Characterizing PTP4A3/PRL-3 as the Potential Prognostic Marker Gene for Liver Hepatocellular Carcinoma.

Background: A large number of cancer-related deaths in the world can be attributed to liver hepatocellular carcinoma (LIHC). The purpose of this study is to explore protein tyrosine phosphatase type IV A member 3 (PTP4A3/PRL-3) as a new and reliable biomarker to predict the prognosis of LIHC and determine the potential therapeutic targets or drugs that can be used for treating LIHC. Methods: We included three LIHC datasets with clinical information and expression profiles from public databases. The expression level of PTP4A3 was analyzed, and based on the results, the samples were divided into high- and low-expression groups. The Kaplan-Meier survival analysis method was used to determine the relationship between PTP4A3 and prognosis. The enrichment differences among the functional pathways associated with the high- and low-expression groups were determined using the gene set enrichment analysis (GSEA) method. Five methods were used to determine the differences among the tumor microenvironment in the low- and high-expression groups. The sensitivity of the low- and high-expression groups toward different drug treatment methods was predicted by analyzing the Tumor Immune Dysfunction and Exclusion (TIDE) scores and determining the biochemical half-maximal inhibitory concentration (IC50). Results: The expression levels of the LIHC and adjacent samples were analyzed, and it was observed that the expression level of PTP4A3 in tumor tissue was significantly higher than the expression level of the same gene in the adjacent samples. It was also inferred that it might be a cancer-promoting gene. It was concluded that high-expression results in a significantly poor prognosis. The high-expression group was significantly enriched in the tumor-related pathways, such as the PI3K-AKT signaling pathway. In addition, the results obtained by conducting immune infiltration analysis revealed a significant positive correlation between some immune scores and the gene PTP4A3. The drug KIN001-135 and gene PTP4A3 were also found to correlate positively with each other. CP466722, Pyrimethamine, AKT inhibitor VIII, Embelin, Cisplatin, QS11, Bexarotene, and Midostaurin negatively correlated with PTP4A3 associated with the three datasets. Moreover, the drugs Cisplatin, QS11, Midostaurin, and CP466722 were more sensitive toward the high-expression group than the low PTP4A3 expression group. Significant differences were observed in these cases. Conclusion: PTP4A3/PRL-3 is potentially associated with the progression, metastasis, and invasion of LIHC. The prognosis of LIHC patients is negatively impacted by the high-expression levels of the gene. The results indicate that PTP4A3/PRL-3 is an important prognostic factor for LIHC and is a new potential prognostic detection target. The discovery of the 8 drugs that were negatively associated with PTP4A3 provided a new direction that can be developed in the future for the treatment of LIHC.

Revascularization of iatrogenic intraoperative injury to a major artery during hepatobiliary-pancreatic surgery: a single-center experience in China.

BACKGROUND: Although uncommon during hepatobiliary-pancreatic (HBP) surgery, iatrogenic intraoperative injury to a major artery requires prompt and appropriate repair. Here, we outline our surgical experience with the repair of this injury and compare our experience to findings garnered from a selective review of the literature. METHODS: We retrospectively analyzed the clinical diagnoses, surgical methods, sites of arterial injury, operative repair, intra-operative blood loss, blood transfusion requirements, postoperative management and outcome of 17 consecutive patients who sustained iatrogenic intra-operative injuries to major arteries during HBP surgery between January 2008 and December 2013. RESULTS: Depending on the location and extent of injury, suture repair, primary end-to-end anastomosis, artery transposition, interposition grafting, or arterio-portal shunting were used. Postoperative morbidity occurred in three cases and there was only one case of in-hospital mortality (5.9%). No arterial thrombosis or other repair-related complications were found after the operation with a follow-up duration of 6 months. CONCLUSIONS: The use of an optimal repair method for injured arteries based on their location and extent resulted in a satisfactory outcome.

Reduction of FoxP3+ Tregs by an immunosuppressive protocol of rapamycin plus Thymalfasin and Huaier extract predicts positive survival benefits in a rat model of hepatocellular carcinoma.

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.

Effect of laparoscopic splenectomy on portal vein thrombosis and serum YKL-40 in patients with cirrhotic portal hypertension.

INTRODUCTION AND OBJECTIVES: Laparoscopic splenectomy (LS) is a supportive intervention for cirrhotic patients. However, its efficacy for patients with cirrhotic portal hypertension (CPH) still needs clarification. Studies indicated YKL-40 might be effective targets for treatment of splenomegaly, however deeper insights are unclear. The aim of this study was to investigate the effect of LS on the formation of portal vein thrombosis (PVT) and serum levels of a fibrosis marker, YKL-40, in patients with CPH. MATERIALS AND METHODS: A total of 80 patients who underwent LS and 30 healthy controls were investigated in this study. Serum levels of YKL-40 were measured by enzyme-linked immunosorbent assay (ELISA). Demographic characteristics including age and gender were recorded. Clinicopathological and laboratory examinations included the severity of esophageal varices and the presence of viral hepatitis. The liver function was assessed according to the Child-Pugh classification. The incidence of PVT before and after operation was also monitored. RESULTS: Serum YKL-40 was significantly increased in CPH patients, and was associated with Child-Pugh score and HBV infection. Furthermore, elderly patients had an increased risk for postoperative PVT. Higher serum YKL-40 was observed in patients with thrombus at postoperative 7, 14 and 21 days than those without thrombus. CONCLUSIONS: LS could reduce serum YKL-40 levels and PVT progression and was a useful treatment for patients <40 years of age with CPH.

Sirolimus treatment for cirrhosis or hepatocellular carcinoma patients accompanied by psoriasis after liver transplantation: A single center experience.

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.

[Development of laparoscopic technology in biliary surgery in the past 23 years: a single-center experience].

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.