Search Results (90)

Early diagnosis of pancreatic cancer, particularly in intraductal papillary mucinous neoplasm (IPMN), remains challenging despite advances in imaging and biomarkers. Pancreatic adenocarcinoma (PDAC) has a high mortality rate; therefore, its early detection and adequate interventions are necessary to improve the disease outcome. Most IPMNs are asymptomatic and discovered incidentally. Magnetic resonance imaging (MRI) is a preferred tool for diagnosing malignant IPMNs, with a sensitivity of 90.7–94.1% and a specificity of 84.7–87.2% in detecting mural nodules > 5 mm, a strong predictor of high-risk lesions. Radiomics further enhances diagnostic accuracy (sensitivity 91–96%, specificity 78–81%), especially when combined with CA 19-9, which has lower sensitivity (73–90%) but higher specificity (79–95%). Computed tomography (CT), though less effective for small mural nodules, remains widely used; its accuracy improves with radiomics and clinical variables (sensitivity 90.4%, specificity 74%). Conventional endoscopic ultrasonography (EUS) shows lower performance (sensitivity 60%, specificity 80%), but its advanced variations have improved outcomes. Contrast-enhanced EUS (CE-EUS) visualizes mural nodules with more than 90% sensitivity and involvement of the main pancreatic duct, with a sensitivity of 83.5% and a specificity of 87%. EUS–fine-needle aspiration (EUS-FNA) allows cyst fluid analysis; however, CEA, glucose, and KRAS/GNAS mutations show poor value for malignancy risk. Cytology has low sensitivity (28.7–64.8%) but high specificity (84–94%) in diagnostic malignant changes and strongly affects further management. EUS–through-the-needle biopsy (EUS-TTNB) yields high diagnostic accuracy (sensitivity 90%, specificity 95%) but carries a range of 2–23% adverse events, which limits its wide use. EUS–confocal laser endomicroscopy (EUS-nCLE) provides real-time microscopic evaluation, detecting malignant IPMN with a sensitivity of 90% and a specificity of 73%, though its availability is limited. New emerging biomarkers available in cyst fluid or blood include mucins, miRNA panels (sensitivity 66.7–89%, specificity 89.7–100%), lipidomics, and cancer metabolite profiling, with diagnostic accuracy approaching 89–91%. Pancreatoscopy (POP) enables direct main pancreatic duct (MPD) visualization and biopsy with a sensitivity of 64–100% and a specificity of 75–100%, though adverse events occur in around 12% cases. Combining advanced imaging, EUS-based tissue acquisition, and novel biomarkers holds promise for earlier and more accurate detection of malignant IPMN, potentially improving PDAC outcomes. Full article

The management of type 2 diabetes in patients with intraductal papillary mucinous neoplasms (IPMNs) presents a growing clinical dilemma. As glucagon-like peptide-1 receptor agonists (GLP-1RAs) become first-line therapies for diabetes and obesity, their safety in patients with premalignant pancreatic lesions remains uncertain. This viewpoint examines current evidence through three critical lenses: molecular mechanisms linking incretin signaling to IPMN progression, clinical outcomes from large-scale pharmacovigilance studies, and practical management considerations. We propose a risk-stratified approach that balances the proven metabolic benefits of GLP-1RAs against theoretical oncogenic risks, emphasizing the need for shared decision-making and enhanced surveillance protocols. Full article

Background: Pancreatic cystic lesions (PCLs), including intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), pose a diagnostic challenge due to their variable malignant potential. Current guidelines, such as Fukuoka and American Gastroenterological Association (AGA), have moderate predictive accuracy and may lead to overtreatment or missed malignancies. Artificial intelligence (AI), incorporating machine learning (ML) and deep learning (DL), offers the potential to improve risk stratification, diagnosis, and management of PCLs by integrating clinical, radiological, and molecular data. This is the first systematic review to evaluate the application, performance, and clinical utility of AI models in the diagnosis, classification, prognosis, and management of pancreatic cysts. Methods: A systematic review was conducted in accordance with PRISMA guidelines and registered on PROSPERO (CRD420251008593). Databases searched included PubMed, EMBASE, Scopus, and Cochrane Library up to March 2025. The inclusion criteria encompassed original studies employing AI, ML, or DL in human subjects with pancreatic cysts, evaluating diagnostic, classification, or prognostic outcomes. Data were extracted on the study design, imaging modality, model type, sample size, performance metrics (accuracy, sensitivity, specificity, and area under the curve (AUC)), and validation methods. Study quality and bias were assessed using the PROBAST and adherence to TRIPOD reporting guidelines. Results: From 847 records, 31 studies met the inclusion criteria. Most were retrospective observational (n = 27, 87%) and focused on preoperative diagnostic applications (n = 30, 97%), with only one addressing prognosis. Imaging modalities included Computed Tomography (CT) (48%), endoscopic ultrasound (EUS) (26%), and Magnetic Resonance Imaging (MRI) (9.7%). Neural networks, particularly convolutional neural networks (CNNs), were the most common AI models (n = 16), followed by logistic regression (n = 4) and support vector machines (n = 3). The median reported AUC across studies was 0.912, with 55% of models achieving AUC ≥ 0.80. The models outperformed clinicians or existing guidelines in 11 studies. IPMN stratification and subtype classification were common focuses, with CNN-based EUS models achieving accuracies of up to 99.6%. Only 10 studies (32%) performed external validation. The risk of bias was high in 93.5% of studies, and TRIPOD adherence averaged 48%. Conclusions: AI demonstrates strong potential in improving the diagnosis and risk stratification of pancreatic cysts, with several models outperforming current clinical guidelines and human readers. However, widespread clinical adoption is hindered by high risk of bias, lack of external validation, and limited interpretability of complex models. Future work should prioritise multicentre prospective studies, standardised model reporting, and development of interpretable, externally validated tools to support clinical integration. Full article

Endoscopic ultrasonography represents a crucial aspect of the diagnosis of pancreatic lesions. The echo-endoscopic features of pancreatic lesions, particularly their contrast behavior with the advent of Contrast-Enhanced EUS (CE-EUS) and Contrast Enhanced Harmonic-EUS (CH-EUS), can predict a lesion’s aggressiveness, depending on its nature. According to this, CH-EUS could be applied to structure an even more dedicated approach to patient care, for example, to ascertain eligibility for surgical intervention of a pancreatic ductal adenocarcinoma (PDAC) or the response to neoadjuvant chemotherapy in cases deemed borderline resectable. In addition to PDAC, other significant issues pertain to the management of small neuroendocrine tumors (NETs) and intraductal papillary mucinous neoplasms (IPMNs). In this context, CH-EUS can be crucial. The aim of this review is to underline the most recent evidence for EUS and CH-EUS applications in pancreatic lesion aggressiveness assessment and to focus on possible future research directions to further extend the application of CH-EUS in this field. Full article

Background and Aims: An appropriate surveillance system must be established to efficiently identify cases of intraductal papillary mucinous neoplasm (IPMN)-related malignant transformation. We analyzed the initial clinical background that affects long-term prognosis and narrowed the population for whom continued evaluation is inevitable. Methods: We included 1645 patients with IPMN treated at our hospital since 2010. We examined the types and timing of malignant transformation in terms of the worrisome features (WFs). The chi-squared test, log-rank test, and Cox proportional hazards model were used for the analysis (statistical significance at α = 0.05). Results: In total, 123 (7.5%) and 41 patients (2.5%) had IPMN-derived carcinoma (IPMN-DC) and concomitant pancreatic ductal adenocarcinoma (c-PDAC), respectively. Compared with IPMN-DC, a significantly higher proportion of c-PDAC patients were diagnosed with an advanced disease stage that developed earlier. The factors with significantly shorter time for IPMN-DC development were maximum cyst diameter (MCD) ≥ 30 mm, nonbranched type, main pancreatic duct (MPD) diameter ≥ 5 mm, and septal nodal structure (SNS) for IPMN-DC, and MCD ≥ 30 mm, main duct type, MPD ≥ 5 mm, SNS, cyst enlargement (≥2.5 mm/year), and abnormal CA19-9 levels for c-PDAC. Both groups could be significantly stratified by the number of WFs. A relative risk analysis revealed that SNS, MCD ≥ 30 mm, and MPD ≥ 5 mm were significant factors for IPMN-DC, whereas abnormal CA19-9 and SNS were significant for c-PDAC. Conversely, significantly more patients exhibiting these factors initially later developed IPMN-DC or c-PDAC. Conclusions: Ten percent of IPMN cases will develop IPMN-DC or c-PDAC, thereby requiring careful follow-up, especially in cases with SNS, abnormal CA19-9, and MCD ≥ 30 mm. Full article

Background/Objectives: Pancreatic neoplasms, including adenocarcinoma, pancreatic neuroendocrine tumors (pNETs), intraductal papillary mucinous neoplasms (IPMNs), and high-grade cystic lesions, often require surgical resection as a form of curative treatment. However, comorbidities and high-risk features may preclude surgery. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as a minimally invasive alternative with proven cytoreductive efficacy in solid tumors. This case series evaluates the safety and efficacy of EUS-RFA in patients with various unresectable, non-metastatic pancreatic neoplasms. Methods: A retrospective review was conducted on eight patients who underwent EUS-RFA at our institutions between July 2021 and February 2025. All patients were deemed unsuitable surgical candidates due to comorbidities such as advanced age, cardiovascular disease, renal insufficiency, and COPD or due to patient resistance to surgical intervention. EUS-RFA was performed using a 19-gauge RFA needle (Taewoong Corporation). Follow-up imaging was conducted 3 to 6 months after the completion of RFA treatment. Results: All eight patients demonstrated a good to excellent response in terms of tumor size reduction. The most notable response was observed in a patient with pNET, resulting in complete resolution from 15.6 × 12.0 mm to 0.0 × 0.0 mm after two RFA treatments. Other neoplasms, including pancreatic adenocarcinoma and intraductal papillary mucinous neoplasms (IPMNs), also demonstrated significant reductions. Mild post-procedure complications, including pancreatitis and abdominal pain, were noted in three cases. Conclusions: EUS-RFA is a promising alternative for managing unresectable pancreatic neoplasms in high-risk patients. Our findings support its use across various tumor types with favorable outcomes and minimal complications, reinforcing its role in expanding therapeutic options beyond surgery. Full article

Pancreatic cystic lesions (PCLs) are increasingly identified via computerized tomography (CT) and magnetic resonance (MR), with a prevalence of 2–45%. Distinguishing mucinous PCLs (M-PCLs), which include intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) that can progress to pancreatic ductal adenocarcinoma, from non-mucinous PCLs (NM-PCLs) is essential. Carcinoembryonic antigen (CEA) remains widely used but often demonstrates limited sensitivity and specificity. In contrast, endoscopic ultrasound-guided measurement of intracystic glucose more accurately differentiates PCL subtypes, as tumor-related metabolic changes lower cyst fluid glucose in mucinous lesions. Numerous prospective and retrospective studies suggest a glucose cut-off between 30 and 50 mg/dL, yielding a sensitivity of 88–95% and specificity of 76–91%, frequently outperforming CEA. Additional benefits include immediate point-of-care assessment via standard glucometers and minimal interference from blood contamination. DNA-based biomarkers, including KRAS and GNAS mutations, enhance specificity (up to 99%) but exhibit moderate sensitivity (61–71%) and necessitate specialized, expensive platforms. Molecular analyses can be crucial in high-risk lesions, yet their uptake is constrained by technical challenges. In practice, combining glucose assessment with targeted molecular assays refines risk stratification and informs the choice between surgical resection or active surveillance. Future investigations should establish standardized glucose thresholds, improve the cost-effectiveness of genetic testing, and integrate advanced biomarkers into routine protocols. Ultimately, these strategies aim to optimize patient management, limit unnecessary interventions for benign lesions, and ensure timely therapy for lesions at risk of malignant transformation. Full article

Background: Intraductal papillary mucinous neoplasms (IPMNs) are pre-malignant pancreatic lesions that may progress to invasive pancreatic ductal adenocarcinoma (PDAC). IPMN-associated invasive carcinoma (iIPMN) has been associated with more favorable survival outcomes compared to non-iIPMN-derived PDAC. Here, we aim to investigate the genetic landscape of IPMNs to assess their relevance to oncologic outcomes. Methods: This retrospective study used a large single-institution prospectively maintained database. Patients who underwent curative-intent pancreatic resection between 2016 and 2022 with histologically confirmed diagnosis of IPMN were included. Demographic, pathologic, molecular, and oncologic outcome data were recorded. Kaplan–Meier survival analyses were performed. PDAC data from public genetic databases were used for mutational correlation analysis. p-value ≤ 0.05 was considered as significant. Results: A total of thirty-nine patients with resected IPMN with complete clinical and sequencing data were identified and included in the final cohort. The male-to-female distribution was 21:18, and the mean age was 70.1 ± 9.1 years. GNAS mutations occurred in 23.1% of patients, and 89.7% of patients had iIPMN. In iIPMN patients, GNAS mutation was strongly associated with improved disease-free survival: all GNAS-mutant patients survived to follow-up with significantly fewer recurrences than in GNAS wild-type (WT) patients (p = 0.013). Mutated GNAS closely co-occurred with wild-type KRAS (p < 0.001), and further analysis of large genomic PDAC datasets validated this finding (OR 3.47, p < 0.0001). Conclusions: Our study suggests prognostic value of mutational status in malignant resected IPMNs. WT GNAS, mutant P53, and mutant KRAS each correlate with recurrence and decreased survival. Further studies are required to validate these preliminary observations. Full article

Objectives: Pancreatic cystic neoplasms (PCNs), particularly intraductal papillary mucinous neoplasms (IPMNs), present a challenge for their potential malignancy. Despite promising biomarkers like CEA, amylase, and glucose, our study investigates whether metabolic indices in blood and cystic fluids (CFs), in addition to lymphocyte subsets and hematopoietic stem/progenitor cells (HSPCs), can effectively differentiate between high- and low-risk PCNs. Materials and Methods: A total of 26 patients (11 males, mean age 69.5 ± 9 years) undergoing Endoscopic Ultrasound-guided Fine Needle Aspiration were consecutively enrolled. Analyses included blood, serum, and CF, assessing glucose, CEA, cholesterol (total, HDL, and LDL), and total proteins. Flow cytometry examined immunophenotyping in peripheral blood and cystic fluids. Mass spectrometry was used for the metabolomic analysis of CF. Sensitivity, specificity, and ROC analyses evaluated discriminatory power. Results: A total of 25 out of 26 patients had IPMN. Patients were categorized as low or high risk based on multidisciplinary evaluation of clinical, radiological, and endoscopic data. High-risk patients showed lower CF total proteins and LDL cholesterol (p = 0.005 and p = 0.031), with a marked reduction in CF lymphocytes (p = 0.005). HSCPs were absent in CF. In blood, high-risk patients showed increased non-MHC-restricted cytotoxic T cells (p = 0.019). The metabolomic analysis revealed significantly reduced middle and long-chain acyl carnitines (AcCa) and tryptophan metabolites in high-risk patients. ROC curves indicated comparable discriminant abilities for CF lymphocytes (AUC 0.868), CF total proteins (AUC 0.859), and CF LDL cholesterol (AUC 0.795). The highest performance was achieved by the AcCa 14:2 and 16:0 (AUC: 0.9221 and 0.8857, respectively). Conclusions: CF levels of glucose, CEA, LDL cholesterol, and total proteins together with lymphocyte counts are easy translational biomarkers that may support risk stratification of PCNs in IPMN patients and might be endorsed by metabolomic analysis. Further studies are required for potential clinical integration. Full article

Background/Objectives: Detective flow imaging (DFI) endoscopic ultrasonography (EUS) can identify the microvascular flow imaging of a mural nodule (MN) in an intraductal papillary mucinous neoplasm (IPMN) without the use of contrast agents. This retrospective study evaluated the diagnostic accuracy of DFI-EUS and its ability to evaluate the blood flow of MNs in IPMNs. Methods: Between April 2021 and September 2023, 68 patients with MNs in IPMNs observed on EUS images were retrospectively analyzed. Both DFI-EUS and contrast-enhanced EUS (CE-EUS) were performed during the same session. Three expert endosonographers blinded to the patients’ clinical data assessed the MN images obtained with CE-EUS and DFI-EUS. First, DFI-EUS images were evaluated using a predefined scoring system; thereafter, CE-EUS images were evaluated. The diagnostic capability of DFI-EUS to detect MN blood flow was assessed with CE-EUS as the gold standard. Secondary outcomes included inter-reader agreement, the correlation between MN size and detection rates, and the association between DFI blood flow signal patterns and malignancy of MNs in surgically resected cases. Results: CE-EUS showed a contrast effect in the MN in 24 cases. Among these, DFI-EUS detected blood flow signals in 20 cases; false-positive results were not observed. DFI-EUS demonstrated a sensitivity of 83%, specificity of 100%, and accuracy of 93% for detecting MN blood flow. Inter-reader agreement was substantial (kappa values, 0.6–0.8). The subgroup analysis revealed that all MNs ≥ 10 mm had detectable blood flow on DFI-EUS, whereas MNs < 10 mm had reduced detection rates (75%; 12/16 cases). No significant correlation between the DFI blood flow signal patterns and MN malignancy of resected cases was observed. Conclusions: DFI-EUS demonstrated high diagnostic accuracy for detecting MN blood flow. Because of its simplicity and cost-effectiveness, DFI-EUS could be an alternative to CE-EUS for patients with MNs inside IPMNs. Full article

Endoscopic ultrasound (EUS) effectively diagnoses malignant and pre-malignant gastrointestinal lesions. In the past few years, artificial intelligence (AI) has shown promising results in enhancing EUS sensitivity and accuracy, particularly for subepithelial lesions (SELs) like gastrointestinal stromal tumors (GISTs). Furthermore, AI models have shown high accuracy in predicting malignancy in gastric GISTs and distinguishing between benign and malignant intraductal papillary mucinous neoplasms (IPMNs). The utility of AI has also been applied to existing and emerging technologies involved in the performance and evaluation of EUS-guided biopsies. These advancements may improve training in EUS, allowing trainees to focus on technical skills and image interpretation. This review evaluates the current state of AI in EUS, covering imaging diagnosis, EUS-guided biopsies, and training advancements. It discusses early feasibility studies and recent developments, while also addressing the limitations and challenges. This article aims to review AI applications to EUS and its applications in clinical practice while addressing pitfalls and challenges. Full article

Background and Aims: A higher incidence of extra-pancreatic malignancies (EPMs) in patients with pancreatic intraductal papillary mucinous neoplasm (IPMN) than in the general population has been shown in several studies. We suppose that EPMs also occur after IPMN has been diagnosed, but few reports have discussed the risk factors that have been identified, except for old age, which was only noted in one study. Our study aims to recognize the distribution of EPMs in Taiwanese patients with a longer duration of follow-up and investigate the risk factors to predict EPMs in IPMN patients. Methods: We retrospectively analyzed 114 patients with pancreatic IPMN from 1 January 2010 to 31 December 2014 in Chang Gung Memorial Hospital. The characteristics of the patients were all recorded. Different EPMs are demonstrated as occurring before, concurrently with, or after IPMN diagnosis. The risk factors were compared between patients with or without an EPM. Results: After an average follow-up duration of 10.45 years, 47 EPMs occurred in 42 patients (36.8%), and over half were found after IPMN was diagnosed (55.3%). The most common EPMs were colon cancer and lung cancer (21.3%). Moreover, cyst size progression was highly associated with EPM occurrence (p = 0.004) and predictive of EPM occurrence after IPMN (p = 0.002), with a cut-off value of 1 cm (accuracy: 79%; sensitivity: 88%; specificity: 58%). Conclusions: Colon cancer and lung cancer account for the majority EPMs in Taiwan. EPMs were also frequently found after IPMN diagnosis when the follow-up duration was prolonged up to 10.45 years. Cyst size progression is a risk factor of EPM after IPMN diagnosis and we suggest a cut-off value of 1 cm for clinical utility. Full article

Intraductal papillary mucinous neoplasms (IPMN) are commonly detected pancreatic cysts that may transform into pancreatic ductal adenocarcinoma (PDAC). Predicting which IPMNs will progress to PDAC remains a clinical challenge. Moreover, identifying those clinically evident IPMNs for which a surveillance approach is best is a dire clinical need. Therefore, we aimed to identify molecular signatures that distinguished between PDAC with and without clinical evidence of an IPMN to identify novel molecular pathways related to IPMN-derived PDAC that could help guide biomarker development. Data from the Oncology Research Information Exchange Network (ORIEN) multi-institute sequencing project were utilized to analyze 66 PDAC cases from Moffitt Cancer Center and The Ohio State University Wexner Medical Center, for which tumor whole transcriptome sequencing datasets were generated. Cases were classified based on whether a tumor had originated from an IPMN (n = 16) or presumably through the pancreatic intraepithelial neoplasia (PanIN) pathway (n = 50). We then performed differential expression and pathway analysis using Gene-Set Enrichment Analysis (GSEA) and Pathway Analysis with Down-weighted Genes (PADOG) algorithms. We also analyzed immune profiles using the Tumor-Immune Microenvironment Deconvolution web portal for Bulk Transcriptomics (TIMEx). Both GSEA and TIMEx indicate that PanIN-derived PDAC tumors enrich inflammatory pathways (complement, hedgehog signaling, coagulation, inflammatory response, apical surface, IL-2/STAT5, IL-6/STAT3, EMT, KRAS signaling, apical junction, IFN-gamma, allograft rejection) and are comparatively richer in almost all immune cell types than those from IPMN-derived PDAC. IPMN-derived tumors were enriched for metabolic and energy-generating pathways (oxidative phosphorylation, unfolded protein response, pancreas beta cells, adipogenesis, fatty acid metabolism, protein secretion), and the most significantly upregulated genes (padj < 0.001) included mucin 2 (MUC2) and gastrokine-2 (GKN2). Further, the metabolic-linked gene signature enriched in the IPMN-derived samples is associated with a cluster of early-stage and long-survival (top 4th quartile) PDAC cases from The Cancer Genome Atlas (TCGA) expression database. Our data suggest that IPMN-derived and PanIN-derived PDACs differ in the expression of immune profiles and metabolic pathways. These initial findings warrant validation and follow-up to develop biomarker-based strategies for early PDAC detection and treatment. Full article

Currently, there is no reliable method of discerning between low-risk and high-risk intraductal papillary mucinous neoplasms (IPMNs). Operative resection is utilized in an effort to resect those lesions with high-grade dysplasia (HGD) prior to the development of invasive disease. The current guidelines recommend resection for IPMN that involve the main pancreatic duct. Resecting lesions with HGD before their progression to invasive disease and the avoidance of resection in those patients with low-grade dysplasia is the optimal clinical scenario. Therefore, the importance of developing preoperative models able to discern HGD in IPMN patients cannot be overstated. Low-risk patients should be managed with nonsurgical treatment options (typically MRI surveillance), while high-risk patients would undergo resection, hopefully prior to the formation of invasive disease. Current research is evolving in multiple directions. First, there is an ongoing effort to identify reliable markers for predicting malignant transformation of IPMN, mainly focusing on genomic and transcriptomic data from blood, tissue, and cystic fluid. Also, multimodal models of combining biomarkers with clinical and radiographic data seem promising for providing robust and accurate answers of risk levels for IPMN patients. Full article

Background: Intraductal papillary mucinous neoplasms (IPMNs) display four histological subtypes: gastric foveolar, pancreaticobiliary, intestinal, and oncocytic. All of these subtypes harbor a different risk of cancer development. The clinical impact of these subtypes concerning the occurrence of high-grade dysplasia (HGD)/cancer (C) in specific morphological types, such as branch-duct (BD), main-duct (MD), and mixed-type (MT) IPMNs, has been less investigated. Hence, our aim was to investigate the prevalence of histological subtypes and their possible association with HGD/C concerning morphologically different IPMNs. Methods: This was a retrospective review of demographics, risk factors, and histological features in a surgical cohort of patients having undergone resection for suspect malignant IPMNs at a high-volume tertiary center from 2007 to 2017. Results: A total of 273 patients were resected for IPMNs from during the study period, of which 188 were included in the final analysis. With sex- and age-adjusted multivariable logistic regression analysis across the entire cohort, gastric foveolar subtypes were associated with a reduced prevalence of HGD/C (OR = 0.30; 0.11–0.81, 95% CI, 95%CI; p = 0.01). With univariable logistic regression analysis, in the BD-IPMN subgroup, the pancreaticobiliary subtype was associated with an increased prevalence of HGD/C (OR = 18.50, 1.03–329.65, 95% CI; p = 0.04). In MD- and MT-IPMNs, the gastric foveolar subtype was associated with a decreased prevalence of HGD/cancer (OR = 0.30, 0.13–0.69, 95% CI; p = 0.004). Conclusions: In MD and MT-IPMNs, the gastric-foveolar subtype is associated with a lower prevalence of HGD/C, possibly identifying in such a high-risk group, a subgroup with more indolent behavior. In BD-IPMNs, the pancreaticobiliary subtype is associated with a higher prevalence of HGD/C, conversely identifying among those patients, a subgroup deserving special attention. Full article