Impact of Objective Colonic and Whole Gut Motility Data as Measured by Wireless Motility Capsule on Outcomes of Antireflux Surgery.

BACKGROUND: Studies show higher rates of dissatisfaction with antireflux surgery (ARS) outcomes in patients with chronic constipation. This suggests a relationship between colonic dysmotility and suboptimal surgical outcome. However, due to limitations in technology, there is no objective data available examining this relationship. The wireless motility capsule (WMC) is a novel technology consisting of an ingestible capsule equipped with pH, temperature, and pressure sensors, which provide information regarding regional and whole gut transit times, pH and motility. The aim of this study was to assess the impact of objective regional and whole gut motility data on the outcomes of ARS. STUDY DESIGN: This was a retrospective review of patients who underwent WMC testing before ARS. Transit times, motility, and pH data obtained from different gastrointestinal tract regions were used in analysis to determine factors that impact surgical outcome. A favorable outcome was defined as complete resolution of the predominant reflux symptom and freedom from antisecretory medications. RESULTS: The final study population consisted of 48 patients (fundoplication [n = 29] and magnetic sphincter augmentation [n = 19]). Of those patients, 87.5% were females and the mean age ± SD was 51.8 ± 14.5 years. At follow-up (mean ± SD, 16.8 ± 13.2 months), 87.5% of all patients achieved favorable outcomes. Patients with unfavorable outcomes had longer mean whole gut transit times (92.0 hours vs 55.7 hours; p = 0.024) and colonic transit times (78.6 hours vs 47.3 hours; p = 0.028), higher mean peak colonic pH (8.8 vs 8.15; p = 0.009), and higher mean antral motility indexes (310 vs 90.1; p = 0.050). CONCLUSIONS: This is the first study to demonstrate that objective colonic dysmotility leads to suboptimal outcomes after ARS. WMC testing can assist with preoperative risk assessment and counseling for patients seeking ARS.

Affinity regulates spatial range of EGF receptor autocrine ligand binding.

Proper spatial localization of EGFR signaling activated by autocrine ligands represents a critical factor in embryonic development as well as tissue organization and function, and ligand/receptor binding affinity is among the molecular and cellular properties suggested to play a role in governing this localization. We employ a computational model to predict how receptor-binding affinity affects local capture of autocrine ligand vis-a-vis escape to distal regions, and provide experimental test by constructing cell lines expressing EGFR along with either wild-type EGF or a low-affinity mutant, EGF(L47M). The model predicts local capture of a lower affinity autocrine ligand to be less efficient when the ligand production rate is small relative to receptor appearance rate. Our experimental data confirm this prediction, demonstrating that cells can use ligand/receptor binding affinity to regulate ligand spatial distribution when autocrine ligand production is limiting for receptor signaling.