Role of endoscopic endoprostheses in proximal malignant biliary obstruction.

The management of hilar strictures is dependent upon their resectability and may therefore require a multidisciplinary approach. However, resectability rates for such tumors are reported to be in the region of 15%-20%, and, therefore, palliative therapy will be the mainstay of treatment for most patients. With the presenting symptoms being those of obstructive jaundice and the consequences of cholestasis, a significant improvement in morbidity can be obtained by achieving biliary drainage. A number of options are available, including the placement of Teflon or expandable metallic endoprostheses by either the endoscopic or percutaneous route. Some considerable debate exists as to which route of stent placement is best, and in many circumstances the decision will depend on the availability of local services. Some have suggested that success rates with percutaneous stenting are superior to those for endoscopic placement, but the latter technique may be associated with fewer complications. In competent hands, endoscopic placement does achieve a high rate of success and it should be remembered that a combined approach may further improve success rates. The debate over the use of plastic versus metallic stents is centered around the higher rates of stent occlusion/migration for plastic stents seen in some studies, although a stent change is usually possible. An additional advantage of metallic stents is that they may provide drainage of the side branches of the biliary tree through the mesh. However, possible drawbacks may be a greater difficulty in placement of a second stent where a first provides inadequate drainage, and cost issues often have to be taken into consideration. Considerable debate exists over the optimum number of stents required to achieve adequate drainage and minimize the risks of cholangitis. There is good evidence that if overfilling of the biliary tree with contrast is avoided with only the segments to be drained visualized, a single stent may be all that is required, while others argue that placement of more than one stent may improve survival. In the following review we discuss these issues, and conclude by considering success rates and complications following endoprosthesis insertion; we also discuss the prognosis of patients treated in this way.

Non-invasive investigation of inflammatory bowel disease.

The assessment of inflammatory activity in intestinal disease in man can be done using a variety of different techniques. These range from the use of non-invasive acute phase inflammatory markers measured in plasma such as C reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) (both of which give an indirect assessment of disease activity) to the direct assessment of disease activity by intestinal biopsy performed during endoscopy in association with endoscopic scoring systems. Both radiology and endoscopy are conventional for the diagnosis of inflammatory bowel disease (IBD). However these techniques have severe limitations when it comes to assessing functional components of the disease such as activity and prognosis. Here we briefly review the value of two emerging intestinal function tests. Intestinal permeability, although ideally suited for diagnostic screening for small bowel Crohn's disease, appears to give reliable predictive data for imminent relapse of small bowel Crohn's disease and it can be used to assess responses to treatment. More significantly it is now clear that single stool assay of neutrophil specific proteins (calprotectin, lactoferrin) give the same quantitative data on intestinal inflammation as the 4 day faecal excretion of 111Indium labelled white cells. Faecal calprotectin is shown to be increased in over 95% of patients with IBD and correlates with clinical disease activity. It reliably differentiates between patients with IBD and irritable bowel syndrome. More importantly, at a given faecal calprotectin concentration in patients with quiescent IBD, the test has a specificity and sensitivity in excess of 85% in predicting clinical relapse of disease. This suggests that relapse of IBD is closely related to the degree of intestinal inflammation and suggests that targeted treatment at an asymptomatic stage of the disease may be indicated.

Fecal calprotectin as an index of intestinal inflammation.

The assessment of inflammatory activity in intestinal disease in man can be done using a variety of different techniques, from measurement of conventional noninvasive acute-phase inflammatory markers in plasma (C-reactive protein and the erythrocyte sedimentation rate) to the direct assessment of disease activity by intestinal biopsy. However, most of these techniques have significant limitations when it comes to assessing functional components of the disease that relate to activity and prognosis. Here we briefly review the value of a novel emerging intestinal function test, fecal calprotectin. Single stool assay of neutrophil-specific proteins (calprotectin, lactoferrin) give the same quantitative data on intestinal inflammation as the 4-day fecal excretion of indium-111-labeled white cells. Elevated levels of fecal calprotectin have been demonstrated in patients with NSAID-induced enteropathy and have been used in the diagnosis of colorectal cancer. Fecal calprotectin is increased in over 95% of patients with inflammatory bowel disease (IBD) and correlates with clinical disease activity. It reliably differentiates between patients with IBD and irritable bowel syndrome (IBS). More importantly, at a given fecal calprotectin concentration in patients with quiescent IBD, the test has a specificity and sensitivity in excess of 85% in predicting clinical relapse of disease. This suggests that relapse of IBD is closely related to the degree of intestinal inflammation and suggests that targeted treatment at an asymptomatic stage of the disease may be indicated. (c) 2001 Prous Science. All rights reserved.

Comparison of the intestinal toxicity of celecoxib, a selective COX-2 inhibitor, and indomethacin in the experimental rat.

BACKGROUND: It is suggested that the gastrointestinal toxicity of conventional non-steroid anti-inflammatory drugs (NSAIDs) is due to a 'topical' effect in addition to inhibition of the mucosal constitutive cyclo-oxygenase-1 (COX-1) enzyme. COX-2 selective inhibitors have been shown to have excellent gastrointestinal tolerability, but it is not known whether this is due to their selectivity and/or a lack of a 'topical' effect. We assessed the effects of celecoxib (a highly selective COX-2 inhibitor) on key pathophysiologic events in NSAID enteropathy. METHODS: The 'topical' effects of indomethacin and celecoxib were assessed in vitro (coupled mitochondrial respiration) and in vivo (mitochondrial electron microscopy) and the consequences by study of intestinal permeability (51-Cr-labelled ethylenediamine-tetraacetic acid urinary excretion) and inflammation. We also assessed intestinal prostanoid levels (prostaglandin E, PGE) and the propensity of the drugs to induce intestinal ulcers. RESULTS: Indomethacin uncoupled mitochondrial oxidative phosphorylation in vitro and in vivo, caused a significant (P < 0.0001) increase in intestinal permeability, caused mucosal inflammation and a 90% decline in intestinal PGE levels, and was associated with multiple small intestinal ulcers. Celecoxib caused no significant increase in any of these parameters, did not decrease intestinal PGE levels, and caused no intestinal ulcers. CONCLUSIONS: The intestinal tolerability of celecoxib appears to be due to a combination of the absence of a 'topical' damaging effect and selective COX inhibition.

Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease.

BACKGROUND & AIMS: Prediction of relapse of inflammatory bowel disease has important implications for therapeutic strategies. We assessed whether measurement of intestinal permeability and inflammation could predict relapse of inflammatory bowel disease (IBD). METHODS: Forty-three patients with Crohn's disease (CD) and 37 with ulcerative colitis (UC) in clinical remission provided a stool sample to be assayed for calprotectin (a neutrophil-specific marker), and patients with CD additionally underwent a small intestinal permeability test. Relapse was defined using clinical disease activity indices. RESULTS: Twenty-five (58%) patients with CD and 19 (51%) with UC had a relapse over the 12-month period. Median calprotectin levels in the relapse groups (122 mg/L for CD, 123 mg/L for UC; normal <10 mg/L) differed significantly (P<0.0001) from those of the nonrelapse groups (41.5 mg/L for CD, 29.0 mg/L for UC). At 50 mg/L, the sensitivity and specificity of calprotectin for predicting relapse in all patients with IBD were 90% and 83%, respectively. Permeability in the CD patients who relapsed (median, 0.075; normal <0.04) differed significantly (P = 0. 004) from that in the nonrelapse group (median, 0.038). At the level of 0.05, the sensitivity and specificity of permeability in predicting relapse were 84% and 61%, respectively. CONCLUSIONS: Fecal calprotectin predicts clinical relapse of disease activity in patients with CD and UC, whereas small intestinal permeability is a useful predictor of relapse in patients with small intestinal CD.

The effects of a preassessment clinic on nonattendance rates for day-case colonoscopy.

BACKGROUND AND STUDY AIMS: Nonattendance for colonoscopy contributes to an increase in the waiting lists for this procedure. Preassessment clinics routinely run for a number of day-patient surgical procedures have been shown to reduce nonattendance rates by enhancing patient understanding. This study aimed to determine prospectively whether preassessing patients booked for colonoscopy would lead to a reduction in the nonattendance rate. PATIENTS AND METHODS: Nonattendance rates for colonoscopy were assessed in consecutive 9-month periods. During the first period all patients were mailed appointments for colonoscopy with dietary and purgative bowel preparation instructions. During the second period, patients who had never previously undergone a colonoscopic examination were invited to attend a preassessment clinic, while patients who had attended for colonoscopy in the past were sent appointments and purgative instructions in the post. RESULTS: 344 colonoscopies were booked in the first 9-month period and 350 in the second, of which 195 were preassessed. Overall, 60 patients did not attend for colonoscopy during the first 9-month period (17.4%), and 40 (11.4%; P<0.05) did not attend during the second period of study. During the second 9 months only six (3.1%) of the 195 preassessed patients did not attend for colonoscopy, in comparison with 34 (22%; P<0.0001) of the 155 patients not preassessed. CONCLUSIONS: By running a limited preassessment clinic for patients due for colonoscopy, we have shown a significant reduction in the nonattendance rate. If all patients were to attend for preassessment, nonattendance rates for colonoscopy might be reduced to that seen in our preassessment group (3.1%).

High prevalence of NSAID enteropathy as shown by a simple faecal test.

BACKGROUND: The diagnosis of non-steroidal anti-inflammatory drug (NSAID) induced enteropathy is difficult, requiring enteroscopy or the use of four day faecal excretion of (111)In labelled white cells. AIMS: To assess faecal calprotectin (a non-degraded neutrophil cytosolic protein) as a method for diagnosing NSAID enteropathy. METHODS: Single stool faecal calprotectin concentrations were compared with the four day faecal excretion of (111)In labelled white cells in 47 patients taking NSAIDs. The prevalence and severity of NSAID enteropathy was assessed using this method in 312 patients (192 with rheumatoid arthritis, 65 with osteoarthritis, 55 with other conditions) taking 18 different NSAIDs. RESULTS: The four day faecal excretion of (111)In white cells correlated significantly with faecal calprotectin concentrations. In the group of 312 patients on NSAIDs faecal calprotectin concentrations were significantly higher than in controls, the prevalence of NSAID enteropathy being 44%. The prevalence and severity of NSAID enteropathy was independent of the particular type or dose of NSAID being taken or other patient variables. CONCLUSIONS: Assay of faecal calprotectin provides a simple practical method for diagnosing NSAID enteropathy in man. Forty four per cent of patients receiving these drugs had NSAID induced enteropathy when assessed by this technique; 20% of these had comparable levels of inflammation to that previously reported in patients with inflammatory bowel disease.

Acute auto immune haemolytic anaemia secondary to hepatitis A infection.

Auto immune haemolytic anaemia has been described in association with a variety of hepatotropic viruses, in particular cytomegalovirus, Epstein-Barr virus and hepatitis B. There is a well-recognized association between chronic active hepatitis and auto immune haemolytic anaemia. We present the first reported case of acute hepatitis A which resulted in a fall in haemoglobin concentration from 14.6 to 4.5 g/dl due to an acute haemolytic anaemia with an associated rise in bilirubin from 149 to 960 mumol/l.

Carcinoma of the oesophagus causing paraparesis by direct extension to the spinal cord.

A 75-year-old man presented with dysphagia and subsequent paraparesis. He was treated by oesophageal dilatation and by the placement of an 8.4 cm Atkinson tube. It was shown that an oesophago-subarachnoid fistula, a rare complication of carcinoma of the oesophagus, had developed. This resulted from direct extension of the tumour to the spinal cord and caused paraparesis unrelated to treatment.