Xiaobin et al. BMC Cancer 2012, 12:340 http://www.biomedcentral.com/1471-2407/12/340 (power) of 0.800. The Type I error probability associated with this test of the hypothesis is 0.05. Data for primary and secondary outcome measures will be analyzed using the SPSS statistical software pack- age (SPSS UK Ltd., Woking, U.K.). Analysis will include standard descriptive statistics, Student’s t tests, correl- ation and regression, and two-way (group x time) repeated measures ANOVA to examine differences be- tween the groups over time. Survival analysis will be per- formed. Statistical significance will be set at p < 0.05and all tests will be two-tailed. Subgroup stratified analysis will be performed according to tumor size, tumor encap- sulation, Edmondson’s grade, HBV load, ischemic time, blood loss, and transfusion. The intention-to-treat ana- lysis will be used for the patients whose portal triad clamping was changed due to safety reasons. Randomization, stratification, and blinding This is a randomized multicenter study. After giving informed consent and being enrolled in the study, patients will be randomized into different groups in the operating room after surgical exploration. The permuted-blocks randomization protocol will com- prise five separate randomization lists, one for each participating hospital, and will be centrally managed by the Clinical Trial Center of the lead hospital, the Third Military Medical University. When an eligible case is enrolled, the Clinical Trial Center will be called and a randomization number will be assigned according to the designated list. Because there are two groups in this trial, the block sizes will be 4, 6, and 8 and will be randomly assigned. Patients will be stratified by site and randomized in a ratio of 1:1 into the two groups. Patients and outcome assessors will be blinded to achieve a minimum bias. Endpoints The primary trial endpoint will be tumor recurrence diagnosed by enhanced CT scan or serum alpha- fetoprotein level. Secondary objectives are to examine overall survival, blood loss, duration of operation, re- quirement for blood transfusion, length of hospital stay, and morbidity rate. The formal end of the study will be at the end of the 3-year follow-up period of the last pa- tient to be enrolled. All these parameters will be recorded prospectively as part of the study protocol. Final evaluation of the primary and secondary endpoints of the study will be performed 1 year after enrollment of the last patient. Clinical evaluation The clinical evaluation of patients will consist of three stages: preoperative, intraoperative, and postoperative. Page 5 of 8 During the preoperative stage, the surgeon will evaluate whether curative resection of the tumor can be per- formed with and without the Pringle maneuver. For safety reasons, the operating surgeon can change the portal triad clamping status at any time during the oper- ation. If the portal triad clamping is changed, the patient will still be included in the intention-to-treat analysis. If a pathological diagnosis of non-primary HCC is made postoperatively by two different professionals who were blinded to the treatment, the patient will be excluded. Safety aspects and adverse advents Both arms of this trial follow well-established proce- dures, which are widely used in many surgical centers allover the world. No specific side effects are expected other than the known complications of hepatectomy. The operating surgeon can change the portal triad clamping protocol at any time during the operation if necessary to ensure safety. All adverse events during the hospital stay and follow-up will be recorded for correl- ation analysis. Ethics and informed consent The final version of the study protocol was approved by the ethics committee of Southwest Hospital, Third Mili- tary Medical University. This protocol follows all requirements of the recent German version of the Dec- laration of Helsinki (Somerset West Version, 1996) and is in accordance with the principles of Good Clinical Practice guidelines. The trial has been initiated and will be carried out following all local legal and regulatory requirements. The medical secrecy act will also be fol- lowed. Prior to enrollment in the study, written informed consent will be obtained from each patient in oral and written form. Any measures specifically required only for the clinical trial will not be undertaken until valid consent has been obtained. Extensive infor- mation about the intent of the study, the interventions in each group, the potential associated risks, and poten- tial alternative therapies will be fully discussed with each patient. Patients will be also informed that participation is voluntary and can be withdrawn at any time without prejudicing their subsequent care. Patients will be informed of the strict confidentiality of their personal data collected for this trial, and that their medical records may be reviewed for trial purposes by authorized individuals. Follow-up Patients who have completed the interventions will be included in the standard follow-up program. Follow- up visits will be at 1, 3, 6, 9, and 12 months and then every 6 months until 3 years after their operation. Each visit will include physical examination, tumor