Dose-Response Relationship, Drug ; Enzymes ; adverse effects ; Humans ; Hypersensitivity ; Occupational Diseases ; chemically induced ; Occupational Exposure ; adverse effects

Objective Sirolimus is a new, potent immunosuppreasant considered to be nonnephrotoxic. There is limited experience with the use of sirolimus in liver transplant recipients. This study was to investigate the clinical experience of conversion from tacrolimus-based to sirolimus-based immunosuppression in liver transplant recipients. Patients switched to cyclosporine-based immunosuppression during the same period were also enrolled as controls. Methods This retrospective study examined liver transplant recipients who had been switched from tacrelimus-based to sirolimus-based or cyelosporine-based immunosuppressive therapy between January 2004 and January 2008 in the First Affiliated Hospital of Sun Yat-sen University. Patients were divided into 2 groups: those switched to sirolimus-based immunosuppression (group A; n=32); and those switched to cyclosporine-based immunosuppression (group B; n=15). Results The rate of successful conversion was 34.5% in group A (10/32) compared with 45.5% in group B (7/15); this difference was not statistically significant (P>0.05). After conversion, renal function in patients in group A remained normal, while the renal function in patients in group B become abnormal 4 months after conversion (P<0.05). In group A, some simlimus-associated adverse effects occurred but were mild and easy to control. Conclusion Sirolimus can be used safely in place of tacrolimus in liver transplant recipients.

BACKGROUND: Tumor recurrence in liver transplant recipients greatly affects prognosis of liver transplantation with hepatocellular carcinoma (HCC). How to prevent tumor recurrence has aroused increasing attention. Arsenious acid chemotherapy is considered effective on treating moderate or advanced liver cancer, but its utilization following liver transplantation remains few. OBJECTIVE: To explore the role of arsenious acid on tumor recurrence in liver transplant patients with primary HCC extending Milan criteria. RESULTS AND CONCLUSION: All patients were routinely followed up for 3-32 months. Thirty recipients were presented with tumor recurrence, 16 in the chemotherapy group and 14 in the non-chemotherapy group. Tumor recurred in lung, liver graft and bones in most cases. The total recurrence rate was similar in these two groups, but chemotherapy could delay recurrence after transplantation (P=0.026). There was no significance in 6-month, 1-year survival rate between two groups, but the 2-year survival in the chemotherapy group was higher (P=0.037); 6-month tumor-free survival rates in the two groups had no significance, 1-year and 2-year tumor-free in the chemotherapy group were significantly higher than those in the non-chemotherapy group (P=0.030, 0.023). Intravenous arsenious acid chemotherapy can delay tumor recurrence and prolong survival in liver transplant patients with HCC extending Milan criteria.

This study was purpose to investigate the expression levels of HSP70 and MDR1 genes under heat shock and/or adriamycin (ADM) chemotherapy stimulation. The K562 cells were bathed in water at 43 degrees C for 1 hour, then the heat-treated K562 cells were collected and were cultured at 37 degrees C. The expression of HSP70 was assayed by immunocytochemistry, the growth suppression rate of K562 cells was detected by MTT assay, the function of P-gp and the expressions of HSP70 mRNA, MDR1 mRNA were detected by flow cytometry and real-time quantitative PCR (RT-PCR) respectively. The results showed that (1) the synthesis of HSP70 protein in K562 cells treated with high shock (43 degrees C) reached to high level after culture at 37 degrees C for 2 hours, and moved from cytoplasm to nucleolus, the expression of HSP70 began to decrease following 3 hours of culture at 37 degrees C, and gradually reached to normal level after culture at 37 degrees C for 5 hours, the location of HSP70 expression returned to cytoplasm; (2) the expressions of HSP70 mRNA and MDR1 mRNA increased following 43 degrees C heat shock, and were 4 and 5.8 times higher than that of control group at 37 degrees C culture for 2 hours respectively; (3) the expression of P-gp was higher in ADM group than that in control. The expressions of HSP mRNA and MDR1 mRNA increased significantly in heat shock plus ADM group and ADM group as compared with control (p<0.01). It is concluded that the heat shock and ADM chemotherapy both induce over expression of HSP70 and MDR1 which can maintain stability of K562 cells and may be related to formation of the MDR in leukemia.
ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Antibiotics, Antineoplastic ; pharmacology ; Cell Proliferation ; Doxorubicin ; pharmacology ; HSP70 Heat-Shock Proteins ; metabolism ; Heat-Shock Response ; Humans ; K562 Cells ; RNA, Messenger ; metabolism

Objective To analyze the surgical procedure and effect of living-related small bowel transplantation(LR-SBTx) on intestinal function failure caused by short bowel syndrome.Methods A boy, 15 years of age with short gut syndrome, who had only 8 cm of residual small intestine, associated with serious malnutrition and poor D-xylase absorption test (0.226/5h). The donor was the boy's mother. They had a match of 4 loci in HLA. In the first stage of the surgical procedure, 120 cm of ileum from the patient′s mother was transplanted into the recipient. Both ends of the transplanted intestine were exteriorized as stomas on the patient′s abdominal wall. The second stage of reconstruction of the intestine was carried out 6 months after his first operation. The residual small bowel of the recipient was transected, and both of its ends were respectively anastomosed end-to-side to the proximal and distal segments of the graft. The stomas of the graft were left in place. Results The donor and recipient operation went on smoothly. Acute rejection and infection of CMV developed postoperatively and were cured after treatment. The patient was followed-up for 8 months, the graft function recovered gradually postoperatively with increase of body weight. He can ingest a semifluid diet and take care of himself independently. Conclusions LR-SBTx is an effective way to treat short bowel syndrome. The reconstruction of the intestine in two stages for LR-SBTx decreased the risk of complications. Rejection and infection are important risk factors of LR-SBTx.

Objective To explore the monitoring methods for pancreatic graft function after upper abdominal cluster transplantation.Methods Analysis of the clinical data of 5 cases of successful upper abdominal(cluster) transplantation in our center.Results The patients recovered well after the operation.Endocrine and exocrine functions of all the pancreas graft returned to normal without any rejection.Conclusions Dynamic monitoring of blood glucose,C-peptide,blood insulin,blood amylase,urine amylase,amylase in abdominal drainage and duodenal tube decompression drainage,in addition to Doppler color ultrasound examination,can effectively detect the endocrine and exocrine function of the pancreas graft.

Objective To compare the effects of combined ‘en bloc' liver-pancreas transplantation (LPT) with portal vein drainage and simultaneous combined kidney-pancreas transplantation (KPT) with systemic venous drainage on the pancreatic endocrine function and related metabolism.Methods Four LPT patients and 6 KPT ones with normal hepato-renal function, good quality of life and periodic follow-up received measurement of serum insulin, insulin provocation test, fasting glucose, oral glucose tolerance test, C-peptide, glycated hemoglobin, triglyceride and total cholesterol; and their laboratory test parameters were compared and analyzed.Results In KPT group, 2-h insulin level, C-peptide level and total cholesterol level were significantly higher at 6th month, 3rd and 6th month postoperation (all P<0.05). But there was no significant difference in other parameters between the two groups at 6th month after operation.Conclusion Either KPT or LPT can achieve excellent endocrine function, carbohydrate and lipid metabolism; and the results show that portal venous drainage does not offer major metabolic advantages within 6 months after operation.

Objective To summarize the experience with salvage liver transplantation for patients with recurrent hetaptocellular carcinoma(HCC)after primary liver resection.Methods From 2004 to 2008,376 patients with HCC received liver transplantation in our single center.Among these patients,36 (9.6 %)underwent salvage liver transplantation after primary liver curative resection due to intrahepatic recurrence.There were 29 males and 7 females with the mean age of 46 years old.Sixteen received right lobectomy,10 received left lobectomy and the others received sectionectomy or segmentectomy.As a control group for comparison,we used clinical data of the 147 patients who underwent primary OLT for HCC within Milan Criteria.Results The mean interval between initial liver resection and salvage transplantation was 34.9±16.2 months(1-63 months).Intraoperative bleeding volume,transfusion volume and operative time in the salvage group were significantly different from those in control group (P<0.05).There were no significant difference in post-operative complications,tumor recurrence rate,survival rate and tumor-free survival between these two groups(P>0.05).Conclusion In comparison with primary OLT,although salvage liver transplantation would increase the operation difficulties,it still remains a good option for patients with HCC recurrence after curative resection.

ObjectiveTo summarize the clinical experience of simultaneous pancreas and kidney transplantation (SPK) after liver transplantation for patients with diabetes and uremia.MethodsThe clinical data of two patients who received SPK after liver transplantation were retrospectively analyzed.The two male patients had type 2 diabetes mellitus before liver transplantation,and suffered from endstage uremia due to diabetic nephropathy and immunosuppressant-induced toxicity.Rapid technique for combined abdominal multiple viscera procurement was performed.Kidneys,pancreas,duodenum segment and spleen were procured.Renal allograft was placed in the left iliac fossa,whereas pancreas allograft in the right iliac fossa. The pancreatic allograft exocrine secretion was drained into the proximal jejunum via a side-to-side duodenojujunostomy. Quadruple immunosuppressive regime including IL2 receptor monoclonal antibody induction,tacrolimus (Tac),mycophenolate mofetil (MMF) and steroid were used in case 1,and ATG and methylprednisolone were used in case 2.ResultsSPK was successfully applied to these two patients without serious surgical complications such as pancreatitis,graft and pancreatic fistula. The immunosuppressive regimen was based on tacrolimus with ATG induction,MMF and steroids.In the second case,serum creatinine level was decreased to the normal range within 1 week after the operation and then elevated continuously even he received empirical anti rejection treatment,Tac was tampered and rapamycin was used when the renal graft biopsy indicated drug toxicity,and creatinine level was decreased 3 weeks after the operation and recovered to the normal range at 5th week post-transplant. Both of the two patients achieved euglycemia with insulin independence about 10 days after the operation.And now these two patients have been followed up for 36 and 9 months,and the grafts function of the liver,kidney and pancreas was normal. Conclusion Immunologic reaction in patients undergoing simultaneous pancreas and kidneytransplantationafterlivertransplantationseemsmorecomplex, andareasonable immunosuppressive regimen is important to improVe the outcome.

Objective To explore the outcome and treatment for recipients with steroid-resistant acute rejection (SRAR) after liver transplantation. Methods From Jan 2004 to Dec 2007, 596 adult patients received liver transplantation in the Organ Transplantation Center, the First Affiliated Hospital of Sun Yat-Sen University,96 recipients experienced 113 episodes of acute rejection (AR)after the operation, 11 recipients had no response to conventional steroid bolus treatment, the clinical data of this group of patients was analyzed retrospectively. Results Incidence rate of AR in our single center was 16.1% (96/596), among them 9.7% (11/113) were steroid-resistant. SRAR occurred averagely on 19 d (6-72 d)after liver transplantation, 3 were controlled by OKT3 treatment, 4 were reversed by IL-2 receptor inhibitors combined with MMF. Rejection could not be reversed in 4 patients and 2 finally received retransplantation. Mortality rate associated with SRAR was 36.4% (4/11) including, one from acute liver failure, 1 from chronic liver failure, 1 from renal failure after retransplantation and 1 from pulmonary infection after OKT3 treatment. Conclusion SRAR is a severe complication with high mortality after liver transplantation, OKT3 and IL-2 receptor inhibitors are effective in only a portion of these patients.