Genome-wide association study for Crohn's disease in the Quebec Founder Population identifies multiple validated disease loci.

Genome-wide association (GWA) studies offer a powerful unbiased method for the identification of multiple susceptibility genes for complex diseases. Here we report the results of a GWA study for Crohn's disease (CD) using family trios from the Quebec Founder Population (QFP). Haplotype-based association analyses identified multiple regions associated with the disease that met the criteria for genome-wide significance, with many containing a gene whose function appears relevant to CD. A proportion of these were replicated in two independent German Caucasian samples, including the established CD loci NOD2 and IBD5. The recently described IL23R locus was also identified and replicated. For this region, multiple individuals with all major haplotypes in the QFP were sequenced and extensive fine mapping performed to identify risk and protective alleles. Several additional loci, including a region on 3p21 containing several plausible candidate genes, a region near JAKMIP1 on 4p16.1, and two larger regions on chromosome 17 were replicated. Together with previously published loci, the spectrum of CD genes identified to date involves biochemical networks that affect epithelial defense mechanisms, innate and adaptive immune response, and the repair or remodeling of tissue.

Esophageal-left atrial fistula: intraoperative diagnosis and management.

Nontraumatic esophageal-atrial fistulas are usually fatal and are diagnosed postmortem. We report a rare case of intraoperative diagnosis and successful surgical management of an esophageal-left atrial fistula in a 70-year-old woman with a history of brachytherapy, radiotherapy, and chemotherapy for esophageal cancer who presented with progressive dysphagia and hematemesis.

The safety and usefulness of high-dose-rate endoluminal brachytherapy as a boost in the treatment of patients with esophageal cancer with external beam radiation with or without chemotherapy.

PURPOSE: This study reports the results of a single-institution experience with high-dose-rate brachytherapy (HDRBT) used as a boost in the treatment of esophageal cancer with external beam radiation therapy (ERT) with or without chemotherapy. METHODS AND MATERIALS: Patients without evidence of metastatic disease were identified. HDRBT was given before ERT with a dose of 20 Gy in 5 fractions. Patients with a Karnofsky performance of more than 70 received treatment with 50 Gy in 25 fractions and concurrent 5-fluorouracil and cis-platinum during Weeks 1 and 5, whereas patients with a Karnofsky performance of less than 70 were treated with radiation therapy alone with 35 Gy in 14 fractions. RESULTS: Fifty-three patients received HDRBT treatment with combined ERT and chemotherapy and 17 patients with ERT alone. The incidence of acute bone marrow toxicity was 55% Grade 2 and 15% Grade 3, and 85% of patients had Grade 2 esophagitis. With a median follow-up time of 26 months, the median survival was 21 months; the 2-year local recurrence was 25%, and the 5-year survival rate was 28%. CONCLUSION: HDRBT is safe and beneficial for local control in the radical treatment of patients with esophageal cancer.

The role of ciprofloxacin in prolonging polyethylene biliary stent patency: a multicenter, double-blinded effectiveness study.

Plastic stents are the mainstay of the palliation of malignant jaundice but are complicated by recurrent obstruction. Previous trials have failed to demonstrate any improvement in patency with the use of antibiotics. Patients with malignant jaundice were randomized in a double-blind fashion, after polyethylene stent insertion, to receive ciprofloxacin or placebo. After successful stent decompression, there were 50 patients in the treatment arm and 44 in the placebo. There were 14 (33%) episodes of stent occlusion in the ciprofloxacin group versus 23 (49%) in placebo (chi(2) test, P=0.115). There was no significant difference in patency (log-rank test, P=0.17). There were significantly fewer episodes of cholangitis with ciprofloxacin: 10 (23%) versus 21 (42%) in the placebo (P=0.047). The ciprofloxacin group also demonstrated a significant improvement in the Social Function domain of the SF-36 Quality of Life Survey at 1 month (paired T test, P=0.03). The other domains of the SF-36 were not different, nor was survival (log rank, P=0.80). There is insufficient evidence to show that prophylactic ciprofloxacin can prolong plastic biliary stent patency. The observed trends suggest that ciprofloxacin significantly decreases the incidence of cholangitis and results in improvements in certain aspects of quality of life.

Psychosocial correlates of patient-physician discordance in inflammatory bowel disease.

OBJECTIVE: The aim of this study was to identify the independent psychosocial correlates of patient-physician discordance in adult outpatients with inflammatory bowel disease. METHODS: This cross-sectional study was conducted in three university-affiliated tertiary care settings. Psychological distress, social support, perceived stress, and negative life events were assessed, as were demographic, lifestyle, and clinical characteristics. Patient-physician discordance was assessed with 10-item questionnaires. RESULTS: Ten gastroenterologists and 200 of their patients participated. Patients and their physicians disagreed most on discussion of personal issues. Patients with Crohn's disease had statistically significantly higher discordance on disease activity and physical limitation, as well as higher average overall discordance scores than patients with ulcerative colitis. Mean discordance levels were similar across different physicians. Higher psychological distress and more perceived stress were independently associated with higher discordance after controlling for Crohn's disease, active disease, being with the treating physician for less than 1 yr, and recommendation for further medical investigation. Psychological distress was the most important correlate of overall discordance. CONCLUSIONS: Increased physician awareness that psychologically distressed patients have difficulty processing of clinically relevant information may lead to improved doctor-patient communication during an office visit.