Topazian, Mark

Abstract Background and study aims Adequacy of endoscope disinfection in resource-limited settings is unknown. Adenosine triphosphate (ATP) testing is useful for evaluation of endoscope reprocessing, and ATP <200 relative light units (RLUs) after manual endoscope cleaning has been associated with adequacy of endoscope disinfection. Methods Consecutive endoscopes undergoing reprocessing at five World Gastroenterology Organisation (WGO) training centers underwent ATP testing before and after an on-site educational intervention designed to optimize reprocessing practices. Results A total of 343 reprocessing cycles of 65 endoscopes were studied. Mean endoscope age was 5.3 years (range 1–13 years). Educational interventions, based on direct observation of endoscope reprocessing practices at each site, included refinements in pre-cleaning, manual cleaning, high-level disinfection, and endoscope drying and storage. The percentage of reprocessing cycles with post-manual cleaning ATP ≧200 decreased from 21.4% prior to educational intervention to 14.8% post-intervention (P=0.11). In multivariable logistic modelling, gastroscopes were significantly less likely (odds ratio [OR] 0.04, 95% confidence interval [CI] 0.01–0.19; P<0.001) than colonoscopes to achieve post-manual cleaning ATP < 200. No other factor (educational intervention, study site, endoscope age) was significantly associated with improved outcomes. Endoscope ID was not significantly associated with ATP values, and sites that performed manual versus automated HLD did not have significantly different likelihood of post-manual cleaning ATP <200 (OR 1.18, 95% CI 0.56–2.50; P=0.67). Conclusions In resource-limited settings, approximately 20% of endoscope reprocessing cycles may result in inadequate disinfection. This was not significantly improved by a comprehensive educational intervention. Alternative approaches to endoscope reprocessing are needed.

Objectives Chronic pancreatitis (CP) is a chronic fibroinflammatory condition of the pancreas difficult to diagnose in early stages. Novel biomarkers useful to facilitate early diagnosis or treatment responses may be found in biofluids. Although saliva can be easily and noninvasively collected from patients, useful salivary biomarkers from CP patients have not yet been identified. Methods Here, we analyzed the proteome by quantitative proteomics, cytokine/chemokine levels by Luminex analysis, prostaglandin E2 (PGE2) levels by a mass spectrometry-based assay, and bacterial species diversity by 16S ribosomal ribonucleic acid sequencing in saliva samples from confirmed CP patients and healthy controls. Results Our results indicate the presence of various differentially expressed proteins, cytokines/chemokines, and a loss of oral bacterial diversity in the saliva of CP patients. The PGE2 levels trend toward elevation in CP patients. Area under the receiver operating characteristic curve models for proteomic, cytokine, and PGE2 assays ranged from 0.59 to 0.90. Conclusions Collectively, our studies identify a range of putative CP biomarkers and alterations in human saliva requiring further validation. The biomarker discovery approaches we used might lead to identification of biomarkers useful for CP diagnosis and monitoring.

Abstract Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N = 681) with CP, 80% experienced abdominal pain within the year before enrollment. Subjects who experienced pain in the week before enrollment (N = 391) completed PROMIS Neuropathic and Nociceptive Pain Quality instruments which were then used to classify them by pain type: 40% had nociceptive, 5% had neuropathic-like, and 32% had both types of pain. The prevalence of having both types of pain was higher among women and subjects with diabetes mellitus, whereas nociceptive-only pain was more prevalent among men and those with pancreatic duct stricture. Other factors, including pain medication use and healthcare utilization, did not differ between groups based on pain type. Subjects in the Both group had significantly worse health and QoL scores relative to those with nociceptive-only pain, suggesting that using psychosocial pain surveys may be useful for understanding pain subtypes in patients with CP. Additional research is needed to identify biochemical and biophysical signatures that may associate with and predict responses to mechanism-specific interventions.

Background: Primary sclerosing cholangitis (PSC) is a major risk factor for cholangiocarcinoma (CCA). We investigated biliary and fecal microbiota to determine whether specific microbes in the bile or stool are associated with PSC or CCA. Methods: Bile was obtained from 32 patients with PSC, 23 with CCA with PSC, 26 with CCA without PSC, and 17 controls. Over 90% of bile samples were from patients with perihilar CCA. Stool was obtained from 31 patients with PSC (11 were matched to bile), 16 with CCA with PSC (10 matched to bile), and 11 with CCA without PSC (6 matched to bile). Microbiota composition was assessed using 16SrRNA-marker-based sequencing and was compared between groups. Results: Bile has a unique microbiota distinguished from negative DNA controls and stool. Increased species richness and abundance of Fusobacteria correlated with duration of PSC and characterized the biliary microbiota in CCA. Stool microbiota composition showed no significant differences between groups. Conclusions: We identified a unique microbial signature in the bile of patients with increased duration of PSC or with CCA, suggesting a role for microbiota-driven inflammation in the pathogenesis and or progression to perihilar CCA. Further studies are needed to test this hypothesis.

Abstract Background and study aims Dysphagia from esophageal cancer may be palliated with self-expanding metallic stents (SEMS). Controversy exists about the use of dilation before SEMS deployment. Patients and methods We performed a retrospective cohort study of patients who had SEMS placement without fluoroscopy for palliation at Tenwek Hospital in Bomet, Kenya between January 1999 and April 2019. The primary outcome was any serious adverse event (AE) (chest pain, stent migration, perforation, bleeding, or all-cause mortality) within 30 days of the procedure. Various demographic and clinical characteristics, and procedural details, were examined as risk factors. Technical success, defined as correct SEMS placement, and clinical success, defined as dysphagia score improvement without 30-day mortality, were examined. Results A total of 3823 patients underwent SEMS placement, with 2844 (74.4 %) placed in the second decade of the study. Technical and clinical success were achieved in 97.2 % and 95.5 %, respectively, with mean dysphagia scores improving from 3.4 (SD 0.6) to 0.9 (SD 1.3) post-stent placement. AEs occurred in 169 patients (4.4 %). AEs, specifically perforations, were associated with dilation to greater than 36F in the first decade. Perforation rates decreased from the first (4.1 %) to the second decade (0.2 %). Only 30% had complete 30-day follow-up data. Conclusions SEMS placement is a safe, effective method of palliating malignant dysphagia, with low rates of AEs and 30-day mortality and high rates of clinical and technical success. Dilation can facilitate placement of SEMS without fluoroscopy but should not be performed above 36F due to the risk of perforation.

Abstract Background and study aims Limited evidence suggests that endoscopy capacity in sub-Saharan Africa is insufficient to meet the levels of gastrointestinal disease. We aimed to quantify the human and material resources for endoscopy services in eastern African countries, and to identify barriers to expanding endoscopy capacity. Patients and methods In partnership with national professional societies, digestive healthcare professionals in participating countries were invited to complete an online survey between August 2018 and August 2020. Results Of 344 digestive healthcare professionals in Ethiopia, Kenya, Malawi, and Zambia, 87 (25.3 %) completed the survey, reporting data for 91 healthcare facilities and identifying 20 additional facilities. Most respondents (73.6 %) perform endoscopy and 59.8 % perform at least one therapeutic modality. Facilities have a median of two functioning gastroscopes and one functioning colonoscope each. Overall endoscopy capacity, adjusted for non-response and additional facilities, includes 0.12 endoscopists, 0.12 gastroscopes, and 0.09 colonoscopes per 100,000 population in the participating countries. Adjusted maximum upper gastrointestinal and lower gastrointestinal endoscopic capacity were 106 and 45 procedures per 100,000 persons per year, respectively. These values are 1 % to 10 % of those reported from resource-rich countries. Most respondents identified a lack of endoscopic equipment, lack of trained endoscopists and costs as barriers to provision of endoscopy services. Conclusions Endoscopy capacity is severely limited in eastern sub-Saharan Africa, despite a high burden of gastrointestinal disease. Expanding capacity requires investment in additional human and material resources, and technological innovations that improve the cost and sustainability of endoscopic services.

The benefit of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of primary sclerosing cholangitis (PSC) remains controversial. To identify predictors of jaundice resolution after ERCP and whether resolution is associated with improved patient outcomes, we conducted a retrospective cohort study of 124 patients with jaundice and PSC. These patients underwent endoscopic biliary balloon dilation and/or stent placement at an American tertiary center, with validation in a separate cohort of 102 patients from European centers. Jaundice resolved after ERCP in 52% of patients. Median follow‐up was 4.8 years. Independent predictors of jaundice resolution included older age (P = 0.048; odds ratio [OR], 1.03 for every 1‐year increase), shorter duration of jaundice (P = 0.059; OR, 0.59 for every 1‐year increase), lower Mayo Risk Score (MRS) (P = 0.025; OR, 0.58 for every 1‐point increase), and extrahepatic location of the most advanced biliary stricture (P = 0.011; OR, 3.13). A logistic regression model predicted jaundice resolution with area under the receiver operator characteristic curve of 0.67 (95% confidence interval, 0.5‐0.79) in the validation set. Independent predictors of death or transplant during follow‐up included higher MRS at the time of ERCP (P < 0.0001; hazard ratio [HR], 2.33 for every 1‐point increase), lower total serum bilirubin before ERCP (P = 0.031; HR, 0.91 for every 1 mg/dL increase), and persistence of jaundice after endoscopic therapy (P = 0.003; HR, 2.30). Conclusion: Resolution of jaundice after endoscopic treatment of biliary strictures is associated with longer transplant‐free survival of patients with PSC. The likelihood of resolution is affected by demographic, hepatic, and biliary variables and can be predicted using noninvasive data. These findings may refine the use of ERCP in patients with jaundice with PSC.

INTRODUCTION: Severe abdominal pain is a cardinal symptom of chronic pancreatitis (CP) associated with a high economic and societal burden. In other chronic pain conditions, cognitive-behavioral therapy (CBT) has demonstrated efficacy in improving patient outcomes (e.g., pain-related disability and depression). However, CBT has not yet been evaluated in adult patients with painful CP. We aimed to (i) evaluate the feasibility and acceptability of an adapted Internet CBT program for CP and (ii) generate pilot data regarding the effects of treatment on patient pain outcomes. METHODS: Thirty adults (mean age = 49.8 years, SD = 12.5; 80% women) with suspected or definite CP were randomized to Internet CBT (Pancreatitis Pain Course) versus control. The Pancreatitis Pain Course has 5 CBT lessons (e.g., thought challenging, relaxation, and activity pacing) delivered over 8 weeks. Pain interference, pain intensity, and quality of life were assessed at pretreatment, posttreatment, and the 3-month follow-up. Qualitative interviews were conducted at posttreatment with a subset of participants. RESULTS: Eighty percent of participants rated the program as highly acceptable; 64.3% completed all 5 lessons. Qualitative data revealed positive perceptions of program features, relevancy, and skills. Patients randomized to Internet CBT demonstrated moderate to large effects in reducing pain intensity and pain interference from baseline to 3 months. The proportion of treatment responders (>30% improvement) was significantly greater in the Internet-CBT group than in the control group (50% vs 13%, Fisher exact t test P = 0.04). DISCUSSION: In this first trial of CBT pain self-management in CP, feasibility, acceptability, and preliminary efficacy for reducing pain and disability were demonstrated. Future definitive trials of CBT are needed.

PURPOSE The eastern corridor of Africa is affected by a high burden of esophageal cancer (EC), with > 90% of patients presenting with advanced disease. Self-expanding metal stents (SEMS) have been previously reported as safe and effective for palliation of malignant dysphagia in resource-limited settings; however, access is limited throughout Eastern Africa. METHODS In response to demand for palliative interventions for patients with dysphagia because of EC, the African Esophageal Cancer Consortium (AfrECC) partnered with the Clinton Health Access Initiative to improve access to SEMS in Eastern Africa. We undertook a stepwise implementation approach to (1) identify barriers to SEMS access, (2) conduct a market analysis, (3) select an industry partner, (4) establish regulatory and procurement processes, (5) develop endoscopic training resources, (6) create a medical device registry, and (7) establish principles of accountability. RESULTS Following an evaluation of market demand and potential SEMS manufacturers, Boston Scientific Corporation announced its commitment to launch an access program to provide esophageal SEMS to patients in Tanzania, Kenya, Malawi, and Zambia at a subsidized price. Parallel regulatory and procurement processes were established in each participating country. Endoscopy training courses were designed and conducted, using the Training-of-Trainers model. A device registry was created to centralize data for quality control and to monitor channels of SEMS distribution. Principles of accountability were developed to guide the sustainability of this endeavor. CONCLUSION The AfrECC Stent Access Initiative is an example of a multisector partnership formed to provide an innovative solution to align regional needs with a supply chain for a high-priority medical device.