Pancreatic Cyst

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three years between the development of high-grade dysplasia and pancreatic cancer. Taken together, these data establish non-invasive IPMNs and MCNs as origins of invasive pancreatic cancer, identifying potential drivers of invasion, highlighting the complex clonal dynamics prior to malignant transformation, and providing opportunities for early detection and intervention.

BackgroundIt is clear that specific intestinal bacteria are involved in the development of different premalignant conditions along the gastrointestinal tract. An analysis of the microbial constituents in the context of pancreatic cystic lesions has, however, as yet not been performed. This consideration prompted us to explore whether endoscopically obtained pancreatic cyst fluids (PCF) contain bacterial DNA and to determine the genera of bacteria present in such material.MethodsTotal DNA was isolated from 69 PCF samples. Bacterial 16S rRNA gene-specific PCR was performed followed by Sanger sequencing and de novo deep sequencing for the V3-V4 variable region of 16S rRNA gene.ResultsWe observed that 98.2% of the samples were positive in conventional PCR, and that 100% of selected PCF samples (n = 33) were positive for bacterial microbiota as determined by next generation sequencing (NGS). Comprehensive NGS data analysis of PCF showed the presence of 408 genera of bacteria, of which 17 bacterial genera were uniquely abundant to PCF, when compared to the Human Microbiome Project (HMP) database and 15 bacterial microbiota were uniquely abundant in HMP only. Bacteroides spp., Escherichia/Shigella spp., and Acidaminococcus spp. which were predominant in PCF, while also a substantial Staphylococcus spp. and Fusobacterium spp. component was detected.ConclusionThese results reveal and characterize an apparently specific bacterial ecosystem in pancreatic cyst fluid samples and may reflect the local microbiota in the pancreas. Some taxa with potential deleterious functions are present in the bacterial abundance profiles, suggesting that the unique microbiome in this specific niche may contribute to neoplastic processes in the pancreas. Further studies are needed to explore the intricate relationship between pathophysiological status in the host pancreas and its microbiota.

Pancreatic cystic lesions (PCL) are increasingly diagnosed. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) cytology is often used for diagnostic confirmation but can be inconclusive. In this study, the role of molecular analyses in the pre-operative diagnostics of PCL is evaluated. Targeted Next Generation Sequencing (NGS) applied on cytology smears was retrospectively evaluated in a cohort of 37 resected PCL. Usefulness of NGS on fresh cyst fluids was tested in a prospective cohort of patients with newly diagnosed PCL (n = 71). In the retrospective cohort, cytology plus NGS displayed higher sensitivity (94.1% vs. 87.1%) and specificity (100% vs. 50%) than cytology alone for the detection of mucinous neoplasms. In the prospective cohort, sensitivity and specificity of conventional cytology alone were 54.2% and 100% for the detection of mucinous neoplasia and 50.0% and 100% for the detection of high-grade dysplasia, respectively. Adding NGS, all lesions which underwent histopathologic verification (12/71, 17%) could be classified without false positive or false negative results regarding the detection of mucinous neoplasm so far. NGS analysis of cfDNA in PCL fluids is feasible and can increase diagnostic accuracy in the detection of mucinous neoplasms compared to cytology alone. However, algorithms for the detection of high-risk lesions need further improvement.

ImportanceSubsets of pancreatic cystic lesions (PCLs) are the only radiographically evident precursors to pancreatic cancer. Guidelines prioritize cyst size and high-risk features to determine the need for resection. However, the true prevalence of PCLs and risk factors for their development in the general population remain unknown, as available data are often biased by imaging performed in symptomatic patients.ObjectiveTo determine prevalence of PCLs in an asymptomatic North American cohort using size-based risk categorization and identify associated demographic factors and exposures.Design, setting, participantsThis cross-sectional study included asymptomatic individuals who underwent rapid whole-body magnetic resonance imaging using a commercially available 1.5T device for general preventive screening between January 1, 2020, and May 31, 2023. Scans were interpreted by certified radiologists using standardized synoptic reporting templates. Diagnostic free-text reports were analyzed, and positive reports underwent independent additional review. Data were analyzed from February 4, 2024, to March 6, 2025.ExposuresParticipant demographic information and lifestyle exposures.Main outcomes and measuresPrevalence of PCLs based on size-based risk categorization.ResultsAmong 21 651 individuals undergoing screening MRI (11 050 [51.0%] male; median age, 51 [IQR, 42-61] years), 1509 (7.0%) had an incidental PCL (776 [51.4%] female), and age- and sex-standardized prevalence was 6.3%. The median age was higher in individuals with PCLs (61 [IQR, 51-69] vs 50 [IQR, 41-60] years). Prevalence increased with age, from 86 of 4223 (2.0%) 39 years or younger to 229 of 5720 (4.0%) aged 40 to 49 years, 390 of 5586 (7.0%) aged 50 to 59 years, 467 of 4049 (11.5%) aged 60 to 65 years, 268 of 1741 (15.4%) aged 70 to 79 years, and 69 of 332 (20.8%) 80 years or older (P Conclusions and relevanceIn this cross-sectional study of 21 651 individuals, incidental PCLs were common (6.3%) and found in as many as 20.8% of older individuals undergoing whole-body MRI screening, with 1492 PCLs (98.9%) of all PCLs being less than 3 cm.