- Volume 17 Issue 1
Background: Epidemiological evidence indicates that individuals with diabetes mellitus (DM) may have a modestly increased risk of bladder cancer. In the present study, we aimed to show any association between DM and risk of metastasis in patients with non-muscle-invasive bladder cancer (NMIBC). Materials and Methods: We retrospectively analyzed 698 patients between January 2007 and December 2014 who were diagnosed with and underwent transurethral resection of bladder tumors (TUR-BT). Comparisons of means was conducted by independent samples t test, and relations between categorical variables were investigated by non-parametric chi-square test. A p value of 0.05 was accepted as statistically significant in comparisons. Results: We analyzed 418 patients with non muscle invasive bladder cancer. 123 of whom were diabetic and 295 non-diabetic. In diabetic patients, 13 were N1 stage and 11 M1 stage. When compared with non diabetic patients that was statistically significant (p<0.001). TNM stages were more advanced in diabetic patients (p<0.001), but concurrent CIS (p=0.1) and squamous metaplasia did not significantly differ between diabetic and non-diabetic cases (p=1). Conclusions: Diabetic patients with non-muscle-invasive bladder cancer may suffer metastases earlier than expected although they are non invasive. Therefore such patients must be followed-up carefully and early cystectomy decision may be necessary. Further prospective studies with more patients are needed to confirm these findings.
Bladder cancer;diabetes mellitus;non-muscle-invasive;metastasis risk
- Aaronson S (1991). Growth factors and cancer. Sci, 254, 1146-53. https://doi.org/10.1126/science.1659742
- Amalinei C, Caruntu ID, Giusca SE, et al (2010). Matrix metalloproteinases involvement in pathologic conditions. Rom J Morphol Embryol, 51, 215-28.
- Attia N, Caprio S, Jones TW, et al (1999). Changes in free insulin-like growth factor-1 and leptin concentrations during acute metabolic decompensation in insulin withdrawn patients with type 1 diabetes. J Clin Endocrinol Metab, 84, 2324-8.
- Bischoff CJ, Clark PE (2009). Bladder cancer. Curr Opin Oncol, 21, 272-7. https://doi.org/10.1097/CCO.0b013e328329f184
- Boyle JG, Salt IP, McKay GA (2010). Metformin action on AMPactivated protein kinase, A translational research approach to understanding a potential new therapeutic target. Diabet Med, 27, 1097-106. https://doi.org/10.1111/j.1464-5491.2010.03098.x
- Brausi M, Collette L, Kurth K, et al (2002). EORTC genitourinary tract cancer collaborative group. variability in the recurrence rate at first follow-up cystoscopy after TUR in stage Ta T1 transitional cell carcinoma of the bladder, a combined analysis of seven EORTC studies. Eur Urol, 41, 523-31. https://doi.org/10.1016/S0302-2838(02)00068-4
- Chen HC, Chen CA, Guh JY, et al (2000). Altering expression of alpha3beta1 integrin on podocytes of human and rats with diabetes. Life Sci, 67, 2345-53. https://doi.org/10.1016/S0024-3205(00)00815-8
- Coughlin SS, Calle EE, Teras LR, et al (2004). Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol, 159, 1160-7. https://doi.org/10.1093/aje/kwh161
- Divrik RT, Sahin AF, Yildirim U, et al (2010). Impact of routine second transurethral resection on the long-term outcome of patients with newly diagnosed pT1 urothelial carcinoma with respect to recurrence, progression rate, and diseasespecific survival, a prospective randomised clinical trial. Eur Urol, 58, 185-90. https://doi.org/10.1016/j.eururo.2010.03.007
- Hong JH (2015). Early isolated bone metastases without local recurrence in non-muscle invasive bladder cancer. Int J Surg Case Rep, 10, 41-4. https://doi.org/10.1016/j.ijscr.2015.03.029
- Hwang EC, Kim YJ, Hwang IS, et al (2011). Impact of diabetesmellitus on recurrence and progression in patients with nonmuscle invasive bladder carcinoma, A retrospective cohort study. Int J Urol, 18, 769-76. https://doi.org/10.1111/j.1442-2042.2011.02845.x
- Jee SH, Ohrr H, Sull JW, et al (2005). Fastingserum glucose level and cancer risk in Korean men and women. JAMA, 293, 194-202. https://doi.org/10.1001/jama.293.2.194
- Larsson SC, Orsini N, Brismar K, et al (2006). Diabetes mellitus and risk of bladder cancer, a meta-analysis. Diabetologia, 49, 2819-23. https://doi.org/10.1007/s00125-006-0468-0
- Larsson SC (2008). Diabetes mellitus, body size and bladder cancer risk in a prospective study of Swedish men. Eur J Cancer, 44, 2655-60. https://doi.org/10.1016/j.ejca.2008.07.012
- Lipponen PK, Eskelinen MJ (1995). Reduced expression of E-cadherin is related to invasive disease and frequent recurrence in bladder cancer. J Cancer Res Clin Oncol, 121, 303-8 https://doi.org/10.1007/BF01209598
- MacKenzie T, Zens MS, Ferrara A, et al (2011). Diabetes and risk of bladder cancer, evidence from a case-control study in New England. Cancer, 117, 1552-6. https://doi.org/10.1002/cncr.25641
- Mamtani R, Pfanzelter N, Haynes K, et al (2014). Incidence of bladder cancer in patients with type 2 diabetes treated with metformin or sulfonylureas. Diabetes Care, 37, 1910-7. https://doi.org/10.2337/dc13-1489
- Mariappan P, Zachou A, Grigor KM (2010). Detrusor muscle in the first, apparently complete transurethral resection of bladder tumour specimen is a surrogate marker of resection quality, predicts risk of early recurrence, and is dependent on operator experience. Eur Urol, 57, 843-9. https://doi.org/10.1016/j.eururo.2009.05.047
- Plowman GD, Green JM, McDonald VL, et al (1981). The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumor-inhibitory activity. Mol Cell Biol, 10, 1969-81.
- Poulson J (1997). The management of diabetes in patients with advanced cancer. J Pain Symptom Manage, 13, 339-34. https://doi.org/10.1016/S0885-3924(96)00326-0
- Radinsky R (1991). Growth factors and their receptors in metastasis. Semin Cancer Biol, 2, 169-77.
- Richardson LC, Pollack LA (2005). Therapy insight, influence of type 2 diabetes on the development, treatment and outcomes of cancer. Nat Clin Pract Oncol, 2, 48-53. https://doi.org/10.1038/ncponc0062
- Rieken M, Xylinas E, Kluth L, et al (2013). Association of diabetes mellitus and metformin use with oncological outcomes of patients with non-muscle invasive bladder cancer. BJU Int, 112, 1105-12. https://doi.org/10.1111/bju.12448
- Rodel C, Grabenbauer GG, Kuhn R, et al (2002). Combinedmodality treatment and selective organ preservation in invasive bladder cancer, long-term results. J Clin Oncol, 20, 3061-71. https://doi.org/10.1200/JCO.2002.11.027
- Rucci N, Sanita P, Angelucci A (2011). Roles of metalloproteases in metastatic niche. Curr Mol Med, 11, 609-22. https://doi.org/10.2174/156652411797536705
- Sasaki Y1, Oi H, Oyama T, et al (2013). Non-muscle invasive bladder cancer with multiple bone metastasis without local invasion, a case report. Hinyokika Kiyo, 59, 669-72.
- Schenk-Braat, EA, Bangma, CH, (2005). Immunotherapy for superficial bladder cancer. Cancer Immunol Immunother, 54, 414-423. https://doi.org/10.1007/s00262-004-0621-x
- Siegel R, Naishadham D, Jemal A (2012). Cancer statistics, 2012. CA Cancer J Clin, 62, 10-29. https://doi.org/10.3322/caac.20138
- Stiles CD, Capone GT, Scher CD, et al (1979). Dual control of cell growth by somatomedins and platelet-derived growth factor. Proc Natl Acad Sci USA, 76, 1279-83. https://doi.org/10.1073/pnas.76.3.1279
- Sylvester RJ, van der Meijden AP, Oosterlinck W, et al (2006). Predicting recurrence and progression in individual patients with stage TaT1 bladder cancer using EORTC risk tables, a combined analysis of 2596 patients from seven EORTC trials. Eur Urol, 49, 466-77. https://doi.org/10.1016/j.eururo.2005.12.031
- Tripathi A, Folsom AR, Anderson KE (2002). Risk factors for urinary bladder carcinoma in postmenopausal women. the iowa women's health study. Cancer, 95, 2316-23. https://doi.org/10.1002/cncr.10975
- Tuncer M, Faydaci G, Altin G, et al (2014). Metastasis of nonmuscle- invasive bladder cancer into the thyroid gland, a literature review accompanied by a rare case. Korean J Urol, 55, 222-5. https://doi.org/10.4111/kju.2014.55.3.222
- Turati F, Polesel J, Di Maso M, et al (2015). Diabetes mellitus and the risk of bladder cancer, an Italian case-control study. Br J Cancer, 1-4.
- Vigneri P, Frasca F, Sciacca L, et al (2009). Diabetes and cancer. Endocr Relat Cancer, 16, 1103-23. https://doi.org/10.1677/ERC-09-0087
- Zeegers MP, Tan FE, Dorant E, et al (2000). The impact of characteristics of cigarette smoking on urinary tract cancer risk, a meta-analysis of epidemiologic studies. Cancer, 89, 630-9 https://doi.org/10.1002/1097-0142(20000801)89:3<630::AID-CNCR19>3.0.CO;2-Q
- Zhang T, Guo P, Zhang Y, et al (2013). The antidiabetic drug metformin inhibits the proliferation of bladder cancer cells in Vitro and in Vivo. Int J Mol Sci, 14, 24603-18. https://doi.org/10.3390/ijms141224603
- Zhou G, Myers R, Li Y, et al (2001). Role of AMP-activated protein kinase in mechanism of metforminaction. J Clin Invest, 108, 1167-74. https://doi.org/10.1172/JCI13505
- Association of metformin intake with bladder cancer risk and oncologic outcomes in type 2 diabetes mellitus patients vol.97, pp.30, 2018, https://doi.org/10.1097/MD.0000000000011596