Sepsis and elevated liver enzymes in a patient with inflammatory bowel disease: think of portal vein thrombosis.

A 42-year old man, 1 year previously diagnosed with ulcerative colitis after an emergency subtotal colectomy with formation of an ileostomy because of severe colitis with perforation, was admitted with sepsis and jaundice. The liver enzymes were elevated and blood cultures were positive for Streptococcus milleri. Magnetic resonance imaging showed a complete thrombosis of the main stem of the portal vein with occlusion of the left branch. Intravenous antibiotic therapy combined with heparinisation led to complete recanalisation of the thrombus. Portal vein thrombosis is a rare complication of inflammatory bowel disease and has been described in only 10 patients thus far. Multiple aetiologic factors may be responsible in relation to inflammatory bowel disease, such as hypercoagulability, thrombocytosis and abdominal sepsis. In patients with inflammatory bowel disease, unexplained sepsis and abnormal liver function tests, the possibility of an acute portal vein thrombosis should be considered and investigated, because unrecognised it may have serious long-term complications.

Genome wide array comparative genomic hybridisation analysis of premalignant lesions of the stomach.

BACKGROUND: Gastric cancer is one of the most frequent malignancies in the world, ranking fifth in the Netherlands as a cause of cancer death. Surgery is the only curative treatment for advanced cases, but results of gastrectomy largely depend on the stage of the disease. A better understanding of the mechanisms of progression from a preneoplastic condition through intraepithelial neoplasia to invasive cancer may provide information relevant to designing focused prevention strategies. METHODS: Because the pattern of chromosomal aberrations in precursors of gastric cancer is unclear, 11 gastric polyps with intraepithelial neoplasia (three hyperplastic polyps and eight adenomas) were analysed by microarray comparative genomic hybridisation to study chromosomal instability in precursors of gastric cancer. RESULTS: Chromosomal aberrations were detected in all specimens. Adenomas showed no more chromosomal aberrations than did the hyperplastic polyps. The most frequent aberrations were gain of 7q36 and 20q12, and loss of 5q14-q21 in the adenomas, and loss of 15q11-14, 1p21-31, and 21q11-21.2 in the hyperplastic polyps. The most frequent chromosomal aberration in common to both types was loss of 9p21.3. CONCLUSION: Hyperplastic polyps showed many chromosomal aberrations, confirming that neoplastic transformation can occur in these lesions. These observations are consistent with the existence of two morphologically and genetically distinct pathways to gastric cancer-the hyperplastic polyp pathway and the (intestinal type) adenoma pathway. The relative contribution of each to gastric carcinogenesis in general, and how they compare to patterns of chromosomal aberrations in the more prevalent flat foci of intraepithelial neoplasia remain to be determined.

Comparative genomic hybridisation as a supportive tool in diagnostic pathology.

AIMS: Patients with multiple tumour localisations pose a particular problem to the pathologist when the traditional combination of clinical data, morphology, and immunohistochemistry does not provide conclusive evidence to differentiate between metastasis or second primary, or does not identify the primary location in cases of metastases and two primary tumours. Because this is crucial to decide on further treatment, molecular techniques are increasingly being used as ancillary tools. METHODS: The value of comparative genomic hybridisation (CGH) to differentiate between metastasis and second primary, or to identify the primary location in cases of metastases and two primary tumours was studied in seven patients. CGH is a cytogenetic technique that allows the analysis of genome wide amplifications, gains, and losses (deletions) in a tumour within a single experiment. The patterns of these chromosomal aberrations at the different tumour localisations were compared. RESULTS: In all seven cases, CGH patterns of gains and losses supported the differentiation between metastasis and second primary, or the identification of the primary location in cases of metastases and two primary tumours. CONCLUSION: The results illustrate the diagnostic value of CGH in patients with multiple tumours.

Increased apoptosis in gastric mucosa adjacent to intestinal metaplasia.

BACKGROUND: The biological processes involved in the development of gastric mucosal atrophy and intestinal metaplasia are still incompletely understood. Reports testing the hypothesis that apoptosis leads to atrophy have yielded conflicting results. The availability of new antibodies for the detection of apoptotic cells in tissue sections has facilitated the analysis of the role of apoptosis in the gastritis-atrophy-intestinal metaplasia sequence. METHODS: Archival material from 40 gastric resection specimens with normal mucosa (n = 5), chronic active gastritis (n = 17), or intestinal metaplasia (n = 18) was studied. Immunohistochemistry was performed using antibodies directed against cleaved cytokeratin 18 and active caspase 3. Slides were scored on a 0-3 scale for the presence of apoptotic cells. RESULTS: Normal gastric mucosa contained low numbers of apoptotic cells at the surface epithelium (mean score, 0.20). This number was significantly increased in cases with chronic gastritis (mean score, 1.06) and in those with intestinal metaplasia (mean score, 2.56). Within the intestinal metaplasia cases, 44 different foci of intestinal metaplasia were identified. In 39 of these 44 areas, concentrations of apoptotic cells were seen immediately adjacent to the foci of intestinal metaplasia, but not in the metaplastic epithelium itself. CONCLUSIONS: Apoptosis is uncommon in normal gastric mucosa. Chronic inflammation and intestinal metaplasia are associated with increased apoptosis, but occur mainly at the mucosal surface and not in the deeper layers. These findings do not support the concept that apoptosis underlies the loss of gastric glands and leads to atrophy, but the observed concentration of apoptotic epithelial cells adjacent to foci of intestinal metaplasia could be related to heterogeneity of epithelial damage, causing apoptosis, to which intestinal metaplasia is a response.

Surveillance in Barrett's oesophagus: a critical reappraisal.

BACKGROUND: Current recommendations are for endoscopic surveillance of patients with Barrett's oesophagus to detect dysplasia and to diagnose carcinoma at an early and possibly treatable stage. However, observations suggest that these current practice guidelines are thwarted by many factors often not taken into account. These observations stem from general surveillance aspects as well from specific data on Barrett's oesophagus. This review therefore aims at discussing data on the current surveillance strategy in conjunction with general surveillance aspects relevant for their interpretation. METHODS: Literature survey of published articles. RESULTS: A critical reappraisal of the literature shows that the current surveillance strategy is hampered by multiple problems with the marker dysplasia, cost-ineffectiveness, an overrated cancer risk and an astonishing lack of prospective, randomized data showing a clear benefit in terms of a greater life expectancy. Moreover, the decisive study is unlikely ever to be performed because of the large number of patients needed and the required length of follow-up. As a result, protocols are being carried out that have never been critically tested prior to large-scale clinical implementation. CONCLUSIONS: Although these findings should not lead to therapeutic nihilism, the data raise the issue of whether or not surveillance protocols should be restricted to specialized referral centres with particular research efforts aimed at improving existing and developing new techniques that lack most of the described pitfalls and problems. Since it is foreseen that matters will not change rapidly in the (near) future, the clinician has no other choice than to rely on individually tailored arguments to survey taking into account for example family history, age and anxiety about potential long-term effects.

Effects of prucalopride on colonic transit, anorectal function and bowel habits in patients with chronic constipation.

BACKGROUND: There is a need for better tolerated drugs to normalize bowel function in chronic constipation. Prucalopride is a highly selective, specific, serotonin4 receptor agonist with enterokinetic properties. AIM: To evaluate the effects of prucalopride on bowel function, colonic transit and anorectal function in patients with chronic constipation. METHODS: Twenty-eight patients were enrolled in this double-blind, placebo-controlled, crossover study (prucalopride: 1 mg, n=12; 2 mg, n=16). Patients kept a bowel function diary. Colonic transit times and anorectal function (anal manometry, rectal sensitivity and rectal compliance) were assessed. RESULTS: Prucalopride (1 mg) compared to placebo significantly increased the mean number of spontaneous complete, spontaneous and all bowel movements per week. Prucalopride (1 mg) significantly decreased the percentage of bowel movements with hard/lumpy stools and straining and increased the urge to defecate. Prucalopride (1 and 2 mg) decreased the mean total colonic transit time by 12.0 h (prucalopride 42.8 h vs. placebo 54.8 h; P=0.074). No statistically significant effects were found in any of the anorectal function parameters. Prucalopride was well tolerated. There were no clinically relevant changes in standard safety parameters. CONCLUSIONS: Prucalopride significantly improves stool frequency and consistency, and the urge to defecate, and may decrease colonic transit times in patients with chronic constipation.