Timothy A. Bakken

Phenotypic Variation of Colonic Motor Functions in Chronic Constipation

BACKGROUND & AIMS Colonic motor disturbances in chronic constipation (CC) are heterogeneous and incompletely understood; the relationship between colonic transit and motor activity is unclear. We sought to characterize the phenotypic variability in chronic constipation. METHODS Fasting and postprandial colonic tone and phasic activity and pressure-volume relationships were assessed by a barostat manometric assembly in 35 healthy women and 111 women with CC who had normal colon transit (NTC; n = 25), slow transit (STC; n = 19), and defecatory disorders with normal (DD-normal; n = 34) or slow transit (DD-slow; n = 33). Logistic regression models assessed whether motor parameters could discriminate among these groups. Among CC, phenotypes were characterized by principal components analysis of these measurements. RESULTS Compared with 10th percentile values in healthy subjects, fasting and/or postprandial colonic tone and/or compliance were reduced in 40% with NTC, 47% with STC, 53% with DD-normal, and 42% with DD-slow transit. Compared with healthy subjects, compliance was reduced (P <or= .05) in isolated STC and DD but not in NTC. Four principal components accounted for 85% of the total variation among patients: factors 1 and 2 were predominantly weighted by fasting and postprandial colonic phasic activity and tone, respectively; factor 3 by postprandial high-amplitude propagated contractions; and factor 4 by postprandial tonic response. CONCLUSIONS Fasting and/or postprandial colonic tone are reduced, reflecting motor dysfunctions, even in NTC. Colonic motor assessments allow chronic constipation to be characterized into phenotypes. Further studies are needed to evaluate the relationship among these phenotypes, enteric neuropathology, and response to treatment in CC.

Pilot study of transesophageal endoscopic epicardial coagulation by submucosal endoscopy with the mucosal flap safety valve technique (with videos)

BACKGROUND We previously demonstrated that the thoracic cavity could be safely accessed by submucosal endoscopy with the mucosal flap safety valve (SEMF) technique. OBJECTIVES To evaluate the technical feasibility of transesophageal access to the heart and epicardial ablation. DESIGN One-week survival study with 5 porcine models. SETTINGS Animal laboratory with general anesthesia. INTERVENTIONS High-pressure carbon dioxide injection and balloon dissection created a large submucosal working space for insertion of a cap-fitted endoscope. A myotomy was performed inside the submucosal space. The thoracic cavity was endoscopically accessed through the myotomy site. A pericardial window was created with a needle-knife. A spot coagulation of the epicardium was performed with a heat probe and a hook-knife. The myotomy site was sealed with the overlying mucosal flap, and the mucosal entry site was closed with clips. MAIN OUTCOME MEASUREMENTS An endoscopy and a necropsy were performed to study the esophagus, mediastinum, pericardial space, and cautery locations on the epicardium one week after the procedure. RESULTS Epicardial coagulation was successfully performed within 30 minutes in 4 of the 5 pigs. Follow-up endoscopy demonstrated completely sealed myotomy sites by the overlying mucosal flap. There was no gross contamination or signs of contamination in the thoracic cavity. The pericardial space was normal in appearance. The epicardial coagulation sites were healing, without exudative ulceration. CONCLUSIONS The SEMF technique allowed endoscopic access to the upper mediastinum, the pericardium, and the epicardium via the esophagus, along with a minimal intervention on the epicardium.

Chemically assisted endoscopic mechanical submucosal dissection by using mesna.

BACKGROUND A class of thiol compounds, mesna (sodium-2-mercaptoethanesulfonate), has been used to facilitate tissue dissection in surgical fields. OBJECTIVES To evaluate the technical feasibility and efficacy of chemically assisted endoscopic mechanical submucosal dissection (CAEMSD) by using mesna. DESIGN An in vivo controlled blind trial by using porcine models. SETTINGS Nonsurvival study in an animal laboratory. INTERVENTIONS Six pigs were studied. Mucosal targets of about 2 cm (estimated) for treatment were created with a circle of cauterized spots along the greater curvature of the gastric body and the antrum. A mesna solution or the control hydroxypropyl methylcellulose solution was submucosally injected. The target mucosa was mechanically isolated with balloon dissection and removed by circumferential incision with a hook-knife inserted into the submucosal space. Necropsy and mucosal specimens from both groups were examined by histology. RESULTS En bloc resection of the target was achieved in all 8 attempts of the mesna group and in 7 of 8 attempts of the control group. Use of mesna significantly reduced tissue resistance to the initial balloon-catheter insertion into the submucosa and the technical difficulty of subsequent submucosal balloon dissection by using a subjective grading system (P < .05). There was no difference in histology between both groups. CONCLUSIONS CAEMSD is a unique methodology to facilitate mucosal resection.