Search Results (335)

Background/Objectives: The aim of this study was to determine whether extracellular volume (ECV) fraction as determined by contrast-enhanced computed tomography (CECT) can help distinguish between autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDAC). Methods: Participants comprised 101 patients, including 20 diagnosed with AIP (AIP group), 42 with histologically confirmed PDAC (PDAC group), and 39 without pancreatic disease (healthy group). Contrast enhancement (CE) was calculated as CT attenuation in Hounsfield units [HU] on equilibrium-phase CECT–CT attenuation on pre-contrast CT. The ECV fraction was calculated by measuring the region of interest within the pancreatic region and aorta on pre-contrast and equilibrium-phase CECT. CT measurements were compared among groups. CE and ECV fractions were also compared for diffuse (n = 12) and focal or segmental types (n = 8). Focal- or segmental-type AIP was defined as the involvement of one or two pancreas segments. Diagnostic efficacy was evaluated through receiver operating characteristic (ROC) analyses. Results: CE and ECV fractions differed significantly between the groups (p < 0.001 each). CE was significantly higher in the AIP group (56.8 ± 7.9 HU) than in the PDAC group (42.3 ± 17.0 HU, p < 0.001) or healthy group (32.2 ± 6.1 HU, p < 0.001). ECV fraction was significantly higher in the AIP group (47.2 ± 7.3%) than in the PDAC group (31.7 ± 12.0%, p < 0.001) or healthy group (27.5 ± 5.4%, p < 0.001). In the AIP group, no significant differences in CE (56.7 ± 8.2 HU vs. 56.9 ± 8.1 HU; p = 1.000) or ECV fraction (48.0 ± 5.6% vs. 46.6 ± 8.4%; p = 0.970) were seen between diffuse and focal or segmental types. Areas under the ROC curve for differentiating AIP from PDAC were 0.78 for CE and 0.86 for ECV fraction, showing no significant difference (p = 0.083). Conclusions: ECV fraction might be clinically useful in differentiating AIP from PDAC. Full article

Background: Boiling histotripsy (BH) uses high-amplitude, short-pulse focused ultrasound to disrupt tissue mechanically. Oncolytic virotherapy using reovirus has shown modest clinical benefit in pancreatic cancer patients. Here, reovirus and BH were used to treat pancreatic tumours, and their effects on the immune transcriptome of these tumours were characterised. Methods: Orthotopic syngeneic murine pancreatic KPC tumours grown in immune-competent subjects, were allocated to control, reovirus, BH and combined BH and reovirus treatment groups. Acoustic cavitation was monitored using a passive broadband cavitation sensor. Treatment effects were assessed histologically with hematoxylin and eosin staining. Single-cell multi-omics combining whole-transcriptome analysis with the expression of surface-expressed immune proteins was used to assess the effects of treatments on tumoural leukocytes. Results: Acoustic cavitation was detected in all subjects exposed to BH, causing cellular disruption in tumours 6 h after treatment. Distinct cell clusters were identified in the pancreatic tumours 24 h post-treatment. These included neutrophils and cytotoxic T cells overexpressing genes associated with an N2-like and an exhaustion phenotype, respectively. Reovirus decreased macrophages, and BH decreased regulatory T cells compared to controls. The combined treatments increased neutrophils and the ratio of various immune cells to Treg. All treatments overexpressed genes associated with an innate immune response, while ultrasound treatments downregulated genes associated with the transporter associated with antigen processing (TAP) complex. Conclusions: Our results show that the combined BH and reovirus treatments maximise the overexpression of genes associated with the innate immune response compared to that seen with each individual treatment, and illustrate the anti-immune phenotype of key immune cells in the pancreatic tumour microenvironment. Full article

Acute pancreatitis (AP) is among the most frequent gastroenterology emergencies, with hospital admission rates on the rise in recent decades. However, a specific treatment for this condition is still lacking. Mitochondrial damage induced by oxidative stress is regarded as the key event in the pathophysiology and initiation of cellular damage in AP. In the early stages of AP, the oxidant–antioxidant balance changes rapidly, and there are significant data regarding the reduced serum levels of antioxidants, with this event being correlated with the clinical severity of pancreatitis. Therefore, addressing oxidative stress could represent a potential therapeutic target in AP. In this comprehensive review, we aimed to provide an update on current evidence regarding clinical and experimental data on antioxidant use in AP, focusing on human studies investigating the effects of single and combined antioxidant supplementation. Although a multitude of animal studies demonstrated that antioxidant therapy has beneficial effects in experimental AP by reducing oxidative injury, inflammatory markers, and ameliorating histological outcomes, human trials showed predominantly conflicting results, with some studies suggesting benefit while others showed no effect, or even potential harm, when antioxidants were administered in high doses or in combination. Moreover, some antioxidants with beneficial results in experimental settings did not show the same efficacy when translated to human studies, which may be a consequence of either inappropriate dosage, route of administration and duration of therapy, or altered pharmacodynamics in vivo. In conclusion, oxidative stress plays a key role in the pathophysiology of AP by enhancing acinar cell injury, inflammation, and systemic complications. Future studies should be centered on optimized dosing strategies, early administration protocols, targeted patient selection, and delivery methods of proper pharmaceutical forms. Full article

Background: Assessing pancreatic ductal adenocarcinoma (PDAC) resectability after neoadjuvant therapy (NAT) remains a diagnostic challenge. Traditional computed tomography (CT) criteria often fail to distinguish viable tumor from fibrosis, necessitating a reassessment of imaging-based standards. Methods: A comprehensive literature review was conducted using PubMed, focusing on prospective and retrospective studies over the past 25 years that evaluated the role of CT and complementary imaging modalities (MRI, PET-CT) in predicting resectability post-NAT in non-metastatic PDAC. Studies with small sample sizes or case reports were excluded. Results: Across studies, conventional CT parameters—particularly >180° vascular encasement—showed a limited correlation with histologic invasion or surgical outcomes after NAT. Persistent vessel contact on CT often reflected fibrosis, rather than active tumor. Dynamic changes, such as regression in the tumor–vessel interface and vessel lumen restoration, correlated more accurately with R0 resection. Adjunct markers like CA 19-9 response and patient performance status further improved resectability prediction. Conclusions: CT-based resectability assessment after NAT should transition from static morphologic criteria to response-based interpretation. Multidisciplinary evaluation integrating radiologic, biochemical, and clinical findings is essential to guide surgical decision-making and improve patient outcomes. Full article

The treatment of type 1 diabetes through pancreatic islet transplantation faces significant limitations, including donor organ shortages and poor islet survival due to post-transplantation loss of extracellular matrix support and inadequate vascularization. Developing biocompatible scaffolds that mimic the native islet microenvironment could substantially improve transplantation outcomes. This study aimed to create and evaluate decellularized (DCL) matrices from porcine organs as potential platforms for islet transplantation. Porcine lung and pancreatic tissues were decellularized using four different protocols combining detergents (Triton X-100, SDS and SDC) with optimized incubation times. The resulting matrices were characterized through DNA quantification and histological staining (H&E and Van Gieson). Islet viability was assessed in vitro using Live/Dead staining after 3 and 7 days of culture on the matrices. In vivo biocompatibility was evaluated by implanting matrices into rat omentum or peritoneum, with histological analysis at 1-, 4-, and 8 weeks post-transplantation. Protocols 3 (for lung tissue) and 4 (for pancreas tissue) demonstrated optimal decellularization efficiency with residual DNA levels below 8%, while preserving the collagen and elastin networks. In vitro, islets cultured on decellularized lung matrix had maintained 95% viability by day 7, significantly higher than the controls (60%) and pancreatic matrix (83%). The omentum showed superior performance as an implantation site, exhibiting minimal inflammation and fibrosis compared to the peritoneum sites throughout the 8-week study period. These findings establish DCL as a promising scaffold for islet transplantation due to its superior preservation of ECM components and excellent support of islet viability. This work provides a significant step toward developing effective tissue-engineered therapies for diabetes treatment. Full article

Background and Objectives: Endoscopic ultrasonography (EUS)-guided fine-needle aspiration/biopsy (FNA/B) is widely used for solid pancreatic lesions; however, the optimal number of needle punctures required to achieve high diagnostic accuracy remains unclear. This study aimed to identify the ideal number of punctures required for solid pancreatic lesions using EUS-FNA/B. Methods: This single-center retrospective study included 598 patients who underwent EUS-FNA/B for solid pancreatic lesions. We analyzed the cumulative tissue acquisition rates and diagnostic accuracy rates for cytology and histology, and identified the factors associated with diagnostic accuracy using univariate and multivariate analyses. Rapid on-site cytological evaluation was performed in all cases. Results: Cumulative tissue acquisition rates were 95.6% and 92.5% for cytology and histology, respectively. The diagnostic accuracy for cytology increased from 72.6% in the first puncture to 78.8% in the second puncture (p = 0.0233). In contrast, the diagnostic accuracy of histology increased from 72.0% at the first puncture to 83.2% at the third puncture (p = 0.0412). Statistically significant differences were noted between the first and second punctures for cytology, and between the first, second, and third punctures for histology. Univariate and multivariate analyses were conducted to identify factors associated with diagnostic accuracy. In cytology, sex was identified as a significant contributing factor, whereas no independent predictors were found in histology. Conclusions: These findings suggest that two-needle punctures are optimal for cytology, and three-needle punctures are optimal for the histological diagnosis of solid pancreatic lesions using EUS-FNA/B. Full article

Background: Hypothermia, occurring when core temperature drops below 35 °C, can lead to death when the body’s heat loss exceeds its heat production. This study investigates two hypothermia-related deaths, exploring the utility of immunohistochemistry, specifically focusing on chromogranin A (CgA) as a potential diagnostic tool. The aim is to assess whether CgA expression in neuroendocrine tissues can be considered a reliable indicator of premortem stress response in fatal hypothermia cases. Case Presentation: In the first case, a 67-year-old man was found on a snowy road 24 h after his disappearance. The autopsy revealed cold-induced skin lesions, gastric hemorrhages, and cerebral and pulmonary edema. Positive CgA immunostaining was observed in the pancreatic islets and adrenal medulla. In the second case, a 49-year-old man was found dead in a wooded area with indications of suicide. Both cases were examined with attention to macroscopic findings and histological samples from major neuroendocrine organs. As in previous cases, CgA immunostaining was positive in the pancreatic islets and adrenal medulla. Staining intensity was moderate to strong, consistent with heightened neuroendocrine activity, supporting the hypothesis of systemic stress prior to death. Conclusions: Although CgA is a potentially valuable adjunct in hypothermia diagnosis, careful consideration of cadaveric preservation is emphasized, particularly when bodies are preserved before autopsy. Further studies with larger sample sizes are needed to confirm its diagnostic specificity and to distinguish true pathological patterns from postmortem artifacts. Full article

Background/Objectives: Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is a useful procedure for obtaining histological specimens. However, its utility in diagnosing autoimmune pancreatitis (AIP) has not yet been well studied. This study aimed to assess the diagnostic capability of EUS-FNB for AIP by comparing a 19-gauge Franseen needle (19FR) and a 22-gauge Franseen needle (22FR). Methods: This study included patients with a final diagnosis of AIP undergoing EUS-FNB for pancreatic lesions between January 2014 and February 2023. All patients underwent EUS-FNB with either 19FR or 22FR. Histological findings were evaluated according to the International Consensus Diagnostic Criteria (ICDC). The primary outcome was the diagnostic yield of Level 1 (≥3 ICDC items) or Level 2 (2 ICDC items). Results: The 19FR group included 31 patients, and the 22FR group included 36 patients. The Level 1 diagnostic rate was significantly higher in the 19FR group than in the 22FR group (90.3% vs. 61.1%, p = 0.010). No significant difference was observed in the Level 2 diagnostic rate. The 19FR group yielded significantly larger histological tissue samples than the 22FR group (median area: 9.19 mm²/session vs. 3.36 mm²/session, p < 0.001). The analysis demonstrated a positive correlation between tissue area and the number of histological diagnostic items obtained. Conclusions: EUS-FNB performed with the 19FR provided larger histological specimens and a higher histological diagnostic yield than the 22FR in the diagnosis of AIP. Obtaining a larger amount of tissue may facilitate a definitive diagnosis of AIP. Full article

Background/Objectives: Previous studies have shown that unformulated extracts of Passiflora ligularis leaves exhibit promising antidiabetic activity. This research aimed to demonstrate that formulating the extract into a self-emulsifying drug delivery system (PLE-SEDDS) enhanced its antidiabetic activity in a high-fat-diet/streptozotocin-induced diabetic mouse model. Methods: Blood glucose levels (BGLs) of diabetic mice were monitored during 21 days of oral administration of P. ligularis extract (PLE) and PLE-SEDDS. Control groups included metformin (positive control), vehicle, and SEDDS vehicle (negative controls). The animals underwent an oral glucose tolerance test (OGTT). The oxidative stress markers superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation quantified by malondialdehyde (MDA) levels were measured in the kidney, liver, and pancreas, complemented with histopathological analysis. Additionally, plasma lipid profile parameters were evaluated. Results: The PLE-SEDDS formulation demonstrated superior efficacy compared to the PLE extract in improving antidiabetic outcomes. Animals treated with PLE-SEDDS exhibited a minimal increase in blood glucose levels (11.5%) during the OGTT, compared to 27.4% with PLE and over 77% in the vehicle groups. PLE-SEDDS also showed greater enhancement of SOD and CAT activity, along with a more pronounced reduction in MDA levels, indicating stronger protection against oxidative stress. Histological analysis revealed significant preservation of pancreatic islets, and lipid profile analysis showed greater reductions in triglycerides, cholesterol, and LDL-C, alongside increased HDL-C levels. Conclusions: Altogether, these findings suggest that PLE-SEDDS exhibits superior antihyperglycemic, hypolipidemic, and antioxidant effects compared to the unformulated extract, making this novel formulation a promising option for treating type 2 diabetes mellitus. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy and is characterized by a very unfavorable prognosis. Rarely, patients may develop synchronous PDAC and another distinct primary pancreatic tumor, such as a pancreatic neuroendocrine tumor. This systematic review consolidates published case reports describing the presentation, imaging characteristics, management, and outcomes of patients with synchronous PDAC and other pancreatic malignancies. Methods: A comprehensive search of PubMed and Scopus identified 26 relevant case reports, with inclusion criteria focused on histologically confirmed synchronous pancreatic tumors and exclusion of metastatic disease. Results: The majority of patients present with two pancreatic lesions, often located in both the body and tail of the pancreas. Diagnostic imaging modalities, such as computed tomography and endoscopic ultrasound, reveal common findings. Tumor markers, particularly CA 19-9, are often elevated and aid in the diagnosis. Surgical approaches also vary according to tumor location and staging, with procedures ranging from Whipple surgery to total pancreatectomy. Chemotherapy is frequently employed postoperatively. Notably, lymph node involvement and larger tumor size are associated with poorer prognoses. Conclusions: In conclusion, these patients may present with a common or non-common clinical picture as well as laboratory and imaging findings, constituting an important and unique diagnostic and therapeutic challenge. Full article

Background: The pancreas develops from two independent buds that fuse to form the adult organ. Ontogeny has largely been neglected in pancreatic surgery. This study aims to demonstrate that the adult pancreas can still be divided into morphogenetic units based on its embryological compartments and connective tissue borders for potential therapeutic purposes. Methods: Ten donor bodies (four female, six male, aged 73–101 years) were used. Manual dissection, guided by the common bile duct to locate the embryological fusion plane, was performed to divide the pancreatic tissue. Immunohistochemical staining for pancreatic polypeptide differentiated the pancreatic tissue by embryological origin and was used to quantify dissection accuracy. Results: Landmark-guided dissection successfully separated the pancreas along a connective tissue plane in seven cases. The resulting compartments were distinctly divided along the dissection plane into an area rich in pancreatic polypeptide and an area with low accumulation. Two cases showed deviations from the dissection plane at the histological level. One case contained tumor tissue, interfering with the utilization of landmarks. Conclusions: Landmark-guided dissection of the pancreas based on its embryological fusion plane allows for reliable separation into morphogenetic compartments. Immunohistochemical staining for pancreatic polypeptide effectively differentiates tissue origins. This approach may enable more precise, differentiated pancreatic resections and tailored treatments, with potential for refinement in routine surgical practice. Approaching the pancreatic tissue with regard to its ontogenetic origin and its clearly distinguishable compartments might even enable tailored treatment beyond refined surgical procedures. Full article

The edible mushroom Coprinus comatus has a long history of use in metabolic diseases, which is increasingly documented by modern research. Due to its favorable nutritional composition, it was assumed that this mushroom could accelerate tissue recovery after acutely induced damage with subsequent disturbance of primarily carbohydrate metabolism. To test this hypothesis, the alloxan diabetes model was used, where experimental animals’ change in body weight and biochemical and histological indicators of recovery were monitored. Before performing the in vivo part, HPLC analysis of the C. comatus extract was carried out with subsequent in silico and in vitro tests. Comparing the animals treated with the mushroom in three different doses, no significant change in body weight was observed. Still, the change was also noticed in the lipid status and glycemia, with a dose-dependent beneficial effect. Morphometric analysis of pancreatic tissue stained by immuno-histochemical methods showed that long-term treatment with C. comatus leads to increased numerical density, nuclear volume, and absolute number of beta cells of the islets of Langerhans, which suffered severe damage after alloxan administration. Overall, C. comatus may contribute to faster tissue recovery after acute diabetic-relevant damage with chronic consequences. Full article

Retinoic acid receptor (RAR) γ expression is restricted during adult haematopoiesis to haematopoietic stem cells and their immediate offspring and is required for their maintenance. From zebrafish studies, RARγ is selectively expressed by stem cells and agonism in the absence of exogenous all-trans retinoic acid blocked stem cell development. Recent findings for the expression of RARγ have revealed an oncogenic role in acute myeloid leukaemia and cholangiocarcinoma and colorectal, head and neck, hepatocellular, ovarian, pancreatic, prostate, and renal cancer. Overexpression and agonism of RARγ enhanced cell proliferation for head and neck, hepatocellular, and prostate cancer. RARγ antagonism, pan-RAR antagonism, and RARγ downregulation led to cell growth which was often followed by cell death for acute myeloid leukaemia, astrocytoma, and cholangiocarcinoma as well as hepatocellular, primitive, neuroectodermal ovarian, and prostate cancer. Histological studies have associated high level RARγ expression with high-grade disease, metastasis, and a poor prognosis for cholangiocarcinoma and ovarian, pancreatic, and prostate cancer. RARγ is expressed by cancer stem cells and is a targetable drive of cancer cell growth and survival. Full article

Inflammation of the exocrine pancreas accompanies autoimmune diabetes in mouse models and humans. However, the relationship between inflammation in the exocrine and endocrine (islet) compartments has not been explored. To address this issue, we used a transgenic mouse model in which autoimmune diabetes is acutely induced after the transfer of islet beta cell-specific transgenic T cells. Histological analyses demonstrated that inflammation of the exocrine pancreas, which was initially mild, resulted in the transient but widespread disruption of acinar tissue. Islet inflammation preceded exacerbated exocrine pathology, progressed to T cell-induced islet damage/destruction and persisted when exocrine inflammation subsided. Heparanase-1 (HPSE-1), an endoglycosidase that degrades heparan sulfate in basement membranes (BMs), when preferentially expressed in recipient cells but not donor (HPSE-1-deficient (HPSE-KO)) T cells, played a critical role in both exocrine and islet inflammation. In this context, HPSE-1 facilitates the passage of autoimmune T cells across the sub-endothelial basement membrane (BM) of pancreatic blood vessels and initially into the exocrine tissue. Peak exocrine inflammation that preceded or accompanied the acute onset of diabetes and HPSE-1 potentially contributed to acinar damage. In contrast to inflammation, HPSE-1 expressed by donor T cells played a key role in the induction of diabetes by allowing autoimmune T cells to traverse peri-islet BMs in order to destroy insulin-producing beta cells. Overall, our findings suggest that major exocrine pancreas injury is not required for the initiation of autoimmune islet damage and is not essential at the time of diabetes onset. Full article

Acute pancreatitis (AP) an inflammatory condition caused by the premature activation of pancreatic proteases, leads to organ damage, systemic inflammation, and multi-organ failure. Severe acute pancreatitis (SAP) has high morbidity and mortality, affecting the liver, kidneys, and lungs. Autophagy maintains pancreatic homeostasis, with VMP1-mediated selective autophagy (zymophagy) preventing intracellular zymogen activation and acinar cell death. This study examines the protective role of VMP1 (Vacuole Membrane Protein 1)-induced autophagy using ElaI-VMP1 transgenic mice in a necrohemorrhagic SAP model (Hartwig’s model). ElaI-VMP1 mice show significantly reduced pancreatic injury, including lower necrosis, edema, and inflammation, compared to wild-type (WT) mice. Biochemical markers (lactate dehydrogenase-LDH-, amylase, and lipase) and histopathology confirm that VMP1 expression mitigates pancreatic damage. Increased zymophagy negatively correlates with acinar necrosis, reinforcing its protective role. Beyond the pancreas, ElaI-VMP1 mice exhibit preserved liver, kidney, and lung histology, indicating reduced systemic organ damage. The liver maintains normal architecture, kidneys show minimal tubular necrosis, and lung inflammation features are reduced compared to WT mice. Our results confirm that zymophagy functions as a protective pathophysiological mechanism against pancreatic and extrapancreatic tissue injury in SAP. Further studies on the mechanism of VMP1-mediated selective autophagy in AP are necessary to determine its relevance and possible modulation to prevent the severity of AP. Full article