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 ultimate "consumer" of the data presented at conferences on the primary treatment of operable breast cancer is the patient, and when, as in this disease, the benefits of therapy are relatively mod est, the availability and interpretation of the data from trials be comes an issue of primary importance. The effects of present treat ment are in fact such that more patients relapse despite therapy than are estimated to benefit from it. It is, therefore, extremely dif ficult for the physician to recommend unequivocally one particular adjuvant treatment modality for the vast population of women with breast cancer. The interpretation of results from clinical research-oriented pro grams is constantly applied, however, in the treatment of breast cancer patients outside of clinical trials. From presented or publish ed data, many physicians extrapolate indications for the use of a given treatment regimen for their patients, perceiving it as the "best available therapy. " It is essential that the "best available therapy" be selected individually for each patient. However, considering the modest effect of treatment upon outcome, it is imperative that those who provide the data - those who are involved in both pa tient care and clinical research - make it known that the best cur rent treatment for the population of breast cancer patients is avail able within the framework of clinical trials. In this way not only present-day patients but also future ones will derive the greatest benefit.

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."

Endocrinologic investigations during pregnancy have focused in the last decades on placental hormones, the maternal endocrine system and maternal fetal interactions. Less is known about the fetus itself and the interaction of fetal hormonal response and physiological parameters. In this book physiologists, pediatricians and obstetricians active in experimental studies in both physiology and endocrinology combine both aspects of investigations. Historical remarks on the endocrine development of the fetus are followed by observations of the hormonal control of the cardiovascular system. Basic mechanisms of fetal endocrine control such as brain development, fetal growth, fetal behaviour, and thermoregulation are given particular consideration. Finally, carbohydrate metabolism and the mechanism of parturition are outlined.

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."

The account of "neonatal sterilization" is the story of the advocates of direct effect of steroids on the gonads and those who believed in the indirect influence, mediated through the hypothalamus and/or the pituitary gland. As often happens in biology, both convictions represent the same image seen from different perspectives. Prof DC Johnson (Kansas City, KS) reminisced the beginning of the story in a letter to me. I am paraphrasing parts of the letter with his permission. "As a starting point we could pick the life-long research of Emil Steinach ... " Steinach recognized the influence of testes on the develop ment of accessory sex organs in 1894, described virilization of females and feminization of males in 1913, and identified the controlling influence of the hypophysis on the gonads in 1928. He reviewed his work in a book Sex and Life, Forty Years of Biological and Medical Experience (E Steinach and L Loebe!; Faber and Faber, London, 1940). He got on the wrong road in later years and that is the reason everybody seems to have forgotten him. He presented his hypothesis that estrogen has a direct effect upon the testes, i. e. hormone antagonism, at the 1st International Congress on Sex Research in 1926.

The term polycystic ovary syndrome (peOS) is meant to describe a clinical endocrinopathy characterized by menstrual irregularity and evidence of hyperandrogenism. While recognized since the 1800s, a clinical composite was not constructed until 1935 when Stein and Leventhal reported their findings of seven women with infertility, menstrual dysfunction, hirsutism, and enlarged ovaries. Notably, the ovaries contained numerous multiple cysts and the ovarian capsule was thickened. At the time, this preciseness of definition was sufficient to entitle the entity Stein-Leventhal syndrome. Subsequently, over the intervening years as investigators attempted to un ravel the pathophysiology and genesis of this disorder and the number of reported studies increased, there ensued a gradual and distinct terminologic conversion to polycystic ovary syndrome, which, whether intentional or not, connoted a less well-defined condition. Perhaps this is appropriately so, given the seemingly broadening spectrum of clinical presentations and the continuing debate over what constitutes peos. The expansive new knowledge about peos was discussed to a significant degree at an international symposium organized by Serono Symposia USA and held in Boston in the late spring of 1995. Ovarian physiology, including the fate of the follicular unit, was a central focus with several presentations on the genesis, growth, and death of ovarian cellular components. A discus sion of the regulation of ovarian cell function was also highlighted and comprised a major portion of the program."

Sixty years ago, G. Fanconi published a paper entitled: "Familiiire infantile pemiziosaartige Aniimie (pemizioses Blutbild und Konstitu- tion)", in which he reported that this type of severe aplastic anemia represents a hereditary disease distinct from other pancytopenias of childhood (Fanconi 1927). Later this syndrome was named Fan- coni anemia (FA; van Leeuwen 1933). A more recent study of the genetics of FA confirmed that the syndrome is inherited in an au- tosomal recessive manner (Schroeder et al. 1976). Prenatal diagno- sis in FA families showed that about 25% of fetuses are affected (Auerbach et al. 1985, 1986). In 1964, Schroeder et al. discovered high frequencies of chro- mosomal aberrations in cultured peripheral blood lymphocytes from patients with FA. Schuler et al. (1969) reported that cells from FA patients are particularly sensitive to the chromosome-breaking activity or clastogenic effect of a polyfunctional alkylating agent. Since that time, studies of baseline and induced frequencies of chromosomal aberrations have been used for the identification of patients with FA. There is now a large body of data concerning the possible mechanism(s) underlying the hypersensitivity of FA cells to DNA cross-linking agents, the biochemical basis for which is still unknown. Complementation analysis, using cells from different FA pa- tients, has demonstrated genetic heterogeneity in the syndrome.

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.

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."

When presented with the task of editing a volume on such a wide When presented with the task of editing a volume on such a wide and and diverse diverse topic topic as as Ovarian Ovarian Pathology, Pathology, it it is is difficult difficult to to know know how how to to limit limit the the range range of of subjects subjects to to be be covered covered when when there there are are so so many many taxonomical taxonomical entities, entities, both both neoplastic neoplastic and and reactive reactive that that could could be be included. included. However, However, I I have have chosen chosen to to cover cover concepts concepts that that are are not not usually usually dealt dealt with with in in depth depth in in Gynaecological Gynaecological Pathology Pathology textbooks. textbooks. From From the the clinicopathological clinicopathological viewpoint, viewpoint, a a wealth wealth of of new new data data has has been been updated updated and and critically critically reappraised. reappraised.

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.

The number of studies on chronic and recurrent pain bears no relation to the frequency of these complaints in gynecologic practice, nor to the clinical and scientific problems that still need solving in this area. Several factors stand in the way of progress in this field, such as the strongly subjective nature of the complaints, the frequent lack of correlation between them and objective findings, and the complexity of the psychosomatic interac tions involved. Although progress in our knowledge has been much slower than we would have wished, and although we are well aware of these many gaps, it was considered useful to gather in a book what we think we have learned during 3 decades of active interest in pain patients and pain problems in gynecologic practice and 12 years of supervision of a pain clinic in the Department of Obstetrics and Gynecology of Leuven University. As there are many differences between acute pain - clinical as well as experi mental - on the one hand and chronic pain symptoms on the other, it was felt preferable to limit the scope of this book essentially to chronic and recurrent pain in gynecologic practice. When presented with a complaint of lower abdominal and/or low back pain, the gynecologist should constantly be on the lookout for nongynecologic causes, of which the most frequent will be either gastroenterologic or orthopedic and sometimes urologic. I have been fortunate in obtaining the collaboration of Dr."

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.

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."

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.

In the last decade of the 15th century a new and deadly disease called Morbus Gallicus, or syphilis, appeared and spread rapidly throughout Europe. The effects of syphilis were so severe that it, and those suffering from it, where regarded with horror and despair. It is difficult for the modern reader to appreciate the fog of confusion which surrounded sexually transmitted diseases in earlier times. Those suffering with these diseases were often condemned as victims of their own "sinful lust of the flesh"; a judgement attitude which hindered most of the early attempts at control and treatment. Despite this general attitude, there were some doctors who persevered in their attempts to understand the causes and discover treatments for syphilis and other sexually transmitted diseases. The Scars of Venus is illustrated with pictures of people, places, instruments and documents. It presents the historical background and achievements of the early venereologists through to the current venereologists' fight against HIV. This book will be of interest to anyone concerned with venereal diseases: doctors, nurses, counsellors, laboratory workers, medical historians, and those working in the areas of public/world health and the spread of infectious diseases.

During the past ten years numerous new findings have been documented in the field of gynecological pathology, especially in respect of neoplasms. These findings have been generated by the application of recently developed techniques of immunology and molecular biology. However, clinicopathologic examinations. are still an absolute requirement for the morphologic evaluation of neoplasms, including gynecological tumors. The International Society of Gynecological Pathologists (ISGYP) has contributed greatly to the progress within gynecological pathology. The ISGYP Nomenclature Committee has promoted the International Histological Classification of Gynecological Tumors under the auspices of the W orid Health Organization. A new edition of the classification of tumors and tumor-like conditions of trophoblastic disease, uterine corpus, cervix, vagina, and vulva is currently in press. A second volume covering the ovaries, fallopian tubes, broad ligament, and female peritoneum will be published later. Organization of scientific symposia and seminars has also been an important activity of the ISGYP. The present editor organized and chaired a symposium entitled "Recent Progress in Diagnostic Pathology of Gynecological Tumors" held in Sendai, Japan on 11 April 1986 in close cooperation with Prof. T. Okagaki, University of Minnesota Medical School, and under the joint auspices ofthe ISGYP and the Japanese Society of Pathology. The following topics were discussed at this symposium: - Immunocytochemistry of gestational trophoblastic disease (Dr. R.J."

Concise, recent data are presented on obstetric problems arising in patients with cardiovascular diseases (not only congenital and acquired valvular heart diseases and hypertension, but also uncommon heart lesions) and on cardiological complications encountered in pregnant women. The goal of the book is to provide obstetricians with necessary cardiological information and cardiologists with essential obstetric information to enable both specialists to make optimal decisions regarding the permissibility of pregnancy, management of pregnancy and labour, or termination of pregnancy, and selection of an adequate form of contraception in women with heart and vascular diseases. Along with recent scientific findings, the book contains practical recommendations for examination diagnosis and treatment that is effective for the mother and safe for the fetus.

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 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."