Rescue therapy using a rifabutin-based regimen is effective for cure of Helicobacter pylori infection.

OBJECTIVE: To evaluate the efficacy of rescue therapy using rifabutin, amoxicillin and a proton pump inhibitor (PPI) in the eradication of Helicobacter pylori in patients who have failed at least one course of PPI-based triple therapy. METHODS: The present study was a single-centre case series of 16 consecutive patients who had received at least one course of standard eradication therapy. Pretreatment evaluation included endoscopy with biopsies for histology and culture for H pylori infection. Treatment consisted of a one-week regimen containing a PPI twice daily, amoxicillin (A) 1 g twice daily and rifabutin (R) 300 mg once daily (PPI-AR). Post-treatment evaluation consisted of a repeat endoscopy with biopsy for histology and culture, or a validated urea breath test at least four weeks after treatment was completed. Pretreatment antibiotic susceptibility to metronidazole, clarithromycin and A was evaluated using a validated epsilometer test. RESULTS: Of the 16 patients, four had previously received one course of triple therapy, 10 had received two courses and two had received more than two courses. The overall success rate of PPI-AR was 63% (10 of 16). Resistance to A was 0% (0 of 13), metronidazole 77% (10 of 13), clarithromycin 70% (seven of 10), and both metronidazole and clarithromycin 60% (six of 10). There was no correlation between resistance patterns and cure rate. CONCLUSIONS: An R-containing regimen such as PPI-AR is a viable option as rescue therapy for H pylori infection.

Microsatellite instability in esophageal adenocarcinoma.

The frequency of microsatellite instability (MSI), a result of defective mismatch repair during DNA replication, has been reported inconsistently in primary esophageal adenocarcinoma (EADC). Using a panel of 15 markers, the primary aim of this study was to analyze the frequency of MSI in a well-characterized series of 27 primary EADCs, defined according to strict clinicopathologic criteria. Polymerase chain reaction was used to amplify the following microsatellite repeat loci: D2S123, D10S197, D2S119, D11S904, D2S147, D3S1764, D7S1830, D7S1805, D2S434, D9S299, BAT25, BAT26, D5S346, D17S250, and TGF-beta-RII. Tumors were classified as microsatellite-stable (MSS) when no alterations were seen in tumor DNA compared to matched normal tissues, low-level MSI (MSI-L) when 1-5 of 15 markers were altered, and high-level MSI (MSI-H) when more than five markers were altered. Using these stringent criteria, 9/27 (33%) tumors were MSS, 18/27 (67%) tumors were MSI-L, and no tumor was MSI-H. Immunohistochemistry demonstrated cell nuclear expression of DNA mismatch repair proteins (both hMLH1 and hMSH2) in 78% (21/27) of tumors. No associations were seen between MSI and immunohistochemical expression of hMLH1, hMSH2, alterations in p53 or MBD4, tumor grade, pathologic stage, or patient survival. In conclusion, the finding of low levels of MSI in most tumors suggests an inherent baseline genomic instability, and potentially increased susceptibility to mutations during the progression of esophageal adenocarcinoma.

A survey of Canadian gastroenterologists about the management of Barrett's esophagus.

The aims of the present study were to determine practice patterns of Canadian gastroenterologists for screening patients with Barrett's esophagus and to compare current practice patterns with published guidelines. A secondary goal was to evaluate whether gastroenterologists recommend a "once in a lifetime" endoscopy for patients with chronic gastroesophageal reflux disease. A structured questionnaire regarding screening for Barrett's esophagus was sent to members of the Canadian Association of Gastroenterology. The overall response rate was 51% (203 of 396). Of the 203 respondents, 165 (81%) performed endoscopies in adults and form the basis of this report. The majority of Canadian gastroenterologists followed published guidelines, with 62% screening patients without dysplasia every two years. Patients with low grade dysplasia were screened more frequently, with 54% of respondents performing endoscopy every six months, and 35% on a yearly basis. Biopsy protocols showed the greatest variation, with 46% of gastroenterologists taking four-quadrant biopsies at 2 cm intervals along the columnar-lined (Barrett's) esophagus. Seventy-six per cent of gastroenterologists agreed that all patients with chronic gastroesophageal reflux should have a "once in a lifetime" endoscopy to screen for Barrett's esophagus. The majority of Canadian gastroenterologists follow current guidelines for the management of Barrett's esophagus and support the concept of "once in a lifetime" endoscopy.

ING1 and p53 tumor suppressor gene alterations in adenocarcinomas of the esophagogastric junction.

The aim of this study was to characterize molecular alterations of the recently reported candidate tumor suppressor gene, ING1, and to explore the relationship between ING1 and p53 in a well-defined series of adenocarcinomas of the esophagogastric junction (AdEGJ). Polymerase chain reaction (PCR)-based assays were used to characterize ING1 and p53 alterations, relative to histologically normal esophageal mucosa. Two tumors were found to have ING1 mutations: one novel missense mutation (AGC(Ser)-->ATC(Ile)) at codon 147, and one silent mutation (TCG(Ser)-->TCA(Ser)) at codon 173. Reduced expression of the two major alternatively spliced ING1 messenger RNA variants, p47(ING1a) and p33(ING1b) was variable, but was reduced (1.2-10-fold) in 12 of 19 AdEGJs compared to normal esophageal epithelium. No association between p53 and ING1 alterations was apparent. We conclude that reduced ING1 expression is frequently associated with AdEGJ tumorigenesis, further supporting its role as a tumor suppressor gene, and that ING1 expression is independent of p53 status.

Causation: Recurrent collagenous colitis following repeated use of NSAIDs.

A case in which a patient who on two occasions developed watery diarrhea and proven collagenous colitis shortly after taking nonsteroidal anti-inflammatory drugs is described. The case report suggests a causal relationship.