This book reviews the most recent developments in the patho- physiology and therapy of ventilatory failure. It contains contributions by twenty-five internationally recognized aut- horities on respiratory muscle function and investigators actively contributing to our knowledge of the cause, diagno- sis and therapy of ventilatory failure. Of particular inter- estare the descriptions of new modalities of partial and complete ventilatory assistance as well as new knowledge re- garding ventilatory control and fatigue during stressful breathing. The reader will find here a state-of-the-art re- view of the latest research and practical applications in this most critical area of intensive care medicine.

Besides the mortality rate the value of an operative procedure is measured against the incidence and the degree of undesirable postoperative sequelae. In the surgical treatment of gastroduo denal ulcerations vagotomy is now competing with the success fully established resection therapy. Since this latter method has been further developed during the last years and late results are rare, a comparison between both types of operation is difficult. Meritoriously, the authors have tried to perform a comprehensive analysis. Due to the complexity of postoperative syndromes the diagnostic procedure and treatment can be successful only after integrated cooperation by gastroenterologists and surgeons. This is documented by the current monograph which originates from a cooperation of several years and an active exchange of scientific will facilitate the indica and practical experience. The monograph tion for the primary surgical procedure by critical confrontation of the postoperative syndromes and provide advice in treating postoperative complaints. We hope that the monograph will have the expected impact, which means the spreading of the actual knowledge of post gastrectomy and postvagotomy syndromes.

Over the past ten years, carbon dioxide laser surgery has made impressive strides and is now applied to every field of surgery without exception. It is the intention of this book to record the work done in this field in the Department of Plastic and Maxillofacial Surgery of the Beilinson Medical Center and Tel Aviv University Medical School, Israel, as well as that performed in association with other depart ments. In this context, one feels that it is incumbent upon one to acknowledge the cooperation of the medical and paramedical staff of the Department of Plastic and Maxillofacial Surgery of the Beilinson Medical Center, as well as that of Prof. Yehuda Shindel and Dr. Daniel Katenelson of the Department of Ear, Nose and Throat, Dr. Y ona Tadir of the Department of Obstetrics and Gynecology and Dr. Itamar Kott of the Department of General Surgery. I should like to make special mention of Dr. Ralph Ger of New York, who worked with me on the original clinical trials, and the engineer Uzi Sharon, who developed the Sharplan Laser with me. The progress of Laser Surgery is well demonstrated by the participation in the four meetings of the International Society for Laser Surgery, the first of which was held in Tel Aviv in 1975 with an attendance of 65 and the last in Tokyo in 1981 with an attendance of 1200.

Controlled and predictable interference with hormonal feed- back mechanisms has become a major direction of preclinical and clinical research. There is a steadily increasing number of hormonal pep tides detected and characterized that are re- sponsible for endo-, para-, and autocrine cellular actions. Naturally, these peptides have been studied with regard to their cell growth stimulatory action and, in parallel, the re- spective antagonists are being investigated in terms of their antiproliferative (antineoplastic) function. Among the numerous pep tides of interest in this respect, somatostatin (somatotropin release inhibitory factor) and bombesin antagonizing factors have been the topic of inten- sive research during recent years. No presentation of the role of pep tides in oncology would be complete without a compre- hensive treatise of their physiological, preclinical and clinical functions in the context of their antineoplastic mechanism of action. Somatostatin and its various short- and long-acting analogs have the unique feature of suppressing and inhibiting a wide range of cellular processes including cell proliferation. Recep- tors for these peptides, which belong in a wider sense to the family of neuropeptides or neurotransmitters, are widely dis- tributed, a feature which is not in keeping with the general view of a growth hormone regulatory system. Thus, these substances are found in the gut in a variety of endocrine and exocrine glands including breast, pancreas, and prostate, and in the nervous system.

One out of every two men over eigthy suffers from carcinoma of the prostate.It is discovered incidentally in many patients with an alleged benign prostatic hyperplasia. In treating patients, the authors make clear that primary radical prostatectomy is preferred over transurethral resection due to the lower complication rate.

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.

Rapid developments in this successful diagnostic and operative technique have called for a new edition of "Arthroscopy of the Knee Joint." This second edition has been completely revised and retains very little material from the first edition. The diagnostic section has been considerably expanded and elucidated and the operative section adapted to modern technology. The first part of the book presents the external conditions and pre-requisites for diagnostic arthroscopy. The endoscopic anatomy and pathology of the knee joint are covered in detail. Particular emphasis is placed on practical hints for accurate arthroscopic procedures. The second part then discusses operative techniques. The reader discovers step-by-step how and which pathological findings should, in the author's opinion, be treated. Here, too, the problems and possible complications of arthroscopic surgery relevant to the individual techniques are dealt with in detail. Equipped with this book, the reader will be thoroughly informed on all current arthroscopic methods and possibilities.

Inflammatory dieseases of the pancreas occur with increasing incidence in western industrialized countries. This volume deals with all aspects of CHRONIC PANCREATITIS including epidemiology, etiology, morphology and pathophysiology, dia- gnostic imaging as well as conservative and operative treat- ment. Very recent data based on experimental and clinical research projects are presented. The contributions have all been written by a team of internationally well recognized authorities in the various fields involved. Topics of parti- cular interest include feed-back regulation, new aspects of conservative and interventional treatment as well as modern surgical approaches including organ-preserving procedures.

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).

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."

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 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."

This work is derived from the International Symposium on Advanced Laparo-Endoscopic Surgery, reknowned for being a comprehensive program that brings together international leaders in the field to discuss the current state of practice, the emerging possibilities and the future directions for research. The program focuses on the experiences in large series which have set the standard of practice and won acceptance for laparo-endoscopic surgery in recent years; the panelists and lecturers span the field from concept to realization. The program also addresses the evaluation process by which innovations should be judged in the interest of safety, clinical efficacy and cost effectiveness to improve the delivery of surgical care in the world. The symposium clebrates the firm establishment of laparo-endoscopic surgery and the promise of the future. Together, members of the panel outline future innovations that will change the practice of laparoscopic surgery, showcasing the future of robotics, virtual reality, telesurgery, needlescopic surgery, minimally-invasive breast surgery, cryotherapy and live donor nephrectomy.Highlights include contributions by John Hunter (Endo-Gastric Surgery), Dana Anderson (Repair Common Bile Duct Injury), Jack Jackimowicz (European Laparoscopic Hernia Multi-Institutional Study), Alfred Cuschieri and John Flowers (Role of Clinical Trial for New Procedures).

Gastric cancer has been one of the great malignant scourges affecting man kind for as long as medical records have been kept. Until operative resection pioneered by Bilroth and others became available, no effective treatment was feasible and death from cancer was virtually inevitable. Even with resection by total gastrectomy, the chances of tumor eradication remained small. Over recent years, however, the situation has been changing. Some changes have resulted from better understanding of the disease, early detec tion, and better management techniques with applied clinical research, but the reasons for other changes are poorly understood. For example, the incidence of gastric cancer is decreasing, especially in westernized societies, where it has fallen from one of the most common cancers to no longer being in the top five causes of cancer death. Still it remains the number one killer of adult males in Japan and Korea. Whether the reduced incidence in western societies is a result of dietary changes or methods of food preservation, or some other reason, is as yet uncertain. Improvements in outcome have been reported from mass screening and early detection; more refined techniques of establishing early diagnosis, tumor type, and tumor extent; more radical surgical resection; and resection at earlier stages of disease."

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.

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 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.

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

It 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.

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 . . ."

In contrast to the continuously increasing success in kidney, liver, heart, and pancreas transplantation, small-bowel transplantation has not shown simi larly impressive progress until recently. The few clinical attempts at small-intestinal transplantation in the late 1960s and early 1970s were unsuccessful. In spite of these initial failures, a few groups of surgeons continued to investigate the problems of small-bowel transplantation from the technical, functional, and immunologic point of view. Now, about 15 years later, conditions have changed. Total parenteral nutrition has made tremendous progress, thus maintaining patients with short-bowel syndrome who are potential recipients of small-bowel grafts in an acceptable physical condition. Immunologists and clinicians have furt hermore been able to expand our knowledge of basic immunologic reactions induced by transplanted organs. In addition, within the last 8 years, new immunosuppressive drugs and regimens have been introduced which have proved to be extremely effective. Taking all these aspects into account, we regarded it as an extremely worthwhile and effective undertaking to invite scientists from all over the world who are working in the field of small-bowel transplantation to participate in a symposium on this topic. This meeting, the first to deal exclusively with small-bowel transplantation, was held in Kiel, West Ger many, in October 1985. Its aims were twofold: 1. ) To'stimulate direct communication between basic scientists and clini cians 2."

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.