A pleiotropy scan to discover new susceptibility loci for pancreatic ductal adenocarcinoma.

Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted ten years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61,052 variants reported to be associated by at least one genome wide association study (GWAS) with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16,055 pancreatic ductal adenocarcinoma (PDAC) cases and 212,149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P=6.52×10-5) and 7q36.3-rs288762 (P=3.03×10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.

Laparoscopic Gastric Greater Curvature Plication: Intermediate Results and Factors Associated with Failure.

BACKGROUND: Laparoscopic gastric greater curvature plication (LGGCP) is a novel bariatric procedure. Few studies have presented intermediate or long-term results. The aim of this prospective study was to investigate intermediate results and factors associated with failure to achieve satisfactory weight loss after LGGCP. METHODS: Between October 2011 and November 2013, 61 patients underwent LGGCP and were followed up to 36 months after operation. Demographics, comorbidities, complications, and percentage of excess body mass index loss (%EBMIL) were analyzed. Logistic regression analysis was used to determine independent risk factors for weight loss failure 3 years after LGGCP. RESULTS: Forty-eight women and 13 men with an average age of 47.7 ± 10.3 years and preoperative BMI of 46.3 ± 5.8 underwent LGGCP. Postoperative complications were observed in three patients (4.9%) and two of them (3.3%) underwent reoperations. Follow-up rate was 95%, 91.7, and 88.3% after 1, 2, and 3 years, respectively. Average %EBMIL after 1 year was 47.25 ± 21.6, 44.8 ± 25.9 after 2 years, and 41.9 ± 25.6 after 3 years. Gastroscopy 3 years after LGGCP demonstrated intact plication fold in 55% of cases. Preoperatively, GERD was present in 46% of patients. Prevalence of GERD 3 years after LGGCP was 34.6%. Remission rates of type 2 diabetes mellitus and hypertension were 27.8 and 38.3%, respectively. Higher postoperative hunger sensation was found to be an independent factor (OR 1.6, 95% 1.141-2.243; p = 0.002) associated with unsatisfactory weight loss after LGGCP. CONCLUSIONS: Patients with LGGCP had postoperative complication rate 4.9% and achieved only modest weight loss after 3 years. Increased hunger was an independent risk factor associated with unsatisfactory weight loss after LGGCP. Long-term follow-up data are needed to define the role of LGGCP in the treatment of morbid obesity.

Predictors of response to short-term proton pump inhibitor treatment in laryngopharyngeal reflux patients.

OBJECTIVES: To assess benefit from one and three months' empirical proton pump inhibitor treatment in patients with suspected laryngopharyngeal reflux, and to define pre-therapy factors which may predict success with short-term proton pump inhibitor treatment. STUDY DESIGN: Prospective, open clinical study. MATERIALS AND METHODS: One hundred adult out-patients with suspected laryngopharyngeal reflux were enrolled in the study. Laryngopharyngeal reflux patients underwent endoscopy and received omeprazole for three months. Efficacy of treatment was assessed at one and three months. Patients were classified as responders if their total symptom score had improved at least 50 per cent, their videolaryngoscopic score had improved by at least two points, and they were satisfied with the results. Pre-therapy factors assessed for an effect on omeprazole outcomes included: patient demographics, reflux symptoms, videolaryngoscopic scores, endoscopic findings, overall vocal dysfunction degree, self-rated voice handicap index, hospital anxiety and depression scale scores, and general well-being score. RESULTS: Fifty-six per cent of patients were classified as responders at one month of treatment; this proportion rose to 92 per cent at three months. Those patients entering the study with a higher heartburn score showed a significant response after one month of omeprazole treatment. Non-responders were found to have significantly more anxiety than responders. Logistic regression analysis revealed these factors, plus the medication dose, as being relevant for faster response prediction. No significant association was found between pre-therapy factors and three-month response to proton pump inhibitor treatment. CONCLUSION: Three months of proton pump inhibitor treatment twice daily is warranted for confirming suspicion of laryngopharyngeal reflux. Baseline anxiety levels and heartburn scores, and the medication dose, may be relevant factors when predicting faster response to proton pump inhibitor treatment in carefully selected patients.

Clinical trial: randomized-controlled clinical study comparing the efficacy and safety of a low-volume vs. a high-volume mesalazine foam in active distal ulcerative colitis.

BACKGROUND: Rectally administered mesalazine (mesalamine; 5-aminosalicylic acid) is the first-line therapy for treatment of distal ulcerative colitis. Recently, a high-volume 5-aminosalicylic acid foam has been shown to be as effective and safe as standard 5-aminosalicylic acid enema. AIM: To study the efficacy and safety of a low-volume vs. a high-volume 5-aminosalicylic acid foam. METHODS: In this investigator-blinded study, patients with active distal ulcerative colitis [Clinical Activity Index (CAI) > 4, Endoscopic Index > or = 4] were randomized to receive 2 x 1 g/30 mL low-volume (n = 163) or 2 x 1 g/60 mL high-volume 5-aminosalicylic acid foam (n = 167) for 42 days. Primary end point was clinical remission (CAI < or = 4) at the final/withdrawal visit (per-protocol). RESULTS: 330 patients were evaluable for efficacy and safety by intention-to-treat, 290 for per-protocol analysis. Clinical remission rates at week 6 (per-protocol) were 77% on low-volume foam vs. 77% on high-volume foam (P = 0.00002 for non-inferiority). The low-volume foam was associated with a lower frequency of severe discomfort, pain and retention problems. CONCLUSIONS: Low-volume 5-aminosalicylic acid foam is as effective and safe as a high-volume 5-aminosalicylic acid foam in the treatment of active distal ulcerative colitis, but offers compliance advantages compared to the high-volume preparation.

Use of sedation for routine diagnostic upper gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy Survey of National Endoscopy Society Members.

BACKGROUND/AIMS: Sedation rates may vary among countries, depending on patients' and endoscopists' preferences. The aim of this survey was to investigate the rate of using premedication for routine diagnostic upper gastrointestinal (UGI) endoscopy in endoscopy societies, members of the European Society of Gastrointestinal Endoscopy (ESGE). METHODS: We evaluated a multiple-choice questionnaire which was e-mailed to representatives of national endoscopy societies, which are members of the ESGE. The questionnaire had 14 items referring to endoscopy practices in each country and the representatives' endoscopy units. RESULTS: The response rate was 76% (34/45). In 47% of the countries, less than 25% of patients undergo routine diagnostic UGI endoscopy with conscious sedation. In 62% of the responders' endoscopy units, patients are not asked their preference for sedation and do not sign a consent form (59%). Common sedatives in use are midazolam (82%), diazepam (38%) or propofol (47%). Monitoring equipment is not available 'in most of the endoscopy units' in 46% (13/28) of the countries. Though they were available in 91% of the national representatives' endoscopy units, they are rarely (21%) used to monitor unsedated routine diagnostic UGI endoscopy. CONCLUSIONS: In about 50% of ESGE-related countries, less than 25% of patients are sedated for routine diagnostic UGI endoscopy. Major issues to improve include availability of monitoring equipment and the use of a consent form.