Role of chemokine CCL28 in hypoxia-induced migration of hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the role of CCL28 in hypoxia-induced cell migration of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Resected liver tissues from 50 HCC patients were subjected to real-time (rt)-PCR analysis to evaluate the mRNA expression levels of the hypoxia-induced factor HIF-1a and the chemokine CCL28. Patient data on treatment and outcome were analyzed. The human HCC cell lines HepG2 and HCCLM3 were used to investigate effects of hypoxic conditions on HIF-1a and CCL28 expressions by rt-PCR, western blotting, and enzyme-linked immunoassay. The CCL28-mediated effects of hypoxic conditions on cell mobility and invasion were assessed by trans-well and matrigel assays, respectively, in HCCLM3 with CCL28 expression silenced by small-interfering (si)RNA transfection. Spearman's rank test was used to assess the correlation between CCL28 and effects on disease- and treatment-related factors.</p><p><b>RESULTS</b>The mRNA levels of CCL28 (0.025 +/- 0.075) were found to be strongly correlated with HIF-1a(0.065 +/- 0.098) in human clinical samples of HCC (r = 0.595, P less than 0.01), with higher expressions of both related to recurrence after surgery (P = 0.011 and 0.019, respectively). In vitro hypoxic conditions stimulated HIF-1a and CCL28 expression in a time-dependent manner in both HepG2 (HIF-1a: F = 873.5; CCL28: F = 151.6) and HCCLM3 (HIF-1a: F = 964.5; CCL28: F = 285.8) (all P less than 0.01). siRNA inhibition of CCL28 in HCCLM3 cells led to a significant reduction in hypoxia-induced invasion and migration (all P = 0.011).</p><p><b>CONCLUSION</b>Chemokine CCL28 expression is up-regulated in human HCC and under in vitro hypoxic conditions, and may play an important role in hypoxia-induced HCC migration and invasion.</p>

Effect of postoperative adjuvant transarterial chemoembolization on late recurrence of hepatocellular carcinoma after radical resection / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To identify the effect of postoperative adjuvant transarterial chemoembolization (TACE) on late recurrence of hepatocellular carcinoma (HCC) patients after radical resection.</p><p><b>METHODS</b>From year 2001 to 2007, 2436 HCC patients underwent radical resection were retrospectively selected. Patients underwent resection only were classified into control group, while those received adjuvant TACE within 2 months after operation were classified into intervention group. Patients were further stratified into those with tumor<or=5 cm and presenting low or high risk factors for recurrence, as well as tumor>5 cm and presenting low or high risk factors for recurrence. Patients with single tumor and without microscopic tumor thrombus were defined as low risk for recurrence; otherwise they were defined as high risk. The effect of adjuvant TACE on late (>2 years) recurrence was evaluated.</p><p><b>RESULTS</b>Recurrence rates of tumor<or=5 cm and presenting low, high risk factors for recurrence, as well as tumor>5 cm and presenting low, high risk factors for recurrence at 2-year after resection were 20.38%, 33.06%, 30.54% and 50.82%, respectively in the control group, compared with 25.41%, 39.61%, 40.55% and 51.57%, respectively in the intervention group; there were no significant differences between intervention group and control group in each stratum. For patients recurred or died within the first 2 years after resection, the median survival of tumor>5 cm and presenting high risk factors for recurrence was 24 months in the intervention group and 12 months in the Control group. Only in this subgroup, the survival curve of the intervention group was significantly higher than that compared to the control group. For patients who remained recurrence free and survived within the first 2 years after resection, there were no significant differences in the recurrence curves between the intervention group and control group in each stratum; while cumulative survival rates in the subgroup of patients with tumor size is less than or equal to 5 cm and presenting low risk factors for recurrence were 93.95%, 91.50% and 88.42% respectively in the control group, compared with 91.70%, 81.32% and 78.19% respectively in the intervention group at 3-, 4- and 5-year after resection (P=0.0062); for other subgroups, there were no significant differences in the survival curves between the intervention group and the control group in each stratum. Cox regression model suggested adjuvant TACE was not an independent risk factor for late recurrence; however, it might have negative effect on survival [hazard ratio (HR)=1.50, P=0.062] for those patients (especially patients with tumor is less than or equal to 5 cm and presenting low risk factors for recurrence).</p><p><b>CONCLUSIONS</b>The value of adjuvant TACE was mainly due to its therapeutic actions on residual tumor or early recurrence. It had no effect on postponing or eliminating late recurrence; moreover, it could be a risk rather than a benefit in patients at low risk for recurrence (especially those with tumor is less than or equal to 5 cm and presenting low risk factors for recurrence).</p>

Therapeutic efficacy and prognostic factors of sorafenib treatment in patients with unresectable primary hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and analyze the prognostic factors of sorafenib treatment in patient with unresectable primary hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>During the period from December 2005 to March 2009, 50 patients with unresectable primary HCC of Child-Pugh status A were treated with sorafenib (400 mg, Bid). The tumor response was evaluated with CT or MRI imaging every 6 - 8 weeks according to the RECIST criteria. The overall survival (OS) and time to progression (TTP) were defined as the time from administration of sorafenib to the death or the last follow up and were evaluated by Kaplan-Meier method.</p><p><b>RESULTS</b>There was no PR or CR, but 28 patients (56.0%) achieved stable disease. The median follow up time was 15 months with a median OS of 14 months and median TTP of 4 months. The common adverse events were dermal reaction (68.0%, 34/50), diarrhea (52.0%, 26/50), hypertension (4.0%, 2/50), hair loss (14.0%, 7/50), myelosuppression (16.0%, 8/50), and liver dysfunction (20.0%, 10/50). However, most of the drug-related adverse events were grade I-II and reversible. The patients with lower tumor burden and without distant metastasis had better prognosis.</p><p><b>CONCLUSION</b>Soafenib is effective for unresectable primary HCC with tolerable toxicity. Tumor stage is a predominant prognostic factor.</p>

Cryohepatectomy for liver cancer: preliminary evaluation of reducing postoperative recurrence / 中华外科杂志

<p><b>OBJECTIVE</b>To determine whether cryohepatectomy is potentially beneficial in reducing the recurrence and prolonging survival for hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>The study included 84 patients who underwent cryohepatectomy, cryosurgery with liquid nitrogen (-196 degrees C) followed by the resection of the frozen tumor by conventional technique, for HCC and were closely follow-up after surgery. Recurrence and survival rates were calculated by the life-table method.</p><p><b>RESULTS</b>The postoperative course of cryohepatectomy in all of the 84 patients was uneventful, there being no operative mortality or severe complications. The 1-, 3-, and 5-year survival rates after cryohepatectomy were 98.7%, 83.9% and 64.0%, respectively. The 1-, 3-, and 5-year recurrence rates after cryohepatectomy were 15.1%, 30.1% and 39.0%, respectively.</p><p><b>CONCLUSIONS</b>Cryohepatectomy for HCC is a safe procedure and may be potentially beneficial in reducing recurrence and prolonging survival. More time is needed to further define whether this procedure will improve long-term survival as compared with conventional resection.</p>

Effect of postoperative transcatheter arterial chemoembolization on hepatocellular carcinoma patients with residual tumor / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the effect of postoperative adjuvant transcatheter arterial chemoembolization (TACE) on hepatocellular carcinoma (HCC) patients with residual tumor.</p><p><b>METHODS</b>The patients were classified into intervention group (with adjuvant TACE) and control group (without adjuvant TACE) who were further stratified to those with high risk (patients with single tumor > 5 cm in diameter, or with multiple tumors, invasion to blood vessels), and low risk factors. Univariate analysis and Cox model were used to analyse prognostic factors.</p><p><b>RESULTS</b>In low risk patients with residual tumor, the 1-, 2-, 3-, 4-year survival rate was 97.2%, 78.0%, 66.5% and 66.5% in the intervention group, and 91.2%, 81.4%, 70.3% and 54.4% in the control group, respectively. There was no statistical difference between the two groups in survival (log-rank P = 0.7667). Comparing with the control group, the 1-, 2-, 3-, 4-year survival rate was 89.5%, 73.4%, 59.2% and 53.8% in the intervention group, and 70.5%, 61.9%, 46.8% and 46.8% in the control group, respectively. Postoperative adjuvant TACE significantly prolonged the survival in high risk patients with residual tumor (P = 0.0029). Cox model revealed that the benefit of adjuvant TACE was significantly increased by the high risk factors in HCC patients with residual tumor.</p><p><b>CONCLUSION</b>The beneficial effect of postoperative TACE was only observed in high risk patients with residual tumor but not in the low risk patients with residual tumor.</p>

Prospective randomized trial of RFA and chemotherapy for unresectable small hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the clinical safety and effect on local recurrence in unresectable small hepatocellular carcinoma treated by radiofrequency ablation (RFA) with and without chemotherapy through a prospective randomized trial.</p><p><b>METHODS</b>Thirty-eight unresectable small hepatocellular carcinoma patients with diameter </= 3 cm were selected, of which 27 patients have been followed up for 1 year. Through a prospective randomized trial, 12 patients were in the RFA group and 15 patients in the RFA combined with systemic chemotherapy group. RFA was given image-guided. The regimen of systemic chemotherapy: EADM 50 mg on day 1, 3; CDDP 40 mg on day 1, 3 and FUDR 500 mg on day 1, 2, 3. After RFA treatment, liver function, WBC count and complications were observed on day 1, 4, 7; CT scan was performed in 1, 6, 12 months. The safety and local recurrence were analyzed.</p><p><b>RESULTS</b>There was no local recurrence of the tumor in the two groups 1 month after RFA treatment. The 6- and 12-month local recurrence rates were significantly lower in the combined group than that in RFA group alone (P < 0.01). There were no severe complications in the two groups, and nor was there any significant difference in liver function and WBC count.</p><p><b>CONCLUSION</b>RFA combined with systemic chemotherapy is safe, and it can reduce the local recurrence of unresectable small hepatocellular carcinoma </= 3 cm in diameter.</p>