Bladder cancer Epidemiology and Etiology

Bladder cancer is a disease of urinary bladder in which cells grow abnormally and have the potential to spread to other parts of the body. This is one of four parts of presentations on Bladder cancer. Please do go through the rest of the presentations too.

1. carcinoma urinary Bladder EPIDEMIOLOGY & ETIOLOGY By Dr. Muhammad Saifullah Post-Graduate Resident (FINAL YEAR) Department of Urology & Renal Transplantation Allied Hospital, Faisalabad.

2. Most ominous sign in field of Urology is ….. HEMATURIA especially PAINLESS…

3. HEMATURIA….. COMMON CAUSES Urinary tract infection  with bacteria. The vast majority of UTIs are caused by Escherichia coli, with a smaller percentage due to  Klebsiella pneumonia and Staphylococcus saprophyticus Nephrolithiasis : stones in the kidney, bladder or ureter Polycystic kidney disease .

4. HEMATURIA….. COMMON CAUSES Benign prostatic hyperplasia , in older men, especially those over 50. Vigorous exercise . Trauma

5. HEMATURIA….. RARE CAUSES Glomerular bleeding: e.g.:  IgA nephropathy  ("Berger's disease"),  Alport syndrome, thin basement membrane disease Sickle cell disease Schistosomiasis  (caused by  Schistosoma haematobium ) - a major cause for hematuria in many African and Middle-Eastern countries.

6. HEMATURIA….. RARE CAUSES Recent instrumentation of the urinary tract Prostatitis Urethritis Arteriovenous malformation  of the kidney (rare, but may impress like renal cell carcinoma on scans as both are highly vascular)

7. HEMATURIA….. VERY RARE CAUSES Vesical varices  may rarely develop secondary to obstruction of the inferior vena cava. Allergy  may cause episodic gross hematuria in children. Left renal vein hypertension, also called "nutcracker phenomenon" or "nutcracker syndrome.

8. HEMATURIA….. VERY RARE CAUSES Ureteral Pelvic Junction Obstruction . Athletic nephritis  secondary to strenuous exercise

9. HEMATURIA….. COMMON CAUSES CARCINOMA OF URINARY TRACT According to Oxford handbook of Urology (3 rd Edition) Visible hematuria ….. Urothelial Carcinoma 20-25% Microscopic hematuria ….. Urothelial Carcinoma 5-10%

10. HEMATURIA….. CAUSES

11. INTRODUCTION Rapid creation of abnormal cells that grow beyond their usual boundaries, and which can then invade adjoining parts of the body and spread to other organs. Uncontrolled growth and spread of cells…… CANCER

12. INTRODUCTION It can involve any organ of the body but whenever the affected organ is bladder, Bladder Carcinoma. Bladder cancer is the second most common cancer of the genitourinary tract.

13. EPIDEMIOLOGY….. EAU Bladder cancer (BC) is the 7th most commonly diagnosed cancer in the male population worldwide, while it drops to 11th when both genders are considered. The worldwide age- standardised incidence rate (per 100,000 person/years) is 9.0 for men and 2.2 for women.

14. EPIDEMIOLOGY….. EAU Worldwide, BC age- standardised mortality rate (per 100,000 person/years) was 3.2 for men vs. 0.9 for women in 2012. 75% of patients with BC present with a disease confined to the mucosa (stage Ta,CIS ) or submucosa (T1). They have a high prevalence due to long-term survival in many cases and lower risk of cancer- specific mortality compared to T2-4 tumours .

15. EPIDEMIOLOGY Bladder cancer is the 9th most common cancer worldwide, with 357,000 cases recorded in 2002. Bladder cancer is the 13th most common cause of death, accounting for 145,000 deaths worldwide. Sixty-three percent of all bladder cancer cases occur in developed countries, with 55% from North America and Europe.

16. EPIDEMIOLOGY The American Cancer Society estimates that 76,960 new cases of bladder cancer will be diagnosed in the United States in 2016 and that 16,390 people will die of the disease. Bladder cancer is the fourth most common cancer in men in the United States, after prostate, lung, and colorectal cancer, but it is not among the top 10 cancers in women.

17. EPIDEMIOLOGY The American Cancer Society estimates that 76,960 new cases of bladder cancer will be diagnosed in the United States in 2016 and that 16,390 people will die of the disease. Bladder cancer is the fourth most common cancer in men in the United States, after prostate, lung, and colorectal cancer, but it is not among the top 10 cancers in women.

18. EPIDEMIOLOGY The histologic cell type of bladder cancer is very geographically dependent, but urothelial cancer is the most common. In North America and Europe, 95% to 97% of cases are urothelial carcinoma.

19. EPIDEMIOLOGY In Africa 60% to 90% are urothelial and 10% to 40% are squamous cell carcinoma. Egypt has the highest rate of squamous cell carcinoma because of the endemic infections with Schistosoma species.

20. etiology

21. ETIOLOGY Bladder cancer is caused by genetic abnormalities and external risk factors, including: Carcinogen exposure Nutritional factors Fluid intake Alcohol

22. ETIOLOGY Inflammation Infection Chemotherapy Radiation Artificial sweeteners.

23. COMMONEST CAUSE FOR BLADDER CARCINOMA…..?

24. ETIOLOGY Tobacco smoking is the most important risk factor for Bladder Carcinoma….. approximately 50% of cases. Tobacco smoke contains aromatic amines and polycyclic aromatic hydrocarbons, which are renally excreted. 65% Cases in men and 20-30% Cases in women (Smith Urology – 18 th Edition).

25. ETIOLOGY Tobacco smoking The causative agents are thought to be alpha- and betanaphthylamine , which are secreted into the urine of smokers. The risk of bladder appears to decrease after smoking cessation but may not reach the levels of never smokers.

26. ETIOLOGY….. CAMPBELL If a person smokes 1 to 9 cigarettes versus more than 21 cigarettes per day, the relative risk of bladder cancer is 1.5 versus 5.4, respectively. If a person smokes 1 to 10 years versus more than 40 years, the relative risk of bladder cancer is 1.2 versus 3.0, respectively.

27. ETIOLOGY….. CAMPBELL If a person smokes more than 60 years, they have a sixfold increased risk of developing urothelial cancer compared with a nonsmoker.

28. ETIOLOGY Occupational exposure to aromatic amines, polycyclic aromatic hydrocarbons and chlorinated hydrocarbons is the second most important risk factor for Bladder Carcinoma….. 10% of all cases. This type of occupational exposure occurs mainly in industrial plants which process paint, dye, metal, leather, rubber and petroleum products. Long latency period of 10 to 20 years between the industrial exposure and the formation of the bladder cancer.

29. ETIOLOGY Occupational exposure 15-35% Cases in men and 1-6% cases in women. (Smith Urology-18 th Edition). Environmental carcinogens can enter the system and cause bladder cancer from inhalation or through skin absorption.

30. ETIOLOGY Occupational exposure The overall increased risk of bladder cancer formation in industrial workers is 30%, with agriculture workers having the lowest and rubber workers the highest risk of bladder cancer formation.

31. ETIOLOGY….. Occupation

32. ETIOLOGY….. EAU Nutritional factors….. Fruits and vegetables—specifically citrus, apples, berries, tomatoes, carrots, and cruciferous vegetables—contain several active compounds that are important in detoxification.

33. ETIOLOGY….. nutrition These compounds include polyphenols , antioxidants, and enzymes that modulate the detoxification of nitrous amines and can prevent DNA adduct formation and oxidative damage. Micronutrients associated with a preventive effect on urothelial cancer formation are mainly antioxidants, including vitamins A, C, and E; selenium; and zinc .

34. ETIOLOGY….. nutrition These compounds include polyphenols , antioxidants, and enzymes that modulate the detoxification of nitrous amines and can prevent DNA adduct formation and oxidative damage. Occurrence of urothelial cancer is moderately higher in COFFEE AND TEA DRINKERS , but this may be compounded by smoking or other dietary factors associated with people who drink coffee or tea.

35. ETIOLOGY….. nutrition nutrition….. A diet rich in fruits and vegetables is protective against bladder cancer formation.

36. ETIOLOGY….. EAU Fluid intake….. F luid intake leads to less micturition and higher concentrations of potential carcinogens in the urine and thus an increased risk of bladder cancer.

37. ETIOLOGY….. campbell gender….. Males are 3 to 4 times more likely to develop bladder cancer than females, presumably because of an increased prevalence of smoking and exposure to environmental toxins.

38. ETIOLOGY….. campbell heredity….. First-degree relatives of patients with bladder cancer have a twofold increased risk of developing urothelial cancer themselves . There is a hereditary component to bladder cancer formation, probably through low- penetrance genes (NAT-2 and the GSTM1 polymorphisms) that increase the susceptibility of carcinogens.

39. ETIOLOGY….. campbell Chemotherapy….. cYlophosphamide . The risk of bladder cancer formation is linearly related to the duration and intensity of cyclophosphamide treatment, supporting a causative role. Phosphoramide mustard is the primary mutagenic metabolite that causes bladder cancer in patients exposed to cyclophosphamide .

40. ETIOLOGY….. infection Schistosomiasis , a chronic endemic cystitis, based on recurrent infection with a parasitic trematode , is also a cause of Bladder Cancer. The Schistosoma ova are deposited in the wall of the bladder  C hronic inflammation  Converts the urothelium to a squamous cell epithelium.

41. ETIOLOGY….. shistosomiasis Squamous cell epithelium has a much greater proliferation rate, and, with the presence of chronic inflammation, over time this greater proliferation rate leads to cancer formation.

42. Shistosoma hematobium

43. ETIOLOGY….. infection HPV infection , There is a possible link between human papillomavirus (HPV) and urothelial cancer formation. HPV encodes two oncoproteins , E6 and E7. E6 interacts with TP53, which has a role in bladder cancer progression and formation. Still under study.

44. ETIOLOGY….. Campbell Analgesic abuse , Acetaminophen is the active metabolite of phenacetin , a commonly used antipyretic and analgesic. Consumptions of large quantities of acetaminophen or phenacetin (5 to 15 kg during a10-year period) have been associated with an increased risk of bladder cancer.

45. ETIOLOGY….. Campbell Analgesic abuse , Kaye and colleagues (2001) performed a nested match case–controlled study and found no association between acetaminophen or other nonsteroidal anti-inflammatory drug ingestion and bladder cancer

46. ETIOLOGY….. EAU Chlorination….. of drinking water and subsequent levels of trihalomethanes are potentially carcinogenic. Exposure to arsenic in drinking water increases risk.

47. ETIOLOGY….. EAU Exposure to ionizing radiation is connected with increased risk.

48. Take home message…..