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Open Access Study protocol

Effect of the pringle maneuver on tumor recurrence of hepatocellular carcinoma after curative resection (EPTRH): a randomized, prospective, controlled multicenter trial

Feng Xiaobin1, Zheng Shuguo1, Zhou Jian3, Qiu Yudong4, Liang Lijian5, Ma Kuansheng1, Li Xiaowu1, Xia Feng1, Yi Dong6, Wang Shuguang1, Bie Ping1* and Dong Jiahong2*

Author Affiliations

1 Institute of hepatobiliary surgery, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China

2 Institute of hepatobiliary surgery, Chinese PLA General Hospital, Beijing, P. R. China

3 Institute of liver cancer, Zhongshan Hospital of Fudan University, Shanghai, P. R. China

4 Department of hepatobiliary surgery, Nanjing Drum Tower Hospital, Nanjing, P. R. China

5 Department of hepatobiliary surgery, the First Affiliated Hospital, Sun Yet-Sen University, Guangzhou, P. R. China

6 Department of health statistics, Third Military Medical University, Chongqing, 400038, P. R. China

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BMC Cancer 2012, 12:340  doi:10.1186/1471-2407-12-340

Published: 3 August 2012



Hepatic resection is currently still the best choice of therapeutic strategies for liver cancer, but the long-term survival rate after surgery is unsatisfactory. Most patients develop intra- and/or extrahepatic recurrence. The reasons for this high recurrence rate are not entirely clear. Recent studies have indicated that ischemia-reperfusion injury to the liver may be a significant factor promoting tumor recurrence and metastasis in animal models. If this is also true in humans, the effects of the Pringle maneuver, which has been widely used in hepatectomy for the past century, should be examined. To date, there are no reported data or randomized controlled studies examining the relationship between use of the Pringle maneuver and local tumor recurrence. We hypothesize that the long-term prognosis of patients with liver cancer could be worsened by use of the Pringle maneuver due to an increase in the rate of tumor recurrence in the liver remnant. We designed a multicenter, prospective, randomized surgical trial to test this hypothesis.


At least 498 eligible patients from five participating centers will be enrolled and randomized into either the Pringle group or the non-Pringle group in a ratio of 1:1 using a permuted-blocks randomization protocol. After the completion of surgical intervention, patients will be included in a 3-year follow-up program.


This multicenter surgical trial will examine whether the Pringle maneuver has a negative effect on the long-term outcome of hepatocellular carcinoma patients. The trial will also provide information about prognostic differences, safety, advantages and disadvantages between Pringle and non-Pringle surgical procedures. Ultimately, the results will increase the available information about the effects of ischemia-reperfusion injury on tumor recurrence, which will be of immense benefit to general surgery.

Trial registration webcite NCT00725335

Hepatocellular carcinoma; Ischemia/reperfusion; Hepatectomy; Pringle maneuver