{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:18:05Z","timestamp":1788365885860,"version":"build-2803163510"},"reference-count":34,"publisher":"American Medical Association (AMA)","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Surg"],"abstract":"\n Importance<\/jats:title>\n Early liver metastasis (early-LiM) after pancreatectomy represents an aggressive biological phenotype of pancreatic ductal adenocarcinoma (PDAC) and is associated with markedly poor survival. Reliable preoperative biomarkers to identify occult hepatic micrometastasis remain lacking.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To develop and externally validate a circulating exosomal microRNA (exo-miRNA)\u2013based machine learning model for preoperative detection of occult early-LiM in PDAC.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This multicenter retrospective case-control study included 3 phases: genome-wide discovery using exo-miRNA sequencing (discovery cohort), model development (training cohort), and independent external validation (2 validation cohorts). The study took place at 4 medical centers in China, Japan, and South Korea. A total of 372 patients were enrolled between 2011 and 2024. Data were analyzed from July 2024 to November 2025.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Circulating plasma-derived exosomal miRNA expression profiles.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was early-LiM, defined as liver recurrence within 6 months after curative-intent resection. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and survival outcomes were assessed using Kaplan-Meier analysis.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 372 patients with PDAC (median [IQR] age, 67 [59-73] years; 229 [61.6%] male and 143 [38.4%] female; median follow-up among survivors, 969 days),early-LiM was associated with significantly worse overall survival compared with other recurrence patterns (median OS, 9.1 months vs 26.6-31.8 months; log-rank\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). A 7-exo-miRNA extreme gradient boosting model demonstrated discrimination in the training cohort (AUC, 0.899; 95% CI, 0.822-0.976) and maintained performance in external testing cohorts (AUC, 0.876; 95% CI, 0.846-0.951 and AUC, 0.862; 95% CI, 0.744-0.981). The exo-miRNA panel score remained an independent identifier of early-LiM in multivariable analysis (odds ratio, 26.49; 95% CI, 18.45-55.28;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001) and stratified overall survival (log-rank\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). Decision curve analysis suggested improved net clinical benefit compared with conventional clinicopathologic variables.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion and Relevance<\/jats:title>\n In this multicenter study, a circulating exo-miRNA\u2013based machine learning model enabled preoperative detection of occult early liver metastasis risk in PDAC. These findings support the potential of exosomal biomarkers to inform biology-guided treatment sequencing and warrant prospective validation.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamasurg.2026.3840","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:30:25Z","timestamp":1788363025000},"source":"Crossref","is-referenced-by-count":0,"title":["An Exosomal Signature for Preoperative Detection of Occult Liver Metastasis in Pancreatic Cancer"],"prefix":"10.1001","author":[{"given":"Takayuki","family":"Noma","sequence":"first","affiliation":[{"name":"Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, California"},{"name":"Department of Surgery, Tokushima University, Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyang","family":"Yin","sequence":"additional","affiliation":[{"name":"Institute of Hepatopancreatobiliary 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song Cheol","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Ulsan University College of Medicine and Asan Medical Center, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Morine","sequence":"additional","affiliation":[{"name":"Department of Surgery, Tokushima University, Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuo","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Surgery, Tokushima University, Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali 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