MADE BY SMITH AND TANAGHO'S

1. URINARY BLADDER
TUMORS
MADE BY: IN

2. ANATOMY
O Bladder is a hollow muscular organ that
serves as the reservoir of urine.
O Adult bladder capacity =400-600 ml
O It plays two imp. roles :
temporary storage of urine
assists in expulsion of urine
O When empty, bladder lies behind the
pubic symphysis and is a pelvic organ and
when full its rises above the symphysis
and can be palpated and percussed.

4. I
O Bladder has a apex anteriorly, fundus or base
posteroinferioly and body located between
fundus and apex.
O Neck formed by convergence of fundus and two
inferolateral surfaces and continues with urethra
O urine enters bladder through right and left
ureters
internally these orifices are marked by the
trigone
O Blood supply is by
branches of internal iliac(the superior and
inferior vesical arteries) in males
vaginal arteries in females obviously

5. v
O Venous drainage is achieved by vesical
venous plexus which drains into internal iliac
veins.
O Lymphatic drainage:
 superolateral aspect drains into external
iliac lymph nodes
 neck and fundus drain into internal iliac,
sacral and common iliac nodes

6. histology
O The normal urothelium is composed of three to seven layers
of transitional layers of transitional cell epithelium resting on
basement membrane.
O The epithelial cells vary in appearance; the basal cells
resting on basement membrane and luminal cells are larger
umbrella like cells that are bound together by tight junctions.
O Beyond basement membrane is loose connective tissue,
lamina propria with smooth muscle fibers.
O Then comes muscularis propria which consists of three
layers: inner longitudinal ,middle circular and outer
longitudinal
O Serosa is thin connective tissue layer which blood vessels
O Adventitia which serves as bladder outer layer in areas
where there is no serosa

9. Bladdercarcinomaincidence
O Bladder cancer is the 2nd most common cancer
of genitourinary tract.
O The incidence is higher in whites than in african-
american.
O The average age at diagnosis is 65yrs.
O By that age, 75% of bladder cancers are
localized to bladder; 25% will have spread to
regional lymph nodes or distant sites.
O It accounts 7% of new cases in men and 2% of
new cases in women

10. Risk factors
O Cigarette smoking accounts for 65% of cases in
men and 20-30% in women.
O Smokers have two to three fold greater risk than
non-smokers and this is due secretion of alpha
and beta naphthylamine in the urine.
O Occupational exposure accounts for 15-35%
cases in men and 1-6% in women. Workers in
dye, chemical, rubber, petroleum, leather and
printing industries have higher risk.
O Patients who have received cyclophaosamide for
malignant diseases are at high risk.

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O Physical trauma to urothelium induced by
infection , instrumentation and calculi inc. risk of
malignancy.
O Arsenic in drinking water has been implicated as
a causative agent for bladder cancer.
O Ingestion of artificial sweeteners has been
proposed to be a risk factor but several studies
has denied that.

16. pathogenesis
O The exact genetic events leading to development
of bladder cancer are unknown but are likely to
be multiple and involve activation of oncogenes.
O Loss of genetic material on chromosome 9
appears in pt. with low stage, low grade and high
grade, high stage disease.
O 11p which contains c-Ha-ras-proto oncogene
detected in 40% of bladder cancers.
O Inc. expression of c-Ha-ras protein, p21 has been
detected in dysplastic and high grade tumours.

17. v
O Deletion of 17p detected in over 60% in all
invasive bladder cancers.
O TP53 alterations represent most common
finding in human cancers, deletion of this
chromosome in imp. Finding in CIS and
muscle invasive tumours
O Fibroblast growth factor 3(FGFr3) is found in
>60% papilloma's and low grade tumours.
O RAS mutations are found in both low grade ,
high grade and muscle invasive tumours.
O Muscle invasive bladder cancers have high
mutation rate. Common mutated genes are
TP53, ERCC2, FGFr3,ERBB2,KDM6A etc.

18. m
O ERCC2 are more commonly found in
smokers.
O Bladder cancers that arise from luminal
cells tend to be papillary and have better
prognosis.
O Cancers that arise from basal cells tend to
have worst prognosis but appear to be
more responsive to chemotherapy.

19. histopathology
OOf all bladder cancers, 95% are
transitional cell carcinomas and
about 5% of adenocarcinoma,
squamous cell carcinoma,
neuroendocrine tumours and other
histological subtypes.

20. papilloma/PUNLMP
O WHO recognizes papilloma as papillary
tumour with a fine fibro vascular stalk
supporting epithelial layer of transitional
cells with normal thickness and cytology.
O Also termed as papillary urothelial
neoplasms of low malignant potential
which are rare benign conditions which
don’t require aggressive treatment.

21. BENIGN PAPILLOMA

24. Transitional cell carcinomas
O 90% of all cancers
O Appear as papillary exophytic
lesions(superficial) or sessile or
ulcerated(invasive)lesions.
O These carcinomas can be formed purely
of urothelial cells or have a minor
histological variant. These variants could
be nested, microcystic, signet ring,
squamous, micro papillary, lipid rich, clear
cells or giant cells; be of mullerian type.

27. Non-urothelial cell carcinomas
1. Adenocarcinomas:
<2% cases are mucus secreting have
glandular colloid or signet ring pattern. They
arise on the floor of bladder,
adenocarcinomas arising from the urachus
occur at dome.
Both cancers are localized at the time of
diagnosis but muscle invasion in usually
present.

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2. Squamous cell carcinoma:
5-10% cases. Invasive bladder cancer
associated with h/o chronic inf., chronic catheter
use, vesical calculi and also with Schistosoma
haematobium bcoz it accounts for 60% of all
bladder cancers in Egypt, parts of Africa and
middle east.
Often nodular and invasive at the time of
diagnosis and appear as poorly differentiated
neoplasm composed of polygonal cells and
intercellular bridges.

31. Squamous cell carcinoma of the urinary
bladder showing well-formed keratin pearls
(a) and corresponding immunoreactivity
with p16 (b).

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3.Undifferentiated carcinomas:
rare<2%. No epithelial element.
Neuroendocrine features with small ones
being aggressive and present with
metastasis.
O Carcinoma in situ:
flat anaplastic epithelium which lacks
normal cytology and contain hyperchromatic
nuclei with prominent nucleoli.

34. Rare epithelial and non epithelial cancers
O Rare epithelial cancers:
• Adenoma
• Carcinoid tumour
• Carcinoscarcoma
• Melanomas
O Epithelial cancers:
• Pheochromocytoma
• Lymphoma
• choriosarcoma

35. Most common tumour metastatic to the bladder
according to incidence
O Melanoma
O Lymphoma
O Stomach
O Breast
O Kidney
O Lung
O liver

36. symptoms
O Haematuria is a presenting symptom in
85-90%. It maybe gross or microscopic,
intermittent or constant.
O Accompanied by symptoms of vesical
irritability :frequency, urgency, dysuria.
O Advance disease include bone pain from
bone metastases or flank pain from
retroperitoneal metastases
O Extensive tumours can present with pain
radiating to buttocks and thighs.

38. SIGNS
O Pt. with large volumes or invasive tumours may
have wall thickening or palpable mass –detected
on bimanual examination under anaesthesia.
O If bladder not mobile may suggest fixation to
adjacent structures by direct invasion
O Hepatomegaly and supraclavicular
lymphadenopathy(signs of metastasis disease)
O Lymphedema from occlusive lymphadenopathy
O Painful nodules with ulceration on skin if
metastases.

39. investigations
O CBC : anaemia may be present due to blood
loss or replacement of bone marrow by
metastatic disease
O Urinalysis:
 Haematuria most common
 Pyuria due to concomitant urinary tract
infection.
 Azotaemia maybe noted in pts with ureteral
occlusion.
O Urinary cytology: exfoliated cells from both
normal and neoplastic urothelium can be
identified in voided urine. High grade and CIS
have +ve cytology.

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O Other markers: bladder tumour antigen BTA,
NMP22 assay, NMP22 bladder chektest, the
immunocyst test, Cxbladder test. Cx bladder test
detects specific mRNA in the urine to predict the
likelihood of cancer
O CT/MRI: To detect the extend of cancer invasion
and to detect enlarged nodes.
CT SCAN is more accurate for evaluation of
entire abdominal cavity, renal parenchyma and
ureters in pt.
With haematuria.
MRI using 3T scanners appears to be particularly
helpful in detecting lymphadenopathy but small
pelvic lymph nodes are always missed that’s why
PET CT can be used to detect microscopic nodal

43. i
OChest x-ray and bone scan: to
complete staging bcoz some
invasive cancers metastasize to
lungs and bones.
OCystoscopy
Obiopsy

45. Cystourethroscopy and tumour resection
O The diagnosis and initial staging of bladder cancer is
made by cystoscopy and transurethral resection
O Cystoscopy can be flexible or rigid
O Flexible cystoscopy is associated with less discomfort
and only requires local anaesthesia
O Non muscle invasive, low grade tumours appear as
single or multiple papillary lesions
O Higher grade lesions are larger and sessile
O CIS appear as flat areas of erythema and mucosal
irregularity.
O Use of fluorescent cystoscopy with blue light can
detect lesions by as much as 20%

47. o
O If tumour is visualized or suspected then
patient is scheduled for examination under
anaesthesia and TUR or biopsy.
O Objectives are:
 Assessment of invasion of bladder
wall(staging)
 Complete excision of all visible lesions if
possible

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patient in lithotomy
bimanual examination
cystoscopy repeated with one or more
lenses(30,70)
RETROSCOPE
Electrocautery and removal of visible lesions
Suspicious areas biopsied with cup biopsy forceps
Areas cauterized with electrode

51. treatment
A. Intravesical chemotherapy: immuno or
chemotherapeutic agents can be
instilled into the bladder via catheter,
thereby avoiding the morbidity of
systemic administration in most cases
O Prophylactically to reduceTumor cell
transplantation
OAlso therapeutically to reduce risk of
reoccurrence and progression for low risk
tumours

53. i
O Mitomycin C: antitumor, antibiotic, alkylating agent that
inhibits DNA synthesis. Its given 40mg in 40ml of sterile
water or saline given once a week for 6 wks.
S.E: in 10-43% frequency, urgency, dysuria, rash on
palms and genital
O Gemcitabine: used in pts not responding to BCG.
These agents are well tolerated and is a cost effective
alternative to mitomycin C
O BCG:MYOBACTERIUM BOVIS, very effective
therapeutically and prophylactically. Most efficacious
agent in treatment of CIS. Complete responses in 36-
71% pts. The most common induction regimen is
weekly for 6 wks and 6 wks with no BCG.
S.E: mucosal ulceration and granuloma formation
Should be discontinued in pts. With BCG sepsis(high
fever, chills, confusion, hypotension and resp. failure,
jaundice)

54. B. surgery
O TURB: initial form of treatment for all bladder
cancers. Pts with single, low grade non invasive
tumours treated with TURB alone. Superficial
disease but high risk features should be treated
with TUR followed by selective dose of
intravesical therapy. Careful follow-up of pts with
superficial disease is mandatory bcoz disease
with recur in 30-80% of pts. Disease status after 3
months is very imp for the risk for recurrence after
initial resection.
pts. With low risk tumours who are free of 3 month
recurrence repeat cystoscopy after 1 yr and in pts
with high risk tumours after 3 months its necessary.

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O PARTIAL CYSTECTOMY: for solitary, infiltrating
tumours(T1-T3) localized along the posterior lateral
wall and dome of the bladder. Patients with CIS and
those with lymph node metastasis don’t respond to this
treatment.
O RADICAL CYSTECTOMY: removal of anterior pelvic
organs: in men, bladder with surrounding fat and
peritoneal attachment, prostrate, and seminal vesicles.
In women, bladder with its surrounding fat and
peritoneal attachment, cervix, uterus, ant. Vaginal vault,
urethra and ovaries.
Gold standard for muscle invasive cancers.
recurrence after surgery usually occurs after 3 yrs. The
risk of urethral tumour occurrence in men is 6.1-10.6%.
Urethrectomy was once performed in all pts undergoing
cystectomy but now bladder replacement is acceptable
procedure.

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C. RADIOTHERAPY: external beam irradiation
(5000-7000cGy) over a period of 5-8wks. Alternative
to radical cystectomy in well selected pts with
invasive bladder carcinoma. Recurrence is common,
occurring in 33-68%. 5 yrs. survival rate for T2-T3
stage.
D. IMMUNOTHERAPY: although initial choice for
advance bladder cancer is chemotherapy but such
cancers have shown response to immunotherapy
specifically programmed death ligand 1(PD-L1)
atezolizumab. This class helps rejuvenate the
immune response to tumour by eliminating
checkpoints that serve to suppress tumour. Cancers
with high mutational load respond best

59. chemotherapy
O Almost 15% pts presenting with bladder cancer are
found to have regional or distant metastases.
O 30-40% develop distant metastasis even after
radical cystectomy or radiotherapy.
O Combination of chemotherapeutic agents cisplatin,
active agent when used alone and produces
response in 30%
O Methotrexate, doxorubicin, vinblastine,
cyclophosphamide, gemcitabine, 5-fluorouracil.
O Regimen of methotrexate, vinblastine, doxorubicin
and cisplatin(MVAC) commonly used in pts with
advanced bladder caners.

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carcinoma in situ
BCG( weekly for 6 wks) plus maintain for
3yrs
cystoscopy at 3 and 6 months
Persistent carcinoma in situ at 6 months
O YES= radical cystectomy or clinical trial
or salvage intravesical therapy
O NO= continue BCG, continue surveillance
cystoscopy every 3 months for 2 yrs. and
then every 6 months for 2 yrs. and then
annually

61. Treatment selection
O Management of low grade NMIBC characterized by primary,
single, papillary Ta under 3cm can be treated by TUR alone
and instillation intravesical chemotherapy.
O Pts with intermediate NMIBC can be treated with TUR with
instillation of intervesical chemotherapy with addition chemo
or immunotherapy with BCG.
O High risk NMIBC treated with intravesical immunotherapy
after complete and careful TUR.
O Some patients with larger tumours, variant histology and
angiolymphatic invasion maybe candidates for radical
cystectomy.
O Pts with(T2-T3) are candidates for partial or radical
cystectomy and radiation and systemic chemotherapy
O Pts with T4b treated with systemic chemotherapy
O Pts with distant metastasis should be treated with systemic
chemotherapy followed by selective use of irradiation or
surgery
O Pt with recurrence after use of BCG treated with cystectomy

62. thankyou