Search Results (577)

Main pancreatic duct (MPD) dilatation may occur in both main-duct intraductal papillary mucinous neoplasm (MD-IPMN) and chronic pancreatitis (CP). In selected patients, MRI/MRCP, endoscopic ultrasonography (EUS), and contrast-enhanced EUS may remain inconclusive. Peroral pancreatoscopy (POPS) permits direct ductal inspection and targeted biopsy, but the available evidence is heterogeneous and does not establish diagnostic accuracy or clinical utility in the specific differential diagnosis of MD-IPMN versus CP. We performed a narrative review of POPS for suspected pancreatic duct neoplasia and report a retrospective, descriptive, single-center series of five highly selected patients evaluated between January 2023 and November 2024. The case series is presented only to illustrate a multidisciplinary diagnostic pathway; no estimates of accuracy, sensitivity, specificity, or clinical benefit were calculated. All five patients had MPD dilatation > 10 mm, imaging findings compatible with definite or possible chronic pancreatitis, and persistent concern for MD-IPMN after MRI/MRCP, EUS, and contrast-enhanced EUS. POPS-guided biopsies showed low-grade dysplasia in one patient and high-grade dysplasia in two patients. These three patients underwent surgery, and examination of the resection specimens confirmed the same dysplasia categories identified by POPS-guided biopsy. In the remaining two patients, POPS showed regular-appearing ductal epithelium with focal hyperemia, and targeted biopsies revealed nonspecific inflammatory changes. These patients were managed conservatively without surgery. As definitive surgical histopathology was not available, their final diagnostic status remained unconfirmed. Both patients underwent ongoing planned annual surveillance with MRI or EUS and serum CA 19-9 measurement to identify any morphological or biochemical changes. At the most recent follow-up, approximately 192 days (IQR, 116.5–205.5 days) after POPS, no significant changes had been observed. This small, selected series illustrates how POPS may contribute additional visual and histological information when conventional evaluation is discordant. It cannot demonstrate that POPS prevents missed lesions, excludes IPMN, reduces unnecessary surgery, or improves outcomes. Prospective multicenter studies with predefined referral criteria, blinded interpretation, complete reference standards, and long-term follow-up are needed. Full article

Primary hepatic neoplasms in dogs, while uncommon, are occasionally associated with severe hypoglycemia, although the underlying mechanism may be difficult to establish. A 7-year-old castrated male Maltese dog weighing 3.6 kg was referred for recurrent bilateral pelvic limb weakness, episodic collapse, and abdominal distension. Severe hypoglycemia was documented, with a blood glucose concentration of 26 mg/dL. Computed tomography revealed a large mass arising from the right lateral liver lobe, with no identifiable pancreatic mass or distant metastasis. The serum insulin concentration measured during hypoglycemia was low at 1.0 μU/mL, making insulinoma less likely. Glycemic control temporarily or partially improved during prednisolone treatment; however, severe hypoglycemia recurred after prednisolone discontinuation before surgery. The hepatic mass was surgically excised. Dextrose-containing intravenous fluids were maintained for 6 h postoperatively, and no recurrent clinically significant hypoglycemia was documented after their discontinuation. Histopathologic examination revealed a poorly differentiated neoplasm with mesenchymal morphology, occasional cytoplasmic vacuolation, and no unequivocal lipoblasts. The neoplastic cells showed diffuse vimentin immunoreactivity, weak cytoplasmic S-100 immunoreactivity in a subset of cells, and no immunoreactivity for smooth-muscle actin or hepatocyte paraffin 1. These findings raised the possibility of adipocytic differentiation but were insufficient to establish a specific tumor lineage; therefore, the lesion was classified as a primary hepatic neoplasm of uncertain histogenesis. At 247 days after surgery, the dog remained normoglycemic without supplemental glucose or glucocorticoid treatment, and no imaging evidence of local recurrence or distant metastasis was identified. The postoperative course supported an association between the hepatic neoplasm and hypoinsulinemic hypoglycemia. Non-islet-cell tumor hypoglycemia was suspected but remained unconfirmed because an insulin-like growth factor-mediated mechanism was not demonstrated. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy, highlighting the need for reproducible experimental systems that model pancreatic injury and subsequent neoplastic progression. Adult-onset genetically engineered models in which oncogenic Kras and mutant Trp53 are induced in the pancreas provide a relevant platform for studying PDAC pathogenesis, but efficient neoplastic progression often requires concomitant pancreatic injury. Cerulein-induced pancreatitis is widely used to provide an injury-associated inflammatory stimulus that promotes PDAC progression; however, repeated-injection regimens are labor-intensive and increase cumulative handling stress in animals. Here, we describe a dose-optimized, single-dose L-Lysine protocol designed to induce acute pancreatitis and characterize subsequent pancreatic neoplastic progression in adult-onset Kras/Trp53-driven mice. Tamoxifen-treated Ptf1a^CreER/+; Kras^LSL-G12D/+; Trp53^LSL-R172H/+; Rosa26-RFP mice received a single intraperitoneal injection of L-Lysine, followed by biochemical, histological, and immunohistochemical assessment of pancreatic injury and tumor development. A single 2.0 g/kg L-Lysine injection induced sublethal acute pancreatitis characterized by increased serum pancreatic enzymes, interstitial edema, inflammatory cell infiltration, acinar cell necrosis, and rapid mitochondrial alterations. During 3–6 months of follow-up, mice developed multifocal acinar-to-ductal metaplasia, PanIN lesions, invasive PDAC, and peritoneal dissemination. This protocol provides a simple, synchronized, and less labor-intensive model for studying pancreatic injury and subsequent neoplastic progression in adult-onset Kras/Trp53-driven mice. Full article

Elastography is an ultrasound-based technique that enables the non-invasive assessment of tissue stiffness. In endoscopic ultrasound (EUS), elastography was initially introduced as a strain-based method, providing qualitative or semi-quantitative information on tissue deformation. More recent technological developments have enabled the integration of shear-wave-based elastography into EUS platforms, including shear-wave measurement (SWM), point shear-wave elastography (pSWE), and two-dimensional shear-wave elastography (2D-SWE). Unlike strain elastography, shear-wave techniques provide quantitative estimates of tissue stiffness by measuring shear-wave velocity or a derived elastic modulus. This invited narrative review summarizes the technical principles, terminology, quality-control requirements, and current clinical evidence for EUS-guided shear-wave-based elastography in pancreatic and hepatobiliary diseases. Because much of the available EUS literature derives from EUS-SWM or point SWE rather than true 2D-SWE, acquisition mode is a central determinant when interpreting clinical evidence and clinical readiness. Current data suggest that EUS-guided shear-wave-based elastography is technically feasible and biologically plausible, but its clinical maturity remains indication-specific. Evidence is most encouraging in chronic pancreatitis, early chronic pancreatitis, autoimmune pancreatitis activity monitoring, and selected endo-hepatology settings, particularly liver fibrosis assessment in patients in whom transabdominal techniques may be suboptimal. In contrast, available evidence does not support EUS-guided shear-wave-based elastography as a standalone diagnostic test for differentiating solid pancreatic lesions, including pancreatic ductal adenocarcinoma, because absolute stiffness values often overlap among malignant lesions, inflammatory masses, and background parenchyma. Before routine clinical implementation, standardized acquisition protocols, disease-specific cut-offs, multicenter reproducibility data, and evidence of incremental clinical value beyond established diagnostic pathways are required. Full article

Background: Machine learning (ML) is increasingly applied in medicine, underscoring the need for transparent and clinically relevant models. In gastrointestinal oncology, most ML studies rely on raw imaging data, which limits clinical adoption due to poor interpretability and the difficulty of collecting high-quality, large-scale video and image datasets in routine practice. Endoscopic ultrasound (EUS) plays a central role in the evaluation of pancreatic cancer; however, structured EUS features remain underused in predictive modeling. Objective: To assess the performance and interpretability of ML models for diagnosing pancreatic ductal adenocarcinoma (PDAC) using routinely collected EUS variables. Methods: We conducted a retrospective multicenter study using data from two Italian hospitals (n = 641) for model training and internal validation and from a third hospital (n = 120) for external validation, collected from 2015 to 2023. Decision trees, random forests, naïve Bayes and other classifiers were developed and evaluated. Model performance was assessed in terms of discriminative ability, calibration, and selective prediction. Results: All models demonstrated high discriminative performance (AUC ≥ 0.90). Decision trees provided the most favorable balance between interpretability and accuracy (balanced accuracy = 0.87; sensitivity = 0.89). Calibration and selective prediction analyses confirmed the robustness of the models. Conclusions: These findings demonstrate the feasibility of implementing interpretable yet high-performing ML models for PDAC diagnosis in real-life endoscopic settings. Full article

Background: Liver cancers are a major cause of morbidity and mortality in patients where effective, non-invasive treatment options remain limited. Objective: Histotripsy is a non-invasive, non-thermal, image-guided focused ultrasound method of ablation that mechanically disrupts cells and offers a range of potential advantages over other ablation modalities. The lack of physiologically and anatomically relevant animal models of human liver cancer has significantly hindered biomedical device development, including histotripsy. Methods: To address these limitations, we developed a clinically relevant large animal orthotopic, dual-tumor model of human liver cancer and utilized these unique animals to evaluate the safety and efficacy of histotripsy. Here, we utilized immunocompromised pigs with genetic modifications in their IL-2RG and RAG2 genes and orthotopically engrafted human hepatocellular carcinoma (HepG2/C3A) and pancreatic adenocarcinoma (Panc-1) cells within the liver. The models were designed to recapitulate primary and metastatic liver tumor phenotypes. Results: Histotripsy enabled real-time visualization of the treatment by the formation of bubble clouds and accurate targeting of the lesions. Histological analysis confirmed the engraftment of tumor cells and the ablation of targeted tissue. Serum biomarkers demonstrated no significant differences in bilirubin, ALT, ALKP, or CK post-treatment, suggesting that histotripsy treatment was well tolerated with minimal hepatic dysfunction or hepatocellular injury. Conclusions: These findings establish a novel, clinically relevant porcine model of primary and metastatic liver tumors and demonstrate the safety and feasibility of using this model for evaluating histotripsy as a noninvasive modality for precise tumor ablation. Full article

Background/Objectives: Pancreatic metastases are uncommon, and local treatment is reserved for selected patients with limited disease. Surgery remains the standard option when feasible, but may be inappropriate in patients with small, multifocal, anatomically challenging, or medically high-risk lesions. This study evaluated endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) as an organ-preserving local treatment for pancreatic metastases. Methods: Consecutive adult patients undergoing EUS-RFA for histologically confirmed pancreatic metastases at a tertiary endoscopy center between February 2021 and December 2025 were included. All cases were discussed in a multidisciplinary setting. EUS-RFA was performed using a 19G internally cooled RFA needle under real-time EUS guidance. The primary endpoint was initial complete radiological response, defined as complete ablation on first follow-up imaging. Secondary endpoints included technical success, radiological response, repeat EUS-RFA, adverse events, follow-up, and survival. Results: Eleven patients were treated; the mean age was 72.4 ± 6.4 years, and 7/11 (63.6%) were women. Primary tumors included renal cell carcinoma in 7/11 (63.6%), breast cancer in 2/11 (18.2%), melanoma in 1/11 (9.1%), and colorectal cancer in 1/11 (9.1%). Median lesion size was 10.5 mm. Technical success was achieved in 11/11 patients (100%). Initial complete radiological response at first follow-up was observed in 10/11 patients (90.9%); the remaining patient achieved complete response after repeat EUS-RFA. Adverse events occurred in 3/11 patients (27.3%), all mild and conservatively managed. No bleeding, perforation, pancreatic duct stenosis, pancreatic collection, or procedure-related death occurred. Median follow-up was 338 days. Conclusions: EUS-RFA appears feasible and generally well tolerated in carefully selected patients with pancreatic metastases, particularly small, well-visualized lesions when surgery is not feasible or an organ-preserving strategy is preferred. Larger prospective multicenter studies are needed. Although formal subgroup comparisons were not possible in this small cohort, lesion size, anatomical location, and primary tumor biology are likely to influence technical difficulty, local response, and the need for staged or repeat treatment. Full article

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and early diagnosis is essential for improving patient outcomes. Conventional imaging modalities such as ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) have limitations in detecting small PDAC. Endoscopic ultrasonography (EUS) is useful for identifying small lesions; however, even small PDAC can be invasive and may metastasize, resulting in Stage IV disease. The most effective way to improve the prognosis of PDAC is to diagnose lesions confined to the ductal epithelium, such as high-grade pancreatic intraepithelial neoplasia (HG-PanIN) or carcinoma in situ (CIS). Identifying focal pancreatic parenchymal atrophy (FPPA) on CT or MRI may suggest the presence of HG-PanIN/CIS and prompt further evaluation using serial pancreatic juice aspiration cytologic examination (SPACE). Recognizing FPPA and performing SPACE enables the diagnosis of PDAC at Stage 0 (HG-PanIN/CIS), which can lead to improved prognosis. Full article

Obesity and type 2 diabetes mellitus (T2DM) represent pandemic metabolic illnesses hallmarked by defective pancreatic β-cell function and blunted insulin release. As a conserved small GTPase (guanosine triphosphatase), ADP-ribosylation factor 6 (ARF6) governs fundamental cellular events encompassing vesicle trafficking, cytoskeleton remodeling and lipid metabolic turnover. Emerging data confirm that ARF6 acts as a master rheostat of glucose-stimulated insulin secretion (GSIS) in β-cells through downstream cell division control protein 42/Ras-related C3 botulinum toxin substrate 1 (Cdc42/Rac1) cascades. Pathogenic ARF6 hyperactivation triggers a cascade of β-cell lesions: mitochondrial impairment, autophagic suppression and exacerbated inflammatory signaling, accelerating the progression of obesity and T2DM. First-line therapeutics ranging from GLP-1 (Glucagon-like peptide-1) receptor agonists and metformin to SGLT2 (Sodium-Glucose Cotransporter 2) inhibitors partially restore metabolic homeostasis by rectifying aberrant ARF6-dependent signaling axes. This review comprehensively delineates ARF6’s canonical cellular roles, mechanistic bridges connecting ARF6 to β-cell failure and metabolic deterioration, and functional crosstalk between ARF6 and established anti-metabolic pharmacotherapies. We further address unresolved research gaps and prospective translational avenues, offering actionable perspectives to advance ARF6 as a tractable therapeutic target for obesity and T2DM management. Full article

Gastrinoma is a rare neuroendocrine tumor in dogs that arises from functional pancreatic non-β cells and secretes excessive gastrin. Gastrinoma in dogs has a high metastasis rate at diagnosis, and curative treatment is often difficult. There are few reports describing the long-term outcomes of surgical treatment in dogs with gastrinoma, and no established method for monitoring disease progression has been reported. We report here the cases of two adult dogs with pancreatic gastrinoma treated with surgical resection. Pharmacological therapy using proton pump inhibitors was administered to control gastrointestinal symptoms caused by hypergastrinemia. Multiple surgeries were performed to reduce the volume of primary and metastatic gastrinoma lesions. Serial serum gastrin concentrations were used as an adjunctive monitoring marker during follow-up. Changes in serum gastrin concentrations were used to support decisions regarding further imaging. Additional surgery was performed based on serum gastrin concentrations, clinical signs, and diagnostic imaging findings. A total of four surgeries were performed in Case 1 and three surgeries in Case 2. Both dogs maintained well-controlled gastrointestinal symptoms and showed long-term survival. The changes in serum gastrin concentrations in these cases suggest that serial serum gastrin measurement may be useful for monitoring recurrence or tumor progression in canine gastrinoma. Full article

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is among the most clinically relevant and conceptually intricate precancerous lesions encountered in modern gastroenterology. First identified in the early 1980s as a “mucin-producing tumor,” IPMN has since undergone a profound redefinition: from an obscure and poorly classified entity to a well-established precursor of pancreatic ductal adenocarcinoma (PDAC), shaped by characteristic molecular alterations such as KRAS, GNAS, and RNF43 mutations. Over the past two decades, the reported incidence of IPMN has risen sharply, a trend largely attributable to the widespread use of high-resolution cross-sectional imaging rather than a genuine increase in disease prevalence. IPMNs are categorized anatomically into main-duct (MD-IPMN), branch-duct (BD-IPMN), and mixed-type forms and histologically into gastric, intestinal, pancreatobiliary, and oncocytic subtypes, each associated with distinct malignant potential and prognostic implications. International consensus guidelines (Sendai 2006; Fukuoka 2012; Fukuoka revision 2017; Kyoto 2024) have progressively refined strategies for risk stratification and surgical decision-making. Nevertheless, significant debate persists regarding optimal surveillance intervals, thresholds for resection, and the management of low-risk branch-duct lesions. This review offers a comprehensive and critically evaluated synthesis about IPMN, spanning its historical recognition, molecular pathogenesis, epidemiology, clinical manifestations, diagnostic evaluation, pathological features, differential diagnosis, surveillance paradigms, long-term complications, associated conditions, therapeutic options, and future directions. Particular attention is given to longstanding “myths” that have influenced clinical practice and to emerging “realities” grounded in contemporary molecular and clinical evidence. Our aim is to provide physicians with a clear and updated framework for navigating the complexities of IPMN management in current practice. Full article

Background and Objectives: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is an emerging minimally invasive therapeutic option for pancreatic and selected extra-pancreatic lesions. However, its clinical adoption is limited by heterogeneous indications, non-standardized techniques, and variable quality of evidence. This systematic review assessed the published literature on EUS-RFA and classified available evidence according to the Oxford Centre for Evidence-Based Medicine levels of evidence. Materials and Methods: A systematic search was performed to identify peer-reviewed studies reporting clinical or translational data on EUS-RFA. Studies were grouped by indication, including pancreatic insulinoma, non-functioning pancreatic neuroendocrine neoplasms, branch-duct intraductal papillary mucinous neoplasms and other pancreatic cystic neoplasms, pancreatic ductal adenocarcinoma, pancreatic metastases, adrenal adenoma, and miscellaneous indications. Each study was categorized according to Oxford level of evidence based on study design. Results: Thirty-seven records were included in the final evidence map, comprising 36 clinical studies classifiable according to Oxford levels of evidence and one translational record not classifiable as clinical therapeutic evidence. Among the 36 clinically classifiable studies, one provided Level 1b evidence, consisting of a randomized trial evaluating EUS-guided celiac ganglion RFA for pancreatic cancer-related pain palliation, and three provided Level 2b evidence, including non-randomized comparative cohorts in pancreatic insulinoma and unresectable pancreatic ductal adenocarcinoma. Most clinically classifiable studies were Level 4 evidence (32/36), mainly uncontrolled prospective or retrospective cohorts and case series. One preclinical/translational study was not classifiable within clinical therapeutic evidence levels. Pancreatic insulinoma was the most evidence-supported tumor-ablation indication, with comparative data suggesting efficacy comparable to surgery and a more favorable safety profile. For non-functioning pancreatic neuroendocrine neoplasms, branch-duct IPMN, renal cell carcinoma pancreatic metastases, and adrenal adenomas, available data suggest feasibility and encouraging short-term outcomes but remain predominantly non-comparative. In pancreatic ductal adenocarcinoma, EUS-RFA remains investigational as an adjunct to systemic therapy. Conclusions: EUS-RFA is a promising therapeutic platform, but evidence remains highly indication-dependent and dominated by low-level observational studies. Standardized protocols, indication-specific outcomes, prospective registries, and comparative trials are needed. Full article

Objective: Current therapeutic regimens for pancreatic neuroendocrine neoplasms (pNENs) remain limited and fail to yield notable improvements in overall survival. Therefore, the development of novel agents is of paramount importance. Bruton’s tyrosine kinase inhibitors (BTKis) have demonstrated promising therapeutic potential in solid tumors; however, ibrutinib, a classic BTKi, exhibits unsatisfactory clinical efficacy against pNENs. In this study, we synthesized a novel pyrrolopyrimidine-based BTKi, QY21, and aimed to investigate its inhibitory effects on pNEN cell proliferation both in vitro and vivo and identify the core signaling pathways mediating its suppressive effects on pNENs. Methods: CCK-8, EdU, and colony formation assays were conducted to assess the effect of QY21 on pNENs in vitro. Transcriptome sequencing, quantitative real-time PCR, Western blotting, and flow cytometry were employed to explore the mechanisms. A xenograft tumor model in nude mice was established for in vivo validation. Results: QY21 significantly suppressed pNENs proliferation in vitro. Compared with the control and ibrutinib groups, QY21 exhibited stronger tumor growth inhibition in vivo. Histopathological analysis revealed a decreased Ki-67 index in the QY21 group, with no significant organ-toxic lesions observed. Transcriptome sequencing identified ATF3 as the core mediator responsible for the anti-proliferative effect of QY21. ATF3 was poorly expressed in pNENs, while QY21 markedly upregulated ATF3 expression. Mechanistically, QY21 induced ferroptosis by elevating ATF3 levels. The knockdown of ATF3 or administration of ferrostatin-1 significantly attenuated the anti-proliferative capacity of QY21, accompanied by reduced accumulation of reactive oxygen species and lipid peroxidation. Conclusions: This study demonstrates that the novel BTKi QY21 suppresses pNENs proliferation by triggering ATF3-mediated ferroptosis, providing a potential preclinical strategy for pNENs. Full article

(1) Background: Pancreatic ductal adenocarcinoma remains one of the most lethal malignancies due to late diagnosis, aggressive tumor biology, and limited therapeutic options. Artificial intelligence has emerged as a promising tool to improve detection, risk stratification, and treatment planning. This study aims to review the current clinical applications of artificial intelligence in the management of pancreatic cancer and evaluate its translational potential. (2) Methods: A comprehensive literature search was conducted across major databases (PubMed/MEDLINE, Scopus, Web of science and Cochrane) for studies published between 2015 and 2026. Eligible studies included clinical investigations and systematic reviews reporting quantifiable outcomes related to diagnosis, staging, prognostication, and treatment response using artificial intelligence methods. (3) Results: A total of 24 studies were included, most of which were retrospective and utilized imaging, histopathology, and clinical datasets. Artificial intelligence demonstrated high diagnostic performance, particularly in imaging-based detection and lesion characterization, with several models achieving excellent accuracy. Applications in staging, surgical planning, and prognostication also showed promising results, although external validation and prospective data were limited. (4) Conclusions: Artificial intelligence has significant potential to enhance the management of pancreatic cancer, particularly as a decision-support tool. However, further prospective validation and integration into clinical workflows are required before widespread adoption. Full article

Background and Aims: Accurate pre-operative identification of high-risk intraductal papillary mucinous neoplasms (IPMNs) remains a major clinical challenge, particularly for branch-duct (BD) lesions where guideline-based criteria incompletely capture biologic aggressiveness. We investigated whether tumoral mucin expression identifies high-risk IPMN pathology (i.e., high-grade dysplasia or invasive carcinoma) and whether computed tomography (CT)-derived radiomic features can serve as non-invasive biomarkers to enhance pre-operative risk assessment beyond international consensus guidelines (ICG) criteria. Methods: Multiplex immunofluorescence quantified MUC1, MUC2, MUC5AC, and MUC6 expression in tissue microarrays from 101 surgically resected IPMNs classified as low-risk (low-grade dysplasia) or high-risk (high-grade dysplasia or invasive carcinoma). Associations were evaluated using Wilcoxon rank-sum tests, and their discriminatory capability evaluated using receiver operating characteristic curves. For mucins predictive of high-risk pathology, a CT-based ‘radiomic’ signature was developed. Incremental value beyond ICG criteria was evaluated using discrimination metrics and decision curve analysis. Results: Reduced MUC6 expression was significantly associated with high-risk pathology (p = 0.001) and had the highest discriminatory performance (AUC = 0.72). A CT-derived radiomic signature predictive of low MUC6 expression achieved an AUC of 0.75 and, when integrated with ICG high-risk stigmata (HRS), demonstrated improved discrimination and favorable decision-curve characteristics compared with HRS alone, including among BD-IPMNs. Conclusions: Loss of tumoral MUC6 expression is associated with high-risk IPMN pathology and may be approximated using CT-derived radiomic features, supporting the feasibility of non-invasive molecular phenotyping. These findings suggest that integration of molecular and imaging biomarkers with guideline-based criteria may enhance pre-operative IPMN risk stratification; however, prospective external validation in broader surveillance populations and multi-institutional cohorts is warranted prior to clinical implementation. Full article