Bailliere's clinical gastroenterology最新文献

The role of diet in the aetiology and pathogenesis of ulcerative colitis (UC) remains uncertain. Impaired utilization by colonocytes of butyrate, a product of bacterial fermentation of dietary carbohydrates escaping digestion, may be important. Sulphur-fermenting bacteria may be involved in this impaired utilization. Oxidative stress probably mediates tissue injury but is probably not of causative importance. Patients with UC are prone to malnutrition and its detrimental effects. However, there is no role for total parenteral nutrition and bowel rest as primary therapy for UC. The maintenance of adequate nutrition is very important, particularly in the pen-operative patient. In the absence of massive bleeding, perforation, toxic megacolon or obstruction, enteral rather than parenteral nutrition should be the mode of choice. Nutrients may be beneficial as adjuvant therapy. Butyrate enemas have improved patients with otherwise recalcitrant distal colitis in small studies. Non-cellulose fibre supplements are of benefit in rats with experimental colitis. Eicosapentaenoic acid in fish oil has a steroid-sparing effect which, although modest, is important, particularly in terms of reducing the risk of osteoporosis, but it seems to have no role in the patient with inactive disease. γ-Linolenic acid and anti-oxidants also are showing promise. Nutrients may also modify the increased risk of colorectal carcinoma. Oxidative stress can damage tissue DNA but there are no data published at present on possible protection from oral anti-oxidants. Butyrate protects against experimental carcinogenesis in rats with experimental colitis. Folate supplementation is weakly associated with decreased incidence of cancer in UC patients when assessed retrospectively. Vigilance should be maintained for increased micronutrient requirements and supplements given as appropriate. Calcium and low-dose vitamin D should be given to patients on long-term steroids and folate to those on sulphasalazine.

There is now considerable evidence that abnormalities of the structure and function of the colonic epithelium are present in patients with ulcerative colitis and that many of these may occur independently of mucosal inflammation. It is proposed that epithelial abnormalities are the central defect that underlie the development of mucosal inflammation and its chronicity. A simple model for pathogenesis is proposed in which inflammation develops only when epithelial barrier function is impaired to an extent which permits the influx of luminal pro-inflammatory molecules to the lamina propria. Several candidate hypotheses regarding the molecular basis for the abnormality are addressed. The mechanism by which the barrier function is critically impaired involves the interaction of the abnormal epithelium with luminal, mucosal and systemic factors. Focusing on the epithelium would potentially lead to a conceptually different management approach and the development of novel therapeutic strategies.

The majority of patients with ulcerative colitis (UC) will run a typical chronic, relapsing course. The proportion with chronic, continuous symptoms diminishes with time. The greatest impact of the disease is in the first few years after diagnosis, especially in patients with extensive or severe colitis. After this time, the likelihood of requiring surgery declines rapidly, and survival is no different from that of the general population. The long-term course can be best predicted by the course in the preceding period. Most patients are able to lead an essentially normal lifestyle, at work and at home, with either medical or surgical treatment. Awareness of how the patient feels the disease affects his or her life is important. Educating the patient about their illness will also help in management.

Topical therapy can be considered the standard treatment for distal ulcerative colitis. The group of drugs of first choice are the aminosalicylates which are effective in inducing remission in acute disease as well as in preventing relapse. Corticosteroids appear to be slightly less effective and have no proven benefit in maintenance therapy. With new topical steroids, such as budesonide, systemic effects can be minimized. The major role of corticosteroids is to complement aminosalicylates, when necessary. The new topical compounds appear to be especially valuable when there is a long-term requirement for corticosteroids. With the vast majority of patients obtaining remission with standard treatment, it is difficult to make the case for alternative substances. Short-chain fatty acids, local anaesthetics and bismuth compounds seem to be the most promising innovations in topical therapy although their equivalence or even superiority to mesalazine has not been established.

Ileal pouch-anal anastomsis (IPAA) has become the operation of choice following protocolectomy for ulcerative colitis (UC) and familial adenomatous polyposis. Functioning ileal pouch mucosa undergoes histological changes resembling the colon (colonic metaplasia). The possible role of stasis and luminal factors—bile acids, short-chain fatty acids and bacteria—are discussed. It seems likely that colonic metaplasia is an adaptive response to the new luminal environment in IPAA. Inflammation in the ileal reservoir (‘pouchitis’) is the most significant late complication in IPAA. It occurs in 20–30% of patients and is virtually confined to those with prior UC. The clinical picture in pouchitis is highly variable; however, it can be easily categorized into three groups. Nevertheless, in most cases it is likely to represent recurrent UC in the ileal pouch. Current treatments and possible preventative strategies for pouchitis have been outlined.

The place of colonoscopy in the management of ulcerative colitis is restricted to clinical situations where the information provided will change clinical management. The information provided will be answers to the questions ?inflammatory bowel disease, or, in the patient with known colitis: inflammatory bowel disease ?type ?activity ?extent ?dysplasia. Biopsy is pivotal to the diagnosis and provides the certainty of tissue diagnosis, assessment of activity and detection of dysplasia. p]Sigmoidoscopy is sufficient for providing information for clinical management in most circumstances, but colonoscopy is important where clinical features are disproportionate to sigmoidoscopic findings and systemic parameters of inflammatory activity; to determine type and extent of inflammatory bowel disease and when surveillance needs to start; and for biopsy to detect dysplasia. Ileoscopy is an important aspect of colonoscopy for differential diagnosis, and is the unique definer of total colonoscopy.

Ulcerative colitis is an inflammatory disease of the large intestine of unknown aetiology. The nature of the inflammatory infiltrate together with the response to corticosteroids suggests that an abnormal immune response is at work. The key question of whether the immune system is responding to an abnormal breach in the mucosa due to another primary abnormality or whether the primary defect lies within the immune response itself has not been answered. Thus far, it is clear that both T and B cell compartments are involved in the persistence of inflammation but the initial interactions that take place in the mucosa in terms of antigen processing and presentation have not been adequately investigated. Those critical steps and potential defects that push T cells and B cells into a heightened state of activation need to be identified.

Neuroendocrine tumours can form in any part of the gastrointestinal tract. The most common types are the ECL cell tumours of the oxyntic mucosa of the stomach, G cell tumours of the duodenum, argentaffin, EC cell tumours of the small intestine and L cell tumours of the large bowel. The only well-defined clinical syndromes associated with hormone hypersecretion are ZES, resulting from duodenal gastrinomas, and carcinoid syndrome, caused by malignant argentaffin tumours. Genetic predisposition has been demonstrated for some tumour types, e.g. duodenal gastrinoma in MEN 1 and duodenal somatostatin cell tumours in MEN 2. Other factors predisposing to the genesis of these lesions include circulating hormone levels and the maintenance of chronic inflammatory states. As with most neuroendocrine tumours, malignant potential is difficult to assess on the basis of histology alone and prognostic evaluation depends more on size and evidence of local invasion and/or distant metastases.

With the introduction of longer-acting somatostatin analogues symptomatic relief is easy to achieve in patients with functionally active endocrine tumours and will be further facilitated by still longer-acting formulations. The consequences of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome can be prevented by all proton-pump inhibitors currently on the market.

Despite the various antiproliferative strategies that have been offered to patients with metastatic disease, available data are controversial and, more importantly, are supported by few prospective and controlled studies. Most experts agree that surgery with curative extirpation of the primary in the absence of metastases and tumour debulking in metastatic disease should be intended wherever possible. Controversy concerns residual disease. According to our view, any further antiproliferative strategy should consider the growth characteristics and biology of a given tumour (Figure 4). In the case of rapid progression, chemotherapy should be offered if tumours originate from the pancreas or reveal an undifferentiated histology. In contrast, chemotherapy should not be offered to patients with well-differentiated non-functional or functional tumours (carcinoid syndrome) arising from the intestine. The same applies for patients with tumours with no or only slow growth within an given observation period of 3–12 months. These patients should be treated only symptomatically.