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ABSTRACT: Recent studies have indicated the value of increased blood eosinophil counts for the diagnosis of acute cellular rejection (ACR) after orthotopic liver transplantation (OLT). However, the relationship between eosinophil count and late ACR at more than 6 months after OLT is still unclear.
We sought to retrospectively analyzed the ACR predictive value of eosinophil counts. In the day before or the day of biopsy among 40 biopsies performed on 37 patients beyond 6 months after OLT.
Relative eosinophil count was significantly higher in the ACR (n = 24) than the non-ACR cohort, albeit with no significant difference in absolute eosinophil count. Receiver operating characteristic (ROC) analysis showed an absolute eosinophil count of 0.145 × 10(9)/L and a relative eosinophil count of 2.3% to show the highest Youden index with area under the ROC curves of 0.746 and 0.813, respectively. When absolute eosinophil count ≥0.145 × 10(9)/L or relative eosinophil count ≥2.3% was defined to be elevated, the sensitivity and specificity to predict ACR were 45.8% and 87.5%, and 75% and 87.5%, respectively. When the absolute eosinophil count ≥ 0.285 × 10(9)/L or relative eosinophil count ≥3% was defined as elevated, the sensitivity and specificity were 25% and 100%, and 50% and 100%, respectively. All patients with an absolute eosinophil count ≥0.285 × 10(9)/L showed a relative eosinophil count ≥3%.
Elevated blood eosinophil count was a valuable biomarker to predict late ACR after OLT.
Transplantation Proceedings 04/2013; 45(3):1198-200. · 1.00 Impact Factor
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ABSTRACT: Intrahepatic cholangiocarcinoma (ICC) is not a widely accepted indication for liver transplantation (LT). The present study describes our institutional experience with patients who underwent transplantation for ICC.
A retrospective analysis was performed on 11 consecutive patients with ICC who underwent LT between October 2003 and November 2008 at our institution.
At a median patient follow-up interval of 10 months (2-56), the median survival time was 9 months (2.5-53). The perioperative mortality and the recurrence rate were 0 and 45.5%, respectively. Five patients are currently alive 10, 12, 41, 51 and 53 months after LT, respectively. One patient died 3 months after LT as a result of bile leak and toxic shock, and 5 patients died of tumor recurrences at 2.5, 8, 8, 9 and 10 months post-LT, respectively. The 1-, 2-, 3- and 4-year disease-free survival rates and overall survival rates of all the patients were 51.9, 51.9, 51.9 and 51.9%, and 50.5, 50.5, 50.5 and 50.5%, respectively.
With better and strict patient selection, the prognosis of LT for ICC could be improved. ICC patients with lymph node involvement, vascular or bile duct invasion are contraindicated for LT.
European Surgical Research 01/2011; 47(4):218-21. · 0.93 Impact Factor
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ABSTRACT: Rapamycin (Rapa), a recently introduced immunosuppressive drug, appears to be effective in preventing acute allograft rejection episodes. Its effects on differentiation and maturation of dendritic cells (DCs) have been studied. In this report, we evaluated the effects of Rapa on the intracellular signal transduction pathways in mature DCs. The results showed that Rapa did not depress p65, p50, or IkappaBalpha expression. However, it dramatically reduced activator protein-1 activation. The fact that Rapa exerts a specific effect on activator protein-1 activity in mature DCs may contribute to its unique actions to prevent allograft rejection and induce immune tolerance.
Transplantation Proceedings 06/2010; 42(5):1881-3. · 1.00 Impact Factor
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ABSTRACT: Blockade of a costimulatory pathway by adenovirus-mediated cytotoxic T lymphocyte associated antigen 4 immunoglobulin (CTLA4-Ig) gene transfer and anti-CD40L mAb(MR1) have been reported to enhance graft survival in several experimental transplantation models. In this study, we investigated the effects of gene transfer of CTLA4Ig and MR1 on islet xenograft rejection in mice. Recombinant adenovirus AdCTLA4Ig was constructed to express CTLA4Ig. Islet grafts from adult male DA rats transferred with AdCTLA4Ig were transplanted to streptozocin-induced diabetic Balb/c mice. The diabetic mice were treated with MR1 after transplantation. We evaluated the islet xenograft mean survival time as well as changes in interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) levels in transplanted mice. The mean survival of islet xenografts in the MR1 treatment group was 34.9 +/- 5.62 days, in the AdCTLA4Ig treatment group it was 56.5 +/- 10.64 days, and in the AdCTLA4Ig plus MR1 treatment group it was 112.9 +/- 19.26 days, all significantly prolonged compared with an untreated group (8.1 +/- 0.83 days). Within 1 week after transplantation the levels of IL-2 and TNF-alpha showed sharp increases in the untreated group, being significantly higher than those observed prior to transplantation. In conclusion, using both AdCTLA4Ig and MR1 can improve the islet xenograft survival. The beneficial effects of the combined use of the 2 reagents were superior to either 1 alone, possibly related to down-regulated expression of Th1 cell-related cytokines.
Transplantation Proceedings 06/2010; 42(5):1835-7. · 1.00 Impact Factor
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G-H Chen,
G-Y Wang,
Y Yang, H Li,
M-Q Lu,
C-J Cai,
G-S Wang,
C Xu,
S-H Yi,
J-F Zhang,
B-S Fu
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ABSTRACT: Hepatic artery stenosis (HAS) is a potentially life-threatening complication of liver transplantation because the associated mortality and morbidity rates are high. Surgical reconstruction was recommended as first choice of treatment and interventional radiologic techniques have been introduced recently. However, the mid- or long-term outcomes of HAS were unclear. The purpose of this study was to evaluate the efficacy of interventional therapy and clinical outcomes of HAS following liver transplantation.
A retrospective analysis was performed for 20 cases of HAS documented by angiography from October 2003 to August 2007 at the authors' institution. All patients underwent transluminal interventional therapy including percutaneous transluminal angioplasty and endovascular stent placement. The technical results, hepatic artery patency and clinical outcome were reviewed.
All patients were treated with interventional management. Technical and immediate success was 100%. Of 8 patients with early HAS (within 1 month of transplantation), 1 underwent retransplantation due to deterioration of liver function. One died of acute liver failure waiting for retransplantation. Of 12 patients with late HAS (after 1 month of liver transplantation), 1 died of severe sepsis 38 days after transplantation. Five patients underwent late retransplantation due to ischemic-type biliary strictures or recurrent attacks of cholangitis. One of these patients died 11 days after retransplantation. The median follow-up of all 20 patients was 14.4 months after liver transplantation. The Kaplan-Meier curve of patency showed that cumulated primary patency of hepatic artery interventional treatment at 3, 6 and 12 months was 94, 87 and 79%, respectively. Two patients died of causes unrelated to HAS. Three patients developed recurrent HAS and were successfully treated with second interventional therapy. Eight patients (40%) developed ischemic-type biliary strictures and 7 underwent endoscopic treatment or percutaneous transhepatic cholangiodrainage. Graft function in 5 patients improved. The Kaplan-Meier curve of survival showed that the 1- and 2-year cumulated survival rates of early and late HAS were 87.5 and 43.8% and 81.5 and 61.1%, respectively. There was no significant difference in 1- and 2-year survival rates between early and late HAS (log-rank test, p = 0.928).
Interventional therapy is an effective treatment for both early and late HAS with excellent short- and mid-term outcomes, while without irreversible graft dysfunction resulted from HAS. However, the patients have a high incidence of ischemic-type biliary lesions.
European Surgical Research 11/2008; 42(1):21-7. · 0.93 Impact Factor
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ABSTRACT: With the accumulation of orthotopic liver transplantation (OLT) recipients, an increased number of patients with graft failure need retransplantation (re-OLT). This study was undertaken to examine our clinical experience of re-OLT for patients with poor graft function after primary transplantation at a single center. We analyzed retrospectively, the clinical data of 32 re-OLTs in 31 patients at our center from January 2004 to February 2007, including indications and causes of death, timing of retransplantation, and surgical techniques. The indications included bile leak (2 cases), biliary stricture (16 cases), recurrence of hepatocellular carcinoma (HCC) (5 cases), hepatic artery stenosis (4 cases), hepatic artery thrombosis (HAT) (2 cases), and hepatitis B recurrence (3 cases). The rate of re-OLT was 4.29%. All patients underwent modified piggyback liver transplantations with cadaveric allografts. No intraoperative mortality and acute rejection occurred. Overall, 17 of 31 patients (54.8%) died after re-OLT with survival times ranging from 2 weeks to 28 months. Another 14 patients were cured with survival times of 4 to 32 months. The perioperative mortality rate of patients who underwent re-OLT between 8 and 30 days after their initial transplantation was highest (66.7%). The most common cause of death after re-OLT was sepsis (47.1%), multiple-organ failure (17.6%), and recurrence of HCC (17.6%), whereas the majority of deaths posttransplantation were sepsis-related (54%) within 1 year. Re-OLT is the only therapeutic option for a failing liver graft. Proper indications and optimal operative time, advanced surgical procedures, reasonable individual immunosuppression regimens, and effective perioperative anti-infection treatments contribute to the improved survival of patients after re-OLT.
Transplantation Proceedings 07/2008; 40(5):1485-7. · 1.00 Impact Factor
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ABSTRACT: Cellular apoptosis plays an important role in ischemia-reperfusion (I/R) injury during organ transplantation. Synthetic small interference RNA (siRNA) targeting apoptotic receptor Fas has proven effective to protect mice against hepatitis and renal I/R injury. The objective of this study is to investigate the silencing impact of Fas siRNA to alleviate I/R injury in rat liver transplantation.
Rat hepatocytes (BRL cells) were transfected with three pairs of synthesized Fas siRNA; cells untreated and treated with GFP siRNA were taken as blank and siRNA control. The most effective Fas siRNA was chosen for in vivo experiments. Syngeneic orthotopic liver transplantation was performed in Fas siRNA group, siRNA control group, and blank control group of Sprague-Dawley rats. There were 25 pairs of rats in each group. siRNA transfection of donor rats was done with hydrodynamic injection method 48 h before liver procurement. Blood and liver samples were collected for evaluation of serum ALT levels, Fas protein and mRNA expression, and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, 1, 3, 6, 12, and 24 h after liver transplantation.
Fas siRNA2, which inhibited Fas gene expression much more than other siRNAs, was chosen for in vivo experiment. The serum ALT levels of Fas siRNA group were much less than those of blank and siRNA control groups 1, 3, 6, 12, and 24 h after blood reperfusion, indicating diminishing ischemia-reperfusion injury. Donor livers in Fas siRNA group had substantially less cell apoptosis. The expression of Fas mRNA and protein was reduced dramatically in the Fas siRNA group compared with the other two groups.
Fas-mediated apoptosis play an important role in I/R injury of rat liver transplantation. Silencing Fas by hydrodynamic injection of siRNA holds therapeutic promise to limit I/R injury.
Langenbeck s Archives of Surgery 06/2007; 392(3):345-51. · 1.81 Impact Factor
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ABSTRACT: Ponicidin is recently reported to have anti-tumour effects on a large variety of cancers. The present study was undertaken to investigate the anti-proliferation effects of ponicidin on hepatocellular carcinoma cells and its mechanism.
Two hepatocellular carcinoma cell lines, QGY-7701 and HepG-2 cells, were used. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis was assessed by flow cytometry and deoxyribonucleic acid fragmentation analysis. Cell morphology was observed by Hoechst 33258 staining. Reverse transcriptase-polymerase chain reaction and Western blot analysis were used to detect Survivin as well as Bax and Bcl-2 expressions.
Ponicidin could inhibit the growth of QGY-7701 and HepG-2 cells significantly by induction of apoptosis. Marked morphological changes of apoptosis were observed clearly. Both Survivin and Bcl-2 expressions were down-regulated remarkably while Bax expression up-regulated when apoptosis occurred.
Ponicidin has significant anti-proliferation effects by inducing apoptosis on hepatocellular carcinoma cells in vitro, down regulation of Survivin and Bcl-2 as well as upregualation of Bax expressions may be the important apoptotic inducing mechanisms.
Digestive and Liver Disease 03/2007; 39(2):160-6. · 3.05 Impact Factor
