In the last decade, physicians have witnessed a publication will serve as a stimulus to surgeons growing awareness of and concern with diseases of concerned with male reproductive disorders to in the male reproductive tract. Stimulated by this tensify their personal research attempts to develop interest, a refinement and re-evaluation of existing better therapy for diseases referable to the male reproductive system. It is finally hoped that this surgical techniques for treatment of male repro ductive disorders has been concurrently appreci publication will stimulate critical analysis of what ated. Rapid progress in this area has resulted we feel are currently accepted surgical modes of primarily from a cooperative effort from those therapy and to better promote a general inter specialists in the areas of microsurgery, medical change of clinical information referable to these and surgical oncology, endocrinology and neuro disorders. physiology, pathology, immunology, genetics and Those who have provided the text and illustra biochemistry. tions for this volume have contributed a significant As the surgical treatment of diseases and ab amount of work, and we hope that they feel their normalities of the male reproductive system has material has been well used. The editors also wish to expanded, so have the articles describing these often thank Mr."

The past 15 years have witnessed a marked increase in attempts to identify safe and effective treatment alternatives to prostatectomy. This book is a review of the current therapeutic efforts in the management of patients with benign prostatic hyperplasia. It is presented by a group of highly regarded basic and clinical scientists with a major interest in prostatic diseases.
The information provided in this book is aimed at a wide audience including private practice and academic urologists, research fellows and doctors in postgraduate training, and basic scientists interested in prostatic pathology.

One out of every two men over eigthy suffers from carcinoma of the prostate.It is discovered incidentally in many patients with an alleged benign prostatic hyperplasia. In treating patients, the authors make clear that primary radical prostatectomy is preferred over transurethral resection due to the lower complication rate.

Volume XV "Urology in Childhood" was written in 1956/57 and was the first in the series of the Encyclopedia of Urology to appear. This present volume has been constructed as a supplement and the original intention was to deal only with those subjects in which there have been significant advances during the intervening sixteen years. As the work has proceeded, however, it has become evident that there is no aspect of paediatric urology which has not been developed, and no topic which has not been illuminated by many contributions to the literature. Indeed, there has been such a copious flow of publications devoted to children's urinary tract disease that a full review is no longer possible within the compass of a volume of this size: the decision as to what should be left out has therefore been a matter of the greatest difficulty. The choice has been inevit ably arbitrary and many omissions are regretted. The attempt has been made, however, to report the most notable developments of the subject, and perhaps the greatest change in the practice of paediatric urology has been the full integra tion with paediatric nephrology. The team approach to infant disease in particular has led to greatly improved results. I have been fortunate to have Dr. T. M."

How to treat advanced prostatic cancer remains controversial, despite intense basic and clinical research investigating the pathogenesis and natural history of this unique cancer highly prevalent in elderly males. Nine experts were asked to meet and discuss the facts. This resulting monograph gives an overview of the available knowledge on all aspects of the subject. The objective evaluation and consensus opinion of the authors presented here set this book apart from other publications with conflicting viewpoints. For readers eager to obtain a comprehensive and balanced view of the thousands of clinical contributions and clear advice on the choices, this book is a must.

Stone in the urinary tract has fascinated the medical profession from the earliest times and has played an important part in the development of surgery. The earliest major planned operations were for the removal of vesical calculus; renal and ureteric calculi provided the first stimulus for the radiological investigation of the viscera, and the biochemical investigation of the causes of calculus formation has been the training ground for surgeons interested in metabolic disorders. It is therefore no surprise that stone has been the subject of a number of monographs by eminent urologists, but the rapid development of knowledge has made it possible for each one of these authors to produce something new. There is still a technical challenge to the surgeon in the removal of renal calculi, and on this topic we are always glad to have the advice of a master craftsman; but inevitably much of the interest centres on the elucidation of the causes of stone formation and its prevention. Professor Pyrah has had a long and wide experience of the surgery of calculous disease and gives us in this volume something of the wisdom that he has gained thereby, but he has also been a pioneer in the setting up of a research department largely concerned with the investigation of this complex group of disorders, so that he is able to present in terms readily intelligible to the general medical reader the results of extensive biochemical investigation in this area.

The book provides a comprehensive uptodate review of the present state of knowledge of urinary enzymes. Since it deals with all the essential questions currently being discussed in connection with urinary enzymes, it will be of interest to biochemists, clinical chemists, renal physiologists, nephrologists and clinicians working on renal problems.The chapters are grouped into 5 parts, the first offeringan update of the biochemical and morphological fundamentals of the excretionof urinary enzymes, including a description of the distribution of diagnostically relevant enzymes along the nephron, the mechanisms of enzyme release, and the physiological factors influencing the excretion rate. The chapters in the second part deal with the methodological fundamentals ofthe activity determination of urinary enzymes (preanalytical treatment, quality assurance, methodical details for the most important enzymes, reviewon reference intervals). The four chapters in the third part review aspects of urinary enzyme excretion in clinical medicine (renal, renal associated, and urological disorders, kidney transplantation, nephrotoxicity, extrarenal diseases) and includes a special chapter on the general background for interpreting data on urinary enzyme excretion. The fourth part, consisting of 3 chapters, covers urinary enzymes in animal experiments (animal models, influence of different substances on urinary enzyme excretion, reference values in various animals). The book concludes with a review of the posibilities for using renal enzymes as the basis for alternative methods of screening toxic substances.

The first symposium of the working group on experimental urology of the German Society of Urology was held in Cologne in 1972. It was meant to be a platform to present and, in particular, to discuss experimental studies developing new diagnostic and therapeutic approaches, and to promote in novation in urology in Germany. This plan was well received, and during the last 16 years both the number of participants from other European and overseas countries and the number and quality of presentations have been continuously increasing. At the most recent meeting, held in Aachen in 1988, new data were presented on renal cell cancer, andrology, prostatic cancer and adenoma, bladder cancer, urinary diversion, urodynamics, renal pathophysiology, transplantation and the pathogenesis and treatment of urolithiasis. The present book contains 44 of the 109 papers given at the Aachen meeting, covering both basic and clinical research. It will be of eminent interest to all scientifically minded urologists, oncologists, neurophysiolo gists, endocrinologists, and pathologists because it is a synopsis of all the major scientific research currently being conducted in urology in Europe. There are no other books available which offer as comprehensive a cover age of recent experimental issues in urology. The aim of the series Inves tigative Urology is to demonstrate the continuous development of research in urology and to encourage all colleagues interested in experimental urol ogy to continue their important activities and create new international co operation.

The purpose of this book is to provide some basic information regarding the fundamentals of magnetic resonance (MR) for all those who are less familiar with the technique and interested in MR spectroscopy and its possible applications in research and clinical practice. It will stimulate the reader to look more closely at the various topics covered by the contributors to this volume: tumor cell metabolism, kidney function, organ viability. Finally, several applications of high-field spectroscopy and imaging are illustrated. The book focusses on proven and possible clinical applications of MR in nephrourology: renal cell carcinoma, metabolic investigation of the kidney and pretransplant assessment of organ viability. The examples are thoroughly discussed and abundantly illustrated. The reader will benefit from this book by receiving a review of research and clinical aspects of MR simultaneously.

The aimoftheHypospadiasand Genital Symposium, held at theUniversityof California,SanFrancisco,wastoprovideaforumforauthoritativeinvestigatorswhoare activelyinvolvedinthevariousdisciplineswhichdefinetheleadingedgesofhypospadias and genital research. It is important for such investigators to continue to meet for the purpose of discussing the latest developments in their individual fields, to analyze the significanceofcurrent research, to discuss new tactics for unresolved problems and to develop new theories andapproaches asneeded. The two day conference on hypospadiasandgenitaldevelopment research was organizedintothreesections: 1)HumanStudies;2)MechanismofGenitalDevelopment; and 3) Endocrine Disruptors and Sexual Dimorphism in the Animal Kingdom. Each sessionwasintroducedbyanexpertmoderatorfollowedtheinvitedspeakerswithtimefor extensiveinteractionbetweeninvestigators. Thisbookdocumentstheproceedingsofthe HypospadiasandGenitalDevelopmentSymposium. Iwould especially like to thank Kari Gaudette for editorial assistants, Cynthia Ashe, Selcuk Yucel, Antonio Souza and the administrative staffinthe Departmentof Urology. Ihopeyoufindthisresourceuseful. Laurence S. Baskin,M. D. ProgramChair ChiefPediatricUrology UCSF vii ACKNOWLEDGEMENTS Supportforthissymposiumisgratefullyacknowledged TheNationalInstituteofHealthGrant#R13DK*HDS997 UCSFDepartmentofUrology AmericanUrologicAssociation CONTENTS Introduction...1 SECTIONI. HUMANSTUDIES EpidemiologyofHypospadias...*...*...25 J. DavidErickson EndocrineEvaluationofHypospadias...31 G. HyunandT. Kolon EndocrineAbnormalitiesinBoyswithHypospadias...45 R. I. Silver GeneticandClinicalStudiesonHypospadias...***...**...*...73 A. Nordenskjold SECTIONII. MECHANISMOFGENITALDEVELOPMENT DevelopmentofthePenileUrethra. . 87 G. CunhaandL. Baskin AnatomicalStudiesoftheMouseGenitalTubercle...103 L. Baskin,W. Liu,J. Bastacky,andS. Yucel AnatomicalStudiesoftheFibroblastGrowthFactor-l0Mutant,Sonic HedgeHogMutant,andAndrogenReceptorMutantMouseGenital Tubercle...*. **. . 123 S. Yllcel,W. Liu,DCordero,A. Donjacour,G. Cunha,andL. Baskin DevelopmentalGeneticsofHypospadias...149 M. Cohn xiii xiv Contents DevelopmentoftheMouseExternalGenitalia: UniqueModelof Organogenesis...159 K. Suzuki, K. Shiota,Y. Zhang,L. Lei,andG. Yamada NewConceptsontheDevelopmentoCtheVagina...173 E. Shapiro. H. Huang,andX. R. Wu SECTIONIII. ENDOCRINEDISRUPTORSANDSEXUAL DIMORPHISMINTHEANIMALKINGDOM EndocrineDisruptionOverview: AreMalesatRisk? 189 T. Colburn EndocrineDisruptionandHypospadias...203 G. Steinhardt Toxicant-InducedHypospadiasintheMaleRat * 217 L. E. Gray. . I. Ostby,J. Fun,C. Wolf,C. Lambright,V. Wilson, and N. Noreiga MasculinizationofFemaleMammals: LessonsfromNature...243 N. J. PI:H'candS. Glickman Index...255 SectionI Introduction HYPOSPADIAS LaurenceS. Baskin* M. D. ,FAAP 1.

Androgen Receptors is the most comprehensive and up to date volume on the topic, including discussions of the basic mechanisms of androgen-androgen receptor actions, their roles in the androgen-related diseases, and their potential clinical applications. Key topics covered include: -The discovery and cloning of the androgen receptor; -Androgen receptor coregulators; -Androgen related genes and their consensus DNA response elements; -Basic mechanism of action including functional analyses, cellular localization and phosphorylation studies; -Cross-talk to other signal transduction systems; -The recent connections of androgens to women's diseases, such as osteoporosis and ovarian cancer. This book is of interest to students, basic scientists, and clinicians as both a study guide and reference of research in the androgen field. It could also be used as an advanced level text in endocrinology, urology, OBGYN, or oncology.

The aim of Bladder Research Congress, San Francisco, California, April 23-25, 1998, was to provide a forum for authoritative investigators who are actively involved in the various disciplines which define the leading edges of bladder research. It is important for such investigators to continue to meet regularly for the purpose of discussing the latest developments in their individual fields, to analyze the significance of current research, to discuss new tactics for unresolved problems, to critically evaluate current theories, and to develop new theories and approaches as needed. The two and a half day meeting was organized into five half day sessions, with each session encompassing one of five topics: (1) Epithelial-Mesenchymal Interactions; (2) Ex tracellular Matrix and Muscle; (3) Nerves and Pharmacology; (4) Infection and Immunol ogy; and (5) Oncology. Each session was introduced by a moderator followed by five to six invited expert speakers with time for extensive interaction from the participants. Two late-afternoon poster sessions allowed further interactions between investigators. This book documents the proceedings of the Bladder Research Congress. It is organ ized into the five half-day sessions of the meeting with moderators overview and an edited transcription of discussions that followed each presentation. I would like to thank Sarah Burke and the Office of Continuing Medical Education, USCF; Joanne Hayward, Editorial Assistant; and Miriam Escamilla, Administrative Assis tant. I hope you find this resource useful. Laurence S. Baskin, M.D.

The management of advanced renal cell carcinoma is still problematic. Surgery, although the therapy of choice for locally advanced renal tumors, is still controversial as the treatment for metastases. The role of surgery in the management of patients with pulmonary, bony, and liver metastasis is one of the subject matters discussed in this book. Our results with series of patients undergoing resection of metastases from the lung, bone, and liver show that surgery may be appropriate in selected patients with a good performance status, although most of them certainly cannot be cured by this procedure alone, i.e., in the absence of effective adjuvant therapies. As recent developments show, new strategies for immunotherapy of renal cell carcinoma represent a modest advance over traditional approaches in the treatment of this cancer, such as chemo- and radiotherapy. Clinical trials employing recombinant interferon-a and interleukin 2 produced response rates in up to 30% of patients treated, as evidenced by the European Immunotherapy Trials Program. The adverse reactions and the lack of efficacy in the majority of patients warrants the search for new immunotherapeutic approaches.

The use oflasers in clinical practice is increasing rapidly, both in the definitive treatment of disease and in the palliation of symp toms. Consequently, this sixth contribution to the Bloomsbury Series in Clinical Science is particularly timely. It opens with an introduction to the basic physics of lasers and then focuses on the current use of lasers in urological practice, and concludes by reflecting on their potential for the future. Edited, and with several contributions by Tom McNicholas, the book also contains contributions from a number of workers at the National Medical Laser Centre in University College Hos pital. London. Given their ever widening application, there can be little doubt that lasers will be a subject the series will return to again. To date, the series has been concerned with a wide range of topics of fundamental importance in clinical science. It has now gained momentum and future titles continue to reflect its wide sphere of interest. As Series Editor, I would welcome suggestions from readers of topics and issues that could usefully be addressed in the series.

This book is the record of the proceedings of a NATO Advanced Study Institute held in Erice, Sicily, from the 2nd - 12th June 1981, during which scientists and clinicians interested in the problems presented by cancer of the kidney and the prostate were encouraged to present, to discuss and to challenge the opinions expressed and the beliefs held by the different contributors. It is uncommon for scientist, physician, and surgeon to meet with great regularity or for prolonged periods of time and it must be exceedingly rare for such people to immerse themselves in each other's work and company for aperiod of almost two weeks. For this to occur in a situation of total isolation such as that provided by the marvellous Ettore Majorana Centre in Erice, Sicily must be unique. The fact that differences of opinion remain will be evident to all who read the book, as will the wealth of scientific and clinical work being undertaken within and beyond the NATO countries. We are very much indebted to the Science Committee of NATO for their recommendation for support for this meeting and to the Ente Fiuggi and to several pharmaceutical firms.

The introduction of lasers into operative medicine and advances in fiberoptic technology have made a significant contribution to minimally invasive surgery. This book was written to raise awareness of the capabilities and advant ages of lasers in urological surgery and to make this tech nology more widely accessible. The book reflects the cumulative experience of 25 years of laser research and clinical application, starting in 1972 with studies on laser tissue interactions, endoscopic studies with fiberoptic "sutures;' and the first clinical use of lasers in 1975 and 1976. These early efforts were followed by the develop ment oflaser lithotripsy in the early 1980 s and a Lubeck based research program leading to the development of a "smart" laser lithotriptor (Lithognost) in the late 1980s. There have been recent advances in the field of photo dynamic diagnosis based on the use of locally adminis tered photo sensitizers, a development that will redefine the role of the Nd:YAG laser in the treatment of bladder cancer. Perhaps the most interesting concept is the inter stitiallaser therapy of prostatic hyperplasia and, perhaps one day, certain forms of prostatic cancer. We have also developed a technique, first described in 1986, for the laser treatment of schistosomal bladder lesions. I dedicate this book to the many pioneers oflaser medi cine and to all the colleagues and research assistants who accompanied me on this journey. I cannot name them all; their names can be found in more than 300 publications.

The aim of this series is to bring the reader up-to-date data and opinions on the practice of urological surgery. The ten titles published since 1982 have all been concerned with adult urology, with reference to paediatric problems included in some relevant chapters. The addition of this title on paediatric urology is especially welcome because it brings together the important components of the sub-specialty. This book has developed from one of the first of the annual courses in urological sub-specialties provided for trainees in the UK as part of their higher surgical training. But that audience is not the only one at which this book is aimed. In his Preface, Robert Whitaker emphasises the changes over the past ten to fifteen years: this means that any urologist over the age of 45 is already out of date in much of his or her knowledge of paediatric urology - unless there has been a genuine attempt at continuing medical education. Attendance and discussions at meetings and reading of current literature are useful methods of updating our knowledge. However, this book provides a much-needed link with the paediatric urology course and is a splendid reference source for all urologists. Robert Whitaker has gathered together four eminent co-authors to present their material on the main issues in paediatric urology. In keeping with the aims of this series, the data are up to date, the perspectives are contemporary and in every way this is an excellent addition to Clinical Practice in Urology.

The anticipation of seeing and having to manage patients suffering from sensory disorders of the urinary tract brings dismay and foreboding to the urologist. This stems from his experience of the time that these patients take up, both at the stage of initial interview and subsequently during numerous consultations over periods of months and years. This and the largely unsatisfactory response to various forms of therapy in the past are reason enough for this bold attempt to define with objectivity the notoriously subjective disorders of interstitial cystitis, urethral syndrome and prostatodynia. In writing this book the principal aim of the authors has been to define these three entities concisely and to describe the investiga tional methods which are required to establish the diagnosis in each case. The importance of this cannot be overestimated since, when the label of one or other of these conditions is attached to a patient, further objective consideration of the case is-endangered. The casual attribution of these sensory diagnoses to inappropriate cases is already on record as having dulled clinical awareness and led to oversight of progressive disease and its sometimes avoidable conse quences."

The handbook on lithiasis edited by Kurt Boshamer and originally brought out in 1961 was for more than two decades the standard work in this field for researchers and clinicians alike. However, our knowl edge of urolithiasis has been increased so enormously - by worldwide interdisciplinary research into the genesis of urinary calculi, by the new treatment possibilities opened up principally by advances in tech nology, and by the success achieved in prevention of recurrence - that it is almost impossible to take in all the relevant journal articles, books chapters, monographs, and proceedings. It was therefore our aim in this, the first of two independent vol umes, to provide a concise but comprehensive summary of current knowledge concerning the morphology and composition of calculi, epidemiology, pathogenesis, and diagnostic techniques. The most re cent developments are described, and nothing in the world literature is ignored. A second volume will cover medical therapy, operative, in strumental and noninvasive treatment, and prophylaxis. To have any chance of success, treatment and prophylaxis must be based on knowledge of calculus formation. Study of the composition of calculi has yielded important information regarding the conditions for formation, and this underlines once again the great value of analy sis of urinary concretions. Evaluation of epidemiological data has im portant consequences for the individual patient."

Prostatitis continues to be a major clinical enigma. In this book, all modern aspects of etiology, pathogenesis, diagnosis and therapy are critically evaluated. Of special interest to the readers will be the modern diagnostic management of chronic prostatitis and the debatable therapeutic approach to chronic nonbacterial prostatitis. From the contents: Radical Transurethral Prostatectomy for Chronic Bacterial Prostatitis; Etiology, Pathogenesis, and Inflammatory Reactions in Chronic Bacterial Prostatitis; Therapy of Nonbacterial Prostatitis; Ultrasonographic Features of Prostatitis.

Obstetric fistula is as old as mankind. While the incidence has diminished progressively with better health care in Western societies, the situation has changed little in many developing countries. Fistulae of pelvic organs, often monstrous defects, still are a major complication of child-birth causing misery to uncounted young women, and if they cannot find help in one of the very few hospitals with trained specialists, they became urological cripples losing everything: family, home and job. The magnitude of the problem is illustrated by some figures given by Reginald and Catherine Hamlin-about 700 fistula patients treated each year-a total of over 10,000 cases operated upon in their fistula hospital in Addis Ababa, Ethio pia. Most of these injuries could be prevented by better health care at the village level as some studies have shown conclusively. The incidence of fistula is an indicator of the standard of health and obstetrical care. The author of this book-Obstetric Fistula-is an internationally known Australian gynaecologist who for many years has been interested in all aspects of gynaecological urology, especially urinary stress inconti nence, other forms of involuntary loss of urine, and associated gynaeco logical conditions. He has devised a number of new operations to treat pelvic defects. Robert Zacharin's interest in obstetric fistula was a con sequence of his surgical activity in developing countries."

These proceedings emanate from the Second Prouts Neck Conference on prostate cancer held on October 17-19, 1986, the theme of which was treat ment, with focus on current issues and future research that is needed to answer critical questions related to optimal management of the various stages of prostate cancer. The objective was to reveal the most crucial problems impeding progress and to crystallize the combined multidisci plinary input generated by the conference into focused concepts or recommendations for presentation to the National Cancer Institute (NCI), with the ultimate intent of targeting research to address the priority issues identified. In organizing the workshop, every effort was made to maintain a multidisciplinary balance among nationally renowned authorities on prostate cancer. Thus, leading surgeons, radiation and medical onco logists and biostatisticians were in equal presence. While there were spirited exchanges with careful scrutiny and critique of all data pre sented, there was a common belief that the challenge of prostate cancer would be best approached in this multidisciplinary Organ Systems-oriented fashion. During the course of the conference, it became apparent to all present that major nomenclature and procedural barriers have made it generally difficult, and frequently impossible, to compare results of clinical research."

Tumours in Urology is an up-to-date review of the advances in clinical management, clinical science, and basic science aspects of urological oncology. The text is divided into four parts for ease of reference: In these sections the molecular biology and biochemistry of bladder cancer, prostate cancer, and renal cell cancer are examined. There are authoritative reviews of the risk factors in superficial bladder cancer, the role of chemotherapy and bladder reconstruction in invasive cancer, along with comparative views of conservative treatment and the role of radical surgery in prostate cancer. Current methods of hormonal manipulation are also discussed. Conservative surgery for renal cancer, the use of interleukins, and the use of radical lymphadenectomy for testis cancer are comprehensively set out for the reader. A unique feature is the review at the beginning of each section of the controversial areas within each major topic. This gives the reader an excellent overview of recent advances in the field.

The most recent experimental work in urology is presented in this volume. Itcontinues the biennial publication of the reports given at the internationalsymposia for experimental urological research; the tenth symposium was held in Munich in June, 1990. The wide range of subjects covers renal cell cancer and adenoma, bladder cancer, urinary diversion, uro- dynamics, renal pathophysiology and transplantation as well as the pathogenesis and treatment of urolithiasis.

The first edition of "Testosterone: Action, Deficiency, Substitu tion" was published in 1990. Since then our understanding of the hormone that turns males into men has tremendously increased. Therefore, the editors felt that a second extended edition of the book is warranted in order to summarize established and recent findings in the field and to present the reader with an up-to-date is reflected by the textbook. The increased mass of knowledge growth of the volume from 14 to 20 chapters. In the updated edition the biochemistry and metabolism of androgens have been complemented by extensive information on the molecular biology of the androgen receptor and its disorders. The key role of testosterone in spermatogenesis is now better de fined. We have a more complete understanding of the psychotro pic effects of testosterone and know so much about the different target organs and functions that individual chapters deal with testosterone and the prostate, lipids and the cardiovascular sys tem, hair, bones and muscles. The general chapter on pharmacol ogy and clinical uses of testosterone, in particular in male hypo gonadism, is extended by pharmacokinetic studies on testoster one preparations and individual substitution modalities using testosterone esters as well as implants and advanced trans dermal applications. The physiologic basis and possible clinical applica tions of testosterone in non-gonadal diseases, in male senes cence, in hormonal male contraception and in transsexuals are discussed. The last chapter describes the role of "investigative" steroid biochemistry applied to tracking anabolic steroid abuse."