A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct.

Intraductal papillary neoplasm of the bile duct (IPNB) is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas. These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010. In 2018, Japanese and Korean pathologists reached a consensus, classifying IPNBs into type l and type 2 IPNBs. IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis. From a molecular genetic perspective, IPNBs exhibit early genetic variations, and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs. The histological subtypes of IPNBs include gastric, intestinal, pancreaticobiliary, or oncocytic subtypes, but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin. Due to the rarity of these lesions and the absence of specific clinical and laboratory features, imaging is crucial for the preoperative diagnosis of IPNB, with local bile duct dilation and growth along the bile ducts being the main imaging features. Surgical resection remains the optimal treatment for IPNBs, but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

Comparing triple scope-combined bile duct exploration lithotripsy with laparoscopic hepatectomy for hepatolithiasis (with video).

BACKGROUND: To compare the efficacy of Three-scope combined (laparoscopic, rigid choledochoscopy and electronic choledochoscopy, TS) with laparoscopic hepatectomy (LH) for patients with hepatolithiasis (HL). METHODS: Between January 2019 and January 2020, 118 consecutive patients with HL treated with TS (TS group, n = 57) or LH (LH group, n = 61) were analyzed in this study. Perioperative and long-term outcomes, including operative time, intraoperative blood loss, blood transfusion, postoperative bowel function recovery time, postoperative hospital stay, complication rate, stone removal rate, and stone recurrence rate, were compared and analyzed between the two groups. RESULTS: Compared with the LH group, the TS group had significantly lower intraoperative blood loss and transfusions, significantly shorter operative time and hospital stay, and fewer complications (P < 0.05 for all). There was no significant difference in the final stone removal rate, stone recurrence rate and postoperative bowel function recovery time (P > 0.05 for all). CONCLUSION: TS is a safe and effective treatment for HL and is superior to LH in terms of overall treatment outcome and complications.

Comparative analysis of postoperative curative effect of liver wedge resection and liver IVb + V segment resection in patients with T2b gallbladder cancer.

Objective: To compare the therapeutic effects of wedge resection and liver segment IVb + V resection on patients with T2b gallbladder cancer. Methods: The clinical and pathological data of 40 patients with gallbladder cancer admitted to the Second Affiliated Hospital of Nanchang University from January 2017 to November 2019 were retrospectively analyzed, and they were divided into two groups according to different surgical methods. The control group underwent liver wedge resection, while the experimental group underwent liver segment IVb + V resection. Preoperative age, bilirubin index, tumor markers, postoperative complications and survival were compared between the two groups. Log-rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis. Kaplan-Meier survival curves were drawn. Results: Univariate analysis showed that tumor markers and degree of differentiation were the risk factors for the prognosis of patients with gallbladder carcinoma after radical cholecystectomy (P < 0.05). Multivariate analysis showed that the elevation of CA125 and CA199, poor differentiation, and Lymph node metastasis were independent risk factors for the prognosis of gallbladder carcinoma after radical resection (P < 0.05). According to the 3-year survival rate, the survival rate of patients with liver 4B + 5 segment resection + cholecystectomy was higher than that of patients with 2 cm liver wedge resection + cholecystectomy (41.6% vs. 72.7%). Conclusion: Patients with T2b gallbladder cancer should be treated with liver segment IVb + V resection, which is helpful to improve the prognosis of patients and should be widely promoted.

Laparoscopic versus open in right posterior sectionectomy: a systematic review and meta-analysis.

BACKGROUND: Laparoscopic liver resection (LLR) is now widely adopted for the treatment of liver tumors due to its minimally invasive advantages. However, multicenter, large-sample population-based laparoscopic right posterior sectionectomy (LRPS) has rarely been reported. We aimed to assess the advantages and drawbacks of right posterior sectionectomy compared with laparoscopic and open surgery by meta-analysis. METHODS: Relevant literature was searched using the PubMed, Embase, Cochrane, Ovid Medline, and Web of Science databases up to September 12, 2021. Quality assessment was performed based on a modified version of the Newcastle-Ottawa Scale (NOS). The data were analyzed by Review Manager 5.3. The data were calculated by odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CI) for fixed-effects and random-effects models. RESULTS: The meta-analysis included seven studies involving 739 patients. Compared with open right posterior sectionectomy (ORPS), the LRPS group had lower intraoperative blood loss (MD - 135.45; 95%CI - 170.61 to - 100.30; P < 0.00001) and shorter postoperative hospital stays (MD - 2.17; 95% CI - 3.03 to - 1.31; P < 0.00001). However, there were no statistically significant differences between LRPS and ORPS regarding operative time (MD 44.97; P = 0.11), pedicle clamping (OR 0.65; P = 0.44), clamping time (MD 2.72; P = 0.31), transfusion rate (OR 1.95; P = 0.25), tumor size (MD - 0.16; P = 0.13), resection margin (MD 0.08; P = 0.63), R0 resection (OR 1.49; P = 0.35), recurrence rate (OR 2.06; P = 0.20), 5-year overall survival (OR 1.44; P = 0.45), and 5-year disease-free survival (OR 1.07; P = 0.88). Furthermore, no significant difference was observed in terms of postoperative complications (P = 0.08), bile leakage (P = 0.60), ascites (P = 0.08), incisional infection (P = 0.09), postoperative bleeding (P = 0.56), and pleural effusion (P = 0.77). CONCLUSIONS: LRPS has an advantage in the length of hospital stay and blood loss. LRPS is a very useful technology and feasible choice in patients with the right posterior hepatic lobe tumor.

Th22/IL-22 mediates the progression of HBV-related hepatocellular carcinoma via STAT3.

T helper cell 22 are abundant in Hepatitis B Virus-related hepatocellular carcinoma tissue, and the main cytokine interleukin 22 produced by Th22 cells is closely related to the initiation and development of HCC. Understanding the role of Th22/IL-22 in the progression of HBV-related HCC will facilitate new therapeutic development. Th22 cells were isolated from peripheral blood of healthy donors and co-cultured with HBV positive HepG2.2.15 cells. IL-22 secretion and HepG2.2.15 cell proliferation and apoptosis were monitored. Expressions of p-STAT3, Cyclin D1, Bcl-2, and cleaved caspase 3 were detected by Western blot analysis. Th22 cells significantly promoted the proliferation and inhibited the apoptosis of HepG2.2.15 cells; up-regulated expression of p-STAT3, Cyclin D1 and Bcl-2, and down-regulated cleaved caspase 3 in HepG2.2.15 cells. These effects were significantly attenuated when IL-22 and STAT3 was knockdown in Th22 and HepG2.2.15 cells, respectively. Our data suggests that HBV induces host Th22 cells to overexpress IL-22, which in turn triggers over-activation of STAT3 and its downstream signaling proteins to promote HCC progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-021-00517-9.

Safety and feasibility of laparoscopic left hepatectomy for the treatment of hepatolithiasis in patients with previous abdominal surgery.

BACKGROUND: The aim of the study was to compare the benefits and drawbacks of laparoscopic left hepatectomy (LLH) in patients with previous abdominal surgery (PAS) with those in patients without PAS and confirm the safety and feasibility of LLH as a treatment for patients with hepatolithiasis and PAS. MATERIALS AND METHODS: This retrospective comparative study included 111 patients who underwent LLH for hepatolithiasis (with PAS, n = 41; without PAS, n = 70) from August 2017 to August 2019. Patients' general information, surgical outcomes, hospital stay duration, hospitalisation cost, post-operative laboratory data and post-operative complications were evaluated. RESULTS: No statistically significant difference was noted in the post-operative laboratory data between patients with and without PAS (P > 0.05). Longer operative times were required for patients with PAS than for those without PAS (P = 0.025). Hospitalisation cost, hospital stay duration, blood loss, open conversion and post-operative complications were not significantly different between patients with and without PAS (P > 0.05). No cases of mortality were noted. CONCLUSIONS: LLH is a safe and feasible treatment for patients with hepatolithiasis and PAS.

Safety and feasibility for laparoscopic versus open caudate lobe resection: a meta-analysis.

BACKGROUND: Laparoscopic hepatectomy has been used widely due to its advantages as a minimally invasive surgery. However, multicenter, large-scale, population-based laparoscopic caudate lobe resection (LCLR) versus open caudate lobe resection (OCLR) has rarely been reported. We assessed the feasibility and safety of LCLR compared with OCLR using meta-analysis. METHODS: Relevant literature was retrieved using PubMed, Embase, Cochrane, Ovid Medline, Web of Science, CNKI, and WanFang Med databases up to July 30th, 2020. Multiple parameters of feasibility and safety were compared between the treatment groups. Quality of studies was assessed with the Newcastle-Ottawa Scale (NOS). The data were analyzed by Review Manager 5.3. Results are expressed as odds ratio (OD) or mean difference (MD) with 95% confidence interval (95% CI) for fixed- and random-effects models. RESULTS: Seven studies with 237 patients were included in this meta-analysis. Compared with OCLR, the LCLR group had a lower intraoperative blood loss (MD - 180.84; 95% CI - 225.61 to - 136.07; P < 0.0001), shorter postoperative hospital stays (MD - 4.38; 95% CI - 7.07 to - 1.7; P = 0.001), shorter operative time (MD - 50.24; 95% CI - 78.57 to - 21.92; P = 0.0005), and lower rates in intraoperative blood transfusion (OR 0.12; P = 0.01). However, there were no statistically significant differences between LCLR and OCLR regarding hospital expenses (MD 0.92; P = 0.12), pedicle clamping (OR 1.57; P = 0.32), postoperative complications (OR 0.58; P = 0.15), bile leak (P = 0.88), ascites (P = 0.34), and incisional infection (P = 0.36). CONCLUSIONS: LCLR has multiple advantages over OCLR, especially intraoperative blood loss and hospital stays. LCLR is a very useful technology and feasible choice in patients with caudate lobe lesions.

Comparative analysis of the safety and feasibility of laparoscopic versus open caudate lobe resection.

PURPOSE: Laparoscopic hepatectomy has been used widely in liver disease due to its advantages as a minimally invasive surgery. However, laparoscopic caudate lobe resection (LCLR) has been reported rarely. We aimed to investigate the safety and feasibility of LCLR by comparing it with open liver surgery. METHODS: A retrospective study was performed including all patients who underwent LCLR and open caudate lobe resection (OCLR) between January 2015 and August 2019. Twenty-two patients were involved in this study and divided into LCLR (n = 10) and OCLR (n = 12) groups based on preoperative imaging, tumor characteristics, and blood and liver function test. Patient demographic data and intraoperative and postoperative outcomes were compared between the two groups. RESULTS: There were no significant inter-group differences between gender, age, preoperative liver function, American Society of Anesthesiologists (ASA) grade, and comorbidities (P > 0.05). The LCLR showed significantly less blood loss (50 vs. 300 ml, respectively; P = 0.004), shorter length of hospital stay (15 vs. 16 days, respectively; P = 0.034), and shorter operative time (216.50 vs. 372.78 min, respectively; P = 0.012) than OCLR, but hospital expenses (5.02 vs. 6.50 WanRMB, respectively; P = 0.208) showed no statistical difference between groups. There was no statistical difference in postoperative bile leakage (P = 0.54) and wound infection (P = 0.54) between LCLR and OCLR. Neither LCLR nor OCLR resulted in bleeding or liver failure after operation. There were no deaths. CONCLUSION: LCLR is a very useful technology, and it is a feasible choice in selected patients with benign and malignant tumors in the caudate lobe.

The Safety and Feasibility of Laparoscopic Technology in Right Posterior Sectionectomy.

BACKGROUND: Laparoscopic hepatectomy has been accepted widely due to its advantages as a minimally invasive surgery, but laparoscopic right posterior sectionectomy (LRPS) has rarely been reported. We aimed to explore the safety and feasibility of LRPS by comparing it with open surgical approaches. MATERIALS AND METHODS: Between January 2014 and July 2019, 51 patients who underwent right posterior sectionectomy were enrolled in this study. The patients' characteristics, intraoperative details, and postoperative outcomes were compared between 2 groups. RESULTS: There were no statistically significant differences in the preoperative data. LRPS showed significantly less blood loss (P=0.001) and shorter hospital stay (P=0.002) than open right posterior sectionectomy, but hospital expenses (P=0.382), operative time (P=0.196), surgical margin (P=0.311), the rate of other complications, and the postoperative white blood cell count, alanine aminotransferase, aspartate aminotransferase, and total bilirubin showed no statistically significant differences between the 2 groups (P>0.05). For hepatocellular carcinoma, the results showed there were no differences in both disease-free survival (P=0.220) and overall survival (P=0.417) between the 2 groups. CONCLUSIONS: Our research suggests that LRPS is a safe and feasible surgical procedure that is efficient from an oncological point of view. It may be the preferred choice for lesions in the right posterior hepatic lobe.

CSN5 upregulates glycolysis to promote hepatocellular carcinoma metastasis via stabilizing the HK2 protein.

Aerobic glycolysis promotes metastasis and correlates with poorer clinical outcomes in hepatocellular carcinoma (HCC), but the controllers and mechanisms of abnormally activated glycolysis remain unclear. Herein, we demonstrated that the fifth component of the constitutive photomorphogenic 9 (COP9) signalosome complex (COPS5/CSN5) was a controller of glycolysis. For the first time, we found that CSN5 could influence the expression of glycolytic metabolism-associated proteins, especially hexokinase 2 (HK2), a glycolytic rate-limiting enzyme. In addition, we found that CSN5 was associated with HK2 overexpression in HCC tissues. Silencing CSN5 expression caused a decrease in the level of the HK2 protein, glucose uptake, glycolysis capacity and the production of glycolytic intermediates in HCC cells. Re-expression of HK2 rescued the decreased glycolytic flux induced by CSN5 knockdown, whereas inhibition of HK2 alleviated CSN5-enhanced glycolysis. Functionally, CSN5 regulated HCC cell invasion and metastasis via HK2-mediated glycolysis. Mechanistically, we demonstrated that CSN5 attenuated the ubiquitin-proteasome system-mediated degradation of HK2 through its deubiquitinase function. Inhibition of CSN5 kinase activity by curcumin decreased HK2 protein expression and glycolysis, repressed the metastasis of HCC cells in vitro and in vivo, and prolonged the survival time of tumor-bearing nude mice. Overall, our study identified CSN5 as a controller of glycolysis, and it may be a potential treatment target for HCC.

Safety and feasibility of laparoscopy technology in right hemihepatectomy.

Laparoscopic hepatectomy (LH) has been accepted widely owing to its advantages as a minimally invasive surgery; however, laparoscopic right hemihepatectomy (LRH) has rarely been reported. We aimed to compare the benefits and drawbacks of LRH and open approaches. Between January 2014 and October 2017, 85 patients with tumor and hepatolithiasis who underwent LRH (n = 30) and open right hemihepatectomy (ORH) (n = 55) were enrolled in this study. For tumors, LRH showed significantly better results with respect to blood loss (P = 0.024) and duration of hospital stay (P = 0.008) than ORH, while hospital expenses (P = 0.031) and bile leakage rate (P = 0.012) were higher with LRH. However, the operative time and rate of other complications were not significantly different between the two groups. However, for hepatolithiasis, there was less blood loss (P = 0.015) and longer operative time (P = 0.036) with LRH than with ORH. There were no significant difference between LRH and ORH in terms of hospital stay, hospital expenses, and complication rate (P > 0.05). Moreover, the postoperative white blood cell count, alanine aminotransferase level, aspartate aminotransferase level, and total bilirubin were not significantly different in both types of patients (P > 0.05). Our results suggest the safety and feasibility of laparoscopy technology for right hemihepatectomy in both tumor and hepatolithiasis patients.

Advantages of laparoscopic left hemihepatectomy: A meta-analysis.

BACKGROUND: Laparoscopic left hemihepatectomy (LLH) has been widely accepted as a minimally invasive alternative to open liver surgery. We assessed the benefits and drawbacks of LLH compared with open left hemihepatectomy (OLH) using meta-analysis. METHODS: Relevant literature was retrieved using PubMed, Embase, Cochrane, and Ovid Medline databases. Multiple parameters of efficacy and safety were compared between the treatment groups. Results are expressed as odds ratio (OD) or mean difference (MD) with 95% confidence interval (95% CI) for fixed- and random-effects models. RESULTS: The meta-analysis included 13 trials involving 1163 patients. Compared with OLH, LLH significantly reduced intraoperative blood loss (MD, -91.01; 95% CI, -139.12 to -42.89; P = .0002), transfusion requirement (OR, 0.24; 95% CI, 0.11-0.54; P = .0004), time to oral intake (MD, -0.80; 95% CI, -1.27 to -0.33; P = .0008), and hospital stay (MD, -3.94; 95% CI, -4.85 to -3.03; P < .0001). However, operative time; complications rate; and postoperative alanine transferase, albumin, and total bilirubin levels did not differ significantly between the 2 surgical groups (P > .05). For hepatolithiasis treatment, there were no significant differences in operative time, residual stones, stone recurrence, and complications rate between the groups (P > .05), but LLH resulted in lower incisional infection rate (OR, 0.44; 95% CI, 0.22-0.89; P = .02) than OLH. The LLH group demonstrated higher bile leakage rate (OR, 1.79; 95% CI, 1.14-2.81; P = .01) and incurred greater hospital costs (MD, 618.56; 95% CI, 154.47-1082.64; P = .009). CONCLUSIONS: LLH has multiple advantages over OLH and should thus be considered as the first choice for left hemihepatectomy.

SPAG5 promotes hepatocellular carcinoma progression by downregulating SCARA5 through modifying ß-catenin degradation.

BACKGROUND: The sperm-associated antigen 5 (SPAG5) plays a key role in controlling various cellular phenomena, including cell cycle progression and proliferation. However, the role of SPAG5 in hepatocellular carcinoma (HCC) remains unknown. METHODS: This study investigated the function and clinical significance of SPAG5 protein expression in hepatocellular carcinoma. We analyzed SPAG5 expression in surgical specimens from 136 HCC patients. The correlation between the clinical characteristics and prognosis was also determined. Furthermore, the SPAG5 was overexpressed in HCC cell and silenced with shRNA in HCC cells. Moreover, cell proliferation and apoptosis were measured using Edu assay and flow cytometry and a molecular mechanism of SPAG5 promotes HCC progression was explored. RESULTS: Herein, our study showed that upregulation of SPAG5 was detected frequently in primary HCC tissues, and was associated with significantly worse survival among the HCC patients. Multivariate analyses revealed that high SPAG5 expression was an independent predictive marker for the poor prognosis of HCC. SPAG5 silence effectively abolished the proliferation abilities of SPAG5 in vivo and in vitro, while induced apoptosis in HCC cells. Furthermore, our results indicate that SPAG5 promoted cell progression by decreasing SCARA5 expression, which has been reported to control the progression of HCC, and our data demonstrated that SCARA5 is crucial for SPAG5-mediated HCC cell progression in vitro and in vivo. Moreover, we found that the expression of SPAG5 and SCARA5 are inversely correlated in HCC tissues. In addition, we demonstrated that SPAG5 promoted progression in HCC via downregulating SCARA5 depended on the ß-catenin/TCF4 signaling pathway. Interestingly, the underlying mechanism is which SPAG5 regulates SCARA5 expression by modulating ß-catenin degradation. CONCLUSIONS: Taken together, our data provide a novel evidence for the biological and clinical significance of SPAG5 as a potential biomarker, and we demonstrate that SPAG5-ß-catenin-SCARA5 might be a novel pathway involved in HCC progression.

CSN5 Promotes Hepatocellular Carcinoma Progression by SCARA5 Inhibition Through Suppressing ß-Catenin Ubiquitination.

BACKGROUND: Increasing evidence has suggested that E3 Ubiquitin Ligase CSN5 is a newly characterized oncogene involved in various types of cancer. Scavenger receptor class A member 5 (SCARA5) is an important regulator of biological processes in cancer cells. However, the roles and relationship of CSN5 and SCARA5 in hepatocellular carcinoma (HCC) remain unclear. METHODS: We used RT-PCR, Western blot, and immunohistochemistry to measure CSN5 and SCARA5 expression in HCC tissues and corresponding non-tumor tissues. The CSN5 gene was overexpressed or silenced with lentiviral vectors in HCC cells. Cell proliferation was measured using CCK8 assay. And, the cell migration and invasion were analyzed by transwell assay. RESULTS: We found that the expressions of CSN5 and SCARA5 are inversely correlated in HCC tissues, and CSN5 expression levels were negatively correlated with the levels of SCARA5 in various HCC cells. Furthermore, we found that high level of CSN5 expression correlated closely with tumor TNM stage, tumor size, and venous metastasis, but low level of SCARA5 expression correlated closely with tumor TNM stage, tumor size, and venous metastasis. Additionally, survival of patients with lower expression of CNS5 was significantly better than that of higher expression group, but the survival of patients with higher expression of SCARA5 was significantly better than that of lower expression group. Moreover, knockdown of CSN5 increased SCARA5 expression and inhibited the proliferation and metastasis of HCC cells in vitro and in vivo. Finally, we found that CSN5 regulated SCARA5 expression by modulating ß-catenin. Mechanistically, our results indicate that CSN5 can decrease ß-catenin ubiquitination to enhance the protein expression of SCARA5 in HCC cells. CONCLUSIONS: Our data identified CSN5 as a critical oncoprotein involved in progression of HCC cells, which could serve as a potential therapeutic target in HCC patients.

Tumor repressor gene chondroadherin oppose migration and proliferation in hepatocellular carcinoma and predicts a good survival.

The molecular that used as prognosis and potential therapy target is urgently needed in hepatocellular carcinoma (HCC). In current work, we found the expression of CHAD (chondroadherin) was significantly reduced in hepatocellular carcinoma compared to the normal tissue, on both mRNA and protein levels, in three independent datasets. Survival analysis was implemented on these datasets, and low expression of CHAD was found to be significantly associated with poor survival. Furthermore, metastasis-averse HCC and metastasis-incline HCC group comparison, and protein abundance evaluation of normal-tumor-portal vein tumor thrombus pairs indicate that metastatic tendentiousness is reduced along with CHAD abundance. Correlation analysis was also carried out and CHAD was shown to be significantly associated with differentiation and metastasis. Multivariable cox regression analysis showed that CHAD expression is more important for prognosis, compared to the other clinical indicators. To facilitate the utilization of CHAD clinically, a nomogram was plotted to estimate the three-year survival rate. Functional assays testing the migration and proliferation ability following knock down of CHAD in two cell lines, SMMC7721 and HCCLM3, were performed and discovered that reduction of CHAD level significantly enhance both proliferation and migration in both cell lines. Gene Set Enrichment Analysis (GSEA) comparing the CHAD-low and CHAD-high group showed that KEGG signaling pathways including "focal adhesion", "ECM receptor interaction", and "regulation of actin cytoskeleton" were significantly enriched. In conclusion, as a potential prognostic biomarker, tumor suppressor gene CHAD represses migration and proliferation of hepatocellular carcinoma cells, probability via mediating cell-cell adhesion.

Comparison of the outcomes of hepatocellular carcinoma after hepatectomy between two regional medical centers in China and Japan.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant disease of the liver in China and Japan. The purpose of this study was to compare the outcomes of HCC patients after hepatectomy between two regional medical centers in China and Japan. METHODS: Data on HCC after hepatectomy were collected from January 2005 to December 2014 from Nagasaki University Hospital in Nagasaki, Japan and the Second Affiliated Hospital of Nanchang University in Nanchang, China. The patient and tumor characteristics, HCC etiology, and overall survival rates after hepatectomy were investigated. RESULTS: Two hundred patients in the Nagasaki group and 238 patients in the Nanchang group were diagnosed with HCC and underwent hepatectomy. The major underlying liver diseases were hepatitis C infection (32%, 64/200) and nonalcoholic steatohepatitis (NASH) (34.5%, 69/200) in the Nagasaki group, while in the Nanchang group, hepatitis B infection (79.4%, 189/238) was the dominant etiology. Large tumors (> 5 cm), the presence of a tumor capsule and a high alpha-fetoprotein value (≥ 400 U/L) were more frequently observed in the Nanchang group as compared with the Nagasaki group (p < 0.05). According to an outcome analysis, the Nanchang patients showed worse survival rates as compared with Nagasaki patients, particularly those with American Joint Committee on Cancer stages I and III due to the aggressive character of HCC in the Nanchang group. CONCLUSION: There are significant differences in the clinicopathologic features and outcomes of HCC patients from Japan and China. These differences may impact the eligibility for potentially curative therapy and the prognosis of patients with HCC.

Rock2 promotes the invasion and metastasis of hepatocellular carcinoma by modifying MMP2 ubiquitination and degradation.

Rho-associated coiled-coil-containing protein kinase 2 (Rock2) is a downstream effector of Rho that plays an important role in the tumorigenesis and progression of hepatocellular carcinoma (HCC). Matrix metalloproteinase 2 (MMP2) is a master regulator of tumor metastasis. In this study, we investigated the collections of Rock2 and MMP2 in HCCs and determined the potential role and molecular mechanism of Rock2 in MMP2-mediated invasiveness and metastasis. We found that Rock2 and MMP2 were markedly overexpressed in HCCs compared with the corresponding adjacent tissues, where a positive correlation in their expression was found. The knockdown of Rock2 significantly decreased MMP2 expression and inhibited the invasion and metastasis of HCC in vitro and in vivo. Additionally, the upregulation of MMP2 rescued the decreased migration and invasion induced by the knockdown of Rock2, whereas the knockdown of MMP2 decreased Rock2-enhanced HCC migration and invasion. Mechanistically, Rock2 stabilized MMP2 by preventing its ubiquitination and degradation. Together, our results link two drivers of invasion and metastasis in HCC and identify a novel pathway for MMP2 control.

Inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma: in vitro and in vivo studies.

OBJECTIVE: To investigate the inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma both in vitro and in vivo, which may be a potential agents with sensitivity and targeting ability for human hepatocellular cancer. METHODS: Humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate was previously constructed using ribosome display technology and antibody conjugate technology. In this combined in vitro and in vivo study, the inhibitory effects of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on tumor growth, invasion, and metastasis was observed with human liver carcinoma cell line Bel7402 and normal cell L02 by MTT assay, Tanswell assay, Hochest33258 staining, and DNA ladder analysis. The anticancer activity and distribution of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles was then verified in a mouse model of Bel7402 xenografts. RESULTS: Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles significantly inhibited the proliferation of Bel7402 in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay while had almost no effects on L02 cells. And the apoptosis inducing effects were proved by Hochest33258 staining and DNA ladder analysis. Transwell assay found that the drug also inhibited the metastasis ability of tumor cells. Furthermore, anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles significantly delayed the growth of Bel7402 xenografts after administration (92.9%), followed by As2O3-stealth nanoparticles, anti-VEGFR-2 ScFv, and As2O3 (61.4%, 58.8%, 20.5%, P<0.05). The concentration of As2O3 in anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles group was more selectively. CONCLUSIONS: Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles is a potent and selective anti-hepatocellular carcinoma agent which could inhibit the growth of liver cancer as a targeting agent both in vitro and in vivo and also significantly inhibit angiogenesis.

Laparoscopic hepatectomy is associated with a higher incident frequency in hepatolithiasis patients.

PURPOSES: The primary concern regarding laparoscopic hepatectomy in hepatolithiasis patients is surgical safety, which may be high in current practice. METHODS: Hepatolithiasis patients who underwent laparoscopic and laparotomic hepatectomies were retrospectively studies after being matched for age, location of gallstones, liver resection and underlying liver conditions at a ratio of 1:1 (n = 44 in each group). The rates of intraoperative incidents and postoperative complications were examined using validated classification and grading systems. The primary outcome measure was the procedure-related complication/mortality rate. RESULTS: Laparoscopy was converted to open surgery in three patients (6.8 %). The length of the operation for laparoscopic hepatectomy was significantly longer than that for laparotomic hepatectomy (277.5 min [range, 190-410 min] vs. 212.5 min [140-315 min], P < 0.001). The two groups had similar intraoperative blood loss (367.5 mL [150-1200 mL] vs. 392.5 mL [200-1400 mL], P > 0.05) and transfusion frequencies (13.6 vs. 18.2 %, P > 0.05). The laparoscopy group had a higher percentage of patients with at least one intraoperative incident compared with the laparotomy group (22.7 vs. 6.8 %; P < 0.05). Vascular events occurred in nine patients (20.5 %) undergoing laparoscopy and two patients (4.5 %) undergoing laparotomy (OR 5.4 [95 %CI, 1.1-26.7], P < 0.05). CONCLUSIONS: Laparoscopic hepatectomy is associated with a higher risk of intraoperative vascular incidents in hepatolithiasis patients compared wit laparotomy.

Simultaneous determination of loratadine and pseudoephedrine sulfate in human plasma by liquid chromatography-electrospray mass spectrometry for pharmacokinetic studies.

To support the pharmacokinetic and bioavailability study of an extended-release loratadine (LOR)/pseudoephedrine sulfate (PES) tablet, a high performance liquid chromatographic-electrospray ionisation-mass spectrometric method (LC-MS) was developed for the simultaneous determination of LOR and PES in human plasma. Diazepam (DP) and phenylpropanolamine (PPA) were used as internal standards for LOR and PES, respectively. Analytes were extracted from alkalized human plasma by liquid/liquid extraction using ethyl ether. Chromatographic separation was performed on an ODS column at flow rate of 0.2 ml/min. The total chromatographic run time was 10.5 min with the retention time of 7.1 min and 6.2 min for LOR and DP, respectively, and 2.2 min for both of PES and PPA. The LOQ was 10 pg/ml and 50 pg/ml for LOR and PES, respectively. The method is accurate and precise enough for its intended purpose.