non invasive bladder growth at department of urology,sindh pakistan

2.  It is musculomembranous sac which acts as reservoir for urine & its size, position
& relations vary according to amount of fluid it contains
 It has maximum capacity of approx: 500ml.
 Empty bladder is pyramidal in shape & when it fills becomes ovoid in shape having
apex base superior two inferolateral surfaces & neck.
 Apex of bladder points ant: & is connected to umbilicus by median umblical
ligament (remains of urechus)
 Base of bladder faces post: & is triangular in shape
Anatomy of Bladder

3. Wall of bladder consist of four layers
SERIOUS COAT
 It is partial one & derived from peritoneum. It invests superior surface & upper
part of lateral surface
MUSCULAR COAT
 Detrusor muscle is muscle of urinary bladder wall
 Consists of three layers of smooth muscular fibers
 External,middle & internal layer having longitudinal & circular arrangements.
SUB MUCOSAL COAT
 It is thin layer of areolar tissue that loosely connect muscular layer with mucous
layer
MUCOSAL COAT
 It is inner most layer of urinary bladder & contains transitional epithelial tissues
 loose texture allows mucous coat to be thrown into folds or rugæ when bladder is
empty.

5.  Main arteries supplying bladder are branches of int: iliac artery
 Sup: vesicle artery supply anterosuperior part of bladder.
 Inferior vesicle arteries (in males) or vaginal arteries (in females)
supply base of bladder.
 Obturator & inferior gluteal arteries also supply small branches to
bladder.
 Veins from venous plexus on inferolateral surface & drain back to
internal iliac vein
Blood supply

6. Lymphatic drainage
 Lymph vessels from superior part of bladder pass to external iliac
nodes.
 Those from inferior part of bladder pass to internal iliac nodes.
 Some lymph vessels from neck region of bladder drain into
sacral or common iliac nodes.
Innervation of bladder
 Receives Parasympathetic innervation from S2-4 segments of spinal
cord,They are motor to detrusor & inhibitory to internal sphincter.
 Receives Sympathetic innervation from T11-12, L1-2 segments of spinal
cord,Cause constriction in internal sphincter & inhibit detrusor muscle.

7. • It is uncontrolled abnormal growth & multiplication of cells in
bladder
• It is seventh most commonly diagnosed cancer in male population
and eleventh when both genders are considered
• The worldwide age-standardised incidence rate is 9.0 for men and
2.2 for women
• Approximately 75% of patients with BC present with a disease
confined to the mucosa (stage Ta, CIS) or submucosa (stage T1)

8. • Tobacco smoking is the most important risk, accounting for approx 50%
of cases .
• Occupational exposure to aromatic amines, polycyclic aromatic
hydrocarbons and chlorinated hydrocarbons is the second most
important risk factor accounting for about 10% of all cases.
• Mainly in industrial plants, which process paint, dye, metal and
petroleum products
• Family history have little impact and, to date, no overt significance of any
genetic variation for BC has been shown
• Chronic infection: Schistosomiasis, a chronic endemic cystitis based on
recurrent infection with a parasitic trematode, is also a cause of BC
• Chlorination of drinking water and exposure to arsenic in drinking water
are potentially carcinogenic
• Drugs: weak association is also with l cyclophosphamide and pioglitazone
• Radiation: Exposure to ionizing radiation is connected with increased risk

9. Transitional Cell Carcinoma
 More than 90% of bladder cancers are TCCs
 It demonstrate variety of patterns of tumor growth, including flat,
papillary, sessile, infiltrating, nodular, mixed
 Most common are papillary exophytic lesions
 Nonpapillary (sessile) or ulcerated tumors are less common.
However, they are more invasive & have worse outcome.
NON TRANSITIONAL CELL CARCINOMA
• Adenocarcinoma.Squamous cell carcinoma.Small cell
carcinoma.Carcinosarcoma.Metastatic carcinoma

10. • Papillary tumours confined to mucosa and
invading lamina propria are classified as stage Ta
and T1
• Flat, high- grade tumours that are confined to
mucosa are classified as CIS (Tis)
• These tumours can be treated by transurethral
resection of the bladder (TURB), eventually in
combination with intravesical instillations and are
therefore grouped under heading of NMIBC for
therapeutic purposes.

11. Histological grading of non-muscle-
invasive bladder urothelial carcinomas

13. • It is a flat, high-grade, non-invasive urothelial carcinoma.
• It is presence of cancerous-appearing cells, proliferating in
abnormally high number, but are confined to transitional
epithelium
• It is always high grade & appear as velvety patch of
erythematous mucosa & often endoscopically invisible
• It can be missed or misinterpreted as an inflammatory
lesion during cystoscopy if not biopsied.
• Carcinoma in situ is often multifocal and can occur in the
bladder, but also in the upper urinary tract (UUT), prostatic
ducts, and prostatic urethra
• Without any treatment, approximately 54% of patients
with CIS progress to muscle-invasive disease

14. Classification of CIS according to
clinical type
Primary:
Isolated CIS with no previous or concurrent
papillary tumours and no previous CIS
Secondary:
 CIS detected during follow-up of pats with
previous tumour that was not CIS
Concurrent:
CIS in presence of any other urothelial tumour in
bladder
Recurrent:
Repeat occurrence of isolated CIS after initial
successful response to intravesical treatment.

15. • It is diagnosed by combination of cystoscopy, urine cytology, and histological
evaluation of multiple bladder biopsies.
• Biopsies are taken from suspect areas esp: In pats with i.e positive urine cytology
and no papillary tumour
• The risk of prostatic urethra or duct involvement is higher if the tumour is located
at trigone or bladder neck, in the presence of bladder CIS and multiple tumours
Based on this observation, a biopsy from the prostatic urethra is necessary in some
cases
• Multiple biopsies from normal looking mucosa including prostatic urethra (random
biopsies) are recommended.
• If equipment is available, photodynamic diagnosis (PDD) is useful tool to target
biopsy in these pats.

17. PATIENT HISTORY
• A comprehensive patient history is mandatory.
SIGNS AND SYMPTOMS
• Haematuria is the most common finding in NMIBC.
• Visible haematuria is found to be associated with higher stage disease
compared to nonvisible haematuria at first presentation
• Carcinoma in situ might be suspected in pats with lower urinary tract
symptoms, especially irritative voiding.
PHYSICAL EXAMINATION
• Physical examination does not reveal NMIBC.
• Ultrasound may be performed as an adjunct to physical examination as it
has moderately high sensitivity to a wide range of abnormalities but
cannot rule out all potential causes of haematuria

18. Computed tomography urography
• Computed tomography (CT) urography is used to detect
papillary tumours in the urinary tract
• The necessity to perform a baseline CT urography or IVU
once a bladder tumour has been detected is questionable
due to the low incidence of significant findings obtained
Ultrasound (US)
• Transabdominal US permits characterisation of renal
masses, detection of hydronephrosis, and visualisation of
intraluminal masses in bladder
• Ultrasound is therefore a useful tool for detection of
obstruction in patients with haematuria.
• However, it cannot exclude the presence of UTUC and
cannot replace CT urography in bladder cancer detection.
• The diagnosis of CIS cannot be made with imaging methods
(CT urography, IVU or US)

19. Urinary cytology
• The examination of voided urine or bladder-washing specimens for
exfoliated cancer cells has high sensitivity in G3 and high-grade
tumours (84%), but low sensitivity in G1 and low-grade tumours
(16%)
• Positive voided urinary cytology can indicate urothelial tumour
anywhere in the urinary tract; negative cytology, however, does
not exclude the presence of a tumour.
• Evaluation can be hampered by low cellular yield, urinary tract
infections, stones, or intravesical instillations

20. Cystoscopy
• The diagnosis of papillary BC ultimately depends on cystoscopic
examination of the bladder and histological evaluation of sampled
tissue by either cold-cup biopsy or resection.
• Cystoscopy is initially performed as outpatient procedure.
• A flexible instrument with topical intra-urethral anaesthetic lubricant
instillation results in better compliance compared to a rigid
instrument
Urinary molecular marker tests
• None of these markers have been accepted for diagnosis or follow-up
in routine practice or clinical guidelines.
• There is List of established urine tests that are FDA approved

22. • As standard procedure, cystoscopy and TURB are
performed using white light.
• However, use of white light can lead to missing
lesions that are present but not visible, which is
why new technologies are being developed.
1. PHOTODYNAMIC DIAGNOSIS (FLUORESCENCE CYSTOSCOPY)
2. Narrow band imaging (NBI)

23. • PDD is performed using violet
light after intravesical
instillation of 5
aminolaevulinic acid (ALA) or
hexaminolaevulinic acid (HAL).
• Photoactive porphyrins
accumulate preferentially in
neoplastic tissue. Under blue
light they emit red
fluorescence, which can help
in diagnosis of indiscernible
malignant lesions.
• When this technology is used,
both small papillary tumors
and almost one third more
cases of CIS overlooked on
cystoscopy are identified

24. • Is optical image enhancement technology intended to
improve visibility of blood vessels inherent to
neoplastic processes.
• NBI light is composed of two specific wavelengths
that are absorbed by hemoglobin; 415-nm light
penetrates only the superficial mucosal layers,
whereas 540-nm light penetrates more deeply.
• Combination allows improved visualization of tumors.
• Clinical impact of this remains under investigation,
and no studies have been performed to date
regarding recurrence or progression

26. • Perform resection in one piece for small papillary tumours (< 1 cm),
including part from underlying bladder wall.
• Perform resection in fractions (including muscle tissue) for tumours >
1 cm in diameter.
• Biopsies should be taken from abnormal-looking urothelium.
• Biopsies from normal-looking mucosa (trigone, bladder dome, and
right, left, anterior and posterior bladder walls) are recommended
only when cytology is positive or when exophytic tumour has non-
papillary appearance.

27. TURB should be performed systematically in
individual steps:
• Bimanual palpation under anaesthesia
• Insertion of resectoscope, under visual control with
inspection of whole urethra,inspection of whole
urothelial lining of bladder;
• Resection of tumour
• Bimanual palpation after resection
• Biopsy from prostatic urethra (if indicated)
• Cold-cup bladder biopsies (if indicated)
• Protocol formulation
• Formulation of order form for pathological
evaluation.

28. SECOND TURB IS RECOMMENDED IN FOLLOWING SITUATIONS:
• After incomplete initial TURB
• if there is no muscle in specimen after initial resection
• with exception of Ta G1 tumours and primary CIS, in all T1
tumours
• in all G3 tumours, except primary CIS.
• When done, second TURB should be performed within 2-6
weeks after initial resection.
• Pathological report should specify tumour location, tumour
grade, depth of tumour invasion, presence of CIS, and whether
detrusor muscle is present in specimen

29. MONOPOLAR AND BIPOLAR RESECTION
• Compared to monopolar resection, bipolar resection has
been introduced to reduce the risk of complications (e.g.,
bladder perforation due to obturator nerve stimulation) and
to produce better specimens for the pathologist. Currently,
the results remain controversial
OFFICE-BASED FULGURATION AND LASER VAPORISATION
• In patients with a history of small, TaLG/G1 tumours,
fulguration of small papillary recurrences on an outpatient
basis can reduce the therapeutic burden and is a treatment
option
• Potassium titanyl-phosphate (KTP) laser vaporisation is
associated with a low risk of complications. Its oncologic
outcomes need to be confirmed in a larger patient population

30. • Since there is considerable risk for recurrence or progression of tumours
after TURB, adjuvant intravesical therapy is recommended for all stages
(Ta, T1, and CIS).
• Immediate postoperative instillation of chemotherapy within 6 hours after
TURB is recommended in tumours presumed to be at low or intermediate
risk
• Choice of drug (mitomycin C, epirubicin, or doxorubicine) is optional
• Intravesical chemotherapy reduces risk of recurrence but not progression
• Intravesical immunotherapy with Bacillus Calmette-Guérin (BCG)
(induction and maintenance) is superior to intravesical chemotherapy in
reducing recurrences and in preventing or delaying progression to muscle-
invasive bladder cancer but it is more toxic.

31. 1:Mitomycin C
• Used to prevent tumor implantation
• Antibiotic derivative that inhibits DNA synthesis via alkylation,
• “larger” molecule,systemic absorption rare unless perforation
• Recurrence rate dec by 30-50% and inc recurrence-free interval
• 20-40mg/20-40mL of sterile water
• Single dose within 6 hours and Intravesical “face-time” of 1 - 2hour
• optimal schedule of further intravesical chemotherapy instillation and its
duration is not defined and should not exceed 1 year. Destroys residual
microscopic tumor at TURBT site
Side effects
• Skin rash- palmar desquamation.Irritative symptoms and chemical cystitis
(10%),Rarely, contracted bladder
Contraindications:
• Perforation,gross hematuria

32. 2:Doxorubicin
•Inhibits topoisomerase II and thus inhibits protein synthesis
Shown to prevent recurrence but not progression
3:Valrubicin
•Approved for treatment of BCG refractory CIS who refuse or are
unfit for radical cystectomy
4:Epirubicin
•Dec recurrence when compared to TUR alone
•Not FDA approved in US
5:Thiotepa:
• Only agent approved for treatment of papillary urothelial
bladder cancer original and cheapest intravesical agent,
• Alkylating agent that is >50% absorbed causses
Myelosuppression

33. 1:BCG
• Bacillus Calmette-Guerin,Live, attenuated Mycobacterium bovis,Used
initially as Tb vaccine
• Act by creating massive local immune response all reflecting Th1
process driven by Direct binding of fibronectin within bladder wall
Use in CIS
• CIS is often diffuse preventing complete tumor resection
• Induction and induction + maintenance
Use as prophylaxis for 6 weeks after TURBT
• Induction dec recurrence by up to 40% for T1 lesions compared to
TUR alone
• Induction + Maintenance can reduce progression by 20-30% in HG
tumors
• Maintenance is thought to provide long-term immunostimulation

34. BCG Scheduling
• Induction BCG instillations are given according to the empirical six-weekly
schedule
• For optimal efficacy, BCG must be given in a maintenance schedule
• Many different maintenance schedules have been used, ranging from a total of
ten instillations given in eighteen weeks to 27 over three years
• when BCG is given at full dose, three years’ maintenance (three-weekly
instillations 3, 6, 12, 18, 24, 30 and 36 months) reduces recurrence rate
B:Interferons:
 Are glycoproteins produced in response to antigenic stimuli.
 Interferons have multiple antitumor activities, including inhibition of
nucleotide synthesis; upregulation of tumor antigens, antiangiogenic
properties & stimulation of cytokines
 Interferon as solitary agent is more expensive & less effective than BCG or
intravesical chemotherapy in eradicating residual disease, preventing
recurrence of papillary disease & treating CIS

40. Reasons to consider immediate RC for selected patients with
NMIBC:
• The staging accuracy for T1 tumours by TURB is low with 27-51%
of patients being upstaged to muscle-invasive tumour at RC
• Patients who experience disease progression to muscle-invasive
stage, have a worse prognosis than those who present with
‘primary’ muscle-invasive disease
• A delay in RC may lead to decreased disease-specific survival
• In patients in whom RC is performed before progression to
MIBC, the five-year disease-free survival rate exceeds 80%
• The potential benefit of RC must be weighed against its risks,
morbidity, and impact on quality of life. It is reasonable to
propose immediate RC in those patients with NMIBC who are at
highest risk of disease progression

41. Recommendations for follow-up Ta, T1 tumours and CIS
• Pats with low-risk tumours should undergo cystoscopy at 3
months. If negative, subsequent cystoscopy is advised 9
months later, then yearly for 5 years.
• Pat with high-risk tumours should undergo cystoscopy and
urinary cytology at 3 months. If negative, subsequent
cystoscopy and cytology should be repeated every 3
months for period of 2 years, and every 6 months
thereafter until 5 years, and then yearly.
• Pats with intermediate-risk Ta tumours should have in-
between follow-up scheme using cystoscopy and cytology,
which is adapted according to personal and subjective
factors.

42. • Regular (yearly) upper tract imaging (CT-IVU or
IVU) is recommended for high-risk tumours.
• Endoscopy under anaesthesia and bladder
biopsies should be performed when office
cystoscopy shows suspicious findings or if urinary
cytology is positive.
• During follow-up in pats with positive cytology
and no visible tumour in bladder, R-biopsies or
biopsies with PDD (if equipment is available) and
investigation of extravesical locations (CT
urography, prostatic urethra biopsy) are
recommended.