OBJECTIVES Dysphagia may develop following antireflux surgery as a consequence of poor esophageal peristaltic reserve. We hypothesized that suboptimal contraction response following multiple rapid swallows (MRS) could be associated with chronic transit symptoms following antireflux surgery. METHODS Wet swallow and MRS responses on esophageal high-resolution manometry (HRM) were characterized collectively in the esophageal body (distal contractile integral (DCI)), and individually in each smooth muscle contraction segment (S2 and S3 amplitudes) in 63 patients undergoing antireflux surgery and in 18 healthy controls. Dysphagia was assessed using symptom questionnaires. The MRS/wet swallow ratios were calculated for S2 and S3 peak amplitudes and DCI. MRS responses were compared in patients with and without late postoperative dysphagia following antireflux surgery. RESULTS Augmentation of smooth muscle contraction (MRS/wet swallow ratios > 1.0) as measured collectively by DCI was seen in only 11.1% with late postoperative dysphagia, compared with 63.6% in those with no dysphagia and 78.1% in controls (P≤0.02 for each comparison). Similar results were seen with S3 but not S2 peak amplitude ratios. Receiver operating characteristics identified a DCI MRS/wet swallow ratio threshold of 0.85 in segregating patients with late postoperative dysphagia from those with no postoperative dysphagia with a sensitivity of 0.67 and specificity of 0.64. CONCLUSIONS Lack of augmentation of smooth muscle contraction following MRS is associated with late postoperative dysphagia following antireflux surgery, suggesting that MRS responses could assess esophageal smooth muscle peristaltic reserve. Further research is warranted to determine if antireflux surgery needs to be tailored to the MRS response.

The inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the intestine. The prevalence in the United States is greater than 200 cases per 100,000, with the total number of IBD patients between 1 and 1.5 million. CD may affect all parts of the gastrointestinal tract, from mouth to anus, but most commonly involves the distal part of the small intestine or ileum, and colon. UC results in colonic inflammation that can affect the rectum only, or can progress proximally to involve part of or the entire colon. Clinical symptoms include diarrhea, abdominal pain, gastrointestinal bleeding, and weight loss. A serious long-term complication of chronic inflammation is the development of colorectal cancer. A genetic basis for IBD had long been recognized based on the increased familial risk. However, significant discordance for CD in twins, and a much less robust phenotypic concordance for UC, suggested additional factors play a role in disease pathogenesis, including environmental factors. In the past several years, progress in understanding the molecular basis of IBD has accelerated, beginning with the generation of animal models of colitis and progressing to the identification of specific genetic markers from candidate gene, gene linkage, and genome-wide association analyses. Genetic studies have also resulted in the recognition of the importance of environmental factors, particularly the crucial role of the gut microbiota in CD and UC. Altered immune responses to the normal intestinal flora are key factors in IBD pathogenesis. In this research topic, the genetic basis of IBD, the genetic and cellular alterations associated with colitis-associated colon cancer, and the emerging role of the intestinal microbiota and other environmental factors will be reviewed.

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Background When multiple swallows are rapidly administered, esophageal peristalsis is inhibited, and pronounced lower esophageal sphincter relaxation ensues. After the last swallow of the series, a robust contraction sequence results. The authors hypothesize that multiple rapid swallows (MRS) may have value in predicting esophageal transit symptoms in patients undergoing laparoscopic antireflux surgery (LARS). Methods Records of patients undergoing esophageal high-resolution manometry (HRM) before LARS were evaluated. The evaluation of MRS included adequate inhibitory response during swallows and the contraction pattern after MRS. Dysphagia was scored based on a product of symptom frequency and severity using 5-point Likert scales. A composite dysphagia score comprised the sum of scores for solid and liquid dysphagia, and a score of 4 or higher was considered clinically significant. The normal and abnormal MRS responses of patients with preoperative, early, and late postoperative dysphagia were compared with those of patients with no dysphagia. Results In this study, 63 patients (mean age, 60.3 ± 1.7 years, 48 women) undergoing HRM before LARS successfully performed MRS (median, 5 swallows; longest interval between swallows, 3.2 ± 0.1 s). After MRS, 14 patients (22.2 %) had an intact peristaltic sequence. Complete failure of peristalsis was seen in 21 (33.3 %), and incomplete esophageal inhibition in 25 (39.7 %) of the remaining patients. When stratified by presence or absence of dysphagia, 58.3 % of the subjects without dysphagia had a normal MRS response, whereas 83.3 % had formation of peristaltic segments after MRS. In contrast, only 14 % of the subjects with dysphagia had a normal MRS response (p ≤ 0.003 vs. the subjects with no dysphagia). Abnormal MRS responses were more prevalent in the patients with any preoperative and late postoperative dysphagia (p = 0.04 across groups) and in those with clinically significant dysphagia (p = 0.08 across groups). Conclusions High-resolution manometry with MRS helps to predict dysphagia in subjects undergoing preoperative esophageal function testing before LARS.

The intestinal epithelium contains a rapidly proliferating and perpetually differentiating epithelium. The principal functional unit of the small intestine is the crypt-villus axis. Stem cells located in the crypts of Lieberkühn give rise to proliferating progenitor or transit amplifying cells that differentiate into the four major epithelial cell types. The study of adult gastrointestinal tract stem cells has progressed rapidly with the recent discovery of a number of putative stem cell markers. Substantial evidence suggests that there are two populations of stem cells: long-term quiescent (reserved) and actively cycling (primed) stem cells. These are in adjoining locations and are presumably maintained by the secretion of specific proteins generated in a unique microenvironment or stem cell niche surrounding each population. The relationship between these two populations, and the cellular sources and composition of the surrounding environment remains to be defined, and is an active area of research. In this review we will outline progress in identifying stem cells and defining epithelial-mesenchymal interactions in the crypt. We will summarize early advances using stem cells for therapy of gastrointestinal disorders.