Search Results (118)

Background: A dilated main pancreatic duct (MPD) ≥ 5 mm can be observed in main-duct IPMNs (MD-IPMN) and chronic pancreatitis (CP); however, distinguishing between the two differently treated diseases can be difficult. Cell-free (cf) DNA in MPD fluid obtained by EUS-guided FNA might help to distinguish MD-IPMN from CP. Methods: All patients with a dilated MPD ≥ 5 mm on EUS during the period of 1 June 2017 to 30 April 2024 were prospectively analysed in this single-centre study, with EUS-guided MPD fluid aspiration performed for suspected MD-IPMN or CP in patients who were suitable for surgery. Twenty-two known gastrointestinal cancer genes, including GNAS and KRAS, were analysed by deep targeted (dt) NGS. The results were correlated with resected tissue, biopsy, and long-term follow-up. Results: A total of 164 patients with a dilated MPD were identified, of which 30 (18.3%) underwent EUS-guided FNA, with 1 patient having a minor complication (3.3%). Twenty-two patients (mean MPD diameter of 12.4 (7–31) mm) with a definitive, mostly surgically confirmed diagnosis were included in the analysis. Only a fish-mouth papilla, which was present in 3 of 12 (25%) MD-IPMNs, could reliably differentiate between the two diseases, with history, symptoms, diffuse or segmental MPD dilation, presence of calcifications on imaging, cytology, and CEA in the ductal fluid failing to achieve differentiation. However, GNAS mutations were found exclusively in 11 of the 12 (91.6%) patients with MD-IPMN (p < 0.01), whereas KRAS mutations were identified in both diseases. Conclusions: GNAS testing by dtNGS in aspirated fluid from dilated MPD obtained by EUS-guided FNA may help differentiate MD-IPMN from CP for surgical resection. 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: Early detection of pancreatic cancer using existing tumor markers is challenging, and novel biomarkers are needed. Apolipoprotein A2 (APOA2), which is not directly produced by tumors, may help detect pancreatic cancer through mechanisms distinct from carbohydrate antigen 19-9 (CA 19-9). This study aimed to evaluate the diagnostic performance of the APOA2-isoform (APOA2-i) Index in patients with pancreatic cancer. Methods: Serum levels of the APOA2-i Index and CA 19-9 were measured in 76 patients with pancreatic cancer (Stage 0, n = 5; I, n = 4; II, n = 15; III, n = 19; and IV, n = 33) and 98 patients with non-pancreatic cancer (intraductal papillary mucinous neoplasm, n = 36; chronic pancreatitis, n = 33; pancreatic neuroendocrine neoplasm, n = 8; autoimmune pancreatitis, n = 9; and others, n = 12) to evaluate diagnostic performance. Results: APOA2 showed lower accuracy for advanced (stages II–IV) pancreatic cancer compared to CA 19-9 (sensitivity, 50.7% vs. 83.6%; sensitivity, 77.6% vs. 87.9%), but it provided superior accuracy for early-stage (stages 0 and I) detection (sensitivity, 33.3% vs. 22.2%; specificity, 66.7% vs. 59.4%). Three early-stage pancreatic cancer cases negative for CA 19-9 were detected with the APOA2-i Index, demonstrating high diagnostic accuracy for early-stage pancreatic cancer when both biomarkers are combined (sensitivity, 44.4%; specificity, 46.7%). The multivariate analysis revealed pancreatic cancer to be an independent risk factor for APOA2-i Index positivity (odds ratio [OR]: 3.48, p < 0.001), CA 19-9 positivity (OR: 25.5, p < 0.001), and positivity for either marker (OR: 13.3, p < 0.001). Conclusions: The APOA2-i Index, combined with CA 19-9, may improve early-stage pancreatic cancer detection, especially in challenging cases and for high-risk patient surveillance. 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

Background: The effect of differing post-contrast phases on CT body composition measurements is not yet known. Methods: A fully automated AI-based body composition analysis using DAFS was performed on a retrospective cohort of 278 subjects undergoing pre-treatment triple-phase CT for pancreatic intraductal papillary mucinous neoplasm. The CT contrast phases included noncontrast (NON), arterial (ART), and venous (VEN) phases. The software selected a single axial CT image at mid-L3 on each phase for body compartment segmentation. The areas (cm²) were calculated for skeletal muscle (SM), intermuscular adipose tissue (IMAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). The mean Hounsfield units of skeletal muscle (SMHU) within the segmented regions were calculated. Bland–Altman and Chi Square analyses were performed. Results: SM-NON had a lower percentage of bias [LOA] than SM-ART, −0.7 [−7.6, 6.2], and SM-VEN, −0.3 [−7.6, 7.0]; VAT-NON had a higher percentage of bias than ART, 3.4 [−18.2, 25.0], and VEN, 5.8 [−15.0, 26.6]; and this value was lower for SAT-NON than ART, −0.4 [−14.9, 14.2], and VEN, −0.5 [−14.3, 13.4]; and higher for IMAT-NON than ART, 5.9 [−17.9, 29.7], and VEN, 9.5 [−17.0, 36.1]. The bias in SMHU NON [LOA] was lower than that in ART, −3.8 HU [−9.8, 2.1], and VEN, −7.8 HU [−14.8, −0.8]. Conclusions: IV contrast affects the voxel HU of fat and muscle, impacting CT analysis of body composition. We noted a relatively smaller bias in the SM, VAT, and SAT areas across the contrast phases. However, SMHU and IMAT experienced larger bias. During threshold risk stratification for CT-based measurements of SMHU and IMAT, the IV contrast phase should be taken into consideration. Full article

Objectives: The present study aimed to validate the new international guidelines for IPMN and determine the surgical criteria for patients with IPMN exhibiting high-risk stigmata (HRS). Methods: We enrolled 115 IPMN patients exhibiting HRS who were diagnosed between 2004 and 2021. Of the 115 patients, 79 underwent surgery (surgical group) and 36 did not undergo surgery (non-surgical group). The overall survival (OS) of each group was compared, and multivariate analysis was performed to identify factors associated with OS. Results: There was no significant difference in the estimated 5-year OS in the surgical and non-surgical groups (67% vs. 74%; p = 0.75). The presence of a solid component (SC) (hazard ratio [HR], 6.92; 95% confidence interval [CI], 3.30–14.5) and a high score of age-adjusted Charlson comorbidity index (ACCI) (≥5) (HR, 2.27; 95% CI, 1.11–4.64) were independent predictors of poor OS. In the presence of an SC, the surgical group had a significantly better OS than the non-surgical group (estimated 5-year OS, 38% vs. 18%; p = 0.031). In the absence of an SC, the prognosis of patients with a high ACCI was significantly poorer than those with a low ACCI in the surgical group (estimated 5-year OS, 59% vs. 93%; p = 0.005). Conclusions: An SC and a high ACCI are important prognostic factors in IPMN patients exhibiting HRS. Thus, patients with an SC should undergo surgical resection. However, conservative management may be the optimal treatment in patients without an SC and with a high ACCI. Full article