In the last decade, physicians have witnessed a publication will serve as a stimulus to surgeons growing awareness of and concern with diseases of concerned with male reproductive disorders to in the male reproductive tract. Stimulated by this tensify their personal research attempts to develop interest, a refinement and re-evaluation of existing better therapy for diseases referable to the male reproductive system. It is finally hoped that this surgical techniques for treatment of male repro ductive disorders has been concurrently appreci publication will stimulate critical analysis of what ated. Rapid progress in this area has resulted we feel are currently accepted surgical modes of primarily from a cooperative effort from those therapy and to better promote a general inter specialists in the areas of microsurgery, medical change of clinical information referable to these and surgical oncology, endocrinology and neuro disorders. physiology, pathology, immunology, genetics and Those who have provided the text and illustra biochemistry. tions for this volume have contributed a significant As the surgical treatment of diseases and ab amount of work, and we hope that they feel their normalities of the male reproductive system has material has been well used. The editors also wish to expanded, so have the articles describing these often thank Mr."

Sepsis is still the leading cause of death in surgical and general intensive care units. Although our knowledge of this complex syndrome has increased in recent years, it is still far from com- plete. New therapeutic approaches have been developed. Some did not fullfill the high expectations for their use in clinical prac- tice; others are still under clinical evaluation. is the aim of this monograph to offer basic information on the It etiology, definition, pathophysiology, prevention and therapy of sepsis and septic shock to both the clinician and the scientist. We believe that it presents an extensive overview that may help the clinician to better understand and treat sepsis and septic shock. We also hope that this work will give some directions for future research both in the clinical field as well as the laboratory. Jena, Berlin, Jerusalem, K.Reinhart February 1994 K.Eyrich C.Sprung TableofContents I.Definition/Prognosis Sepsis and Septic Shock: Update on Definitions (Jo-L.Vincent) 0 0 0 0 0 0 0 0 0 0 0 0 ******** 3 Clinical Manifestations and Prognostic Indicators in Sepsis (R.C.Bone) ...0 * * * * * * * * * * * * * * * * * * * 16 What Determines Prognosis in Sepsis? Evidence for a Comprehensive Individual Patient Risk Assessment Approach to the Design and Analysis of Clinical Trials (W.A.Knaus, D.P.Wagner, F.E.Harrell, Jr.

How to treat advanced prostatic cancer remains controversial, despite intense basic and clinical research investigating the pathogenesis and natural history of this unique cancer highly prevalent in elderly males. Nine experts were asked to meet and discuss the facts. This resulting monograph gives an overview of the available knowledge on all aspects of the subject. The objective evaluation and consensus opinion of the authors presented here set this book apart from other publications with conflicting viewpoints. For readers eager to obtain a comprehensive and balanced view of the thousands of clinical contributions and clear advice on the choices, this book is a must.

In the past two decades, considerable interest in skin cancer has developed in the public and scientific communities. There may have been several reasons for this: - The rise in the global incidence of cutaneous cancers - New molecular biology techniques resulting in a better understanding of pathogenesis and improved diagnostic procedures - The advent of new pathological entities, e. g. , the endemic form of Kaposi's sarcoma - A constantly increasing range of therapeutic modalities, providing even more efficacious treatment and manage ment of skin cancers As N. E. Fusenig describes in the first chapter of this volume, basic research is only beginning to unravel the complex mechanism involved in cellular dedifferentiation and tumor progression. Progress is dearly needed, especially in dermato oncology, where the rise in the incidence of epithelial tumors has inflated the overall skin cancer incidence. The incidence of tumors of the skin exceeds that of all other neoplasias in humans, with recreational sun exposure being a suspected primary cause. Several studies on the effects of UV radiation have been included at the beginning of this volume. Even the role of long wavelength UV (UVA) has become a focus of research activities. The main concern is that the low carcinogenicity of UVA, in comparison to UVB, may be outweighed and exceeded in its effects by increased UV A exposure, e. g.

The only book to attempt any perspective on methods of assessing cell proliferation is published to satisfy the growing interest amongst pathologists and clinicians in areas which have for more than three decades been the preserve of experimental biologists

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 which 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, 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.

In the last 10 years, total prosthetic replacement has become the hip oper ation for many but not all surgeons. In our clinic the increasing frequency of TP has been paralleled by a reduction in the frequency of 10 and HA. For the experienced orthopaedic surgeon and hip surgeon, hip disease has so many facets that it could not possibly be tackled with one operation alone. Thus, HA seems recently to have won renewed recognition. It has once more become the procedure of choice in specific cases, possibly because of certain disadvantages and complications associated with TP which have somewhat tempered the original optimism. Currently, the risk of infection or loosening of the pros thesis is such that the operation cannot justifiably be recommended for patients under 55-60 years of age. In contrast with HA, in the majority of cases the results of TP or 10 are not fully predictable. The loss of joint motion is offset by two important advantages: -complete freedom from pain - full weight bearing is possible on the arthrodesed hip. On following up our HA operations from 1961 to 1971, we examined the development of the operative procedures in our clinic. We found that the range of indications had narrowed as stricter criteria were applied in choosing patients for operation. Adequate and precise operative tech niques were developed. We studied the biomechanics of the hip joint exten sively (effect of arthrodesis on the statics and dynamics of the hip joint and neighbouring joints).

Investigation of anorectal disorders has become a very wide field reaching from case history and simple plain radiography to advanced techniques such as defecography, nuclear medicine, endosonography, computed tomography, and magnetic resonance imaging. The place and value of defecography, thedynamic demonstration of bowel evacuation, have not previously been clearly defined. In this highly illustrated volume, radiologists experienced in thisfield describe techniques, radiation risks, and the interpretation of normal and abnormal findings using the aforementioned techniques of investigation. Anorectal surgeons and gastro- enterologists also participatein the discussion of indications and the influence of abnormal findings on patient management. This book will be helpful as a practical guide tothe choice, performance, and interpretation of the appropriate investigationfor a patient with functional anorectal disorders. As such it represents an excellent addition to the library of every physician and specialist withan interest in anorectal disease.

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.

Since surgery became a method of treating patients, progress in the field has been intimately associated with experimentation and serendipitous research. As in other clinical specialties advances in surgery can be considered to result from experimental attempts to increase basic knowledge and to improve technical skills. However, virtually in no other area do concepts and approaches of experimental research enter clinical routine as fast as in surgery. There are numerous examples of this. Thus, allocation of manpower and resources for surgical research can be considered particu- 1arly profitable as convincingly shown, for instance, in renal transplantation by comparison of the long-term burden of hemodialysis vs. kidney grafting, apart from the relief of suffering and misery. Surgery is a continuously spreading field, and so is surgical research. This volume is a case in point. Its spectrum reaches from basic molecular biological aspects of immune mechanisms to the current state of the art of pulmonary surgery of cancer metastases, and from the molecular processes of cell swelling in ischemic brain edema and blood-brain barrier damage to novel forms of resuscitation or of treatment of insulin-dependent diabetes mellitus. Surgical research faithfully reflects a constant reorientation of medical disciplines. Treatment of renal or gallbladder concrements was a major domain of surgery, where the introduction of extracorporeal shock wave treatment now supplies noninvasive, virtually conservative alternatives.

This book is dedicated to the memory of Walter Brendel, late Professor of Experimental Surgery and Chairman of the Institute for Surgical Research at the University of Munich, Germany. For 20 years Walter Brendel organized the renowned Round Table Symposium on Applied Immunology, first in Kitzbiihel and later in Axams, Austria. On the occasion of the 20th symposium in January 1989 he gathered together a number of scientists who have been leaders in the field of transplantation immunology and clinical transplantation for the past two decades. All of them had participated at previous meetings, some on a regular basis. Many of the new discoveries in applied immunology and transplantation medicine were first presented and vividly dis cussed at the Round Table Symposia. The annual Kitzbiihel! Axams meetings became well-known and invitations much sought after, not only for this reason but also because of the uniquely intimate atmosphere that promoted the free exchange of research findings and theoretical cut and thrust.

Tumours in Urology is an up-to-date review of the advances in clinical management, clinical science, and basic science aspects of urological oncology. The text is divided into four parts for ease of reference: In these sections the molecular biology and biochemistry of bladder cancer, prostate cancer, and renal cell cancer are examined. There are authoritative reviews of the risk factors in superficial bladder cancer, the role of chemotherapy and bladder reconstruction in invasive cancer, along with comparative views of conservative treatment and the role of radical surgery in prostate cancer. Current methods of hormonal manipulation are also discussed. Conservative surgery for renal cancer, the use of interleukins, and the use of radical lymphadenectomy for testis cancer are comprehensively set out for the reader. A unique feature is the review at the beginning of each section of the controversial areas within each major topic. This gives the reader an excellent overview of recent advances in the field.

Present knowledge in regional cancer therapy is presented in this volume. The latest research addresses the questions of optimal drug development, the best galenic form and schedule to control tissue distribution at the tumor site and efficient treatment of specific anatomical regions.

Sepsis and Innovative Treatment: The Odyssey R. C. Bone The Odyssey by Homer, dates back to the 8th century, B. C. [1]. It is a great epic adventure of Odysseus's dramatic journey from Troy back home to Ithaca. Odysseus survives the ordeals of this journey and returns with new powers and insights. The study of the pathogenesis and treatment of sepsis has also been an odys- sey. I feel we will return from this odyssey with new insights and treatments. However, as with Odysseus, this will occur only after considerable struggle. In the 1980s we had a rather simplistic view of sepsis. It was a highly lethal complication caused by infection and often charac- terized by shock and multi-organ failure. Our knowledge of the inflammatory responses associated with sepsis was embryonic compared to today. The inflammatory response was often treat- ment with mega-dose corticosteroids along with fluid resuscita- tion, vasopressors and antibiotics. Because of the paucity of mul- ti-center controlled trials documenting the risk/benefit ratio of the treatment of sepsis with corticosteroids, two large multi-cen- ter controlled trials were organized to evaluate the role of corti- costeroids in sepsis [2, 3]. Because animal models showed bene- fits of corticosteroids only with pre-treatment or early treatment, a definition of sepsis was used that did not require positive cul- ture documentation or septic shock to be included in the studied population.

The introduction of computed tomography in the diagnosis of pathological intracranial conditions has had considerable significance in cases of cranio cerebral injury. The decisive diagnostic advantage lies in the possibility of demonstrating both gross pathological change directly as well as secondary changes in normal brain structures. Computed tomography has proved its considerable worth, especially in evaluation of patients with craniocerebral injury and its sequelae. The capabilities of CT were quickly recognized and use of the technique spread rapidly. It is likely that CT will be available within a few years in all hospitals and clinics treating patients with craniocerebral injury. We believe it appropriate to present a detailed report on our experience with CT in 1800 cases of craniocerebral injury treated in the neurosurgical departments in Miinchen-GroBhadern and Berlin-Charlottenburg over a period of five years. Both acute posttraumatic complications and late sequelae are discussed extensively. A large number of illustrations is provided in order to facilitate the reader's introduction to CT diagnosis. The great interest in our conjoint study originally published in the German language, induced us to translate this book and to update the clinical material. We wish to thank the Stiftung Volkswagenwerk, the Senat of Berlin, the Ludwig-Maximilians-Universitat in Munich and the Freie Universitat of Berlin for the generous financial support which made this study possible."

There has been great progress in ureteral surgery in the last twenty years. The predominant indication is still calculous obstruction but reparative and plastic surgery of the ureter for congenital and acquired lesions are among the most interesting advances in modern urology. The essential goal of this surgery is to ensure free flow of the urine from the kidney to the bladder and so to preserve or improve kidney function which is always affected or threatened by any defect in the excretory pathway. The ideal is to re-establish a closed circuit flow from kidney to bladder by repair or substitution of the ureteral conduit so as to avoid as far as possible the dis abilities that result from diversion of the urine to the skin surface or to the intestine. This objective can now be achieved in the treatment of most of the diseases of the ureter when the relevant kidney is sufficiently healthy to merit conserva tion. The techniques used are not necessarily new but the advent of antibiotics has made it possible to avoid or reduce the risks of infection, pyelonephritis, or pyonephrosis that so often complicated such surgery in earlier times. Progress in the investigation of renal function and of the excretory tract has brought a better understanding of the physio-pathology of the urinary apparatus and more accurate judgement of the results of reparative surgery."

The editorial group has selected these papers for publication in Progress in Orthopaedic Surgery from contributions to the "Reisensburg Workshop of Clinical Trauma Surgery" dealing with the lesions of knee ligaments and cartilage in 1975. They represent a survey of today's knowledge of pathophy siology, diagnostic means, and therapy of these lesions in the German-speaking countries. There are two "Reisensburg Workshops" annually, covering current topics of traumatology sponsored by the Ulm trauma group. Primary attention is focused not upon review lectures but rather upon the extensive discussions thus resulting in recommendations to the practising trauma surgeon in order to facilitate his clinical work. Ulm, November 1977 C. Burri, A. Ruter Introduction This volume of Progress in Orthopaedic Surgery presents a selection of papers dealing with injuries to the ligament support and articular surfaces of the knee. The menisci are not discussed as separate entities, but rather in their correct perspective as part of the knee jointsupport mechanism. As the editor for this volume, I have tried to select the most representative articles which cover this subject. These are publications from our European colleagues and reflect their opinion and experience. I have tried not to change their content or meaning in any way. This volume has been divided into six basic segments. Each deserves comment."

Implantable jOint prostheses which have been under development for more than 25 years, are today being used with success in the rehabilitation of many cases, including patients with extremely severe joint pathology. However, artificial joint designs still pose problems with respect to their function, anchoring, materials employed and the interaction of the prosthesis with the surrounding biological tissues. Some of these problems are associated with considerable therapeutic complications. Further improvement in the artificial joint requires the application of all the modern experimental and research techniques and the close cooperation of medical doctors, engineers and scientists. The International Symposium on Advances in Artificial Hip and Knee Joint Technology held at Erlangen on October 30 and 31, 1975 under the auspices of the Societas Physica Medica Erlangensis, had as its aim the promotion of just this interdisciplinary cooperation. One of the traditional objectives of the Societas has been the advancement of diagnosis and therapy by the adaptation of medical skill to modern technology and scientific engineering concepts. The major objective of this volume is to present, in expanded form, the lectures given by internationally recognized scientists and clinical researchers in the field of artificial joints in the locomotor system, and to make that information available to a wider public. The experience discussed covers the principles and primary methods of joint replacement.

The use of the compressed air-driven turbine for the activation of surgical burs and saws as developed by Dr. Robert M. Hall has been a boon for the plastic, max illofacial, and oral surgeon. The development of air instrument surgery coincided with the opening of new vistas in surgery in the area of craniofacial surgery. Cranio facial osteotomies for orbital (ocular) hypertelorism, for the deformities of cranio stenosis (Cronzon's disease, Apert's syndrome) and subcranial osteotomies at various levels of the facial skeleton have brought about dramatic improvements in the form of the facial substructure in patients with gross deformities. In many of these maxillofacial deformities the facial skeleton and dento-alveolar processes must be advanced, recessed or expanded in the lateral dimension. In such cases maloc clusion of the tceth is usual; this is corrected by intermaxillary fixation of the mo bilized bony structures which also reestablishes adequate relationships between the dento-alveolar processes of the upper and lower jaws. This brings us to the subject of surgical orthodontics, a field that is just beginning to expand; its development should bring about closer collaboration between surgeon and orthodontist, resulting in rapid and efficient improvement of malocclusion. The absence of vibration characteristic of the air-driven turbine, in contrast to the mechanically driven drill, allows the surgeon to carry out delicate and precise surgical procedures with less fatigue to himself."

Microsurgery has brought about important changes and progress in the treatment of cere bral aneurysms in recent years. Only 12 years ago McKissock, one of the most experienced surgeons in the treatment of aneurysms pompared the results of operative and nonoperative treatment. He found that mortality and morbidity of cerebral aneurysms was not significantly affected by whether the patients have been operated upon or not. This view is held by many neursurgeons, and was confirmed by results of the Co-operative Study in 1969. In the review on treatment of aneurysms in Progress in Neurological Surgery in 1969, techniques such as encasement with plastic compounds, piloinjection, stereotactic copper or electric thrombosis and metallic thrombosis and profound hypothermia in anaesthesia were listed. In general, these techniques now seem to be of little more than historical interest. Progress in recent yeats has been so enormous that one may perhaps gain the impreSSion that the main problems in the treatment of aneurysms have been solved and that there are no more to be surmounted. This is dangerous and complacent thinking, such as Lord Moynihan indulged in during the thirties. For this reason we thought that the time had come to assemble a group of experts who could discuss the various unsolved and contro versial problems of aneurysm surgery in the friendly and relaxed atmosphere of a "work shop.""

In a period of controversial attitudes to thyroid cancer, this book aims to correlate recent progress in basic sciences with new clinical management possibilities. It deals with the epidemiology, pathology, pathophysiology, etiology, diagnosis, therapy and follow-up of this disease based on 27 years' experience with some 2000 thyroid cancer cases. The inclusion of ultrasound, CT, NMR imaging and modern surgical techniques for combined treatment modalities is new. Guidelines for further research and improved therapy are set and an extensive review of the literature is provided. This up-to-date survey will offer clinicians, surgeons and researchers a better understanding of thyroid cancer in its entirety.

There has long been disagreement about various aspects of the structure and function of the "gatekeeper" (Greek pyloros, from pyle = gate and ouros = guard). In recent years the problem has often been mentioned in anatomy, physiology, gastroenterology, radiology and even in nuclear medicine. For instance, while referring to manometric and gastric emptying studies, Schu- urkes and van Nuenten (1984 ) pointed out that there was considerable contro- versy as to whether a true pyloric sphincter existed in most species, and espe- cially in man. According to Reeve (1981) many functional aspects of sphincters are poorly understood; the exact mechanism of control of the transfer of chyme from stomach to duodenum through the pylorus is still not clear. Malagelada (1983) states that controversy surrounds the motor activity and function of the antro- duodenal junction; there is disagreement as to whether the pylorus functions as or as an integral part of the distal antrum. Ehrlein et al. (1984) a separate unit reiterate that pyloric motility is poorly understood, and according to Funch- Jensen (1987) there are many unsolved questions. Malagelada (1990) states that the stomach performs multiple functions with a deceivingly simple anat- omy; this is regarded as the key to the investigator's frustration when trying to uncover its secrets. One source of the many controversies surrounding the pylorus may be species differences, according to Schulze-Delrieu et al. (1984).

Advances in breast cancer research, achieved through the progress of knowledge and development of new therapies, have been translated into improved quality of care for breast cancer patients. Clinical investigations and clinical trials have made the largest contribution to the body of knowledge that finds its way to the patient. Never before during the past decades of management of breast cancer has there been such a fruitful intellectual cross-fertilization of ideas among individuals involved in the generation of hypotheses, basic research, development of drugs and treatments, conduct of clinical trials, and statistical evaluation - the results of all of which are now translated into progress in clinical care. Even issues such as the quality of life of breast cancer patients, once the domain for few, are now being openly addressed by trials and discussed in a much broader forum. The IVth International Conference on the Adjuvant Therapy of Primary Breast Cancer, also known as the st. Gallen Conference, was again attended by more than 800 scientists and clinicians interested in this broad spectrum of breast cancer research and the interactions between such diverse fields of interest and specialties as cancer pathology, molecular biology, and psychosocial oncology. This volume collects findings and conclusions presented at the conference.