The role of ischaemia-reperfusion injury and liver regeneration in hepatic tumour recurrenceKey points
Marianna Maspero,
Sumeyye Yilmaz,
Beatrice Cazzaniga,
Roma Raj,
Khaled Ali,
Vincenzo Mazzaferro,
Andrea Schlegel
Affiliations
Marianna Maspero
Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA; General Surgery and Liver Transplantation Unit, IRCCS Istituto Tumori, Milan, Italy
Sumeyye Yilmaz
Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
Beatrice Cazzaniga
Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
Roma Raj
Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
Khaled Ali
Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
Vincenzo Mazzaferro
General Surgery and Liver Transplantation Unit, IRCCS Istituto Tumori, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Italy
Andrea Schlegel
Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Corresponding author. Address: Transplantation Center, Digestive Disease and Surgery Institute and Department of Immunology, Lerner Research Institute, Cleveland Clinic, Ohio, USA; Tel.: +1 216 339 0741.
Summary: The risk of cancer recurrence after liver surgery mainly depends on tumour biology, but preclinical and clinical evidence suggests that the degree of perioperative liver injury plays a role in creating a favourable microenvironment for tumour cell engraftment or proliferation of dormant micro-metastases. Understanding the contribution of perioperative liver injury to tumour recurrence is imperative, as these pathways are potentially actionable. In this review, we examine the key mechanisms of perioperative liver injury, which comprise mechanical handling and surgical stress, ischaemia-reperfusion injury, and parenchymal loss leading to liver regeneration. We explore how these processes can trigger downstream cascades leading to the activation of the immune system and the pro-inflammatory response, cellular proliferation, angiogenesis, anti-apoptotic signals, and release of circulating tumour cells. Finally, we discuss the novel therapies under investigation to decrease ischaemia-reperfusion injury and increase regeneration after liver surgery, including pharmaceutical agents, inflow modulation, and machine perfusion.
