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"Re-evaluation of ""Shanghai Criteria"": indication of liver transplantation for hepatocellular carcinoma"

Chinese Journal of Organ Transplantation.2013;34(9):521-523. doi:10.3760/cma.j.issn.0254-1785.2013.09.003

Objective To reevaluate Shanghai Criteria of liver transplantation (LT) for hepatocellular carcinoma (HCC).Method We evaluated the outcome of 433 consecutive patients with HCC who underwent LT from 2001 to 2013 at Zhong shan Hospital,Fudan University.The Kaplan Meier product-limit method with log rank test was used to evaluate survival rate according to different Criteria.Result The 5-year overall survival (OS) rate and relapse-free survival (RFS) rate were as follows:Milan Criteria (n =169; 72.5％ and 79.0％),UCSF Criteria (n =223; 68.2％ and 75.7％) ;Shanghai Criteria (n =255; 65.9％ and 70.6％) ; Pittsburgh Criteria (n =419,55.6％ and 61.2％).There was no significant difference in the 5 year OS and RFS between Shanghai Criteria group and Milan Criteria group (P＞0.05).Conclusion Shanghai Criteria,which modestly expanded current criteria while still preserving similar long term survival,could be more fit for the situation of China.

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Clinical diagnosis and surgical management of ureteral obstruction after renal transplantation

Qing ZHANG ; Zexuan SU ; Jie CHEN ; Hongwen DING ; Yifan LIU ; Xinghua DOU ; Liping SHI

Chinese Journal of Organ Transplantation.2013;34(9):542-544. doi:10.3760/cma.j.issn.0254-1785.2013.09.008

Objective To investigate the diagnosis and surgical management of ureteral obstruction after renal transplantation.Method A respective study was performed on 15 cases of ureteral obstruction who received renal allografts.All of the cases were confirmed,including 5 cases of stenosis of ureterovesical junction,4 cases of stenosis of distal ureter,2 cases of blood clot blockage,2 cases of edema due to perforation of distal ureter,1 case of ureteral calculi,and 1 case of extrinsic compression of hematoma.All 14 patients underwent open surgical management to reestablish ureter with D-J catheter as stent for 12-16 weeks.One patient was subjected to percutaneous nephrostomy followed by percutaneous ureteroscopy,the obstructed site was identified at ureterovesical junction and antegrade balloon dilation and D-J stent in ureter were performed subsequently.Result Fifteen patients were diagnosed as ureteral obstruction by colour Doppler ultrasound and MRU.All of the patients were resolved the obstructions after surgical managements and the renal function got improved.No reobstruction occured during one year follow-up period.Conclusion Colour Doppler ultrasound and MRU can definitely be used to diagnose ureteral obstruction after renal transplantation.Early diagnosis and surgical management are very important.Open surgical management of the obstructed ureter is an effective method.Antigrade balloon dilation is a therapeutic approach to treat ureteral obstruction.

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Role of toll-like receptor signaling in skin transplantation responses in mice

Chao LI ; Xia HUANG ; Tao YANG ; Limin ZHANG ; Mingqiang LI ; Ping ZHOU

Chinese Journal of Organ Transplantation.2013;34(9):550-553. doi:10.3760/cma.j.issn.0254-1785.2013.09.010

Objective To investigate the essential role of Toll-like receptor (TLR) signaling in dendritic cells in rejection responses of skin transplantation in mice.Method Immature wild-type BALB/c bone marrow dentritic cells (BMDCs) were stimulated by a TLR agonist,CpG,in the presence of ST2825,an inhibitor of key molecule myeloid differentiation factor 88 (MyD88) in TLR signal transduction,or in the absence for 24 h in vitro.Co-stimulatory molecules CD80 and CD86 were analyzed by flow cytometry.Wild-type C57BL/6 na ve T cells stained with CFSE,a fluorescent dye,were co-cultured with BALB/c DCs for 3 days in the presence or absence of ST2825.CD3 +/CFSE+cells were analyzed by flow cytometry.Minor antigen-mismatched (HY-mismatched) skin allograft model was employed in this study in which the donors were all males and the recipients were all females.The experimental groups were divided as follows:the control group,the donors and the recipients were all wide type BALB/c mice; the MyD88 group,the donors and the recipients were all MyD88-konckout BALB/c mice; the DCs group,the donors and the recipients were all MyD88-knockout BALB/c mice and the recipients were transfused with donor-sourced DCs after transplantation; the experimental group,the donors and the recipients were all MyD88-knockout BALB/c mice and the recipients were transfused with donor-sourced DCs pre-treated with ST2825after transplantation.The survival time of skin allografts was observed.Result ST2825 could dose dependently inhibit the high level expression of co-stimulatory molecules CD80 and CD86 induced with CpG.Similarly,and it could also dosedependently inhibit the allo-reactive T cell proliferation upon the stimulation with DCs.The survival time of every group was as follows:the control group (22.8 ±2.8) days vs.the MyD88 group (＞100 days) vs.the DCs group (9.7± 2) days vs.the experimental group (＞100 days,P＜0.05,vs.the DC group).Conclusion DCs may play an essential role in rejection responses of transplantation via TLR signaling.The inhibitor of TLR signaling,ST2825,could inhibit the activation of DCs and the biological functions,which might be contributed to the inhibitory effects of ST2825 on DCs maturation and indirect suppression on the proliferation of allo reactive T cells.

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Involvement of miR-338-5p in antibody-mediated renal allograft rejection by targeting TRAF3

Haiyan XU ; Xiaozhou HE ; Xuyi MA ; Dong XUE ; Yanyun ZHANG ; Xueguang ZHANG

Chinese Journal of Organ Transplantation.2013;34(9):554-558. doi:10.3760/cma.j.issn.0254-1785.2013.09.011

Objective To explore the significantly differentially.expressed microRNAs during antibody-mediated renal allograft rejection.Method MicroRNA array assay was used,and the obtained data were analyzed by bioinformatics analysis.The obtained significant microRNAs were further analyzed to forecast the targeted genes in the common database,then experimental means were used to testify the targeted genes.Result During the antibody-mediated renal allograft rejection,the significantly over-expressed microRNAs were miR-200c,miR-200b,miR-30c,miR-30b and miR-30e+,etc.The significantly down-expressed microRNA was miR-338-5p.The bioinformatics analysis results indicated that TRAF3 was the targeted gene of miR-338-5p,which was testified by real time PCR,immunohistochemical assay and fluorescence reporter assay.Conclusion miR-338-5p anticipated in the antibody-mediated renal allograft rejection by targeting TRAF3.

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Experimental study on subzero nonfreezing preservation of rat kidney

Long YANG ; Hewei MEN ; Yabo WANG ; Kai ZHU ; Yamin ZHANG

Chinese Journal of Organ Transplantation.2013;34(9):559-562. doi:10.3760/cma.j.issn.0254-1785.2013.09.012

Objective To search for the most appropriate subzero nonfreezing temperature,and explore the effect of subzero nonfreezing preservation of rat kidney by comparing with the kidney preservation with conventional temperature (4 ℃,0 ℃) and freezing temperature (-4 ℃).Method The thermocouple probeand the temperature data logging device were used to detect the temperature decreasing curves in different parts of the rat kidney and determine the freezing point of the kidney.The perfused kidneys in rats were removed and put into the sterile tubes containing 2.5 mL hypertonic citrate adenine.Following 6 group were set up:-0.8 ℃ group (subzero nonfreezing),-0.5 ℃group (subzero nonfreezing),0 ℃ group (zero nonfreezing),-4 ℃ group (control group),-1 ℃group(subzero freezing)、-4 ℃ group (subzero freezing).After the cryopreservation for 24 and 48 h,the preservative fluid was harvested for measurement of the contents of LDH and AST,and the paraffin sections from the upper pole of the kidney were made for observation of the pathological changes and apoptosis.Result The freezing temperature of kidney was-1℃ and the most appropriate subzero nonfreezing temperature for preserving the rat kidney was-0.8 ℃.Subzero nonfreezing significantly inhibited the basal metabolic rate of the histiocytes,reduced the contents of LDH and AST released due to the membrane damage,and decreased the apoptosis rate [48 h:-0.8 ℃ (40.1 ± 7.0) ％ vs.4 ℃ (47.1 ± 7.6) ％].Under the light microscope after preservation for 48 h,the pathological changes in-0.8 ℃ group were less than in 4 ℃ group.Conclusion Compared with the organ preservation in conventional temperature (0 ℃-4 ℃),the subzero nonfreezing (-0.8 ℃) can further inhibit the basal metabolic rate of histocytes obviously,reduce its energy consumption,and lower the apoptosis caused by low temperature damage.

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Application of liver grafts from HBsAg positive donors in liver transplantation for hepatocellular carcinoma beyond UCSF Criteria

Xinguo CHEN ; Zhongyang SHEN ; Yujian NIU ; Shan SHAN ; Letian WANG ; Li LI ; Jun LI

Chinese Journal of Organ Transplantation.2013;34(9):528-531. doi:10.3760/cma.j.issn.0254-1785.2013.09.005

Objective To evaluate the outcomes of liver transplant recipients who received liver grafts from HBsAg positive donors in patients with hepatocellular carcinoma beyond UCSF (University of California,San Francisco) Criteria.Method The medical records of patients who underwent HBsAg-positive donor liver transplantation for hepatocellular carcinoma beyond UCSF Criteria from October 2008 to December 2012 at our hospital were analyzed retrospectively,including the existence status of HBV,graft function,tumor recurrence,and the survival after transplantation.Result A total of 20 patients were enrolled in the study.One patient lost follow-up while the remaining 19 patients had complete follow-up data.All the patients were followed up until June 2013,with a median follow-up duration of 12 months (range 2-57 months).One patient died from postoperative abdominal bleeding and multiple organ failure at post-transplantative day 21.Five patients survived up to now,including 4 cases with disease-free survival,who has been surviving for 57,35,26 and 12 months respectively.The remaining all 14 patients died from tumor recurrence at different time points after transplantation.Entecavir was used alone in 19 patients and Entecavir combined with Adefovir dipivoxilalone were used as anti-HBV therapy in the recipients.At posttransplant day 45,all the recipients were positive for serum HBsAg and negative for serum HBVDNA,and the liver enzymatic criteria,coagulation criteria and the serum bilirubin restored to normal levels or within twice the upper limit of normal levels.Throughout the follow-up period,recipients were all positive for serum HBsAg,but there was no recurrence of hepatitis B.The 1-,2-,3-and 4-year cumulative survival rate was 48.0％,35.0％,18.7％ and 18.7％ respectively.Conclusion The HBsAg positive liver may be used as a donor in liver transplantation and the graft probably works well after the operation.Liver transplantation may prolong the survival and improve the quality of life,even achieve long-term disease-free survival in patients with hepatocellular carcinoma beyond UCSF Criteria.The use of nucleotide analogue only,instead of combination with hepatitis B immune globulin,can also bring HBV well under control in liver transplant recipients with HBsAg positive donors.

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Anxiety and depression of liver transplant recipients and the related impact factors

Yuan LIAO ; Zongheng ZHENG ; Ming HAN ; Xiongying PAN ; Meijuan WU ; Shouzhen CHENG

Chinese Journal of Organ Transplantation.2013;34(9):537-541. doi:10.3760/cma.j.issn.0254-1785.2013.09.007

Objective To evaluate the anxiety and depression status of the liver transplant recipients and to investigate the related impact factors.Method Forty-two liver transplant recipients were under survey by General Information Questionnaire (GIQ),Social Support Rating Scale (SSRS),Self-rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) before and 1,6,12,24 and 36 months after operation.Result The mean anxiety scores before and 1,6,12,24 and 36 months after operation were 37.2 ± 5.3,32.2 ± 6.2,32.1 ± 6.6,31.9± 5.1,30.1 ± 4.6 and 28.5 ± 4.1,respectively.The mean depression scores at those 6 time points were 46.7 ± 7.1,37.9 ± 10.7,36.7 ±7.9,37.1 ± 6.4,34.3 ± 5.8 and 32.1 ± 5.6,respectively.Both the anxiety and depression scores showed statistically significant difference (P＜0).001) before and after operation (all time points).Also there was statistically significant difference (P＜0.001) between post-operative month 36 and other post-operative time points.The impact factors for anxiety of liver transplant recipients were subjective supports and the utilization level of the supports.The impact factors of depression of liver transplant recipients were pre-operative depression score,objective support,subjective supports and the utilization level of the supports.Conclusion Liver transplant recipients suffer less anxiety and depression after operation.The anxiety status can be further improved from 24 to 36 months postoperation.

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The frequency of Toll-like receptor 4 polymorphisms Asp299Gly and Thr399Ile in 208 hematopoietic stem cell transplant recipients and their donors

Yi ZHAO ; Lijuan WANG ; Yi LUO ; Jimin SHI ; Yamin TAN ; He HUANG ; Zhen CAI

Chinese Journal of Organ Transplantation.2014;35(1):13-16. doi:10.3760/cma.j.issn.0254-1785.2014.01.004

Objective To determine the frequency of Toll-like receptor 4 (TLR4)polymorphisms Asp299Gly and Thr399Ile in a cohort of hematopoietic stem cell transplant recipients and their donors in China.Method We examined the polymorphisms in 208 peripheral blood samples collected from 104 recipients and their donors in a single center between 2007-2012 in Zhejiang Province,China,and Asp299Gly and Thr399Ile TLR4 gene polymorphisms were detected using the sample DNA amplification products direct sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.Result Both methods didn't demonstrate TLR4 polymorphisms Asp299Gly or Thr399Ile base mutation in our samples.Conclusion The TLR4 Asp299Gly and Thr399Ile polymorphisms are very rare in our part of the population of hematopoietic stem cell transplantation.

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The analysis of risk factors in gastrointestinal graft versus host disease following allogeneic hematopoietic stem cell transplantation

Jun GUAN ; Youshan ZHANG ; Jinhuan XU ; Jin YIN ; Yang CAO ; Yicheng ZHANG

Chinese Journal of Organ Transplantation.2014;35(1):17-20. doi:10.3760/cma.j.issn.0254-1785.2014.01.005

Objective To investigate the risk factors of gastrointestinal graft versus host disease(GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).Method 214 patients receiving allo-HSCT from 2003 to 2012 were enrolled in this study,and assessed on the degree of gastrointestinal GVHD.The effects of the primary diseases status,gender,age,conditioning regimen intensity,donor type,the number of cells positive for the CD34 expression,and the use of anti-lymphocyte immunoglobulin (ALG) in the pretreatment scheme on the occurrence of gastrointestinal GVHD was studied.The responses of different degrees of GVHD to immunotherapy were evaluated.Result Univariate and multivariate analyses revealed that the graft type and the conditioning regimen intensity were the risk factors of gastrointestinal GVHD (P＜0.05).Conclusion Donor type and conditioningregimen intensity may be the main risk factors of gastrointestinal GVHD.

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Preoperative treatment and prognosis observation in sensitized recipients of kidney transplantation

Xianlin WANG ; Lixin YU ; Min LUO ; Yun MIAO ; Lulu XIAO

Chinese Journal of Organ Transplantation.2014;35(2):73-76. doi:10.3760/cma.j.issn.0254-1785.2014.02.003

Objective To study the preoperative treatment and prognosis observation? in sensitized recipients of kidney transplantation.Method Forty-one recipients positive for preoperative PRA accepted renal allograft transplantation from January 2007 to July 2012.All recipients were given immunosuppressant or immune induction by anti-CD25rnAb in advance,and plasma exchange,immunoadsorption and intravenous high-dose immune globulin were administered.Meanwhile,donor HLA antigens had to avoid all stored HLA antibodies of the recipient,and lymphocyte cytotoxicity cross test (CDC) had to be negative.Anti-human lymphocyte globulin (ATG) was used to strengthen the immune induction,and tacrolimus + mycophenolate mofetil (MMF) + corticosteroids triple immunosuppressive regimen was adopted after transplantation.Then intravenous micafungin would be given after transplanted kidney function was normal,and ganciclovir and sulfamethoxazole were taken orally to prevent infection.Result In 41 recipients positive for preoperative PRA,13 cases were positive for only HLA class Ⅰ antibodies,15 cases for only HLA class Ⅱ antibodies,and there existed 13 cases of both HLA class Ⅰ and class Ⅱ antibodies also with PRA≥50％.Fifteen patients achieved normal serum creatinine in one week,and no hyperacute rejection and accelerated rejection occurred.Fourteen recipients experienced an episode of acute rejection (34.15％,14/41): 12 recovered by steroids bolus therapy,and the other two reversed in 3-5 days by cyclophosphamide or ATG treatment.One case died of mycotic pneumonia in 4 months later.One-year recipient/kidney survival rate was 97.6％ (40/41).Conclusion The recipients positive for preoperative PRA only can accept renal allograft transplant while the donor's HLA antigens had to avoid all stored HLA antibodies of recipients themselves and CDC test was negative.After that the combination of desensitization therapy,immune induction therapy and postoperative potent immunosuppressant can prevent acute rejection effectively and increase postoperative recipient/kidney survival rate.

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