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BACKGROUND: Investigate immunoregulation and anti-tumor immunity of FoxP3+Tregs after treatment with rapamycin (RAPA/SRL) plus thymalfasin (Zadaxin) and Huaier extract (PS-T) in a hepatocellular carcinoma (HCC) rat model simulating HCC relapse after liver transplant (LT). METHODS: We successfully established a rat model simulating HCC relapse after LT using an optimized chemical induction method with TACROLIMUS, methylprednisolone, and diethylnitrosamine as identified by visible liver nodules and hematoxylin-eosin staining. The model rats were then treated with RAPA, Zadaxin, and PS-T. Immune status changes were analyzed by flow cytometry, and protein expression of Akt and mTOR was determined by western blotting. Cytokines were measured by ELISAs. RESULTS: Combined therapy by RAPA plus Zadaxin and PS-T obviously alleviated hepatic pathological changes and significantly decreased the levels of FoxP3+Tregs in peripheral blood, the spleen, and the liver (P<0.05) and expression of mTOR protein (P<0.01) in the liver, obviously improved survival time (P=0.02). Moreover, the levels of CD8+T cells were increased significantly to almost normal levels (P<0.05) in comparison with no SRL monotherapy protocols. Inhibitory cytokines were also decreased in accordance with FoxP3+Tregs. Significant decreases of IL-10 and TGF-ß were observed after SRL-based therapy (P<0.01) in comparison with the other groups. Serum alpha fetoprotein (AFP) and vascular endothelial growth factor (VEGF) levels were also decreased significantly (P<0.05). FoxP3+Tregs showed a negative correlation with CD8+ and CD4+/CD8+T cells and a positive correlation with AFP, and VEGF (P<0.05). CONCLUSIONS: SRL-based therapy reduces FoxP3+Tregs to decrease secreted inhibitory cytokines which may enhancement the viability and number of CD8+T cells to exert anti-tumor effects that are mainly mediated through the AKT-mTOR signaling pathway.
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There is currently no consensus on the most suitable therapeutic approach for psoriasis (PS) co-existing with posthepatic cirrhosis (PCs) and hepatocellular carcinoma (HCC) following liver transplantation (LT). The present study provides an analysis of the therapeutic experience of such patients. Five LT recipients (two with PC and three with HCC) with accompanying PS were included. The induction program consisted of methylprednisolone plus basiliximab treatment. The initial postoperative treatment scheme consisted of tacrolimus (FK506) plus mycophenolate mofetil (MMF) and hormone; the latter was withdrawn 1 week after LT. The patients with PC had been using FK506 with or without a postoperative MMF program; the patients with HCC and recurrence of PS had been switched to a sirolimus (SRL)-based replacement therapy. Furthermore, all patients received anti-hepatitis B virus (HBV) therapy. The patients were followed up after 8.3±1.5 years. There was a positive correlation between HBV-DNA copy numbers, and psoriatic area and severity index (PASI) scores (r=0.97; P=0.006). The PASI scores were decreased significantly at 6 months following surgery compared with pre-transplantation (P<0.05). The patients who had received the FK506-based treatment experienced PS recurrence two years post-transplantation. The PASI scores increased significantly (P<0.05) and then declined gradually, maintaining a stable level (P<0.05) by 1 year after switching to the SRL-based treatment. The patients who had received the SRL-based treatment exhibited no recurrence of PS. The results of the present study suggest that SRL therapy provides a promising novel treatment method for patients with PS following LT that may be superior to tacrolimus treatment. When co-existing HBV is present pre-transplantation, regular injection of human hepatitis B immunoglobulin should be used to prevent the HBV from relapsing or aggravating the PS.
RESUMO
OBJECTIVE: To summarize the 23-year experience of laparoscopic biliary surgery in General Hospital of PLA and evaluate the application of laparoscopic surgery in the treatment of biliary diseases. METHODS: We retrospectively analyzed the clinical data of 11 419 consecutive patients with biliary diseases undergoing laparoscopic surgery from April, 1992 and December, 2014. The disease spectrum was compared between patients treated before December 31, 2003 and those treated after the time point. RESULTS: The 11419 patients receiving laparoscopic surgery accounted for 56.3% of the total patients undergoing biliary surgeries during the 23 years, including 4701 male and 6718 female patients with a mean age of 50.9∓13.2 years (6-93 years). Most (80.83%) of the patients received laparoscopic surgery for gallbladder stones, and 12.53% patients had the operation for gallbladder polyps. The laparoscopic operation rate was 84.81% in patients with gallbladder stones and 34.91% in patients with extrahepatic bile duct stones, but remained low in patients with biliary carcinoma. In laparoscopic operations, laparoscopic cholecystectomy was the most frequent (96.18%) followed by operations for extrahepatic bile duct stones, in which primary suture accounted for 1.38%, traditional T tube drainage for 0.90% and laparoscopic transcystic duct exploration for 0.72%. For malignant tumors, laparoscopic technique was used mainly for the purpose of exploration (0.34%). The application of laparoscopic technique in biliary surgery tended to increase after the year 2004, especially for benign gallbladder diseases and extrahepatic bile duct stones (P<0.05). CONCLUSION: Laparoscopic technique in biliary surgery is gradually replacing the traditional open operation and becomes the gold standard for the treatment of benign biliary diseases.