Ca. Bladder.pptx

Lecture notes for medical students

1. Tips on using my ppt. You can freely download, edit, modify and put your name etc. Don’t be concerned about number of slides. Half the slides are blanks except for the title. First show the blank slides (eg. Aetiology ) > Ask students what they already know about ethology of today's topic. > Then show next slide which enumerates aetiologies. At the end rerun the show – show blank> ask questions > show next slide. This will be an ACTIVE LEARNING SESSION x three revisions. Good for self study also . Good for self study also. Display blank slide> Think what you already know about this > Read next slide . See notes for bibliography.

2. Learning Objectives

3. Learning Objectives Introduction & History Relevant Anatomy, Physiology Aetiology Pathophysiology Pathology Classification Clinical Features Investigations Management Prevention Guidelines Take home messages

4. Introduction & History.

5. Introduction & History. Bladder cancer is a common urologic cancer that has the highest recurrence rate of any malignancy. The most common type is urothelial carcinoma (UC). Other types squamous cell and adenocarcinomas.

6. Relevant Anatomy

7. Relevant Anatomy Arises in urothelium - transitional epithelium. I t lines urinary ducts Multilayered - renal calyxes (2 cell layers ), ureters (3 to 5 cell layers ), urethra (4 to 5 cell layers) and urinary bladder (up to 6 cell layers).

8. Relevant Anatomy The bladder is lined by epithelial cells that are somewhere in between the thick layers of squamous cells and the single layer of tall cells of glandular epithelia . Logically, these cells are called transitional cells because  they represent a transition between these two disparate epithelial cell types .

9. Aetiology

10. Aetiology Idiopathic Congenital/ Genetic Nutritional Deficiency/excess Traumatic Infections /Infestation Autoimmune Neoplastic (Benign/Malignant) Degenerative / lifestyle Iatrogenic Psychosomatic Poisoning/ Toxins/ Drug induced

11. Aetiology Idiopathic Congenital/ Genetic Nutritional Deficiency/excess Traumatic Infections /Infestation Autoimmune Neoplastic (Benign/ Malignant ) Degenerative / lifestyle Iatrogenic Psychosomatic Poisoning/ Toxins/ Drug induced

12. Aetiology of Aetiology Idiopathic Congenital/ Genetic Nutritional Deficiency/excess Traumatic Infections /Infestation Autoimmune Neoplastic (Benign/Malignant) Degenerative / lifestyle Iatrogenic Psychosomatic Poisoning/ Toxins/ Drug induced

13. Risk Factors

14. Risk Factors Up to 80% of bladder cancer cases are associated with environmental exposure. Upto 50% bladder cancer is due to smoking. Tobacco smoking nitrosamine, 2-naphthylamine, and 4-aminobiphenyl are possible carcinogenic agents found in cigarette smoke.. Workers exposed to aromatic amines , polycyclic aromatic hydrocarbons and heavy metals.

15. Risk Factors who work with organic chemicals and dyes: Beauticians Dry cleaners Painters Paper production workers Rope-and-twine industry workers Dental workers Physicians Barbers

16. Risk Factors People living in urban areas are also more likely to develop bladder cancer . Arsenic exposure Radiation treatment of the pelvis Chemotherapy with cyclophosphamide

17. Risk Factors for SCC Long-term indwelling catheters - A 16- to 20-fold increase in the risk of developing SCC Schistosoma haematobium  infection Bladder diverticula BCG treatment for CIS has been reported to lead to development of SCC. Bladder exstrophy Urachal remnants

18. Risk Factors No convincing evidence exists for a hereditary factor Coffee consumption does not increase the risk of developing bladder cancer. Artificial sweeteners (eg, saccharin, cyclamate) and bladder cancer;

19. Pathophysiology

20. Pathophysiology Urothelial carcinoma (UC ) initiates by carcinogens excreted in urine. SCC – Chronic irritation.

21. Pathophysiology Bladder cancer is often described as a polyclonal field change defect with frequent recurrences due to a heightened potential for malignant transformation . Urothelial carcinoma (UC) arises from stem cells that are adjacent to the basement membrane of the epithelial surface.

22. Pathophysiology Important early molecular events- somatic mutations in- Fibroblast growth receptor3 (FGFR-3) noninvasive Tumor protein p53 (TP53) and invasive pathways Loss of heterozygosity (LOH) on chromosome 9.

23. Pathology

24. Pathology The most common type is urothelial carcinoma (UC). Other types squamous cell and adenocarcinomas. Growth patterns: Papillary (70%) Sessile Mixed Nodular

25. Classification

26. Classification Non–muscle-invasive bladder cancer  Muscle-invasive bladder cancer  The current WHO/International Society of Urological Pathology (ISUP) system classifies bladder cancers as low grade or high grade.

27. Staging

28. TNM Classification T

29. TNM Classification TX - T0 - Tis - T1 - T2 - T3 - T4 -

30. TNM Classification CIS - Carcinoma in situ, high-grade dysplasia, confined to the epithelium Ta - Papillary tumor confined to the epithelium T1 - Tumor invasion into the lamina propria T2 - Tumor invasion into the muscularis propria : T2a, superficial muscularis propria ; T2b, deep muscularis propria T3 - Tumor involvement of the perivesical fat: T3a, microscopic invasion; T3b, macroscopic invasion T4 - Tumor involvement of adjacent organs: T4a, invasion of prostatic stroma , seminal vesicles, uterus, or vagina; T4b, invasion of pelvic or abdominal wall

31. TNM Classification N- Regiona l lymph nodes

32. TNM Classification N- Regiona l lymph nodes NX - N0 - N1 - N2 N3

33. TNM Classification N- Regiona l lymph nodes N0: No regional lymph node metastasis N1: Metastasis in a single lymph node in true pelvis N2: Metastasis in multiple regional lymph nodes in true pelvis N3: Metastasis in common iliac  lymph node(s ).

34. TNM Classification M- Metastasis- MX - M0 - M1 -

35. TNM Classification M- Metastasis- M0: No distant metastsis M1a: Non regional lymph nodes M1b: Other distant metastasis.

36. Clinical Features

37. Clinical Features Demography Symptoms Signs Prognosis Complications

38. Demography

39. Demography Incidence & Prevalence Geographical distribution. Race Age Sex Socioeconomic status Temporal behaviour

40. Demography Incidence & Prevalence -

41. Incidence & Prevalence- Bladder cancer is the fourth most common cancer in men in the United States Demogrphy

42. Geographical distribution. Demography

43. Demography Geographical distribution.  In industrialized countries, 90% of bladder cancers are TCC . In developing countries—particularly in the Middle East and Africa—the majority of bladder cancers are SCCs, and most of these cancers are secondary to  Schistosoma haematobium  infection. 

44. Demography Race.

45. Demography Race. The incidence of bladder cancer is twice as high in white men as in black men in the United States.

46. Demogrphy Age

47. Demography Age The incidence of bladder cancer increases with age, with the median age at diagnosis being 73 years; bladder cancer is rarely diagnosed before age 40 years.

48. Demography Sex

49. Demography Sex 3 times more common in men than in women.

50. Symptoms

51. Symptoms 7 warning signals of cancer Change in bowel or bladder habits. A sore that does not heal. Unusual bleeding or discharge. Thickening or lump in the breast or elsewhere. Indigestion or difficulty in swallowing. Obvious change in a wart or mole. Nagging cough or hoarseness.

52. Symptoms 7 warning signals of cancer Change in bowel or bladder habits . A sore that does not heal. Unusual bleeding or discharge. Thickening or lump in the breast or elsewhere. Indigestion or difficulty in swallowing. Obvious change in a wart or mole. Nagging cough or hoarseness.

53. Symptoms Painless gross hematuria   bladder cancer unless prooved otherwise. Irritative bladder symptoms (eg, dysuria, urgency, frequency of urination ) Pelvic or bony pain, lower-extremity edema, or flank pain - In patients with advanced disease Palpable mass on physical examination - Rare in superficial bladder cancer

54. Signs

55. Signs General Examination Systemic Examination Local Examination

56. Signs Local Examination

57. Signs Local Examination- Non ̶ muscle-invasive bladder cancer is typically not found during a physical examination.  In rare cases, a mass is palpable during abdominal, pelvic, rectal, or bimanual examination.  Attention to the anterior vaginal wall in women and the prostate in men may reveal findings that suggest local extension of bladder cancer.

58. Prognosis

59. Prognosis Morbidity Mortality rate 5 year survival in Malignancy

60. Prognosis The recurrence rate for superficial TCC of the bladder is high. Non–muscle-invasive bladder cancer has a good prognosis, with 5-year survival rates of 82-100 %. Prognosis for patients with metastatic urothelial cancer is poor,

61. Investigations

62. Investigations Laboratory Studies Routine Special Imaging Studies Tissue diagnosis Cytology FNAC Histology Germ line Testing and Molecular Analysis Diagnostic Laparotomy.

63. Investigations in Malignancy

64. Investigations in Malignancy For diagnosis For staging For Screening For Monitoring

65. Diagnostic Studies

66. Diagnostic Studies Laboratory Studies Urinalysis with microscopy Urine culture to rule out infection, if suspected Voided urinary cytology with Fluorescence in situ hybridization (FISH ). Bladder washings can be obtained by placing a catheter into the bladder and vigorously irrigating with saline (ie, barbotage ). Urinary tumor marker testing

67. Diagnostic Studies Urinary tumor marker testing Over 30 urinary biomarkers have been reported for use in bladder cancer diagnosis, but only a few are commercially available.   None have been accepted for diagnosis or follow-up in routine urologic practice or in guidelines.

68. Diagnostic Studies Cystoscopy The primary modality for the diagnosis of bladder carcinoma Permits biopsy and resection of papillary tumors

69. Diagnostic Studies Imaging Studies X-Ray USG CT Angiography MRI Endoscopy Nuclear scan

70. Diagnostic Studies Imaging Studies X-Ray USG CT – CECT abdomen,   CT urography Angiography MRI Endoscopy- Cystoscopy Nuclear scan

71. Differential Diagnosis

72. Differential Diagnosis Urinary Tract Infection (UTI) and Cystitis Hemorrhagic Cystitis: Noninfectious Nephrolithiasis Renal Cell Carcinoma Renal Transitional Cell Carcinoma Ureteral Trauma

73. Management

74. Management Non–muscle-invasive bladder cancer carcinoma in situ [CIS] -transurethral resection of bladder tumor (TURBT) with postoperative dose of intravesical chemotherapy and periodic cystoscopy. Muscle-invasive - Radical cystoprostatectomy in men Radical cystectomy with anterior pelvic exenteration in women Bilateral pelvic lymphadenectomy (PLND), standard or extended

75. Management Creation of a urinary diversion (eg, ileal conduit, Indiana pouch, orthotopic bladder substitution ). Neoadjuvant chemotherapy - May improve cancer-specific survival Trimodality therapy- TURBT followed by concurrent radiation therapy systemic chemotherapy.

76. Chemotherapeutic regimens

77. Chemotherapeutic regimens Methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (MVAC) Gemcitabine and cisplatin (GC)

78. Targeted Therapy Atezolizumab Nivolumab Avelumab Pembrolizumab Erdafitinib , 

79. Prevention

80. Prevention Screening Risk Reduction Cigarette smoking occupational exposure to carcinogens, with a recommendation that workers be informed of the risk and protective measures taken . Aromatic hydrocarbons - common in metal processing Aromatic amines - used in dyes N-nitrosamines - found in rubber and tobacco Formaldehyde

81. Guidelines American Urological Association/Society of Urological Oncology (AUA/SUO) European Association of Urology (EAU) European Society for Medical Oncology (ESMO) National Comprehensive Cancer Network (NCCN)

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