Discussion
In 1949, Mallory
et al. [
15] described a single case of HCC invading the gall bladder and obstructing extrahepatic bile ducts. In 1975 Lin
et al. [
16] described eight patients and classified icteric type hepatoma. Since then, there are several reports concerning HCC with BDT have been published [
1‐
7]. The outcome in patients who received palliative treatment was poor, with a mean survival time of less than 5 months [
17‐
19]. Surgical treatment is the only way that possibly cures the patients [
19,
20]. However, the resectability rate of such tumors was very low in early reports, ranged only from 2% to 13.2% [
21]. In recent years, with progress in imaging diagnosis and preoperative management, the number of resectable cases were increased remarkably [
4‐
7,
21].
HCC invades into biliary system through one of the following three mechanisms: (1) the tumor may grow continuously in a distal fashion, filling the entire extrahepatic biliary system with a solid cast of tumor; (2) a fragment of necrotic tumor may separate from the proximal intraductal growth, migrating to the distal common bile duct and causing obstruction; or (3) hemorrhage from the tumor may partially or completely fill the biliary tree with blood clots [
18]. Generally, the tumor thrombus was not adherent to the bile duct wall so it could be removed easily. Tumor thrombi rarely invade the walls of the large bile ducts around the hepatic hilus. Therefore, liver resection of the involved hepatic segments with thrombectomy through a choledochotomy is a rational technique for curative resection [
2]. The indications for extrahepatic bile duct resection were macroscopic tumor invasion of the large bile ducts around the hepatic hilus [
2].
Venous invasion is a well-established prognostic indicator of HCC [
22,
23]. By contrast, whether BTT have a significant impact on the prognosis of HCC remain controversial. Shiomi
et al. [
2] reported that the 3- and 5-year survival rates were 47% and 28%, respectively, in 17 patients with BTT, similar to those achieved in 115 patients without BTT. Satoh
et al. [
5] also found that there were no significant differences in survival between patients with BTT and those without BTT. These data suggest that BTT in HCC patients might have lower aggressive potential and be less important as a prognostic factor. Paradoxically, Yeh
et al. [
6] in an analysis of 17 patients who underwent resection, reported that the overall survival was worse in patients with BTT, compared with those without BTT. In another recent study, Ikenaga
et al. [
7] reported that the median survival time of HCC patients with BTT after surgery was significantly shorter than that of those without thrombi (11.4 vs. 56.1 months,
P = 0.002).
Currently, there are two surgical staging systems, which were developed based on the analysis of patients who received hepatic resection: one from the Liver Cancer Study Group of Japan (LCSGJ) and another from the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC). In LCSGJ system, presence of BTT was considered as an indicator of "advanced stage" of HCC. A study from Japan reported that the prognostic stratification ability of the LCSGJ staging system is superior to that of the AJCC/UICC staging system and that the BTT is the strongest prognostic factor for HCC [
24]. This idea is supported by the results in our present study showing that the resection of HCC with BTT results in a significantly worse survival outcome compared with hepatic resection of HCC without BTT.
In current study, the incidence of microscopic vascular invasion [
13,
23], tumor capsule absence [
25,
26], high Edmondson- Steiner grade [
22,
27,
28], and high level of GGT [
29], unfavorable clinical prognostic factors, in group I were significantly higher than the respective factors in group II. Therefore, these factors may account for the poor prognosis in patients with BTT, at least in part. In addition, the incidences of CA19-9 > 37 U/ml, elevation of total bilirubin, ALT, AST, and ALP in group I were significantly higher than those in group II, which may be related to obstructive jaundice caused by BTT.
Previous studies have indicated that the HCC patients with BTT had smaller tumors and a higher percentage of a tumor size ≤ 5 cm than those without BTT [
6]. Similarly, in this study, the incidence of tumor size ≤ 5 cm tended to be higher in group I, despite this result did not reach statistical significance due to the small number of patients. Although the exact mechanism remains unknown, some authors have suggested that a BTT in HCC tends to grow faster than the primary tumor itself [
4].
Tumor recurrence remains the major cause of death after resection for HCC [
30,
31]. Despite similar treatments, the prognosis for patients with early recurrence was worse than that of patients with late recurrence [
14]. Qin
et al. [
4] reported that 14 patients with BTT (14/28, 50.0%) were found intrahepatic HCC recurrence within 1 year after operation. Ikenaga
et al. [
7] reported that 53% of patients suffered recurrences in the remnant liver within 3 months after surgery. In current study, patients with BTT developed early recurrence after resection more frequently.
We found seven patients in group I recurrenced with BTT again. Recurrence in the liver remnant could results from either intrahepatic metastasis from the primary tumor or multicentric occurrence. Intrahepatic metastasis is an important mechanism of early intrahepatic recurrence after resection of HCC. Spreading via the portal vein is considered the main route of intrahepatic metastasis [
14,
32]. In current study, 17 patients (62.9%) in the group I had microscopic vascular invasion. However, nine of the other ten cases without venous invasion also developed early recurrence. Similar results had been published previously by Ikenaga
et al. [
7], who found that two patients with BTT without portal vein invasion suffered multiple recurrences in the remnant liver. The authors speculate that HCC invasion biliary system may be another route of intrahepatic metastasis.
Esaki
et al. [
8] reported that HCC patients with macroscopic BTT had a better postoperative survival than patients with microscopic BTT. But Ikenaga
et al. [
7] found that the prognosis was similar between two groups. In current study, statistical analysis was limited by the too small population with microscopic BTT.
The experience with orthotopic liver transplantation (OLT) in patients with BTT is limited. There were only five cases reported in the English literatures [
21,
33]. Of these patients, one died 20 months after OLT due to multiple intrahepatic recurrences, one developed carcinoma recurrence at the lower end of the common bile duct 27 months after OLT. The other three patients were alive without evidence of recurrence during the follow-up period (17.6 to 28.1 months). These results suggest that OLT may be a treatment option for HCC with BDT in selected cases.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
WS participated in the design and coordination of the study, carried out the critical appraisal of studies and wrote the manuscript. CS, ZL, and YZ developed the literature search, carried out the extraction of data, assisted in the critical appraisal of included studies and assisted in writing up. WS and CS carried out the statistical analysis of studies. JY and YZ interpreted data, corrected and approve the manuscript. All authors read and approved the final manuscript.