The transformation of a normal cell into a cancer cell is not a sudden but a slow continuous process which may take years. A systematic study of the morphological and structural changes that take place during this cellular transformation has only become possible since methods were developed to induce a high incidence of tumors in experimental animals. The growth of such tumors can be followed during all stages of their development. For several reasons, rat liver has proved to be particularly suitable. For more than thirty years it has been known that one can induce tumors in rat liver experimentally with many different substances. The azo dyes which were used originally (YOSHIDA, 1932; KINOSITA, 1937) have since been replaced by more potent carcinogens. The recently discovered nitrosamines, dimethylnitrosamine (MAGEE and BARNES, 1956), diethylnitrosamine (SCHMAHL et aI. , 1960) and N-nitrosomorpholine (DRUCKREY et aI. , 1961) should be mentioned in this context. Used in the proper dose, these carcinogens lead within a few months to the formation of multicentric hepatomas in practically 100 Ufo of the experimental animals, and are therefore a very useful tool for studies of the cytogenesis of cancer (see BUCHNER, 1961; GRUND MANN, 1961; GRUNDMANN and SIEBURG, 1962; OEHLERT and HARTJE, 1963; BAN NASCH and MULLER, 1964). The liver parenchyma as such offers a very big technical advantage because it consists of a rather homogenous cell population.

Quick Reference Dictionary for GI and Hepatology is a unique, pocket-sized reference designed specifically to provide a magnitude of terms and their definitions, guidelines, and references essential to the gastroenterology profession. Led by Dr. Jonathan Fenkel and his contributors, this compact, concise, and informative reference contains over 1000 commonly used GI and hepatology terms and definitions. Additionally, Quick Reference Dictionary for GI and Hepatology offers more than 20 quick reference appendices related to common GI and liver diseases. Some appendices include: * Causes of acute liver failure * Approach to elevated liver enzyme tests * Peptic ulcer disease: therapy and re-bleeding rates * Colorectal cancer surveillance guidelines * Scoring of acute pancreatitis * Types of gallstones Quick Reference Dictionary for GI and Hepatology provides an at- your-fingertips guide for anyone who works in the gastroenterology profession, including gastroenterologists, medical students, residents, fellows, nurse practitioners, physician assistants, office staff, and industry sales representatives.

In their second year in medical school, students begin to learn about the differences between "disease" and "illness." In their studies of pathology they learn to understand disease as pertubations of molecular biological events. And we clinicians can show disease to them by our scans, lay it out even on our genetic scrolls, and sometimes even point out the errant nucleotide. Disease satisfies them and us; at Yale, lectures on the gastrointestinal tract run from achalasia to proctitis. There is, alas, little mention of functional bowel disease or of the irritable or spastic colon, for that is not easy to show on hard copy. Functional bowel disease represents "illness," the response of the person to distress, to food, to the environment, and to the existential problems of living. In real life such matters are most important. Richard Cabot first found out at the Massachusetts General Hospital almost a century ago that 50% of the patients attending the outpatient clinic had "functional" complaints. The figure had grown to over 80% when the very same question was reexamined 60 years later.

Drugs are often associated with adverse effects, and the digestive tract is the most frequent target. This volume collects a number of updated overviews from experts in this area to offer to the reader a single, complete source of information and reference on that subject.

In an attempt to attain the best possible delimitation of all the problems posed today by benign diseases of the esophagus, 181 authors each agreed to answer one or more of 210 questions that had been drawn up on the subject. These questions, each one deliberately limited and difficult, mostly concerned reflux esophagitis: its natural history, the means of its diagnosis, all existing treatments, and its eventual degeneration. The authors approached are today's most reputed specialists in the fields of epidemiology, gastroenterology, endoscopy, pathology, and surgery of esophageal diseases. The authors were all assigned one or more questions in their own field, none of which was simple: all did their best to synthesize in their replies their own experience on the precise point under review and included all the most useful bibliographical references on the topic. The book is thus the result of an original, individual approach to try to pinpoint the heart of a problem. The 210 answers succeed one another in logical progression according to the different diagnostic and therapeutic stages, specifying, at each step, the degree of precision sought. Consequently, the reader has at his disposal an exceptional synthesis of facts and concepts. Opening the book at random he will find at once the detail he is looking for, the professional opinion he is lacking, or the development of a question he had perhaps not yet asked himself.

The pathogenesis of cell death and necrosis in the liver is a central topic of research in liver disease. A molecular understanding of events and sequences leading to cellular death provides the basis for preventive and therapeutic efforts. This volume originates from a "Workshop on Experimental Liver Injury" held on November 9 and 10, 1974, in Freiburg, Germany. Recent progress in the elucidation of the mode of action includes agents inducing liver cell necrosis by a primary dis- turbance of nucleotide and nucleic acid metabolism as well as hepa- totoxins characterized by a primary attack on cellular membranes. I hope that this book will contribute to an increasing understanding of disease mechanisms. Freiburg im Breisgau Dietrich Keppler June 1975 Acknowledgments The generous support from Dr. H. Falk, Freiburg, has been a prereqUIsite for the organisation and publication of the meeting on "Pathogenesis and Mechanisms of Liver Cell Necrosis". I wish to express my sincere thanks for this sponsorship. I am indebted to those who acted as chairmen during the meeting: Professors H. Remmer (Tilbingen), M. Frimmer (Giessen), W. Gerok (Freiburg), H. Popper (New York), H. Schimassek (Heidelberg), and K. Decker (Freiburg).

We have been privileged to start our academic careers at the begin ning of the decade in which the immunological roles and hypersensitivity diseases of the gastrointestinal tract and liver have been defined. In the early 1960s IgA was reported to be the main secretory immunoglobulin, immunoblasts were shown to home to the intestinal mucosa and certain serum autoantibodies were described in patients with chronic liver disease. Shortly thereafter IgE and Australia antigen were discovered. Parallel advances in clinical investigation, in particular closed biopsy techniques, facilitated correlation of morphological changes with im munological mechanisms in disease of the gastrointestinal tract and liver. Only 10 years later, the concepts of immunity and hypersensitivity are regularly applied to the pathogenesis, diagnosis, treatment and prog nosis of many chronic diseases in these organs. In designing this book we have attempted to integrate theorectical and clinical immunology as they pertain in 1975; our ultimate aim is aptly described by Brachet as quoted by Professor Paronetto (page 319). We would like to think that this review provides a basis for the next major advances in the fields of gastrointestinal and hepatic immunology. As we see it, the outstanding problem in both sites is how to produce protective immunity without hypersensitivity."

Ever since the emergence of the concept of catharral jaundice by Virchow, viral hepatitis has eluded scientists as a pathogenetic enigma. A tremendous new impetus was given to hepatitis research by Baruch Blumberg's discovery of his 'Australia Antigen', now known as hepatitis B surface antigen. This led to an unheard-of outburst of research activity to elucidate the nature of the virus, its chemical and antigenic composition, its epidemiology, and pathogenetic mechanisms in the causation of liver disease. Coinciding with this period, modern medical science witnessed impressive progress in the analysis of the extraordinarily complex mechanism of immunological reactions. Immunohistochemical techniques for the detection of hepatitis B viral components are a product of this scientific progress in both areas. The application of such tech niques forms the core of this work. It represents a vast amount of work, performed during the course of several years, with meticulous application of advanced immunohisto chemical techniques, combined with histopathology and clinical-patho logical methods. This has resulted in the compilation of original results and new insights into the cellular and tissular localization of the anti genic components of the hepatitis B virus in different forms of chronic liver disease. The most outstanding results are the demonstration of the superior sensitivity of the applied immunohistochemical technique in the search for viral components in chronic hepatitis patients. and the differ ential distribution patterns of hepatitis B surface antigen in the various forms of chronic liver disease."

Material for this book was gathered in the early 1980's in Manchester, where a higher incidence than usual of complications in the gastro-intestinal and urinary tract was observed. Part I describes the principles and methods of radiotherapy for pelvic tumours, pathological features and radiological analysis of bowel and urinary tract changes. Parts II and III are devoted to clinical assessment and management, where the need for a multi-diciplinary approach is emphasized.

More than a century ago, Cripps successfully employed the direct and complete division of the anal sphincters as a means of approaching the lower rectum and anal canal, and reported on a series of 36 patients who had been treated in that fashion. Cripps was pleasantly surprised to find good fecal continence in over two-thirds of the patients during later follow-ups, despite the fact that the divided sphincters had not been repaired. The transsphincteric procedure was largely forgotten in subsequent years, however, and only the parasacral proctotomy of Kraske, which spared the anal sphincters, can be said to have gained an established place in the" surgical armamentarium. " It remained for York Mason to redirect the attention of the surgical community to the great potential of the trans sphincteric approach and the excellent continence that can be achieved through adequate repair of the divided sphincters. Having recognized the outstanding practical value of this procedure, we felt it necessary to define more precisely the anatomical prerequisites that would ensure minimum operative bleeding, and to bring the procedure more in line with current knowledge of normal continence and defecation. Dr. A. Huber, in consultation with the director of the Institute for Clinical Anatomy of our surgical department, Prof. A. von Hochstetter, did many months of dissection work on fresh anatomic preparations in an effort to explore and refine the various aspects of the trans sphincteric ap proach."

In the rapidly evolving field of Helicobacter infection new data on pathogenetic and pathophysiological mechanism have appeared. New methods which will be more sensitive and specific in the diagnosis of the infection are being developed and in this proceedings the first attempt using PCR technology is published. From the clinical point of view, a challenging aspect that needs clarification, is the observation which suggests an appearance of a correlation between the presence of the bacteria and abdominal pain and other symptoms in children whereas in old age no such correlation is evident. The relationship of H. pylori and gastric cancer is studied with histopathological data and epidemiological approaches. On the treatment side schemes using short courses and new antibiotic combinations are being investigated and preliminary data are reported.

The larvae of Anisakis, whose adult form lives on sea mammals such as whales, seals, and dolphins, are parasitic upon many species of salt-water fish. When the final host animals eat paratenic hosts, the larvae grow to adulthood in the hosts' stomach. However, when hu mans eat these infested fish, the larvae die instead, causing a disease called anisakiasis. In 1960, in the Netherlands, van Thiel et al. found a worm in the intestinal wall of a patient who had eaten raw herring and had suffered symptoms of acute abdomen. The impact of this report was tremendous among Japanese parasitologists because of the Japanese habit of eating raw fish. In 1964, the Special Research Group from the Ministry of Education was established to investigate the disease, stimulating progress in the study of anisakiasis. Three types of worm, Anisakis simplex larva (previously known as Anisakis larva type I), Anisakis physeteris larva (Anisakis larva type II), and Pseudoterranova decipiens larva type A, are believed to cause anisakiasis. As many as 165 kinds of fish and squid in the seas near Japan are hosts to Anisakis simplex, and 9 species are hosts to Pseudoterranova decipiens larvae. Contra caecum has experimentally been observed to invade the gastrointestinal tract, but no infection by this larva has been reported in humans. A case of infection by Pseudoterranova decipiens type B has been described. In Japan, the name Terranova decipiens (Shiraki 1974) has been adopted instead of Phocanema decipiens (Mozgovoi 1953)."

The literature of medicine continues to expand at a remarkable pace. The number of papers and monographs published has increased dramatically in the past five years. Nowhere has this increase been as dramatic as in the field of acute and chronic hepatitis. Why then should there be still another book? Despite the sheer volume of words published, it is still difficult to find in anyone volume a compilation of all of the most significant work. Most mono graphs have considered either chronic or acute hepatitis, not both. Few works have addressed both the clinician and the basic scientist. This book addresses both of these audiences and considers both of these diseases. It was designed to provide an authoritative but concise assessment of our changing concepts of acute and chronic hepatitis. It covers what is currently known and, based on the most convincing research, believed about these diseases. To fulfill this ambitious goal, only authors with international reputations in their fields of expertise were invited to contribute. In the evolution of our current thoughts on the pathogenesis and manage ment of acute and chronic hepatitis, our ideas have changed several times. This book presents the facts as they are known today and, in areas where all the facts are not established, presents the well-founded opinions of those considered to be authorities. The authors present established and usually confirmed data and do not deal extensively with areas of speculation or unconfirmed material."

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.

This study assembles current and new information on the mechanisms involved in intracellular calcium regulation and their actual or potential relationship to cellular calcium transport. Topics discussed in detail are calcium channels, cellular calcium extrusion, sodium/calcium exchange, calcium-binding proteins with special reference to the vitamin D-induced calbindin, calcium transport and disorders thereof. Each topic is introduced with an overview followed by research papers dealing with relevant topics in each category. New information deals with calcium channels which are not voltage-sensitive, the structure and function of the plasma membrane Ca ATPase, the role of the Na/Ca exchanger in intracellular Na and proton regulation, a comprehensive overview of calcium transport with quantitative analysis of the role of the intestinal and renal calcium-binding proteins, description of the structure and function of the calbindin genes, and identification of calcium transport defects in diabetes and hypertension. Readers will be brought up-to-date on current knowledge and concepts in this rapidly expanding field and be directed to the relevant primary and secondary literature.

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.

Since the beginnings of diagnostic ultrasound in the 1950s, each decade has seen significant advances in this technology. Commer cialization of ultrasound occurred during the 1960s with the introduction of many of the clinical uses that are in existence today. The 1970s showed the most dramatic changes with the commercial introduction of gray-scale and real-time ultrasound. In the 1980s many new advances were introduced, including color Doppler, as well as a wide variety of endoluminal approaches, including endorectal, endovaginal and transesophageal. The decade of the 1990s promises even more significant advances with further transducer miniaturization, three-dimensional ultra sound, and the introduction of a variety of ultrasound contrast agents. With such rapid changes occurring, it becomes important to disseminate knowledge in as rapid a fashion as possible, thus it was quite appropriate that a meeting such as this be held to provide an in-depth review of the many new areas of ultrasound imaging that show promise for the future. Emphasis was on the new uses of ultrasound in gastrointestinal diseases. Many of these advances will, of course, also have applications in many other areas of the body. It is hoped that those in attendance will acquire a much broader understanding of where ultrasound is now and where it is headed in the not too distant future.

Helieobaeter pylori has recently been recognized as a new genus according to specific taxonomic criteria; the "popular" name Campylobaeter pylori has been corrected by scientific progress. Following the discovery of the spiral microorgan ism in gastric mucosa by Marshall and Warren in 1982, it took only a few years for H. pylori to become established as a factor in the pathogenesis of gastritis and peptic ulcer disease. Interest in different aspects of H. pylori has grown continuously and has attracted scientists from various medical and biological disciplines such as gastroenterology, microbiology, pathology, immunology, and pharmacology. Indeed H. pylori provides an excellent model for interdisciplinary interaction and cooperation. To promote this concept of interdisciplinary research and exchange of knowledge, a European Campylobacter (Helicobacter) Pylori Study Group was founded in 1987 in Copenhagen. The second meeting of this expanding group was held from October 12-14,1989 in Ulm, FRG. The fact that more than 500 participants attended the conference and that 187 original contributions from all five continents were presented clearly confirmed that H. pylori has "scientifically infected" the whole world. Our understanding of the microbiological and pathogenetic aspects of H. pylori is continuously being challenged as new results follow swifthy from different research areas. This book includes an update and progress report on the various aspects of H. pylori presented and discussed in special workshops held during the meeting in Ulm.

Provides findings on acute pancreatitis in the fields of morphology, epidemiology, pathophysiology, enzymatic and in- strumental diagnosis, clinical aspects and pharmacological and surgical treatment. Emphasis on clinical implications on the local release and vasoactice and toxic substances, the high rate of bacterial infection in the necroses, and the causes of impairment of cardiocirculatory, pulmonary and re- nal organs.

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).

Imaging of Gastrointestinal Tract Tumors describes current imaging practice for the most commonly encountered benign and malignant digestive tract tumors and gives a review of the literature for less frequent tumors. General features (anatomic data, frequency, clinical and biologic signs, treatment) are discussed for all pathologies prior to description of imaging techniques, which include barium studies, ultrasonography and angiography, and above all CT. MRI appears particularly indicated for esophageal carcinoma and pelvic recurrences of colorectal cancers. The book is divided into three main section - benign tumors, malignant tumors, and tumors with an indeterminate prognosis - reflecting the value of different imaging strategies as a function of a tumor's natural history. The thorough analysis of literature for both frequent and less common tumors allows global evaluation of the diagnostic possibilities of imaging techniques, making Imaging of Gastrointestinal Tract Tumors a reference work for all specialists concerned with digestive tract pathologies.

Only a few years ago, most treatises on sonography covered all the diagnostic applications of ultrasound, de scribing organs from the brain down to the placenta. Dr. Bruneton and his associates must be thanked for pre senting this book devoted to the spleen. It probably offers the most complete presentation of details and the richest images available in its field. This book will thus become the ultimate reference in most libraries of books on son ography. March 1988 F. Weill The authors wish to thank Christine Rostagni, Fran ise Fein, and Bernard Fontaine for their assistance in the preparation of this book. Contents 1 Sonographic Anatomy of the Normal Spleen, Normal Anatomic Variants, and Pitfalls B. Senecail . . . . . . . . . . . . . . . . . . . . . . 1 1. 1 Anatomy of the Spleen. . . . . . . . . . . . . . . . 1 1. 1. 1 Morphology and Structure . . . . . . . . . . . . . 1 1. 1. 2 Location and Relations of the Spleen. . . . . . . . 3 1. 1. 3 Average Dimensions of the Cadaver Spleen . . . . 5 1. 1. 4 Congenital Anomalies and Normal Variants. . . . 5 1. 1. 4. 1 Fissured Spleen. . . . . . . . . . . . . . . . . . . . 5 1. 1. 4. 2 Lobulated Spleen. . . . . . . . . . . . . . . . . . . 5 1. 1. 4. 3 Spleen with Two Hili. . . . . . . . . . . . . . . . . 5 1. 1. 4. 4 Wandering or Ectopic Spleen . . . . . . . . . . . . 6 1. 1. 4. 5 Numeric Anomalies . . . . . . . . . . . . . . . . . 6 Ultrasonography of the Spleen . . . . . . . . . . . 1. 2 6 1. 2. 1 Equipment . . . . . . . . . . . . . . . . . . . . . . 6 1. 2. 2 Patient Examination . . . . . . . . . . . . . . . . . 7 1. 2. 3 Scanning Technique . . . . . . . . . . . . . . . . . 7 1. 3 Sonographic Features of the Normal Spleen. . . . 7 1. 3. 1 Splenic Contour . . . . . . . . . . . . . . . . . . . 7 1. 3. 2 Echo Pattern of the Splenic Parenchyma. . . . . ."

The aim of this symposium was to provide a framework for fruitful discussion on intestinal transport, not only for advanced scientists but also for younger people starting in this field of research. Invited lectures, communications and poster presentations were focused on four central themes, all treating the prop erties of the sole intestinal epithelium, deliberately leaving aside problems dealing with more integrative functions of the whole intestine. The importance of motility or blood circulation, for instance, is certainly capital in the overall intestinal function, but these aspects by themselves deserve another meeting. This volume has compiled the manuscripts of the invited lectures which sub stantially comprised the four sessions of the Symposium. Part 1 is designed to emphasize actual knowledge of the transport of water, inorganic as well as organic ions and molecules across the isolated intestinal epithelium. An enormous wave of investigations has emerged from studies per formed with "Ussing chambers," which roused interest in studies on absorption mechanisms and subsequently on secretory processes. This has triggered off a trend to research on isolated cells as absorption and secretion are the main func tion of the different cell types constituting the intestinal epithelium. In this first session not only the importance of the parallel arrangement of these different cellular entities is stressed, but also the role played by the paracellular route."

Dr. Raymond Pederson, Dr. Jill Dryburgh and I commenced work on GIP in 1968, when, with the generous help of Professor Viktor Mutt and Professor Erik Jorpes of the Karolinska Inst, itute, Stockholm, we were able to establish that there existed an inhibitory material for acid secretion in cholecystokinin-pancreozymin prepara tions. Once the physiological evidence for the inhibitor was established it seemed appropriate to seek help in its isolation. Dr. J. Dryburgh and Dr. R. Pederson were left to bioassay fractions in Vancouver whilst I enjoyed the company of Professor Mutt at the Karolinska for one year, as a Medical Research Council of Canada Visiting Scientist. Purification of the inhibitory factor proceeded rapidly due, in no small measure, to Professor Mutt's untirmg efforts on my behalf. Later that year, Dr. Dryburgh joined us in Stockholm to begin the sequence work on GIP. This was completed late in 1970 in Vancouver. In Stockholm in June 1970, I met a fellow Canadian Dr. John Dupre (McGill University) at a cocktail party who kept commenting about the possibility of GIP being an insulinotropic hormone, the "incretin" of earlier days. At that time, gastrointestinal physiologist as I was, I did not recognize the importance of his comment. This became apparent two or three years later when Dr. Dupre demonstrated that GIP was insulinotropic in man. In 1972, Maryanne Kuzio and Dr."