Study of Liver Resection With Versus Without Hepatic Inflow Occlusion for the HBV-related HCC

Study Overview
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Brief Summary
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The study aims to compare the perioperative and long-term outcomes of liver resection for HBV-related HCC with versus without hepatic inflow occlusion.

Detailed Description
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High prevalence of hepatitis B virus (HBV) imposes a huge burden of hepatocellular carcinoma (HCC) in Asia. Liver resection remains the mainstay of treatment for HCC. Hepatic inflow occlusion, known as the Pringle maneuver, is most commonly used to reduce blood loss during liver parenchymal transection. A major issue about this maneuver is the ischemia-reperfusion injury to the remnant liver. And the hemodynamic disturbance to the tumor-bearing liver remains an oncologic concern. Given the technical advances in living donor liver transplantation, vascular occlusion can be avoided in liver resection by experienced hands. This study aims to compare the perioperative and long-term outcomes of liver resection for HBV-related HCC without versus with hepatic inflow occlusion. This study will include eligible patients with HBV-related HCC elected for liver resection. 57 patients will be enrolled in each randomized arm to detect a 20% difference in the serum level of total bilirubin on postoperative day 5 (80% power and α = 0.05). The secondary endpoints include procedural parameters, perioperative liver function and inflammatory response, postoperative morbidity and mortality, and long-term outcomes. Patients will be followed for up to five years. Data will be statistically analyzed on an intention-to-treat basis. This prospective randomized controlled trial is designed to evaluate the feasibility of liver resections for HBV-related HCC without vascular occlusion. Clinical implication of its outcomes may change the present surgical practice and fill the oncologic gaps therein.

Official Title
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Short- and Long-term Outcomes of Liver Resection With Versus Without Hepatic Inflow Occlusion for the Hepatitis B Virus-related Hepatocellular Carcinoma: a Prospective Randomized Controlled Trial

Conditions
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Liver Cancer, Surgery

Intervention / Treatment
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* Procedure: non-occlusion technique


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elective liver resection due to HBV-related HCC with Barcelona-Clinic Liver Cancer (BCLC) staging 0 or A; Child-Pugh classified A with or without cirrhosis, or reversed to A from B after conventional therapy; Tumors located either in the left or right hemiliver; Resection extent was a hemi-hepatectomy or less; Informed consent. Exclusion Criteria: Having comorbidity that contraindicates surgery; Participation in concurrent interventional trials with interference to this study; Eligible for laparoscopic hepatectomy; Requiring concomitant procedures, such as digestive, vascular or biliary reconstruction; Lack of compliance for treatment or future follow-up.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Hx with hepatic inflow occlusion<br>Hepatectomy is carried out using Pringle maneuver in cycles of 15 minutes clamping + 5 minutes unclamping of the hepatoduodenal ligament. | |
| Experimental: Hx with non-occlusion technique<br>Hepatectomy without hepatic inflow occlusion (non-occlusion technique) | Procedure: non-occlusion technique<br>* Hepatectomy is carried out without hepatic inflow control. (non-occlusion technique)<br>* Other names: hepatectomy without hepatic inflow occlusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum total bilirubin on postoperative day 5 | Postoperative liver insufficiency characterized by the serum total bilirubin on POD 5. | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoperative blood loss | Total blood loss from the incision to the closure of abdomen | Entire operation duration | 
| Requirement of blood transfusion | The amount of intraoperative blood transfusion | Entire operation duration | 
| Operative time | The time from induction of anesthesia to the closure of abdomen | Entire operation duration | 
| Postoperative intensive-care unit (ICU) stay | Duration of stay in ICU | Duration of stay in ICU | 
| Hospital stay | Duration of hospital stay | Duration of hospital stay | 
| Total hospital expenditure | Total costs during hospital stay | Duration of hospital stay | 
| Perioperative systemic inflammatory response | Perioperative systemic inflammatory response is characterized by elevated serum level of tumor necrosis factor-α (TNF-α), interleukins (IL)-1α, 2, 6, 8 and 10, procalcitonin (PCT) and C-reactive protein (CRP) at different time points. | an expected average of 7 days | 
| Postoperative morbi-mortality | Postoperative morbi-mortality is characterized by postoperative complication and its severity based on Clavien-Dindo classification and in-hospital mortality | an expected average of 12 days in hospital | 
| Long-term oncologic outcomes | 1, 3, 5-year tumor recurrence rate | 5 years after operation | 
| Long-term survival | 1, 3, 5-year overall survival (OS) and disease (tumor)-free survival (DFS) | 5 years after operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver resection, blood inflow control, ischemia-reperfusion injury, inflammatory response, randomized controlled trial