Xiao Jun Lin

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 With or Without Transcatheter Arterial Chemoembolization in the Treatment of Hepatocellular Carcinoma: A Prospective Randomized Trial

PURPOSE To compare radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). PATIENTS AND METHODS A randomized controlled trial was conducted on 189 patients with HCC less than 7 cm at a single tertiary referral center between October 2006 and June 2009. Patients were randomly asssigned to receive TACE combined with RFA (TACE-RFA; n = 94) or RFA alone (n = 95). The primary end point was overall survival. The secondary end point was recurrence-free survival, and the tertiary end point was adverse effects. RESULTS At a follow-up of 7 to 62 months, 34 patients in the TACE-RFA group and 48 patients in the RFA group had died. Thirty-three patients and 52 patients had developed recurrence in the TACE-RFA group and RFA group, respectively. The 1-, 3-, and 4-year overall survivals for the TACE-RFA group and the RFA group were 92.6%, 66.6%, and 61.8% and 85.3%, 59%, and 45.0%, respectively. The corresponding recurrence-free survivals were 79.4%, 60.6%, and 54.8% and 66.7%, 44.2%, and 38.9%, respectively. Patients in the TACE-RFA group had better overall survival and recurrence-free survival than patients in the RFA group (hazard ratio, 0.525; 95% CI, 0.335 to 0.822; P = .002; hazard ratio, 0.575; 95% CI, 0.374 to 0.897; P = .009, respectively). There were no treatment-related deaths. On logistic regression analyses, treatment allocation, tumor size, and tumor number were significant prognostic factors for overall survival, whereas treatment allocation and tumor number were significant prognostic factors for recurrence-free survival. CONCLUSION TACE-RFA was superior to RFA alone in improving survival for patients with HCC less than 7 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 transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with portal vein tumor thrombus

The long‐term survival outcomes of hepatic resection (HR) compared with transcatheter arterial chemoembolization (TACE) for resectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) are unclear.

Primary carcinosarcoma of the liver: Clinicopathologic features of 5 cases and a review of the literature

Carcinosarcoma of the liver is very rare worldwide. The terminology and pathogenesis of hepatic carcinosarcoma remain controversial issues. In this article, we studied the clinicopathologic features of 5 cases of hepatic carcinosarcomas (matching the World Health Organization definition), analyzed the clinical data, histologic and immunohistochemical (IHC) results, and discussed the terminology, pathologic differential diagnoses, pathogenesis, and prognosis. The patients were 40 to 68 years old, and included 4 males and 1 female. All patients were Hepatitis B surface antigen positive with para-tumorous cirrhosis. The largest dimensions of the neoplasms ranged from 6.0 to 14.0 cm. Satellite nodules, portal vein tumor thrombi, direct invasion into local tissues (right diaphragm, right adrenal gland, and gastric wall) as well as metastatic foci in lungs and abdominal lymph nodes were identified. Pathologically, the neoplasms consisted of carcinomatous and sarcomatous components. The carcinomatous components were exclusively conventional hepatocellular carcinomas in all 5 cases, whereas the sarcomatous components exhibited complex features. Confirmed by IHC studies, the sarcomatous elements in different cases included rhabdomyosarcomas, malignant fibrous histiocytomas, fibrosarcoma, and poorly differentiated spindle cells without distinctive differentiation. Furthermore, the sarcomatous elements in these 5 neoplasms stained negative for all the epithelial markers we applied for IHC staining, which support the pathologic diagnosis of carcinosarcoma rather than sarcomatoid carcinoma. The presence of transitional zones between carcinomatous and sarcomatous components may support the transformation theory. Four patients with palliative hepatectomy died within 6 months, whereas 1 patient is still alive 21 months after radical resection. The poor prognosis of hepatic carcinosarcoma may be due to their highly invasive and metastatic features. Radical resection of early stage hepatic carcinosarcoma may contribute to a relatively optimistic prognosis.

Roles Played by Chemolipiodolization and Embolization in Chemoembolization for Hepatocellular Carcinoma: Single-Blind, Randomized Trial

BACKGROUND The aim of our study was to compare the efficacy and safety of: 1) transarterial chemolipiodolization with gelatin sponge embolization vs chemolipiodolization without embolization, and 2) chemolipiodolization with triple chemotherapeutic agents vs epirubicin alone. METHODS A single-blind, three parallel arm, randomized trial was conducted at three clinical centers with patients with biopsy-confirmed unresectable hepatocellular carcinoma. Arm 1 received triple-drug chemolipiodolization and sponge embolization, whereas Arm 2 received triple-drug chemolipiodolization only. Patients in arm 3 were treated with single-drug chemolipiodolization and sponge embolization. We compared overall survival and time to progression. Event-time distributions were estimated by the Kaplan-Meier method. All statistical tests were two-sided. RESULTS From July 2007 to November 2009, 365 patients (Arm 1: n = 122; Arm 2: n = 121; Arm 3: n = 122) were recruited. The median tumor size was 10.9cm (range = 7-22cm), and 34.5% had macrovascular invasion. The median survivals and time to progression in Arm 1, Arm 2, and Arm 3 were 10.5 and 3.6 months, 10.1 and 3.1 months, and 5.9 and 3.1 months, respectively. Survival was statistically significantly better in Arm 1 than in Arm 3 (P < .001), whereas there was no statistically significant difference between Arm 1 and Arm 2 (P = .20). Objective response rates were 45.9%, 29.7%, and 18.9% for Arm 1, Arm 2, and Arm 3, respectively. CONCLUSIONS Chemolipiodolization played an important role in transarterial chemoembolization, and the choice of chemotherapy regimen may largely affect survival outcomes. However, the removal of embolization from chemoembolization might not statistically significantly decrease survival.

Radiofrequency ablation versus open hepatic resection for elderly patients (> 65 years) with very early or early hepatocellular carcinoma.

This study retrospectively compared the safety and efficacy of percutaneous radiofrequency ablation (RFA) with open hepatic resection (HR) in elderly patients (age > 65 years) with very early or early hepatocellular carcinoma (HCC).

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.