{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:59:43Z","timestamp":1792789183087,"version":"4.5.0"},"reference-count":62,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["JP23K14582"],"award-info":[{"award-number":["JP23K14582"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tokyo Metropolitan Hospital Clinical Research Project Fund","award":["R050403006"],"award-info":[{"award-number":["R050403006"]}]},{"name":"Pancreas Research Foundation of Japan","id":[{"id":"https:\/\/ror.org\/05m62xk31","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/05m62xk31","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Treatment for pancreatic ductal adenocarcinoma (PDAC) depends on early detection, yet most present at an inoperable stage. Focal pancreatic parenchymal atrophy (FPPA) is a prodromal imaging feature lacking objective quantification. We evaluated whether longitudinal, AI-measured pancreatic volume (PV) change is associated with subsequent PDAC. Methods: In this retrospective case\u2013control study, we analyzed longitudinal CT from 40 PDAC patients and 61 controls, each with \u22655 years of pre-index imaging. PV was measured by AI segmentation and compared as a subject-specific rate of change, with robustness assessed via multivariable, mixed-effects, and sensitivity analyses. Results: PDAC patients showed more rapid PV decline than matched controls (5-year reduction 9.71 vs. 1.23 mL; p = 0.013), persisting after excluding diabetes and adjustment. A mixed-effects model confirmed faster decline, consistent across truncation windows but absent near diagnosis. Adding the marker to a basic covariate model raised the area under the curve (AUC) from 0.679 to 0.823. Exploratory transcriptomic profiling of microdissected FPPA identified 131 concordantly altered genes across PanIN- and invasive-PDAC-adjacent comparisons, with an immune-related signal present adjacent to non-invasive PanIN and larger adjacent to invasive PDAC. Conclusions: Patients who later developed PDAC showed greater long-term PV decline than controls. Exploratory tissue profiling raises the hypothesis that the same process underlying FPPA may also contribute to PV loss. Because the imaging and molecular analyses only partially overlapped and included no within-patient imaging\u2013transcriptomic correlation, the proposed tissue-level correlate remains an unproven hypothesis requiring same-patient validation. This marker requires validation before use as a risk-enrichment signal, not a screening test.<\/jats:p>","DOI":"10.3390\/cancers18183062","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:50:03Z","timestamp":1789995003000},"page":"3062","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Accelerated Pancreatic Volume Loss as a Potential Pre-Diagnostic Imaging Biomarker for Pancreatic Cancer Risk Enrichment: An AI-Assisted Volumetric Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1434-3410","authenticated-orcid":false,"given":"Jun","family":"Nakahodo","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo 113-8677, Japan"},{"name":"Department of Human Pathology, Juntendo University, Bunkyo-ku, Tokyo 113-8431, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Wataru","family":"Ujita","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo 113-8677, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3873-8268","authenticated-orcid":false,"given":"Daichi","family":"Sadato","sequence":"additional","affiliation":[{"name":"Clinical Research and Trials Center, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo 113-8677, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7702-6634","authenticated-orcid":false,"given":"Yuki","family":"Fukumura","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, Juntendo University, Bunkyo-ku, Tokyo 113-8431, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Yuji","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, Juntendo University, Bunkyo-ku, Tokyo 113-8431, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Masataka","family":"Kikuyama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tokyo Women\u2019s Medical University Hospital, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Shin-ichiro","family":"Horiguchi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo 113-8677, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Mizuka","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo 113-8677, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Kazuro","family":"Chiba","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo 113-8677, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Hiroki","family":"Tabata","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo 113-8677, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3946-6401","authenticated-orcid":false,"given":"Kensuke","family":"Hoshi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo 113-8677, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4284-9574","authenticated-orcid":false,"given":"Ryogo","family":"Minami","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo 113-8677, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0918-6270","authenticated-orcid":false,"given":"Toshiro","family":"Iizuka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo 113-8677, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Terumi","family":"Kamisawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo 113-8677, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1273-9051","authenticated-orcid":false,"given":"Masanao","family":"Kurata","sequence":"additional","affiliation":[{"name":"Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo 113-8677, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1488-9958","authenticated-orcid":false,"given":"Masakazu","family":"Toi","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo 113-8677, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref_1","unstructured":"National Cancer Institute (2026, August 16). SEER Cancer Stat Facts: Pancreatic Cancer, Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/pancreas.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1200\/JCO.22.00298","article-title":"The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival","volume":"40","author":"Dbouk","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1053\/j.gastro.2023.02.012","article-title":"Pancreatic Cancer: Changing Epidemiology and New Approaches to Risk Assessment, Early Detection, and Prevention","volume":"164","author":"Stoffel","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s11938-025-00480-w","article-title":"Early Detection of Pancreatic Cancer: Recent Advancements","volume":"23","author":"Konikoff","year":"2025","journal-title":"Curr. Treat. Options Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.dld.2026.03.002","article-title":"Liquid Biopsy in Pancreatic Cancer: Current Advances, Limitations, and Future Perspectives","volume":"58","author":"Carrara","year":"2026","journal-title":"Dig. Liver Dis."},{"key":"ref_6","first-page":"375","article-title":"Multidisciplinary Standards of Care and Recent Progress in Pancreatic Ductal Adenocarcinoma","volume":"70","author":"Grossberg","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1001\/jama.2019.9690","article-title":"Screening for Pancreatic Cancer","volume":"322","author":"Lucas","year":"2019","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1038\/clpt.2010.233","article-title":"Enrichment of Clinical Study Populations","volume":"88","author":"Temple","year":"2010","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1177\/1740774517723588","article-title":"Evaluating Biomarkers for Prognostic Enrichment of Clinical Trials","volume":"14","author":"Kerr","year":"2017","journal-title":"Clin. Trials"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.2214\/AJR.21.26014","article-title":"CT Abnormalities of the Pancreas Associated with the Subsequent Diagnosis of Clinical Stage I Pancreatic Ductal Adenocarcinoma More Than 1 Year Later: A Case-Control Study","volume":"217","author":"Toshima","year":"2021","journal-title":"Am. J. Roentgenol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Miura, S., Takikawa, T., Kikuta, K., Hamada, S., Kume, K., Yoshida, N., Tanaka, Y., Matsumoto, R., Ikeda, M., and Kataoka, F. (2021). Focal Parenchymal Atrophy of the Pancreas Is Frequently Observed on Pre-Diagnostic Computed Tomography in Patients with Pancreatic Cancer: A Case-Control Study. Diagnostics, 11.","DOI":"10.3390\/diagnostics11091693"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/j.pan.2022.10.003","article-title":"Focal Pancreatic Parenchyma Atrophy Is a Harbinger of Pancreatic Cancer and a Clue to the Intraductal Spreading Subtype","volume":"22","author":"Nakahodo","year":"2022","journal-title":"Pancreatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1002\/ueg2.12557","article-title":"Temporal Progression of Pancreatic Cancer Computed Tomography Findings until Diagnosis: A Large-Scale Multicenter Study","volume":"12","author":"Gonda","year":"2024","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1007\/s12328-025-02158-3","article-title":"Carcinoma in Situ of the Pancreas Detected by Progressive Focal Pancreatic Parenchymal Atrophy without Main Pancreatic Ductal Change","volume":"18","author":"Nishiyama","year":"2025","journal-title":"Clin. J. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.pan.2017.11.007","article-title":"Multicenter Study of Early Pancreatic Cancer in Japan","volume":"18","author":"Kanno","year":"2018","journal-title":"Pancreatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1016\/j.pan.2020.09.020","article-title":"Focal Parenchymal Atrophy of Pancreas: An Important Sign of Underlying High-Grade Pancreatic Intraepithelial Neoplasia without Invasive Carcinoma, i.e., Carcinoma in Situ","volume":"20","author":"Nakahodo","year":"2020","journal-title":"Pancreatology"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sagami, R., Yamao, K., Nakahodo, J., Minami, R., Tsurusaki, M., Murakami, K., and Amano, Y. (2021). Pre-Operative Imaging and Pathological Diagnosis of Localized High-Grade Pancreatic Intra-Epithelial Neoplasia without Invasive Carcinoma. Cancers, 13.","DOI":"10.3390\/cancers13050945"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/jgh3.12930","article-title":"Diffuse Pancreatic Parenchymal Atrophy, an Imaging Finding Predictive of the Development of Pancreatic Ductal Adenocarcinoma: A Case-Control Study","volume":"7","author":"Koiwai","year":"2023","journal-title":"JGH Open"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1002\/ags3.70230","article-title":"Pancreatic Atrophy: A Narrative Review and Surgical Interpretation","volume":"10","author":"Fujino","year":"2026","journal-title":"Ann. Gastroenterol. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1093\/carcin\/bgae064","article-title":"From Precursor to Cancer: Decoding the Intrinsic and Extrinsic Pathways of Pancreatic Intraepithelial Neoplasia Progression","volume":"45","author":"Graham","year":"2024","journal-title":"Carcinogenesis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"626","DOI":"10.2958\/suizo.30.626","article-title":"Three Cases of Pancreatic Intraepithelial Neoplasia with Marked Pancreatic Body Lipomatosis Confirmed on CT","volume":"30","author":"Kikuyama","year":"2015","journal-title":"Suizo"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1620\/tjem.252.63","article-title":"Focal Parenchymal Atrophy and Fat Replacement Are Clues for Early Diagnosis of Pancreatic Cancer with Abnormalities of the Main Pancreatic Duct","volume":"252","author":"Miura","year":"2020","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Yamao, K., Takenaka, M., Ishikawa, R., Okamoto, A., Yamazaki, T., Nakai, A., Omoto, S., Kamata, K., Minaga, K., and Matsumoto, I. (2020). Partial Pancreatic Parenchymal Atrophy Is a New Specific Finding to Diagnose Small Pancreatic Cancer (\u226410 mm) Including Carcinoma in Situ: Comparison with Localized Benign Main Pancreatic Duct Stenosis Patients. Diagnostics, 10.","DOI":"10.3390\/diagnostics10070445"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1007\/s00535-024-02149-0","article-title":"Association of Pancreatic Atrophy Patterns with Intraductal Extension of Early Pancreatic Ductal Adenocarcinoma: A Multicenter Retrospective Study","volume":"59","author":"Miki","year":"2024","journal-title":"J. Gastroenterol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.pan.2025.01.003","article-title":"Focal Pancreatic Parenchymal Atrophy Could Be a Precursor of Pancreatic Cancer","volume":"25","author":"Kikuyama","year":"2025","journal-title":"Pancreatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1007\/s12328-026-02326-z","article-title":"Extensive High-Grade PanIN of the Main Pancreatic Duct Requiring Total Pancreatectomy Diagnosed after Long-Term Surveillance","volume":"19","author":"Yaguchi","year":"2026","journal-title":"Clin. J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s12065-026-01202-6","article-title":"Artificial Intelligence for Early Detection of Pancreatic Cancer: Pre-Diagnostic Detection across Imaging, Biomarkers, and EHRs: A Systematic Review","volume":"19","author":"Apostolou","year":"2026","journal-title":"Evol. Intell."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/ncb3513","article-title":"The EMT-Activator Zeb1 Is a Key Factor for Cell Plasticity and Promotes Metastasis in Pancreatic Cancer","volume":"19","author":"Krebs","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.cell.2011.11.025","article-title":"EMT and Dissemination Precede Pancreatic Tumor Formation","volume":"148","author":"Rhim","year":"2012","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8307","DOI":"10.1038\/s41467-025-63864-7","article-title":"An Injury-Associated Lobular Microniche Is Associated with the Classical Tumor Cell Phenotype in Pancreatic Cancer","volume":"16","author":"Viljamaa","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Miyamoto, R., Takahashi, A., Ogasawara, A., Ogura, T., Kitamura, K., Ishida, H., Matsudaira, S., Nozu, S., and Kawashima, Y. (2022). Three-dimensional simulation of the pancreatic parenchyma, pancreatic duct and vascular arrangement in pancreatic surgery using a deep learning algorithm. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0276600"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ali, T., Masood, K., Irfan, M., Draz, U., Nagra, A.A., Asif, M., Alshehri, B.M., Glowacz, A., Tadeusiewicz, R., and Mahnashi, M.H. (2020). Multistage Segmentation of Prostate Cancer Tissues Using Sample Entropy Texture Analysis. Entropy, 22.","DOI":"10.3390\/e22121370"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1214\/aos\/1013699998","article-title":"The Control of the False Discovery Rate in Multiple Testing under Dependency","volume":"29","author":"Benjamini","year":"2001","journal-title":"Ann. Stat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"963","DOI":"10.2307\/2529876","article-title":"Random-Effects Models for Longitudinal Data","volume":"38","author":"Laird","year":"1982","journal-title":"Biometrics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1002\/(SICI)1097-0258(19960229)15:4<361::AID-SIM168>3.0.CO;2-4","article-title":"Multivariable Prognostic Models: Issues in Developing Models, Evaluating Assumptions and Adequacy, and Measuring and Reducing Errors","volume":"15","author":"Harrell","year":"1996","journal-title":"Stat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2307\/2531595","article-title":"Comparing the Areas under Two or More Correlated Receiver Operating Characteristic Curves: A Nonparametric Approach","volume":"44","author":"DeLong","year":"1988","journal-title":"Biometrics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1177\/0272989X06295361","article-title":"Decision Curve Analysis: A Novel Method for Evaluating Prediction Models","volume":"26","author":"Vickers","year":"2006","journal-title":"Med. Decis. Mak."},{"key":"ref_38","first-page":"38","article-title":"Chronic Pancreatitis, Obesity, and Pancreatic Cancer: Common Mechanisms of Development","volume":"2","author":"Christich","year":"2025","journal-title":"Visnyk Klubu Pankreatologiv"},{"key":"ref_39","first-page":"1","article-title":"New Onset Diabetes vs. Long-Standing Diabetes Pathogenesis about Pancreatic Cancer: A Narrative Review","volume":"2","author":"Tofaili","year":"2024","journal-title":"J. Endocrinol. Diabetes Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s13578-025-01474-y","article-title":"The Complex Interplay between Diabetes Mellitus and Pancreatic Carcinogenesis: Deciphering Multifactorial Mechanisms and Identifying Emerging Therapeutic Vulnerabilities","volume":"15","author":"Lu","year":"2025","journal-title":"Cell Biosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1900\/RDS.2016.13.132","article-title":"Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay between Endocrine and Exocrine Pancreas","volume":"13","author":"Saisho","year":"2016","journal-title":"Rev. Diabet. Stud."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e27096","DOI":"10.1097\/MD.0000000000027096","article-title":"Normal Pancreatic Volume Assessment Using Abdominal Computed Tomography Volumetry","volume":"100","author":"Li","year":"2021","journal-title":"Medicine"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1080\/17474124.2018.1496015","article-title":"Pancreas Volume in Health and Disease: A Systematic Review and Meta-Analysis","volume":"12","author":"DeSouza","year":"2018","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"321","DOI":"10.4258\/hir.2020.26.4.321","article-title":"Distribution and Characteristics of Pancreatic Volume Using Computed Tomography Volumetry","volume":"26","author":"Yoon","year":"2020","journal-title":"Healthc. Inform. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/nature19823","article-title":"A Renewed Model of Pancreatic Cancer Evolution Based on Genomic Rearrangement Patterns","volume":"538","author":"Notta","year":"2016","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1136\/gutjnl-2016-313317","article-title":"A Genetic Roadmap of Pancreatic Cancer: Still Evolving","volume":"66","author":"Notta","year":"2017","journal-title":"Gut"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41586-024-07359-3","article-title":"3D Genomic Mapping Reveals Multifocality of Human Pancreatic Precancers","volume":"629","author":"Braxton","year":"2024","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.cels.2024.07.001","article-title":"PanIN and CAF Transitions in Pancreatic Carcinogenesis Revealed with Spatial Data Integration","volume":"15","author":"Bell","year":"2024","journal-title":"Cell Syst."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Elhossiny, A.M., Kadiyala, P., Okoye, J.O., Hiraki, H.L., Procario, M.C., Giridharan, T., Watkoske, H.R., Ruckert, M.T., Wang, J., and Griffith, B.D. (2026). Asynchronous Evolution of Epithelium and Stroma Differentiates Precursor Lesions from Pancreatic Cancer. Cancer Discov., OF1\u2013OF25.","DOI":"10.1158\/2159-8290.CD-25-2001"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.ccr.2012.04.024","article-title":"Oncogenic Kras-Induced GM-CSF Production Promotes the Development of Pancreatic Neoplasia","volume":"21","author":"Lee","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1083\/jcb.201301001","article-title":"Macrophage-Secreted Cytokines Drive Pancreatic Acinar-to-Ductal Metaplasia through NF-\u03baB and MMPs","volume":"202","author":"Liou","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Mazej Jeram, N., Senjor, E., Kos, J., and Peri\u0161i\u0107 Nanut, M. (2026). The Lysosome\u2013Cathepsin Axis in Pancreatic Cancer: Mechanisms of Stromal Remodeling, Immune Evasion, and Therapy Resistance. Biomolecules, 16.","DOI":"10.20944\/preprints202604.1827.v1"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Zou, X., Guan, C., Gao, J., Shi, W., Cui, Y., and Zhong, X. (2023). Tertiary Lymphoid Structures in Pancreatic Cancer: A New Target for Immunotherapy. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1222719"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"102714","DOI":"10.1016\/j.ebiom.2020.102714","article-title":"Evolution of the Immune Landscape during Progression of Pancreatic Intraductal Papillary Mucinous Neoplasms to Invasive Cancer","volume":"54","author":"Roth","year":"2020","journal-title":"eBioMedicine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12943-018-0927-5","article-title":"Tumor-Stromal Crosstalk in Pancreatic Cancer and Tissue Fibrosis","volume":"18","author":"Thomas","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e191937","DOI":"10.1172\/JCI191937","article-title":"Early Neoplastic Lesions of the Pancreas: Initiation, Progression, and Opportunities for Precancer Interception","volume":"135","author":"Pedro","year":"2025","journal-title":"J. Clin. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1148\/radiol.211561","article-title":"Value-Added Opportunistic CT Screening: State of the Art","volume":"303","author":"Pickhardt","year":"2022","journal-title":"Radiology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1053\/j.gastro.2018.05.023","article-title":"Model to Determine Risk of Pancreatic Cancer in Patients with New-Onset Diabetes","volume":"155","author":"Sharma","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1080\/14737159.2025.2464563","article-title":"Decoding Pancreatic Cancer: Key Risk Factors across Genetics and Lifestyle","volume":"25","author":"Sharma","year":"2025","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1136\/gutjnl-2019-319352","article-title":"Management of Patients with Increased Risk for Familial Pancreatic Cancer: Updated Recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium","volume":"69","author":"Goggins","year":"2020","journal-title":"Gut"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Cammarata, R., La Vaccara, V., Bani, L., Giordano, F., Castagliuolo, P., Ristori, M.V., Aita, S.E., Angeletti, S., Coppola, R., and Caputo, D. (2026). Pancreatic Steatosis as a Risk Phenotype for Pancreatic Ductal Adenocarcinoma: A Narrative Review. Medicina, 62.","DOI":"10.3390\/medicina62040729"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1080\/00365521.2026.2632062","article-title":"Pancreatic Steatosis Is a Risk Factor for Pancreatic Cysts among Patients with Diabetes","volume":"61","author":"Johansson","year":"2026","journal-title":"Scand. J. Gastroenterol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/3062\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:15:38Z","timestamp":1790136938000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/3062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":62,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18183062"],"URL":"https:\/\/doi.org\/10.3390\/cancers18183062","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}