Xiaobin et al. BMC Cancer 2012, 12:340 http://www.biomedcentral.com/1471-2407/12/340 marker tests, liver function tests, chest x-ray, and ultrasound examination. In addition, enhanced CT scans of thorax and abdomen will be performed at 3, 6, 12, 18, 24, 32, and36 months postoperatively. Add- itional investigations including 18 F-fluorodexyglucose positron emission tomography scan, magnetic reson- ance imaging, or digital subtraction angiography will be scheduled as required to investigate possible tumor recurrence. At each visit, a follow-up evaluation form will be completed. If tumor recurs, the patient will be hospitalized and treated according to the clinical situation. Data management and monitoring The Institute of Hepatobiliary Surgery of Southwest Hospital is responsible for the coordination of this trial. The clinical and laboratory data of all patients will be centrally collected and entered in a password-protected database at the Clinical Trial Center of Southwest Hos- pital, Third Military Medical University. All samples and clinical data will be tracked using a unique research tracking number. The link between research tracking numbers and patient identifiers will be kept in a limited- access database on a computer. Trial data quality reports will be generated routinely to evaluate missing data and inconsistencies. Accrual rates and follow-up will be monitored periodically throughout the study period. If a potential problem is identified, it will be brought to the attention of the investigator for discussion and treat- ment. All operation records will be reviewed to ensure that the study protocol was followed. Monitoring of data and patient safety will be per- formed according to good clinical practice GCP guide- lines by an independent Data and Safety Monitoring Board (DSMB) established by the Chinese PLA General Hospital. The DSMB will meet approximately twice a year to monitor safety and to advise the centers about study progress. In addition, the Clinical Trial Center will provide data to the DSMB Chair at regular intervals, and at his or her request, to ensure early identification of any major adverse outcomes of treatment. The DSMB will monitor adverse effects and respond to variations in the data, and is responsible for recommending whether the study should continue, whether the protocol should be modified, or whether there should be early termination. Duration of the trial, and current trial status The trial is planned to last a total of 5 years, consisting of: protocol development (6 months), training (3 months), main recruitment (9 months), follow-up (36 months), and analysis (6 months). All the team members have com- pleted their training. The expected end date of this trial will be July, 2013. Page 6 of 8 Discussion Even though short-term outcomes of the Pringle maneu- ver have been investigated, its effects on tumor recur- rence and metastasis have not been discussed. This trial will focus on the effects of the I/R injury caused by the Pringle maneuver on the long-term prognosis of primary HCC patients with HBV infection. Previous experimental studies have demonstrated that tumor recurrence could be increased by I/R injury to the liver remnant, and that the tumor cell might become more aggressive [33,35]. If this occurs in the clinical set- ting, use of the Pringle maneuver must be re-evaluated, because it has been widely performed in the past to avoid massive blood loss during hepatic resection. The Pringle maneuver may cause additional I/R injury be- sides that caused by the hepatic resection itself, which will affect tumor cells and the liver remnant. With advances in surgical techniques and periopera- tive management, portal triad clamping is not necessary for every hepatectomy, and it may be important to fur- ther discuss its use. We hypothesize that the prognosis of patients with primary HCC might be worsened by use of the Pringle maneuver during hepatectomy. If this is true, this routine surgical technique should be revised or even avoided during hepatectomy, especially in HCC patients. We all know that it can take time for theories based on animal experiments to have an effect on clin- ical practice. In some cases, the final outcome may be affected by multiple clinical factors. For this trial, reported data indicate that these factors mainly include the hepatitis virus DNA load, surgical margins, micro- vascular thrombosis, tumor size, number of tumor nodules, microvascular invasion, tumor capsule forma- tion, blood loss, and blood transfusion. We take all these factors into account in our inclusion and exclusion cri- teria and subgroup analysis. Whatever the results of this randomized controlled trial, we will gain important in- formation about the long-term effects of the Pringle maneuver. Competing interests All the authors declare that they have no competing interests. Authors’ contributions FX, ZS, BP, and DJ designed the study. ZJ, QY, LL, MK, LX, XF, and WS will oversee the enrollment of patients and the ongoing study protocols. YD will perform the data analysis. All authors read and approved the final manuscript. Acknowledgments This study is supported by the National Major Science and Technology Project of China on the prevention and treatment of infectious diseases, for human immunodeficiency virus and HBV (2008ZX10002-026). Author details 1Institute of hepatobiliary surgery, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China. 2Institute of hepatobiliary surgery, Chinese PLA General Hospital, Beijing, P. R. China. 3Institute of liver cancer,