With the maturity of surgical technology, the follow-up of surgical equipment, and the update of surgical concepts, PD has not only been exclusive to large central hospitals. CR-POPF is the focus of attention after PD surgery, and many related studies have been carried out to influence CR-POPF. At present, the pancreas itself is generally considered to be a powerful factor in predicting CR-POPF [3]. However, due to strong subjective judgment, perioperative laboratory indicators have been studied more, among which the CRP prediction of CR-POPF has been confirmed by many studies [5, 8, 9]. The monitoring of perioperative CRP undoubtedly increases the economic burden on patients. Therefore, we need to find an economical and convenient indicator that can predict CR-POPF.
In recent years, high TBIL has been thought to increase the risk of postoperative complications, and preoperative biliary drainage can improve postoperative outcomes [13, 14]. However, regarding TBIL, the relationship between preoperative biliary decompression, perioperative complication rate, and mortality has been a hot topic of controversy [15–17].
A meta-analysis revealed that preoperative biliary drainage in patients with obstructive jaundice did not yield substantial advantages during surgery. Furthermore, the procedure of preoperative biliary drainage was found to increase the occurrence of complications after surgery [18]. Based on a multicenter randomized controlled trial, it was found that patients with obstructive jaundice who received preoperative biliary drainage did not experience any significant advantages during surgery. Additionally, performing early direct surgery did not result in a higher occurrence of postoperative complications compared to surgery after preoperative biliary drainage [19]. The Lancet recently published a prospective research examining the prognostic impact of preoperative biliary drainage on patients suffering from obstructive jaundice. The results revealed that the occurrence of postoperative complications and mortality rates were comparable between the group of patients who underwent preoperative biliary drainage as well as the group who did not. The postoperative management procedures of patients were recognized as a possible variable influencing postoperative complications [20]. A retrospective study found that the serum TBIL level of PD patients before surgery was higher than 250 µmol/L. Postoperative bleeding and CR-POPF were less likely to happen if biliary drainage was done before surgery [21]. A retrospective study conducted recently revealed that preoperative biliary drainage could lower the overall postoperative complication rate in patients with proximal obstructive jaundice and that perioperative TBIL was an independent risk factor for postoperative problems. Since the surgical methods involved in this study were not limited to pancreatic surgeries, the pancreatic fistula was not meaningful in the study [22]. At present, there are many studies on preoperative biliary drainage and CR-POPF, most of which are limited to the operation, and there is no unified conclusion. Therefore, we changed the research direction to explore the effect of postoperative TBIL on CR-POPF.
Hyperbilirubinemia can lead to severe internal environmental disorders and multiple complications, including impaired immune response, nutrient malabsorption, biliary tract infection, liver dysfunction, coagulation dysfunction, and even death. Studies on the prognostic effects of high TBIL have been reported [23–25]. In a retrospective study up to 9 years after PD surgery, it was found that postoperative increases in TBIL were associated with poor survival prognosis in patients [26].
In clinical work, we found that during the perioperative period of PD patients, the postoperative TBIL level was mostly decreased compared with those before surgery, but the reduction effect was different, even though the preoperative biliary drainage. Together with the aforementioned research, we think that TBIL may have a significant impact on PD patients' postoperative complication rate and prognosis. Preoperative TBIL is not accurate enough to predict the occurrence of CR-POPF, and the prediction of preoperative biliary drainage on CR-POPF is highly controversial, which further confirms our idea of using postoperative TBIL to predict CR-POPF.
Our study is the first to report the prognostic value of postoperative TBIL on CR-POPF after PD surgery. The CR-POPF group's hospital stay was longer than the non-CR-POPF group's. Higher preoperative CRP, higher postoperative TBIL, and softer pancreas texture were risk factors for CR-POPF, and the predictive value of postoperative TBIL was the highest.
To further improve the study, the postoperative day 3 TBIL level was changed from measurement data to counting data by cut-off value (89.45 mol/L). Among the categorical variables, our study results showed that intraoperative blood loss, residual pancreatic texture, pancreatic duct diameter, and postoperative TBIL may be related factors affecting CR-POPF after PD surgery. In multivariate logistic regression, postoperative TBIL and residual pancreatic texture were independent risk factors for CR-POPF. Our results are similar to those of Shen Z. et al. That TBIL is the independent risk factor of CR-POPF [21].
Kowal et al. pointed out that a rise in TBIL after surgery may not only show a higher chance of an early biliary fistula but also cause cholestasis after surgery, which can cause infections aggravatingly and worsen patients' prognosis [27]. Studies have shown that postoperatively elevated serum TBIL may help predict the development of severe POPF. In addition, factors such as the status of the liver and pancreas, the degree of inflammation, and fibrosis are also closely related to the occurrence of severe POPF [28]. To some extent, TBIL reveals the synthesis and metabolism of liver function. Elevated serum TBIL concentrations may indicate obstruction of the biliary tract. When bilirubin excretion is blocked, it may lead to liver insufficiency, nutrient metabolism disorders, an increase in bile duct pressure, and abnormal platelet production [29]. In addition, animal experiments have shown that biliary obstruction may also lead to increased levels of serum inflammatory cytokines and endotoxins, intestinal flora disorders, and intestinal mucosal barrier damage [30]. We believe that a high level of postoperative TBIL may lead to increased levels of inflammatory cytokines and endotoxins, which may cause bacterial translocation, aggravate the stress state of patients, affect the healing of surgical anastomosis, and thus increase the risk of CR-POPF.
It is important to note a few of this study's shortcomings. First, there is no accurate index for the determination of intraoperative pancreatic texture, which is subjective. Besides, to validate our findings, it is necessary to conduct high-quality multi-center randomized controlled trials (RCTs) due to the limitations of this study, such as its retrospective nature and small sample size.
Ultimately, we believe that measuring TBIL level on the third day after surgery can be a convenient, cost-effective, and reliable method for predicting CR-POPD after PD. In summary, after undergoing PD surgery, it was observed that the level of CRP before the operation, the residual pancreatic texture, and the Postoperative day 3 TBIL level were all independent factors that might predict the occurrence of CR-POPF. Postoperative day 3 TBIL level are the most reliable indicator for predicting CR-POPF after PD surgery.