The purpose of this series of volumes is to present a comprehensive view of the complications that result from the use of acceptable diagnostic and therapeutic procedures. Individual volumes will deal with iatrogenic complications involving (1) the alimentary system, (2) the urinary system, (3) the respiratory and cardiac systems, (4) the skeletal system and (5) the pediatric patient. The term iatrogenic, derived from two Greek words, means physician-induced. Originally, it applied only to psychiatric disorders generated in the patient by autosuggestion, based on misinterpretation of the doctor's attitude and com ments. As clinically used, it now pertains to the inadvertent side-effects and com plications created in the course of diagnosis and treatment. The classic categories of disease have included: (1) congenital and developmental, (2) traumatic, (3) infectious and inflammatory, (4) metabolic, (5) neoplastic, and (6) degenerative. To these must be added, however, iatrogenic disorders-a major, although gen erally unacknowledged, source of illness. While great advances in medical care in both diagnosis and therapy have been accomplished in the past few decades, many are at times associated with certain side-effects and risks which may result in distress equal to or greater than the basic condition. Iatrogenic complications, which may be referred to as "diseases of medical progress," have become a new dimension in the causation of human disease."

The secretion of bioactive products by tumors of the gastroenteropancreatic system results in the development of watery diarrhea that can lead to death in a very short period if not brought under control. Even if the consequences are less dramatic, the patients' ability to lead a normal daily life is seriously impaired, and they may become severely depressed. SandostatinR alleviates the condition by inhibiting peptide release, and its long duration of action makes it an effective and rational adjunct to therapy at all stages. Last year a consensus Round Table Meeting was held in Scottsdale, Arizona, to discuss the optimal use of SandostatinR in this indication. These guidelines offer the results of clinical research and the dosage recommendations arising from them, together with a critical summary of the points of view presented.

Dr. Dobranowski and his associates are to be highly commended for this excellent manual. I am not aware of a similar text covering the subject. Although all of us perform gastrointestinal studies in a differ ent manner, this text provides an excellent overview. The reader will discover that the text is especially well written and focuses on the important issues relating to GI contrast studies. Because Dr. Steven son's group performs endoscopic procedures, they are included in the manual. These authors are recognized scholars and leaders in gastrointesti nal radiology. Thus, it is easy to understand why the manual is so well done. I am particularly impressed with the emphasis placed on the patient-radiologist relationship before, during, and after completion of a study. All of us who teach gastrointestinal radiology are concerned about the decline in the number of gastrointestinal contrast studies. We are not sure how we can continue to teach our residents the proper tech niques and maintain high-quality teaching programs in gastrointesti nal radiology. A manual of this type is thus timely and appropriate. The manual will be a valuable addition to the library of all radiologists. It will be particularly useful for residents who are learning how to per form GI contrast studies."

Vaccines have historically been considered to be the most cost-effective method for preventing communicable diseases. It was a vaccine that en abled global eradication of the dreaded disease smallpo. ."

This volume contains the papers presented at the International Symposium on "Cirrhosis, Hyperammonemia and Hepatic Encephalopathy," held in Valencia, Spain, De- cember 2nd_4th, 1996. Liver cirrhosis is one of the main causes of death in occidental countries. There are other hepatic dysfunctions such as fulminant hepatic failure, Reye's syndrome, or congenital deficiencies of urea cycle enzymes which can also lead to hepatic encephalopathy, coma and death. However, the molecular bases ofthe pathogenesis of hepatic encephalopathy remain unclear. One ofthe consequences of hepatic failure is the reduced ability to detoxify ammonia by incorporating it into urea. This leads to increased blood ammonia levels. Hyperam- monemia is considered one of the main factors responsible for the mediation of hepatic encephalopathy and classical clinical treatments are directed towards reducing blood ammo- nia levels. Altered neurotransmission is an essential step in the pathogenesis of hepatic encephalopathy. The first part of the book is devoted to the discussion of the recent advances in the understanding of the alterations of different neurotransmitter systems in hepatic encephalopathy. The alterations of tryptophan metabolism and neurotransmission in hepatic encephalopathy and the implications for the clinical use of neuropsychoactive drugs are reviewed. The alterations in glutamate transport and neurotransmission in hepatic encephal- opathy due to acute liver failure are also reviewed. The role of NMDA receptors in the molecular mechanism of acute ammonia toxicity is discussed as well as its modulation by metabotropic glutamate receptors and muscarinic receptors.

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.

Diagnostic Pathology of the Intestinal Mucosa - An Atlas and Review of Biopsy Interpretation offers a comprehensive overview of intestinal mucosal structure as defined through peroral or endoscopic biopsy specimens obtained in normal and disease states. It describes small intestinal biopsy pathology in conjunction with morphologic, functional, and pathophysiologic correlations. Routine methods of processing tissues for light microscopy, electron microscopy, histochemistry, and light- and electron- microscopic-immunoperoxidase techniques are presented so that the novice in the area of intestinal structure may have an easily accessible reference for setting up a morphologic laboratory.

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

This volume contains the papers presented in the International Summer Course on "Cirrhosis, Hyperammonemia and Hepatic Encephalopathy," which was one of the prestigious Summer Course, of the Complutense University of Madrid held in EI Escorial, Spain, during August 10-14, 1992. Liver cirrhosis is one of the main causes of death in western countries. In addition there is a series of liver dysfunctions including fulminant hepatic failure, Reye's syndrome and congenital defects of urea cycle enzymes that could lead to hepatic encephalopathy, coma and death. As a consequence of impaired liver function, the ability to detoxify ammonia by its incorporation into urea is diminshed, resulting in increased ammonia levels in blood and brain. Hyperammonemia is considered one of the main factors in the mediation of hepatic encephalopathy and the classical clinical treatments are directed towards reducing blood ammonia levels. A part of the book is therefore devoted to the study of certain aspects of ammonia metabolism such as the regulation of the urea cycle, the main mechanism of ammonia detoxification in mammals, which is located mainly in the liver. The metabolism of ammonia in other tissues, including brain, is also presented, as well as the effects of hyperammonemia on brain metabolism and function and on brain microtubules. The control of cerebral protein breakdown is reviewed. The classical and some recently proposed clinical treatments as well as nutritional considerations in the management of patients with liver failure are also discussed.

My training started in 1971, when I joined the First Department of Medicine of Chiba University, as Dr. Kunio Okuda became chair ofthe department. To acquire training ingeneralpathology, Iapplied for the Intern MatchingProgram and started as aninternin the DepartmentofPathologyofYale University, in 1973.While Iwas achiefresident, Ispent 10months in Dr. GeraldKlatskin'sofficestudyingthe com plete set of his famous liver biopsy samples (the Klatskin Collection). In 1976, I movedtoJohnWesleyHospital, where therewasagroup from the USC (University ofSouthern California) Liver Unit, to obtain further pathology training under the guidanceofDr. Robert L. Peters. Those experiences have given me ample opportu nity to see the differences between the United States and Japan. Ofcourse, 28 years ago in downtown Los Angeles there were enormous num bers ofpatients suffering from typical alcoholic liver diseases. Now in Japan, in contrast, we have an enormous number ofpatients suffering from hepatocellular carcinoma (HCC), due in particular to hepatitis C viral infection. Last year, in the DepartmentofGastroenterology at the University ofTokyo, we had approximately 500 admissions due to HCC. Thus, we have an urgent need to prevent the develop ment ofHCC and to provide better treatment for such patients through a basic un derstanding ofvirology, clinical features, and treatment modalities. The first single-topic conference on "TherapyofViral Hepatitis and Prevention ofHepatocellular Carcinoma" was organized by the Japan Society ofHepatology (Kiwamu Okita, Director General) and was held November 14-15,2002, near Mt. Fuji. Thisbook, which is asummaryofthe meeting, helps toupdate relevantinforma tion on this vital topic. June 28, 2003 Masao Ornata, M.D."

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.

This volume contains the papers presented at the International Symposium on "Cirrhosis, Hyperammonemia and Hepatic Encephalopathy," held in Valencia, Spain, January 24th-27th, 1994. Liver cirrhosis and other hepatic dysfunctions such as fulminant hepatic failure and congenital defects of urea cycle enzymes can lead to hepatic encephalopathy, coma and death. Hepatic encephalopathy is one of the main causes of death in western countries. The ability to detoxify ammonia by its incorporation into urea is diminished by impaired liver function, resulting in increased ammonia levels in blood and brain. Hyperammonemia is considered one of the main factors in the mediation of hepatic encephalopathy and the classical clinical treatments are directed towards reducing blood ammonia levels. However, the molecular bases of the pathogenesis of hepatic encephalopathy and the role of hyperammonemia in this process remain unclear and several hypotheses have been proposed. To clarify the mechanisms involved in hepatic encephalopathy and hyperammonemia suitable animal models are necessary. The animal models available and the ideal features of an animal model are presented in the initial part of the book.

Cancer is one of the major health problems of our time and liver cancer is responsible for over one million deaths per year world-wide, making it the fourth most common cause of death from cancer. Surgical resection of the tumour(s) is the treatment of choice and offers the only chance of prolonged survival. Yet the best attempts are often frustrated by either advanced or co-existent disease that renders the patient non-resectable. This book tackles the many options available to doctors and patients in an attempt to combat this desperate disease.

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.

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."

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."

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

This volume reviews a series of different publications dealing with orotic acid. Orotic acid was isolated from cow's milk 75 years ago by Biscaro and Belloni in Italy. Fifty years later again Italian scientists described the growth-promoting activity of orotic acid in vitamin B -deficient animals. 12 Orotic acid is the precursor of pyrimidine nucleotides which are involved in many biochemical reactions: UTP and CTP, as substrates for RNA polymerase, and UDP sugars, as substrates for carbohydrate containing macromolecules, e.g. glycogen, glycoproteins and glycolipids. The biosynthesis of these pyrimidines is well regulated. Disturbance of the biosynthetic pathway or trapping of individual pyrimidine nucleotides may lead to severe metabolic and structural alterations of cells. Synthesis, biochemical aspects and physiological role are reviewed in nine chapters. In the last two decades increasing interest in orotic acid came from several studies showing protective or therapeutic or beneficial effects of this compound in different kinds of organ injuries: various forms of hepatic insufficiency, myocardial infarction, encephalopathy, memorization pro cesses, mentioned in Chapters 8 and 9. At the end of this overview a Bibliography in an alphabetical order with 673 references may give further insight in this topic."

At the Mie International Symposium held in Japan in April 1994, leading scientists reviewed recent advances in the understanding of the contractile mechanism in smooth muscle. The present volume collects the papers presented at the symposium, summarizing the latest advances in smooth muscle function and emphasizing important components of the contraction-relaxation cycle. Topics include a discussion of the smooth muscle cell membrane, with emphasis on its ion channels; the regulation of cytosolic Ca2+ levels and the relationship to force in smooth muscle; aspects of the two key regulatory enzymes involved with myosin phosphorylation-dephosphorylation; the molecular basis for pharmacomechanical coupling in smooth muscle; developments in the basic contractile mechanisms involving the crossbridge cycle of tonic and phasic muscle; the role of myosin light chains; and many others. The approach is broad and presents contemporary opinions in pharmacology, physiology, and biochemistry as they relate to smooth muscle function. The book will appeal not only to those working in these disciplines, but to vascular clinicians, obstetric-gynecological physicians, and gastroenterologists as well.

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."

In this book, precursors of gastric cancer are described histopathologically, especially about the precancerous conditons and precancerous lesions of the stomach. In addition to those precancerous changes stated in previous monographs and textbooks, some newly recognized gastric dysplasias are proposed. In order to be able to ovjectively evaluate the atypism of dysplasic changes, achievements of morphometric studies were presented.

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."

This book deals with all aspects of surgery of the pancreas. The leading authorities from all over the world have contributed to this volume. Surgery of acute pancreatitis, chronic pancreatitis and pancreatic malignancies is demonstrated. This book defines standards for pancreaticand general surgeons. In addition all aspects of diagnostics, pathophysiology and basic scientific data with regard to pancreatic disease are presented.

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."