Diagnosis and Management of Acute Pancreatitis.

Acute pancreatitis (AP) is increasing in incidence across the world, and in all age groups. Major changes in management have occurred in the last decade. Avoiding total parenteral nutrition and prophylactic antibiotics, avoiding overly aggressive fluid resuscitation, initiating early feeding, avoiding endoscopic retrograde cholangiopancreatography in the absence of concomitant cholangitis, same-admission cholecystectomy, and minimally invasive approaches to infected necrosis should now be standard of care. Increasing recognition of the risk of recurrence of AP, and progression to chronic pancreatitis, along with the unexpectedly high risk of diabetes and exocrine insufficiency after AP is the subject of large ongoing studies. In this review, we provide an update on important changes in management for this increasingly common disease.

AGA Clinical Practice Update on the Epidemiology, Evaluation, and Management of Exocrine Pancreatic Insufficiency: Expert Review.

DESCRIPTION: Exocrine pancreatic insufficiency (EPI) is a disorder caused by the failure of the pancreas to deliver a minimum/threshold level of specific pancreatic digestive enzymes to the intestine, leading to the maldigestion of nutrients and macronutrients, resulting in their variable deficiencies. EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately. There is an urgent need to increase awareness of and treatment for this condition. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review was to provide Best Practice Advice on the epidemiology, evaluation, and management of EPI. METHODS: This Expert Review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: EPI should be suspected in patients with high-risk clinical conditions, such as chronic pancreatitis, relapsing acute pancreatitis, pancreatic ductal adenocarcinoma, cystic fibrosis, and previous pancreatic surgery. BEST PRACTICE ADVICE 2: EPI should be considered in patients with moderate-risk clinical conditions, such as duodenal diseases, including celiac and Crohn's disease; previous intestinal surgery; longstanding diabetes mellitus; and hypersecretory states (eg, Zollinger-Ellison syndrome). BEST PRACTICE ADVICE 3: Clinical features of EPI include steatorrhea with or without diarrhea, weight loss, bloating, excessive flatulence, fat-soluble vitamin deficiencies, and protein-calorie malnutrition. BEST PRACTICE ADVICE 4: Fecal elastase test is the most appropriate initial test and must be performed on a semi-solid or solid stool specimen. A fecal elastase level <100 µg/g of stool provides good evidence of EPI, and levels of 100-200 µg/g are indeterminate for EPI. BEST PRACTICE ADVICE 5: Fecal elastase testing can be performed while on pancreatic enzyme replacement therapy. BEST PRACTICE ADVICE 6: Fecal fat testing is rarely needed and must be performed when on a high-fat diet. Quantitative testing is generally not practical for routine clinical use. BEST PRACTICE ADVICE 7: Response to a therapeutic trial of pancreatic enzymes is unreliable for EPI diagnosis. BEST PRACTICE ADVICE 8: Cross-sectional imaging methods (computed tomography scan, magnetic resonance imaging, and endoscopic ultrasound) cannot identify EPI, although they play an important role in the diagnosis of benign and malignant pancreatic disease. BEST PRACTICE ADVICE 9: Breath tests and direct pancreatic function tests hold promise, but are not widely available in the United States. BEST PRACTICE ADVICE 10: Once EPI is diagnosed, treatment with pancreatic enzyme replacement therapy (PERT) is required. If EPI is left untreated, it will result in complications related to fat malabsorption and malnutrition, having a negative impact on quality of life. BEST PRACTICE ADVICE 11: PERT formulations are all derived from porcine sources and are equally effective at equivalent doses. There is a need for H2 or proton pump inhibitor therapy with non-enteric-coated preparations. BEST PRACTICE ADVICE 12: PERT should be taken during the meal, with the initial treatment of at least 40,000 USP units of lipase during each meal in adults and one-half of that with snacks. The subsequent dosage can be adjusted based on the meal size and fat content. BEST PRACTICE ADVICE 13: Routine supplementation and monitoring of fat-soluble vitamin levels are appropriate. Dietary modifications include a low-moderate fat diet with frequent smaller meals and avoiding very-low-fat diets. BEST PRACTICE ADVICE 14: Measures of successful treatment with PERT include reduction in steatorrhea and associated gastrointestinal symptoms; a gain of weight, muscle mass, and muscle function; and improvement in fat-soluble vitamin levels. BEST PRACTICE ADVICE 15: EPI should be monitored and baseline measurements of nutritional status should be obtained (body mass index, quality-of-life measure, and fat-soluble vitamin levels). A baseline dual-energy x-ray absorptiometry scan should be obtained and repeated every 1-2 years.

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.

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.

Utilization of Pancreatic Endotherapy in Patients with Chronic Pancreatitis: Results From a Multicenter Cohort Study in the United States.

BACKGROUND AND AIMS: Although commonly used for treating complications of chronic pancreatitis (CP), data on the frequency and factors associated with the use of pancreatic endotherapy (PET) are limited. Our aim was to define the utilization and factors predictive for receiving PET in a well-characterized CP cohort. METHODS: This is a cross-sectional analysis of data from PROCEED, a multicenter US cohort study of CP. PET modalities primarily consisted of ERCP. A treatment course was defined as the number of sessions performed for a specific indication. A repeat course was defined as PET >1 year after completion of the last course. Multivariable logistic regression identified predictive factors for receiving PET, and proportional rates model assessed risk factors for repeat PET. RESULTS: Of a total of 681 subjects, 238 (34.9%) received PET. Factors associated with receiving PET included female sex (OR: 1.26, 95% CI: 1.03-1.53), lower education (OR: 1.30, 95% CI: 1.04-1.62), income ≤ $50,000 per year (OR: 1.35, 95% CI: 1.07-1.71) and prior acute pancreatitis (AP) (OR: 1.74, 95% CI: 1.31, 2.32). 103/238 subjects (43.3%) underwent repeat PET at a median duration of 2 years with 23.1% receiving 2 courses, 9.7% receiving 3 courses, and 10.4% receiving 4+ courses. CONCLUSIONS: Nearly half of patients with CP who undergo PET received one or more repeat courses within 2-3 years. In addition to a prior history of AP, demographic and socioeconomic factors were associated with receiving PET.

Influence of Butyrate on Impaired Gene Expression in Colon from Patients with High Blood Pressure.

Hypertension (HTN) is associated with gut dysbiosis and the depletion of butyrate-producing bacteria in animal models and people. Furthermore, fecal material transfer from donor hypertensive patients increases blood pressure in normotensive recipient animals and ameliorates HTN-associated pathophysiology. These observations have implications in the impaired interactions between the gut and gut microbiota in HTN. Although this concept is supported in animal models, little is known about human HTN. Therefore, our objective for this study was to compare gene expression with transcriptomics and its potential to influence microbiota in subjects with normal and high blood pressure (HBP). Colon samples from reference subjects with normal blood pressure (REF) and HBP were used for RNA-seq to analyze their transcriptomes. We observed the significant downregulation of gene sets governing immune responses (e.g., SGK1 and OASL), gut epithelial function (e.g., KRT20 and SLC9A3R1), gut microbiota (e.g., PPARG and CIDEC) and genes associated with cardiovascular and gut diseases (e.g., PLAUR and NLN) in HBP subjects; the expression of genes within these pathways correlated with blood pressure. Potential drug targets in the gut epithelium were identified using the Drug Gene International Database for possible use in HTN. They include peroxisome proliferator-activated receptor gamma (PPRG), active serum/glucocorticoid regulated kinase 1 (SGK1) and 3 beta-hydroxysteroid isomerase type II inhibitor (HSD3B). Finally, butyrate, a microbiota-derived short-chain fatty acid, restored the disrupted expression of certain functional genes in colonic organoids from HBP subjects. Patients with HBP exhibit a unique transcriptome that could underlie impaired gut-microbiota interactions. Targeting these interactions could provide a promising new therapeutic intervention for hypertension management.

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.

WITHDRAWN: In Memoriam: Phillip P. Toskes, MD.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1053/j.gastro.2021.07.041. The duplicate article has therefore been withdrawn.

Differences in Age at Onset of Symptoms, and Effects of Genetic Variants, in Patients With Early vs Late-Onset Idiopathic Chronic Pancreatitis in a North American Cohort.

BACKGROUND & AIMS: Idiopathic chronic pancreatitis (ICP) is the second most common subtype of CP. In 1994, researchers reported the bimodal age at onset of ICP symptoms: early onset ICP (EO-ICP; median age, 19.2 y) and late-onset ICP (LO-ICP; median age, 56.2 y). Ages of onset and clinical features of ICP differed from those of alcohol-related CP (ACP). However, variants in PRSS1 had not yet been associated with ICP. We reexamined ages of onset of ICP in a large, North American cohort of patients, and investigated the effects of genetic factors and alcohol use in patients with EO-ICP, LO-ICP, and ACP. METHODS: We performed a cross-sectional analysis of patients with CP of European ancestry enrolled in the North American Pancreatitis Study 2, a prospective study of 1195 patients with CP from 26 centers in the United States from August 2000 through December 2014. We compared age at onset of symptoms for 130 patients with CP who were lifetime abstainers from alcohol (61 patients with early onset and 69 patients with late onset), 308 light to moderate alcohol drinkers with CP, and 225 patients with ACP and heavy to very heavy alcohol use. DNA from available patients was analyzed for variants associated with CP in SPINK1, CFTR, and CTRC. The Kruskal-Wallis test was used to compare continuous variables across groups and based on genetic variants. RESULTS: Median ages at onset of symptoms were 20 years for patients with EO-ICP and no alcohol use, 58 years for patients with LO-ICP and no alcohol use, 47 years for light to moderate alcohol drinkers with CP, and 44 years for patients with ACP. A higher proportion of patients with EO-ICP had constant pain (65%) than patients with LO-ICP (31%) (P = .04). A higher proportion of patients with ACP had pseudocysts (43%) than patients with EO-ICP (11%) (P = .001). A higher proportion of patients with EO-ICP had pathogenic variants in SPINK1, CFTR, or CTRC (49%) than patients with LO-ICP (23%), light to moderate alcohol drinking with CP (26%), or ACP (23%) (P = .001). Among patients with variants in SPINK1, those with EO-ICP had onset of symptoms at a median age of 12 years, and light to moderate alcohol drinkers with CP had an age at onset of 24 years. Among patients with variants in CFTR, light to moderate alcohol drinkers had an age at onset of symptoms of 41 years, but this variant did not affect age at onset of EO-ICP or ACP. CONCLUSIONS: We confirmed previously reported ages at onset of symptoms for EO-ICP and LO-ICP in a North American cohort. We found differences in clinical features among patients with EO-ICP, LO-ICP, and ACP. Almost half of patients with EO-ICP have genetic variants associated with CP, compared with approximately one quarter of patients with LO-CP or ACP. Genetic variants affect ages at onset of symptoms in some groups.

Consortium for the study of chronic pancreatitis, diabetes, and pancreatic cancer: achievements and future directions.

PURPOSE OF REVIEW: To answer several important clinical questions, the Consortium for the study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) research consortium has established several ongoing clinical cohort studies focused on pancreatitis in adults and children, pancreatic cancer, and diabetes associated with pancreatic disease. These will provide a unique resource for clinical and basic science research into these hard-to-treat diseases. RECENT FINDINGS: The cause, natural history, and prognosis of acute relapsing and chronic pancreatitis in adults and children are being delineated. The mechanisms of diabetes associated with chronic pancreatitis, acute pancreatitis, and pancreatic cancer are being defined. The ability to predict the presence of early-stage pancreatic cancer, thought the presence of new-onset diabetes, is being explored as a strategy to improve survival. The CPDPC is now also turning to developing clinically useful biomarkers, and initiating clinical trials in these difficult to treat pancreatic diseases. SUMMARY: These large prospective patient cohorts, established and followed up by the CPDPC, provide a unique resource to improve the care of patients of all ages with pancreatitis, and to allow earlier diagnosis of pancreatic cancer.

ACG Clinical Guideline: Chronic Pancreatitis.

Chronic pancreatitis (CP) is historically defined as an irreversible inflammatory condition of the pancreas leading to varying degrees of exocrine and endocrine dysfunction. Recently however, the paradigm for the diagnosis has changed in that it breaks with the traditional clinicopathologic-based definition of disease, focusing instead on diagnosing the underlying pathologic process early in the disease course and managing the syndrome more holistically to change the natural course of disease and minimize adverse disease effects. Currently, the most accepted mechanistically derived definition of CP is a pathologic fibroinflammatory syndrome of the pancreas in individuals with genetic, environmental, and/or other risk factors who develop persistent pathologic responses to parenchymal injury or stress. The most common symptom of CP is abdominal pain, with other symptoms such as exocrine pancreatic insufficiency and diabetes developing at highly variable rates. CP is most commonly caused by toxins such as alcohol or tobacco use, genetic polymorphisms, and recurrent attacks of acute pancreatitis, although no history of acute pancreatitis is seen in many patients. Diagnosis is made usually on cross-sectional imaging, with modalities such as endoscopic ultrasonography and pancreatic function tests playing a secondary role. Total pancreatectomy represents the only known cure for CP, although difficulty in patient selection and the complications inherent to this intervention make it usually an unattractive option. This guideline will provide an evidence-based practical approach to the diagnosis and management of CP for the general gastroenterologist.

International Consensus Guidelines for Risk Factors in Chronic Pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club.

BACKGROUND: Chronic pancreatitis (CP) is a complex inflammatory disease with remarkably impaired quality of life and permanent damage of the pancreas. This paper is part of the international consensus guidelines on CP and presents the consensus on factors elevating the risk for CP. METHODS: An international working group with 20 experts on CP from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated 14 statements generated from evidence on four questions deemed to be the most clinically relevant in CP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available per statement. To determine the level of agreement, the working group voted on the 14 statements for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. RESULTS: Strong consensus and agreement were obtained for the following statements: Alcohol, smoking, and certain genetic alterations are risk factors for CP. Past history, family history, onset of symptoms, and life-style factors including alcohol intake and smoking history should be determined. Alcohol consumption dose-dependently elevates the risk of CP up to 4-fold. Ever smokers, even smoking less than a pack of cigarettes per day, have an increased risk for CP, as compared to never smokers. CONCLUSIONS: Both genetic and environmental factors can markedly elevate the risk for CP. Therefore, health-promoting lifestyle education and in certain cases genetic counselling should be employed to reduce the incidence of CP.

International consensus guidelines on surveillance for pancreatic cancer in chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club.

BACKGROUND: Patients with chronic pancreatitis (CP) have an increased risk of pancreatic cancer. We present the international consensus guidelines for surveillance of pancreatic cancer in CP. METHODS: The international group evaluated 10 statements generated from evidence on 5 questions relating to pancreatic cancer in CP. The GRADE approach was used to evaluate the level of evidence available per statement. The working group voted on each statement for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. RESULTS: In the following domains there was strong consensus: (1) the risk of pancreatic cancer in affected individuals with hereditary pancreatitis due to inherited PRSS1 mutations is high enough to justify surveillance; (2) the risk of pancreatic cancer in patients with CP associated with SPINK1 p. N34S is not high enough to justify surveillance; (3) surveillance should be undertaken in pancreatic specialist centers; (4) surveillance should only be introduced after the age of 40 years and stopped when the patient would no longer be suitable for surgical intervention. All patients with CP should be advised to lead a healthy lifestyle aimed at avoiding risk factors for progression of CP and pancreatic cancer. There was only moderate or weak agreement on the best methods of screening and surveillance in other types of environmental, familial and genetic forms of CP. CONCLUSIONS: Patients with inherited PRSS1 mutations should undergo surveillance for pancreatic cancer, but the best methods for cancer detection need further investigation.

Effect of referral pattern and histopathology grade on surgery for nonmalignant colorectal polyps.

BACKGROUND AND AIMS: The incidence of surgery for nonmalignant colorectal polyps is rising. The aims of this study were to evaluate referral patterns to surgery for nonmalignant polyps, to compare outcomes between surgery and endoscopic resection (ER), and to identify factors associated with surgery in a university-based, tertiary care center. METHODS: Patients referred to colorectal surgery (CRS) for nonmalignant colorectal polyps between 2014 and 2019 were selected from the institution's integrated data repository. Clinical characteristics were obtained through chart review. Multivariate analysis was performed to identify factors associated with surgery for nonmalignant polyps. RESULTS: Six hundred sixty-four patients with colorectal lesions were referred to CRS, of which 315 were for nonmalignant polyps. Most referrals (69%) came from gastroenterologists. Of the 315 cases, 136 underwent surgery and 117 were referred for attempt at ER. Complete ER was achieved in 87.2% (n = 102), with polyp recurrence in 27.2% at a median of 14 months (range, 0-72). When compared with surgery, ER was associated with a lower hospitalization rate (22.2% vs 95.6%; P < .0001), shorter hospital stay (mean, .5 ± .9 vs 2.23 ± 1 days; P < .0001), and fewer adverse events (5.9% vs 22.8%; P = .0002). Intramucosal adenocarcinoma on baseline pathology (odds ratio, 5.7; 95% confidence interval, 1.2-28.2) and referrals by academic gastroenterologists (odds ratio, 2.5; 95% confidence interval, 1.11-5.72) were associated with a higher likelihood of surgery on multivariate analysis. CONCLUSIONS: Gastroenterologists commonly refer nonmalignant colorectal polyps to surgery, even though ER is effective and associated with lower morbidity. Both referrals from academic gastroenterologists and baseline pathology of intramucosal adenocarcinoma were factors associated with surgery. All colorectal polyps should be evaluated in a multidisciplinary approach to identify lesions suitable for ER before embarking in surgery.

Period prevalence of chronic pancreatitis diagnosis from 2001-2013 in the commercially insured population of the United States.

BACKGROUND: Prevalence estimates of chronic pancreatitis (CP) in the US are scarce. We aimed to determine the prevalence of CP in the commercially insured population of the US. METHODS: We analyzed the IQVIA Legacy PharMetrics database to calculate the period prevalence of CP from 2001 to 2013 among individuals with ≥1 year of enrollment. CP was defined as ≥1 healthcare contacts associated with a non-ancillary claim for a primary diagnosis of CP (ICD-9-CM 577.1). Prevalence estimates were age- and sex- adjusted to the 2010 US population. Sensitivity analysis was performed by using more stringent criteria: a) 1 claim of CP + [≥1 claims of acute pancreatitis (AP), CP or pancreatic cyst/pseudocyst]; b) 1 claim of CP + [≥1 claims for AP, CP or pancreatic cyst/pseudocyst in ≥3 months before or after the index CP claim]; c) ≥2 claims for CP; and d) ≥2 claims for CP separated by ≥ 6 months. RESULTS: Of 48.67 million eligible enrollees, 37,061 received the diagnosis of CP (mean age, 51.2 ±â€¯15.2 years; 49% male). The age- and sex- adjusted period prevalence of CP per 100,000 was 73.4 (95% CI, 72.6-74.1), 98.7 (95% CI, 97.7-99.7) for adults and 8.3 (95% CI, 7.8-8.8) for children. Prevalence of CP was slightly higher in males (sex ratio, 1.05) and highest in the age group of 46-55 years (135/100,000). On sensitivity analysis, the prevalence of CP per 100,000 decreased to 60.2, 39.7, 38.8, and 18.8 with each of the alternative definitions. CONCLUSION: Prevalence estimates reported in our study provide an insight into the population burden of CP in the US.

A phase III, multicenter, prospective, single-blinded, noninferiority, randomized controlled trial on the performance of a novel esophageal stent with an antireflux valve (with video).

BACKGROUND AND AIMS: Self-expanding metal stents (SEMSs) when deployed across the gastroesophageal junction (GEJ) can lead to reflux with risks of aspiration. A SEMS with a tricuspid antireflux valve (SEMS-V) was designed to address this issue. The aim of this study was to evaluate the efficacy and safety of this stent. METHODS: A phase III, multicenter, prospective, noninferiority, randomized controlled trial was conducted on patients with malignant dysphagia requiring SEMSs to be placed across the GEJ. Patients were randomized to receive SEMSs with no valve (SEMS-NV) or SEMS-V. Postdeployment dysphagia score at 2 weeks and Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) questionnaire score at 4 weeks were measured. Patients were followed for 24 weeks. RESULTS: Sixty patients were randomized (SEMS-NV: 30 patients, mean age 67 ± 13 years; SEMS-V: 30 patients, mean age 65 ± 12 years). Baseline dysphagia scores (SEMS-NV, 2.5 ± .8; SEMS-V, 2.5 ± .8) and GERD-HRQL scores (SEMS-NV, 11.1 ± 8.2; SEMS-V, 12.8 ± 8.3) were similar. All SEMSs were successfully deployed. A similar proportion of patients in both arms improved from advanced dysphagia to moderate to no dysphagia (SEMS-NV, 71%; SEMS-V, 74%; 95% confidence interval, 1.93 [-17.8 to 21.7]). The dysphagia scores were also similar across all follow-up time points. Mean GERD-HRQL scores improved by 7.4 ± 10.2 points in the SEMS-V arm and by 5.2 ± 8.3 in the SEMS-NV group (P = .96). The GERD-HRQL scores were similar across all follow-up time points. Aspiration pneumonia occurred in 3.3% in the SEMS-NV arm and 6.9% in the SEMS-V arm (P = .61). Migration rates were similar (SEMS-NV, 33%; SEMS-V, 48%; P = .29). Two SEMS-V spontaneously fractured. There was no perforation, food impaction, or stent-related death in either group. CONCLUSIONS: The SEMS-V was equally effective in relieving dysphagia as compared with the SEMS-NV. Presence of the valve did not increase the risks of adverse events. GERD symptom scores were similar between the 2 stents, implying either that the valve was not effective or that all patients on proton pump inhibitors could have masked the symptoms of GERD. Studies with objective evaluations such as fluoroscopy and/or pH/impedance are recommended. (Clinical trial registration number: NCT02159898.).

Survey Study on the Practice Patterns of the Evaluation and Management of Incidental Pancreatic Cysts.

BACKGROUND AND AIMS: Various gastrointestinal societies have released guidelines on the evaluation of asymptomatic pancreatic cysts (PCs). These guidelines differ on several aspects, which create a conundrum for clinicians. The aim of this study was to evaluate preferences and practice patterns in the management of incidental PCs in light of these societal recommendations. METHODS: An electronic survey distributed to members of the American Society for Gastrointestinal Endoscopy (ASGE). Main outcomes included practice setting (academic vs. community), preferences for evaluation, management, and surveillance strategies for PCs. RESULTS: A total of 172 subjects completed the study (52% academic-based endoscopists). Eighty-six (50%) and 138 (80%) of the participants responded that they would recommend EUS surveillance of incidental PCs measuring less than 2 cm and 3 cm, respectively. Nearly half of the endosonographers (42.5% community and 44% academic; p = 1.0) would routinely perform FNA on PCs without any high-risk features. More academic-based endoscopists (57% academic vs. 32% community; p = 0.001) would continue incidental PC surveillance indefinitely. CONCLUSIONS: There is significant variability in the approach of incidental PCs among clinicians, with practice patterns often diverging from the various GI societal guideline recommendations. Most survey respondents would routinely recommend EUS-FNA and indefinite surveillance for incidental PCs without high-risk features. The indiscriminate use of EUS-FNA and indefinite surveillance of all incidental PCs is not cost-effective, exposes the patient to unnecessary testing, and can further perpetuate diagnostic uncertainty. Well-designed studies are needed to improve our diagnostic and risk stratification accuracy in order to formulate a consensus on the management of these incidental PCs.

Chronic pancreatitis.

PURPOSE OF REVIEW: Summarize key clinical advances in chronic pancreatitis reported in 2016. RECENT FINDINGS: Early diagnosis of chronic pancreatitis remains elusive. Recent studies suggest that endoscopic ultrasound may be less accurate than previously thought and new MRI techniques may be helpful. Genetic predisposition may independently affect the clinical course of chronic pancreatitis and the risk for pancreatic cancer. Cigarette smoking may have a greater negative impact on chronic pancreatitis than previously thought and moderate alcohol consumption may be protective. A multidisciplinary approach is necessary for the treatment of type 3 diabetes and nutritional deficiencies in chronic pancreatitis. Although endoscopic therapy remains a reasonable first-line option in treating chronic pancreatitis and its complications, early surgical intervention may be indicated for pain in select patients. SUMMARY: Newer endoscopic ultrasound and MRI techniques are being evaluated to help with the early diagnosis of chronic pancreatitis. Both genetic predisposition and cigarette smoking are increasingly recognized as having a major impact in the course of the disease and the risk for pancreatic cancer. Endoscopic therapy is well tolerated and effective for the treatment of chronic pancreatitis and its complications although an early surgical approach for pain may be associated with improved clinical outcomes.

Impact of Endotracheal Intubation on Interventional Endoscopy Unit Efficiency Metrics at a Tertiary Academic Medical Center.

OBJECTIVES: Measures for evaluating interventional endoscopy unit efficiency have not been adequately validated, especially in reference to the involvement of anesthesia services for endoscopy. Primary aim was to compare process measures/metrics of interventional endoscopy unit efficiency between intubated and non-intubated patients. Secondary aim was to assess variables associated with the need for endotracheal intubation. METHODS: The prospectively collected endoscopy unit metrics database at UF Health was reviewed for procedures performed in the interventional endoscopy unit for 6 months. Parameters included hospital-mandated metrics available from the database. RESULTS: A total of 1,421 patients underwent 1,635 interventional endoscopic procedures and 271/1,421 patients (19.1%) were intubated. There was no significant difference between intubated and non-intubated cohorts with respect to age, gender, BMI, ASA Score, Mallampati Score, or the Charlson Comorbidity Index. Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) were more frequently intubated than those undergoing non-ERCP procedures (41.3 vs. 12.4%, P<0.0001). Inpatients comprised 48.3% of all intubated patients, whereas only 29.2% of non-intubated patients were inpatients (P<0.0001). Most patients (159/271, 58.7%) were intubated per anesthesiologist preference. All process efficiency metrics were significantly prolonged in the intubated compared with the non-intubated patient cohort, except the time interval between successive procedures. Multivariate analysis revealed that patients with an anesthesiologist who had performed a greater number of total endoscopic sedations were less likely to be intubated than patients with an anesthesiologist who had performed fewer total procedures (P=0.0066). CONCLUSIONS: Endotracheal intubation negatively impacts efficiency metrics in an interventional endoscopy unit. Careful assessment for the need for intubation should be emphasized.