Clinical application of robotic-assistant living donor left lateral segmentectomy / 中华器官移植杂志

Objective:To explore the feasibility and safety of robotic-assisted living donor left lateral segmentectomy (LDLLS) in a large pediatric liver transplant program.Methods:Retrospective analysis was performed for clinical data of 45 LDLLS donors and recipients from June 2021 to September 2022.Traditional open donor liver resection (n=30) and robotic-assisted segmentectomy (n=15) were performed.Two groups were compared with regards to operative duration, intraoperative hemorrhage, postoperative healing and postoperative complications.SPSS 21.0 was utilized for statistical analysis.Independent sample T, paired sample T, Wilcoxon rank sum and Chi-square tests were performed for examining the inter-group differences.Results:Operative duration of robot-assisted surgery group was substantially longer than that of traditional open surgery group ( P<0.001). Intraoperative blood loss was less in robot-assisted surgery group was less than that in traditional open surgery group[(106.0±39.8) vs.(251.0±144.8) ml, P=0.001]. Postoperative hospital stay of robot-assisted surgery group was shorter than that of traditional open surgery group[6.0(6.0, 6.0) vs.7.0(6.0, 9.0), P<0.05]. Two cases of postoperative biliary leakage were observed in donor of traditional open surgery group.Among 2 cases of abdominal infection, one was due to biliary leakage from liver section and secondary surgery was then performed.One case of incisional infection and another case of thrombosis occurred in donor of traditional open surgery group.In robot-assisted surgery group, only one donor had amylase elevation.In traditional open surgery group, there were one case of local thrombosis in middle hepatic vein and one case of bile duct stricture.No long-term complications occurred in robot-assisted surgery group during a follow-up period of over 6 months.Finally recipient data analysis indicated that no significant inter-group differences existed in operative duration, intraoperative blood loss, postoperative hospital stay or postoperative abdominal infection ( P=0.634, P=0.180, P=0.86 and P=0.153). Conclusions:Robotic-assisted LDLLS proves to be be a safe and reliable option for living donor segmentectomy.It is superior to conventional LDLLS in terms of shorter hospital stay, less intraoperative blood loss and fewer postoperative complications.

Role of the criteria based on preoperative serological indexes of AFP and GGT in predicting long-term survival of patients with hepatocellular carcinoma after liver transplantation / 器官移植

Objective To evaluate the role of preoperative serological indexes in predicting long-term survival and tumor recurrence of hepatocellular carcinoma (HCC) patients after liver transplantation, aiming to explore its significance in expanding the Milan criteria. Methods Clinical data of 669 recipients undergoing liver transplantation for HCC were retrospectively analyzed. The optimal cut-off value was calculated by the receiver operating characteristic (ROC) curve. The risk factors affecting the overall survival and recurrence-free survival rates of HCC patients after liver transplantation were identified by univariate and multivariate regression analyses. The correlation between preoperative serum liver enzymes and pathological characteristics in HCC patients was analyzed. The predictive values of alpha-fetoprotein (AFP) combined with γ -glutamyl transferase (GGT) and different liver transplant criteria for the survival and recurrence of HCC patients after liver transplantation were compared. Results Exceeded Milan criteria, total tumor diameter (TTD) > 8 cm, AFP > 200 ng/mL and GGT > 84 U/L were the independent risk factors for the overall survival and recurrence-free survival rates of HCC patients after liver transplantation (all P < 0.05). Correlation analysis showed that preoperative serum GGT level was correlated with TTD, number of tumor, venous invasion, microsatellite lesions, capsular invasion, tumor, node, metastasis (TNM) stage, Child-Pugh score and exceeded Milan criteria (all P < 0.05). Milan-AFP-GGT-TTD (M-AGT) criteria were proposed by combining Milan criteria, TTD with serum liver enzyme indexes (AFP and GGT). The 5-year overall survival and recurrence-free survival rates of HCC recipients who met the M-AGT criteria (111 cases of exceeded Milan criteria) were significantly higher than those who met Hangzhou criteria (both P < 0.05), whereas had no significant difference from their counterparts who met the University of California at San Francisco (UCSF) criteria (both P > 0.05). Conclusions Preoperative serological indexes of AFP and GGT could effectively predict the long-term survival and tumor recurrence of HCC patients after liver transplantation. Establishing the M-AGT criteria based on serological indexes contributes to expanding the Milan criteria, which is convenient and feasible.

Management experience of brain metastasis after liver transplantation for hepatocellular carcinoma / 中华器官移植杂志

Objective:To explore the pathogenesis and prognostic factors of brain metastasis of hepatocellular carcinoma(HCC)after liver transplantation(LT).Methods:Retrospective review was performed for 17 HCC cases with brain metastasis after liver transplantation from 2000 to 2020.All cases were diagnosed as hepatitis B cirrhosis complicated with HCC.All of them were beyond the Milan Criteria.The immunosuppressive regimen consisted of baliximab + mycophenolate mofetil + calcineurin inhibitors(CNIs)+ corticosteroids in early postoperative period with a gradual tapering of corticosteroids and mycophenolate mofetil.Three patients received sirolimus immunotherapy after tumor recurrence and withdrew CNIs.One of three cases received sorafenib.Results:Other organ involvements included lung metastasis( n=16, 94.1%), bone metastasis( n=5, 29.4%)and liver metastasis( n=6, 35.3%). The median survival time after brain metastasis was 7 months and the 1-year cumulative survival rate 29.4%.The median survival time post-LT was 14 months and the 1-year cumulative survival rate 64.7%.Among 7 patients with a resection of brain metastasis, two deaths at Month 1 post-operation were due to cerebral hemorrhage.The longest survival time was 214 months and the median survival time 9 months. Conclusions:The prognosis of brain metastasis post-LT remains poor.However, early detection and reasonable treatment can prolong patient survival time and even achieve long-term survival.Most brain metastases are accompanied by lung metastases.And the finding of lung metastatic tumor hints at a presence of intracranial lesions.

Advances in the clinical research on liver transplantation in treatment of acute-on-chronic liver failure / 临床肝胆病杂志

Acute-on-chronic liver failure (ACLF) is a disease of rapid deterioration of liver function caused by the acute exacerbation of chronic liver diseases, and it is often associated with multiple organ failure and has a poorer prognosis than common liver cirrhosis. Many studies suggest that timely liver transplantation can significantly improve the survival rate of patients with ACLF; however, there are currently no reliable guidelines that point out the indications for liver transplantation in patients with ACLF. This article summarizes recent studies and discusses the indication, timing, and prognosis of liver transplantation in ALCF patients.

Analysis of the clinical factors related to fibrosis after pediatric liver transplantation / 中华器官移植杂志

Objective:To explore the clinicalfactors related to allograft fibrosis after pediatric liver transplantation.Methods:The clinical data were respectively analyzed for 94 pediatric recipients from January 2013 to December 2016 at Tianjin First Central Hospital.The Patients were assigned into fibrotic and non-fibrotic groups based upon the results of protocol liver biopsies. Univariate and multivariate Logistic regression analyses were performed for examining the risk factors of fibrosis after pediatric livertransplantation. Then Logistic regression model was established to obtain the predicted value of combined predictive factors.Thereceiver operating characteristic curve (ROC) was conducted to evaluate the predictive value of combined predictive factors.Results:A total number of 54(57.5%) patients occurred fibrosis among the 94 patients. There weresignificant differences in cold ischemia time (Z=2.094), warm ischemia time (Z=2.421), biliary stricture( χ2=4.560), drug-induced liver injury ( χ2=7.389), hepatic artery thrombosis and rejection ( χ2=6.955)between two groups ( P<0.05). Logistic regression analysis showed that cold ischemia time (OR=1.003, 95%CI: 1.000~1.007, P=0.044), biliary stricture(OR=6.451, 95%CI: 1.205~33.295), rejection(OR=2.735, 95%CI: 1.057~7.077)and drug-induced liver injury (OR=4.977, 95%CI: 1.207~20.522, P=0.026) were independent risk factors for fibrosis 5 years after liver transplantation. The area under the ROC curve was 0.786(95%CI: 0.691~0.881), for predicting patient outcome.If using 0.311as a cutoff Value, the sensitivity was 90.70%, and the specificity was 60.00%. However, through the ROC curve comparison, there was statistical significance between combined predictive factors and the other independent risk factors ( P>0.05). Conclusions:The incidence of fibrosis 5 years after pediatricliver transplantation is 57.5%. Prolonged cold ischemia time, biliarystricture, rejectionand drug-induced liver injury after liver transplantation are independent risk factors for fibrosis 5 years after pediatric liver transplantation.And the combined predictive factors have a high predictive value forallograftfibrosis.

A study on resectable hilar cholangiocarcinoma comparing neoadjuvant therapy combined with liver transplantation versus radical hepatectomy / 中华肝胆外科杂志

Objective:To compare the treatment outcomes of neoadjoint therapy combined with liver transplantation versus radical hepatectomy for patients with surgically resectable hilar cholangiocarcinoma.Methods:A retrospective study was performed on the data of 64 patients with resectable hilar cholangiocarcinoma operated from January 2009 to December 2014 at the Organ Transplantation Department of the First Central Hospital of Tianjin. There were 43 males and 21 females, with an average age of 61.2 years. There were 45 patients who underwent radical hepatectomy in the liver resection group, and 19 patients who underwent combined neoadjuvant therapy (radiotherapy combined with 5-fluorouracil intravenous drip, transcatheter lumen radiotherapy, capecitabine oral administration) and liver transplantation in the liver transplantation group. The recurrence rates and survival rate were compared between groups.Results:The 1, 3 and 5 years cumulative survival rates of the liver transplantation group were 89.5%, 73.7% and 63.2%, respectively, which were significantly better than those of the liver resection group (80.0%, 53.3% and 35.6%) ( P<0.05). The postoperative tumor recurrence rate in the liver transplantation group was 31.6% (6/19), which was significantly lower than that in the liver resection group of 60.0% (27/45) ( P<0.05). Subgroup analysis using postoperative pathological results showed the cumulative survival rates of patients without lymph node metastasis (N 0) and those with negative resection margins (R 0) were not significantly different between groups ( P>0.05). However, for patients with regional lymph node invasion (N 1) and with R 0 resection margin, the cumulative survival rates at 1, 3 and 5 years after liver transplantation were 83.3%, 66.7% and 50.0%, respectively, which were significantly superior to the 64.3%, 28.6% and 14.3% of the liver resection group ( P<0.05). Conclusion:Hepatectomy is recommended for patients with N 0 R 0 resectable hilar cholangiocarcinoma. For patients with hilar cholangiocarcinoma with marginally resectable N 1R 0, neoadjuvant therapy combined with liver transplantation resulted in significantly better long-term overall survival than resection.

Combined Laparoscopic spleen-preserving distal pancreatectomy and autologous islet transplantation: report of one case and literature review / 中华器官移植杂志

Objective:To Eveluate the safty and clinical efficacy of combined laparoscopic spleen-preserving distal pancreatectomy and autologous islet transplantation in the treatment of solid pseudopapillary neoplasm.Methods:A 22 years old solid pseudopapillary neoplasm female patient who underwent distal pancreatectomy and an autologous islet transplantation at Tianjin First Central Hospital, clinical date for 6 months follow up was collected and analyzed.Results:The patient was well recovered after surgery, and during the post-operative follow up, the fasting blood glucose was 5.72 mmol/L, HbA1c was 6.1%, remained insulin independent, the liver function was kept well.Conclusions:Combined Laparoscopic spleen-preserving distal pancreatectomy and autologous islet transplantation can effectively prevent diabetes after distal pancreatectomy.

Role of HO-1/BMMSCs in improving hepatic microcirculation after reduced-size transplantation in rats / 中华器官移植杂志

Objective:To explore the role of heme oxygenase-1 (HO-1) modified bone marrow mesenchymal stem cells (BMMSCs) in improving hepatic microcirculation after reduced-size liver transplantation (RLT) in rats.Methods:BMMSCs were isolated and cultured in vitro by adherence method. Then HO-1/adenovirus (Adv) was transfected for constructing HO-1/BMMSCs. The "dual-sleeve" method was employed for establishing an acute rejection model after 50% RLT. Immediately post-operation, 1 ml normal saline (NS) and BMMSCs or HO-1/BMMSCs single cell suspension were injected. The changes of surviving rats were observed by parameters at Day 3/7/14 post-operation. Five rats were observed at each timepoint. The serum level of mitochondrial aspartate aminotransferase (mAST) was detected; Na+ -K+ -ATPase in transplanted liver was measured by chemical colorimetry; mitochondrial ultrastructural changes were observed under a transmission electron microscope. Portal vein pressure was detected by Power Lab at Day 7 post-operation; the expressions of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and von Willebrand factor (vWF) in liver tissues were detected by Western blot. Liver histopathological changes were observed by hematoxylin & eosin stain. The expression of vWF was detected by immunohistochemistry and serum level of hyaluronic acid (HA) detected by enzyme-linked immunosorbent assay (ELISA).Results:HO-1/BMMSCs could significantly lessen the pathological injury and rejection of 50% reduced-size transplanted liver, improve mitochondrial damage and energy metabolism, promote the expression of eNOS, suppress the expression of iNOS, reduce portal pressure, up-regulate the expression of hepatic sinus vWF and HA degradation, protect hepatic sinusoidal endothelial cells (SECs) and ultimately improve hepatic microcirculation. And the differences were statistically significant as compared with NS/BMMSCs group ( P<0.05). Conclusions:HO-1/BMMSCs may play an important role in protecting rat liver by improving hepatic microcirculation during RLT.

Progress in research on donor liver preservation technology in vitro / 中华肝胆外科杂志

Liver transplantation is the most effective therapeutic options for the patients at the advanced stage, but with the amount of transplant surgery increasing, margin donors are used for transplantation in the case of severe donor organ deficiency. However, the commonly used cold storage technique has poor preservation effect on margin donors, resulting in an increase in the incidence of complications after transplantation. The donated liver quality is one the most important factors for the patients long term survival, so there is an urgent need for a new type of organ preservation technology to preserve the margin donors in vitro. This paper summarized the current research on the ex-vivo preservation methods of liver and the new mechanical perfusion preservation methods.

The effect of optimized normothermic mechanical perfusion on biliary epithelial cells in liver graft by preserving the donation after cardiac death in rats / 中华肝胆外科杂志

Objective To study the effect of bone marrow mesenchymal stem cells (BMMSCs) combined with normothermic mechanical perfusion (NMP) on biliary epithelial cells (BEC) after DCD donor liver transplantation in rats.Methods The third generation of BMMSCs and the BMMSCs modified by Ad/HO-1 (Ad/HO-1/BMMSCs) were cultured,identified and expanded in vitro.To establish a stable NMP system device in vitro.The DCD liver transplantation models were constructed in rats after cardiac ischemia for 30 minutes,220 SD recipient rats were randomly divided into sham operation group (S group,n=44) static cold storage (SCS group,n =44) group,and simple NMP group (P group,n =44),BMMSCs combined with NMP group (BP group,n =44) and BMMSCs modified by Ad/HO-1 combine with NMP group (HBP group,n =44),NMP group,BP group and HBP group were subjected to vitro perfusion for 4h.The group were taken at 0,1,7 and 14 days after transplantation and the relevant indicators were detected,n =6 in each group.The survival rate of the recipient rats,liver function and pathological changes of the bile duct were observed.The expression of cytokeratin 19 (CK19) protein in BEC was detected by immunohistochemistry and Western blot.Apoptotic biliary epithelial cells were detected by TUNEL staining and the expression of apoptosis-related protein caspase-3 was detected by immunohistochemistry.Results The survival time of HBP group was significantly prolonged for (5.6 ±0.8) d in SCS group vs.(18.4 ±2.0) d in NMP group,(20.5 ± 1.5) d in BP group,(82.5 ±3.2) d in HBP group,the differences were statistically significant (all P ＜ O.05).Compared with other groups,the HBP group and the BP group were significantly improved in liver function and biliary pathology,and the expression of CK19 protein in BEC was significantly increased [(0.81 ±0.02) in S group vs.(0.35 ±0.03) in SCS group,(0.47 ±0.02) in NMP group,(0.63 ± 0.02) in BP group,(0.77 ± 0.01) in HBP group on postoperative day (POD) 14],the differences were statistically significant (all P ＜ 0.05).The number of apoptosis and the expression of apoptosis-related protein caspase-3 in HBP group were significantly decreased [(10.0 ± 1.2) in S group vs.(57.3 ±5.5) in SCS group,(40.1 ±4.6) in NMP group,(32.0 ± 2.2) in BP group,(13.7 ± 3.1) in HBP group on POD 14],the difference was statistically significant (all P ＜ 0.05).Compared with the BP group,the protective effect of the HBP group was more obvious,and the difference was statistically significant (P ＜ 0.05).Conclusion By the method of the BMMSCs modified by Ad/HO-1 combined with NMP in vitro preservation of rat,DCD donor liver can significantly improve the effect of BEC on rats and the survival rate after liver transplantation.

Experimental study on liver ischemia reperfusion injury promoted by NOD1 activated pyroptosis / 中华器官移植杂志

Objective To investigate the effect of nucleotide-binding oligomerization domaincontaining protein 1 (NOD1) on pyroptosis in hepatic ischemia-reperfusion injury.Methods An animal model of ischemia-reperfusion injury was established.Thirty healthy,male,and clean C57 BL mice were randomly divided into sham operation group (sham group) and ischemia-reperfusion group (IR,including 2 h,6 h,12 h,24 h subgroups),6 per group.Serum ALT and AST levels in each group were measured by blood biochemistry.HE staining and TUNEL were used to observe the pathological changes of liver and hepatocyte apoptosis.Immunohistochemistry was used to detect the expression and distribution of NOD1 in each group.Western blotting was used to detect NOD1,MM2,pro-Caspase-1 and active-Caspase-1 expression.NOD1 siRNA and empty control siRNA were transfected into AML12 cells,then the hypoxia/reoxygenation model was established and cells were collected to detect the expression of NOD1,AIM2 and active-Caspase-1.Results The ALT and AST levels in IR group were significantly higher than those in sham group,and peaked at IR 12-h subgroup (P＜0.05).HE staining showed that hepatic injury was the most severe at 12 h after reperfusion.TUNEL results showed that the number of apoptotic cells was the greated at 12 h after reperfusion.Western blotting showed that NOD1 protein expression was highest at 12 h after reperfusion.With the prolongation of reperfusion time,the expression of AIM2 and active-Caspase-1 gradually increased,and that of pro-Caspase-1 gradually decreased.The expression of NOD1,AIM2 and activeCaspase-1 decreased after transfection of NOD1 siRNA into AML12 cells.Conclusions NOD1 promotes liver ischemia-reperfusion injury,which may be related to NOD1 promoting liver injury by activating pyroptosis.

Living donor liver transplantations for pediatric patients withbiliary atresia in a single center: 306 / 中华器官移植杂志

Objective To analyze the clinical efficacy and prognosis of living donor liver transplantation (LDLT) in children with biliary atresia (BA).Methods The clinical data of 306 cases of BA patients who received LDLT from June 2013 to December 2017 in the Department of Pediatric Liver Transplantation of Tianjin First Center Hospital were retrospectively analyzed.The incidence of post-LDLT complications was summarized and different factors influencing long-term survival of the recipients were analyzed.Results The median age of recipients at transplantation was 7 (6,9) months,and 88.9％ of the recipients received left lateral lobes.The surgical-related complications mainly included lymphatic leakage (30.7％),bile duct stricture (7.8％) and portal vein stenosis (6.9％).The non-surgical-related complications were mainly EBV infection (57.8％) and CMV infection (36.6％).The incidence of pulmonary infection and acute rejection was 18.6％ and 13.7％,respectively.The 1-,3-,and 5-year survival rates of recipients and grafts were 97.2％,97.2％,97.2％ and 97.2％,96.4％,and 94.6％,respectively.A total number of 8 patients died after LDLT,mainly due to the complications of cardio-pulmonary system.Two patients underwent retransplantation due to graft dysfunction caused by antibody-mediated rejection.Recipient age,PELD scores,GRWR,previous surgical history and matching of ABO blood group between donors and recipients did not affect the long-term survival rates of recipients (P＞0.05).Conclusions Children with biliary atresia who received LDLT can obtain satisfactory clinical results.

Effect factors of liver enzymes elevation afterintraportal islet transplantation / 中华器官移植杂志

Objective@#To investigate the effect factors of liver enzymes elevation by monitoring the liver function changes before and after intraportal islet transplantation.@*Methods@#16 diabetic patients who received intraportal islet transplantation in our hospital were analyzed. The levels of aspartic aminotransferase (AST), alanine aminotransferase (ALT)and total bilirubin (TBil)were monitored after islet transplantation.@*Results@#Among those 16 diabetic patients who received intraportal islet transplantation, 11 patients showed an increased AST and 8 patients showed an increased ALT, among which a 2.5-fold increase in AST was observed in 4 patients and over 1.5-fold elevation of ALT was observed in 3 patients. The level of TBil were in the normal range before and after transplantation in all patients. Transplanted tissue volume of islet was the main factor for significantly increased AST (P<0.05) in this study. It is also shown that the change in portal pressure is related to the AST elevation after islet transplantation.@*Conclusions@#The amount of transplanted islet tissue volume is related to the liver enzymes elevation after intraportal islet transplantation. Therefore, the improvement of the purity of islet to reduce the amount of transplanted tissue could be benefit to prevent the liver injury after islet transplantation. Meanwhile, the purified islets should be injected as slowly as possible to maintain a stable portal pressure.

Effects of bone marrow mesenchymal stem cells combined with normothermic mechanical perfusion on biliary epithelial cells donated after cardiac death in rats / 中华危重病急救医学

Objective@#To investigate the protective effect of bone marrow mesenchymal stem cells (BMMSC) combined with normothermic mechanical perfusion (NMP) on biliary epithelial cells (BEC) in rats receiving donation after cardiac death (DCD) donor liver transplantation.@*Methods@#The BMMSC were isolated from male Sprague-Dawley (SD) rats aged 2-3 weeks and weighing 40-60 g, and then cultured, identified and expanded to the third generation in vitro. Male SD rats aged 6-8 weeks and weighing 200-220 g were divided into sham-operated group (Sham group), static cold storage (SCS group), simple NMP group (NMP group) and BMMSC combined with NMP group (BMMSC+NMP group) by random number table method with 44 rats in each group. The DCD donor liver transplantation models in rats were reproduced with 30-minute warm ischemic time. While the rats in Sham group merely received perihepatic ligaments-separation, which did not affect their liver blood supply, and then their incisions were sutured after 30 minutes. The DCD donor grafts in SCS group were preserved in the University of Wisconsin (UW) cold storage solution for 4 hours. While the DCD donor grafts in the NMP group and the BMMSC+NMP group were perfused with the DMEM/F12-based culture solution or combined with BMMSC for 4 hours through the established ex vivo NMP system. The orthotopic liver transplantation model was reproduced, and the survival rate of the recipients was observed at 0, 1, 7 and 14 days after liver transplantation. The biochemical liver function of rats in different groups was determined at each time point after operation. The morphological changes in bile ducts of liver grafts were observed by hematoxylin-eosin (HE) staining, and the expression of cytokeratin 19 (CK19) was determined qualitatively by immunohistochemistry and quantitatively by Western Blot after protein extraction from BEC in liver samples.@*Results@#The morphology, differentiation function and phenotypic identification of BMMSC confirmed that the stem cells used in this experiment were standard BMMSC. The survival rates of rats in the NMP group and the BMMSC+NMP group were significantly higher than that in the SCS group at 0, 1, 7 and 14 days after operation. The increase was more significant in the BMMSC+NMP group, with 100% on postoperative day (POD) 0, and the 14-day survival rate was still significantly higher than that in the SCS group and the NMP group [80.0% (16/20) vs. 20.0% (4/20), 70.0% (14/20), both P < 0.05]. As the time after liver transplantation prolonged, the liver function parameters of rats in the SCS group were deteriorated gradually, which reached the peak at 1-7 days after operation. The damage of biliary tissue increased gradually under the microscope, and the injury was most serious on POD 7 in the SCS group, showing a lot of balloon-like changes in hepatocytes, with obvious bile duct dilatation accompanied by large area inflammatory cell infiltration. Immunohistochemistry and Western Blot showed that the expression of CK19 in BEC cytoplasm was decreased gradually in the SCS group, reached the lowest on POD 7, and then gradually increased. The BMMSC+NMP group and the NMP group were significantly better than the SCS group in terms of liver function, pathological injury of biliary tract and CK19 expression in BEC, and the improvement was more significant in the BMMSC+NMP group. These results suggested that the protective effects of BMMSC combined with NMP on BEC was significantly better than that of the SCS and NMP.@*Conclusion@#Preservation of rat DCD donor liver by BMMSC combined with NMP can reduce the BEC injury after liver transplantation significantly, thus improving both the prognosis and the survival rate after transplantation.

Effect factors of liver enzymes elevation afterintraportal islet transplantation / 中华器官移植杂志

Objective To investigate the effect factors of liver enzymes elevation by monitoring the liver function changes before and after intraportal islet transplantation .Methods 16 diabetic patients who received intraportal islet transplantation in our hospital were analyzed .The levels of aspartic aminotransferase (AST ) ,alanine aminotransferase (ALT )and total bilirubin (TBil)were monitored after islet transplantation .Results Among those 16 diabetic patients who received intraportal islet transplantation ,11 patients showed an increased AST and 8 patients showed an increased ALT ,among which a 2 .5-fold increase in AST was observed in 4 patients and over 1 .5-fold elevation of ALT was observed in 3 patients .The level of TBil were in the normal range before and after transplantation in all patients . Transplanted tissue volume of islet was the main factor for significantly increased AST (P< 0 .05) in this study .It is also shown that the change in portal pressure is related to the AST elevation after islet transplantation .Conclusions The amount of transplanted islet tissue volume is related to the liver enzymes elevation after intraportal islet transplantation .Therefore ,the improvement of the purity of islet to reduce the amount of transplanted tissue could be benefit to prevent the liver injury after islet transplantation .Meanwhile ,the purified islets should be injected as slowly as possible to maintain a stable portal pressure .

Risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma and related control strategies / 临床肝胆病杂志

Tumor recurrence after liver transplantation for hepatocellular carcinoma is the main cause of significant reductions in the survival rates of patients and grafts. Risk factors for tumor recurrence after liver transplantation include pathological and biological features, factors associated with the recipient, factors associated with the donor and donor liver, and surgery-related factors. Immunosuppression regimen and various adjuvant therapies may help to prevent tumor recurrence. For patients undergoing liver transplantation for hepatocellular carcinoma, further studies are needed to investigate early identification of risk factors for tumor recurrence and related comprehensive prevention and treatment measures.

Tasks and strategies for the prevention and treatment of middle- and long-term complications after liver transplantation / 临床肝胆病杂志

With the continuous improvement of liver transplantation techniques and the innovation of related disciplines, great changes have been observed in the etiology and clinical outcome of middle- and long-term complications after liver transplantation, and thus related prevention and treatment strategies are worthy of exploration and adjustment. In recent years, breakthroughs have been made in the prevention and treatment of post-transplantation complications including the recurrence of hepatitis, but standardized diagnosis and treatment should be strengthened in order to maximize the benefits of recipients. So far, the prevention and treatment of middle- and long-term complications with unknown pathogenesis and complicated causes after liver transplantation still rely on the long-term monitoring, prevention, and control of related risk factors. The main tasks of long-term management of liver transplantation recipients is to maintain the function of transplanted liver, control the recurrence of primary diseases, prevent and treat the new-onset diseases, and continue to treat the concomitant diseases before surgery. This article elaborates on the tasks and strategies for the prevention and treatment of middle- and long-term complications after liver transplantation.

Effects of bone marrow mesenchymal stem cells combined with normothermic mechanical perfusion on biliary epithelial cells donated after cardiac death in rats / 中华危重病急救医学

Objective To investigate the protective effect of bone marrow mesenchymal stem cells (BMMSC) combined with normothermic mechanical perfusion (NMP) on biliary epithelial cells (BEC) in rats receiving donation after cardiac death (DCD) donor liver transplantation. Methods The BMMSC were isolated from male Sprague-Dawley (SD) rats aged 2-3 weeks and weighing 40-60 g, and then cultured, identified and expanded to the third generation in vitro. Male SD rats aged 6-8 weeks and weighing 200-220 g were divided into sham-operated group (Sham group), static cold storage (SCS group), simple NMP group (NMP group) and BMMSC combined with NMP group (BMMSC+NMP group) by random number table method with 44 rats in each group. The DCD donor liver transplantation models in rats were reproduced with 30-minute warm ischemic time. While the rats in Sham group merely received perihepatic ligaments-separation, which did not affect their liver blood supply, and then their incisions were sutured after 30 minutes. The DCD donor grafts in SCS group were preserved in the University of Wisconsin (UW) cold storage solution for 4 hours. While the DCD donor grafts in the NMP group and the BMMSC+NMP group were perfused with the DMEM/F12-based culture solution or combined with BMMSC for 4 hours through the established ex vivo NMP system. The orthotopic liver transplantation model was reproduced, and the survival rate of the recipients was observed at 0, 1, 7 and 14 days after liver transplantation. The biochemical liver function of rats in different groups was determined at each time point after operation. The morphological changes in bile ducts of liver grafts were observed by hematoxylin-eosin (HE) staining, and the expression of cytokeratin 19 (CK19) was determined qualitatively by immunohistochemistry and quantitatively by Western Blot after protein extraction from BEC in liver samples. Results The morphology, differentiation function and phenotypic identification of BMMSC confirmed that the stem cells used in this experiment were standard BMMSC. The survival rates of rats in the NMP group and the BMMSC+NMP group were significantly higher than that in the SCS group at 0, 1, 7 and 14 days after operation. The increase was more significant in the BMMSC+NMP group, with 100% on postoperative day (POD) 0, and the 14-day survival rate was still significantly higher than that in the SCS group and the NMP group [80.0% (16/20) vs. 20.0% (4/20), 70.0% (14/20), both P < 0.05]. As the time after liver transplantation prolonged, the liver function parameters of rats in the SCS group were deteriorated gradually, which reached the peak at 1-7 days after operation. The damage of biliary tissue increased gradually under the microscope, and the injury was most serious on POD 7 in the SCS group, showing a lot of balloon-like changes in hepatocytes, with obvious bile duct dilatation accompanied by large area inflammatory cell infiltration. Immunohistochemistry and Western Blot showed that the expression of CK19 in BEC cytoplasm was decreased gradually in the SCS group, reached the lowest on POD 7, and then gradually increased. The BMMSC+NMP group and the NMP group were significantly better than the SCS group in terms of liver function, pathological injury of biliary tract and CK19 expression in BEC, and the improvement was more significant in the BMMSC+NMP group. These results suggested that the protective effects of BMMSC combined with NMP on BEC was significantly better than that of the SCS and NMP. Conclusion Preservation of rat DCD donor liver by BMMSC combined with NMP can reduce the BEC injury after liver transplantation significantly, thus improving both the prognosis and the survival rate after transplantation.

Diagnostic and therapeutic experience of portal vein stenosis after pediatric liver transplantation from donation after citizen's death graft:a report of 30 cases / 中华器官移植杂志

Objective To summarize the experiences of diagnosing and treating portal vein stenosis (PVS) after pediatric liver transplantation from China donation after citizen 's death (CDCD) grafts .Methods Retrospective analysis was performed for 30 cases of pediatric CDCD liver transplantation recipients with PVS .The screening ,diagnosis ,treatment and prognosis of PVS were analyzed .Results Among 218 pediatric liver transplantation recipients with CDCD grafts ,PVS was diagnosed in 30 cases with an incidence rate of 13 .8％ (30/218) .The initial diagnosis of PVS ranged from 5 days to 27 months post-operation with a median age of 2 .9 months .Ultrasonography indicated that stenotic rate of anastomotic site diameter was (41 .28 ± 12 .93)％ and blood flow velocity ratio (358 .77 ± 117 .82)％ .Intervention examination showed average pressure gradient was (9 .06 ± 5 .34) mmHg between both sides of stenosis . All cases underwent percutaneous intrahepatic balloon dilatation .The recipients were followed up for a median follow-up time of 23(3-63) months .For three cases of restenosis ,percutaneous intrahepatic balloon dilatation was repeated .Two cases underwent stent implantation due to ineffective balloon dilation .After treatment ,the stenotic rate of anastomotic site diameter was (34 .69 ± 8 .82) and blood flow velocity ratio (61 .18 ± 63 .11)％ on ultrasound while the average pressure gradient was (1 .03 ± 0 .85) mmHg .Conclusions PVS is a common vascular complication after pediatric CDCD liver transplantation .Portal vein balloon dilation is both safe and efficacious .However ,some cases require repeated balloon dilation and stent implantation serves as the last option for intractable PVS .Color ultrasound is both convenient and effective for making a primary diagnosis and evaluating outcomes .

Laminin may be a predictor of recurrence after liver transplantation for HBV -related hepatocellular carcinoma patients / 中华器官移植杂志

Objective To explore the prognostic role of laminin (LN ) as a tumor biological marker in predicting the recurrence of hepatocellular carcinoma (HCC) related with HBV infection after liver transplantation (LT ) .Methods Tissue samples from 251 HBV-related HCC patients undergoing LT were immunohistochemically stained with anti-LN antibody .The relevant prognostic factors were analyzed using Spearman's rank test , Kaplan-Meier method , log-rank test and multivariate step-wise Cox regression analysis .Results The expressions of LN in tumor tissues were significantly positively correlated with tumor number (P=0 .00) ,microsatellite (P=0 .02) ,venous invasion (P=0 .048) ,pTNM tumor stage (P=0 .00) ,pre-LT serum α-fetoprotein (AFP) level (P=0 .00) ,HBV DNA level (P= 0 .02) ,HBeAg level (P= 0 .02) and tumor recurrence (P= 0 .00) respectively .Significant differences existed in 1/3/5-year overall survival or tumor recurrence-free survival rate post-LT among LN different expression (-,+ ,≥ + + ) in HBV-related HCC patients (P< 0 .05 ) . Multivariate analysis indicated that LN was a significantly independent predictor in predicting poor tumor recurrence-free survival post-LT (P=0 .01) .Conclusions LN may be a feasible marker in predicting HCC recurrence post-LT for HBV-related HCC patients .