Optimizing Risk Stratification in Elderly Patients With Perihilar Cholangiocarcinoma: Bridging Objective Indices and Holistic Assessment

We appreciate the opportunity to respond to the insightful comments by Dr. Koker regarding our article, “High preoperative Glasgow prognostic score increases a risk of hospital mortality in elderly patients with perihilar cholangiocarcinoma”. We thank Dr. Koker for their thoughtful analysis and for enhancing the importance of multidimensional frailty assessment in elderly patients undergoing hepatobiliary surgery. Dr. Koker raises several pertinent points that warrant further discussion. First, we agree that while the GPS is a robust indicator of systemic inflammation and nutritional status, it does not encompass all dimensions of frailty. As noted in the Letter, incorporating standardized metrics such as the Clinical Frailty Scale, G8, or sarcopenia indices like the psoas muscle area would indeed provide a more holistic preoperative profile. In our clinical practice, we increasingly recognize that biological age and functional reserve are often more critical than chronological age. However, the strength of the GPS lies in its objectivity and widespread availability, requiring only routine blood samples (CRP and albumin). Second, regarding the concern about single-point measurements in the context of biliary obstruction or cholangitis, we must clarify our preoperative protocol. In our study, all surgeries were performed only after achieving a stabilized state, with a serum bilirubin level of less than 2 mg/dL. Furthermore, blood samples for the GPS were obtained a few days before surgery, specifically when there was no clinical evidence of active infection or inflammatory conditions. While we agree that dynamic “delta-GPS” or trajectory-based scores could offer more granular predictive power, our findings suggest that even a static preoperative GPS, when measured in a stabilized state, remains a critical surrogate marker for hospital mortality in elderly patients. Third, Dr. Koker correctly points out that our study did not specify preoperative nutritional or anti-inflammatory interventions. Given the retrospective nature of our study spanning two decades (2000–2020), standardized prehabilitation protocols were not uniformly implemented across the entire cohort. We fully concur that exploring whether a high GPS can be “reversed” through intensive prehabilitation is an essential direction for future prospective research. Finally, while GPS has been reported as an independent prognostic factor across various age groups [1, 2], our investigation specifically targeted the elderly cohort to identify unique risks. We acknowledge that the small sample size after propensity score matching (n = 61 per group) limits the statistical power for multivariate analysis. Crucially, we did not perform an extensive analysis of the younger cohort regarding inflammatory reserve or recovery capacity. Therefore, the question of how the relationship between age and systemic inflammation affects the ability to recover from complications should be addressed in future comprehensive studies. In conclusion, we believe our study provides a valuable “starting point” for using the GPS as a practical screening tool for frailty in elderly surgical candidates. We welcome the integration of longitudinal inflammatory profiling and multidimensional assessment tools, as suggested by Dr. Koker, to further refine our surgical decision-making and improve outcomes in this vulnerable population. This article is linked to Kokumai et al. papers. To view this article, visit https://doi.org/10.1002/jhbp.70078. The data that support the findings of this study are available from the corresponding author upon reasonable request.