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.

Background: Patients with type 1 diabetes complicated by severe hypoglycemia and impaired awareness remain at high risk of mortality despite advances in diabetes treatment. Pancreas transplantation offers definitive β-cell replacement; however, contemporary real-world data on hypoglycemia outcomes are limited. Methods: We performed a retrospective single-center cohort study of adult patients undergoing pancreas transplantation at The Mount Sinai Hospital between 1 January 2010 and 31 December 2024. Transplant types included simultaneous pancreas–kidney (SPK), pancreas after kidney (PAK), and pancreas transplant alone (PTA). The primary outcome was the incidence of severe hypoglycemia following transplantation, with secondary outcomes including graft survival, patient survival, biopsy-proven rejection, and infectious complications. Post-transplant HbA1c and continuous glucose monitoring data were not systematically captured and could not be analyzed. Results: A total of 100 pancreas transplants were performed (SPK 73%, PAK 26%, PTA 1%), over a median follow-up of 8.5 years (IQR 4.5–13.7). Pretransplant hypoglycemia or hypoglycemia unawareness was present in 63% of recipients. Documented impaired awareness specifically was recorded in a smaller subset (9%). No episodes of severe hypoglycemia occurred following transplantation, and hypoglycemia unawareness resolved in all patients with available follow-up. Two patients (2%) had a hypoglycemic episode recorded post-transplant; in one, the episode occurred after graft failure while on insulin, and neither was a severe (third-party-assisted) event in a functioning graft. Death-censored graft survival was 94.0% at 1 year, 91.6% at 3 years, 83.0% at 5 years, and 80.5% at 10 years, while patient survival was 95.0%, 89.5%, 88.2%, and 84.2% at the same time points. Rejection occurred in 21%, and infectious complications in 31% of recipients. Conclusions: Pancreas transplantation provided complete and durable protection from clinically documented severe hypoglycemia, with excellent long-term graft and patient survival. In the absence of systematic post-transplant HbA1c and continuous glucose monitoring data, these findings should be read as freedom from clinically recognized severe hypoglycemic events rather than as documented normoglycemia, supporting its role as the most definitive β-cell replacement strategy in appropriately selected patients.