While the incidence of serious hemorrhagic complications and postoperative liver failure decreased significantly in the past 3 decades, the bile leakage rate has been quite stable and has become, at the present time, the leading specific surgical complication after liver resection. The incidence of bile leakage has not changed over the past few years, ranging from 6.7 to 18.6% [2,3,4,5]. In most cases, the bile leakage does not threaten the lives of patients. On the other hand, in some cases, the bile leakage causes the development of septic complications that increase the risk of postoperative death. According to Li S. et al., bile leakage significantly increases the length of postoperative hospital stay compared to the patients without biliary complications (52 ± 25 and 28 ± 10 days, respectively, p < 0.001) [16]. In addition to the prolongation of hospital stay and reconvalescence period, the bile leakage drives the need for repeated surgery or interventional procedures.

Studies that determine the bile leakage risk factors remain sparse and controversial. It has been noted that biliary complications appear more often after hepatic resection in case of malignancy than after hepatic resection in case of benign disease (19.5% and 4.8%, respectively, p < 0.05) [17]. Some types of resections have an increased risk of bile leakage. For instance, mesohepatectomy, bisegmentectomy 5 and 8, segmentectomy 1, and segmentectomy 4 are associated with the increased risk of devascularization and damage of large bile ducts [18, 19]. Operative time, intraoperative blood loss of more than 1.5 l, and the presence of acute purulent inflammation in the preoperative period are also considered as predictors of the bile leakage development [19, 20].

The bile leakage prevention was actively considered even in the 1980 s. Kubo S. et al. were the first to suggest using cholangiography before liver resection to reduce the incidence of postoperative biliary complications [21]. Follow-up studies were aimed at finding an optimal method for intraoperative diagnosis of bile leakage. Several trials have been devoted to bile leakage tests with saline solution. Ijichi M. et al. were among the pioneers in this research field. However, they showed no significant difference in the frequency of bile leakage between the study and control groups (6% and 4%, p = 0.95) [22]. Interestingly, Kayaalp C. et al. significantly decreased the rate of bile leakages owing to the test with saline solution (8.8% and 27.7%, respectively, p = 0.03). The postoperative hospital stay of the patients who received this procedure was also reduced [23].

Lam C. et al. used methylene blue for leakage testing. There was a decrease in the incidence of postoperative bile leakage in the study group compared with the control group (3.6% and 7.4%, respectively, p < 0.05) [24]. Zimmitti G. et al. suggested using the gas test to diagnose the bile leakage. The essence of the method was to introduce gas into the lumen of the biliary tree and visualize it using ultrasound. When the gas bubbles accumulated in the ducts, the bile ducts were supposed to be leakproof. According to the study, using the test significantly improved the intraoperative detection of bile leakage, and the incidence of postoperative biliary complications was significantly higher in the control group (62.1% and 8.3%, p < 0.001) [25].

Another method is used for the bile leakage intraoperative diagnosis, which consists of indocyanine green (ICG) introduction into the common bile duct. The disadvantage of this approach is its complexity due to the use of an infrared camera. This test increases the probability of the bile leakage intraoperative detection compared to the saline solution [26]. The study of Kaibori M. et al. reported a reduction of postoperative bile leakage rates after liver resection from 10 to 0% due to intraoperative verification of bile leakages assisted by ICG [27]. Another study conducted by Hanaki T. et al. has similarly reported a reduction of postoperative bile leakage rate from 7.7 to 0% [28]. Both studies were retrospective comparative studies. Surprisingly, the recent systematic review and meta-analysis of ICG application for liver resection for liver malignancies has not found advantages of intraoperative ICG in the prevention of postoperative bile leakages, reporting similar rates of postoperative bile leakages in both groups, 3.1% in ICG group and 3% in non-ICG group [29]. These data are in significant contrast with outcomes reported by Kaibori et al. and Hanaki et al. [27, 28]. Although ICG in liver surgery has spread tremendously and has shown evidence to be effective in improving the rate of R0 liver resection [29], its role in the prevention of postoperative bile leakages should be verified in prospective trials [30].

In this study, we tested the effectiveness of the White Test (the fat emulsion injection through the cystic duct) for the prevention of postoperative biliary complications, proposed by Nadalin S. et al. [6]. Initially, the White Test intraoperative application demonstrated a significant reduction in postoperative bile leakage cases compared to the control group (5% and 22%, p < 0.05) [6]. The recent research works results are ambiguous. Only one randomized trial (n = 107) regarding the White Test effectiveness evaluation was described in the literature when this work was initiated. In this work, Liu Z. et al. also showed a difference in the frequency of biliary complications between the group with the White Test and the control group (3.7% and 14.8%, p < 0.05) [10]. Similar outcomes were obtained in another center, but that research was a cohort study [8].

Interestingly, the White Test has intraoperatively revealed bile leakages in 37.2% of cases. This rate was significantly higher than the postoperative bile leakage rate in our control group (8.3%) and rates reported in the literature [32]. This raises the question of whether many bile leakages diagnosed by the White test could have been ordinarily clinically insignificant and did not actually need management intraoperatively after liver resection. Another hypothesis may attribute the high rate of intraoperative bile leakages diagnosed by the White Test to an induction of increased pressure in the biliary system when carrying out the White Test. These speculative reasons for the high rate of bile leakages revealed by the White test require further specifically designed studies.

The White Test can be less practical in the case of laparoscopic liver resection; nevertheless, the method can be adapted to a minimally invasive surgical technique [33]. However, ICG-compatible equipment for laparoscopic surgery has a clear trend of becoming a standard in high-income countries [34]; thus, the ICG method tends to be more applicable in the laparoscopic setting.

In this study, we did not demonstrate a significant reduction in the frequency of biliary complications after the White Test application. The number of postoperative bile leakage cases did not significantly differ between the group that had undergone the White Test and the control group (7% and 8.3%, p > 0.05). The negative White Test and additional preventive measures in case of a positive result did not guarantee the absence of bile leakage in the postoperative period. In addition, the operative time was approximately 15 min longer in the White Test group, but this difference was not significant (possibly due to statistical error, type 2).

This study has limitations. The relatively small number of patients included in this study can explain the lack of the White Test’s effectiveness in bile leakage prevention after liver resection. Besides, the study did not recruit the planned number of patients, and it randomly had more patients in the study group than in the control group. These factors and the low incidence of biliary complications in specialized centers may contribute to the possibility of statistical error, type 2. In addition, in recent years, technological improvements in the methods of intraoperative bile leakage control have been made that might potentially improve these methods, including both the White Test and especially ICG methods, which have blossomed tremendously [31, 34]. The present study is reported with a considerable procrastination time frame, which can be considered a limitation too.