1. Bladder Carcinoma
DR. Gehan Mohamed

2. Bladder Carcinoma
Definition: malignant tumor arising from the epithelial lining of the urinary bladder.
(N.B normal epithelial lining of urinary bladder is transitional epithelium but it can change to squamous epithelium or columnar type under the effect of continuous irritation by inflammation, or stone formation)

4. transitional epithelium (urothelium) lining the normal urinary Bladder.

6. Epidemiology of Bladder Carcinoma
Caucasians ~ 2x > African Americans > Hispanics & Asians
M:F = 3:1
age 40 : 60 years.

7. Risk Factors for Bladder Cancer
1- Genetics (eg, Retinoblastoma gene mutation which is tumor suppresor gene present on chromosome 13 undergo hereditary or aquired mutation so lost its function ).
2- Bladder birth defects eg. persistent urachus  increase risk for adenocarcinoma.
Urachus is a connection between belly button(umblicus) and bladder. Normally disappears before birth. If part of the connection remains, it could become cancerous. Cancers that start in the urachus are usually made up of malignant glandular cells and are called adenocarcinomas.
3- Pelvic radiation exposure
Cigarette smoking - #1 avoidable risk factor

8. Risk Factors for Bladder Cancer
4- Cigarette smoking (2-4x higher relative risk)
Some carcinogens in tobacco smoke are absorbed from lungs and get into blood. From there, they are filtered by kidneys and concentrated in urine. These chemicals in the urine damage the urothelial cells(transitional epithelium) that line the inside of the bladder  increase Carcinoma risk.
5-Cyclophosphamide A highly toxic, immunosuppressive, antineoplastic drug  9 fold increase risk
6- Arsenic
7- Occupational Exposures to chemicals: Polycyclic aromatic hydrocarbons, benzidine, benzene, exhaust from combustion gases. Al+3 workers; dry cleaners; manufacturers of preservatives, dye, rubber, & leather; pesticide applicators; painters; truck drivers; printers; machinists.
(N.B Low fluid intake increase exposure to any chemical carcinogens via decreased bladder emptying.)

9. Risk Factors for Bladder Cancer
8- Infections
Schistosoma haematobium (North Africa)  Increase risk for squamous & transitional cell Carcinoma.
Schistosoma haematobium  formation of carcinogenic substance N-nitroso compounds  increased risk for both squamous and transitional cell Carcinoma.
9- bladder stones  cause chronic irritation to the mucosa so increase risk for squamous cell metaplasia  Cancer.

10. Microscopic types of Bladder Canrcinoma
1- Transitional cell carcinoma (> 95%)
Flat – Do not grow toward the hollow part of the bladder.
Papillary (70%) – Grow toward the hollow part of the bladder.
2- Squamous cell (keratinizing) carcinoma (1-3%) on top of squamous metaplasia.
3- Adenocarcinoma (1-2%) .
4- Small cell carcinoma (< 1%)
5- spindle (sarcomatoid ) carcinoma
6-Mixed-histology (predominantly transitional cell with other types).

12. Papillary transitional cell carcinoma high grade

13. Transitional cell carcinoma

14. Infiltrating transitional cell carcinoma

15. Squamous metaplasia in bladder

16. Squamous cell carcinoma

17. Squamous cell carcinoma showing keratinized nests of squamous epithelium

18. Adenocarcinoma : tumor cells form glands with malignant criteria , and deeply infiltrating
Cytokeratin +

19. Sarcomatoid carcinoma

20. Diagnosis of bladder cancer
1- clinical picture
2- investigations to confirm diagnosis ,determine the histologic type, grade, and detect its extent.
3- immunohistochemistry using cytokeratin which is positive with malignant tumor arising from epithelium(carcinoma)

21. Clinical Manifestations of Bladder CA
1- Hematuria (80-90%) – Generally painless and may be gross or microscopic hematuria.
(it must be differentiated from other causes of hematuria as cystitis,prostatic leison)
2-Pain : often reflects tumor location
Lower abdominal pain – Bladder mass
Rectal discomfort & perineal pain – Invasion of prostate or pelvis.
Flank pain - Obstruction of ureters
3- Other urinary Symptoms:
Frequency, urgency, nocturia due to irritation of the mucosa or due to decrease bladder capacity.
The bladder is a source of gross hematuria (40%), but benign cystitis (22%) is a more common cause than bladder CA (15%). Microscopic hematuria is more commonly of prostate origin (25%); only 2% of bladder CAs produce microscopic hematuria.

22. investigations for Bladder Cancer
Investigations are recommended forPatients with hematuria, especially if > 40 years
Urinary Cytology to detect any desquamated malignant cells.
Cystoscopy, regardless of cytology results (main stay of dx)
Transurethral resection of all visible tumors to determine histology & depth of invasion
Biopsies of erythematous areas to assess for carcinoma in situ (CIS)i.e malignant cells still present in its place and not invade basement membrane.

23. investigations for Bladder Cancer
Imaging
cystoscopy
Ultrasonography
CT, or MRI - Can help determine extent of tumor spread (eg, into perivsesical fat, prostate or vagina, LNs)
CT chest / abdomen, MRI, radionuclide imaging of skeleton to assess for distant mets
Selective retrograde catheterization of the ureters up to the renal pelves to assess for upper tract dz.
The mainstay of dx & staging of bladder CA is cystoscopic eval, incl exam under anesthesia to determine if there is a palpable mass and, if so, whether it is mobile. A non mobile tumor mass indicates dz extending beyond the wall of the bladder & invading into regional organs (eg, prostate, vagina, or muscles along the pelvic sidewall); these tumors are unlikely to be surgically resectable. The bladder is visually inspected to detail the size, number, location, and growth pattern (papillary or flat) of all lesions.
U/S, CT, and/or MRI may help to determine whether a tumor extends to perivesical fat (T3) and to document nodal spread. Distant metastases are assessed by CT of the chest and abdomen, MRI, or radionuclide imaging of the skeleton.

24. Grading of transitional cell carcinoma ( i
Grading of transitional cell carcinoma ( i.e evaluating degree of similarity of the malignant cells to its normal counterpart)
1- low grade : if tumor cells are less pleomorphic,slightly similar to the cell of origin ,few mitosis, so have better prognosis.
2- high grade : worse prognosis because it have aggressive behavior, more infiltrative
As the cells highly pleomorphic, have more mitosis.

25. TNM staging for bladder carcinoma
T is tumor
N express lymph node affection by the tumor so :
N0 no affection to lymph nodes.
N+ the lymph nodes are infiltrated by the tumor
M express distant metastasis so :
M no distant metastasis
M+ there is distant metastasis.

26. Pathologic evaluation of bladder carcinoma tumor (PT)
In PT 0, abnormal cells are found in tissue lining the inside of the bladder. Stage 0 is divided into stage 0a and stage 0is, depending on the type of the tumor:
- PT 0a is also called papillary carcinoma, which may look like tiny mushrooms growing from the lining of the bladder.
- PT 0is is also called carcinoma in situ, which is a flat tumor on the tissue lining the inside of the bladder.
In PT I, cancer has formed and spread to the layer of tissue under the inner lining epithelium of the bladder .
In PT II, cancer has spread to either the inner half or outer half of the muscle wall of the bladder.

27. Staging of bladder carcinoma
In PT III, cancer has spread from the bladder to the fatty layer of tissue surrounding it and may have spread to the reproductive organs (prostate, seminal vesicles, uterus, or vagina).
In PT IV, cancer has spread from the bladder to the wall of the abdomen or pelvis. Cancer may have spread to one or more lymph nodes or to other parts of the body.

28. Bladder cancer: Stage and Prognosis
TNM stagging
Stage 0 Ta/Tis NoMo
Stage I T1 NoMo
Stage II T2a-b NoMo
Stage III T3a-4a NoMo
Stage IV T4b NoMo
any T N+Mo
any T M+

32. Complications of urinary bladder carcinoma
1- bleeding
2-Obstruction specially if the tumor grow near the urethral opening of the bladder lead to Bilateral Obstructive Uropathy in the form of hydroureter,hydronephrosis
4- Kidney Stones secondary to the obstruction and infection.
5- enterovesicular fistula is an abnormal channel that connects the interior of the urinary bladder with another structure within the abdomen. This can be found in cases of squamous cell carcinoma. This condition can present as gas or air in the urine. Repeated urinary tract infections may possibly occur if the urinary bladder becomes connected with the intestine

33. 6- spread of the malignant tumor either by :
a- direct spread to surrounding structures
b- hematogenous spread to distant organs.
c- lymphatic spread.

34. Treatment & Prognosis of Superficial Bladder Carcinoma
Requires at least complete endoscopic resection +/- intravesical therapy using Bacillus Calmette-Guérin (BCG) vaccine which act through stimulation of the immune system in such a way that the immune system begins to target and destroy any remaining cancer cells.
Superficial Disease
Inc’d risk for extravesical recurrences

35. Treatment of Muscle-Invasive Bladder Carcinoma
Generally radical cystectomy & pelvic lymphadenectomy
Removal of bladder & pelvic LNs with creation of a conduit or reservoir for urinary flow.
+ Removal of prostate, seminal vesicles, & proximal urethra in males. Generally  impotence.
+ Removal of urethra, uterus, fallopian tubes, ovaries, anterior vaginal wall, & surrounding fascia in females.
The probability of recurrence following surgery is predicted on the basis of pathologic stage, presence or absence of lymphatic or vascular invasion, and nodal spread.

36. Treatment of Muscle-Invasive Bladder Carcinoma
Concomitant Chemotherapy & Radiation
For those with a solitary early-stage lesion and no hydronephrosis
Generally use Cisplatin