The effect of perioperative blood transfusion (PBT) on the prognosis of ampullary carcinoma (AC) is still debated.

To explore the impact of PBT on short-term safety and long-term survival in AC patients who underwent pancreaticoduodenectomy.

A total of 257 patients with AC who underwent pancreaticoduodenectomy between 1998 and 2020 in the Cancer Hospital, Chinese Academy of Medical Sciences, were retrospectively analyzed. We used Cox proportional hazard regression to identify prognostic factors of overall survival (OS) and recurrence-free survival (RFS) and the Kaplan-Meier method to analyze survival information.

A total of 144 (56%) of 257 patients received PBT. The PBT group and nonperioperative blood transfusion group showed no significant differences in demographics. Patients who received transfusion had a comparable incidence of postoperative complications with patients who did not. Univariable and multivariable Cox proportional hazard regression analyses indicated that transfusion was not an independent predictor of OS or RFS. We performed Kaplan-Meier analysis according to subgroups of T stage, and subgroup analysis indicated that PBT might be associated with worse OS (P < 0.05) but not RFS in AC of stage T1.

We found that PBT might be associated with decreased OS in early AC, but more validation is needed. The reasonable use of transfusion might be helpful to improve OS.

Ampullary carcinoma (AC) is a rare malignancy originating from the ampulla of Vater. The incidence of ACs has increased over the past several decades and accounts for 16% of all periampullary cancers[1,2]. Pancreaticoduodenectomy (PD) is currently the primary treatment choice for AC, and the resection rates have been reported to be more than 90% in a Japanese report[3]. Although the postoperative mortality of PD has decreased in recent decades[4], the postoperative morbidity rate remains high at 30% to 55%[5-7]. Moreover, many patients require perioperative blood transfusion (PBT) during PD due to the sophisticated surgical procedure[8,9].

A randomized trial has shown that allogeneic blood transfusions can increase the risk of colorectal cancer recurrence[10]. However, the safety and prognostic effect of PBT on patients undergoing PD remains controversial. Several studies[11,12] suggested that PBT was related to increasing rates of postoperative complications, and a previous study[13] showed that PBT was an independent risk factor for serious infections following PD. For long-term oncological outcomes, PBT in patients was associated with decreased overall survival (OS) after PD in several observational studies[14-17], but other studies[18,19] did not show this association in multivariable analysis.

With respect to AC, the subgroup analysis conducted by Park et al[20] showed that PBT was an independent risk factor for poor prognosis in AC patients (P = 0.029). However, another retrospective study did not find any adverse effect of PBT on survival in AC patients[21]. To clarify the connection between PBT and both long-term survival and short-term safety following PD of AC, we performed a retrospective analysis.

The adverse effect of PBT on the prognosis of digestive system tumors is still controversial. In this study, there was no discernible difference in short-term complications and long-term survival outcomes between PBT and no PBT patients with AC who underwent PD, whereas we found that PBT might reduce the OS in early pathologic stage AC patients. Our study suggested that more reasonable transfusion may be helpful in improving OS in early AC.

In this study, transfusion was not significantly associated with increased risks of OS and RFS. The aforementioned study also did not find any adverse effect of PBT on survival in 501 AC patients[21]. Similarly, a recent study indicated that transfusion was not a significant adverse prognostic factor in 404 AC patients after PD[18]. However, another retrospective study showed that PBT seemed to have an adverse impact on the survival of patients who underwent PD[20], which included 130 AC patients, 58% of whom underwent intraoperative transfusion. Consensus conclusions have also been reached in periampullary cancer in Korea[15]. Such conflicting results might be related to several factors. First, early-stage patients accounted for only a small part in our study, while in Park’s study[20], early-stage patients accounted for a considerable proportion (40% vs 15%). Although we found that transfusion was correlated with worse prognosis in early-stage patients, this was not enough to affect the entire study. Second, decisions on transfusion were mainly made by surgeons and anesthetists during the perioperative period, and transfusion criteria usually varied in different medical organizations, which might impact the results. Third, the inadequate sample size due to the lower prevalence of AC might also be a possible reason. An analysis containing a larger sample size is needed in the future. Fourth, the presence of unknown confounding factors might influence our study in some ways.

Subgroup analysis indicated that the impact of PBT on prognosis was more pronounced in patients with lower stages. We found that the no PBT group was associated with better OS but not RFS in the T1 stage. Similar results were also reported by Cata[22] for 636 non-small cell lung cancer patients. Moreover, Wang and colleagues[23] observed that transfused patients had significantly greater rates of disease recurrence in stage I non–small cell lung cancer. Our research also showed some discrepancies in RFS with T1 stage patients but did not reach statistical significance. There were two potential reasons to explain the adverse effect of transfusion. First, previous studies suggested that transfusion of allogenic blood induced immunosuppression and lowered the activity of natural killer cells and/or helper T cells[10,24,25]. Goubran et al[26] propounded that transfusion might stimulate tumor growth through an increase in the mitogenic activity of platelet-derived growth factors. Therefore, the immunosuppressive effect of transfusion might have an adverse impact on patient survival. Another possible reason was that the higher stage AC was more aggressive, which was related to shorter survival. On the other hand, AC patients with early-stage disease had better survival outcomes. Thus, the adverse prognostic influence of transfusion could be seen[15].

This study indicated that transfusion would not increase the risk of short-term complications after PD. Likewise, Sutton et al[17] reported that PBT was not related to an increase in infectious complications. In contrast, several previous studies[13,27,28] showed that PBT among patients with PD was associated with increased rates of various postoperative complications. Ball et al[27] demonstrated that the overall morbidity rate after PD was 37%, and 30-d morbidity increased in a stepwise manner with the number of RBC transfusions. Zhang et al[13] observed that there was a significant association between PBT and serious infections after PD. There were several reasons to explain the increase in complications. First, acute hemorrhage could induce ischemia and hypoxia of tissues, which might even increase pancreatic fistula. Transfusions could be essential to avoid inducing short-term postoperative complications by improving oxygen supply and minimizing hypoxic damage to organs[28]. Second, anemia with concomitant poor nutritional status might also be an adverse factor for postoperative recovery. Third, transfusion-related immunosuppression was thought to be a reason for the increasing risk of infections after blood transfusion[29].

To the best of our knowledge, this study analyzed the impact of the largest number of transfusions in AC patients after PD, both short-term complications and long-term survival were evaluated simultaneously. Then, we implemented further subgroup analysis of the dose-response and T stage. Limitations of this study should be observed. First, this research was a single-center retrospective study with potential selection bias and other confounding factors associated with PBT that may impact OS and RFS. Second, preoperative hemoglobin level, intraoperative blood loss, and transfusion time (pre, intra, and post) were missing, which might have influenced this research. In addition, the granular data of systemic chemotherapy were also missing. Third, some subgroups contained a relatively small number of patients, which might affect the accuracy of our results. Finally, decisions on transfusion were usually made by surgeons or anesthesiologists individually, which may have impacted outcomes. This study nevertheless supports some potential clues for transfusion.

According to our study, PBT was not an independent prognostic factor for AC patients after curative PD. PBT might be associated with decreased OS in early AC. Avoiding PBT whenever possible might be helpful to improve OS. More multicenter and prospective validations are needed.