Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with poor survival. Recent reports suggest that tissue hypercapnia (elevated levels of CO2) promotes an aggressive PDAC phenotype and resistance to therapy. End-tidal carbon dioxide (ETCO2) measurement offers a composite measure of ventilation, systemic perfusion, and tissue CO2 production. We hypothesized that ETCO2 levels in patients with PDAC undergoing curative-intent pancreaticoduodenectomy could serve as a prognostic marker: (1) low levels indicating decreased circulatory reserves, and (2) high levels indicating increased tissue hypercapnia-both of which may result in worse oncologic outcomes.
Study design: This was a single, high-volume, institutional, retrospective cohort study of patients who underwent pancreaticoduodenectomy for PDAC (2017 to 2023). Intraoperative ETCO2 data were obtained from anesthesia records. Mean ETCO2 was calculated for each patient. ETCO2 groups were stratified by quartiles (Q1 to Q4): low (Q1), normal (Q2 to Q3), and high (Q4). The primary endpoints were disease-free survival and overall survival (OS).
Results: The final cohort included 243 patients (49% men, median age 68.5 years [interquartile range 61.3 to 74.9]). Both low and high ETCO2 were associated with poorer OS compared with normocapnia (p < 0.05 for both). Cox regression analysis identified both low and high ETCO2 as independent and significant factors for disease-free survival (hazard ratio 1.80 and 1.65, respectively) and identified high ETCO2 as a risk factor for OS (hazard ratio 1.65) compared with normocapnia.
Conclusions: Mean intraoperative ETCO2 is a strong marker of oncologic outcomes in patients with PDAC after pancreaticoduodenectomy, with both extremes of the spectrum linked to a worse disease course. This observation has implications for patient selection and decision-making in cancer care.
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