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The pancreas is an organ with both exocrine and endocrine functions, comprising a highly organized and complex tissue microenvironment composed of diverse cellular and non-cellular components. The impairment of microenvironmental homeostasis, mediated by the dysregulation of cell-to-cell crosstalk, can lead to pancreatic diseases such as pancreatitis, diabetes, and pancreatic cancer. Macrophages, key immune effector cells, can dynamically modulate their polarization status between pro-inflammatory (M1) and anti-inflammatory (M2) modes, critically influencing the homeostasis of the pancreatic microenvironment and thus playing a pivotal role in the pathogenesis of the pancreatic disease. This review aims to summarize current findings and provide detailed mechanistic insights into how alterations mediated by macrophage polarization contribute to the pathogenesis of pancreatic disorders. By analyzing current research comprehensively, this article endeavors to deepen our mechanistic understanding of regulatory molecules that affect macrophage polarity and the intricate crosstalk that regulates pancreatic function within the microenvironment, thereby facilitating the development of innovative therapeutic strategies that target perturbations in the pancreatic microenvironment. [ABSTRACT FROM AUTHOR]

Severe acute pancreatitis (SAP) begins with premature activation of enzymes, promoted by the immune system, triggering a potential systemic inflammatory response that leads to organ failure with increased mortality and a bleak prognosis. Interleukin-22 (IL-22) is a cytokine that may have a significant role in SAP. IL-22, a member of the IL-10 cytokine family, has garnered growing interest owing to its potential tissue-protective properties. Recently, emerging research has revealed its specific effects on pancreatic diseases, particularly SAP. This paper provides a review of the latest knowledge on the role of IL-22 and its viability as a therapeutic target in SAP. Highlights: 1. Interleukin-22 (IL-22) is a member of the IL-10 family of cytokines. 2. IL-22 is a potential indicator for monitoring organ dysfunction and severity of severe acute pancreatitis (SAP). 3. IL-22 acts as a protective factor against acinar cell damage by suppressing autophagy and reducing the infiltration of inflammatory cells. 4. IL-22 alleviate SAP-induced multiorgan injury. 5. IL-22 protect SAP-induced intestinal barrier damage. [ABSTRACT FROM AUTHOR]

The role of the intestinal microbiota in the diagnosis and treatment of pancreatic diseases is increasingly significant. Consequently, fecal microbiota transplantation (FMT) is emerging as a promising therapeutic avenue for various pancreatic disorders, including cancer, pancreatitis, and type 1 diabetes (T1D). This innovative procedure entails transferring gut microbiota from healthy donors to individuals affected by pancreatic ailments with the potential to restore intestinal balance and alleviate associated symptoms. FMT represents a pioneering approach to improve patient outcomes in pancreatic diseases, offering tailored treatments customized to individual microbiomes and specific conditions. Recent research highlights the therapeutic benefits of targeting the gut microbiota for personalized interventions in pancreatic disorders. However, a comprehensive understanding of the intricate interplay between gut microbiota and pancreatic physiology warrants further investigation. The necessity for additional studies and research endeavors remains crucial, especially in elucidating both adult and pediatric cases affected by pathological pancreatic conditions. [ABSTRACT FROM AUTHOR]

Background: Pancreatic fluid collections (PFCs) may recur after resolution with endoscopic transmural drainage (ETD) and standard stent removal (SSR). Herein, we compared the efficacy and safety of leaving long-term indwelling plastic stents (LTIS) vs. standard stent removal after PFC resolution with ETD. Methods: We performed a systematic review of MEDLINE, EMBASE, CINAHL, Scopus, and Cochrane databases from inception to September 2022. Full-text articles comparing long-term (> 6 months) outcomes of LTIS and SSR were eligible, as well as single-arm studies with ≥ 10 patients with LTIS. Two independent reviewers selected studies, extracted data, and assessed the risk of bias using the Newcastle–Ottawa Scale. Measured outcomes included the following: (A) PFC recurrence; (B) interventions for PFC recurrence; (C) technical success; and (D) adverse events (AEs). Meta-analysis was carried out using random-effects models. Results: We included 16 studies, encompassing 1285 patients. Compared to SSR after PFC resolution with ETD, LTIS was associated with significantly lower risk of PFC recurrence (3% vs. 23%; OR 0.22 [95%CI 0.09–0.52]; I2 = 45%) and need for interventions (2% vs. 14%; OR 0.35 [95%CI 0.16–0.78]; I2 = 0%). The superiority of LTIS on reducing PFC recurrence was found with walled-off necrosis, with or without disconnected pancreatic duct, and with placement of ≥ 2 LTIS. When using LTIS, the pooled proportion of AEs was 8% (95%CI 4–11%) and technical success was 93% (95%CI 86–99%). Conclusions: Our results show that LTIS after PFC resolution with ETD is feasible, safe, and superior to SSR in reducing the risk of PFC recurrence and need for interventions. [ABSTRACT FROM AUTHOR]

Background: The accumulation of fat in the pancreas has greater clinical significance. It is unclear, though, how much the intermediate variables influence the fat deposition in these depots. This study aimed to determine the relation of pancreatic steatosis to Diabetes Mellitus, Acute Pancreatitis and Pancreatic Cancer. Methods: This case-control study was conducted on fifty patients for pancreatic diseases in internal medicine department at Zagazig University Hospitals, equally divided into five groups; group I: 10 cases as a control group, group II: with fatty pancreas (FP), group III: with acute pancreatitis (AP), group IV: with Diabetes Mellitus (DM) and case group V: with pancreatic cancer (PC). Patients were subjected to full medical history, physical examination, laboratory investigations, and non-contrast Computed Tomography (CT). Results: Age and males were significant increased in group V (PValue= 0.003 and P=0.019 respectively). Body Mass Index (BMI) (P=0.001) and females (P=0.006) were higher among fatty pancreas patients. Pancreatic steatosis diagnosed by CT in FP representing 100%, in acute pancreatitis 60%, DM 80% and PC 70% of patients, and it was worse in FP group as 40% ware grade 4 (P <0.001). Fatty liver diagnosed by CT in 100% of FP patients, 70% in AP and DM groups and 60% in PC group and was worse in FP group as 80% grade 3 (P <0.001). grades of fatty liver and Low-Density Lipoprotein (LDL) cholesterol significantly independently associated with fatty pancreas (P<0.001). High lipids, diabetes and grades of fatty liver were significantly associated with fatty pancreas (P<0.001) and LDL and fatty liver are independent risk factors (P<0.001). Conclusion: Pancreatic steatosis is highly related to Diabetes Mellitus, Acute Pancreatitis and Pancreatic Cancer. [ABSTRACT FROM AUTHOR]

The aryl hydrocarbon receptor (AHR) serves as a ligand-activated transcription factor crucial for regulating fundamental cellular and molecular processes, such as xenobiotic metabolism, immune responses, and cancer development. Notably, a spectrum of endocrine-disrupting chemicals (EDCs) act as agonists or antagonists of AHR, leading to the dysregulation of pivotal cellular and molecular processes and endocrine system disruption. Accumulating evidence suggests a correlation between EDC exposure and the onset of diverse pancreatic diseases, including diabetes, pancreatitis, and pancreatic cancer. Despite this association, the mechanistic role of AHR as a linchpin molecule in EDC exposure-related pathogenesis of pancreatic diseases and cancer remains unexplored. This review comprehensively examines the involvement of AHR in EDC exposure-mediated regulation of pancreatic pathogenesis, emphasizing AHR as a potential therapeutic target for the pathogenesis of pancreatic diseases and cancer. [ABSTRACT FROM AUTHOR]

Background and Aim: More insight into the incidence of and factors associated with progression following a first episode of acute pancreatitis (AP) would offer opportunities for improvements in disease management and patient counseling. Methods: A long‐term post hoc analysis of a prospective cohort of patients with AP (2008–2015) was performed. Primary endpoints were recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. Cumulative incidence calculations and risk analyses were performed. Results: Overall, 1184 patients with a median follow‐up of 9 years (IQR: 7–11) were included. RAP and CP occurred in 301 patients (25%) and 72 patients (6%), with the highest incidences observed for alcoholic pancreatitis (40% and 22%). Pancreatic cancer was diagnosed in 14 patients (1%). Predictive factors for RAP were alcoholic and idiopathic pancreatitis (OR 2.70, 95% CI 1.51–4.82 and OR 2.06, 95% CI 1.40–3.02), and no pancreatic interventions (OR 1.82, 95% CI 1.10–3.01). Non‐biliary etiology (alcohol: OR 5.24, 95% CI 1.94–14.16, idiopathic: OR 4.57, 95% CI 2.05–10.16, and other: OR 2.97, 95% CI 1.11–7.94), RAP (OR 4.93, 95% CI 2.84–8.58), prior pancreatic interventions (OR 3.10, 95% CI 1.20–8.02), smoking (OR 2.33, 95% CI 1.14–4.78), and male sex (OR 2.06, 95% CI 1.05–4.05) were independently associated with CP. Conclusion: Disease progression was observed in a quarter of pancreatitis patients. We identified several risk factors that may be helpful to devise personalized strategies with the intention to reduce the impact of disease progression in patients with AP. [ABSTRACT FROM AUTHOR]

Congenital variants of the pancreas are being increasingly detected with the widespread use of modern imaging techniques. The underlying embryologic aberration predicts the final appearance of pancreatic development. It is essential to recognize these congenital variants, as many of these have been proven to be associated with pancreatic diseases like recurrent pancreatitis and chronic abdominal pain. Cross-sectional techniques like multidetector computed tomography and magnetic resonance cholangiopancreatography are the most used imaging techniques for the pancreas, where a radiologist comes across these variants. This pictorial aims to classify the type of variant anatomy of the pancreas, their imaging appearances, and their clinical significance. [ABSTRACT FROM AUTHOR]

Introduction: Serum amylase and lipase elevations are classically related to pancreatic diseases. Hyperamylasemia is noticed to various common non-pancreatic clinical conditions, however hyperlipasemia is considered the specific marker of pancreatic diseases. Methodology and Results: This paper set forth 3 cases of Diabetic Keto Acidosis that presented with abdominal pain which are initially misapprehended to be Acute Pancreatitis due to markedly raised serum amylase and lipase levels. Conclusion: Markedly raised amylase and lipase levels are also noticed in non-pancreatic diseases. Optimal clinical judgement plays an essential role in diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: The relation between biliary tree diseases and pancreatitis is not well-known in veterinary medicine. Anecdotally, hyperlipemia, pancreatic inflammation, and abnormalities of biliary flow are thought to play a role in the pathogenesis. The aim of the work was to study the frequency and features of pancreatic involvement in dogs with chronic biliary tree disease. We retrospectively included 81 dogs with both laboratory and ultrasound signs of chronic biliary tree disease. Medical records of the included dogs and their pancreatic involvement was recorded considering ultrasonographic features and/or biochemical alterations (Lipase DGGR). Fifty-eight dogs (72%) showed pancreatic involvement, suggesting that pancreatic status should be investigated in canine patients with chronic biliary tree disease. Canine chronic biliary tree disease (CBTD) is a suspected risk factor for pancreatic injury. The aim of this study was to evaluate the frequency and features of pancreatic involvement in canine CBTD, and their relationship with hyperlipemia and its severity. CBTD was defined as the increase in at least two of ALP, GGT, total bilirubin, cholesterol, and a biliary tree abnormal abdominal ultrasound (graded mild to severe). Pancreatic ultrasound appearance was recorded and classified as acute/chronic. Dogs were divided into a PBD group (pancreatic and biliary disease) and BD group (only biliary tree disease). PBD group was subgraded into a "pancreatic injury" and "pancreatitis" group. Eighty-one dogs were retrospectively included: 56 in the PBD group and 25 in the BD group. Of the PBD group, 20 had pancreatitis (15 chronic and 5 dogs acute). US score was mild in 64 dogs and moderate in 17 dogs, and it was not associated with evidence of pancreopathy. Sixty-six dogs had hyperlipemia (mild = 27 dogs; moderate-to-severe = 39 dogs) and no association with pancreopathy was found. Pancreatic injury was more frequent than pancreatitis in CBTD dogs. Although both acute and chronic pancreatic injury may be present, chronic forms were more frequent. Pancreatic injury should be considered in CBTD patients due its possible clinical significance. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is an acute inflammatory process of the pancreas, the incidence of which is increasing, and the management of which requires multidisciplinary intervention. Our work is a prospective analysis of 356 cases of BP collected in the emergency services, Visceral A and B surgery, and resuscitation of the Hassan II teaching hospital in Fez over a 2-year period from April 2017 to May 2019. The goal of our job is to analyze the epidemiological aspects of PA and mainly to verify the reliability and the feasibility of the new SIRS score in the evaluation of the severity of PA in our context. The mean age was 55±17.29 with a clear female predominance. The diagnosis of BP was established in front of an evocative clinical picture associated with lipasemia> 3x normal in 91.5% of cases. Abdominal CT revealed a predominance of PA stage E balthazar with 37.5% followed by stage C with 32.5%. Biliary etiology is predominant in 78.4% of cases followed by origin Admission SIRS was present in 48% of cases and was persistent beyond 48 hours in 18% of cases. All of the patients who developed a complication during BP had a positive SIRS at admission. The superinfection of the necrosis flows was present in 75.8% of the patients having a persistent SIRS beyond 48h. The complications were mainly dominated by the superinfection of the necrosis flows found in 15% of the cases. According to the Atlanta classification, we found : Medical treatment was initiated in all patients while endoscopic and surgical treatment were much less common In the light of our study, it was concluded that the SIRS score is a simple, precise and specific means for predicting and evaluating the severity of acute pancreatitis taking into account the drawbacks of other multifactorial scores. [ABSTRACT FROM AUTHOR]

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is the preferred technique for treating pathologies of the bile duct. It has been suggested that this procedure, combined with sphincterotomy, may influence the subsequent development of long-term complications. The main objective of this study was to determine the long-term complications of biliopancreatic disease after ERCP and their potential association with the development of biliopancreatic neoplasms. Methods: This retrospective cohort study included 576 patients who underwent ERCP (referred to as index ERCP) with sphincterotomy for benign biliary disease, with a minimum follow-up period of more than 2 years. Results: The incidence of long-term benign and neoplastic pathologies after ERCP was analyzed. The most common findings were recurrence of choledocholithiasis in 70 patients (12.1%), cholangitis "sine materia" in 27 patients (4.7%), and acute pancreatitis in 8 patients (1.4%). Eight patients (1.4%) developed hepatobiliopancreatic neoplasms, including 4 cases of pancreatic neoplasms (0.7%), 1 cholangiocarcinoma (0.2%), 1 ampulloma (0.2%), and 2 intrahepatic neoplasms (0.3%). Multivariate analysis revealed that factors such as age over 50 years, previous biliary surgery, diversion of the bile duct (BD) to the digestive tract, dilation of the BD, stent placement, biopsy, and cholecystectomy were factors associated with an increased risk of long-term benign complications. Conclusion: Endoscopic retrograde chola ngiop ancre atogr aphy with sphincterotomy is associated with an increased long-term risk of subsequent benign biliopancreatic disease. However, our data do not allow us to establish a direct relationship with the development of biliopancreatic neoplasms. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Primary pancreatic lymphoma is a rare disease that can mimic acute pancreatitis. Since the prognosis and approaches differ, clinicians should differentiate it from other pancreatic diseases, especially autoimmune pancreatitis and adenocarcinoma. [ABSTRACT FROM AUTHOR]

Objective Post-pancreatitis diabetes mellitus (PPDM) is a frequent complication of pancreatitis and is associated with an increased risk of adverse outcomes. Metformin is recommended for the treatment of PPDM, but evidence of its risk-benefit profile is limited. In a pharmaco-epidemiologic study, we investigated the association between metformin treatment and adverse outcomes in patients with PPDM. Design and Methods In a Danish nationwide population-based cohort study, we included adults (≥18 years) with incident PPDM or type 2 diabetes between 2009 and 2018. Post-pancreatitis diabetes mellitus was categorised into acute and chronic subtypes (PPDM-A and PPDM-C). Associations between metformin treatment and severe hypoglycaemia, major adverse cardiovascular events (MACE), and all-cause mortality were examined across the diabetes subgroups using Cox regression analysis. Treatments with metformin, insulin, and other glucose-lowering therapies were handled as time-varying exposures. Results We included 222 337 individuals with new-onset type 2 diabetes and 3781 with PPDM, of whom 2305 (61%) were classified as PPDM-A and 1476 (39%) as PPDM-C. Treatment with metformin was associated with a lower risk of severe hypoglycaemia (adjusted hazard ratio [HR] 0.41, 95% CI 0.27-0.62, P <.0001), MACE (HR 0.74, 95% CI 0.60-0.92, P =.0071), and all-cause mortality (HR 0.56, 95% CI 0.49-0.64, P <.0001) in patients with PPDM. In sensitivity analyses and among individuals with type 2 diabetes, metformin treatment exhibited comparable trends of risk reduction. Conclusions Metformin is associated with a lower risk of adverse outcomes, including all-cause mortality in patients with PPDM, supporting the use of metformin as a glucose-lowering therapy for these patients. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is an inflammatory disease of the pancreas. Iron is an essential element for life and is involved in many metabolic processes. Ferroptosis is a type of regulated cell death that is triggered by iron and oxidative stress. A well-established mouse AP model was adopted to study the role of iron and ferroptosis in the pathogenesis of pancreatitis. Mice were injected with cerulein to induce AP, and pancreatic tissue samples were analyzed to determine the pathology, cell death, iron deposition, expression of iron transporters, and lipid peroxidation. The role of iron was studied by giving mice extra iron or iron chelator. In vitro studies with acinar cells with ferroptosis activator and inhibitor were also performed to assess the inflammatory response. Iron was found accumulated in the pancreatic tissue of mice who suffered cerulein-induced pancreatitis. Cell death and lipid peroxidation increased in these tissues and could be further modulated by iron dextran or iron chelator. Mice given Hemin through gavage had reduced levels of GSH in pancreatic tissue and increased inflammatory response. Studies with acinar cells showed increased levels of lipid peroxidation and ferroptosis-specific mitochondrial damage when treated with ferroptosis inducer and inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Deuterium metabolic imaging (DMI) is a promising tool for investigating a tumor's biology, and eventually contribute in cancer diagnosis and prognosis. In DMI, [6,6′-2H2]-glucose is taken up and metabolized by different tissues, resulting in the formation of HDO but also in an enhanced formation of [3,3′-2H2]-lactate at the tumor site as a result of the Warburg effect. Recent studies have shown DMI's suitability to highlight pancreatic cancer in murine models by [3,3′-2H2]-lactate formation; an important question is whether DMI can also differentiate between these tumors and pancreatitis. This differentiation is critical, as these two diseases are hard to distinguish today radiologically, but have very different prognoses requiring distinctive treatments. Recent studies have shown the limitations that hyperpolarized MRI faces when trying to distinguish these pancreatic diseases by monitoring the [1-13C1]-pyruvate→[1-13C1]-lactate conversion. In this work, we explore DMI's capability to achieve such differentiation. Initial tests used a multi-echo (ME) SSFP sequence, to identify any metabolic differences between tumor and acute pancreatitis models that had been previously elicited very similar [1-13C1]-pyruvate→[1-13C1]-lactate conversion rates. Although ME-SSFP provides approximately 5 times greater signal-to-noise ratio (SNR) than the standard chemical shift imaging (CSI) experiment used in DMI, no lactate signal was observed in the pancreatitis model. To enhance lactate sensitivity further, we developed a new, weighted-average, CSI-SSFP approach for DMI. Weighted-average CSI-SSFP improved DMI's SNR by another factor of 4 over ME-SSFP—a sensitivity enhancement that sufficed to evidence natural abundance 2H fat in abdominal images, something that had escaped the previous approaches even at ultrahigh (15.2 T) MRI fields. Despite these efforts to enhance DMI's sensitivity, no lactate signal could be detected in acute pancreatitis models (n = 10; [3,3′-2H2]-lactate limit of detection < 100 µM; 15.2 T). This leads to the conclusion that pancreatic tumors and acute pancreatitis may be clearly distinguished by DMI, based on their different abilities to generate deuterated lactate. [ABSTRACT FROM AUTHOR]

Introduction: Acute pancreatitis (AP) is an inflammatory disease of the pancreas leading to pancreatic edema, bleeding, and necrosis. Acute pancreatitis is the leading cause of gastrointestinal-related hospitalization in most of the developing countries. A growing number of studies have focused on the association between blood glucose levels and AP outcomes of acute pancreatitis. The main aim of our study is to detect the ranges of blood glucose levels in pancreatitis disease. Material & Methods: This study was carried out after obtaining approval from the institutional ethics committee. A patient under inclusion criteria was selected for the study they were divided into three groups based on the severity of pancreatitis. In Group A 50 patients with mild pancreatitis, Group B 50 patients with moderate pancreatitis and Group C 50 patients with severe pancreatitis. All the patient's sign and symptoms, fasting blood glucose (FBS), postprandial blood glucose (PPBS), hemoglobin (Hb), neutrophils, and lymphocyte count was done. Then the patients were prescribed selective doses Insulin based on the Glycemic index and after 3 months of treatment, all the biochemical parameter investigation were repeated after 3 months. Results: As per the study majority of the patients were male under the age group 51 - 60 years (58.00%) in group A and in groups B & C majority of the patients were under the age group of 61 - 70 years there were 48.00% & 64.00% showing statistical insignificance (p<0.05) respectively. In this study, majority of the patients had Ascites (fluid buildup in the belly) - 148 (98.66%) followed by severe abdominal pain 146 (97.33%) as major symptoms. In group A patients, significant mean reduction was observed in FBS & PPBS 30.10±1.00 & 25.88 ± 0.30 (p<0.05) respectively and no significant was observed in group B & C of FBS and PPBS (p>0.05 respectively. There is no change in Hb, neutrophils, and leukocyte counts in all three groups. Conclusion: Patients with mild pancreatitis have shown statistically significant reduction in FBS & PPBS levels, as compared to patients with moderate and severe pancreatitis. [ABSTRACT FROM AUTHOR]

Pancreatic disorders during childhood are rare but associated with significant morbidity and mortality. The spectrum of pancreatic disorders in children range from acquired causes, such as drug-induced pancreatitis or pancreatic trauma to more complex congenital anomalies and inherited disorders to pancreatic neoplasms. We are presenting a series of six cases of rare pancreatic disorders in children with review of relevant literature. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is a common and potentially life-threatening inflammatory disease of the pancreas. Reactive oxygen species (ROS) play a key role in the occurrence and development of AP. With increasing ROS levels, the degree of oxidative stress and the severity of AP increase. However, diagnosing AP still has many drawbacks, including difficulties with early diagnosis and undesirable sensitivity and accuracy. Herein, we synthesized a semiconducting polymer nanoplatform (SPN) that can emit ROS-correlated chemiluminescence (CL) signals. The CL intensity increased in solution after optimization of the SPN. The biosafety of the SPN was verified in vitro and in vivo. The mechanism and sensitivity of the SPN for AP early diagnosis and severity assessment were evaluated in three groups of mice using CL intensity, serum marker evaluations and hematoxylin and eosin staining assessments. The synthetic SPN can be sensitively combined with different concentrations of ROS to produce different degrees of high-intensity CL in vitro and in vivo. Notably, the SPN shows an excellent correlation between CL intensity and AP severity. This nanoplatform represents a superior method to assess the severity of AP accurately and sensitively according to ROS related chemiluminescence signals. This research overcomes the shortcomings of AP diagnosis in clinical practice and provides a novel method for the clinical diagnosis of pancreatitis in the future. [ABSTRACT FROM AUTHOR]

Background : Acute and chronic pancreatitis constitute a continuum of inflammatory disease of the pancreas with an increasing incidence in most high-income countries. A subset of patients with a history of pancreatitis suffer from recurrence of acute pancreatitis attacks, which accelerate disease progression towards end-stage chronic pancreatitis with loss of exocrine and endocrine function. There is currently no available prophylactic treatment for recurrent acute pancreatitis apart from removing risk factors, which is not always possible. Pain is the primary symptom of acute pancreatitis, which induces the endogenous release of opioids. This may further be potentiated by opioid administration for pain management. Increased exposure to opioids leads to potentially harmful effects on the gastrointestinal tract, including, e.g. increased sphincter tones and decreased fluid secretion, which may impair pancreatic ductal clearance and elevate the risk for new pancreatitis attacks and accelerate disease progression. Peripherally acting µ-opioid receptor antagonists (PAMORAs) have been developed to counteract the adverse effects of opioids on the gastrointestinal tract. We hypothesize that the PAMORA naldemedine will reduce the risk of new pancreatitis attacks in patients with recurrent acute pancreatitis and hence decelerate disease progression. Methods: The study is a double-blind, randomized controlled trial with allocation of patients to either 0.2 mg naldemedine daily or matching placebo for 12 months. A total of 120 outpatients will be enrolled from five specialist centres in Denmark and Sweden. The main inclusion criteria is a history of recurrent acute pancreatitis (minimum of two confirmed pancreatitis attacks). The primary endpoint is time to acute pancreatitis recurrence after randomization. Secondary outcomes include changes in quality of life, gastrointestinal symptom scores, new-onset diabetes, exocrine pancreatic insufficiency, disease severity, health care utilization, adherence to treatment, and frequency of adverse events. Exploratory outcomes are included for mechanistic linkage and include the progression of chronic pancreatitis-related findings on magnetic resonance imaging (MRI) and changes in circulating blood markers of inflammation and fibrosis. Discussion: This study investigates if naldemedine can change the natural course of pancreatitis in patients with recurrent acute pancreatitis and improve patient outcomes. Trial registration: EudraCT no. 2021–000069-34. ClinicalTrials.gov NCT04966559. Registered on July 8, 2021. [ABSTRACT FROM AUTHOR]

Acute pancreatitis is one of the main causes of hospitalization for gastroenterological reason in the world. To date, the management of this disease apart from the etiological treatment, remains symptomatic. The correction of the hypovolemia induced in pancreatitis, is a cornerstone of management. Some authors defend the concept that the fluid resuscitation could influence the severity of the disease by limiting pancreatic ischemia and peripheral hypo-perfusion at the origin of organ failure. However, recent data show that aggressive fluid resuscitation can induce deleterious effects, in particular -volume overload, without inflecting the natural history of the disease. If the volume and the optimal modalities remain to be defined, the speed of initiation of the infusions could condition its impact. To date, it seems reasonable to favor balanced crystalloids and in particular Ringer's Lactate, not to exceed 3 ml/kg/h without questioning the relevance of the prescription. It is crucial to evaluate early and regularly in order to adapt prescriptions to initial hemodynamic status of the patient and to his response to infusion. The development of simple and relevant hemodynamic monitoring tools in this indication is a major challenge for the future. This mini-review aims to detail the role of fluid resuscitation in acute pancreatitis, its modalities, the expected benefits and the limits of this therapy. [ABSTRACT FROM AUTHOR]

Purpose: To define the pancreatic thickness on the transverse plane and apparent diffusion coefficient (ADC) values at multiple anatomical locations in the normal pancreas of children and to evaluate inter-rater and intra-rater reliability. Methods: Two reviewers measured the thickness and ADC values of the pancreas at four locations obtained from two different 1,5 Tesla MRI scanners [MAGNETOM Symphony (Siemens Medical Systems, Erlangen, Germany) and Signa HDxt(GE Healthcare, Milwaukee, WI, USA)]. Measurements were made based on 190 retrospective MRI examinations. Patients were distributed among ten age groups for thickness measurements and three age groups for ADC measurements between 0 and 18 years. Results: The thickness measurements from each segment of the pancreas were significantly correlated with patient age, height and weight (p < 0.01). Inter-rater agreement was excellent for pancreatic head (intraclass correlation coefficient (ICC): 0.837) and good for pancreatic neck, body and tail (ICC: 0.646, 0.632 and 0.678, respectively). We also defined the mean ADC values for three age groups. There was significant difference in the mean ADC value of the head and body by both the vendor and age group (p < 0.05). The mean ADC values and mean ranks of the Signa HDxt were significantly higher and the frequencies were lower than those of the MAGNETOM Symphony at all locations (p < 0.001). Conclusion: The thickness of the pancreatic head is more reliable than that at other locations. Pancreatic body and tail measurements are not as reliable as head or neck measurements due to discrepancies between published studies and low interobserver agreement. ADC values of the normal pancreas can be significantly different among vendors; therefore, ADC comparison on follow-up should be performed using same MRI machine. [ABSTRACT FROM AUTHOR]

Simple Summary: The dog is considered an animal model for the study of several diseases that occur in humans since they present similar phenotypic development. Among them, we can highlight diabetes mellitus and pancreatitis, which are diseases that affect the endocrine and exocrine portion of the pancreas, respectively, and showing high prevalence, social cost, mortality, and morbidity in companion animals. This work aimed to highlight the importance of using the dog as a model for the study of changes in the pancreatic extracellular matrix when affected by diabetes mellitus and pancreatitis. The extracellular matrix performs several functions, such as physical support and regulation of cellular processes, being composed mainly of proteins, glycoproteins, glycosaminoglycans, and proteoglycans. It is noteworthy that there are no studies characterizing the healthy and diseased canine pancreatic extracellular matrix, as well as studies related to the matrix components involved in the progression of these diseases. It is known that most pathological pancreatic conditions induce extracellular matrix changes through a remodelling process, which has to be thoroughly studied to fully understand the pathogenesis of any pancreatic disease. Diabetes mellitus and pancreatitis are common pancreatic diseases in dogs, affecting the endocrine and exocrine portions of the organ. Dogs have a significant role in the history of research related to genetic diseases, being considered potential models for the study of human diseases. This review discusses the importance of using the extracellular matrix of the canine pancreas as a model for the study of diabetes mellitus and pancreatitis, in addition to focusing on the importance of using extracellular matrix in new regenerative techniques, such as decellularization and recellularization. Unlike humans, rabbits, mice, and pigs, there are no reports in the literature characterizing the healthy pancreatic extracellular matrix in dogs, in addition to the absence of studies related to matrix components that are involved in triggering diabetes melittus and pancreatitis. The extracellular matrix plays the role of physical support for the cells and allows the regulation of various cellular processes. In this context, it has already been demonstrated that physiologic and pathologic pancreatic changes lead to ECM remodeling, highlighting the importance of an in-depth study of the changes associated with pancreatic diseases. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is an acute inflammatory disease of the exocrine pancreas. The pathogenesis of AP is still unclear, and there is currently no specific treatment. A variety of immune cells infiltrate in AP, which may play an important role in the progression of the disease. In this study, for the first time, scRNA-Seq and Bulk RNA-Seq data were used to show the characteristics of immune cell infiltration in AP, and to explore the specific molecular markers of different cell types. The present study also investigated cell-to-cell communication networks using the CellChat package, and AP-specific gene signatures (Clic1, Sat1, Serpina3n, Atf3, Lcn2, Osmr, Ccl9, Hspb1, Anxa2, Krt8, Cd44, Cd9, Hsp90aa1, Tmsb10, Hmox1, Fxyd5, Plin2, Pnp) were identified through integrative analysis of multiple sequencing datasets. We also defined disease-specific associated genes in different cell types, revealing dynamic changes through cell trajectory and pseudo-time analysis using the Monocle2 package. The results showed that macrophages were significantly increased in acute pancreatitis, and the number of interactions and interaction weight/strength of the macrophages in AP were significantly higher than those in the controls. The activities of various signaling pathways were abnormally regulated such as apoptosis, oxidative stress, lysosome, autophagy, ferroptosis, and inflammatory responses signaling pathways. In conclusion, this study comprehensively depicted the immune microenvironment of AP, explored the interaction network between different cell types, and defined AP-specific gene signatures, providing many new directions for basic research in AP. [ABSTRACT FROM AUTHOR]

Background: Extra-pulmonary features sometimes occur in association with atypical bacterial pneumonia and include neurologic manifestations, diarrhea, rashes, altered liver enzymes, or kidney injury, among other conditions. Acute pancreatitis has been associated with atypical pneumonias since 1973. Methods: We performed a systematic review of the literature in the Excerpta Medica, National Library of Medicine, and Web of Science databases. We retained 27 reports published between 1973 and 2022 describing subjects with an otherwise unexplained pancreatitis temporally associated with an atypical pneumonia. Results: The reports included 33 subjects (19 males, and 14 females; 8 children and 25 adults) with acute pancreatitis temporally associated with atypical pneumonia caused by Mycoplasma pneumoniae (n = 18), Legionella species (n = 14), or Coxiella burnetii (n = 1). Approximately 90% of patients (n = 29) concurrently presented with respiratory and pancreatic diseases. No cases associated with Chlamydophila pneumoniae, Chlamydophila psittaci, or Francisella species were found. Conclusions: Acute pancreatitis has been associated with various infectious agents. The present review documents the association with atypical pneumonia induced by Mycoplasma pneumoniae, Legionella species, and Coxiella burnetii. [ABSTRACT FROM AUTHOR]

Objective: Fat accumulation in the liver and pancreas are clinical manifestations of metabolic syndrome associated with inflammation. It aimed to investigate the effects of the computed tomography (CT) estimated non-alcoholic fatty liver disease (NAFLD) and non-alcoholic fatty pancreas disease (NAFPD) on the development of acute pancreatitis in this study. Patients and methods: This retrospective and cross-sectional study consisted of 194 participants admitted to the hospital with an abdominal pain complaint and underwent an abdominal CT scan during the investigation of the differential diagnosis. Medical database records of patients were investigated. Groups were consisted of according to the presence of acute pancreatitis as study and control. Attenuation measurements of the liver and pancreas were determined according to abdominal CT. Results: A statistical significance was observed for the development of acute pancreatitis when patients with normoglycemia were compared to patients with prediabetes and diabetes. Percentages of NAFLD and NAFPD according to the median of CT attenuation difference between pancreas and spleen values were elevated in the study group. A logistic regression model revealed that prediabetes, type 2 diabetes, NAFLD, and NAFPD, according to median value, were risk factors for acute pancreatitis (p<0.001, =0.001, =0.02, and =0.022). Discussion: NAFLD and NAFPD, according to the median value of patients without pancreatitis, were determined as independent risk factors for the development of acute pancreatitis. [ABSTRACT FROM AUTHOR]

Background: Despite the well-established diagnostic and therapeutic applications of endoscopic ultrasound (EUS) in adults, data about its use in children are limited. In this study, we tried to assess the feasibility, safety, and clinical impact of EUS in pediatric patients. Methods: Data of pediatric patients (<18 years) referred for EUS over a 3-year period to the endoscopy units of four Egyptian tertiary centers were retrospectively analyzed. Significant impact was defined as a new diagnosis or treatment attributed to the EUS procedure. Results: Twenty-four diagnostic and five therapeutic EUS procedures were conducted in 29 children with a median age of 9 years. Indications for EUS included assessment of solid pancreatic mass (n = 3), pancreatic cyst (n = 2), suspected chronic pancreatitis (n = 9), pancreatic pseudocyst (PPC) (n = 5), recurrent hypoglycemia (n = 1), bile duct mass (n = 1), subepithelial lesion (esophageal, duodenal or anorectal) (n = 4), mediastinal mass (n = 1), pelvic mass (n = 3), and mass at splenic hilum (n = 1). Therapeutically, five patients underwent cystogastrostomy for symptomatic PPC with 100% technical and clinical success. EUS was able to diagnose 21 out of the other 24 patients. EUS-guided tissue acquisition was performed in 11 patients with definitive histopathological diagnosis in 10 patients (91%). There was no procedure-related major complication, while minor complications occurred in two cases (transient pain in one case, temporary fever, and vomiting in two cases). Conclusion: Standard linear EUS equipment and accessories can be used safely and effectively in selected pediatric patients for diagnostic and therapeutic purposes. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is a major, globally increasing gastrointestinal disease and a biliary origin is the most common cause. However, the effects of bile acids (BAs), given systemically, on the pancreas and on disease severity remains elusive. In this study, we have investigated the roles of different circulating BAs in animal models for AP to elucidate their impact on disease severity and the underlying pathomechanisms. BAs were incubated on isolated acini and AP was induced through repetitive injections of caerulein or L-arginine; pancreatic duct ligation (PDL); or combined biliopancreatic duct ligation (BPDL). Disease severity was assessed using biochemical and histological parameters. Serum cholecystokinin (CCK) concentrations were determined via enzyme immunoassay. The binding of the CCK1 receptor was measured using fluorescence-labeled CCK. In isolated acini, hydrophobic BAs mitigated the damaging effects of CCK. The same BAs further enhanced pancreatitis in L-arginine- and PDL-based pancreatitis, whereas they ameliorated pancreatic damage in the caerulein and BPDL models. Mechanistically, the binding affinity of the CCK1 receptor was significantly reduced by hydrophobic BAs. The hydrophobicity of BAs and the involvement of CCK seem to be relevant in the course of AP. Systemic BAs may affect the severity of AP by interfering with the CCK1 receptor. [ABSTRACT FROM AUTHOR]

Simple Summary: In a recent retrospective analysis, we evaluated the diagnostic value of repetitive early FAPI-PET-imaging with FAPI-02, FAPI-46 and FAPI-74 for malignant, inflammatory/reactive and degenerative pathologies in 24 cancer patients. Here, we apply a subgroup analysis to that dataset. Differential uptake behavior over time was observed in several subclasses of malignant lesions, inflammatory/reactive lesions and degenerative lesions. These differences over time were particularly manifested in the direct comparison between the uptakes associated with pancreatic carcinoma (stable or increasing over time) and inflammatory lesions of the pancreas (markedly decreasing over time). We conclude that multiple timepoint FAPI-PET/CT is a promising innovative imaging technique that provides additional imaging information compared to single timepoint imaging. Purpose: FAPI-PET is a promising imaging technique for various malignant as well as non-malignant pathologies. In a recent retrospective analysis, we evaluated the diagnostic value of repetitive early FAPI-PET-imaging with FAPI-02, FAPI-46 and FAPI-74 for malignant, inflammatory/reactive and degenerative pathologies. Here, we apply a subgroup analysis to that dataset and describe the tracer-wise uptake kinetic behavior of multiple types of FAPI-positive lesions, which are encountered frequently during clinical routine. Methods: A total of 24 cancer patients underwent whole-body FAPI-PET scans, and images were acquired at 10, 22, 34, 46 and 58 min after the administration of 150–250 MBq of 68Ga-FAPI tracer molecules (eight patients each regarding FAPI-02, FAPI-46 and FAPI-74). Standardized uptake values (SUVmax and SUVmean) of healthy tissues, cancer manifestations and non-malignant lesions were measured and target-to-background ratios (TBR) versus blood and fat were calculated for all acquisition timepoints. Results: Differential uptake behavior over time was observed in several subclasses of malignant lesions, inflammatory/reactive lesions and degenerative lesions. These differences over time were particularly manifested in the direct comparison between the uptakes associated with pancreatic carcinoma (stable or increasing over time) and inflammatory lesions of the pancreas (markedly decreasing over time). Furthermore, marked differences were found between the three tracer variants regarding their time-dependent uptake and TBRs within different subclasses of malignant, inflammatory/reactive and degenerative pathologies. Conclusion: Multiple timepoint FAPI-PET/CT is a promising innovative imaging technique that provides additional imaging information compared to single timepoint imaging. Differences in the kinetic behavior of malignant and benign pathologies can facilitate the interpretation of FAPI-positive lesions. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Increased intrapancreatic fat deposition (IPFD) has emerged as a harbinger of pancreatic cancer and chronic pancreatitis. Although it is well recognized that diseases of the exocrine pancreas often lie on a continuum (with acute pancreatitis preceding the development of chronic pancreatitis and/or pancreatic cancer), whether increased IPFD predisposes to acute pancreatitis is unknown. This study aimed to compare fat depositions in the pancreas (as well as the liver and skeletal muscle) between individuals who developed first attack of acute pancreatitis and healthy individuals. METHODS: This was a matched case-control study nested into population-based cohort. MRI on a single 3 T scanner was used to quantify intrapancreatic, liver, and skeletal muscle fat depositions using the same protocols in all study participants. Binary logistic regression with adjustment for body mass index and other possible confounders was performed. RESULTS: Fifty individuals with first attack of nonnecrotizing acute pancreatitis comprised the case group and 100 healthy individuals comprised the control group. A 1% increase in IPFD (but not the other fat depositions) was significantly associated with a more than 30% higher chance of developing first attack of acute pancreatitis, consistently in both the unadjusted (P = 0.004) and all adjusted models. Furthermore, a 1% increase in IPFD (but not the other fat depositions) was significantly associated with up to a 27% higher chance of developing first attack of acute pancreatitis in individuals with normotriglyceridemia, consistently in both the unadjusted (P = 0.030) and all adjusted models. DISCUSSION: Increased IPFD may predispose to the development of acute pancreatitis. This opens up opportunities for reducing the burden of acute pancreatitis by means of primary prevention. [ABSTRACT FROM AUTHOR]

In 1995, Yoshida et al. proposed first the concept of "autoimmune pancreatitis" (AIP). Since then, AIP has been accepted as a new pancreatic inflammatory disease and is now divided two subtypes. Type 1 AIP affected immunoglobulin G4 (IgG4) and implicates the pancreatic manifestation of IgG4-related disease, while type 2 is characterized by neutrophil infiltration and granulocytic epithelial lesions (GEL). Recent research has clarified the clinical and pathophysiological aspects of type 1 AIP, which is more than type 2 among the Japanese population. However, many details remain unclear about the pathogenesis and progression of this disease. In this review, we discuss the current knowledge and recent advances relating to type 1 AIP. [ABSTRACT FROM AUTHOR]

The article focuses on pancreatitis with inflammatory process that affects to the pancreatic gland, and may also compromise neighboring and distant tissues. It mentions various causes of pancreatitis and treat with drug such as paracetamol salicylates, cytotoxic drugs (L-asparginase), corticosteroids, immunosuppressants (azathioprine6-MP), thiazides, valproat. It also mentions tachycardia, agitation, confusion, oliguria, tachypnea, and hypotension.

Purpose: The role of endoscopic retrograde cholangiopancreatography (ERCP) in the management of hepatobiliary and pancreatic diseases in the pediatric population was not well defined until recently. Our aim was to determine the feasibility, outcomes, and safety of ERCP in a local pediatric population, particularly using standard adult endoscopes and accessories. Methods: This retrospective study was conducted at the National Hospital of Sri Lanka. Pediatric patients (aged <16 years) who underwent ERCP from January 2015 to December 2020 were included in the study. Data, including patient demographics, indications for the procedure, technical details, and associated complications, were collected from the internal database and patient records maintained at the hospital. Results: The study included 62 patients who underwent a total of 98 ERCP procedures. All the procedures were performed by adult gastroenterologists using standard adult endoscopes and accessories. The mean age was 11.01±3.47 years. Pancreatic diseases were the major indications for most of the procedures (n=81, 82.7%), with chronic pancreatitis being the most common. Seventeen procedures (17.3%) were carried out for biliary diseases. Overall cannulation and technical success rates were 87.8% and 85.7%, respectively. Stent placement was the most common therapeutic intervention (n=66; 67.4%). Post-ERCP pancreatitis was the most common complication, occurring in eight patients (8.2%). Conclusion: ERCP can be successfully and safely performed in pediatric populations using standard adult endoscopes and accessories with complications similar to those of adults. Adult ERCP services can be offered to most pediatric patients without additional costs of pediatric endoscopes and accessories. [ABSTRACT FROM AUTHOR]

Background: Pancreaticopleural fistula, an abnormal communication between the pancreas and the pleural cavity, is a rare complication of pancreatic disease in children and is mainly associated with acute pancreatitis, chronic pancreatitis, trauma or iatrogenicinjury. The present review presents the current available data concerning the pathogenesis, clinical features, diagnosis and management of this unusual but difficult clinical problem among children, in order to shed light on its pathologic manifestation and raise clinical suspicion. Methods: The review of the literature was performed through a PubMed search of pediatric original articles and case reports, using the key words "pancreaticopleural fistula", "pancreatitis", "pleural effusion", "pseudocyst" and "children". The literature search revealed 47 cases of pediatric patients with pancreaticopleural fistula. Results: Diagnosis is based on the patient's medical history, physical examination and imaging, while the cornerstone of diagnosis is the presence of high pleural effusion amylase levels. The management of this disorder includes conservative, endoscopic and surgical treatment options. If treated promptly and properly, this clinical entity could have a lower rate of complications. Conclusions: The incidence of pancreaticopleural fistula in children may be underestimated in the literature, due to a reduced degree of clinical suspicion. A more heightened awareness of this entity is needed to improve the quality of life in children that suffer from this condition, as early diagnosis is essential for effective treatment and improved outcome. [ABSTRACT FROM AUTHOR]

Pancreatitis is one of the most common inflammatory diseases of the pancreas caused by autodigestion induced by excessive premature protease activation. However, recognition of novel pathophysiological mechanisms remains a still challenge. Both genetic and environmental factors contribute to the pathogenesis of pancreatitis, and the gut microbiota is a potential source of an environmental effect. In recent years, several new frontiers in gut microbiota and genetic risk assessment research have emerged and improved the understanding of the disease. These investigations showed that the disease progression of pancreatitis could be regulated by the gut microbiome, either through a translocation influence or in a host immune response manner. Meanwhile, the onset of the disease is also associated with the heritage of a pathogenic mutation, and the disease progression could be modified by genetic risk factors. In this review, we focused on the recent advances in the role of gut microbiota in the pathogenesis of pancreatitis, and the genetic susceptibility in pancreatitis. [ABSTRACT FROM AUTHOR]

Pancreatic diseases, such as pancreatitis and pancreatic cancer, remain the most threatening gastrointestinal diseases with a high mortality due to atypical symptoms. MicroRNA plays crucial roles in regulating metastasis and cell proliferation of pancreatic cancer, constituting important biomarkers for the early diagnosis of pancreatic cancers. Herein, we develop a sensitive and simple exosomal miRNA detection method with only a dual-hairpin-probe. In detail, the dual-hairpin-probe is constructed through combination of two functional sections for both target miRNA identification and signal amplification. With only one probe, the method possesses the capability to avoid interferences from concentration changes of other probes, and exhibits a higher stability which is demonstrated through the obtained low coefficients of variation (CV) of 6.73%. With let-7a as detection target, the LOD of the established method is determined to be 243 aM, while maintaining a high discriminating capability towards let-7a homogenous miRNAs. [ABSTRACT FROM AUTHOR]

As a pluripotent cell, activated pancreatic stellate cells (PSCs) can differentiate into various pancreatic parenchymal cells and participate in the secretion of extracellular matrix and the repair of pancreatic damage. Additionally, PSCs characteristics allow them to contribute to pancreatic inflammation and carcinogenesis. Moreover, a detailed study of the pathogenesis of activated PSCs in pancreatic disease can offer promise for the development of innovative therapeutic strategies and improved patient prognoses. Therefore, the present study review aimed to examine the involvement of activated PSCs in pancreatic diseases and elucidate the underlying mechanisms to provide a viable therapeutic strategy for the management of pancreas-related diseases. [ABSTRACT FROM AUTHOR]

Intermediate between apoptosis and necrosis, necroptosis is a regulated caspase-independent programmed cell death that induces an inflammatory response and mediates cancer development. As our understanding improves, its role in the physiopathology of numerous diseases, including pancreatic diseases, has been reconsidered, and especially in pancreatitis and pancreatic cancer. However, the exact pathogenesis remains elusive, even though some studies have been conducted on these diseases. Its unique mechanisms of action in diseases are expected to bring prospects for the treatment of pancreatic diseases. Therefore, it is imperative to further explore its molecular mechanism in pancreatic diseases in order to identify novel therapeutic options. This article introduces recent related research on necroptosis and pancreatic diseases, explores necroptosis-related molecular pathways, and provides a theoretical foundation for new therapeutic targets for pancreatic diseases. [ABSTRACT FROM AUTHOR]

Common pancreatic diseases have caused significant economic and social burdens worldwide. The interstitial microenvironment is involved in and plays a crucial part in the occurrence and progression of pancreatic diseases. Innate lymphoid cells (ILCs), an innate population of immune cells which have only gradually entered our visual field in the last 10 years, play an important role in maintaining tissue homeostasis, regulating metabolism, and participating in regeneration and repair. Recent evidence indicates that ILCs in the pancreas, as well as in other tissues, are also key players in pancreatic disease and health. Herein, we examined the possible functions of different ILC subsets in common pancreatic diseases, including diabetes mellitus, pancreatitis and pancreatic cancer, and discussed the potential practical implications of the relevant findings for future further treatment of these pancreatic diseases. [ABSTRACT FROM AUTHOR]

Introduction: A variety of imaging techniques exists for the diagnosis of pancreatic disorders. None of the broadly applied diagnostic methods utilizes elasticity as an indicator of tissue damage. A well-known fact is that both chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDA) are associated with the development of prominent fibrosis (increased tissue stiffness). Purpose: To prospectively assess the accuracy of point shear wave elastography (pSWE) in differentiating between benign and malignant pancreatic diseases, establish a cut-off value for the diagnosis of PDA, and evaluate the influence of certain variables on the obtained results. Materials and methods: The present study included 78 patients who were admitted at the Department of Gastroenterology at the university hospital "Kaspela" between December 2017 and August 2021 for diagnosis and/or treatment of pancreatic disorders. Based on the clinical criteria, diagnostic imaging, and histological findings, patients were divided into the CP and PDA group. The ultrasound based pSWE technique was applied and shear wave velocity (SWV) was measured. The depth of region of interest (ROI) and successful measurement rate were also recorded. Results: The mean ± SD SWV values established through pSWE were 1.75 ± 0.34 m/s and 2.93 ± 0.91 m/s for the CP and PDA, respectively. With a cut-off value of 2.09 m/s, we calculated the sensitivity (Se), specificity (Sp), and accuracy for differentiating between CP and PDA of 89.47%, 91.20%, and 88.60%, respectively. Of the examined variables, BMI and depth of ROI in the CP group and sex in the PDA group showed a statistically significant influence on the obtained results. Conclusions: pSWE may be utilized as a differential diagnostic modality in patients with suspected CP or PDA. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty pancreas disease (NAFPD) is a common and at the same time not extensively examined pathological condition that is significantly associated with obesity, metabolic syndrome, and insulin resistance. These factors can lead to the development of critical pathogens such as type-2 diabetes mellitus (T2DM), atherosclerosis, acute pancreatitis, and pancreatic cancer. Until recently, the diagnosis of NAFPD was based on noninvasive medical imaging methods and visual evaluations of microscopic histological samples. The present study focuses on the quantification of steatosis prevalence in pancreatic biopsy specimens with varying degrees of NAFPD. All quantification results are extracted using a methodology consisting of digital image processing and transfer learning in pretrained convolutional neural networks for the detection of histological fat structures. The proposed method is applied to 20 digitized histological samples, producing an 0.08% mean fat quantification error thanks to an ensemble CNN voting system and 83.3% mean Dice fat segmentation similarity compared to the semi-quantitative estimates of specialist physicians. [ABSTRACT FROM AUTHOR]

Interventional endoscopy is now considered an effective minimally invasive treatment modality for the management of pancreatic diseases. It is important for the clinician to know the indications and contraindications as well as the timing of various endoscopic interventions. This will help in its safe and effective use and consequently decrease morbidity and mortality from various pancreatic diseases. This review will provide a broad overview of the indications, techniques, and outcomes of pancreatic endotherapy. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) can involve multiple organ systems, and pancreatic manifestations of IBD are not uncommon. The incidence of several pancreatic diseases is more frequent in patients with Crohn's disease and ulcerative colitis than in the general population. Pancreatic manifestations in IBD include a heterogeneous group of disorders and abnormalities ranging from mild, self-limited disorders to severe diseases. Asymptomatic elevation of amylase and/or lipase is common. The risk of acute pancreatitis in patients with IBD is increased due to the higher incidence of cholelithiasis and drug-induced pancreatitis in this population. Patients with IBD commonly have altered pancreatic histology and chronic pancreatic exocrine dysfunction. Diagnosing acute pancreatitis in patients with IBD is challenging. In this review, we discuss the manifestations and possible causes of pancreatic abnormalities in patients with IBD. [ABSTRACT FROM AUTHOR]

[Display omitted] • Compared with other acute inflammation, acute pancreatitis develops rapidly, causing severe damage to the body and even death. • Macrophages play a major role in the occurrence and development of acute pancreatitis. • Gastrodin, as an anti-inflammatory drug, can effectively alleviate the progression of inflammation. • p38/NF-κB, as a classical inflammatory pathway, is important in disease progression in acute pancreatitis. • Gastrodin ameliorates acute pancreatitis by modulating macrophage inflammation cascade via inhibition the p38/NF-κB pathway. Acute pancreatitis (AP) is a prevalent, destructive, non-infectious pancreatic inflammatory disease, which is usually accompanied with systemic manifestations and poor prognosis. Gastrodin (4-hydroxybenzyl alcohol 4-O-β-d-glucopyranoside) has ideal anti-inflammatory effects in various inflammatory diseases. However, its potential effects on AP had not been studied. In this study, serum biochemistry, H&E staining, immunohistochemistry, immunofluorescence, western blot, real-time quantitative PCR (RT-qPCR) were performed to investigate the effects of Gastrodin on caerulein-induced AP pancreatic acinar injury model in vivo and lipopolysaccharide (LPS) induced M1 phenotype macrophage model in vitro. Our results showed that Gastrodin treatment could significantly reduce the levels of serum amylase and serum lipase while improving pancreatic pathological morphology. Additionally, it decreased secretion of inflammatory cytokines and chemokines, and inhibited the levels of p-p38/p38, p-IκB/IκB as well as p-NF-κB p-p65/NF-κB p65. Overall our findings suggested that Gastrodin might be a promising therapeutic option for patients with AP by attenuating inflammation through inhibition of the p38/NF-κB pathway mediated macrophage cascade. [ABSTRACT FROM AUTHOR]

Severe acute pancreatitis (SAP) is an inflammatory disease of the pancreas with a high mortality rate. Macrophages play a crucial role in the pathogenesis of pancreatitis. Tectoridin (Tec) is a highly active isoflavone with anti-inflammatory pharmacological activity. However, the role of Tec in the SAP process is not known. The purpose of this study was to investigate the therapeutic effect and potential mechanism of Tec on SAP. To establish SAP mice by intraperitoneal injection of caerulein and Lipopolysaccharide (LPS), the role of Tec in the course of SAP was investigated based on histopathology, biochemical indicators of amylase and lipase and inflammatory factors. The relationship between Tec and macrophage polarization was verified by immunofluorescence, real-time quantitative PCR and Western blot analysis. We then further predicted the possible targets and signal pathways of action of Tec by network pharmacology and molecular docking, and validated them by in vivo and in vitro. In this study, we demonstrated that Tec significantly reduced pancreatic injury in SAP mice, and decreased serum levels of amylase and lipase. The immunofluorescence and Western blot analysis showed that Tec promoted macrophage M2 polarization. Network pharmacology and molecular docking predicted that Tec may target ERK2 for the treatment of SAP, and in vivo and in vitro experiments proved that Tec inhibited the ERK MAPK signal pathway. In summary, Tec can target ERK2, promote macrophage M2 polarization and attenuate pancreatic injury, Tec may be a potential drug for the treatment of SAP. [Display omitted] • Tectoridin ameliorated pancreatic injury and inflammation in SAP mice. • Tectoridin regulated macrophage polarization and promoted M2 macrophage polarization. • Tectoridin targeted ERK2 to inhibit ERK MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] Diseases of the pancreas include acute and chronic pancreatitis, exocrine pancreatic insufficiency, diabetes and pancreatic cancer. These pathologies can be difficult to treat due to the innate properties of the pancreas, its structure and localization. The need for effective targeting of the pancreatic tissue by means of nanoparticles delivering therapeutics is a major focus area covered and discussed in this review. Most common diseases of the pancreas do not have specific and direct medical treatment option, and existing treatment options are generally aimed at relieving symptoms. Diabetes has different treatment options for different subtypes based on insulin having stability problems and requiring injections reducing patient compliance. Pancreatic cancer progresses silently and can only be diagnosed in advanced stages. Therefore, survival rate of patients is very low. Gemcitabine and FOLFIRINOX treatment regimens, the most commonly used clinical standard treatments, are generally insufficient due to the chemoresistance that develops in cancer cells and also various side effects. Therefore new treatment options for pancreatic cancer are also under focus. Overcoming drug resistance and pancreatic targeting can be achieved with active and passive targeting methods, and a more effective and safer treatment regimen can be provided at lower drug doses. This review covers the current literature and clinical trials concerning pancreatic drug delivery systems in the nanoscale focusing on the challenges and opportunities provided by these smart delivery systems. [ABSTRACT FROM AUTHOR]

There is general acceptance that a diagnosis of acute pancreatitis requires two of the following three features: 1) epigastric or upper abdominal pain characteristic of acute pancreatitis, 2) serum amylase and/or lipase ≥3 times the upper limit of normal, and 3) characteristic findings of acute pancreatitis on abdominal images such as ultrasonography, computed tomography (CT) or magnetic resonance imaging. Other pancreatic diseases and acute abdomen have been ruled out before making a diagnosis of acute pancreatitis. Serum lipase may be more useful than serum amylase because serum lipase is thought to be more sensitive and specific than serum amylase in the diagnosis of acute pancreatitis. Contrast-enhanced CT scan is the best imaging technique to rule out the conditions that masquerade as acute pancreatitis, to diagnose the severity of acute pancreatitis, and to identify complications of pancreatitis. The etiology of acute pancreatitis should be made clear as soon as possible to decide treatment policy of acute pancreatitis or to prevent the recurrence of pancreatitis. The etiology of acute pancreatitis in an emergency situation should be assessed by clinical history, laboratory tests such as serum liver function tests, measurement of serum calcium and serum triglycerides and ultrasonography. A differentiation of gallstoneinduced acute pancreatitis should be given top priority in its etiologic diagnosis because early endoscopic retrograde cholangiopancreatography should be considered if a complication of cholangitis and a prolonged passage disorder of the biliary tract are suspected. [ABSTRACT FROM AUTHOR]

Interventional endoscopy is now considered an effective minimally invasive treatment modality for the management of pancreatic diseases. It is important for the clinician to know the indications and contraindications as well as the timing of various endoscopic interventions. This will help in its safe and effective use and consequently decrease morbidity and mortality from various pancreatic diseases. This review will provide a broad overview of the indications, techniques, and outcomes of pancreatic endotherapy. [ABSTRACT FROM AUTHOR]

Background: Pancreatitis accounts for more than $2.5 billion of healthcare costs and remains the most common gastrointestinal (GI) admission. Few contemporary studies have assessed temporal trends of incidence, complications, management, and outcomes for acute pancreatitis in hospitalized patients at the national level. Methods: We used data from one of the largest hospital-based databases available in the United States, the Healthcare Cost and Utilization Project's (HCUP) State Inpatient Database, from 10 states between 2008 and 2015. We included patients with a diagnosis of acute pancreatitis (ICD-9 CM 577.0). Patient- and hospital-level data were used to estimate incidence and inpatient mortality rates. Results: From 80,736,256 hospitalizations, 929,914 (1.15%) cases of acute pancreatitis were identified, 186,226 (20.2%) of which were caused by gallbladder disease). The median age was 53 years (interquartile range [IQR], 41-67) and 50.8% were men. In-hospital mortality was 2.5% and crude mortality rates declined from 2.9% to 2.0% over the study period. Admission year remained significant after adjusting for patient demographics and comorbidities (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.89-0.90; p < 0.001). Gallbladder disease was associated with decreased odds of mortality (OR, 0.60; 95% CI, 0.57-0.62). Median length of stay was four days (IQR, 2-7) and decreased over time. The rates of surgical and endoscopic interventions were highest in 2011 (peak incidence of 16.1% and 9.5%, respectively) and have been decreasing since. Surgical providers were, on average, more likely than medical providers to perform surgery in both those with and without gallbladder disease etiology (gallbladder disease OR, 7.11; 95% CI, 5.46-9.25; non-gallbladder disease OR, 20.50; 95% CI, 16.81-25.01), endoscopy (gallbladder disease OR, 1.22; 95% CI, 0.87-1.72; non-gallbladder disease OR, 1.60; 95% CI, 1.18-2.16), or both (gallbladder disease OR, 7.00; 95% CI, 5.22-9.37; non-gallbladder disease OR, 8.85; 95% CI, 5.61-13.96). Conclusions: The incidence of pancreatitis, from 2008 to 2015, has increased whereas inpatient mortality (i.e., case fatality) has decreased. Understanding temporal trends in outcomes and management along with provider, hospital, and regional variation can better identify areas for future research and collaboration in managing these patients. [ABSTRACT FROM AUTHOR]