Laparoscopic Versus Open Major Hepatectomy for HCC Hepatectomy for Hepatocellular Carcinoma

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.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Diagnosis of HCC is in accordance to the diagnostic criteria for HCC used by the European Association for the Study of the Liver. HCC was diagnosed when the radiologic imaging techniques (spiral contrasted CT scan or contrasted MRI) showed typical features of HCC (contrast enhancement in the arterial phase and rapid wash-out of contrast in the venous or delayed phase) and/or elevated serum alpha fetoprotein (AFP) level.
* HCC of maximum diameter up to 10 cm; Single or multiple tumor nodules confined to one liver lobe according to the previous reported series
* Major hepatectomy (resection of \> 3 Couinaud's segments) is required as judged by hepatobiliary surgeons
* Absence of extrahepatic metastasis or radiological evidence of venous invasion of major portal vein or hepatic vein branches
* Child's A liver function
* Indocyanine green retention at 15 min (ICG-15) \< 15%
* Adequate future liver remnant (image-guided volumetry \> 35% of estimated standard liver volume)
* General condition fit for general anaesthesia

Exclusion Criteria:

* Tumors unfavorable for major hepatectomy (e.g. bilobar tumors, main portal vein tumor thrombus and/or inadequate future liver volume)
* Previous treatment for HCC (e.g. transarterial chemoembolization, or chemotherapy)
* Tumors require combined hepatectomy and thermal ablation therapy

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