Mustafa BALCI, H. Belma KOÇER, Buket ALTUN ÖZDEMİR

MİDE KANSERLİ HASTALARDA PREOPERATİF SERUM CRP VE IL-6’NIN PROGNOSTİK DEĞERİ

AMAÇ: İnterlökin-6 (IL-6) inflamasyon ve tümör oluşumunda anjiogenesiz yolaklarında rol oynar. C-reaktif protein (CRP) inflamasyon belirtecidir ve birçok kanserin progresyonuna eşlik etmektedir. Bu çalışmada, mide kanseri tanısı ile ameliyat edilen hastalarda preoperatif CRP ve IL-6 düzeylerinin prognoza etkisi araştırıldı. GEREÇ VE YÖNTEM: Kliniğimizde mide kanseri tanısıyla elektif koşullarda ameliyat edilen 45 hasta çalışmaya dahil edildi. Hastaların demografik, histopatolojik ve klinik özellikleri değerlendirildi. Preoperatif dönemde alınan kan örneklerinde CRP ve IL-6 düzeyleri çalışıldı. BULGULAR: IL-6 düzeyinin tanıdaki metastaz, mortalite ve CRP düzeyi ile anlamlı ilişkisi saptandı. CRP düzeyine etki eden faktörler ise, uzak metastaz, mortalite, CEA ve IL-6 olarak belirlendi. Multivaryant analizde CRP yüksekliğinin IL-6 düzeyini başka faktörlerden bağımsız olarak artırdığı saptandı. Hastalıksız sağkalımı etkileyen faktörler; CA 19-9, IL-6, CRP yüksekliği, kötü differensiyasyon, ileri tümör evresi, Lauren sınıflandırması, preoperatif metastaz varlığı olarak saptandı. IL-6, CRP, CEA yüksekliği, differensiyasyon, evre, duvar invazyon kalınlığı, Lauren sınıflamasında diffüz tip bulunması, lenfatik invazyon varlığı, preoperatif metastaz varlığı ve hastanın kemoterapi tedavisi alması toplam sağkalıma etki eden faktörler olarak saptandı. Nüks ve/veya metastaz gelişme riski; tanıda CRP değeri yüksek olan hastalarda 6.8 kat, hastalığa bağlı mortalite riski IL-6 değeri yüksek olan hastalarda 15.9 kat fazladır. SONUÇ: Mide kanserinde, preoperatif serum CRP ve IL-6 düzeylerinin ölçülmesi, hastalığın malignite potansiyelini ve progresyonunu yansıtır. Bu nedenle hastaların takibi ve tedaviye yanıtlarını monitörize etmede yararlı tümör belirteçleri olarak kullanılabilirler.

PROGNOSTIC VALUE OF PREOPERATIVE CRP AND IL-6 LEVELS IN GASTRIC CARCINOMA PATIENTS

AIM: Interleukin-6 (IL-6) plays a role in pathways in inflammation and angiogenesis in tumor formation. C-reactive protein (CRP) is a marker of inflamation and accompanies the progression of many cancers.In this study, the effect of preoperative CRP and IL-6 levels on the prognosis of patients with gastric cancer was investigated. MATERIALS AND METHODS: Forty-five patients who underwent elective surgery for gastric cancer in our clinic between January 2002 and April 2004 were included in the study. Demographic, histopathological and clinical characteristics of the patients were evaluated. CRP and IL-6 levels were measured in preoperative blood samples. RESULTS: IL-6 levels were significantly correlated with preoperative metastasis, mortality, and CRP levels. Factors affecting CRP levels were preoperative and postoperative metastasis, mortality, CEA, and IL-6. Multivariate analysis showed that CRP elevation increased IL-6 levels independently of other factors. Factors affecting diseasefree survival were; CA 19-9, IL-6, CRP, differentiation, tumor stage, Lauren classification, and presence of preoperative metastasis. Factors affecting total survival were; IL-6, CRP, CEA elevation, differentiation, stage, wall invasion thickness, presence of diffuse type in Lauren classification, presence of lymphatic invasion, presence of preoperative metastasis, and chemotherapy treatment. CONCLUSION: Measurement of preoperative serum CRP and IL-6 levels in gastric cancer reflects the malignant potential and progression of the disease. Therefore, they can be used as useful tumor markers in monitoring patients and monitoring their response to treatment.

PDF

___

1.)Roder JD, Böttcher K, Siewert JR, et al. Prognostic factors in gastric carcinoma. Results of the German Gastric Carcinoma Study 1992. Cancer. 1993; 72: 2089-97.
2.)Korenaga D, Haraguchi M, Okamura T, et al. DNA ploidy and tumor invasion in human gastric cancer. Histopathologic differentiation. Arch Surg. 1989; 124: 314-8.
3.)Ming SC. Gastric carcinoma. A pathological classification. Cancer. 1977; 39: 2475-85.
4.)Cimerman M, Repse S, Jelenc F, et al. Comparison of Lauren’s, Ming’s and WHO histological classifications of gastric cancer as a prognostic factor for operated patients. Int Surg. 1994; 79: 27-32.
5.)Moore JR. Gastric carcinoma: 30-year review. Can J Surg. 1986; 29: 25-8.
6.)Layke JC, Lopez PP. Gastric cancer: diagnosis and treatment options. Am Fam Physicians. 2004; 69: 1133-40.
7.)Yokota T, Kunii Y, Saito T, et al. Prognostic factors for gastric cancer in the elderly. Eur J Surg Oncol. 2001; 27: 451-3.
8.)Guggenheim D.E, Shah MA. Gastric cancer epidemiology and risk factors. J Surg Oncol. 2013; 107: 230-6.
9.)den Hoed CM, Kuipers EJ. Gastric Cancer: How Can We Reduce the Incidence of this Disease?. Curr Gastroenterol Rep. 2016; 18: 34.
10.)Korenaga D, Moriguchi S, Orita H, et al. Trends in survival rates in Japanese patients with advenced carcinoma of stomach. Surg Gynecol Obstet.1992; 174: 387-93.
11.)Lawrence W Jr, Menck HR, Steele GD Jr, et al. The National Cancer Data Base Report on gastric cancer. Cancer. 1995; 75: 1734-44.
12.)Böttcher K, Becker K, Busch R, et al. Prognostic factors in stomach cancer. Results of a uni- and multivariate analysis. Chirurg. 1992; 63: 656-61.
13.)Msika S, Chastang C, Houry S, et al. Lymph node involvement as the only prognostic factor in curative resected gastric carcinoma: a multivariate analysis. World J Surg. 1989; 13: 118-23.
14.)Okusa T, Nakane Y, Boku T, et al. Quantitative analysis of nodal involvement with respect to survival rate after curative gastrectomy for carcinoma. Surg Gynecol Obstet. 1990; 170: 488-94.
15.)Siewert JR, Böttcher K, Roder JD, et al. Prognostic relevance of systematic lymph node dissection in gastric carcinoma. German Gastric Carcinoma Study Group. Br J Surg. 1993; 80: 1015-8.
16.)Gall FP, Hermanek P. Systematic lymph node dissection in curative therapy of stomach cancer. Chirurg. 1993; 64: 1024-31.
17.)Compan AF, Medrano J, Calpena R, et al. Gastric carcinoma: study of the most eminent prognostic factors. Eur J Surg Oncol. 1993; 19: 533-8.
18.)Steälä LP, Kosma VM, Marin S, et al. Prognostic factors in gastric cancer: the value of vasculer invasion, mitotic rate and lymphoplasmacytic infiltration. Br J Cancer. 1996; 74: 766-72.
19.)Gabbert HE, Meier S, Gerharz CD, et al. Tumor-cell dissociation at the invasive front: a new prognostic parameter in gastric cancer patients. Int J Cancer. 1992; 50: 202-7.
20.)Nakane Y, Okamura S, Akehira K, et al. Correlation of preoperative carcinoembryonic antigen levels and prognosis of gastric cancer patients. Cancer. 1994; 73: 2703-8.
21.)Heiss MM, Babic R, Allgayer H, et al. Tumor -associated proteolysis and prognosis: new functional risk factors in gastric cancer defined by the urokinase-type plasminogen activator system. J Clin Oncol. 1995; 13: 2084-93.
22.)Lisborg P, Jatzko G, Horn M, et al. Radical surgery (R2 resection) for gastric cancer. A multivariate analysis. Scand J Gastroenterol. 1994; 29: 1024-8.
23.)Kubota T. New chemotherapy strategies for gastric cancer. In Vivo. 2008; 22: 273-8.
24.)Sasako M, Sakuramoto S, Katai H, et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011; 29: 4387-93.
25.)Plukker JT, Mulder NH, Sleijfer DT, et al. Chemotherapy and surgery for locally advanced cancer of the cardia and fundus: phase II to study with methotrexate and 5-fluouracil. Br J Surg. 1991; 78: 955-8.
26.)De Vita F, Romano C, Orditura M, et al. Interleukin-6 serum correlates with survival in advanced gastrointestinal cancer patients but is not an independent ptognostic indicator. J Interferon Cytokine Res. 2001; 21: 45-52.
27.)Komoda H, Tanaka Y, Honda M, et al. Interleukin-6 levels in colorectal cancer tissues. World J Surg. 1998; 22: 895-8.
28.)Łukaszewicz-Zajac M, Mroczko B, Szmitkowski M. Rola interleukiny 6 oraz białka C-reaktywnego w raku zoładka [The role of interleukin-6 and C-reactive protein in gastric cancer]. Pol Merkur Lekarski. 2010; 29: 382-6.
29.)Kim DK, Oh SY, Kwon HC, et al. Clinical significances of preoperative serum interleukin-6 and C-reactive protein level in operable gastric cancer. BMC Cancer. 2009; 9: 155.
30.)Guo J, Chen S, Chen Y, et al. Combination of CRP and NLR: a better predictor of postoperative survival in patients with gastric cancer. Cancer Manag Res. 2018; 10: 315-21.
31.)Nozoe T, Iguchi T, Adachi E, et al. Preoperative elevation of serum C-reactive protein as an independent prognostic indicator for gastric cancer. Surg Today. 2011; 41: 510-3.
32.)Shrotriya S, Walsh D, Bennani-Baiti N, et al. C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review. PLoS One. 2015; 10: e0143080.
33.)Jiang X, Hiki N, Nunobe S, et al. Prognostic importance of the inflammation-based Glasgow prognostic score in patients with gastric cancer. Br J Cancer. 2012 Jul 10; 107: 275-9.
34.)Ashizawa T, Okada R, Suzuki Y, et al. Clinical significance of interleukin-6 (IL-6) in the spread of gastric cancer: role of IL-6 as a prognostic factor. Gastric Cancer. 2005; 8: 124-31.
35.)Wu CW, Wang SR, Chao MF, et al. Serum interleukin-6 levels reflect disease status of gastric cancer. Am J Gastroenterol. 1996; 91: 1417-22.
36.)Kim HK, Song KS, Park YS, et al. Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor. Eur J Cancer. 2003; 39: 184-91.