Mycophenolate mofetil and sirolimus in hepatocyte transplantation in an experimental model of toxic acute liver failure.

INTRODUCTION: Hepatocyte transplantation is proposed as a solution for liver failure. The allotransplantation of hepatocytes has been studied extensively, however, graft rejection remains a major problem. The aim of the present study was to evaluate the immunosuppressive activity of mycophenolate mofetil (MMF), sirolimus, and their combination in an experimental model of hepatocyte allotransplantation in rats with acute liver failure. MATERIALS AND METHODS: Five male Wistar rats were used as hepatocyte donors and 60 male Lewis rats as recipients. The recipients were divided into five groups of 12 animals each. Group 1: no treatment. Group 2: cyclosporine. Group 3: sirolimus. Group 4: MMF. Group 5: MMF and sirolimus. All surviving animals were preserved for 15 days. For the induction of acute liver failure the recipients were injected with N-dimethyl-nitrosamine 24 hr before transplantation. The isolated hepatocytes were transplanted intrasplenically. RESULTS: Analysis of the results showed a statistically significant prolongation of animal survival for groups 3, 4, and 5. More animals in group 5 survived than those in groups 3 and 4, although the difference was not statistically significant. Transplant hepatocyte survival was significantly better in groups 3, 4, and 5. Hepatocytes transplanted in the spleen of animals of group 5 showed better survival compared with those of groups 3 and 4. CONCLUSION: Use of MMF and sirolimus, as monotherapy or in combination, is both effective and safe as immunosuppressive treatment in hepatocyte transplantation, as was proven in this experimental protocol.

A new pancreaticojejunostomy technique: a battle against postoperative pancreatic fistula.

AIM: To present a new technique of end-to-side, duct-to-mucosa pancreaticojejunostomy with seromuscular jejunal flap formation, and insertion of a silicone stent. METHODS: We present an end-to-side, duct-to-mucosa pancreaticojejunostomy with seromuscular jejunal flap formation, and the insertion of a silicone stent. This technique was performed in thirty-two consecutive patients who underwent a pancreaticoduodenectomy procedure by the same surgical team, from January 2005 to March 2011. The surgical procedure performed in all cases was classic pancreaticoduodenectomy, without preservation of the pylorus. The diagnosis of pancreatic leakage was defined as a drain output of any measurable volume of fluid on or after postoperative day 3 with an amylase concentration greater than three times the serum amylase activity. RESULTS: There were 32 patients who underwent end-to-side, duct-to-mucosa pancreaticojejunostomy with seromuscular jejunal flap formation. Thirteen of them were women and 19 were men. These data correspond to 40.6% and 59.4%, respectively. The mean age was 64.2 years, ranging from 55 to 82 years. The mean operative time was 310.2 ± 40.0 min, and was defined as the time period from the intubation up to the extubation of the patient. Also, the mean time needed to perform the pancreaticojejunostomy was 22.7 min, ranging from 18 to 25 min. Postoperatively, one patient developed a low output pancreatic fistula, three patients developed surgical site infection, and one patient developed pneumonia. The rate of overall morbidity was 15.6%. There was no 30-d postoperative mortality. CONCLUSION: This modification appears to be a significantly safe approach to the pancreaticojejunostomy without adversely affecting operative time.

Epidemiology, clinical data, and treatment of viral hepatitis in a large cohort of intravenous drug users.

OBJECTIVES: The aim of this study was to evaluate retrospectively the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, epidemiological parameters, and the clinical data from the antiviral treatment of hepatitis C in a large cohort of intravenous drug users (IDUs) followed-up from 1994 until 2008. PATIENTS AND METHODS: A total of 1179 former IDUs followed up either in the liver unit or in the context of a substitution program organization were included in this study. A retrospective chart review was prepared to retrieve data on the patients' demographic characteristics, the prevalence of viral hepatitis, and information on HCV treatment. RESULTS: The prevalence of HBsAg positive was 5%. A substantial number of patients were anti-HCV positive (847/1170, 73%), 189 were lost to follow-up, 526 (80%) were HCV RNA positive and 132 (20%) had a self-limited disease. The most prevalent genotype was 3 (59.7%). Twenty-five percent of the study population received antiviral treatment against HCV infection. Patients seen in the Liver Unit were more likely to receive antiviral treatment. The sustained virological response (SVR) was 80% with patients treated with pegylated interferon and ribavirin having a significantly higher SVR rate. CONCLUSIONS: Our results show that (a) the majority of IDUs in Greece have chronic hepatitis C and the prevalent genotype is 3 (b) patients who complete therapy have SVR rates similar to those without drug-dependence, and (c) since IDUs constitute the core of the hepatitis C epidemic and the main route of HCV transmission, efforts to treat these patients should be made.

Prognostic impact of DNA ploidy pattern, S-phase fraction (SPF), and proliferating cell nuclear antigen (PCNA) in patients with primary gastric lymphoma.

BACKGROUND: DNA ploidy, S-phase fraction (SPF), and proliferating cell nuclear antigen (PCNA) are considered to be significant prognostic factors in non-Hodgkin lymphomas. However, reports on their prognostic importance in gastric lymphoma patients are relatively lacking. METHODS: In the present study, we retrospectively studied the above-mentioned parameters in 29 patients with primary gastric lymphoma; 11/29 had B-low grade mucosa associated lymphoid tissue lymphoma (B-MALT), while 18/29 had diffuse large B-cell lymphoma (DLBCL), according to WHO classification. Proliferative activity was studied by staining against PCNA; in addition, the prognostic significance of DNA ploidy and SPF, as determined by flow cytometry, were investigated and compared to the results of the PCNA stainings. RESULTS: Seven out of 29 patients were found to have aneuploid tumors; DNA index values were >1 for all aneuploid lymphomas. There was no difference in DNA aneuploidy in MALT vs. DLBCL. The mean percentage of SPF was 11.4. SPF was found significantly lower in MALT vs. DLBCL (P < 0.05). The mean percentage of PCNA positive tumor cells was 52.6. PCNA protein expression was significantly lower in MALT vs. DLBCL (P < 0.0001). There was a significant positive correlation between PCNA score and SPF (P < 0.01, by Spearman analysis). DNA ploidy had no impact on survival in the present study. Both SPF and PCNA expression were important prognostic factors in the univariate analysis; however, in the multivariate analysis, the only independent prognostic factor for survival was PCNA expression. CONCLUSIONS: These findings indicate that SPF and PCNA are significant prognostic factors in patients with primary gastric lymphomas. However, in the present study, DNA ploidy had no impact on survival in patients with primary gastric lymphomas.