HBV PreC interacts with SUV39H1 to induce viral replication by blocking the proteasomal degradation of viral polymerase.

Hepatitis B e antigen (HBeAg) seropositivity during the natural history of chronic hepatitis B (CHB) is known to coincide with significant increases in serum and intrahepatic HBV DNA levels. However, the precise underlying mechanism remains unclear. In this study, we found that PreC (HBeAg precursor) genetic ablation leads to reduced viral replication both in vitro and in vivo. Furthermore, PreC impedes the proteasomal degradation of HBV polymerase, promoting viral replication. We discovered that PreC interacts with SUV39H1, a histone methyltransferase, resulting in a reduction in the expression of Cdt2, an adaptor protein of CRL4 E3 ligase targeting HBV polymerase. SUV39H1 induces H3K9 trimethylation of the Cdt2 promoter in a PreC-induced manner. CRISPR-mediated knockout of endogenous SUV39H1 or pharmaceutical inhibition of SUV39H1 decreases HBV loads in the mouse liver. Additionally, genetic depletion of Cdt2 in the mouse liver abrogates PreC-related HBV replication. Interestingly, a negative correlation of intrahepatic Cdt2 with serum HBeAg and HBV DNA load was observed in CHB patient samples. Our study thus sheds light on the mechanistic role of PreC in inducing HBV replication and identifies potential therapeutic targets for HBV treatment.

Laparoscopic vs open radical resection in management of gallbladder carcinoma: A systematic review and meta-analysis.

BACKGROUND: Radical resection offers the only hope for the long-term survival of patients with gallbladder carcinoma (GBC) above the T1b stage. However, whether it should be performed under laparoscopy for GBC is still controversial. AIM: To compare laparoscopic radical resection (LRR) with traditional open radical resection (ORR) in managing GBC. METHODS: A comprehensive search of online databases, including Medline (PubMed), Cochrane Library, and Web of Science, was conducted to identify comparative studies involving LRR and ORR in GBCs till March 2023. A meta-analysis was subsequently performed. RESULTS: A total of 18 retrospective studies were identified. In the long-term prognosis, the LRR group was comparable with the ORR group in terms of overall survival and tumor-free survival (TFS). LRR showed superiority in terms of TFS in the T2/tumor-node-metastasis (TNM) Ⅱ stage subgroup vs the ORR group (P = 0.04). In the short-term prognosis, the LRR group had superiority over the ORR group in the postoperative length of stay (POLS) (P < 0.001). The sensitivity analysis showed that all pooled results were robust. CONCLUSION: The meta-analysis results show that LRR is not inferior to ORR in all measured outcomes and is even superior in the TFS of patients with stage T2/TNM Ⅱ disease and POLS. Surgeons with sufficient laparoscopic experience can perform LRR as an alternative surgical strategy to ORR.

Analysis of Thoracic Aorta Injury in 27 Road Traffic Accident Deaths.

OBJECTIVES: To analyze the characteristics of thoracic aorta injury in road traffic accidents, to provide data reference for forensic identification. METHODS: The data of 27 traffic accident death cases with thoracic aorta injury were analyzed according to relevant parameters including sex, age, mode of transportation, and thoracic aorta injury. RESULTS: Aortic injury in traffic accidents was significantly more in males than females, and 74.1% cases were in the age range of 31-70 years. The most common mode of transportation was the motorcycle, followed by electric bike, most of which crashed with trucks. Most cases were accompanied by rib fractures and lung injuries. Thoracic aorta injury was the most common in ascending aorta, followed by aortic arch and thoracic aorta. Ascending aorta injury was most likely to occur in the range of 0-<1.6 cm from the aortic valve, while it was rare over 2.6 cm. Taking the aortic valve as the reference, the most common locations of injury were the anterior semilunar valve, followed by the right posterior semilunar valve and the left posterior semilunar valve. Thoracic aortic rupture occurred in 63.0% cases, and intima and media lacerations only occurred in 37.0% cases. A few deceased had aortic diseases. CONCLUSIONS: The proximal part of the ascending aorta is prone to be injured because of the large external force of traffic accidents. The medical examiner should carefully examine the aortic injury in traffic accident deaths, and evaluate the relationship between the injury and the disease according to the condition and degree of aortic injury.

CRISPR-Cas9-based genome-wide screening identified novel targets for treating sorafenib-resistant hepatocellular carcinoma: a cross-talk between FGF21 and the NRF2 pathway.

The treatment of hepatocellular carcinoma (HCC) has been dominated by multikinase inhibitors for more than a decade. However, drug resistance can severely restrict the efficacy of these drugs. Using CRISPR/CAS9 genome library screening, we evaluated Kelch-like ECH-associated protein 1 (KEAP1) as a key regulator of sorafenib's susceptibility in HCC. We also investigated whether KEAP1's knockdown can stabilize nuclear factor (erythroid-derived 2)-like 2 (NRF2) protein levels that led to sorafenib's resistance, including an NRF2 inhibitor that can synergize with sorafenib to abolish HCC's growth in vitro and in vivo. Furthermore, we clarified that fibroblast growth factor 21 (FGF21) is an important downstream regulator of NRF2 in HCC. Intriguingly, we observed that FGF21 bound to NRF2 through the C-terminus of FGF21, thereby stabilizing NRF2 by reducing its ubiquitination and generating a positive feedback loop in sorafenib-resistant HCC. These findings, therefore, propose that targeting FGF21 is a promising strategy to combat HCC sorafenib's resistance.

Targeting mutant p53 for cancer therapy: direct and indirect strategies.

TP53 is a critical tumor-suppressor gene that is mutated in more than half of all human cancers. Mutations in TP53 not only impair its antitumor activity, but also confer mutant p53 protein oncogenic properties. The p53-targeted therapy approach began with the identification of compounds capable of restoring/reactivating wild-type p53 functions or eliminating mutant p53. Treatments that directly target mutant p53 are extremely structure and drug-species-dependent. Due to the mutation of wild-type p53, multiple survival pathways that are normally maintained by wild-type p53 are disrupted, necessitating the activation of compensatory genes or pathways to promote cancer cell survival. Additionally, because the oncogenic functions of mutant p53 contribute to cancer proliferation and metastasis, targeting the signaling pathways altered by p53 mutation appears to be an attractive strategy. Synthetic lethality implies that while disruption of either gene alone is permissible among two genes with synthetic lethal interactions, complete disruption of both genes results in cell death. Thus, rather than directly targeting p53, exploiting mutant p53 synthetic lethal genes may provide additional therapeutic benefits. Additionally, research progress on the functions of noncoding RNAs has made it clear that disrupting noncoding RNA networks has a favorable antitumor effect, supporting the hypothesis that targeting noncoding RNAs may have potential synthetic lethal effects in cancers with p53 mutations. The purpose of this review is to discuss treatments for cancers with mutant p53 that focus on directly targeting mutant p53, restoring wild-type functions, and exploiting synthetic lethal interactions with mutant p53. Additionally, the possibility of noncoding RNAs acting as synthetic lethal targets for mutant p53 will be discussed.

Development of an Aerobic Glycolysis Index for Predicting the Sorafenib Sensitivity and Prognosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a deadly tumor with high heterogeneity. Aerobic glycolysis is a common indicator of tumor growth and plays a key role in tumorigenesis. Heterogeneity in distinct metabolic pathways can be used to stratify HCC into clinically relevant subgroups, but these have not yet been well-established. In this study, we constructed a model called aerobic glycolysis index (AGI) as a marker of aerobic glycolysis using genomic data of hepatocellular carcinoma from The Cancer Genome Atlas (TCGA) project. Our results showed that this parameter inferred enhanced aerobic glycolysis activity in tumor tissues. Furthermore, high AGI is associated with poor tumor differentiation and advanced stages and could predict poor prognosis including reduced overall survival and disease-free survival. More importantly, the AGI could accurately predict tumor sensitivity to Sorafenib therapy. Therefore, the AGI may be a promising biomarker that can accurately stratify patients and improve their treatment efficacy.

TAK1 Is a Novel Target in Hepatocellular Carcinoma and Contributes to Sorafenib Resistance.

BACKGROUND & AIMS: Identifying novel and actionable targets in hepatocellular carcinoma (HCC) remains an unmet medical need. TAK1 was originally identified as a transforming growth factor-ß-activated kinase and was further proved to phosphorylate and activate numerous downstream targets and promote cancer progression. However, the role of TAK1 in developed HCC progression and targeted therapy resistance is poorly understood. METHODS: The expression of TAK1 or MTDH in HCC cell lines, tumor tissues, and sorafenib-resistant models was analyzed by in silico analysis, quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry. In vivo and in vitro experiments were introduced to examine the function of TAK1 or MTDH in HCC and sorafenib resistance using small interfering RNA and pharmacologic inhibitors in combination with or without sorafenib. Co-immunoprecipitation and RNA immunoprecipitation were carried out to determine the binding between TAK1 and FBXW2 or between MTDH and FBXW2 mRNA. Protein half-life and in vitro ubiquitination experiment was performed to validate whether FBXW2 regulates TAK1 degradation. RESULTS: Our findings unraveled the clinical significance of TAK1 in promoting HCC and sorafenib resistance. We identified a novel E3 ubiquitin ligase, FBXW2, targeting TAK1 for K48-linked polyubiquitylation and subsequent degradation. We also found that MTDH contributes to TAK1 up-regulation in HCC and sorafenib resistance through binding to FBXW2 mRNA and accelerates its degradation. Moreover, combination of TAK1 inhibitor and sorafenib suppressed the growth of sorafenib-resistant HCCLM3 xenograft in mouse models. CONCLUSIONS: These results revealed novel mechanism underlying TAK1 protein degradation and highlighted the therapeutic value of targeting TAK1 in suppressing HCC and overcoming sorafenib resistance.

UBQLN1 mediates sorafenib resistance through regulating mitochondrial biogenesis and ROS homeostasis by targeting PGC1ß in hepatocellular carcinoma.

The treatment for hepatocellular carcinoma (HCC) is promising in recent years, but still facing critical challenges. The first targeted therapy, sorafenib, prolonged the overall survival by months. However, resistance often occurs, largely limits its efficacy. Sorafenib was found to target the electron transport chain complexes, which results in the generation of reactive oxygen species (ROS). To maintain sorafenib resistance and further facilitate tumor progression, cancer cells develop strategies to overcome excessive ROS production and obtain resistance to oxidative stress-induced cell death. In the present study, we investigated the roles of ROS in sorafenib resistance, and found suppressed ROS levels and reductive redox states in sorafenib-resistant HCC cells. Mitochondria in sorafenib-resistant cells maintained greater functional and morphological integrity under the treatment of sorafenib. However, cellular oxygen consumption rate and mitochondria DNA content analyses revealed fewer numbers of mitochondria in sorafenib-resistant cells. Further investigation attributed this finding to decreased mitochondrial biogenesis, likely caused by the accelerated degradation of peroxisome proliferator-activated receptor γ coactivator 1ß (PGC1ß). Mechanistic dissection showed that upregulated UBQLN1 induced PGC1ß degradation in a ubiquitination-independent manner to attenuate mitochondrial biogenesis and ROS production in sorafenib-resistant cells under sorafenib treatment. Furthermore, clinical investigations further indicated that the patients with higher UBQLN1 levels experienced worse recurrence-free survival. In conclusion, we propose a novel mechanism involving mitochondrial biogenesis and ROS homeostasis in sorafenib resistance, which may offer new therapeutic targets and strategies for HCC patients.

miR-486-3p mediates hepatocellular carcinoma sorafenib resistance by targeting FGFR4 and EGFR.

HCC is a common malignancy worldwide and surgery or reginal treatments are deemed insufficient for advanced-stage disease. Sorafenib is an inhibitor of many kinases and was shown to benefit advanced HCC patients. However, resistance emerges soon after initial treatment, limiting the clinical benefit of sorafenib, and the mechanisms still remain elusive. Thus, this study aims to investigate the mechanisms of sorafenib resistance and to provide possible targets for combination therapies. Through miRNA sequencing, we found that miR-486-3p was downregulated in sorafenib resistant HCC cell lines. Cell viability experiments showed increased miR-486-3p expression could induce cell apoptosis while miR-486-3p knockdown by CRISPR-CAS9 technique could reduce cell apoptosis in sorafenib treatment. Clinical data also indicated that miR-486-3p level was downregulated in tumor tissue compared with adjacent normal tissue in HCC patients. Mechanism dissections showed that FGFR4 and EGFR were the targets of miR-486-3p, which was verified by luciferase reporter assay. Importantly, FGFR4 or EGFR selective inhibitor could enhance sorafenib efficacy in the resistant cells. Moreover, in vivo sorafenib resistant model identified that over-expressing miR-486-3p by lentivirus injection could overcome sorafenib resistance by significantly suppressing tumor growth in combination with the treatment of sorafenib. In conclusion, we found miR-486-3p was an important mediator regulating sorafenib resistance by targeting FGFR4 and EGFR, thus offering a potential target for HCC treatment.

A Comparison Between the Prognosis of Simultaneous and Salvage Radical Resection in Incidental Gallbladder Cancer.

PURPOSE: Incidental gallbladder cancer (IGBC) is defined as gallbladder cancer (GBC) that is accidentally discovered during cholecystectomy to treat benign lesions. We aimed to compare the prognosis of IGBC patients who underwent simultaneous radical resection (SIR) vs salvage radical resection (SAR). PATIENTS AND METHODS: We retrospectively reviewed data for IGBC patients admitted to Sir Run Run Shaw Hospital from January 2000 to May 2016. Survival analysis was performed using Kaplan-Meier (univariate) and COX regression (multivariate) analyses. RESULTS: Eighty-four patients with IGBC underwent radical resection; 43/84 underwent SIR, and 41/84 underwent SAR. Compared with SIR, the SAR group was more likely to receive comprehensive preoperative radiographic evaluation, port-site excision, and have more lymph nodes excised (all P < 0.05). Kaplan-Meier analysis indicated that the prognosis in the SAR group was better than that in SIR (overall survival: P = 0.050, recurrence-free survival: P = 0.028). Regression analysis indicated that the type of radical resection (SIR/SAR) was not an independent prognostic factor (overall survival: P = 0.737, recurrence-free survival: P = 0.957). CONCLUSION: Patients undergoing SAR had non-inferior survival compared with SIR. It is possible that patients in SAR underwent preoperative radiographical evaluations more comprehensively and the surgical operations were more well performed.

Can laparoscopic liver resection provide a favorable option for patients with large or multiple intrahepatic cholangiocarcinomas?

BACKGROUND: The role of laparoscopic liver resection (LLR) for large or multiple intrahepatic cholangiocarcinomas (ICCs) remains equivocal. The main concerns are potential risks of inadequate resection margin, tumor rupture, uncontrollable bleeding, tumor seeding, and inadequate lymph node sampling. In this study, we aimed to determine the safety, feasibility, and oncological efficacy of LLR for large (≥5 cm) or multiple (≥2) ICCs. METHODS: Among 50 patients receiving liver resection for ICC between May 2004 and January 2016, 12 patients who had undergone LLR for large or multiple ICCs (Group A, n = 12) were compared with 18 patients who had undergone LLR for small solitary ICCs (Group B, n = 18), as well were compared with 20 patients who had undergone open liver resection for large or multiple ICCs (Group C, n = 20). Perioperative and long-term outcomes were analyzed. RESULTS: Compared with Group B, Group A had fewer patients with T1 tumors (58.3 vs. 100%; P = 0.006) and a longer hospital stay (14 vs. 9 days; P = 0.039); operating time, blood loss, surgical margin, cases receiving lymph node dissection, conversion rates, and morbidity were comparable. There were no life-threatening complications and no mortality. No tumor rupture or dissemination occurred, nor did port-site recurrence follow surgery. After a median follow-up of 22 months, no difference was noted in 3-year overall survival (56.3 vs. 59.5%; P > 0.05) and recurrence-free survival (43.8 vs. 50%; P > 0.05) between the two groups. Similarly, perioperative and long-term outcomes were comparable between Group A and Group C. CONCLUSION: LLR for large or multiple ICCs is technically safe, feasible, and oncologically effective in select patients. It provides a favorable option for patients seeking curative treatment. The minimally invasive nature will benefit these patients without compromising the oncological efficacy. Future larger-scale studies and well-designed randomized trials are warranted to evaluate this issue.

Can retrohepatic tunnel be quickly and easily established for laparoscopic liver hanging maneuver by Goldfinger dissector in laparoscopic right hepatectomy?

OBJECTIVE: The liver hanging maneuver (LHM) is rarely applied in laparoscopic right hepatectomy (LRH) because of the difficulty encountered in retrohepatic tunnel (RT) dissection and tape positioning. Thus far no report has detailed how to quickly and easily establish RT for laparoscopic LHM in LRH, nor has employment of the Goldfinger dissector to create a total RT been reported. This study's aim was to evaluate the safety and feasibility of establishing RT for laparoscopic LHM using the Goldfinger dissector in LRH. METHODS: Between March 2015 and July 2015, five consecutive patients underwent LRH via the caudal approach with laparoscopic LHM. A five-step strategy using the Goldfinger dissector to establish RT for laparoscopic LHM was adopted. Perioperative data were analyzed. RESULTS: The median age of patients was 58 (range, 51-65) years. Surgery was performed for one intrahepatic lithiasis and four hepatocellular carcinomas with a median size of 90 (40-150) mm. The median operative time was 320 (282-358) min with a median blood loss of 200 (200-600) ml. Laparoscopic LHM was achieved in a median of 31 (21-62) min, and the median postoperative hospital stay was 14 (9-16) d. No transfusion or conversion was required, and no severe liver-related morbidity or death was observed. CONCLUSIONS: The Goldfinger dissector is a useful instrument for the establishment of RT. A five-step strategy using the Goldfinger dissector can quickly and easily facilitate an RT for a laparoscopic LHM in LRH.

Laparoscopic Right Hepatectomy by the Caudal Approach Versus Conventional Approach: A Comparative Study.

BACKGROUND: Laparoscopic right hepatectomy (LRH) is increasingly performed for the treatment of many liver diseases. However, it remains a challenging procedure and is limited to highly specialized centers. Increasing the safety and efficacy of LRH is crucial. This study evaluated the safety and feasibility of the novel caudal approach (CDA) in LRH and in comparison with the conventional approach (CA). METHODS: Of a total of 40 patients who underwent LRH between June 2007 and July 2015 at our center, 10 cases underwent the CDA, while 30 underwent the CA. Operative and postoperative outcomes were analyzed. RESULTS: Clinical data and patient characteristics were comparable between the two groups. Only 1 patient required a laparoscopic-assisted procedure in the CDA group, while 14 patients were converted to laparotomy (n = 10) or laparoscopic-assisted procedures (n = 4) in the CA group, although the difference did not reach statistical significance (P = .060). However, the difference in conversion to laparotomy between the two groups was significant (P = .043). In addition, when considering 23 patients with malignancies, the median surgical margin was significantly greater in the CDA group (n = 6) (20 mm versus 10 mm; P = .023) than in the CA group (n = 17). Other operative and postoperative outcomes were similar between the two groups. CONCLUSIONS: The CDA achieves safety and feasibility similar to that of the CA in LRH and requires relatively less conversion to laparotomy. In selected patients, the CDA offers an alternative option to the CA for LRH in experienced hands. Further studies with larger samples are warranted to evaluate the CDA.

Enhanced Recovery Program Versus Traditional Care in Laparoscopic Hepatectomy.

Enhanced recovery after surgery (ERAS) has shown effectiveness in terms of reducing the hospital stay and cost associated with open liver resection. However, the benefit of ERAS in patients undergoing laparoscopic liver resection is still unclear, and clinical studies on this topic are limited.The ERAS program for laparoscopic liver resection was used in a group of 80 patients (ERAS group). The results were compared with those in a control group of 107 patients. All patients underwent laparoscopic liver resection. The primary endpoints were the postoperative hospital stay, defined as the number of days from surgery to discharge, and the hospitalization expense. The secondary endpoints were resumption of oral intake, readmissions, and complications.The median postoperative hospital stay was 6.2 ±â€Š2.6 days in the ERAS group, which was significantly shorter than that in the control group (9.9 ±â€Š5.9 d; P < 0.001). The hospitalization cost was $6871 ±â€Š2571 in the ERAS group and $7948 ±â€Š3630 in the control group (P = 0.020). The morbidity rate was 22.5% (18 of 80 patients) in the ERAS group and 43.9% (47 of 107 patients) in the control group (P = 0.002). There were no significant differences the in rate of readmission between the 2 groups.Enhanced recovery after surgery for laparoscopic liver resection is safe and effective. Patients in the ERPS group had a shorter hospital stay, fewer complications, and lower hospital costs.

Is Laparoscopic Hepatectomy a Safe, Feasible Procedure in Patients with a Previous Upper Abdominal Surgery?

BACKGROUND: Laparoscopic liver resection has become an accepted treatment for liver tumors or intrahepatic bile duct stones, but its application in patients with previous upper abdominal surgery is controversial. The aim of this study was to evaluate the feasibility and safety of laparoscopic hepatectomy in these patients. METHODS: Three hundred and thirty-six patients who underwent laparoscopic hepatectomy at our hospital from March 2012 to June 2015 were enrolled in the retrospective study. They were divided into two groups: Those with previous upper abdominal surgery (PS group, n = 42) and a control group with no previous upper abdominal surgery (NS group, n = 294). Short-term outcomes including operating time, blood loss, hospital stay, morbidity, and mortality were compared among the groups. RESULTS: There was no significant difference in median operative duration between the PS group and the NS group (180 min vs. 160 min, P = 0.869). Median intraoperative blood loss was same between the PS group and the control group (200 ml vs. 200 ml, P = 0.907). The overall complication rate was significantly lower in the NS group than in the PS group (17.0% vs. 31.0%, P = 0.030). Mortality and other short-term outcomes did not differ significantly between groups. CONCLUSIONS: Our study showed no significant difference between the PS group and NS group in term of short-term outcomes. Laparoscopic hepatectomy is a feasible and safe procedure for patients with previous upper abdominal surgery.

Laparoscopic hepatectomy by curettage and aspiration: a report of 855 cases.

BACKGROUND: In 1998, the technique of laparoscopic hepatectomy by curettage and aspiration was developed and a special instrument, laparoscopic multifunctional operative dissector (LPMOD), was designed for this procedure. In the past 17 years, this procedure was developed gradually and had become the routine procedure for laparoscopic hepatectomy in local area. This paper is to report results of 17-year practice of this procedure. METHODS: Patients who underwent laparoscopic hepatectomy from August 1998 to March 2015 were reviewed. Hepatectomies were performed using the technique of laparoscopic hepatectomy by curettage and aspiration. By using the LPMOD, liver parenchyma was crashed and aspirated immediately and the intrahepatic ducts and small vessels were preserved and were safely dissected for ligation. Laparoscopic selective hepatic flow occlusion was performed routinely for hemi-hepatectomies to control intraoperative blood loss. RESULTS: A total of 855 cases underwent laparoscopic hepatectomy by curettage and aspiration. No perioperative death, 105 patients were converted to open operation, and 84 of them were converted before liver transection without any emergency. Postoperative bleeding occurred in three patients (0.4 %), and bile leakage occurred in seven patients (0.8 %). CONCLUSION: Laparoscopic hepatectomy by curettage and aspiration is a safe procedure for liver resection with acceptable morbidity and mortality.

[Application of anterior-inferior approach through retrohepatic tunnel for dissecting short hepatic veins in laparoscopic right hemihepatectomy].

OBJECTIVE: To explore the safety and feasibility of laparoscopic right hemihepatectomy via an anterior-inferior approach through retrohepatic tunnel in the dissection of short hepatic veins (SHVs). METHODS: After partial freeing of right liver, anterior peritoneum of inferior cava vena (ICV) was opened. Retrohepatic space was dissected via an anterior-inferior approach to establish the posterior tunnel partially. Then the first branch of right side SHVs could be freed and ligated after its exposure through the right part of retrohepatic tunnel. The above procedure was repeated until the right side SHVs or the third hepatic portal became partially or completely blocked. If right side SHVs were completely freed and ligament of right liver fully isolated, right hepatic vein could be exposed and ligated and selective blockage of the second hepatic portal blood flow accomplished. This technique was applied in 7 cases of laparoscopic right hemihepatectomy through curettage transaction and aspiration with laparoscopic Peng's multifunctional operative dissector (LPMOD). RESULTS: Six patients were treated successfully. In one case of right hepatic hemangioma, small margin auxiliary hematischesis was attempted because of troublesome hemostasis of middle hepatic vein branch. All of them underwent partial dissection of right side of SHVs. Two cases had complete dissection in which right hepatic vein was freed and ligated, the second hepatic porta blood flow controlled and right hemihepatectomy anatomically achieved. Operative duration was 300-540 min [mean, 399.1 ± 74.7]. The time of dissecting hepatic porta was 30-75 min [mean, 50.7 ± 16.2]. The time of dissecting SHVs was 35-95 min [mean, 57.1 ± 22.1]. The time of liver transection was 60-160 min [mean, 115.9 ± 32.3]. Operative blood loss had a volume at 600-3000 ml [mean, 1485.7 ± 809.2]. The postoperative hospital stay was 10-18 days [mean, 12.4 ± 2.6]. The postoperative time for ambulation, diet and flatus was 2-4, 1-4 and 2-4 days respectively. No severe postoperative complications occurred. CONCLUSION: During laparoscopic right hemihepatectomy, dissecting SHVs is both safe and feasible through a retrohepatic tunnel via an anterior-inferior approach.

[Application of bio-mesh-reinforced pancreatico-gastrostomy after pancreaticoduodenectomy].

OBJECTIVE: To evaluate the clinical efficacy of bio-mesh-reinforced pancreaticogastrostomy. METHODS: A total of 23 patients undergoing bio-mesh-reinforced pancreaticogastrostomy from May 2011 to January 2013 were retrospectively analyzed. Their demographic data, operative parameters and post-operative outcomes were recorded. The severity of pancreatic leak was determined according to the criteria of International Study Group on Pancreatic Fistula (ISGPF). RESULTS: The mean anastomotic time was 24 (20-35) minutes. Intra-operative leak tests showed all pancreatic anastomoses were watertight. Six patients (26.1%) had pancreatic leakage of grade A. One patient (4.3%) had pancreatic leakage of grade B. No patient developed postoperative pancreatic leakage of class C. One case of abdominal infection was reported. No severe complications such as hemorrhage, bile leakage or gastrojejunostomy leakage were observed. All patients recovered well within Month 1 post-discharge. CONCLUSION: This novel technique may be a simple and feasible strategy for all types of pancreatic remnants.

Reexpression of ARHI inhibits tumor growth and angiogenesis and impairs the mTOR/VEGF pathway in hepatocellular carcinoma.

The Ras-related tumor suppressor gene aplasia Ras homolog member I (ARHI) is frequently downregulated in many types of cancer, including hepatocellular carcinoma (HCC). In this study, we sought to explore the therapeutic implications of ARHI reconstitution in the treatment of HCC. We generated stable cell lines overexpressing ARHI in Hep3B and SK-Hep1 cells, both of which lack endogenous ARHI. The effects of ARHI reexpression on tumor growth and angiogenesis were assessed. Given the key role of mammalian target of rapamycin (mTOR) signaling in HCC progression, we also tested whether ARHI overexpression affected the mTOR pathway. Forced expression of ARHI resulted in a significant inhibition of the proliferation of both Hep3B and SK-Hep1 cells compared to control cells (P<0.01). Cell cycle analysis revealed a G0-G1 arrest induced by ARHI reexpression. Moreover, ARHI reexpression significantly retarded Hep3B xenograft growth in vivo, and caused a marked reduction in tumor angiogenesis assessed by CD31-stained microvessel count. Western blot analysis of the xenografts showed that ARHI overexpression substantially reduced the phosphorylation of two mTOR substrates, S6K1 and 4E-BP1, indicative of an inactivation of the mTOR pathway. Accompanying with the mTOR inactivation, the angiogenic factors, hypoxia-inducible factor 1 alpha and vascular endothelial growth factor, were significantly downregulated. These data highlighted an important role for ARHI in controlling HCC growth and angiogenesis, therefore offering a possible therapeutic strategy against this malignancy.