Phenotypic diversity in patients with multiple serrated polyps: a genetics clinic study.

OBJECTIVE: Hyperplastic polyposis is a colonic polyposis condition of unknown aetiology. The purpose of this study was to examine the spectrum of phenotypic variation in patients with multiple serrated polyps as a basis for gene discovery. METHODS: One hundred and twenty-six patients with multiple (> or = 5) serrated polyps were recruited to the study. Polyp counts were extracted from histology and colonoscopy reports. Ethnicity was self-reported. Family history of cancer data were derived from pedigrees. Ascertainment status was classified as either index case or identified by screening. RESULTS: The average reported polyp count was 39. Patients with highest polyp numbers were more likely to be male (P = 0.02). Colorectal cancer (CRC) was identified in 49 of 119 patients (41%) and 28% of these patients had multiple CRC. Young onset patients had higher polyp numbers (P = 0.03) and were more likely to have their CRC in the distal colon (P = 0.02). CRC was significantly associated with the presence of adenomas (P = 0.03). Patients were divided into moderate polyposis (5-79 serrated polyps) and dense polyposis (80 or more) categories. The dense polyposis category was associated with a lack of family history for CRC (P = 0.034) and male gender (P = 0.014), independent of ascertainment status and recruitment site. CONCLUSION: Multiple serrated polyps were associated with an increased personal risk of CRC. A subset of patients with the highest polyp numbers was more likely to be male and to have no family history of CRC. This result suggests heterogeneous modes of inheritance and has implications for studies investigating the genetic basis of multiple serrated polyps.

Effects of age on the gastroesophageal junction, esophageal motility, and reflux disease.

BACKGROUND & AIMS: The prevalence of complicated gastroesophageal reflux disease (GERD) increases with age; however, the mechanism by which this occurs is uncertain. This study assessed (1) whether physiologic degradation of the gastroesophageal junction and esophageal motility occurs with aging, and (2) whether these effects are associated with increased esophageal acid exposure and reflux symptoms in the elderly. METHODS: Retrospective study of 1307 patients referred for investigations of reflux symptoms (median age, 49 years; range, 15-92 years) was conducted. Manometry assessed LES pressure, LES length, and esophageal peristalsis. Ambulatory pH studies assessed esophageal acid exposure (% time pH <4) during a period of 24 hours; reflux symptoms were assessed by validated questionnaire. RESULTS: On multivariate regression, esophageal acid exposure was associated independently with decreasing LES pressure (P < .0001) and abdominal LES length (P < .0004). Dysmotility exacerbated reflux in the recumbent position (P < .004). Acid exposure increased with age (P < .0001), a 1.1%/24 hours (95% confidence interval, 0.4%-1.4%) increase in acid exposure every decade (more pronounced in the recumbent position). The age-related increase in acid exposure was associated independently with decreasing abdominal LES length (P < .001) and increasing dysmotility (P < 0.01). Reflux symptoms increased with acid exposure (P < .001); however, at any given level of exposure, symptom severity was less in the elderly (P < .006). CONCLUSIONS: Age was associated with an increase in esophageal acid exposure; however, the severity of reflux symptoms reduced with age. These changes were associated with progressive decrease in abdominal LES length and esophageal motility. Increasing GERD severity in the elderly is related to degradation of the gastroesophageal junction and impaired esophageal clearance.