Xian-Qiang Wang

Galectin-9 acts as a prognostic factor with antimetastatic potential in hepatocellular carcinoma.

Considerable research has been conducted concerning galectin-9 and carcinomas, but little information is available about any relation with the hepatocellular carcinoma. In this study, we employed a small interfering RNA (siRNA) targeting galectin-9 to down-regulate the expression in HepG2 cells. As a result, after galectin-9 expression was reduced, cell aggregation was suppressed, while other behaviour such as the proliferation, adhesion and invasion to ECM, cell-endothelial adhesion and transendothelial invasion of the cells were markedly enhanced. When tumors of 200 patients with hepatocellular carcinoma were tested for galectin-9 expression by immunohistochemistry, binding levels demonstrated intimate correlations with the histopathologic grade, lymph node metastasis, vascular invasion and intrahepatic metastasis (P<0.05). Moreover, survival analysis indicated that patients with galectin-9 expression had much longer survival time than those with negative lesions, and the Log-rank test indicated that this difference was statistical significant (P<0.0001). The Cox proportional hazards model suggested that negative galectin-9 expression in hepatocellular carcinoma represented a significant risk factor for patient survival. We propose that galectin-9 might be a new prognostic factor with antimetastatic potential in patients with hepatocellular carcinoma.

Risk scoring system and predictor for clinically relevant pancreatic fistula after pancreaticoduodenectomy.

AIM To establish a scoring system to predict clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). METHODS The clinical records of 921 consecutive patients who underwent PD between 2008 and 2013 were reviewed retrospectively. Postoperative pancreatic fistula (POPF) was defined and classified by the international study group of pancreatic fistula (ISGPF). We used a logistic regression model to determine the independent risk factors of CR-POPF and developed a scoring system based on the regression coefficient of the logistic regression model. The optimal cut-off value to divide the risk strata was determined by the Youden index. The patients were divided into two groups (low risk and high risk). The independent sample t test was used to detect differences in the means of drain amylase on postoperative day (POD) 1, 2 and 3. The optimal cut-off level of the drain amylase to distinguish CR-POPF from non-clinical POPF in the two risk strata groups was determined using the receiver operating characteristic (ROC) curves. RESULTS Grade A POPF occurred in 106 (11.5%) patients, grade B occurred in 57 (6.2%) patients, and grade C occurred in 32 (3.5%) patients. A predictive scoring system for CR-POPF (0-6 points) was constructed using the following four factors: 1 point for each body mass index ≥ 28 [odds ratio (OR) = 3.86; 95% confidence interval (CI): 1.92-7.75, P = 0.00], soft gland texture (OR = 4.50; 95%CI, 2.53-7.98, P = 0.00), and the difference between the blood loss and transfusion in operation ≥ 800 mL (OR = 3.45; 95%CI, 1.92-7.75, P = 0.00); and from 0 points for a 5 mm or greater duct diameter to 3 points for a less than 2 mm duct (OR = 8.97; 95%CI: 3.70-21.77, P = 0.00). The ROC curve showed that the area under the curve of this score was 0.812. A score of 3 points was suggested to be the best cut-off value (Youden index = 0.485). In the low risk group, a drain amylase level ≥ 3600 U/L on POD3 could distinguish CR-POPF from non-clinical POPF (the sensitivity and specificity were 75% and 85%, respectively). In the high risk group, the best cut-off was a drain amylase level of 1600 (the sensitivity and specificity were 77 and 63%, respectively). CONCLUSION A 6-point scoring system accurately predicted the occurrence of CR-POPF. In addition, a drain amylase level on POD3 might be a predictor of this complication.

Poor prognosis for hepatocellular carcinoma with transarterial chemoembolization pre-transplantation: Retrospective analysis

AIM To investigate whether transarterial chemoembolization (TACE) before liver transplantation (LT) improves long-term survival in hepatocellular carcinoma (HCC) patients. METHODS A retrospective study was conducted among 204 patients with HCC who received LT from January 2002 to December 2010 in PLA General Hospital. Among them, 88 patients received TACE before LT. Prognostic factors of serum α-fetoprotein (AFP), intraoperative blood loss, intraoperative blood transfusion, disease-free survival time, survival time with tumor, number of tumor nodules, tumor size, tumor number, presence of blood vessels and bile duct invasion, lymph node metastasis, degree of tumor differentiation, and preoperative liver function were determined in accordance with the Child-Turcotte-Pugh (Child) classification and model for end-stage liver disease. We also determined time of TACE before transplant surgery and tumor recurrence and metastasis according to different organs. Cumulative survival rate and disease-free survival rate curves were prepared using the Kaplan-Meier method, and the log-rank and χ(2) tests were used for comparisons. RESULTS In patients with and without TACE before LT, the 1, 3 and 5-year cumulative survival rate was 70.5% ± 4.9% vs 91.4% ± 2.6%, 53.3% ± 6.0% vs 83.1% ± 3.9%, and 46.2% ± 7.0% vs 80.8% ± 4.5%, respectively. The median survival time of patients with and without TACE was 51.857 ± 5.042 mo vs 80.930 ± 3.308 mo (χ(2) = 22.547, P < 0.001, P < 0.05). The 1, 3 and 5-year disease-free survival rates for patients with and without TACE before LT were 62.3% ± 5.2% vs 98.9% ± 3.0%, 48.7% ± 6.7% vs 82.1% ± 4.1%, and 48.7% ± 6.7% vs 82.1% ± 4.1%, respectively. The median survival time of patients with and without TACE before LT was 50.386 ± 4.901 mo vs 80.281 ± 3.216 mo (χ(2) = 22.063, P < 0.001, P < 0.05). TACE before LT can easily lead to pulmonary or distant metastasis of the primary tumor. Although there was no significant difference between the two groups, the chance of metastasis of the primary tumor in the group with TACE was significantly higher than that of the group without TACE. CONCLUSION TACE pre-LT for HCC patients increased the chances of pulmonary or distant metastasis of the primary tumor, thus reducing the long-term survival rate.

Integrin αvβ6 sustains and promotes tumor invasive growth in colon cancer progression

AIM To detect the mechanism by which colon tumor escapes the growth constraints imposed on normal cells by cell crowding and dense pericellular matrices. METHODS An immunohistochemical study of integrin αvβ6 and matrix metalloproteinase-9 (MMP-9) was performed on tissue microarrays of 200 spots, including 100 cases of colon tumors. RESULTS High immunoreactivity for αvβ6 (73.7%; 28/38) and MMP-9 (76.5%; 52/68) was observed in invasive tumor portions. Furthermore, the effects of integrin αvβ6 on tumor invasive growth in nude mice were detected. Tumor invasive growth and high expression of both αvβ6 and MMP-9 were only seen in tumors resulting from WiDr cells expressing αvβ6 in the tumorigenicity assay. Flow cytometry was applied to analyze αvβ6 expression in colon cancer WiDr and SW480 cells. The effects of cell density on αvβ6 expression and MMP-9 secretion were also detected by Biotrak MMP-9 activity assay and gelatin zymography assay. High cell density evidently enhanced αvβ6 expression and promoted MMP-9 secretion compared with low density. CONCLUSION Integrin αvβ6 sustains and promotes tumor invasive growth in tumor progression via a self-perpetuating mechanism. Integrin ανβ6-mediated MMP-9 secretion facilitates pericellular matrix degradation at high cell density, which provides the basis of invasive growth.

Portal inflow preservation during portal diversion in small-for-size syndrome

AIM To investigate the impact of portal inflow on liver remnants in a stable pig model of small-for-size syndrome. METHODS Twenty pigs underwent mesocaval shunt (MCS) surgery followed by 85%-90% hepatectomy. The control group had no shunt placement; the S1 group had portal flow maintained at an average of 2.0 times the baseline values; and the S2 group had portal flow maintained at an average of 3.2 times the baseline flow. The effect of portal functional competition on the liver remnant was investigated for 48 h postoperatively. Data were presented as mean ± SD. Statistical significance was determined using Students t test (SPSS, Chicago, IL, United States). Values of P < 0.05 were considered statistically significant. RESULTS At 24 h after hepatectomy, biochemical and histological changes were not significantly different between the S1 and S2 groups, but changes in both sets of variables were significantly less than in the control group. At 48 h, biochemical and histological changes were significantly less in the S2 group than in the S1 or control group. The regeneration index was significantly higher in the S2 group than in the S1 group, and was similar to that in the control group. Apoptosis index, serum lipopolysaccharide, and bacterial DNA levels were significantly lower in the S2 group than in the other two groups. CONCLUSION Diversion of portal inflow using MCS reduces portal overflow injury. Excessive diversion of portal inflow inhibits liver regeneration following major hepatectomy. Maintaining portal inflow at an average of 3.2 times above baseline helps promote hypertrophy of the liver remnant and reduce apoptosis.

Hepatoma-derived growth factor promotes growth and metastasis of hepatocellular carcinoma cells

We aimed to elucidate the effects of hepatoma‐derived growth factor (HDGF) on growth and metastasis of hepatocellular carcinoma (HCC) cells. Tissue microarrays with 236 HCC specimens and 18 extrahepatic metastases were utilized to detect the HDGF expression by immunohistochemistry. Meanwhile, HDGF expressions in HCC cell lines with different metastatic potentials were examined using immunofluorescence staining, real‐time PCR and western blotting. After HDGF silencing, the growth and metastatic potentials of HCC cells were evaluated by soft agar assay, invasion assay, together with tumorigenicity assay in nude mice. The gelatin zymography was performed by detecting MMP‐2 and MMP‐9 levels. Additionally, western blotting was conducted to determine the levels of total and phosphorylated ERK1/2, JNK, p38 and Akt. The results showed that HDGF was overexpressed in HCC metastasis tumour, and the expression increased with the differentiation degree of tumours (Grade I 44.0%, Grade II 48.4% and Grade III 65.6%). Consistently, HDGF levels were positively associated with the metastatic capability of HCC cells (MHCC97L < MHCC97H < HCCLM3). The growth and metastasis were suppressed by HDGF‐siRNA. Gelatinolytic activities were enhanced in the three metastatic HCC cell lines, but had no significant difference among them. The tumourigenicity and metastatic capability of HCCLM3 cells in nude mice were inhibited after silencing HDGF. Meanwhile, HDGF‐siRNA specifically suppressed the total and phosphorylated protein levels of ERK1/2, while not JNK, p38 and Akt. In conclusion, HDGF was overexpressed in HCC patients and cells, and HDGF might be closely correlated with HCC metastasis via regulating ERK signalling pathway. Copyright