Influence of surgical margin width on survival rate after resection of intrahepatic cholangiocarcinoma: a systematic review and meta-analysis

Abstract

Objectives: Hepatectomy is the best treatment for patients with intrahepatic cholangiocarcinoma (ICC) at present, but there has been controversy about the width of surgical margins. In this study, we systematically investigated the effects of different surgical margin widths on the prognosis of patients with ICC undergoing hepatectomy.

Design: Systematic review and meta-analysis.

Data sources: PubMed, Embase and Web of Science databases were systematically searched from inception to June 2022.

Eligibility criteria: Cohort studies reported in English with patients who underwent negative marginal (R0) resection were included. The effects of surgical margin width on overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) in patients with ICC were assessed.

Data extraction and synthesis: Two investigators independently conducted literature screening and data extraction. Risk of bias was assessed using funnel plots and quality was assessed by the Newcastle-Ottawa Scale. Forest plots of HRs and their 95% CIs for outcome indicators were plotted. Heterogeneity was assessed and determined quantitatively using I², and the stability of the study results was evaluated using sensitivity analysis. Analyses were performed using Stata software.

Results: Nine studies were included. With the wide margin group (≥10 mm) as the control, pooled HR of OS in the narrow margin group (<10 mm) was 1.54 (95% CI 1.34 to 1.77). HRs of OS in three subgroups where the margin was less than 5 mm ranged from 5 mm to 9 mm, or was less than 10 mm in length were 1.88 (1.45 to 2.42), 1.33 (1.03 to 1.72) and 1.49 (1.20 to 1.84), respectively. Pooled HR of DFS in the narrow margin group (<10 mm) was 1.51 (1.14 to 2.00). Pooled HR of RFS in the narrow margin group (<10 mm) was 1.35 (1.19 to 1.54). HRs of RFS in three subgroups where the margin was less than 5 mm ranged from 5 mm to 9 mm, or was less than 10 mm in length were 1.38 (1.07 to 1.78), 1.39 (1.11 to 1.74) and 1.30 (1.06 to 1.60), respectively. Neither lymph node lesions (HR 1.44, 95% CI 1.22 to 1.70) nor lymph node invasion (2.14, 1.39 to 3.28) was favourable for postoperative OS in patients with ICC. Lymph node metastasis (1.31, 1.09 to 1.57) was unfavourable for RFS in patients with ICC.

Conclusion: Patients with ICC who underwent curative hepatectomy with a negative margin ≥10 mm may have a long-term survival advantage, but lymph node dissection also needs to be considered. In addition, tumour-related pathological features need to be explored to see if they affect the surgical outcome of R0 margins.

Keywords: Hepatobiliary disease; Hepatobiliary tumours; Hepatology.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart for the included studies.

Figure 2

Results of HR pooled analysis of the overall survival rate of the included studies (with the wide margin group ≥10 mm as the control).

Figure 3

Results of HR pooled analysis of disease-free survival in the included studies (with the wide margin group ≥10 mm as the control).

Figure 4

Results of HR pooled analysis of recurrence-free survival in the included studies (with the wide margin group ≥10 mm as the control).

Figure 5

Results of HR pooled analysis of lymph node lesions on overall survival in patients with intrahepatic cholangiocarcinoma (with the wide margin group ≥10 mm as the control).

Figure 6

Results of HR pooled analysis of lymph node invasion on overall survival in patients with intrahepatic cholangiocarcinoma (with the wide margin group ≥10 mm as the control).

Figure 7

Results of HR pooled analysis of lymph node metastasis on recurrence-free survival in patients with intrahepatic cholangiocarcinoma (with the wide margin group ≥10 mm as the control).

Figure 8

Sensitivity analysis of overall survival after leave-one-out analyses.

Figure 9

Sensitivity analysis of recurrence-free survival after leave-one-out analyses.

Figure 10

Funnel plot of the relationship between surgical margin width and overall survival in patients with intrahepatic cholangiocarcinoma.

Figure 11

Funnel plot of the relationship between surgical margin width and recurrence-free survival in patients with intrahepatic cholangiocarcinoma.