Changing approaches to diagnosis and clinical management of the uterus are comprehensively examined in this book. It gives a concise update of new concepts in physiology and pathology and their application in clinical practice. The book is designed especially for the gynecologist actively involved in patient care. Topics discussed include the pathophysiology of diethylstilbestrol (DES) changes, the immunology of the uterus, papillomaviruses and cervical neoplasia, endocervical carcinoma, mesenchymal tumors and diagnostic procedures such as colposcopy of the cervix, hysterosalpingography, and magnetic resonance imaging. The status of contemporary management is presented for hysteroscopy and hysteroscopic surgery, the congenital absence of the uterus and vagina, anovulatory dysfunctional uterine bleeding of the adolescent, uterine leiomyomata, genital prolapse, endometrial adenocarcinoma and childhood rhabdomyosarcoma of the vagina and uterus.

Medical ethics is a difficult and controversial field and that part of it dealing with reproductive medicine is no exception. Our first conference on philosophical ethics in reproductive medicine (PERM 1) in 1988 discussed many of the controversies in this field. The acclaim it received encouraged us to organise PERM 2 but choosing a relevant and topical programme was a clairvoyant challenge in its own right. Since PERM 1 we have seen a number of developments, in the UK and internationally, that have thrown the problems that society must face into sharp relief. Drawing on the expertise of contributors from science, many medical specialities, philosophy, theology and economics, we have sought to address the issues raised by these new developments, as well as a number of long-standing issues that remain as contentious as ever, but of undiminished significance. On the scientific front, the long-predicted technique of embryo biopsy and diagnosis is now a reality. This has prompted the inclusion of some of the topics addressed by this second conference.

Sexual medicine is an interdisciplinary subject. Special knowledge of normal and disturbed sexuality is expected of general practitioners, gynecologists, dermato logists, urologists, specialists in internal medicine, neurologists, psychiatrists, and psychotherapists. Sexual dysfunctions may occur in connection with organic lesions or as psychosomatic phenomena. They are brought to the practicing physician's attention by the patient either directly or in the form of factitious symptoms. The disturbed sexual function generally causes suffering and so motivates the patient to consult a physician. Psychosomatic aspects are thus very much to the fore. In a significant number of cases, however the disturbances stem from a physical-functional handicap which not only affects the patient's general personality but also has a direct adverse effect on sexual function. The physical defect leads to disturbances of the body-image, and so can cause impairments in the sexual sphere both directly and indirectly. The diseases which result in sexual handicap and which can be treated by reconstructive surgery were examined and discussed at an international satellite symposium of experts on the occasion of the 8 th World Congress for Sexology in June 1987. The papers presented at this symposium have been collected and edited in this volume."

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."

Endometriosis provides a unique clinical and scientific challenge. It is being diagnosed with increasing frequency and yet we are unsure of the significance of this in many patients. Its appearance varies from a tiny focus of disease to a potently destructive phenomenon. Weare still unsure of the relative value of medical or surgical treatment. The pathogenesis and control of the cellular function of the disease proVide many scientific problems. The presence of a comparative normal epithelium, namely endometrium, provides a unique research opportunity. It is probable that only through basic science research will we be able to solve the clinical dilemmas that endometriosis presents. We felt that it was important to create a book that explored the important scientific and clinical problems. We therefore invited acknowledged experts from both Europe and the United States of America to review their fields. The purpose of these reviews is not only to provide a resource for clinicians and scientists but also to stimulate thought and new ideas for research and treatment. To fulfil that aim we have asked that the authors be more speculative than normal for a volume such as this. We thank them for responding to their task so well and hope that you will feel as stimulated by their efforts as we have been.

I am very happy and honoured to have so many famous contrib utors from around the world presenting their knowledge and experience in this book, including Dr. Rufer who, as early as 1967, attempted to improve the pressure-volume curve of a child dying from RDS using dried surfactant from dogs; Drs. Enhorn ing and Robertson who were the first to treat rabbit fetuses with surfactant replacement and impressively demonstrated that sur factant improved lung mechanics; and Dr. Fujiwara who at the end of the 1970's had already successfully treated the first babies with surfactant replacement and published this work al ready in 1980. Thus, the idea of surfactant replacement therapy is now more or less 20 years old and almost 10 years have passed since the first publication by Dr. Fujiwara of his impressive clinical results. Up to now (September, 1988) about 2,200 babies have been treated worldwide with tracheal instillation of surfactant, with most promising results. The type of surfactant used varies from pure natural extracts from bovine or pig lungs, to surfactant extracted from human amniotic fluid, to pure phospholipids. To date, however, there is still no surfactant commercially available (except in Japan), in spite of the fact that it is urgently awaited by neonatologists and intensive care doctors throughout the world. This volume is based on the contributions presented at the international congress on Surfactant Replacement Therapy which was held in Rotterdam, The Netherlands, in November 1987."

Perinatal medicine, which is concerned with the problems of the fetus and newborn, has rapidly developed in the last two decades as an important and challenging specialty. Rapid advances in the field, coupled with tech nological advances, now are making survival of infants with weights as low as 500 grams possible. Ventilator care for severe respiratory problems is on the verge of being replaced by surfactant replacement therapy; on the other hand, development of such technologies as extracorporeal mem brane oxygenation and jet ventilation has revolutionized the care of these sick infants. The advances taking place today in the field of perinatal medicine make periodic updates, like the one provided by this volume, a virtual necessity for clinicians and paramedical personnel alike. A distinguished group of specialists in various aspects of perinatal medicine has contributed to this book. Their wide-ranging experience and points of view should make this book a valuable reference for all physicians and allied health personnel involved in the care of the high-risk fetus and newborn. MANOHAR RATHI, M.D. Acknowledgements. I am grateful to the contributors for their cooperation in preparing the manuscripts, to my associates for their help and support, and to the publishers for their continued interest in this work. Above all, I thank Ms. Rose Aiello-Lech and Ms. MaryAnn Cichowski for their hard work in making this publication possible."

Few subjects in gynecology, let alone in medicine in general, have provoked such inter est or study as cervical cancer. Although the wealth of monographs and books publish ed on the subject would seem to obviate the need for more, the great advances made in the medical sciences and in gynecological experience and techniques in recent years call for, if not require, a new book on cervical cancer to bring together the latest ideas and trends in its methods of study, diagnosis, and treatment. Although precancerous lesions have become more common, the number of women developing invasive cervical carcinomas has not increased, owing in part to programs of patient education, in part to screening examinations sponsored by the government. The gynecologist is now able to detect with well-tried and proved techniques precan cerous states of the cervix, and to treat these effectively before they become invasive cancer. Accordingly, recent interests in cervical cancer have shifted from the classic descrip tion of invasive carcinoma to newer studies of cause, diagnosis, therapy, and terminol ogy of its precursors. As the reader will learn, epidemiological studies as guides for the future account for, and justifiably so, an important part of this book. New knowledge about changes in the morphology of cervical carcinoma confirms its dependency on hormonal stimulation. Furthermore, modem experiences serve to explain which therapy is best. Overlapping of concepts and opinions between some chapters could not be avoided."

H.-J. Senn Adjuvant Chemotherapy (ACT) of breast cancer has now emerged as one of the controversial su):>jects in clinical and also experimental oncology. Driven by growing frustration about stagnating cure rates in breast cancer [1,4] and stimulated by elegant demonstration of highly curative effects of adjuvant systemic therapy in animal models [6, 11] and in several childhood neoplasias [15], researchers introduced ACT to the primary treatment of breast cancer with great hope some 15 years ago. After a first wave of isolated "historic" trials with generally limited but in one case remarkable success [5, 9], a second generation of ACT studies was initiated by NSABP investigators and oncology centers in Europe [2, 6, 13]. These trials were well conducted statistically and diagnostically, and all in the early 1970s included a surgical control arm. Early and intermediate beneficial effects on relapse-free survival (RFS) after 2-3 years median observation time then prompted a whole series of ACT studies in breast cancer. These "third-gener ation" studies usually regarded some positive influence of ACT as a given fact, dropping surgical control regimens and comparing different ACT regimens, hopefully in a prospective, randomized way 1984 Fig. 1. The mushrooming of adjuvant studies in breast cancer XII Introduction [reviews in 3, 14]. The "mushrooming" of ACT studies in breast cancer during the last 10 and especially 5 years is demonstrated in Fig. 1, and it gets really cumbersome even for the insider to keep on top of the multitude of sometimes conflicting data.

A. CORBIN Investigations on LHRH and its analogs have just completed their first decade. We have witnessed a veritable explosion of chemical, physiologic and pharmacologic data on this hypothalamic peptide and the approximately 1500 agonist and antagonist analogs that have been synthesized. In order to track this expanding field, I was asked to organize an international symposium on basic and clinical aspects of LHRH analogs as part of the Reproductive Health Care: CDS Symposium held in Maui, Hawaii, in October 1982. This meeting brought together a number of the leading investigators in the field. Much new state-of-the-art information was presented which I and my colleagues felt deserved a wider audience. Drs Vickery, Nestor, and Hafez consented to undertake this task. Upon review of the literature, it was apparent that there was no recent text which fully covered the breadth of developments in the field. Accordingly, the editors decided to use the symposium as a nucleus on which to build a singular, comprehensive state-of-the-art analysis of this rapidly growing discipline, and the application of such knowledge to reproductive medicine. As exemplified by the various areas of expertise provided by the individual contributors, it becomes obvious that the scope of the subject matter, while relating solely to a well-defined chemical class (LHRH analogs) and a circumscribed physiologic and pharmacologic entity (reproduction), has expanded enormously.

The Interfaces of Perinatal Addiction Ira J ChasnofT In the last few years, problems associated with drug use in pregnancy have become endemic. As cocaine has become the drug of choice for millions of Americans, including pregnant women, as AIDS has become more commonly recognized in women and infants, and as legal cases have begun to raise the question of fetal abuse, no professional group has come forward to serve as advocate for this special population of substance abusers. Meanwhile, however, physicians, nurses, social service agencies and public health officials have all been faced with increasing numbers of infants showing the detrimental effects of their mothers' drug use. Although problems of substance abuse in pregnancy have received increasing attention in the medical literature since the early 1970s, there has recently been a very rapid increase in the number of articles published related to this field. The reasons for this new interest are easily understood when current statistics from the National Institute on Drug Abuse are reviewed 1. Although patterns of abuse of alcohol, marijuana, heroin and other substances by women of childbearing age have changed very little over the last ten years, the incidence of cocaine use in this special population has been rising rapidly, a reflection of cocaine's increasing popularity among the general population of the United States.

Introduction to Mammalian Reproduction is a welcome contribution to the fields of gametogenesis, gamete transport, fertilization, and reproduction technologies. Key topics covered include:
*formation and maturation of male gametes;
*morphology and physiology of female gametes;
*how the sperm meets the egg;
*sperm-egg fusion, egg activation, and implantation of fertilized egg;
*assisted reproduction and environmental chemicals that have an effect on formation and function of male and female gametes. This book is for both researchers and students involved in reproductive biology.

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 field of human artificial reproductive technology (ART) is continually advancing and has witnessed significant changes since the inception of Louise Brown in 1978. Though Louise Brown herself was conceived after the trans fer of a blastocyst, there remain significant confusion and debate regarding the stage at which the human embryo conceived in the laboratory should be replaced in the mother. Developments in culture media formulations, leading to the introduction of sequential media, have brought the role of the blasto cyst in human ART back into the spotlight. It was due to this resurgence of interest in the niche of extended culture in human infertility treatment that the symposium on "ART and the Human Blastocyst" was held. of this meeting within this volume bring to the forefront The proceedings the main issues raised with the transfer of embryos at the blastocyst stage. It is evident from the chapters that follow that ART needs to be perceived as a continuum of procedures, each one dependent on the preceding one, and all equally as important as each other. That is to say, the development of a com petent embryo is ultimately dependent on the quality of the gametes from which it was derived. With regard to the oocyte, this then places the emphasis on the physician to use a stimulation protocol that both produces quality oocytes and does not impair endometrial function. Maintenance of gamete and embryo quality is the laboratory's role.

The Third International Copenhagen Symposium on Detection of Breast Cancer afforded a further opportunity for scientists from all over the world to come together and present important papers con cerning breast cancer and early diagnostic procedures. The Sympo sium was an opportunity to learn from extensive screening proce dures carried out at outstanding centers in the United States, Sweden, the Netherlands, and England. Furthermore, the Sympo sium dealt with new modalities such as ultrasonography, magnifi cation techniques, and magnetic resonance; and very important contributions concerning self-examination, fine needle aspiration biopsy, and radiation risks were presented. A whole section was also dedicated to the highly important cooperation between radiologist, surgeon, and pathologist. It is our sincere hope that a study of the different aspects of breast cancer presented in this volume will encourage the reader to join in the struggle against this dreadful dis ease. December 1986 S. Brunner B. Langfeldt Contents B. Nielsen Image Quality in Mammography: Physical and Technical Limitations . 1 S. A. Feig, B. M. Galkin, and H. D. Muir Clinical Considerations in Selection of Dedicated Mammography Units . . . . . . . . . . . . . . . . . . . . 15 . . . E. A. Sickles The Role of Magnification Technique in Modern Mammography . . . . . . . . . . . . . . . . . . . . . . . . . . 19 B. M. Galkin, S. A. Feig, P. Frasca, H. D. Muir, and R. Z. Soriano Imaging Capabilities and Dose Considerations of Different Mammographic Units . . . . . . . . . . . . . . . . . . 25 . . . E. A. Sickles Computed Tomography Scanning, Transillumination, and Magnetic Resonance Imaging of the Breast . . . . . . . . . . . 31 A. G. Haus Recent Trends in Screen-Film Mammography: Technical Factors and Radiation Dose . . . . . . . . . ."

The most meaningful reward to clinicians and researchers is the absence of recurrent malignancy in their patients. While in some patients the disease will be cured by resection alone, in other similarly staged cases the disease will recur despite adequate loco regional and systemic therapies. Hence, risk assessment is a complex issue with many related or unrelated prognostic factors determining outcome. The purpose of this volume is to review some of the most relevant prognostic factors of newly diagnosed breast cancer, focusing on fea tures determining the magnitude of risk. The ultimate value of establishing the significance of each prognostic factor in a given patient will be the resulting ability to plan individu alized therapies for patients at different risk of recurrence at the time of diagnosis. To secure the maximum benefit for high-risk patients, while avoiding undue toxicity in those with low-risk lesions, a well-integrated analysis of all known prognostic factors will be essential in the early postdiagnos tic period. In addition to well-established staging criteria such as axillary nodes, tumor size, receptors, scanning and radiographic examinations, the more sophisticated labora tory techniques, as discussed by several authors herein, will playa crucial role in risk assessment. Most of them, - ploidy determination, oncogenes, tumor markers, monoclonal anti bodies, growth factors, etc. -are presently available in only a minority of treatment centers.

The examination of the human fallopian tubes was, until recently, restricted to observations on gross anatomical disposition and tubal patency. These studies, for decades, were the domain of doctors and physiologists whose primary interest was population control and family planning, funded largely by organisations and agencies seek ing alternatives to steroidal contraceptives. For a "worrying" but short period after the birth of Louise Brown in 1978 as the conse quence of successful in-vitro fertilisation and embryo transfer, the fallopian tube was considered to be "dispensable" given that the metabolic milieu in which human fertilisation takes place could be effortlessly reproduced in a Petri dish, in in-vitro fertilisation procedures. However, a number of factors have acted together to renew in terest in the fallopian tube, namely new techniques in cell biology, microinstrument developments (in particular in imaging), an inter disciplinary transfer of skills from interventional radiology and car diology to gynaecology, the surgeon's wish to improve surgical tech niques, and better techniques to monitor early pregnancy. These factors have led surgeons to develop the new diagnostic and ther apeutic strategies and techniques listed here. This volume contains contributions from the majority of keynote speakers at a conference held in London in April 1992 from which its title is derived. Better diagnostic procedures should lead to the implementation of rational effective treatments.

The European School of Oncology came into existence to respond to a need for information, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons }Vhy such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidisciplinary approach which is difficult for the Universities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on future developments in specific fields of oncology.

Contraceptives have always provided ground for controversy. This book describes and discusses latest findings concerning the advantages as well as hazard and risk factors of contraception. The clinical impact of oral contraceptives on metabolism is particularly highlighted. In addition, behavioral methods, intrauterine devices, implants and modern approaches in animal and clinical research in the field of immunization against pregnancy are considered. Last, but not least, the book summarizes the complex ethical, religious and political aspects of family planning and contraception.

The Organon Symposia have actually become a tradition, keeping up with exciting developments in reproductive medicine. The purpose of this symposium on "Fertiliza tion of the Human Egg in Vitro" was to bring together the stilllimited number of elinical specialists in the field and to stimulate another group of basic research people to exchange their experiences and knowledge, hopefully promoting elose cooperation between the two groups. It was a kind of scientific "first" that all research teams so far successful in achieving the birth of a healthy baby, fertilized in vitro came together at a workshop conference without a large audience of spectators and reporters, but with a small number of highly critical colleagues from the fields of basic reproductive physiology and comparative developmental biology. This atmosphere allowed for the elose exchange of results, hypotheses, diagnostic and therapeutic procedures, criticism, and respect, and created very productive discussions, all of which furthered the aim of the method: To help more childless couples to have their own babies by the ultima ratio procedure of in vitro fertilization and embryo replacement. The book that has emerged from this symposium will help to disseminate the great amount of information and experience gathered among the scientifically and clinically interested colleagues of many other hospitals and universities who could not be invited to the meeting. At the same time, it will prove that there is much more work to be done in the basic and clinical sciences of human embryology and reproductive biology."

The many advances in breast cancer research, as well as the large quantity of published material, make it very difficult to gain insight into the global aspects of cancer management. To follow and understand all the new developments is becoming a major challenge. For this reason, the editors decided to bring together a group of top researchers in breast cancer to provide a comprehensive, yet readable conceptual review of the state of the art of breast cancer diagnosis and therapy. The proposal to focus the review on the quantitative assessment of the risk at diagnosis, the determination of which may permit selective therapies for individual patients, was met with enthusiastic approval, resulting in the present volume with contributions by the leading investigators in the field. While the volume relating to diagnosis, published re cently, focused on efforts leading to refinement at diagnosis of risk criteria sensitive enough to reliably distinguish the low- and high-risk categories, the second volume, by provid ing a review of the main problems and results of therapy given to high-risk patients, can be considered as a continua tion of the first book. A refined risk assessment at diagnosis and the application of the most suitable treatments to well selected individuals are the most important steps towards avoiding the present worrisome reality of overtreating the low risk and undertreating the high-risk patients. The first few chapters of the present volume offer an insight into the general management of early breast cancer.

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.