Search Results (87)

Pancreatic cystic lesions (PCLs) are increasingly detected due to widespread use of cross-sectional imaging. They encompass a heterogeneous group of lesions, ranging from benign pseudocysts and serous cystic neoplasms (SCNs) to premalignant mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs), as well as rare malignant entities such as solid pseudopapillary epithelial neoplasm (SPENs) and cystic pancreatic neuroendocrine tumors (cystic PanNETs). Management of PCLs depends on their malignant potential; therefore, an accurate classification is essential for optimizing treatment. This narrative review summarizes current knowledge on the epidemiology, imaging characteristics, diagnosis, and management of PCLs, highlighting the role of CT, MRI, MRCP, and endoscopic ultrasound. Recent advances in radiomics for lesion characterization and risk stratification, particularly in IPMNs, are discussed. Full article

Objectives: Pancreatic cystic lesions (PCLs) are increasingly detected due to the widespread use of imaging techniques. The identification of pancreatic mucinous cysts is especially important since these carry a risk of malignant transformation and require follow-up or surgical resection. The aim of this study was to determine the diagnostic yield of the molecular analysis of K-RAS (Kirsten RAt Sarcoma virus) and GNAS (Guanine Nucleotide-binding protein, Alpha Stimulating protein activity) gene mutations in pancreatic cyst fluid (PCF) obtained by endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA). Methods: In this prospective trial, we assessed the sensitivity, specificity, and positive and negative predictive values of K-RAS and GNAS mutation analysis in differentiating mucinous versus non-mucinous cysts and the subsequent impact on decision-making in daily clinical practice. The reference standard used comprised the combination of morphology on cross-sectional imaging and EUS, string sign, cyst fluid cytology, intracystic carcinoembryonic antigen (CEA), and glucose levels, with subsequent correlation of surgical pathology in resected cases. Fluid samples of 47 cysts obtained by EUS-FNA over a 39-month period were analyzed. Mutation analysis of KRAS (exon 2) was performed in all cases, and additionally, GNAS (exon 8) in 28 cases using Sanger sequencing. Results: 33 out of 47 PCLs were classified as mucinous cysts and 14 as non-mucinous cysts defined using conventional standards, including morphological characteristics, string-sign, cytology, cyst fluid testing, and histology in resected cases. Of these 33 mucinous cysts, KRAS mutation was detected in 14 samples. A further 23 mucinous lesions were additionally tested for GNAS mutation, which was detected in 10 of the 23 cysts. A 42.4% sensitivity for KRAS and 43.5% for GNAS mutation analysis was calculated, with a specificity of 92.9% and 100%, respectively, for detecting mucinous lesions. The clinical management was altered through the genetic testing results in one single case. Conclusions: In this cohort, K-RAS and GNAS mutational analysis in cyst fluid did not improve the detection of mucinous pancreatic cysts significantly after conventional testing. However, the method may be useful due to its high specificity in uncertain cases. Full article

Background and Aims: Solid pseudopapillary neoplasms (SPN) are rare neoplasms of the pancreatic gland. Despite the indolent behavior, surgical resection is required according to the risk of metastasis development. Few data are available on endoscopic ultrasound (EUS) features, comparison between the features described at EUS and contrast-enhanced, and diagnostic accuracy and safety of EUS-guided FNB in these tumors. Patients and Methods: All consecutive patients with a EUS-guided FNB-based pathological diagnosis of SPN were extrapolated from a prospectively maintained database. Demographic, radiologic, and echo-endoscopic features were collected. FNB specimens were re-evaluated from two expert pathologist and the main histological features of SPN were investigated. Results: Thirty-seven patients were included (32 females and 5 males), with a mean age of 35.8 ± 15.8 years. Contrast-enhanced imaging based diagnosis was accurate in 20 patients (54.1%). EUS features were significantly different compared to contrast-enhanced imaging in terms of cystic appearance (40.5% vs. 16.2%; p = 0.03) and vascular pattern (p = 0.01). FNB-based diagnosis of SPN was confirmed on surgical specimen in all, 37 patients, resulting in a diagnostic accuracy of EUS-guided FNB of 100%. Only one patient (2.6%) experienced a mild procedure-related adverse event. Discussion: Contrast-enhanced imaging based diagnosis of SPN is difficult. Despite the rarity of the disease, EUS-guided FNB with 22-gauge fork-tip needle has a very high diagnostic accuracy for SPN, with rare and mild adverse events. Full article

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that frequently presents at an advanced stage with limited effective treatment options and a dismal prognosis. It is a highly heterogenous disease driven by various genetic and epigenetic alterations. Recent advances in sequencing modalities have significantly improved our understanding of the genetics of PDAC, which could lead to promising and novel therapeutic strategies. In this review, we summarize the most up-to-date literature on the molecular landscape of PDAC and its precursor lesions, as well as recent advances in targeted therapy. Full article

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 accurate classification of pancreatic cystic lesions remains clinically challenging due to overlapping imaging features and variable malignant potential. Mucinous cystic neoplasms, in particular, require early identification given their premalignant nature. RNA profiling presents a promising alternative to current diagnostic limitations—a molecular lens sharpened by AI-driven pattern recognition. This study aimed to evaluate the diagnostic potential of RNA signatures for differentiating pancreatic cyst subtypes and to clarify their roles in their pathophysiology. The study included 31 patients with pancreatic lesions who underwent endoscopic ultrasound-guided fine-needle aspiration. RNA was extracted from cyst fluid, tissue, and peripheral blood. Expression of 17 target genes was analyzed using qPCR. Gene expression patterns were compared across mucinous cystic neoplasms, serous cystic neoplasms, pseudocysts, adenocarcinoma, and chronic pancreatitis cohorts. Diagnostic accuracy was evaluated via ROC analysis. Mucinous cysts exhibited significant overexpression of MUC1, ITGA2, ELOVL6, and MUC5AC genes compared to serous cysts and pseudocysts. PKM gene expression correlated with increasing malignant potential. In blood plasma, only MUC1, MUC4, and PYGL were elevated in adenocarcinoma compared to mucinous neoplasms. We identified a distinct RNA signature that can distinguish mucinous cystic neoplasms from benign cystic lesions (serous cysts and pseudocysts), which could be useful for guiding patient management and improving clinical outcomes. Validation in broader cohorts is essential for clinical implementation. 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

The recommended surgery for pancreatic tumors is dependent on the diagnosis. For pancreatic adenocarcinoma, duodenal, and ampullary adenocarcinoma, a Whipple pancreaticoduodenectomy with lymph node dissection is recommended. For small < 2 cm or non-imageable gastrinomas, duodenal transillumination, duodenotomy, duodenal tumor excision and adjacent lymphadenectomy is recommended. For large > 3 cm gastrinomas, a Whipple pancreaticoduodenectomy with adjacent lymph node dissection is recommended. For small 1–2 cm insulinomas, intraoperative ultrasound with enucleation is recommended. If the patient with gastrinoma, insulinoma, or multiple nonfunctional NETs occurs in the setting of MEN-1, a subtotal pancreatectomy with or without splenectomy with enucleation of pancreatic head tumors is recommended, with adjacent lymph node dissection. The detail of each procedure is described with illustrations. 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

Endometriosis is a clinical entity affecting up to 10% of women of reproductive age, characterized by ectopic endometrial tissue outside the uterine cavity. While extrapelvic endometriosis has been documented, pancreatic endometriosis remains extremely rare and poses significant diagnostic challenges due to its similarity to other pancreatic diseases. At the same time, splenic mesothelial cysts are also rare and typically benign. This report presents a unique case of pancreatic endometriosis coexisting with a splenic mesothelial cyst in a 31-year-old woman. The patient presented to the emergency department with complaints of persistent epigastric and low back pain. She noted having similar symptoms approximately a year prior. Her past medical history was otherwise unremarkable, and there was no known family history of pancreatic disease or neoplasms. Initial imaging revealed a 3.8 cm cystic lesion in the pancreatic tail, with features suggestive of mucinous cystadenoma. Following clinical evaluation and confirmation of the cyst’s nature through endoscopic ultrasound-guided biopsy, the patient subsequently underwent laparoscopic distal pancreatectomy and splenectomy due to worsening symptoms. Gross examination revealed a multilocular pancreatic cyst with a smooth, hemorrhagic wall. Microscopic analysis showed the cyst to be lined by cuboidal to columnar epithelium, consistent with pancreatic endometriosis, confirmed by immunohistochemical staining. The spleen showed cystic formations, diagnosed as a multifaceted mesothelial cyst. In conclusion, this report is the first to document the coexistence of pancreatic endometriosis and splenic mesothelial cysts, highlighting the importance of accurate imaging and pathologic evaluation in the diagnosis of these rare conditions. Early diagnosis and surgical intervention lead to favorable outcomes, reinforcing the importance of comprehensive diagnostic strategies. Full article

Cystic mucinous neoplasms (MCNs) of the pancreas are rare cystic tumors, accounting for approximately 2–5% of all pancreatic neoplasms. They predominantly occur in premenopausal women and are typically located in the body or tail of the pancreas. Due to their potential for malignant transformation, especially in cases associated with invasive carcinoma such as pancreatic ductal adenocarcinoma, early detection, complete surgical resection, and rigorous postoperative surveillance are essential. The occurrence of MCNs in male patients is exceedingly rare, comprising only about 2% of reported cases, and often resulting in preoperative diagnostic challenges. Molecular analyses have identified a strong association between KRAS mutations and disease progression in MCNs, underscoring their potential role as prognostic markers despite limited diagnostic utility. In this report, we present two additional cases of MCNs in male patients, highlighting their histopathological features and the ancillary investigations undertaken to support diagnosis. 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: Pancreatic neuroendocrine neoplasms (PNENs) are rare but clinically significant tumors with variable radiological presentations that complicate diagnosis. While typical PNENs are well characterized, atypical features, such as cystic or hypoenhancing patterns, are less understood and can lead to diagnostic delays or misdiagnosis. This study aimed to evaluate atypical radiological presentations of PNENs, focusing on their impact on diagnostic pathways and differentiation from other pancreatic pathologies. Methods: A retrospective review was conducted of all PNEN cases diagnosed at a single tertiary center between 2010 and 2020. Cases with histopathological confirmation and available cross-sectional imaging were included. Radiological features were categorized as typical (solid and hyperenhancing) or atypical (cystic and hypoenhancing). Demographic, radiological, and pathological data were analyzed. Comparisons between typical and atypical PNENs were performed using descriptive and inferential statistics. Results: Among 77 PNEN cases, 39 met the inclusion criteria. Atypical radiological presentations were identified in 46% of cases, including cystic (18%) and hypoenhancing (28%) lesions. Hypoenhancing PNENs were significantly more likely to present with advanced disease (54% vs. 14% in typical PNENs, p = 0.016). In contrast, none of the cystic PNENs exhibited advanced disease. Atypical PNENs posed greater diagnostic challenges, with alternative diagnoses initially considered in 64% of hypoenhancing and 43% of cystic cases compared to 10% of typical PNENs (p = 0.0042). Conclusions: Atypical PNENs, particularly hypoenhancing lesions, present significant diagnostic challenges and are more likely to be associated with advanced disease. These findings highlight the need for improved recognition of atypical imaging patterns and more precise diagnostic strategies. However, the retrospective design and small cohort size limit the generalizability of our findings. Further multicenter studies are warranted to refine the imaging criteria and optimize the differentiation from other pancreatic neoplasms. 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