BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact mo...BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.展开更多
BACKGROUND The most effective treatment for advanced cirrhosis and portal hypertension is liver transplantation(LT).However,splenomegaly and hypersplenism can persist even after LT in patients with massive splenomegal...BACKGROUND The most effective treatment for advanced cirrhosis and portal hypertension is liver transplantation(LT).However,splenomegaly and hypersplenism can persist even after LT in patients with massive splenomegaly.AIM To examine the feasibility of performing partial splenectomy during LT in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism.METHODS Between October 2015 and February 2019,762 orthotopic LTs were performed for patients with end-stage liver diseases in Tianjin First Center Hospital.Eighty-four cases had advanced cirrhosis combined with severe splenomegaly and hypersplenism.Among these patients,41 received partial splenectomy during LT(PSLT group),and 43 received only LT(LT group).Patient characteristics,intraoperative parameters,and postoperative outcomes were retrospectively analyzed and compared between the two groups.RESULTS The incidence of postoperative hypersplenism(2/41,4.8%)and recurrent ascites(1/41,2.4%)in the PSLT group was significantly lower than that in the LT group(22/43,51.2%;8/43,18.6%,respectively).Seventeen patients(17/43,39.5%)in the LT group required two-stage splenic embolization,and further splenectomy was required in 6 of them.The operation time and intraoperative blood loss in the PSLT group(8.6±1.3 h;640.8±347.3 mL)were relatively increased compared with the LT group(6.8±0.9 h;349.4±116.1 mL).The incidence of postoperative bleeding,pulmonary infection,thrombosis and splenic arterial steal syndrome in the PSLT group was not different to that in the LT group,respectively.CONCLUSION Simultaneous PSLT is an effective treatment and should be performed in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism to prevent postoperative persistent hypersplenism.展开更多
Simultaneous liver,pancreas-duodenum,and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancrea...Simultaneous liver,pancreas-duodenum,and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis,renal failure,and insulin dependent diabetes mellitus(IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus,mycophenolate mofetil,and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation,and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.展开更多
BACKGROUND： Donor shortage is the biggest obstacle in organ transplantation. Living donor liver transplantation（LDLT） has been considered as a valuable approach to shortening waiting time. The objectives of this st...BACKGROUND： Donor shortage is the biggest obstacle in organ transplantation. Living donor liver transplantation（LDLT） has been considered as a valuable approach to shortening waiting time. The objectives of this study were to investigate the feasibility of utilizing donors older than 50 years in LDLT and to evaluate the graft function and recipient survival.METHODS： All LDLT cases（n=159） were divided into the older（donor age ≥50 years, n=10） and younger（donor age 〈50 years,n=149） donor groups. Donor graft and recipient condition pre-,intra- and post-operation were compared between the two groups.In particular, graft functions and recipient survivals were analyzed.RESULTS： The median donor age was 58.5（52.5-60.0） years in the older donor group and 25.0（23.0-32.0） in the younger donor group. There was no significant difference in cold ischemic time, anhepatic phase and operation time between the older and younger donor groups（P〉0.05）. However, the volume of red blood cell transfused in operation was greater in the older donor group than in the younger donor group（1900 vs 1200 m L, P=0.023）. The 1-, 3- and 5-year graft survival rates were 90%, 80% and 80% for the older donor group, and 92%, 87% and 87% for the younger donor group, respectively（P=0.459）.The 1-, 3- and 5-year survival rates were 100%, 90% and 90% for recipients with older grafts, and 93%, 87% and 87% for those with younger grafts, respectively（P=0.811）.CONCLUSION： It is safe for a LDLT recipient to receive liver from donors older than 50 years, and there is no significant adverse effect on graft function and long-term patients’ survival.展开更多
BACKGROUND Patients with end-stage liver disease usually have varying degrees of malnutrition,and severe malnutrition may affect the prognosis of patients after liver transplantation(LT).However,there is no recommende...BACKGROUND Patients with end-stage liver disease usually have varying degrees of malnutrition,and severe malnutrition may affect the prognosis of patients after liver transplantation(LT).However,there is no recommended standard for the nutrition assessment of patients waiting for LT,and it is unknown whether malnutrition has an impact on the occurrence of postoperative complications.AIM The study aim was to investigate the value of the controlling nutritional status(CONUT)score and psoas muscle thickness per height(PMTH)in predicting prognosis in LT.METHODS We retrospectively analyzed the clinical data of 313 patients who underwent classic orthotopic LT from January 2016 to December 2018 in Tianjin First Central Hospital affiliated with Tianjin Medical University.The CONUT score is derived from the preoperative serum albumin and total cholesterol levels,and total lymphocyte count.Patients were divided into low(≤4),medium(5–8),and high(9–12)CONUT score groups perioperative characteristics,Clavien-Dindo grade III/IV/V postoperative complications,graft loss and infection,and cumulative postoperative survival in the three groups were compared 3 mo after LT.PMTH was calculated as the ratio of the transverse thickness of the psoas muscle in the umbilical plane to the height of the patient.The cutoff values of receiver operating characteristic curves were determined separately for men and women.The values were 14.1 cm/m2 for women and 17.9 cm/m2 for men.The patients were then divided into low and high PMTH groups by the cutoff values.The comparison of data between the two groups was the same as above.RESULTS Patients with medium and high CONUT scores had lower preoperative serum hemoglobin,more intraoperative red blood cell(RBC)transfusions,longer postoperative intensive care unit stay and hospital stays,higher 7 and 14 preoperative-day serum bilirubin levels,and a higher incidence of postoperative grade III/IV complications and infections than patients with low CONUT scores.Differences in the 3-mo cumulative survival among the three groups were not significant.Patients with a low PMTH had higher preoperative serum urea nitrogen,more intraoperative packed RBC and frozen plasma transfusions,longer times to postoperative ventilator extubation,higher incidence of total postoperative complications,and a lower 3-mo cumulative survival than those with a high PMTH.CONCLUSION A CONUT score≥5 and a low PMTH were both associated with poor prognosis in LT.The CONUT score had no predictive value for short-term patient survival after LT,but the PMTH was predictive of short-term patient survival after LT.展开更多
BACKGROUND Loss of graft function after liver transplantation(LT) inevitably requires liver retransplant. Retransplantation of the liver(Re LT) remains controversial because of inferior outcomes compared with the prim...BACKGROUND Loss of graft function after liver transplantation(LT) inevitably requires liver retransplant. Retransplantation of the liver(Re LT) remains controversial because of inferior outcomes compared with the primary orthotopic LT(OLT).Meanwhile, if accompanied by vascular complications such as arterial and portal vein(PV) stenosis or thrombosis, it will increase difficulties of surgery. We hereby introduce our center’s experience in Re LT through a complicated case of ReLT.CASE SUMMARY We report a patient who suffered from hepatitis B-associated cirrhosis and underwent LT in December 2012. Early postoperative recovery was uneventful.Four months after LT, the patient’s bilirubin increased significantly and he was diagnosed with an ischemic-type biliary lesion caused by hepatic artery occlusion. The patient underwent percutaneous transhepatic cholangial drainage and repeatedly replaced intrahepatic biliary drainage tube regularly for 5 years.The patient developed progressive deterioration of liver function and underwent liver re-transplant in January 2019. The operation was performed in a classic OLT manner without venous bypass. Both the hepatic artery and PV were occluded and could not be used for anastomosis. The donor PV was anastomosed with the recipient’s left renal vein. The donor hepatic artery was connected to the recipient’s abdominal aorta. The bile duct reconstruction was performed in an end-to-end manner. The postoperative process was very uneventful and the patient was discharged 1 mo after retransplantation.CONCLUSION With the development of surgical techniques, portal thrombosis and arterial occlusion are no longer contraindications for ReLT.展开更多
Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipie...Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival(RFS) in hepatocellular carcinoma(HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specifc for the frst 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefts for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)ranks as the sixth most common cancer and the third-leading cause of cancer-related deaths worldwide.The multidisciplinary tumor board(MDTB)has been recognized for improving out...BACKGROUND Hepatocellular carcinoma(HCC)ranks as the sixth most common cancer and the third-leading cause of cancer-related deaths worldwide.The multidisciplinary tumor board(MDTB)has been recognized for improving outcomes in cancer management,but its role in patients with HCC undergoing liver transplantation(LT)remains underexplored.AIM To evaluate the impact of an MDTB on survival outcomes in patients with HCC undergoing LT.METHODS We retrospectively analyzed 393 patients with HCC who underwent LT at our institution from October 2015 to October 2021.Patients were categorized into the MDTB and non-MDTB groups.We compared preoperative and postoperative characteristics,overall survival(OS),and disease-free survival(DFS)between the two groups.RESULTS Within the University of California,San Francisco(UCSF)criteria,no significant differences in OS and DFS were noted between the MDTB and non-MDTB groups.However,for patients who exceeded the UCSF criteria,the MDTB group exhibited a substantial improvement in both OS and DFS.The 1-year,3-year,and 5-year OS rates for the MDTB group in this subgroup were 88.68%,75.29%,and 61.78%,respectively,compared to 83.02%,64.07%,and 38.25%,respectively in the non-MDTB group.Similarly,DFS rates were 89.47%,71.35%,and 63.52%,respectively,vs 82.18%,53.78%,and 34.04%,respectively.CONCLUSION The MDTB approach was particularly beneficial for patients with HCC exceeding the UCSF criteria,significantly improving OS and DFS.These findings advocate for integrating MDTB into clinical practice for optimizing the management of high-risk patients with HCC undergoing LT.展开更多
基金Supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBJC00001the Key Discipline Special Project of Tianjin Municipal Health Commission,No.TJWJ2022XK016.
文摘BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.
基金National Natural Science Foundation of China,No.81870444Tianjin Natural Science Foundation,No.19JCQNJC10300Spring Bud Plan of Tianjin First Central Hospital,No.TFCHCL201801.
文摘BACKGROUND The most effective treatment for advanced cirrhosis and portal hypertension is liver transplantation(LT).However,splenomegaly and hypersplenism can persist even after LT in patients with massive splenomegaly.AIM To examine the feasibility of performing partial splenectomy during LT in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism.METHODS Between October 2015 and February 2019,762 orthotopic LTs were performed for patients with end-stage liver diseases in Tianjin First Center Hospital.Eighty-four cases had advanced cirrhosis combined with severe splenomegaly and hypersplenism.Among these patients,41 received partial splenectomy during LT(PSLT group),and 43 received only LT(LT group).Patient characteristics,intraoperative parameters,and postoperative outcomes were retrospectively analyzed and compared between the two groups.RESULTS The incidence of postoperative hypersplenism(2/41,4.8%)and recurrent ascites(1/41,2.4%)in the PSLT group was significantly lower than that in the LT group(22/43,51.2%;8/43,18.6%,respectively).Seventeen patients(17/43,39.5%)in the LT group required two-stage splenic embolization,and further splenectomy was required in 6 of them.The operation time and intraoperative blood loss in the PSLT group(8.6±1.3 h;640.8±347.3 mL)were relatively increased compared with the LT group(6.8±0.9 h;349.4±116.1 mL).The incidence of postoperative bleeding,pulmonary infection,thrombosis and splenic arterial steal syndrome in the PSLT group was not different to that in the LT group,respectively.CONCLUSION Simultaneous PSLT is an effective treatment and should be performed in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism to prevent postoperative persistent hypersplenism.
基金Supported by National Natural Science Foundation of China,No.81400680Tianjin Natural Science Foundation,No.17JCQNJC12800
文摘Simultaneous liver,pancreas-duodenum,and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis,renal failure,and insulin dependent diabetes mellitus(IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus,mycophenolate mofetil,and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation,and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.
基金supported by a grant from the 863 National High-Tech Research and Development Program of China:Establishing Integrated Organ Preserving and Recovering System In Vitro as well as Evaluating and Screening Criteria of DCD donors(2012AA021001)
文摘BACKGROUND： Donor shortage is the biggest obstacle in organ transplantation. Living donor liver transplantation（LDLT） has been considered as a valuable approach to shortening waiting time. The objectives of this study were to investigate the feasibility of utilizing donors older than 50 years in LDLT and to evaluate the graft function and recipient survival.METHODS： All LDLT cases（n=159） were divided into the older（donor age ≥50 years, n=10） and younger（donor age 〈50 years,n=149） donor groups. Donor graft and recipient condition pre-,intra- and post-operation were compared between the two groups.In particular, graft functions and recipient survivals were analyzed.RESULTS： The median donor age was 58.5（52.5-60.0） years in the older donor group and 25.0（23.0-32.0） in the younger donor group. There was no significant difference in cold ischemic time, anhepatic phase and operation time between the older and younger donor groups（P〉0.05）. However, the volume of red blood cell transfused in operation was greater in the older donor group than in the younger donor group（1900 vs 1200 m L, P=0.023）. The 1-, 3- and 5-year graft survival rates were 90%, 80% and 80% for the older donor group, and 92%, 87% and 87% for the younger donor group, respectively（P=0.459）.The 1-, 3- and 5-year survival rates were 100%, 90% and 90% for recipients with older grafts, and 93%, 87% and 87% for those with younger grafts, respectively（P=0.811）.CONCLUSION： It is safe for a LDLT recipient to receive liver from donors older than 50 years, and there is no significant adverse effect on graft function and long-term patients’ survival.
基金Nation Natural Science Foundation of China(General Program),No.81870444Natural Science Foundation of Tianjin,No.17JCQNJC12800.
文摘BACKGROUND Patients with end-stage liver disease usually have varying degrees of malnutrition,and severe malnutrition may affect the prognosis of patients after liver transplantation(LT).However,there is no recommended standard for the nutrition assessment of patients waiting for LT,and it is unknown whether malnutrition has an impact on the occurrence of postoperative complications.AIM The study aim was to investigate the value of the controlling nutritional status(CONUT)score and psoas muscle thickness per height(PMTH)in predicting prognosis in LT.METHODS We retrospectively analyzed the clinical data of 313 patients who underwent classic orthotopic LT from January 2016 to December 2018 in Tianjin First Central Hospital affiliated with Tianjin Medical University.The CONUT score is derived from the preoperative serum albumin and total cholesterol levels,and total lymphocyte count.Patients were divided into low(≤4),medium(5–8),and high(9–12)CONUT score groups perioperative characteristics,Clavien-Dindo grade III/IV/V postoperative complications,graft loss and infection,and cumulative postoperative survival in the three groups were compared 3 mo after LT.PMTH was calculated as the ratio of the transverse thickness of the psoas muscle in the umbilical plane to the height of the patient.The cutoff values of receiver operating characteristic curves were determined separately for men and women.The values were 14.1 cm/m2 for women and 17.9 cm/m2 for men.The patients were then divided into low and high PMTH groups by the cutoff values.The comparison of data between the two groups was the same as above.RESULTS Patients with medium and high CONUT scores had lower preoperative serum hemoglobin,more intraoperative red blood cell(RBC)transfusions,longer postoperative intensive care unit stay and hospital stays,higher 7 and 14 preoperative-day serum bilirubin levels,and a higher incidence of postoperative grade III/IV complications and infections than patients with low CONUT scores.Differences in the 3-mo cumulative survival among the three groups were not significant.Patients with a low PMTH had higher preoperative serum urea nitrogen,more intraoperative packed RBC and frozen plasma transfusions,longer times to postoperative ventilator extubation,higher incidence of total postoperative complications,and a lower 3-mo cumulative survival than those with a high PMTH.CONCLUSION A CONUT score≥5 and a low PMTH were both associated with poor prognosis in LT.The CONUT score had no predictive value for short-term patient survival after LT,but the PMTH was predictive of short-term patient survival after LT.
文摘BACKGROUND Loss of graft function after liver transplantation(LT) inevitably requires liver retransplant. Retransplantation of the liver(Re LT) remains controversial because of inferior outcomes compared with the primary orthotopic LT(OLT).Meanwhile, if accompanied by vascular complications such as arterial and portal vein(PV) stenosis or thrombosis, it will increase difficulties of surgery. We hereby introduce our center’s experience in Re LT through a complicated case of ReLT.CASE SUMMARY We report a patient who suffered from hepatitis B-associated cirrhosis and underwent LT in December 2012. Early postoperative recovery was uneventful.Four months after LT, the patient’s bilirubin increased significantly and he was diagnosed with an ischemic-type biliary lesion caused by hepatic artery occlusion. The patient underwent percutaneous transhepatic cholangial drainage and repeatedly replaced intrahepatic biliary drainage tube regularly for 5 years.The patient developed progressive deterioration of liver function and underwent liver re-transplant in January 2019. The operation was performed in a classic OLT manner without venous bypass. Both the hepatic artery and PV were occluded and could not be used for anastomosis. The donor PV was anastomosed with the recipient’s left renal vein. The donor hepatic artery was connected to the recipient’s abdominal aorta. The bile duct reconstruction was performed in an end-to-end manner. The postoperative process was very uneventful and the patient was discharged 1 mo after retransplantation.CONCLUSION With the development of surgical techniques, portal thrombosis and arterial occlusion are no longer contraindications for ReLT.
基金supported by grants from the National S&T Major Project (2017ZX10203205)Key Program,National Natural Science Foundation of China (81930016)Zhejiang Provincial Natural Science Foundation of China (LY21H160026)。
文摘Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival(RFS) in hepatocellular carcinoma(HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specifc for the frst 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefts for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.
基金Supported by Natural Science Foundation of Tianjin,No.21JCYBJC01140Key Project of Tianjin Science and Technology Bureau Applied Basic Research,No.23JCZDJC01200+1 种基金Key Project of Scientific Research Plan of Tianjin Municipal Education Commission,No.2023YXZD07Project of Tianjin Science and Technology Bureau Applied Basic Research,No.23JCYBJC01800.
文摘BACKGROUND Hepatocellular carcinoma(HCC)ranks as the sixth most common cancer and the third-leading cause of cancer-related deaths worldwide.The multidisciplinary tumor board(MDTB)has been recognized for improving outcomes in cancer management,but its role in patients with HCC undergoing liver transplantation(LT)remains underexplored.AIM To evaluate the impact of an MDTB on survival outcomes in patients with HCC undergoing LT.METHODS We retrospectively analyzed 393 patients with HCC who underwent LT at our institution from October 2015 to October 2021.Patients were categorized into the MDTB and non-MDTB groups.We compared preoperative and postoperative characteristics,overall survival(OS),and disease-free survival(DFS)between the two groups.RESULTS Within the University of California,San Francisco(UCSF)criteria,no significant differences in OS and DFS were noted between the MDTB and non-MDTB groups.However,for patients who exceeded the UCSF criteria,the MDTB group exhibited a substantial improvement in both OS and DFS.The 1-year,3-year,and 5-year OS rates for the MDTB group in this subgroup were 88.68%,75.29%,and 61.78%,respectively,compared to 83.02%,64.07%,and 38.25%,respectively in the non-MDTB group.Similarly,DFS rates were 89.47%,71.35%,and 63.52%,respectively,vs 82.18%,53.78%,and 34.04%,respectively.CONCLUSION The MDTB approach was particularly beneficial for patients with HCC exceeding the UCSF criteria,significantly improving OS and DFS.These findings advocate for integrating MDTB into clinical practice for optimizing the management of high-risk patients with HCC undergoing LT.
