Prospective study of change in liver function and fat in patients with colorectal liver metastases undergoing preoperative chemotherapy: protocol for the CLiFF Study

Kat L Parmar, Derek O'Reilly, Juan W Valle, Michael Braun, Jo H Naish, Steve R Williams, William K Lloyd, Lee Malcomson, Katharine Cresswell, Colin Bamford, Andrew G Renehan, Kat L Parmar, Derek O'Reilly, Juan W Valle, Michael Braun, Jo H Naish, Steve R Williams, William K Lloyd, Lee Malcomson, Katharine Cresswell, Colin Bamford, Andrew G Renehan

Abstract

Introduction: Preoperative chemotherapy in patients undergoing resection for colorectal liver metastases (CLM) improves oncological outcomes. However, chemotherapy-associated liver injury (occurring in two patterns: vascular and fat deposition) is a real clinical concern prior to hepatic resection. After major liver resection, regeneration of the residual liver is a prerequisite for recovery and avoidance of liver failure, but this regenerative capacity may be hindered by chemotherapy. Thus, there is a need to predict for this serious complication. Over the past two decades, several tests and derived indices have been developed, which have failed to achieve clinical utility, mainly as they were indirect measurements of liver function. Here, we will use a novel test of liver function (the liver maximum capacity (LiMAx) test), and measure liver fat using MRI.

Methods and analysis: This prospective study will assess changes in liver function longitudinally, measured by the LiMAx test, and liver fat, measured by advanced MRI using both MR spectroscopy and the modified Dixon method, in up to 35 patients undergoing preoperative chemotherapy for CLM. The primary outcomes will be the changes in liver function and fat compared with baseline prechemotherapy measurements. Secondary outcome measures include: routinely measured liver function blood tests, anthropometric measurements, postoperative histology and digital quantification of fat, postoperative complications and mortality and quality of life.

Ethics and dissemination: The study was approved by a National Health Service Research Ethics Committee and registered with the Health Research Authority. Dissemination will be via international and national conferences and the National Institute for Health Research network. Manuscripts will be published.

Trial registration number: This study is registered online at www.clinicaltrials.gov (registration number NCT03562234).

Keywords: chemotherapy; colorectal surgery; hepatobiliary surgery.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
Direct acyclic graph.
Figure 2
Figure 2
Study participant timeline. LiMAx, liver maximum capacity.

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