Indocyanine green real-time-guided laparoscopic duodenum-preserving pancreatic head resection.

Duodenum-preserving pancreatic head resection (DPPHR) is very complicated due to its difficulty to find the lower common bile duct (CBD), and to preserve the blood supply of the duodenum and CBD. Recently, indocyanine green (ICG) has been widely applied for navigation during biliary system and liver surgery. However, the application of ICG-guided laparoscopic DPPHR has not been established. Herein, we report an intraoperative angiography technique using ICG fluorescence imaging to visualise blood flow, tissue perfusion, CBD navigation and bile leakage assessment.

Study of ultrasound-guided percutaneous microwave ablation combined with portal vein embolization for rapid future liver remnant increase of planned hepatectomy.

Purpose: To evaluate the efficacy of ultrasound-guided percutaneous microwave ablation (PMA) combined with portal vein embolization (PVE) for planned hepatectomy. Methods: We retrospectively reviewed data of 18 patients with multiple right liver tumors or hilar tumor of liver invades the surrounding tissue and insufficient future liver remnant (FLR) for hepatectomy from July 2015 to March 2017. Ultrasound-guided PMA was performed by using PMCT cold circulation microwave treatment apparatus. PVE was performed after PMA. The increase of FLR was evaluated by computed tomography (CT) 6-22 days after PVE. The proportion of FLR, increase in the amplitude of FLR, procedure-related complications, perioperative morbidity and mortality, and overall survival (OS) rates, the median survival time were analyzed. Results: The median volume of FLR before PMA and PVE was 369.7 ml (range: 239.4-493.1 ml). After a median waiting period of 11.5 days (range: 6-22 days), the median volume of FLR was increased to 523.4 ml (range: 355.4-833.3 ml). The changes in FLR before and after PMA and PVE were statistically significant (p<0.001). No serious perioperative complications or mortality were found. After a median follow-up time of 51.0 months (range: 2-54 months), the 6-month, 1-year, 2-year, 3-year and 4-year survival rates were 88.9%, 72.2%, 44.4%, 33.3%, 22.2%, respectively, and the median survival time was 15.0 ± 7.1 months. Conclusion: PMA combined with PVE increases FLR rapidly, avoids touching malignant tumors, and produces fewer procedure-related complications. It appears safe and efficacious for planned hepatectomy.

linc­ROR facilitates hepatocellular carcinoma resistance to doxorubicin by regulating TWIST1­mediated epithelial­mesenchymal transition.

Long non­coding RNAs are associated with cancer progression. Long intergenic non­protein coding RNA (linc)­regulator of reprogramming (ROR) enhances tumor development in hepatocellular carcinoma (HCC). However, the effect of chemoresistance and its underlying mechanisms in HCC are not completely understood. The present study aimed to identify the effect of ROR on sensitivity to doxorubicin (DOX) in HCC cells. In the present study, Cell Counting Kit­8 and EdU assays were performed to assess cell viability and proliferation, respectively. In addition, E­cadherin and vimentin protein expression levels were assessed via western blotting and immunofluorescence.The results of the present study demonstrated that HCC cells with high linc­ROR expression levels were more resistant to DOX, and linc­ROR knockdown increased HCC cell DOX sensitivity compared with the control group. The results indicated that compared with the NC siRNA group, linc­ROR knockdown notably suppressed epithelial­mesenchymal transition by downregulating twist family bHLH transcription factor 1 (TWIST1) expression. TWIST1 knockdown displayed a similar effect on HCC cell DOX sensitivity to linc­ROR knockdown. Moreover, linc­ROR knockdown­induced HCC cell DOX sensitivity was inhibited by TWIST1 overexpression. The present study provided evidence that linc­ROR promoted HCC resistance to DOX by inducing EMT via interacting with TWIST1. Therefore, linc­ROR might serve as a therapeutic target for reducing DOX resistance in HCC.

Safety and feasibility of laparoscopic versus open liver resection with associated lymphadenectomy for intrahepatic cholangiocarcinoma.

The safety and feasibility of laparoscopic versus open liver resection (LLR vs. OLR) associated lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) are still controversial. The aim of the present study was to compare short and long-term outcomes. We reviewed data on 43 consecutive patients who underwent curative liver resection with associated lymphadenectomy for ICC. The short-term outcomes including postoperative morbidity and mortality, and the long-term outcomes including overall survival (OS) and recurrence-free survival (RFS) were compared. The median survival, 1- and 3-year OS in LLR and OLR groups were 22.5 months, 76.9% and 47.1%, and 12.1 months, 43.1% and 20.0%, respectively. The median survival, 1- and 3-year RFS in LLR and OLR groups were 10.3 months, 27.8% and 0%, and 8.1 months, 24.0% and 4.0%, respectively. The results showed that LLR obviously reduced intraoperative blood loss (median, 375 vs. 500ml, p = 0.016) and postoperative hospital stay (median, 6 vs. 9 days, p = 0.016). Moreover, there was no significant difference in short-term outcomes including postoperative morbidity (including wound infection, bile leakage, liver failure and pneumonia) and mortality within 30 days, and long-term outcomes including OS and RFS between LLR and OLR. (all p > 0.05). Multivariate analysis showed that CA19-9 level, TNM stage, and tumor differentiation were independent risk factors for OS and RFS. LLR for ICC is safety and feasibility compared with OLR. The advantage of LLR was to reduce intraoperative blood loss and postoperative hospital stay.

Microplastic abundance, distribution and composition in the mid-west Pacific Ocean.

Microplastic pollution is widespread across most ocean basins around the world. Microplastics (MPs) are small plastic particles that have a significant impact on the marine environment. Various research on plastic pollution have been conducted in several regions. However, currently, there is limited data on the distribution and concentration of MPs in the mid-west Pacific Ocean. Therefore, this study we investigated the abundance, distribution, characteristics, and compositions of MPs in this region. Sea surface water samples collected from 18 stations showed a microplastic concentration range of 6028-95,335 pieces/km2 and a mean concentration of 34,039 ± 25,101 pieces/km2. Highest microplastic concentrations were observed in the seamount region of western Pacific. We observed a significant positive correlation between microplastic abundance and latitude across the study region. It was observed that microplastic concentrations decreased with increasing offshore distance at sites located on a 154° W transect. Fibres/filaments were the dominant microparticles observed in this study (57.4%), followed by fragments (18.3%). The dominant particle size range was 1-2.5 mm (35.1%), followed by 0.5-1 mm (28.5%), and the dominant particle colour was white (33.8%), followed by transparent (31.0%) and green (24.6%). The most common polymer identified by µ-Raman was polypropylene (39.1%), followed by polymethyl methacrylate (16.2%), polyethylene (14.1%) and polyethylene terephthalate (14.2%). The possible sources and pathways of microplastics in the study area were proposed based on the morphological and compositional characteristics of particles, their spatial distribution patterns, and shipboard current profiling (ADCP). Our study contributes to the further understanding of MPs in remote ocean areas.

Prevalence of microplastic pollution in the Northwestern Pacific Ocean.

People are increasingly aware of ubiquitous microplastic (MP) pollution in the world's ocean due to its far-reaching harmful impacts on marine ecosystem and potential hazards to human health, yet surprisingly comparatively limited studies about the abundance, source, transport, and fate of MPs in the Northwestern Pacific Ocean are available. We conducted the field survey of MPs pollution at the surface of the Northwestern Pacific Ocean between August 25 and September 26, 2017. MPs were collected from 18 sampling stations in the Northwestern Pacific Ocean using a manta trawl net with a mesh size of ∼330 µm and a rectangular net opening of 0.45 × 1 m. The abundance, shape, color, size, chemical composition, and surface morphology were characterized using light microscopy, µ-Raman spectroscopy, and scanning electron microscopy (SEM). The results show surface MPs at concentrations ranging over two orders of magnitude (6.4 × 102 to 4.2 × 104 particles km-2) and a mean abundance of 1.0 × 104 particles km-2. The most concentrated MPs were found at XTJ3-9, which may be associated with the convergence of surface currents collectively affected by the Kuroshio and its extension, adjacent eddies, and flow regimes. Polyethylene accounts for 57.8% of enumerated MPs, followed by polypropylene (36.0%) and nylon (3.4%). Pellets, sheets, lines, and films are major forms which may be linked to the breakdown of larger particles, aging processes, and movement over long distances by prevailing currents. Four possible MPs migration pathways were proposed based on the source-specific distribution, chemical fingerprints, size distribution patterns, and the observed physical oceanographic parameters.

Microplastics in the Northwestern Pacific: Abundance, distribution, and characteristics.

Prevalence of microplastics (MPs) throughout the world's oceans has raised growing concerns due to its detrimental effects on the environment and living organisms. Most recent studies of MPs, however, have focused on the estuaries and coastal regions. There is a lack of study of MPs pollution in the open ocean. In the present study, we conducted field observations to investigate the abundance, spatial distribution, and characteristics (composite, size, color, shape and surface morphology) of MPs at the surface of the Northwestern Pacific Ocean. Samples of MPs were collected at 18 field stations in the Northwestern Pacific Ocean using a surface manta trawl with a mesh size of ~330 µm and width of 1 m from August 25 to September 26, 2017. The MPs were characterized using light microscopy, Micro-Raman spectroscopy, and scanning electron microscopy (SEM). Our field survey results indicate the ubiquity of MPs at all stations with an abundance from 6.4 × 102 items km-2 to 4.2 × 104 items km-2 and an average abundance of 1.0 × 104 items km-2. The Micro-Raman spectroscopic analysis of the MPs samples collected during our field survey indicates that the dominant MPs is polyethylene (57.8%), followed by polypropylene (36.0%) and nylon (3.4%). The individual chemical compositions of MPs from the stations within the latitude range 123-146°E are comparable with each other, with PE being the dominating composition. Similar chemical fingerprints were observed at these field stations, suggesting that the MPs originated from similar sources. In contrast, the major MPs at the field stations adjacent to Japan is polypropylene, which may originate from the nearby land along the coast of Japan. Physical oceanography parameters were also collected at these stations. The spatial distribution of MPs is largely attributed to the combined effects of flow pattern, adjacent ocean circulation eddies, the Kuroshio and Kuroshio Extension system.

FSCN­1 increases doxorubicin resistance in hepatocellular carcinoma through promotion of epithelial-mesenchymal transition.

Resistance to chemotherapy drugs remains a significant problem for the treatment of many types of cancer. Fascin­1 (FSCN­1) is an actin-bundling protein involved in the invasion and metastasis of a variety of tumors. However, its involvement in drug resistance in hepatocellular carcinoma (HCC) remains unclear. The present study aimed to investigate the function of FSCN­1 in HCC resistance to doxorubicin (DOX). FSCN­1 expression was increased in DOX-resistant HCC cell lines (SNU449 and SNU387) compared with DOX-sensitive cell lines (Huh7 and Hep3B). The resistance of HCC cells to DOX was decreased following FSCN­1 knockdown with small interfering RNA. FSCN­1 knockdown also significantly altered the expression of key markers of epithelial-mesenchymal transition (EMT). Notably, vimentin expression was reduced and epithelial­cadherin expression was increased. Furthermore, when EMT was suppressed through knockdown of Twist, an essential pathway of DOX-induced EMT, the viability of HCC cells following treatment with DOX was not affected by FSCN­1 expression. Furthermore, FSCN­1 knockdown eliminated hypoxia-induced doxorubicin resistance and EMT. The results of the present study indicated that FSCN­1 expression increased DOX resistance in HCC cells via the promotion of EMT, and this phenomenon was maintained in a hypoxic environment. FSCN­1 potentially represents a novel target to overcome resistance to DOX in HCC.

Binding pancreaticogastrostomy in laparoscopic central pancreatectomy: a novel technique in laparoscopic pancreatic surgery.

BACKGROUND: Even though more and more cases of laparoscopic central pancreatectomy (LCP) are reported (Machado et al. in Surg Laparosc Endosc Percutan Tech 23(6):486-490, 2013; Hong et al. in World J Surg Oncol 10:223, 2012; Gonzalez et al. in JOP 14(3):273-276, 2013, Zhang et al. in J Laparoendosc Adv Surg Tech A 23(11):912-918, 2013; Sucandy et al. in N Am J Med Sci 2(9):438-441, 2010; Sa Cunha et al. in Surgery 142(3):405-409, 2007), the management for pancreatic stumps remains the most technically challenging part which is the same as in pancreatoduodenectomy (PD), making it the bottleneck for laparoscopic pancreatic surgery. In open surgery, various pancreatic reconstruction techniques designed for either pancreaticojejunostomy (PJ) or pancreaticogastrostomy (PG) have been attempted to reduce the postoperative pancreatic fistula (POPF), including the binding anastomosis, invented by our team, i.e., binding PG (BPG) and binding PJ, which have been proved to be effective to reduce the POPF (Hong et al. 2012; Peng et al. in Ann Surg 245(5):692-698, 2007; Peng et al. in Updates Surg 63(2):69-74, 2011). However, despite of this, few reports are seen addressing such technique for laparoscopic surgery even though laparoscopic pancreatic surgery is more performed. After a previous successful laparoscopic BPG in a case of laparoscopic CP (LCP; Hong et al. 2012) and more than 50 cases of open PD and CP (Peng et al. 2011), we further performed laparoscopic BPG in 10 consecutive cases of LCP with satisfactory outcomes. OBJECTIVE: To explore the feasibility and efficacy of LCP with BPG. METHODS: Between October 2011 and July 2014, LCP with laparoscopic BPG was performed in ten consecutive patients with lesions of benign or low malignancy at the pancreatic neck. Operative and pathological data, complications, hospital stay and details on the surgical techniques were introduced. RESULTS: The operations were successfully performed in all the ten cases, with no conversions. The tumor size ranged from 2.0-3.0 to 2.5-3.0 cm, average (2.50 ± 0.35) to (2.66 ± 0.35) cm, and the diameter of pancreatic duct was (1.6-2.1) mm, average (1.71 ± 0.17) mm. Operation time was 170-250 (198.50 ± 25.82) min, and blood loss was 20-300 (125 ± 107.31) mL. Three cases had grade A pancreatic fistula (PF), and one case had delayed gastric emptying, which were all managed with conservative treatment. Upper GI bleeding occurred in one case which was cured with second operation, time for the recovery of bowl movement was 3-5 (4.2 ± 0.8) days, the time for semifluid dieting was 6-10 (8.2 ± 1.5) days, and the hospital stay was 8-20 (12.8 ± 4.63) days. The postoperative fast blood sugar was (6.3 ± 1.6) mmol/L with the normal diet, which was not significantly different from the preoperative data (5.3 ± 0.5) mmol/L (P > 0.05). The postoperative pathology was as follows: five cases of cystic serous adenoma, one case of intraductal papillary mucinous neoplasm, two cases of neuroendocrine tumor, and two cases of solid pseudopapillary tumor of pancreas. All the patients were followed up for 7-40 months, no recurrence happened, and no new incidence of diabetes or insufficiency of pancreatic exocrine function occurred. CONCLUSIONS: LCP with BPG is feasible and safe; the advantages lie in its minimal invasiveness, the efficacy for avoiding PF, and the preservation of the pancreatic endocrine and exocrine function insufficiency, making it an ideal procedure for the benign or low-malignant lesions at the pancreatic neck.

Management of hepatocellular carcinoma rupture in the caudate lobe.

AIM: To demonstrate that caudate lobectomy is a valid treatment in cases of hepatocellular carcinoma (HCC) rupture in the caudate lobe based on our experience with the largest case series reported to date. METHODS: A retrospective study of eight patients presenting with spontaneous rupture and hemorrhage of HCC in the caudate lobe was conducted. Two patients underwent ineffective transarterial embolization preoperatively. Caudate lobectomy was performed in all eight patients. Bilateral approach was taken in seven cases for isolated complete caudate lobectomy. Left-sided approach was employed in one case for isolated partial caudate lobectomy. Transarterial chemoembolization was performed postoperatively in all patients. RESULTS: Caudate lobectomy was successfully completed in all eight cases. The median time delay from the diagnosis to operation was 5 d (range: 0.25-9). Median operating time was 200 min (range: 120-310) with a median blood loss of 900 mL (range: 300-1500). Five patient remained in long-term follow-up, with one patient becoming lost to follow-up at 3 years and two patients currently alive at 7 and 19 mo. One patient required reoperation due to recurrence. Gamma knife intervention was performed for brain metastasis in another case. Two patients survived for 10 and 84 mo postoperatively, ultimately succumbing to multiple organ metastases. CONCLUSION: Caudate lobectomy is the salvage choice for HCC rupture in the caudate lobe. Local anatomy and physiologic features of the disease render caudate lobectomy a technically difficult operation. Postponement of surgical intervention is thus recommended while the rupture remains hemodynamically stable until an experienced surgeon becomes available. Prognosis is confounded by numerous factors, but long-term survival can be expected in the majority of cases.

Comparison of two laparoscopic splenectomy plus pericardial devascularization techniques for management of portal hypertension and hypersplenism.

OBJECTIVE: Our research was conducted to analyze the outcomes of two laparoscopic splenectomy plus pericardial devascularization (LSPD) techniques in the management of portal hypertension (PTH) and hypersplenism. METHODS: Between May 2012 and May 2013, 41 patients with PTH and hypersplenism undergoing LSPD were retrospectively analyzed. Of them, 29 patients received LSPD by LigaSure Vessel Sealing System (LVSS) and Endo-GIA universal endoscopic vascular linear staplers (Endo-GIA) (EG Group) and 12 patients received LSPD by LVSS and Hem-o-Lock (HL Group). Operating time, intraoperative blood loss, postoperative course, and hospitalization costs were compared between the two LSPD combination techniques. RESULTS: There were no significant differences in preoperative patient characteristics of the two groups. Significantly less operating time, intraoperative blood loss, and postoperative complications were observed in EG Group. The incidence of portal vein thrombosis was lower in the EG Group (3.4 vs. 8.3%), as well as the incidence of pancreatic fistula (0 vs. 8.3%). Upper gastrointestinal hemorrhage was not observed in either group. Uncontrolled bleeding warranted conversion to open surgery in one case in EG Group (conversion rate 3.4%) and in two cases in HL Group (conversion rate 16.7%). Two patients (16.7%) in HL Group underwent successful emergency exploratory laparotomy due to uncontrolled intraabdominal bleeding postoperatively. No re-operation was needed in EG Group. Two patients experienced liver failure after surgery in each group. Of those, three patients were managed successfully and one patient refused further therapy. While the overall complication rate was significantly lower in EG Group (17.2 vs. 58.3%, P < 0.05), overall hospitalization costs remained significantly higher for EG Group. CONCLUSION: The results suggest that the modified Endo-GIA and LVSS technique is a safe and effective combination approach to LSPD with shorter operative time, less intraoperative blood loss, lower conversion rate to laparotomy, shorter hospital stay, better recovery, and lower postoperative complication rate compared with the Hem-o-Lock and LVSS approach. Higher hospitalization expenses associated with the Endo-GIA and LVSS approach.

Sirtuin 1 facilitates chemoresistance of pancreatic cancer cells by regulating adaptive response to chemotherapy-induced stress.

Chemotherapy drugs themselves may act as stressors to induce adaptive responses to promote the chemoresistance of cancer cells. Our previous research showed that sirtuin 1 (SIRT1) was overexpressed in pancreatic cancer patients and deregulation of SIRT1 with RNAi could enhance chemosensitivity. Thus, we hypothesized that SIRT1 might facilitate chemoresistance in pancreatic cancer cells through regulating the adaptive response to chemotherapy-induced stress. In the present study, SIRT1 in PANC-1, BXPC-3, and ASPC-1 cells was upregulated after treatment with gemcitabine. Moreover, the decrease in SIRT1 activity with special inhibitor EX527 had a synergic effect on chemotherapy with gemcitabine in PANC-1 and ASPC-1 cell lines, which significantly promoted apoptosis, senescence, and G0 /G1 cycle arrest. Western blot results also showed that SIRT1, acetylated-p53, FOXO3a, and p21 were upregulated after combined treatment, whereas no obvious change was evident in total p53 protein. To further confirm the role of SIRT1 in clinical chemotherapy, SIRT1 was detected in eight pancreatic cancer tissues acquired by endoscopy ultrasonography guided fine needle aspiration biopsy before and after chemotherapy. Compared to before chemotherapy, SIRT1 was significantly increased after treatment with gemcitabine in six cases. Thus, our results indicated a special role for SIRT1 in the regulation of adaptive response to chemotherapy-induced stress, which is involved in chemoresistance. Moreover, it indicates that blocking SIRT1 activity with targeting drugs might be a novel strategy to reverse the chemoresistance of pancreatic cancer.

Experience in primary hepatic neuroendocrine tumor.

BACKGROUND/AIMS: We aimed to analyze the clinical characteristics, pathologic features, treatment approaches, and prognostic factors of primary hepatic neuroendocrine tumor. MATERIALS AND METHODS: We retrospectively analyzed the clinical characteristics, pathologic features, treatment approaches, and prognostic factors of 9 patients with primary hepatic neuroendocrine tumor treated in our hospital from January 2003 to January 2010. RESULTS: The clinical manifestations were nonspecific and variable. The most common clinical manifestation was distention or right upper quadrant pain. Radiological findings are not specific and cannot distinguish primary hepatic neuroendocrine tumor from hepatocellular carcinoma. Diagnosis of primary hepatic neuroendocrine tumor was confirmed immunohistochemically and by the absence of extrahepatic primary sites. No extrahepatic primary lesions were found by ultrasonography, computed tomography, magnetic resonance imaging or positron emission tomography scan either preoperatively or during the follow-up period in our research. Immunohistologically, synaptophysin, chromogranin A and CD56 should be used as markers to precisely diagnose primary hepatic neuroendocrine tumor. The outcome of primary hepatic neuroendocrine tumor is mostly related to its resectability. Total resection of the neoplasm is most commonly proposed. A multimodality of treatments, including chemotherapy, transarterial chemoembolization and radiofrequency ablation, should be used preor postoperatively to improve the survival. CONCLUSIONS: Primary hepatic neuroendocrine tumor is a rare entity, and its diagnosis is difficult. Preoperative fine needle biopsy is strongly recommended, and primary surgery integrated with chemotherapy, transarterial chemoembolization or radiotherapy is considered to be an effective modality for primary hepatic neuroendocrine tumor.

Pro-apoptotic and anti-proliferative effects of mitofusin-2 via Bax signaling in hepatocellular carcinoma cells.

Mitochondrial GTPase mitofusin-2 (Mfn2) is a novel gene that remarkably suppresses the injury-mediated proliferation of vascular smooth muscle cells (VSMCs) and has a potential apoptotic effect via the mitochondrial apoptotic pathway. Hepatocellular carcinoma (HCC) tissues and matched normal tissues were examined for mfn2 expression. HCC cells were infected with adenovirus carrying Mfn2 (Ad-mfn2) or green fluorescent protein (Ad-GFP), used as a control. Short hairpin RNA (shRNA) was formed by shR-mfn2 and shR-Bax to repress mfn2 and Bax transcription, respectively. The effects of mfn2 on cell cycle distribution and apoptosis were measured by flow cytometric analysis. Significant downregulation of mfn2 was observed in HCC tissues compared with nearby normal tissues. Overexpression of mfn2 inhibited HCC cell proliferation and induced apoptosis by increasing the level of active caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage. Overexpression of mfn2 also induced cytochrome c release to the cytoplasm by enhancing Bax translocation from the cytoplasm to the mitochondrial membrane. Upregulation of mfn2 promoted apoptosis of HCC cells, and this was dramatically suppressed by shR-Bax. Our results show that the mfn2 gene is a potential tumor suppressor target that may significantly promote apoptosis via Bax and may inhibit proliferation in HCC cells. This gene may be an important therapeutic target for the treatment of tumors or hyperproliferative diseases.

HSG provides antitumor efficacy on hepatocellular carcinoma both in vitro and in vivo.

Hyperplasia suppressor gene (HSG) is a novel gene that markedly suppresses the mitogenetic stimuli or injury mediated by vascular smooth muscle cell proliferation. Herein we provide experimental evidence to show that HSG can also play a key role in tumor proliferation. Down-regulation of HSG protein in hepatocellular carcinoma tissues compared to adjacent tissues. Overexpression of HSG suppressed the growth of liver cancer cell lines, resulted in cell cycle arrest in the G0/G1 phase, increased expression of the cyclin dependent kinase inhibitors (CKIs), and reduced expression of proliferating cell nuclear antigen (PCNA). It also showed that adenovirus-mediated HSG overexpression induced apoptosis. Up-regulation of HSG by adenovirus also significantly suppressed the growth of subcutaneous tumors in nude mice both ex vivo and in vivo. Collectively, our data suggest that HSG is a potential therapy for tumors and possibly other proliferative diseases as well and it has antitumor efficacy on hepatocellular carcinoma by using adenovirus vectors, which may be a new therapeutic target for liver cancer prevention.