A vast number of children in the United States are evaluated and treated for urologic conditions by urologists practicing general urology due to the relatively few fellowship-trained pediatric urologists. Pediatric Urology: A General Urologist's Guide is written specifically for general urologists as a concise and comprehensive reference of the more common pediatric urologic conditions. Other health practitioners (i.e. pediatrician, family practitioner, residents, medical students, and mid-level providers) will also find this book a key reference. Written by well-respected pediatric urologists, this volume will assist the health care provider to rapidly review the essential aspects of the physical examination, evaluation, diagnostic testing, and management while the patient is still in the office. The chapters are arranged into four sections to allow for easier access to the information: office urology, genitalia, urinary tract, and miscellaneous topics. Furthermore, the first chapter of the book will be dedicated to facts and figures (ex. normal penile and renal lengths based on age, dosing of common medications, and grading system for vesicoureteral reflux) that serves as a single source for this information. Pediatric Urology: A General Urologist's Guide offers the reader the essential information to assist them in the care of children.

Prostate cancer remains the most common malignant tumor in elderly men. The National Cancer Institute estimated 210,000 new cases of prostate cancer in 1997. There is, however, no means of documenting the true incidence of prostate cancer because of the difficulty in detecting all cases. Even using yearly rectal exams, PSA determinations, and ultrasound-guided prostate biopsies, many cases are missed. Suffice it to say that prostate cancer is a widely occurring disease in men and early detection and treatment are extremely important. When I trained in Urology under Dr. Reed Nesbit at the University of Michigan from 1956 to 1959, the diagnosis of prostate cancer was made by a rectal examination and an acid phosphatase determination. If there was a small nodule in the prostate, then an anterior-posterior X-ray of the pelvis was obtained to look for possible bony metastases. If the acid phosphatase was normal and there was no evidence ofa bony metastasis, the prostate was exposed through the perineal approach and a biopsy of the nodule was obtained and sent for frozen section to Pathology to determine if it was indeed a cancer of the prostate. If the biopsy came back positive, the surgeon then proceeded to do a radical perineal prostatectomy. In those days, we usually did eight to ten radical perineal prostatectomies yearly. Many times the nodule that was biopsied was benign, and the incision was simply closed.

The first International Symposium on Urolithiasis Research was held in Leeds, England, in 1968. The meeting was the first in what was to become a series of symposia intended to gather together a diverse group of biochemists and physicians, urologists and engineers, with a common interest in factors affecting the formation of human urinary stones. Since its inception the series has threaded a peripatetic course back and forth across the Atlantic Ocean, from Madrid in Spain, to Davos in Switzerland, to Williamsburg in the USA, to Garmisch-Partenkirchen in Germany and Vancouver in Canada, under the guardianship of Drs Nordin, Cifuentes Delatte, Fleisch, Smith, Schwille, Dirks and Sutton, and their colleagues. In 1992, for the first time, the meeting moved to the southern hemisphere, to Cairns in Northeastern Australia. Unlike most previous symposia, there were no invited papers. Instead, the submitted abstracts were allowed to dictate the content of the meeting so that the conference programme would reflect the flavour of current research in the field. To achieve this, all abstracts were graded anonymously by three referees to determine their categorization as oral, theme poster, or general poster presentations. The 300 or so accepted absracts were then allocated to seven plenary sessions, nine theme poster discus sion groups and three large general poster sessions."

An analysis of all the current avenues of treatment with emphasis on multidisciplinary considerations. Select international authorities present in-depth coverage of their areas of expertise, each topic covering the background, anatomy, physiology, diagnosis, classification, and treatment. Part I focuses on the study of male infertility and includes discussions of the basic sciences, office evaluation, laboratory and imaging techniques, and the use of testicular biopsy. This is followed by specialised chapters dealing with immunologic infertility, genital inflammation, reactive oxygen species, medical management, sperm processing and preventive adolescent andrology. Part II reflects a more diverse format in the coverage of sexual dysfunction and includes discussions of androgen insufficiency, nocturnal penile tumescence studies, neurotransmission, penile neurology, premature ejaculation, psychogenic impotence and the latest medical, non-invasive and surgical treatments.

These proceedings of the 5th Prouts Neck Meeting on Prostate Cancer, held in October, 1989, highlight the many advances in the understanding of prostatic growth and function at the cellular and molecular levels which have been registered since the first Prouts Neck Meeting in 1985, a meeting which also focused on the then current concepts and basic approaches to understanding prostate cancer. Inter vening Prouts Neck Meetings in 1986, 1987 and 1988 were devoted to treatment, image cytometry and clinical markers. As before, the Prouts Neck tradition of bringing together an international, multidiscipli nary group of experts for 3 days to exchange ideas and new data, in the relaxed atmosphere of an old iun on the scenic Maine coast, proved to be an ideal combination for a highly successful conference. Accordingly, the Organ System Program of the National Cancer Institute plans to use the Prouts Neck model for future conferences on other solid tumors (bladder in 1990 and kidney in 1991) and will return to the prostate in 1992. A new dimension was added to the current program through the inclusion of a poster session to recognize the research of pre-and postdoctoral investigators. The posters were judged by Drs. Collette Freeman, Frank French, Shutsung Liao, Robert Matusik and Henry Sun. The three winners, in alphabeti cal order, were John Fabian, Robert Getzenberg and Ming Fong-Lin."

Since the late 1960s, there has been an acceleration of research focused on understanding how the efferent ducts, the epididymis, and the vas deferens function with respect to the maturation and storage of spermatozoa and as hormone dependent tissues. Another major interest in the epididymis is that it is an attractive target for the development of male contraceptives. There are well over 16,000 peer reviewed articles in the literature on these tissues, their structure, gene expression, protein synthesis and function. Regular international meetings have been initiated that are dedicated to this field. Thus, there is an urgent need for a comprehensive reference volume that spans every facet of epididymal biology, from historical background to the most current results, from basic cell and molecular biology to clinical issues. Well-established experts from every part of the world have contributed to this volume. By necessity, each author was given page limitations so that many topics are not dealt with exhaustively. Whenever possible, references to more comprehensive discussion of specific topics are included.

"Fertility Preservation in Males: Emerging Technologies and Clinical Applications" contains a selection of the valuable chapters and protocols of Seli and Agarwal s previously published hardcover text "Fertility Preservation: Emerging Technologies and Clinical Applications." Newly available in this convenient and affordable softcover format, this practical reference guide provides an update on options for fertility preservation in men, while also discussing important related epidemiologic, ethical, medico-legal, psychological, and social aspects. Using a format that combines concise scientific background with practical methodological information and easy-to-grasp algorithms, the chapters all conform to a uniform structure, including step by step protocol of laboratory procedures, key issues in commentary and a list of references. The result is a unique resource for reproductive endocrinologists, urologists, embryologists, reproductive scientists, and oncologists."

The master tool of logic is the syllogism. If A> Band B> C, then it must follow as the night the day that A > C. If the major and minor premises are true or scientifically correct by current knowledge, the conclusion is true or at least scientifically correct by current knowledge. The demographer of today beams a clear message, which if not true is at least scientifically correct by current knowledge. In the first 80 years of the Twentieth Century, the 'over-65' population of Americans increased eight fold. By century's end it will have increased 12-fold and shortly thereafter will include one in five Americans. While initially a fact of the developed world, the pace of similar graying is accelerating even more rapidly in the Second and Third Worlds. This gray delta constitutes about 35 million living Americans, who may use one-half or more of the health care resources. A would have to be a lot more foolish than B if they failed to recognize that in the coming decade the causation, case-mix, and area of the gray delta demands a change from early, mid-or even later-century medicine. If Homer Smith was right in saying, "We are what we are because we have the kind of kidneys we have" and "The kidneys make the stuff of philosophy", then the who, what, where, when, and why the gray delta will be cared for must focus on the stuff of geriatric nephrology.

This drug is a landmark discovery, which consequently has become the definitive therapy for the treatment of erectile dysfunction (ED). Following the major breakthrough in the field of nitric oxide (NO)-physiology and pharmacology leading to sildenafil being marketed, the most current information is presented in this reference book, including ongoing research from several disparate groups about NO as endothelium-derived relaxing factor (EDRF) and also as a neurotransmitter for nerves innervating erectile tissue in mammals.

The development of sildenafil as an oral phosphodiesterase-5 (PDE5) inhibitor drug for the treatment of ED resulted in one of the first products, which made its way successfully from basic NO research to routine clinical therapy.

This volume addresses all fields of sildenafil application in both men and women. In a highly competitive research environment with a critical medical need for drug improvements the reader will learn more about clinical resistance to sildenafil treatment and the modalities to overcome the failure rates.

The individual chapters cover clinical use, pharmacokinetics, pharmacodynamics, biochemistry, and cultural aspects. They are written by leading experts in their respective fields. Therefore, readers whether professionals in the pharmaceutical industry, physicians treating ED, biochemists, chemists or pharmacologists will find a detailed and up-to-date knowledge base about current research activities and an excellent overview for further research on this compound class and its cultural impact."

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 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 last twenty years has seen the biggest revolution in the treatment of renal tract stone that has ever been experienced in the history of urolithiasis. The treatment of upper tract renal stone has progressed from the days of a very traumatic and morbid procedure to the relatively innocuous, walk in/walk out therapy of extracorporeal lithotripsy. This progression of events has resulted in a complete reappraisal of management of all types of urinary calculi. From an initial reluctance to treat many stones because of the trauma involved, we have now passed to a situation where smaller and asympto matic stones may be pre-emptively treated before the treatment of serious clinical problems. It is true to say that in Westemized societies the problem of urolithiasis has almost completely been solved by the advent of advanced technology. In this volume, attention is drawn to the fact that there are still persistent difficulties in treating urolithiasis in the less developed and less affluent societies. The differences in epidemiology of urolithiasis in various areas of the world are highlighted, noting a rapid decrease in the incidence of bladder calculi in impover ished areas where affluence increases. Coupled with this progression of affluence however is the well documented increase in the incidence of upper tract renal stones of oxalate nature. This scenario has been almost universal across all coun tries in the last few decades.

Because of many advances in medicine and biotechnology, an increasing number of individuals are surviving into old age, and we are now challenged to apply sophisticated medical knowledge to the care of the elderly citizen. In nephrology, individuals older than 65 are the fastest-growing group of patients requiring dialysis. Similarly, in increasing numbers, elderly persons present themselves with renal complaints to their family doctor, the geriatrician or the nephrologist. In August 1998, with the financial support of the John A. Hartford Foundation, leaders in geriatrics, nephrology and urology met in Jasper, Alberta, for one week to discuss their areas of special knowledge and to learn from each other. Geriatricians learned from nephrologists, nephrologists learned from geriatricians, and both came to see that they had much in common. All participants discovered a common interest, challenge and commitment, namely, to provide the best renal care to a progressively aging population and to teach their fellows the principles of the other collaborating specialties. This book contains all the papers presented at this meeting and also the text of group discussions on Training and Education, Special Clinical Problems in Geriatric Patients, and Recommendations in Basic and Clinical Research. Nephrology and Geriatrics Integrated will prove useful to both nephrologists and geriatricians in their efforts to manage the renal complaints of the elderly, who come to them in increasing numbers.

In 1963 Professor Huggins! wrote "more than one half of the male population over the age of 50 suffer from benign tumors known as prostatic hypertrophy. Often an enlarged prostate is the only difficulty to cloud an otherwise tranquil old age". This statement emphasizes two important features of benign prostatic hypertrophy (BPH); the frequency with which it occurs and its association with increasing age. The true incidence is difficult to determine as most data relate to selected groups of patients; moreover, the diagnostic criteria of prostatic hypertrophy are not clearly defined. Normality merges imperceptibly into abnormality, for even in men who are clinically normal, rates of urinary flow decrease with 2 increasing age . Despite these inaccuracies, incidence figures show the magnitude of the problem; Flocks (1963) 3 reported that 65% of American men over 60 years suffer from it and in a selected group of Danish men 43% had symptoms of the 4 disease ; similar figures are reported for the U ni ted Kingdom 5. At present most patients with BPH, who need treatment, undergo surgical prostatectomy which may be considered the usual treatment. The frequency of the disease alone, creates certain problems, for annually more than 30000 men are admitted to hospital in the United States with this as a primary diagnosis and with an ageing population the figures can be expected to increase.

The basic principles of the phenomenon "erection" have been known since the pioneering work of Kolliker, Eckhard and Langley in the nineteenth century. Nonetheless, under the influence of Freud, erectile dysfunction was predominantly at tributed to psychogenic factors. A more liberal perception of sexuality since the 1960s, the development of new and refined diagnostic techniques, and the expansion of basic research activity resulted in a new concept of erectile dysfunction, identifying arteriogenic, venogenic, endocrinologic or myopathic (cavernous smooth muscle dysfunction) factors. From this research other considerations such as autonomic innervation, cavernous endo thelial intactness or impaired neurotransmitter pool are being introduced into routine clinical assessment. A reevaluation of psychogenic etiology with a consequential new concept of psy chogenic impotence is on the rise. In this book the new concepts of basic knowledge on cavernous smooth muscle function and its supraspinal, spinal, and local control; the new diagnostic approaches in psychogenic and autonomic factors; and the new developments of reconstructive therapeutic options for the patient have been tied together. Outstanding and internationally renowned experts in the field of erectile dysfunction have given detailed insight into the latest basic and clinical developments. Well-established diagnostic and thera peutic techniques are presented by experienced colleagues. We hope that this book will help the reader to get an overview of the current concepts of erection. Furthermore, we hope that international collaboration in basic and clinical research in the field of erectile dysfunction will render an update necessary in the near future.

This book represents the proceedings from a conference that took place in Dallas in the spring of 1999 which was entitled "Pediatric Gender Assignment - A Critical Reappraisal". Some participants rightfully argued that the conference really focused on the issue of pediatric gender assignment, and that reassignment was not applied in most cases. Their comments were reflected in the title of this monograph. This multidisciplinary meeting was sponsored by a conference grant from the National Institutes of Health, and a broad inquiry into this complex topic took place from many points of view. Basic scientists offered insight into mechanisms of sexual differentiation of the gonads, physical phenotype and imprinting of the central nervous system. Endocrinologists reviewed their experience in diagnosis and management, surgeons described traditional as well as innovative approaches, and there was strong representation from the ethical and behavioral sciences. In putting together such a panel, it was essential that we identify a cast of speakers who could address their viewpoints with strong convictions, and yet not let their passions render the meeting counter productive. We were not disappointed. While many differing points of view were firmly expressed by the panelists and audience, all viewpoints were accorded the respect they deserved. The concept behind the meeting and this book really originated in 1997 shortly after Diamond and Sigmundson published their long term follow up study of the John/Joan case.

The 6th triennial meeting of the International Study Group for Tryp- tophan Research (ISTRY) was held May 9-12, 1989 in Baltimore, Maryland (USA). From the wide variety of topics and disciplines represented, as documented in this volume, it is clear that tryptophan research and ISTRY are alive and well. ISTRY traces its or1g1ns to at a tryptophan symposium organized in 1971 by H. Schievelbein at Hohenried near Munich (Germany). Up to that time there had been occasional international tryptophan conferences at irregular inter- vals. A number of participants at the Hohenried meeting felt that an inter- national tryptophan organization should be formed to organize regular meet- ings and to foster collaboration and information exchange on tryptophan-re- lated topics. Thanks mainly to the founding work of H. Schievelbein and W. Kochen, an executive committee was elected and ISTRY was born. The inaugural meeting in 1974 was held in Padova (Italy) to honor L. Musajo, one of the foremost pioneers in tryptophan studies. This first ISTRY meeting was suc- cessfully organized by L. Musajo, G. Allegri, A. De Antoni, and C. Costa, and was critical in assuring the viability of the new organization. Subsequent meetings were held in 1977 in Madison, Wisconsin (USA), organized by R.R. Brown, D.P. Rose, and W.E. Knox, honoring C.P. Berg; 1980 in Kyoto (Japan), organized by O. Hayaishi, R. Kido, Y. Ishimura, T. Deguchi, T. Hino, T.

The advent in the 1960s of the unique and exciting new form of energy called laser brought to medicine a marvelous tool that could accomplish new treatments of previously untreatable disorders as well as improved treat ment of mundane problems. This brilliant form of light energy is many times more powerful than the energy of the sun yet can be focused microscopically to spot sizes as small as 30 microns. Lasers can be directed into seemingly inaccessible areas by mirrors or fiberoptic cables or can be directly applied into sensitive areas such as the retina without damage to intervening structures. There has been a rapid proliferation in the use of lasers in all surgical specialties. Starting with bold ideas and experiments of "thought leaders" in each specialty, the application of lasers has evolved into commonplace usage. Beginning with the era when laser presentations and publications were an oddity, now nearly all specialty areas have whole sections of meetings or journals devoted exclusively to laser usage. Laser specialty societies within a specialty have developed and residency training programs routinely instruct trainees in laser techniques. Basic science and clinical experimentation has supported laser knowledge. Laser usage has also become international. Newer wavelengths and accessories have added to the armamentarium of laser usage. Despite the rapid growth in laser interest, no single source exists to instruct the many new laser users in proper, safe, and effective use of this new modality."

A growing majority of women in the western hemisphere have been delaying initiation of childbearing to later in life. Consequently, more than ever before, women in their late 30s to early 40s are attempting their first pregnancy. Since the incidence of most cancers increases with age, delayed childbearing results in more female cancer survivors interested in fertility preservation." Fertility Preservation in Females: Emerging Technologies and Clinical Applications" contains a selection of the valuable chapters and protocols of Seli and Agarwal s previously published hardcover text "Fertility Preservation: Emerging Technologies and Clinical Applications." Newly available in this convenient and affordable softcover format, this unique and practical reference guide for reproductive endocrinologists, gynecologists, embryologists, reproductive scientists, and oncologists provides strategies for fertility preservation in women, using a format that combines concise scientific background with practical methodological information and easy-to-grasp algorithms."

Rodney Appell, and a host of respected clinical experts comprehensively summarize the state-of-the-art in the diagnosis and treatment of both neurogenic and nonneurogenic urinary problems in males and females alike. Tailored for use by today's busy practicing urologists, as well as frontline physicians, this book provides the essential physiological background for classifying voiding dysfunctions, surveys the practical diagnostics for these dysfunctions, and reviews the available treatments, including pharmacologic therapy, electrical stimulation, and surgery. Informative, practical, and clinically relevant, Voiding Dysfunction: Diagnosis and Treatment brings to every physician's treatment room a first-class compendium of the latest scientific facts, the best methods of diagnosis, and the most appropriate and effective treatments for these disturbingly widespread disorders.

In 1962 in the series Handbuch der Urologie - Encyclopedia of Urology - Ency- clopedie d'Urologie the roentgen examination of the kidney and ureter was extensively presented by the present author in collaboration with Gosta Jonsson. The roentgen exa- mination of the distal genital tract and the male genital organs was presented by Lind- blom and Romanus. In the corresponding series Handbuch der Medizinischen Radiologie - Encyclopedia of Medical Radiology ten years later, we have arrived at the publication of the roentgeno- logy of the kidney and the urinary tract. It was felt expedient that the entire chapter on urologic roentgenology be revised by the present author on the basis of a greatly enlarged current material from the Department of Diagnostic Radiology, University Hospital, Lund, Sweden. This hospital is a regional university hospital for a population of approxi- mately 1,200,000 inhabitants in southern Sweden. Patients with specific problems for qualified diagnostic and therapeutic procedures are referred to Lund from other hospitals within the region, both central and local hospitals, and consulting cases are sent from very wide distances.

"People . . . see you sweat in agony, turn pale, turn red, trem ble, vomit your very blood, suffer strange contractions and con vulsions, sometimes shed great tears from your eyes, discharge thick, black and frightful urine, or have it stopped up by some sharp rough stone that cruelly pricks and flays the neck of your penis. " * These 16th century frustrations of Michel de Montaigne which most graphically reflect his experience with renal colic still plague approximately 1 per 1000 individuals in the United States annually. Since as many as 75% of clinically. apparent episodes of renal colic represent single nonrecurring events, physicians not in frequently approach the differential diagnosis of nephrolithiasis in a less than adequate fashion and assume that the incident may prob ably never recur after the single attack. However, the ureteral or bladder stone actually represents one form of abnormal crystalline precipitation; parenchymal nephrocalcinosis, silently progressive azotemia, and asymptomatic renal pelvic calculi may also stem from the same pathological process(es) which conditioned the for mation of the ureteral or bladder stone. In this regard it is worth emphasizing that the postmortem incidence of renal calculi is some tenfold greater than that presumed from surveys wherein a clinical attack of nephrolithiasis is the sole determinant. *In Familiar Medical Quotations. M. B. Strauss, Ed. Little Brown, Boston, 1968, p. 646. v vi FOREWORD The last decade has witnessed the birth of new knowledge in urolithiasis research."

Ferment, a sign of progress in any scientific field, has previously been lacking in the area of cryptorchidism, where the only activity has been in improving operative methods. Now, however, profound changes in the care of boys with cryptorchidism are being brought about; ideas are arising from a fresh look at comparative anatomy, and histological and experimental observa tions are being supplemented by clinical tests made possible by new hormonal agents. The treatment of cryptorchidism begins with its recognition by the pediatri cian, who until now has shown little interest because of disappointing results from chorionic gonadotropin administration. As for the surgeon, his bent toward restoration of normal anatomical relationships has kept his attention focused on the development of better surgical technics to bring the recalci trant testis into the scrotum. Both specialists have avoided the primordial question of why the testis did not descend properly. If this were known they would treat the cause of cryptorchidism, and not be satisfied merely with trying to correct its end result. As one reads this book, one sees that in most patients cryptorchidism is not caused by some anatomical structure blocking the way or by some deformity of the testis interfering with the transport mechanism. Rather, deficiencies in the hormonal environment of the fetus retard the developmen tal sequences essential to the normal differentiation and descent of the testis. The clinical solution is thus to provide the deficient substances."

Knowledge about cancer genetics is rapidly expanding, and has implications for all aspects of cancer research and treatment, including molecular causation, diagnosis, prevention, screening, and treatment.

Additionally, while cancer genetics has traditionally focused on mutational events that have their primary effect within the cancer cell, recently the focus has widened, with evidence of the importance of epigenetic events and of cellular interactions in cancer development. The role of common genetic variation in determining the range of individual susceptibility within the population is increasingly recognized, and is now being widely addressed using information from the Human Genome Project. These new research directions will highlight determinants of cancer that lie outside the cancer cell, suggest new targets for intervention, and inform the design of strategies for prevention in groups at increased risk.

Today, the NCI is putting more and more money into research into the genetics of cancer. The very first of the NCI s stated research priorities is a project called The Cancer Genome Atlas. The Cancer Genome Atlas (TCGA) is a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing. The NCI and the NHGRI (National Human Genome Research Institute, where the series editor is employed) have each committed $50 million over three years to the TCGA Pilot Project.

This book proposes cover the latest findings in the genetics of male reproductive cancers; specifically cancers of the prostate and testes. The volume will cover the epidemiology of these cancers; model systems, pathology, molecular genetics, and inherited susceptibility."