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Recurrent acute pancreatitis and chronic pancreatitis represent high morbidity diseases, which are frequently associated with chronic abdominal pain, pancreatic insufficiencies, and reduced quality of life. Currently, there are no therapies to reverse or delay disease progression, and clinical trials are needed to investigate potential interventions that would address this important gap. This conference report provides details regarding information shared during a National Institute of Diabetes and Digestive and Kidney Diseases-sponsored workshop on Clinical Trials in Pancreatitis that sought to clearly delineate the current gaps and opportunities related to the design and conduct of patient-focused trials in recurrent acute pancreatitis and chronic pancreatitis. Key stakeholders including representatives from patient advocacy organizations, physician investigators (including clinical trialists), the US Food and Drug Administration, and the National Institutes of Health convened to discuss challenges and opportunities with particular emphasis on lessons learned from trials in participants with other painful conditions, as well as the value of incorporating the patient perspective throughout all stages of trials.

OBJECTIVE Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP. RESEARCH DESIGN AND METHODS This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was evaluated by cross validation. Exploratory analyses were stratified according to the timing of development of diabetes relative to the diagnosis of pancreatitis. RESULTS Independent correlates of diabetes in CP included risk factors for type 2 diabetes (older age, overweight/obese status, male sex, non-White race, tobacco use) as well as pancreatic disease–related factors (history of acute pancreatitis complications, nonalcoholic etiology of CP, exocrine pancreatic dysfunction, pancreatic calcification, pancreatic atrophy) (AUROC 0.745). Type 2 diabetes risk factors were predominant for diabetes occurring before pancreatitis, and pancreatic disease–related factors were predominant for diabetes occurring after pancreatitis. CONCLUSIONS Multiple factors are associated with diabetes in CP, including canonical risk factors for type 2 diabetes and features associated with pancreatitis severity. This study lays the groundwork for the future development of models integrating clinical and nonclinical data to identify patients with CP at risk for diabetes and identifies modifiable risk factors (obesity, smoking) on which to focus for diabetes prevention.

Recruitment and retention of patients with acute pancreatitis (AP) in clinical studies can be challenging. While some obstacles are similar to other clinical conditions, some are unique to AP. Identifying potential barriers early and developing targeted solutions can help optimize recruitment and retention in AP studies. Such preemptive and detailed planning can help prospective, longitudinal studies focusing on exocrine and endocrine complications of AP in accurately measuring outcomes. This manuscript highlights the challenges in recruitment and retention strategies in AP studies and reviews available resources to create opportunities to address them. We describe the multifaceted approach used by the Recruitment and Retention Committee of the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC), which builds upon earlier experiences to develop a recruitment and retention plan for the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) study.

OBJECTIVES: The metabolic abnormalities that lead to diabetes mellitus (DM) following an episode of acute pancreatitis (AP) have not been extensively studied. This manuscript describes the objectives, hypotheses, and methods of mechanistic studies of glucose metabolism that comprise secondary outcomes of the Diabetes RElated to Acute pancreatitis and its Mechanisms (DREAM) Study. METHODS: Three months after an index episode of AP, participants without pre-existing DM will undergo baseline testing with an oral glucose tolerance test. Participants will be followed longitudinally in three sub-cohorts with distinct metabolic tests. In the first and largest subcohort, oral glucose tolerance tests will be repeated 12 months after AP and annually to assess changes in β-cell function, insulin secretion, and insulin sensitivity. In the second, mixed meal tolerance tests will be performed at 3 and 12 months, then annually, and following incident DM to assess incretin and pancreatic polypeptide responses. In the third, frequently-sampled intravenous glucose tolerance tests will be performed at 3 months and 12 months to assess the first-phase insulin response and more precisely measure β-cell function and insulin sensitivity. CONCLUSIONS: The DREAM study will comprehensively assess the metabolic and endocrine changes that precede and lead to the development of DM after AP.

Acute pancreatitis (AP) is a disease characterized by an acute inflammatory phase followed by a convalescent phase. Diabetes mellitus (DM) was historically felt to be a transient phenomenon related to acute inflammation; however, it is increasingly recognized as an important late and chronic complication. There are several challenges that have prevented precisely determining the incidence rate of DM following AP and understanding the underlying mechanisms. The Diabetes RElated to Acute Pancreatitis and its Mechanisms (DREAM) Study is a prospective cohort study designed to address these and other knowledge gaps to provide the evidence needed to screen for, prevent, and treat DM following AP. In the following article, we summarize literature regarding the epidemiology of DM following AP, and provide the rationale and an overview of the DREAM study.

PURPOSE OF REVIEW: Diabetes secondary to pancreatic diseases (i.e., acute pancreatitis, chronic pancreatitis, and pancreatic cancer) is increasingly studied, but remains challenging to distinguish from type 2 diabetes (T2DM). We review the clinical significance and potential biomarkers that may help differentiate these types of diabetes. RECENT FINDINGS: Recent studies have identified several complications (including non-vascular) that occur more frequently in patients with diabetes secondary to acute and chronic pancreatitis than T2DM, and biomarkers to differentiate the two types of diabetes. There have been advances that may enable the enrichment of a population of adults with new onset diabetes to potentially screen for occult pancreatic cancer, but efforts are needed to identify and validate promising diagnostic biomarkers. SUMMARY: High-quality studies are needed to more precisely understand the risk factors and natural course of diabetes secondary to pancreatic diseases. Mechanistic and interventional studies are awaited to provide insights that will distinguish diabetes secondary to pancreatic diseases and refine the management of hyperglycemia in this patient population.

PURPOSE OF REVIEW: The purpose of this review is to delineate risk factors for the development of diabetes in patients with chronic pancreatitis. The natural history including progression to diabetes and complications that develop once diabetes occurs in chronic pancreatitis is also reviewed. RECENT FINDINGS: Studies have found that predictors of diabetes in chronic pancreatitis include both risk factors for type 2 diabetes (e.g., obesity, genetic variants) as well as pancreas-specific factors (e.g., pancreatic calcification, exocrine insufficiency). Rates of diabetes in chronic pancreatitis are strongly related to the duration of chronic pancreatitis, reflecting progressive dysfunction and damage to the insulin-secreting beta-cells. Patients with diabetes and chronic pancreatitis experience an excess burden of complications, including higher all-cause and cancer-related mortality. SUMMARY: The high incidence and significant impact of diabetes on the morbidity and mortality of patients with chronic pancreatitis highlights the urgent need for clinically applicable models to predict diabetes in those with chronic pancreatitis, allowing efforts for targeted interventions to prevent diabetes. Research being carried out in the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) holds promise to fulfill these goals.

Purpose of review Diseases of the pancreas are a broad spectrum of conditions resulting from metabolic, inflammatory, and neoplastic processes (pancreatitis, pancreatogenic diabetes, and pancreatic cancers). Pancreatic diseases cause significant morbidity, mortality, and cost. Recent findings Research progress in diseases of the exocrine pancreas (chronic pancreatitis [CP], pancreatogenic diabetes mellitus, and pancreatic cancer) has been hampered by the disorders' heterogeneity, the limitations of previous small cross-sectional studies, the inability to safely obtain pancreatic tissue for study, and the lack of structured epidemiology tools, genetic testing, and biomarker development. Summary Given the increasing incidence and prevalence of CP and its complications, high mortality rate, and associated healthcare cost, the National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute funded the Consortium for the study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC) to identify research gaps and foster multidisciplinary collaborations to better diagnose, characterize and manage CP and its sequelae and to understand the diabetes/pancreatic cancer association.The studies undertaken by the CPDPC are described in other articles in this journal's issue.

To determine if quantitative MRI techniques can be helpful to evaluate chronic pancreatitis (CP) in a setting of multi-institutional study.This study included a subgroup of participants (n = 101) enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study (NCT03099850) from February 2019 to May 2021. MRI was performed on 1.5 T using Siemens and GE scanners at seven clinical centers across the USA. Quantitative MRI parameters of the pancreas included T1 relaxation time, extracellular volume (ECV) fraction, apparent diffusion coefficient (ADC), and fat signal fraction. We report the diagnostic performance and mean values within the control (n = 50) and CP (n = 51) groups. The T1, ECV and fat signal fraction were combined to generate the quantitative MRI score (Q-MRI).There was significantly higher T1 relaxation time; mean 669 ms (± 171) vs. 593 ms (± 82) (p = 0.006), ECV fraction; 40.2% (± 14.7) vs. 30.3% (± 11.9) (p 0.001), and pancreatic fat signal fraction; 12.2% (± 5.5) vs. 8.2% (± 4.4) (p 0.001) in the CP group compared to controls. The ADC was similar between groups (p = 0.45). The AUCs for the T1, ECV, and pancreatic fat signal fraction were 0.62, 0.72, and 0.73, respectively. The composite Q-MRI score improved the diagnostic performance (cross-validated AUC: 0.76).Quantitative MR parameters evaluating the pancreatic parenchyma (T1, ECV fraction, and fat signal fraction) are helpful in the diagnosis of CP. A Q-MRI score that combines these three MR parameters improves diagnostic performance. Further studies are warranted with larger study populations including patients with acute and recurrent acute pancreatitis and longitudinal follow-ups.

Our purpose was to validate the T1 SIR (T1 score) as an imaging biomarker for the staging of CP in a large, multi-institutional, prospective study.The prospective study population included 820 participants enrolled in the PROCEED study from nine clinical centers between June 2017 and December 2021. A radiologist at each institution used a standardized method to measure the T1 signal intensity of the pancreas and the reference organs (spleen, paraspinal muscle, liver), which was used to derive respective T1 scores. Participants were stratified according to the seven mechanistic stages of chronic pancreatitis (MSCP 0-6) based on their clinical history, MRCP, and CT findings.The mean pancreas-to-spleen T1 score was 1.30 in participants with chronic abdominal pain, 1.22 in those with acute or recurrent acute pancreatitis, and 1.03 in definite CP. After adjusting for covariates, we observed a linear, progressive decline in the pancreas-to-spleen T1 score with increasing MSCP from 0 to 6. The mean pancreas-to-spleen T1 scores were 1.34 (MSCP 0), 1.27 (MSCP 1), 1.21 (MSCP 2), 1.16 (MSCP 3), 1.18 (MSCP 4), 1.12 (MSCP 5), and 1.05 (MSCP 6) (p 0.0001). The pancreas-to-liver and pancreas-to-muscle T1 scores showed less linear trends and wider confidence intervals.The T1 score calculated by SIR of the pancreas-to-spleen shows a negative linear correlation with the progression of chronic pancreatitis. It holds promise as a practical imaging biomarker in evaluating disease severity in clinical research and practice.

Objective This exploratory study seeks to identify distinct circulating immune signatures among patients having recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic adenocarcinoma (PDAC). Methods A retrospective analysis of human serum samples from collaborating institutions of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) was performed. Samples came from the North American Pancreatitis Studies 2 (NAPS2) cohort and the Pancreatic Adenocarcinoma Gene Environment Risk Study (PAGER) and were analyzed using a 62-plex Luminex assay in a blinded fashion. Group and pairwise comparisons were performed to identify unique immune signature panels and to calculate diagnostic utility using area under the curve analysis. Results A total of 179 patients’ samples were included: 41 controls, 40 CP, 78 PDAC and 20 RAP patients, of which 20 controls, 20 CP, and 58 PDAC patients had diabetes mellitus (DM). A unique immune signature panel could discriminate RAP, CP, and PDAC from controls with an AUC range from 0.77 to 0.86 (95% CI range: 0.64–0.94), RAP from CP, and CP from PDAC with an AUC of 0.77 (95% CI 0.64–0.90) and 0.76 (95% CI 0.67–0.86), respectively. Furthermore, an immune signature panel could also discriminate PDAC-DM from DM controls with an AUC of 0.96 (95% CI: 0.93–1.00) Conclusion This study identifies unique immune analytes that may serve as novel diagnostic and predictive non-invasive biomarkers of RAP, CP, and PDAC. Further validation is warranted in prospective cohorts as developed by the CPDPC.

One hundred years have passed since the discovery of insulin—an achievement that transformed diabetes from a fatal illness into a manageable chronic condition. The decades since that momentous achievement have brought ever more rapid innovation and advancement in diabetes research and clinical care. To celebrate the important work of the past century and help to chart a course for its continuation into the next, the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases recently held a joint international symposium, bringing together a cohort of researchers with diverse interests and backgrounds from both countries and beyond to discuss their collective quest to better understand the heterogeneity of diabetes and thus gain insights to inform new directions in diabetes treatment and prevention. This article summarizes the proceedings of that symposium, which spanned cutting-edge research into various aspects of islet biology, the heterogeneity of diabetic phenotypes, and the current state of and future prospects for precision medicine in diabetes.

Recurrent acute pancreatitis (RAP) is a complex clinical syndrome with significant morbidity, unpredictable outcomes, and limited treatment options. The National Institute of Diabetes and Digestive and Kidney Disease sponsored a workshop on July 25, 2018, in Pittsburgh, Pennsylvania, to address research gaps impeding development of effective therapies for pancreatitis. The RAP working group identified challenges to clinical progress using existing definitions, risk assessment, diagnostic and severity criteria, disease trajectories, outcomes, and research methods. Recurrent acute pancreatitis includes all the risk of acute pancreatitis and often progresses to chronic pancreatitis with variable complications of chronic pain, exocrine insufficiency, diabetes, and pancreatic cancer. However, the great variability among individuals with RAP requires better precision in defining the risks, individual episodes, as well as their frequency, pathogenic pathways, and specific outcome measures for each of the systems affected by pancreatic inflammation. Because of disease complexity, few patients are similar enough for traditional studies and methods to conduct clinical trials with small sample sizes are required. The need for genetic testing, biomarker development, and better imaging methods was highlighted. Adaptive and N-of-one study designs, better endpoints, and outcome measures including patient-reported outcomes should considered early in developing future therapeutic trial design and include all stakeholders.

A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities on drug development for pancreatitis. This conference was held on July 25, 2018, and structured into 3 working groups (WG): acute pancreatitis (AP) WG, recurrent AP WG, and chronic pancreatitis WG. This article reports the outcome of the work accomplished by the AP WG to provide the natural history, epidemiology, and current management of AP; inform about the role of preclinical models in therapy selection; and discuss clinical trial designs with clinical and patient-reported outcomes to test new therapies.

The lack of effective therapeutic agents specifically tailored for chronic pancreatitis has hampered clinical care and negatively impacted patients’ lives. New mechanistic insights now point to novel therapies, which involve both recently developed and/or repurposed agents. This working group focused on two main outcomes for chronic pancreatitis: pain and progression of disease. The goal is to frame the essential aspects of trial design including patient-centered outcomes, proposed methods to measure the outcomes of pain and progression, and study design considerations for future trials to facilitate rapid drug development for patients with chronic pancreatitis.

Despite considerable research efforts, pancreatic cancer is associated with a dire prognosis and a 5-year survival rate of only 10%. Early symptoms of the disease are mostly nonspecific. The premise of improved survival through early detection is that more individuals will benefit from potentially curative treatment. Artificial intelligence (AI) methodology has emerged as a successful tool for risk stratification and identification in general health care. In response to the maturity of AI, Kenner Family Research Fund conducted the 2020 AI and Early Detection of Pancreatic Cancer Virtual Summit (www.pdac-virtualsummit.org) in conjunction with the American Pancreatic Association, with a focus on the potential of AI to advance early detection efforts in this disease. This comprehensive presummit article was prepared based on information provided by each of the interdisciplinary participants on one of the 5 following topics: Progress, Problems, and Prospects for Early Detection; AI and Machine Learning; AI and Pancreatic Cancer-Current Efforts; Collaborative Opportunities; and Moving Forward-Reflections from Government, Industry, and Advocacy. The outcome from the robust Summit conversations, to be presented in a future white paper, indicate that significant progress must be the result of strategic collaboration among investigators and institutions from multidisciplinary backgrounds, supported by committed funders.

Diabetes represents a group of diseases involving persistent hyperglycaemia. Exocrine disorders of the pancreas are increasingly recognised to cause or precede the onset of diabetes, which in this context is referred to as pancreatogenic or type 3c diabetes. Diabetes, as a sequela of acute pancreatitis, is observed across the spectrum of severity in acute pancreatitis and can be associated with other clinical complications. The pathophysiology of acute pancreatitis-related diabetes is poorly understood, and observations suggest that it is probably multifactorial. In this Review, we discuss the epidemiology, pathophysiology, and management considerations of diabetes following acute pancreatitis, and highlight knowledge gaps in this topic.

Simulation has become an integral part of physician education, and abundant evidence confirms that simulation-based education improves learners' skills and behaviors and is associated with improved patient outcomes. The resources required to implement simulation-based education, however, have led some stakeholders to question the overall value proposition of simulation-based education. This paper summarizes the information from a special panel on this topic and defines research priorities for the field. Future work should focus on both outcomes and costs, with robust measurement of resource investments, provider performance (in both simulation and real settings), patient outcomes, and impact on the health care organization. Increased attention to training practicing clinicians and health care teams is also essential. Clarifying the value proposition of simulation-based education will require a major national effort with funding from multiple sponsors and active engagement of a variety of stakeholders.

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer. The worldwide estimates of its incidence and mortality in the general population are eight cases per 100,000 person-years and seven deaths per 100,000 person-years, and they are significantly higher in the United States than in the rest of the world. The incidence of this disease in the United States is more than 50,000 new cases in 2017. Indeed, total deaths due to PDAC are projected to increase dramatically to become the second leading cause of cancer-related deaths before 2030. Considering the failure to date to efficiently treat existing PDAC, increased effort should be undertaken to prevent this disease. A better understanding of the risk factors leading to PDAC development is of utmost importance to identify and formulate preventive strategies. Large epidemiologic and cohort studies have identified risk factors for the development of PDAC, including obesity and type 2 diabetes mellitus. This review highlights the current knowledge of obesity and type 2 diabetes as risk factors for PDAC development and progression, their interplay and underlying mechanisms, and the relation to diet. Research gaps and opportunities to address this deadly disease are also outlined.

The relationships between diabetes and pancreatic ductal adenocarcinoma (PDAC) are complex. Longstanding type 2 diabetes (T2DM) is a risk factor for pancreatic cancer, but increasing epidemiological data point to PDAC as also a cause of diabetes due to unknown mechanisms. New-onset diabetes is of particular interest to the oncology community as the differentiation of new-onset diabetes caused by PDAC as distinct from T2DM may allow for earlier diagnosis of PDAC. To address these relationships and raise awareness of the relationships between PDAC and diabetes, a symposium entitled Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer was held at the American Diabetes Association’s 76th Scientific Sessions in June 2016. This article summarizes the data presented at that symposium, describing the current understanding of the interrelationships between diabetes, diabetes management, and pancreatic cancer, and identifies areas where additional research is needed.

A workshop on research gaps and opportunities for Precision Medicine in Pancreatic Disease was sponsored by the National Institute of Diabetes and Digestive Kidney Diseases on July 24, 2019, in Pittsburgh. The workshop included an overview lecture on precision medicine in cancer and 4 sessions: (1) general considerations for the application of bioinformatics and artificial intelligence; (2) omics, the combination of risk factors and biomarkers; (3) precision imaging; and (4) gaps, barriers, and needs to move from precision to personalized medicine for pancreatic disease. Current precision medicine approaches and tools were reviewed, and participants identified knowledge gaps and research needs that hinder bringing precision medicine to pancreatic diseases. Most critical were (a) multicenter efforts to collect large-scale patient data sets from multiple data streams in the context of environmental and social factors; (b) new information systems that can collect, annotate, and quantify data to inform disease mechanisms; (c) novel prospective clinical trial designs to test and improve therapies; and (d) a framework for measuring and assessing the value of proposed approaches to the health care system. With these advances, precision medicine can identify patients early in the course of their pancreatic disease and prevent progression to chronic or fatal illness.

Pain is the dominating symptom of chronic pancreatitis (CP) causing impairment of quality of life, decreased activity, unemployment and major healthcare costs.1 Opinions differ on the best strategy to treat CP-related pain. These differences are fuelled by the lack of a clear correlation between the severity of complaints and the presence and extent of morphological abnormalities, lack of a comprehensive pain assessment tools, deficiency in the knowledge about the natural course of CP and the presence of (changes in) both peripheral and central nervous system pain mechanisms. Analgesics are the cornerstone of pancreatic pain management, but when opioids are used, it may lead to dependency and opioid-induced hyperalgesia.2 When analgesic therapy fails, invasive treatments including endoscopic pancreatic duct clearance (with or without extracorporeal shock wave lithotripsy (ESWL)) or pancreatic duct stenting and surgery (resection and/or ductal decompression) are used. The rationale for invasive treatments is that reducing ductal pressure by restoring pancreatic juice flow and/or resecting an inflammatory pancreatic mass will result in pain relief. However, there is also a neuropathic basis for pain in most patients, for which invasive treatments may not be effective or even harmful. While there are many clinical studies that support invasive treatments, there is a paucity of high-quality randomised controlled trials (RCTs). As a result, the current guidelines for endoscopic and surgical treatments for painful CP are inconsistent and tend to reflect a specialty bias.3 For example, the German guidelines4 recommend surgery as the most effective treatment of pain, whereas the European Society of Gastrointestinal Endoscopy5 and the international evidence-based (HaPanEU) guidelines1 advice a ‘step-up approach’ incorporating both conservative, endoscopic and surgical treatment. These contradictions allow historic bias and a significant variation in clinical practice. Gut received a review article on the treatment of pain in CP that …

Interest in the use of simulation for acquiring, maintaining, and assessing skills in GI endoscopy has grown over the past decade, as evidenced by recent American Society for Gastrointestinal Endoscopy (ASGE) guidelines encouraging the use of endoscopy simulation training and its incorporation into training standards by a key accreditation organization. An EndoVators Summit, partially supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health, (NIH) was held at the ASGE Institute for Training and Technology from November 19 to 20, 2017. The summit brought together over 70 thought leaders in simulation research and simulator development and key decision makers from industry. Proceedings opened with a historical review of the role of simulation in medicine and an outline of priority areas related to the emerging role of simulation training within medicine broadly. Subsequent sessions addressed the summit's purposes: to review the current state of endoscopy simulation and the role it could play in endoscopic training, to define the role and value of simulators in the future of endoscopic training and to reach consensus regarding priority areas for simulation-related education and research and simulator development. This white paper provides an overview of the central points raised by presenters, synthesizes the discussions on the key issues under consideration, and outlines actionable items and/or areas of consensus reached by summit participants and society leadership pertinent to each session. The goal was to provide a working roadmap for the developers of simulators, the investigators who strive to define the optimal use of endoscopy-related simulation and assess its impact on educational outcomes and health care quality, and the educators who seek to enhance integration of simulation into training and practice.

A workshop on "The Interface of Pancreatic Cancer with Diabetes, Obesity, and Inflammation: Research Gaps and Opportunities" was held by the National Institute of Diabetes and Digestive and Kidney Diseases on October 12, 2017. The purpose of the workshop was to explore the relationship and possible mechanisms of the increased risk of pancreatic ductal adenocarcinoma (PDAC) related to diabetes, the role of altered intracellular energy metabolism in PDAC, the mechanisms and biomarkers of diabetes caused by PDAC, the mechanisms of the increased risk of PDAC associated with obesity, and the role of inflammatory events and mediators as contributing causes of the development of PDAC. Workshop faculty reviewed the state of the current knowledge in these areas and made recommendations for future research efforts. Further knowledge is needed to elucidate the basic mechanisms contributing to the role of hyperinsulinemia, hyperglycemia, adipokines, and acute and chronic inflammatory events on the development of PDAC.

Pancreatogenic diabetes mellitus is most commonly the result of chronic pancreatitis, but can also occur secondary to pancreatic cancer. The early identification of pancreatogenic diabetes and distinction from the more prevalent type 2 diabetes is clinically significant; however, currently there is no validated method to differentiate these diabetes subtypes. We describe a study, “Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: the DETECT study,” which seeks to address this knowledge gap. The DETECT study is a multicenter study that will examine differences in hormone and glucose excursions following a mixed meal test. The study will also create a biorepository that will be used to evaluate novel diagnostic biomarkers for differentiating these diabetes subtypes.

To determine which abdominal CT findings predict severe fibrosis and post-operative pain relief in chronic pancreatitis (CP). Pre-operative abdominal CTs of 66 patients (mean age 52 ± 12 years, 53 % males) with painful CP who underwent the Whipple procedure (n = 32), Frey procedure (n = 32) or pancreatic head biopsy (n = 2), between 1/2003-3/2014, were evaluated. CT was evaluated for parenchymal calcifications, intraductal calculi, main pancreatic duct dilation (>5 mm), main pancreatic duct stricture, and abnormal side branch(es). The surgical histopathology was graded for fibrosis. CT findings were evaluated as predictors of severe fibrosis and post-operative pain relief using regression and area under receiver operating curve (AUC) analysis. Thirty-eight (58 %) patients had severe fibrosis. Parenchymal calcification(s) were an independent predictor of severe fibrosis (p = 0.03), and post-operative pain relief over a mean follow-up of 1-year (p = 0.04). Presence of >10 parenchymal calcifications had higher predictive accuracy for severe fibrosis than 1-10 parenchymal calcification(s) (AUC 0.88 vs. 0.59, p = 0.003). The predictive accuracy of >10 versus 1-10 parenchymal calcifications increased after adjusting for all other CT findings (AUC 0.89 vs. 0.63, p = 0.01). Parenchymal calcification(s) independently predict severe fibrosis and are significantly associated with post-operative pain relief in CP. The presence of >10 parenchymal calcifications is a better predictor of severe fibrosis than 1-10 parenchymal calcification(s). • Parenchymal calcifications in chronic pancreatitis independently predict post-operative pain relief • Intraductal calculi and MPD dilation are not associated with post-operative pain relief • Better patient selection for pancreatic resection surgery in painful chronic pancreatitis

BACKGROUND: Bariatric surgery is the most effective treatment for the reduction of weight and resolution of type 2 diabetes mellitus (T2 DM). The objective of this study was to longitudinally assess hormonal and tissue responses after RYGB. METHODS: Eight patients (5 with T2 DM) were studied before and after RYGB. A standardized test meal (STM) was administered before and at 1, 3, 6, 9, 12, and 15 months. Separately, a 2-hour hyperinsulinemic-euglycemic clamp (E-clamp) and a 2-hour hyperglycemic clamp (H-clamp) were performed before and at 1, 3, 6, and 12 months. Glucagon-like peptide-1 (GLP-1) was infused during the last hour of the H-clamp. Body composition was assessed with DXA methodology. RESULTS: Enrollment body mass index was 49 ± 3 kg/m(2) (X ± SE). STM glucose and insulin responses were normalized by 3 and 6 months. GLP-1 level increased dramatically at 1, 3, and 6 months, normalizing by 12 and 15 months. Insulin sensitivity (M of E-clamp) increased progressively at 3–12 months as fat mass decreased. The insulin response to glucose alone fell progressively over 12 months but the glucose clearance/metabolism (M of H-clamp) did not change significantly until 12 months. In response to GLP-1 infusion, insulin levels fell progressively throughout the 12 months. CONCLUSION: The early hypersecretion of GLP-1 leads to hyperinsulinemia and early normalization of glucose levels. The GLP-1 response normalizes within 1 year after surgery. Enhanced peripheral tissue sensitivity to insulin starts at 3 months and is associated with fat mass loss. β-cell sensitivity improves at 12 months and after the loss of ≈ 33% of excess weight. There is a tightly controlled feedback loop between peripheral tissue sensitivity and β-cell and L-cell (GLP-1) responses. (Surg Obes Relat Dis 2014;10: 1028–1040.)

A workshop on ''Simulation Research in Gastrointestinal and Urologic Care: Challenges and Opportunities'' was held at the National Institutes of Health in June 2016. The purpose of the workshop was to examine the extent to which simulation approaches have been used by skilled proceduralists (not trainees) caring for patients with gastrointestinal and urologic diseases. The current status of research findings in the use and effectiveness of simulation applications was reviewed, and numerous knowledge gaps and research needs were identified by the faculty and the attendees. The paradigm of ''deliberate practice,'' rather than mere repetition, and the value of coaching by experts was stressed by those who have adopted simulation in music and sports. Models that are most useful for the adoption of simulation by expert clinicians have yet to be fully validated. Initial studies on the impact of simulation on safety and error reduction have demonstrated its value in the training domain, but the role of simulation as a strategy for increased procedural safety remains uncertain in the world of the expert practitioner. Although the basic requirements for experienced physicians to acquire new skills have been explored, the widespread availability of such resources is an unrealized goal, and there is a need for well-designed outcome studies to establish the role of simulation in improving the quality of health care.

This study aimed to compare severity of acute pancreatitis (AP) and mortality rates between transferred and nontransferred patients and to determine the factors that influence the decision to transfer.A retrospective analysis coding a statewide administrative database in Maryland was conducted. Severity was defined by presence of organ failure (OF), need for intensive care unit (ICU), mechanical ventilation (MV), or hemodialysis.There were 71,035 discharges for AP, with 1657 (2.3%) patient transfers. Transferred patients had more multisystem OF (5.6% vs 1.2%), need for ICU (22.8% vs 4.3%), MV (13.1% vs 1.4%), hemodialysis (4.2% vs 2.7%), and higher mortality (6.1% vs 1.1%) compared with nontransferred patients (P0.0001). After adjusting for disease severity, mortality was similar between the transferred patients and the nontransferred patients (OR, 1.37; 95% confidence interval, 0.96-1.97). Younger (OR, 0.99), African American (OR, 0.55), and uninsured (OR, 0.46) patients were less likely to be transferred, whereas patients with multisystem OF (OR, 3.5), need for ICU (OR, 2.3), or MV (OR, 2.1) were more likely to be transferred (P0.0001).Transferred patients with AP have more severe disease and higher overall mortality. Mortality is similar after adjusting for disease severity. Disease severity, insurance status, race, and age all influence the decision to transfer patients with AP.

Intensive insulin therapy for tight glycemic control in critically ill surgical patients has been shown to reduce mortality; however, intensive insulin therapy is associated with iatrogenic hypoglycemia and increased variability of blood glucose levels. The incretin glucagon-like peptide-1 (7-36) amide is both insulinotropic and insulinomimetic and has been suggested as an adjunct to improve glycemic control in critically ill patients. We hypothesized that the addition of continuous infusion of glucagon-like peptide-1 to intensive insulin therapy would result in better glucose control, reduced requirement of exogenous insulin administration, and fewer hypoglycemic events.Prospective, randomized, double-blind, placebo-controlled clinical trial.Surgical or burn ICU.Eighteen patients who required intensive insulin therapy.A 72-hour continuous infusion of either glucagon-like peptide-1 (1.5 pmol/kg/min) or normal saline plus intensive insulin therapy.The glucagon-like peptide-1 cohort (n = 9) and saline cohort (n = 9) were similar in age, Acute Physiology and Chronic Health Evaluation score, and history of diabetes. Blood glucose levels in the glucagon-like peptide-1 group were better controlled with much less variability. The coefficient of variation of blood glucose ranged from 7.2% to 30.4% in the glucagon-like peptide-1 group and from 19.8% to 56.8% in saline group. The mean blood glucose coefficient of variation for the glucagon-like peptide-1 and saline groups was 18.0% ± 2.7% and 30.3% ± 4.0% (p = 0.010), respectively. The 72-hour average insulin infusion rates were 3.37 ± 0.61 and 4.57 ± 1.18 U/hr (p = not significant). The incidents of hypoglycemia (≤ 2.78 mmol/L) in both groups were low (one in the glucagon-like peptide-1 group, three in the saline group).Glucagon-like peptide-1 (7-36) amide is a safe and efficacious form of adjunct therapy in patients with hyperglycemia in the surgical ICU setting. Improved stability of blood glucose is a favorable outcome, which enhances the safety of intensive insulin therapy. Larger studies of this potentially valuable therapy for glycemic control in the ICU are justified.

Description Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure used to treat severe complications of chronic pancreatitis or very high risk of pancreatic cancer while reducing the risk of severe diabetes mellitus. However, clear guidance on indications, contraindications, evaluation, timing, and follow-up are lacking. Methods A working group reviewed the medical, psychological, and surgical options and supporting literature related to TPIAT for a consensus meeting during PancreasFest . Results Five major areas requiring clinical evaluation and management were addressed: These included: 1) indications for TPIAT; 2) contraindications for TPIAT; 3) optimal timing of the procedure; 4) need for a multi-disciplinary team and the roles of the members; 5) life-long management issues following TPIAP including diabetes monitoring and nutrition evaluation. Conclusions TPIAT is an effective method of managing the disabling complications of chronic pancreatitis and risk of pancreatic cancer in very high risk patients. Careful evaluation and long-term management of candidate patients by qualified multidisciplinary teams is required. Multiple recommendations for further research were also identified.

The objectives of this study were to evaluate the severity of patients with acute pancreatitis (AP) on chronic pancreatitis (CP) and compare this to patients with AP without CP.The Maryland Health Services database was queried for all adult inpatient discharges with a primary diagnosis of AP from 1994 to 2010. Acute pancreatitis on CP and AP without CP were defined by the presence of the associated diagnosis code for CP. Severity was defined as organ failure, intensive care unit stay, or mortality.Acute pancreatitis on CP accounted for 13.7% of all AP discharges (9747/70,944). The proportion of AP-on-CP discharges doubled during the study period (8.8% to 17.6%; P0.0001). When compared with patients with AP without CP, AP-on-CP patients were younger, were more likely to be male and black, had higher rates of alcohol and drug abuse, and had less severe disease with lower rates of mortality, organ failure, need for mechanical ventilation, and intensive care unit stay. Among AP-on-CP patients, significant predictors of severity included advanced age, weight loss, and 2 or more comorbidities.Patients with AP on CP have less severe disease than do those with AP without CP. Weight loss, advanced age, and comorbidity increase the risk of severity in patients with AP on CP.

Our aim was to assess the impact of immediate preoperative laparoscopic warm-up using a simulator on intraoperative laparoscopic performance by gynecologic residents. Eligible laparoscopic cases performed for benign, gynecologic indications were randomized to be performed with or without immediate preoperative warm-up. Residents randomized to warm-up performed a brief set of standardized exercises on a laparoscopic trainer immediately before surgery. Intraoperative performance was scored using previously validated global rating scales. Assessment was made immediately after surgery by attending faculty who were blinded to the warm-up randomization. We randomized 237 residents to 47 minor laparoscopic cases (adnexal/ tubal surgery) and 44 to major laparoscopic cases (hysterectomy). Overall, attendings rated upper-level resident performances (postgraduate year [PGY-3, 4]) significantly higher on global rating scales than lower-level resident performances (PGY-1, 2). Residents who performed warm-up exercises prior to surgery were rated significantly higher on all subscales within each global rating scale, irrespective of the difficulty of the surgery. Most residents felt that performing warm-up exercises helped their intraoperative performances. Performing a brief warm-up exercise before a major or minor laparoscopic procedure significantly improved the intraoperative performance of residents irrespective of the difficulty of the case.

The association of diabetes and cancer has received increased attention as data have emerged to indicate that the type of diabetes treatment may influence the risk of cancer, and that the risk of cancer among diabetic individuals can be reduced by intervention. The association of diabetes and pancreatic cancer is particularly strong, but often misunderstood. Long-standing type 1 diabetes and type 2 diabetes increase the risk for this malignancy, but the cancer can also induce pancreatogenic, or type 3c, diabetes as well.This review covers the recent findings which help to clarify these relationships, and offers guidance for prevention, early detection, and treatment. Obesity and, separately, diabetes increase the risk of several common malignancies by about two-fold. This risk is reduced by successful treatments. Type 3c diabetes is more common than previously realized, and strategies to differentiate type 3c diabetes from type 2 diabetes, to identify those candidates who will benefit from screening studies, are discussed.The death rate because of pancreatic and other cancers can be reduced by an aggressive approach to reversing obesity and hyperinsulinemia, achieving good glycemic control in diabetic patients, and identifying at an early timepoint those patients with pancreatogenic diabetes.

Summary Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia. Type 2 diabetes, the most prevalent form, is characterised initially by impaired insulin sensitivity and subsequently by an inadequate compensatory insulin response. Diabetes can also develop as a direct consequence of other diseases, including diseases of the exocrine pancreas. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic or pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c diabetes. It is important to note that type 3c diabetes is not a single entity; it occurs because of a variety of exocrine pancreatic diseases with varying mechanisms of hyperglycaemia. The most commonly identified causes of type 3c diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma, haemochromatosis, cystic fibrosis, and previous pancreatic surgery. In this Review, we discuss the epidemiology, pathogenesis, and clinical relevance of type 3c diabetes secondary to chronic pancreatitis and pancreatic ductal adenocarcinoma, and highlight several important knowledge gaps.

Background Multiple factors influence mortality in Acute Pancreatitis (AP). Methods To evaluate the association of demographic, clinical, and hospital factors with the in-hospital mortality of AP using a population-based administrative database. The Maryland HSCRC database was queried for adult (≥18 years) admissions with primary diagnosis of AP between 1/94-12/10. Organ failure (OF), interventions, hospital characteristics and referral status were evaluated. Results There were 72,601 AP admissions across 48 hospitals in Maryland with 885 (1.2%) deaths. A total of 1657 (2.3%) were transfer patients, of whom 101 (6.1%) died. Multisystem OF was present in 1078 (1.5%), of whom 306 (28.4%) died. On univariable analysis, age, male gender, transfer status, comorbidity, OF, all interventions, and all hospital characteristics were significantly associated with mortality; however, only age, transfer status, OF, interventions, and large hospital size were significant in the adjusted analysis. Patients with commercial health insurance had significantly less mortality than those with other forms of insurance (OR 0.65, 95% CI: 0.52, 0.82, p = 0.0002). Conclusion OF is the strongest predictor of mortality in AP after adjusting for demographic, clinical, and hospital characteristics. Admission to HV or teaching hospital has no survival benefit in AP after adjusting for OF and transfer status.

Background/Aims: Pancreatogenic, or type 3c, diabetes (T3cDM) occurs due to inherited or acquired pancreatic disease or resection. Although similar to the more prevalent type 1 and type 2 diabetes, pancreatogenic diabetes has a unique pattern of hormonal and metabolic characteristics and a high incidence of pancreatic carcinoma in the majority of patients with T3cDM. Despite these differences, no guidelines for therapy have been described. Methods: Published studies on the prevalence, pathophysiology, and cancer associations of T3cDM were reviewed. The recent studies on the protective role and mechanism of metformin therapy as both an anti-diabetic and anti-neoplastic agent were reviewed, and studies on the cancer risk of other anti-diabetic drugs were surveyed. Results: T3cDM accounts for 5–10% of Western diabetic populations and is associated with mild to severe disease. Hepatic insulin resistance is characteristic of T3cDM and is caused by deficiencies of both insulin and pancreatic polypeptide. 75% of T3cDM is due to chronic pancreatitis, which carries a high risk for pancreatic carcinoma. Insulin and insulin secretagogue treatment increases the risk of malignancy, whereas metformin therapy reduces it. Pancreatic exocrine insufficiency associated with T3cDM contributes to nutritional deficiencies and the development of metabolic bone disease. Conclusions: Until consensus recommendations are reached, the glycemic treatment of T3cDM should avoid insulin and insulin secretagogues if possible. Metformin should be the first line of therapy, and continued if insulin treatment must be added for adequate glucose control. Pancreatic enzyme therapy should be added to prevent secondary nutritional and metabolic complications.

Hyperinsulinemic hypoglycemia with severe neuroglycopenia has been identified as a late complication of Roux-en-Y gastric bypass (RYGB) in a small number of patients. The rapid resolution of type 2 diabetes mellitus after RYGB is probably related to increased secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and patients with post-RYGB hypoglycemia demonstrate prolonged elevations of GIP and GLP-1 compared to non-hypoglycemic post-RYGB patients. Nesidioblastosis has been identified in some patients with post-RYGB hypoglycemia and is likely due to the trophic effects of GIP and GLP-1 on pancreatic islets. Treatment of hypoglycemia after RYGB should begin with strict dietary (low carbohydrate) alteration and may require a trial of diazoxide, octreotide, or calcium-channel antagonists, among other drugs. Surgical therapy should include consideration of a restrictive form of bariatric procedure, with or without reconstitution of gastrointestinal continuity. Partial or total pancreatic resection should be avoided.

Objective: To establish the current status of surgical therapy for chronic pancreatitis, recent published reports are examined in the context of the historical advances in the field. Background: The basis for decompression (drainage), denervation, and resection strategies for the treatment of pain caused by chronic pancreatitis is reviewed. These divergent approaches have finally coalesced as the head of the pancreas has become apparent as the nidus of chronic inflammation. Methods: The recent developments in surgical methods to treat the complications of chronic pancreatitis and the results of recent prospective randomized trials of operative approaches were reviewed to establish the current best practices. Results: Local resection of the pancreatic head, with or without duct drainage, and duodenum-preserving pancreatic head resection offer outcomes as effective as pancreaticoduodenectomy, with lowered morbidity and mortality. Local resection or excavation of the pancreatic head offers the advantage of lowest cost and morbidity and early prevention of postoperative diabetes. The late incidences of recurrent pain, diabetes, and exocrine insufficiency are equivalent for all 3 surgical approaches. Conclusions: Local resection of the pancreatic head appears to offer best outcomes and lowest risk for the management of the pain of chronic pancreatitis. (Ann Surg 2010;251: 18‐32)

In contrast to the benefits of intensive insulin therapy (IIT) in the surgical intensive care unit (SICU), its benefits in the burn ICU (BICU) remain unclear. Furthermore, IIT and tight glycemic control has received little attention in elderly ICU patients.We evaluated the normalization of blood glucose level with IIT in BICU and SICU patients. From October 2006 to July 2007, 970 patients were admitted to our BICU and our SICU. A total of 79 of these patients met criteria for initiation of IIT, 37 of who required IIT for at least 72 hours. Data were analyzed to determine if tight glycemic control (blood glucoseor =150 mg/dL by day 3) is associated with reduced morbidity and mortality.Tight control was better achieved in SICU patients (45%) than in BICU patients (33%). Daily insulin requirements were approximately 2-fold greater in SICU patients compared with BICU patients (P.05). Tight control in both SICU and BICU patients was associated with a decreased incidence of sepsis compared with poor glycemic control (10% vs 58% and 60% vs 70%, respectively) and a decreased mortality rate (0 vs 58% and 20% vs 50%; SICU vs BICU, respectively). The percentage of total body surface area burned in BICU patients was 10% and 45% in theor =150 and150 mg/dL groups. Mortality rate in the poor control group was10-fold greater than that of the tight control group; for patientsor =65 years of age, mortality was nearly double than that of patients65 years of age. The greatest mortality rate (62%) was seen in patients65 years of age with poor control.Tight control with IIT is associated with an increased survival rate in both BICU and SICU patients. Age is associated with survival, with patients older than 65 years of age having the greatest mortality rate.

Intensive insulin therapy (IIT) for glycemic control in critically ill patients has been shown to be beneficial. Continuous glucose monitoring systems (CGMSs) have been approved as an adjunct to complement standard glucose monitoring in type 2 diabetes mellitus. This study was designed to evaluate the accuracy of a real-time CGMS (DexCom STS) in the intensive care unit (ICU). We also evaluated its reliability and accuracy using a hyperinsulinemic-euglycemic and a hyperglycemic clamp study.Nineteen patients were enrolled in this 7-day study [13 = surgical intensive care unit (SICU), 6 = burn intensive care unit (BICU)]. The patients were on IIT for at least 2 h prior the subcutaneous sensor insertion. Mean age and body mass index for SICU and BICU patients were 60.3 +/- 3.7 and 64.5 +/- 6.2 years and 36.6 +/- 5.0 and 33.85 +/- 3.4 kg/m2, respectively. DexCom accuracy was analyzed separately for the JohnsonJohnson (JJ) calibration finger sticks, Roche Accucheck finger sticks, and the Hitachi 917 analyzer measurements on serum using Clarke error grid analysis and Bland-Altman analysis. In the clamp studies, 20 patients were enrolled, and the data were analyzed similarly.There were 1065 pairs of DexCom-Accucheck, 232 pairs of DexCom-JJ, and 84 pairs of DexCom-Hitachi in ICU patients. For DexCom-Accucheck, 68.26% of the pairs fell into zone A, 31.83% into zone B, and 0.75% into zone C. There were no values in zones D or E. From the 1102 matching DexCom-Beckman pairs in clamp studies, 42.29% were in zone A, 55.90% were in zone B, and 4.08% were in zone C.Despite the high percentage of measurements in zones A and B, underestimation of hypoglycemia by DexCom measurements makes it an unreliable device in the ICU setting.

Context: Glucagon-like peptide-1 (GLP-1) 7-36 amide, an insulinotropic hormone released from the intestinal L cells in response to nutrient ingestion, has been extensively reviewed with respect to β-cell function. However GLP-1 receptors are abundant in many other tissues. Thus, the function of GLP-1 is not limited to the islet cells, and it has regulatory actions on many other organs. Evidence Acquisition: A review of published, peer-reviewed medical literature (1987 to September 2008) on the extrapancreatic actions of GLP-1 was performed. Evidence Synthesis: The extrapancreatic actions of GLP-1 include inhibition of gastric emptying and gastric acid secretion, thereby fulfilling the definition of GLP-1 as an enterogastrone. Other important extrapancreatic actions of GLP-1 include a regulatory role in hepatic glucose production, the inhibition of pancreatic exocrine secretion, cardioprotective and cardiotropic effects, the regulation of appetite and satiety, and stimulation of afferent sensory nerves. The primary metabolite of GLP-1, GLP-1 (9-36) amide, or GLP-1m, is the truncated product of degradation by dipeptidyl peptidase-4. GLP-1m has insulinomimetic effects on hepatic glucose production and cardiac function. Exendin-4 present in the salivary gland of the reptile, Gila monster (Heloderma suspectum), is a high-affinity agonist for the mammalian GLP-1 receptor. It is resistant to degradation by dipeptidyl peptidase-4, and therefore has a prolonged half-life. Conclusion: GLP-1 and its metabolite have important extrapancreatic effects particularly with regard to the cardiovascular system and insulinomimetic effects with respect to glucose homeostasis. These effects may be particularly important in the obese state. GLP-1, GLP-1m, and exendin-4 therefore have potential therapeutic roles because of their diffuse extrapancreatic actions.

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC.

Post-operative pain relief in chronic pancreatitis (CP) is variable. Our objective was to determine clinical imaging or histopathologic predictor(s) of post-operative pain relief in CP patients undergoing the Whipple or Frey procedure. All patients who underwent a Whipple (n = 30) or Frey procedure (n = 30) for painful CP between January 2003 and September 2013 were evaluated. A toxic etiology was defined as a history of alcohol use and/or smoking. The pre-operative abdominal CT was evaluated for calcification(s) and main pancreatic duct (MPD) dilation (≥5 mm). The post-operative histopathology was evaluated for severe fibrosis. Clinical imaging and histopathologic features were evaluated as predictors of post-operative pain relief using univariable and multivariable regression analysis. A total of 60 patients (age 51.6 years, 53 % males) were included in our study, of whom 42 (70 %) reported post-operative pain relief over a mean follow-up of 1.1 years. There were 37 (62 %) patients with toxic etiology, 36 (60 %) each with calcification(s) and MPD dilation. A toxic etiology, calcifications, and severe fibrosis were associated with post-operative pain relief on univariable analysis (all p

Islet transplantation can improve glycemic control in patients with type 1 diabetes and reduce or eliminate the need for insulin. Glucagon-like peptide-1 (GLP-1) is an intestinal insulinotropic hormone that augments glucose induced insulin secretion, and has a trophic effect on beta-cells. We evaluated the effect of GLP-1 on insulin secretion after islet transplantation. Patients underwent hyperglycemic glucose clamp studies 1 month after their last transplant. GLP-1 was infused during the second hour of the hyperglycemic clamp. Results were compared to normal control subjects and patients with type 2 diabetes who underwent an identical hyperglycemic clamp. First phase insulin release was absent in patients, while second phase insulin was not significantly reduced (control: 118+/-29 pM; type 2 diabetes: 68+/-20 pM; transplant: 99+/-18 pM, p=ns for all). GLP-1 had a significant incretin effect on transplanted islets but the response was less than controls (control: 2108+/-344 pM; type 2 diabetes: 929+/-331 pM; transplant: 329+/-112 pM, p0.0001 control versus transplant). Islet transplant patients had no evidence of resistance to insulin mediated glucose disposal. We conclude that transplanted islets retain the ability to respond to GLP-1.

Endoscopic ultrasound (EUS) has been compared to intraoperative surgical palpation for diagnosis of vascular invasion by pancreatic cancer. This study compares EUS with vascular resection and histologic evidence of vascular invasion in resected pancreatic masses.All patients with solid pancreatic masses who underwent both preoperative EUS and surgery at 1 hospital over a 7 year period were identified. The relationship of pancreatic masses to adjacent vessels was prospectively assessed by EUS. EUS findings were compared to surgical and pathology gold standards. "Vascular adherence" was defined as tumor adherence requiring vascular resection during surgery, and "vascular invasion" as histologic invasion of vessel wall by tumor.30 of 68 patients were resectable. Among these 30, vascular adherence was present in 8, including 18% of patients with an intact echoplane between tumor and adjacent vessels at EUS, 29% of those with loss of echoplane alone, and 50% of those with additional EUS features of vascular involvement. Vascular invasion was present in 4, including 12% of patients with an intact echoplane, 0% of those with loss of echoplane alone, and 33% of those with additional EUS features. Sensitivity, specificity, PPV, and NPV of EUS were 63%, 64%, 43% and 80% for vascular adherence and 50% 58%, 28% and 82% for vascular invasion. NPV rose to 90% for vascular adherence if only the portal confluence vessels were considered.EUS has poor sensitivity, specificity, and positive predictive value for diagnosis of venous involvement by pancreatic cancer.