A population-based cohort study examining the association of documented bladder diverticulum and bladder cancer risk in urology patients

Autoři: Chu-Wen Fang aff001;  Vivian Chia-Rong Hsieh aff002;  Steven Kuan-Hua Huang aff001;  I-Ju Tsai aff003;  Chih-Hsin Muo aff003;  Shih-Chi Wu aff004
Působiště autorů: Division of Urology, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan aff001;  Department of Health Services Administration, China Medical University, Taichung, Taiwan aff002;  Management Office for Health Data, China Medical University and Hospital, Taichung, Taiwan aff003;  Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan aff004;  Trauma and Emergency Center, China Medical University Hospital, Taichung, Taiwan aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222875



Studies have shown a high risk of tumor development within a bladder diverticulum (BD). We were interested in the relationship between BD and the development of bladder cancer. Herein, we attempted to investigate whether there exists an association between documented BD and subsequent risk of bladder cancer.


We identified 10,662 hospitalized urology patients, including 2,134 documented BD patients (study cohort) and 8,528 non-BD subjects (comparison cohort) from Taiwan’s National Health Insurance database. Only urology patients were enrolled in the study to minimize selection bias. The two cohorts were frequency-matched 1:4 by age, sex and index-year. Patients with less than one year of follow-up were excluded to avoid inverting cause and effect. Risks of developing bladder cancer were estimated using the Cox proportional hazard regression model.


There was an increased bladder cancer risk in the documented BD patients. The incidence of bladder cancer in documented BD patients was 2.60-fold higher than that in the comparison group, and the overall risk-factor-adjusted hazard ratio was 2.63 (95% CI, 1.74–3.97). Moreover, stratified analysis by sex also showed that documented BD patients were at higher risk of subsequent bladder cancer than the comparison cohort. The effect of BD on the risk of bladder cancer was higher in males than in females and was more profound in patients without comorbidities than in those with comorbidities.


In this population-based longitudinal study, urology patients with documented BD might have an elevated risk of subsequent bladder cancer. Based on the limitations of the retrospective study design, further studies are required.

Klíčová slova:

Bladder – Bladder cancer – Cancer detection and diagnosis – Carcinomas – Chronic kidney disease – Taiwan – Urine – Urology


1. Ploeg M, Aben KK, Kiemeney LA. The present and future burden of urinary bladder cancer in the world. World J Urol 2009; 27:289. doi: 10.1007/s00345-009-0383-3 19219610

2. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67:7–30. doi: 10.3322/caac.21387 28055103

3. Marcos-Gragera R, Mallone S, Kiemeney LA, et al. Urinary tract cancer survival in Europe 1999–2007: Results of the population-based study EUROCARE-5. Eur J Cancer. 2015 Oct; 51(15]:2217–2230. doi: 10.1016/j.ejca.2015.07.028 26421824

4. Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013; 63(2]:234–41. doi: 10.1016/j.eururo.2012.07.033 22877502

5. Walker NF, Gan C, Olsburgh J, et al. Diagnosis and management of intradiverticular bladder tumours. Nat Rev Urol. 2014 Jul; 11(7]:383–90. doi: 10.1038/nrurol.2014.131 24934450

6. Kelalis PP, McLean P. The treatment of diverticulum of the bladder. J Urol 1967; 98:349–52. doi: 10.1016/s0022-5347(17)62888-x 4963798

7. Uemura K, Namura K, Umemoto S, et al. A Case of Squamous Cell Carcinoma in Bladder Diverticulum Producing Granulocyte Colony Stimulating Factor. Hinyokika Kiyo. 2017 May; 63(5]:211–215. doi: 10.14989/ActaUrolJap_63_5_211 28625029

8. El Abiad Y, Bakloul F. Squamous cell carcinoma in a giant bladder diverticulum. Pan Afr Med J. 2015 Apr 16; 20:378. doi: 10.11604/pamj.2015.20.378.6765 26185568

9. Fu LY, Adeniran AJ. Adenocarcinoma Arising from a Bladder Diverticulum. J Urol. 2015 Aug; 194(2]:527–8. doi: 10.1016/j.juro.2015.05.033 25986516

10. Raheem OA, Besharatian B, Hickey DP. Surgical management of bladder transitional cell carcinoma in a vesicular diverticulum: case report. Can Urol Assoc J. 2011 Aug; 5(4]:E60–4 21806896

11. Dong WX, Ping YX, Liang WC, et al. Small cell carcinoma of the urinary bladder diverticulum: a case report and review of the literature. J Cancer Res Ther. 2013 Jan-Mar; 9(1]:151–3. doi: 10.4103/0973-1482.110372 23575101

12. Abou Ghaida RR, Saoud RM, Bulbul M. Primary osteosarcoma in a bladder diverticulum. Can J Urol. 2014 Aug; 21(4]:7393–5. 25171286

13. Tseng CH. Diabetes and risk of bladder cancer: a study using the National Health Insurance database in Taiwan. Diabetologia. 2011 Aug; 54(8):2009–15. doi: 10.1007/s00125-011-2171-z 21544514

14. Lo SF, Chang SN, Muo CH, Chen SY, Liao FY, Dee SW, Chen PC, Sung FC. Modest increase in risk of specific types of cancer types in type 2 diabetes mellitus patients. Int J Cancer. 2013 Jan 1; 132(1):182–8. doi: 10.1002/ijc.27597 22510866

15. Bartsch GC, Kuefer R, Gschwend JE, et al. Hydronephrosis as a prognostic marker in bladder cancer in a cystectomy-only series. Eur Urol. 2007 Mar; 51(3):690–7; discussion 697–8. doi: 10.1016/j.eururo.2006.07.009 16904815

16. Lin HY, Wang SZ, Chen JX, et al. The prognostic value of hydronephrosis in bladder cancer treated by radical cystectomy. Urologia. 2011 Jan-Mar; 78(1):17–21. 21452155

17. Freedman ND, Silverman DT, Hollenbeck AR, Schatzkin A, Abnet CC. Association between smoking and risk of bladder cancer among men and women. JAMA. 2011 Aug 17; 306(7):737–45.2 21846855

18. Rink M, Crivelli JJ, Shariat SF, et al. Smoking and Bladder Cancer: A Systematic Review of Risk and Outcomes. Eur Urol Focus. 2015 Aug; 1(1):17–27. doi: 10.1016/j.euf.2014.11.001 28723350

19. Kobatake K, Hayashi T, Black PC, et al. Chronic kidney disease as a risk factor for recurrence and progression in patients with primary non-muscle-invasive bladder cancer. Int J Urol. 2017 Aug; 24(8):594–600. doi: 10.1111/iju.13389 28734027

20. Li CE, Chien CS, Chuang YC, et al. Chronic kidney disease as an important risk factor for tumor recurrences, progression and overall survival in primary non-muscle-invasive bladder cancer. Int Urol Nephrol. 2016 Jun; 48(6):993–9. doi: 10.1007/s11255-016-1264-5 26995008

21. Matsumoto S, Shimizu N, Hanai T, et al. Bladder outlet obstruction accelerates bladder carcinogenesis. BJU Int 2009, 103:1436–1439. doi: 10.1111/j.1464-410X.2008.08261.x 19076130

22. Sarma AV, Wei JT. Clinical practice. Benign prostatic hyperplasia and lower urinary tract symptoms. N Engl J Med. 2012; 367(3]:248–57 doi: 10.1056/NEJMcp1106637 22808960

23. Zhou J, Kelsey KT, Smith S, et al. Lower Urinary Tract Symptoms and Risk of Bladder Cancer in Men: Results from the Health Professionals Follow-Up Study. Urology. 2015; 85(6]:1312–1318. doi: 10.1016/j.urology.2015.02.024 25863833

24. Lowe FC, Goldman SM, Oesterling JE. Computerized tomography in evaluation of transitional cell carcinoma in bladder diverticula. Urology 1989;34:390–395 doi: 10.1016/0090-4295(89)90451-2 2595887

25. Shinai T, Anai M, Sakata T, et al. Primary carcinomas of urinary bladder diverticula. Acta Pathol Jpn 1984; 34:417–424. doi: 10.1111/j.1440-1827.1984.tb07570.x 6430029

26. Serrano M, Blasco MA. Cancer and ageing: convergent and divergent mechanisms. Nat Rev Mol Cell Biol. 2007; 8:715–722. doi: 10.1038/nrm2242 17717516

27. Toren Finkel T, Serrano M & Blasco MA. The common biology of cancer and ageing. Nature 448, 767–774. doi: 10.1038/nature05985 17700693

28. Tsai MH, Hsu CY, Lin MY, et al. Incidence, Prevalence, and Duration of Chronic Kidney Disease in Taiwan: Results from a Community-Based Screening Program of 106,094 Individuals. Nephron. 2018; 140(3):175–184. doi: 10.1159/000491708 30138926

29. Wen CP, Cheng TY, Tsai MK et al. All‐cause mortality attributable to chronic kidney disease: A prospective cohort study based on 462 293 adults in Taiwan. Lancet. 2008; 371: 2173–82. doi: 10.1016/S0140-6736(08)60952-6 18586172

30. Kuo HW, Tsai SS, Tiao MM, Yang CY. Epidemiological features of CKD in Taiwan. Am. J. Kidney Dis. 2007; 49: 46–55. doi: 10.1053/j.ajkd.2006.10.007 17185145

31. Hsu CC, Hwang SJ, Wen CP et al. High prevalence and low awareness of CKD in Taiwan: A study on the relationship between serum creatinine and awareness from a nationally representative survey. Am. J. Kidney Dis. 2006; 48: 727–38. doi: 10.1053/j.ajkd.2006.07.018 17059992

32. Chien CC, Han MM, Chiu YH, et al. Epidemiology of cancer in end-stage renal disease dialysis patients: a national cohort study in Taiwan. J Cancer. 2017 Jan 1; 8(1):9–18. doi: 10.7150/jca.16550 28123593

33. Fang CW, Liao CH, Wu SC, et al. Association of benign prostatic hyperplasia and subsequent risk of bladder cancer: an Asian population cohort study. World J Urol. 2018 Jun; 36(6):931–938. doi: 10.1007/s00345-018-2216-8 29427001

34. Melekos MD, Asbach HW, Barbalias GA: Vesical diverticula: etiology, diagnosis tumorgenesis and treatment. Analysis of 74 cases. Urology 1987; 30: 453–457. doi: 10.1016/0090-4295(87)90378-5 3118548

35. Faysal MH, Freiha FS. Primary neoplasm in vesical diverticula: A report of 12 cases. Br J Urol 1981; 53:141–3. doi: 10.1111/j.1464-410x.1981.tb03153.x 6786409

36. Golijanin D, Yossepowitch O, Beck SD, et al. Carcinoma in a bladder diverticulum: presentation and treatment outcome. J Urol. 2003 Nov; 170(5]:1761–4. doi: 10.1097/01.ju.0000091800.15071.52 14532771

37. Fox M, Power RF, Bruce AW. Diverticulum of the bladder: Presentation and evaluation of treatment of 115 cases. Br J Urol 1962; 34:286–98. doi: 10.1111/j.1464-410x.1962.tb09459.x 13959030

38. Haecker A, Riedasch G, Langbein S, et al. Diverticular carcinoma of the urinary bladder: diagnosis and treatment Problems. A case report. Med Princ Pract 2005; 14:121–4. doi: 10.1159/000083925 15785107

39. Lawrence WW (Ed]: Current Surgical Diagnosis and treatment, 10th e Englewood Cliffs, New Jersey, Prentice-Hall, 1994; 952–954.

40. Prakash Rajini T, Bhardwaj AK, Jayanthi V, Rao PK, Singh G. Urinary bladder diverticulum and its association with malignancy: an anatomical study on cadavers. Rom J Morphol Embryol 2010; 51:543–5. 20809034

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