The subject of the Sixth Symposium on Clinical Oncology of the Royal College of Radiologists held in February 1984 was ovarian cancer. This publication presents the collected papers delivered at that meeting, but excludes much useful discussion which also took place. The annual clinical oncology symposia have been designed to re- view topics of current interest in cancer therapy from a multidis- ciplinary point if view. It was gratifying to the organisers and all who took part that the aims were so well met by both the contrib- utors and discussants. We believe that this can only be to the ad- vantage of future research and our present and future patients. Ovarian cancer is a common gynaecological cancer which freqently presents late. Its clinical management is bedevilled by the variable referral routes through which patients present for treatment. Thus, many are first seen by general abdominal sur- geons who may not be expert in their treatment, rather than gynaecologists or gynaecological oncologists. There are many in- teresting features about it which have been discussed by the var- ious speakers. Early spread within the abdomen is common, spread outside the abdomen less common. There is a variety of histopathological types, each with distinct aetiological, prognos- VI Preface tic and therapeutic assocations. In contrast to most cancers, sur- gical debulking of tumour is considered valuable even when there is no possibility of removing all tumour by the knife.

It is about 15 years since the first presentation on uteroglobin was given to a group of developmental biologists, reproductive physiologists, and geneticists who had gathered in November 1966 at Konstanz (Germany). In the following decade so much knowledge was accumulated that a special symposium seemed appropriate. This was organized as a satellite symposium to the International Congress of Endocrinology at Hamburg and brought together 50 scientists at Aachen. These scientists, working in the field of pro teins and steroids, in early pregnancy, recognized the impact of what had been reported, and many of them later agreed to contribute to this booN. and thus to present their research d, ta available until December 1980. The present volume covers a relatively broad spectrum of data and observations which shed some light on preimplantational embryonic life and on the supports and obstacles provided by the maternal organism with respect to final accomplishment of normal im plantation and establishment of pregnancy. The book will serve both as a textbook and as a scientific dictionary for Ph.D. students, postdoctoral fellows and advanced scientists working in this area. The course of early pregnancy depends very much on a proper balance of steroid hor mones, and the induction of protein synthesis by steroid hormones is one of the well known fundamental processes in cellular differentiation and embryonic development."

I am honored to have been invited to write a foreword for this book, because tumors of the yolk sac have been a preoccupation of mine since the days of my residency, now more than 3 decades ago. At that time, a 3-year-old boy died of a testicular cancer of unknown histo genesis. It was bad enough that the child died, but it bothered me even more that medical science did not know the histogenesis of the tumor that destroyed him, and I decided to study testicular cancer. For re search training I sought out F. J. Dixon, who had written the Armed Forces Fascicle on testicular tumors. Dr. Dixon and I showed that embryonal carcinoma was a multipoten tial malignant stem cell that differentiated into the three embryonic germ layers of murine teratocarcinoma. This led to the idea that the normal counterpart of embryonal carcinoma must also be multi potent, and we focused on the preimplantation embryo for the histo genesis of the tumor. This idea was strengthened by the discovery that embryonal carcinoma cells made embryoid bodies in the ascites and it was possible to observe the development of these bodies in vitro. These observations led to the idea that embryonal carcinoma was a caricature (gross misrepresentation) of early development, and car cinomas in general were a caricature of the process of renewal of their normal counterpart."

Reevaluation of tumor classification, differential diagnosis and differential therapy based on modern knowledge. Revision of all chapters to incorporate new facts based on recent discoveries.

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 authors of this book have a goal-to describe the management of infertility from the perspective of physiology and anatomy gone awry. To accomplish this goal, the chapters devoted to the causes of infertil ity begin with a description of the normal structure and function of the organ or system causing the infertility. We believe that under standing the normal will result in rational and effective diagnosis and treatment of infertility. Our intent is that this book be a useful re source for those who care for infertile couples. For an infertile couple, success is the delivery of a normal and healthy infant. Chapters that describe the causes and treatment of habitual abortion and the reproductive performance of previously infertile couples emphasize the hazards that exist between conception and birth. Our environment is one of these hazards, one that may also affect reproduction before conception. A chapter is devoted to a de scription of environmental agents that affect reproduction, the mech anisms of their effect, and methods to predict those present and future environmental agents which might also affect reproduction."

In 1909 a short contribution entitled "Geriatrics" was published in the New York Medical Journal. According to this article, old age represents a distinct period oflife in which the physiologic changes caused by aging are accompanied by an increasing number of pathologic changes. We now know that the organs of the body age neither at the same rate nor to the same extent and that physiologic alterations are indeed superimposed by pathologic changes; as a result of the latter phenomenon the origins and course of illnesses in the elderly can present unusual characteristics. The frequency of concurrent disorders in the elderly entails the danger of polypragmatic pharmacotherapy, i. e., the use of various drugs to combat various disorders while neglecting the possibly adverse combined effects of these drugs. To obviate this danger, special knowledge in the field of geriatrics, the medical branch of gerontology, is necessary. Geriatrics is constantly increasing in importance owing to the near doubling of life expectancy over the past 130 years and to the improved diagnostic and therapeutic techniques made available by medical pro gress. The rapid recent development of experimental gerontology has played an essential role in enabling us to understand the special features of geriatrics. This progress has, however, been accompanied by such a vast increase in the volume of literature on the subject that specialists in the field can scarcely maintain an overall perspective of new publications."

In few areas of medicine is progress more spectacular than in the field of prenatal diagnosis. New clinical techniques such as chorion villus sampling, detailed ultrasound scanning and cordocentesis are being evaluated by obstetricians, and refinement of biochemical testing is widening the scope of maternal serum screening. In the laboratory, dramatic advances in molecular biology are occurring: families at risk of genetic disease can be investigated with gene probes, and preimplantation diagnosis of the embryo is now becom ing a reality. These technical advances have important ethical and practical implications, among which will be a further increase in public expectations of the standards required of antenatal services. Clini cians will need a high degree of skill to inform healthy women about the options for screening normal pregnancies, and to counsel high-risk women about the benefits and limitations of prenatal diagnosis. Obstetricians, scientists and health service managers will face the difficult task of deciding how prenatal diagnosis can be made available to women in a caring and cost-effective way. Recognising the rapid progress in this field, the Royal College of Obstetricians and Gynaecologists made prenatal diagnosis the subject of its 23rd Study Group. An international panel of leading researchers, whose expertise ranged from molecular biology to philosophy, was invited to participate in a three day workshop, with time for in-depth discussion as well as the presentation of papers.

In the past decade fetal heart rate monitoring has become a generally ac cepted method for fetal surveillance during pregnancy and labor. Although its importance has been doubted recently, I personally feel that this method has become an important obstetric tool. It has not only improved our knowledge about fetal behavior and fetal condition throughout gesta tion, but it has especially improved fetal surveillance during labor; the most dangerous period of human life has never been as safe as nowadays. The only people who can question the advantage of fetal heart rate moni toring are those who did not experience the period before fetal heart rate monitoring was generally introduced. The first paper on the history of fetal heart rate monitoring takes us back to the beginning of fetal surveillance and provides an introduction to the different aspects of fetal observation which are covered later in this volume. Common practices of fetal surveillance in different countries are discussed, and the paths that future developments will take are suggested. An outline of the physiological aspects of fetal heart rate regulation is fol lowed by discussion of the pathophysiology with which the obstetrician is very often confronted."

Important contributions about the treatment modalities of breast cancer are presented in this book. The risks and limitations of breast conserving therapy of mammary carcinoma are dealt with. Newest findings show that this form of therapy has the same outcome as conservative treatment modalities. The book also considers controversial issues such as the treatment of mastopathy, precancerous, and non-invasive lesions of the breast. New, but not yet approved, regimes for the prevention of mammary carcinoma and open questions concerning adequate operative treatment are discussed. Latest results presented here show that all modern palliative chemotherapy has a certain but limited effect on outcome and that early detection and preventive therapy (surgical and hormonal) will be of great importance for improved chances of survival of breast cancer.

It will be a long time before the quality of this profusely illustrated book is overtaken and the present spate of books on the subject of obstetric ultrasound may, as a result, suffer a numerical set-back - especially with translation into English which will "deliver the milk on everyone's doorstep". Two of the authors studied in our department in Glasgow and worked like If there are any rewards for teaching, then we humble Scots who demons. have had the privilege have had more than our share as a result of the pride with which we regard our pupils. In my own old age and looking back over the last thirty years, the innumer able difficulties, set-backs and disappointments have been more than compen sated for by those who have turned the subject from a laughable eccentricity (as I have at one time experienced) into a science of increasing exactitude. This transformation has come about, not by any efforts of mine, but by the enthusiasm and ingenuity of those who would probably have achieved as much on their own if given the encouragement which I ultimately received in Glasgow University life. Limbo must be the expected lot of most of us ordinary mortals but the work lives on. And so, in this reminiscent and philosophical mood I beg leave to quote a little poem which I wrote at an age when young men do that sort of thing.

HRT and Osteoporosis is a response to the increasing awareness among both the medical profession and the general public that ovarian failure is an important cause of osteoporosis and that much of the bone loss after the menopause can be prevented by oestrogen treatment. There is now an urgent need on the part of women, their doctors and those responsible for public health policy for practical guidance on such questions as the safety and acceptability of long-term treatment with sex hormones, the economic costs and benefits of such treatment, and the role of specialists and GPs in promoting and monitoring hormone replacement therapy. All these issues and more are considered here. The book comprehensively reviews current knowledge of the subject and gives recommendations for clinical practice and future research.

Infertility, as with many aspects of medicine, is at the mercy of rapid technological advance. Many of these developments initially seem attractive to both clinicians and patients, but need to be rigorously assessed if their real value is to be understood and clinical practice is to develop. In this book issues of importance to the management of infertile patients are discussed. The gaps in our knowledge which prevent a better understanding of the condition are identified, and recent developments, both clinical and scientific, are subjected to peer review and discussion. An important feature of the book is an acceptance that training in infertility practice is a real problem. This is perceived not only by the practising clinicians, both doctors and nurses, but particularly by the clinical scientists, including embryologists, who now provide such an essential part of the service. Similarly the provision of the clinical service has been examined in detail from a variety of standpoints, in an attempt to make sensible recommendations which balance real need with limited resource. The book is based on the papers presented and discussed at the 25th RCOG Study Group held in April 1992. The discussion after each paper was civilised but uncompromising and forms an important part of this publication. The rapid processing of the written and recorded material by the staff at the RCOG, and particularly Miss Sally Barber, has ensured that the book has been produced while the issues are live, the reviews contemporary and the discussion relevant.

This book is the product of long years of close collaboration between two physicians, a pediatric endocrinologist and a pediatric surgeon, who are interested in the complex field of human malformations. Their efforts have set a new standard in the treatment of children with intersexual or mal formed female genitalia. It is impossible to convey the details of complex surgical procedures without the help of meticulous illustrations. It is fortunate that happened to meet an academically trained artist, Mrs. Siri Mills, M.A., while visiting in the United States. Her excellent knowledge of anatomy, her remarkable skills as an artist and technical illustrator, and her readiness to include all details of interest to the surgeon have found their fruitful expression in the illustrations of this book. We express our thanks to Springer-Verlag and especially to Prof. Diet rich Goetze, at whose suggestion this book was written, for their amiable compliance with all our wishes, and particularly for their willingness to retain Mrs. Mills as our illustrator. Munich, May 1985 WALDEMAR HECKER Contents In trod ucti on 1 Part 1: Endocrinologic Diagnosis in Pediatric Patients with Genital Anomalies General Rules . . . . . . . . . . . 4 Endocrinology of Antenatal Sex Differentiation 6 Male Differentiation 6 Female Differentiation 7 Specific Endocrinologic Diagnosis and Therapy 8 Virilization of the Female External Genitalia 8 Congenital Adrenogenital Syndrome with a Defect of 21-Hydr- ylase . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Intersexual Genitals Due to Deficient Androgenization of the Male 11 Defects of Testosterone Biosynthesis 11 Androgen Receptor Defects . . ."

Many of the studies discussed in this book were addition to discussions of a variety of hormonal, presented at the First Pan American Congress of biochemical, immunological, physical, and me Andrology, which was held in Caracas, Venezuela, chanical approaches. It is our hope that the efforts in March 1979. An international group of in of the contributors will help to intensify research vestigators have contributed reviews designed to and development of improved methods for safely be informative to medical, graduate, and post regulating male fertility. graduate students, as well as clinicians and in vestigators working in the area of male reproduc G. R. CUNNINGHAM tion. Current physiological concepts that may W. B. SCHILL provide insight for new initiatives are examined in E. S. E. HAFEZ TABLE OF CONTENTS Preface v Contributors IX Foreword by C. SCHIRREN XI 1. PHYSIOLOGY OF MALE REPRODUCTION 1. Hormonal regulation of testicular function 5 P. FRANCHIMONT 2. Inhibin: new gonadal hormone 15 P. FRANCHIMONT, A. DEMOULIN, J. VERSTRAELEN-PROYARD, M. T. HAZEE-HAGELSTEIN, and J. P. BOURGUIGNON 3. Morphological features of the epididymis: possible significance in male contraception 25 T. D. GLOVER 4. Regulatory physiology of male accessory organs 35 E. S. E. HAFEZ and G. R. CUNNINGHAM 5. Methods for evaluating contraceptive techniques 41 T. Z. HOMONNAI and F. G. PAZ II. HORMONAL CONTRACEPTION 6. Inhibition of male reproductive processes with an LH-RH agonist 55 A. CORBIN and F. J. BEX 7."

Over a mere 5 years, neonatal cranial sonography has evolved from an obscure and largely experimental imaging possibility to the modality of preference in the examination of the young brain. The almost immediate acceptance of the ultrasound examination of the neonatal brain was based on a number of coinci dent factors, the most important of which was the emergence of a burgeoning population of premature neonates who were, for the first time, surviving be yond infancy. These delicate patients were beginning to withstand the rigors of extrauterine life when not fully prepared for it; pulmonary, cardiac, and infec tious diseases no longer claimed most of them. With survival, a new specter reared its head: Would the eventual mental and neurologic status of these same children be worth the expense and time needed to bring them through their first months? This issue became increasingly pressing as evidence mounted through the 1970s that very premature neonates were at a high risk for intracranial hemor rhage and posthemorrhagic complications. An imaging modality that could evaluate the premature brain was sorely needed. The CT scanner with its proven ability to diagnose intracranial hemorrhage was of little value in this regard. So too were static gray-scale or waterpath ultrasound units. These modalities all had the same limitation, lack of portability. As neonatal intensive care units proliferated, so did the technology that would soon allow cribside neonatal neuroimaging, the real-time sector scanner."

The purpose of this series of volumes is to present a comprehensive view of the complications that result from the use of acceptable diagnostic and thera peutic procedures. Individual volumes will deal with iatrogenic complications involving (1) the alimentary system, (2) the urinary system, (3) the respiratory and cardiac systems, (4) the skeletal system and (5) the pediatric patient. The term iatrogenic, derived from two Greek words, means physician-in duced. Originally, it applied only to psychiatric disorders generated in the patient by autosuggestion, based on misinterpretation of the doctor's attitude and comments. As clinically used, it now pertains to the inadvertent side effects and complications created in the course of diagnosis and treatment. The classic categories of disease have included: (1) congenital and developmen tal, (2) traumatic, (3) infectious and inflammatory, (4) metabolic, (5) neoplastic, and (6) degenerative. To these must be added, however, iatrogenic disorders a major, although generally unacknowledged, source of illness. While great advances in medical care in both diagnosis and therapy have been accomplished in the past few decades, many are at times associated with certain side-effects and risks which may result in distress equal to or greater than the basic condi tion. Iatrogenic complications, which may be referred to as "diseases of medical progress," have become a new dimension in the causation of human disease."

In recent years, papillomaviruses in general and human papillo maviruses in particular have been recognized as possible agents of important diseases, including some forms of human cancer. The purpose of this book is to present a concise panorama of the pre sent status of knowledge of this topic. This knowledge is as impor tant to molecular biologists and virologists as it is to clinicians and pathologists. To bridge the gap among these diverse groups of investigators, we conceived of a book covering a broad spectrum of the basic scientific, clinical, and pathological aspects of diseases associated with papillomaviruses. Although the principal thrust of this book is directed at human papillomaviruses, fundamental knowledge of animal viruses is essential to the current understand ing of the molecular mechanisms of cell transformation. For this reason, a chapter on animal viruses has also been included. Some of the experimental work having to do with the elucidation of transformation and other aspects of interaction between the virus and the cell cannot be based on human papillomaviruses because of a lack of suitable experimental models. Hence, some of the chapters dealing with fundamental aspects of viral molecular biol ogy are based on animal models. We were very fortunate in having persuaded a number of distin guished colleagues to contribute to this work."

Postpartum Depression: Causes and Consequences chronicles a decade and a half of research into this relatively common mood disorder experienced in various forms by between 10-40% of all women following delivery. The author has conducted three major studies all of which are presented in this volume. The most recent study comprises the bulk of the monograph and presents the results with regard to psychological, social and hormonal factors in postpartum depression and the blues. Information regarding the epidemiology, etiology and treatment of postpartum depression is also included. The work described in this volume represents the attempt by the author to begin to address several of the major unresolved questions regarding the prevalence, causes, and consequences of postpartum mood disorders. The important negative implications of poor maternal adjustment for both the new mother and her family as well as the increased awareness of childbearing women who are now demanding answers and information make this book indispensable for all practitioners in psychology, psychiatry and obstetrics-gynecology as well as for the students of these disciplines.

This volume contains the papers on family planning research which were presented at the XIth World Congress on Fertility and Sterility held in Dublin, Ireland in June, 1983 under the auspices of the International Federation of Fertility Societies. These papers were presented during the related communi cations sessions of the Congress and have been brought together into a special volume which will be of major interest to those concerned with family planning. Section 1, deals with the area of natural family planning, determination of the fertile period and effects of lactation. Steroid contraception, vaginal and intrauterine contraception, abortion and sterilization are included in Sections 2-4. Social aspects of fertility control are covered in Section 5 and the final section contains studies of the effects of gossypol as a male contraceptive. This volume brings together important new knowledge in the area of family planning, clarifies some of the problems and should stimulate research on the many unresolved issues in this vitally important area."

A Woman With Cancer Deborah came to University Hospital when she was 25. She was the mainstay of a young farming family. Her husband, Merle, was now farming his family land, working hard to keep financially solvent during these difficult f;lrming days. They had four children: Carolyn, 4 months; Michael, 17 months; John, 4 years; and Susie, 5 years. There was nothing special about this woman or her circumstances; she was like every woman who had ordinary daily chores and responsibilities, people in her life about whom she cared and who cared for her, worries, goals, dreams, and her life before her. Deborah's 4-week postpartum checkup and Pap smear were normal; however, six weeks later she had heavy, irregular bleeding. To Deborah this symptom picture did not seem to fit the pattern of her other preg nancies, and so she returned to her doctor. A large lesion was found on the posterior cervix and biopsies of the tissue revealed moderately dif ferentiated adenocarcinoma of the cervix. Referral to the University Hospital 60 miles away confirmed the diagnosis. Further tumor workup, which included a pelvic ultrasound, bladder cystoscopy, sigmoidoscopy, and chest x-ray, was normal, although the IVP was notable for nonvi sualization of the right ureter, thought to be secondary to an enlarged lymph node."

This volume contains the Proceedings of the Serono Symposium on Pre implantation Embryo Development, held in Newton, Massachusetts, in 1991. The idea for the symposium grew out of the 1989 Serono Symposium on Fertilization in Mammals* at which preimplantation development was the predominant suggestion for a follow-up topic. This was indeed a timely subject in view of the recent resurgence of interest in this funda mental phase of embryogenesis and its relevance to basic research and applied fertility studies in humans, food-producing animals, and endangered species. The symposium brought together speakers from a broad range of disciplines in order to focus on key regulatory mechanisms in embryo development, using a wide variety of animal models, and on representative topics in human preimplantation embryogenesis. The culmination of preimplantation development is a blastocyst con taining the first differentiated embryonic tissues and capable of initiating and sustaining pregnancy. The central objective of the symposium was to throw light on the regulation of cellular and molecular events underlying blastocyst formation. It was particularly appropriate that the date of the symposium marked the 20th anniversary of the publication of the classic volume Biology of the Blastocyst, the proceedings of an international workshop held in 1970. This book, which summarized most of the information then available on this topic in mammals, was edited by the pioneer in blastocyst research, Dr. Richard B1andau, who was the guest speaker at the symposium."

Views and attitudes. towards termination of pregnancy have shown con siderable evolution over the past few decades. Along with these changes has come a growing concern to adopt means and methods which could make termination easier, safer and more effective. In this evolution, termination in the second trimester in par icular is notable as being responsible for a dis proportionate share ofthe complications and adverse experiences associated with pregnancy termination. Although the almost universal shift towards earlier abortion has reduced the number of second trimester procedures as a percentage of the whole, the problems of interrupting pregnancy in the second trimester remain conspicuous. Delay in either seeking or obtaining abortion is still, in many parts of the world, all too frequent. AdditiDnally, recent developments in the prenatal diagnosis of fetal malformations, alphafeto protein screening programmes and changes in the pattern of and approaches to intrauterine fetal death now also place greater emphasis on the need for adequate methods of interrupting pregnancy in the second trimester. Unlike the first trimester in which vacuum aspiration is universally con sidered to be the method of choice, in the second trimester of pregnancy the clinician is faced with alternatives; one method may be more appropriate than another in a particular circumstance and no single method is unequivocall accepted as best. Neither do second trimester terminations form a neatly defined single category."

Third edition of the atlas discussing pathophysiology, epidemiology, diagnosis, prevention and treatment of postmenopausal osteoporosis, as well as the importance of bone quality and strength in fracture risk.

Fully illustrated with over 120 full colour images
Thoroughly revised and updated new edition
Written by a team of world-leading experts in bone health

Although neonatal screening was begun only 20 years ago, and is consequently still in its early stages, it is already a classic example of efficient preventive pediatrics. At present, routine neonatal screening covering a satisfactory percentage of newborn babies is carried out in only a small part ofthe world. For some five diseases enough infants have been screened to give reasonably reliable information about the frequency of these diseases in various populations. Interesting differences are beginning to appear in popula tions of different ethnic and racial background. The medical importance of neonatal screening is especially obvious in metabolic diseases that are not too rare and for which effective treatment depends upon an early diagnosis, such as phenylketonuria, galactosemia, and - a more recent screening pro gram - hypothyroidism. About 1 of 4000 newborns is affected with hypothyroidism and can receive timely substitution with thyroid hormone. Of 34.5 million babies tested for phenylketonuria, 3000 cases have been diagnosed in time to prevent mental retardation by means of dietary therapy."