{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:46:59Z","timestamp":1791586019250,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Despite advances in surgical technique and perioperative care, pancreatic ductal adenocarcinoma (PDAC) remains associated with poor survival. Sarcopenia is highly prevalent in PDAC and is consistently associated with inferior survival and reduced tolerance of systemic therapy. However, interventions primarily aimed at increasing muscle mass through nutritional supplementation and resistance-based exercise have yielded limited improvements in clinically meaningful postoperative outcomes. This has prompted increasing interest in sarcopenia as a marker of broader biological vulnerability rather than isolated physical deconditioning. Emerging clinical, translational, and experimental evidence demonstrates that skeletal muscle and adipose tissue function as active immunometabolic organs, and that cancer-associated inflammatory pathways drive early muscle loss, immune dysfunction, and impaired physiological recovery. Across multiple clinical cohorts, sarcopenia is reproducibly associated with worse overall survival and failure to complete adjuvant therapy, but not consistently with increased postoperative complications, suggesting that its prognostic relevance lies in impaired recovery and oncological fitness rather than immediate surgical risk. Translational studies further indicate that sarcopenia identifies patients with reduced antitumor immune competence, particularly in early-stage disease. This review synthesizes current evidence linking sarcopenia, immune dysfunction, and surgical outcomes in PDAC and examines implications for perioperative care. We propose that immunometabolic-informed prehabilitation, integrated with existing nutritional and exercise strategies, may represent a more effective approach to improving recovery, treatment tolerance, and durable oncological outcomes following PDAC resection.<\/jats:p>","DOI":"10.3390\/cancers18081205","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:55:12Z","timestamp":1775807712000},"page":"1205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sarcopenia as a Marker of Immunometabolic Vulnerability in Pancreatic Ductal Adenocarcinoma"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4600-5624","authenticated-orcid":false,"given":"Mukund","family":"Karthik","sequence":"first","affiliation":[{"name":"Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia"},{"name":"Research, Innovation & Surgical Education (RISE), Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Shahrestani","sequence":"additional","affiliation":[{"name":"Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia"},{"name":"Recanati\/Miller Transplantation Institute, Mount Sinai Hospital, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-soo","family":"Park","sequence":"additional","affiliation":[{"name":"Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia"},{"name":"Department of Upper GI Surgery, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8857-0779","authenticated-orcid":false,"given":"Christian","family":"Ratnayake","sequence":"additional","affiliation":[{"name":"Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia"},{"name":"Research, Innovation & Surgical Education (RISE), Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charbel","family":"Sandroussi","sequence":"additional","affiliation":[{"name":"Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia"},{"name":"Research, Innovation & Surgical Education (RISE), Sydney, NSW 2050, Australia"},{"name":"Department of Upper GI Surgery, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia"},{"name":"Department of Upper GI Surgery, Chris O\u2019Brien Lifehouse, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6126","DOI":"10.1097\/JS9.0000000000000989","article-title":"Preoperative Low Skeletal Muscle Mass Index Assessed Using L3-CT as a Prognostic Marker of Clinical Outcomes in Pancreatic Cancer Patients Undergoing Surgery: A Systematic Review and Meta-Analysis","volume":"110","author":"Raoul","year":"2023","journal-title":"Int. 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