It is now more than 40 years since Drs. Wild and Reid published their first experience with rectal ultrasonography from the Surgery Department at the University of Minnesota. Professor Owen H. Wangen steen, in whose laboratory the studies were carried out, recognized at that time the need for early detection in the treatment of cancer. Technical improvements over the past 20 years have made endoscopy the procedure of choice for examination of the hollow organs of the genital, urinary and gastrointestinal tracts. The simultaneous development of endosonography has had an equally dramatic impact on the practice of medicine and surgery. The technology has been demonstrated to be helpful in both benign and malignant conditions. One of the so-called benign conditions of the anorectum is fistula-in-ano. Fistula surgery has always relied on excellent anatomic delineation of the intramuscular tracts. There is hope that adaptation of ultrasonographic technology will aid in the surgical management of this malady. Clearly, rectal ultrasonography has considerable potential in the management of rectal carcinoma. Accuracy rates in the range of 90% for the depth of neoplastic invasion have been reported. This ability for accurate assessment will undoubtedly lead to a better definition of the population of patients that can be managed by local therapeutic means.

Modern surgical oncology is characterized by multimodal therapy. In recent years numerous therapeutic approaches of pre-, peri-, intra-and postoperative treatment have been in vestigated with regard to their use in combination with surgi cal intervention. It now is time to analyze and to define the state of our knowledge. For tumors of the gastrointestinal tract there are several encouraging therapeutic approaches, such as preop erative chemotherapy in esophageal and perioperative chemotherapy in colon cancer. For some special tumors, like anal carcinoma, we have clearly defined combined therapies which even now must be viewed as standard treatment. It is also time to demonstrate the results of several clini cal studies that have been conducted within the last few years that combined surgical efforts with pre- or postinter ventional chemotherapy or radiotherapy. It is necessary to evaluate whether these trials contribute to progress in onco logical therapy. The editors of this volume - surgeons at the university hospitals of Heidelberg and Zurich - must be given the mer it of achieving these goals. It was especially appropriate for the Department of Surgery in Heidelberg, in close coopera tion with the Comprehensive Cancer Center Heidelberg/ Mannheim, to prepare a review of our present knowledge of surgical oncology as it is in the tradition of attempting to combine different therapeutic approaches to cancer therapy.

Main focus of the new book will be the description and discussion of rat and mouse models for organ transplantation. Various microsurgical techniques will be presented which allow transplantation of functional organs in syngeneic systems. In particular, the extremely difficult methods necessary for organ transplantation in mice will be presented and evaluated. Besides these practical aspects the book will also cover the theoretical sides of organ transplantation like the immunobiology of allotransplantation. Special emphasis will be given to the resurgent field of xenotransplantation. The results from xenograft models developed in the recent years using rats or mice will be reviewed and their impact on future human xenotransplantation will be discussed.

For the first time four crucial aspects of gastrointestinal endoscopy are combined in a single text. Drugs for sedation and monitoring of the patient are addressed with particular reference to safety issues and comfort and acceptability for the patient. Resource management and health economic techniques are applied to endoscopy to determine quality and outcome. Problems of negligence and informed consent form the basis of a medico-legal examination of endoscopic practices.

Since the small bowel except the duodenum and (1961), Pygott et al. (1960), Gianturco (1967) terminal ileum is largely inaccessible during en- and Bilbao et al. (1967). doscopic examination, radiology of the small Sellink, however, was really responsible for bowel attains special significance as a diagnostic the widespread recognition of enteroclysis method. Owing to the length and position of (1971, 1974, 1976). In spite of the increasing this organ, good images are difficult to obtain. popularity of this method, the necessity for sub- Furthermore, the considerable variation oftran- stituting this apparently viable method for the sit time, unpredictable response of the contrast peroral examination is still equivocal (Rabe medium, and superimposition with the filled etal. 1981; Fried etal. 1981; Maglinte etal. loops make small bowel radiology difficult. As 1982; Ott et al. 1985). Comparisons of both methods, however, (Fleckenstein and Pedersen a result, few radiologists specialize in this field. With the exception of Crohn's disease, disorders 1975; Sanders and Ho 1976; Ekberg 1977; Val- lance 1980) have confirmed the superiority of of the small bowel are relatively rare. Thus, not many clinicians and radiologists are interested enteroclysis. It achieves a high accuracy (Antes in the small intestine. and Lissner 1983).

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 why such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidiscipli nary 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 on cology."

The European School of Oncology came into existence to respond to a need for informa tion, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons why such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidisciplinary approach wh ich is difficult for the Univer sities 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, monocional 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 use oflasers in clinical practice is increasing rapidly, both in the definitive treatment of disease and in the palliation of symp toms. Consequently, this sixth contribution to the Bloomsbury Series in Clinical Science is particularly timely. It opens with an introduction to the basic physics of lasers and then focuses on the current use of lasers in urological practice, and concludes by reflecting on their potential for the future. Edited, and with several contributions by Tom McNicholas, the book also contains contributions from a number of workers at the National Medical Laser Centre in University College Hos pital. London. Given their ever widening application, there can be little doubt that lasers will be a subject the series will return to again. To date, the series has been concerned with a wide range of topics of fundamental importance in clinical science. It has now gained momentum and future titles continue to reflect its wide sphere of interest. As Series Editor, I would welcome suggestions from readers of topics and issues that could usefully be addressed in the series.

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.

The regenerative capacity of the liver cell is almost unlimited. Therefore after acute liver damage, be it viral, toxic, hypoxic, or surgical in origin, restitutio ad integrum is the usual outcome. In two forms of liver disease, however, this is not the case: in fulmi nant hepatic failure, liver regeneration often is not fast enough to keep the organism alive; in end-stage cirrhosis, regeneration is dis turbed by a hypertrophic architecture of fibrotic tissue. For these extreme forms of liver disease and for critical situations before and after liver surgery, artificial liver support is needed. This book contains the latest results in this area of research pre sented by scientists from allover the world at an international symposium held in Celle, Germany, June 2-4, 1980. Exciting new methods like continuous membrane plasma sepa ration and liver cell transplantation into the spleen have been de veloped. The older methods of hemoperfusion and dialysis have been improved. Enzymological methods and liver transplantation have made good progress. We hope that this volume will help the clinician in his decision-making and stimulate ingenious new re search for the benefit of our liver patients."

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."

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 roentgenologic visualization of excretory ducts of a secreting organ is a longe-stablished diagnostic method in roentgenology. For a long time, radiologists have felt the need to establish a method for filling the excretory duct system of the pancreas with contrast material, in the way that intravenous retrograde urography is used to diagnose pathologic changes such as displacement of the renal collecting system or of the urethra. This need to establish a method became more urgent the more the pancreas resisted conventional roentgenologic clinical di- agnostic methods. From time to time in peroperative or postoperative cholangiography mostly incomplete reflux into the pancreatic duct in 10-14% was observed (Stiller, 1948; San Julian und Pascual y Megias, 1952; Wapshaw, 1955; Bergkvist und Seldinger, 1957). However, there was no possibility of obtaining reliable and complete opacification of the pancreatic duct. Peroperative Pancreaticography It was in 1951 when Leger and Arway achieved this goal, though only by surgery. It should be mentioned that, when performing their first peroperative examination, these French surgeons already had the impression, that cannulation of the pancreatic duct was easier than cannulation of the common bile duct. This observation has been con- firmed by hundreds of examinations after ERPC had been established for several years; however, up till now this phenomenon has not been sufficiently explained. During the following years, peroperative pancreaticography develop- ed into a routine examination, above all by Doubilet et al.

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 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 why such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidiscipli nary 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 on cology.

Primary and metastasizing malignant carcinoma of the liv er represent a challenge to both the diagnostician and the therapist. For this reason, it appears a worthwhile task to review the current status of knowledge about the treatment of primary and metastasizing tumors of the liver. The ques tion is whether modem diagnostic methods and new thera peutic concepts can help to improve the prospects of treat ment. Of particular interest is the role played by therapeu tic procedures directly involving the liver. Thus, it is equally important to discuss the pathophysiological and pharmacological bases for a modem therapy concept as it is to consider diagnostic issues and possible definitions of stages of progression. Therapeutic concepts comprise sys temic therapy and organ-related therapeutic methods, in cluding surgical resection, changes in the blood supply, re gional selective chemotherapy, and other localized or regional, highly specialized forms of therapy. This survey of the various possibilities in the field is meant too to stimulate further scientific research, given that methods of treatment are as yet by no means stan dardized, but are still in the stage of clinical research, where experimental models can find an application. The only well-established operative procedure is surgery on the isolated liver tumor. In this area, specialized techniques and various intraoperative procedures are discussed. There is a wealth of information available on all the top ics covered."

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.

A thorough knowledge of normal radiological anatomy is necessary for detection and evaluation of pathological changes. In pediatric radiology, normal anatomy and normal proportions of anatomical structures may differ considerably from the adult, and may vary during growth. Therefore, in pediatric radiology there is a multitude of measurements, that in the individual patient is important, but that for the radiologist is not meaningful or even possible to keep in mind. This holds true both for the experienced pediatric radiologist, and for those who practise pediatric radiology only occasionally. This volume is written for both categories. In the literature, normal values are calculated and presented in many different ways, that are not always easy to compare, or easy to use in daily work. Therefore, we have revised and recalculated the data given by authors, in order to present the statistical upper and lower normal limits as between plus and minus two standard deviations (+/- 2SD). This means that about 2% of a normal population will be assessed as abnormally large and around 2% abnormally small with respect to the parameter assessed. In this way, the presentation throughout the book is uniform, and hopefully easy to use. All figures have been redrawn and computed in an attempt to make them as clear as possible.

At first sight it may appear strange that a volume of Progress in Pediatric Surgery should be devoted to the history of our specialty. One assumes that progress is concerned primarily with recent developments whilst history deals with matters of the past. However, in the past there has also been considerable progress in the development of our understand ing of paediatric surgical problems, otherwise we would not have pro gressed to our present achievements. The editors, therefore, do not apologize for compiling this volume but, on the contrary, feel that the publication of this volume is most timely. Modern paediatric surgery has now been practised for three genera tions. The handful of pioneers who were the founders of our specialty worked mainly before the last world war. A few dozen of the inter mediary generation started work immediately after the war, while the new generation who are now dominating our specialty must be counted in thousands. Two factors have radically altered paediatric surgery as practised by the intermediary and the present generation of surgeons."

A workshop was organised in order to achieve multi-discipli- nary review of the pathogenesis and management of acute failure, particularly as it occurs and is managed in intensive therapy units. The book deals with the realities and practicalities of this important area of acute medicine. Each chapter is followed by a discussion, so that a concen- sus view is obtained from an international body of experts.

In 1968 the first contacts were arranged with the publishing house of Urban & Schwarzenberg concerning the establishment of a periodical to be produced in English with the aim of publishing important scientific work in pediatric surgery and related disciplines. I thought especially of certain excellent inaugural disser tations and theses. When Urban & Schwarzenberg promised to start such a series, I recruited Peter Rickham, then in Liverpool and now in Zurich, and Jean Prevot of Nancy as executive editors. We chose the title Progress in Pediatric Surgery - Fortschritte del' Kinderchirurgie - Acquisitions en Chirurgie Enfantile as the name of our new series. The first volume was published in 1970, followed by another 16 volumes during the next 14 years. At the suggestion of Michael Urban, we turned from the publication of long papers to theme-based volumes, which proved to be extraordinarily useful. Mr. Urban, the head of Urban & Schwarzenberg, told us in 1982 that his firm could no longer look after Progress in Pediatric Surgery. With the agreement of Mr. Urban, we had to look for another' publisher and found Springer-Verlag, who agreed to continue publishing Progress in Pediatric Surgery in the approved lay-out. We cordially thank Dietrich G6tze of Springer-Verlag for his helpful support. This volume (No. 18) is the first of Progress in Pediatric Surgery to appear under the guidance of Springer-Verlag. We want to express our thanks to Mr. Urban and Dr."

Technical improvements over the past twenty years have made endos copy the procedure of choice for examination of the hollow organs of the genitourinary and gastrointestinal tracts. The development of electro surgical techniques, laser technology, injection therapy, and a wide variety of other modalities now allow the endoscopist to treat many problems that in the past required open surgery. The simultaneous development of transcutaneous abdominal sonography has had an equally dramatic impact on the practice of gastrointestinal and geni tourinary surgery. The marriage of these proven technologies, known as endoscopic sonography, provides an exciting new modality that promises to further revolutionize the diagnosis and management of many intraabdominal diseases. Endoscopic sonography opens new frontiers by overcoming the primary limitations of its parent technologies. Fiberoptic endoscopy is limited by the inability to see beyond the luminal surface, this is particularly important when considering neoplastic disease because depth of wall invasion is a key factor in determining treatment. The limiting factor in transcutaneous sonography is the distance between the transducer and the target organ. With endoscopic sonography, the transducer is placed in close proximity to the target organ. This allows the use of high frequency waves (greater than 5 MHz), which provide better tissue resolution and eliminates the image distortion caused by overlying structures.

If a consecutive series of patients with lung cancer is followed up until the decision is made about therapy, it emerges that the role of surgery is quite small. Only a very limited proportion will ultimate ly qualify for rationally conceived surgical therapy; most patients are inoperable. In a series of 397 patients investigated at our hospi tal, 78% were inoperable on the basis of preoperative evaluation and a further 3% proved nonresectable at thoracotomy; therefore, only 19% were suitable for resection. On the other hand, surgery is still thought to offer the best, if not the only realistic chance of cure. The question "operable or not?" is therefore of vital importance for the individual patient. The answer to this crucial question must be based on valid guidelines for pa tient selection and preoperative evaluation, and it should be clearly defined what extent of resection is necessary in order to realize any curative intention. In 1972 a thorough analysis of the literature revealed that re section of bronchial carcinoma - although 40 years old - was being undertaken with very variable indications. There was hardly any systematic staging, and assessment of results was hampered by the fact that most communications in the literature were based on retrospective analysis.

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 . . ."