BACKGROUND: Split liver transplantation increases the number of grafts available for transplantation. Pre-recovery assessment of liver graft volume is essential for selecting suitable recipients. The purpose of this ...BACKGROUND: Split liver transplantation increases the number of grafts available for transplantation. Pre-recovery assessment of liver graft volume is essential for selecting suitable recipients. The purpose of this study was to determine the ability and feasibility of constructing a 3-D model to aid in surgical planning and to predict graft weight prior to an in situ division of the donor liver. METHODS: Over 11 months, 3-D volumetric reconstruction of 4 deceased donors was performed using Pathfinder Scout liver volumetric software. Demographic, laboratory, operative, perioperative and survival data for these patients along with donor demographic data were collected prospectively and analyzed retrospectively. RESULTS: The average predicted weight of the grafts from the adult donors obtained from an in situ split procedure were 1130 g (930-1458 g) for the extended right lobe donors and 312 g (222-396 g) for left lateral segment grafts. Actual adult graft weight was 92% of the predicted weight for both the extended right grafts and the left lateral segment grafts. The predicted and actual graft weights for the pediatric donors were 176 g and 210 g for the left lateral segment grafts and 308 g and 280 g for the extended right lobe grafts,respectively. All grafts were transplanted except for the right lobe from the pediatric donors due to the small graft weight.CONCLUSIONS: On-site volumetric assessment of donors provides useful information for the planning of an in situ split and for selection of recipients. This information may expand the donor pool to recipients previously felt to be unsuitable due to donor and/or recipient weight.展开更多
Progressive familial intrahepatic cholestasis(PFIC) is a constellation of inherited disorders that result in the impairment of bile flow through the liver that predominantly affects children. The accumulation of bile ...Progressive familial intrahepatic cholestasis(PFIC) is a constellation of inherited disorders that result in the impairment of bile flow through the liver that predominantly affects children. The accumulation of bile results in progressive liver damage, and if left untreated leads to end stage liver disease and death. Patients often present with worsening jaundice and pruritis within the first few years of life. Many of these patients will progress to end stage liver disease and require liver transplantation. The role and timing of liver transplantation still remains debated especially in the management of PFIC1. In those patients who are appropriately selected, liver transplantation offers an excellent survival benefit. Appropriate timing and selection of patients for liver transplantation will be discussed, and the short and long term management of patients post liver transplantation will also be described.展开更多
Obesity is on the rise worldwide. As a result, unprecedented rates of patients are presenting with end stage liver disease in the setting of non-alcoholic fatty liver disease(NAFLD) and are requiring liver transplanta...Obesity is on the rise worldwide. As a result, unprecedented rates of patients are presenting with end stage liver disease in the setting of non-alcoholic fatty liver disease(NAFLD) and are requiring liver transplantation. There are significant concerns that the risk factors associated with obesity and the metabolic syndrome might have a detrimental effect on the long term outcomes following liver transplantation. In general, short term patient and graft outcomes for both obese and morbidly obese patients are comparable with that of non-obese patients, however, several studies report an increase in peri-operative morbidity and increased length of stay. Continued studies documenting the long-term outcomes from liver transplantation are needed to further examine the risk of recurrent disease(NAFLD) and also further define the role risk factors such cardiovascular disease might play long term. Effective weight reduction in the post liver transplant setting may mitigate the risks associated with the metabolic syndrome long-term.展开更多
Objective:Patient-derived xenograft(PDX)models provide a promising preclinical platform for hepatocellular carcinoma(HCC).However,the molecular features associated with successful engraftment of PDX models have not be...Objective:Patient-derived xenograft(PDX)models provide a promising preclinical platform for hepatocellular carcinoma(HCC).However,the molecular features associated with successful engraftment of PDX models have not been revealed.Methods:HCC tumor samples from 76 patients were implanted in immunodeficient mice.The molecular expression was evaluated by immunohistochemistry.Patient and tumor characteristics as well as tumor molecular expressions were compared for PDX engraftment using the Chi-square test.The independent prediction parameters were identified by logistic regression analyses.Results:The engraftment rate for PDX models from patients with HCC was 39.47%(30/76).Tumors from younger patients and patients with elevated preoperative alpha-fetoprotein level had higher engraftment rates.Tumors with poor differentiation and vascular invasion were related to engraftment success.The positive expression of CK19,CD133,glypican-3(GPC3),and Ki67 in tumor samples was associated with engraftment success.Logistic regression analyses indicated that GPC3 and Ki67 were two of the strongest predictors of PDX engraftment.Tumors with GPC3/Ki67 phenotypes showed heterogeneous engraftment rates,with 71.9%in GPC3^(+)/Ki67^(+)tumors,30.8%in GPC3^(-)/Ki67^(+)tumors,15.0%in GPC3^(+)/Ki67^(-)tumors,and 0 in GPC3^(-)/Ki67^(-)tumors.Conclusions:Successful engraftment of HCC PDXs was significantly related to molecular features.Tumors with the GPC3+/Ki67+phenotype were the most likely to successfully establish HCC PDXs.展开更多
1 MAIN TEXT Patient-derived xenograft(PDX)models have garnered increasing attention since the last decade.These models are typically characterized by the implantation of fresh patient-derived tumor tissues into immuno...1 MAIN TEXT Patient-derived xenograft(PDX)models have garnered increasing attention since the last decade.These models are typically characterized by the implantation of fresh patient-derived tumor tissues into immunodeficient mice.PDX models are well recognized in academic laboratories,pharmaceutical institutions,and specialized commercial organizations as having the ability to recapitulate genomics,transcriptomics,proteomics,and metabolomics of the parental tumor tissue[1,2].Recently,these models have been successfully used in preclinical studies to identify potential biomarkers for drug response and resistance,and to measure tumor evolution in response to treatment[3,4].Favorable outcomes demonstrated using PDX models could be used as ideal models for preclinical research and clinical translation studies.展开更多
文摘BACKGROUND: Split liver transplantation increases the number of grafts available for transplantation. Pre-recovery assessment of liver graft volume is essential for selecting suitable recipients. The purpose of this study was to determine the ability and feasibility of constructing a 3-D model to aid in surgical planning and to predict graft weight prior to an in situ division of the donor liver. METHODS: Over 11 months, 3-D volumetric reconstruction of 4 deceased donors was performed using Pathfinder Scout liver volumetric software. Demographic, laboratory, operative, perioperative and survival data for these patients along with donor demographic data were collected prospectively and analyzed retrospectively. RESULTS: The average predicted weight of the grafts from the adult donors obtained from an in situ split procedure were 1130 g (930-1458 g) for the extended right lobe donors and 312 g (222-396 g) for left lateral segment grafts. Actual adult graft weight was 92% of the predicted weight for both the extended right grafts and the left lateral segment grafts. The predicted and actual graft weights for the pediatric donors were 176 g and 210 g for the left lateral segment grafts and 308 g and 280 g for the extended right lobe grafts,respectively. All grafts were transplanted except for the right lobe from the pediatric donors due to the small graft weight.CONCLUSIONS: On-site volumetric assessment of donors provides useful information for the planning of an in situ split and for selection of recipients. This information may expand the donor pool to recipients previously felt to be unsuitable due to donor and/or recipient weight.
文摘Progressive familial intrahepatic cholestasis(PFIC) is a constellation of inherited disorders that result in the impairment of bile flow through the liver that predominantly affects children. The accumulation of bile results in progressive liver damage, and if left untreated leads to end stage liver disease and death. Patients often present with worsening jaundice and pruritis within the first few years of life. Many of these patients will progress to end stage liver disease and require liver transplantation. The role and timing of liver transplantation still remains debated especially in the management of PFIC1. In those patients who are appropriately selected, liver transplantation offers an excellent survival benefit. Appropriate timing and selection of patients for liver transplantation will be discussed, and the short and long term management of patients post liver transplantation will also be described.
文摘Obesity is on the rise worldwide. As a result, unprecedented rates of patients are presenting with end stage liver disease in the setting of non-alcoholic fatty liver disease(NAFLD) and are requiring liver transplantation. There are significant concerns that the risk factors associated with obesity and the metabolic syndrome might have a detrimental effect on the long term outcomes following liver transplantation. In general, short term patient and graft outcomes for both obese and morbidly obese patients are comparable with that of non-obese patients, however, several studies report an increase in peri-operative morbidity and increased length of stay. Continued studies documenting the long-term outcomes from liver transplantation are needed to further examine the risk of recurrent disease(NAFLD) and also further define the role risk factors such cardiovascular disease might play long term. Effective weight reduction in the post liver transplant setting may mitigate the risks associated with the metabolic syndrome long-term.
基金supported by grants from the National Science and Technology Major Project of China(No.2017ZX10203205)the National Natural Science Funds for Distinguished Young Scholar of China(No.81625003)+1 种基金Key Program National Natural Science Foundation of China(No.81930016)Key Research&Development Plan of Zhejiang Province(No.2019C03050)。
文摘Objective:Patient-derived xenograft(PDX)models provide a promising preclinical platform for hepatocellular carcinoma(HCC).However,the molecular features associated with successful engraftment of PDX models have not been revealed.Methods:HCC tumor samples from 76 patients were implanted in immunodeficient mice.The molecular expression was evaluated by immunohistochemistry.Patient and tumor characteristics as well as tumor molecular expressions were compared for PDX engraftment using the Chi-square test.The independent prediction parameters were identified by logistic regression analyses.Results:The engraftment rate for PDX models from patients with HCC was 39.47%(30/76).Tumors from younger patients and patients with elevated preoperative alpha-fetoprotein level had higher engraftment rates.Tumors with poor differentiation and vascular invasion were related to engraftment success.The positive expression of CK19,CD133,glypican-3(GPC3),and Ki67 in tumor samples was associated with engraftment success.Logistic regression analyses indicated that GPC3 and Ki67 were two of the strongest predictors of PDX engraftment.Tumors with GPC3/Ki67 phenotypes showed heterogeneous engraftment rates,with 71.9%in GPC3^(+)/Ki67^(+)tumors,30.8%in GPC3^(-)/Ki67^(+)tumors,15.0%in GPC3^(+)/Ki67^(-)tumors,and 0 in GPC3^(-)/Ki67^(-)tumors.Conclusions:Successful engraftment of HCC PDXs was significantly related to molecular features.Tumors with the GPC3+/Ki67+phenotype were the most likely to successfully establish HCC PDXs.
基金This work was funded by grants from the National Science and Technology Major Project of China(2017ZX10203205)the National Natural Science Funds for Distinguished Young Scholar of China(81625003)+1 种基金the Key Research&Development Plan of Zhejiang Province(2019C03050)the National Natural Science Foundation of China(81702858).
文摘1 MAIN TEXT Patient-derived xenograft(PDX)models have garnered increasing attention since the last decade.These models are typically characterized by the implantation of fresh patient-derived tumor tissues into immunodeficient mice.PDX models are well recognized in academic laboratories,pharmaceutical institutions,and specialized commercial organizations as having the ability to recapitulate genomics,transcriptomics,proteomics,and metabolomics of the parental tumor tissue[1,2].Recently,these models have been successfully used in preclinical studies to identify potential biomarkers for drug response and resistance,and to measure tumor evolution in response to treatment[3,4].Favorable outcomes demonstrated using PDX models could be used as ideal models for preclinical research and clinical translation studies.