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Objective:To explore the effect of pre-transplant immunotherapy on the prognosis of transplant recipients with hepatocellular carcinoma(HCC).Methods:From June 2018 to September 2021, retrospective analysis was conducted for clinical data of 19 HCC-liver transplant recipients receiving pre-transplant immunotherapy in affiliated Huashan Hospital of Fudan University. Pre-transplant immunotherapy regimen, adverse reactions, post-transplant acute rejection, tumor recurrence and metastasis and other complications were recorded. According to the preoperative tumor imaging and the changes of alpha-fetoprotein level, tumor change during recipient waiting period was judged by the mRECIST standard. According to whether or not there was partial tumor remission, they were divided into two groups of non-remission( n=13)and remission( n=6). Postoperative conditions of two groups were compared. Kaplan-Meier method was used for calculating the survival rate of recipients after transplantation and survival curve and Log-rank test utilized for comparing the recurrence-free and overall survival rates of recipients at 1 and 2 years post-operation. Results:A total of 19 liver transplant recipients received immunotherapy plus targeted and transcatheter arterial chemoembolization(TACE) before transplant. In non-remission group, tumor was stable( n=9)and progressive( n=4); 6 cases in remission group had tumor partial remission. Two recipients in non-remission group were pathologically confirmed by liver biopsy to have acute rejection(2/19, 10.5%)and both recovered after glucocorticoid + rATG and glucocorticoid therapy. In non-remission group, 2 patients died from septic shock post-operation. Among 3 patients of tumor recurrence and metastasis post-operation, 2 cases survived with tumor and 1 died after tumor recurrence and metastasis. In remission group( n=6), none had postoperative tumor recurrence and metastasis. The recurrence-free survival rates of non-remission group recipients at 1 and 2 years post-operation were 76.9% and 76.9% and recurrence-free survival rates in remission group were 100% and 100% respectively and inter-group difference in RFS was not statistically significant( χ2=1.468, P=0.226). The overall survival rates of recipients in non-remission group at 1 and 2 years post-operation were 76.9% and 76.9% respectively. And recipients in remission group were 100% and 100% respectively and no statistically significant inter-group difference existed in OS( χ2=1.292, P=0.256). Conclusions:Without a significantly higher risk of acute rejection after transplant, immunotherapy may be an effective option for bridging treatment before liver transplantation for HCC. And it remains necessary to expand the sample size for verifications and supports.
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Objective:To compare the prognoses of salvage liver transplantation fulfilling the Criteria of Milan, University of California San Francisco(UCSF)and Hangzhou.Methods:Clinical data were retrospectively reviewed for 256 patients with recurrent hepatocellular carcinoma(HCC)undergoing donation after citizen death(DCD)liver transplantation(LT)from January 2015 to October 2019.They were divided into two groups of primary(PLT, n=175)and salvage(SLT, n=81). General profiles, tumor pathological characteristics and postoperative complications of two groups were compared by T-test, rank-sum or χ2 test.Kaplan-Meier method and Log rank test were employed for comparing overall survival rate(OS)and recurrence-free survival rate(RFS)between two groups.In SLT group, 31 cases fulfilled Milan criteria, 45 cases UCSF criteria and 69 cases Hangzhou criteria.OS/RFS of three groups were compared.According to there was downstaging or bridging treatment pre-LT, SLT group was divided into downstaging group(n=32)and non-downstaging group(n=49). OS/RFS of two groups were compared.According to the Rescit1.1 criteria, downstaging group were divided into remission group(n=14)and non-remission group(n=18)and OS/RFS of two groups were compared. Results:The operative durations of PLT and SLT groups were(439.5±74.9)and(475.1±83.4)min respectively.There was significant inter-group difference( P<0.05); However, no significant inter-group difference existed in amount of intraoperative bleeding, blood transfusion, postoperative hospital stay or incidence of postoperative complications(all P>0.05). No significant difference existed in OS/RFS between PLT and SLT groups( P>0.05). No significant difference existed in OS at 1/3/5 years post-SLT among Milan, UCSF and Hangzhou criteria groups(all P>0.05); However, RFS in Milan criteria group at 1/3/5 years post-SLT were 93.5%, 81.7% and 81.7% respectively.They were significantly higher than 68.9%, 59.7% and 59.7% in UCSF criteria group and 78.3%, 58.8% and 55.5% in Hangzhou criteria group(all P<0.05). For patients on downstaging therapy, OS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 73% and 73% respectively, which was significantly higher than 83.3%, 49.4% and 0 in non-Remission group( P=0.042). RFS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 62.5% and 46.9% respectively, which was significantly higher than 52.9%, 0 and 0 in no-Remission group( P=0.001). Conclusions:The survival outcome of SLT recipients is similar to that of PLT recipients.The overall survival of SLT recipients shows no significant difference between Milan, UCSF and Hangzhou criteria.However, SLT recipients fulfilling Milan criteria have the longest recurrence-free time.The prognosis of patients with remission after preoperative descending treatment is superior to that of patients without remission.
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Objective:To explore the relationship between CD24 expression in preoperative peripheral blood as well as cancer tissue and clinical parameters and prognosis in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT).Methods:From November 2018 to November 2019, clinical data were collected for 65 HCC patients and 41 patients with benign liver disease.The preoperative peripheral blood level of CD24 was detected by enzyme-linked immunosorbent assay (ELISA) and the expression of CD24 in cancerous foci and adjacent tissues examined by immunohistochemistry.Kaplan-Meier survival curves of differential CD24 expression were plotted and survival differences compared by Log-rank method.One-way ANOVA was utilized for examining the relationship between the expression level of CD24 and various clinicopathological parameters and multivariate Cox analysis for screening independent risk factors affecting patient prognosis.Results:The concentration of CD24 in preoperative peripheral blood (p-CD24) of HCC patients (6.51±2.33 μg/L) was significantly higher than that of patients with benign liver disease (4.10±0.91) μg/L, P<0.05.The positive rate of CD24 was obviously higher in cancerous tissues than that in adjacent tissues (87.7% vs. 4.6%, P<0.05). The peripheral blood level of CD24 was positively correlated with the expression intensity of CD24 in tumor tissues (t-CD24, r=0.570, P<0.001). The expression of CD24 (both in blood and cancer foci) was significantly correlated with preoperative level of gamma-glutamyl transferase (GGT), maximal tumor diameter, microvascular invasion, portal vein tumor thrombus, vessel carcinoma embolus and satellite focus ( P<0.05). The expression of CD24 in patients exceeding the Milan/UCSF criteria was higher than those fulfilling the criteria ( P<0.005). Patients with a higher expression of CD24 had worse overall survival and recurrence-free survival rates as compared to those a lower expression of CD24 ( P<0.05). Multivariate Cox analysis indicated that t-CD24 [OS: HR=3.661(1.005-13.333)], P=0.049; recurrence-free survival (RFS): [HR=4.331(1.887-9.942), P=0.001] and preoperative level of alpha fetoprotein (AFP) [OS: HR=4.900(1.590-15.097), P=0.006]; RFS: [HR=3.414(1.614-7.221), P=0.001] were independent risk factors for overall survival and recurrence-free survival in HCC patients undergoing LT. Conclusions:The preoperative peripheral blood level of CD24 in HCC patients undergoing LT indirectly reflects the expression of CD24 in cancerous tissues to a certain extent.And the expression of CD24 in cancerous tissue is one of the independent risk factors affecting OS and RFS of LT patients.
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Objective:To investigate the imaging anatomical features of donor liver blood vessels in laparoscopic left lateral donor liver acquisition and their clinical significance.Methods:The retrospective and descriptive study was conducted. The clinical data of 39 living donor liver transplantation (LDLT) donors who were admitted to Huashan Hospital Affiliated to Fudan University between October 2016 and December 2018 were collected. There were 10 males and 29 females, aged (31±7)years. The clinical data of 39 LDLT recipients were collected. There were 26 males and 13 females, aged 8 months (range, 4-68 months). Abdominal enhanced computed tomography and three-dimensional vascular reconstruction were performed on donors to evaluate the anatomical characteristics of hepatic vessels. All the donors underwent laparoscopic left lateral donor liver acquisition. Observation indicators: (1) three-dimensional vascular reconstruction of preoperative imaging; (2) surgical conditions; (3) follow-up. Follow-up was performed using outpatient examination to detect complications of recipients after LDLT up to October 2019. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were represented as M (range). Count data were expressed as absolute numbers or percentages. Results:(1) Three-dimensional vascular reconstruction of preoperative imaging: the anatomical characteristics of hepatic artery and hepatic vein revealed by three-dimensional vascular reconstruction of preoperative imaging of 39 donors included ① middle hepatic artery was present in 11 donors, among which 5 started from the right hepatic artery, 3 from the confluence of the right and left hepatic artery, and 3 from the left hepatic artery. Two donors had anatomical variation in the left hepatic artery which was presentation of left accessory hepatic artery originated from the left gastric artery. The other 26 donors had no middle hepatic artery or anatomical variation in the left hepatic artery. ② The left hepatic vein and the middle hepatic vein of 9 donors were respectively drained into the inferior vena cava. Seven donors had the left upper branch of the left hepatic vein, and 23 donors had a joint trunk of the left hepatic vein and the middle hepatic vein which drained into the inferior vena cava. (2) Surgical conditions: ① all the 39 donors successfully underwent laparoscopic left lateral donor liver acquisition. The operation time and volume of intraoperative blood loss were (160±32)minutes and (142±74)mL. ② Of 11 donors with middle hepatic artery, left hepatic artery was the dominant artery in 8 donors and was used for hepatic artery anastomosis and reconstruction in liver transplantation, middle hepatic artery started from left hepatic artery in 3 donors and the joint trunk of left and middle hepatic artery was used for hepatic artery anastomosis and reconstruction in liver transplantation. Of 2 donors with anatomical variation in the left hepatic artery, one had left accessory hepatic artery as the dominant artery and the other had left hepatic artery as the dominant artery. Left accessory hepatic artery and left hepatic artery were respectively used for hepatic artery anastomosis and reconstruction in liver transplantation. The other 26 donors had left hepatic artery for hepatic artery anastomosis and reconstruction in liver transplantation. ③ Among the 39 donors, 11 received intraoperative left hepatic vein preferred approach and 28 received intraoperative non-left hepatic vein preferred approach. The operation time and volume of intraoperative blood loss of donors with left hepatic vein preferred approach were (147±22)minutes and (110±44)mL, respectively, versus (169±33)minutes and (154±81)mL of donors with non-left hepatic vein preferred approach, showing significant differences in the above indicators between the two groups ( t=4.19, 2.81, P<0.05). (3) Follow-up: 39 donors were followed up for 10 months. During the follow-up, there was no hepatic artery anastomotic bleeding, stenosis, ischemic bile duct injury and biliary stenosis caused by poor hepatic arterial blood supply, or any complications related to hepatic venous outflow tract stenosis. Conclusions:Three-dimensional vascular reconstruction before laparoscopic left lateral donor liver acquisition can reveal the anatomical variation of middle hepatic artery and left hepatic artery, which can guide the selection of surgical approach. The left hepatic vein preferred approach is recommended for the qualified donor in the laparoscopic left lateral donor liver acquisition, which can shorten the operation time and reduce the volume of intraoperative blood loss.
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Objective To summarize the screening Methods for human parvovirus (HPV) B19 infection after liver transplantation and analyze the related risk factors. Methods Clinical data of 86 recipients were retrospectively analyzed. According to the Results of next generation sequencing (NGS), all recipients were divided into the HPV B19 infection group and control group. Clinical characteristics, treatment regime and clinical prognosis of patients infected with HPV B19 were analyzed. The risk factors of HPV B19 infection were analyzed using univariate and multivariate Logistic regression model by forward LR step method. Results Nine of the 86 recipients developed fever and progressive anemia with unexplained reasons at approximately 2 weeks after liver transplantation. NGS detection demonstrated that HPV B19 was positive and they were diagnosed with pure red cell aplasia (PRCA) caused by HPV B19 infection. After intravenous immunoglobulins (IVIG) was given and the immunosuppressant therapy was adjusted, the hemoglobin levels in all patients were significantly increased. The Results of multivariate analysis revealed that low serum globulin level in peripheral blood at postoperative 7 d [odds ratio (OR) =0.749, P=0.040] and young age (OR=0.937, P=0.038) were the independent risk factors of HPV B19 infection after liver transplantation. Conclusions HPV B19 infection should be considered in relatively young patients with unexplained hemoglobin decline early after liver transplantation. NGS screening is an effective method for early diagnosis of HPV B19 infection. Low serum globulin level in peripheral blood at postoperative 7 d and young age may be independent risk factors of the incidence of HPV B19 infection.
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Objective@#To explore the clinical efficacies of applying aged marginal donor liver.@*Methods@#From January 2015 to June 2018, clinical data were retrospectively analyzed for 199 adult liver transplantation donors and recipients. They were divided into two groups of aged (≥60 years) and appropriate age (<60 years). The prognosis of two groups was compared after a follow-up period of 1 year. And the aged group was further assigned into lower and higher fat infiltration groups according to the degree of fat infiltration in donor liver and compared the prognosis of two groups.@*Results@#No significant differences existed in initial, peak value and recovery time of transaminase (AST/ALT), peak value and recovery time of total bilirubin, glutamyl transpeptidase, alkaline phosphatase, international normalized ratio (INR), peak value of lactate, postoperative hospital stay, graft dysfunction, biliary/vascular complications, acute/chronic rejection or graft survival rate between aged and appropriate age groups post-transplantation. The aged group was further divided into lower and higher fat infiltration groups according to the fat infiltration rate (<20%, ≥20%). And significant inter-group differences existed in peak value and recovery time of AST/ALT, peak value of total bilirubin, glutamyl transpeptidase, lactate, postoperative hospital stay and graft dysfunction. The above parameters were significantly worse in higher fat infiltration group. Also the rejection rate was higher in high group at 1 year post-operation and no significant inter-group difference existed in biliary/vascular complications. In higher group, 4 patients showed graft dysfunctions during perioperative period. Two of them were discharged successfully after secondary transplantation and another 2 patients died.@*Conclusions@#On the premise of comprehensive evaluations of donor liver status and reasonable matching of recipients, aged marginal donor liver can be safely applied with excellent clinical outcomes. Severe fatty donor liver should be employed with caution. Hypertensive drugs, high serum sodium and long period of cold ischemia are also important influencing factors for aged donors.
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Objective To explore the clinical efficacies of applying aged marginal donor liver . Methods From January 2015 to June 2018 ,clinical data were retrospectively analyzed for 199 adult liver transplantation donors and recipients .They were divided into two groups of aged (≥60 years) and appropriate age (<60 years) .The prognosis of two groups was compared after a follow-up period of 1 year .And the aged group was further assigned into lower and higher fat infiltration groups according to the degree of fat infiltration in donor liver and compared the prognosis of two groups . Results No significant differences existed in initial ,peak value and recovery time of transaminase (AST/ALT ) , peak value and recovery time of total bilirubin , glutamyl transpeptidase , alkaline phosphatase ,international normalized ratio (INR) ,peak value of lactate ,postoperative hospital stay , graft dysfunction , biliary/vascular complications , acute/chronic rejection or graft survival rate between aged and appropriate age groups post-transplantation .The aged group was further divided into lower and higher fat infiltration groups according to the fat infiltration rate (< 20％ ,≥20％ ) . And significant inter-group differences existed in peak value and recovery time of AST /ALT ,peak value of total bilirubin , glutamyl transpeptidase , lactate , postoperative hospital stay and graft dysfunction .The above parameters were significantly worse in higher fat infiltration group .Also the rejection rate was higher in high group at 1 year post-operation and no significant inter-group difference existed in biliary/vascular complications . In higher group , 4 patients showed graft dysfunctions during perioperative period .Two of them were discharged successfully after secondary transplantation and another 2 patients died .Conclusions On the premise of comprehensive evaluations of donor liver status and reasonable matching of recipients ,aged marginal donor liver can be safely applied with excellent clinical outcomes .Severe fatty donor liver should be employed with caution . Hypertensive drugs ,high serum sodium and long period of cold ischemia are also important influencing factors for aged donors .
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Objective To explore the clinical features and risk factors associated with intrahepatic and hilar cholangiocarcinoma after liver transplantation .Methods Retrospective analysis of clinical data was performed for 20 hospitalized patients with intrahepatic and hilar cholangiocarcinoma from June 25 ,2014 to October 31 ,2018 .Treatments and follow-up outcomes were analyzed .The survival rate was calculated by the Kaplan-Meier method and the survival curve plotted .Cox regression model was employed for analyzing the prognostic factors .Results The cumulative recurrence rate of patients with AJCC stage Ⅰ /Ⅱ was significantly lower than that in AJCC stage Ⅲ/Ⅳ .And the cumulative recurrence rate of stageⅠ/Ⅱ Patients was 0 and that of stage Ⅲ/Ⅳ 76％ (P=0 .042) .Cox regression model showed that CA19-9 was the only prognostic factor .An elevated level of CA19-9 was associated with high recurrence post-transplantation (HR=1 .001;95％ CI:1 .000～1 .001;P=0 .035) .Conclusions During progressive stage ,the recurrence rate is higher with a worse prognosis .And an elevation of CA19-9 is an independent poor prognostic factor after intrahepatic and hilar cholangiocarcinoma transplantation .
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Objective To investigate the clinical efficacy and therapeutic progress of orthotopic liver transplantation for the treatment of hepatic epithelioid hemangioendotheliom(a EHE). Methods Clinical data of 2 patients diagnosed with hepatic EHE were retrospectively analyzed. One patien(t case 1) was diagnosed with multiple hepatic EHE complicated with multiple infarction lesions of the spleen, and underwent orthotopic liver transplantation combined with splenectomy. The other cas(e case 2) was diagnosed with multiple hepatic EHE and received orthotopci liver transplantation alone. Literature review was performed. Pathological characteristics, clinical efficacy of liver transplantation and clinical prognosis of hepatic EHE patients were analyzed. Results Two patients successfully underwent surgery and were discharged postoperatively. The diagnosis of hepatic EHE was confirmed by pathological examinaiton and case 1 was complicated with EHE of the spleen . For case 1, tacrolimus was replaced by sirolimus at postoperavtie 1 month. At postoperative 4 months, capecitabine was orall y administered( chemotherapy) for EHE recurrence. At 6 months after surgery, the patient wa sdiagnosed with recurrent hepatic EHE complicated with multiple bone metastases, and waso rally administered with sorafenib. At postoperative 7 months, the patient died from cachexia and liver failure. Case 2 was followed up until the submission date( 8 months after surgery). No postoperative complications and tumor recurrence were observed. Previous studies had demonstrated that surgical resection was the primary therapy of hepatic EHE. Liver transplantation was highly recommended for patients with multiple unresectable hepatic EHE and extra-hepatic lesions. Moreover, chemotherapy, percutaneous puncture combined with transcatheter arterial chemoembolization and anti-angiogenesis treatment exerted certain clinical efficacy.C onclusions Surgical resection remains the primary therapy of hepatic EHE. For patients with multiple intrahepatic EHE, liver transplantation is considered as the optimal treatment. Much attention should be diverted to the prevention and treatment o f recurrent hepatic EHE following liver transplantation, aiming to improve the clinical efficacy.
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Objective To explore the feasibility of lithium heparin anticoagulant plasma instead of serum in biochemical test . Methods 54 biochemical indexes were comparatively detected in 100 samples of lithium heparin anticoagulant plasma and serum . Results The detection results of 45 biochemical indexes in 100 samples of lithium heparin anticoagulant blood plasma and serum showed no statistically significant differences (P>0 .05) .There were statistically significant differences in the indexes of total pro-tein(TP) ,potassium ion(K+ ) ,lactic dehydrogenase(LDH) ,glucose(GLU) ,creatine kinase-MB(CK-MB) and lipase(LPS) between lithium heparin anticoagulant plasma and serum(P<0 .05) ,while results showed good correlation(the maximum r value was 0 .998 , the minimum r value was 0 .887);3 indexes of transferrin(TRF) ,α-L-fucosidase(AFU) and leucine aminopeptidase (LAP) had statistically significant differences (P<0 .05) and showed no correlation(r<0 .6) .Conclusion Lithium heparin has the strongly an-ticoagulant ability with the advantages of non-influence on cell volume and no hemolysis ,which can be used for routine biochemical test ,especially suitable for the outpatient service ,emergency and the patients with blood coagulation dysfunction ,but the detection of TRF ,AFU and LAP can not be suitable .
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Objective To investigate some improvements in the surgical techniques of adult-to-adult living donor liver transplantation( A-A LDLT) without the middle hepatic vein(MHV) for hepat-ic vein reconstruction. Methods The retrospective analysis was made on the clinical data of 11 recipi-ents who underwent the operation in A-A LDLT including the hepatic vein reconstructed in right liver lobe without MHV from June 2007 to January 2008. The key techniques included reconstructing out-flow of graft on shaping the tips of vena cava and right hepatic veins, cadaveric vein allografts stored in 4℃ UW solution within 7d being used for significant-sized hepatic vein reconstruction such as tributa-ries of the middle hepatic vein from V5, V8 and right inferior hepatic vein. Results 10 cases success-fully underwent reconstruction of outflow of graft on shaping the tips of vena cava and right hepatic veins and the outflow reconstruction ratio of V5, V8 and right inferior hepatic vein was 81. 8% (9/11), 7 one-vein reconstruction, 1 two-vein reconstruction and 1 three-vein reconstruction. 1 recipient died of renal failure and pulmonary infection 14 days after operation without venous outflow obstruc-tion. Doppler ultrasonography showed no thrombosis and the blood flowed smoothly in the right he-patic vein of other 8 recipients during the 9th to 15th mouth of follow-up. The cumulative patency rates of these 8 survivals for interposition vein grafts were 100% (11/11), 72. 7 %(8/11), 54. 5%(6/11) and 36. 5%(4/11) in 1, 3, 6 and 9 mouths, respectively. The regeneration of paramedian sectors was equivalent. Conclusion Shaping the tips of vena cava and right hepatic veins and using cadaveric vein allografts in adult-to-adult right lobe living donor liver transplantation for hepatic vein reconstruc-tion are both safe,simple and effective methods.This approach can be recommended.