A commentary on: “Effect of Preoperative Autologous Blood Storage in Major Hepatectomy for Perihilar Malignancy: A Randomized Controlled Trial”

Post-hepatectomy liver failure (PHLF) remains a significant surgical complication for patients undergoing major liver resection for cholangiocarcinoma. Not only is this a recognised cause of perioperative mortality in major hepatectomy, there is also emerging evidence to suggest PHLF is associated with worse longer term oncological outcomes including median overall survival (1). A combination of liver reserve volume, extent of resection, physiological reserve, and perhaps receipt of allogenic blood, all provide a multitude of interacting factors influencing the presence of PHLF. The International Study Group of Liver Surgery (ISGLS) have developed a grading system to stratify the severity of PHLF (2). Grade A PHLF requires no change of the patient’s clinical management. The clinical management of patients with grade B PHLF deviates from the regular course but does not require invasive therapy. The need for invasive treatment defines grade C PHLF. Its incidence varies widely based on reporting strategy, with rates between 20–50% published across the literature for a combination of grade B and C PHLF (3). A strategy to mitigate this, pre-operative storage of autologous blood, attempts to reduce the incidence of PHLF, however the evidence on this is limited to small, retrospective cohort studies (4,5). Furthermore, the underlying physiological basis for such a hypothesis is not clear. Perhaps through the optimisation of perioperative anaemia and minimising hepatic ischaemia, preoperative stored autologous blood may reduce the risk of PHLF. The authors present a single-centre, randomised trial comparing receipt of allogenic blood alone (control) versus pre-stored, autologous blood in addition to allogenic blood when required (6). The authors concluded there was no difference between the arms of the trial, and extended this further to report a change in their local practice in discontinuing routine pre-operative autologous blood storage.

Allogenic blood products have been associated with worse oncological outcomes for patients undergoing surgery for malignant disease, a phenomenon attributed to transfusion-related immunomodulation reproducible over decades of work across surgical oncology sub-specialties (7-9). Autologous blood storage has also been employed to mitigate other risks associated with allogenic transfusion, including immunosuppression, infectious complications, and transfusion-related reactions (10,11). However, the advent of enhanced surgical techniques, perioperative care protocols, deployment of the Pringle manoeuvre, low intraoperative central venous pressure (<4 mmHg), and safer blood transfusion practice, has called into question the necessity of this approach in tackling blood loss (12,13). In their study, Onoe et al. randomised 113 patients undergoing major hepatectomy with bile duct resection for perihilar malignancy to receive either pre-stored (autologous) or allogeneic blood transfusion. The trial’s primary outcome—PHLF—was evaluated according to internationally recognised criteria. Secondary outcomes included Clavien-Dindo Grade III or higher complications, hospital stay duration, and overall morbidity. The authors found no statistically significant difference in PHLF rates (17% vs. 19%, P=0.76) or other relevant perioperative outcomes between the two groups, including 90-day mortality (0% vs. 4%, P=0.22). This finding refutes the hypothesis that autologous blood storage confers a clinical benefit in this surgical population.

This trial was designed in a robust manner to answer a specific question, with randomisation of participants, and inclusion of a well-defined cohort undergoing a uniform surgical procedure. Patients were randomised on a 1:1 basis, and Allocation was achieved using a minimization method balancing age, sex, plasma indocyanine green clearance rate (ICG-K), type of hepatectomy, and clinical nodal metastasis. Allocation concealment was not possible due to the nature of the intervention proposed. By focusing on major hepatectomy—a relatively standardised and limited set of operations—the study aimed to eliminate heterogeneity observed in prior analyses assessing pre-operative blood storage, thus enhancing its internal validity. The study’s primary endpoint (PHLF) is both clinically relevant and directly linked to patient outcomes. The findings challenge the routine use of autologous blood storage, a practice that incurs significant costs and logistical demands. Given the comparable outcomes between groups, the study supports discontinuing this practice, thereby potentially freeing up a valuable resource without compromising patient safety. Since the 1990s, pre-operative allogenic blood storage has been long investigated for its potential utility and cost-efficacy in the elective perioperative setting, however limited health benefit, considerable cost (between $235,000–$23,000,000 per quality adjusted life year gained), and improved allogenic transfusion practices have all called into question the role of pre-operative autologous blood storage (14).

Despite its strengths, the trial has limitations that warrant discussion. First, the exclusion of patients with cirrhosis or compromised liver function limits the generalisability of findings to these high-risk subgroups. In a large multi-centre international cohort study, liver cirrhosis was identified as an independent risk factor for the development of PHLF, severe complications, and mortality in patients undergoing hepatectomy (15). Additionally, the trial was conducted at a single expert centre, where surgical outcomes may not reflect those achievable in less experienced settings. While the study is limited to a single centre, the expertise of this particular department in this practice should not be overlooked, and perhaps failure to derive benefit from this technique by this group would reflect any attempts to seek benefits from stored blood elsewhere. Moreover, while the trial focuses on short-term outcomes, its findings do not address potential long-term benefits, such as reduced tumour recurrence associated with avoiding allogeneic transfusion-induced immunosuppression (8).

Advances in surgical technique have substantially reduced intraoperative blood loss, diminishing the need for transfusion strategies. For example, meticulous dissection techniques with cavitron ultrasonic aspirator (CUSA), enhanced visualisation, and intraoperative haemostasis methods have been pivotal in lowering blood loss from historical averages of >4,000 to <1,000 mL in expert centres (16-18). The median blood loss reported in this study (846 mL) reflects these advancements, underscoring the diminishing relevance of preoperative blood storage. However, an important consideration not discussed is the role of intraoperative cell salvage and autologous transfusion. This has been shown to improve perioperative outcomes in various surgical settings (19-21), however specifically for oncological liver surgery, the evidence is limited to a single-centre retrospective cohort study (22). One important theoretical consideration is the blood-loss tolerance of individual patients, which may provide a window into the relative benefit patients may derive from receipt of autologous blood (23).

In summary, the authors present the results of a trial showing a lack of benefit from pre-operative autologous stored blood in preventing PHLF. Further questions remain, including the longer-term oncological impact of potential avoidance of allogenic transfusion, as well as the health resource implications of decommissioning this strategy while maintaining patient safety. Future work in this area should consider the impact of intraoperative cell salvage, individual patient factors such as blood-loss tolerance, and broadening the inclusion of a more diverse range of patients to extend the generalisability of the results of a future study.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, AME Surgery Journal. The article has undergone external peer review.

Peer Review File: Available at https://asj.amegroups.com/article/view/10.21037/asj-24-54/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://asj.amegroups.com/article/view/10.21037/asj-24-54/coif). The authors have no conflicts of interest to declare.

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