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 evaluate the impact of steatotic hepatic grafts on postoperative early liver function and prognosis.Methods Clinical data of 35 cases receiving steatotic liver grafts in our hospital were retrospectively analyzed.The donor liver grafts were divided into 3 groups based on the degree of fatty infiltration(＜20%group,20%～40%group,≥40%group).Results were compared with that from control normal grafts(41 cases).Liver function parameters including AST,ALT,TB,PT on the day of surgery and 1,2,3,7 days later were monitored among the 4 groups,as well as the incidence of delayed nonfunction (DNF),and 3 and 6 months patient survival rate.Analysis of the correlation between degree of donor steatosis and liver function after operation was carried out.Resuits There was significant difference in postoperative ALT、AST、TB、PT level between≥40%group and 20%～40%group,and between 20%～40%and group＜20%group.There was no significant difference among the groups in DNF occurrence rate and 3 month.6 month patient survival rate.Correlation analysis suggested that the degree of donor steatosis was positively correlated with the damage of liver function.Conclusions Grafts with≤20% steatosis was safe,whereas≥20% especially ≥40% steatosis carries a high risk of posttransplant liver dysfunction even delayed nonfunction.

Objective To investigate the diagnosis,and management of aspergillosis infection in orthotopic liver transplant recipients.Methods The clinical data of 776 cases of orthotopic liver transplantation patients from 2000 to 2006 were collected and analyzed retrospectively.Results Aspergillosis infection occurred in 13 patients(1.68%),among those there were pulmonary aspergillus infection in 7 cases,hepatic aspergillus infection in 2,cerebral aspergillosis in one and multi-organ aspergillosis in 3.Liposomal amphotericin B was the main therapy especially for cases at early stage.7 patients died of aspergillosis and the aspergillosis-related mortality was 53.8%.Conclusion Early diagnosis and management remain the key for the prevention and cure for aspergillus infection and decreasing mortality.The use of anti-fungal therapy should follow the principle of eliminating the local infection,adjusting immunosuppressive regimen and use of sensitive anti-fungal drugs.Anti-fungal drugs should be started early,with sufficient dosage and long-term.

Objective To evaluate the surgical techniques and short-term clinical results of simultaneous pancreaticoduodenum-kidney transplantation(SPK)with the enteric drainage(ED)of exocrine secretions of the pancreas.Method From Jan 2005 to Jun 2009,ten diabetic patients with uremia diabetes underwent SPK.The pancreas graft was placed intraperitoneally with exocrine secretions drained into the proximal iejunum by side-to-side anastomosis.The multivisceral cluster grafts(liver,kidney,pancreas and duodenum)were procured after simultaneously rapid perfusion with cool UW solution through donor's abdominal aorta and superior mesenterie vein in 10 no heart beating cadeveric donors.Quadruple immunosuppressive therapy with anti-CD25 monoclonal antibody,tacrolimus,mycophenolate mofetil and steroids was adopted.Results SPK was successfully performed in all cases.The mean warm ischemia time of donor organ was(5.9 ±2.6)min,the mean cold ischemic time of the kidney was(5.2 ±2.2)hours and that of the pancreas was(9.3±3.6)hours.Patient and graft survival rates were 90.0% and 90% at 6 month after transplant,respectively.None of the grafts lost due to enteric or pancreatic leakage or intraabdominal infection.The most common surgical complications were wound infection(n=3),and enteric anastomostic hemorrage(n=2),which were all cured by nonoperative management.Three biopsy-proven acute renal rejection episodes occurred within 12 months postoperation,2 of them were reversed Successfully.and 1 died of cerebral complication during the recovery from continuous renal replacement therapy(CRRT)after the failure of aggressive antirejection treatment.Other patients(n=9)became insulin-free euglycemie at(9.3±3.8)day postoperatively,and are well and insulin-free at a follow-up of 6～12 months.Conclusions High quality procurement of donor grafts and suitable arterioplasty are prerequisites for a successful combination kidney and pancreas transplantation.Enteric exocrine drainage by direct side-to-side anastomosis seems to be a simple and reliable technique.

Objective To explore the causes and management of intra-abdominal hemorrhage after orthotopic liver transplantation (OLT). Methods Clinical data of 638 OLT patients were analyzed retrospectively from January 2004 to December 2008 in the First Affiliated Hospital of Sun Yat-Sen University. The diagnosis and treatment of postoperative intra-abdominal hemorrhage after OLT were reviewed. Results Among the 638 patients, 53 suffered from posttransplant intra-abdominal hemorrhage,the morbidity was 8. 3% (53/638). Thirty-one cases suffering from bleeding on raw surfaces or around the liver due to impairment of coagulation function were treated by non-surgery methods, 22 cases who suffered from active postoperative intra-abdominal hemorrhage due to surgical factors underwent laparotomy and bleeding control operation after failure of anti-shock treatments such as hemostatic drugs, blood reperfusion.Among the 53 patients who suffered from intra-abdominal hemorrhage, 12 patients died, and the main causes were serious infections and multiple organ dysfunction syndrome. The mortality associated with intraabdominal hemorrhage was 22. 6%. Conclusions Intra-abdominal hemorrhage at different locations were found after OLT, and the fatal rate is quite high. Timely and appropriate treatments especially laparotomy may improve the prosnosis of these patients.

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.