Clinical trial NCT02525965: The Influence of Resection Margin on the Recurrence of Early-stage Hepatocellular Carcinoma
Official title: The Influence of Resection Margin on the Recurrence of Early-stage Hepatocellular Carcinoma After Hepatectomy: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hepatocellular Carcinoma
Keywords: Wide resection margin
Recurrence
Early-stage hepatocellular carcinoma
Lead sponsor: Eastern Hepatobiliary Surgery Hospital
Sponsor class: OTHER
First posted: 2015-08-18
Enrollment: 194
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Before the surgery, the investigators predict the risk of microvascular invasion (MVI) presence for the early-stage hepatocellular carcinoma according to the nomogram the investigators have created. Patients with a high risk of microvascular invasion were randomly chose to give the treatment of a wide resection margin, which establish an individualized anti-recurrence program based on the high-grade evidence-based medicine.

Detailed description: Although liver resection is still the first line of treatment for hepatocellular carcinoma (HCC) presently, 5-year overall recurrence rates \> 70%, the same with early-stage hepatocellular carcinoma, for some studies reported the rates \> 40%. Recurrence is also the first cause of death in these patients, so recurrence is the most important factors affecting surgical results of HCC. For the precaution of cancer recurrence, there are no proven techniques for clinical reference at present.

For now, there has been many controversies on the impact about the width of liver resection margin on curative effect. Poon has proven that there is no significant difference in recurrence rate between resection margin \> 1cm and resection margin \< 1cm. However, Shi et al published a randomized controlled trial: for patients with a solitary tumor, resection margin \> 2cm can reduce the recurrence rate after hepatectomy. This is also the only randomized clinical trial study which proves increaseing resection margin will benefit the clinical results at present. A meta analysis consist of 18 studies proves that whether the resection margin has a relationship with a benefit clinical result still needs a further verification.

On the other hand, because microvascular invasion (MVI) is the direct evidence of the micro metastasis in hepatocellular carcinoma, it will decrease recurrence rate for the patients with a high MVI risk, if the investigators increase the resection margin width during the surgery? Shanghai Eastern Hepatobiliary Surgery Hospital which the investigators affiliated with had ever conducted a retrospective analysis on consecutive 3263 patients with HCC hepatectomy, the results indicated that a wide resection margin（≥1cm）can benefit those patients with microvascular invasion , nevertheless, the benefit will not present if patients are without microvascular invasion.

Further and better proofs still needs to approval this consequence, of course. In the past，another study of the ours, published online in the Journal of the American Medical Association Surgery, established a nomogram to predict the presence of microvascular invasion in the early-stage hepatocellular carcinoma, it will efficiently predict the occurrence of microvascular invasion in the hepatocellular carcinoma (HCC) fulfilled the Milan criteria. In consideration of the above basis, the investigators will implement a randomized controlled trial to certificate whether it could really reduce the recurrence rate after liver resection for participants with a high MVI risk during the surgery, if the method participants chose is a wide resection margin.

Eligibility criteria: Inclusion Criteria:

* Male or female patients \> 18 years and \<=70 years of age.
* Diagnosed with HCC according to the criteria of American Association for the Study of Liver Diseases (AASLD).
* Fulfill the Milan criteria.
* High-risk of microvascular invasion (MVI).
* Nomogram score \>200.
* Performance status score is 0-1 before the surgery.
* Without or mild liver cirrhosis and the liver function is Child A class.
* Without any other treatments such as TACE、PEI、PRFA before the surgery.

Exclusion Criteria:

* Patients with macro tumor thrombus or extrahepatic metastasis.
* Patients with apparent cardiac, pulmonary, cerebral and renal dysfunction.
* Subjects accepting other trial drugs or participating in other clinical trials.
* Patients refuse to join our trial.
* Female with pregnancy or during the lactation period.

Primary outcomes:
measure: Overall survival rates of each group
timeFrame: 3 years
Secondary outcomes:
measure: Occurrence rate of recurrence of each group
timeFrame: 3 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Eastern hepatobilliary surgery hospital
state: Shanghai
Study officials:
affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
name: Shen Feng, MD
role: STUDY_CHAIR
References: