Mide prekanseröz lezyonlarında klopidogrel kullanımının değerlendirilmesi: Kemopreventif etkisi var mı?

Abstract

Amaç: Mide maligniteleri kansere bağlı ölümlerin en sık üçüncü nedenidir. Aspirin ve klopidogrelin kolorektal kanser riskini azalttığı bildirilse de mide kanseri üzerindeki etkileri halen araştırılmaktadır. Bu çalışmanın amacı; klopidogrelin gastrik prekanseröz lezyonların gelişiminde etkisinin olup olmadığını belirlemektir. Gereç ve Yöntemler: Çalışma retrospektif vaka kontrol çalışması olarak tasarlandı. Çalışma Ocak 2021-Nisan 2023 tarihleri arasında Samsun Üniversitesi Samsun Eğitim ve Araştırma Hastanesi Gastroenteroloji Kliniğinde gerçekleştirildi. Dispepsi şikayeti nedeniyle üst GİS endoskopisi ve biyopsi incelemesi yapılan hastalar hastanenin elektronik veri sisteminden taranarak klopidogrel (89 hasta), düşük doz aspirin (ASA) (172 hasta), aspirin dışı non-steroid antiinflamatuar ilaç (NA-NSAID) (110 hasta) kullanıcıları ve antiplatelet kullanmayan kontrol grubu (110 hasta) olmak üzere 4 grup oluşturularak verileri kaydedildi. İstatistiksel analizler SPSS v20.0 ile yapıldı. Bulgular: Ortalama ilaç kullanım süresi klopidogrel için 2 yıl, ASA için 1,47 yıl ve NA-NSAID için 0,35 yıl idi. Peptik ülser görülme sıklığı kontrol grubunda %7,2, klopidogrel, ASA, NA-NSAİİ kullananlarda sırasıyla %38, %15,1, %49 idi (p<0,001). Gruplarda H. pylori enfeksiyonu sıklığı sırasıyla %61, %53,5, %40,1, %46,1 idi. ASA ile kontrol grubu arasında anlamlı fark vardı (p<0,001). Bağırsak metaplazisi sırasıyla %23,1, %29,5, %31,2, %23,1 oranında görüldü (p=0,291). Atrofik gastrit oranları sırasıyla %16,6, %35,2, %19,2, %29,3 idi (p=0,003). Displazi, mide kanseri ve yemek borusu kanseri açısından gruplar arasında fark gözlenmedi. Sonuç: Sonuçlarımıza göre klopidogrel, ASA ve NA-NSAID kullanımının prekanseröz lezyonları veya mide kanseri gelişimini önleyici etkisi gözlenmedi. Ancak bu ilaçların kullanımı ciddi gastroduodenal lezyonlarla ilişkilendirilmiştir.

Keywords

• Anahtar Kelimeler: Aspirin
• Klopidogrel
• mide kanseri
• mide kanserli lezyonlar

Evaluation of clopidogrel use on gastric precancerous lesions: Does it have chemopreventive effect?

Abstract

Aims: Gastric malignancies are the third most common cause of cancer-related deaths. Although aspirin and clopidogrel have been reported to reduce the risk of colorectal cancer, their effects on gastric cancer are still under investigation. In this study, we aimed to determine whether clopidogrel has an effect on the development of gastric precancerous lesions. Methods: The study was designed as a retrospective case-control study. The study was conducted between January 2021 and April 2023 in the Gastroenterology Clinic of Samsun University Samsun Training and Research Hospital. Patients who underwent upper GIS endoscopy and biopsy examination due to dyspeptic complaints were scanned from the electronic data system of the hospital and their data were recorded by forming 4 groups as clopidogrel (89 patients), low-dose aspirin (ASA) (172 patients), non-aspirin non-steroidal anti-inflammatory drug (NA-NSAID) users (110 patients) and control group without antiplatelet use (110 patients). Statistical analyses were accomplished with SPSS for Windows v20.0. Results: Mean duration of drug use was 2 years for clopidogrel, 1.47 years for ASA and 0.35 years for NA-NSAID. The incidence of peptic ulcer was 7.2% in the control group, 38%, 15.1%, 49% in clopidogrel, ASA, NA-NSAID users, respectively (p<0.001). The frequency of H. pylori infection in the groups was 61%, 53.5%, 40.1%, 46.1%, respectively. There was a significant difference between ASA and control group (p<0.001). Intestinal metaplasia was observed in 23.1%, 29.5%, 31.2%, 23.1%, respectively (p=0.291). Atrophic gastritis was 16.6%, 35.2%, 19.2%, 29.3%, respectively (p=0.003). No difference was observed between the groups in terms of dysplasia, gastric cancer and esophageal cancer. Conclusion: According to our results, no preventive effects of clopidogrel, ASA and NA-NSAID use on precancerous lesions or gastric cancer development were observed. However, the use of these drugs was associated with severe gastroduodenal lesions.

Keywords

• Aspirin
• Clopidogrel
• gastric cancer
• gastric cancerous lesions

References

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
2. Demirci H, Ozturk K, Tanoglu A, et al. Helicobacter pylori colonization density is an important risk factor for eradication therapy. J Gastrointestin Liver Dis. 2022;31(2):163-167.
3. Kaplan M, Tanoglu A, Duzenli T, Tozun AN. Helicobacter pylori treatment in Turkey: current status and rational treatment options. North Clin Istanb. 2019;7(1):87-94.
4. Kalkanlı Taş S, Kırkık D, Öztürk K, Tanoğlu A. Determination of B- and T- cell epitopes for Helicobacter pylori cagPAI: An in silico approach. Turk J Gastroenterol. 2020;31(10):713-720.
5. Ford AC, Yuan Y, Moayyedi P. Helicobacter pylori eradication therapy to prevent gastric cancer: systematic review and meta-analysis. Gut. 2020;69(12):2113-2121.
6. Algra AM, Rothwell PM. Efects of regular aspirin on long term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol. 2012;13(5):518-527.
7. Kim YL, Kim SY, Kim KJ, et al. Long-term low-dose aspirin use reduces gastric cancer incidence: a nationwide cohort study. Cancer Res Treat. 2016;48(2):798-805.
8. Bofei Li, Cheung KS, Wong IY, et al. Nonaspirin nonsteroidal anti-inflammatory drugs and gastric cancer risk after Helicobacter pylori eradication: a territory-wide study. Cancer. 2021;127(11):1805-1815.

9. Miguel RA, Luis A, Rodríguez GI, et al. Clopidogrel and low-dose aspirin, alone or together, reduce risk of colorectal cancer. Clin Gastroenterol Hepatol. 2019;17(10):2024-2033.
10. Tsai TJ, Lai KH, Hsu PI, et al. Upper gastrointestinal lesions in patients receiving clopidogrel anti-platelet therapy. J Formos Med Assoc. 2012;111(12):705-710.
11. Fork FT, Lafolie P, Toth E, Lindgarde F. Gastroduodenal tolerance of 75 mg clopidogrel versus 325 mg aspirin in healthy volunteers. A gastroscopic study. Scand J Gastroenterol. 2000;35(5):464-469.
12. Lanza FL. A review of gastric ulcer and gastroduodenal injury in normal volunteers receiving aspirin and other non-steroidal anti-inflammatory drugs. Scand J Gastroenterol Suppl. 1989;163:24-31.
13. Chan FK, Ching JY, Hung LC, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med. 2005;352(3):238-244.
14. Sinha M, Gautam L, Shukla PK, et al. Current perspectives in NSAID-induced gastropathy. Mediators Inflamm. 2013;2013:258209.
15. Wang D, Dubois RN. Prostaglandins and cancer. Gut. 2006; 55(1):115-122.
16. Cheung KS, Chan EW, Wong AYS, et al. Aspirin and risk of gastric cancer after Helicobacter pylori eradication: a territory-wide study. J Natl Cancer Inst. 2018;110(7):743-749.
17. Weltermann T, Schulz C, Macke L. Effect of frequently prescribed drugs on gastric cancer risk. Best Pract Res Clin Gastroenterol. 2021;50-51:101741.
18. Altayar O, Davitkov P, Shailja C, et al. AGA Technical review on gastric intestinal metaplasia - epidemiology and risk factors. Gastroenterology. 2020;158(3):732-744.
19. Song H, Ekheden IG, Zheng z, et al. Incidence of gastric cancer among patients with gastric precancerous lesions: observational cohort study in a low risk Western population. BMJ 2015;351:3867.
20. Sonnenberg A, Genta RM. Changes in the gastric mucosa with aging. Clin Gastroenterol Hepatol. 2015;13(13):2276-22781.
21. Ozdil K, Sahin A, Kahraman R, et al. Current prevalence of intestinal metaplasia and Helicobacter pylori infection in dyspeptic adult patients from Turkey. Hepatogastroenterology. 2010;57(104):1563-1566.
22. Kiyak M, Duzenli T. Helicobacter pylori colonization density may have an important role in the development of celiac disease. Turk J Acad Gastroenterol. 2023;22(1):6-12.
23. Nagata N, Niikura R, Sekine K, et al. Risk of peptic ulcer bleeding associated with Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs, low-dose aspirin, and antihypertensive drugs: a case-control study. J Gastroenterol Hepatol. 2015;30(2):292-298.
24. Köseoğlu H, Duzenli T, Sezikli M. Gastric neuroendocrine neoplasms: a review. World J Clin Cases. 2021;9(27):7973-7985.
25. Annibale B, Esposito G, Lahner E. A current clinical overview of atrophic gastritis. Expert Rev Gastroenterol Hepatol. 2020;14(2):93-102.
26. Clemens A, Strack A, Noack H. Anticoagulant-related gastrointestinal bleeding—could this facilitate early detection of benign or malignant gastrointestinal lesions? Ann Med. 2014;46(8):672-678.
27. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20(10):1161-1181.