Min Shan Chen

A Prospective Randomized Trial Comparing Percutaneous Local Ablative Therapy and Partial Hepatectomy for Small Hepatocellular Carcinoma

Objective:To compare the results of percutaneous local ablative therapy (PLAT) with surgical resection in the treatment of solitary and small hepatocellular carcinoma (HCC). Summary Background Data:PLAT is effective in small HCC. Whether it is as effective as surgical resection in the long-term survivals remains unknown. Methods:We conducted a prospective randomized trial on 180 patients with a solitary HCC ≦5 cm to receive either PLAT or surgical resection. The patients were regularly followed up after treatment with physical examination, blood, and radiologic tests. Results:Of the 90 patients who were randomized to PLAT, only 71 received PLAT because 19 withdrew their consent. Of the 90 patients who were randomized to surgical resection, a single Couinaud liver segment resection was carried out in 69 patients, 2 segments in 16 patients, and 3 or more segments in 3 patients. Ethanol injection was given during open surgery in 2 patients. Only 1 patient died after surgical resection within the same hospital admission. Posttreatment complications were more often and severe after surgery than PLAT. The 1-, 2-, 3-, and 4-year overall survival rates after PLAT and surgery were 95.8%, 82.1%, 71.4%, 67.9% and 93.3%, 82.3%, 73.4%, 64.0%, respectively. The corresponding disease-free survival rates were 85.9%, 69.3%, 64.1%, 46.4% and 86.6%, 76.8%, 69%, 51.6%, respectively. Statistically, there was no difference between these 2 treatments. Conclusion:PLAT was as effective as surgical resection in the treatment of solitary and small HCC. PLAT had the advantage over surgical resection in being less invasive.

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.

Radiofrequency Ablation versus Hepatic Resection for the Treatment of Hepatocellular Carcinomas 2 cm or Smaller: A Retrospective Comparative Study

PURPOSE To compare retrospectively the effects of percutaneous radiofrequency (RF) ablation with those of hepatic resection in the treatment of hepatocellular carcinoma (HCC) measuring 2 cm or smaller. MATERIALS AND METHODS This study was approved by the institutional ethics committee, and all patients provided written informed consent before treatment. From December 2003 to December 2008, 145 patients with a resectable HCC measuring 2 cm or smaller were studied. Sixty-six patients had a central HCC (located at least 3 cm from the liver capsule). As an initial treatment, 71 patients were treated with percutaneous RF ablation and 74 with surgical resection. Of the patients with central HCC, 37 underwent percutaneous RF ablation and 29 underwent surgical resection. Survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. The relative prognostic significance of the variables for predicting overall survival rates was assessed with multivariate Cox proportional hazards regression analysis. Complications were observed clinically when patients were admitted and assessed by telephone interview after patients were discharged. RESULTS One death was considered to be related to treatment after surgical resection. Major complications occurred significantly more often in the surgical resection group (38 of 74 patients) than in the RF ablation group (14 of 71 patients) (P = .009). The 1-, 3-, and 5-year overall survival rates were 98.5%, 87.7%, and 71.9%, respectively, with RF ablation and 90.5%, 70.9%, and 62.1% with surgical resection (P = .048). The corresponding recurrence-free survival rates were 76.4%, 65.2%, and 59.8% with RF ablation and 75.6%, 56.1%, and 51.3% with surgical resection (P = .548). At subgroup analysis of patients with central HCC, 1-, 3-, and 5-year overall survival rates were 96.6%, 93.0%, and 79.9% with RF ablation and 92.0%, 71.6%, and 61.5% with surgical resection (P = .020). The corresponding recurrence-free survival rates were 86.5%, 74.0%, and 67.0% with RF ablation and 68.0%, 40.0%, and 40.0% with surgical resection (P = .033). For patients with peripheral HCC, 1-, 3-, and 5-year overall survival rates were 97.3%, 83.3%, and 65.1% with RF ablation and 87.8%, 68.4%, and 62.9% with surgical resection (P = .464). The corresponding recurrence-free survival rates were 68.7%, 59.2%, and 54.9% with RF ablation and 82.9%, 66.6%, and 52.9% with surgical resection (P = .351). CONCLUSION The efficacy and safety of percutaneous RF ablation were better than those of surgical resection in patients with HCC measuring 2 cm or smaller, especially those with central HCC.

Recurrent Hepatocellular Carcinoma Treated with Sequential Transcatheter Arterial Chemoembolization and RF Ablation versus RF Ablation Alone: A Prospective Randomized Trial

PURPOSE To compare prospectively the effects of radiofrequency (RF) ablation after transcatheter arterial chemoembolization (TACE) with those of RF ablation alone in the treatment of recurrent hepatocellular carcinoma (HCC). MATERIALS AND METHODS This study was approved by the institutional ethics committee, and all patients gave written informed consent. From January 2002 to December 2006, 139 patients with recurrent HCC measuring 5 cm in diameter or smaller were randomized to receive either sequential TACE and RF ablation (sequential treatment group, n=69) or RF ablation alone (RF ablation group, n=70). The survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. Bonferroni correction was applied when multiple comparisons were performed. P<.0083 (.05÷6) was considered indicative of a statistically significant difference. RESULTS The 1-, 3-, and 5-year overall survival rates were 94%, 69%, and 46%, respectively, for the sequential treatment group and 82%, 47%, and 36% for the RF ablation group (P=.037). The corresponding recurrence-free survival rates were 80%, 45%, and 40% for the sequential treatment group and 64%, 18%, and 18% for the ablation group (P=.005). At subgroup analyses, the overall survival for the sequential treatment group was better than that for the RF ablation group for patients with tumor recurrence 1 year or less after initial treatment (P=.004) and those with tumors measuring 3.1-5.0 cm (P=.002) but not for those with tumor recurrence more than 1 year after initial treatment (P=.421) and those with tumors 3.0 cm or smaller (P=.478). The recurrence-free survival in the sequential treatment group was better than that in the RF ablation group for patients with tumors measuring 3.1-5.0 cm (P<.001) but not for those with tumors 3.0 cm or smaller (P=.204). For recurrence-free survival, there was no significant difference between the two groups for patients with tumor recurrence 1 year or less or more than 1 year after initial treatment (P=.020 and P=.111, respectively). Logistic regression analysis showed that treatment allocation and the interval between initial treatment and tumor recurrence were significant prognostic factors for overall survival, whereas the interval between initial treatment and tumor recurrence, treatment allocation, and tumor size were significant prognostic factors for recurrence-free survival. CONCLUSION The efficacy of sequential TACE-RF ablation is better than that of RF ablation alone for recurrent HCC.

Hepatic resection versus transarterial lipiodol chemoembolization as the initial treatment for large, multiple, and resectable hepatocellular carcinomas: a prospective nonrandomized analysis.

PURPOSE To compare the survival outcomes between hepatic resection and transarterial lipiodol chemoembolization (TACE) used as the initial treatment in patients with large (≥5 cm), multiple, and resectable hepatocellular carcinomas. MATERIALS AND METHODS This study had local ethical committee approval; all patients gave written informed consent. Between January 2004 and December 2006, 168 consecutive patients were prospectively studied. As an initial treatment, 85 patients underwent hepatic resection and 83 underwent TACE. Of the 29 of 83 patients in whom there was a good response to TACE, 13 underwent subsequent hepatic resection. The remaining 16 patients, who refused hepatic resection, underwent TACE and local ablation. Repeated TACE was performed in patients with stable disease or progressive disease after initial TACE. The differences in survival between groups and subgroups were calculated with the Kaplan-Meier method. Univariate and multivariate analyses were performed to clarify the prognostic factors for survival. RESULTS The 1-, 3-, and 5-year overall survival rates for the initial hepatic resection group and the initial TACE group were 70.6%, 35.3%, 23.9% and 67.2%, 26.0%, 18.9%, respectively (P = .26). Complication rates were significantly higher in the initial hepatic resection group than in the initial TACE group (P < .01). The 1-, 3-, and 5-year overall survival rates in patients who underwent initial TACE and subsequent hepatic resection were 92.3%, 67.3%, and 50.5%, respectively, which were significantly higher than rates in patients treated with initial hepatic resection (P = .04) but were not significantly higher than in patients who responded well to TACE but refused hepatic resection (P = .07). Tumor size was the independent risk factor for survival. CONCLUSION TACE might be a better initial treatment in patients with large, multiple, and resectable hepatocellular carcinomas; hepatic resection should be recommended to patients who respond well to TACE.

Antitumour activity of Lycium chinensis polysaccharides in liver cancer rats

In the present study, polysaccharides were extracted from the Lycium chinensis (LCP). Rats were divided into four groups. Two groups (Groups A) were maintained on the basal diet, whereas the remaining three groups (Groups B, C and D) had free access to the basal diet and were orally fed with LCP at 200 mg/kg b.w. for Group B, 400 mg/kg b.w. for Group C and 600 mg/kg b.w. for Group D, respectively. Following 4 weeks of this dietary regimen, hepatocarcinogenesis was initiated in all animals by a single intraperitoneal DENA (Sigma-Aldrich, St. Louis, MO, USA) injection at a dose of 200 mg/kg body weight (mixed with peanut oil). Results still showed that L. chinensis polysaccharides (LCP) increased spleen, thymus indexs, antioxidant enzymes activities and decreased oxidative injury. In addition, LCP still significantly affect VEGF and Cyclin D1 proteins expression in liver cancer rats. It can be concluded that LCP exhibited remarkable protective effects against diethylnitrosamine (DEN)-induced oxidative hepatic injury in liver cancer rats.