- •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
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180 |
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Practical Urology: EssEntial PrinciPlEs and PracticE |
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Immunotherapy |
(sunitinib and sorafenib), mammalian target |
||
|
|
of rapamycin inhibitors (temsirolimus), and |
|
Until recently, treatment of mRCC has been |
monoclonal antibodies (bevacizumab) appear |
||
based on nephrectomy and limited use of toxic |
to be the most promising agents for treatment |
||
and often ineffective immunotherapy with |
of mRCC. Table 13.3 presents a summary of |
||
interferon-alpha (IFN-a) and interleukin-2 (IL- |
phase III randomized controlled trials of |
||
2). Both are beneficial only for mRCC patients |
targeted therapies in renal cell carcinoma. |
||
with a good performance status and clear cell |
Sunitinib, sorafenib, temsirolimus, and the |
||
subtype histology. IFN-a (alpha) can be used as |
combination bevacizumab with interferon- |
||
comparative control arm for studies investigat- |
alpha are approved for treatment of mRCC.33-37 |
||
ing the efficacy of new drugs for mRCC patients. |
Sunitinib is advised as first-line therapy in |
||
High-dose IL-2 may induce durable complete |
low-and intermediate-risk mRCC patients. |
||
responses in a minority of patients ranging |
Bevacizumab and interferon-alpha can be con- |
||
from 7% to 27%; however, it has more side |
sidered as an additional option for first-line |
||
effects than IFN-a (alpha). Combination of |
therapy in these patients. Temsirolimus should |
||
cytokines, with or without additional chemo- |
be considered as first-line treatment in poor- |
||
therapy, does not improve OS compared with |
risk mRCC patients. Sorafenib has proven effi- |
||
monotherapy.30 |
cacy as second-line therapy for mRCC after |
||
|
|
failure of cytokine therapy. These new agents |
|
Angiogenesis Inhibitor Drugs |
improve quality of life and seem able to stabi- |
||
lize mRCC for a prolonged period of time.30 |
|||
Major advances in the understanding of the |
The mTOR inhibitor everolimus also shows |
||
promising results in patients with mRCC.38 |
|||
molecular biology of RCC have led to the |
Studies are ongoing to compare combination |
||
development of several new therapies that tar- |
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therapies with single agents and to determine |
|||
get ligands at the molecular level, so-called |
|||
the efficacy of single agents as adjuvant ther- |
|||
“targeted therapies”. Figure 13.1 presents the |
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apy after nephrectomy. |
|||
major targets for these targeted therapies. |
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|
|||
Small molecule tyrosine kinase inhibitors |
|
Sunitinib |
PDGF |
Sorafenib |
RAF kinase |
Bevacizumab |
VEGF |
Temsirolimus |
mTOR |
Figure 13.1. targeted drugs with major inhibited targets for treatment of renal cell carcinoma. mtor: mammalian target of rapamycin kinase, Pdgf: platelet-derived growth factor, VEgf: vascular endothelial growth factor.
Conclusion
Angiogenesis inhibitor drugs have an important role in the management of mRCC. However, for a selected group of patients, high-dose IL-2 remains an option. More research and clinical studies are required to identify the optimal combination therapy for patients with mRCC and to define strategies for non-clear cell cancer. Questions regarding optimal sequence and timing of treatment options still need to be addressed.
Testicular Cancer
Testicular cancer is rare and rapidly progressive, but cure rates are almost 100%, regardless of treatment modality. Treatment of patients with testicular cancer is described in the European Germ Cell Cancer Consensus Group (EGCCG) report (part I and II).39,40
Table 13.3. randomized controlled trials of targeted therapies in renal cell carcinoma (from Vakkalanka et al.32) |
|
|
|
|
Study |
Randomization |
No. of |
Objective response |
Progression-free |
|
|
patients |
rate (%) |
survival (months) |
Escudier et al.33 |
Bevacizumab (10 mg/kg) |
|
i.v. every 2 weeks and |
|
ifn-a2a 9 mU s.c.three |
|
times per week |
rini et al.34 |
Bevacizumab (10 mg/kg) |
|
i.v. every 2 weeks and |
|
ifn-a9 mU s.c. three |
|
times per week |
vs. placebo and |
649 |
31 vs. 13 |
10.2 vs. 5.4 (p = 0.0001) |
ifn-a2a9 mU |
|
|
|
s.c.three times per |
|
|
|
week |
|
|
|
vs. ifn-a9 mU |
732 |
25.5 vs. 13.1 |
8.5 vs. 5.2 (p < 0.0001) |
s.c.three times per |
|
(p < 0.0001) |
|
week |
|
|
|
motzer et al.35 |
sunitinib (50 mg)p.o. |
vs. ifn-a9 mU |
|
750 |
31 vs. 6 (p < 0.001) |
11 vs. 5 (p < 0.001) |
|
daily |
s.c.three times per |
|
|
|
|
|
|
week |
|
|
|
|
Escudier et al.36 |
sorafenib (400 mg)p.o. |
vs. placebo |
|
903 |
10 vs. 2 |
5.5 vs. 2.8 (p < 0.01) |
|
twice daily |
|
|
|
|
|
Hudes et al.37 |
temsirolimus (25 mg) i.v. |
vs. ifn-a |
vs. temsirolimus (15 mg) |
626 |
4.8 vs. 8.6 vs. 8.1 |
3.1 vs. 5.5 vs. 4.7 |
|
weekly |
3–18 mU s.c.three |
i.v. weekly and ifn-a |
|
|
|
|
|
times per week |
6 mU s.c.three times |
|
|
|
|
|
|
per week |
|
|
|
IFN interferon, i.v. intravenous, MU million units, p.o. orally, s.c. subcutaneous.
cHEmotHEraPEUtic |
181 |
oncology Urologic for agEnts |
|
|
|