Transplantation represents the most effective treatment for end-stage liver diseases but is limited by the shortage of healthy donor organs.Extended criteria donor(ECD)liver grafts are increasingly utilized in clinica...Transplantation represents the most effective treatment for end-stage liver diseases but is limited by the shortage of healthy donor organs.Extended criteria donor(ECD)liver grafts are increasingly utilized in clinical practice to mitigate this challenge.However,impaired ischemic tolerance of these grafts jeopardizes organ viability during cold storage.Machine perfusion(MP)was designed to improve organ preservation and reduce posttransplant complications.Nevertheless,it is increasingly evident that MP alone may not preserve ECD grafts optimally.Increasing emphasis has thus been placed on modified MP strategies,including the use of different perfusates,modified perfusion modalities,and different therapeutic interventions.Here,we introduce a novel term,"MP Plus,"denoting these additional strategies that are designed to restore organ function and potentially enable regeneration of ECD grafts.In this review,we summarize the existing and potential modified MP strategies and discuss their advantages in reconditioning different ECD grafts in clinical settings.展开更多
The liver is the commonest site of metastatic disease for patients with colorectal cancer,with at least 25%developing colorectal liver metastases(CRLM)during the course of their illness.The management of CRLM has evol...The liver is the commonest site of metastatic disease for patients with colorectal cancer,with at least 25%developing colorectal liver metastases(CRLM)during the course of their illness.The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology(cross sectional,nuclear medicine and interventional),Oncology,Liver surgery,Colorectal surgery,and Histopathology.Patient management is based on assessment of sophisticated clinical,radiological and biomarker information.Despite incomplete evidence in this very heterogeneous patient group,maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure.To this end,liver resection is maximised by the use of downsizing chemotherapy,optimisation of liver remnant by portal vein embolization,associating liver partition and portal vein ligation for staged hepatectomy,and combining resection with ablation,in the context of improvements in the functional assessment of the future remnant liver.Liver resection may safely be carried out laparoscopically or open,and synchronously with,or before,colorectal surgery in selected patients.For unresectable patients,treatment options including systemic chemotherapy,targeted biological agents,intraarterial infusion or bead delivered chemotherapy,tumour ablation,stereotactic radiotherapy,and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability.Currently evolving areas include biomarker characterisation of tumours,the development of novel systemic agents targeting specific oncogenic pathways,and the potential reemergence of radical surgical options such as liver transplantation.展开更多
The liver has remarkable regenerative potential,with the capacity to regenerate after 75%hepatectomy in humans and up to 90%hepatectomy in some rodent models,enabling it to meet the challenge of diverse injury types,i...The liver has remarkable regenerative potential,with the capacity to regenerate after 75%hepatectomy in humans and up to 90%hepatectomy in some rodent models,enabling it to meet the challenge of diverse injury types,including physical trauma,infection,inflammatory processes,direct toxicity,and immunological insults.Current understanding of liver regeneration is based largely on animal research,historically in large animals,and more recently in rodents and zebrafish,which provide powerful genetic manipulation experimental tools.Whilst immensely valuable,these models have limitations in extrapolation to the human situation.In vitro models have evolved from 2-dimensional culture to complex 3 dimensional organoids,but also have shortcomings in replicating the complex hepatic micro-anatomical and physiological milieu.The process of liver regeneration is only partially understood and characterized by layers of complexity.Liver regeneration is triggered and controlled by a multitude of mitogens acting in autocrine,paracrine,and endocrine ways,with much redundancy and cross-talk between biochemical pathways.The regenerative response is variable,involving both hypertrophy and true proliferative hyperplasia,which is itself variable,including both cellular phenotypic fidelity and cellular trans-differentiation,according to the type of injury.Complex interactions occur between parenchymal and non-parenchymal cells,and regeneration is affected by the status of the liver parenchyma,with differences between healthy and diseased liver.Finally,the process of termination of liver regeneration is even less well understood than its triggers.The complexity of liver regeneration biology combined with limited understanding has restricted specific clinical interventions to enhance liver regeneration.Moreover,manipulating the fundamental biochemical pathways involved would require cautious assessment,for fear of unintended consequences.Nevertheless,current knowledge provides guiding principles for strategies to optimise liver regeneration potential.展开更多
基金the National Key Research and Development Program of China(2021YFA1100500)the Zhejiang University-Cambridge Global Partnership Fund+2 种基金the National Natural Science Foundation of China(81930016 and 82003248)the Key Research and Development Program of Zhejiang Province(2022C03108)the Projects of Medical and Health Technology Program in Zhejiang Province(WKJZJ-2120).
文摘Transplantation represents the most effective treatment for end-stage liver diseases but is limited by the shortage of healthy donor organs.Extended criteria donor(ECD)liver grafts are increasingly utilized in clinical practice to mitigate this challenge.However,impaired ischemic tolerance of these grafts jeopardizes organ viability during cold storage.Machine perfusion(MP)was designed to improve organ preservation and reduce posttransplant complications.Nevertheless,it is increasingly evident that MP alone may not preserve ECD grafts optimally.Increasing emphasis has thus been placed on modified MP strategies,including the use of different perfusates,modified perfusion modalities,and different therapeutic interventions.Here,we introduce a novel term,"MP Plus,"denoting these additional strategies that are designed to restore organ function and potentially enable regeneration of ECD grafts.In this review,we summarize the existing and potential modified MP strategies and discuss their advantages in reconditioning different ECD grafts in clinical settings.
文摘The liver is the commonest site of metastatic disease for patients with colorectal cancer,with at least 25%developing colorectal liver metastases(CRLM)during the course of their illness.The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology(cross sectional,nuclear medicine and interventional),Oncology,Liver surgery,Colorectal surgery,and Histopathology.Patient management is based on assessment of sophisticated clinical,radiological and biomarker information.Despite incomplete evidence in this very heterogeneous patient group,maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure.To this end,liver resection is maximised by the use of downsizing chemotherapy,optimisation of liver remnant by portal vein embolization,associating liver partition and portal vein ligation for staged hepatectomy,and combining resection with ablation,in the context of improvements in the functional assessment of the future remnant liver.Liver resection may safely be carried out laparoscopically or open,and synchronously with,or before,colorectal surgery in selected patients.For unresectable patients,treatment options including systemic chemotherapy,targeted biological agents,intraarterial infusion or bead delivered chemotherapy,tumour ablation,stereotactic radiotherapy,and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability.Currently evolving areas include biomarker characterisation of tumours,the development of novel systemic agents targeting specific oncogenic pathways,and the potential reemergence of radical surgical options such as liver transplantation.
文摘The liver has remarkable regenerative potential,with the capacity to regenerate after 75%hepatectomy in humans and up to 90%hepatectomy in some rodent models,enabling it to meet the challenge of diverse injury types,including physical trauma,infection,inflammatory processes,direct toxicity,and immunological insults.Current understanding of liver regeneration is based largely on animal research,historically in large animals,and more recently in rodents and zebrafish,which provide powerful genetic manipulation experimental tools.Whilst immensely valuable,these models have limitations in extrapolation to the human situation.In vitro models have evolved from 2-dimensional culture to complex 3 dimensional organoids,but also have shortcomings in replicating the complex hepatic micro-anatomical and physiological milieu.The process of liver regeneration is only partially understood and characterized by layers of complexity.Liver regeneration is triggered and controlled by a multitude of mitogens acting in autocrine,paracrine,and endocrine ways,with much redundancy and cross-talk between biochemical pathways.The regenerative response is variable,involving both hypertrophy and true proliferative hyperplasia,which is itself variable,including both cellular phenotypic fidelity and cellular trans-differentiation,according to the type of injury.Complex interactions occur between parenchymal and non-parenchymal cells,and regeneration is affected by the status of the liver parenchyma,with differences between healthy and diseased liver.Finally,the process of termination of liver regeneration is even less well understood than its triggers.The complexity of liver regeneration biology combined with limited understanding has restricted specific clinical interventions to enhance liver regeneration.Moreover,manipulating the fundamental biochemical pathways involved would require cautious assessment,for fear of unintended consequences.Nevertheless,current knowledge provides guiding principles for strategies to optimise liver regeneration potential.
