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.

Prevalence of Pancreatic Steatosis and Its Associated Factors in Turkey: A Nation-Wide Multicenter Study.

BACKGROUND/AIMS:  Pancreatic steatosis (PS) is a pathology associated with metabolic syndrome (MS), endocrin and exocrine disfunctions of the pancreas, and fatty liver. The data on the frequency of PS are very limited. We aimed to evaluate the frequency of PS detected by transabdominal ultrasonography (TAU) in gastroenterology clinics located in different geographical regions of Turkey and the factors associated with it. MATERIALS AND METHODS:  Volunteers were evaluated by TAU for PS and hepatosteatosis (HS), and its degree. Pancreatic stiffness was evaluated by ultrasonographic shear wave elastography (SWE). All demographic, physical, and biochemical parametres were measured. RESULTS:  A total of 1700 volunteers from 14 centers throughout Turkey were included in the study. Mean age was 48.03 ± 20.86 years (56.9% female). Prevalance of PS was detected in 68.9%. In the PS group, age, body mass index (BMI), waist circumference, systolic blood pressure, fasting blood glucose (FBG), lipid levels, insulin resistance, diabetes mellitus, hypertension, MS frequency, and pancreatic SWE score were increasing, and fecal elastase level was decreasing in correlation with the degree of PS. The frequency of HS was 55.5%. Hepatosteatosis [odds ratio (OR): 9.472], increased age (OR: 1.02), and BMI (OR: 1.089) were independent risk factors for the occurrence of PS. Lean-PS rate was 11.8%. The lean-PS group was predominantly female and younger than non-lean PS. Also it has lower blood pressure, FBG, liver enzymes, lipid levels, and HS rates. CONCLUSION:  The frequency of PS was found 68.9% in Turkey. Its relationship was determined with age, BMI, HS, MS (and its components), pancreatic stiffness, and fecal elastase level.

Pancreas Fine Needle Aspiration: Current and Future Impact on Patient Care.

Pancreatic lesions can be solid or cystic and comprise a wide range of benign, premalignant, and malignant entities. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the current primary sampling method for the preoperative diagnosis of pancreatic lesions. Optimal handling of cytology/small tissue specimens is critical to ensure that the often-scant diagnostic material is appropriately utilized for ancillary and/or molecular studies when appropriate. Ultimately, evaluation of EUS-FNA cytology and small biopsy material can provide accurate and timely diagnoses to guide patient management and triage them to surveillance or surgical intervention.

An Unusual Presentation of Extrapulmonary Tuberculosis in a Fibrocalculous Pancreatic Diabetes Patient.

Fibrocalculous pancreatic diabetes (FCPD) mellitus is a distinct type of diabetes that arises from chronic calcification of the pancreas in young, nonalcoholic individuals, predominantly in tropical regions. The characteristic triad of FCPD includes diabetes, abdominal pain, and steatorrhea. Additional notable features of the disease are its early age of onset, the presence of large intraductal stones, rapid disease progression, and a heightened risk of developing pancreatic cancer. Tuberculosis (TB) is a health concern worldwide and is responsible for a major health burden in developing countries like India. TB involving any organ other than the lungs is diagnosed as extrapulmonary tuberculosis (EPTB). EPTB with musculoskeletal involvement is often a difficult and delayed diagnosis because of unusual clinical presentations.

Current and Emerging Applications of Artificial Intelligence (AI) in the Management of Pancreatobiliary (PB) disorders.

PURPOSE OF REVIEW: In this review, we aim to summarize the existing literature and future directions on the use of artificial intelligence (AI) for the diagnosis and treatment of PB (pancreaticobiliary) disorders. RECENT FINDINGS: AI models have been developed to aid in the diagnosis and management of PB disorders such as pancreatic adenocarcinoma (PDAC), pancreatic neuroendocrine tumors (pNETs), acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis, choledocholithiasis, indeterminate biliary strictures, cholangiocarcinoma and endoscopic procedures such as ERCP, EUS, and cholangioscopy. Recent studies have integrated radiological, endoscopic and pathological data to develop models to aid in better detection and prognostication of these disorders. AI is an indispensable proponent in the future practice of medicine. It has been extensively studied and approved for use in the detection of colonic polyps. AI models based on clinical, laboratory, and radiomics have been developed to aid in the diagnosis and management of various PB disorders and its application is ever expanding. Despite promising results, these AI-based models need further external validation to be clinically applicable.

Positive health: An integrated quantitative approach in patients with chronic gastrointestinal and hepato-pancreatico-biliary disorders.

BACKGROUND: The concept of positive health (PH) supports an integrated approach for patients by taking into account six dimensions of health. This approach is especially relevant for patients with chronic disorders. Chronic gastrointestinal and hepato-pancreatico-biliary (GI-HPB) disorders are among the top-6 of the most prevalent chronically affected organ systems. The impact of chronic GI-HPB disorders on individuals may be disproportionally high because: (1) The affected organ system frequently contributes to a malnourished state; and (2) persons with chronic GI-HPB disorders are often younger than persons with chronic diseases in other organ systems. AIM: To describe and quantify the dimensions of PH in patients with chronic GI-HPB disorders. METHODS: Prospective, observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GI-HPB disorder attending the Outpatient Department of the Maastricht University Medical Center. Validated questionnaires and data from patient files were used to quantify the six dimensions of PH. Internal consistency was tested with McDonald's Omega. Zero-order Pearson correlations and t-tests were used to assess associations and differences. A P value < 0.05 was considered significant. RESULTS: The GI-HPB patients scored significantly worse in all dimensions of PH compared to control data or norm scores from the general population. Regarding quality of life, participation and daily functioning, GI-HPB patients scored in the same range as patients with chronic disorders in other organ systems, but depressive symptoms (in 35%) and malnutrition (in 45%) were more frequent in patients with chronic GI-HPB disorders. Intercorrelation scores between the six dimensions were only very weak to weak, forcing us to quantify each domain separately. CONCLUSION: All six dimensions of PH are impaired in the GI-HPB patients. Malnutrition and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.

Pancreatic Crosstalk in the Disease Setting: Understanding the Impact of Exocrine Disease on Endocrine Function.

The exocrine and endocrine are functionally distinct compartments of the pancreas that have traditionally been studied as separate entities. However, studies of embryonic development, adult physiology, and disease pathogenesis suggest there may be critical communication between exocrine and endocrine cells. In fact, the incidence of the endocrine disease diabetes secondary to exocrine disease/dysfunction ranges from 25% to 80%, depending on the type and severity of the exocrine pathology. Therefore, it is necessary to investigate how exocrine-endocrine "crosstalk" may impact pancreatic function. In this article, we discuss common exocrine diseases, including cystic fibrosis, acute, hereditary, and chronic pancreatitis, and the impact of these exocrine diseases on endocrine function. Additionally, we review how obesity and fatty pancreas influence exocrine function and the impact on cellular communication between the exocrine and endocrine compartments. Interestingly, in all pathologies, there is evidence that signals from the exocrine disease contribute to endocrine dysfunction and the progression to diabetes. Continued research efforts to identify the mechanisms that underlie the crosstalk between various cell types in the pancreas are critical to understanding normal pancreatic physiology as well as disease states. © 2024 American Physiological Society. Compr Physiol 14:5371-5387, 2024.

Endoscopic ultrasound-guided pancreatic duct drainage: a comprehensive state of the art review.

INTRODUCTION: Endoscopic retrograde pancreatography (ERP) has traditionally been the standard modality for pancreatic endotherapy. However, in certain situations, failure of retrograde ductal access may warrant an alternative modality of drainage. This can occur in various settings like difficult and/or surgically altered anatomy or duodenal obstruction. Endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD) is a relatively newer addition to the armamentarium for endoscopic access to the PD. AREAS COVERED: This comprehensive state-of-art review aims to give an overview of the indications, technical details, different approaches, and outcomes of EUS-PDD, with the latest evidence available in scientific literature. EXPERT OPINION: Akin to its biliary drainage counterpart, EUS-PDD enables an EUS-assisted-ERP using rendezvous technique or EUS-guided drainage through transmural stenting. The technique has evolved over the ensuing years with multitude of accessories, approaches, and devices to optimize the outcomes. However, the technical success and adverse events rates need to be further improved. Additionally, it has a steep learning curve with requirements of advanced technical skill and optimum infrastructure back-up. Meticulous patient selection, precise knowledge of ductal anatomy, appropriate approach, and carefully chosen accessories can improve its clinical outcomes.

Endoscopic approach for biliopancreatic disease after pancreaticoduodenectomy: a 10-year single-center experience.

BACKGROUND AND AIM: In surgically altered anatomy (SAA), endoscopic retrograde cholangiopancreatography (ERCP) can be challenging, and it remains debatable the choice of the optimal endoscopic approach within this context. We aim to show our experience and evaluate the technical and clinical success of endoscopic treatment performed in the setting of adverse events (AE) after pancreaticoduodenectomy (PD). METHODS: This study was conducted on a retrospective cohort of patients presenting biliopancreatic complications after PD from 01/01/2012 to 31/12/2022. All patients underwent ERCP at our Endoscopy Unit. Clinical, instrumental data, and characteristics of endoscopic treatments were collected. RESULTS: 133 patients were included (80 M, mean age = 65 y.o.) with a total of 296 endoscopic procedures (median = 2 procedures/treatment). The indications for ERCP were mainly biliary AE (76 cases, 57.1%). Technical success was obtained in 121 patients of 133 (90.9%). 112 out of 133 (84.2%) obtained clinical success. Nine patients out of 112 (8%) experienced AEs. Clinical success rates were statistically different between patients with biliary or pancreatic disease (93.4% vs 73.6%, p < 0.0001). Septic patients were 38 (28.6%) and showed a worse prognosis than non-septic ones (clinical success: 65.7% vs 91.5%, p = 0.0001). During follow-up, 9 patients (8%), experienced recurrence of the index biliopancreatic disease with a median onset at 20 months (IQR 6-40.1). CONCLUSION: Our case series demonstrated that the use of a pediatric colonoscope in ERCP procedures for patients with AEs after PD is both safe and effective in treating the condition, even in a long-term follow-up.

Label-free differentiation of pancreatic pathologies from normal pancreas utilizing end-to-end three-dimensional multimodal networks on CT.

AIMS: To investigate the utilization of an end-to-end multimodal convolutional model in the rapid and accurate diagnosis of pancreatic diseases using abdominal CT images. MATERIALS AND METHODS: In this study, a novel lightweight label-free end-to-end multimodal network (eeMulNet) model was proposed for the rapid and precise diagnosis of abnormal pancreas. The eeMulNet consists of two steps: pancreatic region localization and multimodal CT diagnosis integrating textual and image data. A research dataset comprising 715 CT scans with various types of pancreas diseases and 228 CT scans from a control group was collected. The training set and independent test set for the multimodal classification network were randomly divided in an 8:2 ratio (755 for training and 188 for testing). RESULTS: The eeMulNet model demonstrated outstanding performance on an independent test set of 188 CT scans (Normal: 45, Abnormal: 143), with an area under the curve (AUC) of 1.0, accuracy of 100%, and sensitivity of 100%. The average testing duration per patient was 41.04 seconds, while the classification network took only 0.04 seconds. CONCLUSIONS: The proposed eeMulNet model offers a promising approach for the diagnosis of pancreatic diseases. It can support the identification of suspicious cases during daily radiology work and enhance the accuracy of pancreatic disease diagnosis. The codes and models of eeMulNet are publicly available at Rudeguy1/eeMulNet (github.com).

The effects of caffeine on pancreatic diseases: the known and possible mechanisms.

Caffeine, a controversial substance, was once known to be addictive and harmful. In recent years, new effects of caffeine on the human body have been confirmed. Recent research over the past few decades has shown the potential of caffeine in treating pancreas-related diseases. This review aims to analyze the known and possible mechanisms of caffeine on pancreatic diseases and provides an overview of the current research status regarding the correlation between caffeine and pancreatic disease, while enhancing our understanding of their relationship.

Air pollutants and the risk of incident hepatobiliary diseases: A large prospective cohort study in the UK Biobank.

The association between air pollutants and hepatobiliary pancreatic diseases remains inconclusive. This study analyzed up to 247,091 participants of White European ancestry (aged 37 to 73 years at recruitment) from the UK Biobank, a large-scale prospective cohort with open access. An air pollution score was utilized to assess the combined effect of PM2.5, PM2.5-10, PM10, NO2, and NOX on total hepatobiliary pancreatic diseases, liver diseases, cholecyst diseases, and pancreatic diseases. Cox proportional hazard models were employed to evaluate the relationships between air pollutants and the incidence of these diseases. Restricted cubic spline regressions were used to examine the dose-response association between air pollutants and the risk of hepatobiliary pancreatic diseases. We identified 4865 cases of total hepatobiliary pancreatic diseases, over a median follow-up of 10.86 years. The air pollution scores were moderately associated with increased liver disease risk (HR = 1.009, 95 % CI: 1.004, 1.014), but not with cholecyst and pancreatic diseases. Among the individual air pollutants, PM2.5 (HR = 1.069, 95 % CI: 1.025, 1.115) and PM10 (HR = 1.036, 95 % CI: 1.011, 1.061) significantly increased liver disease risk. Males showed a higher risk of liver diseases with PM2.5 (HR = 1.075, 95 % CI: 1.015, 1.139). Additionally, individuals with overweight (HR = 1.125, 95 % CI: 1.052, 1.203), age ≥ 60 and ≤73 (HR = 1.098, 95 % CI: 1.028, 1.172), and alcohol intake ≥ 14 unit/week (HR = 1.078, 95 % CI: 1.006, 1.155) had a higher risk of developing liver diseases at high expose to PM2.5. This study suggests that prolonged exposure to ambient air pollutants may elevate the risk of liver diseases.

Establishment of a human induced pluripotent stem cell line (SDQLCHi079-A) from a patient with Johanson-Blizzard syndrome carrying heterozygous mutation in UBR1 gene.

Johanson-Blizzard syndrome (JBS) is an autosomal recessive disorder. We established an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a 2-year-old boy with Johanson-Blizzard syndrome carrying a compound heterozygous mutation of c.3167C>G (p.S1056X) and c.1911 + 14C>G(splicing) in the UBR1 gene. This iPSC line was free of exogenous gene, expressed stemness markers, exhibited differentiation potential, had normal karyotype and harbored the same mutations found in the patient. The iPSC cellline can serve as a disease model in drug development and novel personalized therapies.

An update on the endocrine manifestations of antiphospholipid syndrome.

Antiphospholipid Syndrome (APS), characterized by hypercoagulability and pregnancy morbidity, poses a significant clinical challenge when involving organ systems, such as the endocrine system. APS can directly and indirectly influence the anterior and posterior lobes of the pituitary gland. The thyroid gland exhibits involvement, especially in patients with positive anticardiolipin antibodies, yet the clinical significance of the relationship with APS remains elusive. The pancreas, often overlooked, manifests in diverse ways, from pancreatitis to implications in diabetes. Adrenal insufficiency emerges as a common endocrine manifestation of APS, with adrenal hemorrhage or infarction being a presenting manifestation. Adrenal gland involvement has also been reported in the context of catastrophic APS. Pregnancy complications and infertility might be effects of APS on the female ovaries, while testicular torsion and decreased sperm concentration and total sperm count have been reported as rare effects of APS on male testes.

Successful treatment of feline pancreatolithiasis associated with an ascending Providencia rettgeri infection using a novel surgical technique.

A 12-year-old female spayed Domestic Shorthair cat presented with a 4-day history of lethargy, inappetence and vomiting. Physical findings included a grade 2/6 heart murmur and cranial abdominal pain on palpation. Serum biochemistry revealed elevated total bilirubin and liver enzymes activities. Abdominal ultrasound revealed multiple pancreatoliths, cholelithiasis and dilation of the pancreatic duct. During exploratory laparotomy, catheterisation of the pancreatic duct with retrograde and orthograde flushing to remove the pancreatoliths was performed via a distal enterotomy and proximal left apical partial pancreatectomy respectively. Catheterisation and flushing of the common bile duct were performed to confirm patency prior to cholecystectomy. Bacterial culture of pancreatoliths, pancreatic tissue and bile grew a heavy, pure growth of Providencia rettgeri. Fluorescent immunostaining histopathology revealed clusters of rod-shaped bacteria within the pancreatic parenchyma and gall bladder mucosa. The cat received pradofloxacin for two weeks. She made a complete recovery and remained well at a six-month follow-up.

Minimally invasive versus open pancreatoduodenectomy in benign, premalignant, and malignant disease.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of laparoscopic or robot-assisted pancreatoduodenectomy versus open pancreatoduodenectomy for people with benign, premalignant, and malignant disease.