- •Hematuria II: causes and investigation
- •Hematospermia
- •Lower urinary tract symptoms (LUTS)
- •Nocturia and nocturnal polyuria
- •Flank pain
- •Urinary incontinence in adults
- •Genital symptoms
- •Abdominal examination in urological disease
- •Digital rectal examination (DRE)
- •Lumps in the groin
- •Lumps in the scrotum
- •2 Urological investigations
- •Urine examination
- •Urine cytology
- •Radiological imaging of the urinary tract
- •Uses of plain abdominal radiography (KUB X-ray—kidneys, ureters, bladder)
- •Intravenous pyelography (IVP)
- •Other urological contrast studies
- •Computed tomography (CT) and magnetic resonance imaging (MRI)
- •Radioisotope imaging
- •Post-void residual urine volume measurement
- •3 Bladder outlet obstruction
- •Regulation of prostate growth and development of benign prostatic hyperplasia (BPH)
- •Pathophysiology and causes of bladder outlet obstruction (BOO) and BPH
- •Benign prostatic obstruction (BPO): symptoms and signs
- •Diagnostic tests in men with LUTS thought to be due to BPH
- •Why do men seek treatment for their symptoms?
- •Watchful waiting for uncomplicated BPH
- •Medical management of BPH: combination therapy
- •Medical management of BPH: alternative drug therapy
- •Minimally invasive management of BPH: surgical alternatives to TURP
- •Invasive surgical alternatives to TURP
- •TURP and open prostatectomy
- •Indications for and technique of urethral catheterization
- •Indications for and technique of suprapubic catheterization
- •Management of nocturia and nocturnal polyuria
- •High-pressure chronic retention (HPCR)
- •Bladder outlet obstruction and retention in women
- •Urethral stricture disease
- •4 Incontinence
- •Causes and pathophysiology
- •Evaluation
- •Treatment of sphincter weakness incontinence: injection therapy
- •Treatment of sphincter weakness incontinence: retropubic suspension
- •Treatment of sphincter weakness incontinence: pubovaginal slings
- •Overactive bladder: conventional treatment
- •Overactive bladder: options for failed conventional therapy
- •“Mixed” incontinence
- •Post-prostatectomy incontinence
- •Incontinence in the elderly patient
- •Urinary tract infection: microbiology
- •Lower urinary tract infection
- •Recurrent urinary tract infection
- •Urinary tract infection: treatment
- •Acute pyelonephritis
- •Pyonephrosis and perinephric abscess
- •Other forms of pyelonephritis
- •Chronic pyelonephritis
- •Septicemia and urosepsis
- •Fournier gangrene
- •Epididymitis and orchitis
- •Periurethral abscess
- •Prostatitis: presentation, evaluation, and treatment
- •Other prostate infections
- •Interstitial cystitis
- •Tuberculosis
- •Parasitic infections
- •HIV in urological surgery
- •6 Urological neoplasia
- •Pathology and molecular biology
- •Prostate cancer: epidemiology and etiology
- •Prostate cancer: incidence, prevalence, and mortality
- •Prostate cancer pathology: premalignant lesions
- •Counseling before prostate cancer screening
- •Prostate cancer: clinical presentation
- •PSA and prostate cancer
- •PSA derivatives: free-to-total ratio, density, and velocity
- •Prostate cancer: transrectal ultrasonography and biopsies
- •Prostate cancer staging
- •Prostate cancer grading
- •General principles of management of localized prostate cancer
- •Management of localized prostate cancer: watchful waiting and active surveillance
- •Management of localized prostate cancer: radical prostatectomy
- •Postoperative course after radical prostatectomy
- •Prostate cancer control with radical prostatectomy
- •Management of localized prostate cancer: radical external beam radiotherapy (EBRT)
- •Management of localized prostate cancer: brachytherapy (BT)
- •Management of localized and radiorecurrent prostate cancer: cryotherapy and HIFU
- •Management of locally advanced nonmetastatic prostate cancer (T3–4 N0M0)
- •Management of advanced prostate cancer: hormone therapy I
- •Management of advanced prostate cancer: hormone therapy II
- •Management of advanced prostate cancer: hormone therapy III
- •Management of advanced prostate cancer: androgen-independent/ castration-resistant disease
- •Palliative management of prostate cancer
- •Prostate cancer: prevention; complementary and alternative therapies
- •Bladder cancer: epidemiology and etiology
- •Bladder cancer: pathology and staging
- •Bladder cancer: presentation
- •Bladder cancer: diagnosis and staging
- •Muscle-invasive bladder cancer: surgical management of localized (pT2/3a) disease
- •Muscle-invasive bladder cancer: radical and palliative radiotherapy
- •Muscle-invasive bladder cancer: management of locally advanced and metastatic disease
- •Bladder cancer: urinary diversion after cystectomy
- •Transitional cell carcinoma (UC) of the renal pelvis and ureter
- •Radiological assessment of renal masses
- •Benign renal masses
- •Renal cell carcinoma: epidemiology and etiology
- •Renal cell carcinoma: pathology, staging, and prognosis
- •Renal cell carcinoma: presentation and investigations
- •Renal cell carcinoma: active surveillance
- •Renal cell carcinoma: surgical treatment I
- •Renal cell carcinoma: surgical treatment II
- •Renal cell carcinoma: management of metastatic disease
- •Testicular cancer: epidemiology and etiology
- •Testicular cancer: clinical presentation
- •Testicular cancer: serum markers
- •Testicular cancer: pathology and staging
- •Testicular cancer: prognostic staging system for metastatic germ cell cancer
- •Testicular cancer: management of non-seminomatous germ cell tumors (NSGCT)
- •Testicular cancer: management of seminoma, IGCN, and lymphoma
- •Penile neoplasia: benign, viral-related, and premalignant lesions
- •Penile cancer: epidemiology, risk factors, and pathology
- •Squamous cell carcinoma of the penis: clinical management
- •Carcinoma of the scrotum
- •Tumors of the testicular adnexa
- •Urethral cancer
- •Wilms tumor and neuroblastoma
- •7 Miscellaneous urological diseases of the kidney
- •Cystic renal disease: simple cysts
- •Cystic renal disease: calyceal diverticulum
- •Cystic renal disease: medullary sponge kidney (MSK)
- •Acquired renal cystic disease (ARCD)
- •Autosomal dominant (adult) polycystic kidney disease (ADPKD)
- •Ureteropelvic junction (UPJ) obstruction in adults
- •Anomalies of renal ascent and fusion: horseshoe kidney, pelvic kidney, malrotation
- •Renal duplications
- •8 Stone disease
- •Kidney stones: epidemiology
- •Kidney stones: types and predisposing factors
- •Kidney stones: mechanisms of formation
- •Evaluation of the stone former
- •Kidney stones: presentation and diagnosis
- •Kidney stone treatment options: watchful waiting
- •Stone fragmentation techniques: extracorporeal lithotripsy (ESWL)
- •Intracorporeal techniques of stone fragmentation (fragmentation within the body)
- •Kidney stone treatment: percutaneous nephrolithotomy (PCNL)
- •Kidney stones: open stone surgery
- •Kidney stones: medical therapy (dissolution therapy)
- •Ureteric stones: presentation
- •Ureteric stones: diagnostic radiological imaging
- •Ureteric stones: acute management
- •Ureteric stones: indications for intervention to relieve obstruction and/or remove the stone
- •Ureteric stone treatment
- •Treatment options for ureteric stones
- •Prevention of calcium oxalate stone formation
- •Bladder stones
- •Management of ureteric stones in pregnancy
- •Hydronephrosis
- •Management of ureteric strictures (other than UPJ obstruction)
- •Pathophysiology of urinary tract obstruction
- •Ureter innervation
- •10 Trauma to the urinary tract and other urological emergencies
- •Renal trauma: clinical and radiological assessment
- •Renal trauma: treatment
- •Ureteral injuries: mechanisms and diagnosis
- •Ureteral injuries: management
- •Bladder and urethral injuries associated with pelvic fractures
- •Bladder injuries
- •Posterior urethral injuries in males and urethral injuries in females
- •Anterior urethral injuries
- •Testicular injuries
- •Penile injuries
- •Torsion of the testis and testicular appendages
- •Paraphimosis
- •Malignant ureteral obstruction
- •Spinal cord and cauda equina compression
- •11 Infertility
- •Male reproductive physiology
- •Etiology and evaluation of male infertility
- •Lab investigation of male infertility
- •Oligospermia and azoospermia
- •Varicocele
- •Treatment options for male factor infertility
- •12 Disorders of erectile function, ejaculation, and seminal vesicles
- •Physiology of erection and ejaculation
- •Impotence: evaluation
- •Impotence: treatment
- •Retrograde ejaculation
- •Peyronie’s disease
- •Priapism
- •13 Neuropathic bladder
- •Innervation of the lower urinary tract (LUT)
- •Physiology of urine storage and micturition
- •Bladder and sphincter behavior in the patient with neurological disease
- •The neuropathic lower urinary tract: clinical consequences of storage and emptying problems
- •Bladder management techniques for the neuropathic patient
- •Catheters and sheaths and the neuropathic patient
- •Management of incontinence in the neuropathic patient
- •Management of recurrent urinary tract infections (UTIs) in the neuropathic patient
- •Management of hydronephrosis in the neuropathic patient
- •Bladder dysfunction in multiple sclerosis, in Parkinson disease, after stroke, and in other neurological disease
- •Neuromodulation in lower urinary tract dysfunction
- •14 Urological problems in pregnancy
- •Physiological and anatomical changes in the urinary tract
- •Urinary tract infection (UTI)
- •Hydronephrosis
- •15 Pediatric urology
- •Embryology: urinary tract
- •Undescended testes
- •Urinary tract infection (UTI)
- •Ectopic ureter
- •Ureterocele
- •Ureteropelvic junction (UPJ) obstruction
- •Hypospadias
- •Normal sexual differentiation
- •Abnormal sexual differentiation
- •Cystic kidney disease
- •Exstrophy
- •Epispadias
- •Posterior urethral valves
- •Non-neurogenic voiding dysfunction
- •Nocturnal enuresis
- •16 Urological surgery and equipment
- •Preparation of the patient for urological surgery
- •Antibiotic prophylaxis in urological surgery
- •Complications of surgery in general: DVT and PE
- •Fluid balance and management of shock in the surgical patient
- •Patient safety in the operating room
- •Transurethral resection (TUR) syndrome
- •Catheters and drains in urological surgery
- •Guide wires
- •JJ stents
- •Lasers in urological surgery
- •Diathermy
- •Sterilization of urological equipment
- •Telescopes and light sources in urological endoscopy
- •Consent: general principles
- •Cystoscopy
- •Transurethral resection of the prostate (TURP)
- •Transurethral resection of bladder tumor (TURBT)
- •Optical urethrotomy
- •Circumcision
- •Hydrocele and epididymal cyst removal
- •Nesbit procedure
- •Vasectomy and vasovasostomy
- •Orchiectomy
- •Urological incisions
- •JJ stent insertion
- •Nephrectomy and nephroureterectomy
- •Radical prostatectomy
- •Radical cystectomy
- •Ileal conduit
- •Percutaneous nephrolithotomy (PCNL)
- •Ureteroscopes and ureteroscopy
- •Pyeloplasty
- •Laparoscopic surgery
- •Endoscopic cystolitholapaxy and (open) cystolithotomy
- •Scrotal exploration for torsion and orchiopexy
- •17 Basic science of relevance to urological practice
- •Physiology of bladder and urethra
- •Renal anatomy: renal blood flow and renal function
- •Renal physiology: regulation of water balance
- •Renal physiology: regulation of sodium and potassium excretion
- •Renal physiology: acid–base balance
- •18 Urological eponyms
- •Index
252 CHAPTER 6 Urological neoplasia
Bladder cancer: presentation
Symptoms
The most common presenting symptom (85% of cases) is painless total hematuria. This may be initial or terminal if the lesion is at the bladder neck or in the prostatic urethra. 34% of patients >50 years of age and 10% under age 50 with macroscopic hematuria have bladder cancer. History of smoking or occupational exposure should raise suspicion for UC in the setting of hematuria.
Asymptomatic microscopic hematuria is found on routine urine sticktesting. Up to 16% of females and 4% of males have dipstick hematuria: <5% of these patients are <50 years of age, while 7–13% of those >50 years will have a malignancy.
Pain is unusual, even if the patient has obstructed upper tracts, since the obstruction and renal deterioration arise gradually. Pain may be caused by locally advanced (T4 disease).
Filling-type lower urinary tract symptoms, such as urgency or suprapubic pain occur. There is almost always microscopic or macroscopic hematuria. This so-called malignant cystitis is typical in patients with CIS.
Recurrent urinary tract infections and pneumaturia due to malignant colovesical fistula are also found. However, this is less common than benign causes such as diverticular and Crohn disease.
More advanced cases may present with lower limb swelling due to lymphatic/venous obstruction, bone pain, weight loss, anorexia, confusion, and anuria (renal failure due to bilateral ureteral obstruction).
Urachal adenocarcinomas may present with a blood or mucus umbilical discharge or a deep subumbilical mass (rare).
Signs
As most patients have superficial localized disease, signs are generally absent. General examination may reveal pallor, indicating anemia due to chronic renal impairment or blood loss in more advanced disease. Abdominal examination may reveal a suprapubic mass in the case of locally advanced disease.
Digital rectal examination may reveal a mass above or involving the prostate. A pelvic exam in females should also be performed. Although the likelihood of diagnosing bladder cancer in patients <50 years of age is low, all patients with these presenting features should be investigated.
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254 CHAPTER 6 Urological neoplasia
Bladder cancer: diagnosis and staging
After a urinary tract infection has been excluded or treated, all patients with microscopic or macroscopic hematuria require investigation of their upper tracts, bladder, and urethra. Usually, renal imaging and flexible cystoscopy with local anesthetic are first-line investigations.
CT urography (CTU) before and after IV contrast is becoming the firstline radiological investigation of hematuria. It is faster and more sensitive than ultrasound or IVP in the detection of renal (parenchymal and urothelial) and ureteral tumors.
CTU also detects some bladder tumors, but may overcall bladder wall hypertrophy as tumor and will miss flat CIS and urethral pathology. CTU cannot replace cystoscopy. If there is hydronephrosis in association with a bladder tumor, it is likely that the tumor is causing the obstruction to the distal ureter caused by muscle-invasive disease.
False-negative cytology is frequent (40–70%) in patients with papillary UC. Overall, routine urine cytology has 50% sensitivity but a high 96% specificity and is most reliable with high-grade UC and CIS. False-positive cytology can occur from infection, inflammation, instrumentation, and chemotherapy.
Fluorescent in situ hybridization (FISH) (sensitivity 77%, specificity 98%) and other tests such as NMP-22 (sensitivity 56%, specificity 85%) may be helpful in the evaluation.
If all investigations are normal, consideration should be given to “medical” causes of hematuria, such as glomerulonephritis or IGA nephropathy. In patients with persisting microscopic hematuria, especially those with associated proteinuria or hypertension, nephrology consultation should be considered.
Transurethral resection of bladder tumor (TURBT)
TURBT usually provides definitive histological diagnosis (see p. 248). This is usually undertaken under general or spinal anesthesia. Bimanual examination is mandatory before and after bladder tumor resection in order to assess size, position, and mobility.
The pathologist should report on the tumor type, grade, and stage. In particular, the presence or absence of muscularis propria should be noted, since its absence will preclude reliable T staging. Suspicious areas are biopsied separately and consideration given to random biopsies to evaluate for CIS.
The prostatic urethra is biopsied if radical reconstructive surgery such as orthotopic neobladder is under consideration. Care should be taken in resecting tumors at the dome, since intraperitoneal bladder perforation may occur, especially in women with thin-walled bladders.
Mitomycin C, given as a single dose within 24 hours of TURBT (40 mg in 40 mL of saline or sterile water), can reduce tumor recurrence but is contraindicated with bladder perforation.
BLADDER CANCER: DIAGNOSIS AND STAGING 255
Staging investigations
These are usually reserved for patients with biopsy-proven muscle-inva- sive bladder cancer unless clinically indicated, since superficial UC and CIS disease are rarely associated with metastases.
•Pelvic CT or MRI may demonstrate extravesical tumor extension or pelvic lymphadenopathy, reported if >5–8 mm in maximal diameter.
•Chest X-ray
•Isotope bone scan (positive in 5–15% of patients with muscle-invasive UC) is obtained in cases being considered for radical treatment.
•Staging lymphadenectomy (open or laparoscopic) may be indicated in the presence of CT-detected pelvic lymphadenopathy if radical treatment is under consideration. However, this is most often performed at the time of radical cystectomy.
256 CHAPTER 6 Urological neoplasia
Management of superficial UC: transurethral resection of bladder tumor (TURBT)
The diagnostic role of TURBT is discussed on p. 254. Therapeutically, a visually complete tumor resection is adequate treatment for 70% of newly presenting patients with Ta/T1 superficial disease. The remaining 30% of patients experience early recurrence, 15% with upstaging. Because of this, it is proposed that all new patients receive adjuvant treatment (see below).
Complications are uncommon and include bleeding, sepsis, bladder perforation, incomplete resection, and urethral stricture. Alternatively, transurethral laser ablation is less likely to cause bleeding, but histological sampling would be inadequate.
Follow-up after TURBT
Most urologists perform review cystoscopy at 3 months. If this demonstrates recurrence, 70% of cases will further recur. If no recurrence is evident, only 20% will further recur. If the bladder is clear at follow-up, further cystoscopies are performed at 6 months and thereafter annually until the patient is no longer fit to undergo treatment.
There is no accepted protocol for upper tract surveillance in patients with a history of bladder UC, although some urologists recommend IVP every 2 years.
Transurethral fulguration (electrosurgical or laser)
This procedure is accepted more quickly and is less morbid for ablating very small, superficial papillary recurrences.
Patients with G3T1 UC and CIS are at significantly higher risk of recurrence and 40% are upstaged. Also, some patients experience persistent symptomatic multifocal G1/2, Ta/1 recurrent UC, which requires frequent follow-up procedures. In these circumstances, adjuvant treatment is indicated (see p. 258).
Patients with high-grade (G3) disease whose biopsy material does not contain muscularis propria should be re-resected early (within a few weeks) since the possibility of muscle invasion has not been excluded. Table 6.9 summarizes the management of bladder cancer, stage by stage.
MANAGEMENT OF SUPERFICIAL UC: TURBT 257
Table 6.9 Summary of management of bladder cancer
Histology |
Risk of |
Risk of |
Further |
Urological |
|
recurrence |
stage |
treatment |
follow-up |
|
post-TURBT |
progression |
|
|
|
|
|
|
|
G1/2, Ta/1 |
30% |
10–15% |
Consider peri- |
Review |
UC |
|
|
operative single- |
cystoscopies, |
|
|
|
dose intravesical |
commencing |
|
|
|
mitomycin C |
3 months |
|
|
|
chemotherapy |
|
Persistent |
70%+ |
10–15% |
Intravesical |
Follow-up |
multifocal |
|
|
chemotherapy, |
cystoscopies, |
recurrent |
|
|
6-week doses |
commencing |
G1/2, Ta/1 |
|
|
|
3 months |
G3, T1 UC |
80% |
40% |
Intravesical BCG, |
Follow-up |
|
|
|
6-week doses |
cystoscopies, |
|
|
|
|
commencing |
|
|
|
|
6–12 weeks |
CIS (also |
80% |
40% |
called |
|
|
severe |
|
|
urothelial |
|
|
dysplasia) |
|
|
pT2/3, N0, |
Usually TUR is |
N/A |
M0 UC, |
incomplete |
|
SCC, or |
|
|
adeno- |
|
|
carcinoma |
|
|
Intravesical BCG, |
Cystoscopies |
|
6-week doses, then |
+ biopsy and |
|
maintenance |
cytology, |
|
|
commencing |
|
|
|
|
|
3 months |
|
Radical cystectomy, |
Cystoscopies |
|
radiotherapy with |
if bladder is |
|
chemotherapy |
preserved; |
|
(“bladder |
urethral |
|
preservation,” or |
washings for |
|
palliative TURBT |
cytology |
|
(if unfit for radical |
|
|
procedure) |
|
|
T4 or |
Usually TUR is N/A |
Systemic |
Palliative |
metastatic |
incomplete |
chemotherapy; |
treatment |
UC, SCC, |
|
multidisciplinary |
for local |
or adeno- |
|
team; symptom |
bladder |
carcinoma |
|
palliation |
symptoms |
|
|
|
|
258 CHAPTER 6 Urological neoplasia
Management of superficial UC: adjuvant intravesical chemotherapy and BCG
Adjuvant intravesical chemotherapy
Depending on patient and tumor characteristics, a number of patients may benefit from some form of intravesical therapy.1 Intravesical chemotherapy (e.g., mitomycin C [MMC] 40 mg in 50 mL saline) is used for G1–2, Ta or T1 tumors, and recurrent multifocal UC. MMC is an antibiotic chemotherapeutic agent that inhibits DNA synthesis. In experimental studies, it may cause regression of small papillary UC, so it should be cytotoxic for microscopic residual disease post-TURBT.
It significantly reduces the likelihood of tumor recurrence compared to that with TURBT alone, but has never been shown to prevent progression to muscle invasion and has no impact on survival. It is used either as a single dose within 24 hours of first TURBT, or weekly for 6 weeks commencing up to 2 weeks post-TURBT.
It is administered by urethral catheter and held in the bladder for 1 hour. Thiotepa is no longer used in most centers for superficial UC.
Other potential agents include doxorubicin and gemcitabine.
Toxicity of MMC
Fifteen percent of patients report transient filling-type LUTS; occasionally, dermatitis develops on the external genitalia or palms of the hands, so treatment must be stopped. Systemic toxicity is rare with MMC given the large size of the molecule and low rate of systemic absorption.
Adjuvant intravesical BCG
Bacille Calmette–Guérin (BCG) is an attenuated strain of Mycobacterium bovis. It acts as an immune stimulant, up-regulating cytokines such as IL-6 and IL-8 in the bladder wall.
BCG is given as a 6-week course for G3T1 UC and for CIS, starting at least 2 weeks post-TURBT. It is administered via a urethral catheter, 80 mg in 50 mL saline, and retained in the bladder for 1 hour. BCG should never be given sooner than 10 days after tumor resection.
BCG produces complete responses in 60–70% of patients, compared with TURBT alone. 30% do not respond, and 30% of responders relapse within 5 years. It is more effective than MMC for adjuvant treatment of G1/2,Ta/1 UC, but is not often used (except as second-line treatment occasionally) because of the additional toxicity. Two studies have suggested that BCG may delay tumor progression to muscle invasion.
Though less expensive and more effective, BCG is potentially more toxic than intravesical chemotherapy, causing irritative symptoms in nearly all patients and low-grade fever with myalgia in 25%.
1 AUA Guideline for the management of nonmuscle invasive bladder cancer: Stages Ta, T1 and TIS: 2007 Update available at: www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines/ main-reports/bladcan07. Accessed August 2009.
MANAGEMENT OF SUPERFICIAL UC 259
BCG infection (BCGosis), especially if BCG is administered in a setting of recent surgery or traumatic catheterization, can be seen in a small percentage of patients. They develop a high, persistent fever, requiring antituberculous therapy for up to 6 months with isoniazid and pyridoxine, or standard triple therapy (rifampicin, isoniazid, and ethambutol) in critically ill patients. Granulomatous prostatitis and epididymo-orchitis are rare complications.
Contraindications to intravesical BCG
•Immunosuppressed patients
•Pregnant or lactating women
•Patients with hematological malignancy
•After a traumatic catheterization
•Active UTI
Cystoscopy done too early after BCG can produce alarming-looking effects because of the generalized inflammatory response. Follow-up cystoscopy and biopsy 3 months after BCG may still reveal chronic granulomatous inflammation.
Maintenance BCG (e.g., treatment every 3 months and then every 6 months for 3 years after the initial 6-week course or monthly regimen) demonstrated a benefit for superficial UC, excluding CIS, compared with a single 6-week course.
Maintenance may be associated with a higher risk of side effects.
Recurrent G3T1 UC or CIS
A second course of BCG could be offered; 50% of patients will respond. Otherwise, proceed without delay to radical cystectomy. The latter has a cure rate of 90%.