Chang Qing Zhang

Partial Hepatectomy With Wide Versus Narrow Resection Margin for Solitary Hepatocellular Carcinoma: A Prospective Randomized Trial

Objective:To compare the efficacy and safety of partial hepatectomy aiming grossly at a narrow (1 cm) and a wide (2 cm) resection margin in patients with macroscopically solitary hepatocellular carcinoma (HCC). Summary Background Data:For HCC treated with partial hepatectomy, the extent of the margin of liver resection remains controversial despite extensive studies. Methods:We conducted a prospective randomized trial in patients with solitary HCC. From January 1999 to February 2003, 169 patients with solitary HCC were stratified according to tumor size and randomized to undergo partial hepatectomy aiming grossly at either a narrow (1 cm) (n = 84) or a wide resection margin (2 cm) (n = 85). Analyses were done on an intention-to-treat basis. Results:The demographic and pathologic data were similar in the 2 groups. The mean ± SD for the final resection margin of the narrow and the wide margin groups were 0.7 ± 0.4 cm and 1.9 ± 0.6 cm, respectively. There was no significant difference in the morbidity and in-hospital mortality between the 2 groups of patients. The 1-, 2-, 3-, and 5-year overall survival rates for the narrow and the wide margin groups were 92.9%, 83.3%, 70.9%, and 49.1% and 96.5%, 91.8%, 86.9%, and 74.9%, respectively. The difference was significant (stratified log-rank test, P = 0.008). Multivariate analysis identified the presence of micrometastases and the treatment allocation were independent risk factors for tumor-related death. At the time of censor, 75 (44.4%) patients had developed tumor recurrence. All recurrences at the margins of liver resection were observed in the narrow margin group. Multiple tumor recurrence was also significantly higher in the narrow margin group (&khgr;2 test, P = 0.018). Survival after tumor recurrence was significantly better in the wide margin group than the narrow margin group (log-rank test, P = 0.017). Conclusion:For macroscopically solitary HCC, a resection margin aiming grossly at 2 cm efficaciously and safely decreased postoperative recurrence rate and improved survival outcomes when compared with a gross resection margin aiming at 1 cm, especially for HCC ≤2 cm.

Elevated plasma big ET-1 is associated with distant failure in patients with advanced-stage nasopharyngeal carcinoma†

Endothelin‐1 (ET‐1) is a potent vasoactive peptide and a hypoxia‐inducible angiogenic growth factor associated with the development and spread of solid tumors. The clinical significance of plasma big ET‐1 in patients with advanced‐stage nasopharyngeal carcinoma (NPC) is not known.

Therapeutic targeting of the endothelin a receptor in human nasopharyngeal carcinoma

The endothelin A receptor (ETAR) autocrine pathway is overexpressed in many malignancies, including nasopharyngeal carcinoma (NPC). In this tumor, ETAR expression is an independent determinant of survival and a robust independent predictor of distant metastasis. To evaluate whether ETAR represents a new target in NPC treatment, we tested the therapeutic role of ETAR in NPC. Cell proliferation was inhibited by the ETAR‐selective antagonist ABT‐627 in two ETAR‐positive NPC cells in a dose‐dependent manner. Proliferation of ETAR‐negative NPC cells was not decreased. ETAR blockade also resulted in sensitization to cisplatin and 5‐fluorouracil‐induced apoptosis. In nude mice, ABT‐627 inhibited the growth of NPC cell xenografts. Combined treatment of ABT‐627 with the cytotoxic drug cisplatin or 5‐fluorouracil produced additive antitumor effects. The antitumor activity of ABT‐627 was demonstrated finally on an experimental lung metastasis by a reduction in the number of tumors. These results support the rationale of combining ABT‐627 with current standard chemotherapy to further improve the therapeutic ratio in the treatment of NPC. (Cancer Sci 2006; 97: 1388–1395)

Elevated serum endostatin levels are associated with poor survival in patients with advanced-stage nasopharyngeal carcinoma.

AIMS To evaluate the prognostic value of serum endostatin levels in patients with advanced-stage nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS Between August 2003 and March 2005, 218 patients with advanced-stage NPC were enrolled in this study, including 70 patients in the training cohort and 148 in the validation cohort. The pre-treatment serum endostatin and vascular endothelial growth factor (VEGF) levels were measured using competitive enzyme immunoassays. For the normal control, serums samples from 20 healthy individuals were also collected. RESULTS Serum endostatin levels in the patients with advanced-stage NPC were significantly higher than those of controls, but VEGF levels were similar in the two groups. Univariate analysis revealed significant differences between the high and low endostatin level groups regarding 5 year overall survival (63.9% versus 90.5%; P = 0.003), progression-free survival (PFS) (50.2% versus 79.3%; P = 0.003) and distant metastasis-free survival (DMFS) (59.1% versus 85.3%; P = 0.01) in the training cohort. Using the same cut-off value generated from the training cohort, there were also significant unfavourable correlations between serum endostatin levels and overall survival (P = 0.001), PFS (P = 0.001) and DMFS (P = 0.002) in the second independent validation cohort. Multivariate analysis using the entire group (n = 218) revealed that the serum endostatin level was an independent unfavourable prognostic factor for overall survival (hazard ratio 4.8; 95% confidence interval 2.48-9.23; P < 0.0001), PFS (hazard ratio 3.44; 95% confidence interval 2.06-5.74; P < 0.0001) and DMFS (hazard ratio 3.65; 95% confidence interval 1.92-6.94; P < 0.0001) in patients with advanced-stage NPC. No associations were observed between the outcomes and the serum VEGF levels in patients with advanced-stage NPC. CONCLUSIONS High endostatin levels are associated with poor survival and this knowledge may improve the risk stratification of patients with advanced-stage NPC.

[Significance of cell-free Epstein-Barr virus DNA in monitoring prognosis of nasopharyngeal carcinoma].

ObjectiveIt has been reported that cell-free Epstein-Barr virus (EBV-DNA) in plasma was useful in diagnosing and monitoring nasopharyngeal carcinoma (NPC). The current study was designed to evaluate the significance of EBV-DNA in monitoring the prognosis of nasopharyngeal carcinoma and comparing its significance with that of plasma VCA/lgA and EA/lgA levels.MethodsE8V -DNA, VCA/lgA, and EA/lgA levels in plasma were determined in NPC patients with different prognosis after radiotherapy, including 30 distant metastatic patients, 22 local recurrence patients and 24 individuals with remission who had been followed-up for more than 2 years after treatment. EBV-DNA was determined using a real-time quantitative PCR system, and levels of VCA/lgA and EA/lgA were measured using standard immunofluorescence. In a cohort study, the indexes were determined after different radiation periods for the 20 new cases of nasopharyngeal carcinoma.ResultsThe median plasma EBV-DNA concentration was 135,100 copies/ ml (interquartile range: 5,525-1,003 750) in metastatic group, 20,500 copies/ ml (interquartile range: 0 -58,500) in the local recurrence group and 0 copies/ml (interquartile range: 0-0) in the continuous remission group (P< 0.05). The levels of VCA/lgA and EA/lgA showed no significant differences among the different groups. The high level of EBV-DNA concentration in the metastatic group was more than that in the local recurrence group. A level of 1,000,000 copies/ml of EBV DNA was an indication of distant metastasis of the NPC patients with a sensitivity of 27.3%. However, the sensitivity was 0 in the local recurrence group. For the 20 new patients, EBV -DNA concentration gradually decreased during the radiation period. Before radiation there were 32,050 copies/ml (interquartile range: 3,880-317,750), 0 copies/ml (interquartile range: 0-14 375) after a 40 Gy radiation dose and 0 copies/ml (interquartile range: 0-2940) after the radiation was finished (P< 0.05). However, the levels of VCA/lgA and EA/lgA showed no significant difference.ConclusionDetermination of plasma cell -free EBV -DNA level is more valuable than evaluation of VCA/lgA and EA/lgA for monitoring the prognosis of NPC patients.