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RESPI RATORY

CASEREPORTS Ci l t / Vol ume6 S a y ı / I s s ue: 2 Yı l / Yea r : 2017

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Respir Case Rep 2017;6(2):74-77 DOI: 10.5505/respircase.2017.35220

OLGU SUNUMU

CASE REPORT

Advanced Primary Pulmonary Carcinosarcoma: A Case Report and Review of the Literature İlerlemiş Primer Pulmoner Karsinosarkom: Olgu sunumu ve Literatürün Gözden Geçirilmesi

RESPIRATORY CASE REPORTS

Iliass Elalami1, Rachid Tanz1, Mohamed Amine Azami2, Mohamed Allaoui2, Hassan Errihani3, Mohamed Ichou1

Abstract

Özet

Pulmonary carcinosarcoma (PCS) is a rare tumor, that comprises approximately 0.2% to 0.4% of all pulmonary neoplasms. PCS was defined in the World Health Organization classification as "poorly differentiated non-small cell lung carcinomas containing a sarcoma-like element or sarcomatous component". Presently, described is case of a 46-year-old male who presented with advanced primary PCS.

Pulmoner karsinosarkom nadir bir tümör olup tüm pulmoner maligniteler içerisinde yaklaşık %0,2 ile %0,4 arasında görülmektedir. Pulmoner karsinosarkom Dünya Sağlık Örgütü sınıflamasında “sarkom benzeri element veya sarkomatöz komponent içeren az differansiye küçük hücreli dışı akciğer kanseri” olarak tanımlanmıştır. İleri evre primer pulmoner karsinosarkom saptanan 46 yaşındaki erkek olguyu sunuyoruz.

Key words: Pulmonary carcinosarcoma, sarcomatoid carcinoma, chemotherapy.

Carcinosarcoma (CSA) of the lung is a rare malignant tumor. It was first defined by Kika et al. (1) in 1908 as poorly differentiated non-small cell carcinoma containing a component with sarcoma or sarcoma-like features. It is estimated to account for only 0.2% to 0.4% of all pulmonary neoplasms (2). There are strong associations with smoking and 1

Department of Medical Oncology, Military Hospital Med V Faculty of Medicine, Mohamed V University, Rabat, Morocco 2 Department of Pathology, Military Hospital Med V Faculty of Medicine, Mohamed V University, Rabat, Morocco 3 Department of Medical Oncology, National Institute of Oncology, Rabat, Morocco

Anahtar Sözcükler: Pulmoner karsinosarkom, sarkomatoid karsinoma, kemoterapi.

asbestosis. Clinical characteristics, preoperative diagnostic methods, and prognostic factors are still not completely understood (3). Prognosis is poor; 2-year survival after surgical resection is not greater than 10% (4). Described is a new case of patient with advanced primary PCS. 1

Mohamed V Üniversitesi, Tıp Fakültesi Askeri Hastanesi, Tıbbi Onkoloji Anabilim Dalı, Rabat, Fas 2 Mohamed V Üniversitesi, Tıp Fakültesi Askeri Hastanesi, Patoloji Anabilim Dalı, Rabat, Fas 3 Ulusal Onkoloji Enstitüsü, Tıbbi Onkoloji Anabilim Dalı, Rabat, Fas

Submitted (Başvuru tarihi): 04.07.2016 Accepted (Kabul tarihi): 15.11.2016 Correspondence (İletişim): Rachid Tanz, Department of Medical Oncology, Military Hospital Med V Faculty of Medicine, Mohamed V University, Rabat, Morocco e-mail: tanz.rachid@gmail.com

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Respiratory Case Reports

CASE A 46-year-old man with history of 25 years of smoking complained of chest pain, cough, hemoptysis, and weight loss. Physical examination was normal. Chest X-ray revealed heterogeneous mass in the right pulmonary lobe. Chest computerized tomography (CT) revealed large mass measuring 11 x 10 cm extending to the pleural and thoracic spine (Figure 1).

direct mechanism between toxicity of asbestos and emergence of sarcomatoid component (6,7) Clinical presentation of central localization-type involves cough, dyspnea, and hemoptysis, like other endobronchial tumors. The second type of PCS, peripheral, solid, parenchymal-type, often presents as large mass. These tumors are asymptomatic in the early stage, during which time they may involve adjacent organs or structures, such as the mediastinum, pleura, and thoracic wall (8). In our patient, dyspnea and cough were first symptoms to appear, followed by rapid deterioration of physical condition.

Figure 1: Chest computed tomography scan indicating right pulmonary mass

Transparietal biopsy was performed. Microscopic examination of biopsy specimen revealed infiltrating neoplasm with biphasic pattern (epithelial and sarcomatous components). Epithelial component was made up of massive cells of undifferentiated carcinoma with high cytonuclear atypia. Sarcomatous component was made up of spindle cells with hyperchromatic nuclei, arranged in bundles. Immunohistochemical study revealed that epithelial component expressed cytokeratin antigen (AE1/AE3), while sarcomatous component expressed vimentin antigen and thyroid transcription factor 1 (Figure 2). According to these findings, final diagnosis of PCS was made. CT of the head was normal; bone scan revealed multiple bone metastases. Pathological stage was therefore stage IV. Surgery and radiotherapy were challenged and palliative chemotherapy was recommended with docetaxel (75 mg/m2) and cisplatin (80 mg/m2) for 3 cycles. The patient died within 4-month follow-up period.

DISCUSSION PCS is a rare tumor that comprises approximately 0.2% to 0.4% of all pulmonary neoplasms (2). The literature reports 4 to 7.25-fold male (5). Mean age at diagnosis is between 65 and 75 years. Some cases have been reported related to asbestos exposure. In a study conducted by Fishback (3), 3% of patients with sarcomatoid carcinoma (SC) were exposed to asbestos. Thus, there could be Cilt - Vol. 6 SayÄą - No. 2

Figure 2a, b, c and d: A) Pulmonary parenchyma revealing infiltration of biphasic malignant tumor (hematoxylin and eosin; magnification x200); B) Pancytokeratin expression in the epithelial component; C) Vimentin immunohistochemical stain positive in the mesenchymal component; D) Epithelial pattern expressing thyroid transcription factor

Radiologically, SC is usually a single lesion with large diameter (from 40 to 180 mm) and central or peripheral location in the upper lobes. Tumor is usually locally advanced at time of diagnosis, with large proportion of pleural invasion, either visceral or parietal (40-70% of cases) (7,9). Present patient had large tumors (118 and 95 mm, respectively) with parietal invasion. PCS is defined in the World Health Organization classification as "poorly differentiated non-small cell lung carcinoma (NSCLC) containing sarcoma-like element (malignant spindle or giant cells) or sarcomatous component (9). Five types of carcinoma have been defined, based on specific histological criteria: giant cell carcinoma, pleomorphic carcinoma, CSA, spindle cell carcinoma, and pulmonary blastoma. Although CSA is generally difficult to diagnose preoperatively due to mixed composition of both epithelial and sarcomatous components, several reports have described preoperative diagnosis at approximate rate of 0% to 12% (7,10). Macroscopically, CSA is

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Advanced Primary Pulmonary Carcinosarcoma: A Case Report and Review of the Literature | Tanz et al.

usually gray-white in color, with hemorrhagic and/or necrotic areas (11,12). CSA is a malignant tumor that consists of mixture of NSCLC (typically squamous cell carcinoma in [40-70%] or adenocarcinoma) and sarcoma-containing heterologous elements, such as rhabdomyosarcoma, chondrosarcoma, and osteosarcoma. Immunohistochemistry can prove epithelial nature of proliferation of predominantly fusiform or giant cells based on positivity of pancytokeratins. Pancytokeratin AE1/AE3 appears to be most sensitive in recognizing epithelial component (13). Other epithelial markers, such as epithelial membrane antigen, CAM5.2 (including pancytokeratin CK 18) or p63/p40, may help in identification of epithelial component. However, vimentin is not a specific marker of mesenchymal tumor because many carcinomas express and especially bronchopulmonary adenocarcinoma. Some markers, such as actin, desmin, myoglobin, and S100 protein, also help to better characterize sarcomatoid contingent of CSA (14). CSA is a clonal tumor developing via sarcomatoid change in a carcinoma. TP53 mutations are often present in CSA, whereas KRAS mutations occur less frequently, and EGFR mutations are very uncommon (15). Programmed death-1 (PD-1) is a co-inhibitory inducible receptor present on T-cells and macrophages. Tumor cells with increased programmed death ligand-1 (PD-L1) are believed to escape immunity through activation of PD-1/PD-L1 pathway and suppression of effector immune responses. Recent strategies targeting PD-1/PD-L1 axis have shown promising results in patients with several tumor types, including lung carcinomas. Expression of PD-L1 in 13 SCs from 2 large retrospective lung cancer cohorts showed that 9 of 13 (69.2%) patients with SCs were positive for PD-L1, and level was higher than in conventional NSCLC. These results provide rationale for potential use of targeted immunotherapy in lung SC (16). For localized tumors, complete surgical removal of tumor with negative tumor margins constitutes desired treatment approach. In addition to surgical resection, radiation is well established and effective as standard therapy in combination with surgery. Even if the sarcoma is resected incompletely and resection margins show residual tumor on microscopy, rate of local recurrence can be reduced to about 15% with local radiation therapy (17). However, there is limited information on systemic treatment options, such as chemotherapy and radiotherapy, for metastatic disease (18,19).

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There are few reports discussing chemotherapy for CSA due to rarity of this entity. Two reports have demonstrated efficacy of doxorubicin-based chemotherapeutic regimen and combination of cisplatin and doxorubicin (19). Aggressive nature and poor differentiation of this tumor render treatment difficult and result in poor prognosis (20).

ABBREVIATIONS PCS: Pulmonary carcinosarcoma; NSCLCs: non-small cell lung carcinomas; WHO: World Health Organization; CSA: Carcinosarcoma; CT: computerized tomography; TTF1: thyroid transcription factor

CONFLICTS OF INTEREST None declared.

AUTHOR CONTRIBUTIONS Concept - I.E., R.T., M.A.A., M.A., H.E., M.I.; Planning and Design - I.E., R.T., M.A.A., M.A., H.E., M.I.; Supervision - I.E., R.T., M.A.A., M.A., H.E., M.I.; Funding -; Materials -; Data Collection and/or Processing -; Analysis and/or Interpretation -; Literature Review -; Writing -; Critical Review -

YAZAR KATKILARI Fikir - I.E., R.T., M.A.A., M.A., H.E., M.I.; Tasarım ve Dizayn - I.E., R.T., M.A.A., M.A., H.E., M.I.; Denetleme I.E., R.T., M.A.A., M.A., H.E., M.I.; Kaynaklar -; Malzemeler -; Veri Toplama ve/veya İşleme -; Analiz ve/veya Yorum -; Literatür Taraması -; Yazıyı Yazan -; Eleştirel İnceleme -

REFERENCES 1.

Kakos GS, Williams Jr TE, Assor D, Vasko JS. Pulmonary carcinosarcoma. Etiologic, therapeutic, and prognostic considerations. J Thorac Cardiovasc Surg 1971; 61:777-83.

2.

Sato S, Koike T, Yamato Y, Yoshiya K, Motono N, Takeshige M, et al. A case of rapidly growing pulmonary carcinosarcoma. Int J Clin Oncol 2010; 15:319-24. [CrossRef]

3.

Fishback NF, Travis WD, Moran CA, Guinee DG Jr, McCarthy WF, Koss MN. Pleomorphic (spindle/giant cell) carcinoma of the lung: a clinicopathologic correlation of 78 cases. Cancer 1994; 73:2936-45. [CrossRef]

www.respircase.com


Respiratory Case Reports

4.

Martin LW, Correa AM, Ordonez NG, Roth JA, Swisher SG, Vaporciyan AA, et al. Sarcomatoid carcinoma of the lung: a predictor of poor prognosis. Ann Thorac Surg 2007; 84:973-80. [CrossRef]

5.

Nakajima M1, Kasai T, Hashimoto H, Iwata Y, Manabe H. Sarcomatoid carcinoma of the lung: a clinicopathologic study of 37 cases. Cancer 1999; 86:608-16. [CrossRef]

6.

Ishida T, Tateishi M, Kaneko S, Yano T, Mitsudomi T, Sugimachi K, et al. Carcinosarcoma and spindle cell carcinoma of the lung. Clinicopathologic and immunohistochemical studies. J Thorac Cardiovasc Surg 1990; 100:844-52.

7.

Davis MP, Eagan RT, Weiland LH, Pairolero PC. Carcinosarcoma of the lung: Mayo Clinic experience and response to chemotherapy. Mayo Clin Proc 1984; 59:598603. [CrossRef]

8.

Humphrey PA1, Scroggs MW, Roggli VL, Shelburne JD. Pulmonary carcinomas with a sarcomatoid element: an immunocytochemical and ultrastructural analysis. Hum Pathol 1988; 19:155-65. [CrossRef]

9.

Travis WD, Brambilla E, Müller-Hermelink K, Harris C, Kleihues C, Sobin P. Pathology and genetics of tumors of the lung, pleura, thymus, and heart. World Health Organization Classification of Tumours. Lyon: IARC Press; 2004. p. 53-58. http://www.iarc.fr/en/publications/pdfsonline/pat-gen/bb10/BB10

10. Huwer H, Kalweit G, Straub U, Feindt P, Volkmer I, Gams E. Pulmonary carcinosarcoma: diagnostic problems and determinants of the prognosis. Eur J Cardiothorac Surg 1996; 10:403–7. [CrossRef] 11. Kim KI, Flint JD, Müller NL. Pulmonary carcinosarcoma: radiologic and pathologic findings in three patients. AJR Am J Roentgenol 1997; 169:691–4. [CrossRef]

13. Travis WD. Sarcomatoid neoplasms of the lung and pleura. Arch Pathol Lab Med 2010; 134:1645-58. [CrossRef] 14. Vieira T, Antoine M, Ruppert AM, Fallet V, Duruisseaux M, Giroux Leprieur E, et al. Blood vessel invasion is a major feature and a factor of poor prognosis in sarcomatoid carcinoma of the lung. Lung Cancer 2014; 85:276-81. [CrossRef] 15. Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JH, Beasley MB, et al. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol. 2015;10: 1243-60. [CrossRef] 16. Velcheti V, Rimm DL, Schalper KA. Sarcomatoid lung carcinomas show high levels of programmed death ligand-1 (PD-L1); J Thorac Oncol 2013; 8: 803–5. [CrossRef] 17. Braham E, Ben Rejeb H, Aouadi S, Kilani T, El Mezni F. Pulmonary carcinosarcoma with heterologous component: report of two cases with literature review. Ann Transl Med 2014; 2:41. [CrossRef] 18. Sugano T, Mori M, Namba Y, Uenami T, Kagami S, Yokota S. A case of sarcomatoid carcinoma of the lung successfully treated with carboplatin, paclitaxel and bevacizumab. Nihon Kokyuki Gakkai Zasshi 2011; 49:304-8. 19. Langer F, Wintzer HO, Werner M, Weber C, Brümmendorf TH, Bokemeyer C. A case of pulmonary carcinosarcoma (squamous cell carcinoma and osteosarcoma) treated with cisplatin and doxorubicin. Anticancer Res 2006; 26:3893-7. 20. Pelosi G1, Sonzogni A, De Pas T, Galetta D, Veronesi G, Spaggiari L, et al., Pulmonary sarcomatoid carcinomas: a practical overview Int J Surg Pathol 2010; 18:103-20. [CrossRef]

12. Koss MN, Hochholzer L, Frommelt RA. Carcinosarcomas of the lung: a clinicopathologic study of 66 patients. Am J Surg Pathol 1999; 23:1514–26. [CrossRef]

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Respir Case Rep 2017;6(2):78-81 DOI: 10.5505/respircase.2017.49389

OLGU SUNUMU

CASE REPORT

An Unusual Cause of Dyspnea and Hoarseness: A Recurrent Respiratory Papillomatosis Nefes Darlığı ve Ses Kısıklığının Ender bir Nedeni: Tekrarlayıcı Respiratuar Papillomatozis

RESPIRATORY CASE REPORTS

Mehmet Akif Özgül1, Erdoğan Çetinkaya1, Mustafa Çörtük2, Derya Özden Omaygenç3

Abstract

Özet

Recurrent respiratory papillomatosis is a rare respiratory condition associated with human papillomavirus. It is characterized by exophytic, wart-like, squamous lesions within the respiratory tract. Presently described is case of a 24-year-old Caucasian male who presented with recurrent laryngotracheal papillomatosis. Laryngoscopy and excisional biopsy had been performed at approximately 1½ years of age. Biopsy specimen was determined to be squamous cell papilloma. The patient received interferon alpha-2a and inhaled interferon, but treatment was discontinued due to lack of regression or delay in reappearance of symptoms. Rigid bronchoscopy has been performed for recurrent papilloma excision approximately every 3 to 4 months for 3 years.

Rekküren respiratuar papillomatozis Human Papilloma Virus'ün neden olduğu nadir bir hastalıktır. Hastalık solunum yollarında siğil benzeri squamoz lezyonlarla karakterizedir. Sunduğumuz olgu 24 yaşında kafkas ırkından bir erkek olup rekküren trakeobronşial papillomatozis saptanmıştır. Olguya 1,5 yaşında iken laringoskopi yapılmış ve lezyon eksize edilerek tanı konulmuştur. Biyopsi materyali squamoz hücreli papilloma olarak raporlanmıştır. Olgu daha önce interferon α-2a ve inhaler interferon tedavisi almış fakat semptomlarda duraklama veya gerileme olmaması nedeniyle sonlandırılmıştı. Hastaya 3 yıldır her 3 ile 4 ayda bir papilloma eksizyonu yapılmaktadır.

Key words: Bronchoscopy, papilloma, papillomaviridae, trachea.

Recurrent respiratory papillomatosis (RRP) is a rare respiratory condition associated with human papillomavirus (HPV) (1). It is characterized by exophytic, wart-like, squamous lesions within the respiratory tract (2). It frequently occurs in the larynx, and rarely, may be seen in lower airways of trachea, primary bronchi, and the lungs (1). Patients with 1

Department of Chest Diseases, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, İstanbul, Turkey 2 Department of Chest Diseases, Karabük University Faculty of Medicine, Karabük, Turkey 3 Department of Anesthesiology, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, İstanbul, Turkey

Anahtar Sözcükler: Bronkoskopi, papilloma, papilloma virüs ailesi, trakea.

RRP may develop bronchiectasis secondary to respiratory obstruction and infection. Malignant transformation rate of 2% to 3% within 10 years of diagnosis has been reported (3). Described herein is a case report of a 24-year-old male patient who presented with recurrent laryngotracheal papillomatosis. 1

Yedikule Göğüs Hastalıkları ve Göğüs Cerrahisi Eğitim ve Araştırma Hastanesi, Göğüs Hastalıkları Kliniği, İstanbul 2 Karabük Üniversitesi, Tıp Fakültesi, Göğüs Hastalıkları Anabilim Dalı, Karabük 3 Yedikule Göğüs Hastalıkları ve Göğüs Cerrahisi Eğitim ve Araştırma Hastanesi, Anestezi Kliniği, İstanbul

Submitted (Başvuru tarihi): 12.11.2016 Accepted (Kabul tarihi): 28.11.2016 Correspondence (İletişim): Mehmet Akif Özgül, Department of Chest Diseases, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, İstanbul, Turkey e-mail: aozgul1970@hotmail.com

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Respiratory Case Report

CASE A 24-year-old Caucasian male patient has been receiving treatment for 3 years for shortness of breath and hoarseness that had increased over time. His medical history revealed that problem began at fourth postpartum month when he developed hoarseness. Laryngoscopy was performed when he was about 1½ years of age. Papilloma was identified in the larynx and excised. However, complaints returned approximately 5 months later. He repeatedly underwent laryngoscopic excision until he reached 10 years of age, and no lesion distal to the vocal cord was identified in that period. The patient had no family history of papillomatosis or immunosuppression. He received treatment for pneumonia when he was 10 years old, and since then, tracheal lesions had developed in addition to those in the larynx. Following detection of tracheal papilloma, rigid bronchoscopy was performed approximately every 5 to 6 months to excise papillomas. Interferon alph-2a was used for a while and interval to excision of papillomas increased to 8 months; however, use of interferon alpha-2a was discontinued when time until excision required was reduced to just 6 months. Inhaled interferon was also used, but discontinued due to lack of any regression or delay in recurrence of symptoms. Physical examination indicated body mass index of 18, presence of hoarseness, and scoliosis with mild tendency to lean to left. During period before papilloma excisions he would develop mild stridor, which disappeared following excision. Other systemic examinations were normal except persistent rales at base of the left lung. The patient has been monitored at our outpatient clinic for 3 years, during which he has undergone papilloma excision at 3 to 4-month intervals. Chest radiography confirmed scoliosis with lean to the left (Figure 1). Chest tomography indicated deviation of the mediastinum to the left, prominent bronchiectasis involving posterobasal portion of the left lower lobe, and irregularity of the tracheal lumen in sections of the mediastinum (Figure 2). Blood cell count and routine biochemical tests were normal except for PO2 value of 72 mmHg in arterial blood gases sampled before bronchoscopy. Rigid bronchoscopy under general anesthesia revealed polypoid lesions resembling bunch of grapes, from level of vocal cord to the distal trachea, obliterating 90% of the lumen; after the carina, the lumen was patent. Debulking of polypoid lesions was performed with rigid tube. Cryotherapy and excision with biopsy forceps were also occasionally performed during the procedure. As lesions bled easily from beginning of the procedure merely when touched, short intubation and Cilt - Vol. 6 SayĹ - No. 2

mechanical ventilation were used due to deep desaturation, and then excision was resumed. Complete patency was achieved in the larynx and trachea following the procedure (Figure 3). Biopsy specimen was determined to be squamous cell papilloma. Written informed consent to publication was obtained from the patient.

Figure 1: Chest X-ray indicated scoliosis with a tendency to lean to the left

Figure 2: Polypoid lesion in (a) trachea and (b) bronchiectasis in the left lower lobe are visible in chest tomography images

Figure 3: Images taken (a) before and (b) after bronchoscopic excision

DISCUSSION RRP is a rare condition, most commonly associated with HPV types 6 and 11 (4). It equally affects women and men, and there is no difference in incidence by ethnicity. Although it is a benign condition, life-threatening respira-

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An Unusual Cause of Dyspnea and Hoarseness: A Recurrent Respiratory Papillomatosis | Özgül et al.

tory problems or malignant transformation may develop (3). RRP is the most common benign laryngeal lesion of childhood. Incidence has been reported as 4.3 per 100,000 children, and 1.8 per 100,000 adults per 100,000 in the USA (5). In pediatric series, RRP was typically diagnosed at between 2 and 4 years of age, with time to diagnosis of approximately 1 year (6). In our patient, symptoms started at fourth month of life; however, period between first diagnosis and onset of symptoms was approximately 1 year, in accordance with the literature. The disease frequently involves the vocal cord area of the larynx, and rarely, there is involvement of the distal respiratory tract (1). Entire aerodigestive tract may also be involved (4). Spontaneous remission may be experienced, or repeated surgical excision may be required (4). Direct transmission of HPV may occur via the birth canal during intrauterine period or during labor (7). Childhood RRP is potentially more threatening due to rapid growth in childhood (8). Clinically, hoarseness, chronic cough, recurrent pneumonia, retarded development in children, dysphagia, or stridor may occur (8). Our patient had no symptoms other than hoarseness and stridor. In this case, hoarseness remains following excision; however, stridor disappears after bronchoscopic excision. HPV types 6 and 11 are the most common viral subtypes, the latter being more aggressive (8). In our patient, we didn't attempt to identify the viral agent and conduct typology; diagnosis of RRP was based on clinical, macroscopic, and microscopic evaluations. As in present case, patients may require repeated bronchoscopic interventions in order to achieve and maintain airway patency. Although repeated surgical procedures may result in various complications, including synechia and narrowing in the laryngeal region, tracheoesophageal fistula, and stricture, no other effective treatment method has yet been developed to maintain airway patency. There is no report of specific complication during endobronchial treatment for RRP (9). However, as reported in previous publications, care should be taken for possible complications, such as hypoxia, bleeding, and arrhythmia associated with general anesthesia and rigid bronchoscopy (10,11). Although interferon alpha-2a, inhaled interferon, acyclovir, and cidofovir have been used, there is still no medical treatment that eliminates need for surgical treatment. In conclusion, RRP is a rare disease that may involve the entire respiratory system. It is particularly seen in children

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between 2 and 4 years of age, and in adults between 20 and 40 years of age. Although it is a benign disease, it requires close monitoring due to severely restricted airway and potential malignant transformation. Utmost care should be taken during bronchoscopy due to potential bleeding.

CONFLICTS OF INTEREST None declared.

AUTHOR CONTRIBUTIONS Concept - M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Planning and Design - M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Supervision M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Funding - M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Materials - M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Data Collection and/or Processing - M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Analysis and/or Interpretation - M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Literature Review - M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Writing - M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Critical Review - M.A.Ö., E.Ç., M.Ç., D.Ö.O.

YAZAR KATKILARI Fikir - M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Tasarım ve Dizayn M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Denetleme - M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Kaynaklar - M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Malzemeler - M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Veri Toplama ve/veya İşleme - M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Analiz ve/veya Yorum - M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Literatür Taraması - M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Yazıyı Yazan M.A.Ö., E.Ç., M.Ç., D.Ö.O.; Eleştirel İnceleme - M.A.Ö., E.Ç., M.Ç., D.Ö.O.

REFERENCES 1.

Ağgünlü L, Erbaş G. Recurrent respiratory papillomatosis with lung involvement. Diagn Interv Radiol 2009; 15:935.

2.

Goon P, Sonnex C, Jani P, Stanley M, Sudhoff H. Recurrent respiratory papillomatosis: an overview of current thinking and treatment. Eur Arch Otorhinolaryngol 2008; 265:147-51. [CrossRef]

3.

Frauenfelder T, Marincek B, Wildermuth S. Pulmonary spread of recurrent respiratory papillomatosis with malignant transformation: CT-findings and airflow simulation. Eur J Radiol Extra 2005; 56:11-6. [CrossRef]

4.

Derkay CS. Recurrent respiratory papillomatosis. Laryngoscope 2001; 111:57-69. [CrossRef]

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Respiratory Case Report

5.

Venkatesan NN, Pine HS, Underbrink MP. Recurrent respiratory papillomatosis. Otolaryngol Clin North Am 2012; 45:671-94. [CrossRef]

9.

6.

Derkay CS. Task force on recurrent respiratory papillomas. A preliminary report. Arch Otolaryngol Head Neck Surg 1995; 121:1386-91. [CrossRef]

7.

Mounts P, Shah KV, Kashima H. Viral etiology of juvenileand adult-onset squamous papilloma of the larynx. Proc Natl Acad Sci U S A 1982; 79:5425-9. [CrossRef]

10. Ernst A, Odell DD, Michaud G, Majid A, Herth FF, Gangadharan SP. Central airway stabilization for tracheobronchomalacia improves quality of life in patients with COPD. Chest 2011; 140:1162-8. [CrossRef]

8.

Carifi M, Napolitano D, Morandi M, Dall'Olio D. Recurrent respiratory papillomatosis: current and future perspectives. Ther Clin Risk Manag 2015; 11:731-8. [CrossRef]

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Derkay CS, Wiatrak B. Recurrent respiratory papillomatosis: a review. Laryngoscope. 2008; 118:1236-47. [CrossRef]

11. Stahl DL, Richard KM, Papadimos TJ. Complications of bronchoscopy: A concise synopsis. Int J Crit Illn Inj Sci 2015; 5:189-95. [CrossRef]

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Respir Case Rep 2017;6(2):82-85 DOI: 10.5505/respircase.2017.51423

OLGU SUNUMU

CASE REPORT

Pulmonary Tuberculosis with Fixed Drug Eruption to All First-Line Anti-Tuberculosis Drugs Tüm İlk Seçenek Antitüberküloz İlaçlarına Karşı Fiks İlaç Döküntüsü Gelişen Akciğer Tüberkülozu

RESPIRATORY CASE REPORTS

Gina Amanda, Fariz Nurwidya, Fathiyah Isbaniyah

Abstract

Özet

Tuberculosis (TB) is still one of the leading causes of mortality worldwide. Treatment with anti-TB drugs sometimes results in side effects for patients, including drug reactions, both allergic and non-allergic. Cutaneous adverse drug reaction is the most common side effect of anti-TB drugs, but severe reaction is rare. Here, we report rare case of a 34-year-old male who presented with pulmonary TB and fixed drug eruption to all first-line anti-TB therapies. After ingesting anti-TB regimen, multiple skin erosions and blisters occurred. Skin biopsy was performed and result was epidermis with subepidermal bullous. The patient’s condition deteriorated, he developed severe hypoxemia, and unfortunately, he died during fixed drug eruption treatment.

Tüberküloz tüm Dünya’da önemli bir mortalite nedeni olmaya devam etmektedir. Antitüberküloz tedavi sırasında kullanılan ilaçlarla, allerjik veya non-allerjik reaksiyonlar şeklinde yan etkiler ortaya çıkmaktadır. Ciddi reaksiyonlar nadir görülmekle beraber, ilaca bağlı cilt reaksiyonları antitüberküloz ilaçların en sık görülen yan etkileridir. Burada, ilk seçenek antitüberküloz ilaçların tümüne karşı fiks ilaç döküntüsü olan akciğer tüberkülozlu 34 yaşındaki erkek olguyu sunuyoruz. Antitüberküloz ilaçların alımından sonra hastanın tüm vücudunda çok sayıda erozyon ve kabarcıklar oluştu. Cilt biyopsisi yapıldı ve sonucu epidermal ve sub-epidermal büller olarak tanımlandı. Hastanın durumu ağır hiposemi nedeniyle kötüleşmeye başladı. Ne yazık ki, fiks ilaç döküntüsü tedavisi sırasında hasta vefat etti.

Key words: Adverse drug reaction, anti-tuberculosis drugs, drug eruption, tuberculosis.

Tuberculosis (TB) is still a health problem in the world, and one of the leading causes of morbidity and mortality, particularly in developing countries in Asia and Africa. First-line anti-TB therapy with rifampin, isoniazid, pyrazinamide, ethambutol, and streptomycin is still very effective for pulmonary TB. However, adverse drug reaction (ADR) may Department of Pulmonology and Respiratory Medicine, Indonesia University, Jakarta, Indonesia

Anahtar Sözcükler: İlaç yan etki, antitüberküloz ilaç, ilaç döküntüsü, tüberküloz.

complicate anti-TB treatment. Fixed drug eruption (FDE) is part of cutaneous ADR (CADR), which may be related to anti-TB drugs (1). FDE has been reported with rifampin, isoniazid, and ethambutol singly in some case reports (2-4). Presently described is rare case of pulmonary TB with FDE to all first-line anti-TB therapy. Endonezya Üniversitesi, Göğüs Hastalıkları Servisi, Jakarta, Endonezya

Submitted (Başvuru tarihi): 12.12.2016 Accepted (Kabul tarihi): 22.02.2017 Correspondence (İletişim): Gina Amanda, Department of Pulmonology and Respiratory Medicine, Indonesia University, Jakarta, Indonesia e-mail: gina_amanda@ymail.com

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Respiratory Case Reports

CASE A 34-year-old male patient was admitted to our hospital with chief complain of shortness of breath and productive cough. He had been diagnosed as pulmonary tuberculosis at a private clinic 1 year before admission. Oral firstline anti-TB drugs (combination of rifampin, isoniazid, pyrazinamide, and ethambutol) had been administered, but blisters appeared all over his body 4 days after consuming the drugs. Three months later, challenge test with rifampin and isoniazid was performed in district hospital, and blisters arose on the skin. Challenge test was discontinued until skin lesions healed. Following month, challenge test with pyrazinamide alone was initiated. Once again, similar skin lesions appeared and test was halted. Challenge test performed a month later with ethambutol also resulted in appearance of blisters. He was then referred to our hospital. Challenge test was re-initiated in outpatient clinic with rifampin and then with streptomycin injection, but blisters still appeared after each drug was administered singly. Desensitization test was planned, but the patient was lost to follow up after about 2 months. On physical examination, the patient was in moderately good general condition, respiratory rate was 32 breaths per minute, and oxygen saturation was 96% with oxygen flow of 3 liters per minute via nasal canula. Widespread erosion, crust, and hyperpigmentation were observed on the skin. Pulmonary auscultation revealed reduction of breath sounds in the left upper lung field and bronchovesicular sound with crackles in bilateral lung field. Chest X-ray revealed bullae in the left upper lung field with diffuse infiltrates (Figure 1). Acid-fast bacilli of sputum were positive and Xpert MTB/RIF test (Cepheid, Inc., Sunnyvale, CA, USA) of sputum result was Mycobacterium tuberculosis sensitive with rifampin. Antinuclear antibody test and rheumatoid factor were also checked to eliminate possibility of autoimmune etiology and results were negative. HIV antibody test was also negative. Skin biopsy performed at outpatient clinic revealed epidermis with subepidermal bullae containing eosinophil, fibrotic dermis, and chronic inflammatory cells (Figure 2). Conclusion was bullous drug eruption and was managed with oral steroid and topical cream. Anti-TB drug desensitization was planned for after skin lesions healed, but the patient’s condition deteriorated. He died as result of severe hypoxemia.

Cilt - Vol. 6 SayÄą - No. 2

Figure 1: Chest X-ray revealed diffuse infiltrates with bullae in the upper left lung field

Figure 2: Histopathology examination of skin biopsy revealed subepidermal bullous (arrow) (H&E x100)

DISCUSSION The Anti-TB drugs used for pulmonary TB treatment are associated with ADR. ADR may include immunologicallymediated drug hypersensitivity (drug allergy) or nonimmune mediated/idiosyncratic reactions. Mechanism of drug allergy may be immunoglobulin E (Ig-E) or non-Ig-E mediated (5,6). Anti-TB drugs contain low molecular compounds that may induce allergic reaction through antigen presenting cell (APC)-hapten binding. Hapten is a low molecular substance that binds to carrier, such as protein, before APC presentation. According to classification of Coombs and Gell, allergic reaction is divided into 4 types, and most reactions to low-molecular-weight drugs are type I and type IV (7). CADR is part of ADR and one of the most commonly observed side effects of antiTB drugs. There are several types of CADR, such as mor-

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Pulmonary Tuberculosis with Fixed Drug Eruption to All First-Line Anti-Tuberculosis Drugs | Amanda et al.

biliform and maculopapular drug eruption, exfoliative dermatitis, lichenoid drug eruption, cutaneous vasculitis, FDE, Steven Johnson Syndrome, and toxic epidermal necrolysis (5). FDE has many variant forms of lesion, including solitary or small number of erythematous macules and widespread lesion with blisters. Lesion can appear on any part of the skin or mucous membranes within a day to a few weeks after administering the causative drug. It resolves with residual hyperpigmentation (8,9). Generalized bullous drug eruption is severe form of FDE with mortality rate of 22% (10). In our patient, blisters appeared after administration of combination of anti-TB drugs and after challenge test with all anti-TB drugs. Diagnosis of FDE was confirmed by histopathology examination. There are limited available data about incidence of antiTB drug related CADR. Severe CADR may result in discontinuation of anti-TB drug use and thereby increase morbidity and even mortality (1). Nahid et al. (11) found that HIV status, positive result of sputum smear at baseline, and drug interruption during intensive phase was associated with high mortality rate in TB patient. Severe FDE in our patient interrupted pulmonary TB treatment and time was required for healing of skin lesions before re-starting anti-TB drug administration. Poor outcome in this patient was related not only to severe FDE, but also to patient declining to continue therapy. Reintroducing anti-TB treatment following TB-associated CADR is important to diminish mortality rate. There are 2 methods to this process: challenge and desensitization. Challenge test aims to identify the offending drug and eliminate it from the regimen of therapy, whereas desensitization seeks to relieve immune response to causal drug by prolonged or repeated stimulus. Neither is recommended for drugs that have been associated with severe allergic reaction. However, exclusion from challenge test can lead to high risk of death, so risk-benefit ratio should be considered before performing these tests on patient with severe allergic reaction (5). Challenge test protocol may begin with isoniazid 50 mg on day 1. If there is no allergic reaction, the dose may be increased to 300 mg on day 2. This dose should continue for 4 days if allergic reaction does not occur. Drugs are then added in order and dose specified in Table 1. Dose of each drug is increased until recommended dose is achieved and is then continued for 4 days. If allergic reaction occurs during challenge test, desensitization test may be performed for the causative drug. General protocol for desensitization test may be initiated with 1/10 of

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the day 1 dose. Each dose is doubled and administered twice daily until recommended daily dose has been achieved and it is continued for 3 days before it may be replaced by once daily dosing. If allergic reaction occurs during desensitization process, dose is decreased to the highest dose that did not cause any allergic reaction and increased in smaller increments (12). Tablo 1: The Challenge Test Protocol Drug

Challenge Doses Day 1 Day 2

Isoniazid

50 mg

300 mg

Rifampicin

75 mg

300 mg

Pyrazinamide

250 mg

1000 mg

Ethambutol

100 mg

500 mg

Streptomycin

125 mg

500 mg

In conclusion, CADR is one of possible side effects of anti-TB drugs. Severe reaction will interrupt pulmonary TB treatment for long period of time and will likely increase either complication of underlying disease or mortality risk. Re-introducing anti-TB drugs is required for patients with CADR before they continue anti-TB treatment. Although severe reaction in CADR is rare, it may be fatal. Close monitoring and proper management are needed for patient with this case.

ACKNOWLEDGMENT We would like to express our sincere gratitude to Dr. Dianiati Kusumo Sutoyo of the Immunology division, Department of Pulmonology and Respiratory Medicine, Faculty of Medicine Universitas Indonesia, Persahabatan Hospital for her valuable advice and support for this case report, Dr. Euis Muthmainah of the Department of Dermatology and Venerology Persahabatan Hospital for her advice and support during the treatment of the patient and Dr. Ruth Emalian Sembiring of Department of Pathology Persahabatan Hospital for providing the microscopic histopatology figure.

CONFLICTS OF INTEREST None declared.

AUTHOR CONTRIBUTIONS Concept - G.A., F.N., F.I.; Planning and Design - G.A., F.N., F.I.; Supervision - G.A., F.N., F.I.; Funding - G.A., F.N.; Materials - G.A.; Data Collection and/or Processing - G.A.; Analysis and/or Interpretation - G.A., F.I.; www.respircase.com


Respiratory Case Reports

Literature Review - G.A.; Writing - G.A.; Critical Review G.A., F.N.

6.

Thong BY, Tan TC. Epidemiology and risk factors for drug allergy. Br J Clin Pharmacol 2011; 71:684-700. [CrossRef]

YAZAR KATKILARI

7.

Fikir - G.A., F.N., F.I.; Tasarım ve Dizayn - G.A., F.N., F.I.; Denetleme - G.A., F.N., F.I.; Kaynaklar - G.A., F.N.; Malzemeler - G.A.; Veri Toplama ve/veya İşleme - G.A.; Analiz ve/veya Yorum - G.A., F.I.; Literatür Taraması G.A.; Yazıyı Yazan - G.A.; Eleştirel İnceleme - G.A., F.N.

Schnyder B, Brockow K. Pathogenesis of drug allergy current concepts and recent insights. Clin Exp Allergy 2015; 45:1376-83. [CrossRef]

8.

Shiohara T. Fixed drug eruption: pathogenesis and diagnostic tests. Curr Opin Allergy Clin Immunol 2009; 9:316-21. [CrossRef]

9.

Sehgal VN, Srivastava G. Fixed drug eruption (FDE): changing scenario of incriminating drugs. Int J Dermatol 2006; 45:897-908. [CrossRef]

REFERENCES 1.

Tan WC, Ong CK, Kang SC, Razak MA. Two years review of cutaneous adverse drug reaction from first line anti-tuberculous drugs. Med J Malaysia 2007; 62:143-6.

2.

John SS. Fixed drug eruption due to rifampin. Lepr Rev 1998; 69:397-9. [CrossRef]

3.

Scheid P, Kanny G, Trechot P, Rosner V, Menard O, Vignaud JM, et al. Isoniazid-induced bullous skin reaction. Allergy 1999; 54:294-6. [CrossRef]

4.

Bakayoko AS, Kaloga M, Kamagate M, Kone Z, Daix AT, Ohui E, et al. Fixed drug eruption after taking ethambutol. Rev Mal Respir 2015; 32:48-51. [CrossRef]

5.

Lehloenya RJ, Dheda K. Cutaneous adverse drug reactions to anti-tuberculosis drugs: state of the art and into the future. Expert Rev Anti Infec Ther 2012; 10:475-86. [CrossRef]

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10. Lipowicz S, Sekula P, Ingen-Housz-Oro S, Liss Y, Sassolas B, Dunant A, et al. Prognosis of generalized bullous fixed drug eruption: comparison with Stevens-Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol 2013; 168:726-32. [CrossRef] 11. Nahid P, Jarlsberg LG, Rudoy I, de Jong BC, Unger A, Kawamura LM, et al. Factors associated with mortality in patients with drug-susceptible pulmonary tuberculosis. BMC Infec Dis 2011; 11:1. [CrossRef] 12. Philadephia tuberculosis control program. Guidelines for the management of adverse drug effects of antimycobacterial agents. Philadelphia: Philadephia tuberculosis control program; 1998. p. 5-6.

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Respir Case Rep 2017;6(2):86-89 DOI: 10.5505/respircase.2017.57855

OLGU SUNUMU

CASE REPORT

Coexistence of Pulmonary Tuberculosis and Sarcoidosis Pulmoner Tüberküloz ve Sarkoidoz Birlikteliği

RESPIRATORY CASE REPORTS

Serap Argun Barış1, Adnan Batman2, Salih Küçük1, Sevtap Gümüştaş3

Abstract

Özet

Tuberculosis (TB) and sarcoidosis are granulomatous diseases with different etiologies and management; however, they have similar clinical and histological characteristics. Coexistence of TB and sarcoidosis is extremely rare. Presently described is a case of coexistence of pulmonary tuberculosis and sarcoidosis confirmed microbiologically and histopathologically.

Sarkoidoz ve tüberküloz farklı etyoloji ve tedaviye sahip ancak klinik ve histolojik olarak birbiri ile sıkça karışan hastalıklardır. Tüberküloz ve sarkoidoz birlikteliği nadirdir. Burada mikrobiyolojik ve histopatolojik olarak kanıtlanmış tüberküloz ve sarkoidoz birlikteliği olan olgu sunulmaktadır.

Key words: Sarcoidosis, tuberculosis, coexistence, diagnosis.

Tuberculosis (TB) and sarcoidosis are granulomatous diseases with different etiologies and management; however, they have similar clinical and histological characteristics (1). Distinguishing sarcoidosis from pulmonary TB can sometimes be a

1

Department of Pulmonary Diseases, Kocaeli University Faculty of Medicine, Kocaeli, Turkey 2 Department of Internal Medicine, Mus Government Hospital, Mus, Turkey 3 Department of Radiology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey

Anahtar Sözcükler: Sarkoidoz, tüberküloz, birliktelik, tanı.

great challenge to physicians, especially in developing countries where there is high prevalence of TB (2). Coexistence of these 2 diseases is extremely rare (3-5). Case of coexistence of TB and sarcoidosis is described in this report.

1

Kocaeli Üniversitesi Tıp Fakültesi, Göğüs Hastalıkları Anabilim Dalı, Kocaeli 2 Muş Devlet Hastanesi, İç Hastalıkları Bölümü, Muş 3 Kocaeli Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, Kocaeli

Submitted (Başvuru tarihi): 29.12.2016 Accepted (Kabul tarihi): 13.02.2017 Correspondence (İletişim): Serap Argun Barış, Department of Pulmonary Diseases, Kocaeli University Faculty of Medicine, Kocaeli, Turkey e-mail: serapargun2002@yahoo.com

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Respiratory Case Reports

CASE A 50-year-old woman presented at outpatient clinic with fatigue, nonproductive cough and backache of 2-month duration. She had no history of smoking or medication. There was no history of contact with TB and vital signs were normal. Crackles at base of both lungs were heard on physical examination. There was bilateral hilar enlargement, increased interstitial and reticulonodular opacity on chest X-ray (Figure 1). Thorax CT revealed bilateral enlargement of mediastinal lymph nodes, septal thickening, and parenchymal perilymphatic nodules (Figures 2a and b).

Figure 1: Initial chest X-ray revealed bilateral hilar enlargement, and increased interstitial and reticulonodular opacities

There were no laboratory abnormalities except increased level of angiotensin converting enzyme (ACE), C-reactive protein (CRP) and increased sedimentation rate [ACE: 110 (normal range: 0-52 U/L), sedimentation rate: 48/h, CRP: 2.5 mg/dL (normal range: 0-0.5 mg/dL)]. Tuberculin skin test anergy was noted, though she had bacillus Calmette–Guérin scar. Carbon monoxide diffusion test was 44% of predictive value. Fiberoptic bronchoscopy revealed enlarged right secondary carina. Bronchoalveolar lavage, bronchial washing, and bronchial mucosal biopsy were performed during bronchoscopy. Fine needle aspiration of subcarinal lymph node was nondiagnostic. Gram and acid-fast bacilli (AFB) staining of bronchial lavage material was negative. There was lymphocytic alveolitis and CD4/CD8 ratio was 4.5. Pathological evaluation of mucosal biopsy from right secondary carina revealed granulomatous inflammation. Immunohistochemical evaluation of biopsy specimen revealed immunoreactivity with CD68 in epithelial histiocytes (Figures 3 A and B). Histopathological findings of lung biopsy were consistent with sarcoidosis. The patient was diagnosed with stage 2 sarcoidosis. Consultation was arranged with departments of internal disease, cardiology, and ophthalmology. There was no involvement of the eye, skin, or heart. As clinical condition was stable, corticosteroid treatment was not initiated. Follow-up of clinical and radiological progress was planned; however, Lowenstein Jensen medium culture of bronchial lavage was positive on 25th day. She was diagnosed with TB and treated with rifampicin 600 mg, isoniazid 300 mg, ethambutol 1500 mg, and pyrazinamide 2000 mg on a daily basis for 2 months, after which pyrazinamide and ethambutol were excluded, and dual therapy was continued for 4 months. The patient was in good clinical condition and there was radiological improvement of parenchymal nodules, though no change in lymph nodes or interstitial opacities after anti-TB treatment (Figure 4). Clinical and microbiological assessments were evaluated as TB coexisting with sarcoidosis.

DISCUSSION

Figure 2a and b: Initial thorax computed tomography findings were enlarged bilateral hilar and mediastinal lymph nodes, septal thickening, and parenchymal perilymphatic nodules Cilt - Vol. 6 Sayı - No. 2

TB and sarcoidosis are chronic granulomatous diseases with similar clinical and histopathological characteristics. Differential diagnosis of sarcoidosis and TB is a great challenge to clinicians, particularly in countries with high prevalence of TB (6). TB is infectious disease caused by Mycobacterium tuberculosis and it is still a major health problem worldwide. It is characterized by caseating granuloma and treatment is focused on elimination of micro-

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Coexistence of Pulmonary Tuberculosis and Sarcoidosis | Argun BarÄąĹ&#x; et al.

organism (7). It is often difficult to diagnose, especially when caseous necrosis is not seen and AFB staining is negative in specimens of TB patients (8). Sarcoidosis is a multisystem disease of unknown etiology, characterized by presence of non-caseating granuloma in the lungs, lymph nodes, and other organs (6).

Figure 3a and b: (a) Epithelial histiocyte group under surface epithelium (H&E x400); (b) Immunoreactivity with CD68 in epithelial histiocytes (CD68 x400)

Figure 4: Follow-up chest X-ray after antituberculosis treatment revealed radiological improvement of parenchymal nodules but no change in lymph nodes or interstitial opacities

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The role of mycobacterium as etiological agent in development of sarcoidosis has been investigated in the literature due to clinical and histological similarities of these diseases (8,9). Current approaches indicate increased prevalence of sarcoidosis in TB-endemic regions (8). In a meta-analysis, it was suggested that there is association between mycobacterium (both Mycobacterium tuberculosis complex and nontuberculous) and sarcoidosis (9). Sarcoidosis occasionally develops in patients previously treated for tuberculosis (3,6,10). Less commonly, TB develops as an opportunistic infection in patients following corticosteroid treatment for sarcoidosis (5). Coexistence of TB and sarcoidosis is rare (2-5). Clinical and radiological features of TB and sarcoidosis overlap quite a bit and therefore, diagnostic dilemma often persists. Clinical presentation of sarcoidosis is generally nonspecific. Constitutional symptoms such as fever, fatigue, and weight loss are present in approximately one-third of patients, similar to our patient. Chest X-ray usually shows hilar and mediastinal enlargement. Interstitial or nodular opacities suggesting interstitial lung disease may also be seen. High resolution CT of thorax shows thickening of the interlobular septa and peribronchovascular bundles and perilymphatic nodules (2). Clinical and radiological findings of this case were consistent with the literature. Diagnosis is established most securely when clinical and radiological findings are supported by histological evidence (2). In this case, diagnosis of sarcoidosis was also supported by anergic tuberculin skin test, decreased diffusing capacity of the lungs, increased serum ACE, increased CD4/CD8 levels in bronchoalveolar lavage fluid, and non-caseating granulomatous inflammation in mucosal biopsy of lung. Exclusion of TB is important since corticosteroids are mainstay treatment for sarcoidosis (2). It is suggested that corticosteroid therapy should not be initiated until there is microbiological confirmation of mycobacterium culture in cases of dilemma in diagnosis between TB and sarcoidosis (7). In our case, radiological pattern was consistent with stage 2 sarcoidosis. AFB stain of the bronchial lavage was negative. Corticosteroid treatment was not implemented until mycobacterium culture results were returned due to high prevalence of TB in our country. The patient was also diagnosed with TB based on positive Lowenstein-Jensen medium culture of bronchial lavage. She was treated with anti-TB drugs for 6 months. There was radiological improvement of parenchymal nodules but no change in lymph nodes or interstitial opacities www.respircase.com


Respiratory Case Reports

after anti-TB treatment. Clinical and microbiological assessments were TB coexisting with sarcoidosis. In conclusion, differential diagnosis of granulomatous inflammation is difficult for clinicians. It is suggested that even if findings point to one of these diseases, coexistence of sarcoidosis and TB should be kept in mind.

2.

Badar F, Azfar SF, Ahmad I, Yasmeen S, Kirmani S. Diagnostic difficulties in differentiating sarcoidosis from tuberculosis. Oman Med J 2011; 26:210-21. [CrossRef]

3.

Shah JR, Hede J, Mathur RS. Diagnostic criteria of tuberculous sarcoidosis. Lung India 2009; 26:86-8. [CrossRef]

4.

Wong CF, Yew WW, Wong PC, Lee J. A case of concomitant tuberculosis and sarcoidosis with mycobacterial DNA present in the sarcoid lesion. Chest 1998; 114:626- 9. [CrossRef]

5.

Oluboyo PO, Awotedu AA, Banach L. Concomitant sarcoidosis in a patient with tuberculosis: first report of association in Africa. Cent Afr J Med 2005; 51:123-5.

6.

Gupta D, Agarwal R, Aggarwal AN, Jindal SK. Sarcoidosis and tuberculosis: the same disease with different manifestations or similar manifestations of different disorders. Curr Opin Pulm Med 2012; 18:506-16. [CrossRef]

7.

Mise K, Goic-Barisic I, Puizina-Ivic N, Barisic I, Tonkic M, Peric I. A rare case of pulmonary tuberculosis with simultaneous pulmonary and skin sarcoidosis: a case report. Cases J 2010; 3:24. [CrossRef]

8.

Mortaz E, Masjedi MR, Matroodi S, Abedini A, Kiani A, Soroush D, et al. Concomitant patterns of tuberculosis and sarcoidosis. Tanaffos 2013; 12:6-9.

9.

Gupta D, Agarwal R, Aggarwal AN, Jindal SK. Molecular evidence for the role of mycobacteria in sarcoidosis: a meta-analysis. Eur Respir J 2007; 30:508-16. [CrossRef]

CONFLICTS OF INTEREST None declared.

AUTHOR CONTRIBUTIONS Concept - S.A.B., A.B., S.K., S.G.; Planning and Design S.A.B., A.B., S.K., S.G.; Supervision - S.A.B., A.B., S.K., S.G.; Funding -; Materials -; Data Collection and/or Processing - S.A.B., S.G., A.B.; Analysis and/or Interpretation - S.A.B., S.K., S.G.; Literature Review - G.A.K.; Writing - S.A.B.; Critical Review - S.A.B., S.G.

YAZAR KATKILARI Fikir - S.A.B., A.B., S.K., S.G.; Tasarım ve Dizayn - S.A.B., A.B., S.K., S.G.; Denetleme - S.A.B., A.B., S.K., S.G.; Kaynaklar -; Malzemeler -; Veri Toplama ve/veya İşleme S.A.B., S.G., A.B.; Analiz ve/veya Yorum - S.A.B., S.K., S.G.; Literatür Taraması - G.A.K.; Yazıyı Yazan - S.A.B.; Eleştirel İnceleme - S.A.B., S.G.

REFERENCES 1.

Mandal SK, Ghosh S, Mondal SS, Chatterjee S. Coexistence of pulmonary tuberculosis and sarcoidosis: a diagnostic dilemma. BMJ Case Rep 2014. [CrossRef]

Cilt - Vol. 6 Sayı - No. 2

10. Jindal SK, Gupta D, Aggarwal AN. Sarcoidosis in developing countries. Curr Opin Pulm Med 2000; 6:448- 54. [CrossRef]

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Respir Case Rep 2017;6(2):90-95 DOI: 10.5505/respircase.2017.98705

OLGU SUNUMU

CASE REPORT

PET-BT'de Yüksek Düzeyde FDG Tutulumu Olan Mediastinal Lenfadenopatilerde Granülamatöz Hastalıklar Düşünülmelidir* Granulomatous Diseases Should be Considered in Mediastinal Lymphadenopathies with High F-18 FDG Uptake on PET-CT Scans

RESPIRATORY CASE REPORTS

Burçin Çelik1, Muhammed Ali Yılmaz1, Mehmet Gökhan Pirzirenli1, Murathan Şahin2

Özet

Abstract

Granülomatöz hastalıklar ülkemizde oldukça sık görülmektedir. Tüberküloz ve sarkoidoz bu hastalıklar içerisinde en başta gelenlerdir. Tüberküloz sıklıkla akciğerleri tutmasına rağmen bazı olgularda mediastinal lenf tutulumu şeklinde de ortaya çıkmaktadır. Sarkoidoz ise sıklıkla mediastinal ve hiler lenfadenopatiler şeklinde karşımıza çıkmaktadır. Bu makalede PET-BT incelemelerinde mediastinal maligniteyi taklit eden, yüksek düzeyde F-18 FDG tutulumu olan granülamatöz lenfadenit olgularını sunmayı amaçladık. Kliniğimize PET-BT görüntülerinde patolojik FDG tutulumu olan mediastinal LAP nedeniyle üç hasta başvurdu. Hastaların ikisinde öksürük ve nefes darlığı şikâyeti, birisi meme kanseri, uterus kanseri ve tiroit kanserinden ameliyat edilmişti. İki olgunun videomediastinoskopik lenf nodu biyopsi sonucu kazeifiye granülomatöz iltihabi olay olarak rapor edildi. Nefes darlığı nedeniyle tetkik edilen hastanın PET-BT'de subkarinal lenf nodu ve sol interlober lenf nodlarında patolojik FDG tutulumu izlendi. Bu olgunun videomediastinoskopik lenf nodu biyopsi sonucu nonkazeifiye granülomatöz iltihabi olay olarak rapor edildi. Ülkemizde tüberküloz ve sarkoidoz gibi granülamatöz hastalıklar yanlış pozitif FDG PET nedenleri arasında en sık görülenlerdir. Olgularımızdaki gibi yüksek FDG tutulumu olanlarda maligniteyi ekarte edebilmek için doku biyopsisi gereklidir.

Granulomatous diseases are quite common in our country; tuberculosis (TB) and sarcoidosis are the most common. TB mostly involves the lungs; however, in some cases, it may involve the mediastinal lymph nodes. Sarcoidosis, on the other hand, often reveals itself as mediastinal or hilar lymphadenopathy (LAP). Presently described are cases of granulomatous lymphadenitis that mimicked mediastinal malignancy in positron emission tomography-computed tomography (PET-CT) scanning and had high fludeoxyglucose (FDG) uptake. Three patients whose PET-CT scans revealed pathological FDG uptake due to mediastinal LAP were admitted to our clinic. Two had cough and dyspnea, and third had operated breast cancer, uterine cancer, and thyroid cancer. Videomediastinoscopic biopsies of 2 patients were reported as caseating granulomatous inflammation. In patient who was examined for dyspnea, PET-CT revealed pathological FDG uptake in subcarinal lymph nodes and the left interlobar lymph nodes. Videomediastinoscopic lymph node biopsy of this patient was reported as non-caseating granulomatous inflammation. Granulomatous diseases, such as TB and sarcoidosis, are the most common cause of false-positive FDG PET scans in our country. In cases with high FDG uptake, tissue biopsy can exclude malignancy.

Anahtar Sözcükler: Granülomatöz hastalık, lenfadenopati, mediasten, PET-BT.

Key words: Granulomatous disease, lymphadenopathy, mediastinum, PET-CT.

1

1 Ondokuz Mayıs Üniversitesi Tıp Fakültesi, Göğüs Cerrahisi AnaDepartment of Thoracic Surgery, Ondokuz Mayıs University bilim Dalı, Samsun Faculty of Medicine, Samsun, Turkey 2 2 Ondokuz Mayıs Üniversitesi Tıp Fakültesi, Nükleer Tıp Anabilim Department of Nuclear Medicine, Ondokuz Mayıs University Dalı, Samsun Faculty of Medicine, Samsun, Turkey Başvuru tarihi (Submitted): 29.12.2016 Kabul tarihi (Accepted): 20.02.2017

İletişim (Correspondence): Burçin Çelik, Ondokuz Mayıs Üniversitesi Tıp Fakültesi, Göğüs Cerrahisi Anabilim Dalı, Samsun e-mail: cburcin@hotmail.com *Makale Türk Toraks Derneği 17. Yıllık Kongresi poster sunumu olarak sunulmuştur. 2-6 Nisan 2014, Antalya.

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Respiratory Case Reports

Günümüzde akciğer ve mediastinal malignitelerinin tanısında ve evrelendirilmesinde pozitron emisyon tomografisi bilgisayarlı-tomografi (PET-BT) oldukça sık kullanılmaktadır. PET-BT'de, mediastinal lezyonlarda fluoro-2-deoksi-glikoz (FDG) tutulumunun malignite için yüksek sensitivite ve spesifisiteye sahip olduğu bilinmektedir. Ancak özellikle infeksiyon veya inflamasyonla ilişkili benign durumlarda da PET-BT'de artmış FDG tutulumu olmakta ve granülomatöz hastalıklar bu benign durumların başında gelmektedir (13). Granülomatöz hastalıklar ülkemizde oldukça sık görülmekte olup tüberküloz ve sarkoidoz bu hastalıklar içersinde en başta gelenlerdir. Tüberküloz sıklıkla akciğerleri tutmasına rağmen bazı olgularda izole mediastinal lenf tutulumu şeklinde ortaya çıkabilmektedir (4). Sarkoidoz ise sıklıkla mediastinal ve hiler lenfadenopatiler (LAP) şeklinde görülmektedir (1). Bu çalışmada PET-BT incelemelerinde mediastinal maligniteyi taklit eden, yüksek düzeyde FDG tutulumu olan granülamatöz lenfadenit olgularını sunmayı amaçladık (Tablo 1).

8,61), paraözofageal (SUDmaks: 15,05), sağ hiler (SUDmaks: 17,93), sol hiler (SUDmaks: 14,38), abdominal bölgede interaortakaval (SUDmaks: 8,36) ve prekaval (SUDmaks: 4,36) ve sağ inguinal (SUDmaks: 18,1), sol inguinal (SUDmaks: 13,2) multipl lenf adenopatiler tespit edildi (Şekil 1).

Şekil 1: Meme kanseri, over kanseri ve troit kanseri tanıları olan 60 yaşında kadın hastanın grafisinde mediastinal genişleme, PET-BT'de; sağ üst ve alt paratrakeal, sol alt paratrakeal, subkarinal, bilateral hiler, intraabdominal ve inguinal lenf nodlarında artmış FDG akümülasyonu.

OLGU Olgu 1: Altmış yaşında aktif bir şikâyeti olmayan kadın hasta 2001 yılında meme infiltratif duktal karsinom, 2009 yılında over adeno kanseri, 2010 yılında hurtle hücreli tiroid kanseri nedeniyle ameliyat edilmiş ve onkoloji kliniği tarafından takip edilmektedir. Rutin poliklinik kontrolleri sırasında çekilen PET BT'de, sağ üst ve alt paratrakeal bölgede en büyüğü 24x15 mm ebadında (SUDmaks: 20,34) olmak üzere; sol alt paratrakeal (SUDmaks: 15,5), subaortik (SUDmaks: 14,93), subkarinal (SUDmaks:

Tümör konseyinde değerlendirilen hastaya servikal mediastinoskopi kararı alındı. Genel anestezi altında uygulanan videomediastinoskopide sağ üst ve alt paratrakeal, sol alt paratrakeal bölgede tespit edilen lenf nodları çıkartıldı. Biyopsi ile alınan lenf nodlarının histopatolojik inceleme sonucu kazeifiye granülamatöz iltihabi olay olarak rapor edildi. Göğüs hastalıkları kliniği tarafından antitüberküloz tedavi başlanan hastanın yaklaşık 1 yıl sonra çekilen PET-BT'sinde daha önce izlenen patolojik FDG tutulumu olan tüm lenf nodlarının regrese olduğu ve görüntülemede izlenmediği tespit edildi (Şekil 2).

Tablo 1: Olguların demografik özellikleri, belirlenen LAP lokalizasyonları, SUDmaks değerleri ve mediastinokopi ile elde edilen histopatolojik tanılar. Olgu Yaş Cinsiyet LAP SUDmaks Patolojik Lokalizasyonu değeri Tanı 2R, 4R 20,3 Opere meme ve 60 Kadın Tüberküloz uterus kanseri 10R 17,9

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Öksürük ve nefes darlığı

60

Öksürük ve nefes darlığı

60

Kadın

Kadın

2R, 4R, 7, 8

18,81

6

14

4R, 4L, 7,

21(7)

10R, 10L, 11

28 (11)

Tüberküloz

Tüberküloz

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PET-BT'de Yüksek Düzeyde FDG Tutulumu Olan Mediastinal Lenfadenopatilerde Granülamatöz Hastalıklar Düşünülmelidir | Çelik ve ark.

Şekil 3: Altmış bir yaşında bayan hastanın grafisinde bilateral hiler ve mediastinal genişleme, PET-BT’de; yüksek mediastinal, prevasküler, paraaortik, subaortik, subkarinal, bilateral hiler lenf nodlarında artmış FDG akümülasyonu.

Şekil 2: Birinci olgu antitüberküloz tedavi aldıktan yaklaşık bir yıl sonra çekilen PET-BT'sinde daha önce izlenen patolojik FDG tutulumu olan tüm lenf nodları regrese.

Olgu 2: Altmış bir yaşında kadın hasta sekiz aydır süren öksürük şikâyeti ile göğüs hastalıkları kliniğine başvurmuş. Hastanın toraks bilgisayarlı tomografisinde; mediastende tüm alanlarda ve bilateral hiler en büyüğü 2 cm çapından çok sayıda lenf adenopati, her iki akciğerde üst loblarda daha fazla olmak üzere yer yer mozaik atenüasyon alanları izlenmiş. Hastaya lokal anestezi altında fleksibl bronkoskopi uygulanmış ve endobronşiyal lezyon izlenmemiş, subkarinal yerleşimli lenf noduna WANG biyopsi uygulanmış. Bronkoskopi sırasında alınan bronkoalveoler lavaj ve WANG biyopsinin histopatolojik incelemesi sonucunun tanısal gelmemesi üzerine hastaya PET-BT çekilmiş. PETBT'de; sağda yüksek mediastinal (SUDmaks: 17,58), solda yüksek mediastinal ve prevasküler (SUDmaks: 13,59), sağ üst ve alt paratrakeal konglomere (SUDmaks: 18,81), subkarinal-paraözofageal (SUDmaks: 18,81), sol hiler (SUDmaks: 15,77), sağ hiler (SUDmaks: 12,97) multipl lenf nodlarında artmış FDG tutulumu ve ayrıca sağ akciğer üst lob anterior segmentte (SUDmaks: 7,53), sağ alt lob laterobazal segmentte (SUDmaks: 6,42), sol akciğer alt lob posterobazal segmentte (SUDmaks: 8,97) infiltratif hiperdens alanlar izlendi. Yine abdominal bölgede çöliyak (SUDmaks: 14,71) ve postkaval (SUDmaks: 12,71) lenf nodlarında artmış FDG akümülasyonu izlendi (Şekil 3).

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Sarkoidozis ve malignite ön tanıları ile hastaya genel anestezi altında servikal videomediastinoskopi uygulandı. Videomediastinoskopide sağ üst ve alt paratrakeal yerleşimli konglomere lenf nodlarından biyopsiler alındı. Alınan biyopsilerin histopatolojik inceleme sonucu kazeifiye granülomatöz iltihabi olay olarak rapor edildi. Antitüberküloz tedavi başlanan hastanın 7 ay sonra kontrol amacıyla çekilen toraks BT'de tüm mediastinal lenf nodlarının regrese olduğu tespit edildi. Olgu 3: Bir yıldır süren nefes darlığı şikâyeti ile başvuran 48 yaşında kadın hastanın akciğer grafisinde mediastinal genişleme ve bilateral hiler dolgunluk izlenmesi üzerine toraks BT çekildi. Toraks BT'de; sağ paratrakeal, prevasküler ve her iki hiler bölgede çapı 1 cm'e ulaşan lenf adenopatiler ve akciğer parankiminde milimetrik nodüller izlendi. Hastanın PET-BT'sinde; paraaortik ve aortikopulmoner pencerede (SUDmaks: 10,0), sağ alt paratrakeal (SUDmaks: 9,4), sol alt paratrakeal (SUDmaks: 5,0), subkarinal (SUDmaks: 21,9), sağ hiler (SUDmaks: 22,7), sol hiler (SUDmaks: 28,7), sağ iliak eksternal multipl hipermetabolik LAP (SUDmaks: 10,1) ayrıca sağ akciğer alt lob superior segmentte hipermetabolik, 12x11 mm ebadında (SUDmaks: 3,1) nodül izlendi (Şekil 4). Hastaya fleksibl bronkoskopi uygulandı ve endobronşiyal lezyon izlenmemesi üzerine servikal videomediastinoskopi kararı alındı. Genel anestezi altında yapılan servikal videomediastinoskopi ile sağ alt paratrakeal ve subkarinal lenf nodlarından biyopsiler alındı. Lenf nodu biyopsilerinin histopatolojik inceleme sonucu nonkazeifiye granülamatöz lenfadenit olarak rapor edildi ve hasta ileri tetkik ve tedavi amacıyla göğüs hastalıkları kliniğine yönlendirildi. Sarkoidoz tanısı konulan ve başka sistem tutulumu olmayan hastaya tedavi verilmedi ve halen takip edilmektedir. www.respircase.com


Respiratory Case Reports

Şekil 4: Üçüncü olgunun akciğer grafisinde bilateral hiler dolgunluk, PET BT'de; bilateral alt paratrakeal, subkarinal hiler ve sol interlober konglomere lenf nodlarında patolojik FDG tutulumu.

TARTIŞMA Akciğer ve mediastinal lezyonların malign-benign ayrımında PET-BT'nin kullanıma girmesiyle birlikte gereksiz biyopsiler ve gereksiz cerrahi girişimlerin sayısı günümüzde oldukça azalmıştır. Ancak PET-BT'deki yanlış pozitiflik granülomatöz hastalıkların endemik olduğu bölgelerde ayırıcı tanıda halen sorun olmaktadır. Ülkemizde tüberküloz ve sarkoidoz gibi granülamatöz hastalıklar PET-BT'de yanlış pozitif FDG nedenleri arasında en sık görülenlerdir (1-5). Tüberküloz, akciğer kanseri dâhil olmak üzere birçok hastalığı ve bunlara ait olan radyolojik bulguları taklit edebilmektedir. Akciğer parankiminde konsolidasyon, atelektazi ve kavitasyon, lenfadenopati, plevral effüzyon tüberkülozda sık rastlanan radyolojik bulgulardır (6,7). Tüberkülozda ekstrapulmoner tutulum en sık lenf nodu, plevra, kemik ve eklemlerde görülmektedir. Günümüzde giderek artan immün süprese hastalarda daha sık görülen ekstrapulmoner tüberküloz, tüm tüberküloz olgularının yaklaşık %15'ini oluşturmaktadır. Erişkinlerde tüberküloz lenfadenit genellikle servikal bölgede bazen de supraklaviküler bölgede bir veya daha fazla sayıda ağrısız lenf nodu olarak karşımıza çıkmaktadır (4). Ayrıca erişkinlerde primer tüberkülozun bir bulgusunun da hiler veya mediastinal lenfadenopati olabileceği göz ardı edilmemelidir. Lenfadenopatiler tipik olarak sağ paratrakeal, hiler bölgede, daha az sıklıkla subkarinal ve aortikopulmoner pencerede görülür. Torasik yerleşimli lenfadenopatilerin tespitinde bilgisayarlı tomografi en duyarlı yöntemdir. Kontraslı toraks BT'de; çapı 1 cm'den büyük, cidarı kontrast madde tutan ve ortası hipodens lenf nodları tüberküloz lenfadenitin en karakteristik bulgusudur. Tanı koymak için ileri radyolojik incelemelere ve genellikle invazif girişimlere (bronkoskopi, EBUS, mediastinoskopi) gerek duyulmaktadır (4-7).

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Sarkoidoz nedeni bilinmeyen, sistemik ve granülomatöz bir hastalıktır. Tipik olarak akciğer parankimini ve hiler lenf nodlarını tutar. Tutulan diğer organlar ise deri, göz, tükrük bezleri, dalak, karaciğer ve iskelet kaslarıdır. Sıklıkla 20-40 yaş arasında görülür. Hiçbir şikâyeti olmayan bir hastada rastlantısal çekilen akciğer grafisinde saptanabileceği gibi tutulan organ sistemine ait belirtilerle de ortaya çıkabilir. Sarkoidozda en sık tutulan organ akciğerlerdir. Hastalar asemptomatik olabildikleri gibi nefes darlığı, öksürük, halsizlik ve göğüs ağrısı en sık rastlanan semptomlardır. Akciğer grafisine göre radyolojik evreleme yapılmaktadır ve bilateral hiler LAP en sık radyolojik bulgu olup sıklıkla parankimal infiltrasyonlar ve sağ paratrakeal LAP eşlik eder. Hastalığın tanısında ve takibinde akciğer radyografisi ve toraks BT önemlidir (1,8). Sarkoidoz tanısı için klinik tablo yanında histopatolojik olarak kazeifikasyon nekrozu içermeyen granülomların gösterilmesi gereklidir. Multisistem bir hastalık olmasından dolayı sistemik değerlendirme önemlidir. Tutulum olan her organdan biyopsi yapılabilir. Hastaların yaklaşık %65-70'i kendiliğinden ya da steroid tedavisi ile iyileşir (1). Pozitron Emisyon Tomografisi, pozitron yayan radyoaktif ajanlar ile işaretli maddelerin vücuda verilerek, kameralar aracılığıyla vücuttaki dağılımlarının incelendiği bir görüntüleme yöntemidir. PET ile lezyonun bulunduğu bölgedeki SUDmaks değerinin 2,5'tan yüksek olması akciğer ve mediastinal lezyonların malignite olasılığını güçlendirmektedir (9,10). Granülomatöz hastalıklar başta olmak üzere nötrofil, lenfosit ve makrofaj gibi aktif inflamatuvar hücrelerin rol aldığı infeksiyonlar ve inflamasyonlar PET-BT’de potansiyel yanlış pozitiflik sebebidir. En sık yanlış pozitiflik nedenleri olarak; tüberküloz, sarkoidoz, koksoidomikoz, aspergilloz, organize pnömoni ve vaskülitler bildirilmektedir (9). Granülomatöz hastalıkların endemik olduğu bölgelerde yaşayan hastalarda akciğer ve mediastinal lezyonların malignite riskini değerlendirmek için yapılan meta-analitik çalışmalarda PET-BT’de FDG tutulumunun değişken olduğu bildirilmektedir. Duyarlılık ve özgüllük sırasıyla %87 ve %82 olduğu rapor edilmiştir (4-7). Literatürde akciğer parankim lezyonlarına yönelik PET-BT'nin spesifitesini bildiren birçok çalışma bulunmasına rağmen, mediastinal lezyonlarla ilgili fazla çalışma bulunmamaktadır. Sunduğumuz makaledeki üç olgumuzda özellikle mediastinal lenf nodlarında yoğun FDG tutulumu mevcut olup ön tanıda malignite düşünülmüştür. Sebro ve ark (11) granülomatöz hastalıklar için endemik olan bir bölge olan Kuzey Kaliforniya'da akciğer parankim lezyonlarına yönelik yaptıkları çalışmalarında; PET-

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PET-BT'de Yüksek Düzeyde FDG Tutulumu Olan Mediastinal Lenfadenopatilerde Granülamatöz Hastalıklar Düşünülmelidir | Çelik ve ark.

BT'deki doğruluk, sensitivite, spesifite, negatif doğruluk ve pozitif doğruluk oranlarını sırasıyla %87,5, %95,1, %45,5, %62,5 ve %90,6 olarak bildirmişlerdir. Huang ve ark (10) granülomatöz hastalıklar için endemik olan bölgede yaptıkları çalışmalarında soliter akciğer lezyonu olan hastalarda geç dönemde alınan PET BT görüntülerinin malign-benign ayrımında daha duyarlı olduğunu bildirmektedirler. Zeng ve ark (12) akciğer tüberkülozu tanısı olan hastalarda yaptıkları çalışmalarında; olguların %44'ünde FDG (+) hiler ve/veya mediastinal lenfadenopati, %20'sinde yüksek FDG tutulumu olan akciğer parankim lezyonları tespit etmişlerdir. Bu durum akciğer kanseri ve diğer kanserlerin ayırıcı tanısını daha komplike hale getirmektedir. Özellikle de granülomatöz hastalıkların endemik olduğu bölgelerde bu olgulara ihtiyatlı yaklaşılması gereklidir. Malignite ayırıcı tanısında daha tümör spesifik radyofarmasötik ajanların geliştirilmeye ihtiyacı vardır. Kesin tanı için doku biyopsisinin gerekli olduğu unutulmamalıdır. Malign lezyonların benign olanlardan ayırt edilmesinde kullanılabilen Dual faz FDG PET-BT görüntülemenin malign-tüberküloz lezyonlarının ayrıcı tanısında yetersiz olduğu bildirilmektedir (3). Yeni bir radyofarmasötik olan 11C-choline özellikle akciğer parankim lezyonunun 1,5 cm üzerinde olduğu olgularda 18F-FDG ile karşılaştırıldığı çalışmalar vardır. Bu çalışmalardan birisinde akciğer kanserli hastalarda hem 18F-FDG hem 11C-choline yüksek tutulum izlenirken, tüberkülozlu hastalarda 18FFDG yüksek, 11C-choline düşük tutulum göstermiştir (13). Ayrıca sarkoidozis için Godalinium ile yapılan manyetik rezonans görüntülemede hastalığın aktif olduğu bölgeler saptanarak biyopsi için en uygun yer belirlenmeye çalışılmaktadır (2). Olgularımızda mediyastinal lezyonların FDG SUDmaks değerleri 4,36 ila 28,7 arasında değişmektedir. Malignite ön tanısı yüksek olan bu olgulardan bir tanesinde daha önce üç farklı malignite nedeniyle tedavi görmüş olması da ayırıcı tanıyı daha da zorlaştırmaktadır. Bazı lezyonların LAP olması, bazılarının konglomere kitle halinde olması ve hatta beraberinde akciğer parankimin lezyonlarının olması invazif bir girişimi kaçınılmaz hale getirmektedir. Mediastinal lezyonların ve LAP'ların tanısında en sık mediastinoskopi, transkarinal ya da transbronşiyal bronkoskopik biyopsi, EBUS ve EUS kullanılmaktadır. Servikal videomediastinoskopi halen altın standart yöntemdir. Kliniğimizde servikal videomediastinoskopi mediastinal lezyonların tanısında oldukça sık kullanılmaktadır. Sonuç olarak; PET-BT'de lenf nodlarında yüksek FDG tutulumu olan olgularda, malignite anamnezi olsa da

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özellikle atipik lokalizasyonlu lenf nodlarının ön planda olduğu olgularda kesin tanı ve tedavi için doku biyopsisi gerekmektedir. Tüberküloz, radyolojik olarak birçok hastalığı taklit edebildiği için ülkemizde her türlü klinik ve radyolojik görünümde tüberküloz ve diğer granülomatöz hastalıklar ön tanılar arasında düşünülmelidir.

ÇIKAR ÇATIŞMASI Bu makalede herhangi bir çıkar çatışması bildirilmemiştir.

YAZAR KATKILARI Fikir - B.Ç., M.A.Y., M.G.P., M.Ş.; Tasarım ve Dizayn B.Ç., M.A.Y., M.G.P., M.Ş.; Denetleme - B.Ç., M.A.Y., M.G.P., M.Ş.; Kaynaklar - B.Ç., M.G.P.; Malzemeler B.Ç., M.Ş.; Veri Toplama ve/veya İşleme - B.Ç., M.Ş.; Analiz ve/veya Yorum - M.Ş., B.Ç.; Literatür Taraması B.Ç., M.Ş.; Yazıyı Yazan - B.Ç., M.Ş.; Eleştirel İnceleme B.Ç., M.Ş., M.A.Y., M.G.P.

KAYNAKLAR 1.

Carmona EM, Kalra S, Ryu JH. Pulmonary sarcoidosis: diagnosis and treatment. Mayo Clin Proc 2016; 91:94654. [CrossRef]

2.

Mana J. Magnetic resonance imaging and nuclear imaging in sarcoidosis. Curr Opin Pulm Med 2002; 8:45763. [CrossRef]

3.

Treglia G, Taralli S, Calcagni ML, Maggi F, Giordano A, Bonomo L. Is there a role for fluorine 18 fluorodeoxyglucose-positron emission tomography and positron emission tomography/computed tomography in evaluating patients with mycobacteriosis? A systematic review. J Comput Assist Tomogr 2011; 35:387-93. [CrossRef]

4.

Demirkazık FB. Akciğer tüberkülozu radyolojisi. In: Tüberküloz. Özkara Ş, Kılıçarslan Z, eds. Toraks Kitapları. AVES Yayıncılık, İstanbul, 2010, 181-205. [CrossRef]

5.

du Toit R, Shaw JA, Irusen EM, von Groote-Bidlingmaier F, Warwick JM, Koegelenberg CF. The diagnostic accuracy of integrated positron emission tomography/computed tomography in the evaluation of pulmonary mass lesions in a tuberculosis-endemic area. S Afr Med J 2015; 105:1049-52. [CrossRef]

6.

Mamede M, Higashi T, Kitaichi M, Ishizu K, Ishimori T, Nakamoto Y, et al. [18F]FDG uptake and PCNA, Glut-1, and Hexokinase-II expressions in cancer and inflammatory lesions of the lung. Neoplasia 2005; 7:369–79. [CrossRef]

7.

Rosenbaum SJ, Lind T, Antoch G, Bockisch A. FalsePositive FDG PET uptake−the role of PET/CT. Eur Radiol 2006; 16:1054–65. [CrossRef] www.respircase.com


Respiratory Case Reports

8.

Braun JJ, Kessler R, Constantinesco A, Imperiale A. 18FFDG PET/CT in sarcoidosis management: review and report of 20 cases. Eur J Nucl Med Imaging 2008; 35:1537-43. [CrossRef]

11. Sebro R, Aparici CM, Hernandez-Pampaloni M. FDG PET/CT evaluation of pathologically proven pulmonary lesions in an area of high endemic granulomatous disease. Ann Nucl Med 2013; 27:400–5. [CrossRef]

9.

Ko JP, Ponzo F, Vlahos I. Diseases of the Lungs and Pleura: FDG PET/CT. In: Kramer EL, Ko JP, Ponzo F, Mourtzikos K; eds. Positron Emission Tomography Computed Tomography. A Disease-Oriented Approach. New York: Informa Healthcare, 2008:127-227.

12. Zheng Z, Pan Y, Guo F, Wei H, Wu S, Pan T, et al. Multimodality FDG PET/CT appearance of pulmonary tuberculoma mimicking lung cancer and pathologic correlation in a tuberculosis-endemic country. South Med J 2011; 104:440-5. [CrossRef]

10. Huang YE, Huang YJ, Ko M, Hsu CC, Chen CF. Dualtime-point 18F-FDG PET/CT in the diagnosis of solitary pulmonary lesions in a region with endemic granulomatous diseases. Ann Nuc Med 2016; 30:652-8. [CrossRef]

13. Hara T, Kosaka N, Suzuki T, Kudo K, Niino H. Uptake rates of 18F-fluorodeoxyglucose and 11C-choline in lung cancer and pulmonary tuberculosis: a positron emission tomography study. Chest 2003; 124:893-901. [CrossRef]

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Respir Case Rep 2017;6(2):96-98 DOI: 10.5505/respircase.2017.92499

OLGU SUNUMU

CASE REPORT

Maybe it is More than Pneumonia: Case Report of an Intralobar Sequestration in a 20-Year-Old Male Pnömoni Pnömoniden de Fazlası Olabilir: Yirmi Yaşında Erkek İntralober Sekestrasyon Olgusu Sunumu

RESPIRATORY CASE REPORTS

Eric Paul Borrelli

Abstract

Özet

Pulmonary sequestration (PS) is rare congenital lung malformation typically diagnosed with fetal ultrasound or computed tomography scans. Potential complications of PS include recurrent respiratory infections, hemorrhage, heart failure, and respiratory distress. Recommended treatment is surgical resection. Presently described is case of a 20-year-old male diagnosed with intralobar PS.

Pulmoner sekestrasyonlar (PS) nadir görülen konjenital malformasyonlar olup çocuklarda fetal ultrason ve erişkinlerde bilgisayarlı tomografi ile tipik olarak tanı almaktadırlar. PS’nin potansiyel komplikasyonları tekrarlayan solunum yolu infeksiyonları, hemoraji, kalp yetmezliği ve solunumsal yetmezliklerdir. Önerilen tedavi cerrahi rezeksiyondur. Bu makalede intralober PS tanısı konmuş 20 yaşında erkek olgu tartışıldı.

Key words: Congenital Malformations, Infections, Pneumonia, Epidemiology, Pulmonary Sequestration.

Pulmonary sequestration (PS) is rare, amounting to 0.15% to 6.4% of all congenital pulmonary malformations (1). Pulmonary sequestration involves nonfunctional, not fully developed lung tissue. Sequestration typically receives blood supply from systemic circulation, rather than the pulmonary arteries, and specifically from the thoracic aorta (74%) (1,2). Venous blood return from PS is usually from the pulmonary veins, although occasionally venous return is through systemic circulation (1,2). In addition, PS is separated from the bronchial system (3). There are 2 types of sequestration: intralobar and extralobar. Intralobar sequestration University of Rhode Island College of Pharmacy, Kingston, Rhode Island, United States

Anahtar Sözcükler: Konjenital malformasyonlar, enfeksiyon, pnömoni, epidemiyoloji, pulmoner sekestrasyonterapi.

is contained within same pleural lining as the lobe in which it occurs (2). Extralobar sequestrations are contained within their own pleura (2). Intralobar sequestrations make up 75% to 85% of all PSs (4). PS is typically diagnosed with fetal ultrasound or computed tomography (CT) scans. Most common symptoms of sequestration are cough, recurrent pneumonia, and expectoration (1). Potential complications of PS include recurrent pulmonary infections, hemorrhage, respiratory distress, and heart failure (3,4). Recommended treatment option is usually surgical resection to remove the sequestration (5). Rhode Island Üniversitesi, Farmakoloji Fakültesi, Kingston, Rhode Island, ABD

Submitted (Başvuru tarihi): 31.12.2016 Accepted (Kabul tarihi): 08.02.2017 Correspondence (İletişim): Eric Paul Borrelli, University of Rhode Island College of Pharmacy, Kingston, Rhode Island, United States e-mail: ericborrelli@my.uri.edu

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Respiratory Case Reports

CASE A 20-year-old male went to his primary care physician for physical examination and complained of chest pressure and discomfort on left side. He stated that sometimes the pressure radiated down his left arm and had been ongoing for about a month. He described pressure as being constant throughout the day, with no changes due to exertion, lying down, or exercise. The patient had no history of cough or shortness of breath. He had previously been in good health and had no history of smoking. Electrocardiogram (ECG) was performed and the results were normal. His blood pressure was 110/80 mm Hg, and his pulse was 80 bpm and regular. Laboratory values were normal except for positive mycoplasma immunoglobulin M (IgM) and equivocal mycoplasma immunoglobulin G (IgG). Purified protein derivative skin test was performed and results were negative. Chest X-ray was performed. Left lung was clear; however, right lung indicated reticulonodular haziness at the base on frontal view. Impression was suspicious of developing right lower lobe infiltrate. Initial diagnosis was mycoplasma pneumonia. The patient had mycoplasma pneumonia twice previously, at 8 years of age and again at 9 years of age. He was prescribed clarithromycin 500mg twice daily with blood work to be repeated in 2 weeks. Laboratory values showed mycoplasma IgM was still positive and mycoplasma IgG was still equivocal. Symptoms were still present. Clarithromycin treatment was extended for 2 more weeks. The patient was seen for 2 follow-up appointments within the next 4 weeks with symptoms continuing and positive mycoplasma IgG and mycoplasma IgM values. Second chest X-ray was performed. Left lung remained clear. Right lung showed persistent haziness in the right medial and posterior lung base and was suspicious for pneumonia. There was also mild pulmonary hyperinflation and mild peribronchial thickening. Chest CT scan with contrast was performed. CT scan revealed superimposed infection. It also indicated right lower lobe opacity medially with apparent dilated bronchus which appeared separated from main segment bronchi and was suspicious of congenital abnormality of either lung sequestration or congenital pulmonary airway malformation. Consultation appointment was made with a pulmonologist. Pulmonologist performed physical exam and found normal lung sounds. The pulmonologist interpreted CT scan to be PS. CT angiography chest scan was performed and revealed dilated bronchus separated from the main segment bronchi (Figure 1). Findings were most consistent with intralobar PS. Arterial supply of sequestraCilt - Vol. 6 SayÄą - No. 2

tion was aberrant branch of the descending thoracic aorta (Figure 2). Venous return was from branch of the lower lobe pulmonary vein. There were small areas of glass opacity in the right lower lobe suspicious of infection. After follow-up with the pulmonologist, surgical removal of sequestration was planned. The patient was scheduled for video-assisted thoracic surgery (VATS) 4 months later. Right lower lobe wedge resection via VATS to remove PS was performed without complication. The patient was discharged from hospital the next morning and no complications or pain were reported in follow-up with the surgeon 2 weeks later. The patient no longer experienced chest pain or pressure on his left side. Follow-up with pulmonologist 6 months later revealed no complications and no chest pain or pressure since the surgery.

Figure 1: Computed tomography (CT) angiography of the chest with the arrow pointing to the intralobar sequestration

Figure 2: Computed tomography (CT) angiography of the chest with the arrow pointing to the feeding vessel of the sequestration stemming of the descending thoracic aorta

DISCUSSION This patient had classic symptoms of PS. He had recurrent pneumonia, having mycoplasma pneumonia 3 times in his life, with latest occurrence not responding to antibiot-

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Maybe it is More than Pneumonia: Case Report of an Intralobar Sequestration in a 20-Year-Old Male | Borrelli et al.

ics. PS was discovered due to constant non-identifiable chest pain and pressure that radiated down his left arm. There is case report of an 18-year-old male who had intralobar sequestration of the lower left lobe, yet experienced chest pain on his right side radiating down his right arm (2). There may be a previously unrecognized correlation between PS and chest pain. Based on location and type of pain described, it is consistent with neuropathic pain. The present patient reported not experiencing pain or pressure after surgery to remove sequestration. Therefore, it is plausible that in both of these cases, PS was affecting phrenic nerve, which led to continuous radiating pain. PS in currently described patient had typical features: It received blood supply via systemic circulation from the thoracic aorta and venous return was through the pulmonary veins. This patient’s PS was intralobar, which is consistent with most PS cases (75% to 85%) (4). Intralobar sequestration is contained within the same visceral pleura of the adjacent lobe. Extralobar sequestration is contained within its own visceral pleura and is separate from the lung (2,6). Intralobar sequestration is most commonly in lower lobe of the lung, and nearly 67% are in the left lung (4). Surgical resection is recommended treatment for PS. Most common surgical techniques are either thoracotomy or VATS (7). Wedge resection may be sufficient to remove PS, but if severely infected or difficult to resect, lobectomy may be required (7,8). In this patient, VATS was recommended to minimize complications to surgery and shorten recovery time. PS in this patient was removed via wedge resection and lobectomy was not necessary.

AUTHOR CONTRIBUTIONS Concept - E.P.B.; Planning and Design - E.P.B.; Supervision - E.P.B.; Funding - E.P.B.; Materials - E.P.B.; Data Collection and/or Processing - E.P.B.; Analysis and/or Interpretation - E.P.B.; Literature Review - E.P.B.; Writing E.P.B.; Critical Review - E.P.B.

YAZAR KATKILARI Fikir - E.P.B.; Tasarım ve Dizayn - E.P.B.; Denetleme E.P.B.; Kaynaklar - E.P.B.; Malzemeler - E.P.B.; Veri Toplama ve/veya İşleme - E.P.B.; Analiz ve/veya Yorum E.P.B.; Literatür Taraması - E.P.B.; Yazıyı Yazan - E.P.B.; Eleştirel İnceleme - E.P.B.

REFERENCES 1.

Savic B, Birtel FJ, Tholen W, Funke HD, Knoche R. Lung sequestration: report of seven cases and review of 540 published cases. Thorax 1979; 34:96-101. [CrossRef]

2.

Hertzenberg C, Daon E, Kramer J. Intralobar pulmonary sequestration in adults: three case reports. J Thorac Dis 2012; 4:516-9. [CrossRef]

3.

Van Raemdonck D, De Boeck K, Devlieger H, Demedts M, Moerman P, Coosemans W, et al. Pulmonary sequestration: a comparison between pediatric and adult patients. Eur J Cardiothorac Surg 2001; 19:388–95.

4.

Wani SA, Mufti GN, Bhat NA, Baba AA. Pulmonary Sequestration: Early Diagnosis and Management. Case Rep Pediatr 2015; 2015:454860. [CrossRef]

5.

Litt D, Gandhi S, Bhinder S, Blitz M, McIntyre K. Incidental finding and management of intralobar sequestration of the lung in a 24-year-old man. Can Respir J 2013; 20:403-5. [CrossRef]

6.

Qian X, Sun Y, Liu D, Wu X, Wang Z, Tang Y. Pulmonary sequestration: a case report and literature review. Int J Clin Exp Med 2015; 8:21822-5.

7.

Brown SC, De Laat M, Proesmans M, De Boeck K, Van Raemdonck D, Louw J, et al. Treatment strategies for pulmonary sequestration in childhood: resection, embolization, observation? Acta Cardiol 2012; 67:629-34.

8.

Sun X, Xiao Y. Pulmonary sequestration in adult patients: a retrospective study. Eur J Cardiothorac Surg 2015; 48:279-82. [CrossRef]

CONCLUSION Pulmonary sequestration is typically diagnosed with fetal ultrasound or chest CT scan. Early diagnosis is key to prevent potentially life-threatening complications. Surgical resection is currently primary treatment option to prevent complications.

CONFLICTS OF INTEREST None declared.

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Respir Case Rep 2017;6(2):99-102 DOI: 10.5505/respircase.2017.94834

OLGU SUNUMU

CASE REPORT

Pulmonary Nodule-associated Cat Scratch Disease in an Immunocompromised Patient Bağışıklığı Baskılanmış Hastada Kedi Tırmığına Bağlı Pulmoner Nodul

RESPIRATORY CASE REPORTS

Levent Özdemir1, Burcu Özdemir2, Mehtap Şencan3, Suat Durkaya4, Ayşegül Kaynar5, Zulal Özbolat1, Sema Çalışkan2, Ali Ersoy6

Abstract

Özet

Cat-scratch disease (CSD) is an infectious disease, presenting with chronic inflammation of lymph nodes that drain the portal of entry of the causative organism in immunocompetent persons. It may also manifest as encephalitis, neuroretinitis, granulomatous conjunctivitis, hepatosplenic involvement, or pneumonia and thrombocytopenic purpura in immunocompromised patients. A 50-year-old, previously healthy woman was evaluated for symptoms of cough, fever, and arthralgia. She had history of surgery for hydatid cyst (liver) 4 years earlier and 1 year of Deltacortril use for rheumatoid arthritis. Nodular formations were observed in the right anterior upper lobe, right middle lobe, and right inferior posterobasal lobe on chest tomography image. Laboratory analysis revealed no abnormal findings except leukocytosis. Aerobic culture and EZN staining of sputum were negative. The patient underwent diagnostic video-assisted thoracoscopic surgery. Pathological results were reported as granulomatous disease, excluding tuberculosis and sarcoidosis, and indicating likely CSD, presenting with polymorphonuclear leukocytes in the granulomas.

Kedi tırmığı hastalığı, bağışıklık sistemi normal kişilerde, giriş yerinin drene olduğu lenf düğümlerinde kronik inflamasyonla seyreden bir infeksiyondur. Bağışıklık sistem baskılanmış olan hastalarda ensefalit, nöroretinit, granülomatöz konjunktivit, hepatosplenik tutulum, pnömoni ve trombositopenik purpura gibi klinik tablolar şeklinde de ortaya çıkabilir. Elli yaşında kadın hasta öksürük, ateş, eklem ağrısı nedeni ile değerlendirildi. Özgeçmişinde dört yıl önce karaciğer kist hidatiği nedeni ile operasyon ve romatoid artrit nedeni ile bir yıldır deltakortil kullanımı mevcuttu. Toraks tomografisinde sağ alt lob superiyor ve üst lobta nodul saptandı. Laboratuvar incelemesinde lökositoz dışında anormallik saptanmadı. Balgam aerob kültür ve ARB incelemesi negatif olarak saptandı. Hastaya tanısal VATS uygulandı. Patoloji sonucu granülomlar içinde polimorf nüveli lokositler, tbc ve sarkoidoz dışı granülomatöz hastalık ön planda kedi tırmığı hastalığı olarak raporlandı. Anahtar Sözcükler: Pulmoner nodul, Kedi tırmığı, bağışıklık baskılanmış.

Key words: Pulmonary nodule, Cat Scratch Disease, immunocompromised.

1

Department of Chest Diseases, Dörtyol State Hospital, Hatay, Turkey 2 Department of Chest Diseases, İskenderun State Hospital, Hatay, Turkey 3 Department of Infection Diseases, Dörtyol State Hospital, Hatay, Turkey 4 Department of Thorasic Surgey, İskenderun State Hospital, Hatay, Turkey 5 Department of Pathology, İskenderun State Hospital, Hatay, Turkey 6 Department of Chest Diseases, Antakya State Hospital, Hatay, Turkey

1

Dörtyol Devlet Hastanesi, Göğüs Hastalıkları Kliniği, Hatay İskenderun Devlet Hastanesi, Göğüs Hastalıkları Kliniği, Hatay 3 Dörtyol Devlet Hastanesi, İnfeksiyon Hastalıkları Kliniği, Hatay 4 İskenderun Devlet Hastanesi Göğüs Cerrahisi Kliniği, Hatay 5 İskenderun Devlet Hastanesi, Patoloji Bölümü, Hatay 6 Antakya Devlet Hastanesi, Göğüs Hastalıkları Kliniği, Hatay 2

Submitted (Başvuru tarihi): 13.08.2016 Accepted (Kabul tarihi): 12.12.2016 Correspondence (İletişim): Levent Özdemir, Department of Chest Diseases, Dörtyol State Hospital, Hatay, Turkey e-mail: levent2408@mynet.com

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Respiratory Case Reports

Cat-scratch disease (CSD) is an infectious illness caused by Gram-negative rod Bartonella henselae and accompanied by chronic inflammation, including frequently slowly progressive and sometimes chronic form of regional lymphadenitis near the wound site (1). Disease can occur with wide spectrum of presentation, including osteomyelitis, encephalitis, neuroretinitis, granulomatous conjunctivitis, hepatosplenic micro abscesses, and renal abscesses in immunocompromised patients (2). Pulmonary manifestations are rare. Usual pulmonary manifestation is pleural effusion and pneumonia in immunocompromised host. Pulmonary nodules are rarely seen in patients with bacillary angiomatosis (3,4). In this article, patient presenting with pulmonary nodules who was under immunosuppressive medication and diagnosed with CSD via video-assisted thoracoscopic surgery (VATS) is described.

it was determined that 17 cats lived in her house and that she was occasionally clawed by them. The patient received doxycycline 200 mg/d for 4 weeks after VATS based on histopathological findings. After treatment, the patient was discharged from the hospital without complication. Written consent to publication was obtained from the patient at discharge.

CASE A 50-year-old, previously healthy woman presented with 8-day history of fever (38-40°C), non-productive cough, and arthralgia. She had history of surgery for hydatid cyst (liver) 4 years earlier and 1 year of prednisone use (initial dose: 20 mg/d, maintenance dose: 5 mg/d) for rheumatoid arthritis. On physical examination, she was febrile (38.7°C); tachycardic, with heart rate of 108 bpm; and respiratory rate of 22 breaths per minute. Bilateral rhonchi during expirium were present on chest auscultation. No pathological laboratory findings except leukocytosis (14,000/mm3; neutrophil count: 10,900/mm3) and elevated C-reactive protein level of 58 mg/dL were found. Serum serology for HIV was negative. Both sputum culture and aerobic blood culture revealed negative results. Ziehl-Neelsen staining of sputum was negative for acidfast bacilli. Chest computed tomography (CT) (Figure 1a and b) revealed nodular formations surrounded by ground-glass opacities in the right anterior upper lobe, right middle lobe, and right inferior posterobasal lobe. Ampicillin/sulbactam 4x1.5 gr/d, clarithromycin 2x500 mg/d were initiated for non-specific treatment of nodular formations. As radiographical chest findings did not regress and diagnosis could not be made from culture results, diagnostic VATS was performed for differential diagnosis of sarcoidosis, tuberculosis, rheumatoid nodule, and hydatid cyst. Histopathological examination revealed polymorphonuclear leukocytes in the granulomas (Figure 2), indicating granulomatous disease, excluding tuberculosis and sarcoidosis, and suggesting CSD. After the patient was questioned again regarding her medical history, Cilt - Vol. 6 Sayı - No. 2

Figure 1a and b: Chest computed tomography revealed nodular formations surrounded by ground-glass opacities in the right anterior upper lobe, right middle lobe, and right inferior posterobasal lobe

Figure 2: Histopathological examination demonstrated polymorphonuclear leukocytes in the granulomas

DISCUSSION Despite many published articles on CSD with systemic dissemination, there have been only a few cases presenting with pulmonary nodules in immunocompromised patients in literature (3-6). Our patient was immunosup-

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Pulmonary Nodule-associated Cat Scratch Disease in an Immunocompromised Patient | Özdemir et al.

pressed due to steroid therapy for rheumatoid arthritis and is a rare case of CSD presenting as lung nodules. CSD exists in 2 forms: typical and atypical. In typical form, an initial skin lesion like non-painful, erythematous papule or pustule of 2 to 10 mm in diameter develops within 3 to 12 days at the site of scratch or bite, and often heals within 2 to 4 weeks without scarring. Subsequent development of regional lymphadenitis is most important clinical manifestation. Symptoms of low-grade fever, chill, weakness, anorexia, nausea, and headache may be present. In immunocompetent patients, CSD heals spontaneously in 2 to 5 months, and only rarely with scarring. However, disseminated lymphadenitis and fatal clinical outcomes may occur in immunocompromised patients, including those with AIDS, malignancy, or using immunosuppressive medication. In recent years, atypical form of CSD was reported in 10% to 25% of patients who had contact with the etiological agent. This form can present with high-grade fever, Parinaud’s oculoglandular syndrome (5-6%), neuroretinitis, endocarditis, encephalitis, arthralgia, arthritis, synovitis, osteomyelitis (0-3%), pneumonia (0-2%), or granulomatous hepatitis. Whereas our patient, who had regular contact with cats, manifested with clinical findings of fever, cough, and arthralgia, no regional lymphadenitis was observed on physical examination (7). Serological tests are accepted as criterion standard in diagnosis of CSD. Initiation of humoral immune response begins before or simultaneously with onset of symptoms; therefore, estimation of single high titer of IgM and IgG antibodies by indirect fluorescent antibody or enzyme immunoassay is thought to be sufficient for diagnosis. Value of other diagnostic tests, including polymerase chain reaction and bacterial culture, is limited (8). Serological tests are not routinely used in our country for diagnosis of CSD (9). Typical findings are estimated from histopathological examination of involved regional lymphadenitis. These findings include lymphoid hyperplasia accompanied by arteriolar proliferation initially, and subsequent regions of necrotizing granuloma involving histiocytes and polymorphonuclear leukocytes (10). Diagnosis of our case was made via clinical history and histopathological demonstration of polymorphonuclear leukocytes in the granulomas. CSD restricts itself. Antibiotherapy is generally not necessary except in disseminated CSD (11). Disseminated CSD is more frequent in immunocompromised patients. Longterm antibiotic therapy is required to reduce mortality and

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morbidity in immunocompromised patients with atypical clinical course (12). Azithromycin, clarithromycin, doxycycline, trimethoprim-sulfamethoxazole, rifampicin, ciprofloxacin, and gentamycin are used in treatment of CSD (13). We used ampicillin-sulbactam and clarithromycin in initial treatment. There was no response to that therapy; however after pathological diagnosis, doxycycline was administered for 4 weeks due to immunodeficiency. As a conclusion, clinicians should be aware that CSD may manifest on occasion as pulmonary nodule in immunocompromised patients.

CONFLICTS OF INTEREST None declared.

AUTHOR CONTRIBUTIONS Concept - L.Ö., B.Ö., M.Ş., S.D., A.K., Z.Ö., S.Ç., A.E.; Planning and Design - L.Ö., B.Ö., M.Ş., S.D., A.K., Z.Ö., S.Ç., A.E.; Supervision - L.Ö., B.Ö., M.Ş., S.D., A.K., Z.Ö., S.Ç., A.E.; Funding - L.Ö., B.Ö.; Materials - L.Ö., B.Ö.; Data Collection and/or Processing - L.Ö., B.Ö.; Analysis and/or Interpretation - L.Ö., B.Ö.; Literature Review - L.Ö., B.Ö.; Writing - L.Ö., B.Ö., M.Ş.; Critical Review - L.Ö.

YAZAR KATKILARI Fikir - L.Ö., B.Ö., M.Ş., S.D., A.K., Z.Ö., S.Ç., A.E.; Tasarım ve Dizayn - L.Ö., B.Ö., M.Ş., S.D., A.K., Z.Ö., S.Ç., A.E.; Denetleme - L.Ö., B.Ö., M.Ş., S.D., A.K., Z.Ö., S.Ç., A.E.; Kaynaklar - L.Ö., B.Ö.; Malzemeler L.Ö., B.Ö.; Veri Toplama ve/veya İşleme - L.Ö., B.Ö.; Analiz ve/veya Yorum - L.Ö., B.Ö.; Literatür Taraması L.Ö., B.Ö.; Yazıyı Yazan - L.Ö., B.Ö., M.Ş.; Eleştirel İnceleme - L.Ö.

REFERENCES 1.

Centers for Disease Control and Prevention (CDC). Catscratch disease in children-Texas, September 2000August 2001. MMWR Morb Mortal Wkly Rep 2002; 51:212-4.

2.

Maguina C, Gotuzzo E. Bartonellosis. New and old. Infect Dis Clin North Am 2000; 14:1-22. [CrossRef]

3.

Dutta A, Schwarzwald HL, Edwards MS. Disseminated bartonellosis presenting as neuroretinitis in a young adult with human immunodeficiency virus infection. Pediatr Infect Dis J. 2010; 29:675–7. [CrossRef]

4.

Moore EH, Russell LA, Klein JS, White CS, McGuinness G, Davis LG, et al. Bacillary angiomatosis in patients with

www.respircase.com


Respiratory Case Reports

AIDS: multiorgan imaging findings. Radiology 1995; 197:67–72. [CrossRef] 5.

6.

Burrowesn P, Goodman p. Multiple pulmonary nodules as a manifestation of cat-scratch disease. Can Assoc Radiol J 1995; 46:48-50. Bandyopadhyay A, Burrage LC, Gonzalez BE. Pulmonary nodules in an immunocompetent child with cat scratch disease. Pediatr Infect Dis J 2013; 32:1390-2. [CrossRef]

7.

Celebi B. Bortanella Henselae and its infections. Mikobiyol Bül 2008; 42:163-175.

8.

Sander A, Berner R, Ruess M. Serodiagnosis of cat scratch disease; response to Bartonella henselae in children and a review of diagnostic methods. Eur J Clin Microbiol Infect Dis 2001; 20:392-401. [CrossRef]

Cilt - Vol. 6 Sayı - No. 2

9.

Doğanay M, Yıldız O. Deri ve derialtı dokusunun bakteriyel enfeksiyonları. In: Wilke Topcu A, Soyletir G, Doğanay M (eds). Enfeksiyon Hastalıkları ve Mikrobiyolojisi. 3. Baskı, İstanbul: Nobel Tıp Kitapevleri, 2008:1269-82.

10. Eroğlu C, Çandır N, Dervişoğlu A, Kefeli M. Kedi Tırmığı Hastalığı Olgusu. Mikobiyol Bül 2007: 41 603-6. 11. Margileth AM. Antibiotic therapy for cat-scratch disease: clinical study for therapeutic outcome in 268 patients and a review of the literature. Pediatr Infect Dis J 1992; 11:474-8. [CrossRef] 12. Spach DH, Koehler JE. Bartonella-associated infections. Infect Dis Clin North Am 1998; 12:137-55. [CrossRef] 13. Batts S, Demers DM. Spectrum and treatment of catscratch disease. Pediatr Infect Dis J 2004; 23:1161-2.

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Respir Case Rep 2017;6(2):103-106 DOI: 10.5505/respircase.2017.38981

OLGU SUNUMU

CASE REPORT

Vertebral Hydatid Disease: White Cancer Vertebral Kist Hidatik: Beyaz Kanser

RESPIRATORY CASE REPORTS

Mustafa Çalık1, Saniye Göknil Çalık2, Hıdır Esme1

Abstract

Özet

Hydatid disease (HD), or echinococcosis, is a complex, chronic, neglected zoonotic disease caused by cestodes of the genus Echinococcus. The infection is found worldwide affects an estimated 1.2 million people. Vertebral involvement is rare, affecting less than 1% of all HD patients, even in endemic regions. Diagnosis and treatment of osseous HD is quite challenging; it is also called “white cancer.” Despite surgical and medical treatment, recurrence ratio for HD is 40% to 100% within average of 30 months. Challenges arising from anatomical and physiological features in cycle of treatment and recurrence can be frustrating for clinicians. New methods, particularly medications that can better penetrate the central nervous system, are needed to prevent recurrence. Presently described is a case of vertebral HD penetrating the spinal canal.

Kist hidatik (KH), dünya çapında tahminen 1,2 milyon insanı etkileyen sestod Echinococcus granulosus'un neden olduğu kronik, kompleks ve ihmal edilen zoonotik bir enfeksiyondur. Vertebral tutulum endemik bölgelerde bile tüm KH hastaların %1’den daha azını etkileyen nadir bir durumdur. Tanı ve tedavisi oldukça zordur. Bu nedenle “Beyaz kanser” olarak adlandırılmıştır. Bütün cerrahi ve medikal tedavilere rağmen rekürrens oranı %40-100 arasında ve ortalama süreside 30 aydır. Bölgenin anatomik ve fizyolojik özelliklerinden kaynaklanan güçlüklerde eklenince hastaların tedavileri daha da zorlaşmaktadır. Klinisyen tedavi ve hastalık arasında kısır bir döngünün içine girmektedir. Hem cerrahi hem de medikal açıdan rekürrensi engelleyecek; kısır döngüyü kıracak yeni yöntemler ve özellikle santral sinir sistemine daha iyi penetre olan ilaçlara ihtiyaç duyulmaktadır. Burada spinal kanala uzanım gösteren Vertebral KH olgusunu sunduk.

Key words: Olağandışı lokalizasyonu, omurga, kemik, hidatik kist.

vertebra,

Hydatid disease (HD) is a complex, chronic zoonotic infection. Geographically very widespread, it affects an estimated 1.2 million people, especially in rural communities due to inadequate environmental health, preventive medicine, and veterinary services (1). There are 4 forms of the disease caused by different species of parasite. The most frequently seen in humans is E. granulosus, which is found in domestic animals, and causes cystic echinococcosis. More rarely, infection with E. multilocularis, which is found in wildlife, causes alveolar echinococcosis. E. vogeli and E. oligarthrus are

Anahtar Sözcükler: Unusual localization, vertebra, spine, bone, hydatid cyst.

underlying causes of polycystic and unicystic diseases, respectively, and are rarely seen in humans. The most frequent localizations are the liver and the lungs; however, HD may be primary or secondary anywhere in the body (2). Vertebral involvement is rare, affecting less than 1% of all HD patients, even in endemic regions (3). Diagnosis and treatment of osseous HD is quite challenging; severity and behavior led to it also being called “white cancer” (4). We hereby present a case of vertebral HD in the spinal canal.

1

Department of Thoracic Surgery, Health Sciences University, Kon- 1Sağlık Bilimleri Üniversitesi Konya Eğitim ve Araştırma Hastaya Training and Research Hospital, Konya, Turkey nesi, Göğüs Cerrahisi Kliniği, Konya 2 2 KTO Karatay University Vocational School of Health Services, KTO Karatay Üniversitesi Sağlık Hizmetleri Meslek YüksekoKonya, Turkey kulu, Konya Submitted (Başvuru tarihi): 06.06.2016 Accepted (Kabul tarihi): 21.10.2016 Correspondence (İletişim): Saniye Göknil Çalık, KTO Karatay University Vocational School of Health Services, Konya, Turkey e-mail: drgoknil@windowslive.com

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Respiratory Case Reports

CASE A 64-year-old female patient was admitted to our hospital 3 years ago with complaints of back pain and weakness and numbness in her hands and feet. No outstanding circumstances were specified in physical examination or lab tests at admission. Thorax computed tomography (CT) scan of the left lung upper lobe apicoposterior segment revealed smooth, contoured mass lesion 45 x 35 mm in size penetrating the spinal canal and causing damage at lateral fourth thoracic vertebra (T4) (Figure 1). Suspecting neurogenic tumor, histopathological confirmation and surgery were suggested; however, the patient refused any treatment or operation. The patient was admitted to emergency room of our hospital after complaints had increased over 3 years. It was reported that she was hardly walking or using her hands. At admission, she was generally in good condition, conscious, cooperative, and oriented. There was only minimal bilateral lower extremity weakness observed in physical examination. All lab test results were normal and indirect hemagglutination assay was positive for hydatid cyst. In thorax CT of the left lung upper lobe apicoposterior segment, a smooth contoured 45x35mm mass lesion was observed, penetrating into spinal canal, causing destruction at lateral T4 vertebra (Figure 2). Thoracic magnetic resonance screening revealed 40 x 37 x 35 mm, smooth, marginated, and macrolobulated mass lesion. It explicitly restricted the neural foramen at T4, extending to arcus aorta and neighboring the left lung hypointense at lateral T1 and hyperintense at T2, and having involvement of minimal homogenous contrast after intravenous gadolinium injection. The specified lesion was observed extending into the neural foramen, causing damage in vertebral body and posterior elements (Figure 3). Posterolateral thoracotomy was performed through fourth intercostal space. After accessing the thorax, cohesions were separated with obtuse and sharp dissections. Exploration yielded 4 x 3.5 x 3.5 cm, smooth, marginated, lobulated lesion, neighboring T4 lateral to the arcus aorta and the left lung. Lesion extending into spinal canal was separated from surrounding tissue and multiple germinative membranes were removed. Medulla spinalis was intact. No additional surgery was performed since the location was vertebral body. Thorax tissues were closed. No perioperative complications developed. Diagnosis was pathologically verified. The patient was discharged on ninth postoperative day without any complaint and treated with albendazole (10 mg/kg/d) for 6 months. Following operation, her complaints regressed and then were completely alleviated. Cilt - Vol. 6 SayÄą - No. 2

At 1-year follow-up, no recurrence or complications were observed.

Figure 1: Thoracic computed tomography scans of the patient (at T4 level)

Figure 2: Three-dimensional computed tomography scan showing expanding cystic mass (white arrows) at T4 level and destruction of vertebral body

Figure 3: Magnetic resonance images of the patient (at T4 level)

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Vertebral Hydatid Disease: White Cancer | Göknil Çalık et al.

DISCUSSION Understanding of the physiopathology and lifecycle of cyst has developed over the last 2 centuries, although mankind has been aware of HD for 2000 years (5). New explorations continue to reveal more about HD. In addition to the 4 well-known types, recently, Echinococcus shiquicus and Echinococcus felidis species were identified in small mammals in the Tibetan plateau and in lions in Africa, respectively. The zoonotic potential and spread have been investigated (6). Although it is primeval, HD is still an important human health problem, particularly in endemic regions of the Mediterranean basin, Eastern Europe, Middle East, Far East, Central and South America, as well as former Soviet republics. It seems it will continue to exist into the future. Humans accidentally become host outside the normal life cycle of the parasite by swallowing cystic form. Cysts in the duodenum may spread anywhere in the body hematogenously or lymphogenously via the vena porta (2,6). As natural filters, the liver and lungs are the most frequent locations for HD to develop, with 90% of cases found in these organs. The remaining 10% localize in soft tissue organs, so-called “rare locations,” such as the spleen, pancreas, gall bladder, adrenal gland, pelvis, seminal vesicle, heart, bone, breast, kidney, thyroid gland, and muscles. Many hypotheses have been put forward, but pathogenesis has not yet been revealed. We agree with the most widely accepted of them, the shunt-escape theory (2). Vertebral localization of HD is extremely rare. Only 0.5% to 2% of HD cases involve the bones, and half are in the vertebrae (3). In order of frequency, most cases are localized in thoracic, lumbar and cervical vertebrae. Bone, and particularly spinal involvement, when compared with other rare locations, is quite interesting. It is usually localized in compact bone, which contains calcium, although it is porous, in contrast with soft tissue. It was demonstrated by Dew that HD embryos localize in the corpus vertebrae due to high vascularity and invade other parts of vertebrae, surrounding tissues, and even spinal canal by forming microvesicular polycystic lesions. These grow 1 to 5 mm a year (7). In our case, consistent with the literature, there was involvement in the corpus of T4 vertebra; however, it grew only 2 mm, less than the rates found in the literature. Diagnosis may be achieved through holistic evaluation of clinical, radiological, and lab data, along with anamnesis. HD findings and symptoms depend on the involved organ, localization of the organ and the tissue, effect on neighboring tissue, rupture or complications, secondary infec-

105

tions and immunological reactions (2). Symptoms range from the most frequent, localized back pain, to complete quadriplegia (7,8). Similarly, numbness in the hands and feet, weakness, and back pain were the preliminary complaints of our patient. Radiological screening methods are the first and most important options for diagnosis. Lab tests have limited effect. As also seen in our case, appearance of HD in rare locations may lead to diagnostic difficulty, as hydatid cysts may be confused with benign or malign tumors, abscess or other cysts (2). Preoperative diagnosis in our case was neurogenic tumor destroying or extending into spinal canal. Most of the endemic regions for HD are underdeveloped or developing countries. In these regions, especially the Mediterranean basin and the Middle East, animals have always been depended upon as sources of food, transportation, labor, and security. Ideal conditions for HD are constituted when appropriate climate and ecological conditions, nomadism, low level of hygienic conditions and education, local customs and beliefs, joint feeding grounds, uncontrolled slaughtering that may take place in poor conditions and even on open ground, and presence of carnivorous animals, particularly stray or pet dogs accessing the remnants of slaughtered animals are added (6). Migration and travel from these regions spreads HD worldwide. As might be expected, the largest published case series, with 36 cases, is from our neighbor, Iraq, where HD is endemic (7). HD has serious negative effects on national revenues due to increasing health costs, as well as losses in livestock industry. In theory, HD is a controllable, even eradicable, disease. It has been controlled in small island countries like Iceland, New Zealand, Tasmania, Cyprus, and the Falkland Islands, as well as limited areas of Argentina and Chile (6). Nevertheless, factors that cause HD to spread, such as environmental conditions, hard-to-change cultural traditions and human behaviors are still in place, and it seems it will continue that way. Therefore, easiest and least expensive solution is to prevent human HD infection. Although vertebral HD is rare zoonotic infection, treatment and eradication of the cyst is challenging due to its effects on vertebral body, intervertebral disk, and epidural space. Despite surgical and medical treatment, recurrence ratio is 40% to 100%, within average of 30 months (3). Together with the challenges arising from anatomical and physiological features, treatment is very challenging. Clinicians go round in circles pursuing treatment and disease. New methods, particularly medications that can

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Respiratory Case Reports

2009. Cystic echinococcosis: chronic, complex, and still neglected. PLoS Negl Trop Dis 2011; 5:e1146. [CrossRef]

better penetrate the central nervous system, are needed to prevent recurrence, and to break the vicious cycle.

CONFLICTS OF INTEREST

2.

Calik SG, Calik M, Yesildag M, Esme H. Intramuscular hydatid cyst report of an unusual case. J Emerg Med Case Rep 2016; 7:61-3. [CrossRef]

3.

Kaloostian PE, Gokaslan ZL. Spinal hydatid disease: a multidisciplinary pathology. World Neurosurg 2015; 83:52-3. [CrossRef]

4.

Loudiye H, Aktaou S, Hassikou H, El-Bardouni A, ElManouar M, Fizazi M, et al. Hydatid disease of bone. Review of 11 cases. Joint Bone Spine 2003; 70:352-5. [CrossRef]

5.

Tappe D, Stich A, Frosch M. Emergence of polycystic neotropical echinococcosis. Emerg Infect Dis 2008; 14:292-7. [CrossRef]

6.

Moro P, Schantz PM. Echinococcosis: a review. Int J Infect Dis 2009; 13:125-33. [CrossRef]

7.

Kafaji A, Al-Zain T, Lemcke J, Al-Zain F. Spinal manifestation of hydatid disease: a case series of 36 patients. World Neurosurg 2013; 80:620-6. [CrossRef]

8.

Hall WA. Spinal parasites. World Neurosurg 2015; 83:39-40. [CrossRef]

None declared.

AUTHOR CONTRIBUTIONS Concept - M.Ç., S.G.Ç., H.E.; Planning and Design M.Ç., S.G.Ç., H.E.; Supervision - M.Ç., S.G.Ç., H.E.; Funding - M.Ç., S.G.Ç., H.E.; Materials - M.Ç., S.G.Ç., H.E.; Data Collection and/or Processing - M.Ç., S.G.Ç.; Analysis and/or Interpretation - M.Ç., S.G.Ç.; Literature Review - M.Ç., S.G.Ç.; Writing - M.Ç., S.G.Ç.; Critical Review - M.Ç., S.G.Ç.

YAZAR KATKILARI Fikir - M.Ç., S.G.Ç., H.E.; Tasarım ve Dizayn - M.Ç., S.G.Ç., H.E.; Denetleme - M.Ç., S.G.Ç., H.E.; Kaynaklar - M.Ç., S.G.Ç., H.E.; Malzemeler - M.Ç., S.G.Ç., H.E.; Veri Toplama ve/veya İşleme - M.Ç., S.G.Ç.; Analiz ve/veya Yorum - M.Ç., S.G.Ç.; Literatür Taraması - M.Ç., S.G.Ç.; Yazıyı Yazan - M.Ç., S.G.Ç.; Eleştirel İnceleme M.Ç., S.G.Ç.

REFERENCES 1.

Brunetti E, Garcia HH, Junghanss T, on behalf of the members of the International CE Workshop in Lima, Peru,

Cilt - Vol. 6 Sayı - No. 2

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Respir Case Rep 2017;6(2):107-109 DOI: 10.5505/respircase.2017.86548

OLGU SUNUMU

CASE REPORT

A Rare Case of Pleural Leiomyoma Nadir Bir Plevral Leimiyoma Olgusu

RESPIRATORY CASE REPORTS

Menduh Oruç1, Ahmet Erbey1, Didem Arslan2

Abstract

Özet

A 56-year-old female patient presented with chest pain and shortness of breath ongoing for 3 years. Chest X-ray and computed tomography of the thorax revealed mass 16 x 13 x 12 cm in size in the right middle and lower lobes. Right posterolateral thoracotomy was performed. According to frozen biopsy, mass was determined to be degenerative leiomyoma. Histopathologically, tumor consisted of packets and bundles of smooth muscle fibers without significant cellular necrosis or mitotic activity. Macroscopic appearance of the tumor was white-yellow color and texture was very hard. Due to size and location, tumor was removed with 2 incisions. Aim of this report was to emphasize the need for removal of leiomyoma due to malignant potential of pleural origin.

Elli altı yaşında kadın hasta üç yıldır devam eden göğüs ağrısı, nefes darlığı ve göğsünün sağ tarafında şişlik yakınmaları ile başvurdu. Akciğer grafisinde ve bilgisayarlı toraks tomografisinde sağ akciğerde 16x13x12 cm ebadında kitle lezyonu görüldü. Hastaya sağ torakotomi uygulandı. Kitle mediastinal plevradan kaynaklanıyordu. Tümör parçalanarak çıkarıldı. Makroskopik olarak tümör sert, düzensiz yüzeyli, beyaz-sarı renkte bir kitle idi. Histolojik olarak olarak belirgin hücresel nekroz ve mitotik aktivitesi olmayan düz kas liflerinden oluşuyordu. Amacımız çok nadir görülen plevral kaynaklı leimiyomanın malignite potansiyelinden dolayı çıkarılması gerektiğini vurgulamaktır.

Key words: Intrathoracic, benign, leiomyoma.

Pleural leiomyoma is rare, benign tumor. Leiomyoma originates from smooth muscle cells, and is usually seen in gastrointestinal and urogenital organs. It is rarely observed in the respiratory

1

Department of Thoracic Surgery, Dicle University Faculty of Medicine, Diyarbakır, Turkey 2 Department of Thoracic Surgery, Marmara University Faculty of Medicine, İstanbul, Turkey

Anahtar Sözcükler: İntratorasik, benign, leiomyom.

system; however, leiomyoma can appear in the pulmonary parenchyma, mediastinum, chest wall, diaphragm, or pleural cavity (1-5).

1

Dicle Üniversitesi Tıp Fakültesi, Göğüs Cerrahi Anabilim Dalı, Diyarbakır 2 Marmara Üniversitesi Tıp Fakültesi, Göğüs Cerrahi Anabilim Dalı, İstanbul

Submitted (Başvuru tarihi): 25.11.2016 Accepted (Kabul tarihi): 25.01.2017 Correspondence (İletişim): Menduh Oruç, Department of Thoracic Surgery, Dicle University Faculty of Medicine, Diyarbakır, Turkey e-mail: menduhor@hotmail.com

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Respiratory Case Reports

CASE A 56-year-old female patient presented at hospital with chest pain. Cytopathological diagnosis was thoracic leiomyoma based on transthoracic needle aspiration biopsy. The patient had severe chest pain with dyspnea. On physical examination, the chest wall was edematous and venous dilatations were notable, as in superior vena cava syndrome. Laboratory findings were nonspecific. Chest X-ray and computed tomography revealed thoracic leiomyoma filling about 75% of the right hemithorax (16 x 13 x 12 cm) (Figure 1 and 2). Right posterolateral thoracotomy was performed for obvious mass. Texture of the tumor was hard as a rock. Due to high vascularity and bleeding, obtaining intraoperative frozen section was very difficult. Pathological result was benign tumor. Due to large size of the tumor, second thoracotomy was performed 3 intercostal spaces below the first. Tumor was superomedially adjacent to the mediastinum and inferior to the diaphragm. Parenchyma was pushed to the hilus (Figure 3 and 4). The tumor was shredded and completely removed with 2 thoracotomies. After controlling bleeding, incisions were closed and the patient was taken to intensive care. On postoperative third day, the patient was taken to preoperative room, and after removal of chest tubes, the patient was discharged for oncological consultation.

upper respiratory tract and mediastinum. Differential diagnosis of pleural spindle cell tumor should include solitary tumor cell neoplasm, smooth muscle tumor, spindle cell carcinoma, thymoma, and sarcomatoid and lipomatous variants of mesothelioma (6-8). Usually, leiomyoma of urogenital or gastrointestinal tract is benign, smooth muscle tumor. Leiomyoma is rarely associated with respiratory tract and pleura (9-11). In the present case, degenerative leiomyoma of mature pleural origin was histopathologically diagnosed. No recurrence was observed in 1 year of follow-up. Pleural leiomyoma is typically a properly encapsulated tumor with benign histological findings; however, rarely, it can have low malignant potential (12). Few cases have been described in the literature due to uncommon occurrence. It has slow growth pattern, but can eventually become extremely large and invade the mediastinum. Asymptomatic cases may be found by chance, but with growth, tumor can cause pain, dyspnea, cough, dysphagia and superior vena cava syndrome (5,12).

Figure 2: Appearance of the mass on thorax tomography

Figure 1: Appearance of mass on chest x-ray

DISCUSSION Although the majority of pleural nodules are metastatic, benign nodules such as solitary fibrous tumor, lipoma, or hemangioma may be seen. Intrathoracic soft tissue tumors are rare, and have usually descended from the Cilt - Vol. 6 SayÄą - No. 2

Figure 3: Image of removed the mass

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A Rare Case of Pleural Leiomyoma | Oruç et al.

A.E., M.O.; Analiz ve/veya Yorum - M.O., A.E.; Literatür Taraması - A.E., M.O.; Yazıyı Yazan - M.O., A.E., D.A.; Eleştirel İnceleme - M.O., A.E.

REFERENCES 1.

White SH, Ibrahim NBN, Forrester-Wood CP, Jeyasingham K. Leiomyomas of the lower respiratory tracts. Thorax 1985; 40:306-11. [CrossRef]

2.

Hsu PK, Hsu HS, Lee HC, Hsieh CC, Wu YC, Wang LS, et al. Management of primary chest wall tumors: 14 years’ clinical experience. J Chin Med Assoc 2006; 69:377-82. [CrossRef]

3.

Qiu X, Zhu D, Wei S, Chen G, Chen J, Zhou Q. Primary Leiomyoma of the pleura. World J Surg Oncol 2011; 9:76. [CrossRef]

4.

Shaffer K, Pugatch RD, Sugarbaker DJ. Primary mediastinal leiomyoma. Ann Thorac Surg 1990; 50:301-2. [CrossRef]

5.

Rodríguez PM, Freixinet JL, Plaza ML, Camacho R. Unusual primary pleural leiomyoma. Interact Cardiovasc Thorac Surg. 2010; 10:441-2. [CrossRef]

6.

Gannon BR, O'Hara CD, Reid K, Isotalo PA. Solitary fibrous tumor of the anterior mediastinum: a rare extrapleural neoplasm. Tumori 2007; 93:508–10.

7.

Van Kolen K, Pierrache L, Heyman S, Pauwels P, Van Schil P. Prognostic factors and genetic markers in thymoma. Thoracic Cancer 2010; 1:133–40. [CrossRef]

8.

Xue X, Chen J, Ma W, Zhu D, Zhang W, Chen G, et al. Mediastinal solitary fibrous tumor with right diaphragm invasion: report of a case. SurgToday 2009; 39:332–4. [CrossRef]

9.

Proca DM, Ross P Jr, Pratt J, Frankel WL. Smooth muscle tumor of the pleura. A case report and review of the literature. Arch Pathol Lab Med 2000; 124:1688–92.

Figure 4: Thoracotomy image

In diagnosis of leiomyoma, auscultation and percussion findings can be helpful, but laboratory tests are not very valuable. Criterion standard for diagnosis is radiological imaging, in particular magnetic resonance imaging, and angiography may be added. For definitive diagnosis, however, smooth myofibers must be observed cytopathologically. Most appropriate treatment strategy is to surgically remove all of tumoral mass due to malignant transformation probability. Comparatively small tumors may be resected by video assisted surgery, but local invasion must be considered.

CONCLUSION Leiomyoma is potentially a malignant tumor, and regardless of size, must be completely removed

CONFLICTS OF INTEREST None declared.

AUTHOR CONTRIBUTIONS Concept - M.O., A.E., D.A.; Planning and Design - M.O., A.E., D.A.; Supervision - M.O., A.E., D.A.; Funding M.O., A.E.; Materials - M.O.; Data Collection and/or Processing - A.E., M.O.; Analysis and/or Interpretation M.O., A.E.; Literature Review - A.E., M.O.; Writing M.O., A.E., D.A.; Critical Review - M.O., A.E.

10. Moran CA, Suster S, Koss MN. Smooth muscle tumours presenting as pleural neoplasms. Histopathology 1995; 27:227–34. [CrossRef]

YAZAR KATKILARI

11. Nose N, Inoue M, Kodate M, Kawaguchi M, Yasumoto K. Leiomyoma originating from the extrapleural tissue of the chest wall. Jpn J Thorac Cardiovasc Surg 2006; 54:242– 5. [CrossRef]

Fikir - M.O., A.E., D.A.; Tasarım ve Dizayn - M.O., A.E., D.A.; Denetleme - M.O., A.E., D.A.; Kaynaklar - M.O., A.E.; Malzemeler - M.O.; Veri Toplama ve/veya İşleme -

12. Turhan K, Cakan A, Cagirici U. Leiomyoma: an unusual pleural tumor: report of a case. Turk Resp J 2008; 9:53– 5.

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Respir Case Rep 2017;6(2):110-113 DOI: 10.5505/respircase.2017.93585

OLGU SUNUMU

CASE REPORT

Yeni bir Tanım: Kombine Pulmoner Fibrozis ve Amfizem Sendromu A New Definition: Combined Pulmonary Fibrosis and Emphysema Syndrome

RESPIRATORY CASE REPORTS

Dildar Duman, Hakan Günen

Özet

Abstract

Kombine pulmoner fibrozis ve amfizem sendromu (KPFA), kendine özgü klinik bulguları olan ve radyolojik olarak üst lob amfizemi ve alt lob fibrozisi ile karakterize yeni tanımlanan bir sendromdur. Hastalık iyi bilinmediği için yeterince tanı konulamamaktadır. Progresif nefes darlığı şikayetiyle başvuran, 60 paket/yıl sigara öyküsü olan erkek hastanın çekilen toraks tomografisinde KPFA sendromuna özgü üst loblarda amfizem ve alt loblarda fibrozis izlendi. Hastalığın bir diğer önemli özeliği olarak FEV1 kısmen korunmuş, DLCO ise oldukça düşük bulundu. hastada pulmoner hipertansiyon saptandı. Tüm bulgularıyla KPFA sendromu tanısı konulan olgu, bu sendromuna dikkat çekmek için literatür eşliğinde sunuldu.

Combined pulmonary fibrosis and emphysema syndrome (CPFE) is a newly defined syndrome with unique clinical findings, characterized by presence of emphysema and pulmonary fibrosis seen radiologically. Since awareness of the syndrome is insufficient, CPFE is under-recognized. Male patient presented with progressive dyspnea and history of smoking 60 packs per year. Upper lobe emphysema and lower lobe fibrosis, which are specific for CPFE syndrome, were observed in chest computed tomography scans. Forced expiratory volume 1 was relatively well preserved, but diffusing capacity of the lungs for carbon monoxide was very low, and is an important feature of the disease. Pulmonary hypertension has also been determined to be characteristic finding of the syndrome. Patient was diagnosed as CPFE syndrome based on presence of all characteristic features and case is presented with review of the literature to draw attention to this disease.

Anahtar Sözcükler: Amfizem, fibrozis, pulmoner hipertansiyon.

Key words: Emphysema, fibrosis, pulmonary hypertension.

İdiyopatik pulmoner fibrozis ve amfizem farklı radyolojik, patolojik, fonksiyonel ve prognostik özelliklere sahip ayrı hastalıklardır (1). Ancak ilk olarak 2005’de amfizem ve pulmoner fibrozis birlikteliği olan ve karakteristik özellikler gösteren yeni bir antite kombine pulmoner fibrozis ve amfizem sendromu (KPFA) olarak Cottin tarafından

Süreyyapaşa Göğüs Hastalıkları ve Göğüs Cerrahisi Eğitim Araştırma Hastanesi, İstanbul

tanımlandı (2) ve son dönemde KPFA olguları yayınlanmaya başlanıldı (3). KPFA kendine özgü karakteristik özellikler taşıyan ancak farkında olunmadığı için yeterince tanı konulamayan bir sendromdur. Biz de KPFA sendromuna dikkat çekmek için bir olgumuzu sunmayı amaçladık.

Süreyyapaşa Chest Diseases and Thoracic Surgery Training and Research Hospital, İstanbul, Turkey

Başvuru tarihi (Submitted): 03.08.2016 Kabul tarihi (Accepted): 08.11.2016 İletişim (Correspondence): Dildar Duman, Süreyyapaşa Göğüs Hastalıkları ve Göğüs Cerrahisi Eğitim Araştırma Hastanesi, İstanbul e-mail: dildaryetis@yahoo.com

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Respiratory Case Reports

OLGU Elli altı yaşında erkek hasta son üç aydır artan nefes darlığı, göğüs ağrısı, baş ağrısı, yorgunluk şikayetleri ile başvurdu. Özgeçmişinde 60 paket/yıl sigara öyküsü vardı. Beş yıl önce KOAH tanısı konulmuş ve sigarayı bırakmıştı. KOAH tanısıyla IKS/LABA+LAMA kombinasyonu kullanıyordu. Fizik muayenesinde hasta pletorik görünümlüydü, +/+ pretibial ödemi mevcuttu, çomak parmağı yoktu. Solunum sistemi muayenesinde expiryumu uzun, bilateral bazallerde ralleri duyuldu. Laboratuvar tetkiklerinde patolojik olarak hemotokrit (htc) yüksekliği (htc: %59), proBNP: 555 ve D dimer: 0,7 (>0,5) bulundu. Arter kan gazı (AKG)’da hipoksi (PO2: 55, SaO2: %88) saptandı (Tablo 1). Hastanın akciğer grafisinde vasküler yapılarda genişleme, her iki akciğer üst zonda havalanma artışı ve bilateral alt zonlarda yaygın heterojen dansite artışı, retiküler izler görüldü (Şekil 1). Solunum fonksiyon testinde FEV1/FVC: %67, FEV1: 2,5 L %84, DLCO: %33 bulundu (Tablo 2). EKG’de sağ aks deviasyonu, p pulmonale ve sağ dal bloğu izlendi, EKO’da PAB 70 mmHg saptandı. Hastaya pulmoner hipertansiyon etiyolojisi araştırması ve pulmoner emboli ekartasyonu için çekilen toraks BT anjio da pulmoner trunkus dilate, sağ ve sol pulmoner arterler ektazik, pulmoner hipertansiyon ile uyumlu izlendi, pulmoner emboli saptanmadı. Parankim incelendiğinde ise bilateral üst loblarda yaygın amfizematöz görünüm, bilateral alt loblarda ise septal kalınlaşmalar, retiküler dansite artışları, bronşektazik değişiklikler ve periferik alanlarda balpeteği görünüm ve fibrozis izlendi (Şekil 2 ve 3). Kardiyoloji ile konsulte edilen ve sağ kalp kateterizasyonu yapılan hastada mPAB:45 mm Hg ve vasoreaktivite testi negatifti. Tablo 1: AKG değerleri. pH

Şekil 1: PA Akciğer grafisi. Tablo 2: SFT-DLCO değerleri. Beklenen FVC 3.82

Ölçülen 3.81

% Beklenen 100 84

FEV1

3.07

2.57

FEV1/FVC

80.2

67.4

MEF 25-75

3.53

1.44

41

PEF

8.0

7.77

97

DLCO

8.83

2.88

33

7,39

PaCO2

43 mmHg

PaO2

55 mmHg

SaO2

%88

HCO3

17mmol/L

Nefes darlığı şikâyeti ile başvuran, sigara öyküsü olan, SFT de FEV1’in kısmen korunduğu ama DLCO’nun oldukça düşük olduğu görülen ve radyolojik olarak üst loblarda amfizem ve alt loblarda fibrozisle karakterize görünümü olan ve pulmoner hipertansiyon saptanan hastada kombine pulmoner fibrozis ve amfizem (KPFA) sendromu düşünüldü. Sigarayı bırakmış olan hastanın

Cilt - Vol. 6 Sayı - No. 2

tedavisinde kullanmış olduğu bronkodilatör tedavinin yanı sıra USOT, diüretik, digoksin, flebotomi tedavileri uygulandı.

Şekil 2: Toraks BT: üst loblarda amfizem.

TARTIŞMA KPFA nadir görülen, akciğerin üst loblarında amfizem, alt loblarında fibrozis ile karakterize ancak tek başına amfizem ya da sadece fibrozis olan hastalardan farklı, kendi-

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Yeni bir Tanım: Kombine Pulmoner Fibrozis ve Amfizem Sendromu | Duman ve ark.

ne özgü klinik bulgular ve mortalite gösteren bir sendbirlikte hastalığı tanımada karakteristik klinik özellikler yol gösterici olarak kullanılır. (4). Bunlar; 1. erkek olması, 2. ağır sigara içicisi olması, 3. ciddi semptomatik olması 4. SFT’ nin kısmen korunup DLCO’nun belirgin düşmesi, 5. pulmoner hipertansiyon varlığı ve 6. akciğer kanseri insidansının daha fazla olmasıdır (4,6,7).

Şekil 3: Toraks BT: alt loblarda balpeteği ve intersiyel fibrozis.

KPFA’nın prevelansı net olarak bilinmemekle birlikte, sanılanın aksine sık rastlanılan bir sendrom olduğu ve farkındalığının artmasıyla sendromun daha fazla hastada tanımlanabileceği düşünülmektedir (8). İdiyopatik pulmoner fibrozis hastalarının tomografi kesitleri incelendiğinde %8-50’sinde amfizem varlığı tespit edilmiştir (3,9,10). Tüm IPF hastalarının %35’inde aslında KPFA olduğu düşünülmektedir ve KPFA’nın klinik seyri tek başına IPF’den farklı olduğu için bu hastalığı tanımlayabilmek önemlidir (2). Sigara kullanımı hastalığın etiyolojisinde en önemli risk faktörü olarak kabul edilmektedir, CPFE hastalarında sigara içme oranı %100’e yakındır (3). Hastalık %90 oranında erkeklerde görülmektedir, bu durum sigara içen erkeklerin amfizem gelişimine daha yatkın olmasına bağlanmıştır (3). Olgumuz da 56 yaşında, 60 paket/yıl sigara anamnezi olan erkek hasta idi. En belirgin semptom olgumuzda da olduğu gibi ileri derecede nefes darlığıdır. Fizik muayenede siyanoz, çomak parmak görülebilirken, solunum sistemi muayenesinde velcro raller oskülte edilebilmektedir (8). KPFA’lı olguların %87-100’ünde velcro raller, %43-45’inde ise çomak parmak raporlanmıştır (1,6). Hastamızın çomak parmağı yoktu ancak oskültasyonda expiryumu uzun, bilatereal bazallerde ralleri duyulmaktaydı. KPFA’da amfizeme bağlı hiperinflasyon ve fibrozise bağlı restriktif defektin dengelenmesiyle akciğer volümleri koru-

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romdur (4,5). Henüz bir konsensus tanımı olmamakla nur. Solunum fonksiyon testleri, başta FEV1 olmak üzere genellikle normaldir. Amfizem, fibrozis ve pulmoner vasküler hasarın ortak bulgusu olarak DLCO ise belirgin azalmış bulunur (5,8). Hastamızın da FEV 1’i kısmen korunmuştu (%84), DLCO ise oldukça düşük, %33 olarak saptandı. Radyolojik olarak üst loblarda amfizem, alt loblarda intestisyel fibrozis karakteristiktir (1-3). Üst loblarda paraseptal amfizem daha sıklıkla izlenmekle birlikte sentrilobüler amfizem ve büllöz değişiklikler de görülebilir (3,6). Alt loblarda da balpeteği ve retiküler dansite artışları sık görülürken, buzlu cam alanlarına da rastlanabilir (3,6). Olgumuzun da radyolojik bulguları KPFA sendromuna özgü üst loblarda amfizem ve alt loblarda interstisyel fibrozis, balpeteği ve retiküler dansite artışları ile karakterize idi. KPFA’lı hastaların arter kan gazı (AKG) analizinde hipoksi en belirgin özelliktir, istirahat esnasındaki hipoksi egzersiz ile derinleşir (1,3). KPFA’da arter kan gazı değerleri, KOAH’tan farklı, IPF’ye daha yakındır (1). Cottin ve ark. (2) çalışmalarında istirahatte PaO2: 63,1 mmHg ölçülmüş, PCO2 yüksekliği olmamıştır (2). Olgumuzun AKG’ında da PaO2: 55 mmHg, PCO2: 43 mmHg bulundu, KPFA sendromuyla uyumlu olarak hipoksi görüldü, hiperkapni saptanmadı. Pulmoner hipertansiyon (PAH) KOAH ve IPF’nin en önemli komplikasyonudur ve kötü prognozla ile ilişkilendirilir (1,11). KPFA sendromunda da PAH, KOAH ve IPF’ye göre daha sık görülür ve daha ciddi seyreder (1,3,11,12). PAH prevelansı KOAH’ta %50, , IPF’de %31-46 oranında iken, KPFA’ da PAH gelişimi %47-90 hastada bildirilmiştir (1,3,11,12). Sağ kalp kateterizasyonu ile doğrulanan PAH gelişen 40 KPFA’lı hastanın bir yıllık sağkalım oranı %60 bulunmuştur (13). Pulmoner arter sistolik basıncı 70 mm Hg bulunan hastamızda da sağ kalp kateterizasyonu ile pulmoner hipertansiyon varlığı gösterildi. CPFE hastalarının ortalama sağkalımı 2,1 ile 8,5 yıl olarak bildirilmektedir (3). Bu hastalarda akciğer kanserinin de tek başına amfizem veya IPF hastalarına göre daha çok görüldüğü, prevelansının %35,8-%46,8 arasında olduğu belirtilmiştir (1,2,4,5) KPFA’nın spesifik tedavisi yoktur (1,5). İlk yapılacak şey, sigaranın bıraktırılmasıyla hastalığın progresyonunun yavaşlatılmasıdır (1). Oksijen tedavisi hipoksemi ve pulmoner hipertansiyon için en spesifik tedavidir (1). CPFE ile takipli hastaların %80’inine 5 yıllık izlemde oksijen konsantratörü raporu yazılmıştır (5-13). Atakları ve enfeksiyonları önlemek adına aşılama önerilir (1). KPFA’lı hastawww.respircase.com


Respiratory Case Reports

ların bronkodilatörlerden fayda görüp görmediği tam bilinmemektedir, ancak genel pratikte sıkça kullanılır (1). Sigarayı bırakmış olan ve LABA+LAMA kullanan hastamıza oksijen konsantratörü raporu düzenlendi, kardiyolojinin önerisi ile diüretik ve digoksin tedavisi başlandı.

3.

Jankowich MD, Rounds SI. Combined pulmonary fibrosis and emphysema syndrome. Chest 2012; 141:222-31. [CrossRef]

4.

Ba Aqeel SH, Biswas A, Sriram PS. The worst of both worlds-combined pulmonary fibrosis and emphysema syndrome. Ann Transl Med 2016; 4:196. [CrossRef]

ÇIKAR ÇATIŞMASI

5.

Özçelik N, Özsu S. Yeni tanımlanan bir antite: kombine pulmoner fibrozis ve amfizem sendromu. Tuberk Toraks 2015; 63:48-52.

6.

Cottin V. The impact of emphysema in pulmonary fibrosis. Eur Respir Rev 2013; 22:153-7. [CrossRef]

7.

Cottin V. Clinical case: Combined pulmonary fibrosis and emphysema with pulmonary hypertension- clinical management. BMC Res Notes 2013, 6(Suppl 1):S2. [CrossRef]

8.

Ayten Ö, Okutan O. Kombine pulmoner fibrozis ve amfizem sendromu. KOAH Bülteni, Günen H, Çalıkoğlu M (Eds) 2014 (2): 8-11.

9.

Ryerson CJ, Hartman T, Elicker BM, Ley B, Lee JS, Abbritti M, et al. Clinical features and outcomes in combined pulmonary fibrosis and emphysema in idiopathic pulmonary fibrosis. Chest 2013; 144:234-40. [CrossRef]

KPFA sendromu üst lob amfizemi ve alt lob fibrozisi ile karakterize nadir bir hastalıktır. Pulmoner hipertansiyon ve mortalite ile ilişkilidir. Hastalığa tanı koyulabilmesi için öncelikle hastalığın farkında olunması gerekir. Sigara içen ve nefes darlığı olan erkeklerde radyolojik uyumluluk varsa akla gelmelidir. KPFA’nın etiyolojisi, morbidite ve mortalitesini daha iyi açıklayacak, yeni tedavi seçeneklerine imkân tanıyacak yayınlara ihtiyaç vardır.

ÇIKAR ÇATIŞMASI Bu makalede herhangi bir çıkar çatışması bildirilmemiştir.

YAZAR KATKILARI Fikir - D.D., H.G.; Tasarım ve Dizayn - D.D., H.G.; Denetleme - D.D., H.G.; Kaynaklar - D.D., H.G.; Malzemeler - D.D., H.G.; Veri Toplama ve/veya İşleme - D.D., H.G.; Analiz ve/veya Yorum - D.D., H.G.; Literatür Taraması - D.D., H.G.; Yazıyı Yazan - D.D., H.G.; Eleştirel İnceleme - H.G., D.D.

KAYNAKLAR 1.

2.

Lin H, Jiang S. Combined pulmonary fibrosis and emphysema (CPFE): an entity different from emphysema or pulmonary fibrosis alone. J Thoracic Dis 2015; 7:767-79. [CrossRef] Cottin V, Nunes H, Brillet PY, Delaval P, Devauassoux G, Tillie-Leblond I, et al. Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity. Eur respir J 2005; 26:586-93. [CrossRef]

Cilt - Vol. 6 Sayı - No. 2

10. Ye Q, Huang K, Ding Y, Lou B, Hou Z, Dai H, et al. Cigarette smoking contributes to idiopathic pulmonary fibrosis associated with emphysema. Chin Med J (Engl) 2014; 127:469-74. 11. Seeger W, Adir Y, Barbera JA, Champion H, Coghian JG, Cottin V, et al. Pulmonary hypertension in chronic lung diseases. J Am Coll Cardiol 2013; 62(25 Suppl):D10916. [CrossRef] 12. Caminati A, Cassandro R, Harari S. Pulmonary hypertension in chronic interstitial lung diseases. Eur Respir Rev 2013; 22:292-301. [CrossRef] 13. Cottin V, Le Pavec J, Prevot G, Mal H, Humbert M, Simonneau G, et al. Pulmonary hypertension in patients with combined pulmonary fibrosisand emphysema. Eur Respir J 2010; 35:105-11. [CrossRef]

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Respir Case Rep 2017;6(2):114-117 DOI: 10.5505/respircase.2017.07379

OLGU SUNUMU

CASE REPORT

Miliyer Görünüm ile Başvuran Akciğer Adenokarsinomu Adenocarcinoma Presenting with Miliary Intrapulmonary Carcinoma

RESPIRATORY CASE REPORTS

Fatih Uzer1, Hasan Şenol Coşkun2, Aykut Çilli1

Özet

Abstract

Akciğerler, küçük hücreli dışı akciğer kanserlerin sıklıkla metastaz yaptığı organlardır. Akciğer metastazları görüntüleme bulguları, pulmoner nodül, plevral effüzyon ve lenf nodu genişlemesi şeklinde olabilir. Ancak akciğer kanserlerinin miliyer dağılımı çok nadirdir. Erlotinib'e iyi yanıt veren miliyer dağılım ile seyreden bir adenokarsinom olgusu sunuldu.

The lungs are frequently metastatic organs for nonsmall cell lung cancer, and lung metastasis may present with several different patterns on chest radiography, including multiple pulmonary nodules, pleural effusion, and hilar or mediastinal adenopathy. However, lung cancer with miliary intrapulmonary carcinomatosis is an uncommon phenomenon. Presently described is a case of miliary intrapulmonary carcinoma that responded well to erlotinib treatment.

Anahtar Sözcükler: Adenokarsinom, erlotinib, miliyer dağılım.

Key words: Adenocarcinoma, erlotinib, miliary pattern.

Küçük hücreli dışı akciğer kanserlerinin en sık yayılım yeri akciğer içinedir. Akciğer metastazları görüntüleme bulguları pulmoner nodül, plevral effüzyon ve lenf nodu genişlemesi şeklinde olabilir (1). Ancak akciğer kanserlerinin miliyer dağılımı çok nadirdir. Miliyer dağılım daha çok hematojen yolla olmaktadır ve ayırıcı tanıda infeksiyon hastalıkları ile metastazik kanserler başta olmak üzere birçok hastalık düşünülmelidir (2-5). Miliyer metastazlar sıklıkla, metastatik tiroid kanseri, renal kanser ve melanomda gözlenirken, daha büyük ve

1

Akdeniz Üniversitesi Tıp Fakültesi, Göğüs Hastalıkları Anabilim Dalı, Antalya 2 Akdeniz Üniversitesi Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, Tıbbi Onkoloji Bilim Dalı, Antalya

seyrek dağılım gösteren metastazlar tipik olarak akciğer, meme ve gastrointestinal traktüsten köken alan adenokarsinomlarda görülür. Primer akciğer andeokarsinomunun miliyer metastazı ölümcül olabilir (3-6). Miliyer dağılım gösteren primer akciğer adenokarsinomları EGFR tirozin kinaz inhibitörleri ile tedavi edildiğinde daha iyi prognoz göstermektedir (8-9). Erlotinib’e iyi yanıt veren miliyer dağılım ile seyreden bir adenokarsinom olgusunu sunuyoruz.

1

Department of Respiratory Medicine, Akdeniz University Faculty of Medicine, Antalya, Turkey 2 Department of Internal Medicine Division of Medical Oncology, Akdeniz University Faculty of Medicine, Antalya, Turkey

Başvuru tarihi (Submitted): 03.11.2016 Kabul tarihi (Accepted): 12.01.2017 İletişim (Correspondence): Aykut Çilli, Akdeniz Üniversitesi Tıp Fakültesi, Göğüs Hastalıkları Anabilim Dalı, Antalya

e-mail: acilli@akdeniz.edu.tr

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OLGU Altmış iki yaşında kadın hasta bir haftadır olan öksürük şikâyeti nedeniyle hastaneye başvurdu. Fizik muayenesi olağan olan hastanın 40 paket yılı sigara öyküsü vardı. Soy geçmişinde özellik yoktu. Posterior anterior (PA) akciğer grafisinde bilateral diffüz nodüler dansite artışı vardı (Şekil 1). Bilgisayarlı toraks tomografisinde, bilateral diffüz miliyer gölgelenmeler izlendi (Şekil 2). Mevcut bulgularla hasta pnömoni olarak değerlendirilmiş olup non spesifik antibiyoterapi başlandı. Antibiyotik tedavisine cevap vermeyen hastaya bronkoskopi yapıldı. Sağ orta lobdan transbronşiyal biyopsi alındı. Biyopsinin patolojik incelenmesinde invazif adenokarsinoma tanısı konuldu. Yapılan moleküler incelemede EGFR gen mutasyonu saptandı. Hastaya Erlotinib (150 mg/gün) başlandı. Üç ay sonra klinik olarak iyileşme gösteren hastanın kontrol PA akciğer grafisi ve tomografisinde belirgin iyileşme saptandı (Şekil 3 ve 4).

Şekil 3: Tedavinin 3. ayında kontrol PA akciğer grafisi.

Şekil 4: Tedavinin 3. ayında Bilgisayarlı Tomografi görüntüleri.

TARTIŞMA

Şekil 1: Olgunun ilk başvurusundaki PA akciğer grafisi.

Şekil 2: Olgunun ilk başvurusundaki Bilgisayarlı Tomgorafi görüntüleri.

Cilt - Vol. 6 Sayı - No. 2

Multipl pulmoner nodüllerin en sık sebebi metastatik hastalıklar olmakla beraber bazı benign durumlar da multipl nodüllere neden olabilir. Ayırıcı tanıda; sarkodioz, miliyer tüberküloz, lenfoma, pulmoner histoplazmozis (özellikle bağışıklık sistemi baskılanmış hastalarda), pulmoner metastaz ile seyreden akciğer kanserleri, talk pudrası granülomatozisi, erken evre pnömokonyoz ve pulmoner hemosiderozis gibi hastalıklar düşünülmelidir (10). Akciğer kanserlerinin miliyer metastazı çok nadiren görülmektedir. Miliyer dağılım ile en sık seyreden akciğer kanseri de adenokarsinomdur. Esas olarak patolojik tanı gerekmekle beraber yüksek çözünürlüklü bilgisayarlı tomografi (YÇBT) ayırıcı tanıda yardımcı olmaktadır. Miliyer enfeksiyonlar ve hematojen yayılan metastazlar akciğer bazallerinde sekonder loblarda rastgele dağılım gösterir (5-11). Bunu YÇBT ile saptamak mümkündür. Ancak bunun hematojen yayılan bir kanser mi olduğu ya da miliyer bir enfeksiyon mu olduğu tek başına görüntüleme ile ayırt edilememektedir. Bu durumda hastanın anamnezi klinik tanıya gitmekte yar-

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Miliyer Görünüm ile Başvuran Akciğer Adenokarsinomu | Çilli ve ark.

dımcıdır. Bu tür hastalarda klinik ve immünohistokimyasal inceleme, özellikle primer odağın bilinmediği diğer malign metastazlardan ayırıcı tanıda önemlidir. Çünkü miliyer dağılım sadece bir klinik duruma spesifik olmayıp birçok hastalıkta görülebilir. Fizik muayenede cilt lezyonları, lenfadenopatiler ve plevral effüzyon saptanması nodüllerin maligniteye bağlı olabileceğini düşündürmektedir. Miliyer seyreden adenokarsinomların tanısını koymak genellikle zordur. Tanı histopatolojik olarak doğrulanmalıdır (8). Bizim olgumuzda olduğu gibi bronkoskopi yapılıp transbronşiyal biyopsi alınmalıdır. Gerekiyorsa cerrahi seçeneği de düşünülmelidir. Eskiden müsinöz bronkoalveoler karsinom (BAK) olarak tanımlanan adenokarsinomlar artık lepidik ya da invazif gelişimin yaygınlığına göre müsinöz in situ karsinom (AIS), müsinöz minimal invazif karsinom (MIA) ya da invaziv müsinöz adenokarsinom olarak sınıflanmaktadır. Lepidik büyüme paterni olan soliter adenokarsinom BT’de buzlu cam dansitesinde nodül olarak görülmektedir. Genelde kübik-nonmüsinöz ya da daha seyrek olarak kolumnar müsinöz tipte atipik epitel hücre proliferasyonlarıdır (12). Bizim olgumuz musinöz invazif adenokarsinom olarak tanı aldı. EGFR mutasyonu saptanan küçük hücreli dışı akciğer kanserlerinin EGFR tirozin kinaz inhibitörlerine iyi yanıt verdiği bilinmektedir. Toplam 3612 küçük hücreli dışı akciğer kanseri tanılı hastada yapılan bir retrospektif çalışmada, 85 hastanın miliyer dağılım gösterdiği saptanmıştır. Bu hastalardan 81’i adenokarsinom tanısı almıştır. Seksen beş hastanın 60’ında EGFR mutasyonu çalışılmış olup, 42 (%70) hastada EGFR mutasyonu saptanmıştır. Tanı anında miliyer dağılım olması kötü prognoz ile ilişkili bulunmuştur (13). Hastamızda Erlotinib (150 mg/gün) tedavisine başladık ve tedavinin üçüncü ayında belirgin klinik ve radyolojik yanıt aldık. Sonuç olarak, akciğerde miliyer pattern birçok hastalık nedeniyle olabilmektedir. Ayrıcı tanıya gitmek için YÇBT çekilmesi yardımcı olacaktır. Bu hastalarda miliyer patern ile seyredebilen akciğer adenokarsinomu da akılda tutulmalıdır.

ÇIKAR ÇATIŞMASI Bu makalede herhangi bir çıkar çatışması bildirilmemiştir.

YAZAR KATKILARI Fikir - A.Ç., F.U., H.Ş.C.; Tasarım ve Dizayn - A.Ç., F.U., H.Ş.C.; Denetleme - A.Ç., H.Ş.C., F.U.; Kaynaklar - A.Ç., H.Ş.C., F.U.; Malzemeler - .U., A.Ç.; Veri Toplama

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ve/veya İşleme - H.Ş.C., F.U., A.Ç.; Analiz ve/veya Yorum - F.U., A.Ç.; Literatür Taraması - F.U.; Yazıyı Yazan F.U., A.Ç.; Eleştirel İnceleme - A.Ç., H.Ş.C.

KAYNAKLAR 1.

Quinn D, Gianlupi A, Broste S. The changing radiographic presentation of bronchogenic carcinoma with reference to cell types. Chest 1996; 110:1474–9. [CrossRef]

2.

Kim HJ, Kang SH, Chung HW, Lee JS, Kim SJ, Yoo KH, et al. Clinical features of lung adenocarcinomas with epidermal growth factor receptor mutations and miliary disseminated carcinomatosis. Thoracic Cancer 2015; 6: 629–35. [CrossRef]

3.

Zompatori M, Bnà C, Poletti V, Spaggiari E, Ormitti F, Calabrò E, et al. Diagnostic imaging of diffuse infiltrative disease of the Lung. Respiration 2004; 71:4–19. [CrossRef]

4.

Herold CJ, Bankier AA, Fleischmann D. Lung metastases. Eur Radiol 1996; 6:596-606. [CrossRef]

5.

Voloudaki AE, Tritou IN, Magkanas EG, Chalkiadakis GE, Siafakas NM, Gourtsoyiannis N. HRCT in miliary lung disease. Acta Radiol 1999; 40: 451-6. [CrossRef]

6.

Patz EF Jr, Fidler J, Knelson M, Paine S, Goodman P. Significance of percutaneous needle biopsy in patients with multiple pulmonary nodules and a single known primary malignancy. Chest 1995; 107:601–4. [CrossRef]

7.

Sharma BB. Miliary nodules on chest radiographs: A diagnostic dilemma. Lung India 2015; 32: 518-20.

8.

Kobayashi M, Takeuchi T, Bandobashi K, Uemura Y, Ogawa Y, Ohtsuki Y, et al. Diffuse micronodular pulmonary metastasis of lung adenocarcinoma predicts gefitinib response in association with epidermal growth factor receptor mutations. Anticancer Res 2006; 26:1621-6.

9.

Laack E, Simon R, Regier M, Andritzky B, Tennstedt P, Habermann C, et al. Miliary never-smoking adenocarcinoma of the lung: strong association with epidermal growth factor receptor exon 19 deletion. J Thorac Oncol 2011; 6:199-202. [CrossRef]

10. Saleem A, Thomas EC, Wilkinson A, Azher M, Saleem N. Bilateral miliary shadowing on chest X-ray. Coll Physicians Surg Pak 2013; 23: 902-3. [CrossRef] 11. Raoof S, Amchentsev A, Vlahos I, Goud A, Naidich DP. Pictorial essay: multinodular disease. a high-resolution CT scan diagnostic algorithm. Chest 2006; 129:805–15. [CrossRef] 12. Truini A, Pereira SP, Cavazza A, Spagnolo P, Nosseir S, Longo L, et al. Classification of different patterns of pul-

www.respircase.com


Respiratory Case Reports

monary adenocarcinomas. Expert Rev Respir Med 2015; 9:571-86. [CrossRef]

cancer presenting with miliary intrapulmonary carcinomatosis. Eur Respir J 2013; 41:417–24. [CrossRef]

13. Wu SG, Hu FC, Chang YL, Lee YC, Yu CY, Chang YC, et al. Frequent EGFR mutations in nonsmall cell lung

Cilt - Vol. 6 Sayı - No. 2

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Respir Case Rep 2017;6(2):118-123 DOI: 10.5505/respircase.2017.08379

OLGU SUNUMU

CASE REPORT

Persistent Hypoxemia during Extracorporeal Membrane Oxygenation in Delayed Diagnosed Paraquat Intoxication Gecikmiş Tanılı Paraquat İntoksikasyonunda Ekstrakorporeal Membran Oksijenasyonu Sırasında Dirençli Hipoksemi

RESPIRATORY CASE REPORTS

Nermin Kelebek Girgin, Nurdan Ünlü, Işık Şenkaya Sığnak, Remzi İşçimen, Ferda Kahveci, Hadi Çağlayan

Abstract

Özet

Paraquat is a highly toxic herbicide used in agriculture worldwide that causes progressive pulmonary fibrosis (PF) due to selective accumulation in the lungs. Paraquat intoxication can result in death due to multi-organ failure within a few days or respiratory failure due to PF within a few weeks. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is currently a widely used therapeutic strategy for acute respiratory distress syndrome (ARDS). Presently described is case of a 46-year-old man who was hospitalized with ARDS and treated with V-V ECMO. Expected oxygenation levels could not be attained despite ECMO support. When excluding causes for hypoxia in this patient on ECMO, detailed medical history revealed exposure to paraquat 3 weeks previously. Severe hypoxemia persisted during V-V ECMO and the patient died on sixth day after admission. The aim of this study was to examine probable causes of persistent hypoxemia during V-V ECMO observed in this case.

Paraquat, tarımda yaygın kullanılan ve akciğerlerde birikimi sonucu ilerleyici pulmoner fibrozise neden olan toksik özelliği yüksek bir herbisiddir. Paraquat intoksikasyonunda birkaç gün içinde çoklu organ yetmezliği veya birkaç hafta içinde pulmoner fibrozise bağlı solunum yetmezliği sonucu ölüm gelişebilir. Veno-venöz ekstrakorporeal membran oksijenasyonu (V-V ECMO) günümüzde akut solunum sıkıntısı sendromunda (ARDS) yaygın olarak uygulanan bir tedavi stratejisidir. Bu yazıda ARDS tanısı ile yatırılan ve tedavi sürecinde V-V ECMO kullanılan bir olguyu sunduk. ECMO desteğine rağmen yeterli oksijenasyona ulaşılamayan ve ECMO’ya bağlı hipoksi nedenleri dışlanan olguda, tekrar sorgulanan tıbbi öyküsü sonucu üç hafta önce paraquat maruziyeti olduğu saptandı. V-V ECMO desteğine rağmen hipoksi devam eden olgu, yoğun bakıma yatışının 6. günü kaybedildi. Bu olgu aracılığı ile V-V ECMO sırasında dirençli hipoksinin nedenlerini gözden geçirmeyi amaçladık.

Key words: Paraquat intoxication, extracorporeal membrane oxygenation, hypoxemia.

Anahtar Sözcükler: Paraquat intoksikasyonu, ekstrakorporeal membran oksijenasyonu, hipoksemi.

Department of Anesthesiology and Reanimation, Uludağ University, Faculty of Medicine, Bursa, Turkey

Uludağ Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Bursa

Submitted (Başvuru tarihi): 17.11.2016 Accepted (Kabul tarihi): 07.02.2017 Correspondence (İletişim): Nermin Kelebek Girgin, Department of Anesthesiology and Reanimation, Uludağ University, Faculty of Medicine, Bursa, Turkey e-mail: nkelebek@uludag.edu.tr

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Paraquat, a compound containing 1,1′-dimethyl-4,4′bipyridinium dichloride, is an herbicide widely used in agriculture. Exposure to toxic doses can be fatal, despite aggressive medical intervention (1,2). Early toxicity includes oral, pharyngeal, esophageal, and bowel ulcerations, and necrosis, acute kidney injury, and liver failure. Late toxicity is due to retention of paraquat in alveolar macrophages, where it reacts with highly abundant oxygen to form free radicals and reactive oxygen species (2). Death may occur due to multi-organ failure or respiratory insufficiency as a result of pulmonary fibrosis (PF) (1,2). Hypoxia, which occurs secondary to many diseases, is a common sign in critically ill patients. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) in acute respiratory distress syndrome (ARDS) is currently a widely used therapeutic strategy (3,4). In this treatment, blood is drained from the superior or inferior vena cava and reinfused into the right atrium. Artificial lung membrane adequately removes blood carbon dioxide and provides oxygenation (3). It allows use of protective mechanical ventilation strategy and reduces risk of barotrauma, volutrauma, ventilator-induced lung injury, or oxygen toxicity (3,4). In some patients, however, extracorporeal support fails to restore arterial oxygenation (5). Presently described are probable causes of persistent hypoxemia during V-V ECMO in case of paraquat intoxication that was diagnosed late.

unit (ICU) with diagnosis of primary ARDS due to pneumonia. On admission to ICU, the patient's hemodynamic parameters were as follows: noninvasive blood pressure, 140/80 mm Hg; heart rate, 110 bpm; and body temperature, 36.6°C. Arterial blood gas analyses yielded following results: pH, 7.31; PaO2, 64 mm Hg on mechanical ventilation (fraction of inspired oxygen [FiO2]: 1.0); PaCO2, 53 mm Hg; HCO3, 26 mmol/L; SaO2, 90%; lactate, 14 mg/L (normal range: 4–20 mg/L). Acute Physiology and Chronic Health Evaluation II score was 22. Bilateral diffuse pulmonary infiltrates were detected on chest X-ray (Figure 1). Despite invasive mechanical ventilation with high FiO2 and positive end-expiratory pressure (PEEP) (FiO2: 1.0; PEEP: 10 cm H2O), hypoxemia and hypercarbia continued in following hours; therefore, the patient was placed in prone position. Subsequently, oxygenation improved based on arterial blood gas analysis (Table 1).

CASE A 46-year-old man weighing 70 kg who had consumed an herbicide 3 weeks prior and hidden that fact from health professionals presented at health center with sore throat. Oropharyngeal examination revealed purulent fibrin layers that bled when removed. White blood cell (WBC) count was 18,300 /µL and C-reactive protein (CRP) level was 12 mg/dL; antibiotic therapy was initiated on an outpatient basis. As the patient also developed weakness and shortness of breath, he was re-evaluated and found to have WBC count of 23,600 /µL, CRP level of 44 mg/dL and chest radiography showed bilateral infiltration. He was hospitalized in department of chest diseases with diagnosis of pneumonia and noninvasive mechanical ventilation and antibiotherapy were initiated. During treatment, urea and creatinine levels increased and hemodialysis was performed after diagnosing acute kidney injury. Renal condition subsequently improved; however, respiratory distress progressively worsened. The patient was intubated and transferred to intensive care

Cilt - Vol. 6 Sayı - No. 2

. Figure 1: Chest radiography demonstrated bilateral lung infiltrates

On fourth day after admission, V-V ECMO (Maquet, Rastatt, Germany) was emergently initiated due to severe hypoxemia. Femoro-jugular approach was attempted, but jugular cannulation could not be performed. Pneumothorax occurred inadvertently, necessitating thorax tube insertion. A femoro-femoral approach was subsequently used, in which both drainage (23 F, 38 cm) and return (21 F, 55 cm) cannula were inserted through the femoral veins (Figure 2). However, expected oxygenation levels could not be attained, despite V-V ECMO support (Table 1). Blood gas evaluation from ECMO output line revealed pH of 7.61, pO2 of 631 mm Hg, and pCO2 of 31 mm Hg; concurrent arterial blood gas sample revealed

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pH of 7.49, pO2 of 46 mm Hg, and pCO2 of 44 mm Hg. These findings indicated serious problem with oxygen metabolism. On questioning the patient's family further to elicit information on any relevant medical history, it was learned that he had attempted suicide by consuming herbicide containing paraquat (Gramoxone; Syngenta AG, Basel, Switzerland) 3 weeks earlier and had hidden this fact from the previous health center. Moreover, the patient's family did not share this information before because they did not associate his recent health condition with the earlier paraquat exposure. Quantity of paraquat consumed could not be ascertained. Pulse steroids (1 g methylprednisolone) and cyclophosphamide (15 mg/kg/d) were initiated for paraquat-induced PF that caused ARDS. Transplantation center was informed about the case. Despite ECMO support, the patient died on sixth day after admission.

Figure 2: Chest radiography image taken during extracorporeal membrane oxygenation treatment

DISCUSSION Paraquat toxicity is a major health problem in developing countries due to the lack of effective treatment, resulting in high mortality rate (overall mortality >50%) (6). Typically, severity and prognosis of acute poisoning are determined by amount of ingested toxin (1,6,7). Following ingestion, paraquat has been shown to cause significant damage to multiple organs, including the lungs, liver, kidneys, and myocardium (1,2,6). Renal failure commonly resolves within a few weeks, but lung injury is progressive, even if only a small quantity is ingested. Paraquat is actively taken up through the highly-developed polyamine uptake system, which ultimately leads to PF and respirato-

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ry failure (6,8). In this case, although we could not ascertain exact quantity of paraquat ingested, it must have been large enough to cause severe PF. After ingestion, paraquat is rapidly distributed to all organs and tissues, particularly the lungs. Paraquat concentration in the lungs is more than 10 times plasma concentration. It has been suggested that lung damage is primarily due to oxidative mechanisms (7). Paraquatinduced toxicity is a manifestation of its ability to undergo redox cycling and subsequent generation of reactive oxygen species that can cause direct cellular damage, or react further to form other reactive oxygen species and nitrite radicals. Redox cycling consumes nicotinamide adenine dinucleotide phosphate (NADPH), a key component of cell's antioxidant defense reaction. Resultant oxidative stress created by production of free radicals and depletion of NADPH directly causes cell damage (lipid peroxidation, mitochondrial toxicity, and apoptosis) (6,7). Overall, it progressively causes lung damage due to edema, hemorrhage, interstitial inflammation, and fibrosis (6,7). Hence, excessive oxygen supplementation can worsen pulmonary injury by increasing formation of oxygen free radicals (2,3,7). Since the patient had concealed history of paraquat exposure, high FiO2 levels were used for both mechanical ventilation and ECMO to treat severe hypoxemia. This may have progressively worsened existing pulmonary pathology. Although specific treatment for paraquat intoxication has not been established, early gastric lavage, administration of adsorbents, renal detoxification with hemoperfusion, immunosuppressive therapy, and lung transplantation have been attempted to reduce mortality (2,6,7). However, efficacies of these therapeutic methods remain uncertain (6). Since this patient was admitted to ICU in late phase of intoxication, only appropriate therapy possible was immunosuppression. Immunosuppression is widely used as treatment for paraquat poisoning. Theory behind treatment is that since paraquat leads to acute inflammatory response, interference may inhibit subsequent processes that lead to lung fibrosis and death (6). Most widely studied regimen uses cyclophosphamide, methylprednisolone, and dexamethasone. Zhang et al. (7) reported 3 patients who had ingested large amounts of paraquat and survived after combined therapy with hemoperfusion, cyclophosphamide, and glucocorticoid. We used cyclophosphamide and methylprednisolone, but they could only be administered late in the course of the disease in our patient.

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Table 1: Mechanical ventilation parameters and arterial blood gas analysis of the patient ICU Day 1 Day 2 Day 3 Day 3 Day 4 admission ECMO 1st hour Position Supine Supine Prone Supine Prone Supine

Day 4 ECMO 8th hour Supine

Day 5 ECMO 18th hour Supine

Day 5 ECMO 24th hour Supine

Day 5 ECMO 36th hour Supine

MV Mode

PCV

PCV

PCV

PCV

PCV

PCV

PCV

PCV

PCV

PCV

Respiratory rate

12

20

18

18

18

14

12

12

12

14

TV (mL)

400

520

580

560

560

650

660

600

580

600

8

10

12

12

15

16

16

16

16

16

FiO2

1.0

1.0

1.0

0.9

1.0

1.0

1.0

1.0

1.0

1.0

pH

7.31

7.13

7.32

7.24

7.42

7.49

7.43

7.46

7.41

7.38

PaO2 (mmHg)

64

75

56

78

51

46

59

53

45

56

PaCO2 (mmHg)

53

90

63

75

48

44

41

40

43

47

HO3 (mEq/L)

26

23

28

32

31

33

26

28

82

84

BE (mmol/L)

0.1

-1.1

4.6

5

6

10.3

2.9

4.5

3.2

2.1

SaO2 (%)

90

89

87

92

86

91

90

85

82

84

Lactate* (mg/dL)

14

6.8

11.4

13

18.9

18

23

24.9

22

20.7

107/59

115/69

169/87

135/72

160/91

180/94

174/94

161/89

92/40

154/84

121/70

116/73

84/50

110

90

90

102

134

114

114

109

100

95

104

119

119

36.5

36.4

36.4

37.3

36.7

37

36.9

37.8

36.6

36.6

36.5

36.5

36.6

PEEP (cmH2O)

BP# (mmHg)

152/99

HR# (beat/min)

116

T# (0C)

36.4

ICU: intensive care unit, ECMO: extracorporeal membrane oxygenation, MV: mechanical ventilation, PVC: pressure-controlled ventilation, TV: tidal volume, PEEP: positive end-expiratory pressure, BE: base excess. * Normal lactate levels: 4-20 mg/dL. BP: blood pressure, HR: heart rate, T: temperature. # These are minimum and maximum values at day 1, day 2 and day 3 (during supine and prone position).

Best prognostic marker for toxicity is plasma paraquat concentration. However, facilities for its measurement may not be readily available in most hospitals because of expensive equipment and associated technical problems (1,7). In our patient, we could not measure plasma levels of paraquat due to technical difficulties. Persistent hypoxemia encountered during initial period of ECMO support indicated that there could be serious problem with oxygen metabolism. Subsequently, we learned of paraquat exposure. There are other possible causes for severe hypoxemia during V-V ECMO (5). Schmidt et al. (9) described interactions between cardiac output (CO) and ECMO blood flow. They have recommended ECMO blood flow to CO ratio greater than 0.6 as an index for ECMO efficiency. Hence, it is suggested that the setting of ECMO blood flow is 60-80 mL/kg to Cilt - Vol. 6 SayÄą - No. 2

guarantee an oxygen delivery of 3 mL/kg/min (10). However, in sepsis or hyperthermia, CO is typically elevated; CO reduction can be considered to optimize ECMO blood flow to CO ratio. During veno-venous bypass, oxygenated blood is returned to venous circulation and mixed with systemic venous blood. Some of the mixed blood returns to extracorporeal circuit, and this recirculation ratio can reduce efficacy of ECMO support (recirculation ratio [%] = [oxygen saturation in drainage cannula - oxygen saturation in the superior vena cava] Ă— 100 / [oxygen saturation in return cannula - oxygen saturation in the superior vena cava]) (5). Main mechanism of hypoxemia during ARDS is intrapulmonary shunt. Therefore, modulation of pulmonary shunt may help improve oxygenation during ECMO support (pulmonary shunt [%] = [content of oxygen in pulmonary capillary blood sample -

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Persistent Hypoxemia during Extracorporeal Membrane Oxygenation in Delayed Diagnosed Paraquat Intoxication | Kelebek Girgin et al.

content of oxygen in venous blood sample] × 100 / [content of oxygen in venous blood sample - content of oxygen in arterial blood sample]) (5). Lastly, not surprisingly, oxygenator dysfunction can also cause persistent hypoxemia. In our case, ECMO blood flow fluctuated between 4500 and 5000 mL/min. Although CO level was not measured in our study, precordial echocardiography was performed and revealed normal heart function. In addition, no increase in oxygen consumption (e.g., due to sepsis or hyperthermia) was noted. ECMO output line pO2 was 631 mm Hg; hence, oxygenator dysfunction was ruled out. Even though it is possible that recirculation ratio was high because of femoro-femoral approach, it was not measured in that context at time of evaluation (pulmonary artery and superior vena cava catheters were not used). Recannulation was not considered after failed femoro-jugular attempt. Markedly severe pulmonary shunting because of progressive PF was noted. Since residual lung function was not optimal, the patient did not respond to recruitment maneuvers. However, we believe that deficient oxygen utilization due to the patient’s primary problem played significant role in failure of ECMO support. ECMO has been used successfully as a bridge to lung transplantation in paraquat intoxication (11). In our case study, ECMO was initiated as rescue therapy for ARDS, and diagnosis was established after its initiation. Despite poor outcome in our case study, ECMO support should be considered as a bridge to lung transplantation in paraquat intoxication, as previously shown (11). In addition, if ECMO is unable to provide desired oxygenation level, ECMO pump flow, oxygenator function, CO, recirculation ratio, and pulmonary shunting should be taken into consideration. In addition, etiological factors that adversely affect oxygen metabolism, such as paraquat exposure, should be considered carefully.

CONFLICTS OF INTEREST None declared.

AUTHOR CONTRIBUTIONS Concept - N.K.G., N.Ü., I.Ş.S., R.İ., F.K., H.Ç.; Planning and Design - N.K.G., N.Ü., I.Ş.S., R.İ., F.K., H.Ç.; Supervision - N.K.G., N.Ü., I.Ş.S., R.İ., F.K., H.Ç.; Funding -; Materials - H.Ç., I.Ş.S.; Data Collection and/or Processing - N.K.G., N.Ü., R.İ.; Analysis and/or Interpretation - R.İ., H.Ç., F.K.; Literature Review – N.Ü., N.K.G.; Writing - N.K.G.; Critical Review - I.Ş.Ş., F.K.

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YAZAR KATKILARI Fikir - N.K.G., N.Ü., I.Ş.S., R.İ., F.K., H.Ç.; Tasarım ve Dizayn - N.K.G., N.Ü., I.Ş.S., R.İ., F.K., H.Ç.; Denetleme - N.K.G., N.Ü., I.Ş.S., R.İ., F.K., H.Ç.; Kaynaklar -; Malzemeler - H.Ç., I.Ş.S.; Veri Toplama ve/veya İşleme N.K.G., N.Ü., R.İ.; Analiz ve/veya Yorum - R.İ., H.Ç., F.K.; Literatür Taraması - N.Ü., N.K.G.; Yazıyı Yazan N.K.G.; Eleştirel İnceleme - I.Ş.Ş., F.K.

REFERENCES 1.

Liu XW, Ma T, Qu B, Ji Y, Liu Z. Prognostic value of initial arterial lactate level and lactate metabolic clearance rate in patients with acute paraquat poisoning. Am J Emerg Med 2013; 31:1230-5. [CrossRef]

2.

Bertram A, Haenel SS, Hadem J, Hoeper MM, Gottlieb J, Warnecke G, et al. Tissue concentration of paraquat on day 32 after intoxication and failed bridge to transplantation by extracorporeal membrane oxygenation therapy. BMC Pharmacol Toxicol 2013; 6:14:45. [CrossRef]

3.

Chiumello D, Brioni M. Severe hypoxemia: which strategy to choose. Crit Care 2016; 20:132. [CrossRef]

4.

Combes A, Bréchot N, Luyt CE, Schmidt M. Extracorporeal membrane oxygenation: beyond rescue therapy for acute respiratory distress syndrome? Curr Opin Crit Care 2017; 23:60-5. [CrossRef]

5.

Nunes LB, Mendes PV, Hirota AS, Barbosa EV, Maciel AT, Schettino GP, et al; ECMO Group. Severe hypoxemia during veno-venous extracorporeal membrane oxygenation: exploring the limits of extracorporeal respiratory support. Clinics (Sao Paulo) 2014; 69:173-8. [CrossRef]

6.

Gawarammana IB, Buckley NA. Medical management of paraquat ingestion. Br J Clin Pharmacol 2011; 72:74557. [CrossRef]

7.

Zhang Q, Wu WZ, Lu YQ, Wang JZ, Shang AD, Yao F, Chen Y. Successful treatment of patients with paraquat intoxication: three case reports and review of the literature. J Zhejiang Univ Sci B 2012; 13:413-8. [CrossRef]

8.

Asl AS, Dadashzadeh P. Acute kidney injury in patients with paraquat intoxication; a case report and review of the literature. J Renal Inj Prev 2016; 5:203-6. [CrossRef]

9.

Schmidt M, Tachon G, Devilliers C, Muller G, Hekimian G, Bréchot N, et al. Blood oxygenation and decarboxylation determinants during venovenous ECMO for respiratory failure in adults. Intensive Care Med 2013; 39:83846. [CrossRef]

10. Agerstrand CL, Bacchetta MD, Brodie D. ECMO for adult respiratory failure: current use an evolving application. ASAIO J 2014; 60:255-62. [CrossRef]

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11. Walder B, Bründler MA, Spiliopoulos A, Romand JA. Successful single-lung transplantation after paraquat in-

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toxication. Transplantation 1997; 64:789-91. [CrossRef]

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Respir Case Rep 2017;6(2):124-127 DOI: 10.5505/respircase.2017.59480

OLGU SUNUMU

CASE REPORT

Nodular Splenic Sarcoidosis: A Rare Case Report Nodüler Splenik Sarkoidoz: Nadir Bir Olgu

RESPIRATORY CASE REPORTS

Mustafa Çalık1, Mihrican Yesildag2, Saniye Göknil Çalık3, Tahir Taha Bekci2, Hıdır Esme1

Abstract

Özet

Sarcoidosis is an idiopathic, multi-systemic, granulomatous disease. It most commonly involves the lungs. Herein, we present a rare and usually asymptomatic case with splenic sarcoidosis without liver involvement. A 31-year-old male patient was admitted to our clinic with cough, sputum, and shortness of breath. He reported no common systemic complaints of sarcoidosis. Thoracic and abdominal computed tomography showed multiple hypodense mediastinal lymph nodes with splenic involvement. No other intra-abdominal pathology or peripheral lymphadenopathy was detected. Mediastinoscopy was performed. Diagnosis was made histopathologically. Following the treatment, his complaints regressed. Nodular splenic involvements are uncommon. Although there have been reported thirty-nine cases of sarcoidosis with multiple nodular hepatic and splenic lesions, only three isolated splenic cases have been reported in the literature to date. Despite its rarity, extra-pulmonary sarcoidosis may cause significant morbidity and mortality. Therefore, we discuss this case to draw attention to splenic sarcoidosis without liver involvement and its manifestations, diagnosis, and clinical course.

Sarkoidoz idiyopatik multisistemik granülomatöz bir hastalıktır. En sık akciğerleri tutar. Biz nadir ve genellikle asemptomatik karaciğer tutulumu olmayan nodüler splenik sarkoidozlu bir olguyu sunduk. Otuz bir yaşındaki erkek hasta; öksürük, balgam ve nefes darlığı şikâyetleriyle kliniğimize başvurdu. Sarkoidozun yaygın sistemik bulgularından hiçbirine rastlanılmadı. Toraks ve batın BT incelenmesinde çok sayıda hipodens mediastinal lenf nodları ve dalak tutulumu vardı. Başka intra-abdominal patoloji veya periferik lenfadenopati saptanmadı. Mediastinoskopi yapıldı. Tanısı histopatolojik olarak doğrulandı. Tıbbi tedaviden sonra şikâyetleri azaldı. Nodüler splenik tutulumu nadirdir. Sarkoidozun; multiple karaciğer ve splenik tutulumu olan otuz dokuz olgu rapor edilmesine rağmen, sadece üç izole nodüler splenik tutulum literatürde bildirilmiştir. Nadirliği nedeniyle ekstrapulmoner sarkoidoz önemli morbidite ve mortaliteye neden olabilir. Bu nedenle, karaciğer tutulumu olmayan nodüler splenik sarkoidozun, belirtileri, tanısı ve klinik seyrine dikkat çekmek amacıyla bu olguyu sunduk.

Key words: Sarcoidosis, splen, intra-abdominal, splenic involvement, nodular.

1

Department of Thoracic Surgery, Health Sciences University, Konya Training and Research Hospital, Konya, Turkey 2 Department of Pulmonary Medicine, Health Sciences University, Konya Training and Research Hospital, Konya, Turkey 3 KTO Karatay University Vocational School of Health Services, Konya, Turkey

Anahtar Sözcükler: Sarkoidoz, dalak, intra-abdominal, dalak tutulumu, nodüler.

1

Sağlık Bilimleri Üniversitesi Konya Eğitim ve Araştırma Hastanesi, Göğüs Cerrahisi Kliniği, Konya 2 Sağlık Bilimleri Üniversitesi Konya Eğitim ve Araştırma Hastanesi, Göğüs Hastalıkları Kliniği, Konya 3 KTO Karatay Üniversitesi Sağlık Hizmetleri Meslek Yüksekokulu, Konya

Submitted (Başvuru tarihi): 23.12.2015 Accepted (Kabul tarihi): 09.05.2017 Correspondence (İletişim): Mustafa Çalık, Department of Thoracic Surgery, Health Sciences University, Konya Training and Research Hospital, Konya, Turkey e-mail: drmcalik@hotmail.com

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Respiratory Case Reports

Sarcoidosis is an idiopathic, multi-systemic, granulomatous disease which is often seen in young adults. It is usually characterized by hilar lymphadenopathy, pulmonary infiltration, skin, and eye lesions and also noncaseating granulomatous inflammation in the affected organs (1,2). It most commonly involves the lungs. Although each part of the body can be affected, lung (90%), peripheral lymphatic (50 to 75%), skin (60 to 80%), liver (60 to 80%), bone (1 to 35%), heart and joints (30%), eye (17%), spleen (15%), and salivary glands (5%) can be affected (3). Cough and dyspnea are the most common symptoms, and the majority of the patients are asymptomatic. Abdominal involvement is detected in 5 to 15% of the patients with imaging modalities (4,5). The most common findings on abdominal computed tomography (CT) are hepato-splenomegaly and lymphadenopathy. It rarely presents as multiple hypodense nodular lesions involving the liver and spleen (5). Herein, we present an asymptomatic and uncommon sarcoidosis case with an isolated nodular splenic involvement without liver involvement.

normal. The patient underwent bronchoscopic transbronchial biopsy which showed a benign histology. Subsequently, mediastinoscopy findings were reported as noncaseating granulomatous lymphadenitis. Due to the Stage 2 sarcoidosis and extrapulmonary organ involvement, steroid treatment was initiated. At six months, repeated CT showed regression of the lung and spleen lesions (Figure 4).

CASE A 31-year-old man was applied with cough, loss of appetite, dyspnea. On physical examination there was bilateral rhonchus’s. His medical history was non-specific. Pulmonary function tests were normal. Bilateral hilar enlargement and interstitial micronodular infiltration predominantly in the upper and middle lung zones were present on chest radiography (Figure 1). On chest CT, there were conglomerated lymphadenopathies in all mediastinal compartments and bilateral hilar regions. Ground glass opacities which were accompanied by peribronchial wall thickening and increased densities accompanied by micronodules in right major fissure were observed (Figure 2A and B). Multiple hypodense nodular lesions in splenic parenchyma were detected on abdominal CT (Figure 3). Positron emission tomography computed tomography (PET-CT) was performed due to investigate the conglomerated mediastinal lymphadenopathies and other organ involvements. It revealed extensive lymphadenopathies with increased FDG uptake in all mediastinal compartments and diffuse ground glass opacities in both lungs. Small diffuse splenic nodular lesions with an increased FDG uptake were also reported. Increased blood ACE (78 U/L) levels were seen. Blood calcium level (9.6 mg/dL) and 24-hour urine calcium level (208 mg/24h) were within normal limits. Purified Protein Derived (PPD) test (0 mm) was negative. Eye examination findings were Cilt - Vol. 6 SayĹ - No. 2

Figure 1: A Chest X-ray image showing bilateral hilar enlargement and parenchymal micronodular densities

Figure 2A and B: A CT scan of the chest showing multiple mediastinal and hilar LAPs (A). Peribronchial wall thickening, ground glass opacities and micronodules in the lungs (B)

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Nodular Splenic Sarcoidosis: A Rare Case Report | Çalık et al.

Figure 3: An abdominal CT scan showing multiple hypodense nodules in the spleen

isolated hepatic spread is in 4 and both hepatic and splenic spread simultaneously was seen in nine patients (12). Multiple hepatic and splenic involvement of sarcoidosis in 39 cases and isolated splenic involvement were reported in only three cases in English literature (5). In an extended study with 6,074 sarcoidosis patients, there were massive splenomegaly in only 20 (0.3%) of the 628 (10.3%) patients with splenomegaly (13). In our case, there was no splenomegaly, but nodular splenic involvement. The patient was asymptomatic for abdominal clinical findings. Sarcoidosis can be rarely diagnosed, when extrapulmonary organ involvement is asymptomatic. In autopsy series, it has been demonstrated that lung involvement is followed by splenic involvement. Clinical course and prognosis of sarcoidosis vary. In one third of patients with spontaneous remission, the disease becomes chronic (10 to 30%). The most commonly affected organs are the lungs, which increases morbidity and mortality (14).

CONCLUSION Figure 4: At six months of treatment, abdominal CT scan showing regression of the nodules in the spleen

DISCUSSION Sarcoidosis is a granulomatous disorder of unknown etiology which most commonly involves the lung and lymph nodes. Although it may affect several systems, the clinical course and prognosis of sarcoidosis vary. Clinical appearance and symptoms depend on the duration of the disease, affected organs, extent of involvement, and activation of granulomatous event (6). While spontaneous remission of the disease occurs in one-third of the patients, 10 to 30% of patients have chronic disease (4,7). Abdominal CT findings of sarcoidosis are LAP, splenomegaly, hepatomegaly, hypovascular nodular lesions in spleen and liver (8). Autopsy studies have shown that splenic involvement in sarcoidosis is the most common second involvement followed by lung with a ratio of 40 to 80% (9,10). Splenomegaly in physical examination is detected in 10 to 20% of the patients and it is often accompanied by hepatomegaly and rarely by hypercalcemia. In a biopsy-proven study of 49 patients, LAP in 20 of the cases, splenomegaly in 16 of them, hepatomegaly in two and hypodens nodular lesions in spleen and liver in seven of the patients were reported (11). In a review consisted of 20 patients who had splenic and hepatic hypodense lesions, isolated splenic spread is in seven patients,

126

Our case was an unusual Stage 2 sarcoidosis case with an isolated splenic involvement. Although extremely rare, it must be kept in mind by the radiologist and clinician in the differentials diagnosis of splenic nodules. Also, CT is a good option to visualize extrapulmonary organ involvement such as liver and spleen in the patients with suspected sarcoidosis.

CONFLICTS OF INTEREST None declared.

AUTHOR CONTRIBUTIONS Concept - Mu.Ç., M.Y., S.G.Ç., T.T.B., H.E.; Planning and Design - Mu.Ç., M.Y., S.G.Ç., T.T.B., H.E.; Supervision - Mu.Ç., M.Y., S.G.Ç., T.T.B., H.E.; Funding - M.Ç., S.G.Ç.; Materials - M.Ç., S.G.Ç.; Data Collection and/or Processing - M.Ç., S.G.Ç.; Analysis and/or Interpretation - M.Ç., S.G.Ç.; Literature Review - M.Ç., S.G.Ç.; Writing - M.Ç., S.G.Ç.; Critical Review - M.Ç., S.G.Ç.

YAZAR KATKILARI Fikir - M.Ç., M.Y., S.G.Ç., T.T.B., H.E.; Tasarım ve Dizayn - M.Ç., M.Y., S.G.Ç., T.T.B., H.E.; Denetleme M.Ç., M.Y., S.G.Ç., T.T.B., H.E.; Kaynaklar - M.Ç., S.G.Ç.; Malzemeler - M.Ç., S.G.Ç.; Veri Toplama ve/veya İşleme - M.Ç., S.G.Ç.; Analiz ve/veya Yorum -

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M.Ç., S.G.Ç.; Literatür Taraması - M.Ç., S.G.Ç.; Yazıyı Yazan - M.Ç., S.G.Ç.; Eleştirel İnceleme - M.Ç., S.G.Ç.

7.

Chen MY, Cai JT, Du Q, Wang LJ. Sarcoidosis of spleen presenting with solitary thrombopenia. Eur J Intern Med 2009; 20:e12. [CrossRef]

REFERENCES

8.

Yonenaga Y, Kushihata F, Inoue H, Watanabe J, Tohyama T, Sugita A, et al. Sarcoidosis manifesting as hepatic and splenic nodules mimicking ovarian cancer metastases: A case report. Oncol Lett 2015; 10:2166-70. [CrossRef]

9.

Mohan A, Sood R, Shariff N, Gulati MS, Gupta SD, Dutta AK. Sarcoidosis manifesting as massive splenomegaly: a rare occurrence. Am J Med Sci 2004; 328:170-2. [CrossRef]

1.

Baughman RP, Lower EE, du Bois RM. Sarcoidosis. Lancet 2003; 361:1111-8. [CrossRef]

2.

Gezer NS, Başara I, Altay C, Harman M, Rocher L, Karabulut N, et al. Abdominal sarcoidosis: cross-sectional imaging findings. Diagn Interv Radiol 2015; 21:111–7. [CrossRef]

3.

Thomas PD, Hunninghake GW. Current concepts of the pathogenesis of sarcoidosis. Am Rev Resp Dis 1987; 135:747-60.

4.

Warshauer D. M. Splenic sarcoidosis. Semin Ultrasound CT MRI 2007; 28:21-7. [CrossRef]

5.

Thanos L, Zormpala A, Brountzos E, Nikita A, Kelekis D. Nodular hepatic and splenic sarcoidosis in a patient with normal chest radiograph. Eur J Radiol 2002; 41:10-1. [CrossRef]

6.

Hunninghake GW, Costabel U, Ando M, Baughman R, Cordier JF, du Bois R, et al. ATS/ERS/WASOG statement on sarcoidosis. American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders. Sarcoidosis Vasc Diffuse Lung Dis 1999; 16:149-73.

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10. Kataria YP, Whitcomb ME. Splenomegaly in sarcoidosis. Arch Intern Med 1980; 140:35-7. [CrossRef] 11. Folz SJ, Johnson CD, Swensen SJ. Abdominal manifestations of sarcoidosis in CT studies. J comput AssistTomogr 1995; 19:573–9. [CrossRef] 12. Scott GC, Berman JM, Higgins JL Jr. CT patterns of nodular hepatic and splenic sarcoidosis: a review of the literature. J Comput Assist Tomogr 1997; 21:369-72. [CrossRef] 13. Sharma SK, Mohan A. Sarcoidosis: global scenario & Indian perspective. Indian J Med Res 2002; 116:221-47. 14. Baran A, Özşeker F, Güneylioğlu D, Bilgin S, Arslan S, Uyanusta Ç ve ark. Sarkoidoz: Yedi yıllık deneyim. Toraks Derg 2004; 5:160-5.

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Respir Case Rep 2017;6(2):128-131 DOI: 10.5505/respircase.2017.88942

KISA RAPOR

BRIEF COMMUNICATION

Akciğer Kanserinde Fotodinamik Tedavi Photodynamic Therapy for Lung Cancer

RESPIRATORY CASE REPORTS

Tayfun Çalışkan, Oğuzhan Okutan, Dilaver Taş, Zafer Kartaloğlu

Özet

Abstract

Fotodinamik tedavi (FTD), illüminasyon için kullanılan diyot lazer ile aktive edilen fotosensitizör ilacın hastaya verildiği bir tedavi yöntemidir. Erken evre ve endobronşiyal kritik darlığı olmayan ileri evre akciğer kanserlerinin tedavisinde kullanılmaktadır. FDT uygulaması, etkinliği, komplikasyonları ve endikasyonları kısaca anlatılmıştır.

Photodynamic therapy (PDT) is a method of treatment in which photosensitizer drug is administered to the patient and activated by diode laser used for illumination. It is used for treatment of advanced lung cancer without endobronchial critical stenosis and for early stage lung cancer. PDT application, efficacy, complications, and indications are briefly explained.

Anahtar Sözcükler: Fotodinamik tedavi, akciğer kanseri, endobronşiyal tedavi.

Fotodinamik tedavi (FDT), hedef hücreleri (kanseröz veya prekanseröz) yok etmek için ışığa duyarlı ilaç (fotosensitizör) ile kombine görülebilir dalga boyunda ışık kullanılan bir tedavi yöntemidir. Uygulaması kolay bir tedavidir ve oldukça güvenilir tümör ablasyon imkânı sağlar. Torasik maligniteler için diğer onkolojik tedaviler ile kombine kullanılabilir. Akciğer kanserinde ilk bronkoskopik FDT, Hayata ve ark. (1) tarafından 1982 yılında uygulanmıştır. Erken evre ve ileri evre, kısmen endobronşiyal obstrüksiyon yapan küçük hücreli dışı akciğer kanseri (KHDAK) tedavisinde FDT kullanımı Amerika Birleşik Devletleri’nde, 1998 yılında onaylanmıştır.

Sağlık Bilimleri Üniversitesi, Sultan Abdülhamid Han Eğitim ve Araştırma Hastanesi, Göğüs Hastalıkları Servisi, İstanbul

Key words: Photodynamic therapy, lung cancer, endobronchial treatment.

FDT uygulamasında, fotosensitizör (FS) ilaç, işlemden 48 saat önce hastaya verilir. İlaç, özel yoğunluk ve dalga boyundaki illüminasyon ile aktive olur ve ablatif fotodinamik reaksiyon gerçekleşir. İllüminasyon için diyot lazer kullanılır. Işık enerjisi ile fotosensitizör aktive olunca, tip II fotokimyasal reaksiyon meydana gelir ve hücresel sitotoksisiteyi düzenleyen reaktif tekil oksijen (1O2) oluşur. Bir ilacın, FS olması için, oksijen bağımlı tip II reaksiyona neden olması gerekir. FS, ışık salınımı ile enerji kaybeder ve buna floresans denir (2). FDT, tümörün damarsal yapılarına hasar ile ve hücrede apoptozis veya nekroz ile direkt tümör hücre ölümü sağlar (3).

Department of Pulmonology, University of Health Sciences, Sultan Abdulhamid Han Training and Research Hospital, İstanbul, Turkey

Başvuru tarihi (Submitted): 12.02.2017 Kabul tarihi (Accepted): 01.03.2017 İletişim (Correspondence): Tayfun Çalışkan, Sağlık Bilimleri Üniversitesi, Sultan Abdülhamid Han Eğitim ve Araştırma Hastanesi, Göğüs Hastalıkları Servisi, İstanbul e-mail: drtcaliskan@yahoo.com

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Respiratory Case Reports

FDT, konağın anti-tümör immün yanıtını başlatan, bir inflamatuvar reaksiyonu indükleyebilir (4). Porfirinler, en iyi bilinen fotosensitizör ilaçlardır. İlaç IV uygulanır ve illüminasyondan 48 saat önce hedef lezyonda ve/veya normal dokuda (cilt, karaciğer ve dalak) konsantre olur. Çevre dokudaki konsantrasyonu minimaldir. İnfüzyondan 5 gün sonra, tekrar infüzyon uygulamadan re-illüminasyon yapılabilir. Porfirin, değişik ışık dalga boylarında (mavi: 400 nm, yeşil: 514 nm, kırmızı: 630 nm) aktive olur. Her lezyon için illüminasyon süresi 10-20 dakikadır. En sık kullanılan iki çeşit porfirin vardır: a. Porfirin (Porfimer sodyum): Porfirin 4-8 hafta süreyle, tüm dokularda bulunur. Güneş ışığı nedeniyle, özellikle ciltte aktive olabilir ve istenmeyen fotosensitivite reaksiyonu ve cilt yanıklarına neden olabilir. Hastalar, 8 hafta sureyle gün ışığına çıkmamalı veya koruyucu şapka, gözlük ve eldiven giymelidir. Evdeki aydınlatma ışıklarının zararı yoktur. Sekiz hafta sonunda hasta, bir elinde sınırlı bir alanı güneş ışığına tutar ve bir reaksiyon olmuyorsa, diğer elde tekrarlar ve yine reaksiyon olmazsa koruma sonlandırılır. b. Mace (Taloporfin, Laserphyrin, Mono-(L)aspartilklorin e6): Porfirinin kısıtlılıklarını gidermek için üretilmiştir. Gün ışığına fotosensitivite cilt reaksiyonu 2-3 hafta süre ile görülebilir. Uygulamadan 4 saat sonra aktive olur. Daha uzun illüminasyon dalga boyuna (kırmızı ışık: 664 nm) sahiptir, bu daha kolay doku penetrasyonu sağlayabilir. Japonya'da 2002’de erken evre akciğer tümörlerinde kullanımı onaylanmıştır (5). İllüminasyon amacıyla porfirin ve Mace için onaylanmış taşınabilir sırasıyla 630 nm dalga boyunda ve 664 nm dalga boyunda diyot lazer kullanılmaktadır. Her ikisi de kırmızı ışık kullanılır ve 0,5-1 cm derinliğe penetre olabilir. Bu nedenle erken invazif veya in situ lezyonların tedavisi yapılabilir. Işık emisyon diyotları (LED), lazere göre daha ucuz olup, bu amaçla kullanılmaktadır. İllüminasyon, sadece fotosensitizörü aktive etmez, aynı zamanda, hedef lezyonun belirlenmesine yardımcı olur. Bu nedenle, doğru uygulanması, aktivasyon yanında, lezyon ablasyonu ve normal dokunun korunması acısından çok önemlidir. FOB içerisinden uygulanan, diffüzan fiberoptik prob, lezyon içerisine uygulanabilir (Şekil 1). Derinden yüzeye doğru uygulama ile normal doku hasarını azaltır (3). Uygulamada, diyot lazer FOB ile uygulanır. İllüminasyon, direkt görüntüleme ile yapılmalıdır. Lezyon boyutuna göre illüminasyon birkaç seansta uygulanabilir. Kan, kırmızı ışığı abzorbe ettiği için, başarılı bir FDT için hemostaz önemlidir. Bu işlemden 24-48 saat sonra, nekrotik ve Cilt - Vol. 6 Sayı - No. 2

potansiyel olarak tıkayıcı doku artıklarını temizlemek için takip bronkoskopisi yapılır (Şekil 2).

Şekil 1: Akciğer kanserine bağlı endobronşiyal lezyonu olan hastada diffüzan prob ile illüminasyon uygulaması. (Dr. Septimiu Murgu’nun arşivinden ve izniyle kullanılmıştır).

Şekil 2: İllüminasyondan 2 gün sonra, hedef lezyonda nekrotik debris. (Dr. Septimiu Murgu’nun arşivinden ve izniyle kullanılmıştır).

FDT, erken evre ve ileri evre akciğer kanserlerinin tedavisinde kullanılmaktadır (Tablo 1). McCaughan ve ark. (6) tarafından 18 hastaya, akciğer tümörüne bağlı obstrüksiyonu azaltmak için FDT kullanılmıştır. Hastaların %40’da bir ay sonra görülebilir tümör saptanmamış ve %57’sinde darlık %50’den fazla azalmıştır. Hastaların %60’den fazlasında, klinik iyileşme ve performans skorlarında artış saptanmıştır (6). Bir başka çalışmada, semptomatik ve endobronşiyal akciğer lezyonları olan 133 (89’u KHDAK) hastaya FDT uygulanmıştır. mMRC dispne skalasına göre, hastaların %74’de dispnede anlamlı iyileşme sağlanmıştır (7). Prospektif randomize kontrollü bir çalışmada, FDT (N=14 hasta) ve Nd: YAG lazer (N=17 hasta) karşılaştırılmıştır. FDT ile tedavi edilen hastalarda, semptomatik iyileşme daha kalıcı, daha uzun süreli (p = 0.03) ve ortalama sağ kalım daha yüksek saptanmıştır (p = 0.007) (8). FDT, eksternal radyoterapi ve brakiterapi ile kombine kullanılabilir. Büyük endobronşiyal lezyonu olan 32

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Akciğer Kanserinde Fotodinamik Tedavi | Çalışkan ve ark.

KHDAK hastası, brakiterapiden 6 hafta sonra FDT ile tedavi edilmiştir. Hastaların %81’inde lokal kontrol, %94’ünde uzak metastaz olmadan sağ kalım ve %100’ünde 24 aylık takipte sağ kalım sağlanmıştır (9). FDT ile erken evre akciğer kanseri tedavisinde, tam yanıt oranı %30-100, en azından çoğu serilerde %80 saptanmıştır (10). Ancak hastaların 1/3’ünde iki tedavi, bazılarında üç tedavi gerekmiştir. Kısmi yanıt olanlarda, uygunsa diğer tedaviler (rezeksiyon veya radyoterapi) düşünülebilir. Tablo 1: FDT Endikasyonları (10, 16). İleri Evre Akciğer Kanseri: 

Santral bronş obstrüksiyonu veya stenozu nedeniyle dispne

Obstrüktif pnömoni veya atelektazi varlığı

FDT sonrası yaygın cerrahi olasılığı

FDT sonrası rezeksiyon hacminin azalma olasılığı

Radyoterapi sonrası rekürrens

Kemoterapi ile kombine olarak hayat kalitesinin idamesi

Erken Evre Akciğer Kanseri (görüntülemede görünmeyen, endoskopik olarak görülebilen)

Furukawa ve ark. (11) 94 hastada, 114 santral erken evre akciğer kanseri lezyonuna FDT uygulamıştır. Tam yanıt oranı; lezyon <1 cm ise %93, ≥1 cm ise %58, (p<0.001), <1 cm olup başlangıçta tam yanıt olanlarda, rekürrens %12 saptanmıştır. Tümör <1 cm ise daha iyi sonuçlar elde edilmiştir. Histolojik olarak düşük-orta atipi ile olan rekürrensler, ilave FDT ile başarıyla tedavi edilmiştir. 5 yıllık sağ kalım için tümör boyutu ile değişmemiştir (%58 ve %59) (11). FDT uygulanacak hastalarda, tümörün derinliği ve kartilaj invazyonu varlığı radiyal endobronşiyal ultrasonografi (EBUS) ile değerlendirilebilir. Miyazu ve ark. (12) çalışmalarında, FDT adayı olan santral yerleşimli erken evre akciğer kanserli hastalarda, bu amaçla EBUS kullanılmış ve konvansiyonel bronkoskopi ve yüksek rezolüsyonlu bilgisayarlı tomografi ile kıyaslanmıştır. FDT uygulanacak hastalarda EBUS’un yararlı olduğu ve FDT etkinliğini arttırdığı saptanmıştır. FDT dışında erken evre akciğer kanserlerinin tedavisinde, brakiterapi, kriyoterapi ve elektrokoter kullanılmaktadır. Fraksiyonel brakiterapi, özellikle performansı ve kardiyovasküler durumu kötü, cerrahiye uygun olmayan hastalarda ve radyolojik olarak saptanan <3 cm boyutunda ve derin invazyonu olan lezyonlarda uygulanmaktadır (13).

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Pahalı bir tedavidir ve fatal hemoptizi, pnömotoraks, kardiyak aritmi ve fistül gibi komplikasyonları vardır. Kriyoterapi, özellikle <3 mm derinlikte invazyonu olan ve kıkırdak invazyonu olmayan yüzeyel lezyonlarda başarılı bir tedavi alternatifidir (13). Erken evre akciğer kanserli hastalarda %91 tam yanıt oranı sağlanmıştır (14). Tedavi alanının dar olması ve etkisinin yüzeyel olması sınırlılıklarıdır. Termokoagülasyon uygulaması, ağır displaziden invazif karsinoma kadar birçok lezyonda kullanılmıştır. Tedavi başarısı %80’dir, ancak kanama komplikasyonu vardır (13). İleri (N=636 hasta) ve erken (N=517 hasta) evre akciğer kanserli hastalarda FDT etkinliği, mortalite, morbidite, sağ kalım ve semptomatik etkinlik şeklinde değerlendirilmiştir (15). Her iki grupta da işleme ait mortalite saptanmamıştır. İleri evre hastaların %5-28’inde cilt sensitivitesi saptanmış, %18’inde fatal olmayan hemoptizi ve %2,2’sinde fatal hemoptizi ortaya çıkmıştır. Her iki grupta semptomatik etkinlik %100 ve ileri evre kanserli hastalarda, performans skalası düşük olanlarda beklendiği gibi 5 yıllık sağ kalım daha düşük saptanmıştır. Erken evre in situ tümörlerde 5 yıllık sağ kalım %90 ve tam remisyon/yanıt hastalarında %70 bulunmuştur (15). FDT komplikasyonları; güneş ışınlarına duyarlılık nedeniyle, 8 hafta içerisinde cilt yanıkları riski, kanama, bronkoplevral fistül (geç doku nekrozu nedeniyle), havayolu obstrüksiyonu (nekrotik tümör, kanama), skar gelişimi ve subepitelyal fibrozisdir. Pahalı bir tedavi yöntemidir. FDT uygulanacak ileri evre endobronşiyal lezyonu olan hastalarda, vasküler invazyon iyi değerlendirilmelidir. Hastalar, bronkoplevral fistül gelişim riski nedeniyle yakın takip edilmelidir. Sonuç olarak; FDT, kritik havayolu darlığı olmayan hastalarda, tümörün azaltılması için ve özellikle tümör çapı ≤1 cm olan ve görüntülemede ekstrabronşiyal tutulum kanıtı olmayan erken evre akciğer kanserlerinin küratif tedavisinde kullanılmaktadır (10,16). FDT, ayrıca cerrahi veya radikal radyoterapiye uygun olmayan hastalarda, lokal endobronşiyal hastalık için, rekürren akciğer kanserlerinin küratif tedavisinde düşünülmelidir (10,16).

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YAZAR KATKILARI Fikir - T.Ç., O.O., D.T., Z.K.; Tasarım ve Dizayn - T.Ç., O.O., D.T., Z.K.; Denetleme - T.Ç., O.O., D.T., Z.K.; Kaynaklar - ; Malzemeler - T.Ç., Z.K.; Veri Toplama ve/veya İşleme - O.O., D.T.; Analiz ve/veya Yorum - T.Ç., www.respircase.com


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Z.K.; Literatür Taraması - O.O., D.T.; Yazıyı Yazan - T.Ç., O.O., D.T., Z.K.; Eleştirel İnceleme - O.O., Z.K.

KAYNAKLAR 1.

Hayata Y, Kato H, Konaka C, Ono J, Matsushima Y, Yoneyama K, et al. Fiberoptic bronchoscopic laser photoradiation for tumor localization in lung cancer. Chest 1982; 82:10–4. [CrossRef]

2.

Simone CB 2nd, Friedberg JS, Glatstein E, Stevenson JP, Sterman DH, Hahn SM, et al. Photodynamic therapy for the treatment of non-small cell lung cancer. J Thorac Dis 2012; 4:63-75. [CrossRef]

9.

Freitag L, Ernst A, Thomas M, Prenzel R, Wahlers B, Macha HN. Sequential photodynamic therapy (PDT) and high dose brachytherapy for endobronchial tumour control in patients with limited bronchogenic carcinoma. Thorax 2004; 59:790–3. [CrossRef]

10. Du Rand IA, Barber PV, Goldring J, Lewis RA, Mandal S, Munavvar M, et al. British Thoracic Society guideline for advanced diagnostic and therapeutic flexible bronchoscopy in adults. Thorax 2011; 66(Suppl 3): iii1-21. [CrossRef] 11. Furukawa K, Kato H, Konaka C, Okunaka T, Usuda J, Ebihara Y. Locally recurrent central-type early stage lung cancer <1.0 cm in diameter after complete remission by photodynamic therapy. Chest 2005; 128: 3269–75. [CrossRef]

3.

Allison R, Moghissi K, Downie G, Dixon K. Photodynamic therapy (PDT) for lung cancer. Photodiagnosis Photodyn Ther 2011; 8:231-9. [CrossRef]

4.

Moffatt-Bruce S. The immunobiology of photodynamic therapy: the potential for therapeutic intervention in lung cancer. J Natl Compr Canc Netw 2012; 10(Suppl 2): S27-30. [CrossRef]

12. Miyazu Y, Miyazawa T, Kurimoto N, Iwamoto Y, Kanoh K, Kohno N. Endobronchial ultrasonography in the assessment of centrally located early-stage lung cancer before photodynamic therapy. Am J Respir Crit Care Med 2002; 165:832-7. [CrossRef]

5.

Chiaviello A, Postiglione I, Palumbo G. Targets and mechanisms of photodynamic therapy in lung cancer cells: a brief overview. Cancers (Basel) 2011; 3:1014-41. [CrossRef]

13. Guibert N, Mhanna L, Droneau S, Plat G, Didier A, Mazieres J, et al. Techniques of endoscopic airway tumor treatment. J Thorac Dis 2016; 8:3343-60. [CrossRef]

6.

McCaughan JS Jr, Williams TE Jr, Bethel BH. Photodynamic therapy of endobronchial tumors. Lasers Surg Med 1986; 6:336–45. [CrossRef]

7.

Minnich DJ, Bryant AS, Dooley A, Cerfolio RJ. Photodynamic laser therapy for lesions in the airway. Ann Thorac Surg 2010; 89:1744–8. [CrossRef]

8.

Diaz-Jiménez JP, Martínez-Ballarín JE, Llunell A, Farrero E, Rodríguez A, Castro MJ. Efficacy and safety of photodynamic therapy versus Nd-YAG laser resection in NSCLC with airway obstruction. Eur Respir J 1999; 14:800–5. [CrossRef]

Cilt - Vol. 6 Sayı - No. 2

14. Deygas N, Froudarakis M, Ozenne G, Vergnon JM. Cryotherapy in early superficial bronchogenic carcinoma. Chest 2001; 120:26-31. [CrossRef] 15. Moghissi K, Dixon K. Is bronchoscopic photodynamic therapy a therapeutic option in lung cancer? Eur Respir J 2003; 22:535–41. [CrossRef] 16. Kato H. Our experience with photodynamic diagnosis and photodynamic therapy for lung cancer. J Natl Compr Canc Netw 2012;10(Suppl 2):S3-8. [CrossRef]

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