When and how can in-hospital deaths following pancreaticoduodenectomy be prevented?

The mortality rate following pancreaticoduodenectomy (PD) reached 25–30% in the 1970s–1980s, but has significantly decreased to <2–5% thereafter (1-7). Owing to advances in surgical and anesthetic techniques, the concentration of medical care at high-volume medical institutions, the introduction of standardized recovery processes, and improved understanding and management of common complications, such as postoperative pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE), and postpancreatectomy acute pancreatitis (PPAP), as classified by the International Study Group for Pancreatic Surgery (ISGPS) (8-11)—all of these factors combined have led to a dramatic decline in postoperative mortality rates (12,13). However, reported mortality rates vary widely and remain high among cohorts. A nationwide study in Germany reported a 10.1% in-hospital mortality after PD (14). The “Windows of opportunity to prevent failure to rescue after PD” scrutinizes in-hospital mortality after PD at Heidelberg University Hospital from 2003 to 2021 (15). Kinny-Köster et al.’s study involved in-patients who died after elective PD (n=4,474) to identify time-dependent vulnerabilities and potential intervention windows for improving rescue from life-threatening postoperative complications. Mortality clusters were classified into three root-cause categories based on the pathophysiology: post-pancreatectomy-specific complications (PP; 51.9%), visceral vasculature-related events (VV; 25.6%), and cardiopulmonary complications (CC; 17.9%). Notably, Kinny-Köster et al.’s study identified time-dependent risk patterns and windows of opportunity for rescuing patients from complications. The median interval between root cause onset and death significantly differed among clusters; approximately 23 days (PP), 11 days (VV), and 1 day (CC), highlighting distinct “windows” for intervention depending on the underlying pathology. The findings align with those of Giuliani et al., supporting the general concept of time-dependent vulnerabilities after PD. Mortality after PD occurs via three distinct pathways: pancreas-specific complications (pattern A, 71.4%; median, 43 days), early deterioration linked to surgical complexity (pattern B, 15.9%; median, 18 days), and unknown causes after uneventful course (pattern C, 12.7%; median, 8 days). This knowledge can facilitate the identification of the best targets for improvement (16). The PORSCH trial, a nationwide, stepped-wedge randomized controlled trial in the Netherlands, evaluated a multimodal, daily algorithm for early recognition and minimally invasive management of postoperative complications after pancreatic resection (17). Compared to standard care, algorithm-based care was associated with an approximately 50% reduction in the primary composite outcome (bleeding requiring invasive intervention, organ failure, or 90-day mortality) (adjusted relative risk, 0.48). The 90-day mortality rate has decreased from 5% to 3%. Although computed tomography, antibiotic administration, and radiological drainage were performed earlier, the total costs were comparable with those of standard care. The PORSCH trial demonstrates the concept of a “windows of opportunity” as a practical care pathway and contributes to improving the timing of interventions for the PP, VV, and CC clusters. Additionally, standardization of the definition and severity of POPF or PPAP can enable consistent risk stratification and timely intervention for PP-related conditions (8,11). Mihaljevic et al. proposed a foundational framework to stratify PD procedures into four types according to their complexity; standard PD, PD with the portomesenteric vein resection, PD with multivisceral resection, and PD with arterial resection (18). The 90-day mortality increased with type (2.9%, 4.2%, 6.3%, and 10.3%), indicating the need for risk-aware monitoring and rescue planning. In cases involving combined resection and reconstruction of the portal vein or/and arteries, thrombosis risk, prevention, and treatment are closely linked to the timing of intervention on VV cluster (19-22). Although prehabilitation before oncologic pancreatic resection is promising, evidence remains limited and heterogeneous (23). To reduce postoperative complications and promote recovery, optimizing physical conditioning and nutritional status are associated with mitigating rapid CC-type deterioration (23). Using information from the national Medicare claims database and Nationwide Inpatient Sample in the United States, the absolute differences in adjusted mortality rates for pancreatic resection between very low- and high-volume hospitals were 16.3% and 3.8%, respectively (24). In the absence of reliable information on the quality of surgical care, patients undergoing pancreatic resection can significantly improve their survival rates by choosing a hospital in an area that performs a high number of surgeries. However, some researchers have emphasized that in certain cases, alternative strategies (total pancreatectomy for high-risk anastomoses) may be appropriate and suggested that the rescue window following PD must be interpreted concerning biological and alternative surgical options for the tumor (25,26). Tube pancreatostomy for complete external drainage of pancreatic juice following pancreatoduodenectomy and a subsequent second-stage pancreatojejunostomy can avoid the fatal outcomes associated with pancreatojejunal anastomotic leakage following pancreatoduodenectomy in emergency and high-risk cases (27,28). Over the past 20 years, minimally invasive surgery has advanced significantly, suggesting that differences in short-term outcomes based on surgical approach may influence mortality rates and opportunities for life-saving interventions. This provides a perspective that the interpretation of the “window of opportunity” for life-saving interventions depends on the choice of surgical intervention (29-31). Thus, clinicians should be aware of the distinct time horizons for failure-to-rescue, depending on the root cause. To prevent PP complications, clinicians should continue to provide meticulous care and consider alternative options, such as total pancreatectomy or two-stage surgery, in high-risk cases. The implementation of strict monitoring and rapid response protocols focused on the early phase immediately following PD initiation to address VV and CC events. For medical institutions, centralization to high-volume centers, using standardized PD protocols and strong postoperative care pathways may yield better outcomes and clearer rescue windows. The validity of the three-cluster framework should be verified across diverse healthcare settings, and the scope of the analysis should be expanded to include 90-day mortality and long-term outcomes. Furthermore, to optimize life-saving interventions in clinical practice, the integration of prehabilitation and algorithm-based care must be explored.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Gland Surgery. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0318/coif). The authors have no conflicts of interest to declare.

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