Study of Liver Resection With Versus Without Hepatic Inflow Occlusion for the HBV-related HCC (OHx-NOHx)

Short- and Long-term Outcomes of Liver Resection With Versus Without Hepatic Inflow Occlusion for the Hepatitis B Virus-related Hepatocellular Carcinoma: a Prospective Randomized Controlled Trial

The study aims to compare the perioperative and long-term outcomes of liver resection for HBV-related HCC with versus without hepatic inflow occlusion.

Study Overview

• Status: Unknown
• Conditions: Surgery; Liver Cancer
• Intervention / Treatment: Procedure: non-occlusion technique

Detailed Description

High prevalence of hepatitis B virus (HBV) imposes a huge burden of hepatocellular carcinoma (HCC) in Asia. Liver resection remains the mainstay of treatment for HCC. Hepatic inflow occlusion, known as the Pringle maneuver, is most commonly used to reduce blood loss during liver parenchymal transection. A major issue about this maneuver is the ischemia-reperfusion injury to the remnant liver. And the hemodynamic disturbance to the tumor-bearing liver remains an oncologic concern. Given the technical advances in living donor liver transplantation, vascular occlusion can be avoided in liver resection by experienced hands. This study aims to compare the perioperative and long-term outcomes of liver resection for HBV-related HCC without versus with hepatic inflow occlusion.

This study will include eligible patients with HBV-related HCC elected for liver resection. 57 patients will be enrolled in each randomized 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 five years. Data will be statistically analyzed on an intention-to-treat basis.

This prospective randomized controlled trial is designed to evaluate the feasibility of liver resections for HBV-related HCC without vascular occlusion. Clinical implication of its outcomes may change the present surgical practice and fill the oncologic gaps therein.

• Study Type: Interventional
• Enrollment (Anticipated): 114
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Chinese PLA General Hospital
      • Contact: Yinzhe Xu, M.D., Ph.D.; Phone Number: 86-10-66936609; Email: james_hbp@163.com
      • Principal Investigator: Shichun Lu, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Elective liver resection due to HBV-related HCC with Barcelona-Clinic Liver Cancer (BCLC) staging 0 or A;
2. Child-Pugh classified A with or without cirrhosis, or reversed to A from B after conventional therapy;
3. Tumors located either in the left or right hemiliver;
4. Resection extent was a hemi-hepatectomy or less;
5. Informed consent.

Exclusion Criteria:

1. Having comorbidity that contraindicates surgery;
2. Participation in concurrent interventional trials with interference to this study;
3. Eligible for laparoscopic hepatectomy;
4. Requiring concomitant procedures, such as digestive, vascular or biliary reconstruction;
5. Lack of compliance for treatment or future follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Hx with hepatic inflow occlusion; Hepatectomy is carried out using Pringle maneuver in cycles of 15 minutes clamping + 5 minutes unclamping of the hepatoduodenal ligament.
Experimental: Hx with non-occlusion technique; Hepatectomy without hepatic inflow occlusion (non-occlusion technique)	Procedure: non-occlusion technique; Hepatectomy is carried out without hepatic inflow control. (non-occlusion technique); Other Names: hepatectomy without hepatic inflow occlusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum total bilirubin on postoperative day 5	Postoperative liver insufficiency characterized by the serum total bilirubin on POD 5.	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative blood loss	Total blood loss from the incision to the closure of abdomen	Entire operation duration
Requirement of blood transfusion	The amount of intraoperative blood transfusion	Entire operation duration
Operative time	The time from induction of anesthesia to the closure of abdomen	Entire operation duration
Postoperative intensive-care unit (ICU) stay	Duration of stay in ICU	Duration of stay in ICU
Hospital stay	Duration of hospital stay	Duration of hospital stay
Total hospital expenditure	Total costs during hospital stay	Duration of hospital stay
Perioperative systemic inflammatory response	Perioperative systemic inflammatory response is characterized by elevated serum level of tumor necrosis factor-α (TNF-α), interleukins (IL)-1α, 2, 6, 8 and 10, procalcitonin (PCT) and C-reactive protein (CRP) at different time points.	an expected average of 7 days
Postoperative morbi-mortality	Postoperative morbi-mortality is characterized by postoperative complication and its severity based on Clavien-Dindo classification and in-hospital mortality	an expected average of 12 days in hospital
Long-term oncologic outcomes	1, 3, 5-year tumor recurrence rate	5 years after operation
Long-term survival	1, 3, 5-year overall survival (OS) and disease (tumor)-free survival (DFS)	5 years after operation

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Investigators: Principal Investigator: Shichun Lu, MD, PhD, Department of Hepatobiliary Surgery, Chinese PLA General Hospital, 28 Fuxing Road, Haidian, Beijing, 100853, China

Publications and helpful links

General Publications

• Llovet JM, Fuster J, Bruix J; Barcelona-Clinic Liver Cancer Group. The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl. 2004 Feb;10(2 Suppl 1):S115-20. doi: 10.1002/lt.20034.
• Katz SC, Shia J, Liau KH, Gonen M, Ruo L, Jarnagin WR, Fong Y, D'Angelica MI, Blumgart LH, Dematteo RP. Operative blood loss independently predicts recurrence and survival after resection of hepatocellular carcinoma. Ann Surg. 2009 Apr;249(4):617-23. doi: 10.1097/SLA.0b013e31819ed22f.
• Dong JH, Yang SZ, Duan WD, Ji WB, Cai SW, Wang J, Shi XJ, Jiang K, Xia HT, He L, Zhang WZ, Huang XQ, Huang ZQ. [Clinical application of precise liver resection techniques in patients with complicated liver space-occupying lesions]. Zhonghua Wai Ke Za Zhi. 2009 Nov 1;47(21):1610-5. Chinese.
• Huang ZQ, Xu LN, Yang T, Zhang WZ, Huang XQ, Liu R, Cai SW, Zhang AQ, Feng YQ, Zhou NX, Dong JH. [Liver resection: single center experiences of 2008 consecutive resections in 20 years]. Zhonghua Wai Ke Za Zhi. 2008 Sep 1;46(17):1314-21. Chinese.
• Dong J, Yang S, Zeng J, Cai S, Ji W, Duan W, Zhang A, Ren W, Xu Y, Tan J, Bu X, Zhang N, Wang X, Wang X, Meng X, Jiang K, Gu W, Huang Z. Precision in liver surgery. Semin Liver Dis. 2013 Aug;33(3):189-203. doi: 10.1055/s-0033-1351781. Epub 2013 Aug 13. Danish, English.
• Sugiyama Y, Ishizaki Y, Imamura H, Sugo H, Yoshimoto J, Kawasaki S. Effects of intermittent Pringle's manoeuvre on cirrhotic compared with normal liver. Br J Surg. 2010 Jul;97(7):1062-9. doi: 10.1002/bjs.7039.
• Kim YI, Song KE, Ryeon HK, Hwang YJ, Yun YK, Lee JW, Chun BY. Enhanced inflammatory cytokine production at ischemia/reperfusion in human liver resection. Hepatogastroenterology. 2002 Jul-Aug;49(46):1077-82.
• Fu SY, Lau WY, Li GG, Tang QH, Li AJ, Pan ZY, Huang G, Yin L, Wu MC, Lai EC, Zhou WP. 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 Jan;201(1):62-9. doi: 10.1016/j.amjsurg.2009.09.029. Epub 2010 Apr 20. Erratum In: Am J Surg. 2011 Jul;202(1):117. multiple author names corrected.
• Xu Y, Chen J, Wang H, Zheng H, Feng D, Zhang A, Leng J, Duan W, Yang Z, Chen M, Shi X, Cai S, Ji W, Jiang K, Zhang W, Chen Y, Gu W, Dong J, Lu S. 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. Trials. 2016 Oct 11;17(1):492. doi: 10.1186/s13063-016-1621-9.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): January 1, 2019
• Study Completion (Anticipated): January 1, 2019

Study Registration Dates

• First Submitted: September 26, 2015
• First Submitted That Met QC Criteria: September 28, 2015
• First Posted (Estimate): September 30, 2015

Study Record Updates

• Last Update Posted (Estimate): May 12, 2016
• Last Update Submitted That Met QC Criteria: May 10, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: randomized controlled trial; inflammatory response; ischemia-reperfusion injury; liver resection; blood inflow control
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: JFJZYY-GD-15-01; NO. 2012BAI06B01 (Other Grant/Funding Number: National Key Technology R&D Program of China); NO. 2012ZX10002-017 (Other Grant/Funding Number: National S&T Major Project for Infectious Diseases of China)