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Background/objectives: Pancreatic cyst management can be distilled into three separate pathways - discharge, monitoring or surgery- based on the risk of malignant transformation. This study compares the performance of artificial intelligence (AI) models to clinical care for this task., Methods: Two explainable boosting machine (EBM) models were developed and evaluated using clinical features only, or clinical features and cyst fluid molecular markers (CFMM) using a publicly available dataset, consisting of 850 cases (median age 64; 65 % female) with independent training (429 cases) and holdout test cohorts (421 cases). There were 137 cysts with no malignant potential, 114 malignant cysts, and 599 IPMNs and MCNs., Results: The EBM and EBM with CFMM models had higher accuracy for identifying patients requiring monitoring (0.88 and 0.82) and surgery (0.66 and 0.82) respectively compared with current clinical care (0.62 and 0.58). For discharge, the EBM with CFMM model had a higher accuracy (0.91) than either the EBM model (0.84) or current clinical care (0.86). In the cohort of patients who underwent surgical resection, use of the EBM-CFMM model would have decreased the number of unnecessary surgeries by 59 % (n = 92), increased correct surgeries by 7.5 % (n = 11), identified patients who require monitoring by 122 % (n = 76), and increased the number of patients correctly classified for discharge by 138 % (n = 18) compared to clinical care., Conclusions: EBM models had greater sensitivity and specificity for identifying the correct management compared with either clinical management or previous AI models. The model predictions are demonstrated to be interpretable by clinicians., Competing Interests: Declaration of competing interest E.K.F. has educational grant support with GE Medical, Siemens Healthineers research grant support, HipGraphics Inc (co-founder and shareholder), Exact Sciences (consultant), Imaging Endpoints (consultant). A.M.L. is a consultant with Exact Sciences. K.W.K. is also a member of the Scientific Advisory Boards of Eisai-Morphotek, Syxmex-Inostics, CAGE, and NeoPhore. These companies, as well as other companies, have licensed technologies from Johns Hopkins University, on which K.W.K. is an inventor. These licenses and relationships are associated with equity or royalty payments to K.W.K. The terms of these arrangements are being managed by Johns Hopkins University in accordance with its conflict of interest policies. D.S.K. is a consultant and equity holder in PAIGE. AI. The terms of all these arrangements are being managed by Johns Hopkins University in accordance with its conflict of interest policies. The following patents are related to this work: Safe Sequencing System US201161476150P, Rapid Aneuploidy Detection US201261615535P, Mutations in pancreatic neoplasms US9976184B2, and Differential identification of pancreatic cysts US9637796B2., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Pancreatic Cystic Neoplasms (PCN) represent a diverse group of tumors, some of which may progress to pancreatic cancer. Considering their high prevalence in the general population, the development of reliable biomarkers is crucial. The ideal biomarker will accurately diagnose the subtype of PCN and assess the risk of high-grade dysplasia or invasive cancer. Cyst fluid analysis has emerged as a promising approach to accomplish this goal, yet no single marker has yet gained unanimous support for routine inclusion in PCN evaluation., Competing Interests: Disclosure A.V. Maker is an inventor of record on the following pending or issued patent: WO2018183603A1 (PCT/US2018/025,027). T. Pollini and L. Todeschini have no conflict of interest. Funding Authors acknowledge the support of the Inner Child Foundation and the Shorenstein Foundation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

There is increasing evidence that the secretory/excretory antigens of the larval stage of Echinococcus granulosus can induce both anticancer and oncogenic effects between parasite-derived metabolites and various cancer cells. The dual role of miR-145 as either a tumor suppressor or oncogene has already been reported in cancer. However, the mechanism by which miR-145 induces apoptosis in lung cancer cells treated with hydatid cyst fluid (HCF) remains unclear. The fertile HCF was obtained from sheep, purified and lyophilized. H1299 human lung cancer cells were then cultured into two groups: HCF-treated H1299 lung cancer cells and untreated H1299 cancer cells as control cells. Cell viability was assessed using MTT assay to evaluate the effects of HCF on the H1299 cells. Caspase-3 activity was assessed by fluorometric assay. In addition, mRNA expression levels of VGEF, vimentin, caspase-3, miRNA-145, Bax and Bcl-2 genes were quantified by real-time PCR. A scratch test was also performed to assess the effects of HCF on cell migration. The MTT assay revealed that the growth of H1299 cells increased when treated with 60 μg/mL of fertile HCF for 24 h. The fold change of caspase-3, miRNA-145, Bax/Bcl-2 ratio and caspase-3 activity was lower in HCF-treated H1299 cells compared to the control cell. The fold change in VGEF and vimentin gene expression was higher in the HCF-treated H1299 cells than in the control cell. The scratch test results showed that H1299 cell mobility increased 24 and 48 h after exposure to HCF. Our results suggest that the downregulation of miR-145 in HCF-treated H1299 cells may play a role as a possible oncogenic regulator of lung cancer growth. To confirm this assumption, further studies are required to evaluate the microRNA profile and effective oncogenes in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Distinguishing mucinous (M) pancreatic cystic neoplasms (PCNs) from non-mucinous (NM) is challenging but crucial. Low intracystic glucose level has shown diagnostic tool promise, however further investigation is needed to understand metabolic processes., Aims: To compare the diagnostic accuracy of intracystic glucose and CEA levels in a large cohort and explore lactate levels as potential marker., Methods: PCNs≥15 mm which underwent EUS-fine needle aspiration were prospectively enrolled. Glucose, CEA and lactate levels were measured. Diagnostic accuracy for M-PCN diagnosis was evaluated using surgical/cytology reports or multidisciplinary evaluations., Results: 169 PCNs were included (64 % M-PCNs). Median intracystic glucose was significantly lower in M-PCNs (1 mg/dL) compared to NM-PCNs (101 mg/dL); mean intracystic CEA was significantly higher in M-PCNs (152.5 ng/mL) compared to NM-PCNs (0.3 ng/mL). ROC curve analysis revealed best glucose cut-off ≤58 mg/dL (accuracy 93.5 %) and CEA cut-off >2.5 ng/mL (accuracy 90.5 %) for M-PCNs. Intracystic lactates were significantly lower in M-PCNs correlating directly with glucose. Single glucose dosage evidenced best diagnostic accuracy respect markers combination., Conclusion: Intracystic glucose demonstrated high diagnostic utility for M-PCNs differentiation, surpassing CEA. Lactate levels correlated with glucose, suggesting their uptake by M-PCNs cells. These findings contribute to a better metabolic landscape understanding glucose use as diagnostic marker., Competing Interests: Conflict of interest None., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: Elevated pancreatic cyst fluid carcinoembryonic antigen (CEA) has been routinely used to classify mucinous cysts. This study incorporates original data that established the CEA ≥192 ng/mL threshold with over 20 years of additional data and reassesses the diagnostic performance of CEA for differentiating mucinous from non-mucinous cysts., Design: 1169 pancreatic cysts (1999-2021) with CEA results were identified. 394 cases had histological confirmation as the diagnostic standard. Additionally, 237 cysts without histological confirmation demonstrated KRAS , GNAS , or RNF43 mutations by molecular testing and were combined with the histologically confirmed cysts for separate analysis on a total cohort of 631 cysts., Results: Median CEA was significantly higher in mucinous cysts (323.9 ng/mL, n=314) versus non-mucinous cysts (204.6 ng/mL, n=80) (p<0.001). Receiver operating characteristic curve analysis demonstrated an optimal CEA cut-off of 20 ng/mL (area under the curve: 80%), though the specificity was lower than desired (sensitivity 89%, specificity 64%). At the previously established threshold of 192 ng/mL, sensitivity and specificity were 56% and 78%, respectively. To achieve a specificity of 85% as originally reported, a CEA threshold of 250 ng/mL was needed; the 13 false positive cases at this threshold included 4 benign simple cysts, 2 squamoid cysts, 1 serous cystadenoma, 1 lymphoepithelial cyst and 5 more uncommon entities. All results remained similar within the total cohort after including additional cases with KRAS/GNAS/RNF43 mutations only., Conclusion: Cyst fluid CEA continues to be a useful test in the diagnosis of mucinous pancreatic cysts but does not appear as specific as previously reported. Raising the CEA threshold to 250 ng/mL to maintain specificity for differentiating mucinous from non-mucinous cysts may be considered., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Cystic Echinococcosis (CE) is a zoonotic infection caused by the larval form of Echinococcus granulosus in humans. Emerging evidence suggests an intriguing inverse association between E. granulosus infection and the occurrence of cancer. This study aimed to investigate the influence of diverse host-derived hydatid cyst fluids (HCF) with distinct genotypes on human liver hepatocytes (HC) and hepatocellular carcinoma cells (HepG2). Specifically, we examined their effects on cell proliferation, apoptosis sensitivity (BAX/BCL-2), apoptosis-related p53 expression, and the expression of cancer-related microRNA (hsa-miR-181b-3p). Cell proliferation assays, real-time PCR, and ELISA studies were conducted to evaluate potential anti-cancer properties. The findings revealed that animal-origin HCF (G1(A)) induced direct cell death by augmenting the susceptibility of HepG2 cells to apoptosis. Treatment with both G1(A) and G1(H) HCF sensitized HepG2 and HC cell lines to apoptosis by modulating the BAX/BCL-2 ratio, accompanied by upregulation of the p53 gene. Additionally, G1(A) HCF and human-derived HCFs (G1(H), G7(H)) reduced the expression of miR-181b-3p in HepG2 cells. Consequently, this study demonstrates the potential anti-cancer effect of HCF in HepG2 cells and provides the first comparative assessment of HCFs from human and animal sources with diverse genotypes, offering novel insights into this field., (© 2024. The Author(s).)

Introduction: Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by the metacestode of Echinococcus granulosus. CE is a health problem in Middle Eastern countries, such as Iran. The purpose of this study was to purify subunit 8 KDa antigen B from crude sheep hydatid cyst fluid (HCF) and compare its sensitivity and specificity with a commercial human ELISA kit (PT-Hydatid-96)., Methods: 28 sera samples were collected from hydatid cyst patients who had surgery for a hydatid cyst and had their disease confirmed by pathology after the surgery. Furthermore, 35 samples of healthy individuals with no history of hydatid cysts were collected, as were nine serum samples from parasite-infected non-CE patients. HCF was obtained from sheep fertile cysts at a Sari slaughterhouse and used as an antigen. In an indirect ELISA test, the B antigen was employed, and the results were compared to those from a commercial ELISA kit., Results: The results of this study were analyzed using the Kappa test. The commercial ELISA kit showed 17 cases (23.6%) positive, 44 cases (61.1%) negative, and 11 cases (15.3%) borderline. B antigen showed that 18 (25%), 43 (59.7 %), and 11 (15.3%) were positive, negative, and borderline, respectively. One sample (1.4% of 72 total samples) of 35 serum samples from healthy individuals was positive using B antigen-based ELISA. In addition, all nine serum samples from parasite-infected non-CE patients were negative for both tests. The sensitivity and specificity of the commercial ELISA kit have been evaluated at 60.7% and 100%, respectively. For B antigenbased ELISA, these values are 64.3 and 97.7%, respectively., Conclusion: Antigen B produced from hydatid cyst fluid is a promising option for serological identification of hydatid cysts in both infected and healthy individuals. In an indirect ELISA test, hydatid fluid antigen could be used as a precise source of detection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)