Radiofrequency Ablation for Postoperative Recurrences of Intrahepatic Cholangiocarcinoma

Objective: Most recurrent intrahepatic cholangiocarcinoma (RICC) lost the opportunity of radical resection while most nonsurgical management failed to prolong patients’ survival. The efficacy and safety of radiofrequency ablation (RFA) as a local treatment for recurrent hepatocellular carcinoma have been confirmed by many clinical studies. The purpose of this study was to evaluate the efficacy, long-term survival and complications of RFA for RICC. Methods: A total of 12 patients with 19 RICCs after radical resection were included in this study. The tumors were 1.9–6.8 cm at the maximum diameter (median, 3.2±1.6 cm). All patients were treated with ultrasound guided RFA. There were two RFA approaches including percutaneous and open. Results: A total of 18 RFA treatment sessions were performed. Ablation was successful (evaluated by 1-month CT after the initial RFA procedure) in 18 (94.7%) of 19 tumors. By a median follow-up period of 29.9 months after RFA, 5 patients received repeated RFA because of intrahepatic lesion recurrence. The median local recurrence-free survival period and median event-free survival period after RFA were 21.0 months and 13.0 months, respectively. The median overall survival was 30 months, and the 1- and 3-year survival rates were 87.5% and 37.5%, respectively. The complication rate was 5.6% (1/18 sessions). The only one major complication was pleural effusion requiring thoracentesis. Conclusion: This study showed RFA may effectively and safely manage RICC with 3-year survival of 37.5%. It provides a treatment option for these RICC patients who lost chance for surgery.

EXPRESSION OF CDX2 IS ASSOCIATED WITH CLINICOPATHOLOGIC FEATURES AND PROGNOSIS OF GASTRIC CARCINOMA.

Objective： To explore the correlation between the Cdx2 expression and clinicopathologic features of patients with gastric carcinoma, and to evaluate the role of Cdx2 as a prognostic indicator of gastric carcinoma. Methods： The expression of Cdx2 was studied using immunohistochemistry of paraffin-embedded tumor specimens from 154 patients who underwent D2 resection for gastric adenocarcinoma from 1994 to 1998. Results： Cdx2 expression was detected in 35.1% （54 of 154） of gastric carcinoma cases. Expression of Cdx2 was significantly higher in intestinal-type carcinomas than in diffuse-type carcinomas, and in cases with TNM stage Ⅰ and Ⅱ than those with TNM stage Ⅲ and Ⅳ （P〈0.001 and P=-0.012, respectively）. There was a clear negative correlation between Cdx2 expression and lymph node metastasis （P=-0.049）. The patients with Cdx2-positive expression showed higher survival rate than those with Cdx2-negative expression （P〈0.0001）. Multivariate analysis revealed that the expression of Cdx2 was the independent prognostic indicator in this series （P〈0.001）. Conclusion： These data suggest that Cdx2 has significant value in predicting prognosis of gastric carcinoma.

EXPRESSION OF FLIP IN HUMAN COLON CARCINOMAS: A NEW MECHANISM OF IMMUNE EVASION

Objective： It has been proposed that Fas ligand （FasL） may play an important role in immune escape of tumors and FLIP is an important mediator of Fas/FasL pathway. In this study, the expression of FLIP was determined in human colon carcinoma cell lines and tissue to investigate the new mechanism of immune evasion of human colon carcinomas. Methods： RT-PCR and immunohistochemistry （IHC） were performed to investigate the expression of FLIP in human colon carcinoma cell lines SW480, LS174 and twenty human primary colon carcinoma specimens. Results： It was shown that SW480 cells, LS174 cells and primary colon carcinoma specimen constitutively expressed FLIP at the mRNA and protein level. The expression of FLIP was not found in the epithelial cells of normal colon mucosa. Conclusion： FLIP was expressed in human primary colon carcinoma specimens but not in the normal counterpart. It suggested that the expression of FLIP may occur during the malignant transformation from normal colon epithelial cells to colon carcinoma cells. Tumor cells might obtain the ability to resist the Fas-mediated apoptosis by expressing FLIP. The expression of FLIP might contribute to the formation of colon carcinomas.

STUDY ON THE EXPRESSION OF CYCLOOXYGENASE-2 IN HEPATOCELLULAR CARCINOMA CELL LINES AND ON THE GROWTH INHIBITION EFFECT OF NS-398

Objective： To investigate the expression of cyclooxygenase -2 （COX-2） in hepatocellular carcinoma cell lines and to explore the effect of NS-398, a selective inhibitor for COX-2, on HepG-2 cell line. Methods： lmmunohistochemistry and RT-PCR were used to investigate COX-2 expression in 6 HCC cell lines. MTT and Flowcytometry were used to evaluate the effect of the selective inhibitor of COX-2, NS-398, on HepG-2 cell lines. Results： All six HCC cell lines showed COX-2 expression at protein level. Five out of 6 cell lines showed COX-2 expression at mRNA level. NS-398 could suppress the growth of HepG-2 cell line, in a time and dose dependant manner. Conclusion： NS-398, a selective inhibitor of COX-2, showed inhibition effect on HepG-2 HCC cell line. The efficacy of inhibition was time and dose dependent, providing a new evidence for chemoprovention of hepatocellular carcinorma with COX-2 selective inhibitors.

EFFECT OF BODY MASS INDEX ON COLORECTAL CANCER

Objective: To evaluate the association between obesity and the risk of colorectal cancer. Methods: 331 patients with rectal cancer and 175 with colon cancer who accepted surgical operation at Beijing Cancer Hospital during 1995 and 2002 were enrolled. Data were collected by reviewing the pathology materials and hospital records. 258 healthy people who accepted health examination at Beijing Cancer Hospital during 2000 and 2002 were also enrolled as control. Data of height, weight and gender at the time of examination were also collected. Obesity was estimated by body mass index (BMI), computed as weight in kilograms divided by height in meters squared (kg/m2). The degree of obesity was compared between the two groups using BMI18.5, 24-27.9 and 28 (kg/m2) as the cut-off points for underweight, overweight and obesity. Associations with obesity were estimated by odds ratios (ORs) and 95% confidence intervals (CIs). All ORs were adjusted for age and sex. Results: Obesity was significantly prevalent in female patients with rectal cancer. All the patients with colon cancer showed lower level of BMI than control subjects. The ORs for rectal cancer rose with increasing BMI in women. Meanwhile, the ORs for colon cancer dropped with increasing BMI in both men and women. Obesity was an independent risk factor for rectal cancer, but not an independent risk factor for colon cancer. Conclusion: Rectal cancer and colon cancer may have different biological behavior. Obese women have relatively high risk for rectal cancer.

Prediction of recurrence risk in early breast cancer using human epidermal growth factor 2 and cyclin A2

Background Human epidermal growth factor 2 （HER2） is one of the most important prediction factors, but only 25%-30% of breast cancer patients HER2 are positive. It is unknown whether there are other molecular markers that could be used to predict prognosis and recurrence in HER2 negative patients.This study investigated correlations of cyclin A2 and HER2 levels with clinical outcomes in 281 patients with invasive breast cancer in order to identify whether cyclin A2 can serve as a prognostic factor in HER2 negative patients. Methods Immunohistochemical staining was used to detect cyclin A2 and HER2 expression in 281 patients. Cyclin A2 and HER2 gene amplifications were analyzed using gene analysis and RT-PCR in 12 patients. Risk and survival estimates were analyzed using Log-rank, Kaplan-Meier, and Cox regression analysis; cyclin A2 and HER2 consistency with survival were analyzed using Kappa analysis. Results Patients with higher cyclin A2 and HER2 expressions had significantly shorter disease-free survival periods （P=0.047 and P=-0.05, respectively）. Kappa analysis performed that cyclin A2 and HER2 showed a low Kappa index （kappa=0.37）, allowing us to conclude that cyclin A2 and HER2 detect different pathologies. Gene analysis and RT-PCR showed that cyclin A2 was upregulated in patients with early relapse; the average increase was 3.69-2.74 fold. Conclusions Cyclin A2 and HER2 are associated with proliferation and high recurrence, particularly when combined. Cyclin A2 is easily detected by nuclear staining and might be a useful biomarker for recurrence risk in HER2 negative patients.

IFN-γ REGULATES Fas/FasL EXPRESSION IN CHOLANGIO CARCINOMA CELLS

Objective: To study the regulation of Fas receptor (Fas)/Fas ligand (FasL) expression by IFN-γ in cholangiocarcinoma cell lines. Methods: We studied the expressions of Fas and FasL gene in the human cholangiocarcinoma cell line QBC939 by RT-PCR, Western blot, and immunohistochemistry and their apoptosis effects on human T cell line Jurkat cell. At the same time, we investigated the regulative effect of IFN-γ on them. Results: Fas, FasL mRNA and protein were expressed by cholangiocarcinoma cells. We also found IFN-γ could up-regulate the expressions of these two genes. However, IFN-γ could also down-regulate the ability of them to make Jurkat cells apoptotic. With the increasing of dosage and time, the effect was enhanced. Conclusion: IFN-γ could regulate the expression of Fas and FasL in cholangiocarcinoma cells, and might influence the ability of cholangiocarcinoma to regulate immune escape. This study provides new theoretical basis for immunological therapy of cholangiocarcinoma.

CARDIAC TOXICITY AFTER RADIATION THERAPY FOR 52 PATIENTS WITH MALIGNANT THYMIC TUMORS

Objective: To analyze the influencing factors for radiation-induced heart disease (RIHD) in a panel of cases with malignant thymic tumors treated by radiotherapy. Methods: 52 consecutive patients were treated by radiotherapy for malignant thymic tumor (14 at Masaoka stage II, 23 at stage III and 15 at stage IV). Treatment included radical (in 20), postoperative (in 14), preoperative (in 2) and palliative (in 16) radiotherapy. The conventional two-dimension (2D) radiation therapy was performed in forty-seven patients and three-dimension (3D) conformal radiation therapy has been used in 5 patients since October 2000. The total tumor dose ranged from 10 Gy to 84.5 Gy (median of 55 Gy). Chemotherapy was given in twenty-five patients before or after radiotherapy. The results of following-up could be obtained from the database and updated where appropriated. The dose volume histogram (DVH) of heart in radiotherapy for all patients was analyzed for the effective volume dose of heart. Result: The median following-up was 14 months (ranged from 0.6 to 111.3 months) in the study. RIHD was observed in seven patients. Cardiac toxicity of these seven patients were evaluated as SOMA grade 1-3. The median two-third effective volume dose of heart was 47.2 Gy (ranged from 8.3 Gy to 70.1 Gy) for conventional 2D radiotherapy, which correlated with thymic tumor dose (P<0.0001). The median two-third effective volume dose of heart was 35.3 Gy (ranged from 13 Gy to 38.7 Gy) for 3D conformal radiotherapy. The effective volume doses of heart were decreased by using 3D conformal radiotherapy (P=0.048). A significant association between cardiac toxicity and effective volume dose of heart was found in this study (P<0.0001). Cardiac toxicity accounted for 10.4% and 4.1% of patients receiving and not receiving adjuvant chemotherapy, respectively, and occurred earlier in radiochemotherapy group (P=0.0528). Multivariate analysis suggested that cardiac toxicity was significantly influenced by the effective volume dose of heart and chemotherapy. Conclusion: the results indicate that decreasing the effective volume dose of heart and carefully using chemotherapy drugs that have significant cardiotoxicity may reduce the probability of radiation-induced heart disease.