Klinik Araştırma
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Güneydoğu Anadolu Bölgesindeki Non-Hodgkin Lenfoma Sınıflaması: 550 Hastanın İncelenmesi

Yıl 2019, Cilt: 16 Sayı: 3, 556 - 561, 25.12.2019
https://doi.org/10.35440/hutfd.627797

Öz



Amaç: Hodgkin olmayan lenfoma
(NHL) alt tiplerinin dağılması tüm dünyada farklılık gösterir. Bu çalışmada,
Ocak 2005- Aralık 2014 tarihleri arasında hastanemize başvuran NHL hastalarında
cinsiyet, yaş, alt tipler, biyopsi alanları, nodal ve ekstranodal yerleşim
alanı ve hastalığın evrelerini değerlendirmeyi amaçladık.



Materyal ve Metod: Ocak 2005- Aralık 2014
tarihleri arasında hastanemize başvuran NHL hastalarının dosyaları retrospektif
olarak tarandı.



Bulgular: 550 hastanın 335'i (%60,9)
erkek, 215'i (%39,1) kadındı. Tüm hastaların üzerinde yaş ortalaması 56 idi
(15-95). Kadınların yaş ortalaması 57 (15-88), erkeklerin yaş ortalaması 54
(15-95) idi. NHL hastalarının histolojik alt tipleri şu şekildedir: 447 hasta (%81,3)
B hücreli lenfoma, 84 hasta (%15,2) T / NK hücre lenfoması, 19 hasta (% 3.5)
sınıflandırılmamış alt tip. NHL hastaları 2001 ve 2008 WHO (Dünya Sağlık
Örgütü) Sınıflandırmasına ve histopatolojik alt tiplerine göre alt tiplere
ayrıldı: Diffüz Büyük B Hücreli Lenfoma (DLBCL) 295 hasta (% 53,63), küçük
lenfositik lenfoma (SLL) 37 hasta ( % 6.7), Ekstranodal marjinal bölge
lenfoması (MALT tipi) 37 hasta (% 6,75), periferik T hücreli Lenfoma 27 hasta
(% 4,9), manto hücreli lenfoma 26 hasta (% 4,72), Nodal Marjinal Bölge B-Hücre
Lenfoması 7 hasta (% 1,3), 12 hastada foliküler lenfoma (% 2,1), Burkitt
lenfoma 7 hasta (% 1,3), Splenik marjinal bölge B hücreli lenfoma 4 hasta
(0,7). NHL'nin en sık görülen alt tipi DLBCL 295 hastasıydı (%53,63). Foliküler
lenfomalar merkezimizde daha az görülür. Ekstranodal invlolvement oranı
hastaların%38,5'i idi. Ekstranodal NHL'lerin bölgelerinin dağılımına göre,
hastaların%43'ünde GI kanal tutulumu vardı. En sık etkilenen GI bölgeleri mide
idi (%27,8). Bu çalışmada, hastaların %22,9'u Evre 1, Evre 2'de%26,7, Evre 3'te%19,5,
Ann-Arbor sınıflandırmasına göre Evre 4'te%30,9 idi.



Sonuç: NHL hastalarının
özellikleri coğrafi farklılıklara göre değişmektedir. Bu çalışma geriatrik
değerlendirmenin önemini ortaya koydu. NHL erkeklerde daha sık gözlendi.
Çevresel risk faktörleri epidemiyolojik olarak araştırılmalıdır. NHL'nin en
yaygın alt tipi DLBL'dir. Foliküler lenfomalar merkezimizde daha az görülür.
Ulusal kanser kayıt sisteminin iyileştirilmesi ve NHL'nin erken tanı ve
tedavisini sağlamak için tedavi protokollerini gözden geçiren çok merkezli
büyük ölçekli çalışmalara ihtiyaç vardır.




Kaynakça

  • References1- Jaffe ES, Harris. N.L., Stein H, Vardiman JW. WHO classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues Lyon: IARC; 2001..
  • 2-Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5-29.
  • 3-Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al (Eds). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer: Lyon, France, 2008.
  • 4-Anderson JR, Armitage JO, Weisenburger DD. Epidemiology of the non-Hodgkin’s lymphomas: distributions of the major subtypes differ by geographic locations. Non-Hodgkin’s Lymphoma Classification Project Ann Oncol 1998; 9(7): 717–720.
  • 5-Laurini J, Perry A, Boilesen E, Diebold J, MacLennan K, Muller- Hermelink H, et al. Classification of non-Hodgkin lymphoma in Central and South America: a review of 1028 cases. Blood 2012; 120(24): 4795–4801.
  • 6-Devesa SS, Silverman DT, Young JL Jr, Pollack ES, Brown CC, Horm JW, et al. Cancer incidence and mortality trends among whites in the United States, 1947–84. J Natl Cancer Inst 1987;79:701–70.
  • 7-Howe HL, Wingo PA, Thun MJ, Ries LA, Rosenberg HM, Feigal EG, et al. Annual report to the nation on the status of cancer (1973 through 1998), featuring cancers with recent increasing trends. J Natl Cancer Inst 2001;93:824–42.
  • 8-Hartge P, Devesa SS. Quantification of the impact of known risk factors on time trends in non-Hodgkin's lymphoma incidence. Cancer Res 1992;52(19 Suppl):5566s–9s
  • 9- Shiels MS, Engels EA, Linet MS, Clarke CA, Li J, Hall HI, Hartge P, Morton LMCancer Epidemiol Biomarkers Prev June 2013 22; 1069. The Epidemic of Non–Hodgkin Lymphoma in the United States: Disentangling the Effect of HIV, 1992–2009
  • 10- Jaffe ES, Harris. N.L., Stein H, Vardiman JW. WHO classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues Lyon: IARC; 2001.
  • 11- Smith A, Crouch S, Howell D, Burton C, Patmore R, Roman E.Cancer Epidemiol. 2015 Sep 2. pii: S1877-7821(15)00179-4. doi: 10.1016/j.canep.2015.08.015
  • 12- Haddadin WJ . Malignant lymphoma in Jordan:a retrospective analysis of 347 cases according to the World Health Organization classification. Ann Saudi Med 2005; 25: 398– 403.
  • 13- Abdel-Fattah MM , Yassine OG . Non-Hodgkin ’ s lymphomas in Alexandria, Egypt; incidence rates and trend study (1995 – 2004) . Eur J Cancer Prev 2007 ; 16 : 479 – 485 .
  • 14- Boudjerra N1, Perry AM, Audouin J, Diebold J, Nathwani BN, MacLennan KA, Müller-Hermelink HK, Bast M, Boilesen E, Armitage JO, Weisenburger DD.Classification of non-Hodgkin lymphoma in Algeria according to the World Health Organization classification.Leuk Lymphoma. 2015 Apr;56(4):965-70. doi: 10.3109/10428194.2014.939967. Epub 2014 Aug 20
  • 15- Fetica B, Achimas-Cadariu P, Pop B, Dima D, Petrov L, Perry AM et al.. Non-Hodgkin lymphoma in Romania: a single-centre experience. Hematol Oncol. 2015 Oct 20. doi:10.1002/hon.2266. [Epub ahead of print]
  • 16- Isikdogan A, Ayyildiz O, Buyukcelik A, Arslan A, Tiftik N, Buyukbayram H, et al. Non-Hodgkin’s lymphoma in southeast Turkey: clinicopathologic features of 490 cases. Ann Hematol 2004; 83(5): 265–9.
  • 17-McDuffie HH1, Pahwa P, McLaughlin JR, Spinelli JJ, Fincham S, Dosman JA, Robson D, Skinnider LF, Choi NW. Non-Hodgkin's lymphoma and specific pesticide exposures in men: cross-Canada study of pesticides and health Cancer Epidemiol Biomarkers Prev. 2001 Nov;10(11):1155-63
  • 18- Neasham D1, Sifi A, Nielsen KR, Overvad K, Raaschou-Nielsen O, Tjønneland A, Barricarte A et al. Occupation and risk of lymphoma: a multicentre prospective cohort study (EPIC). Occup Environ Med. 2011 Jan;68(1):77-81. doi: 10.1136/oem.2009.048173. Epub 2010 Sep 30.
  • 19- Ramis R, Diggle P, Boldo E, Garcia-Perez J, Fernandez-Navarro P, Lopez-Abente G. Analysis of matched geographical areas to study potential links between environmental exposure to oil refineries and non-Hodgkin lymphoma mortality in Spain. Int J Health Geogr. 2012 Feb 6;11:4.
  • 20- Dotlic S, Perry AM, Petrusevska G, Fetica B, Diebold J, MacLennan KA et al. Classification of non-Hodgkin lymphoma in South-eastern Europe: review of 632 cases from the international non-Hodgkin lymphoma classification project. Br J Haematol. 2015 Nov;171(3):366-72.
  • 21- Zucca E, Cavalli F (2000) Extranodal lymphomas. Ann Oncol 11 [Suppl 3]:219–222
  • 22- Di Leonardo G, Ginaldi L, De Martinis M, Stati M, Quaglino D (2000) Extranodal localizations of lymphoma. Clinico-epidemiologic study of 353 cases (abstract) (in Italian). Recenti Prog Med 91:500–506
  • 23- Grogan TM, Jaramillo MA, Miller TP (2001) Natural history, diagnosis, and staging of the non-Hodgkin’s lymphomas. In:Haskell CM (ed) Cancer treatment. Philadelphia, WB Saunders, pp 1338–1375
  • 24- Zucca E, Roggero E, Bertoni F, Cavalli F (1997) Primary extranodal non-Hodgkin’s lymphomas. Part 1: gastrointestinal, cutaneous and genitourinary lymphomas. Ann Oncol 8:727–737
  • 25 -A. Ünal, B. Eser, M. Çetin, M. Altınbaş, E. Karahacıoğlu, O. Kontaş, B. Kaplan, Ö. Er ve H. Ş.Coşkun, “Clinico-pathologic characteristics of non-Hodgkin’s lymphoma patients at single center in Central Anatolia,” 25th European Society for Medical Oncology Congress, 13-17 October 2000, Hamburg Germany. Annals of Oncology, 11(Suppl 4), 102, 2000.
  • 26- Arican A, Dincol D, Akbulut H, Onur H, Demirkazik A, Cay F, et al. (1999) Clinicopathologic features and prognostic factors of primary extranodal non-Hodgkin’s lymphomas in Turkey. Am J Clin Oncol 22:587–592
  • 27- Paydas S, Kekec Y, Zorludemir S (1996) Gastro-intestinal lymphoma in southern Turkey. Cent Afr J Med 42:56–60
  • 28- Yaqo RT , Hughson MD , Sulayvani FK , et al . Malignant lymphoma in northern Iraq: a retrospective analysis of 270 cases according to the World Health Organization classification. Indian J Cancer 2011 ; 48 : 446 – 451 .
  • 29- Mozaheb Z , Aledavood A , Farzad F . Distributions of major subtypes of lymphoid malignancies among adults in Mashhad, Iran . Cancer Epidemiol 2011 ; 35 : 26 – 29 .
  • 30- Liu J, Song B, Fan T, Huang C, Xie C, Li J, Zhong W, Li S, Yu J. Pathological and clinical characteristics of 1,248 non-Hodgkin's lymphomas from a regional cancer hospital in Shandong, China. Asian Pac J Cancer Prev. 2011;12(11):3055-61.
  • 31- Akhtar S S, Haque I U, Wafa S M, e t a l. Malignant lymphoma in Al-Qassim, Saudi Arabia, reclassified according to the WHO classification. Saudi Med J 2009; 30: 677– 681.
  • 32- Castella A , Joshi S , Raaschou T , et al . Pattern of malignant lymphoma in the United Arab Emirates–a histopathologic and immunologic study in 208 native patients . Acta Oncol 2001; 40: 660– 664.
  • 33- Ameen R, Sajnani KP, Albassami A, et al . Frequencies of non-Hodgkin ’s lymphoma subtypes in Kuwait: comparisons between different ethnic groups. Ann Hematol 2010; 89: 179– 184.

Classification of Non-Hodgkin Lymphoma in Southeast Turkey: A Review of 550 Cases

Yıl 2019, Cilt: 16 Sayı: 3, 556 - 561, 25.12.2019
https://doi.org/10.35440/hutfd.627797

Öz

Background: The
distribution of non-Hodgkin lymphoma (NHL) subtypes differs around the world.
In this study we aimed to evaluate the gender, age, subtypes, biopsy sites,
nodal and extranodal residential area, and stage of disease in the patients
with NHL admitted to our hospital between January 2005 and December 2014.

Materials and Methods: The records of
NHL patients admitted to our hospital between January 2005 and December 2014
were retrospectively reviewed

Results: Among 550
patients, 335 patients (60.9%) were male, 215 patients (39.1%) were female. The
average age of over all the patients was 56 years (15-95). The average age of
women was 57 (15-88), the average age of men was 54 years (15-95). The
histological subtypes of NHL patients were as follows: 447 patients (81.3%)
B-cell lymphoma, 84 patients (15.2%) T / NK cell lymphoma, 19 patients (3.5%)
unclassified subtype. NHL patients divided into subtypes according  to 2001 and 
2008 WHO (World Health Organization) Classification and histopathologic
subtypes were as follow: Diffuse Large B Cell Lymphoma (DLBCL) 295 patients
(53,63%), small lymphocytic lymphoma (SLL) 37 patients (6.7%), Extranodal
marginal zone lymphoma (MALT type) 37 patients (6,75%), peripheral T-cell
Lymphoma 27 patients (4.9%), mantle cell lymphoma 26 patients (4.72%), Nodal
Marginal Zone B-Cell Lymphoma 7 patients (1,3%), follicular lymphoma in 12
patients (2.1%), Burkitt's lymphoma 7 patients (1.3%), Splenic marginal zone
B-cell lymphoma 4 patients (0,7). The most common subtype of NHL was DLBCL 295
patients (53,63%). Follicular lymphomas are less common in our center.
Extranodal involvement rate was 38,5% of patients. According to the
distribution of the sites of extranodal NHLs, the vast majority of patients 43%
had GI tract involvement. The most commonly affected GI sites were stomach (27,8%).
In this study 22.9% of the patients were in Stage 1, 26.7% in Stage 2, 19.5% in
Stage 3, 30.9% in Stage 4 according to Ann- Arbor classification. In
conclusion, the characteristics of NHLs in our region show
some differences from other sites of the world.







Conclusions: The
characteristics of NHL patients vary according to geographical
differences.  Present study has revealed
the importance of geriatric assessment. NHL was observed frequently in men.
Environmental risk factors have to research, epidemiologically.  The most common subtype of NHL was DLBL.
Follicular lymphomas are less common in our center. Improvement of national
cancer registration system and multicenter large-scale studies reviewing the
treatment protocols are needed to ensure the early diagnosis and therapy of
NHL.

Kaynakça

  • References1- Jaffe ES, Harris. N.L., Stein H, Vardiman JW. WHO classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues Lyon: IARC; 2001..
  • 2-Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5-29.
  • 3-Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al (Eds). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer: Lyon, France, 2008.
  • 4-Anderson JR, Armitage JO, Weisenburger DD. Epidemiology of the non-Hodgkin’s lymphomas: distributions of the major subtypes differ by geographic locations. Non-Hodgkin’s Lymphoma Classification Project Ann Oncol 1998; 9(7): 717–720.
  • 5-Laurini J, Perry A, Boilesen E, Diebold J, MacLennan K, Muller- Hermelink H, et al. Classification of non-Hodgkin lymphoma in Central and South America: a review of 1028 cases. Blood 2012; 120(24): 4795–4801.
  • 6-Devesa SS, Silverman DT, Young JL Jr, Pollack ES, Brown CC, Horm JW, et al. Cancer incidence and mortality trends among whites in the United States, 1947–84. J Natl Cancer Inst 1987;79:701–70.
  • 7-Howe HL, Wingo PA, Thun MJ, Ries LA, Rosenberg HM, Feigal EG, et al. Annual report to the nation on the status of cancer (1973 through 1998), featuring cancers with recent increasing trends. J Natl Cancer Inst 2001;93:824–42.
  • 8-Hartge P, Devesa SS. Quantification of the impact of known risk factors on time trends in non-Hodgkin's lymphoma incidence. Cancer Res 1992;52(19 Suppl):5566s–9s
  • 9- Shiels MS, Engels EA, Linet MS, Clarke CA, Li J, Hall HI, Hartge P, Morton LMCancer Epidemiol Biomarkers Prev June 2013 22; 1069. The Epidemic of Non–Hodgkin Lymphoma in the United States: Disentangling the Effect of HIV, 1992–2009
  • 10- Jaffe ES, Harris. N.L., Stein H, Vardiman JW. WHO classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues Lyon: IARC; 2001.
  • 11- Smith A, Crouch S, Howell D, Burton C, Patmore R, Roman E.Cancer Epidemiol. 2015 Sep 2. pii: S1877-7821(15)00179-4. doi: 10.1016/j.canep.2015.08.015
  • 12- Haddadin WJ . Malignant lymphoma in Jordan:a retrospective analysis of 347 cases according to the World Health Organization classification. Ann Saudi Med 2005; 25: 398– 403.
  • 13- Abdel-Fattah MM , Yassine OG . Non-Hodgkin ’ s lymphomas in Alexandria, Egypt; incidence rates and trend study (1995 – 2004) . Eur J Cancer Prev 2007 ; 16 : 479 – 485 .
  • 14- Boudjerra N1, Perry AM, Audouin J, Diebold J, Nathwani BN, MacLennan KA, Müller-Hermelink HK, Bast M, Boilesen E, Armitage JO, Weisenburger DD.Classification of non-Hodgkin lymphoma in Algeria according to the World Health Organization classification.Leuk Lymphoma. 2015 Apr;56(4):965-70. doi: 10.3109/10428194.2014.939967. Epub 2014 Aug 20
  • 15- Fetica B, Achimas-Cadariu P, Pop B, Dima D, Petrov L, Perry AM et al.. Non-Hodgkin lymphoma in Romania: a single-centre experience. Hematol Oncol. 2015 Oct 20. doi:10.1002/hon.2266. [Epub ahead of print]
  • 16- Isikdogan A, Ayyildiz O, Buyukcelik A, Arslan A, Tiftik N, Buyukbayram H, et al. Non-Hodgkin’s lymphoma in southeast Turkey: clinicopathologic features of 490 cases. Ann Hematol 2004; 83(5): 265–9.
  • 17-McDuffie HH1, Pahwa P, McLaughlin JR, Spinelli JJ, Fincham S, Dosman JA, Robson D, Skinnider LF, Choi NW. Non-Hodgkin's lymphoma and specific pesticide exposures in men: cross-Canada study of pesticides and health Cancer Epidemiol Biomarkers Prev. 2001 Nov;10(11):1155-63
  • 18- Neasham D1, Sifi A, Nielsen KR, Overvad K, Raaschou-Nielsen O, Tjønneland A, Barricarte A et al. Occupation and risk of lymphoma: a multicentre prospective cohort study (EPIC). Occup Environ Med. 2011 Jan;68(1):77-81. doi: 10.1136/oem.2009.048173. Epub 2010 Sep 30.
  • 19- Ramis R, Diggle P, Boldo E, Garcia-Perez J, Fernandez-Navarro P, Lopez-Abente G. Analysis of matched geographical areas to study potential links between environmental exposure to oil refineries and non-Hodgkin lymphoma mortality in Spain. Int J Health Geogr. 2012 Feb 6;11:4.
  • 20- Dotlic S, Perry AM, Petrusevska G, Fetica B, Diebold J, MacLennan KA et al. Classification of non-Hodgkin lymphoma in South-eastern Europe: review of 632 cases from the international non-Hodgkin lymphoma classification project. Br J Haematol. 2015 Nov;171(3):366-72.
  • 21- Zucca E, Cavalli F (2000) Extranodal lymphomas. Ann Oncol 11 [Suppl 3]:219–222
  • 22- Di Leonardo G, Ginaldi L, De Martinis M, Stati M, Quaglino D (2000) Extranodal localizations of lymphoma. Clinico-epidemiologic study of 353 cases (abstract) (in Italian). Recenti Prog Med 91:500–506
  • 23- Grogan TM, Jaramillo MA, Miller TP (2001) Natural history, diagnosis, and staging of the non-Hodgkin’s lymphomas. In:Haskell CM (ed) Cancer treatment. Philadelphia, WB Saunders, pp 1338–1375
  • 24- Zucca E, Roggero E, Bertoni F, Cavalli F (1997) Primary extranodal non-Hodgkin’s lymphomas. Part 1: gastrointestinal, cutaneous and genitourinary lymphomas. Ann Oncol 8:727–737
  • 25 -A. Ünal, B. Eser, M. Çetin, M. Altınbaş, E. Karahacıoğlu, O. Kontaş, B. Kaplan, Ö. Er ve H. Ş.Coşkun, “Clinico-pathologic characteristics of non-Hodgkin’s lymphoma patients at single center in Central Anatolia,” 25th European Society for Medical Oncology Congress, 13-17 October 2000, Hamburg Germany. Annals of Oncology, 11(Suppl 4), 102, 2000.
  • 26- Arican A, Dincol D, Akbulut H, Onur H, Demirkazik A, Cay F, et al. (1999) Clinicopathologic features and prognostic factors of primary extranodal non-Hodgkin’s lymphomas in Turkey. Am J Clin Oncol 22:587–592
  • 27- Paydas S, Kekec Y, Zorludemir S (1996) Gastro-intestinal lymphoma in southern Turkey. Cent Afr J Med 42:56–60
  • 28- Yaqo RT , Hughson MD , Sulayvani FK , et al . Malignant lymphoma in northern Iraq: a retrospective analysis of 270 cases according to the World Health Organization classification. Indian J Cancer 2011 ; 48 : 446 – 451 .
  • 29- Mozaheb Z , Aledavood A , Farzad F . Distributions of major subtypes of lymphoid malignancies among adults in Mashhad, Iran . Cancer Epidemiol 2011 ; 35 : 26 – 29 .
  • 30- Liu J, Song B, Fan T, Huang C, Xie C, Li J, Zhong W, Li S, Yu J. Pathological and clinical characteristics of 1,248 non-Hodgkin's lymphomas from a regional cancer hospital in Shandong, China. Asian Pac J Cancer Prev. 2011;12(11):3055-61.
  • 31- Akhtar S S, Haque I U, Wafa S M, e t a l. Malignant lymphoma in Al-Qassim, Saudi Arabia, reclassified according to the WHO classification. Saudi Med J 2009; 30: 677– 681.
  • 32- Castella A , Joshi S , Raaschou T , et al . Pattern of malignant lymphoma in the United Arab Emirates–a histopathologic and immunologic study in 208 native patients . Acta Oncol 2001; 40: 660– 664.
  • 33- Ameen R, Sajnani KP, Albassami A, et al . Frequencies of non-Hodgkin ’s lymphoma subtypes in Kuwait: comparisons between different ethnic groups. Ann Hematol 2010; 89: 179– 184.
Toplam 33 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Klinik Tıp Bilimleri
Bölüm Araştırma Makalesi
Yazarlar

Mehmet Önder Ekmen 0000-0002-2034-6469

Sinan Dal 0000-0002-5994-2735

Abdullah Karakuş Bu kişi benim

Hüseyin Büyükbayram Bu kişi benim 0000-0002-7168-1507

Mehmet Orhan Ayyıldız Bu kişi benim 0000-0001-5673-8408

Yayımlanma Tarihi 25 Aralık 2019
Gönderilme Tarihi 1 Ekim 2019
Kabul Tarihi 19 Aralık 2019
Yayımlandığı Sayı Yıl 2019 Cilt: 16 Sayı: 3

Kaynak Göster

Vancouver Ekmen MÖ, Dal S, Karakuş A, Büyükbayram H, Ayyıldız MO. Classification of Non-Hodgkin Lymphoma in Southeast Turkey: A Review of 550 Cases. Harran Üniversitesi Tıp Fakültesi Dergisi. 2019;16(3):556-61.

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty