# Clinical implications of an intraoperative margin-positive distal bile duct in perihilar cholangiocarcinoma: international multicentre cohort study

## TL;DR

This study finds that re-surgery after a positive bile duct test during cholangiocarcinoma surgery can achieve good outcomes without increasing risks.

## Contribution

The study provides new evidence on the effectiveness and safety of intraoperative re-resection or pancreatoduodenectomy for margin-positive bile ducts in cholangiocarcinoma.

## Key findings

- 11.1% of patients had a positive distal bile duct frozen section.
- Re-resection or pancreatoduodenectomy achieved margin clearance in 69% of patients.
- Long-term survival was comparable to patients with primary negative margins.

## Abstract

The short- and long-term outcomes of intraoperative extension of the distal bile duct margin following a positive frozen section in patients with perihilar cholangiocarcinoma remain poorly characterized.

Between 1 January 2003 and 1 January 2023, consecutive patients at seven high-volume European hepatopancreatobiliary centres undergoing major hepatectomy for perihilar cholangiocarcinoma with frozen-section analysis of the distal bile duct and subsequent intraoperative management were included retrospectively. The primary endpoint was achievement of an overall R0 resection following distal bile duct re-resection or additional pancreatoduodenectomy after identification of a positive distal bile duct frozen section. Secondary endpoints included overall survival, disease-free survival, and major postoperative complications (Clavien–Dindo grade ≥ IIIa). Outcomes were reported as adjusted hazard ratios.

Of 785 patients undergoing major hepatectomy for perihilar cholangiocarcinoma, 594 underwent distal bile duct frozen-section analysis. A total of 66 (11.1%) intraoperative frozen sections were positive for invasive carcinoma, with an additional 7 (1.2%) false-negative findings. Distal bile duct re-resection was performed in 49 patients (74%), and 11 (16%) underwent additional pancreatoduodenectomy. Among these, 46 patients (69%) achieved distal bile duct margin clearance, with 30 (45%) ultimately attaining overall R0 resection. Overall survival was similar for patients who achieved overall R0 status via distal bile duct re-resection or pancreatoduodenectomy and those with overall R0 margins after primary negative distal bile duct frozen section (adjusted hazard ratio 0.84, 95% confidence interval 0.49 to 1.44; P = 0.536). Conversely, overall R1 resection was associated with significantly worse overall survival (adjusted hazard ratio 1.82, 1.43 to 2.33; P < 0.001). Complications graded ≥ IIIa and 90-day mortality did not differ significantly between groups undergoing distal bile duct re-resection, pancreatoduodenectomy or no intervention (P = 0.126 and P = 0.121, respectively).

In selected patients, re-resection or additional pancreatoduodenectomy after positive distal bile duct frozen-section analysis is associated with long-term survival without significantly increasing major morbidity or mortality.

In this multicentre cohort of 785 patients with perihilar cholangiocarcinoma, 11.1% had a positive distal bile duct frozen section. Re-resection or pancreatoduodenectomy achieved margin clearance in most patients without increasing major morbidity or mortality rates. Long-term survival was comparable to that among patients with primary negative margins, whereas R1 resections carried significantly worse outcomes.