Objective To evaluate the effectiveness and safety of calcineurin inhibitor (CNI) withdrawal from target-of-rapamycin-inhibitor(TOR-I)-based immunosuppression in kidney transplant recipients. Methods We searched MEDLINE, EMbase, SCI, CBM and The Cochrane Library to screen randomized controlled trials (RCT) of calcineurin inhibitor (CNI) withdrawal from target-of-rapamycin-inhibitor-(TOR-I)-based immunosuppression in kidney transplant recipients. The search was updated in Semptember 2009. The quality of the included trials was assessed. RevMan 5.0 software was used for meta-analyses. Results A total of 14 reports from 10 RCTs were identified. Five RCTs were graded A and five graded B. The meta-analyses indicated: RR (95%CI) values of the 1, 2, 4-year acute rejection rates were 1.64 (1.19, 2.27), 1.53 (1.06, 2.22) and 1.21 (0.73, 1.98), respectively; RD (95%CI) values of 1, 2, 4-year patient survival rates were – 0.01 (– 0.02, 0.01), – 0.00 (– 0.03, 0.02) and 0.03 (– 0.01, 0.08), respectively; RD (95%CI) values of 1, 2, 4-year graft survival rates were 0.00 (– 0.02, 0.02), 0.00 (– 0.03, 0.04) and 0.07 (0.01, 0.12), respectively; and glomerular filtration rate WMD was 9.50 and 95%CI 2.96 to 16.03. Conclusion Based on the current evidence, compared to CNI, CNI withdrawal from sirolimus-based immunosuppression in kidney transplantation could be advantageous for renal function. One-year acute rejection rate and 4-year graft survival rate increase. One-year patient/graft survival and fouryear acute rejection rate remain virtually unvariable. The long-term results need further confirmation.
Objective We aimed to investigate the attitude and suggestion from doctors, pharmacists and civil servants concerning brain death and organ transplantation and the legislation. Methods A questionnaire with 10 sections and 44 questions was designed and distributed. The effective questionnaire data was then recorded and checked for descriptive analysis. Results In 1 400 questionnaires distributed, 1 063 were responded and 969 of them were valid and analyzed. The respondents showed an incomplete understanding of brain death and organ transplantation laws. Seventy-four percent of the respondents recognized and accepted the standard of brain death. They agreed that legislation should be involved in the removal of organs for transplantation, the future use of the organs, and insurance and compensation for the donor for possible health risks induced by organ removal. Of the 969 respondents, 92% considered it necessary to have legislation in brain death and organ transplantation, and 61% thought that it is time to legislate. Conclusion Legislation for brain death and organ transplantation is urgent and timely in China. The laws must include the respective rights and obligations of patients, close relatives, and medical institutions. Educating the public about brain death and organ transplantation should also be encouraged in a variety of ways.
Objective To establish different kinds of reduced size liver transplantation model of rats， and to explorethe optimal marginal size of liver graft in orthotopic liver transplantation， in purpose of providing a kind of animal modelfor the study about mechanism and prevention measures of small-for-size syndrome. Methods One hundred and ninety-two rats were randomly divided into whole liver graft transplantation group （underwent whole liver graft transplantation），half liver graft transplantation group （the median lobe and right lobe of the liver were selected to be the graft）， small size liver graft transplantation group （the median lobe of the liver was selected to be the graft）， and extra-small size liver graft transplantation group （the median lobe and left lobe of the liver were reduced， and remained lobes were selected to be the graft）， each group enrolled 48 rats. After liver graft transplantation， 24 rats of each group were selected to observe the survival situation， 12 rats of each group were selected to measure portal venous pressure at time point of before operation，and 5， 15， 30， 45， and 60 minutes after transplantation. The other 12 rats of each group were test the level of alanine aminotransferase （ALT）. Results Seven-day survival rate of the whole liver graft transplantation group， half liver graft transplantation group， small size liver graft transplantation group， and extra-small size liver graft transplantation group was 100% （24/24）， 87.5% （21/24）， 37.5% （9/24）， and 0 respectively. Portal venous pressure of whole liver graft trans-plantation group was stable after opening the portal vein， although there was slight increase at prophase in half liver graft transplantation group， and then the portal venous pressure would let down， keeping stable at the later stage. But in small size liver graft transplantation group and extra-small size liver graft transplantation group， the portal venous pressure incr-eased and got the top at 15 minutes after opening the portal vein， and then induced， keeping stable during the 45-60 minutes.Portal venous pressure at the point of 5 （r=-0.942）， 15 （r=-0.947）， 30 （r=-0.900）， 45 （r=-0.825）， and 60 （r=-0.705）minutes after opening the portal vein were significantly related to liver graft size （P＜0.001）. The levels of ALT in wholeliver graft transplantation group and half liver graft transplantation group were both lower than those of small size livergraft transplantation group and extra-small size liver graft transplantation group （P＜0.05）， and levels of ALT in small size liver graft transplantation group was lower than extra-small size liver graft transplantation group too （P＜0.05）. Levelof ALT at 24 hours after transplantation were significantly related to liver graft size （r=-0.685， P＜0.001）. Conclusions The minimum graft volume/standard liver volume （GV/SLV） in reduced size liver transplantation in rat is 50%. The liver graft whose GV/SLV is 30%-35% should be considered as marginal size liver graft， and the liver graft whose GV/SLV less than 30% should be considered as extra-small size liver graft in the rat.
Objective To approach the prognosis after liver transplantation （LT） of liver function for Child grade A in patients with portal hypertension， and to compare with periesophagogastric devascularization with splenectomy （PDS）. Methods The data of 195 portal hypertension cases with Child A caused by hepatitis B cirrhosis who received surgical treatment of PDS （152 cases） or LT （43 cases） in division of liver transplantation center of West China Hospital of Sichuan University from 1999 to 2011 were retrospectively analyzed. The pre-， intra-， and postoperative variables in two groups that including patients’ age， score of Child， score of model for end-stage liver disease （MELD）， total bilirubin （TB），creatinine （Cr）， international normalized ratio （INR）， albumin （Alb）， complications of portal hypertension， amount of intraoperative bleeding and blood transfusion， operative time， and in the ICU and hospital stay time were compared. The postoperative outcomes were statistically analyzed including severe postoperative complications， short-term and long-term survival rates. Results Compared with PDS group， the amount of intraoperative bleeding and blood transfusion of LT group were morer （P＜0.05）， the operative time， in the ICU and hospital stay time of LT group were longer （P＜0.05）. The rate of severe postoperative complications in LT group was higher than that in PDS group 〔18.60% （8/43） vs. 1.97% （3/152），P＜0.05〕. The levels of TB and Cr during the postoperative period in LT group were higher than that in PDS group （P＜0.05）. Although the INR on day 1 after operation in LT group was higher than that in PDS group （P＜0.01）， but the difference disappeared soon on day 7 after operation in two groups （P＞0.05）.The 1-， 3-， and 5-year survival rates of the LT and PDS groups were 90.3%， 86.5%， 86.5%， and 100%， 100%， 100%， respectively， significant difference were observed in both short-term and long-term survival rates between the two groups （P＜0.05）. Conclusion LT offered no significant survival benefit to patients with portal hypertension and Child A due to hepatitis B cirrhosis， whereas PDS could be an effective treatment.
Objective To explore the feasibility and safety of liver transplantation （LT） in treatment of upper gastrointestinal hemorrhage in patients with portal hypertension， and to compare the therapeutic effects with conventional operation （CO）. Methods The clinical data of 303 patients with bleeding portal hypertension from Feb. 2009 to Feb. 2012 in the department of hepatobiliary and pancreatic surgery of First Affiliated Hospital of Zhejiang University were retrospectively analyzed. One hundred and one patients received LT procedure （LT group）， whereas the other 202 patients received CO procedure （CO group）. Postoperative follow-up period was 8-44 months （average 26 months）. Results Liver function before operation in CO group was significantly better than that in LT group（P＜0.01）. The mortality of CO group and LT group were 7.4%（14/189） and 3.0%（3/101， P=1.00）， respectively. The rebleeding rate of patients underwent LT was 2.0%（2/101）， significantly lower than that of CO group 〔9.5%（18/189）， P＜0.05〕. The vanish rate of esophagogastric varice in patients underwent LT was 86.1%（87/101）， significantly lower than that of CO group 〔54.5%（86/189）， P＜0.01〕. Conclusions LT treatment for bleeding portal hypertension is feasible and safe. Patients with good liver function despite hemorrhage history may be managed satisfactorily with conventional surgery. LT is the only curative treatment for patients with portal hypertension in end-stage liver disease.
Objective To summarize the research progress of xenotransplantation.Methods Domestic and international publications about xenotransplantation were summarized and reviewed. Results Hyperacute xenograft rejection was a huge problem for xenotransplantation， but it could be alleviated if the organs or tissues of donor were genetically modified. So far the graft survival time differed greatly due to characteristics of different organ. Conclusions By reviewing the studies of relevant papers about xenotransplantation， a comprehensive understanding of research background and a suitable research direction of xenotransplantation can be supplied. The graft organs or tissues from genetically modified donors are expected to avoid or alleviate hyperacute xenograft rejection.
Objective To observe the dynamic histopathologic changes of acute rejection in rat orthotopic liver transplantation (OLT) model after tacrolimus discontinued and provide some prediction and evaluation data for clinical acute rejection after liver transplantation. Methods Kamada two-cuff technique was used to establish 60 rat OLT model， and male DA rats, male Lewis rats were used as donors and recipients respectively. Therapeutic amount of tacrolimus (0.05 mg/kg, twice per day, continued for 8 d, 1 d before operation and 7 d after operation, intragastric administrated) was administrated to recipients, then continuously half dose was decreased every day beginning from day 8 after operation and tacrolimus administration was stopped on day 13. Liver tissues were collected on day 7, 14, 21, and 28 after liver transplantation. Histopathologic changes and rejection activity index (RAI) of liver tissues were observed, survival time of recipients was calculated. Results Owing to protection effects of tacrolimus, liver tissues displayed no significant histopathologic changes of acute rejection in 7 d after OLT, while typical acute rejection histopathologic changes began to be observed on day 14 after OLT due to tacrolimus discontinuation. On day 14, 21, and 28, RAI were 3.7±0.9, 6.3±0.9, and 8.1±0.7 respectively. Survival time of recipients was (20.85±0.71) d with a median of 21 d. Conclusion Acute rejection could be induced in rat OLT model after tacrolimus discontinuation, and data collected from this model shows some extent of predictive value and assessment value for clinical liver acute rejection.
ObjectiveTo determine the risk factors for recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). MethodsThe clinical data from seventysix consecutive HCC patients who underwent OLT were retrospectively analyzed. The patients were divided into nonrecurrence group (n=53) and recurrence group (n=23) based on recurrence, and the characteristics of tumor recurrence were analyzed. ResultsThe overall recurrence rate of tumor was 30.3% (23/76). By univariate analysis, gender (P=0.449), age (P=0.091), received preoperative therapy or not (P=0.958), tumor numbers (P=0.212), and HBV/HCV infection (P=0.220) were not closely related with tumor recurrence, while the integrality of tumor capsule (P=0.009), tumor stage (P=0.002), tumor diameter (Plt;0.001), vascular invasion (Plt;0.001), and AFP level before transplantation (P=0.044) were significantly related with tumor recurrence. Furthermore, the oneyear recurrence rate of tumor was higher in patients whose AFP level returned to normal within two months after transplantation (Plt;0.001) and tumor diameter was less than 5.0 cm (P=0.001). Multivariate analysis revealed that tumor diameter (P=0.001, OR=6.456, 95%CI: 2.356-17.680), vascular invasion (P=0.030, OR=10.653, 95%CI: 1.248-90.910), and AFP level before transplantation (P=0.017, OR=2.601, 95%CI: 2.196-5.658) were independent risk factors for tumor recurrence. ConclusionMore attentions shall be paid to these patients with tumor diameter gt;5.0 cm, vascular invasion, and AFP level before transplantation ≥400 μg/L, in particular AFP level is beyond normal within two months after transplantation, and antitumor therapy shall be given as soon as possible.
Objective To study the mechanism of immune hyporesponsiveness of allograft rejection induced by transfusion nonpufsed allopeptide syngeneic immature dendritic cell (imDC) generated from recipient bone marrow progenitors and to explore a possible strategy for liver allograft protection in clinic. Methods Forty experimental rats were randomly divided into 4 group: control group, cyclosporine A (CsA) group, mature DC (mDC) group and imDC group. In control group, Wistar rats only received liver transplantation. In CsA group, Wistar rats underwent liver transplantation plus CsA treatment 〔10 mg/（kg·d)〕. In mDC group, recipient-derived mDC 1×106 were infused intravenously through the penile vein to Wistar rats. In imDC group, ImDC with the dose of 1×106 were injected into Wistar rats via the dorsum vein of penile. In each group, five recipients were killed on the 10th day after transplantation, the other five recipients were left to observe survival time. The levels of ALT, AST, TBIL, IL-2, IFN-γ, IL-4 and IL-10 were detected. The acute rejection and the expression of FasL/Fas in the grafts were detected by HE and immunohistochemical staining. Western blot was used to detect Scurfin protein expression of CD4+ CD25+ T cells. Results The median survival time of the liver allografts in CsA group and imDC group were significantly longer than that in control group and mDC group ( P ＜ 0.05). The levels of ALT and TBIL in control group and mDC group were significantly higher than those in CsA group and imDC group ( P ＜ 0.05). Compared with CsA group and imDC group, the levels of IL-2 and IFN-γ were higher but the levels of IL-4 and IL-10 were lower in control group and mDC group ( P ＜ 0.01). Slightly or no rejection reaction was found in CsA group and imDC group ( P ＜ 0.05). The Scurfin protein expressions of CD4+ CD25+ T cells of imDC group were significantly higher than those of other three groups. Conclusion Application of nonpufsed allopeptide syngeneic recipient-derived imDC is an effective way to induce immune hyporesponsiveness by blocking indirect recognition in rat liver transplantation model. Survival span is significantly prolonged by its protective effect. The mechanism of immune hyporesponsiveness induced by imDC transfusion might be involved in some aspects: T cell apoptosis, immune deviation of Thl/Th2 cytokine net and inhibition of T lymphocytes responsiveness by regulatory T cells.
Objective To investigate the effect of constitutively active Akt1 gene on rat engrafted islets in apoptosis and revascularization, and to explore potential method of gene therapy in the islet transplantation. Methods Rat islet which was transfected constitutively actived Akt1 gene via adenovirus vector using MOI=500. Thirty-six streptozotocin induced diabetic Wistar rats were divided into 3 groups complete randomly: Adv-CA-Akt1 group, Adv-LacZ group and simple transplantation group. Blood glucose and insulin were determined after operation. TUNEL was used to detect the apoptotic islet cells. HE and immunohistochemical staining of insulin were used to evaluate the histology of the islet grafts. The microvessel density (MVD) was determined by CD31 immunohistochemical staining. Results The fasting glucose level in Adv-CA-Akt1 group restored to normal 2 days after transplantation. However, in Adv-LacZ group and simple transplantation group, it reduced but still kept being hyperglycemia. And the serum insulin level was higher than other two groups ( P ＜ 0.05). Compared to simple transplantation group and Adv-LacZ group, apoptotic rate decreased 25% in Adv-CA-Akt1 group, a large number of islet grafts were seen under the capsule of the kidney, which were positively stained by insulin antibody. In the other two groups, the islet groups mass were lighter, and few positively stained by insulin antibody. MVD showed lighter positive endothelial cells stained by CD31 antibody in the other two groups than Adv-CA-Akt1 group ( P ＜ 0.05). Conclusion Constitutively activate Akt1 gene can prolong graft survival during early posttransplant period, and can accelerate the revascularization of islet grafts effectively.