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 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 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 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 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.