Over the 12 years since the first introduction of interferon for the treatment of chronic hepatitis B, progress has apparently been slow. Nevertheless, it now appears that at least one third of chronic hepatitis virus carriers, particularly those with more severe disease, and a similar, perhaps greater, proportion of those with chronic parenteral non-A, non-B hepatitis, can be successfully treated with alpha-interferon. In the not too distant future, controlled trials of alpha-interferons in these situations will be complete and they will be a yardstick by which other future therapies can be judged. Already a number of trials are in progress to determine which agents might, in addition to interferon, augment the response rates. The situation clinically is analogous to that for tuberculosis in the 1950s and for cancer chemotherapy only a decade or so ago. The prospects of prevention of the progression to cirrhosis, and perhaps in the long term reduction in the incidence of hepatocellular carcinoma, are exciting, and with the introduction of a number of new cytokines available through recombinant technology, each with novel antiviral activities, the future prospects are exciting indeed.

There are now many types of liver resection, depending on the amount of liver to be resected and the surgical technique selected. In the field of anatomical surgery the surgeon can choose between a major or a lesser hepatectomy and between preliminary ligation of the vessels or a primary parenchymatous resection. Sound knowledge of the anatomy is a prerequisite for anatomical surgery of this organ. Although confusion has existed as a result of differences in the nomenclature of the functional anatomy of the liver, we believe that the numerical segmental description of Couinaud is the most accurate and most easily understood. Operative ultrasonography has a fundamental role in liver surgery. It supplements information obtained by intensive preoperative investigations and enables the surgeon to make more precise and limited resections than were previously possible. It provides a greater range of options in the management of hepatocellular carcinoma. The surgeon confronted with a malignant tumour of the liver should base his decision for resection on the tumour characteristics: primary or secondary, extra- or intrahepatic spread, position, histological differentiation and presence or absence of cirrhosis. Anatomical resections should be performed providing good tumour clearance margins, while preserving as much functional parenchyma as possible. Supplementary therapies such as arterial ischaemia and chemotherapy should always be considered, but it must be borne in mind that at present hepatic resection offers the only hope of cure for malignant hepatic tumours.

The focus of the nutritional management in liver disease has swung from micronutrients with the supplementation of vitamins back to the problems of the macronutrients and especially the importance of protein metabolism. Whether the considerable activity in this area in the last few years, particularly in patients with acute alcoholic hepatitis, will result in significant improvements not only in the overall medical management and consequently the quality of life, but also on life itself, still remains to be seen.

To assess the reported association between colonic angiodysplasia and aortic stenosis, we performed a quantitative and methodologic analysis of the literature. In four controlled studies that support an association between aortic stenosis and idiopathic gastrointestinal bleeding there are major methodologic deficiencies including the following: nonblinded data collection, noncomparable diagnostic examination, nonblinded ascertainment of exposure, and noncomparable demographic susceptibility. None of the studies directly assesses angiodysplasia. Additional case reports about aortic valve replacement used to treat bleeding from angiodysplasia are limited in number and in duration of follow-up. We conclude that the existing literature does not demonstrate an association between aortic stenosis and angiodysplasia. Further controlled evaluation of this topic would be useful.

This report analyzes the literature on sphincter of Oddi dysfunction as it applies to biliary-type pain. The sensitivities and specificities of the tests used to diagnose this condition (e.g., size of bile duct, drainage time of bile duct, provocative tests with morphine, sphincter of Oddi manometry) are poorly defined. Recent studies suggest that noninvasive tests such as quantitative nuclear scintigraphy and fatty meal sonography may aid in diagnosing functional common bile duct obstruction. Continuous manometry of the biliary tree with microtransducer technologies may allow a greater understanding of the causes of pain in this group of patients. Only 1 case report of pharmacologic management for this disorder exists in the literature. Endoscopic sphincterotomy may be helpful in relieving the pain that occurs in this condition but is associated with increased risks. There is no consensus in the literature as to the best test that will predict response to sphincterotomy. Controlled trials of medical therapies are needed.

The physiological control of muscle protein balance has been reviewed. In addition to trauma, fasting and reduced activity have been shown to cause muscle protein loss through changes in synthesis and breakdown. Many of the effects of these states are mediated by alterations in the concentrations of insulin, glucagon, steroids and catecholamines. Branched-chain amino acids also appear to have specific effects in improving protein synthesis. Recently, prostaglandins have been identified as having a central role as mediators in the control of protein metabolism by many hormones and pathological states. Identification of factors which control muscle protein synthesis leads to the possibility that the metabolic response to illness and injury and its attendant muscle protein loss could be open to pharmacological manipulation. Inhibition of prostaglandin synthesis by non-steroidal anti-inflammatory drugs can improve muscle protein turnover, but their clinical usefulness may be limited by side-effects. Hormonal manipulation may offer the possibility of abolishing the metabolic response. For example, inhibition of adrenal secretion in surgical patients by spinal anaesthesia appears to modify many of the metabolic effects of injury. A variety of other treatments have been used to minimize the metabolic derangements of injury. Some of these have considerable potential, but as yet clinical benefits from their use have not been positively identified. It is likely that a pharmacological approach to the nutritional disorders of stress and injury will prove to be of major interest in the future.

Home parenteral nutrition services have revolutionized the treatment, and improved the survival, of patients with prolonged or permanent intestinal failure. Without such a programme, these patients either would be condemned to continuous in-patient parenteral nutrition or to death. The indications for HPN in the UK remain predominantly intestinal failure resulting from inflammatory bowel disease, and major small bowl resection. Nearly 50% of patients receiving HPN will ultimately have normal intestinal function restored and thus be able to return to enteral feeding. This knowledge is reflected in the selection criteria for instituting HPN. The use of HPN in patients with malignant disease poses significant ethical questions. The success of HPN is dependent upon the organization of nutritional units to allow centralization of HPN programmes and to provide the necessary support to patients. It is clear that not all patients will benefit from HPN, and it is only by careful assessment of patients, based on the experience of specialized nutritional units, that a rational HPN service can be provided.

Abnormal values of parameters generally associated with description of protein or energy stores are often observed in cancer patients. The aetiology of these abnormal values is not clear, but seems to include insufficient energy intake absolutely (anorexia), or relative to energy needs (increased energy expenditure). In addition, the ability of some tissues to acquire nitrogen and energy seems to be changed when cancer is present. The resulting status described by abnormal values of protein or energy store parameters is often incorrectly referred to as malnutrition. Incorrect because many factors other than nutrition are related to the development of this condition. However, the presence of the so-called malnutrition is associated with increased morbidity, decreased survival and decreased tolerance to cancer therapy. Whether nutritional therapy is able to reverse these adverse effects by malnutrition remains unproven: most trials performed in an attempt to prove such restoration of the individual's ability to withstand cancer and its treatment, display such conceptual flaws that a convincing answer cannot be given. On the other hand, a deleterious effect of nutritional support has not been observed. More, and clinically relevant, research needs to be performed in this field.

Enteral nutrition is only part of the wider field of clinical nutrition in which great advances in both theory and practice have been made over the last decade. We have attempted to summarize what we consider to be the advances that have most relevance to the clinical practice of enteral nutrition. This chapter reviews our present understanding of the processes of digestion and absorption of protein, carbohydrate and fats, and examines how this theoretical understanding can be applied to patients in the clinical situation. A broad classification of the different enteral diets is undertaken, and the reasons for the development of particular diets are discussed. The clinical value of these diets is assessed. The wide variety of indications for enteral (as opposed to parenteral) nutrition are discussed and the specific benefits of enteral nutrition for the patient are highlighted. Techniques of administration of enteral nutrition are reviewed in detail, and the methods by which enteral nutrition should be monitored are outlined. Finally, complications of enteral nutrition are summarized and advice given on how to prevent or treat them.

The assessment of protein-energy malnutrition has become important for identifying patients whose nutritional status increases their risk of an adverse outcome during hospitalization. Anthropometric, biochemical and immunological measurements, used either alone or in combination are not sensitive or specific enough for monitoring short-term nutritional changes, although some of these variables are associated with an increased incidence of postoperative complications after surgical procedures. The sensitivity of clinical assessment is dependent on the training of the clinician and the outcome variable being sought. For most clinicians, objective measurements are needed to raise their awareness to potential nutritional problems. The relationship of nutritional status to clinical events, particularly stress events during hospitalization, is critical to the interpretation of nutritional measurements and relating them to outcome variables. A classification based on the concepts of nutritional depletion and stress is presented. The prevalence of PEM has been shown to be between 20 and 30% in western hospitals, depending on the population studied and the criteria used to define PEM. In studies which have claimed an association between nutritional status and outcome, the contribution of nutritional variables to the development of postoperative complications has been overestimated and the relevance of technical factors underestimated.

The altered energy metabolism and substrate requirements of tumour cells can provide a target for selective antineoplastic therapy. The supply of substrates for tumour energy metabolism can be reduced by dietary manipulation (e.g. ketogenic diet) or by pharmacological means at the cellular level (e.g. inhibitors of glycolysis or oxidative phosphorylation). Both these approaches are examined with a view to the development of selective and therefore non-toxic methods of controlling tumour growth in vivo.

The existence of a co-ordinated response to stress of a variety of causes has clearly been established. Basically, this consists of an elevation in energy expenditure and an increased breakdown of skeletal muscle protein. In addition, glucose level in the plasma increases as a result of increased synthesis and decreased uptake of glucose into cells. Release of fatty acid into the plasma is also increased, and an elevation in the proportion of energy derived from oxidation of fatty acids is observed. This response is qualitatively very different from that seen in simple starvation, where a progressive reduction in energy expenditure and a reduction in the synthesis of glucose allows fat to become the major energy-producing substrate and also allows sparing of body protein stores. The mechanisms responsible for this altered pattern of metabolism are probably primarily hormonal in nature, with adrenaline, cortisol and glucagon being the major catabolic stimulants. Some evidence exists, however, for alteration in intracellular pathway metabolism. Within the past decade a new class of mediators of the stress response, the cytokines, has been recognized. These substances are protein products of circulating monocytes and the way in which they integrate into the control of the stress response has not been completely elucidated. At present there is evidence that they can stimulate production of catabolic hormones, and also they may well have direct effects in enhancing protein catabolism in muscle. At present the main method for modification of the stress response remains the provision of energy and amino acid, either intravenously or enterally. In the present state of our knowledge, 30-40 kcal kg-1 day-1 would appear to be adequate for most patients, with half provided as fat. Amino acids 3 g kg-1 day-1 will provide adequate nitrogen. It must be said, however, that the most effective method of modifying the stress response is removal of the source of stress by surgery, antibiotics or other primary therapy.

An adequate provision of all micronutrients, vitamins and essential trace elements is necessary for maintenance of normal tissue function. In patients requiring nutritional support, these factors are essential for optimal utilization of the major nutrients and play a role in all aspects of intermediary metabolism. In this chapter, some of the main features of the micronutrients have been described, together with suggestions regarding their provision enterally or parenterally. For most of these nutrients, diagnostic methods are not available to permit accurate assessment of status and hence the level of provision necessary for optimal results. However, there is now sufficient understanding of nutritional requirements such that few patients should now develop clinical or biochemical signs of under- or overprovision of micronutrients.