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Background: The pancreas is a multifunctional organ involving both endocrine and exocrine functions which plays a crucial role in metabolism and digestion. The pancreas extends horizontally from the C-loop of the duodenum to the splenic hilum, located retroperitoneally at the first and second lumbar vertebrae. The uncinate process, a small hook-like projection from the head of the pancreas, may be absent in about 10% of individuals. The pancreas produces both exocrine secretions (pancreatic juice from acinar cells) and endocrine hormones (insulin and glucagon). This review aims to provide a comprehensive overview of the morphological, physiological, and histological aspects of human pancreas development. Conclusions: All professionals who treat problems of the human pancreas must possess thorough knowledge of its development, anatomy, histology, and physiology. [ABSTRACT FROM AUTHOR]

Quantitative abdominal magnetic resonance imaging (MRI) offers non-invasive, objective assessment of diseases in the liver, pancreas, and other organs and is increasingly being used in the pediatric population. Certain quantitative MRI techniques, such as liver proton density fat fraction (PDFF), R2* mapping, and MR elastography, are already in wide clinical use. Other techniques, such as liver T1 mapping and pancreas quantitative imaging methods, are emerging and show promise for enhancing diagnostic sensitivity and treatment monitoring. Quantitative imaging techniques have historically required a breath-hold, making them more difficult to implement in the pediatric population. However, technological advances, including free-breathing techniques and compressed sensing imaging, are making these techniques easier to implement. The purpose of this article is to review current liver and pancreas quantitative techniques and to provide a practical guide for implementing these techniques in pediatric practice. Future directions of liver and pancreas quantitative imaging will be briefly discussed. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is a complex disease driven by the immune system attacking the insulin-producing beta cells in the pancreas. Understanding the role of different T cell subpopulations in the development and progression of T1D is crucial. By employing flow cytometry to compare the characteristics of T cells, we can pinpoint potential indicators of treatment response or therapeutic inefficacy. Our study reveals elevated prolactin (PRL) levels in T1D patients, along with a decreased production of key cytokines. Additionally, PD1 appears to play a significant role in T1D. Notably, PRL levels correlate with an earlier disease onset and a specific T cell phenotype, hinting at the potential influence of PRL. These findings highlight the need for further research to identify promising cellular targets for more effective and tailored therapies. [ABSTRACT FROM AUTHOR]

Bi-hormonal islet endocrine cells have been proposed to represent an intermediate state of cellular transdifferentiation, enabling an increase in beta-cell mass in response to severe metabolic stress. Beta-cell plasticity and regenerative capacity are thought to decrease with age. We investigated the ontogeny of bi-hormonal islet endocrine cell populations throughout the human lifespan. Immunofluorescence microscopy was performed for insulin, glucagon, and somatostatin presence on paraffin-embedded sections of pancreata from 20 donors without diabetes aged between 11 days and 79 years of age. The mean proportional presence of glucagon-, insulin-, and somatostatin-immunoreactive cells within islets was 27.5%, 62.1%, and 12.1%, respectively. There was no change in the relative presence of alpha- or beta-cells with advancing age, but delta-cell presence showed a decline with age (R2 = 0.59, p < 0.001). The most abundant bi-hormonal cell phenotype observed co-stained for glucagon and insulin, representing 3.1 ± 0.3% of all islet cells. Glucagon/somatostatin and insulin/somatostatin bi-hormonal cells were also observed representing 2–3% abundance relative to islet cell number. Glucagon/insulin bi-hormonal cells increased with age (R2 = 0.30, p < 0.05) whilst insulin/somatostatin (R2 = 0.50, p < 0.01) and glucagon/somatostatin (R2 = 0.35, p < 0.05) cells decreased with age of donor. Findings show that bi-hormonal cells are present within human pancreatic islets throughout life, perhaps reflecting an ongoing potential for endocrine cell plasticity. [ABSTRACT FROM AUTHOR]

Given the increasing trend of cholecystectomy, it is imperative to reassess surgical and surveillance strategies in consideration of the potential long-term risks for digestive tract cancers. The objective of this study was to assess the risk of gastrointestinal (GI) and hepato-biliary-pancreatic (HBP) cancer incidence after cholecystectomy. The data for this cohort study was obtained from the National Health Insurance Service database in Korea. 715,872 patients who underwent cholecystectomy between 2004 and 2020 were compared to 1,431,728 individuals who did not underwent cholecystectomy after age, sex, and year of cholecystectomy was matched. The overall incidence rate ratio (IRR) for all GI and HBP cancers was 1.08 (95% C.I., 1.06–1.10). Specifically, the risk of diagnosis of extrahepatic bile duct cancer (IRR 1.92), intrahepatic bile duct cancer (1.78), hepatocellular carcinoma (1.22), and pancreatic cancer (1.13) was significantly increased in the cholecystectomy group. The highest IRR was observed within the 1–3 years following cholecystectomy. Subsequently, the risk of diagnosis gradually decreased and returned to a level comparable to that of the matched control group after 5 to 10 years. In conclusion, hepato-biliary-pancreatic cancer are frequently diagnosed subsequent to cholecystectomy. Too short period of post-cholecystectomy follow-up may hinder monitoring of hepato-biliary-pancreatic cancer occurrence. [ABSTRACT FROM AUTHOR]

Aim: To investigate the associations of high‐density lipoprotein (HDL) subfractions and apolipoprotein A‐I (apo A‐I) with fat in the pancreas. Methods: A total of 170 individuals were studied. All participants underwent magnetic resonance imaging on a single 3.0‐Tesla scanner to determine the presence/absence of fatty pancreas. HDL subfractions were measured using a commercially available lipoprotein subfractions testing system and classed as large, intermediate and small HDL. Both unadjusted and adjusted (accounting for demographics, anthropometrics, insulin resistance and other covariates) logistic regression models were built. Results: Individuals with fatty pancreas had significantly lower circulating levels of the large HDL class and apo A‐I. Every unit decrease in the large HDL class was associated with a 93% increase in the likelihood of fatty pancreas in the most adjusted model (P <.001). Every unit decrease in apo A‐I was associated with a 45% increase in the likelihood of fatty pancreas in the most adjusted model (P =.012). The intermediate and small HDL classes were not significantly associated with fatty pancreas. Conclusions: Fat in the pancreas is inversely associated with the circulating levels of large HDL particles and apo A‐I. Purposely designed studies are warranted to investigate the potential of fatty pancreas as an indicator of the risk of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

IPMN consensus guidelines make implicit judgments on what cancer risk level should prompt surgery. We used decision modeling to estimate this cancer risk threshold (CRT) for BD-IPMN patients. We created a decision model to compare quality-adjusted life years (QALYs) following surgery or surveillance for BD-IPMNs. We simulated treatment decisions for hypothetical patients, varying age, comorbidities and lesion location (pancreatic head/tail). The base case was a 60-year-old patient with mild comorbidities and pancreatic head IPMN. Probabilities, life expectancies, and utilities were incorporated from literature/public datasets. CRT was defined as the level of cancer risk at which the expected value of QALYs for surgery first exceeded that of surveillance. In the base case, surgery was preferred over surveillance, yielding 21.90 vs. 21.88 QALYs. The optimal CRT for a BD-IPMN patient depended on age, comorbidities, and location. CRT in the base case was 20 % and 3 % for an IPMN in the head and tail of the pancreas, respectively. Other drivers of preferred treatment were age and likelihood of postoperative mortality. For BD-IPMNs, the optimal CRT varies depending on patient age and risk of surgical complications. Personalized risk threshold values could guide treatment decisions and inform future treatment consensus guidelines. [ABSTRACT FROM AUTHOR]

The pancreas is a centrally located extraperitoneal organ within the anterior pararenal space. It is extensively connected to the extraperitoneal spaces by location and a network of mesenteries and ligaments. This provides interconnected avenues for vessels, lymphatics, and nerves to course through—as well as avenues for the spread of disease. The head of the pancreas results from the fusion of its ventral analog (anterior head) with its dorsal analog (posterior head). This differentiation provides two distinct pathways of spread of disease from the head of the pancreas. This communication will discuss the embryology, anatomy, and pathways of disease spread from the anterior and posterior pancreatic head. While any disease process can use these pathways, proven cases of adenocarcinoma of the pancreas are used for illustrations. [ABSTRACT FROM AUTHOR]

Large-scale retrospective studies allow for identification of disease trends, such as predisposing factors, typical clinical signs, and range of histologic lesions, which cannot be determined in individual case reports. Lesions of the endocrine pancreas of ferrets are extensively reported; however, there are no in-depth investigations of lesions in the exocrine pancreas. This retrospective analysis presents the histologic features, clinical signs, and concurrent diseases of lesions in the exocrine pancreas of ferrets. Seventy-seven lesions were reported and included acinar cell hyperplasia (n = 32), chronic pancreatitis (n = 16), acute pancreatitis (n = 13), acinar cell adenoma (n = 5), acinar cell carcinoma (n = 4), acinar cell atrophy (n = 3), presumptive acinar cell hypoplasia (n = 2), and lymphoma (n = 2). Our results demonstrate that acinar cell hyperplasia and chronic pancreatitis can both cause grossly visible pancreatic nodules. Hyperplasia was not associated with neoplastic transformation. In addition, acinar cell adenoma was slightly more common than carcinoma, which is contrary to most reports of neoplasia in ferrets. Our findings also suggest that acute pancreatitis can be a sequela to pancreatic biopsy and that there may be an association between chronic pancreatitis and diabetes mellitus in ferrets. Finally, zinc toxicosis was found to be an unlikely cause of pancreatitis in these ferrets based on zinc tissue concentration testing in a subset of cases. [ABSTRACT FROM AUTHOR]

Background: In recent years, the role of neurotrophins and their receptors in peripheral tissues has been of great interest. At a metabolic level, the brain-derived neurotrophic factor (BDNF) and its receptor trkB have been reported to participate in insulin secretion from the pancreas in response to increases in circulating blood glucose. Objetive: To determines the role of the BDNF-trkB pathway in insulin secretion and pancreatic morphology in rats fed a cafeteria-style diet for 16 weeks. Methods: For the study, male rats of the Wistar strain were divided into three groups as follows: (1) control group (standard diet), (2) CAF group (cafeteria-style diet) and (3) CAF group treated with ANA-12 (TrkB receptor antagonist). After 4 months of intervention, the glucose and insulin tolerance curves, serum insulin levels, body fat and hematoxylin-eosin staining pancreas were evaluated. Results: The results showed that the cafeteria-style diet induced an increase in the amount of body fat, alterations in the glucose tolerance curve, increased insulin circulation levels, increased HOMA indices and increased pancreatic islet size. The antagonism of the trkB receptor in the rats fed a cafeteria-style diet enhanced some effects such as the accumulation of body fat and insulin secretion and induced a greater increase in the pancreas islet size. Conclusions: Under conditions of cafeteria-style diet-induced obesity, the antagonism of the BDNF-trkB pathway had no enhanced effect on the increase in insulin secretion or pancreatic islet size. [ABSTRACT FROM AUTHOR]

The molecular HLA epitope mismatch is an advanced measure for developing de novo donor-specific antibodies (dnDSA) after kidney transplantation. Its relevance in simultaneous pancreas/kidney transplant recipients (SPKTRs) remains unclear. We investigated dnDSA development in 72 SPKTRs and 383 kidney transplant recipients (KTRs) and used the Predicted Indirectly Recognizable HLA-Epitopes (PIRCHE-II) algorithm to calculate the mismatch load of HLA-derived epitopes in total, per HLA-class, and per HLA-locus. At 1 year post-transplant, SPKTRs exhibited an increased dnDSA incidence (11.2% vs. 3.1%, p = 0.011); but not at 10 years post-transplant. In SPKTRs, preformed DSA (HR 2.872, p = 0.039) and younger donor age (HR 0.943, p = 0.017) were independent risk factors for developing dnDSA. PIRCHE-II scores for HLA-DQ correlated with dnDSA development upon univariate analysis (p = 0.044). Among 455 KTRs/SPKTRs, multivariate analysis identified PIRCHE-II scores for HLA-DQ (HR 1.023, p = 0.025) and ciclosporine use (HR 2.440, p = 0.001) as independent predictors of dnDSA development. Simultaneous pancreas/kidney transplantation (SPK) was an independent risk factor in case of preformed DSA only (HR 2.782, p = 0.037). High PIRCHE-II scores for HLA-DQ are crucial for dnDSA development in both SPKTRs and KTRs. The lack of an independent association of total PIRCHE-II scores urges caution in implementing it in post-transplantation risk assessment. [ABSTRACT FROM AUTHOR]

Background: Meglumine antimoniate is used to treat canine leishmaniosis. In humans, it has been associated with pancreatitis. Although a few case reports have described acute pancreatitis secondary to antimonial treatment in dogs, some studies have concluded that pancreatitis is not an adverse effect of this medication. The objective was to evaluate whether treatment with meglumine antimoniate could induce pancreatitis in dogs with leishmaniosis, on the basis of clinical signs, canine serum specific quantitative pancreatic lipase immunoreactivity (cPLI) concentration, and ultrasonographic abnormalities. Methods: A prospective, observational, longitudinal, and multicentric study was conducted from April 2021 through February 2023. Results: A total of 33 dogs with leishmaniosis were included and classified into LeishVet clinical stages; 13 (39.4%) were included in stage II, 11 (33.3%) in stage III, and 9 in stage IV (27.3%). and 14 (42.4%) developed pancreatitis, 10 during treatment with meglumine antimoniate, and 4 at the end of the treatment. Advanced LeishVet clinical stage was statistically associated with development of pancreatitis. In addition, nine dogs received prednisone at the beginning of treatment, but it was not statistically associated with the prevention of pancreatitis. Conclusions: Meglumine antimoniate remains the first line leishmanicidal treatment option for canine leishmaniosis, but it appears to induce pancreatitis in a significant percentage of dogs. Monitoring serum cPLI levels and performing an abdominal ultrasound should be considered when pancreatitis-associated clinical signs are observed, or when there is a high suspicion of circulating immune complexes in dogs with advanced LeishVet clinical stage. [ABSTRACT FROM AUTHOR]

Simple Summary: Digestive cancers are still important contributors to the global burden of cancer in our society, and diet may play a role in their development. In our study, we observed an association between dairy products, especially fermented ones, and a lower risk of esophageal and stomach cancers, whereas high intake of sugary dairy desserts was linked to a higher risk of stomach cancer. Fermented dairy products, which contain beneficial compounds, such as probiotics, appear to offer a protective effect, particularly at higher levels of consumption. In contrast, high consumption of sugary dairy desserts, commonly rich in free sugars and unhealthy fats, was associated with a higher risk of stomach cancer. No significant association was found with milk consumption. These findings suggest that the risk of upper digestive tract cancers may be mitigated by consuming fermented dairy, while high intake of sugary dairy desserts could elevate this risk. Background/Objectives: This study explored the association between dairy products consumption (total and subgroups) and cancer of the esophagus, stomach, and pancreas within the PANESOES case–control study. Methods: Data from 1229 participants, including 774 incident cases of cancer and 455 controls matched by age, sex, and region, were analyzed. Dietary intake was assessed using a validated Food Frequency Questionnaire, categorizing dairy intake by total and subgroups (fermented dairy, sugary dairy desserts, and milk). Multinomial logistic regression was used to estimate relative risk ratios (RRRs), adjusting for confounders. Results: We found an inverse association between moderate dairy consumption (T2) and esophageal cancer (RRR T2 vs. T1 = 0.59 (95%CI: 0.37–0.96)). The highest tertile (T3) of fermented dairy was associated with a lower risk of esophageal (RRR T3 vs. T1 = 0.55 (0.33–0.90)) and stomach cancers (RRR T3 vs. T1 = 0.68 (0.47–0.97)). By contrast, the highest tertile of consumption of sugary dairy desserts was associated with a higher risk of stomach cancer (RRR T3 vs. T1 = 1.85 (1.30–2.64)). No association was found for milk. Conclusions: This study suggests that fermented dairy may reduce the risk of esophageal and stomach cancers, while sugary dairy desserts may increase the risk of stomach cancer. [ABSTRACT FROM AUTHOR]

Medical image segmentation is crucial for diagnostics and treatment planning, yet traditional methods often struggle with the variability of real-world clinical data. Deep learning models, like the Segment Anything Model (SAM), have been proposed as a powerful tool that helps to delimit regions using a prompt. This work proposes a methodology to improve the quality of the segmentation by integrating test-time augmentation (TTA) with the SAM for medical applications (MedSAM) by using random circular shifts, addressing challenges such as misalignments and imaging variability. The method generates several input variations during inference that are combined after, improving robustness and segmentation accuracy without requiring retraining. Evaluated across diverse computed tomography (CT) datasets, including Medical Segmentation Decathlon (MSD), KiTS, and COVID-19-20, the proposed method demonstrated consistent improvements in Dice Similarity Coefficient (DSC) and Normalized Surface Dice (NSD) metrics. The highest performances were 93.6% DSC and 97% NSD. Notably, it achieved superior boundary precision and surface alignment in complex regions like the pancreas and colon, outperforming baseline models, including MedSAM and DeepLabv3+. The approach is computationally feasible, leveraging a balance of augmentation intensity and segmentation accuracy. [ABSTRACT FROM AUTHOR]

Featured Application: Advanced deep learning methods can be applied to accurately measure pancreatic fat from multi-echo MR images. Pancreatic steatosis and metabolic-dysfunction-associated steatotic liver disease are characterised by fat accumulation in abdominal organs, but their correlation remains inconclusive. Recently proposed deep learning (DL) for proton density fat fraction (PDFF) estimation, which quantifies organ fat, has primarily been assessed for quantifying liver fat. This study aims to validate DL models for pancreatic PDFF quantification and compare pancreas and liver fat content. We evaluated three DL models—Non-Linear Variables Neural Network (NLV-Net), U-Net, and Multi-Decoder Water-Fat separation Network—against a reference PDFF measured using a graph-cut-based method. NLV-Net showed a strong correlation (Spearman rho) with the reference PDFF in the six-echo pancreatic head (slope: 1.02, rho: 0.95) and body (slope: 1.04, rho: 0.94) and a moderate correlation in the three-echo pancreatic head (slope: 0.44, rho: 0.40) and body (slope: 0.49, rho: 0.34). Weak correlations were found between liver and pancreatic body PDFF using graph cut in six-echo (slope: −0.041, rho: −0.12) and three-echo images (slope: 0.0014, rho: 0.073) and using NLV-Net in six-echo (slope: −0.053, rho: −0.12) and three-echo images (slope: −0.014, rho: −0.033). In conclusion, NLV-Net showed the best agreement with the reference for pancreatic fat quantification, and no correlation was found between liver and pancreas fat. [ABSTRACT FROM AUTHOR]

Green and Red LEDs increase insulin production, but their comparative effects on pancreatic and beta cell development are unclear. Zebrafish embryos were divided into three groups: Control (n = 60), Green (G) (n = 60), and Red (R) (n = 60), then irradiated for three days (14 hours/day) with 0.5 W/cm2 G (λpeak = 520 nm, 180 mA) and R (λpeak = 660 nm, 210 mA). At the end of 72 h, pancreatic and beta cells, circadian rhythm, and oxidative stress gene were analyzed using RT‐PCR. Malondialdehyde, nitric oxide, superoxide dismutase, and glutathione levels were also evaluated. In the Red group, pancreatic area increased by ~97.13% compared to the Control group and by approximately ~62.16% compared to the G group (both p < 0.0001), and no significant difference in beta cell area (p = 0.964). G group insulin expression increased 2.31‐fold compared to R group (p < 0.0001). Red LED treatment increased MDA levels (p < 0.001), oxidative stress (fth1b, nqo1) (p < 0.0001), and per1b during the photophase (p < 0.0001) compared to G group. R LED treatment increases oxidative stress and disrupts circadian rhythm, leading to reduced insulin secretion. The positive effects of G LED treatment have potential for metabolic syndrome, diabetes, and pancreatic diseases. [ABSTRACT FROM AUTHOR]

AbstractBackground: Infants of diabetic mothers (IDM) frequently show eosinophilic infiltrates around the pancreatic islets. We review 2 IDM, describe the pancreatic histology and review the literature. Case reports: Two term IDM died at 1 h and 43 days respectively. Both had eosinophilic infiltrates with frequent Charcot Leyden crystals surrounding the primary islets, had occasional eosinophils in these primary islets, but the infiltrate spared the acini and the intralobular islet tissue. There was no necrosis, fibrosis, or vasculitis. From the literature, this has been described as early as 28 weeks gestation, and occasionally was associated with peri-islet fibrosis. Conclusion: This infiltrate occurs antenatally, surrounds the primary islets, spares intralobular islet cells, persists past the neonatal period, and is not uniformly associated with islet or peri-islet injury. As eosinophils contribute to a variety of pancreatic inflammatory conditions, investigation may lead to further insights into the effect of maternal diabetes on the infant. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Intraductal papillary mucinous tumour (IPMN) of pancreas is increasingly recognized to have malignant potential. Fukuoka guidelines are commonly used to select patients with IPMN for resection due to high chance of malignancy, which includes high‐grade dysplasia (HGD) or invasive carcinoma (IC).A retrospective study on consecutive patients who have undergone pancreatectomy with IPMN as the final pathology was performed. Operative and survival outcomes were analysed. The positive predictive values (PPV) of high‐risk stigmata (HRS) and worrisome features (WF) of Fukuoka guidelines for HGD/IC were determined.Between August 2011 and September 2020, various types of pancreatectomy were performed for 36 patients with histologically proven IPMN. They included 26 pancreaticoduodenectomy, 7 distal pancreatectomy, 2 central pancreatectomy, and 1 total pancreatectomy. There were 30 branch duct type IPMN, 5 main duct type, and 1 mixed type. There was no 30‐day mortality. Overall complications and pancreatic fistula occurred in 44.4% and 5.6% of patients, respectively. Patients without HGD/IC had 100% survival at 5 years with no recurrent disease. There were 13 patients with HGD/IC, their 1‐, 3‐, 5‐year overall and disease‐free survival were 84.6%, 76.9%, 67.3% and 84.6%, 68.4%, 58.6%, respectively, both significantly shorter than non‐HGD/IC group (P = 0.002 and 0.001, respectively). The PPV of HRS and WF for HGD/IC were 33.3% and 23.5%, respectively. The combined PPV of HRS and WF for HGD/IC was 38.0%.Survival after pancreatectomy for IPMN was favourable, but was significantly worse in the presence of HGD/IC. Fukuoka guidelines were useful in predicting malignant IPMN. [ABSTRACT FROM AUTHOR]

Ewing sarcoma is a rare type of cancer that typically arises in the bones or soft tissues of children and young adults. However, Ewing sarcoma can also occur in other body parts, including the pancreas. Ewing sarcoma of the pancreas is rare and often affects children or young adults. We reported a 33-year-old male with no medical illness who presented with worsening epigastric pain and vomiting for one-week duration. CT scan of the abdomen showed an obstructive duodenal mass complicated with perforation. The biopsy of the duodenal mass showed sheets of small round blue cells with immunohistochemical features favouring Ewing sarcoma. Pancreatoduodenectomy procedure (Whipple resection) was performed, which revealed an ill-defined whitish solid tumour at the head of the pancreas measuring 80x50x65mm. Histologically, the tumour is composed of sheets of malignant cells displaying uniform small round to oval nuclei containing fine chromatin, inconspicuous nucleoli, scanty cytoplasm, and indistinct cell membrane. A few mitoses are seen (4/10HPF). Areas of tumour necrosis are observed. Scattered lymphovascular invasion is also present. The malignant cells are infiltrating into the duodenal mucosa. The malignant cells are diffuse and strongly positive towards CD99, FLI-1 and NK2.2 (Figure 3). A diagnosis of primary pancreatic Ewing sarcoma was made. [ABSTRACT FROM AUTHOR]

AbstractAcetamiprid is a neonicotinoid insecticide used against various insect pests. Serious concerns are emerging regarding their adverse effects on non-target organisms and organs. This study aimed to investigate the mechanistic toxic effect of oral administration of acetamiprid at 21.7 and 43.4 mg/kg body weight on the histological structure and pancreatic function of male Wistar rats and the potential effect of carnosine in mitigating this toxicity for 30 consecutive days. Thirty-six animals were divided into six groups: the control group received distilled water, the second group received 200 mg/kg body weight of carnosine, two groups received 21.7 and 43.4 mg/kg of acetamiprid, and two groups received 21.7 and 43.4 mg/kg + 200 kg/kg body weight of acetamiprid and carnosine, respectively. Acetamiprid caused a significant decrease in body weight (p < 0.001), pancreatic somatic index (p < 0.001), and amylase level (p ≤ 0.0001) and increased lipase level (p ≤ 0.0001), blood glucose level (p ≤ 0.0001), histological scores (p ≤ 0.01), and malondialdehyde level (0.01<p < 0.0001). Administration of carnosine led to a slight improvement in the increase of lipase (p ≤ 0.01) and the decrease of amylase (p ≤ 0.001) secretions and prevention of histopathological features induced by acetamiprid. Our results pointed out for the first time the toxic effect of acetamiprid and the preventive effect of carnosine on rat pancreatic structure and function. [ABSTRACT FROM AUTHOR]

Simple Summary: Mucinous epithelial pancreatic cystic lesions (PCLs) are premalignant lesions detectable through imaging techniques; however, distinguishing them from other PCLs with lower malignancy potential is challenging. Current methods like biochemical markers and genomic studies are not always reliable. Thermal liquid biopsy (TLB) is an innovative tool that analyzes the thermal profile of biological samples to detect disease-related alterations. In a retrospective study of 35 intracystic fluid samples obtained via fine needle aspiration, predictive models were developed using machine learning algorithms. Two classification models were created: TLB1, which differentiates mucinous from non-mucinous PCLs, demonstrating 92% sensitivity and 86% negative predictive value, and TLB2, which identifies benign and malignant mucinous lesions, achieving an area under the curve of 1.00. TLB shows promise in improving the differential diagnosis of PCLs and in detecting malignant transformations. Background/Objectives: Mucinous epithelial pancreatic cystic lesions (PCLs) are premalignant lesions readily detectable through imaging techniques such as multidetector computed tomography, magnetic resonance imaging, and endoscopic ultrasound (EUS). However, distinguishing these from other PCLs with lower or no malignant potential, and the early identification of those undergoing malignant transformation, remains a diagnostic challenge. Current methods, including biochemical markers in intracystic fluid (ICF) and genomic studies, offer some assistance but are not always reliable or accessible. Thermal liquid biopsy (TLB) is a novel diagnostic tool that examines the thermal profile (thermogram) of biological samples, reflecting their response to heat and thereby revealing characteristics of their overall composition or disease-induced alterations. Methods: In this retrospective study, a total of 35 ICF samples (49% mucinous) obtained via EUS-FNA (fine needle aspiration) were analyzed using TLB. Thermogram data were utilized to develop predictive models for differential diagnosis between mucinous and non-mucinous PCLs or malignancy detection through machine learning algorithms. Results: Two classification models were developed: TLB1 ("mucinous" vs. "non-mucinous" PCLs) and TLB2 ("benign mucinous" vs. "malignant mucinous" PCLs). The TLB1 model demonstrated a sensitivity of 92% and a negative predictive value of 86%, with an area under the curve (AUC) of 0.79 (0.59–0.99), indicating good discriminative ability between the two groups. The TLB2 model exhibited excellent predictive capability, with an AUC of 1.00. Conclusions: TLB analysis of PCLs is a promising tool that could significantly enhance the differential diagnosis of PCLs, enabling the efficient identification of mucinous lesions and even those undergoing malignant transformation. [ABSTRACT FROM AUTHOR]

Objective(s): Activating apoptosis and oxidative stress contributes to the pathogenesis of diabetes. Evening primrose oil (EPO) has been shown to regulate lipid profiles and hyperglycemia under metabolic conditions. This study aimed to examine the effect of EPO on miR-21 expression, oxidative stress, apoptosis, and histological changes in the pancreas of male rats with experimental diabetes induced by streptozotocin (STZ). Materials and Methods: Thirty-two Wistar rats were divided into four distinct groups: control, diabetic, diabetic + EPO, and EPO. EPO was administered orally at a dose of 500 mg/kg, and STZ was administered intraperitoneally at a dose of 35 mg/kg for 28 days. In the end, the effects of treatments were assessed by measuring expressions of miR-21 in the pancreas with real-time PCR, pancreatic histological and immunohistochemical changes examinations, and oxidative stress assessment. Results: In the diabetic group, miR-21 expression and the levels of caspase-3 and malondialdehyde (MDA) were increased compared to the control group, while insulin expression and superoxide dismutase activity (SOD) levels were decreased significantly. Treatment with EPO resulted in a reduction of miR-21 and caspase-3 expression, as well as MDA levels, and an increase in insulin expression and SOD levels compared to the diabetic group. Additionally, supplementation with EPO demonstrated the ability to restore pancreatic tissue features, serum insulin levels, and blood glucose fluctuations. Conclusion: Collectively, the protective impacts of EPO in diabetic rats may be linked to the inhibition of miR-21/caspase-3/oxidative stress pathway, leading to the restoration of pancreatic β-cell function and structure. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes mellitus (DM) has a millennia-long history, with early references dating back to ancient Egypt and India. However, it was not until the 20th century that the connection between diabetes and insulin was fully understood. The sequencing of insulin in the 1950s initiated the convergence of biotechnology and diabetes management, leading to the development of recombinant human insulin in 1982. This marked the start of peptide-based therapies in DM. Recombinant peptides for DM treatment: Numerous recombinant peptides have been developed since, starting with modified insulin molecules, with the aim of bettering DM management through fine-tuning the glycemic response to insulin. Peptide-based therapies in DM have expanded substantially beyond insulin to include agonists of Glucagon-like peptide-1 receptor and Glucose-dependent insulinotropic polypeptide receptor, glucagon receptor antagonists, and even peptides exerting multiple receptor agonist effects, for better metabolic control. Insulin pumps, continuous glucose monitoring, and automated insulin delivery systems: The development of modern delivery systems combined with real-time glucose monitoring has significantly advanced diabetes care. Insulin pumps evolved from early large devices to modern sensor-augmented pumps with automated shutoff features and hybrid closed-loop systems, requiring minimal user input. The second-generation systems have demonstrated superior outcomes, proving highly effective in diabetes management. Islet cell transplantation, organoids, and biological pancreas augmentation represent innovative approaches to diabetes management. Islet cell transplantation aims to restore insulin production by transplanting donor beta cells, though challenges persist regarding graft survival and the need for immunosuppression. Organoids are a promising platform for generating insulin-producing cells, although far from clinical use. Biological pancreas augmentation relies on therapies that promote beta-cell (re)generation, reduce stress, and induce immune tolerance. Further biotechnology-driven perspectives in DM will include metabolic control via biotechnology-enabled tools such as custom-designed insulin hybrid molecules, machine-learning algorithms to control peptide release, and engineering cells for optimal peptide production and secretion. [ABSTRACT FROM AUTHOR]

This experiment is to investigate whether interspecies differences exist in the effects of leucine (Leu) on digestive enzyme secretion in pancreatic tissues through in vitro. Five healthy Simmental cattle and Duroc × Landrace × Yorkshire growing-finishing pigs were selected, and pancreatic tissues were taken for culture after slaughter. Leu levels of 0, 2.62, 5.24, 10.48 mg/mL. Leu levels of 0, 5.24 mg/mL were selected to determine the expression of mRNA and proteins in the signaling pathways. The results showed that Leu increased the activity of digestive enzyme in cattle and pig, and there was an interaction was found on trypsin and chymotrypsin (P < 0.05). Leu had a significant effect on the mRNA (PKB, S6K1, 4E-BP1 and ATF4) and protein expression (PKB and 4E-BP1) and the phosphorylation (PKB, S6K1 and ATF4) levels (P < 0.05). Animal species had significant effects on the mRNA (PKB, S6K1 and ATF4) and protein (S6K1 and 4E-BP1) expression, and the phosphorylation (4E-BP1) levels (P < 0.05). There was an interaction between animal species and Leu on the expression of protein (PKB and S6K1) (P < 0.05). In summary, interspecies differences exist in the regulation of Leu on digestive enzyme secretion in pancreatic tissues in vitro of different animals. [ABSTRACT FROM AUTHOR]

Background: The impact method was used to make unilateral femoral comminuted fractures in tree shrews, which were then intravenously injected with lipopolysaccharide to create a traumatic systemic inflammatory response syndrome model. Methods: The treatment group was infused with tree shrew umbilical cord mesenchymal stem cells via the tail vein. After 10 days of treatment, 6 tree shrews were killed in the control, model and treatment groups and pancreatic tissue was collected for metabonomic analysis. Result: The 25 differential metabolites in the normal, model and stem cell treatment groups showed a trend of first decreasing and then increasing and 11 metabolites showed a trend of first increasing and then decreasing. These findings are in line with the recovery of the curative effect of the stem cell therapy model group. [ABSTRACT FROM AUTHOR]

Background: Phase‐contrast computed tomography (CT) using high‐brilliance, synchrotron‐generated x‐rays enable three‐dimensional (3D) visualization of microanatomical structures within biological specimens, offering exceptionally high‐contrast images of soft tissues. Traditional methods for phase‐contrast CT; however, necessitate a gap between the subject and the x‐ray camera, compromising spatial resolution due to penumbral blurring. Our newly developed technique, Superimposed Wavefront Imaging of Diffraction‐enhanced x‐rays (SWIDeX), leverages a Laue‐case Si angle analyzer affixed to a scintillator to convert x‐rays to visible light, capturing second‐order differential phase contrast images and effectively eliminating the distance to the x‐ray camera. This innovation achieves superior spatial resolution over conventional methods. Purpose: In this paper, the imaging principle and CT reconstruction algorithm based on SWIDeX are presented in detail and compared with conventional analyzer‐based imaging (ABI). It also shows the physical setup of SWIDeX that provides the resolution preserving second‐order differential images for reconstruction. We compare the spatial resolution and the sensitivity of SWIDeX to conventional ABI. Methods: To demonstrate high‐spatial resolution achievable by SWIDeX, the internal structures of four human tissues—ductal carcinoma in situ, normal stomach, normal pancreas, and intraductal papillary mucinous neoplasm of the pancreas—were visualized using an imaging system configured at the Photon Factory's BL14B beamline under the High Energy Accelerator Research Organization (KEK). Each tissue was thinly sliced after imaging, stained with hematoxylin and eosin (H&E) for conventional microscope‐based pathology. Results: A comparison of SWIDeX‐CT and pathological images visually demonstrates the effectiveness of SWIDeX‐CT for biological tissue imaging. SWIDeX could generate clearer 3D images than existing analyzer‐based phase‐contrast methods and accurately delineate tissue structures, as validated against histopathological images. Conclusions: SWIDeX can visualize important 3D structures in biological soft tissue with high spatial resolution and can be an important tool for providing information between the disparate scales of clinical and pathological imaging. [ABSTRACT FROM AUTHOR]

Purpose: Type 1 Diabetes (T1D) pathogenesis involves immune cells infiltrating pancreatic Islets of Langerhans, leading to T cell activation, beta cell destruction, and impaired insulin production. However, infiltration has a heterogenic nature that isn't described in detail, as not all islets are infiltrated. The aim of this study was to investigate if the observed heterogeneity is coupled to differences in immune and/or dysfunctional status of islets or exocrine cells, and if specific markers could elucidate mechanistic details of T1D pathogenesis. Procedures: The GeoMx platform was used to spatially quantify protein levels in pancreatic islets and exocrine tissue in Non-Obese Diabetic (NOD) mice. The protein panel included 17 immune activity markers and nine dysfunction markers. Immunohistochemical (IHC) staining and digital image analysis was used to analyze select marker proteins. Results: Use of the GeoMx platform to investigate T1D was shown to be possible, as Granzyme B protein levels were found to be lower in distal islet areas when compared to proximal areas. Smooth Muscle Actin protein levels were higher in exocrine areas proximal to immune-infiltrated islets, when compared to distally located exocrine areas. Findings from GeoMx were however not observed in IHC-stained sections. Conclusions: This study demonstrates that investigating T1D is possible with spatial proteomics, as the assays revealed presence of heterogenic islet areas in NOD mice, which may play a role in T1D progression and escape from immune recognition. This study highlights the potential of spatial technologies for elucidating T1D pathogenesis and future treatment strategies. [ABSTRACT FROM AUTHOR]

The current work attempted to examine the histological and immunohistochemical features of the pancreas in the southern white-breasted hedgehog (Erinaceus concolor). Five adult male individuals were used in this study. Utilizing hematoxylin and eosin as well as Masson's trichrome, staining was performed on paraffin sections of the pancreas. Immunofluorescent staining investigated the expression pattern of glucagon, insulin, somatostatin, neuropeptide Y (NY), and pancreatic polypeptide (PP). The exocrine pancreas comprised pyramidal and oval-shaped acini, exhibiting the clustering of zymogen droplets in the apical cytoplasm of acinar cells. The endocrine pancreas was distinguished as a large α islet of Langerhans and small β islets. Alpha cells were localized on the periphery of islets with an intensity of 20.6% ± 12.56. In comparison, Beta cells with 25.14% ± 5.89 intensity were gathered in the middle of the pancreatic islets. Delta cells exhibited 25.69% ± 5.13 intensity and were distributed through the islets. NY and PP cells were detected with 22.74% ± 3.25 and 16.80% ± 4.77 intensity, respectively. These cells showed prevalent distribution in the islets. In conclusion, it appears that although the pancreas of the southern white-breasted hedgehog is generally like other mammalian species, there are some species-specific features in density and dispersal of endocrine cells which can be attributed to the physiological purpose of the pancreas in this species. Future histophysiological investigations are still needed to explore the exact relationship between the histological organization of the pancreas and its function in that animal. [ABSTRACT FROM AUTHOR]

Pancreatic diseases, typically including pancreatic cancer, pancreatitis, and diabetes, pose enormous threats to people's lives and health. To date, therapeutics with high therapeutic efficacy and low side effects are still challenging. With the development of nanotechnology, nanomaterials have successfully been applied in pancretic disease treatment. Here, we first introduce the diversity of nanomaterials and the effects of their different physicochemical properties on pancreatic function. Following this, we analyze the potential of nanomaterials to enhance pancreatic targeting by overcoming the challenges of traditional delivery methods through surface modifications, structural adjustments, and optimized drug loading. Then, we introduce the application of structurally optimized nanomaterials to pancreatic-related diseases. For instance, on pancreatic cancer (as drug delivery platforms, for the promotion of radiation therapy, and as multifunctional tools), pancreatitis (as drug delivery systems, anti-inflammatory and anti-fibrotic agents), and diabetes (as insulin delivery carriers, for protecting pancreatic β cells, and for improving insulin resistance). Through analysis of the progress of current research, we summarize how nanomaterials can enhance treatment efficacy while minimizing side effects. Finally, we look forward to the prospects of nanomaterials in pancreatic disease treatment. [ABSTRACT FROM AUTHOR]

A 50‐year‐old male with a pancreatic tail tumor underwent distal pancreatectomy. At 14 and 27 months after the primary surgery, metachronous liver metastases were identified and partial hepatectomies were performed for each. Pathologic findings of the primary pancreatic tumor were heterogeneous, but they essentially categorized into two components based on their cytologic features: (i) clear cell component and (ii) epithelioid cell component. The metastatic hepatic tumor was entirely composed of the epithelioid cell component. SMARCB1 expression was lost by immunohistochemistry and heterozygous deletion of SMARCB1 was identified by fluorescence in situ hybridization for both the primary and metastatic tumors. Targeted DNA sequencing of a metastatic hepatic tumor sample was performed and SMARCB1 loss was identified. Based on the morphologic, immunohistochemical, and molecular analyzes, the present case was difficult to classify into any of the existing entities. SMARCB1 deficiency might play a key role in the tumorigenesis. [ABSTRACT FROM AUTHOR]

Purpose: Tumoral heterogeneity poses a challenge for personalized cancer treatments. Especially in metastasized cancer, it remains a major limitation for successful targeted therapy, often leading to drug resistance due to tumoral escape mechanisms. This work explores a non-invasive radiomics-based approach to capture textural heterogeneity in liver lesions and compare it between colorectal cancer (CRC) and pancreatic cancer (PDAC). Materials and methods: In this retrospective single-center study 73 subjects (42 CRC, 31 PDAC) with 1291 liver metastases (430 CRC, 861 PDAC) were segmented fully automated on contrast-enhanced CT images by a UNet for medical images. Radiomics features were extracted using the Python package Pyradiomics. The mean coefficient of variation (CV) was calculated patient-wise for each feature to quantify the heterogeneity. An unpaired t-test identified features with significant differences in feature variability between CRC and PDAC metastases. Results: In both colorectal and pancreatic liver metastases, interlesional heterogeneity in imaging can be observed using quantitative imaging features. 75 second-order features were extracted to compare the varying textural characteristics. In total, 18 radiomics features showed a significant difference (p < 0.05) in their expression between the two malignancies. Out of these, 16 features showed higher levels of variability within the cohort of pancreatic metastases, which, as illustrated in a radar plot, suggests greater textural heterogeneity for this entity. Conclusions: Radiomics has the potential to identify the interlesional heterogeneity of CT texture among individual liver metastases. In this proof-of-concept study for the quantification and comparison of imaging-related heterogeneity in liver metastases a variation in the extent of heterogeneity levels in CRC and PDAC liver metastases was shown. [ABSTRACT FROM AUTHOR]

Photon-counting CT has a completely different detector mechanism than conventional energy-integrating CT. In the photon-counting detector, X-rays are directly converted into electrons and received as electrical signals. Photon-counting CT provides virtual monochromatic images with a high contrast-to-noise ratio for abdominal CT imaging and may improve the ability to visualize small or low-contrast lesions. In addition, photon-counting CT may offer the possibility of reducing radiation dose. This review provides an overview of the actual clinical operation of photon-counting CT and its diagnostic utility in abdominal imaging. We also describe the clinical implications of photon-counting CT including imaging of hepatocellular carcinoma, liver metastases, hepatic steatosis, pancreatic cancer, intraductal mucinous neoplasm of the pancreas, and thrombus. [ABSTRACT FROM AUTHOR]

Ewing sarcomas are rare tumors arising mainly in the bones and the surrounding soft tissues. Primary extraosseous Ewing sarcomas have also been described in several other organs and locations other than bones, including the pancreas. These tumors have well-defined histological, immunohistochemical, and molecular characteristics. In this manuscript, we present a case of primary Ewing sarcoma of the pancreas in a 29-year-old patient, and we systematically review the literature on both primary and metastatic Ewing sarcomas of the pancreas, describing their clinicopathological characteristics. We also discuss the differential diagnosis and the treatment of this rare entity. [ABSTRACT FROM AUTHOR]

Background: Ischemia-reperfusion (I/R) injury is inevitable during the perioperative period. The pancreas is susceptible to I/R injury. Autophagy, a self-digestion process, is upregulated during I/R injury and strongly induced by hypoxia. This study aims to determine whether dexmedetomidine can decrease pancreatic ß-cell damage by regulating autophagy under hypoxia. Methods: INS-1 rat insulinoma cells were cultured in dexmedetomidine before being exposed to cobalt chloride (CoCl2)-induced hypoxia. Cell viability and the expression of autophagy-related proteins (light chain 3B [LC3B]-II, p62, and ATGs) were assessed. The expression of apoptosis-related proteins (BCL-2 and P-BAD) were also evaluated. Co-Cl2-treated INS-1 cells were pretreated with the autophagosome formation inhibitor, 3-methyladenine (3-MA), to compare its effects with those of dexmedetomidine. Bafilomycin-A1 (Baf-A1) that inhibits autophagosome degradation was used to confirm the changes in autophagosome formation induced by dexmedetomidine. Results: Dexmedetomidine attenuated the increased expression of autophagic proteins (LC3B-II, p62, and ATGs) and reversed the CoCl2-induced reduction in the proliferation of INS-1 cells after hypoxia. Dexmedetomidine also alleviated the decreased expression of the anti-apoptotic protein (BCL-2) and the increased expression of apoptotic protein (BAX). Dexmedetomidine reduces the activation of autophagy through inhibiting autophagosome formation, as confirmed by a decrease in LC3B-II/I ratio, a marker of autophagosome formation, in LC3B turnover assay combined with Baf-A1. Conclusions: Dexmedetomidine alleviates the degree of cellular damage in INS-1 cells against CoCl2-induced hypoxia by regulating autophagosome formation. These results provide a basis for further studies to confirm these effects in clinical practice. [ABSTRACT FROM AUTHOR]

In the last few decades, poor prognosis of pancreatic tumor has been an issue of concern in spite of the recent advancements in the different imaging modalities. Small size, similar attenuation to normal sized pancreas or concealed position of pancreas during CT scans are the factors that leads to failure in early diagnosis of pancreatic tumor. In this research, an organized framework is proposed for monitoring, classifying and diagnosing of pancreatic tumor. The suggested model integrates the technique of Deep Neural Network (DNN) and optimistic aspects of nature-inspired algorithms; this model aims to achieve a harmonious combination of both the techniques. The proposed model examines the medical images obtained from CT scans for the presence of pancreatic tumor using SSA-ML image segmentation on CT dataset. Evaluation of suggested model in comparison to other contemporary models IDLDMS, ODL, weighted KLM, Kernel-ELM, and ELM models is also performed in reference to sensitivity, specificity, accuracy and F1 score. The classification accuracy of our model is 99.44 % which reflects its supremacy over other recent models. [ABSTRACT FROM AUTHOR]

Background and Aims: The human gastrointestinal system hosts a rich and diverse microbial community, surpassing a staggering 10[ 14 ] bacteria, collectively harbouring more than 5,000,000 genes. The aim of this study is to carry out a systematic review of human studies in order to investigate the correlation between the gut microbiota and pancreatic disorders. Materials and Methods: To systematically compile relevant research between 2011 and 2022, a thorough exploration of the MEDLINE and EMBASE databases was executed. The initial search results, encompassing all identified studies, were meticulously scrutinised, including a comprehensive review of their reference lists to ensure the completeness of our search. Initially, our search strategy yielded a total of 114 items. Subsequent refinement involved the removal of 58 duplicate articles identified in both searches. Following a meticulous screening process involving title, abstract and keyword assessments, 36 studies progressed to the next phase of evaluation. However, this cohort underwent further scrutiny, leading to the exclusion of 11 studies categorised as reviews or case reports, 5 in languages other than English that have been published and 20 that did not investigate the microbiome. As a result, a focused set of 20 papers emerged for in-depth evaluation for eligibility. Results: The demographic profile of the patients revealed that nearly half were men, with an average age of 52 years (interquartile range of 44-56). The interquartile range further ranged from 45% to 52%, reflecting the distribution of ages within the group. Among the studies scrutinising acute pancreatitis, gallstones emerged as the predominant cause in 9 out of 15, while 7 studies focusing on chronic pancreatitis found no evidence of gallstones. Conclusion: This comprehensive, systematic investigation has furnished robust evidence substantiating the intricate connection between pancreatitis and the microbiota. [ABSTRACT FROM AUTHOR]

The Inonotus obliquus is a medicinal mushroom that grows on mature birch trees and is commonly used in traditional medicine for various ailments. The current study aimed to explore the hypoglycemic, hypolipidemic, and pancreatic protective effects of the water extract of Mongolian natural Inonotus obliquus on alloxan-induced diabetic mice. Alloxan monohydrate (200 mg/kg) was intraperitoneally single injected into C57BL/6 mice to induce diabetes. Alloxan-induced diabetic mice were orally given the water extract of inonotus obliquus (WEIO) at doses of 500 mg/kg and subcutaneously administered with insulatard 0.6 IU for 4 weeks. Subsequently, the levels of factors related to blood glucose, insulin and lipids were assessed. WEIO significantly restored body weight, reduced fasting blood glucose levels, improved glucose tolerance ability, and increased insulin levels compared to the control diabetic mice. WEIO also enhanced cholesterol transportation in the liver, correlated with increased HDL-C levels and decreased TC, TG and LDL-C levels. Histologic examinations revealed that WEIO alleviated alloxan-induced pancreatic tissue damage. Natural Mongolian I. Obliquus water extracts have an antihyperglycemic effect and enhance islet cell function in alloxan-induced diabetic mice. It is a good candidate for a hypoglycemic functional food or medicine. [ABSTRACT FROM AUTHOR]

Functional pancreatic neuroendocrine tumors (pNET) necessitate surgical resection. Enucleation is the preferred surgical method for well-differentiated pNETs that measure less than 2 cm in diameter, as it offers a greater likelihood of enhancing post-operative recovery and decreasing morbidity and mortality. Insulinomas are particularly suitable for enucleation when such a procedure is viable. However, enucleating tumors within the uncinate process of the pancreas, especially on its posterior aspect, can present substantial challenges. The accompanying video illustrates a robotic-assisted enucleation of an insulinoma in the uncinate process, performed on a 41-year-old male with recurrent hypoglycemia. This intervention led to the resolution of symptoms and incurred minimal post-operative morbidity. [ABSTRACT FROM AUTHOR]

Tumour evolution with acquisition of more aggressive disease characteristics is a hallmark of disseminated cancer. Metastatic pancreatic neuroendocrine tumours (PanNETs) in particular may progress from a low/intermediate to a high‐grade disease. The aim of this work was to understand the molecular mechanisms underlying metastatic progression as well as PanNET transformation from a low/intermediate to a high‐grade disease. We performed multi‐omics analysis (genome/exome sequencing, total RNA‐sequencing and methylation array) of 32 longitudinal samples from six patients with metastatic low/intermediate grade PanNET. The clonal composition of tumour lesions and underlying phylogeny of each patient were determined with bioinformatics analyses. Findings were validated in post‐alkylating chemotherapy samples from 24 patients with PanNET using targeted next generation sequencing. We validate the current PanNET evolutionary model with MEN1 inactivation that occurs very early in tumourigenesis. This was followed by pronounced genetic diversity on both spatial and temporal levels, with parallel and convergent tumour evolution involving the ATRX/DAXX and mechanistic target of the rapamycin (mTOR) pathways. Following alkylating chemotherapy treatment, some PanNETs developed mismatch repair deficiency and acquired a hypermutational phenotype. This was validated among 16 patients with PanNET who had high‐grade progression after alkylating chemotherapy, of whom eight had a tumour mutational burden >50 (50%). In comparison, among the eight patients who did not show high‐grade progression, 0 had a tumour mutational burden >50 (0%; odds ratio 'infinite', 95% confidence interval 1.8 to 'infinite', p = 0.02). Our findings contribute to broaden the understanding of metastatic/high‐grade PanNETs and suggests that therapy driven disease evolution is an important hallmark of this disease. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Aims: Acute heart failure (AHF) is associated with end‐organ dysfunction. The effect of AHF on the pancreas has not been studied. We aim to evaluate serum markers of pancreatic damage during hospitalization for AHF. Methods and results: In data from the Pragmatic Urinary Sodium‐based treatment algoritHm in Acute Heart Failure (PUSH‐AHF) study, amylase and lipase values were extracted from available serum samples at baseline, and at 24 and 72 h after hospitalization. The differences between pancreatic enzymes between timepoints were evaluated using the Friedman test. Associations with N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) were tested using linear regression analysis. The study population consisted of 274 patients. Mean age was 73 ± 11 years, and 117 (43%) were women. Mean left ventricular ejection fraction (LVEF) was 38 ± 14%; 53 (19%) patients had HF with a preserved LVEF (≥50%). At baseline, median amylase and lipase were within normal range (47 [33–63] U/L and 30 [21–44] U/L, respectively). Both enzymes significantly increased in the first 72 h (P‐value for trend <0.001); mean change was 9 ± 22 U/L for amylase, and 10 ± 22 U/L for lipase. Moreover, NT‐proBNP at baseline showed a positive correlation with mean change in pancreatic enzymes in 72 h (P = 0.02 for amylase and P = 0.006 for lipase). Conclusion: Patients admitted for AHF exhibited a significant increase in serum values of pancreatic enzymes in the first 72 h, suggesting that an episode of AHF affects the pancreatic tissue. This rise in pancreatic enzymes was associated with HF severity, as reflected by NT‐proBNP. [ABSTRACT FROM AUTHOR]

Organophosphorus, an insecticide used in agricultural and industrial settings, is the most common cause of poisoning in India. Organophosphorus is a nerve poison that causes irreversible inhibition of acetylcholinesterase, which leads to the accumulation of acetylcholine, resulting in excessive cholinergic stimulation of several organ systems. Several complications have been reported, but pancreatitis is quite rare and mainly due to ductal hypertension and injury to parenchyma, consequent to cholinergic hyperactivity in the pancreas. We present a case series of four cases where organophosphorus poisoning was suspected. Autopsy revealed that, in all four cases, the stomach walls were congested, pancreas showed gross haemorrhage over the surface and on cut sections, with other visceral organs showing generalised congestion. Later, after visceral and histopathological examination, all cases were confirmed as organophosphorus (dichlorvos) poisoning with haemorrhagic pancreatitis. Acute pancreatitis in organophosphorus poisoning usually has a subclinical course and gets masked by the systemic effects. Haemorrhagic pancreatitis sequela of acute pancreatitis is a rare and fatal complication of organophosphorus poisoning. [ABSTRACT FROM AUTHOR]

Accurate pancreas segmentation is essential for the diagnosis of pancreas disease, while it is still challenging due to the variable structure and small size of the pancreas. In this paper, we propose a Multi-scale Deformable U-Net with Cos-spatial and Channel Hybrid Transformer (MDHT-Net) for pancreas segmentation. To mitigate the ambiguity between the codec stages, the Cos-spatial and Channel Hybrid Transformer (CCHT) module is designed as a novel skip connection, enhancing the network's ability to perceive spatial information and reveal the inter-channel relationships within different layers' features. Furthermore, the CCHT efficiently aggregates multi-stage contextual information by improving the self-attention mechanism in two different manners, overcoming the limitation of computational complexity. In addition, to comprehensively understand deep semantic information, the Multi-scale Feature Adaptive-extraction (MFA) module is proposed to dynamically enhance the network's receptive field by integrating the pancreas characteristics of scale variations. The experimental results present that our proposed MDHT-Net achieves superior performance compared to other existing state-of-the-art methods on two public pancreas datasets, with the mean Dice coefficient of 91.07 ± 1.19 % for NIH and 91.52 ± 0.66 % for MSD, respectively. Given the effectiveness and advantages of our proposed MDHT-Net, it is expected to be a potential tool to assist clinicians in detecting pancreas disease and making reasonable treatment plans. [ABSTRACT FROM AUTHOR]

Background: Non‐invasive evaluation of phosphomonoesters (PMEs) and phosphodiesters (PDEs) by 31‐phosphorus MR spectroscopy (31P MRS) may have potential for early therapy (non‐)response assessment in cancer. However, 31P MRS has not yet been applied to investigate the human pancreas in vivo. Purpose: To assess the technical feasibility and repeatability of 31P MR spectroscopic imaging (MRSI) of the pancreas, compare 31P metabolite levels between pancreas and liver, and determine the feasibility of 31P MRSI in pancreatic cancer. Study Type: Prospective cohort study. Population: 10 healthy subjects (age 34 ± 12 years, four females) and one patient (73‐year‐old female) with pancreatic ductal adenocarcinoma. Field Strength/Sequence: 7‐T, 31P FID‐MRSI, 1H gradient‐echo MRI. Assessment: 31P FID‐MRSI of the abdomen (including the pancreas and liver) was performed with a nominal voxel size of 20 mm (isotropic). For repeatability measurements, healthy subjects were scanned twice on the same day. The patient was only scanned once. Test–retest 31P MRSI data of pancreas and liver voxels (segmented on 1H MRI) of healthy subjects were quantified by fitting in the time domain and signal amplitudes were normalized to γ‐adenosine triphosphate. In addition, the PME/PDE ratio was calculated. Metabolite levels were averaged over all voxels within the pancreas, right liver lobe and left liver lobe, respectively. Statistical Tests: Repeatability of test–retest data from healthy pancreas was assessed by paired t‐tests, Bland–Altman analyses, and calculation of the intrasubject coefficients of variation (CoVs). Significant differences between healthy pancreas and right and left liver lobes were assessed with a two‐way analysis of variance (ANOVA) for repeated measures. A P‐value <0.05 was considered statistically significant. Results: The intrasubject CoVs for PME, PDE, and PME/PDE in healthy pancreas were below 20%. Furthermore, PME and PME/PDE were significantly higher in pancreas compared to liver. In the patient with pancreatic cancer, qualitatively, elevated relative PME signals were observed in comparison with healthy pancreas. Data Conclusion: In vivo31P MRSI of the human healthy pancreas and in pancreatic cancer may be feasible at 7 T. Evidence Level: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Type 1 diabetes mellitus is an autoimmune condition characterized by the destruction of pancreatic β-cells, necessitating insulin therapy to prevent life-threatening complications such as diabetic ketoacidosis. Despite advancements in glucose monitoring and pharmacological treatments, managing this disease remains challenging, often leading to long-term complications and psychological burdens, including diabetes distress. Advanced treatment options, such as whole-pancreas transplantation and islet transplantation, aim to restore insulin production and improve glucose control in selected patients with diabetes. The risk of transplant rejection necessitates immunosuppressive therapy, which increases susceptibility to infections and other adverse effects. Additionally, surgical complications, including infection and bleeding, are significant concerns, particularly for whole-pancreas transplantation. Recently, stem cell-derived therapies for type 1 diabetes have emerged as a promising alternative, offering potential solutions to overcome the limitations of formerly established transplantation methods. The purpose of this scoping review was to: (1) summarize the current evidence on achieved insulin independence following various transplantation methods of insulin-producing cells in patients with type 1 diabetes; (2) compare insulin independence rates among whole-pancreas transplantation, islet cell transplantation, and stem cell transplantation; and (3) identify limitations, challenges and potential future directions associated with these techniques. We systematically searched three databases (PubMed, Scopus, and Web of Science) from inception to November 2024, focusing on English-language, peer-reviewed clinical studies. The search terms used were 'transplantation' AND 'type 1 diabetes' AND 'insulin independence'. Studies were included if they reported on achieved insulin independence, involved more than 10 patients with type 1 diabetes, and had a mean follow-up period of at least one year. Reviewers screened citations and extracted data on transplant type, study population size, follow-up duration, and insulin independence rates. We identified 1380 papers, and after removing duplicates, 705 papers remained for title and abstract screening. A total of 139 English-language papers were retrieved for full-text review, of which 48 studies were included in this review. The findings of this scoping review indicate a growing body of literature on transplantation therapy for type 1 diabetes. However, significant limitations and challenges, like insufficient rates of achieved insulin independence, risks related to immunosuppression, malignant diseases, and ethical issues remain with each of the established techniques, highlighting the need for innovative approaches such as stem cell-derived islet transplantation to promote β-cell regeneration and protection. [ABSTRACT FROM AUTHOR]

The objective of the current research was to characterize the correlation of Forkhead transcription factor and histopathologic findings of dogs’ pancreatic lesions. The study revealed a negative linear correlation (Correlation Coefficient 0.96) between lesions frequences and FOXO1 (lesions frequences move in opposing directions). Lesion frequences reduce as FOXO1 rises. Samples collected from the necropsy unit of veterinary teaching hospital at University of Mosul, college of veterinary medicine, to determine and confirm any histopathologic evidence of specific lesions these specimens histologically examined. In dogs, pancreatic lesions can range from mild inflammation (pancreatitis) to more severe conditions such as pancreatic cancer. Focusing on histopathological changes can help identify the correlation with FOXO1 expression. Various types of lesions were observed in the 17 pancreatic samples from dogs; however, none have been showed any evidence of neoplasia. Despite a lack of gross lesions, 14 samples (82.35%) exhibited microscopic pathological changes. Three samples (17.64%) revealed normal histology. In total, 12 types of microscopic lesions were identified. Among the 14 samples, degenerative changes, congestion, edema, coagulative and fat necrosis, as well as inflammation were detected in some samples. Multiple lesions, including fibrosis, hyperplasia, and atrophy, were observed in other samples. Additionally, cyst formations, metaplasia, and granulation tissue were determined. Dogs were randomly chosen, and all pancreatic samples were assessed through histopathological and immunohistochemical evaluation. This study concludes that lesions frequences move in opposing directions. Lesion frequences increase as FOX01 descend.

Abstract Lectins are produced in almost all life forms, can interact with targets (glycans) in a cross-kingdom manner and have served as valuable tools for studying glycobiology. Previously, a bacterial lectin, named Streptomyces hemagglutinin (SHA), was found to agglutinate human type B erythrocytes. However, the binding of SHA to mammalian cell types other than human erythrocytes has not been explored. To address this, we produced a recombinant fusion protein, with the mCherry reporter protein proceeding the SHA protein (referred to as mCherry-SHA), and performed co-immunofluorescence staining analysis. We focused on the normal pancreas in this study because glycans on pancreatic cells have been associated with initiation and progression of pancreatic cancer, a deadly disease. We found that only acinar, but not ductal or endocrine cells were stained positively with mCherry-SHA from embryonic day (E) 18.5 to 35 weeks old mice; in contrast, E12.5 and E15.5 pancreas display minimal mCherry-SHA binding. In adult humans, mCherry-SHA also targeted acinar cells specifically; however, only tissue from blood type B donors, but not type A or O donors, showed positivity. Together, these results demonstrate that SHA can bind to normal murine and human pancreatic acinar cells and that SHA-binding glycans are developmentally regulated.

To examine the hypoglycemic effects and myocardial protection of Sanghuangporus vaninii polysaccharide (SP) in T2DM rats, these effects were assessed in rats fed a high glucose and high fat diet combined with streptozotocin (STZ). The rats were randomly assigned to one of the following six groups: the diabetes mellitus (DM), metformin (MET), low-, medium-, and high-dose SP (SPL, SPM, and SPH), and control (CN) groups. Following 4 weeks of continuous intervention by gavage, the weights and multiple physiological and biochemical indicators of rats were measured and recorded, and performed pathological observations of the pancreatic and myocardial tissues of rats. Results revealed that SP at all assessed doses could reduce weight loss in T2DM rats compared to the DM group, significantly reduce fasting blood glucose and serum insulin levels, and improve glucose tolerance (P

ObjectiveTo analyze the associations between aging and fat deposition in the pancreas, liver, kidneys, and spleen. MethodsA total of 40 subjects were enrolled in the study. Fasting venous blood was collected and abdominal 3T MRI with the six-point Dixon-VIBE subsequence was performed. Fat fraction (FF) was quantified, and biochemical indexes related to glucose metabolism, lipid metabolism and liver and kidney functions were determined. Pearson correlation analysis was used to explore the correlations among variables. ResultsPancreatic fat fraction (PFF) had an independent positive correlation with age and a non-independently positive correlation with body mass index (BMI, P＜0.05); liver fat fraction (LFF) had an independently positive correlation with BMI and a non-independent association with age (P＜0.05); kidney fat fraction (KFF) had a non-independently positive correlations with both age and BMI (P＜0.05). There were positive correlations between PFF and LFF or KFF (P＜0.05); after adjusted PFF, there was no correlation between LFF and KFF. PFF was positively correlated with fasting C-peptide (FCP) and hemoglobin A1c (HbA1c, P＜0.05); LFF was positively correlated with fasting plasma insulin (FPI) and FCP, and was negatively correlated with high-density lipoprotein cholesterol (HDL-C, P＜0.05); KFF was positively correlated with fasting plasma glucose (FPG), triglyceride (TG) and was negatively correlated with HDL-C (P＜0.05). Spleen fat fraction (SFF) had no correlation with age, BMI and either metabolic parameters. ConclusionsAging significantly affects fat deposition in the pancreas, and may affect fat deposition in the liver and kidneys, with little effect on spleen metabolism.