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Yıllar içerisinde küçük hücreli dışı akciğer kanserinin mediastinal evrelemesinde, servikal mediastinoskopi endikasyonu ve sonuçlarında neler değişti?

Year 2021, Volume: 11 Issue: 1, 82 - 88, 01.04.2021

Abstract

Amaç: Bu çalışmanın amacı, yıllar içinde teknoloji ve tanı yöntemlerinde yaşanan gelişmeler sonucunda servikal mediastinoskopi (MK) endikasyon ve sonuçlarında nelerin değiştiğini gözlemlemektir.
Materyal ve Metot: Primer küçük hücreli dışı akciğer kanseri (KHDAK) tanısı alan toplam 1071 hasta retrospektif olarak değerlendirildi. MK endikasyonu, 2003-2005 yılları arasında 610 KHDAK hastasının 454'üne (Grup 1), 2017-2019 yılları arasında 461 KHDAK hastasından 261'ine (Grup 2) kondu. Çalışmadan çıkarılan hastalar sonrasında, Grup 1'de 195 hasta ve Grup 2'de 194 hasta ameliyat edildi. MK endikasyonları, MK ile klinik multiple N2, N3, tek istasyon klinik N2 tespiti, beklenmedik patolojik (p) N2 oranları ve MK'nin yanlış negatifliği açısından iki grup karşılaştırıldı.
Bulgular: Grup 1'de 610 hastanın 454'üne (% 74,4), Grup 2'deki 461 hastanın 261'ine (% 56,6) MK endikasyonu kondu (p <0.001). Grup 1'de 78 hastada (% 17,2) MK ile multipl klinik N2 ve N3 tanısı konulurken, Grup 2'de 4 hastaya (% 1,5) bu tanı kondu (p <0,001). Grup 1'de 18 hastada (% 4), Grup 2'de 27 hastada (% 10,3) klinik tek istasyon N2 tespit edildi (p = 0.001). Grup 1'de 45 hastada (% 23,1) beklenmeyen pN2 bulunurken, Grup 2'de 18 hastada (% 9,3) bulundu (p <0.001). Grup 1'de 17 hastada (% 8,7) yalancı negatiflik bulunurken, Grup 2'de ise 8 hastada (% 4,1) yanlış negatiflik bulundu (0.065). MK endikasyonları, multiple N2, N3, tek istasyon klinik N2 tanısı ve beklenmedik pN2 saptanması açısından gruplar arasında istatistiksel olarak anlamlı fark bulundu.
Sonuç: Yıllar içinde, teknolojideki ve minimal invaziv tekniklerdeki gelişmeler sonucunda, servikal mediastinoskopi endikasyonları, MK ile klinik multiple N2, N3 hastalık tespiti, cerrahide beklenmedik pN2 tespiti ve MK'nin yanlış negatiflik oranları azalmıştır.

References

  • 1. Goldstraw P, Crowley JJ, Chansky K, Dorothy JG, Patti AG, Porta RR, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumors. J Thorac Oncol 2007;2:706-714.
  • 2. R. J. Cerfolio, L. Maniscalco, and A. S. Bryant, “The treatment of patients with stage IIIA non-small cell lung cancer from N2 disease: who returns to the surgical arena and who survives,” Ann. Thorac. Surg. 2008. Vol. 86, no. 3: 912-920.
  • 3. Albain KS, Swann RS, Rusch VW, et al. Radiotherapy plus stage III chemotherapy for non-small cell lung cancer with or without surgical resection: a phase III randomized controlled trial. Lancet. 2009; 374: 379-386.
  • 4. Caitlin AS, Vivek V, Carl MP, Abigail TB, Melissa AF, Anil V, et al. Outcomes of invasive mediastinal nodal staging versus positron emission tomography staging alone for early-stage non-small cell lung cancer treated with stereotactic body radiation. Lung Cancer. 2018;117: 53-59.
  • 5. Muzaffer M, Necati C, Songül B, Abdulaziz K, Alper C, Okan S, et al. Does the efficiency of mediastinoscopy for mediastinal staging of lung cancer increase in time? Thorac Cardiovasc Surg. 2015;23:499-506.
  • 6. Zhang R, Mietchen C, Krüger M, Bettina W, Heiko G, Sabine D, et al. Endobronchial ultrasound guided fine needle aspiration versus transcervical mediastinoscopy in nodal staging of non-small cell lung cancer: a prospective comparison study. J Cardiothorac Surg 2012;7-51.
  • 7. Ettinger DS, Wood DE, Akerley W, Bazhenova LA, Borghaei H, Camidge DR, et al. NCCN guidelines insights: non-small cell lung cancer, version 4, 2016. J Natl compr cancer netw. 2016;14:255-264.
  • 8. De Leyn P, Dooms C, Kuzdzal J, Lardinois D, Passlick B, Rami-Porta R, et al. Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer. Eur J Cardiothorac Surg. 2014;45:787-798.
  • 9. Postmus PE, Kerr KM, Oudkerk M, Senan S, Waller DA, Vansteenkiste J, et al. ESMO Guidelines Committee. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:410-421.
  • 10. Silvestri GA, Gonzalez AV, Jantz MA, Margolis ML, Gould MK, Tanoue LT, et al. Methods for staging non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chester. 2013;143:50-52.
  • 11. Rusch VW, Asamura H, Watanabe H, Giroux DJ, Porta RR, Goldstraw P. “The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer, ”J. Thorac. Oncol. 2009;4:568–577.
  • 12. Lardinois D1, De Leyn P, Van Schil P, Porta RR, Waller D, Passlick B et al. .ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer.Eur J Cardiothorac Surg. 2006;30:787-792.
  • 13. Sayar A, Citak N, Metin M, Turna A, Pekçolaklar A, Kök A, et al. Comparison of video-assisted mediastinoscopy and video-assisted mediastinoscopic lymphadenectomy for lung cancer. Gen Thorac Cardiovasc Surg 2011;59:793-798.
  • 14. Carlens E, Mediastinoscopy: a method for inspection and tissue biopsy in the superior mediastinum. Dis Chest. 1959;36:343-352.
  • 15. Sarin CL, Nohl-Oser HC Mediastinoscopy: a clinical evaluation of 400 consecutive cases. Thorax. 1969;24:585-588.
  • 16. Martin LW, Correa AM, Hofstetter W, Hong WK, Komaki R, Putnam JB Jr, et al. The evolution of treatment outcomes for resected stage IIIA non-small cell lung cancer over 16 years at a single institution. J Thorac Cardiovasc Surg. 2005;130:1601-1610.
  • 17. Vyas KS, Davenport DL, Ferraris VA, Saha SP. Mediastinoscopy: Trends and Practice Patterns in the United States South Med. South Med J. 2013;10:539-544.
  • 18. Arvind K, Roman D, Umashankkar K, Rakesh K, Gopi CK, et all. Evaluation of mediastinal lymph nodes using 18F-FDG PET-CT scan and its histopathologic correlation Ann Thorac Med. 201;6:11–16.
  • 19. Hikmet B. Pozitron emissyon tomografi (pet) hıstory of positron emission tomography Bulletin of Thoracic Surgery. 2015;6:130-145.
  • 20. İlker I, Çağatay T, Salih ZK, Altan K, The role of standard and extended cervical mediastinoscopy in the staging of non-small cell lung cancer patients. Thorac Cardiovasc Surg. 2011;19:405-409.
  • 21. Lardinois D, Schallberger A, Betticher D, Ris HB. Postinduction video-mediastinoscopy is as accurate and safe as video-mediastinoscopy in patients without pretreatment for potentially operable non-small cell lung cancer, Ann Thorac Surg, 2003;75:1102-1106.
  • 22. Cho JH, Kim J, Kim K, Choi YS, Kim HK, Shim YM. A comparative analysis of video-assisted mediastinoscopy and conventional mediastinoscopy, Ann Thorac Surg, 2011;92:1007-1011.
  • 23. Yasufuku K, Pierre A, Darling G, Marc Perrot, Thomas W, Michael J, et al. A prospective controlled trial of endobronchial ultrasound-guided transbronchial needle aspiration compared with mediastinoscopy for mediastinal lymph node staging of lung cancer. J Thorac Cardiovasc Surg. 2011;142:1393-1400.
  • 24. Navani N, Fisher DJ, Tierney JF, Stephens RJ, Burdett S, NSCLC Meta-analysis Collaborative Group Lung cancer staging: accuracy is critical. The Accuracy of Clinical Staging of Stage I-IIIa Non-Small Cell Lung Cancer: An Analysis Based on Individual Participant Data. Chest. 2019;155:502-509.
  • 25. Tachi R, Hattori A, Matsunaga T, Takamochi K, Oh S, Suzuki K The impact on the prognosis of unsuspected N2 disease in non-small-cell lung cancer: indications for thorough mediastinal staging in the modern eraSurg Today. 2017;47:20-26.
  • 26. Metin M, Citak N, Sayar A, Pekcolaklar A, Melek H, Kök A, et al. The role of extended cervical mediastinoscopy in staging of non-small cell lung cancer of the left lung and a comparison with integrated positron emission tomography and computed tomography: does integrated positron emission tomography and computed tomography reduce the need for invasive procedures? J Thorac Oncol 2011;6:1713-1719.
  • 27. Lemaire A, Nikolic I, Petersen T, Haney JC, Toloza EM, Harpole DH Jr, et al. Nine-year single center experience with cervical mediastinoscopy: complications and false negative rate. Ann Thorac Surg 2006;82:1185-1189.
  • 28. Luke WP, Pearson FG, Todd TR, Patterson GA, Cooper JD. Prospective evaluation of mediastinoscopy for assessment of carcinoma of the lung. J Thorac Cardiovasc Surg 1986;91:53-56.
  • 29. Hammoud ZT, Anderson RC, Meyers BF, Guthrie TJ, Roper CL, Cooper JD, et al. The current role of mediastinoscopy in the evaluation of thoracic disease. J Thorac Cardiovasc Surg 1999;118:894-899.
  • 30. Anraku M, Miyata R, Compeau C, Shargall Y. Videoassisted mediastinoscopy compared with conventional mediastinoscopy: are we doing better? Ann Thorac Surg 2010;89:1577-41581.
  • 31. Citak N, Buyukkale S, Kok A, Celikten A, Metin M, Sayar A, et al. Does video-assisted mediastinoscopy offer lower false-negative rates for subcarinal lymph nodes compared with standard cervical mediastinoscopy? Thorac Cardiovasc Surg. 2014;62:624-630.

What has changed in the indications and outcomes of cervical mediastinoscopy for mediastinal staging in non small cell lung cancer over the years?

Year 2021, Volume: 11 Issue: 1, 82 - 88, 01.04.2021

Abstract

Objective: The aim of this study is to observe what has changed in the indications and outcomes of cervical mediastinoscopy (CM) as a result of advancements in the technology and diagnostic methods over the years.
Materials and Methods: A total of 1071 patients, diagnosed with primary non small cell lung cancer (NSCLC) were evaluated retrospectively. CM was indicated in 454 patients (Group 1) out of 610 NSCLC patients between years 2003-2005, whereas 261 patients (Group 2) out of 461 NSCLC patients between years 2017-2019. After exclusions, 195 patients in Group 1 and 194 patients in Group 2 underwent surgery. We compared two groups in terms of CM indications, detection of clinic multiple N2, N3 and single-station cN2 disease with CM, unexpected pathologic (p)N2 ratios and false negativity of CM.
Results: There were 454 of 610 patients (74.4%) in Group 1 and 261 of 461 patients (56.6%) in Group 2 were indicated with CM (p<0.001). While 78 patients (17.2%) in Group 1 were diagnosed with multiple clinics N2, N3 with CM, 4 patients (1.5%) in Group 2 (p <0.001). Single-station cN2 was detected in 18 patients (4%) in Group 1 and 27 patients (10.3%) in Group 2 (p = 0.001). While 45 patients (23.1%) had unexpected pN2 in Group 1, it was found in 18 patients (9.3%) in Group 2 (p <0.001). False negativity found in 17 patients (8.7%) in Group 1, whereas 8 patients (4.1%) in Group 2 (0.065). A statistically significant difference was found between the groups in terms of CM indications, diagnosis of clinic multiple N2, cN3, single-station cN2 and detection of unexpected pN2.
Conclusion: Over the years, as a result of advancements in technology and minimally invasive techniques, cervical mediastinoscopy indications, clinical multiple N2, cN3 disease detection with CM, unexpected pN2 detection in surgery and false negativity ratios of CM have decreased.

References

  • 1. Goldstraw P, Crowley JJ, Chansky K, Dorothy JG, Patti AG, Porta RR, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumors. J Thorac Oncol 2007;2:706-714.
  • 2. R. J. Cerfolio, L. Maniscalco, and A. S. Bryant, “The treatment of patients with stage IIIA non-small cell lung cancer from N2 disease: who returns to the surgical arena and who survives,” Ann. Thorac. Surg. 2008. Vol. 86, no. 3: 912-920.
  • 3. Albain KS, Swann RS, Rusch VW, et al. Radiotherapy plus stage III chemotherapy for non-small cell lung cancer with or without surgical resection: a phase III randomized controlled trial. Lancet. 2009; 374: 379-386.
  • 4. Caitlin AS, Vivek V, Carl MP, Abigail TB, Melissa AF, Anil V, et al. Outcomes of invasive mediastinal nodal staging versus positron emission tomography staging alone for early-stage non-small cell lung cancer treated with stereotactic body radiation. Lung Cancer. 2018;117: 53-59.
  • 5. Muzaffer M, Necati C, Songül B, Abdulaziz K, Alper C, Okan S, et al. Does the efficiency of mediastinoscopy for mediastinal staging of lung cancer increase in time? Thorac Cardiovasc Surg. 2015;23:499-506.
  • 6. Zhang R, Mietchen C, Krüger M, Bettina W, Heiko G, Sabine D, et al. Endobronchial ultrasound guided fine needle aspiration versus transcervical mediastinoscopy in nodal staging of non-small cell lung cancer: a prospective comparison study. J Cardiothorac Surg 2012;7-51.
  • 7. Ettinger DS, Wood DE, Akerley W, Bazhenova LA, Borghaei H, Camidge DR, et al. NCCN guidelines insights: non-small cell lung cancer, version 4, 2016. J Natl compr cancer netw. 2016;14:255-264.
  • 8. De Leyn P, Dooms C, Kuzdzal J, Lardinois D, Passlick B, Rami-Porta R, et al. Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer. Eur J Cardiothorac Surg. 2014;45:787-798.
  • 9. Postmus PE, Kerr KM, Oudkerk M, Senan S, Waller DA, Vansteenkiste J, et al. ESMO Guidelines Committee. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:410-421.
  • 10. Silvestri GA, Gonzalez AV, Jantz MA, Margolis ML, Gould MK, Tanoue LT, et al. Methods for staging non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chester. 2013;143:50-52.
  • 11. Rusch VW, Asamura H, Watanabe H, Giroux DJ, Porta RR, Goldstraw P. “The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer, ”J. Thorac. Oncol. 2009;4:568–577.
  • 12. Lardinois D1, De Leyn P, Van Schil P, Porta RR, Waller D, Passlick B et al. .ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer.Eur J Cardiothorac Surg. 2006;30:787-792.
  • 13. Sayar A, Citak N, Metin M, Turna A, Pekçolaklar A, Kök A, et al. Comparison of video-assisted mediastinoscopy and video-assisted mediastinoscopic lymphadenectomy for lung cancer. Gen Thorac Cardiovasc Surg 2011;59:793-798.
  • 14. Carlens E, Mediastinoscopy: a method for inspection and tissue biopsy in the superior mediastinum. Dis Chest. 1959;36:343-352.
  • 15. Sarin CL, Nohl-Oser HC Mediastinoscopy: a clinical evaluation of 400 consecutive cases. Thorax. 1969;24:585-588.
  • 16. Martin LW, Correa AM, Hofstetter W, Hong WK, Komaki R, Putnam JB Jr, et al. The evolution of treatment outcomes for resected stage IIIA non-small cell lung cancer over 16 years at a single institution. J Thorac Cardiovasc Surg. 2005;130:1601-1610.
  • 17. Vyas KS, Davenport DL, Ferraris VA, Saha SP. Mediastinoscopy: Trends and Practice Patterns in the United States South Med. South Med J. 2013;10:539-544.
  • 18. Arvind K, Roman D, Umashankkar K, Rakesh K, Gopi CK, et all. Evaluation of mediastinal lymph nodes using 18F-FDG PET-CT scan and its histopathologic correlation Ann Thorac Med. 201;6:11–16.
  • 19. Hikmet B. Pozitron emissyon tomografi (pet) hıstory of positron emission tomography Bulletin of Thoracic Surgery. 2015;6:130-145.
  • 20. İlker I, Çağatay T, Salih ZK, Altan K, The role of standard and extended cervical mediastinoscopy in the staging of non-small cell lung cancer patients. Thorac Cardiovasc Surg. 2011;19:405-409.
  • 21. Lardinois D, Schallberger A, Betticher D, Ris HB. Postinduction video-mediastinoscopy is as accurate and safe as video-mediastinoscopy in patients without pretreatment for potentially operable non-small cell lung cancer, Ann Thorac Surg, 2003;75:1102-1106.
  • 22. Cho JH, Kim J, Kim K, Choi YS, Kim HK, Shim YM. A comparative analysis of video-assisted mediastinoscopy and conventional mediastinoscopy, Ann Thorac Surg, 2011;92:1007-1011.
  • 23. Yasufuku K, Pierre A, Darling G, Marc Perrot, Thomas W, Michael J, et al. A prospective controlled trial of endobronchial ultrasound-guided transbronchial needle aspiration compared with mediastinoscopy for mediastinal lymph node staging of lung cancer. J Thorac Cardiovasc Surg. 2011;142:1393-1400.
  • 24. Navani N, Fisher DJ, Tierney JF, Stephens RJ, Burdett S, NSCLC Meta-analysis Collaborative Group Lung cancer staging: accuracy is critical. The Accuracy of Clinical Staging of Stage I-IIIa Non-Small Cell Lung Cancer: An Analysis Based on Individual Participant Data. Chest. 2019;155:502-509.
  • 25. Tachi R, Hattori A, Matsunaga T, Takamochi K, Oh S, Suzuki K The impact on the prognosis of unsuspected N2 disease in non-small-cell lung cancer: indications for thorough mediastinal staging in the modern eraSurg Today. 2017;47:20-26.
  • 26. Metin M, Citak N, Sayar A, Pekcolaklar A, Melek H, Kök A, et al. The role of extended cervical mediastinoscopy in staging of non-small cell lung cancer of the left lung and a comparison with integrated positron emission tomography and computed tomography: does integrated positron emission tomography and computed tomography reduce the need for invasive procedures? J Thorac Oncol 2011;6:1713-1719.
  • 27. Lemaire A, Nikolic I, Petersen T, Haney JC, Toloza EM, Harpole DH Jr, et al. Nine-year single center experience with cervical mediastinoscopy: complications and false negative rate. Ann Thorac Surg 2006;82:1185-1189.
  • 28. Luke WP, Pearson FG, Todd TR, Patterson GA, Cooper JD. Prospective evaluation of mediastinoscopy for assessment of carcinoma of the lung. J Thorac Cardiovasc Surg 1986;91:53-56.
  • 29. Hammoud ZT, Anderson RC, Meyers BF, Guthrie TJ, Roper CL, Cooper JD, et al. The current role of mediastinoscopy in the evaluation of thoracic disease. J Thorac Cardiovasc Surg 1999;118:894-899.
  • 30. Anraku M, Miyata R, Compeau C, Shargall Y. Videoassisted mediastinoscopy compared with conventional mediastinoscopy: are we doing better? Ann Thorac Surg 2010;89:1577-41581.
  • 31. Citak N, Buyukkale S, Kok A, Celikten A, Metin M, Sayar A, et al. Does video-assisted mediastinoscopy offer lower false-negative rates for subcarinal lymph nodes compared with standard cervical mediastinoscopy? Thorac Cardiovasc Surg. 2014;62:624-630.
There are 31 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Article
Authors

Volkan Erdoğu This is me

Yunus Aksoy This is me

Atilla Pekçolaklar This is me

Muzaffer Metin This is me

Publication Date April 1, 2021
Published in Issue Year 2021 Volume: 11 Issue: 1

Cite

APA Erdoğu, V., Aksoy, Y., Pekçolaklar, A., Metin, M. (2021). Yıllar içerisinde küçük hücreli dışı akciğer kanserinin mediastinal evrelemesinde, servikal mediastinoskopi endikasyonu ve sonuçlarında neler değişti?. Kafkas Journal of Medical Sciences, 11(1), 82-88.
AMA Erdoğu V, Aksoy Y, Pekçolaklar A, Metin M. Yıllar içerisinde küçük hücreli dışı akciğer kanserinin mediastinal evrelemesinde, servikal mediastinoskopi endikasyonu ve sonuçlarında neler değişti?. KAFKAS TIP BİL DERG. April 2021;11(1):82-88.
Chicago Erdoğu, Volkan, Yunus Aksoy, Atilla Pekçolaklar, and Muzaffer Metin. “Yıllar içerisinde küçük hücreli dışı akciğer Kanserinin Mediastinal Evrelemesinde, Servikal Mediastinoskopi Endikasyonu Ve sonuçlarında Neler değişti?”. Kafkas Journal of Medical Sciences 11, no. 1 (April 2021): 82-88.
EndNote Erdoğu V, Aksoy Y, Pekçolaklar A, Metin M (April 1, 2021) Yıllar içerisinde küçük hücreli dışı akciğer kanserinin mediastinal evrelemesinde, servikal mediastinoskopi endikasyonu ve sonuçlarında neler değişti?. Kafkas Journal of Medical Sciences 11 1 82–88.
IEEE V. Erdoğu, Y. Aksoy, A. Pekçolaklar, and M. Metin, “Yıllar içerisinde küçük hücreli dışı akciğer kanserinin mediastinal evrelemesinde, servikal mediastinoskopi endikasyonu ve sonuçlarında neler değişti?”, KAFKAS TIP BİL DERG, vol. 11, no. 1, pp. 82–88, 2021.
ISNAD Erdoğu, Volkan et al. “Yıllar içerisinde küçük hücreli dışı akciğer Kanserinin Mediastinal Evrelemesinde, Servikal Mediastinoskopi Endikasyonu Ve sonuçlarında Neler değişti?”. Kafkas Journal of Medical Sciences 11/1 (April 2021), 82-88.
JAMA Erdoğu V, Aksoy Y, Pekçolaklar A, Metin M. Yıllar içerisinde küçük hücreli dışı akciğer kanserinin mediastinal evrelemesinde, servikal mediastinoskopi endikasyonu ve sonuçlarında neler değişti?. KAFKAS TIP BİL DERG. 2021;11:82–88.
MLA Erdoğu, Volkan et al. “Yıllar içerisinde küçük hücreli dışı akciğer Kanserinin Mediastinal Evrelemesinde, Servikal Mediastinoskopi Endikasyonu Ve sonuçlarında Neler değişti?”. Kafkas Journal of Medical Sciences, vol. 11, no. 1, 2021, pp. 82-88.
Vancouver Erdoğu V, Aksoy Y, Pekçolaklar A, Metin M. Yıllar içerisinde küçük hücreli dışı akciğer kanserinin mediastinal evrelemesinde, servikal mediastinoskopi endikasyonu ve sonuçlarında neler değişti?. KAFKAS TIP BİL DERG. 2021;11(1):82-8.