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Roxana Chis,1 Simon Hew,2 Wilma Hopman,3 Lawrence Hookey,2 Robert Bechara2 1Division of Internal Medicine, Kingston Health Sciences Centre, Queen’s University, Kingston, Ontario, Canada; 2Division of Gastroenterology, Kingston Health Sciences Centre, Queen’s University, Kingston General Hospital, Kingston, Ontario, Canada; 3Research Institute, Kingston Health Sciences Centre, Queen’s University, Kingston, Ontario, CanadaCorrespondence: Robert BecharaDivision of Gastroenterology, Queens University, Kingston Health Sciences Center, 166 Brock Street, Kingston, Ontario K7L1A8, CanadaTel + 613 544 3400Email bechara.robert@gmail.comPurpose: Patients with Barrett’s esophagus (BE) undergo surveillance endoscopies to assess for pre-cancerous changes. We developed a simple endoscopic classification method for predicting non-dysplastic BE (NDBE), low-grade dysplasia (LGD)/indefinite for dysplasia (ID) and high-grade dysplasia (HGD)/early esophageal adenocarcinoma (EAC).Patients and Methods: Twenty-two patients with BE underwent endoscopy using the PENTAX Medical MagniView gastroscope and OPTIVISTA processor. Sixty-six video-still images were analyzed to characterize the microsurface, microvasculature and the presence of a demarcation line. Class A was characterized by regular microvascular and microsurface patterns and absence of a demarcation line, class B by changes in the microvascular and/or microsurface patterns compared to the background mucosa with presence of a demarcation line, and class C by irregular microvascular and/or irregular microsurface patterns with presence of a demarcation line.Results: Of the class A images, 97.9% were NDBE. For class B, 69.2% were LGD/ID and 30.8% NDBE. One hundred percent of the class C samples were HGD/EAC. The sensitivity of our classification system was 93.8%, specificity 92%, positive predictive value 78.9%, negative predictive value 97.9% and an accuracy 92.4%.Conclusion: In this study, we developed a simple classification system for the prediction of NDBE, LGD/ID and HGD/EAC. Its real-time clinical applicability will be validated prospectively.Keywords: Barrett’s esophagus, BE, dysplasia, enhanced endoscopy, esophageal adenocarcinoma

Aim: To investigate the impact of PD-L1 expression status on consolidative durvalumab efficacy and safety in stage III NSCLC patients. Methods: This retrospective, ethics board approved, multi-centre study included all patients with histologically and/or cytologically confirmed unresectable stage III NSCLC, EGFR/ALK wild-type patients who completed concurrent chemoradiation therapy (cCRT) from January 2018 to August 2020 at the Cancer Centre of Southeastern Ontario and The Ottawa Hospital Cancer Centre. PD-L1 status was grouped as ≥50% vs. 1–49% vs.

Background: Gastrin plays an important role in the regulation of gastric acid secretion in humans. Tumour necrosis factor alpha (TNF-α) stimulates gastrin release from antral G cells in vitro. The aim was to determine whether gastrin release decreases in patients with Crohn disease treated with monoclonal antibody to TNF-α. Methods: Twenty-five consecutive patients with Crohn disease (10 M, 15 F; 18 with fistulas) were treated with a single intravenous infusion of the monoclonal antibody to TNF-α, infliximab, at a dose of 5 mg/kg. Basal and bombesin stimulated gastrin was measured after an overnight fast immediately before and 2 weeks after infliximab. Helicobacter pylori status was determined by serology. Results: Twenty-two patients were H. pylori -negative. Basal plasma gastrin was 21 (16-26) pmol/L before and 19 (15-25) pmol/L after infliximab (NS). Bombesin stimulated gastrin decreased from 49 (40-62) pmol/L before to 36 (33-59) pmol/L ( P < 0.005) 2 weeks after infliximab. Conclusion: Gastrin release in response to bombesin decreases in patients with Crohn disease treated with infliximab. [ABSTRACT FROM AUTHOR]

The distal gut hormone peptide YY (PYY) mediates feedback inhibition of gastric acid secretion, gastrointestinal motility, and pancreatic enzyme output. To investigate the influence of maldigestion on PYY, we determined plasma PYY levels in patients with celiac disease under basal conditions and in response to intraduodenal fat. Basal PYY was increased in untreated celiac patients (N = 13) compared to patients on a gluten free diet (N = 9) [15.6 (11.8-27.0) pM vs 12.2 (10.1-13.1) pM; P < 0.05] and compared to control subjects (N = 15) [9.5 (8.3-10.4) pM; P < 0.001]. Integrated PYY in response to intraduodenally infused predigested fat (1071+/-293 pM 80 min) was significantly (P < 0.05) greater than in response to undigested fat (322+/-223 pM 80 min) in six untreated celiacs. Plasma concentrations of PYY and cholecystokinin were strongly correlated (r = 0.79; P < 0.001). We conclude that basal PYY levels in untreated celiac disease are elevated, that predigestion of fat enhances PYY release in these patients, and that PYY secretion is correlated with CCK release. [ABSTRACT FROM AUTHOR]

Background: To further establish its role in the ileal brake mechanism, we determined the effect of the distal gut hormone peptide YY (PYY) on gallbladder motility and plasma gut hormones during the cephalic phase of meal stimulation. Methods: Eight healthy volunteers were studied in a randomized crossover design, with or without intravenous infusion of a physiological dose of PYY. On each occasion, subjects underwent modified sham feeding followed by real feeding. Results: PYY reduced gallbladder emptying in response to modified sham feeding from 23 ± 5% to 5 ± 7% (P < 0.01) and integrated plasma pancreatic polypeptide from 2337 ± 397 pmol/L × 90 min to 903 ± 232 pmol/L × 90 min (P < 0.01). PYY enhanced plasma cholecystokinin in response to real feeding from 53 ± 9 pmol/L × 90 min to 82 ± 17 pmol/L × 90 min (P < 0.05), but did not significantly affect maximum gallbladder emptying and tended to decrease plasma pancreatic polypeptide. Conclusion: Circulating PYY suppresses the cephalic phase of postprandial gallbladder emptying, but not meal stimulated maximum emptying. The results support the hypothesis that the effect of PYY on gallbladder emptying is mediated by vagal-dependent rather than cholecystokinin-dependent pathways. [ABSTRACT FROM AUTHOR]

Background: Intestinal fat inhibits gastric acid secretion and induces release of peptide YY (PYY) into the circulation. The aim of this study was to further establish the role of circulating PYY in the inhibition of gastric acid secretion by intraduodenal fat. Methods: Plasma PYY concentrations and gastrin-stimulated gastric acid output were measured in response to intravenous infusion of PYY in eight healthy men. The results were compared with those obtained after intraduodenal administration of dietary fat. Results: Plasma PYY concentrations increased by 8.1 ± 1.8 pmol/l (P < 0.005) in response to the lower and by 13.5 ± 2.5 pmol/l (P < 0.005) in response to the higher PYY dose. These increments were comparable to those observed after intraduodenal fat (10.3 ± 2.4 pmol/l). Intraduodenal fat significantly inhibited (P < 0.005 versus control) gastrin-stimulated gastric acid secretion by 74% ± 6%, but neither the lower (3% ± 7%; NS) nor the higher PYY dose (1% ± 10%; NS) induced any change in gastric acid output. PYY was biologically active, as reflected by a significant delay (P = 0.04) of orocaecal transit time. Conclusion: Release of PYY into the circulation is not responsible for inhibition of gastrin-stimulated gastric acid secretion by dietary fat. [ABSTRACT FROM AUTHOR]

Background: Peptide YY (PYY) is a gut hormone produced by endocrine cells in the distal small bowel, colon, and rectum. PYY inhibits upper gastrointestinal secretory and motor functions. The aim of this study was to determine whether basal and postprandial plasma PYY levels in patients with proctocolectomy and ileal pouch-anal anastomosis (IPAA) are reduced and to determine the relationship between plasma PYY and plasma cholecystokinin (CCK) levels. Methods: Plasma concentrations of PYY and CCK were measured before and after ingestion of a standardized breakfast in 14 IPAA patients and in 12 healthy control subjects. Results: Basal PYY was slightly lower in the IPAA patients than in the controls (8.3 ± 0.3 versus 9.3 ± 1.1 pM; not significant). Ingestion of the meal induced a small but significant increase of PYY to a maximum of 10.9 ± 0.9 pM in patients. Integrated postprandial PYY was markedly reduced in patients when compared with the controls (1725 ± 66 pM*180 min versus 3194 ± 480 pM*180 min; P < 0.005). Plasma PYY concentrations were inversely correlated with plasma CCK concentrations in the 2nd and 3rd h after the meal (r = -0.86; P = 0.0001). Conclusion: PYY release in response to meal ingestion is markedly reduced but not completely absent in patients with proctocolectomy and ileal pouch-anal anastomosis. The inverse relationship between circulating PYY and CCK in the late postprandial phase is compatible with a negative feedback regulation of CCK release by endogenous PYY. [ABSTRACT FROM AUTHOR]

Impaired postprandial gallbladder emptying in celiac disease has been attributed to an absence of appropriate cholecystokinin release. To determine if a flat jejunal mucosa in celiac patients is related to a reduced cholecystokinin-secreting capacity, increasing doses of bombesin were infused into six patients with celiac disease and a flat jejunal mucosa (group A), in seven celiac patients with a normal jejunal mucosa while on a gluten-free diet (group B), and in seven healthy controls (group C). Bombesin induced significant (P < 0.05) increments of plasma CCK to a maximum value of 1.0 +/- 0.3 pM in group A, to 1.5 +/- 0.3 pM in group B, and to 1.2 +/- 0.3 pM in group C (NS between groups), that were accompanied by significant (P < 0.05) gallbladder emptying responses of 70 +/- 4% in group A, 47 +/- 10% in group B and 65 +/- 5% in group C. Dose-response relationships were not different between groups. We conclude that there is no major impairment of gallbladder responsiveness to bombesin or of cholecystokinin-secreting capacity in patients with a flat jejunal mucosa due to celiac disease. [ABSTRACT FROM AUTHOR]