Laparoscopic Versus Open Major Hepatectomy for HCC Hepatectomy for Hepatocellular Carcinoma

Summary

Background: Hepatocellular carcinoma (HCC) is the sixth most common malignancy in the world. Major hepatectomy (resection of \> 3 liver segments) is needed if tumor is close to major blood vessels within liver. Despite low mortality, open major hepatectomy (OMH) is associated with high tumor recurrence rate, and short survival. Immunosuppression due to surgical stress and blood transfusion, and dissemination of tumor cells because of tumor manipulation all contribute to tumor recurrence.

Laparoscopic major hepatectomy (LMH) is a newly developed minimally invasive technique for HCC. Apart from less wound problems and shorter recovery time than open surgery, LMH may have potential oncological benefits of prolonging survival. These could be related to the reduced intraoperative blood loss, less immunosuppression due to surgical stress, and less tumor manipulation. Hence, LMH could be a better treatment option than OMH for HCC.

Objectives:

1. To compare the long-term oncological outcome between laparoscopic and open major hepatectomy for patients with hepatocellular carcinoma
2. To achieve the comparison under the study design of multi-center randomized trial involving 5 high-volume centers in Asia-Pacific region
3. Primary outcome is 2-year recurrence-free survival.
4. Secondary outcome as intraoperative blood loss, blood transfusion, 30-day and hospital mortality, postoperative morbidities according Clavien-Dindo classification, hospital stay, quality of life, overall and recurrence-free survival rates up to 5 years after surgery
5. To compare the perioperative changes in stress-related cytokines, which help to clarify the stress response and immunosuppression and their correlations with overall and recurrence-free survival rates

Hypothesis: Laparoscopic major hepatectomy is associated with less surgical stress, less immunosuppression and thus less tumor recurrence and better survival than open major hepatectomy.

Study design: This is an open-labelled prospective randomized trial involving 106 patients in each treatment arm (Total number of patients recruited: 212). The study will involve 5 surgery centers in Asia-Pacific region (2 centers in Hong Kong, 3 centers in Mainland China Foshan, Shanghai and Sichuan).

Subjects: Patients with HCC undergone major hepatectomy. Recruitment centres involved:

1. Department of Surgery, The Chinese University of Hong Kong
2. Department of Surgery, Kwong Wah Hospital, Hong Kong
3. Department of Surgery, West China Medical School of Sichuan University
4. Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital \& Institute, Second Military Medical University
5. Department of Surgery, The First People's Hospital of Foshan

Intervention: Consented patient will be randomized 1:1 to one of the two treatment arms:

1. Laparoscopic group: LMH
2. Open group: OMH The randomization schedule will be generated by the Clinical Trials Centre (CTC) of principle investigator's center, prior to the start of the study.

Main outcome measure: The primary objective is to test the hypothesis that LMH is associated with less surgical stress, less immunosuppression and thus less tumor recurrence and better survival than OMH. The primary outcome measure is 2-year recurrence-free survival.

Data analysis: Statistical plan and data monitoring Statistical analysis will be performed using SPSS version 11.0 (SPSS Inc., Chicago, Ill). The 2-year recurrence-free survival (primary outcome) will be evaluated by Kaplan-Meier method and compared by the log-rank test between studied groups.

Expected results: The result of this study provides level 1 evidence on the best treatment option for HCC, which needs major hepatectomy. Such information will influence the evidence-based policy in professional practice in the management algorithm for HCC. Since postoperative complications and tumor recurrence are substantial after OMH, potential benefits of LMH tested in this study will help to alleviate these problems.

Conditions

• Hepatocellular Carcinoma

Interventions

PROCEDURE

Open or laparoscopic surgery

Patients, with their consent, will be recruited to participate by investigators after considering the inclusion and exclusion criteria. Treatment allocation to the eligible patients will follow a randomization schedule. A total of 212 subjects will be randomized 1:1 to one of the two treatment arms: 1. Laparoscopic group: LMH 2. Open group: OMH

Sponsors & Collaborators

• Health and Medicine Research Fund

  collaborator UNKNOWN

• Chinese University of Hong Kong

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-12-01

Primary Completion

2024-11-30

Completion

2024-11-30

Countries

• Hong Kong

Study Locations