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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 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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Tumors are not isolated structures within organisms. Tumor tissue innervation has been confirmed, and neurotransmitters can directly regulate proliferation, angiogenesis, invasion and metastasis of tumors through acting on kinds of receptors on tumor cells, meanwhile, through acting on receptors on immune cells. Neurotransmitters can modulate differentiation, proliferation and activation of immune cells and influence tumor immune response. Correspondingly, cytokines released from tumor cells stimulate afferent sensory fibers or traverse blood-brain barrier, and affect the activities of central nervous system. Psychosociological stress can influence sympathetic system or hypothalamic-pituitary-adrenal axis, and cause variation of the levels of catecholamines and brain-derived neurotrophic factor (BDNF), which may affect initiation and progression of tumors. Based on the potential role of neuromodulation in initiation and progression of tumors, intervention targeting nervous system would be a promising strategy in systemic intervention of tumors.
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Objective To investigate the expression of P21ras and PIK3CA proteins in hepatitis B virus-related hepatocellular carcinoma(HBV-HCC), post-hepatitis B hepatic cirrhosis (HBV-hepatic cirrhosis)and normal hepatic tissues specimen, and their correlation between HBV-HCC and HBV-hepatic cirrhosis tissues.Methods Using immunohistochemistry, the expression of P21ras and PIK3CA proteins in 34 cases of HBV-HCC, 37 cases of HBV-hepatic cirrhosis and 30 cases of normal liver tissues specimen were detected and compared. Results The mean gray scales of P21ras protein in HBV-HCC, HBV-hepatic cirrhosis and normal hepatic tissue specimen were 138.86 ± 2.9, 145. 34 ± 2.06 and 152.07 ± 1.17 (P ＜ 0. 0l), respectively, and were related to the progression of hepatopathy (P ＜0.01). The mean gray scales of PIK3CA protein in HBV-HCC, HBV-hepatic cirrhosis and normal hepatic tissue specimen were 138.20 ± 3. 14, 149.49 ±0. 78 and 154.71 ± 1.29 (P ＜ 0.01), respectively, and were related to the progression of hepatopathy (P ＜ 0. 01).There were apparent correlation between P21ras and PIK3CA in HBV-HCC and HBV-hepatic cirrhosis respectively (r =0. 64, P ＜0. 05; r =0. 42, P ＜0. 05). Conclusion The overexpression of P21ras and PIK3CA in HCC and hepatic cirrhosis tissue suggests that they participate in the tumorigenesis and development of hepatocellular carcinoma and hepatic cirrhosis, and there may be a signal transduction pathway of P21ras-PI3K in HBV-HCC and HBV-hepatic cirrhosis.
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Objective To investigate the frequency distribution of Val762Ala(T2444C)polymorphism among Han Chinese population in Gansu province,and to explore its relation to the suseeptibihty to gastric cancer. Methods A hospital-based,case-control study was performed involving 138 patients with gastric cancer and 110 healthy controls by PCR-RFLP method.Logistic regression and Chisquare analyses were used to assess OR and 95% CI. Results PARP-1762Ala allele was overexpressed in gastric cancer cases(11.5%)compared with controls(4.5%)(OR=3.012,95%CI 1.054-8.603,P=0.033).Statistic analysis showed increaged risk for gastric cancer patients with the 762Ala allele.Conclusion PARP-1 Val762Ala(T2444C)is related to the risk of gastric cancer,PARP-1762Ala allele could be used as a susceptibility marker for the development of gastric cancer.