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
AIM To perform a systematic review and meta-analysis on minimally vs conventional invasive techniques for harvesting grafts for living donor liver transplantation. METHODS PubMed, Web of Science, EMBASE, and the Cochr...AIM To perform a systematic review and meta-analysis on minimally vs conventional invasive techniques for harvesting grafts for living donor liver transplantation. METHODS PubMed, Web of Science, EMBASE, and the Cochrane Library were searched comprehensively for studies comparing MILDH with conventional living donor hepatectomy (CLDH). Intraoperative and postoperative outcomes (operative time, estimated blood loss, postoperative liver function, length of hospital stay, analgesia use, complications, and survival rate) were analyzed in donors and recipients. Articles were included if they: (1) compared the outcomes of MILDH and CLDH; and (2) reported at least some of the above outcomes. RESULTS Of 937 articles identified, 13, containing 1592 patients, met our inclusion criteria and were included in the meta-analysis. For donors, operative time [weighted mean difference (WMD) = 20.68, 95% CI: -6.25-47.60, p = 0.13] and blood loss (WMD = -32.61, 95% CI: -80.44-5.21, p = 0.18) were comparable in the two groups. In contrast, analgesia use (WMD = -7.79, 95% CI: -14.06-1.87, p = 0.01), postoperative complications [odds ratio (OR) = 0.62, 95% CI: 0.44-0.89, p = 0.009], and length of hospital stay (WMD): -1.25, 95% CI: -2.35-0.14, p = 0.03) significantly favored MILDH. No differences were observed in recipient outcomes, including postoperative complications (OR = 0.93, 95% CI: 0.66-1.31, p = 0.68) and survival rate (hr = 0.96, 95% CI: 0.27-3.47, p = 0.95). Funnel plot and statistical methods showed a low probability of publication bias. CONCLUSION MILDH is safe, effective, and feasible for living donor liver resection with fewer donor postoperative complications, reduced length of hospital stay and analgesia requirement than CLDH.展开更多
Biliary stenosis is a common complication after liver transplantation,and has an incidence rate ranging from4.7%to 12.5%based on our previous study.Three types of biliary stenosis(anastomotic stenosis,nonanastomotic p...Biliary stenosis is a common complication after liver transplantation,and has an incidence rate ranging from4.7%to 12.5%based on our previous study.Three types of biliary stenosis(anastomotic stenosis,nonanastomotic peripheral stenosis and non-anastomotic central hilar stenosis)have been identified.We report the outcome of two patients with anastomotic stricture after liver transplantation who underwent successfulcutting balloon treatment.Case 1 was a 40-year-old male transplanted due to subacute fulminant hepatitis C.Case 2 was a 57-year-old male transplanted due to hepatitis B virus-related end-stage cirrhosis associated with hepatocellular carcinoma.Both patients had similar clinical scenarios:refractory anastomotic stenosis after orthotopic liver transplantation and failure of balloon dilation of the common bile duct to alleviate biliary stricture.展开更多
To the Editor:Despite dramatic improvements in the prognosis of pediatric liver transplantation(LT),postoperative complications are still a leading cause of death in grafts and patients.Child recipients were shown to ...To the Editor:Despite dramatic improvements in the prognosis of pediatric liver transplantation(LT),postoperative complications are still a leading cause of death in grafts and patients.Child recipients were shown to have a higher risk of thrombotic complications than in adult recipients,due to differences in etiology,narrowed hepatic vessels due to hypoplasia,more meticulous surgical techniques,and other factors.[1]Thrombotic complications include hepatic artery thrombosis(HAT).展开更多
Metabolic disease,including diabetes mellitus,hypertension,dyslipidemia,obesity,and hyperuricemia,is a common complication after liver transplantation and a risk factor for cardiovascular disease and death.The develop...Metabolic disease,including diabetes mellitus,hypertension,dyslipidemia,obesity,and hyperuricemia,is a common complication after liver transplantation and a risk factor for cardiovascular disease and death.The development of metabolic disease is closely related to the side effects of immunosuppressants.Therefore,optimization of the immunosuppressive regimen is very important for the prevention and treatment of metabolic disease.The Chinese Society of Organ Transplantation has developed an expert consensus on the management of metabolic diseases in Chinese liver transplant recipients based on recent studies.Emphasis is placed on the risk factors of metabolic diseases,the effect of immunosuppressants on metabolic disease,and the prevention and treatment of metabolic diseases.展开更多
BACKGROUND: With the expansion of surgical criteria, the comparative efficacy between surgical resection (SR) and liver transplantation (LT) for hepatocellular carcinoma is inconclusive. This study aimed to develop a ...BACKGROUND: With the expansion of surgical criteria, the comparative efficacy between surgical resection (SR) and liver transplantation (LT) for hepatocellular carcinoma is inconclusive. This study aimed to develop a prognostic nomogram for predicting recurrence-free survival of hepatocellular carcinoma patients after resection and explored the possibility of using nomogram as treatment algorithm reference. METHODS: From 2003 to 2012, 310 hepatocellular carcinoma patients within Hangzhou criteria undergoing resection or liver transplantation were included. Total tumor volume, albumin level, HBV DNA copies and portal hypertension were included for constructing the nomogram. The resection patients were stratified into low- and high-risk groups by the median nomogram score of 116. Independent risk factors were identified and a visually orientated nomogram was constructed using a Cox proportional hazards model to predict the recurrence risk for SR patients. RESULTS: The low-risk SR group had better outcomes compared with the high-risk SR group (3-year recurrence-free survival rate, 71.1% vs 35.9%; 3-year overall survival rate, 89.8% vs 78.9%, both P<0.001). The high-risk SR group was associated with a worse recurrence-free survival rate but similar overall survival rate compared with the transplantation group (3-year recurrence-free survival rate, 35.9% vs 74.1%, P<0.001; 3-year overall survival rate, 78.9% vs 79.6%, P>0.05). CONCLUSIONS: This nomogram offers individualized recurrence risk evaluation for hepatocellular carcinoma patients within Hangzhou criteria receiving resection. Transplantation should be considered the first-line treatment for high risk patients.展开更多
Liver transplantation(LT)is the only effective treatment for hepatopulmonary syndrome(HPS).Moreover,perioperative refractory hypoxemia(pRH)is a prevalent life-threatening condition and has extremely limited treatment ...Liver transplantation(LT)is the only effective treatment for hepatopulmonary syndrome(HPS).Moreover,perioperative refractory hypoxemia(pRH)is a prevalent life-threatening condition and has extremely limited treatment options.Here,we report three patients with HPS who experienced pRH after LT and were consecutively treated with different salvage therapies,ephedrine inhalation,intravenous use of methylene blue with nitric oxide(NO)inhalation,and NO inhalation alone.The results showed that unresolved severe hypoxia may induce fatal morbidity such as early biliary leakage and acute kidney injury.Early initiation of NO inhalation,rather than ephedrine,can significantly improve oxygenation in patients with pRH and may help prevent hypoxia-related complications.Therefore,based on the response to these exploratory salvage treatments,we further demonstrate the unique ventilation-perfusion mismatch pathophysiology in specific lung regions during pRH in HPS.We propose that early inhalation of NO is an important treatment option to rescue severe hypoxia in patients with HPS during the perioperative period of LT.展开更多
AIM To perform a meta-analysis on laparoscopic hepatectomy VS conventional liver resection for treating hepatolithiasis.METHODS We conducted a systematic literature search on Pub Med,Embase,Web of Science and Cochrane...AIM To perform a meta-analysis on laparoscopic hepatectomy VS conventional liver resection for treating hepatolithiasis.METHODS We conducted a systematic literature search on Pub Med,Embase,Web of Science and Cochrane Library,and undertook a meta-analysis to compare the efficacy and safety of laparoscopic hepatectomy V S conventional open liver resection for local hepatolithiasis in the left or right lobe. Intraoperative and postoperative outcomes(time,estimated blood loss,blood transfusion rate,postoperative intestinal function recovery time,length of hospital stay,postoperative complication rate,initial residual stone,final residual stone and stone recurrence) were analyzed systematically.RESULTS A comprehensive literature search retrieved 16 publications with a total of 1329 cases. Meta-analysis of these studies showed that the laparoscopic approach for hepatolithiasis was associated with significantly less intraoperative estimated blood loss [weighted mean difference(WMD): 61.56,95% confidence interval(CI): 14.91-108.20,P = 0.01],lower blood transfusion rate [odds ratio(OR): 0.41,95%CI: 0.22-0.79,P = 0.008],shorter intestinal function recovery time(WMD: 0.98,95%CI: 0.47-1.48,P = 0.01),lower total postoperative complication rate(OR: 0.52,95%CI: 0.39-0.70,P < 0.0001) and shorter stay in hospital(WMD: 3.32,95%CI: 2.32-4.32,P < 0.00001). In addition,our results showed no significant differences between the two groups in operative time(WMD: 21.49,95%CI: 0.27-43.24,P = 0.05),residual stones(OR: 0.79,95%CI: 0.50-1.25,P = 0.31) and stone recurrence(OR: 0.34,95%CI: 0.11-1.08,P = 0.07). Furthermore,with subgroups analysis,our results proved that the laparoscopic approach for hepatolithiasis in the left lateral lobe and left side could achieve satisfactory therapeutic effects. CONCLUSION The laparoscopic approach is safe and effective,with less intraoperative estimated blood loss,fewer postoperative complications,reduced length of hospital stay and shorter intestinal function recovery time than with conventional approaches.展开更多
The disease burden related to hepatocellular carcinoma(HCC) is increasing. Most HCC patients are diagnosed at the advanced stage and multikinase inhibitors have been the only treatment choice for them. Recently, the a...The disease burden related to hepatocellular carcinoma(HCC) is increasing. Most HCC patients are diagnosed at the advanced stage and multikinase inhibitors have been the only treatment choice for them. Recently, the approval of immune checkpoint inhibitors(ICIs) has provided a new therapeutic strategy for HCC. It is noteworthy that the positive outcomes of the phase Ⅲ clinical trial IMBrave150 [atezolizumab(anti-programmed cell death ligand 1 antibody) combined with bevacizumab(anti-vascular endothelial growth factor monoclonal antibody)],showed that overall survival and progression-free survival were significantly better with sorafenib. This combination therapy has become the new standard therapy for advanced HCC and has also attracted more attention in the treatment of HCC with anti-angiogenesis-immune combination therapy. Currently, the synergistic antitumor efficacy of this combination has been shown in many preclinical and clinical studies. In this review, we discuss the mechanism and clinical application of anti-angiogenics and immunotherapy in HCC, outline the relevant mechanism and rationality of the combined application of antiangiogenics and ICIs, and point out the existing challenges of the combination therapy.展开更多
Acute-on-chronic liver failure(ACLF)can be cured by liver transplantation;however,perioperative complications still affect posttransplant outcomes.In recent years,early rehabilitation for critical illness,liver diseas...Acute-on-chronic liver failure(ACLF)can be cured by liver transplantation;however,perioperative complications still affect posttransplant outcomes.In recent years,early rehabilitation for critical illness,liver disease,and surgery have significantly improved organ reserve function,surgery tolerance,and postoperative quality of life.They could also be applied in the perioperative period of liver transplantation in patients with ACLF.Therefore,the Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association,the Organ Transplant Committee of China Association Rehabilitation Medicine,and the Guangdong Medical Doctor Association of Organ Transplantation conducted a comprehensive review of rehabilitation in end-stage liver disease,critical illness and surgical patients by summarizing current evidence and best clinical practices and proposed a practice consensus on evaluation of cardiopulmonary and physical function,rehabilitation or physiotherapies,as well as the safety concerns in perioperative liver transplant recipients.It will be a valuable resource for hepatologists,transplant surgeons,and intensivists as they care for ACLF patients during transplantation.展开更多
Lenvatinib,a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer,facing limitations due to drug resistance.Here,we applied a multidimensiona...Lenvatinib,a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer,facing limitations due to drug resistance.Here,we applied a multidimensional,high-throughput screening platform comprising patient-derived resistant liver tumor cells(PDCs),organoids(PDOs),and xenografts(PDXs)to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings.Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment,expediting drug repurposing screens.Pharmacological screening identified romidepsin,YM155,apitolisib,NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models.Notably,romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway.A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models.Collectively,our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer,providing a feasible multidimensional platform for personalized medicine.展开更多
Background:The downstaging of hepatocellular carcinoma(HCC)has been confirmed to benefit liver transplantation(LT)patients whose tumors are beyond the transplantation criteria.Milan criteria(MC),a tumor size and numbe...Background:The downstaging of hepatocellular carcinoma(HCC)has been confirmed to benefit liver transplantation(LT)patients whose tumors are beyond the transplantation criteria.Milan criteria(MC),a tumor size and number-based assessment,is currently used as the endpoint in these patients.However,many studies believe that tumor biological behavior should be added to the evaluation criteria for downstaging efficacy.Hence,this study aimed to explore the feasibility of Hangzhou criteria(HC),which introduced tumor grading and alpha-fetoprotein in addition to tumor size and number,as an endpoint of downstaging.Methods:We performed a multicenter and retrospective study of 206 patients accepted locoregional therapy(LRT)as downstaging/bridge treatment prior to LT in three centers of China.Results:Recipients were divided into four groups:failed downstaging to the HC(group A,n=46),successful downstaging to the HC(group B,n=30),remained within the HC all the time(group C,n=113),and tumor progressed(group D,n=17).The 3-year HCC recurrence probabilities of groups B and C were not significantly different(10.3%vs.11.6%,P=0.87).The HCC recurrent rate was significantly higher in group A(52.3%)compared with that in group B/C(P<0.05).Seven patients(7/76,9.2%)whose tumor exceeded the the HC were successfully downstaged to the MC,and 39.5%(30/76)to the the HC.In group B,23 patients remained beyond the MC and their survivals were as well as those of patients within the MC.Conclusions:Compared to the MC,HC downstaging criteria can give more HCC patients access to LT and furthermore,the outcome of these patients is the same as those matching MC downstaging criteria.Hangzhou downstaging criteria therefore is applicable in clinical practice.展开更多
Indocyanine green(ICG)is a fluorescent dye that is widely used in hepatobiliary surgery for fluorescence contrast.ICG is selectively absorbed by the liver after intravenous injection and then secreted into the bile.IC...Indocyanine green(ICG)is a fluorescent dye that is widely used in hepatobiliary surgery for fluorescence contrast.ICG is selectively absorbed by the liver after intravenous injection and then secreted into the bile.ICG's unique catabolism and fluorescence characteristics allow for multiple applications in liver transplantation.We have divided the applications of ICG fluorescence imaging in liver transplantation into:(i)cholangiography,(ii)evaluation of liver transplantation vessels,(iii)liver mapping,and(iv)evaluation of donor liver quality.In this review,we summarize the current status of applications of ICG fluorescence imaging in liver transplantation.展开更多
Pancreatic neuroendocrine neoplasms(pNENs)are highly heterogeneous,and the management of pNENs patients can be intractable.To address this challenge,an expert committee was established on behalf of the Chinese Pancrea...Pancreatic neuroendocrine neoplasms(pNENs)are highly heterogeneous,and the management of pNENs patients can be intractable.To address this challenge,an expert committee was established on behalf of the Chinese Pancreatic Surgery Association,which consisted of surgical oncologists,gastroenterologists,medical oncologists,endocrinologists,radiologists,pathologists,and nuclear medicine specialists.By reviewing the important issues regarding the diagnosis and treatment of pNENs,the committee concluded evidence-based statements and recommendations in this article,in order to further improve the management of pNENs patients in China.展开更多
Patients with recurrent hepatocellular carcinoma(HCC)following liver transplantation(LT)have a poor prognosis owing to rapid tumor progression.Yttrium-90 radioembolization(^(90)Y-RE)has been shown to be a safe and eff...Patients with recurrent hepatocellular carcinoma(HCC)following liver transplantation(LT)have a poor prognosis owing to rapid tumor progression.Yttrium-90 radioembolization(^(90)Y-RE)has been shown to be a safe and efficacious transarterial radioembolization treatment for patients with advanced HCC.However,to our knowledge,no data are available for patients with recurrent HCC following LT.Here we report a case of severe bile duct complication after transarterial radioembolization with yttrium-90 in a patient who experienced HCC recurrence following LT.The present case suggests that ^(90)Y-RE should be cautiously performed in patients with recurrent HCC following LT.展开更多
Background and aim:Coronavirus disease 2019(COVID-19)is a life-threatening disease that predomi-nantly causes respiratory failure.The impact of COVID-19 on other organs remains elusive.Herein,we aimed to investigate t...Background and aim:Coronavirus disease 2019(COVID-19)is a life-threatening disease that predomi-nantly causes respiratory failure.The impact of COVID-19 on other organs remains elusive.Herein,we aimed to investigate the effects of COVID-19 on the hepatobiliary system.Methods:In the current study,we obtained the clinical records and laboratory results from 66 laboratory-confirmed patients with COVID-19 at the Wuhan Tongji Hospital between 10 February 2020 and 28 February 2020.The detailed clinical features and laboratory findings were collected for analysis.Bioinformatics analysis was conducted to evaluate the correlation between gamma-glutamyl transferase(GGT)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry receptor angiotensin-converting enzyme 2(ACE2).Results:In this cohort,30(51.7%)patients had abnormal liver function on admission,which was asso-ciated with disease severity and enriched in the male and diabetic patients.The elevated levels of direct bilirubin(P¼0.029)and GGT(P¼0.004)were common in patients with severe pneumonia when compared with those with mild pneumonia.In addition,elevated levels of GGT(P¼0.003)and aspartate aminotransferase(AST)(P¼0.007)were positively associated with longer hospital stay.The expression of ACE2 was closely associated with GGT in various human tissues because they shared the common transcriptional regulator hepatic nuclear factor-1 b(HNF1B).Conclusions:Increased GGT levels were common in severe cases and elevated GGT levels were positively associated with prolonged hospital stay and disease severity.Due to the consistent expression with ACE2,GGT is a potent biomarker indicating the susceptibility of SARS-CoV-2 infection.展开更多
Background:Abnormal expression of long non-coding RNAs(lncRNAs)has been found in almost all tumors in humans,providing numerous potential diagnostic and prognostic biomarkers,and therapeutic targets.Materials and meth...Background:Abnormal expression of long non-coding RNAs(lncRNAs)has been found in almost all tumors in humans,providing numerous potential diagnostic and prognostic biomarkers,and therapeutic targets.Materials and methods:The Cancer Genome Atlas(TCGA)database was used to screen potential LncRNAs,and 30 paired hepatocellular carcinoma(HCC)tissues were used to investigate RP11-307C12.11 expression levels by qRT-PCR and another 105 HCC tissues by in situ hybridizsation(ISH).RP11-307C12.11 overexpression and knockdown experiments were performed to investigate the effects of RP11-307C12.11 on HCC growth through in vitro and in vivo assays(MTT assay,colony formation assay,EdU assay,and xenograft model).The molecular mechanism underlying these effects was confirmed by MS2-RIP-assay,RIP assay,luciferase assay,and rescue experiments.Results:RP11-307C12.11 expression level was significantly higher in tumor tissues than in the adjacent normal tissues.Elevated RP11-307C12.11 expression level was associated with poor prognosis of HCC patients,and it may be represented as an independent prognostic biomarker in patients with HCC.Functionally,RP11-307C12.11 overexpression promoted HCC growth both in vitro and in vivo;however,its knockdown reversed these effects.Mechanistically,we found that RP11-307C12.11 expressed predominantly in the cytoplasm and sponged microRNA(miR)-138 to regulate its common target CCND1 and PDK1.Conclusions:Thus,we found that RP11-307C12.11 acts as an oncogene in HCC by binding to miR-138,which might provide a novel target for HCC therapy.展开更多
Advances in the field of stem cells have led to the development of a technology called organoids.Organoids are cell cluster structures formed by the cultivation of stem cells in a three-dimensional environment in vitr...Advances in the field of stem cells have led to the development of a technology called organoids.Organoids are cell cluster structures formed by the cultivation of stem cells in a three-dimensional environment in vitro,and they can simulate the living environment of cells in vivo.Organoids play an important role in the screening of drugs for tumor therapy.Compared with traditional drug screening models,tumor organoid models derived from patient tumors have higher sensitivity,heterogeneity,and stability and can restore the real situation of tumors more effectively.Researchers have conducted a number of researches on the feasibility of using organoid technology in drug screening.By testing and comparing the effects of antitumor drugs in organoids and primary tumors,we can select the most appropriate treatment drugs for patients.In the past ten years,organoids from dozens of tissues and biological sample banks from several main organs have been established,and a large number of anticancer drugs have been screened out.This article summarizes the advantages and disadvantages of traditional drug screening models,discusses the development history of organoid technology,and reviews the research results on organoids from tumor drug screening.In addition,the combination of organoid technology and other modern biotechnologies is put forward to further promote the role of organoid technology in the medical field.Finally,this article reviews the history,progress,and prospect on organoids from the view of antitumor drug screening.展开更多
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Science and Technology Planning Project of Guangzhou,No.201604020001
文摘AIM To perform a systematic review and meta-analysis on minimally vs conventional invasive techniques for harvesting grafts for living donor liver transplantation. METHODS PubMed, Web of Science, EMBASE, and the Cochrane Library were searched comprehensively for studies comparing MILDH with conventional living donor hepatectomy (CLDH). Intraoperative and postoperative outcomes (operative time, estimated blood loss, postoperative liver function, length of hospital stay, analgesia use, complications, and survival rate) were analyzed in donors and recipients. Articles were included if they: (1) compared the outcomes of MILDH and CLDH; and (2) reported at least some of the above outcomes. RESULTS Of 937 articles identified, 13, containing 1592 patients, met our inclusion criteria and were included in the meta-analysis. For donors, operative time [weighted mean difference (WMD) = 20.68, 95% CI: -6.25-47.60, p = 0.13] and blood loss (WMD = -32.61, 95% CI: -80.44-5.21, p = 0.18) were comparable in the two groups. In contrast, analgesia use (WMD = -7.79, 95% CI: -14.06-1.87, p = 0.01), postoperative complications [odds ratio (OR) = 0.62, 95% CI: 0.44-0.89, p = 0.009], and length of hospital stay (WMD): -1.25, 95% CI: -2.35-0.14, p = 0.03) significantly favored MILDH. No differences were observed in recipient outcomes, including postoperative complications (OR = 0.93, 95% CI: 0.66-1.31, p = 0.68) and survival rate (hr = 0.96, 95% CI: 0.27-3.47, p = 0.95). Funnel plot and statistical methods showed a low probability of publication bias. CONCLUSION MILDH is safe, effective, and feasible for living donor liver resection with fewer donor postoperative complications, reduced length of hospital stay and analgesia requirement than CLDH.
基金Key Scientific and Technological Projects of Guangdong Province,No.2014B020228003,No.2014B030301041 and No.2015B020226004the Natural Science Foundation of Guangdong Province,No.2015A030312013the Science and Technology Planning Project of Guangzhou,No.201400000001-3 and No.158100076
文摘Biliary stenosis is a common complication after liver transplantation,and has an incidence rate ranging from4.7%to 12.5%based on our previous study.Three types of biliary stenosis(anastomotic stenosis,nonanastomotic peripheral stenosis and non-anastomotic central hilar stenosis)have been identified.We report the outcome of two patients with anastomotic stricture after liver transplantation who underwent successfulcutting balloon treatment.Case 1 was a 40-year-old male transplanted due to subacute fulminant hepatitis C.Case 2 was a 57-year-old male transplanted due to hepatitis B virus-related end-stage cirrhosis associated with hepatocellular carcinoma.Both patients had similar clinical scenarios:refractory anastomotic stenosis after orthotopic liver transplantation and failure of balloon dilation of the common bile duct to alleviate biliary stricture.
基金supported by grants from the National Natural Science Foundation of China(Nos.81900597,81970567)the Natural Science Foundation of Guangdong Province,China(Nos.2019A1515011698,2021A1515012136,2021A1515010571,2018A030313043)+2 种基金Science and Technology Program of Guangzhou City(No.201803040005)National Bioengineering Research Center Cultivation Platform(No.WW201905)the Major Talent Project Cultivation Plan Project(No.P02093).
文摘To the Editor:Despite dramatic improvements in the prognosis of pediatric liver transplantation(LT),postoperative complications are still a leading cause of death in grafts and patients.Child recipients were shown to have a higher risk of thrombotic complications than in adult recipients,due to differences in etiology,narrowed hepatic vessels due to hypoplasia,more meticulous surgical techniques,and other factors.[1]Thrombotic complications include hepatic artery thrombosis(HAT).
基金National Science and Technology Major Project of China,No.2017ZX10203205National Natural Science Funds for Distinguished Young Scholar of China,No.81625003National Natural Science Foundation of China,No.81930016.
文摘Metabolic disease,including diabetes mellitus,hypertension,dyslipidemia,obesity,and hyperuricemia,is a common complication after liver transplantation and a risk factor for cardiovascular disease and death.The development of metabolic disease is closely related to the side effects of immunosuppressants.Therefore,optimization of the immunosuppressive regimen is very important for the prevention and treatment of metabolic disease.The Chinese Society of Organ Transplantation has developed an expert consensus on the management of metabolic diseases in Chinese liver transplant recipients based on recent studies.Emphasis is placed on the risk factors of metabolic diseases,the effect of immunosuppressants on metabolic disease,and the prevention and treatment of metabolic diseases.
基金supported by grants from the National Natural Science Foundation of China(81572368)Guangdong Natural Science Foundation(2016A030313278)+1 种基金Science and Technology Planning Project of Guangdong Province,China(2014A020212084)National Natural Science Youth Foundation of China(81600505)
文摘BACKGROUND: With the expansion of surgical criteria, the comparative efficacy between surgical resection (SR) and liver transplantation (LT) for hepatocellular carcinoma is inconclusive. This study aimed to develop a prognostic nomogram for predicting recurrence-free survival of hepatocellular carcinoma patients after resection and explored the possibility of using nomogram as treatment algorithm reference. METHODS: From 2003 to 2012, 310 hepatocellular carcinoma patients within Hangzhou criteria undergoing resection or liver transplantation were included. Total tumor volume, albumin level, HBV DNA copies and portal hypertension were included for constructing the nomogram. The resection patients were stratified into low- and high-risk groups by the median nomogram score of 116. Independent risk factors were identified and a visually orientated nomogram was constructed using a Cox proportional hazards model to predict the recurrence risk for SR patients. RESULTS: The low-risk SR group had better outcomes compared with the high-risk SR group (3-year recurrence-free survival rate, 71.1% vs 35.9%; 3-year overall survival rate, 89.8% vs 78.9%, both P<0.001). The high-risk SR group was associated with a worse recurrence-free survival rate but similar overall survival rate compared with the transplantation group (3-year recurrence-free survival rate, 35.9% vs 74.1%, P<0.001; 3-year overall survival rate, 78.9% vs 79.6%, P>0.05). CONCLUSIONS: This nomogram offers individualized recurrence risk evaluation for hepatocellular carcinoma patients within Hangzhou criteria receiving resection. Transplantation should be considered the first-line treatment for high risk patients.
基金National Natural Science Foundation of China(No.82270690 and 82200732)Natural Science Foundation of Guangdong Province(No.2021A1515012382,2022A1515011919 and 2022A1515012519).
文摘Liver transplantation(LT)is the only effective treatment for hepatopulmonary syndrome(HPS).Moreover,perioperative refractory hypoxemia(pRH)is a prevalent life-threatening condition and has extremely limited treatment options.Here,we report three patients with HPS who experienced pRH after LT and were consecutively treated with different salvage therapies,ephedrine inhalation,intravenous use of methylene blue with nitric oxide(NO)inhalation,and NO inhalation alone.The results showed that unresolved severe hypoxia may induce fatal morbidity such as early biliary leakage and acute kidney injury.Early initiation of NO inhalation,rather than ephedrine,can significantly improve oxygenation in patients with pRH and may help prevent hypoxia-related complications.Therefore,based on the response to these exploratory salvage treatments,we further demonstrate the unique ventilation-perfusion mismatch pathophysiology in specific lung regions during pRH in HPS.We propose that early inhalation of NO is an important treatment option to rescue severe hypoxia in patients with HPS during the perioperative period of LT.
基金Supported by National Natural Science Foundation of China,No.81372243,No.81570593 and No.81370575Key Scientific and Technological Projects of Guangdong Province,No.2014B020228003 and No.2014B030301041+2 种基金Natural Science Foundation of Guangdong Province,No.2015A030312013Science and Technology Planning Project of Guangzhou,No.201400000001-3,No.201508020262 and No.2014J4100128Science and Technology Planning Project of Guangdong Province,No.2017A020215178
文摘AIM To perform a meta-analysis on laparoscopic hepatectomy VS conventional liver resection for treating hepatolithiasis.METHODS We conducted a systematic literature search on Pub Med,Embase,Web of Science and Cochrane Library,and undertook a meta-analysis to compare the efficacy and safety of laparoscopic hepatectomy V S conventional open liver resection for local hepatolithiasis in the left or right lobe. Intraoperative and postoperative outcomes(time,estimated blood loss,blood transfusion rate,postoperative intestinal function recovery time,length of hospital stay,postoperative complication rate,initial residual stone,final residual stone and stone recurrence) were analyzed systematically.RESULTS A comprehensive literature search retrieved 16 publications with a total of 1329 cases. Meta-analysis of these studies showed that the laparoscopic approach for hepatolithiasis was associated with significantly less intraoperative estimated blood loss [weighted mean difference(WMD): 61.56,95% confidence interval(CI): 14.91-108.20,P = 0.01],lower blood transfusion rate [odds ratio(OR): 0.41,95%CI: 0.22-0.79,P = 0.008],shorter intestinal function recovery time(WMD: 0.98,95%CI: 0.47-1.48,P = 0.01),lower total postoperative complication rate(OR: 0.52,95%CI: 0.39-0.70,P < 0.0001) and shorter stay in hospital(WMD: 3.32,95%CI: 2.32-4.32,P < 0.00001). In addition,our results showed no significant differences between the two groups in operative time(WMD: 21.49,95%CI: 0.27-43.24,P = 0.05),residual stones(OR: 0.79,95%CI: 0.50-1.25,P = 0.31) and stone recurrence(OR: 0.34,95%CI: 0.11-1.08,P = 0.07). Furthermore,with subgroups analysis,our results proved that the laparoscopic approach for hepatolithiasis in the left lateral lobe and left side could achieve satisfactory therapeutic effects. CONCLUSION The laparoscopic approach is safe and effective,with less intraoperative estimated blood loss,fewer postoperative complications,reduced length of hospital stay and shorter intestinal function recovery time than with conventional approaches.
基金Guangdong Basic and Applied Basic Research Foundation,No.2019A1515110654the National Natural Science Foundation of China,No.82103448China Organ Transplantation Development Foundation,No.YZLC-2021-003.
文摘The disease burden related to hepatocellular carcinoma(HCC) is increasing. Most HCC patients are diagnosed at the advanced stage and multikinase inhibitors have been the only treatment choice for them. Recently, the approval of immune checkpoint inhibitors(ICIs) has provided a new therapeutic strategy for HCC. It is noteworthy that the positive outcomes of the phase Ⅲ clinical trial IMBrave150 [atezolizumab(anti-programmed cell death ligand 1 antibody) combined with bevacizumab(anti-vascular endothelial growth factor monoclonal antibody)],showed that overall survival and progression-free survival were significantly better with sorafenib. This combination therapy has become the new standard therapy for advanced HCC and has also attracted more attention in the treatment of HCC with anti-angiogenesis-immune combination therapy. Currently, the synergistic antitumor efficacy of this combination has been shown in many preclinical and clinical studies. In this review, we discuss the mechanism and clinical application of anti-angiogenics and immunotherapy in HCC, outline the relevant mechanism and rationality of the combined application of antiangiogenics and ICIs, and point out the existing challenges of the combination therapy.
基金This work was supported by the Guangdong Provincial Natural Science Foundation(2019A1515011106,2021A1515012382,2022A1515011919)National Natural Science Foundation of China(81972286,81770648,81972151)+2 种基金Guangdong Provincial Transplantation Medicine Engineering Laboratory(A04097)Guangdong Provincial Key Research and Development Project(2019B020236003)The Third Affiliated Hospital of Sun Yat-sen University Five Five-Year Engineering Projects-National Bioengineering Research Institute Development Platform(WW201905(2021)).
文摘Acute-on-chronic liver failure(ACLF)can be cured by liver transplantation;however,perioperative complications still affect posttransplant outcomes.In recent years,early rehabilitation for critical illness,liver disease,and surgery have significantly improved organ reserve function,surgery tolerance,and postoperative quality of life.They could also be applied in the perioperative period of liver transplantation in patients with ACLF.Therefore,the Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association,the Organ Transplant Committee of China Association Rehabilitation Medicine,and the Guangdong Medical Doctor Association of Organ Transplantation conducted a comprehensive review of rehabilitation in end-stage liver disease,critical illness and surgical patients by summarizing current evidence and best clinical practices and proposed a practice consensus on evaluation of cardiopulmonary and physical function,rehabilitation or physiotherapies,as well as the safety concerns in perioperative liver transplant recipients.It will be a valuable resource for hepatologists,transplant surgeons,and intensivists as they care for ACLF patients during transplantation.
基金This study was partly supported by the National Natural Science Foundation of China(82122069,82073869,30900650,81372501,81572260,81773299,and H2808/82330065)Guangdong Basic and Applied Basic Research Foundation(2021B1515020004,2020B1515120032,2021B1212040017,and 2023B03J0106,China)+1 种基金the Fundamental Research Funds for the Central Universities(23yxqntd001,China)the Opening Project of Guangdong Provincial Key Laboratory of New Drug Design and Evaluation(2020B1212060034,China).
文摘Lenvatinib,a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer,facing limitations due to drug resistance.Here,we applied a multidimensional,high-throughput screening platform comprising patient-derived resistant liver tumor cells(PDCs),organoids(PDOs),and xenografts(PDXs)to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings.Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment,expediting drug repurposing screens.Pharmacological screening identified romidepsin,YM155,apitolisib,NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models.Notably,romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway.A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models.Collectively,our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer,providing a feasible multidimensional platform for personalized medicine.
基金grants from the National Science and Technology Major Project of China(No.2017ZX10203205)the National Natural Science Founds for Distinguished Young Scholar of China(No.81625003)+1 种基金the State Key Program of National Natural Science Foundation of China(No.81930016)the National Natural Science Foundation of China(No.81902407).
文摘Background:The downstaging of hepatocellular carcinoma(HCC)has been confirmed to benefit liver transplantation(LT)patients whose tumors are beyond the transplantation criteria.Milan criteria(MC),a tumor size and number-based assessment,is currently used as the endpoint in these patients.However,many studies believe that tumor biological behavior should be added to the evaluation criteria for downstaging efficacy.Hence,this study aimed to explore the feasibility of Hangzhou criteria(HC),which introduced tumor grading and alpha-fetoprotein in addition to tumor size and number,as an endpoint of downstaging.Methods:We performed a multicenter and retrospective study of 206 patients accepted locoregional therapy(LRT)as downstaging/bridge treatment prior to LT in three centers of China.Results:Recipients were divided into four groups:failed downstaging to the HC(group A,n=46),successful downstaging to the HC(group B,n=30),remained within the HC all the time(group C,n=113),and tumor progressed(group D,n=17).The 3-year HCC recurrence probabilities of groups B and C were not significantly different(10.3%vs.11.6%,P=0.87).The HCC recurrent rate was significantly higher in group A(52.3%)compared with that in group B/C(P<0.05).Seven patients(7/76,9.2%)whose tumor exceeded the the HC were successfully downstaged to the MC,and 39.5%(30/76)to the the HC.In group B,23 patients remained beyond the MC and their survivals were as well as those of patients within the MC.Conclusions:Compared to the MC,HC downstaging criteria can give more HCC patients access to LT and furthermore,the outcome of these patients is the same as those matching MC downstaging criteria.Hangzhou downstaging criteria therefore is applicable in clinical practice.
基金This work was supported by the Natural Science Foundation of Guangdong Province of China(No.2019A1515011850).
文摘Indocyanine green(ICG)is a fluorescent dye that is widely used in hepatobiliary surgery for fluorescence contrast.ICG is selectively absorbed by the liver after intravenous injection and then secreted into the bile.ICG's unique catabolism and fluorescence characteristics allow for multiple applications in liver transplantation.We have divided the applications of ICG fluorescence imaging in liver transplantation into:(i)cholangiography,(ii)evaluation of liver transplantation vessels,(iii)liver mapping,and(iv)evaluation of donor liver quality.In this review,we summarize the current status of applications of ICG fluorescence imaging in liver transplantation.
基金supported by the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS)2017-I2M-1-001.
文摘Pancreatic neuroendocrine neoplasms(pNENs)are highly heterogeneous,and the management of pNENs patients can be intractable.To address this challenge,an expert committee was established on behalf of the Chinese Pancreatic Surgery Association,which consisted of surgical oncologists,gastroenterologists,medical oncologists,endocrinologists,radiologists,pathologists,and nuclear medicine specialists.By reviewing the important issues regarding the diagnosis and treatment of pNENs,the committee concluded evidence-based statements and recommendations in this article,in order to further improve the management of pNENs patients in China.
基金This work was supported by the National 13th Five-Year Science and Technology Plan Major Projects of China(2017ZX10203205-006-001,2017ZX10203205-001-003)Guangdong Natural Science Foundation(2016A030313278)+1 种基金Science and Technology Program of Guangdong Province(2017B020209004,20,169,013)Guangdong Key Laboratory of Liver Disease Research(2017B030314027).
文摘Patients with recurrent hepatocellular carcinoma(HCC)following liver transplantation(LT)have a poor prognosis owing to rapid tumor progression.Yttrium-90 radioembolization(^(90)Y-RE)has been shown to be a safe and efficacious transarterial radioembolization treatment for patients with advanced HCC.However,to our knowledge,no data are available for patients with recurrent HCC following LT.Here we report a case of severe bile duct complication after transarterial radioembolization with yttrium-90 in a patient who experienced HCC recurrence following LT.The present case suggests that ^(90)Y-RE should be cautiously performed in patients with recurrent HCC following LT.
基金This work was supported by National 13th Five-Year Science and Technology Plan Major Projects of China(2017ZX10203205 to G.Chen)National Key R&D Plan(2017YFA0104304 to Y.Yang)+6 种基金Na-tional Natural Science Foundation of China(81770648 to Y.Yang)Guangdong Natural Science Foundation(2015A030312013 to Y.Yang)Science and Technology Program of Guangdong Province(2017B020209004 and 2017B030314027 to G.Chen)Science and Technology Program of Guangzhou city(201508020262 to Y.Yang)Collaborative Innovation Major Special Projects of Guangzhou City(201604020007 to F.Yang)Project funded by China Postdoctoral Science Foundation(2019M653904XB to F.Yang)Natural Science Foundation of Xinjiang Uyghur Autonomous Region(2020D01C006 to F.Yang).
文摘Background and aim:Coronavirus disease 2019(COVID-19)is a life-threatening disease that predomi-nantly causes respiratory failure.The impact of COVID-19 on other organs remains elusive.Herein,we aimed to investigate the effects of COVID-19 on the hepatobiliary system.Methods:In the current study,we obtained the clinical records and laboratory results from 66 laboratory-confirmed patients with COVID-19 at the Wuhan Tongji Hospital between 10 February 2020 and 28 February 2020.The detailed clinical features and laboratory findings were collected for analysis.Bioinformatics analysis was conducted to evaluate the correlation between gamma-glutamyl transferase(GGT)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry receptor angiotensin-converting enzyme 2(ACE2).Results:In this cohort,30(51.7%)patients had abnormal liver function on admission,which was asso-ciated with disease severity and enriched in the male and diabetic patients.The elevated levels of direct bilirubin(P¼0.029)and GGT(P¼0.004)were common in patients with severe pneumonia when compared with those with mild pneumonia.In addition,elevated levels of GGT(P¼0.003)and aspartate aminotransferase(AST)(P¼0.007)were positively associated with longer hospital stay.The expression of ACE2 was closely associated with GGT in various human tissues because they shared the common transcriptional regulator hepatic nuclear factor-1 b(HNF1B).Conclusions:Increased GGT levels were common in severe cases and elevated GGT levels were positively associated with prolonged hospital stay and disease severity.Due to the consistent expression with ACE2,GGT is a potent biomarker indicating the susceptibility of SARS-CoV-2 infection.
基金supported by:the National Natural Science Foundation of China(81702393,81770648,81670601,81570593)Key Scientific and Technological Projects of Guangdong Province(2015B020226004,2017A020215178)+4 种基金Guangdong Natural Science Foundation(2017A030310373,2015A030312013)Science and Technology Planning Project of Guangdong Province(2017B030314027,2017B020209004,2015B020226004)Science and Technology Planning Project of Guangzhou(2014Y2e00544)Guangzhou Science and Technology Huimin Special Project(2014Y2e00200)Sun Yat-sen University Young Teacher Training Project(17ykpy47).
文摘Background:Abnormal expression of long non-coding RNAs(lncRNAs)has been found in almost all tumors in humans,providing numerous potential diagnostic and prognostic biomarkers,and therapeutic targets.Materials and methods:The Cancer Genome Atlas(TCGA)database was used to screen potential LncRNAs,and 30 paired hepatocellular carcinoma(HCC)tissues were used to investigate RP11-307C12.11 expression levels by qRT-PCR and another 105 HCC tissues by in situ hybridizsation(ISH).RP11-307C12.11 overexpression and knockdown experiments were performed to investigate the effects of RP11-307C12.11 on HCC growth through in vitro and in vivo assays(MTT assay,colony formation assay,EdU assay,and xenograft model).The molecular mechanism underlying these effects was confirmed by MS2-RIP-assay,RIP assay,luciferase assay,and rescue experiments.Results:RP11-307C12.11 expression level was significantly higher in tumor tissues than in the adjacent normal tissues.Elevated RP11-307C12.11 expression level was associated with poor prognosis of HCC patients,and it may be represented as an independent prognostic biomarker in patients with HCC.Functionally,RP11-307C12.11 overexpression promoted HCC growth both in vitro and in vivo;however,its knockdown reversed these effects.Mechanistically,we found that RP11-307C12.11 expressed predominantly in the cytoplasm and sponged microRNA(miR)-138 to regulate its common target CCND1 and PDK1.Conclusions:Thus,we found that RP11-307C12.11 acts as an oncogene in HCC by binding to miR-138,which might provide a novel target for HCC therapy.
基金This work was supported by:National 13th Five-Year Science and Technology Plan Major Projects of China(2017ZX10203205)National Key R&D Plan(2017YFA0104304)+6 种基金National Natural Science Foundation of China(81770648,81972286)Guangdong Natural Science Foundation(2018A030313259,2015A030312013)Science and Technology Program of Guangdong Province(2017B020209004,20169013,2020B1212060019)Science and Technology Program of Guangzhou City(201508020262)Guangdong Basic and Applied Basic Research Foundation(2019A1515110654,2020A1515010574)the Fundamental Research Funds for the Central Universities(20ykpy38)and China Postdoctoral Science Foundation(2019TQ0369,2020M672987).
文摘Advances in the field of stem cells have led to the development of a technology called organoids.Organoids are cell cluster structures formed by the cultivation of stem cells in a three-dimensional environment in vitro,and they can simulate the living environment of cells in vivo.Organoids play an important role in the screening of drugs for tumor therapy.Compared with traditional drug screening models,tumor organoid models derived from patient tumors have higher sensitivity,heterogeneity,and stability and can restore the real situation of tumors more effectively.Researchers have conducted a number of researches on the feasibility of using organoid technology in drug screening.By testing and comparing the effects of antitumor drugs in organoids and primary tumors,we can select the most appropriate treatment drugs for patients.In the past ten years,organoids from dozens of tissues and biological sample banks from several main organs have been established,and a large number of anticancer drugs have been screened out.This article summarizes the advantages and disadvantages of traditional drug screening models,discusses the development history of organoid technology,and reviews the research results on organoids from tumor drug screening.In addition,the combination of organoid technology and other modern biotechnologies is put forward to further promote the role of organoid technology in the medical field.Finally,this article reviews the history,progress,and prospect on organoids from the view of antitumor drug screening.
