Title: Randomised Controlled Trial of Pringle Manoeuvre versus Portal Vein Clamping in Patients undergoing Liver Resection for Colorectal Liver Metastasis – A Pilot Study
Funder: Department of Health (England)

Abstract: Background: The portal vein and the hepatic artery supply 75% and 25% of the liver’s blood supply respectively, with each vessel contributing 50% of the liver’s oxygen requirement. The Pringle manoeuvre is commonly used to prevent blood loss at the time of liver resection2. During clamping a deprivation of oxygenation at the cellular level occurs, which is worsened by the fact that surgery will remove some of the functioning volume of the liver. Research has shown that the true damage occurs when the “starved” cells are reperfused, resulting in ischaemia-reperfusion injury (IRI). Not clamping the hepatic artery allows a continued supply of energy substrates to the cells, potentially reducing the damage caused by IRI. A recent RCT compared these two techniques along with a different technique and found that portal vein clamping resulted in faster recovery of liver functions 1. The proposed pilot study will overcome some of the methodological weaknesses in the reference study whilst piloting the approach in the UK. Aims: The aim of the pilot study is to test the protocol for the main study. The primary aim of the main study is to demonstrate that portal vein clamping is superior to Pringle manoeuvre in reducing the rate of septic complications by 30 days post-resection for Colorectal Liver Metastasis (CRLM). We also hypothesise that portal vein clamping due to its inherent blood supply preserving nature will lead to faster recovery of liver functions and better regeneration of the remaining liver. Plan of investigation: We plan to conduct an external pilot study, using a prospective, parallel group RCT design in patients requiring liver resection for CRLM. Overall 80 patients will be recruited into the study with the first 5 patients per surgeon (20 in total) recruited to address the learning curve associated with the new procedure. The remaining 60 patients (30 per arm) will be randomly allocated to the Pringle manoeuvre or portal vein clamping alone. Following standard abdominal incision and liver assessment, vessel clamping will be conducted based on the randomisation allocation and resection of liver lesion(s) performed. Routine blood tests will be conducted over the first 7 days post-procedure to assess the function of remnant liver. Any intra-operative and post-operative complications will be recorded. Patients will be followed up for three months following the procedure, at which point a routine Computerised Tomography (CT) scan of the abdomen and Quality of Life (QoL) assessments will be conducted. Benefits to the patients: This main study has the potential to deliver a wide range of benefits to patients: 1. A reduction in septic complications should lead to faster recovery of liver functions, less need for antibiotics, shorter hospital stay, lower post-operative deaths and improved cancer outcomes. 2. Improved regeneration of remnant liver should reduce liver failure rates and hasten patient recovery. 3. Portal vein clamping technique could be applied to living donor liver surgery, thereby reducing complications. 4. Portal vein clamping also has the potential to be applied to liver resection surgery for other diseases. The pilot study will inform refinement of the protocol for the main study. Benefits to the NHS: The proposed pilot study will contribute to the development of an evidence base for liver resection surgery for CRLM using portal vein clamping. Evidence from the main study showing a benefit in the use of portal vein clamping is likely to be set out in quality standards and guidelines, both locally and nationally, resulting in this procedure being adopted in other liver surgery units. In the current economic climate within the NHS, this research has the potential to reduce costs and improve cancer outcomes.


Research activity codes: 6.4 SURGERY
Health categories: CANCER AND NEOPLASMS