Effectiveness of additional resection of the invasive cancer-positive proximal bile duct margin in cases of hilar cholangiocarcinoma

Abstract

Background: The survival benefits of additional resection of the positive proximal ductal margin (PM) in hilar cholangiocarcinoma (HCCA) remains controversial. This retrospective study investigated the effectiveness of additional resection of the invasive cancer PM under different levels of preoperative carbohydrate antigen 19-9 (CA19-9).

Methods: Patients who underwent hepatectomy for HCCA from 2000 to 2017 were analyzed. Surgical variables, resection margin status, length of the PM (LPM), prognostic factors, and survival were evaluated.

Results: A total of 228 patients were enrolled: 175 PM(-) without additional resection patients (group A), 21 PM(-) after additional resection (group B), 16 PM(+) without additional resection (group C), and 16 PM(+) after additional resection (group D). The median survival of group B (20.99 months) was similar to that of group A (23.00 months; P=0.16), and both were significantly better than those of group C (11.60 months) and D (9.50 months), especially when preoperative CA19-9>150 U/mL (P<0.05). The survival of patients with an LPM >10 mm was significantly better compared with those with an LPM ≤10 mm, especially when preoperative CA19-9 was >150 U/mL (P<0.05). Only in the LPM >10 mm group, the survival of group B was comparable with that of group A (P>0.05).

Conclusions: HCCA patients could get a survival benefit from a negative PM resulting from additional resection. Survival could be comparable with that of negative PM without additional resection among HCCA patients. An LPM >10 mm is possibly more associated with better survival compared with whether additional resection of the positive PM is performed under different levels of preoperative CA19-9.

Keywords: Klatskin tumor; antigens, neoplasm; bile ducts; carbohydrate antigen 19-9 (CA19-9); margins of excision.

Figure 1

Program of the specimens submitted for histopathologic analysis and the grouping method for patients. (A) The duct margin was submitted for intraoperative frozen section analysis. An additional margin was submitted when a positive duct margin was found at the time of frozen section analysis. The specimen margin was submitted for permanent histopathology only. The distal margin was taken from the distal common bile duct; (B) distribution of patients undergoing radical resection of hilar cholangiocarcinoma based on bile duct margin status, as diagnosed by intraoperative frozen-section assessment and final permanent section pathologic examination. *, indicates that a total of 205 patients were thought to have negative final duct margins with intraoperative frozen section analysis.

Figure 2

Survival depending on proximal bile duct margin (PM) status.

Figure 3

Overall survival for the enrolled population according to the final proximal ductal margin (PM) status.

Figure 4

Overall survival according to the final proximal ductal margin (PM) status with the study population stratified according to CA19-9 ≤150.0 or CA19-9 >150.0 U/mL (A,B), and after separating R1 resection patients individually (C,D).

Figure 5

Overall survival according to the length between the gross tumor and the proximal ductal margin (LPM) in patients grouped according to their different levels of pre-CA19-9.

Figure 6

Overall survival according to the final proximal ductal margin (PM) status with the study population stratified by the final length of proximal ductal margin (LPM): LPM ≤10 mm or LPM >10 mm (A,B), and after separating by R1 resection (C,D).

Figure 7

The survival of patients with an LPM >10 mm was significant better than that of the patients with LPM ≤10 mm (P<0.05), except for those patients with PM(+) (P>0.05).

Figure 8

Overall survival for the entire study population according to the length between gross tumor and proximal bile duct resection margin (LPM).

Figure 9

Overall survival according to the final length of proximal ductal margin (LPM) with the study population stratified according to preCA19-9 ≤150.0 U/mL or pre-CA19-9>150.0 U/mL.