Circulating immune signatures in chronic pancreatitis with and without preceding acute pancreatitis: A pilot study.

OBJECTIVE: To investigate profiles of circulating immune signatures in healthy controls and chronic pancreatitis patients (CP) with and without a preceding history of acute pancreatitis (AP). METHODS: We performed a phase 1, cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies (PROCEED) study. All samples were collected during a clinically quiescent phase. CP subjects were categorized into two subgroups based on preceding episode(s) of AP. Healthy controls were included for comparison. Blinded samples were analyzed using an 80-plex Luminex assay of cytokines, chemokines, and adhesion molecules. Group and pairwise comparisons of analytes were performed between the subgroups. RESULTS: In total, 133 patients with CP (111 with AP and 22 without AP) and 50 healthy controls were included. Among the 80 analytes studied, CP patients with a history of AP had significantly higher serum levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-8, IL-1 receptor antagonist, IL-15) and chemokines (Cutaneous T-Cell Attracting Chemokine (CTACK), Monokine induced Gamma Interferon (MIG), Macrophage-derived Chemokine (MDC), Monocyte Chemoattractant Protein-1 (MCP-1)) compared to CP without preceding AP and controls. In contrast, CP patients without AP had immune profiles characterized by low systemic inflammation and downregulation of anti-inflammatory mediators, including IL-10. CONCLUSION: CP patients with a preceding history of AP have signs of systemic inflammatory activity even during a clinically quiescent phase. In contrast, CP patients without a history of AP have low systemic inflammatory activity. These findings suggest the presence of two immunologically diverse subtypes of CP.

Assessment of endoscope reprocessing at World Gastroenterology Organisation training centers using adenosine triphosphate testing.

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.

Circulating immune signatures across clinical stages of chronic pancreatitis: a pilot study.

OBJECTIVE: This pilot study seeks to identify serum immune signatures across clinical stages of patients with chronic pancreatitis (CP). METHODS: We performed a cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies-study. CP subjects were categorised into three clinical stages based on the presence/absence of metabolic complications: (1) CP with no diabetes and exocrine pancreatic dysfunction (EPD), (2) CP with either diabetes or EPD, and (3) CP with diabetes and EPD. Blinded samples were analysed using an 80-plex Luminex assay of cytokines/chemokines/adhesion molecules. Group and pairwise comparisons were performed to characterise immune signatures across CP subgroups. RESULTS: A total of 135 CP subjects (evenly distributed between clinical stages) and 50 controls were studied. Interleukin-6 (IL-6), interleukin-8 (IL-8), and soluble intercellular adhesion molecule 1 (sICAM-1) were significantly elevated in CP subjects compared to controls. The levels of IL-6 and IL-8 increased with advancing disease stages, with the highest levels observed in CP with diabetes and EPD (clinical stage 3). Furthermore, hepatocyte growth factor and macrophage-derived chemokine were significantly increased in clinical stage 3 compared to controls. CONCLUSION: Our study reveals a progressive elevation in pro-inflammatory cytokines and chemokines with advancing clinical stages of CP. These findings indicate potential targets for the development of disease-modifying interventions.

Lumen-apposing metal stents with or without coaxial plastic stent placement for the management of pancreatic fluid collections.

BACKGROUND AND AIMS: Coaxial double-pigtail plastic stent (DPPS) placement is often performed within lumen-apposing metal stents (LAMSs) for drainage of pancreatic fluid collections (PFCs) to prevent adverse events (AEs) such as stent occlusion and bleeding. This study compares the safety and outcomes of LAMSs alone versus LAMSs with coaxial DPPSs for PFC management. METHODS: Patients undergoing drainage of a PFC with LAMSs were retrospectively identified and categorized as LAMS or LAMS/DPPS based on initial drainage strategy. The AE rate, AE type, and clinical success were extracted by chart review. RESULTS: One hundred eighty-five individuals (83 LAMS, 102 LAMS/DPPS) were identified. No significant differences were found in rates of clinical success (75.9% LAMS vs 69.6% LAMS/DDPS, P = .34) or overall AEs (15.7% LAMS vs 15.7% LAMS/DPPS, P = .825). CONCLUSIONS: In this comparative single-center study, placement of a coaxial DPPS for drainage of PFCs with LAMSs did not affect rates of AEs or clinical success.

Serum Biomarkers of Nociceptive and Neuropathic Pain in Chronic Pancreatitis.

Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for nonopioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were compared between CP subjects with and without pain. Only platelet-derived growth factor B (PDGF-B) stood out, with levels significantly higher in the CP pain group as compared to subjects with no pain. Subjects with pain were then stratified into 4 pain subtypes (Neuropathic, Nociceptive, Mixed, and Unclassified). A comparison of putative biomarker concentration among 5 groups (no pain and 4 pain subtypes) identified unique proteins that were correlated with pain subtypes. Serum transforming growth factor beta 1 (TGFß1) level was significantly higher in the Nociceptive pain group compared to the No pain group, suggesting that TGFß1 may be a biomarker for nociceptive pain. The Neuropathic pain only group was too small to detect statistical differences. However, glycoprotein 130 (GP130), a coreceptor for interleukin 6, was significantly higher in the Mixed pain group compared to the groups lacking a neuropathic pain component. These data suggest that GP130 may be a biomarker for neuropathic pain in CP. PERSPECTIVE: Serum TGFß1 and GP130 may be biomarkers for nociceptive and neuropathic CP pain, respectively. Preclinical data suggest inhibiting TGFß1 or GP130 reduces CP pain in rodent models, indicating that additional translational and clinical studies may be warranted to develop a precision medicine approach to the management of pain in CP.

A Protocolized Management of Walled-Off Necrosis (WON) Reduces Time to WON Resolution and Improves Outcomes.

BACKGROUND AND AIMS: Patients with infected or symptomatic walled-off necrosis (WON) have high morbidity and health care utilization. Despite the recent adoption of nonsurgical treatment approaches, WON management remains nonalgorithmic. We investigated the impact of a protocolized early necrosectomy approach compared with a nonprotocolized, clinician-driven approach on important clinical outcomes. METHODS: Records were reviewed for consecutive patients with WON who underwent a protocolized endoscopic drainage with a lumen-apposing metal stent (cases), and for patients with WON treated with a lumen-apposing metal stent at the same tertiary referral center who were not managed according to the protocol (control subjects). The protocol required repeat cross-sectional imaging within 14 days after lumen-apposing metal stent placement, with regularly scheduled endoscopic necrosectomy if WON diameter reduction was <50%. Control patients were treated according to their clinician's preference without an a priori strategy. Inverse probability of treatment weighting-adjusted analysis was used to evaluate the influence of being in the protocolized group on time to resolution. RESULTS: A total of 24 cases and 47 control subjects were included. There were no significant differences in baseline characteristics. Although numbers of endoscopies and necrosectomies were similar, cases had lower adverse event rates, shorter intensive care unit stay, and required nutritional support for fewer days. On matched multivariate Cox regression, cases had earlier WON resolution (hazard ratio, 5.73; 95% confidence interval, 2.62-12.5). This was confirmed in the inverse probability of treatment weighting-adjusted analysis (hazard ratio, 3.4; 95% confidence interval, 1.92-6.01). CONCLUSIONS: A protocolized strategy resulted in faster WON resolution compared with a discretionary approach without the need for additional therapeutic interventions, and with a better safety profile and decreased health care utilization.

Distinct Serum Immune Profiles Define the Spectrum of Acute and Chronic Pancreatitis From the Multicenter Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) Study.

BACKGROUND & AIMS: Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and progressing in some cases to recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). Currently, there are no approved therapies or early diagnostic or prognostic biomarkers for pancreatitis. The current study examined whether patient serum immune profiling could identify noninvasive biomarkers and provide mechanistic insight into the disease continuum of pancreatitis. METHODS: Using Olink immunoassay, we assessed the protein levels of 92 immune markers in serum samples from participants enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study of the Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) consortium. Samples (N = 231) were obtained from individuals without pancreatic disease (n = 56) and from those with chronic abdominal pain (CAP) (n = 24), AP (n = 38), RAP (n = 56), and CP (n = 57). RESULTS: A total of 33 immune markers differentiated the combined pancreatitis groups from controls. Immune markers related to interleukin (IL) 17 signaling distinguished CP from AP and RAP. Similarly, the serum level of IL17A and C-C motif chemokine ligand 20 differentiated CP from CAP, suggesting the involvement of T helper 17 cells in CP pathogenesis. The receiver operator characteristic curve with 2 immune markers (IL17A and sulfotransferase 1A1) could differentiate CP from CAP (optimistic area under the curve = 0.78). The macrophage classical activation pathway elevated along the continuum of pancreatitis, suggesting an accumulation of proinflammatory signals over disease progression. Several immune markers were associated with smoking, alcohol, and diabetes status. CONCLUSIONS: Immune profiling of serum samples from a large pancreatitis cohort led to identifying distinct immune markers that could serve as potential biomarkers to differentiate the varying pancreatitis disease states. In addition, the finding of IL17 signaling in CP could provide insight into the immune mechanisms underlying disease progression.

The interventional direct peroral cholangioscopy toolbox for endoscopic snare resection of a high-grade biliary intraductal neoplasia.

Video 1Demonstration of techniques for performing direct peroral cholangioscopy.

Novel classification system for walled-off necrosis: a step toward standardized nomenclature and risk-stratification framework.

BACKGROUND AND AIMS: The optimal therapeutic approach for walled-off necrosis (WON) is not fully understood, given the lack of a validated classification system. We propose a novel and robust classification system based on radiologic and clinical factors to standardize the nomenclature, provide a framework to guide comparative effectiveness trials, and inform the optimal WON interventional approach. METHODS: This was a retrospective analysis of patients who underwent endoscopic management of WON by lumen-apposing metal stent placement at a tertiary referral center. Patients were classified according to the proposed QNI classification system: quadrant ("Q"), represented an abdominal quadrant distribution; necrosis ("N"), denoted by the percentage of necrosis of WON; and infection ("I"), denoted as positive blood culture and/or systemic inflammatory response syndrome reaction with a positive WON culture. Two blinded reviewers classified all patients according to the QNI system. Patients were then divided into 2 groups: those with a lower QNI stratification (≤2 quadrants and ≤30% necrosis; group 1) and those with a higher stratification (≥3 quadrants, 2 quadrants with ≥30% necrosis, or 1 quadrant with >60% necrosis and infection; group 2). The primary outcome was mean time to WON resolution. Secondary procedural and clinical outcomes between the groups were compared. RESULTS: Seventy-one patients (75% men) were included and stratified by the QNI classification; group 1 comprised 17 patients and group 2, 54 patients. Patients in group 2 had a higher number of necrosectomies, longer hospital stays, and more readmissions. The mean time to resolution was longer in group 2 than in group 1 (79.6 ± 7.76 days vs 48.4 ± 9.22 days, P = .02). The mortality rate was higher in group 2 (15% vs 0%, P = .18). CONCLUSIONS: Despite the heterogeneous nature of WON in severe acute pancreatitis, a proposed QNI system may provide a standardized framework for WON classification to inform clinical trials, risk-stratify the disease course, and potentially inform an optimal management approach.

Association of Chronic Pancreatitis Pain Features With Physical, Mental, and Social Health.

BACKGROUND AND AIMS: Pain is a cardinal symptom of chronic pancreatitis (CP). Using Patient-Reported Outcomes Measurement Information System (PROMIS) measures, we characterized physical and mental health and symptom profiles of a well-defined cohort of individuals with CP and compared them with control subjects. Among patients with CP, we also examined associations between pain (intensity, temporal nature) and PROMIS symptom profiles and the prevalence of clinically significant psychological comorbidities. METHODS: We analyzed baseline data in 488 CP patients and 254 control subjects enrolled in PROCEED (Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies), an ongoing longitudinal cohort study. Participants completed the PROMIS-Global Health, which captures global physical and mental health, and the PROMIS-29 profile, which captures 7 symptom domains. Self-reported pain was categorized by severity (none, mild-moderate, severe) and temporal nature (none, intermittent, constant). Demographic and clinical data were obtained from the PROCEED database. RESULTS: Pain was significantly associated with impairments in physical and mental health. Compared with participants with no pain, CP participants with severe pain (but not mild-moderate pain) had more decrements in each PROMIS domain in multivariable models (effect sizes, 2.54-7.03) and had a higher prevalence of clinically significant depression, anxiety, sleep disturbance, and physical disability (odds ratios, 2.11-4.74). Similar results were noted for constant pain (but not intermittent pain) for PROMIS domains (effect sizes, 4.08-10.37) and clinically significant depression, anxiety, sleep disturbance and physical disability (odds ratios, 2.80-5.38). CONCLUSIONS: Severe and constant pain are major drivers for poor psychological and physical health in CP. Systematic evaluation and management of psychiatric comorbidities and sleep disturbance should be incorporated into routine management of patients with CP. (ClinicalTrials.gov, Number: NCT03099850).

Salivary Biomarker Evaluation of Chronic Pancreatitis Patients Reveals Alterations in Human Proteins, Cytokines, Prostaglandin E2 Levels, and Bacterial Diversity.

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.

Percutaneous transluminal angioplasty balloons for endoscopic ultrasound-guided pancreatic duct interventions.

BACKGROUND: Endoscopic ultrasound (EUS)-guided main pancreatic duct (PD) access may be used when conventional endoscopic retrograde cholangiopancreatography (ERCP) techniques fail. The use of a percutaneous transluminal angioplasty balloon (PTAB), originally developed for vascular interventions, can be used to facilitate transmural (e.g., transgastric) PD access and to dilate high-grade pancreatic strictures. AIM: To describe the technique, efficacy, and safety of PTABs for EUS-guided PD interventions. METHODS: Patients who underwent EUS with use of a PTAB from March 2011 to August 2021 were retrospectively identified from a tertiary care medical center supply database. PTABs included 3-4 French angioplasty catheters with 3-4 mm balloons designed to use over a 0.018-inch guidewire. The primary outcome was technical success. Secondary outcomes included incidence of adverse events (AEs) and need for early reintervention. RESULTS: A total of 23 patients were identified (48% female, mean age 55.8 years). Chronic pancreatitis was the underlying etiology in 13 (56.5%) patients, surgically altered anatomy (SAA) with stricture in 7 (30.4%), and SAA with post-operative leak in 3 (13.0%). Technical success was achieved in 20 (87%) cases. Overall AE rate was 26% (n = 6). All AEs were mild and included 1 pancreatic duct leak, 2 cases of post-procedure pancreatitis, and 3 admissions for post-procedural pain. No patients required early re-intervention. CONCLUSION: EUS-guided use of PTABs for PD access and/or stricture management is feasible with an acceptable safety profile and can be considered in patients when conventional ERCP cannulation fails.

Potential Role of Inflammation-Promoting Biliary Microbiome in Primary Sclerosing Cholangitis and Cholangiocarcinoma.

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.

Prevalence of esophageal squamous dysplasia in relatives of patients with esophageal cancer in Southwestern Kenya.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) and its asymptomatic precursor lesion, esophageal squamous dysplasia (ESD), are common in East Africa. It is unknown whether family history of esophageal cancer is a risk factor for both ESD and ESCC in Africa, and whether family members of affected persons should be screened. METHODS: We recruited 296 asymptomatic adult first-degree relatives of ESCC patients residing in southwestern Kenya. Participants completed questionnaires and underwent endoscopy with Lugol's iodine staining and biopsy to determine the prevalence of ESD. Prevalence comparisons were made with a prior population-based cohort from the same catchment area who also underwent Lugol's chromoendoscopy. RESULTS: Mean age was 40.7 years, compared to 62.7 years in the prior population study. The overall prevalence of ESD/ESCC among first-degree relatives was 14.7%, comparable to the background population prevalence of 14.4%, and this comparability remained even after adjusting for the different age distributions of the studies. Post-primary education was the only measured variable that was associated with a decreased risk of ESD/ESCC (adjusted OR=0.31, 95% CI: 0.11, 0.83). There was heterogeneity in the ESD prevalence across families, even after adjustments for varying age and other measured factors. CONCLUSIONS: The prevalence of esophageal squamous dysplasia among first-degree relatives of persons with ESCC was similar to that of the background population of southwestern Kenya; however, there was heterogeneity in ESD prevalence between families, suggesting other genetic or environmental factors may influence family prevalence. Further study of families with a high prevalence of ESD or ESCC is justified.

Prospective Study Assessing Impact of Ethylene Oxide Sterilization on Endoscopic Ultrasound Image Quality.

BACKGROUND & AIMS: Duodenoscope-associated transmission of infections has raised questions about efficacy of endoscope reprocessing using high-level disinfection (HLD). Although ethylene oxide (ETO) gas sterilization is effective in eradicating microbes, the impact of ETO on endoscopic ultrasound (EUS) imaging equipment remains unknown. In this study, we aimed to compare the changes in EUS image quality associated with HLD vs HLD followed by ETO sterilization. METHODS: Four new EUS instruments were assigned to 2 groups: Group 1 (HLD) and Group 2 (HLD + ETO). The echoendoscopes were assessed at baseline, monthly for 6 months, and once every 3 to 4 months thereafter, for a total of 12 time points. At each time point, review of EUS video and still image quality was performed by an expert panel of reviewers along with phantom-based objective testing. Linear mixed effects models were used to assess whether the modality of reprocessing impacted image and video quality. RESULTS: For clinical testing, mixed linear models showed minimal quantitative differences in linear analog score (P = .04; estimated change, 3.12; scale, 0-100) and overall image quality value (P = .007; estimated change, -0.12; scale, 1-5) favoring ETO but not for rank value (P = .06). On phantom testing, maximum depth of penetration was lower for ETO endoscopes (P < .001; change in depth, 0.49 cm). CONCLUSIONS: In this prospective study, expert review and phantom-based testing demonstrated minimal differences in image quality between echoendoscopes reprocessed using HLD vs ETO + HLD over 2 years of clinical use. Further studies are warranted to assess the long-term clinical impact of these findings. In the interim, these results support use of ETO sterilization of EUS instruments if deemed clinically necessary.

High Prevalence of Osteopathy in Chronic Pancreatitis: A Cross-sectional Analysis From the PROCEED Study.

BACKGROUND & AIMS: Chronic pancreatitis (CP) is associated with osteopathy (osteoporosis or osteopenia). However, existing literature is mostly limited to retrospective or administrative studies that have not clearly defined the prevalence and risk factors. Our aim was to identify patient- and disease-related associations with osteopathy in a prospective cohort study of CP. METHODS: We studied 282 subjects with definitive CP enrolled in the PROCEED study who had a baseline dual-energy X-ray absorptiometry (DXA) scan. Osteopenia and osteoporosis were defined using the lowest T-scores. Clinical data were collected using standardized case report forms. Comparisons were performed with a multivariate logistic regression model with forward selection to identify risk factors for osteopathy. RESULTS: The majority of subjects had osteopathy on DXA scan (56.0%; 17.0% osteoporosis; 39.0% osteopenia). Subjects with osteopathy had a higher prevalence of traumatic (40.0% vs 26.4%; P = .02) and spontaneous fractures (3.9% vs 0; P = .04). On multivariate analysis, older age (odds ratio [OR], 1.29 per 5 years; 95% confidence interval [CI], 1.15-1.45), female sex (OR, 3.08; 95% CI, 1.75-5.43), white race (OR, 2.68; 95% CI, 1.20-6.01), and underweight body mass index category (OR, 7.40; 95% CI, 1.56-34.99) were associated with higher probability of osteopathy. There were no significant associations between osteopathy and other patient and disease-related features of CP. CONCLUSION: In the largest study of patients with CP who underwent DXA screening, the majority had osteopathy. There are overlapping risk factors with osteopathy in the general population, but the high prevalence in men and younger women supports the need for future investigations into the mechanisms of bone loss in CP. CLINICALTRIALS: gov number, NCT03099850.

Impact of trimodality sampling on detection of malignant biliary strictures compared with patients with primary sclerosing cholangitis.

BACKGROUND AND AIMS: Malignant biliary strictures can be difficult to diagnose, with up to 20% considered indeterminate after initial tissue sampling. This study aimed to determine the performance characteristics of transpapillary biopsy sampling (TPB) and fluorescence in situ hybridization (FISH) in isolation or in combination with standard brush cytology (BC) in patients who received trimodality sampling for biliary strictures. METHODS: This single-center retrospective cohort study included patients with biliary strictures undergoing ERCP with trimodality sampling between September 2014 and April 2019. Performance characteristics for each diagnostic test alone and in combination were calculated. RESULTS: Two hundred four patients underwent trimodality biliary sampling, including 104 (51.0%) with malignancy. The diagnostic sensitivity for malignancy with BC (17.3%) significantly improved with dual modality (BC+FISH, 58.7%; BC+TPB, 40.4%) or trimodality sampling (68.3%; P < .001 for all comparisons). Trimodality sampling improved diagnostic sensitivity for malignancy compared with BC+FISH (P = .002) and BC+TPB (P < .001). There was no statistically significant difference in the sensitivity of trimodality sampling in detecting cholangiocarcinoma (79.7%) compared with pancreatic cancer (62.5%; P = .1). Among 57 patients with primary sclerosing cholangitis (PSC), the sensitivity of detecting biliary malignancy (n = 20) was 20% for BC and significantly improved with the addition of FISH (80%; P < .001) but not with TPB (35.0%; P = .25). Trimodality sampling did not further improve diagnostic sensitivity (85%) over BC+FISH (80%) for malignancy in the setting of PSC (P = 1). CONCLUSIONS: Trimodality sampling improves the diagnostic sensitivity for the detection of malignant biliary strictures with no significant difference in sensitivity for cholangiocarcinoma compared with pancreatic cancer. However, in patients with PSC, trimodality sampling was not superior to BC+FISH.

Gastrointestinal endoscopy capacity in Eastern Africa.

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.

Internet Cognitive-Behavioral Therapy for Painful Chronic Pancreatitis: A Pilot Feasibility Randomized Controlled Trial.

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.

Endoscopic pancreatic duct stenting for pain palliation in selected pancreatic cancer patients: a systematic review and meta-analysis.

BACKGROUND: Abdominal pain is a debilitating symptom affecting ∼80% of pancreatic cancer (PC) patients. Pancreatic duct (PD) decompression has been reported to alleviate this pain, although this practice has not been widely adopted. We aimed to evaluate the role, efficacy, and safety of endoscopic PD decompression for palliation of PC post-prandial obstructive-type pain. METHODS: A systematic review until 7 October 2020 was performed. Two independent reviewers selected studies, extracted data, and assessed the methodological quality. RESULTS: We identified 12 publications with a total of 192 patients with PC presenting with abdominal pain, in whom PD decompression was attempted, and was successful in 167 patients (mean age 62.5 years, 58.7% males). The use of plastic stents was reported in 159 patients (95.2%). All included studies reported partial or complete improvement in pain levels after PD stenting, with an improvement rate of 93% (95% confidence interval, 79%-100%). The mean duration of pain improvement was 94 ± 16 days. Endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events (AEs) were post-sphincterotomy bleeding (1.8%), post-ERCP pancreatitis (0.6%), and hemosuccus pancreaticus (0.6%). AEs were not reported in two patients who underwent endoscopic ultrasound-guided PD decompression. In the 167 patients with technical success, the stent-migration and stent-occlusion rates were 3.6% and 3.0%, respectively. No AE-related mortality was reported. The methodological quality assessment showed the majority of the studies having low or unclear quality. CONCLUSION: In this exploratory analysis, endoscopic PD drainage may be an effective and safe option in selected patients for the management of obstructive-type PC pain. However, a randomized-controlled trial is needed to delineate the role of this invasive practice.