Hepatology has come of age in the last decades. Biology of the liver has flour ished long before. As the largest homogeneous organ of the body the liver served as useful model in the development of biochemistry and related discip lines. Only gradually were these biological investigations applied to the clinical study of liver disease. This was particularly stimulated by the recognition that in the greater part of the world, the developing countries and what we now call the Third World, liver disease represents a major threat to overall public health. It leads to morbidity and mortality of persons in their productive years from liver cancer, cirrhosis and parasitic disease, particularly, schistosomiasis. Moreover, the growing emphasis on the social impact of diseases focused on disorders of the liver because malnutrition, poverty, and drug addiction contrib ute greatly to their spread. This is compounded by the increase of alcohol abuse, recently on the rise even in the developing countries. Concern with envi ronmental pollution has also raised the interest in liver diseases, in part because the liver acts as a guardian against polluting chemicals and in part because it is considered, possibly to an exaggerated degree, a vulnerable target of such chemicals.

Hepatic cells are involved in the metabolization and elimination of a variety of endogenous and exogenous substances. They mediate the uptake, processing and subsequent secretion of biliary compounds, such as various drugs or hormones, and the passage of metabolites to be released into different blood compartments. To perform vectorial passages hepatocytes show a strong polarity with sites for endocytotic processes or specific carrier molecules, and a specified system of organelles for intracellular transport and sorting, metabolization and secretion of compounds. Several aspects, e.g. regulation, control and mechanisms of hepatic traffic are reported in detail - complemented by methodological approaches to analyse and monitor these processes.

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.

Campy/o/meler pylori was described for the first time in 1983. Up to now more than 100 papers have been published dealing with its microbiological properties and its clinical implications. The lime has come to survey the field, to evaluate the hith erto accumulated information, and 10 discuss the questions thai should be answered in the ruture. It was for these purposes that the First International Symposium on Campy/abaeter pylori was held. bringing together specialists from a variety of discipl ines, including basic scientists as well as clinicians. This book is based on papers given at the symposium. We are very grateful 10 Rohm-Pharma for undertaking to sponsor this meeting, and to Mrs. C. 1. Klein and her starr for the impeccable organisation which permillcd us to work in such a pleasant environment, In the interest of rapidity of publication, we have reduced the amount of editing to a minimum and have not, in any sense, "re fereed" the discussions, which were written by the contributors at the time of the question-and-answer session. They were also veiled by their authors at the proof stage, and we have done our best to retain their original spontaneous flavour. We hope, in this way. 10 have produced a satisfactory record of the events and an up-Io-dale overview of research on Campylobacrer pylori."

It gives me great pleasure to have this opportunity to write a Foreword for this new book. In the past two decades we have witnessed very significant advances in the management of the very ill patient. The great success in this field of medical endeavour is largely due to the establishment of intensive care units, but a great deal of progress can also be attributed to the major developments in technology, which affect patient management and care as well as the many sophisticated techniques of diagnosis and patient monitoring. Imaging and Labelling Techniques in the Critically III covers this new important and difficult field of diagnosis and visual monitoring. By establishing the criteria and algorhythms for the choice of the different methods available for this purpose, defining the diagnostic signs on images and resolving some of the mis conceptions and pitfalls, this book will go a long way to help the reader, particularly those involved in the care of patients in the intensive care units. This book brings together many different methods of investigation and discusses the advantages and limitations of these techniques in different clinical circumstances. Some of the techniques are well established and their usefulness in the intensive care unit is in no doubt. Some of the newer techniques such as PET scanning or NMR imaging have not yet found a defined position of usage in the critically ill patient. There is, however, little doubt that in due course this situation will change.

Based on the results of the latest congress of the European Association for the Study of the Liver (EASL), this volume makes excellent reading since it explores in detail the role of free radical reactions in liver diseases. Studies in recent years using various methods have shown that free radicals play an important role in toxic liver disorders. For this reason, the current scientific knowledge is presented in this balanced, clinical portrayal. The account refers to the many observations, experiencesand evaluations that have been made both clinically and experimentally. Two major areas discussed concern the pathophysiological changes by free radicals and the therapeutic possibilities that have come to light.

A new presentation of physiological regulatory mechanisms and therapeutic applications is given in this book. It represents a collection of the most up-to-date information in cholecystokinin (CCK) research, especially focusing on the development and characterization of CCK antagonists. The book contains chapters on the synthesis, biochemical and pharmacological characterization of potent and selective CCK antagonists as well as physiological applications of these compounds. The last section of the book is devoted to the involvement of CCK in pathological states and potential clinical applications of CCK antagonists.

by Dr. Jan. J. Smulewicz Ultrasound imaging has reached a stage of sophistication where by diagnostic information can be gained without discomfort to the patient and with complete absence of morbidity and mortality. The procedure is quick, safe, noninvasive and in many instances can supersede and obviate more time-consuming procedures requiring catheterization, injection of a contrast material, and radiographic imaging. In obstetrical problems the danger of ionizing radiation to the fetus is eliminated. In debilitated and very ill patients this simple and painless method becomes the procedure of choice. Unique features of ultrasound equipment allow for pinpoint local ization oflesions and direct visual guidance of percutaneous puncture techniques for aspiration and biopsy. The accuracy of ultrasound guided punctures and the absence of side effects make this modality far superior to percutaneous invasive techniques performed with other imaging systems. Renal cyst puncture and amniocentesis are but two of the procedures in which ultrasonic guidance is the method of choice. v Dr. Hassani has throughly explained and carefully explored the wide variety of exam inations available with ultrasound. The large volume of material and the clear interpre- tion makes this book of great interest to all of the medical profession. In addition to the existing methods available for diagnostic in terpretations, this method of noninvasive diagnosis should find its way into every hospital or center where good medical care is provided. JanJ. Smulewicz, M.D."

Basic and clinical research have in recent years contributed towards clarifying certain aspects ofthe epidemiology, pathogenesis, prevention, and treatment of liver diseases. New diagnostic techniques have, moreover, facilitated observations on the evolution of such diseases. Nevertheless, a numberofquestions still remain, especially in the assess- ment and management ofliver patients. The hope that such questions can be answered justifies publications like the present one, which provide experts an opportunity to pre- sent the results oftheir research. The papers collected in this volume cover all aspects of the assessment and man- agement of hepatobiliary disease. The focal points are three summaries ofthe state of the art. The first deals with the highly topical problem of liver transplants from the point ofview ofpatient selection. Roger Williams in fact stresses the urgent need to ex- ercise caution in the selection ofsuitable candidates. This is especially true at the pre- sent time when cyclosporin A, a new immunosuppressive drug now available on the market, has significantly changed the natural history ofsurvival after liver transplanta- tion.

Major advances have been made in the understanding of the molecular mechanisms of atherosclerosis, the disease that still affects more than 50 percent of the population in the highly industrialized countries. This volume covers the most recent advances in the treatment of hyperlipidemia. It represents a necessary update because molecular mechanisms of atherogenesis have been discovered in the past few years and their molecular mechanisms of action identified. Extensively treated are the molecular mechanisms of disease etiology of arteriosclerosis in relation to the major risk factor "hyperlipidemia," rationale for more effective treatment of this disease by dietary means, the treatment of associated or causing diseases, and the treatment using hypolipidemic drugs.

The last decade has seen tremendous developments in many fields of gastroenterology and hepatology. The aim of this series is to highlight some of these topics that deserve particular interest. Research in the field of viral hepatitis has been very intense and successful in recent years. The hepatitis B virus is one of the best explored at the current level of virology. Not only the nucleotid sequence of the viral DNA can be decoded, but also the amino acid compounds of its genetic products are known today. Since the techniques of molecular biology have increasingly found access to clinical laboratory use, hepatitis B virus infection can serve as an example for the importance of molecular biology in clinical hepa tology. Another example for the interdependence of basic science and clini cal medicine represents the research on bile acid metabolism. The investigation of bile acids has revealed new diagnostic approaches to hepatic and intestinal disorders. Commercial kits for the routine measurement of serum bile acids in clinical laboratories by enzymatic or radioimmunologic techniques are now available. The diagnostic value of these measurements in gastroenterology and hepatology shall be defined. Another aspect of bile acid research leads to new per spectives in the treatment of gallstone disease. The dissolution of cholesterol gallstones by chenodeoxycholic acid (therapy) may be quoted as the best example for the development of new phar macotherapeutic principles derived from basic bile acid research."

There have been many advances in the field of gastrointestinal pa thology which are of considerable clinical significance during the 13 years since the last publication of a volume of Current Topics in Pathology devoted to this subject. Many have arisen from the app lication of new techniques of histochemistry, immunocytochemi stry, quantitative morphometry and molecular and cell biology to gastrointestinal diseases, but some, notably the recognition of the association of Campylobaeter pylori with the commonest type of chronic gastritis, have been achieved using such long established 'routine' histological procedures that one wonders how their signifi cance had escaped recognition for so long. The topics covered in this volume have been selected because they present advances of relevance to the diagnostic clinical pathologist. However, they re present the personal selection of the editor, and are in no way exhaustive. Many other examples of progress in our understanding of the pathophysiology of gastrointestinal diseases have been omit ted, either because of the confines of space or because they have been well reviewed recently in other publications. Most of the workload of the practising gastrointestinal patholo gist involves the diagnosis and assessment either of inflammation or of neoplasia in the alimentary tract, and this is reflected in the topics presented in this book."

Hepatocellular carcinoma (HCC) is common in the Far East and South Africa, but is rare in the United States and Europe. The vast experience of the East, which has led to marked improvement in the prognosis of patients with HCC, is made available to researchers worldwide in this monograph. The book is based on an enormous amount of data that has been collected and analyzed by the Liver Cancer Study Group of Japan. The data stems from a survey on HCC in Japan since 1965 and contains information from more than 30,000 patients with regard to age distribution, past medical history, diagnostic procedures, frequency of HBV-associated antigens and antibodies, surgical and conservative treatments, gross anatomical and histological features of the tumors, pathology of the noncancerous portions, distant metastasis, and survival rate. This data is a tremendous contribution to our understanding of the epidemiology, pathology, and the latest developments of the molecular biology and clinical problems of primary liver cancer.

Adenomatous Polyps of the Colon: Pathobiological and Clinical Features consolidates the vast body of basic science and clinical data associated with adenomatous polyps of the colon, much of it inspired by the realization that most colorectal carcinomas seem to arise in such polyps. This book strives to evaluate these data, with particular emphasis on their implications for management of polyp-bearing subjects. Topics comprehensively explored include anatomy and histology of the normal colon; pathologic characteristics of adenomatous polyps, differential diagnosis, and grading schemes for degree of dysplasia and villosity; adenomatous polyposes; histologic and epidemiologic evidence for the malignant potential of adenomatous polyps; and detection and management, with special attention to endoscopy, endoscopic polypectomy, the malignant polyp, and post-polypectomy surveillance schedules.

The last few years have witnessed major developments in molecular biology which have had a significant impact on biomedical knowledge. As a result new concepts in cell biology have emerged, new etiologic agents have been discovered, and new drugs have become available. Furthermore, the world of mediators, cytokines, and humoral factors has enlarged considerably in a relatively short period and this has modified our views of diverse physio pathologic processes as well as opened up new therapeutic prospects. In addition, recent technologic advances have revolutionized our diagnostic methodology and have greatly enhanced the power of our therapeutic resources. All these factors have contributed to a substantial remodeling of both liver science and clinical hepatology, and these changes have generated the motivation for the production of the present book, which attempts to give an account of well-known clinical facts in the light of current thinking. It is the fruit of the coordinated work of experts from different countries in three continents. In a sense, it is a manifestation of the fact that inter national cooperation is becoming increasingly important not only in the expansion of science but also in its exposition. We hope that Hepatobiliary Diseases will be useful to both students and clinicians and that internists, gastroenterologists, and general practitioners will find in its contents a satifactory coverage of their field of interest."

This book has its roots in a monograph on cancer of the esophagus and gastric cardia edited by us in 1965 and published in Chinese on ly. Along with a number of colleagues in various fields, we summa rized our work in the epidemiology, pathology, diagnosis, radiother apy, and surgery of carcinoma of the esophagus and gastric cardia, carried out chiefly at Peking Union Medical College Hospital, Fu wai Hospital, and the Cancer Institute of the Chinese Academy of Medical Sciences during the 25 years from 1939 to 1964. In the 18 years since the publication of that monograph, further progress has been made in China in various aspects of research and surgical treatment. Abundant material has been accumulated on the long term results of surgery, and a number of newer principles and meth ods for diagnosis and management have been evolved. In order to meet the need for the exchange of scientific and technical informa tion, both domestically and internationally, we have invited a group of our current colleagues working on the different aspects of carci noma of the esophagus and gastric cardia to contribute to the pre sent volume, which is being printed in both Chinese and English. The Chinese edition, like the original monograph, is being publish ed by Shanghai Science and Technology Publishers. Through the kind invitation of Dr. Heinz Gotze, the English text is being publish ed for international circulation by Springer-Verlag.

The LEC strain of rats, which spontaneously develop acute hepatitis as sociated with jaundice, chronic hepatitis, and ultimately hepatocellular carcinomas, was established by scientists in Sapporo, Japan. Careful ob servation and breeding led to the initial discovery of this characteristic, inherited liver disease in rats. Subsequent collaboration between scientists in Sapporo and other centers has revealed an autosomal recessive nature of inheritance, along with a variety of histopathological and biochemical findings. The causative mechanism(s) underlying this abnormality remained a mystery for some time, providing a challenge for many scientists who were attracted to the quest for clues to this enigma. In particular, the mech anism of spontaneous development of hepatocellular carcinomas in rats overcoming the acute phase of hepatitis and surviving with chronic hepatitis proved extremely interesting, because the involvement of a causative virus had been excluded in the early stages of investigation. Professor Michio Mori of Sapporo Medical College played a key role in the study of LEC rats, especially in the elucidation of the pathogenesis of hepatitis and hepatocellular carcinoma. He is one of the editors of this monograph which is composed of original contributions by the many scientists who have carried out their own studies on LEC rats. Of the various histopathological and biochemical alterations which have been reported, some are clearly secondary or tertiary events sequential to the primary change caused by gene mutation."

It is a great pleasure for me to introduce and to recommend this much needed text on double contrast examination of the colon. It is aimed both at clinicians who request X-ray examinations of the colon and at radiologists who must per form and interpret these studies. Over the past decade there has been renewed interest in X-ray examination of the colon despite the tremendous advances in endoscopy and imaging tech nology. This renewed interest is evidenced by the proliferation of new books on radiology of the colon. However, previous discussions of double contrast ex amination have concentrated primarily on the technique with too little attention to the understanding and interpretation of the radiologic images. This volume is unique in its emphasis on the basics of image formation and interpretation. It emphasizes the importance of the anteroposterior relation ships of the colon in determining the distribution of barium and air. It also rec ognizes the influence oflocation on the radiologic appearance of the lesion. The authors demonstrate a profound understanding of the principles of double contrast diagnosis as applied to the colon. They also have a good grasp of the gross pathologic changes underlying the radiologic images. The material is presented in a logical and analytical method which should be particularly useful to the beginner in this field. There are many helpful diagrams and the ra diographic illustrations are of excellent quality."

The following papers were presented at an international symposium on the mechanisms and treatment of nausea and vomiting in man held in Oxford in 1984. I believe that this meeting was the first occasion on which representatives from such a wide variety of scientific and clinical specialities had come together to review and debate the spectrum of the vomiting phenomenon. An attempt was made to put before an invited international audience all the pertinent facts on the different facets of the topic and then to encourage extensive discussion of the contentious issues. The first day of the meeting was devoted to the basic science ap proach to the problem and the second day to the more clinical aspects. This format has been broadly retained in the layout of the book, with the addition of summary chapters reviewing each day's contributions and focusing upon areas of particular importance. Acknowledgement must here be made to the enormous input from the many participants who either spoke in the debate or rose and themselves gave small presenta tions in addition to those of the invited speakers. The meeting occurred at a time of increasing interest in the problem of nausea and vomiting, especially because of its importance in cancer chemotherapy and radiation therapy, and even in space travel."

During the 7th International Bile Acid meeting held in Cortina d'Ampezzo., Italy, during March 1982, there were two important Workshops dealing with recent advances in two areas of bile acid metabolism - Serum Bile Acids i, n Health and Disease and The Pathophysiology of the Enterohepatic Circulation. These Workshops complemented the broad range of topics in bile acid metabolism which were presented formally as part of a Postgraduate Course. The proceedings of these formal presentations have already been pub lished by MTP Press under the title Bile Acids in Gastroenterology but in view of the exciting, important, new information which emerged during both Workshops, the organisers of the meeting felt that it would be valuable to record and edit the proceedings of the Work shops, which form the basis of this volume. The advent of new techniques for measurement of total and indi vidual bile acids in serum now means that accurate and reliable 7 PREFACE measurements of bile acids in peripheral circulation are available to all. This has resulted in a veritable explosion of information in the serum bile acid field and, therefore, the appearance of a critical evalu ation of the technical and basic scientific and clinical aspects of measuring serum bile acids is indeed timely."

Diagnostic ultrasound is changing dramatically because of the development of a variety of high resolution real-time scanning instruments. Until recently the standard instrument was the articulated arm contact scanner. Real-time scanners were viewed as adjunct instruments for specific and limited pur poses. The roles are reversing with real-time instruments more frequently accepted as the primary diagnostic tool and the contact scanner becoming the ancillary instrument for use mainly for viewing a large field that cannot be scanned with real-time instruments. Two recent editorials stated that real-time instruments were used as the sole diagnostic instrument for between 80% [Cooperberg (2)] and 98% [Bartrum and Crow (1)] of their abdominal examinations. This book introduces the reader to the field of real-time scanning in the abdomen. It presupposes an understanding of basic physical concepts of ultrasound, the appearance of both normal and pathologic conditions as produced by static articulated arm contact scanning, and a familiarity with the techniques of contact scanning. It is designed to acquaint the reader with the spectrum of real-time instrumentation, provide a basic understanding of the physics of ultrasound as related to these instruments, emphasize the special skills required in the use of this equipment, and describe applications of real-time scanning for various parts of the abdomen. While numerous illustrations of both normal and pathologic anatomy are shown, the book is an all-inclusive study of abdominal pathology as demonstrated by real-time imaging.

The development and the widespread clinical application of various di agnostic imaging modalities, such as diagnostic ultrasonography, X-ray computed tomography, single photon emission computed tomography, and magnetic resonance imaging, have been beyond all expectation. In particular, ultrasonography and X-ray computed tomography have be come major diagnostic tools for diseases of the liver, the biliary tract, and the pancreas. They often have virtually replaced other conventional imag ing modalities including invasive angiography and percutaneous trans he patic cholangiography. One modality may complement or conflict with another or other modalities. Each modality should be carefully selected with due regard for its diagnostic efficacy. In this book, the first section contains nine chapters dealing with current techniques of each diagnostic modality applicable to the liver, the biliary tract, and the pancreas. The second section deals with diseases of the liver, the biliary tract, and the pancreas and takes the form of case presentation with discussion of the significance of diagnostic imagings and diagnostic procedure. Preparation of the manuscript was made possible by the help of Dr. S. Fujita, who prepared the photographs, and Mrs. Sobajima, who typed the original manuscript. Dr. S. Miura and Miss Y. Shimizu under took the labor of translating our manuscript from Japanese into English. I would like to express my deep appreciation to all these persons, as well as to the contributors to this book, and also to the publishers, Shujunsha, Japan and Springer-Verlag.

The development and improvement of new technologies have made pancreatic disease more accessible to diagnosis in the last decade. The cooperation and coordination of experts in the fields of gastro enterology, radiology, biochemistry, immunology, and pathology are necessary if the methods are to be made available and the progress made to be fully exploited. Each of the new methods requires special training, and extensive experience is needed to guarantee high standards in the diagnosis of pancreatic disease. New methods have to be tested carefully against established diagnostic procedures, though at the same time we must be ready to adopt a new approach to diagnosis. The aim of this book is to update the material already published and to focus on the various imaging methods and functional tests currently available, the features specific for each, and their integrative potential in the detection of pancreatic disease. The various pathologic findings are analyzed with reference to the clinical stages of pancreatic disease. As an introduction to the morphological and functional features of acute pancreatitis, chronic pancreatitis, and pancreatic cancer revealed by the different imaging methods and functional tests, basic knowledge of the patho-physiological and pathomorphological events is provided by research workers. This knowledge is essential for the understanding and interpretation of the diagnostic findings recorded in pancreatic diseases.

This book represents the culmination of the major aspect of Dr. Margot Shiner's professional career. It was she who devised the technique of jejunal biopsy which opened up whole new fields of small intestinal research, including microbiology, immunology, histochemistry and histopathology, thus greatly expanding our knowledge of fundamental aspects of absorptive patho physiology. Later the application of electron microscopy demonstrated the individual cell with its mechanisms both for absorption and for the production of so many chemicals such as mucus, enzymes and hormones. Like the vision from the peak in Darian, it opened up new worlds. The contribution to our understanding of cell structure and function has been greater than the direct elucidation of specific diseases but nevertheless, there are pointers to different mechanisms which could have wide applications. It is a book which serves a double function: On the one hand it is highly technical and a publication for the super expert, recording new landmarks of knowledge and interpretation. On the other hand, it is a book which can indeed fire the imagination of the rising generation of gastroenterologists, paediatricians, pathologists and medical scientists. Having seen the emergence of the art and science of present-day gastro enterology within my professional lifetime and having been able to provide the facilities for her work in the very early days, it is with particular pleasure and pride that I write this foreword."

Exciting major changes have occurred in the understanding and treatment of gallstone disease over the last two decades. In bygone years, books about gallstones were often based on postgraduate lectures which the author, usually a surgeon of distinction, had given. More recently, many books dealing with this subject have been based upon national or international conferences. The single-author text has the disadvantage that few authors today can authoritatively encompass a whole field: the reports of symposia, conferences or workshops often lack balance and auth ority. The merits of 'Gallstone disease and its Management' edited by Malcolm Bateson are clear. He has chosen 11 authors, all of whom write on topics relating to their own expertise, and the content of the book has been carefully planned to reflect the most modern ideas about the aetiology and management of cholesterol gallstones. It is worth repeating that we are experiencing rapid developments in the field of gallstone disease. Disappointingly the least progress has been made in identifying the cause (or causes) of the disease notwithstanding the many data implicating a variety of environmental factors. Most of these affect the chemistry of hepatic bile and the contribution of the gallbladder to lithogenesis remains uncertain and unstudied."