TJTES 2020-3

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ISSN 1306 - 696X

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

Volume 26 | Number 3 | May 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, Ali Hakan Durukan Ortopedics and Traumatology Mahmut Nedim Doral, Ali Erşen Plastic and Reconstructive Surgery Figen Özgür, Atakan Aydın Pediatric Surgery Aydın Yağmurlu, Ebru Yeşildağ Thoracic Surgery Alper Toker, Akif Turna Urology Ali Atan, Öner Şanlı Vascular Surgery Cüneyt Köksoy, Mehmet Kurtoğlu Emergency Medicine Burak Katipoğlu, Bülent Erbil Gynecology and Obstetrics Recep Has, Kazım Emre Karaşahin

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): May (Mayıs) 2020 • This publication is printed on paper that meets the international standard ISO 9706: 1994 (Bu dergide kullanılan kağıt ISO 9706: 1994 standardına uygundur.)

KARE P U B L I S H I N G

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 3 May - Mayıs 2020

Contents - İçindekiler Review - Derleme 335-342 Recommendations for trauma and emergency general surgery practice during COVID-19 pandemic COVID-19 pandemisi sırasında travma ve acil cerrahi uygulamaları için öneriler

Gök AFK, Eryılmaz M, Özmen MM, Alimoğlu O, Ertekin C, Kurtoğlu MH

Experimental Studies - Deneysel Çalışma 343-350 Effects of dabigatran and fondaparinux on degloving injuries: An experimental study Avülsiyon yaralanmalarında fondaparinuks ve dabigatranın etkileri: Deneysel bir çalışma

Ural A, Bilgen F, Altıntaş Aykan D, Bahar AY, Bekerecioğlu M, Altıntaş Ural D 351-360 The protective effects of lycopene on ischemia/reperfusion injury in rat hind limb muscle model Sıçan arka uzuv kas modelinde iskemi/reperfüzyon hasarına yönelik likopenin koruyucu etkisi

Kirişçi M, Güneri B, Seyithanoğlu M, Kazancı Ü, Doğaner A, Güneş H 361-365 Immediate versus delayed primary repair of the sciatic nerve in a nerve transaction model in rats Sıçanlarda sinir transeksiyon modelinde siyatik sinirin acil ve gecikmeli primer onarımı

Tufan A, Karagöz Güzey F, Eren B, Taş A, İşler C, Kahraman Akkalp A, Güleç İ, Yayla VA, Çabalar M 366-372 The protective effects of adalimumab on intestinal injury induced with infrarenal aortic occlusion İnfrarenal aort oklüzyonu ile oluşan intestinal hasarında adalimumab’ın koruyucu etkisi

Pergel A, Tumkaya L, Demiral G, Çolakoğlu MK, Kalcan S, Özdemir A, Mercantepe T, Erdivanlı B, Yılmaz A 373-383 The healing effects of Hyperium perforatum (St. John’s Wort) on experimental alkaline corrosive eosephageal and stomach burns Deneysel alkali koroziv ösefageal ve mide yanıklarında Hyperium perforatum’un (Sarı Kantaron) iyileştirici etkisi

Güvenç E, Kıyan S, Uyanıkgil Y, Çetin EÖ, Karabey F, Çavuşoğlu T, Burak Gökçe

Original Articles - Orijinal Çalışma 384-388 Hem-o-lok clips versus intracorporeal knotting for the closure of the appendix stump in laparoscopic appendectomy: A prospective randomized study Laparaskopik apendektomide apendiks güdüğünün kapatılmasında intrakorporial sütüre karşı hem-o-lok clips: Randomize ileriye yönelik çalışma

Üreyen O, Tan S, Dadalı E, Yıldırım M, İlhan E 389-395 Comparison of thiol/disulphide homeostasis with modified Alvarado and RIPASA scores in the diagnosis of acute appendicitis Akut apandisit tanısında tiyol/disülfit homeostazının modifiye Alvarado ve RIPASA skorları ile karşılaştırılması

Gökhan S, Aydın İE, Pamukçu Günaydın G, Yıldırım Ç, Tanrıverdi F, Gürü S, Kahraman FA, Erel Ö 396-404 Perioperative outcomes of the patients treated using laparoscopic cholecystectomy after emergent endoscopic retrograde cholangiopancreatography for bile duct stones: Does timing matter? Safra kanalı taşları için yapılan acil endoskopik retrograd kolanjiyopankreatografi sonrası laparoskopik kolesistektomi uygulanan hastaların perioperatif sonuçları: Zamanlama önemli mi?

Şenocak R, Çelik SU, Kaymak Ş, Hançerlioğulları O 405-410 Evaluation and comparison of tick detachment techniques and technical mistakes made during tick removal Kene çıkartım tekniklerinin değerlendirilmesi ve karşılaştırılması ile kene çıkarma sırasında yapılan teknik hatalar

Şahin AR, Hakkoymaz H, Taşdoğan AM, Kireçci E 411-417 Emergency surgery in geriatrics: A retrospective evaluation in a single center Geriatrik hastada acil cerrahi: Tek merkezde geriye dönük değerlendirme

Sezen Ö, Çevik B Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

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

Number - Sayı 3 May - Mayıs 2020

Contents - İçindekiler 418-424 Decompressive craniectomy in traumatic brain injury: Transcranial Doppler sonography used as a guide Travmatik beyin hasarında dekompresif kraniektomi: Transkranial Doppler ultrasonografi yol gösterici olabilir mi?

Sarı R, Bölükbaşı FH, Kahraman Özlü EB, Işık N, Güra Çelik M, Elmacı İ

425-430 The role of trauma mechanism, fracture pattern and fixation technique on clinical outcomes and epiphyseal growth arrest in the surgical treatment of distal tibial epiphysiolysis Distal tibial epifizyolizin cerrahi tedavisinde travma mekanizması, kırık paterni ve fiksasyon tekniğinin klinik sonuçlar ve epifiz büyümesinin durması üzerine etkisi

Aslantaş FÇ, Yalın M, İlter MH, Bayrak A, Edipoğlu E, Tanrıverdi B, Duramaz A, Bilgili MG 431-438 Computed tomography vs. magnetic resonance imaging in unstable cervical spine injuries Anstabil servikal yaralanmalarda bilgisayarlı tomografi ve manyetik rezonans görüntüleme bulgularının karşılaştırılması

Songür Kodik M, Eraslan C, Kitiş Ö, Altuncı YA, Biçeroğlu H, Akay A

439-444 Effect on mortality of treatment method and surgery time for hip fracture patients aged over 65 years Altmış beş yaş üstü kalça kırığı olgularında tedavi yöntemi ve ameliyata alınma zamanının mortaliteye etkisi

Ekici C, Pazarcı Ö, Kılınç S, Öztemür Z, Öztürk H, Tezeren G, Bulut O

445-452 Effects of different anesthesia techniques on intraoperative blood loss in acetabular fractures undergoing the Modified Stoppa approach Modifiye Stoppa yaklaşımı ile opere edilen asetabulum kırıklarında farklı anestezi tekniklerinin intraoperatif kan kaybı üzerine etkisi

Açan AE, Kılınç CY, Gültaç E, Altıparmak B, Uysal Aİ, Hürriyet Aydoğan N

453-461 Associations between initial injury severity in acute hand, wrist or forearm injuries and disability ratings and time to return to work Akut el, el bileği ya da önkolyaralanmalarındayaralanmanın ciddiyeti ile özürlülük oranları ve işe geri dönüş zamanı arasındaki ilişki

Çapkın S, Cavit A, Yılmaz K, Erdoğan E, Kaleli T

462-468 Compliance with PECARN head injury decision rules in children under two years old İki yaşından küçük çocuklarda PECARN kafa kravması klinik karar kurallarına uyum

Gerilmez A, Çalışaneller AT

Case Series - Olgu Serisi 469-474 The role of VATS in the diagnosis and treatment of diaphragmatic injuries after penetrating thoracic traumas Penetran toraks travmalarından sonra görülebilen diyafragma yaralanmalarının tanı ve tedavisinde VATS’nin rolü

Yanık F, Karamustafaoğlu YA, Yörük Y

Case Reports - Olgu Sunumu 475-481 Transcatheter embolization in pediatric blunt renal trauma: Case report and review of the literature Pediatrik künt renal travmalarda transkateter embolizasyon: Olgu sunumu ve literatür derlemesi

Kartal İ, Durmaz HA, Çimen SG, Çimen S, Ersoy H

482-485 Surgical approach for acute ischemic colitis after scuba diving: A case report Tüplü dalış sonrası gelişen akut iskemik kolit için cerrahi yaklaşım: Olgu sunumu

Choi ES, Kwak HD, Ju JK

486-488 Rhinoceros-related delayed traumatic diaphragmatic rupture Gergedanın neden olduğu gecikmiş travmatik diyafragma rüptürü

Sebastian M, Abdullah A, Abusharia M, Abu-Zidan FM 489-492 Torsion of wandering spleen nine years after gastric volvulus: Effect of multiparity? Gastrik volvulustan dokuz yıl sonra görülen gezici dalak torsiyonu: Multiparitenin etkisi?

Karaisli S, Acar T, Acar N, Kamer E, Hacıyanlı M

493-495 A rare case: Isolated superior mesenteric vein injury occurring after blunt abdominal trauma Nadir bir olgu: Künt abdominal yaralanma sonucu gelişen izole süperior mezenterik ven yaralanması

Kubat M

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Recommendations for trauma and emergency general surgery practice during COVID-19 pandemic Ali Fuat Kaan Gök, M.D.,1 Mehmet Eryılmaz, M.D.,2 Mehmet Mahir Özmen, M.D.,3 Orhan Alimoğlu, M.D.,4 Cemalettin Ertekin, M.D.,1 Mehmet Hamdi Kurtoğlu, M.D.1 1

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

2

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

3

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

4

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

ABSTRACT COVID-19 is a new disease, based on currently available limited information, older adults and people of any age who have severe underlying medical conditions may be at higher risk for severe illness from COVID-19. People of all age groups are also at risk. Healthcare providers have always been the professionals most exposed to the risk of contracting to any kind of infection due to the nature of their profession. Elective interventions have been postponed to give care of patients with COVID-19. However, some interventions cannot be delayed, such as trauma surgery, acute abdomen, and emergency endoscopies. To maintain the sustainability of the healthcare system, the protection of healthcare providers should be the top priority. On the other hand, patients, who need emergency healthcare, should also be provided with appropriate treatment. Healthcare professionals should choose a treatment method appropriately in the circumstances to protect themselves and their patients as much as possible. This paper aims to summarize how a surgeon may act appropriately when an intervention is inevitable during the COVID-19 pandemic. Keywords: Coronavirus; COVID-19; emergency surgery; endoscopy; trauma.

INTRODUCTION

BACKGROUND

Many people say that we, all the world, are at war against an insidious and invisible enemy. Health-care providers have always been the professionals most exposed to the risk of contracting to any kind of infection due to the nature of their profession. For the sustainability of health-care during the Coronavirus Disease 2019 (COVID-19) Pandemic, these valuable and necessary people, who fight in the front line, should be protected from the infection as possible as it can. Elective interventions have been postponed to provide care for patients with COVID-19. However, some interventions cannot be delayed, such as trauma surgery, acute abdomen, and emergency endoscopies. This paper aims to summarize how a surgeon may act appropriately when an intervention is inevitable even if he or she has a patient with confirmed, suspected, or not COVID-19.

COVID-19 is an infectious disease that arises from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At the beginning of December 2019, several cases of pneumonia of unknown etiology have been reported in Wuhan, Hubei province.[1,2] On 7 January 2020, a novel coronavirus was identified by the Chinese Center for Disease Control and Prevention from the throat swab sample of a patient and was subsequently named 2019-nCoV by World Health Organization. Since then, the virus has spread worldwide, which leads to the ongoing coronavirus pandemic in 2019–20. The World Health Organization (WHO) declared the 2019–20 coronavirus outbreak a pandemic on 11 March 2020.[3,4] COVID-19 is a new disease, based on currently available limited information, older adults and people of any age who have

Cite this article as: Gök AFK, Eryılmaz M, Özmen MM, Alimoğlu O, Ertekin C, Kurtoğlu MH. Recommendations for trauma and emergency general surgery practice during COVID-19 pandemic. Ulus Travma Acil Cerrahi Derg 2020;26:335-342. Address for correspondence: Ali Fuat Kaan Gök, M.D. İstanbul Üniversitesi İstanbul Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, 34093 İstanbul, Turkey Tel: +90 212 - 414 20 00 E-mail: afkgok@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):335-342 DOI: 10.14744/tjtes.2020.79954 Submitted: 17.04.2020 Accepted: 17.04.2020 Online: 17.04.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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severe underlying medical conditions may be at higher risk for severe illness from COVID-19.[5,6] People of all age groups are also at risk. A recent review and meta-analysis showed that the most common symptoms in patients with SARS-CoV-19 infection were fever, cough, muscle aches, and/or fatigue, and dyspnea.[7] In COVID-19, real-time reverse transcriptionpolymerase chain reaction (RT-PCR) of viral nucleic acid is regarded as the reference standard to confirm the diagnosis. [8] Lymphocytopenia and elevated alanine aminotransferase, D-Dimer, serum ferritin, creatine kinase, and disease severity were reported to be associated with intensive care unit admission. Older age, elevated d-dimer levels, and high SOFA score could indicate that patients with COVID-19 who have a poor prognosis.[6] Direct chest X-Rays may be normal in early or mild disease. The most common chest X-Ray abnormalities reported were bilateral opacities, multiple groundglass shadows, infiltrate shadows and consolidation in the lungs, and thickening of the pulmonary texture. Some chest computed tomographic (CT) findings may be characteristic of COVID-19. The most frequent CT abnormalities were ground-glass opacities, septal thickening, and parenchymal consolidation. CT abnormalities are more likely to be bilateral, have a peripheral distribution, and involve the lower lobes.[7,9,10] The same review mentioned before showed that mortality among the patients infected with SARS-CoV-19 was 3.0%, and most of the data were from China. In epidemiological studies from China, male sex, age ≥60 years, delay in diagnosis, and diagnosis of severe pneumonia were associated with increased mortality rates.[7]

RECOMMENDATIONS Since the announcement of the first cases of COVID-19 centers, as in all the health-care systems, have been trying to be adapting the new situation, and various preliminary guidelines have been published.[11–16] In this section, evidence-based recommendations are presented based on current data. The summary of recommendations can be seen in Table 1.

A. Organization 1. A triage center should be established. Hospitals should reorganize to identify and isolate patients with COVID-19 symptoms at the first point of contact with the health care system. Patients should be triaged according to the testing algorithm of the facility, and initial testing should optimally be performed in a manner separated from the general patient population. All patients, including minor trauma patients, must undergo triage first and then transferred to if they have no suspicion of COVID-19. If there is suspicion, they should be admitted to a dedicated area. Health care should be given to these patients by specially prepared staff and observed or operated in a dedicated area. Thus, staff and patients without COVID-19 can be protected from contracting the virus. Hemodynamically unsta336

Table 1. Summary of the recommendations A. Organization (refer to section A) • Establish a triage center • Triage all patients except hemodynamically unstable • Set up a designated area for providing care to a patient with suspected or confirmed COVID-19 • Restructure the team for minimizing the number of staff • Restrict clinic visits of the students and non-essential personnel B. Admission (refer to section B) • Have all patients wear masks • Use PPE • Ask COVID-19 symptoms, travel and exposure history • Measure body temperature • Take the nasopharyngeal swab for suspected cases • Consider additional tests according to current guidelines and availability • Do not delay patient evaluation, especially for trauma patients • Add a chest CT into routine tests • Consider nonoperative management if appropriate C. Operating room (refer to section C) • Establish a dedicated OR for patients with suspected or confirmed COVID-19 • Take appropriate precautions and use PPE for droplet contact • Treat all patients as presumed COVID-19 positive if they have symptoms/exposure history • Restrict non-essential staff and keep additional personnel out of OR • Do not take personal items to OR • Keep only necessary materials for the surgery within OR • Wear and discard all disposable protective equipment after each case • Use an aspirator to reduce the smoke exposure • Use filter devices for laparoscopic procedures • Choose an appropriate approach to minimize OR time and maximize staff safety D. Endoscopy (refer to section D) • Do urgent endoscopic procedures only (stop bleeding, stenting for obstruction) • Take appropriate precautions and use PPE for droplet contact • Consider an alternative method to replace endoscopic procedure if possible OR: Operating room; PPE: Personal protective equipment

ble trauma patients or major multiple trauma patients should immediately admit to ACS without undergoing triage. Establishing a triage center, such as in a tented environment or designated area within a facility, could help to make possible that policy.[13,17] Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


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2. The number of personnel should be minimized at the shift and bedside to protect health-care providers from the cumulative viral burden. Serious challenges in responding to COVID-19 are protecting health-care providers and preventing nosocomial infection, which have been significant problems in China and Italy that worst-affected country of Europe.[18] Restructuring teams and minimizing the number of providers are crucial policies to reduce the number of trauma/emergency surgery providers in the hospital simultaneously. Thus, exposure risk could be decreased and preserve staff.[13] Rounds should be done with as few staff as possible. Routine training sessions for residents and clinical meetings such as core lectures, mortality and morbidity meetings can be held by teleconferences. Clinic visits of non-essential personnel and students should be restricted for their own protection and personal protective equipment (PPE) saving.[19]

B. Admission 1. A face mask must be placed on the patient, even if the patient has no upper respiratory symptoms. According to a Chinese study, among of 262 patients, 46 (17.6%) were severe cases, 216 (82.4%) were common cases, which including 192 (73.3%) mild cases, 11 (4.2%) non-pneumonia cases and 13 (5.0%) asymptomatic cases, respectively. [20] Also, Mizumoto et al.[21] showed that the estimated asymptomatic proportion was 17.9% (95% credible interval (CrI): 15.5–20.2%) within the population onboard a cruise ship called the Diamond Princess. However, in an open letter to the authorities in the Tuscany region, Romagnani wrote that the vast majority of people infected with COVID-19, 50–75% were asymptomatic, but represented “a formidable source” of contagion.[22] The data show that between 5% and 80% of people testing positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may be asymptomatic. According to data, all patients must wear a face mask; relatives of patients entered the emergency department should be limited. If a companion needed, he or she must wear a mask as well. It is essential to reduce unwitting transmission of the virus from asymptomatic carriers. 2. Health-care providers should take appropriate precautions and use personal protective equipment for droplet contact. Due to the high contagiousness and rapid spread of SARSCoV-2, a significant proportion of cases are related to occupational exposure. As cases increased and considering the increasing number of admissions to the emergency departments, health-care providers should be considered as a highrisk group to acquire this infection. In a case series of 138 patients treated in a Wuhan hospital, 40 patients (29% of cases) were hospital staff. Among the affected personnel, 31 (77.5%) worked on general wards, seven (17.5%) in the emergency department, and two (5%) in the intensive care unit.[23] In Turkey, there are 601 health-care providers infected with SARS-CoV-2 so far.[24] Especially in trauma settings, due to Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

the urgency of the incident, health-care providers must not act recklessly. All teams must prepare, take appropriate precautions, and use PPE for droplet contact to protect themselves. 3. Patients should be questioned for COVID-19 symptoms, fever, cough or sneeze, exposure, and travel history, but the patient evaluation must not be delayed to asses COVID-19 status, especially for trauma patients. Frequently reported symptoms of patients with COVID-19 are fever, cough, myalgia or fatigue, shortness of breath, and gastrointestinal symptoms, such as diarrhea and nausea.[23,25,26] Patients must be carefully questioned for these symptoms, exposure, and travel history due to the high contagiousness of SARS-CoV-2. The body temperature of all patients should be measured and recorded. Especially in unconscious trauma patients, the presence of fever should be considered concerning COVID-19, if it cannot be explained due to trauma. It should be kept in mind that delays in diagnosis and treatment increase complications in trauma patients.[27,28] 4. Appropriate laboratory tests for COVID 19 should be chosen The presence of SARS-CoV-2 virus and antibodies produced in response to infection can be detected with several methods. In COVID-19 diagnosis, RT-PCR of viral nucleic acid is regarded as the reference standard. The RT-PCR test performed with nasopharyngeal and throat swabs is only reliable in the first week of the disease. Some studies reported that potentially high false-negative rate of real-time reverse-transcriptase RT-PCR testing for SARS-CoV-2 and patients experienced a “turn positive” of nucleic acid detection by RT-PCR test for SARS-CoV-2 after two consecutive negative results. [19,30] For suspected cases, the nasopharyngeal swab should be taken, but waiting for the test results should not delay treatment. Serology tests for detecting the antibody can also be useful for COVID-19 diagnosis if available. IgM antibodies to SARS-CoV-2 are generally detectable in the blood several days after the initial infection.[31] There is no evidence to indicate that trauma patients are at higher risk than the general population and, as such, should be screen according to institutional and national policy for asymptomatic patients.[32] In COVID-19, lymphocytopenia, elevated alanine aminotransferase, lactate dehydrogenase, D-Dimer, serum ferritin, creatine kinase are associated with poor prognosis as mentioned before. Some of these tests, such as D-Dimer and creatine kinase, could be abnormal in emergent conditions, especially for trauma patients with extensive soft tissue injuries. However, they may be good negative predictors.[33,34] 5. A chest CT scan should be added into routine diagnostic tools to detect COVID-19 pneumonia, even if the patient has no symptoms. Recent studies addressed the importance of chest CT exam337


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(a)

(b)

(c)

Figure 1. (a) Admission chest CT of a mesenteric ischemia case. There was no significant abnormality. (b) Chest CT of the same patient, seven days after index operation. The second chest CT showed that there were ground-glass opacities, septal thickening, and parenchymal consolidation bilaterally. (c) Chest CT of a patient with cholangitis and asymptomatic COVID-19 who was planned to undergo ERCP. CT showed that there was ground-glass opacity at the right lung. The patient underwent percutaneous transhepatic biliary drainage.

ination in COVID-19 patients with false negative-PCR results and reported the CT sensitivity as 98%.[35] The hallmarks of COVID-19 infection on imaging are bilateral and peripheral ground-glass and consolidative pulmonary opacities, sometimes with a rounded morphology and peripheral lung distribution.[36] However, intensification of a crazy-paving pattern, an increase in the number of involved lobes, and the appearance of consolidative opacities occurred in most patients over time. On average, CT findings were most prominent on day 10 of the disease. After day 14, improvement in imaging findings was reported in 75% of the patients, including decreased number of involved lobes and resolution of crazy paving pattern and consolidative opacities.[37] A recent study showed that 54% of the asymptomatic patients had pneumonic changes on chest CT,[38] but it should be kept in mind that 56% of the patients in the early period of the disease may have a normal CT.[39] If the patient develops symptoms and

(a)

the symptoms cannot be explained due to the clinical status of the patient, a new evaluation should be required (Figs. 1ab, 2). It should also be noted that it may take 4–120 hours to obtain PCR results; this is not suitable for acute care patients. Due to its wide availability and fast examination time, the supplemental role of chest CT to RT-PCR is growing for early detection of patients with COVID-19 pneumonia. 6. Non-operative management should be considered whenever it is clinically appropriate for the patient. Uncomplicated acute appendicitis may be treated with intravenous antibiotics, then transition to peroral antibiotics. In selected cases, the nonsurgical treatment group shows a relapse rate of approximately 14% in one year.[40] Also, high failure rates of conservative approach (30–50%) have been noted with appendicolith and with CT evidence of disease extension outside of the right lower quadrant.[41,42] Conservative

(b)

Figure 2. (a) A surgeon who wore enhanced droplet/airborne PPE. (b) The ACS team who worn enhanced droplet/airborne PPE in operation for a patient with suspected COVID-19.

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treatment of complicated appendicitis may require radiologicguided drainage of a peri-appendiceal abscess with intravenous antibiotics. However, no consensus exists among surgeons regarding the optimal treatment for patients with complicated appendicitis.[43] Surgical treatment should be considered for patients with complicated appendicitis or COVID-19 negative patients with uncomplicated appendicitis. Acute calculous cholecystitis can be treated with appropriate antimicrobial agents. Percutaneous cholecystostomy is a potential alternative to cholecystectomy. Percutaneous cholecystostomy should be used if antibiotic treatment fails.[44] Cholecystectomy can be postponed for patients with mild to moderate gallstone pancreatitis, but the possibility of recurrence should be considered.[45] Symptomatic patient with infected pancreatic necrosis usually requires intervention, although a small number of patients have been shown to recover with antibiotics only.[46] If the patient deteriorates, a step-up approach starting with percutaneous or endoscopic drainage is indicated, but the risks of the endoscopic approach mentioned below should be noted.[47] To avoid the risks of endoscopy, a single-stage open necrosectomy should be considered. Patients with Hinchey 4 complicated diverticulitis should undergo surgery. Patients with Hinchey 3 and 2 can be treated with intravenous antibiotics and radiologic-guided abscess drainage. CT-proven uncomplicated (Hinchey 1a and 1b) diverticulitis patients can be treated outpatient with peroral antibiotics. Also, patients with isolated pericolic extraluminal air can be treated conservatively as well.[44] Non-operative management of hemodynamically stable trauma patients with solid organ injury is appropriate for selected patients. However, abnormal clotting, apparently resulting from endothelial damage, has been described in patients with severe COVID-19 disease, and initiating prompt anticoagulation therapy, is recommended in all severe COVID-19 patients.[6,48] Initiating anticoagulation therapy may lead to non-operative management to fail. In these patients, mechanical venous thromboembolism prophylaxis should be applied and observed closely. High D-dimer levels seen in these patients point to abnormal coagulation throughout the body. The development of thrombosis is thought to be due to endothelial damage that arises from the virus, so the mechanical prophylaxis may not be able to prevent thrombosis. Interventional radiologic techniques, such as embolization of a pseudoaneurysm, percutaneous drainage of a biloma, intraabdominal blood, or abscess hemorrhage could apply safely with proper precautions taken. If needed, an aerosol-generating procedure such as bag masking, intubation, bronchoscopy, and chest tube application, should only be performed wearing enhanced PPE. For a patient with COVID-19 for whom surgery is mandaUlus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

tory, such as hemodynamically unstable trauma patients or ruptured abdominal aortic aneurysm, hollow viscus perforation, intestinal ischemia, and intestinal obstruction, an appropriate surgical approach, should wisely be chosen and applied as mentioned below. 7. Operating Room A dedicated operating room (OR) should be available for confirmed or suspected COVID-19 patients. All patients must be treated as presumed COVID-19 positive if they have symptoms/exposure history that warrants testing or are unable to provide information such as unconscious trauma patients. A recent study showed that SARS-CoV-2 could remain viable in aerosols throughout the duration of the experiment (3 hours), and SARS-CoV-2 is more stable on plastic and stainless steel than on copper and cardboard. The viable virus can be detected up to 72 hours after application to these surfaces.[49] Thus, the number of OR staff should be minimized, and all additional personnel must be out of OR. Due to the high contagiousness and viable nature of SARSCoV-2, no unnecessary items should be brought into the operating theater; this includes personal items, such as cell phones. Disposable caps and shoe covers should be worn and discarded after each case. Only the materials necessary for the case should be within the room, and all disposables should be discarded at the end of the case. Electrocautery of blood, gastrointestinal tissue, and any of the body fluids may generate an aerosol. An aspirator should remove smoke during surgery. All patient interactions will be performed with enhanced droplet precautions. For emergency operation on COVID-19 positive patients should be treated these as aerosol-generating procedures throughout the operative period (including intubation). Such cases should be performed with airborne precautions (N95 with face shield) and preferably in a negative pressure room.[11,16,50,51] All staff in the OR must use N95 or FFP2/FFP3 respirator, face mask (OR face shields/masks worn over N95), gown, gloves, hair cover, and shoe covers or plastic boots (Fig. 3a, b). If there is no suspicion of COVID-19, gowns may not be necessary for PPE saving, but droplet precautions must be taken. Patients who are asymptomatic, but contagious should be kept in mind. There is very little evidence regarding the relative risks of laparoscopy versus the conventional open approach, specific to COVID-19.[52] Although previous research has shown that laparoscopy may lead to aerosolization of blood-borne viruses, there is no evidence to indicate that this effect is seen with COVID-19.[53,54] The use of devices to filter released CO2 for aerosolized particles is strongly recommended for laparoscopic procedures.[55] An appropriate surgical approach should be chosen to minimize the duration of surgery and maximize safety for both patients and healthcare staff. 339


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8. Endoscopy

Conflict of Interest: None declared.

Urgent/emergent endoscopic procedures cannot be delayed. Upper and lower gastrointestinal bleeding or suspected bleeding leading to symptoms, dysphagia significantly impacting oral intake, cholangitis, or impending cholangitis that arises from common bile duct stone or periampullary tumor, palliation of upper or lower gastrointestinal obstruction are the most common emergent indications for endoscopy. Since patients can present with gastrointestinal manifestations of COVID-19, all endoscopic procedures performed in the current environment should be considered as high risk. For the patients with COVID-19, if there is an alternative method to replace endoscopy, such as transhepatic drainage of the biliary tract, it must be considered to avoid this high risk. The virus has been found in multiple cells in the gastrointestinal tract, and all fluids, including saliva, enteric contents, stool, and blood, use of surgical energy devices should be minimized.[55] For patients who are or may be infected, endoscopy should only be performed while wearing full PPE in a designated endoscopy room. Endoscopy procedures need short physical distance from patients to endoscopy staff. Based on studies performed during the SARS outbreak of 2003, droplets from infected patients could reach persons located 2 meters or more from the source.[19] All endoscopic interventions should only be performed in a way to resolve the urgent problem and completed as soon as possible to reduce the exposure risk and possible viral burden.

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

CONCLUSION Since the announcement of the first cases of COVID-19, the health care system, as in all areas of life, has also been trying to be adapting. To maintain the sustainability of the healthcare system, the protection of health-care providers should be the top priority. On the other hand, appropriate treatment should also be provided to patients requiring emergency health-care. To be able to do all this, hospitals should reorganize themselves, provide decent protective equipment to all staff, use the workforce effectively. Health-care professionals should also choose a treatment method appropriately in the circumstances to protect themselves and their patients as much as possible. In this paper, we try to summarize how these goals can be achieved for emergency surgery patients. As time goes on, we believe that our eyes will get used to the darkness that surrounds us, the research will illuminate our path, and the uncertainties about this insidious and invisible enemy will decrease. Until then, what needs to be done is to keep both health-care providers and their patients safe. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: M.E.; Design: A.F.K.G.; Supervision: M.M.Ö., M.H.K.; Fundings: A.F.K.G., M.E.; Materials: M.E.; Data: M.E., A.F.K.G.; Analysis: A.F.K.G., C.E.; Literature search: M.E., A.F.K.G.; Writing: A.F.K.G.; Critical revision: M.E., O.A. 340

REFERENCES 1. Lu H, Stratton CW, Tang YW. Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle. J Med Virol 2020;92:401–2. 2. Phelan AL, Katz R, Gostin LO. The Novel Coronavirus Originating in Wuhan, China: Challenges for Global Health Governance. JAMA. 2020 Jan 30. doi: 10.1001/jama.2020.1097. [Epub ahead of print] 3. Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis 2020;91:264–6. 4. WHO Director-General’s opening remarks at the media briefing on COVID-19 - 11 March 2020. Available from: https://www.who.int/ dg/speeches/detail/who-director-general-s-opening-remarks-at-themedia-briefing-on-covid-19---11-march-2020. Accessed April 12, 2020. 5. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA 2020;323:1239−42. 6. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054–62. 7. Borges do Nascimento IJ, Cacic N, Abdulazeem HM, von Groote TC, Jayarajah U, Weerasekara I, et al. Novel Coronavirus Infection (COVID-19) in Humans: A Scoping Review and Meta-Analysis. J Clin Med 2020;9:E941. 8. Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RTPCR. Euro Surveill 2020;25:2000045. 9. Zhao W, Zhong Z, Xie X, Yu Q, Liu J. Relation Between Chest CT Findings and Clinical Conditions of Coronavirus Disease (COVID-19) Pneumonia: A Multicenter Study. AJR Am J Roentgenol. 2020 Mar 3. doi: 10.2214/AJR.20.22976. [Epub ahead of print] 10. Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J, et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis 2020;20:425–34. 11. Karaca AS, Özmen MM, Uçar AD, Yastı AÇ, Demirer S. General Surgery Operating Room Practice in Patients with COVID-19. Turkish J Surg 2020;36:1–5. 12. Maintaining Trauma Center Access and Care during the COVID-19 Pandemic: Guidance Document for Trauma Medical Directors. Available from: https://www.facs.org/quality-programs/trauma/maintaining-access. Accessed April 4, 2020. 13. U.S Department of Defense (DoD). COVID-19 Practice Management Guide V10. Available from: https://health.mil/Reference-Center/Technical-Documents/2020/03/24/DoD-COVID-19-Practice-Management-Guide. Accessed April 16, 2020. 14. American College of Surgeons (ACS). COVID-19 Guidelines for Triage of Emergency General Surgery Patients. Available from: https://www. facs.org/covid-19/clinical-guidance/elective-case/emergency-surgery. Accessed April 16, 2020. 15. Robert Fojut. How trauma programs prepared for COVID-19. 2020. Available from: https://www.trauma-news.com/2020/04/how-trauma-

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DERLEME - ÖZET OLGU SUNUMU

COVID-19 pandemisi sırasında travma ve acil cerrahi uygulamaları için öneriler Dr. Ali Fuat Kaan Gök,1 Dr. Mehmet Eryılmaz,2 Dr. Mehmet Mahir Özmen,3 Dr. Orhan Alimoğlu,4 Dr. Cemalettin Ertekin,1 Dr. Mehmet Hamdi Kurtoğlu1 İstanbul Üniversitesi İstanbul Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul Sağlık Bilimleri Üniversitesi, Gülhane Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara İstinye Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul 4 İstanbul Medeniyet Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul 1 2 3

COVID-19, mevcut olan sınırlı bilgilere göre, yaşlılar ve yandaş hastalıkları olan her yaştan insan için ciddi problemler yaratabilecek yeni bir hastalıktır. Ayrıca, tüm yaş grupları da risk altındadır. Sağlık çalışanları, mesleklerinin doğası gereği her türlü enfeksiyona yakalanma riskine en çok maruz kalan profesyoneller olmuştur. Elektif cerrahiler COVID-19 hastalarına bakım vermek için ertelenmiştir. Bununla birlikte, travma cerrahisi, akut karın ve acil endoskopiler gibi bazı müdahaleler geciktirilemez. Sağlık sisteminin sürdürülebilirliğini korumak için sağlık çalışanlarının korunması en önemli konulardan birisidir. Öte yandan, acil sağlık hizmeti gerektiren hastalara da uygun tedavi sağlanmalıdır. Sağlık çalışanları, kendilerini ve hastalarını mümkün olduğunca koruyarak, en uygun tedavi yöntemini seçmelidir. Bu çalışma, COVID-19 pandemisi sırasında, bir cerrahın yapması gereken müdahale kaçınılmaz olduğunda nasıl uygun davranabileceğini özetlemeyi amaçlamaktadır. Anahtar sözcükler: Acil cerrahi; COVID-19; endoskopi; koronavirüs; travma. Ulus Travma Acil Cerrahi Derg 2020;26(3):335-342

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doi: 10.14744/tjtes.2020.79954

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EXPERIMENTAL STUDY

Effects of dabigatran and fondaparinux on degloving injuries: An experimental study Alper Ural, M.D., FEBOPRAS,1 Abdulkadir Yasir Bahar, M.D.,3 1

Fatma Bilgen, M.D.,1 Duygun Altıntaş Aykan, M.D.,2 Mehmet Bekerecioğlu, M.D.,1 Dilan Altıntaş Ural, M.D.4

Department of Plastic Reconstructive and Aesthetic Surgery, Kahramanmaraş Sütçü İmam University Faculty of Medicine,

Kahramanmaraş-Turkey 2

Department of Pharmacology, Kahramanmaraş Sütçü İmam University Faculty of Medicine, Kahramanmaraş-Turkey

3

Department of Pathology, Kahramanmaraş Sütçü İmam University Faculty of Medicine, Kahramanmaraş-Turkey

4

Department of Pediatric Surgery, Kahramanmaraş Sütçü İmam University Faculty of Medicine, Kahramanmaraş-Turkey

ABSTRACT BACKGROUND: Management of the skin degloving injuries is still a problematic issue, and the avulsed part of the skin may become necrotic. We hypothesized that the anticoagulant pharmacological agents, fondaparinux and dabigatran may be beneficial in the treatment of degloving injuries by enhancing the viability of the reattached flap. METHODS: Twenty four Wistar rats were divided into three groups as follows: control group (Group 1), fondaparinux group (Group 2) and dabigatran group (Group 3). A model of a degloving injury on the tail of rats was developed in all groups. After 15 minutes, the avulsed flaps were sutured back. Group 1 received 1ml/day saline intraperitoneally for 10 days. Group 2 received 0.3 ml/kg/day fondaparinux intraperitoneally for 10 days. Group 3 received 30 mg/kg/day dabigatran orally for 10 days. At the end of the treatments, gross morphological and histopathological tail tissue survivals were evaluated. RESULTS: Histopathological examination of the fondaparinux and dabigatran groups revealed that the tail skin was mostly viable with mild inflammation. The mean necrotic length in tails and severity of inflammation was significantly higher in the control group compared to the fondaparinux and dabigatran groups (p<0.05). No statistically significant differences were noted between the fondaparinux and dabigatran groups in histopathologic evaluations. There was no significant difference in necrosis lengths and the other histopathological parameters between dabigatran and fondaparinux groups. CONCLUSION: Dabigatran and fondaparinux improved tissue survival in skin degloving injuries concerning gross morphological and histopathological findings. However, the findings of this study should be supported and improved by new experimental and especially clinical studies. Keywords: Avulsion; degloving injury; flap; lower extremity reconstruction.

INTRODUCTION A degloving injury is a soft tissue injury defined as a traumatic avulsion of the skin and subcutaneous tissue, together with the underlying deep fascia. Dermal vascular plexus is included in the skin, and it is damaged due to the separation of vessels from the skin in degloving injuries. A degloving injury mostly occurs due to shear forces as a result of contact of the ex-

tremity with circling objects forming a high speed of friction, such as vehicle wheels or motorcycle accidents.[1] These injuries are divided into three patterns. Pattern 1 describes a pure degloving injury in which the underlying deep soft tissues are preserved. In pattern 2, deep soft tissues such as muscles and fascia, are also involved. Pattern 3 is the most severe type. It causes a degloving injury in the superficial skin

Cite this article as: Ural A, Bilgen F, Altıntaş Aykan D, Bahar AY, Bekerecioğlu M, Altıntaş Ural D. Effects of dabigatran and fondaparinux on degloving injuries: An experimental study. Ulus Travma Acil Cerrahi Derg 2020;26:343-350. Address for correspondence: Alper Ural, M.D. Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fak., Plastik Rekonstrüktif ve Estetik Cerrahi Anabilim Dalı, Kahramanmaraş, Turkey Tel: +90 344 - 300 36 49 E-mail: alper_ural@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(3):343-350 DOI: 10.14744/tjtes.2020.26678 Submitted: 24.01.2019 Accepted: 19.03.2020 Online: 13.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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and then continuously transfers into the deep soft tissues and even the bones, resulting in varying damages of soft tissue and different types of fractures.[2] The most common sites of degloving injuries are the extremities, especially the lower extremities, but these injuries may also occur in other regions of the body, such as the trunk and the cephalic region.[3] Mismanagement of such injuries results in delayed full-thickness necrosis of the avulsed skin flap and loss of the limb, or even worse, death.[4] Many strategies for management of degloving injuries have been proposed, including re-adaption of the flap, converting the avulsed flap into a graft, revascularizations or re-plantations as salvage, as well as the reconstruction with grafts, local flaps and free flaps.[5–7] Most studies related to degloving injuries in humans are composed of cross-sectional studies, descriptive studies or case reports. The use of pharmacological agents that are involved in coagulation may enhance the viability of the reattached flap with or without vascular anastomosis and may have beneficial effects on patients with degloving injuries. Dabigatran etexilate mesylate is an orally administered novel anticoagulant, which is a direct thrombin inhibitor.[8] Dabigatran prevents the conversion of fibrinogen to fibrin and thus inhibits thrombus formation.[9] Fondaparinux sodium is a new class of synthetic anticoagulant drugs that selectively bind and potentiate antithrombin III, thereby specifically inhibiting the factor Xa in the coagulation cascade.[10] We hypothesized that fondaparinux and the oral drug dabigatran, which have a similar mechanism of action in the coagulation cascade, may have beneficial effects on wound healing and improve the survival of avulsed skin in rat tails by facilitating microcirculation and preventing microthrombus formation. To our knowledge, there is no study that evaluated the effectiveness of these novel anticoagulants on degloving injuries. Hence, in this experimental study, we aimed to evaluate the efficiency of fondaparinux and dabigatran, novel antithrombotic agents, on degloving injuries in rats.

MATERIALS AND METHODS All experiments were conducted in strict accordance with the National Institute of Health Guidelines for the Care and Use of Laboratory Animals. The experimental procedures were performed in the Practice and Research Laboratory of Kahramanmaraş Sütçü Imam University. The protocols in this study were approved by the Local Committee on Animal Research Ethics (Ethics Committee File No: 2018/04, Approval date: 20.03.2018).

mg/kg/day in 1 ml of volume by oral gavage. The rats were anaesthetised by an intramuscular injection of 50 mg/kg of ketamine hydrochloride (Ketalar®; Pfizer, Istanbul, Turkey).

Study Groups Twenty-four male Wistar-albino rats with a body weight of 260–300 g each were equally and randomly divided into three groups (n=8 per group). The animals were kept in separate cages at an ambient temperature of 22°C and 60±5% humidity with a 12-hour light/dark cycle and ad libitum access to rat chow and water. The first group was the control group and administered 0.5 ml of saline once a day intraperitoneally (i.p.). In the second group, 0.3 mg/kg of fondaparinux was administered once a day i.p. for 10 days. In the third group, 30 mg/kg of dabigatran was administered daily by gastric gavage for 10 days. A model of a degloving injury on the tail of rats was developed in all groups. After 15 minutes, the avulsed tissues were sutured back. The colour of the skin and the status of the wound were examined daily for 10 days. During the studied period, no rats were excluded due to death or self-mutilation. At the end of the treatments, the rats were sacrificed by cervical dislocation.

Induction of Degloving Injury in Rats’ Tails The surgical method was based on the degloving injury model reported by Oztuna et al.[11] The skin and subcutaneous tissues were incised circumferentially 5 cm distal to the base of the tail. Subsequently, a moderate manual force was applied to the tail at the distal end of the incision using the thumb and index fingers. When a 4-cm-long avulsion of the skin and subcutaneous tissue from the underlying tendon and vascular tissue was achieved, the traction was ceased (Fig. 1). Fifteen minutes after the injury, the avulsed tissue was reapproximated and sutured back to its original position using 4/0 vicryl.

Evaluation of the Gross Morphologic and Histopathological Changes The lengths of the necrotic tail regions were measured in millimetres using a ruler. The circumferential lengths of necrosis

Drugs and Chemicals Fondaparinux (Aspen, France) 0.3 mg/kg/day was dissolved in 0.9% saline and administered intraperitoneally in 1 ml/kg of volume. Dabigatran (Boehringer Ingelheim, Germany) was mixed with drinking water and given orally to the rats by 30 344

Figure 1. Creation of a degloving injury site in the tail of the rats.

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(a)

(b)

(c)

Figure 2. (a) Intact epidermis in the dabigatran group. (b) Limited necrosis of the tail in the fondaparinux group. (c) Severe necrotic skin of the tail in the control group.

at the proximal and distal boundaries were measured. Warm, pink-white and pliable tissue was evaluated as viable skin, and brown-black, cold and hardened tissue was considered to be necrotic skin. For the histopathological examinations, the tissue samples were embedded in paraffin and sectioned in a longitudinal orientation, fixed in 10% neutral buffered formalin and stored in 5% formic acid. The tissues were followed by a Leica ASP 300 tissue processor device and sectioned at a thickness of 3 µm on a microtome (Leica RM 2145). The samples were stained with Haematoxylin-Eosin and examined via light microscopy by an experienced pathologist.

Data Analysis All data were recorded and analysed using SPSS for Windows v.15.0 (SPSS Inc., Chicago, IL, USA). Kruskal-Wallis H test was used for the statistical analysis of gross morphological and histopathological differences among the groups. Bonferroni correction was applied to correct for comparative differences. Comparisons in the 95% confidence interval and those that were found to have p-values of smaller than 0.05 were considered significant.

RESULTS Gross Morphologic Changes The avulsed tail flaps were cyanotic, and distal tail segments were oedematous in all animals on the postoperative day 2. We observed surgical wound infection in one rat in the saline group. Haematoma occurred only in one rat in the fondaparinux group. We also observed partial wound dehiscence of 3 mm in the tails of three rats, secondary to full-thickness necrosis in two rats in the control group, as well as one rat in the fondaparinux group. Skin necrosis was on a measurable level at the end of day 10. In the dabigatran and fondaparinux groups, six tails of each group healed well and showed limited necrosis (Fig. 2a, b), whereas a clear length of necrotic tails was observed in al-

most all of the rats in the control group (Fig. 2c). The mean length of the necrotic area was significantly higher in the saline group than the other groups (p=0.013). There were no statistically significant differences in the lengths of the necrotic area between the dabigatran and fondaparinux groups (Table 1).

Histopathological Results The clinical findings, histopathological findings and results of the statistical analysis demonstrated that the differences between the dabigatran and fondaparinux groups were not significant. There was a significant difference between the results of the control group and both the fondaparinux and dabigatran groups (Fig. 3). Kruskal Wallis test was used to determine whether the necrotic tissue length values changed for the three groups. According to the results of the test, there was a statistically significant difference between the mean values of necrotic tissue length among the three groups (p<0.05). Multiple comparison tests were performed to see the difference between the groups. According to the results of Bonferroni multiple comparisons, the necrotic tissue length in the saline group was significantly higher in comparison to the dabigatran and fondaparinux groups (p<0.05). The lowest necrotic tissue length was determined in the dabigatran group. While the p-value was 0.013 for the necrotic tissue length for the dabigatran and saline groups, there was no statistically significant difference between the fondaparinux and dabigatran groups. The severity of inflammation was evaluated using the Kruskal Wallis test for the three types of drugs. According to the results of the test, there was a statistically significant difference between the mean values of inflammation among the three groups (p<0.05). According to the results of the Bonferroni test, the severity of inflammation was significantly higher in the saline group in comparison to the fondaparinux and dabigatran groups (p<0.001). While the severity of inflammation

Table 1. The length of the necrosis (mean±SD) in the tails of rats Length of necrosis (mm)

Group 1 (Saline)

Group2 (Fondaparinux)

Group 3 (Dabigatran)

Mean±SD Mean±SD 48.5±6

23.5±8.03

Mean±SD 16.75±8.74

SD: Standard deviation.

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(a)

(b)

(c)

Figure 3. (a) In the dabigatran group, the epidermis was thinner than normal but not necrotic (marked with a star), and in the dermis, significant neovascularization and mild chronic active inflammatory infiltrate were observed (in the circle). (b) In the fondaparinux group, dermoepidermal blisters were seen on the surface, but no necrosis was observed, and the epidermis was intact (marked with a star). There were significant neovascularization and mild chronic inflammatory infiltrate in the dermis (in the circle). (c) In the control group, both the epidermis and papillary dermis were completely necrotic (in circle), and severe inflammation was also observed in the reticular dermis (inside the rectangle).

was determined in the saline group as the maximum, there was no statistically significant difference between the dabigatran and fondaparinux groups. To determine the neovascularization values, the Kruskal Wallis test was used. According to the results of the test, both fondaparinux and dabigatran groups showed significantly higher neovascularization in comparison to the saline group (p=0.011). There was no statistically significant difference between the fondaparinux and dabigatran groups. Although a better granulation tissue formation was seen in the dabigatran and fondaparinux groups in comparison to the saline group, the difference among the groups was not statistically significant (Figs. 4, 5). 450 400 350 300 250

DISCUSSION Degloving injuries are distinguished from other injuries by the damage in neurovascular structures that occurs together with trauma mechanisms. Vascular avulsion in the degloved skin results in necrosis due to impaired blood supply. A pure degloving injury is an avulsion with intact underlying anatomic structures, such as tendons, bones and joints. The skin and subcutaneous tissues are severely damaged and they are separated from the underlying fascia and muscles. Management of degloving injuries is challenging in both the upper and lower extremities. Degloving injury treatment is based on the viability of the avulsed skin flap and the site of the injury area. Depending on the type and severity of the degloving injury, various treatments may be performed including re-attachment of the flap, converting the avulsed flap into a full-thickness skin graft, reconstruction with splitthickness skin grafts, local or free flaps, revascularization and re-plantation.[6] There are several studies that provided satisfactory results in degloving injuries of the upper extremities thanks to microsurgical treatments like revascularization, venous anastomosis, arterial anastomosis or arterialisation by arteriovenous shunts.[12–17] Although there are no established guidelines or a consensus for the management of degloving injuries, the general treatment principles include preservation

200 150

25 20

100

15 10

50 0

Saline

Fondaparinux

Figure 4. Total necrotic lengths in the tails (mm).

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Dabigatran

5 0

Histopathological Results Fondaparinux Dabigatran Saline

Adhesion

Necrosis

Inflammation

Neovascularization

Granulation

Figure 5. Histopathological results in the groups.

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of as much tissue as possible, early primary definitive wound coverage, good-quality skin envelope and early functional recovery.[18] In fact, what makes management of degloving injuries so complex and involved is that the treatment options strictly change depending on the specific anatomy of the injury site, as well as its unique features. Hence, as a necessity, these cases must be evaluated with their own characteristics based on the trauma region. Latifi et al.[19] reported on the treatment options of degloving injuries by anatomical locations. The principal and best surgical treatment option in hand and finger degloving injuries is always replantation or revascularisation. Since avulsion of the blood vessels, consequently, the intimal damage may extend beyond the visible injury level; tissue viability should be examined meticulously. Nonetheless, the existence of other life-threatening injuries or crush injury of the degloved flap may not allow replantation.[18] When direct microsurgical anastomosis is not possible, the crossed arterial anastomosis technique and vein grafts, either for arterial repair or venous repair may be helpful in obtaining successful results. Because of the lack of an artery in degloved skin, repair of the hand using distally based skin flaps has been reported using arteriovenous shunting.[20] In such cases of hand degloving injuries, when a suitable artery could not be defined in the degloved flap for direct physiological revascularisation, radial artery to cephalic vein and/or superficial vein to digital artery arteriovenous anastomoses, in other words, arterialisation by creating arteriovenous fistulas, have been reported as reasonable salvage procedures in some cases.[21,22] Zhang et al.[23] recommended giving a survival chance for degloved hands and fingers by replantation or revascularization when the degloved skin is not severely damaged. However, they reported both the fingers and degloved flap following microsurgical repair were completely salvaged in only one of their patients. They suggested that, in the presence of diabetes mellitus, vascular diseases or heavy smoking history, microsurgical procedures require serious consideration. Lower limb and foot degloving injury management differs from upper extremity management with its complexity, since it requires different specialties.[19] Repositioning and suturing the flap back with or without microsurgical anastomosis, split-thickness skin grafting obtained from degloved flaps by defatting, dermal matrices, VAC (vacuum-assisted closure) or reconstruction with either flaps or grafts are the basic treatment modalities. Some authors agree that full-thickness skin graft conversion of the avulsed flap is the most appropriate choice in lower extremity degloving injuries since it is mostly not possible to identify a proper artery for anastomoses, or a proper artery in the degloved limb is often absent or traumatized. Moreover, vascular anastomoses are rarely successful for damaged skin flaps and contraindicated in most degloving injuries, especially Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

when degloved flaps are contused. When microsurgical repair is not feasible, replacement of avulsed skin flaps as full-thickness skin grafts may consistently provide satisfactory results in the treatment of degloving injuries in the lower extremities.[24] Hence, recently, the most frequently used technique in degloving injuries of the lower extremities is defatting the avulsed part and converting it into a full-thickness skin graft to cover the defect when revascularization is not possible. [2] Thereto, Chen and Liu[25] noted that preservation of the subcutaneous vascular network and adequate drainage might provide a better effect than split-thickness skin meshing and grafting alone. It is assumed that the golden time for degloving injury treatment is eight hours after injury because the initially avulsed flap has perfusion, but it then develops ischemia and necrosis due to circulation disorders as time goes by. The coagulation cascade reaction of damaged vascular endothelial cells alters the biological effects and blood coagulability. Since the inner walls of the blood vessels are very conducive to thrombosis, skin microcirculation worsens even further. As pointed out, in addition to the importance of anticoagulants after degloving injuries with or without microsurgical repair, they also play a major role in the survival of degloved flaps by decreasing the risk of thrombosis.[10,23] Herein, we utilized fondaparinux and dabigatran, since anticoagulation may have beneficial effects on wound healing and improve the survival of avulsed skin by facilitating microcirculation, preventing microthrombus formation and inhibition of coagulation cascade. Fondaparinux is a synthetic and selective inhibitor of the factor Xa that has proven efficacy and safety for preventing venous thromboembolism in orthopaedic surgery. In several recent studies, fondaparinux has been shown to be effective in preventing postoperative venous thromboembolism and venous congestion-associated flap failure.[25–27] Dabigatran, a novel anticoagulant, is a direct thrombin inhibitor that prevents the conversion of fibrinogen to fibrin and thus inhibits thrombus formation. Dabigatran has been approved by the FDA for the treatment of deep venous thrombosis and/or pulmonary embolism and venous thromboembolism prophylaxis. It has predictable pharmacokinetic and pharmacodynamic profiles, no known food interactions and no genetic metabolism variations.[28] The first rat model for degloving injuries was described by Oztuna et al.[11] in 2006. The authors induced a 3-cm-long avulsion injury in the tails of rats and examined the effects of pentoxifylline on the viability of avulsed flaps. In 2012, Milcheski et al.[29] described another degloving injury model in rat hindlimbs. They described four different types of hindlimb degloving injuries, including proximal flow pedicled flap, distal flow pedicled flap, lateral flow pedicled flap and medial flow pedicled flap. This animal model was used in a subsequent study to examine the effects of pentoxifylline and allopurinol on the viability of avulsed hindlimb flaps.[30] Although a hindlimb degloving injury model may seem to be more clinically relevant, it may be misleading while evaluating the re347


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sults. Once, during wound healing, plasmatic imbibition is expected to occur more in avulsed hindlimb flaps because of the relatively vascular nature of the underlying muscles. This condition may cause some part of the avulsed flap to be taken up as a graft by the underlying healthy vascular tissue. Compared to hindlimbs, the tissue underlying the avulsed flap in the tail is relatively more avascular, and hence, the probability of graft uptake is lower. Moreover, in a hindlimb degloving injury model, the avulsion of the flap is caused solely by traction using a towel clamp, and there is almost no crushing force applied to the tissues. However, while creating an avulsed flap in the tail degloving injury model, some force is also applied to the tissues by the thumb and the index finger. Therefore, while hindlimb and tail degloving injury models are both applicable to evaluate the avulsed skin as a defatted flap or a fullthickness graft, the tail degloving model mimics the clinical facts better concerning the trauma mechanism, and it is more reliable in determining the efficacy of drugs. We observed significant variability in the extent of flap necrosis in the tail degloving injury model when we compared our results with the results of the relevant studies in the literature. Demirtas et al.[31] examined the efficiency of hyperbaric oxygen therapy on healing in an experimental model of degloving injury in the tails of nicotine-treated rats and reported a necrosis length of 7.87±3.31 mm. Cebesoy et al.[32] encountered positive effects of both heparin and enoxaparin on the treatment of degloving injuries in rat tails, and they reported necrotic length as 10.2 mm. Azboy[33] evaluated the effects of the antithrombotic agents, enoxaparin and rivaroxaban, on tissue survival following skin degloving injury in an experimental rat tail model, and they reported a necrosis length of 14±5 mm in their control group. Altun et al.[34] compared the tail and hindlimb models in degloving injuries. They observed that the tail degloving injury model was a more reliable animal model for degloving injuries although the hindlimb degloving injury model may seem as if it was more clinically relevant. The extent of necrosis of tails in their study was higher with a length of 28.42±3.04 mm in comparison to those in previous studies. They explained this difference by the variability in the magnitude of the degloving force. We also observed a higher extent of necrosis in tails with a length of 16.75±8 mm in the dabigatran group and 48.5±6 mm in the saline group. In this study, even in the dabigatran group whose results were the best, the necrotic tail length measurements were longer than the results reported in similar studies in the literature. The most important reason that caused this difference is probably the length of the degloved tail. Although we implemented the model with a repeatable and standard force with the help of the preliminary studies before the experiment, another minor reason to encounter this difference may perhaps have been the variation in the magnitude of the force while leading to the degloving damage, as previously stated by Altun. Nonetheless, more importantly, the method in our study differed from the 348

aforementioned studies concerning the avulsion length created in the tail. The main reason for finding longer necrotic lengths was probably the creation of the degloving injury by avulsing the skin and subcutaneous tissue by 4 cm of length in the experimental model. The longer amount of avulsion while creating the degloving injury very likely caused us to obtain increased lengths of necrotic tails in all groups. This minor modification of the degloving injury model in the rat tail may be considered as a form of a mildly increased type 1 ring injury model, and it may also have caused the range of the numeric results of the treatments in this study to be broader. In our opinion, this minor modification in the experimental degloving model may also contribute to obtaining more comparable results with clinical practice. This study had some limitations. First of all, we did not use different doses of dabigatran and fondaparinux. We administered the doses based on previous experimental studies in the literature. Secondly, it is difficult to reproduce the same magnitude of manual force each time while leading to a skin degloving injury. However, preliminary experiments served us well to apply a more applicable and standard magnitude of the manual force in the experimental procedures. Nevertheless, it will be more beneficial to form a system or a device producing a standard magnitude of degloving force to avoid the variability in the groups. Since there were not any perforators of adequate calibre to repair the rat tail veins, we were not able to evaluate the effects of the drugs on perforasomes or a revascularized degloved flap. In a recent study by Kabakaş et al.,[35] although arterial perforator repair has been achieved, neighboring perforasomes have survived partially; however, the results of their study on degloving injuries seem promising for future studies. Therefore, to have a better understanding of this particular injury type and its effects on perforasomes, it will be necessary to develop new experimental degloving injury models allowing perforator repair and investigate the efficiency of pharmacological agents that can increase survival on these models. In our opinion, future experimental studies to focus on these recommendations will definitely make valuable contributions to degloving injury management. Moreover, we investigated the efficiency of dabigatran and fondaparinux only for the pattern 1 degloving injury model, which did not include deep soft tissues, bone fractures or any crush injury just like those without a completely diminished circulation. Therefore, the findings obtained in this experiment should not be considered valid for pattern 2 and pattern 3 degloving injuries. Finally, one should consider that the pharmacological agents used in this experiment showed significant efficacy in degloving injury, but these are not an alternative to replantation or revascularization. Depending on the findings of this experiment, these agents show beneficial effects and provide improvement in pattern 1 degloving injuries with adequate circulation in cases where any perforator repair is unavailable, or microsurgical revascularization cannot be performed. In conclusion, our findings suggest that fondaparinux and Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Ural et al. Effects of dabigatran and fondaparinux on degloving injuries

dabigatran had positive effects on preserving the viability of degloved rat tail skin flaps and contributed to limiting the progression of ischemia and necrosis. Fondaparinux and dabigatran significantly improved the survival rate in skin degloving injuries in a rat tail model. Based on the promising results obtained in this study, even in the absence of microsurgical repair, we believe that fondaparinux and dabigatran administration may be used as a supplementary treatment and provide beneficial effects for skin flap survival in degloving injuries. Further studies with different drug doses and study designs are required to assess whether or not these results may be applicable in humans, especially following arterial or venous repairs after degloving injuries.

Acknowledgements This study was supported by the Scientific Research Projects Coordination Unit of Kahramanmaraş Sütçü Imam University. Project number: 2018/4-21. Ethics Committee Approval: The experimental procedures were performed in the Practice and Research Laboratory of Kahramanmaraş Sütçü Imam University. The protocols in this study were approved by the Local Committee on Animal Research Ethics (Ethics Committee File No: 2018/04, Approval date: 20.03.2018). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.U.; Design: A.U.; Supervision: A.U., M.B.; Fundings: A.U., F.B., M.B., D.A.U.; Materials: A.U., F.B., A.Y.B., D.A.A., M.B.; Data: A.U., F.B., A.Y.B. D.A.A.; Analysis: A.U. F.B., D.A.U.; Literature search: A.U.,F.B.,M.B.; Writing: A.U., F.B., D.A.U.; Critical revision: A.U., F.B., D.A.U., M.B.; Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

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botic medication in skin surgery. Dermatol Surg 2012;38:1417–26. 9. Stangier J, Clemens A. Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Thromb Hemost 2009;15:9S–16S. 10. Büller HR, Davidson BL, Decousus H, Gallus A, Gent M, Piovella F, et al; Matisse Investigators. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial. Ann Intern Med 2004;140:867–73. 11. Oztuna V, Eskandari MM, Unal S, Colak M, Karabacak T. The effect of pentoxifylline in treatment of skin degloving injuries: an experimental study. Injury 2006;37:638–41. 12. Lo S, Lin YT, Lin CH, Wei FC. A new classification to aid the selection of revascularization techniques in major degloving injuries of the upper limb. Injury 2013;44:331–5. 13. Rodríguez-Lorenzo A, Lin CH, Lin CH, Ching WC, Lin YT. Replantation of a degloved hand with added arteriovenous anastomoses: report of two cases. J Hand Surg Am 2009;34:1864–7. 14. Boernert K, Ganot G, Ulrich MK, Iselin LD. Preserving the lower extremity after severe devolving injuries to meet the patient’s demand in two cases: (Limb salvage after degloving injury). Trauma Case Rep 2018;15:8–15. 15. Weinand C. Degloving Injuries of Upper Extremity: A Strategy with Full Thickness Skin Mesh. World J Plast Surg 2018;7:372–6. 16. Lin YH, Jeng CH, Hsieh CH, Lin HC. Salvage of the skin envelope in complex incomplete avulsion injury of thumb with venous arterializaiton: a case report. Microsurgery 2010;30:469–71. 17. Ju J, Li J, Hou R. Microsurgery in 46 cases with total hand degloving injury. Asian J Surg 2015;38:205–9. 18. Krishnamoorthy R, Karthikeyan G. Degloving injuries of the hand. Indian J Plast Surg 2011;44:227–36. 19. Latifi R, El-Hennawy H, El-Menyar A, Peralta R, Asim M, Consunji R, et al. The therapeutic challenges of degloving soft-tissue injuries. J Emerg Trauma Shock 2014;7:228–32. 20. Slattery P, Leung M, Slattery D. Microsurgical arterialization of degloving injuries of the upper limb. J Hand Surg Am 2012;37:825–31. 21. Chin T, Ono S, Hyakusoku H. Successful repair of flayed tissue in a degloving injury of the hand by arteriovenous anastomosis. J Plast Surg Hand Surg 2014;48:423−5. 22. Wang Y, Rui Y, Zhou J, Li F, Wu Y, Liu J. Successful repair of total hand degloving injury by avulsed skin in situ replantation through vascular transplantation: a case report. Ther Clin Risk Manag 2018;14:1429–33. 23. Zhang G, Ju J, Jin G, Tang L, Fu Y, Hou R. Replantation or revascularization for the treatment of hand degloving injuries. J Plast Reconstr Aesthet Surg 2016;69:1669–75. 24. Sakai G, Suzuki T, Hishikawa T, Shirai Y, Kurozumi T, Shindo M. Primary reattachment of avulsed skin flaps with negative pressure wound therapy in degloving injuries of the lower extremity. Injury 2017;48:137– 41. 25. Chen Y, Liu L. Clinical analysis of 54 cases of large area soft tissue avulsion in the lower limb. Chin J Traumatol 2016;19:337–41. 26. Reynolds NA, Perry CM, Scott LJ. Fondaparinux sodium: a review of its use in the prevention of venous thromboembolism following major orthopaedic surgery. Drugs 2004;64:1575–96. 27. Chung TL, Holton LH 3rd, Silverman RP. The effect of fondaparinux versus enoxaparin in the survival of a congested skin flap in a rabbit model. Ann Plast Surg 2006;56:312–5. 28. Schmitt AR, Zender CA, Bordeaux JS. A new oral anticoagulant in the setting of dermatologic surgery. J Am Acad Dermatol 2013;68:869–70. 29. Milcheski DA, Ferreira MC, Nakamoto HA, Tuma Jr P. Development of an experimental model of degloving injury in rats. [Article in Portuguese]. Rev Bras Cir Plast 2012;27:514–7. 30. Milcheski DA, Nakamoto HA, Tuma P Jr, Nóbrega L, Ferreira MC.

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33. Azboy I, Demirtaş A, Bulut M, Alabalik U, Uçar Y, Alemdar C. Effects of enoxaparin and rivaroxaban on tissue survival in skin degloving injury: an experimental study. Acta Orthop Traumatol Turc 2014;48:212–6. 34. Altun S, Orbay H, Ekinci M, Cetinbas A, Bal A, Arpaci E, et al. A comparison of rat degloving injury models. Acta Orthop Traumatol Turc 2017;51:308–12. 35. Kabakaş F, Özçelik İB, Mersa B, Dağdelen D, Aksakal İA, Özalp T. Perforator artery repair in revascularization of extremity degloving injuries. Injury 2019;50:S99–104.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Avülsiyon yaralanmalarında fondaparinuks ve dabigatranın etkileri: Deneysel bir çalışma Dr. Alper Ural,1 Dr. Fatma Bilgen,1 Dr. Duygun Altıntaş Aykan,2 Dr. Abdulkadir Yasir Bahar,3 Dr. Mehmet Bekerecioğlu,1 Dilan Altıntaş Ural4 Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Plastik Rekonstrüktif ve Estetik Cerrahi Anabilim Dalı, Kahramanmaraş Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, Kahramanmaraş Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Patoloji Anabilim Dalı, Kahramanmaraş 4 Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Çocuk Cerrahi Anabilim Dalı, Kahramanmaraş 1 2 3

AMAÇ: Avülsiyon yaralanmalarının yönetimi hala zorlayıcı bir konudur ve avülsiye olan deri flepleri nekroza uğrayabilmektedir. Antikoagülan ajanlar olan fondaparinuks ve dabigatran ile tedavi edilen avülsiyon yaralanmalarında tekrar yerine sütüre edilen fleplerin sağkalımını artırması hedeflenerek avülsiyon yaralanmalarının tedavisinde faydalı olabileceğini düşündük. GEREÇ VE YÖNTEM: Yirmi dört adet Wistar sıçanı üç gruba ayrıldı: Kontrol grubu (Grup 1), fondaparinuks grubu (Grup 2) ve dabigatran grubu (Grup 3). Tüm sıçanların kuyruğunda bir avülsiyon yaralanma oluşturulduktan 15 dakika sonra, avülsiyonlu dokular geri yerine sütüre edildi. Grup 1, 10 gün boyunca periton içine 1 ml/gün serum fizyolojik aldı. Grup 2, 10 gün boyunca periton içine 0.3 ml/kg/gün fondaparinuks aldı. Grup 3, 10 gün boyunca oral olarak 30 mg/kg/gün dabigatran aldı. Tedavilerin sonunda, morfolojik ve histopatolojik parametreler ve kuyruk doku sağkalımları değerlendirildi. BULGULAR: Histopatolojik incelemede fondaparinuks ve dabigatran gruplarında kuyruklarının çoğunluğunun sağlam kaldığı ve enflamasyonun ise hafif düzeyde olduğu gözlendi. Fondaparinuks ve dabigatran gruplarına göre kontrol grubunda ortalama kuyruk nekroz uzunluğu ve inflamasyonun şiddeti istatistiksel olarak daha yüksek bulundu (p<0.05). Dabigatran ve fondaparinuks grupları arasında nekrotik alanın uzunluğu ve diğer histopatolojik parametreler açısından anlamlı bir fark saptanmadı (p>0.05). TARTIŞMA: Dabigatran ve fondaparinuks, avülsiyon yaralanmasında morfolojik ve histopatolojik bulgular ile doku sağkalımını artırmıştır. Bununla birlikte, bu çalışmanın bulguları yeni deneysel çalışmalar ve özellikle klinik çalışmalar ile desteklenmeli ve geliştirilmelidir. Anahtar sözcükler: Alt ekstremite rekonstrüksiyonu; avülsiyon; flep. Ulus Travma Acil Cerrahi Derg 2020;26(3):343-350

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doi: 10.14744/tjtes.2020.26678

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EXPERIMENTAL STUDY

The protective effects of lycopene on ischemia/reperfusion injury in rat hind limb muscle model Mehmet Kirişçi, M.D.,1 Bülent Güneri, M.D.,2 Muhammed Seyithanoğlu, M.D.,3 Ülkü Kazancı, M.D.,4 Adem Doğaner, M.D.,5 Hakan Güneş, M.D.6 1

Department of Cardiovascular Surgery, Kahramanmaraş Sütçü İmam University Faculty of Medicine, Kahramanmaraş-Turkey

2

Department of Orthopedics and Traumatology, Kahramanmaraş Sütçü İmam University Faculty of Medicine, Kahramanmaraş-Turkey

3

Department of Medical Biochemistry, Kahramanmaraş Sütçü İmam University Faculty of Medicine, Kahramanmaraş-Turkey

4

Department of Medical Pathology, Kahramanmaraş Sütçü İmam University Faculty of Medicine, Kahramanmaraş-Turkey

5

Department of Biostatistics and Medical Informatics, Kahramanmaraş Sütçü İmam University Faculty of Medicine, Kahramanmaraş-Turkey

6

Department of Cardiology, Kahramanmaraş Sütçü İmam University Faculty of Medicine, Kahramanmaraş-Turkey

ABSTRACT BACKGROUND: Acute ischemia/reperfusion (I/R) injury of skeletal muscle, an important mortality and morbidity cause, is associated with oxidative stress. Lycopene is a carotenoid pigment with potent antioxidant activity and is found in vegetables and fruits. This study aims to investigate the protective effects of lycopene against I/R injury in rat hind limb muscle model. METHODS: Thirty-two Wistar-albino rats were randomly allocated to control, lycopene, I/R and I/R+lycopene groups. In lycopene and I/R+lycopene groups, the rats received 10 mg/kg/day lycopene orally for 15 days before the experiment. Dissection around abdominal aorta at the infrarenal level was performed in all rats under general anesthesia. The aorta was clamped at the infrarenal level in the I/R and I/R+lycopene groups for two hours. Then, reperfusion was allowed for two hours in these groups. Samples were obtained from the hind limb muscles of rats after sacrifice for biochemical and histopathological analyses. RESULTS: Serum and tissue malondialdehyde and ischemia-modified albumin levels were significantly lower in the I/R+lycopene group compared to I/R group (p<0.001). Serum glutathione peroxidase (GSH-Px) levels were significantly lower in the I/R group compared to those in control and I/R+lycopene groups (p<0.05). Tissue GSH-Px levels were significantly lower in the I/R group compared to the Lycopene group (p=0.003). Serum superoxide dismutase (SOD) levels were significantly lower in the I/R group compared to three groups (p<0.001). Tissue SOD levels were significantly lower in the I/R group compared to those in control and Lycopene groups (p=0.005). Histopathological assessments revealed that inflammatory changes following I/R injury were significantly reduced in the I/ R+lycopene group. CONCLUSION: The findings obtained in this study show lycopene’s cytoprotective activity against I/R injury in rat skeletal muscle model. Keywords: Antioxidants; ischemia; lycopene; reperfusion injury; tourniquets.

INTRODUCTION Skeletal muscle tissue is relatively resistant to ischemia compared to other tissues.[1] Acute ischemia/reperfusion (I/R) injury of limb skeletal muscle, which arises from various mechanisms, is an important cause of mortality and morbidity.[2,3]

Thrombosis and embolism are the leading causes of acute limb ischemia.[4] In addition, many events, such as abdominal aortic surgery, free-flap reconstruction procedures, trauma, surgical revascularization of limbs, and various orthopedic procedures with tourniquet use, may be associated with I/R injury.[5–8] The skeletal muscle I/R injury initially leads to the

Cite this article as: Kirişçi M, Güneri B, Seyithanoğlu M, Kazancı Ü, Doğaner A, Güneş H. The protective effects of lycopene on ischemia/ reperfusion injury in rat hind limb muscle model. Ulus Travma Acil Cerrahi Derg 2020;26:351-360. Address for correspondence: Bülent Güneri, M.D. Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Kahramanmaraş, Turkey Tel: +90 344 - 300 33 78 E-mail: bulentguneri@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(3):351-360 DOI: 10.14744/tjtes.2020.81456 Submitted: 12.06.2019 Accepted: 30.03.2020 Online: 14.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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loss of contractile function of the muscles. Severe cases of I/R injury may result in the loss of the limb or death. Reperfusion of tissues following a period of ischemia, which is essential for the viability of tissues, causes further damage by inducing both systemic and local inflammatory responses. Systemic inflammatory responses may lead to remote organ injury or multiple organ failure.[9] Diffuse microvascular dysfunction and alterations in tissue barrier function may occur in association with inflammation.[10] The skeletal muscle I/R injury is associated with oxidative stress as well. Biochemical reactions, activated by the skeletal muscle I/R injury, primarily lead to the loss in the supply of energy of the muscle resulting in endothelial dysfunction and neutrophil sequestration, which are followed by the formation of reactive oxygen species (ROS). ROS include free oxygen radicals, such as superoxide anion radicals and hydroxyl radicals. ROS attack lipids in the cell membrane and induce lipid peroxidation. Furthermore, ROS may affect cellular proteins, lipids, nucleic acids and other potentially sensitive substances. [11,12] Defensive antioxidant mechanisms, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), are activated in response to the formation of such noxious oxidative substances. These enzymes catalyze the transformation of ROS into less reactive species and protect the human body from the noxious effects of ROS and free radicals. Lipid peroxidation of cell membranes associated with I/R injury may lead to cell death. The alteration also occurs in the levels of malondialdehyde (MDA), an indicator of lipid peroxidation. [13] Ischemia-modified albumin (IMA) assay – also known as albumin cobalt binding assay – is another biomarker for tissue ischemia. In the I/R, acidosis and formation of free oxygen radicals may induce changes in binding capacity of albumin for cobalt.[14] Various treatment strategies and studies on antioxidant vitamins, bioflavonoids and medicinal products aim to reduce injury associated with I/R.[15,16] Lycopene is a carotenoid pigment found in vegetables and fruits, particularly in tomatoes, watermelons, pink grapefruits and pink guavas. Among dietary carotenoids, lycopene is the most potent antioxidant, anti-cancer and anti-inflammatory agent.[17–19] Furthermore, lycopene has a protective effect against skin apoptosis resulting from ultraviolet rays.[20] Antiinflammatory and antioxidant activities of lycopene have been considered to be responsible for its beneficial effects.[21,22] Lycopene has long since been safely taken through dietary sources, including vegetables and fruits. Studies in rats have failed to demonstrate any teratogenic effects of lycopene storage in the plasma, on the liver or any other tissues.[23,24] In this study, we aimed to investigate the antioxidative activity of lycopene against I/R injury in skeletal muscles of the hind limbs in rats.

MATERIALS AND METHODS A total of 32 adult male Wistar-albino rats, weighing 200–250 352

g, were used in this study. The rats were housed and maintained at 22 degrees Celsius, 60±5% humidity and a 12-h light-dark cycle with free access to food and water ad libitum. After this study was approved by the laboratory animals local ethics committee, this study was conducted in the animal experiments laboratory of the institution. All experimental procedures were performed according to the principles of laboratory animal care and use.

Study Design and Experimental Procedures The rats were randomly allocated to four groups as follows: control group, lycopene (Lyc) group, I/R group, and I/R+lycopene (I/R+Lyc) group. Therefore, each group contained eight rats. In the Lyc group and I/R + Lyc group, the rats received 10 mg/kg/day lycopene (Redivivo Lyc 10%; CWS/TG, Basel, Switzerland) with oral gavage for 15 days before the experimental procedure. All animals were anesthetized with ketamine hydrochloride (Ketalar 50 mg/kg i.m., ParkeDavis, Eczacıbaşı, Istanbul, Turkey). During the procedures, additional ketamine hydrochloride was applied intramuscularly as needed. The surgical procedures were performed to the rats laid in a supine position under a heating light. The skin was shaved, cleansed with antiseptic solutions, and a midline laparotomy was performed in each rat. Dissection around abdominal aorta at the infrarenal level was carried out in all rats. The abdominal aortae were clamped using atraumatic microvascular clamps (Micro DeBakey Bulldog Clamp, Biomedical Research Instruments, Malden, MA, USA) at the infrarenal level in the rats allocated to I/R and I/ R+Lyc groups, to induce hind limb ischemia. The distal flow was checked to ascertain the cessation of flow after clamping. The abdominal were closed using surgical towel clamps (Backhaus Towel Clamp, Bahadir Medical Instruments, Samsun, Turkey) after abdominal laparotomy, and dressings were used to maintain the temperature and hydration in these rats. After 120 minutes of ischemia, microvascular clamps were removed to allow reperfusion of hind limbs for 120 minutes. After the completion of reperfusion, the rats were sacrificed under anesthesia. In control and Lyc groups, rats were sacrificed after laparotomy without producing I/R injury. Blood and muscle tissue samples were obtained from all animals for biochemical and histopathological analyses.

Biochemical Assessments All blood samples obtained from the rats at the end of the experimental procedures were centrifuged at 3000 rpm for 10 minutes to separate the plasma. The plasma and muscle tissue samples were stored at -80 degrees Celsius until the time of analysis. The samples were thawed on the day of the analysis. The muscle tissues were homogenized in ice-cold 0.15 Molar (M) KCl (10%, w/v). The tissue homogenates were centrifuged at 4 degrees Celsius for 10 minutes at 600xg to separate crude fractions. Subsequently, supernatants were centrifuged for 20 minutes at 10,000xg to obtain the postmitochondrial fraction. Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Kirişçi et al. The protective effects of lycopene on I/R injury in rat hind limb muscle model

GSH-Px, SOD, MDA, and IMA levels were measured as markers of oxidative stress. SOD and GSH-Px activities were measured in post-mitochondrial fractions of muscle tissue samples. MDA levels were measured in tissue homogenates. Serum and tissue MDA levels were assayed using thiobarbituric acid according to the method of Buege and Aust.[25] 0.5 mL distilled water was added to tubes containing 0.5 mL serum or tissue homogenate. 2 mL of Buege separator was added (15 w/v trichloroacetic acid, 0.375 w/v% thiobarbituric acid and 0.25 mol/l hydrochloric acid solution mixed in equal volumes) to the mixture. The tubes containing the mixture were boiled in a boiling water bath for 15 minutes. After cooling, the precipitate was centrifuged at 4000 rpm for 10 minutes. The absorbance of the samples was determined by spectrophotometric method at 535 nm. The SOD activity was determined using Beyer and Fridovich’s methodology. Accordingly, to obtain superoxide radicals reacting with 2-(4-iodophenyl)-3-(4-nitrophenol-s phenyltetrazolium chloride) to yield red formazan stain, xanthine and xanthine oxidase were used. Then, SOD activity was measured by the extent of inhibition of this reaction.[26] The GSH-Px activity was measured using the method of Paglia and Valentine with cumenehydroperoxide as a substrate. In this method, GSH-Px activity was coupled to the oxidation of NADPH by glutathione reductase and the oxidation of NADPH was followed spectrophotometrically at 340 nm at 37 degrees Celsius. Results were calculated using the extinction coefficient (6.22×103/M cm).[27] Serum IMA levels were measured spectrophotometrically using the colorimetric method developed by Bar et al.[14] 10 µl of 1 g/l cobalt chloride solution was added to 40 µl of the serum, mixed and allowed to incubate for 10 minutes at room temperature. Then, 10 µl of a 1.5 g/l DTT solution was added and mixed. Incubated for two more minutes at room temperature, 200 µl of a 9.0 g/l solution of NaCl was added. Specimen blinds were similarly prepared without the addition of

the DTT. The absorbance of the test mixtures was detected at 470 nm. The results were evaluated in absorbance units.

Histopathological Assessments The muscle tissues surgically excised for histopathological studies were immediately fixed in 10% neutral formalin solution. Fixed tissue samples were embedded in paraffin and cut into serial sections with equal intervals. Each slide was stained with hematoxylin-eosin and examined and photographed under a light microscope (Nikon, Tokyo, Japan, 10x). Rat muscles were rated for histopathological assessment. A semi-quantitative histological analysis was performed to rate atrophy, peripheral location of nuclei, findings of perivascular inflammation or focal central muscle necrosis to define muscle breakdown using the light microscope: grade 0/ normal, grade 1/mild, grade 2/moderate, and grade 3/severe.

Statistical Analyses The normal distribution of the study data was evaluated using the Shapiro-Wilk test. The difference between the groups for variables with normal distribution was tested with oneway analysis of variance (ANOVA). For post-hoc pairwise comparisons, Tukey HSD, Tamhane T2, and Dunnett tests were used. Statistical parameters were expressed as mean ± standard deviation. A p-value of less than 0.05 was considered significant. The results were also expressed in tables and figures. Data analysis was performed using IBM SPSS V 22.0 (IMB Corporation, Armonk, New York, United States) software pack.

RESULTS The analyses of muscle tissue and serum test results revealed statistically significant intergroup differences (Tables 1 and 2).

Serum Biochemistry Results Significant intergroup differences were detected in the mean serum GSH-Px values; control group (136.56±14.77), Lyc group (124.27±35.48), I/R group (105.63±13.39), and I/R+Lyc

Table 1. The serum biochemical analyses GSH-Px nmol/mL

Control Lycopene

I/R

I/R+Lycopene F

p

Mean±SD Mean±SD Mean±SD Mean±SD 136.56±14.77c 124.27±35.48 105.63±13.39a,d 147.01±28.35c 3.463 0.033*

MDA nmol/mL

23.53±4.22c 25.53±4.85c 54.57±13.62a,b,d 28.33±3.77c 25.679 <0.001*

SOD U/mL

1.91±0.14c,d 1.83±0.15c,d 1.11±0.05a,b,d 1.44±0.16a,b,c 54.681 <0.001*

IMA abs/U

0.44±0.02c 0.45±0.01c 0.50±0.03a,b,d 0.42±0.04c 15.112 <0.001*

One-way Anova; Post-hoc: the Tukey HSD test; the Tamhane T2 test; the Dunnett test; α: 0.05; *The difference is statistically significant; aStatistically significant difference when compared the control group; bStatistically significant difference when compared to the lycopene group; cStatistically significant difference when compared to the I/R group; dStatistically significant difference when compared to the I/R + Lycopene group. Superscript letters denote significant differences (p<0.05). GSH-Px: Glutathione peroxidase; IMA: Ischemia modified albumin; I/R: Ischemia/reperfusion; MDA: Malondialdehyde; SOD: Superoxide dismutase; SD: Standard deviation.

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Table 2. The muscle tissue biochemical analyses

Control Lycopene

I/R

I/R+Lycopene F

p

Mean±SD Mean±SD Mean±SD Mean±SD 202.09±18.19c 123.03±19.18b 168.77±49.10 6.038 0.003*

GSH-Px nmol/mL

159.16±49.97

MDA nmol/mL

92.25±6.74 86.06±9.54c,d 126.94±18.22a,b,d 37.50±25.81a,b,c 38.239 0.001*

SOD U/mL

35.69±12.03c 40.23±5.24c 23.86±4.25a,b 33.75±9.82 5.325 0.005*

c,d

One-way Anova; Post-hoc: the Tukey HSD test; the Tamhane T2 test; the Dunnett test; α: 0.05; *The difference is statistically significant; aStatistically significant difference when compared the control group; bStatistically significant difference when compared to the study drug group; cStatistically significant difference when compared to the I/R group; dStatistically significant difference when compared to the I/R+ study drug group. Superscript letters denote significant differences (p<0.05). GSH-Px: Glutathione peroxidase; IMA: Ischemia modified albumin; I/R: Ischemia/reperfusion; MDA: Malondialdehyde; SOD: Superoxide dismutase; SD: Standard deviation.

Significant intergroup differences were detected in the mean serum SOD values; control group (1.91±0.14), Lyc group (1.83±0.15), I/R group (1.11±0.05), and I/R+Lyc group (1.44±0.16) (Fig. 3). No significant differences were found between control and Lyc groups. When compared to other groups, the mean serum SOD levels were significantly lower in the IR group (p<0.001). The comparison between the I/ R+Lyc and I/R groups revealed that the mean serum SOD lev-

els were significantly higher in the I/R+Lyc group. The mean serum SOD levels were significantly lower in the I/R+Lyc group compared to control and Lyc groups (p<0.001). Intergroup comparisons of the mean serum IMA levels revealed significant differences between I/R group and other Serum 60.00 50.00 MDA nmol/mL

group (147.01±28.35) (Fig. 1). No significant differences were found between control and Lyc groups. When compared to I/R+Lyc group and control group, the mean serum GSH-Px levels were significantly lower in the I/R group (p<0.05). The mean serum GSH-Px levels were significantly higher in the I/ R+Lyc group compared to I/R group (p<0.05). Significant differences were detected between I/R group and other groups in the mean serum MDA values; control group (23.53±4.22), Lyc group (25.53±4.85), I/R group (54.57±13.62), and I/R+Lyc group (28.33±3.77) (Fig. 2). The mean serum MDA values were statistically significantly higher in the I/R group compared to the other three groups (p<0.001). No significant differences were found among the other three groups.

40.00 30.00 20.00 10.00 0.00

Control

Lycopene

I/R

Lycopene+I/R

Figure 2. Intergroup comparisons of the serum malondialdehyde (MDA) levels.

Serum Serum

200.00 2.00

1.50 SOD Ul/mL

GPX nmol/mL

150.00

100.00

50.00

0.00

0.50

Control

Lycopene

I/R

Lycopene+I/R

Figure 1. Intergroup comparisons of the serum glutathione peroxidase (GPX) levels.

354

1.00

0.00

Control

Lycopene

I/R

Lycopene+I/R

Figure 3. Intergroup comparisons of the serum superoxide dismutase (SOD) levels.

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groups; control group (0.44±0.02), Lyc group (0.45±0.01), I/R group (0.50±0.03), and I/R+Lyc group (0.42±0.04) (Fig. 4). The mean serum IMA levels were statistically significantly higher in the I/R group compared to the other three groups (p<0.001). No significant differences were found among the other three groups.

Muscle Tissue Biochemistry Results Intergroup comparisons of the mean muscle tissue GSH-Px levels revealed that the levels in the I/R group were statistically significant lower than those in Lyc group while no significant differences were found among other groups (p<0.05); control group (159.16± 49.97), Lyc group (202.09±18.19), I/R group (123.03±19.18), and I/R+Lyc group (168.77±49.10) (Fig. 5). Intergroup comparisons of the mean muscle tissue MDA levels revealed significant differences; control group (92.25±6.74), Lyc group (86.06±9.54), I/R group (126.94±18.22), and I/ R+Lyc group (37.50±25.81) (Fig. 6). No significant differences were found between control and Lyc groups. The mean tissue MDA levels in the I/R group were statistically significantly higher compared to the levels in other groups (p<0.001). The Serum

mean tissue MDA levels in the I/R+Lyc group were significantly lower compared to the levels in other groups (p<0.001). Intergroup comparisons of the mean muscle tissue SOD levels revealed that the mean enzyme levels were significantly lower in the I/R group compared to control and Lyc groups (p<0.001). The mean tissue SOD levels in the I/R+Lyc groups did not significantly differ from the levels in other groups; control group (35.69±12.03), Lyc group (40.23±5.24), I/R group (23.86±4.25), and I/R+Lyc group (33.75±9.82) (Fig. 7).

Histopathological Results Histopathological assessment of skeletal muscles was rated using the light microscope concerning atrophy, peripheral location of nuclei, signs of perivascular inflammation, and focal central muscle necrosis. Intergroup differences were assessed based on this rating (Table 3). In the histopathological assessment of skeletal muscles, atrophy was not observed in rats from control and Lyc groups while nuclei were peripherally located. Neither signs of perivascular inflammation nor focal central muscle necrosis were observed in these groups. Grade 1 atrophy was detected in the I/R group, while atrophy was significantly reduced in the I/R+Lyc group (p<0.001). Nuclei were peripherally located in the samples from con-

0.60

Muscle 150.00

0.40 MDA nmol/mL

IMA abs/U

0.50

0.30 0.20

100.00

50.00

0.10 0.00

Control

Lycopene

I/R

0.00

Lycopene+I/R

Figure 4. Intergroup comparisons of the serum (ischemia-modified albumin) IMA levels.

Control

Lycopene+I/R

Muscle

250.00

0.50

200.00

0.40 SOD U/mL

GPX nmol/mL

I/R

Figure 6. Intergroup comparisons of the muscle tissue malondialdehyde (MDA) levels.

Muscle

150.00 100.00 50.00 0.00

Lycopene

0.30 0.20 0.10

Control

Lycopene

I/R

Lycopene+I/R

Figure 5. Intergroup comparisons of the muscle tissue glutathione peroxidase (GPX) levels.

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0.00

Control

Lycopene

I/R

Lycopene+I/R

Figure 7. Intergroup comparisons of the muscle tissue superoxide dismutase (SOD) levels.

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Kirişçi et al. The protective effects of lycopene on I/R injury in rat hind limb muscle model

Table 3. The intergroup comparisons regarding grading of the tissue specimens by histological evaluation Histological findings in tissue specimens

Grading by Control I/R group histological group (n=8) evaluation (n=8)

Lycopene group (n=8)

I/R+Lycopene group (n=8)

X2 p

Atrophy

Grade 0

8

0

7

7

28.486

Grade 1

0

8

1

1

Grade 2

0

0

0

0

Grade 3

0

0

0

0

Peripherally located

Grade 0

0

0

0

0

nuclei

Grade 1

0

0

0

0

22.154

Grade 2

0

6

0

0

Grade 3

8

2

8

8

Signs of perivascular

Grade 0

8

0

8

4

inflammation

Grade 1

0

0

0

3

33.778

Grade 2

0

4

0

1

Grade 3

0

4

0

0

Focal central muscular

Grade 0

8

0

6

2

necrosis

Grade 1

0

4

2

6

28.667

Grade 2

0

4

0

0

Grade 3

0

0

0

0

<0.001*

<0.001*

<0.001*

0.001*

Exact test; α: 0.05. *Statistically significant intergroup difference was detected in the distribution of variables. I/R: Ischemia/reperfusion.

trol, Lyc, and I/R+Lyc groups, while the peripheral location of nuclei was altered in the I/R group (p<0.001). Perivascular infiltration was not observed in control and Lyc groups; however, the number of perivascular inflammatory cells was remarkable in the I/R group (p<0.001). Perivascular inflammation significantly reduced but persisted in the I/R+Lyc group compared to the control group. A moderate-intensity focal central muscular necrosis was observed in the I/R group. Focal central muscular necrosis significantly reduced in the I/ R+Lyc group compared to the I/R group (Figs. 8–11).

In oxidative stress, the balance between the antioxidant mechanism and free radicals in the cell and body system disappears. I/R injury of skeletal muscle, a condition of oxidative stress resulting from vascular or traumatic injuries, may cause a series of events, including severe cellular and organ dysfunctions.[28,29] I/R injury induces biochemical events, which result in depletion of energy supplies of muscles, endothelial dysfunction, neutrophil sequestration and eventual ROS forma-

Figure 8. Histopathological assessment of the control group. Regular sarcoplasm and peripheral nuclei are seen in this tissue sample.

Figure 9. Histopathological assessment of the lycopene group. Regular sarcoplasm, peripheral nuclei and signs of mild atrophy (encircled) are seen in this tissue sample.

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DISCUSSION

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tion: two treatment groups (resveratrol in 0.5% ethyl alcohol administration before tourniquet release with four-hour and eight-hour reperfusion) and two control groups (0.5% ethyl alcohol administration before tourniquet release with fourhour and eight-hour reperfusion). The MDA levels, as well as polymorphonuclear leukocyte infiltration, edema, change in muscle fiber diameter and segmental necrosis, were less in treatment groups than those in control groups. Concerning these findings, the authors mentioned the protective effects of resveratrol against I/R injury in striated muscles following tourniquet application.

Figure 10. Histopathological assessment of the ischemia-reperfusion group. Focal central muscular necrosis and signs of mild atrophy (encircled) are seen in this tissue sample.

Figure 11. Histopathological assessment of the ischemia-reperfusion+lycopene group. Sparse necrosis is seen in this tissue sample.

tion.[11,12] Granulocytes and macrophages, along with humoral factors, including complements and coagulation factors, contribute to the injury. ROS are potent oxidizing and reducing agents which damage cell membranes by lipid peroxidation and lead to the activation of neutrophils.[30] These molecules have been considered to play an important role in the tissue damage associated with I/R injury. The entry of a high number of leukocytes into extracellular space immediately after reperfusion is particularly associated with the release of huge amounts of ROS, which is likely to overcome cellular antioxidant defenses. The frontline defenders battling against oxygen radicals include the enzymes SOD and GSH-Px. Various natural substances have been tested for restriction or prevention of ROS induced I/R injury. Elmali et al.[31] studied the effects of resveratrol, a phytoalexin produced by several plants, in striated muscle of hind limb of 24 Sprague-Dawley rats regarding I/R injury. Their study included four groups all of which featured tourniquet applicaUlus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

Ozyurt et al.[32] investigated the preventive effects of caffeic acid phenethyl ester (CAPE), a component of propolis, on I/R injury induced in rat hind limbs. Their study included four groups (sham, I/R, I/R+CAPE and I/R+vitamin E) in which rats were exposed to single-limb ischemia and reperfusion, each stage lasting two hours. CAPE and vitamin E were administered one hour after the onset of ischemia. The results of two treatment groups (I/R+CAPE and I/R+vitamin E) indicated lower MDA and NO levels in plasma and muscle compared to I/R group. No difference was noted concerning muscle tissue SOD activity in three groups, but plasma SOD activity was greater in two treatment groups compared to I/R group. In view of these findings, the authors stressed the benefits of CAPE administration which had also been mentioned to be comparable to those of vitamin E. Distinct from the aforementioned studies studying natural substances, Koca et al.[33] investigated the effects of hyperbaric oxygen and ozone treatment before the induction of I/R injury concerning oxidative/nitrosative stress. The authors reported an increase in tissue MDA levels, tissue SOD activity, serum nitrite-nitrate levels and decrease in tissue GSH-Px activity in the I/R group. Unlike I/R group, a decrease in MDA and nitrite-nitrate tissue levels and increase in tissue GSH-Px activity were detected in both I/R+hyperbaric oxygen and I/ R+ozone groups. SOD activity was found to be increased in the I/R+ozone group while the change in the I/R+hyperbaric oxygen group was insignificant. Tissue essays by inducible nitric oxide synthase staining demonstrated fewer changes in the I/R+ozone and I/R+hyperbaric oxygen groups compared to I/R group. The results of this study indicated the protective features of hyperbaric oxygen and ozone treatment against I/R injury in rat skeletal muscle. Lycopene, a carotenoid compound abundantly found in red fruits, has potent antioxidative properties as well. It has been studied in various tissues other than skeletal muscle concerning I/R injury restriction or prevention. In a study of experimental renal I/R injury, Kaya et al.[34] orally administered 100 mg/kg of lycopene to rats six hours before the procedure. Both renal arteries were clamped for 45 minutes to create ischemia. After that, the clamps were removed and the kidneys were reperfused for six hours. Tissue and serum samples were collected to measure MDA, glutathione (GSH), urea 357


Kirişçi et al. The protective effects of lycopene on I/R injury in rat hind limb muscle model

(BUN) and creatinine. Based on the study results, a significant decrease was detected in BUN, MDA and creatinine levels while an increase in GSH levels was observed in the group receiving lycopene. The results from this study demonstrate that lycopene has protective effects on renal tissue against I/R injury. In an experimental study conducted by Hua et al.,[35] spinal cord ischemia was induced by cyclooxygenase-2 (cox-2) suppression. Lycopene was administered for 14 days following cox-2 suppression. The reduction was observed in neuroinflammation and neuronal cell death in tissue and blood samples collected at the end of 14 days of treatment. Furthermore, Hua et al. demonstrated that increased cox-2, nuclear factor-κB, activated protein-1 and reduced heme oxygenase-1 levels, which were induced by spinal cord ischemia, could also be restored to normal by lycopene. Therefore, the relevant study indicated the neuroprotective activity of lycopene. Bansal et al.[36] administered lycopene to rats for 31 days at a dose of 1 mg/kg daily. Subsequently, they induced myocardial I/R by creating ischemia for 45 minutes and reperfusion for one hour in an experimental study. Serum samples were collected and MDA, SOD and GSH-Px levels were measured. MDA levels were found to be statistically significantly higher in the I/R group compared to the control group, while a statistically significant decline was observed in MDA levels in the group receiving lycopene. When compared to the control group, a statistically significant decline was observed in SOD and GSH-Px levels in the I/R group while a non-significant increase was detected in SOD levels and a statistically significant increase was detected in GSH-Px levels in the group receiving lycopene. Lower SOD and GSH-Px levels, detected following I/R, suggested that antioxidant enzyme activity had probably been inhibited due to intensive oxidative stress. When compared to I/R group, higher enzyme levels associated with the antioxidative effects of lycopene revealed its protective effects against oxidative stress. In the I/R+Lyc group of the present study, a significant decrease was observed in the serum and tissue MDA levels, as well as the serum IMA levels, compared to the I/R group, indicating significant increase due to overwhelming oxidative stress in the latter group and antioxidative effects of lycopene in the former group. The low mean levels of tissue MDA relative to the mean levels of serum MDA in the I/R+Lyc group can be explained with the likely superior potency of lycopene on hampering MDA formation in skeletal muscle compared to serum. The mean tissue and serum levels of antioxidant enzymes (i.e., GSH-Px and SOD) utilized to measure oxidative stress were significantly suppressed in the I/R group. Besides, the mean serum levels of the antioxidant enzymes in the I/R+Lyc group were remarkably higher than those in the I/R group, an additional indicator of the protective effects of lycopene against I/R injury. However, the mean tissue levels of the enzymes 358

were relatively high in the I/R+Lyc group without statistical significance in comparison to the tissue levels in the I/R group. These differences regarding the comparisons of mean tissue and serum levels of antioxidant enzymes can be attributed to the duration of ischemia and reperfusion stages of this study (i.e., 120 minutes for each stage). Other explanations for the difference of the biochemical parameters between the muscle tissue and serum are the chain reaction nature of oxidative processes (i.e., one process can potentiate another) and the differences between the reactions of skeletal muscle and serum to the antioxidative effects of lycopene.[37] Histopathological examination of the muscle tissue specimens by light microscopy reveals considerable tissue damage in the I/R group compared to I/R+Lyc group in which atrophy, perivascular inflammation, and focal central muscular necrosis were decreased while peripheral positioning of the nuclei was maintained. Concerning biochemical and histopathological findings of the present study, we suggest that dietary intake of lycopene can be beneficial to restrict or prevent the I/R injury of skeletal muscle and can thus enhance the healing following limb ischemia due to traumatic or vascular events or extensive surgical procedures with tourniquet use. These findings are in line with the studies which investigated the protective effects of lycopene against I/R injury of various tissues other than skeletal muscle. Ischemia/reperfusion injury is a process involving multiple complex mechanisms and the outcomes of these injuries are quite debilitating or life-threatening. In the literature, there are studies demonstrating both anti-inflammatory and antioxidant activities of lycopene.[38–41] To our knowledge, there is no previous animal study investigating the effects of lycopene on I/R injury of skeletal muscle. The results of the present study show the protective effects of lycopene on muscle tissue exposed to I/R injury and strongly support the claim that lycopene has antioxidative effects. However, antioxidative effects alone can hardly explain the protective effects of lycopene against skeletal muscle injury. Various mechanisms, including anti-inflammatory effects, may contribute to its protective activities.

Conclusion The results of this study demonstrate the antioxidative and cytoprotective effects of lycopene against I/R injury of skeletal muscle. Since lycopene is a safe and potent antioxidative natural substance and is available for oral intake by diet or supplementation, its use before extensive limb surgeries, including tourniquet use as well as in cases with limb ischemia, seems favorable. Antioxidative effects alone can hardly explain the protective effects of lycopene against I/R induced skeletal muscle injury. Further studies may be required to gain deeper insight into the lycopene’s mechanism of action before introducing lycopene into clinical use for restriction or prevention of the I/R injuries. Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Kirişçi et al. The protective effects of lycopene on I/R injury in rat hind limb muscle model

Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: M.K., B.G., H.G.; Design: M.K., B.G., H.G.; Supervision: B.G.; Fundings: M.K.; Materials: M.K., M.S., Ü.K.; Data: M.K., M.S., Ü.K., A.D.; Analysis: M.S., Ü.K., A.D.; Literature search: M.K., B.G.; Writing: M.K., B.G.; Critical revision: M.K., B.G. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

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16. Kılıç Y, Özer A, Tatar T, Zor MH, Kirişçi M, Kartal H, et al. Effect of picroside II on hind limb ischemia reperfusion injury in rats. Drug Des Devel Ther 2017;11:1917−25. 17. Yonar ME. Protective effect of lycopene on oxidative stress and antioxidant status in Cyprinus carpio during cypermethrin exposure. Environ Toxicol 2013;28:609–16. 18. Darwish SF, El-Bakly WM, Arafa HM, El-Demerdash E. Targeting TNF-α and NF-κB activation by bee venom: role in suppressing adjuvant induced arthritis and methotrexate hepatotoxicity in rats. PLoS One 2013;8:e79284. 19. Kim H. Inhibitory mechanism of lycopene on cytokine expression in experimental pancreatitis. Ann N Y Acad Sci 2011;1229:99–102. 20. Rousseau EJ, Davison AJ, Dunn B. Protection by beta-carotene and related compounds against oxygen-mediated cytotoxicity and genotoxicity: implications for carcinogenesis and anticarcinogenesis. Free Radic Biol Med 1992;13:407–33. 21. Rao AV, Agarwal S. Role of lycopene as antioxidant carotenoid in the prevention of chronic diseases: a review. Nutrit Res 1999;19:305−23. 22. Marcotorchino J, Romier B, Gouranton E, Riollet C, Gleize B, Malezet-Desmoulins C, et al. Lycopene attenuates LPS-induced TNF-α secretion in macrophages and inflammatory markers in adipocytes exposed to macrophage-conditioned media. Mol Nutr Food Res 2012;56:725−32. 23. Mellert W, Deckardt K, Gembardt C, Schulte S, Van Ravenzwaay B, Slesinski R. Thirteen-week oral toxicity study of synthetic lycopene products in rats. Food Chem Toxicol 2002;40:1581–8. 24. Michael McClain R, Bausch J. Summary of safety studies conducted with synthetic lycopene. Regul Toxicol Pharmacol 2003;37:274–85. 25. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978;52:302–10. 26. Beyer WF Jr, Fridovich I. Assaying for superoxide dismutase activity: some large consequences of minor changes in conditions. Anal Biochem 1987;161:559–66. 27. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70:158–69. 28. Land WG. The role of postischemic reperfusion injury and other nonantigen-dependent inflammatory pathways in transplantation. Transplantation 2005;79:505–14. 29. Le Moine O, Louis H, Stordeur P, Collet JM, Goldman M, Devière J. Role of reactive oxygen intermediates in interleukin 10 release after cold liver ischemia and reperfusion in mice. Gastroenterology 1997;113:1701–6. 30. Takhtfooladi HA, Takhtfooladi MA. Effect of curcumin on lung injury induced by skeletal muscle ischemia/reperfusion in rats. Ulus Travma Acil Cerrahi Derg 2019;25:7–11. 31. Elmali N, Esenkaya I, Karadağ N, Taş F, Elmali N. Effects of resveratrol on skeletal muscle in ischemia-reperfusion injury. Ulus Travma Acil Cerrahi Derg 2007;13:274–80. 32. Ozyurt H, Ozyurt B, Koca K, Ozgocmen S. Caffeic acid phenethyl ester (CAPE) protects rat skeletal muscle against ischemia-reperfusion-induced oxidative stress. Vascul Pharmacol 2007;47:108–12. 33. Koca K, Yurttaş Y, Yıldız C, Caycı T, Uysal B, Korkmaz A. Effect of hyperbaric oxygen and ozone preconditioning on oxidative/nitrosative stress induced by tourniquet ischemia/reperfusion in rat skeletal muscle. Acta Orthop Traumatol Turc 2010;44:476–83. 34. Kaya C, Karabulut R, Turkyilmaz Z, Sonmez K, Kulduk G, Gülbahar Ö, et al. Lycopene has reduced renal damage histopathologically and biochemically in experimental renal ischemia-reperfusion injury. Ren Fail 2015;37:1390−5. 35. Hua Y, Xu N, Ma T, Liu Y, Xu H, Lu Y. Anti-Inflammatory Effect of Lycopene on Experimental Spinal Cord Ischemia Injury via Cyclooxygenase-2 Suppression. Neuroimmunomodulation 2019;26:84–92.

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pression. Nutr Cancer 2011;63:427−34. 39. Ghavipour M, Saedisomeolia A, Djalali M, Sotoudeh G, Eshraghyan MR, Moghadam AM, et al. Tomato juice consumption reduces systemic inflammation in overweight and obese females. Br J Nutr 2013;109:2031−5. 40. Davies MJ. Singlet oxygen-mediated damage to proteins and its consequences. Biochem Biophys Res Commun 2003;305:761–70. 41. Conn PF, Schalch W, Truscott TG. The singlet oxygen and carotenoid interaction. J Photochem Photobiol B 1991;11:41–7.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Sıçan arka uzuv kas modelinde iskemi/reperfüzyon hasarına yönelik likopenin koruyucu etkisi Dr. Mehmet Kirişçi,1 Dr. Bülent Güneri,2 Dr. Muhammed Seyithanoğlu,3 Dr. Ülkü Kazancı,4 Dr. Adem Doğaner,5 Dr. Hakan Güneş6 Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Kalp Damar Cerrahi Anabilim Dalı, Kahramanmaraş Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Kahramanmaraş Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Tıbbi Biyokimya Anabilim Dalı, Kahramanmaraş 4 Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Tıbbi Patoloji Anabilim Dalı, Kahramanmaraş 5 Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Biyoistatistik ve Tıbbi Bilişim Anabilim Dalı, Kahramanmaraş 6 Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Kardiyoloji Anabilim Dalı, Kahramanmaraş 1 2 3

AMAÇ: Önemli bir mortalite ve morbidite sebebi olan iskelet kasının akut iskemi/reperfüzyon (I/R) hasarı oksidatif stres ile ilişkilidir. Etkin bir antioksidatif ve bir tür karotenoid pigment olan likopen meyve ve sebzelerde bulunmaktadır. Çalışmamız sıçan arka uzuv kas modelinde likopenin İ/R hasarına karşı koruyucu etkisini incelemektedir. GEREÇ VE YÖNTEM: Otuz iki adet Wistar-albino türü sıçan kontrol, likopen, İ/R ve İ/R+likopen gruplarına rasgele dağıtıldı. Likopen ve İ/ R+likopen gruplarındaki sıçanlar deneyden önceki 15 gün boyunca ağızdan günde, 10 mg/kg miktarında likopen aldı. Tüm sıçanlara genel anestezi altında böbrek altı seviyesinde abdominal aorta diseksiyonu uygulandı. I/R ve I/R+likopen gruplarında aorta, böbrek altı seviyesinde iki saat süre ile klemp kullanılarak kapatıldı. Ardından bu gruplarda iki saat süre ile reperfüzyona olanak sağlandı. Feda edildikten sonra sıçanların arka uzuv kasından biyokimyasal ve histopatolojik inceleme için örnekler alındı. BULGULAR: I/R+likopen grubunda serum ve doku malondialdehit ve iskemi modifiye albumin düzeyleri I/R grubuna kıyasla anlamlı derecede düşüktü (p<0.001). I/R grubunda serum glutatyon peroksidaz (GSH-Px) düzeylerinin kontrol ve I/R+likopen gruplarındakine göre anlamlı derecede düşük olduğu belirlendi (p<0.05). I/R grubunda doku GSH-Px düzeyleri likopen grubundakine göre anlamlı derecede düşüktü (p=0.003). Diğer üç gruba oranla I/R grubunda serum süperoksit dismutaz (SOD) düzeylerinin anlamlı derecede düşük olduğu saptandı (p<0.001). I/R grubunda doku SOD seviyeleri kontrol ve likopen gruplarındakine göre anlamlı derecede düşüktü (p=0.005). Histopatolojik incelemelerde I/R+likopen grubunda I/R hasarına bağlı enflamatuvar değişimlerin belirgin olarak az olduğu görüldü. TARTIŞMA: Çalışmamız sıçan iskelet kası modelinde likopenin I/R hasarına karşı hücre koruyucu etkinliğini göstermektedir. Anahtar sözcükler: Antioksidanlar; iskemi; likopen; reperfüzyon hasarı; turnike. Ulus Travma Acil Cerrahi Derg 2020;26(3):351-360

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doi: 10.14744/tjtes.2020.81456

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EXPERIMENTAL STUDY

Immediate versus delayed primary repair of the sciatic nerve in a nerve transaction model in rats Azmi Tufan, M.D.,1 Feyza Karagöz Güzey, M.D.,1 Burak Eren, M.D.,1 Abdurrahim Taş, M.D.,2 Cihan İşler, M.D.,3 Aslı Kahraman Akkalp, M.D.,4 İlker Güleç, M.D.,1 Vildan Ayşe Yayla, M.D.,5 Murat Çabalar, M.D.5 1

Department of Neurosurgery, Health Sciences University, Bağcılar Training and Research Hospital, İstanbul-Turkey

2

Department of Neurosurgery, Health Sciences University, Gazi Yaşargil Training and Research Hospital, Diyarbakır-Turkey

3

Department of Neurosurgery, İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, İstanbul-Turkey

4

Department of Pathology, İzmir Katip Çelebi University Atatürk Training and Research Hospital, İzmir-Turkey

5

Department of Neurology, Health Sciences University, Bakirköy Dr. Sadi Konuk Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: The debate continues concerning surgical timing in a peripheral nerve injury. This study aims to evaluate the result of immediate versus delayed primary (after seven days) repair of peripheral nerve injury. METHODS: In this study, Wistar rats were divided into four groups as follows: The nerve was sharply transected in Group 1, 2 and 4. It was immediately sutured in Group 1 and sutured seven days later in Group 2, and it was not sutured in Group 4. In Group 3, the left sciatic nerve was only explored. Eight weeks later, tissue samples were extracted from the injured nerve area. Both gastrocnemius muscles were weighed. The nerve samples were examined for axon degeneration. Myelin vacuolization, axon irregularity, and edema/ inflammation parameters were evaluated. RESULTS: There were not any significant differences in the score of axon degeneration and the weight of the gastrocnemius muscle between the immediate and delayed primary repair groups. However, these parameters were significantly better in both repair groups than to be in the control group and significantly worse than to be in the sham-operated group. CONCLUSION: To delay the repair about one week did not affect the histological results and weight of the muscle that was innervated by the sectioned nerve comparing to be in the immediate repair in a sciatic nerve transaction model in rats. Keywords: Nerve injury; nerve transaction; peripheral nerve; peripheral nerve injury; timing of the operation.

INTRODUCTION Peripheral nerve injury is a serious public health problem because it frequently occurs in young and productive people, and it may cause serious disabilities. Surgical treatment is mandatory in almost all of the patients with nerve transaction. The most preferred surgical method for the treatment of peripheral nerve transaction with sharp objects is the primary end-to-end suturing of the proximal and distal nerve ends. There are many studies advocating immediate surgery in these

cases in the literature because the best results occur with this timing.[1,2] However, in some of these patients, early neurorrhaphy may not be reasonable because of the contaminated wound, the presence of concomitant vascular injuries, or the worse general condition of the patient due to other systemic injuries. In this condition, repair of the nerve transaction may require to be delayed for a few days or weeks. There are a few clinical and experimental studies comparing the results of immediate versus delayed (>4 weeks) repair of the nerve in literature. However, there is not much information about the results of the subacute repair of the transected peripheral nerves.

Cite this article as: Tufan A, Karagöz Güzey F, Eren B, Taş A, İşler C, Kahraman Akkalp A, et al. Immediate versus delayed primary repair of the sciatic nerve in a nerve transaction model in rats. Ulus Travma Acil Cerrahi Derg 2020;26:361-365. Address for correspondence: Azmi Tufan, M.D. Sağlık Bilimleri Üniversitesi, Bağcılar Eğitim ve Araştırma Hastanesi, Nöroşirurji Kliniği, İstanbul, Turkey Tel: +90 212 - 440 40 00 / 3313 E-mail: tufanazmi@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):361-365 DOI: 10.14744/tjtes.2019.48579 Submitted: 28.06.2019 Accepted: 23.10.2019 Online: 15.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Tufan et al. Immediate versus delayed primary repair of the sciatic nerve in a nerve transaction model in rats

In this study, we aimed to evaluate the effects of immediate versus subacute, or with the term frequently used in literature, delayed primary (after seven days) repair of peripheral nerve injury[3] on histological results of axon degeneration and weights of end-organ muscles in a transaction type sciatic nerve injury model in rats.

MATERIALS AND METHODS This study was approved by the BADABEM (the local ethical committee for experimental studies in our hospital) (24th September 2014/number 10). In this study, 28 female WistarHannover rats weighing 250–300 g were used. All animals were maintained on a 12-h light/dark cycle with an average room temperature of 22°C, 30% humidity and with food/water available ad libitum.

Experimental Groups The subjects were randomly introduced into the four groups as follows: Group 1: Immediate repair group (n=8): Left sciatic nerve was transected and sutured immediately. Group 2: Delayed primary repair group (n=8): Left sciatic nerve was transected and sutured 7 days later. Group 3: Sham-operated group (n=6): Left sciatic nerve was explored, but not transected. Group 4: Control group (n=6): Left sciatic nerve was transected but not sutured.

site was taken out in Groups 1, 2 and 4. In Group 3, the sample was taken from the similar site that the transaction was performed in the other groups. Both left and right gastrocnemius muscles were also taken out (Fig. 1). Muscles were weighed on a sensitive scale.

Histological Evaluation All evaluations were made under a light microscope by the same pathologist. The sciatic nerve samples were fixed in 10% formaldehyde and routinely processed for paraffin embedding. Four µ thick sections were obtained and stained with hematoxylin-eosin for evaluating myelin vacuolization, axon irregularity and inflammation/edema. They were scored as follow: 0: negative, +: mild, ++: moderate, and +++: high. For statistical analysis, the parameters were also scored by assessing the percentage of the degeneration by 10% intervals (ranging from 0%–100%). Neurofilament immunohistochemistry and toluidine histochemistry were also performed to find out the nerve clearly.

Statistical Evaluation Mean values and standard deviations were calculated for numerical data. F test was used to determine the distribution of the numerical data, and Student’s t-tests were used to compare numerical data of the groups. Mann-Whitney U test was used to compare the ordinary data. It was accepted as significant if p<0.01.

(a)

(b)

Operations Operations were performed under general anesthesia using intraperitoneal ketamine and xylazine injection. After standard exploration of the left sciatic nerve, it was transected with scalpel number 15. In Group 1, the nerve ends were sutured with 8/0 monofilament nylon suture material from perineurium. For all neurorrhaphy, four separated sutures were placed. In Groups 2 and 4, the nerve was transected and both ends were sutured to the fascia of the gastrocnemius muscle from their perineurium. In Group 2, rats were anesthetized in the same manner one week later. The gap between the proximal and distal nerve ends was measured as mm after the tagged sutures were removed, and the nerve stumps were sutured to each other with the same manner as in Group 1. In Group 3, the sciatic nerve was explored but not transected. In Group 4, the tag sutures were removed and the gap between the nerve ends was measured before killing the subjects eight weeks after transaction. All animals were killed with intraperitoneal pentothal injection eight weeks later. Both legs were observed and then left sciatic nerve sample 6 mm in length that centered the repair 362

Figure 1. The left (a) and right (b) gastrocnemius muscles of a subject from Group 4.

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Tufan et al. Immediate versus delayed primary repair of the sciatic nerve in a nerve transaction model in rats

RESULTS

2

A subject was lost during the study period in Group 2 and excluded from this study.

Measurements of the Gap The gap between proximal and distal ends of the transected nerve was <4 mm (mean 2.75 mm) in all subjects of Group 2 during neurorrhaphy one week later, however it was >4 mm (mean 7 mm) in all subjects of Group 4 during the collection of the nerve samples eight weeks later (p<0.001) (Table 1).

Weights of the Muscles The weights of the left gastrocnemius muscles were not statistically different in Groups 1 and 2 (p=0.57). However, the left gastrocnemius muscles were significantly lighter in both of the study groups (Groups 1 and 2) than to be in Group 3 (p<0.001), and significantly heavier than to be in the Group 4 (p<0.001 and p=0.0017, respectively). In Groups 1, 2 and 4, the left muscle was lighter than the own right muscle (p<0.001 for Groups 1 and 4 and p=0.007 for Group 2). The weights of the left and right muscles were not statistically sigTable 1. Measurements of the gap between the nerve stumps and histological grades of axonal degeneration of the groups were given Group 1 Group 2 Group 3 Group 4 NA

2–4/2.75

NA

5–8/7

mean mm) Histological grade 20–50/35 20–60/40 0–5/5 50–60/60 (distribution/median) NA: Not applicable.

Table 2. The weights of the right and the left gastrocnemius muscles of the groups were given

Group 1

Group 2

Group 3

Group 4

Right 1.765 1.64 1.56 1.55 Left 0.87 0.95 1.79 0.38 p

1.4 1

Neurorrhapy in Group 1 was easier than to be in Group 2 because there were more adhesions in Group 2. However, neurorrhaphy was accomplished in all subjects of both groups. There was atrophy of the left leg and compression wounds in the left foot of all subjects of Group 4 at the end of the eight weeks.

Gap (distribution/

1.6 1.2

Observations

Right Left

1.8

<0.001 0.007 0.02 <0.001

The weights were given as mg. The significant p values were shown as bold and italic characters.

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0.8 0.6 0.4 0.2 0

Group 1

Group 2

Group 3

Group 4

Figure 2. The graphic showing the mean weights of the right and left gastrocnemius muscles as mg in the groups.

nificant in Group 3 (p=0.02). The mean weights of the muscles were given in Table 2 and shown in Figure 2.

Histological Findings The score of the axon degeneration was significantly lower in Groups 1 and 2 than to be in Group 4 (p<0.01), and significantly higher than to be in Group 3 (p<0.01). There was not a statistically significant difference between Groups 1 and 2 (p=0.68) (Table 1).

DISCUSSION Peripheral nerves have a relatively good regeneration capacity according to the central nervous tissue. However, this capacity is usually inadequate in the complete or nearly complete nerve injuries. In this condition, surgical nerve repair is mandatory and primary end-to-end neurorrhaphy is preferable.[1] The aim of surgery is to get facing each other of the fascicles of the proximal and distal nerve stumps according to their functions. The motor fascicles of the proximal nerve stump must be joined to the motor fascicles of the distal nerve stump, and the sensory ones must be joined to the sensory fascicles. Timing of repair is one of the most important factors affecting the regeneration of the injured nerve and recovery of its motor and sensory functions. If the nerve is cleanly injured by a sharp object, immediate repair is a preferable timing as there is no scarring, with clear fascicles ends, the short gap between the nerve stumps and intraoperative stimulation of the distal nerve can be performed in the early period of the injury.[4] In addition, early rehabilitation can be started if the early repair is done.[5] However, the peripheral nerve injuries are frequently associated with the vascular injuries, the wound may be contaminated, or the general condition of the patient may not be good due to other systemic injuries. Thus, the repair of the nerve may not be performed during a few days after injury. In addition, better operation conditions, such as more favorable suture materials, microsurgical equipment, and the most importantly, a more experienced surgeon, can provide in a few days if the nerve repair does not perform immediately.[6] 363


Tufan et al. Immediate versus delayed primary repair of the sciatic nerve in a nerve transaction model in rats

There are some clinical and experimental studies that compare the results of early and late (usually more than after four weeks) repair.[7–9] Jivan et al.[9] reported that the clinical results were significantly better if the brachial plexus injuries were repaired in shorter than two weeks. Erakat et al.[8] reported that the injury to surgery interval is the most significant prognostic factor in a study evaluating the timing of repair of the lingual nerve injury. Gezercan et al.[3] reported in a series consisting of 25 nerve injuries repaired 3–30 months after the injury that only 23.4% of the cases had 4–5/5 motor strength at the end of a 15 month follow-up period. There are some studies reporting better clinical results with early primary repair than delayed repair for upper extremity nerves.[10–12] Ruijs et al.[13] reported in a meta-analysis of 23 series consisting of 623 median and ulnar nerve injuries that delay in surgery was a negative predictive factor, and its effect gradually increased per month. In recent studies on intracellular signaling pathways initiating rapidly after peripheral nerve injuries, early repair of the nerve has clear advantages.[2] Saito and Dahlin[7] reported in an experimental study that if the repair delays over 30 days, nerve regeneration impairs. It was reported that the decrease in the number of Schwann cells expressing the transcription factors with time after the injury has a negative effect on axonal growth.[2,14,15] Fu and Gordon et al.[16] also reported in an experimental study that the rate of reinnervation of the muscles was significantly higher in the subjects whose nerves were repaired immediately than to be in the subjects whose nerves were repaired six months later. Jonsson et al.[14] reported an experimental study evaluating the effects of delayed peripheral nerve repair on nerve regeneration and target muscle recovery and they did not found any difference for numbers of regenerated axons between the immediate and the one-month repair groups. However, axonal area was statistically smaller in the one-month repair group. There is only one study comparing the results of immediate and delayed primary repair of the complete sectioned nerve in literature. Piskin et al.[17] reported a rabbit study evaluating the results of early versus three days later, primary repair of the sciatic nerve injury. They did not find any histological and stereological difference between two-timing. In this study, we chose the 7th day after the injury as “subacute” or “delayed primary” repair time for two reasons: One of them was that this time span is usually sufficient to make ready the patient for the operation in ideal conditions, and the second was that we want to take advantage of the stimulating capacity of the distal Schwann cells. After the complete section of the nerve, the Schwann cells increased in number and they significantly expressed nerve growth factor (NGF) receptors at the distal portion of the nerve in a few days after nerve injury. Activation of these receptors stimulates the regeneration of axonal sprouts.[1] In a study, it was shown that the level of NGF receptors increased to 50 fold from the 364

baseline level seven days after injury.[18] However, denervated Schwann cells gradually lose their ability to support the growing axons in time if there is no connection between the newly sprouting axons.[19] The results of our study demonstrated that one week delay of the repair did not affect the histological results and weight of the muscle innervated by the nerve. These results were significantly better than to be in the control group without nerve repair, and they were significantly worse than to be in the sham-operated group without the nerve section, as expected. These results were thought that delayed primary repair of the totally sectioned peripheral nerve for one week after the injury did not badly affect the regeneration of the nerve comparing to the immediate repair. Therefore, to delay the repair about one week is a logical choice until providing the optimal conditions in the cases cannot be operated immediately after injury due to various reasons. If the nerve repair is delayed, the gap between the stumps of the nerve gradually increases due to the retraction and scar formation. This condition causes difficulty in primary repair. Moore et al.[4] advocated tagging the nerve ends to the underlying fascia and muscle tissues to avoid the increase of the gap between the cut nerve ends till the repair if it is delayed. Wu et al.[20] used this technique in an experimental model. We also performed this technique in the subjects of control and delayed repair groups immediately after the sciatic nerve section. In the delayed repair group, the gap was less than 4 mm in all subjects at seven days after injury. This distance is shorter than the 20% of the whole sciatic nerve length (about 2 cm) in the rat. Sunderlund and Bradley[21] reported that peripheral nerves could be lengthened about 20% of their whole length without any damage. Therefore, this timing is a good choice for primary repair of the peripheral nerve without stretching. In the control group, the mean gap between proximal and distal stumps of the nerves was 7 mm, and it was >4 mm in all subjects eight weeks after injury despite the presence of the tagged sutures.

Conclusion Delaying the repair for one week as elective surgery did not badly affect the histological results and weight of the muscle that was innervated by the sectioned nerve compared to the immediate repair group in a sciatic nerve transaction model in rats. Therefore, it was thought that the repair of the transected nerves might be delayed about one week if the conditions related to the patients or centers are not optimum. However, it is required some clinical studies if these results are also valid for human patients or not. Ethics Committee Approval: This study was approved by the BADABEM (the local ethical committee for experimental studies in our hospital) (24th September 2014/number 10). Peer-review: Internally peer-reviewed. Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Tufan et al. Immediate versus delayed primary repair of the sciatic nerve in a nerve transaction model in rats

Authorship Contributions: Concept: A.T., F.K.G., V.A.Y.; Design: A.T., F.K.G., B.E., C.İ., V.A.Y., M.Ç.; Supervision: F.K.G., V.A.Y.; Fundings: A.T., A.Taş., C.İ., M.Ç.; Materials: A.T., A.Taş., M.Ç., V.A.Y., B.E., İ.G., A.K.A.; Data: A.T., M.Ç., A.Taş., C.İ.; Analysis: A.T., F.K.G., V.A.Y., M.Ç., C.İ., İ.G., B.E., A.K.A.; Literature search: A.T., F.K.G., A.Taş., M.Ç., V.A.Y., C.İ., İ.G., B.E., A.K.A.; Writing: A.T., F.K.G., B.E., A.Taş., C.İ., A.K.A., İ.G., V.A.Y., M.Ç.; Critical revision: A.T., F.K.G., V.A.Y., İ.G., B.E., A.K.A., C.İ., M.Ç. Conflict of Interest: None declared. Financial Disclosure: This study was supported by Bağcılar Training and Research Hospital.

REFERENCES 1. Campbell WW. Evaluation and management of peripheral nerve injury. Clin Neurophysiol 2008;119:1951–65. 2. Dahlin LB. The role of timing in nerve reconstruction. Int Rev Neurobiol 2013;109:151–64. 3. Gezercan Y, Menekşe G, Ökten Aİ, Arslan A, Özsoy KM, Ateş T, et al. The Outcomes of Late Term Surgical Treatment of Penetrating Peripheral Nerve Injuries. Turk Neurosurg 2016;26:146−52. 4. Moore AM, Wagner IJ, Fox IK. Principles of nerve repair in complex wounds of the upper extremity. Semin Plast Surg 2015;29:40–7. 5. Sinha S, Khani M, Mansoori N, Midha R. Adult brachial plexus injuries: Surgical strategies and approaches. Neurol India 2016;64:289–96. 6. Nouraei MH, Hosseini A, Salek S, Nouraei F, Bina R. Median and ulnar nerve injuries; what causes different repair outcomes?. Adv Biomed Res 2015;4:215. 7. Saito H, Dahlin LB. Expression of ATF3 and axonal outgrowth are impaired after delayed nerve repair. BMC Neurosci. 2008;9:88. 8. Erakat MS, Chuang SK, Shanti RM, Ziccardi VB. Interval between injury and lingual nerve repair as a prognostic factor for success using type I collagen conduit. J Oral Maxillofac Surg 2013;71:833–8. 9. Jivan S, Kumar N, Wiberg M, Kay S. The influence of pre-surgical delay

on functional outcome after reconstruction of brachial plexus injuries. J Plast Reconstr Aesthet Surg 2009;62:472–9. 10. Birch R, Raji AR. Repair of median and ulnar nerves. Primary suture is best. J Bone Joint Surg Br 1991;73:154–7. 11. Leclercq DC, Carlier AJ, Khuc T, Depierreux L, Lejeune GN. Improvement in the results in sixty-four ulnar nerve sections associated with arterial repair. J Hand Surg Am 1985;10:997–9. 12. Merle M, Amend P, Foucher G, Michon J. Plea for the primary microsurgical repair of peripheral nerve lesions. A comparative study of 150 injuries of the median or the ulnar nerve with a follow-up of more than 2 years. [Article in French] Chirurgie 1984;110:761–71. 13. Ruijs AC, Jaquet JB, Kalmijn S, Giele H, Hovius SE. Median and ulnar nerve injuries: a meta-analysis of predictors of motor and sensory recovery after modern microsurgical nerve repair. Plast Reconstr Surg 2005;116:484–96. 14. Jonsson S, Wiberg R, McGrath AM, Novikov LN, Wiberg M, Novikova LN, et al. Effect of delayed peripheral nerve repair on nerve regeneration, Schwann cell function and target muscle recovery. PLoS One 2013;8:e56484. 15. Kuffler DP. An assessment of current techniques for inducing axon regeneration and neurological recovery following peripheral nerve trauma. Prog Neurobiol 2014;116:1–12. 16. Fu SY, Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation. J Neurosci 1995;15:3886–95. 17. Piskin A, Altunkaynak BZ, Çitlak A, Sezgin H, Yazıcı O, Kaplan S. Immediate versus delayed primary nerve repair in the rabbit sciatic nerve. Neural Regen Res 2013;8:3410–5. 18. Taniuchi M, Clark HB, Johnson EM Jr. Induction of nerve growth factor receptor in Schwann cells after axotomy. Proc Natl Acad Sci U S A 1986;83:4094–8. 19. Sulaiman OA, Gordon T. Effects of short- and long-term Schwann cell denervation on peripheral nerve regeneration, myelination, and size. Glia 2000;32:234–46. 20. Wu P, Spinner RJ, Gu Y, Yaszemski MJ, Windebank AJ, Wang H. Delayed repair of the peripheral nerve: a novel model in the rat sciatic nerve. J Neurosci Methods 2013;214:37–44. 21. Sunderlund S, Bradley KC. Stress–strain phenomena in human peripheral nerve trunks. Brain 1961;84:102−9.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Sıçanlarda sinir transeksiyon modelinde siyatik sinirin acil ve gecikmeli primer onarımı Dr. Azmi Tufan,1 Dr. Feyza Karagöz Güzey,1 Dr. Burak Eren,1 Dr. Abdurrahim Taş,2 Dr. Cihan İşler,3 Dr. Aslı Kahraman Akkalp,4 Dr. İlker Güleç,1 Dr. Vildan Ayşe Yayla,5 Dr. Murat Çabalar5 Sağlık Bilimleri Üniversitesi, Bağcılar Eğitim ve Araştırma Hastanesi, Nöroşirürji Kliniği, İstanbul Sağlık Bilimleri Üniversitesi, Gazi Yaşargil Eğitim ve Araştırma Hastanesi, Nöroşirürji Kliniği, Diyarbakır İstanbul Üniversitesi-Cerrahpaşa, Cerrahpaşa Tıp Fakültesi, Nöroşirürji Anabilim Dalı, İstanbul 4 İzmir Katip Çelebi Üniversitesi, Atatürk Eğitim ve Araştırma Hastanesi, Patoloji Kliniği, İzmir 5 Sağlık Bilimleri Üniversitesi, Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Nöroloji Kliniği, İstanbul 1 2 3

AMAÇ: Periferik sinir yaralanmasında cerrahinin zamanlaması hala tartışmalıdır. Periferik sinir hasarının derhal ve gecikmiş primer (yedi gün sonra) onarımının sonuçları değerlendirildi. GEREÇ VE YÖNTEM: Wistar cinsi sıçanlar 4 gruba ayrıldı: Sinir keskin şekilde Grup 1, 2 ve 4’te kesildi. Grup 1’de hemen dikildi ve Grup 2’de yedi gün sonra dikildi ve Grup 4’te dikilmedi. Grup 3’te sol siyatik sinir sadece eksplore edildi. Sekiz hafta sonra, yaralanan sinir bölgesinden doku örnekleri alındı. Her iki gastrocnemius kasları tartıldı. Sinir örnekleri akson dejenerasyonu açısından incelendi. Miyelin vakuolizasyonu, akson düzensizliği ve ödem/enflamasyon parametreleri değerlendirildi. BULGULAR: Acil ve gecikmiş primer onarım grupları arasında akson dejenerasyonu skoru ve gastrocnemius kasının ağırlığı açısından anlamlı fark yoktu. Bununla birlikte, bu parametreler her iki tamir grubunda da kontrol grubundan anlamlı derecede daha iyiydi ve sinir kesisi yapılmayan gruptan anlamlı derecede daha kötüydü. TARTIŞMA: Sıçanlarda siyatik sinir transeksiyon modelinde onarımın yaklaşık bir hafta geç yapılması acil onarım ile karşılaştırıldığında, kesilmiş sinirin uyardığı kasın histolojik sonuçlarını ve ağırlığını etkilememiştir. Anahtar sözcükler: Operasyon zamanlaması; periferik sinir; periferik sinir hasarı; sinir hasarı; iinir transeksiyonu. Ulus Travma Acil Cerrahi Derg 2020;26(3):361-365

doi: 10.14744/tjtes.2019.48579

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EXPERIMENTAL STUDY

The protective effects of adalimumab on intestinal injury induced with infrarenal aortic occlusion Ahmet Pergel, M.D.,1 Levent Tumkaya, M.D.,2 Gökhan Demiral, M.D.,1 Muhammet Kadri Çolakoğlu, M.D.,1 Süleyman Kalcan, M.D.,1 Ali Özdemir, M.D.,1 Tolga Mercantepe, M.D.,2 Başar Erdivanlı, M.D.,3 Adnan Yılmaz, M.D.4 1

Department of General Surgery, Recep Tayyip Erdoğan University Faculty of Medicine, Rize-Turkey

2

Department of Histology and Embryology, Recep Tayyip Erdoğan University Faculty of Medicine, Rize-Turkey

3

Department of Anesthesia and Reanimation, Recep Tayyip Erdoğan University Faculty of Medicine, Rize-Turkey

4

Department of Biochemistry, Faculty of Medicine, Recep Tayyip Erdoğan University Faculty of Medicine, Rize-Turkey

ABSTRACT BACKGROUND: The present study aims to observe the effects of ischemia-reperfusion (IR) on small intestines at a molecular level and to prospectively assess the potential preventive role of adalimumab (ADA) and antioxidants. METHODS: A total of 24 male Sprague–Dawley rats were randomly divided into three groups–a control group, an IR group and an IR+ADA group. RESULTS: Although there was no change in SOD levels in the small bowel tissue of the IR group, we observed increased malondialdehyde (MDA) levels and increased numerical density of caspase-3 and TNF-α positive enterocytes p=0.00 and p=0.00, respectively). We also observed that IR caused the degeneration of villus crypt structures. CONCLUSION: We found that ADA treatment reduced MDA levels and decreased the numerical density of caspase-3 and TNF-α positive enterocytes compared to the IR group (p=0.00; p=0.011; p=0.00, respectively). We conclude that ADA can be beneficial in preventing intestinal injury that arises from IR. Keywords: Adalimumab; intestinal injury; ischemia; oxidative stress; rat; reperfusion.

INTRODUCTION Intestinal ischemia-reperfusion (IR) injury, seen after various surgical and clinical situations, such as thoracoabdominal aortic surgery, liver transplantation, intestinal transplantation, strangulated hernias, acute mesenteric ischemia, shock, trauma, and neonatal necrotizing enterocolitis, is an important clinical problem that causes approximately 50–80% of all deaths in surgical intensive care units after major traumas.[1,2] The small intestine is one of the most ischemia-sensitive organs.[3,4] Occlusion of the infrarenal abdominal aorta may also cause ischemic injury, and cell and tissue damage may also occur in remote organs due to complex mechanisms involv-

ing, for example, reactive oxygen species (ROS), neutrophil infiltration, and the release of inflammatory mediators when reperfusion is achieved.[5,6] ROS cause cellular damage by negatively affecting antioxidant defense mechanisms by reducing Superoxide dismutase (SOD) levels and increasing malondialdehyde (MDA) levels.[7] The most important mediator that initiates the inflammatory process in IR injury is thought to be tumor necrosis factor-alpha (TNF-α).[8] The effects of TNF on IR injury have not been fully explained, but it has been shown that TNF is the most important factor in apoptosis. [8,9] In addition, recent studies have shown that ROS cause DNA damage and lead to caspase-dependent apoptosis.[10,11] In recent studies, intestinal IR has been reported to increase

Cite this article as: Pergel A, Tumkaya L, Demiral G, Çolakoğlu MK, Kalcan S, Özdemir A, et al. The protective effects of adalimumab on intestinal injury induced with infrarenal aortic occlusion. Ulus Travma Acil Cerrahi Derg 2020;26:366-372. Address for correspondence: Ahmet Pergel, M.D. Recep Tayyip Erdoğan Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, 53010 Rize, Turkey Tel: +90 464 - 213 04 91 E-mail: tolgamercantepe@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(3):366-372 DOI: 10.14744/tjtes.2019.59607 Submitted: 26.03.2019 Accepted: 24.06.2019 Online: 15.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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caspase-3 activation, an irreversible terminal event in the activation of apoptosis. However, some studies have reported that TNF-α blockers suppress inflammation that arises from TNF-α and eliminate free oxygen radicals (scavengers).[12,13] Other studies have found that anti-TNF-a, when given prophylactically has a protective, effect that reduces IR injury. [14,15] After the TNF inhibitors infliximab and etanercept, adalimumab (ADA)—approved by the Food and Drug Administration for clinical use in treating rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, moderate to severe chronic psoriasis, and juvenile idiopathic arthritis—is the first anti-TNF-α monoclonal antibody obtained from humans.[16,17] In light of this information, we studied the effects of infrarenal aortic IR on the small intestine at the molecular level. Following, we discuss the possible prophylactic potential of ADA and antioxidants

MATERIALS AND METHODS Animals Twenty-four Sprague-Dawley male rats (250±50g and 3–5 months old) were used in the present study. All animals were fed and maintained at 55–60% humidity and 22±2 °C room temperature in laboratory animal unit, which is lightened for 12 hours and darkened for 12 hours at University’s Faculty of Medicine Basic Medical Sciences Experimental Animals Application Unit. All animals received humane care according to the criteria outlined in the ‘Guide for the Care and Use of Laboratory Animals’ prepared by the National Academy of Sciences and published by the National Institutes of Health. This study was approved by the University Animal Ethical Committee (ID: 2015/19).

Experimental Groups A total of 24 male Sprague-Dawley rats were randomly divided into three groups. Control group (n=8), IR (n=8) and IR+ADA (n=8). ADA (Humira; Abbott, Abbott Park III, 40 mg/0.8 mL) was intraperitoneally administered as 50mg/kg (single dose) after being diluted with saline five days before I/R.

The Technique of Intestinal I/R Before ischemia-reperfusion, animals were given only water for the last 12 hours. For anesthesia, 50 mg/kg intraperitoneal (i.p.) Ketamine hydrochloride (Ketalar®, Parke-Davis), and 10 mg/kg i.p. xylazine HCl (Alfaz®, Alfasan International B.V., Woerden, The Netherlands) were administered. The rats were placed in the supine position under a heating lamp. The abdominal skin was shaved, washed with an antiseptic solution, and a midline cross-section was performed. The intestines were carefully pulled to the left to reveal the abdominal aorta. The atraumatic microvascular clamp was placed in the abdominal aorta under the level of the renal artery. After making sure that there was no pulsation in the distal aorta, Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

the skin was closed to prevent heat and fluid loss. The skin area was approximated with a suture following the administration of warm saline to peritoneal cavity to prevent loss of abdominal fluid after the clamp procedure. To perform arterial pressure monitoring, the right carotid artery was connected to the monitor with a transducer set and the invasive pressure monitoring was continued during the experiment. One hour after the ischemia, the clamp was opened and the pulse was controlled at distal aorta and reperfusion was allowed for 1 hour.[18–20] An only midline laparotomy was performed on the animals in the control group. Blood samples were taken with Median sternotomy for biochemical analysis from the right ventricle of all animals. For histopathological examination, ileal segments were excised and stored under appropriate conditions.

Biochemical Investigations Preparation of Homogenates The small intestine tissue samples were cold phosphate buffer was added 2 times the volume tissue weight and homogenized for 30 min. Homogenized intestinal tissues samples were centrifuged at 3000 g for 15 minutes.

SOD Analysis The activity of SOD was measured using colorimetric assay kit (Cayman Chemical Company, Michigan, USA). The procedure for the assay method was according to the instructions provided by the manufacturer. Absorbance was measured at a wavelength of 450 ηm using plate reader. The activity of SOD is presented as U/ml. The intra-assay and inter-assay coefficient of variation were 3.2% and 3.7%, respectively. The dynamic range for the SOD assay kit was 0.025–0.25 U/ml.

The MDA Analysis MDA levels were measured by the double heating method of Draper and Hadley.* The principle of the method is the spectrophotometric measurement of the color generated by the reaction of thiobarbituric acid (TBA) with MDA. The MDA levels are presented as micromol/L.[21]

Histopathological Analysis Procedure The small intestine tissue removed from the rats in all groups was washed with phosphate buffer (pH: 7.4; Sigma-Aldrich, Germany) and then fixed in 10% phosphate-buffered formalin for 36 hours. After fixation, the specimens of the small bowel tissue were implanted in paraffin (Merck Darmstadt, Germany) blocks after routine histological follow-up. Samples of the small intestine were sectioned with a microtome device (Leica RM2525, Lecia, Germany) with a thickness of 3–4 μm. Sections were stained with Harris hematoxylin and Eosin G (H & E; Merck, Darmstadt, Germany). Sections under a light microscope (Olympus BX51, Olympus Corp. Japan) were analyzed. The findings observed in the photos were taken with the digital camera (Olympus DP20, Olympus Corp. Japan). 367


Pergel et al. The protective effects of ADA on intestinal injury induced with infrarenal aortic occlusion

Immunohistochemistry (IHC) Analysis Procedure Following steps were performed for Caspase 3 and TNF-α staining: the sections were deparaffinized and treated with proteinase K solution (20 μg/mL in PBS), washed in distilled water and immersed in 3% hydrogen peroxide. After several washes with PBS, the sections were immersed in an equilibration buffer. Sections were incubated with primary antibody (Caspase 3,1:200, Abcam Rabbit polyclonal to active Caspase-3, UK) and TNF-α (Caspase 3,1:200, Abcam Rabbit polyclonal to active Rabbit polyclonal to TNF-α, UK). After several washes, all sections were incubated in anti-digoxigenin-peroxidase then incubated with 0.06% 3,3-diaminobenzidine tetrahydrochloride (DAB, Sigma Chemical, St. Louis, MO) in PBS. Eventually, sections were counter-stained with Harris hematoxylin (Merck, Darmstadt, Germany).[22]

The Semi-quantitative Analysis In this study, intestinal damage grade scores Chiu et al.[23] methods were calculated using the Olympus DP2-BSW (Ver.2.1 to Ver.2.2, Build 6212, Tokyo, Japan) software system was used. H&E stained sections were put on the microscope tray, and their sectional boundaries were determined using this program. After determining the area, frames separated from each other were determined by histopathologist random (Table 1).

Stereological Analysis The mean IHC positive cell numerical density was calculated using the fractional method, of the Stereo Investigator (MicroBrightField 9.0, Colchester, VT, CA, USA) software system was used. IHC stained (Caspase-3 and TNF-α) sections were put on the microscope tray, and their sectional boundaries were determined using this program. After determining the area, frames separated from each other were determined Table 1. Grading score of the mucosal damage (Chiu et al.) Grade

The sequence of morphological changes

0

Normal mucosal villi.

1

Development of subepithelial Gruenhagen’s space,

usually at the apex of the villus; often with capillary

congestion. 2

Extension of the subepithelial space with moderate

lifting of epithelial layer from the lamina propria.

3

Massive epithelial lifting down the sides of villi.

A few tips may be denuded.

4

Denuded villi with lamina propria and dilated

capillaries exposed. Increased cellularity of the lamina

propria may be noted.

5

Digestion and disintegration of lamina propria;

hemorrhage and ulceration.

368

by systematic random sampling of the sections, according to the rules of space fragmentation with the step interval of the x and y-axis. Then, in 40 different selected areas, of all groups were measured following the method described by Mercantepe.[24]

Statistical Analysis Statistical analysis of the SOD and MDA of all groups was performed using SPSS (IBM SPSS Statistics 18.0, IBM Corporation, Somers, NY, USA). Differences between the groups were tested using one-way analysis of variance (ANOVA) followed by a Tukey HSD test; the numerical data of groups were analyzed (P-value <0.05 was selected as significant). The values were determined as means±standard deviation.

RESULTS Biochemical Results The effects of adalimumab on intestinal SOD and the MDA levels are shown in Table 3. There were statistically non-significant (p>0.05) decreases in the SOD level in the group treated with I/R as compared with the control and I/R+Ada groups. I/R significantly increased the MDA level when compared with the control group (p<0.05). Adalimumab administration significantly decreased the MDA level when compared with the I/R group (p<0.05). There were statistically nonsignificant (p<0.05) in the MDA level in the group treated Table 2. Biochemical analysis results Groups

MDA level (micromol/L)

SOD level (U/ml)

(Mean±SD) (Mean±SD)

Control (n=8)

3.65±0.54

I/R (n=8)

5.07±0.66a 29.09±4.64

30.22±5.27

I/R+ADA (n=8)

3.89±0.50b 28.06±3.40

P=0.00 versus control group; bP=0.00 versus I/R group. SD: Standard deviation; IR: Ischemia-reperfusion; ADA: Adalimumab; MDA: Malondialdehyde; SOD: Superoxide dismutase.

a

Table 3. The mucosal changes following a period of the ischemia/reperfusion are graded Group

Damage grade score

(Median±SD) Control (n=8)

0.00±0.13

I/R (n=8)

5.00±0.00b

I/+ADA Group-treated group (n=8)

2.00±00.35b,c

P<0.05 versus to Control group. cP<0.05 versus to Ischemia/ Reperfusion group. Based on the Kruskal-Wallis test. SD: Standard deviation; IR: Ischemiareperfusion; ADA: Adalimumab.

b

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Table 4. Caspase-3 positive numerical density measurement (mm3) data Group

Caspase-3 positive nume rical density

Control (n=8)

TNF-α positive numerical density

(Mean±SD) (Mean±SD) 4.00±2.27

6.75±3.85

I/R (n=8)

39.00±13.06 64.87±18.33a

I/R+ADA Group-treated group (n=8)

17.63±6.48b 14.50±7.3c

a

a P=0.00 versus to Control group; bP=0.011 versus to I/R group; cP=0.00 versus to I/R group. Tukey HSD test. SD: Standard deviation; IR: Ischemia-reperfusion; ADA: Adalimumab; TNF-a: Tumor necrosis factor alpha.

with adalimumab as compared with the control. In brief, the group treated with Adalimumab, the SOD activity statistically nonsignificant increased than I/R group, and the MDA level activity decreased than I/R group (Table 2).

Light Microscopy Results Light microscopic sections obtained from the intestinal tissue of the control group showed normal histological structural

features. The level of damage for samples taken from the control group was evaluated as 0 (normal mucosa, according to Chiu et al.) (Figs. 1a; Table 4). The intestinal tissue of the ischemia group was widely loss in epithelial cells and ulceration. In addition, ischemia group samples showed the disintegration of the lamina propria with hemorrhage and Crypts of Lieberkuhn degeneration. The degree of structural damage in the ischemia group intestinal tissue samples is five (disintegration of lamina propria, hemorrhage, and ulceration)

(a)

(b)

(c)

(d)

Figure 1. Histology of the small intestine in ischemia damage. H&E. (a) Control group: damage grade score 0; Healthy morphological and intact structures of the mucous membrane (arrow). Crypts of Lieberkuhn (Lb). Lamina propria (Lp). Tunica muscularis (Tm). (x20). (b) Ischemia Group: damage grade score 5; Ischemia group samples showed the disintegration of the lamina propria (spiral arrow), hemorrhage (asterisk) and ulceration (arrow). Crypts of Lieberkuhn degeneration (tailed arrow). (x20). (c) Ischemia+Ada Group: damage grade score 1; Intact structures of the mucous membrane (arrow). Crypts of Lieberkuhn (Lb). Lamina propria (Lp). (x20). (d) Ischemia+Ada Group; Mucous membrane (arrow). Development of subepithelial (Gruenhagen) spaces near the tips of the villi. (x40).

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(Figs. 1b; Table 4). In the ischemia/reperfusion + adalimumab group-treated group, intact structures of the mucous membrane were regularly. However, the development extension of the subepithelial space with moderate epithelial lifting from the lamina propria. The degree of structural damage in the I/R+ADA Group-treated group’s small intestine varies between 2 (2, an extension of the subepithelial space with moderate epithelial lifting from the lamina propria) (Figs. 1c, d) (Table 3).

Immunohistochemical (IHC) Results We found that the I/R administration significantly increased the numerical density of caspase-3 and TNF-α positive intestinal epithelial cells compared to the control group (p=0.00, p=0.00; respectively). However, we found that the numerical density of Caspase-3 and TNF-α positive intestinal epithelial cells in the ADA treatment group was significantly lower than that of the I/R group (p=0.011, p=0.00; respectively) (Table 4; Figs. 2, 3).

The Semi-quantitative Analysis The results also revealed a high level of damage score for sample measurement of the ischemia/reperfusion group (Score: 5) compared to the control group (score: 0) (p=0.00). The I/R+ ADA Group-treated group showed a decreased level of damage score (Score: 2) for sample measurement than the ischemia/reperfusion group (Score: 5) (p=0.00) (Table 3; Fig. 1).

(a)

(b)

DISCUSSION There are many studies on the arteries that directly feed the small intestines, particularly the mesenteric arteries, and IR studies have shown that IR results in a weakened intestinal villus structure, leukocyte infiltration, and hemorrhage of the subepithelial connective tissue. In addition, various studies investigating the indirect effects of IR on the small intestine using abdominal aortic clamping have found that IR is the result of the loss of villus epithelia.[25,26] In the present study, we observed intestinal ulceration due to intestinal epithelial loss. We also observed hemorrhage and the degeneration of intestinal crypts in subepithelial connective tissue. The research has not fully explained the mechanism involved in IR damage to tissue; however, IR has been reported to increase the amount of ROS, resulting in lipid peroxidation. [18,19] Ohkawa et al.[27] reported that MDA levels in intestinal tissues are an index of lipid peroxidation. Cuzzocrea et al.[28] found that IR increased intestinal MDA levels. Zhan et al.[29] found that IR decreased superoxide dismutase (SOD) levels. Although we observed that IR increased SOD levels in our study, we did not observe a statistically significant difference. In this context, we found that infrarenal IR increased the level of intestinal oxidants but did not observe any effects of IR on the antioxidant enzyme SOD. Various studies have reported that abdominal and intestinal IR induces apoptosis in intestinal cells in addition to in-

(c)

Figure 2. Immunohistochemical staining with the immunoperoxidase method and histopathologic examination of the small intestine under the light microscope. (a) Control group. x40. (b) Ischemia group. x20. (c) Ischemia+Ada treated group, immunoperoxidase staining with the anti-caspase-3 antibody. x20.

(a)

(b)

(c)

Figure 3. TNF-α Immunohistochemical staining with the immunoperoxidase method and histopathologic examination of the small intestine under the light microscope. (a) Control group. x40. (a) Ischemia group. x40. (c) Ischemia+Ada treated group.

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creasing ROS. Sun et al.[30] found that intestinal IR induces multiple organ failure, causing apoptosis and oxidative stress. The activation of caspase-3 is considered to be both an irreversible terminal stage of apoptosis and a marker of apoptosis. Gordeeva et al.[31] reported that IR increased caspase-3 levels in their study. In our study, we found that IR caused the apoptosis of enterocytes. The pro-inflammatory cytokine TNF-α has been found to induce oxidative stress in recent studies.[32,33] Neirynck et al.[32] reported that it increased the production of free oxygen radicals. Another study investigated the suppressive effects of TNF-α inhibitors on the pro-inflammatory and pro-oxidative effects of TNF-α and on IR.[18] The present study demonstrated that adalimumab inhibited IR-induced inflammation by decreasing TNF-alpha expression. In addition, Cure et al.[20] employed the abdominal aorta clamping method in investigating why ADA decreased oxidative stress in their study of IR. Kurt et al. employed the infrarenal abdominal aorta clamping method in their study of IR and found that ADA lowered MDA levels.[19] Shen et al.[34] found that ADA reduced apoptosis in their study. Ossendorff et al.[35] reported that ADA reduced caspase-3 expression. Similarly, we found that ADA reduced the IR-induced apoptosis of enterocytes. There are some limitations to our study. Regarding oxidative stress, it should be evaluated in conjunction with other oxidants and antioxidant enzymes and molecules in relation. In addition, the level of intracellular calcium and free oxygen radicals must be assessed vis-à-vis apoptosis. The results of this study indicate that oxidative stress is caused by lipid peroxidation induced by infrarenal abdominal IR. We observed ulceration due to the apoptosis of enterocytes and enterocyte loss in villi. However, we did not observe any effects on SOD, an IR antioxidant enzyme. We found that ADA reduces lipid peroxidation and apoptosis, thus reducing IR damage to the small intestine. This study could be useful in future research on the involvement of antioxidant enzymes other than ROS in IR injury and to better understand other molecular effects associated with the damage that arises from IR. Ethics Committee Approval: This study was approved by the University Animal Ethical Committee (ID: 2015/19). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.P., L.T.; Design: A.P., L.T.; Supervision: S.K., A.Ö.; Fundings: A.P.; Materials: A.P., L.T.; Data: G.D., M.K.C.; Analysis: A.P., B.E., A.Y.; Literature search: T.M., G.D.; Writing: A.P., T.M.; Critical revision: G.D., M.K.C. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

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AP. Effects of n-acetylcysteine in a rat model of ischemia and reperfusion injury. Cardiovasc Res 2000;47:537−48. 29. Zhan L, Zhang Y, Su W, Zhang Q, Chen R, Zhao B, et al. The Roles of Autophagy in Acute Lung Injury Induced by Myocardial Ischemia Reperfusion in Diabetic Rats. J Diabetes Res 2018;2018:5047526. 30. Sun Y, Lian M, Lin Y, Xu B, Li Y, Wen J, et al. Role of p-MKK7 in myricetin-induced protection against intestinal ischemia/reperfusion injury. Pharmacol Res 2018;129:432−42. 31. Gordeeva AE, Sharapov MG, Tikhonova IV, Chemeris NK, Fesenko EE, Novoselov VI, et al. Vascular Pathology of Ischemia/Reperfusion Injury of Rat Small Intestine. Cells Tissues Organs 2017;203:353−64. 32. Neirynck N, Glorieux G, Schepers E, Dhondt A, Verbeke F, Vanholder R. Pro-inflammatory cytokines and leukocyte oxidative burst in chronic kidney disease: culprits or innocent bystanders?. Nephrol Dial Transplant 2015;30:943–51. 33. Shaki F, Ashari S, Ahangar N. Melatonin can attenuate ciprofloxacin induced nephrotoxicity: Involvement of nitric oxide and TNF-α. Biomed Pharmacother 2016;84:1172–8. 34. Shen C, Assche GV, Colpaert S, Maerten P, Geboes K, Rutgeerts P, et al. Adalimumab induces apoptosis of human monocytes: a comparative study with infliximab and etanercept. Aliment Pharmacol Ther 2005;21:251−8. 35. Ossendorff R, Grad S, Stoddart MJ, Alini M, Schmal H, Südkamp N, et al. Autologous Chondrocyte Implantation in Osteoarthritic Surroundings: TNFα and Its Inhibition by Adalimumab in a Knee-Specific Bioreactor. Am J Sports Med 2018;46:431−40.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

İnfrarenal aort oklüzyonu ile oluşan intestinal hasarında adalimumab’ın koruyucu etkisi Dr. Ahmet Pergel,1 Dr. Levent Tumkaya,2 Dr. Gökhan Demiral,1 Dr. Muhammet Kadri Çolakoğlu,1 Dr. Süleyman Kalcan,1 Dr. Ali Özdemir,1 Dr. Tolga Mercantepe,2 Dr. Başar Erdivanlı,3 Dr. Adnan Yılmaz4 Recep Tayyip Erdoğan Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Rize Recep Tayyip Erdoğan Üniversitesi Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, Rize Recep Tayyip Erdoğan Üniversitesi Tıp Fakültesi, Anestezi ve Reaminasyon Anabilim Dalı, Rize 4 Recep Tayyip Erdoğan Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Rize 1 2 3

AMAÇ: Çeşitli cerrahi ve organ transpalantasyonu, strangüle herniasyonlar ve neonatal nekrotizan enterokolit gibi klinik durumlarda ortaya çıkan intestinal iskemi reperfüzyon (I/R) hasarı cerrahi yoğun bakım ünitelerindeki ölümlerin en başlıca sebebini oluşturur. İskemi-reperfüzyon (IR) neden olduğu bağırsak hasarında oksidatif stresin rol oynadığı bildirilmesine rağmen kalıcı bir çözüm bulunamamıştır. Bu çalışmada I/R neden olduğu ince bağırsak üzerindeki etkilerini moleküler düzeyde inceyerek, adalimumab (ADA) ve antioksidanların olası koruyucu potansiyelini geleceğe dönük ele aldık. GEREÇ VE YÖNTEM: Toplam 24 erkek Sprague-Dawley sıçanlar rasgele olarak kontrol, iskemi/reperfüsion (I/R) ve I/R+ADA uygulama grubu olmak üzere üç gruba ayrıldı. BULGULAR: I/R grubunda ince bağırsak dokusunda GSH seviyesinde bir değişiklik gözlemlenmemekle beraber MDA seviyesini ve kaspaz-3 pozitif enterositlerin sayısal yoğunluğunu artırdığını gözledik (sırasıyla, p=0.00; p=0.00). Bunun yanında villus kripta yapılarında dejenerasyona neden olduğunu saptatık. ADA tedavisinin I/R grubuna kıyasla MDA seviyesini ve kaspaz-3 pozitif enterositlerin sayısal yoğunluğunu azalttığını gözlemledik (sırasıyla, p=0.00; p=0.011). TARTIŞMA: Adalimumab, I/R neden olduğu intestinal hasarın önlenmesinde yararlı olabilir. Anahtar sözcükler: Adalimumab; iskemi; intestinal hasar; oksidatif stress; reperfüzyon; sıçan. Ulus Travma Acil Cerrahi Derg 2020;26(3):366-372

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doi: 10.14744/tjtes.2019.59607

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EXPERIMENTAL STUDY

The healing effects of Hyperium perforatum (St. John’s Wort) on experimental alkaline corrosive eosephageal and stomach burns Erkan Güvenç, M.D.,1 Fatih Karabey, M.D.,5

Selahattin Kıyan, M.D.,2 Yiğit Uyanıkgil, M.D.,3 Türker Çavuşoğlu, M.D.,3 Burak Gökçe, M.D.6

Emel Öykü Çetin, M.D.,4

1

Department of Emergency Medicine, Buca Seyfi Demirsoy State Hospital, İzmir-Turkey

2

Department of Emergency Medicine, Ege University Faculty of Medicine Hospital, İzmir-Turkey

3

Department of Histology and Embryology, Ege University Faculty of Medicine, İzmir-Turkey

4

Department of Pharmaceutical Technology, Ege University Faculty of Pharmacy, İzmir-Turkey

5

Department of Biotechnology, Ege University Graduate School of Natural and Applied Sciences, İzmir-Turkey

6

Department of Zoology, Ege University Faculty of Science, İzmir-Turkey

ABSTRACT BACKGROUND: The most frequent etiologic cause is alkaline substances. We investigated the protective effects of the plant St. John ‘s Wort (Hypericum perforatum). METHODS: We included 42 Wistar albino rats weighing between 200–300 grams and divided into six groups as Group 1: Control, Group 2: Burn+Saline (BS), Group 3: Burn+St. John’s Wort (BSJW), Group 4: Burn+Plasebo (BP), Group 5: St. John’s Wort (SJW), Group 6: Placebo (P). After 15 days of treatment, esophagus, stomach and liver tissue samples were derived by dissection for histopathologic and biochemical markers. The cytotoxic effects of formulation on fibroblasts is evaluated in vitro on human dermoblast fibroblast line (HDFa, Gibco Invitrogen cell culture, C-013-5C). RESULTS: The weight of the rats increased in Group 1, 3, 4, 6, decreased in Group 2 and did not change in Group 5. In the BSJW group, submucosal collagen accumulation, muscularis mucosa damage, tunica muscularis damage and collagen accumulation in esophagus were similar to the control group but lesser than BS and placebo group. In the stomach, mucosal damage, gastric gland dilatation, submucosal polymorphonuclear infiltration were similar to the control group and lesser than the BS group. The lethal concentration of SJW was 2.58 gr/mL. CONCLUSION: SJW substrate is effective in protecting the esophagus and stomach in mild to moderate alcali corrosive burns in the subacute period. We should keep in mind the protective effects of STW substrate in alkaline corrosive burns of the gastrointestinal system. Keywords: Alkaline; burn; corrosive; Hypericum Perforatum; Saint John ‘s Wort.

INTRODUCTION The corrosive burns in the gastrointestinal system arise from intentional or accidental oral ingestion of acidic or alkaline substances. They are frequently caused because of unsuitable packages. The printed and visual education programs about

the prevention from the corrosive substances and ideal storage conditions and the limitations to the uncontrolled sale of some corrosive substances decrease the esophageal corrosive burns by %75.[1,2] The alkaline damages are frequently deep burns and cause liquefaction necrosis; the acidic damages are frequently superficial burns and cause coagualation

Cite this article as: Güvenç E, Kıyan S, Uyanıkgil Y, Çetin EÖ, Karabey F, Çavuşoğlu T, et al. The healing effects of Hyperium Perforatum (St. John’s Wort-Kantaron) on experimental alkaline corrosive eosephageal and stomach burns. Ulus Travma Acil Cerrahi Derg 2020;26:373-383. Address for correspondence: Erkan Güvenç, M.D. Buca Seyfidemirsoy Devlet Hastanesi, Acil Servis Kliniği, İzmir, Turkey Tel: +90 232 - 220 10 15 E-mail: gvenerkan@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):373-383 DOI: 10.14744/tjtes.2019.93428 Submitted: 08.03.2019 Accepted: 15.08.2019 Online: 15.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Division: Spermatophya Subdivision: Angiospermae Class: Dicotyledoneae Subclass: Magnolipsida Family: Hypericaceae Genus: Hypericum Species: Hypericum Perforatum

Figure 1. St. John’s Wort (Hypericum perforatum).

necrosis except for hydrochloric acid.[3] The damage arises from acidic substances are located frequently in the pyloric region; if the stomach is congested, the acidic substances get mixed and cause disseminated tissue damage.[4,5] Although acidic substances cause the most damage in the stomach, in 6–10% of the cases, there are esophageal burns.[6] St. John’s Wort (SJW) plant is also known as Hypericum perforatum L. (Fig. 1) grows in Europe, Asia, North Africa and the United States for many years; it is used for many years as a medication for burns and poisonous animal bites.[7] The distal flowering branches of SJW are gathered when fresh, put into olive oil without delay; it is kept in a closed glass jar under the sunshine for 41 days; its color turns to deep red, and the final extract is used for medical purposes.[8] In the literature, there is not any clinical or experimental survey about the protective effects of the SJW extract on corrosive burns of esophagus or stomach. We investigated the possible protective effect of SJW on corrosive burns of esophagus and stomach.

MATERIALS AND METHODS Experimental Procedure This experimental study is performed after the ethical approvement from Dokuz Eylul University Medicine Faculty, Animal Ethics Committee with the protocol number of 65/2013; the survey is performed according to “The Guide for the Care and Use of Laboratory Animals-Institute of Laboratory Animal Resources Commission on Life Sciences National Research Council, USA”. The experimental part of the study is carried out in Dokuz Eylul University Multidisciplinary Experimental Research and Animal Laboratory; histopathological analyses were carried out in Ege University, Faculty of Medicine Division of Histology and Embryology; biochemical analyses were carried out in Ege University Science Faculty, Department of Biology and AREL Laboratory. The study is supported by Ege University Scientific Research Project Fund as project 2013TIP-079.

The Preparation of the Extract and Analyses of SJW The supranatant parts of the plant were collected and dried in the closed shade area. After drying, the material was ground homogenously by the mechanical grinder. The 6 gr of the powder was added to the glass balloon with 300 mL of 374

MeOH. We boiled the mixture firstly at 11ºC for 30 minutes then at 23ºC for 30 minutes with the ultrasonic bath. We covered the glass material with aluminium foil, providing a dark environment to protect the plant content. After the sonification samples are centrifuged at 7 G for 10 minutes; the supernatant part was taken another glass balloon; 300 mL MeOH was added to the remaining material again and the extraction steps were repeated from the beginning for four times. The extract was obtained by collected supernatant parts. MeOH was removed by evaporation. The lyophilizer system (Christ®) was used to remove the solvent completely. The final dry extract was put placed into stability control media with dry-flask bottles. The dry plant extract was dissolved with MeOH: Acetonitrile (1:1) after weighted; than, the 500 ppm samples were prepared. We used vortex and ultrasonic bath in order to obtain a homogenous solution. The samples filtered through injector fiilter were taken in HPLC vials and made ready for analyses. The injection amount was 20 μl. The chromatogram of the hyperphosphoric standard was 270 nM RT:50.80. The chromatogram of the pseudohyperigenin standard was 590 nM RT:44.89. The chromatogram of the hypericin standard was 590 nM RT: 53.73. The chromatograms for analyzes of the extracted sample were determined as 270 and 590 nm. The analyses were performed by the HPLC system consisting of Shimadzu SCL-10VP, manual sampler, column oven and DAD detector elements. We used Hicrom® C18 column with particle size 5 μm, 250 mm length and 4.6 mm diameter; and Hicrom® C18 anterior column with particle size 5 μm, 10 mm length and 4.6 mm diameter. The column oven temperature was 30ºC, the solvent flow rate was 1 mL/min and the detector wavelength 270 and 590 nm. The injection amount was 20 µl. The detailed SJW extract content is given in Table 1.

The Preparation of Oral Formulation, Including SJW A buffer solution is used, including 0.1 M acetic acid in a beaker. The beaker was placed on a calibrated pH-meter along with the mixer. The appropriate amount of 1M solution prepared with sodium hydroxide was added until the desired value was reached; then, the solution was taken into 100 mL balloon flask. The volume is completed by bidistillated water. The acetate buffer (pH=5) was prepared containing 12.5 mg/ Table 1. The chemical ingredents of St. John’s Wort extract Sample

RT

Area Mean area

SD

%RSD

Pseudohypericin 44.917 56.8

58.60

2.5456 4.34

Hypericin

49.034

36.8

38.05

1.7678 4.65

Hyperforin

51.122

96.6

97.10

0.7071 0.73

SD: Standard deviation; RSD: Relative standard deviation; RT: Reaction time.

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Table 2. Study groups Group 1 – Control (n=7)

We din’t do anything to this group

Group 2 – Burn (n=7)

A corrosive burn was made by 5% NaOH/0.2 ml but any treatment didn’t applied

Group 3 – Burn + SJW (n=7)

A corrosive burn was made by 5% NaOH/0.2 ml; and oral solution of SJW extract was given at

a dose of 50 mg/kg/day

Group 4 – Burn + Placebo (n=7)

A corrosive burn was made by 5% NaOH/0.2 ml; and a placebo gel was given at a dose of

50 mg/kg/day

Group 5 – Control SJW (n=7)

Oral solution of SJW extract was given at a dose of 50 mg/kg/day

Group 6 – Control Placebo (n=7)

A placebo gel was given at a dose of 50 mg/kg/day

SJW: St. John’s Wort.

mL SJW extract and 2% hydroxypropyl cellulose (HPMC) as the viscosity enhancer. The extract was taken at regular intervals into storage containers to avoid the inappropriateness of storage conditions.

The Preparation of Placebo Gel Extract The acetate buffer (pH=5) was prepared containing 12.5 mg/ mL SJW extract and 2% hydroxypropyl cellulose (HPMC) as the viscosity enhancer. The extract was taken at regular intervals into storage containers to avoid the inappropriateness of storage conditions.

The Subject Groups and Experimental Method We used 42 male and female Wistar albino rats weighing between 200–300 gr. The rats were kept under normal day&night cyclus far from noise at 20–22ºC for adaptation. They were fed by tap water and standard artificial mouse feed ad libitum. The base of the cage consisted of wood dust. The alkaline corrosive material was 5% NaOH/0.2 cc consistent with Katrancioglu et al.’s[9] study. The groups and their specifications are explained in Table 2. Five minutes before the corrosive application, intraperitoneal ketamine (Pfizer- Ketalar®; 50 mg/mL ketamine hydrochloride) 0.3–1.3 ml/kg was applied for sedation and analgesia without losing swallowing function. The corrosive material was given to the subjects in group 1, 2, 3 and 4 using mouth, which was ending at the level of the cervical esophagus. The admission time was nearly 20 minutes after oral ingestion of corrosive materials. Thus, we applied the placebo and SJW extract 20 minutes after the corrosive material application by feeding tube. The treatment and placebo applications were repeated every day for once for 14 days. To achieve analgesia, we applied acetaminophen 2 mg/mL (Bristol-Myers Squibb-Perfalgan®; 10 mg/mL acetaminophen). The subjects were sacrificed in the 15th day; tissue samples were derived from 3 cm proximal of the esophagogastric junction, stomach and liver.

Histopathologic Evaluation

homogenised over ice in the homogenized buffer (50 mm phosphate buffer, pH:7.4) with a mechanic homogenizer (Heidolph Silent Crusher M). The samples were fixated by 4% formaldehyde; the 5 µm slices were stained by hematoxylin -eosin or Mallory Azan Stain. The histopathologic examination was performed by a histologist under X10, X20, X40 magnification without knowing the groups.[10] The stenosis index was calculated by determining the esophagus wall thickness and lumen diameter.[10–13] The submucosal cologen accumulation, muscularis mucosa damage, muscular layer damage and collagen accumulation in the muscular layer of esophagus were evaluated. The collagen accumulation level was determined between 0–5 according to the histopathologic scoring system showed in Table 3.[10,12,13] The gastric tissue samples were derived by dissection of the greater curvature of the stomach and getting the stained parts of the adjacent part of the corpus. The mucosal PMNL Table 3. Histopathologic scoring of the esophagus[10,12,13]

Score

Submucosal collogen accumulation Absent

0

Mild (equal or less than 2 folds of the

1

muscularis mucosa)

Severe (more than 2 folds of the muscularis

2

mucosa) Muscularis mucosa damage Absent

0

Present

1

Tunica muscularis damage and collogen accumulation Absent

0

Mild (collogen accumulation aroun muscle fibers)

1

Severe (mild damage and collogen accumulation 2

takes some of the fibers place)

Total score

0–5

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infiltration, mucosal edema, gastric gland dilatation and submucosal PMNL infiltration were performed.

Cytotoxicity Analyses We used the malonedialdehyde (MDA) level to determine the peroxidation level of the lipid inside the cell membrane, superoxide dismutase (SOD) level for free oxygen radicals and the level of glutathione peroxidase (GPX) and catalase (CTX) levels for their tissue-protective effects.[14] The in-vitro cytotoxicity of the SJW was determined by the dermal fibroblast tissue line (HDFa, Gibco Invitrogen cell culture, C-013-5C). The frozen cells were cultured in RPMI (10% FBS, 100 U/mL penicillin and 100 μg/mL streptomycin) agar at 37°C, including 5% CO2. The number of the fifth passage fibroblasts were used for cytotoxicity determination. The vitality of the cells was determined by MTT (Sigma In Vitro Toxicology Assay Kit, MTT based) vitality test and probit analyses was performed using the SPSS v.20 package program.

Statistical Method SPSS 20.0 (IBM Corporation, Armonk, New York, United States) program was used to analyze the data. Continuous variables were expressed as mean±sd if they are normally distributed and expressed as median (min-max) if not. Normal distribution was determined by histogram and One-Sample Kolmogorov Smirnov test. To determine the difference of continuous variables between groups, nonparametric tests are used due to the low sample size; the Mann Whitney-U test for two groups and the Kruskal Wallis

test for more than two groups. The difference of the cathegorical variables between groups are determined using the Chi-square test and Fisher’s exact test. P<0.05 was accepted as significant.

RESULTS Weight Analysis Results All subjects in the Groups (n=42) were divided in a manner that each group contained seven subjects. Their weights were measured before the process. No statistically significant difference in weight was found between the groups in everyday weight. In time, every group get weight significantly except Group 5 (p<0.05).

Esophageal Histopathologic Findings The microscopic specifications of the esophageal tissue microscopy are shown in Figure 2. Group 2 – Alkaline burn group: Diffused or focal mucosal erosion. There were moderate edema and sporadic mucosal neutrophil infiltration infiltration in the submucosa. Submucosal and mucosal collagen accumulation, inflammation and edema were detected. There were significant tissue damage and constriction in the lumen (Fig. 2b). Group 3 – Alkaline burn + SJW group: Moderate inflammation in all layers, mucosal and submucosal edema were detected. If we compare with Group 2, focal erosion findings, submucosal collagen accumulation, mucosal collagen accumulation, and stenosis index were lesser than Group 2 (Fig. 2c).

(a)

(b)

(c)

(d)

(e)

(f)

Figure 2. The histopathologic appearence of the esophagus. H&E stain; X40 magnification (X40=125µm); the red arrows are stratum corneum. Blue arrows are stratum basale layer of epidermis; (a) Control group; (b) Burn Group; (c) Burn and SJW group; (d) Burn and placebo group; (e) SJW without burn group; (f) Placebo without burn group.

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Group 4 – Alkaline burn + Placebo group: Similarly with Group 2, diffused or focal mucosal erosion; mild edema and sporadic mucosal neutrophil infiltration in submucosa; submucosal and mucosal collagen accumulation, inflammation and edema were detected. There are significant tissue damage and constriction in the lumen (Fig. 2d).

Group 6 – Control + Placebo group: The appearance was similar to Group 1 and 5. There are mild edema and inflammation in the mucosa. Minimal inflammation and edema in the submucosa. The mucosal histopathologic examination was normal (Fig. 2f).

Group 5 – Control + SJW group: There were mild edema and inflammation in mucosa, but not diffused erosion findings. Minimal inflammation and edema were present in the submucosa. The mucosal histopathologic examination was normal (Fig. 2e).

The frequency of the histopathologic findings of all groups is expressed in Table 4 in detailed. Submucosal collagen accumulation of esophagus in Group 3 was similar to Group 1 (p=0.559), significantly higher in Group

Table 4. The frequency of the histopathologic features of the groups

Experiment groups Group 1

Group 2

Group 3

Group 4

Group 5

Group 6

n % n % n % n % n % n %

Submucosal collogen accumulation of esophagus Absent Mild Severe

6 85.7 – – 4 57.1 1 14.3 6 85.7 4 57.1 1 14.3 2 28.6 3 42.9 4 57.1 1 14.3 3 42.9 – – 5 71.4 – – 2 28.6 – – – –

Muscularis mucosa damage of esophagus Absent Present

6 85.7 2 28.6 6 85.7 2 28.6 4 57.1 6 85.7 1 14.3 5 71.4 1 14.3 5 71.4 3 42.9 1 14.3

Tunica muscularis damage and collogen accumulation in esophagus Absent Mild Severe

7 100 – – 6 85.7 2 28.6 7 100 7 100 – – 3 42.9 1 14.3 2 28.6 – – – – – – 4 57.1 – – 3 42.9 – – – –

PMNL infiltration and mucosal in gastric mucosa Absent Mild Moderate Severe

6 85.7 – – 1 14.3 – – 5 71.4 4 57.1 1 14.3 2 28.6 3 42.9 3 42.9 2 28.6 3 42.9 – – 2 28.6 2 28.6 2 28.6 – – – – – – 3 42.9 1 14.3 2 28.6 – – – –

Gastric mucosal edema Absent Mild Moderate Severe

6 85.7 – – 3 42.9 1 14.3 2 28.6 4 57.1 1 14.3 3 42.9 2 28.6 2 28.6 5 71.4 2 28.6 – – 3 42.9 2 28.6 4 57.1 – – 1 14.3 – – 1 14.3 – – – – – – – –

Gastric gland dilatation Absent Mild Severe

5 71.4 – – 1 14.3 – – 4 57.1 4 57.1 2 28.6 3 42.9 4 57.1 4 57.1 3 42.9 3 42.9 – – 4 57.1 2 28.6 3 42.9 – – – –

Submucosal PMNL infiltration in stomach Absent Mild Moderate Severe

5 71.4 – – 2 28.6 1 14.3 5 71.4 5 71.4 2 28.6 2 28.6 3 42.9 2 28.6 2 28.6 2 28.6 – – 3 42.9 2 28.6 3 42.9 – – – – – – 2 28.6 – – 1 14.3 – – – –

PMNL: Polymorphonuclear lymphocytes.

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2 than Group 1 (p=0.005); higher in Group 4 than Group 3 but there was not any statistical significance (p=0.266). Consequently, SJW has a significant effect on degreasing the submucosal collagen accumulation of esophagus and also it is better than placebo. Muscularis mucosa damage in esophagus in Group 2 was higher than Group 1 but lack of statistical significance (p=0.103); similar in Group 3 and 1 (p=1.000); higher in Group 2 than Group 3 but lack of statistical significance (p=0.103); similar in Group 4 and 2 (p=1.000). Consequently, SJW has a significant effect on degreasing the muscularis mucosa damage in esophagus also it is better than placebo. Tunica muscularis damage and collagen accumulation in esophagus was significant in Group 2, which was higher than the control group (p=0.001), similar in Group 3 and 1 (p=1000); higher in Group 4 than Group 1 (p=0.021). Consequently, SJW has a significant effect on degreasing the tunica muscularis damage and collagen accumulation in esophagus. Also, it is better than placebo.

Gastric Histopathologic Findings The microscopic spesifications of the gastric tissue microscopy are shown in Figure 3.

PMNL infiltration in gastric mucosa was higher in Group 2, 3 and 4 than Group 1 (p-values are 0.005, 0.029, 0.005, respectively); similar in Group 3 and 2 (p=1.000). Edema in gastric mucosa was higher in Group 2 than Group 1 (p=0.005); similar in Group 3 and 1 (p=0.266); similar in Group 4 and 3 (p=0.559). Consequently, SJW has a significant effect on degreasing the edema in gastric mucosa and also similar with placebo. Dilatation in gastric gland was higher in Group 2 than Group 1 (p=0.021); similar in Group 3 and 1 (p=0.103); similar in Group 4 and 3 (p=1.000). Consequently, SJW has a significant effect on degreasing the dilatation in the gastric gland and also similar to placebo. PMNL infiltration in gastric submucosa was higher in Group 2 than Group 1 (p=0.021); similar in Group 3 and 1 (p=0.286); similar in Group 4 and 1 (p=0.103); similar in Group 4 and 3 (p=1.000). Consequently, SJW has a significant effect on degreasing the dilatation in the gastric gland and also similar with placebo. Consequently, SJW has a significant effect on degreasing the PMNL infiltration in gastric submucosa and also similar to placebo. The mean stenosis index, epithelium thickness and comparison of them are given in Table 5. The stenosis index was

(a)

(b)

(c)

(d)

(e)

(f)

Figure 3. The histopathological appearance of all groups. The blue arrows indicate superficial mucosal layer and mucus cells. The red arrows are foveola gastricea, the red stars are the dilatation of the gastric glands, yellow stars are the PMNL cells accumulation areas. (a) Control group; X40 magnification, essential cells; (b) Burn Group; X20 magnification, mild dilatation of gastric glands and capillary hemorhagia, submucosal PMNL infiltration, edema and congestion in vessels; (c) Burn and SJW group; X20 magnification, submucosal PMNL infiltration, edema and congestion in vessels; (d) Burn and placebo group; X20 magnification, moderate dilatation in gastric glands and capillary hemorhagia, submucosal PMNL infiltration, edema and congestion in vessels; (e) SJW without burn group; X40 magnification, partial mucosal damage and decrease in mucus accumulation; (f) Placebo without burn group; X40 magnification. (X20=250 µm, X40=125 µm).

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Table 5. Stenosis index and epithelium thickness of the groups

Stenosis index Mean±SD (micrometer)

Group 1

0.12±0.01

Epithelium thickness

Comparison (p) Group 2

Mean±SD (micrometer)

Group 3

0.002 0.002

Group 2 0.42±0.03

– 0.002

160.49±3.10 66.76±2.76

Comparison (p) Group 2

Group 3

0.002 0.002 – 0.002

Group 3 0.22±0.02

0.002 –

127.70±3.82

0.002 –

Group 4

0.38±0.03

0.029 0.002

101.06±2.52

0.002 0.002

Group 5

0.23±0.03

0.002 0.698

157.67±2.72

0.002 0.002

Group 6

0.20±0.03

0.002 0.120

158.02±1.51

0.002 0.002

SD: Standard deviation.

higher in the SJW group (Group 3) than the control group but lower than the burn group (Group 2) and placebo (Group 4). Contrary, epithelium thickness was lower in the SJW group (Group 3) than the control group but higher than burn group (Group 2) and placebo (Group 4). Consequently, from the point of stenosis index, epithelium thiskness, SJW has a significant effect on degreasing the stenosis index and protecting the decrease in epithelium thickness due to alkaline burn and better than placebo. MTT cell vitality test is calculated: LC50 = 2580564,906 µg/ml = 2580.564 mg/ml = 2.580564 gr/ml. The formulation of the medication is applied as 50 mg/kg. The amount of active ingredient in the oral formulation was 12.5 mg/mL, which was very low than the calculated LC50 value. Consequently, the SJW extract has no cytotoxicity on fibroblasts.

The Enzyme Levels in Groups The MDA, CAT, SOD and GPX levels in groups are expressed in Table 6. MDA and CAT levels were different in groups, but

SOD and GPX levels were similar in all groups. The box-blot graphs of all groups are given in Figure 4. The MDA level was higher in Group 2 than Group 1 (p=0.048), but CAT levels were similar in Group 1 and 2 (p=0.701). Additionally, the MDA level was higher in Group 3 than Group 2 (p=0.001), but CAT levels were similar in Group 2 and 3 (p=0.200). If we compare with placebo, the MDA level was similar in Group 2 and 4 (p=0.949), but CAT levels were lower in Group 4 than Group 3 (p=0.001). The MDA and CAT levels were higher in Group 3 than group 4 (p-values are 0.001 and 0.002, respectively). As a summary, we can say that the peroxidation level of the lipid inside the cell membrane, which is determined by MDA, was higher in the SJW group than the burn group and also placebo. Additionally, the tissue-protective effects which were determined by CTX was similar in SJW and burn group, but the SJW group was higher than placebo.

DISCUSSION SJW extract has been used for many years.[15] Previous stud-

Table 6. Mean enzyme levels in all of he groups

MDA (nmol/mg protein)

CAT (U/mg protein)

SOD (u/mg protein)

GPX (U/mg protein)

Mean±SD Mean±SD Mean±SD Mean±SD

Group 1

1.41±0.13

71.43±3.95

86.29±3.45

12.34±0.57

Group 2

1.56±0.11

71.0±8.64

85.14±2.79

12.16±0.66

Group 3

1.89±0.12

65.43±6.95

86.29±3.82

12.41±0.58

Group 4

1.57±0.08

56.14±2.54

83.57±2.76

11.67±1.11

Group 5

1.70±0.10

66.29±6.10

86.00±3.11

12.66±0.93

Group 6

1.39±0.09

60.29±3.20

83.43±2.37

12.81±0.75

p <0.001 0.001 0.249 0.200 SD: Standard deviation; MDA: Malonedialdehyde; CAT: Catalase; SOD: Superoxide dismutase; GPX: Glutathione peroxidase.

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80

2.200

75 CAT (U/mg protein)

MDA (nmol/mg protein)

2.000

1.800

1.600

1.400

70 38

65 70 55

1.200

8

50 Group 1 Group 2 Group 3 Group 4 Group 5 Group 6

Group 1 Group 2 Group 3 Group 4 Group 5 Group 6 16.00

100 95

85 80

31

GPX (U/mg protein)

SOD (U/mg protein)

14.00 90

24

12.00 3

10.00

75 8.00

70 Group 1 Group 2 Group 3 Group 4 Group 5 Group 6

Group 1 Group 2 Group 3 Group 4 Group 5 Group 6

Figure 4. The MDA, CAT, SOD and GPX levels in groups. MDA: Malonedialdehyde; CAT: Catalase; SOD: Superoxide dismutase; GPX: Glutathione peroxidase.

ies have investigated the beneficial effects of this extract on thermal burns and traumatic injuries; its useful effects on the healing of linear and circular lacerations; it also shortens the re-epithelisation time.[16] Additionally, SJW extract protects epithelium thickness and reduces the degeneration of hair follicles in thermal burns.[15] In Burning Mouth Syndrom, to use SJW three times a day in 300 mg dose for 12 weeks reduce the burning sensation, but it does not benefit the pain sensation.[17] The pharmacologic studies with SJW are generally about the antidepressant effect using the ingredients of the plant called hypericin and hyperforin. The flower and branch part of the plant include 2–4.5% hyperforin and 0.2–1.8% adhiperforin which are a branch of phloroglucinol group; the flower and buds of the plant include 0.05–0.3% naftodiantron; the parts of the plant over the ground like leaves, stalks, flowers and buds include 2–4% flavonoids.[18] The plant extract is used as antidepressant, antitumor, antiviral, antimicrobial, antibacterial, analgesic, hepatoprotective and gastroprotective purposes.[19–28] It is argued that the extract could be used as antiviral in acquired immune deficiency syndrome (AIDS).[29] 380

According to some of the in-vitro studies, the ingredients of SJW inhibits some of the steps in inflammatory reactions. [26,30,31] The SJW extract inhibits the free radical production, myeloperoxidase, cyclo-oxygenase-1, 5-lipo-oxygenase and inducible cyclo-oxygenase and nitric oxide synthase.[32–34] The first treatment method of the strictures due to corrosive esophagus burn is the antegrade dilatation of the esophagus with oiled whalebone in the 17th century; the rubber dilatators are first used in 1837 for the same purpose; it was developed by contrast-enhanced radiologic studies after the discovery of bismuth in 1895; finally, a new era is started with the invention of distally illuminated esophagoscope by Chevalier Jackson in 1902.[35–37] The cases with esophageal stricture due to corrosive burns were reduced by the prophylactic use of the antibiotics in the 1940s, also using steroids and earlyprophylactic dilatation in the 1950s.[35,36] While the endoscopic examination of the corrosive esophageal burns, deep burns, massive hemorrhagia, ulceration, focal necrosis and simple inflammation findings could be seen.[38] The protective effects of colchicine was reported Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


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in the animal experiment.[39] N-acetyl cysteine was used due to the intermolecular disulfide bond feature, but its clinical usage is precluded because of excessive bronchial secretion. [40] Indomethacin was tried for its anti-inflammatory effect, but it was not advised due to its inhibitory effect of thrombocyte aggregation.[39] The experimental studies reported the protective effect of antioxidant substances like vitamin E and C in stricture formation by reducing collagen synthesis.[41] Epidermal growth factor (EGF) and interferon γ (IFN–γ) are significantly reduce the residual stenosis rate after corrosive esophageal burns.[42] As we see, various experimental methods are tried to reduce the stenosis due to corrosive esophageal burns. However, the desired clinical target and clinical usage could not be achieved because the treatment method generally could not be applied in clinical practice and also there are not enough clinical human studies. To our knowledge, there is not any research into the effects of SJW in corrosive esophageal burns. Thus, we could not compare all of the data results obtained in previous studies. In our study, mucosal edema and collagen accumulation in the epithelium, diffuse edema, inflammation and collagen accumulation were detected in the burn model group. The benefits of SJW and the comparison with placebo were investigated in this study. When we gave the SJW extract to the burn model, submucosal and mucosal inflammation, edema, focal erosion and collagen accumulation were reduced and also it was superior to placebo. Also, the muscularis mucosa damage and collagen accumulation were lower than burn and placebo group. The collagen accumulation between muscle fibers and stenosis index was lower in the SJW treatment group, and also epithelium thickness was higher in the SJW group than placebo group. PMNL infiltration in gastric mucosa, gastric mucosal edema, gastric gland dilatation was lower in the SJW group than the burn group. The anti-oxidant activity of the SJW, which is rich in flavonoids, is showed in-vitro.[43] With the use of the medium (75 mg/kg of body weight/day) or high (150 mg/kg of body weight/day) dose, SJW reduces the malondialdehyde levels in plasma or liver of rats fed by cholesterol reach diet.[43] Intraperitoneal single dose (50 mg/kg) SJW administration for 15 minutes to rats with hepatic ischemia reduces the liver enzymes and malondialdehyde and increases catalase activity.[44] The medications that will be applied to the gastrointestinal system should be safe for the patient. While the application of SJW to chicken embryo cells, active fibroblast cells get into polygonal shape and fibroblasts cell production increases.[45] In our study, the lethal concentration of the extract is determined as 2.580564 gr/ml; the amount of active ingredient in the oral formulation was 12.5 mg/mL, which was very low than the calculated LC50 value. Thus, our findings suggest that our extract is safe for using in the gastrointestinal system. Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

SJW has lower side effects in normal doses. The most frequently seen side effects are gastrointestinal symptoms, allergic reactions, vertigo, confusion, discomfort, apathy and xerostomia.[46,47] These effects are generally mild, moderate and transient.[48] The side effects are dose-dependent and also the medications that the patient had already using may affect the side effects.[46,47,49–52] SJW extracts have no genotoxic potential or mutagenic activity, according to in-vivo and in-vitro studies, but acute toxic neuropathy and mania are reported.[46,53] In conclusion, SJW has protective beneficial effects on corrosive esophageal burns in the early phase. Its lethal concentration is very high, so it can be used safely in corrosive burns in esophagous. However, we should be careful while using the extract in humans. There is not any human model; only with further human studies can detect the benefits and harms of SJW on the gastrointestinal system. Ethics Committee Approval: This experimental study is performed after the ethical approvement from Dokuz Eylul University Medicine Faculty, Animal Ethics Committee with the protocol number of 65/2013. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: E.G., S.K.; Design: E.G.; Supervision: S.K.; Fundings: E.G., Y.U., E.Ö.Ç.; Materials: E.G., Y.U., T.Ç., F.K.; Data: E.G., F.K., B.G.; Analysis: E.G., Y.U; Literature search: E.G., S.K., Y.U., T.Ç; Writing: E.G.; Critical revision: E.G. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

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31. Abdel-Salam OM. Anti-inflammatory, antinociceptive, and gastric effects of Hypericum perforatum in rats. ScientificWorldJournal 2005;5:586–95. 32. Pabuçcuoğlu A, Konyalioğlu S, Baş M, Meral GE. The in vitro effects of Hypericum species on human leukocyte myeloperoxidase activity. J Ethnopharmacol 2003;87:89–92. 33. Albert D, Zündorf I, Dingermann T, Müller WE, Steinhilber D, Werz O. Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase. Biochem Pharmacol 2002;64:1767−75. 34. Tedeschi E, Menegazzi M, Margotto D, Suzuki H, Förstermann U, Kleinert H. Anti-inflammatory actions of St. John’s wort: inhibition of human inducible nitric-oxide synthase expression by down-regulating signal transducer and activator of transcription-1alpha (STAT-1alpha) activation. J Pharmacol Exp Ther 2003;307:254–61. 35. Tucker JA, Yarington CT Jr. The treatment of caustic ingestion. Otolaryngol Clin North Am 1979;12:343–50. 36. Ulman I, Mutaf O. A critique of systemic steroids in the management of caustic esophageal burns in children. Eur J Pediatr Surg 1998;8:71–4. 37. Jackson C. Bronchoscopy: Past, present and future. J Med N Engl 1928;199:758−63. 38. Di Costanzo J, Noirclerc M, Jouglard J, Escoffier JM, Cano N, Martin J, et al. New therapeutic approach to corrosive burns of the upper gastrointestinal tract. Gut 1980;21:370−5. 39. Thompson JN. Corrosive esophageal injuries. II. An investigation of treatment methods and histochemical analysis of esophageal strictures in a new animal model. Laryngoscope 1987;97:1191–202. 40. Liu AJ, Richardson MA. Effects of N-acetylcysteine on experimentally induced esophageal lye injury. Ann Otol Rhinol Laryngol 1985;94:477– 82. 41. Günel E, Cağlayan F, Cağlayan O, Akillioğlu I. Reactive oxygen radical levels in caustic esophageal burns. J Pediatr Surg 1999;34:405–7. 42. Berthet B, di Costanzo J, Arnaud C, Choux R, Assadourian R. Influence of epidermal growth factor and interferon gamma on healing of oesophageal corrosive burns in the rat. Br J Surg 1994;81:395–8. 43. Zou Y, Lu Y, Wei D. Hypocholesterolemic effects of a flavonoid-rich extract of Hypericum perforatum L. in rats fed a cholesterol-rich diet. J Agric Food Chem 2005;53:2462–6. 44. Bayramoglu G, Bayramoglu A, Engur S, Senturk H, Ozturk N, Colak S. The hepatoprotective effects of Hypericum perforatum L. on hepatic ischemia/reperfusion injury in rats. Cytotechnology 2014;66:443–8. 45. Oztürk N, Korkmaz S, Oztürk Y. Wound-healing activity of St. John’s Wort (Hypericum perforatum L.) on chicken embryonic fibroblasts. J Ethnopharmacol 2007;111:33–9. 46. Barnes J, Anderson LA, Phillipson JD. St John’s wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties. J Pharm Pharmacol 2001;53:583–600. 47. Greeson JM, Sanford B, Monti DA. St. John’s wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature. Psychopharmacology (Berl) 2001;153:402–14. 48. Ernst E, Rand JI, Barnes J, Stevinson C. Adverse effects profile of the herbal antidepressant St. John’s wort (Hypericum perforatum L.). Eur J Clin Pharmacol 1998;54:589–94. 49. Izzo AA. Drug interactions with St. John’s Wort (Hypericum perforatum): a review of the clinical evidence. Int J Clin Pharmacol Ther 2004;42:139–48. 50. Mannel M. Drug interactions with St John’s wort : mechanisms and clinical implications. Drug Saf 2004;27:773–97. 51. Di YM, Li CG, Xue CC, Zhou SF. Clinical drugs that interact with St. John’s wort and implication in drug development. Curr Pharm Des 2008;14:1723–42. 52. Zhou SF, Lai X. An update on clinical drug interactions with the herbal antidepressant St. John’s wort. Curr Drug Metab 2008;9:394–409. 53. Nierenberg AA, Burt T, Matthews J, Weiss AP. Mania associated with St. John’s wort. Biol Psychiatry 1999;46:1707–8.

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Güvenç et al. The healing effects of Hyperium perforatum on experimental alkaline corrosive eosephageal and stomach burns

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Deneysel alkali koroziv ösefageal ve mide yanıklarında Hyperium perforatum’un (Sarı Kantaron) iyileştirici etkisi Dr. Erkan Güvenç,1 Dr. Selahattin Kıyan,2 Dr. Yiğit Uyanıkgil,3 Dr. Emel Öykü Çetin,4 Dr. Fatih Karabey,5 Dr. Türker Çavuşoğlu,3 Dr. Burak Gökçe6 Buca Seyfidemirsoy Devlet Hastanesi, Acil Servis Kliniği, İzmir Ege Üniversitesi Tıp Fakültesi Hastanesi, Acil Tıp Anabilim Dalı, İzmir Ege Üniversitesi Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, İzmir 4 Ege Üniversitesi Eczacılık Fakültesi, Farmasötik Teknoloji Anabilim Dalı, İzmir 5 Ege Üniversitesi Fen Bilimleri Enstitüsü, Biyoteknoloji Anabilim Dalı, İzmir 6 Ege Üniversitesi Fen Fakültesi, Biyoloji Anabilim Dalı, İzmir 1 2 3

AMAÇ: Koroziv yanıklarda en sık etiyolojik neden alkali maddelerdir. Hypericum Perforatum’un deneysel özofagus ve mide alkali koroziv yanık modelinde etkili olup olmadığı araştırıldı. GEREÇ VE YÖNTEM: Araştırmada 42 adet, 200–300 gram ağırlığında, Wistar Albino sıçanlar seçildi ve 6 grup oluşturuldu; Grup 1: Kontrol, Grup 2: Yanık+SF (YSF), Grup 3: Yanık+Kantaron (YK), Grup 4: Yanık+Plasebo (YP), Grup 5: Kantaron (K), Grup 6: Plasebo (P). Tedavi sonrasında 15. gün diseksiyon uygulanarak alınan özofagus, mide ve karaciğer doku örneklerinden, histopatolojik ve biyokimyasal belirteçlere (SOD, GPX, MDA, CAT) bakıldı. Uygulanan ilaç formulizasyonunun fibroblastlar üzerine sitotoksitesi invitro koşullarda erişkin insan dermal fibroblast hücre hattında değerlendirildi (HDFa, Gibco invitro hücre kültürü, C-013-5C). BULGULAR: Deneklerin ağırlık değerlerinin karşılaştırmasında Grup 1, 3, 4 ve 6 da ağırlık artış, Grup 2’de ağırlık kaybı saptandı, Grup 5’te ise anlamlı bir fark saptanmadı. YK grubunda özefagusta submukozal kollojen birikimi, muskularis mukoza hasarı, tunika muskularis hasarı ve kollojen akümülasyonu kontrol grubu ile benzerdi, fakat YSF ve plasebodan daha azdı. Midede mukozal hasar, gastrik bez dilatasyonu, submukozal PMNL infiltrasyonu YK grubunda kontrol grubu ile benzer ve YSF grubundan daha az idi. Kantaronun letal kosantrasyonu 2.58 gr/mL idi. TARTIŞMA: Kantoron özefagus ve midenin orta derecede alkali koroziv yanıklarında subakut periyotta korumada etkilidir. Kantaronun gastrointestinal sistemin koroziv yanıklarında kullanılabileceği akılda tutulmalıdır. Anahtar sözcükler: Alkali; Hypericum Perforatum; koroziv; Saint John’s Wort; yanık. Ulus Travma Acil Cerrahi Derg 2020;26(3):373-383

doi: 10.14744/tjtes.2019.93428

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ORIGIN A L A R T IC L E

Hem-o-lok clips versus intracorporeal knotting for the closure of the appendix stump in laparoscopic appendectomy: A prospective randomized study Orhan Üreyen, M.D., Sedat Tan, M.D., Emrah Dadalı, M.D., Mehmet Yıldırım, M.D., Enver İlhan, M.D. Department of General Surgery, Universty of Health Sciences, İzmir Bozyaka Training and Research Hospital, İzmir-Turkey

ABSTRACT BACKGROUND: In this study, we aimed to evaluate the superiority of intracorporeal sutures and Hem-o-lok clips about efficiency, reliability and cost. METHODS: We performed laparoscopic surgery for acute appendicitis in this study. Appendiceal stump was closed by Hem-o-lok clips (Group I) and intracorporeal knotting (Group II) in a randomized manner. Groups were compared for demographic data (age, sex, body mass index, American Society of Anesthesiologists score) operation time, total cost, 2.6.12.24.hours and 7th day pain score. RESULTS: Demographic data, such as age, gender and BMI, were similar between groups (p>0.05). There was no significant difference between the groups concerning peroperative and postoperative complications (p>0.05). No postoperative nausea, vomiting, ileus and intraabdominal abscess were observed in patients. There was no significant difference between the groups about duration of operation, length of hospital stay and cost analysis (p>0.05). There was no significant difference in pain scores of groups. The effect of the operation type on pain scores was not statistically significant (p>0.05). CONCLUSION: This study showed that both intracorporeal knotting and Hem-o-loc clips were effective, reliable and similar costeffective in laparoscopic appendectomy. The decision should be based on the surgeon’s experience. Keywords: Appendicitis; cost-effectiveness; laparoscopic surgery.

INTRODUCTION Acute appendicitis is a health problem affecting a significant part of the population. Although antibiotic treatment can be applied in very few selected cases, the main treatment method is surgery.[1] Open appendectomy is an easy and safe method in surgical treatment. The other surgical treatment method is laparoscopic appendectomy. Because of its advantages, such as less postoperative pain, faster recovery, shorter hospital stay and better visualization of lower abdominal quadrants, laparoscopic appendectomy is getting used more commonly nowadays.[2] Recent guidelines recommend laparoscopic appendectomy as the first choice for the treatment of acute appendicitis.[3,4] The critical step

of this surgery is the closure of the appendix stump, which may lead to very serious postoperative complications when not closed properly.[5] In laparoscopic surgery, the appendix stump can be closed by different methods, such as endostapler,[6] endoloop, metal clip[5] bi-polar endocoagulation,[7] Hem-o-lok clips[8,9] and intracorporeal knotting.[10] Each method has advantages and disadvantages.[5,11] Current studies are inadequate about cost, postoperative pain scale and recovery time.[1] Therefore, the proper closure method of the appendix stump in laparoscopic appendectomy has not been decided yet. Recently, hem-o-lok clips have become quite popular in the closure of the appendix stump.[9,12,13] On the other hand, intracorporeal knotting is the other closure method that is safe and relatively inexpensive.[1,10,14–16]

Cite this article as: Üreyen O, Tan S, Dadalı E, Yıldırım M, İlhan E. Hem-o-lok clips versus intracorporeal knotting for the closure of the appendix stump in laparoscopic appendectomy: A prospective randomized study. Ulus Travma Acil Cerrahi Derg 2020;26:384-388. Address for correspondence: Orhan Üreyen, M.D. Sağlık Bilimleri Üniversitesi, İzmir Bozyaka Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İzmir, Turkey Tel: +90 232 - 250 50 50 E-mail: drureyen@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(3):384-388 DOI: 10.14744/tjtes.2019.02248 Submitted: 21.05.2019 Accepted: 17.11.2019 Online: 14.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Ureyen et al. Hem-o-lok clips versus intracorporeal knotting for the closure of the appendix stump in laparoscopic appendectomy

In our study, we aimed to evaluate the superiority of intracorporeal sutures and Hem-o-lok clips concerning efficiency, reliability and cost.

MATERIALS AND METHODS Laparoscopic appendectomy was performed in patients with acute appendicitis. The closure of the appendix stump was randomized before the operation. Appendiceal stump was closed with Hem-olok clips (Group I) and intracorporeal knotting by 2/0 silk (Katsan, Izmir, Turkey) (Group II). All expenses included in total cost from the admission to emergency room until the time of discharge. Groups were compared for demographic data (age, sex, body mass index (BMI) American Society of Anesthesiologists score (ASA), operation time, total cost, 2.6.12.24. hours and 7th day pain score. The pain score was evaluated using the visual analog scale (VAS). Tramadol hydrochloride 100 mg (Menta Farma, Istanbul, Türkiye)R used for postoperative analgesia. Patients with an appendiceal stump higher than 10 mm in diameter, under 18 years of age, and other pathology in addition to appendiceal pathology were excluded from this study. The primary endpoint of this study was the significant difference between the groups concerning morbidity and mortality in the early period. Our study was planned in accordance with the Helsinki Declaration and the informed consent of the patients was obtained. This study is registered retrospectively on the clinicaltrials. gov database and approved by the Ethics Committee of University of Health Sciences, Izmir Bozyaka Training and Research Hospital (decision date: 24.03.2015-no:3). Power analysis was carried out to determine the minimum sample size. (1b)=0.80 power with a probability value of a=0.05. This analysis suggested that the sample size should be a minimum of 16 patients in each group. After We explained the details of the surgical procedure to the participants and obtained their written informed consent. The patients were randomized by a coin toss. IBM SPSS Statics Version 24 was used for the statistical analysis of the data. In the comparison of categorical data between groups, Fisher’s Whits Exact test was used. Mann-Whitney U test in the comparison of continuous data between groups was used. Repeated Measures ANOVA statistical analysis was used in comparing pain scores. P<0.05 was considered statistically significant.

Surgical Method All operations were performed by two surgeons. Prophylactic antibiotic (100 ml (500 mg) Metronidazole IV Infusion) was performed 30 min before the operation. The first 10 mm trocar was inserted above the umbilicus using Hasson technique and pneumoperitoneum was formed. 5 mm trocar was inserted at the suprapubic region, and 10 mm trocar was inUlus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

serted at the left lower quadrant under direct vision. 15–20° Trendelenburg and 10–15° left side position was given to the operation table. Appendix meso was dissected and coagulated. For hem-o-lok group 2 clips applied in the stump side and one clip for the appendix side. Then, cut with endoscissors between them. The appendix was taken out of the abdomen inside an endobag. For intracorporeal knotting group, 2/0 multiflaman silk was used. Two for the stump side and one for the appendix side were used. Again using an endobag, the specimen was taken out. In both groups, 10 mm trocar entrance fascia closed with 0 polyglactin and skin closed with 3/0 polypropylene.

RESULTS In our study, 41 patients met the inclusion criteria. 20 patients for group 1 and 21 for group 2. Randomization protocol is given in Figure 1. Demographic data, such as age, gender and BMI, were similar between groups (p>0.05) (Table 1). Perop complications were in one patient. Hemoo-lok clip bit the cekum. No events seen in the follow-up period and discharged at day 6. In Group II, no complication seen peroperatively. For postoperative complications, group 1 was uneventfully. In group 2, postoperative complications were seen in three cases, including fever, right shoulder pain and wound infection. There was no significant difference between the groups concerning peroperative and postoperative complications (p>0.05). No postoperative nausea, vomiting, ileus and intraabdominal abscess were observed in patients. There was no significant difference between the groups about duration of operation, length of hospital stay and cost analysis (p>0.05) (Table 2). There was no significant difference in 2–6–12–24–36th hour and 7th day pain scores of groups (p>0.05) (Table 3). Repeated Measures ANOVA analysis results were evaluated for the relationship between the operation type and the pain scores in 2–6–12–24–36th hour and 7th day. The decrease in pain by time was found 1074 Patients with apendectomies from 2015–2018

95 Patients laparoscopic appendectomy

979 Patients were excluded (convansiyonel appendectomy)

54 Patients were excluded (-22 Patients refused the study -6 Patients convert to open surgery -26 patients underwent other surgival procedures) 41 Patients

20 (48.7%) patients treated with Hem-o-lok clips (Group I)

21 (51.2%) patients treated with intracorporal knotting (Group II)

Included in analysis

Figure 1. Analysis of patients.

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Ureyen et al. Hem-o-lok clips versus intracorporeal knotting for the closure of the appendix stump in laparoscopic appendectomy

Table 1. Demographic and histopathological results

Hem-o-lok Clips

Suture

n % Mean±SD

n %

p

Mean±SD

Gender

Male

15

75

18

85.7

Female

5

25

3

14.3

0.454

Age

38.40±16.36

33.10±11.63

0.361

Body Mass Index

25.90±3.82

25.73±6.25

0.521

American Society of Anesthesiologists

1.75±0.44

1.86±0.48

0.485

Histopathology

Acute appendicitis

15

75

18

85.7

Lymphoid tissue hyperplasia

4

15

2

9.5

Perforated

2

10

1

4.8

0.769

SD: Standard deviation.

Table 2. Operation time, length of the hospital stay and hospital cost according to groups

Hem–o–Clips

Suture p*

Mean±SD Median (Min.–Max.) Mean±SD Median (Min.–Max.)

Operation time (minute) Length of hospital stay (day) Hospital cost ($)

69.00±15.78

65 (45–100)

80.71±23.15

75 (45–120)

0.101

2.00±1.21

2 (1–5)

2.14±1.42

2 (1–6)

0.707

221±60

205 (152–375)

199±70.8

170 (127–385)

0.100

*Mann–Whitney U analysis. SD: Standard deviation; Min.: Minimum; Max.: Maximum.

Table 3. 2–6–12–24–36th hour and 7th day pain scores according to groups

Hem–o–Clips

Suture p*

Ave.±SD

Median (Min.–Max.)

Ave.±SD

Median (Min.–Max.)

2. hour

4.35±2.41

4 (0–8)

3.86±3.04

2 (0–10)

0.355

6. hour

3.4±2.62

4 (0–8)

2.76±2.86

2 (0–8)

0.396

12. hour

2.8±2.69

3 (0–8)

1.9±2.12

1 (0–6)

0.311

24. hour

1.4±1.9

0.5 (0–7)

0.95±1.36

1 (0–5)

0.615

36. hour

0.65±1.81

0 (0–8)

0.33±0.8

0 (0–3)

0.665

7. hour

0.2±0.52

0 (0–2)

0±0

0 (0–0)

0.069

*Mann–Whitney U analysis. Ave: Average; SD: Standard deviation; Min.: Minimum; Max.: Maximum.

statistically significant (p<0.0001). The effects of the operation type on pain scores were not statistically significant (p>0.05) (Fig. 2).

DISCUSSION The method for laparoscopic closure of the appendix stump should be simple, reliable, inexpensive and feasible. Intracorporeal knotting requires more experience but do not require 386

a certain cost as hem-o-lok clips.[16] One of the most feared complications after laparoscopic appendectomy is an intraabdominal abscess. It is argued that the closed stump may open again and lead to the development of abdominal abscess. [12] Soll et al.[12] compared Hem-o-lok clips with endoloop in their series of 813 cases. They found 1% intraabdominal abscess in hem-o-lok gorup and 4% in the endoloop group. There was no intraabdominal abscess in the intracorporeal Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Ureyen et al. Hem-o-lok clips versus intracorporeal knotting for the closure of the appendix stump in laparoscopic appendectomy

Operation type Clips Suture

5

Estimated Marginal Means

4

3

2

1

0 2h

6h

12h

24h

36h

7 day

Time

Figure 2. The relationship between the operation type and 2–6– 12–24–36. hour and 7. day pain scores.

knotting group in a series of 61 patients comparing the intracorporeal knotting with titanium clips.[10] In our study, there was no intraabdominal abscess in both suture and Hem-o-lok clip groups. Concerning complications, there was no significant difference between intracorporeal knotting Hem-o-loc clipsin our study. Our complication rates were similar to the literature.[10,13] In a cohrane analysis for the proper closure method of the appendix stump, it was stated that there is a need for studies with high evidence value between the closure methods. [17] In a meta-analysis of the closure of the appendix stump, intracorporeal knotting was found to be more advantageous in the development of intra-abdominal and wound infection compared to other methods. In this study, it was emphasized that studies about suture ligation should be conducted. [1] In the comparative studies of intracorporeal suture with titanium clips, Ates et al.[10] found that only the duration of surgery was higher in the intracorporeal knotting. There was no prospective randomized study comparing hemoclips with intracorporeal knotting in the literature. To our knowledge, our study is the first study in this respect. In a retrospective series similar to our study conducted by Subasi et al.,[16] there was no difference observed between the two groups about hospital stay, complication and duration of surgery. In different studies, the cost of hemoloc clips was 21 euro[13] and 29 dollars,[9] while the suture cost was about 2 dollars. [18] In our study, the suture cost was about 2 dollars, while the hemoloc clip was about 29 dollars. The total cost for the laparoscopic appendectomy was $199 in the intracorporeal group, and $ 221 in the hemoclips group. Although the cost Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

difference between the two groups is not statistically significant, the closure of the appendiceal stump with intracorporeal knotting may be the primary choice in economically low-income countries. Different studies using intracorporeal knotting reported mean operation time as 79 and 63 minutes.[10,15] The operation time may be longer if the surgeons are not experienced in the suture technique.[15] In the studies evaluating the cases using hemoclips, they found that the mean operation time was 61.5 and 59 minutes.[12,13] Also, hemoclips can be administered without a learning curve or specific experience.[8] In our study, the median operation time was 75 minutes in the suture group and 65 in the hemoclips group. Although there was no significant difference between them, we have attributed the excess time of the suture arm to because we do not use intracorporeal knotting in our daily laparoscopy experience. Many methods have been compared in the studies about the closure of appendix stump. Limited data for cost analysis, failure to determine the exclusion criteria, no observation for the quality of life, postoperative pain scale and recovery time were seen as the limitations of these studies. [1] Our study is important in this respect. There was no difference between the intracorporeal knotting and the Hemo-lok clips about postoperative pain scale and postoperative recovery (postoperative nausea, vomiting, gaita discharge, andoral intake time). The pain scale was similar in both groups. Nearly 36 hours later, the pain was almost completely lost. The limitation of our study was the small number of patients in both groups. Also, as the follow-up period was one month, we have no comments about long term results.

Conclusion Our study showed that either intracorporeal knotting or Hem-o-loc clips were effective, reliable and cost-effective in laparoscopic appendectomy. Because the suture is always accessible, intracorporeal knotting can be used safely by experienced surgeons in the closure of the appendix stump. Ethics Committee Approval: This study is registered retrospectively on the clinicaltrials.gov database and approved by the Ethics Committee of University of Health Sciences, Izmir Bozyaka Training and Research Hospital (decision date: 24.03.2015-no:3). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: O.U., E.İ., E.D.; Design: O.U., E.D., E.İ.; Supervision: E.İ., M.Y., O.U.; Fundings: S.T., E.D., O.U.; Materials: O.U., S.T., E.D.; Data: E.İ., M.Y., O.U.; Analysis: O.U., S.T., M.Y.; Literature search: O.U., E.İ., E.D.; Writing: O.U., S.T., E.D.; Critical revision: E.İ., M.Y., S.T. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. 387


Ureyen et al. Hem-o-lok clips versus intracorporeal knotting for the closure of the appendix stump in laparoscopic appendectomy

REFERENCES 1. Antoniou SA, Mavridis D, Hajibandeh S, Hajibandeh S, Antoniou GA, Gorter R, et al. Optimal stump management in laparoscopic appendectomy: A network meta-analysis by the Minimally Invasive Surgery Synthesis of Interventions and Outcomes Network. Surgery 2017;162:994−1005. 2. Masoomi H, Mills S, Dolich MO, Ketana N, Carmichael JC, Nguyen NT, et al. Does laparoscopic appendectomy impart an advantage over open appendectomy in elderly patients? World J Surg 2012;36:1534−9. 3. Gorter RR, Eker HH, Gorter-Stam MA, Abis GS, Acharya A, Ankersmit M, et al. Diagnosis and management of acute appendicitis. EAES consensus development conference 2015. Surg Endosc 2016;30:4668–90. 4. Di Saverio S, Birindelli A, Kelly MD, Catena F, Weber DG, Sartelli M, et al. WSES Jerusalem guidelines for diagnosis and treatment of acute appendicitis. World J Emerg Surg 2016;11:34. 5. Gomes CA, Junior CS, de Peixoto RO, Netto JM, Gomes CC, Gomes FC. Appendiceal stump closure by metal endoclip in the management of complicated acute appendicitis. World J Emerg Surg 2013;8:35. 6. Beldi G, Vorburger SA, Bruegger LE, Kocher T, Inderbitzin D, Candinas D. Analysis of stapling versus endoloops in appendiceal stump closure. Br J Surg 2006;93:1390–3. 7. Khanna S, Khurana S, Vij S. No clip, no ligature laparoscopic appendectomy. Surg Laparosc Endosc Percutan Tech 2004;14:201–3. 8. Hue CS, Kim JS, Kim KH, Nam SH, Kim KW. The usefulness and safety of Hem-o-lok clips for the closure of appendicular stump during laparoscopic appendectomy. J Korean Surg Soc 2013;84:27–32. 9. Reinke CE, Tabone LE, Fong P, Yoo JS, Park CW. Safety and Efficacy of Polymeric Clips for Appendiceal Stump Closure. JSLS 2016;20:e2016.00045. 10. Ates M, Dirican A, Ince V, Ara C, Isik B, Yilmaz S. Comparison of intracorporeal knot-tying suture (polyglactin) and titanium endoclips in

laparoscopic appendiceal stump closure: a prospective randomized study. Surg Laparosc Endosc Percutan Tech 2012;22:226–31. 11. Partecke LI, Kessler W, Diedrich S, von Bernstorff W, Heidecke CD, Patrzyk M. Disease-adapted closure of the appendicular stump in laparoscopic appendectomy. [Article in German]. Zentralbl Chir 2013;138:262–9. 12. Soll C, Wyss P, Gelpke H, Raptis DA, Breitenstein S. Appendiceal stump closure using polymeric clips reduces intra-abdominal abscesses. Langenbecks Arch Surg 2016;401:661–6. 13. Wilson M, Maniam P, Ibrahim A, Makaram N, Knight SR, Patil P. Polymeric clips are a quicker and cheaper alternative to endoscopic ligatures for securing the appendiceal stump during laparoscopic appendicectomy. Ann R Coll Surg Engl 2018;100:454–8. 14. Shaikh FM, Bajwa R, McDonnell CO. Management of appendiceal stump in laparoscopic appendectomy-clips or ligature: a systematic review and meta-analysis. J Laparoendosc Adv Surg Tech A 2015;25:21–7. 15. Kiudelis M, Ignatavicius P, Zviniene K, Grizas S. Analysis of intracorporeal knotting with invaginating suture versus endoloops in appendiceal stump closure. Wideochir Inne Tech Maloinwazyjne 2013;8:69–73. 16. Subasi O, Coskun M, Yuksel A, Yildiz SY, Turgut HT, Gunes A. Comparison of the methods of intracorporeal knot and hem-o-lok clip to cover the stumps in laparoscopic appendectomy (pp. 598-600). Annals Med Res 2018;25:598−600. 17. Mannu GS, Sudul MK, Bettencourt-Silva JH, Cumber E, Li F, Clark AB, Loke YK. Closure methods of the appendix stump for complications during laparoscopic appendectomy. Cochrane Database Syst Rev 2017;11:CD006437. 18. Gonenc M, Gemici E, Kalayci MU, Karabulut M, Turhan AN, Alis H. Intracorporeal knotting versus metal endoclip application for the closure of the appendiceal stump during laparoscopic appendectomy in uncomplicated appendicitis. J Laparoendosc Adv Surg Tech A 2012;22:231–5.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Laparaskopik apendektomide apendiks güdüğünün kapatılmasında intrakorporial sütüre karşı Hem-o-lok clips: Randomize ileriye yönelik çalışma Dr. Orhan Üreyen, Dr. Sedat Tan, Dr. Emrah Dadalı, Dr. Mehmet Yıldırım, Dr. Enver İlhan Sağlık Bilimleri Üniversitesi, İzmir Bozyaka Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İzmir

AMAÇ: İntrakorporial sütür ve Hem-o-lok klipsin birbirlerine etkinlik, güvenilirlik ve maliyet açısından üstünlüklerinin araştırılması amaçlandı. GEREÇ VE YÖNTEM: Acil servise başvuran ve akut apandist tanısı ile ameliyat kararı verilen olgulara laparoskopik apendektomi uygulandı. Apendiks güdüğü Hem-o-lok klips (Grup I) ve intrakorporial sütür 2/0 ipek (Grup II) ile kapatıldı. Gruplar demografik veriler (yaş cinsiyet, vücut kitle indeksi [VKİ], ASA), operasyon süresi, maliyet, operasyondan sonra 2.–6.–12.–24.–36. saat ve 7. gün ağrı yönünden karşılaştırıldı. BULGULAR: Olguların yaş, cinsiyet ve VKİ gibi demografik verileri gruplar arası benzerdi (p>0.05). Peroperatif ve ameliyat sonrası görülen komplikasyonlar açısından gruplar arası karşılaştırmalarında anlamlı fark bulunmadı (p>0.05). Hiçbir olguda ameliyat sonrası bulantı kusma, ileus ve karıniçi apse görülmedi. Olguların ameliyat süreleri, hastanede kalış süreleri ve maliyeti açısından gruplar arasında anlamlı fark bulunmadı (p>0.05). Olguların gruplara göre ağrı skorları arasında anlamlı fark bulunmadı. Ameliyat tipi ağrı skorlarını etkilemedi (p>0.05). TARTIŞMA: Bu çalışma laparoskopi apendektomi de, apendiks güdüğünün kapatılmasında hem intrakorporial sütür hemde Hem-o-lok klipsin etkin, güvenilir ve benzer maliyetli olduğunu gösterdi. Uygulanacak yöntemin seçiminde cerrahın deneyimi baz alınmalıdır. Anahtar sözcükler: Apandisit; laparaskopik cerrahi; maliyet etkinliği. Ulus Travma Acil Cerrahi Derg 2020;26(3):384-388

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ORIGIN A L A R T IC L E

Comparison of thiol/disulphide homeostasis with modified Alvarado and RIPASA scores in the diagnosis of acute appendicitis Servan Gökhan, M.D.,1 İsmail Erkan Aydın, M.D.,2 Gül Pamukçu Günaydın, M.D.,1 Çağdaş Yıldırım, M.D.,1 Fatih Tanrıverdi, M.D.,1 Selahattin Gürü, M.D.,3 Fatih Ahmet Kahraman, M.D.,1 Özcan Erel, M.D.4 1

Department of Emergency Medicine, Yıldırım Beyazıt University Faculty of Medicine, Ankara-Turkey

2

Department of Emergency Medicine, Çankırı State Hospital, Çankırı-Turkey

3

Department of Emergency Medicine, Bilkent City Hospital, Ankara-Turkey

4

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

ABSTRACT BACKGROUND: This study aims to investigate the role of thiol/disulfide homeostasis parameters in the diagnosis of acute appendicitis and to determine whether it is beneficial to use these parameters in combination with the modified Alvarado and RIPASA scoring systems. METHODS: This study was prospectively carried out on 265 patients who presented to the emergency department with the complaint of right lower quadrant pain between 01.07.2017 and 31.12.2017, and met the inclusion criteria of this study. Oxidative stress markers were evaluated on two groups. The relationship between these parameters and the modified Alvarado and RIPASA scoring systems was analyzed. RESULTS: The mean levels of disulfide, disulfide/native thiol and disulfide/total thiol were found to be significantly higher in the appendicitis group (p<0.001). The mean levels of native thiol, total thiol and native thiol/total thiol were significantly lower in the same group (p<0.001, 0.001 and 0.007, respectively). The mean levels of disulfide, disulfide/native thiol and disulfide/total thiol were recorded to be significantly higher in the high-risk group according to the results of RIPASA (p=0.016, 0.003 and 0.001, respectively). CONCLUSION: Thiol/disulfide homeostasis parameters can be used with the modified Alvarado and RIPASA scoring systems in the diagnosis of acute appendicitis. Keywords: Acute appendicitis; modified Alvarado and RIPASA; thiol/disulfide homeostasis.

INTRODUCTION Acute appendicitis is the most common cause in abdominal pain cases presenting to the emergency department and requiring urgent surgical interventions. Acute appendicitis is a medical emergency that may progress to a series of complications, such as peritonitis, or even result in death unless it is treated.[1,2] The incidence of acute appendicitis is approximately 6–8% in both western and eastern societies for a

life-long period.[3–5] Although it is seen only in approximately 10% of the general population, there are certain diagnostic difficulties, and the negative appendectomy rates may exceed 15–20% in many centers.[6,7] Acute appendicitis is an acute inflammatory condition of the appendiceal tissues that is characterized by the increased mucosal barrier permeability and luminal obstruction.[8] Microscopic changes in acute appendicitis may vary from minimal focal inflammation to total wall necrosis.[9]

Cite this article as: Gökhan S, Aydın İE, Pamukçu Günaydın G, Yıldırım Ç, Tanrıverdi F, Gürü S, et al. Comparison of thiol/disulphide homeostasis with modified Alvarado and RIPASA scores in the diagnosis of acute appendicitis. Ulus Travma Acil Cerrahi Derg 2020;26:389-395. Address for correspondence: İsmail Erkan Aydın, M.D. Çankırı Devlet Hastanesi, Acil Servis Kliniği, Çankırı, Turkey Tel: +90 376 - 213 27 27 E-mail: erkanaydinmd@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):389-395 DOI: 10.14744/tjtes.2019.65118 Submitted: 31.05.2019 Accepted: 27.12.2019 Online: 13.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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The diagnosis of acute appendicitis may be delayed, and complications may occur despite physical examination, laboratory tests and imaging methods.[10,11] Due to the presence of atypical symptoms, there is a confusion of appendicitis with urogenital diseases and its similarity with gynecological diseases in the elderly population, children, pregnant women and female patients.[1,12] For these reasons, the researchers have worked on new parameters, including oxidative stress markers, to diagnose the afore-said disease more clearly, and they have improved the diagnostic scoring systems. Although the pathophysiology of acute appendicitis is generally known, the factors playing a role in its development are still being investigated. The probable role of some oxidative stress markers in the development of inflammation and the occurrence and diagnosis of acute appendicitis has been investigated in various studies.[9,13,14] Thiol/disulfide homeostasis has a significant place in antioxidant protection, signal transduction and detoxification in addition to the maintenance of enzyme activities and transcriptional factors and apoptosis. [15,16] Disruptions are seen in these vital cellular functions in the process of abnormal thiol/disulfide homeostasis. Pathologies are observed in organelles because of the oxidative stress, which results in imbalances.[15] It has been indicated in the literature that the disruption of thiol/disulfide homeostasis plays a significant role in the inflammation-causing the diseases.[17,18] The Modified Alvarado and RIPASA (The Raja Isteri Pengiran Anak Saleha Appendicitis) scorings (Table 1 and Table 2) are two important scoring systems used for the diagnosis of acute appendicitis, and these scoring systems are utilized for ensuring a rapid and accurate diagnosis.[1,6] In this study, we aimed to investigate the role of thiol/disulfide homeostasis parameters, a current oxidative stress marker, in the diagnosis of acute appendicitis and the impacts of the relationship between the oxidative stress and two important scoring systems on the development and diagnosis of acute appendicitis. Table 1. Modified Alvarado scale[19] Manifestations Value Symptoms

Migration of pain

1

Anorexia

1

1

Nausea and/or vomiting

Signs

Right Lower Quadrant tenderness

2

Rebound

1

1

Elevated temperature

Laboratory values Leukocytosis

390

2

Table 2. RIPASA score[19] Parameters Score Female 0.5 Male 1.0 Age >40 years

0.5

Age <39.9 years

1.0

Right iliac fossa pain

0.5

Migration of pain to right iliac fossa

0.5

Anorexia 1.0 Nausea and vomiting

1.0

Duration of symptoms <48 hours

1.0

Duration of symptoms >48 hours

0.5

Right iliac fossa tenderness

1.0

Guarding

2.0

Rebound tenderness

1.0

Rovsing’s sign

2.0

Fever 1.0 Raised white blood cell

1.0

Negative urine analysis

1.0

Total score

16.5

RIPASA: The Raja Isteri Pengiran Anak Saleha Appendicitis.

MATERIALS AND METHODS Study Design and Participants The approval was obtained from the Ethics Committee of the Faculty of Medicine at Ankara Yıldırım Beyazıt University in accordance with the latest version of the Declaration of Helsinki. A prospective study was carried out on 265 patients who were admitted to the Emergency Department of Atatürk Training and Research Hospital affiliated to the Faculty of Medicine at Ankara Yıldırım Beyazıt University with the complaint of right lower quadrant pain between 01.07.2017 and 31.12.2017, and they were followed up with the pre-diagnosis of acute appendicitis. Out of 265 patients, 97 were diagnosed with acute appendicitis (Group 1), and the remaining 168 patients were classified as the group without appendicitis (Group 2). Acute appendicitis was diagnosed using laboratory tests and imaging methods, such as ultrasonography and computed tomography, as well as the clinical symptoms and physical examination. Standard study forms were filled with necessary information about the patients taking part in this study, such as their age, sex, complaints, medical history, concomitant system findings and diseases, signs and symptoms at the moment of admission to the emergency department (abdominal tenderness-rebound-defense, nausea-vomiting, high fever, loss of appetite, and location and dissemination of the pain), laboratory findings, imaging results, operation notes about the Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


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patients undergoing a surgical procedure, and histopathology results. The patients having a chronic disease, the individuals using any substance or drug, the ones suffering from any serious trauma in the recent year and undergoing appendectomy procedure before, pregnant women and the patients under the age of 18 were excluded from this study.

Biochemical Analysis We asked the participants to give venous blood samples for the measurement of thiol/disulfide homeostasis parameters. Then, we centrifuged the blood samples of the patients at 1500 rpm for ten minutes, and we separated the plasma and serum samples. We stored the serum samples at -80°C until the collection of all samples. In the following phase, we sent the plasma samples that were analyzed concerning thiol/disulfide levels to the biochemical laboratory at Atatürk Training and Research Hospital, Ankara, Turkey, subsequent to the completion of the sample collection process. The levels of thiol/disulfide homeostasis have been measured using a one-sided test since 1979;[20] however, the new method developed by Erel and Neşelioğlu has enabled the separate and collective measurement of both variables.[15] The laboratory staff measured the native thiol and total thiol using a new and fully automatic system, and they calculated the ratios of disulfide, disulfide/native thiol, disulfide/total thiol and native thiol/total thiol (ErelNeselioglu).[15] A novel automated method with an automated analyzer was used for the performance of serum thiol-disulfide profile tests (Cobas 501, Roche, Mannheim, Germany). The personal information of the laboratory staff carrying out the measurement analysis on the plasma thiol/disulfide homeostasis was kept confidential, and it was not indicated in the patients’ clinical information and outcome. The treating physicians, study staff, or investigators were not informed about the results during the study period.

Scoring Systems Modified Alvarado scores of the patients (Table 1) were calculated, and the patients were classified as the high-risk group for 7 or higher scores and the low-risk group for the scores below 7.[21,22] At the same time, the Ripasa scores of the patients (Table 2) were calculated, and the patients were classified as the high-risk group for 7.5 or higher scores and the low-risk group for the scores below 7.5.[22,23] Thiol, disulfide, disulfide/native thiol, disulfide/total thiol and native thiol/total thiol values were evaluated both in group 1 and group 2 and in the high-risk group and the low-risk group determined through the Modified Alvarado and Ripasa scores.

Statistical Analysis The results were given as mean±SD. Univariate statistical analyses were performed using the chi-square test for categorical variables and student’s t-test for continuous variables. P<0.05 was accepted to be statistically significant.

RESULTS

Out of 265 patients included in this study, 60.8% were male (n=161), and 39.2% were female (n=104). The mean age of the patients was 32.45±12.19 years. Male population in Group 1 was 74.2% (n=72) and female population was 25.8% (n=25). The mean age of the patients was 32.84±12.75 years. 53% of Group 2 was represented by the male population (n=89) and this percentage was 47% for female patients (n=79), and the mean age of the patients in this group was 32.23±11.89 years. There was no statistically significant difference between group 1 and group 2 concerning age; however, the higher number of the male patients in group 1 was found to be significant (p=0.702, p=0.001, respectively). When group 1 was compared with group 2 according to the Thiol/Disulfide homeostasis parameters, the mean values of disulfide, disulfide/native thiol and disulfide/total thiol were

Table 3. Comparison of the Group 1 and Group 2 in concerning Thiol/Disulfide homeostasis parameters, Ripasa and Modified Alvarado scorings

Group 1 (n=97)

Group 2 (n=168)

p

Mean±SD Mean±SD

Native thiol (µmol/L)

411.89±89.18

449.29±61.47

Total thiol (µmol/L)

<0.001

464.12 ±81.01

495.49±64.46

0.001

Disulfide (µmol/L)

29.11±15.32

22.08±10.50

<0.001

Disulfide/native thiol

0.082±0.078

0.050±0.026

<0.001

Disulfide/total thiol

0.065±0.040

0.045±0.022

<0.001

Native thiol/total thiol

0.878±0.092

0.907±0.062

0.007

RIPASA score

10.02±2.36

6.93±1.71

<0.001

Modified Alvarado score

6.28±1.40

4.18±1.56

<0.001

RIPASA: The Raja Isteri Pengiran Anak Saleha Appendicitis; SD: Standard deviation.

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determined to be significantly higher in group 1 (p<0.001), and the mean values of native thiol, total thiol and native thiol/ total thiol were found to be significantly lower in the same group (p<0.001, 0.001 and 0.007, respectively). Thiol/Disulfide homeostasis parameters of both groups are given in Table 3. When the high-risk group and the low-risk group determined using Ripasa scoring were compared to each other in accordance with Thiol/Disulfide homeostasis parameters, the mean values of disulfide, disulfide/native thiol and disulfide/ total thiol were found to be significantly higher in the highrisk group (p=0.016, 0.003 and 0.001, respectively) while the mean values of native thiol and total thiol were detected to be significantly lower in the same group (p=0.006 and 0.003, respectively). There was no significant difference between the groups concerning native thiol/total thiol ratios (p=0.386). Thiol/Disulfide homeostasis parameters of the high-risk group and the low-risk group determined through Ripasa scoring are given in Table 4. When the high-risk group and the low-risk group determined through the modified Alvarado scoring were compared to each other according to Thiol/Disulfide homeostasis parameters, it was found out that the mean values of native thiol and total

thiol were significantly higher in the low-risk group (p=0.043 and 0.039, respectively). On the other hand, no significant difference was recorded between two groups concerning the mean values of disulfide, disulfide/native thiol, disulfide/ total thiol and native thiol/total thiol. Table 5 shows the Thiol/ Disulfide homeostasis parameters of the high risk and low-risk groups according to the modified Alvarado scoring.

DISCUSSION Acute appendicitis is the most common cause of abdominal pain requiring surgical intervention worldwide, and it is a surgical pathology associated with inflammatory responses. [8,24] Clinic history and physical examination are the most important points in the diagnosis of acute appendicitis. On the other hand, numerous methods including laboratory tests, ultrasonography and computed tomography, are used to diagnose acute appendicitis correctly.[25,26] Despite all these techniques, the rate of misdiagnosis is considerably high. For these reasons, the correct diagnosis of acute appendicitis is regarded as a considerable challenge for physicians in today’s world. The development of specific tests for the diagnosis of acute appendicitis and the use of scoring systems, such as the Modified Alvarado and RIPASA, will not only prevent unnecessary surgical interventions but also result in a decrease

Table 4. Comparison of thiol/disulfide homeostasis parameters according to RIPASA scoring

High risk (n=144)

Low risk (n=121)

p

Mean±SD Mean±SD

Native thiol (µmol/L)

424.18±79.45

449.18±66.88

0.006

Total thiol (µmol/L)

471.99±73.33

498.32±68.92

0.003

Disulfide (µmol/L)

26.36±14.13

22.62±11.01

0.016

Disulfide/native thiol

0.070±0.067

0.051±0.027

0.003

Disulfide/total thiol

0.058±0.036

0.046±0.023

0.001

Native thiol/total thiol

0.893±0.091

0.901±0.052

0.386

RIPASA: The Raja Isteri Pengiran Anak Saleha Appendicitis; SD: Standard deviation.

Table 5. Comparison of thiol/disulfide homeostasis parameters according to the modified Alvarado scoring

High risk (n=58)

Low risk (n=207)

p

Mean±SD Mean±SD

Native thiol (µmol/L)

417.15±78.62

440.77±73.17

0.043

Total thiol (µmol/L)

465.85±75.58

489.10±70.86

0.039

Disulfide (µmol/L)

26.58±13.58

24.11±12.70

0.219

Disulfide/native thiol

0.069±0.053

0.059±0.053

0.214

Disulfide/total thiol

0.059±0.037

0.050±0.029

0.112

Native thiol/total thiol

0.893±0.087

0.898±0.072

0.703

SD: Standard deviation.

392

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in morbidity and mortality due to the possibility of early diagnosis.[14,21] Recently, the researchers have studied on many markers, such as oxidative stress markers and inflammatory markers, primarily to improve the diagnosis of acute appendicitis.[8,13,27–29] Our study has indicated higher incidence rate of acute appendicitis in male patients in conformity with the literature. [30,31] In our study, the number of male patients was recorded to be higher than the women’s number both in the general patient population included in this study and in the group suffering from acute appendicitis. At the same time, the number of males was higher than females in the group with acute appendicitis. This medical condition is mostly observed in young adults, and the peak incidence of the disease is especially recorded in the second and third decades.[32] While there was no significant relationship between the sex and age of our patients, the age range was found to be compatible with the literature.[31,33] Yildirim et al.[34] reported in their study on the verification of the diagnosis of acute appendicitis that the inflammatory markers were elevated and that they could be used in the process. In another study carried out by Ozan et al.,[35] the inflammation markers were seen to increase in acute appendicitis. Yilmaz et al.[36] stated that oxidative stress showed an increase in acute appendicitis. Dumlu et al.[9] performed a study on the oxidative stress markers, including serum and total thiol levels in the tissues in acute appendicitis by analyzing the serum and tissue samples, and they demonstrated that the afore-said levels were different in the patients with acute appendicitis when compared to the control group. In the results of the same study, Dumlu et al.[9] remarked that the balance between oxidant and antioxidant defense systems may influence the pathogenesis of acute appendicitis and that the changes on the levels of oxidative stress markers may also play a role in acute appendicitis. It has been indicated in the literature that an increase in disulfide levels and a decrease in thiol levels are expected in the event of oxidative stress.[14,15,37] Dumlu et al.[9] reported in their study that total thiol levels were lower in the group with acute appendicitis than the control group. Similar to the study carried out by Dumlu et al., Yilmaz et al.[36] also found out that the thiol levels showed a decrease in the cases of acute appendicitis. In another study in which thiol/disulfide homeostasis was measured through a new method developed by Erel and Neselioglu,[15] Ozyazici et al.[14] showed that native thiol, total thiol and native thiol/total thiol levels were significantly lower in the patient group with acute appendicitis when compared to the control group and that the disulfide, disulfide/native thiol and disulfide/total thiol levels were higher in the same group. In the study performed by Elmas et al.,[38] disulfide levels and disulfide/native thiol and disulfide/total thiol ratios were found to be higher in the patients with acute appendicitis while native thiol, total thiol and native thiol/total thiol levels were lower in the same group. Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

In our study, disulfide levels and disulfide/native thiol and disulfide/total thiol ratios were measured to be higher in the group with acute appendicitis, which was compatible with the studies in the literature. Also, other infectious and inflammatory conditions may impair thiol-disulphide homeostasis. Disulfide/native thiol and disulfide/total thiol ratios are high at these conditions.[39–41] Similarly, native thiol and total thiol levels as well as native thiol/total thiol ratio were found to be lower in the group with acute appendicitis. In the light of the results obtained from both our research and previous studies, it can be said that the oxidative stress and the impairment of the balance between oxidant and antioxidant systems may play a role in the pathogenesis of acute appendicitis. The Alvarado and Modified Alvarado scoring systems, which are popularly used for the diagnosis of acute appendicitis, have effective sensitivity and specificity, especially for western societies.[42,43] The RIPASA scoring has recently emerged as an important scoring system with more sensitivity, specificity and diagnostic accuracy than the Alvarado scoring system, especially for Asian populations.[1,22] In our study, both the Alvarado and the RIPASA scores were found to be higher in the group with acute appendicitis, which is compatible with the studies in the literature.[19] There are a limited number of studies in the literature showing the relationship between the scoring systems and inflammatory markers in the diagnosis of acute appendicitis.[44–46] In the study carried out by Zouari et al.,[47] it was indicated that there was no difference between the single-use of Alvarado score and the combined utilization of Alvarado and CRP concerning predictive values in the diagnosis of acute appendicitis. Jung et al.[44] reported in their study that Appendicitis Inflammatory Response (AIR) score did not create a significant difference in the distinction between perforated and non-perforated appendicitis in elderly patients, but that the modified AIR score obtained through the combination with Neutrophile-to lymphocyte count ratio may be significant for making a distinction between perforated and non-perforated acute appendicitis risks in elderly patients. According to our literature review, to our knowledge, there is no study showing the correlation between thiol/disulfide homeostasis and the RIPASA and Modified Alvarado scores used in the diagnosis of acute appendicitis. In our study, the mean values of disulfide, disulfide/native thiol and disulfide/ total thiol were found to be higher in the patients with a high risk of acute appendicitis according to RIPASA score, while the mean values of native thiol and total thiol were calculated to be lower in the same group. In accordance with the modified Alvarado score, the mean values of native thiol and total thiol were found to be higher in the low-risk group. On the other hand, no difference was recorded between two groups concerning the mean values of disulfide, disulfide/native thiol, disulfide/total thiol and native thiol/total thiol. High values of disulfide, disulfide/native thiol, and disulfide/total thiol in the 393


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high-risk group determined through RIPASA scoring in the case of acute appendicitis are one of the most outstanding results of our study, and we think that the combined use of the above-mentioned methods may be beneficial for the diagnosis of acute appendicitis. Similarly, we also believe that the detection of high mean values of native thiol and total thiol in the patients with low risk, according to Alvarado scoring, would be useful concerning the follow-up and discharge process of the patients. To our knowledge, our research is the first study in the literature that has analyzed the scoring systems and thiol/ disulfide homeostasis parameters that are oxidative stress markers and comparing these two components in the diagnosis of acute appendicitis. The measurement of thiol/disulfide homeostasis parameters, which are readily available and cheap oxidative stress indicators, can be used as an effective biochemical marker in acute appendicitis. Consequently, the combined use of thiol/disulfide homeostasis parameters and RIPASA and modified scoring systems may facilitate the diagnosis of acute appendicitis. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: S.G., İ.E.A., G.P.G.; Design: S.G., İ.E.A., G.P.G.; Supervision: S.G., F.T., Ö.E.; Fundings: S.G., İ.E.A., Ö.E.; Materials: Ç.Y., F.T., S.G.; Data: İ.E.A., S.G., F.A.K.; Analysis: S.G., G.P.G., Ö.E.; Literature search: İ.E.A., G.P.G., Ç.Y.; Writing: S.G., G.P.G., Ç.Y.; Critical revision: S.G., F.T., F.A.K., Ö.E. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Chong CF, Adi MI, Thien A, Suyoi A, Mackie AJ, Tin AS, et al. Development of the RIPASA score: a new appendicitis scoring system for the diagnosis of acute appendicitis. Singapore Med J 2010;51:220−5. 2. Quick CRG, Reed JB, Harper SJ, Saeb-Parsy K. Essential surgery: Problems, diagnosis and management: With student consult Online Access. Lincoln, UK: Churchill Livingstone; 2013. 3. Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol 1990;132:910–25. 4. Nshuti R, Kruger D, Luvhengo TE. Clinical presentation of acute appendicitis in adults at the Chris Hani Baragwanath academic hospital. Int J Emerg Med 2014;7:12. 5. Memon ZA, Irfan S, Fatima K, Iqbal MS, Sami W. Acute appendicitis: diagnostic accuracy of Alvarado scoring system. Asian J Surg 2013;36:144–9. 6. Kalan M, Talbot D, Cunliffe WJ, Rich AJ. Evaluation of the modified Alvarado score in the diagnosis of acute appendicitis: a prospective study. Ann R Coll Surg Engl 1994;76:418–9. 7. Rao PM, Rhea JT, Novelline RA. Helical CT of appendicitis and diverti-

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Gökhan et al. Comparison of thiol/disulphide homeostasis with modified Alvarado and RIPASA scores in the diagnosis of acute appendicitis racy of plasma markers for early diagnosis in patients suspected for acute appendicitis. Academic Emergency Medicine 2013;20:703−10. 28. Kaya M, Boleken ME, Kanmaz T, Erel O, Yucesan S. Total antioxidant capacity in children with acute appendicitis. Eur J Pediatr Surg 2006;16:34–8. 29. Satomi A, Hashimoto T, Murakami S, Murai H, Kawase H, Takahashi S, et al.. Tissue superoxide dismutase (SOD) activity and immunohistochemical staining in acute appendicitis: correlation with degree of inflammation. J Gastroenterol 1996;31:639−45. 30. Sato Y, Kojimahara N, Kiyohara K, Endo M, Yamaguchi N; Appendicitis study group of Mobi-kids Japan. Association between climatic elements and acute appendicitis in Japan. J Surg Res 2017;211:64–9. 31. Kartal K, Yazıcı P, Ünlü TM, Uludağ M, Mihmanlı M. How to avoid negative appendectomies: Can US achieve this?. Ulus Travma Acil Cerrahi Derg 2017;23:134–8. 32. Rybkin AV, Thoeni RF. Current concepts in imaging of appendicitis. Radiol Clin North Am 2007;45:411–vii. 33. Hobeika C, Hor T, Chereau N, Laforest A, Bachmann R, Sourouille I, et al. Day Surgery for Acute Appendicitis in Adults: A Prospective Series of 102 Patients. Surg Laparosc Endosc Percutan Tech 2017;27:158−62. 34. Yildirim O, Solak C, Koçer B, Unal B, Karabeyoğlu M, Bozkurt B, et al. The role of serum inflammatory markers in acute appendicitis and their success in preventing negative laparotomy. J Invest Surg 2006;19:345−52. 35. Ozan E, Ataç GK, Alişar K, Alhan A. Role of inflammatory markers in decreasing negative appendectomy rate: A study based on computed tomography findings. Ulus Travma Acil Cerrahi Derg 2017;23:477–82. 36. Yilmaz FM, Yilmaz G, Erol MF, Köklü S, Yücel D. Nitric oxide, lipid peroxidation and total thiol levels in acute appendicitis. J Clin Lab Anal 2010;24:63–6. 37. Kundi H, Gok M, Cetin M, Kiziltunç E, Topcuoglu C, Neselioglu S, et.al. Association of thiol disulfide homeostasis with slow coronary flow. Scandinavian Cardiovascular J 2016;50:213–7.

38. Elmas B, Yildiz T, Yazar H, İlçe Z, Bal C, Özbek B, et.al. New Oxidative Stress Markers Useful in the Diagnosis of Acute Appendicitis in Children: Thiol/Disulfide Homeostasis and the Asymmetric Dimethylarginine Level. Pediatr Emerg Care 2017 Nov 14. doi: 10.1097/ PEC.0000000000001339. [Epub ahead of print] 39. Şimşek E, Bicer CK, Mazlumoğlu MR, Kara SS, Erel O, Çarlıoğlu A. Is otitis media with effusion associated with oxidative stress? Evaluation of thiol/disulfide homeostasis. Am J Otolaryngol 2019;40:164–7. 40. Tuzcu A, Baykara RA, Omma A, Acet GK, Dogan E, Cure MC, et al. Thiol/Disulfide homeostasis in patients with rheumatoid arthritis. Rom J Intern Med 2019;57:30−6. 41. 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. 42. Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med 1986;15:557–64. 43. Owen TD, Williams H, Stiff G, Jenkinson LR, Rees BI. Evaluation of the Alvarado score in acute appendicitis. J R Soc Med 1992;85:87–8. 44. Jung SK, Rhee DY, Lee WJ, Woo SH, Seol SH, Kim DH, et al. Neutrophil-to-lymphocyte count ratio is associated with perforated appendicitis in elderly patients of emergency department. Aging Clin Exp Res 2017;29:529−36. 45. Andersson M, Andersson RE. The appendicitis inflammatory response score: a tool for the diagnosis of acute appendicitis that outperforms the Alvarado score . World J Surg 2008;32:1843–9. 46. Khanafer I, Martin DA, Mitra TP, Eccles R, Brindle ME, Nettel-Aguirre A, et al. Test characteristics of common appendicitis scores with and without laboratory investigations: a prospective observational study. BMC Pediatr 2016;16:147. 47. Zouari M, Jallouli M, Louati H, Kchaou R, Chtourou R, Kotti A, et al. Predictive value of C-reactive protein, ultrasound and Alvarado score in acute appendicitis: a prospective pediatric cohort. Am J Emerg Med 2016;34:189−92.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut apandisit tanısında tiyol/disülfit homeostazının modifiye Alvarado ve RIPASA skorları ile karşılaştırılması Dr. Servan Gökhan,1 Dr. İsmail Erkan Aydın,2 Dr. Gül Pamukçu Günaydın,1 Dr. Çağdaş Yıldırım,1 Dr. Fatih Tanrıverdi,1 Dr. Selahattin Gürü,3 Dr. Fatih Ahmet Kahraman,1 Dr. Özcan Erel4 Yıldırım Beyazıt Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Ankara Çankırı Devlet Hastanesi, Acil Servis Kliniği, Çankırı 3 Bilkent Şehir Hastanesi, Acil Servis Kliniği, Ankara 4 Yıldırım Beyazıt Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Ankara 1 2

AMAÇ: Bu çalışma, akut apandisit tanısında tiyol/disülfit homeostaz parametrelerinin rolünü göstermeyi ve bu parametrelerin modifiye Alvarado ve RIPASA skorlama sistemleriyle birlikte kullanılmasının yararlı olup olmadığını belirlemeyi amaçlamaktadır. GEREÇ VE YÖNTEM: Bu çalışma, acil servise 01.07.2017 ve 31.12.2017 tarihleri arasında sağ alt kadran ağrısı şikayeti ile başvuran ve çalışmanın dahil edilme kriterlerini karşılayan 265 hastada ileriye yönelik olarak gerçekleştirildi. Oksidatif stres belirteçleri iki grupta değerlendirildi. Bu parametrelerle modifiye Alvarado ve The Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) skorlama sistemleri arasındaki ilişki analiz edildi. BULGULAR: Apandisit grubunda ortalama disülfit, disülfit/native tiyol ve disülfit/total tiyol seviyeleri anlamlı olarak yüksek bulundu (p<0.001). Native tiyol, total tiyol ve native tiyol/total tiyol ortalamaları aynı grupta anlamlı olarak düşüktü (sırasıyla, p<0.001, 0.001 ve 0.007). Ortalama disülfid, disülfid/native tiyol ve disülfid/total tiyol seviyelerinin RIPASA sonuçlarına göre yüksek riskli grupta anlamlı olarak yüksek olduğu saptanmıştır (sırasıyla, p=0.016, 0.003 ve 0.001). TARTIŞMA: Tiyol/disülfit homeostaz parametreleri, akut apandisit tanısında modifiye Alvarado ve RIPASA skorlama sistemleriyle birlikte kullanılabilir. Anahtar sözcükler: Akut apandisit; modifiye Alvarado ve RIPASA; tiyol/disülfit homeostazı. Ulus Travma Acil Cerrahi Derg 2020;26(3):389-395

doi: 10.14744/tjtes.2019.65118

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ORIGIN A L A R T IC L E

Perioperative outcomes of the patients treated using laparoscopic cholecystectomy after emergent endoscopic retrograde cholangiopancreatography for bile duct stones: Does timing matter? Rahman Şenocak, M.D., Süleyman Utku Çelik, M.D., Şahin Kaymak, M.D., Oğuz Hançerlioğulları, M.D. Department of General Surgery, University of Health Sciences Gülhane Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: There is no consensus on the optimal timing for laparoscopic cholecystectomy (LC) after emergent endoscopic retrograde cholangiopancreatography (ERCP) for suspected choledocholithiasis. Although certain data suggest that an early interval or single-stage treatment by LC, together with laparoscopic bile duct exploration, has more favorable outcomes, delayed LC is most often preferred as the standard treatment of patients with gallstones and choledocholithiasis following ERCP due to lack of experience, necessary instrumentation, or organizational restrictions. This study aims to compare the effects of different time intervals between ERCP and LC on perioperative outcomes. METHODS: In this paper, preoperative and postoperative data from consecutive patients who were treated for common bile duct stones with emergent ERCP and then underwent LC were reviewed retrospectively. To evaluate the impacts of different time intervals on outcomes, patients were classified into three groups according to the duration from the last ERCP to LC: within two weeks (Group 1), between 2–6 weeks (Group 2), and over six weeks (Group 3). RESULTS: This study involved an analysis of 67 patients with a mean age of 52.8 years. Overall conversion rate was 20.0% in Group 1, 25.0% in Group 2, and 13.6% in Group 3 (p=0.646). The rate of conversion to open surgery was 25.0% in male patients and 14.2% in females. In addition, no significant difference was found between the groups concerning gender, comorbidities, laboratory and gallbladder features, operation time, and length of the hospital stay. The perioperative complication rate was found to be 17.9%; however, there was no significant difference between the three groups. CONCLUSION: Our results support that LC after ERCP is more complex and has higher conversion rates than LC for uncomplicated cholelithiasis. Although no significant effect of different time intervals between ERCP and LC on perioperative outcomes was demonstrated in patients with common bile duct stones concomitant with cholelithiasis, the 2–6 weeks after ERCP is a critical period for conversion to open surgery. It is recommended that LC after ERCP should be performed in the early period, considering that serious complications may occur in the late period and recurrent biliary attacks may occur. Keywords: Choledocholithiasis; cholelithiasis; complication; endoscopic retrograde cholangiopancreatography; laparoscopic cholecystectomy.

INTRODUCTION Approximately 15% of the patients with cholelithiasis have

simultaneous bile duct stones, whereas 95% of the patients with bile duct stones have cholelithiasis.[1] Decompression of the common bile duct (CBD) and removal of stones by en-

Cite this article as: Şenocak R, Çelik SU, Kaymak Ş, Hançerlioğulları O. Perioperative outcomes of the patients treated using laparoscopic cholecystectomy after emergent endoscopic retrograde cholangiopancreatography for bile duct stones: Does timing matter? Ulus Travma Acil Cerrahi Derg 2020;26:396-404. Address for correspondence: Süleyman Utku Çelik, M.D. Sağlık Bilimleri Üniversitesi Gülhane Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara, Turkey Tel: +90 312 - 304 20 00 E-mail: s.utkucelik@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):396-404 DOI: 10.14744/tjtes.2020.94401 Submitted: 11.03.2020 Accepted: 17.04.2020 Online: 13.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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doscopic methods are commonly accepted treatment methods in symptomatic and obstructive CBD stones. Various surgical methods, such as open or laparoscopic cholecystectomy (LC) with CBD exploration, laparoscopic-endoscopic rendezvous (LERV) technique or two-stage LC either before or after endoscopic sphincterotomy (ES) with endoscopic retrograde cholangiopancreatography (ERCP), are preferred when treating bile duct stones.[2] Although the outcomes of single-stage laparoscopic CBD exploration and LERV technique may be alternative or comparable to combined methods.[3,4] Currently, the most common procedure in many countries is the elective LC performed after preoperative ERCP and ES.[5] For patients with residual stones in the gallbladder after CBD stone removal with ERCP, the subsequent management of the gallbladder is still a subject to debate. While planned cholecystectomy after the wait-and-see policy or ES is recommended for residual stones in the gallbladder after endoscopic stone removal, there are also recent articles that suggest the administration of early cholecystectomy after ES to all patients with CBD stones and gallstones accompanied by co-morbidities or with stones eligible for surgery.[6] In the case of the wait-and-see policy after ES, 10–50% of patients may develop recurrent biliary events (RBE), so to decrease RBE rates, cholecystectomy may be performed as early as possible after ERCP rather than waiting for a long period of time. Early cholecystectomy recommended in 7–14 days after the initial admission has been shown in the literature to be cost-effective, to improve clinical outcomes, and to be a superior treatment regardless of ERCP in the treatment of acute cholecystitis and mild biliary pancreatitis.[7,8] However, the generalizability of this evidence to post ERCP patients is unproven. Moreover, previous studies have shown that the rate of conversion from laparoscopic to open cholecystectomy after a previous ES is as high as 8% to 55% versus less than 5% in patients with uncomplicated cholelithiasis.[4,9–13] Although there is no consensus regarding the optimal timing for cholecystectomy following therapeutic ERCP, in many countries, LC after ES is still practically performed after 4–6 weeks of delay. Reasons for this delay include logistical reasons, the assumption of full recovery from an acute illness before surgery and expecting inflammatory response to subside after six weeks.[8,9,11] In various studies and reviews, the interval from ERCP to LC has ranged from days to months, and conflicting results have been obtained. While some researchers advocated that an early interval led to more favorable outcomes (fewer conversion rates, less perioperative complications and length of hospital), some researchers found that time intervals had no influence on the course of laparoscopic procedure.[6–8,11–13] The present study aims to compare the effects of different time intervals between ERCP and LC on conversion to open cholecystectomy and perioperative outcomes. Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

MATERIALS AND METHODS This study was approved by Gulhane Military Medical Academy Ethics Committee (approval number: 506874691491-146-16/1648-436) and was conducted in accordance with the 1964 Helsinki Declaration and its later amendments. This study included 18-year-old or older patients who underwent a successful ERCP and endoscopic stone removal operation due to choledocholithiasis, had radiologically proven residual gallbladder stones, and underwent LC at the Department of General Surgery from among 550 patients who were diagnosed with cholestasis and underwent emergent ECRP between 2013 and 2016 at the Department of Gastroenterology. Patients who were not suitable for surgery (ASA V), and patients who had stones that could not be removed through ERCP and therefore had to undergo open surgery and ductal exploration or percutaneous transhepatic biliary drainage were not included in the study (Fig. 1). Demographics, ultrasonographic features of the gallbladder, such as thickness, content, and stones, ERCP notes, conversion rate and reasons, operative time, bile duct injuries, the need for a drain, and postoperative length of hospital stay were recorded. Complications were graded according to the Clavien-Dindo classification system.[14] On-admission biochemical parameters, including leucocyte, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, total and direct bilirubin and amylase, were also recorded. The decision on LC timings was made entirely based on the surgeon’s own planning or the severity of symptoms. All the surgeons who performed LC had extensive experience and a long learning curve. If the senior resident was performing the surgery, the decision to convert to open surgery was made after the intervention of the experienced surgeon. All surgical procedures were performed in a single center using a 4-port standard LC technique, and all patients received a single dose of prophylactic antibiotics on induction. The time interval between ERCP and cholecystectomy was determined by calculating the time in days between the last ERCP and the day of surgery. To examine the effects of the time intervals, the patients were divided into three groups as follows: patients who underwent surgery within the first two weeks (Group 1), patients who underwent surgery in between weeks two and six (Group 2) and patients who underwent surgery after >6 weeks (Group 3). Conversion from laparoscopic to open surgery and perioperative complications was investigated to be the primary outcome, and the effects of existing gallbladder pathology on the conversion from laparoscopic to open surgery was investigated as the secondary outcome. 397


Şenocak et al. Perioperative outcomes of the patients treated using LC after emergent ERCP for bile duct stones

550 patients with cholestasis who underwent ERCP were assesed for eligibility

Excluded (n=483) Missed or refused to operate (n=242) Enrollment

Previous history of abdominal surgery (n=58) Failed ERCP (n=23) PTBD Excluded (n=26) Complicated ERCP (n=39) Percutaneous cholecystostomy (n=27) Malign obstruction (n=68)

Group 1 (n=25)

Group2 (n=20)

Group 3 (n=22)

Cholecystectomy within <2 weeks

Cholecystectomy within 2–6 weeks

Cholecystectomy within >6 weeks

Follow-up

Lost to follow up (n=0)

Lost to follow up (n=0)

Lost to follow up (n=0)

Analysis

Allocation

Included for analysis (n=67)

Analyzed (n=25)

Analyzed (n=20)

Analyzed (n=22)

Figure 1. CONSORT flow diagram of this study. ERCP: Endoscopic retrograde cholangiopancreatography; ASA: American Society of Anesthesiologists.

Statistical Analysis All statistical analyses were performed using Statistical Package for the Social Sciences version 20.0 for Windows (IBM®, Chicago, USA). Descriptive statistics were expressed as means and standard deviations in normally distributed numeric variables, as medians and interquartile ranges (IQRs) in non-normally distributed numeric variables, and as counts and percentages in categorical variables. Whether the variables were normally distributed was examined using visual (histograms and probability graphs) and analytical methods (Shapiro-Wilk tests). It was found that only the age variable was normally distributed, but the other variables were not. In intergroup comparisons, a One-Way ANOVA was preferred for age, and Kruskal Wallis tests were preferred for other variables that were not normally distributed. Bonferroni correction was preferred in post-hoc analyses. Intergroup analyses of categorical variables were carried out using the Chi-square method. For all analyses, a p-value of <0.05 was considered to indicate statistical significance.

RESULTS Of the 550 patients who underwent consecutive ERCP during this study, only patients who underwent ERCP due to concurrent gallbladder and CBD stones were considered for eligibility. 398

A total of 67 patients were included in this study after accounting for the patients who were excluded from the study (Fig. 1). LC after ERCP was performed between days 0 and 176. Among the patients who were included in this study, 32 (47.8%) were males, and 35 (52.2%) were females with a mean age of 52.8±16.8 years. Gender distribution was similar among the groups (p=0.641). A statistically significant difference was found between the groups concerning age (p=0.018), and this difference was between Groups 2 and 3 based on the post hoc analysis (44.8 vs. 59.3 years, p=0.015). Of the patients, 35 were in ASA category I or II, 19 were in ASA category III, and 13 patients were in ASA category IV. The majority of the patients undergoing ERCP due to biliary pancreatitis and the patients with comorbidity were in Groups 1 and 3. No differences were found between the groups concerning ASA classification (p=0.102), presence of comorbidity (p=0.083) and presence of pancreatitis (p=0.408). However, it was seen that in patients with comorbidity and pancreatitis history, the tendency of the surgical team was to operate on the patients (72.4% vs. 64.4%, respectively) mainly in the late period. The demographic characteristics of the groups are shown in Table 1. Laboratory characteristics of the patients were found to be similar between groups. Gallbladder wall thickening was seen Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Şenocak et al. Perioperative outcomes of the patients treated using LC after emergent ERCP for bile duct stones

Table 1. Baseline demographic data according to the time interval Age, mean±SD (year)

Group 1 (n=25) <2 weeks

Group 2 (n=20) 2–6 weeks

Group 3 (n=22) >6 weeks

p

53.6±17.6

44.8±14.8

59.3±15.2

0.018

Gender 0.641 Female

13 (52.0)

12 (60.0)

10 (45.5)

Male

12 (48.0)

8 (40.0)

12 (54.5)

ASA score

0.102

I

5 (20.0)

8 (40.0)

1 (4.5)

II

7 (28.0)

7 (35.0)

7 (31.8)

III

7 (28.0)

4 (20.0)

8 (36.4)

IV

6 (24.0)

1 (5.0)

6 (27.3)

Comorbidity (+)

16 (64.4)

8 (40.0)

16 (72.7)

0.083

Biliary pancreatitis (+)

4 (16.0)

1 (5.0)

4 (18.2)

0.408

ASA: American Society of Anesthesiologists; SD: Standard deviation.

Table 2. Comparison of the laboratory and preoperative radiological features Leucocyte (106 x µL) Serum AST (U/L)

Group 1 (n=25) <2 weeks

Group 2 (n=20) 2–6 weeks

Group 3 (n=22) >6 weeks

p

7.4 (6.1–11.1)

7.1 (6.0–9.9)

7.8 (5.7–11.7)

0.845

83 (37–166)

109 (44–367)

76 (29–283)

0.629

Serum ALT (U/L)

204 (68–298)

154 (79–505)

108 (37–357)

0.523

Serum ALP (U/L)

179 (126–215)

184 (151–385)

159 (120–343)

0.324

Serum GGT (U/L)

255 (118–422)

233 (173–627)

433 (192–569)

0.199

1.7 (0.9–4.4)

2.3 (1.6–4.8)

1.6 (1.1–4.2)

0.467

Direct bilirubin (mg/dL)

0.4 (0.3–2.7)

1.1 (0.4–3.0)

1.1 (0.3–2.4)

0.530

Serum amylase (U/L)

132 (58–239)

63 (50–98)

68 (45–197)

0.117

Stone diameter (mm)

1 (1–9.5)

1 (1–12)

12 (1–20)

0.379

Total bilirubin (mg/dL)

Gallbladder wall thickness, n (%) <4 mm

21 (84.0)

17 (85.0)

18 (81.8)

≥4 mm

4 (16.0)

3 (15.0)

4 (18.2)

Gallbladder content, n (%) Sludge

11 (44.0)

9 (45.0)

10 (45.5)

Stone

14 (56.0)

11 (55.0)

12 (54.5)

0.960

0.995

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase. All data except gallbladder thickness and content are reported as median (IQR), these data are number (%).

in 16.0% (4/25) of the patients in Group 1, 15.0% (3/20) of the patients in Group 2, and 18.2% (4/22) of the patients in Group 3 (p=0.960). Moreover, the groups were similar concerning gallbladder content and median stone diameter (p=0.995 and p=0.379, respectively). The laboratory values and preoperative imaging results of the groups are shown in Table 2. The total conversion rate was found to be 19.4% (13/67). The highest rate was in Group 2 (25.0%, n=5), and the lowest Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

was in Group 3 (13.6%, n=3) (Fig. 2). However, no significant difference was detected between the groups in this regard (p=0.646). Conversion from laparoscopic to open surgery took place in eight of the 32 male patients (25.0%) and five of the 35 female patients (14.2%). Median operating time was 80 min in Group 1, 71 min in Group 2, and 75 min in Group 3. Median postoperative length of stay was three days in Group 1, 2.5 days in Group 2, and four days in Group 3. However, no statistically significant differences were found between the groups regarding operating times or postoperative length of 399


Şenocak et al. Perioperative outcomes of the patients treated using LC after emergent ERCP for bile duct stones

median time interval between ERCP and LC (p=0.284) (Table 4). Considering the reasons for conversion to open surgery, the main reason was anatomical ambiguity in 46.2% (n=6) of 13 patients, adhesion in 38.4% (n=5), and bleeding in 15.4% (n=2). Bleeding was more pronounced in the early group, whereas adhesion was more pronounced in the late groups. There was no significant difference in the distribution of the reasons for conversion to open surgery among the groups (p=0.582). No mortality was recorded in any of the groups (Table 5).

p=0.562 30

p=0.688

p=0.349

Conversion rate (%)

20

DISCUSSION

10

0

Group 1

Group 2

Group 3

Figure 2. Conversion rates for time interval groups.

stay (p=0.861 and p=0.634, respectively). Most complications were minor (Clavien-Dindo grade I), and there was no statistically significant difference between the groups concerning postoperative complications (p=0.289). Overall ClavienDindo grade II and III complication rate was 17.9%. In the group undergoing LC after >6 weeks, only two Clavien-Dindo grade III complications occurred. These complications were bile leaks from the cystic duct and managed with endoscopic interventions (Table 3). When the patients who underwent conversion from laparoscopic surgery to open surgery were compared with the patients who were operated on fully laparoscopically, there was no difference between the groups concerning mean age (p=0.698), gender (p=0.268), preoperative gallbladder wall thickness (p=0.911), gallbladder content (p=0.176) and the

Patients with cholelithiasis and choledocholithiasis require treatment of both of these entities.[13,15,16] Although there are several strategies for the treatment of combined choledochocystolithiasis, a commonly used strategy to treat patients is the two-stage management using preoperative ERCP with endoscopic sphincteroplasty and CBD stone removal followed by an interval LC.[3,9,17,18] With the widespread adoption of laparoscopy, single-stage treatments, such as CBD exploration and LERV techniques, have evolved with LC.[4,7,13,17,19–21] The combination of LC and laparoscopic bile duct exploration (LBDE) allows for both removal of the gallbladder and treatment of CBD stones in the same stage. However, for LC and LBDE performed together in a single-stage, not only that a flexible choledochoscope is necessary together with a light source and a camera, and disposable instrumentations, such as baskets, balloons, and stents, but also that bile duct surgery is associated with a significant learning curve for both surgeons and staff.[4,8,10,20,22,23] For this reason, a single-stage surgery may seem to be the ideal option for patients who undergo combined cholelithiasis and choledocholithiasis, but today, this treatment strategy cannot be implemented by many surgeons. In this case, surgeons usually prefer an interval LC as an option of treatment. However, this time interval be-

Table 3. Comparison of groups according to operative time, conversion rate, hospital stay, usage of the drain, and postoperative complications

Group 1 (n=25) <2 weeks

Group 2 (n=20) 2–6 weeks

Group 3 (n=22) >6 weeks

Type of operation, n (%)

LC completed

Conversion to OC

Operation time (min) Length of stay (day) Drain (+), n (%)

20 (80.0)

15 (75.0)

0.646

19 (86.4)

5 (20.0)

5 (25.0)

3 (13.6)

80 (60–120)

71 (60–101)

75 (68–96)

0.861

3 (1–6)

2.5 (1–5)

4 (2–5)

0.634

10 (40.0)

13 (65.0)

10 (45.5)

0.227

Clavien-Dindo classification, n (%)

p

I

11 (73.3)

8 (66.7)

II

4 (27.7)

4 (34.3)

2 (15.4)

III

0

0

2 (15.4)a

0.289

9 (69.2)

LC: Laparoscopic cholecystectomy; OC: Open cholecystectomy. All data except operation time and length of stay are number (%), these data are reported as median (IQR) abile leak from the cystic duct or stump.

400

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Table 4. Relationship between conversion to open and disease of the gallbladder

Full laparoscopic (n=54)

Conversion to open (n=13)

p

Age, mean±SD (year)

52.5±17.1

54.1±16.5

0.698

Male, gender, n (%)

24 (44.4)

8 (61.5)

0.268

Gallbladder content, n (%) Sludge

22 (40.7)

8 (61.5)

Stone

32 (59.3)

5 (38.5)

Gallbladder wall thickness, n (%) Normal (<4 mm)

45 (83.3)

11 (84.6)

Increased (≥4 mm)

9 (16.7)

2 (15.4)

77 (60–100)

72 (60–120)

Time interval between ERCP and LC (day)

0.176

0.911

0.284

ERCP: Endoscopic retrograde cholangiopancreatography; LC: Laparoscopic cholecystectomy; SD: Standard deviation. Time interval between ERCP and LC are reported as median (IQR).

Table 5. Reason for conversion of laparoscopic cholecystectomy (n=13)

Group 1

Group 2

Group 3

n

%

Adhesion

3

2

5

38.4

Hemorrhage

2

2

15.4

Anatomic

3

2

1

6

46.2

5

5

3

13

100

uncertainty Total

tween ERCP and LC ranges from days to months.[9,15,21] When viewed from this perspective, there is a paradoxical problem that needs to be resolved because a single-stage operation requires experience, and a two-stage operation has the risk of leading to recurrent attacks and increased complication rates if not carried out within the appropriate time frame. In this study, we analyzed the intraoperative and postoperative outcomes of the patients undergoing LC at three different time intervals after emergent ERCP. LC after ERCP with or without ES is a more complex procedure and is generally associated with a higher rate of conversion than standard LC with no previous intervention.[10,24,25] Thus, the timing of LC after ERCP is a critical factor affecting the outcome. On the other hand, patients are at higher risk of RBE while waiting for a delayed cholecystectomy compared with patients who undergo an early cholecystectomy. [26] However, some surgeons tend to postpone the main surgical procedure of the patients who have previously undergone ERCP (a time interval of 6–8 weeks or more) to be able to perform cholecystectomy in an optimal condition, to allow the gallbladder area to cool off and the patients to recover from the acute illness and inflammation and at the end.[13] Sometimes, surgical procedure is delayed for logistical reasons or choice of patients.[24] Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

It has been stated that the rate of conversion to open cholecystectomy is less than 5% after LC performed on uncomplicated gallbladder disease patients and that this rate varies between 8–55% after ERCP.[13,17,27] The cause of such high conversion rates is explained by that post-ES bile reflux and bacterial contamination cause inflammation and adhesions around the Calot’s triangle and gallbladder.[12,25,28] In a study comparing the optimal time to achieve a better outcome, de Vries et al.[9] found a higher rate of conversion (31%) in patients undergoing LC 2–6 weeks after the ERCP procedure. They determined that the conversion rate was 4% in patients undergoing LC in the first two weeks after ERCP, and the rate was 16% after >6 weeks. They found that there was a significant difference concerning the rate of conversion between the patients who were operated on in the first two weeks after ERCP and patients who were operated on in 2–6 weeks after ERCP. However, the severity of adhesions encountered during the procedures, bile duct injury, and the time needed to perform the LC were not found to be influenced by the interval between ERCP and LC. Similarly, Bostanci et al.[11] found that the higher conversion rates were not associated with the time interval between ERCP and LC or with the performance of stone extraction during ERCP. These rates were found to be associated with the number of ERCPs performed before surgery. In another study conducted by Salman et al.,[12] patients were divided into two groups — patients who underwent LC 24–72 hours after ERCP and patients who underwent surgery 72 hours–7 days after ERCP — and the conversion rate was found to be statistically significant in the delayed LC group compared to the early LC group (17.5% vs. 2.5%, respectively, p=0.02). A recent systematic review conducted by Friis et al.[29] showed an increase from a 4.2% conversion rate when LC was performed within 24 h of ERCP to 7.6% when performed after 24–72 h delay, to 12.3% when performed within two weeks and 2–6 weeks, and to a 14% conversion rate when the operation was performed more than six weeks after ERCP. The authors suggested that chole401


Şenocak et al. Perioperative outcomes of the patients treated using LC after emergent ERCP for bile duct stones

cystectomy can be carried out safely within the first 24–72 h of ERCP to reduce the conversion rate and perioperative complications. Although the time interval between ERCP and cholecystectomy has been described as early or delayed, the definitions of “early” or “delayed” differ across studies. In many studies, early cholecystectomy has been defined as an operation within two or three days after ERCP, whereas in some others, it has been defined as an operation within two weeks of ERCP. Moreover, late cholecystectomy definitions vary to include 2–8 weeks after ERCP. Apart from the studies in which patients were divided into patients undergoing early and late cholecystectomy, in many other studies, these intervals were studied by being divided into three different time intervals. Moreover, patients’ inclusion and exclusion criteria had high heterogeneity. In the current study, the patients were divided into three groups to cover all time intervals as patients who underwent surgery within the first two weeks, patients who underwent surgery 2–6 weeks, and patients who underwent surgery after >6 weeks. Overall, the rate of conversion to open laparotomy was 19.4%, and this rate is comparable with the larger series. The highest conversion rate was in the group of patients who were operated on 2–6 weeks after ERCP (25.0%), and the lowest conversation was in the group of patients who were operated on six weeks after ERCP (13.6%). The results of this study suggested that the time interval from the ERCP procedure to LC was not a significant factor for conversion to open cholecystectomy. Although there was no statistically significant difference in the rates, conversion to open surgery took place at all-time intervals. However, it was seen that the subacute period after ERCP was a more critical time frame for conversion to open surgery. Many studies have not specified any difference between groups concerning the rates of conversion to open surgery, but they have shown results showing the advantages of early cholecystectomy concerning other factors. El Nakeeb et al.[28] conducted a study by dividing patients into two groups as early LC (within three days after ERCP) and late LC (one month after ERCP). They found no difference between the groups concerning the conversion rate. However, recurrent biliary symptoms and morbidity rates were found to be significantly higher in the late LC group than in the early group. Similarly, Reinders et al.[13] reported that the conversion rate, postoperative complications, hospital stay, and postoperative pain were comparable between groups. They also showed that early LC was likely to minimize the risk of RBE compared with delayed LC. Kwon et al.[17] designed a study to evaluate a total of 305 patients who underwent cholecystectomy after ERCP, where they found the rate of conversion to open cholecystectomy as 15.7%. The rate was 14.5% <2 weeks after ERCP, 18.4% 2–6 weeks after ERCP, and 15.6% >6 weeks after ERCP. In their study, in which the period between ERCP and surgery was divided into three groups, they found no statistical difference in the conversion rate among different time 402

intervals. They revealed that cholecystitis (OR 1.90), mechanical lithotripsy (OR 6.13), and two or more CBD stones (OR 2.20) were significant risk factors for conversion to open cholecystectomy. In a recent study, Aziret et al.[30] examined the time interval between ERCP and LC in three groups as early (48–72 h), moderate (72 h–6 weeks), and delayed (6–8 weeks). They showed that the early LC was associated with shorter operation time, lesser hospital readmissions, fewer fibrotic changes in the gallbladder, and lower complication rates, but not with conversion rates. In this study, the time interval from ERCP to LC was not a significant factor for postoperative complications, operation time, drain usage, or length of hospital stay. Conversion to open surgery was higher in male patients than in female patients (25.0% vs. 14.2%), indicating that LC is more difficult and is a risk factor for conversion to open surgery in male patients. One of the important findings of the current study was that the patients in Group 3 (>6 weeks after ERCP) were older (mean age 59.3 years) (p=0.018), and their accompanying comorbidity rates were higher than in other groups, indicating that patient-related factors were an effective factor on the time interval. No difference was found among the patients who were transitioned to open surgery and patients who were operated fully laparoscopically concerning age, gender, gallbladder wall thickness or content, and time interval, supporting the idea that not only the time interval but also patient-related or procedural factors, such as concomitant cholangitis, cholecystitis, pancreatitis, stent insertion, and the number of procedures can play a more effective role in the conversion to open surgery. Some authors found that among patients who undergo LC, preoperative ERCP might be associated with more common intra- and post-operative complications according to time intervals. Another point that stood out in the studies that were examined was that there were differences regarding the incidence of complications, such as perioperative uncontrolled bleeding, gallbladder rupture, CBD injury and bile leakage from the bed or the cystic stump concerning time intervals after ERCP.[9,11,30] Beliaev et al.[15] conducted a study examining the effects of LCs performed at different time intervals after ERCP on the ratio of major bile duct injuries, where the late (≥16 weeks) LC was found to be associated with a 10-fold increase in major bile duct injuries. In our study, there was no statistically significant difference in perioperative complications among the patients who underwent LC >2 weeks, 2–6 weeks and >6 weeks after ERCP. The rate of Clavien-Dindo grade II and III complications was 17.9% (12 of 67 patients). Concerning major complications, two patients in the group undergoing LC after >6 weeks developed Clavien-Dindo grade III complications. These were bile leaks from the cystic duct and were managed with endoscopic interventions. The procedure is completed through laparoscopic subtotal cholecystectomy, and there may be more bile leaks from the cystic stump due also to the high prevalence of adhesions in the late group. Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Şenocak et al. Perioperative outcomes of the patients treated using LC after emergent ERCP for bile duct stones

Thus, serious bile duct problems may occur. For this reason, it has been recommended that the surgery be performed by an experienced laparoscopic surgeon to reduce both conversion rates and complications in LC performed after ERCP. Single-stage treatment (LBDE during LC) clearly has the advantage of the immediate treatment of both CBD stones and cholelithiasis. However, because of the lack of experienced surgeons or organizational restrictions, delayed LC is often chosen as the standard treatment of patients who have gallbladder and CBD stones and have undergone ERCP in many European countries as well as our country.[18,24,26] In this situation, another main problem that emerges is RBEs waiting to undergo surgery. In our study, the results suggest that none of the time intervals was superior to the others regarding the conversion rates and postoperative complications. This may be because all surgical procedures were performed or supervised by experienced surgeons or due to appropriate patient selection. However, this study has several limitations. First, because of the retrospective nature of this study, the data were collected from the surgical reports and patients’ file. Second, this study comprises a small sample size; however, we believe that this study can provide new insights into the literature compared to the effects of different time intervals between ERCP and LC. In addition, there are limited data regarding the number of biliary cannulations during ERCP. Finally, we did not evaluate the RBEs occurring in the interval between ERCP and cholecystectomy. In conclusion, our results support the notion that LC after an ERCP procedure is more complex and difficult and has higher conversion rates than LC for uncomplicated cholelithiasis. In this retrospective analysis, although no significant effect of different time intervals between ERCP and LC on perioperative outcomes was demonstrated in patients with CBD stones concomitant with cholelithiasis, the subacute period after ERCP is a critical period of time to convert to open surgery. Considering that serious complications may develop in the late period and RBEs may take place, LC after ERCP is recommended to be performed in the early period. It is possible to reduce conversion rates and complications only by considering the time interval only if surgeries are performed by advanced laparoscopic surgeons. For more accurate results, it is necessary to conduct more prospective studies where patients are randomly evaluated, and time intervals are determined by sharp limits. Ethics Committee Approval: This study was approved by Gulhane Military Medical Academy Ethics Committee (approval number: 50687469-1491-146-16/1648-436) and was conducted in accordance with the 1964 Helsinki Declaration and its later amendments. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: R.Ş., Ş.K., O.H.; Design: R.Ş., S.U.Ç., Ş.K., O.H.; Supervision: R.Ş.; Fundings: R.Ş., S.U.Ç., Ş.K., O.H.; Materials: R.Ş., Ş.K.; Data: R.Ş., Ş.K., O.H; Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

Analysis: R.Ş., S.U.Ç.; Literature search: R.Ş., S.U.Ç.; Writing: R.Ş., S.U.Ç.; Critical revision: R.Ş., S.U.Ç., Ş.K., O.H. Conflict of Interest: None declared. Financial Disclosure: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Şenocak et al. Perioperative outcomes of the patients treated using LC after emergent ERCP for bile duct stones 14. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205–13. 15. Beliaev AM, Booth M. Late two-stage laparoscopic cholecystectomy is associated with an increased risk of major bile duct injury. ANZ J Surg 2016;86:63–8. 16. Trejo-Ávila M, Solórzano-Vicuña D, García-Corral R, Bada-Yllán O, Cuendis-Velázquez A, Delano-Alonso R, et al. Laparoscopic cholecystectomy after endoscopic treatment of choledocholithiasis: a retrospective comparative study. Updates Surg 2019;71:669−75. 17. Kwon YH, Cho CM, Jung MK, Kim SG, Yoon YK. Risk factors of open converted cholecystectomy for cholelithiasis after endoscopic removal of choledocholithiasis. Dig Dis Sci 2015;60:550–6. 18. Williams E, Beckingham I, El Sayed G, Gurusamy K, Sturgess R, Webster G, et al. Updated guideline on the management of common bile duct stones (CBDS). Gut 2017;66:765−82. 19. Saccomani G, Durante V, Magnolia MR, Ghezzo L, Lombezzi R, Esercizio L, et al. Combined endoscopic treatment for cholelithiasis associated with choledocholithiasis. Surg Endosc 2005;19:910−4. 20. Mo LR, Chang KK, Wang CH, Yau MP, Yang TM. Preoperative endoscopic sphincterotomy in the treatment of patients with cholecystocholedocholithiasis. J Hepatobiliary Pancreat Surg 2002;9:191–5. 21. Schiphorst AH, Besselink MG, Boerma D, Timmer R, Wiezer MJ, van Erpecum KJ, et al. Timing of cholecystectomy after endoscopic sphincterotomy for common bile duct stones. Surg Endosc 2008;22:2046−50. 22. Martin DJ, Vernon DR, Toouli J. Surgical versus endoscopic treatment of bile duct stones. Cochrane Database Syst Rev 2006;(2):CD003327. 23. Vettoretto N, Arezzo A, Famiglietti F, Cirocchi R, Moja L, Morino M. Laparoscopic-endoscopic rendezvous versus preoperative endoscopic sphincterotomy in people undergoing laparoscopic cholecystectomy for

stones in the gallbladder and bile duct. Cochrane Database Syst Rev 2018;4:CD010507. 24. Manes G, Paspatis G, Aabakken L, Anderloni A, Arvanitakis M, AhSoune P, et al. Endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy 2019;51:472−91. 25. Reinders JS, Gouma DJ, Heisterkamp J, Tromp E, van Ramshorst B, Boerma D. Laparoscopic cholecystectomy is more difficult after a previous endoscopic retrograde cholangiography. HPB (Oxford) 2013;15:230–4. 26. Huang RJ, Barakat MT, Girotra M, Banerjee S. Practice Patterns for Cholecystectomy After Endoscopic Retrograde Cholangiopancreatography for Patients With Choledocholithiasis. Gastroenterology 2017;153:762–71.e2. 27. Genc V, Sulaimanov M, Cipe G, Basceken SI, Erverdi N, Gurel M, et al. What necessitates the conversion to open cholecystectomy? A retrospective analysis of 5164 consecutive laparoscopic operations. Clinics (Sao Paulo) 2011;66:417−20. 28. El Nakeeb A, Ezzet H, Askar W, El Hanafy E, Hamdy E, Atef E, et al. Early Versus Late Cholecystectomy After Clearance of Common Bile Duct Stones by Endoscopic Retrograde Cholangiopancreatography: A Prospective Randomized Study. Surg Laparosc Endosc Percutan Tech 2016;26:202−7. 29. Friis C, Rothman JP, Burcharth J, Rosenberg J. Optimal Timing for Laparoscopic Cholecystectomy After Endoscopic Retrograde Cholangiopancreatography: A Systematic Review. Scand J Surg 2018;107:99– 106. 30. Aziret M, Karaman K, Ercan M, Vargöl E, Toka B, Arslan Y, et al. Early laparoscopic cholecystectomy is associated with less risk of complications after the removal of common bile duct stones by endoscopic retrograde cholangiopancreatography. Turk J Gastroenterol 2019;30:336−44.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Safra kanalı taşları için yapılan acil endoskopik retrograd kolanjiyopankreatografi sonrası laparoskopik kolesistektomi uygulanan hastaların perioperatif sonuçları: Zamanlama önemli mi? Dr. Rahman Şenocak, Dr. Süleyman Utku Çelik, Dr. Şahin Kaymak, Dr. Oğuz Hançerlioğulları Sağlık Bilimleri Üniversitesi Gülhane Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara

AMAÇ: Koledokolitiyazis nedeni ile acil endoskopik retrograd kolanjiyopankreatografi (ERCP) yapılan hastalarda laparoskopik kolesistektomi (LK) için optimal zamanlama konusunda fikir birliği yoktur. Her ne kadar bazı veriler erken dönemde cerrahinin veya tek aşamalı LK ile birlikte yapılan laparoskopik safra kanalı eksplorasyonunun daha olumlu sonuçlara sahip olduğunu düşündürse de deneyim eksikliği, gerekli malzeme yokluğu veya klinik kısıtlılıklar nedeniyle geç dönem LK çoğunlukla ERCP sonrası sebat eden safra taşı olan hastaların standart tedavisi olarak tercih edilmektedir. Bu çalışmanın amacı, ERCP ve LK arasındaki farklı zaman aralıklarının perioperatif sonuçlar üzerindeki etkilerini değerlendirmektir. GEREÇ VE YÖNTEM: ERCP ile ana safra kanalı taşları tedavi edilen ve daha sonra LK uygulanan ardışık hastaların ameliyat öncesi ve sonrası verileri geriye dönük olarak incelendi. Farklı zaman aralıklarının sonuçlar üzerindeki etkisini değerlendirmek için hastalar son yapılan ERCP’den LK’ye kadar geçen süreye göre üç gruba ayrıldı: 2 hafta içinde (Grup 1), 2–6 hafta arasında (Grup 2) ve 6 haftadan sonra (Grup 3). BULGULAR: Bu çalışmada ortalama yaşı 52.8 olan toplam 67 hasta analiz edildi. Olguların kapalı ameliyattan açığa geçme oranı Grup 1’de %20, Grup 2’de %25 ve Grup 3’te %13.6 idi (p=0.646). Bu oran erkek hastalarda %25 ve kadınlarda ise %14.2 olarak hesaplandı. Gruplar arasında cinsiyet, yandaş hastalık, laboratuvar ve safra kesesi özellikleri, ameliyat süresi ve hastanede kalış süresi açısından anlamlı fark bulunmadı. Perioperatif komplikasyon oranı %17.9 bulundu; ancak gruplar arasında komplikasyon oranı açısından anlamlı fark saptanmadı (p=0.289). TARTIŞMA: Bu çalışmadan elde edilen sonuçlar, ERCP sonrası yapılan LK’nin komplike olmayan standart kolelitiazis için yapılan LK’den daha kompleks ve daha yüksek açığa geçiş oranına sahip olduğunu desteklemektedir. Kolelitiazise eşlik eden ana safra kanalı taşları olan hastalarda ERCP sonrasında farklı zaman aralığında uygulanan LK’nin perioperatif sonuçlar üzerinde anlamlı bir etkisi görülmemesine rağmen, LK’nin açık cerrahiye geçmesi açısından ERCP’den sonraki 2–6 hafta kritik bir dönemdir. Ayrıca geç dönemde yapılan LK’de ciddi komplikasyonların ortaya çıkabileceği ve tekrarlayan biliyer atakların olabileceği göz önünde bulundurulduğunda ERCP sonrası LK’nin erken dönemlerde yapılması önerilir. Anahtar sözcükler: Endoskopik retrograd kolanjiyopankreatografi; koledokolitiazis; kolelitiazis; komplikasyon; laparoskopik kolesistektomi. Ulus Travma Acil Cerrahi Derg 2020;26(3):396-404

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doi: 10.14744/tjtes.2020.94401

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ORIGIN A L A R T IC L E

Evaluation and comparison of tick detachment techniques and technical mistakes made during tick removal Ahmet Rıza Şahin, M.D.,1 Hakan Hakkoymaz, M.D.,2 Ali Muhittin Taşdoğan, M.D.,3 Ekrem Kireçci, M.D.4 1

Department of Infectious Diseases and Clinical Microbiology, Kahramanmaraş Sütçü İmam Univesity Faculty of Medicine,

Kahramanmaraş-Turkey 2

Department Emergency Medicine, Kahramanmaraş Sütçü İmam Univesity Faculty of Medicine, Kahramanmaraş-Turkey

3

Hasan Kalyoncu University Health Sciences Faculty, Gaziantep-Turkey

4

Department of Medical Microbiology, Kahramanmaraş Sütçü İmam Univesity Faculty of Medicine, Kahramanmaraş-Turkey

ABSTRACT BACKGROUND: Tick is among the important ectoparasites of humans and animals. Ticks may transmit disease-causing pathogens to humans. Tick contact may be resulted in several viral and bacterial infections, including Crimean-Congo Hemorrhagic Fever. Timely removal of ticks with appropriate methods is important in prevention of disease transmission. There are many methods reported for tick detachment. In this study, we aimed to evaluate two of them, suture lassoing and freezing and to compare both methods and to examine technical mistakes with these techniques. METHODS: This study was designed as a prospective cross-sectional study, and included the ticks detached by healthcare professionals or directly by patients who presented to the emergency department due to tick contact. The ticks were recorded as larvae, nymphs, and adults according to their growth period. Ticks detachment types with surgical sutures and removal mistakes were recorded. RESULTS: The majority (77.4%) of the ticks were removed by healthcare professionals and a lower rate by patients themselves with hand (22.6%). No technical mistake was found in 72 (77.4%) patients, and the tick was detached as a whole, while detached broken in 15 (16.1%) patients, and the tick was detached as a whole, but the sutures were attached wrong in six (6.5%) patients. Tick broken off due to technical mistakes was most commonly seen in the ticks removed by the individuals themselves. CONCLUSION: The results of this study suggest that when appropriately and correctly used, both suture lassoing and tweezers are effective in tick removal. Public awareness-raising and training programs should be increased on this issue. Keywords: Suture lassoing technique; tick; tick removal; tweezers technique.

INTRODUCTION Tick is among the important ectoparasites of humans and animals. Twenty-eight tick species known to feed on humans play a role as a vector in disease transmission.[1] Ticks are important concerning diseases with high mortality, which they mediate the transmission and public health. Crimean-congo hemorrhagic fever (CCHF), which is a tick-borne viral disease and affects a wide geographic area, including Turkey, Iran,

Russia, and many Eurasian countries, has led to increased global awareness and implementation of control programs. [2] CCHF disease was seen in our country for the first time in 2002, and Turkey is the most affected country with over 10000 definitive diagnoses and more than 500 deaths. These high figures have caused panic in the country, and 300000 presentations a year have been reached due to tick attachment. [2,3] Turkish Ministry of Health has established a strong Fighting Structure against ticks through registry system, guidelines,

Cite this article as: Şahin AR, Hakkoymaz H, Taşdoğan AM, Kireçci E. Evaluation and comparison of tick detachment techniques and technical mistakes made during tick removal. Ulus Travma Acil Cerrahi Derg 2020;26:405-410. Address for correspondence: Ahmet Rıza Şahin, M.D. Kahramanmaraş Sütçü İmam Üniv. Tıp Fak., Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabli Dalı, Kahramanmaraş, Turkey Tel: +90 344 - 300 10 00 E-mail: drahmetrizasahin@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):405-410 DOI: 10.14744/tjtes.2020.59680 Submitted: 13.09.2019 Accepted: 02.05.2020 Online: 15.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Şahin et al. Evaluation and comparison of tick detachment techniques and technical mistakes made during tick removal

interventional algorithms and educations.

Ticks Detached by

It has been shown that ticks’ time of feeding on the host they attached, and detachment of ticks with appropriate technique and timely are crucial in disease transmission.[4] The size of the epidemic in Turkey has brought effectiveness and sufficiency of tick detachment methods up for discussion. In the recent public guidelines published by the Turkish Ministry of Health, it was stated that a tick could be removed with a cloth or bag without touching once it is noticed.[5]

Residents (12%)

Intern doctors (13%)

In the present study, we aimed to investigate and compare tick detachment techniques and detachment mistakes in patients who presented to our University Hospital with the complaint of tick attachment.

Emergency medicine technicias (53%)

Patients (23%)

MATERIALS AND METHODS This study was designed as a prospective cross-sectional study and included the patients who presented to the emergency department of Kahramanmaras Sutcu Imam Unıversity with complaints of tick contact between May 2017 and September 2017. Written informed consent forms were received from the participants. Healthcare professionals were not intervened about techniques of tick detachment. The tissue site of tick removal was examined by healthcare professionals and whether any tick piece remained was recorded. The ticks collected were put into 50% ethyl alcohol containing numbered bottles. The ticks were examined by a single microbiologist under the stereotypical microscope, and their species were identified. The ticks were recorded as larvae, nymphs, and adults according to their growth period. The ticks were imaged and determined based on the breakdown or injury of the mouthpart. Ticks detachment types with surgical sutures and removal mistakes were imaged and defined.

Statistical Analysis

Figure 1. Distribution of the ticks according to the persons who removed them.

Healthcare professionals used sutures (lassoing) in 46 (63.88%) ticks, and tweezers in 26 (36.12%) ticks. Of the sutures used, 54.35% were monofilament and 45.65% polyfilament suture materials. No 5 suture material was the most commonly type Table 1. Demographic characteristics of the patients who presented to the emergency department with tick contact Demographic feature

n

%

Gender Male

64

68.8

female

29

31.2

34

36.6

County of tick contact

Data obtained from the study were recorded in SPSS 20.0 statistical software. Paired variables were compared using the Chi-square test. P<0.05 values were considered statistically significant.

Dulkadiroglu

23

24.7

Goksun

11

11.8

Andirin

7

7.5

RESULTS

Afsin

6

6.5

A total of 93 patients who presented to the emergency department with tick contact were included in this study. Of the patients, 68.82% were male and 31.18% were female. The mean age was found as 41.88±14.46 years. The majority of the patients who presented with a history of tick contact were resident in Onikisubat (36.56%) and Dulkadiroglu (24.73%) counties. It was found that majority of the ticks (77.42%) were removed by healthcare professionals, and by the patients themselves by holding with hand and pulling back at a lower rate (22.58%) (Fig. 1). The demographic characteristics of patients who presented to the emergency department with tick contact are given in Table 1. 406

Onikisubat

Turkoglu

4

4.3

Elbistan

2

2.2

Pazarcik

2

2.2

Nurhak

2

2.2

Caglayancerit

2

2.2

The person who removed the tick

Emergency medicine technician

49

52.7

Patient herself/himself

21

22.6

Intern doctor

Resident

12

12.9

11

11.8

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Table 2. Stage and types of the ticks Tick

n %

Stage Nymph

17

18.3

Adult

76

81.7

Species

Rhipicephalus sanguineus

41

44.1

Hyalomma spp.

26

27.1

Ixodes spp.

7

7.5

Could not be typed because it

7

7.5

was a nymph

Could not be typed because it was

12

12.9

broken down

(52.17%) followed by No 4 and No 3 (17.39%–17.36%) as the second most commonly, and No 2 and No 1 (6.52%–6.52%) as the least commonly used materials. Twelve (12.90%) ticks could not be typed since they were entirely broken down. Staging and typing of the ticks were performed after the removal and summarized in Table 2. The mean removal time of the ticks was found as 32.14±30.69 when detached by the affected persons themselves, 38.54±7.50 when removed with suture materials, and 39.88±39.58 when removed with the tweezer method. When the contact area was checked after detachment of the ticks, mouthparts of the tick was still in the tissue in 15 (16.13%) patients. When removal of the ticks was examined for technical mistakes, no any technical mistake was found in 72 (77.42%) patients and the tick was detached as a whole, while detached broken in 15 (16.13%) patients, and the tick was detached as a whole, but the sutures were attached wrong in six (6.45%)

patients. All sutures with mistakes were No 1 (n=3, 50%) and No 2 (n=3, 50%), and this caused statistically significant differences when compared to the other suture numbers (p<0.001). Suture mistakes during the detachment are shown in Figure 2. Tick broken off due to technical mistakes was most commonly seen in the ticks removed by the individuals themselves. Comparison of detachment methods and technical mistakes is summarized in Table 3. When technical mistakes during removal were examined according to the development stages of ticks, mistakes in the break down during removal and wrong suture lassoing were much higher in the ticks at the nymph stage. The comparison of technical mistakes by stages is given in Table 4. When the participants who removed the ticks and technical mistakes were compared, technical mistakes were much higher when the person who removed the tick was the person with tick contact (Fig. 3).

DISCUSSION Tick is a blood-feeding ectoparasite of domestic and wild animals and a vector that transmits disease-causing pathogens to humans worldwide.[6] Ticks are considered as the second most common vector for human diseases after mosquitos, but it is the most important vector of disease-causing pathogens in domestic and wild animals. Ticks are thought to be responsible for over 100000 cases all over the world. [7] Tick-borne bacterial and viral infections are observed in our country, including Crimean –Congo Hemorrhagic Fever (CCHF), babesiosis, theileriosis, cytauxzoonosis, hepatozoonosis, anaplasmosis, ehrlichiosis, aegyptianelosis, tickborne typhus, Lyme borreliosis, tularemia, bartonellosis and LSD.[8] Tick bites may cause complications, such as impetigo, ecthyma, cellulitis, erysipelas and shallow, painful, purulent ulcers.[9]

Figure 2. Ticks are detached as a whole, but the suture lassoing is wrong.

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Ĺžahin et al. Evaluation and comparison of tick detachment techniques and technical mistakes made during tick removal

Table 3. Comparison of the detachment techniques and technical mistakes Detachment technique

Technical mistake

No mistake whole tick

Tick broken off

Whole tick suturing wrong

10

11

0

By patients themselves

Total

p

21

Suture lassoing

40

0

6

46

Tweezers

22

4

0

26

Total

72 15

<0.001

6 93

Table 4. Comparison between the development stage of the ticks and technical mistakes Development stage

Technical mistake

No mistake whole tick

Tick broken off

Total

p

Whole tick suturing wrong

Nymph

7

8

2

Adult

65

7

4 76

Total

72 15

In the cases of tick attachment, timely removal of the attached ticks with appropriate methods is of paramount importance in the prevention of disease transmission.[10–12] Ticks should be detached as soon as possible because the risk for disease transmission significantly increases 24 hours after the tick attachment. In addition to a timely detachment of ticks, it should be completely removed, including mousepart and the cement secreted by the tick to secure the attachment. The inappropriate detachment of tick may cause mousepart break off in the skin, leading to infection or granuloma formation. Various techniques have been described for tick removal. Among these, the most studied methods in the literature included card-detachment technique, lassoing technique, freezing method, and tweezers method.[13] However, wrong suture thickness selection may cause regurgitation of the tick due to compression to the abdominal region. This is a high

60

Tick break off (%) 53

50 40 30 20 10 0

Patients

8

6

Intern doctor

Emergency medicine technician

Resident

Figure 3. Tick break off percentages by the persons who removed them.

408

17 <0.001

6 93

risk, especially in nymphs. In addition, several mechanical, chemical, and physical techniques, such as the use of sharp forceps, crush or squeezing the tick, application of various agents, such as gasoline and lidocaine, burning with match, and manual removal of the tick by twisting; however, scientific evidence to support these methods are limited. It has been shown that chemical applications may cause saliva discharge and intestinal secretions.[14] In our study, removal methods with suture lassoing and tweezers were investigated. In the literature, tick contact cases have been reported to more commonly occur in the June-September period.[15,16] Our study also was conducted between May and September. During this period, agriculture and stockbreeding activities are more common compared to other periods of the year, and this increases the risk for tick contact. In our study, 68.8% of the patients who presented to the emergency department due to tick contact were male. In a study by Al et al.,[17] this rate was reported as 64%. In a study conducted by Ulug et al.,[16] 62% of the patients who presented with a history of tick contact were male. Our result is similar to the previous studies. We think this may be because of the higher involvement of men in agriculture and stockbreeding activities in the region of the study. The majority (77.42%) of the ticks were removed by healthcare professionals, and a lower rate by patients themselves with hand (22.58%). In a similar study from our country, 74% of tick removal was performed by healthcare staff, and 24% by patients themselves.[16] Turkish Ministry of Health recommends that if the tick cannot be detached using gloves, clothes or a bag once the tick is noticed by the individuals themselves, they should present to a healthcare center.[18] In our study, there were 21 patients who detached the tick Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Şahin et al. Evaluation and comparison of tick detachment techniques and technical mistakes made during tick removal

themselves following this recommendation. The highest rate of mistake was found with the tick removal by the patients themselves. Of 21 ticks removed by the patients, 53% were broken off. Tick removal with tweezers is a commonly used method. Complications and risks, such as mousepart break off, have been reported to be lower with this technique.[19,20] In a study carried out by Ghirga et al.[21] in which the ticks were removed using fishing line thread, 71% of the ticks were completely detached, while mousepart was broken off in 29%. Similarly, in our study, 72% of the ticks were detached as a whole, 16% were broken off, and 12 were detached as a whole, but there was a technical mistake in suture lassoing. In our study, stages of the ticks were found as a nymph in 17 ticks and adult in 76 ticks. When the correlations between tick stages and technical mistakes were examined, 47% of nymph ticks and 16% of adult tick were broken off. The difference was statistically significant. Given the size of nymph ticks, this was an expected result. On a study by Akin Belli et al.,[13] 31% of 80 nymph ticks were broken off. We attribute the difference of our study to the different techniques used. In conclusion, the results of this study suggest that when appropriately and correctly used, both suture lassoing and tweezers are effective in tick removal. Tick removal should be primarily performed by healthcare professionals. The rate of technical mistakes is significantly lower in ticks detached by healthcare professionals. However, since tick should be removed as soon as possible when noticed, we think that the training of the public on this issue is also important.

Acknowledgement We would like to thank the academic personnel of Kahramanmaras Sutcu Imam University Hospital for their assistance. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.R.Ş., A.M.T., E.K.; Design: A.R.Ş, E.K.; Supervision: A.R.Ş., A.M.T.; Fundings: A.R.Ş.; Materials: A.R.Ş., E.K.; Data: A.R.Ş., H.H; Analysis: A.R.Ş., A.M.T.; Literature search: A.R.Ş, E.K; Writing: A.R.Ş.; Critical revision: A.R.Ş., A.M.T., E.K. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

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Şahin et al. Evaluation and comparison of tick detachment techniques and technical mistakes made during tick removal

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Kene çıkartım tekniklerinin değerlendirilmesi ve karşılaştırılması ile kene çıkarma sırasında yapılan teknik hatalar Dr. Ahmet Rıza Şahin,1 Dr. Hakan Hakkoymaz,2 Dr. Ali Muhittin Taşdoğan,3 Dr. Ekrem Kireçci4 Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, Kahramanmaraş Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Kahramanmaraş 3 Hasan Kalyoncu Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Gaziantep 4 Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi, Tıbbi Mikrobiyoloji Anabilim Dalı, Kahramanmaraş 1 2

AMAÇ: Keneler insan ve hayvanların önemli ektoparazitleridir. Keneler insanlara hastalığa neden olan patojenler bulaştırabilir. Kene teması KırımKongo Kanamalı Ateşi dahil olmak üzere çeşitli viral ve bakteriyel enfeksiyonlara yol açabilir. Kenelerin uygun yöntemlerle zamanında çıkarılması hastalık bulaşımının önlenmesi için önemlidir. Kene çıkartım teknikleri hastalığın oluşmasında etkili olabileceği için incelemeye değer bulunmuştur. Çalışmamızda bu tekniklerden ikisi olan kementle çıkarma ve tweezers yöntemlerini değerlendirmek, iki yöntemi karşılaştırmak ve bu yöntemlerle yapılan hataları incelemek amaçlanmıştır. GEREÇ VE YÖNTEM: Bu çalışma ileriye yönelik bir kesitsel çalışma olarak tasarlandı, acil servise kene teması ile başvuran hastalarda sağlık profesyonelleri veya hastaların kendileri tarafından çıkarılan keneyle ilgili olgular yer aldı. Keneler büyüme periyodlarına göre larva, nimf ve yetişkin olarak kaydedildi. Kene çıkartım türleri ve çıkarmada yapılan hatalar kaydedildi. BULGULAR: Kenelerin çoğunluğu (%77.4) sağlık profesyonelleri tarafından, daha düşük bir oranda ise hastaların kendileri tarafından el ile çıkarılmıştı (%22.6). Yetmiş iki hastada (%77.4) herhangi bir hata bulunmadı, kene bir bütün olarak çıkarılmıştı, 15 hastada (%16.1) parçalanmış olarak çıkarılırken, 6 (%6.45) hastada ise kene bir bütün olarak çıkarılmış ancak sütürler yanlış bağlanmıştı. Teknik hatalara bağlı kene parçalanması en çok kişilerin kendi çıkardığı kenelerde görüldü. TARTIŞMA: Bu çalışmanın sonuçları uygun ve doğru bir şekilde uygulandığında hem kement atma hem de tweezers tekniklerinin kene çıkarmada etkili olduğunu göstermiştir. Bu konuda halkın farkındalığını artırma ve eğitim programları artırılmalıdır. Anahtar sözcükler: Kene; kene çıkarma; sütür kement tekniği; tweezers tekniği. Ulus Travma Acil Cerrahi Derg 2020;26(3):405-410

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doi: 10.14744/tjtes.2020.59680

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ORIGIN A L A R T IC L E

Emergency surgery in geriatrics: A retrospective evaluation in a single center Özlem Sezen, M.D.,

Banu Çevik, M.D.

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

ABSTRACT BACKGROUND: As life expectancy increases in humans, surgical procedures applied to the elderly people are also increasing in parallel with the developments in surgery and postoperative care. A significant number of studies investigating the morbidity-mortality of geriatric patients are related to patients who are undergoing emergency operations. The present study aims to investigate the factors affecting mortality and morbidity after emergency surgery in elderly people. METHODS: The data of 200 patients aged 65 years and over who were operated under emergency conditions in the University of Health Sciences Kartal Dr. Lütfi Kırdar Training and Research Hospital between January and December 2018 were evaluated retrospectively. RESULTS: Patient’s demographic information, including age, gender, ASA physical status, comorbidities, functional dependency or non-dependency of patients, types of operation, anesthesia technique, duration of operation, intraoperative blood transfusion, the changes of hematocrit levels (during the perioperative period), the outcome after surgery (intensive care admission or ward transfer), were recorded. The risk prediction of short-term mortality has been estimated using CCI and APACHE II scoring systems. CONCLUSION: The mean age of the patients was 74.8±6.7 and the number of females (n=134, 67%) outweighed the males. Higher ASA physical status scores, dependent living conditions, long operation time, general anesthesia, intraoperative blood transfusion, low Htc values (<25%), high APACHE II scores and lower scores of 10-years survival by CCI were the factors that affected the acceptance into ICU. Keywords: Elderly; emergency; geriatric surgery; intensive care unit.

INTRODUCTION The proportion of elderly people is gradually increasing in the global population and the number of people aged over 60 years is expected to reach a number between 900 million to 2 billion by 2050.[1] The aged patients usually have many complex health problems, so during their long-life period, they often require immediate care or surgical interventions due to the developing complications as a consequence of the multiple underlying diseases. In parallel to the advances in modern surgery in all age groups, the number of elderly patients undergoing surgical interventions rises gradually. Concerning emergency surgeries, these patients are usually under-eval-

uated before the procedure because of the limited time for preoperative assessment. This may result in a worse outcome compared to the elective surgical procedures employed in the same age group.[2] Due to the lack of universally accepted risk prediction scores, the risk estimation in these patients is usually problematic. In a comparative study, the prevalence of mortality has been demonstrated in a wide range of 52–85% by six different screening instruments. The Vulnerable Elderly Survey (VES13) has been reported as the most accurate tool for risk assessment.[3] Acute Physiology and Chronic Health Evaluation [APACHE II] had a sensitivity of 96% in postoperative

Cite this article as: Sezen Ö, Çevik B. Emergency surgery in geriatrics: A retrospective evaluation in a single center. Ulus Travma Acil Cerrahi Derg 2020;26:411-417 Address for correspondence: Özlem Sezen, M.D. SBÜ Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Anesteziyoloji ve Reanimasyon Kliniği, İstanbul, Turkey Tel: +90 216 - 441 39 00 E-mail: drozlemsezen@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):411-417 DOI: 10.14744/tjtes.2020.90914 Submitted: 18.07.2019 Accepted: 29.04.2020 Online: 13.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Sezen et al. Emergency surgery in geriatrics: A retrospective evaluation in a single center

Our hospital is one of the main referral university-affiliated training hospitals, so a large proportion of the patients are admitted to the hospital for many advanced surgical procedures. In this study, we aimed to describe the clinical properties of the patients over 65 years old who underwent an emergency surgical intervention and discussed the factors affecting the postoperative outcomes in an anesthetic perspective.

MATERIALS AND METHODS This 680-bed-hospital is a tertiary health care center having two emergency operation rooms (OR) and a 32-bed-tertiary intensive care unit (ICU) working for 24 uninterrupted hours under the Department of Anesthesiology and Reanimation. After obtaining institutional Ethics Committee approval [2018/514/144/4] and informed consent from all patients, patients ≥65 years old that underwent an emergency surgical intervention between January and December 2018 were recruited in this study. This study was conducted according to the ethical principles outlined in the Declaration of Helsinki and guideline for the Good Clinical Practice (GCP).

Data Collection First, we reviewed the registry records of the operation rooms for finding the patients ≥65 years old. After that, the patient’s characteristics were extracted from the clinical registry in the hospital electronic database. Perioperative anesthetic management was recorded from the anesthesia charts of each patient. Patient’s demographics, including age, gender, ASA physical status, comorbidities, functional dependency or non-dependency of patients, types of operation, anesthesia technique, duration of operation, intraoperative blood transfusion, the changes of hematocrit levels (during the perioperative period), the outcome after surgery (intensive care admission or ward transfer), were recorded. The risk prediction of short-term mortality using CCI and APACHE II scoring system was estimated. The 412

main goal of this study was to evaluate these data and determine the factors affecting the outcome of the patients.

Statistical Analyses Data were analyzed using GraphPad Prism 7. In the study data, descriptive statistical parameters (mean, standard deviation, minimum and maximum value) were compared in binary groups using Student’s t-test, and in multiple comparisons, one-way ANOVA and Tukey post-test were used. The statistical significance levels were considered as ns: not significant, *p<0.05, **p<0.01, ***p<0.001, and ****p<0.0001.

RESULTS A total of 200 patients [134 females (67%), 66 males (33%) (9% of overall emergency surgical procedures] were included in this study. The patients were between 65–92 years (mean age, 74.8±6.7 years).

Patients’ Characteristics Patients were divided into three groups as 65≤years<75 (Group 1), 75≤years<85 (Group 2), and over 85 years (Group 3).The ICU admission after surgical procedure was significantly higher in patients over 85 years old (p=0.005). The rate of female and male patients admitted to ICU was similar to 40.3 and 37.9%, respectively (p=0.743). The mortality rates in patients were 14.8, 18.8, 35.7% in Groups 1,2, and 3, respectively (p=0.142). Age alone was not a significant factor in mortality. The mortality rates were also similar in both genders (17.9% in female, 16.7% in male; p=0.828). A higher ASA physical status was associated with a significant increase in ICU admission (p=0.003) and a higher mortality rate (p=0.019) (Fig. 1). The majority of the patients had more than one systemic comorbidity and parallel to the increase of additional systemic problems, ICU admission and mortality rates were gradually increased (Table 1). The living condition was expressed as an important factor affecting the outcome of elderly patients. Forty patients were nursing home patients who represented a significantly high percentage of ICU admission (p<0.001) and mortality rate (p<0.0001). 60

40 30

30.4% 24.1%

20

11.6%

10 0

ASA II ASA III

50.6%

50

%

mortality prediction, but it has been suggested that this tool was time-sparing during daily practice and usually used for the clinical researches.[4] Charlson Comorbidity Index (CCI) has been used for the prediction of preoperative outcomes after surgical procedures.[5] A modified version of the Canadian Study of Health and Aging Clinical Frailty Scale has been constructed to investigate the effects of frailty on infection outcomes and mortality for emergency patients aged 60 and older.[6] Although many other scoring systems have been introduced by the clinicians in different countries, these tools have limited specificity in the geriatric population.[7] The anesthesia consultation is mainly based on the American Society of Anesthesiologists (ASA) physical status classification, which is an easy tool for risk prediction in surgical patients. The estimated rate of mortality in patients aged 70 and older with ASA IV physical status has been reported up to 56.8%. [8] However, these results may show variations between the observers as a result of the subjective characteristics.

ICU admission

Mortality

Figure 1. The ASA, ICU admission and mortality relationship. ICU: Intensive care unit; ASA: American Society of Anesthesiologists.

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Sezen et al. Emergency surgery in geriatrics: A retrospective evaluation in a single center

Table 1. The distribution of the data related to the number of systemic diseases and the outcome of the patients Variables

0–1 2 3 4 p

Number of the patients, n (%)

40 (20)

ICU admission*

7.5±4.2 40.0±4.7 60.5±7.5 85.7±14.3 <0.0001**

Mortality rate*

0.0±0.0

*

110 (55)

43 (21.5)

12. 7±3.2

34.9±7.4

7 (3.5)

85.7±14.3

<0.0001**

Data are expressed as mean percentage ± SEM, **statistically highly significant. ICU: Intensive care unit.

Table 2. The ICU admission and mortality rates according to the duration of operation Variables

DO ≤60 min

60<DO≤120 min

120<DO≤180 min

180 min<DO

p –

The number of patients, n (%)

71 (35.5)

61 (30.5)

48 (24)

20 (10)

ICU admission*

11.3±3.8

34.4±6.1

68.8±6.7

85.0±8.2 <0.0001**

Mortality*

4.2±2.4

13.1±4.4

30.0±10.5

37.5±7.1 <0.0001

Data are expressed as mean percentage ± SEM, **statistically highly significant. ICU: Intensive care unit; DO: Duration of operation.

*

Surgical Characteristics and the Types of Anesthesia The distribution of surgical interventions was as follows; general surgery (110 patients; 55%), neurosurgical procedures (51 patients; 25.5%), orthopedic surgeries (30 patients; 15%) and urologic interventions (nine patients; 4.5%). The duration of operation (DO) was evaluated in four groups as DO≤60 minutes (min), 60 min<DO≤120 min, 120min <DO≤180 min, 180 min<DO. Longer surgical durations were found to be associated with higher ICU admission and mortality rates (Table 2). The types of anesthesia administered were general anesthesia (74%), regional (15%) and sedo-analgesia (11%) and the patients employing general anesthesia was indicated a high significance for admission to ICU in the postoperative period (<0.0001). Elderly patients undergoing general anesthesia mostly required critical care management (Fig. 2). The mortality rate was found significantly high in patients undergoing general anesthesia (21.2%) compared to regional (3.3%) and sedo-analgesia (7.1%) techniques (p=<0.0357).

Hematocrit Measurements The hematocrit (Htc) levels of the patients were divided into three groups as patients with Htc<25%, 25%≤Htc<38% and 38%≤Htc. The patients with an Htc level lower than 25% were admitted to ICU more frequently than the other patients and mortality rates of these patients were significantly higher when compared to the patients with higher levels of the Htc (Table 4).

APACHE II and CCI as Outcome Predictors The patients were divided into three groups based on their APACHE II scores as APACHE II ≤10 (n=30), 10<APACHE

Sedoanalgsia (11%) Regional anesthesia (15%)

Blood and Blood Products Transfusion Out of 200 patients, 113 (56.5%) patients received a blood transfusion. Of these patients, 71.3% were admitted to ICU after surgery. The amount of transfusion was also significantly associated with the number of patients admitted to ICU (p<0.0001) (Table 3). As the amount of transfusion increased, the mortality rates of patients were significantly increased (<0.0001). In nontransfused patients, the mortality rate was 5.3%±2.1% but it gradually increased in patients who were transfused with 0<packs≤2 (20.5%±6.6%), 3 packs (33.3%±9.2%) and 4≤packs (57.1%±11.1%) of blood. Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

General anesthesia (74%)

Figure 2. The distribution of the types of anesthesia in patients admitted to intensive care unit.

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Sezen et al. Emergency surgery in geriatrics: A retrospective evaluation in a single center

Table 3. The number of blood and blood products transfusion-ICU admission relationship Number of patients

The package of blood and blood products

113

ICU admission (%)

0

39

SEM (±)

15.0

0<packs≤2

p

3.4 <0.0001*

64.1 7.8

27

3 packs

74.1

21

4≤packs

80.9 8.8

8.6

SEM: Standard error of the mean; *Statistically highly significant. ICU: Intensive care unit.

Table 4. The relation of the hematocrit levels with ICU admission and mortality rate Variables

Htc<25% 25%<Htc<38% 38%≤Htc

The number of patients (%)

12 (6)

p

145(72.5)

43(21.5)

45.5±4.2

14.0±5.4 0.0003**

41.7±14.9 18.8±3.3

7.0±3.9 0.0156***

ICU admission*

58.3±14.9

Mortality rate*

*Data are expressed as mean percentage ± SEM; **p<0.001, statistically highly significant; ***p<0.05, statistically significant. ICU: Intensive care unit.

Table 5. Data related to the CCI scores Variables Number of patients

A B C D E p 41

38

60

34

27

ICU admission*

82.9±6.0 47.4±8.2 38.3±6.3 8.8±4.9 3.7±3.7 <0.0001**

Mortality*

63.4±7.6 15.8±6.0 3.3±2.3 2.9±2.9 0.0±0.0 <0.0001**

*

Data are expressed as mean percentage ± SEM; **statistically highly significant. ICU: Intensive care unit; CCI: Charlson Comorbidity Index.

II≤20 (n=135) and 20<APACHE II (n=35). The statistical analysis of ICU admission of patients and APACHE II scores revealed that higher APACHE II scores were associated with higher rates of ICU admittance with a ratio of 10.0±5.6%, 32.6±4.1% and 91.2±4.9, respectively (p<0.0001).The mortality rates increased up to 70.6±7.9 % in patients with APACHE II scores higher than 20 (p<0.0001). In the analysis of CCI scores, patients were divided into five groups as CCI=0% (A), 0%<CCI≤10% (B), 10%<CCI≤25% (C), 25%<CCI≤75% (D), and 75%<CCI (E) (Table 5). In Pearson correlation analysis, APACHE II and CCI showed a moderate positive correlation (p=0.569, R2=0.324) with a prediction power of 32.4%.

DISCUSSION We presented a retrospective evaluation of the patients aged 65 years and older who underwent emergency surgery and described the short-term outcomes of these patients. Our results showed that advanced age was a predictive factor for ICU admission, but concerning mortality, the results were insignificant. High ASA physical status scores, having more than one systemic comorbidity, dependent living condition, prolonged operation duration, general anesthe414

sia administration, intraoperative blood transfusion, lower HTC levels (<25%), higher APACHE II scores and the low estimated 10-years survival by CCI scores were the factors affecting the ICU admission in patients over 65 years after an emergency surgical intervention. APACHE II and CCI scores showed a moderate correlation with the prediction of 32.4% for elderly patients. A recent study concerning a 15-year retrospective analysis of elderly people who underwent an emergency surgical procedure revealed that the complexity of surgical interventions has increased during the time and seemed to be a challenge in the future.[9] The ratio of emergency surgery shows variability between countries according to the characteristics of a healthcare institution, the clinicians trained in the subspecialty areas, the population density, and the geographic differences. Previously, the overall emergency general surgery rate has been reported as 8–26%.[10] The emergent interventions were accompanied by higher rates of mortality than elective procedures due to pre-existing systemic diseases and age-related physiological changes rather than the surgical procedure itself.[11] A recent study Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Sezen et al. Emergency surgery in geriatrics: A retrospective evaluation in a single center

has indicated that older patients had a ten-fold higher mortality rate after major emergency surgery when compared to younger patients.[12] The ratio of the geriatric surgical emergency intervention was 9% in our hospital, and the overall mortality was 18%. Age itself is an important risk factor for postoperative morbidity and mortality; the risk-adjusted surgical mortality rates have been increased almost by 2-folds in patients older than 75 years.[13] In a 30-day outcome study, the morbidity and the mortality rates of the patients older than 80 years have been reported as 51 and 7%, respectively.[14] In our study, admission to ICU was significantly higher in patients with advanced age (over 85 years), but mortality did not differ when compared to the other elderly critically ill surgical patients. It is important to investigate patient’s physiological condition, the severity of the pre-existing disease, nutritional status, the presence of dehydration, depression, and the evaluation of cognitive functions play important roles in the pre-anesthetic assessment process. General anesthesia may impair the pulmonary functions, increase the myocardial depression, induce hypothermia and worsen the cognitive functions. On the other hand, regional anesthesia has potential difficulties because of the anatomical changes in advanced ages.[15] Our results showed that the number of systemic comorbidities (means higher ASA physical status), prolonged duration of the operation and the general anesthesia technique significantly affected the ICU admission after emergency surgery in geriatric patients. Fraility has been discussed since the 1990s and many tools for prediction of the outcome have been introduced.[16] Functional dependency is a practical assessment of fraility in elderly patients and usually indicates an advanced symptom of fraility.[17] When a surgical intervention was scheduled for an elderly patient, long-term hospitalization, dependency, home care requirement, institutionalization and even death are the possible outcomes.[18] A previous report indicated that patients with functional dependency have higher 30-day mortality rates than independent patients after major general and vascular surgery.[19] The dependency of the patients was also found to be a significant factor on the ICU admission in our study. Anemia is a common symptom in the elderly population and when the surgical interventions become in question, anemia has a negative impact on postoperative outcome and mortality. The assessment and the treatment of underlying causes may require intravenous iron therapy, nutritional support or preoperative blood transfusion.[20] Our study indicated that the ICU admission increased by 4-folds (15.0 vs. 64.1%) approximately in patients who were treated with one to two packs of blood transfusion during the intraoperative period. Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

Although APACHE II is a widely used tool to measure the severity of diseases in patients admitted to ICU, it is recommended for risk stratification before emergency surgical interventions.[21] APACHE II scoring consists of the physiological variables, age and chronic health evaluation points together. Thus, high scores before the surgery may reflect the postoperative outcome and prediction of ICU admission. Our results indicated that the majority of patients have APACHE II scores between 10 and 20 (n=135) or more than 20 (n=35), resulting in significantly high ICU admission and mortality rates. The Charlson comorbidity index has been validated in medical settings, critically ill patients, trauma patients and the elective surgical patients and predicts ten-year mortality based on 22 conditions, including age, medical, infection, and oncologic history of the patient and the end-organ dysfunction along with age, and increased CCI has been shown to be correlated with the increased mortality in advanced ages.[22] In a recent study, CCI has been reported as an effective component of preoperative risk assessment and provided useful information about the outcomes of elderly patients having laparoscopic surgery for colon cancer.[23] On the other hand, the efficacy of this score in the emergency surgical settings has remained limited in the literature. Despite the lack of sufficient data, some studies suggested that CCI might be used to estimate the morbidity and mortality in emergency surgical patients. [24] According to our results, patients with a 10-year survival rate of less than 25% admitted to ICU more than the others and the mortality rates were significantly higher in this group of patients. Geriatric patients need special care and must be separated from other patient groups. Concerning emergency situations, this issue becomes even more important.[25] Our results represented the data of a well-equipped single university-affiliated tertiary hospital in which many advanced surgical procedures have been conducted. Thus, these results cannot be applied to the entire population in our country. Also, hospital variability may result in different outcomes. Data were obtained retrospectively, which might cause a bias in data. The distribution of age groups was not similar, so the results may not be used in a similar aged-specified patient population. Our data did not include all postoperative complications, which might extend the duration of stay in the hospital. However, this was not the point of the study; we only focused on the outcomes after surgery and the early ICU mortality. The patients were not evaluated according to the degree of dependency, preoperative cognitive function and nutritional status. These issues may be the subjects of further clinical trials. Elderly patients requiring an emergency surgical operation is a double-edged sword in need of a special medical approach. Age itself is not a risk factor for the outcomes after surgery, 415


Sezen et al. Emergency surgery in geriatrics: A retrospective evaluation in a single center

but the general physical status of the patients and accompanying systemic dysfunctions have become more important for these patients. The lack of worldwide risk assessment scores and recommendations in this population arise necessities for further clinical trials in larger elderly populations. One of the more important points of the medical approach in these patients is to avoid futile treatments, and patient-centered care must be focused. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: Ö.S., B.Ç.; Design: Ö.S., B.Ç.; Supervision: Ö.S., B.Ç.; Fundings: Ö.S., B.Ç.; Materials: Ö.S.; Data: Ö.S.; Analysis: Ö.S., B.Ç.; Literature search: Ö.S., B.Ç.; Writing: Ö.S., B.Ç.; Critical revision: Ö.S., B.Ç. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

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Sezen et al. Emergency surgery in geriatrics: A retrospective evaluation in a single center

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Geriatrik hastada acil cerrahi: Tek merkezde geriye dönük değerlendirme Dr. Özlem Sezen, Dr. Banu Çevik Sağlık Bilimleri Üniversitesi Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Anesteziyoloji ve Reanimasyon Kliniği, İstanbul

AMAÇ: İnsanlarda yaşam beklentisi arttıkça, yaşlı insanlara uygulanan cerrahi prosedürler cerrahi ve ameliyat sonrası bakımdaki gelişmelere paralel olarak artmaktadır. Geriatrik hastaların morbidite-mortalitesini araştıran önemli sayıda çalışma acil ameliyat geçirenlerle ilgilidir. Bu çalışmanın amacı yaşlılarda acil cerrahi sonrası mortalite ve morbiditeyi etkileyen faktörleri araştırmaktır. GEREÇ VE YÖNTEM: Ocak–Aralık 2018 tarihleri arasında Sağlık Bilimleri Üniversitesi Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi’nde acil şartlarda ameliyat edilen 65 yaş ve üstü 200 hastanın verileri geriye dönük olarak değerlendirildi. BULGULAR: Hastaların demografik özellikleri yaş, cinsiyet, ASA fiziksel durumları, komorbiditeleri, fonksiyonel olarak bağımlı olup olmadıkları, ameliyat tipleri, anestezi tekniği, ameliyat süresi, intraoperatif kan transfüzyonu, hematokrit düzeyindeki değişiklikler (perioperatif dönemde) cerrahi sonrası sonuç (yoğun bakım ya da servise transfer) kaydedildi. Kısa vadeli ölümlerin risk tahmini, Charlson Comorbidity İndeks (CCİ) ve APACHE II puanlama sistemleri kullanılarak tahmin edildi. TARTIŞMA: Hastaların yaş ortalaması 74.8±6.7 idi ve kadın sayısı (n=134, %67) erkeklerden daha yüksekti. Yüksek ASA fiziksel durum skorları, bağımlı yaşam koşulları, uzun ameliyat süresi, genel anestezi, intraoperatif kan transfüzyonu, düşük Htc değerleri (<%25), yüksek APACHE II skorları ve 10 yıllık sağ kalım skorlarının CCİ’ye göre daha düşük olması yoğun bakım ünitesine kabulü etkileyen faktörlerdir. Anahtar sözcükler: Acil; geriatrik cerrahi; yaşlı hasta; yoğun bakım ünitesi. Ulus Travma Acil Cerrahi Derg 2020;26(3):411-417

doi: 10.14744/tjtes.2020.90914

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ORIGIN A L A R T IC L E

Decompressive craniectomy in traumatic brain injury: Transcranial Doppler sonography used as a guide Ramazan Sarı, M.D.,1 Fatih Han Bölükbaşı, M.D.,2 Eylem Burcu Kahraman Özlü, M.D.,1 Nejat Işık, M.D.,3 Melek Güra Çelik, M.D.,4 İlhan Elmacı, M.D.1 1

Department of Neurosurgery, Acıbadem Maslak Hospital, İstanbul-Turkey

2

Department of Neurosurgery, Rumeli University Faculty of Health Sciences, İstanbul-Turkey

3

Department of Neurosurgery, İstanbul Medeniyet Universitiy, Göztepe Training and Research Hospital, İstanbul-Turkey

4

Department of Anesthesia and Reanimation, İstanbul Medeniyet Universitiy, Göztepe Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: Decompressive craniectomy (DC) is performed in the management of intracranial hyper-tension after traumatic brain injury (TBI). This study aims to investigate the effects of transcranial Dop-pler ultrasonography (TCD) measurements on the indication of decompressive surgery. METHODS: Sixteen TBI patients with a Glasgow Coma Score (GCS) <9 were included in this study. Intra-cranial pressure (ICP) monitoring and transcranial Doppler ultrasonography (TCD) measurements were recorded continuously. DC was performed according to the records of ICP and TCD. Glasgow Outcome Scale (GOS) scores were evaluated after three months. RESULTS: Mean age of the patients was 31.18±17.51; GCS ranged between three and 14 with a mean of 9.62±3.95. Mean GOS was 3.12±1.85. Craniectomy was performed in two patients (12.5%) and cra-niectomy and lobectomy together were performed in 14 (87.5%) of them. The decline in ICP (22.12±10.41, 22.62±7.35, 15.50±6.64) and pulsatility index (PI) (1.96±1.10, 1.64±0.75, 1.91±2.48) were strongly significant between days 3–5, and 1–5. The range of PI and Vmax values through five days did not present any significance. CONCLUSION: TCD, as a real-time monitor, may help for an early decision of surgical approach in the management of TBI patients. Keywords: Decompressive craniectomy; neurointensive care; transcranial Doppler ultrasonography; traumatic brain injury.

INTRODUCTION Traumatic brain injury causes brain edema and intracranial hypertension, which may lead to secondary brain insults. The Brain Trauma Foundation guidelines state that DC must be considered for the evacuation of a space-occupying lesion or in cases with diffuse brain swelling and intracranial hypertension due to intensive medical management.[1–5] DC is the removal of an area of the skull to augment the volume of the intracranial compartment. DC was first described by Kocher in the treatment of post-traumatic brain oedema in 1901. Even though the procedure is being performed in

rapidly relieving intracranial hypertension, there are no clear guidelines for indications and optimal timing of the DC.[6] Several retrospective and prospective studies suggested the efficacy of DC in decreasing ICP and improve the outcome in patients with refractory intracranial hypertension following TBI. Massive oedema and brain swelling are the clinical conditions that lead the therapy to DC. Compression of the brain, as well as the impairment in cerebral blood flow, are the adverse effects of intracranial hypertension.[3,5,6] ICP monitoring is the gold standard in TBI patients and PI of TCD sonography is correlated with ICP, the effects of ICP monitoring and TCD sonography to guide the medical and surgical treatment protocols are investigated in this study.

Cite this article as: Sarı R, Bölükbaşı FH, Kahraman Özlü EB, Işık N, Güra Çelik M, Elmacı İ. Decompressive craniectomy in traumatic brain injury: Transcranial Doppler sonography used as a guide. Ulus Travma Acil Cerrahi Derg 2020;26:418-424. Address for correspondence: Ramazan Sarı, M.D. Acıbadem Maslak Hastanesi, Beyin ve Sinir Cerrahisi Kliniği, İstanbul, Turkey Tel: +90 212 - 304 44 44 / 5648 E-mail: drramazan@windowslive.com Ulus Travma Acil Cerrahi Derg 2020;26(3):418-424 DOI: 10.14744/tjtes.2020.04640 Submitted: 27.09.2019 Accepted: 15.01.2020 Online: 15.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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MATERIALS AND METHODS After the institutional ethical committee approved and informed consents waived, 52 TBI patients treated aggressively in the neurointensive care unit of Ministry of Health Goztepe Training Hospital were prospectively reviewed. Of these 52 patients (post-resuscitation GCS <9 in the emergency department, unilateral or bilateral motor posturing and computed tomography (CT) scans defined according to Marshall Classification and the patients who receded to lower GCS in the following days), 16 patients with an intracranial mass lesion on the admission CT, an abnormality of intracranial hemodynamic or who needed DC despite the medical management protocol were included in this study.[7] Patients who died within five days of admission, who had organ failure or severe infection before admission were excluded from this study. The neurological and hemodynamic status of the patients was assessed and the patients were intubated and mechanical ventilation was performed consequently. The CT scans of the patients were performed according to the cerebral and hemodynamic status of the patients on the following days. The control of elevated ICP was considered according to the guidelines of the Brain Trauma Foundation. Once admitted to the intensive care unit, mean arterial pressure of 90 mmHg, CPP 60–70 mmHg, ICP <20 mmHg, central venous pressure 5–10 mmHg, SaO2 >95% and PaCO2 of 30–35 mmHg were targeted. The head of the patients was routinely elevated at 300 up to improve jugular venous return. Anticonvulsants were performed in case of seizures. Euvolemia, normothermia and normoglycemia were considered. Antibiotic therapy for the intracranial process was performed with vancomycin, according to the guidelines of the Local Committee of Infection. GOS of the patients were evaluated after three months. GOS 1–3 was evaluated as unfavourable and GOS 4–5 was evaluated as a favourable outcome. The elevation of ICP was managed in three steps, moving from one step to another if the ICP values remained constant.[8] Step 1- If ICP >20 mmHg, slight hyperventilation and targeting a PCO2 of 35 mmHg. Step 2- Mannitol 20% 0.5–1.0 g/kg performed with intermittent boluses watching for plasma osmolarity <320 mOsm/ kg. High doses of mannitol (1.4 g/kg) used when ICP >30–40 mmHg. CPP maintained at a minimum of 60 mmHg with fluid administration, vasopressors like dopamine or norepinephrine in cases of low arterial pressure values. Step 3- If ICP remained high, following CT scan, barbiturates and early decision for decompressive craniectomy were considered. Arterial blood pressure was monitored in all patients by radial artery catheter. A parenchymal catheter with a fiberoptic Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

tip transducer into the frontal region or an intraventricular catheter (Integra MPM-1) was placed. The ICP catheters were inserted for five days and the catheters were changed if a longer period was required. ICP was measured continuously in software data. CPP was calculated from the difference between mean arterial pressure and ICP. Daily TCD mean flow velocity measurements of MCA were made by bilaterally and continuously. The TCD measurements were conducted transtemporally using a traditional 2 MHz transducer (DWL). The depth and angle of insonation, giving the highest mean flow velocity were chosen. Pathological PI values were considered as PI >1.0. The PI was calculated according to the Gosling index, from the difference between end-systolic and diastolic MCA velocities divided by the mean MCA velocity. For the statistical analysis, the first, third and fifth days measurements were considered. The statistical analysis was performed in SPSS 15.0 for Windows for data processing and analysis. The definitive analysis was used for mean, standard deviation, minimum and maximum variables. Pearson’s Correlation Analysis® for correlations, paired samples t-test for the differences between days was used. Simple Linear Regression analysis was used to achieve the effects of ICP upon PI. The statistical significance of the correlation between the investigated quantitative variables was achieved by the p level and the significance level was recorded as p<0.05.

RESULTS In 18 months, 16 TBI patients who had undergone decompressive craniectomy were investigated. The clinical data of the patients are summarized in Table 1. The mean age of the patients was 31.18±17.51, three of them (18.8%) were woman. GCS ranged between 3 and 14 with a mean of 9.62±3.95. Mean GOS was 3.12±1.85 with a median value of 4. Craniectomy was performed to two patients (12.5%) and craniectomy and lobectomy together were performed to 14 (87.5%) of them. The intracranial hemodynamic parameters were followed for five days, and 1st, 3rd, 5th days were evaluated. The deTable 1. Clinical data of the total group and decompressive surgery patients

Total DC (n=52) (n=16)

Traumatic subarachnoid haematoma

19

3

Contusional haematoma

11

7

Diffuse oedema

7

2

Epidural haematoma

6

1

Diffuse axonal injury

5

1

Subdural haematoma

4

2

DC: Decompressive craniactomy.

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Table 2. The mean ICP measurements on days 1, 3 and 5 Days

ICP

+p

Days 1–3

p

Days 1–5

++

p

Days 3–5

++

p

++

Mean±SD Median

1 22.12±10.41 19 0.007** 0.938

0.024* 0.001**

3 22.62±7.35 22.5 5 15.50±6.54 12 Friedman’s Test; ++Wilcoxon sign test; *p<0.05; **p<0.01. ICP: Intracranial pressure; SD: Stardard deviation.

+

Table 3. The correlation coefficients between ICP and PI and Vmax on days 1, 3 and 5 Days ICP-PI

r

p

Table 4. GOS evaluated in patients with DC and others DC

ICP-Vmax r

Mean±SD Median

Yes (n=16)

3.18±1.90

4

No (n=36)

2.59±1.51

2

*

p

p

1

0.105 0.699 -0.202 0.454

3

0.164 0.545 0.083 0.759

5

0.004 0.987 -0.520 0.039*

Spearman’s rho correlation coefficient *p<0.05. ICP: Intracranial pressure; PI: Pulsatility index; Vmax: Maximum flow velocity.

cline in ICP (22.12±10.41, 22.62±7.35, 15.50±6.64) and PI (1.96±1.10, 1.64±0.75, 1.91±2.48) values were strongly significant between days 3–5, and 1–5 (p<0.001) (Table 2). The range of PI and Vmax values through five days did not present any significance (1.96±1.10, 1.64±0.75 and 1.91±0.48) and (112.50±51.12, 99.93±40.15, 86.06±36.09), respectively. In the means of correlation, it was estimated as significant between ICP and Vmax on the fifth day (Table 3, Fig. 1). A relationship was also observed between GCS and GOS (Spearman’s correlation coefficient of 0.534, p<0.05) (Fig. 2).

0.227

Mann-Whitney U test. GOS: Glasgow outcome score; DC: Decompressive craniectomy.

*

The mean GOS of the 16 patients who had DC was higher than the 36 patients who had medical therapy, but no statistical significance was observed (Table 4).

DISCUSSION TBI is one of the most common causes of death. Marked elevation of ICP which causes cerebral ischemia and secondary insults is sometimes difficult to treat with medical managements alone. The adverse effects of intracranial hypertension are due to compression of the brain resulting with impairment in cerebral blood flow.[6] To prevent additional brain damage due to elevated ICP, neurosurgeons perform DC which improves clinical outcome.

30.00

5.00

25.00

4.00

20.00 GOS

ICP (mmHg)

GOS

3.00

15.00 2.00

10.00

1.00

5.00 0.00

50.00

100.00

150.00

200.00

Vmax (cm/sn)

Figure 1. Plots demonstrating the correlation between ICP and Vmax on day five. ICP: Intracranial pressure.

420

0.00

50.00

100.00

150.00

150.00

GCS

Figure 2. The correlation graphics of GCS and GOS of 16 patients. GCS: Glasgow Coma Score; GOS: Glasgow Outcome Scale.

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Sarı et al. Decompressive craniectomy in traumatic brain injury: TCD used as a guide

In taking the decision to operate, the risk of complications should be weighed with the potential benefits of the procedure. Factors that should be considered in patient selection are failed conservative strategies, early intervention of surgery (before 48 hours), before the development of features of brain herniation, GCS at least 8, age <50, no primary brain stem injury, abnormal pupillary findings, ICP <40 mmHg, midline shift <1 cm.[6] DC is the temporary removal of a portion of the skull for the relief of intractable intracranial hypertension.[9] High intracranial hypertension resulting from cerebral oedema, intracranial haemorrhage or space occupying hematoma may lead to secondary brain damage, herniation or death.[9] DC may minimize the ischemic damage by increasing the cerebral blood flow and tissue oxygenation. DC decreases the mortality and improve outcome especially when performed in the early phase. However, DC is still used as a salvage procedure after all options of ICP management are exhausted. Cochrane database reveals that DC must be performed in two completely different situations as follows: prophylactic decompression or primary decompressive craniectomy and therapeutic decompression or secondary decompressive craniectomy. The former decision is taken during the surgery, independent of ICP. The latter indication is to control high ICP supported by monitoring systems.[10] Close monitoring is the key in patients with TBI to make DC successful; however, this review concluded that there is no evidence to support the routine use of DC in TBI for refractory elevated ICP. In contrast to this, the American Brain Trauma Foundation guidelines mention bifrontal DC within 48 hours of injury as a treatment option in patients with elevated ICP.[9] The effects of the ICP and TCD measurements and their trends on the decision of craniectomy as a treatment option in individual cases are investigated in this study. As the presentation of ICP >20 mmHg was seen in TBI patients, and it was managed firstly with conservative treatment strategies as sedation, head up position, mannitol therapy, cerebrospinal fluid drainage, barbiturate coma. DC was handled as the last option for intractable intracranial hypertension except the ones who had surgery immediately for mass lesions. Of the 52 patients, seven contusion haematoma, three traumatic subarachnoid haematoma, one diffuse axonal injury and four epidural and subdural haematomas had DC (Table 1, Fig. 3). Elevated ICP is an important secondary insult in TBI patients. When a direct measurement of ICP is not possible, Middle cerebral artery (MCA) evaluation with TCD has been proposed as an alternative monitoring technique.[11–14] It has been demonstrated that waveforms obtained with TCD are affected by both increases of ICP or decreases of cerebral perfusion pressure (CPP). When ICP increases due to resistance of cerebral blood flow, diastolic flow velocity decreases, but PI increases. Diastolic velocities decrease more than systolic values which are directly correlated with PI, an Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

Figure 3. Preoperative and postoperative CT scans of a TBI patient.

indicator of disturbed cerebral perfusion.[15–21] Several studies have focused on the changes in MCA flow velocity measurements after head injuries and they reinforce the use of TCD together with multimodality monitoring to understand the patterns of perfusion, oxygenation and auto regulation.[15,22–24] In the observational study of Bellner et al.,[17] 81 patients with various diagnoses, including aneurismal subarachnoid haemorrhage, head injury and encephalitis, have had intraventricular catheter for ICP monitoring and multiple TCD measurements have been performed parallel to ICP recordings. Independent of the intracranial pathology, a significant correlation between PI and ICP and between flow velocity and ICP has been found. As a result of this study, PI measurements have given a good estimation of ICP in unconscious patients. Homburg et al.[11] have investigated 10 TBI patients and also found a positive correlation of PI and epidural pressures (r=0.82) and suggested that TCD may be a useful marker of ICP (9). Splavski et al.,[25] also, have concluded that measuring the MCA blood velocity after TBI has been proven a worthy tool to estimate ICP, as well as to evaluate early post-traumatic cerebral hemodynamic. Voulgaris et al. have inspected 37 patients with TBI. ICP monitoring and TCD examinations have been carried on subsequently during the first 48 hours. They have found that PI correlated significantly with CPP and ICP. When ICP values were below 20 mmHg, the correlation was not significant. When CPP has approached the lower auto regulatory limit, PI has started to increase rapidly. As CPP has decreased from 70 mmHg, an inverse correlation between CPP and PI has been obtained. PI has had a high predictive value for detecting low CPP and it has been a sensitive indicator for the need to monitor ICP.[26] 421


Sarı et al. Decompressive craniectomy in traumatic brain injury: TCD used as a guide

Martin et al. studied on 14 TBI patients investigating the TCD measurement changes through the treatment period. Distal vascular vasospasm was diagnosed with increases of mean velocities of middle cerebral artery and PI in the early period.[27] The similar changes are also observed in our patients. CT and TCD parameters guided the treatment protocol. In 62.5 % of the patients, surgery is performed in the first six hours. These patients had higher CPP and lower ICP values. There was no correlation observed between ICP and PI. The mean PI and ICP values were increased in the first day and declined in the following days (Table II) Vmax of MCA was correlated well with ICP in the fifth day, that is as ICP decreased with DC, MCA flow velocities improved (Table 3, Fig. 1). Early intervention of DC for TBI has resulted with good outcome in recently published case series. However, the term ‘early’ has not been defined. The ‘late’ group is defined as unmanageable ICP despite maximum medical treatment. It is concluded that patients presenting brain stem dysfunction upon their first neurological exam must be excluded as the procedure holds little hop effort improvement from this stage.[9] Guerra et al. have recommended DC to be moved to the first step in case of intractable intracranial hypertension. They have compared DC to hyperventilation, barbiturate coma and hypothermia and have concluded that surgery was safer with lower mortality and fewer complications.[28] Akyuz et al. also state that to obtain favourable outcomes in TBI, early decision making and patient selection are important. In a group of 36 TBI patients who had early intervention of bilateral DC, declined ICP values presented a reduced mortality rate and improved outcome, especially in GCS 6–8 patients.[29] In properly selected patients, a systematic approach for DC instituted within the first hours of trauma, had beneficial effects in the patient population of Rubiano et al. Early application of the DC protocol within less than 12 hours from injury, GCS less than nine, Marshall CT finding between III and IV and isolated TBI resulted with significantly less mortality than the conventional approach.[30] Eberle et al. performed DC to 106 patients and 43 of them had DC for decompression of intracranial hypertension as a rescue therapy in cases where herniation was expected. They concluded that DC had the potential to improve both survival and functional outcome in a selected group of patients who might have a chance of an improved outcome.[31] Munch et al. retrospectively analyzed 49 patients with GCS ≤8 and age >50 and who had early decompression within 4.5 hours. Rapid surgical decompression was performed to 63.3% of the patients, craniectomy had significantly decreased 422

midline shift and improved visibility of mesencephalic cisterns. Alterations in ICP and CPP were not significant and no beneficial effect on patient outcome was reported.[1,32] In the study of Howard et al. DC was performed to 152 patients and the surgery resulted with decreases in ICP and increases in CPP values. They propose that DC must be considered as early as possible to prevent secondary brain insults.[33] Bilateral DC was performed to 37 patients who had malign diffuse brain swelling after TBI. The ICP values significantly decreased after bone removal and a larger decrease were recorded after opening of the Dura mater. However, ICP was elevated after surgery but remained lower than the initial values and could be controlled with medical treatment. Of these 37 patients, 54.1% had a favourable outcome.[34] Patients with lower GCS have had low GOS. If a chance is used, it must be given immediately. Even though there is no significance observed, the patients who had DC had higher GOS. If it is foreseen that surgery might be performed with the algorithmic approach in the following hours or days, then it must be done early. Craniectomy is performed to 62.5% of the patients in the first six hours. The other 37.5% had higher GCS and CT findings did not demonstrate a necessity for emergent surgery (Table 4, Fig. 2). Complications of DC develop from path physiological changes in ICP, cerebrospinal fluid circulation and cerebral blood flow following the removal of skull. Contusion expansion, new intracranial hematoma may develop early after DC and subdural effusion, infectious problems and posttraumatic hydrocephalus are the delayed ones.[35,36] Although it has been shown that higher the decompression, higher the reduction in ICP, delayed complications, such as intracranial hematoma, contra lateral subdural effusion, infection and hydrocephalus, can be observed. DC reduces mortality, improves recovery, and reduces the duration in ICU. Outcome is also correlated with the timing of DC, age >50 and GCS <8 patients.[6] Cerebrospinal fluid fistula in four patients, infection in two patients and osteomyelitis observed in late period in one patient were the complications seen in our study group. These complications did not affect the GOS scores. Cranioplasty is performed in 8–12 weeks to 14 patients and two of them had cranioplasty late because of infection. In this study, TCD is used as a real-time monitor and the three steps therapy protocol was introduced step by step according to the measurements obtained. As van Santbrink et al. says, we have also concluded that an early insight in posttraumatic cerebral hemodynamic using TCD sonography is important to guide the management protocol and improve outcome.[37] According to the results of this study, PI may Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Sarı et al. Decompressive craniectomy in traumatic brain injury: TCD used as a guide

offer an insight about the post-traumatic cerebral hemodynamic, low cerebral blood flow resulting in low MCA flow velocity and high PI values.

Conclusion Transcranial Doppler ultrasonography is a noninvasive and reliable method to determine the intracranial pressure. If the TCD demonstrates an increased intracranial pressure, decompressive craniectomy must be performed as early as possible. The need for additional medications due to elevated ICP is lesser when decompressive craniotomy is performed. Lastly, early re-implantation of the bone flap will decrease the morbidity. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: R.S.; Design: R.S.; Supervision: İ.E.; Materials: F.H.B.; Data: F.H.B.; Analysis: F.H.B.; Literature search: E.B.K.Ö.; Writing: R.S.; Critical revision: İ.E., M.G.Ç. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

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9. Schirmer CM, Ackil AA Jr, Malek AM. Decompressive Craniectomy. Neurocrit Care 2008;8:456−70. 10. Sahuquillo J, Arikan F. Decompressive craniectomy for the treatment of refractory high intracranial pressure in traumatic brain injury. Cochrane Database Syst Rev 2006;(1):CD003983. 11. Homburg AM, Jakobsen M, Enevoldsen E. Transcranial Doppler recordings in raised intracranial pressure. Acta Neurol Scand 1993;87:488−93. 12. Moreno JA, Mesalles E, Gener J, Tomasa A, Ley A, Roca J, et al. Evaluating the outcome of severe head injury with transcranial Doppler ultra-

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31. Eberle BM, Schnüriger B, Inaba K, Gruen JP, Demetriades D, Belzberg H. Decompressive craniectomy: surgical control of traumatic intracranial hypertension may improve outcome. Injury 2010;41:894−8. 32. Rossi-Mossuti F, Fisch U, Schoettker P, Gugliotta M, Morard M, Schucht P, et al. Surgical Treatment of Severe Traumatic Brain Injury in Switzerland: Results from a Multicenter Study. J Neurol Surg A Cent Eur Neurosurg 2016;77:36−45. 33. Howard JL, Cipolle MD, Anderson M, Sabella V, Shollenberger D, Li

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36. Khalili H, Sadraei N, Niakan A, Ghaffarpasand F, Sadraei A. Role of Intracranial Pressure Monitoring in Management of Patients with Severe Traumatic Brain Injury: Results of a Large Level I Trauma Center in Southern Iran. World Neurosurg 2016;94:120−5. 37. van Santbrink H, Schouten JW, Steyerberg EW, Avezaat CJ, Maas AI. Serial transcranial Doppler measurements in traumatic brain injury with special focus on the early posttraumatic period. Acta Neurochir (Wien) 2002;144:1141−9.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Travmatik beyin hasarında dekompresif kraniektomi: Transkraniyal Doppler ultrasonografi yol gösterici olabilir mi? Dr. Ramazan Sarı,1 Dr. Fatih Han Bölükbaşı,2 Dr. Eylem Burcu Kahraman Özlü,1 Dr. Nejat Işık,3 Dr. Melek Güra Çelik,4 Dr. İlhan Elmacı1 Acıbadem Maslak Hastanesi, Beyin ve Sinir Cerrahisi Kliniği, İstanbul Rumeli Üniversitesi Sağlık Bilimleri Fakültesi, İstanbul 3 İstanbul Medeniyet Üniversitesi, Göztepe Eğitim ve Araştırma Hastanesi, Beyin ve Sinir Cerrahisi Kliniği, İstanbul 4 İstanbul Medeniyet Üniversitesi, Göztepe Eğitim ve Araştırma Hastanesi, Anestezi ve Reanimasyon Kliniği, İstanbul 1 2

AMAÇ: Dekompresif kraniektomi (DC), travmatik beyin hasarı (TBH) sonrası intrakraniyal hipertansiyon tedavisinde kullanılan etkin bir yöntemdir. Transkraniyal Doppler ultrasonografi (TCD) ölçümlerinin dekompresif cerrahi endikasyonundaki etkisini göstermektir. GEREÇ VE YÖNTEM: Çalışmaya Glasgow Koma Skoru (GCS) <9 olan 16 TBH hastası alındı. İntrakraniyal basınç (ICP) izleme ve TCD ölçümleri sürekli olarak kaydedildi. DC, ICP ve TCD kayıtlarına göre yapıldı. Glasgow Sonuç Ölçeği (GOS) skorları 3 ay sonra değerlendirildi. BULGULAR: Hastaların yaş ortalaması 31.18±17.51, GCS 3 ile 14 arasında değişmekte olup, ortalama 9.62±3.95 idi. Ortalama GOS 3.12±1.85 idi. İki hastaya (%12.5) kraniektomi, 14 hastaya (%87.5) kraniektomi ve lobektomi birlikte yapıldı. ICP’deki düşüş (22.12±10.41, 22.62±7.35, 15.50±6.64) ve pulsatilite indeksi (PI) (1.96±1.10, 1.64±0.75, 1.91±2.48) 3–5 ve 1–5 günleri arasında belirgin olarak anlamlıydı. Beş güne kadar olan PI ve Vmax değerleri arasında anlamlı bir fark bulunmamıştır. TARTIŞMA: TCD, gerçek zamanlı bir monitör olarak, TBH hastalarının tedavisinde cerrahi yaklaşımın erken kararına yardımcı olabilir. Anahtar sözcükler: Dekompresif kraniektomi; nöroyoğun bakım; transkraniyal Doppler ultrasonografi; travmatik beyin hasarı. Ulus Travma Acil Cerrahi Derg 2020;26(3):418-424

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doi: 10.14744/tjtes.2020.04640

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ORIGIN A L A R T IC L E

The role of trauma mechanism, fracture pattern and fixation technique on clinical outcomes and epiphyseal growth arrest in the surgical treatment of distal tibial epiphysiolysis Furkan Çağlayan Aslantaş, M.D.,1 Mustafa Yalın, M.D.,2 Mehmet Hakan İlter, M.D.,3 Alkan Bayrak, M.D.,3 Erdem Edipoğlu, M.D.,3 Bülent Tanrıverdi, M.D.,3 Altuğ Duramaz, M.D.,3 Mustafa Gökhan Bilgili, M.D.3 1

Department of Orthopedics and Traumatology, Ardahan State Hospital, Ardahan-Turkey

2

Department of Orthopedics and Traumatology, Elazığ Training and Research Hospital, Elazığ-Turkey

3

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

ABSTRACT BACKGROUND: Distal tibial epiphyseal fractures damage to epiphyseal growth plate. Epiphyseal growth arrest (EGA), reflex sympathetic dystrophy and ankle joint stiffness may also occur after distal tibial epiphyseal injury. This study aims to evaluate the role of trauma mechanism, fracture pattern and fixation technique on clinical outcomes and EGA in the surgically treated distal tibial epiphyseal fractures. METHODS: Twenty seven patients who underwent surgery for distal tibial epiphyseal fracture between the 2011 and 2017 were evaluated retrospectively. The effects of trauma mechanism, fixation technique, preoperative duration, fracture patterns on the clinical results and EGA were examined. AOFAS (The American Orthopedic Foot and Ankle Score) and MOXFQ (The Manchester-Oxford Foot Questionaire) were used for clinical evaluation. RESULTS: Twenty seven patients (17 male and 10 female) were included in this study. The most important complication of epiphyseal injury was the growth pause in eight patients. No statistically significant difference was observed concerning clinical scores and complications according to trauma mechanism, fixation techniques and fracture patterns (p>0.05). CONCLUSION: Regardless of the trauma mechanism, fracture pattern and the fixation material, an anatomical reduction should be obtained in distal tibial epiphyseal fractures to reduce complications and prevent the EGA. Keywords: Distal tibial epiphyseal fractures; epiphyseal growth arrest; fixation technique; fracture pattern.

INTRODUCTION Ankle fractures account for approximately 5% of all fractures in children and 15–20% of all epiphyseal injuries and are the most common epiphyseal injury in the lower extremity.[1–4] Ankle epiphyseal injuries are more common in males than females and tibia fractures are most common in eight to 15 years of age, and accompanying fibular fractures are most common between eight and 14 years.[5] Epiphyseal growth arrest (EGA), osteoarthritis, reflex sympathetic dystrophy, and

ankle joint stiffness may occur after distal tibial epiphyseal injury. The most important complication among these is the EGA. This complication is more frequent after Salter-Harris type 3 and 4 fractures and often causing limb length discrepancy and angular deformities of the ankle. In the literature, the patients treated with open reduction and internal fixation for Salter&Harris type 3 or 4 fracture have been shown to have an 11-fold lower risk of developing a growth problem than the patients treated with closed

Cite this article as: Aslantaş FÇ, Yalın M, İlter MH, Bayrak A, Edipoğlu E, Tanrıverdi B, et al. The role of trauma mechanism, fracture pattern and fixation technique on clinical outcomes and epiphyseal growth arrest in the surgical treatment of distal tibial epiphysiolysis. Ulus Travma Acil Cerrahi Derg 2020;26:425-430. Address for correspondence: Altuğ Duramaz, M.D. Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmataloji Kliniği, İstanbul, Turkey Tel: +90 212 - 414 71 71 E-mail: altug.duramaz@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(3):425-430 DOI: 10.14744/tjtes.2019.27354 Submitted: 10.04.2019 Accepted: 30.08.2019 Online: 13.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Aslantaş et al. Epiphyseal growth ar­rest in the distal tibial epiphysiolysis

reduction.[6] Limb length discrepancy is associated with the age of the patient and is usually between 1 and 2 cm.[7] The present study aims to evaluate the role of trauma mechanism, fracture pattern and fixation technique on clinical outcomes and epiphyseal growth arrest in the surgically treated distal tibial epiphyseal fractures. Our hypothesis is that K-wire fixation will be superior to clinical scores and EGA development compared to cannulated screw fixation.

MATERIALS AND METHODS This study was compiled from a retrospective review of the medical records of 46 surgically treated patients for distal tibial epiphyseal injury between the years 2011–2017 after the approval of local ethics committee (Bakırköy Dr. Sadi Konuk Education and Research Hospital Ethics Committee, protocol code: 2017/431, approval ID: 2017-18-31). A distal tibial epiphyseal injury requiring surgery, displacements greater than 2 mm, at least 1-year follow-up, and no accompanying injuries were the inclusion criteria. Open fractures, inadequate followup duration, and conservative treatment were excluded from this study. Twenty-seven patients (17 male and 10 female) who met the inclusion criteria were included in this study. The mean age was 11.9 years (between 5 and 17 years old). The effects of trauma mechanism, fixation technique, preoperative duration, fracture types (classification of Salter-Harris and Dias&Tachdjian) on the clinical results and EGA were examined. All patients were evaluated clinically and radiologically at postoperative 2nd week, 6th week, 3rd month and 6th month and then evaluated annually. AOFAS (The American Orthopedic Foot and Ankle Score) and MOXFQ (The Manchester-Oxford Foot Questionaire) were used for clinical evaluation. Radiological results, including EGA and fracture union, were evaluated by an independent senior orthopedic surgeon.

Surgical Technique and Postoperative Care All patients infused 30 mg/kg intravenous cefazoline sodium 30 min before surgery. All patients were operated under general anesthesia in the supine position. The closed reduction under fluoroscopic guidance and minimally invasive or percutaneous fixation which parallel to the physeal line was performed. K-wire between 1.8 mm and 2.5 mm was used in 11 patients, and HCCS (headless conical compression screw) with 2.5 mm diameter was used in 16 patients. The patients were followed for two weeks postoperatively with a below knee cast. Then, passive joint motion exercises were started by removing the cast. Patients were allowed to full weight bearing after radiographic fracture healing was demonstrated.

Statistical Analysis Descriptive statistics (average, standard deviation, minimum, median, maximum) were used to define continuous variables. The relationship between more than two continuous variables, such as fracture classifications which were not suitable for an independent and normal distribution was examined by the Kruskal Wallis test. The relationship between two 426

continuous variables, such as fibular fracture and trauma mechanism, which were not suitable for normal and normal distribution was investigated with the Mann-Whitney U test. Chi-Square (or Fisher Exact test where appropriate) was used to examine the relationship between categorical variables, such as EGA and fixation technique. Spearman’s rho correlation analysis was performed for the correlation of two continuous variables which do not conform to a normal distribution. The statistical significance level was determined as p<0.05. The analyses were performed using the MedCalc Statistical Software version 12.7.7 (MedCalc Software bvba, Ostend, Belgium; http://www.medcalc.org; 2013).

RESULTS The demographic characteristics of the patients are presented in Table 1. The duration of operation of the patients Table 1. Descriptive characteristics of the patients Age (year)

Mean±SD

Median (Min-Max)

11.9±3.2

13 (5–17)

Time to surgery

4.3±2.03

4 (1–8)

AOFAS score

86.04±9.8

85 (65–100)

MOXFQ Walking-Standing

0.23±0.1

0.21 (0.03–0.6)

MOXFQ Social interaction

0.16±0.1

0.18 (0–0.4)

MOXFQ Pain

0.18±0.1

0.15 (0–0.36)

n

%

Male

17

63

Female

10

37

Gender

Trauma mechanism

High energy

8

29.6

Low energy

19

70.4

Fixation method

K wire

11

40.7

Cannulated screw

16

59.3

Epiphysial growth arrest

No

19

70.4

Yes

8

29.6

Accompanying fibula fracture

No

17

63

Yes

10

37

Salter&Harris classification 2

8

29.6

3

14

51.9

4

5

18.5

AOFAS: The American Orthopedic Foot and Ankle Score; MOXFQ: The Manchester-Oxford Foot Questionaire; SD: Standard deviation; Min: Minimum; Max: Maximum.

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Aslantaş et al. Epiphyseal growth ar­rest in the distal tibial epiphysiolysis

Table 2. Functional evaluation and development of epiphyseal growth arrest according to fracture classification Salter&Harris classification

2

3

Mean±SD Median (Min-Max)

Mean±SD Median (Min-Max)

AOFAS

87.5±10.8

84.7±10.5

87 (67–98)

84.5 (65–100)

MOXFQ Walking–Standing

0.25±0.17

0.23±0.15

0.23 (0.03–0.6)

0.23 (0.07–0.6)

0.14±0.14

0.15±0.13

0.16 (0–0.31)

0.15 (0–0.37)

MOXFQ Social interaction MOXFQ Pain

4

p

Mean±SD Median (Min-Max) 87.4±6.6

0.808*

87 (80–97) 0.23±0.1

0.935*

0.17 (0.14–0.37) 0.23±0.14

0.489*

0.25 (0–0.4)

0.16±0.12 0.16±0.08 0.27±0.07 0.075*

0.12 (0.05–0.35)

0.15 (0–0.3)

n (%)

n (%)

n (%)

p

3 (37.5)

3 (37.5)

2 (25.0)

0.621**

PEE

SER

SI

p

Mean±SD Median (Min-Max)

Mean±SD Median (Min-Max)

Mean±SD Median (Min-Max)

Epiphyseal growth arrest Dias&Tachdijan classification AOFAS

0.3 (0.2–0.36)

86.1±5.9 89±11.9 86.4±9.9 0.588* 84 (79–98)

90 (67–100)

85 (65–100)

MOXFQ Walking–Standing 0.3±0.1 0.2±0.2 0.2±0.1 0.109* MOXFQ Social interaction MOXFQ Pain

0.3 (0.17–0.32)

0.1 (0.03–0.6)

0.2±0.1

0.1±0.1

0.2 (0–0.2)

0 (0–0.2)

0.2 (0.1–0.4) 0.2±0.1

0.097*

0.2 (0–0.4)

0.2±0.1 0.2±0.1 0.2±0.1 0.935*

0.2 (0.05–0.3)

0.1 (0.05–0.3)

n (%)

n (%)

n (%)

p

3 (37.5)

3 (37.5)

2 (25.0)

0.393**

Epiphyseal growth arrest

0.1 (0–0.4)

* Kruskal Wallis p, **Fisher’s Exact p. AOFAS: The American Orthopedic Foot and Ankle Score; MOXFQ: The Manchester-Oxford Foot Questionaire; PEE: Pronationeversion-external rotation; SER: Supination-external rotation; SI: Supination-inversion; SD: Standard deviation; Min: Minimum; Max: Maximum.

differed due to various reasons, such as additional medical conditions and edema and blister formation after trauma. Dias & Tachdjian and Salter Harris metods were used as fracture classification. There was no significant difference in AOFAS score, MOXFOQ score and EGA between subtypes of both fracture classification (Table 2). The most important complication of epiphyseal injury was the growth pause in eight patients. No statistically significant difference was observed concerning clinical scores and complications according to trauma mechanism (high-energy injury, such as traffic accident and falling from a height, low-energy injury, such as simple fall and buckling), fixation techniques (K-wire and HCCS) and fracture patterns (p>0.05) (Table 3).

DISCUSSION The most important finding of the present study is that difUlus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

ferent fixation techniques do not affect clinical scores and the development of EGA. Tibia distal epiphyseal injuries are the most common type of fracture in all epiphyseal injuries. [8] Epiphyseal injuries are more frequent than diaphyseal fractures.[9] Tibia distal epiphyseal injuries may lead to complications, such as damage to the epiphyseal growth due to the presence of the growth plate. The tibial epiphysial injury is often associated with fibula fractures. Cai et al.[10] reported that the presence of concomitant fibula fracture increased EGA risk for Salter-Harris type 3 and type 4. Contrary to this study, it was determined that the presence of fibula injury did not cause a significant effect on the AOFAS and MOXFQ scores or on the risk of EGA in our study. This finding can be explained by anatomic reduction and percutaneous fixation that was performed for all patients with fibula fractures. 427


Aslantaş et al. Epiphyseal growth ar­rest in the distal tibial epiphysiolysis

Table 3. Comparison of postoperative 1st year functional outcomes and epiphyseal growth arrest according to fixation technique. trauma mechanism and presence of fibula fracture Fixation technique AOFAS

K wire

Cannulated screw

Mean±SD Median (Min-Max)

Mean±SD Median (Min-Max)

84.4±11.4

87.2±8.7

84 (65–100)

MOXFQ Walking–Standing

0.23±0.13

Epiphyseal growth arrest

0.753*

0.21 (0.07–0.6)

0.17±0.14

0.16±0.13

0.25 (0–0.37)

MOXFQ Pain

0.512*

87.5 (67–100)

0.25±0.17 0.25 (0.03–0.6)

MOXFQ Social interaction

p

0.716*

0.18 (0–0.4)

0.17±0.09

0.19±0.11

0.577*

0.15 (0.05–0.3)

0.2 (0–0.36)

n (%)

n (%)

p

2 (25.0)

6 (75.0)

0.405**

Fibula fracture No Yes p AOFAS MOXFQ Walking–Standing MOXFQ Social interaction MOXFQ Pain

Mean±SD Mean±SD Median (Min-Max) Median (Min-Max) 85.8±9.9

86.4±10.06

85 (65–100)

1.00*

85 (68–100)

0.24±0.1

0.22±0.16

0.21 (0.07–0.6)

0.505*

0.23 (0.03–0.6)

0.17±0.13

0.16±0.15

0.18 (0–0.4)

0.863*

0.18 (0–0.37)

0.18±0.09

0.18±0.1

0.2 (0–0.36)

0.15 (0.05–0.35)

n (%)

n (%)

p

3 (37.5)

5 (62.5)

0.102**

High energy

Low energy

p

Epiphyseal growth arrest Trauma mechanism AOFAS MOXFQ Walking–Standing MOXFQ Social interaction MOXFQ Pain

0.980*

Mean±SD Mean±SD Median (Min-Max) Median (Min-Max) 82.4±11.9 82.5 (65–98) 0.29±0.16 0.28 (0.07–0.6) 0.24±0.12 0.25 (0–0.37) 0.23±0.09

87.6±8.6 0.238* 87 (67–100) 0.21±0.13

0.132*

0.17 (0.03–0.6) 0.13±0.13

0.058*

0.12 (0–0.4) 0.16±0.09

0.095*

0.25 (0.05–0.35)

n (%)

n (%)

p

3 (37.5)

5 (62.5)

0.658**

Epiphyseal growth arrest

0.15 (0–0.36)

*Mann-Whitney U, **Fisher’s Exact p. AOFAS: The American Orthopedic Foot and Ankle Score; MOXFQ: The Manchester-Oxford Foot Questionaire. SD: Standard deviation; Min: Minimum; Max: Maximum.

428

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Aslantaş et al. Epiphyseal growth ar­rest in the distal tibial epiphysiolysis

Some authors have suggested that the arrest of growth arise from epiphyseal trauma at the time of injury.[11] It has been reported in the literature that growth plate problems are more frequent after Salter-Harris type 3–4 injuries.[12,13] The most important complication of epiphyseal injury, EGA, was 29.6% (eight patients) in the present study. Although SalterHarris type 3 and 4 fractures were moderately worse than type 2 fractures in accordance with the literature, no statistically significant difference was observed concerning EGA in the present study. Dias and Tachdjian[14] noted that the most common type of injury was the supination inversion type injury. On the other hand, Rohmiller et al.[15] reported that there was a relationship between the injury mechanism and EGA and that they observed 35% EGA, especially after supination-external rotation injury. In the present study, the most common injury mechanism was supination-inversion and the rate of EGA in patients with supination-external rotation injury was 42%. No difference was observed between the Dias & Tachdjian fracture types concerning EGA rate. Taşkıran et al.[16] performed the first study that the AOFAS scoring system was used as a quantitative data in children with tibial distal growth plate fractures. The AOFAS score for their study was 86.6. In another study, Çiçekli et al.[17] used the AOFAS score and recorded an average AOFAS score of 96. In the present study, the mean AOFAS score was 86.04, in accordance with the literature. To our knowledge, this is the first study in the literature that has used the MOXFQ score in children with tibial distal growth plate fractures. In the MOXFQ scoring system, the results range from 0 to 1 and functional results are improved when approaching 0. The three parameters of this scoring system, walking/standing, pain, and social interaction, had mean values of 0.23, 0.18, 0.16, respectively in the present study. Although the pain of the operated extremity increased with movement and walking, the functional results were good. Also, no statistically significant difference was found between mean AOFAS and mean MOXFQ scores when the patients were grouped according to Dias & Tachdjian classification and Salter-Harris classification. In the present study, there were no statistically significant differences in the comparison of AOFAS and MOXFQ scores in eight patients diagnosed with epiphysiolysis after high-energy trauma and 19 patients diagnosed with the low-energy injury. Leary et al.[18] reported that high-energy trauma increased the risk of EGA compared to low-energy trauma or sports injuries. In the present study, there was no increase in the risk of EGA in high-energy trauma patients with no difference in clinical outcomes. Özkul et al. also reported that high-energy trauma did not increase the risk of EGA. We think that anatomic reduction has a positive effect on functional outcome even in cases of high energy injury. It was determined that preoperative hospitalization time did not affect the EGA risk. Also, no significant relationship was found between preoperative hospitalization time and AOFAS and MOXFQ scores. [19]

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Different types of implants have been used for fixation of epiphyseal fractures. In previous studies, K wires, tension band, metallic screws and bioabsorbable screws were used for fixation.[20–23] A biomechanical study showed that metallic screw fixation in the distal tibia significantly changed the intraarticular pressure in the ankle joint.[24] Cottalorda suggested an epiphyseal lag screw in the spongiform bone to provide anatomic reduction and better compression of the fracture line, stating that the reduction and compression were better with screws than with K wires.[25] Çicekli et al.[17] compared cannulated screws with headless cannulated screws in the treatment of distal tibial epiphyseal fractures but found no difference in clinical healing outcomes or complication rates. In the series where plain thin K-wires were used, there were less growth plate problems compared to the series made with other fixation materials.[16] In our patients, K wires or cannulated screws were used as the fixation material after anatomic reduction under the fluoroscopic guidance. In our study, a cannulated screw was preferred for anatomic fixation and compression of the fracture line in Salter-Harris Type 3 fractures. There was no statistically significant relationship between the type of fixation and clinical outcome and complication rate. This statistical determination refuted our hypothesis, which can be explained with that the patients are operated on in a short time and soft tissue problems are reduced. Thus, the fractures can be easily reduced with closed anatomic reduction maneuver. Also, K-wire is theoretically less damaging to the physeal region due to its smaller diameter and its application without drilling. This has a positive effect on clinical scores and may reduce the risk of EGA. In our study, it was thought that there was no significant difference in clinical scores and EGA due to the close diameters of K-wire and HCCS used as fixation material. Small the number of patients, retrospective design and short follow-up time are the limitations of the present study. In conclusion, EGA and clinical scores did not differ significantly concerning trauma mechanism, fracture pattern and fixation material in our study. Therefore, regardless of the trauma mechanism, fracture pattern, and fixation material, anatomic reduction is critical in distal tibial epiphyseal fractures to reduce complications and prevent EGA. Different fixation techniques may not affect clinical scores and the development of EGA. Ethics Committee Approval: Bakırköy Dr. Sadi Konuk Education and Research Hospital Ethics Committee, protocol code: 2017/431, approval ID: 2017-18-31. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: F.Ç.A., M.G.B.; Design: F.Ç.A., M.G.B; Supervision: M.Y., M.H.İ.; Fundings: M.Y, B.T., M.H.İ.; Materials: F.Ç.A, B.T, E.E.; Data: F.Ç.A, M.H.İ.; Analysis: A.B., A.D.; Literature search: F.Ç.A, A.B., A.D.; Writing: F.Ç.A, A.D.; Critical revision: A.D., M.G.B. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. 429


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14. Dias LS, Tachdjian MO. Physeal injuries of the ankle in children: classification. Clin Orthop Relat Res 1978;:230–3.

1. Landin LA, Danielsson LG. Children’s ankle fractures. Classification and epidemiology. Acta Orthop Scand 1983;54:634–40. 2. Peterson HA, Madhok R, Benson JT, Ilstrup DM, Melton LJ 3rd. Physeal fractures: Part 1. Epidemiology in Olmsted County, Minnesota, 1979-1988. J Pediatr Orthop 1994;14:423–30. 3. Peterson CA, Peterson HA. Analysis of the incidence of injuries to the epiphyseal growth plate. J Trauma 1972;12:275–81. 4. Mizuta T, Benson WM, Foster BK, Paterson DC, Morris LL. Statistical analysis of the incidence of physeal injuries. J Pediatr Orthop 1987;7:518–23. 5. Spiegel PG, Cooperman DR, Laros GS. Epiphyseal fractures of the distal ends of the tibia and fibula. A retrospective study of two hundred and thirty-seven cases in children. J Bone Joint Surg Am 1978;60:1046–50. 6. Kling TF Jr, Bright RW, Hensinger RN. Distal tibial physeal fractures in children that may require open reduction. J Bone Joint Surg Am 1984;66:647–57. 7. Caterini R, Farsetti P, Ippolito E. Long-term followup of physeal injury to the ankle. Foot Ankle 1991;11:372–83. 8. Hynes D, O’Brien T. Growth disturbance lines after injury of the distal tibial physis. Their significance in prognosis. J Bone Joint Surg Br 1988;70:231–3. 9. Oeppen RS, Connolly SA, Bencardino JT, Jaramillo D. Acute injury of the articular cartilage and subchondral bone: a common but unrecognized lesion in the immature knee. AJR Am J Roentgenol 2004;182:111–7. 10. Cai H, Wang Z, Cai H. Surgical indications for distal tibial epiphyseal fractures in children. Orthopedics 2015;38:e189–95. 11. Dugan G, Herndon WA, McGuire R. Distal tibial physeal injuries in children: a different treatment concept. J Orthop Trauma 1987;1:63–7. 12. Bellido PC, Wadhwani J. Retrospective observational study comparing treatment options in salter and harris type III epiphyseal fractures. Int J Orth Scie 2017;3:188−90. 13. de Sanctis N, Della Corte S, Pempinello C. Distal tibial and fibular epiphyseal fractures in children: prognostic criteria and long-term results in 158 patients. J Pediatr Orthop B 2000;9:40–4.

15. Rohmiller MT, Gaynor TP, Pawelek J, Mubarak SJ. Salter-Harris I and II fractures of the distal tibia: does mechanism of injury relate to premature physeal closure?. J Pediatr Orthop 2006;26:322–8. 16. Taşkıran MC, Turgut A, Kalenderer O, Ağuş H. Clinical and radiological results in distal tibial physeal injuries. [Article in Turkish]. Ulus Travma Acil Cerrahi Derg 2012;18:495–500. 17. Çiçekli Ö, Özdemir G, Uysal M, Biçici V, Bingöl İ. Percutaneous cannulated screw fixation for pediatric epiphyseal ankle fractures. Springerplus 2016;5:1925. 18. Leary JT, Handling M, Talerico M, Yong L, Bowe JA. Physeal fractures of the distal tibia: predictive factors of premature physeal closure and growth arrest. J Pediatr Orthop 2009;29:356–61. 19. Özkul B, Saygılı MS, Çetinkaya E, Arslanoğlu F, Bayhan IA, Demir B, et al. Angular deformity development after the distal tibial physeal fractures. Acta Orthop Belg 2016;82:814−20. 20. Wuerz TH, Gurd DP. Pediatric physeal ankle fracture. J Am Acad Orthop Surg 2013;21:234–44. 21. Podeszwa DA, Wilson PL, Holland AR, Copley LA. Comparison of bioabsorbable versus metallic implant fixation for physeal and epiphyseal fractures of the distal tibia. J Pediatr Orthop 2008;28:859–63. 22. Castellani C, Riedl G, Eberl R, Grechenig S, Weinberg AM. Transitional fractures of the distal tibia: a minimal access approach for osteosynthesis. J Trauma 2009;67:1371–5. 23. Sankar B, Lee NY, Henman PD. Periosteal tension band fixation of a pronation external rotation type fracture of the ankle in a child. Orthopedics 2013;36:444–8. 24. Charlton M, Costello R, Mooney JF 3rd, Podeszwa DA. Ankle joint biomechanics following transepiphyseal screw fixation of the distal tibia. J Pediatr Orthop 2005;25:635–40. 25. Cottalorda J, Béranger V, Louahem D, Camilleri JP, Launay F, Diméglio A, et al. Salter-Harris Type III and IV medial malleolar fractures: growth arrest: is it a fate? A retrospective study of 48 cases with open reduction. J Pediatr Orthop 2008;28:652−5.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Distal tibial epifizyolizin cerrahi tedavisinde travma mekanizması, kırık paterni ve fiksasyon tekniğinin klinik sonuçlar ve epifiz büyümesinin durması üzerine etkisi Dr. Furkan Çağlayan Aslantaş,1 Dr. Mustafa Yalın,2 Dr. Mehmet Hakan İlter,3 Dr. Alkan Bayrak,3 Dr. Erdem Edipoğlu,3 Dr. Bülent Tanrıverdi,3 Dr. Altuğ Duramaz,3 Dr. Mustafa Gökhan Bilgili3 1 2 3

Ardahan Devlet Hastanesi, Ortopedi ve Travmataloji Kliniği, Ardahan Elazığ Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmataloji Kliniği, Elazığ Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmataloji Kliniği, İstanbul

AMAÇ: Distal tibial epifiz kırıkları, epifiz büyüme plağına zarar verir. Distal tibial epifiz yaralanmasından sonra epifiz büyümesi durması (EBD), osteoartrit, refleks sempatik distrofi ve ayak bileği eklemi sertliği de görülebilir. Bu çalışmanın amacı, cerrahi olarak tedavi edilen distal tibial epifiz kırıklarında travma mekanizması, kırık paterni ve fiksasyon tekniğinin klinik sonuçlar ve EBD üzerindeki etkisini değerlendirmektir. GEREÇ VE YÖNTEM: 2011–2017 yılları arasında distal tibial epifiz kırığı nedeniyle opere edilen 27 hasta geriye dönük olarak değerlendirildi. Travma mekanizması, fiksasyon tekniği, ameliyat öncesi süre, kırık tipinin klinik sonuçlar ve EBD üzerine etkileri incelendi. Klinik sonuçlar AOFAS (Amerikan Ortopedik Ayak ve Ayak Bileği Skoru) ve MOXFQ (Manchester-Oxford Ayak Anketi) skorları ile değerlendirildi. BULGULAR: Çalışmaya alınan 27 hastanın 17’si erkek, 10’u kadındı. Hastaların yaş ortalaması 11.9 idi (dağılım 5–17 yaş). Epifizyal hasarın en önemli komplikasyonu sekiz hastada büyüme duraklamasıydı. Travma mekanizması, fiksasyon teknikleri ve kırık paternine göre klinik skorlar ve komplikasyonlar açısından istatistiksel olarak anlamlı bir fark gözlenmedi (p>0.05). TARTIŞMA: Travma mekanizması, kırık paterni ve fiksasyon materyali ne olursa olsun, distal tibial epifiz kırıklarında komplikasyonları azaltmak ve EBD’yi önlemek için anatomik bir redüksiyon elde edilmelidir. Anahtar sözcükler: Distal tibial epifiz kırıkları; epifiz büyümesi duraksaması; fiksasyon tekniği; kırık paterni. Ulus Travma Acil Cerrahi Derg 2020;26(3):425-430

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ORIGIN A L A R T IC L E

Computed tomography vs. magnetic resonance imaging in unstable cervical spine injuries Meltem Songür Kodik, M.D.,1 Cenk Eraslan, M.D.,2 Hüseyin Biçeroğlu, M.D.,3 Ali Akay, M.D.4

Ömer Kitiş, M.D.,2

1

Department of Emergency Medicine, Ege University Faculty of Medicine, İzmir-Turkey

2

Department of Radiology, Ege University Faculty of Medicine, İzmir-Turkey

3

Department of Neurosurgery, Ege University Faculty of Medicine, İzmir-Turkey

4

Department of Neurosurgery, Kent Hospital, İzmir-Turkey

Yusuf Ali Altuncı, M.D.,1

ABSTRACT BACKGROUND: This study aimed to investigate the role of computed tomography (CT) in identifying missed unstable blunt cervical injuries. METHODS: Patients admitted to the emergency department between June 2014 and June 2018 with a diagnosis of blunt cervical trauma were included in this study. All participants underwent cervical magnetic resonance imaging (MRI) after an initial cervical CT investigation. All imaging results were reviewed, and decisions were taken by the consensus of a team consisting of an emergency medicine specialist, a neuroradiologist, and a neurosurgeon. Other variables included age, sex, the Glasgow Coma Scale, medical comorbidities, multi-trauma, neurological deficits, accompanying intracranial hemorrhage, extremity fractures, and the mechanism of the injury. RESULTS: Data for 195 patients were analyzed. The mean (±standard deviation) age of the participants was 47.34±21.90 years, and 140 (71.8%) were males. Eighteen patients (9.2%) were below age <18. The most frequent mechanism of injury was fall from height (n=100; 51.3%). Using MRI as the gold standard, the sensitivity of CT in diagnosing unstable cervical injury was 77.7% (95% CI [67.1–86.1]), while its specificity was 100.0% (95% CI [59.0–100.0]). CONCLUSION: Although computed tomography is relatively good in diagnosing unstable cervical injuries, its sensitivity in detecting positive cases is not as successful. Thus, the use of MRI in patients with an unstable injury seems to be warranted. Keywords: Cervical vertebrae; computed tomography; magnetic resonance imaging; neck injuries; sensitivity and specificity.

INTRODUCTION Background/Rationale Cervical spine injuries (CSI) are rare in blunt trauma but may lead to devastating morbidity and mortality. They constitute approximately 1–3% of all blunt trauma cases[1] and 0.2% of all emergency service applications.[2] Spinal cord injuries accompany 0.07–0.26% of this group.[3,4] Early diagnosis is critical because delayed or undiagnosed unstable injuries may have serious consequences.[5]

Studies of both the National Emergency X-Radiography Utilization (NEXUS)[6] and Canadian C-Spine Rule (CCR) [7] are landmarks in the management of suspected cervical trauma. Both tools are decision rules to guide the use of cervical-spine radiography in patients with trauma. Computed tomography (CT)[8] and magnetic resonance imaging (MRI) [9] are longstanding methods as diagnostic screening tools to clear unstable injury in blunt cervical trauma cases. However, there is some disagreement regarding the use of imaging after a negative CT.[10,11]

Cite this article as: Songür Kodik M, Eraslan C, Kitiş Ö, Altuncı YA, Biçeroğlu H, Akay A. Computed tomography vs. magnetic resonance imaging in unstable cervical spine injuries. Ulus Travma Acil Cerrahi Derg 2020;26:431-438. Address for correspondence: Meltem Songür Kodik, M.D. Ege Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, İzmir, Turkey Tel: +90 532 - 384 13 53 E-mail: songurm@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(3):431-438 DOI: 10.14744/tjtes.2019.35813 Submitted: 03.02.2019 Accepted: 21.08.2019 Online: 14.10.2019 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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The majority of cervical spine injuries are fractures; ligamentous and combined injuries are less frequent.[12] However, the MRI is superior to CT for diagnosing soft tissue and spinal cord injuries. Thus, the MRI may target isolated, unstable ligamentous injuries when screening blunt trauma cases for unstable CSI with negative CT.[9] In light of this, we may hypothesize that “edema,” “sprain,” and “contractures” missed following a negative CT can be detected and reported by the MRI.

Patients admitted (2014-2018) n=785 343

ICD Code S12 or S17 n=14 795

Objectives This study aims to assess the utility of MRI after a CT, and examine findings on MRI and assess their effects on the treatment and outcome of stable and unstable injuries.

Excluded (Coding error) n=57

MATERIALS AND METHODS Study Design

Files reviewed

This study was conducted in a cross-sectional plan. Study reporting was prepared following the STROBE guidelines.[13] The study protocol was approved by the Local Ethics Committee at Ege University Medical Faculty (IRB number: 184.1/39; Date: 17 April 2018).

n=14 738

CT+MRI within 48 hours n=198

Setting This study was approved and conducted in the Department of Emergency Medicine at Ege University Faculty of Medicine. This tertiary health care center annually serves around 200 thousand patients in Izmir, Turkey.

Excluded (Missing data) n=3

Participants Data collection was performed using the hospital’s electronic medical records. The registry was searched between 01.06.2014 and 31.06.2018 for the ICD-10 codes S17 (Crushing injury of the neck) and S12 (Fracture of cervical vertebra and other parts of the neck). All files registered with these codes were revised. Of the 14850 cases retrieved, 112 were excluded from this study because of some other diagnoses. From the remaining 14738 patients, 198 who underwent a CT scan followed by MRI within 48 hours of admission were included in this study. Patients with non-diagnostic CT results and/or incomplete medical records were excluded at this stage (Fig. 1, patient flow diagram).

Variables The primary outcome variables of this study were the presence or absence of any pathology in the CT and MRI. Data were collected for other variables, such as age, sex, the mechanism of injury, intensity of trauma (Low energy trauma (LET) vs. High energy trauma (HET), discharge location, and treatments about the CS. HET was defined per the Dutch National Ambulance Protocol, version 7.2, on triage criteria. [14] Clinical data collected consisted of the Glasgow Coma Scale, medical comorbidities, neurological deficits, accompanying intracranial hemorrhage, and extremity fractures. 432

Analyzed n=195

Figure 1. Patient flow diagram.

All CT scans were performed with a GE Discovery HD 750 (GE Healthcare, Milwaukee, WI). The MRI scans were performed with either a 1.5 Tesla Siemens Symphony or 3 Tesla Siemens Avanto CMR scanner (Siemens Medical Solutions, Erlangen, Germany). All CT and MR images were assessed by an emergency medicine specialist, a neuroradiologist, and a neurosurgeon to classify interpretations as ‘negative’ or ‘positive’ for acute traumatic injury patients. Studies interpreted unequivocally as negative for CSI were classified as ‘Negative CT.’ The results were classified as ‘Positive CT’ if impressions included any of the following features: major fractures of vertebrae, disc space widening, vertebral subluxation, epidural hematoma, and prevertebral or paravertebral edema/hematoma. Patients were classified as having a ‘Positive MRI’ if they had any of the following features: ligamentous injury, posttraumatic spinal cord pathological signal changes or hemorrhage, epidural/subdural hematoma, new or acute disc herniation, and Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Songür Kodik et al., Comparison of CT and MRI in cervical spine injuries

prevertebral edema or hematoma. MRI studies interpreted unequivocally as negative for any of the above findings were classified as ‘Negative MRI.’

were male, 55 (28.2%) were female, and 18 (9.2%) were under the age of 18 years. Sixty-one patients (31.3%) had some comorbidities.

As a result of the file investigations, the patients categorized as having “stable” or “unstable” injury. The definitions of unstable injury were based on the neurological status of the patient, the degree of spinal canal stenosis, and the degree of instability. The commonly accepted, Denis’ 1983 delineation was used in the definition of unstable CSI as a single-level ligamentous injury extending to two or three columns.[15]

Descriptive Data

Of the more modern classification systems, the SLIC (Sub axial injury classification system)[16] proposed by the Spinal Trauma Study Group was used. The system is based on the injury morphology, competency of the discoligamentous complex (DLC), and the neurological status of the patient. Conservative treatment is indicated for a score of 3 or less, whereas a score of 5 or higher suggests operative intervention.

Bias All the retrieved files were inspected by two emergency medicine specialists. All imaging results were reviewed and decisions were taken by the consensus of a team consisting of an emergency medicine specialist, a neuroradiologist, and a neurosurgeon. To prevent bias, error checking and debugging were done after the data was entered into the computer.

Study Size

Of the 785 343 patients admitted to the emergency unit, 14738 (1.8%) were due to blunt cervical trauma. Of these cases, on the other hand, 145 (0.9%) was identified as cervical injuries, whereas 88 (0.6%) of them was unstable cervical injuries confirmed by CT and MRI. Fall from high accounted for the most common mechanism of injury (51.3%; n=100). Ninety-nine patients (50.8%) had multiple trauma. One hundred five patients (53.8%) had high energy trauma, while 90 (46.2%) patients had low energy trauma (Table 1). There was no difference between males and females concerning the mechanism of injury or patient outcomes (p>0.05). Most of the patients (97.9%; n=191) had a Glasgow Coma Scale of above 13 and were alert (98.5%; n=192). Surgical intervention was required for 39 patients (20.0%) and one patient (0.5%) died.

Outcome Data Twenty of the 131 cases (15.2%) in the total population and Table 1. Distributions of the trauma mechanisms and patient outcomes

No Yes

The post-hoc sample size was calculated based on a 0.2%[2] expected prevalence of cervical spine injuries among emergency service applications. Given a finite population of 785 343, an expected prevalence of 0.2%, and a margin of error of 3%, a sample size of 146 cases is required to estimate cervical spine injuries in the study population with a confidence interval of 99%.[17]

Pedestrian

Statistical Analysis

Assault

190 97.4

5 2.6

Other mechanisms of injury

186 95.9

8 4.1

Unknown mechanism

192 98.5

3 1.5

The data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 25.0 software (SPSS Inc., Chicago, IL, USA). The results were presented as frequencies, percentages, means, and standard deviations (SD). The Kolmogorov– Smirnov test was performed to test if the numerical variables were normally distributed. The independent samples t-test was used to compare numerical data, and the Chi-square test was used for categorical variables. The sensitivity and specificity of CT were calculated considering MRI as the gold-standard. A p-value of <0.05 was considered statistically significant.

RESULTS Participants Results for 195 blunt cervical trauma patients were analyzed in this study. The patients had a mean age of 47.34±21.90 years (min 1, max 90). Of the patients, 140 patients (71.8%) Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

n %

n %

Mechanism of injury

Fall from height

Motor vehicle accident

95 48.7

100 51.3

130 66.7

65 33.3

178 91.3

17 8.7

Patient outcome Neurologic deficit Conscious

Intracranial hemorrhage

Extremity fracture

171 87.7

24 12.3

3 1.5

192 98.5

181 92.8

14 7.2

163 83.6

32 16.4

Any bony fracture

117 60.0

78 40.0

Spinal cord injury

175 89.7

20 10.3

ALL injury

165 84.6

30 14.4

185 94.9

10 5.1

Suboccipital ligament injury

Unstable injury

107 54.9

88 45.1

Operation

156 80.0

39 20.0

Exitus

194 99.5

1 0.5

ALL: Anterior longitudinal ligament.

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18 of the 25 cases (72%) among the unstable CSI cases with a negative CT had positive findings in the MRI. Besides, the mean ages of the CT-positive (54.55±21.77), as well as MRIpositive (54.29±22.28) cases, were significantly higher (t and

p, -3.292; 0.001 and -3.955; <0.001, respectively) compared to the negative cases (43.82±21.17 vs. 42.19±20.22, respectively). When CT and MRI were compared for positive results in different conditions, it was observed that they had similar

Table 2. Comparison of the CT and MRI results concerning different mechanisms of injury and patient outcomes CT MRI Negative Positive Negative Positive Fall from height No Yes Motor vehicle accident No Yes Pedestrian No Yes Assault No Yes High energy trauma No Yes Neurologic deficit No Yes Extremity fracture No Yes Any bony fracture No Yes Spinal cord injury No Yes ALL injury No Yes Suboccipital ligament injury No Yes Operation No Yes Unstable No Yes SLIC score 0 1 2 GCS score ≤13 >13

n % n %

χ2, p

n

%

n

%

χ2, p

71 54.2 24 37.5 4.799, 0.028 60 45.8 40 62.5

66 58.9 29 34.9 46 41.1 54 65.1

10.981, 0.001

85 64.9 45 70.3 0.570, 0.450 46 35.1 19 29.7

69 61.6 61 73.5 43 38.4 22 26.5

3.031, 0.082

117 89.3 61 95.3 1.945, 0.163 14 10.7 3 4.7

100 89.3 78 94.0 12 10.7 5 6.0

1.318, 0.251

126 96.2 64 100.0 2.507, 0.113 5 3.8 0 0.0

107 95.5 83 100.0 5 4.5 0 0.0

3.803, 0.051

86 95.5 4 4.4 61.039, <0.001 45 42.9 60 57.1

84 93.3 6 6.7 28 26.7 77 73.3

88.102, <0.001

116 88.5 55 85.9 0.272, 0.602 15 11.5 9 14.1

99 88.4 72 86.7 13 11.6 11 13.3

0.120, 0.729

112 85.5 51 79.7 1.058, 0.304 19 14.5 13 20.3

95 84.8 68 81.9 17 15.2 15 18.1

0.291, 0.590

96 82.1 21 17.9 29.341, <0.001 35 44.9 43 55.1

88 75.2 29 24.8 24 30.8 54 69.2

37.814, <0.001

127 72.6 48 27.4 22.498, <0.001 4 20.0 16 80.0

110 62.9 65 37.1 2 10.0 18 90.0

20.512, <0.001

119 72.1 46 27.9 11.879, 0.001 12 40.0 18 60.0

106 62.4 59 35.8 6 20.0 24 80.0

20.325, <0.001

131 70.8 54 29.2 21.575, <0.001 0 0.0 10 100.0

112 60.5 73 39.5 14.223, <0.001 0 0.0 10 100.0

119 90.8 37 57.8 29.312, <0.001 12 9.2 27 42.2

104 92.9 52 62.7 8 7.1 31 37.3

27.186, <0.001

106 80.9 1 1.6 109.333, <0.001 25 19.1 63 98.4

105 93.8 2 2.4 7 6.3 81 97.6

160.616, <0.001

17 36.2 30 63.8 4.765, 0.092 5 31.3 11 68.8 3 12.0 22 88.0 3 75.0 1 25.0 0.113, 0.736 128 67.0 63 33.0

6 12.8 41 87.2 0 0.0 16 100.0 7 8.0 81 92.0 3 75.0 1 25.0 109 57.1 82 42.9

3.403, 0.182

0.515, 0.473

CT: Computed tomography; MRI: Magnetic resonance imaging; SLIC: Subaxial Cervical Spine Injury Classification; GCS: Glasgow Coma Scale; ALL: Anterior longitudinal ligament.

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Table 3. Performance of computed tomography compared to MRI in the detection of all cervical injuries and unstable cervical injuries All cases

MRI

Negative Positive

Total

Computed tomography Negative Positive Total

111

20

131

1

63

64

112

83

195

Unstable cervical injuries MRI

Negative Positive

Total

Computed tomography Negative

7

18

25

Positive

0

63

63

Total

7

81

88

MRI: Magnetic resonance imaging.

significances (Table 2). However, the MRI yielded somewhat more positive results compared to CT. Neither CT nor MRI showed the importance in differentiating between different SLIC score categories.

(a)

(d)

The sensitivity and specificity of CT in detecting any cervical injury was calculated as 75.9% (95% CI [65.2–84.6]) and 99.1% (95% CI [95.1–99.9]), respectively (Table 3), whereas the sensitivity and specificity of CT in detecting unstable cervical injuries were calculated as 77.7% (95% CI [67.1–86.1]) and 100.0% (95% CI [59.0≠100.0]), respectively. While 6.5% (n=7) of the stable injuries were operated, 36.4% (n=39) of the unstable patients got operated (ChiSquare=26.839; p<0.001). The CT and MR images of one representative case are presented in Figure 2. As seen in the images, vertebral dislocation and narrowing of the spinal canal can be identified in both the CT and MRI. However, myelopathic signal changes at the spinal cord can only be detected on the MR images.

DISCUSSION Key Results The prevalence of blunt cervical trauma among patients admitted to the emergency department was found at 1.8%. On the other hand, the frequency of unstable cervical injuries confirmed by CT and MRI was calculated as 0.6%. Besides, this study confirms that CT alone is not sufficient in eliminating cervical spinal injuries in patients with blunt trauma. A

(b)

(e)

(c)

(f)

Figure 1. Patient flow diagram.

Figure 2. Axial (a) and reformatted sagittal (b) and coronal (c) CT images of the cervical spine. Multiple fractures and dislocation are seen at the level of C5 and C6 vertebrae. Sagittal T2 (d), sagittal TIRM (e), and axial T2 (f) MR images of the cervical spine and spinal cord show myelopathic signal changes at the level of C5 vertebrae in the spinal cord

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significant proportion of unstable CSI cases missed by the CT could be identified using MRI.

Limitations This is a retrospective study carrying the general limitations of file studies. Beyond the issues related to the robustness of the recorded data, the study population has a wide age range, with demonstrated diversities between children and adults.[18] Additionally, it would be valuable to receive the interpretations of the treating surgeons on the radiological images as well. Furthermore, the study lacks information about long-term follow-up and complication rates. It is possible that there are missed cases in the emergency ward, who experienced some complications. On the other hand, the study hospital receives a significant number of referrals from other institutions. Thus, the high number of the patient influx in the study center can be regarded as an advantage of this study.

Interpretation Demographic differences are observed in many disease entities, including cervical spine injuries. Among patients undergoing cervical spine radiography in the emergency department, cervical spine injury was more common among the elderly, male subjects.[18] However, we did not observe any difference concerning sex. Obtunded patients need special attention due to their difficulty in obtaining a reliable physical examination. Although different GCS cut-off levels were proposed to describe obtunded, per the suggestion of Tomycz et al.,[19] we have chosen the threshold as less than 13 and 13 and above. In our sample, only four patients had a GCS score of 13 or less.

NEXUS led to the diagnosis of significant injuries in two patients, which would otherwise have been missed.[24] Malhotra et al.[9] reported 15% of the MRI abnormalities consequent a negative CT. Menaker et al.[25] found 9% abnormal MRI results after an initial CT scan and, thus, advocated the continued use of MRI. The MRI has been preferred for further imaging in unconscious or clinically unevaluable patients.[26] However, the MRI is used frequently, even in alert and awake patients. As to the study of Inaba et al.,[27] 19% of alert and awake patients with a Glasgow Coma Scale Score of 14 to 15 failed the NEXUS low-risk criteria and necessitated CT authorization. Besides, the definition and clinical significance of unstable injury vary between studies and individual doctors. The most commonly used definition of “significant injury” is the three-column model based on NEXUS,[28] which were also utilized in our study. On the other hand, some studies have stressed that MRI is unnecessary. Hogan et al.[29] diagnosed 3.3% injuries by MRI that were not evident on CT; however, none of those injuries were radiographically unstable. Como et al.[30] reported that they removed MRI from their treatment algorithm and did not observe any cases of new neurologic deficits on a 2-year follow-up. Also, Tomycz et al.[19] defended that MRI was not necessary to clear the cervical spine. As reported by Khanna et al.,[31] 49% of the patients without diagnostic clues in the CT scans had injuries identified on MRI, but they all were deemed insignificant. Despite the agreement that the MRI is superior in identifying ligamentous and soft-tissue injuries, the objections for its routine use rely on the relatively low clinical importance of these soft tissue injuries that may not necessitate treatment.

Algorithms, such as the Canadian C-spine Rule (CCR) and the NEXUS criteria, have been developed to reduce the rates of unnecessary radiography.[20] However, given the significant morbidities and mortalities associated with cervical trauma, it is understandable that clinicians are cautious in overlooking injuries. In blunt injury patients, assessment of possible instability and avoidance of secondary injury is the primary goals of cervical spine clearance protocols. After a missed spinal injury, the incidence of avoidable neurological deterioration has been reported as high as 60%.[21] Thus, it is usual to observe high tech laboratory investigations in the context of emergency services.

Factors affecting the diagnostic capability of MRI should be considered as well. MRI is sensitive in demonstrating acute edema of the soft tissues within the first 72 hours of the event.[6] Short after this period, soft tissue edema decreases and injury may no longer be visualized by the MRI. In this study, we included only imaging results within the first 48 hours. On the other hand, MRI may be risky, particularly in severely injured unstable patients, because the patient has to be transported from the intensive care unit to a less safe site. Also, the supine position of patients in the gantry of the MRI may lead to increased intracranial pressure, aspiration, and hypoxia. Additionally, the MRI cannot be performed for patients with ferric implants.[32]

In awake and alert patients who are neurologically intact and without distracting injury, the NEXUS low-risk criteria and the CCR study have proposed that imaging is not necessary. [22,23] However, especially in patients with continuous and persistent cervical tenderness, the use of such criteria is inconsistent.[24] Although for the patients with blunt trauma, where CT has been approved as the standard first step diagnostic tool, the sufficiency of a normal CT result alone, has been observed with doubt. As to one report, the deviation from

On their arrival, many of the trauma patients have a cervical collar. The routine practice in the study institution in such cases is combined ordering of MRI and CT. The MRI is expensive compared to CT. However, this difference is negligible for Turkey. As to the current official communiqué of the Turkish Social Security Institution, a cervical CT costs 63.23 TL (12.14 USD), while an MRI costs 74.72 TL (14.35 USD). [33] Although there are discussions on the cost-effectiveness of MRI, its utility in diagnosing CSI is well-established.[9,11] We

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consider that from the standpoint of the devastating and irreversible nature of missed CSI, the expenses of MRI obviously counterbalance the upkeep of a quadriplegic in our context.

Conclusion Interpreted in the light of the heterogeneous literature, our results suggest that the use of MRI to diagnose unstable CSI injury in patients with negative CT findings depends on the decision of emergency physicians, consultant neurosurgeons and neuroradiologists in charge. Even after neurological evaluation and a well-performed negative CT in unstable injuries, obtaining an MRI seems to be justified. Given the serious consequences, all efforts should be made to reach 100% sensitivity in detecting CSI and strive to avoid neurological complications. The authors advocate the continued use of MRI in the detection of unstable CSI. Ethics Committee Approval: The study protocol was approved by the Local Ethics Committee at Ege University Medical Faculty (IRB number: 18-4.1/39; Date: 17 April 2018). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: M.S.K., C.E., Ö.K.; Design: M.S.K., C.E.; Supervision: H.B., A.A.; Materials: M.S.K., C.E.; Data: M.S.K., C.E.; Analysis: M.N.O.; Literature search: M.S.K.; Writing: M.S.K.; Critical revision: Y.A.A. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Martin MJ, Bush LD, Inaba K, Byerly S, Schreiber M, Peck KA, et al; WTA C-Spine Study Group. Cervical spine evaluation and clearance in the intoxicated patient: A prospective Western Trauma Association Multi-Institutional Trial and Survey. J Trauma Acute Care Surg 2017;83:1032−40. 2. Zakrison TL, Williams BH. Cervical spine evaluation in the bluntly injured patient. Int J Surg 2016;33:246–50. 3. Reid DC, Henderson R, Saboe L, Miller JD. Etiology and clinical course of missed spine fractures. J Trauma 1987;27:980–6. 4. Plackett TP, Wright F, Baldea AJ, Mosier MJ, Thomas C, Luchette FA, et al. Cervical spine clearance when unable to be cleared clinically: a pooled analysis of combined computed tomography and magnetic resonance imaging. Am J Surg 2016;211:115−21. 5. Harris MB, Kronlage SC, Carboni PA, Robert KQ, Menmuir B, Ricciardi JE, et al. Evaluation of the cervical spine in the polytrauma patient. Spine (Phila Pa 1976) 2000;25:2884−91; discussion 2892. 6. Hoffman JR, Wolfson AB, Todd K, Mower WR. Selective cervical spine radiography in blunt trauma: methodology of the National Emergency X-Radiography Utilization Study (NEXUS). Ann Emerg Med 1998;32:461–9. 7. Stiell IG, Wells GA, Vandemheen KL, Clement CM, Lesiuk H, De Maio VJ, et al. The Canadian C-spine rule for radiography in alert and stable trauma patients. JAMA 2001;286:1841−8. 8. Holmes JF, Akkinepalli R. Computed tomography versus plain radiography to screen for cervical spine injury: a meta-analysis. J Trauma

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2005;58:902–5. 9. Malhotra A, Wu X, Kalra VB, Nardini HK, Liu R, Abbed KM, et al. Utility of MRI for cervical spine clearance after blunt traumatic injury: a meta-analysis. Eur Radiol 2017;27:1148−60. 10. Malhotra A, Wu X, Mahalingam S. Cervical spine magnetic resonance imaging in blunt cervical trauma patients. J Trauma Acute Care Surg 2017;83:748–9. 11. Maung AA, Johnson DC, Barre K, Peponis T, Mesar T, Velmahos GC, et al; ReCONECT MRI C-SPINE Study Group. Cervical spine MRI in patients with negative CT: A prospective, multicenter study of the Research Consortium of New England Centers for Trauma (ReCONECT). J Trauma Acute Care Surg 2017;82:263−9. 12. Young AJ, Wolfe L, Tinkoff G, Duane TM. Assessing Incidence and Risk Factors of Cervical Spine Injury in Blunt Trauma Patients Using the National Trauma Data Bank. Am Surg 2015;81:879–83. 13. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Version 2. PLoS Med 2007;4:e296. 14. van Laarhoven JJ, Lansink KW, van Heijl M, Lichtveld RA, Leenen LP. Accuracy of the field triage protocol in selecting severely injured patients after high energy trauma. Injury 2014;45:869–73. 15. Denis F. The three column spine and its significance in the classification of acute thoracolumbar spinal injuries. Spine (Phila Pa 1976) 1983;8:817– 31. 16. Vaccaro AR, Hulbert RJ, Patel AA, Fisher C, Dvorak M, Lehman RA Jr, et al; Spine Trauma Study Group. The subaxial cervical spine injury classification system: a novel approach to recognize the importance of morphology, neurology, and integrity of the disco-ligamentous complex. Spine (Phila Pa 1976) 2007;32:2365−74. 17. Lenth R. Java Applets for Power and Sample Size [Computer software] 2009. Available from: https://homepage.divms.uiowa.edu/~rlenth/ Power/. Accessed May 24, 2018. 18. Lowery DW, Wald MM, Browne BJ, Tigges S, Hoffman JR, Mower WR; NEXUS Group. Epidemiology of cervical spine injury victims. Ann Emerg Med 2001;38:12−6. 19. Tomycz ND, Chew BG, Chang YF, Darby JM, Gunn SR, Nicholas DH, et al. MRI is unnecessary to clear the cervical spine in obtunded/ comatose trauma patients: the four-year experience of a level I trauma center. J Trauma 2008;64:1258–63. 20. Stiell IG, Clement CM, McKnight RD, Brison R, Schull MJ, Rowe BH, et al. The Canadian C-spine rule versus the NEXUS low-risk criteria in patients with trauma. N Engl J Med 2003;349:2510–8. 21. Todd NV, Skinner D, Wilson-MacDonald J. Secondary neurological deterioration in traumatic spinal injury: data from medicolegal cases. Bone Joint J 2015;97-B:527–31. 22. Griffith B, Bolton C, Goyal N, Brown ML, Jain R. Screening cervical spine CT in a level I trauma center: overutilization?. AJR Am J Roentgenol 2011;197:463–7. 23. Duane TM, Wilson SP, Mayglothling J, Wolfe LG, Aboutanos MB, Whelan JF, et al. Canadian Cervical Spine rule compared with computed tomography: a prospective analysis. J Trauma 2011;71:352−5; discussion 355−7. 24. Morrison J, Jeanmonod R. Imaging in the NEXUS-negative patient: when we break the rule. Am J Emerg Med 2014;32:67–70. 25. Menaker J, Philp A, Boswell S, Scalea TM. Computed tomography alone for cervical spine clearance in the unreliable patient--are we there yet?. J Trauma 2008;64:898–904.

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Claridge JA. Computed tomography alone may clear the cervical spine in obtunded blunt trauma patients: a prospective evaluation of a revised protocol. J Trauma 2011;70:345–51. 31. Khanna P, Chau C, Dublin A, Kim K, Wisner D. The value of cervical magnetic resonance imaging in the evaluation of the obtunded or comatose patient with cervical trauma, no other abnormal neurological findings, and a normal cervical computed tomography. J Trauma Acute Care Surg 2012;72:699–702. 32. Dunham CM, Brocker BP, Collier BD, Gemmel DJ. Risks associated with magnetic resonance imaging and cervical collar in comatose, blunt trauma patients with negative comprehensive cervical spine computed tomography and no apparent spinal deficit. Crit Care 2008;12:R89. 33. Communique on the changes in the Social Security Institution [Sosyal Güvenlik Kurumu sağlık uygulama tebliğinde değişiklik yapılmasına dair tebliğ]. Off Gaz Repub Turkey 2018;July 5. Available from: https://www. resmigazete.gov.tr/eskiler/2018/07/20180705M1-1.htm.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Anstabil servikal yaralanmalarda bilgisayarlı tomografi ve manyetik rezonans görüntüleme bulgularının karşılaştırılması Dr. Meltem Songür Kodik,1 Dr. Cenk Eraslan,2 Dr. Ömer Kitiş,2 Dr. Yusuf Ali Altuncı,1 Dr. Hüseyin Biçeroğlu,3 Dr. Ali Akay4 Ege Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, İzmir Ege Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, İzmir 3 Ege Üniversitesi Tıp Fakültesi, Beyin Cerrahisi Anabilim Dalı, İzmir 4 Kent Hastanesi, Beyin Cerrahisi Bölümü, İzmir 1 2

AMAÇ: Bu çalışmanın amacı atlanabilen anstabil servikal yaralanmaların belirlenmesinde bilgisayarlı tomografinin (BT) rolünü araştırmaktır. GEREÇ VE YÖNTEM: Bu çalışmada acil servise Haziran 2014 ile Haziran 2018 arasında künt servikal travma tanısı ile başvuran olgular yer almaktadır. Tüm olgular ilk önce yapılan bir BT incelemesini takiben servikal manyetik rezonans görüntülemesine (MRG) tabi tutulmuşlardır. Tüm görüntüleme sonuçları gözden geçirilmiş ve kararlar acil tıp uzmanı, nöroradyolojist ve beyin cerrahından oluşan bir ekip tarafından fikir birliği ile alınmıştır. Diğer değişkenler arasında yaş, cinsiyet, Glasgow koma skalası, ek morbidite, çoklu travma, nörolojik defisitler, intrakraniyal hemoraji, ekstremite kırıkları ve yaralanmanın mekanizması yer almaktadır. BULGULAR: Çalışmaya alınan 195 hastanın bilgileri analiz edildiğinde; hastaların ortalama yaşı (±standart sapma) 47.34±21.90 yıl olup 140’ı erkek (%71.8) 18’i (%9.2) 18 yaşın altında idi. En sık görülen yaralanma mekanizması yüksekten düşme idi (n=100; %51.3). Altın standart olarak MRG kullanılmış olup, anstabil servikal travma tanısında BT’nin duyarlılığı %77.7 (%95 GA [67.1–86.1]) iken, özgüllüğü %100.0 (%95 GA [59.0–100.0]) saptanmıştır. TARTIŞMA: Her ne kadar BT anstabil servikal yaralanmaların tanısında rölatif olarak iyi olsa da duyarlılığı yeterli değildir. Bundan dolayı anstabil yaralanması olan olgularda MRG çekilmesi daha uygundur. Anahtar sözcükler: Bilgisayarlı tomografi; boyun yaralanmaları; manyetik rezonans görüntüleme; sensivite ve spesifite; servikal vertebra. Ulus Travma Acil Cerrahi Derg 2020;26(3):431-438

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doi: 10.14744/tjtes.2019.35813

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ORIGIN A L A R T IC L E

Effect on mortality of treatment method and surgery time for hip fracture patients aged over 65 years Cihat Ekici, M.D., Özhan Pazarcı, M.D., Seyran Kılınç, M.D., Zekeriya Öztemür, M.D., Hayati Öztürk, M.D., Gündüz Tezeren, M.D., Okay Bulut, M.D. Department of Orthopaedics and Traumatology, Cumhuriyet University Faculty of Medicine, Sivas-Turkey

ABSTRACT BACKGROUND: This study aimed to evaluate the effects on mortality of implant selection used and time to surgery in patients aged over 65 years operated for hip fractures. METHODS: A total of 301 patients aged over 65 years were investigated in this study. Patients were divided into three groups as follows: Group 1 cemented hemiarthroplasty (CH), Group 2 cementless hemiarthroplasty (CLH), and Group 3 proximal femoral nail (PFN). Time of surgery, fracture and demographic information were retrospectively recorded. RESULTS: After removing 59 patients with missing information, this study included 242 patients. Mean age of patients was 80.5 years. When patient groups were examined according to treatment method, Group 1 (n=146) comprised 60.3%, Group 2 (n=54) comprised 22.3% and Group 3 (n=42) comprised 17.4% of the study group. There was no significant difference in survival between the patients operated in the first 48 hours and the patients operated later (p=0.834). There was an effect on the survival of treatment implant selection (p=0.016). Patients with CH were observed to survive longer than patients with CLH and PFN. CONCLUSION: Operation in the first 48 hours was not observed to affect mortality. Additionally, while sex and age were found to be effective on mortality, implant selection was also concluded to affect mortality. Keywords: Hemiarthroplasty; hip fracture; mortality; proximal femoral nail; surgery time.

INTRODUCTION All future population projections predict increasing elderly populations,[1] which shows that there will be an increase in the frequency of elderly patients with osteoporotic hip fractures.[2] The main principles of treatment in osteoporotic hip fracture patients are to provide appropriate treatment to prevent mortality and morbidity and to rapidly make the patient mobile.[3] Treatment for hip fractures over 65 years is determined considering the physiologic age of the patient, activity, presence of systemic diseases, bone quality and fracture displacement degree. Among treatment selections for osteoporotic hip fracture patients, proximal femoral nail (PFN) and cemented

hemiarthroplasty (CH) or cementless hemiarthroplasty (CLH) are commonly chosen. These treatment methods involve advantages and disadvantages. In the literature, there are studies investigating the correlation between the implant used for hip fracture treatment and mortality.[4–6] However, to date, to our knowledge, there is no gold standard treatment defined for elderly hip fracture patients. There are many studies investigating the effects of time of surgery on mortality in hip fractures.[5,7] A significant degree of reduction for mortality was reported for hip fractures operated within the first 48 hours.[8] Additionally, there are studies reporting the opinion that elderly patients should be operated at the earliest possible time allowed by their medical status.[9,10] In this context, the hypothesis we tested in this

Cite this article as: Ekici C, Pazarcı Ö, Kılınç S, Öztemür Z, Öztürk H, Tezeren G, et al. Effect on mortality of treatment method and surgery time for hip fracture patients aged over 65 years. Ulus Travma Acil Cerrahi Derg 2020;26:439-444. Address for correspondence: Özhan Pazarcı, M.D. Cumhuriyet Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Sivas, Turkey Tel: +90 346 - 219 11 56 E-mail: dr.pazarci@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):439-444 DOI: 10.14744/tjtes.2020.81780 Submitted: 26.06.2019 Accepted: 11.02.2020 Online: 13.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Ekici et al. Effect on mortality of treatment method and surgery time for hip fracture patients aged over 65 years

study is the question of whether implant selection or time of surgery is effective on mortality. Thus, this study aims to evaluate the effects on mortality of the implant type used and the time of surgery in patients aged over 65 years operated for hip fracture.

(a)

(b)

MATERIALS AND METHODS Local ethics committee permission was received on 26.03.2019 numbered 2018-03/27. This study included patients attending our clinic for hip fracture from January 2012 to January 2016. Of these, patients with less than two years follow-up and under the age of 65 were excluded from this study. A patient pool of 301 patients older than 65 years was formed. Fifty-nine patients without patient follow-up information or who left clinical follow-up were excluded. Thus, 242 patients were investigated (Table 1). Patients were divided into three groups according to implant selected for treatment as CH, CHL and PFN (Figs. 1–3). The demographic information, comorbid diseases, American Society of Anesthesiologists (ASA) score, time of surgery, type of anesthesia, type of treatment, duration of hospital stay, duration of fol-

Figure 1. 82-year-old patient with cemented hemiarthroplasty (CH) radiographs (a) preop, (b) postop.

(a)

(b)

Table 1. Methodology flow chart 1. This study included 301 patients aged over 65 years with hip

fracture from January 2012 to 2016.

2. Preop and postop follow-up radiographs examined in the

PACS system and 59 patients without follow-up radiographs

were excluded from this study.

3. Fractures classified according to AO. 4. Patient information collected from files retrospectively.

• Demographic data

• Comorbid diseases

• ASA score

• Time of surgery

• Type of anesthesia

• Form of treatment

• Hospital stay

• Complications

Figure 2. Radiographs of a 70-year-old patient with cementless hemiarthroplasty (CLH) (a) preop, (b) postop.

(a)

(b)

5. Time of death recorded for patients from the national

mortality records.

6. Data from 242 patients were investigated in three groups

according to the treatment method.

Group 1

146 patients with CH

Group 2

Group 3

54 patients with

42 patients with

CLH

PFN

PACS: Picture Archiving & Communication Systems; AO: Arbeitsgemeinschaft für Osteosynthesefragen; ASA: American Society of Anesthesiologists; CH: Cemented hemiarthroplasty; CLH: Cementless hemiarthroplasty; PFN: Proximal femoral nail.

440

Figure 3. Radiographs of a 75-year-old female patient who underwent proximal femoral nail (PFN) (a) preop, (b) postop.

low-up and presence of complications were recorded from patient files. Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Ekici et al. Effect on mortality of treatment method and surgery time for hip fracture patients aged over 65 years

Preop and postop radiography of patients was investigated using our hospital’s Picture Archiving & Communication Systems (PACS) system. The time of death of patients was noted by searching the National Mortality Report System (MRS) on 15 May 2018, with survival noted. Fractures were classified according to the Arbeitsgemeinschaft für Osteosynthesefragen (AO) classification. The SPSS (v. 22.0) statistical program was used to analyse the data in this study. Numerical data were given as mean and standard deviation, while categorical data were given as frequency and percentage. Statistical comparison of means used the t-test, with the chi-square test or Fisher’s exact test used for comparison of frequencies. Additionally, patient survival was evaluated using Kaplan-Meier survival analysis. Statistical analysis of differences between group survival used the log-rank test. P-values smaller than 0.05 were accepted as statistically significant.

RESULTS This study included 242 patients, with 136 females and 106 males. Mean age of patients was 80.5 years (65–100). Mean follow-up duration was 30.9 months (0–76). There were 69 cases (28.5%) with at least one comorbid disease, 67 cases (27.6%) with at least two comorbid diseases and 79 cases (32.6%) with three or more comorbid diseases. ASA scoring distribution was six patients (2.5%) with ASA I, 106 patients (43.8%) with ASA II, 118 patients (48.8%) with ASA III and 12 patients (4.9%) with ASA IV. There was no ASA V case. Of patients, 68.1% (n=165) had femoral intertrochanteric fracture and 31.9% (n=77) had femoral neck fracture. The mean duration of hospital stay was 12.3 days (3–66). Of patients, 59 (24.4%) were operated in the first 48 hours. For anesthesia, 175 patients (72.3%) had general

anesthesia and 67 patients (27.7%) had spinal anesthesia administered. When patient groups are examined according to treatment method, Group 1 (CH, n=146) comprised 60.3%, Group 2 (CLH, n=54) comprised 22.3% and Group 3 (PFN, n=42) comprised 17.4% of the study group. Three patients had postop prosthesis infection, and 2 had revision due to implant failure. At the time of the study, 98 patients (40.4%) were surviving, while 144 patients (59.6%) were exitus. The general mortality rate mean was 19 months (0 days-69 months). In the three groups, it was observed that operation in the first 48 hours did not affect mortality (p=0.649). A significant difference was identified in first-year mortality rates according to sex, and these rates were 13% females and 29% males (p<0.05). The mean hospital stay for patients who died within the first year was 14 days (SD: 10.57), while this value was 11.9 days for surviving patients (SD: 6.02) (p<0.05). Also, the type of treatment was found to be statistically significant in this period (p<0.05). Of all patients with the cemented hip prosthesis, 22 (15%) died within 36 months or later, while five patients (11%) in the PFN group and only one patient (1.8%) in the cementless hip prosthesis-patient died in this period (Table 2). Of the surviving 98 patients, the mean age was 78.3 years, while the mean age of the 144 exitus patients was 81.9 years (p<0.05). The firstyear mortality rate was 29%, with general survival of our patients was 19% (Fig. 4). When parameters affecting general survival are investigated, ASA score, presence and number of comorbid diseases, fracture type, and sex differences were not observed to have statistically significant effects on survival. The patients operated in the first 48 hours had no statistically significant difference in survival compared to those operated later (p=0.834). There was a statistically significant effect on the survival of

Table 2. Comparison of the factors affecting mortality Parameters P-values*

Month

1. Time of the surgery

0–1 0.576

1–12

12–24

24–36

>36

Total

0.924

0.301

0.910

0.345

0.649

2. Treatment method

0.158 0.253 0.814 0.584 0.034 0.145

3. ASA score

0.424 0.598 0.936 0.085 0.919 0.178

4. Presence of the comorbid diseases

0.229

0.488

0.172

0.397

0.613

0.339

5. Type of the anesthesia

0.110

0.922

0.607

0.645

0.824

0.883

6. Fracture type

0.310 0.894 0.811 0.823 0.520 0.950

7. Complications

0.007 0.782 0.893 0.864 0.628 0.297

8. Mean age

0.609 0.071 0.133 0.058 0.771 0.001

9. Sex

0.149 0.003 0.825 0.871 0.546 0.086

10. Duration of the hospital stay

0.526

0.049

0.774

0.408

0.337

0.448

P-values smaller than 0.05 were accepted as statistically significant. ASA: American Society of Anesthesiologists.

*

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mortality and morbidity rates observed in elderly patients and increased treatment costs illustrate the importance of this problem.[13] In the literature, there are still debates about the gold standard treatment and ideal surgery time for hip fracture cases.[8–10] Our study shows that implant selection has a statistically significant effect on survival.

1.0

0.8

Patients in our study series were 56% female and 44% male. Males were observed to have fewer hip fractures compared to females; however, mortality rates were observed to be higher. Investigation of survival, according to sex in hip fracture patients, found shorter survival in males compared to the female sex.[14] Similar to our study, Schnell et al.[15] found higher two-year mortality in the male sex. Additionally, our study showed that long hospital stays affected mortality, especially in the period from 1–12 months. Long hospital stays were shown to have negative effects on mortality in the literature.[16] Our view is that the patient should be rehabilitated and discharged in a short period postoperatively.

0.6

0.4

0.2

0.0 .00

20.00 40.00 Time of death (month)

60.00

Figure 4. Graph of the general survival.

PFN CH CHL

1.0

0.8

0.6

0.4

0.2

0.0 .00

20.00 40.00 Time of death (month)

60.00

Figure 5. Graph of survival according to treatment method. PFN: Proximal femoral nail; CH: Cemented hemiarthroplasty; CLH: Cementless hemiarthroplasty.

implant choice for treatment (p=0.016). Patients with CH were observed to have longer survival compared to those with CHL and PFN (Fig. 5).

DISCUSSION The strongest aspect of our study is the assessment of the effects on mortality of the use of different implants and the time of surgery together for the treatment of elderly hip fracture patients. With the increase in the elderly population, hip fracture cases have become a public health problem.[11,12] High 442

Our study found that age was a significant factor affecting general mortality. A study conducted by Forni et al.[17] found that age was the most important factor for mortality in the first month and reported an 8.4% increase in mortality with each year of age increase for patients over 65 years. A study carried out by Paksima et al.[18] showed that age was the most important factor for mortality, consistent with the results of our study. Our opinion is that all mortality factors should be considered, especially in patients with advanced age. All mortality risks should be minimized as much as possible. Of our patients, 24.4% were operated within the first 48 hours. Contrary to the literature, no significant correlation was observed between mortality and time. However, there are studies supporting our research data in the literature. This rate is similar to the large series by Kenzora et al.[19] Our clinic generally operates on patients in the earliest period allowed by their medical status, through operation in the first 48 hours was not shown to have a significant effect on mortality. A study conducted by Sasabuchi et al.[20] found an effect on mortality for 5-day delays in surgery when they controlled for additional variables, including age, chronic diseases and dementia. Al-Ani et al.,[21] in a study with 850 patients, found no difference in mortality for patients operated in 24, 36 and 48 hours. In our study, mortality in the first 30 days was 7.8%, with first-year mortality of 19%. These rates are similar to the literature. A study carried out by Forni et al.[17] about mortality in the first month after hip fracture in the geriatric patient group found this rate was 4.9%. Schnell et al.[15] found a 21.2% 1-year mortality rate in a study of hip fracture patients over 60 years of age. The authors were of the opinion that elderly hip fracture patients and their relatives should be wellinformed about mortality preoperatively. Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Ekici et al. Effect on mortality of treatment method and surgery time for hip fracture patients aged over 65 years

The effects of implant selection used for treatment on mortality are known. Ravikumar et al.[22] investigated the longterm outcomes of internal fixation, hemiarthroplasty and total hip prosthesis for hip fractures and showed the first 2-month mortality was 12% for internal fixation and 15% for hemiarthroplasty. Mortality in the 12 months was 25% for internal fixation and 27% for hemiarthroplasty. However, though internal fixation was superior for first-year survival, internal fixation was not shown to be superior concerning mortality in the long term. Different studies have shown that 5-week mortality for cemented hip prosthesis was higher; however, the difference in mortalities balanced after the 3rd month.[23] As seen in the literature, there is no gold standard treatment recommended for hip fractures. Our study shows that for long-term survival, CH is superior. There is a need for randomized controlled clinical studies to suuport the data from our study. Commonly in the literature, there are studies that have investigated the effects of implant selection on mortality generally retrospectively. In our series, the deep infection rate was 1.2%. A study by Partanen et al.[24] of patients operated for a hip fracture found that deep infection rates were 1.3%, similar to our study. The implant failure was 4.7% in Group 3. Görmeli et al.[5] found that the revision rates due to various reasons, such as implant failure or dislocation, was 11.7% for PFN, while this rate was 2.6% for hemiarthroplasty. Our conclusion is that more complications were identified for patients undergoing hemiarthroplasty due to longer surgery duration and larger surgical incision. Many implant comparison studies have emphasized that complications are observed less in patients with PFN.[25] Many methods are recommended in the literature to avoid these complications. For example, the use of double scopy during PFN surgery is reported to reduce the surgical duration and complication risks.[26] If the surgeon chooses to use PFN, they should choose one of these different designs. [27–29] Another important situation is the anesthesia type and pain management administered to the patient.[30] Different from the literature, in our study, there was no significant correlation found between the form of anesthesia and mortality. There are publications stating that general anesthesia is linked to more mortality in this patient group; however, it can be said that this was observed more in patients with high risk related to cardiac causes.[31] The authors are aware of the limitations of this study. The first limitation is that this study is retrospective. Additionally, the decisions about implant selection for patients were made according to surgeon choice and experience. There is a need for randomized prospective studies in this area. The evaluation of mortality in patients with different ASA scores may be seen as a limitation. However, the difficulty in creating homogeneous groups concerning the ASA score cannot be ignored. Additionally, the distribution of ASA scores among patients in our study group is similar to other studies in the literature.[32] Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

Conclusion Operation in the first 48 hours was not observed to affect mortality. Additionally, while sex and age affected mortality, it was concluded that implant selection also affected mortality. There is a need for prospective controlled studies in this field. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: C.E., Ö.P.; Design: Ö.P., S.K.; Supervision: G.T., Ö.P.; Fundings: Ö.P.; Materials: Z.Ö., H.Ö.; Data: O.B., G.T. Analysis: Ö.P., O.B.; Literature search: H.Ö., Z.Ö.; Writing: Ö.P., C.E.; Critical revision: O.B., H.Ö. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Beğer T, Yavuzer H. Yaşlılık ve Yaşlılık Epidemiyolojisi. Klin Gelişim 2012;25:1–3. 2. Urwin SC, Parker MJ, Griffiths R. General versus regional anaesthesia for hip fracture surgery: A meta-analysis of randomized trials. Br J Anaesth 2000;84:450–5. 3. Desteli EE, Imren Y, Erdoğan M, Aydagün Ö. Quality of life following treatment of trochanteric fractures with proximal femoral nail versus cementless bipolar hemiarthroplasty in elderly. Clin Investig Med 2015;38:E63–72. 4. Khan SK, Kalra S, Khanna A, Thiruvengada MM, Parker MJ. Timing of surgery for hip fractures: a systematic review of 52 published studies involving 291,413 patients. Injury 2009;40:692–7. 5. Görmeli G, Korkmaz MF, Görmeli CA, Adanaş C, Karataş T, Şimşek SA. Comparison of femur intertrochanteric fracture fixation with hemiarthroplasty and proximal femoral nail systems. Ulus Travma Acil Cerrahi Derg 2015;21:503–8. 6. Langslet E, Frihagen F, Opland V, Madsen JE, Nordsletten L, Figved W. Cemented versus uncemented hemiarthroplasty for displaced femoral neck fractures: 5-year followup of a randomized trial. Clin Orthop Relat Res 2014;472:1291–9. 7. Gölge UH, Pazarci O, Kılınç S, Nusran G, Kaymaz B, Göksel F, et al. The treatment of intertrochanteric fractures comparison of PFN and hemiarthroplasty 3-year mortality study. Acta Orthop Belg 2016;82:508–15. 8. Moja L, Piatti A, Pecoraro V, Ricci C, Virgili G, Salanti G, et al. Timing matters in hip fracture surgery: patients operated within 48 hours have better outcomes. A meta-analysis and meta-regression of over 190,000 patients. PLoS One 2012;7:e46175. 9. Uzoigwe CE, Burnand HG, Cheesman CL, Aghedo DO, Faizi M, Middleton RG. Early and ultra-early surgery in hip fracture patients improves survival. Injury 2013;44:726–9. 10. Lee DJ, Elfar JC. Timing of Hip Fracture Surgery in the Elderly. Geriatr Orthop Surg Rehabil 2014;5:138–40. 11. Orces CH. Epidemiology of hip fractures in Ecuador. Rev Panam Salud Pública 2009;25:438–42. 12. Cooper C, Campion G, Melton LJ 3rd. Hip fractures in the elderly: a world-wide projection. Osteoporos Int 1992;2:285–9.

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Ekici et al. Effect on mortality of treatment method and surgery time for hip fracture patients aged over 65 years 13. Roche JJ, Wenn RT, Sahota O, Moran CG. Effect of comorbidities and postoperative complications on mortality after hip fracture in elderly people: prospective observational cohort study. BMJ 2005;331:1374. 14. Keene GS, Parker MJ, Pryor GA. Mortality and morbidity after hip fractures. BMJ 1993;307:1248–50. 15. Schnell S, Friedman SM, Mendelson DA, Bingham KW, Kates SL. The 1-year mortality of patients treated in a hip fracture program for elders. Geriatr Orthop Surg Rehabil 2010;1:6−14. 16. Shiga T, Wajima Z, Ohe Y. Is operative delay associated with increased mortality of hip fracture patients? Systematic review, meta-analysis, and meta-regression. Can J Anaesth 2008;55:146–54. 17. Forni C, Gazineo D, D’Alessandro F, Fiorani A, Morri M, Sabattini T, Ambrosi E, et al. Predictive factors for thirty day mortality in geriatric patients with hip fractures: a prospective study. Int Orthop 2019;43:275−81. 18. Paksima N, Koval KJ, Aharanoff G, Walsh M, Kubiak EN, Zuckerman JD, et al. Predictors of mortality after hip fracture: a 10-year prospective study. Bull NYU Hosp Jt Dis 2008;66:111–7. 19. Kenzora JE, McCarthy RE, Lowel JD, Sledge CB. Hip Fracture Mortality. Clin Orthop Relat Res 1984;186:45–56. 20. Sasabuchi Y, Matsui H, Lefor AK, Fushimi K, Yasunaga H. Timing of surgery for hip fractures in the elderly: A retrospective cohort study. Injury 2018;49:1848–54. 21. Al-Ani AN, Samuelsson B, Tidermark J, Norling A, Ekström W, Cederholm T, et al. Early operation on patients with a hip fracture improved the ability to return to independent living. A prospective study of 850 patients. J Bone Joint Surg Am 2008;90:1436–42. 22. Ravikumar KJ, Marsh G. Internal fixation versus hemiarthroplasty versus total hip arthroplasty for displaced subcapital fractures of femur--13 year results of a prospective randomised study. Injury 2000;31:793–7. 23. Khan RJK, MacDowell A, Crossman P, Keene GS. Cemented or uncemented hemiarthroplasty for displaced intracapsular fractures of the hip - A systematic review. Injury 2002;33:13–7.

24. Partanen J, Syrjälä H, Vähänikkilä H, Jalovaara P. Impact of deep infection after hip fracture surgery on function and mortality. J Hosp Infect 2006;62:44–9. 25. Talmaç MA, Görgel MA, Armağan R, Sönmez MM, Özdemir HM. Examining implant superiority in the treatment of simple pertrochanteric fractures of the proximal femur in elderly patients. Ulus Travma ve Acil Cerrahi Derg 2019;25:410–6. 26. Çelik H, Kara A, Sağlam Y, Türkmen İ, Aykut S, Erdil M. Can double fluoroscopy in the oblique position reduce surgical time and radiation exposure during intertrochanteric femur fracture nailing? Ulus Travma ve Acil Cerrahi Derg 2018;24:581–6. 27. Zehir S, Şahin E, Zehir R. Comparison of clinical outcomes with three different intramedullary nailing devices in the treatment of unstable trochanteric fractures. Ulus Travma ve Acil Cerrahi Derg 2015;21:469– 76. 28. Uzer G, Elmadağ NM, Yıldız F, Bilsel K, Erden T, Toprak H. Comparison of two types of proximal femoral hails in the treatment of intertrochanteric femur fractures. Ulus Travma ve Acil Cerrahi Derg 2015;21:385–91. 29. Kaynak G, Ünlü MC, Güven MF, Erdal OA, Tok O, Botanlıoğlu H, et al. Intramedullary nail with integrated cephalocervical screws in the intertrochanteric fractures treatment: Position of screws in fracture stability. Ulus Travma ve Acil Cerrahi Derg 2018;24:268–73. 30. Uysal Aİ. The effect 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. Turkish J Trauma Emerg Surg 2019;26:109–14. 31. Karaman Ö, Özkazanlı G, Orak MM, Mutlu S, Mutlu H, Çalışkan G, et al. Factors affecting postoperative mortality in patients older than 65 years undergoing surgery for hip fracture.Ulus Travma ve Acil Cerrahi Derg 2015;21:44–50. 32. Richmond J, Aharonoff GB, Zuckerman JD, Koval KJ. Mortality risk after hip fracture. J Orthop Trauma 2003;17:53–6.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Altmış beş yaş üstü kalça kırığı olgularında tedavi yöntemi ve ameliyata alınma zamanının mortaliteye etkisi Dr. Cihat Ekici, Dr. Özhan Pazarcı, Dr. Seyran Kılınç, Dr. Zekeriya Öztemür, Dr. Hayati Öztürk, Dr. Gündüz Tezeren, Dr. Okay Bulut Cumhuriyet Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Sivas

AMAÇ: Sunulan çalışmada 65 yaş üstündeki kalça kırığı nedeni ile ameliyat edilen hastalarda implant çeşidi ve cerrahi zamanlamanın mortaliteye etkisinin değerlendirilmesi amaçlandı. GEREÇ VE YÖNTEM: Altmış beş yaş üstü 301 hasta incelendi. Hastalar Grup 1 çimentolu hemiartroplasti, Grup 2 çimentosuz hemiartroplasti ve Grup 3 femur proksimal çivi yapılanlar olarak ayrıldı. Ameliyat zamanı, kırık ve demogrofik bilgileri geriye dönük kaydedildi. BULGULAR: Bilgilerine ulaşılamayan 59 hasta çıkarıldıktan sonra çalışmaya 242 hasta dahil edildi. Hastaların ortalama yaşı 80.5 (65–100) idi. Tedavi yöntemine göre hasta gruplarına bakıldığında; Grup 1 (n=146) %60.3, Grup 2 (n=54) %22.3, Grup 3 (n=42) %17.4. İlk 48 saate opere edilenlerle, sonrasında opere edilenler arasında anlamlı bir fark bulunmadı (p=0.834). Tedavide implant seçiminin survey üzerine etkisi vardı (p=0.016). Çimentolu hemiartroplasti yapılan hastaların surveyinin çimentosuz hemiartroplasti ve proksimal femoral çivi (PFN) yapılanlara göre daha uzun olduğu görüldü. TARTIŞMA: Her üç grupta da ilk 48 saatte ameliyata alınmamanın mortalite üzerinde anlamlı etkisinin olmadığı görüldü. Bunun yanında yaş ve cinsiyet mortalite üzerine etkilidir. Ayrıca implant seçimide mortaliteyi etkilemektedir. Anahtar sözcükler: Ameliyat zamanı; hemiarthroplasti; kalça kırığı; mortality; proksimal femoral nail Ulus Travma Acil Cerrahi Derg 2020;26(3):439-444

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ORIGIN A L A R T IC L E

Effects of different anesthesia techniques on intraoperative blood loss in acetabular fractures undergoing the Modified Stoppa approach Ahmet Emrah Açan, M.D.,1 Cem Yalın Kılınç, M.D.,1 Emre Gültaç, M.D.,1 Başak Altıparmak, M.D.,2 Ali İhsan Uysal, M.D.,2 Nevres Hürriyet Aydoğan, M.D.1 1

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

2

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

ABSTRACT BACKGROUND: This study aims to evaluate the effects of the anesthesia technique on the intraoperative blood loss in acetabular fracture patients undergoing the Modified Stoppa approach. METHODS: We retrospectively identified 63 patients who underwent a Modified Stoppa approach for acetabular fracture from January 2014 to July 2018. A total of 20 patients were excluded from this study for the following reasons: bilateral acetabular fractures (n=6), undergoing antiaggregant treatment (n=3), incomplete anesthesia records (n=3), emergency pelvic surgery due to hemodynamic instability (n=5), splenic rupture (n=2), and liver laceration (n=1). The patients were divided into two groups as follows: patients undergoing general anesthesia (GA) (n=22) and patients undergoing combined epidural-general anesthesia (CEGA) (n=21). The main outcome measurements studied were the intraoperative blood loss and the need for intraoperative and/or postoperative blood transfusions. RESULTS: No statistically significant differences were found between the groups concerning the age, gender, type of fracture, mechanism of injury, time from injury to surgery, Injury Severity Score, associated injuries, and comorbidities (p>0.05). The mean intraoperative blood losses were 717.27 ml (300–1.600 ml) in the GA group and 473.81 ml (150–1.020 ml) in the CEGA group (p<0.001). In the cases with only an isolated acetabular fracture, the intraoperative blood transfusion means were 2.43 units (1–5 units) in 14 patients in the GA group and 1.27 units (1–4 units) in 15 patients in the CEGA group (p<0.001). CONCLUSION: Less intraoperative bleeding was seen in those patients undergoing CEGA when compared to those undergoing GA. This is a significant advantage for acetabular surgery, which has a long learning curve and a high risk of bleeding. Keywords: Acetabular fracture; bleeding; blood loss; epidural anesthesia; Stoppa.

INTRODUCTION General anesthesia (GA) is the most frequently used anesthesia method in major orthopedic surgeries.[1] However, in studies related to hip and knee arthroplasty, hip fractures, and pelvic tumors, the use of epidural anesthesia has been reported to provide several advantages, such as a lower risk of deep vein thrombosis and pulmonary embolism, a decrease in intraoperative blood loss, better postoperative pain control, and a reduction in perioperative complications.[2–8]

Acetabular fractures are usually high-energy traumatic injuries. [9] When carrying out surgery to repair these fractures, a significant amount of bleeding may develop during the approach. Moreover, because these fractures are often accompanied by fractures in other regions, high intraoperative blood loss amounts may be seen.[10] Unfortunately, an intraoperative and/ or postoperative blood transfusion involves risks and complications, such as an allergic reaction, transfusion of the wrong blood group, transfusion of infectious agents, and transfusionrelated down-modulation of the immune system.[11–14]

Cite this article as: Açan AE, Kılınç CY, Gültaç E, Altıparmak B, Uysal Aİ, Hürriyet Aydoğan N. Effects of different anesthesia techniques on intraoperative blood loss in acetabular fractures undergoing the Modified Stoppa approach. Ulus Travma Acil Cerrahi Derg 2020;26:445-452. Address for correspondence: Ahmet Emrah Acan, M.D. Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Muğla, Turkey Tel: +90 252 - 214 13 26 E-mail: dremrahacan@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):445-452 DOI: 10.14744/tjtes.2019.09294 Submitted: 22.02.2019 Accepted: 09.08.2019 Online: 15.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Açan et al. Effects of anesthesia on blood loss in acetabular fractures

Despite several studies in the current literature related to the Modified Stoppa technique and the associated blood losses, there is insufficient information about the relationship between the anesthetic technique and the amount of intraoperative bleeding.[10,15–22] The present study aims to investigate whether or not there was a difference in the intraoperative blood loss between acetabular fracture cases undergoing GA and cases undergoing combined epidural-general anesthesia (CEGA) operated on using the Modified Stoppa technique.

MATERIALS AND METHODS Approval for this study was granted by the Faculty ethics committee. A retrospective evaluation was conducted of patients aged over 18 years old with an acetabular fracture who underwent the Modified Stoppa technique at the Medical Faculty hospital between January 2014 to July 2018. All the medical records were reviewed for the demographic data, Injury Severity Score (ISS), mechanism of injury, number of associated fractures, number of associated medical comorbidities, time from injury to surgery, operation time, and amount of blood lost during the operation. The exclusion criteria were as follows: patients with bilateral acetabular fractures, a preoperative international normalized ratio (INR) value of ≥1.3, receiving anticoagulant/antiaggregant treatment, a platelet count lower than 100.000/mcL or over 450.000/mcL, incomplete anesthesia records, intraoperative iatrogenic major vascular injury, previous surgery with bleeding before orthopedic surgery, an indication for emergency surgery, intraoperative hemodynamic instability, and a known bleeding diathesis, such as chronic liver disease. Anesthesia was administered to all patients by the same two anesthesiologists. In the operating room, standard monitoring was performed with the help of electrocardiography, invasive blood pressure measurements, pulse oximetry, and bi-spectral index monitoring (BIS). All the patients were hemodynamically stable before the operation. For induction of anesthesia, all the patients routinely received 2–3 mg/kg of propofol, 1–2 mcg/kg of fentanyl, and 0.6 mg/kg of rocuronium bromide until the BIS values decreased under 60. The maintenance of anesthesia was provided with 1–2% sevoflurane in 40% O2 + 60% N2O mixture with targeting a BIS ratio between 40–60. In the CEGA group, after induction, the patients were placed in the lateral decubitus position, with the healthy extremity underneath, and an epidural catheter was placed in the L3–L4 interspace using the loss-of-resistance technique. In all the patients in the CEGA group, immediately after the surgical incision, the controlled administration of 9 ml of 0.25% bupivacaine +50 mcg of fentanyl was applied from the epidural catheter. When there was a >20% increase in the intraoperative parameters from the basal values, a dose of 4.5 ml of 0.25% bupivacaine +25 mcg of fentanyl was administered from the epidural catheter in CEGA group and intravenous 0.5 mcg kg-1 fentanyl was administered as a bolus dose in GA group. When there was a >20% reduction in the 446

intraoperative parameters from the basal values, intravenous 5 mg ephedrine was administered as a bolus dose in both groups. For postoperative pain control, the epidural catheter was used for 48 hours, and it was removed at the end of the 2nd postoperative day. Intraoperative blood loss during the Modified Stoppa intervention was recorded using data-linkage to surgical anesthesia records. The anesthesia team calculated intraoperative blood loss by evaluating the number of used small swabs and suction bottle contents. During the surgery, only small swabs were used, and these were collected and counted at the end of the procedure. According to previous literature,[23] each saturated small swab was accepted as containing 60 mL of blood, and the amount of blood aspirated intraoperatively was calculated by subtracting the amount of saline used intraoperatively from the accumulated material in the suction bottle. The amount of intraoperative bleeding was calculated from these two values and recorded routinely by the anesthesia team. The operating time was accepted as the time from the start of the skin incision for the Modified Stoppa technique in the pelvic region to the time of skin closure. An intraoperative transfusion of packed red blood cells was given to those patients with hemoglobin (Hb) levels <8 mg/dL and/or ongoing blood loss. A postoperative transfusion was given to the patients with Hb levels <8 mg/dL and Hb levels <9 mg/dL with signs or symptoms of anemia (i.e., dizziness, shortness of breath, tachypnea, or tachycardia). The intraoperative and postoperative transfused red blood cell numbers were also recorded.

Statistical Analysis All the computational analyses were conducted using the R software for statistical computing. The Welch’s t-test was used to assess the differences between the patients in the two groups in terms of the age, ISS, operation time, and amount of intraoperative blood loss. The summary statistics of the compared values were presented as the mean ± standard deviation. The correlations between the operation time and the amount of blood lost during the operation were calculated using the Pearson correlation coefficient. A p-value of <0.05 was considered to be statistically significant.

RESULTS A total of 20 patients were excluded from this study: Six patients had bilateral acetabular fractures, three patients were taking antiaggregant medications, three patients had incomplete intraoperative anesthesia records, five patients were hemodynamically unstable and required emergency surgery, and two patients with splenic ruptures and one patient with a liver laceration were emergencies that were operated on by the general surgery team. After the implementation of the exclusion criteria, this study included a total of 43 patients Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Açan et al. Effects of anesthesia on blood loss in acetabular fractures

(26 males and 17 females, aged 18–80 years old) who were operated on using the Modified Stoppa technique. The patients were separated into two groups as follows: a GA group (n=22) and a CEGA group (n=21) (Table 1). The mean age of the patients was 38.3 years old (18–70 years) in the GA group and 40.1 years old (19–67 years) in the CEGA group. There were no statistically significant differences between the groups concerning the age, gender, type of fracture, mechanism of injury, ISS, associated injuries, and comorbidities (p>0.05) (Table 1). The ISS means were 13.9 (9–34) in the GA group and 14.7 (10–37) in the CEGA group, with no statistically significant difference between the groups (p>0.05). All the patients were exposed to high-energy trauma. The mechanisms of trauma included being struck by a motor vehicle in 14 cases, a traffic accident within the vehicle in 19 cases, and a fall from a height in 10 cases (Table 1). According to the Judet and Letournel classification, the fractures were as follows: 14 anterior columns, eight transverse columns, 11 both columns, five anterior columns plus posterior hemitransverse, and five T-type fractures.[24] Due to concomitant head trauma in three patients, thoracic injury in three patients,

intra-abdominal pathology in two patients, and fractures in other regions in one patient, a total of nine patients were transferred from the emergency department to the intensive care unit (ICU) for close monitoring. After the clinical stabilization of these patients (mean: 5.6 days, range: 2–11 days), they were transferred to the orthopedics clinic. In eight patients in the GA group and six patients in the CEGA group, there were long bone fractures other than the patients in the pelvic region (Table 1). All the patients were operated on by the same orthopedic surgeon using the Modified Stoppa technique at a mean of 7.1 days (5–14 days) after the initial presentation. The means were 6.95 days (5–12 days) in the GA group and 7.24 days (5–14 days) in the CEGA group. When considering that the patients were clinically stable, the timing of the operation was planned semi-electively. When there was a concomitant fracture, the surgical intervention was conducted on the acetabular fracture first. The mean preoperative Hb values were 12.3 g/dL (10.5–17.1 g/dL) in the GA group and 11.9 (10.2–16.7) in the CEGA group. The mean INR values were 0.91 IU (0.82–1.1 IU) in the GA group and 0.95 IU (0.86–1.15 IU) in the CEGA group.

Table 1. Patient demographic data (n=43)

GA group (n=22)

CEGA group (n=21)

p >0.5

Mean age (years)

38.3

40.1

Male/female

12/10

15/6 >0.5

Mean Injury Severity Score

13.9

14.7

>0.5

Mean hemoglobin

12.3

11.9

>0.5

Mean international normalized ratio Mean platelet count Concomitant fracture

0.91

0.95

>0.5

233.500

256.300

>0.5

8

6

Comorbidities

Diabetes mellitus

2

3

Chronic obstructive pulmonary disease

0

1

Hypertension

5

4

Injury to surgery (days)

6.95

7.24

>0.5

Operating time (minutes)

155.9

148.1

>0.5

Mechanism of injury

Struck by motor vehicle

6

8

Traffic accident inside the vehicle

11

8

Fall from height

5

5

Fracture type*

Anterior column fracture

9

5

Both columns fracture

4

7

Transverse fracture

5

3

Anterior column plus hemitransverse

2

3

T-type fracture

2

3

Judet and Letournel classification. GA: General anesthesia; CEGA: Combined epidural-general anesthesia.

*

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Group 2 patients

200 0

Amount of blood lost during operation time

Amount of blood lost during operation time

Group 1 patients 1800 1600 1400 1200 1000 800 600 400

0

50

100 150 Operation time (minutes)

200

1200 1000 800 600 400 200

250

0

0

50

100 150 200 Operation time (minutes)

250

300

Figure 1. Representation of the amount of blood loss and operation time in group 1 patients.

Figure 2. Representation of the amount of blood loss and operation time in group 2 patients.

The mean preoperative platelet counts were 233.500/mcL (121.000–376.000/mcL) in the GA group and 256.300/mcL (128.000–455.000/mcL) in the CEGA group. No statistically significant differences were determined between the groups concerning the preoperative Hb, INR, and platelet count values (p>0.05). The mean operating time was 155.9 mins (95–230 mins) in the GA group and 148.1 mins (90–240 mins) in the CEGA group, with no statistically significant difference between the groups (p>0.05).

the CEGA group. A statistically significant difference was observed between the two groups (p<0.001) (Table 2).

The mean amount of intraoperative blood loss was 717.27 mL (300–1.600 mL) in the GA group and 473.81 mL (150–1.020 mL) in the CEGA group. The difference between the groups was determined to be statistically significant (p<0.001) (Table 2). In both groups, a strong positive correlation was found between the operation time and the amount of blood lost; however, the correlation was stronger in the GA group (r=0.88, p<0.001) than in the CEGA group (r=0.67, p<0.001) (Figs. 1 and 2). When the amount of blood lost was compared both within and between the groups according to the fracture type, the operation time was longer and the blood loss higher in those patients with T-type, transverse, and anterior column plus hemitransverse fractures when compared to the patients with the other types of fractures (anterior column and both columns) (p<0.001). In the cases with no concomitant fractures and only an isolated acetabular fracture was treated using the Modified Stoppa approach, the intraoperative blood transfusion means were 2.43 units (1–5 units) in 14 patients in the GA group and 1.27 units (1–4 units) in 15 patients in

The postoperative blood transfusion means were 1.82 units (1–4 units) in the GA group and 1.76 units (0–4 units) in the CEGA group. There was no statistically significant difference between the two groups (p>0.05). In the cases with no concomitant fractures and only an isolated acetabular fracture, the postoperative blood transfusion means were 1.64 units (1–3 units) in the GA group and 1.53 units (1–3 units) in the CEGA group. No statistically significant difference was seen between the two groups concerning the postoperative blood transfusion amounts (p>0.05). When the time from operation to discharge was examined, the mean was 6.7 days (4–11 days) in the GA group and 6.3 days (3–9 days) in the CEGA group, with no statistically significant difference between the groups (p>0.05). A mortality follow-up of the patients was conducted until the 90th postoperative day. In the GA group, one patient (80 years old) suffered a cardiac arrest on a postoperative day 37 and died. No statistically significant difference was found between the groups concerning the 90-day mortality rate (p>0.05).

DISCUSSION GA remains the most preferred anesthesia method in major orthopedic surgeries.[1] However, with increased technical

Table 2. Intraoperative bleeding and transfusion amounts Intraoperative bleeding amount (mL)

GA group

CEGA group

p

717.27 (300–1600)

473.81 (150–700)

<0.001

n=22 n=21

Intraoperative blood transfusion in patients with an isolated acetabular fracture (units) *

2.43 (1–5)

1.27 (1–4)

<0.001

n=14 n=15

*In cases with concomitant fractures, this could have changed the requirement for an intraoperative blood transfusion; therefore, only the isolated acetabular fractures were evaluated. GA: General anesthesia; CEGA: Combined epidural-general anesthesia.

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skills, the more frequent clinical use of catheters, and new technological developments, regional anesthesia has become more attractive to surgeons and anesthesiologists.[25,26] There are many studies in the literature that have shown the superiority of epidural anesthesia over general anesthesia, although most of these studies have evaluated the results of total hip and knee arthroplasties.[3,6,7,14,25–28] However, previous studies have reported that reduced intraoperative bleeding is related to the application of epidural anaesthesia.[1,4,5,29] A reduction in blood loss with the use of epidural anesthesia during major surgery was first reported by Moir[30] in 1968. The author explained this reduction by the effects of the sympathetic blockade that develops with epidural anesthesia. The sympathetic blockade is well-known to cause a reduction in peripheral resistance, with a fall in the venous pressure, which results in reduced circulation in the pelvic vessels.[30] However, to our knowledge, none of these studies evaluated the effects of regional anesthesia on bleeding in acetabular fracture surgery using the Modified Stoppa approach. In the current literature, there are some studies that compare general anesthesia (GA) with epidural anesthesia and/or combined regional and general anesthesia (CEGA) concerning bleeding in orthopaedic surgeries.[1,4,5,31] Strauss et al.[1] and Dauphin et al.[4] compared to GA and CEGA groups. Dauphin et al.[4] operated on 37 hip arthroplasty patients using GA in 17 cases and CEGA in 20 cases. The bleeding values were found 1,259.2±366.0 mL in the GA group and 663.8±299.0 mL in the CEGA group. The authors reported that the most possible reason for less intraoperative bleeding in the CEGA group was the sympathetic blockade, as described by Moir previously. In a retrospective study by Strauss et al.,[1] a total of 138 posterior acetabular fracture patients were operated on using the Kocher-Langenbeck approach (64 with GA and 74 with CEGA). The patients were compared concerning the hospital length of stay, postoperative pain control, time to mobilization with physical therapy, and intraoperative blood loss. No differences were reported between the groups concerning the length of stay, pain score, or time to rehabilitation. Although not highly clinically significant, a statistically significant difference was determined in the intraoperative bleeding (458 mL in the CEGA group and 543 mL in the GA group). Similar to Dauphin et al., Strauss et al.[1] reported sympathetic blockade as a possible reason for less blood loss in the epidural group. In another study, Freeman et al.[5] evaluated the effects of anesthesia on the amount of bleeding in intrapelvic tumor surgeries, a total of 174 patients were retrospectively evaluated, with 102 patients administered hypotensive epidural anesthesia and 72 standard GA, to which a hemipelvectomy, sacrectomy, or hindquarter amputation was applied. The blood loss was 1.457 mL (1.114–1.801 mL) in the hypotensive epidural anesthesia group and 2.421 mL (1.877– 2.965 mL) in the GA group. The intraoperative mean arterial pressures were also lower in the epidural group throughout the operation. In this study, the authors suggested that less blood loss in the epidural group was not only related to the Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

sympathetic blockade but also lower intraoperative mean arterial pressures (MAP). However, in the study of Strauss et al.,[1] intraoperative MAP changes were similar between the groups. The authors reported that the possible mechanism of less blood loss during their study was independent of hemodynamic changes. In our study, to provide a more standard sample group, we excluded the patients with unstable hemodynamic measurements. When there was a more than 20% increase in heart rate or MAP of the patients, the intraoperative hemodynamic management was performed with epidural administration of bupivacaine+fentanyl in CEGA group and intravenous administration of fentanyl in GA group. The intraoperative MAP measurements were similar between the groups. Consequently, we eliminated the effects of blood pressure on intraoperative bleeding. Yadav et al.,[31] similar to Strauss et al., compared the effects of general anesthesia, regional anesthesia, and combined regional and general anesthesia on the perioperative outcomes of pelvi-acetabular fracture surgeries. They evaluated 59 patients retrospectively and reported intraoperative blood losses of 996.43±549.29 mL in the combined regional and general anesthesia group, 696.67±500.33 mL in the regional anesthesia group, and 870±516.79 mL in the general anesthesia group. Moreover, no significant differences were found between the three groups concerning the length of the hospital stay and duration of surgery, and they concluded that there was no specific significant advantage of this anesthetic technique on the observed perioperative complications in pelvi-acetabular fracture surgeries.[31] However, no detailed information was provided about the surgical approach used, fracture type, how many surgeons performed the surgeries, and method for determining the intraoperative blood loss. In addition, the patient position and approach showed statistical significance among the groups.[31] In the current study, GA or CEGA was administered while using the Modified Stoppa technique in acetabular fracture cases. Epidural anesthesia was not used alone. Because the positioning of a patient with an acetabular fracture for epidural anesthesia administration is a painful procedure, and it is almost impossible for a patient to tolerate this. By positioning the patient laterally after administering GA, the pain associated with the positioning can be overcome, and the placement of the epidural catheter is facilitated, with easier access to the epidural space. Another advantage of performing general anesthesia in both groups is that we presumably eliminated a probable effect of inhaled anesthetics on bleeding. All of the patients received sevoflurane for the maintenance of anesthesia by targeting the same BIS values. However, there were no data concerning the minimum alveolar concentration (MAC) values of sevoflurane overtime on anesthesia records of the patients. In the current study, the intraoperative blood losses were 717.27 mL (300–1.600 mL) in the 22 patients in the GA group and 473.81 mL (150–1.020 ml) in the 21 patients in the CEGA group. The difference between the two groups 449


Açan et al. Effects of anesthesia on blood loss in acetabular fractures

was statistically significant (p<0.001). Strauss et al. concluded that a difference of approximately 100 mL between the GA and CEGA groups in the intraoperative bleeding was unlikely to be of clinical significance in contrast to reports in the literature suggesting that the use of supplemental epidural anesthesia in arthroplasty cases provided a reduction in intraoperative bleeding.[4,32] However, in the present study, the mean difference between the groups was 234 mL and it should be accepted as clinically significant.[4] The surgical approach in Strauss et al.’s[1] study was using the Kocher-Langenbeck incision, which is an extra-pelvic approach, whereas in the present study was Modified Stoppa approach, which is an intrapelvic approach. Another study related to intrapelvic approach by Freeman et al.,[5] mean intraoperative bleeding difference between the hypotensive epidural anesthesia and GA groups in surgeries undergoing intrapelvic approach was 964 mL with clinical significance. However, in that study, intrapelvic tumors were evaluated, not fractures, and the GA was compared to hypotensive epidural anesthesia. On the one hand, this may suggest that in intrapelvic interventions, such as the Modified Stoppa approach, the pelvic vascularity is higher when compared to cases undergoing an extrapelvic approach, such as the Kocher-Langenbeck. Thus, there is a higher risk of bleeding. On the other hand, the use of CEGA when there is a higher potential for bleeding, such as in the intrapelvic approach, has been shown to be advantageous concerning the amount of intraoperative bleeding. In the Strauss et al.’s[1] study, a cell saver machine was used when calculating the intraoperative bleeding amount, and the anesthesiologists estimated the blood loss based on the machine’s recordings. In a previously published arthroplasty series by Freeman et al.,[5] the blood loss was determined indirectly using a formula, including the preoperative and postoperative Hb levels and the number of units of red blood cells transfused[33] It has been advocated that with this method, surgeon or anesthesiologist bias could be avoided, and the amount of blood on the drapes, gowns, and the operating room floor could be overlooked with other methods.[5] In the present study, the amount of intraoperative bleeding was determined from the small swab count and suction bottle contents values that were recorded by the anesthesia team. With this method, and with the Modified Stoppa approach being performed in the supine position, it is believed that the amount of blood on the drapes, gowns, and operating room floor was not of a degree to affect the measurement. In addition, because the pelvic surgery was applied first to those patients with a concomitant fracture, only the amount of intraoperative blood lost when using the Modified Stoppa approach could be calculated. When the current literature is examined, it can be seen that many studies have provided mean operating times.[1,4,5,10,15– 22,28,29] However, to our knowledge, there is not any study in the literature that showed a direct relationship between an increased operating time and an increased blood loss. In 450

the present study, the operating times of the patients that were given GA and CEGA were 156 mins and 148 mins, respectively, with no statistically significant difference between the groups (p=0.544). Again, in both groups, the operating times of the patients with T-type, both column, and anterior column plus hemitransverse fractures were longer than the operating times of the patients with the other types of fractures, and the amount of bleeding was higher (p<0.001). Thus, it can be said that when the fracture type is more complicated, the operating time is prolonged, and the amount of blood loss is increased. Controlled hypotension, autologous blood transfusion, intra-operative blood salvage, and the use of erythropoietin and antifibrinolytic agents are other described blood conserving techniques to reduce blood loss and post-operative transfusion rate, similar to the aim of this study.[34,35] The antifibrinolytics include aprotinin, epsilon-aminocaproic acid and tranexamic acid (TXA). Among them, TXA has attracted the most attention. However, its use is controversial in orthopaedic trauma patients due to its theoretical risk of increased thromboembolic complications. However, Gausden et al.[36] reported a systematic review and meta-analysis concluded that tranexamic acid reduced the risk of blood transfusion, reduces perioperative blood loss, and had no significant effect on the risk of symptomatic thromboembolic events. Sukeik et al.[37] and Alshryda et al.[38] reported systematic review and meta-analysis of the use of TXA in total knee replacement and total hip replacement respectively. They reported reduced blood loss using 104 mL and 591 mL in total hip replacement and total knee replacement, respectively. Additionally, no increased risk of deep vein thrombosis and pulmonary embolism was reported due to TXA use both in total knee and hip replacement surgeries. In this study, we did not evaluate the effects of TXA on blood loss in acetabular fracture patients undergoing the Modified Stoppa approach. However, it would not be wrong to foresee that TXA would potentiate the reduction in the blood loss effects of CEGA. A major limitation of this study was that this study was retrospective, and therefore prone to various forms of bias (selection bias and recall bias). Besides, retrospective evaluation of the calculation of the intraoperative blood loss may lead to a question mark about the reliability of this study. However, in our clinic, anesthesia team determines the intraoperative blood loss by evaluating the number of used saturated of small swabs and suction bottle contents and records the amount of intraoperative blood loss to the patient anesthesia form as a daily routine practice. In addition, the number of patients was relatively low. In a broader patient group, potential differences could be revealed according to the fracture type. A further limitation of this study was that the pain scores were not recorded. Thus, pain control could not be evaluated. If there had been such an evaluation, the effects of the epidural analgesia during the postoperative period concerning the pain and reducing the opioid-induced side-effects Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Açan et al. Effects of anesthesia on blood loss in acetabular fractures

(thereby providing earlier postoperative rehabilitation and shortening the postoperative length of the hospital stay), as have been reported in total hip and knee arthroplasty cases in the literature, might have been similar to those in the acetabular fractures undergoing Modified Stoppa surgery.[39,40] However, Strauss et al.[1] found no difference between the patients administered CEGA or GA for acetabular posterior wall fractures about the length of stay, postoperative pain scores, or time to rehabilitation, but they stated that larger patient populations were required. As mentioned before, we had no date concerning the MAC values of sevoflurane overtime on anesthesia records of the patients. Unfortunately, we could not assess the effects of MAC values on intraoperative bleeding in this study. The major strengths of this study were the homogeneity between the groups, and that the surgeries were carried out by the same surgeon in all the cases. In the study by Strauss et al.,[1] the operation was performed by one of 10 faculty orthopedic traumatologists, and the type of anesthesia used was determined by one of 18 faculty anesthesiologists for each procedure. Therefore, the anesthesiologists may have exhibited a selection bias in preferring the CEGA over GA for the patients at a higher risk of intraoperative blood loss and decreased postoperative mobility. In the study by Freeman et al.,[5] the anesthetic technique used was primarily determined by the anesthesiologist, and it lacked randomization. Similarly, in the present study, the type of anesthesia used was determined by the same two anesthesia specialists, who may have also exhibited selection bias.

Conclusion In the acetabular fracture cases in which the Modified Stoppa technique was used, less intraoperative bleeding was seen in the patients administered CEGA when compared to the patients administered GA. This is a significant advantage for acetabular surgeries, which has a long learning curve and a high risk of bleeding. In further prospective, randomized, controlled trials with larger patient populations, higher benefits can be obtained by not concentrating on the amount of bleeding, but by conducting a more comprehensive evaluation concerning the other benefits of the technique and its perioperative complications. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.E.A, C.Y.K., B.A.; Design: A.E.A, C.Y.K., B.A.; Supervision: C.Y.K., B.A.; Materials: B.A., A.İ.U.; Data: B.A., A.İ.U.; Analysis: A.E.A., B.A.; Literature search: A.E.A., E.G., B.A.; Writing: A.E.A., B.A.; Critical revision: N.H.A. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

has received no financial support.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Modifiye Stoppa yaklaşımı ile ameliyat edilen asetabulum kırıklarında farklı anestezi tekniklerinin intraoperatif kan kaybı üzerine etkisi Dr. Ahmet Emrah Açan,1 Dr. Cem Yalın Kılınç,1 Dr. Emre Gültaç,1 Dr. Başak Altıparmak,2 Dr. Ali İhsan Uysal,2 Dr. Nevres Hürriyet Aydoğan1 1 2

Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Muğla Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Anestezi ve Reanimasyon Anabilim Dalı, Muğla

AMAÇ: Asetabulum kırığı nedeniyle Modifiye Stoppa yaklaşımı ile ameliyat edilen hastalardaki intraoperatif kanama miktarına, anestezi tekniğinin etkisini değerlendirmektir. GEREÇ VE YÖNTEM: Ocak 2014 ve Temmuz 2018 tarihleri arasında asetabulum kırığı nedeniyle Modifiye Stoppa yaklaşımı ile ameliyat edilen 63 hasta geriye dönük olarak değerlendirildi. İki taraflı asetabulum kırığı (n=6), antiagregan tedavisi (n=3), anestezi kayıtlarında eksiklik (n=3), hemodinamik instabilite nedeniyle acil pelvik cerrahi geçirmiş (n=5), dalak yırtığı (n=2) ve karaciğer yırtığı (n=1) olan, toplam 20 hasta çalışmadan dışlandı. Hastalar genel anestezi yapılanlar (GA) (n=22) ve kombine epidural-genel anestezi yapılanlar (CEGA) (n=21) olmak üzere iki gruba ayrıldı. İntraoperatif kanama miktarı ve intraoperatif ve/veya ameliyat sonrası kan transfüzyon ihtiyacı, değerlendirilen ana ölçüm parametreleriydi. BULGULAR: Gruplar arasında yaş, cinsiyet, kırık tipi, yaralanma mekanizması, yaralanma ile cerrahi arasındaki süre, yaralanma şiddet skoru, eşlik eden yaralanmalar ve komorbiditeler açısından istatistiksel anlamlı fark yoktu (p>0.05). Ortalama intraoperatif kanama miktarı GA grubunda 717.27 ml (300–1.600 ml) ve CEGA grubunda 473.81 ml (150–1.020 ml) bulundu (p<0.001). İzole asetabulum kıırğı olan olgularda ise, intraoperatif kan transfüzyon ortalaması, GA grubundaki 14 hastada 2.43 ünite (1–5 ünite) ve CEGA grubundaki 15 hastada 1.27 ünite (1–4 ünite) bulundu (p<0.001). TARTIŞMA: CEGA yapılan hastalarda, GA yapılan hastalara göre daha az intraoperatif kanama görüldü. Bu, uzun öğrenme eğrisi ve yüksek kanama riski olan asetabulum cerrahi için önemli bir avantajdır. Anahtar sözcükler: Asetabulum kırığı; epidural anestezi; kan kaybı; kanama; Stoppa. Ulus Travma Acil Cerrahi Derg 2020;26(3):445-452

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ORIGIN A L A R T IC L E

Associations between initial injury severity in acute hand, wrist or forearm injuries and disability ratings and time to return to work Sercan Çapkın, M.D., Eralp Erdoğan, M.D.,

Ali Cavit, M.D., Kutay Yılmaz, M.D., Tufan Kaleli, M.D.

Department of Orthopaedics and Traumatology, Division of Hand Surgery, Uludağ University Faculty of Medicine, Bursa-Turkey

ABSTRACT BACKGROUND: This study aimed to examine the relationships between the initial anatomic severity of hand, wrist and forearm injuries, as evaluated by the Modified Hand Injury Severity Score (MHISS), and each of the following parameters: disability rating and time to return to work. METHODS: In this study, 94 patients who underwent operations due to acute hand, wrist and forearm injuries were included. MHISS was used to assess the severity of the injury. Disability rates of the patients were calculated six months after injury in accordance with the ‘Regulation on Disability Criteria, Classification and Health Board Reports to be Given to Disabled People’. The time to return to work was defined as the length of time (in days) between the injury and the patient’s return to work. Spearman rank correlation analysis was performed to analyse correlations between the MHISS and each of the following: disability rates and time to return to work. RESULTS: The mean overall MHISS was 125.23 (5–880). The mean overall upper extremity disability ratio (UEDR) was 17.64±22.6 (range: 0–94), and the mean overall total body disability ratio (TBDR) was 10.57±13.45 (range: 0–56). Among the study population, 87 (92.6%) patients were able to return to their jobs. The mean overall time to return to work was 138.69 (range: 35–365 days). A statistically significant correlation was found between MHISS and UEDR, TBDR and time to return to work and UEDR, TBDR (p<0.001). CONCLUSION: As a result, as the initial injury severity increased, greater disability remained and the time to return to work increased. Predicting prognosis by determining the injury severity in the initial evaluation of patients may be important in predicting a patient’s future permanent disability level, which can contribute to maintaining patient expectations at a reasonable level, thereby aiding in psychosocial support. Keywords: Disability ratings; MHISS; severity of injury; time to return to work.

INTRODUCTION Hand injuries constitute a substantial proportion of all injuries. They may cause long-term physical and functional disabilities, as well as a serious economic effect on employmen. [1,2] The Hand Injury Severity Score (HISS) was developed by Campbell and Kay to investigate the extent of injuries and likely outcomes.[3] The Modified Hand Injury Severity Score (MHISS) was developed later since the original HISS is specific for hand injuries distal to the carpal bones. The MHISS

includes injuries both distal and proximal to the carpal bones up to the elbow level.[4] After the injury, it is important to determine the patient’s recovery time, when the patient can return to work, and whether there is a permanent disability. The HISS and MHISS have been used in various studies to assess various consequences of a hand injury, such as injury pattern, functional outcome, when the patient can return to work, workers’ compensation in industrial injuries, injury-related economic

Cite this article as: Çapkın S, Cavit A, Yılmaz K, Erdoğan E, Kaleli T. Associations between initial injury severity in acute hand, wrist or forearm injuries and disability ratings and time to return to work. Ulus Travma Acil Cerrahi Derg 2020;26:453-461. Address for correspondence: Sercan Çapkın, M.D. Uludağ Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, El Cerrahisi Bilim Dalı, 16059 Bursa, Turkey Tel: +90 224 - 295 00 00 E-mail: sercancapkn@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):453-461 DOI: 10.14744/tjtes.2019.40524 Submitted: 12.02.2019 Accepted: 06.08.2019 Online: 13.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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costs and whether there is permanent disability.[3–14] In most studies, the HISS has been correlated with time to return to work, functional outcome and healing time. A previous study showed a statistically significant correlation between the HISS score and the American Medical Association (AMA) impairment rating, evaluated by loss of active movement.[2] In Turkey, patients’ disability ratings are determined as percentages (%) based on the ‘Regulation on Disability Criteria, Classification and Health Board Reports to be Given to Disabled People’.[15] To our knowledge, the relationship between MHISS and disability ratings has not been evaluated in a population of patients in Turkey.

overall MHISS comprised the total of the scores for integument, skeletal, motor and neurovascular components. The MHISS was grouped into four grades: minor (≤20), moderate (21–50), severe (51–100) and major (≥101).

This study aimed to examine the relationships between the initial anatomic severity of hand, wrist and forearm injuries, as evaluated by the MHISS, and each of the following parameters: disability rating and time to return to work.

Measurement of Disability Ratings

MATERIALS AND METHODS

1. To calculate the disability rate for any finger, all pathologies in the finger (e.g., amputation, loss of sensation and limitation of movement) were combined. The Balthazard formula was used to combine two or more degrees of disability.[15]

This retrospective study was approved by the Clinical Research Ethics Committee of the Bursa Uludağ University Faculty of Medicine (Approval no: 2019-2/9). Between August 2017 and October 2018, 94 patients who underwent operations in our hospital due to acute hand, wrist and forearm injuries were included in this study. The inclusion criteria for this study were as follows: patients were 18 to 65 years of age at the time of injury; patients were employed full-time before the injury; at least six months passed since their injuries and all patients were clinically stable, no longer requiring splinting devices. The exclusion criteria for this study were any of the following: patients had injuries proximal to the forearm; patients had bilateral injuries; patients had concomitant injuries other than hand injury; patients had a previous history of severe hand and forearm injuries and patients’ records had insufficient detail regarding the injury. The patients’ demographic characteristics were recorded, including their age, sex, injured side and dominant side. Each injury’s aetiology was classified into one of six categories: work accidents, traffic accidents, home accidents, gunshot injuries, assault and self-inflicted injuries. The pre-injury occupational category, which depended on the physical characteristics of the job, were categorised into two major groups: white-collar and blue-collar workers. Blue-collar jobs were defined as hard manual labour, whereas white-collar jobs were defined as office work. Furthermore, blue-collar workers were classified into four subcategories: construction workers, textile workers, mechanic/repair worker and others. Injury data were collected from patient records, including photographs of the injury in the operating room, notes of the intraoperative findings and radiographs of the injury. The MHISS was calculated using these data. In the MHISS, integument, skeletal, motor (tendons and muscles) and neurovascular structures were assessed and graded individually. Furthermore, each injured structure was rated in an absolute and weighted manner. The 454

Patient outcomes were evaluated by calculating disability rates after six months of injury. The upper extremity and total body disability ratio of patients were calculated in accordance with the ‘Regulation on Disability Criteria, Classification and Health Board Reports to be Given to Disabled People’.[15] The disability ratio was calculated by an experienced orthopaedic surgeon who had previously served on the Health Board.

The following evaluation procedures were used to assess injured patients’ disability ratings when they reached final stable conditions:

2. Disability values for each individual finger were combined, and the percentage of total hand disability was calculated. 3. The percentage of hand disability was then converted to upper extremity disability using a standard conversion table provided within the regulation. 4. Finally, the percentage of upper extremity disability was converted to total body disability using a standard conversion table provided in the regulation. Before the injury, all the patients were employed full-time. The patients’ times to return to work were noted in post-injury records. The time to return to work was defined as the length of time (in days) between the injury and the patient’s return to work. Statistical analysis was performed using SPSS version 20.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics recorded were mean, standard deviation, minimum/maximum values and percentage. Non-parametric data analyses were performed using the Kruskal–Wallis and Mann–Whitney U tests. Spearman rank correlation analysis was performed to analyse correlations between the MHISS and each of the following: disability rates and time to return to work. All tests were two-sided, and p-values of less than 0.05 were considered statistically significant. The most important results are shown in the accompanying tables and figures.

RESULTS Based on our inclusion criteria, 94 patients were included in this study, all of whom had undergone operations at our Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


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clinic due to hand, wrist or forearm trauma. Among these 94 patients, 23 (24.5%) were female and 71 (75.5%) were male. The patients’ mean age was 38.21±12.95 (range: 18–64) years. There were 46 (48.9%) patients with a right-sided injury and 48 (51.1%) with a left-sided injury. Dominant-side injuries were present in 49 (52.1%) patients, while non-dominant-side injuries were present in 45 (47.9%) patients. The aetiologies of the injuries were work accidents in 49 (52.1%) patients, traffic accidents in 12 (12.8%) patients, home accidents in 11 (11.7%) patients, gunshot injuries in four (4.3%) patients, assaults in six (6.4%) patients and self-inflicted injuries in 12 (12.8%) patients. Anatomically, there were three injured regions: the hand was injured in 50 (53.19%) patients, the wrist was injured in 18 (19.14%) patients and the forearm was injured in eight (8.51%) patients, and the remaining patients had combined hand, wrist and forearm injuries [hand and wrist in seven (7.44%) patients; wrist and forearm in five (5.31%) patients and hand, wrist and forearm in six (6.38%) patients]. According to the pre-injury occupational category, 45 (47.9%) of the patients were white-collar workers, whereas 49 (52.1%) patients were blue-collar workers [10 (10.6%) were construction workers, 17 (18.1%) patients

were textile workers, 13 (13.8%) patients were mechanic/ repair workers and 9 (9.6%) patients were other workers]. The mean overall MHISS was 125.23 (5–880). Based on the MHISS values, four injury grades were present: grade 1 (minor) included 28 (29.8%) patients with a mean MHISS of 14.39±5.74; grade 2 (moderate) included 19 (20.2%) patients with a mean MHISS of 38.89±7.55; grade 3 (severe) included 22 (23.4%) patients with a mean MHISS of 73.05±15.78 and grade 4 (major) included 25 (26.6%) patients with a mean MHISS of 360.92±273.83. The distributions of the patients, according to grades of MHISS for demographic variables (e.g., sex, injured side and dominant/non-dominant-sided injuries), are shown in Tables 1–3. Minor injuries were more common in women; major injuries were more common in men (p<0.01). There were no significant relationships between MHISS grade and injured side or dominant/non-dominant-sided injuries (p>0.05). The patient distribution and mean MHISS values according to the aetiology of injuries are shown in Table 4. The difference

Table 1. Sex distribution of the patients according to grade of MHISS Sex

Minor

Moderate

Severe

Major

Total

n % n % n % n % n %

Female 10 43.5 9 39.1 2 8.7 2 8.7 23 24.5 Male

18 25.4 10 14.1 20 28.2 23 32.4 71 75.5

(χ2: 13.8; p<0.01). MHISS: Modified Hand Injury Severity Score.

Table 2. Injured side distribution of the patients according to grade of MHISS Side

Minor

Moderate

Severe

Major

Total

n % n % n % n % n %

Right 13 28.3 6 13 13 28.3 14 30.4 46 48.9 Left

15 31.3 13 27.1 9 18.8 11 22.9 48 51.1

(χ2: 3.8; p>0.05). MHISS: Modified Hand Injury Severity Score.

Table 3. Dominant/non-dominant side distribution of the patients according to grade of MHISS Dominant hand affected

Minor

Moderate

Severe

Major

Total

n % n % n % n % n %

Yes

15 33.3 12 26.7 7 15.6 11 24.4 49 52.1

No

13 26.5 7 14.3 15 30.6 14 28.6 45 47.9

(χ2: 4.6; p>0.05). MHISS: Modified Hand Injury Severity Score.

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Table 4. Patient distribution, mean MHISS values and disability ratings according to the aetiology of injuries Aetiology of injuries

n

%

MHISS±SD

UEDR%±SD

TBDR%±SD

Work accident

49

52.1

181.04±258.342

24.41±28.29

14.59±16.829

Traffic accident

12

12.8

53±70.378

8.92±10.049

5.42±6.097

Home accident

11

11.7

20.55±12.16

3.45±2.697

2.09±1.446

Gunshot injury

4

4.3

133±42.755

22.75±6.292

13.75±3.594

Assault

6 6.4 61.83±72.35 11.17±12.416 6.83±7.574

Self inflicting injury

12

Total

94 100 125.23±200.566 17.64±22.603 10.57±13.451

12.8

94.67±84.506

13.25±9.845

7.92±5.775

MHISS: Modified Hand Injury Severity Score; UEDR: Upper extremity disability ratio; TBDR: Total body disability ratio; SD: Standard deviation.

Table 5. Patient distribution, mean MHISS values and disability ratings according to pre-injury occupational category Pre-injury occupational category

n

%

MHISS±SD

UEDR%±SD

TBDR%±SD

White collar workers

45

47.9

36.78±45.418

6.71±7.2

4.11±4.318

Blue collar workers

49

52.1

206.47±248.95

27.67±26.974

16.51±16.073

Construction workers

10

10.6

428.4±302.972

50.3±32.239

30±19.195

Textile workers

17

18.1

175.53±223.967

24.76±25.791

14.82±15.323

Mechanic/repair workers

176.69±229.425

24.54±24.48

14.69±14.585

13

13.8

Others

9

9.6

Total

94 100 125.23±200.566 17.64±22.603 10.57±13.451

61.33±24

12.56±6.002

7.33±3.64

MHISS: Modified Hand Injury Severity Score; UEDR: Upper extremity disability ratio; TBDR: Total body disability ratio; SD: Standard deviation.

between the aetiology of injuries and the mean MHISS values was found to be statistically significant (χ2: 21.46, p=0.001). The mean MHISS value was higher in work accidents than in traffic and home accidents, and the differences were statistically significant (p-values were 0.017 and 0.000, respectively). The mean MHISS value was higher in gunshot injuries than in traffic and home accidents, and the differences were statistically significant (p-values were 0.02 and 0.004, respectively). The mean MHISS value was higher in self-inflicting injury than in home accidents, and the difference was statistically significant (p=0.019). The patient distribution and mean MHISS values according to the pre-injury occupational category are shown in Table 5. The difference between the pre-injury occupational category and the mean MHISS values was found to be statistically significant. The mean MHISS value was higher in blue-collar workers than in white-collar workers, and the difference was statistically significant (χ2: 45.937, p<0.001). The mean MHISS value was higher in construction workers than in other bluecollar workers (textile, mechanic/repair and others), and the differences were statistically significant (p-values were 0.006, 0.007 and 0.001, respectively). The mean overall upper extremity disability ratio (UEDR) was 17.64±22.6 (range: 0–94), and the mean overall total 456

body disability ratio (TBDR) was 10.57±13.45 (range: 0–56). Based on MHISS categories, UEDR and TBDR means were statistically different (p<0.001). Table 6 shows the disability rating after subdivision into different MHISS categories. The patient distribution and disability ratings, according to the aetiology of injuries, are shown in Table 4. The difference between the aetiology of injuries and the mean UEDR and TBDR values were found to be statistically significant (p<0.01). The mean UEDR and TBDR values were higher in work accidents than in traffic and home accidents, and the differences were statistically significant (p<0.05). The mean UEDR and TBDR values were higher in gunshot injuries than in traffic and home accidents, and the differences were statistically significant (p<0.05). The mean UEDR and TBDR values were lower in home accidents than in assault and self-inflicting injuries, and the differences were statistically significant (p<0.05). The patient distribution and disability ratings, according to the pre-injury occupational category, are shown in Table 5. The difference between the pre-injury occupational categories and the mean UEDR and TBDR values were found to be statistically significant (p<0.01). The mean UEDR and TBDR values were higher in blue-collar workers than in white-collar workers, and the differences were statistically significant Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Çapkın et al. Associations between MHISS and disability ratings/return to work

Table 6. Disability ratings and time to return to work according to grade of MHISS MHISS

UEDR % (range)

TBDR % (range)

Time to return to work (days)

Minor

3.14 (0–8)

2 (0–5)

47.25 (35–62)

Moderate

7.68 (2–13)

4.58 (1–8)

107.58 (72–150)

Severe

13.32 (2–22)

8 (1–13)

177.27 (120–256)

Major

45.24 (18–94)

27 (11–56)

266.61 (180–365)

Total

17.64 (0–94)

10.57 (0–56)

138.69 (35–365)

p<0.001

p<0.001

p<0.001

Kruskal–Wallis test

MHISS: Modified Hand Injury Severity Score; UEDR: Upper extremity disability ratio; TBDR: Total body disability ratio.

Table 7 . Statistical relationships between variables Spearman rank order method (correlation coefficient)

MHISS

UEDR

TBDR

Time to return to work

Age

MHISS

1.000 0.942* 0.936* 0.981* 000

UEDR 0.942* 1.000 0.999* 0.908* -0.059 TBDR 0.936* 0.999* 1.000 Time to return to work

0.900* -0.060

0.981 0.908 0.900 1.000 0.021 *

*

*

Age

000 -0.059 -0.060

N

94 94 94

0.021 87

1.000 94

Correlation is significant at the 0.01 level (2-tailed). MHISS: Modified Hand Injury Severity Score; UEDR: Upper extremity disability ratio; TBDR: Total body disability ratio.

*

Among the study population, 81 (86.2%) patients were able to return to their jobs without any job modification, whereas six (6.4%) returned to work at the same company with a job change. Seven (7.4%) patients who were not able to return to work were injured after an occupational accident and belonged to the group of blue-collar workers before the injury, of which four were construction workers, two were textile workers and one was a mechanic/repair worker. The time to return to work was noted, except for seven (7.4%) patients who did not return to their previous place of employment. These patients exhibited MHISS grade 4 (major injury), with a mean MHISS of 738±207.13 (range: 420–880), mean UEDR of 85.14±15.99 (range: 54–94) and mean TBDR of 50.71±9.56 (range: 32–56). The time to return to work for each MHISS grade of injury is shown in Table 6. Based on MHISS categories, the average times to return to work were statistically different (p<0.001). The average time to return to work was longer in blue-collar workers than in whitecollar workers, and the difference was statistically significant (p<0.001). Table 7 shows the statistical relationships between variables. We found significant relationships between the MHISS and Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

UEDR, MHISS and TBDR and MHISS and time to return to work. The Spearman rank-order method showed a correlation coefficient of 0.942 between the MHISS and UEDR (Fig. 1); this was statistically significant (p<0.001). The Spearman rank-order method showed a correlation coefficient of 0.936 between the MHISS and TBDR (Fig. 2); this was statistically significant (p<0.001). The Spearman rank-order method

100

Upper extremity disability ratio (%)

(p<0.01). The mean UEDR and TBDR values were higher in construction workers than in other blue-collar workers (textile, mechanic/repair and others), and the difference was statistically significant (p<0.05).

80

60

40

20

R2 Linear = 0.956

0 0

200 400 600 800 Modified Hand Injury Severity Score

1000

Figure 1. Relationship between Modified Hand Injury Severity Score and upper extremity disability ratio.

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Çapkın et al. Associations between MHISS and disability ratings/return to work

showed a correlation coefficient of 0.981 between the MHISS and time to return to work (Fig. 3); this was statistically significant (p<0.001). We found highly significant relationships between the UEDR and time to return to work, as well as the TBDR and time to return to work. The Spearman rank-order method showed a correlation coefficient of 0.908 between the UEDR and time to return to work; this was statistically significant (p<0.001). The Spearman rank-order method showed a correlation coefficient of 0.9 between the TBDR and time to return to work; this was statistically significant (p<0.001). There were no significant relationships between age and the following variables: MHISS, UEDR, TBDR and time to return to work.

60

Total body disability ratio (%)

50

40

30

20

10 R2 Linear = 0.955

0 0

200

400

600

800

1000

Modified Hand Injury Severity Score

Figure 2. Relationship between Modified Hand Injury Severity Score and total body disability ratio.

400

Return to work (days)

300

200

100

R2 Linear = 0.763

0 0

100

200

300

400

500

Modified Hand Injury Severity Score

Figure 3. Relationship between Modified Hand Injury Severity Score and time to return to work.

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DISCUSSION Scoring systems have been used in trauma surgery for more than 40 years.[16] Campbell and Kay specifically designed the HISS system for hand injuries distal to the carpal bones.[3] The MHISS, devised by Urso-Baiarda et al.,[4] is a similar scoring system which includes a wrist and forearm assessment. In the original, prospective study by Urso-Baiarda et al.,[4] a postal questionnaire or semi-structured telephone interview was used; the mean MHISS of the responders (n=84) was 74 (range: 2–712). Sixteen responders (19%) who did not return to their previous employment exhibited a mean MHISS of 151.5. According to Urso-Baiarda et al.,[4] MHISS was the only predictor of return to work among the factors examined; responders with more severe injuries were less likely to return to work. For example, only 60% of those with major hand injuries (as defined by the MHISS) returned to work. In the present study of 94 patients, the mean MHISS was 125.23 (range: 5–880). Seven patients (7.4%) did not return to their previous employment because they had a mean MHISS of 738 (range: 420–880). Notably, 72% of the patients with major injuries, as defined by the MHISS, returned to work. In the present study, the mean injury score was much higher than that reported by Urso-Baiarda et al.,[4] which may be because there were more patients with major injuries in our study than in the prior study. Moreover, patients with different types of injuries might have been assessed in the two studies. Several studies have revealed a positive correlation between the severity of the injury and the length of time to return to work.[2,3,8,14,17,18] Similarly, we found a statistically significant correlation between the MHISS and time to return to work. However, many variables besides the injury itself may influence the time to return to work; these include physical, psychosocial, demographic and employment factors.[8,18–21] Some researchers reported that the time to return to work could be influenced by age and sex.[22] However, in our study, no significant relationship was found between age and the following variables: MHISS, UEDR, TBDR and time to return to work. Trybus et al.[23] have declared that the economic consequences of serious hand injuries are considerable, and approximately 5% of the afflicted have to change their occupation, whereas approximately 5% have to retire. Furthermore, they have reported a clear connection between permanent functional restriction and return to employment.[23] In another study comprising 79 patients aiming direct and indirect costs and factors influencing these costs in patients presenting following traumatic hand injuries, the average time to return to work was 114.7 days. In the same study, while 71% of the patients returned to their previous job, 29% of them had to leave or change their job.[24] In our study, the average time to return to work was 138.7 days, and 86.2% of the patients returned to their previous jobs, whereas 13.8% of the patients had to leave or change their job. Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Çapkın et al. Associations between MHISS and disability ratings/return to work

The literature has a minimal emphasis on the correlation between disability rating and time to return to work. Notably, a disability rating may indicate injured patients’ limitations and permanent abilities; thus, it is a key factor in the return to full employment. Several studies have reported that the initial anatomical severity of a hand injury could influence final hand function as well as disability after maximal recovery.[5–7,19] Mink van der Molen et al.[2] proposed using HISS as a guide to predict outcomes, subsequent impairment and disability. They evaluated correlations between the HISS and measures of impairment and disability six months after a hand injury, as measured using the AMA guidelines.[25] The mean HISS score was 64; the mean AMA impairment for the hand was 17%, for the upper extremity was 25% and for the total body was 15%. Notably, those investigators reported a statistically significant positive correlation between HISS and residual impairment.[2] To our knowledge, this study is the first investigation in Turkey on the relationship between initial anatomical severity of hand, wrist and forearm injuries, as measured by the MHISS, and the disability rating, as evaluated by the ‘Regulation on Disability Criteria, Classification and Health Board Reports to be Given to Disabled People’. This regulation comprises the system currently used in Turkey to measure disability after musculoskeletal injuries and comprises a detailed, reproducible system. We found statistically significant correlations between MHISS and UEDR, TBDR and time to return to work and UEDR, TBDR. Notably, higher MHISS scores were associated with higher disability ratings, as well as less favourable functional results. In addition, the length of time to return to work increased with higher disability ratings. A few studies in Turkey showed that the most common cause of hand injuries was occupational accidents; these injuries primarily occurred in men. In our study, the male-to-female ratio was approximately 3:1; according to the MHISS grade, minor injuries were more common in women, while major injuries were more common in men. This is likely a result of the increased presence of men in industrial work.[26,27] Another study by Sozbilen et al.[12] assessed the characteristics of hand and forearm injuries caused by angle grinders and determined risk factors for this type of injury; the investigators found that the mean overall MHISS score was 74 (2–330), and that angle grinder injuries were often severe, difficult to treat and caused a high rate of resulting disability. Another study by Çakır et al.[28] investigated the relationships between injury severity and the following factors: return to work, impairment, activity and participation levels among patients who had experienced hand and forearm injuries. The investigators found that return to work, return to activity and participation were delayed with increasing MHISS. In our study, the mean MHISS was higher than in previous studies, possibly because we included combined severe crush Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

type injuries, including the hand, wrist and forearm in seven patients in our study. Thus, more complex injuries were associated with increased MHISS. Indeed, the score was quite high in these patients (mean MHISS 738, range: 420–880), so the mean overall MHISS was higher. Previous studies have reported that work accidents result in a longer time to return to work than those occurring elsewhere. The authors suggested that these results could be because work accidents predominantly occur in workers who use hand tools (e.g., carpenters, mechanics, fitters), warranting the need for advanced manual skills for these individuals to continue to their job.[1,5,10,24,29] More than half of the patients (52.1%) included in our study had work accident injuries and their pre-injury jobs (e.g., construction workers, textile workers, mechanic/repair workers) required high-level hand skills. Patients with bilateral injuries or injuries to the other parts of the body were excluded from the study because this would negate (bias) the time to return to work. Furthermore, the claim of the workers’ compensation and litigations may extend the time to return to work.[24,29–31] In our study, seven patients who did not return to work had the right to claim disability benefits according to the Social Insurances and General Health Insurance Law in Turkey. Possibly, these patients experienced benefits from not resuming their work. Injuries to the hand and wrist account for approximately 20% of the visits to emergency departments.[33–35] Although these injuries vary according to the developmental characteristics of the countries and/or regions and the severity of the injuries, they occur mostly after work accidents, and young active men are affected.[13,23,35–37] In our study, young adult men were most commonly affected. This finding is consistent with the literature. Occupational injuries mostly occurred in the construction sector in the studies by Celik et al.[37] and Garg et al.,[38] with rates of 28.7% and 30%, respectively. Ozkan et al.[39] reported that the majority of the victims of occupational accidents worked in the manufacturing and construction sectors (60% and 24%, respectively). Bursa is one of the outstanding industrialized cities of Turkey, particularly in the textile, automotive and construction sectors. In our study, 52.1% of the patients were injured due to occupational accidents, and the most common injuries occurred among textile workers (18.1%), mechanic/repair workers (13.8%) and construction workers (10.6%). These sectoral variations are probably due to regional differences. Our study had several limitations. First, the method involved a retrospective design. Second, only one surgeon graded all MHISS scores and disability ratings, so the study exhibits internal inconsistency. Further research is needed on the reliability and validity of disability rating measurements and of the MHISS. Third, there was no standard postoperative regular rehabilitation programme for patients included in this study. Fourth, workers’ compensation cases were not well 459


Çapkın et al. Associations between MHISS and disability ratings/return to work

documented in our study. There may be a difference between recovery time and return to work after hand injury.[5,13] This difference may be because the patient working in a job that does not require dexterity returns to work early without complete recovery, whereas the patient working in a job that requires dexterity returns to work only after recovery occurs. Another disadvantage of our study was that factors, such as recovery time, length of hospital stay and the number of re-operations required for recovery, were not included in this study because the main objective of our study was to investigate the relationship between post-injury severity score and return to work.

Conclusion Our results associated higher MHISS scores with increased disability ratings and longer time to return to work. Notably, as the initial injury severity increased, greater disability remained and the time to return to work increased. Predicting prognosis by determining the injury severity in the initial evaluation of patients may be important in predicting a patient’s future permanent disability level; this can contribute to maintaining patient expectations at a reasonable level, thereby aiding in psychosocial support. This can also be important for employers who need to plan for the patient’s return to work, as well as to identify patients who cannot return to their prior roles. Further studies with a larger sample are recommended to verify the validity of the findings and to complete missing aspects. Ethics Committee Approval: This retrospective study was approved by the Clinical Research Ethics Committee of the Bursa Uludağ University Faculty of Medicine (Approval no: 2019-2/9). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: S.Ç., A.C., T.K.; Design: S.Ç., K.Y., E.E., T.K.; Supervision: S.Ç., A.C., T.K.; Fundings: S.Ç., A.C., K.Y., E.E., T.K.; Materials: S.Ç., A.C., T.K.; Data: S.Ç., A.C., K.Y., E.E.; Analysis: S.Ç., A.C., K.Y., E.E., T.K.; Literature search: S.Ç., A.C., K.Y., E.E.; Writing: S.Ç., A.C., K.Y., E.E.; Critical revision: S.Ç., AC, T.K. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

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Çapkın et al. Associations between MHISS and disability ratings/return to work 2013;38:673–9. 25. Doege TC. AMA Guides to the Evaluation of Permanent Impairment. 4th edition. Chicago, IL: American Medical Association; 1993. 26. Ozçelik B, Ertürer E, Mersa B, Purisa H, Sezer I, Tunçer S, et al. An alternative classification of occupational hand injuries based on etiologic mechanisms: the ECOHI classification. Ulus Travma Acil Cerrahi Derg 2012;18:49−54. 27. Davas Aksan A, Durusoy R, Ada S, Kayalar M, Aksu F, Bal E. Epidemiology of injuries treated at a hand and microsurgery hospital. Acta Orthop Traumatol Turc 2010;44:352–60. 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. Johns AM. Time off work after hand injury. Injury 1981;12:417–24. 30. Woodyard JE. Injury, compensation claims and prognosis: part I. J Soc Occup Med 1980;30:2–5. 31. Woodyard JE. Injury, compensation claims and prognosis: Part II. J Soc Occup Med 1980;30:57–60. 32. de Putter CE, Selles RW, Polinder S, Panneman MJ, Hovius SE, van

Beeck EF. Economic impact of hand and wrist injuries: health-care costs and productivity costs in a population-based study. J Bone Joint Surg Am 2012;94:e56. 33. Larsen CF, Mulder S, Johansen AM, Stam C. The epidemiology of hand injuries in The Netherlands and Denmark. Eur J Epidemiol 2004;19:323–7. 34. Angermann P, Lohmann M. Injuries to the hand and wrist. A study of 50,272 injuries. J Hand Surg Br 1993;18:642–4. 35. Sorock GS, Lombardi DA, Hauser RB, Eisen EA, Herrick RF, Mittleman MA. Acute traumatic occupational hand injuries: type, location, and severity. J Occup Environ Med 2002;44:345–51. 36. Unlü RE, Abacı Ünlü E, Orbay H, Sensöz O, Ortak T. Crush injuries of the hand. Ulus Travma Acil Cerrahi Derg 2005;11:324–8. 37. Celik K, Yilmaz F, Kavalci C, Ozlem M, Demir A, Durdu T, et al. Occupational injury patterns of Turkey. World J Emerg Surg 2013;8:57. 38. Garg R, Cheung JP, Fung BK, Ip WY. Epidemiology of occupational hand injury in Hong Kong. Hong Kong Med J 2012;18:131–6. 39. Ozkan S, Kiliç S, Durukan P, Akdur O, Vardar A, Geyik S, et al. Occupational injuries admitted to the Emergency Department. Ulus Travma Acil Cerrahi Derg 2010;16:241−7.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut el, el bileği ya da ön kol yaralanmalarında yaralanmanın ciddiyeti ile özürlülük oranları ve işe geri dönüş zamanı arasındaki ilişki Dr. Sercan Çapkın, Dr. Ali Cavit, Dr. Kutay Yılmaz, Dr. Eralp Erdoğan, Dr. Tufan Kaleli Uludağ Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, El Cerrahisi Bilim Dalı, Bursa

AMAÇ: Modifiye El Yaralanması Ciddiyet Skoru (MEYCS) ile değerlendirilen el, el bileği ve ön kol yaralanmalarının başlangıçtaki anatomik şiddeti ile yaralanma sonrası özürlülük oranları ve işe geri dönüş zamanı arasındaki ilişkiyi araştırmaktır. GEREÇ VE YÖNTEM: Çalışmaya akut el, el bileği ve önkol yaralanması nedeniyle ameliyat edilen 94 hasta alındı. Yaralanmanın şiddeti MEYCS ile belirlendi. Yaralanmadan 6 ay sonra hastaların özürlülük oranları ‘Özürlülük Ölçütü, Sınıflandırması ve Özürlülere Verilecek Sağlık Kurulu Raporları Hakkında Yönetmelik’e göre hesaplandı. İşe geri dönüş süresi, yaralanma ile hastanın işe geri dönüşü arasındaki sürenin (gün) uzunluğu olarak tanımlandı. MEYCS ile özürlülük oranları ve işe geri dönüş zamanı arasındaki ilişki Sperman korelasyon analizi ile araştırıldı. BULGULAR: Ortalama MEYCS; 125.23 (5–880), üst ekstremite özürlülük oranı (ÜEÖO);17.64±22.6 (dağılım: 0–94) ve total vücut özürlülük oranı (TVÖO); 10.57±13.45 (dağılım: 0–56) olarak bulundu. Çalışmaya dahil edilen 87 (92.6%) hasta eski işine geri döndü. Ortalama işe geri dönüş zamanı; 138.69 (dağılım: 35–365 gün) olarak bulundu. MEYCS ile ÜEÖO ve TVÖO arasında, işe geri dönüş zamanı ile ÜEÖO ve TVÖO arasında istatiksel olarak anlamlı bir korelasyon bulundu (p<0.001). TARTIŞMA: Sonuç olarak, yaralanmanın başlangıçtaki şiddeti arttıkça hastaların özürlülük oranları ve işe geri dönüş zamanları artmaktadır. Hastaların ilk değerlendirmesinde yaralanmanın ciddiyetini saptayarak prognoz hakkında ön görüye sahip olmak hastaların gelecekteki kalıcı sakatlık seviyesini tahmin etmede ve böylelikle hasta beklentilerinin makul düzeyde tutulması sağlanarak psikososyal destek açısından önemli olabilir. Anahtar sözcükler: İşe geri dönüş zamanı; MEYCS; özürlülük oranı; yaralanma şiddeti. Ulus Travma Acil Cerrahi Derg 2020;26(3):453-461

doi: 10.14744/tjtes.2019.40524

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ORIGIN A L A R T IC L E

Compliance with PECARN head injury decision rules in children under two years old Aydın Gerilmez, M.D.,

Arif Tarkan Çalışaneller, M.D.

Department of Neurosurgery, University of Health Sciences, Haydarpaşa Numune Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: One of the most common complaints about presentation at the Emergency Department (ED) in childhood is minor head trauma. In recent years, clinical decision rules (CDRs) have been published to assist in determining the need for performing computed tomography (CT) in these patients. The present study aims to investigate the compliance with Pediatric Emergency Care Applied Research Network (PECARN) rules in the decisions for CT examination in children aged below two years old with minor head trauma in our center. METHODS: This retrospective, single-center study was conducted on a patient group aged below two years old, who presented at the ED within 24 hours of a trauma incident and were diagnosed as mild head trauma Glasgow Coma Scale score 14 and 15). RESULTS: A total of 262 patients were included in this study. Of these patients, 214 (81.7%) received CT examination, and 48 (18.3%) patients did not receive any CT examination. None of these 48 patients showed clinically important traumatic brain injury (ci TBI). Among 214 patients who received CT examination, 89 (34%) patients met the PECARN rules criteria and 125 (47.7%) patients did not meet PECARN rules criteria. None of the patients who received CT examination and did not meet the PECARN rules criteria showed ci TBI. Among 89 patients who recieved a CT examination and also met the PECARN rules criteria, only 4 (1.5%) patients showed ci TBI. According to these results, the rate of compliance with PECARN rules in our institution ED was 52.3%. CONCLUSION: In this study, which was conducted by including all the predictor values of the PECARN guidelines, the rate of compliance with PECARN rules was determined to be very low. Using these rules directly or with modification could establish a starting point for clinicians to reduce the rates of unnecessary CT scans. However, the effects of the clinician’s experience, parental expectations, medicolegal constraints and economic factors on the decision making process should not be forgotten. Keywords: Children; computed tomography; head injury; PECARN.

INTRODUCTION One of the most common reasons for presentation at the Emergency Department (ED) in childhood is head trauma.[1] The annual incidence is estimated as 1850/100.000 (0–4 years old),[2] and the majority of cases (80–90%) are minor trauma. [3,4] While no intracranial pathology develops in most of these patients, clinically important traumatic brain injury (ciTBI) may develop in a small portion despite the head trauma being a minor. Computed tomography (CT) is the standard diagnostic test in the definition of these pathologies. However, the results of studies related to radiation-induced cancer

have raised concerns about the application of CT, especially in young patients.[5,6] In addition, there are studies that have related cognitive disorders in adult life to exposure of the infant’s brain to ionising radiation.[7] Another negative aspect is the need for sedation during scanning because of agitation in some children.[8,9] Because of these reasons, some clinical decision rules (CDRs) have been published in recent years to assist in the determination of the need for CT in children presented with minor head trauma. By determining the patient group at high risk in respect to intracranial injury, CDRs aim to be

Cite this article as: Gerilmez A, Çalışaneller AT. Compliance with PECARN head injury decision rules in children under two years old. Ulus Travma Acil Cerrahi Derg 2020;26:462-468. Address for correspondence: Aydın Gerilmez, M.D. Sağlık Bilimleri Üniversitesi, Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, Beyin ve Sinir Cerrahisi Kliniği, İstanbul, Turkey Tel: +90 216 - 542 32 32 E-mail: aydingerilmez@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):462-468 DOI: 10.14744/tjtes.2019.36902 Submitted: 23.05.2019 Accepted: 25.10.2019 Online: 13.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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of assistance to clinicians in reducing the need for CT scanning.[10,11] One of the widely-used guidelines is the Pediatric Emergency Care Applied Research Network (PECARN) rules. PECARN is a reliable guideline in the determination of the high-risk patient group with 100% sensitivity, 53.8% specificity, 2% positive predictive value (PPV) and 100% negative predictive value (NPV).[1] However, despite all these guidelines, reports that have determined an increase in CT scanning rates in children with head trauma have been published.[12,13]

The inclusion and exclusion criteria of the PECARN study for children aged <2 years with minor head trauma, the rule-specific predictor variables and outcomes are shown in Table 1. Similar to the PECARN study, ciTBI was used as the outcome in this study. ciTBI is defined in Table 1. Table 1. Inclusion and exclusion criteria, predictor variables and outcome measures of PECARN clinical decision rules PECARN <2 years old Inclusion criteria

Age <2 years, presenting within 24 h of

head injury

Exclusion criteria

Trivial mechanism of injury, defined by

ground-level fall or walking or running

into stationary objects and no signs or

This retrospective, single-centre study was conducted on a paediatric population aged <2 years old who presented at the ED units of our hospital because of mild head trauma. Data were collected by examining the medical records for demographic characteristics, trauma history, physical and neurological examination findings and the diagnostic tests applied to the patients. The patients included in this study who presented at ED within 24 hours of the trauma incident and were diagnosed with mild head trauma (GCS 14–15). For the follow-up of patients who had not been applied with neuroimaging, the family was contacted by telephone.

symptoms of head trauma other than

scalp abrasions and lacerations

Penetrating trauma

Known brain tumours

Pre-existing neurological disorder

Neuroimaging at an outside hospital

before transfer

Patient with a ventricular shunt

Patient with a bleeding disorder

GCS score <14

In a one-month duration, a total of 342 patients were identified who were aged <2 years and presented at ED with complaints of minor head trauma. Forty-eight patients were excluded from this study given that the medical records were deemed insufficient for evaluation. Of the remaining 294 patients, 10 were excluded as they presented after 24 hours or presented again for the same reason, and a further 22 were excluded as they could not be contacted for follow-up. Finally, an evaluation was made in 262 patients. The study profile is shown in Figure 1.

Predictor variables (all)

The present study aims to investigate the compliance of CT decisions to PECARN rules in children aged <2 years who presented at ED with minor head trauma in our institution.

MATERIALS AND METHODS

342 patients presenting to ED with minor head injury 48 cases for assessment

Mechanism of injury

Severe mechanism of injury (MVC with

patient ejection, death of another

passenger, or rollover; pedestrian or

bicyclist without helmet struck by

motorised vehicle; falls >0·9 m; or head

struck by high-impact object)

History

Loss of consciousness for ≥5 s

Not acting normally per parent report

Examination

GCS score <15

Other signs of altered mental status

(agitation, somnolence, repetitive

questioning, slow response to verbal

communication) 294 cases assessed for eligibility 10 cases excluded-2 repeat presentation for same trauma -8 cases presenting after 24h 284 cases eligible 22 cases lost to fololw-up 262 evaluable for analysis

Figure 1. Study profile.

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Palpable or unclear skull fracture

Occipital, parietal, or temporal scalp

haematoma Outcome

ciTBI, defined as death from TBI,

neurosurgical intervention for TBI,

intubation of more than 24 h for TBI or

hospital admission of two nights or

more for TBI, associated with TBI on CT

GCS: Glasgow Coma Scale; ciTBI: Clinically important traumatic brain injury.

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Table 2. Patient characteristic

Table 3. Presence of the PECARN predictor variables

n

%

Demographic characteristics Boy

158 60.3

Girl

104 39.7

Clinician-assigned GCS score 14

3

15

1.1

259 98.9

Mechanism of injury Fall

230 87.8

Head hit by high impact object

28

10.7

Motor vehicle incident

3

1.1

Suspected non-accidental injury

1

0.49

214

81.6

4

1.5

PECARN in children aged <2 years Predictor variables

n

%

GCS score <15

3

1.1

Other sign of altered mental status

18

6.9

Scalp hematoma (oksipital, temporal or parietal)

31

11.8

History of loss of consciousness ≼5 s

4

1.5

Acting abnormal per parent

38

14.5

Palpable or unclear skull fracture

0

Severe mechanism of injury

52

19.8

PECARN: Pediatric Emergency Care Applied Research Network; GCS: Glasgow Coma Scale.

Outcomes

Cranial CT

ci TBI

Neurosurgery

0

0

Death

0

0

GCS: Glasgow Coma Scale; CT: Computed tomography; ciTBI: Clinically important traumatic brain injury.

The compliance with the PECARN rules in the decision of CT examination for the patients was examined.

RESULTS Two hundred sixty-two patients were included in this study. Gender distribution was 158 (60.3%) males and 104 (39.7%) females. The GCS score on the presentation at ED was 14 in three (1.1%) patients and 15 in 259 (98.9%). The head trauma mechanism was a fall in 230 (87.8%) cases, the head struck by a high-impact object in 28 (10.7%), motor vehicle accident-related injury (MVI) in three (1.1%) cases and suspected non-accidental injury (NAI) in one (0.49%) case.

Of the 262 patients, CT was applied to the decision of the clinician in 214 (81.6%) cases, ciTBI developed in four (1.5%) cases, no neurosurgical intervention was applied in any case, and no mortality developed in any patient (Table 2). The most frequently determined PECARN predictor variable was severe mechanism of injury in 52 (19.8%) patients, GCS score was determined as <15 in 3 (1.1%) patients, other signs of altered mental status in 18 (6.9%), scalp hematoma (occipital, temporal or parietal) in 31 (11.8%), history of loss of consciousness of ≼5 sec in four (1.5%) and behaving abnormally according to the parent in 38 (14.5%) (Table 3). A total of 262 patients were included in this study. Of these patients, 214 (81.7%) received CT examination, and 48 (18.3%) patients did not receive any CT examination. None of these 48 patients showed ci TBI. Among 214 patients who received CT examination, 89 (34%) patients met the PECARN rules criteria and 125 (47.7%) patients did not meet PECARN rules criteria. None of the patients who received the CT examination and did not meet the PECARN rules criteria show ci TBI. Among 89 patients who received CT ex-

262 cases evaluable for analysis

214 cases with CT outcome

89 cases positive on PECARN criteria

4 cases with ciTBI outcome

85 cases without ciTBI outcome

48 cases without CT outcome

125 cases negative on PECARN criteria

125 cases without ciTBI outcome

48 cases negative on PECARN criteria

48 cases without ciTBI outcome

Figure 2. Outcome analysis.

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Table 4. Clinically important traumatic brain injury outcome PECARN in children aged <2 years (n=262)

n

%

ciTBI

4 1.5

Positive on criteria

89

34

With outcome (n)

4

1.5

Without outcome (n)

85

32.4

173

66

0

0

173

66

Negative on criteria

With outcome (n)

Without outcome (n)

PECARN: Pediatric Emergency Care Applied Research Network; ciTBI: Clinically important traumatic brain injury.

Table 5. CT outcome PECARN in children aged <2 years (n=262)

n

%

CT

214

81.7

Positive on criteria

89

34

With outcome (n)

89

34

Without outcome (n)

0

0

Negative on criteria

173

66

With outcome (n)

125

47.7

Without outcome (n)

48

18.3

PECARN: Pediatric Emergency Care Applied Research Network; CT: Computed tomography.

amination and also met the PECARN rules criteria, only four (1.5%) patients showed ci TBI (Fig. 2). According to these results, the rate of compliance with PECARN rules in our instutition was 52.3% (Table 4, 5).

DISCUSSION CDRs aim to reduce CT scanning as an aid to clinicians in identifying the patient group at high risk of intracranial injury in cases of head trauma. PECARN, Children’s Head injury Algorithm for the prediction of Important Clinical Events (CHALICE) and Canadian Assessment of Tomography for Childhood Head injury (CATCH) are guidelines widely used for this purpose. In this study, which was designed to investigate the compliance with these guidelines of the decision for CT in children with minor head trauma aged <2 years, the first decision to be made was to determine which of these guidelines would be most suitable for clinical use. Therefore, literature was scanned for extensive cohort studies that have analysed the factors affecting this multifactorial decision. The recent, prospective Paediatric Research in Emergency Departments International Collaborative (PREDICT) study with a patient population of 20.137 was used to make this decision.[14] Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

In the PREDICT study, ciTBI was used as the common outcome measurement, as it was in the original PECARN study, to provide a more valid outcome in respect of family, clinician and the healthcare system, comparing the three CDRs of outcome measurements, inclusion and exclusion criteria, which are different.[14] As the primary outcome in the CATCH study is death and neurosurgical intervention, these results are very limited, and it is very risky in respect of overlooking trauma-related morbidity.[14,15] On the other hand, the outcome of the CHALICE study includes CT abnormalities, which may not be clearly related to clinical results.[14,16] The comparative cohort in the PREDICT study was similar to that of our study as it included paediatric patients who presented within 24 hours with a mild injury following trauma. CDRs must have very high sensitivity in the determination of cranial injuries and high NPV in the identification of patients at low risk. Similar to the PECARN original derivation study, in the PREDICT study with an extensive comparative cohort, ciTBI was determined to have high sensitivity in the prediction in both age years (<2 years 100%, >2 years 99.2%). CATCH rules sensitivity was determined as 91.9%, similar to the derivation study. When CHALICE predictive values were used, sensitivity was 92.5%. Both CATCH (70.4%) and CHALICE (78.6%) have higher specificity than PECARN (59.1%).[14] In their study, Bozan et al.[17] compared PECARN and CATCH clinical decision rules in children minor head trauma and reported that the sensitivity of PECARN was 95 (95% Cl 72– 100) and specificity was 53 (95% CI 47–60%), whereas the sensitivity of CATCH was 48 (95% CI 25–71%), and specificity was 83 (95% CI 79–88%). Therefore, they concluded that although both PECARN and CATCH where effective in the clinical decision making for CT scanning, PECARN was more useful for emergency services due to higher sensitivity. In another study, Gokharman et al.[18] studied PECARN rules on the basis of cost and effectiveness. They found that PECARN rules could successfully predict pathology and decrease resource waste and exposure to radiation in pediatric head traumapatients. Even though there is a balance between sensitivity and specificity, it is difficult to accept increased specificity at the cost of reduced sensitivity, as the reduced sensitivity may cause intracranial traumatic lesions that require surgical intervention to be overlooked, thereby resulting in morbidity and mortality. Therefore, for both the patient and clinician, priority is given to high sensitivity.[14] For all these reasons, compliance with the CT decisions according to the PECARN rules was selected in this study. 465


Gerilmez et al. Compliance with PECARN head injury decision rules in children under two years old

In our study, the GCS score on the presentation at ED was determined as 14 in three (1.1%) patients and 15 in 259 (98.9%) patients, while the rates in the PECARN validation study cohort were GCS 14 in 3.2% and GCS 15 in 96.8%.[1] In the PREDICT study, the rate of patients with GCS 14 was 2.9% and GCS 15 was 95.4%.[14] The head trauma mechanism was a fall in 230 (87.8%) cases, the head struck by a high-impact object in 28 (10.7%) cases, MVI in three (1.1%) cases and suspected NAI in one (0.49%) case. The most common mechanism of head trauma was determined as a fall because this patient group was aged <2 years and at the developmental stage of learning to walk. In the PREDICT study of the current study cohort, the mechanisms of injury most determined were fall-related head injury (70.1%), followed by head struck by high-impact object or projectile (6.6%).[14] Of the PECARN predictor variables used in our study to investigate the high-risk group in respect of ciTBI development, the most commonly determined variable was severe mechanism of injury in 52 (19.8%) patients, GCS score was determined as <15 in 3 (1.1%) patients, other signs of altered mental status in 18 (6.9%), scalp hematoma (occipital, temporal or parietal) in 31 (11.8%), history of loss of consciousness of ≥5 sec in four (1.5%) and behaving abnormally according to the parent in 38 (14.5%) patients. In the PREDICT study, the PECARN predictor variables were determined as a severe mechanism of injury (20.5%), scalp hematoma (12.3%), behaving abnormally according to the parent (12.1%), other signs of altered mental status in 18 (6.3%), history of loss of consciousness of ≥5 sec (3%), palpable or unclear skull fracture (2.9%) and GCS score <15 (2.7%), respectively.[14] Of the 89 patients in our study who met the criteria according to the PECARN rules, ciTBI was determined in four patients. In the 173 patients who did not meet the criteria, no ciTBI was determined. In the PREDICT study of children aged <2 years, ciTBI was determined in 42 of 20149 patients who met the criteria, and no ciTBI was reported in the 2957 patients who did not meet the criteria. Sensitivity was reported as 100% (95% CI, 91.6–100.0), specificity as 59.4% (95% CI, 57.5–60.5), PPV as 2.0% (1.5–2.7), and NPV as 100% (99.0–100).[14] In our study, sensitivity, specificity and PPV could not be statistically evaluated as the sample volume was insufficient. However, ciTBI did not develop in any patient that did not meet the criteria was similar to the findings of the PREDICT study. When the PECARN rules were applied to our study population, although CT examination was approved for 89 (34%) patients, it was determined that CT was applied to 214 (81.6%) of the total 262 patients on the decision of the clinician. In the PREDICT study, CT was reported to be performed 10.5% of the patients. However, with the application of CATCH and 466

CHALICE to this comparative cohort, these rates were reported to be 22.0% and 30.2%, respectively, thus would show an increase of 150%–250%. Determination of predicted CT rates is more difficult in cohorts applied with the PECARN guidelines because some of the low-risk patients may need either CT scanning or clinical observation. When all the PECARN predictors were included in the PREDICT of children aged <2 years (n=4011), it was reported that 1872 patients met the criteria. This provided a CT scan rate of 46.7%. In the original PECARN validation study, the CT scan rate was reported as 35.3%.[1] This rate was 30.2% in the CATCH study (performance of the four high-risk factors relation to need for neurological intervention)[15] and 14.1% in the CHALICE study (prediction of important clinical events rule).[16] In a retrospective, multicentre study of children aged <2 years with a mild head injury, Velasco et al.[19] reported that the rate of compliance to PECARN guidelines was >50% in only three of four hospitals and the most successful compliance rate was 70%. In a study by Tama et al.,[20] no difference was seen between doctors of different specialties in respect of compliance to PECARN criteria in paediatric patients with acute head trauma and general compliance was reported as 93%. Kobe et al.[21] reported that the rate of CT scans decreased from 56% to 33% after the use of PECARN in pediatric acute head trauma cases, no ciTBI was overlooked and the discharge rate increased from 58% to 81%. Studies that have evaluated the effects of the application of PECARN guidelines have shown an effective reduction in CT rates in centers with high CT use and no increase in centers with low CT rates.[22] In our study, when the PECARN rules were applied, the CT rate was 34%, which is similar to the original PECARN study. However, the actual rate of CT scans taken on the decision of the clinician was 81.7%. CT scanning was applied to all 89 patients for whom it was deemed necessary according to the PECARN rules. However, additional 125 patients who did not require CT, according to PECARN, also received CT examination. CT scan was not performed in only 48 patients in our study group. Thus, in a total of 137 patients (89 patients with CT outcome and 48 patients without CT outcome), the decision was made in conformity with the PECARN rules. When all the predictors were included, including in the whole population those referred to as low-risk in the PECARN guideline, the rate of compliance to the PECARN rules was 52.3%.

Conclusion In this study, which was conducted by including all the predicUlus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Gerilmez et al. Compliance with PECARN head injury decision rules in children under two years old

tor values of the PECARN guidelines, the rate of compliance with PECARN rules was determined to be very low. Using these rules directly or with modification could establish a starting point for clinicians to reduce the rates of unnecessary CT scans. However, the effects of the clinician’s experience, parental expectations, medicolegal constraints and economic factors on decision making process should not be forgotten. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.G., A.T.Ç.; Design: A.G., A.T.Ç.; Supervision: A.G., A.T.Ç.; Fundings: A.G., A.T.Ç.; Materials: A.G., A.T.Ç.; Data: A.G., A.T.Ç.; Analysis: A.G., A.T.Ç.; Literature search: A.G., A.T.Ç.; Writing: A.G., A.T.Ç.; Critical revision: A.G., A.T.Ç. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Kuppermann N, Holmes JF, Dayan PS, Hoyle JD Jr, Atabaki SM, Holubkov R, et al; Pediatric Emergency Care Applied Research Network (PECARN). Identification of children at very low risk of clinicallyimportant brain injuries after head trauma: a prospective cohort study. Lancet 2009;374:1160−70. 2. McKinlay A, Grace RC, Horwood LJ, Fergusson DM, Ridder EM, MacFarlane MR. Prevalence of traumatic brain injury among children, adolescents and young adults: prospective evidence from a birth cohort. Brain Inj 2008;22:175–81. 3. Ayr LK, Yeates KO, Taylor HG, Browne M. Dimensions of postconcussive symptoms in children with mild traumatic brain injuries. J Int Neuropsychol Soc 2009;15:19–30. 4. Crowe LM, Anderson V, Catroppa C, Babl FE. Head injuries related to sports and recreation activities in school-age children and adolescents: data from a referral centre in Victoria, Australia. Emerg Med Australas 2010;22:56–61. 5. Faulkner K, Moores BM. Radiation dose and somatic risk from computed tomography. Acta Radiol 1987;28:483–8. 6. Brenner DJ, Hall EJ. Computed tomography--an increasing source of radiation exposure. N Engl J Med 2007;357:2277–84. 7. Hall P, Adami HO, Trichopoulos D, Pedersen NL, Lagiou P, Ekbom A, et al. Effect of low doses of ionising radiation in infancy on cognitive function in adulthood: Swedish population based cohort study. BMJ 2004;328:19. 8. Vade A, Sukhani R, Dolenga M, Habisohn-Schuck C. Chloral hydrate sedation of children undergoing CT and MR imaging: safety as judged by American Academy of Pediatrics guidelines. AJR Am J Roentgenol 1995;165:905–9. 9. Conners GP, Sacks WK, Leahey NF. Variations in sedating uncooperative, stable children for post-traumatic head CT. Pediatr Emerg Care 1999;15:241–4.

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10. Lyttle MD, Crowe L, Oakley E, Dunning J, Babl FE. Comparing CATCH, CHALICE and PECARN clinical decision rules for paediatric head injuries. Emerg Med J 2012;29:785–94. 11. Pickering A, Harnan S, Fitzgerald P, Pandor A, Goodacre S. Clinical decision rules for children with minor head injury: a systematic review. Arch Dis Child 2011;96:414–21. 12. Stanley RM, Hoyle JD Jr, Dayan PS, Atabaki S, Lee L, Lillis K, et al; Pediatric Emergency Care Applied Research Network (PECARN). Emergency department practice variation in computed tomography use for children with minor blunt head trauma. J Pediatr 2014;165:1201−6. e2. 13. Klassen TP, Reed MH, Stiell IG, Nijssen-Jordan C, Tenenbein M, Joubert G, et al. Variation in utilization of computed tomography scanning for the investigation of minor head trauma in children: a Canadian experience. Acad Emerg Med 2000;7:739−44. 14. Babl FE, Borland ML, Phillips N, Kochar A, Dalton S, McCaskill M, et al; Paediatric Research in Emergency Departments International Collaborative (PREDICT). Accuracy of PECARN, CATCH, and CHALICE head injury decision rules in children: a prospective cohort study. Lancet 2017;389:2393−402. 15. Osmond MH, Klassen TP, Wells GA, Correll R, Jarvis A, Joubert G, et al; Pediatric Emergency Research Canada (PERC) Head Injury Study Group. CATCH: a clinical decision rule for the use of computed tomography in children with minor head injury. CMAJ 2010;182:341−8. 16. Dunning J, Daly JP, Lomas JP, Lecky F, Batchelor J, Mackway-Jones K; Children’s head injury algorithm for the prediction of important clinical events study group. Derivation of the children’s head injury algorithm for the prediction of important clinical events decision rule for head injury in children. Arch Dis Child 2006;91:885−91. 17. Bozan Ö, Aksel G, Kahraman HA, Giritli Ö, Eroğlu SE. Comparison of PECARN and CATCH clinical decision rules in children with minor blunt head trauma. Eur J Trauma Emerg Surg 2019;45:849–55. 18. Gökharman FD, Aydın S, Fatihoğlu E, Koşar PN. Pediatric Emergency Care Applied Research Network head injuryprediction rules: on the basis of cost and effectiveness. Turk J Med Sci 2017;47:1770−7. 19. Velasco R, Arribas M, Valencia C, Zamora N, Fernández SM, Lobeiras A, et al. Adecuación del manejo diagnóstico del traumatismo craneoencefálico leve en menores de 24 meses a las guías de práctica clínica de PECARN y AEP [Compliance with the PECARN and AEP guidelines in diagnostic approach of mild head trauma in patients younger than 24 months old]. An Pediatr (Barc) 2015;83:166−72. 20. Tama M, Andharia N, Bufano C, Greenstein J, Khodorkovsky B. Does Specialty Training and Practice Setting Affect Adherence to the Pediatric Emergency Care Applied Research Network Criteria for Pediatric Head Trauma? Pediatr Emerg Care. 2017 Nov 27. doi: 10.1097/ PEC.0000000000001364. [Epub ahead of print]. 21. Kobe IO, Qureshi MM, Hassan S, Oluoch-Olunya DL. The impact of the introduction of PECARN head CT rules on the utilisation of head CT scans in a private tertiary hospital in Sub-Saharan Africa. Childs Nerv Syst 2017;33:2147–52. 22. Bressan S, Romanato S, Mion T, Zanconato S, Da Dalt L. Implementation of adapted PECARN decision rule for children with minor head injury in the pediatric emergency department. Acad Emerg Med 2012;19:801–7.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

İki yaşından küçük çocuklarda PECARN kafa kravması klinik karar kurallarına uyum Dr. Aydın Gerilmez, Dr. Arif Tarkan Çalışaneller Sağlık Bilimleri Üniversitesi, Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, Beyin ve Sinir Cerrahisi Kliniği, İstanbul

AMAÇ: Çocukluk çağında acil servise başvuruların yaygın nedenlerinden biri çoğunluğu minör olan kafa travmalarıdır. Bu hastalarda BT (bilgisayarlı tomografi) çekim ihtiyacının belirlenmesine yardımcı olması amacıyla son birkaç yılda bazı klinik karar kuralları yayınlanmıştır. Bu çalışmada iki yaşından küçük minör kafa travmalı çocuklarda BT çekim kararlarında PECARN (Pediatric Emergency Care Applied Research Network) kurallarına uyum araştırıldı. GEREÇ VE YÖNTEM: Bu geriye dönük, tek merkezli çalışma iki yaşından küçük, travma oluşumunu takip eden ilk 24 saat içinde acil servise ilk başvurusunu yapan ve başvuru Glaskow Koma Skala skorları 14 ve 15 olan hafif kafa travmalı hasta grubunda yürütüldü. BULGULAR: Çalışmaya toplam 262 hasta dahil edildi. Bu hastaların 214’üne (%81.7) BT incelemesi yapıldığı, 48’ine (%18.3) yapılmadığı saptandı. BT taraması yapılmayan 48 hastanın hiçbirinde klinik olarak önemli travmatik beyin hasarı gelişmediği belirlendi. BT incelemesi yapılan 214 hastadan 89’unda (%34) BT çekim kararı verilirken PECARN kurallarına uyulduğu, 125 (%47.7) hastada bu kurallarına uyulmadığı saptandı. PECARN kriterlerini karşılamayan ve BT incelemesi yapılan hastaların hiçbirinde klinik olarak önemli travmatik beyin hasarı gelişmediği, PECARN kriterlerini karşılayan 89 hastanın sadece dördünde (%1.5) klinik olarak önemli travmatik beyin hasarı geliştiği saptandı. Bu sonuçlara göre, kurumumuzda PECARN kurallarına uyum oranı %52.3 idi. TARTIŞMA: PECARN kılavuzunun tüm belirleyici kriterleri dahil edilerek yürütülen çalışmamızda PECARN kurallarına uyum oranının düşük olduğu saptanmıştır. Gereksiz BT çekim oranlarının düşürülmesi için klinisyenlerin bu kuralları direkt veya modifiye ederek kullanması iyi bir başlangıç noktası oluşturabilir. Fakat klinisyen deneyimi, ebeveyn beklentisi, medikolegal çekinceler ve ekonomik faktörlerin bu karar üzerindeki etkisi unutulmamalıdır. Anahtar sözcükler: Bilgisayarlı tomografi; çocuk; kafa travması; PECARN. Ulus Travma Acil Cerrahi Derg 2020;26(3):462-468

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doi: 10.14744/tjtes.2019.36902

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CAS E SERI ES

The role of VATS in the diagnosis and treatment of diaphragmatic injuries after penetrating thoracic traumas Fazlı Yanık, M.D.,

Yekta Altemur Karamustafaoğlu, M.D.,

Yener Yörük, M.D.

Department of Thoracic Surgery, Trakya University Faculty of Medicine, Edirne-Turkey

ABSTRACT BACKGROUND: Diaphragmatic injuries, which can be seen after penetrating thoracic traumas, have some difficulties in diagnosis. Undiagnosed small diaphragmatic lacerations may lead to serious health problems. This study aims to evaluate the role of VATS (Video Assisted Thoracoscopic Surgery) in the diagnosis and treatment of diaphragmatic injuries after penetrating thoracic traumas. METHODS: Among 268 penetrating thoracic trauma patients, we retrospectively evaluated a total of 22 patients performed VATS due to suspected diaphragmatic injury in our department between June 2008 and June 2018. RESULTS: Twenty (91%) patients were male, and two (9%) patients were female with a mean age of 28.01±6.4 (18–42) years. In 11 (50%) patients, VATS was performed on the right side and the others on the left side according to the penetrating area of trauma. In 10 (45%) patients, diaphragmatic laceration was detected and was repaired. In six cases (27%) in which diaphragmatic laceration detected with VATS, preoperative traumatic pathologies were detected radiologically. The missed injury rate was 18%. VATS had a specificity, sensitivity, positive predictive value and negative predictive value of 75%, 71.5%, 60% and 83.3%, respectively. There was no significant statistical difference between types of penetrating trauma, ages and gender of cases (p>0.05). No complication was detected during the mean follow up period of 36.2±9.3 (range 9–62) months. CONCLUSION: Our opinion is that VATS is important and feasible in hemodynamically stable patients with suspected isolated diaphragmatic laceration after penetrating thoracic trauma that cannot be determined by radiologically. Keywords: Diaphragma; penetratin; thoracoscopy; trauma.

INTRODUCTION The most common cause of death in the first four decades of life is trauma. Approximately 20–25% of these deaths are due to thoracic trauma. Thoracic injuries are responsible for mortality in 50% of trauma deaths. Many deaths occurring within minutes or a few hours of injury can be prevented with rapid diagnosis and appropriate treatment of trauma.[1,2] We can basically divide the thoracic trauma as blunt, penetrating, blast and inhalation injury. Esophagus, trachea, heart, diaphragm, large vessels, lung, bone and soft tissue structures of the thoracic cavity may be injured. Physiological results of thoracic trauma are hypoxia, hypercarbia, hypovolemic shock - obstructive shock and acidosis. Poten-

tially fatal pathologies after thoracic trauma are aortic dissection, myocardial contusion, trachea-bronchial laceration, esophageal perforation, massive lung contusion, diaphragmatic laceration with the hernia. Also, airway obstruction, tension and open pneumothorax, cardiac tamponade, massive hemothorax, and flail chest can be life-threatening without emergency intervention. Traumatic diaphragmatic injuries remain a diagnostic challenge. Undiagnosed small diaphragmatic lacerations may lead to serious health problems, such as the herniation, obstruction or strangulation of the abdominal organs to the thorax due to negative pressure in the following period.[3,4] The present study aims to evaluate the role of VATS (Video-Assisted Thoracoscopic Surgery) in the diagnosis and treatment of diaphragmatic injuries after

Cite this article as: Yanık F, Karamustafaoğlu YA, Yörük Y. The role of VATS in the diagnosis and treatment of diaphragmatic injuries after penetrating thoracic traumas. Ulus Travma Acil Cerrahi Derg 2020;26:469-474. Address for correspondence: Fazlı Yanık, M.D. Trakya Üniversitesi Tıp Fakültesi, Göğüs Cerrahisi Anabilim Dalı, 22030 Edirne, Turkey Tel: +90 284 - 235 76 41 / 4416 E-mail: fazliyanik@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):469-474 DOI: 10.14744/tjtes.2019.02682 Submitted: 02.11.2018 Accepted: 29.06.2019 Online: 13.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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penetrating thoracic traumas which cannot be determined by radiologically.

MATERIALS AND METHODS Among 268 penetrating thoracic trauma patients, we retrospectively evaluated a total of 22 patients who performed VATS due to suspected localization for diaphragmatic injury in our department between October 2010 and October 2018. Age, gender, type of trauma, applied treatments, complications and surgical and follow-up outcomes were evaluated. Penetrating traumas (stabbing, rifle gun injury and shotgun injury) suspected for having injured the diaphragm were included in this study. The entrance wound inferior to the nipple line or lower angle of the scapula should be suspected for diaphragmatic injury. We evaluated all patients with chest Xray, computed tomography (with axial, sagittal and coronary sections) and abdominal ultrasonography. Routine hemostasis, hemogram parameters and biochemical blood tests examined. Additionally, the cardiac status of the patients was evaluated by serial serum cardiac enzyme determinations, electrocardiograms, and if need echocardiography. Additional traumatic pathologies were detected, and the patients were treated appropriately. Suspicious cases were prepared for explorative VATS. Patients who had blunt thoracic trauma, patients under 18 years of age, patients performed open surgical procedures, patients with missing data and non-suspect patients were excluded from our study. VATS was performed under general anesthesia with double-lumen intubation. We used L shaped 10 mm 0-degree rigid thoracoscope (Karl-Storz GmbH & Co. Tuttlingen, Germany). After the blood or the hematoma in the thoracic cavity was aspirated, diaphragm, lung, chest wall, the pericardium was explored for possible traumatic pathologies. The detected pathologies were treated with VATS. During VATS, pleural adhesions were dissected using electrocautery or with blunt dissection, if necessary. At the end of the operation, a 0,9% isotonic solution was fulfilled to the thorax, the lung was inflated and air leak control and intrapleural lavage were performed. All the patients were extubated in the operating theater and were followed in the high care unit of our

(a)

service during the first 24 hours. Chest physiotherapy was applied in the early postoperative period. A portable chest Xray was performed after surgery within hours. The chest tube of the cases was removed when there was no air leak, and the chest X-ray of the cases was fully expanded. The patients were discharged on the same day or the next day if their PA roentgenograms were normal after the chest tubes removal. All patients were routinely followed up monthly and yearly in our department.

Data Analysis Statistical analysis was performed using the Statically Package for the Social Science program (SPSS, 20.0). Data were expressed as mean±SD. Frequencies and percentages were used for categorical measures. Student’s t and chi-square tests were used for statistical analysis for the difference between types of penetrating trauma, ages and gender of cases. P<0.05 were considered statistically significant.

RESULTS Twenty-two consecutive cases with suspicious diaphragmatic injury were included in this study. 20 (91%) patients were male and two (9%) patients were female with a mean age of 28.01±6.4 (18–42). In 11 (50%) patients, VATS was performed on the right side (seven of them anterior, four of them posterior hemithorax located), the others on the left side according to penetrating the area of trauma (five of them anterior, six of them posterior hemithorax located) (Figs. 1a, b). All patients underwent uniportal VATS with the help of thoracal applied from the 5th intercostal space. An utility incision was opened in 10 (45%) patients with a diaphragmatic laceration. Eight of these 10 patients (80 %) were localized in left hemithorax and two in the right hemithorax. No herniation was observed in any case (Table 1, Fig. 2). The diaphragm was repaired primary using unabsorbable 0 number non- absorbable sutures in these patients. In six cases (27%) diaphragmatic laceration detected with VATS, pneumothorax (n=2), hemothorax (n=2), pulmonary contusion (n=1) and hemopneumothorax (n=1) were radiologically. The diaphragmatic injury was detected in four patients although no

(b)

Left oblique fissure

Right oblique fissure

Horizontal fissure

Diaphragma

Left oblique fissure Right oblique fissure Diaphragma

Figure 1. Configuration of the penetrating tool entry holes in the (a) anterior (b) posterior hemithorax.

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Table 1. Demographic and clinical characteristics and surgical outcomes of the 22 cases

Table 2. Detected additional traumatic pathologies for the 22 patients

Sex, n (%)

22 (100)

n %

Male

20 (91)

Additional traumatic pathology for thorax

15

68 27.5

Female

2 (9)

Age, mean±SD (range, years) Mean operation time,

28.01±6.4 (18–42) 24.02±4.52 (18–50) minutes

mean±SD (range, min) Mean tube removal time,

1.3±0.5 (1–4) days

mean±SD (range, min) Mean lenght of hospital time,

1.9±0.9 (2–5) days

mean±SD (range, min) Acces of VATS, n (%)

Right*

22 (100) 11 (50)

Left**

11 (50)

Type of penetrating trauma, n (%)

22 (100)

Stabbing

12 (55)

Rifle gun injury

6 (27.5)

Shotgun injury

4 (17.5)

Diaphragmatic laceration detection with VATS, n (%)

Yes

10 (45)

No

12 (55)

Complications, n (%)

2 (9)

Expansion problems

1 (4.5)

Wound infection

1 (4.5)

*7 of them anterior, 4 of them posterior hemithorax located (Figure 1a, b); **5 of them anterior, 6 of them posterior hemithorax located (Figure 1a, b). SD: Standard deviation; VATS: Video-Assisted Thoracoscopic Surgery.

radiological images were found. The missed injury rate was 18%. The specificity, sensitivity, positive predictive value and negative predictive value of VATS were 75%, 71.5%, 60% and 83.3%, respectively, detection of the diaphragm injury after penetrating trauma in our study.

Figure 2. Thoracoscopic view of the diaphragmatic laceration after penetrating trauma in the left anterior hemithorax, 6th intercostal space (Stabbing), marked with a blue arrow.

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Pulmonary contusion

6

Pneumothorax

4 18

Hemothorax

3 13.5

Hemopneumothorax

1 4.5

Pericardial laceration

1

4.5

Additional traumatic pathology for out of thorax

10

45

Liver laceration

4

18

Spleen laceration

3

13.5

Tendon rupture

2

9

Scalp laceration

1

4.5

While conservative treatment was administered in six patients with pulmonary contusion (n=6), tube thoracostomy was performed in patients with pneumothorax (n=4), hemothorax (n=3) and hemopneumothorax (n=1) for another traumatic pathology. Liver laceration (n=4), spleen laceration (n=3), tendon rupture in the forearm (n=2) and scalp laceration (n=1) were the most frequent accompanying injury (Table 2). While all the liver lacerations were treated conservatively, splenectomy was carried out for splenic laceration and tendon cut and scalp wound was repaired by other branches synchronously (Table 2). The mean operation time, chest tube removal time, length of hospital stay time were 24.02±4.52 (18–50) minutes, 1.3±0.5 (1–4) days, 1.9±0.9 (2–5) days, respectively. The mean loss of blood was less than 150 ml. There was no conversion to open thoracotomy and intraoperative complications were not seen. Intraoperative or postoperative mortality was not observed. Complications were developed in two (9%) patients; as expansion problem in one (4.5%) patient and wound infection in one (4.5%) patient. Space was managed successfully with external suction and chest physiotherapy to provide lung expansion. The patient who developed wound infection was treated with broad-spectrum i.v. antibiotics and daily dressing. There was no significant statistical difference between types of penetrating trauma, ages and gender of cases (p>0.05). The mean follow-up period was 36.2±9.3 (range 9–62) months. During this follow-up period, pulmonary function tests and chest X-rays were performed. Clinical changes, recovery and complications were evaluated. No diaphragmatic hernia or traumatic pathology was detected in any patient during the follow-up.

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The other demographic and clinical data and surgical outcomes are summarized in Table 1.

DISCUSSION Thoracic diaphragmatic injury may occur after the blunt thoracic trauma and 15% of penetrating thoracic trauma. It is reported that 2/3 of all diaphragmatic injuries are blunt and 1/3 arises from penetrating trauma. The left side affects more than the right hemithorax.[5,6] In our case series, penetrating thoracic traumas were localized right hemithorax in 11 (50%) patients and left hemithorax in 11 (50%) cases. However, we detected diaphragmatic laceration in 10 out of 22 suspected patients. 80% of these injuries were on the left hemithorax. Diaphragmatic injuries can be divided into three groups as acute, latent and late. Acute diaphragmatic injury is detected within 0–14 days after injury. Latent diaphragmatic injury is diagnosed after acute injury but before intestinal obstruction or strangulation. Late diaphragmatic injury is diagnosed with intestinal obstruction or strangulation. It is difficult to diagnose small diaphragmatic lacerations.[4–6] All of our cases were evaluated with exploratory VATS within 48 hours. No herniation was observed in any case. These cases may show signs of herniation of the abdominal organs to the thorax due to negative intrathoracic pressure and positive intraabdominal pressure after the months or years. Since the abdominal organs such as colon, stomach, spleen and omentum are herniated into the thorax through a small laceration on the diaphragm. This may cause rapid necrosis, sepsis and unexpected death in undiagnosed cases. [5–7] Therefore, we think that exploratory VATS is very important in every suspected case of penetrating trauma. In acute diaphragmatic injury, non-absorbable (0 or 1 number) sutures should be used for primary repair. However, the repair should be supported by prosthetic meshes to strengthen the diaphragm in large defects or chronic cases. [8] The diaphragm was repaired primary using unabsorbable 0 number non-absorbable sutures in 45% of patients with acute diaphragm laceration by penetrating trauma in our study. We did not need prosthetic material. Diaphragm moves between the 4–8 ribs with deep expiration and inspiration. Topographically, penetrating injuries under the 5th intercostal space in the anterior hemithorax and lower end of the scapula in the posterior hemithorax are suspected cases for diaphragmatic laceration. Therefore, diaphragmatic injury should be ruled out in lower of these levels. Otherwise, minor injuries may cause fatal complications in the long term interval.[2,9] Penetrating traumas (stabbing, rifle gun injury and shotgun injury) which suspected for having injured the diaphragm were included in our study. The entrance holes in the area below the 5th intercostal space 472

in the anterior hemithorax and the area under the scapula in the posterior hemithorax were considered as suspected cases. The symptoms of diaphragmatic injury may include shoulder or epigastric pain, severe cough, respiratory distress and intrathoracic bowel sounds. The presence of abdominal symptoms in a person with thoracic injury raises suspicion for diaphragmatic injury. Furthermore, in cases of delayed presentation with chronic herniation, symptoms of partial or complete intestinal obstruction - strangulation may be present.[6,10] All of our cases are asymptomatic. Because of the localization of penetrating injury, exploratory VATS was performed to all of them due to their suspicion of diaphragm injury. In addition to direct X-ray, thoraco-abdominal tomography should be performed in a patient with penetrating trauma who is a suspect diaphragmatic injury. Abnormalities in chest radiography include hemothorax, pneumothorax, hemopneumothorax, the herniated image of the abdominal organ to the thorax or pneumoperitoneum. However, it may not provide any radiological findings.[11] We evaluated all patients using Chest Xray. Full-body computed tomography (with axial, sagittal and coronary sections) and abdominal. We did not detect the herniated image of the abdominal organ to the thorax or pneumoperitoneum. Herniation to the thorax was not seen in our study because of rapid intervention. However, we detected pulmonary contusion in six patients, pneumothorax in four patients, hemothorax in three patients and hemopneumothorax in one patient. In six cases, diaphragmatic laceration was detected with VATS, while additional radiological findings were present. Although no radiological finding was observed in four cases, the diaphragmatic injury was detected. The diagnosis of diaphragm injury can be difficult for trauma surgeons. Using many non-invasive methods, including physical examination, chest X-ray, computed tomography, magnetic resonance imaging and diagnostic peritoneal lavage, a preoperative diagnosis can be obtained only about 70% on time.[12] Paci et al.[13] reported that a diaphragmatic injury in five (38.5%) of 13 patients who had penetrating thoracic trauma. Furthermore, one patient needed conversion from VATS to open operation due to a broad laceration of the diaphragm and diaphragm laceration missed with radiologic methods in the whole of 13 patients in their study. Diaphragmatic lacerations without herniation are difficult to diagnose. We think that VATS is a standard indication for the hemodynamically stable patient who presents with acute penetrating thoracic trauma. In addition to possible accompanying traumatic pathologies, VATS in small diaphragmatic lacerations and accompanying traumatic pathologies are extremely useful both diagnostically and therapeutically. Furthermore, other advantages of VATS were fewer postoperative complications, better postoperative pain control, Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


Yanık et al. The role of VATS in the diagnosis and treatment of diaphragmatic injuries after penetrating thoracic traumas

fewer wound and pulmonary complications, shorter chest tube duration, and a faster return to regular activities compared to thoracotomy.[10–13] Martinez et al.[14] reported missed injury rate in penetrating thoracic trauma is approximately 30%. They take attention that all radiological images can be non-pathological in more than 70% of these patients. We found s missed injury rate as 18%. In properly selected patients, localization penetrating trauma may increase this rate. Pekmezci et al.[15] reported that VATS, which may perform both local anesthesia, or general anesthesia is a safe and effective procedure in the diagnosis and treatment of penetrating thoracoabdominal diaphragmatic injuries. We did not try a diaphragmatic repair with VATS in any patient with the help of local anesthesia in our study.

Conclusion We conclude that the diagnosis of diaphragmatic injuries due to penetrating thoracic trauma is difficult to detect radiologically. Hidden injuries may lead to serious complications in the later period. VATS should be performed for both diagnosis and treatment in suspected penetrating thoracic trauma cases in which the diagnosis cannot be reached by imaging methods. 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.Y., Y.A.K.; Design: F.Y., Y.A.K.; Supervision: Y.A.K., Y.Y.; Fundings: F.Y., Y.Y.; Materials: F.Y., Y.A.K.; Data: F.Y.; Analysis: F.Y., Y.A.K., Y.Y.; Literature search: F.Y., Y.A.K.; Writing: F.Y., Y.A.K., Y.Y.; Critical revision: Y.A.K., Y.Y. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

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REFERENCES 1. Dennis BM, Bellister SA, Guillamondegui OD. Thoracic Trauma. Surg Clin North Am 2017;97:1047–64. 2. Kulshrestha P, Munshi I, Wait R. Profile of chest trauma in a level I trauma center. J Trauma 2004;57:576–81. 3. Paydar S, Johari HG, Ghaffarpasand F, Shahidian D, Dehbozorgi A, Ziaeian B, et al. The role of routine chest radiography in initial evaluation of stable blunt trauma patients. Am J Emerg Med 2012;30:1−4. 4. Okan I, Baş G, Ziyade S, Alimoğlu O, Eryılmaz R, Güzey D, et al. Delayed presentation of posttraumatic diaphragmatic hernia. Ulus Travma Acil Cerrahi Derg 2011;17:435−9. 5. Thiam O, Konate I, Gueye ML, Toure AO, Seck M, Cisse M, et al. Traumatic diaphragmatic injuries: epidemiological, diagnostic and therapeutic aspects. Springerplus 2016;5:1614. 6. Ray MS, Deepak BS, Kumar R. Traumatic diaphragmatic injury: case report. Int Surg J 2016;3:2347−50. 7. Meyers BF, McCabe CJ. Traumatic diaphragmatic hernia. Occult marker of serious injury. Ann Surg 1993;218:783–90. 8. Hanna WC, Ferri LE. Acute traumatic diaphragmatic injury. Thorac Surg Clin 2009;19:485−9. 9. Kumar S, Pol M, Mishra B, Sagar S, Singhal M, Misra MC, et al. Traumatic Diaphragmatic Injury: A Marker of Serious Injury Challenging Trauma Surgeons. Indian J Surg 2015;77:666−9. 10. Hanna WC, Ferri LE, Fata P, Razek T, Mulder DS. The current status of traumatic diaphragmatic injury: lessons learned from 105 patients over 13 years. Ann Thorac Surg 2008;85:1044–8. 11. Iochum S, Ludig T, Walter F, Sebbag H, Grosdidier G, Blum AG. Imaging of diaphragmatic injury: a diagnostic challenge?. Radiographics 2002;22:S103–18. 12. Ochsner MG, Rozycki GS, Lucente F, Wherry DC, Champion HR. Prospective evaluation of thoracoscopy for diagnosing diaphragmatic injury in thoracoabdominal trauma: a preliminary report. J Trauma 1993;34:704–10. 13. Paci M, Ferrari G, Annessi V, de Franco S, Guasti G, Sgarbi G. The role of diagnostic VATS in penetrating thoracic injuries. World J Emerg Surg 2006;1:30. 14. Martinez M, Briz JE, Carillo EH. Video thoracoscopy expedites the diagnosis and treatment of penetrating diaphragmatic injuries. Surg Endosc 2001;15:28–33. 15. Pekmezci S, Kaynak K, Saribeyoğlu K, Memişoğlu K, Kurdal T, Kol E, et al. Thoracoscopy in the diagnosis and treatment of thoracoabdominal stab injuries. Ulus Travma Acil Cerrahi Derg 2007;13:36-42.

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OLGU SERİSİ - ÖZET OLGU SUNUMU

Penetran toraks travmalarından sonra görülebilen diyafragma yaralanmalarının tanı ve tedavisinde VATS’nin rolü Dr. Fazlı Yanık, Dr. Yekta Altemur Karamustafaoğlu, Dr. Yener Yörük Trakya Üniversitesi Tıp Fakültesi, Göğüs Cerrahisi Anabilim Dalı, Edirne

AMAÇ: Penetran torasik travması sonrasında görülebilen diyafragma yaralanmalarının tanısında bazı zorluklar yaşanabilmektedir. Tanı konulamamış küçük diyafragma yaralanmaları, sonraki dönemde ciddi sağlık sorunlarına yol açabilirler. Bu çalışmanın amacı, penetran toraks travması sonrasında görülebilen diyafragma yaralanmalarının tanı ve tedavisinde VATS’nin (Video Yardımlı Torakoskopik Operasyonlar) rolünü değerlendirmektir. GEREÇ VE YÖNTEM: Bu çalışmada, 268 penetran toraks travmalı hasta arasından, Haziran 2008 ile Haziran 2018 tarihleri arasında bölümümüzde diyafragma yaralanması şüphesi ile VATS uygulanan toplam 22 hasta geriye dönük olarak değerlendirildi. BULGULAR: Yirmi (%91) hasta erkek, iki hasta (%9) kadın olup, yaş ortalamaları 28.01±6.4 (18–42) yıldı. Penetran travmanın yerine göre 11 (%50) hastada sağ taraftan, diğerlerine sol taraftan VATS yapıldı. On (%45) hastada diyafragma laserasyonu tespit edildi ve tamir edildi. VATS ile diyafragma laserasyonunun saptanan altı olguda (%27) radyolojik olarak ek travmatik patolojiler saptandı. Radyolojik olarak yaralanmanın atlanma oranı %18’di. VATS’ın özgüllüğü, duyarlılığı, pozitif prediktif değeri ve negatif prediktif değerini sırasıyla %75, %71.5, %60 ve %83.3 olarak hesaplandı. Penetran travma tipleri, yaşları ve cinsiyetleri arasında istatistiksel olarak anlamlı bir fark bulunamadı (p>0.05). 36.2±9.3 (9–62) ve aylık ortalama takip süresince hiçbir komplikasyon görülmedi. TARTIŞMA: Penetran toraks travma sonrası şüpheli izole diyafragma laserasyonu düşünülen, radyolojik olarak belirlenemeyen hemodinamik olarak stabil hastalarda VATS’ın önemli ve uygulanabilir olduğu görüşündeyiz. Anahtar sözcükler: Diyafragma; penetran; torakoskopi; travma. Ulus Travma Acil Cerrahi Derg 2020;26(3):469-474

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doi: 10.14744/tjtes.2019.02682

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CA S E R EP O RT

Transcatheter embolization in pediatric blunt renal trauma: Case report and review of the literature İbrahim Kartal, M.D.,1 Hasan Ali Durmaz, M.D.,2 Sertaç Çimen, M.D.,1 Hamit Ersoy, M.D.1

Sanem Güler Çimen, M.D.,3

1

Department of Urology, Health Sciences University, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara-Turkey

2

Department of Radiology, Health Sciences University, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara-Turkey

3

Department of General Surgery, Health Sciences University, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara-Turkey

ABSTRACT This study aims to evaluate the clinical use and outcomes of transcatheter embolization in the setting of pediatric blunt renal trauma cases using an index case and review of the literature. Although the treatment method selection depends on the grade of the trauma and the hemodynamıc status of the patient, conservative methods are considered initially in the setting of pediatric blunt renal trauma. Transcatheter embolization, which is a relatively conservative treatment option, is commonly utilized in adult blunt renal trauma patient population; however, experience in the pediatric population is scarce. A seven-year-old male patient was admitted due to grade IV renal injury secondary to blunt abdominal trauma. He was conservatively followed until -on the post-trauma day 15- he developed gross hematuria and an unstable hemodynamic status. A renal angiogram was performed, which revealed rightsided renal inferior segmental artery pseudoaneurysm and arterio-venous fistula. Subsequently, a transcatheter embolization was performed. There were no complications and no permanent renal injury. Review of the literature revealed that the success rate of transcatheter embolization is 89.47% in the setting of pediatric blunt abdominal trauma-related renal injury regardless of the renal trauma grade. Four patients underwent nephrectomy due to a failed transcatheter embolization procedure. There are not any patients who suffered from embolization-related complications. These results suggest that transcatheter embolization can be safely performed in children with renal injuries due to blunt abdominal trauma with high success and low complication rates and preservation of renal function. Keywords: Abdominal injuries; aneurysm; child; conservative treatment; kidney.

INTRODUCTION Kidneys are injured in 10–20% of pediatric blunt abdominal trauma cases.[1] These renal injury cases do not usually require surgical interventions and the aim of the therapeutic approach is the preservation of renal function and being as minimally invasive as possible.[2] However, the selection of best treatment option depends on the hemodynamic status of the patient and grade of the renal injury. The scale reported by the American Association for the Surgery of Trauma (AAST) is utilized for grading renal injuries.[3] Although higher AAST grades are more likely to

necessitate surgical treatments, even in the setting of highgrade renal injuries, conservative and/or minimally invasive treatment methods are considered first.[4,5] Transcatheter angioembolization (TAE), which is one of the minimally invasive treatment methods, is performed in case of renal parenchymal lacerations, pseudoaneurysms and arteriovenous fistulas. In this study, we present a case of a renal injury that arises from a pediatric blunt abdominal trauma that later developed pseudoaneurysm and arteriovenous fistula, which were treated by TAE. In addition, we report our literature review results regarding the experience with TAE in the setting of pediatric blunt abdominal trauma-related renal injuries.

Cite this article as: Kartal İ, Durmaz HA, Çimen SG, Çimen S, Ersoy H. Transcatheter embolization in pediatric blunt renal trauma: Case report and review of the literature. Ulus Travma Acil Cerrahi Derg 2020;26:475-481. Address for correspondence: İbrahim Kartal, M.D. Sağlık Bilimleri Üniversitesi, Dışkapı Yıldırım Beyazıt Eğitim ve Araştıma Hastanesi, Üroloji Kliniği, Ankara, Turkey Tel: +90 312 - 596 20 00 E-mail: ibrahimguvenkartal@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):475-481 DOI: 10.14744/tjtes.2019.93043 Submitted: 05.02.2019 Accepted: 10.07.2019 Online: 14.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Kartal et al. Transcatheter embolization in pediatric blunt renal trauma

CASE REPORT A seven-year-old male patient presented to the emergency department 50 minutes after falling off a building. He was hemodynamically stable, conscious and complaining about right-sided flank pain. His past medical and surgical history was unremarkable. He did not have gross hematuria. Physical examination revealed ecchymosis of the right flank region. Complete blood count revealed a hemoglobin level of 14.4 g/ dl. Ultrasonography showed an inferolateral parenchymal laceration in the right kidney accompanied by a 5-cm hematoma. This injury was accepted as AAST grade IV renal trauma. The patient was admitted and conservatively followed for one week. He did not have gross hematuria, hemoglobin decline or any hemodynamic problems during this admission period. One week after his discharge from the hospital, he presented to the emergency department with the complaint of macroscopic hematuria. Physical examination revealed rightsided costovertebral tenderness. His hemoglobin level was measured as 8.5 g/dl. Since he had a previously known right renal parenchymal laceration and hematoma, a renal Doppler ultrasound and a computerized tomography scan were performed. These investigations showed that the hematoma enlarged to 9 cm and there was a 15x12 mm right renal inferior segmental artery pseudoaneurysm associated with an arteriovenous fistula. Renal angiogram performed after transfusion of two units of packed red blood cells confirmed the pseudoaneurysm and arteriovenous fistula (Fig. 1a). During this procedure, the right renal inferior segmental artery was selectively catheterized via a 2.4 F microcatheter (Progreat®, Terumo Medical Corporation, Somerset, New Jersey) and this artery was embolized by 14 various sized detachable coils (Azur®, Terumo Medical Corporation, Somerset,

(a)

New Jersey). The control renal angiogram did not reveal the filling of the pseudoaneurysm and blood flow through the arteriovenous fistula (Fig. 1b). The patient was followed as an inpatient for five days after the intervention, and he was discharged since there were no hemodynamic problems and no hemoglobin decline during this period. Furthermore, no pseudoaneurysm or arteriovenous fistula was detected in the control of renal Doppler ultrasonography. Follow-up evaluation at the sixth month of follow-up included a dimercaptosuccinic acid (DMSA) nuclear renal scan, which showed an area of diminished perfusion, a finding consistent with the embolization of right renal inferior segmental artery. However, the whole right kidney was very well perfused otherwise. The split function of the right kidney was calculated as 35%. Similar findings were detected in the 1-year follow-up visit. The patient is currently on an annual follow-up schedule. Patient’s consent was obtained for this study.

DISCUSSION Trauma is the leading cause of death in children older than one year.[6] In children, kidneys are relatively larger, and they are more mobile. They are located at a lower level in the retroperitoneum; therefore, they are protected less by the ribs when compared with adults. In addition, there is less perinephric fat compared with adult kidneys. As a result, the risk of renal injury is higher in the pediatric population in the setting of blunt abdominal trauma.[7] Management of pediatric blunt renal trauma depends on the hemodynamic status of the patient and the grade of renal injury. Most renal injuries can be followed conservatively. Surgical treatment is needed in approximately 5–10% of these

(b)

Figure 1. (a) Renal angiogram demonstrating the pseudoaneurysm at the right renal inferior segmental artery (red arrow) and arteriovenous fistula (blue arrow). (b) Post-embolization control renal angiogram image.

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1

1

Steffens et al.[39]

F M

3 15

L

R

Fall down Traffic accident

Pseudoaneurysm

Arteriovenous fistula

2003

1

M

11

L

2004

1

Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

2007

2008

Salem et al.[7]

Cannon et al.[42]

1

1

1

Not

Not

Not reported

Not

M

F Not

5

11 Not

L

R Not reported

Fall down

Fall down

reported reported reported

Not

Grade III renal trauma,

Grade IV renal

Pseudoaneurysm

Pseudoaneurysm

Pseudoaneurysm

Grade V renal trauma,

banister Pseudoaneurysm

Falling over a

9

Not reported

21

2

7

1 year

12 day/

1

Not

+

+

+

+

+

+

Time between Renal trauma and salvage diagnosis (day)

2010

2

17 Not

M

5

reported reported

Not

5 Fall down

Traffic accident

L

Traffic accident

M

8

L

Fall down

2013

3

Not

16

Not

Traffic accident

Grade IV renal trauma

Psodoanevrizma

Grade V renal trauma,

Pseudoaneurysm

Grade V renal trauma,

Not reported

10

9

Underwent

+

+

reported

Not

+

+

Not

13

L

Sports injury

Grade IV renal trauma

Not reported

+

Double-J Urinoma

Nephrectomy

Wilms tumor

Nephrectomy for

Re-embolization

Complications/ additional procedures to TAE

Not

14

Not

Sports injury

Grade IV renal trauma

Not reported

Underwent

2013

1

M

17

L

Traffic accident Grade IV renal trauma,

14-28

Not reported

Re-embolization

Nephrectomy

Not

+

+

+

+

reported

Not

+

+

+

+

+

+

+

+

Blood before TAE

2013

1

M

16

L

Sports injury

Yamaçake et al.[45]

Pseudoaneurysm

Grade 3 renal trauma,

1

+

+

Pseudoaneurysm reported

Meissnitzer et al.[38]

reported reported nephrectomy

reported drainage

reported reported nephrectomy

[21]

Schuster et al.

1, 4, 8

Not reported

Not reported

Wilms tumor

Grade IV renal trauma,

Grade V renal trauma

Kicked by horse Grade V renal trauma

reported

Not

L

R

Eassa et al.[2]

3

F

2010

Kiankhooy et al.[44]

M

2009

2

Brewer et al.[43]

reported reported reported trauma reported

2005

Saad et al.[41]

[40]

El-Sherbıny et al.

Halachmi et al.[23]

1996

van der Zee et al.[36] 1995

Author Year Number Gender Age Side Cause of injury Indication of patient (R/L)

Table 1. Studies reported regarding utilization of transcatheter angioembolization in the setting of renal injury due to pediatric blunt abdominal trauma

Kartal et al. Transcatheter embolization in pediatric blunt renal trauma

477


478

cases, and this rate is declining day by day due to increasing the availability of minimally invasive treatment procedures.[8] Surgical treatment is usually preferred in hemodynamically unstable patients or patients with renal vascular pedicle injury, ureteropelvic junction injury or in the setting of failed conservative treatment. Nephrectomy is performed in 60–65% of grade IV or V renal injuries treated surgically.[9] On the other hand, in children with blunt renal trauma, the success rates of conservative treatment are higher when compared with adults.[10] Even in case of grade V renal traumas, an ~80% conservative treatment success ratio was reported.[11–13]

TAE: Transcatheter angioembolization; M: Male; F: Female; R: Right; L: Left.

Wilms tumor

+ Nephrectomy for – 1 Wilms tumor Fall down L 4 M 1 2016 Sweed et al.[47]

reported reported reported reported reported reported reported 2 Nephrectomy reported

reported accident

renal trauma

– + Not reported renal trauma

Traffic 14 M

R

Grade V

Grade III Violence L 15 M

Cabrera et al.[46] 2016 7 Not Not Not Not Not Not Not 1 Endoprosthesis Not

– Not

+

+

+

– – Not Grade III Traffic

accident

L

M

15

renal trauma

reported

+

+ – + Not

reported renal trauma

Grade IV Traffic accident R 16 M 4 2015

Lin et al.[20]

reported reported reported reported reported reported reported reported

Vo NJ et al.[28] 2014 7 Not Not Not Not Not Not Not – Not

Complications/ additional procedures to TAE Time between Renal trauma and salvage diagnosis (day) Author Year Number Gender Age Side Cause of injury Indication of patient (R/L)

Table 1. Studies reported regarding utilization of transcatheter angioembolization in the setting of renal injury due to pediatric blunt abdominal trauma (continuation)

Blood before TAE

Kartal et al. Transcatheter embolization in pediatric blunt renal trauma

The utilization of imaging studies is critical for diagnosis and grading of renal injury.[14] In children with blunt abdominal trauma, imaging studies should be performed in the case of hematuria, abdominal skin ecchymosis, abdominal pain, distention and significant hemoglobin drop. Ultrasonography is the preferred initial imaging modality despite its low efficacy in grading renal injury and its operator-dependence.[15] However, spiral computerized tomography, including non-contrast phase, arterial contrast phase and late phases is more widely used in pediatric cases since it can visualize the renal parenchyma, vascular structures and collecting systems and it can simultaneously view the other abdominal organs.[16] Consequently, computerized tomography has been recommended as the gold standard imaging modality for children presenting with blunt renal trauma.[17] On the other hand, ultrasonography is suggested for periodic follow-up imaging as per ‘as low as reasonably achievable’ (ALARA) principle in order to reduce radiationrelated risks since children are more sensitive to radiation when compared with adults.[17,18] Computerized tomography is preferred during followup only when ultrasonographic imaging reveals any suspicious findings. It has been reported that vascular injuries in the setting of blunt renal traumas can be treated effectively by TAE.[2,19–26] This procedure can be performed in children whose hemodynamic status is either stable or nearly stable and who have active bleeding due to renal parenchymal bleeding, contrast extravasation or perirenal hematoma detected in computerized tomography scan. In addition, it can be utilized in patients with late bleeding following conservative treatment, arterial pseudoaneurysm or arteriovenous fistula. The response of a child to acute bleeding differs from an adult’s response; mental state variations, Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


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hypotension, signs of decreased peripheral perfusion and respiratory changes all occur at a later post-trauma phase compared to adults.[27] Thus, tachycardia without accompanying hypotension can be the first sign of internal hemorrhage. This is significant because pre-TAE blood transfusion rates inversely correlate with the efficacy of TAE.[28,29]

dentally diagnosed by Wilms tumor. Bleeding was controlled by TAE in both cases; however, these patients both underwent nephrectomy afterward under elective circumstances. Two patients reported in the literature required repeat of TAE procedure due to failure at the first attempt; second attempts were successful in both cases (Table 1).[38]

Although renal artery pseudoaneurysm is mostly iatrogenic, it can rarely be due to blunt abdominal trauma.[30] It may cause abdominal tenderness, ecchymosis and/or mass with pulsation at the flank, hematuria, nausea and shock. Rarely, a renal artery pseudoaneurysm may spontaneously get thrombosed and remain asymptomatic for years before it is diagnosed.[31] Usually, the time interval between the blunt abdominal trauma leading to renal artery pseudoaneurysm and the bleeding caused by it (i.e., secondary renal hemorrhage) is in the range of 2–36 days.[32] Our literature review showed that, in children, the time interval between the trauma and diagnosis of renal artery pseudoaneurysm varies from one day to one year (Table 1). Regardless of the time of diagnosis, it can be either conservatively followed or treated by either TAE or open surgery, depending on the clinical status of the patient and the location of the pseudoaneurysm.[33]

Experience gained in the adult patient population shedding light on the TAE applications in pediatric patients and assisted in achieving low complication rates. In addition –for maximum preservation of renal function- selective and even super-selective TAE applications have emerged.[23] As a result, our literature review revealed that –in total- 38 pediatric patients underwent TAE due to blunt renal trauma, and the overall success rate was ~89.5%. Of note, this review also exposed that TAE not only helped in the preservation of the function of the ipsilateral kidney, but it also did not have any impact on the long-term functional status of the contralateral kidney.[40–47]

Rarely, an acquired arteriovenous fistula may occur between the renal arterial and venous systems.[34] These fistulas are usually formed at the right kidney. Although the most common cause is penetrating trauma, these fistulas may also occur as a result of blunt abdominal trauma.[35] However, these patients are usually underdiagnosed during the initial assessment. They may present with renovascular hypertension and/ or congestive heart failure years after the trauma. Kuy et al.[35] and van der Zee et al.[36] reported that renal arteriovenous fistulas, which were previously repaired by open surgery, could be treated by TAE in children with the benefit of preserving renal function. The complication profile of TAE is similar between children and adults; however, complication rates are lower in the former group.[2] Formation of hematoma in the arterial access site, arterial injury due to catheter or guidewire, contrast nephropathy, renal ischemia (i.e., target organ ischemia) and embolization of the non-targeted organ are the potential complications of TAE in children.[37] Renal artery dissection is detected in 7.5% of the adult patient population as a complication of TAE; this complication has never been encountered in children. Complications and/or failure of TAE can occasionally necessitate additional interventions. Our literature review revealed that four patients underwent nephrectomy due to failure. One patient who experienced urinary extravasation needed double J stent and urinoma drainage catheter insertion. In another patient, endoprosthesis placement was performed for renal revascularization. Two patients who were evaluated due to blunt renal trauma following falling off a height were inciUlus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

Conclusion The risk of exposure to blunt abdominal trauma-related renal injury is significantly higher in children than adults. In hemodynamically stable patients, conservative or non-surgical treatment methods are preferred since they eliminate the potential risks of emergent surgery, preserve the functionality of the target organ and provide favorable long-term results. In our index case, we treated both the renal pseudoaneurysm and arteriovenous fistula, which caused posttrauma renal bleeding successfully by TAE. This patient did not experience any complications or renal function decline during follow-up. As such, our literature review showed that –although the experience in children is not extensive- TAE can be safely and successfully performed in the pediatric blunt renal trauma population. No long-term complications of TAE were reported except for the cases which required nephrectomy following a failed TAE. Of note, ‘TAE failure’ itself is not the reason for nephrectomy in these cases. Informed Consent: Written informed consent was obtained from the parents of the patient for the publication of the case report and the accompanying images. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: İ.K., H.A.D.; Design: İ.K., H.A.D; Supervision: S.G.Ç., S.Ç.; Materials: İ.K., H.A.D., H.E.; Data: İ.K., H.A.D.; Analysis: İ.K.; Literature search: İ.K., S.G.Ç.; Writing: İ.K., S.Ç.; Critical revision: İ.K., S.G.Ç., H.E. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

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23. Halachmi S, Chait P, Hodapp J, Bgli DG, McLorie GA, Khoury AE, et al. Renal pseudoaneurysm after blunt renal trauma in a pediatric patient: management by angiographic embolization. Urology 2003;61:224. 24. van der Vlies CH, Olthof DC, van Delden OM, Ponsen KJ, de la Rosette JJ, de Reijke TM, et al. Management of blunt renal injury in a level 1 trauma centre in view of the European guidelines. Injury 2012;43:1816−20. 25. Breyer BN, McAninch JW, Elliott SP, Master VA. Minimally invasive endovascular techniques to treat acute renal hemorrhage. J Urol 2008;179:2248–53. 26. Puapong D, Brown CV, Katz M, Kasotakis G, Applebaum H, Salim A, et al. Angiography and the pediatric trauma patient: a 10-year review. J Pediatr Surg 2006;41:1859−63. 27. Hamner CE, Groner JI, Caniano DA, Hayes JR, Kenney BD. Blunt intraabdominal arterial injury in pediatric trauma patients: injury distribution and markers of outcome. J Pediatr Surg 2008;43:916–23. 28. Vo NJ, Althoen M, Hippe DS, Prabhu SJ, Valji K, Padia SA. Pediatric abdominal and pelvic trauma: safety and efficacy of arterial embolization. J Vasc Interv Radiol 2014;25:215–20. 29. Dente CJ, Shaz BH, Nicholas JM, Harris RS, Wyrzykowski AD, Patel S, et al. Improvements in early mortality and coagulopathy are sustained better in patients with blunt trauma after institution of a massive transfusion protocol in a civilian level I trauma center. J Trauma 2009;66:1616−24. 30. Farrell TM, Sutton JE, Burchard KW. Renal artery pseudoaneurysm: a cause of delayed hematuria in blunt trauma. J Trauma 1996;41:1067–8. 31. Lee RS, Porter JR. Traumatic renal artery pseudoaneurysm: diagnosis and management techniques. J Trauma 2003;55:972–8. 32. Heyns CF, de Klerk DP, de Kock ML. Stab wounds associated with hematuria--a review of 67 cases. J Urol 1983;130:228–31. 33. Teigen CL, Venbrux AC, Quinlan DM, Jeffs RD. Late massive hematuria as a complication of conservative management of blunt renal trauma in children. J Urol 1992;147:1333–6. 34. Wright JL, Porter JR. Renal artery pseudoaneurysm after laparoscopic partial nephrectomy. Urology 2005;66:1109. 35. Kuy S, Rossi PJ, Seabrook GR, Brown KR, Lewis BD, Rilling WS, et al. Endovascular management of a traumatic renal-caval arteriovenous fistula in a pediatric patient. Ann Vasc Surg 2014;28:1031.e1-5. 36. van der Zee JA, van den Hoek J, Weerts JG. Traumatic renal arteriovenous fistula in a 3-year-old girl, successfully treated by percutaneous transluminal embolization. J Pediatr Surg 1995;30:1513–14. 37. Corr P, Hacking G. Embolization in traumatic intrarenal vascular injuries. Clin Radiol 1991;43:262–4. 38. Meissnitzer T, Hruby S, Janetschek G, Meissnitzer MW. Recurrence of a Delayed-Onset Posttraumatic Renal Pseudoaneurysm after Initially Successful Transarterial Embolization. Urol Int 2017;98:245–8. 39. Steffens MG, Bode PJ, Lycklama à Nijeholt AA, van Vugt AB. Selective embolization of pseudo-aneurysms of the renal artery after blunt abdominal injury in a patient with a single kidney. Injury 1996;27:219–20. 40. El-Sherbiny MT, Aboul-Ghar ME, Hafez AT, Hammad AA, Bazeed MA. Late renal functional and morphological evaluation after non-operative treatment of high-grade renal injuries in children. BJU Int 2004;93:1053−6. 41. Saad DF, Gow KW, Redd D, Rausbaum G, Wulkan ML. Renal artery pseudoaneurysm secondary to blunt trauma treated with microcoil embolization. J Pediatr Surg 2005;40:e65–7. 42. Cannon GM Jr, Polsky EG, Smaldone MC, Gaines BA, Schneck FX, Bellinger MF, et al. Computerized tomography findings in pediatric renal trauma--indications for early intervention? J Urol 2008;179:1529−33. 43. Brewer ME Jr, Strnad BT, Daley BJ, Currier RP, Klein FA, Mobley JD, et al. Percutaneous embolization for the management of grade 5 renal trauma in hemodynamically unstable patients: initial experience. J Urol

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44. Kiankhooy A, Sartorelli KH, Vane DW, Bhave AD. Angiographic embolization is safe and effective therapy for blunt abdominal solid organ injury in children. J Trauma 2010;68:526–31.

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2009;181:1737−41.

OLGU SUNUMU - ÖZET OLGU SUNUMU

Pediatrik künt renal travmalarda transkateter embolizasyon: Olgu sunumu ve literatür derlemesi Dr. İbrahim Kartal,1 Dr. Hasan Ali Durmaz,2 Dr. Sanem Güler Çimen,3 Dr. Sertaç Çimen,1 Dr. Hamit Ersoy1 1 2 3

Sağlık Bilimleri Üniversitesi, Dışkapı Yıldırım Beyazıt Eğitim ve Araştıma Hastanesi, Üroloji Kliniği, Ankara Sağlık Bilimleri Üniversitesi, Dışkapı Yıldırım Beyazıt Eğitim ve Araştıma Hastanesi, Radyoloji Kliniği, Ankara Sağlık Bilimleri Üniversitesi, Dışkapı Yıldırım Beyazıt Eğitim ve Araştıma Hastanesi, Genel Cerrahi Kliniği, Ankara

Bu yazıda, pediatrik olgularda künt abdominal travma sonucu gelişen renal yaralanmaların tedavisinde transkateter embolizasyon kullanımı ve sonuçları, bir olgu ve literatür eşliğinde değerlendirildi. Abdominal künt travma sonrası çocuklarda renal yaralanma gerçekleşmesi durumunda tedavi tercihi renal travmanın derecesine ve hastanın hemodinamisine bağlı olmakla birlikte, tedavide mümkün olduğunca non-operatif yöntemlerin kullanılması önerilmektedir. Transkateter embolizasyon kullanımı erişkinlerde renal yaralanmalarda pratikte yaygın olarak kullanılırken, çocuklarda kullanımı ile ilgili deneyim azdır. Yedi yaşında erkek hastada künt abdominal travma ve buna bağlı olarak gelişen grade IV renal yaralanma nedeniyle takibe alındı. Konservatif yöntemlerle takip edilen hastada travma sonrası 15. günde hematüri ve hemodinamide bozulma gerçekleşti. Renal anjiyografide; sağ inferior segmental arterde psödoanevrizma ve arteriyovenöz fistül saptandı. Hastaya transkateter embolizasyon başarılı şekilde uygulandı, herhangi bir komplikasyon olmadığı gibi renal hasarda görülmedi. Literatür değerlendirmesinde pediatrik künt abdominal travma sonrası renal yaralanama nedeniyle yapılan transkateter embolizasyonun renal yaralanma derecesine bakılmaksızın başarı oranı %89.47’dir. Transkateter embolizasyon başarısızlığı nedeniyle dört hastada nefrektomi yapılmış, hiçbir hastada uzun dönemde komplikasyon gözlenmemiştir. Bu sonuçlar eşliğinde çocuklarda, künt abdominal travma sonrası renal yaralanmaların transkateter embolizasyon ile tedavisinde; düşük komplikasyon ile yüksek başarı bildirilmekte ve uzun dönemde renal fonksiyonun korunmasında da güvenilir bir yöntem olduğu anlaşılmaktadır. Anahtar sözcükler: Abdominal travma; anevrizma künt; böbrek; çocuk; konservatif tedavi. Ulus Travma Acil Cerrahi Derg 2020;26(3):475-481

doi: 10.14744/tjtes.2019.93043

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Surgical approach for acute ischemic colitis after scuba diving: A case report Eun Soo Choi, M.D.,1

Han Deok Kwak, M.D.,2

Jae Kyun Ju, M.D.2

1

Department of General Surgery, KS Hospital, Gwangju-Korea

2

Division of Colorectal Surgery, Department of General Surgery, Chonnam National University Hospital, Gwangju-Korea

ABSTRACT The clinical manifestations that may occur due to decompression during scuba diving vary widely, but only mild symptoms have been reported mainly in the gastrointestinal tract. In particular, ischemic colitis caused by air embolism is rare.We report a case of full-thickness ischemic colitis treated with failed conservative treatment but successfully treated surgically. The case that was presented here suggests that decompression after scuba diving may cause severe symptoms in the gastrointestinal tract and may require a surgical approach. Treatment depends on the severity of the symptoms and the patient’s condition, but surgical approaches should be considered. Keywords: Acute ischemic colitis; air embolism; decompression sickness; scuba diving; surgical approach.

INTRODUCTION The incidence of decompression sickness after scuba diving has been reported to be 1.27 to 1.52 per 1000 dives,[1] and >1,000 diving-related injuries are reported annually.[2] When pulmonary barotrauma or decompression sickness occurs, gas bubbles may form and enter the systemic circulation, causing embolization or organ ischemia. Such air embolism may damage musculoskeletal, cutaneous, lymphatic, and neurological systems.[3] Approximately 13% of the divers develop aerophagia at the time of ascent and complain of gastrointestinal symptoms.[4] The main complaints include symptoms of abdominal pain, nausea, vomiting, and abdominal distension. Gastrointestinal barotrauma has been reported, though rarely, to cause serious gastrointestinal symptoms, such as gastric perforation or small bowel infarction due to thrombosis.[5,6] Hyperbaric oxygen therapy and other conservative therapies are usually effective, but may sometimes cause serious symptoms due to air embolism.[7]

Air embolism may cause ischemic colitis, but it is rare. Here, we report a case of surgical treatment of full-thickness ischemic colitis due to air embolism.

CASE REPORT A 58-year-old man visited our emergency department with diffuse abdominal pain and bloody diarrhea two days before his admission to our emergency department. The patient was a skilled diver who caught seafood by diving for 30 years. Two days before, he experienced severe abdominal pain after diving for two hours at a depth of 30 m. He was immediately transferred to a local hospital and received hyperbaric oxygen therapy for two days. However, his symptoms did not improve, so he was referred to our emergency department. His medical history indicated no underlying disease. At the time of admission, he was normotensive and afebrile, and his pulse rate was 120/min and respiratory rate was 20/min. Physical examination revealed diffuse abdominal tenderness, mild abdominal distension, and anuria. The initial laboratory findings were as follows: white blood cell count, 2.7 × 103/μL;

Cite this article as: Choi ES, Kwak HD, Ju JK. Surgical approach for acute ischemic colitis after scuba diving: A case report. Ulus Travma Acil Cerrahi Derg 2020;26:00-00 Address for correspondence: Jae Kyun Ju, M.D. Jebongro 42, Dongu 61469 Gwangju - South Korea Tel: 8201089911504 E-mail: eschoi83@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):00-00 DOI: 10.14744/tjtes.2019.67523 Submitted: 26.12.2018 Accepted: 06.02.2019 Online: 25.02.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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(a)

(b) Figure 1. Sigmoidoscopy. Diffuse huge ulcerative lesion and mucosal swelling in the mid rectum to the mid sigmoid colon.

Figure 3. A: Terminal ileum; B: Colon. (a) Thinning mucosa, fat necrosis, infiltration of inflammatory cells, and necrosis of serosa showing typical transmural infarct findings. (b) Mucosa crypt necrosis, inflammatory cell infiltration across all layers, and serosa suppurative inflammation and abscess showing typical necrotizing inflammation.

Figure 2. Resected specimen. Resected specimen showing multifocal necrosis in the terminal ileum, colon and rectum.

blood urea nitrogen (BUN)/creatinine (Cr) level, 87.6/4.99 mg/dL; C-reactive protein (CRP) level, 33.9 mg/dL; lactate level, 3.32 mg/dL and creatine kinase 1267 IU/L. Other laboratory findings, including coagulation and urinalysis profiles, were within the normal ranges. Elevated serum creatinine level and anuria were detected, and continuous renal replacement therapy (CRRT) was initiated under the diagnosis of sepsis-induced acute renal failure. Nonenhanced abdomen computerized tomography (CT) and high-resolution chest CT were performed. Abdominal CT revealed no specific finding except mild small bowel ileus. Chest CT revealed centrilobular emphysema in both the upper Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

lungs and atelectasis in both lower lungs. After admission to the intensive care unit, on follow-up abdominal computerized tomography angiography (ACTA), the terminal ileum, ascending and sigmoid colon, and rectum showed decreased enhancement and wall thickening with inflammatory infiltration of surrounding tissue. Emergency sigmoidoscopy was performed, and continuous diffuse huge ulcerative lesions and ischemic changes were observed from the mid rectum to the mid sigmoid colon (Fig. 1). The severe abdominal pain persisted on physical examination, the contrast of the terminal ileum on ACTA diminished, and an ischemic change was confirmed on sigmoidoscopy to determine the emergency operation. The intraoperative findings showed small bowel necrosis from the terminal ileum to approximately 40 cm of the proximal ileum, necrotic changes of the mesentery, and focal serosal necrosis over the whole colon, including the sigmoid colon (Fig. 2). Finally, a temporary ileostomy was performed after subtotal colectomy. Pathological findings showed a diffuse mural infarct with serosal 483


Choi et al. Surgical approach for acute ischemic colitis after scuba diving

abscess formation in the colon and a transmural infarct in the terminal ileum (Fig. 3).

rarely diagnosed as ischemic colitis after diving and extremely rarely progresses to full-thickness necrosis.[14]

He had decreased serum creatinine level on postoperative day 1, the abdominal pain disappeared on postoperative day 2, and his serum creatinine level returned to its normal level in urine output and the renal replacement was discontinued on postoperative day 3. On the 10th day after surgery, he was discharged without any abnormal findings.

Conclusion

DISCUSSION Ischemic colitis can be diagnosed accurately by combining history-taking; physical, laboratory, radiological, and endoscopic examinations; and biopsy. Our patient’s medical history indicated no thrombotic events, and blood tests or other specific evaluations revealed no coagulopathy of any type. Therefore, we estimated the cause of the vascular obstruction and venous infarction to be decompression sickness after scuba diving. Owing to the absence of an underlying disease treated with hyperbaric oxygen therapy, we performed conservative management through intravascular fluid resuscitation, use of broad-spectrum antibiotics, and continuous renal replacement therapy and close monitoring. However, diagnostic laparotomy was performed because of severe abdominal pain, follow-up abdominal CT and ischemic change on colonoscopy. As a diver descends into the water and breathes under elevated pressure, the amounts of oxygen and nitrogen in the tissues increase according to Henry’s law. When the diver returns to the surface, the sum of the gas tension in the tissue exceeds the ambient pressure and releases the free gas in bubble form.[8] The bubbles may have diverse and complex effects on the body from direct obstruction of blood flow, disturbance of lymphatic flow, direct stimulation, or nerve damage by inflammatory mediators. These effects can be mild, cause sensory abnormalities, and in severe cases, lead to paralysis and death.[9] The primary treatment for decompression sickness is recompression in a hyperbaric chamber and breathing with 100% oxygen.[10] This process brings on a large diffusion gradient that reduces the rate of new bubble formation and reduces the size of existing bubbles.[11] Appropriate treatment of decompression sickness is usually effective; especially when starting early after injury, the residual effect is unremarkable. Most residual effects resolve over time, but some residual effects may be permanent.[12] Air embolism may cause ischemic colitis by reducing blood flow through the mesenteric vasculature. Ischemic colitis can be divided into two groups, full-thickness with gangrene and partial thickness (mucosa and submucosa). Full-thickness is temporary in most cases and can be managed with conservative therapy without causing full-thickness necrosis.[13] It is 484

Even after hyperbaric oxygen therapy for decompression sickness after scuba diving, ischemic colitis may occur by air embolism. If the symptoms are consistent with ischemic colitis after diving, comprehensive physical, laboratory, and radiologic examinations are required. Treatment depends on the severity of the symptoms and the patient’s condition, but it is important to consider surgical approaches. Informed Consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Ethics Approval and Consent to Participate: This case report was approved by the Institutional Review Board (IRB). IRB No. CNUH-EXP-2018-287. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: E.S.C., J.K.J.; Design: E.S.C.; Supervision: E.S.C.; Fundings: J.K.J.; Materials: E.S.C.; Data: E.S.C., J.K.J., H.D.K.; Analysis: E.S.C., H.D.K.;; Literature search: E.S.C.; Writing: E.S.C.; Critical revision: J.K.J., H.D.K. Conflict of Interest: None declared. Financial Disclosure: The autors declared that this study has received no financial support.

REFERENCES 1. Hagberg M, Ornhagen H. Incidence and risk factors for symptoms of decompression sickness among male and female dive masters and instructors-a retrospective cohort study. Undersea Hyperb Med 2003;30:93–102. 2. Newton HB. Neurologic complications of scuba diving. Am Fam Physician 2001;63:2211–18. 3. Sun Q, Gao G. Decompression Sickness. N Engl J Med 2017;377:1568. 4. Lundgren CE, Ornhagen H. Nausea and abdominal discomfort--possible relation to aerophagia during diving: an epidemiologic study. Undersea Biomed Res 1975;2:155–60. 5. Hunter JD, Roobottom CA, Bryson PJ, Brown C. Conservative management of gastric rupture following scuba diving. J Accid Emerg Med 1998;15:116–7. 6. Gertler SL, Stein J, Simon T, Miyai K. Mesenteric venous thrombosis as sole complication of decompression sickness. Dig Dis Sci 1984;29:91–5. 7. Tetzlaff K, Shank ES, Muth CM. Evaluation and management of decompression illness--an intensivist’s perspective. Intensive Care Med 2003;29:2128–36. 8. Barratt DM, Harch PG, Van Meter K. Decompression illness in divers: a review of the literature. Neurologist 2002;8:186–202. 9. Vann RD, Butler FK, Mitchell SJ, Moon RE. Decompression illness. Lancet 2011;377:153–64. 10. Cianci P, Slade JB Jr. Delayed treatment of decompression sickness with short, no-air-break tables: review of 140 cases. Aviat Space Environ Med 2006;77:1003–8. 11. Hyldegaard O, Møller M, Madsen J. Effect of He-O2, O2, and N2O-O2 breathing on injected bubbles in spinal white matter. Undersea Biomed Res 1991;18:361–71. 12. Thalmann ED. Principles of US NAVY recompression treatments for decompression sickness. In: Bennett PB, Moon RE, eds. Proceedings

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Colon Rectal Surg 2012;25:228–35. 14. Payor AD, Tucci V. Acute ischemic colitis secondary to air embolism after diving. Int J Crit Illn Inj Sci 2011;1:73–8.

OLGU SUNUMU - ÖZET

Tüplü dalış sonrası gelişen akut iskemik kolit için cerrahi yaklaşım: Olgu sunumu Dr. Eun Soo Choi,1 Dr. Han Deok Kwak,2 Dr. Jae Kyun Ju2 1 2

KS Hastanesi, Genel Cerrahi Kliniği, Gwangju-Kore Chonnam Ulusal Üniversite Hastanesi, Genel Cerrahi Bölümü, Kolorektal Cerrahi Bölümü, Gwangju, Kore

Tüplü dalış sırasında dekompresyon nedeniyle ortaya çıkabilecek klinik belirtiler büyük ölçüde değişmekle birlikte esas olarak gastrointestinal sistemde sadece hafif semptomlar bildirilmiştir. Özellikle, hava embolisinin neden olduğu iskemik kolit nadirdir. Biz başarısız konservatif tedavi uygulanan ancak cerrahi olarak başarılı bir şekilde tedavi edilen tam kalınlıkta iskemik kolit olgusunu sunuyoruz. Bildirdiğimiz hususlar tüplü dalıştan sonra dekompresyonun gastrointestinal sistemde ciddi semptomlara neden olabileceğini ve cerrahi bir yaklaşım gerektirebileceğini düşündürmektedir. Tedavi semptomların şiddetine ve hastanın durumuna bağlı olmakla birlikte cerrahi yaklaşımlar düşünülmelidir. Anahtar sözcükler: Akut iskemik kolit; cerrahi yaklaşım; dekompresyon hastalığı; hava embolisi; tüplü dalış. Ulus Travma Acil Cerrahi Derg 2020;26(3):482-485

doi: 10.14744/tjtes.2019.67523

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Rhinoceros-related delayed traumatic diaphragmatic rupture Michael Sebastian, M.D.,1 Alia Abdullah, M.D.,1 Mohamed Abusharia, M.D.,1 Fikri M Abu-Zidan, M.D.2 1

Department of Surgery, Al-Ain Hospital, Al-Ain-United Arab Emirates

2

Department of Surgery, College of Medicine and Health Sciences, UAE University, Al-Ain-United Arab Emirates

ABSTRACT Animal-related injuries should be analyzed based on the behavior and anatomy of the attacking animal. Rhinoceros-related injuries in humans are extremely rare. Hereby, we report a life-threatening traumatic diaphragmatic hernia in a woman who presented three years after a rhinoceros gored her chest. A 47-year-old lady presented with abdominal pain, bilious vomiting and obstipation of one-day duration. She had recurrent attacks of colicky abdominal pain for a week before that. The patient gave the history of being admitted to the ICU three years before, after being gored by a rhinoceros into her chest while working as a veterinary assistant in the zoo. On examination, the abdomen was distended but soft and lax. Bowel sounds were exaggerated. Abdominal x-rays showed multiple air-fluid levels. A gastrographin follow through study hold up in the small bowel and did not reach the colon after seven hours. Abdominal and chest CT scan showed the splenic colonic flexure to be located in the left chest through a left diaphragmatic hernia. Urgent laparotomy showed a healthy splenic flexure of the colon that herniated through a 4 cm postero-lateral defect in the left diaphragm.The colon was reduced, and the defect was repaired with non-absorbable sutures. Postoperative recovery was smooth. The patient was discharged home 10 days after the surgery. Rhinoceros-related injuries in humans are extremely rare. Life-threatening traumatic diaphragmatic herniation may be delayed for few years. High index of suspicion is needed for its diagnosis. Keywords: Injury; rhinoceros; rupture diaphragm; trauma.

INTRODUCTION

CASE REPORT

Rhinoceros-related injuries of humans are extremely rare. In general, animal-related injuries should be analyzed based on the behavior and anatomy of the attacking animal.[1,2] Although rhinoceroses cause approximately 20% of human injuries,[3] and 30% of the human fatalities related to wildlife animal attacks,[4] very little is known about the mechanism of these injuries. There is only one case report in the literature describing this mechanism.[5] Herein, we report a life-threatening traumatic diaphragmatic hernia in a woman who presented three years after a rhinoceros gored her chest.

A 47-year-old woman presented to the Emergency Department of Al-Ain Hospital with acute abdominal pain, bilious vomiting and obstipation of one-day duration. She had mild recurrent attacks of colicky abdominal pain for one week. The patient gave a history of being admitted to an Intensive Care Unit, three years before, after being gored by a white rhinoceros into her chest while working as a veterinary assistant in the zoo. She sustained left hemothorax and multiple left rib fractures, which needed chest tube drainage. The patient had a history of appendectomy during her childhood. On examination, the abdomen was distended but soft and

Cite this article as: Sebastian M, Abdullah A, Abusharia M, Abu-Zidan FM. Rhinoceros-related delayed traumatic diaphragmatic rupture. Ulus Travma Acil Cerrahi Derg 2020;26:486-488. Address for correspondence: Fikri M Abu-Zidan, M.D. POBox 17666 AL-Ain - United Arab Emirates. Tel: 0097137137579 E-mail: fabuzidan@uaeu.ac.ae Ulus Travma Acil Cerrahi Derg 2020;26(3):486-488 DOI: 10.14744/tjtes.2019.73857 Submitted: 15.04.2019 Accepted: 29.05.2019 Online: 14.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Figure 1. (a) Erect abdominal X-ray showing air-fluid levels (black arrows). A gas-filled structure with haustrations that is continuous with the abdomen (arrowheads) reaches above the left diaphragm suggesting a left diaphragmatic hernia containing part of the colon. (b) An erect chest X-ray taken at the same time showing healed old rib fractures (yellow arrow) with callus formation, air-fluid levels within the colon (black arrows), and compressed lung (arrowheads).

lax. Bowel sounds were exaggerated. Abdominal X-rays showed multiple air-fluid levels and gas-filled structure with haustrations above the left diaphragm, suggesting a left diaphragmatic hernia containing part of the colon (Fig. 1a). Erect chest X-ray taken at the same time showed healed old

rib fractures with callus formation, air-fluid levels within the colon, and compressed lung (Fig. 1b). A gastrografin followthrough study, hold up in the transverse colon and did not reach the descending colon after seven hours. The abdominal and chest CT scan showed the splenic flexure of the colon to be in the left chest through a left diaphragmatic hernia (Fig. 2). Urgent laparotomy showed a healthy splenic flexure of the colon that herniated through a 4 cm postero-lateral defect in the left diaphragm. The colon was reduced, and the defect was repaired with non-absorbable sutures. Postoperative recovery was smooth. The patient was discharged home 10 days after surgery. The patient gave her written consent to publish her medical data with the understanding that her identity shall remain confidential.

DISCUSSION

Figure 2. Coronal reconstruction of abdominal CT scan with intravenous and oral contrast showing dilated small bowel (yellow arrows) and transverse colon, and a herniated left splenic flexure of the colon (arrowheads) through the left diaphragm. There was no dye seen in the descending or sigmoid colon.

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Animal-related injuries should be analyzed depending on the anatomy and behavior of the attacking animal. The rhinoceros is historically connected to head and neck surgery. The first parathyroid gland was discovered by Sir Richard Owen in 1849 by dissecting a rhinoceros in London Zoological Gardens.[6] Rhinoceroses are large animals reaching up to 3800 kg in weight. They can be seriously aggressive and dangerous even with the slightest provocation because they have poor vision.[5,7] Both the Indian and African rhinoceroses have 20– 100 cm long single horns that are used as lethal weapons.[5] Accordingly, rhinoceroses have no natural predators.[6] Male rhinoceroses protect their exclusive non-overlapping territories that they mark by the smell of their own urine and stool. [7,8] Dominant male rhinoceroses wipe their horns to trees or 487


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ground and then attack each other from a distance by touching their horns while their heads and ears are raised up.[7,9] The reaction of rhinoceros to humans varies. It depends mainly on sensory responses. The animal usually prefers not to attack humans but to run for a few hundred meters before stopping.[8] The rhinoceros-related human injury, which was reported by Shah et al.,[5] was mainly a goring penetrating chest injury that caused a large left open wound. Our patient presented with a life-threatening left traumatic diaphragmatic hernia three years after the initial rhinoceros-related injury. Our patient was also injured in the chest, possibly because the chest was at the level of the rhinoceros’ horn. We have previously reported that the chest was the most common injured human region following camel kicks. We attributed that to the height of the camel kick.[10] Rhinoceroses may also bite humans by the incisors of their lower jaw if humans closely approach them.[8] Our patient presented with a clinical picture of mechanical intestinal obstruction. The patient had a history of appendectomy, raising the suspicion of adhesive intestinal obstruction. However, properly reading the abdominal and chest X-rays, and correlating it with the associated history of severe chest trauma, directed us to the diagnosis of delayed diaphragmatic hernia.

Conclusion Rhinoceros-related injuries in humans are extremely rare. Life-threatening traumatic diaphragmatic herniation may be delayed for a few years. The high index of suspicion is needed for its diagnosis. Informed Consent: The patient gave her written consent to publish her medical data with the understanding that her

identity shall remain confidential. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: M.S., A.A., M.A., F.A.Z. Design: M.S., A.A., M.A., F.A.Z. Supervision: F.A.Z.; Materials: M.S., A.A., M.A.; Data: M.S., A.A., M.A.; Analysis: M.S., A.A., M.A., F.A.Z. Literature search: F.A.Z.; Writing: F.A.Z.; Critical revision: M.S., A.A., M.A., F.A.Z. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Abu-Zidan FM, Eid HO, Hefny AF, Bashir MO, Branicki F. Camel bite injuries in United Arab Emirates: a 6 year prospective study. Injury 2012;43:1617–20. 2. Abu-Zidan FM. Crossroad between camel bites and crocodile bites. Afr Health Sci 2015;15:i–iv. 3. Acharya KP, Paudel PK, Neupane PR, Köhl M. Human-Wildlife Conflicts in Nepal: Patterns of Human Fatalities and Injuries Caused by Large Mammals. PLoS One 2016;11:e0161717. 4. Silwal T, Kolejka J, Sharma RP. Injury Severity of Wildlife Attacks on Humans in the Vicinity of Chitwan National Park, Nepal. J Biodivers Manage Forestry 2016; 5:1. 5. Shah S, Marharjan N, Pradhan S, Kafle P, Chapagain D, Reddy D. A lethal chest injury following rhinoceros attack– a case report. J College Med Sciences-Nepal 2012;8:52−5. 6. Felger EA, Zeiger MA. The death of an Indian Rhinoceros. World J Surg 2010;34:1805–10. 7. Owen-Smith N. Territoriality in the white rhinoceros (Ceratotherium simum) Burchell. Nature 1971;231:294–6. 8. Hutchins M, Kreger MD. Rhinoceros behavior: implications for captive management and conservation. Int Zoo Yb 2006;40:150–73. 9. Yadav VK. Male-male Aggression in Rhinoceros Unicornis- An observation from North Bengal, India. Zoo’s Print J 2000;15:328−30. 10. Abu-Zidan FM, Hefny AF, Eid HO, Bashir MO, Branicki FJ. Camelrelated injuries: prospective study of 212 patients. World J Surg 2012;36:2384–9.

OLGU SUNUMU - ÖZET

Gergedanın neden olduğu gecikmiş travmatik diyafragma rüptürü Dr. Michael Sebastian,1 Dr. Alia Abdullah,1 Dr. Mohamed Abusharia,1 Dr. Fikri M Abu-Zidan2 1 2

Al-Ain Hastanesi, Genel Cerrahi Bölümü, Al-Ain-Birleşik Arap Emirlikleri BAE Üniversitesi Tıp ve Sağlık Bilimleri Koleji, Genel Cerrahi Anabilim Dalı, Al-Ain-Birleşik Arap Emirlikleri

Hayvanların neden olduğu yaralanmalar, saldıran hayvanın davranışına ve anatomisine dayanarak analiz edilmelidir. İnsanlarda gergedanla ilgili yaralanmalar son derece nadirdir. Bu vesileyle, bir gergedan tarafından göğsünden boynuz darbesi aldıktan üç yıl sonra başvuran kadın hastada yaşamı tehdit eden travmatik diyafragma hernisi olgusunu bildiriyoruz. Kırk yedi yaşında kadın hasta karın ağrısı, safralı kusma ve bir günlük obstipasyon ile başvurdu. Önceden bir hafta boyunca tekrarlayan kolik tarzında karın ağrısı atakları geçirmişti. Hastadan üç yıl önce hayvanat bahçesinde veteriner asistanı olarak çalışırken göğsüne bir gergedan tarafından boynuz darbesi aldığını ve yoğun bakım ünitesine kabul edildiği öğrenildi. Muayenede karın şişkin, yumuşak ve gevşekti. Bağırsak sesleri abartılıydı. Batın grafileri çoklu hava sıvı seviyeleri gösterdi. Röntgen çekimi sırasında takip edilen gastrografin kontrast maddesi ince bağırsakta takılıp kaldı ve yedi saat sonra bile kolona ulaşmadı. Abdominal ve torasik bilgisayarlı tomografi taraması, kolonun splenik fleksurasının sol göğüste sol diyafragma fıtığı içine yerleşmiş olduğunu gösterdi. Acil laparotomide sol diyaframda 4 cm’lik postero-lateral defekt içine fıtıklaşan kolonun splenik fleksurasının sağlıklı olduğu görüldü. Bu kolon segmenti redükte edildi ve defekt emilemeyen sütürlerle onarıldı. Ameliyat sonrası iyileşme sorunsuzdu. Hasta ameliyattan 10 gün sonra taburcu edildi. İnsanlarda gergedanın neden olduğu yaralanmalar son derece nadirdir. Yaşamı tehdit eden travmatik diyafragma hernisi birkaç yıl ertelenebilir. Tanısı için şüphe indeksinin yüksek düzeyde olması gereklidir. Anahtar sözcükler: Gergedan; rüptüre diyafram; travma; yaralanma. Ulus Travma Acil Cerrahi Derg 2020;26(3):486-488

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CA S E R EP O RT

Torsion of wandering spleen nine years after gastric volvulus: Effect of multiparity? Serkan Karaisli, M.D., Turan Acar, M.D., Nihan Acar, M.D., Erdinç Kamer, M.D., Mehmet Hacıyanlı, M.D. Department of General Surgery, İzmir Katip Çelebi University Atatürk Training and Research Hospital, İzmir-Turkey

ABSTRACT Wandering spleen is a rare condition and has life-threatening complications, such as torsion or infarction. It may be asymptomatic or may present with chronic abdominal pain or intraabdominal mass. Since clinical diagnosis is usually difficult, radiological examinations play a very important role in diagnosis. A 37-year-old multiparous woman was admitted to the emergency room with a complaint of abdominal pain. The patient stated that she underwent an operation due to gastric volvulus nine years ago. Preoperative diagnosis was made by ultrasonography and computed tomography. Splenectomy was performed because of the irreversible infarction. Wandering spleen torsion is a rare clinical condition that may cause an acute abdomen. Computerized tomography is the gold standard for preoperative diagnosis. Gastric volvulus and wandering spleen have similar etiologies. In the literature, the coexistence of these two diseases in adulthood is rarely reported. However, to our knowledge, this case is the first report to describe the emergence of these two pathologies at different times in adulthood. Keywords: Acute abdomen; gastric volvulus; pregnancy; splenectomy; wandering spleen.

INTRODUCTION

CASE REPORT

A wandering spleen is a rare entity, which the spleen is in an unusual position and attached only by its hypermobile vascular pedicle. It mostly develops as a result of the ligamentous laxity or lack of ligaments. It may be asymptomatic; it may also present as a painless abdominal mass, frequent recurrent abdominal pain, pressure-related ileus or torsion-related acute abdomen. The spleen is not located in normal anatomic location, and pelvis is the most common localization.[1] When asymptomatic, there is no need for treatment. Laparoscopic or open splenectomy is recommended in the presence of infarction, while splenopexy is adequate in the absence of ischemia. Herein, we aim to present a case that underwent splenectomy due to torted wandering spleen nine years after gastropexy for gastric volvulus.

A 37-year-old Caucasian female patient (Gravidity 4, Parity 4) was admitted to the emergency room with a complaint of abdominal pain, which had lasted for three days. Her past medical history was unremarkable except for detorsion and anterior abdominal wall fixation procedure due to gastric volvulus nine years ago (Gravidity 1, Parity 1). There was a midline incision scar in the upper abdomen. Physical examination revealed tachycardia, hypotension and axillary body temperature of 38.3 °C. There were severe abdominal tenderness, muscular defense, and a mass was palpated on the suprapubic region. Blood tests were normal except for thrombocytopenia (83.000/mm3), elevated white blood cell count (19200/ mm3) and C-reactive protein (17 mg/dL). Abdominal ultrasonography (US) revealed an enlarged spleen located in the

Cite this article as: Karaisli S, Acar T, Acar N, Kamer E, Hacıyanlı M. Torsion of wandering spleen nine years after gastric volvulus: Effect of multiparity? Ulus Travma Acil Cerrahi Derg 2020;26:489-492. Address for correspondence: Serkan Karaisli, M.D. İzmir Katip Çelebi Üniversitesi Atatürk Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İzmir, Turkey Tel: +90 232 - 243 43 43 E-mail: skaraisli@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):489-492 DOI: 10.14744/tjtes.2019.91606 Submitted: 18.10.2018 Accepted: 02.05.2019 Online: 14.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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(a)

(b)

Figure 1. Axial image of computed tomography. Pelvic huge spleen (S) and torsion of splenic artery and vein (arrow) are seen (a). Torsion of vessels is clearly seen in two regions on the coronal image of computed tomography (arrows). Pelvic spleen (S) has demonstrably lower intravenous contrast enhancement than liver (L) (b).

pelvis. Contrast-enhanced abdominal computed tomography (CT) showed a giant ischemic pelvic spleen due to vascular torsion (Fig. 1a, b).

ple foci of necrosis were seen (Fig. 2). Splenectomy was performed because ischemia did not improve when the spleen was detorsioned. A drain was placed to the Douglas pouch.

The patient was brought to the operating room and placed in a supine position. A midline incision was applied under general anesthesia. In the intraoperative examination, fixation sutures of the previous operation were seen between the stomach and anterior abdominal wall. A huge pelvic spleen with a long splenic pedicle that was twisted two times (720 degrees) was observed. The spleen was ischemic, and multi-

The patient was discharged on the fourth postoperative day without any complication. Postoperative pneumococcal, meningococcal and influenza vaccines were administered two weeks after the operation. The pathological examination confirmed a congestive ischemic spleen. The patient had remained well for a two-year follow-up period. Written informed consent was obtained from the patient who participated in this study.

DISCUSSION Wandering spleen is not a common condition and accounts for less than 0.5 % of all splenectomies. Approximately 500 cases have been described in the literature. Children under 10 years old accounts for a third of all cases. 70–80% of adult patients are women and the risk increases in the age group of 20–40 years.[1] The spleen is fixed in its anatomical position by the gastrosplenic, splenocolic and splenorenal ligaments. The wandering spleen usually migrates into the pelvis due to the effect of gravity. The wandering spleen may occur due to congenital malformations of the ligaments or long splenic pedicle. Some diseases, such as malaria, lymphoma and chronic myeloid leukemia, which cause splenomegaly, are considered as acquired causes. Abdominal wall weakness, hormonal changes in pregnancy and multiple pregnancies are also associated with wandering spleen, which explains both higher incidences among women in childbearing period and hormonal changes during pregnancy leading to ligamentous laxity.[2]

Figure 2. Intraoperative examination of the ischemic spleen.

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abdominal mass with notched surfaces may be palpated, but a clinical diagnosis is usually difficult. It may also be noticed incidentally on radiological scans applied for a different reason. It may present with chronic abdominal pain due to intermittent spontaneous torsion and detorsion attacks. In a patient with torsion, signs of peritoneal irritation, such as severe abdominal pain, fever, nausea, vomiting, may occur.[2] Additionally, obstructive uropathy, gastric/duodenal/ colonic obstruction and portal hypertension due to the pressure to the adjacent organs may develop. Almost the whole described wandering spleen cases in the literature underwent surgery due to they presented with an acute abdomen. We did not see any reports about long-term follow-up results of asymptomatic patients or who applied conservative surgery. That is why we believe that this rare entity is not considered to be important for clinicians until patients need urgent surgery. Laboratory findings are nonspecific. Thrombocytopenia and leukocytosis can be detected, such as in our case. The diagnosis is confirmed by radiological examination. Grayscale and Doppler US are effective, cheap, easy and noninvasive methods to detect wandering spleen and torsion. Additionally, Doppler US shows the presence or absence of splenic vascular flow. CT is gold standard for diagnosis. CT shows a whorled appearance, which is a pathognomonic sign of torsion of the splenic pedicle.[3] The enlarged spleen due to venous blockage may be seen. Minimal or absent contrast enhancement of the spleen, which is considered to be an indicator of infarction, may be detected.[3,4] On non-contrast sections, the spleen shows lower density values in comparison with the hepatic parenchyma and hyperdensity of the splenic pedicle may be a sign of the thrombosed vein.[3] MRI can be preferred as an alternative to CT. Our patient had typical US and CT findings of wandering spleen with complete infarction. The preoperative findings were verified during the intraoperative examination and following pathological examination. The treatment is surgery. Laparoscopic or open interventions may be performed. The type of surgical procedure is chosen according to the viability of the spleen. If torsion is absent or blood circulation of the detorsioned spleen is normal, splenopexy is recommended. However, if the spleen is ischemic due to thrombosis of splenic artery or vein, splenectomy should be performed.[2]. Since our patient had an ischemic spleen, we performed splenectomy. Gastric volvulus is another rare entity and shares a common etiology with wandering spleen. The coexistence of these two diseases has been described only four times in adults. [5–8] Those cases were reported to have both pathologies at the time of diagnosis. Omata et al.[5] and Lianos et al.[7] made a diagnosis of wandering spleen during surgical intervention, while other authors[6,8] detected it on CT scan preoperatively applied. All authors[5–7] except for one[8] performed gastropexy without splenopexy or splenectomy. Splenic torsion to be constrained splenectomy was not noted in those case Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3

reports, and the authors advocated gastric fixation would prevent splenic hypermobility. Authors reported that no relapse or complication was experienced in patients who underwent only gastropexy during a mean of 13-month follow-up.[5,7] In the presented case, there were nine years between the occurrences of these two diseases. No evidence was found about wandering spleen or hiatal hernia when a detailed previous operation note was checked. It was understood that the wandering spleen developed in the later years after the gastropexy procedure. It was learned that gastropexy was administrated to our patient, such as reported cases. Although authors[5,7] presented that no relapse or complication was experienced during their short time follow-up, wandering spleen occurred nine years after gastropexy in our case. That is why long term follow-up should be considered in patients who underwent gastropexy. Additionally, this report is important to show that gastropexy without splenopexy is not adequate to block hypermobility of spleen contrary to what is believed. On the other hand, the patient had a medical history of single pregnancy at the time of the first operation. Torted wandering spleen was observed after three pregnancies, which in nine years. When considered from this point of view, it appears that these pathologies which have a common etiology may not always coexist. We believe that pregnancy and birth processes may increase the risk of wandering spleen in patients with a history of gastric volvulus. The wandering spleen should be kept in mind in the differential diagnosis of the abdominal mass. Torsion of the pedicle may cause an acute abdomen. In the presence of infarction, open or laparoscopic splenectomy should be planned. Patients with a history of gastric volvulus should be evaluated carefully for wandering spleen, which is another possible result of ligamentous laxity. In addition, we think that being multipara may increase the risk of wandering spleen years after gastropexy operation. Surgeons should be aware of this potential risk for women patients in reproductive age, and long-term follow-up should be considered.

Acknowledgements We thank all general surgery department staff for their cooperation. This case report was not supported by any company. None of the authors has financial or proprietary interests in any material mentioned. 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: T.A., N.A.; Design: S.K., T.A.; Supervision: E.K., M.H.; Fundings: N.A., E.K.; Materials: S.K., T.A.; Data: T.A., E.K.; Analysis: S.K., N.A., M.H.; Literature search: S.K., T.A.; Writing: S.K., N.A.; Critical revision: E.K., M.H. 491


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Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Buehner M, Baker MS. The wandering spleen. Surg Gynecol Obstet 1992;175:373–87. 2. Yakan S, Telciler KE, Denecli AG. Acute torsion of a wandering spleen causing acute abdomen. Hong Kong J Emerg Med 2011;18:34–6. 3. Chu J, Li Z, Luo B, Yang J. Wandering spleen with torsion and complete infarction. Acta Radiol 2011;52:911–3. 4. Ghahremani S, Sabour M, Ghahremani S, Bazrafshan A, Sadeghi R. A wandering spleen detected by 99mTc-denatured RBC scan. Iran J Nucl

Med 2018;26:66−7. 5. Omata J, Utsunomiya K, Kajiwara Y, Takahata R, Miyasaka N, Sugasawa H, et al. Acute gastric volvulus associated with wandering spleen in an adult treated laparoscopically after endoscopic reduction: a case report. Surg Case Rep 2016;2:47. 6. Matsushima K, Kayo M, Hachiman H, Gushimiyagi M. Laparoscopic repair of gastric volvulus associated with wandering spleen in an adult: report of a case. Surg Today 2006;36:843–5. 7. Lianos G, Vlachos K, Papakonstantinou N, Katsios C, Baltogiannis G, Godevenos D. Gastric volvulus and wandering spleen: a rare surgical emergency. Case Rep Surg 2013;2013:561752 8. Ooka M, Kohda E, Iizuka Y, Nagamoto M, Ishii T, Saida Y, et al. Wandering spleen with gastric volvulus and intestinal non-rotation in an adult male patient. Acta Radiol Short Rep 2013;2:2047981613499755.

OLGU SUNUMU - ÖZET

Gastrik volvulustan dokuz yıl sonra görülen gezici dalak torsiyonu: Multiparitenin etkisi? Dr. Serkan Karaisli, Dr. Turan Acar, Dr. Nihan Acar, Dr. Erdinç Kamer, Dr. Mehmet Hacıyanlı İzmir Katip Çelebi Üniversitesi Atatürk Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, İzmir

Gezici dalak nadir görülen bir durumdur ve torsiyon veya enfarktüs gibi hayatı tehdit eden komplikasyonlara sebep olabilir. Semptomsuz olabilir, kronik abdominal ağrı veya intraabdominal kitle ile prezente olabilir. Klinik tanısı genellikle zor olduğu için, radyolojik incelemeler tanıda çok önemli bir rol oynamaktadır. Otuz yedi yaşında multipar kadın karın ağrısı şikayeti ile acil servise başvurdu. Hastanın öyküsünden dokuz yıl önce gastrik volvulus nedeniyle ameliyat geçirdiğini öğrenildi. Ameliyat öncesi tanı ultrasonografi ve bilgisayarlı tomografi ile yapıldı. İrreversibl infarkt nedeniyle splenektomi yapıldı. Gezici dalak torsiyonu, akut karına neden olabilen nadir bir klinik durumdur. Bilgisayarlı tomografi ameliyat öncesi tanı için altın standarttır. Gastrik volvulus ve gezici dalak benzer etiyolojilere sahiptir. Literatürde, bu iki hastalığın yetişkinlikte birlikteliği nadiren bildirilmiştir. Bununla birlikte, bildiğimiz kadarıyla, bu olgu, yetişkinlikte farklı zamanlarda bu iki patolojinin ortaya çıkışını bildiren ilk çalışmadır. Anahtar sözcükler: akut karın, gastrik volvulus. gebelik, gezici dalak, splenektomi Ulus Travma Acil Cerrahi Derg 2020;26(3):489-492

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A rare case: Isolated superior mesenteric vein injury occurring after blunt abdominal trauma Mehmet Kubat, M.D. Department of General Surgery, Alaaddin Keykubat University Alanya Training and Research Hospital, Antalya-Turkey

ABSTRACT Intraabdominal vascular injuries due to blunt abdominal trauma are rare. It is very difficult to visualize superior mesenteric vein (SMV) and portal vein injuries under emergency conditions. In this case study, we reported a low-speed car accident, a patient with isolated SMV injury as a result of a blunt abdominal trauma that arose from a collision with a steering wheel. A 62-year-old male patient was admitted to the emergency department with minimal distention and diffuse tenderness in the abdomen. The presence of diffuse fluid in the abdomen and suspected liver injury were reported in ultrasonography. The presence of fluid in perihepatic and perisplenic areas was detected in abdominal tomography. No solid organ injury was observed. Laparotomy revealed an injury in the small intestine mesentery. There was a defect on SMV under splenic vein combination. End side vein anastomosis and primary repair were performed. During six months follow-up, the patient did not have active complaints, and there was no pathology in the SMV and portal vein. We think that the use of vascular repair techniques applied by experienced surgeons in hemodynamically stable superior mesenteric venous injuries is important concerning continuity of anatomical and functional integrity. Keywords: Blunt abdominal trauma; injury; superior mesenteric vein.

INTRODUCTION Blunt and penetrating abdominal traumas affect primarily solitary and hollow organs. Abdominal vascular injuries are associated with high mortality and morbidity and often arise from penetrating traumas. Intraabdominal vascular injuries that arise from blunt abdominal trauma are rare, and blunt abdominal traumas resulting in an isolated superior mesenteric vein (SMV) injuries are extremely rare.[1] Visualizations of the superior mesenteric vein and the portal vein are extremely difficult in emergency situations, and the difficulty in isolating injured vessels and the presence of other accompanying major abdominal injuries result in increased mortality and morbidity.[2] The ligation of the relevant vessel is one option in cases with unstable hemodynamic status, although the method is associated with congestive complications.[3,4] This case report presents a patient who sustained a

blunt abdominal trauma from a steering wheel during a lowvelocity road traffic accident and relays our approach to the treatment.

CASE REPORT A 62-year-old male patient was admitted to the emergency room after sustaining a blunt abdominal trauma during a road traffic accident. In an examination of the accident records, it was realized that the accident occurred at a velocity of 20 km/h and that the patient’s abdomen hit the steering wheel, as he was not restrained by a seat belt. The patient’s medical history was unremarkable, other than hypertension. An initial physical examination upon arrival to the emergency room revealed a Glasgow Coma Scale score of 15; blood pressure 130/90 mmHg; pulse 92 bpm; and SpO2 97 percent. A physical examination revealed minimal abdominal

Cite this article as: Kubat M. A rare case: Isolated superior mesenteric vein injury occurring after blunt abdominal trauma. Ulus Travma Acil Cerrahi Derg 2020;26:493-495. Address for correspondence: Mehmet Kubat, M.D. Alaaddin Keykubat Üniversitesi Alanya Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, Antalya, Turkey Tel: +90 242 - 513 48 41 E-mail: dr.m.kubat@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(3):4963-495 DOI: 10.14744/tjtes.2019.39932 Submitted: 17.02.2019 Accepted: 17.06.2019 Online: 13.05.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Kubat. A rare case: Isolated SMV injury occurring after blunt abdominal trauma

distension and diffuse tenderness, while other system examinations uncovered no other additional pathological findings. Hemoglobin was 15 g/dl, and hematocrit was 44.3 percent. An emergency abdominal ultrasonography revealed the presence of extensive intraabdominal fluid and suspected liver injury, and a subsequent abdominal computed tomography detected perihepatic and perisplenic fluid that was possibly hemorrhagic in nature (Fig.1). There was no evidence of solid organ injury, and thoracic and pelvic CT scans revealed no pathology. Immediate fluid resuscitation was initiated with a 1,000 ml crystalloid solution, and a laparotomy was performed at one hour after admission to the emergency room. Blood pressure was 90/60 mmHg and the pulse rate was 110 bpm. An exploration revealed approximately 3,000 ml of intraabdominal hemorrhagic fluid, but no solid or hollow organ injury. A 6-cm injury was identified at the base of the small bowel mesentery, inferior to the transverse colon mesentery, with a surrounding hematoma, and also active venous bleeding. The bleeding site was packed, and the injured site was dissected. An approximately 15 mm avulsion tear and defect were found above the SMV and below the confluence of the splenic vein that was considered to be secondary to traction by collateral vessels.

Figure 1. Abdominal tomography wiew of the patient. Presence of fluid in perihepatic and perisplenic areas.

Figure 2. Intraoperative photo of the end-to-side vascular anastomosis.

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An end-to-side vascular anastomosis was performed with a 5/0 prolene suture, and the defect was primarily repaired (Fig. 2). The patient received three units of erythrocyte suspension, and approximately 4,000 ml colloid volume expanders and crystalloid fluid replacement during surgery. The patient was followed up in the intensive care unit for two days after surgery, and oral intake was initiated after two days. SMV and portal venous flows were followed with CT angiography and Doppler ultrasonography. After confirming that no additional pathology existed in the gastrointestinal tract of the patient and that all functions were normal, the patient was discharged on day 12 following surgery with appropriate anticoagulation therapy. During the 6-month follow-up period, the patient reported no active complaints and investigations showed no pathology in the SMV and portal vein. The follow-up program was ceased in accordance with the desire of the patient. Patient’s consent was obtained for this study.

DISCUSSION Isolated superior mesenteric vein (SMV) injuries that arise from blunt abdominal traumas have only rarely been reported. Intraabdominal vascular injuries are often accompanied by other solid and hollow organ injuries.[5] Killen et al.[6] reported a 0.2 percent incidence rate for mesenteric vein injury caused by blunt abdominal trauma. Abdominal vascular injuries mostly arise from penetrating injuries and abdominal vascular injuries secondary to blunt abdominal trauma mostly arise from traffic accidents.[7] Mesenteric vascular injuries due to blunt abdominal trauma often occur as a result of opposing forces exerted by the mesentery itself against its fixed point. In a study of 302 patients with abdominal vascular injuries reported by Ansesio et al.,[1] SMV was the second most commonly affected vein (n=33, 13%) and 19 patients had isolated SMV injuries. The rate of mortality associated with isolated injuries was 52.7 percent, while in another study, a mortality rate of 45 percent was reported associated with isolated superior mesenteric vein injury.[4] There is a lack of consensus on the treatment options in SMV injuries, and at least five treatment methods have been described as follows: ligation, lateral repair, endto-end anastomosis, and autologous and prosthetic grafting. A simple ligation must be preferred in patients with unstable or multiple injuries due to venous congestion and similar complications.[5,7] Collaterals that will develop with retroperitoneal Retzius veins are important in this approach, and this allows faster hemodynamic stability. Donahue and Strauch[8] found that patients undergoing ligation had higher survival rates (85%) than those undergoing venography (64%). The selection of vessel repair methods in mesenteric vein injuries would be more appropriate concerning anatomic and functional considerations, although these methods come with technical difficulties. Kostka et al.[9] reported on a patient who was treated with end-to-end anastomosis and who suffered no additional problems in the follow-up period. In the same Ulus Travma Acil Cerrahi Derg, May 2020, Vol. 26, No. 3


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patient, the gastrointestinal passage returned to normal at postoperative day 9, and the patient was discharged on day 20. The patient in the present was started on the oral intake of liquid food at postoperative day 2 and was discharged on postoperative day 12. Miyauchi et al.[3] stated that three weeks should elapse following ligation for the development of collateral vessels and the regression of congestion and edema in the small bowel. Tulip et al.[10] reported on a patient who developed overwhelming small bowel edema with the formation of thrombosis in the collateral vessels and SMV following vessel ligation, and carried out bypass surgery between the SMV and splenic vein using the autologous femoral vein. Ball et al.[11] performed a vessel ligation on a female patient with an SMV injury who was hemodynamically unstable and had to perform saphenous vein graft due to the identification of small bowel ischemia on a control laparotomy. It is apparent that the functions of the gastrointestinal tract following vessel ligation return to normal over a long period, and may even lead to ischemia. On the other hand, Coimbra et al.[5] reported on a patient who developed thrombosis and extensive small bowel necrosis following SMV resection and end-to-end anastomosis. Although no such similar situation was noted in the present patient, we were well aware that such complications could not be ruled out.

Conclusion Despite their rare occurrence, superior mesenteric venous injuries that arise from blunt abdominal traumas are associated with high mortality due to the challenges faced in diagnosis and the isolation of the injured structures. Although ligation is preferable in hemodynamically unstable patients, the long time needed for the development of collateral vessels and the development of small bowel congestions and edema is important drawbacks. The author considers the use of vascular repair techniques performed by experienced surgeons on hemodynamically stable patients to be important for the maintenance of anatomical and functional integrity.

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. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Asensio JA, Chahwan S, Hanpeter D, Demetriades D, Forno W, Gambaro E, et al. Operative management and outcome of 302 abdominal vascular injuries. Am J Surg 2000;180:528-33; discussion 533−4. 2. Fraga GP, Bansal V, Fortlage D, Coimbra R. A 20-year experience with portal and superior mesenteric venous injuries: has anything changed?. Eur J Vasc Endovasc Surg 2009;37:87–91. 3. Miyauchi M, Kushimoto S, Kawai M, Yokota H. Postoperative course after simple ligation for superior mesenteric vein injury caused by blunt abdominal trauma: report of a case. J Nippon Med Sch 2011;78:116–9. 4. Asensio JA, Petrone P, Garcia-Nuñez L, Healy M, Martin M, Kuncir E. Superior mesenteric venous injuries: to ligate or to repair remains the question. J Trauma 2007;62:668–75. 5. Coimbra R, Filho AR, Nesser RA, Rasslan S. Outcome from traumatic injury of the portal and superior mesenteric veins. Vasc Endovascular Surg 2004;38:249–55. 6. Killen DA. Injury of the Superior Mesenteric Vessels Secondary to Nonpenetrating Abdominal Trauma. Am Surg 1964;30:306–12. 7. Courcy PA, Brotman S, Oster-Granite ML, Soderstrom CA, Siegel JH, Cowley RA. Superior mesenteric artery and vein injuries from blunt abdominal trauma. J Trauma 1984;24:843–5. 8. Donahue TK, Strauch GO. Ligation as definitive management of injury to the superior mesenteric vein. J Trauma 1988;28:541–3. 9. Kostka R, Sojáková M. Isolated superior mesenteric vein injury from blunt abdominal trauma: report of a case. Surgery today 2006;36:190−2. 10. Tulip HH, Smith SV, Valentine RJ. Delayed reconstruction of the superior mesenteric vein with autogenous femoral vein. J Vasc Surg 2012;55:1773–4. 11. Ball CG, Kirkpatrick AW, Smith M, Mulloy RH, Tse L, Anderson IB. Traumatic Injury of the Superior Mesenteric Vein: Ligate, Repair or Shunt?. Eur J Trauma Emerg Surg 2007;33:550–2.

OLGU SUNUMU - ÖZET

Nadir bir olgu: Künt abdominal yaralanma sonucu gelişen izole süperiyor mezenterik ven yaralanması Dr. Mehmet Kubat Alaaddin Keykubat Üniversitesi Alanya Eğitim ve Araştırma Hastanesi, Genel Cerrahi Anabilim Dalı, Antalya

Künt karın travmalarına bağlı intraabdominal vasküler yaralanmalara ender rastlanmaktadır. Süperiyor mezenterik ven (SMV) ve portal ven yaralanmalarının acil şartlarda görüntülenmesi oldukça zordur. Bu yazıda, düşük hızlı araç içi trafik kazasında direksiyon simidine çarpma ile oluşan künt batın travması sonucu izole SMV yaralanması olan hasta ve tedavi yaklaşımımız sunuldu. Altmış iki yaş erkek hasta acil servise girişini takiben yapılan muayenesinde karında minimal distansiyon ve yaygın hassasiyet olduğu görüldü. Ultrasonografisinde, karın içerisinde yaygın mayi varlığı ve şüpheli karaciğer yaralanması bildirildi. Abdominal tomografide perihepatik ve perisplenik alanlarda sıvı varlığı saptandı. Solid organ yaralanmasının olmadığı görüldü. Laparatomide ince bağırsak mezenterinde yaralanma görüldü. SMV üzerinde splenik ven birleşimi altında defekti mevcuttu. Uç yan damar anastomozu ve primer onarım gerçekleştirildi. Altı ay süreyle yapılan takiplerinde hastanın aktif şikâyeti olmadığı, yapılan tetkikler sonucunda SMV ve portal ven de patoloji olmadığı görüldü. Hemodinamik açıdan stabil olan süperior mezenterik venöz yaralanmalarında tecrübeli cerrahlarca uygulanan vasküler onarım tekniklerinin kullanılmasının anatomik ve fonksiyonel bütünlüğün devamlılığı açısından önemli olduğunu düşünmekteyiz. Anahtar sözcükler: Künt abdominal travma; süperiyor mezenterik ven; yaralanma. Ulus Travma Acil Cerrahi Derg 2020;26(3):493-495

doi: 10.14744/tjtes.2019.39932

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