Gardner, Timothy B.

Goals: Describe the establishment and expansion of a global gastrointestinal (GI) partnership and its impact on the advancement of GI care in Rwanda. Background: GI disease disproportionately affects low- and middle-income countries. In Rwanda, governmental and nonprofit efforts have made significant progress in expanding access to health care in the wake of the 1994 genocide; however, specialized care remains largely unrecognized or inaccessible. In response, the Rwanda Ministry of Health established a partnership with an international gastroenterology NGO to address this critical need. Study: We present summative data generated by this partnership. To inform future global GI programs, we provide lessons learned and details about Rwanda’s successful establishment of an in-country, self-sustainable, and locally governed gastroenterology training program. Results: From 2017 to 2023, the partnership expanded the number of clinical sites receiving care from 4 to 11. Total procedural volume increased from 244 to 1069. Most common presenting upper GI symptoms included dyspepsia, reflux, and emesis, while most common lower GI symptoms included hematochezia and constipation. Since 2017, this partnership has increased the number of faculty volunteering in Rwanda (and Rwandan clinicians studying in US academic medical centers), expanded its geographical reach, assisted in the creation of a GI fellowship, and enabled Rwanda to become an East African hub for medical education. Conclusions: Lessons learned across ethical, financial, leadership, cultural, and medical domains from the successful establishment and expansion of an international GI partnership in Rwanda provides invaluable insights to guide development of future models of health care in emerging economies.

INTRODUCTION: Prophylactic pancreatic stent placement (PSP) is effective for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk cases, but the optimal technical approach to this intervention remains uncertain. METHODS: In this secondary analysis of 787 clinical trial patients who underwent successful stent placement, we studied the impact of (i) whether pancreatic wire access was achieved for the sole purpose of PSP or naturally during the conduct of the case, (ii) the amount of effort expended on PSP, (iii) stent length, (iv) stent diameter, and (v) guidewire caliber. We used logistic regression models to examine the adjusted association between each technical factor and post-ERCP pancreatitis (PEP). RESULTS: Ninety-one of the 787 patients experienced PEP. There was no clear association between PEP and whether pancreatic wire access was achieved for the sole purpose of PSP (vs occurring naturally; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.37–1.84), whether substantial effort expended on stent placement (vs nonsubstantial effort; OR 1.58, 95% CI 0.73–3.45), stent length (>5 vs ≤5 cm; OR 1.01, 95% CI 0.63–1.61), stent diameter (≥5 vs <5 Fr; OR 1.13, 95% CI 0.65–1.96), or guidewire caliber (0.035 vs 0.025 in; 0.83, 95% CI 0.49–1.41). DISCUSSION: The 5 modifiable technical factors studied in this secondary analysis of large-scale randomized trial data did not appear to have a strong impact on the benefit of prophylactic PSP in preventing PEP after high-risk ERCP. Within the limitations of post hoc subgroup analysis, these findings may have important implications in procedural decision making and suggest that the benefit of PSP is robust to variations in technical approach.

Acute pancreatitis (AP), defined as acute inflammation of the pancreas, is one of the most common diseases of the gastrointestinal tract leading to hospital admission in the United States. It is important for clinicians to appreciate that AP is heterogenous, progressing differently among patients and is often unpredictable. While most patients experience symptoms lasting a few days, almost one-fifth of patients will go on to experience complications, including pancreatic necrosis and/or organ failure, at times requiring prolonged hospitalization, intensive care, and radiologic, surgical, and/or endoscopic intervention. Early management is essential to identify and treat patients with AP to prevent complications. Patients with biliary pancreatitis typically will require surgery to prevent recurrent disease and may need early endoscopic retrograde cholangiopancreatography if the disease is complicated by cholangitis. Nutrition plays an important role in treating patients with AP. The safety of early refeeding and importance in preventing complications from AP are addressed. This guideline will provide an evidence-based practical approach to the management of patients with AP.

INTRODUCTION: Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are progressive inflammatory syndromes with variable features. Pain is the primary feature that contributes to low physical and mental quality of life with a third of patients reporting severe pain. Pain experience is worsened by depression. Here, we tested the hypothesis that genetic risk of the psychiatric conditions of anxiety and post-traumatic stress disorder (PTSD) is associated with pain in CP and RAP + CP subjects. METHODS: The study cohort included phenotyped and genotyped RAP and CP patients from the North American Pancreatitis Study II of European Ancestry. Candidate genetic association studies were based on the absence of pain vs pain that is constant, constant-severe, or severe. Twenty-eight candidate genetic loci for anxiety and PTSD risk were identified in the literature and were the focus of this study. RESULTS: We identified 24 significant pain-associated single nucleotide polymorphisms within 13 loci across the 3 pain patterns in CP and RAP + CP ( P < 0.002). Thirteen anxiety or PTSD genes were within these pain loci indicating nonrandom associations ( P < 4.885 × 10 −23 ). CTNND2 was associated with all pain categories and all pancreatitis etiologies. Implicated systems include neuronal signaling ( HTR2A , DRD3 , NPY , and BDNF ), hypothalamic-pituitary-adrenal axis ( NR3C1 and FKBP5 ), and cell-cell interaction ( CTNND2 and THBS2 ). DISCUSSION: A component of constant and severe pain in patients with RAP and CP is associated with genetic predisposition to anxiety and PTSD. Identification of patients at risk eligible for trials of targeted treatment as a component of a multidisciplinary pain management strategy should be formally evaluated.

Introduction: Diabetes mellitus (DM) is a complication of chronic pancreatitis (CP). Whether pancreatogenic diabetes associated with CP-DM represents a discrete pathophysiologic entity from type 2 DM (T2DM) remains uncertain. Addressing this question is needed for development of specific measures to manage CP-DM. We approached this question from a unique standpoint, hypothesizing that if CP-DM and T2DM are separate disorders, they should be genetically distinct. To test this hypothesis, we sought to determine whether a genetic risk score (GRS) based on validated single nucleotide polymorphisms for T2DM could distinguish between groups with CP-DM and T2DM. Methods: We used 60 T2DM single nucleotide polymorphisms to construct a weighted GRS in 1,613 subjects from the North American Pancreatitis Study 2 and 2,685 subjects from the Multi-Ethnic Study of Atherosclerosis, all of European origin. Results: The mean GRS was identical between 321 subjects with CP-DM and 423 subjects with T2DM (66.53 vs 66.42, P = 0.95), and the GRS of both diabetic groups was significantly higher than that of nondiabetic controls (n = 3,554, P < 0.0001). Exploratory analyses attempting to enrich the CP-DM group for pancreatogenic diabetes, such as eliminating diabetes diagnosed before CP, requiring pancreas-specific comorbidities, or removing those with a family history of diabetes, did not improve the ability of the GRS to distinguish between CP-DM and T2DM. Discussion: Recognizing that we lacked a gold standard to define CP-DM, our study suggests that CP-DM may be a subtype of T2DM, a notion that should be tested in future, large prospective studies.

INTRODUCTION: Detailed recommendations and guidelines for acute pancreatitis (AP) management currently exist. However, quality indicators (QIs) are required to measure performance in health care. The goal of the Acute Pancreatitis Task Force on Quality was to formally develop QIs for the management of patients with known or suspected AP using a modified version of the RAND/UCLA Appropriateness Methodology. METHODS: A multidisciplinary expert panel composed of physicians (gastroenterologists, hospitalists, and surgeons) who are acknowledged leaders in their specialties and who represent geographic and practice setting diversity was convened. A literature review was conducted, and a list of proposed QIs was developed. In 3 rounds, panelists reviewed literature, modified QIs, and rated them on the basis of scientific evidence, bias, interpretability, validity, necessity, and proposed performance targets. RESULTS: Supporting literature and a list of 71 proposed QIs across 10 AP domains (Diagnosis, Etiology, Initial Assessment and Risk Stratification, etc.) were sent to the expert panel to review and independently rate in round 1 (95% of panelists participated). Based on a round 2 face-to-face discussion of QIs (75% participation), 41 QIs were classified as valid. During round 3 (90% participation), panelists rated the 41 valid QIs for necessity and proposed performance thresholds. The final classification determined that 40 QIs were both valid and necessary. DISCUSSION: Hospitals and providers managing patients with known or suspected AP should ensure that patients receive high-quality care and desired outcomes according to current evidence-based best practices. This physician-led initiative formally developed 40 QIs and performance threshold targets for AP management. Validated QIs provide a dependable quantitative framework for health systems to monitor the quality of care provided to patients with known or suspected AP.

ABSTRACTObjectives:The aim of the present study was to investigate the natural history of chronic pancreatitis (CP); patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared.Methods:Demographics, risk factors, disease duration, management and outcomes of 224 children and 1063 adults were compared using appropriate statistical tests for categorical and continuous variables.Results:Alcohol was a risk in 53% of adults and 1% of children (P < 0.0001); tobacco in 50% of adults and 7% of children (P < 0.0001). Obstructive factors were more common in children (29% vs 19% in adults, P = 0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, P = 0.107). Diabetes was more common in adults than children (36% vs 4% respectively, P < 0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2‐CO) were compared with INSPPIRE subjects. These 2 cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2‐CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2‐CO vs 1% INSPPIRE cohorts, P = 0.011).Conclusions:Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.