Bailliere's clinical gastroenterology最新文献

Active Crohn's disease constitutes a major problem in gastroenterology. Symptoms vary with site, extent and local complications of the disease as well as with the absence or presence of extraintestinal manifestations. Due to the troublesome consequences of the disease new treatments have continuously been tried. However, the results have varied and no definite breakthrough has occurred in the medical treatment of active Crohn's disease during the last years. The new salicylates have shown some effect using higher doses, but have not fulfilled the expectations once connected with their development. The new steroids have compared well to, but not exceeded, the older corticosteroid preparations in terms of therapeutic efficacy but they have a better side-effect profile. The role of the purine analogs azathioprine/6-mercaptopurine has been further evaluated. The onset of their effect is slow, an intravenous loading dose might shorten this time span, and they are steroid sparing. The controlled data on methotrexate are limited and the long-term effects not well studied and there is concern about toxicity. Even the use of cyclosporine in active Crohn's disease is controversial and connected with serious adverse events. Studies on the new immune modulating therapies such as anti-TNF-ct antibodies, anti-CD4 antibodies, interleukin-10 and interferon have been encouraging but large scale studies are still awaited before the effect and the spectra of side-effects can be fully evaluated.

The aim of this chapter is to summarize the present knowledge of medical treatment of active Crohn's disease and to point towards the directions of new therapeutic options.

This chapter reviews the current state of imaging in Crohn's disease. Imaging plays an important role in the diagnosis and management of Crohn's disease. Imaging is complementary to the clinical assessment of the patient and other investigations including endoscopy. The choice of imaging modality depends on the clinical circumstances and local availability of resources and skills. Close co-operation between clinicians and radiologists is important. Barium radiology remains important. Magnetic resonance imaging (MRI) and ultrasound (US) should get special consideration because of the lack of ionizing radiation. MRI is particularly good at demonstrating the perianal complication of Crohn's disease. Computer tomography (CT) and US can be used for image-guided drainage of abscesses.

Despite recent advances in the medical therapy of Crohn's disease, surgery continues to play a central role in the treatment of the disease. The strategy for surgical management of Crohn's disease continues to evolve. This chapter reviews many of the controversies surrounding surgical palliation of complications of Crohn's disease. Included is a discussion of indications for strictureplasty in treatment of intractable intestinal obstruction. Factors influencing long-term outcome with sphincter-saving resection in the treatment of Crohn's colitis are reviewed. Experience with definitive treatment of anal Crohn's disease and repair of rectovaginal fistulas is examined. Finally, recent experience supporting ileocolic resection when acute Crohn's ileitis is identified during laparotomy for right lower quadrant pain is critically evaluated. These controversial aspects of the surgical treatment of Crohn's disease reflect an improved understanding of the natural history of the disease as well as refinement in surgical techniques and better definition of criteria for surgical intervention.

In the absence of a single initiating aetiological factor, most workers envisage Crohn's disease as the manifestation of poorly regulated immune and inflammatory processes within the gut wall. Initially these responses may arise as a response to common antigens associated with the gut—bacterial products being amongst the most obvious candidates. In genetically predisposed individuals there is overexpression both of local immune response mechanisms in the gut wall (T-cells, B-cells and macrophages) and of systemic inflammatory cells (predominantly polymorphonuclear leukocytes), which are attracted into the inflamed gut through activation of adhesion molecules on the vascular endothelium. As a consequence a large number of pro-inflammatory processes are expressed in the gut wall, inadequately checked by the normal counter-inflammatory processes that should serve to limit inflammation. Defining the relative importance of the individual processes, and identifying critical steps that could be inhibited or enhanced for therapeutic purposes, is a major challenge of Crohn's disease research.

Disordered nutrition is common in Crohn's disease and is multifactorial. Regular and systematic monitoring of at least a minimum set of nutrition data is an essential component of care of children and adults with Crohn's disease. However, even in children, monitoring of growth and development may be deficient. Multiple macro- and micronutrient deficiencies are common in Crohn's disease, especially in those with extensive small bowel deficiencies or after multiple surgical resections. Body composition analysis may show differences from simple starvation, and metabolic effects of inflammation are increasingly being recognized. Nutritional support is part of the management of all patients with Crohn's disease, but nutritional intervention with defined formula liquid diet is an effective specific anti-inflammatory therapy.

Although meta-analysis of published trials suggest that steroids are more effective than defined formula liquid diets, objective evidence from whole gut lavage fluid analysis and from faecal excretion of radiolabelled leukocytes shows unequivocal benefit of elemental diet based on measuring parameters of tissue damage. Enteral feeding with liquid diets should be considered in patients with incomplete small bowel obstruction, severe painful perianal disease, failure of corticosteroids in active Crohn's disease, borderline intestinal failure and in children with active Crohn's disease or with growth failure.

Patients with Crohn's disease are haunted by the likelihood of recurrence following resection of their disease. In an effort to better counsel patients about their relative risk, many centres have evaluated a myriad of factors thought to be harbingers of recurrence. Insightful review of the numerous studies requires consideration of the definition of recurrence, length and manner of follow-up, and statistical tools used for analysis of the data. Factors that may possibly influence recurrence include: age of disease onset; gender; tobacco use; anatomical pattern of disease; clinical pattern of disease; extra-intestinal manifestations; duration of pre-operative symptoms; previous resections; operative indication; blood transfusion; extent of resection; faecal diversion; pathological features of resected bowel; and chemotherapy following resection. Unfortunately, the role that these factors play in disease recurrence remains poorly understood.

Laparoscopic surgery for patients with Crohn's disease is feasible and safe. It may be conducted in appropriately selected patients including those with localized abscess, phlegmon, simple intra-abdominal fistulas, and perianastomotic recurrent disease. However, as the technique is just evolving and has yet to be shown to be of advantage over conventional open surgery, it should not be considered as a standard care. Randomized prospective clinical studies are needed to determine that laparoscopic surgery for Crohn's disease is at least equivalent or better than conventional open surgery.

About 90% of patients with Crohn's disease require surgery at some time in their lives but the clinical recurrence rate after surgery is about 50% within 5 years, with 50% requiring further surgery within 10 years. Endoscopic evidence of relapse can be found in 75% within 12 weeks of resection. There is therefore a major problem to be solved. The solution is less clear. Retrospective studies suggest that smoking is a major factor determining a poor prognosis after surgery and it is most important that patients are encouraged to stop. There is strong evidence linking diet with Crohn's disease but the mechanism and nature of this link remains unclear. A low total fat intake, possibly supplemented with eudragitcoated n-3 fatty acid (fish oil) looks reasonable on current evidence but not proven.

Mesalazine and metronidazole are the drugs for which most supportive evidence is available. The individual trials of mesalazine have generally proved inconclusive and meta-analyses have been needed to demonstrate a significant beneficial effect (approximately halving the relapse rate at 1 year). More recent large controlled studies performed after the meta-analyses however have again proved negative and the benefit is probably more modest than the meta-analyses suggested. Metronidazole, 20 mg/day for the first 3 months after surgery, has been shown to reduce relapse by just over one-third with a beneficial effect that was surprisingly sustained throughout a 3 year follow-up period. Peripheral neuropathy is a problem and further studies are needed at lower dosage. Azathioprine, 1.5-2 mg/kg/day is effective as maintenance therapy but there is insufficient evidence to recommend its routine post-operative use, moreover it takes up to 3 months to have an effect. Although budesonide has been shown to delay the time to relapse in nonoperated patients it, like other corticosteroids, has been shown to be no better than placebo when maintenance is assessed according to the proportion of patients who remain relapsefree after 1 year.

Patients undergoing operation for Crohn's disease should therefore be strongly advised to stop smoking. A 3 month course of oral metronidazole plus continued maintenance with oral mesalazine can be justified on current evidence but further studies are needed.