Bailliere's clinical gastroenterology最新文献

Biliary malignancies, including cancers of the intrahepatic and extrahepatic bile ducts, gallbladder and ampulla, should be considered in the differential diagnosis of patients with obstructive jaundice. Cancers of the intrahepatic bile ducts and ampulla are managed as liver and peri-ampullary tumours respectively. Extrahepatic bile duct cancers are diagnosed by cholangiography and evaluated for resectability by imaging and angiography. Vascular infiltration is the main contra-indication for resection, which may also involve the liver. Every attempt must be made to achieve curative resection, but local resection may be justified even if non-curative. Gallbladder cancers are usually advanced at the time of diagnosis and are unresectable—surgical palliation improves the quality of life by relieving biliary and gastric outlet obstruction. Long-term survival is possible after curative resection in early lesions that are usually diagnosed as an incidental finding after cholecystectomy for presumed gallstone disease. The role of adjuvant therapy in biliary malignancies needs further evaluation.

Disordered motility of the biliary tract may be associated with the aetiology of common biliary tract conditions, such as gallstones. In this instance, treatment of the gallstone disease alleviates symptoms in the majority of patients. However, in up to 10% of patients, biliary motility disorders may present in the absence of gallstones or in patients after cholecystectomy. Gallbladder dyskinesia results in biliary-type pain. This abnormality may be objectively identified using the radionuclide gallbladder ejection fraction. The majority of patients with an abnormal test are improved or cured following cholecystectomy. Sphincter of Oddi dysfunction presents with either recurrent biliary-type pain or recurrent pancreatitis. Manometry of the sphincter of Oddi objectively identifies patients with manometric stenosis. The majority of these patients are improved or cured following division of the sphincter of Oddi.

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease whose aetiopathogenesis is unknown. PSC is frequently associated with inflammatory bowel disease, in particular chronic ulcerative colitis, is most commonly observed in young males and is clinically characterized by fatigue, pruritus and jaundice. The diagnosis is supported by a cholestatic biochemical profile and histological abnormalities, and confirmed by visualization of an abnormal biliary tree. The natural history of the disease is currently being evaluated but is generally recognized to be slowly progressive, leading to complications of chronic cholestasis, portal hypertension and biliary cirrhosis. There is no specific medical treatment, and orthotopic liver transplantation remains the only definitive treatment for patients with end-stage PSC. A more rational approach to medical therapy will ensue upon a better understanding of the aetiopathogenesis of this disease.

The use of oral rehydration solution (ORS) with early refeeding forms the basis of therapy for dehydration secondary to diarrhoea. ORS has produced such positive results in dehydrated patients that no further scientific demonstration is needed to confirm its efficacy. This review presents several issues that remain unsettled or controversial. They include the following.

• 1.

  1. The mechanism of water handling by the intestine is discussed; this is more complex than initially thought, at the epithelial, cellular and molecular level.

• 2.

  2. The composition of ORS which has been successfully adapted for the most frequent conditions, except for severely malnourished children, is described.

• 3.

  3. In contrast to the strong scientific basis and obvious efficacy in rehydration of ORS, its consequences for growth, nutrition and mortality are difficult to demonstrate, unless adequate long-term nutritional support is also provided in addition to ORS.

• 4.

  4. Finally, discrepancies between the recommendations and the practice of oral rehydration therapy are now well documented. Analysis of the causes of these discrepancies may participate in improving public health campaigns.

Pathological processes and disease entities in the upper gastrointestinal (GI) tract, specifically those of the oesophagus and the stomach in infancy, have received a disproportionately small amount of attention until recently when appreciation of their pathophysiology and concordant importance in terms of symptomatology has been highlighted. This is probably a phenomenon secondary to improved diagnostic yield from the recent technical advances in areas such as infant endoscopy and a shift in opinion regarding the pathophysiological origin of ubiquitous symptoms of infancy such as feeding disorders, colic and irritability.

In addition, the apparently complex interactions of various aetiological factors such as pH-independent gastro-oesophageal reflux (GOR), cow's milk protein intolerance (CMPI), Helicobacter pylori gastritis and upper GI motor disorders have in the past 1–2 years become underlined in terms of aetiopathogenesis and have radically changed thinking regarding diagnosis and therapy of infants with apparent upper-GI-associated symptoms.

The contribution to comprehension of infant upper GI disorders of inflammatory paradigms and ontogeny of the upper GI tract is also a recent area worthy of mention. The recent advances in all of these areas and their contribution to the understanding, and subsequent diagnosis and therapy, of upper GI symptoms and their explanation by way of aetiopathogenesis will be explored in this chapter.

The aim of therapy in Crohn's disease in childhood is to induce and to maintain a remission of disease activity so that normal growth and development of the child may occur. Enteral nutrition may now be recommended as the first-line treatment for most children with Crohn's disease. However, the evidence for remission is better for children with Crohn's disease of the small intestine rather than of the large intestine. There is evidence that amino acid feeds (elemental), whole protein (polymeric) and. protein hydrolysate feeds (semi-elemental) may all be successful. Such a therapeutic approach can lead to healing of the mucosa and down-regulation of inflammation. However, in some cases surgery is required, particularly in children with growth failure and delayed puberty. Drug therapy also continues to have a role in therapy especially with severe colonic disease.

The intractable diarrhoeas of infancy present very major problems of clinical management. However, the conceptual importance of these conditions lies in the information that they may provide about normal small-intestinal function in humans: among such infants will be found the human equivalents of the ‘knock-out’ mice, in which targeted gene disruption allows sometimes unexpected insight into the regulation of intestinal function. The challenge posed by the intractable diarrhoeal syndromes, of working backwards from an apparently common phenotype to probably multiple genotypes, is, however, immense. Very few of these conditions have been described at the genetic level, although the molecular basis of pathogenesis has been better explored in recent years.

The two major groups of intractable diarrhoea are due to (1) primary epithelial abnormalities (which usually present within the first few days of life) and (2) immunologically mediated (which generally present after the first few weeks). The high prevalence of autoimmune enteropathy among infantile autoimmune disease, in contrast to adult autoimmunity, is intriguing and may reflect constitutive abnormality of extrathymic lymphocyte maturation. The use of potent immunosuppressive drugs and increasing expertise with parenteral nutrition are improving the outlook of these previously fatal conditions.

Viewed globally, however, the pressing problem is to treat effectively the millions of infants who die from severe persistent diarrhoea and wasting, which would certainly not be considered intractable in wealthy countries.

This chapter primarily concerns three main categories of diarrhoeagenic Escherichia coli, enteropathogenic (EPEC), enterohaemorrhagic (EHEC) and enteroaggregative (EAEC) E. coli. They have distinctive virulence factors and vary in the enteropathies they produce. The molecular biological approach has opened up the complex way in which they interact with the intestine. EPEC and EHEC show a subversive approach to colonization in that they adapt the host cell to their requirements in the formation of the attaching effacing lesion. EAEC appear to co-opt the host defence system to produce a biofilm-like colony and currently go unrecognized in routine laboratories.

Gene expression is central to the pathogenesis of many disorders. An ability to alter the expression of genes would, if their relationship to disease processes were fully understood, constitute a new modality of treatment. This review examines the evidence that nutritional factors can regulate genes in the gastrointestinal epithelium and it discusses the physiological relevance of such alterations in gene expression. Dietary regulation of the genes expressed by the epithelium confers three fundamental advantages for mammals. It enables the epithelium to adapt to the luminal environment to digest and absorb food better; it provides the means whereby mother's milk can influence the development of the gastrointestinal tract; when the proteins expressed by the epithelium act on the immune system, it constitutes a signalling mechanism from the intestinal lumen to the body's defences. Each of these mechanisms is amenable to manipulation for therapeutic purposes.

The term portal hypertensive gastropathy (PHG) defines a wide spectrum of diffuse macroscopic lesions that appear in the gastric mucosa of patients with portal hypertension. Histologically, these lesions correspond to dilated vessels in the mucosa and submucosa in the absence of erosions or inflammation. Endoscopically, the lesions are classified as mild when mosaic pattern or superficial reddening are present, and severe when gastric mucosa appear with diffuse cherry red spots. Mild lesions are highly prevalent (65–90%), whereas severe lesions are present in only 10–25% of cirrhotic patients.

The pathogenesis of PHG is not well known, but both venous congestion related with raised portal pressure and increased gastric blood flow seem to be crucial factors for its development. Variceal sclerosis may contribute to the development or aggravation of the lesions.

Bleeding is the unique clinical manifestation of PHG, and occurs only in those patients with severe lesions. During a 5-year follow-up, the risk of overt bleeding or chronic bleeding, which induces anaemia, is 60% and 90%, respectively, for patients with severe PHG.

Propranolol is the only pharmacological treatment that has been proven useful in preventing bleeding from PHG. Porto-systemic shunts and liver transplantation are also effective.