Extent of Intrahepatic Infiltration of Perihilar Cholangiocarcinoma

Pattern and Extent of Intrahepatic Infiltration of Perihilar Cholangiocarcinoma - A Liver Panoramic Digital Pathological Study

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. This prospective study included 62 participants 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.

Study Overview

• Status: Completed
• Conditions: Perihilar Cholangiocarcinoma

Detailed Description

Perihilar cholangiocarcinoma (PHCC) is the most common type of bile duct malignancy, and radical surgical resection is the most effective treatment. The extent and characteristics of the intrahepatic infiltration of PHCC remain unclear, leading to controversy about the extent of liver resection for PHCC. The expert consensus statement of PHCC recommends tumor-invaded lobectomy as the standard procedure for liver resection, however, many studies recommend major hepatectomy (hemihepatectomy or trisectionectomy). Recently, minor hepatectomy has emerged for PHCC, such as resection of segment IVB+V and perihilar combined with segment I resection; however, the efficacy remains controversial. To determine the extent and characteristics of intrahepatic infiltration of PHCC, the investigators constructed a whole-mount digital liver pathology system (WDLPS) that allows the tumor and surrounding liver tissue from major hepatectomy specimens to be displayed in one large section, which could localize the margin of the main tumor and observe the distribution of adenocarcinoma panoramically. In addition, digital measurement was used to accurately measure the range of intrahepatic infiltration to guide the scope of hepatectomy. From April 2018 to December 2021, 62 participants were diagnosed for PHCC based on clinical manifestations, imaging, and pathological findings. All participants underwent hemihepatectomy or trisectionectomy combined with caudate lobectomy. Skeletonization resection of the hepatoduodenal ligament, including dissection of the regional lymph nodes, was performed from the duodenum to the liver. Clinical and pathological indicators of the participants were collected. Portal vein and hepatic artery invasion were defined as the primary or secondary branch in the resected side or the reserved side which was invaded. In this study, the investigators established a WDLPS to study the intrahepatic invasion range and pathway of PHCC through the major hepatectomy specimens panoramically. The distal intrahepatic infiltration (DIHI) and radial liver invasion (RLI) were important components of intrahepatic infiltration of PHCC explored by WDLPS. RLI distance was defined as the maximum straight-line distance from the infiltrated liver parenchyma to the hepatic hilar plate. DIHI was defined as the intrahepatic infiltration greater than 1 cm from the margin of the main tumor. The distance between the DIHI and the margin of the main tumor was recorded. Categorical variables are expressed as percentages (%) and the difference were tested using the chi-squared test or Fisher's exact test. Continuous variables are presented in the form of mean±standard deviation and were tested using the t-test or Mann-Whitney U test, when appropriate. Relapse-free survival (RFS) and Overall survival (OS) were estimated using the Kaplan-Meier method, and differences between groups were assessed by the log-rank test. In addition, the investigators estimated restricted mean survival time (RMST) without a truncation time and RMST differences (ΔRMSTs) for RFS and OS between treatment groups to provide clinically relevant intuitive estimation. Statistical analyses were performed using the SPSS software (version 26.0, SPSS Inc., IBM, Armonk, NY, USA) and R (version 4.2.2.R Core Team.2022).

• Study Type: Observational
• Enrollment (Actual): 62

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 102218
      • Beijing Tsinghua Chang Gung Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients were diagnosed for PHCC based on clinical manifestations, imaging, and pathological findings. All patients underwent hemihepatectomy or trisectionectomy combined with caudate lobectomy. Skeletonization resection of the hepatoduodenal ligament, including dissection of the regional lymph nodes, was performed from the duodenum to the liver. Clinical and pathological indicators of the patients were collected. Portal vein and hepatic artery invasion were defined as the primary or secondary branch in the resected side or the reserved side which was invaded.

Description

Inclusion Criteria:

1. Patients were diagnosed for PHCC based on clinical manifestations, imaging, and pathological findings.
2. Hepatectomy was performed.
3. WDLPS was successfully produced.

Exclusion Criteria:

1. Not PHCC patients.
2. Patients with PHCC did not undergo hepatectomy.
3. WDLPS was not successfully produced.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
No RLI vs RLI; No RLI: PHCC patients without RLI. RLI: PHCC patients with RLI.
No DIHI vs DIHI; No DIHI: PHCC patients without DIHI. DIHI: PHCC patients with DIHI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-free survival (RFS).	Refers to the survival time of a PHCC patient without recurrence of PHCC for a period of time after surgical treatment.	RFS as of December 2023

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS).	Refers to the time from the start of surgical treatment to death or the last follow-up of a PHCC patient.	OS as of December 2023

Collaborators and Investigators

• Sponsor: Beijing Tsinghua Chang Gung Hospital
• Investigators: Principal Investigator: Shuo Jin, PhD, Beijing Tsinghua Changgung Hospital affiliated to Tsinghua University

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2018
• Primary Completion (Actual): December 22, 2021
• Study Completion (Actual): December 22, 2021

Study Registration Dates

• First Submitted: April 4, 2024
• First Submitted That Met QC Criteria: April 9, 2024
• First Posted (Actual): April 10, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Klatskin Tumor
• Other Study ID Numbers: A01263

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is not a plan to make IPD available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No