- •Preface and Acknowledgments
- •Contents
- •Contributors
- •1: Embryology for Urologists
- •Introduction
- •Renal Development
- •Pronephros
- •Mesonephros
- •Metanephros
- •Development of the Collecting System
- •Critical Steps in Further Development
- •Anomalies of the Kidney
- •Renal Agenesis
- •Renal Aplasia
- •Renal Hypoplasia
- •Renal Ectopia
- •Renal Fusion
- •Ureteral Development
- •Anomalies of Origin
- •Anomalies of Number
- •Incomplete Ureteral Duplication
- •Complete Ureteral Duplication
- •Ureteral Ectopia
- •Embryology of Ectopia
- •Clinical Correlation
- •Location of Ectopic Ureteral Orifices – Male (in Descending Order According to Incidence)
- •Symptoms
- •Ureteroceles
- •Congenital Ureteral Obstruction
- •Pipestem Ureter
- •Megaureter-Megacystis Syndrome
- •Prune Belly Syndrome
- •Vascular Ureteral Obstructions
- •Division of the Urogenital Sinus
- •Bladder Development
- •Urachal Anomalies
- •Cloacal Duct Anomalies
- •Other Bladder Anomalies
- •Bladder Diverticula
- •Bladder Extrophy
- •Gonadal Development
- •Testicular Differentiation
- •Ovarian Differentiation
- •Gonadal Anomalies
- •Genital Duct System
- •Disorders of Testicular Function
- •Female Ductal Development
- •Prostatic Urethral Valves
- •Gonadal Duct Anomalies
- •External Genital Development
- •Male External Genital Development
- •Female External Genital Development
- •Anomalies of the External Genitalia
- •References
- •2: Gross and Laparoscopic Anatomy of the Upper Urinary Tract and Retroperitoneum
- •Overview
- •The Kidneys
- •The Renal Vasculature
- •The Renal Collecting System
- •The Ureters
- •Retroperitoneal Lymphatics
- •Retroperitoneal Nerves
- •The Adrenal Glands
- •References
- •3: Gross and Laparoscopic Anatomy of the Lower Urinary Tract and Pelvis
- •Introduction
- •Female Pelvis
- •Male Pelvis
- •Pelvic Floor
- •Urinary Bladder
- •Urethra
- •Male Urethra
- •Female Urethra
- •Sphincter Mechanisms
- •The Bladder Neck Component
- •The Urethral Wall Component
- •The External Urethral Sphincter
- •Summary
- •References
- •4: Anatomy of the Male Reproductive System
- •Testis and Scrotum
- •Spermatogenesis
- •Hormonal Regulation of Spermatogenesis
- •Genetic Regulation of Spermatogenesis
- •Epididymis and Ductus Deferens
- •Accessory Sex Glands
- •Prostate
- •Seminal Vesicles
- •Bulbourethral Glands
- •Penis
- •Erection and Ejaculation
- •References
- •5: Imaging of the Upper Tracts
- •Anatomy of the Upper Tracts and Introduction to Imaging Modalities
- •Introduction
- •Renal Upper Tract Basic Anatomy
- •Modalities Used for Imaging the Upper Tracts
- •Ultrasound
- •Radiation Issues
- •Contrast Issues
- •Renal and Upper Tract Tumors
- •Benign Renal Tumors
- •Transitional Cell Carcinoma
- •Renal Mass Biopsy
- •Renal Stone Disease
- •Ultrasound
- •Plain Radiographs and IVU
- •Renal Cystic Disease
- •Benign Renal Cysts
- •Hereditary Renal Cystic Disease
- •Complex Renal Cysts
- •Renal Trauma
- •References
- •Introduction
- •Pathophysiology
- •Susceptibility and Resistance
- •Epidemiological Breakpoints
- •Clinical Breakpoints
- •Pharmacodynamic Parameters
- •Pharmacokinetic Parameters
- •Fosfomycin
- •Nitrofurantoin
- •Pivmecillinam
- •b-Lactam-Antibiotics
- •Penicillins
- •Cephalosporins
- •Carbapenems
- •Aminoglycosides
- •Fluoroquinolones
- •Trimethoprim, Cotrimoxazole
- •Glycopeptides
- •Linezolid
- •Conclusion
- •References
- •7: An Overview of Renal Physiology
- •Introduction
- •Body Fluid Compartments
- •Regulation of Potassium Balance
- •Regulation of Acid–Base Balance
- •Diuretics
- •Suggested Reading
- •8: Ureteral Physiology and Pharmacology
- •Ureteral Anatomy
- •Modulation of Peristalsis
- •Ureteral Pharmacology
- •Conclusion
- •References
- •Introduction
- •Afferent Signaling Pathways
- •Efferent Signaling
- •Parasympathetic Nerves
- •Sympathetic Nerves
- •Vesico-Spinal-Vesical Micturition Reflex
- •Peripheral Targets
- •Afferent Signaling Mechanisms
- •Urothelium
- •Myocytes
- •Cholinergic Receptors
- •Muscarinic Receptors
- •Nicotinic Receptors
- •Adrenergic Receptors (ARs)
- •a-Adrenoceptors
- •b-Adrenoceptors
- •Transient Receptor Potential (TRP) Receptors
- •Phosphodiesterases (PDEs)
- •CNS Targets
- •Opioid Receptors
- •Serotonin (5-HT) Mechanisms
- •g-Amino Butyric Acid (GABA) Mechanisms
- •Gabapentin
- •Neurokinin and Neurokinin Receptors
- •Summary
- •References
- •10: Pharmacology of Sexual Function
- •Introduction
- •Sexual Desire/Arousal
- •Endocrinology
- •Steroids in the Male
- •Steroids in the Female
- •Neurohormones
- •Neurotransmitters
- •Dopamine
- •Serotonin
- •Pharmacological Strategies
- •CNS Drugs
- •Enzyme-inducing Antiepileptic Drugs
- •Erectile Function
- •Ejaculatory Function
- •Premature Ejaculation
- •Abnormal Ejaculation
- •Conclusions
- •References
- •Epidemiology
- •Calcium-Based Urolithiasis
- •Uric Acid Urolithiasis
- •Infectious Urolithiasis
- •Cystine-Based Urolithiasis
- •Aims
- •Who Deserves Metabolic Evaluation?
- •Metabolic Workup for Stone Producers
- •Medical History and Physical Examination
- •Stone Analysis
- •Serum Chemistry
- •Urine Evaluation
- •Urine Cultures
- •Urinalysis
- •Twenty-Four Hour Urine Collections
- •Radiologic Imaging
- •Medical Management
- •Conservative Management
- •Increased Fluid Intake
- •Citrus Juices
- •Dietary Restrictions
- •Restricted Oxalate Diet
- •Conservative Measures
- •Selective Medical Therapy
- •Absorptive Hypercalciuria
- •Thiazide
- •Orthophosphate
- •Renal Hypercalciuria
- •Primary Hyperparathyroidism
- •Hyperuricosuric Calcium Oxalate Nephrolithiasis
- •Enteric Hyperoxaluria
- •Hypocitraturic Calcium Oxalate Nephrolithiasis
- •Distal Renal Tubular Acidosis
- •Chronic Diarrheal States
- •Thiazide-Induced Hypocitraturia
- •Idiopathic Hypocitraturic Calcium Oxalate Nephrolithiasis
- •Hypomagnesiuric Calcium Nephrolithiasis
- •Gouty Diathesis
- •Cystinuria
- •Infection Lithiasis
- •Summary
- •References
- •12: Molecular Biology for Urologists
- •Introduction
- •Inherited Changes in Cancer Cells
- •VEGR and Cell Signaling
- •Targeting mTOR
- •Conclusion
- •References
- •13: Chemotherapeutic Agents for Urologic Oncology
- •Introduction
- •Bladder Cancer
- •Muscle Invasive Bladder Cancer
- •Metastatic Bladder Cancer
- •Conclusion
- •Prostate Cancer
- •Other Chemotherapeutic Drugs or Combinations for Treating HRPC
- •Conclusion
- •Renal Cell Carcinoma
- •Chemotherapy
- •Immunotherapy
- •Angiogenesis Inhibitor Drugs
- •Conclusion
- •Testicular Cancer
- •Stage I Seminoma
- •Stage I non-seminomatous Germ Cell Tumours (NSGCT)
- •Metastatic Germ Cell Tumours
- •Low-Volume Metastatic Disease (Stage II A/B)
- •Advanced Metastatic Disease
- •Salvage Chemotherapy for Relapsed or Refractory Disease
- •Conclusion
- •Penile Cancer
- •Side Effects of Chemotherapy
- •Conclusion
- •References
- •14: Tumor and Transplant Immunology
- •Antibodies
- •Cytotoxic and T-helper Cells
- •Immunosuppression
- •Induction Therapy
- •Maintenance Therapy
- •Rejection
- •Posttransplant Lymphoproliferative Disease
- •Summary
- •References
- •15: Pathophysiology of Renal Obstruction
- •Causes of Renal Obstruction
- •Effects on Prenatal Development
- •Prenatal Hydronephrosis
- •Spectrum of Renal Abnormalities
- •Renal Functional Changes
- •Renal Growth/Counterbalance
- •Vascular Changes
- •Inflammatory Mediators
- •Glomerular Development Changes
- •Mechanical Stretch of Renal Tubules
- •Unilateral Versus Bilateral
- •Limitations of Animal Models
- •Future Research
- •Issues in Patient Management
- •Diagnostic Imaging
- •Ultrasound
- •Intravenous Urography
- •Antegrade Urography and the Whitaker Test
- •Nuclear Renography
- •Computed Tomography
- •Magnetic Resonance Urography
- •Hypertension
- •Postobstructive Diuresis
- •References
- •Introduction
- •The Normal Lower Urinary Tract
- •Anatomy
- •Storage Function
- •Voiding Function
- •Neural Control
- •Symptoms
- •Flow Rate and Post-void Residual
- •Voiding Cystometry
- •Male
- •Female
- •Neurourology
- •Conclusions
- •References
- •17: Urologic Endocrinology
- •The Testis
- •Normal Androgen Metabolism
- •Epidemiological Aspects
- •Prostate
- •Brain
- •Muscle Mass and Adipose Tissue
- •Bones
- •Ematopoiesis
- •Metabolism
- •Cardiovascular System
- •Clinical Assessment
- •Biochemical Assessment
- •Treatment Modalities
- •Oral Preparations
- •Parenteral Preparations
- •Transdermal Preparations
- •Side Effects and Treatment Monitoring
- •Body Composition
- •Cognitive Decline
- •Bone Metabolism
- •The Kidneys
- •Endocrine Functions of the Kidney
- •Erythropoietin
- •Calcitriol
- •Renin
- •Paraneoplastic Syndromes
- •Hypercalcemia
- •Hypertension
- •Polycythemia
- •Other Endocrine Abnormalities
- •References
- •General Physiology
- •Prostate Innervation
- •Summary
- •References
- •Wound Healing
- •Inflammation
- •Proliferation
- •Remodeling
- •Principles of Plastic Surgery
- •Tissue Characteristics
- •Grafts
- •Flap
- •References
- •Lower Urinary Tract Symptoms
- •Storage Phase
- •Voiding Phase
- •Return to Storage Phase
- •Urodynamic Parameters
- •Urodynamic Techniques
- •Volume Voided Charts
- •Pad Testing
- •Typical Test Schedule
- •Uroflowmetry
- •Post Voiding Residual
- •Further Diagnostic Evaluation of Patients
- •Cystometry with or Without Video
- •Cystometry
- •Videocystometrography (Cystometry + Cystourethrography)
- •Cystometric Findings
- •Comment:
- •Measurements During the Storage Phase:
- •Measurements During the Voiding Phase:
- •Abnormal Function
- •Disorders of Sensation
- •Causes of Hypersensitive Bladder Sensation
- •Causes of Hyposensitive Bladder Sensation
- •Disorders of Detrusor Motor Function
- •Bladder Outflow Tract Dysfunction
- •Detrusor–Urethral Dyssynergia
- •Detrusor–Bladder Neck Dyssynergia
- •Detrusor–Sphincter Dyssynergia
- •Complex Urodynamic Investigation
- •Urethral Pressure Measurement
- •Technique
- •Neurophysiological Evaluation
- •Conclusion
- •References
- •Endoscopy
- •Cystourethroscopy
- •Ureteroscopy and Ureteropyeloscopy
- •Nephroscopy
- •Virtual Reality Simulators
- •Lasers
- •Clinical Application of Lasers
- •Condylomata Acuminata
- •Urolithiasis
- •Benign Prostatic Hyperplasia
- •Ureteral and Urethral Strictures
- •Conclusion
- •References
- •Introduction
- •The Prostatitis Syndromes
- •The Scope of the Problem
- •Category III CP/CPPS
- •The Goal of Treatment
- •Conservative Management
- •Drug Therapy
- •Antibiotics
- •Anti-inflammatories
- •Alpha blockers
- •Hormone Therapies
- •Phytotherapies
- •Analgesics, muscle relaxants and neuromodulators
- •Surgery
- •A Practical Management Plan
- •References
- •Orchitis
- •Definition and Etiology
- •Clinical Signs and Symptoms
- •Diagnostic Evaluation
- •Treatment of Infectious Orchitis
- •Epididymitis
- •Definition and Etiology
- •Clinical Signs and Symptoms
- •Diagnostic Evaluation of Epididymitis
- •Treatment of Acute Epididymitis
- •Treatment of Chronic Epididymitis
- •Treatment of Spermatic Cord Torsion
- •Fournier’s Gangrene
- •Definition and Etiology
- •Risk Factors
- •Clinical Signs and Symptoms
- •Diagnostic Evaluation
- •Treatment
- •References
- •Fungal Infections
- •Candidiasis
- •Aspergillosis
- •Cryptococcosis
- •Blastomycosis
- •Coccidioidomycosis
- •Histoplasmosis
- •Radiographic Findings
- •Treatment
- •Tuberculosis
- •Clinical Manifestations
- •Diagnosis
- •Treatment
- •Schistosomiasis
- •Clinical Manifestations
- •Diagnosis
- •Treatment
- •Filariasis
- •Clinical Manifestations
- •Diagnosis
- •Treatment
- •Onchocerciasis
- •References
- •25: Sexually Transmitted Infections
- •Introduction
- •STIs Associated with Genital Ulcers
- •Herpes Simplex Virus
- •Diagnosis
- •Treatment
- •Chancroid
- •Diagnosis
- •Treatment
- •Syphilis
- •Diagnosis
- •Treatment
- •Lymphogranuloma Venereum
- •Diagnosis
- •Treatment
- •Chlamydia
- •Diagnosis
- •Treatment
- •Gonorrhea
- •Diagnosis
- •Treatment
- •Trichomoniasis
- •Diagnosis
- •Treatment
- •Human Papilloma Virus
- •Diagnosis
- •Treatment
- •Scabies
- •Diagnosis
- •Treatment
- •References
- •26: Hematuria: Evaluation and Management
- •Introduction
- •Classification of Hematuria
- •Macroscopic Hematuria
- •Microscopic Hematuria
- •Dipstick Hematuria
- •Pseudohematuria
- •Factitious Hematuria
- •Menstruation
- •Aetiology
- •Malignancy
- •Urinary Calculi
- •Infection and Inflammation
- •Benign Prostatic Hyperplasia
- •Trauma
- •Drugs
- •Nephrological Causes
- •Assessment
- •History
- •Examination
- •Investigations
- •Dipstick Urinalysis
- •Cytology
- •Molecular Tests
- •Blood Tests
- •Flexible Cystoscopy
- •Upper Urinary Tract Evaluation
- •Renal USS
- •KUB Abdominal X-Ray
- •Intravenous Urography (IVU)
- •Computed Tomography (CT)
- •Retrograde Urogram Studies
- •Magnetic Resonance Imaging (MRI)
- •Additional Tests and Renal Biopsy
- •Intractable Hematuria
- •Loin Pain Hematuria Syndrome
- •References
- •27: Benign Prostatic Hyperplasia (BPH)
- •Historical Background
- •Pathophysiology
- •Patient Assessment
- •Treatment of BPH
- •Watchful Waiting
- •Drug Therapy
- •Interventional Therapies
- •Conclusions
- •References
- •28: Practical Guidelines for the Treatment of Erectile Dysfunction and Peyronie´s Disease
- •Erectile Dysfunction
- •Introduction
- •Diagnosis
- •Basic Evaluation
- •Cardiovascular System and Sexual Activity
- •Optional Tests
- •Treatment
- •Medical Treatment
- •Oral Agents
- •Phosphodiesterase Type 5 (PDE 5) Inhibitors
- •Nonresponders to PDE5 Inhibitors
- •Apomorphine SL
- •Yohimbine
- •Intracavernosal and Intraurethral Therapy
- •Intracavernosal Injection (ICI) Therapy
- •Intraurethral Therapy
- •Vacuum Constriction Devices
- •Surgical Therapy
- •Conclusion
- •Peyronie´s Disease (PD)
- •Introduction
- •Oral Drug Therapy
- •Intralesional Drug Therapy
- •Iontophoresis
- •Radiation Therapy
- •Surgical Therapy
- •References
- •29: Premature Ejaculation
- •Introduction
- •Epidemiology
- •Defining Premature Ejaculation
- •Voluntary Control
- •Sexual Satisfaction
- •Distress
- •Psychosexual Counseling
- •Pharmacological Treatment
- •On-Demand Treatment with Tramadol
- •Topical Anesthetics
- •Phosphodiesterase Inhibitors
- •Surgery
- •Conclusion
- •References
- •30: The Role of Interventional Management for Urinary Tract Calculi
- •Contraindications to ESWL
- •Complications of ESWL
- •PCNL Access
- •Instrumentation for PCNL
- •Nephrostomy Drains Post PCNL
- •Contraindications to PCNL
- •Complications of PCNL
- •Semirigid Ureteroscopy
- •Flexible Ureteroscopy
- •Electrohydraulic Lithotripsy (EHL)
- •Ultrasound
- •Ballistic Lithotripsy
- •Laser Lithotripsy
- •Ureteric Stents
- •Staghorn Calculi
- •Lower Pole Stones
- •Horseshoe Kidneys and Stones
- •Calyceal Diverticula Stones
- •Stones and PUJ Obstruction
- •Treatment of Ureteric Colic
- •Medical Expulsive Therapy (MET)
- •Intervention for Ureteric Stones
- •Stones in Pregnancy
- •Morbid Obesity
- •References
- •Anatomy and Function
- •Pathophysiology
- •Management
- •Optical Urethrotomy/Dilatation
- •Urethral Stents
- •Preoperative Assessment
- •Urethroplasty
- •Anastomotic Urethroplasty
- •Substitution Urethroplasty
- •Grafts Versus Flaps
- •Oral Mucosal Grafts
- •Tissue Engineering
- •Graft Position
- •Conclusion
- •References
- •32: Urinary Incontinence
- •Epidemiology and Risk Factors
- •Pathophysiology
- •Urge Incontinence
- •Conservative Treatments
- •Pharmacotherapy
- •Invasive/ Surgical Therapies
- •Stress Urinary Incontinence
- •Male SUI Therapies
- •Female SUI Therapies
- •Mixed Urinary Incontinence
- •Conclusions
- •References
- •33: Neurogenic Bladder
- •Introduction
- •Examination and Diagnostic Tests
- •History and Physical Examination
- •Imaging
- •Urodynamics (UDS)
- •Evoked Potentials
- •Classifications
- •Somatic Pathways
- •Brain Lesions
- •Cerebrovascular Accident (CVA)
- •Parkinson’s Disease (PD)
- •Multiple Sclerosis
- •Huntington’s Disease
- •Dementias
- •Normal Pressure Hydrocephalus (NPH)
- •Tumors
- •Psychiatric Disorders
- •Spinal Lesions and Pathology
- •Intervertebral Disk Prolapse
- •Spinal Cord Injury (SCI)
- •Transverse Myelitis
- •Peripheral Neuropathies
- •Metabolic Neuropathies
- •Pelvic Surgery
- •Treatment
- •Summary
- •References
- •34: Pelvic Prolapse
- •Introduction
- •Epidemiology
- •Anatomy and Pathophysiology
- •Evaluation and Diagnosis
- •Outcome Measures
- •Imaging
- •Urodynamics
- •Indications for Management
- •Biosynthetics
- •Surgical Management
- •Anterior Compartment Repair
- •Uterine/Apical Prolapse
- •Enterocele Repair
- •Conclusion
- •References
- •35: Urinary Tract Fistula
- •Introduction
- •Urogynecologic Fistula
- •Vesicovaginal Fistula
- •Etiology and Risk Factors
- •Clinical Factors
- •Evaluation and Diagnosis
- •Pelvic Examination
- •Cystoscopy
- •Imaging
- •Treatment
- •Conservative Management
- •Surgical Management
- •Urethrovaginal Fistula
- •Etiology and Presentation
- •Diagnosis and Management
- •Ureterovaginal Fistula
- •Etiology and Presentation
- •Diagnosis and Management
- •Vesicouterine Fistula
- •Etiology and Presentation
- •Diagnosis and Management
- •Uro-Enteric Fistula
- •Vesicoenteric Fistula
- •Pyeloenteric Fistula
- •Urethrorectal Fistula
- •References
- •36: Urologic Trauma
- •Introduction
- •Kidney
- •Expectant Management
- •Endovascular Therapy
- •Operative Intervention
- •Operative Management: Follow-up
- •Reno-Vascular Injuries
- •Pediatric Renal Injuries
- •Adrenal
- •Ureter
- •Diagnosis
- •Treatment
- •Delayed Diagnosis
- •Bladder and Posterior Urethra
- •Bladder Injuries: Initial Management
- •Bladder Injuries: Formal Repair
- •Anterior Urethral Trauma
- •Fractured Penis
- •Penile Amputation
- •Scrotal and Testicular Trauma
- •Imaging
- •CT-IVP (CT with Delayed Images)
- •Technique
- •Cystogram
- •Technique
- •Retrograde Urethrogram (RUG)
- •Technique
- •Retrograde Pyelogram (RPG)
- •Technique
- •One-Shot IVP
- •Technique
- •References
- •37: Bladder Cancer
- •Who Should Be Investigated?
- •Epidemiology
- •Risk Factors
- •Role of Screening
- •Signs and Symptoms
- •Imaging
- •Cystoscopy
- •Urine Tests
- •PDD-Assisted TUR
- •Pathology
- •NMIBC and Risk Groups
- •Intravesical Chemotherapy
- •Intravesical Immunotherapy
- •Immediate Cystectomy and CIS
- •Radical Cystectomy with Pelvic Lymph Node Dissection
- •sexual function-preserving techniques
- •Bladder-Preservation Treatments
- •Neoadjuvant Chemotherapy
- •Adjuvant Chemotherapy
- •Preoperative Radiotherapy
- •Follow-up After TUR in NMIBC
- •References
- •38: Prostate Cancer
- •Introduction
- •Epidemiology
- •Race
- •Geographic Variation
- •Risk Factors and Prevention
- •Family History
- •Diet and Lifestyle
- •Prevention
- •Screening and Diagnosis
- •Current Screening Recommendations
- •Biopsy
- •Pathology
- •Prognosis
- •Treatment of Prostate Cancer
- •Treatment for Localized Prostate Cancer (T1, T2)
- •Radical Prostatectomy
- •EBRT
- •IMRT
- •Brachytherapy
- •Treatment for Locally Advanced Prostate Cancer (T3, T4)
- •EBRT with ADT
- •Radical Prostatectomy
- •Androgen-Deprivation Therapy
- •Summary
- •References
- •39: The Management of Testis Cancer
- •Presentation and Diagnosis
- •Serum Tumor Markers
- •Primary Surgery
- •Testis Preserving Surgery
- •Risk Stratification
- •Surveillance Versus Primary RPLND
- •Primary RPLND
- •Adjuvant Treatment for High Risk
- •Clinical Stage 1 Seminoma
- •Risk-Stratified Adjuvant Treatment
- •Adjuvant Radiotherapy
- •Adjuvant Low Dose Chemotherapy
- •Primary Combination Chemotherapy
- •Late Toxicity
- •Salvage Strategies
- •Conclusion
- •References
- •Index
515
BladdEr cancEr
if resection was performed using PDD. Residual |
Another important prognostic factor, besides |
|
tumor rates varied from 25% to 53.1% for white |
stage, is grade. The 1973 World Health Organi- |
|
light resection and 4.5–32.7% for PDD-assisted |
sation (WHO) grading system is most commonly |
|
resection.18-20 The benefit of PDD in terms of |
used for this.23 This system discriminates well |
|
progression rates and survival still has to be |
differentiated (G1), moderately differentiated |
|
established in larger randomized trials. |
(G2),and poorly differentiated (G3) UCC.In 2004, |
|
|
the WHO and International Society of Urological |
|
Immediate Postoperative Intravesical |
Pathology (ISUP) published a new grading sys- |
|
tem in an attempt to reduce the interobserver |
||
Chemotherapy |
variability, frequently encountered in the 1973 |
|
Administration of a single intravesical instilla- |
system.24 This system differentiates between pap- |
|
illary urothelial neoplasms of low malignant |
||
tion of chemotherapy after TUR decreases the |
potential (PUNLMP) and low-grade or high- |
|
risk of tumor recurrence by 39% in patients |
grade UCC. The PUNLMP lesions lack the cyto- |
|
with Ta or T1 bladder cancer and is therefore |
logical features of malignancy, but the cells do |
|
recommended in all patients with NMIBC.21 |
show a papillary configuration. Until the system |
|
Mitomycin C (MMC) and Epirubicin are most |
is validated by more clinical trials, it is recom- |
|
commonly used and are comparable with regard |
mended to use it together with the 1973 system. |
|
to efficacy. Timing is important though; the |
The two systems are compared in Fig. 37.2. |
|
instillation should preferably be administered |
|
|
within 24 h following TUR. In case of bladder |
Re-TUR |
|
perforation or extensive TUR, it should not be |
||
administered due to the risk of local and sys- |
It has been demonstrated that bladder tumors |
|
temic complications. The rationale behind the |
||
may be understaged based on the specimen |
||
immediate postoperative instillation is to eradi- |
||
obtained from the initial TUR25 and there is a |
||
cate microscopic tumor left behind or to destroy |
||
substantial risk of residual tumor after the ini- |
||
circulating tumor cells that could implant at |
||
tial TUR.17 To improve pathologic accuracy and |
||
sites where the urothelium has been damaged, |
||
to increase local tumor control, a second or re- |
||
both factors that are believed to be responsible |
||
TUR can be performed.25 Re-TUR should be |
||
for early recurrences. |
||
considered in case of incomplete first resection, |
||
|
||
Pathology |
for example, in multiple or large tumors or when |
|
muscular tissue was not present in the pathol- |
||
Pathologic stage is one of the most important |
ogy specimen. Furthermore, it is recommended |
|
in case of high grade Ta or any T1 bladder |
||
prognostic factors for bladder cancer. Accurate |
tumor(s).10 Preferably, the re-TUR should be |
|
staging is therefore essential, since this highly |
performed 2–6 weeks after the initial TUR. It |
|
influences patient management. The 2002 |
has been shown that by doing so,the recurrence- |
|
TNM classification proposed by the Union |
free survival can be increased.26 |
|
International Contre le Cancer (UICC) is the |
|
|
most frequently used system for staging of |
|
|
bladder cancer (Table 37.1).22 Stage Ta, T1, and |
NMIBC and Risk Groups |
|
Tis (CIS) are grouped as NMIBC, whereas |
||
stages T2, T3, and T4 are grouped as muscle- |
|
|
invasive bladder cancer. The old terminology |
After primary treatment, approximately 15–70% |
|
of “superficial” bladder cancer suggests a non- |
of patients with NMIBC will develop recurrent |
|
aggressive biology and should be avoided since |
disease in the first year and 7–40% will progress |
|
some NMIBCs do behave aggressively. CIS is a |
to muscle-invasive disease in the first 5 years. |
|
flat, high-grade noninvasive UCC and is a |
Many studies have been conducted to identify |
|
highly malignant entity. Of all primary UCCs, |
prognostic factors for recurrence and progres- |
|
approximately 70–80% presents as NMIBC and |
sion to muscle-invasive disease in patients with |
|
the remainder as muscle-invasive disease. |
NMIBC, with sometimes conflicting results. The |
|
Among the NMIBC, 70% present as Ta lesions, |
EORTC-GU group has conducted a multivariate |
|
20% as T1, and 10% as CIS. |
analysis on prognostic factors in 2,596 patients |
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Practical Urology: EssEntial PrinciPlEs and PracticE
Table 37.1. 2002 tnM classification of urinary bladder cancer
Primary tumor (t) |
|
|
tX |
Primary tumor cannot be assessed |
|
t0 |
no evidence of primary tumor |
|
ta |
noninvasive papillary carcinoma |
|
tis |
carcinoma in situ:“flat tumor” |
|
t1 |
tumor invades subepithelial connective tissue |
|
t2 |
tumor invades muscle |
|
|
t2a |
tumor invades superficial muscle (inner half) |
|
t2b |
tumor invades deep muscle (outer half) |
t3 |
tumor invades perivesical tissue |
|
|
t3a |
Microscopically |
|
t3b |
Macroscopically |
t4 |
tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall |
|
|
t4a |
tumor invades prostate, uterus, or vagina |
|
t4b |
tumor invades pelvic wall or abdominal wall |
regional lymph nodes (n) |
|
|
regional nodes are those within the true pelvis; all others are distant lymph nodes. |
||
nX |
regional lymph nodes cannot be assessed |
|
n0 |
no evidence of regional lymph node metastasis |
|
n1 |
Metastasis in a single lymph node 2 cm or less in greatest dimension |
|
n2 |
Metastasis in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension; |
|
|
or multiple lymph nodes, none greater than 5 cm in greatest dimension |
|
n3 |
Metastasis in a lymph node, more than 5 cm in greatest dimension |
|
distant metastasis (M) |
|
|
MX |
distant metastasis cannot be assessed |
|
M0 |
no evidence of distant metastasis |
|
M1 |
distant metastasis |
|
Source: Reprinted from AJCC Cancer Staging Handbook, 6th ed, p. 369.
with primary NMIBC in order to develop tables to calculate the risk of recurrence and progression in an individual patient.27 This analysis revealed that the most important prognostic factors for recurrence were number of tumors, tumor size, and prior recurrence rate, whereas the most important prognostic factors for progression were stage, presence of concomitant CIS, and grade. A scoring system was developed based on these six factors, in order to calculate the total scores for recurrence and progression
in an individual patient (Table 37.2). These total scores correspond to a certain risk for recurrence and progression at 1 and 5 years (Table 37.3). Based on these risk tables, low-, intermediate-, and high-risk groups can be defined (last column of Table 37.3). These individualized risk tables can help the urologist in making management decisions. However, these risk tables have not yet been validated externally. Furthermore, 20% of patients from the analysis initially received no treatment, less than
517
BladdEr cancEr
PUNLMP |
|
Low grade |
|
High grade |
WHO 2004 |
|
|
|
|
|
|
Grade 1 |
|
Grade 2 |
|
Grade 3 |
WHO 1973 |
Figure 37.2. Histologic spectrum of Ucc, comparison of the WHo 1973 and WHo 2004 grading systems.
Table 37.2. Eortc risk tables for nMiBc: weights used to calculate the recurrence and progression scores
Factor |
Recurrence |
Progression |
number of tumors |
|
|
single |
0 |
0 |
2–7 |
3 |
3 |
³8 |
6 |
3 |
tumor size |
|
|
<3 cm |
0 |
0 |
³3 cm |
3 |
3 |
Prior recurrence rate |
|
|
Primary |
0 |
0 |
£1 recurrence/year |
2 |
2 |
>1 recurrence/year |
4 |
2 |
t category |
|
|
ta |
0 |
0 |
t1 |
1 |
4 |
cis |
|
|
no |
0 |
0 |
yes |
1 |
6 |
grade |
|
|
g1 |
0 |
0 |
g2 |
1 |
0 |
g3 |
2 |
5 |
total score |
0–17 |
0–23 |
10% received an immediate instillation of chemotherapy, a re-TUR was not performed in high-risk patients, and BCG was given without maintenance instillations. Therefore, the predicted recurrence and progression rates of the risk tables might be higher compared to current clinical practice.
Who Needs Adjuvant Therapy
in NMIBC?
The need for adjuvant intravesical instillations depends on the patient’s risk of recurrence and progression to muscle-invasive disease. In patients with a low risk of recurrence and progression, no further adjuvant treatment is recommended following one immediate adjuvant instillation following TURB. In patients with a high risk of progression, that is, those with a high-grade tumor or CIS, further adjuvant treatment with intravesical immunotherapy is recommended.For the remaining intermediate-risk patients, either further intravesical chemotherapy or immunotherapy is recommended.10,28
Intravesical Chemotherapy
Adjuvant intravesical chemotherapy reduces the risk of recurrence with 14–26%, but not the risk of progression or survival.29 There are no differences in efficacy between the available intravesical chemotherapeutic agents whereas side-effects are mostly mild and transient (Table 37.4). Despite the large amount of research on adjuvant
518
Practical Urology: EssEntial PrinciPlEs and PracticE
Table 37.3. Eortc risk tables for nMiBc: probability of recurrence and progression according to total score
Recurrence score |
Prob recurrence 1 year (95% CI) |
Prob recurrence 5 years (95% CI) |
Risk group |
0 |
15% (10–19%) |
31% (24–37%) |
low |
1–4 |
24% (21–26%) |
46% (42–49%) |
intermediate |
5–9 |
38% (35–41%) |
62% (58–65%) |
intermediate |
10–17 |
61% (55–67%) |
78% (73–84%) |
High |
Progression score |
Prob progression 1 year (95% CI) |
Prob progression 5 years (95% CI) |
Risk group |
0 |
0.2% (0–0.7%) |
0.8% (0–1.7%) |
low |
2–6 |
1.0% (0.4–1.6%) |
6% (5–8%) |
intermediate |
7–13 |
5% (4–7%) |
17% (14–20%) |
High |
14–23 |
17% (10–24%) |
45% (35–55%) |
High |
intravesical chemotherapy, the optimal dose, schedule, and duration of treatment have not yet been determined. It seems that long-term instillations, for example, during more than 1 year, only outperform short-term instillations when an immediate postoperative instillation was not administered.35
Intravesical Immunotherapy
Intravesical administration of bacille CalmetteGuérin (BCG), a live attenuated strain of Mycobacterium bovis, causes an inflammatory immunologic response in patients with NMIBC.36 In bladder cancer patients at high risk of tumor recurrence, intravesical BCG instillations reduce recurrence risk significantly (31% reduction compared to MMC). In patients at low risk of recurrence, this effect was not observed.37 In all patients with CIS,Ta,and T1 bladder cancer,BCG instillations reduce the risk of progression to muscle-invasive disease equally (a reduction of 37% in the odds of progression), but only when a form of maintenance instillations has been given.38 Compared to intravesical chemotherapy, BCG induces greater toxicity37 (Table 37.4). Of all patients receiving BCG instillations, approximately 11% have to stop treatment due to mild side effects (irritative bladder symptoms, hematuria) and approximately 5% due to severe side effects (fever, BCG-induced lung infection, liver toxicity, sepsis).32 The optimal dose of BCG has not yet been defined, nor the optimal schedule of
instillations. An induction course of 6 weekly instillations is advised, but the maintenance schedules vary widely. The South-West Oncology Group proposed maintenance schedule of 3 weekly instillations at3,6,12,18,24,35 and 36 months is generally used. BCG is indicated in patients at high risk of progression and is the first-line treatment in patients with CIS. In intermediate-risk patients either BCG or chemotherapy can be administered.10
Immediate Cystectomy and CIS
Cystectomy is the treatment of choice for patients with CIS not responding to adequate BCG treatment.10 The timing of cystectomy remains a challenge and is still controversial. There are no prospective trials comparing immediate cystectomy with BCG, but for some patients immediate cystectomy will be overtreatment.39 Immediate cystectomy after TUR as primary treatment option for CIS patients is advised especially in case of concomitant highgrade papillary tumors.
New Developments: Intravesical
Chemotherapy
Gemcitabine, a chemotherapeutic agent applied systemically for muscle-invasive disease, has been studied for intravesical instillation in patients with NMIBC. The drug is well tolerated
519
BladdEr cancEr
Table 37.4. overview of side effects of the most common used intravesical chemoand immunotherapeutic agents
Intravesical agent |
Side effects |
Incidence |
Recommendations for management |
Epirubicin30 |
chemical cystitis |
13–56% |
consider anticholinergics, if severe postpone |
|
|
|
instillation |
Mitomycin c30,31 |
chemical cystitis |
3–40% |
consider anticholinergics, if severe postpone |
|
|
|
instillation |
|
Eczema-like desquamation of |
4–16% |
careful cleaning of hands/genitalia after |
|
the skin (mainly palms, |
|
voiding (prevention) |
|
soles, perineum, chest, face) |
|
stop further instillations |
|
|
|
|
Bcg30,32-34 |
Local: |
|
|
|
Bcg-induced cystitis |
6–95% |
consider acetaminophen and anticholinergics , |
|
|
|
postpone instillation and consider |
|
|
|
prophylactic ofloxacina |
|
Bacterial cystitis |
26% |
antibiotics, postpone instillation |
|
Urinary frequency |
31% |
consider anticholinergics or prophylactic |
|
|
|
ofloxacina |
|
Macroscopic hematuria |
1–40% |
Postpone instillation until hematuria resolves |
|
contracted bladder |
<1% |
stop further Bcg, hydrodistention |
|
Systemic: |
|
|
|
Fever (³39°c) |
2–17% |
antipyretics, postpone instillation until |
|
|
|
resolution of symptoms consider Bcg dose |
|
|
|
reduction + prophylactic inHb |
|
influenza-like symptoms |
23% |
antipyretics, postpone instillation until |
|
|
|
resolution of symptoms |
|
skin rash and/or joint pain |
0.3–3.3% |
antihistamins and/or nsaids, postpone |
|
|
|
instillation until resolution of symptoms, |
|
|
|
consider Bcg dose reduction + prophylactic |
|
|
|
inHb |
|
Bcg-induced lung infection |
<1% |
Hospitalization, fluids, inHb, rFPc and |
|
|
|
ethambutold for at least 6 months. stop |
|
|
|
further Bcg |
|
liver toxicity |
<1% |
Hospitalization, fluids, inHb, rFPc and |
|
|
|
ethambutold for at least 6 months. stop |
|
|
|
further Bcg |
|
Bcg sepsis |
<1% |
Hospitalization, inHb, rFPc and ethambutold for |
|
|
|
at least 6 months, prednisolone. stop |
|
|
|
further Bcg |
aofloxacin: 200 mg.
binH (isoniazid): 300 mg once daily.
crFP (rifampicin): 600 mg once daily.
dEthambutol: 1,200 mg once daily.