The roles of calcium and ATP in the physiology and pathology of the exocrine pancreas.

This review deals with the roles of calcium ions and ATP in the control of the normal functions of the different cell types in the exocrine pancreas as well as the roles of these molecules in the pathophysiology of acute pancreatitis. Repetitive rises in the local cytosolic calcium ion concentration in the apical part of the acinar cells not only activate exocytosis but also, via an increase in the intramitochondrial calcium ion concentration, stimulate the ATP formation that is needed to fuel the energy-requiring secretion process. However, intracellular calcium overload, resulting in a global sustained elevation of the cytosolic calcium ion concentration, has the opposite effect of decreasing mitochondrial ATP production, and this initiates processes that lead to necrosis. In the last few years it has become possible to image calcium signaling events simultaneously in acinar, stellate, and immune cells in intact lobules of the exocrine pancreas. This has disclosed processes by which these cells interact with each other, particularly in relation to the initiation and development of acute pancreatitis. By unraveling the molecular mechanisms underlying this disease, several promising therapeutic intervention sites have been identified. This provides hope that we may soon be able to effectively treat this often fatal disease.

Human stem cell models: lessons for pancreatic development and disease.

A comprehensive understanding of mechanisms that underlie the development and function of human cells requires human cell models. For the pancreatic lineage, protocols have been developed to differentiate human pluripotent stem cells (hPSCs) into pancreatic endocrine and exocrine cells through intermediates resembling in vivo development. In recent years, this differentiation system has been employed to decipher mechanisms of pancreatic development, congenital defects of the pancreas, as well as genetic forms of diabetes and exocrine diseases. In this review, we summarize recent insights gained from studies of pancreatic hPSC models. We discuss how genome-scale analyses of the differentiation system have helped elucidate roles of chromatin state, transcription factors, and noncoding RNAs in pancreatic development and how the analysis of cells with disease-relevant mutations has provided insight into the molecular underpinnings of genetically determined diseases of the pancreas.

Liver Transplantation in a Woman with Mahvash Disease.

Mahvash disease is an exceedingly rare genetic disorder of glucagon signaling characterized by hyperglucagonemia, hyperaminoacidemia, and pancreatic α-cell hyperplasia. Although there is no known definitive treatment, octreotide has been used to decrease systemic glucagon levels. We describe a woman who presented to our medical center after three episodes of small-volume hematemesis. She was found to have hyperglucagonemia and pancreatic hypertrophy with genetically confirmed Mahvash disease and also had evidence of portal hypertension (recurrent portosystemic encephalopathy and variceal hemorrhage) in the absence of cirrhosis. These findings established a diagnosis of portosinusoidal vascular disease, a presinusoidal type of portal hypertension previously known as noncirrhotic portal hypertension. Liver transplantation was followed by normalization of serum glucagon and ammonia levels, reversal of pancreatic hypertrophy, and resolution of recurrent encephalopathy and bleeding varices.

Overexpression of Pdx1, reduction of p53, or deletion of CHOP attenuates pancreas hypoplasia in mice with pancreas-specific O-GlcNAc transferase deletion.

Deletion of O-GlcNAc transferase (Ogt) in pancreatic epithelial progenitor cells results in pancreatic hypoplasia at birth, partly due to increased apoptosis during embryonic development. Constitutive loss of Ogt in ß-cells results in increased ER stress and apoptosis, and in the Ogt-deficient pancreas, transcriptomic data previously revealed both tumor suppressor protein p53 and pancreatic duodenal homeobox 1 (Pdx1), key cell survival proteins in the developing pancreas, as upstream regulators of differentially expressed genes. However, the specific roles of these genes in pancreatic hypoplasia are unclear. In this study, we explored the independent roles of p53, ER stress protein CHOP, and Pdx1 in pancreas development and their use in the functional rescue of pancreatic hypoplasia in the context of Ogt loss. Using in vivo genetic manipulation and morphometric analysis, we show that Ogt plays a key regulatory role in pancreas development. Heterozygous, but not homozygous, loss of pancreatic p53 afforded a partial rescue of ß-cell, α-cell, and exocrine cell masses, while whole body loss of CHOP afforded a partial rescue in pancreas weight and a full rescue in exocrine cell mass. However, neither was sufficient to fully mitigate pancreatic hypoplasia at birth in the Ogt-deficient pancreas. Furthermore, overexpression of Pdx1 in the pancreatic epithelium resulted in partial rescues in pancreas weight and ß-cell mass in the Ogt loss background. These findings highlight the requirement of Ogt in pancreas development by targeting multiple proteins such as transcription factor Pdx1 and p53 in the developing pancreas.

PancrESS - a meta-analysis resource for understanding cell-type specific expression in the human pancreas.

BACKGROUND: The human pancreas is composed of specialized cell types producing hormones and enzymes critical to human health. These specialized functions are the result of cell type-specific transcriptional programs which manifest in cell-specific gene expression. Understanding these programs is essential to developing therapies for pancreatic disorders. Transcription in the human pancreas has been widely studied by single-cell RNA technologies, however the diversity of protocols and analysis methods hinders their interpretability in the aggregate. RESULTS: In this work, we perform a meta-analysis of pancreatic single-cell RNA sequencing data. We present a database for reference transcriptome abundances and cell-type specificity metrics. This database facilitates the identification and definition of marker genes within the pancreas. Additionally, we introduce a versatile tool which is freely available as an R package, and should permit integration into existing workflows. Our tool accepts count data files generated by widely-used single-cell gene expression platforms in their original format, eliminating an additional pre-formatting step. Although we designed it to calculate expression specificity of pancreas cell types, our tool is agnostic to the biological source of count data, extending its applicability to other biological systems. CONCLUSIONS: Our findings enhance the current understanding of expression specificity within the pancreas, surpassing previous work in terms of scope and detail. Furthermore, our database and tool enable researchers to perform similar calculations in diverse biological systems, expanding the applicability of marker gene identification and facilitating comparative analyses.

Mechanisms of spinophilin-dependent pancreas dysregulation in obesity.

Spinophilin is an F-actin binding and protein phosphatase 1 (PP1) targeting protein that acts as a scaffold of PP1 to its substrates. Spinophilin knockout (Spino-/-) mice have decreased fat mass, increased lean mass, and improved glucose tolerance, with no difference in feeding behaviors. Although spinophilin is enriched in neurons, its roles in nonneuronal tissues, such as ß cells of the pancreatic islets, are unclear. We have corroborated and expanded upon previous studies to determine that Spino-/- mice have decreased weight gain and improved glucose tolerance in two different models of obesity. We have identified multiple putative spinophilin-interacting proteins isolated from intact pancreas and observed increased interactions of spinophilin with exocrine, ribosomal, and cytoskeletal protein classes that normally act to mediate peptide hormone production, processing, and/or release in Leprdb/db and/or high-fat diet-fed (HFF) models of obesity. In addition, we have found that spinophilin interacts with proteins from similar classes in isolated islets, suggesting a role for spinophilin in the pancreatic islet. Consistent with a pancreatic ß cell type-specific role for spinophilin, using our recently described conditional spinophilin knockout mice, we found that loss of spinophilin specifically in pancreatic ß cells improved glucose tolerance without impacting body weight in chow-fed mice. Our data further support the role of spinophilin in mediating pathophysiological changes in body weight and whole body metabolism associated with obesity. Our data provide the first evidence that pancreatic spinophilin protein interactions are modulated by obesity and that loss of spinophilin specifically in pancreatic ß cells impacts whole body glucose tolerance.NEW & NOTEWORTHY To our knowledge, these data are the first to demonstrate that obesity impacts spinophilin protein interactions in the pancreas and identify spinophilin specifically in pancreatic ß cells as a modulator of whole body glucose tolerance.

UBR7 functions with UBR5 in the Notch signaling pathway and is involved in a neurodevelopmental syndrome with epilepsy, ptosis, and hypothyroidism.

The ubiquitin-proteasome system facilitates the degradation of unstable or damaged proteins. UBR1-7, which are members of hundreds of E3 ubiquitin ligases, recognize and regulate the half-life of specific proteins on the basis of their N-terminal sequences ("N-end rule"). In seven individuals with intellectual disability, epilepsy, ptosis, hypothyroidism, and genital anomalies, we uncovered bi-allelic variants in UBR7. Their phenotype differs significantly from that of Johanson-Blizzard syndrome (JBS), which is caused by bi-allelic variants in UBR1, notably by the presence of epilepsy and the absence of exocrine pancreatic insufficiency and hypoplasia of nasal alae. While the mechanistic etiology of JBS remains uncertain, mutation of both Ubr1 and Ubr2 in the mouse or of the C. elegans UBR5 ortholog results in Notch signaling defects. Consistent with a potential role in Notch signaling, C. elegans ubr-7 expression partially overlaps with that of ubr-5, including in neurons, as well as the distal tip cell that plays a crucial role in signaling to germline stem cells via the Notch signaling pathway. Analysis of ubr-5 and ubr-7 single mutants and double mutants revealed genetic interactions with the Notch receptor gene glp-1 that influenced development and embryo formation. Collectively, our findings further implicate the UBR protein family and the Notch signaling pathway in a neurodevelopmental syndrome with epilepsy, ptosis, and hypothyroidism that differs from JBS. Further studies exploring a potential role in histone regulation are warranted given clinical overlap with KAT6B disorders and the interaction of UBR7 and UBR5 with histones.

Stellate cells are in utero markers of pancreatic disease in cystic fibrosis.

BACKGROUND: Pancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic fibrosis (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and the replacement of acinar tissue with cystic lesions and fibrosis is a progressive phenotype that may later lead to diabetes. Little is known about the initiating events in the fibrotic process though it may be a sequela of inflammation in the pancreatic ducts resulting from loss of CFTR impairing normal fluid secretion. Here we use a sheep model of CF (CFTR-/-) to examine the evolution of pancreatic disease through gestation. METHODS: Fetal pancreas was collected at six time points from 50-days of gestation through to term, which is equivalent to ~ 13 weeks to term in human. RNA was extracted from tissue for bulk RNA-seq and single cells were prepared from 80-day, 120-day and term samples for scRNA-seq. Data were validated by immunochemistry. RESULTS: Transcriptomic evidence from bulk RNA-seq showed alterations in the CFTR-/- pancreas by 65-days of gestation, which are accompanied by marked pathological changes by 80-days of gestation. These include a fibrotic response, confirmed by immunostaining for COL1A1, αSMA and SPARC, together with acinar loss. Moreover, using scRNA-seq we identify a unique cell population that is significantly overrepresented in the CFTR-/- animals at 80- and 120-days gestation, as are stellate cells at term. CONCLUSION: The transcriptomic changes and cellular imbalance that we observe likely have pivotal roles in the evolution of CF pancreatic disease and may provide therapeutic opportunities to delay or prevent pancreatic destruction in CF.

Pancreatic Surgery in Children: Complex, Safe, and Effective.

OBJECTIVE: The aim of this study was to assess indications for and report outcomes of pancreatic surgery in pediatric patients. BACKGROUND: Indications for pancreatic surgery in children are rare and data on surgical outcomes after pediatric pancreatic surgery are scarce. METHODS: All children who underwent pancreatic surgery at a tertiary hospital specializing in pancreatic surgery between 2003 and 2022 were identified from a prospectively maintained database. Indications, surgical procedures, and perioperative as well as long-term outcomes were analyzed. RESULTS: In total, 73 children with a mean age of 12.8 years (range: 4 mo to 18 y) underwent pancreatic surgery during the observation period. Indications included chronic pancreatitis (n=35), pancreatic tumors (n=27), and pancreatic trauma (n=11). Distal pancreatectomy was the most frequently performed procedure (n=23), followed by pancreatoduodenectomy (n=19), duodenum-preserving pancreatic head resection (n=10), segmental pancreatic resection (n=7), total pancreatectomy (n=3), and others (n=11). Postoperative morbidity occurred in 25 patients (34.2%), including 7 cases (9.6%) with major complications (Clavien-Dindo≥III). There was no postoperative (90-d) mortality. The 5-year overall survival was 90.5%. The 5-year event-free survival of patients with chronic pancreatitis was 85.7%, and 69.0% for patients with pancreatic tumors. CONCLUSION: This is the largest single-center study on pediatric pancreatic surgery in a Western population. Pediatric pancreatic surgery can be performed safely. Centralization in pancreatic centers with high expertise in surgery of adult and pediatric patients is important as it both affords the benefits of pancreatic surgery experience and ensures that surgical management is adapted to the specific needs of children.

Multistate Model of the Natural History of Inflammatory Pancreatic Diseases: A Nationwide Population-based Cohort Study.

BACKGROUND & AIMS: Understanding the nature of inflammatory pancreatic diseases is essential for planning health care system requirements and interventions. The aim of this study was to quantify the trajectories of inflammatory pancreatic diseases and their association with pancreatic cancer in a population-based setting. METHODS: National health registries were used to identify all Danish residents (18 years or older) in the period from 2000 through 2018 with incident cases of acute pancreatitis (AP), recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. We used a multistate model to examine transitions from a healthy state to intermediate states of acute pancreatic inflammation (AP and RAP) to chronic states (CP and pancreatic cancer) and, ultimately, death. Results were reported as transition incidence rates per 1000 person-years with 95% CIs. RESULTS: There were 4,663,864 individuals included (mean age, 46 years; 51% were women). During a mean follow-up of 16.8 years, 31,396 individuals were diagnosed with incident AP, 5546 with RAP, 8898 with CP, and 18,182 with pancreatic cancer. The cumulative incidence of pancreatitis (acute and chronic) during the study period was 0.80% (95% CI, 0.79%-0.80%). The transition incidence rates to CP were 12.1 (95% CI, 8.1-18.1) from AP, 46.8 (95% CI, 31.6-69.3) from RAP, and 0.07 (95% CI, 0.04-0.13) from a healthy state. Similar patterns were observed for transitions to pancreatic cancer. Most patients diagnosed with CP (64.2%) and pancreatic cancer (96.4%) transitioned directly from a healthy state. Among patients with pancreatitis, 41.0% (95% CI, 40.5%-41.5%) died during follow-up. CONCLUSIONS: The study findings revealed an increased risk of CP and pancreatic cancer in patients with a history of AP. However, most patients with CP and pancreatic cancer transitioned directly from a healthy state.

Associations of Intrapancreatic Fat Deposition With Incident Diseases of the Exocrine and Endocrine Pancreas: A UK Biobank Prospective Cohort Study.

INTRODUCTION: To investigate whether increased intrapancreatic fat deposition (IPFD) heightens the risk of diseases of the exocrine and endocrine pancreas. METHODS: A prospective cohort study was conducted using data from the UK Biobank. IPFD was quantified using MRI and a deep learning-based framework called nnUNet. The prevalence of fatty change of the pancreas (FP) was determined using sex- and age-specific thresholds. Associations between IPFD and pancreatic diseases were assessed with multivariate Cox-proportional hazard model adjusted for age, sex, ethnicity, body mass index, smoking and drinking status, central obesity, hypertension, dyslipidemia, liver fat content, and spleen fat content. RESULTS: Of the 42,599 participants included in the analysis, the prevalence of FP was 17.86%. Elevated IPFD levels were associated with an increased risk of acute pancreatitis (hazard ratio [HR] per 1 quintile change 1.513, 95% confidence interval [CI] 1.179-1.941), pancreatic cancer (HR per 1 quintile change 1.365, 95% CI 1.058-1.762) and diabetes mellitus (HR per 1 quintile change 1.221, 95% CI 1.132-1.318). FP was also associated with a higher risk of acute pancreatitis (HR 3.982, 95% CI 2.192-7.234), pancreatic cancer (HR 1.976, 95% CI 1.054-3.704), and diabetes mellitus (HR 1.337, 95% CI 1.122-1.593, P = 0.001). DISCUSSION: FP is a common pancreatic disorder. Fat in the pancreas is an independent risk factor for diseases of both the exocrine pancreas and endocrine pancreas.

Robotic Pancreatoduodenectomy in Portal Annular Pancreas Using a Hanging Maneuver with Indocyanine Green Fluorescence Imaging.

BACKGROUND: Sufficient knowledge and surgical management of portal annular pancreas (PAP) are essential for pancreatic surgery. As PAP is a relatively rare pancreatic anomaly, few studies have described surgical techniques for patients with PAP undergoing robotic pancreatoduodenectomy (RPD). PATIENTS AND METHODS: An 82-year-old female patient who underwent RPD presented with distal cholangiocarcinoma and type III PAP (the fusion of the uncinate process with the anteportal main pancreatic duct). After the Kocher maneuver and stomach transection, the pancreas was transected into the neck of the anteportal portion. The retroportal portion was dissected, encircled with hanging tape, and compressed. Blood supply from the mesenteric vessels was confirmed using indocyanine green (ICG) fluorescence imaging. Subsequently, the retroportal portion was stapled. CONCLUSIONS: This study demonstrates a unique surgical technique for type III PAP using the hanging maneuver with ICG fluorescence imaging. Surgeons should decide on the surgical strategy on the basis of the fusion and ductal anatomy of the pancreas.

Video-Based Indocyanine Green Fluorescence Applied to Robotic Duodenum-Preserving Pancreatic Head Resection.

BACKGROUND: Duodenum-preserving pancreatic head resection (DPPHR) serves as a surgical intervention for managing benign and low-grade malignant neoplasms located in the head of the pancreas. This surgical approach enables the thorough excision of pancreatic head lesions, reducing the necessity for digestive tract reconstruction and enhancing the patient's quality of life.1 Performing a minimally invasive DPPHR is a complex surgical procedure, particularly when safeguarding the bile duct and the pancreaticoduodenal arterial arch. Robotic surgery is among the latest innovations in minimally invasive surgery and is widely used in many surgical specialties. It offers advantages such as rotatable surgical instruments, muscle tremor filters and up to 10-15 times three dimensional (3D) visual field,2 and achieves high flexibility and accuracy in surgical operations. Indocyanine green (ICG) fluorescence imaging technology is also applied to provide real-time intraoperative assessment of the biliary system and blood supply, which helps maintain the biliary system's integrity.3,4 We first report the complete procedure of ICG applied to the da Vinci robotic Xi system for preserving the DPPHR. METHODS: A 48-year-old female patient was diagnosed with pancreatic duct stones, chronic pancreatitis, and pancreatogenic diabetes. Enhanced computed tomography (CT) scans revealed pancreatic head stones, pancreatic atrophy, scattered calcifications, and a dilated pancreatic duct. An attempt at endoscopic retrograde cholangiopancreatography (ERCP) treatment was abandoned during hospitalization due to unsuccessful catheterization. Following informed consent from the patient and her family, a robotic DPPHR was conducted utilizing ICG fluorescence imaging technology. Approximately 60 min before the surgery, 2 mg of ICG was injected via the peripheral vein. The individual was positioned in a reclined posture with the upper part of the bed raised to an angle of 30° and a leftward tilt of 15°. Upon entering the abdominal cavity, existing adhesions were meticulously separated and the gastrocolic ligament was opened to expose the pancreas. The lower part of the pancreas was separated and the superior mesenteric vein (SMV) was identified at the inferior boundary of the pancreatic neck. The pancreas was cut upward and the pancreatic duct was severed using scissors. Dissection of the lateral wall of the portal vein-SMV in the pancreatic head segment was performed. Meticulous dissection was carried out along the pancreatic tissue, retracting the uncinate process of the pancreas in an upward and rightward direction. During the dissection, caution was exercised to protect the anterior and posterior pancreaticoduodenal arterial arch. By using ICG fluorescence imaging, the path of the common bile duct was identified and verified. Caution was exercised to avoid injuring the bile duct. After isolating the CBD, the head and uncinate process of the pancreas was entirely excised. Under the fluorescence imaging mode, the wholeness of the CBD was scrutinized for any potential seepage of the contrast agent. Ultimately, a Roux-en-Y end-to-side pancreaticojejunostomy (duct to mucosa) was executed. RESULTS: The surgery took 265 min and the estimated blood loss was about 150 mL. Without any postoperative complications, the patient was released from the hospital 13 days following the surgery. Postoperative pathology confirmed pancreatic duct stones and chronic pancreatitis. We have successfully performed four cases of robotic DPPHR using this technique, with only one patient experiencing a postoperative complication of pulmonary embolism. All patients were discharged successfully without any further complications. CONCLUSIONS: Employing ICG fluorescence imaging in a robotic DPPHR has been demonstrated to be both secure and achievable. This technique potentially provides novel therapeutic perspectives, particularly for patients with ambiguous delineation between pancreatic and biliary ductal structures.

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries.

BACKGROUND: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide. METHODS: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters. RESULTS: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 per cent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 per cent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 per cent; however, it was 41 per cent in low-to-middle- compared with 19 per cent in very high-HDI countries. CONCLUSION: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761).

Pancreatic surgery can sometimes lead to health problems afterwards. Although some top hospitals report good results, it is not clear how patients are doing all over the world. The aim was to find out how people are recovering after pancreatic surgery in different countries, and to see whether where they live affects their health outcomes after pancreatic surgery. The health records of 4223 patients from 67 countries who had pancreatic surgery in a 3-month interval in 2021 were studied, especially looking at how many people faced serious complications or passed away within 90 days of the surgery. Almost 7 in 10 patients faced some health problems after operation. The chance of having a major health issue or dying after the surgery was higher in countries with fewer resources and less developed healthcare. For example, 10 of 100 patients died after the surgery in these countries, but only 5 of 100 patients did in richer countries. What stands out is that countries with fewer resources have a tougher time getting patients back to health when things go wrong after surgery. It is hoped that doctors and medical groups worldwide can work together to improve these outcomes and give everyone the best chance of recovering well after pancreatic surgery.

Hypothyroidism and subclinical hypothyroidism are associated with fatty pancreas (Non-Alcoholic Fatty Pancreas Disease).

OBJECTIVES: Increasing visceral fat deposition with raised prevalence of obesity and metabolic syndrome is associated with many adverse conditions, especially cardiovascular diseases and diabetes. Although there are many studies that investigate hepatic steatosis in hypothyroidism and subclinical hypothyroidism, to the best of our knowledge, there is no study investigating its relationship with pancreatic steatosis. In the present study, the purpose was to investigate this relationship. METHODS: Physical and biochemical characteristics of 30 hypothyroid, 30 subclinical hypothyroid, and 30 euthyroid volunteers were recorded in this cross-sectional study. Liver and pancreatic steatosis were evaluated with ultrasonography. RESULTS: It was found that pancreatic steatosis was increased in hypothyroid and subclinical groups when compared to the control group, and hepatic steatosis was increased in the subclinical group when compared to the control group (steatosis; p = 0.002, p = 0.004, p = 0.001, p = 0.002, p = 0.002, p = 0.004). Pancreatic steatosis was positively correlated with age, hepatic steatosis, height, weight, BMI, waist circumference, hip circumference, hemoglobin, Insulin, alanine aminotransferase, Triglyceride, Creatinine, and gamma-glutamyltransferase and was negatively correlated with total cholesterol, high-density lipoproteins. CONCLUSIONS: The prevalence of pancreatic steatosis was found to be increased in hypothyroidism and subclinical hypothyroidism when compared with the euthyroid control group.

The burden of recurrence acute pancreatitis and annual event rates are underestimated because of high rates of home self-management.

BACKGROUND/OBJECTIVES: The event-rate of recurrent acute pancreatitis (RAP) in patient populations is critical for powering research studies. We hypothesize that some patients manage RAP attacks at home, reducing event rate estimations based on counting emergency department (ED) visits and hospitalizations only. The aim of this study was to determine the rates of home self-management of recurrent acute pancreatitis compared to ED visits and hospitalizations. METHODS: An anonymous 8-question survey was sent to 1825 individuals on an email list of individuals with a history of acute pancreatitis (AP) or chronic pancreatitis or interest in pancreatic diseases. Question were designed to identify subjects with RAP within the past 2 years and to subdivide patients based on having a chronic pain syndrome or not. RESULTS: After an initial email request and one reminder a total of 194 subjects responded with 98 RAP subjects suitable for analysis. Annual AP events included an average of 1.44 hospitalizations, 1.37 ED visits, 2.46 disrupted work/school/social engagements, and 3.95 pancreatitis-like pain attacks per year. Patients with RAP average 6.8 RAP events per year with 58.4 % managed at home. CONCLUSIONS: The burden of disease in patients with RAP is significantly underestimated, especially for patients with chronic pain. Future studies should include measures to capture RAP events managed at home and utilize methods of documenting RAP events.

Skeletal muscle mass and function are affected by pancreatic atrophy, pancreatic exocrine insufficiency and poor nutritional status in patients with chronic pancreatitis.

BACKGROUND/OBJECTIVE: Previous studies have demonstrated that sarcopenia is frequently observed in patients with chronic pancreatitis (CP). However, most studies have defined sarcopenia solely based on skeletal muscle (SM) loss, and muscle weakness such as grip strength (GS) reduction has not been considered. We aimed to clarify whether SM loss and reduced GS have different associations with clinical characteristics and pancreatic imaging findings in patients with CP. METHODS: One hundred two patients with CP were enrolled. We defined SM loss by the SM index at the third lumbar vertebra on CT (<42 cm2/m2 for males and <38 cm2/m2 for females), and reduced GS by < 28 kg for males and <18 kg for females. RESULTS: Fifty-seven (55.9 %) patients had SM loss, 21 (20.6 %) had reduced GS, and 17 (16.7 %) had both. Patients with SM loss had lower body mass index, weaker GS, higher Controlling Nutritional Status score, lower serum lipase level, and lower urinary para-aminobenzoic acid excretion rate, suggesting worse nutritional status and pancreatic exocrine insufficiency. On CT, main pancreatic duct dilatation and parenchymal atrophy were more frequent in patients with SM loss than in those without it. Patients with reduced GS were older and had worse nutritional status than those without it. CONCLUSIONS: SM loss was associated with pancreatic exocrine insufficiency, low nutritional status, and pancreatic imaging findings such as parenchymal atrophy and main pancreatic duct dilatation, whereas older age and low nutritional status led to additional reduced GS.

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

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

Lumen-apposing metal stents for the treatment of pancreatic and peripancreatic fluid collections and bleeding risk: a propensity matched study.

INTRODUCTION: Endoscopic ultrasound (EUS)-guided drainage of symptomatic pancreatic fluid collections (PFCs) using the Hot-Axios device has recently been associated with a significant risk of bleeding. This adverse event (AE) seems to occur less frequently with the use of a different device, the Spaxus stent. The aim of the current study was to compare the rates of bleeding between the two stents. METHODS: Patients admitted for treatment of PFCs by EUS plus lumen-apposing metal stent in 18 endoscopy referral centers between 10 July 2019 and 28 February 2022 were identified and their outcomes compared using a propensity-matching analysis. RESULTS: 363 patients were evaluated. After a 1-to-1 propensity score match, 264 patients were selected (132 per group). The technical and clinical success rates were comparable between the two groups. Significantly more bleeding requiring transfusion and/or intervention occurred in the Hot-Axios group than in the Spaxus group (6.8% vs. 1.5%; P = 0.03); stent type was a significant predictor of bleeding in both univariate and multivariate regression analyses (P = 0.03 and 0.04, respectively). Bleeding necessitating arterial embolization did not however differ significantly between the two groups (3.0% vs. 0%; P = 0.12). In addition, the Hot-Axios was associated with a significantly higher rate of overall AEs compared with the Spaxus stent (9.8% vs. 3.0%; P = 0.04). CONCLUSION: Our study showed that, in patients with PFCs, bleeding requiring transfusion and/or intervention occurred significantly more frequently with use of the Hot-Axios stent than with the Spaxus stent, although this was not the case for bleeding requiring embolization.

Micelle-based fluorogenic sensing of trypsin: a sensitive method in pancreatic disease diagnosis.

Protamine-mediated micellar aggregates, featuring an AIE-based fluorescent sensor, facilitate efficient detection of trypsin activity. This method enables the detection of trypsin at exceptionally low concentrations (0.01-0.1 µg mL-1) in urine, demonstrating its potential for early clinical diagnosis of trypsin-related pancreatic diseases.