was 171.4 hours. The composition of the clinical experience of participants was as follows. Ambulance boarding was 74%, general hospital working was 15%, outpaUlus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Jeon et al. The importance of preliminary evaluation in developing ambulance staff training curriculum for developing countries

Table 1. General characteristics of the participants

Frequency (%)

Age

Years

Table 2. Medicines, fluids and medical equipment of ambulance in Tashkent, Uzbekistan Intravenous Status Medical Status medicines (%) equipment (%)

34.68±8.71 (20–59)

Sex

Epinephrine

93.9

Suction device

50.0

Male

73 (74.5)

Atropine

93.9

Oxygen generator

44.9

Female

25 (25.5)

Amiodarone

5.1 Laryngoscope 19.4

Lidocaine

98.0 Bag-mask 58.2

52 (53.1)

Digoxin

5.96

42 (42.8)

Droperidol

60.2

Nasal cannula (O2) 7.1

3 (3.1)

Diazepam

16.3

Face mask (O2) 24.5

History of clinical

Calcium gluconate

91.8

experiences

Nifedipine

37.8 Ventilator 31.6

Location

Morphine

96.9

ECG monitor

60.2

8.71±6.9 (1–32)

Verapamil

96.9

Sat O2 monitor

31.6

Nitroglycerin 85.7 Splint 77.6

Medical certification

General physician

Feldsher

Nurse

Ambulance

90 (73.7)

IV line set

32.7

Defibrillator

60.2

General hospital

18 (14.8)

8.39±7.03 (1–22)

OPD/community hospital

11 (9.0)

7.04±6.00 (1–20)

Heparin

73.5

Intravenous fluids

Status

1.67±0.94 (1–3)

Furosemide

96.9

Normal saline

66.3

Prednisolone

96.9

10% DW

17.3

Dextrose

98.0

5% DW

41.8

MgSo4

96.9

50% DW

59.2

Drotaverine

78.6

Half saline

15.3

100 90 80 70 60 50

98% 87%

63%

fa si ce ng m su as ct k io em n ov de e vi F/ ce B in U ai si rw ng ay O PA o H rN ea PA d til tc hi n lif t Ja R w ec th or ru ve st ry Ba po g si m tio as n k ve Tr nt ac ila he tio U a n si li ng nt N ub al ed te at dl r i o n K e n at ee de iv pi e co ng ai m rw su pr ay es rg ic si al on ai in rw pn ay eu C m lo ot se ho d r th ax or ac os to m y

22%

ito

37% 23%

on m

lc an

a ly

na a vi

ly pp

29%

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

yi hg

Figure 1. Clinical performance related to airway and breathing supports. F/B: Foreign Body; OPA: Oropharyngeal airway; NPA: Nasopharyngeal airway.

The participants answered that the experience and confidence of skills related to basic airway management, such as oxygen supply, airway maneuvers and bag-mask ventilation, were over 60 percent (Fig. 1). However, the experience and

Clinical Performances of the Participants

0 sa tu r

77%

57% 38%

86% 85%

77%

75%

68%

The ambulances in Tashkent had various kinds of intravenous medicines, according to the survey. The list provided by the Uzbek side was compared with answers from participants to check the availability of each item. The cardiovascular drugs were epinephrine, atropine, amiodarone, lidocaine, digoxin, calcium gluconate; furosemide and antihypertensive (Table 2) More than 90% of the drugs were in stock in the ambulances, except for amiodarone (Table 2). Drugs other than the cardiovascular drugs included steroids, opioids, benzodiazepine and NSAIDs with some differences in each ambulance. Although the medical devices assisting emergency management and monitoring of the patients are essential, only 19 to 52 percent of the ambulances were equipped with the essential devices. There was a basic prehospital intravenous fluid, such as normal saline and dextrose, in about 60 percent of ambulances, but the volume of the intravenous fluid pack was as small as 100 to 200 mL (Table 2).

Medical Equipment in the Ambulance

confidence level related to techniques related to advanced airway and breathing support like endotracheal intubation, surgical airway and needle decompression were as low as 22 to 38 percent (Fig. 1). In circulation support, more than 80 percent of the participants had the experience and confidence in measuring blood pressure and heart rate, establishing intravenous access, fluid infusion, and drug injection (Fig.

tient or community hospital practice was 9%, and dispatcher in EMS was 9%. The average years of service in EMS were 8.71±6.9 years for the ambulance, 8.39±7.03 years for general hospital, 7.04±6.00 years for outpatient or community hospital, and 1.67±0.94 years for the dispatcher (Table 1).

OPD: Outpatient department.

3 (2.5)

Dispatcher

Jeon et al. The importance of preliminary evaluation in developing ambulance staff training curriculum for developing countries

confidence in basic trauma management like bleeding control wound dressing and applying splints were relatively high at 60 to 97 percent (Fig. 3).

100 90 80 70

Medical Knowledge and Clinical Decision

60 %

97%

95%

89%

81%

88%

62%

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on ca rd io ve rs i

dr ug IV ng

DISCUSSION

U si

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ac c IO

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ea su re

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an d

ac c

es s

H R

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20%

17%

an d

95%

91%

76%

65%

89%

81%

65%

n io

ct du

ct in

in U

sp ng si

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at ig

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ur ct

ou tw es io

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em rh

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to y lb ro nt

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m tre

es pr ct re

di y lb ro nt

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di ee Bl

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ob m m li ca vi er C

97%

91%

32%

Figure 2. Clinical performances related to circulation support. BP: Blood pressure; HR: Heart rate; IO: Intraosseous; IV: Intravenous. 100 90 80 70 60 50 40 30 20 10 0

Figure 3. Clinical performance related to pre-hospital trauma care. 100 90 80 70

60 50 40 30 20

51%

45%

38%

35%

37%

n tio es us ci ta lr ta na

ho sp m ita an l tr ag au em m en a t

Pr e

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ay Ai rw

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10 0

Figure 4. Correct answer rate of written test about medical knowledge and clinical decision.

2). However, only 18â&#x20AC;&#x201C;20 percent of the participants had experience and confidence in using defibrillator and cardioversion critical in cardiopulmonary resuscitation. Experience and 18

The average rate of the correct answer in written test was only 41.1%. In questions related to the airway and oxygen therapy section, advanced cardiopulmonary resuscitation section and prehospital trauma section, only 38, 35 and 38 percent of participants selected correct answers, respectively. In the questions on basic cardiopulmonary resuscitation section, electrocardiogram section and neonatal resuscitation section, 45, 51 and 46 percent of participants selected the correct answers, respectively (Fig. 4).

The ambulance in Tashkent, Uzbekistan had enough intravenous medication for emergency treatment. However, the medical device assisting emergency management and monitoring the condition of patients was insufficient, which may jeopardize the use of the available intravenous medicines in the field. Although there are basic intravenous fluids, such as normal saline and dextrose in the ambulance, the volume of fluid is only 100 to 200 mL, which is not suitable for use in emergency situations.[11] Therefore, developing the education course on the use of patient monitoring devices as well as on intravenous medicines provided in the ambulance was deemed essential.[12] Also, national and institutional support should be placed to simplify the type of intravenous medicines that can be used in the ambulance, and to equip the ambulance with the patient monitoring system, and increase the volume of the intravenous fluid pack. In most developed countries, including the United States, paramedics and emergency medical technicians play an important role in the emergency medical system. Although there are some differences in each country, most countries have a standardized education curriculum and certification system. Ambulance staff is healthcare professionals who respond to medical emergencies outside of a hospital and can not only transfer patients to the hospital but also perform invasive techniques, such as endotracheal intubation and chest compression on-site or during the transportation.[13,14] According to the medical education curriculum in Uzbekistan, most ambulance staff in Tashkent (general physicians and feldshers) has already completed the education course about pre-hospital care, including critical care for severe patients. However, our written test revealed that knowledge, skills, and confidence in their clinical decision relevant to prehospital care were suboptimal. In the assessment of medical knowledge and clinical decision of ambulance staff, in the airway and oxygen, advanced cardiopulmonary resuscitation, and prehospital trauma sections, above 60 percent of the participants chose the improper diUlus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Jeon et al. The importance of preliminary evaluation in developing ambulance staff training curriculum for developing countries

agnosis or wrong clinical decision. Hence, only half of the participants chose the proper diagnosis and clinical decision in the questions on basic cardiopulmonary resuscitation section, electrocardiogram section and neonatal resuscitation section. These results indicate that the ambulance staff in Tashkent is having difficulties in making appropriate judgments and clinical decisions in most emergency situations. Therefore, the researchers decided to develop the training program focused on basic principles of prehospital medical care. Program shall include airway management and breathing support, recognition of arrest, chest compression, interpretations of electrocardiogram and drug choice in cardiac arrhythmia. Considering that Korean EMT, who are only degree holders, scored better than Uzbek ambulance staff with the same test, reasons for lower competency should be analyzed and measures should be developed to enhance their capacity. The ambulance staff in Tashkent also had insufficient clinical experience in advanced procedures. High confidence and experience in the basic techniques, such as oxygen supply, airway maneuvers, bag-mask ventilation, establishing intravenous access and drugs injection, the low confidence and experience of advanced technique, such as tracheal intubation, surgical airway, needle decompression, defibrillator and cardioversion, is probably due to the lack of practical training in the medical education curriculum and the lack of medical equipment in the field. Therefore, practice-based education program should be developed to increase the clinical experiences of ambulance staff in the field or the hospital. The development of practice-based program will require workshops or simulation session about the support of airway, breathing and circulation because ambulance staff had the lack of such clinical experiences. Moreover, scenario - based simulation education will be suitable to improve not only the clinical decisions but also clinical performance. The present study aims to evaluate the medical knowledge and capability to make clinical decision and survey the clinical experiences and medical equipment in ambulances to develop training programs for ambulance staff in Tashkent, Uzbekistan. Considering that the role of ambulance staff is supposed to manage emergencies on scene and to rapidly transfer patients rather than be primary physicians, the program should include basic to advanced prehospital care. This study may be used as a reference to develop the training program of ambulance staff in not only Uzbekistan but also in the countries of the former Soviet Union and other developing countries with similar EMS system. This study has some limitations. First, the researchers recruited the participants with the help of the Ministry of the Health of Uzbekistan. The participants could not represent the characteristics of all ambulance staff in Uzbekistan. Second, this research did not consider the differences in the education curriculum and the emergency medical system between Uzbekistan and Korea. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Conclusion The ambulance staff in Tashkent, Uzbekistan found to have insufficient medical knowledge and the clinical decision-making abilities. The clinical performance of basic emergency management is good, but that of advanced emergency management seems to be marginal. The drug and medicines were enough, but medical equipment managing and monitoring the emergent patients was lack in ambulance of Tashkent. Training program for ambulance staff in Tashkent should be developed on the basis of the findings in this study. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: W.J., H.J.K. J.P., H.K.; Design: W.C.J., H.K., J.M.P., J.E.K., J.S.L.; Supervision: D.W.S., K.H.K., J.S.L.; Materials: W.J., H.J.K., J.P., H.K., J.E.K; Data: W.C.J., H.K., D.W.S., J.S.L.; Analysis: W.C.J., J.E.K., J.S.L., K.H.K., J.M.P.; Literature search: W.C.J., H.K., J.M.P.; Writing: W.C.J., H.K., J.S.L. Critical revision: K.H.K., D.W.S. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Macfarlane S, Racelis M, Muli-Muslime F. Public health in developing countries. Lancet 2000;356:841–6. 2. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2095–128. 3. Kobusingye OC, Hyder AA, Bishai D, Hicks ER, Mock C, Joshipura M. Emergency medical systems in low- and middle-income countries: recommendations for action. Bull World Health Organ 2005;83:626–31. 4. Suryanto, Plummer V, Boyle M. EMS systems in lower-middle income countries: a literature review. Prehosp Disaster Med. 2017;32:64–70. 5. Sidel VW. Feldshers and ‘’feldsherism’’ The role and training of the feldsher in the USSR. N Engl J Med 1968;278:987–92. 6. Ahmedov M, Azimov R, Mutalova Z, Huseynov S, Tsoyi E, Rechel B. Uzbekistan: health system review. Health Syst Transit 2014;16:1–137. 7. Kleinman ME, Brennan EE, Goldberger ZD, Swor RA, Terry M, Bobrow BJ, et al. Part 5: adult basic life support and cardiopulmonary resuscitation quality: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2015;132:S414–S35. 8. Jayaraman S, Sethi D, Chinnock P, Wong R. Advanced trauma life support training for hospital staff. Cochrane Database Syst Rev 2014;CD004173. 9. Link MS, Berkow LC, Kudenchuk PJ, Halperin HR, Hess EP, Moitra VK, et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S444–64. 10. Wyckoff MH, Aziz K, Escobedo MB, Kapadia VS, Kattwinkel J, Perlman JM, et al. Part 13: neonatal resuscitation: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2015;132:S543–S60. 11. Annane D, Siami S, Jaber S, Martin C, Elatrous S, Declère AD, et al.

Jeon et al. The importance of preliminary evaluation in developing ambulance staff training curriculum for developing countries Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA 2013;310:1809–17. 12. Olasveengen TM, Sunde K, Brunborg C, Thowsen J, Steen PA, Wik L. Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial. JAMA 2009;302:2222–9.

13. Wang HE. Paramedic endotracheal intubation. N C Med J 2007;68:272–5. 14 Gates S, Lall R, Quinn T, Deakin CD, Cooke MW, Horton J, et al. Prehospital randomised assessment of a mechanical compression device in out-of-hospital cardiac arrest (PARAMEDIC): a pragmatic, cluster randomised trial and economic evaluation. Health Technol Assess 2017;21:1–176.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Gelişmekte olan ülkeler için ambulans personeli eğitim ders programlarının geliştirilmesinde ön değerlendirmenin önemi: Özbekistan’da bir anket çalışması Dr. Woo Chan Jeon,1 Dr. Hyun Jong Kim,1 Dr. Junseok Park,1 Dr. Kyung Hwan Kim,1 Dr. Dong Wun Shin,1 Dr. Joon Min Park,1 Dr. Jung Eon Kim,1 Dr. Ji Sook Lee,2 Dr. Hoon Kim1 1 2

Inje Üniversitesi, Ilsan Paik Hastanesi, Acil Tıp Anabilim Dalı, Goyang-Kore Ajou Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Suwon-Kore

AMAÇ: Özbekistan Cumhuriyeti’nin başkenti olan Taşkent şehri, 2016 yılında ambulans hizmetlerinin kalitesini yükseltmek için Koreli acil servis doktorlarıyla ortak bir proje başlatmıştır. Taşkent’teki ambulans hizmeti, çok sayıda çağrıyı işleme koymakta zorluklarla yüz yüze gelmekte olup hastane öncesi ileri acil hasta bakımı sağlamada kadroları yeterince yetkin değildir. Ambulans personeli için uygun kapasite geliştirme eğitim programı tasarlamak için, Taşkent’teki mevcut ambulans hizmetini kaynaklar ve personel yeterliliği açısından incelendi. GEREÇ VE YÖNTEM: Ambulans personeli yapılandırılmış anket çalışmasına ve katılmış önceden geçerliliği onaylanmış yazılı teste katıldı. İstatistikler ve diğer bilgiler Özbekistan Sağlık Bakanlığı tarafından sağlandı. BULGULAR: Çalışmaya 98 ambulans personeli katıldı, yarıdan fazlası (%53.1) doktordu. Ambulansta ortalama hizmet süresi 8.71±6.9 yıldı. Ambulansta, resüsitasyon için büyük hacimli sıvılar haricinde kritik hasta tedavisi için enjektabl formları da içeren yeterli miktarda stoklanmış ilaç bulunmaktadır. Ambulansların sadece yüzde 19 ile 52’sinde gerekli monitörizasyon cihazları bulunuyordu. Temel prosedürlere ilişkin yeterlilik %60’tan daha yüksek düzeyde olmasına rağmen, ancak defibrilasyon gibi kritik hasta bakım becerileri %18 kadar düşük oranda bulundı. Yazılı teste yalnızca %41.1 oranında doğru yanıt verilmiş olmasına rağmen Kore ambulans personeli için validasyon testinde doğru yanıt oranı %60’dan yüksekti. Ambulans personeli için gerekli görülen geleneksel hastane öncesi bilgi ve beceri setinin testte marjinal düzeyde olduğu tespit edildi. TARTIŞMA: Özbekistan’ın Taşkent’teki ambulans personeli yetersiz tıbbi bilgi ve klinik karar verme yeteneklerine sahipti. Bu çalışmada elde edilen bulgular ışığında Taşkent’teki ambulans personeli için eğitim programı geliştirilmelidir. Anahtar sözcükler: Acil sağlık hizmetleri; kapasite geliştirme; öz değerlendirme programları; Özbekistan. Ulus Travma Acil Cerrahi Derg 2020;26(1):15-20

doi: 10.14744/tjtes.2019.79595

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ORIGIN A L A R T IC L E

Using pentraxin-3 for diagnosing acute appendicitis and predicting perforation: A prospective comparative methodological study Vahit Onur Gül, M.D.,1

Sabahattin Destek, M.D.2

Department of General Surgery, Gülhane Training and Research Hospital, Ankara-Turkey

Department of General Surgery, Bezmialem Vakıf University Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: In this study, we aimed to investigate the diagnostic performance of pentraxin-3 for acute appendicitis, and the predictive performance for perforation in patients with acute appendicitis, compared with white blood cell count, high-sensitivity Creactive protein and interleukin-6 (IL-6). METHODS: This study was a prospective methodological study, in which we studied the accuracies of the serum levels of pentraxin-3, white blood cell count, interleukin-6 and high-sensitivity C-reactive protein in estimating acute appendicitis, and in estimating perforation in patients with acute appendicitis. We designed the control group with the patients diagnosed inguinal hernia and admitted for elective surgery. Receiver operating characteristics analysis was used to compare the diagnostic accuracies and predictive performances. RESULTS: Receiver operating characteristics analysis revealed that the Pentraxin-3 level >3.67 ng/mL showed the sensitivity of 95.5% and specificity of 100.0% for diagnosing acute appendicitis, with an area under the curve of 0.993 (95% CI 0.967–1.000). Also, the Pentraxin-3 level >9.56 ng/mL showed the sensitivity of 92.9%, and the specificity of 87.1% for the prediction of the perforation, with an area under the curve of 0.820 (95% CI 0.736–0.886). CONCLUSION: The diagnostic performance of Pentraxin-3 for acute appendicitis and the predictive performance for perforation were higher than white blood cell count, high-sensitivity C-reactive protein and interleukin-6. Keywords: Acute appendicitis; high-sensitivity C-reactive protein; interleukin-6; pentraxin-3; white blood cell count.

INTRODUCTION Acute abdominal pain is one of the main complaints in patients presenting to the emergency department (ED).[1] Acute appendicitis (AA) is one of the most common clinical diagnoses requiring surgical intervention in patients with abdominal pain, with a reported prevalence of 8% in the general population.[2,3] Distinguishing AA from the other causes of abdominal pain before the specific surgical treatment is still a challenge.[1] On the other hand, the timely accurate diagnosis before the appendectomy is necessary because the prolonged diagnosis process puts the patient at risk of perforation, and

that may lead to prolonged hospitalization and broad-spectrum antimicrobial treatment.[4–6] White blood cell (WBC) count, inflammatory cytokines, such as C reactive protein (CRP) and Interleukins (ILs), and imaging techniques, such as ultrasonography (US) and computed tomography (CT) are widely used to make correct diagnosis and used to decide which patient should be taken to surgery.[5,7,8] WBC count is the most commonly measured markers in patients with the infectious or non-infectious presumed diagnosis. However, its rational use is generally to support the suspected clinical conditions, and it is neither sensitive nor

Cite this article as: Gül VO, Destek S. Using Pentraxin-3 for diagnosing acute appendicitis and predicting perforation: A prospective comparative methodological study. Ulus Travma Acil Cerrahi Derg 2020;26:21-29. Address for correspondence: Vahit Onur Gül, M.D. Gülhane Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara, Turkey Tel: +90 312 - 304 50 16 E-mail: vonurgul@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):21-29 DOI: 10.14744/tjtes.2019.27916 Submitted: 10.08.2019 Accepted: 04.12.2019 Online: 30.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Gül et al. Using Pentraxin-3 for diagnosing acute appendicitis and predicting perforation

specific for the diagnosis of AA.[2,7] CRP is also a widely used inflammatory marker and more specific than the WBC count. However, the diagnostic performance of the CRP for the determining severity of disease or complication is lower in the early phase of the infection because the elevation of CRP requires time approximately 48 hours or over. Interleukin-6 is a cytokine with an extensive range of biological activities. On the immune system, it has a wide range of impact, and it can affect the homeostatic process by having hormone-like characteristics. Interleukin-6 is widely used in clinical intervention because it has both anti and pro-inflammatory properties.[7] Imaging techniques have improved accuracy for the diagnosis of AA, but the qualified personal for the US are not available in all health care institutions. The inability to visualize the normal appendix is considered a major weakness of using the US in examining patients with suspected AA.[9] CT is an advanced technique that is not available at all EDs and associated with exposure to the radiation. Thus, these characteristics negatively affect the widely usage in clinical practice.[10] Pentraxin-3 (PTX 3) is the prototype of a long pentraxin group, and it is synthesized locally at the site of inflammation in response to inflammatory cytokine and microbial component.[1,11–13] Both CRP and PTX-3 exhibit low plasma levels in healthy humans and their levels rise in inflammatory situations.[14] However, the rate of increase and the time to reach the maximum level show differences, with CRP reaching its maximum peak at 48 hours and PTX-3 in 6–8 hours. [1,15,16] The delayed increase of the CRP in the inflammatory situations affects negatively the diagnostic and discriminative performance. More rapid increase seen in PTX-3 is likely due to its local production by many cells, as well as the release of the PTX-3 stored in specific granules in the neutrophils and monocytes.[1,17] This distinctive characteristic makes it a popular inflammatory marker for severe infectious diseases. An increase in PTX 3 in the circulation during the early phase of sepsis, septic shock and various infectious disorders and a correlation between its elevation and the severity of infection were shown in the literature.[11,18–21] There are few published studies that have investigated the diagnostic performance of PTX 3 for AA in patients with abdominal pain, and quite rare studies investigating the predictive performance for complication. Considering the above-mentioned characteristics of PTX 3, in this study, we aimed to investigate its diagnostic accuracy for AA and predictive performance for perforation by comparing WBC count, CRP and IL 6.

MATERIALS AND METHODS Study Design and Setting This study was a prospective methodological study, in which we studied the accuracies of the serum levels of PTX-3, WBC, IL-6 and hs-CRP in estimating AA in patients with abdominal pain, and in estimating perforation in patients with AA. All 22

patients were informed about this study and its procedures and written informed consents were collected from the participants before their inclusion in the study. Our research was conducted in accordance with Good Clinical Practice standards and according to the Standards for the Reporting of Diagnostic accuracy studies (STARD).[22] The study was approved by the Ethics Committee. This study was carried out between 01.04.2017 to 30.11.2017 at a State Hospital. The hospital is a secondary level hospital with a-200 bed capacity, and approximately nearly 600000 patients are admitted annually.

Participants Patients who admitted to our general surgery clinic with prediagnosis of AA between the study period were evaluated for eligibility as cases. Patients with symptoms, such as acute abdominal pain, nausea, vomiting, anorexia and right lower quadrant tenderness, were evaluated with a medical history, physical examination, blood test, abdominal ultrasonography (USG) and abdominal computerized tomography (CT) to pre-diagnose AA. Patients diagnosed with inguinal hernia and admitted to our clinic for elective surgery were defined as candidate controls. Patients under 18 years old, over 65 years old, pregnant, with immune system disorders and/or with active infection were excluded from both case and control arms of this study.

Test Methods All the serum markers were measured in the same serum sample concurrently. The serum levels of PTX3, WBC, IL-6 and hs-CRP were used data in estimating AA, and in estimating perforation in patients with AA. Venous blood samples taken from the patient group and control group into hemogram test tubes containing EDTA were centrifuged at 15 minutes at 1000 x g within 30 minutes of collection, and then, they were stored at -40°C until the day that the analysis was performed. Pentraxin 3 (Human Pentraxin 3/ TSG-14 Immunoassay Kit) and IL-6 (Human IL-6 Quantikine Elisa Kit) were measured by RT-2100 C Microplate Reader (Rayto Life and Analytical Sciences Co., Ltd., China). CRP levels were measured by the nephelometric method in the RADIM Delta nephelometer (Radim Diagnostics, Pomezia, Italy). WBC count was measured by an automated hematology analyzer (Sysmex Corporation, Kobe, Japan). There were two reference standards of this study: (1) diagnosed AA, (2) perforated AA. AA was defined as inflammation of the vermiform appendix, and perforated AA was defined as a hole in the appendix or a presence of fecalith in the abdomen. AA and perforated AA were diagnosed with surgical exploration and pathologic examination.

Data Analysis We did not calculate a priori required sample size. We collected the data of the patients admitted to our clinic between Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Gül et al. Using Pentraxin-3 for diagnosing acute appendicitis and predicting perforation

study period, who had inclusion criteria, who did not have exclusion criteria, and who accepted to involve in this study.

best cut-off values. P<0.05 was considered as statistically significance level.

Statistical analyses were performed using SPSS version 23 (IBM Corp. in Armonk, NY) and Medcalc version 16 (MedCalc Software bvba, Ostend, Belgium). Descriptive statistics were presented as frequency (n) and percentage (%) for categorical variables and median with interquartile range (IQR) for non-normally distributed variables. Pearson chi-square test or Fisher’s exact test was used for comparing categorical variables, and the Mann-Whitney U test was used for comparing non-normally distributed continuous variables among the study groups. The ROC analysis was used for comparing the accuracy of the serum levels of PTX-3, WBC, IL-6 hs-CRP in estimating AA, and in estimating perforation in patients with AA. The area under ROC curves (AUCs) for these markers was calculated, and DeLong et al.[23] method was used for comparing AUCs. Youden J index was used for estimating the best cut-off values. Sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), accuracy with 95% confidence intervals (CIs) were calculated for those estimated

RESULTS From 01.04.2017 to 30.11.2017, 143 patients admitted to our general surgery clinic with pre-diagnosis of AA, 25 were excluded from this study, and 118 patients were considered eligible cases for this study. Between the same period, 114 patients admitted to our clinic with an inguinal hernia for undergoing elective surgery, 49 of them were excluded, and finally, 65 patients were defined as candidate controls. All the eligible cases (n=118) and the controls (n=65) accepted to include in this study after giving information about this study and its procedures. The serum levels of the PTX-3, WBC, IL-6 and hs-CRP were measured at the admission in all of the eligible patients (n=183). Finally, we followed up all pre-diagnosed AA cases for the presence of acute appendicitis (AA) and/or for the occurrence of perforation. Of 118 cases that underwent surgery, six were negative appendicitis, and five of them were mesenteric lymphadenitis, and one case was Meckel’s diverticulitis (Fig. 1). Patients with the prediagnosis of AA (n=143)

Excluded (n=49) • <18 years old (n=12) • >65 years old (n=3) • Pregnant (n=2) • With immune system disorders (n=3) • With active infection (n=29)

Eligible cases (n=118) Candidate controls (n=114)

Eligible controls (n=65)

PTX-3, WBC, IL-6, hs-CRP tests were performed (n=65)

Controls (n=65)

Excluded (n=25) • <18 years old (n=14) • >65 years old (n=2) • Pregnant (n=5) • With immune system disorders (n=1) • With active infection (n=3)

PTX-3, WBC, IL-6, hs-CRP tests were performed (n=118)

Patients operated on the prediagnosis of AA (n=118)

Non-perforated AA (n=84)

Excluded because of negative AA (n=6) • With mesenteric lymphadenitis (n=5) • With Meckel’s diverticulitis (n=1)

Perforated AA (n=28)

Analyzed (n=177)

Figure 1. Flow diagram of this study. PTX-3: Pentraxin 3; WBC: White blood cell counts; IL-6: Interleukin 6; hsCRP: High sensitivity C-reactive protein.

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Gül et al. Using Pentraxin-3 for diagnosing acute appendicitis and predicting perforation

Table 1. Demographics and clinical characteristics of the participants Variables

Non–AA (n=65)

Age (years), Median (IQR)

AA p Non–perforated Perforated (n=112) (n=84) (n=28)

33.0 (25.5–40.0)

27.0 (22.3–35.0)

0.002

27.0 (22.3–35.0)

27.0 (22.3–40.5)

0.709

30 (46.2)

53 (47.3)

0.881

41 (48.8)

12 (42.9)

0.585

Female, n (%)

Time of pain onset, n (%)

Less than 8 hours

80 (95.2)

2 (7.1)

More than 8 hours

4 (4.8)

26 (92.9)

<0.001

PTX-3 (ng/mL), Median (IQR)

0.98 (0.56–1.57)

7.65 (5.44–10.61)

<0.001

7.09 (4.91–8.88)

13.89 (9.07–17.45)

<0.001

WBC (×109/L), Median (IQR)

7.8 (6.7–9.7)

12.3 (9.9–14.5)

<0.001

12.0 (9.8–13.0)

14.5 (12.3–17.3)

<0.001

532.2 (251.3–737.3)

<0.001

88.7 (41.9–122.9)

0.001

IL-6 (pg/mL), Median (IQR) hs-CRP (mg/L), Median (IQR)

30.0 (20.4–46.8) 294.6 (120.4–534.3) 2.5 (1.5–3.9)

51.2 (22.5–89.4)

<0.001 250.8 (87.6–436.8) <0.001

42.2 (21.1–81.1)

AA: Acute appendicitis; PTX-3: Pentraxin-3; WBC: White blood cell; IL-6: Interleukin 6; hs-CRP: High sensitivity C–reactive protein.

Of the 177 patients who were included in the analysis, 65 were the patients without AA, and 112 were the patients with AA. Of the patients with AA, 84 had non-perforated AA, and 28 had perforated AA. The median age was 33.0 year in the non-AA group, 27.0 year in the AA group. This difference was found statistically significant (p=0.002). The ages of the non-perforated and perforated groups were similar. The sex ratio of the groups was also found similarly. The time of pain onset was substantially less than eight hours in the non-perforated group; however, more than eight hours in the perforated group. Both of the serum levels of the PTX-3, WBC, IL-6 and hs-CRP were statistically significantly higher in AA group than non-AA group (p<0.001, p<0.001, p<0.001, p<0.001, respectively). Likewise, all the marker levels were statistically significantly higher in the perforated group than non-perforated group (p<0.001, p<0.001, p<0.001, p<0.001, respectively) (Table 1, Fig. 2).

(b) PTX-3 (ng/mL)

45 40 35 30 25 20 15 10

For the calculated best cut-off points, the sensitivity and specificity of PTX-3 were 95.5% and 100.0%; the sensitivity and specificity of WBC count were 67.9% and 96.9%; the sensitivity and specificity of IL-6 were 93.8% and 84.6%; and the sensitivity and specificity of hs-CRP were 94.6% and

(c)

(d)

45 40 35 30

25 20 15 10

(e)

4000

3000

2000

1000

1000 0

0 AA

Non-AA

Non-perforated

Perforated

Non-perforated

Perforated

(h)

1000 900 800 700 600 500 400 300 200 100 0

hs-CRP (mg/L)

5000

Non-AA

(g)

6000

5000

5 AA

Perforated

(f)

6000

Non-perforated

Non-AA

5 0

hs-CRP (mg/L)

(a)

The areas under ROC curves (AUCs) were 0.993 for PTX-3, 0.870 for WBC, 0.927 for IL-6 and 0.978 for hs-CRP in estimating acute appendicitis. The difference between AUCs for PTX-3 and WBC, and for PTX-3 and IL-6 were statistically significant (p<0.001 and p=0.001, respectively). Besides, the difference between AUCs for PTX-3 and hs-CRP was statistically significantly similar. The best cut-off points for PTX3, WBC, IL-6 and hs-CRP, estimated by Youden J indexes (0.955, 0.648, 0.784 and 0.870, respectively) were >3.67 ng/ mL, >11.0 x109/L, >55.2 pg/mL and >9.7 mg/L, respectively (Fig. 3 and Table 2).

Non-AA

Non-perforated

Perforated

Figure 2. Distributions of the serum levels of PTX-3 (a, b), WBC (c, d), IL-6 (e, f) and hs-CRP (g, h) among the study groups. PTX-3: Pentraxin 3; WBC: White blood cell counts; IL-6: Interleukin 6; hs-CRP: High sensitivity C-reactive protein.

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Gül et al. Using Pentraxin-3 for diagnosing acute appendicitis and predicting perforation Table 2. Comparison of the Area under ROC Curves for estimating acute appendicitis

AUC (95% CI)

Youden index (95% CI)

Associated cut-off

Pentraxin 3 (ng/mL)

0.993 (0.967–1.000)

0.955 (0.904–0.982)

>3.67

White blood cell counts (×109/L)

0.870 (0.811–0.916)

<0.001

0.648 (0.536–0.723)

>11.0

Interleukin 6 (pg/mL)

0.927 (0.878–0.960)

0.001

0.784 (0.660–0.861)

>55.2

hs-CRP (mg/L)

0.978 (0.944–0.994)

0.131

0.870 (0.766–0.916)

>9.7

AUC: Area under the curve; hs-CRP: CI: Confidence interval; High sensitivity C-reactive protein.

Table 3. Diagnostic results of PTX-3, WBC, IL-6 and hs-CRP by the occurrence of acute appendicitis Test PTX-3 >3.67 (ng/mL)

Sensitivity (95% CI)

Specificity (95% CI)

+LR (95% CI)

-LR (95% CI)

Accuracy

95.5 (89.9–98.5)

100.0 (94.5–100.0)

–

0.05 (0.02–0.10)

97.2

WBC >11.0 (×10 /L)

67.9 (58.4–76.4)

96.9 (89.3–99.6)

22.1 (5.6–86.8)

0.33 (0.30–0.40)

78.5

IL-6 >55.2 (pg/mL)

93.8 (87.5–97.5)

84.6 (73.5–92.4)

6.1 (3.4–10.8)

0.07 (0.04–0.20)

90.4

hs-CRP >9.7 (mg/L)

94.6 (88.7–98.0)

92.3 (83.0–97.5)

12.3 (5.3–28.6)

0.06 (0.03–0.10)

93.8

LR: Likelihood ratio; CI: Confidence interval; PTX-3: Pentraxin 3; WBC: White blood cell counts; IL-6: Interleukin 6; hs-CRP: High sensitivity C-reactive protein. Note: Accuracy is the sum of the number of true positive and the number of true negative patients.

92.3%, respectively, in estimating AA although the accuracies of PTX-3, WBC count, IL-6 and hs-CRP were 97.2%, 78.5%, 90.4% and 93.8%, respectively (Table 3).

For the calculated best cut-off points, the sensitivity and specificity of PTX-3 were 92.9% and 87.1%; the sensitivity

100

Sensitivity

The areas under ROC curves (AUCs) were 0.820 for PTX3, 0.744 for WBC, 0.729 for IL-6 and 0.711 for hs-CRP in estimating perforation in patients with AA. The differences between AUCs for PTX-3 and for the other markers were

statistically significantly similar. The best cut-off points for PTX-3, WBC, IL-6 and hs-CRP, estimated by Youden J indexes (0.560, 0.417, 0.405 and 0.381, respectively) were >9.56 ng/ mL, >13.0 x109/L, >492.0 pg/mL and >82.0 mg/L, respectively (Fig. 4 and Table 4).

PTX-3 WBC IL-6 hs-CRP

0 0

40 60 100 - Specificity

100

Figure 3. ROC Curves of PTX-3, WBC, IL-6 and hs-CRP for estimating acute appendicitis. PTX-3: Pentraxin 3; WBC: White blood cell counts; IL-6: Interleukin 6; hs-CRP: High sensitivity C-reactive protein.

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

40 60 100 - Specificity

100

Figure 4. ROC curves of PTX-3, WBC, IL-6 and hs-CRP for estimating perforation. Note: ROC curves of the IL-6 and CRP were overlapped. PTX-3: Pentraxin 3; WBC: White blood cell counts; IL-6: Interleukin 6; hs-CRP: High sensitivity C-reactive protein.

Gül et al. Using Pentraxin-3 for diagnosing acute appendicitis and predicting perforation

Table 4. Comparison of the Area under ROC Curves for estimating perforation in patients with acute appendicitis

AUC (95% CI)

Youden index (95% CI)

Associated cut-off

Pentraxin 3 (ng/mL)

0.820 (0.736–0.886)

0.560 (0.358–0.667)

>9.56

White blood cell counts (×109/L)

0.744 (0.653–0.822)

0.322

0.417 (0.220–0.548)

>13.0

Interleukin 6 (pg/mL)

0.729 (0.636–0.808)

0.212

0.405 (0.214–0.549)

>492.0

hs-CRP (mg/L)

0.711 (0.617–0.792)

0.143

0.381 (0.191–0.524)

>82.0

AUC: Area under the curve; hs-CRP: CI: Confidence interval; High sensitivity C-reactive protein.

Table 5. Diagnostic results of PTX-3, WBC, IL-6 and hs-CRP by the occurrence of perforation in patients with acute appendicitis Test

Sensitivity (95% CI)

Specificity (95% CI)

+LR (95% CI)

–LR (95% CI)

Accuracy

PTX-3 >9.56 (ng/mL)

92.9 (87.6–96.4)

87.1 (75.1–94.6)

7.2 (3.6–14.3)

0.08 (0.05–0.1)

81.3

WBC >13.0 (×109/L)

99.3 (96.4–100.0)

85.2 (72.9–93.4)

6.7 (3.5–12.7)

0.01 (0.00–0.05)

74.1

IL-6 >492.0 (pg/mL)

60.7 (40.6–78.5)

79.8 (69.6–87.7)

3.0 (1.8–5.0)

0.49 (0.30–0.80)

75.0

hs-CRP >82.0 (mg/L)

60.7 (40.6–78.5)

77.4 (67.0–85.8)

2.7 (1.6–4.4)

0.51 (0.30–0.80)

73.2

LR: Likelihood ratio; CI: Confidence interval; PTX–3: Pentraxin 3; WBC: White blood cell counts; IL–6: Interleukin 6; hs–CRP: High sensitivity C–reactive protein. Note: Accuracy is the sum of the number of true positive and the number of true negative patients.

and specificity of WBC count were 99.3% and 85.2%; the sensitivity and specificity of IL-6 were 60.7% and 79.8%; and the sensitivity and specificity of hs-CRP were 60.7% and 77.4%, respectively, in estimating perforation in patients with AA. Besides, the accuracies of PTX-3, WBC count, IL-6 and hs-CRP were 81.3%, 74.1%, 75.0% and 73.2%, respectively (Table 5). No adverse event had been seen neither in collecting the serum samples nor in evaluating or managing the patients with AA.

DISCUSSION We found that WBC count, CRP, IL6 and PTX 3 levels were significantly higher in the patients with AA than in the patients without AA. To evaluate the clinical significant diagnostic performance of these studied parameters, we applied a ROC curve analysis. The AUC of the PTX 3 value was the highest among all studied markers in our study. Nowadays, public health interventions at the individual and population levels aim to prevent disease, protect and promote health are more popular than the classical diagnosis and treatment approaches.[24,25] However, the burden on health care institutions increases day by day, and ED crowding is one of the major global healthcare issues.[26] For optimal use of healthcare resources in the EDs, early identification of definitive diagnosis, recognition of disease severity and prediction of complication is of major importance.[26] AA is one of the most common surgical emergencies encountered in the EDs.[5,27] The traditional approach in the diagnosis of AA 26

largely depends on clinical history, physical examination of patients and assessment of non-specific inflammatory markers.[1,10] WBC count and CRP are the most frequently used inflammatory cytokines, but the sensitivity and specificity for diagnostic accuracy were reported between 47%–74% and 55%–89% for WBC count and 39%–73% and 58%–97% for CRP, respectively in a meta-analysis.[10] The definitive treatment of AA is surgery and the traditional approach is not enough because that causes unnecessary surgery. It was reported that the negative appendectomy rate could reach up to 10 per cent in patients with performed appendectomy.[9,10] On the other hand, the delay in diagnosis of AA is related to the complications, such as perforation, and the mortality rate of uncomplicated AA is reported as 0.3%, it increases up to 6.0% in perforated cases.[6,28–32] Thus, new diagnostic and prognostic biochemical markers could benefit the assessment and management of patients with abdominal pain to have better guide the diagnosis of AA.[4,5] PTX 3 is an is an acute-phase protein that is rapidly synthesized and released in response to inflammatory cytokines, and its production directly reflects the affected tissue inflammatory response occurs.[18,33–35] It has been considered as a novel early diagnostic and prognostic biomarker in infectious illnesses, and our findings supported that PTX 3 is present very low level (<2 ng/mL) in normal humans.[17,33,36] The correlation between the level of the PTX 3 and disease severity was shown in the clinically important infectious conditions.[37–39] It was reported that the concentration of PTX 3 reached the maximum level in the early phase of patients with acute pancreatitis and then allowing distinction Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Gül et al. Using Pentraxin-3 for diagnosing acute appendicitis and predicting perforation

of the patients as mild, moderate and severe on the first day of disease.[40] Hamed et al.[33] showed that the plasma level of PTX 3 was able to discriminate patients with sepsis or septic shock significantly on the first day of infection. Hansen et al.[41] reported that a high PTX 3 level in patients with necrotizing soft tissue infection at the time of admission was associated with septic shock, amputation and risk of death. They emphasized that PTX 3 might be used to distinguish high-risk patients who require aggressive surgical treatment. Using ROC curve analysis, we demonstrated that PTX 3 has the highest positive likelihood ratio for the occurrence of the perforation, and this finding supports the importance of PTX 3 to foresee the severity of the disease.

Conclusion

While the conservative treatment approach of AA with antibiotics in the pediatric population has been accepted, this concept is controversial in the adult population, and the emergent appendectomy has been widely performed in adult patients presenting to the EDs.[27] In a recent metaanalysis demonstrated that delaying appendectomy for up to 24 hours might be an acceptable alternative for patients that have not risk factors of complicated appendicitis.[42] In addition, some studies reported that higher morbidity and error rates when working or operating at out of hours[42–44] because of an adequate number of staff could not be assigned in all EDs or emergency operating rooms at out of hours and required preoperative evaluations might not be performed.[42] If the patients that have a low risk for the complication could be defined, the emergent appendectomy could be postponed and the workload out of hours can be reduced.[27,45] Several markers or parameters have been studied for prediction of the complication. For example, Shin et al.[30] demonstrated that the delta neutrophil index is a good predictor for the perforation in adult patients with AA (sensitivity 67%, specificity 90%, AUC 0.807). Obinwa et al.[5] composed a clinical model, including a combination of anorexia, rebound tenderness, leukocytosis and pyrexia, to predict advanced appendicitis. They reported that this model might be useful in the early identification of patients with advanced AA, with a 38% sensitivity. Alvarez-Alvarez et al.[3] demonstrated serum fibrinogen as a good predictor for appendicular perforation, with a sensitivity of 86.77%, a specificity of 91.49, a positive predictive value of 93.65 and, a negative predictive value of 82.69. In the presented study, the predictive accuracy of PTX-3 in estimating perforation in patients with AA was 81.3 (the sensitivity and specificity of PTX-3 were 92.9 and 87.1) with a +LR of 7.2 and a –LR of 0.08.

Peer-review: Internally peer-reviewed.

There are several limitations to the present study. Firstly, our study has a relatively small sample size given that this study was conducted in a single center. More than one PTX 3 value could have been measured, and then, the increase and decrease or the timely rate of increase or decrease according to first value might guide the diagnosis or the risk of perforation. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

In the present study, we demonstrated that PTX 3 values were significantly higher in patients with AA compared to the patients without AA and significantly higher in patients with perforation than in patients without perforation. In addition, both the diagnostic performance for AA and the predictive performance for perforation were higher than WBC, hs-CRP and IL. The usefulness of PTX 3 as a diagnostic and predictive marker for AA should be validated in prospective randomized controlled studies. Ethics Committee Approval: Approved by the local ethics committee. Authorship Contributions: Concept: V.O.G; Design: V.O.G; Supervision: V.O.G; Fundings: V.O.G; Materials: V.O.G; Data: V.O.G; Analysis: V.O.G; Literature search: V.O.G; Writing: V.O.G; Critical revision: V.O.G., S.D. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

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Gül et al. Using Pentraxin-3 for diagnosing acute appendicitis and predicting perforation

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut apandisit tanısını koymak ve perforasyonu öngörmek için pentraxin-3 kullanımı: İleriye yönelik karşılaştırmalı metodolojik çalışma Dr. Vahit Onur Gül,1 Dr. Sabahattin Destek2 1 2

Gülhane Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara Bezmialem Vakıf Universitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul

AMAÇ: Biz bu çalışmada, pentraxin-3’ün akut apandisit için tanısal performansını ve perforasyon için prediktif performansını, beyaz küre sayısı, yüksek duyarlıklı C-reaktif protein ve interlökin-6 ile karşılaştırmayı amaçladık. GEREÇ VE YÖNTEM: İleriye yönelik metodolojik türde olan bu çalışmada, pentraxin-3, beyaz küre sayısı, yüksek duyarlıklı C-reaktif protein ve interlökin-6’nın akut apandisit için tanısal performansı ve akut apandisitli hastalarda perforasyon için prediktif performansı karşılaştırıldı. Kontrol grubunu, inguinal herni tanısı alan ve kliniğimize elektif cerrahi için başvuran hastalardan oluşturuldu. Tanısal doğruluk ve prediktif gücünün karşılaştırmasında “receiver operating characteristics’ analizi kullanıldı. BULGULAR: Serum pentraxin-3 düzeyi >3.67 ng/mL olması, akut apandisit tanısı için %95.5 sensitivite ve %100.0 spesifisiteye sahipken eğri altındaki alan %0.993 (%95 CI 0.967–1.000) olarak bulundu. Ayrıca pentraxin-3 düzeyi >9.56 ng/mL olması, perfore akut apandisit prediksiyonu için %92.9 sensitivite ve %87.1 spesifisiteye sahipken, eğri altındaki alan 0.820 (%95 CI 0.736–0.886) olarak bulundu. TARTIŞMA: Pentraxin-3’ün akut apandisit için tanısal performansı ve perforasyon için prediktif gücü beyaz küre sayısı, yüksek duyarlıklı C-reaktif protein ve interlökin-6’ya göre yüksek bulunmuştur. Anahtar sözcükler: Akut apandisit; beyaz küre sayımı; interlökin-6; pentraxin-3; yüksek duyarlıklı C-reaktif protein. Ulus Travma Acil Cerrahi Derg 2020;26(1):21-29

doi: 10.14744/tjtes.2019.27916

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ORIGIN A L A R T IC L E

Comparison of epidural analgesia combined with general anesthesia and general anesthesia for postoperative cognitive dysfunction in elderly patients Günseli Orhun, M.D.,1 Zerrin Sungur, M.D.,1 Kemalettin Koltka, M.D.,1 Meltem Savran Karadeniz, M.D.,1 Hacer Ayşen Yavru, M.D.,1 Hakan Gürvit, M.D.,2 Mert Şentürk, M.D.1 1

Department of Anesthesiology and Intensive Care, İstanbul University İstanbul Faculty of Medicine, İstanbul-Turkey

Department of Neurology, Behavioral Neurology and Movement Disorders Unit, İstanbul University İstanbul Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: Cognitive dysfunction in the early postoperative course is common for the elderly population. Anesthetic management may affect postoperative cognitive decline. Effective analgesia, early recovery and modulation of the stress response are advantages of neuraxial blocks. This study aims to compare the effects of general anesthesia and the combination of general anesthesia with epidural analgesia for postoperative cognitive dysfunction (POCD). We hypothesized that neuraxial block combined with general anesthesia (GA) would have a favorable influence on POCD prevention. METHODS: Patients above 60 years undergoing non-cardiac surgery were included in this randomized, prospective study and randomized into two groups. Patients in the first group (GI) were treated under GA, whereas in the second group (GII), epidural analgesia was combined with GA. Patients’ cognitive function was assessed before and one week after surgery using a neuropsychological test battery. POCD was defined as a drop of one standard deviation from baseline on two or more tests. RESULTS: A total of 116 patients were allocated for the final analysis. Demographic and operative data were similar between groups, except maximum pain scores, which were significantly higher in GI than GII (4.9±2.8 vs. 1.7±1.7; p<0.001, respectively). The incidence of POCD was comparable between groups (26% in GI and 24% in GII). Memory performance, visuospatial functions, and language skills tests were significantly higher in GII compared to GI. CONCLUSION: General anesthesia and epidural analgesia combined with general anesthesia resulted in similar POCD in elderly patients undergoing abdominal surgery. However, in combined anesthesia group memory, language skills and visuospatial functions appeared to be better preserved. Effective pain control might contribute to preventing cognitive decline in some domains. Keywords: Cognitive dysfunction; elderly; epidural analgesia; general anesthesia; postoperative pain.

INTRODUCTION Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients under general anesthesia, and also regional anesthesia.[1–3] POCD is commonly defined as some deficits in cognition and memory with a wide range of severity.[1,2] Patients may complain from mild impairment of concentration, difficulties in learning, decreased verbal abil-

ities, and trouble in reasoning. The diagnosis is quite complicated and requires neuropsychological tests, although a unanimously accepted methodology is still lacking.[4] Cognitive decline may recover in early or late during the postoperative course or persist as a precursor of dementia, which will appear from months to years in susceptible subjects, without any recovery in the initial POCD phase.[5] Defined risk factors for patients are known as advanced age and lower educational

Cite this article as: Orhun G, Sungur Z, Koltka K, Savran Karadeniz M, Yavru HA, Gürvit H, et al. Comparison of epidural analgesia combined with general anesthesia and general anesthesia for postoperative cognitive dysfunction in elderly patients. Ulus Travma Acil Cerrahi Derg 2020;26:30-36. Address for correspondence: Zerrin Sungur, M.D. İstanbul Üniversitesi İstanbul Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, İstanbul, Turkey Tel: +90 212 - 631 87 67 E-mail: zerrin_sr@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(1):30-36 DOI: 10.14744/tjtes.2019.04135 Submitted: 15.10.2019 Accepted: 06.11.2019 Online: 30.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Orhun et al. Comparison of epidural analgesia combined with GA and GA for POCD in elderly patients

level hence decreased cognitive reserve. Meanwhile, cardiac, major vascular, and hip fracture surgeries are generally associated with POCD.[5] The incidence of POCD for non-cardiac surgery varies from 5 to 40% in studies.[6] Moreover, it may reach 40 to 60% for cardiac and hip fracture procedures.[2,6] The general etiology is currently unclear but seems probably multifactorial as established after the publication of the International Study of Postoperative Cognitive Dysfunction (ISPOCD) study twenty years ago.[1] Recent reports have pointed out an imbalance of the neurotransmitter system. [7] In the presence of decreased neurobiologic reserve (as may be seen in the elderly population), inflammatory mediators may contribute to the neurocognitive decline. Elevated postoperative cytokines are found to be associated with both early and mid-stage cognitive impairment for cardiac and noncardiac surgery.[8] The effects of anesthetics have already been investigated in previous studies; general anesthesia was often compared to regional methods for appropriate surgery,[3,9] with the negligible incidence of POCD between two techniques. Volatile anesthetics were blamed for amplifying effects of cerebral insults, enhancing neuronal apoptosis, or even causing irreversible cerebral damage in experimental studies. However, results from human studies with inhalational anesthetics are controversial, some with favorable,[10] some with poorer outcomes.[11] Neuraxial blocks offer some advantages, such as adequate pain control, modulation of stress response triggered by surgery, early mobilization. Neuraxial block ismostly investigated in hip replacement surgery and found to be associated with a similar prevalence of POCD compared to general anesthesia.[12,13] Epidural analgesia seems, however, suitable for the elderly population as it allows a reduction in both preoperative anesthetics and perioperative opioid use (which may affect cognitive decline via hyperalgesic effects, sleep disturbance), thereby allowing early discharge. This study aims to compare the effects of general anesthesia and epidural analgesia-general anesthesia combination for elderly patients undergoing non-cardiac surgery on cognitive function. We hypothesized that neuraxial block combined to general anesthesia would have a favorable influence on POCD prevention compared to general anesthesia alone.

MATERIALS AND METHODS After approval of the Institutional Review Board (2007/2607), patients undergoing non-cardiac elective surgery were enrolled in this prospective, double-blind, randomized study. Investigators who treated patients in the perioperative period (KK, MSK, AY) were unaware of cognitive results, and viceversa two researchers (GO, HG) who were in the neurological evaluation did not participate in the perioperative course. The written informed consent was obtained from each participant after a full explanation of the procedure. Other inclusion criteria were as follows: patients above 60 years old; surgical procedures lasting more than one hour; and at least Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

four days of hospital stay. The exclusion criteria were determined as history of major psychiatric disease and dementia or any disease of the central nervous system (meningitis and encephalitis, brain tumors, neurodegenerative, inflammatory, cerebrovascular disease) according to medical records; patients with a preoperative Mini-Mental State Examination (MMSE)[14] score below 23; prior neurosurgical, vascular or cardiac surgeries; drug or alcohol dependence; speech disturbances; vision and hearing impairment; inadequate use of native language; patient’s refusal to participate to the study; and any contraindications for epidural analgesia. Any patient, who would require postoperative ICU stay, was also excluded from this study. Patients’ demographic data (age, gender, co-morbidities, education level) were recorded at the time of enrollment in the study. American Society of Anesthesiologists (ASA) physical status was also recorded. The ASA scale is the most commonly used system for the assessment of the physical status of patients undergoing surgery, as it is easy to perform and a good predictor of perioperative morbidity or mortality. No premedication was administered before surgery. In the operating room, eligible patients were randomly assigned into two groups via the sealed envelope technique. For the first group (GI), patients were treated solely under general anesthesia (GA), whereas in the second group (GII), epidural analgesia (EA) was combined with GA. Routine monitoring included ECG, noninvasive arterial pressure, and pulse oximeter (Horizon2000, Mennen Medical, Rehovot, Israel) for both groups. For GII, an epidural catheter (B. Braun, Melsungen, Germany) was inserted through the L2-3 or L3-4 intervertebral space, and placement of the catheter was verified by 3 ml of 2% lidocaine 1/200.000 adrenaline. In both groups, anesthesia induction was achieved with propofol (2–3 mg/kg), sufentanil (0.15–0.2 μg/kg) and rocuronium (0.6–0.9 mg/kg). Desflurane was administered in a mixture of 50% O2 with 50% NO2 for maintenance with sufentanil and rocuronium bolus doses according to patients’ requirements. Depth of anesthesia was monitored throughout surgery with bispectral index (BIS) (A-2000 BISTM monitor; System rev.2.1, AspectTM Medical Systems, Inc., Norwood, MA, USA). The desflurane concentration was adjusted to maintain a BIS value between 40 and 50. Postoperative analgesia was achieved with an opioid via intravenous patient-controlled analgesia pump in GI (Abbott Pain Management Provider; Abbott Laboratories, Istanbul, Turkey). The same pumps provided postoperative analgesia in GII via the epidural route with a mixture of opioids and local anesthetic. Operative data (type and duration of surgery, duration of anesthesia, transfusion requirement) were noted. Adverse events were defined as hypotension, hypoxia, serious bleeding, vasopressor therapy, and unplanned intensive care unit 31

Orhun et al. Comparison of epidural analgesia combined with GA and GA for POCD in elderly patients

stay. Emergent need for reoperation during the study period, removal of epidural catheter was determined as perioperative exclusion criteria. Pain evaluation with visual analogue scale (VAS), length of hospital stay, and multisystemic complications (such as pneumonia, dysrhythmia, myocardial ischemia, urinary infection, delirium) were followed during the postoperative period.

Neuropsychological Assessment Initially, patients were evaluated with a preliminary MMSE to exclude subjects fewer than 22 points. If patients scored equal or more than 23 on the MMSE, they were considered eligible for this study and were assessed with a brief neuropsychological test battery, designed with the purpose of covering all cognitive domains, on the one hand, and easily applicable by a clinician, on the other hand, not necessarily demanding an expert neuropsychologist. Thus, the battery was composed of many bedside mental status tests and a number of practical formal neuropsychological tests: The Wechsler Memory Scale-Revised (WMS-R) - Logical Memory Subtest (as a measure of episodic memory, with two different stories (A and B) pre-and postoperatively), the Clock Drawing Test (as a measure of executive functioning),[15] the Word List Generation Test (as a measure of sustained attention and language), the WMS-R-Digit Span Subtest (as a measure of global attention and working memory), and the Interlocking Finger Test (as a measure of visuospatial functions).[16] The episodic memory measure, which is called the Logical Memory subtest in WMS-R, is comprised of two different short stories, thus preventing the learning effect when repeated post-operatively. They are identically scored according to the number of items recalled by the subject out of the total number possible. Short-term free recall is the number of recalled items from the story immediately after the examiner, long-term free recall the number of recalled items from the story after a twenty minutes delay-period, during which other tests were performed. Among the various scores, the delayed free recall score is used as the measure. WMS-R was standardized in Turkish, and normative scores for its various subtests are available.[17] The executive function measure, the Clock Drawing Test, is a practical bedside mental test, which is qualitatively evaluated in clinical practice according to the placement of digits within a circle and then the placement of arms showing the demanded time. However, quantified versions of it have been developed for research purposes. We used the 10-point version developed by Manos and Wu standardized in Turkish by Emek Savaş et al.[18] in this study. Category fluency is used as the Word List Generation Test. Our version was the naming of as many animals as possible within one minute. This version was standardized in Turkish by Tumac as a master’s thesis.[19] WMS-R Digit Span Subtest is comprised of reciting of the heard random digits by the subject first in the same order (forward span-FS) and then in the reverse order (backward span-BS), and the last number of successfully recited digits makes the span. We used FS+BS as 32

a measure. The Interlocking Finger Test is a practical bedside test for visuospatial functions. The subject is instructed to imitate the hand postures of the examiner. These postures are not certain gestures, do not convey any symbolic message, and thus they are seen for the first time by the subject. We used five such postures and scored each as 2, for a correct imitation, as 1, for not exactly correct, yet attempted and resembling imitation and as 0, for unattempted or having no resemblance. This test has not been standardized in Turkish. Neuropsychological tests were first performed 2–3 days before surgery (baseline) and seven days after the operation. All evaluation was conducted by the same research investigator who was blinded to intraoperative anesthetic management (G.O.) and who was trained and supervised by the study consultant (H.G.) from the Department of Neurology during the entire study period. The neuropsychological test battery lasted approximately 45 minutes. All tests were administered at the same time of the day and the same location, a private room at surgical service. Postoperative cognitive dysfunction is defined according to decline for more than one standard deviation from baseline on two or more neuropsychological tests, as described by Höcker et al.[20] in their study. The standard deviation (SD) of each preoperative test was calculated, and the number of patients who deteriorated or improved postoperatively was determined.

Statistical Analysis The results of this study, SPSS 19.0 for WINDOWS software were used for statistical analysis. In assessing the study data, numerical values were shown as mean ± SD and compared via the student’s t-test (cognitive test results for inter and intragroup analysis). Categorical data were expressed as number and percentage; compared with Fischer’s exact test.

Sample Size Our preliminary results showed that 41% of geriatric patients operated under general anesthesia fulfill this definition of POCD.[20] To detect a difference of at least 20% in this proportion at a significance level of 5% (a=0.05) and a probability of 90% (b=0.10), power calculations revealed a sample size of n=55 per group.

RESULTS We included 129 patients meeting inclusion criteria, and 116 of them completed this study with 57 in GI and 59 in GII (Fig. 1). Demographic and perioperative data were similar between groups; except pain scores, which were significantly lower in GII (p<0.001) (Table 1). Perioperative hypotension was treated initially with the crystalloid bolus, and non-responder to volume therapy was treated with the vasopressor infusion. None of the hypotensive episodes lasted more than five minutes. Adequacy of pain therapy was evaluated with Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Orhun et al. Comparison of epidural analgesia combined with GA and GA for POCD in elderly patients

Table 2. Comparison of complications between groups (p>0.05)

Assessed for eligibility (n=132) Excluded due to - Lower MMSE (n=3) Enrolment (n=129) Randomization

Allocated to general anesthesia

(n= 64)

with epidural analgesia

Excluded due to second surgery

(n= 65)

(n=3)

Excluded due to unplanned ICU

Unplanned ICU (n=2)

(n=1)

Incomplete data (n=2)

Incomplete data (n=3) Inadvertent epidural catheter removal (n=2)

Completed study

(n=57)

(n=59)

Figure 1. Flow diagram summarising patient enrolment and randomization. MMSE: Mini-Mental State Examination; ICU: Intensive care unit.

the worst score as maximum VAS. Postoperative complications are summarized in Table 2. Cardiac complications were myocardial ischemia or supraventricular tachycardia. Complications did not show any difference Table 1. Patients demographic and perioperative data

Age (years) Gender (F/M) ASA score I–II/III

GI (n=57)

GII (n=59)

70.9±7.4

68.4±5.9

18/39

13/46

32/25

25/24

Ischemic heart disease

12 (21%)

10 (17%)

Diabetes mellitus

10 (18%)

8 (14%)

39/18

35/24

Education (<8 years/>8years) COPD

10 (18%)

7 (12%)

139.5±71.7

176.8±81.5

Peroperative hypotension

13 (23%)

17 (29%)

Transfusion requirement

18 (32%)

23 (39%)

4.9±2.8

1.7±1.7*

Operation time (min)

Visual analogue scale (max) Surgery

Urological

33 (58%)

37 (63%)

General surgery

24 (42%)

22 (37%)

12±8.9

10.6±7.7

Length of stay (day)

GI (n=57)

GII (n=59)

n % n %

Cardiac

4 7 2 2

Infection

Allocated to general anesthesia

Quantitative data are presented as mean±standard deviation. Qualitative data are presented as frequencies and percentages. ASA: American Society of Anesthesiologists; G1: General anesthesia; GII: General anesthesia with epidural analgesia; M: Male; F: Female; COPD: Chronic obstructive pulmonary disease. * P<0.01 compared to GI.

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Urinary

6 11 7 12

Pneumonia

4 7 3 5

Miscellaneous 3 5 4 4

between study groups (p>0.05). The incidence of POCD was not different among patients with or without complications (respectively 12 in 33 and 17 in 66; p=0.096). Neurocognitive test results are summarized in Table 3. Test results were compared between groups in both preoperative and postoperative periods. The comparison of individual test scores showed that patients in GII had significantly higher scores on memory, language, and visuospatial function tests (Table 3). In intragroup comparison, we did not find any significance between preoperative and postoperative values; except for MMSE in GI (p<0.05) (Table 3). The incidence of POCD was similar between groups 15 (26%) in GI and 14 (24%) in GII (p=0.83).

DISCUSSION In this prospective study, the incidence of POCD was similar between general anesthesia or general anesthesia combined with epidural analgesia groups in non-cardiac surgery. Compared to general anesthesia, its combination with epidural analgesia showed a trend of improvement in limited areas, such as short and long term memory, visuospatial functions, and language skills. To our knowledge, this is one of the rare studies comparing the effects of the combination of general anesthesia with epidural analgesia and general anesthesia alone for POCD after non-cardiac surgery in elderly patients. The incidence of POCD is well defined and mostly studied in cardiac surgery. As non-cardiac procedures are quite heterogeneous, relevant literature reports a large variety of incidence concerning POCD.[6] Early POCD at first week appeared between 17.1–41.4% for general, orthopedic, thoracic, or urological surgery. We observed 25% (29/116) of POCD in the overall study population, which is concordant with previous studies.[6] Although not completely clarified yet, postoperative cognitive dysfunction is a multifactorial phenomenon as a result of a combination of patient-related and surgery-related risk factors. Universally cited factors are older age, already impaired cognitive status, or generally lower education level, chronic 33

Orhun et al. Comparison of epidural analgesia combined with GA and GA for POCD in elderly patients

Table 3. Pre and postoperative neuropsychological test results comparing groups Neuropsychiatric test

Preoperative GI

Preoperative GII

Postoperative GI

Postoperative GII

Mini Mental test

27.02±2.04

27.88±1.84

25.7±3.84δ 27.11±2.55

WMS-R Logical Memory (short-term free recall)

6.79±3.05

7.71±2.88

6.45±3.80

8.20±3.15*

WMS-R Logical Memory (long-term free recall)

5.85±3.22

7.08±3.33

5.74±4.05

8.34±4.33**

Clock drawing test

6.70±3.52

7.74±3.24

6.68±3.55

6.80±3.46

WMS-R Digit span subtest (FS+BS)

8.55±2.47

8.20±2.39

7.95±2.54

7.82±2.03

Word list generation (#animals/min)

15.42±4.79

17.4±3.94

14.8±4.21

17.8±4.78**

Visuospatial function

8.08±2.05

8.40±1.68

7.27±2.90

8.48±1.77*

Quantitative data are presented as mean±standard deviation. MMSE: Mini-Mental State Examination; GI: General anesthesia; GII: General anesthesia with epidural analgesia. WMS-R: Wechsler Memory Scale-Revised; FS: Forward span; BS: Backward span. *GII significantly different compared to GI (p<0.05); **GII significantly different compared to GI (p<0.01). δGI postoperative significantly different compared to GI preoperative (p<0.05).

alcoholism.[5] Age appears to be the critical factor with volume and thickness loss in the prefrontal cortex, reduced antioxidant capacity, decreased levels of neurotransmitters, and associated receptors.[21] Cardiac or orthopedic procedures are mostly associated with POCD.[2,22] In the perioperative period, anesthetics are also blamed for triggering POCD;[23] meanwhile, there is no robust data to demonstrate the superiority of regional or local technics in this issue. The well-known ISPOCD study affirmed that regional anesthesia (RA) (spinal or epidural) was associated with reduced incidence of POCD compared to GA in major non-cardiac surgery early in the course; significant difference disappeared at the third month between study groups.[3] Controversies exist in the literature announcing no difference between GA and RA concerning cognitive performance. Two meta-analyses investigated the effects of GA and RA on POCD.[23,24] The previous one reported the potential association between GA and POCD, and authors encouraged the use of RA in patients prone to cognitive impairment.[23] The following meta-analysis, four years later, including 16 RCTs, concluded that no definitive data were showing the superiority of RA to prevent POCD in a large variety of surgeries.[24] In fact, they have common studies; however, the results of the former are almost non-significant, with an odds ratio of 1.34. Major concerns are the heterogeneity of studies (such as diagnosis of POCD, types of RA) and different sedation protocols added to various types of RA, which means that that none of the groups was devoid of anesthetics.[24] GA is indispensable in abdominal surgery, and combination with EA offers better pain control, reduced opioid use, and essentially modulation of the surgical stress response. Perioperative stress indispensable for recovery after surgery may substantially impair central nervous system homeostasis. Experimental and clinical studies revealed affected synaptic plasticity, dysregulation of the cholinergic system, altered microglial activation, or hippocampus dysfunction due to chaotic stress response.[25] The hippocampus, which was defined as crucial for memory function, appeared to be particularly vulnerable to neuroinflammation.[26] According to our 34

literature search, two randomized studies were comparing EA and GA combination with GA, one historic trial in the early 1980s, and the second in abdominal surgery.[12,27] The recent study affirmed comparable cognitive decline with GA and combined technique.[27] The authors commented that other factors (lower education level and general surgery) would affect mainly postoperative decline. In this study, we aimed to focus on a relatively homogenous surgery group from the point of the stress response. All subjects underwent an abdominal procedure, with minimal risk of embolism lasting more than two hours, and an average length of stay. In our study, not the incidence of POCD, but domains of cognitive decline were significantly different between groups. Memory function, verbal skills, and visuospatial function appeared to be better preserved in the combined group. The recent orthopedic trial reported similar results comparing GA with GA and peripheral block combination.[28] The authors explained the difference by the reduced opioid requirement in the combined group. During the early postoperative course, epidural analgesia provided reduced incidence of POCD compared to systemic opioids after hip fracture among octogenarians.[29] Pain control was successfully achieved in both groups. Regional techniques do not only offer adequate pain control (and decreased opioid need), but they also modulate cytokine response to surgery. Experimental studies ensued interesting results on postoperative pain and cognitive functions. The laparotomy model resulted specifically in spatial dysfunction, learning disability, or memory among rats presented as limited movement area or preference of corners. [30] However, improved analgesia prevented the development of memory deficits after laparotomy.[31] Increased pro-inflammatory cytokines accompany mostly the picture. The hippocampus known for vulnerability to inflammation coordinates learning and memory.[25,32] The effects of inflammation on the hippocampus have already been investigated in agerelated cognitive decline.[32] We observed remarkably better pain scores in combined anesthesia with acceptable scores in the GA group, which might contribute to preserved memory Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Orhun et al. Comparison of epidural analgesia combined with GA and GA for POCD in elderly patients

or visuospatial functions. As this study did not involve the measurement of the inflammatory response, we were concentrated on cognitive functions.

Conflict of Interest: None declared.

Postoperative complications were similar between study groups. Systemic complications were supposed to be associated with postoperative cognitive decline.[32] Respiratory complications and infections seemed to be related to POCD in a large study group.[33] However, investigators could not show statistical significance in multivariate analysis. The incidence of POCD was similar in patients with or without postoperative complications in this study. Larger trials should be designed to detect the effects of systemic complications.

REFERENCES

This study has some limitations. The major limitation is the absence of long-term results as a variable rate of early cognitive decline may recover. However, the detection of the incidence of late POCD was not the aim of this study, but it was focused on the early POCD for comparing two different anesthesia methods. The second limitation may be the definition of POCD, which differs among studies. Initially, the calculation of a composite z score is proposed based on a control group not exposed to surgery.[1] Subsequently, a decrease of more than 1 SD, at least on two neuropsychological tests, is proposed as a diagnostic criterion.[22] In our previous studies, we also used the second definition in cardiac surgery patients.[34,35] The third point may be that our test battery cannot be considered as a conventional “comprehensive” test battery since it was specially designed to be practical for use by an anesthesiologist (G.O), who was supervised by a behavioral neurologist (H.G). However, we think that this was not a major flaw, as incidence rates of POCD were similar to previous studies.

Financial Disclosure: The autors declared that this study has received no financial support.

1. Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of PostOperative Cognitive Dysfunction. Lancet 1998;351:857−61. 2. Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, et al; Neurological Outcome Research Group and the Cardiothoracic Anesthesiology Research Endeavors Investigators. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med 2001;344:395−402. 3. Rasmussen LS, Johnson T, Kuipers HM, Kristensen D, Siersma VD, Vila P, et al; ISPOCD2(International Study of Postoperative Cognitive Dysfunction) Investigators. Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients. Acta Anaesthesiol Scand 2003;47:260−6. 4. Funder KS, Steinmetz J, Rasmussen LS. Methodological issues of postoperative cognitive dysfunction research. Semin Cardiothorac Vasc Anesth 2010;14:119−22. 5. Evered LA, Silbert BS. Postoperative Cognitive Dysfunction and Noncardiac Surgery. Anesth Analg 2018;127:496−505. 6. Green CM, Schaffer SD. Postoperative cognitive dysfunction in noncardiac surgery: A review. Trends in Anaesthesia and Critical Care 2019;24:40−8. 7. Cascella M, Muzio MR, Bimonte S, Cuomo A, Jakobsson JG. Postoperative delirium and postoperative cognitive dysfunction: updates in pathophysiology, potential translational approaches to clinical practice and further research perspectives. Minerva Anestesiol 2018;84:246−60. 8. Liu X, Yu Y, Zhu S. Inflammatory markers in postoperative delirium (POD) and cognitive dysfunction (POCD): A meta-analysis of observational studies. PLoS One 2018;13:e0195659.

In conclusion, GA and EA, combined with GA, resulted in similar POCD in elderly patients undergoing abdominal surgery. However, in combined anesthesia group memory, linguistic and visuospatial functions appeared to be better preserved. Effective pain control in this group might have benefits in preventing cognitive decline in some domains. We think that more extensive studies, utilizing a comprehensive neuropsychological battery and also having a longer-term follow-up time points may better document the advantages of effective pain control on the cognitive functions of the elderly people undergoing surgery, who are already at risk for agerelated cognitive decline, such as Alzheimer’s disease.

9. Williams-Russo P, Sharrock NE, Mattis S, Szatrowski TP, Charlson ME. Cognitive effects after epidural vs general anesthesia in older adults. A randomized trial. JAMA 1995;274:44−50.

Ethics Committee Approval: The study was approved by the Institutional Review Board (approval number: 2007/2607), and signed consent was obtained from patients.

13. Tzimas P, Samara E, Petrou A, Korompilias A, Chalkias A, Papadopoulos G. The influence of anesthetic techniques on postoperative cognitive function in elderly patients undergoing hip fracture surgery: General vs spinal anesthesia. Injury 2018;49:2221−6.

Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: G.O., Z.S., H.G., M.Ş.; Design: G.O., Z.S., H.G., M.Ş.; Supervision: Z.S., H.G., M.Ş.; Materials: G.O., K.K., M.S.K., A.Y.; Data: G.O., K.K., M.S.K., A.Y.; Analysis: Z.S., H.G., M.Ş.; Literature search: G.O., Z.S., H.G., M.Ş.; Writing: G.O., Z.S., H.G.; Critical revision: H.G., M.Ş. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

10. Royse CF, Andrews DT, Newman SN, Stygall J, Williams Z, Pang J, et al. The influence of propofol or desflurane on postoperative cognitive dysfunction in patients undergoing coronary artery bypass surgery. Anaesthesia 2011;66:455−64. 11. Shoair OA, Grasso Ii MP, Lahaye LA, Daniel R, Biddle CJ, Slattum PW. Incidence and risk factors for postoperative cognitive dysfunction in older adults undergoing major noncardiac surgery: A prospective study. J Anaesthesiol Clin Pharmacol 2015;31:30−6. 12. Riis J, Lomholt B, Haxholdt O, Kehlet H, Valentin N, Danielsen U, et al. Immediate and long-term mental recovery from general versus epidural anesthesia in elderly patients. Acta Anaesthesiol Scand 1983;27:44−9.

14. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189−98. 15. Manos PJ, Wu R. The ten point clock test: a quick screen and grading method for cognitive impairment in medical and surgical patients. Int J Psychiatry Med 1994;24:229−44.

Orhun et al. Comparison of epidural analgesia combined with GA and GA for POCD in elderly patients 16. Moo LR, Slotnick SD, Tesoro MA, Zee DS, Hart J. Interlocking finger test: a bedside screen for parietal lobe dysfunction. J Neurol Neurosurg Psychiatry 2003;74:530−2. 17. Karakaş S, Kafadar H, Eski R. Wechsler Bellek Ölçeği geliştirilmiş formunun test-tekrar test güvenirliği. Türk Psikoloji Dergisi 1996;11:46−52. 18. Emek Savaş DD, Yerlikaya D, Yener GG. Validity, Reliability and Turkish Norm Values of the Clock Drawing Test for Two Different Scoring Systems. Turk J Neurol 2018;24:143−52. 19. Tumaç A. Normal deneklerde frontal hasarlara duyarlı bazı testlerde performansa yaş ve eğitimin etkisi. İstanbul Üniversitesi Sosyal Bilimler Enstitüsü Psikoloji Bölümü, Yüksek Lisans Tezi. 1997. 20. Höcker J, Stapelfeldt C, Leiendecker J, Meybohm P, Hanss R, Scholz J, et al. Postoperative neurocognitive dysfunction in elderly patients after xenon versus propofol anesthesia for major noncardiac surgery: a double-blinded randomized controlled pilot study. Anesthesiology 2009;110:1068−76. 21. Brown EN, Purdon PL. The aging brain and anesthesia. Curr Opin Anaesthesiol 2013;26:414−9. 22. Silbert B, Evered L, Scott DA, McMahon S, Choong P, Ames D, et al. Preexisting cognitive impairment is associated with postoperative cognitive dysfunction after hip joint replacement surgery. Anesthesiology 2015;122:1224−34. 23. Mason SE, Noel-Storr A, Ritchie CW. The impact of general and regional anesthesia on the incidence of post-operative cognitive dysfunction and post-operative delirium: a systematic review with meta-analysis. J Alzheimers Dis 2010;22:67−79. 24. Davis N, Lee M, Lin AY, Lynch L, Monteleone M, Falzon L, et al. Postoperative cognitive function following general versus regional anesthesia: a systematic review. J Neurosurg Anesthesiol 2014;26:369−76. 25. Subramaniyan S, Terrando N. Neuroinflammation and Perioperative Neurocognitive Disorders. Anesth Analg 2019;128:781−8. 26. Umholtz M, Nader ND. Anesthetic Immunomodulation of the Neuroinflammation in Postoperative Cognitive Dysfunction. Immunol Invest 2017;46:805−15.

27. Pan LF, Wang DX, Li J. Effects of different methods of anesthesia and analgesia on early postoperative cognitive dysfunction after non-cardiac surgery in the elderly. [Article in Chinese] Beijing Da Xue Xue Bao Yi Xue Ban 2006;38:510−4. 28. Chen C, Li M, Wang K, Shen J, Yang L, Bu X, et al. Protective effect of combined general and regional anesthesia on postoperative cognitive function in older arthroplasty patients. Int J Clin Exp Med 2017;10:15453−8. 29. Kristek G, Radoš I, Kristek D, Kapural L, Nešković N, Škiljić S, et al. Influence of postoperative analgesia on systemic inflammatory response and postoperative cognitive dysfunction after femoral fractures surgery: a randomized controlled trial. Reg Anesth Pain Med 2019;44:59−68. 30. Hovens IB, Schoemaker RG, van der Zee EA, Absalom AR, Heineman E, van Leeuwen BL. Postoperative cognitive dysfunction: Involvement of neuroinflammation and neuronal functioning. Brain Behav Immun 2014;38:202−10. 31. Chi H, Kawano T, Tamura T, Iwata H, Takahashi Y, Eguchi S, et al. Postoperative pain impairs subsequent performance on a spatial memory task via effects on N-methyl-D-aspartate receptor in aged rats. Life Sci 2013;93:986−93. 32. Alam A, Hana Z, Jin Z, Suen KC, Ma D. Surgery, neuroinflammation and cognitive impairment. EBioMedicine 2018:547−56. 33. Chan MT, Cheng BC, Lee TM, Gin T; CODA Trial Group. BIS-guided anesthesia decreases postoperative delirium and cognitive decline. J Neurosurg Anesthesiol 2013;25:33−42. 34. Kurnaz P, Sungur Z, Camci E, Sivrikoz N, Orhun G, Senturk M, et al. The effect of two different glycemic management protocols on postoperative cognitive dysfunction in coronary artery bypass surgery. Rev Bras Anestesiol 2017;67:258−65. 35. Şahan C, Sungur Z, Çamcı E, Sivrikoz N, Sayin Ö, Gurvit H, et al. Effects of cerebral oxygen changes during coronary bypass surgery on postoperative cognitive dysfunction in elderly patients: a pilot study. Rev Bras Anestesiol 2018;68:142−8.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

İleri yaş grubu hastalarda genel ve epidural anestezi ile yalnızca genel anestezi uygulamalarının nörokognitif fonksiyonlara etkilerinin karşılaştırılması Dr. Günseli Orhun,1 Dr. Zerrin Sungur,1 Dr. Kemalettin Koltka,1 Dr. Meltem Savran Karadeniz,1 Dr. Hacer Ayşen Yavru,1 Dr. Hakan Gürvit,2 Dr. Mert Şentürk1 1 2

İstanbul Üniversitesi İstanbul Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, İstanbul İstanbul Üniversitesi İstanbul Tıp Fakültesi, Nöroloji Anabilim Dalı, Davranış Nörolojisi ve Hareket Bozuklukları Birimi, İstanbul

AMAÇ: Ameliyat sonrası erken dönemde kognitif bozukluk yaşlı popülâsyonda sık görülür. Anestezi yönetimi ameliyat sonrası kognitif düşüşü etkileyebilir. Etkin analjezi, erken derlenme ve stres yanıtın modülasyonu nöroaksiyel blokların avantajlarıdır. Bu çalışmanın amacı, genel anestezi ve epidural analjezi ile kombine edilen genel anestezinin postoperatif kognitif bozukluk (PKB) için etkisini karşılaştırmaktır. Hipotezimiz genel anestezi (GA) ile birlikte nöroaksiyel bloğun, PKB önlenmesinde olumlu bir etkisi olacağıydı. GEREÇ VE YÖNTEM: Kalp cerrahisi dışında operasyona gelen 60 yaşın üstündeki hastalar bu ileriye yönelik randomize çalışmaya dâhil edildi ve hastalar iki gruba ayrıldı. Birinci gruptaki hastalara (GI) GA uygulandı; ikinci grupta (GII) ise epidural analjezi ile GA kombine edildi. Hastaların kognitif fonksiyonları, nöropsikolojik test bataryası kullanılarak ameliyattan bir hafta önce ve bir hafta sonra değerlendirildi. PKD, iki veya daha fazla testte bazal değerden bir standart sapma düşüş olarak tanımlandı. BULGULAR: Çalışmayı toplam 116 hasta tamamladı. GI’de GII’den anlamlı olarak yüksek olan maksimum ağrı skorları hariç (sırasıyla, 4.9±2.8’e karşılık 1.7±1.7; p<0.001) demografik ve operatif veriler gruplar arasında benzerdi. PKD insidansında gruplar arasında fark saptanmadı (GI’de %26 ve GII’de %24). Bellek performansı, görsel mekânsal fonksiyonlar ve dil beceri testleri GII’de GI’e göre anlamlı olarak yüksek bulundu. TARTIŞMA: Genel anestezi ve genel anestezi ile kombine epidural analjezi, abdominal cerrahi geçiren yaşlı hastalarda benzer PKD insidansı ile sonuçlandı. Bununla birlikte, kombine anestezi grubunda hafıza, dil becerileri ve görsel mekânsal fonksiyonların daha iyi korunduğu görüldü. Etkin ağrı kontrolü bazı alanlarda kognitif işlevlerin korunmasında katkı sağlayabilir durmaktadır. Anahtar sözcükler: Ameliyat sonrası ağrı; ileri yaş, kognitif bozukluk, genel anestezi, epidural analjezi, Ulus Travma Acil Cerrahi Derg 2020;26(1):30-36

doi: 10.14744/tjtes.2019.04135

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

ORIGIN A L A R T IC L E

The thiol-disulphide homeostasis in patients with acute pancreatitis and its relation with other blood parameters Fadime Güllü Ercan Haydar, M.D.,1* Yavuz Otal, M.D.,2# Alp Şener, M.D.,2† Gül Pamukçu Günaydın, M.D.,2† Ferhat İçme, M.D.,2# Tuğba Atmaca Temrel, M.D.,2‡ Pervin Baran, M.D.,3§ Özcan Erel, M.D.4¶ 1

Department of General Surgery, Atatürk Training and Research Hospital, Ankara-Turkey

Department of Emergency Medicine, Atatürk Training and Research Hospital, Ankara-Turkey

Department of Medical Biochemistry, Atatürk Training and Research Hospital, Ankara-Turkey

Department of Medical Biochemistry, Yıldırım Beyazıt University Faculty of Medicine, Ankara-Turkey

ABSTRACT BACKGROUND: Acute pancreatitis is a common disease seen in emergency departments because of abdominal pain. The present study aims to evaluate the relation between measurements of thiol-disulfide parameters in patients diagnosed with acute pancreatitis and other blood parameters. METHODS: A total of 56 (56%) patients, who were admitted to the emergency department, and 44 (44%) healthy volunteers participated in this study. A total of 100 samples were taken from the participants. Detailed blood samples were taken from the patients at the time of arrival at the hospital. The thiol-disulfide level in serum was examined using a brand new method that was developed by Erel and Neşelioğlu in the venous blood samples of the patients who were diagnosed with acute pancreatitis during the admission. The data were evaluated in the computer medium. RESULTS: Gallstones were defined as the etiology of AP in 41 patients (73.2%); in one patient, hypertriglyceridemia (1.7%); in four patients, alcohol use (7.1%), and idiopathic 10 patients (17.8%). While the blood thiol levels were low, the disulfide levels were high at a significant level. No statistically significant relations were detected between the amylase, lipase, neutrophil lymphocyte ratio (NLR), which are other blood parameters, and thiol-disulfide balance parameters. CONCLUSION: The disruption of the thiol-disulfide balance may play a role in the pathogenesis of acute pancreatitis. In acute pancreatitis, since the thiol level is decreased in the blood, administration of the complementary therapies for this thiol deficiency may contribute to the treatment of the disease. Keywords: Acute pancreatitis; oxidative stress; thiol-disulphide homeostasis.

INTRODUCTION Thiols, in other words, mercaptans, are in -SH group.[1] Generally, the plasma thiol pool is made up of thiols like albumin and low-molecular-weight cysteinylglycine, cysteine (Cys), homocysteine, glutathione and γ-glutamylcysteineprotein.[2]

Thiol-disulphide homeostasis is extremely important. Thiol/ Disulphide Ratio (TDR) is very important in the detoxification process. In previous studies, the findings showed that TDR had several effects on antioxidant protection, signal transduction, enzymatic regulation, apoptosis and cellular signal mechanisms.[3,4]

Cite this article as: Ercan Haydar FG, Otal Y, Şener A, Pamukçu Günaydın G, İçme F, Atmaca Temrel T, et al. The thiol-disulphide homeostasis in patients with acute pancreatitis and its relation with other blood parameters. Ulus Travma Acil Cerrahi Derg 2020;26:37-42. These authors currently work at: *Department of General Surgery, Ankara City Hospital; #Department of Emergency Medicine, Ankara City Hospital; † Department of Emergency Medicine, Yıldırım Beyazıt University Faculty of Medicine; ‡Department of Emergency Medicine, University of Health Sciences Faculty of Medicine; § Department of Medical Biochemistry, Ankara City Hospital; ¶Department of Medical Biochemistry, Yıldırım Beyazıt University Faculty of Medicine, all Ankara-Turkey

Address for correspondence: Fadime Güllü Ercan Haydar, M.D. Atatürk Eğitim ve Araştırma Hastanesi, Genel Cenrrahi Kliniği, Ankara, Turkey Tel: +90 312 - 291 25 25 E-mail: gulluercanhaydar@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):37-42 DOI: 10.14744/tjtes.2019.38969 Submitted: 02.10.2018 Accepted: 27.02.2019 Online: 31.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Ercan Haydar et al. The thiol-disulphide homeostasis in patients with AP and its relation with other blood parameters

In some diseases, the Thiol-Disulphide Ratio was examined. This ratio was measured unilaterally until 2014, and with the help of the new method that was developed by Erel and Neşelioglu,[5] it is, nowadays, possible to measure it bilaterally.[6] Acute pancreatitis (AP) is rare in clinical practice and its prevalence is approximately 80 per 100.000 people.[7,8] Severe AP occurs with persistent organ failure. The mortality and morbidity rates of severe AP are also high.[9,10] In recent years, a moderately severe AP has been reported as consisting of patients with transient organ failure or local/systemic complications without persistent organ failure.[9,11] In this study, we aim to examine the thiol/disulphide homeostasis parameters, which constitute homeostasis occurring in the maintenance of many physiological mechanisms that are necessary for organisms and patients with AP.

MATERIALS AND METHODS This study was approved by the ethical board of Yildirim Beyazit University (date: 03.12.2014, no: 208). A total of 56 (56%) patients, who were admitted to the emergency department, and 44 (44%) healthy volunteers participated in this study. A total of 100 samples were taken from the participants. AP diagnosis was considered as detection of two of the three necessary diagnosis criteria, which are (a) abdominal pain consistent with AP; (b) serum lipase or amylase levels being higher than three times the maximum limit of normal; and (c) the common findings obtained with abdominal imaging methods.[7] The exclusion criteria in the present study were patients who had chronic pancreatitis, malignant illnesses, renal failures, liver failures, heart failures, myocardial infarctions, rheumatic illnesses, psychiatric patients, and patients who had immunosuppressive disorders. The reason for this exclusion was that these diseases or conditions might affect the thiol/disulphide homeostasis. Detailed blood samples were taken from the patients at admission. The thiol-disulphide ratio was examined with a brand-new method that was developed by Erel and Neşelioğlu[5] at the admission of the patients who were diagnosed with acute pancreatitis.

Thiol-Disulphides Homeostasis Parameters Measurement Thiol/Disulphide Homeostasis tests were measured using an automated spectrophotometric method described by Erel and Neselioglu. For short, disulphide bonds were first reduced to form free functional thiol groups with sodium borohydride. Unused reductant sodium borohydride was consumed and removed with formaldehyde to prevent the reduction of DTNB (5,5’-dithiobis-(2-nitrobenzoic) acid), and all of the 38

thiol groups, including reduced and native thiol groups, were determined after the reaction with DTNB. Half of the difference between the total thiols and native thiols provides the dynamic disulphide amount. After the determination of native and total thiols, disulphide amounts, disulphide/total thiol percent ratios (SS/SH+SS), disulphide/native thiol percent ratios (SS/SH) and native thiol/total thiol percent ratios (SH/SH+SS) were calculated.[5]

Measurement of the IMA (Ischemia-Modified Albumin) Measurement of IMA levels was obtained using venous blood samples on admittance within one hour. Specimens were stored for 30 minutes at room temperature and then centrifuged at 3500 rpm for five minutes. Latter samples were transferred to Eppendorf tubes and stored at -80ºC until analysis. Albumin Cobalt Binding Test was used to detect the presence of Ischemia Modified Albumin (IMA). This test was performed by adding 50 mL 0.1% cobalt (II) chloride (CoCl2, 6H2O) (Sigma-Aldrich Chemie GmbH Riedstrasse 2, Steinheim, Germany) to the patient serum. After mixing, followed by 10 minutes of incubation to allow for albumin cobalt binding, 50 mL 1.5 mg/mL dithiothreitol was added. After mixing, followed by two minutes of incubation, 1.0 mL of a 0.9% sodium chloride solution was added to reduce the binding capacity. The blank was prepared similarly with distilled water instead of dithiothreitol. The absorbance of samples was measured at 470 nm using a spectrophotometer. The results were expressed as absorbance units (ABSU).[12]

Ferroxidase Measurement Ferroxidase levels were measured using the method described by Erel O.T. This method is automated, colorimetric and based on the enzymatic oxidation of ferrous ion to ferric ion. The results were expressed in units per liter serum.[13] Albumin, urea and creatinine tests were performed using Roche cobas c501 device using commercial kits of Roche. Neutrophil, lymphocyte and platelet levels were measured using the Sysmex hematology device.

Statistical Analyses The data were analyzed with the SPSS for Windows 16.0 Package Program. Firstly, descriptive statistics were given. The ratio comparisons in 2x2-eyed tables were performed with the Chi-Square test. The normality analysis of the continuous data was carried out with the Kolmogorov-Smirnov Test, and it was accepted as a result of the test that the data with a value of p<0.05 were not distributed normally. The Independent Samples t-test was employed for the data that showed the normal distribution in the comparisons made between two groups, and the Mann-Whitney U-test was employed for the data that did not show normal distribuUlus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Ercan Haydar et al. The thiol-disulphide homeostasis in patients with AP and its relation with other blood parameters

The AP etiology was gallstones in 41 of the patients (73.2%), hypertriglyceridemia in one patient (1.7%), alcohol use in four patients (7.1%), and was idiopathic in 10 patients (17.8%).

tion. The Spearman Correlation Test was employed for the analysis in the analysis of the data that were not normally distributed, and the Pearson Correlation Test was employed in the normally distributed data. The P-value was employed for statistical significance, and the results that were p<0.05 were considered to be statistically significant.

The in-hospital mortality was determined as 1.8% (1 case) in the Study Group. The 28-day mortality was also determined to be 1.8% (1 case). The mean hospitalization was determined as five days (min-max: 1–41; IQR:3) (6.05 days on average).

As a result of the correlation analyses, no parameters were determined that had a correlation with the hospitalization time at a significant level. NLR had a weak correlation with amylase (p=0.018, rho: 0.333) and lipase (p=0.031, rho: 0.306). No relations were detected between the thiol/disulphide homeostasis parameters and amylase and/or lipase.

According to the Balthazar Classification and the CTSI (Computed Tomography Severity Index), 32 patients in the Study Group had AP, 32 had mild AP (0-4 points), 20 had moderatesevere AP (4–6 points), and four patient had severe AP (7–10 points).[14] The hematologic and biochemical parameters, thiol/disulphide homeostasis parameters, IMA and ferroxidase average and median values and the statistical analysis of the differences of the Patient and Control Group are given in Table 1. The findings showed that all of the creatinine, neutrophil, neutrophil/lymphocyte ratio, thiol/disulphide homeostasis parameters, IMA and ferroxidase values were different at a statistically significant level between the groups (Figs. 1–3). In the Patient Group, the neutrophil, neutrophil/lymphocyte ratio, disulphide and IMA were higher at a significant level and the creatinine, NT, TT, index-1, and ferroxidase were lower at a significant level (Table 1).

RESULTS The study group consisted of 56 (56%) patients, and 44 (44%) healthy volunteers applying to the emergency department. A total of 100 samples were taken from the participants. The mean age of the Control Group was 64 (Min-max: 21–80), and the mean age of the Study Group was found to be 57 (Min-max: 18–92). There were no differences between the two groups concerning age distribution at a statistically significant level. In the Control Group, the male gender was 38.6%, and in the Study Group, it was 39.3%. This difference was not found to be statistically significant (Table 1).

Table 1. Biochemical and hematological parameters in patient and control groups

Acute pancreatit patient / Control group

Control

p Patient

Mean SD Min Med Max 95% CI / Mean SD Min Med Max 95% CI*/ IQR** IQR** *

Albumin*

4.38 0.36 3.74 4.32 5.06 4.27–4.49 4.31 0.42 3.4 4.31 5.22 4.26–4.47 0.371

Ure

35.2 11.8 18.2 34 66.7

19.0 32.1 14.7 13 27.4 82

12.0

0.066

Creatinin**

0.9 0.16 0.56 0.95 1.28

0.22

0.9 0.81 0.3 0.8 6.5

0.32

0.011

Neutrophil**

4645 1811 2210 4330 10100

2088

8996 4156 2700 8450 24100

3880

<0.001

Lymphocyte*

2068 1053 300 1885 6700 1748–2388 1746 1013 200 1600 5000 1465–1986 0.124

Platelets* (x103) 269 74 88 259 431 246–291 252 81 111 235 456 235–281 0.295 NLR**

2.92 2.3 0.45 2.23 12.94

1.7

7.33 5.95 1.6 5.77 31

7.19 <0.001

Native Thiol

436.4 65.2 278.4 436.2 578.3 416.6–456.2 352.1 109.1 93.5 342.6 710 332.9–392.2 <0.001

Disulphide*

16.22 7.41 3.85 15.38 33 13.97–18.47 21.39 14.55 0.45 19.58 71.1 17.43–25.75 0.024

Total Thiol

468.8 65.1 305.5 470.9 607.3 449.0–488.6 394.9 108.2 96.7 389.7 735.7 376.9–434.6 <0.001

Index1**

0.038 0.018 0.008 0.039 0.073

0.026

0.068 0.058 0.001 0.055 0.273

0.039

0.005

Index2

0.035 0.016 0.008 0.036 0.064

0.022

0.056 0.039 0.001 0.049 0.177

0.032

0.005

Index3**

0.930 0.031 0.872 0.929 0.984

0.044

0.888 0.079 0.647 0.901 0.998

0.064

0.005

IMA

66.7 9.4 50.8 70.5 84

18.1

73.7 9.3 35.8 74 97

6.8

<0.001

Ferroksidaz**

567 185.8 309.7 514.6 1054.1

255.1

461.5 224.2 40 472.5 1247.7

184

0.025

*Independent Samples-t test; Mean±SD ve 95% CI. **Mann Whitnet-U test; Median (Min-Max) ve IQR. NLR: Neutrophil lymphocyte ratio; IMA: Ischemia-modified albumin; SD: Standard deviation; Min: Minimum; Max: Maximum; CI: Confidence interval; IQR: Interquartile interval. Index1: disulphide/native thiol. Index2: disulphide /total thiol. Index3: native thiol/total thiol.

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signal transduction, regulation of enzymatic activity, as well as transcription factors and cellular signaling mechanisms.[3,4] Since thiols have continuous interaction with almost all of the physiological oxidants, they are essential antioxidant buffers. [15,16] Thiol protein groups constitute a significant antioxidant group and are responsible for 52.9% of the total serum antioxidant capacity in healthy people.[17] A new and automated testing system was proposed by Erel and Neselioglu[5] to determine the dynamic thiol/disulphide homeostasis. Total serum thiol and native thiol levels are measured; and disulphide concentrations are computed in this method. This test shows the changes in favor of the thiol or disulphide.

800

Total thiol (µmol/L)

600

400

200

0 Control

Acute pancreatit

Figure 1. The total thiol distribution in the patient and control group.

Negative thiol (µmol/L)

800

600

400

200

0 Control

Acute pancreatit

Figure 2. The native thiol distribution in the patient and control group.

Disulphide (µmol/L)

0 Control

Acute pancreatit

Figure 3. The disulphide distribution in the patient and control group.

DISCUSSION The dynamic thiol/disulphide homeostasis has a crucial significance in detoxification, antioxidant protection, apoptosis, 40

Acute pancreatitis is a fascinating disease. The two most common etiologies of acute pancreatitis are gallstones and excessive alcohol consumption. The diagnosis of acute pancreatitis is made with a combination of history, physical examination, computed tomography scan, and laboratory evaluation. Differentiating patients who will have a benign course of their pancreatitis from patients who will have severe pancreatitis is challenging to the clinician. Releasing active pancreatic enzymes into the bloodstream initiates an inflammatory cascade, which is involved in stimulating the production of many inflammatory cytokines, including interleukins and tumor necrosis factor-α. This cytokine storm can be determined by several serum markers. C-reactive protein (CRP) is the most widely studied and used serum marker to assess the severity of AP. Aside from CRP, many other acute-phase reactants and inflammatory markers, including cytokines, have been studied to assess the severity of AP. Recently, several studies investigated the thiol-disulphide and IMA levels in disorders in which oxidative stress plays an important role in the pathogenesis, including diabetes, cirrhosis, end-stage renal disease, sepsis, and inflammatory bowel disease. Ischemia and oxidative stress are the major determinants of forming IMA, and an increase in serum IMA levels was demonstrated in ischemic disorders and in disorders that oxidative stress contributes to its pathogenesis. Oxidative stress and the production of free radicals are responsible for the progression of pancreatic inflammation, and triggering the generation of inflammatory cytokines is the key event in the pathogenesis of acute pancreatitis.[18] We concluded that thiol-disulphide levels decreased as oxidative stress increased in acute pancreatitis. This study aims to compare the thiol-disulphide homeostasis and other blood parameters levels of patients with AP and healthy controls, and to investigate thiol-disulphide homeostasis as a marker of disease severity. In the present study, disulphide/total thiol and disulphide/native thiol rates increased in favor of disulphide at a significant level. However, the native thiol levels decreased. The thiol level, native thiol level, and native thiol/total thiol percent ratios were lower. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Ercan Haydar et al. The thiol-disulphide homeostasis in patients with AP and its relation with other blood parameters

The findings showed that in the thiol/disulphide homeostasis tests that the homeostasis shifted towards the thiol or disulphide side. When the novel method was used, low thiol/ disulphide homeostasis was detected in some clinical settings (such as hyperemesis gravidarum, acute myocardial infarction, non-ST elevation myocardial infarction, and Type I Diabetes Mellitus).[15,19–21] Reduced glutathione is the basic non-protein thiol in the cells of all mammals and constitutes a significant antioxidant. In animal AP models, its decrease in pancreatic tissue was shown in previous studies.[22–24] In thiol measurements, these studies employed pancreatic tissue; however, in our study, the thiol/ disulphide homeostasis parameters were measured in serum with a novel, easy and full-automatic method in AP patients. The low-molecular-weight thiols and disulphides were evaluated in a study conducted on animal models with AP by Moreno et al.,[25] who considered disulphide stress as a specific OS type that was associated with mixed disulphides, especially protein cysteinylation, and oxidation of thiols like gamma-glutamylcysteine, cysteine, and homocysteine. However, they did not report any glutathione oxidation or changes in protein glutathionylation. It was also determined that reduced glutathione level reduced in the pancreatic tissue of rats with AP.[25] Thiol levels were investigated in studies conducted on animals with pancreatitis, and the thiol-disulphide homeostasis parameters have been examined in humans for the past few years. In our study, the disulphide/total thiol and disulphide/ native the thiol rates increased at a significant level in favor of disulphide. However, the native thiol and total thiol levels decreased. The thiol-disulphide homeostasis increased in favor of disulphide. Similar results were obtained in a study that was conducted before ours.[26] In our study, we obtained similar results with different tests that showed oxidative stress in tissues. There are several other studies that examined plasma oxidative stress.[25,27,28] We determined that this homeostasis shifted in favor of disulphide by examining the thiol-disulphide homeostasis in AP. Among OS markers, there are ischemia-modified albumin, protein carbonyls and superoxide dismutase, which increase among AP in different trials.[27–29] In a recent meta-analysis study, it was reported that antioxidant therapy had possible benefits for AP, which might be considered as a proof that decreases in the antioxidant levels occurring in AP pathogenesis.[30,31] The neutrophil lymphocyte ratio, which is examined in the serum, may be considered as an indirect indicator of the immune response capacity of the host. The reason why NLR indicates that the prognosis is bad may be due to that tumors make metastasis through cytokines and chemokines, and that the mechanism in which the dominance of neutrophils may suppress the cytotoxic T cells. In the first 48 hours, the increase in the NLR is related to severe acute pancreatitis and Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

is an independent negative prognostic marker in AP.[32] In the present study, we could not detect any statistically significant relation between the blood thiol-disulphide homeostasis parameters and serum NLR. The findings suggest the thiol/disulphide homeostasis deficiency may have a role in the AP pathogenesis. Complementing with thiol compounds like N-Acetyl Cysteine (NAC) may be a target for AP therapy. NAC is considered as a free radical collector and stimulates the glutathione synthesis.[30,31] In the study, the findings suggest that mixed antioxidant supplementation with NAC could reduce the hospital stay and the rate of complications in AP patients.[33,34]

Conclusion The disruption of thiol-disulphide homeostasis may have a role in the pathogenesis of acute pancreatitis. Since the thiol level is decreased, administering complementary treatment for thiol deficiency may contribute to the healing of the disease. Ethics Committee Approval: Approved by the local ethics committee (date: 03.12.2014, no: 208). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: F.G.E.H., Y.O.; Design: G.P.G., A.Ş.; Supervision: Ö.E.; Fundings: Ö.E.; Materials: F.G.E.H., Y.O.; Data: F.G.E.H., Y.O.; Analysis: F.G.E.H., Y.O., A.Ş.; Literature search: T.A.T., P.B.; Writing: F.G.E.H., Y.O. ; Critical revision: F.G.E.H., Y.O., F.İ. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Sen CK, Packer L.Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr 2000;72:653–69. 2. Turell L, Radi R, Alvarez B. The thiol pool in human plasma: the central contribution of albumin to redox processes. Free Radic Biol Med 2013;65:244−53. 3. Biswas S, Chida AS, Rahman I. Redox modifications of protein-thiols: emerging roles in cell signaling. Biochem Pharmacol 2006;71:551−64. 4. Circu ML, Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med 2010;48:749−62. 5. Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem 2014;47:326−32. 6. Ellman G, Lysko H. A precise method for the determination of whole blood and plasma sulfhydryl groups. Anal Biochem 1979;93:98−102. 7. Tenner S, Baillie J, DeWitt J, Vege SS; American College of Gastroenterology. American College of Gastroenterology guideline management of acute pancreatitis. Am J Gastroenterol 2013;108:1400−15. 8. Hamada T, Yasunaga H, Nakai Y, Isayama H, Horiguchi H, Fushimi K, et al. Japanese severity score for acute pancreatitis well predicts in-hospital mortality: a nationwide survey of 17,901 cases. J Gastroenterol 2013;48:1384−91. 9. Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and defini-

Ercan Haydar et al. The thiol-disulphide homeostasis in patients with AP and its relation with other blood parameters tions by international consensus. Gut 2013;62:102−11. 10. Chen Y, Ke L, Tong Z, Li W, Li J. Association between severity and the determinant-based classification, Atlanta 2012 and Atlanta 1992, in acute pancreatitis: a clinical retrospective study. Medicine (Baltimore) 2015;94:e638. 11. Vege SS, Gardner TB, Chari ST, Munukuti P, Pearson RK, Clain JE, et al. Low mortality and high morbidity in severe acute pancreatitis without organ failure: a case for revising the Atlanta classification to include “moderately severe acute pancreatitis”.Am J Gastroenterol 2009;104:710−5. 12. Bar-Or D, Lau E, Winkler JV. A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia-a preliminary report. J Emerg Med 2000;19:311−5. 13. Erel O. Automated measurement of serum ferroxidase activity. Clin Chem 1998;44:2313−9. 14. Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH. Acute pancreatitis: value of CT in establishing prognosis. Radiology 1990;174:331−6. 15. Ergin M, Cendek BD, Neselioglu S, Avsar AF, Erel O. Dynamic thiol-disulfide homeostasis in hyperemesis gravidarum. J Perinatol 2015;35:789−92. 16. Otal Y, Demircan S, Şener A, Alışık M, Tanrıverdi F, Ercan Haydar FG, et al. Acute Renal Failure and Thiol-Disulfide Homeostasis. J Nephrol Ther 2018;8:312. 17. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004;37:277−85. 18. Sahin A, Turkoglu S, Tunc N, Duzenci D, Solmaz OA, Bahcecioglu IH, et al. Is ischemia-modified albumin a reliable tool for the assessment of acute pancreatitis? Ther Clin Risk Manag 2018;14:627−35. 19. Kundi H, Ates I, Kiziltunc E, Cetin M, Cicekcioglu H, Neselioglu S, et al. A novel oxidative stress marker in acute myocardial infarction; thiol/ disulphide homeostasis. Am J Emerg Med 2015;33:1567−71. 20. Kundi H, Erel Ö, Balun A, Çiçekçioğlu H, Cetin M, Kiziltunç E, et al. Association of thiol/disulfide ratio with syntax score in patients with NSTEMI. Scand Cardiovasc J 2015;49:95−100. 21. Ates I, Kaplan M, Yuksel M, Mese D, Alisik M, Erel Ö, et al. Determination of thiol/disulphide homeostasis in type 1 diabetes mellitus and the factors associated with thiol oxidation. Endocrine 2016;51:47−51. 22. Perez S, Pereda J, Sabater L, Sastre J. Redox signaling in acute pancreati-

tis. Redox Biol 2015;5:1−14. 23. Dabrowski A, Chwiećko M. Oxygen radicals mediate depletion of pancreatic sulfliydryl compounds in rats with cerulein-induced acute pancreatitis. Digestion 1990:47:15−9. 24. Schoenberg MH, Büchler M, Gaspar M, Stinner A, Younes M, Melzner I, et al. Oxygen free radicals in acute pancreatitis of the rat. Gut 1990;31:1138−43. 25. Moreno ML, Escobar J, Izquierdo-Álvarez A, Gil A, Pérez S, Pereda J, et al. Disulfide stress: a novel type of oxidative stress in acute pancreatitis. Free Radic Biol Med 2014;70:265−77. 26. Köseoğlu H, Alışık M, Başaran M, Tayfur Yürekli Ö, Solakoğlu T, Tahtacı M, et al. Dynamic thiol/disulphide homeostasis in acute pancreatitis. Turk J Gastroenterol 2018;29:348−53. 27. Dur A, Kocaman O, Kocyiğit A, Turkdogan KA, Sonmez E, Keskin S, et al. Oxidative status and lymphocyte DNA damage in patients with acute pancreatitis and its relationship with severity of acute pancreatitis. Turk J Gastroenterol 2016;21:68−72. 28. Baser H, Can U, Karasoy D, Ay AS, Baser S, Yerlikaya FH, et al. Evaluation of oxidant/anti-oxidants status in patients with mild acute -pancreatitis. Acta Gastroenterol Belg 2016;79:23−8. 29. Winterbourn CC, Bonham MJ, Buss H, Abu-Zidan FM, Windsor JA. Elevated protein carbonyls as plasma markers of oxidative stress in acute pancreatitis. Pancreatology 2003;3:375−82. 30. Thareja S, Bhardwaj P, Sateesh J, Saraya A. Variations in the levels of oxidative stress and antioxidants during early acute pancreatitis. Trop Gastroenterol 2009;30:26−31. 31. Jeurnink SM, Nijs MM, Prins HA, Greving JP, Siersema PD. Antioxidants as a treatment for acute pancreatitis: A meta-analysis. Pancreatology 2015;15:203−8. 32. Binnetoğlu E, Akbal E, Güneş F, Sen H. The prognostic value of neutrophil-lymphocyte ratio in acute pancreatitis is controversial. J Gastrointest Surg 2014;18:885. 33. Du BQ, Yang YM, Chen YH, Liu XB, Mai G. N-acetylcysteine improves pancreatic microcirculation and alleviates the severity of acute necrotizing pancreatitis. Gut Liver 2013;7:357−62. 34. Katsinelos P, Kountouras J, Paroutoglou G, Beltsis A, Mimidis K, Zavos C. Intravenous N-acetylcysteine does not prevent post-ERCP pancreatitis. Gastrointest Endosc 2005;62:105−11.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut pankreatitli hastalarda tiyol-disülfit dengesi ve diğer kan parametreleri ile ilişkisi Dr. Fadime Güllü Ercan Haydar,1 Dr. Yavuz Otal,2 Dr. Alp Şener,2 Dr. Gül Pamukçu Günaydın,2 Dr. Ferhat İçme,2 Dr. Tuğba Atmaca Temrel,2 Dr. Pervin Baran,3 Dr. Özcan Erel4 Atatürk Eğitim ve Araştırma Hastenisi, Genel Cerrahi Kliniği, Ankara Atatürk Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, Ankara 3 Atatürk Eğitim ve Araştırma Hastanesi,Tıbbi Biyokimya Kliniği, Ankara 4 Yıldırım Beyazıt Üniversitesi Tıp Fakültesi, Tıbbi Biyokimya Anabilim Dalı, Ankara 1 2

AMAÇ: Akut pankreatit (AP) karın ağrısı nedeniyle acil serviste sıklıkla görülen bir hastalıktır. Bu çalışma AP tanısı konulan hastalarda, kanda tiyoldisülfit parametrelerinin ölçümü ve diğer kan parametreleri ile ilişkisinin değerlendirilmesi amaçlandı. GEREÇ VE YÖNTEM: Çalışmaya acil servise başvuran 56 (%56) hasta ve 44 (%44) sağlıklı gönüllü olmak üzere toplam 100 örnek alındı. Hastalardan geliş anında detaylı kan örnekleri alındı. Akut pankreatit tanısı konan hastaların başvurusu sırasında ki venöz kan örneklerinden Erel ve Neşelioğlu tarafından geliştirilen yepyeni bir yöntemle serumda tiyol-disülfide düzeyi çalışıldı. Veriler bilgisayar ortamında değerlendirildi. BULGULAR: Akut pankreatitin etiyolojisi 41 hastada (%73.2) safra taşı, bir hastada (%1.7) hipertrigliseridemi, dört hastada (% 7.1) alkol kullanımı ve 10 hastada (%17.8) idiyopatik idi. Kan tiyol düzeyleri düşük iken, disülfide düzeyleri anlamlı derecede yüksekti. Diğer kan parametreleri olan amilaz, lipaz, NLR (nötrofil lenfosit oranı) ile tiyol-disülfide dengesi parametreleri arasında istatistiki açıdan anlamlı fark bulunamadı. TARTIŞMA: Akut pankreatit de patogenezde tiyol-disülfit dengesinin bozulması rol oynayabilir. AP’de kanda tiyol düzeyi azaldığından bu tiyol eksikliğini tamamlayıcı tedavilerin verilmesi hastalığın iyileşmesine katkıda bulunabilir. Anahtar sözcükler: Akut pankreatit; oksidatif stres; tiyol-disülfid dengesi. Ulus Travma Acil Cerrahi Derg 2020;26(1):37-42

doi: 10.14744/tjtes.2019.38969

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

ORIGIN A L A R T IC L E

Analysis of risk factors of mortality in abdominal trauma Fatih Gönültaş, M.D.,1 Koray Kutlutürk, M.D.,1 Ali Fuat Kaan Gök, M.D.,2 Bora Barut, M.D.,1 Tevfik Tolga Şahin, M.D.,1 Sezai Yılmaz, M.D.1 1

Department of Surgery, İnönü University Faculty of Medicine, Malatya-Turkey

Department of Surgery, İstanbul University İstanbul Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: The present study aims to analyze blunt and penetrating abdominal traumas that were evaluated in our emergency department, the treatment approaches and risk factors of mortality. METHODS: Six hundred and sixty-four patients were admitted to our emergency department for surgical evaluation for trauma between January 2009 and April 2019. After the exclusion of dead on arrival, patients with missing data and patients without abdominal trauma were excluded from this study. Hundred and thirteen patients with abdominal trauma admitted to our department were evaluated in this study. Demographic, clinical, prognostic and mortality related factors were retrospectively analyzed. RESULTS: The mean age of the patients was 36.08±16.1 years. There were 90 male patients. Eighty patients (70.8%) had blunt abdominal trauma (BAT). Twenty-eight patients (24.7%) had isolated liver and two patients (1.7%) had isolated spleen injury. Combined liver and spleen injury was found in two patients (1.7%). Twenty-two (19.4%) patients had mortality. Causes of mortality were an irreversible hemorrhagic shock (40.9%) and central nervous system (13.6%) injuries. BAT was the main mechanism of injury in patients with mortality (86.4% versus 67%; p<0.001). The frequency of retroperitoneal injury was significantly higher in patients with mortality (50% versus 16.5%, p<0.001). The frequency of extra-abdominal injury in patients with mortality was higher (68.1% versus 49.4%; p=0.047). Mean arterial pressure at admission was found to be significantly lower in patients with mortality (67±26.8 mmHg versus 84.3±17 mmHg; p=0.02). The number of packed erythrocytes transfused in patients with mortality was higher (8.8±8.6 versus 3.3±5.9 units; p=0.047). Mean international normalized ratio (INR) was significantly higher in patients with mortality (4.3±7.1 versus 2.7±4; p=0.016). Mean lactate dehydrogenase level was higher in patients with mortality (1685.7±333.8 versus 675.8±565.3 IU/mL; p<0.001). Mean alanine aminotransferase (ALT) was significantly higher in patients with mortality (430±619 versus 244±448 IU/mL; p<0.001). Mean alkaline phosphatase (ALP) level in patients with mortality was higher (76.9±72.8 versus 67.3±27.8 IU/mL; p=0.003). The presence of retroperitoneal injury and ALT >516 IU/mL were independent risk factors o mortality. CONCLUSION: We have found certain laboratory variables to increase in patients with mortality. These are related to the severity of trauma. Retroperitoneal injury and increased ALT levels being risk factors of mortality is the most important finding of this study. Our results can guide other centers in the evaluation of trauma patients, and high-risk groups can be identified. Keywords: Abdominal trauma; blunt abdominal trauma; mortality; penetrating abdominal trauma.

INTRODUCTION The abdominal cavity is the third most common site affected in trauma.[1] The abdominal region is affected in 1/3rd of the cases. One-fourth of the cases undergo explorative surgery for evaluation of the abdominal injury.[2] Although the majority of the abdominal trauma requires conservative manage-

ment, and only a small fraction requires surgery, the overall mortality rate ranges from 10–36%.[2–5] In Turkey, approximately 400000 patients are victims of traumatic injury, including accidents, assault, vehicle collisions and penetrating trauma. Aldemir et al. have reported the mortality rate of 10.1% in 1048 penetrating abdominal trauma

Cite this article as: Gönültaş F, Kutlutürk K, Gök AFK, Barut B, Şahin TT, Yılmaz S. Analysis of risk factors of mortality in abdominal trauma. Ulus Travma Acil Cerrahi Derg 2020;26:43-49. Address for correspondence: Fatih Gönültaş, M.D. İnönü Üniversitesi Turgut Özal Tıp Merkezi, Genel Cerrahi Anabilim Dalı, 44040 Malatya, Turkey Tel: +90 422 - 341 06 60 / 3701 E-mail: fatnih44@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):43-49 DOI: 10.14744/tjtes.2019.12147 Submitted: 12.09.2019 Accepted: 23.09.2019 Online: 31.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Gönültaş et al. Analysis of risk factors of mortality in abdominal trauma

victims.[4] Tekesin et al.[6] have analyzed 138.352 trauma victims, which is the largest cohort that has been reported so far. Fifty-five percent of the patients have blunt abdominal trauma, whereas 10.1% were penetrating trauma victims. The reported mortality rates were 0.16%.[6] Therefore, it is a major cause of death, especially among young males; and a public health problem in Turkey. In Turkey, there are very few centers that are focused on the management trauma patients. Therefore, throughout the country, each surgical clinic deals with trauma victims in their region. High volume center should share their experiences regarding the management of trauma patients to guide other low volume hospitals for the management of abdominal trauma. Management of abdominal trauma is a challenging task for there are blunt, penetrating and mixed mechanisms involving the development. The reported incidence of blunt abdominal trauma is 90%.[7] Ozpek et al.[8] have reported the most frequent causes of blunt abdominal trauma as motor vehicle accidents in 62% and fall from heights as 27% of the cases. Mortality is seen in nearly 10% of the cases.[8] The causes of mortality are mainly occult extra-abdominal injuries involving the central nervous system and thorax, which was present in 96% of the cases reported by Pimentel et al.[3] On the other hand, penetrating abdominal trauma, including gunshot wounds, are more common in regions where terrorism or crime levels, including interpersonal conflicts, are high.[9] The mortality rate in penetrating abdominal trauma is around 2–13%.[2] The causes of mortality in penetrating abdominal trauma are either immediate death at the crime scene due to exsanguination or septic complications and multiorgan failure in the late postoperative period.[2,9] Iflazoglu et al.[10] have analyzed 120 gunshot wounds and the reported mortality rate as 39%. Risk factors of mortality were a shock at admission, the number of injured organs and the number of transfusions required to the patient.[10] In the present study, we evaluated 664 trauma victims that were admitted to our emergency department with various sites and severity of trauma. We evaluated patients with abdominal trauma to evaluate the causes and risk factors of mortality to develop a management protocol and to guide other centers in the region.

MATERIALS AND METHODS Patients Included in This Study Between January 2009 and April 2019, 664 patients that were admitted to Inonu University Turgut Ozal Medical Center Department of Emergency medicine with suspected abdominal trauma and admitted for follow-up by the surgical team have been analyzed retrospectively. The patients with an intra-abdominal injury that were either operated or conservatively followed by the surgical team were included in this study. The patients who were declared dead upon emergency 44

department admission, patients with inadequate clinical and operative data, and patients without abdominal trauma at the end of the follow-up period were excluded from this study. In total, 113 patients who had intra-abdominal injury that were operated or conservatively followed by the surgical team were included. The characteristics of the cohort analyzed in this study are summarized in Table 1. The patients operated at the end of a follow-up period were included in the operative management group. The patients that have not been operated have been included in the conservative management group. Due to the retrospective nature of this study, we did not apply for approval of the local institutional review board since patient data were only retrospectively analyzed.

Study Parameters The patient database of Inonu University Turgut Ozal Medical Center was retrospectively analyzed. Demographic Data, mode of injury (Blunt, Penetrating, mixed), duration of hosTable 1. Characteristic of the patients in the study Patient characteristics Gender (Male/Female)

90/23

Age (years), mean±SD

36.08±16.1

Duration of hospitalization (days), mean±SD

21.4±52.9

Trauma type, n (%)

Blunt

80 (70.8)

Penetrating

29 (25.7)

Mixed

4 (3.5)

Mortality, n (%)

22 (19.4)

HR on admission (beats/min) mean±range

91.6±22.6

Management, n (%)

Conservative

19 (16.8)

Operative

94 (83.2)

Intraoperative findings, n (%)

Liver

Spleen

87 (77) 23 (20.3)

Bowel

9 (8)

Colon

9 (8)

Mesentery

Retroperitoneal

Diaphragm

Adrenal

Extra abdominal

Mean arterial pressure (mmHg), mean±range

8 (7) 26 (23) 14 (12.4) 10 (9) 68 (60.2) 81.1±20.2

Transfusion ES unit, mean±SD

4.4±6.9

Angiographic intervention, n (%)

3 (2.2)

All continuous variables are expressed as mean±SD and categorical variables are expressed as number and percentage of the study population. SD: Standard deviation; HR: Heart rate; ES: Erythrocyte suspension.

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pitalization, treatment of choice (conservative vs operative), outcome of the patient and the causes of mortality, organ(s) that were injured, heart rate and mean arterial pressure on admission, laboratory data, including complete blood count, biochemistry in preoperative period, number of erythrocyte suspension that was transfused, were all included and analyzed in this study. The continuous and discrete data were further analyzed to find risk factors for mortality in the study cohort. Therefore, the study cohort was divided into two groups consisting of patients with (n=22) and without mortality (n=91).

Classification of the Injuries in the Abdominal and Extra-Abdominal Regions Solid-organ injuries, hollow organ injuries, injuries in the small bowel and colon mesentery, injuries to the retroperitoneal organs, adrenal injuries and encountered diaphragmatic ruptures were all classified as intra-abdominal injury. Injuries in the musculoskeletal system, such as the vertebrae, costae, and lungs, extremity, abdominal musculature, pelvic rim, injuries to the central nervous system, were considered as extra-abdominal injury.

Statistical Analysis The continuous variables were analyzed with the Kolmogorov-Smirnoff Test for evaluation of the distribution of normality. Since all the variables were normally distributed, the continuous variable was expressed as mean and standard deviation. The categorical data were expressed as the percentage of the study population. The dependent and independent variables were compared using the Student t-test. Multiple variables were analyzed by ANOVA for any difference concerning the variables. Any p-value less than 0.05 was considered as statistically significant. Initially, ROC analysis was performed on continuous variables to determine a cut-off value, determining the 90% sensitivity and specificity for the determination of mortality. Following ROC analysis, univariate and multivariate logistic regression analysis was performed to determine independent risk factors that determine the mortality of the patients. All statistical analyses were performed using the Statistical Program for Social Sciences software package 20 (SPSSv20, IBM, USA).

RESULTS Characteristics of the Patients Hundred and thirteen patients with abdominal trauma and various intra-abdominal lesions were included in this study. The male to female ratio was 90/23. The mean age of the patients was 36.08±16.1 years. The distribution of the trauma type was blunt trauma in 80 patients (70.8%), penetrating trauma in 29 patients (25.7%) Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

and mixed trauma in 4 (3.5%). Nineteen patients (16.8%) were treated expectantly. The characteristics and the total number of patients with various organ injuries are summarized in Table1. Twenty-eight patients (24.7%) had isolated liver injury. Two patients (1.7%) had isolated spleen injury. Combined liver and spleen injury was found in two patients (1.7%). The rest of the cohort had combined bowel, solid organ injuries and retroperitoneal injuries accompanied by extra-abdominal injuries, such as injuries to the musculoskeletal system, central nervous system, diaphragmatic injury. The site of extra-abdominal injury is summarized in Table 2. Twenty-two (19.4%) patients had mortality. The causes of mortality in this study were central nervous system complications in three patients (13.6%), intraoperative loss due to hemorrhagic shock in nine patients (40.9%), septic complications in nine patients (40.9%), and unknown in one patient (4.6%). The demographic, clinical and laboratory values of the patients with and without mortality are summarized in Table 3 and 4. The following section will analyze the study parameters among the patients with and without mortality.

The Demographic, Clinical and Laboratory Characteristics of the Patients with and without Mortality The demographic, clinical, operative and laboratory data of the patients are summarized in Table 3 and 4. Briefly, the mean age of the patients with and without mortality was 37.9±20.5 and 35.6±14.9 years, respectively (p=0.03). Gender did not have a significant impact on the mortality of the patients. Blunt abdominal trauma was the main mechanism of injury in 19 patients (86.4%) with mortality, whereas it was observed in 61 (67%) in patients without mortality. This difference was statistically significant (p<0.001). The frequency of retroperitoneal injury was significantly higher in patients with mortality when compared with patients without mortality [n=11 (50%) versus n=15 (16.5%); p<0.001]. Similarly, the frequency of extra-abdominal injury in patients with and without mortality was 68.1% (n=15 patients) and 49.4% (n=45 patients), Table 2. The distribution of extra abdominal injuries in the study [No injury: 44 (38.9%)] Extra-abdominal injuries

Thorax

23.9

Central nervous system

13.3

Extremity

11 9.7

Vertebra

3 2.7

Others

13 11.5

*This group includes the pelvic rim, abdominal musculature, renal and ovarian injury.

Gönültaş et al. Analysis of risk factors of mortality in abdominal trauma

Table 3. The demographic and clinical characteristics of the study groups in the study

Mortality

Yes (n=22)

No (n=91)

Gender (Male/Female)

17/5

73/18

=0.5

Age (years), mean±SD

37.9±20.5

35.6±14.9

=0.03

Duration of hospitalization (days), mean±SD

8.4±12.9

35.6±14.9

=0.2

Trauma type, n (%)

Blunt

19 (86.4)

61 (67)

Penetrating

3 (13.6)

26 (28.6)

Mixed

4 (4.4)

94.8±28.9

90.8±20.9

HR on admission (beats/min), mean±range

Management, n (%)

Conservative

4 (18.2)

15 (16.5)

Operative

18 (81.8)

76 (83.5)

<0.001

=0.15 =0.7

Intraoperative findings, n (%)

Liver

17 (77.3)

70 (76.9)

=0.9

Spleen

4 (18.2)

19 (20.9)

=0.5

Bowel

2 (9.1)

7 (7.7)

=0.7

Colon

2 (9.1)

7 (7.7)

=0.7

Mesentery

2 (9.1)

6 (6.6)

=0.6

Retroperitoneal

11 (50)

15 (16.5)

<0.001

Diaphragm

2 (9.1)

8 (13.2)

=0.3

Adrenal

Extra-abdominal

Mean arterial pressure (mmHg), mean±range

2 (9.1)

8 (8.8)

=0.9

15 (68.1)

45 (49.4)

=0.047

67±26.8

84.3±17

=0.02

SD: Standard deviation; HR: Heart rate.

respectively (p=0.047). Mean arterial pressure at admission was found to be significantly lower in patients with mortality when compared to patients without mortality (67±26.8 mmHg versus 84.3±17 mmHg; p=0.02). The number of packed erythrocytes transfused in patients with mortality was 8.8±8.6 units, whereas it was 3.3±5.9 units in the patients without mortality. This difference between the patients with and without mortality was statistically significant (p=0.047). Other clinical and trauma-related characteristics did not significantly differ among patients with and without mortality. The laboratory values in patients with and without mortality were also analyzed (Table 2). Mean platelet count in patients with and without mortality was 70887±100294 corpuscles/mL and 108134±120002 corpuscles/mL, respectively (p=0.057). Although this difference did not reach statistical significance, the p-value is very close to 0.05 and maybe more significant with a higher volume of patients in the future. Mean international normalized ratio (INR) was significantly higher in patients with mortality when compared to patients without mortality (4.3±7.1 versus 2.7±4; p=0.016). Mean lactate dehydrogenase (LDH) level in patients with mortality was 46

1685.7±333.8 IU/mL, whereas it was 675.8±565.3 IU/mL in patients without mortality. This difference was statistically significant (p<0.001). Mean aspartate aminotransferase (AST) level in patients with and without mortality was 850±2349.6 IU/mL and 239±366.05 IU/mL, respectively (p<0.001). Mean alanine aminotransferase (ALT) was significantly higher in patients with mortality when compared to patients without mortality (430±619 versus 244±448 IU7mL; p<0.001). Mean alkaline phosphatase (ALP) level in patients with mortality was 76.9±72.8 IU/mL, whereas it was 67.3±27.8 IU/mL in patients without mortality. This difference was statistically significant (p=0.003). Other laboratory values did not show significant differences among patients with and without mortality.

Risk Factors Determining Mortality We determined the cut-off values for INR, LDH, ALT, ALP and mean arterial pressure on admission with ROC analysis. These cut-off values were included in the logistic regression analysis to analyze the risk factors determining mortality in the patients. Multivariate analysis showed that retroperitoneal injury (HR: 5.7 CI: 95% Range: 1.9–16.3; p=0.001) and Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Gönültaş et al. Analysis of risk factors of mortality in abdominal trauma

Table 4. Distribution of the parameters among the study groups

Exitus Alive p

Mean±SD Mean±SD

Transfusion

8.8±8.6

3.3±5.9 =0.047

Hemoglobin (g/dL)

10.4±4.8

10.4±4.3

=0.9

Hematocrit (%)

26.4±11.8

31.6±12.3

=0.8

Platelet (corpuscle/mm ) 3

70887±106294 108134±120002 =0.057

Neutrophil (corpuscle/mm3) Leukocyte (corpuscle/mm ) 3

International normalized ratio

67±22.4

70.1±23.3 =0.9

12100±8187 15516±8387 =0.9 4.3±7.1

2.7±4

164.2±135.7

790±249.6

=0.1

1.2±0.7

0.7±0.4

=0.057

1685.7±333.8

675.8±565.3

<0.001

850±2349.6

239±366.5

<0.001

Alanine aminotransferase (IU/mL)

430±619

244±448

=0.048

Total bilirubin (mg/dL)

0.3±0.5

0.3±0.4

=0.2

Fibrinogen (Units/mL) Creatinine (mg/dL) Lactate dehydrogenase (IU/mL) Aspartate aminotransferase (IU/mL)

Direct bilirubin (mg/dL)

=0.016

0.1±0.2

=0.2

Alkaline phosphatase (IU/mL)

76.9±72.8

67.3±27.8

=0.003

Gamma glutamyl transferase (IU/mL)

28.7±27.2

31.7±26.1

=0.7

2.4±0.9

2.8±1.1

=0.4

166±59.5

166±57

=0.7

Albumin (g/dL) Glucose (mg/dL) SD: Standard deviation.

ALT >519 IU/mL (HR: 4.5 CI: 95% Range: 1.3–15; p=0.015) levels before the operation were independent risk factors predicting mortality.

DISCUSSION Abdominal trauma is a major world health problem leading to mortality in more than 30% of the cases.[3] In the present study, we found that there is no gender difference concerning the trauma type, most frequent mechanism of injury was blunt abdominal trauma which is mostly due to vehicle collisions and liver was affected in 87% of the patients and 80% of the patients required surgery for their injuries. Furthermore, we found that the presence of retroperitoneal injury predicted the mortality of the patients (68.1% versus 49.4%). The blunt abdominal trauma rate was observed in 86.4% of the emergency department admissions in the present study. Blunt abdominal trauma, frequently injured extra-abdominal regions are a thoracic cavity in 45% of the cases and central nervous system in 42% of the patients.[11] In the present study, we also found thorax to be the most frequent site of extraabdominal injury, which is observed in 23.9% of the cases. Central nervous system injury was observed in 13.3% of the cases, which was the second most frequent site of extra-abdominal injury. Furthermore; the presence of extra-abdominal injury was significantly higher in patients with mortality. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

In the present study, 79.4% of the patients were male. In the literature, male are more frequent victims of both blunt and penetrating abdominal trauma, and reported rates have been 82–88%.[5,12–14] This difference is because males are more active in daily life and subject to road traffic accidents and interpersonal conflicts. Furthermore, we found no difference about gender distribution in patients with and without mortality. This suggests that although females are infrequent victims of abdominal, trauma-related mortality developed more frequently in female patients. It has been reported that females are vulnerable to brain injury due to various reasons. [15] This may explain the difference between trauma frequency and mortality rates between the two genders. The mortality rate of abdominal trauma has been reported to range between 2 to 27% in cases with early admissions, whereas in late admissions, mortality is reported to increase to 4 to 36%.[4,10,11] In the present study, the mortality rate was 19.4%. The majority of causes of death are due to occult central nervous system injuries and irreversible hemorrhagic shock. Our result suggests that admissions to the emergency department were relatively late, and the patient’s general condition is more critical. The difference of distribution of age between the patients with and without mortality (37.9 versus 35.6 years) is not a major difference and these patients can be considered as being at the same age interval. Therefore, we can easily say that age is not a determining factor for the development of mortality in patients with abdominal trauma. 47

Gönültaş et al. Analysis of risk factors of mortality in abdominal trauma

The retroperitoneal injury was an independent risk factor for mortality in the present study. Haddad et al.[16] have also reported retroperitoneal hematoma to be an independent risk factor of mortality. We believe this can be explained by the energy of trauma and any trauma leading to retroperitoneal injury is the result of a high-energy injury and therefore, the mortality of the patients might have increased. Various trauma scores, including Injury Severity Score (ISS) and Revised Trauma Scores (RTS), have been used to describe the severity of the injury. Karaca et al.[17] found that ISS >50 was a predictor of mortality in gunshot wound injuries. Both Haddad et al.[16] (ISS=37 versus 29) and Gad et al.[12] (Low RTS was associated with five times higher mortality rate) have reported more severe trauma in patients with mortality, all of which supports our hypothesis.

Consumption coagulopathy and platelet dysfunction are prominent features of severe hemorrhagic shock.[20] In the present study, we found lower mean platelet counts and increased INR in abdominal trauma patients with mortality when compared to patients without mortality. This is a reflection of the degree of blood loss that resulted in platelet dysfunction and coagulopathy due to consumption. However, the results of the present study should be evaluated with caution. The limitations of the present study are its retrospective design and lack of trauma severity score data. Furthermore, we are a tertiary referral center; therefore, more critical patients admitted to our emergency department, which may cause higher mortality rates in our patients. However, this is a high volume study from a single institution, and the results contribute to the general literature.

Experimental models of ischemia and reperfusion injury have shown that ALT, AST, LDH are markers showing the extent of liver injury.[18] Therefore, if these laboratory parameters are high, the extent of liver injury is high. In the present study, we found higher ALT, AST and LDH levels in patients with mortality. This is related to the trauma severity and the extent of liver injury. Furthermore, ALT levels over 519 IU/mL were an independent risk factor for mortality, which is the unique finding of the present study. Hemodynamic parameters of the patients have been shown to increase the mortality risk of the patients.[2,3,19]

In conclusion, the results of the present study suggest that upon admission patients with anemia, low mean arterial pressure elevated AST, ALT, ALP, LDH, thrombocytopenia and retroperitoneal injury have a higher risk of mortality. Among these parameters, ALT over 519 IU/mL and the presence of retroperitoneal injury were independent risk factors for mortality in patients with abdominal trauma. The results of the present study can be confirmed with multi-institutional studies and a trauma score can be developed for the patients.

Systolic blood pressure has been frequently reported parameter, and blood pressures below 60–90 mmHg have been shown to increase mortality nearly four times,[2,3] We evaluated the differences in mean arterial pressures between patients with and without mortality. We found that patients with mortality had significantly lower mean arterial pressure when compared to patients without mortality. This result suggests the severity of hemorrhagic shock upon admission to the emergency department. However, our logistic regression analysis did not show mean arterial pressure as an independent risk factor for mortality. Low hemoglobin levels have previously been reported to be lower in fatal abdominal trauma.[2,12] Furthermore, patients with anemia were reported to have five times higher mortality risk.[2] In the present study, hemoglobin levels of the patients with mortality were lower than the patients without mortality. Hemoglobin is an indirect determinant of the amount of blood loss of the patients. Therefore, lower hemoglobin levels suggest more severe hemorrhagic shock in the patients. Although we did not find a significant difference in the hemoglobin levels between the patients with and without mortality, we found higher transfusion rates in patients with mortality mean 8.8 units of ES versus 3.3 units of ES). Similarly, Baygeldi et al.[19] have found four times more erythrocyte transfusion in patents with morbidity following management of solid organ injuries following blunt and penetrating abdominal trauma. 48

Ethics Committee Approval: Retrospective study. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: F.G.; Design: F.G., K.K.; Supervision: A.F.K.G.; Materials: K.K.; Data: K.K.; Analysis: K.K., T.T.Ş.; Literature search: B.B.; Writing: T.T.Ş.; Critical revision: S.Y. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Treatment Surgery. Doherty GM, Editor. New York, NY: The McGrawHill Companies, 2010. 2. Ntundu SH, Herman AM, Kishe A, Babu H, Jahanpour OF, Msuya D, et al. Patterns and outcomes of patients with abdominal trauma on operative management from northern Tanzania: a prospective single centre observational study. BMC Surg 2019;19:69. 3. Pimentel SK, Sawczyn GV, Mazepa MM, da Rosa FG, Nars A, Collaço IA, et al. Risk factors for mortality in blunt abdominal trauma with surgical approach. [Article in English, Portuguese] Rev Col Bras Cir 2015;42:259−64. 4. Aldemir M, Taçyildiz I, Girgin S. Predicting factors for mortality in the penetrating abdominal trauma. Acta Chir Belg 2004;104:429−34. 5. da Costa LGV, Carmona MJC, Malbouisson LM, Rizoli S, Rocha-Filho JA, Cardoso RG, et al. Independent early predictors of mortality in polytrauma patients: a prospective, observational, longitudinal study. Clinics (Sao Paulo) 2017;72:461−8. 6. Tekesir K, Basak F, Sisik A, Caliskan YK. Epidemiology of trauma with analysis of 138,352 patients: Trends of a single center, Haydarpasa Nu-

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following blunt abdominal trauma. Clin Ter 2014;165:23−6.

7. Ülkü A. Prognostic factors in blunt abdominal trauma patients undergoing laparotomy and prognostic value of trauma scoring systems. Cukurova Med J 2018;43:994−1001.

14. Malinoski DJ, Patel MS, Yakar DO, Green D, Qureshi F, Inaba K, et al. A diagnostic delay of 5 hours increases the risk of death after blunt hollow viscus injury. J Trauma 2010;69:84−7.

8. Özpek A, Yücel M, Atak İ, Baş G, Alimoğlu O. Multivariate analysis of patients with blunt trauma and possible factors affecting mortality. Ulus Travma Acil Cerrahi Derg 2015;21:6:477−483.

15. Vagnerova K, Koerner IP, Hurn PD. Gender and the injured brain. Anesth Analg 2008;107:201−14.

9. Malkomes P, Störmann P, El Youzouri H, Wutzler S, Marzi I, Vogl T, et al. Characteristics and management of penetrating abdominal injuries in a German level I trauma center. Eur J Trauma Emerg Surg 2019;45:315−21. 10. Iflazoglu N, Ureyen O, Oner OZ, Tusat M, Akcal MA, et al. Complications and risk factors for mortality in penetrating abdominal firearm injuries: analysis of 120 cases. Int J Clin Exp Med 2015;8:6154−62. 11. Harmston C, Ward JBM, Patel A. Clinical outcomes and effect of delayed intervention in patients with hollow viscus injury due to blunt abdominal trauma: a systematic review. Eur J Trauma Emerg Surg 2018;44:369−76. 12. Gad MA, Saber A, Farrag S, Shams ME, Ellabban GM. Incidence, patterns, and factors predicting mortality of abdominal injuries in trauma patients. N Am J Med Sci 2012;4:129−34. 13. Arikanoglu Z, Turkoglu A, Taskesen F, Ulger BV, Uslukaya O, Basol O, et al. Factors affecting morbidity and mortality in hollow visceral injuries

16. Haddad SH, Yousef ZM, Al-Azzam SS, AlDawood AS, Al-Zahrani AA, AlZamel HA, et al. Profile, outcome and predictors of mortality of abdomino-pelvic trauma patients in a tertiary intensive care unit in Saudi Arabia. Injury 2015;46:94−9. 17. Karaca MA, Kartal ND, Erbil B, Öztürk E, Kunt MM, Şahin TT, et al. Evaluation of gunshot wounds in the emergency department. Ulus Travma Acil Cerrahi Derg 2015;21:248−55. 18. Datta G, Fuller BJ, Davidson BR. Molecular mechanisms of liver ischemia reperfusion injury: insights from transgenic knockout models. World J Gastroenterol 2013;19:1683−98. 19. Baygeldi S, Karakose O, Özcelik KC, Pülat H, Damar S, Eken H, et al. Factors Affecting Morbidity in Solid Organ Injuries. Dis Markers 2016;2016:6954758. 20. Peralta R, Vijay A, El-Menyar A, Consunji R, Afifi I, Mahmood I, et al. Early high ratio platelet transfusion in trauma resuscitation and its outcomes. Int J Crit Illn Inj Sci 2016;6:188−93.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Abdominal travmada mortaliteyi etkileyen risk faktörlerinin analizi Dr. Fatih Gönültaş,1 Dr. Koray Kutlutürk,1 Dr. Ali Fuat Kaan Gök,2 Dr. Bora Barut,1 Dr. Tevfik Tolga Şahin,1 Dr. Sezai Yılmaz 1 2

İnönü Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Malatya İstanbul Üniversitesi İstanbul Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul

AMAÇ: Bu çalışmanın amacı, acil servisimizde değerlendirilen künt ve penetran karın travmaları ve bunlara yönelik gerçekleştirilen tedavi yaklaşımları ile mortalite için risk faktörlerini incelemektir. GEREÇ VE YÖNTEM: Ocak 2009–Nisan 2019 tarihleri arasında acil servisimize başvuran ve travma nedeniyle cerrahi konsültasyonu yapılan 664 hasta çalışma için değerlendirildi. Başvuru anında gerçekleşen ölümler, verileri eksik olan hastalar ve karın travması saptanmayan hastalar çalışmaya dahil edilmedi. Çalışmaya abdominal travmalı 113 hasta alındı. Demografik, klinik, prognostik ve mortalite ile ilişkili faktörler geriye dönük olarak incelendi. BULGULAR: Hastalardaki yaş ortalaması 36.08±16.1 yıldı. Bunlardan 90’ı erkekti. Seksen hastada (%70.8) künt karın travmasının (KKT) mevcut olduğu gözlendi. Yimi sekiz hastada (%24.7) izole karaciğer ve iki hastada (%1.7) dalak yaralanması vardı. Kombine karaciğer ve dalak yaralanmasının iki hastada (%1.7) görüldü. Yirmi iki (%19.4) hastada mortalite gelişti. Mortalite nedenlerini geri dönüşümsüz hemorajik şok (%40.9) ve merkezi sinir sistemi (%13.6) yaralanmaları oluşturmaktaydı. KKT mortal seyreden grupta ana yaralanma mekanizmasını oluşturmaktaydı (%86.4 ve %67, p<0.001). Retroperitoneal yaralanma sıklığı mortal seyreden hastalarda anlamlı olarak daha yüksekti (%50 ve %50, %16, p<0.001). Mortal seyreden hastalarda ekstra abdominal yaralanma sıklığı daha yüksekti (%49 ve %68.1; p=0.047). Yatış sırasındaki ortalama arter basıncı mortal seyreden hastalarında anlamlı olarak düşük bulundu (67±26.8 mmHg ve 84.3±17 mmHg; p=0.02). Mortal seyreden hastalarda transfüze edilen eritrosit miktarı daha fazlaydı (8.8±8.6 ve 3.3±5.9 ünite; p=0.047). Ortalama uluslararası normalleştirilmiş oranı (INR) mortal seyreden hastalarda anlamlı derecede yüksekti (4.3±7.1 ve 2.7±4; p=0.016). Mortal seyreden hastalarda ortalama laktat dehidrogenaz daha yüksekti (1685.7±333.82 ve 675.8±565.3 IU/mL; p<0.001). Ortalama alanin amino transferaz (ALT) düzeyi mortal seyreden hastalarda anlamlı olarak daha yüksekti (430±619 ve 244±448 IU/mL; p<0.001). Mortal seyreden hastalarda ortalama alkalen fosfataz (ALP) düzeyi daha yüksekti (76.9±72.8 ve 67.3±27.8 IU/mL; p=0.003). Retroperitoneal yaralanma ve ALT >519 IU/mL varlığının mortalite açısından bağımsız risk faktörleri oldukları bulundu. TARTIŞMA: Mortal seyreden hasta grubunda bazı laboratuvar değişkenlerinin arttığını ve bunların travmanın ciddiyeti ile ilgili olduğu görüldü. Retroperitoneal yaralanma ve artmış ALT düzeyleri mortalite açısından bağımsız risk faktörü olup, bu bulgu çalışmanın en önemli bulgusu olarak karşımıza çıkmaktadır. Mevcut çalışma bulgularımız travma hastalarının değerlendirilmesinde diğer merkezlere rehberlik edebileceği ve yüksek riskli grupları tanımlamada da kullanılabilir. Anahtar sözcükler: Abdominal travma; künt karın tarvmaları; mortalite; penetran karın yaralanmaları. Ulus Travma Acil Cerrahi Derg 2020;26(1):43-49

doi: 10.14744/tjtes.2019.12147

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ORIGIN A L A R T IC L E

Spontaneous abdomen and abdominal wall hematomas due to anticoagulant/antiplatelet use: Surgeons’ perspective in a single center Muhammet Kadri Çolakoğlu, M.D., Ali Özdemir, M.D., Süleyman Kalcan, M.D., Ali Demir, M.D., Gökhan Demiral, M.D., Ahmet Pergel, M.D. Department of General Surgery, Recep Tayyip Erdoğan University Training and Research Hospital, Rize-Turkey

ABSTRACT BACKGROUND: The incidence of abdominal wall hematomas increased after the introduction of anticoagulant and antiplatelet drugs in clinical practice. These patients are usually old, and they have more than one comorbidity. Most spontaneous hematomas tend to limit itself and conservative treatment with close follow up is usually enough, but surgery is an option that should be decided critically. Unnecessary surgical interventions could worsen the situation. The present study aims to analyze the results of patients under anticoagulant/antiplatelet treatment and with spontaneous abdominal wall hematomas from surgeons’ perspective. METHODS: This is a retrospective study that the medical records of 43 patients who were under anticoagulant/antiplatelet therapy and consulted our general surgery clinic because of the spontaneous abdomen and abdominal wall hematoma between January-2016 and September-2018 were reviewed. RESULTS: The findings showed that most of the cases were presented with abdominal pain. Thirty of these patients were female (69.7%). The mean age was 69.32 years. More than half of the patients (58.1%) were referred from the emergency department. All of the cases were under anticoagulant and antiplatelet treatment for several reasons. With presenting signs and symptoms and after evaluation of laboratory tests, computed tomography was performed to 30 patients (69.7%) as an initial test. USG and MRI were the other methods used. The most common diagnosis was rectus sheath hematoma (n=16; 37.2%) and followed by intestinal and colon wall, lumbar, psoas, pelvic and retroperitoneal hematoma in decreasing order. Among 43 patients, 39 patients (90.6%) followed with conservative treatment and two patients were treated with transcatheter arterial embolization. Two patients (4.6%) were died on day 1 and 11 after diagnosis. No surgery needed for all patients. CONCLUSION: Early recognition, hospitalization of risky patients, close follow-up of hemodynamic parameters, patients’ response to conservative treatment and minimal invasive methods are key points. Conservative care is the choice of treatment, but surgery must always keep in mind in hemodynamic unstable patients. Keywords: Abdominal wall; anticoagulant; antiplatelet; hematoma.

INTRODUCTION Abdominal wall hematomas, such as rectus sheath and psoas are clinical conditions that may occur after trauma, surgery, interventional procedures, or may spontaneously happen, especially in older patients who are receiving anticoagulant/antiplatelet therapy. Spontaneous abdominal wall hematomas are strongly related to anticoagulant/antiplatelet use and there is a

well-described increase in incidence, especially in rectus sheath hematomas, after the introduction of anticoagulant/antiplatelet therapy in the field.[1–3] These patients with spontaneous abdominal wall hematomas usually present in emergency services with complaints as a mass in the abdomen, acute abdominal pain, dizziness, vomiting, and ileus or may present in shock as in progressive occasions. In clinical practice, at a considerable rate, patients in different departments treated for different

Cite this article as: Çolakoğlu MK, Özdemir A, Kalcan S, Demir A, Demiral G, Pergel A. Spontaneous abdomen and abdominal wall hematomas due to anticoagulant/antiplatelet use: Surgeons’ perspective in a single center. Ulus Travma Acil Cerrahi Derg 2020;26:50-54. Address for correspondence: Muhammet Kadri Çolakoğlu, M.D. Recep Tayyip Erdoğan Üniversitesi Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, Rize, Turkey Tel: +90 464 - 213 04 91 E-mail: drkadri@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):50-54 DOI: 10.14744/tjtes.2019.32485 Submitted: 30.10.2018 Accepted: 25.02.2019 Online: 30.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Çolakoğlu et al. Spontaneous abdomen and abdominal wall Hematomas due to anticoagulant/antiplatelet use

reasons can be determined incidentally with varied imaging methods. Especially these patients from cardiology, pulmonary medicine, or other surgical unites may bring about a dilemma for general surgeons. Treatment options include conservative, interventional and surgical methods. A general surgeon must be aware of which method could be suitable for the patient because these patients are old, have a wide range of morbidities, already have bleeding diathesis and surgery could be fatal for most of them. Most of the hematomas limit themselves and conservative management may be sufficient, but as in the group of patients mentioned above could be mortal at a rate of 4–20%.[4] Hemodynamic instability to multiple organ failure or death is a frightening situation.[5] Making a surgical decision could be very difficult and unnecessary surgical interventions may worsen the clinical situation. In this study, patients who were consulted to a general surgery department and who were under anticoagulant/antiplatelet treatment and had an abdominal wall hematoma were evaluated retrospectively. We aimed to report a series of 43 patients with their characteristics, clinical conditions and treatment results and try to answer the surgeon’s dilemma with our single-center perspective.

MATERIALS AND METHODS The medical records of patients who were under anticoagulant/antiplatelet therapy and consulted to our general surgery clinic because of the abdomen and abdominal wall hematoma between January-2016 and September-2018 were reviewed retrospectively. Patients were mostly consulted from the emergency department and other units, such as intensive care, cardiology or pulmonary medicine. Patients who had abdominal wall hematoma but not a history of anticoagulant/antiplatelet usage or patients with hematological or coagulation disorders or had major trauma or surgery recently were excluded. The records of 43 patients who met the conditions were examined. The demographic data, comorbidities of patients, history of anticoagulant/antiplatelet drug usage, presenting signs and symptoms, use of imaging methods, clinical follow-up, and use of blood supplies, treatment methods and end-results were evaluated. International normalized ratio (INR) results and length of hospital stay were also documented and we also tried to identify predisposing factors for spontaneous abdominal wall hematoma. This study was conducted in a university hospital, and all data were collected and evaluated after the study was approved by the same institute’s ethics committee (date: 09.03.2018, no: 2018/50).

Statistical Analysis Statistical Package for the Social Sciences (SPSS 21 Inc., Chicago, IL, USA) was used for statistical analysis. The collected data were expressed as means (±SD), minimums and maximums, or percentage. HTC and INR levels at the time of diagnosis and at the time of discharge were compared using a paired t-test. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

RESULTS Between January-2016 and September-2018, 43 patients who had abdominal wall hematoma and had a history of anticoagulant/antiplatelet usage were consulted to our general surgery department. Thirty of these patients were female (69.7%). The mean age was 69.32 years (70.43 years for female and 66.76 years for male). All patients were consulted from other departments. The highest number was from emergency department (58.1% 25 patients) and followed by cardiology (n=5), pulmonary medicine (n=5), intensive care unit (n=3), internal medicine (n=2), urology (n=2) and gynecology (n=1) in decreasing order. The demographic and clinical characteristics of patients are summarized in Table 1 and the indications, and numbers of anticoagulant/antiplatelet usage of these patients are summarized in Table 2. All patients were either hospitalized patients (n=18) that were treated in different departments for different reasons or patients who presented to the emergency department for various reasons (n=25). No matter where the patient was referred to the general surgery department, the most frequent reason for consultation was a pain (n=37, 86%). The pain was mostly located on the anterior abdominal wall, but groin and lumbar regions were also located. Nausea, abdominal mass, melena, hematuria, or sub-ileus symptoms were also seen in addition to pain. With these presenting signs and symptoms and after evaluation of laboratory tests, computed tomography (CT) was performed to 30 patients (69.7%) as an initial test. Ultrasound (USG) was the first imaging modality of choice in seven patients. One patient had both USG and CT and magnetic resonance imaging (MRI) needed for two patients after USG evaluation. No imaging methods required for three patients. The most common diagnosis after evaluation of these imaging methods was rectus sheath hematoma (n=16; 37.2%). Intestinal and colon wall, lumbar, psoas, pelvic and retroperitoneal hematoma followed this in decreasing ratio. Patients presenting signs and symptoms, imaging tests and location of hematomas are all summarized in Table 3. Eighteen patients were already hospitalized in different departments. Among 25 patients that were consulted from the emergency department, 21 of them (84%) hospitalized and followed in the general surgery department, and four of them followed in the outpatient clinic. At the time of hematoma detection, initial hemogram and INR values of all patients were evaluated. The mean hemoglobin value at the time of diagnosis was 10.4±2.5g/dL (4.8–16). Nineteen patients (44.1%) had a hemoglobin value under 10g/dL. Twenty patients (46.5%) needed at least one erythrocyte suspension during their hospitalization period. The mean number of erythrocyte suspension used was 3.5±1.7 (1–7). The mean INR value at the time of diagnosis was 3.2±2.3. Eighteen patients (41.8%) had an INR value over 3. Twenty-four patients needed (55.8%) at least one fresh frozen plasma transfusion for supportive care. The mean number of plasma transfusion 51

Çolakoğlu et al. Spontaneous abdomen and abdominal wall Hematomas due to anticoagulant/antiplatelet use

Table 1. Demographic and clinical characteristics of the patients

Table 3. Sign and symptoms, imaging methods used, location of the hematoma

Gender (n=43)

Female

30 (69.7%)

Male

13 (30.2%)

Age (years)

69.32 (22–89)

Female

70.43

Male

66.76

Comorbidities

Heart failure

Hypertension

Diabetes mellitus

Arrhythmia

Coronary artery disease

Pulmonary embolism

Chronic obstructive pulmonary disease

Cerebrovascular disease

Chronic renal failure

Other

Presenting sign and symptoms

Abdominal pain

Abdominal mass with pain

Groin pain

Symptoms of ileus

Lumbar pain

Pain with nausea

Melena

Hematuria

General condition disorder

Imaging methods used

Computed tomography

Ultrasound

30 7

Magnetic resonance imaging

Ultrasound with computed tomography

No imaging methods

Location of hematoma

Table 2. Indications and numbers of anticoagulant/antiplatelet usage

Anticoagulant treatment (n=27, 62.7%)

Oral anticoagulant

Low-molecular-weight heparin

Rectus sheath hematoma

Intestinal and colon wall

Lumbar

Rectus sheath with retroperitoneum

Psoas muscle

Pelvic

Retroperitoneum

Antiplatelet treatment (n=13, 30.2%)

Acetylsalicylic acid

Klopidogrel

Both

Anticoagulant + Antiplatelet treatment (n=3, 6.9%)

Indications

Atrial fibrillation

Coronary artery disease

Valve replacement

Valve disease

Cerebrovascular disease

Pulmonary embolism

used was 3±1.8 (1–8). Platelet counts were between normal ranges for all patients. Among 43 patients, 39 patients (90.6%) followed with conservative treatment (follow-up for outpatient clinic patients, blood and plasma transfusion, and Vitamin K and IV supportive care if needed). Additional USG or CT screenings performed 52

according to the patient’s clinical course. Five patients (11.6%) followed in the intensive care unit (ICU). Three patients were consulted from the ICU unit, and two patients were transferred from the general surgery department. Two patients were treated with transcatheter arterial embolization, and hematoma of them was drained with the help of interventional radiology because of obstruction symptoms in intestinal and urinary passages. Two patients (4.6%) died on day 1 and 11. Both were followed for different comorbidities and consulted from ICU unite after the detection of the hematoma. One patient had retroperitoneal and one patient had pelvic wall hematoma, but surgery was not indicated according to their symptoms, laboratory results and radiological findings. The mean length of hospital stay was 7.8±5 days (1–20). All patients were followed up very closely and followed with a conservative approach and radiology support when necessary. No surgery needed for all patients.

DISCUSSION After the introduction of anticoagulant and antiplatelet use Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Çolakoğlu et al. Spontaneous abdomen and abdominal wall Hematomas due to anticoagulant/antiplatelet use

in clinical practice, the incidence of spontaneous abdominal and abdominal wall hematomas increased, especially in patients with older ages.[6] These patients usually referred to the emergency department because of abdominal pain even hematomas are the uncommon cause of acute abdominal pain.[7–9] Pain in the groin or lumbar region, abdominal masses, symptoms of intestinal obstruction, or hypovolemic shock in advanced situations also can be seen[10] as in our series. Treatment choices could be a contradiction for surgeons. Older ages, comorbidities and susceptibility of patients to bleeding can lead surgeons into two different ways. The first way is avoiding surgery, but being too late could start the cascade from organ failure to death. The second way is an early decision of surgery, but unnecessary operations could worsen the situation that could already limit itself. To overcome this dilemma, we strongly believe that early recognition, hospitalization of risky patients, close follow-up of hemodynamic parameters, patient’s response to conservative treatment and minimal invasive methods are key points. Surgery should always keep in mind, and decisions should be made after evaluation of these vital points. As an endpoint, literature mentions that surgery should be performed only cases that hemodynamic stability cannot be established.[7,11–13] For a close follow-up, imaging methods are important and can be repeated if necessary. USG can be used as an initial test and for non-complicated hematomas, but CT and even MRI can be performed if necessary. In our study, 69.7% of the patients had CT as an initial test because of two reasons. First, abdominal hematomas were also included in this study, and we believe that CT is more accurate and necessary for detecting the size and location of intraabdominal hematomas in this risky group of patients. Second, most of the patients referred from the emergency department, and CT is the preferred imaging method in clinical practice. MRI could be performed in patients whose renal functions were not suitable for injection of contrast agent as we did in our series.[14,15] The rapid increasing size of the hematoma and alternating hemodynamic functions should alert surgeons for surgery. Most patients can be followed with a conservative treatment until hematoma size, and hemogram results remain stable.[10] Interventional radiology methods are less invasive and effectively used in high-risk patients.[16] In our series, we also used transcatheter arterial embolization for two cases that did not respond to conservative treatment and had a high-risk for surgery. Both cases were successfully treated. The mortality rate was 4.6% in our series. Mortality rates vary from study to study and in a range of 2–20% in the relevant literature. Two patients who had retroperitoneal and pelvic wall hematoma and followed in the ICU unit died on day 1 and 11. Both patients had multiple comorbidities, and surgery was not indicated according to their symptoms, laboratory results and radiological findings at the time of first evaluation. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

When considering this information from the perspective of a surgeon, a simple question arises: So what is the place of a surgeon in the treatment of abdominal wall hematoma? As seen in the literature and supported by our series, the conservative approach is sufficient in most patients. However, the surgical decision is found to be beyond a critical and thin line, especially in patients with high morbidity and in cases who are hemodynamically unstable. Thus, we suggest that diagnostic workup and treatment management should be performed with a multidisciplinary approach led by the surgeon. Regardless of who evaluated the patient first, a surgical opinion should be taken and treatment decisions should be given together. Hence, the patient’s hemodynamic status, comorbidities and age are very important and risky patients should be followed up in the intensive care unit. We recommend performing CT imaging in patients with major complaints (such as ileus and hematuria), except for hemodynamic status or pain, although USG imaging is sufficient in mild cases and minor hematomas. Abdominal organ wall hemorrhages can be easily distinguished by CT and, if necessary, the progression of hemorrhage can be monitored by sequential imaging. For patients who do not respond to conservative treatment, we recommend minimally invasive methods (interventional radiology) if the patient’s condition is appropriate, especially in patients with a high risk of morbidity and mortality for surgery. Patients who need a continuous blood transfusion, hemodynamically unstable and progression of hematoma with other pathologies that require surgery should be taken to the operation room without delay. Since this process can develop in minutes, the surgeon’s opinion should be taken in the management of all patients. There are some limitations to this study. First of all, it is a retrospective study and patients were evaluated according to their patient charts and medical records. Secondly, there is no data about short term and long term follow up results after discharge. All patients continued their medical treatments according to their indications. Third, hospitalization was not directly indicated only for a hematoma in all patients. Eighteen patients were already hospitalized in different departments for different reasons, and hematoma detected at the time of their hospitalization.

Conclusion Abdominal and abdominal wall hematomas are strongly associated with anticoagulant/antiplatelet use. The metabolic effects of these drugs should be closely monitored in this group of patients. Pain in elderly patients using these drugs should be a warning about hematoma. Early recognition, hospitalization of risky patients, close follow-up of hemodynamic parameters, patients’ response to conservative treatment and minimal invasive methods are key points. Conservative care is the choice of treatment, but surgery must always keep in mind in hemodynamic unstable patients. 53

Çolakoğlu et al. Spontaneous abdomen and abdominal wall Hematomas due to anticoagulant/antiplatelet use

Ethics Committee Approval: Approved by the local ethics committee (date: 09.03.2018, no: 2018/50). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: M.K.Ç., A.Ö.; Design: M.K.Ç., A.Ö.; Supervision: A.P., G.D.; Materials: A.Ö., S.K.; Data: M.K.Ç., A.Ö., A.D.; Analysis: M.K.Ç., A.D.; Literature search: M.K.Ç., S.K., A.Ö.; Writing: M.K.Ç.; Critical revision: A.P., G.D. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Scott WW Jr., Fishman EK, Siegelman SS. Anticoagulants and abdominal pain. The role of computed tomography. JAMA 1984;252:2053−6. 2. Fitzgerald JE, Fitzgerald LA, Anderson FE, Acheson AG. The changing nature of rectus sheath haematoma: case series and literature review. Int J Surg 2009;7:150−4. 3. Alla VM, Karnam SM, Kaushik M, Porter J. Spontaneous rectus sheath hematoma. West J Emerg Med 2010;11:76−9. 4. Donaldson J, Knowles CH, Clark SK, Renfrew I, Lobo MD. Rectus sheath haematoma associated with low molecular weight heparin: a case series. Ann R Coll Surg Engl 2007;89:309−12. 5. Cherry WB, Mueller PS. Rectus sheath hematoma: review of 126 cases at a single instution. Medicine (Baltimore) 2006;85:105−10. 6. Risch O, Alfidja A, Mulliez A, Amani AH, Boyer L, Camilleri L, et al. Severe non-traumatic bleeding events detected by computed tomography: do anticoagulants and antiplatelet agents have a role? J Cardiothorac Surg

2014;9:166. 7. Aktürk OM, Kayılıoğlu SI, Aydoğan I, Dinc T, Yıldız B, Cete M, et al. Spontaneous rectus sheath hematoma: an overview of 4-year single center experience. Indian J Surg 2015;77:1219−21. 8. Siu WT, Tang CN, Law BK, Chau CH, Li MK. Spontaneous rectus sheath hematoma. Can J Surg 2003;46:390 9. Maharaj D, Ramdass M, Teelucksingh S, Perry A, Naraynsingh V. Rectus sheath haematoma: a new set of diagnostic features. Postgrad Med J 2002;78:755−6. 10. Pei MW, Hu MR, Chen WB, Qin C. Surgical Treatment of a Giant Spontaneous Abdominal Wall Hematoma. Chin Med J 2017; 130:1621−2. 11. Carkman S, Ozben V, Zengin K, Somuncu E, Karatas A. Spontaneous rectus sheath hematoma: an analysis of 15 cases. Ulus Travma Acil Cerrahi Derg 2010;16:532−6. 12. Dag A, Ozcan T, Turkmenoglu O, Colak T, Karaca K, Canbaz H, et al. Spontaneous rectus sheath hematoma in patients on anticoagulation therapy. Ulus Travma Acil Cerrahi Derg 2011;17:210−4. 13. Gundes E, Cetin DA, Aday U, Ciyiltepe H, Deger KC, Uzun O, et al. Spontaneus rectus sheath hematoma in cardiac patients: a single-center experience Ulus Travma Acil Cerrahi Der 2017;23:483−8. 14. Virmani V, Sethi V, Fasih N, Ryan J, Kielar A. The abdominal wall lumps and bumps: cross-sectional imaging spectrum. Can Assoc Radiol J 2014;65:9−18. 15. Leonardou P, Kierans AS, Elazazzi M, Shaikh F, Semelka RC. MR imaging findings of small bowel hemorrhage: two cases of mural involvement an done of perimural J Magn Reson Imaging 2009;29:1185−9. 16. Nakayama T, Ishibashi T, Eguchi D, Yamada K, Tsurumaru D, Sakamoto K, et al. Spontaneous internal oblique hematoma successfully treated by transcatheter arterial embolization. Radiat Med 2008;26:446−9.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Antikoagülan/antiplatelet kullanımına bağlı spontan abdomen ve abdominal duvar hematomları: Tek merkez, cerrah perspektifi Dr. Muhammet Kadri Çolakoğlu, Dr. Ali Özdemir, Dr. Süleyman Kalcan, Dr. Ali Demir, Dr. Gökhan Demiral, Dr. Ahmet Pergel Recep Tayyip Erdoğan Üniversitesi Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, Rize

AMAÇ: Abdominal duvar hematomlarının insidansı, klinik uygulamada antikoagülan ve antiplatelet ilaçların kullanılmasından sonra artmıştır. Bu hastalar genellikle yaşlıdır ve birden fazla komorbiditeye sahiptirler. Çoğu spontan hematom kendini kısıtlama eğilimindedir ve yakın takip ile konservatif tedavi genellikle yeterlidir ancak cerrahi, kritik olarak karar verilmesi gereken bir seçenektir. Gereksiz cerrahi müdahaleler durumu daha da kötüleştirebilir. Bu çalışmanın amacı, antikoagülan/antiplatelet tedavi altındaki ve spontan abdominal duvar hematomları olan hastaların sonuçlarını cerrahi perspektiften incelemektir. GEREÇ VE YÖNTEM: Bu çalışma, Ocak 2016 ve Eylül 2018 yılları arasında antikoagülan/antiplatelet tedavi gören ve spontan abdomen ve abdominal duvar hematomu nedeniyle genel cerrahi kliniğimize başvuran 43 hastanın tıbbi kayıtlarının gözden geçirildiği geriye dönük bir çalışmadır. BULGULAR: Olguların birçoğu karın ağrısı ile başvurdu. Bu hastaların 30’u kadındı (%69.7). Yaş ortalaması 69.32 idi. Hastaların yarısından fazlası (%58.1) acil servisten refere edildi. Olguların tamamı çeşitli nedenlerle antikoagülan ve antiplatelet tedavi altındaydı. Belirti ve semptomların izlenmesi ve laboratuvar testlerinin değerlendirilmesinden sonra 30 hastaya (%69.7) başlangıç testi olarak bilgisayarlı tomografik görüntüleme uygulandı. USG ve MRI kullanılan diğer yöntemlerdi. En sık rastlanan tanı rektus kılıf hematomuydu (n=16; %37.2) ve bunu sırasıyla bağırsak ve kolon duvarı, lombar, psoas, pelvik ve retroperitoneal hematom izledi. Kırk üç hastadan 39’una (%90.6) konservatif tedavi uygulandı ve iki hastaya transkateter arteriyel embolizasyon uygulandı. Tanıdan sonraki birinci ve 11. günde iki hasta (%4.6) hayatını kaybetti. Tedavi için cerrahi uygulama gerekmedi. TARTIŞMA: Erken tanı, riskli hastaların hastaneye yatırılması, hemodinamik parametrelerin yakın takibi, konservatif tedaviye yanıt verme ve minimal invaziv yöntemler tedavide önemli noktalardır. Konservatif bakım ilk tedavi seçeneğidir ancak hemodinamik stabil olmayan hastalarda her zaman cerrahi akılda tutulmalıdır. Anahtar sözcükler: Abdominal duvar; antikoagülan; antiplatelet; hematom. Ulus Travma Acil Cerrahi Derg 2020;26(1):50-54

doi: 10.14744/tjtes.2019.32485

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

ORIGIN A L A R T IC L E

Should we still doubt the success of emergency oncologic colorectal surgery?: A retrospective study Nihan Acar, M.D., Turan Acar, M.D., Erdinc Kamer, M.D., Fevzi Cengiz, M.D., Kemal Atahan, M.D., Haldun Kar, M.D., Mehmet Hacıyanlı, M.D. Department of General Surgery, İzmir Katip Çelebi University Atatürk Training and Research Hospital, İzmir-Turkey

ABSTRACT BACKGROUND: In recent years, the importance of oncologic principles in colorectal cancer (CRC) surgery has been emphasized in many studies. Although emergency surgery is related to high morbidity and mortality rates, their adequacy and prognosis in maintaining oncologic principles are still controversial. This study aims to compare the clinicopathological features of CRC patients who underwent emergency and elective surgical resection and also to evaluate their compatibility with oncologic principles and to evaluate their short/long term results. METHODS: Of the patients who underwent surgery for CRC, 564 were included in this study. The patients were divided into two groups according to their surgical conditions as an emergency (Group 1) and elective (Group 2). Demographics, clinicopathological features, prognostic factors and survival rates of the patients were evaluated retrospectively. RESULTS: There were 104 (18.4%) patients in group 1 and 460 (81.6%) patients in group 2. 61.2% of the patients were male and the mean age was 64.27. There were statistically significant differences between the groups in age distribution, tumor localization, surgical procedures, T- N classification, AJCC stage, presence of mucinous subtype, lymphovascular and perineural invasion. The mean tumor diameter was 5.23±3.48 cm. There was no difference between the groups concerning the adequacy of lymph node harvest, except in patients who underwent low anterior resection. The mean survival time was 475.212 days, and the median survival time was 376 days. The disease-free and overall survival rates were higher in group 2. CONCLUSION: Despite the appropriate oncologic resection, CRC patients operated under emergency conditions had worse short-term and long-term results than the CRC patients operated under elective conditions. Thus, we believe that the prevalence of colorectal cancer screening programs should be increased to reduce the rate of emergency surgery. Keywords: Colorectal cancer; emergency; lymph node; morbidity; mortality; prognosis.

INTRODUCTION Colorectal cancer (CRC) is the third common cancer and the most common malignancy of the gastrointestinal tract. [1] Many countries have been conducting screening programs for the early diagnosis of CRC.[2] These programs also reduce the rate of emergency operation for CRC by detecting the disease without reaching an advanced stage. Many of the patients who undergo emergency surgery present with obstruction, perforation, bleeding and/or peri-

tonitis, which increase the risk of short-term mortality.[3] These acute complications are considered as life-threatening conditions and require swift interventions. The goal of CRC treatment consists of the removal of the primary tumor, together with its lymphovascular structures with clean surgical margins.[4] The total number of removed lymph nodes indicates the oncologic adequacy of the procedure and this number is set at a minimum of 12.[5,6] There are many factors affecting this number, which are related to the patient, physicians (both surgeon and pathologist) and the center.

Cite this article as: Acar N, Acar T, Kamer E, Cengiz F, Atahan K, Kar H, et al. Should we still doubt the success of emergency oncologic colorectal surgery?: a retrospective review. Ulus Travma Acil Cerrahi Derg 2020;26:55-62. Address for correspondence: Nihan Acar, M.D. İzmir Katip Çelebi Üniversitesi Atatürk Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Karabağlar, İzmir, Turkey Tel: +90 232 - 243 43 43 E-mail: cosgunnihan@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):55-62 DOI: 10.14744/tjtes.2019.04043 Submitted: 22.10.2018 Accepted: 01.04.2019 Online: 30.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Acar et al. Emergency oncologic colorectal surgery

The numbers of dissected lymph nodes have increased over the years since the definition of “complete mesocolic/total mesorectal excision” was introduced.[7] Nevertheless, emergency surgical conditions were considered as insufficient to provide these principles.[8] In addition, in the emergency cases, features, such as advanced age, advanced stage, mucinous subtype, lymphovascular and perineural invasion, are encountered at a higher rate.[9,10] Tumor localization also affects the number of lymph node yield and the conditions of emergency surgery. Mortality and morbidity rates are higher in patients who underwent emergency CRC surgery, and the duration of hospitalization is longer in this group.[11] The answers to the questions of whether this substantial amount of patients have different clinicopathological features and whether these patients lack oncologic principles in their treatment when compared to elective cases were sought in various studies.

phovascular- perineural invasion, type of the surgical procedure, ostomy status, condition of the surgery, surgical complications, duration of hospitalization and survival status from 15th of May 2017 were assessed. The primary explanatory variable was tumor location: Right colon cancer (RCC), left colon cancer (LCC), and rectal cancer (RECC). RCCs included tumors in the caecum, ascending colon, hepatic flexure and transverse colon. LCCs included tumors in the splenic flexure, descending colon and sigmoid colon.

Investigations

This study aims to compare the clinicopathological features of CRC patients who underwent elective and emergency surgery, to evaluate their adequacy for oncologic principles, the factors affecting this adequacy and short/long-term outcomes. Our prior hypothesis was that emergency surgery could be adequate as elective surgery, although they have higher rates of mortality and morbidity.

Assessment of the specimens and lymph node count was performed and reported by the Department of Pathology. Metastatic disease was determined with postoperative CT, MRI and/or PET-CT reports in the patients who did not have any evidence of metastasis on preoperative images and surgical exploration. Tumor diameter, total number of dissected lymph nodes, number of metastatic lymph nodes, T stage, N stage, presence of mucinous subtype, lymphovascular and perineural invasion status were obtained from pathology reports and recorded. Information about concomitant complications related to the surgery was obtained from the operative reports, epicrisis reports, postoperative imaging and/ or consultation request reports.

MATERIALS AND METHODS

Surgical Procedures

This study was conducted in accordance with the principles of the Declaration of Helsinki. Ethics committee approval was obtained from our University Medical School Ethics Committee (Number: 31829978-050.01.04-E.1700049773 Date: 25/07/2017).

Right hemicolectomy, left hemicolectomy, anterior resection, low anterior resection, abdominoperineal resection or total colectomy procedures were performed open or laparoscopically according to localization of the tumor. Loop ileostomy, end ileostomy, end colostomy and/or mucosal fistula procedures were also added if it was necessary.

Patients Five hundred sixty-four patients with American Joint Committee on Cancer (AJCC) stage I-III adenocarcinoma of the colon who had undergone colorectal resection in our department of General Surgery between January 2011-March 2017 were reviewed retrospectively. The patients were divided into two groups according to their surgical conditions: Emergency (Group 1) and elective (Group 2). The inclusion criteria were (1) pathologically confirmed diagnosis of CRC and (2) history of curative surgical colorectal resection. We excluded the patients who had (1) undergone preoperative chemotherapy or radiotherapy, (2) underwent only palliative procedures without resection, such as intestinal decompression or by-pass, (3) had carcinoma in situ (CIS) tumors and/or (4) stage IV disease. Age, sex, place of birth, tumor localization, T classification, N classification, AJCC stage, adequate lymph node yield (≥12 lymph nodes examined), presence of mucinous subtype-lym56

Follow-up Follow-up data were collected from our hospital’s database. Overall survival (OS) was defined as the time from the initial surgical resection until death for any reason. Disease-free survival (DFS) was defined as the time from the initial surgical resection to recurrence or metastasis of CRC. The median duration of follow-up for all cases was 31.3 months (range: 0.1–85.7 months).

Statistical Analysis For discrete and continuous variables, descriptive statistics (mean, Standard deviation, n and percentile) were given. In addition, the homogeneity of the variances, which is one of the prerequisites of parametric tests, was checked through Levene’s test. The assumption of normality was tested using the Shapiro-Wilk test. To compare the differences between three and more groups, one-way analysis of variance was used when the parametUlus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Acar et al. Emergency oncologic colorectal surgery

ric test prerequisites were fulfilled, and the Kruskal Wallis test was used when such prerequisites were not fulfilled. The Bonferroni correction method, which is a multiple comparison test, was used to evaluate the significant results concerning three and more groups. Chi-square test was used for determining the relationships between two discrete variables. When the expected sources were less than 20%, values were determined through the Monte Carlo Simulation Method to include such sources in the analysis. Survival analysis for using the Kaplan-Meier method, the comparison of the variables of the survival times of the factors between the categories was evaluated by the Log Rank Mantel-Cox test. The data were evaluated using SPPS 20 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.). p<0.05 were taken as significance levels.

RESULTS There were 104 (18.4%) patients in group 1 and 460 (81.6%) patients in group 2. Of all patients, 61.2% of the patients were male, and the mean age was 64.27 years. The mean age was 65.8 years in group 1 and 63.9 years in group 2. The distribution of the number of patients according to the years is given in Figure 1. Demographics and clinicopathological features of the patients with CRC are given in Table 1. When two groups were compared, there was a significant difference in age distribution, tumor localization, surgical procedures, AJCC stage, presence of mucinous subtype, lymphovascular and perineural invasion (p<0.05). There was no statistically significant difference between the groups concerning gender distribution and place of birth. The number

Table 1. Demographic and clinicopathological features of patients with colorectal cancer

Group 1 Group 2 (n=104) (n=460) (18.4%) (81.6%)

<50

11 (10.6)

51 (11.1)

50–59

20 (19.2) 103 (22.4)

60–69

31 (29.8) 148 (32.2)

70–79

23 (22.1) 121 (26.3)

≥80

19 (18.3)

0.039*

37 (8)

Gender, n (%)

Female

33 (31.7) 186 (40.4)

Male

71 (68.3) 274 (59.6)

ASA grade

2±1

2±0.9

0.119

RCC

26 (25)

155 (33.7) 0.001

47 (45.2)

285 (62)

N1a

9 (8.7)

29 (6.3)

N1b

8 (7.7)

18 (3.9)

N1c

16 (15.4)

68 (14.8)

N2a

13 (12.5)

24 (5.2)

N2b

11 (10.6)

36 (7.8)

3 (2.9)

72 (15.6)

30 (28.8) 168 (36.5)

10 (9.6)

LCC

61 (58.7) 137 (29.8)

3 (0.7)

RECC

15 (14.4) 162 (35.2)

12 (2.6)

Synchronous tumors

2 (1.9)

6 (1.3)

Right hemicolectomy

25 (24)

147 (31.9) 0.001**

Left hemicolectomy

33 (31.7)

67 (14.6)

Anterior resection

29 (27.9)

77 (16.7)

Low anterior resection

10 (9.6)

121 (26.3)

Abdominoperineal resection

1 (1)

34 (7.4)

Total colectomy

6 (5.7)

14 (3.1)

1 (1)

41 (8.9)

3 (2.9)

45 (9.8)

33 (31.7) 127 (27.6)

28 (26.9)

56 (12.2)

Mucinous subtype, n (%)

Yes

26 (25)

79 (17.2)

92 (75)

367 (82.8)

invasion, n (%) 0.001**

Positive

43 (41.3) 128 (27.8) 0.009**

Negative

61 (58.7) 332 (72.2)

Perineural invasion, n (%)

57 (54.8) 296 (64.3)

Positive

27 (26)

61 (13.3)

43 (41.3)

Negative

77 (74)

399 (86.7)

78 (17)

0.049*

Lymphatic-vascular

T classification, n (%)

0.001**

22 (4.8)

Surgical procedures, n (%)

0.010*

AJCC stage, n (%)

0.2

Tumor location, n (%)

N classification, n (%)

Age, n (%)

Group 1 Group 2 (n=104) (n=460) (18.4%) (81.6%)

0.002**

RCC: Right colon cancer; LCC: left colon cancer; RECC: Rectal cancer; AJCC: American Joint Committee on Cancer; ASA: American Society of Anesthesiologists.

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Acar et al. Emergency oncologic colorectal surgery

The number of patients

100 90 80 70 60 50 40 30 20 10 0

be statistically significant when the groups were compared (p<0.05). Lymphovascular, neural invasion and mucinous subtype were more common in emergency cases.

Group 1 Group 2

The mean numbers of resected lymph nodes and adequate lymph node yield are shown in Table 2.

2011

2012

2013 2014 Year of surgery

2015

2016

Figure 1. he bleeding amount during the operation was significantly less in the open drainage group (105±45 mL vs 315±112 mL, p<0.001).

of patients above 80 years of age was found to be higher in group 1. This difference was also statistically significant. The findings showed that 31.4% of the patients had rectal cancer. Rectum localization was significantly more common in group 2 (p<0.05). In parallel to the tumor localization, there was a significant difference between the groups concerning surgical procedure distribution (p<0.05). Mean tumor diameter was 5.23±3.48 cm, which was 5.47±4.94 cm in group 1 and 4.16±2.64 cm in group 2. Besides, lymph node size is related to the presence of lymph node metastasis. The mean size of positive nodes was 5.6±1.7 mm in group 1, compared with 3.8±0.9 mm group 2. The reason for the statistically significant difference in the T classification, N classification, and AJCC stage between the groups was that the advanced tumors were more frequent among emergency cases. Presence of mucinous subtype, lymphovascular and perineural invasions was detected in 18.6%, 30.3% and 15.6% of the patients, respectively. These components were found to

There was a statistically significant difference between the mean number of the lymph nodes and adequate lymph node yield only in the group of patients who underwent low anterior resection, while no statistically significant difference was found in other surgical procedures. The reason for this higher ratio of group 2 can be explained with the higher number of patients in group 2 and difficulties of rectal surgery. Comparison of demographics and surgical procedures of the patients with adequate lymph node yield are given in Table 3. In 76% of the emergency cases, adequate lymph node yield was performed according to oncological principles, while this ratio was 72.6% in the elective group. According to the tumor localization, there is a significant difference concerning adequate lymph node yield in LCCs of group 1 and RECCs of group 2. It has been observed that there is no effect of age or gender on adequate lymph node yield. The mean duration of hospitalization of all patients was 11.03 days, which was 13.1 in group 1 and 10.5 days in group 2. The presence of ostomy, postoperative complications and advanced-stage disease were found to be the main reasons for this longer duration of hospital stay in the emergency group. Major causes of postoperative complications were anastomotic leak/GIS complication, abdominal abscess, surgical site infection, pneumonia, sepsis, pulmonary failure, venous thromboembolism, gastrointestinal bleeding and hemorrhage.

Table 2. Mean and sufficiency of lymph node yield Surgical procedures

Group 1 (mean lymph node)

Group 2 (mean lymph node)

Right hemicolectomy

18.58

19.74

0.666

Left hemicolectomy

15.12

15.61

0.815

15.17

0.899

Low anterior resection

Anterior resection

14.96

22.10

0.008**

Abdominoperineal resection

16.15

18.63

0.346

Total colectomy

24.75

17.36

0.052

Group 1 (n=104)

Group 2 (n=460)

Sufficiency of lymph node, n (%)

Sufficient (≥12 lymph node yield)

79 (76)

334 (73)

0.576

Deficient (<12 lymph node yield)

25 (24)

126 (27)

0.259

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Acar et al. Emergency oncologic colorectal surgery

Table 3. Compare patients with the sufficiency of lymph node

Group 1 (n=79) (76%)

Group 2 (n=334) (72.6%)

The number of patients

Patients with the sufficiency of lymph node

Survival Function 1.0

<50

8 (10.1)

0.6 0.4 0.2 0.0

Age, n (%)

0.8

45 (13.5)

0.12

50–59

17 (21.5)

74 (22.2)

0.26

60–69

26 (32.9)

102 (30.5)

0.88

70–79

≥80

.00

500.00

1000.00 Time (day)

1500.00

Figure 2. Kaplan-Meier survival analyses of all patients.

15 (19)

87 (26)

0.16

13 (16.5)

26 (7.8)

0.35

1.0 0.8

Survival Function Group 1 Group 2

Female

26 (32.9)

134 (40.1)

0.21

Male

53 (67.1)

200 (59.9)

0.69

Tumor location, n (%)

RCC

25 (31.6)

118 (35.4)

0.88

LCC

45 (57)

92 (27.5)

0.015*

RECC

7 (8.9)

98 (29.3)

0.022*

2 (2.5)

6 (1.8)

0.55

Synchronous tumors

AJCC stage, n (%)

2 (2.5)

43 (12.9)

–

25 (31.6)

130 (39)

0.75

7 (8.8)

14 (4.2)

0.64

2 (0.6)

–

9 (2.7)

–

22 (27.9)

88 (26.6)

0.29

23 (29.2)

47 (14.1)

0.042*

RCC: Right colon cancer; LCC: left colon cancer; RECC: Rectal cancer; AJCC: American Joint Committee on Cancer.

The median duration of follow-up for all participants was 31.3 months (range: 0.1–85.7 months). The recurrence and/ or metastasis rate of 11% (n=62) was observed during the patient follow-up and the majority (n=38) of these recurrent cases were in group 1. The mean survival time was 475.212 days, and the median survival time was 376 days. Kaplan-Meier survival analyses of all patients are shown in Figure 2. Kaplan-Meier survival curves revealed that there was a significant difference between groups (Fig. 3). Poor general condition and electrolyte imbalance of emergency patients are considered to be the reasons for this difference.

DISCUSSION Rectal cancer has the highest-increasing incidence among the digestive tract cancers according to the data of the AmeriUlus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Cumulative Survival

Gender, n (%)

2000.00

0.6 0.4 0.2 0.0 .00

500.00

1000.00 Time (day)

1500.00

2000.00

Figure 3. Kaplan-Meier survival curves of group 1 and group 2.

can Cancer Society (ACS).[12] At present, despite the available colorectal cancer screening programs, many patients must undergo emergency surgery due to colorectal tumors. Smothers et al.[13] mentioned emergency colorectal resection for cancer as the clearest evidence of the failure of screening. We found this bold expression very appropriate since the literature also supports this with the results from the various studies. The rate of emergency CRC surgery is between 6–19% in the countries, such as Germany and Italy, which conduct national screening programs, while it is 22–34% in the countries, such as Spain and Ireland, which do not.[14–16] Our rate of emergency surgery in Turkey for CRC was 18.4%, which was also compatible with the literature since screening programs have been carried out in Turkey for ten years. However, the desired levels have not been reached yet because of the lack of endoscopists and special centers for cancer screening. Thus, colorectal tumors are frequently encountered in the emergency department with bowel obstruction, perforation and bleeding.[10] In their community-based study, Rabeneck et al.[17] reported that factors, such as elder age, low socioeconomic level and difficulty of access to the family physicians, are associated with emergency presentations of CRC. In a study of 3,200 cases by McArdle et al.,[18] it has been shown that non-elec59

Acar et al. Emergency oncologic colorectal surgery

tive patients tend to be at older age and female. Also, Diggs et al.[19] tested whether neighborhood poverty has an effect on emergency surgery in their study, which concluded that zip code and median income were not related to emergency resection. In our study, there was no significant difference concerning gender distribution among the groups, while patients with advanced age were more common in the emergency group. Additionally, there was no significant difference in socioeconomic status (place of birth) among the groups, which may be associated with that each individual in Turkey has equal rights to access health care and opportunity to benefit from the state-supported health services. However, since the evaluation of socioeconomic and intellectual differences is complicated, further studies and surveys should be conducted to understand their impact on CRCsâ&#x20AC;&#x2122; onset. CRCs present differently according to their locations. Since LCCs are more likely to obstruct, emergency surgery is more frequent among them.[20,21] In a multi-center study by Ghazi et al.,[21] only tumor localization was found to be significant when the impacts of sex, age, tumor localization and family history on an emergency or elective surgery were investigated and LCCs were more frequent in the emergency group. Similar to the previous data, the majority of our emergency cases were LCC (especially sigmoid colon), whereas in elective cases, RCC was more common. This resulted in a statistically significant difference in tumor localization among the groups. Non-elective CRCs have been reported to have a more advanced T and N stage according to the AJCC classification. [22] Also, the ability to comply with the oncologic principles under emergency conditions is still controversial today. [8,23,24] The time that passes while trying to keep the resection margins safe and wide, maintaining appropriate lymph node yield and mobilizing the colon may cause physiological deterioration in critical patients, and severe contamination/ inflammation in perforated cases affects the clinicianâ&#x20AC;&#x2122;s choice on practicing the oncologic principles.[25] Mc Ardle et al.[18] showed that oncologic outcomes for CRC could be followed in emergency conditions, and it is associated with long-term survival when it is successful. Likewise, Patel et al.[26] did not find any significant difference between the rates of adequate lymph node yield in elective and non-elective cases, which are reported as 83% and 83.9%, respectively. Our rates of sufficient lymph node yield in elective (73%) and non-elective (76%) groups were also consistent with the literature, and no statistical significance was found. Today, TME is a routine for the treatment of CRC.[27] The quality of the resection in TME is determined with the adequate specimen provided by the surgeon that contains the segment of bowel with disease and its mesentery to the level of the origin of the draining vessels.[8] There are also some 60

other components of a successful TME. These are closely related to the quality of the surgical resection and the pathologic evaluation, tumor features and patient characteristics. Additionally, Panageas et al.[28] revealed that prognostic indicators, such as long-term survival and local failure rates, had been associated with the surgeon and hospital volume. [8] More complete resections for fulfilling oncologic principles may be performed by high-volume surgeons.[29,30] On the other hand, hospital volume also affects the lymph node yield as the results showed that low-volume hospitals were more likely to have fewer than seven lymph nodes evaluated.[31] In our study, a significant difference was only found in RECCs when the mean number of the removed lymph nodes was compared with LCCs. When the age, sex, and AJCC stage were evaluated, there was no significant difference concerning adequate lymph node yield (the difference in stage 3C is thought to be due to the higher number of patients in the emergency group). Lymphovascular invasion, neural invasion and mucinous subtype are poor prognostic factors for CRC.[32] Emergent cases may have these poor histologic characteristics, which are considered to be related with poor disease-free survival (DFS) and overall survival (OS). Therefore, previous evidence suggested that a more aggressive treatment strategy is required for patients with these features.[33,34] Additionally, tumors with mucinous subtype have less sticky and less tight structure since they contain mucinous ponds filled with large cytoplasmic mucin vacuoles, which make these tumors more prone to perforation.[35] Our data are consistent with the literature displaying that lymphovascular- neural invasion and mucinous subtype are more common in the emergency group and related to poor prognosis. Also, perforation was the indication for surgery in 15.4% of the emergency group, and the mucinous subtype was detected in 56.2% of these patients. Emergency resection was independently associated with greater odds of short-term adverse outcomes, including short-term mortality, temporary or permanent colostomy, postoperative complications, intensive care unit requirement, hospitalization time and poorer long-term outcomes.[4,22,36] Preoperative systemic inflammation, which is relatively more severe in emergency cases, may have an impact on the residual tumor cells after the resection leading to an increase in the risk of hospitalization time, recurrence and metastasis. [37] Paulson et al.[10] revealed that almost half of the emergency cases did not undergo a colonoscopy, which is the gold standard for the early detection of anastomotic recurrence and/or synchronous tumors in two years after surgery. Kim et al.[38] found a significant difference in complication rates between elective and emergency colectomies, which were 38.1% and 13.3%, respectively. Additionally, in a study of 118 cases, Ascanelli et al.[24] reported the rates of morbidity and mortality as 27% and 12%, respectively. Manning et al.[39] reported similar outcomes presenting that the emergency Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Acar et al. Emergency oncologic colorectal surgery

group had a median survival of 59 months while the elective group had 82 months. In our study, the mean duration of hospitalization of all patients was 11.03 days, who were 13.1 in the emergency group. Duration of hospital stay, short-term mortality, the incidence of temporary or permanent colostomy and postoperative complications were significantly higher in emergency cases. Also, emergency cases have higher recurrence and shorter DFS rates. This is thought to be due to the higher number of patients with elder age and more advanced stage tumors in the emergency group, presence of sepsis at the time of diagnosis and subsequent systemic inflammation. However, there was not a significant difference in the overall survival between groups. Our study has several limitations. Its retrospective design is the drawback of this study. Furthermore, when using administrative claims data, there is always the possibility of misclassification due to miscoding.

Conclusion We found that 18.4% of the colorectal cancer patients had to undergo emergent colectomies. Although adequate lymph node yield and proper oncologic resection are performed in these patients due to their poor prognostic factors (lymphovascular- neural invasion and mucinous subtype) and severe clinical manifestations (e.g., obstruction and perforation) they have short-term adverse outcomes and worse long-term survival. Therefore, CRC screening guidelines should be developed and disseminated to reduce the rates of emergency surgery and provide a healthier follow-up for the patients.

Acknowledgments The authors thank all the general surgery staff for their cooperation. Ethics Committee Approval: Approved by the local ethics committee (date: 25/07/2017, no: 31829978-050.01. 04-E.1700049773). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: N.A., T.A.; Design: N.A., T.A., E.K.; Materials: T.A., E.K., F.C., K.A.; Data: N.A., T.A., H.K.; Analysis: N.A.; Literature search: N.A., T.A., M.H.; Writing: N.A., T.A., E.K., F.C., H.K.; Critical revision: T.A., K.A., M.H. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87−108.

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2. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9−29. 3. Pruitt SL, Davidson NO, Gupta S, Yan Y, Schootman M. Missed opportunities: racial and neighborhood socioeconomic disparities in emergency colorectal cancer diagnosis and surgery. BMC Cancer 2014;14:927. 4. Amri R, Bordeianou LG, Sylla P, Berger DL. Colon cancer surgery following emergency presentation: effects on admission and stage-adjusted outcomes. Am J Surg 2015;209:246−53. 5. Norwood MG, Sutton AJ, West K, Sharpe DP, Hemingway D, Kelly MJ. Lymph node retrieval in colorectal cancer resection specimens: national standards are achievable, and low numbers are associated with reduced survival. Colorectal Dis 2010;12:304–9. 6. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th Edition of the AJCC Cancer Staging Manual and the Future of TNM. Ann Surg Oncol 2010;17:1471−4. 7. Nelson H, Petrelli N, Carlin A, Couture J, Fleshman J, Guillem J, et al; National Cancer Institute Expert Panel. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst 2001;93:583−96. 8. Chang GJ, Rodriguez-Bigas MA, Skibber JM, Moyer VA. Lymph node evaluation and survival after curative resection of colon cancer: systematic review. J Natl Cancer Inst 2007;99:433−41. 9. Mitchell AD, Inglis KM, Murdoch JM, Porter GA. Emergency room presentation of colorectal cancer: a consecutive cohort study. Ann Surg Oncol 2007;14:1099−104. 10. Paulson EC, Mahmoud NN, Wirtalla C, Armstrong K. Acuity and survival in colon cancer surgery. Dis Colon Rectum 2010;53:385−92. 11. Aquina CT, Becerra AZ, Xu Z, Boscoe FP, Schymura MJ, Noyes K, et al. Nonelective colon cancer resection: A continued public health concern. Surgery 2017;161:1609−18. 12. American Cancer Society. Cancer facts and figures 2016. Atlanta: American Cancer Society; 2016. 13. Smothers L, Hynan L, Fleming J, Turnage R, Simmang C, Anthony T. Emergency surgery for colon carcinoma. Dis Colon Rectum 2003;46:24−30. 14. Bass G, Fleming C, Conneely J, Martin Z, Mealy K. Emergency first presentation of colorectal cancer predicts significantly poorer outcomes: a review of 356 consecutive Irish patients. Dis Colon Rectum 2009;52:678−84. 15. Sjo OH, Larsen S, Lunde OC, Nesbakken A. Short term outcome after emergency and elective surgery for colon cancer. Colorectal Dis 2009;11:733–9. 16. Biondo S, Marti-Rague J, Kreisler E, Parés D, Martín A, Navarro M, et al. A prospective study of outcomes of emergency and elective surgeries for complicated colonic cancer. Am J Surg 2005;189:377−83. 17. Rabeneck L, Paszat LF, Li C. Risk factors for obstruction, perforation, or emergency admission at presentation in patients with colorectal cancer: a population-based study. Am J Gastroenterol 2006;101:1098−103. 18. McArdle CS, Hole DJ. Outcome following surgery for colorectal cancer. Br Med Bull 2002;64:119−25. 19. Diggs JC, Xu F, Diaz M, Cooper GS, Koroukian SM. Failure to screen: predictors and burden of emergency colorectal cancer resection. Am J Manag Care 2007;13:157−64. 20. Snaebjornsson P, Jonasson L, Jonsson T, Möller P, Theodors A, Jonasson JG. Colon cancer in Iceland--a nationwide comparative study on various pathology parameters with respect to right and left tumor location and patients age. Int J Cancer 2010;127: 2645−53. 21. Ghazi S, Lindforss U, Lindberg G, Berg E, Lindblom A, Papadogiannakis N; Low-Risk Colorectal Cancer Study Group. Analysis of colorectal cancer morphology in relation to sex, age, location, and family history. J Gastroenterol 2012;47:619−34.

Acar et al. Emergency oncologic colorectal surgery 22. Wong SK, Jalaludin BB, Morgan MJ, Berthelsen AS, Morgan A, Gatenby AH, et al. Tumor pathology and long-term survival in emergency colorectal cancer. Dis Colon Rectum 2008;51:223−30. 23. Runkel NS, Hinz U, Lehnert T, Buhr HJ, Herfarth Ch. Improved outcome after emergency surgery for cancer of the large intestine. Br J Surg 1998;85:1260−5. 24. Ascanelli A, Navarra G, Tonini G, Feo C, Zerbinati A, Pozza E, et al. Early and late outcome after surgery for colorectal cancer: elective versus emergency surgery. Tumori 2003;89:36−41. 25. Texeira F, Akaishi EH, Ushinohama AZ, Dutra TC, Netto SD, Utiyama EM, et al. Can we respect the principles of oncologic resection in an emergency surgery to treat colon cancer? World J Emerg Surg 2015;10:5. 26. Patel SV, Patel SV, Brackstone M. Emergency surgery for colorectal cancer does not result in nodal understaging compared with elective surgery. Can J Surg 2014; 57:349−53. 27. Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of A 11 years. J Clin Oncol 2012;30:1926−33. 28. Panageas KS, Schrag D, Riedel E, Bach PB, Begg CB. The effect of clustering of outcomes on the association of procedure volume and surgical outcomes. Ann Intern Med 2003;139:658−65. 29. Bui L, Rempel E, Reeson D, Simunovic M. Lymph node counts, rates of positive lymph nodes, and patient survival for colon cancer surgery in Ontario, Canada: a population-based study. J Surg Oncol 2006;93:439–45. 30. Pheby DF, Levine DF, Pitcher RW, Shepherd NA. Lymph node harvests directly influence the staging of colorectal cancer: evidence from a regional audit. J Clin Pathol 2004;57:43−7.

31. Wright FC, Law CH, Last L, Khalifa M, Arnaout A, Naseer Z, et al. Lymph node retrieval and assessment in stage II colorectal cancer: a population-based study. Ann Surg Oncol 2003;10:903−9. 32. Durante AP, Bromberg SH, Barreto E, Cappellano G, Godoy AC. Prognostic value of lymphatic vessel and neural invasion in colorectal carcinoma. [Article in Portuguese] Rev Assoc Med Bras (1992) 2004;50:21−6. 33. Nitsche U, Friess H, Agha A, Angele M, Eckel R, Heitland W, et al. Prognosis of mucinous and signet-ring cell colorectal cancer in a populationbased cohort. J Cancer Res Clin Oncol 2016;142:2357−66. 34. Vallam KC, Desouza A, Bal M, Patil P, Engineer R, Saklani A. Adenocarcinoma of the rectum-A composite of three different subtypes with varying outcomes? Clin Colorectal Cancer 2016;15:47−52. 35. Ghazi S, Berg E, Lindblom A, Lindforss U; Low-Risk Colorectal Cancer Study Group. Clinicopathological analysis of colorectal cancer: a comparison between emergency and elective surgical cases. World J Surg Oncol 2013;11:133. 36. Matsuda A, Miyashita M, Matsumoto S, Matsutani T, Sakurazawa N, Takahashi G, et al. Comparison of Long-Term Outcomes of Colonic Stent as ‘Bridge to Surgery’ and Emergency Surgery for Malignant Large-Bowel Obstruction: A Meta-Analysis. Ann Surg Oncol 2015;22:497−504. 37. Park JH, Watt DG, Roxburgh CS, Horgan PG, McMillan DC. Colorectal cancer, systemic inflammation, and outcome: staging the tumor and staging the host. Ann Surg 2016;263:326−36. 38. Kim J, Mittal R, Konyalian V, King J, Stamos MJ, Kumar RR. Outcome analysis of patients undergoing colorectal resection for emergent and elective indications. Am Surg 2007;73:991–3. 39. Manning AT, Waldron R, Barry K. Poor awareness of colorectal cancer symptoms; a preventable cause of emergency and late stage presentation. Ir J Med Sci 2006;175:55–7.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Acil onkolojik kolorektal cerrahinin başarısından hala şüphe etmeli miyiz?: Geriye dönük çalışma Dr. Nihan Acar, Dr. Turan Acar, Dr. Erdinc Kamer, Dr. Fevzi Cengiz, Dr. Kemal Atahan, Dr. Haldun Kar, Dr. Mehmet Hacıyanlı İzmir Katip Çelebi Üniversitesi Atatürk Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İzmir

AMAÇ: Son yıllarda birçok yayında, kolorektal kanser (KRK) cerrahisinde onkolojik prensiplerin önemi vurgulanmaktadır. Acil ameliyalatların yüksek morbidite ve mortalite oranlarına sahip olduğu bilinmekle birlikte, onkolojik prensipleri sağlamadaki yeterliliği ve prognozu hala tartışmalıdır. Bu çalışmanın amacı, acil ve elektif cerrahi rezeksiyon yapılan KRK hastalarının klinikopatolojik özelliklerini karşılaştırmak, onkolojik ilkelere uygunluğunu ve kısa/uzun dönem sonuçlarını değerlendirmektir. GEREÇ VE YÖNTEM: Kolorektal kanser tanısıyla ameliyat edilen 564 hasta çalışmaya alındı. Hastalar ameliyat koşuluna göre acil (Grup 1) ve elektif (Grup 2) olmak üzere iki gruba ayrıldı. Hastaların demografik, klinikopatolojik özellikleri, prognostik faktörleri ve sağkalımları geriye dönük olarak değerlendirildi. BULGULAR: Grup 1’de 104 (%18.4), grup 2’de 460 (%81.6) hasta vardı. Hastaların %61.2’si erkek ve yaş ortalaması 64.27 idi. Gruplar arası yaş dağılımı, tümör lokalizasyonu, uygulanan cerrahi prosedür, T- N sınıflaması, AJCC evresi, müsin alt tipi, lenfovasküler ve perinöral invazyonu mevcudiyeti açısından istatistiksel önemli farklılıklar mevcut idi. Ortalama tümör çapı 5.23±3.48 cm idi. Gruplar arası, low anterior rezeksiyon yapılan hastalar haricinde, disseke edilen lenf nodu yeterliliği açısından farklılık yok idi. Ortalama sağkalım süresi 475.212 gün ve ortanca sağkalım süresi 376 gündü. Hastalıksız ve genel sağkalım oranları grup 2’de daha yüksek idi. TARTIŞMA: Acil şartlarda ameliyat edilen KRK hastaları, uygun onkolojik rezeksiyon uygulanmasına rağmen, elektif şartlara göre daha kötü kısa ve uzun dönem sonuçlara sahipti. Bu nedenle, acil cerrahi oranlarını azaltmak için kolorektal kanser tarama programlarının yaygınlığının artırılması gerektiğini düşünüyoruz. Anahtar sözcükler: Acil; kolorektal kanser; lenf nodu; morbidite; mortalite; prognoz. Ulus Travma Acil Cerrahi Derg 2020;26(1):55-62

doi: 10.14744/tjtes.2019.04043

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

ORIGIN A L A R T IC L E

High C-reactive protein level as a predictor for appendiceal perforation Ömer Vefik Özozan, M.D.,1

Veli Vural, M.D.2

Department of General Surgery, İstinye Universtity Faculty of Medicine, İstanbul-Turkey

Department of General Surgery, Akdeniz University Faculty of Medicine, Antalya-Turkey

ABSTRACT BACKGROUND: Between 18% and 34% of acute appendicitis (AA) patients may have complicated appendicitis. Perforation is the most important complication of AA. Perforation increases morbidity and mortality. In this study, we aimed to investigate the role of basic inflammatory markers in the diagnosis of perforated AA. METHODS: A retrospective chart review was conducted of patients who underwent appendectomy with a diagnosis of AA between January 2014 and October 2019 at Akdeniz University Faculty of Medicine; and between December 2017 and October 2019 at Istinye University Faculty of Medicine Hospital. Markers recorded were as follows: white blood cell count, neutrophils, lymphocytes, platelets, c-reactive protein, mean platelet volume, red cell distribution width and eosinophils. Hematological indices were combined to generate the following three ratios: white cell neutrophil ratio, platelet lymphocyte ratio and neutrophil-lymphocyte ratio. RESULTS: A total of 536 patients with a diagnosis of AA underwent an operation. There were 344 (64.1%) male patients and 192 (35.9%) female patients. The mean age of the patients was 36.7±16.2 (15-88) years. There were 94 (17.5%) patients with perforated AA and 442 (82.5%) patients with non-perforated AA. C-reactive protein (AUC: 0.81, p<0.001) was the most accurate markers in distinguishing the perforated and non-perforated group. CONCLUSION: Elevated CRP level is a nonspecific inflammatory marker in most of the inflammatory diseases. A high CRP level can, therefore, be used as a supplement in the diagnosis of perforated AA. Keywords: Appendicitis; C-reactive protein; perforation.

INTRODUCTION Acute appendicitis (AA) constitutes approximately 2% of the cases presenting to the emergency service with acute abdominal pain.[1] The first stage in the diagnostic process is the acquisition of the patient’s history, and evaluation of this history together with symptoms and physical examination findings and is often supported by the laboratory and imaging modalities.[2] Between 18% and 34% of the patients may have complicated AA. Perforation is the most important complication of AA.[3] Perforation of the appendix, which increases the risk of abscess formation, wound infection, and sepsis is a major source of morbidity associated with the condition.[2] Early detection of perforation is crucial for the timely appli-

cation of special antibiotic regimens and for estimation of the optimal time point for surgery.[3,4] In the diagnosis of AA, the supplemental roles of ultrasound and computed tomography scans are essential. However, they have a low sensitivity in detecting perforated AA.[5] Thus, there is still the need for a laboratory parameter for prediction of perforation that is inexpensive, readily available, quick, and able to provide high sensitivity and specificity rates.[6] In this study, our aim was to perform an appraisal of inflammatory markers used in the diagnosis of AA and investigate their ability to accurately differentiate between perforated and non-perforated AA.

Cite this article as: Özozan ÖV, Vural V. High C-reactive protein level as a predictor for appendiceal perforation. Ulus Travma Acil Cerrahi Derg 2020;26:63-66. Address for correspondence: Ömer Vefik Özozan, M.D. İstinye Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul, Turkey Tel: +90 212 - 444 66 23 E-mail: omerozozan2002@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(1):63-66 DOI: 10.14744/tjtes.2019.14799 Submitted: 16.11.2019 Accepted: 07.12.2019 Online: 30.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Özozan et al. High CRP level as a predictor for appendiceal perforation

MATERIALS AND METHODS

Statistical Analysis

Patient Data

The Statistical Package for the Social Sciences (SPSS Inc., Chicago, Illinois, USA) version 16.0 for Windows was used for the statistical analyses of the data. Shapiro–Wilk test was used for assessing normality. All values are expressed as mean±standard deviation or counts (percentage) unless otherwise specified. For comparison of two groups, an unpaired, 2-sided Student t-test was used to further evaluate inflammatory marker levels in study groups. We measured the clinical performance of inflammatory markers using receiver operating characteristic (ROC) curves and calculated positive likelihood ratios for cut-point with either high sensitivity and high specificity. The discrimination of a marker is considered perfect if AUC is equal to 1, good if AUC is greater than 0.8, moderate if AUC is 0.6–0.8 and poor if AUC is less than 0.6. A p-value of lower than 0.05 was considered to be statistically significant.

A retrospective chart review was conducted at two academic teaching hospitals of patients who underwent appendectomy with a presumptive diagnosis of acute appendicitis between January 2014 and October 2019. After IRB approval was obtained, ICD-9 code 540.9 (acute appendicitis) was used to procure a list of patient records for the given time frame. The patients who had the diagnosis of AA were hospitalized and undergone surgery. All patients had at least one imaging study ultrasonography (USG) or computed tomography (CT). Final pathology was regarded as a gold standard for the diagnosis of AA. The patients were divided into two groups, Group I was the perforated AA group, and Group II was the non-perforated AA group. The patients with negative appendectomy were excluded from this study.

Recording of Inflammatory Markers and Hematological Ratios

RESULTS

According to hospital protocol regarding patients with suspected AA, inflammatory markers were recorded at admission in Akdeniz University Hospital utilizing a Siemens Advia 2400 and Siemens Advia 2120 hematology and oto analyzer. At Istinye University Hospitalutilizing a Sysmex XN1000, and Roche Cobas 6000 hematology and oto analyzer. Markers recorded were as follows: white blood cell count (WBC), neutrophils, lymphocytes, platelets, c-reactive protein (CRP), mean platelet volume (MPV), red cell distribution width (RDW) and eosinophils. Hematological indices were combined to generate the following three ratios: white cell neutrophil ratio (WNR), platelet lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR).

A total of 536 patients with a diagnosis of AA underwent an operation. There were 344 (64.1%) male patients and 192(35.9%) female patients. The mean age of the patients was 36.7±16.2 (15–88) years. There were 94 (17.5%) patients in Group I and 442 (82.5%) patients in Group II.

Inflammatory Marker Values in Group I and Group II Mean inflammatory marker levels were compared between Group I and Group II. With respect to WBC (p<0.005), neutrophils (p<0.005), CRP (p<0.005), platellets (p<0.005), PLR (p<0.001), MPV (p=0.055) and NLR (p<0.005), mean values

Table 1. Classification of the American Association for the Surgery of Trauma (AAST)[19]

Groups p

Acute appendicitis

Mean

Perforated acute appendicitis

Standard deviation

Mean

Standard deviation

WBC (per mm3) 12399.6 4780.0 14213.8 5120.8 0.001 PLT (per mm3) 246324.7 72896.2 266322.6 113655.7 0.032 NEU (per mm3) 9379.0

4022.0

12277.5

4775.8

0.001

LYM (per mm ) 1778.5 1328.0 1046.5 543.5 0.001 3

NLR PLR

7.1

5.9

14.8 9.5 0.001

177.4 131.9 327.4 229.8 0.001

EOS (per mm3) 177.96 304.03 122.09 109.37 0.001 WNR CRP (mg/L)

1.57 0.33 1.33 0.20 0.159 3.2426

4.5034

11.7666

8.9133

0.001

MPV (femtolitre) 8.09 1.60 8.86 2.66 0.055 RDW (%) 14.21 8.52 13.34 3.12 0.328 WBC: White blood cell count; NEU: Neutrophils; LYM: Lymphocytes; PLT: Platelets; CRP: C-reactive protein; MPV: Mean platelet volume; RDW: Red cell distribution width; EOS: Eosinophils; WNR; White cell neutrophil ratio; PLR: Platelet lymphocyte ratio; NLR: Neutrophil lymphocyte ratio.

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Özozan et al. High CRP level as a predictor for appendiceal perforation

Table 2. ROC analyses Variables

Area

Std. Error

Asymptotic Significance

White blood cell count

.607

.034

.001

95% Confidence Interval Lower Bound

Upper Bound

.540

.674

Platelets

.522 .036

.513

.451

.593

Neutrophils

.679 .032

.000

.616

.742

Lymphocytes

.235 .027

.000

.181

.288

Neutrophil lymphocyte ratio

.789

.027

.000

.736

.842

Platelet lymphocyte ratio

.754

.031

Eosinophils

.414 .033

.000

.694

.814

.009

.349

.478

C-reactive protein

.810

.027

.000

.757

.863

Mean platelet volume

.531

.034

.347

.466

.597

Red cell distribution width

.481

.034

.571

.415

.548

white cell neutrophil ratio

.231

.029

.000

.174

.288

were higher in Group I when compared to Group II (Table 1). The converse was true regarding lymphocytes (p<0.001), RDW (p=0.328), WNR (p=0.159) and eosinophils (p<0.001); mean values were higher in Group II (Table 1).

ROC Curve Analysis ROC curve was employed to evaluate the accuracy of inflammatory markers in distinguishing between group I and group II. Curves representing each inflammatory marker were plotted and compared. CRP (AUC: 0.81, p<0.001) was the most accurate markers in distinguishing the 2 groups (Table 2). Positive likelihood ratio was 2.76 (95% confidence interval, 2.28–3.33) for CRP level more than 35 mg/L.

DISCUSSION Untreated, AA progresses from inflammation to perforation with abscess formation or diffuse peritonitis, making timely operative intervention imperative. Generally, the morbidity and mortality of missing a case of AA with subsequent peritonitis or abscess formation far outweigh the complications associated with a negative appendicectomy.[7,8] Accurate identification of non-perforated AA is topical currently due to emerging evidence suggesting that AA can be managed successfully non-operatively.[6] This study demonstrates that CRP was very accurate in distinguishing between perforated and non-perforated AA. The cut-off points generated in this study may be of future benefit in stratifying these patients when planning their management. Also, part of the difficulty in comparing results arises from the lack of a definite endpoint in patient classification. The current study population was restricted to a defined group of patients who underwent surgery with a clinical diagnosis of AA to eliminate this problem. Several prognostic factors, such as duration of symptoms, Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

pain migration, indirect pain, abdominal guarding, and fever, can be used in combination to predict a possible perforation of the appendix.[8] A systematic review has redfold.[2] It has shown that elevated bilirubin can be used as a prognostic factor for the assessment of perforated AA.[8] C-reactive protein is an important serum inflammatory marker in the diagnosis of AA in the pediatric age group. After 6 to 12 hours of inflammation, the concentration begins to rise and may increase a hundredfold.[2] It was demonstrated that in patients whose symptoms had lasted less than 24 hours, WBC count had a high sensitivity, whereas in those in whom the symptoms had lasted more than 24 hours, CRP had a high sensitivity. However, in a meta-analysis, CRP was shown to have a medium sensitivity (53%–88%) and specificity (46%–82%) for the diagnosis of AA.[7] Ahmed et al.[9] demonstrated that if CRP is more than 48 mg/dL, then, there is an increased risk of perforated AA. A recent study reported that the sensitivity and specificity of CRP to identify perforated AA were 71.0% and 100%, respectively, at this cut-off of 40.1 mg/dL.[10] Another recent study demonstrated that that CRP value >6.15 mg/L has a sensitivity of 100.0% and a specificity of 54% in predicting perforated AA.[11] The results of these studies demonstrate that there is no standard CTP cut-off value for the prediction of perforation. In general, when setting a low cut-off value, this generates a high sensitivity and low specificity and vice versa when setting a cut-off value. Diagnostic scores have been developed in diagnosing acute appendicitis, such as the Alvarado score, RajaIsteri Pengiran Anak Saleha Appendicitis (RIPASA) score and appendicitis inflammatory response score. All of these scores have been proven useful in predicting AA, but none of them evaluate the risk of perforation.[5] USG and CT are the most preferred imaging modalities. In a 65

Özozan et al. High CRP level as a predictor for appendiceal perforation

meta-analysis, Al-Khayal et al.[12] stated that USG had a sensitivity of 83.7% and specificity of 95.9% in cases suspected to have AA. In a similar study, Eng et al.[13] reported the sensitivity and specificity as 83.1% and 90.9%, respectively, for USG, and as 89.9% and 93.6%, respectively, for CT. However, these two techniques have a low sensitivity in detecting perforated AA.[5] On the other hand, despite the higher specificity and sensitivity values, the downside of CT is exposure to ionized radiation. In a study by Smith-Bindman et al.,[14] it was demonstrated that there was an increase in the rate of cancer associated with CTrelated radiation, particularly among young people. In conclusion, we think that although elevated CRP level is a nonspecific inflammatory marker in most of the inflammatory diseases, a high CRP level is helpful in the diagnosis of perforated AA. Ethics Committee Approval: Nil (Retrospective study). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: Ö.V.Ö.; Design: Ö.V.Ö.; Supervision: V.V.; Fundings: V.V.; Materials: Ö.V.Ö., V.V.; Data: V.V.; Analysis: Ö.V.Ö.; Literature search: V.V.; Writing: Ö.V.Ö.; Critical revision: Ö.V.Ö. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Yeşiltaş M, Karakaş DÖ, Gökçek B, Hot S, Eğin S. Can Alvarado and Appendicitis Inflammatory Response scores evaluate the severity of acute appendicitis? TJTES 2018;24:557−62. 2. Çetinkaya E, Erdoğan A, Akgül Ö, Çelik C, Tez M. High serum cancer antigen 125 level indicates perforation in acute appendicitis. Am J Emerg Med 2015;33:1465−7. 3. Hanson KA, Jacop D, Saleh AA, Dissanaike S. In-hospital perforation

risk in acute appendicitis: Age matters. American J Surg. 2019 June 5. doi: https://doi.org/10.1016/j.amjsurg.2019.05.015 [Ahead of print]. 4. Shogilev DJ, Duus N, Odom SR, Shapiro NI. Diagnosing appendicitis: evidence-based review of the diagnostic approach in 2014. West J Emerg Med 2014;15:859−71. 5. Gavriilidis P, de’Angelis N, Evans J, Di Saverio S, Kang P. Hyperbilirubinemia as a Predictor of Appendiceal Perforation: A Systematic Review and Diagnostic Test Meta-Analysis. J Clin Med Res 2019;11:171−8. 6. Beecher SM, Hogan J, O’’Leary DP, McLaughlin R. An Appraisal of Inflammatory Markers in Distinguishing Acute Uncomplicated and Complicated Appendicitis. Dig Surg 2016;33:177−81. 7. Keskek M, Tez M, Yoldas O, Acar A, Akgul O, Gocmen E, et al. Receiver operating characteristic analysis of leukocyte counts in operations for suspected appendicitis. Am J Emerg Med 2008;26:769−72. 8. Burcharth J, Pommergaard HC, Rosenberg J, Gögenur I. Hyperbilirubinemia as a predictor for appendiceal perforation: a systematic review. Scand J Surg 2013;102:55−60. 9. Ahmed N. C-Reactive Protein: An Aid For Diagnosis Of Acute Appendicitis. J Ayub Med Coll Abbottabad 2017;29:250−3. 10. Lai CY, Leung YK, Graham CA. Could C-reactive protein be a potential biomarker of complicated acute appendicitis? Hong Kong J Emerg Med 2014;21:354−60. 11. Choudhary SK, Yadav BL, Gupta S, Kumar N, Bansal S, Kumar Verma P. Diagnostic value of C-reactive protein as a predictor of complicated appendicitis like perforated/gangrenous appendicitis Int Surg J 2019;6:1761−6. 12. Al-Khayal KA, Al-Omran MA, Computed tomography and ultrasonography in the diagnosis of equivocal acute appendicitis. A meta-analysis. Saudi Med J 2007;28:173−80. 13. Eng KA, Abadeh A, Ligocki C, Lee YK, Moineddin R, Adams-Webber T, et al. Acute Appendicitis: A Meta-Analysis of the Diagnostic Accuracy of US, CT, and MRI as Second-Line Imaging Tests after an Initial US. Radiology 2018;288:717−27. 14. Smith-Bindman R, Lipson J, Marcus R, Kim KP, Mahesh M, Gould R, et al. Radiation dose associated with common computed tomography examinations and the associated lifetime attributable risk of cancer. Arch Intern Med 2009;169:2078−86.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Yüksek C-reaktif protein seviyesi apendiks perforasyonu için belirteç olabilir Dr. Ömer Vefik Özozan,1 Dr. Veli Vural2 1 2

İstinye Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul Akdeniz Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Antalya

AMAÇ: Akut apandisit (AA) hastalarının %18 ile %34’ü komplike apandisit tanısı almıştır. AA’nın en önemli komplikasyonu perforasyondur. Perforasyon morbidite ve mortaliteyi arttırır. Bu çalışmada temel enflamatuvar belirteçlerin perfore AA tanısındaki rolünü araştırmayı amaçladık. GEREÇ VE YÖNTEM: Akdeniz Üniversitesi Tıp Fakültesi’nde; Ocak 2014–Ekim 2019 ve Aralık 2017–Ekim 2019 tarihleri arasında İstinye Üniversitesi Tıp Fakültesi Hastanesi’nde AA tanısı ile apendektomi yapılan hastaların retrospektif dosya incelemesi yapıldı. Kaydedilen belirteçler aşağıdaki gibiydi: lökosit sayısı, nötrofil, lenfosit, trombosit sayımı, C-reaktif protein, ortalama trombosit hacmi, kırmızı hücre dağılım genişliği ve eozinofiller. Aşağıdaki üç oranın üretilmesi için hematolojik endeksler çalıştırıldı; beyaz küre nötrofil oranı, trombosit lenfosit oranı ve nötrofil lenfosit oranı. BULGULAR: Akut apandisit tanısı olan toplam 536 hasta ameliyat edildi. Bu hastaların 344’ü (%64.1) erkek ve 192’si (%35.9) kadın idi. Hastaların yaş ortalaması 36.7±16.2 (15–88) idi. Perfore AA olan 94 (%17.5) ve perfore olmayan AA olan 442 (%82.5) hasta vardı. C-reaktif protein (AUC: 0.81, p<0.001), perfore ve perfore olmayan grubun ayırt edilmesinde en doğru belirteç olarak tespit edildi. TARTIŞMA: Yüksek CRP seviyesi, enflamatuvar hastalıkların çoğunda spesifik olmayan bir enflamatuvar belirteçtir, bu nedenle yüksek CRP seviyesi, perfore AA’nın tanısında bir tamamlayıcı olarak kullanılabilir. Anahtar sözcükler: Apandisit; C-reaktif protein; perforasyon. Ulus Travma Acil Cerrahi Derg 2020;26(1):63-66

doi: 10.14744/tjtes.2019.14799

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ORIGIN A L A R T IC L E

The characteristics of the patients in mass public shootings among coup attempt in Turkey: A single-center hospital response Kurtuluş Açıksarı, M.D.,1 Mehmet Koçak, M.D.,2 Görkem Alper Solakoğlu, M.D.,3 Ömer Turan, M.D.,4 Samet Erinc, M.D.,5 Özgür Ekinci, M.D.,6 Ebuzer Aydın, M.D.7 1

Department of Emergency Medicine, İstanbul Medeniyet University Faculty of Medicine, İstanbul-Turkey

Department of Emergency Medicine, Health Science University, Fatih Sultan Mehmet Training and Research Hospital, İstanbul-Turkey

Department of Emergency Medicine, Göztepe Training and Research Hospital, İstanbul-Turkey

Department of Forensic Medicine, İstanbul Medeniyet University Faculty of Medicine, İstanbul-Turkey

Department Orthopedics, Health Science University, Şişli Etfal Training and Research Hospital, İstanbul-Turkey

Department of General Surgery, İstanbul Medeniyet University Faculty of Medicine, İstanbul-Turkey

Department of Cardiovascular Surgery, İstanbul Medeniyet University Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: Turkey is an experienced country for both military and civilian mass casualties that arise from explosions and shootings by various terrorist groups. In this study, we aimed to investigate the characteristics of patient flow admitted to our hospital caused by primarily gunshot wounds during the coup attempts on the 15th of July. METHODS: This descriptive, retrospective study included a total of 50 patients who were injured during a coup attempt on the date of July 15, 2016, and admitted to our emergency department (ED). Demographic characteristics, anatomical injury sites, postoperative clinical outcomes, and hospitalization settings were recorded. The Glasgow Coma Scale (GCS), Trauma and Injury Severity Score (TRISS), Abbreviated Injury Scale (AIS), Revised Trauma Score (RTS) and Injury Severity Score (ISS) were used to measure the severity of injuries. RESULTS: A total of 63 medical personnel voluntarily reached the ED within two hours. Extremity injuries were the most common injuries. The mean RTS, GCS, and TRISS scores did not differ significantly between the patients discharged from the ED and the patients who were hospitalized (p>0.05). However, there was a statistically significant difference in the ISS scores (p<0.001, independent t-test). There was no statistically significant difference in the GCS and RTS scores between the discharged and hospitalized patients, although the ISS scores were higher in hospitalized patients (p>0.05 and p<0.001, respectively). A total of 33 patients (66%) were admitted to the hospital for follow-up and/or surgical intervention. Five (10%) of the patients were hospitalized for more than 14 days. CONCLUSION: The management of each disaster is unique. Armed conflicts result in gunshot wounds, and preparations must be focused on surge capacity and a prolonged hospital stay of the patients. In our study, the length of stay in the hospital decreased after the arrival of volunteer staff to the ED, but we should note that the ISS increased. Hospital disaster plans should be reorganized not only for ED but also for the whole hospital. Keywords: Emergency department; gunshot; injury severity score; mass casualty incidents.

Cite this article as: Açıksarı K, Koçak M, Solakoğlu GA, Turan Ö, Erinc S, Ekinci Ö, et al. The characteristics of the patients in mass public shootings among coup attempt in Turkey: A single-center hospital response. Ulus Travma Acil Cerrahi Derg 2020;26:67-73. Address for correspondence: Kurtuluş Açıksarı, M.D. İstanbul Medeniyet Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, İstanbul, Turkey Tel: +90 216 - 280 33 33 E-mail: kurtulusaciksari@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):67-73 DOI: 10.14744/tjtes.2019.96821 Submitted: 17.07.2019 Accepted: 06.11.2019 Online: 30.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Açıksarı et al. The characteristics of the patients in mass public shootings among coup attempt in Turkey

INTRODUCTION Terrorism is defined as all criminal acts directed against a state. As terrorism sweeps the globe, physicians are obliged to treat patients with a range of injuries requiring a broadening of their skills and knowledge.[1] Mass casualty incidents (MCIs) are often considered infrequent events in developed countries. However, Turkey is an experienced country for both military and civilian mass casualties that arise from explosions and shootings by various terrorist groups, namely the Kurdistan Workers’ Party (PKK), Islamic State of Iraq and Syria (ISIS), and so forth.[2] Turkey faced a coup attempt in which 248 individuals died, and 2,196 wounded across the country on the date of July 15, 2016. Only in Istanbul province, more than 800 individuals were injured, and approximately 90 individuals died.[3] Most relevant places that coup protesters gathered in the east coast of Istanbul were the Bosporus Bridge, which was named as the 15 July Martyrs bridge later, Çengelköy district, and Turk Telekom headquarters where a total of 50 individuals were killed. The trauma mechanisms were mostly shootings, followed by assaults, motor and military vehicle accidents, and falls.[3] Although there are some exceptions, mass casualties arise from terrorist activities tend to cease in a short period.[4] In the present study, we aimed to investigate the wounding patterns of the patients resisting the coup attempt, which caused 12 hours of patient flow to the emergency department (ED) of a tertiary hospital caused by primarily gunshot wounds.

MATERIALS AND METHODS This descriptive, retrospective, clinical study included a total of 50 patients who were injured during the coup attempt on the date of July 15, 2016, and admitted to our ED. Patient records were retrieved from the hospital database. Data, including age, sex, time of admission, type and localization of the injury, relevant clinics to perform surgery, operation types, length of stay (LOS) in the intensive care unit and hospital, blood transfusion requirement, radiological imaging modalities, and reports, were recorded. The Glasgow Coma Scale (GCS), Trauma and Injury Severity Score (TRISS), Abbreviated Injury Scale (AIS), Revised Trauma Score (RTS), and Injury Severity Score (ISS) were used to measure the severity of injuries.[5] This study was approved by the local ethics committee (date: 06.06.2017, no: 2017/0160).

Organization of the ED At the first stage, when the coup attempt began, injured individuals were expected to be admitted to hospitals around Istanbul province. After the confirmation of the event, ED 68

and intensive care units were informed, and the hospital disaster plan was initiated under the leadership of the chief physician. At the second stage, the hospital staff was alerted according to the hospital disaster plan to meet the ED in a coordinated manner. The blood bank was informed, and additional supplies were requested from the hospital repository. In the third stage, the ED was reorganized. Nearly 40 patients who were triaged as green were informed about the event in the waiting area. On the evening of the event, our ED was operating at full capacity (29 beds). To increase capacity in our hospital, the patients who were less critical were either admitted to the available wards or discharged for later follow-up. In the ED, 15 beds in the ward and four beds in the resuscitation area were evacuated. The corridors in the ED were redesigned and prepared as the observation area to be used in case of any need. Green areas for non-serious injuries, yellow for moderate injuries, and red for serious and life-threatening injuries were redefined. The morgue was prepared. Since the events lasted within a relatively brief period, there was no shortage of supplies with available appropriate medical equipment and surge capacity in our hospital. The incident lasted about 12 hours. Ordinarily, in the evening on the date of July 15, 2016, five nurses, five emergency medicine residents, and two emergency medicine specialists were on duty. Sixty-three medical personnel voluntarily reached the ED within three hours between 11:00 PM–02:00 AM. The voluntary healthcare personnel consisted of two emergency medicine specialists, four emergency medicine residents, two orthopedic surgeons, three general surgeons, one anesthesiologist, one plastic surgeon, one cardiovascular surgeon, one family medicine specialist, one chief physician (nephrologist), one pediatric surgeon, one Doctor of Medical History and Ethics, and 28 nurses, eight anesthesia technicians, one midwife, six health officers, one driver, and one clinical support personnel. On July 16, 2016, at 08:00 AM, the shift change was accomplished according to the current schedule, and the volunteer staff arrived at the hospital sustained to work in the hospital until the end of the events was announced.

Statistical Analysis Statistical analysis was performed using the SPSS for Windows version 22.0 software (IBM Corp., Armonk, NY, USA). Descriptive data were expressed in mean±standard deviation (SD), median (min-max), or number and frequency. Normally distributed variables were compared using the Student’s ttest, while non-normally distributed variables were compared using the Mann-Whitney U test. A p-value of <0.05 was considered statistically significant.

RESULTS During the 12-hour period (12:00 AM–12:00 PM of July 16), a total of 151 patients were admitted to our hospital. According to the triage codes, 85, 36, 30 were presented in green, Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Açıksarı et al. The characteristics of the patients in mass public shootings among coup attempt in Turkey

yellow, and red, respectively. Triage codes did not alter during the follow-up of the patients in the ED. Of these patients, 51 were admitted to the hospital due to injuries during the coup attempt. One patient was excluded from this study, as he was found to be dead before the hospital admission. Of the 50 patients, 49 were male and one patient was female with a mean age of 35.38±10.1 (range, 17 to 65) years. Demographic characteristics, anatomical injury sites, postoperative clinical outcomes, and hospitalization settings are shown in Table 1. The most common injury was extremity injury (53%), folTable 1. Clinical characteristics of the victims %

Gender Male

Female

Age (year) 17–29

30–44

45–59

>60

Injured body region

Lower extremity

Upper extremity

Head & neck

Facial

Chest

Abdomen

Gastrointestinal rupture

Discharged directly from ED+

15 30

1–14 days

>14 days

Injury severity scores

Minor injury (ISS 1–8)

Moderate injury (ISS 9–15)

Severe injury (ISS 16–24)

Critical injury (ISS ≥25)

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Figure 1. Hospital arrival time interval of the patients. 120.00%

40 35

100.00%

GCS RTS ISS TRISS (%)

25 20

80.00% 60.00%

40.00%

10 20.00%

5 0

Percentage for TRISS

Maxillofacial

11:45

11:40

07:30 11:00

0 0 09:00 to 11:59

06:00 to 08:59

07:30

Intracranial hemorrhage

00:00 to 02:59

06:30 06:40 06:50 07:00

06:12 06:20

06:05 06:10

0 03:00 to 05:59

06:00 06:04

Fracture / require surgery

06:00

04:20 04:30 05:00 05:30 05:40 05:45

04:00 04:02 04:15

04:00 04:00

Fracture (NOM*/immobilized)

04:00

03:50 03:55 04:00

03:40 03:40 03:45

03:30 03:30

Foreign body excision

03:15 03:20

03:10

03:00

ED: Emergency Department; *NOM: Non-operative management.

02:07 02:30 02:30

Debridement

By feet By ambulance Transferred from another hospital

01:10 02:00 02:05

Transferred from ED to another hospital

Post-operative diagnosis

The total length of stay

The patient flow with injury severity scores is given in Figure 2. The mean GCS scores were 14.6±1.74 (range, 6 to 15). The mean ISS scores were 21.75±10 (range, 1 to 34). A total of 39 patients (78%) had ISS scores fewer than 16; 11 patients (22%) were considered major trauma. The mean RTS, GCS, TRISS scores did not differ significantly between the patients who were discharged from ED and the patients who were

00:30

Of the 15 patients (23.4%) followed in the ED, 12 of them were discharged within eight hours and three within two hours. The ISS scores of these patients were below 4, indicating minor injuries. Three patients who were admitted to the ED were transferred to the external centers after the initial intervention, due to the inadequacy of the operating theaters in the hospital. One patient arrived at 02:07 AM with a deep tendon-muscle-artery cut in the arm, one patient arrived at 03:30 AM with a bullet fragment injuring the femoral artery, and one patient arrived at 04:00 AM with an open wound in the popliteal region. One of these patients was referred back to the referral hospital due to inadequate operating conditions in our hospital.

Values for GCS, ISS and RTS

lowed by head and neck injuries (10%). Nine (18%) of the patients with gunshot wounds were transferred to the hospital by ambulance. Three of these patients were referred from external centers. The majority of the patients with gunshot wounds were admitted to the ED between 03:00 AM–09:00 AM (n=37, 78.7%) (Fig. 1).

0.00%

Time of Arrival

Figure 2. Distribution of the GCS, ISS, RTS, TRISS values according to arrival time.

Açıksarı et al. The characteristics of the patients in mass public shootings among coup attempt in Turkey

(a)

(b)

(c)

Figure 3. Selected radiographic images of wounded patients. (a) A 21-year-old male patient with an anterior-posterior left arm radiograph. Hypodense area (white arrow), which is compatible with the open wound and soft tissue loss, is observed in the left flank. Metallic foreign bodies (black arrows) are observed in the soft tissue. The shrapnel pieces have been verified in debridement of the wound. (b) 21-year-old male patient, bilateral anteroposterior weight-bearing knee radiograph. Metallic foreign bodies compatible with soft tissue loss (white arrow) and shrapnel fragments in soft tissue are observed in the middle distal part of the left thigh (black arrows). There is no pathology in the left femur. (c) A 21-year-old male patient. Three-dimensional computed tomography angiography images show many metallic millimeter-sized foreign bodies (white arrows) in the soft tissue in the distal section of the left knee. Shrapnel pieces have been verified on the wound debridement. Superficial femoral and popliteal arteries are released.

hospitalized (p>0.05). However, there was a positive and significant correlation between the ISS and LOS in the hospital (p<0.001, r=0.912). A total of 33 patients (66%) were admitted to the hospital for follow-up and/or surgical intervention. Five of the patients (10%) were hospitalized for more than 14 days. Eighteen patients (36%) were admitted to the orthopedics, seven (14%) to the plastic and reconstructive surgery, four (8%) to the neurosurgery, one (2%) to the intensive care unit, one (2%) to the general surgery, and one (2%) to the thoracic surgery ward. Based on the postoperative diagnoses, 19 patients (38%) underwent debridement for soft tissue trauma without a vascular injury, and 10 patients (20%) required surgical intervention due to fractures, while six patients (12%) were followed without surgical intervention. There were intracra-

nial hemorrhages in four (8%), vascular injury in four (8%), and gastrointestinal perforation in one patient (2%) who was urgently operated. Figure 3 demonstrates selected radiological images of the patients who had bullet fragments and vascular injuries. The LOS in the hospital and clinical features of patients are shown in Table 2. When the first eight consecutive patients arrived, 12 staff was working in the ED, and the mean ISS scores were 5.75±8.26 (range, 1 to 25. While 75 staff was in the ED, the mean ISS scores of 42 patients who were admitted to the ED were 7.76±8.29 (range, 1 to 34). There were no statistically significant differences in the ISS scores between the two groups (p=0.206). Three patients (37.5%) in the first group and 30 patients (71.4%) in the second group were hospitalized. The mean LOS in the hospital in the first and

Table 2. Characteristics of the patients according to hospital length of stay <24 hr (15 patients)

1–7 days (22 patients)

8–14 days (6 patients)

>14 days (5 patients)

Laseration on face

Foreign body on the extremities*

Multiple bone fractures on feet*

Complicated femur fractures*

Laseration on scalp

Open, dirty wounds on extremities*

Humerus fracture

Subarachonid hemorrhage

Mandibula fracture*

Femur fracture*

Subdural hemorrhage

Toe fracture Laseration on foot

Subdural hemorrhage

Lomber fracture with

with scalp fracture

Metacarp fracture

Gunshut on abdomen

femur fracture

Complicated mandibula

Malleol fractures Bullet hole in the feet,

Scapula fractures

fractures*

Extremity fractures

elbow, shoulder *

More than one patient.

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Açıksarı et al. The characteristics of the patients in mass public shootings among coup attempt in Turkey

Table 3. The comparison of the LOS and Injury Severity Score according to the number of staff in the emergency department

Number of the staff in ED

Number of the Mean patients

Standard Deviation

Minimum

Maximum

12.32

4.04

25.42

0.725

LOS at hospital

11.19

9.16 9.21 1.00 34.42

ISS

5.75 8.26

25 0.206

7.76 8.29

ED: Emergency department; LOS: Total length of stay.

second group was 11.19±12.32 (range, 4.04 to 25.42) days and 9.16±9.21 (range, 1.0 to 34.42) days, respectively, indicating no statistically significant differences between the two groups (p=0.725) (Table 3).

DISCUSSION The MCIs in which many individuals are affected and injured are the events that exceed the ordinary quality/quantity of service provided by emergency medical teams working in the field.[6] The ability of hospital emergency response to major incidents depends on an exceptional incident management system that works well under normal circumstances, adequate supplies, and qualified personnel capable of performing on special occasions.[7] From the view of the MCIs, we consider the events that took place on the date of July 15, 2016 “mega” which affected thousands of people in the society in a limited time and many different focal points, occurring suddenly and constraining the capacity of emergency response in the hospital management.[8] At the time of coup attempt, although communication channels were intact between the Emergency Medicine System (EMS) and our hospital, there were roadblocks on the way of the ambulances, and the victims had difficulties in reaching the hospital on the night of the incident. Therefore, in the first hours of the events, only the wounded in the nearby regions could reach our hospital. After the initial triage at the scene, the injured patients were classified as critical, serious, or mild with a second triage. Not to increase the crowding of the ED during the secondary triage, the triage was performed in a defined area outside the ED[8] using the Simple Triage and Rapid Treatment (START) system.[9] The patient flow pattern expected in disasters is the initial arrival of a large number of mildly injured patients, followed by severely injured ones transferred via the EMS.[10] However, as in our study, in a previous study with burn patients, the patient flow resembling a zigzag pattern according to on the triage scale in a short period was encountered,[11] which can be described as the constant flow of mildly injured patients, in addition to the fewer number of severe injuries admitted at regular time intervals. The zigzag pattern of the patient flow according to the ISS seen in the coup attempt might be due to the collapse of the Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

EMS system and difficulties in reaching the hospital, referral of critical patients from external centers, reorganization of the EMS and redistribution of the patients to other centers after the settlement of events, and prolonged conflict in the 15 July Martyrs Bridge which is located near our hospital. To our knowledge, our study may be the first to evaluate the patients’ admission patterns according to the ISS scores due to firearm injuries. Six patients admitted to our hospital with lifethreatening injuries arrived at 00:30 AM, 03:10 AM, 03:40 AM, 03:50 AM, 04:02 AM, and 05:45 AM, respectively, leading to a peak in the ISS scores. The distribution of the patients with prolonged mass shootings should be explained to the EMS to prevent the transfer of the patients with high ISS scores to the same hospital. In our study, three patients were referred back to the referral hospital due to the lack of operation teams in our hospital to perform specific surgeries. Also, the inability to transfer patients to the ED via EMS for safety reasons led to an increase in the mortality rate. This highlights the importance of effective and on-site intervention of the EMS system, as in the Boston Marathon bombing.[12] Although our hospital covered 10% of all armed injuries, we observed that our patient care quality improved; however, the disaster management principles were violated due to a relatively low number of patients presenting to the ED in a short period. Fifteen patients with a mean ISS score of 4 were followed in the ED setting for eight hours or more. This finding suggests that the emergency follow-up periods of patients for a mass event may longer than expected. The factors of failure to follow disaster medicine principles can be explained by i) the lack of legal regulations for physicians regarding the mass death and injury incidents; ii) physicians’ hesitancy to make decisions independently from the hospital policies; iii) difficulties in discharging patients due to lack of experienced staff; and iv) delayed or failed transfer of mildly injured patients to their residences by ambulances. A study by Cook et al.[13] in the United States of America on firearms between 2004 and 2013 showed that about 30,000 firearm injuries were admitted to hospitals per year, and there was approximately 2,500 death. In addition, the authors reported that males were nine-times more injured than females, 71

Açıksarı et al. The characteristics of the patients in mass public shootings among coup attempt in Turkey

although the mortality rate was higher in female patients. Although both male and female civilians attended the events during the July 15 incidents, the majority of the patients included in our study were males (98%), consistent with the literature. In a literature review of patients who died from gunshot wounds, the mortality rate of the patients was reported to be high and survivable injuries were relatively low. [14] In addition, 58% of the patients had injuries to the head and chest and 20% to the extremities. Chest and head injuries are the most common fatal injuries in 77% of the cases.[14,15] The low mortality rate of the patients who were admitted to our hospital can be explained by the high rate of survivable injuries, as all intracranial hemorrhages arise from a fragmented bullet injury with predominantly extremity injuries. In our study, the LOS in the hospital of the patients admitted to the ED depended on the ISS scores and trauma mechanisms. In the 2008 Mumbai terrorist attack, which can be given as an example of prolonged mass casualty, automatic weapons and explosives were used in four different regions. The terrorist attacks took nearly 60 hours, resulting in the death of 172 citizens with 304 injuries. A total of 62% of the patients were hospitalized in the general surgery, 16% in the orthopedics, 11% in the pediatric, 8% in the plastic surgery, and 1.2% in the brain surgery wards. A total of 38.5% of the patients underwent general surgery and orthopedic interventions, and the in-hospital mortality rate was 12%.[4] The discrepancy between our study and this report can be attributed to the continuation of the mortal injury in the field, with EMS being readily available to the hospital as a result of the siege of the terrorists. In this case, the dead and major injuries were left on the scene due to safety concerns, and more survivable injuries were transferred to the hospital. Therefore, based on our experience, we suggest that hospitalization in orthopedics and plastic wards is relatively higher than in critical areas, such as general and brain surgery. In the Westgate attack, the data were obtained from the patients who applied to the first-level trauma center. The incident took four days and victims were wounded with automatic weapons. As a result, a total of 67 death and 175 injuries occurred. The hospital intervened 65 injured within the first six hours. Twenty-five patients were discharged from the ED, and 45 patients were hospitalized and treated. A total of 63% of the hospitalized patients were operated within the first 24 hours. Thirty patients underwent surgery, and the mean hospitalization duration was five days.[16] These data are consistent with our study, indicating that prolonged duration of mass casualty is associated with higher survival rates due to minor injuries. Therefore, it can be predicted that the number of major and fatal injuries would increase in the first moments of the event, while the number of minor injuries would increase as the incident prolongs. In our study, after the coup attempt was suppressed and the ED started to work normally, the patients who were waiting in the green area at night did not return home and applied to 72

the green area again in the morning. The results of the our talk with the patients revealed that they considered that the hospital was the safest place in the city, and they were able to contact their families and loved ones and did not leave the hospital that affected the surge capacity of the hospital adversely. Of note, hospitals are usually considered the safest places from the point of patients’ views[17] and for the surge capacity of the hospital, it is necessary to plan areas where patients and their relatives can accommodate.[6] In our study, the LOS in the hospital decreased after the arrival of volunteer staff to the ED, even if the ISS increased. We believe that the ability to provide emergency health care during MCIs would increase with volunteers who are trained with standard operational procedures and hospital disaster plans. The limitation of our study was a single-center experience and we are able to evaluate only the patients who came to our hospital.

Conclusion In conclusion, being prepared for MCIs and following the hospital disaster planning codes does not mean that it is completely ready. Of note, the management of each disaster is unique. Planning should be structured to adapt to change situations, considering that unusual events may extend as we experienced and the patient flow according to the severity of injuries may show an unforeseen pattern. As expected, armed conflicts result in gunshot wounds, and preparations must be focused on surge capacity and a prolonged hospital stay of patients. Furthermore, additional trained volunteer support may be needed, when necessary. In our study, the LOS in the hospital decreased after the arrival of volunteer staff to the ED although the ISS increased. We believe that the ability to provide emergency health care during MCIs would increase with volunteers who are trained with standard operational procedures and hospital disaster plans. Further large-scale studies are needed to provide new insights into the emergency health care delivery that has been addressed in this study.

Acknowledgements The authors of this research article would like to thank all medical staff who involved with valuable contributions and efforts during the coup attempt in Turkey. Ethics Committee Approval: Approved by the local ethics committee (date: 06.06.2017, no: 2017/0160). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: K.A., M.K., G.A.S.; Design: K.A., G.A.S.; Supervision: K.A., Ö.T., S.E.; Materials: M.K., A.S., E.A., Ö.E.; Data: S.E., Ö.E.; Analysis: K.A., M.K., G.A.S., E.A.; Literature search: Ö.T., Ö.E., S.E., K.A.; Writing: K.A., E.A., M.K., G.A.S.; Critical revision: K.A., M.K., G.A.S. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Açıksarı et al. The characteristics of the patients in mass public shootings among coup attempt in Turkey

REFERENCES 1. Frykberg ER. Medical management of disasters and mass casualties from terrorist bombings: how can we cope? J Trauma 2002;53:201−12. 2. Rodoplu U, Arnold JL, Tokyay R, Ersoy G, Cetiner S, Yücel T. Masscasualty terrorist bombings in Istanbul, Turkey, November 2003: report of the events and the prehospital emergency response. Prehosp Disaster Med 2004;19:133−45. 3. Tayfur İ, Afacan MA, Erdoğan MÖ, Çolak Ş, Söğüt Ö, Genç Yavuz B, et al. Health results of a coup attempt: evaluation of all patients admitted to hospitals in Istanbul due to injuries sustained during the July 15, 2016 coup attempt. TJTES 2018;24:39−42. 4. Roy N, Kapil V, Subbarao I, Ashkenazi I. Mass Casualty Response in the 2008 Mumbai Terrorist Attacks. Disaster Med Public Health Prep 2011;5:273−9. 5. Bilgin NG, Mert E, Camdeviren H. The usefulness of trauma scores in determining the life threatening condition of trauma victims for writing medical-legal reports. Emerg Med J 2005;22:783−7. 6. Peleg K, Michaelson M, Shapira SC, Aharonson-Daniel L. Principles of emergency management in disasters. Adv Ren Replace Ther 2003;10:117−21. 7. American College of Emergency Physicians. Health care system surge capacity recognition, preparedness, and response. Ann Emerg Med 2005;45:239. 8. Hammond J. Mass Casualty Incidents: planning implications for trauma

care. Scand J Surg 2005;94:267−71. 9. Kahn CA, Schultz CH, Miller KT, Anderson CL. Does START triage work? An outcomes assessment after a disaster. Ann Emerg Med 2009;54:424−30, 430.e1. 10. Li GQ, Hou SK, Yu X, Meng XT, Liu LL, Yan PB, et al. A descriptive analysis of injury triage, surge of medical demand, and resource use in an university hospital after 8.12 Tianjin Port Explosion, China. Chin J Traumatol 2015;18:314−9. 11. Chen SY, Chaou CH, Ng CJ, Cheng MH, Hsiau YW, Kang SC, et al. Factors associated with ED length of stay during a mass casualty incident. Am J Emerg Med 2016;34:1462−6. 12. Gates JD, Arabian S, Biddinger P, Blansfield J, Burke P, Chung S, et al. The initial response to the Boston marathon bombing: lessons learned to prepare for the next disaster. Ann Surg 2014;260:960−6. 13. Cook A, Osler T, Hosmer D, Glance L, Rogers F, Gross B, et al. Gunshot wounds resulting in hospitalization in the United States: 2004-2013. Injury 2017;48:621−7. 14. Smith ER, Shapiro G, Sarani B. The profile of wounding in civilian public mass shooting fatalities. J Trauma Acute Care Surg 2016;81:86−92. 15. Seçer M, Ulutaş M, Alagöz F, Uçkun ÖM, Çınar K, Yel C, et al. Relationship of biological factors to survival in spinal gunshot injuries. TJTES 2016;22:253−8. 16. Wachira BW, Abdalla RO, Wallis LA. Westgate Shootings: An Emergency Department Approach to a Mass-casualty Incident. Prehospital Disaster Med 2014;29:538−41. 17. Smilowitz R, Blewett W, Williams P, Smilowitz W. Risk Management Series, Safe Rooms and Shelters. FEMA; 2006.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Türkiye’de darbe girişimi esnasında kitlesel silah yaralanmasına maruz kalan hastaların özellikleri: Tek merkezli hastane deneyimi Dr. Kurtuluş Açıksarı,1 Dr. Mehmet Koçak,2 Dr. Görkem Alper Solakoğlu,3 Dr. Ömer Turan,4 Dr. Samet Erinc,5 Dr. Özgür Ekinci,6 Dr. Ebuzer Aydın7 İstanbul Medeniyet Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, İstanbul Sağlık Bilimleri Üniversitesi Fatih Sultan Mehmet Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, İstanbul Göztepe Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, İstanbul 4 İstanbul Medeniyet Üniversitesi Tıp Fakültesi, Adli Tıp Anabilim Dalı, İstanbul 5 Sağlık Bilimleri Üniversitesi Şişli Etfal Eğitim ve Araştırma Hastanesi, Ortopedi Kliniği, İstanbul 6 İstanbul Medeniyet Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul 7 İstanbul Medeniyet Üniversitesi Tıp Fakültesi, Kalp ve Damar Cerrahisi Anabilim Dalı, İstanbul 1 2 3

AMAÇ: Türkiye, bombalama ve ateşli silah eylemleri gibi terörist saldırılarından kaynaklanan askeri ve sivil kitlesel yaralanmalar konusunda deneyimli bir ülkedir. Bu çalışmada, 15 Temmuz 2016’da gerçekleşen darbe girişiminde, ön planda ateşli silah yaralanmaları nedeniyle hastanemize başvuran hastaların ve hasta akışının özelliklerini araştırmayı amaçladık. GEREÇ VE YÖNTEM: Bu tanımlayıcı, geriye dönük çalışmamıza 15 Temmuz 2016 tarihinde darbe girişimi sırasında yaralanan ve acil servisimize başvuran toplam 50 hasta alındı. Hastaların demografik özellikleri, anatomik yaralanma bölgeleri, ameliyat sonrası klinik sonuçları ve hastanede yatış özellikleri araştırıldı. Yaralanma şiddetini ölçmek için Glasgow Koma Skoru (GCS), Travma ve Yaralanma Şiddet Skoru (TRISS), Kısaltılmış Yaralanma Skoru (AIS), Düzeltilmiş Travma Skoru (RTS) ve Yaralanma Şiddet Skoru (ISS) kullanıldı. BULGULAR: Hastaların tamamına yakını erkekti (49:1). En sık yaralanma, ekstremite yaralanmasıydı (%53). Acil servisten taburcu edilen hastalar ile hastaneye yatırılan hastaların RTS, GCS ve TRISS skorları ortalamaları arasında istatistiksel anlamlı bir fark saptanmazken (p>0.05), ISS skoru hastanede yatanlarda daha yüksek saptandı (p<0.001). Takip ve/veya cerrahi girişim nedeniyle hastaneye yatırılan toplam 33 (%66) hastanın beşi (%10) 14 günden uzun süre hastanede takip edildi. Acil serviste 12 personelin çalıştığı ilk dönemde ISS skor ortalaması 5.75±8.26 olan sekiz hasta başvurdu. Bu hastaların üçü (%37.5) hastaneye yatırıldı. İki saat içinde acil servise gönüllü olarak 63 sağlık çalışanı ulaştı. Acilde 75 personelin çalıştığı dönemde ISS skor ortalaması 7.76±8.29 olan 42 hasta başvurdu. Otuz hastanın yatışı yapıldı (%71.4). İlk ve ikinci grubun hastanede yatış süreleri (HYS), sırasıyla 11.19±12.32 gün ve 9.16±9.21gün olarak saptandı. Personel sayısının artmasıyla HYS’de azalma görüldü ancak bu azalma istatistiksel olarak anlamlı değildi (p=0.725). TARTIŞMA: Her afetin yönetimi kendine özgüdür. Ateşli silah yaralanması hazırlıklarında hastanenin yüklenme kapasitesine ve hastaların hastanede uzamış yatış süresine odaklanılmalıdır. Çalışmamızda, gönüllü personellerin acil servise ulaşması ile birlikte ISS skorları yüksek olan yaralıların hastanede kalış sürelerinin kısaldığı tespit edilmiştir. Kitlesel olaylarda, acil sağlık hizmetlerinin standart operasyonel prosedür eğitimi almış gönüllülerle artacağına inanıyoruz. Hastane afet planları, sadece acil servisler için değil tüm hastane için yeniden düzenlenmelidir. Anahtar sözcükler: Acil servis; ateşli silah; kitlesel yaralanma olayları; yaralanma şiddet skoru. Ulus Travma Acil Cerrahi Derg 2020;26(1):67-73

doi: 10.14744/tjtes.2019.96821

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

ORIGIN A L A R T IC L E

Investigation of firearm injury cases presented to training and research hospital’s emergency service Orhan Meral, M.D.,1 Caner Sağlam, M.D.,2 Birdal Güllüpınar, M.D.,2 Özlem Ezgi Aktürk, M.D.,2 Serdar Beden, M.D.,2 İsmet Parlak, M.D.3 1

Department of Forensic Medicine, University of Health Sciences İzmir Bozyaka Training and Research Hospital, İzmir-Turkey

Department of Emergency Medicine, University of Health Sciences İzmir Bozyaka Training and Research Hospital, İzmir-Turkey

Department of Emergency Medicine, Aksaray University Training and Research Hospital, Aksaray-Turkey

ABSTRACT BACKGROUND: Firearm injuries are criminal events that may cause severe morbidity and mortality and concerned with Emergency Medicine and Forensic Medicine. The present study aims to evaluate the wound characteristics of the cases who presented to emergency services due to firearm injuries. METHODS: In this study, 213 patients who were 18 years of age or older who applied to the Sağlık Bilimleri University Bozyaka Training and Research Hospital Emergency Service with gunshot injury were included. RESULTS: Of the 213 cases examined, 182 (85.4%) were male. The ages of the cases ranged from 18 to 78 years, and the mean age was found as 33.2±12.6. The most common months were April (n=28, 13.2%) and May (n=25, 11.6%). The findings showed that 194 (91.1%) of 213 patients were discharged after completing the treatment in the hospital, and 19 patients (8.9%) died despite all interventions. CONCLUSION: Our study presents an important cross-section of the gunshot injury patterns and their consequences in Turkey, but it contains regional data. In this regard, multicentre and multidisciplinary studies covering the country, in general, are considered to be a significant contribution to the literature. Keywords: Emergency; firearm injury; morbidity; mortality.

INTRODUCTION Firearms are weapons used for defense or assault, which are capable of throwing bullets into the distance with the gunpowder gas pressure.[1] They may cause a wide range of damage from simple soft tissue trauma to a fatal internal organ and vascular injuries.[2,3] Firearm injuries may occur as a result of accidental or homicidal/suicidal actions.[4] The severity of the injury depends on the type of firearm and the distance between the firearm and the body part, which is shot.[3,5,6] Thus, rapid evaluation and treatment of gunshot wounds, especially in case of serious injuries, within the golden hour is of vital importance.[7,8]

Emergency Department care of the firearm injury patient begins with an initial assessment for potentially serious injuries. A primary survey is undertaken quickly to identify and treat immediately life-threatening conditions, with simultaneous resuscitation and treatment. Specific injuries that should be immediately identified and addressed during the primary survey include airway obstruction, tension pneumothorax, massive internal or external hemorrhage, open pneumothorax, flail chest, and cardiac tamponade.[9] This study aims to evaluate the relationship between morbidity and mortality and wound characteristics of firearm injury cases presenting to emergency service. We expect that this study may contribute to the national and international literature.

Cite this article as: Meral O, Sağlam C, Güllüpınar B, Aktürk ÖE, Beden S, Parlak İ. Investigation of firearm injury cases presented to training and research hospital’s emergency service . Ulus Travma Acil Cerrahi Derg 2020;26:74-79. Address for correspondence: Orhan Meral, M.D. Sağlık Bilimleri Üniversitesi İzmir Bozyaka Eğitim ve Araştırma Hastanesi Adli Tıp Kliniği, İzmir, Turkey Tel: +90 232 - 250 50 50 / 5832 E-mail: orhanmeral@ymail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):74-79 DOI: 10.14744/tjtes.2019.08949 Submitted: 07.01.2019 Accepted: 14.02.2019 Online: 30.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Meral et al. Investigation of firearm injury cases presented to training and research hospital’s emergency service

MATERIALS AND METHODS Our study is retrospective and cross-sectional study. In this study, 213 patients who were 18 years of age or older who presented to the Sağlık Bilimleri University Bozyaka Training and Research Hospital Emergency Service with gunshot injury were included. The demographic characteristics, such as age and gender of the cases, the type of gun used, the date of the incident, the time of presentation to the emergency service, the blood alcohol level of the patient, injury findings of the patient, and requested specialty consultations, were retrieved from the medical records. Forensic medical evaluation of the injuries was made. Cleaning wounds and dressing were accepted as simple medical interventions. Wound debridement or bullet removal, as well as injuries like bone fractures or internal organ damage, were not considered to be simple wounds. Our work was carried out in accordance with the Helsinki Declaration and approved by the Ethics Committee (date: 08.11.2016, no: 2).

Statistical Analysis Demographic data were expressed as mean ± standard deviation and/or percentage. The SPSS version 22.0 for Windows (Statistical Software, Chicago, IL, USA) was used for statistical analysis, and Chi-square and Fisher’s exact tests were conducted for data comparison. The comparison values were calculated at a 95% confidence interval; p<0.05 was considered statistically significant.

Limitations Due to the lack of a childhood trauma unit in the hospital where this study was conducted, there were no cases under 18 years old in this study. Other limitations, including the retrospective nature of the study, and the inadequacy of medical records, make it impossible to comment on the nature of the incidents (accident/suicide/homicide).

RESULTS Of the 213 patients who were included in this study within the 5-year period of this study, 182 (85.4%) of them were male. The ages of the cases ranged from 18 to 78 old years, and the mean age was found as 33.2±12.6. The demographic data of the cases are summarized in Table 1. When the dates that firearm injuries took place were examined, the most frequent months of occurrence were April (n=28, 13.2%) and May (n=25, 11.6%). The findings showed that admissions to the hospital were more frequent between 18:01–24:00 (n=78, 36.6%) (Table 2). Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Table 1. Demographic data

Female

14.6

Male

182

85.4

Gender

Age range of subjects

18–78

Mean age of subjects (years) 33.2±12.6 Age groups (year) 18–30

106

49.8

31–40

24.0

41–50

13.1

51–60

10.8

2.3

61 and over

Table 2. Date of event and cases of hospital admissions

2011

21.1

2012

13.6

2013

13.6

2014

23.9

2015

27.8

7.0

February

3.8

March

4.7

April

13.2

May

11.6

June

9.4

July

8.5

August

8.0

September

8.0

October

7.5

November

9.4

December

8.9

00:01–06:00

27.7

06:01–12:00

12.2

12:01–18:00

23.5

18:01–24:00

36.6

Distribution of firearm injuries by year

Distribution of firearm injuries by month January

Distribution of firearm injuries by the time period of a day

When the types of firearms were examined, it was found that 160 (75.1%) of the cases were by pistol, and 53 cases (24.9%) were injured by hunting rifles. 75

Meral et al. Investigation of firearm injury cases presented to training and research hospitalâ&#x20AC;&#x2122;s emergency service

Table 3. Distribution of consulted specialties Clinics

n=37 (15.0%)

n %

Orthopedic & traumatology

114

53.2

General surgery

15.9

Neurosurgery

26 12.1

Cardiovascular surgery

Others*

17 8.0

Total

n=4 (1.6%) n=19 (7.7%) n=28 (11.3%)

n=41 (16.6%)

n=16 (6.5%)

10.8

214 100.0

More than one area of injury was seen in 31 cases, the total number of injury zones (n=247) is greater than the number of cases (n=213), the proportion is based on the number of injuries.

n=102 (41.3%)

*Ophthalmology (6), thoracic surgery (4), otorhinolaryngology (2), plastic surgery (2), anesthesia (2), urology (1).

Figure 1. Distribution of injury zones.

Table 4. Distribution of hospitalization by specialties Clinics

n %

Orthopedic & traumatology

46.6

General surgery

28.6

Neurosurgery

16.2

8.6

Others* Total

105 100.0

*Ophthalmology (4), cardiovascular surgery (2), otorhinolaryngology (1), thoracic surgery (1), plastic surgery (1).

The findings showed that 182 (85.4%) of the cases were injured on one single body region while 31 (14.6%) cases were injured on more than one body region. The total number of injured body regions was 247, and the most common injuries were lower-extremity injuries (n=102, 41.3%). The distributions of the injury zones are shown in Figure 1. The findings showed that 36 of the cases (16.9%) had their blood alcohol levels measured in Emergency Service, and all of the cases were reported to the judicial authorities after the initial or emergency management. In 46 cases (21.6%), no specialty consultation was requested while for the other 167 cases (78.4%), other specialties were consulted 214 times in total, and most of them were made to the Orthopedics & Traumatology department (n=114, 53.2%) (Table 3). After forensic medicine evaluation was made, it was concluded that 48 patients (22.5%) suffered a life-threatening injury, 33 patientsâ&#x20AC;&#x2122; injuries (15.5%) were mild enough to be treated by simple medical intervention, and the remaining 132 cases (62%) were found not to have life-threatening injury but also not to be mild enough to be treated by simple medical intervention. It was found that 97 cases (45.5%) were discharged from the emergency department, 105 cases (49.3%) were hospitalized, 76

After Interventions in Emergency Medicine

Death* (n=11, 5.2%)

Clinic Admission (n=105, 49.3%)

Death* (n=8, 7.6%)

Discharge (n=97, 45.5%)

Discharge (n=97, 92.4%)

Figure 2. Situation for the casesâ&#x20AC;&#x2122; post-interventions in hospital. *Of the 19 patients who died, 14 had head and brain injuries, two patients had abdominal and internal organ injuries, and three patients had chest and lung injuries. In addition, all the patients who died were followed up in intensive care units and six patients were operated.

and 11 cases (5.2%) died despite all interventions made in the emergency service. Most of the cases were hospitalized in the Department of Orthopedics & Traumatology (n=49, 46.6%) (Table 4), and 61 of the 105 patients who were hospitalized (58.1%) underwent surgery. Of the 213 patients included in this study, 194 (91.1%) were discharged after completing their treatment in the hospital, but 19 patients (8.9%) were found to have died despite all interventions (Fig. 2). Complications occurred in seven patients during the followup period after hospitalization. Upper extremity amputation was performed in one patient, lower-extremity amputation was performed in one patient, and splenectomy was performed in one patient. In addition, paraplegia was developed due to medulla spinalis injury in one patient and permanent eye and vision loss were observed in three patients. When the relationship between death and injured body regions was examined, it was determined that 14 (37.8%) of the 37 patients who had head injuries died (p<0.001). None of the 41 patients who were injured on the upper extremity and none of the 102 patients who were injured on the lowerextremity died (p<0.001). No statistically significant relationUlus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Meral et al. Investigation of firearm injury cases presented to training and research hospital’s emergency service

ship was found between the number of deaths and the other body regions of injuries, the total number of injured body regions, and the type of firearm used (p>0.05).

DISCUSSION Due to its easy availability and portability, there is a steady increase in firearm injuries and deaths in our country and the world.[6,7] From this point of view, gunshot wounds and deaths have become an important public health problem, and at the same time, it also carries a judicial event feature.[1,6] The high number of male in the cases of firearm injuries had been found to be related to that males are more likely to take part in criminal events and also they reach these weapons more easily.[1,10] In our study, most of the cases (n=182, 85.4%) were male and most frequently were in the 18-30 age group (n=107, 49.8%). This finding is consistent with many studies in our country and other countries.[7,10–14] In addition, it is seen that firearm injuries are a risk factor of death for almost all ages when examination made in our study in which patients’ ages changed between 18–78 and also in other studies. The most frequent months of occurrence were April (n=28, 13.2%) and May (n=25, 11.6%). Admissions to the hospital were more frequent between 18:01–24:00 (n=78, 36.6%). Although it is seen that there is a difference between the studies about in which months patients admitted to the hospital mostly, Türkoglu’s study[10] reported that events occurred most often in May, similar to our study. Due to the differences in the scientific research conducted, it is thought that there is not enough explanation about why more people are suffering during April and May. Studies indicate that pistols are the most common type of firearm, resulting in death.[1,10,11] In our study, the majority of firearm injuries were found to have occurred by pistols (n=160, 75.1%). Long-barreled weapons have been reported to be used more frequently in the studies performed by Kahramanmaraş[14] and Elazığ.[10] It is thought that the terrorist events are seen more in these regions due to their geographical location, leading to this result. In our study, the findings showed the most common injuries were on the lower extremity (n=102, 41.3%), followed by the upper extremity (n=41, 16.6%). In the studies conducted by Karaca[7] and Tokdemir,[11] extremity injuries were the most common, but the head and neck injuries were reported more frequently in Cingöz,[1] Erkol,[14] Kır[12] and Türkoğlu[10] studies. The studies which found the head and neck region injuries to be more frequent are the studies that were conducted on the autopsy cases. This is anticipated as head and neck injuries are often more likely to cause death. Physicians have medical and legal obligations, as well as administrative and judicial obligations. Since firearm injury cases Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

are also forensic cases,[6] judicial authorities should be notified about these cases by reports according to the 280th article of the Turkish Penal Code.[15] If the notification is not made, there may be an investigation by the judicial authorities regarding “not reporting a crime”. In our study, blood alcohol levels were checked only in 16.9% (n=36) of the cases, and all of the cases were reported to the judicial authorities (n=213). From this point of view, the obligation to report when encountered this kind of judicial event is fulfilled in the hospital where the examination is made. Along with this, although blood alcohol level checking for all firearm injury cases is not compulsorily enforced by legal regulations or judicial decisions. It is also thought that the level of blood alcohol should be examined in all firearm cases to protect physicians from allegations that may arise in the future and to prevent possible grievances. Patients with firearm injuries are considered as multi-trauma patients. Thus, a comprehensive physical examination is mandatory. After the evaluation of the consultant physicians, the decision to admit or discharge a patient is given. Although there are no definitive criteria, all the following criteria may be used for the evaluation of firearm injuries cases: All penetrating head, thorax and abdominal injuries, history of prolonged loss of consciousness, deterioration in the level of consciousness, moderate to severe headache, significant alcohol/drug intoxication, multiple bone fractures, cerebrospinal fluid leakage (rhinorrhea or otorrhea), significant associated injuries, no reliable companion at home, abnormal Glasgow Coma Scale score, focal neurologic deficits, abnormal Computer Tomography scan, unavailable Computer Tomography scan.[16] In our study, for patients with firearm injury, the most commonly consulted specialty was the Orthopedics & Traumatology Department (n=114, 53.2%). Patients were also most frequently admitted to the Orthopedics & Traumatology Department (n=49, 46.6%). This situation was found usual because injuries were seen mostly in extremities. Injuries from firearms are increasing in our country and in the world and also form an important part of all injuries.[8,9] Thus, attention has been drawn to the necessity of strict measures for the control of firearms, as well as to increase public awareness using media and other social networks.[1] After forensic medicine evaluation was made, it was concluded that 48 patients (22.5%) suffered a life-threatening injury, 33 patients’ injuries (15.5%) were mild enough to be treated by simple medical intervention, and the remaining 132 cases (62%) were found not to have life-threatening injury but also not to be mild enough to be treated by simple medical intervention. In addition, 61 of 105 patients (58.1%) who were hospitalized to the related clinics underwent surgery. Tokdemir’s study on 304 cases with firearm injuries in Elazığ[11] also reported that 43% of the cases were exposed to life-threatening situations, which shows the importance of morbidity and mortality of firearm injuries. 77

Meral et al. Investigation of firearm injury cases presented to training and research hospital’s emergency service

It was determined that 194 cases (91.1%) were discharged after completing their treatment in the hospital (97 cases of them discharged from the Department of Emergency), but 19 patients (8.9%) died despite all interventions (11 cases of them have died in Emergency Department). In Karaca’s study[7] held in Ankara, the findings showed that 24 of the 142 cases (16.9%) died. There are many factors affecting morbidity and mortality in firearm injuries. Although bullets cause small holes in the skin, serious injuries may occur in the body, especially in the head, chest and abdomen. Because of these possible injuries, studies emphasized the importance of rapid and effective evaluation in the early stages.[2,7] In our study, complications occurred in seven patients during the follow-up period after hospitalization. Upper extremity amputation was performed in one patient; lower-extremity amputation was performed in one patient, and splenectomy was performed in one patient. In addition, paraplegia was developed due to medulla spinalis injury in one patient, and permanent eye and vision loss were observed in three patients. Complications related to gunshot wound cases depend on the location and severity of the injury. Injuries affecting the nervous system and causing long-term neurological damage are especially important.[7]

When forensic medical evaluation made, the findings showed that 19 of them (8.9%) died despite all interventions. As the availability of firearms becomes easier, it is inevitable that injuries and deaths due to this will occur more frequently. To prevent unauthorized weapons from being procured, to keep the legal regulations related to the possession of weapons and carrying licenses in sight, to maintain strict follow-up, control and control after the license acquisition, as well as to increase deterrent criminal sanctions, especially in civil society organizations, media and other social networks to inform and raise awareness of the community on these issues will contribute to the reduction of firearm injuries and deaths. Our study presents an important cross-section of the gunshot injury patterns and their consequences in Turkey, although this study only contains regional data. Although firearm injuries and deaths are a serious public health problem, which is an important factor in all injuries and deaths, there is no multicentered study covering the country in general. Thus, multicentered and multidisciplinary studies that reflect the country’s situation as a whole are needed. Ethics Committee Approval: Approved by the local ethics committee (date: 08.11.2016, no: 2). Peer-review: Internally peer-reviewed.

When the relationship between death and injured body regions is examined, the findings showed that 14 (37.8%) of the 37 patients who were injured on the head died (p<0.001). None of the 41 patients who were injured on the upper extremity and none of the 102 patients who were injured on the lower-extremity died (p<0.001), which was found statistically significant. Firearms may lead to serious fatal head injuries as they cause brain and large vessel injuries, as well as skull fractures, but when in the extremities, these wounds may be fatal only in case of major vessel injuries. From this point of view, the data we have obtained in our study are considered normal.

Conclusion and Recommendations In our study, the majority of cases (n=182, 85.4%) were male, their ages ranged from 18 to 78, and the most frequent group was 18 to 30 years (n=107, 49.8%). The findings suggest that males often play a major role in criminal matters because of easy access to firearms, although firearm injuries are a risk factor for almost all ages. Physicians have medical and legal obligations, as well as administrative and judicial obligations. Since thee firearm injury cases are also forensic cases, these cases should be reported to the judicial authorities. In our study, all cases presented to emergency services were reported to the judicial authorities by physicians to fulfill the obligations. Physicians should follow legislation regularly in forensic medical issues to prevent future allegations and grievances in judicial cases, so it would be appropriate for physicians to participate in the training in this regard. 78

Authorship Contributions: Concept: O.M.; Design: O.M., C.S.; Supervision: O.M., C.S., B.G., İ.P.; Fundings: O.M., C.S., B.G., İ.P.; Materials: O.M., Ö.E.A., S.B.; Data: O.M., Ö.E.A., S.B.; Analysis: O.M., Ö.E.A., S.B.; Literature search: O.M., C.S., B.G.; Writing: O.M., C.S., B.G., Ö.E.A, S.B., İ.P.; Critical revision: C.S., B.G., İ.P. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Cingöz G, Erel Ö, Dirlik M, Özkök MS, Katkıcı U. Deaths due to gunshot wounds in city of Aydın. The Bulletin of Legal Medicine 2010;15:84−90. 2. Oymacı E, Kapkaç M, Uçar Y, Ertan H, Özdedeli E, Tokat Y. The effects of gunshot and shotgun wounds to mortality and morbidity. Turkish J Trauma Emerg Surg 1997;3:132−6. 3. Vij K. Textbook Forensic Medicine and Toxikology, Principles and Practice. 5th Ed. India: Elsevier; 2011. 4. Shkrum MJ, Ramsay DA. Forensic Pathology of Trauma. New Delhi: Humana Press; 2007. 5. Stefanopoulos PK, Hadjigeorgiou GF, Flippakis K, Gyftokostas D. Gunshot wounds: A review of ballistics related to penetrating trauma. Journal of Acute Disease 2014;3:178−85. 6. Beyaztaş FY, Can M, Bütün C. Ateşli silah yaralanmalarında hekim sorumluluğu. In: Birinci Basamakta Adli Tıp. Koç S, Can M, editors. 2nd Ed. İstanbul: Istanbul Tabip Odası; 2010. p. 74−80. 7. Karaca MA, Kartal ND, Erbil B, Öztürk E, Kunt MM, Şahin TT, et al. Evaluation of gunshot wounds in the emergency department. Ulus Travma Acil Cerrahi Derg 2015;21:248−55. 8. Saukko P, Knight B. Knight’s forensic pathology. 3rd ed. New York:

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Meral et al. Investigation of firearm injury cases presented to training and research hospital’s emergency service Arnold; 2004. 9. Tintinalli JE, Stapczynski S, Ma OJ, Yealy DM, Meckler GD, Cline DM. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. 8th ed. North Carolina: 2016. 10. Türkoğlu A, Tokdemir M, Tunçez FT, Börk T, Yaprak B, Şen M. Assessment of Autopsied Deaths due to Firearms between 2010-2012 in Elazığ. The Bulletin of Legal Medicine 2012;17:8−14. 11. Tokdemir M, Kafadar H, Türkoğlu A. Evaluation of Fire-Gun injuries in 304 Cases. E-Journal of New World Sciences Academy 2009;4:1−7. 12. Kır MZ, Ketenci HÇ, Başbulut AZ, Özsoy S. Evaluation of FirearmRelated Deaths in Kahramanmaraş. J For Med 2012;26:27−37.

13. Çınar K, Şeçer M, Alagöz F, Ulutaş M, Uçkun ÖM, Yıldırım AE, et al. Outcomes And Demostration of Cranial Firearm Injuries: A Multicenter Retrospective Study. TJTES 2015;21:291−6. 14. Erkol Z, Çolak B, Yaycı N, İnanıcı MA. Firearm fatalities in Kahramanmaraş. J For Med 2011;25:1−10. 15. Turkish Penal Code. http://mevzuat.basbakanlik.gov.tr. Accessed, November 6, 2018. 16. The ATLS Subcommittee, American College of Surgeons’Committee on Trauma, The International ATLS working group. Advanced trauma life support (ATLS®). 9th ed. Chicago: Illinois; J Trauma Acute Care Surg, 2013. p. 1363−6.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Bir eğitim ve araştırma hastanesi acil servisine başvuran ateşli silah yaralanması olgularının incelenmesi Dr. Orhan Meral,1 Dr. Caner Sağlam,2 Dr. Birdal Güllüpınar,2 Dr. Özlem Ezgi Aktürk,2 Dr. Serdar Beden,2 Dr. İsmet Parlak3 Sağlık Bilimleri Üniversitesi İzmir Bozyaka Eğitim ve Araştırma Hastanesi, Adli Tıp Kliniği, İzmir Sağlık Bilimleri Üniversitesi İzmir Bozyaka Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, İzmir 3 Aksaray Üniversitesi Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, Aksaray 1 2

AMAÇ: Ateşli silah yaralanmaları, ciddi morbidite ve mortaliteye neden olan ve acil tıp ve adli tıp ile ilgili kriminal olaylardır. Çalışmamızın amacı, ateşli silah yaralanmaları nedeniyle acil servislere başvuran olguların yara özelliklerini değerlendirmektir. GEREÇ VE YÖNTEM: Sağlık Bilimleri Üniversitesi İzmir Bozyaka Eğitim ve Araştırma Hastanesi Acil Servisi’ne ateşli silah yaralanması nedeniyle başvuran 18 yaş ve üzeri 213 olgu çalışmaya alındı. BULGULAR: İncelenen 213 olgunun 182’si (%85.4) erkekti. Olguların yaşları 18–78 yaş arası değişmekte olup yaş ortalaması 33.2±12.6 olarak bulundu. Yaralanmaların en sık Nisan (n=28, %13.2) ve Mayıs (n=25, %11.6) aylarında meydana geldiği tespit edildi. İki yüz on üç olgunun 194’ünün (%91.1) hastanedeki tedavileri tamamlandıktan sonra taburcu edildiği, 19 olgunun (%8.9) ise tüm girişimlere rağmen öldüğü belirlendi. TARTIŞMA: Çalışmamız Türkiye’deki ateşli silah yaralanma patern ve sonuçları hakkında önemli bir kesit sunmakta, ancak bölgesel veriler içermektedir. Bu konuda ülke genelini kapsayan çok merkezli ve multidisipliner çalışmaların literatüre ciddi katkıda bulunacağı düşünülmektedir. Anahtar sözcükler: Acil servis; ateşli silah yaralanması; morbidite; mortalite. Ulus Travma Acil Cerrahi Derg 2020;26(1):74-79

doi: 10.14744/tjtes.2019.08949

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ORIGIN A L A R T IC L E

Factors affecting mortality in patients with traumatic diaphragmatic injury: An analysis of 92 cases Selçuk Kaya, M.D.,1 Önder Altın, M.D.,1 Yunus Emre Altuntaş, M.D.,1 Attila Özdemir, M.D.,2 Ekin Ezgi Cesur, M.D.,2 Nejdet Bildik, M.D.,1 Hasan Fehmi Küçük, M.D.1 1

Department of General Surgery, University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul-Turkey

Department of Thoracic Surgery, University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: This study aims to investigate the factors associated with mortality in patients with traumatic diaphragmatic rupture (TDR). METHODS: The records of patients who were operated on at a single hospital with the indication of blunt or penetrating thoracoabdominal injuries between January 2010 and June 2018 and who were perioperatively diagnosed with a diaphragmatic injury were evaluated retrospectively. The details of demographic characteristics, the type and localization of the trauma, presence and number of associated organ injuries, vital signs at admission, time from admission until surgery, type of operation, type of diaphragmatic repair, therapeutic approach, complications and Injury Severity Score (ISS) were analyzed. RESULTS: A total of 92 patients were included in this study. The mortality rate throughout the postoperative period was 15.2%. A penetrating injury was detected in 77.2% of the patients. Associated organ injury was most frequently in the liver, which was significant as a factor that increased mortality (p=0.020). The mortality rate was significantly lower among patients who underwent repair of diaphragmatic rupture when compared with untreated patients (p=0.003). Atelectasis was the most common complication. An ISS ≥24 points in patients with TDR was found to be an independent risk factor associated with mortality (p=0.003). CONCLUSION: Other organs are frequently involved in cases of TDR, and mortality increased significantly in cases with associated liver injury. An ISS of ≥24 was determined to be an independent risk factor associated with mortality. Since the main determinant of mortality was the presence or absence of additional organ injuries, it is important that this should be taken into consideration in these patients. Keywords: Blunt and penetrating trauma; diaphragmatic injury; thoracoabdominal injury.

INTRODUCTION Traumatic diaphragmatic rupture (TDR) usually arises from blunt thoracoabdominal trauma (such as traffic accident, falling from a height, crush injury) or penetrating trauma (such as sharp object injuries, gunshot wounds). Rarely, TDR may also occur as a result of childbirth, severe vomiting, severe cough, weight lifting, or iatrogenic injuries.[1,2] Although the incidence of TDR is not fully known due to masking or organ trauma being overlooked in the larger clinical picture, the incidence has been reported as 1% to

7% in cases of blunt trauma, and 10% to 15% in cases of penetrating trauma.[3–5] Diaphragmatic injuries can be insidious and without any symptoms. It is typically not dominant in the clinical picture of trauma patients.[6,7] Some 7% to 66% of patients with a blunt diaphragmatic rupture are not diagnosed at admission and are followed up with conservative treatment.[8] This may be related to associated morbidity and mortality. It has been reported that 7% of the patients with penetrating thoracoabdominal trauma may have diaphragmatic injury.[9] The

Cite this article as: Kaya S, Altın Ö, Altuntaş YE, Özdemir A, Cesur EE, Bildik N, et al. Factors affecting mortality in patients with traumatic diaphragmatic injury: An Analysis of 92 cases. Ulus Travma Acil Cerrahi Derg 2020;26:80-85. Address for correspondence: Selçuk Kaya, M.D. SBÜ Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, İstanbul, Turkey Tel: +90 216 - 458 30 00 E-mail: selcukkaya_36@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):80-85 DOI: 10.14744/tjtes.2019.82930 Submitted: 16.03.2019 Accepted: 24.07.2019 Online: 30.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Kaya et al. Factors affecting mortality in patients with traumatic diaphragmatic injury

increased tendency for conservative treatment of blunt and penetrating abdominal trauma may result in delays in the diagnosis of diaphragmatic injury. However, the use of imaging methods can increase the possibility of diagnosis.

dian and interval and analyzed with the Mann-Whitney U test. Numerical data were analyzed using a chi-square test or Fisher’s exact test, as necessary. The normality of the data was analyzed using the Kolmogorov-Smirnov test.

A multidisciplinary approach saves lives because of the possibility of injury to both intrathoracic and abdominal organs. The preferred first approach in the presence of hemodynamic instability is laparotomy.[10] In patients with penetrating or blunt trauma, the diaphragmatic injury may be associated with other organ injuries.[11,12] It has been reported that onethird of patients underwent laparotomy in the early period due to other organ injuries, and the injury to the diaphragm was noticed and repaired intraoperatively.[13] In the literature, the reported mortality rates related to blunt and penetrating thoracoabdominal injury range from 7.8% to 32.1%.[5,12,14] This study aims to investigate factors associated with mortality in patients with TDR.

RESULTS

MATERIALS AND METHODS This research was a descriptive and analytical retrospective study of the patients who were operated on with the indication of a blunt or penetrating thoracoabdominal injury between January 2010 and June 2018 and were perioperatively diagnosed with a diaphragmatic injury. The present study was approved by the ethics committee of our hospital (2018/514/144/8). The patient information was obtained from the hospital database. Details of the demographic characteristics of the patients, the type of injury (blunt/penetrating), lateralization of the trauma (right, left, bilateral), presence of associated organ injury (liver, spleen, hollow organ, pancreas, kidney), number of additional organ injuries (none, 1, 2, 3), the patient’s blood pressure at the time of admission (normotensive, hypotensive, shock), the timing of surgery (within the first 2 hours, 2-24 hours, more than 24 hours after admission), type of operation (laparotomy, thoracotomy, thoracolaparotomy, laparoscopic exploration), diaphragmatic repair (non-repair, primary repair, repair with mesh), therapeutic approach (transdiaphragmatic aspiration, thoracic drainage) and complications (atelectasis, pneumonia, empyema, bile fistula) were evaluated. An Injury Severity Score (ISS) was calculated for all of the patients. The primary focus of this study was mortality-related factors.

Statistical Analysis IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY, USA) was used to calculate a t-test for age and ISS, as well as a chi-square test for the other variables. Posthoc tests (Bonferroni, Tukey) were performed for comparisons between groups. Normally distributed data were defined by mean±SD (? X±s) and analyzed using t-tests. Data with a non-normal distribution were defined using the meUlus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

A total of 92 patients who underwent surgery for a blunt or penetrating thoracoabdominal injury between January 2010 and June 2018 and had a perioperative diaphragmatic injury detected were included in this study. Of these patients, 81 (88%) of them were male and 11 (12%) of them were female; the overall mean age was 34.98 years (±14.681 years). The mortality rate throughout the postoperative period was 15.2%. A penetrating injury (n=71; 77.2%) was more common than a blunt injury (n=21; 22.8%). However, there was borderline significance for a blunt trauma association with mortality (p=0.052). The localization of the trauma was specified as unrelated to the lesion in three cases (3.3%), to the right of the midline in 26 (28.3%) cases, left of the midline in 54 (58.7%), and bilateral in 9 (9.8%) cases. The mortality rate was significant in patients with left-sided and bilateral injuries (p=0.012). The most frequent organ injury involved the liver (n=35; 29.4%), followed by a hollow organ (n=33; 27.7%) and the spleen (n=30;25.2%). A liver injury was a statistically significant factor that increased mortality (p=0.020). Fifteen (16.3%) patients had isolated diaphragmatic injuries. The mortality rate was significantly higher in patients with a single-organ injury accompanying diaphragmatic injury (n=52; 56.5%). Patients who were hypotensive and in shock at admission had a higher rate of mortality. The mean ISS score was 19.12±6.890 points (range: 9–38 points). The mean ISS score was 18.21 points (±6.350 points) among the patients who survived and 24.21 points (±8.346 points) among the patients who died (p=0.001). Fifteen (19.2%) patients who survived and eight (57.1%) deceased patients had an ISS score of ≥24 (Table 1). An ISS score of ≥24 points in TDR patients was determined to be an independent risk factor associated with mortality (p=0.003) (Table 1). The approach to the diaphragmatic injury applied was primary repair in 81 (88.0%) patients, two (2.2%) patients had a mesh repair, and seven (7.6%) patients did not undergo any repair. Non-repaired patients were either patients undergoing damage control surgery or with small lacerations that were difficult to reach behind the liver dome. Two patients (2.1%) died during the perioperative period and were excluded from the evaluation of diaphragm repair. The mortality rate was significantly lower in patients who underwent diaphragm repair (p=0.003). Drainage with a thoracic tube was performed in 79 (85.9%) patients and transdiaphragmatic pleural aspiration in 11 (12%) patients. The emerging complications observed were atelectasis (n=11; 11.9%), pneumonia (n=5; 5.4%), empyema (n=5; 5.5%) and biliary fistula (n=1; 1%). The pa81

Kaya et al. Factors affecting mortality in patients with traumatic diaphragmatic injury

Table 1. Mortality-related factors in patients with diaphragmatic rupture Age (years), mean±SD

Survived

Exited

Total

34.12±14.265

39.79±16.558

34.98±14.681

0.405

Gender 0.771

Male

69 (88.5)

12 (85.7)

81 (88.0)

Female

9 (11.5)

2 (14.3)

11 (12.0)

Trauma, n (%)

Blunt

15 (19.2)

6 (42.9)

21 (22.8)

Penetrating

63 (80.8)

8 (57.1)

71 (77.2)

Laterality, n (%)

0.052

0.004

No lesion

3 (3.8)

3 (3.3)

–

Right-sided

19 (24.4)

7 (50.0)

26 (28.3)

0.06

Left-sided

51 (65.4)

3 (21.4)

54 (58.7)

0.012

Bilateral

5 (6.4)

4 (28.6)

9 (9.8)

0.012

Diaphragmatic lesion

Right-sided

27 (34.7)

6 (42.8)

33 (35.9)

Left-sided

48 (61.5)

7 (50.0)

55 (59.8)

Bilateral

3 (3.8)

1 (7.1)

4 (4.3)

Associated organ injury, n (%)

None

15 (16.3)

15 (12.6)

0.0358

0.001 –

Liver

25 (27.2)

10 (10.9)

35 (29.4)

0.020

Hollow organ

24 (26.1)

9 (9.8)

33 (27.7)

0.318

Spleen

24 (26.1)

6(6.5)

30 (25.2)

0.339

Vascular

3 (3.3)

3 (2.5)

–

Pancreas

1 (1.1)

2 (1.7)

0.472

Kidney

1 (1.1)

1 (0.8)

–

Additional organ injury, n (%)

None

15 (19.2)

15 (16.3)

0.015 –

48 (61.5)

4 (28.6)

52 (56.5)

10 (2.8)

4 (28.6)

14 (15.2)

0.15

5 (6.4)

6 (42.9)

11 (12.0)

0.201

Injury Severity Score, mean±SD

18.21±6.197

24.21±8.478

19.12±6.890

0.001

Injury Severity Score >24, n (%)

15 (19.2)

8 (57.1)

23 (25.0)

0.003

Blood pressure at admission

Shock

3 (3.8)

4 (28.6)

7 (7.6)

Hypotensive

43 (55.1)

10 (71.4)

53 (57.6)

0.034

Normotensive

32 (41.0)

32 (34.8)

–

SD: Standard deviation.

tient who developed biliary fistula underwent bile duct repair surgery on the sixth postoperative day. Two (2.2%) patients died during surgery, and 12 (15.2%) patients died during the postoperative period (Table 2).

DISCUSSION Diaphragmatic rupture is likely in most penetrating thoracoabdominal injuries.[4,12] However, early diagnosis of pene82

trating diaphragmatic injuries can be quite difficult. Early diagnosis is typically made either during the detection of a large defect and exploration for a herniation or an accompanying organ injury. In patients with a diaphragmatic injury and a small defect, this condition may be missed more frequently and may have dangerous outcomes.[11,15] In these patients, occlusion/ischemia of hollow visceral organs in the long term, generally due to herniation, and respiratory failure/ischemia Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Kaya et al. Factors affecting mortality in patients with traumatic diaphragmatic injury

Table 2. Surgical outcomes of diaphragmatic rupture patients

Survived

Exited

Total

Timing of the surgery

0–2 hours

47 (60.3)

14 (100.0)

61 (66.3)

p 0.015 0

2–24 hours

15 (19.2)

15 (16.3)

–

>24 hours after admission

16 (20.5)

16 (17.4)

–

Type of surgery

Laparotomy

62 (79.5)

13 (92.9)

75 (81.5)

Thoracotomy

1 (1.3)

1 (1.1)

Thoracolaparotomy

6 (7.7)

1 (7.1)

7 (7.6)

Laparascopic surgery

9 (11.5)

9 (9.8)

0.56

Approach to the diaphragmatic rupture* 0.004

Nonrepairable

5 (6.4)

2 (14.3)

7 (7.6)

0.063

Primary repair

71 (91.0)

10 (71.4)

81 (88.0)

0.003

Prosthesis

2 (2.6)

2 (14.3)

2 (2.2)

0.025

Thoracic drainage*

70 (89.7)

9 (64.3)

79 (85.9)

0.001

Transdiaphragmatic aspiration

8 (10.3)

3 (21.4)

11 (12.0)

0.008

Complications 0.065

Atelectasis

7 (46.7)

4 (57.1)

11 (50.0)

Pneumonia

4 (26.7)

1 (14.2)

5 (22.7)

Empyema

3 (20.0)

2 (28.7)

5 (22.7)

Bile fistula

1 (6.6)

1 (4.6)

*2 patients exited during the perioperative period were excluded from the study.

or presentation of the patient with symptoms related to respiratory failure due to pulmonary atelectasis may be diagnostic. Diaphragmatic injury may occur in blunt trauma due to the development of a sudden pressure difference between the thorax and the abdomen or high kinetic energy caused by the trauma.[5] Diaphragmatic injuries are rare, but they may cause diagnostic problems for surgeons. A delay in diagnosis, the presence of additional organ injury, and the severity of injury increase mortality and morbidity rates.[5,12,14] The incidence of TDR is higher in the fourth decade of life, and in young male patients.[16] Penetrating injuries are approximately twice more frequently seen relative to blunt traumas.[17] The median age of our patients was 34.98 years; 88% were male and 77.2% of them had a penetrating injury, which was consistent with the literature. It has been reported that left-sided diaphragmatic injuries are more common than injury to the right side.[16] The liver has a protective effect on the right diaphragm after blunt trauma, while the left diaphragm is congenitally weaker.[16,18] In this study, 59.9% of the diaphragmatic injuries were left-sided. Perioperatively detected TDR was due to penetrating trauma in 77.2% and blunt trauma in 22.8% of the patients in this study. The mortality rate was 15.2%. Although patients with penetrating trauma were predominant, the mortality rate Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

associated with blunt and penetrating trauma was 6.5% and 8.7%, respectively. In the literature, the mortality rate in patients with diaphragmatic injury due to blunt trauma is greater than that of penetrating trauma.[19] The main factor that will determine mortality and morbidity in the early period due to trauma is visceral organ injury. In patients with blunt trauma, spleen, bladder, lung, and large vascular injuries are observed, where as in penetrating traumas, liver, hollow organ, and pancreatic injuries and haemothorax are observed.[12,14] The reported mortality rates due to blunt and penetrating thoracoabdominal injuries have ranged from 7.8% to 32.1%.[5,12,14] In our study, since the patients were more often exposed to penetrating trauma, liver, hollow organ, and spleen injuries were frequent. Mortality was statistically significantly greater in patients with liver injury compared with other organ injuries. The diaphragm is associated with other organ injuries because of its close relationship with intra-abdominal and intrathoracic organs. Therefore, organ injuries are associated with diaphragmatic rupture in 50% to 100% of cases.[20,21] In our study, 85% of our patients had additional organ injuries. The ISS score also increases in parallel with associated organ injuries. There was a significant increase in mortality in patients with an ISS score of ≥24 points. 83

Kaya et al. Factors affecting mortality in patients with traumatic diaphragmatic injury

This finding was consistent with the literature data.[3,14] Although blunt traumas are most often observed in the right half of the body, they are most frequently reported on the left side in penetrating injuries. This is a result of most people being right-handed.[22] There were more left- sided injuries in the present study, likely due to the predominance of penetrating injuries. For the diagnosis of TDR, first, the physician who initially sees a patient should maintain suspicion of diaphragmatic injury in appropriate cases. According to the hemodynamic status of the patient, diagnostic tools and methods, as well as non-invasive methods, such as thorax graphy, contrast-enhanced radiographs, ultrasonography, and computed tomography, and minimally invasive methods, such as laparoscopy and thoracoscopy may be used. In blunt or penetrating thoracoabdominal injuries, surgery may be performed using open or minimally invasive methods or through abdominal, thoracic, or thoracoabdominal approaches, according to the localization of the trauma. Shaw et al.[23] reported that they performed laparoscopic examinations for the diagnosis and treatment of patients with suspect isolated diaphragmatic injury after 24 hours of follow-up. In this study, diaphragm repair was performed via laparoscopy before discharge in nine patients after at least 24 hours of follow-up. Repair of the diaphragmatic rupture is recommended after the establishment of a diagnosis. Non-absorbable suture materials are preferred for repair.[24] Surgical repair is easy at the time of diaphragmatic rupture, and this is the main rationale for the surgical approach. However, relevant animal studies have shown that spontaneous scarring occurs, especially in small and right-sided diaphragmatic injuries.[25] In our study, the mortality rate was higher in patients who underwent diaphragm repair. Mortality is often related to the severity of the trauma, accompanying organ injury, or prolongation of the operation time, rather than the diaphragmatic injury alone. In the literature, atelectasis has been reported as the most common complication after diaphragmatic injuries. Other complications include pneumonia, sepsis, intraabdominal abscess, wound infection, and respiratory failure. [17] In our study, atelectasis, pneumonia, empyema, and biliary fistula were observed most frequently, which was consistent with the literature. In cases of TDR, other organs are frequently affected, and especially in those with liver injury, mortality rates increase significantly. Moreover, the presence of an ISS of ≥24 was determined to be an independent risk factor associated with mortality. Since the main predictive factor for mortality is the presence or absence of additional organ injuries, this finding should not be overlooked. Ethics Committee Approval: Approved by the local ethics committee (2018/514/144/8). 84

Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: S.K., Y.E.A.; Design: S.K., A.Ö.; Supervision: N.B.; Fundings: S.K., Ö.A.; Materials: S.K., E.E.C.; Data: S.K., Ö.A.; Analysis: S.K., Y.E.A.; Literature search: S.K., Y.E.A.; Writing: S.K.; Critical revision: S.K., H.F.K. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Hillenbrand A, Henne-Bruns D, Wurl P. Cough induced rib fracture, rupture of the diaphragm and abdominal herniation. World J Emerg Surg 2006;1:34. 2. Ozgüç H, Garip G, Kirdak T. A case of diaphragmatic rupture after strenuous exercise (swimming) and jump into the sea. Ulus Travma Acil Cerrahi Derg 2009;15:188−90. 3. Küçük HF, Demirhan R, Kurt N, Ozyurt Y, Topaloğlu I, Gülmen M. Traumatic diaphragmatic rupture: analysis of 48 cases. [Article in Turkish]. Ulus Travma Derg 2002;8:94−7. 4. Scharff JR, Naunheim KS. Traumatic diaphragmatic injuries. Thorac Surg Clin 2007;17:81−5. 5. Okada M, Adachi H, Kamesaki M, Mikami M, Ookura Y, Yamakawa J, et al. Traumatic diaphragmatic injury: experience from a tertiary emergency medical center. Gen Thorac Cardiovasc Surg 2012;60:649−54. 6. Shan R, Sabanathan S, Mearns AJ, Choudhury AK. Traumatic rupture of diaphragm. Ann Thorac Surg 1995;60:1444−9. 7. Lee WC, Chen RJ, Fang JF, Wang CC, Chen HY, Chen SC, et al. Rupture of the diaphragm after blunt trauma. Eur J Surg 1994;160:479−83. 8. Desir A, Ghaye B. CT of blunt diaphragmatic rupture. Radiographics 2012;32:477−98. 9. Leppäniemi A, Haapiainen R. Occult diaphragmatic injuries caused by stab wounds. J Trauma 2003;55:646−50. 10. van der Werken C, Lubbers EJ, Goris RJ. Rupture of the diaphragm by blunt trauma as a marker of injury severity. Injury 1983;15:149−52. 11. Demetriades D, Kakoyiannis S, Parekh D, Hatzitheofilou C. Penetrating injuries of the diaphragm. Br J Surg 1988;75:824−6. 12. Fair KA, Gordon NT, Barbosa RR, Rowell SE, Watters JM, Schreiber MA. Traumatic diaphragmatic injury in the American College of Surgeons National Trauma Data Bank: a new examination of a rare diagnosis. Am J Surg 2015;209:864−9. 13. Williams M, Carlin AM, Tyburski JG, Blocksom JM, Harvey EH, Steffes CP, et al. Predictors of mortality in patients with traumatic diaphragmatic rupture and associated thoracic and/or abdominal injuries. Am Surg 2004;70:157−62; discussion 162−3. 14. Cardoso LF, Gonçalves MVC, Machado CJ, Resende V, Fernandes MP, Pastore-Neto M, et al. Retrospective analysis of 103 diaphragmatic injuries in patients operated in a trauma center. [Article in English, Portuguese] Rev Col Bras Cir 2017;44:245−51. 15. Murray JA, Demetriades D, Asensio JA, Cornwell EE 3rd, Velmahos GC, Belzberg H, et al. Occult injuries to the diaphragm: prospective evaluation of laparoscopy in penetrating injuries to the left lower chest. J Am Coll Surg 1998;187:626−30. 16. Al-Refaie RE, Awad E, Mokbel EM. Blunt traumatic diaphragmatic rupture: a retrospective observational study of 46 patients. Interact Cardiovasc Thorac Surg 2009;9:45−9. 17. Asensio JA, Demetriades D, Rodriguez A. Injury to the diafragm. In:

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Kaya et al. Factors affecting mortality in patients with traumatic diaphragmatic injury Mattox KL, Feliciano DV, Moore EE, editors. Trauma. 4th ed. New York: Mc Graw-Hill; 2000. p. 603−32. 18. Dwivedi S, Banode P, Gharde P, Bhatt M, Johrapurkar SR. Treating traumatic injuries of the diaphragm. J Emerg Trauma Shock 2010;3:173−6. 19. Gürleyik G, Gürleyik E, Güran M, Günal Ö, Pehlivan M, Ünalmışer S. Diaphragmatic Injuires. TIJES 1999;4:262−5. 20. Carter YM, Karmy-Jones RC, Stern EJ. Delayed recognition of diaphragmatic rupture in a patient receiving mechanical ventilation. AJR Am J Roentgenol 2001;176:428. 21. Turmak M, Deniz MA, Özmen CA, Aslan A. Evaluation of the multislice computed tomography outcomes in diaphragmatic injuries related

to penetrating and blunt trauma. Clin Imaging 2018;47:65−73. 22. Hammer MM, Raptis DA, Mellnick VM, Bhalla S, Raptis CA. Traumatic injuries of the diaphragm: overview of imaging findings and diagnosis. Abdom Radiol (NY) 2017;42:1020−7. 23. Shaw JM, Navsaria PH, Nicol AJ. Laparoscopy-assisted repair of diaphragmatic injuries. World J Surg 2003;27:671−4. 24. Trindade RF, Costa FA, Silva Pde P, Caminiti GB, Santos CB. Map of homicides by firearms: profile of the victims and the assaults. [Article in Portuguese] Rev Esc Enferm USP 2015;49:748−52. 25. Caiel BA, Scapulatempo Neto C, Souza Júnior AS, Saad Júnior R. Analysis of natural history of the diaphragmatic injury on the right in mice. Rev Col Bras Cir 2015;42:386−92.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Travmatik diyafragma yaralanması olan hastalarda mortalite ile ilişkili faktörler: Doksan iki olgunun analizi Dr. Selçuk Kaya,1 Dr. Önder Altın,1 Dr. Yunus Emre Altuntaş,1 Dr. Attila Özdemir,2 Dr. Ekin Ezgi Cesur,2 Dr. Nejdet Bildik,1 Dr. Hasan Fehmi Küçük1 1 2

Sağlık Bilimleri Üniversitesi Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, İstanbul Sağlık Bilimleri Üniversitesi Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Göğüs Cerrahisi Anabilim Dalı, İstanbul

AMAÇ: Travmatik diyafragma rüptürü (TDR) olan hastalarda mortalite ile ilişkili faktörleri irdelemektir. GEREÇ VE YÖNTEM: Ocak 2010 ile Haziran 2018 tarihleri arasında künt ve penetran torakoabdominal yaralanma nedeniyle ameliyata alınıp peroperatif diyafragma yaralanması tespit edilen hastalar geriye dönük olarak değerlendirildi. Hastaların demografik özellikleri, travmanın tipi, lokalizasyonu, ilişkili organ yaralanması varlığı, ek organ yaralanması sayısı, hastanın geliş anındaki tansiyon durumu, ameliyata alınma zamanı, operasyon şekli, diyafragma onarım şekli, terapötik yaklaşım türü, komlikasyonlar ve Yaralanma Şiddet Skorları (ISS) değerlendirildi. BULGULAR: Çalışmaya 92 hasta alındı. Mortalite oranı %15.2 idi. Yaralanmanın şekli %77.2 penetran travma ile idi. İlişkili organ yaralanması en fazla karaciğer olup mortaliteyi arttırıcı faktör olarak anlamlıydı (p=0.020). Diyafragma tamiri yapılan hastalarda mortalite yapılmayanlara göre anlamlıydı (p=0.003). En sık komplikasyon atelektazi idi. TDR olan hastaların ISS’nin 24 ve üzerinde olması mortalite ile ilşkili bağımsız bir risk faktörü olarak tespit edildi (p=0.003). TARTIŞMA: Travmatik diyafragma rüptürü sıklıkla diğer organlar ile birliktelik gösterip özellikle karaciğer yaralanmasının eşlik ettiği durumlarda mortalite anlamlı derecede artmaktadır. Ayrıca ISS’nin 24 ve üzerinde olması mortalite ile ilşkili bağımsız bir risk faktörü olarak tespit edilmiştir. Mortaliteyi belirleyen asıl sebep ek organ yaralanmaları olduğu için diyafragma yaralanması olan hastalarda bu durum göz ardı edilmemesi kanısındayız. Anahtar sözcükler: Diafragma yaralanması; künt ve penetran travma; torakoabdominal yaralanma. Ulus Travma Acil Cerrahi Derg 2020;26(1):80-85

doi: 10.14744/tjtes.2019.82930

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ORIGIN A L A R T IC L E

Predictive and prognostic value of L-lactate, D-dimer, leukocyte, C-reactive protein and neutrophil/lymphocyte ratio in patients with acute mesenteric ischemia Sabahattin Destek, M.D.,1 Ayşegül Yabacı, M.D.,2 Yağmur Nur Abik, M.D.,1 Vahit Onur Gül, M.D.,3 Kamuran Cumhur Değer, M.D.1 1

Department of General Surgery, Bezmialem Foundation University Faculty of Medicine, İstanbul-Turkey

Department of Statistic, Bezmialem Foundation University Faculty of Medicine, İstanbul-Turkey

Department of General Surgery, Gülhane Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: Acute mesenteric ischemia (AMI) is a disease that causes an ischemia in the intestines due to the obstruction of the mesenteric vessels feeding the intestines, with a mortality rate reaching up to 80%. The overall incidence of AMI is 0.63 per 100,000 people. Early diagnosis and treatment are very important for survival. There is no ideal biomarker that can reflect different types and stages of AMI. This study investigated the predictive and prognostic value of L-lactate, D-dimer, leukocyte, C reactive protein (CRP) and neutrophil/lymphocyte ratio (NLR) in the preoperative period were investigated in patients operated for AMI. METHODS: A total of 44 patients operated for AMI between 2015 and 2019 were evaluated in this study. Demographic, clinical, radiological, laboratory and surgical findings of the patients included in this study were recorded. The patients were divided into groups according to the etiological type of AMI. L-lactate, D-dimer, CRP, leukocyte, and NLR levels of these patients were determined. Statistical analysis was performed according to AMI groups. RESULTS: The mean age of the 44 patients included in this study was 67.7 years and the female to male ratio was 0.76. According to tomography results, 31.8% (n=14) of the patients had mesenteric artery embolism, 29.5% (n=13) had mesenteric artery thrombus, 25% (n=11) had mesenteric vein thrombus and 13.6% (n=6) had non-occlusive mesenteric ischemia. When AMI types were compared, D-dimer and CRP levels were found to be significantly different from other markers. The total length of stay in the hospital was found to be significantly correlated with the L-lactate (p=0.047) and CRP (p=0.045) levels. In the analyses, CRP was determined to be the common biomarker that could be used in the diagnosis of mesenteric ischemia in all AMI types. CONCLUSION: Particularly, the CRP level can be used effectively in the preoperative period to diagnose AMI and to determine its subtype and clinical course. However, L-lactate, D-dimer, leukocyte and NLR are markers that have no predictive value in the diagnosis of all AMI subtypes. Keywords: Acute mesenteric ischemia; C-Reactive protein; D-dimer; L-lactate; Leukocyte; neutrophil/lymphocyte ratio.

INTRODUCTION Acute mesenteric ischemia (AMI) is a rare disease with high mortality rates that result in ischemia/reperfusion injury due to the obstruction, venous congestion, or vasoconstriction of mesenteric vessels feeding the intestines.[1] AMI accounts for

0.09–0.2% of the acute surgical intervention.[2] The incidence increases with the increasing age, reaching 18% in patients older than 65 years of age.[3] The mean age of onset of AMI is 67 years, and its incidence in men and women is the same. [4,5] Typical symptoms include sudden-onset widespread abdominal pain, nausea, vomiting, diarrhea and rectal bleeding.

Cite this article as: Destek S, Yabacı A, Abik YN, Gül VO, Değer KC. Predictive and prognostic value of L-lactate, D-dimer, leukocyte, C-reactive protein and neutrophil/lymphocyte ratio in patients with acute mesenteric ischemia. Ulus Travma Acil Cerrahi Derg 2020;26:86-94. Address for correspondence: Vahit Onur Gül, M.D. Gülhane Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara, Turkey Tel: +90 312 - 304 50 16 E-mail: vonurgul@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):86-94 DOI: 10.14744/tjtes.2019.61580 Submitted: 22.12.2019 Accepted: 25.12.2019 Online: 30.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Destek et al. Predictive and prognostic value of L-lactate, D-dimer, leukocyte, CRP and NLR in patients with AMI

There are four different etiological types of AMI: arterial embolism (EAMI) (50%), arterial thrombosis (TAMI) (25%), non-occlusive mesenteric ischemia (NOMI) due to vasoconstriction of the mesenteric artery (20%), and venous thrombosis (VAMI) (10%).[1,4,5] [1,5]

Despite the improvements in diagnosis and treatment methods, mortality rates have been still ranging 60–80%.[5,6] Following the surgical intervention, the mortality rates may increase to 32.1% in VAMI, 54.1% in EAMI, 72.7% in NOMI and 77.4% in TAMI.[4,7] The reasons for the increase in mortality rates include late hospital admission, late diagnosis, and the presence of coexisting comorbidities, such as atrial fibrillation (AF), heart failure, atherosclerosis, thrombophilic conditions, and shock with the increasing age.[4–6] Emergency intervention is of great importance, and the mortality rates can decrease to 10–20% with the interventions made within the first six hours; however, the mortality rates may reach 79–100% after 24 hours.[8] The key to early diagnosis is increased clinical suspicion and multidetector computed tomography angiography (MDCTA) should be performed as soon as possible.[1,5] For the biochemical diagnosis of AMI, many biomarkers, such as intestinal fatty acid-binding protein (I-FABP), α-glutathione S-transferase (α-GST), citrulline, D-dimer, L and D-lactate, white blood cell (WBC) count, and neutrophil/lymphocyte ratio (NLR) have been evaluated. However, no consensus has been achieved in this regard.[5,8] There have been still studies being carried out to find an ideal biomarker that is able to reflect different types and stages of AMI.[1,5,8] This retrospective study aims to investigate the predictive value of L-lactate, D-dimer, leukocyte, C reactive protein (CRP) and NLR levels in the preoperative period in patients operated for AMI and to find an ideal biomarker.

MATERIALS AND METHODS Study Population and Design This study included a total of 51 patients who underwent surgery for AMI between 2015 and 2019. Ethical approval was obtained from the Bezmialem Foundation University Faculty of Medicine Ethics Committee with the decision no. 10/161 dated 07.05.2019 to conduct this study. Four of these patients were operated and sent to an external intensive care unit (ICU), and their treatment was continued in another center and data of three patients could not be obtained in full. Therefore, they were excluded from the study. A total of 44 patients whose data could be accessed from hospital archives and patient files were included in this study. Age, sex, body mass index (BMI), Charlson Comorbidity Index (CCI), most prevalent cardiovascular disease (CVD) comorbidities, deep vein thrombus, pulmonary embolism, history of embolism and thrombus (e.g. cerebrovascular disease), preUlus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

vious history of abdominal surgery, duration of complaints, days), and the most common complaints were recorded. L-lactate levels were biochemically measured in venous blood gas (0.3–1.3 mmol/L) and D-dimer (0–0.5 µg/mL FEU), amylase (25–125 U/L), lactate dehydrogenase (LDH) (125–220 U/L), CRP (0–5 mg/L), leukocyte (4.6–10.2 103/LL), and NLR (103/ LL) values were measured in blood plasma samples. Then, the mesenteric vessels involved, for example, superior mesenteric artery (SMA), superior mesenteric vein (SMV), inferior mesenteric artery (IMA) and inferior mesenteric vein (IMV) were examined via CTA. The etiological type of AMI (EAMI, TAMI, VAMI, or NOMI) was identified based on pn clinical and CTA findings of the patients. The following parameters were examined: type of surgical intervention (e.g. laparotomy/laparoscopy, small or large bowel resection), small and large bowel with ischemia, anastomosis or stoma status, presence of drain, operation time (hours), second look application after 24 hours, postoperative bleeding, complications (e.g. intraabdominal abscess or wound infection), length of stay in ICU (days), total treatment duration (days), healing and death status. Demographic, clinical and laboratory parameters of the patients were evaluated according to the AMI types.

Statistical Analysis Descriptive statistics for the categorical variables were expressed as frequency and percentage. Descriptive statistics for the numerical variables following normal distribution were expressed as mean ± standard deviation whereas those not following normal distribution were expressed as median (min-max). Shapiro–Wilk test was used to determine whether the data followed a normal distribution. Student’s t-test was used to determine whether there was a significant difference between the mean values of independent data following normal distribution in the presence of two groups, whereas a one-way analysis of variance (ANOVA) test was used in the presence of three or more groups. Pearson chisquare, Fisher Exact, and Fisher Freeman Halton tests were used to determine whether there was a correlation between the categorical variables or whether they were independent of each other. For the evaluation of quantitative variables, the Mann-Whitney U test was used to compare the mean values of two independent groups, which did not follow a normal distribution. Kruskal Wallis-H Test was used to evaluate whether the difference between the mean values of three or more groups was significant in non-normally distributed groups. Dunn and Bonferroni tests were used for post hoc analyses. The correlation between the numerical variables was determined using Spearman’s Correlation Analysis. The receiver operating characteristic (ROC) curve was used to determine the diagnostic value of biochemical markers (NLR, CRP, L-Lactate, and D-dimer) according to the etiological type of AMI. Youden J index was used to determine cut-off 87

Destek et al. Predictive and prognostic value of L-lactate, D-dimer, leukocyte, CRP and NLR in patients with AMI

values in ROC results. All statistical analyses were performed using IBM SPSS Statistics version 22.0 software (IBM Corporation, Armonk, NY, USA). Results were evaluated at a 95% confidence interval and a p-value of <0.05 was considered statistically significant.

isolated SMV involvement, 9% (n=4) of them had SMV and IMV involvement, and 2.3% (n=1) of them had both SMA and SMV involvement, whereas there was no mesenteric vessel obstruction was observed in 11.4% (n=5) of the patients.

RESULTS

The sub-etiological type of AMI was identified through the CTA results of the patients who were operated for AMI. Of the patients, 31.8% (n=14) of them had EAMI, 29.5% (n=13) of them had TAMI, 25% (n=11) had VAMI, and 13.6% (n=6) of them had NOMI. According to these sub-types, patients with the highest mean age and BMI were in the EAMI group. The AMI sub-types were generally more common in male patients. The highest CCI level was found to be in patients with NOMI. Considering the CVD comorbidities, the disease was accompanied by AF in 46.1% of patients with EAMI, whereas it was accompanied by CVD in 50% of the patients with TAMI, 55.5% of the patients with VAMI, and 50% of the patients with NOMI. The rate of embolism and thrombus history was higher in the EAMI group; one-third of the patients had this history. However, there was no statistically significant difference between the demographic characteristics and AMI types (p>0.05) (Table 1).

The age range of 44 patients included in this study was 24–96 years (mean: 67.7 years), and the female to male ratio was 0.76. The BMI was 20.2–47.2 (mean: 28.8) kg/m2. The CCI of the patients ranged from 0 to 9, with a maximum index of 5 (n=11, 25%), and the index was 0 in 6.8% (n=3) of the patients. In general, the most prevalent CVD comorbidity was coronary artery disease (n=18, 47.4%), whereas 13.6% (n=6) of the patients had no CVD comorbidity. Of the patients, 22.7% (n=10) had a history of previous thromboembolism and half of these patients had a history of previous cerebrovascular disease. Of the patients, 27.3% (n=12) had a history of previous abdominal surgery. There were generalized abdominal pain, nausea, and vomiting in 97.7% (n=43), 81% (n=36) and 65.9% (n=29) of the patients. When the time between the onset of complaints and the time of hospital admission was examined, 9% (n=4) of the patients were admitted to the hospital within the first 12 hours, whereas 43% (n=19) between 12–24 hours and 47.7% (n=21) later than 24 hours. The CTA examinations showed that 63.6% (n=28) of the patients had isolated SMA involvement, 13.6% (n=6) had

Comparison of AMI types with auxiliary biochemical tests performed to make a diagnosis and to determine the level of inflammation before surgery showed a significant difference between the patients with AMI concerning D-dimer and CRP results. The highest D-dimer level (3.46±1.8 µg/mL FEU)

Table 1. Demographic characteristics of the patients with acute mesenteric ischemia according to ischemia types Demographic features

Acute mesenteric ischemia types

EAMI

TAMI

VAMI

NOMI

Sex, n (%)

Male

7 (50)

8 (61.5)

6 (54.5)

4 (66.7)

Female

7 (50)

5 (38.5)

5 (45.5)

2 (33.3)

0.903α

Age (year), mean±SD

71.4±12.2 68.7±13.8 60.0±21.0 70.6±14.7 0.312β

Body mass index (kg/m ), mean±SD

29.7±7.1 27.3±4.1 29.6±5.9 29.3±5.2 0.711β

Charlson Comorbidity Index, mean±SD

4.2±1.7

4.0±2.1

3.4±2.7

5.6±1.8

0.276β 0.768α

Cardiovascular disease, n (%)

Atrial fibrillation

6 (46.1)

4 (40)

2 (22.2)

1 (16.6)

Coronary artery disease

5 (38.4)

5 (50)

5 (55.5)

3 (50)

Embolism/thrombus history, n (%)

9 (64.3)

10 (76.9)

9 (81.8)

6 (100)

Yes

5 (35.7)

3 (23.1)

2 (18.2)

0 (0)

0.449α

Previous abdominal surgery, n (%)

12 (85.7)

9 (69.2)

8 (72.7)

3 (50)

Yes

2 (14.3)

4 (30.8)

3 (27.3)

3 (50)

0436α

α Fisher Freeman Halton test; βOne-Way ANOVA test. EAMI: Mesenteric artery embolism; TAMI: Mesenteric artery thrombosis; VAMI: Mesenteric vein thrombosis; NOMI: Non-occlusive mesenteric ischemia; SD: Standard deviation.

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Destek et al. Predictive and prognostic value of L-lactate, D-dimer, leukocyte, CRP and NLR in patients with AMI

was in the EAMI group, whereas the lowest D-dimer level (1.25±0.9 µg/mL FEU) was in the NOMI group. The difference between the groups was statistically significant (p=0.040). The highest CRP level (65.13±103.2 mg/L) was in the EAMI group, whereas the lowest CRP level (17.65±12.9 mg/L) was in the NOMI group. The difference between the groups was statistically significant (p=0.032). However, no statistically significant difference was found between the groups concerning L-lactate, amylase, LDH, Leukocyte and NLR values (p>0.05) (Table 2).

but it was low (1.24±0.99 µg/mL FEU) in small and large intestinal involvement. This difference was statistically significant (p=0.029). The CRP level was high (44.46±75.3 mg/L) in small intestinal involvement whereas it was low (10.50±7.8 mg/L) in the small and large intestinal involvement, and the difference was statistically significant (p=0.018). However, no statistically significant difference was found between the groups concerning L-lactate, amylase, LDH, Leukocyte and NLR values (p>0.05) (Table 3).

As a surgical treatment, diagnostic laparotomy/laparoscopy (n=12, 27.2%), small bowel resection (n=23, 52.2%), and small bowel and colon resection (n=9, 20.4%) were performed. During the operation, 84% (n=37) of the patients were found to have small intestinal ischemia and 16% (n=7) had colon ischemia as well as small intestinal ischemia. There was a significant difference between the site of involvement in AMI and D-dimer and CRP tests. The D-dimer level was high (2.89±2.10 µg/mL FEU) in small intestinal involvement,

Bowel anastomosis was performed in 40.6% (n=13) of the patients undergoing resection and stoma was opened in 59.7% (n=19). The operation time was 39–93 (mean: 66.6) minutes. An intraabdominal silicone drain was placed in 56.8% (n=25) of the patients. The second look was performed in 45.5% (n=20) of the patients. Two patients with early-stage SMA embolism underwent embolectomy. Of the patients, 22.7% (n=10) were taken to the service after the surgery, whereas 77.3% (n=34) of them were taken to the ICU. The patients who were taken

Table 2. Correlation between acute mesenteric ischemia types and biochemical markers Biomarkers evaluated

Acute mesenteric ischemia types

p¥

EAMI

TAMI

VAMI

NOMI

Med. (Min-Max)

3.40 (1.6–5.6)

2.70 (0.9–5.5)

2.20 (1.4–4.6)

2.65 (1.1–3.1)

0.107

D-dimer (0–0.5 µg/mL FEU)

2.90 (1.30–7.10)

2.10 (0.40–5.90)

0.80 (0.40–7.80)

1.30 (0.20–2.70)

0.040*

Amylase (25–125 U/L)

72.50 (22–593)

122 (41–902)

48 (19–464)

144.50 (27–381)

0.079

277.50 (218–832)

267 (175–524)

263 (162–823)

304 (207–545)

0.792

30.29 (16–412)

18.53 (1.1–50)

12.20 (3.8–248.2)

14.50 (4.6–34)

0.032**

Leukocyte (4.6–10.2 103/µL)

19.10 (6.75–42.10)

18.51 (7.51–50.67)

19.28 (11.48–33.46)

13.40 (4.21–25.66)

0.682

Neutrophil/lymphocyte ratio (103/µL)

15.83 (8.75–44.88)

12.19 (4.14–96.20)

14.46 (2.97–23.70)

11.02 (1.49–39.43)

0.142

L-lactate (0.3–1.3 mmol/L)

LDH (125–220 U/L) CRP (0–5 mg/L)

¥ Kruskal Wallis test. *D-dimer post hoc EAMI-NOMI: p=0.005, **CRP post hoc EAMI-TAMI p=0.008, EAMI-VAMI p=0.029. EAMI: Mesenteric artery embolism; TAMI: Mesenteric artery thrombosis; VAMI: Mesenteric vein thrombosis; NOMI: Non-occlusive mesenteric ischemia; Med.: Median; Min: Minimum; Max: Maximum.

Table 3. Correlation between bowel involvement and biochemical markers in acute mesenteric ischemia Biomarkers evaluated

Site of involvement in acute mesenteric ischemia

p∞

Small intestine

Small and large intestine

Med. (Min-Max)

2.90 (0.9–5.5)

1.50 (1.4–5.6)

0.103

2.30 (0.30–7.80)

0.70 (0.20–2.80)

0.029

96 (19–902)

71 (22–464)

0.615

L-lactate (0.3–1.3 mmol/L) D-dimer (0–0.5 µg/mL FEU) Amylase (25–125 U/L) Lactate dehydrogenase (125–220 U/L)

263 (162–832)

330 (223–400)

0.134

C-reactive protein (0–5 mg/L)

23 (1.9–412)

9 (1.1–22)

0.018

Leukocytes (4.6–10.2 103/µL)

18.51 (4.21–50.67)

20 (10.80–42.10)

0.730

14 (1.49–96.20)

15.86 (4.14–44.88)

0.312

Neutrophil/Lymphocyte ratio (103/µL) Mann-Whitney Test. Med.: Median; Min: Minimum; Max: Maximum.

∞

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Destek et al. Predictive and prognostic value of L-lactate, D-dimer, leukocyte, CRP and NLR in patients with AMI

to the ICU stayed there for 1–60 (mean: 8.23) days. The total length of hospital stay of all patients was 1–60 (mean 11.5) days. While 59% (n=26) of the patients undergoing surgery died, 41% (n=18) were discharged with healing.

Lactate, and D-dimer) and the results were evaluated statistically. The comparison was made between the patients with EAMI, the most common type of AMI, and those with TAMI, VAMI, and NOMI, respectively.

There was a significant correlation between D-dimer and L-lactate (p=0.001). No significant correlation was observed between LDH and amylase (p=0.025). The CRP levels were found to have a significant correlation with L-lactate (p=0.0001) and D-dimer (p=0.0001). There was a significant correlation between NLR and leukocyte (p=0.035). The length of stay in the ICU was found to be correlated with LDH (p=0.0001). The total length of stay in the hospital was found to have a significant correlation with L-lactate (p=0.047), CRP (p=0.045), and length of stay in the ICU (p=0.0001) (Table 4).

According to the ROC analysis results, it was concluded that the diagnosis could be made using NLR or CRP biomarkers in EAMI and TAMI (Fig. 1) (p=0.012 and p=0.0013). The NLR of 12.5 103/µL and above and a CRP level of greater than 19.4 mg/L indicates the presence of mesenteric ischemia (Table 5).

In the present study, the comparison was made according to the etiologic AMI groups to determine the diagnostic, predictive cut-off value of the biomarkers studied (CRP, NLR, L-

According to the ROC analysis results, it was concluded that the diagnosis could be made using L-lactate and CRP biomarkers in EAMI and VAMI (Fig. 2) (p=0.0245 and p=0.008). If the L-lactate is greater than 3 mmol/L or CRP is greater than 12.4 mg/L (Table 5), mesenteric ischemia diagnosis is made (Table 5). According to the ROC analysis results, it was concluded that the diagnosis could be made using D-dimer and CRP biomark-

Table 4. Correlation between biochemical markers in acute mesenteric ischemia Parameters L-lactate D-dimer Amylase LDH Leukocytes CRP Neutrophil/ Length of lymphocyte stay in the ratio ICU (days) D-dimer

r .706**

p .000

n 44

Amylase

r –.056

-.009

p .719

.953

n 44

LDH

r .194

.158

.337*

p .207 .307 .025

n 44 44 44

Leukocytes

r .285

p .061 .313 .441 .984

.156

–.119

–.003

n 44 44 44 44

CRP

r .691** .913** –.053 .097 .117

p .000 .000 .734 .531 .448

n 44 44 44 44 44

Neutrophil/lymphocyte ratio

p .504 .851 .950 .485 .035

.091

n 44 44 44 44 44

Day of stay in the ICU

.266 .047

.103

.212

–.029

.191

.010

.247

.108

.319*

.513** .250

.013

p .166 .214 .106 .000 .101

.082 .760

n 44 44 44 44 44

44 44

Total length of stay

.304 –.099 .521**

p .047 .140 .672 .331 .990

.045 .524

.000

n 44 44 44 44 44

44 44

.301* .226 .066 .150 .002

CRP: C-reactive protein; ICU: Intensive care unit; LDH: Lactate dehydrogenase.

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Destek et al. Predictive and prognostic value of L-lactate, D-dimer, leukocyte, CRP and NLR in patients with AMI

Table 5. The use of biochemical markers in the diagnosis of the acute mesenteric ischemia Etiological Biomarkers Cut-off value Sensitivity Specificity AUC groups EAMI &

0.740

≥12.5

69.23

85.71

0.753

0.012

CRP

>19.4

92.86

69.23

0.797

0.0013

L-lactate

90.91

64.29

0.769

0.008

VAMI EAMI &

Comparison of the ROC curves (p)

NLR

TAMI EAMI &

p (area=0.5)

CRP D-dimer

NOMI

CRP

>12.4

63.64 100.00 0.760 0.0245

>1.73

83.33

85.71

0.893

<0.001

0.554 0.188

50.00 100.00 0.780 0.027

AUC: Area under the ROC curve; EAMI: Mesenteric artery embolism; TAMI: Mesenteric artery thrombosis; VAMI: Mesenteric vein thrombosis; NOMI: Non-occlusive mesenteric ischemia.

ers in EAMI and NOMI (Fig. 3) (p<0.001 and p=0.027). If the D-dimer is >1.73 µg/mL FEU or CRP is >9 mg/L, mesenteric ischemia diagnosis is made (Table 5). In the ROC analysis performed according to the etiologic AMI groups, CRP was found to be the common biomarker that can be used in the diagnosis of mesenteric ischemia in all AMI etiology (Table 5).

DISCUSSION Mesenteric ischemia was first described by Antonio Beniviene in the 15th century in a book titled Vascular Disorders of the Intestines that describes every aspect of mesenteric ischemia in detail, which was published in 1971.[9] However, there are still many aspects of mesenteric ischemia that have not been clarified yet.[1,9]

Ten percent of mesenteric ischemia is a chronic type, whereas 90% is an acute type.[10] While 90% of chronic mesenteric ischemia originates from progressive atherosclerotic disease, 75–80% of AMIs arise from embolism or thrombus.[8,10] The superior mesenteric artery is affected in 75–85% of all mesenteric ischemia cases since the angle at which the SMA comes out from the aorta is narrow and the diameter of the lumen is wide, which plays a major role in the development of AMI.[8,11] Irreversible AMI phase begins in cases where systemic blood pressure is below 40 mmHg and 75% reductions in blood flow for more than 12 hours or 100% occlusion for more than six hours.[4,10,11] Mucosa develops in the first stage of necrosis, submucosa and muscularis propria in the second stage and transmural bowel necrosis develops in the third stage.[10] Development of transmural infarction results in perforation, peritonitis, and death.[1,4]

100

60 Sensitivity

Sensitivity

20 NLR CRP 0 0

40 60 Specificity

100

Figure 1. The efficacy of neutrophil/lymphocyte ratio and C-reactive protein in the diagnosis of mesenteric artery embolism and thrombosis.

Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

20 L-lactate CRP 0 0

40 60 Specificity

100

Figure 2. Efficacy of L-lactate and C-reactive protein in the diagnosis of mesenteric artery embolism and mesenteric vein thrombosis.

Destek et al. Predictive and prognostic value of L-lactate, D-dimer, leukocyte, CRP and NLR in patients with AMI

100

Sensitivity

20 NLR CRP 0 0

40 60 Specificity

100

Figure 3. Efficacy of D-dimer and C-reactive protein in the diagnosis of mesenteric artery embolism and non-occlusive mesenteric ischemia.

In Europe and the USA, AMI constitutes 1:1000 of the patients hospitalized with acute abdomen diagnosis in one year.[6,11] The overall incidence of AMI in Europe is 0.63 per 100,000 people.[11] It is seen equally in females and males. [1] However, 70% of the patients have been reported to be females in several studies.[4,6] It is more common in the age of 70.[1,4,11] The disease is accompanied by cardiovascular comorbidities, such as AF, coronary artery disease, and ischemic heart disease, in 80% of the patients.[4,11,12] One-third of the patients have a history of previous embolism/thrombosis.[1,11] The mean age of the patients was 67.7 years in the present study. The rate of male patients was 56.8% and the female to male ratio was 0.76. The mean BMI of the patients included in the present study was 28.8 kg/m2. Cardiovascular comorbidity was present in 86.4% of the patients, whereas 47.4% had coronary artery disease. The rate of patients with a history of thromboembolism was 22.7%. These data were compatible with the relevant literature. We believe that the high incidence rate in male patients in the present study is due to region and the incidence of AMI has been reported to be higher in studies carried out in Turkey.[13,14] The most common etiologic form of AMI (45â&#x20AC;&#x201C;50%) is EAMI with SMA embolism.[6,11] The main risk factors are AF, cardiac arrhythmias, rheumatic valve disease, coronary artery disease, and myocardial infarction.[1,10,11] In EAMI, 33% of patients have a history of embolism.[11] Sudden and severe nonlocalized abdominal pain, vomiting, diarrhea are seen in the beginning. However, there might be generalized abdominal pain, fever, bloody diarrhea and shock if transmural infarction develops.[1,11] Heart diseases, such as AF, gastric-emptying disorder and Bergan Triad presenting with incompatible symp92

toms, may not always occur.[15] Embolism is usually located 6 to 8 cm distal to the origin of the SMA, beyond the middle colic artery outlet and thus, the proximal jejunum and colon are protected.[1,15] If the diagnosis and treatment can be performed within the first 24 hours, the survival rate is 89.4%; however, if the diagnosis is delayed, this rate decreases to 27.1%.[15] Diagnosis is made using CTA.[16] Laboratory findings are insufficient for diagnosis.[15,16] Open embolectomy and laparotomy are performed in its treatment.[15,17] In the present study, 31.8% of the patients had EAMI, the ratio of male patients to female patients was equal and the age at which the disease is seen most was 71.4 years. According to other types, patients with the highest mean age and BMI were in the EAMI group. In EAMI, the disease was accompanied by AF in 46.1% of the patients, whereas 35.7% had a history of embolism/thrombus. TAMI, which is the thrombosis of SMA, accounts for approximately 25% of the AMI cases.[1,4,11] The main risk factors are known to be arteriosclerosis, hypertension, diabetes, hyperlipidemia, and antiphospholipid syndrome.[11] It should be suspected, particularly in patients with atherosclerotic disease, who have a recent history of postprandial pain and weight loss.[1,11] Thrombotic obstructions are located more proximal to embolic obstructions and may lead to jejunum, ileum and colon infarction.[2] In TAMI, the mean age is 70 and the female to male ratio is equal.[12,15] There might be thrombosis in the celiac trunk in 33% of the patients with thrombosis in SMA.[12] If possible, endovascular treatment should be the first choice for the treatment of TAMI.[11] In the present study, 61.5% of the patients with TAMI were male and the mean age was 68.7 years. There was a history of coronary artery disease in 50% of the patients, whereas 23.1% had a history of thrombus. Non-occlusive mesenteric ischemia accounts for 20% of the AMIs.[4] The main risk factors include ischemic heart failure, low flow states (shock, hypovolemia, hypotension), drugs (digitalis, diuretics, beta-blockers, alpha-adrenergic drugs), major abdominal surgery and enteral nutrition. Low cardiac output reduces splanchnic blood flow, causing vasoconstriction of SMA. It occurs when the blood flow decreases below 50% for more than 30 minutes.[1,18] The mean age of patients with NOMI is 76.4 years and 53.8% of the patients are female. [18] Acute and insidious abdominal pain, abdominal distention and blood in the stool can be seen.[11] Progression of the disease to intestinal necrosis leads to an elevation in inflammation markers, such as leukocytes and lactate.[19] Emergency laparotomy should be performed to determine portal venous gas or pneumatosis intestinalis, which are specific radiological symptoms.[19] Although there are no radiological findings, endoscopy and/or laparotomy should be performed if there is high clinical suspicion.[19] Mortality rates reach up to 80% due to advanced age and difficulties in the early diagnosis.[7,19] In the present study, 20% of the patients had EAMI, the ratio of male patients was 66.7% and the age at which the disease is seen most was 70.6 years. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Destek et al. Predictive and prognostic value of L-lactate, D-dimer, leukocyte, CRP and NLR in patients with AMI

Mesenteric vein thrombosis accounts for 10% of AMIs. The mean age of patients at presentation is 45–60 years with a slight male to female predominance.[10,20] Although approximately 21–49% of the patients are idiopathic, the main risk factors are hereditary thrombophilic diseases (e.g. Factor V Leiden, prothrombin mutation, protein S deficiency, and protein C deficiency), malignancies, cirrhosis, acute pancreatitis, and oral contraceptives.[10,11,20] Previous deep venous thrombosis or pulmonary embolism is reported in 50% of the patients.[11] In general, severe bowel ischemia does not occur due to the large collateral network. However, severe hemorrhagic infarction may occur in the intestinal wall.[10] Laboratory tests are not helpful in diagnosis.[20] Diagnosis is made using CTA.[11,20] In VAMI, subacute abdominal pain, bloating, abdominal distention, fever, and occult blood in the stool, which may be lasting for up to two weeks, may occur.[10,11] The first treatment approach for VAMI is anticoagulation and no surgery is required in general.[11,20] In the present study, 54.5% of the patients with VAMI were male and the mean age was 60 years. There was a history of coronary artery disease in 55.5% of the patients, whereas 18.2% of the patients had a history of thrombus. At present, there is no specific laboratory test that can be routinely used for early detection of AMI.[11,21] Computed tomography angiography is used for the definitive diagnosis of AMI.[1,10,11] However, CTA has less specificity in NOMI. Furthermore, CTA is contraindicated in patients with renal dysfunction or contrast allergy.[21] Thus, there is a need for an ideal biomarker that can be used in the diagnosis of AMI. [5,21] The most useful biomarker for early diagnosis should be specific to intestinal ischemia and should be very sensitive to show mucosal ischemia.[11] On the other hand, these biomarkers should be able to indicate the success of the intervention and prognosis.[21] The most common laboratory abnormalities in AMI are hemoconcentration, leukocytosis, high anion gap, high lactate-induced metabolic acidosis, high serum amylase, aspartate aminotransferase, LDH, and creatine phosphokinase levels. None of these are sensitive or specific enough to diagnose AMI.[1,5,11] The large meta-analysis studies on biomarkers studied to date have shown that leukocyte count, L-lactate, LDH, excess base, D-lactate and amylase values cannot distinguish intestinal ischemia. Therefore, they have not been accepted as the ideal biomarkers.[1,5,22] However, it has been shown that plasma I-FABP and α-GST secreted from enterocytes increase in the early stage and might be, therefore, considered as a good biomarker.[5,11,21,22] On the other hand, Ddimer values have been reported to be correlated well with the sequela of intestinal ischemia but have low specificity. [5,21] There are studies in the literature reporting that procalcitonin, ischemia-modified albumin (ET-1), endothelin-1, citrulline, smooth muscle-specific protein (SM-22), cobaltalbumin binding assay (CABA), microRNA-21 (miR-21) and NLR markers can be used in the diagnosis of AMI.[5,14,21,22] DUlus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

dimer, α-GST, and I-FABP are potential plasma biomarkers showing intestinal ischemia and they reflect the activation of intravascular coagulation and intestinal mucosal damage, respectively.[22] In the present study, a statistically significant difference was found in CRP and D-dimer tests concerning AMI type. The CRP and D-dimer levels were highest in the EAMI group and lowest in the NOMI group. This difference was more significant in CRP. However, L-lactate, amylase, LDH, leukocyte, and NLR values have been found to have no diagnostic value. There was a statistically significant correlation between CRP and L-lactate values and length of stay, which was more significant in CRP. In the ROC analysis, CRP was found to be the common biomarker that could be used for diagnosis in all etiological types of AMI. In this study, it has been concluded that L-lactate, D-dimer, leukocyte, and NLR values could not be used for diagnostic purposes in the etiological types of AMI.

Conclusion Despite the improvement in the resolution of CT images, as well as vascular and endovascular intestinal revascularization, the mortality rates in AMI have not changed in the last decade and have remained between 60–80%. Existing clinical, radiological and laboratory tests are not sufficient for the diagnosis of early and reversible mesenteric ischemia. There is a need for easy-to-apply, inexpensive and practical biomarkers that can be measured everywhere. As shown in the present study, CRP is an easily accessible, inexpensive, effective and valuable biomarker that can be used in the diagnosis of various subtypes of AMI. However, further studies are needed to determine threshold values, accuracy standards, and specific biomarkers for different etiologic forms of AMI. Ethics Committee Approval: Approved by the local ethics committee (date: 07.05.2019, no: 10/161). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: S.D.; Design: A.Y., Y.N.A.; Supervision: A.Y.; Materials: S.D.; Data: S.D.; Analysis: A.Y.; Literature search: V.O.G.; Writing: S.D., V.O.G.; Critical revision: K.C.D. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

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Destek et al. Predictive and prognostic value of L-lactate, D-dimer, leukocyte, CRP and NLR in patients with AMI 3. Yasuhara H. Acute mesenteric ischemia: the challenge of gastroenterology. Surg Today 2005;35:185−95. 4. Cudnik MT, Darbha S, Jones J, Macedo J, Stockton SW, Hiestand BC. The diagnosis of acute mesenteric ischemia: A systematic review and meta-analysis. Acad Emerg Med 2013;20:1087−100. 5. Memet O, Zhang L, Shen J. Serological biomarkers for acute mesenteric ischemia. Ann Transl Med 2019;7:394. 6. Clair DG, Beach JM. Mesenteric Ischemia. N Engl J Med 2016;374:959−68. 7. Schoots IG, Koffeman GI, Legemate DA, Levi M, van Gulik TM. Systematic review of survival after acute mesenteric ischaemia according to disease aetiology. Br J Surg 2004;91:17−27. 8. Luther B, Mamopoulos A, Lehmann C, Klar E. The Ongoing Challenge of Acute Mesenteric Ischemia. Visc Med 2018;34:217−23. 9. Boley SJ, Brandt L J, Sammartano R J. History of mesenteric ischemia. The evolution of a diagnosis and management. Surg Clin North Am 1997;77:275−88. 10. Florim S, Almeida A, Rocha D, Portugal P. Acute mesenteric ischaemia: a pictorial review. Insights Imaging 2018;9:673−82. 11. Tilsed JV, Casamassima A, Kurihara H, Mariani D, Martinez I, Pereira J, et al. ESTES guidelines: acute mesenteric ischaemia. Eur J Trauma Emerg Surg 2016;42:253−70.

Travma Acil Cerrahi Derg 2016;22:344−9. 14. Aktimur R, Cetinkunar S, Yildirim K, Aktimur SH, Ugurlucan M, Ozlem N. Neutrophil-to-lymphocyte ratio as a diagnostic biomarker for the diagnosis of acute mesenteric ischemia. Eur J Trauma Emerg Surg 2016;42:363−8. 15. Liao G, Chen S, Cao H, Wang W, Gao Q. Review: Acute superior mesenteric artery embolism: A vascular emergency cannot be ignored by physicians. Medicine (Baltimore) 2019;98:e14446. 16. Wyers MC. Acute mesenteric ischemia: diagnostic approach and surgical treatment. Semin Vasc Surg 2010;23:9−20. 17. Savlania A, Tripathi RK. Acute mesenteric ischemia: current multidisciplinary approach. J Cardiovasc Surg (Torino) 2017;58:339–50. 18. Pérez-García C, de Miguel Campos E, Fernández Gonzalo A, Malfaz C, Martín Pinacho JJ, Fernández Álvarez C, et al. Non-occlusive mesenteric ischaemia: CT findings, clinical outcomes and assessment of the diameter of the superior mesenteric artery. Br J Radiol 2018;91:20170492. 19. Bourcier S, Oudjit A, Goudard G, Charpentier J, Leblanc S, Coriat R, et al. Diagnosis of non-occlusive acute mesenteric ischemia in the intensive care unit. Ann Intensive Care 2016;6:112. 20. Hmoud B, Singal AK, Kamath PS. Mesenteric venous thrombosis. J Clin Exp Hepatol 2014;4:257−63.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut mezenterik iskemi hastalarında L-laktat, D-dimer, lökosit, CRP ve nötrofil/lenfosit oranının prediktif ve prognostik değeri Dr. Sabahattin Destek,1 Dr. Aysegül Yabacı,2 Dr. Yağmur Nur Abik,1 Dr. Vahit Onur Gül,3 Dr. Kamuran Cumhur Değer1 Bezmialem Vakıf Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul Bezmialem Vakıf Üniversitesi Tıp Fakültesi, İstatistik Anabilim Dalı, İstanbul 3 Gülhane Eğitim Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara 1 2

AMAÇ: Akut mezenterik iskemi (AMİ) bağırsakları besleyen mezenterik damarların obstrüksiyonuyla bağırsaklarda iskemiye neden olan, mortalite oranı %80’i bulan hastalık grubudur. İnsidansı 100.000’de kişi başına 0.63’tür. Sağkalım için erken tanı ve tedavi çok önemlidir. AMİ’nin farklı tip ve aşamalarını yansıtabilen ideal bir biobelirteç yoktur. Çalışmamızda AMİ tanısıyla ameliyat edilen hastalarda ameliyat öncesi aşamada L-laktat, D-dimer, lökosit, C-reaktif protein (CRP) ve nötrofil/lenfosit oranının (NLO) prediktif ve prognostik önemi araştırıldı. GEREÇ VE YÖNTEM: Bu çalışmada 2015–2019 tarihleri arasında AMİ tanısı ile ameliyat edilen 44 hasta incelendi. Çalışmaya alınan hastaların demografik, klinik, radyolojik, laboratuvar, cerrahi bulguları dahil edildi. Hastalar etiyolojik olarak AMİ grubuna göre gruplandırıldı. Bu hastaların L-laktat, D-dimer, CRP, lökosit, NLO seviyeleri belirlendi. AMİ gruplarına göre istatiksel analiz yapıldı. BULGULAR: Çalışmaya alınan 44 hastanın yaş ortalaması 67.7 yıl, kadın erkek oranı 0.76 idi. Tomografi bulgularına göre hastaların %31.8’inde (n=14) mezenter arter embolisi, %29.5’inde (n=13) mezenter arter trombüsü, %25 (n=11) hastada mezenter ven trombüsü, %13.6’sında (n=6) non-oklüsiv mezenter iskemi saptandı. AMİ tipleriyle karşılaştırıldığında D-dimer ve CRP testleri diğer markırlara göre anlamlı şekilde farklı bulundu. Toplam yatış süresi ile L-laktat (p=0.047) ve CRP (p=0.045) ile anlamlı bir korelasyon saptandı. Yapılan analizlerde tüm AMİ tiplerinde mezenter iskemi tanısında kullanılabilecek ortak biyobelirteç CRP olmuştur. TARTIŞMA: Ameliyat öncesi özellikle CRP düzeyinin AMİ tanısında, alt tipini belirlemede ve klinik seyrini belirlemede etkin şekilde kullanılabilir. Ancak L-laktat, D-dimer, lökosit ve nötrofil/lenfosit oranlarının tüm AMİ alt tiplerinin tanısını koymada etkinliği yoktur. Anahtar sözcükler: Akut mezenter iskemi; CRP; D-dimer; L-laktat; lökosit; nötrofil/lenfosit oranı. Ulus Travma Acil Cerrahi Derg 2020;26(1):86-94

doi: 10.14744/tjtes.2019.61580

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ORIGIN A L A R T IC L E

Traumatic upper extremity injuries: Analysis of correlation of mangled extremity severity score and disabilities of the arm, shoulder and hand score Gloria Maria Hohenberger, M.D.,1 Janos Cambiaso-Daniel, M.D.,2 Angelika Maria Schwarz, M.D.,3 Stafanos Boukovalas, M.D.,4 Franz Josef Seibert, M.D.,1 Peter Konstantiniuk, M.D.,5 Tina Cohnert, M.D.5 1

Department of Orthopaedics and Trauma, Medical University of Graz, Graz-Austria

Division of Plastic, Reconstructive and Aesthetic Surgery, Department of Surgery, Medical University of Graz, Graz-Austria

AUVA Trauma Hospital Styria/Graz, Graz-Austria

Department of Plastic Surgery, University of Texas Medical Branch, Galveston, Texas-USA

Division of Vascular Surgery, Department of Surgery, Medical University of Graz, Graz-Austria

ABSTRACT BACKGROUND: The Mangled Extremity Severity Score is a decision-making tool for limb amputation after trauma. The Disabilities of the Arm, Shoulder and Hand questionnaire was developed to quantify posttraumatic functional deficits of the upper extremity. This study aims to determine the correlation between these two assessments. METHODS: In this study, a retrospective review of all patients with upper extremity injuries who had been treated with vascular reconstruction at two centres between 2005 and 2014 was performed. The respective Mangled Extremity Severity Score was calculated for each participant. Patients were recalled for follow-up examination and assessment of the Disabilities of the Arm, Shoulder and Hand Score. RESULTS: In this study, 14 patients met the inclusion criteria. The mean total Mangled Extremity Severity Score was 5.9 and the mean total Disabilities of the Arm, Shoulder and Hand Score was 30 points. There was no statistically significant correlation between these assessments (Spearmanâ&#x20AC;&#x2122;s rank correlation coefficient: 0.49, p=0.075). CONCLUSION: The Disabilities of the Arm, Shoulder and Hand Score did not correlate significantly with the Mangled Extremity Severity Score. Keywords: Amputation; mangled extremity; upper extremity trauma; vascular trauma.

INTRODUCTION Mangled upper extremities represent challenging injuries demanding rapid diagnostics and intervention to reach limb salvage with satisfactory functional results. Experience gained from combat settings in recent decades has highly improved the management of these devastating injuries, with a reported

decrease of amputation rates from 72% to fewer than 10%. [1] Furthermore, mangled extremities often occur in patients with multiple severe injuries, often involving the head, chest and abdomen, requiring coordinated care and sometimes surgical interventions from multiple teams. Although early management of mangled limbs is critical to maximise the chances of successful extremity salvage and optimise the functional

Cite this article as: Hohenberger GM, Cambiaso-Daniel J, Schwarz AM, Boukovalas S, Seibert FJ, Konstantiniuk P, et al. Traumatic upper extremity injuries: Analysis of correlation of mangled extremity severity score and disabilities of the arm, shoulder and hand score. Ulus Travma Acil Cerrahi Derg 2020;26:95-102. Address for correspondence: Gloria Maria Hohenberger, M.D. Department of Orthopaedics and Trauma Surgery, Medical University of Graz, Graz, Austria Tel: +436508885049 E-mail: hohenberger.gloria@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):95-102 DOI: 10.14744/tjtes.2019.44939 Submitted: 22.08.2018 Accepted: 11.03.2019 Online: 30.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Hohenberger et al. Traumatic upper extremity injuries

outcome, treatment of other life-threatening injuries take priority, following the established Advanced Trauma Life Support protocol. In these cases, definitive treatment of the limb injuries may be performed in a delayed fashion. The indications for limb amputation and the optimal timing of definitive surgical intervention remain controversial, and review of larger series of patients would be valuable.[2,3]

to this study. Regarding this Disabilities of the Arm, Shoulder and Hand Score, the standard version (total Disabilities of the Arm, Shoulder and Hand Score) consists of 30 questions and ranges from 0 to 100 points. Further, two optional modules (Sports/Performing Arts Module & Work Module) each, including four questions, can be assessed. Generally, higher values represent worse outcomes.

Johansen et al.[4] described the Mangled Extremity Severity Score as an objective prediction tool for limb salvage. This assessment was primarily designed for severe lower extremity traumas and later expanded for upper extremity injuries. [3] Since then, it has been utilised by various authors for both upper and lower limbs.[1,2,5,6] For postoperative evaluation, the Disabilities of the Arm, Shoulder and Hand questionnaire,[7] postulated by the American Academy of Orthopedic Surgeons, forms a convenient tool for self-assessment of upper extremity disability and symptoms. It can detect even small functional deficits after upper limb injuries. However, to our knowledge, the correlation between the Mangled Extremity Severity Score scoring system and the Disabilities of the Arm, Shoulder and Hand Score has not been examined in the current literature.

Statistical Analysis

This study aims to assess whether or not the Mangled Extremity Severity Score can accurately predict the postoperative function of the mangled limb using the Disabilities of the Arm, Shoulder and Hand Score as an objective assessment tool. The second goal in this study was to evaluate if the defined Mangled Extremity Severity Score threshold for amputation (≥7 points) was applicable in our patient group.

MATERIALS AND METHODS Data Collection Retrospective data analysis included all patients with upper extremity traumas who had been treated surgically, including vascular reconstruction at our level-I trauma centre and an affiliated level-III trauma centre between January 2005 and December 2014. Only patients with non-iatrogenic vascular injuries limited to vessels proximal to the wrist joint were included in our analysis. Patients with traumatic or primary amputation were excluded from this study. This study was approved by the local ethics committee (EC number: 1298/2015). Collected data included gender, age, injury pattern (blunt or penetrating), concomitant injuries (upper extremity fractures, nerve or muscular lesions), as well as surgical interventions. Further, the Mangled Extremity Severity Score was calculated for each patient using data collected from the medical records. All included eligible patients were then contacted and were requested to complete the Disabilities of the Arm, Shoulder and Hand Score (see supplementary material). Informed consent was signed by all participants who agreed to contribute 96

All calculations were performed using the Statistical Package for Social Sciences (SPSS) 21.0 (SPSS Inc., Chicago, USA). Continuous variables were presented as mean and standard deviation (SD), median, minimum and maximum, categorical data as frequencies and percentages. Since the data for the Mangled Extremity Severity Score and the Disabilities of the Arm, Shoulder and Hand Score did not reveal standard distribution, Spearman’s rank correlation coefficient was used for analysis. A p-value below 0.05 was considered statistically significant.

RESULTS From January 2005 to December 2014, 14.981 open or endovascular interventions were performed at our level-I trauma centre by the Division of Vascular Surgery. During this time interval, six patients sustained traumatic upper extremity amputation. Patient search through the digital hospital archiving systems identified 39 patients who had sustained upper extremity traumas, including vascular injuries and subsequent reconstruction. The respective records were assessed for accuracy and completeness. Among all patients included, fourteen signed informed consent for participation in this study and underwent follow-up examination in 2015 for calculation of their Disabilities of the Arm, Shoulder and Hand Score. Among these, thirteen patients had been treated at the level-I centre and one patient had undergone surgery at the level-III trauma centre. Regarding the rest of 25 patients who were not included in this study, seven had died before this study, three patients rejected participation, eleven patients did not respond to the written invitation, two patients were lost in follow-up, and two patients had no available contact information. The mean follow-up time was 70.1 months (SD 35.8; range: 17–124). The sample consisted of solely male participants, with a mean age of 34.4 years (SD 15.8; range 16–67) at the time of trauma. Nine cases (64%) affected right and five (36%) left extremities, whereas nine injuries concerned the dominant and five traumas the non-dominant side. Regarding the anatomic location of vascular injuries, the brachial artery was found to be the most commonly affected vessel (nine cases/64%), followed by the subclavian artery (three cases/21%). In one case, only the radial artery was involved, and in one case both the radial and ulnar arteries Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Clavicle

Clavicle plating

None

N.A.

Brachial artery Direct arterial suture N.A.

Radial & ulnar

Venous bypass

None

Median & ulnar nerves

None

Venous bypass Median & ulnar nerves &

Radial artery Direct arterial suture Cephalic vein Direct suture

None

of the brachial plexus

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arm fixator

External fixator

Brachial artery

artery

Subclavian

artery

Subclavian

Venous bypass

Direct arterial suture

Venous bypass

None

Yes

N.A.

External fixator

N.A.

Brachial artery

Brachial artery Venous bypass

Venous bypass

Balloon dilatation

Brachial artery Venous patch plasty

Closed reduction Brachial artery Direct arterial suture

None

Cubital vein

None

brachial vein

Medial

None

Median nerve

None

Radial nerve

None

Brachial plexus

N.A.

Median nerve & anterior

Direct suture Radial & median nerves

Direct suture

N.A.

Venous bypass

N.A.

Nervous

Suture

N.A.

None

N.A.

None

Suture

N.A.

anastomosis

End-to-side-

N.A.: Means not applicable.

interosseous nerves interposition

None

humerus

Distal

humeral shaft

scapula,

external upper

(for approach)

Clavicle plating,

Clavicle plating

Clavicle,

Closed reduction Brachial artery

Scapula

Yes

None

of the radial nerve

N.A.

Venous bypass

Ligation

Closed reduction Brachial artery

cubital vein

Median

Median & inferior truncs

superficial branch

None

N.A.

arteries

None

Yes

None

artery

Venous patch plasty

Subclavian

Yes

None

Yes

None

Yes

N.A.

Yes

N.A.

Location Dislocation Bony Injured Vascular Injured Intervention Injured nerve(s) Neural Injured Muscular reconstruction muscles/ reconstruction of and joint artery reconstruction veins 2nd injured fracture(s) intervention vessel tendons

Patient

Table 1. Details of the respective injury and treatment characteristics, the patient sequence is chronological

Hohenberger et al. Traumatic upper extremity injuries

were injured (Table 1). Seventy-one percent among all injuries were blunt and 29% penetrating. Techniques for vascular reconstruction involved venous interposition or bypass (seven patients/50%), arterial suture (three patients/21%), venous patch plasty (two patients/14%) as well as thrombectomy (one patient/7%) and arteriotomy with balloon dilatation (one patient/7%). All of these were conducted by a vascular surgeon or by an experienced trauma surgeon with the assistance of a vascular surgeon. Concomitant trauma to more than one vessel occurred in five cases (36%). Regarding associated bone injuries, two patients (14%) sustained at least one closed fracture, and another two (14%) suffered from at least one open fracture. Among these injuries, two clavicle fractures required primary open reduction and internal fixation (ORIF); one supracondylar humeral fracture necessitated primary external fixation and secondary ORIF, one humeral shaft fracture was treated via external fixation and finally, two scapular fractures were managed conservatively. Additionally, four patients suffered dislocation of the elbow, among which one required external fixation, while the rest of the patients were treated with an elbow splint (Table 1). Furthermore, nine patients (64%) were diagnosed with associated nerve injury, out of which five underwent surgical intervention. Six patients (43%) sustained extensive soft tissue injuries involving muscle and/or tendon, which were all treated operatively (Table 1). No major limb amputation was performed in our patient cohort. Five fasciotomies, either prophylactic (4 cases) or due to manifestation of compartment syndrome symptoms (1 patient), were performed.

The mean Mangled Extremity Severity Score was 5.9 (SD 2.4; range: 2–11). Regarding the Disabilities of the Arm, Shoulder and Hand Score, the mean score was 30 points (SD 29.6) with a range from 0 to 94.2 (Table 2). Spearman’s rank correlation coefficient revealed no statistically significant correlation between the total Mangled Extremity Severity Score and the total Disabilities of the Arm, Shoulder and Hand Score (Spearman’s rank correlation coefficient: 0.49, p=0.075) (Table 3). Seven cases (50%) had prolonged ischemia time (>6 hours between injury and successful revascularization). For this subset of patients, the mean Mangled Extremity Severity Score was 6.9, and the Disabilities of the Arm, Shoulder and Hand Score was 43.7 points (SD 35.5; range 0–94.2). Spearman’s rank correlation coefficient was 0.86, which was statistically significant (p=0.013). Additionally, patients with concomitant nerve injury were found to have significantly higher Disabilities of the Arm, Shoulder and Hand Scores in comparison to the group without nerve injury (43.1 vs. 6.5 points, p=0.02). Assessment of the Sports/Performing Arts Module of the Disabilities of the Arm, Shoulder and Hand Score identified twelve patients out of fourteen that had resumed arts or sports after recovering from their injuries. The mean Disabilities of the Arm, Shoulder and Hand Score in this subgroup of patients was 39.1 (SD 38.2; range: 0–100). When the Disabilities of the Arm, Shoulder and Hand Scores were compared to the respective Mangled Extremity Severity Score, a statistically significant correlation was observed with a correlation coefficient of 0.74 (p=0.006) (Table 3).

Table 2. Schedule of Mangled Extremity Severity Score (MESS) and Disabilities of the Arm, Shoulder and Hand Score (DASH) details for each patient Patient Skeletal Limb Shock Age Total DASH DASH DASH and soft ischemia MESS Score Work Sports/Performing tissue injury Module Arts Module 1 2 4*

0 0 6 62.5 0

0 1 2 6.7 0

0 2 6 0.8 N.A.

2 2 8 20.8 N.A.

56.3

1 0 4 39.2 0

6 2 2*

1 0 5 6.7 0

43.8

7 2 6*

2 1 11 94.2 N.A.

8 2 6*

2 0 10 75 43.8

100

9 4 2*

0 0 6 24.2 0

81.3

10 2 2*

0 1 5 0 0

0 1 5 27.5 31.3

N.A.

0 0 3 0.8 0

13 1 4

0 0 5 43.3 25

N.A.

0 1 7 18.3 56.3

37.5

*Means duplication of points due to ischemia >6 hours; N.A.: Means not applicable. The patient sequence is chronological and equal to Table 1.

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Hohenberger et al. Traumatic upper extremity injuries

Table 3. Correlation between Mangled Extremity Severity Score (MESS) and Disabilities of the Arm, Shoulder and Hand Score (DASH) n

Mean MESS (95% CI)

Mean DASH (95% CI)

Spearman’s rank correlation coefficient

Total scores

5.9 (4.5–7.4)

30 (12.9–47.1)

0.49

0.075

Cases with prolonged ischemia time

6.9 (4.5–9.2)

43.7 (10.9–76.5)

0.86

0.013

Cases with applicable Sports/Performing Arts DASH

6.1 (4.4–7.8)

39.1 (14.8–63.3)

0.74

0.0006

Cases with applicable Work DASH

5.3 (3.9–6.7)

14.2 (0.02–28.4)

0.58

0.063

The Disabilities of the Arm, Shoulder and Hand Score Work Module was used to assess the ability of patients to maintain their occupation and could be analysed for eleven patients. Two patients were disabled, either to partial or full capacity, and were unable to work, and one had retired by the time this study was conducted. The mean Disabilities of the Arm, Shoulder and Hand Score value in the subset of patients that returned to work was 14.2 (SD 20.2; range: 0–56.3) and did not correlate significantly with the respective Mangled Extremity Severity Score analysis (correlation coefficient: 0.57; p=0.063) (Table 3). A total of four cases had a Mangled Extremity Severity Score of at least seven points (Table 2). Patient number 14 had a total Mangled Extremity Severity Score of 7 points. His postoperative Disabilities of the Arm, Shoulder and Hand Score was 18.3 points and the patient remained employed at the same position as before his injury. Patient number 4 had a Mangled Extremity Severity Score of 8. His postoperative total Disabilities of the Arm, Shoulder and Hand Score was 20.8 points, while the Sports Module Disabilities of the Arm, Shoulder and Hand Score was 56.3 points. The patient became disabled, whereby he had been partially employed before the trauma. Patient number 8 sustained significant brachial plexus injury, leading to combined sensorimotor deficits. His Mangled Extremity Severity Score was 10 points and his postoperative total Disabilities of the Arm, Shoulder and Hand Score was 75. Despite the dysfunction of the upper extremity, the patient showed very good compensation and was even able to switch his desk job with an assignment to a construction site. Patient number 7 had a Mangled Extremity Severity Score of 11. He had sustained a burst fracture of the 12th thoracic vertebra, leading to spinal canal stenosis and paraplegia, and a complete avulsion of the brachial plexus resulting in motor dysfunction of the upper extremity. His total Disabilities of the Arm, Shoulder and Hand Score and the Disabilities of the Arm, Shoulder and Hand Score Sports Module scores were 94.2 and 75 points respectively, and he was permanently disabled due to his injuries.

DISCUSSION In our patient group, the correlation between the Mangled Extremity Severity Score (mean 5.9 points) and Disabilities of the Arm, Shoulder and Hand Score (mean 30 points) not Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

reveal statistically significant results (p=0.075). This was also observed for the eleven patients with completed Disabilities of the Arm, Shoulder and Hand Score Work Module (p=0.063). For the seven patients with ischemia time exceeding 6 hours, the Mangled Extremity Severity Score (mean 6.85 points) and the Disabilities of the Arm, Shoulder and Hand Score (mean 43.7 points) correlated significantly (p=0.013). Regarding the twelve patients who completed the Disabilities of the Arm, Shoulder and Hand Score Sports/ Performing Arts Module, the two scoring systems strongly correlated and the results were statistically significant (p=0.0006), with a mean Mangled Extremity Severity Score of 6.1 and a mean Disabilities of the Arm, Shoulder and Hand Score of 39.1. To our knowledge, this is the first study that correlates these two assessment tools; thus, no direct comparison with literature is possible. Töpel et al.[8] evaluated the outcomes of 33 patients who had undergone arterial reconstruction for major upper extremity vascular injuries. Similar to our study, iatrogenic and injuries distal to the wrist joint were excluded. In Töpel’s study, 73% of all traumas involved arteries of the forearm, while in our patient population, the brachial artery was the most commonly injured vessel, which reflects the increased severity of injuries captured in our cohort. The authors compared the patients’ functional outcomes based on physical exams (e.g., range of wrist and finger motion) to the respective Disabilities of the Arm, Shoulder and Hand Scores and found a strong correlation between these two assessments. Patients showing severe functional deficits had a significantly higher Disabilities of the Arm, Shoulder and Hand Score (35.8 points) in comparison to participants with minor or no deficits (11.8 points). In our study, despite the involvement of more proximal vessels, the mean post-traumatic Disabilities of the Arm, Shoulder and Hand Score was lower, with an average of 30 points. However, in the subgroup of patients with prolonged ischemia time, a higher mean Disabilities of the Arm, Shoulder and Hand Score was observed (43.7 points). Töpel et al.[8] demonstrated a higher rate of functional deficits (56%) in patients with concomitant nerve injuries (27 patients/81%). In our study, the three patients who had sustained injuries of the brachial plexus also had the worst functional outcomes and the highest Disabilities of the Arm, Shoulder and Hand Scores (62.5, 75 and 94.2 points respectively). 99

Hohenberger et al. Traumatic upper extremity injuries

Joshi et al.[9] performed a retrospective review using the Disabilities of the Arm, Shoulder and Hand Score as the mean outcome assessment tool for 17 patients who had sustained blunt or penetrating upper extremity traumas with associated major arterial injuries. Comparable to our results, their patients were predominantly males and underwent reconstruction with vein grafts in the majority of cases. Furthermore, the most commonly affected vessel proved to be the brachial artery in 65% of cases, which was almost the same for our cohort (64%). Their limb salvage rate of 94%, which was also comparable to our patient series (100%). Higher, though not statistically significant, Disabilities of the Arm, Shoulder and Hand Scores were observed in the subgroup of patients who had suffered blunt trauma with a mean score of 61.8 points compared to patients with penetrating injuries, with a mean score of 22.8 points. The authors suggested that higher Disabilities of the Arm, Shoulder and Hand Scores in the blunt trauma group were the result of concomitant nerve and orthopaedic injuries, often associated with a crash or other types of blunt trauma. Interestingly, in our study, the means of the total Disabilities of the Arm, Shoulder and Hand Score between these two subgroups demonstrated minor differences (blunt: 31±32.4 points; penetrating: 27.5±14.7 points). Concomitant nerve injury was present in 64% (9/14) of our patients, which is relatively high in comparison to Klocker’s[10] results with 43% (38/89). Frech et al.[11] conducted a retrospective review of prospectively collected data, assessing the results of the Disabilities of the Arm, Shoulder and Hand Score of 65 patients who had sustained arterial reconstruction due to upper extremity injuries. Patients with associated nerve traumas scored significantly higher (mean of 40.3 points) in comparison to the group without nerve injuries (mean of 0.8 points). These findings were confirmed by our results (43.1 vs. 6.5 points, p=0.02). However, the authors of this study did not find worse clinical outcomes in patients with brachial plexus injuries in comparison to the subgroup with peripheral neural traumas, even though patients with such lesions showed the highest Disabilities of the Arm, Shoulder and Hand Scores in our study. The Mangled Extremity Severity Score was popularised by Johansen et al.[4] in 1990 as a simple and objective rating scale, determining the need for lower extremity amputation after significant vascular trauma.[12,13] Four different variables were included: skeletal and soft tissue injury, limb ischemia, shock, as well as patient age.[4] The score was designed in a civilian setting based on a retrospective analysis of 25 patients who had sustained mangled lower extremities and on a prospective study of an additional 26 trauma patients with devastating vascular lower extremity injuries.[4,14] During the retrospective analysis, the patients with salvaged extremities had a mean Mangled Extremity Severity Score of 4.9, whereas the amputation group had a mean of 9.1, which was significantly higher. These findings were confirmed by their prospective 100

trial, and the authors concluded that a value of seven or more points predicted amputation with 100% accuracy.[4,15] Up to now, the Mangled Extremity Severity Score has been applied to upper extremity injuries and has been evaluated for both upper and lower limbs.[1,2,5,6] The use of the Mangled Extremity Severity Score and the cut-off point of ≥7 points as an indicator for amputation remain controversial. Ege et al.[16] stated the Mangled Extremity Severity Score not to be predictive in combat-related upper extremity and lower extremity trauma, including open fractures. Similarly, Sheean et al.[17] demonstrated that a Mangled Extremity Severity Score of at least seven points has a positive predictive value of 50% only in patients with lower extremity traumas in the military setting and recommended against its use. On the contrary, Sharma et al.[12] suggested that a Mangled Extremity Severity Score ≥7 positively predicts the need for amputation in 100% of patients after examining 50 patients with mangled lower extremities. However, they found the score lacking prediction of successful extremity salvage and functional outcomes since many of the patients with a Mangled Extremity Severity Score <7 required delayed amputation. Prichayudh and colleagues[6] postulated that the decision for or against limb amputation should rather be based on individual clinical signs since they were able to avoid amputation in 12 out of 19 patients with limb threatening-upper extremity traumas with a Mangled Extremity Severity Score of at least 7. In Fochtmann et al.’s[18] evaluation of 93 third-degree open tibia shaft fractures, the Mangled Extremity Severity Score proved to be significantly higher in the subgroup requiring amputation. However, the authors concluded that the threshold of 7 points should be reassessed and possibly revised. In a follow-up study, Yeh et al.[19] suggested the additional use of the injury severity score (ISS) in cases of Mangled Extremity Severity Score between 7 and 9 points. If the ISS exceeds 18 points, amputation should be considered and if it is less than 18 points, salvage of the extremity should be attempted, with approximately 60% success rates based on the authors’ experience. In our study, none of the critically injured extremities underwent amputation, even though four patients had a Mangled Extremity Severity Score of at least seven points. Patients with borderline Mangled Extremity Severity Score of 7 or 8 points achieved satisfactory long-term results based on their postoperative total Disabilities of the Arm, Shoulder and Hand Scores (18.3 and 20.8, respectively). Regarding the highest Mangled Extremity Severity Score scores (10 and 11 points), both patients had sustained a complete rupture of the brachial plexus leading to motor and sensory dysfunction of the injured extremity. One patient had become incapable of working; however, he had also sustained paraplegia due to a burst fracture of the 12th thoracic vertebra, so it is difficult to draw conclusions regarding the actual cause of his disability. Regarding the threshold of 7 Mangled Extremity Severity Score points for amputation, 50% of our patients Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

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with Mangled Extremity Severity Score of 7 or higher had satisfactory functional outcomes and the other half had a sensorimotor deficit of the upper extremity as a result of their direct brachial plexus lesions. Concerning the limitations of our study, this study was a retrospective review with the inherent bias of this type of study. Also, our study sample was small and it concerned exclusively civilian traumas. Therefore, our results can only be compared to studies that have included patients with similar injury mechanisms. Furthermore, follow-up time was variable, ranging from 17 to 124 months (mean 70.1 months; SD 35.8). In conclusion, in patients with vascular trauma of the upper extremity, the Disabilities of the Arm, Shoulder and Hand Score Sports/Performing Arts Module correlate positively and significantly with the respective Mangled Extremity Severity Score. Furthermore, the Disabilities of the Arm, Shoulder and Hand Score correlated positively and significantly with the Mangled Extremity Severity Score in patients with prolonged ischemia time (>6 hours); therefore, we assume ischemia time to be more relevant than the other items of the Mangled Extremity Severity Score. The use of a Mangled Extremity Severity Score of 7 or more points as an indication for primary amputation is not justified, as half of our patients with a Mangled Extremity Severity Score ≥7 achieved satisfactory functional outcomes at long term follow-up. Thus, we recommend vascular reconstruction with any Mangled Extremity Severity Score as long as residual functionality seems reasonable. Early intervention and decreased ischemia time may increase the chances of limb salvage. Further studies, including more patients, should be conducted to verify our results and lead to firm conclusions regarding accurate predictors of poor outcomes, indicating amputation in patients suffering such injuries. Ethics Committee Approval: Approved by the local ethics committee (EC number: 1298/2015). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: G.M.H., P.K., T.C.; Design: G.M.H., P.K., T.C.; Supervision: F.J.S., T.C.; Materials: G.M.H., J.C.D., S.B., A.M.S.; Data: G.M.H., J.C.D., S.B., A.M.S.; Analysis: P.K.; Literature search: G.M.H., J.C.D.; Writing: G.M.H., P.K.; Critical revision: J.C.D., A.M.S., S.B., F.J.S., P.K., T.C. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Prasarn ML, Helfet DL, Kloen P. Management of the mangled extremity. Strategies Trauma Limb Reconstr 2012;7:57−66.

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2. Bernstein ML, Chung KC. Early management of the mangled upper extremity. Injury 2007;8 Suppl 5:S3−7. 3. Korompilias AV, Beris AE, Lykissas MG, Vekris MD, Kontogeorgakos VA, Soucacos PN. The mangled extremity and attempt for limb salvage. J Orthop Surg Res 2009;4:4. 4. Johansen K, Daines M, Howey T, Helfet D, Hansen ST Jr. Objective criteria accurately predict amputation following lower extremity trauma. J Trauma 1990;30:568−72. 5. Mommsen P, Zeckey C, Hildebrand F, Frink M, Khaladj Nawid, Lange N, et al. Traumatic extremity arterial injury in children: epidemiology, diagnostics, treatment and prognostic value of Mangled Extremity Severity Score. J Orthop Surg Res 2010;5:25. 6. Prichayudh S, Verananvattna A, Sriussadaporn S, Sriussadaporn S, Kritayakirana K, Pak-art R, et al. Management of upper extremity vascular injury: outcome related to the Mangled Extremity Severity Score. World J Surg 2009;33:857−63. 7. Gummesson C, Atroshi I, Ekdahl C. The disabilities of the arm, shoulder and hand (DASH) outcome questionnaire: longitudinal construct validity and measuring self-rated health change after surgery. BMC Musculoskelet Disord 2003;4:11. 8. Töpel I, Pfister K, Moser A, Stehr A, Steinbauer M, Prantl L, et al. Clinical outcome and quality of life after upper extremity arterial trauma. Ann Vasc Surg 2009;3:317−23. 9. Joshi V, Harding GE, Bottoni DA, Lovell MB, Forbes TL. Determination of functional outcome following upper extremity arterial trauma. Vasc Endovascular Surg 2007;41:111−4. 10. Klocker J, Falkensammer J, Pellegrini L, Biebl M, Tauscher T, Fraedrich G. Repair of arterial injury after blunt trauma in the upper extremity - immediate and long-term outcome. Eur J Vasc Endovasc Surg 2010;39:160−4. 11. Frech A, Pellegrini L, Fraedrich G, Goebel G, Klocker J. Long-term clinical outcome and functional status after arterial reconstruction in upper extremity injury. Eur J Vasc Endovasc Surg 2016;52:119−23. 12. Sharma S, Devgan A, Marya KM, Rathee N. Critical evaluation of mangled extremity severity scoring system in Indian patients. Injury 2003;34:493−6. 13. Togawa S, Yamami N, Nakayama H, Mano Y, Ikegami K, Ozeki S. The validity of the mangled extremity severity score in the assessment of upper limb injuries. J Bone Joint Surg Br 2005;87:1516−9. 14. Schirò GR, Sessa S, Piccioli A, Maccauro G. Primary amputation vs limb salvage in mangled extremity: a systematic review of the current scoring system. BMC Musculoskelet Disord 2015;16:372. 15. Shanmuganathan R. The utility of scores in the decision to salvage or amputation in severely injured limbs. Indian J Orthop 2008;42:368−76. 16. Ege T, Unlu A, Tas H, Bek D, Turkan S, Cetinkaya A. Reliability of the mangled extremity severity score in combat-related upper and lower extremity injuries. Indian J Orthop 2015;49:656−60. 17. Sheean AJ, Krueger CA, Napierala MA, Stinner DJ, Hsu JR; Skeletal Trauma and Research Consortium (STReC). Evaluation of the mangled extremity severity score in combat-related type III open tibia fracture. J Orthop Trauma 2014;28:523−6. 18. Fochtmann A, Mittlböck M, Binder H, Köttstorfer J, Hajdu S. Potential prognostic factors predicting secondary amputation in third-degree open lower limb fractures. J Trauma Acute Care Surg 2014;76:1076−81. 19. Yeh HK, Fang F, Lin YT, Lin CH, Lin CH, Hsu CC. The effect of systemic injury score on the decision making of mangled lower extremities. Injury 2016;47:2127−30.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Travmatik üst ekstremite yaralanmaları: Ekstremite hasarlanması şiddet skoru ve kol, omuz ve el sakatlıkları arasında korelasyon analizi Dr. Gloria Maria Hohenberger,1 Dr. Janos Cambiaso-Daniel,2 Dr. Angelika Maria Schwarz,3 Dr. Stafanos Boukovalas,4 Dr. Franz Josef Seibert,1 Dr. Peter Konstantiniuk,5 Dr. Tina Cohnert5 Graz Tıp Fakültesi Ortopedi ve Travma Cerrahisi Anabilim Dalı, Graz-Avusturya Graz Tıp Fakültesi, Cerrahi Anabilim Dalı, Rekonstrüktif ve Estetik Cerrahi Bölümü, Graz-Avusturya AUVA Travma Hastanesi Graz, Graz-Avusturya 4 Teksas Üniversitesi Tıp Fakültesi, Plastik Cerrahi Anabilim Dalı, Galveston, Teksas-ABD 5 Graz Tıp Fakültesi, Cerrahi Anabilim Dalı, Damar Cerrahisi Bölümü, Graz-Avusturya 1 2 3

AMAÇ: Ekstremite Hasarlanması Şiddet Skoru, travma sonrası ekstremite ampütasyonu için bir karar verme aracıdır. Üst ekstremitenin travma sonrası fonksiyonel eksikliklerini ölçmek için Kol, Omuz ve El Yetersizlikleri Anketi geliştirilmiştir. Bu çalışma bu iki değerlendirme arasındaki korelasyonu belirlemeyi amaçlamaktadır. GEREÇ VE YÖNTEM: Bu çalışmada, 2005–2014 yılları arasında iki merkezde vasküler rekonstrüksiyon ile tedavi edilen üst ekstremite yaralanması olan tüm hastalar geriye dönük olarak gözden geçirildi. Her katılımcı için ilgili Ekstremite Hasarlanması Şiddet Skoru hesaplandı. Hastalar takip muayenesi ve Kol, Omuz ve El Skoru Yetersizliklerinin değerlendirilmesi için geri çağrıldı. BULGULAR: Bu çalışmada 14 hasta dahil edilme kriterlerini karşılamıştır. Ortalama toplam Ekstremite Hasarlanması Şiddet Skoru 5.9 ve Kol, Omuz ve El Yetersizlik Skoru 30 puan idi. Bu değerlendirmeler arasında istatistiksel olarak anlamlı bir ilişki yoktu (Spearman sıralaması korelasyon katsayısı: 0.49, p=0.075). TARTIŞMA: Kol, Omuz ve El Yetersizlikleri Skoru Ekstremite Harabiyeti Şiddet Skoruyla korelasyon göstermemiştir. Anahtar sözcükler: Amputasyon; hasarlanmış ekstremite; üst ekstremite travması; vasküler travma. Ulus Travma Acil Cerrahi Derg 2020;26(1):95-102

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doi: 10.14744/tjtes.2019.44939

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ORIGIN A L A R T IC L E

Endoscopic treatment of postoperative biliary fistulas Şükrü Çolak, M.D.,1 Ekrem Çakar, M.D.,1

Bünyamin Gürbulak, M.D.,1 Hasan Bektaş, M.D.1

Ali Fuat Kaan Gök, M.D.,2

Department of General Surgery, İstanbul Training and Research Hospital, İstanbul-Turkey

Department of General Surgery, İstanbul University İstanbul Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: Biliary fistula is one of the most common complications of liver and biliary tract surgeries. Endoscopic retrograde cholangiopancreatography (ERCP) is used for the diagnosis and treatment of biliary fistulas. In this study, we aimed to analyze the contribution of ERCP in this regard. METHODS: Patients who underwent ERCP for biliary fistulas following liver and biliary tract surgery between January 2012 and December 2017 were included in this study. The demographic characteristics of the patient, surgical procedure, localization of the biliary fistula, classification of biliary duct injury, and success of ERCP were retrospectively evaluated. RESULTS: In total, 90 patients (37 male and 53 female) with a diagnosis of biliary fistula underwent ERCP. Common biliary duct (CBD) cannulation was achieved in 87 patients using ERCP. In five patients, the proximal part of the biliary tract was not visualized, and complete injury of CBD was considered. In ERCP, contrast extravasation was detected in the cystic duct in 44 patients: CBD, eight patients; liver bed, four patients; hepatic duct bifurcation, two patients; the right hepatic canal, seven patients; and the left hepatic canal, two patients. CONCLUSION: ERCP is an effective method for the diagnosis and treatment of biliary diseases. The diagnosis and treatment of postoperative biliary fistulas with ERCP reduces surgery cost, morbidity, and mortality. Keywords: Biliary fistula; biliary stents; ERCP.

INTRODUCTION Many complications occur following liver and biliary tract surgeries, which includes that wound site infections, iatrogenic vascular and biliary injuries, and anastomotic leakage. Generally, the biliary injuries are iatrogenic and may be noticed during operation or in the postoperative follow-up period. Most of the iatrogenic biliary tract injuries cannot be detected during surgery.[1] Concerning mortality and morbidity, perioperative noticeable biliary injuries are more advantageous concerning managing the complication than those observed in the postoperative period.[2,3] Biliary fistula most commonly occurs after cholecystectomy. The rate of biliary tract injuries observed during laparoscopic cholecystectomy is higher than that open cholecystectomy.[4,5] The

incidence of biliary injury in laparoscopic cholecystectomy has been reported to vary from 0.5% to 0.9% in different series.[6] Biliary fistulas can be observed following liver resections, surgical procedures for hydatid cysts, blunt and penetrating liver injuries, and liver biopsies. Other causes includes that liver transplantation with biliary duct anastomosis and surgical interventions for periampullary tumors. The time, patient’s condition, radiological and laboratory findings of biliary fistulas play an important role in the treatment strategy. Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced endoscopic method used for the diagnosis and treatment of biliary tract and pancreatic diseases. This study aims to evaluate the contribution of ERCP in the

Cite this article as: Çolak Ş, Gürbulak B, Gök AFK, Çakar E, Bektaş H. Endoscopic treatment of postoperative biliary fistulas. Ulus Travma Acil Cerrahi Derg 2020;26:103-108. Address for correspondence: Bünyamin Gürbulak, M.D. İstanbul Eğitim ve Araştırma Hastenesi, Genel Cerrahi Kliniği, 34090 Fatih, İstanbul, Turkey Tel: +90 212 - 488 30 25 E-mail: bgurbulak@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):103-108 DOI: 10.14744/tjtes.2019.63667 Submitted: 31.01.2019 Accepted: 15.03.2019 Online: 02.01.2020 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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diagnosis and treatment of patients admitted because of the biliary fistulas.

MATERIALS AND METHODS This study included 90 patients who were diagnosed with biliary fistula following cholecystectomy or hepatobiliary surgery and had undergone an ERCP procedure in our endoscopy unit between January 2012 and December 2017. The patients were informed about biliary fistulas, treatment options, and ERCP complications; they were evaluated by an anesthesiologist based on the American Society of Anesthesiologists score. The type of sedation and dosage of medication were determined and administered under the control of the anesthesiologist. Age, gender, type of surgery, postoperative period, physical examination findings, and daily drainage (cc) of bile were recorded. Data regarding the cannulation rates of the common biliary duct (CBD) and pancreatic duct, location of the contrast extravasation, type of injury, filling defects in CBD, endoscopic treatment method, type and size of the endobiliary stents were recorded. In the postoperative period, the type and time of radiological imaging were determined based on the amount of biliary fistula. A daily volume of 500 cc of biliary drainage was accepted as a threshold value based on the classical fistula flow definition. If the fistula flow rate and biochemical values were high, the patient was evaluated by upper abdominal magnetic resonance (MR) and MR cholangiography. If the fistula flow was low and continued for a few days, the patient was evaluated by abdominal ultrasonography (USG), and ERCP was performed. Fistulas were classified based on the level of contrast extravasation in ERCP. The Strasberg classification was used for iatrogenic biliary injuries during cholecystectomy (Table 1). The treatment of patients was planned according to this classification. Preoperative anatomic localization, diameter, and type (based on the Gharbi classification) of the cyst were

recorded in patients who underwent hydatid cyst surgery. The endoscopic treatment was considered successful if the cessation of biliary fistula and radiological, clinical, and laboratory findings of the patient were improved folllowing the ERCP. Multiple ERCPs were performed for stent removal in patients and for those who developed a biliary stricture. Informed consent was obtained from all the patients included in this study. The study was conducted, and data were collected according to the ethical principles of the Declaration of Helsinki.

Statistical Methods Descriptive statistical methods, such as mean ± standard deviation and/or median (minimum–maximum) and frequency and percentage, were used for data evaluation. The statistical analysis was performed using the Statistical Package for Social Sciences (SPSS®) software package for Windows, version 17.0 (SPSS Inc., Chicago, Illinois, USA).

RESULTS A total of 90 patients comprising 37 (41.1%) males and 53 (58.9%) females were admitted to the endoscopy unit with the diagnosis of postoperative biliary fistula. Overall, 54 patients were referred from other centers, and 36 patients were operated in our clinic. Biliary drainage was noted in 85 patients upon admission. The clinical symptoms of the patients most commonly included biliary fistula in 77 (85.5%) patients, abdominal pain in 46 (51.1%), jaundice in 25 (27.7%), biloma in 10 (11.1%), and peritonitis in three (3.3%). While 65 patients had normal liver function tests, 25 had elevated cholestasis enzymes and bilirubin levels. CBD cannulation was achieved in 87 of patients but; it was not succesfully in two of patients because of pyloric stenosis

Table 1. Strasberg classification Type Patients (n)

104

Female

Definition

Male

70.5

–

Cystic duct or small biliary ducts in the liver bed

–

Transection without ligation of the aberrant right hepatic duct

Lateral injury to the major bile duct

Occlusion of the aberrant right hepatic duct

7.3

Transection >2 cm from the hilum

–

Transection <2 cm from the hilum

–

Transection in the hilum

–

Separation of major ducts in the hilum

–

Type C injury plus injury in the hilum

–

Total

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Table 2. Age, gender, and ASA classification of patients

Table 4. Biliary stricture, multiple ERCPs, and stenting

Female Male

Patient, n (%)

53 (58.9)

37 (41.1)

50.47

55.02

Age (years) Cannulation of CBD, n (%)

Female

Male

Total

CBD

2 2 4

Dilatation

1 2 3/4

52 (98.1)

35 (94.6)

Multiple stenting

ASA I

SEMS

1 2 3/4

ASA II

Bifurcation

1 0 1

ASA III

Dilatation

1 0 1/1

Stenting

1 0 1/1

Right hepatic duct

Dilatation

1 1 2/3

Stenting

1 1 2/3

ASA: American Society of Anesthesiologists; CBD: Common biliary duct.

Table 3. Patients and ERCP procedures Hydatid cyst Daughter cyst in CBD ES/stenting Hepatectomy ES/stenting Metastasectomy ES/stenting

Female

Male

Total

5/2 3/1 8/3 1 2 3 1/1 2/0 3/1 0 1 1 0/0 1/1 1/1

Liver trauma

ES/stenting

0/0

1/0

Cholecystectomy ES/stenting Stone in CBD Choledochotomy ES/stenting

47 29 76 43/37 26/17 69/54 7

0 1 1 0/0 1/1 1/1

ES: Endoscopic Sphincterotomy; ERCP: Endoscopic retrograde cholangiopancreatography; CBD: Common biliary duct.

and in one patient because of technical reasons. The biliary tract was normal, and no contrast extravasation detected in seven patients (Table 2). ERCP was performed in 76 (84.4%) patients following cholecystectomy, eight (8.8%) patients following hydatid cyst surgery, three patients following hepatic resection, one patient following metastasectomy, one patient with penetrating liver injury, and one patient with choledocholithiasis (Table 3). While the distal biliary tract was imaged in five patients, the visualiation of the proximal part of it could not be imaged, and complete injury of CBD was considered. These five patients subsequently underwent percutaneous transhepatic biliary drainage under the guidance of USG. In ERCP, extravasation of the contrast medium was detected in the cystic duct in 44 patients: CBD in eight, liver bed in Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

3/4

SEMS: Self expandable metallic stent; ERCP: Endoscopic retrograde cholangiopancreatography; CBD: Common biliary duct.

four, hepatic duct bifurcation in two, the right hepatic canal in seven, and the left hepatic canal in two patients. Following hydatid cyst surgery, biliary fistula was present in eight patients, six fistulas were from the right hepatic lobe and two from the left hepatic lobe. According to the Gharbi classification, in the preoperative period, seven patients were classified as type 3 and one as type 2. Endoscopic sphincterotomy (ES) was not performed in three patients which could not be cannulated and in five patients with complete CBD injury. Eighty-two patients underwent ES and 59 underwent biliary stenting. Stents were removed in an average of 65 days (18â&#x20AC;&#x201C;360 days). A biliary stricture developed in eight patients who had lateral injuries of the main biliary duct, which improved with a biliary stent. These patients underwent ERCP 3 to 7 times for the stricture. Plastic stents were used in seven patients, and self-expendable metallic stents (SEMS) were used in three patients (Table 4). In our study, the most common biliary fistula was from the cystic duct and gallbladder bed following cholecystectomy. Low flow biliary fistula was detected in 67 (74.4%) patients. The Strasberg Type A biliary duct injury was found in 48 (70.5%) patients. Succesfully teratment was achieved for biliary fistulas in 79 (88.8%) of patients who underwent ERCP.

DISCUSSION Biliary fistulas can be observed in many procedures involving the liver and bile ducts. There is a correlation between biliary fistula and the operation. For example, the biliary fistula rate varies from 3.6% to 10% following hepatectomy, and the rate of biliary fistula has been reported to be 8% in hepaticojejunostomy with pancreaticoduodenectomy.[7,8] The rate of biliary fistula and stricture were reported to be 8.5% and 14.7%, respectively, after liver transplantation.[9] The rate of the biliary fistula 105

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is reported to be 5% to 63% following hydatid cyst surgery[10,11] and 0.5% to 21% following liver trauma.[12,13] The incidence of biliary injury in laparoscopic cholecystectomy has been reported to vary between 0.5% to 0.9% in different series. The first laparoscopic cholecystectomy was performed by Erich Mühe in 1985.[14] The rate of biliary injury is higher in laparoscopic cholecystectomy than open cholecystectomy because of the 2-dimensional appearance and a longer learning curve.[15] According to the principles of “critical view of safety,” the dissection of the Calot’s triangle should be carefully performed, and the gallbladder should be released from the liver bed. The cystic duct and artery should not be clipped and divided when the critical view of safety is not anatomically achieved.[16,17] The mechanisms of these biliary tract injuries in laparoscopic cholecystectomy are well-defined. The most common condition is that the main biliary and cystic ducts cannot be identified because of the inability to dissect the Calot’s triangle. This condition can be because of the congenital anatomical anomalies as well as severe adhesion caused by inflammation, obesity, and gallbladder neoplasm.[18–21] Factors related to the skill and experience of the surgeon include unnecessary dissections of the Calot’s triangle, use of cautery near the biliary ducts, and excessive traction of the gallbladder.[22] Biliary fistulas can be observed after cholecystectomy because of the extra biliary ducts that directly opened to the gallbladder; Oddi sphincter dysfunction without biliary duct injury or various type of injuries in the biliary tract. If a biliary fistula occurs after a biliary duct injury, it may lead to a biliary duct stricture after recovery. The management of this complication is quite difficult for physicians.[23] Biliary tract injury can be simple and treatable with a minimally invasive approach, such as ERCP, or may require a complex surgery because of high flow biliary fistula. Common symptoms of biliary fistulas include biliary drainage, abdominal pain, jaundice, fever, acid, and bilomas. Although most biliary fistulas are observed in the first week following surgery, this period may be extended up to three months.[24] Radiological methods, such as USG, computerised tomography, MR cholangiopancreatography, can be used to evaluate the biliary fistulas. ERCP was first used as a diagnostic tool in 1968. The first biliary stent was used in a patient with jaundice in 1980.[25] Thus, ERCP was used from the diagnosis to treatment stages. Recently, ERCP has an important role in the treatment of complications of surgery. The main functions of ERCP in biliary fistulas are to decrease the pressure in the biliary tract using sphincterotomy or biliary stents, prevent biliary leakage into the abdominal cavity, and direct the bile to the bowel lumen, which reduces the mortality and morbidity rates by protecting patients from localized and generalized peritonitis. The treatment approach in ERCP is determined by the type and localization of fistula in cholangiography, the amount of fistula (cc), stone and stricture associated with the injury. The most successful treatment of biliary fistulas is achieved through ERCP for the type of Strasberg A–D injuries. The most common cause of biliary fistulas was chole106

cystectomy because of cholelithiasis in 76 patients (84.4%). Four of these patients had a conversion from laparoscopic to open surgery. Choledocholithiasis was detected in 16 (21%) of the 76 patients. This finding may be because of spontaneous passage of stone to CBD before the procedure or because these patients may have secondary Oddi sphincter dysfunction. The second most common cause was hydatid cyst surgery in eight (8.8%) patients. Only two of these patients were detected with daughter cysts in CBD, which were extracted using ERCP. Hepatic resection was present in four (4.4%) patients. One patient (1.1%) had penetrating liver injury, and one (1.1%) patient underwent choledochotomy for choledocholithiasis. In the patient who underwent choledochotomy, closure of the fistula failed because of a stricture in distal choledochotomy one month following the operation. A biliary stent was placed after sphincterotomy, and multiple dilatations were performed because of the stricture. In our study, the most common location for biliary fistula was the cystic stump and gallbladder bed after cholecystectomy. Low flow biliary fistula was detected in 67 (74.4%) patients. The Strasberg Type A bile duct injury was found in 48 (70.5%) patients. Eighty-two (91.1%) patients underwent sphincterotomy, and 59 (65.5%) patients underwent biliary stenting. Eight patients with an injury of the right hepatic duct and two patients with an injury of bifurcation had 8.5 French 12-cm plastic biliary stents placed in both the right and left main hepatic ducts. For the other patients, 10 French 10-cm plastic biliary stents were used. Animal studies that evaluated the pressure gradient between CBD and the duodenum after sphincterotomy or stenting and have shown that the intrabiliary pressure was more effectively decreased in the stenting group than the ES group. [26] Other clinical and experimental studies have shown that biliary stenting with ES is more effective than ES alone in reducing the Oddi sphincter pressure.[27,28] The efficacy of ERCP in biliary injuries, leading to biliary fistulas, is reported to be 85%–95%.[29,30] The efficacy of ERCP in postoperative biliary fistulas was 88.8% in our series. Data regarding the stricture formation of the bile duct after the improvement of injuries are limited. In our series, 28 patients had major biliary tract injuries. Fifteen of these patients had a lateral injury of CBD, and these patients were treated without complications by ERCP. In eight of these patients, a stricture developed in CBD. For these patients, multiple dilatations and plastic biliary stenting were performed, and SEMS were used in two patients. In conclusion, postoperative biliary fistulas are complications that may be associated with high mortality and morbidity. Our experiences showed that ERCP was an effective method for diagnosing and treating the biliary fistulas following surgery. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Çolak et al. Endoscopic treatment of postoperative biliary fistulas

ERCP assists in managing the biliary duct strictures, prevents additional operations, and offers significant advantages concerning mortality, morbidity, and cost. Ethics Committee Approval: Retrospective study. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: Ş.Ç., H.B.; Design: Ş.Ç., B.G.; Supervision: H.B.; Materials: Ş.Ç., E.Ç.; Data: Ş.Ç., E.Ç.; Analysis: A.F.K.G., B.G.; Literature search: A.F.K.G., B.G.; Writing: B.G., Ş.Ç.; Critical revision: B.G., H.B. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Bergman JJ, van den Brink GR, Rauws EA, de Wit L, Obertop H, Huibregtse K, et al. Treatment of bile duct lesions after laparoscopic cholecystectomy. Gut 1996;38:141−7. 2. Martin RF, Rossi RL. Bile duct injuries. Spectrum, mechanisms of injury, and their prevention. Surg Clin North Am 1994;74:781−807. 3. Sandha GS, Bourke MJ, Haber GB, Kortan PP. Endoscopic therapy for bile leak based on a new classification: results in 207 patients. Gastrointest Endosc 2004;60:567−74. 4. Roslyn JJ, Binns GS, Hughes EF, Saunders-Kirkwood K, Zinner MJ, Cates JA. Open cholecystectomy. A contemporary analysis of 42,474 patients. Ann Surg 1993;218:129−37. 5. Strasberg SM, Hertl M, Soper NJ. An analysis of the problem of biliary injury during laparoscopic cholecystectomy. J Am Coll Surg 1995;180:101−25. 6. Adamsen S, Hansen OH, Funch-Jensen P, Schulze S, Stage JG, Wara P. Bile duct injury during laparoscopic cholecystectomy: a prospective nationwide series. J Am Coll Surg 1997;184:571−8. 7. Ishii H, Ochiai T, Murayama Y, Komatsu S, Shiozaki A, Kuriu Y, et al. Risk factors and management of postoperative bile leakage after hepatectomy without bilioenteric anastomosis. Dig Surg 2011;28:198−204. 8. Qiu H, Zhang J, Qian HG, Leng JH, Wu JH, Liu BN, et al. Hepaticojejunostomy leak after pancreaticoduodenectomy. Int Surg J 2016;3:603−8. 9. Nemes B, Gámán G, Doros A. Biliary complications after liver transplantation. Expert Rev Gastroenterol Hepatol 2015;9:447−66. 10. Kayaalp C, Bzeizi K, Demirbag AE, Akoglu M. Biliary complications after hydatid liver surgery: incidence and risk factors. J Gastrointest Surg 2002;6:706−12. 11. Adas G, Arikan S, Gurbuz E, Karahan S, Eryasar B, Karatepe O, et al. Comparison of endoscopic therapeutic modalities for postoperative biliary fistula of liver hydatid cyst: a retrospective multicentric study. Surg Laparosc Endosc Percutan Tech 2010;20:223−7. 12. Christmas AB, Wilson AK, Manning B, Franklin GA, Miller FB, Richardson JD, et al. Selective management of blunt hepatic injuries including nonoperative management is a safe and effective strategy. Surgery 2005;138:606−10. 13. Asensio JA, Roldán G, Petrone P, Rojo E, Tillou A, Kuncir E, et al. Operative management and outcomes in 103 AAST-OIS grades IV and V complex hepatic injuries: trauma surgeons still need to operate, but an-

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gioembolization helps. J Trauma 2003;54:647−53; discussion 653−4. 14. Litynski GS. Highlights in the History of Laparoscopy. Frankfurt, Germany: Barbara Bernert Verlag; 1996. p. 165–8. 15. Roy PG, Soonawalla ZF, Grant HW. Medicolegal costs of bile duct injuries incurred during laparoscopic cholecystectomy. HPB (Oxford) 2009;11:130−4. 16. Wu YV, Linehan DC. Bile Duct Injuries in the era of laparoscopic cholecystectomies. Surg Clin North Am 2010;90:787−802. 17. Buddingh KT, Morks AN, ten Cate Hoedemaker HO, Blaauw CB, van Dam GM, Ploeg RJ, et al. Documenting correct assessment of biliary anatomy during laparoscopic cholecystectomy. Surg Endosc 2012;26:79−85. 18. Larson GM, Vitale GC, Casey J, Evans JS, Gilliam G, Heuser L, et al. Multipractice analysis of laparoscopic cholecystectomy in 1983 patients. Am J Surg 1992;163:221−6. 19. Scott TR, Zucker KA, Bailey RW. Laparoscopic cholecystectomy: a review of 12,397 patients. Surg Laparosc Endosc 1992;2:191−8. 20. Krähenbühl L, Sclabas G, Wente MN, Schäfer M, Schlumpf R, Büchler MW. Incidence, risk factors, and prevention of biliary tract injuries during laparoscopic cholecystectomy in Switzerland. World J Surg 2001;25:1325−30. 21. Barkun AN, Rezieg M, Mehta SN, Pavone E, Landry S, Barkun JS, et al. Postcholecystectomy biliary leaks in the laparoscopic era: risk factors, presentation, and management. McGill Gallstone Treatment Group. Gastrointest Endosc 1997;45:277−82. 22. Malik AM, Laghari AA, Talpur AH, Khan A. Iatrogenic biliary injuries during laparoscopic cholecystectomy. A continuing threat. Int J Surg 2008;6:392−5. 23. Rerknimitr R, Sherman S, Fogel EL, Kalayci C, Lumeng L, Chalasani N, et al. Biliary tract complications after orthotopic liver transplantation with choledochocholedochostomy anastomosis: endoscopic findings and results of therapy. Gastrointest Endosc 2002;55:224−31. 24. Davidoff AM, Pappas TN, Murray EA, Hilleren DJ, Johnson RD, Baker ME, et al. Mechanisms of major biliary injury during laparoscopic cholecystectomy. Ann Surg 1992;215:196−202. 25. Soehendra N, Reynders-Frederix V. Palliative bile duct drainage - a new endoscopic method of introducing a transpapillary drain. Endoscopy 1980;12:8−11. 26. Katsinelos P, Kountouras J, Paroutoglou G, Chatzimavroudis G, Germanidis G, Zavos C, et al. A comparative study of 10-Fr vs. 7-Fr straight plastic stents in the treatment of postcholecystectomy bile leak. Surg Endosc 2008;22:101−6. 27. Youngelman DF, Marks JM, Ponsky T, Ponsky JL. Comparison of bile duct pressures following sphincterotomy and endobiliary stenting in a canine model. Surg Endosc 1997;11:126−8. 28. Kim KH, Kim TN. Endoscopic management of bile leakage after cholecystectomy: a single-center experience for 12 years. Clin Endosc 2014;47:248−53. 29. Kaffes AJ, Hourigan L, De Luca N, Byth K, Williams SJ, Bourke MJ. Impact of endoscopic intervention in 100 patients with suspected postcholecystectomy bile leak. Gastrointest Endosc 2005;61:269−75. 30. Chow S, Bosco JJ, Heiss FW, Shea JA, Qaseem T, Howell D. Successful treatment of post-cholecystectomy bile leaks using nasobiliary tube drainage and sphincterotomy. Am J Gastroenterol 1997;92:1839−43.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Ameliyat sonrası safra fistüllerinin endoskopik tedavisi Dr. Şükrü Çolak,1 Dr. Bünyamin Gürbulak,1 Dr. Ali Fuat Kaan Gök,2 Dr. Ekrem Çakar,1 Dr. Hasan Bektaş1 1 2

İstanbul Eğitim ve Araştırma Hastenesi, Genel Cerrahi Kliniği, İstanbul İstanbul Üniversitesi İ̇stanbul Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul

AMAÇ: Safra fistülü, karaciğer ve safra yolu ameliyatlarında en sık görülen komplikasyonlardan biridir. Endoskopik retrograd kolanjiyopankreatografi (ERCP) biliyer fistüllerde tanı ve tedavi amaçlı kullanılır. ERCP’nin biliyer fistüllerin tanı ve tedavisinde katkısını analiz etmeyi amaçladık. GEREÇ VE YÖNTEM: Bu çalışmaya Ocak 2012–Aralık 2017 tarihleri arasında karaciğer ve safra yolu ameliyatlarını takiben gelişen safra fistüllerinde ERCP uygulanan hastalar dahil edildi. Hastaların demografik özellikleri, cerrahi prosedür, safra fistül lokalizasyonu, safra yolu yaralanmasının sınıflandırılması ve ERCP başarısı geriye dönük olarak değerlendirildi. BULGULAR: Toplam 90 hastaya (37 erkek ve 53 kadın) biliyer fistül tanısı ile ERCP uygulandı. ERCP ile 87 hastada ortak safra kanalı (CBD) kanülasyonu sağlandı. Beş hastada, safra yollarının proksimal kısmı görüntülenemedi ve ortak safra kanalının tam kat yaralanması düşünüldü. ERCP’de, 44 hastada sistik kanal, sekiz hastada ortak safra kanalı, dört hastada karaciğer yatağı, iki hastada hepatik kanal bifürkasyon, yedi hastada sağ hepatik kanal ve iki hastada sol hepatik kanal düzeyinde kontrast ekstravazasyonu tespit edildi. TARTIŞMA: Endoskopik retrograd kolanjiyopankreatografi biliyer hastalıkların tanı ve tedavisinde etkili bir yöntemdir. ERCP ile tanı konabilen ve tedavi edilebilen ameliyat sonrası biliyer fistüllerin tedavisi hastaları morbidite, mortalite ve cerrahi maliyetlerinden kurtarır. Anahtar sözcükler: Biliyer stentler; ERCP; safra fistülü. Ulus Travma Acil Cerrahi Derg 2020;26(1):103-108

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doi: 10.14744/tjtes.2019.63667

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ORIGIN A L A R T IC L E

The effects of early femoral nerve block intervention on preoperative pain management and incidence of postoperative delirium geriatric patients undergoing trochanteric femur fracture surgery: A randomized controlled trial Ali İhsan Uysal, M.D.,1 Başak Altıparmak, M.D.,4 Eylem Yaşar, M.D.,1 Mustafa Turan, M.D.,4 Umut Canbek, M.D.,2 Nigar Yılmaz, M.D.,3 Semra Gümüş Demirbilek, M.D.4 1

Department of Anesthesiology and Reanimation, Muğla Sıtkı Koçman University Training and Research Hospital, Muğla-Turkey

Department of Orthopedics and Traumatology, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla-Turkey

Department of Biochemstry, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla-Turkey

Department of Anesthesiology and Reanimation, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla-Turkey

ABSTRACT BACKGROUND: Hip fracture is a common clinical problem which causes severe pain in geriatric patients. However, severe pain following fracture may bring on mental disorders and delirium. A neuroinflammatory response with IL-6 and IL-8 has been shown to be associated with the pathophysiology of delirium. In this study, our primary hypothesis is that preoperative femoral nerve block (FNB) intervention in geriatric patients will more effectively attenuate pain following trochanteric femur fracture than the preoperative paracetamol application. Our secondary hypothesis is that interleukin levels (IL-6, IL-8) in cerebrospinal fluid (CSF) will be lower in the femoral nerve block group than the paracetamol group. Our tertiary hypothesis is that the incidence of postoperative delirium will be lower in the femoral nerve block group. METHODS: The patients over 65 years of age with ASA status II-IV and admitted to the Emergency Service for femur fracture were included in this study. Recommendations of the “delirium prevention table” were applied to all of the patients at arrival. In the first group, 15 mg/kg paracetamol was administered intravenously every eight hours. In the second group, femoral nerve blockage was performed, and a catheter was placed. Then, 0.5 mL/kg bupivacaine 0.25% was applied every eight hours. In both groups, pain scores four hours after interventions were recorded. All patients were operated within 48 hours under spinal anesthesia. During spinal anesthesia, 2 mL of CSF samples were taken from all patients for analysis of IL-6 and IL-8 cytokines, and pain scores during positioning were recorded. RESULTS: VAS scores four hours after the first preoperative pain treatment and during the positioning for regional anesthesia were significantly lower in the femoral nerve block group. IL-8 levels are significantly lower in the femoral nerve block group but not in IL-6 levels. The incidence of delirium was less in the femoral nerve block group, but the difference was not statistically significant. CONCLUSION: The femoral nerve block was more effective in preoperative pain management of trochanteric femur fracture and preventing pain during regional anesthesia application. The mean IL-8 level was lower in the femoral nerve block group when compared to the paracetamol group. There is no difference in the postoperative delirium incidence between groups. Keywords: Delirium; femoral nerve block; hip fracture; interleukin 8.

Cite this article as: Uysal Aİ, Altıparmak B, Yaşar E, Turan M, Canbek U, Yılmaz N, et al. The effects of early femoral nerve block intervention on preoperative pain management and incidence of postoperative delirium geriatric patients undergoing trochanteric femur fracture surgery: A randomized controlled trial. Ulus Travma Acil Cerrahi Derg 2020;26:109-114. Address for correspondence: Ali İhsan Uysal, M.D. Muğla Sıtkı Koçman Üniversitesi Eğitim Araştırma Hastanesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, 48000 Muğla, Turkey Tel: +90 252 - 214 13 23 E-mail: alihsanuysal@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):109-114 DOI: 10.14744/tjtes.2019.78002 Submitted: 15.10.2018 Accepted: 27.02.2019 Online: 27.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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INTRODUCTION Hip fracture is a common clinical problem in geriatric patients with a high mortality rate. The incidence of severe pain in the first 24 hours after femur fractures is 50–70%.[1] Previous studies[2,3] reported that the majority of patients with hip fracture had received inadequate pain treatment and almost 40% of the patients have never received any analgesic drugs in the preoperative period. However, it has been suggested that adequate pain treatment should be commenced before admittance to the hospital[4] since the severe pain following fracture may cause mental disorders and delirium.[5] Preoperative health status and cognitive functional capacity of the patients, neurotoxic effects of anesthetic agents, perioperative events during surgery and the used cement for prosthetic implantation are associated with postoperative cognitive problems.[6] Delirium is one of the most common complications in hospitalized elderly patients. Previous studies have shown that delirium is associated with both short and long-term poor outcomes. It is a medical condition that must be treated urgently because it significantly increases morbidity and mortality, prolongs the length of hospital stay, and may lead to a decrease in functional capacity.[7] The pathophysiological mechanisms of delirium are not precise, a neuroinflammatory response is suggested to play a role.[8] Up to date, many studies have analyzed different serum inflammatory markers in order to elucidate the pathophysiology of delirium.IL-6 and IL-8 have been shown to be associated with delirium.[9,10] In this study, our primary hypothesis is that preoperative femoral nerve block (FNB) intervention in geriatric patients will more effectively attenuate pain following trochanteric femur fracture than the preoperative paracetamol application. Our secondary hypothesis is that interleukin levels (IL-6, IL8) in cerebrospinal fluid (CSF) will be lower in the femoral nerve block group than the paracetamol group. Our tertiary hypothesis is that the incidence of postoperative delirium will be lower in the femoral nerve block group.

MATERIALS AND METHODS After the approval of the Muğla Sıtkı Koçman University, Clinical Research Ethics Committee in 17.05.2016 with a decision number 2016/50, 114 patients who were over 65 years of age with ASA status II-IV and admitted to the Emergency Department due to trochanteric femur fracture were included in this study. Patients with preexisting delirium at the admission to emergency service, femur fracture due to metastatic carcinoma, bupivacaine allergy, cholinesterase inhibitors or levodopa medication, parkinsonism or epilepsy, and a contraindication for nerve blockage were excluded from this study.

Ethics, Consent, and Permissions A written informed consent form was obtained from all patients who agreed to participate in this study. 110

Interventions The recommendations of the “delirium prevention table” defined by Björkelund et al.[11] were applied to all of the patients as soon as their arrival to the emergency service, oxygen support has been given at 3–4 lt/min and pulse oximeter measurements have been followed, a standard nutritional support was applied, hemoglobin values were raised above 10 gr/dL and hypo-hyperthermia were prevented in all cases. Preoperative cognitive functions of the patients were assessed by the 30-point Minimental Test (MMT). In the emergency service, patients were allocated into two groups. In the first group (Group I), 15 mg/ kg paracetamol within 15 min was administered intravenously. In the second group (Group II), intermittent FNB was performed in the emergency room. A high-frequency linear ultrasound probe (Fujifilm Sonosite, Bothwell, USA) was located in the inguinal area. When the femoral artery was found, the probe was moved slightly laterally to pinpoint the femoral nerve. When the ultrasonographic view of the femoral nerve was seen, the injection site was anesthetized with 2–3 mL of 2% lidocaine under aseptic conditions. An 80 mm 21-gauge plexus block needle (Stimuplex(R) B-Braun medical, Melsungen, Germany) was inserted in-plane view of the ultrasound probe. When a quadriceps muscle contraction was observed with a nerve stimulator (Braun Stimuplex® HNS 12), 10 ml of 0.25% bupivacaine was applied via a plexus block needle. Following block intervention, a nerve catheter was placed in the same site with ultrasound (USG) guidance.

Routine Analgesia and Pain Assessment After the initial pain treatment in the emergency service, patients were transferred to the surgical ward. In the first group, the paracetamol treatment was repeated every eight hours. In the second group, 0.5 mL/kg bupivacaine 0.25% was applied every eight hours via a femoral nerve catheter. If sufficient analgesia could not be achieved, 0.5 mg/kg tramadol was intravenously applied as rescue analgesia in both groups. The pain levels of all patients were assessed by 100-mm Visual Analogue Scale (VAS) and recorded at the 4th hour after initial pain treatment.

Anesthesia Procedure All patients were operated within 48 hours after admission to the hospital. If the operation was delayed more than 48 hours, the patients were excluded from this study. In the operation room, ECG, pulse oximeter and noninvasive blood pressure monitoring were performed. All patients were positioned for the spinal-epidural combined block. The pain occurred during positioning was assessed using VAS and recorded. During spinal anesthesia, 2 mL of CSF samples were taken from all of the patients. These samples were stored at -80º until the CSF specimens were analyzed for IL-6 and IL-8 cytokines using the enzyme-linked immunoassay method (sandwich method) in the Biochemistry Laboratory. For spinal anesthesia, 10 mg bupivacaine + 20 mcg fentanyl were administered intratheUlus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Uysal et al. Effect of early femoral nerve block on postoperative pain and delirium

cally. Following spinal anesthesia, femoral nerve catheters of patients in Group II were removed. After the operation, all patients received 0.125% bupivacaine + 100 mcg fentanyl through the epidural catheter with an infusion rate of 5 ml/h for postoperative pain control. Pain levels of patients were evaluated at the postoperative 1st, 4th, 12th and 24th hours by 100-mm VAS. The delirium status of patients was assessed using “Delirium Rating Scale-R-98 (DRS-R-98)” in the postoperative period for three days.

Evaluation of the Data The power analysis of the study was based on studies investigating the development of delirium after femur fracture operation. After the calculations were made with α=0.05 and 80% power (1-β=0.8), the number of patients required in each group was found to be 45. It was assumed that there could be a 20% drop out during the study; therefore, 55 patients were included in each group. For the statistical analysis, Statistical SPSS 20.0 (statistical package for social sciences for Windows 16.0) program was used. The normality tests of the distributions of the variables were performed using the Kolmogorov-Smirnov test. For numerical values with a normal distribution, the difference between the averages of the variables was evaluated using one-way ANOVA or Independent

Sample t-test. The Wilcoxon test was used for the analysis of the abnormally distributed variables. For all statistical tests, p <0.05 was considered statistically significant. Chi-square analysis was applied for categorical variables. Pearson test was applied for correlation.

RESULTS All in all, 110 patients were included in this study. Fourteen patients were excluded due to delay in the operation time, three patients died in the early postoperative period, and two patients were excluded due to change in anesthesia procedure. Consequently, 45 patients in Group I and 46 patients in Group II completed the study (Fig 1). The demographic variables of the patients are listed in Table 1. There was no significant difference between groups. Mean VAS scores at the 4th hour after first preoperative pain treatment and during the positioning for regional anesthesia were significantly lower in Group II (p<0.01). None of the patients’ required rescue analgesic in Group II. However, seven patients needed rescue analgesic in Group I (p≤0.05) during the preoperative period (Table 2). There was no significant difference regarding VAS scores during the postoperative period between groups (p>0.05) (Table 2).

ASA II-IV patients over 65 years of age who admitted to emergency department due to femur fracture (n=133) *13 patient inability to communicate *10 patient had emergency surgery for another reason Patients’ cognitive functions in the preoperative period were assessed by Minimental Test (MMT) and delirium prevention protocol was applied (n=110)

Group I Patients treated with parasetamol administration (n=55)

*2 patient: exitus in early postoperative period *8 patients: operation could not be performed in the first 48 hours

Patients who completed the study in Group I (n=45)

Group II Patients treated with femoral nerve block and nerve catheter insertion (n=55) *2 patients: turned to general anaesthesia *1 patient: exitus in early postoperative period *6 patients: operation could not be performed in the first 48 hours Patients who completed the study in Group II (n=46)

Figure 1. Operation chart.

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DISCUSSION

Table 1. Preoperative features of the patients

Group I Group II (n=45) (n=46)

Age

82.04±6.83 81.41±8.06

Gender (Female/Male)

25/20

26/20

Preop Minimental Test score

16.12±6.11

17.05±6.44

Preop delirium score

3.52±3.12

1.75±2.14

In the present study, early intermittent FNB was found to be more effective than intravenous paracetamol administration for pain management of geriatric patients following femur trochanteric fracture. However, there was no significant difference between groups concerning delirium development. Although mean IL-8 levels were significantly lower in the FNB group, mean IL-6 levels were similar between groups.

IL-8 levels were significantly lower in Group II than Group I (p<0.01). The mean level of IL-8 in patients who developed delirium in Group I was 0.1885±0.13 and in Group II was 0.111±0.025. The IL-6 levels were similar between groups (p>0.05) (Table 3).

One of the main problems after hip fracture is severe pain. Up until now, various methods have been used for both preoperative and postoperative pain management.[12] In the preoperative period, intravenous administration of non-steroid drugs and opioids[13,14] and performing nerve blocks[15,16] have been frequently used for pain control. However, pain after femur fracture may not arise solely from the hip joint. The damaged soft tissue after surgery is also a severe pain source, and intravenous agents may be inadequate in postoperative pain treatment. Therefore, the use of peripheral blocks in the preoperative period has gained popularity in recent years. Some previous studies reported that the fascia iliaca block could provide effective analgesia after femur fracture in the elderly.[16,17]

A negative correlation was detected between preoperative MMT scores and postoperative 1st, 2nd, 3rd hour delirium scores in both groups. This relation was statistically significant (1st day: r=-0.47, p<0.001, 2nd day: r=-0.49, p<0.001, 3rd day: r=-0.52, p<0.01).

Moreover, Kassam et al.[18] found the fascia iliaca block to provide a morphine-sparing effect in the preoperative period. In the present study, we aimed to apply an intermittent nerve block (instead of a single-shot block) by placing a nerve catheter; therefore, we preferred to perform FNB and provided bet-

According to assessment with DRS-R-98, the occurrence of delirium was less in group II (9 patients in Group I, five patients in Group II) in the early postoperative period. However, the difference was not statistically significant between groups (p>0.05).

Table 2. Preoperative, intraoperative, postoperative VAS scores and the number of patients who required preoperative rescue analgesic among the groups VAS scores at the 4th hour Preoperative rescue analgesic need (n)

Group I

Group II

4.47±1.06

3.32±0.92

<0.01

0.05

VAS scores during positioning

5.55±1.77

4.02±1.80

<0.01

VAS scores at postop 1st hour

3.30±1.06

3.12±1.09

0.47

VAS scores at postop 4th hour

3.22±1.12

3.45±0.71

0.28

VAS scores at postop12 hour

3.17±0.74

3.07±0.79

0.56

VAS scores at postop 24th hour

3.12±0.72

2.82±0.67

0.06

VAS: Visual Analogue Scale.

Table 3. Number of patients with delirium among groups and IL-6, IL-8 levels in CSF samples Delirium

Group I

Group II

9 (20.0%)

5 (10.9%)

0.227

Interleukin levels-6

3.30±1.57

3.12±1.44

0.57

Interleukin levels-8

73.15±73.35

43.23±38.52

0.017

Interleukin levels-8 (with delirium)

0.1885±0.13

0.111±0.025

0.213

Interleukin levels-6 (with delirium)

2.29±1.10

3.14±0.57

0.213

IL: Interleukin levels; CSF: Cerebrospinal fluid.

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ter pain control than paracetamol did. Similar to our study, Ranjit et al.[19] compared the effects of FNB and intravenous fentanyl administration on patients with a femur fracture. They assessed the pain during positioning for spinal anesthesia and reported that pain was significantly lower in the FNB group. Delirium is one of the most common postoperative complications in elderly patients with an incidence of 5% and 61% after femur fracture surgery.[20] The underlying pathophysiology is not fully understood; however, postoperative pain is believed to trigger delirium development in elderly patients. Morrison et al.[13] assessed 541 patients with a femur fracture. They found the incidence of delirium 16% and reported that severe pain was highly associated with the development of postoperative delirium. Moreover, adequate pain control starting from the early preoperative period was previously shown to reduce the postoperative delirium incidence.[21] In our study, preoperative pain scores were significantly lower in the cyclic FNB group. Although the postoperative delirium incidence was lower in the FNB group, the difference between groups was not statistically significant. We believe that there are two main reasons for this result. First, we maintained effective pain control as early as possible in both groups. Second, we implemented a “delirium prevention program” to all patients starting from the admittance to emergency service. “Delirium prevention program” is a list of recommendations stated by Björkelund et al.[11] It was reported to reduce the incidence of postoperative delirium from 34% to 22%. In our study, the delirium incidence was 20.0% in the paracetamol group and only 10.9% in the FNB group. Central nervous system inflammation that arises from systemic inflammation is another blamed hypothesis for delirium development after femur fracture. Previously, IL-6 and IL-8 were reported to be higher in geriatric patients who developed delirium after femur fracture operation.[9,10] In the study of MacLullich et al.,[22] the increase of IL-8 levels in the CSF was reported to be associated with postoperative delirium. Similarly, elevated IL-6 level was also reported as the signature of post-stroke delirium in a recent study.[23] In the present study, IL-8 levels were found significantly lower in the FNB group. We think that the most likely reason for this result is the attenuation of the inflammatory response by effective pain management with FNB. On the other hand, we did not detect any differences in IL-6 levels between groups. Similar to our results, Lemstra et al.[24] did not find any association between preoperative IL-6 and the incidence of delirium after a hip surgery. We think that the data concerning IL-6 and IL-8 are still limited and conflicting. The preoperative cognitive function level of patients are thought to play an essential role in the development of delirium.[25,26] Our results are consistent with the current literature, we detected a negative correlation between preoperative MMT scores and the incidence of delirium in the first three postoperative days. Moreover, there was a positive correlation between preoperative MMT scores and delirium scores. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Limitations Our study has some limitations: (1) Although the sample size is large enough to meet the primary outcome, our study is probably underpowered to detect a relation between the incidence of delirium and cytokine levels, or incidence of delirium and femoral nerve block. (2) The release of IL-6 and IL-8 may also be affected by other factors, such as the current metabolic condition, the usage of previous medications, the previous story of fractures and operations. Therefore, we may not be able to standardize these factors during the study period because of the comorbidities of patients. (3) Preoperative erythrocyte transfusion to some patients according to the “delirium prevention program” may affect cytokine responses.

Conclusions We found that intermittent femoral nerve block was more effective in preoperative pain management of trochanteric femur fracture and preventing pain during regional anesthesia application. Moreover, the mean IL-8 level was lower in the femoral nerve block group when compared to the paracetamol group. However, we could not find a difference in the postoperative delirium incidence between groups. Ethics Committee Approval: Approved by the local ethics committee (date: 17.05.2016, no: 2016/50). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.I.U., B.A., E.Y., S.G.D.; Design: A.I.U.; Supervision: S.G.D.; Fundings: A.I.U., B.A., E.Y., M.T., U.C., N.Y., S.G.D.; Materials: A.I.U., M.T., U.C., N.Y.; Data: A.I.U., M.T., U.C., N.Y.; Analysis: A.I.U., B.A., E.Y.; Literature search: A.I.U., B.A., U.C., N.Y.; Writing: A.I.U., B.A.; Critical revision: S.G.D. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Mouzopoulos G, Vasiliadis G, Lasanianos N, Nikolaras G, Morakis E, Kaminaris M. Fascia iliaca block prophylaxis for hip fracture patients at risk for delirium: a randomized placebo-controlled study. J Orthop Traumatol 2009;10:127−33. 2. Holdgate A, Shepherd SA, Huckson S. Patterns of analgesia for fractured neck of femur in Australian emergency departments: Original Research. EMA - Emerg Med Australas 2010;22:3−8. 3. Simpson PM, Bendall JC, Tiedemann A, Lord SR, Close JC. Provision of out-of-hospital analgesia to older fallers with suspected fractures: Above par, but opportunities for improvement exist. Acad Emerg Med 2013;20:761−8. 4. Aronsson K, Björkdahl I, Wireklint Sundström B. Prehospital emergency care for patients with suspected hip fractures after falling - older patients’ experiences. J Clin Nurs 2014;23:3115−23. 5. Juliebø V, Krogseth M, Skovlund E, Engedal K, Ranhoff AH, Wyller TB. Delirium is not associated with mortality in elderly hip fracture patients. Dement Geriatr Cogn Disord 2010;30:112−20. 6. Sciard D, Cattano D, Hussain M, Rosenstein A. Perioperative management of proximal hip fractures in the elderly: The surgeon and the anes-

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Uysal et al. Effect of early femoral nerve block on postoperative pain and delirium thesiologist. Minerva Anestesiol 2011;77:715−22. 7. Inouye SK, Westendorp RGJ, Saczynski JS. Delirium in elderly people. Lancet 2014;383:911−22. 8. Cunningham C, MacLullich AM. At the end of the psychoneuroimmunological spectrum: Delirium as a maladaptive sickness behavior response. Brain Behav Immun 2013;28:1−13. 9. van Munster BC, Korevaar JC, Zwinderman AH, Levi M, Wiersinga WJ, De Rooij SE. Time-course of cytokines during delirium in elderly patients with hip fractures. J Am Geriatr Soc 2008;56:1704−9. 10. de Rooij SE, van Munster BC, Korevaar JC, Levi M. Cytokines and acute phase response in delirium. J Psychosom Res 2007;62:521−5. 11. Björkelund KB, Hommel A, Thorngren KG, Gustafson L, Larsson S, Lundberg D. Reducing delirium in elderly patients with hip fracture: A multi-factorial intervention study. Acta Anaesthesiol Scand 2010;54:678−88. 12. Ritcey B, Pageau P, Woo MY, Perry JJ. Regional nerve blocks for hip and femoral neck fractures in the emergency department: A systematic review. Can J Emerg Med 2016;18:37−47. 13. Morrison RS, Magaziner J, Gilbert M, Koval KJ, McLaughlin MA, Orosz G, et al. Relationship between pain and opioid analgesics on the development of delirium following hip fracture. J Gerontol A Biol Sci Med Sci 2003;58:76−81. 14. Cryer B, Barnett MA, Wagner J, Wilcox CM. Overuse and Misperceptions of Nonsteroidal Anti-inflammatory Drugs in the United States. Am J Med Sci 2016;352:472−80. 15. Nie H, Yang YX, Wang Y, Liu Y, Zhao B, Luan B. Effects of continuous fascia iliaca compartment blocks for postoperative analgesia in patients with hip fracture. Pain Res Manag 2015;20:210−2. 16. Castillón P, Veloso M, Gómez O, Salvador J, Bartra A, Anglés F. Fascia iliaca block for pain control in hip fracture patients. [Article İn English, Spanish] Rev Esp Cir Ortop Traumatol 2017;61:383−9. 17. Arsoy D, Gardner MJ, Amanatullah DF, Huddleston JI 3rd, Goodman SB, Maloney WJ, et al. Continuous femoral nerve catheters decrease opi-

oid-related side effects and increase home disposition rates among geriatric hip fracture patients. J Orthop Trauma 2017;31:186−9. 18. Kassam AM, Gough AT, Davies J, Yarlagadda R. Can we reduce morphine use in elderly, proximal femoral fracture patients using a fascia iliac block? Geriatr Nurs 2018;39:84−7. 19. Ranjit S, Pradhan BB. Ultrasound guided femoral nerve block to provide analgesia for positioning patients with femur fracture before subarachnoid block: Comparison with intravenous fentanyl. Kathmandu Univ Med J 2016;14:125−9. 20. Robertson BD, Robertson TJ. Postoperative delirium after hip fracture. J Bone Joint Surg Am 2006;88:2060−8. 21. Hamrick I, Meyer F. Perioperative management of delirium and dementia in the geriatric surgical patient. Langenbeck’s Arch Surg 2013;398:947−55. 22. MacLullich AMJ, Edelshain BT, Hall RJ, de Vries A, Howie SEM, Pearson A, et al. Cerebrospinal fluid interleukin-8 levels are higher in hip fracture patients with peri-operative delirium versus controls. JAGS 2015;59:1151–3. 23. Kowalska K, Klimiec E, Weglarczyk K, Pera J, Slowik A, Siedlar M, et al. Reduced ex vivo release of pro-inflammatory cytokines and elevated plasma interleukin-6 are inflammatory signatures of post-stroke delirium. J Neuroinflammation 2018;15:111. 24. Lemstra AW, Kalisvaart KJ, Vreeswijk R, van Gool WA, Eikelenboom P. Pre-operative inflammatory markers and the risk of postoperative delirium in elderly patients. Int J Geriatr Psychiatry 2008;23:943–8. 25. MacLullich AMJ, Ferguson KJ, Miller T, de Rooij SEJA, Cunningham C. Unravelling the pathophysiology of delirium: A focus on the role of aberrant stress responses. J Psychosom Res 2008;65:229−38. 26. Adogwa O, Elsamadicy AA, Vuong VD, Fialkoff J, Cheng J, Karikari IO, et al. Association between baseline cognitive impairment and postoperative delirium in elderly patients undergoing surgery for adult spinal deformity. J Neurosurg Spine 2018;28:103−8.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Trokanterik femur kırığı operasyonu geçirecek yaşlı hastada erken dönemde yapılan femoral sinir blokajının ağrı yönetimi ve deliryum insidansına etkisi: Randomize kontrollü çalışma Dr. Ali İhsan Uysal,1 Dr. Başak Altıparmak,4 Dr. Eylem Yaşar,1 Dr. Mustafa Turan,4 Dr. Umut Canbek,2 Dr. Nigar Yılmaz,3 Dr. Semra Gümüş Demirbilek4 Muğla Sıtkı Koçman Üniversitesi Eğitim Araştırma Hastanesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Muğla Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Muğla Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Muğla 4 Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Muğla 1 2 3

AMAÇ: Kalça kırığı yaşlı hastalarda şiddetli ağrıya neden olan yaygın bir klinik problemdir. Bununla birlikte kırık oluşumunu takip eden şiddetli ağrı mental rahatsızlıklar ve deliryum gelişimine neden olabilir. IL-6 ve IL-8 ile birlikte olan nöroinflamatuvar yanıtın deliryum patofizyolojisi ile ilişkili olduğu gösterilmiştir. Bu çalışmadaki primer hipotezimiz ameliyat öncesi femoral sinir bloğunun trokanterik femur kırıklarında parasetamole göre daha etkin ağrı tedavisi sağlayacağıdır. Sekonder hipotezimiz IL-6 ve IL-8 düzeylerinin femoral sinir bloğu yapılanlarda daha düşük olacağıdır. Üçüncü hipotezimiz ise ameliyat sonrası deliryum insidansının femoral sinir bloğu uygulananlarda düşük olma durumudur. GEREÇ VE YÖNTEM: Hastane acil servisine femur kırığı nedeniyle başvuran 65 yaş üzeri ASA II-IV hastalar çalışmaya dahil edildi. “Deliryum önleme tablosu”ndaki öneriler tüm hastalara başvuru anından itibaren uygulandı. İlk gruba sekiz saatte bir 15 mg/kg parasetamol intravenöz olarak verildi. İkinci gruba femoral sinir blokajı uygulandı ve kateter yerleştirildi. Ardından 0.5 mL/kg bupivakain %0.25 her sekiz saatte bir kateter yoluyla verildi. Her iki grupta ağrı skorları ilk analjezik uygulandıktan dört saat sonra kaydedildi. Bütün hastlar 48 saat içerisinde spinal anestezi altında ameliyat edildi. Spinal anestezi sırasında verilen pozisyona bağlı ağrı skorları kaydedildi ve 2 mL beyin omurilik sıvısı (BOS) örneği tüm hastalardan IL-6 ve IL-8 sitokinleri analizi için alındı. BULGULAR: Ameliyat öncesi ilk ağrı tedavisi sonrası dördüncü saatteki ve rejyonal anestezi için verilen pozisyon ağrısı belirgin olarak femoral sinir blok grubunda düşüktü. IL-8 düzeyleri femoral sinir blok grubunda belirgin olarak düşük iken IL-6 düzeyleri benzerdi. Deliryum insidansı femoral sinir blok grubunda daha azken istatistiksel farklılık yoktu. TARTIŞMA: Femoral sinir bloğu ameliyat öncesi ağrı tedavisinde ve rejyonal anestezi sırasındaki pozisyon ağrısını önlemede üstündür. Ortalama IL-8 düzeyi femoral sinir blokajı uygulanan hastalarda daha düşüktür. Deliryum insidansı her iki grupta benzerdir. Anahtar sözcükler: Deliryum; femoral sinir bloğu; interlökin 8; kalça kırığı. Ulus Travma Acil Cerrahi Derg 2020;26(1):109-114

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doi: 10.14744/tjtes.2019.78002

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ORIGIN A L A R T IC L E

Factors predicting reoperation after hand flexor tendon repair Aslı Çalışkan Uçkun, M.D.,1 Fatma Gül Yurdakul, M.D.,1 Hasan Murat Ergani, M.D.,2 Tuba Güler, M.D.,1 Burak Yaşar, M.D.,3 Bedriye Başkan, M.D.,1 Hatice Bodur, M.D.,1 Ramazan Erkin Ünlü, M.D.3 1

Department of Physical Medicine and Rehabilitation, Ankara City Hospital, Ankara-Turkey

Department of Plastic and Reconstructive Surgery, Çankırı Public Government Hospital, Çankırı-Turkey

Department of Plastic and Reconstructive Surgery, Ankara City Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: This single-center, retrospective study aims to analyze the sociodemographic, injury characteristics, and the total number of lost working days of patients undergoing hand flexor tendon repair and to identify factors predicting reoperation. METHODS: Hand flexor tendon repairs conducted using a four-strand modified Kessler core suture with early rehabilitation from January 2013 to December 2016 were included in this study. The variables evaluated in this study were patient sociodemographic and injury characteristics, number of lost working days, and reoperations because of rupture and/or adhesion formation. Injury severity was determined using Modified Hand Injury Severity Scoring (MHISS). Binary logistic regression analysis was conducted to identify the predictors of reoperation. RESULTS: A total of 194 patients were included in this study, who had experienced 329 tendon injuries. Participants were young (mean age, 31.8), mostly male (79.4%), and mostly blue-collar workers (50.0%). Most patients had a zone 2 injury affecting a single digit of the dominant hand. The mean MHISS value was 46.6, and the mean time to return to work was 114.0 days. A total of 37 (19.1%) patients required reoperation because of rupture and/or adhesion formation. Smoking, zone 2 injury, and high MHISS value were negative predictors of reoperation. CONCLUSION: To minimize the need for reoperation, surgeons and rehabilitation teams should take special care of patients with zone 2 injuries, high MHISS values, and smoking history. Keywords: Flexor tendon repair; hand; outcome; reoperations; return to work; trauma.

INTRODUCTION The outcomes following flexor tendon repair of a finger are sometimes suboptimal, despite proper management, including the appropriate surgical method and rehabilitation program, and further surgery may be required.[1,2] The average reoperation rate is approximately 6% but can be as high as 20% or more.[3,4] Rupture and adhesion formation following an initial repair are two common reasons for reoperation. [5] Secondary surgery produces a higher economic burden,

which comprises the direct cost associated with treatment and the indirect cost of lost working days.[6] In addition to the economic burden of secondary surgeries on the health-care system, they generally have less favorable results than primary surgeries.[7,8] Therefore, a better understanding of the variables that may contribute to the need for reoperation is helpful in predicting the risks of poor outcomes and determining their proper management. Several individual, injury, and work-related factors, such as smoking, concomitant injuries, the zone of injury, mechanism of injury, and age, in addition

Cite this article as: Çalışkan Uçkun A, Yurdakul FG, Ergani HM, Güler T, Yaşar B, Başkan B, et al. Factors predicting reoperation after hand flexor tendon repair. Ulus Travma Acil Cerrahi Derg 2020;26:115-122. Address for correspondence: Aslı Çalışkan Uçkun, M.D. Ankara Şehir Hastanesi, Fiziksel Tıp ve Rehabilitasyon Kliniği, Ankara, Turkey Tel: +90 312 - 552 60 00 E-mail: draslical@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):115-122 DOI: 10.14744/tjtes.2019.92590 Submitted: 01.10.2019 Accepted: 08.11.2019 Online: 30.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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to the surgery and rehabilitation program, may be associated with poor outcomes and reoperation. However, many potential factors seem to have inconsistent and even contradictory associations with complications and reoperations.[2,7–11] The aims of this study were to identify the sociodemographic and injury characteristics of patients who underwent primary flexor tendon repair with a four-strand modified Kessler core suture and received early rehabilitation and to determine the prevalence of and risk factors for reoperation because of rupture and/or adhesion formation. In addition, this study aimed to compare the total number of lost working days among patients with and without reoperations, to evaluate whether reoperation resulted in more lost working days and, consequently, a higher indirect economic burden.

MATERIALS AND METHODS This study was approved by the local ethics committee of Ankara Numune Training and Research Hospital (date: 12.07.2017, no: E-17-1441).

Study Design A retrospective study was conducted, which included patients who were treated for flexor tendon injuries from January 2013 to December 2016. All patients who underwent flexor tendon repair and rehabilitation by an experienced surgical and rehabilitation team, and who had at least a 12-month follow-up, were identified from medical records. Inclusion criteria were defined as having primary flexor tendon injury repair using a four-strand modified Kessler core suture and early rehabilitation (combined Kleinert and Duran protocols).[4] Exclusion criteria were rheumatoid arthritis, severe comorbidities that were expected to have an extensive influence on time off work, extensor tendon repair, associated phalangeal fractures or nerve injuries, incomplete data, amputations, replantation and bilateral injuries, non-adherence to treatment, or age below 16 years. Patients were also excluded from this study if they had complications other than rupture or adhesion formation, but not if they had associated digital nerve and unilateral digital vessel injuries.

the nature of injury, mechanism of injury, hand dominance, side of the injured hand, number of involved digits and tendons, severity of injury, concomitant digital nerve injury, timing of surgery, zone of injury, distribution of fingers and tendons affected, and number of lost working days based on formal documentation in patient records. Data about the nature of injury were grouped into work-related injury, traffic accidents, suicide, assault, and unspecified reasons based on the formal records. Data pertaining to the mechanism of injury were categorized into either the crush group, which included saw, fan, lathe, and crush mechanisms, or the sharp group, which included glass, knives, metal, and broken porcelain mechanisms. The Modified Hand Injury Severity Score (MHISS) was used to evaluate the severity of the injury.[12] Patient medical notes of the injury that were recorded upon arrival at the emergency room, and those of the findings during surgery, were reviewed. These notes were translated into scores using the MHISS system, which assesses four domains of the forearm, wrist, and hand anatomies, including integument (nail and skin), skeletal (bone and ligament), motor (tendon), and neurovascular (vascular and nerve). Each injured structure was assigned an absolute value, which was weighted according to functional importance. The MHISS value was classified as minor (<20), moderate (21–50), severe (51–100), or major (>101).

Surgical Technique All flexor tendon repairs were carried out under general anesthesia or an axillary block using a four-strand modified

Assessments Sociodemographic characteristics were recorded from patient files and included age at injury, gender, occupation, employment type, smoking status, drug abuse history, and comorbidities. Data on occupation status were categorized into the blue-collar (laborers, production, tradespeople, and transport workers), white-collar (professionals, service, clerical, and sales workers), and non-employment groups. Economically inactive patients, such as students, housewives, or retired individuals, were classified into the non-employment group. The employment type was categorized into two further groups (self-employed or employee). The clinical and injury characteristics included in this study were 116

Figure 1. Flexor tendon repair with a four-strand modified Kessler suture technique.

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Kessler technique with 3.0 polypropylene (Fig. 1). The core repair was strengthened using a running circumferential suture with 6.0 polypropylene. In all cases, both the flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS), or the flexor pollicis longus (FPL), were repaired and the pulleys A2, A3, and A4 were preserved or repaired. All digital nerve and arterial injuries were repaired using a standard microsurgical technique with 9.0 polypropylene.

Postoperative Rehabilitation Protocol After surgery, a forearm splint was applied with the wrist in 10°–30° flexion, metacarpophalangeal joints in 50°–80° flexion, and interphalangeal joints in full extension. Rehabilitation combining “controlled passive motion” and “passive flexion and active extension” protocols” were used (combined Kleinert and Duran protocols). All patients commenced finger motion on postoperative day 3, regardless of digital nerve repairs, and received regular visits that were scheduled at least 1–2 times per week. During the first three weeks of the postoperative period, patients were instructed to perform 10 each of active extension, passive flexion, and controlled passive extension exercises of the interphalangeal joint. After the sutures were removed, the incision zone was massaged. Active finger hook flexion and fist formation in the splint were commenced at the end of week 3. Active wrist exercises were added to the program at the end of week four. The splint was removed at the end of week six but was used when sleeping or outdoors for an additional two weeks. After week eight, progressive strengthening exercises commenced. Edema control and scar massage were continued as needed.

Outcome Assessment Our aim was to identify factors associated with complications of flexor tendon injury that necessitated reoperation. Participants requiring secondary surgery (re-repair, tenolysis, and tenolysis with re-repair) because of rupture and/or adhesion formation that arises from the primary tendon repair were recorded. The number, type, and timing of reoperations were described.

set at p<0.05.

RESULTS

Patient Sociodemographic Characteristics A total of 821 patients who underwent primary flexor tendon repair were identified in this study. After exclusion criteria were applied, 329 digits were included from 194 patients with an age range of 16.0 to 72.0 years (mean, 31.8 years). A detailed flowchart of patients included in the study is provided in Fig. 2. Overall, 153 patients dropped out of the follow-up rehabilitation without specifying a reason; their characteristics were similar to the other patients, except for MHISS values, which were significantly lower (mean, 29.9, range, 11–93; p<0.001). Overall, 154 (79.4%) patients were male. Regarding the occupation status, 97 (50.0%) patients were blue-collar workers, nine (4.6%) were white-collar workers, and 88 (45.4%) were unemployed; among the workers, 27 (25%) were self-employed. Overall, 97 (50.0%) patients were current smokers, six (3.1%) patients were drug abusers, 32 (16.4%) patients had at least one comorbid diagnosis, five (2.5%) patients had at least two comorbid diagnoses, and 6 (3.1%) patients had diabetes mellitus.

Injury Characteristics The causes of injury were work-related accidents among 34 patients, assaults among 12 patients, suicide attempts among two patients, and traffic accidents among one patient. Overall, 147 patients were categorized into the sharp injury mechanism group, and most were injured by glass objects (n=88, 45.3%), followed by knives (n=54, 27.8%). The dominant hand was affected in 98 patients (50.5%). Single- or multiple-digit injuries occurred in 116 and 78 patients, respectively. The mean number of involved tendons was 2.33 (range, 1–8), and the mean MHISS value was 46.6 (range, 11–100). Minor, moderate, and severe injuries occurred in 20, 105, and 69 Primary flexor tendon repair (2013-2016)

Statistics Sociodemographic and injury characteristics were reported using descriptive statistics (mean, standard deviation, range, number, and percentage). The Shapiro–Wilk test was used to evaluate the normality of the data distribution. The Mann– Whitney U test, Student’s t-test, and Chi-squared or Fisher’s exact test were used to compare continuous or nominal variables between groups, as appropriate. Variables that were at least moderately associated with reoperation in univariate analysis (MHISS value, current smoker, zone 2 injury, and work-related injury) were selected and assessed using binary logistic regression analysis. Analyses were performed using IBM SPSS version 21.0 software (IBM Corporation, Armonk, NY, USA). Statistical significance was Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

(n=821)

Not-induded (n=627) Concomitant amputations, replantation (n=98) Concomitant bone or nerve injury (n=132) Bilateral injuries (n=25) Under 16 years of age (n=51) Participants with insufficient documentation (n=168) Quitting the treatment (n=153)

Included (n=194)

Figure 2. A detailed flowchart of patients.

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patients, respectively. Overall, 54 (27.8%) patients had unilateral or bilateral digital nerve injuries. The mean time period between injury and repair was 2.68 days (range, 1–26 days); 83 patients underwent repair on the day of injury (Table 1).

The overall rate of reoperation was 19.1% (n=37). Re-repair, tenolysis and combined tenolysis with re-repair were performed in 32.4% (n=12), 51.4% (n=19), and 16.2% (n=6) of reoperations, respectively, after a mean of 27.4 days (range, 2–60), 124.9 days (range, 60–365), and 69.8 days (range, 30– 104) following the primary tendon repair, respectively. A total of nine patients (24%) had at least two reoperations after the primary repair.

Group Comparisons Data on the number of lost working days were available from the formal documentation of only 79 patient records. The mean time to return to work was 114.0 days (range, 10–400) overall, and was significantly higher among the patients who underwent reoperation (mean, 189.0; range, 20–400) compared with the patients who did not (mean, 86.8; range, 10– 365; p<0.001, Fig. 3).

* 300

Working days lost

Zone 2 injuries were most common (58.2%), followed by zone 5 (20.1%), zone 1 (9.3%), zone 3 (7.7%), and zone 4 (4.6%). The little finger was most frequently affected (83 patients, 27.3%), followed by the middle finger (77 patients, 25.4%). Injuries affected only the FPL in 48 digits, only the FDS tendon in 42 digits, only the FDP tendon in 98 digits, and a combination of the latter two tendons in 141 digits.

400

200

100

0 Reoperation group

No reoperation group

Figure 3. Comparison of time to return to work between the group with reoperation and with no reoperation. Box limits indicate the 25th and 75th quartile, and the whiskers show the maximum and minimum scores. The line within boxes is the median. Circle and star indicate outlier data.

Patients who underwent reoperation were more likely to be current smokers, have higher MHISS values and have zone 2 injuries than the patients who did not. Data reflecting the nature of the injury were categorized into ‘‘work-related’’ and ‘‘non-work related’’ based on formal records because there were inadequate numbers to perform Chi-squared tests. Work-related injuries were significantly more common among patients who underwent reoperation (32.4%) compared with the patients who did not (14.0%; p=0.008). There

Table 1. Group comparisons of the sociodemographic and injury characteristics

No reoperation

Reoperation

Total

Age (years), mean±SD

34.3±13.9

31.7±13.1

31.8±13.3

0.210

Female gender, n (%)

35 (22.6)

5 (12.5)

40 (20.6)

0.235

Occupation 0.593 White-collar workers, n (%)

7 (4.5)

2 (5.4)

9 (4.6)

Blue-collar workers, n (%)

76 (48.4)

21 (56.8)

97 (50.0)

Unemployed, n (%)

74 (47.1)

14 (37.8)

88 (45.4)

Current smoker, n (%)

71 (45.2)

26 (70.3)

97 (50.0)

0.021*

6 (3.8)

0 (0)

6 (3.1)

0.227

Drug abuse history, n (%) Comorbidity, n (%)

26 (16.6)

6 (16.2)

32 (16.5)

0.960

Work-related injury, n (%)

22 (14.0)

12 (32.4)

34 (17.5)

0.008*

Sharp mechanism of injury, n (%)

26 (70.3)

121 (77.1)

147 (75.8)

0.385

Dominant hand injury, n (%)

76 (48.4)

22 (59.5)

98 (50.5)

0.226

MHISS value, mean±SD

44.0±22.0

57.3±23.6

46.6±22.9

0.001*

Digital nerve injury, n (%)

40 (25.5)

14 (37.8)

54 (27.8)

0.131

Timing of surgery (days after injury), mean±SD Zone 2 injury, n (%)

2.8±4.9

1.9±2.4

2.6±4.5

0.927

79 (50.3)

32 (86.5)

113 (58.2)

0.002*

MHISS: Modified Hand Injury Scoring System; SD: Standard deviation.

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Table 2. Logistic regression analysis to identify factors that predicted reoperation Independent variables

Beta

Standard error

Exp(B)

Reoperation group (n=37) Constant

4.891

0.781

133.148

<0.001

Current smoker

-1.020

0.431

0.361

0.018

Modified Hand Injury Scoring System value

-0.027

0.009

0.974

0.003

Zone 2 injury

-1.908

0.531

0.148

<0.001

Work-related injury

-0.774

0.477

0.461

0.105

Exp(B): Odds ratio.

were no significant differences between the two groups concerning age, gender, occupation, drug abuse history, comorbidity, mechanism of injury, dominant hand injury, concomitant digital nerve injury, or timing of surgery (Table 1). The binary logistic regression analysis demonstrated that higher MHISS values, smoking, and zone 2 injuries were associated with reoperation (Table 2).

DISCUSSION Rupture and adhesion formation after flexor tendon repair remain challenging complications despite developments in surgical techniques and postoperative rehabilitation protocols. The sociodemographic and injury data reported in this study were mostly similar to others; however, the 19.1% rate of reoperation was higher than previous reports in general. Patients who underwent reoperation had a significantly longer time off work compared with the patients who did not. The logistic regression analysis demonstrated that smoking, zone 2 injuries, and high MHISS values had significant and independent negative impacts on reoperation. The work-related injury was univariately associated with reoperation but did not significantly contribute to the regression model. Moreover, age, the timing of surgery, comorbidity, and presence of digital nerve injury, which had previously been found to affect the risk of reoperation, did not differ between groups.[6] Consistent with the previous studies, the findings obtained in this study demonstrated that most of the patients with flexor tendon injuries were young (mean age, 31.8), male (79.4%), and blue-collar workers (50.0%).[13,14] Proper injury management to optimize the long-term functional outcomes and economic burden are important among patients with these characteristics, who potentially have a prolonged working life expectancy requiring adequate hand function.[15] The rate of work-related injuries based on formal records in our study was 17.5%, which was markedly lower than that reported in previous studies.[13,16] Hand injuries frequently occur when performing a manual task at home or, in particular, at work. [13,17] The reason for our low rate of work-related injuries may be a lack of available formal records, which may be explained by various legal or economic challenges, and the unavailability Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

of patient self-reported data. These records must be very strictly maintained to enable the application of sanctions to employers and prevent future work-related accidents. We found that the dominant hand (50.5%) was affected somewhat more often than the non-dominant hand, which was similar to the findings reported by Thangavelu et al.,[14] although other studies reported similar or less frequent rates.[13,17,18] The dominant hand is usually injured when using a sharp object directly or catching a falling object. The non-dominant hand provides support when performing tasks, such as using a knife or saw, and is often injured while assisting the dominant hand. Therefore, the different rates of injury to either hand across studies are not surprising because patients with different mechanisms of injury were included. Similar to previous studies, zone 2 injuries (58.2%) were most common, which is probably because this is the longest zone, which had tendons confined to a narrow area and no protective tissues.[13] The second most frequently affected zone was 5 (20.1%). We found that little and middle fingers were injured the most. The index or little finger in zone 2 is most injury prone, whereas, in zone 5, injury is more likely to affect the middle finger.[19] Our findings supported the association between affected zones and fingers. Combined FDS and FDP injuries were most common in our study, followed by isolated FDP injuries, then isolated FDS injuries. These findings, which are generally compatible with the existing literature, can be explained because the FDP tendon is more superficial in zone 2, which is the longest and most injured zone, and zone 1 only contains the FDP tendon.[13,20] The overall reoperation rate in our study was 19.1%, which is generally higher than previous reports.[6,21] Patients who dropped out of the follow-up rehabilitation had lower MHISS values; therefore, these patients would be more likely to have good functional results or only small residual functional deficits with little follow-up required. This situation may have presumably resulted in bias leading to the overestimation of the reoperation rate. 119

Çalışkan Uçkun et al. Factors predicting reoperation after hand flexor tendon repair

The mean time to return to work was 114.0 days, based on the formal records for 79 patients, which was higher than previous studies.[22,23] Only the patients who had available data reflecting their time off work from National Health Insurance records in our country were evaluated. Our findings may be explained by the substantial number of blue-collar workers (87.3%) included, who have been found to return to work later than white-collar workers and the patients who are selfemployed.[24] Blue-collar workers engage in more manual labor compared with white-collar workers and receive greater disability benefits through insurance compared with self-employed patients, which may reduce their ability to return to work. Consistent with previous studies, the time off work was significantly higher in the reoperation group.[17] Therefore, to reduce time off work and the overall cost of health insurance, it is necessary to determine the factors affecting reoperation. Various sociodemographic, injury, psychosocial, and economic factors, as well as surgical and rehabilitation protocols, may be associated with the occurrence of complications and the need for reoperation after flexor tendon repair.[6,25] However, as a result of the limitations of our dataset, we focused our evaluation on the effects of sociodemographic and injury characteristics on reoperation in patients who underwent similar surgical and rehabilitation protocols. We found that the reoperation group had significantly higher MHISS values, smoking rates, zone 2 injuries and work-related injuries than the group who did not undergo reoperation. Logistic regression analysis demonstrated that work-related injuries did not contribute to the overall results. In the combined model, zone 2 injuries, higher MHISS values, and smoking had significant negative effects on reoperation. Zone 2 injury is a well-known risk factor for poorer outcomes.[2,7] This is related to the difficult anatomy of this zone, which includes the FDS and FDP within its narrow fibro-osseous sheath.[26] Therefore, our finding that zone 2 injury was associated with complications and reoperation compared with other zones was expected. MHISS, which indicates the initial anatomic injury severity, provides an objective and comprehensive assessment.[27] MHISS is useful for predicting the duration of lost working time,[28] functional recovery[29] and future health-related quality of life.[30] We demonstrated that it is also useful to predict reoperation. This is reasonable, as the injury severity probably increases the edema, pain, and subsequent fibrosis, leading to an increased risk of complications and associated reoperations. The relationship between hand injury severity and reoperation could be helpful for the initial identification of higher-risk patients who might benefit from additional support. The negative effects of smoking on tendon healing have been demonstrated in many studies.[2,31,32] Our results confirmed that smoking was a negative predictor of reoperation after flexor tendon repair, and was the only modifiable factor in 120

our study. A single cigarette has been implicated in reduced blood supply and volumetric flow, leading to increased vascular resistance and overall tissue hypoxia.[33] In our clinic, patients are given personal advice and encouragement to stop smoking. However, some patients do not attempt to stop smoking, which may be because they do not understand its importance, have had negative life events that reinforce smoking, or have personal traits associated with continued smoking, such as decreased self-esteem, increased depression, or maladaptive coping and health behaviors. The high rate of reoperations in smokers may be explained by these features, rather than the direct effect of smoking. Therefore, it might be more appropriate to evaluate smoking together with personal factors that affect adherence to rehabilitation. In addition to advising patients to stop smoking, the complications and associated operations could be reduced by supporting smoking cessation, for example, by providing counseling for nicotine replacement or behavioral therapy. Our study has several limitations. First, we did not evaluate functional results but only analyzed reoperation because of the data that were available. The need for reoperation is an acceptable outcome indicator, but may not be optimal. In addition, subjective and individual factors that might affect the decision to undergo reoperation could not be evaluated because of the limitations of our dataset. Finally, data were obtained from a single center; therefore, it is difficult to generalize our results. Our study has some strengths. We included patients who underwent surgery and rehabilitation by the same experienced team in a single-center, thereby eliminating confounding variables related to the surgical technique or rehabilitation protocol. We also measured the number of lost working days based on formal records rather than self-reported data, which prevented bias.[34] In addition, the severity of the injury was measured using the MHISS, which is an objective assessment that is designed specifically for hand injuries. A higher severity injury score was correlated strongly with higher functional impairment.[28,29]

Conclusion Zone 2 injuries, high MHISS values, and smoking were predictors of reoperation after primary flexor tendon repair. However, zone 2 injuries and high MHISS values cannot be modified, and can only be used as predictive indicators for the initial selection of patients who should be followed-up closely and managed comprehensively. However, the complications and associated operations can be reduced by supporting smoking cessation. In routine practice, many extra approaches, rather than just advice for stopping smoking, may lead to more positive results. Ethics Committee Approval: Approved by the local ethics committee (date: 12.07.2017, no: E-17-1441). Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Çalışkan Uçkun et al. Factors predicting reoperation after hand flexor tendon repair

Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.Ç.U., H.M.E., B.Y., B.B., R.E.Ü.; Design: A.Ç.U., H.M.E., B.Y., B.B., R.E.Ü.; Supervision: H.B., R.E.Ü.; Materials: A.Ç.U., H.M.E., T.G., B.Y., H.B.; Data: A.Ç.U., H.M.E., T.G., B.Y., H.B.; Analysis: F.G.Y., T.G., B.Y., B.B.; Literature search: A.Ç.U., F.G.Y., T.G., H.B.; Writing: A.Ç.U., F.G.Y., T.G., H.B.; Critical revision: H.B., R.E.Ü. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Sikora S, Lai M, Arneja JS. Pediatric flexor tendon injuries: A 10-year outcome analysis. Can J Plast Surg 2013;21:181−5. 2. Rigo IZ, Røkkum M. Predictors of outcome after primary flexor tendon repair in zone 1, 2 and 3. J Hand Surg Eur Vol 2016;41:793−801. 3. Tang JB. Flexor tendon repair in zone 2C. J Hand Surg Br 1994;19:72−5. 4. Chesney A, Chauhan A, Kattan A, Farrokhyar F, Thoma A. Systematic review of flexor tendon rehabilitation protocols in zone II of the hand. Plast Reconstr Surg 2011;127:1583−92. 5. Dy CJ, Hernandez-Soria A, Ma Y, Roberts TR, Daluiski A. Complications after flexor tendon repair: a systematic review and meta-analysis. J Hand Surg Am 2012;37:543−51. 6. Dy CJ, Daluiski A, Do HT, Hernandez-Soria A, Marx R, Lyman S. The epidemiology of reoperation after flexor tendon repair. J Hand Surg Am 2012;37:919−24. 7. Elliot D, Giesen T. Treatment of unfavourable results of flexor tendon surgery: Ruptured repairs, tethered repairs and pulley incompetence. Indian J Plast Surg 2013;46:458−71. 8. Pulos N, Bozentka DJ. Management of complications of flexor tendon injuries. Hand Clin 2015;31:293−9. 9. Edsfeldt S, Eklund M, Wiig M. Prognostic factors for digital range of motion after intrasynovial flexor tendon injury and repair: Long-term follow-up on 273 patients treated with active extension-passive flexion with rubber bands. J Hand Ther 2019;32:328−33. 10. Starnes T, Saunders RJ, Means KR Jr. Clinical outcomes of zone II flexor tendon repair depending on mechanism of injury. J Hand Surg Am 2012;37:2532−40. 11. Fujihara Y, Ota H, Watanabe K. Utility of early active motion for flexor tendon repair with concomitant injuries: A multivariate analysis. Injury 2018;49:2248−51. 12. Urso-Baiarda F, Lyons RA, Laing JH, Brophy S, Wareham K, Camp D. A prospective evaluation of the Modified Hand Injury Severity Score in predicting return to work. Int J Surg 2008;6:45−50. 13. Chang MK, Tay SC. Flexor Tendon Injuries and Repairs: A Single Centre Experience. J Hand Surg Asian Pac Vol 2018;23:487−95. 14. Thangavelu M, Veerasamy N, Kanthan A. Study on evaluation and management of hand injuries. J Evolution Med Dent Sci 2016;5:4703−6. 15. Marom BS, Ratzon NZ, Carel RS, Sharabi M. Return-to-Work Barriers Among Manual Workers After Hand Injuries: 1-Year Follow-up Cohort Study. Arch Phys Med Rehabil 2019;100:422−32. 16. Savvidou C, Tsai TM. Clinical Results of Flexor Tendon Repair in Zone II Using a six Strand Double Loop Technique. J Hand Microsurg

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2015;7:25−9. 17. Ramel E, Rosberg HE, Dahlin LB, Cederlund RI. Return to work after a serious hand injury. Work 2013;44:459−69. 18. Kaskutas V, Powell R. The impact of flexor tendon rehabilitation restrictions on individuals’ independence with daily activities: implications for hand therapists. J Hand Ther 2013;26:22–8. 19. Khor WS, Langer MF, Wong R, Zhou R, Peck F, Wong JK. Improving Outcomes in Tendon Repair: A Critical Look at the Evidence for Flexor Tendon Repair and Rehabilitation. Plast Reconstr Surg 2016;138:1045−58. 20. Rosberg HE, Carlsson KS, Höjgård S, Lindgren B, Lundborg G, Dahlin LB. What Determines the Costs of Repair and Rehabilitation of Flexor Tendon Injuries in Zone II? A Multiple Regression Analysis of Data From Southern Sweden. J Hand Surg Br 2003;28:106−12. 21. Hsiao PC, Yang SY, Ho CH, Chou W, Lu SR. The benefit of early rehabilitation following tendon repair of the hand: A population-based claims database analysis. J Hand Ther 2015;28:20−5. 22. Oberfeld E, Zwahlen M, Vögelin E. Return to work after traumatic hand injuries: medical, personal and work-related factors. [Article in German] Handchir Mikrochir Plast Chir 2015;47:44−57. 23. Eisele A, Dereskewitz C, Kus S, Oberhauser C, Rudolf KD, Coenen M; Consortium Lighthouse Project Hand. Factors affecting time off work in patients with traumatic hand injuries-A bio-psycho-social perspective. Injury 2018;49:1822−9. 24. Opsteegh L, Reinders-Messelink HA, Schollier D, Groothoff JW, Postema K, Dijkstra PU, et al. Determinants of return to work in patients with hand disorders and hand injuries. J Occup Rehabil 2009;19:245–55. 25. Lewis D. Tendon rehabilitation: factors affecting outcomes and current concepts. Current orthopaedic practice 2018;29:100−4. 26. Hurley CM, Reilly F, Callaghan S, Baig MN. Negative Predictors of Outcomes of Flexor Tendon Repairs. Cureus 2019;11:4303. 27. Campbell DA, Kay SP. The hand injury severity scoring system. J Hand Surg 1996;21:295–8. 28. Çakır N, Özcan RH, Kitiş A, Büker N. Investigation of the relationship between severity of injury, return to work, impairment, and activity participation in hand and forearm injuries. Ulus Travma Acil Cerrahi Derg 2014;20:120−6. 29. Mink van der Molen AB, Ettema AM, Hovius SE. Outcome of hand trauma: the hand injury severity scoring system (HISS) and subsequent impairment and disability. J Hand Surg Br 2003;28:295−9. 30. Chang JH, Shieh SJ, Kuo LC, Lee YL. The initial anatomical severity in patients with hand injuries predicts future health-related quality of life. J Trauma 2011;71:1352−8. 31. Samona J, Samona S, Gilin M, Persons S, AG Dass. Effects of Smoking on Hand Tendon Repair: Scientific Study & Literature Review. Int J Surg Res 2017;4:70−4. 32. Trumble TE, Vedder NB, Seiler JG 3rd, Hanel DP, Diao E, Pettrone S. Zone-II flexor tendon repair: a randomized prospective trial of active place-andhold therapy compared with passive motion therapy. J Bone Joint Surg Am 2010;92:1381−9. 33. Lee JJ, Patel R, Biermann JS, Dougherty PJ. The musculoskeletal effects of cigarette smoking. J Bone Joint Surg Am 2013;95:850−9. 34. van Poppel MNM, de Vet HCW, Koes BW, Smid T, Bouter LM. Measuring sick leave: a comparison of self-reported data on sick leave and data from company records. Occup Med 2002;52:485−90.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

El fleksör tendon onarımı sonrası reoperasyonu öngören faktörler Dr. Aslı Çalışkan Uçkun,1 Dr. Fatma Gül Yurdakul,1 Dr. Hasan Murat Ergani,2 Dr. Tuba Güler,1 Dr. Burak Yaşar,3 Dr. Bedriye Başkan,1 Dr. Hatice Bodur,1 Dr. Ramazan Erkin Ünlü3 1 2 3

Ankara Şehir Hastanesi, Fiziksel Tıp ve Rehabilitasyon Anabilim Dalı, Ankara Çankırı Devlet Hastanesi, Plastik ve Rekonstrüktif Cerrahi Anabilim Dalı, Çankırı Ankara Şehir Hastanesi, Plastik ve Rekonstrüktif Cerrahi Anabilim Dalı, Ankara

AMAÇ: Bu tek merkezli, geriye dönük çalışma, el fleksör tendon onarımı geçiren hastaların sosyodemografik, yaralanma özelliklerini ve toplam kayıp iş günlerini analiz etmeyi ve reoperasyonu öngören faktörleri tanımlamayı amaçlamaktadır. GEREÇ VE YÖNTEM: Ocak 2013–Aralık 2016 tarihleri arasında erken rehabilitasyona tabi, dört geçişli modifiye Kessler kor dikiş kullanılarak yapılan el fleksör tendon onarımları dahil edildi. Bu çalışmada değerlendirilen değişkenler; hasta sosyodemografik ve yaralanma özellikleri, kayıp iş günü sayısı ve rüptür ve/veya adezyon oluşumu nedeniyle yapılan reoperasyonlardı. Yaralanma ciddiyeti, Modifiye El Yaralanması Ciddiyet Skorlaması (MEYCS) kullanılarak belirlendi. Reoperasyonun öngörücülerini belirlemek için ikili lojistik regresyon analizi yapıldı. BULGULAR: Toplam 329 tendon yaralanması geçirmiş 194 hasta çalışmaya dahil edildi. Katılımcılar genç (ortalama yaş, 31.8), çoğunlukla erkek (%79.4) ve mavi yakalı çalışanlardı (%50.0). Hastaların çoğu dominant elin tek parmağını etkileyen zon 2 yaralanmasına sahipti. Ortalama MEYCS değeri 46.6 ve işe geri dönüş süresi 114.0 gündü. Toplam 37 (%19.1) hastaya rüptür ve/veya adezyon oluşumu nedeniyle reoperasyon gerekti. Sigara içimi, zon 2 yaralanması ve yüksek MEYCS değeri, reoperasyonun negatif belirleyicileriydi. TARTIŞMA: Reoperasyon ihtiyacını en aza indirmek için, cerrahlar ve rehabilitasyon ekibi, bölge 2 yaralanması, yüksek MEYCS değerleri ve sigara içme öyküsü olan hastalara özel dikkat göstermelidir. Anahtar sözcükler: El; fleksör tendon onarımı; işe dönüş; reoperasyonlar; sonuç; travma. Ulus Travma Acil Cerrahi Derg 2020;26(1):115-122

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ORIGIN A L A R T IC L E

Upper extremity replantation results in our series and review of replantation indications Ayhan Okumuş, M.D.,1

Aret Cerci Özkan, M.D.2

Aesthetic, Plastic and Reconstructive Surgery Office, Bursa-Turkey

Department of Emergency and First Aid, European Vocational High School, İstanbul-Turkey

ABSTRACT BACKGROUND: Upper extremity amputations are usually not life-threatening, but they negatively affect the life quality of the victim. In addition to the functional disabilities of upper extremity amputation, disfigurements frequently cause psychological and social debilitations. METHODS: Between 2007–2015, fourteen cases were admitted to emergency with total major amputation of the upper extremity. All cases were male (22–45 years of age. Mean age: 29.6). Replantation was applied to all except three cases with multileveled crush injuries. RESULTS: All replantations were successful. Additional interventions were needed in four cases with replantation at elbow level and replantation at the distal arm level. The postoperative functional results were evaluated. The patient’s overall satisfaction, the recovery of flexor and extensor mobility, the extent of the active motion of digits, the recovery of thumb opposition, active movements of wrist and elbow joints, recovery of sensitivity in the median and ulnar nerve, the ability of the surviving hand and/or forearm to perform daily works are all evaluated. The results were satisfactory in hand replantations. However, some ulnar nerve distal motor problems were encountered in three cases with replantation at elbow level, and one case with replantation at the distal arm level with a crush injury, acceptable and excellent results were obtained in other cases. CONCLUSION: Despite the availability of prostheses, cadaveric upper extremity replantations, replantation of the native extremity is still the most appropriate treatment for amputated cases. However, surgeons should realize that the ultimate goal is not merely to save the viability of the extremity through replantation, but rather to preserve the life quality by improving the function. Keywords: Arm amputation; forearm amputation; hand amputation; indication of replantation; replantation.

INTRODUCTION Upper extremity amputations are usually not life-threatening, but they negatively affect the life quality of the victim. In addition to the obvious functional sequelae of upper extremity amputation, serious disfigurements frequently imply profound psychological and social debilitations.[1] The extremely important role of the hand in body image and sense of identity, as well as in work, relationships, activities has been confirmed by many authors.[2] Disabilities experienced in the daily life of individuals having congenital or acquired upper extremity loss and their requirements to several special rehabilitation tools is a well-known reality. Hands are one of the

most crucial parts of our body in all our relationships with the external environment. Technologically powered prostheses may be satisfactory in cases with congenital absence of the upper extremity. However, it is not possible to talk about the same satisfaction in cases with acquired loss of the upper extremity. Even the best functioning prosthesis cannot be compared with a native extremity. Thus, in cases admitted to emergency clinics with amputation injuries, the best and acceptable restoration option is still the replantation of the native hand, albeit with its decreased and limited functional and sensational skills.

Cite this article as: Okumuş A, Özkan AC. Upper extremity replantation results in our series and review of replantation indications. Ulus Travma Acil Cerrahi Derg 2020;26:123-129. Address for correspondence: Ayhan Okumuş, M.D. Ihsaniye Mahallesi, İlknur Sokak, Bulvar 224 Sitesi, B: Blok, D: 10, 16120 Nilüfer, Bursa, Turkey Tel: +90 224 - 243 43 43 E-mail: ayhan@ayhanokumus.com.tr Ulus Travma Acil Cerrahi Derg 2020;26(1):123-129 DOI: 10.14744/tjtes.2019.85787 Submitted: 16.04.2019 Accepted: 23.10.2019 Online: 27.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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MATERIALS AND METHODS Between 2007 and 2015, fourteen cases were admitted to our emergency department with total major amputation of an upper extremity. All cases were male, whose ages ranged from 22 to 45 years with a mean age of 29.6 yrs. All of the amputations were work-related injuries. Three of them had severe multilevel crush injuries beginning from the shoulder level. Three of them had an amputation at the distal arm level. One of these three cases with distal arm amputation also had crush injury at the forearm and fragmented fracture of the humerus. Two of these three cases had clean-cut injuries. One of these two cases also had a partial cut injury at an axillary level without any nerve damage but with an injury to biceps, teres major and latissimus dorsi muscles (Fig. 1b). In five cases, the amputation was between elbow and wrist and four cases had hand amputation with clear cut injuries (Fig. 1ac). Replantation was applied to all of the cases except three cases having severe multilevel crush injuries beginning from the shoulder level. Either cold or warm ischemia times were appropriate in all cases. All cases admitted to an emergency clinic in three hours after injury, together with the physician practicing for that workplace. All of the amputates except one were reached to the hospital in properly prepared cold

ischemic conditions. One case was admitted without proper cooling, but the warm ischemia time was appropriate in that specific case.

Surgical Procedure and Evaluation In all cases, the preoperative preparation included prophylactic antibiotics, tetanus prophylaxis, iv. fluid supply to prevent volume loss, warming the patient to prevent hypothermia and vasoconstriction, Foley catheter application, and protection of possible decubitus areas. The exploration of the amputated part started before the patient is brought to the operating room. In most cases, there was plenty of time before the patient is transferred to the operating room for exploration of the amputated part. In all cases with hand amputation, replantation was performed under general anesthesia with a tourniquet application. After debridement, the arteries, veins, nerves, and tendons were identified and tagged in both stumps. Signs of arterial damage was noted. Only loose small bone fragments of the carpus were removed, but all of the carpal bones were saved and internal osteosynthesis was performed using two or three K-wires (size 2.2 mm. 30 cm). In one case, with fragmented humerus fracture, an external fixator was used. Repair of all amputated structures, namely all tendons and

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)

(i)

Figure 1. (a) Case-1: Wrist amputation. (b) Case 2: Distal arm amputation and axillary region soft tissue injury. (c) Case 2: Distal arm amputation. (d, e) Case 1: Early post-operative view. (f) Case 1: Post-operative 3rd year, full ekstansion of fingers. (g) Case 1: Post-operative 3rd year view, full flexion of fingers. (h) Case 2: Post-operative 5th year view, full flexion of fingers, view of biceps muscle fonction. (i) Case 1: Post-operative 5th year view, full flexion of wrist and fingers, abduction of thumb.

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l 8.5 29 Excellent Most of the daily activities L: Left; : Right; D: Dominant hand; ND: Non-dominant hand; ROM: Range of motion.

8 2 Wrist 11 (26, L, ND)

High

l 11

9 23

31 Excellent

Good Most of the daily activities

Most of the daily activities 7

10 High Mid-forearm

4 Proximal hand 9 (32, L, ND)

10 (29, L, ND)

High

ll 8

10 30

16 Fair

Excellent Most of the daily activities

Holding, gripping, pinching only 12–14

9 High 2

Wrist

Proximal forearm

7 (25, R, D)

8 (37, L, ND)

Moderate

lll 6

7 19

14 Fair

Good Most of the daily activities

Holding, gripping, pinching only 14–16

10–12 High

Moderate 3

Distal arm

Distal Forearm

5 (27, R, D)

6 (31, L, ND)

IV x x x x x Very low-and 1 Forearm 4 (24, L, ND)

Amputated

6.5 24

29 Excellent

Good Most of the daily activities

Most of the daily activities 8

10–12 High

High 1

2 Distal forearm 2 (28, L, ND)

Wrist

Axillary soft

3 (45, L, D)

l 7 22 Good Most of the daily activities 14–16 High tissue damage

The two-point discrimination test was used to measure postoperative sensibility (Table 1). The

Assessment

All preoperative, per-operative and postoperative principals were similar in replantations at elbow level except the need for fasciotomies and fixation of muscles instead of tendons. In cases with replantations at arm level, fasciotomies were performed in both flexor and extensor compartments of the forearm. In cases with replantations at the forearm level, the fasciae of both flexor and extensor compartments were released without skin release. Vessel, nerve, or tendon grafting was not applied in any of the replantation cases in our series.

Postoperatively, broad-spectrum antibiotics, low dose Heparin to prevent deep vein thromboses, Dextran RMI 10 g (500 mL/day for 3 days), analgesic drugs (Flubiprofen) were applied for all patients. The K-wires were usually removed after 7–8 weeks. Physiotherapy was started on the tenth postoperative day and continued until the sixth postoperative month. Patients were encouraged to abstain from cigarettes, coffee, and tea consumption.

Table 1. Summary of sensory and functional results of replantation

Postoperative Management

Distal arm,

In hand replantations, Both the radial and ulnar arteries and four or five of the largest dorsal veins were repaired end-to-end under a microscope by using 8/0 ethanol. Neurorrhaphy of the median and ulnar nerves were also performed primarily using an epi-perineural technique with 8–9/0 nylon. None of the cases required the use of a vein or nerve grafts. After the skin closure, the affected limb was placed in a thermoplastic splint, which included the hand and forearm, and elevated for several days.

Patient Amputation Follow-up Satisfaction No-Age level (year) level

2-Point Physical performance ROM discrimination of the daily activities (Normal <6 mm)

Grip strength (kgf)

Pinch strength (kgf)

In a case with additional soft tissue injury at the axillary region, all the muscles, bones and tendons at that region were also meticulously repaired after replantation. In replantations at the arm level, all the injured structures but specifically the triceps and biceps muscles were primarily repaired. At the forearm level, all the muscle repairs were executed with great care in order not to interfere with the blood circulation of the repaired vascular structures.

1 (22, L,ND)

Criteria of chen

nerves, are done after providing both arterial and venous circulation by microsurgical vascular anastomoses (Fig. 1d, e).

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Okumuş et al. Upper extremity replantation results in our series and review of replantation indications

recovery of motor activity was evaluated based on the range of motion of each joint measured by a goniometer. Additionally, the total range of motions of the replanted fingers and thumbs was compared with the normal range of motions of the undamaged side and it is reported as a percentage of normal. The range of motions were rated as excellent (76% to 100%), good (51% to 75%), fair (26% to 50%), poor (1% to 25%), and fixed (0%) based on “The Guides to the Evaluation of Permanent Impairment”.[3] The handgrips and pinch strengths were measured using a hand dynamometer and pinch meter. The Criteria of Chen was used[4] to evaluate the functional outcomes (Table 1).

RESULTS All replantations were successful. The postoperative course of all four hand replantations and five replantations at elbow level and two arm replantations in our series was uneventful in the early postoperative period. In our series, fasciotomies were not performed in any hand replantation case. Infection, compartment syndrome, soft tissue necrosis, or any vascular complication requiring reoperation were not encountered. All of the cases were followed up 3 yrs (1–12 yrs). Additional surgical interventions, namely tenolysis, muscle release, skin contracture release, and bone refixation, were needed in a case with fragmented humerus fracture and forearm arm replantation and also in other three cases with forearm replantations. Unfortunately, functional recovery has not been satisfactory in the case of humerus fracture and forearm crushed

amputation injury. He had unbearable and incremental pain and subsequent amputation was performed distal to elbow level at the fourth month of replantation with the decision of the patient. In other replantation cases, additional surgical intervention was not required (Table 2). The postoperative functional and sensory results were evaluated (Table 1). The patient’s overall satisfaction, the recovery of flexor and extensor mobility of the thumb and fingers, the degree of the active motion of each digit, the recovery of thumb opposition, active motions of wrist and elbow joints, recovery of sensitivity in the median and ulnar nerve distributions, the ability of the surviving hand, forearm or arm to perform daily tasks are all examined together with physiotherapists (Table 1). The results were highly satisfactory in four of the hand replantations and three forearm replantation (Fig. 1f-i). However, minor ulnar nerve functional losses were observed in two distal arms, one distal forearm, and one proximal forearm level replantations. There were intrinsic muscle atrophies and related functional losses in their activities (Table 2).

DISCUSSION The decision to attempt replantation of the severed part is influenced by many factors, including the importance of the part, level of injury, expected return of function, and mechanism of injury. Hand amputation through palm, hand amputation at distal wrist, any amputated part in a child, only sharp injuries more proximal arm are indications for major replan-

Table 2. The comparison of conservatively and surgically managed patients in grade IV Patient No-Age

Amputation Level

Replantation procedure

Secondary procedures

Results

1 (22, L, ND)

Distal arm, axillary

Primary, no greft,

Ulnar nerve distal

soft tissue damage

2 (28, L, ND)

Distal forearm

no shortening Primary

3 (45, L, D) 4 (24, L, ND)

Satisfactory

Forearm

Primary

Debridement, skin graft,

Amputation

Distal arm

Primary

bone refixation Bone refixation, skin

1-5 finger flexion insuficency,

contracture release

radial and ulnar nerve distal

7 (25, R, D) 8 (37, L, ND)

motor insuficiency

Primary

6 (31, L, ND)

Ulnar nerve distal

Wrist

5 (27, R, D)

motor insuficiency

sensational insufficiency

Distal forearm

Primary

Wrist

Primary

Satisfactory

Proximal forearm

Primary

Skin contracture relase,

ulnar nerve distal

Satisfactory

motor insufficiency

9 (32, L, ND)

Proximal hand

Primary

Satisfactory

10 (29, L, ND)

Mid-forearm

Primary

Tenolysis

Satisfactory

11 (26, L, ND)

Wrist

Primary

Satisfactory

L: Left; R: Right; D: Dominant hand; ND: Non-dominant hand.

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tation. Amputations with severely crushed or mangled parts, multiple-level amputations are contraindications of a major replantation. Replantation in patients with multiple trauma or severe medical problems is a relative contraindication.[5] If an amputated forearm is exposed to hot ischemia, the limb may not be salvageable. So it is suggested that every team dealing with limb replantation should evaluate whether the amputated part is exposed to hot injury or not.[6] The significance not only of the survival of the replanted extremity but also on functional superiority compared to a revision amputation has emphasized.[7] In addition, progressive improvement in sensation is ideal. In their comparison of patients undergoing either replantation or revision amputation with a subsequent prosthesis after major upper extremity limb trauma, Graham et al.[8] observed superior functional outcomes years after injury (average, 7.3 years) in patients who underwent replantation. Further, outcomes were even better in the replanted group when the intrinsic function was recoverable. Regarding success and durability of replantation, it is claimed that ‘‘a ‘bad hand’ may be more functional than a ‘good amputation’ in the upper extremity’’.[9] The factors related to good outcomes after replantation include the potential for long-term function, the patient’s overall clinical status (including psychosocial wellbeing), the mechanism of injury, and the location of the injury. Specifically, better outcomes at 1 to 2 years have been observed in patients experiencing guillotine-type injuries near the level of the carpus. Similar long-term results were observed by Sugun et al.,[10] where avulsion or crush amputations near the elbow, as opposed to the wrist, were associated with a worse prognosis. Presence of satisfactory results in distal level replantations, and presence of ulnar nerve motor and sensational problems in proximal level amputations in our series, parallel with the results of Sugun et al. However, it is interesting to note that, in the case with a clean-cut distal arm amputation, all the motor, and sensorial functions were regained except some degree of intrinsic muscle functions of the hand after replantation. In this specific case, we believe that his young age (22 yrs.), his confidence for a total recovery in the near future, his positive psychosocial mood were all helped him and of course, his good discipline in attending to all physiotherapy sessions was also highly effective in obtaining highly satisfactory results. Good functional results can be achieved with replantation of injuries at the level of the hand at the wrist, and the upper extremity at the distal forearm. Replantation of the above elbow amputation should be attempted for elbow preservation, even though the chance for nerve recovery is low. If subsequent nerve regeneration is inadequate after upper arm replantation, revision amputation at the mid-forearm level can then allow for a below the elbow prosthesis. A below elbow prosthesis with a gravity activated grip is more functional than an above elbow prosthesis.[11] Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

It may be an unrealistic expectation to successfully replant severely crushed and mangled body parts. Avulsion injuries with traction along the neurovascular bundles create intimal tears and disruption of small branches to the skin. Small hematomas seen in the skin along the course of the neurovascular bundle result in the ‘‘red line sign.’’ This sign signifies such detrimental injury to the neurovascular bundle that replantation is often fraught with poor success.[11] Two other relative contraindications to replantation include multiplelevel injuries and mentally unstable patients. Even if not replantable, this amputated part can provide a valuable tissue source for reconstruction. The amputated part should be wrapped in a saline-moistened gauze sponge and placed in a plastic bag. The plastic bag should be sealed and placed on ice. The amputated part should not be placed directly on ice because this can result in a frostbite injury to the tissue.[12] The part should not be immersed in water. The recommended ischemia times for reliable success with replantation are 12 hours of warm and 24 hours of cold ischemia for digits, and 6 hours of warm and 12 hours of cold ischemia for major replants. Delayed and suspended replantations demonstrate results comparable to immediate replantation regarding graft survival and clinical outcome.[13] In our series, any delay in cold or warm ischemia time or in hospitalization and operation processes did not happen. In replantaions at the arm level, brachial artery and vein, ulnar median and radial nerves are repaired with the written order. The muscles should be repaired unless they do not apply compression over anastomosed vascular structures. The skin should be approximated loosely. Skin grafts may be used if necessary. Especially in high-level amputations, some degree of muscle debridement sessions may be necessary with 48 hrs intervals. Arm level amputations may usually disturb biceps muscle functions and may necessitate pectoralis or latissimus muscle transfers. Skin grafting was not required in any of our eleven amputation cases. In two cases with arm-level amputation, muscles are repaired primarily without any related complication. In a case having multiple muscular injuries at the axillary level, the primary repair of these muscles did not cause any contracture, adhesion, or muscular atrophy. Despite the presence of both proximal and distal injuries of biceps muscle any postoperative problem is not encountered. Replantation of hand amputations at the wrist level may sometimes necessitate bone shortening (e.g., proximal row corpectomy) to avoid nerve and vein grafts. Overall, the ulnar and radial arteries, four veins, median, ulnar, and superficial radial nerves are repaired and many tendons as possible. At least the four flexor digitorum profundus tendons, flexor carpi radialis, flexor carpi ulnaris, four extensor digiti communis tendons, extensor carpi ulnaris, extensor carpi radialis, extensor pollicis longus, and flexor pollicis longus should be performed. In general, replantations at this level can achieve very good results. In all of our cases, the brachial artery at 127

Okumuş et al. Upper extremity replantation results in our series and review of replantation indications

arm level or radial and ulnar artery and all ınjured nerves, muscles and tendons are repaired. The repair of flexor digitorum superficialis tendons is not spared during operation in our series. These are also totally repaired in all cases. At postoperative recovery, warming the patient’s room to avoid vasospasm, positioning the extremity at the heart level to minimize edema but not compromise arterial or venous flow is done. Anticoagulation is generally recommended. Sympathetic blocks have been described for high-risk replantations after crush avulsion injuries. Arterial insufficiency is the most common cause of replantation failure, accounting for approximately 60% of failures. Treatment of arterial insufficiency includes removal of potentially constricting dressings and tight sutures, decreasing extremity elevation to promote inflow with gravity, and sympathetic blockade. Finally, an early operative intervention can be considered if there is no improvement with the above measures. Reexploration to correct arterial insufficiency has been reported to be successful in 50% of return visits.[14,15] Venous congestion is a less common cause of replantation failure.[14,15] Venous congestion should be suspected with rapid capillary refill increased tissue turgor or bleeding of wound edges. Reexploration sequences for venous problems are similar to reexploration of arterial insufficiencies. As the Chen classification[4] prepared for the postoperative evaluation of the cases with replantation of upper extremity assesses resuming the original work or another gainful work, performing daily activities, the range of motion at the affected joint and the recovery of sensibility, it is possible to use this classification to assess the success of the replantation in all cases having different amputation levels. That is why this classification is preferred in our series having amputations at different levels. Developing technology with more sophisticated microscopes, new systems, such as spy fluorescent imaging,[16] more delicate micro-instruments, and gradually increasing the experience of microsurgeons, make it real to obtain more satisfactory results compared to the past. Obtaining very satisfactory functional recoveries even at high-level amputations by virtue of these developments encourage microsurgeons to expand the formerly established rigid criteria[5] of classical indications for replantation especially in young patients with clean-cut amputations because every individual successful replantation result thoroughly saves the wellness of one human’s life and even the wellness of one family.

Conclusion Despite the presence of high-tech prostheses and replantation possibilities from cadavers, replantation of the native extremity is still the best and optimum treatment for amputated patients, but this does not mean that all amputated parts should be replanted regardless of the condition and the level 128

of the amputation. Clean cut injuries may lead to amplifying the surgeon’s judgment toward replantation even in proximal levels as results of our series imply. Conclusively, surgeons should recognize that the ultimate goal is not merely to preserve all living tissue through nonselective replantation, but rather to preserve the quality of life by improving function and, secondarily, appearance.[17] Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.O, A.C.Ö.; Design: A.O, A.C.Ö.; Supervision: A.O, A.C.Ö.; Materials: A.O; Data: A.O, A.C.Ö.; Analysis: A.O, A.C.Ö.; Literature search: A.O, A.C.Ö.; Writing: A.O, A.C.Ö.; Critical revision: A.O, A.C.Ö. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Poore SO, Israel JS, Rao VK. Thirty-year follow-up of total hand replantation: A case report. Ann Plast Surg 2016;76:521−3. 2. Hoang NT. Hand replantations following complete amputations at the wrist joint: first experiences in Hanoi, Vietnam. J Hand Surg Br 2006;31:9−17. 3. Committee on rating of mental and physical impairment: the extremities and back. In: Rondinelli RD, editor. Guides to the Evaluation of Permanent Impairment. Chicago, IL: American Medical Association; 1971. p. 1−13. 4. Chen ZW, Meyer VE, Kleinert HE, Beasley RW. Present indications and contra-indications for replantation. In: Watson HK, Weinzweig J, editors. The Wrist. 1st ed. New York, NY: Lippincott Williams & Wilkins; 2000. p. 269−76. 5. Pederson WC. Replantation. Plast Reconstr Surg 2001;107:823−41. 6. Coban YK. Failure of replantation of middle forearm amputation exposed to hot environment. Microsurgery 2013;33:418−9. 7. Tark KC, Kim YW, Lee YH, Lew JD. Replantation and revascularization of hands: clinical analysis and functional results of 261 cases. J Hand Surg Am 1989;14:17−27. 8. Graham B, Adkins P, Tsai TM, Firrel J, Breidenbach WC. Major replantation versus revision amputation and prosthetic fitting in the upper extremity: a late functional outcomes study. J Hand Surg Am 1998;23:783−91. 9. Tintle SM, Baechler MF, Nanos GP 3rd, Forsberg JA, Potter BK. Traumatic and trauma-related amputations: Part II: Upper extremity and future directions. J Bone Joint Surg Am 2010;92:2934−45. 10. Sugun TS, Ozaksar K, Ada S, Kul F, Ozerkan F, Kaplan I, et al. Longterm results of major upper extremity replantations. Acta Orthop Traumatol Turc 2009;43:206−13. 11. Wilhelmi BJ, Lee WP, Pagenstert GI, May JW Jr. Replantation in the mutilated hand. Hand Clin 2003;19:89−120. 12. Hayhurst JW, O’Brien BM, Ishida H, Baxter TJ. Experimental digital replantation after prolonged cooling. Hand 1974;6:134−41. 13. Woo SH, Cheon HJ, Kim YW, Kang DH, Nam HJ. Delayed and suspended replantation for complete amputation of digits and hands. J Hand Surg Am 2015;40:883−9. 14. O’Brien B. Replantation surgery. Clin Plast Surg 1974;1:405−26.

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Okumuş et al. Upper extremity replantation results in our series and review of replantation indications 15. O’Brien B, Miller GD. Digital reattachment and revascularization. J Bone Joint Surg Am 1973;55:714−23. 16. Brooks D. Perfusion Assessment with the SPY System after Arterial Venous Reversal for Upper Extremity Ischemia. Plast Reconstr Surg Glob

Open 2014;2:185. 17. Bastidas N, Cassidy L, Hoffman L, Sharma S. A single-institution experience of hand surgery litigation in a major replantation center. Plast Reconstr Surg 2011;127:284−92.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Üst ekstremite majör replantayon sonuçlarımız ve endikasyonların tekrar gözden geçirilmesi Dr. Ayhan Okumuş,1 Dr. Aret Cerci Özkan2 1 2

Ayhan Okumuş Estetik, Plastik ve Rekonstrüktif Cerrahi Ofisi, Bursa Avrupa Meslek Lisesi Acil ve İlk Yardım Bölümü, İstanbul

AMAÇ: İş ile ilgili el amputasyonları tek başlarına hayatı tehdit edici değildir. Ancak fonksiyonel sekellerine ek olarak oluşturduğu sosyal ve pikolojik sorunlar kişinin yaşam kalitesini olumsuz yönde etkiler. GEREÇ VE YÖNTEM: 2007–2015 yılları arasında, 14 kişi üst ekstremite majör ampütasyonu ile acile başvurdu. Tüm olgular erkekti (ortalama 29.6 [22–45] yaş). Çok seviyeli ezilme yaralanması olan üç olgu hariç 11 olguya replantasyon uygulandı. BULGULAR: Tüm replantasyonlarda başarı sağlandı. Önkol seviyesinden replantasyon yapılan iki ve distal kol seviyesinden replantasyon yapılan bir olguya ameliyat sonrası ek girişimler uygulandı. Ameliyat sonrası fonksiyonel sonuçlar değerlendirildi. Hastanın genel memnuniyeti, fleksör ve ekstansör hareket seviyeleri, her parmağın aktif hareket derecesi, başparmak opozisyon derecesi, el bileği ve dirsek eklemlerinin aktif hareketleri, medyan ve ulnar sinir traselerinde duyusal iyileşmesinın sonuçları, replante edilen elin ve/veya önkolun tüm günlük görevleri yerine getirebilirliği incelendi. Sonuçlar, el replantasyonlarında tatminkardı, ancak, proksimal önkol ve distal kol seviyesinde replantasyon yapılan dört olguda özellikle unlar sinir fonksiyonlarında distal motor minör fonksiyon sekelleri ile karşılaşıldı. Diğer hastalarda mükemmele yakın sonuçlar alındı. TARTIŞMA: Gelişmiş protez seçenekleri, kadavralardan replantasyon olanaklarına rağmen, doğal ekstremitenin replantasyonu, ampute hastalar için hala en uygun tedavi yöntemidir. Bununla birlikte cerrahlar, nihai amacın sadece canlı dokuyu replante etmek değil, fonksiyon ve görünümü iyileştirerek yaşam kalitesini korumak olduğunu kabul etmelidir. Anahtar sözcükler: El amputasyonu; kol amputasyonu; önkol amputasyonu; replantasyon, replantasyon edikasyonu. Ulus Travma Acil Cerrahi Derg 2020;26(1):123-129

doi: 10.14744/tjtes.2019.85787

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CAS E SERI ES

Mid-term results of displaced acetabulum fractures surgically treated using anterior intra-pelvic approach (modified Stoppa) Ömür Çağlar, M.D.,1 Saygın Kamacı, M.D.,1 Şenol Bekmez, M.D.,2 Ahmet Mazhar Tokgözoğlu, M.D.,1 Bülent Atilla, M.D.,1 Emre Acaroğlu, M.D.3 1

Department of Orthopaedic Surgery, Hacettepe University Faculty of Medicine, Ankara-Turkey

Department of Orthopaedic Surgery, Çankaya Hospital, Ankara-Turkey

Department of Orthopaedic Surgery, Memorial Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: This study aims to evaluate the radiological and clinical mid-term results of the patients with displaced acetabular fractures surgically treated with open reduction and internal fixation using an anterior intra-pelvic approach (AIP). METHODS: In this study, we retrospectively reviewed 12 patients with displaced acetabular fractures treated surgically via the AIP approach. Patients were analyzed for Letournel’s acetabular fracture classification, associated injuries, time to surgery, additional surgical procedures needed, perioperative and postoperative complications, radiologic and functional results. RESULTS: Of the 12 patients, the male/female ratio was 1/2; the mean age was 40.5±16.2 (16–64) years. The mean follow-up time was 59.8±32.2 (12–124) months. Seven patients had both column fractures, three patients had anterior column + posterior hemitransverse fractures, one patient had transverse + posterior wall and one patient had anterior column fracture. The mean time to surgery was 6.6±4.4 (2–16) days. The mean intraoperative blood transfusion was 830 (300–2000) ml. Intra-operative and post-operative complications were noted in eight patients. The mean Merle d’Aubigné and Postel score was 14.5±2.7 (10–18). Six patients with an anatomical reduction of the fracture showed excellent/good functional and radiologic outcomes. Three patients with a non-anatomic reduction developed post-traumatic arthrosis that was treated with total hip arthroplasty. CONCLUSION: AIP approach provides a satisfactory exposure for the surgical treatment of displaced anterior wall/column and both column acetabular fractures. Clinical outcome is directly related to the reduction quality. Patients with poor reduction are most likely to develop mid-term complications, such as hip joint arthrosis. Keywords: Acetabulum fracture; anterior column; anterior intra-pelvic approach; anterior wall; both column; modified Stoppa approach.

INTRODUCTION The aims for the treatment of acetabular fractures are to restore the normal anatomy, prevent secondary arthrosis and gain the pre-injury functional levels. The reduction quality is of paramount importance for satisfactory clinical outcomes. [1] The ilioinguinal approach was widely used for the surgical treatment of the anterior column and both column fractures. However, exploration and retraction of the femoral artery,

vein and nerve may cause potential catastrophic complications. Iatrogenic injury of these structures and compression symptoms that arise from fibrosis around the inguinal canal may occur.[2–5] The recent trend is towards using the anterior intra-pelvic approach (AIP), which is the modification of the Stoppa approach with an additional lateral iliac wing window. Stoppa approach was first described in 1975 by Rene Stoppa[6] for inguinal hernia repair surgery. Later in 1994, Cole et al.[7] published the modification of the Stoppa approach (AIP) for

Cite this article as: Çağlar Ö, Kamacı S, Bekmez Ş, Tokgözoğlu AM, Atilla B, Acaroğlu E. Mid-term results of displaced acetabulum fractures surgically treated using anterior intra-pelvic approach (modified Stoppa). Ulus Travma Acil Cerrahi Derg 2020;26:130-136. Address for correspondence: Saygın Kamacı, M.D. Hacettepe Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatolji Anabilim Dalı, Ankara, Turkey Tel: +90 312 - 305 50 00 E-mail: sayginkamaci@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):130-136 DOI: 10.14744/tjtes.2019.03835 Submitted: 02.05.2018 Accepted: 25.02.2019 Online: 02.01.2020 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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acetabular fracture surgery. AIP approach provides direct exposure to pubis, posterior surface of the pubic ramus, quadrilateral surface, infra-pectineal surface, sciatic notch and anterior sacroiliac joint.[8] AIP approach has advantages over the ilioinguinal approach. AIP necessitates less surgical exposure and possibly decreases the risk of infection, bleeding and heterotopic ossification. Avoiding the use of the second window of the inguinal approach decreases the risk of femoral bundle injuries. Technically, AIP allows the reduction of superomedial roof impaction and medial to lateral reduction maneuvers of `central dislocations. Visualization of vital structures allows safe and effective reduction of clamp positioning. Additionally, it allows the utilization of plating configurations and screw trajectories not possible with an extrapelvic approach or difficult through the ilioinguinal approach. AIP approach facilitates a safe anterior approach for the patients with prior inguinal hernia repair.[8,9] This study aims to identify the usefulness of the AIP approach for open reduction and internal fixation of acetabular frac-

tures and demonstrate our mid-term clinical results both radiologically and functionally.

MATERIALS AND METHODS We retrospectively reviewed 115 patients with displaced acetabular fractures surgically treated at our institution by staff trauma team between the years of 2003–2012. Patients with isolated posterior wall and/or column fractures surgically treated using the Kocher-Langenbeck approach, patients with anterior wall and/or column fractures treated using the ilioinguinal approach and patients treated with percutaneous fixation were excluded from this study. Twelve patients who were surgically treated with open reduction and internal fixation using AIP approach were included in this study. Preoperative radiographs and computerized tomography images were analyzed by two separate trauma surgeons and a third observer included when there was a disagreement between the two observers (Fig. 1). Fracture types were classified according to the Leteournel classification.[1,2] Patients were evaluated for associated injuries, time to surgery, the need

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)

(i)

Figure 1. 25 years-old female, motor vehicle accident. A-P pelvis (a) and Judet views (b, c). Preoperative computerized tomography scan shows both column fracture (d–f). Post-operative x-ray (g) and computerized tomography scan (h, i) show anatomical restoration of fracture.

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Table 1. Reduction criteria for acetabular fractures described by Matta et al.

Table 3. Merle d’ Aubigne and Postel criteria Criteria Score

Displacement

Reduction quality

<1 millimeter

Anatomical

Pain None

2–3 millimeters

Imperfect

Slight or intermittent

>3 millimeters

Poor

After walking but resolves

Table 2. Matta radiological criteria at follow-up Radiographic appearance • Normal appearance of the hip

Excellent Good

sclerosis • Intermediate changes, moderate osteophytes • Moderate (<50%) narrowing of joint and

Fair

moderate sclerosis • Advanced changes, large osteophytes • Severe (>50%) narrowing of the joint, collapse or

Poor

wear of the femoral head, and acetabular wear

for additional surgeries, perioperative complications, radiographic and functional outcomes. Reduction quality was assessed by Matta’s acetabular fracture reduction criteria (Table 1). Matta’s radiological classification system was used to assess post-operative osteoarthritis (Table 2). “Merle d’Aubigné and Postel scoring system” was used to determine functional results (Table 3).

Surgical Technique The patient is positioned in the supine position on a radiolucent table; anterior-posterior and Judet pelvis radiographs are obtained. Antibiotic prophylaxis is done 20 minutes before skin incision. Ipsilateral hip and knee are flexed to release tension over iliopsoas muscle and external iliac vessels. A Foley catheter is placed to observe the urine output and protect the bladder from iatrogenic injury. A transverse “Pfannenstiel” skin incision is done 2 cm proximal to the pubic symphysis. Skin and subcutaneous tissue are incised, and rectus fascia is incised parallel to the rectus muscle fibers. Transversals fascia is opened just proximal to the pubic symphysis. Superficial dissection lateral to the rectus abdominis is avoided to prevent iatrogenic injury to spermatic cord inguinal ligament. Retzius’ space is bluntly exposed, packed with laparotomy sponges, and the bladder is retracted. Then, subperiosteally dissection is performed from the posterior pubis and advanced to the iliac fossa. A Hohmann retractor is placed over the pubic tubercle and rectus abdominis is retracted. External iliac vessels and iliopsoas are protected 132

Moderately severe but the patient is able to walk

Severe, prevents walking

Walking Result

• Mild changes, small osteophytes • Moderate (1 mm) narrowing of joint & minimum

Normal

No cane but slight limp

Long-distance with cane/crutch

Limited even with support

Very limited

Unable to walk

Range of motion 95–100%

80–94%

70–79%

60–69%

50–59%

<50%

Clinical grade Excellent

Good

15–17

Fair

13–14

Poor

<13

and retracted by a Deaver retractor. “Corona-mortis”, the anastomoses between external iliac and obturator arteries, located over the superior pubic ramus, is ligated and dissection is advanced to quadrilateral surface. Iliopectineal fascia is elevated over the anterior column, and the exposure is expanded to the anterior sacroiliac joint. A retractor is placed on the sciatic notch to protect and retract obturator neurovascular structures. A lateral traction pin is placed to the femoral head to ease the reduction and release the tension over the obturator neurovascular structures. The lateral window of the ilioinguinal approach is used, especially for anterior column reduction.

RESULTS The patients’ age, associated injuries, acetabular fracture types according to Letournel’s classification, the amount of blood transfused, the need for additional surgeries, perioperative complications, the quality of reduction, follow-up times, radiological and functional scores at the final follow-up were demonstrated in Table 4. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Both column

Anterior column 7

6 Aort aneurism

Liver laceration 1500

500

600

Imperfect

Anatomic

Fair

Poor

Excellent

Superficial

Arthrosis

–

Blood Follow-up Reduction Radiologic Functional Complications transfusion. time quality score score (ml) (months)

No support but

Total hip replacement

Normal walking

Functional ability

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Both column

posterior hemitransverse

Anterior column +

800

Anatomic

Good

Decubitus ulcer

Proximal humerus

700

Anatomic

Excellent

–

pelvic fracture

Vertically unstable

Both column

posterior hemitransverse

Anterior column +

600

124

Imperfect

Fair

–

400

Anatomic

Excellent

Sciatic nerve

fracture

Tibia diaphysis

Both column

posterior hemitransverse

Anterior column +

Both column

–

fracture

Frontal bone

–

2000

1000

300

Imperfect

Poor

Anatomic

Good

Poor

Excellent

Transverse +

posterior wall

Both column

11 5

3 Hip dislocation

Aort aneurism

600

1000

Poor

Anatomic

Poor

Excellent

Arthrosis

Incisional hernia

vein injury

Intra-op iliac

Arthrosis

–

irritation

Total hip replacement

Normal walking

with a cane

Short distance

Total hip replacement

Normal walking

with a cane

Short distance

limping

No support but

limping

No support but

fracture

wound infection limping

humeral amputation

Traumatic mid-

Time to Associated surgery injuries (day)

Patient Age Fracture no (years) type

Table 4. Summary of results in the study group

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The female/male ratio was 1/2. The mean age was 40±16 (16– 64) years. The mean time for fracture fixation surgery was 6.6±4.4 (2–16) days. The mean intraoperative blood transfusion was 830 (300–2000) ml. The surgical treatment was performed using a combined AIP + Kocher-Langenbeck approach in one patient with a transverse + posterior wall fracture-dislocation. Although AIP alone is sufficient exposure for both columnar fractures, an additional posterior approach (Kocher-Langenbeck) was added to the surgery to address posterior wall fracture-dislocation. The patient was placed in a lateral decubitus position, and posterior wall fracture was treated using the KocherLangenbeck approach than the patient flipped to the supine position, and the AIP approach was performed with open reduction and internal fixation of the transverse fracture at the same surgery. The mean follow-up time was 59.8±32.2 (12–124) months, and the mean Merle d’Aubigné and Postel scores were 14.5±2.7 (10–18) at the final follow-up. Complications were noted in eight patients. Iliac vein injury that arose from retraction occurred in one patient that was primarily repaired intra-operatively. Superficial wound infection occurred in one patient that was treated with intra-venous antibiotics. One patient had an incisional hernia, and one patient had a decubitus ulcer. One patient suffered from sciatic nerve irritation symptoms due to implants. This patient went on sciatic nerve exploration, and implants were partially removed on the 26th months post-operatively. One patient with associated hip dislocation and two patients with poor reduction developed post-traumatic hip arthrosis and undergone total hip replacement surgery.

DISCUSSION The goals of the treatment of displaced and unstable acetabular fractures are to avoid post-operative arthrosis and gain pre-injury functional activity level. Thus, open reduction and internal fixation are indicated in this type of fractures. [2] Letournel and Judet’s acetabular fracture classification system, based on the anatomic configuration of the fracture, is most widely used.[1] Various surgical approaches have been identified for the surgical treatment of acetabular fractures regarding the anatomic configuration of the fracture. Generally, the Kocher-Langenbeck approach was used for the surgical treatment of posterior wall and/or column fractures, and the ilioinguinal approach was used for the anterior wall and/or column fractures.[3–5] However, the recent trend for the surgical treatment of anterior wall/column, both column fractures involving the quadrilateral surface, is towards using the AIP approach for open reduction and internal fixation. Cole et al.[7] published successful outcomes on 55 patients with displaced isolated anterior wall/column or both column fractures treated with open reduction and internal fixation using AIP. AIP approach is indicated for anterior wall/column fractures, anterior column + posterior hemitransverse 134

fractures, both column fractures, transverse fractures and fractures of the quadrilateral surface associated with medial dislocation of the femoral head.[10–12] In our series, seven patients had both columns, three patients had anterior column + posterior hemitransverse, one patient had transverse + posterior wall, and one patient had isolated anterior column fractures. AIP approach is contraindicated for the patients with a history of cesarean-section, prostate, uterus, or bladder surgery because of the high risk of bladder injury and bleeding.[8,12] In a cadaver study Kacra et al.[9] identified that obturator vessels and iliolumbar vessels are primarily at risk during the AIP approach. The presence of an inguinal hernia or previous hernia surgery is not considered as a contraindication for the AIP approach. The main advantages of AIP approach are direct visualization of entire pelvic brim from pubic body to anterior aspect of sacroiliac joint and ease of implant placement to the quadrilateral surface, direct visualization and access to the posterior column from the greater sciatic notch to the ischial spine allowing for reduction and plating, protection of femoral neurovascular bundle and spermatic cord thus lower risk for neurovascular injury and shorter surgical time.[12–14] In a prospective randomized study comparing AIP and ilioinguinal approaches, Shazar et al.[15] demonstrated that the AIP approach showed better reduction quality. The complication rates showed no statistically significant difference between the two approaches. Ma et al.[16] have stated that the AIP approach is associated with shorter surgical time and a lower need for blood transfusion. AIP approach has been recommended for acetabular fracture if an anterior approach is needed. In this series, our results were comparable with the current literature. We experienced that AIP provided excellent surgical exposure for open reduction and internal fixation of fractures of the quadrilateral surface and both column fractures. We were able to obtain an excellent or good reduction in 75% of the cases with this technique. Additionally, fracture reduction and implant placement could be obtained successfully. However, due to the heterogeneity of our patient group with different comorbidities, we could not conclude on intra-operative blood loss in this study. At the final follow-up (mean of 5 years), clinical outcome scoring using the Merle d’Aubigné and Postel system showed that 50% of the patients were rated good or excellent, and 25% of them rated moderate. These functional scores were found to be lower than the 1-year follow-up clinical scores reported in the literature with the same scoring system.[15,16] Therefore, the long term complications, such as hip joint arthrosis, occur progressively; these findings may be attributed to our longer follow-up times. Three complications related directly to the surgical approach occurred in three patients: 1 of an iliac vein injury, superficial wound infection and a direct inguinal hernia. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

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Surgical reduction quality for acetabular fracture surgery is directly related to radiological results.[17] We found that good clinical and radiological results were directly correlated with the reduction quality. All patients with an anatomical reduction showed excellent/good functional and radiological scores. Bastian et al.[18] have shown that the inability to obtain an anatomic reduction of acetabular fractures is associated with a high risk of hip joint arthrosis that needed joint replacement surgery in midterm follow-up. In our series, patients who had residual fracture displacement less than 1 mm showed better clinic and functional outcomes. Three patients with 2 mm or more residual displacement developed hip joint arthrosis and underwent joint replacement surgery. Several studies reported the outcomes of acetabular fractures treated with the AIP approach. To our knowledge, the current literature is lack of mid-term and long-term clinical results of AIP approach on anterior-sided acetabular injuries. Our results with a mean follow-up of five years are a useful addition to the literature. Therefore, we demonstrated midterm complications like hip arthrosis and implant irritation that needed surgical treatment. There are a few drawbacks of our study. Firstly, this study is a retrospective case series. Prospective randomized controlled studies are needed to come out with a stronger conclusion. Secondly, our sample size is relatively small, with 12 patients. In conclusion, the AIP approach is an effective approach for the treatment of acetabular fracture surgery when anterior exposure of acetabulum is required, especially for both column fractures. Additionally, the surgeon should be aware of mid-term complications in patients with a non-anatomical reduction like hip joint arthrosis. Informed Consent: Written informed consent was obtained from the patients for the publication of the case report and the accompanying images. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: Ö.Ç.; Design: Ö.Ç.; Supervision: E.A.; Fundings: Ö.Ç.; Materials: Ö.Ç.; Data: Ö.Ç.; Analysis: B.A.; Literature search: Ş.B.; Writing: S.K., Ş.B.; Critical revision: A.M.T. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

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REFERENCES 1. Matta JM, Mehne DK, Roofi R. Fractures of the acetabulum. Early results of a prospective study. Clin Orthop relat Res 1986;205:241−50. 2. Judet R, Judet J, Letournel E. Surgical treatment of recent fractures of the acetabulum: (Apropos of 46 operated cases) [Article in French]. Mem Acad Chir (Paris) 1962;88:369−77. 3. Letournel E. The treatment of acetabular fractures through the ilioinguinal approach. Clin Orthop Relat Res 1993;292:62−76. 4. Weber TG, Mast JW. The extended ilioinguinal approach for specific both column fractures. Clin Orthop Relat Res 1994;305;106−11. 5. Karunakar MA, Le TT, Bosse MJ. The modified ilioinguinal approach. J Orthop Trauma 2004;18:379−83. 6. Stoppa RE, Rives JL, Warlaumont CR, Palot JP, Verhaeghe PJ, Delattre JF. The use of Dacron in the repair of hernias of the groin. Surg Clin North Am 1984;64:269−85. 7. Cole JD, Bolhofner BR. Acetabular fracture fixation via a modified Stoppa limited intrapelvic approach: Description of operative technique and preliminary treatment results. Clin Orthop Relat Res 1994;305:112−23. 8. Hirvensalo E, Lindahl J, Kiljunen V. Modified and new approaches for pelvic and acetabular surgery. Injury 2007;38:431−41. 9. Kacra BK, Arazi M, Cicekcibasi AE, Büyükmumcu M, Demirci S. Modified medial Stoppa approach for acetabular fractures: an anatomic study. J Trauma 2011;71:1340−4. 10. Ponsen KJ, Joosse P, Schigt A, Goslings JC, Goslings CJ, Luitse JS. Internal fracture fixation using the Stoppa approach in pelvic ring and acetabular fractures: technical aspects and operative results. J Trauma 2006;61:662−7. 11. Qureshi AA, Archdeacon MT, Jenkins MA, Infante A, DiPasquale T, Bolhofner BR. Infrapectineal plating for acetabular fractures: A technical adjunct to internal fixation. J Orthop Trauma 2004;18:175−8. 12. Archdeacon MT, Kazemi N, Guy P, Sagi HC. The modified Stoppa approach for acetabular fracture. J Am Acad Orthop Surg 2011;19:170−5. 13. Khoury A, Weill Y, Mosheiff R. The Stoppa approach for acetabular fracture. Oper Orthop Traumatol 2012;24:439−48. 14. Sagi HC, Afsari A, Dziadozs D: The anterior intra-pelvic (modified rives-stoppa) approach for fixation of acetabular fractures. J Orthop Trauma 2010;24:263−70. 15. Shazar N, Eshed I, Ackshota N, Hershkovich O, Khazanov A, Herman A. Comparison of acetabular fracture reduction quality by the ilioinguinal or the anterior intrapelvic (modified Rives-Stoppa) surgical approaches. J Orthop Trauma 2014;28:313−9. 16. Ma K, Luan F, Wang X, Ao Y, Liang Y, Fang Y, et al. Randomized, controlled trial of the modified Stoppa versus the ilioinguinal approach for acetabular fractures. Orthopedics 2013;36:e1307−15. 17. Matta JM. Fractures of the acetabulum: accuracy of reduction and clinical results in patients managed operatively within three weeks after the injury. J Bone Joint Surg Am 1996;78:1632−45. 18. Bastian JD, Tannast M, Siebenrock KA, Keel MJ. Mid-term results in relation to age and analysis of predictive factors after fixation of acetabular fractures using the modified Stoppa approach. Injury 2013;44:1793−8.

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OLGU SERİSİ - ÖZET OLGU SUNUMU

Anteriyor intra-pelvik yaklaşımla (modifiye Stoppa) tedavi edilen deplase asetabulum kırıklarının orta dönem sonuçları Dr. Ömür Çağlar,1 Dr. Saygın Kamacı,1 Dr. Şenol Bekmez,2 Dr. Ahmet Mazhar Tokgözoğlu,1 Dr. Bülent Atilla,1 Dr. Emre Acaroğlu3 1 2 3

Hacettepe Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatolji Anabilim Dalı, Ankara Çankaya Hastanesi, Ortopedi ve Travmatoloji Kliniği, Ankara Memorial Hastanesi, Ortopedi ve Travmatoloji Kliniği, Ankara

AMAÇ: Bu çalışmanın amacı deplase asetubulum kırıklarının cerrahi tedavisinde anteriyor-intra pelvik (AİP) yaklaşımla açık redüksiyon ve içten tespitin etkinliğini, orta dönem klinik ve radyolojik sonuçlarını ortaya koymaktır. GEREÇ VE YÖNTEM: Deplase asetabulum kırığı tanısıyla başvuran hastalardan AİP yaklaşım ile açık yerleştirme ve içten tespit uygulanan 12 hasta geriye dönük olarak incelendi. Hastalar, kırık tipi, ek yaralanma varlığı, ameliyata kadar geçen süre, ek cerrahi girişim ihtiyacı, perioperatif komplikasyonlar, radyografik ve fonksiyonel sonuçlar açısından değerlendirildi. BULGULAR: Erkek/kadın oranı 1/2 idi. Ortalama yaş 40.5±16.2 (16-64) yıldı. Ortalama takip süresi 59.8±32.2 (12–124) aydı. Yedi hastada çift kolon, üç hastada anteriyor kolon+posteriyor hemitransvers, bir hastada transvers+posterior duvar ve bir hastada anteriyor kolon kırık paterni mevcuttu. Hastalar, ortalama 6.6±4.4’üncü (2–16) günde ameliyat edildi. Amaliyat sırasında kan transfüzyonu ortalama 830 (300–2000) mL idi. Sekiz hastada ameliyatta ve ameliyat sonrası komplikasyonlar gözlemlendi. Ortalama Merle d’Aubigné and Postel skoru 14.5±2.7 (10–18) idi. Anatomik redüksiyon elde edilen altı olguda mükemmel/iyi fonksiyonel ve radyolojik sonuç gözlemlendi. Anatomik olmayan redüksiyon elde edilen üç hastada orta dönemde post-travmatik kalça artrozu gelişti ve total kalça replasmanı ile tedavi edildi. TARTIŞMA: AİP yaklaşım, asetabulumun deplase anteriyor duvar/kolon ve özellikle çift kolon kırıklarının cerrahi tedavisinde yeterli açılımı sağlar. Klinik sonuçlar, redüksiyon kalitesiyle doğrudan ilişkilidir. Anatomik olmayan redüksiyon elde edilen hastalarda orta-dönemde kalça eklem artrozu açısından dikkatli olunmalıdır. Anahtar sözcükler: Anterior duvar; anterior intra-pelvik yaklaşım; anteriyor kolon; asetabulum kırığı; çift kolon; modifiye Stoppa. Ulus Travma Acil Cerrahi Derg 2020;26(1):130-136

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doi: 10.14744/tjtes.2019.03835

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CAS E SERI ES

Long-term comparative study of internal fixation with Kirschner wires or cannulated screws for displaced medial epicondyle fractures of the humerus in children: A 10-year follow-up of 42 cases Ömer Naci Ergin, M.D., Mehmet Demirel, M.D., Serkan Bayram, M.D., Fuat Bilgili, M.D.

Fatih Şentürk, M.D.,

Department of Orthopaedics and Traumatology, İstanbul University İstanbul Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: The rationale behind the decision-making on which type of fixation to use in displaced medial epicondyle fractures is not well elucidated. This study aims to compare the long-term clinical and radiographic outcomes of internal fixation with either Kirschner wires (K-wires) or cannulated screws in children with displaced medial epicondyle fractures. METHODS: In this study, 42 consecutive children who underwent surgical treatment for medial epicondyle fractures displaced more than 5 mm were categorized into two groups as follows: group A, 22 children undergoing fixation with K-wires and group B, 20 children undergoing fixation with a screw. The mean age was nine (median, 10.5; range, 6–14) years in group A and 15 (16, 10–17) in group B. The overall follow-up was 10 (median, 10; range, 5–15) years. To assess patients’ clinical outcomes, the Mayo Elbow Performance Scores (MEPS) were used in addition to the elbow range of motion (ROM) at the last follow-up. During the radiographic assessment, possible deformities secondary to the epicondyle fracture were examined on final follow-up radiographs. RESULTS: The main MEPS were 95 (median, 95; range, 85–100) and 93 (94, 85–100) in groups A and B, respectively (p=0.18). In ROM, no significant differences were observed (p=0.43). In the radiographic assessment, one patient from each group developed a fibrous union, and one from each group had hypoplasia. There was no significant relationship between the deformity and fixation type (p=0.34, χ2 test). CONCLUSION: Two smooth K-wires for younger children and screw fixation for children near skeletal maturity may provide favorable clinical and radiological outcomes at long-term follow-up, with low morbidity and radiographic deformity. Keywords: Fracture fixation; Kirschner wire fixation; medial epicondyle humerus fracture; pediatric elbow fracture; screw fixation.

INTRODUCTION Although medial epicondyle fractures of the humerus constitute approximately 12% of all pediatric elbow fractures, the literature is controversial regarding the management of these pediatric fractures.[1] The disagreement lies particularly in identifying the suitable treatment method for children with considerable displacement (>5 mm). Traditional knowledge

suggests that displaced medial epicondyle fractures can be nonoperatively treated with satisfactory outcomes despite a high rate of pseudarthrosis.[2,3] However, in recent years, there is an emerging consensus that such patients may benefit more from open reduction and internal fixation.[1,4] The most commonly used methods for the fixation of displaced fractures include Kirschner wires (K-wires) in younger

Cite this article as: Ergin ÖN, Demirel M, Şentürk F, Bayram S, Bilgili F. Long-term comparative study of internal fixation with Kirschner wires or cannulated screws for displaced medial epicondyle fractures of the humerus in children: A 10-year follow-up of 42 cases. Ulus Travma Acil Cerrahi Derg 2020;26:137-143. Address for correspondence: Mehmet Demirel, M.D. İstanbul Üniversitesi İstanbul Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, 34100 İstanbul, Turkey Tel: +90 212 - 414 20 00 E-mail: dr88.mehmet.demirel@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):137-143 DOI: 10.14744/tjtes.2019.77348 Submitted: 14.11.2019 Accepted: 17.12.2019 Online: 27.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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patients with open physis and screws with or without a washer in children near skeletal maturity.[5] However, as per our literature review, the rationale behind the decision-making on which type of fixation to use in such fractures has not been well elucidated in the literature. To contribute to the relevant literature, in this study, we aim to investigate the rationale behind the decision on the type of fixation in such fractures, by comparing the long-term clinical and radiographic outcomes of surgical treatment using either K-wires or cannulated screws in children with displaced medial epicondyle fractures.

Assesing for eligibility (n=51) Exclusion criteria (n=9) • <2 years old follow-up, (3 children) • Lost to follow-up, (2) • Open fractures, (2) • Concomitant ipsilateral upper extremity fractures, (2)

Children included in the study (n=42)

MATERIALS AND METHODS After obtaining approval from the institutional review board, 51 consecutive patients who underwent open reduction and internal fixation for the treatment of displaced fracture of the medial humeral epicondyle from 2003 to 2013 were retrospectively reviewed in this study. Based on the eligibility criteria (Table 1), nine children were excluded from this study; the remaining 42 (31 male and 11 female) patients were included and invited for a final follow-up examination. Parents were informed that medical records will be used for scientific purposes only, and written informed consent was obtained at the final visit. Patients were categorized into two groups based on the fixation method as follows: group A and group B. Internal fixation was performed with 2 K-wires in group A and a screw in group B. Group A comprised 22 children (16 male and six female), and group B comprised 20 children (15 male and 5 female; Fig. 1). During the initial operation, the mean age of the children was nine (median, 10.5; range, 6–14) in group A and 15 (16, 10–17) years in group B. The mean follow-up was 10 (median, 11; range, 6–15) in group A and 10 (9.5, 5–15) years in group B. Children in either group were comparable concerning demographic data (p>0.05 for gender, side, number of participants, and duration of follow-up; Table 2). The primary indication for surgical treatment was fractured with a displacement of more than 5 mm (Fig. 2). The choice of fixation type, i.e., K-wires or a screw, was determined based on the age and skeletal maturity of the patients. K-

Group A

Group B

(Kirschner wire fixation)

(Screw fixation)

(n=22)

(n=20)

Figure 1. Flow diagram of the study participants.

wires were used in younger children with years of growth remaining, whereas a screw was used in children near skeletal maturity. Relevant dislocations of the elbow (n=2 and 3 in groups A and B, respectively) were reduced at the time of admission. Concomitant fragment entrapment in the elbow joint (n=3 and 4; Fig. 3), ulnar nerve palsy (n=1 and 2), and severe valgus instability on fluoroscopy under general anesthesia during the operation (n=6 and 5 in groups A and B, respectively) were recorded.

Outcome Measures During the clinical assessment, the elbow range of motion (ROM) and valgus angle of the elbow were measured using a universal standard goniometer by the senior resident at the final follow-up. In addition, the Mayo Elbow Performance Scores (MEPS) were performed for functional assessment of the following four items: pain (max 45 points, from no pain to severe pain), stability (max 10 points, from stable to grossly unstable), ROM (max 20 points, from >100° to <50°), and daily activities (max 25 points).

Table 1. Eligibility criteria for inclusion and exclusion of the study participants Inclusion criteria

Exclusion criteria

• A diagnosis of displaced fractures of the medial humeral epicondyle

• <2 years of follow-up

• Age <18 years at the time of surgery

• Lost to follow-up

• Cases which underwent open reduction and internal fixation with either

• Open fractures

Kirschner wires or a screw with or without a washer

• Concomitant ipsilateral upper extremity fractures

• Being willing to participate in this study

• Being unwilling to participate in this study

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Table 2. Demographic characteristics of the study participants

Group A (22 children, 22 elbows)

Group B (20 children, 20 elbows)

6–14 (10.5)

10–17 (16)

<0.01a

Mean age at surgery, year

Min-Max (Median)

Mean

Female

Dominant

6–15 (11)

5–15 (9.5)

Gender Male

1.00b

Side Nondominant

0.49b

Follow-up duration, year

Min-Max (Median)

Mean

0.18a

Student’s T-test; bFisher’s exact test; *p<0.05. Min: Minimum; Max: Maximum.

During the radiographic assessment, according to the deformity classification of Skak et al.,[6] possible deformities secondary to the epicondyle fracture were examined on the final follow-up anteroposterior elbow radiographs by the senior orthopedic surgeon. Furthermore, postoperative complications were documented from medical records. Skak et al. described the five types of postoperative radiographic deformities for the medial epicondyle fractures by comparing both the elbows on equivalent AP elbow radiographs: fibrous union or pseudarthrosis, a double-contoured epicondyle, an ulnar sulcus, and hypoplasia or hyperplasia of the epicondyle.

Surgical Technique All operations were performed under general anesthesia within four days after the injury by two senior orthopedic surgeons. Children were positioned in the supine position

with the injured elbow on an arm board. Prophylactic antibiotics were administered as a single dose 30 min before skin incision and continued up to 48 hours after the operation at 6-hour intervals. After a pneumatic tourniquet was applied, the fracture site was exposed via a posteromedial incision over the medial epicondyle in all children. The ulnar nerve was routinely identified and protected but not transposed. The ulnar nerve was anteriorly transposed in only three children with ulnar nerve symptoms (n=1 and 2 in groups A and B, respectively). In group A, the fracture was fixed with two non-threaded smooth K-wires in a parallel configuration. In group B, the fragment was fixed with a 4.5-mm cannulated screw in large children and a 3.5-mm cannulated screw in smaller elbows. In three children with a fragmented epicondyle, a washer

(a)

Figure 2. The radiograph demonstrates a medial epicondyle fracture, with a considerable displacement (>5 mm).

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(b)

Figure 3. (a, b) Radiographs show an incarcerated medial epicondyle in the elbow joint (blue arrows), with valgus instability.

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Table 3. Clinical and radiographic outcomes of the children in both groups

Group A

Group B

110–140 (127.5)

115–140 (127.5)

0.43a

Range of motion degree (°), Min-Max (Median), Mean

Flexion

Extension loss*

Supination loss*

Mayo Elbow Performance Score, Min-Max (Median), Mean

127

128

5–10 (5)

5 –10 (5)

0.95b

3–10 (5)

5–10 (5)

0.53b

85–100 (95)

85–100 (94)

0.18a

1 0.34c

Hypoplasia

Hyperplasia

1 0

Radiographic deformities** (n)

Fibrous union

Ulnar sulcus deformity

Postoperative complications (n)

Pin-track infection

Superficial wound infection

0.33c

Descriptive and comparative statistics were performed for only children with extension and supination loss. Radiographic deformities were evaluated based on the classification of Skak et al. aStudent’s T-test; bMann-Whitney U test; cChi-square test p<0.05. Min: Minimum; Max: Maximum.

was added to enhance the fixation surface area and minimize the risk of more fragmentation of the epicondyle with compression. Directions of the K-wires or screws were controlled using fluoroscopy, and no olecranon fossa penetration was detected. The construct and stability were evaluated with direct observation and fluoroscopic imaging intraoperatively.

Postoperative Rehabilitation Protocol Postoperatively, the elbow was immobilized at 90° flexion and neutral rotation with an above-elbow splint (wellpadded dorsally) for three weeks. During this period, wrist and hand exercises were permitted if the pain was tolerable. From three to six weeks following the operation, all children were encouraged free elbow mobilization, using a hinge brace to preserve the elbow from valgus and varus forces. At six weeks, the brace was removed, and the children were encouraged to attend noncontact activities. At 12 weeks, returning to previous activities was permitted. The K-wires were removed under general anesthesia between the 4th and 8th weeks postoperatively.

RESULTS The clinical outcomes of patients are shown in Table 3. At the final follow-up, with favorable elbow function, all children returned to their daily life with no limitations. Regarding the MEPS, both groups exhibited similar results (p=0.18). Moreover, all children exhibited a satisfactory elbow ROM, and 140

no significant differences were observed between the two groups (p=0.43). Six and eight children in groups A and B had an extension loss with a mean degree of seven (median, 5; range, 5–10) and six (5, 5–10), respectively. Furthermore, eight and seven children in groups A and B developed supination loss with a mean degree of five (median, 5; range, 3–10) and six (5, 5–10), respectively. Additionally, physical examination revealed no cases of valgus instability. The radiographic results are presented in Table 3. Based on the method of Skak et al., one patient from each group developed a fibrous union, and one patient from each group had hypoplasia. Furthermore, one patient in group A developed epicondylar hyperplasia, and one patient in group B had nonsymptomatic ulnar sulcus deformity. No significant relationship was observed between the deformity and fixation type (p=0.34, χ2 test). In both groups of children, the radiographic solid union was obtained at an average of six (range, 4–10) and seven (range, 5–10) weeks in groups A and B, respectively (p=0.65) (Figs. 4 and 5). Concerning postoperative complications (Table 3), two patients in group A suffered from pin track infections that resolved with regular pin track dressing and antibiotics. One patient in group B developed a superficial wound infection that resolved with local wound care and oral antibiotics. No late neurological or other complications were observed at the final follow-up. No significant difference was observed in complications between groups A and B (p=0.33). Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

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(a)

(b)

(c)

Figure 4. An 8-year-old boy suffered from a fracture of the right medial humeral epicondyle because of a simple fall. (a) The initial radiograph demonstrates the displaced fragment pulled by the ulnar collateral ligament. (b) The fragment was fixed with K-wires from the medial side in an anatomic position. (c) The final follow-up radiograph shows a solid union.

(a)

(b)

Figure 5. A 14-year-old adolescent sustained a fracture of the right medial humeral epicondyle after falling on the outstretched upper extremity. (a) The initial radiograph shows the displaced fragment. (b) The fragment was fixed with a cannulated screw from the medial side in an anatomic position and the final follow-up radiograph shows solid union.

DISCUSSION Operative treatment with open reduction and internal fixation has a crucial role in avoiding the painful nonunion and minimizing the risk of symptomatic valgus instability.[5] The present study provides additional evidence that fixation with either K-wires or screws could confer proper fracture reduction and maintain stabilization for fracture healing with similar clinical and radiographic outcomes at long-term follow-up. Besides, several authors prefer K-wires in younger patients with open physis, whereas screws are mostly used for children near skeletal maturity.[1,7â&#x20AC;&#x201C;9] However, to our knowledge, the rationale behind this preference has not been investigated well. We, therefore, clarified this rationale by directly comparing the clinical and radiographic outcomes of both fixation types in children with displaced medial epicondyle fractures. Ulus Travma Acil Cerrahi Derg, January 2020, Vol. 26, No. 1

Ip and Tsang[9] reviewed 24 consecutive children with the medial humeral epicondylar fracture displaced greater than 5 mm who underwent operative treatment by one of the three methods, including two parallel K-wires, two parallel K-wires plus a tension band, and a screw plus an anti-rotation K-wire. The author suggested that two parallel K-wires plus tension band should be performed for younger children who still have growth potential because this approach minimizes the risk of developing cubitus varus deformity due to a screw across the growing apophysis. Consistently with Ip and Tsangâ&#x20AC;&#x2122;s approach, we mostly preferred a screw with or without a washer for children near skeletal maturity and K-wires for younger children with years of growth remaining. We observed no cubitus varus or valgus deformity with satisfactory ROM and MEPS. Skak et al.[6] classified the radiological deformities following displaced medial epicondyle fractures treated conservatively or surgically using K-wires, sutures, or palmar nails as follows: pseudarthrosis or a fibrous union, a double-contoured epicondyle, an ulnar sulcus, and simple hyperplasia or hypoplasia of the epicondyle. Two of these deformities were associated with the fixation type used in their study. Pseudarthrosis was noted after treatment with plaster or suturing, and hypoplasia was observed after pin fixation. Accordingly, the authors suggested that nailing causes extra damage to a likely injured growth plate, whereas inserting K-wires by drilling may cause less damage. However, they did not specify which fixation type they applied for which age group. At our institution, the choice of fixation type for displaced medial epicondyle fractures was determined based on the age and skeletal maturity of the patient. We observed four types of deformities, including a fibrous union, hypoplasia, hyperplasia, and ulnar sulcus deformity; there was no significant relationship between the deformity and fixation type. Therefore, we considered that the choice of fixation type according to skeletal maturity was likely to reduce the risk of development of such deformities. Approximately 50% of such fractures may be accompanied by elbow dislocation, and the fragment may be incarcerated within the joint with an incidence of at least 15%.[7,10] In some children, the concomitant dislocation of the elbow may spontaneously reduce and accordingly be unrecognized.[11] Compared with the literature, the present study revealed a similar rate of fragment entrapment (group A, 3/20; group B, 4/22) and a low rate of concomitant elbow dislocation (group A, n=2/20; group B, n=3/22). This low rate may be attributable to the spontaneous reduction of the elbow dislocation after the trauma. The management of coexisting ulnar nerve palsy is equivocal.[4] Most authors[12â&#x20AC;&#x201C;14] suggest that routine exploration or transposition of the ulnar nerve is not essential because the nerve may be more sensitive to partial devascularization following transposition in current trauma versus that in an 141

Ergin et al. Long-term results of surgical treatment for pediatric displaced medial epicondyle fractures

elective nontraumatic case.[14] We transposed the ulnar nerve in three children with ulnar nerve symptoms (group A, n=1; group B, n=2) and obtained complete neurological recovery. Therefore, we support the notion that anterior transposition should be only performed for children with nerve compression signs.[14] Concerning postoperative complications, three modern series reports of pediatric medial epicondyle fractures[7,9,15] were operatively treated using either K-wires or screws reported a postoperative infection rate of less than 1% (1/188, superficial wound infection). However, in contrast with these studies, we recorded two-pin track infections following Kwire fixation and one superficial wound infection following screw fixation. Other complications have not been reported in these surgical series.[7,9,15] The operative treatment of such fractures raises a concern regarding iatrogenic nerve injury. Lately, Marcu et al.[16] reported two cases of severe iatrogenic radial nerve injuries secondary to the guidewire of the cannulated fixation systems. In our case series, we did not experience such a complication. Stiffness represents the most frequent complication following elbow injuries when treated by splint immobilization. Therefore, early active elbow motion is a vital part of the postoperative rehabilitation protocol following the operative treatment.[17] Louahem et al.[15] stated that six of 139 children (4%) developed extension deficits of <20°. Similar to our postoperative rehabilitation protocol, the authors immobilized the elbow at 90° flexion and neutral rotation for a mean of four weeks and then allowed elbow mobilization. In our study, three children after K-wires fixation and two after screw fixation suffered from extension loss of <10°. Accordingly, it seems that both fixation methods can provide satisfactory elbow ROM despite a 3–4-week postoperative immobilization period to secure fixation. This study has several important limitations. The first limitation is the retrospective nature of data collection, which may raise the concern of recall bias. Another potential limitation was its relatively small sample size, including 42 fractures although our cohort size was large compared with most of the studies that we have cited. This may limit the power of the results, and therefore further studies with larger samples may identify significant differences in all the variables analyzed in the present study. Last, surgeries were performed by three different surgeons, which may have provided biased results due to the surgeon’s experience. Additionally, results in selection bias may cause differences in complication rates between the two techniques. However, as previously mentioned, the choice of fixation type was mostly determined based on skeletal maturity. Despite these limitations, this is a preliminary study to directly compare the long-term clinical and radiographic outcomes of internal fixation with either Kirschner wires or cannulated screws in children with displaced medial epicondyle fractures. 142

Conclusion We recommend operative treatment for children with medial epicondylar fractures displaced more than 5 mm. The early use of two smooth K-wires for younger children and delayed use of screw fixation for children near skeletal maturity might provide favorable clinical and radiological outcomes during long-term follow-up, with low morbidity and radiographic deformity. Informed Consent: Written informed consent was obtained from the patients for the publication of the case report and the accompanying images. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: F.B.; Design: Ö.N.E., M.D. Supervision: F.B., Ö.N.E.; Materials: M.D., F.Ş.; Data: F.Ş.; Analysis: Ö.N.E.; Literature search: M.D.; Writing: M.D.; Critical revision: F.B., Ö.N.E.. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Kamath AF, Baldwin K, Horneff J, Hosalkar HS. Operative versus nonoperative management of pediatric medial epicondyle fractures: a systematic review. J Child Orthop 2009;3:345−57. 2. Josefsson PO, Danielsson LG. Epicondylar elbow fracture in children: 35-year follow-up of 56 unreduced cases. Acta Orthopaedica Scandinavica 1986;57:313−15. 3. Duun PS, Ravn P, Hansen LB, Buron B. Osteosynthesis of medial humeral epicondyle fractures in children: 8-year follow-up of 33 cases. Acta Orthop Scandinavica 1994;65:439−41. 4. Pathy R, Dodwell ER. Medial epicondyle fractures in children. Curr Opin Pediatr 2015;27:58−66. 5. Patel NM, Ganley TJ. Medial epicondyle fractures of the humerus: how to evaluate and when to operate. J Pediatr Orthop 2012;32:S10−3. 6. Skak S, Grossmann E, Wagn P. Deformity after internal fixation of fracture separation of the medial epicondyle of the humerus. J Bone Joint Surg Br 1994;76:297−302. 7. Lee HH, Shen HC, Chang JH, Lee CH, Wu SS. Operative treatment of displaced medial epicondyle fractures in children and adolescents. J Shoulder Elbow Surg 2005;14:178−85. 8. Bulut G, Erken HY, Tan E, Ofluoglu O, Yildiz M. Treatment of medial epicondyle fractures accompanying elbow dislocations in children. Acta Orthop Traumatol Turc 2005;39:334−40. 9. Ip D, Tsang WL. Medial humeral epicondylar fracture in children and adolescents. J Orthop Surg 2007;15:170−3. 10. Wilson N, Ingram R, Rymaszewski L, Miller J. Treatment of fractures of the medial epicondyle of the humerus. Injury 1988;19:342−4. 11. Woods GW, Tullos HS. Elbow instability and medial epicondyle fractures. Am J Sports Med 1977;5:23−30. 12. Gottschalk HP, Eisner E, Hosalkar HS. Medial epicondyle fractures in the pediatric population. J Am Acad Orthop Surg 2012;20:223−32. 13. Glotzbecker MP, Shore B, Matheney T, Gold M, Hedequist D. Alternative technique for open reduction and fixation of displaced pediatric medial epicondyle fractures. J Child Orthop 2012;6:105−9. 14. Anakwe RE, Watts AC, McEachan JE. Delayed ulnar nerve palsy after

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Ergin et al. Long-term results of surgical treatment for pediatric displaced medial epicondyle fractures open reduction and internal fixation of medial epicondylar fractures. J Pediatr Orthop 2010;19:239−41. 15. Louahem DM, Bourelle S, Buscayret F, Mazeau P, Kelly P, Dimeglio A, et al. Displaced medial epicondyle fractures of the humerus: surgical treatment and results. A report of 139 cases. Arc Orthop trauma Surg 2010;130:649−55.

16. Marcu DM, Balts J, McCarthy JJ, Kozin SH, Noonan KJ. Iatrogenic Radial Nerve Injury With Cannulated FixationofMedial Epicondyle Fractures in the PediatricHumerus: A Report of 2 Cases. J Pediatr Orthop 2011;31:e13−6. 17. Ireland M, Andrews J. Shoulder and elbow injuries in the young athlete. Clin Sports Med 1988;7:473−94.

OLGU SERİSİ - ÖZET OLGU SUNUMU

Pediatrik deplase mediyal epikondil kırıklarının cerrahi tedavisinde Kirschner teli veya kanüllü vida ile internal tespitin uzun dönem sonuçlarının karşılaştırmalı çalışması: 42 olgunun 10 yıllık takip sonuçları Dr. Ömer Naci Ergin, Dr. Mehmet Demirel, Dr. Fatih Şentürk, Dr. Serkan Bayram, Dr. Fuat Bilgili İstanbul Üniversitesi İstanbul Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, İstanbul

AMAÇ: Literatürde, deplase mediyal epikondil kırıklarının cerrahi tedavisinde hangi tip tespit materyalinin kullanılacağına karar vermenin ardında yatan gerekçe yeterince araştırılmamıştır. Çalışmamızda, deplase mediyal epikondil kırığı olan çocuklarda Kirschner teli (K-teli) veya kanüllü vida ile internal tespitin uzun dönem klinik ve radyografik sonuçlarını karşılaştırıldı. GEREÇ VE YÖNTEM: 5 mm’den daha fazla yer değiştirmiş mediyal epikondil kırıkları için cerrahi tedavi uygulanmış toplam 42 çocuk iki gruba ayrıldı. Grup A, K-telleri ile internal tespit uygulanmış 22 çocuk içerirken, grup B kanüllü vida ile tespit uygulanmış 20 çocuktan oluşuyordu. Ortalama yaş grup A’da 9 yıl (ortanca, 10.5; aralık, 6–14) iken, grup B’de 15 yıldı (16, 10–17). Toplam takip süresi 10 (ortanca, 10; aralık, 5–15) yıl olarak hesaplandı. Hastaların klinik sonuçlarını değerlendirmek için, son takipteki dirsek hareket açıklığına (ROM) ek olarak Mayo Dirsek Performans Skorları (MEPS) kullanıldı. Radyografik değerlendirme sırasında, son takip radyografileri üzerinde epikondil kırığına ikincil olası deformiteler incelendi. BULGULAR: Ortalama MEPS, A ve B gruplarında sırasıyla 95 (ortanca, 95; aralık, 85–100) ve 93 (94, 85–100) olarak tespit edildi (p=0.18). ROM’da anlamlı bir fark gözlenmedi (p=0.43). Radyografik incelemede her gruptan birer hasta fibröz kaynama saptanırken, her gruptan birer hastada hipoplazi mevcuttu. Deformite ve tespit tipi arasında anlamlı ilişki saptanmadı (p=0.34, χ2 testi). TARTIŞMA: Deplase mediyal epikondil kırıklarının cerrahi tedavisinde, iskelet olgunluğuna yakın çocuklar için vida ile tespit, daha küçük çocuklar için iki adet K-teli ile internal tespit düşük morbidite ve radyografik deformite oranları ile uzun süreli takiplerde olumlu klinik ve radyolojik sonuçlar sağlayabilir. Anahtar sözcükler: Humerus mediyal epikondil kırığı; Kirschner teli ile tespit; pediatrik dirsek kırığı; vida ile tespit. Ulus Travma Acil Cerrahi Derg 2020;26(1):137-143

doi: 10.14744/tjtes.2019.77348

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Castleman's disease presenting with mechanical intestinal obstruction: A rare case Abdulcabbar Kartal, M.D.,1 Eray Atlı, M.D.,2 Gürcan Vural, M.D.,3 Murat Ferhat Ferhatoğlu, M.D.,1 Ali İlker Filiz, M.D.1 1

Department of General Surgery, Okan University Faculty of Medicine, İstanbul-Turkey

Department of Radiology, Okan University Faculty of Medicine, İstanbul-Turkey

Department of Pathology, Okan University Faculty of Medicine, İstanbul-Turkey

ABSTRACT Castleman’s disease (CD) is a lymphoproliferative disorder and the occurrence of CD in the small bowel is rare. In this study, we present one case of CD causing mechanical intestinal obstruction due to involvement of terminal ileum. A 50-year-old man was admitted to the hospital with signs and symptoms of mechanical intestinal obstruction without history previous surgery. After examination and obtaining abdominal computed tomography, diagnosis of mechanical intestinal obstruction was reached and emergency surgery was performed with a median incision. On abdominal exploration a tumor like mass that also held distal small intestine mesentery, and ileocecal valve causing complet intestinal obstruction was observed. Ileocecal resection and ileocolonic anastomosis were performed. CD is a rare entity and should be kept in mind during the differential diagnosis of mechanical intestinal obstruction provided that wall thickening in terminal ileum mimicking mass, and accompanying enlargement mesenteric lymph nodes observed during preoperative investigations or intraoperative exploration. Keywords: Castleman’s disease; lymphoproliferative disorder; mechanical intestinal obstruction; mesenteric lymph nodes; terminal ileum.

INTRODUCTION Castleman’s disease (CD) was first described as hyperplastic mediastinal lymph nodes containing interfollicular vascular proliferation in 1956 by Benjamin Castleman et al.[1] CD is a lymphoproliferative disorder and comprises two distinct diseases with different prognoses, including unicentric and multicentric. Unicentric CD (UCD) is defined as a localized disease which involves enlarged lymph node(s) in a single region of the body, whereas multicentric CD (MCD) is a systemic disease with generalized peripheral lymphadenopathy, hepatosplenomegaly, frequent fevers, and night sweats. CD may also present with a number of malignancies, including Kaposi sarcoma, Hodgkin lymphoma and non-Hodgkin lymphoma. UCD is a rare disease and its true incidence is not known

but it can be seen at any age, especially in younger adults. The median age at presentation is approximately 35 years.[2] The pathogenesis of UCD is not well understood, and viral, autoimmune, and neoplastic diseases have all been proposed as possible etiologies.[3] Although some familial cases of UCD have been reported, genomic sequencing has not been performed to identify inherited mutations.[4,5] Patients with UCD are usually asymptomatic and come to clinical attention when an enlarged lymph node is noted on physical examination or imaging studies. UCD usually affects just one lymph node or a single lymph node region. While the disease may involve all parts of the body, the mediastinum appears to be the most common part of involvement. In this study, we present one case of CD causing mechanical intestinal obstruction due to involvement of terminal ileum.

Cite this article as: Kartal A, Atlı E, Vural G, Ferhatoğlu MF, Filiz Aİ. Castleman’s disease presenting with mechanical intestinal obstruction: A rare case. Ulus Travma Acil Cerrahi Derg 2020;26:144-147. Address for correspondence: Abdulcabbar Kartal, M.D. Okan Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul, Turkey Tel: +90 216 - 494 65 26 E-mail: narcabb@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):144-147 DOI: 10.5505/tjtes.2018.42273 Submitted: 03.10.2018 Accepted: 24.12.2018 Online: 27.12.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Soyisimi et al. Castleman’s disease presenting with mechanical intestinal obstruction

CASE REPORT A 50-year-old man was admitted to the hospital with abdominal pain, nauseous, fecaloid vomiting, abdominal distention, and absent of gas and stool discharge since three days. His last bowel movement was three days ago and he reported no flatulance for three days, as well. He showed no signs of fever or chills. He had no a past history of previous hospitalizations. On physical examination, he showed signs of abdominal distension and bowel sounds were hypoactive. Tenderness was observed in all quadrant and there was rebound and guarding. Respiratory sounds were normal. The patient’s blood pressure was 140/90 mmHg, heart rate was 90 beats per minute, SpO2 was 92%, and temperature was 37.6 °C. Rutin blood tests and abdominal computed tomography (CT) were obtained. Results of blood tests revealed total protein 7.3 g/dL, albumin 4.5 g/dL, AST 10 IU/L, ALT 9 IU/L, glucose 165 mg/dL, CRP 7.6 mg/dL, WBC 16.570 /µL, neutrophils 72%, HGB 13.74%, HCT 44.17%, PLT

(a)

(b)

328.000 /µL, INR 1.43, total bilirubin 0.7 mg/dL, BUN 21 mg/ dL, creatinin 1.65 mg/dL, Na 141 mEq/L, K 4.3 mEq/L. Abdominal CT images and findings were shown in Figure 1. Because of the severe tenderness, signs of peritoneal irritation, and CT findings compatible with mechanical intestinal obstruction, emergency surgery was performed the same day with a median incision. On abdominal exploration, a tumorlike mass that also held distal small intestine mesentery, and ileocecal valve causing complet intestinal obstruction was observed. Ileocecal resection and ileocolonic anastomosis was performed. Pathological findings revealed Castleman hyaline vascular type reactive lymphoid hyperplasia with ulcerated active chronic inflammation (Fig. 2). The postoperative course was uneventful. On postoperative day 3, oral food intake was started. The patient was discharged on postoperative day 7 without any problems.

(c)

(d)

Figure 1. Abdomen CT scout image of patient in supine position (a) demonstrates distended stomach and small intestine segments with air, and diameter of the small intestine segments increased as well, compatible with intestinal obstruction. Axial contrast enhanced abdominal CT (b) demonstrates dilated small intestine segments (arrows), confirms scout image findings. Diffuse bowel wall thickening and contrast enhancement in the thickened bowel wall (arrowheads) with increased density adjacent mesentery (*) are seen in right lower quadrant, just before the terminal ileum (not shown in image). In coronal reformatted image (c), bowel wall thickening, long segmental involvement (arrowheads), and enlarged lymph nodes (arrows) in adjacent mesentery with increased density (*) are seen at right lower quadrant. In addition, involvement of terminal ileum (arrow) and lack of cecal and ascending colon involvement (arrowheads) are also seen in this coronal reformatted image (d).

(a)

(b)

(c)

Figure 2. Castleman disease of hyalin vascular type. Germinal centers are rather prominent and they Show well-developed changes (a). Scattered reticular/dendritic cells (arrow) some show dysplastic changes. Hematoxylin-Eosin stain. 100× (b). CD68 positive plasmacytoid dendritic cells in the interfollicular stroma. CD68 (514H12) Leica BOND-III mouse anti-human monoklonal antibody (c).

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DISCUSSION CD, which was reported by Castleman in 1954, is a highly heterogeneous clinicopathological entity belonging to the family of lymphoproliferative disorders.[6] Although the etiology and pathophysiology of CD’s remain unknown, potential contributors to disease development are chronic inflammation, immune deficiencies, and some autoimmune diseases. Additionally, Epstein-Barr virus, Toxoplasma, and Mycobacterium tuberculosis are among the infectious agents that are responsible for disease. Clinical and laboratory abnormalities noted in the presence of CD are associated with inflammatory mediators, particularly with interleukin-6.[7,8] CD is clinically classified into two types: unicentric and multicentric. UCD (90%) is the most commonly seen type. There are three subtype of UCD: The hyaline vascular histopathologic subtype, the plasma cell histopathologic subtype and the mixed histopathologic subtype. Multicentric type is associated with a poor prognosis. A patient diagnosed with multicentric CD should be considered as systemic, and combination treatment, should be initiated as soon as possible.[9] Patients with UCD are reported to be commonly asymptomatic and come to clinical attention when an enlarged lymph node is noted on physical examination or cause a problem. In the present study, the problem was mechanical intestinal obstruction due to enlargement of mesenteric lymph nodes and involvement of terminal ileal wall.[2] Although the radiological appearance of CD is nonspecific, UCD may also present on imaging modalities. The most common radiologic presentation is mediastinal or hilar mass on computed tomography.[10] Our patient had localized CD, and presented with clinical signs and symptoms of mechanical intestinal obstruction. After surgical treatment, the patient was followed clinically and did not have a problem. Complete resection of the involved node or organ is curative and the gold standard approach for the treatment of UCD.[11] Talat et al. in their systematic review, investigated 404 published cases of CD, and concluded that surgery is the gold standard for treatment of UCD. A systematic review of the role of surgical resection in localized CD showed that surgical resection was the most effective treatment for localized CD.[12] However, aggressive surgical treatment of CD is not recommended as this may increase the rates of morbidity and mortality among CD patients. CD is a benign disease, which may also be treated by chemoradiotherapy as an alternative to surgery or after surgery. Particularly, in the presence of unresectable unicentric CD, neoadjuvant rituximab and neoadjuvant radiotherapy can allow resection to be performed with a lower rate of morbidity given that these treatments may result in tumor shrinkage and reduced vascularity.[13] Total resection provided cure in our case presented here. 146

While mesenteric involvement in our case was unicentric, histopathological investigations indicated hyaline-vascular type CD. CD is difficult to diagnose preoperatively. The disease often presents with a solitary mass. Enlarged solitary lymph node showing homogeneous intense enhancement upon administration of contrast agent in computerized tomography should remind the diagnosis of the CD. The disease is frequently confused with malignancy as unicentric CD does not have specific radiological findings and appears as a solitary mass on radiological images.

Conclusion CD should be kept in mind during the differential diagnosis of mechanical intestinal obstruction provided that wall thickening in terminal ileum mimicking mass, and accompanying enlargement mesenteric lymph nodes observed during preoperative investigations or intraoperative exploration. In cases of UCD, complete surgical resection should be performed. Informed Consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.K., M.F.F.; Design: A.İ.F.; Supervision: A.K., M.F.F.; Materials: E.A., G.V.; Data: A.K., E.A., G.V.; Analysis: A.İ.F., A.K.; Literature search: A.K., G.V., E.A.; Writing: A.K., G.V., E.A.; Critical revision: A.İ.F., M.F.F. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Castleman B, Iverson L, Menendez VP. Localized mediastinal lymphnode hyperplasia resembling thymoma. Cancer 1956;9:822−30. 2. Keller AR, Hochholzer L, Castleman B. Hyaline-vascular and plasmacell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer 1972;29:670−83. 3. Talat N, Belgaumkar AP, Schulte KM. Surgery in Castleman’s disease: a systematic review of 404 published cases. Ann Surg 2012;255:677−84. 4. Martin C, Peña ML, Angulo F, García F, Vaca D, Serrano R. Castleman’s disease in identical twins. Virchows Arch A Pathol Anat Histol 1982;395:77−85. 5. Leslie C, Shingde M, Kwok F, Platten M, Tesfai Y, Amanuel B, et al. Tlymphoblastic proliferation and florid multifocal follicular dendritic cell proliferation occurring in hyaline-vascular Castleman disease in a patient with a possible familial predisposition. J Hematopathol 2013;6:237−244. 6. Chen J, Yang C, Liang CZ. Detection of a unicentric type of Castlemanlike mass at the site of adrenal grand: A case report and review of literature. World J Clin Cases 2018;6:683−7. 7. Ozsoy M, Ozsoy Z, Sahin S, Arıkan Y. Rare Forms of Castleman Disease Mimicking Malignancy: Mesenteric and Pancreatic Involvement. Cureus 2018;10:e2310. 8. Casper C. The aetiology and management of Castleman disease at 50 years: translating pathophysiology to patient care. Br J Haematol 2005;129:3−17. 9. Nishimoto N, Kanakura Y, Aozasa K, Johkoh T, Nakamura M, Nakano S,et al. Humanized anti-interleukin-6 receptor antibody treatment of

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Soyisimi et al. Castleman’s disease presenting with mechanical intestinal obstruction multicentric Castleman disease. Blood 2005;106:2627−32. 10. Madan R, Chen JH, Trotman-Dickenson B, Jacobson F, Hunsaker A. The spectrum of Castleman’s disease: mimics, radiologic pathol ogic correlation and role of imaging in patient management. Eur J Radiol 2012;81:123−31. 11. Jhan JH, Li CC, Wu WJ, Lee HY. Isolated retroperitoneal Castleman’s disease: A case report and literature review. Clin Case Rep

2018;6:1543−8. 12. Mitsos S, Stamatopoulos A, Patrini D, George RS, Lawrence DR, Panagiotopoulos N. The role of surgical resection in Unicentric Castleman’s disease: a systematic review. Adv Respir Med 2018;86:36−43. 13. Baek HJ, Kook H, Han DK, Shin MG, Kim HS, Hwang TJ. Unicentric Castleman disease relapsed after fituximab-CHOP chemotherapy or radiation therapy in an adolescent. J Pediatr Hematol Oncol 2012;34:206−8.

OLGU SUNUMU - ÖZET

Mekanik bağırsak tıkanmasıyla başvuran Castleman hastalığı: Nadir bir olgu Dr. Abdulcabbar Kartal,1 Dr. Eray Atlı,2 Dr. Gürcan Vural,3 Dr. Murat Ferhat Ferhatoğlu,1 Dr. Ali İlker Filiz1 Okan Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul Okan Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, İstanbul 3 Okan Üniversitesi Tıp Fakültesi, Patoloji Anabilim Dalı, İstanbul 1 2

Castleman hastalığı, lenfoproliferatif bir hastalıktır ve ince bağırsakta görülmesi nadirdir. Bu çalışmada, terminal ileum tutulumuna bağlı mekanik bağırsak tıkanıklığına neden olan bir Castleman hastalığı olgusu sunuldu. Daha önce geçirilmiş karın cerrahisi öyküsü olmayan 50 yaşında erkek hasta, mekanik bağırsak tıkanıklığı bulguları ve semptomları ile hastaneye başvurdu. Muayene ve abdominal bilgisayarlı tomografi ile mekanik intestinal obstrüksiyon tanısı konuldu ve median insizyon ile acil cerrahi girişim yapıldı. Abdominal eksplorasyonda, distal ince bağırsak mezenterini ve ileoçekal valvi tutan tümör benzeri kitlesel lezyonun intestinal obstrüksiyona neden olduğu görüldü. İleoçekal rezeksiyon ve ileokolik anastomoz yapıldı. Castleman hastalığı nadir görülen bir durumdur. Görüntülemede ya da ameliyat sırasında büyümüş lenf bezlerine eşlik eden distal ileumda kitle benzeri görünüm tespit edilmesi durumunda mekanik bağırsak tıkanıklığının ayırıcı tanısında akılda bulundurulmalıdır. Anahtar sözcükler: Castleman hastalığı; lenfoproliferatif bozukluk; mekanik intestinal obstrüksiyon; mezenterik lenf nodları; terminal ileum. Ulus Travma Acil Cerrahi Derg 2020;26(1):144-147

doi: 10.5505/tjtes.2018.42273

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A rare case of acute mechanical intestinal obstruction: Colonic endometriosis Mehmet Zeki Buldanlı, M.D.,1 İbrahim Ali Özemir, M.D.,2 Oktay Yener, M.D.,2 Yasemin Dölek, M.D.3 1

Department of General Surgery, Çankırı State Hospital, Çankırı-Turkey

Department of General Surgery, İstanbul Medeniyet University, Göztepe Training and Research Hospital, İstanbul-Turkey

Department of Medical Pathology, Çankırı State Hospital, Çankırı-Turkey

ABSTRACT Endometriosis is a disease seen in women at reproductive age, characterized by extrauterine localization of endometrial tissue. Colonic endometriosis rarely causes acute mechanical intestinal obstruction (AMIO). It may also be presented with pelvic pain, dyspareunia, tenesmus, painful defecation related to the menstrual cycle. In the literature, 3-37% of the gastrointestinal location was reported and AMIO was observed in 7-23% of these cases. There are only few cases of mechanical obstruction related to sigmoid endometriosis mimicking colon malignancy. In this study, we aim to report a case of a 40-year-old patient with AMIO developed secondary to colonic endometriosis in light of the literature. The patient was discharged with full surgical recovery after the Hartmann procedure was performed, and the pathological diagnosis was reached as endometriosis. At the post-operative sixth-month colostomy, closure and bilateral oophorectomy were performed with the patient’s will.The patient was discharged with surgical recovery and is still being regularly followed up. Endometriosis is a gynecological disease that may occur in all organ systems even though the most common location is the overs. Gastrointestinal located endometriosis should, therefore, be kept in mind in the etiology of AMIO in women at reproductive age and the related symptoms should be questioned in differential diagnosis. Keywords: Acute mechanical intestinal obstruction; endometriosis; ileus.

INTRODUCTION Endometriosis is a disease characterized by extrauterine localization of endometrial tissue. Environmental toxins, genetic predisposition, retrograd menstruation, stem cells, mullerianosis, coelomic metaplasia, neural growth, vasculogenesis and autoimmunity are thought to be responsible in the pathophysiology of endometriosis.[1,2] While the major symptom of this disease is pelvic pain, dysmenorrhea, dyspareunia, dysuria, infertility and chronic pelvic pain can be observed. 20–25% of the patients are also reported to be asymptomatic.[3] Endometriosis is mostly seen in young women in their 30s and 40s. In the literature, it was shown

that although endometriosis was mostly localized in ovarian tissue with 55–75%, it can also be seen in fallopian tubes, anterior and posterior cul-de-sac, broad and round ligaments of the uterus, peritoneal cavity, previous operation scars, umbilicus, vagina, gastrointestinal tractus, breast tissue and even in the eyes.[4] In the literature, 3–37% of the gastrointestinal location was reported and acute mechanical obstruction (AMIO) clinic was observed in 7–23% of these cases.[5] In the diagnosis of endometriosis, laboratory findings, such as CA125, estradiol, progesterone levels; imaging methods, such as ultrasonography and magnetic resonance imaging; diagnostic laparoscopy and biopsy, are commonly used.[6] Treatment methods consist of hormonotherapy,

Cite this article as: Buldanlı MZ, Özemir İA, Yener O, Dölek Y. A rare case of acute mechanical intestinal obstruction: Colonic endometriosis. Ulus Travma Acil Cerrahi Derg 2020;26:148-151. Address for correspondence: Mehmet Zeki Buldanlı, M.D. Çankırı Devlet Hastanesi, Genel Cerrahi Kliniği, Kırkevler Mah., Kastamonu Cad., Merkez, 18100 Çankırı, Turkey. Tel: +90 376 - 213 27 27 / 5003 E-mail: buldanli87@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(1):148-151 DOI: 10.5505/tjtes.2018.62705 Submitted: 19.07.2018 Accepted: 06.12.2018 Online: 04.04.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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BuldanlÄą et al. A rare case of acute mechanical intestinal obstruction: Colonic endometriosis

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Figure 1. (a) Air-fluid levels at standing direct abdominal graphy. (b) Pelvic area at contrast-enhanced abdominal computed tomography. (c) Colonic dilatation and air-fluid levels at contrast-enhanced abdominal computed tomography

analgesic medications, neural therapy and in vitro fertilization in infertile patients. Also, in selected cases, surgery is an option.[7] In this study, we aim to report a case of AMIO developed secondary to colonic endometriosis with the review of literature.

CASE REPORT In this study, a 40-year-old female patient who came to emergency service with complaints of progressive diffuse abdominal pain, distension, nausea, vomiting, inability to pass gas and constipation for four days was investigated. Physical examination revealed diffuse abdominal tenderness, distension and decreased bowel sounds. Ampulla recti were found to be empty in rectal physical examination. Leukocytosis (15.000/

Âľl) and high CRP levels (15.13 mg/dL) were detected. Intravenous contrast-enhanced abdominal computed tomography was performed after air-fluid levels were observed in standing direct abdominal graphy (Fig. 1aâ&#x20AC;&#x201C;c). Nasogastric decompression and fluid resuscitation were administered to the patient who had AMIO clinical findings. Given that the clinical findings were not regressed despite medical treatment, the patient was operated under emergency conditions. Preoperatively small intestines were

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Figure 2. The pelvic area in surgical exploration.

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Figure 3. (a) Microscopic sections from the colon specimen showing the presence of submucosal endometrial glands and stroma in the submucosal and intramuscular layers, the colonic mucosa appears normal (stained with hematoxylin-eosin, X10). (b) Microscopic sections from the specimen showing the endometriosis involving the serosa and muscularis propria of the bowel (stained with hematoxylin-eosin, X10).

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observed to be extensively dilated and edematous. 100 cc reactional free fluid was detected and aspirated from the intra-abdominal cavity. It was observed that uterus was extensively adhered to surrounding tissues and the sigmoid colon had formed a gato with the uterus (Fig. 2). The sigmoid colon mass that was separated from the uterus was resected totally with clean surgical margins with respect to oncological principles. The procedure was terminated with the Hartmann procedure after milking to reduce the distension. Preoperative gynecological consultation was taken and no additional gynecological interventions were needed. In the macroscopic examination of the resected material, a 3.5 cm cream-white mass lesion with hemorrhagic cystic spaces, extending to the serosa with a firm mucosa, which caused peritoneal surface contraction, thickened the wall and almost totally narrowed the lumen was observed. In the microscopic examination, fibrosis in serosal lipid tissue with endometrial gland and stromal tissues in the submucosa, muscularis propria and serosa with hemosiderin-laden macrophages under healthy colon mucosa was observed. The pathological diagnosis of the sigmoid colon resection material was determined to be endometriosis and reactive lymphoid hyperplasia was detected in 11 lymph nodes (Fig. 3a, b). Fluid –electrolyte replacement, analgesia and antibiotherapy were administered. The oral diet was started at post-operative day 2 after the detection of viable colostomy and fecal discharge. At post-operative day 3, dyspnea, tachycardia and saturation drop were observed. No intraabdominal pathologies were detected. Cardiac and pulmonary examinations revealed atelectasis and pneumonic consolidation. Chest disease specialist consultation was taken, and the patient’s complaints were relieved after medical treatment. The patient had no additional complaints and was discharged from the hospital on post-operative day 7 with full recovery. Dienogest (Visanne®) 2 mg pills were administered to the patient according to gynecological consultation. After medical controls, at post-operative sixth month, colostomy closure and bilateral oophorectomy were performed with the patient’s will. The patient was discharged with surgical recovery and is still regularly being followed up in general surgery and gynecology clinics. Written informed consent was obtained from the patient for the publication of this case report.

DISCUSSION Acute mechanical intestinal obstruction is one of the most common causes of acute abdomen and mostly arises from adhesions, malignancies, or intestinal herniation. It is usually presented with nausea, vomiting, colic abdominal pain and abdominal distension.[8] Although rare, there are a few reported cases of AMIO that arise from colonic endometriosis reported in the literature, especially in young female patients, it should be kept in mind as an etiological factor.[9] 150

As colonic endometriosis does not have pathognomonic symptoms, such as other gastrointestinal pathologies, it can interfere with diagnoses, such as irritable bowel syndrome, inflammatory bowel diseases, ischemic colitis or even malignancy.[10] In our case, the etiological cause was determined with histopathological examination. It was reported in the literature that laparoscopic segmentary resection and anastomosis following decompression with endoscopic stenting could be performed to avoid stoma in cases presented with AMIO caused by colonic endometriosis.[11,12] In our case, colonoscopy was not performed because the patient had progressing acute abdomen findings. Although gastrointestinal localization is rare in literature, it has been reported that it is most commonly found in the rectosigmoid colon, and it is reported that women with intestinal endometriosis can be presented with severe abdominal pain due to intestinal motility.[13] In our case, we also found that endometriosis was sigmoidal. The clinical presentation of colonic endometriosis simulates colonic carcinomas with imaging findings, such as intestinal wall thickening and intraoperative macroscopic findings, such as adhesive mass lesions. Therefore, radical resection is required during operation.[14] Our case was performed for the resolution of the emergency pathology, but the proximal, distal and radial surgical margins were established at appropriate width, and a perioperative gynecology consultation was performed. In vitro fertilization (IVF) therapy is tried in appropriate female patients with infertility, but symptomatic exacerbations can be detected in this patient group according to organ or tissue in which endometriosis is placed. Seyer-Hansen and colleagues retrospectively screened the cohort of 76 patients. Nine patients had bowel-related symptoms and two patients had colonic AMIO. IVF therapy was terminated in all 11 patients.[15] As a result, endometriosis is a gynecological entity capable of holding all organs, and gastrointestinal placement should be kept in mind in the etiology of AMIO, especially in female patients in the reproductive period. However, in addition to case reports identified in the relevant literature on this subject, there is a need for serials and reviews with a large number of patients. Informed Consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: M.Z.B., İ.A.Ö.; Design: M.Z.B., İ.A.Ö.; Supervision: M.Z.B., İ.A.Ö.; Fundings: M.Z.B., İ.A.Ö., O.Y., Y.D.; Materials: M.Z.B., Y.D.; Data: Ulus Travma Acil Cerrahi Derg, November 2020, Vol. 26, No. 1

Buldanlı et al. A rare case of acute mechanical intestinal obstruction: Colonic endometriosis

M.Z.B., O.Y., Y.D.; Analysis: M.Z.B., İ.A.Ö., O.Y., Y.D.; Literature search: M.Z.B., O.Y.; Writing: M.Z.B.; Critical revision: İ.A.Ö., O.Y. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

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Adhesions: Etiology, Pathophysiology, and Clinical Significance. Dig Surgery 2001;18:260−73. 8. Jackson PG, Raiji MT. Evaluation and management of intestinal obstruction. Am Fam Physician 2011;83:159−65. 9. Lukovich P, Csibi N, Rigó J Jr, Bokor A. Bowel endometriosis: new challenge for gastroenterology and surgery? Three cases of endometriosis caused large bowel ileus and review of the literature. Orv Hetil 2016;157:1960−6. 10. Bidarmaghz B, Shekhar A, Hendahewa R. Sigmoid endometriosis in a post-menopausal woman leading to acute large bowel obstruction: A case report. Int J Surg Case Rep 2016;28:65−7. 11. Calcagno P, Viti M, Cornelli A, Galli D, D’Urbano C. Intestinal obstruction caused by endometriosis: Endoscopic stenting and expedited laparoscopic resection avoiding stoma. A case report and review of the literature. Int J Surg Case Rep 2018;44:75−7. 12. Allan Z. A case of endometriosis causing acute large bowel obstruction. Int J Surg Case Rep 2018;42:247−9. 13. Acar T, Acar N, Çelik SC, Ekinci N, Tarcan E, Çapkınoğlu E. Endometriosis within the sigmoid colon/extragenital endometriosis. Ulus Cerrahi Derg 2015;31:250−2. 14. Varras M, Kostopanagiotou E, Katis K, Farantos Ch, Angelidou-Manika Z, Antoniou S. Endometriosis causing extensive intestinal obstruction simulating carcinoma of the sigmoid colon: a case report and review of the literature. Eur J Gynaecol Oncol 2002;23:353−7. 15. Seyer-Hansen M, Egekvist A, Forman A, Riiskjaer M. Risk of bowel obstruction during in vitro fertilization treatment of patients with deep infiltrating endometriosis. Acta Obstet Gynecol Scand 2018;97:47−52.

OLGU SUNUMU - ÖZET

Nadir görülen bir akut mekanik intestinal obstrüksiyon olgusu: Kolonik endometriozis Dr. Mehmet Zeki Buldanlı,1 Dr. İbrahim Ali Özemir,2 Dr. Oktay Yener,2 Dr. Yasemin Dölek3 Çankırı Devlet Hastanesi, Genel Cerrahi Kliniği, Çankırı İstanbul Medeniyet Üniversitesi, Göztepe Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul 3 Çankırı Devlet Hastanesi, Tıbbi Patoloji Kliniği, Çankırı 1 2

Endometriozis, üreme çağı kadınlarda görülen, endometrium dokusunun uterus dışında yer alması ile kendini gösteren bir hastalıktır. Kolonik endometriozis menstrüal siklusla ilişkili pelvik ağrı, disparoni, tenesmus ve ağrılı dışkılama şikayetleri ile ortaya çıkabildiği gibi, nadiren akut mekanik intestinal obstrüksiyona (AMİO) da yol açabilmektedir. Literatürde %3–37 oranında gastrointestinal yerleşim bildirilmiş olup bu olguların da %7– 23’ünde AMIO kliniği bildirilmiştir. Literatürde kolon malignitesini taklit eden sigmoid endometriozise bağlı az sayıda mekanik obstrüksiyon olgusu bulunmaktadır. Biz de kolonik endometriozise ikincil olarak gelişen AMİO saptanan 40 yaşındaki kadın hastayı literatür eşliğinde sunmayı amaçladık. Hartmann prosedürü uygulanan ve cerrahi tam iyileşme ile taburcu edilen hastada patolojik incelemede endometriozis tespit edildi. Ameliyat sonrası 6. ayda kolostomi kapatılması ve kendi isteğiyle bilateral ooferektomi operasyonu uygulanan hastanın takipleri devam etmektedir. Endometriozis tüm organları tutabilen jinekolojik bir hastalık olup gastrointestinal yerleşimi AMİO etiyolojisinde özellikle reprodüktif dönemdeki kadın hastalarda akılda tutulmalı ve ilişkili semptomlar sorgulanmalıdır. Anahtar sözcükler: Akut mekanik intestinal obstrüksiyon; endometriozis; ileus. Ulus Travma Acil Cerrahi Derg 2020;26(1):148-151

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