Search Results (292)

Vitamin A plays an important role in multiple homeostatic functions such as vision, immunity, epithelial cell integrity and differentiation, cell signaling, pulmonary function, reproduction, growth, and development. Vitamin A deficiency was described in people with cystic fibrosis (pwCF) due to a multitude of causes, such as suboptimally managed exocrine pancreatic insufficiency, advanced cystic fibrosis-related liver disease (aCFLD), and a history of intestinal resection, and is generally rare in contemporary practice. Apart from true vitamin A deficiency, low vitamin A levels may also be noted in various inflammatory states, as vitamin A is a negative acute-phase reactant. In the current era of cystic fibrosis (CF) transmembrane-conductance regulator (CFTR)-directed therapies, there is a paradigm shift in vitamin A status, with deficiency statuses becoming rarer, and instead higher serum vitamin levels (in some cases, even in the hypervitaminosis range) are increasingly reported. People with aCFLD, renal insufficiency, post-lung transplantation, and pregnancy are prone to vitamin A toxicity. Hence, CF clinicians should be proactive in evaluating these abnormalities and proficient in managing both deficiency and toxicity, as both these conditions can be associated with adverse outcomes. In this review, we detailed the basics of vitamin A metabolism, manifestations of both vitamin A deficiency and excess, and their clinical implications in pwCF. 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

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

Benign biliary tumors and precursor neoplasms of the biliary tract are a heterogeneous group of uncommon neoplasms with significant clinical and diagnostic implications. Their importance lies in their variable malignant potential and morphological and molecular similarities to pancreatic neoplasms. The sixth edition of the World Health Organization Classification of Digestive System Tumours (WHO DST6), published online in 2026, introduced major revisions to the classification of these entities. According to WHO DST6, benign tumors and precursor neoplasms of the liver and intrahepatic bile ducts include bile duct adenoma, biliary adenofibroma, and mucinous cystic neoplasm, whereas those of the gallbladder and extrahepatic bile ducts include biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile ducts, intraductal tubulopapillary neoplasm of the bile ducts, intraductal oncocytic papillary neoplasm of the bile ducts, and mass-forming intracholecystic neoplasm. Despite these advances, their histological and molecular heterogeneity continues to pose significant diagnostic challenges, particularly in distinguishing them from malignant biliary tumors on limited biopsy specimens and in recognizing early invasive lesions. This review summarizes the clinicopathological and molecular features of benign biliary tumors and precursor neoplasms, emphasizing differential diagnosis and key updates introduced in WHO DST6. Full article

Background: Young children with Cystic Fibrosis (CwCF) are at risk of fat-soluble vitamin (FSV) deficiencies due to pancreatic insufficiency, despite pancreatic enzyme supplementation. CFTR modulator therapy such as elexacaftor/tezacaftor/ivacaftor (ETI) may improve pancreatic function, but its impact on FSV levels in this age group remains unclear. We evaluated changes in FSV serum levels in a cohort transitioning to ETI, taking a CF-specific, multivitamin formulation with beta-carotene as the primary source of vitamin A (DEKAs Plus Liquid, DPL). Methods: Retrospective data with paired analysis from 23 CwCF (2–5 years old) were analyzed. Serum FSV levels (D, E, A) and fecal elastase-1 (FE-1) were measured at baseline and 12 months post-ETI initiation. Daily FSV doses and covariates (FE-1, naive of CFTR modulators and ETI dose) were documented. Statistical analyses included Wilcoxon signed-rank tests and general linear models. Results: No significant changes were observed in serum FSV levels, while FSV dosing and formulation remained unchanged. Covariates did not influence serum level changes. Interestingly, ETI significantly improved FE-1 (p = 0.018), with 6/18 children achieving pancreatic sufficiency (FE-1 > 200 µg/g). Conclusions: In young CwCF initiating ETI, FSV levels were unchanged while pancreatic function improved. The use of provitamin A (beta-carotene) as in DPL resulted in no change in vitamin A levels and aligns with consensus guidance to prioritize provitamin A in ETI-treated children. Further validation in larger cohorts is warranted. Full article

Background: The clinical characteristics of pancreatic acinar cell carcinoma (ACC) remain poorly defined due to its rarity. This study aimed to evaluate the morphological features and clinical outcomes of pancreatic ACC. Method: This multicenter retrospective study analyzed clinical data from seven referral hospitals. Electronic medical records were comprehensively reviewed to extract patient data. Survival outcomes were calculated from the date of pathologic confirmation of ACC. Results: Of the 37 patients, 28 (75.7%) were male. The age distribution at diagnosis ranged widely from 12 to 86 years, with a median of 62.0 years; seven patients (18.9%) were aged under 50 years. Morphologically, 24 patients (64.9%) presented with solid masses, whereas four had cystic masses and four exhibited mixed solid and cystic components. Regarding tumor resectability, 19 patients (51.4%) had resectable disease, 7 (18.9%) were locally advanced, and 11 (29.7%) were metastatic. In terms of treatment, 22 patients (59.4%) underwent surgical resection, 12 (32.4%) received palliative chemotherapy, and the remainder received best supportive care. In the surgical resection group, the median OS was not reached, demonstrating significantly prolonged survival (mean OS, 7.6 years; 5-year OS rate, 51%). In contrast, the median OS was 0.9 years in the palliative chemotherapy group and 0.1 years in the best supportive care group (p = 0.040). Conclusions: Pancreatic ACC showed a broad age distribution, with approximately 20% of patients aged <50 years, and pleomorphic morphological features, including solid, cystic, and mixed patterns. Patients who underwent surgical resection demonstrated favorable long-term survival outcomes compared to historical data for pancreatic ductal adenocarcinoma. Full article

Small intestinal bacterial overgrowth (SIBO) refers to an abnormal increase in the number of bacteria in the small intestine and is observed in various diseases. SIBO can also develop after long-term use of proton pump inhibitors (drug-induced SIBO), bariatric surgery, gastrectomy, and other surgeries (postoperative SIBO). The aim of this narrative review is to summarize all of the published information on the treatment of SIBO in as much detail as possible and present it separately for each specific disease and intervention associated with SIBO. The most extensively studied drug for the treatment of SIBO is rifaximin. It eliminates SIBO in 63% of cases; however, most studies lack a control group. Small RCTs assessing the effects of this antibiotic on SIBO have reported conflicting results, and a meta-analysis showed no effect. A large RCT is required to verify the results of uncontrolled studies. Neomycin and norfloxacin showed efficacy in the treatment of SIBO in single RCTs, with elimination rates of 20 and 100%, respectively. Ciprofloxacin, rifamycin, metronidazole, and other antibiotics, as well as ursodeoxycholic acid, showed positive effects for the treatment of SIBO, but only in uncontrolled studies or in comparison with rifaximin or other drugs. The reported elimination rates were 54%, 67%, 79%, and 75%, respectively. Eradication therapy for Helicobacter pylori infection eliminated SIBO at a rate of approximately 70%. Probiotics have been tested for treatment of SIBO in various diseases. VSL#3 and Saccharomyces boulardii CNCM I-745 were effective in RCTs, with elimination rates of 58% and 80%, respectively. In conclusion, when selecting SIBO treatment regimens, those that have demonstrated the greatest efficacy for a specific concomitant disease should be preferred, despite the generally low level of evidence supporting these approaches in most cases. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy. The identification and management of precursor lesions, particularly the increasingly common intraductal papillary mucinous neoplasms (IPMNs), pose a significant challenge, creating a profound clinical dilemma between intercepting pancreatic ductal adenocarcinoma and avoiding surgical overtreatment. This literature review aims to synthesize the latest evidence to facilitate a transition from purely morphology-based surveillance toward a biologically informed risk stratification paradigm. This approach could provide a personalized risk-stratification algorithm that optimizes therapeutic management and enables timely intervention for pancreatic cancer. By using PubMed, Embase, Scopus, and Web of Science, we analyzed and summarized key findings from recent literature (2020–2025), including cohort studies, mechanistic analyses, evidence-based guidelines, and systematic reviews on cyst fluid biomarkers (CEA panels, DNA/RNA sequencing), and emerging AI applications. Prospective and multicenter studies consistently report that NOD is independently associated with high-risk stigmata, cyst progression, and malignant transformation. Mechanistic research suggests a bidirectional interplay between the evolving neoplasia and pancreatic endocrine dysfunction. Updated guidelines underscore the need for more precise diagnostic algorithms. Recent work demonstrates that advanced cyst fluid markers—CEA panels, DNA/RNA sequencing, and multi-omic signatures—significantly improve diagnostic accuracy. Furthermore, explainable AI models show encouraging performance in predicting malignancy and assisting patient triage. Risk stratification in PCLs is shifting from morphology-based assessment toward integrated, multimodal approaches combining clinical, endocrine, imaging, molecular, and computational data. Recent evidence positions new-onset diabetes as a clinically accessible and biologically plausible marker of high-risk IPMNs. Similarly, molecular assays and AI-enhanced analytics provide an additional layer of diagnostic precision. The development of personalized risk prediction algorithms could improve early detection of malignancy while reducing unnecessary surgical resections. Full article

In this review, we explore the evolving role of endoscopic ultrasound (EUS) in diagnosing and managing pancretobiliary malignancies. For solid pancreatic lesions, techniques like fine-needle biopsy (FNB), contrast-enhanced EUS (CE-EUS), and macroscopic on-site evaluation (MOSE) improve sample quality and diagnostic accuracy. In cystic pancreatic lesions, fine-needle aspiration (FNA), molecular testing, and confocal laser endomicroscopy (nCLE) aid in distinguishing benign from malignant cysts. For cholangiocarcinoma, EUS guided sampling is more accurate than CT in assessing distal lesions and lymph node metastases, while combining EUS with magnetic resonance cholangiography (MRC) enhances diagnostic sensitivity. In gallbladder cancer, EUS surpasses CT and MRI in detecting lymphadenopathy and staging tumors. EUS-FNB (Fine needle biopsy) improves biopsy accuracy, especially for unresectable cases. These advancements highlight EUS as a critical tool for early cancer detection, staging, and tissue acquisition. Beyond diagnosis, EUS plays a pivotal therapeutic role in managing complications such as malignant biliary obstruction and gastric outlet obstruction, offering minimally invasive alternatives like EUS-guided biliary drainage and gastroenterostomy with high clinical success and improved patient outcomes. Full article

Cystic fibrosis is a multi-organ disease in which pancreatic involvement occurs early and contributes significantly to disease progression. Despite this, most mechanistic and pharmacological studies of CFTR have been conducted in airway epithelia, while pancreatic duct models remain relatively poorly represented. In this study, we establish CAPAN-1 cells as a reproducible in vitro model of pancreatic duct epithelium and assess wild-type CFTR function under basal and inflammatory conditions. Cells were cultured as polarized monolayers and analysed for transepithelial conductance, ion transport, luminal fluid pH regulation, and microviscosity. CFTR activity was stimulated with forskolin and further modulated using the potentiator ivacaftor (VX770) and the correctors tezacaftor (VX661) and elexacaftor (VX445), while specificity was confirmed with the CFTR inhibitor PPQ102. Inflammation was induced by lipopolysaccharide (LPS). CAPAN-1 cells formed a functional epithelium. CFTR activation increased epithelial conductance, promoted apical surface fluid alkalinization, and reduced apical surface fluid microviscosity, while PPQ102 consistently inhibited these effects. CFTR modulators enhanced functional responses in the presence of forskolin, although with moderate magnitude, consistent with wild-type CFTR expression. LPS exposure altered epithelial properties, increasing baseline conductance and impairing pH regulation, and induced secretion of pro-inflammatory cytokines. Notably, inflammatory stimulation did not abolish CFTR modulator responses, although it modified some downstream epithelial outputs. These findings identify CAPAN-1 cells as a physiologically relevant model for investigating CFTR function in the pancreatic duct environment and show that CFTR modulator responses are maintained, although functionally reshaped, under inflammatory conditions. Full article

Background: Currently, increasing attention is being paid to the role of genes other than CFTR and their variants as factors modifying the course of cystic fibrosis (CF). One such gene is SLC26A9, which encodes a protein involved in chloride and bicarbonate transport across the epithelial cell membrane. Variants of SLC26A9, such as c.229G>A (p.Gly77Ser) and c.1885C>T (p.Pro629Ser), have been described in patients with severe and rapidly progressive CF. The aim of this study was to identify SLC26A9 variants in a group of 20 patients with CF. Methods: DNA was isolated from blood samples and collected from all patients. Fragments of exons 3 and 17 of the SLC26A9 gene were amplified by PCR and sequenced using the Sanger method. Results: An SLC26A9 variant was identified in two siblings. These patients were diagnosed with CF in adulthood and presented with moderate pulmonary symptoms without exocrine pancreatic insufficiency. In both siblings carrying the CFTR variants p.Phe508del and c.3140-26A>G, the SLC26A9 variant c.1847C>T (p.Pro616Leu) was detected. This variant has not been widely described in the literature and has not previously been associated with CF. Conclusions: The c.1847C>T (p.Pro616Leu) variant is located near a domain that may affect the transport function of the SLC26A9 protein. However, patients in whom the variant was identified did not present a severe disease phenotype. Further studies on larger patient cohorts are required, and at present this variant should be considered of uncertain significance in CF. Full article

Magnetic resonance imaging (MRI) plays an essential role in cancer detection and surveillance, yet complete MRI (C-MRI) protocols are lengthy, resource-intensive, and may limit access within population-level cancer care pathways. Abbreviated MRI (A-MRI) protocols have emerged as a streamlined alternative that may preserve diagnostic performance while reducing examination time, cost, and IV contrast exposure. We conducted a narrative review of studies published between 2015 and 2025 evaluating A-MRI in prostate cancer detection and surveillance, pancreatic cystic lesion surveillance, and hepatocellular carcinoma (HCC) surveillance. Evidence was synthesized qualitatively with emphasis on potential advantages, limitations, guideline positions, and evidence gaps. Across the organ systems assessed, A-MRI may demonstrate diagnostic performance comparable to C-MRI in selected clinical contexts. Biparametric MRI has demonstrated noninferior detection of clinically significant prostate cancer; non-contrast A-MRI may be considered for the surveillance of selected low-risk pancreatic cystic lesions, and A-MRI may offer higher sensitivity than ultrasound for HCC surveillance in patients with suboptimal ultrasound visualization. Heterogeneity in the available literature and limited prospective outcome data remain important limitations. Overall, A-MRI represents a complementary, risk-adapted strategy rather than a universal replacement for C-MRI, and further prospective studies are needed to define optimal patient selection and long-term oncologic benefit. Full article

Background/Objectives: Pancreatic cancer (PC) should be diagnosed in its early stages. Therefore, it is necessary to identify high-risk individuals of PC. Methods: Between 2001 and 2017, 1542 PC cases were diagnosed at two tertial care institutions. Of these, 117 cases had undergone abdominal contrast-enhanced computed tomography (CE-CT) 1–10 years before PC diagnosis and were classified as the PC group. Meanwhile, 43,102 cases underwent abdominal CE-CT for close examination of non-pancreatic diseases in the same period, of which 1170 were randomly selected. Of these, 117 cases were matched to the PC group with the propensity score and designated the non-PC group. Pancreatic volumetry was performed using the 3D image analysis system for abdominal CE-CT in both groups and various measurements were compared. In PC group, CE-CT taken 1–10 years before the onset of PC was analyzed. Results: After propensity score matching, baseline characteristics did not significantly differ between the two groups. The whole pancreatic volume/body surface area (BSA) (p = 0.014), volume of main pancreatic duct (MPD) plus cystic lesion/BSA (p < 0.001), volume of pancreatic parenchyma/BSA (p = 0.002), ratio of cross-sectional areas (p = 0.033), and MPD diameter/BSA (p < 0.001) significantly differed between the two groups. In subgroup analysis of patients without cystic lesions, the whole pancreatic volume/BSA, volume of MPD/BSA, volume of pancreatic parenchyma/BSA, ratio of cross-sectional areas, and MPD diameter/BSA significantly differed between the two groups. Conclusions: Pancreatic volumetry could identify patients at high risk of PC. Full article

Pancreatic cystic lesions (PCLs) represent a growing clinical challenge due to their diverse biological behaviors and the substantial overlap in imaging features between benign, premalignant, and malignant entities. Traditional diagnostic approaches relying on cross-sectional imaging or isolated morphologic criteria frequently fail to achieve adequate risk discrimination. Advances in endoscopic ultrasound (EUS) now permit detailed morphologic assessment complemented by cyst-fluid biochemical markers, proteomic signatures, and comprehensive genomic profiling using next-generation sequencing. Parallel progress in artificial intelligence (AI) further strengthens diagnostic precision by integrating EUS features with multimodal biomarker data to reduce subjectivity and support individualized clinical decision-making. This review introduces an EUS-based multimodal diagnostic framework of PCLs that integrates morphological evaluation, cyst-fluid biochemical testing, molecular profiling, and AI-assisted analysis. By synthesizing current evidence, we outline how the integrative approach enhances diagnostic accuracy, biological interpretability, and individualized risk stratification for PCLs. Full article