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Open Access 01-12-2016 | Study protocol

Perioperative and long-term outcomes of liver resection for hepatitis B virus-related hepatocellular carcinoma without versus with hepatic inflow occlusion: study protocol for a prospective randomized controlled trial

Authors: Yinzhe Xu, Jiye Chen, Hongguang Wang, Hui Zheng, Dan Feng, Aiqun Zhang, Jianjun Leng, Weidong Duan, Zhanyu Yang, Mingyi Chen, Xianjie Shi, Shouwang Cai, Wenbin Ji, Kai Jiang, Wenzhi Zhang, Yongliang Chen, Wanqing Gu, Jiahong Dong, Shichun Lu

Published in: Trials | Issue 1/2016

Abstract

Background

The high prevalence of hepatitis B virus (HBV) imposes a huge burden of hepatocellular carcinoma (HCC) in Asia. Surgical resection remains an important therapeutic strategy for HCC. Hepatic inflow occlusion, known as the Pringle maneuver, is the most commonly used method of reducing blood loss during liver parenchymal transection. A major issue with this maneuver is ischemia-reperfusion injury to the remnant liver, and the hemodynamic disturbance it induces in the tumor-bearing liver raises an oncological concern. Given the technical advances in living donor liver transplantation, vascular occlusion in liver resection can be avoided in experienced hands. The aim of this study is to compare the perioperative and long-term outcomes of liver resection for HBV-related HCC without versus with hepatic inflow occlusion.

Methods/design

This study will include eligible patients with HBV-related HCC elected for liver resection. Fifty-seven patients will be enrolled in each randomization 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 5 years. Data will be statistically analyzed on an intention-to-treat basis.

Discussion

This prospective randomized controlled trial is designed to compare the perioperative and long-term outcomes of liver resection for HBV-related HCC without versus with vascular occlusion. The clinical implications of these outcomes may change current surgical practice and fill the oncological gaps therein.

Trial registration

Clinicaltrials.gov identifier NCT02563158. Registered on 28 September 2015.

Available only for authorised users

Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94(2):153–6.CrossRefPubMed

Chen W, Zheng R, Zhang S, Zhao P, Li G, Wu L, et al. The incidences and mortalities of major cancers in China, 2009. Chin J Cancer. 2013;32(3):106–12. doi:10.5732/cjc.013.10018.CrossRefPubMedPubMedCentral

Nguyen VT, Law MG, Dore GJ. Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden. J Viral Hepat. 2009;16(7):453–63. doi:10.1111/j.1365-2893.2009.01117.x.CrossRefPubMed

Merican I, Guan R, Amarapuka D, Alexander MJ, Chutaputti A, Chien RN, et al. Chronic hepatitis B virus infection in Asian countries. J Gastroenterol Hepatol. 2000;15(12):1356–61.CrossRefPubMed

European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908–43. doi:10.1016/j.jhep.2011.12.001.CrossRef

Jarnagin WR, Gonen M, Fong Y, DeMatteo RP, Ben-Porat L, Little S, et al. Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade. Ann Surg. 2002;236(4):397–407. doi:10.1097/01.SLA.0000029003.66466.B3.CrossRefPubMedPubMedCentral

Gurusamy KS, Sheth H, Kumar Y, Sharma D, Davidson BR. Methods of vascular occlusion for elective liver resections. Cochrane Database Syst Rev. 2009;1:CD007632. doi:10.1002/14651858.CD007632.

Weigand K, Brost S, Steinebrunner N, Büchler M, Schemmer P, Müller M. Ischemia/reperfusion injury in liver surgery and transplantation: pathophysiology. HPB Surg. 2012;2012:176723. doi:10.1155/2012/176723.CrossRefPubMedPubMedCentral

Zhang Y, Zhang H, Elizabeth A, Liu XQ. Epidemiology of hepatitis B and associated liver diseases in China. Chin Med Sci J. 2013;27(4):243–8.CrossRefPubMed

10.

Xuan SY, Xin YN, Chen H, Shi GJ, Sun Y, Zhang J. Study on the correlations between HBsAg and hepatitis C virus expression as well as fibrotic staging in hepatocellular carcinoma and pericarcinomatous tissues [in Chinese]. Zhonghua Liu Xing Bing Xue Za Zhi. 2006;27(2):157–60.PubMed

11.

Torzilli G, Makuuchi M, Inoue K, Takayama T, Sakamoto Y, Sugawara Y, et al. No-mortality liver resection for hepatocellular carcinoma in cirrhotic and noncirrhotic patients: is there a way? A prospective analysis of our approach. Arch Surg. 1999;134(9):984–92.CrossRefPubMed

12.

Isozaki H, Okajima K, Kobayashi M, Hara H, Akimoto H. Experimental study of liver injury after partial hepatectomy with intermittent or continuous hepatic vascular occlusion: differences in tolerance to ischemia between normal and cirrhotic livers. Eur Surg Res. 1995;27(5):313–22.CrossRefPubMed

13.

Sakon M, Nagano H, Nakamori S, Dono K, Umeshita K, Murakami T, et al. Intrahepatic recurrences of hepatocellular carcinoma after hepatectomy: analysis based on tumor hemodynamics. Arch Surg. 2002;137(1):94–9.CrossRefPubMed

14.

Xiaobin F, Zipei L, Shuguo Z, Jiahong D, Xiaowu L. The Pringle manoeuvre should be avoided in hepatectomy for cancer patients due to its side effects on tumor recurrence and worse prognosis. Med Hypotheses. 2009;72(4):398–401. doi:10.1016/j.mehy.2008.11.029.CrossRefPubMed

15.

Li KW, Wen TF, Yan LN, Li B, Zeng Y, Zhao JC, et al. Donor right hepatectomy in living donor liver transplantation: report of 143 cases. Hepatogastroenterology. 2010;57(102–103):1232–6.PubMed

16.

Wen TF, Chen ZY, Yan LN, Li B, Zeng Y, Zhao JC, et al. Measures for increasing the safety of donors in living donor liver transplantation using right lobe grafts. Hepatobiliary Pancreat Dis Int. 2007;6(6):590–5.PubMed

17.

Capussotti L, Muratore A, Ferrero A, Massucco P, Ribero D, Polastri R. Randomized clinical trial of liver resection with and without hepatic pedicle clamping. Br J Surg. 2006;93(6):685–9. doi:10.1002/bjs.5301.CrossRefPubMed

18.

Poon RT, Fan ST, Lo CM, Liu CL, Lam CM, Yuen WK, et al. Improving perioperative outcome expands the role of hepatectomy in management of benign and malignant hepatobiliary diseases: analysis of 1222 consecutive patients from a prospective database. Ann Surg. 2004;240(4):698–710.PubMedPubMedCentral

19.

Llovet JM, Fuster J. Bruix J; Barcelona-Clínic Liver Cancer Group. The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl. 2004;10(2 Suppl 1):S115–20. doi:10.1002/lt.20034.CrossRefPubMed

20.

Montedori A, Bonacini MI, Casazza G, Luchetta ML, Duca P, Cozzolino F, et al. Modified versus standard intention-to-treat reporting: are there differences in methodological quality, sponsorship, and findings in randomized trials? A cross-sectional study. Trials. 2011;12:58. doi:10.1186/1745-6215-12-58.CrossRefPubMedPubMedCentral

21.

Little RJ, D’Agostino R, Cohen ML, Dickersin K, Emerson SS, Farrar JT, et al. The prevention and treatment of missing data in clinical trials. N Engl J Med. 2012;367(14):1355–60. doi:10.1056/NEJMsr1203730.CrossRefPubMedPubMedCentral

22.

Schulz KF, Altman DG, Moher D, CONSORT Group. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol. 2010;63(8):834–40. doi:10.1016/j.jclinepi.2010.02.005.CrossRefPubMed

23.

Ge PL, Du SD, Mao YL. Advances in preoperative assessment of liver function. Hepatobiliary Pancreat Dis Int. 2014;13(4):361–70.CrossRefPubMed

24.

MoHotPsRo C. Diagnosis, management, and treatment of hepatocellular carcinoma (v2011) [in Chinese]. Lin Chuang Gan Dan Bing Za Zhi. 2011;16(10):1141–59.

25.

Smyrniotis V, Kostopanagiotou G, Theodoraki K, Tsantoulas D, Contis JC. The role of central venous pressure and type of vascular control in blood loss during major liver resections. Am J Surg. 2004;187(3):398–402. doi:10.1016/j.amjsurg.2003.12.001.CrossRefPubMed

26.

Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011;149(5):713–24. doi:10.1016/j.surg.2010.10.001.CrossRefPubMed

27.

Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250(2):187–96. doi:10.1097/SLA.0b013e3181b13ca2.CrossRefPubMed

28.

Fu SY, Lau WY, Li GG, Tang QH, Li AJ, Pan ZY, et al. A prospective randomized controlled trial to compare Pringle maneuver, hemihepatic vascular inflow occlusion, and main portal vein inflow occlusion in partial hepatectomy. Am J Surg. 2011;201(1):62–9. doi:10.1016/j.amjsurg.2009.09.029.CrossRefPubMed

29.

Ni JS, Lau WY, Yang Y, Pan ZY, Wang ZG, Liu H, et al. A prospective randomized controlled trial to compare Pringle manoeuvre with hemi-hepatic vascular inflow occlusion in liver resection for hepatocellular carcinoma with cirrhosis. J Gastrointest Surg. 2013;17(8):1414–21. doi:10.1007/s11605-013-2236-z.CrossRefPubMed

30.

World Health Organization (WHO). Prevention and control of viral hepatitis infection: framework for global action. Geneva: WHO; 2012. http://www.who.int/hiv/pub/hepatitis/Framework/en/. Accessed 2 October 2016.

31.

Chen CL, Kabiling CS, Concejero AM. Why does living donor liver transplantation flourish in Asia? Nat Rev Gastroenterol Hepatol. 2013;10(12):746–51. doi:10.1038/nrgastro.2013.194.CrossRefPubMed

32.

Han KH, Kudo M, Ye SL, Choi JY, Poon RT, Seong J, et al. Asian consensus workshop report: expert consensus guideline for the management of intermediate and advanced hepatocellular carcinoma in Asia. Oncology. 2011;81 Suppl 1:158–64. doi:10.1159/000333280.CrossRefPubMed

33.

Simillis C, Li T, Vaughan J, Becker LA, Davidson BR, Gurusamy KS. A Cochrane systematic review and network meta-analysis comparing treatment strategies aiming to decrease blood loss during liver resection. Int J Surg. 2015;23(Pt A):128–36. doi:10.1016/j.ijsu.2015.09.064.CrossRefPubMed

34.

Lau WY, Lai EC, Lau SH. Methods of vascular control technique during liver resection: a comprehensive review. Hepatobiliary Pancreat Dis Int. 2010;9(5):473–81.PubMed

35.

Huang J, Tang W, Hernandez-Alejandro R, Bertens KA, Wu H, Liao M, et al. Intermittent hepatic inflow occlusion during partial hepatectomy for hepatocellular carcinoma does not shorten overall survival or increase the likelihood of tumor recurrence. Medicine. 2014;93(28):e288. doi:10.1097/MD.0000000000000288.CrossRefPubMedPubMedCentral

36.

Xiaobin F, Shuguo Z, Jian Z, Yudong Q, Lijian L, Kuansheng M, et al. Effect of the Pringle maneuver on tumor recurrence of hepatocellular carcinoma after curative resection (EPTRH): a randomized, prospective, controlled multicenter trial. BMC Cancer. 2012;12:340. doi:10.1186/1471-2407-12-340.CrossRefPubMedPubMedCentral

37.

Balzan S, Belghiti J, Farges O, Ogata S, Sauvanet A, Delefosse D, et al. The “50-50 criteria” on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy. Ann Surg. 2005;242(6):824–9.CrossRefPubMedPubMedCentral

38.

Lentsch AB, Kato A, Yoshidome H, McMasters KM, Edwards MJ. Inflammatory mechanisms and therapeutic strategies for warm hepatic ischemia/reperfusion injury. Hepatology. 2000;32(2):169–73. doi:10.1053/jhep.2000.9323.CrossRefPubMed

39.

Koch M, Garden OJ, Padbury R, Rahbari NN, Adam R, Capussotti L, et al. Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery. Surgery. 2011;149(5):680–8. doi:10.1016/j.surg.2010.12.002.CrossRefPubMed

40.

Rahbari NN, Garden OJ, Padbury R, Maddern G, Koch M, Hugh TJ, et al. Post-hepatectomy haemorrhage: a definition and grading by the International Study Group of Liver Surgery (ISGLS). HPB (Oxford). 2011;13(8):528–35. doi:10.1111/j.1477-2574.2011.00319.x.CrossRef

Title: Perioperative and long-term outcomes of liver resection for hepatitis B virus-related hepatocellular carcinoma without versus with hepatic inflow occlusion: study protocol for a prospective randomized controlled trial
Authors: Yinzhe Xu
Jiye Chen
Hongguang Wang
Hui Zheng
Dan Feng
Aiqun Zhang
Jianjun Leng
Weidong Duan
Zhanyu Yang
Mingyi Chen
Xianjie Shi
Shouwang Cai
Wenbin Ji
Kai Jiang
Wenzhi Zhang
Yongliang Chen
Wanqing Gu
Jiahong Dong
Shichun Lu
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Trials / Issue 1/2016
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-016-1621-9

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Perioperative and long-term outcomes of liver resection for hepatitis B virus-related hepatocellular carcinoma without versus with hepatic inflow occlusion: study protocol for a prospective randomized controlled trial

Abstract

Background

Methods/design

Discussion

Trial registration

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods/design

Discussion

Trial registration

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