Kower urinary tract disorders

1. LOWER URINARY TRACT
DISORDERS
Presenter: KEMBOI AARON – MED VI
Facilitator : Dr. MUGALO
Friday, April 30, 2021

2. OUTLINE
1. Congenital disorders of lower urinary tract- bladder and urethra
2. Acquired disorders of lower urinary tract-
a) Urinary tract infections- cystitis, urethritis
b) Urological obstructions- urethral strictures
c) Neoplasms- benign and malignant
(bladder,urethra,prostate,testis,penile tumors)
d) Inflammations- BPH, Testicular torsion

3. CONGENITAL ANOMALIES OF THE BLADDER
Bladder exstrophy
• Exstrophy of the bladder is a rare congenital anomaly with complete ventral defect of the urogenital sinus and the overlying skeletal
system.
• Incidence of 3.3 per 100,000 births. Male–female ratio 4:1
• In the male, the penis is broad and short, and bilateral inguinal herniae may be present. In epispadias alone, the pubes are united and
external genitalia are almost normal, although in the female the clitoris is bifid
Treatment
• The bladder is closed in the first year of life, usually following osteotomy of both iliac bones just lateral to the sacroiliac joints.
• Later, reconstruction of the bladder neck and sphincters is required. In some patients the reconstructed bladder remains small and
requires augmentation
• Long-term complications include:
(1) stricture at the site of anastomosis with bilateral hydronephrosis and infection;
(2) hyperchloraemic acidosis; and
(3) an increased (20-fold) risk of tumour formation (adenoma and adenocarcinoma) at the site of a ureterocolic anastomosis.

4. CONGENITAL ANOMALIES OF THE URETHRA
Urethral stricture
• Congenital urethral stricture is rare.
• The fossa navicularis and membranous urethra are the two most common sites. Severe strictures may
cause bladder damage and hydronephrosis, with symptoms of obstruction (urinary frequency and
urgency) or urinary infection. Usually, symptoms are delayed until adolescence, when it may be
indistinguishable from a stricture due to unrecognised urethral injury in childhood.
• Excretory urography and excretory voiding urethrography often define the lesion and the extent of
obstruction. Retrograde urethrography may also be helpful. Cystoscopy and urethroscopy should be
performed in all patients in whom urethral stricture is suspected.
• A single treatment by optical urethrotomy or dilatation is usually effective.

5. Posterior urethral valves
• The most common obstructive urethral lesions in infants and newborns,
occur only in males. Incidence of 1 in 5000–8000
• They are usually just distal to the verumontanum but they may be within the
prostatic urethra. They are flap valves and so, although urine does not flow
normally, a urethral catheter can be passed without difficulty.
• They may cause varying degrees of obstruction when the child attempts to
void and may present with mild, moderate, or severe symptoms of
obstruction. They often have a poor, intermittent, dribbling urinary stream.
Urinary infection and sepsis occur frequently. Sometimes the valves are
incomplete and the patient is symptom free until adolescence or adulthood.
• Posterior urethral valves need to be detected and treated as early as possible
to avoid the development of renal failure.

6. PUV…
• Diagnosis may be made antenatally with ultrasound, which demonstrates bilateral
hydronephrosis above a distended bladder.
• Investigation- Voiding cystourethrogram- demonstrates dilatation of the urethra
above the valves. The bladder is hypertrophied and often shows diverticula.
Typically, there is vesicoureteric reflux into dilated upper tracts
• Renal function is usually impaired. ultrasound scanning assess the renal cortical
thickness, and renography to assess differential renal function.
Treatment
• Initial treatment is by catheterisation to relieve the obstruction and to allow the
effects of renal failure to improve.
• Definitive treatment is by transurethral resection of the valves. with continuing
lifelong supportive treatment of the dilated urinary tract, the recurrent urinary
infections and the uraemia.

7. Hypospadias
• The urethral meatus opens on the ventral side of the penis proximal to the tip of
the glans penis.
• occurs in around 1 in 200–300 male live births and is the most common congenital
abnormality of the urethra.
• Estrogens and progestins given during pregnancy are known to increase the
incidence. Although a familial pattern of hypospadias has been recognized, no
specific genetic traits have been established.
• There are several forms of hypospadias classified according to location:
glandular(opening on the proximal glans penis), coronal (opening at the coronal
sulcus), penile shaft, penoscrotal, and perineal. About 70% of all cases of
hypospadias are glandular or coronal.
• Hypospadias does not cause either obstruction or urinary tract infection.
• Surgery is indicated to improve sexual function, to correct problems with the
urinary stream and for cosmetic reasons.

8. 8
epispadias
• A very rare congenital condition in which the urethra opens on dorsal
surface of penis
• In penile epispadias, the opening on the dorsum is associated with
upward curvature of the penis. Epispadias usually coexists with
bladder exstrophy and other severe developmental defects.

9. Urinary tract infection
Definition
• UTI refers to infections, at any level of the urinary tract, including urethra
(urethritis), bladder (cystitis), renal pelvis (pyelitis), or renal parenchyma
(pyelonephritis).
• Upper (pyelonephritis) & Lower (Urethritis, cystitis, prostatitis)
 Uncomplicated: UTI without underlying renal/ neuro dse
 Complicated: UTI with underlying structural, medical or neuro dse
 Recurrent: >3 symptomatic UTIs in 12 months following clinical therapy
 Reinfection: Recurrent UTI caused by diff pathogen at any time
 Relapse: recurrent UTI caused by same species causing original UTI within
2wks after therapy

10. Epidemiology
• 150million cases per year
• 90% cystitis, 10% pyelonephritis
• 75% recurrent, 25% recurrent
• 2% complicated
• Almost half of all women will have at least 1
UTI in their lives, with risk increased after
menopause
• Urinary catheterization increases risk up to
10fold
Gender
• Infants and children: M>F
• Adolescent-menopause: F>M
• Older age: F=M
Women?
- shorter urethra
- Close proximity to perianal areas
- Sexual contact: pathogens colonize bladder
- Spermicidal change of normal flora
Men
Prostate infection, anatomical defects, lack of
circumcision, homosexuals

11. Risk factors
• Sexual intercourse
• Diabetes- neurogenic bladder
• Obstructive uropathy
• Disturbances in ureteral functioning
• Vesicoureteral reflux in children
• Uterine prolapse
• BPH
• Spinal injury
• Stones
• Catheterization and other procedures
• Renal transplant
Host protective factors in UTI
• Flushing mechanism of micturition
• Acid pH of urine(4.6-6) antibacterial
• Acid vaginal Ph(3.5-5.5) suppresses
colonization
• Urinary Tamm-Horsefall protein (secreted
by asecending loop of Henle) and blocks
E.coli
• Chemotactic factors interleukin 8

12. AETIOLOGY
• Bacterial infections are the most common cause of UTI, with E coli being the most
frequent pathogen, causing 75-90% of UTIs. Other bacterial sources of UTI include the
following:
 Klebsiella species
 Proteus species
 Enterococcus species
 Staphylococcus saprophyticus, especially among female adolescents and sexually active females
 Streptococcus group B, especially among neonates
 Pseudomonas aeruginosa
• Complicated UTI- E. coli, Staphylococcus aureas, Pseudomonas aeruginosa
• Fungi (Candida species) may also cause UTIs, especially after instrumentation of the
urinary tract. Other fungi species: aspergillus, c. neoformans, endemic mycoses
• Adenovirus is a rare cause of UTI and may cause hemorrhagic cystitis. Other viruses:
enterovirus, coxsackie, echovirus
• Protozoa- T. vaginalis, S. haematobium

13. Pathogenesis
• Majority of the infections are ascending infections.
• Typically, UTIs develop when uropathogens that have colonized the
periurethral area ascend to the bladder via the urethra. From the
bladder(cystitis), pathogens can spread up the urinary tract to the kidneys
(pyelonephritis) and possibly to the bloodstream (bacteremia)..
• Introduction of the bacteria is via various mechanisms;
• A back to front wiping motion may collect the bacteria from the anus to the
genitourinary system(mostly E.coli)
• Non sterile urinary catheters and other devices
• Its usually direct inoculation of the causative organisms
• Sexual intercourse
• Most common method via which UTIs secondary to staphylococcus saprophyticus are spread

14. Patho cntd….
• Growth of bacteria within the genitourinary system is promoted by
host factors such as;
• Vesico-ureteral reflux
• Hydronephrosis
• Obstruction
• Calculi
• Rarely, UTIs occurs by hematogenous spread- kidney abscess in staph
aureus bacteremia, candidemia, salmonella, mycobacterium;
Lymphatogenous in men- rectal and colonic lymphatic vessels to
prostate and bladder & in women- periuterine lymphatics to urinary
tract and Direct Extension i.e. PID & genitourinary tract fistulas

15. Patho cntd….
• Bacterial virulence factors in UTI
• Bacterial urease(proteus) splits urea forming ammonium ion which alkinizes urine with loss
of acid Ph.
• Gram-negative endotoxin decreases ureteral peristalsis.
• Haemolysin damages renal tubular epithelium & promotes invasive infection.
• Aerobactin of E.coli promote iron accumulation for bacterial replication
• pili, hair-like appendages on the cell surface of E. coli enable bacteria to ascend into the
bladder and kidney
• Colonization of the periurethral area by uropathogenic enteric pathogens is the
first step in the development of a UTI.
• Pathogens attach to the uroepithelial cells via an active process mediated by
glycosphingolipid receptors on the surface of epithelial cells .
• Bacterial attachment recruits toll-like receptors (TLR).
• TLR binding triggers a cytokine response, which generates a local inflammatory
response.
• In the kidney, the bacterial inoculum generates an intense inflammatory
response, which may ultimately lead to renal scarring.

16. Clinical presentation
History
• The history and clinical course of a urinary tract infection (UTI) vary with the patient's age
and the specific diagnosis.
• Risk factors: recent broad-spectrum antibiotic therapy, an anatomic anomaly, voiding
dysfunction, and constipation. Previous surgery or instrumentation of urinary tract,
Immunosuppressive Rx-eg prednisone,chemo, Prostatic enlargement &Comorbid
conditions-DM,HIV
• In neonates UTI may present with nonspecific symptoms and signs (eg, fever, irritability,
poor feeding, vomiting, poor weight gain, Jaundice). UTI is discovered as part of an
evaluation for neonatal sepsis.
• Infants(age 2 mo to 2yrs) with UTI may display the following symptoms: Poor feeding,
Fever, Vomiting, Strong-smelling urine, Abdominal pain, Irritability
• Symptoms in adults may include: Dysuria, urgency, frequency, hesitancy,dribbling,slow
stream-rarely, sensation of bladder fullness or lower abd.Discomfort, flank pain,
hematuria, fevers,chills,malaise, nausea,vomiting, sometimes lower back pain, foul
smelling,cloudy urine.

17. Physical examination
• Fever
• Tachycardia
• Inguinal adenopathy
• Abdominal and flank examination :
• Suprapubic and costovertebral angle tenderness is associated with UTI
• Enlarged bladder or kidney may indicate urinary obstruction and palpable
stool in the colon may indicate constipation, both of which predispose to UTI
• Scrotal hematoma
• Penile meatal discharge
• Prostatic tenderness

18. Investigations
• Urinalysis
Dipstick-positive proteins &nitrites indicates likelihood of infection
Urine microscopy- pyuria is defined as ≥5 WBC/high-power field
(hpf) and bacteriuria as any bacteria per hpf.
Urine culture- >50,000 cfu/ml of uropathogen organism growth.
• CBC-elevated WBCs in infection
• UECs- suspected renal involvement.
• Imaging- done if there’s hx of renal calculi, DM ,polycystic
kidneys, TB. KUB Ultrasound, MCUG, Abdominal xray.

19. TREATMENT
• Supportive- IV analgesics &antipyretics & IV fluids
• Antibiotic therapy
• levofloxacin 500mg/d IV then orally for 7-14 days or 750mg/day for 5 days
• Ciprofloxacin 500mg PO bd for 7d
• Cystitis- septrin or nitrofurantoin100mg PO BD for 7d or fosfomycin 3g single dose
or ciprofloxacin 250mg PO for 3d
• Urethritis-doxycycline 100mg bd for 7d or azithromycin 1g orally single dose or
levofloxacin 500mg PO for 7d
• Pyelonephritis, a 10- to 14-day course of broad-spectrum antibiotics parenteral.
ceftriaxone 1g IV & azithromycin 1g orally.

20. Complications
• Renal parenchymal damage
• Septicaemia
• Renal abscess
• Perinephric abscess
• Pyonephrosis
• Long-term complications of pyelonephritis are hypertension,
impaired renal function, and end-stage renal disease

21. URETHRAL STRICTURE
• Stricture; Circumscribed narrowing/stenosis of a viscus (hollow
structure) due to either scarring or deposition of abnormal tissue.
• Urethral Stricture is the diminution of the urethral caliber due to
scarring of luminal tissues or deposition of abnormal tissue in the
lumen or narrowing of the lumen of the urethra causing functional
obstruction. A urethral stricture is a scar in or around the urethra,
which can block the flow of urine, and is a result of inflammation,
injury or infection

22. CLASSIFICATION & ETIOLOGY
1. According to site:
a. Anterior urethra:
Bulbar: commonly post-gonorrheal, trauma, instrumentation
Penile: Infections, Instrumentation
Glans meatus: Infections ,Instrumentation
b. Posterior urethra:
Bladder neck: Instrumentation, TURP, Cystitis, Bladder Ca
Prostatic urethra: post-prostatectomy, instrumentation
Membranous: trauma (e.g. pelvic fractures), instrumentation
NB: Any part of urethra: follows instrumentation.

23. 2. According to etiology: congenital or acquired
a. Congenital (Rare)
• meatal stenosis,congenital puv, hypospadias epispadias
• Meatal stenosis assoc with phimosis.
• Congenital posterior urethral valves
• Hypospadias
• Epispadias

24. b. Acquired:
i) Inflammatory- post-gonorrheal, shistosomiasis, TB, urethral chancre (
syphilis, H.ducreyi)
ii) Trauma - penetrating/blunt e.g. pelvic fractures, saddle injury or penile
fracture
iii) Instrumental - indwelling catheters of large caliber, urethral endoscopy
iv) Post-operative- open prostatectomy, TURP, amputation of the penis
v) Growths- giant warts, balanitis xerotica obliterans
vi) Neoplasm: Bladder Transitional cell Ca., Penile shaft Squamous cell Ca
vii) Irradiation

25. CLINICAL FEATURES
History
• Patient is usually Young (< 40 yrs)
• Symptoms is usually Of bladder outlet obstruction (BOO):
• Complete stricture -- Acute retention
• Incomplete stricture--Lower urinary tract symptoms:
a) Voiding: Obstructive symptoms; Progressive;
- hesitancy of micturition (worse in very full bladder)
-straining to void and a poor urinary stream
-intermittent stream
- Mild dysuria
-sensation of poor bladder emptying; pt. tries again (Pis-en-deux)
-micturition is prolonged and is followed by postmicturition dribbling
-chronic retention with overflow
- episodes of near retention
- Urethrocutaneous fistulas may be present
-extravasation of urine

26. b) Storage: Irritative symptoms; dysuria
- Urinary frequency by day and night
-urgency
-urge incontinence
-nocturnal incontinence (enuresis)
Other important History:
-STIs, Penile discharge, Haematuria
-Trauma, Instrumentation, Surgery
-Family hx of BPH or Ca.Prostate, Wasting, Bone Pain, Anorexia
-Symptoms of renal failure
- Chronic d’ses e.g. DM, Parkinson’s, Alzheimer’s

27. -General Exam: Pallor, Signs of uraemia
-PA.: Palpable bladder, Palpable kidneys
-Local Exam: palpation of scarring along line of urethra, fistula in
perineum, phimosis, paraphimosis, meatal stenosis, observe the pt.
micturating.
-DRE: R/O BPH or Ca. Prostate, hemorrhoids
-difficulty in passing catheter

28. Investigations
• urinary flow rates should be determined. The patient is instructed to accumulate urine until the
bladder is full and then begin voiding; a 5-second collection of urine should be obtained during
midstream maximal flow and its volume recorded. After the patient repeats this procedure 8–10
times over several days in a relaxed atmosphere, the mean peak flow can be calculated. With
strictures creating significant problems, the flow rate will be <10 mL/s (normal 20 mL/s).
• A sequential urethrogram and voiding cystourethrogram will demonstrate the location and
extent of the stricture. Urethral fistulas and diverticula are sometimes noted. Vesical stones,
trabeculations, or diverticula may also be seen
• Urethroscopy allows visualization of the stricture. Small-caliber strictures prevent passage of the
instrument through the area. Direct visualization and sonourethrography aid in determining the
extent, location, and degree of scarring. Additional areas of scar formation adjacent to the stricture
may be detected by urethroscopy
• Ultrasound scanning to assess bladder emptying and to detect any upper tract dilatation
(hydronephrosis,hydroureter).

29. Normal Urethrogram urethrogram showing urethral
stricture

30. • Urinalysis-hematuria
• Urine culture: to rule out UTI
• U/E/Cs
• Full hemogram; to rule out uti
• RBS to R/o DM as cause of urine retention
• Cystoscopy if chronic retention

31. Complications
• Urinary tract infections, which usually respond to antibiotic treatment, although
there is a tendency for them to recur as a consequence of the increased residual
urine within the bladder.
• complications of bladder outflow obstruction- bladder calculi and upper tract
dilatation with renal impairment (rare).
• retention of urine is also rare and should be treated by suprapubic catheterisation.
• Rare complications include urethral diverticulum and paraurethral abscess,
urethrocutaneous fistulas, periurethral abscesses, urethral carcinoma, and renal
failure.

32. TREATMENT
• Dilation— Sounds, Filiforms & Followers, Bougies, Guide wire, Nelaton Catheters (Self-dilatation). Dilation of
urethral strictures is seldom curative, but it fractures the scar tissue of the stricture and temporarily enlarges the
lumen. As healing occurs, the scar tissue re-forms. Bleeding and pain are major problems caused by dilation.
• Urethrotomy under endoscopic direct vision—Lysis of urethral strictures can be accomplished using a sharp
knife attached to an endoscope. The endoscope provides direct vision of the stricture during cutting. A wire can
be passed through the stricture and used as a guide during lysis. The stricture is usually incised
circumferentially with multiple incisions.
• Urethroplasty-The simplest urethroplasty involves excision of the stenosed length of urethra and
reanastomosis of the spatulated cut ends. Urethroplasty should be considered when the stricture has arisen
following trauma and when a stricture has recurred following endoscopic treatment
• Permanent stents
• Bypass - perineal urethrotomy
- suprapubic cystotomy

33. • Supportive:
-urine evacuation (-suprapubic catheter in acute retention or trauma,
or prolonged stricture)
-Analgesics-complicated by urinary retention, UTI and stones
-Antibiotics

34. CARCINOMA OF THE BLADDER
• 95% of primary bladder tumours originate in transitional epithelium; the remainder arise from connective
tissue (angioma, myoma, fibroma and sarcoma) or are extra-adrenal phaeochromocytomas.
 Secondary tumours of the bladder are common- direct extension tumours (prostate, cervix, rectum, the uterus
or the ovaries) & metastatic tumours (melanoma, lymphoma, stomach, breast, kidney, lung)
• Histological types of bladder cancer include:
• urothelial- Over 90% are urothelial in origin.
• Squamous- Pure squamous carcinoma is uncommon (approximately 5%), except in areas where bilharzia
is endemic.
• Adenocarcinoma (or mixed, as a result of metaplasia in a transitional cell carcinoma [TCC]).- Primary
adenocarcinoma, which arises from either the urachal remnant or areas of glandular metaplasia, accounts
for 1–2% of cases.
• Rare epithelial carcinomas (villous adenomas, carcinoid tumors, carcinosarcomas and melanomas)
• Rare nonepithelial cancers [pheochromocytomas, lymphomas, choriocarcinomas, mesenchymal tumors
(hemangioma, osteogenic sarcoma, myosarcoma)]

35. Epidemiology
 Average age at diagnosis – 65 y
 The fourth most common non-dermatological malignancy in men after prostate, lung and
colorectal cancer in the US.
 Bladder cancer is the ninth most common cancer in the world, with 437,000 new cases
and 186,000 deaths diagnosed in 2016.
• M:F = 3:1 except in TCC where it is 1:2
• Women have a worse prognosis.
• Higher incidence in whites but poorer prognosis in blacks
• Highest incidence in Africa is in schistosomal-endemic areas esp Egypt and Sudan.
• Incidence is reducing in countries where smoking is decreasing and schistosomiasis is
being managed better

36. Risk Factors & Pathogenesis- bladder cancer
 Cigarette smoking is the main aetiological factor (40% of cancers).
 Occupational exposure urothelial carcinogens remains common (2-naphthylamine; 4-aminobiphenyl;
benzidine; chlornaphazine; 4-chloro-o-toluidine; methylene dianiline; benzidine-derived azo dyes)
 Occupations associated with an increased risk of bladder cancer are: textile workers; dye workers; tyre
rubber and cable workers; petrol workers; leather workers; shoe manufacturers and cleaners; painters;
hairdressers; lorry drivers; drill press operators; chemical workers; rodent exterminators and sewage
workers
 Physical trauma – infection (Schistosomiasis), instrumentation, calculi
 Radiation therapy of the pelvis
 Chemotherapy – cyclophosphamide
 Long term indwelling catheterization
 Human papillomavirus infection — especially high-risk serotypes of HPV, eg HPV 16.

37. Genetic factors
• Activation of dominantly acting oncogenes such as ras and c-erbB-1 and -2, and
transcription factors such as E2F3
• Inactivation of tumour-suppressor genes such as p53, p21, p16 and the
retinoblastoma gene.
• Lynch syndrome — Patients with Lynch syndrome (hereditary nonpolyposis
colorectal cancer) are at risk for developing urothelial malignancies, especially
those with mutations in mutS homolog 2 (MSH2).
• Genetic factors may also modify the risk associated with exogenous agents, either
through the activation or detoxification of potential carcinogens.

38. CLINICAL PRESENTATION bladder
cancer
• painless hematuria (grossly visible or microscopic). The bleeding
may give rise to clot formation and clot urinary retention
• Irritative voiding symptoms- daytime and/or nocturnal frequency,
urgency, dysuria, or urge incontinence
• Obstructive voiding symptoms. Symptoms include straining, an
intermittent stream, nocturia, decreased force of stream, and a
feeling of incomplete voiding. Less common and may be due to
tumor location at the bladder neck or prostatic urethra
• Constitutional symptoms — Symptoms such as fatigue, weight loss,
anorexia, and failure to thrive are usually signs of advanced or
metastatic disease and denote a poor prognosis

39. INVESTIGATION OF BLADDER CARCINOMA
• urinalysis should include a microscopic and gross examination as well as a dipstick. Microscopic hematuria.
• Urine cytology- Urine can be cultured and examined cytologically for malignant cells. This is not a good
screening test but a positive result is highly specific
• Cystoscopy — Cystoscopy is the gold standard for the initial diagnosis and staging of bladder cancer. It is
carried out with a rigid instrument under general anaesthesia or with a flexible instrument under local
anaesthesia Any visible tumor or suspicious lesion seen can be biopsied or resected transurethrally .
• Computed tomography scan- CT may demonstrate extravesical extension, nodal involvement in the pelvis
or retroperitoneum, visceral, pulmonary, or osseous metastasis, and tumor involvement or obstruction of the
upper urinary tract.
• Intravenous pyelogram — An IVP can visualize both the bladder and upper urinary tracts. more sensitive for
detection of small lesions of the ureter or renal pelvis.
• MRI - for staging of invasive or locally advanced disease and may be better at evaluating tumors at the base
and dome of the bladder.
• Ultrasound — is not very useful for the diagnosis or staging of bladder cancer. US can confirm the presence
of a soft tissue mass, but usually cannot determine depth of invasion, extravesical extension, or nodal
status. useful in evaluating the upper tracts for renal parenchymal disease, hydronephrosis.

40. Tumour staging
and grading
• HISTOLOGIC GRADE- WHO and the
International Society of Urological Pathology
(ISUP) classification system for urothelial
(transitional cell) neoplasms, in which urothelial
cancer is classified as low grade and high
grade based upon the degree of nuclear
anaplasia and architectural abnormalities
• Low grade tumors develop into non-muscle-invasive
tumors which account for about 80% of bladder
cancers. Minimal risk of progression to death.
• High grade tumors are invasive and have a propensity
to metastasize. Non-muscle invasive lesions invariably
progress but muscle invasive ones are lethal.
Typically, invasive urothelial cancers are high
grade.
• staging system is the TNM system, which is
based on pathologic studies of cystectomy
specimens.
• Stage is the most important independent
prognostic variable for progression and overall
survival for invasive bladder cancer.

41. TREATMENT FOR CARCINOMA OF THE BLADDER
• Primary tumors without muscle invasion (Ta and T1 lesions) are generally managed initially with
Transurethral resection.
• Patients are at significant risk of recurrence and/or progression may also require intravesical
therapy. Intravesical immunotherapy with BCG for patients with high-risk disease (Ta, Tis,
T1). Chemotherapy agents, such as mitomycin, epirubicin, and gemcitabine can also be used.
• All patients are at risk for recurrence both in the bladder and elsewhere in the urothelium, and
long-term surveillance is required following initial therapy
• Radical cystectomy with urinary diversion is the treatment of choice for patients with muscle
invasive disease.
• Neoadjuvant cisplatin-based chemotherapy improves overall survival.
• Radiotherapy- External beam radiotherapy is usually given at 60 Gy over a 4- to 6-week period.
• In patients with metastatic disease Combination chemotherapy (using platinum-based regimens
such as methotrexate, vinblastine, doxorubicin, and cisplatin [MVAC] or gemcitabine plus cisplatin
[GC] may prolong survival and often provides palliation of symptomatic disease.

42. CARCINOMA OF THE PROSTATE
• It the most common malignant tumour in men over the age of 65 years.
• 2nd most common cause of cancer death in men above age 55years (1st : cancer of the
lung)
• Responsible for approx. 3% of all deaths in men >55yrs
• >50% die within 10yrs of Diagnosis
• Lifetime risk for developing ca prostate in males >50 yrs 9.5%; risk of dying 2.9%
• increasing age heightens the risk for prostate cancer. The probability of prostate cancer
diagnosis in a man younger than 40 years is 1 in 10,000; for men 40–59 years old, it is 1
in 103; and for men 60–79 years old, it is 1 in 8.

43. Risk factors
• Increasing age
• It is more common in black than white or Hispanic men.
• About 10–15% of younger men who develop prostate cancer have a positive family
history of the disease.
• Men with family history are at a higher risk of developing cancer which may present 6-7 years
earlier.
• Genes identified in etiology:HPC1, PCAP, BRCA-2, HOXB13. Most defects are on chromosome 1.
• Men with Lynch syndrome have a two-fold increased risk
• Dietary factors:
• More risk: inc. fat, vit D def., vit A def.
• Less risk: Selenium, Vit E, Soy
• Chemical carcinogens: agricultural nitrate fertilizer or ferrochromium industry workers;
Cadmium
• Cigarette smoking

44. • Prostate cancer develops when
the rates of cell division exceed
those of cell death, leading to
uncontrolled tumor growth.
• Following the initial
transformation event, further
mutations of a multitude of
genes, including the genes for
p53 and retinoblastoma, can lead
to tumor progression and
metastasis
• Approximately 60–70% of cases of
prostate cancer originate in the
peripheral zone
• 10–20% originate in the transition
zone
• 5–10% originate in the central zone.
Schematic lateral view
of the prostate
Transverse view
Cut section

45. Pathology
• 95% of prostate cancers are adenocarcinomas while SCC are <1%.
• SCC and TCC are more common in men who have had previous radiation therapy
for prostate cancer.
• Routes of spread:
• Local spread : seminal vesicles, the bladder neck, trigone, later ureters,rectum.
• Bloodstream : Bone; pelvic bones, lower lumbar vertebrae, femoral head, rib
cage and skull.
• Lymphatic : may occur
i) Lym passing to the obturator fossa.
ii) Lym over the seminal vesicles to drain into the external iliac lymph nodes

46. Clinical presentation
• It is rare for patients to present because of symptoms attributable to
prostate cancer. Most prostate cancers are diagnosed in the local stage
and are asymptomatic.
• Prostate cancer may present with nonspecific urinary symptoms,
hematuria-these symptoms are more commonly due to nonmalignant
conditions.
• Manifestations of metastatic and advanced prostate cancer may include the
following:
• Weight loss and loss of appetite
• Anemia
• Bone pain, with or without pathologic fracture
• Neurologic deficits from spinal cord compression
• Lower extremity pain and edema due to obstruction of venous and lymphatic tributaries by
nodal metastasis
• Uremic symptoms can occur from urethral obstruction caused by local prostate growth or
retroperitoneal adenopathy secondary to nodal metastasis.

47. physical examination
• Digital rectal examination —
• may detect prostate nodules
• Asymmetry.
• Irregular induration, characteristically stony hard in part or in the whole of the gland
(with obliteration of the median sulcus)
• Obliteration of median sulcus
• Features Diagnostic ca
• Extension beyond capsule
• Deformity
• Projection outwards of capsule
• DRE can only detect tumors in the posterior and lateral aspects of the
prostate gland- palpable via the rectum.

48. Investigations
• Prostate-Specific Antigen
• PSA is used as a diagnostic (screening) tool.
• It is prostate-specific, not prostate cancer-specific BPH and prostatitis, urethral
instrumentation and perineal insults such as prolonged bike riding—can elevate the PSA,
producing false-positive results.
• The positive predictive value of a serum PSA between 4 and 10 ng/mL is approximately
20–30%. For levels >10 ng/mL, the positive predictive value increases from 42% to 71.4%
.
• They are age-related values. In men aged 50–69 years, a level of about 3–4 ng/mL need
prostate biopsy.
• Prostate-specific antigen density is the level of serum PSA divided by the prostate
volume. The higher the PSA density, the more likely it is that the PCa is clinically
significant
• Prostate Biopsy
• Indications are an elevated serum PSA &/or abnormal DRE
• A transrectal biopsy or transperineal approach is typically performed with imaging
guidance
• The diagnosis of prostate cancer is based on the histology of tissue obtained on prostate
biopsy. A biopsy may show prostate cancer or precancerous or benign findings.
• architectural features of the cells in the biopsy tissue are used to generate a Gleason
grade.

49. GRADING
• The Gleason system is the most commonly
employed grading system.
• The system relies on the low-magnification
appearance of the glandular architecture under
the microscope.
• In determining the grade of a given tumor,
pathologists assign a primary grade to the pattern
of cancer that is most commonly observed and a
secondary grade to the second most commonly
observed pattern in the specimen.
• Grades traditionally ranged from 1 to 5 .
• The Gleason score or Gleason sum is obtained
by adding the primary and secondary grades
together
• Gleason grades
2-4: well differentiated
5-6: moderately differentiated
8-10: poorly differentiated
7: s’times moderately, s’times poorly.
• Important in placing patients in prognostic groups

50. TNM staging system
for prostate cancer
• Primary tumor categorization (T stage),
the clinical staging system uses results of
the DRE.
 T1 and T2
-The progression rate of well-differentiated
T1a prostate cancer is very low: 10–14%
after eight years. For moderately
differentiated tumours, the rate is about 20%
-For T1b and T2 tumours, the rate is in
excess of 35%
 T3 and T4 (MO)- About 50% progress to
bony metastases after 3–5 years
 M1- The median survival of men with
metastatic disease is about 3 years

51. • Urinalysis -hematuria or infection
• CBC- leucoerythroblastic anaemia secondary to extensive marrow
invasion, or anaemia may be secondary to renal failure.
• Liver function tests- abnormal if there is extensive metastatic
invasion of the liver.
• Alkaline phosphatase-may be raised from either hepatic involvement
or secondaries in the bone.
• U/E/Cs- Azotemia can result from bilateral ureteral obstruction either
from direct extension into the trigone or from retroperitoneal
adenopathy

52. • Transrectal ultrasound-(TRUS)
• can be an excellent modality to both identify and stage prostate cancers,
• TRUS biopsy
• prostate cancer tends to appear as a hypoechoic lesion in the peripheral zone and/or hypervascularity seen on power
Doppler examination
• Magnetic resonance imaging (MRI)-
• most accurate method of staging local disease
• useful for identifying anterior lesions that are more difficult to detect by TRUS and is increasingly used to augment prostate
biopsy.
• bone scan-
• 99mTc-Bone scan has been the most widely used method for evaluating bone metastases.
• It is more sensitive in the diagnosis of metastases than a skeletal survey, but false positives occur in areas of arthritis,
osteomyelitis or a healing fracture
• Positron emission tomography (PET) imaging
• Identifying a metastasis
• Axial imaging (CT, MRI)—
• Cross-sectional imaging of the pelvis is selectively performed to exclude lymph node metastases in high-risk patients

53. Treatment
Localized Disease
• Incidentally diagnosed T1a and T1b disease.
• Men in 70’s conservative treatment
• Men in < 65 Radical surgical treatment
• Radical prostatectomy- be carried out only in men with a life expectancy of >10 years. A wide excision
approach can give clear surgical margins in T3a disease. The most widely used surgical techniques are the
open retropubic radical prostatectomy and a minimally invasive radical prostatectomy.
• Pelvic node dissection
• Radiation therapy — external beam RT and brachytherapy can used as a single modality for clinically
localized, low-risk prostate cancer
• Ablation therapy — Cryotherapy, high-intensity focused ultrasound (HIFU), and photodynamic therapy have
been used to selectively destroy prostate tissue. Not widely used.
• Follow-up surveillance after initial definitive treatment is an important component of patient management.
Although most patients with low-risk, clinically localized prostate cancer will remain disease free, a minority
will relapse with local and/or distant disease.

54. • Advanced D’se- (locally advanced & metastatic d’se)
Androgen ablation:
• Orchidectomy- T3,4, M
• Medical
• Estrogen- DES 3mg/d (1mg=too low; 5mg has CVS toxicity)
• LHRH agonists/analogs - leuprolide (1mg/d sc), goserelin (3.6mg sc q28days/10.8mg sc
q12wks), nafarelin
• Anti-androgens Anti-androgens-flutamide, (750mg/d in 3 divided doses) bicalutamide (with
LHRH agonist, 50mg OD at same time)
• Failed or Relapse of Hormone Therapy
• Medical: Hydrocortisone- pain relief
• Radiotherapy: External beam, Brachy therapy
• Cytotoxic chemotherapy (metastasis)- Objective response rates <30% . Palliative care.
 Cyclophosphamide, 5-fluorouracil, Methotrexate
 Estramustine phosphate, Prednimustine, Cisplastin

55. PROGNOSIS
• With early Diagnosis & Treatment should be curable.
• Advanced disease favorable if endocrine sensitive.
• Advanced unresponsive disease progresses in 18 months
Causes of death
• Thrombophlebitis with fatal pulmonary embolism
• DIC - lethal hemorrhage
• Severe cachexia - debilitation

56. TESTICULAR TUMORS
• The most common solid malignant tumor in men aged 20-35.
• Median age is 33 years.
• Maldescent of the testis contributes to its occurrence.
• Classified according to the predominant cellular type:
o germ cell tumours (90–95% per cent) (these include seminoma (40%), embryonal cell
carcinoma, yolk sac tumor, teratoma (32%), and choriocarcinoma);
o interstitial tumours (1–2 per cent) (these include Leydig cell tumours);
o lymphoma (3–7 per cent);
o other tumours (1–2 per cent).
• Highest rates in Northern Europe. Lowest in Asia and Africa.
• Incidence is highest in whites but blacks have a worse prognosis.
• Generally highly curable.

57. Risk factors: testicular tumors
oCryptochirdism – increases risk fourfold to eightfold. Orchiopexy reduces the
risk. Tumor can develop even in the well descended testis.
oPrevious Hx of testicular cancer – increases risk 500-fold. 1-2% of patients will
return with a second contralateral cancer.
oGenetics – people with Klinefelter’s syndrome, Down’s syndrome, mullerian
syndrome, testicular feminization, and gonadal dysgenesis have increased
risk.
oFamily Hx – brothers have a 8-10-fold risk while sons have a 2-4-fold risk.
oInfertility – men with male factor infertility are 3 times more likely to develop
subsequent cancer.
oEnvironmental exposure – exposure to DES in utero.

58. • Pure seminomas account for 50% of pure germ
cell tumors. Serum markers are normal except if
there is syncytiotrophoblastic germ cells are
present then beta-hCG is increased.
• Embryonal carcinomas constitute 2% of all germ
cell tumors but are found in 85% of mixed
tumors.
• Teratomas are generally benign but have the
potential for metastasis. They have elements of
all 3 germ layers.
• Choriocarcinomas are the least common but
they are very aggressive. Hematological
metastasis are very common. Associated with
elevated beta-hCG.
• Yolk cell/endodermal sinus tumors are common
in chldren. In adults, elements are found in 40%
of mixed tumors. Associaed with elevated AFP.
• Mixed germ cell tumors constitute a third of
testicular cancers and behave like
nonseminomas.

59. Staging
• TNM staging is the most widely used
system for the staging.
• The older staging system of Stages I-
IV is still considered valuable in
determining the treatment options.
The stages are:
• Stage I: Tumour is confined to the
testis and epididymis.
• Stage II: Nodal disease is present
but is confined to nodes below the
diaphragm.
• Stage III: Nodes are present above
the diaphragm.
• Stage IV: Non lymphatic metastatic
disease (most typically within the
lungs).

60. Clinical presentation
• painless testicular lump.
• A sensation of heaviness in the testis
• Few patients experience pain. Some patients can present with
severe pain and acute enlargement of the testis because of
haemorrhage into the tumour.
• symptoms of metastatic disease.: abdominal or lumbar pain. Lung
metastases can cause chest pain, dyspnoea and haemoptysis.
• Examination: intratesticular solid mass.
• Rectal examination is normal.
• Around 5% of cases have gynaecomastia.
• In 1–2% of cases the tumour is bilateral.

61. Investigations
• Ultrasound scanning of the testis-
• It is a mandatory test in all suspected cases of testicular tumour. Also assess
the contralateral testis.
• Levels of tumour markers- raised in around 50% of cases.
• AFP
• hCG.
• Used to monitor the response to treatment.
• Chest x-ray – may demonstrate the ‘classical’ cannon ball metastases
• Computed tomography (CT) of chest, abdomen and pelvis- detecting
metastatic disease and for monitoring the response to therapy

62. Treatment
• Whenever possible, a baseline sperm count and sperm banking
should be performed prior to diagnosis and staging. Semen
cryopreservation should be made available to all men prior to
instituting therapy if they wish to preserve fertility.
• Stage I —orchiectomy is usually curative.
• Stage II — orchiectomy, radiotherapy &/or cisplatin-based
combination chemotherapy.
• Advanced disease- cisplatin-based combination chemotherapy or
bleomycin, etoposide, and cisplatin (BEP) or etoposide and cisplatin.
• Periodic surveillance of beta-hCG & AFP for detecting early relapse.

63. PENILE CANCER
• Carcinoma of the penis is most typically a squamous cell carcinoma
arising in the skin of the glans (48%) or the prepuce (21%)
• They present either as an induration, papule or ulceration.
• Circumcised males rarely develop penile cancer.
• It is a slow-growing cancer so most patients present late.
• Spontaneous regression does not occur.
• It account for 0.4-0.6% of all tumors in Europe and the USA but it’s
higher in Asia, Africa and South America.

64. Risk factors
• Phimosis is present in 25-75% of men with the disease.
• Circumcision has been shown to be an effective prophylactic measure
particularly when done in neonates.
• Pre-malignant lesions that may evolve into cancer: cutaneous horns,
bowenoid papulosis, giant condyloma.
• CIS on the glans is called erythema of Queyrat but when it occurs on the
shaft it’s called Bowen disease.
• Other risk factors:
o HPV-16 and HPV-18 have been found in one third of cases.
o Cigarette smoking and chewing tobacco
o History of chronic balanitis, priapism, phimosis
o Penile trauma involving the prepuce

65. Penile intraepithelial neoplasia
(carcinoma in situ of the penis,
Bowen’s disease, erythroplasia of
Queyrat)
• It is typically seen as a red cutaneous
patch on the penis
• When it occurs on the glans penis, it
is known as erythroplasia of Queyrat
• when it occurs on the shaft of the
penis it is called Bowen’s disease.
• biopsy is indicated for diagnosis
• Treatment is by means of topical 5-
FU cream, CO2 laser ablation or
surgical excision.
Penile intraepithelial
neoplasia affecting the glans
penis (as erythroplasia of
Queyrat).

66. • It is generally a disease of older men. Incidence increases in men above age
60 but peaks at age 80. About 10% of patients are under 40 years of age
• Begin as small lesions that gradually grow laterally before invading the
corpora and the shaft.
• Penile auto amputation may occur if left untreated.
• Tumors >5cm and involving >75% of the shaft are associated with higher
rates of nodal metastasis and lower survival rate.
• Nodal metastasis: femoral & inguinal > supf inguinal > deep inguinal >
pelvic > cross connections (bilateral involvement) > distant metastasis:
lungs, liver, bone, brain.
• Secondary infection causes a foul, bloody discharge.

67. Pathology
• Carcinoma of the penis is most
typically a squamous cell carcinoma
arising in the skin of the glans penis
or the prepuce. It may be flat and
infiltrating or warty in appearance.
• T1 tumours are confined to the skin,
with T2 tumours invading the
corpus spongiosum or the corpus
cavernosum. T3 tumours invade the
urethra and T4 tumours invade
adjacent structures. The earliest
lymphatic spread is to the inguinal
(N1 and N2 disease) and then to the
iliac nodes (N3 disease). Distant
metastatic deposits are infrequent.
WHO
classification
Grade 1 Well differentiated, 33% undifferentiated
cells
Grade 2 Moderately differentiated, 33-66%
undifferentiated cells
Grade 3 Poorly differentiated, >66% undifferentiated
cells

68. A late presenting squamous cell cancer of the penis.
A squamous cell cancer arising from the inner aspect
of the prepuce

69. Treatment
• Primary tumour- surgical excision is the mainstay of treatment.
• Penile preserving surgery with excision of much lower margins of normal tissue.
• Tumours affecting the glans penis require glansectomy.
• In advanced cases, total penectomy is required with formation of a perineal urethrostomy.
• Pelvic nodes management - pelvic lympadenectomy or radiotherapy
• Chemotherapy- palliation in those with metastatic disease. platinum-based chemotherapy
• The prognosis for tumours confined to the penis is good with 5-year survival rates in excess of
80%. With nodal involvement the 5-year survival rate falls to around 40%.
• Penile cancer has a progressive course that can be fatal within 2 years if untreated.

70. Benign prostatic hyperplasia (BPH)
• BPH is a histologic diagnosis defined as an increase in the total
number of stromal and glandular epithelial cells within the
transition zone of the prostate gland. This hyperplasia causes
formation of large, discrete prostatic nodules.
• BPH results in benign prostatic enlargement (BPE) in some,
but not all men. This enlargement can, in turn, lead to benign
prostatic obstruction (BPO) and bladder outlet obstruction
(BOO). While BPH alone does not require treatment, BPE and
BPO are often associated with lower urinary tract symptoms
(LUTS), which may require treatment.

71. Epidemiology
• Prevalence — increases with age. 20% in men aged 41–50
years, to 50% in men aged 51–60 years, and upto 90% in men
older than 80 years.
• Genetic susceptibility –familial tendencies towards BPH &
diagnosis at an earlier age than sporadic BPH.
• Race – more common in Blacks than White men.

72. Aetiology
• Multifactorial
• Hormones- Serum testosterone levels slowly but significantly
decrease with advancing age; however, levels of oestrogenic steroids
are not decreased equally. According to this theory, the prostate
enlarges because of increased oestrogenic effects.
• Age-the mesenchymal theory that apoptosis of cells is slowed in favor
of cell proliferation with advancing age
• Increased risk of BPH may be related to inflammation and
metabolic factors- Obesity-related inflammation, autoimmune
processes, and chronic infection.

73. Pathology
• The prostate is composed of both stromal and epithelial elements.
• BPH affects both glandular epithelium and connective tissue stroma to variable degrees
• BPH develops primarily in the periurethral or transitional zone of the prostate. The hyperplastic
nodules are comprised primarily of stromal components and, to a lesser degree, epithelial cells.
• As BPH nodules in the transition zone enlarge, they compress the outer zones of the prostate,
resulting in the formation of a so-called surgical capsule. This boundary separates the transition
zone from the peripheral zone and serves as a surgical plane for enucleation of the prostate during
open simple prostatectomies or holmium laser enucleation of the prostate procedures.

74. Pathophysiology
• The symptoms of BPH are either due to the obstructive component of the prostate or the secondary response
of the bladder to outlet resistance caused by the enlarged gland.
• The obstructive component can be subdivided into mechanical and dynamic forms of obstruction.
• As prostatic enlargement occurs, mechanical obstruction may result from intrusion into the urethral
lumen or bladder neck, leading to a higher bladder outlet resistance.
• Dynamic obstruction- The prostatic stroma, composed of smooth muscle and collagen, is rich in
adrenergic nerve supply. The level of autonomic stimulation thus sets a tone to the prostatic urethra. This
explains the variable nature of the symptoms experienced by patients.
• Secondary response of the bladder to the increased outlet resistance- causes irritative voiding complaints of
• If BPH causes BOO, the musculature of the bladder hypertrophies to overcome the obstruction and
appears trabeculated. Significant BPH is associated with increased blood flow, and the resultant veins at
the base of the bladder are apt to cause haematuria.

75. Clinical presentation
• BPH may presents with lower urinary tract symptoms (LUTS).:
• Obstructive(voiding) symptoms include hesitancy, decreased force and caliber of
stream, intermittent stream – stops and starts, sensation of incomplete bladder emptying,
straining to urinate, and postvoid dribbling.
• Irritative(storage) symptoms include urgency, frequency, and nocturia, urge
incontinence and nocturnal incontinence (enuresis).
• General physical examination - signs of chronic renal impairment with anaemia and
dehydration.
• Abdominal examination- distended bladder may be found on palpation
• DRE- BPH usually results in a smooth, firm, non-tender, elastic enlargement of the prostate
• The nervous system is examined to eliminate a neurological lesion.

76. Complications
Complications of untreated BPH include
• acute urinary retention.
• chronic obstruction and failure to completely empty the bladder of
urine can increase the risk of urinary tract infections (UTIs), bladder
stones, formation of bladder diverticuli, and renal damage.
• BPH is not a risk factor for prostate cancer. BPH occurs primarily in
the central or transitional zone of the prostate, whereas prostate cancer
originates primarily in the peripheral part of the gland.

77. DIFFERENTIAL DIAGNOSIS
• Urethral stricture
• Bladder neck contracture
• Prostate cancer.
• Urinary tract infection
• Neurogenic bladder
• Bladder cancer

78. Investigations
• urinalysis to exclude infection or hematuria
• Renal fuction tests- Renal insufficiency may be observed in 10% of patients.
• Serum PSA –optional
• renal ultrasound or computed tomography - complications from BPH (eg,
hematuria, urinary tract infection, renal insufficiency, history of stone disease).
• TRUS is useful to determine prostate size for men planning to undergo prostate
surgery.
• cystoscopy may be useful to identify a high bladder neck, urethral stricture, or
other pathology. If BPH is associated with hematuria, then cystoscopy is mandatory
to rule out other bladder pathology
• urodynamic profiles- Measurement of flow rate, determination of postvoid
residual urine, and pressure–flow studies. To exclude neurologic disease.

79. Treatment
Conservative treatment
• In men with relatively mild symptoms
• lifestyle interventions- avoiding fluids prior to bedtime
Medical Therapy
• Alpha-adrenergic blocking agents inhibit the contraction of smooth muscle that is found in the prostate.
prazosin, alfuzosin, Terazosin, doxazosin, tamsulosin, extended-release alfuzosin, silodosin.
• 5α-reductase inhibitors, which inhibit the conversion of testosterone to DHT, the most active form of
androgen. Finasteride, dutasteride
Surgical Therapy
• Transurethral resection of the prostate (TURP)
• Simple (subtotal) prostatectomy

80. THANKYOU
References
1.) Bailey and Love's short practice of surgery
2.) Uptodate
3.) MedScape