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1.
Ann Palliat Med ; 10(8): 8584-8595, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34379984

ABSTRACT

BACKGROUND: The efficacy of early allograft dysfunction (EAD) definitions in predicting post-transplant graft survival in a Chinese population is still unclear. METHODS: A total of 607 orthotopic liver transplants (OLT) have been included in the current study. Model accuracy was evaluated using receiver operating characteristic (ROC) analysis. Risk factors for EAD was evaluated using univariable analysis and multivariable logistic regression model. RESULTS: The 3-, 6-, and 12-month patient/graft survival were 91.6%/91.4%, 91.1%/90%, and 87.5%/87.3%, respectively. MELDPOD5 had a superior discrimination of 3-month graft survival (C statistic, 0.83), compared with MEAF (C statistic, 0.77) and Olthoff criteria (C statistic, 0.72). Multivariate analysis of risk factors for EAD defined by MELDPOD5, showed that donor body mass index (P=0.001), donor risk index (P=0.006), intraoperative use of packed red blood cells (P=0.001), hypertension of recipient (P=0.004), and preoperative total bilirubin (P<0.001) were independent risk factors. CONCLUSIONS: The results suggest that MLEDPOD5 is a better criterion of EAD for the Chinese population, which might serve as a surrogate end-point for graft survival in clinical study.


Subject(s)
Liver Transplantation , Primary Graft Dysfunction , Allografts , Graft Survival , Humans , Retrospective Studies , Risk Factors , Time Factors
3.
Liver Transpl ; 23(9): 1161-1170, 2017 09.
Article in English | MEDLINE | ID: mdl-28422396

ABSTRACT

In liver transplant patients with type 2 diabetes mellitus (DM), the disease worsens after transplantation because of longterm use of diabetogenic immunosuppressive drugs, making management of those patients a great challenge. The objective of our study was to evaluate the safety and efficacy of a simplified multivisceral transplantation (SMT) procedure for the treatment of patients with end-stage liver disease and concurrent type 2 DM. Forty-four patients who had pretransplant type 2 DM were included. A total of 23 patients received SMT, and 21 patients received orthotopic liver transplantation (OLT). Patient and graft survivals, complications, diabetic control, and quality of life (QOL) were retrospectively analyzed in both groups. The 1-, 3-, and 5-year cumulative patient and graft survival rates were 91.5%, 75.4%, and 75.4% in the SMT group and were 94.4%, 64.4%, and 64.4% in the OLT group, respectively (P = 0.70). Interestingly, 95.7% (22/23) of patients achieved complete remission from DM after SMT compared with 16.7% (3/18) of patients after OLT. The occurrence of biliary complication was significantly higher in the OLT group than that in the SMT group (23.8% versus 0.0%; P = 0.01). Moreover, better QOL was observed in the SMT group than that in the OLT group. In conclusion, the SMT procedure we described here is a safe and viable option for patients with end-stage live disease and concurrent type 2 DM. This SMT procedure offers excellent transplant outcomes and QOL. Liver Transplantation 23 1161-1170 2017 AASLD.


Subject(s)
Diabetes Mellitus, Type 2/surgery , End Stage Liver Disease/surgery , Immunosuppressive Agents/adverse effects , Liver Transplantation/methods , Postoperative Complications/epidemiology , Adult , Aged , Biliary Tract Diseases/epidemiology , Biliary Tract Diseases/etiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/mortality , End Stage Liver Disease/complications , End Stage Liver Disease/mortality , Feasibility Studies , Female , Follow-Up Studies , Graft Rejection/prevention & control , Graft Survival , Humans , Liver Transplantation/adverse effects , Male , Middle Aged , Postoperative Complications/etiology , Quality of Life , Retrospective Studies , Surveys and Questionnaires , Survival Rate , Treatment Outcome
4.
Hepatobiliary Pancreat Dis Int ; 13(4): 409-15, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25100126

ABSTRACT

BACKGROUND: In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot program. METHODS: From July 2011 to August 2012, our center performed 26 liver transplants from a pool of 29 deceased donors. All organ donation and allograft procurement were conducted according to the national protocol. The clinical data of donors and recipients were collected and summarized retrospectively. RESULTS: Among the 29 donors, 24 were China Category II donors (organ donation after cardiac death), and five were China Category III donors (organ donation after brain death followed by cardiac death). The recipients were mainly the patients with hepatocellular carcinoma. The one-year patient survival rate was 80.8% with a median follow-up of 422 (2-696) days. Among the five mortalities during the follow-up, three died of tumor recurrence. In terms of post-transplant complications, 9 recipients (34.6%) experienced early allograft dysfunction, 1 (3.8%) had non-anastomotic biliary stricture, and 1 (3.8%) was complicated with hepatic arterial thrombosis. None of these complications resulted in patient death. Notably, primary non-function was not observed in any of the grafts. CONCLUSION: With careful donor selection, liver transplant from deceased donors can be performed safely and plays a critical role in overcoming the extreme organ shortage in China.


Subject(s)
Brain Death , Carcinoma, Hepatocellular/surgery , Donor Selection , Heart Diseases/mortality , Liver Neoplasms/surgery , Liver Transplantation/methods , Tissue Donors/supply & distribution , Adult , Aged , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , China , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Male , Middle Aged , Neoplasm Recurrence, Local , Pilot Projects , Program Evaluation , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome
5.
Tumour Biol ; 35(2): 1057-63, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24061638

ABSTRACT

The purposes of the present work were to construct the shRNA plasmids for BAG-1 gene of human and test the expression of mRNA and protein of BAG-1. Recombinant plasmids containing green fluorescent protein reporter genes are constructed using gene cloning methods. The shRNA plasmids for the BAG-1 gene are constructed by RNA interference technology. We applied fluorescent plasmid-transfected target cells in the cell transfection experiments and monitored the transfection rate of plasmids by observing the fluorescence amount. We transfected three synthesized shRNA in target screening cell and adopted RT-PCR and Western test to identify the difference of target gene transfection and translation level in cells. The specific shRNA plasmid for the BAG-1 gene was successfully recombined, and stably transfected colon cancer Lo Vo cell lines were obtained. The results present that the constructed shRNA plasmids significantly inhibited the expression of mRNA and protein of Lo Vo cell BAG-1, and can maintain the effect for a long term. pGPH1/GFP/Neo-BAG-1-homo-825 was screened as the optimum sequence of interference so as to lay a solid foundation to explore into the research on the BAG-1 gene and the biological behavior of colon cancer cells. It showed the remarkable advantage of RNAi in the generation of posttranscriptional gene silencing.


Subject(s)
Colonic Neoplasms/genetics , DNA-Binding Proteins/genetics , Gene Expression Regulation, Neoplastic/genetics , RNA Interference , Transcription Factors/genetics , Cell Line, Tumor , Cell Proliferation , Colonic Neoplasms/pathology , DNA-Binding Proteins/antagonists & inhibitors , Genetic Vectors , Green Fluorescent Proteins/genetics , Humans , Plasmids/genetics , Transcription Factors/antagonists & inhibitors , Transfection
6.
J Surg Res ; 187(2): 471-83, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24290429

ABSTRACT

BACKGROUND: Conflicting results were found between radiofrequency-assisted liver resection (RF-LR) and clamp-crush liver resection (CC-LR) during liver surgery. We conducted a systematic review and meta-analysis that included randomized controlled trials (RCTs) and non-RCTs to compare the effectiveness and safety of RF-LR versus CC-LR during liver surgery. METHODS: Articles comparing RF-LR and CC-LR that were published before December 2012 were retrieved and subjected to a systematic review and meta-analysis. Data synthesis and statistical analysis were carried out by Review Manager Version 5.2 software. RESULTS: In all, four RCTs and five nonrandomized studies evaluating 728 patients were included. Compared with CC-LR, the RF-LR group had significantly reduced total intraoperative blood loss (weighted mean difference [WMD] = -187 mL; 95% confidence interval [CI] = -312, -62; data on 628 patients), and blood loss during liver transection (WMD = -143.7 mL; 95% CI = -200, -87; data on 190 patients). However, RF-LR is associated with a higher rate of intra-abdominal abscess than the clamp-crushing method (odds ratio = 3.61; 95% CI = 1.26, 10.32; data on 366 patients). No significant difference was observed between both the groups for the incidence of both blood transfusion and bile leak. CONCLUSIONS: There is currently not sufficient evidence to support or refute the use of RF-LR in liver surgery. RF-LR has advantages in terms of reducing blood loss. However, RF-LR may increase the rates of both bile leak and abdominal abscess. So, the safety of RF-LR has not been established. Future well-designed RCTs are awaited to further investigate the efficacy and safety of RF devices in liver resection.


Subject(s)
Catheter Ablation/methods , Hemostasis, Surgical/methods , Hepatectomy/methods , Liver Diseases/surgery , Liver Neoplasms/surgery , Hepatectomy/instrumentation , Humans , Randomized Controlled Trials as Topic , Surgical Instruments
7.
J Dig Dis ; 14(8): 433-8, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23615075

ABSTRACT

OBJECTIVE: To evaluate the role of positron emission tomography/computer tomography with fluorine-18 fluorodeoxyglucose ((18) F-FDG-PET/CT) in detecting hepatocellular carcinoma (HCC) recurrence after hepatectomy and/or radiofrequency ablation (RFA) and to compare its efficacy with contrast-enhanced ultrasound (CEUS). METHODS: A total of 36 HCC patients were included in this study. All patients underwent both (18) F-FDG-PET/CT and CEUS at least once for the diagnosis of HCC recurrence. The time interval between PET/CT and CEUS was 14 ± 3 days. All patients were followed up for at least 24 months. RESULTS: In all, 32 patients were confirmed to have HCC recurrence by pathology and clinical follow-up. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of (18) F-FDG-PET/CT for intrahepatic HCC recurrence were 96.7%, 83.3%, 96.7%, 83.3% and 94.4%, respectively. The corresponding values of CEUS were 56.7%, 100%, 100%, 31.6% and 63.9%, respectively. The sensitivity and accuracy of (18) F-FDG-PET/CT for the diagnosis of HCC recurrence were significantly higher than those of CEUS (P < 0.01, respectively). CONCLUSIONS: Compared with CEUS, (18) F-FDG-PET/CT has higher sensitivity and accuracy in detecting the local recurrence of HCC after hepatectomy and/or RFA. It can be used to detect recurrent extrahepatic lesions of HCC effectively.


Subject(s)
Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , Neoplasm Recurrence, Local/diagnosis , Adult , Aged , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/secondary , Carcinoma, Hepatocellular/surgery , Catheter Ablation , Female , Fluorodeoxyglucose F18 , Hepatectomy , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Male , Middle Aged , Multimodal Imaging/methods , Neoplasm Recurrence, Local/diagnostic imaging , Positron-Emission Tomography/methods , Predictive Value of Tests , Radiopharmaceuticals , Sensitivity and Specificity , Tomography, X-Ray Computed/methods , Ultrasonography
8.
J Dig Dis ; 14(1): 38-44, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23134408

ABSTRACT

OBJECTIVE: To evaluate the safety and efficacy of steroid-minimization therapy in liver transplantation (LT) recipients with hepatitis B virus-related diseases in China. METHODS: From March 2000 to June 2007, 502 adult LT recipients, mostly with hepatitis B (HBV)-related diseases, were enrolled in our study. Four study groups were setup according to the steroid-minimization protocols: tacrolimus (TAC) with 6 months steroids withdrawal (6M SW), TAC with 3 months SW (3M SW), TAC with 14 days SW (14d SW), and TAC with basiliximab induction and steroids avoidance (Bas SA). All patients were followed up for at least 36 months after LT. RESULTS: There were no significant differences in the overall 3-year survival rates of the patients and graft, and chronic rejection among the four groups (P = 0.092, P = 0.113 and P = 0.684, respectively). There was also no difference in acute rejection within 12 months after LT (P = 0.514). The 3-year recurrence rates of HBV infection and hepatocellular carcinoma (HCC) after LT were significantly different among all the groups (lowest in TAC/Bas SA group; P = 0.037 and P = 0.029, respectively). The overall incidence of infection was significantly higher in the 6M SW group (62.2% vs 56.1% in 3M SW, 30.5% in 14d SW, 20.5% in Bas SA; P < 0.01). By the end of the 3-year follow-up, more than 90% of the surviving patients could safely receive TAC monotherapy. CONCLUSION: Bas SA immunosuppressive protocol can be achieved safely in LT and reduce HBV infection and HCC recurrence and side effects of steroids after LT.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Carcinoma, Hepatocellular/surgery , Immunosuppressive Agents/administration & dosage , Liver Neoplasms/surgery , Liver Transplantation/methods , Methylprednisolone/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Tacrolimus/administration & dosage , Adult , Antibodies, Monoclonal/adverse effects , Bacterial Infections/etiology , Basiliximab , Chi-Square Distribution , Female , Follow-Up Studies , Graft Rejection/immunology , Graft Rejection/prevention & control , Graft Survival , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/drug therapy , Humans , Immunosuppressive Agents/adverse effects , Liver Cirrhosis/surgery , Liver Cirrhosis/virology , Liver Transplantation/immunology , Male , Methylprednisolone/adverse effects , Middle Aged , Neoplasm Recurrence, Local/immunology , Recombinant Fusion Proteins/adverse effects , Recurrence , Statistics, Nonparametric , Survival Rate , Tacrolimus/adverse effects
9.
Cancer Biother Radiopharm ; 27(8): 490-4, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22988970

ABSTRACT

AIMS: The purpose of the present work was to formulate and evaluate cationic nano-liposomes as novel nonviral gene delivery for colon cancer treatment. METHODS: Recombinant pEGFP-c1-Fms-like tyrosine kinase receptor 3 ligand (FL) plasmids containing human FL gene and green fluorescent protein (GFP) reporter genes were constructed. FL and GFP Gene-carrying cationic nano-liposomes were prepared based on the electrostatic adherence principle and then transfected into Lovo cells. The morphology, particle size, and zeta potential of gene-carrying cationic nano-liposomes were observed using an electron microscope. GFP expression was observed by fluorescence microscopy to assay the transfection efficiency. The cytotoxicity of FL/nano-liposomes was evaluated by the MTT method. RESULTS: Recombinant plasmids pEGFP-c1-FL are successfully constructed using gene cloning methods and confirmed by restriction enzyme digestion and sequencing. The cationic nano-liposomes carrying pEGFP-cl-FL were observed by an electron micrograph and showed uniform spherical or elliptical shapes and many pores. The fluorescence microscopy images of gene-carrying cationic nano-liposomes showed good expression of GFP in pEGFP and pEGFP-cl-FL groups. The MTT assay of cell death indicated a significantly higher level of cell death between the FL group and the control group at 24, 48, and 96 hours after transplantation. CONCLUSION: Cationic nano-liposomes show safe and high-performance transfection as gene carriers. Gene therapy has significant implications for colon cancer treatment in future.


Subject(s)
Colonic Neoplasms/therapy , Gene Transfer Techniques , Green Fluorescent Proteins/genetics , Membrane Proteins/genetics , Nanoparticles/chemistry , Recombinant Fusion Proteins/genetics , Transfection/methods , Base Sequence , Cell Line, Tumor , Colonic Neoplasms/genetics , Gene Expression , Green Fluorescent Proteins/chemistry , Humans , Liposomes/administration & dosage , Liposomes/chemistry , Male , Membrane Proteins/chemistry , Microscopy, Fluorescence , Middle Aged , Molecular Sequence Data , Nanoparticles/administration & dosage , Plasmids/administration & dosage , Plasmids/genetics , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/chemistry
10.
Zhonghua Yi Xue Za Zhi ; 92(18): 1264-7, 2012 May 15.
Article in Chinese | MEDLINE | ID: mdl-22883065

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of sorafenib in the prevention and treatment of hepatocellular carcinoma (HCC) relapse after liver transplantation. METHODS: A retrospective cohort study was performed to assess the efficacy and safety of sorafenib for HCC. Forty-four patients who underwent liver transplant for HCC beyond Milan criteria form July 2007 to May 2010 were included study group (sorafenib, n = 22) and control group (without sorafenib, n = 22). The primary endpoints of the study were disease-free survival (DFS), overall survival (OS). Secondary outcomes included the rates of acute rejection and graft survival. RESULTS: The clinical data of 44 patients were completely collected. There were significantly differences between sorafenib group and control group in 1-year DFS (81.8% (n = 18) vs 63.6% (n = 14), P < 0.05) and OS (90.9% (n = 20) vs 72.7% (n = 16), P < 0.05) respectively. The acute rejection rates in Sorafenib were 13.6% (3/22), compared with 18.2% (4/22) in control group (P = 0.524) and 1-year graft survival in Sorafenib group were 86.4% (19/22), compared with 72.7% (16/22) in control group (P = 0.086). The overall incidence of treatment-related adverse events was 68.1% (n = 15) in sorafenib group and 31.8% (n = 7) in the control group (P < 0.01). Adverse events that were reported for patients receiving sorafenib were predominantly grade 1 or 2 in severity including diarrhea (45.5%, n = 10), liver dysfunction (40.9%, n = 9), hand-foot skin reaction (31.8%, n = 7) and pains of head and four limbs (22.7%, n = 5). Two patients with grade 3 adverse events in study group were stopped continuing to use the sorafenib. Three patients with the dose of 400 mg twice daily and 17 patients with the dose reduction of sorafenib continued to the study endpoint. CONCLUSION: Patients with HCC undergoing liver transplantation could get the benefits of Sorafenib in reducing the incidence of tumor recurrence and extending disease-free and overall survival time.


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Adolescent , Adult , Aged , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Cohort Studies , Female , Humans , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Liver Transplantation , Middle Aged , Niacinamide/therapeutic use , Retrospective Studies , Sorafenib , Treatment Outcome , Young Adult
11.
Colloids Surf B Biointerfaces ; 100: 163-8, 2012 Dec 01.
Article in English | MEDLINE | ID: mdl-22766293

ABSTRACT

While granulysin has been suggested to play an important role in adaptive immune responses against bacterial infections by killing pathogens, and molecular force for protein-protein interaction or protein-bacteria interaction may designate the specific functions of a protein, the molecular-force basis underlying the bacteriolytic effects of granulysin at single-molecule level remains unknown. Here, we produced and purified bactericidal domain of macaque granulysin (GNL). Our bacterial lysis assays suggested that GNL could efficiently kill bacteria such as Listeria monocytogenes. Furthermore, we found that the interaction force between GNL and L. monocytogenes measured by an atomic force microscopy (AFM) was about 22.5 pN. Importantly, our AFM-based single molecular analysis suggested that granulysin might lyse the bacteria not only through electrostatic interactions but also by hydrogen bonding and van der Waals interaction. Thus, this work provides a previous unknown mechanism for bacteriolytic effects of granulysin.


Subject(s)
Anti-Bacterial Agents/chemistry , Antigens, Differentiation, T-Lymphocyte/chemistry , Listeria monocytogenes/drug effects , Aluminum Silicates/chemistry , Animals , Anti-Bacterial Agents/pharmacology , Antigens, Differentiation, T-Lymphocyte/pharmacology , Bacteriolysis , Cells, Immobilized , Colony Count, Microbial , Escherichia coli/genetics , Hydrogen Bonding , Listeria monocytogenes/growth & development , Macaca , Microscopy, Atomic Force , Perforin/pharmacology , Protein Structure, Tertiary , Recombinant Proteins/chemistry , Recombinant Proteins/pharmacology , Static Electricity
12.
Zhonghua Wai Ke Za Zhi ; 50(3): 222-5, 2012 Mar.
Article in Chinese | MEDLINE | ID: mdl-22800744

ABSTRACT

OBJECTIVE: To investigate the clinical characteristics, diagnosis and treatment of digestive tract leakage after orthotopic liver transplantation (OLT). METHODS: Sixty-one recipients had digestive tract leakage in early stage after OLT among 1173 cases from January 2000 to December 2010. There were 55 male and 6 female patients, aging from 36 to 61 years, with a median of 45 years. Digestive tract leakage included bile leakage (46 cases), gastric leakage (5 cases), duodenal leakage (1 case), jejunal leakage (4 cases), ileal leakage (1 case) and colon transversum leakage (4 cases). Ten of recipients with gastrointestinal leakage had 1 to 3 times of abdominal surgery before OLT. Abdominal drainage was used in 28 cases with bile leakage, and additionally, endoscopic retrograde cholangiopancreatography, endoscopic nasobiliary drainage and stenting were performed for 8 of them, and surgical neoplasty for another 18 patients with bile leakage. Simple surgical neoplasty of perforation was performed for 13 patients with gastrointestinal leakage, and diverticulectomy and neoplasty for 1 case with duodenal leakage, and partial jejunostomy for one severe jejunal leakage. Nutritional support was administered for all of cases. RESULTS: The incidence rate of digestive tract leakage in early stage after OLT was 5.20% (61/1173). Intra-operative iatrogenic injury of gastrointestinal tract was occurred in 6 cases with gastrointestinal leakage. After treatment, 11 cases died of multiple organ failure resulted from severe infection, with mortality of 18.0% (11/61), including 4 cases with bile leakage, with the mortality of 8.6% (4/46), and 7 cases with gastrointestinal tract leakage, with the mortality of 46.6% (7/15). The remanent 50 cases through comprehensive treatment with a span of 1 to 3 months recovered and discharged healthily. No digestive tract leakage reoccurred in the follow-up of 6 to 84 months. CONCLUSIONS: The morbidity of digestive tract leakage in early stage after OLT is low, but its mortality is high, especially for gastrointestinal tract leakage. High dose corticosteroids therapy, history of abdominal operation and intra-operative iatrogenic injury may be high risk factor. Comprehensive treatment is crucial for improving prognosis.


Subject(s)
Digestive System Fistula/therapy , Liver Transplantation/adverse effects , Postoperative Complications/therapy , Adult , Digestive System Fistula/diagnosis , Digestive System Fistula/etiology , Drainage , Female , Humans , Male , Middle Aged , Postoperative Complications/diagnosis
13.
Exp Clin Transplant ; 10(3): 258-62, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22631063

ABSTRACT

OBJECTIVES: To investigate the efficacy and safety of an immunosuppressive regimen of steroid avoidance in combination with induction therapy and tacrolimus in liver transplant recipients. MATERIALS AND METHODS: Eighty-two adult liver transplant recipients were randomized into 2 groups: standard protocol group (n=41) in which steroids were withdrawn 3 months after the operation, and a 24-hour steroid avoidance group (n=41) in which steroids were eliminated within 24 hours. The incidence of acute rejections, infections (bacterial, fungal, and cytomegalovirus), and metabolic complications were analyzed between the groups. RESULTS: The incidence of early posttransplant diabetes mellitus and the average dosage of insulin consumption among diabetic recipients were significantly higher in recipients in the standard protocol group than in the 24-hour avoidance group (P < .05). In addition, the incidence of hypertension and infection during the follow-up were also higher in patients of the standard protocol group (P < .05). The incidence of hypertension in the early posttransplant period, hyperlipemia, and acute rejection during the follow-up were comparable between the groups (P > .05). CONCLUSIONS: Twenty-four hour steroid avoidance combined with induction therapy and tacrolimus maintenance is a safe and efficient immunosuppression strategy that can significantly reduce posttransplant infections and other complications owing to long-term use of steroids, without increasing the risk of acute rejection.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Liver Transplantation/immunology , Recombinant Fusion Proteins/therapeutic use , Steroids/therapeutic use , Tacrolimus/therapeutic use , Withholding Treatment , Adult , Aged , Basiliximab , China , Diabetes Mellitus/epidemiology , Drug Therapy, Combination , Female , Follow-Up Studies , Graft Rejection/epidemiology , Humans , Hypertension/epidemiology , Incidence , Kaplan-Meier Estimate , Liver Transplantation/mortality , Male , Middle Aged , Risk Factors , Time Factors
14.
Hepatobiliary Pancreat Dis Int ; 11(2): 137-42, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22484580

ABSTRACT

BACKGROUND: Steroids have been the mainstay of immunosuppressive regimen in liver transplantation. However, the use of steroids is associated with various post-transplant complications. This study evaluated the efficacy and safety of reduced immunosuppressive regimen with steroids (steroid elimination within 24 hours post-transplant) in a cohort of Chinese liver transplant recipients. METHODS: Seventy-six patients in line with the selection criteria were enrolled in this prospective study. All patients received anti-IL-2 receptor antibody induction and tacrolimus-based maintenance therapy. The recipients were divided into two groups according to the duration of steroid use: 40 transplant in a 3-month withdrawal group and the remaining 36 in a 24-hour elimination group. Recipient survival, post-operative infections, biopsy-proven acute rejection and steroid-resistant acute rejection, non-healing wound, recurrence of hepatitis B virus (HBV) and hepatocellular carcinoma (HCC), de novo diabetes, hyperlipidemia and hypertension were assessed in the two groups. RESULTS: There was no significant difference in patient survival, incidence of acute rejection episodes and hyperlipidemia, and recurrence of HBV and HCC between the two groups. However, the incidence rates of post-transplant infection, non-healing wound, de novo diabetes and hypertension were significantly lower in the 24-hour elimination group than in the 3-month withdrawal group (all P values <0.05). CONCLUSION: Under anti-IL-2 receptor antibody induction and tacrolimus-based maintainance, steroid elimination within 24 hours post-transplant is associated with reduced steroid-related complications without increasing the risk of rejection.


Subject(s)
Graft Rejection/immunology , Graft Rejection/prevention & control , Liver Transplantation/immunology , Steroids/adverse effects , Steroids/therapeutic use , Withholding Treatment , Antibodies, Anti-Idiotypic/adverse effects , Antibodies, Anti-Idiotypic/therapeutic use , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , China , Follow-Up Studies , Hepatitis B/epidemiology , Hepatitis B/mortality , Hepatitis B/surgery , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Incidence , Liver Neoplasms/epidemiology , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Liver Transplantation/mortality , Prospective Studies , Receptors, Interleukin-2/immunology , Recurrence , Survival Rate , Tacrolimus/adverse effects , Tacrolimus/therapeutic use , Time Factors , Treatment Outcome
15.
Exp Clin Transplant ; 10(2): 132-5, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22432756

ABSTRACT

OBJECTIVES: To evaluate the efficacy and safety of conversion from calcineurin inhibitors to sirolimus among liver transplant recipients with calcineurin inhibitor-induced complications. MATERIALS AND METHODS: After receiving liver transplants, 25 patients with calcineurin inhibitor-induced complications (22 renal dysfunction and 3 new-onset diabetes mellitus) were converted from sirolimus to tacrolimus. The serum creatinine, sirolimus trough level, liver function, acute rejection episodes, and drug-related adverse effects were monitored. RESULTS: The patients were followed for 12 to 50 months (median, 25 months). The renal function of the 22 patients with renal dysfunction improved after sirolimus conversion. The serum creatinine levels were significantly lower at 3 months after conversion versus before conversion (113.2 ± 21.8 µmol/L vs 163.2 ± 45.3 µmol/L; P < .05). At the end of the follow-up, the average serum creatinine level was 101.9 ± 23.4 µmol/L among the 20 living recipients. Diabetes also was under control in 3 diabetic recipients after the conversion. Four patients experienced episodes of acute rejection, and intravenous steroid bolus therapy was administered in 2 of them. No graft was lost because of acute rejection. The adverse effects of sirolimus included hyperlipidemia (7/25), anemia (8/25), and mouth ulcers (9/25). All these adverse effects were relieved after a short-term symptomatic therapy, and no patient was withdrawn from the conversion trial. CONCLUSIONS: Sirolimus monotherapy is effective and safe in liver transplant recipients. Conversion to sirolimus was associated with a sustained improvement in renal function and diabetes mellitus without an increased incidence of acute rejection episodes.


Subject(s)
Calcineurin Inhibitors , Graft Rejection/drug therapy , Liver Transplantation , Sirolimus/administration & dosage , Tacrolimus/adverse effects , Acute Disease , Anemia/chemically induced , Creatinine/blood , Diabetes Mellitus, Type 2/chemically induced , Follow-Up Studies , Humans , Hyperlipidemias/chemically induced , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Oral Ulcer/chemically induced , Retrospective Studies , Sirolimus/adverse effects , Tacrolimus/administration & dosage
16.
World J Gastroenterol ; 18(7): 646-53, 2012 Feb 21.
Article in English | MEDLINE | ID: mdl-22363135

ABSTRACT

AIM: To observe the synergistic effects of hyperthermia in oxaliplatin-induced cytotoxicity in human colon adenocarcinoma Lovo cells. METHODS: The human colon adenocarcinoma cell line Lovo was obtained from Sun Yat-Sen University. Cells were sealed with parafilm and placed in a circulating water bath, and was maintained within 0.01 °C of the desired temperature (37 °C, 39 °C, 41 °C, 43 °C and 45 °C). Thermal therapy was given alone to the negative control group while oxaliplatin was administered to the treatment group at doses of 12.5 µg/mL and 50 µg/mL. Identification of morphological changes, 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and Western blotting were used to investigate the effect of thermochemotherapy on human colon adenocarcinoma Lovo cells, including changes in the signal pathway related to apoptosis. RESULTS: A temperature-dependent inhibition of cell growth was observed after oxaliplatin exposure, while a synergistic interaction was detected preferentially with sequential combination. Thermochemotherapy changed the morphology of Lovo cells, increased the inhibition rate of the Lovo cells (P < 0.05) and enhanced cellular population in the G0/G1 phase (16.7% ± 4.8 % in phase S plus 3.7% ± 2.4 % in phase G2/M, P < 0.05). Thermochemotherapy increased apoptosis through upregulating p53, Bax and downregulating Bcl-2. Protein levels were elevated in p53, Bax/Bcl-2 in thermochemotherapy group as compared with the control group (P < 0.05). CONCLUSION: Thermochemotherapy may play an important role in apoptosis via the activation of p53, Bax and the repression of Bcl-2 in Lovo cells.


Subject(s)
Antineoplastic Agents/therapeutic use , Colonic Neoplasms/pathology , Colonic Neoplasms/therapy , Hyperthermia, Induced/methods , Organoplatinum Compounds/therapeutic use , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Colonic Neoplasms/metabolism , Humans , Organoplatinum Compounds/pharmacology , Oxaliplatin , Proto-Oncogene Proteins c-bcl-2/metabolism , Tumor Suppressor Protein p53/metabolism , bcl-2-Associated X Protein/metabolism
17.
Zhonghua Yi Xue Za Zhi ; 92(44): 3143-6, 2012 Nov 27.
Article in Chinese | MEDLINE | ID: mdl-23328429

ABSTRACT

OBJECTIVE: To investigate the roles of E-cadherin (E-cad) in enhancing the in vitro differentiation of hepatocytes from murine embryonic stem cells (ESCs). METHODS: Exogenous E-cad was transfected into BALB/c murine ESCs to enable its stable expression. Then hepatic differentiation from E-cad-ESCs was induced by such growth factors as hepatocyte growth factor (HGF), fibroblast growth factor (FGF) and transforming growth factor (TGF). And the expressions of hepatic markers ALB, TAT, Cyp7a1 and urea were detected. The morphology of hepatic differentiation was observed under microscopy. RESULTS: E-cad expression gradually decreased in normal ESC differentiation, but was stably expressed in E-cad-ESCs. In E-cad-ESC group, hepatic markers ALB, TAT and CYP7a1 were expressed earlier or higher than that in normal ESC group, and the concentrations of ALB and urea were significantly higher than that in normal ESC group. The adhesion of the differentiated E-cad-ESCs was significantly enhanced compared with the normal ESCs. They maintained close connections and multidimensional growth. Cell number of hepatocytes from ESC increased significantly in E-cad-ESC group. CONCLUSION: E-cad enhances the hepatic differentiation of ESC by increasing the number of differentiated cells and increasing the synthetic capacity of ALB and urea.


Subject(s)
Cadherins/genetics , Cell Differentiation , Embryonic Stem Cells/cytology , Hepatocytes/cytology , Animals , Cells, Cultured , Mice , Mice, Inbred BALB C , Reverse Transcriptase Polymerase Chain Reaction , Transfection
18.
Zhonghua Yi Xue Za Zhi ; 91(22): 1529-32, 2011 Jun 14.
Article in Chinese | MEDLINE | ID: mdl-21914364

ABSTRACT

OBJECTIVE: To investigate the feasibility and management of retransplantation for diffuse biliary strictures occurring after initial liver transplantation. METHODS: The clinical data of 53 consecutive liver retransplantation patients at our hospital from January 2001 to December 2009 were collected and analyzed retrospectively. Among them, 20 (37.7%) were due to diffuse biliary strictures. RESULTS: Diffuse biliary strictures appeared at 3 - 16 months after initial transplantation. The mean time was 6.3 months. The specific types included intra-hepatic diffuse biliary strictures (n = 16) and multi-strictures involving both intra- & extra-hepatic biliary ducts (n = 4). Retransplantation was performed after a failure of intervention or/and other comprehensive treatments. Among them, 14 were cured and 6 died from peri-operative complications including serious abdominal infection & MODS (multiple organ dysfunction syndrome) (n = 3, 50%), biliary fistula (n = 2, 33.3%) and hepatic artery embolism (n = 1, 16.7%). These patients were followed up for a mean time of 1.8 years (range: 1 - 5 years). The accumulative survival rates at 1, 3 and 6 months were 80.0%, 75.0% and 70.0% respectively. CONCLUSIONS: Liver retransplantation is the ultimate treatment for diffuse biliary strictures after liver transplantation. The survival rate is associated with operative timing, surgical techniques and peri-operative management.


Subject(s)
Bile Duct Diseases/surgery , Liver Transplantation/methods , Postoperative Complications/surgery , Adult , Aged , Bile Duct Diseases/etiology , Bile Ducts, Intrahepatic/pathology , Constriction, Pathologic , Female , Humans , Male , Middle Aged , Reoperation , Retrospective Studies , Survival Rate , Young Adult
19.
Zhonghua Wei Chang Wai Ke Za Zhi ; 14(3): 199-201, 2011 Mar.
Article in Chinese | MEDLINE | ID: mdl-21442484

ABSTRACT

OBJECTIVE: To investigate the effect of Campath-1H induction on immunosuppression in small intestine transplantation. METHODS: Clinical data of a patient who underwent small intestine transplantation were retrospectively summarized. RESULTS: Intraoperative Campath-1H induction by intravenous injection was administered. Triple immunosuppression(FK506, MMF and methylprednisolone) was used postoperatively. The lymphocyte and leukocyte decreased significantly following Campath-1H induction, and returned to normal after adjusting the dose of immunosuppressant and use of colony stimulating factor. There were no acute rejection, graft versus host disease, or severe infection during the immediate postoperative period. The patient recovered and discharged. CONCLUSION: Intraoperative Campath-1H induction and postoperative triple immunosuppression using FK506, MMF, and methylprednisolone may prevent rejection and graft versus host disease in the early stage after small intestine transplantation.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Immunosuppression Therapy , Immunosuppressive Agents/therapeutic use , Intestine, Small/transplantation , Adult , Alemtuzumab , Graft Rejection/prevention & control , Humans , Male , Retrospective Studies
20.
Zhonghua Yi Xue Za Zhi ; 91(42): 2977-80, 2011 Nov 15.
Article in Chinese | MEDLINE | ID: mdl-22333023

ABSTRACT

OBJECTIVE: To explore the resistance rate, risk factors and mortality of Escherichia coli bloodstream infections (BSI) after liver transplantation. METHODS: From January 1993 to May 2010, a retrospective analysis of Escherichia coli in liver transplants were conducted. RESULTS: A total of 88 BSI occurred in 83/695 patients and Escherichia coli (n = 23) was most commonly found. Carbapenem and piperacillin-tazobactam were the most consistently active against Escherichia coli while the resistance rate to enterococcus for ciprofloxacin, gentamycin, ampicillin-clavulanic acid was over 60%. Univariate analysis identified the following variables as risk factors for Escherichia coli bacteremia: cholangioenterostomy (P < 0.001) and ductal complications (P < 0.001). Escherichia coli bloodstream infection could increase the mortality at 15 days after bloodstream infection. No significant difference in mortality occurred at 30 days and 1 year after enterococcal bacteremia. CONCLUSION: Escherichia coli after liver transplantation is resistant to agents but commonly active to carbapenem and piperacillin-tazobactam. The risk factor associated with Escherichia coli bloodstream infections are cholangioenterostomy and ductal complications. Escherichia coli bloodstream infection can increase the mortality at 15 days after bloodstream infection.


Subject(s)
Bacteremia/mortality , Drug Resistance, Bacterial , Escherichia coli Infections/mortality , Escherichia coli/drug effects , Liver Transplantation/adverse effects , Anti-Bacterial Agents/pharmacology , Bacteremia/etiology , Escherichia coli Infections/etiology , Female , Humans , Male , Retrospective Studies , Risk Factors , Survival Rate
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