Pattern and extent of intrahepatic infiltration of perihilar cholangiocarcinoma - a case-control study based on liver panoramic digital pathology

Abstract

Background: The extent of intrahepatic infiltration of perihilar cholangiocarcinoma (PHCC) remains unclear. This research aimed to explore the pattern and extent of intrahepatic infiltration of PHCC to guide surgical treatment and pathological research.

Materials and methods: This study included 62 patients diagnosed with PHCC who underwent major hepatectomy. A whole-mount digital liver pathology system (WDLPS) for hepatectomy specimens greater than 10×10 cm was used to panoramically assess the intrahepatic infiltration extent of PHCC.

Results: The distal intrahepatic infiltration (DIHI) and radial liver invasion (RLI) were important parts of intrahepatic infiltration for PHCC explored by WDLPS. The study confirmed that 75.8% of PHCCs had RLI and the infiltration distance in all patients were within 15 000 µm, 62.9% of PHCCs had DIHI greater than 1 cm away from the main tumor in the liver parenchyma. The recurrence-free survival rates and overall survival rates of patients with DIHI were poorer than the patients without DIHI ( P <0.0001, P =0.0038). Arterial invasion on the resected side could be an excellent predictor. A total of 105 liver lobes were resected from 62 PHCC patients. The invasion rates of the left lateral, left medial, right anterior, and right posterior lobe of PHCC were 79%, 100%, 100%, and 69%, respectively.

Conclusion: The presence of DIHI in most PHCCs was a significant factor for the poor survival. Based on the extent of intrahepatic infiltration, minor hepatectomy was not suitable as the curative surgery for PHCC. Major hepatectomy and liver transplantation were the ideal radical treatment.

Trial registration: ClinicalTrials.gov NCT06357117.

Graphical abstract

Figure 1

Whole-mount digital liver pathology system (WDLPS) of perihilar cholangiocarcinoma (PHCC) hemihepatectomy specimen after hematoxylin and eosin (H&E) staining. (A) Panoramic H&E staining of pathological sections of a right hemihepatectomy specimen. Scale bar, 5000 μm. (B) Measurement example of radial liver invasion (RLI) range. The blue arrow shows the distance of RLI. Scale bar, 500 μm. (C) Distal intrahepatic infiltration (DIHI) distributed in the right anterior lobe. Scale bar, 50 μm. (D) DIHI distributed in the right posterior lobe. Scale bar, 50 μm. (E) DIHI adjacent to the liver resection margin. Scale bar, 50 μm. (F) The margin of the main tumor located by WDLPS. Scale bar, 1000 μm. (G) DIHI distributed in the caudate lobe. Scale bar, 50 μm.

Figure 2

Pattern and extent of intrahepatic infiltration of perihilar cholangiocarcinoma (PHCC). (A) Distance of radial liver invasion (RLI). (B) Distance of distal intrahepatic infiltration (DIHI).

Figure 3

The landscape of invaded liver lobe of perihilar cholangiocarcinoma (PHCC). (A) The invasion rates of the left lateral, left medial, right anterior, and right posterior lobe of PHCC total. (B) The invasion rates of the patients with DIHI from the left lateral lobe to the right posterior lobe. (C) The invasion rates of the patients without DIHI from the left lateral lobe to the right posterior lobe.

Figure 4

Survival analysis of perihilar cholangiocarcinoma (PHCC). (A) Recurrence-free survival (RFS) for patients with and without radial liver invasion (RLI, P=0.037). (B) Overall survival (OS) for patients with and without RLI (P=0.011). (C) RFS for patients with and without distal intrahepatic infiltration (DIHI, P<0.0001). (D) OS for patients with and without DIHI (P=0.0038). (E, F) Recurrence of positions in patients with and without RLI and DIHI.