Prognosis after hepatectomy for primary liver cancer of segment 7 or 8 / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the results of surgical treatment for primary liver cancer of segment VII or VIII.</p><p><b>METHODS</b>The clinical data of 149 patients with primary liver cancer who underwent hepatectomy between January 2005 and December 2010 was retrospectively analyzed. There were 120 male and 29 female patients, aging from 19 to 75 years with a mean of 53.1 years. Among 149 patients, tumors were located at segment VII, VIII or several segments containing VII or VIII (VII/VIII group) in 53 patients, located at other segments (non-VII/VIII group) in 96 patients. The results of surgical treatment for VII/VIII group and non-VII/VIII group were compared by using t test, χ(2) test, Kaplan-Meier survival analysis and Cox proportion hazard regression analysis.</p><p><b>RESULTS</b>Right liver lobe was turned over completely in VII/VIII group, hepatic lobe which tumor was located at was not or partly turned over in non-VII/VIII group. Compared with non-VII/VIII group, VII/VIII group had longer operative time ((215 ± 68) min vs. (123 ± 36) min, t = 2.860, P = 0.01). No significant difference was found for tumor size, tumor number, tumor encapsulation, microvascular invasion, Edmondson grade, pTNM stage, intraoperative blood loss, blood transfusion rate, R0 resection rate and postoperative complication rate between two groups. The cumulative 1-, 3-, and 5-year overall survival rates were 74.6%, 42.3%, 15.4% respectively, in VII/VIII group, and 89.3%, 63.0%, 40.4% respectively, in non-VII/VIII group (χ(2) = 13.501, P = 0.000). Univariate and multivariate analysis of prognostic factors indicated that tumor location (tumor was located at segment VII or VIII) had unfavorable prognostic influence on overall survival (χ(2) = 10.329, P = 0.001; HR = 1.693, 95%CI: 1.232 - 2.694, P = 0.013).</p><p><b>CONCLUSION</b>The results of surgical treatment for primary liver cancer located at segment VII or VIII are worse than that located at other segments.</p>

Effects of celecoxib combined with fluvastatin on tumor growth and cell apoptosis in a xenograft model of hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate effects of celecoxib (a selective cox-2 inhibitor)combined with fluvastatin (a HMG-CoA reductase inhibitor) on tumor growth and cell apoptosis in hepatocellular carcinoma xenograft in nude mice.</p><p><b>METHODS</b>Hepatocellular carcinoma BEL-7402 cells were inoculated subcutaneously into the left armpit of nude mice, the mice (n = 32) were then randomly divided into 4 groups: the control group, the celecoxib group,the fluvastatin group and the combination group. At the end of the study, Tumor Tissues were collected for analysis. Cell apoptosis was determined by flow cytometry analysis and TUNEL assay. Akt, p-Akt and survivin protein levels were measured by Western blot. Statistical comparisons were made using factorial analysis of variance (ANOVA) and multiple comparisons between each two groups were calculated using SNK-q test.</p><p><b>RESULTS</b>The combination of Celecoxib and fluvastatin resulted in a greater inhibition of tumor growth than either agent alone, the tumor inhibitory rate was 34.0% in the Celecoxib group, 25.0% in the fluvastatin group and 72.2% in the combination group. The percentages of TUNEL--positive cancer cells in the celecoxib and fluvastatin alone treatment groups were 8.5%+/-1.4% and 9.4%+/-1.7% respectively as compared to the control group which was 3.5%+/-0.8%. Combination therapy showed a significantly greater increase in tumor cell apoptosis in comparison with the control and single-therapy groups (apoptotic index: 19.4%+/-3.0%; P value is less than 0.01 versus celecoxib or fluvastatin groups). The results of flow cytometry analysis also showed the same tendency. a small number of apoptotic cells were detected in the control tumours (4.1%+/-1.6%), whereas a large number of apoptotic cells were detected in tumours treated with celecoxib (9.1%+/-2.1%) or fluvastatin (10.1%+/-2.3%) alone; and the combination therapy resulted in even more apoptotic cells (23.6%+/-5.8%; P value is less than 0.01 versus celecoxib or fluvastatin groups). Western blot analysis demonstrated that the combination of celecoxib and fluvastatin significantly down-regulated p-Akt (0.23+/-0.08 versus 1.12+/-0.07 and surviving (0.50+/-0.07 versus 1.47+/-0.19) in BEL-7402 tumours compared with the control (P value is less than 0.01 for all).</p><p><b>CONCLUSION</b>The present study provided evidence that treatment with celecoxib in combination with fluvastatin resulted in the inhibition of HCC tumour growth in an in vivo mouse model.</p>

Expression of estrogen receptor α in hepatitis B-related hepatocellular carcinoma and its clinical significance / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the expression and its clinical significance of estrogen receptor (ERα) and phosphorylated estrogen receptor (p-ERα) in patients with hepatocellular carcinoma. The associations between ERα, p-ERα and IL-6 were also analyzed.</p><p><b>METHODS</b>Immunohistochemistry was used to detect the expression of ERα, p-ERα and IL-6 in tumor tissues from 77 cases with hepatocellular carcinoma. The relations between ERα and the clinical pathological parameters and prognosis were also analyzed.</p><p><b>RESULTS</b>The positive rates of ERα, p-ERα and IL-6 in hepatocellular carcinoma were 39.0% (30/77), 45.4% (35/77) and 72.7% (56/77), respectively. The expression of ERα and p-ERα were negatively correlated with the expression of IL-6 (r=-0.468, P<0.01; r=-0.370, P<0.01, respectively). The positive rate of ERα in patients with tumor size≤5 cm, serum level of alpha-fetoprotein<400 µg/L, with complete encapsulation and non-microvascular invasion was significantly higher than those with tumor size>5 cm, serum level of alpha-fetoprotein≥400 µg/L, non-complete encapsulation and with microvascular invasion (all P<0.05). The overall survival rates of ERα-positive and ERα-negative patients were 66.7% and 23.4% (P<0.05). And the disease-free survival rates of ERα-positive and ERα-negative patients were 83.3% and 57.4% (P<0.05).</p><p><b>CONCLUSIONS</b>The tumor biological features of ERα-positive patients are better than that of ERα-negative patients. The role of ERα in hepatocellular carcinoma may be related to IL-6 level.</p>

Prevention of hepatic tumor growth and metastasis in rats with rapamycin / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To test the effect of rapamycin (RAPA) on hepatic tumor growth and metastasis in Sprague-Dawley (SD) rat model and explore the possible mechanism.</p><p><b>METHODS</b>SD rat hepatocellular carcinoma (HCC) model with metastatic potential was induced by diethylnitrosamine (DEN) and N-nitrosomorpholine (NMOR). 120 SD rats were randomized into four groups 16 weeks after DEN and NMOR treatment, and received 4-week intraperitoneal injection of RAPA (1.5 or 4.5 mg x kg(-1) x d(-1)), CsA (25 mg x kg(-1) x d(-1)) or equal volume of 0.9% saline, respectively. Tumor growth and metastasis were checked after the 4-week treatment. Serum vascular endothelial growth factor (VEGF) was determined by enzyme-linked immunosorbent assay (ELISA). Antiangiogenetic effects were assessed by CD34 immunostaining. The levels of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and VEGF proteins and mRNAs were detected by immunohistochemistry, western blot and reverse transcriptase-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>The mean liver weight (5.58% +/- 0.42% and 5.69% +/- 0.74%), the metastatic liver nodules (5.12 +/- 0.68 and 5.67 +/-1.12), the metastasis lung nodules (0.43 +/- 0.11 and 0.45 +/- 0.83), and the lung metastasis rate (17.2% and 14.8%) were lower in rats treated with RAPA 1.5 mg x kg(-1) x d(-1) or 4.5 mg x kg(-1) x d(-1) than those in rats treated with saline, which were 10.42% +/- 1.86%, 12.36 +/- 3.45, 1.81 +/- 0.3 and 50.0% respectively (P < 0.01 or P < 0.05). The intratumoral microvessel density (MVD), serum VEGF, and the levels of HIF-1 alpha and VEGF were lower in RAPA-treated rats than those in control rats. However, CsA-treated rats showed an opposite trend compared with the RAPA-treated rats.</p><p><b>CONCLUSION</b>RAPA can repress the expression of angiogenesis-promoting factors HIF-1 alpha and VEGF, and significantly inhibits the growth and metastasis of HCC.</p>

Effects of high metastatic potential hepatocellular carcinoma cell-binding peptide on the invasion and metastasis of liver cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the effects of specific peptide (AWYPLPP peptide) binding to high metastatic potential human hepatocellular carcinoma (HCC) cells on the invasion and metastasis of liver cancer.</p><p><b>METHODS</b>The effects of AWYPLPP peptide on the invasion, migration, proliferation and adhesion of high metastatic potential human HCC cell line (HCCLM3) were evaluated in vitro by Matrigel invasion assay, migration assay, MTT assay and adhesion assay. The effect of AWYPLPP peptide on lung metastasis of HCC in vivo was evaluated in male nude mice with subcutaneously implanted HCCLM3 cells.</p><p><b>RESULTS</b>Incubation with the AWYPLPP peptide, but not the control peptide, resulted in a concentration-dependent increase of invasion ability in HCCLM3 cells at the concentration of 0.1 to 100 micromol/L. At any concentration used for the invasion assay, the peptide had no effect on cell migration, proliferation and adhesion. After 30 days of transplantation, eight of nine (88.9%) mice in the AWYPLPP peptide group showed obvious lung metastasis. The metastatic rate of lung metastasis was significantly increased in the AWYPLPP peptide group compared with that in the control group. There was no significant difference among the weights of primary tumor in the PBS, control peptide and AWYPLPP peptide groups.</p><p><b>CONCLUSION</b>AWYPLPP peptide can promote in vitro invasion and in vivo lung metastasis of high metastatic potential human HCC cells. Identification of the receptor for AWYPLPP peptide binding may provide new insights into the molecular mechanism underlying HCC invasion and metastasis as well as new targets for intervention.</p>

Expression of TFPI-2 gene in pancreatic carcinoma and its prognostic significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the expression of TFPI-2 gene in pancreatic carcinoma, and to evaluate its prognostic significance in patients with pancreatic carcinoma.</p><p><b>METHODS</b>Reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of TFPI-2 mRNA and protein in the pancreatic carcinoma tissue samples from 41 patients. The correlation of its expression with clinicopathological features and its prognostic significance were analyzed.</p><p><b>RESULTS</b>The expression of TFPI-2 mRNA and protein in moderately or poorly differentiated pancreatic carcinoma tissues, or in cases with nerve-involvement, lymph node and blood vessel invasion was significantly lower than that in the highly differentiated one, or without nerve involvement, or neither lymphatic nor blood vessel invasion (P < 0.05). The median survival time of patients with high expression of TFPI-2 (12.0 months) was significantly longer than that with low expression of TFPI-2 (5.1 months, P < 0.05). The Cox model analysis showed that the expression of TFPI-2 was an independent marker for prognosis in patients with pancreatic carcinoma.</p><p><b>CONCLUSION</b>The expression of TFPI-2 is correlated with clinical stage and differentiation of pancreatic carcinoma, and can be used as a prognostic marker for pancreatic carcinoma.</p>

Small-diameter prosthetic H-graft portacaval shunts in the treatment of portal hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Portasystemic shunts, especially total shunts, are effective tools for reducing portal pressure and controlling variceal bleeding but lead to high risk of encephalopathy and accelerating liver failure. The purpose of this study is to evaluate the clinical effects of small-diameter expanded polytetrafluoroethylene (ePTFE) H-graft portacaval shunts in the treatment of portal hypertension.</p><p><b>METHODS</b>Thirty-one patients with portal hypertension were treated with ePTFE small-diameter H-graft portacaval shunts from December 1995 to April 2002. Twenty-one had externally ringed grafts and 10 had non-ringed grafts; 20 had 10 mm diameter grafts and 11 had 8 mm grafts. The left gastric artery and coronary vein were ligated in 22 patients. Additionally, 6 patients underwent pericardial devascularization, and splenectomies were performed on 30 patients.</p><p><b>RESULTS</b>An average decrease of free portal pressure (FPP) from (32.13 +/- 4.86) cmH2O before shunting to (12.55 +/- 5.57) cmH2O after shunting was observed. Portal blood flow was reduced by 1/3 compared with the levels measured before shunting. Twenty-eight patients survived after the operation, and no upper gastrointestinal rebleeding occurred in the follow-up period (40.2 months on average). We lost contact with one patient. Color Doppler ultrasonography and/or portography revealed the shunts to be patent in 28 cases and occluded in 2 (6.4%) cases. Encephalopathy developed in 4 patients (12.9%).</p><p><b>CONCLUSION</b>Small-diameter ePTFE H-graft portacaval shunts can effectively reduce portal pressure. Moreover, the majority of the hepatopetal flow from the portal vein can be adequately maintained. The reinforced shunts may achieve a higher rate of patency. Morbidity from encephalopathy was less frequent than in patients receiving total shunts. Small-diameter H-graft portacaval shunts are also effective in preventing recurrent variceal bleeding.</p>