Impact on sleeve gastrectomy in patients with esophageal motor disorder.

BACKGROUND: Gastroesophageal reflux disease (GERD) and esophageal motor disorders (EMD) are frequent conditions among patients with obesity. The effects of sleeve gastrectomy (SG) on esophageal function can worsen GERD, but little is known about its effects on EMD and the consequences of preexisting EMD on GERD after SG. OBJECTIVES: To study the postoperative outcomes of SG in a population of patients displaying preexisting EMD. SETTING: University Hospital, France. METHODS: Patients with EMD confirmed by high-resolution manometry who underwent a laparoscopic SG between 2010 and 2019 were retrospectively included in this monocenter study. GERD symptoms and high-resolution manometry results were recorded before surgery and during follow-up. Conversion to gastric bypass were also recorded. RESULTS: Thirty-seven patients were included. Mean age was 52.6 ± 12.9 years. Most patients were female (70%). EMD were achalasia (19% of patients), hypercontractile (22%), hypocontractile (30%) and nutcracker esophagus (22%), and ineffective esophageal motility (8%). GERD symptoms were present in 10 patients (27%) preoperatively and 18 (49%) postoperatively. Achalasia was not resolved after SG and was constantly associated with disabling food blockage or GERD symptoms after surgery, and 3 of 4 patients with nutcracker esophagus had postoperative GERD symptoms and underwent gastric bypass. CONCLUSIONS: This study is the largest to describe the course of GERD and EMD after SG in patients displaying preoperative EMD. Achalasia and nutcracker esophagus are associated with poorer postoperative outcomes, and another procedure such as a gastric bypass should be performed.

IL-7 receptor influences anti-TNF responsiveness and T cell gut homing in inflammatory bowel disease.

It remains unknown what causes inflammatory bowel disease (IBD), including signaling networks perpetuating chronic gastrointestinal inflammation in Crohn's disease (CD) and ulcerative colitis (UC), in humans. According to an analysis of up to 500 patients with IBD and 100 controls, we report that key transcripts of the IL-7 receptor (IL-7R) pathway are accumulated in inflamed colon tissues of severe CD and UC patients not responding to either immunosuppressive/corticosteroid, anti-TNF, or anti-α4ß7 therapies. High expression of both IL7R and IL-7R signaling signature in the colon before treatment is strongly associated with nonresponsiveness to anti-TNF therapy. While in mice IL-7 is known to play a role in systemic inflammation, we found that in humans IL-7 also controlled α4ß7 integrin expression and imprinted gut-homing specificity on T cells. IL-7R blockade reduced human T cell homing to the gut and colonic inflammation in vivo in humanized mouse models, and altered effector T cells in colon explants from UC patients grown ex vivo. Our findings show that failure of current treatments for CD and UC is strongly associated with an overexpressed IL-7R signaling pathway and point to IL-7R as a relevant therapeutic target and potential biomarker to fill an unmet need in clinical IBD detection and treatment.