Subdivision of M category for nasopharyngeal carcinoma with synchronous metastasis: time to expand the M categorization system.

INTRODUCTION: The current metastatic category (M) of nasopharyngeal carcinoma (NPC) is a "catch-all" classification, covering a heterogeneous group of tumors ranging from potentially curable to incurable. The aim of this study was to design an M categorization system that could be applied in planning the treatment of NPC with synchronous metastasis. METHODS: A total of 505 NPC patients diagnosed with synchronous metastasis at Sun Yat-sen University Cancer Center between 2000 and 2009 were involved. The associations of clinical variables, metastatic features, and a proposed M categorization system with overall survival (OS) were determined by using Cox regression model. RESULTS: Multivariate analysis showed that Union for International Cancer Control (UICC) N category (N1-3/N0), number of metastatic lesions (multiple/single), liver involvement (yes/no), radiotherapy to primary tumor (yes/no), and cycles of chemotherapy (>4/≤4) were independent prognostic factors for OS. We defined the following subcategories based on liver involvement and the number of metastatic lesions: M1a, single lesion confined to an isolated organ or location except the liver; M1b, single lesion in the liver and/or multiple lesions in any organs or locations except the liver; and M1c, multiple lesions in the liver. Of the 505 cases, 74 (14.7%) were classified as M1a, 296 (58.6%) as M1b, 134 (26.5%) as M1c, and 1 was not specified. The three M1 subcategories showed significant difference in OS [M1b vs. M1a, hazard ratio (HR) = 1.69, 95% confidence interval (CI) = 1.16-2.48, P = 0.007; M1c vs. M1a, HR = 2.64, 95% CI = 1.75-3.98, P < 0.001]. CONCLUSIONS: We developed an M categorization system based on the independent factors related to the prognosis of patients with metastatic NPC. This system may be helpful to further optimize individualized care for NPC patients.

[Evaluation of the prognostic significance of refinement and stratification of distant metastasis status in 1016 cases of nasopharyngeal carcinoma].

OBJECTIVE: To investigate the prognostic factors for nasopharyngeal carcinoma (NPC) with different metastatic status, and to improve the NPC management by multi-level refinement and stratification of M1 stage distant metastases. METHODS: Clinicopathological data of 1016 NPC patients with distant metastases were retrospectively reviewed. The M1 stage distant metastases were subdivided into synchronous or metachronous metastases, metastatic sites (lung, bone, liver), number of metastatic organs (solitary, multiple) and number of metastases (solitary, multiple) subgroups to analyze the prognosis and survival of the patients. RESULTS: The most frequently involved metastatic sites were bone (542, 53.3%), lung (420, 41.3%) and liver (302, 29.7%). There were solitary metastatic lesions in 164 patients (16.2%), synchronous metastases in 376 cases and metachronous metastases in 640 cases. The median overall survival of the whole group of 1016 NPC patients was 30.8 months since the time of diagnosis of metastasis. For the 376 patients in the synchronous metastasis group, the median survival was 23.3 months and the 1-, 3- and 5-year overall survival rates were 74.2%, 27.6% and 18.5%, respectively. For the 640 patients in the metachronous metastases group, the median survival was 36.7 months, and the 1-, 3- and 5-year overall survival rates were 88.1%, 49.6% and 28.6%, respectively, with a significant difference between the two groups (all P < 0.001). Cox multivariate analysis indicated that the number of metastatic lesions, different metastatic sites and N stage at initial diagnosis were independent prognostic factors for patients with metachronous metastases (P < 0.05). CONCLUSIONS: A theory of detailed multi-level metastasis (M1) stratification aiming at different distant metastasis status for nasopharyngeal carcinoma is proposed. To take appropriate individualized treatment scheme according to the prognosis and expected survival should be helpful to improving the diagnosis and treatment of nasopharyngeal cancer.

Efficacy of minimally invasive therapies on unresectable pancreatic cancer.

For patients with unresectable pancreatic cancer, current chemotherapies have negligible survival benefits. Thus, developing effective minimally invasive therapies is currently underway. This study was conducted to evaluate the efficacy of transarterial chemoembolization plus radiofrequency ablation and/or 125I radioactive seed implantation on unresectable pancreatic cancer. We analyzed the outcome of 71 patients with unresectable pancreatic carcinoma who underwent chemoembolization plus radiofrequency ablation and/or radioactive seed implantation. Of the 71 patients, the median survival was 11 months, and the 1-, 2-, and 3-year overall survival rates were 32.4%, 9.9%, and 6.6%, respectively. Patients who had no metastasis, who had oligonodular liver metastases (≤3 lesions), and who had multinodular liver metastases (>3 lesions) had median survival of 12, 18, and 8 months, respectively, and 1-year overall survival rates of 50.0%, 68.8%, and 5.7%, respectively. Although the survival of patients without liver metastases was worse than that of patients with oligonodular liver metastasis, the result was not significant (P = 0.239). In contrast, the metastasis-negative patients had significantly better survival than did patients with multinodular liver metastases (P < 0.001). Patients with oligonodular liver lesions had a significant longer median survival than did patients with multinodular lesions (P < 0.001). In conclusion, combined minimally invasive therapies had good efficacy on unresectable pancreatic cancer and resulted in a good control of liver metastases. In addition, the number of liver metastases was a significant factor in predicting prognosis and response to treatment.

[Clinicopathological features and multivariate analysis of prognostic factors for patients with gastroenteropancreatic neuroendocrine tumors].

OBJECTIVE: To analyze the clinicopathologic characteristics of gastroenteropancreatic neuroendocrine neoplasm(GEP-NET) and explore the prognostic factors for patients with GEP-NET. METHODS: Retrospectively reviews were conducted for the charts of 68 patients diagnosed pathologically with GEP-NET and treated at Sichuan Cancer Hospital during January 2001 to June 2012. The information of prognostic factors was retrieved and analyzed. Kaplan-Meier method was used to estimate survival rates and plot patient survival curves of patients at different levels of predictive factors. The association between clinicopathologic characteristic and prognosis in GEP-NET patients was assessed with Log-rank test. Meanwhile Cox proportional hazard model was used to select independent risk factors of patient survival. RESULTS: Stomach (20/68,29.41%) and cardia (16/68,23.53%) were mostly involved. Frequent tumor sites for males were stomach and cardia (34/52,65.38%) while the most common site was intestinal canal for female (12/16) . Ages of disease onset were different significantly among patient groups of different sites (P = 0.023). The average age of intestinal NET was the highest while gastric NET had the lowest. During a median follow-up duration of 49 (3-120)months, there were 37 deaths (54.41%), including 30 from postoperative relapses. Postoperative survival time ranged from 4-115 months. The mean survival periods were (46 ± 7) months respectively. The 1, 3, and 5-year survival rates were 65.1%, 41.5% and 28.7% respectively. Univariate analyses showed that the risk factors of survival time were patient age over 60 years, tumor size > 2 cm, T2-4 stage of tumor, vascular invasion, lymph node metastasis, distant metastasis, positive surgical margin and pathological grades of neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC). Multivariate analysis indicated independent risk factors were tumor size > 2 cm and pathological grades of NEC and MANEC. CONCLUSIONS: GEP-NET may occur at multiple sites of digestive system and lack specific clinical manifestations. Tumor size, distant metastasis and pathological grades were independent prognostic factors for GEP-NET patients.

[Value of CIK in the treatment of TACE combined with RFA for HCC in long-term survival and prognostic analysis].

OBJECTIVE: To assess the long-term efficacy and investigate the prognostic factors of cytokine-induced killer (CIK) combined with the sequential transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) on hepatocellular carcinoma (HCC). METHOD: A total of 95 HCC patients with the informed consents received TACE combined with RFA, 48 cases of which accepted the CIK via intravenous drop infusion for more than 6 times (study group) while the other 47 cases were enrolled in control group. The following-up duration was more than 3 years. Primary endpoint was the overall survival (OS) and the secondary endpoint was the disease-free survival (DFS). RESULTS: 76 patients in all (38 in study group, 38 in control group) complied with the study and follow-up (44 months in median, 10-88 months). No mortality and serve complications were observed in both groups. The ratio for patients with DFS over 1-year, 3-year and 5-year were 79%, 26% and 16% (28 months in median and 32.3 months in mean) while 71%, 21% and 8% (22 months in median and 23.1 months in mean) for the control group. There was significant difference between the two groups (P=0.001). For the OS, the ratio for 1-year, 3-year and 5-year in the study group were 92%, 53% and 26% (38 months in median and 42.5 in mean) and 89%, 42% and 24% (35 months in median and 37 in mean). No significant difference was observed in both groups. ECOG performance status, Hepatitis B virus infection and treatment were the prognostic factors for DFS while ECOG performance status was the only prognosis for OS. CONCLUSION: CIK infusion basing on the TACE combined with RFA can control the recurrence of HCC, decrease the times of TACE or RFA.

[Comparison of safety and efficacy for transcatheter arterial chemoembolization alone and plus radiofrequency ablation in the treatment of single branch portal vein tumor thrombus of hepatocellular carcinoma and their prognosis factors].

OBJECTIVE: To compare the transcatheter arterial chemoembolization (TACE) alone or plus radiofrequency ablation (RFA) in the treatment of single branch portal vein tumor thrombus(PVTT)in patients with hepatocellular carcinoma (HCC) so as to evaluate the safety, control rate, prognostic factors and overall survival. METHODS: From January 2004 to December 2007, 50 HCC patients (< 5 cm in diameter and 3 parenchymal lesions) with concurrent PVTT were enrolled and treated by TACE alone or TACE plus RFA randomly (TACE, n = 25; TACE-RFA, n = 25). In TACE group, the intra-hepatic lesions received TACE sequentially with RFA; in TACE-RFA group, PVTT and intra-hepatic lesions were treated with TACE sequentially with RFA separately. Strict follow-up was conducted by computed tomography and alpha-fetoprotein (AFP) assay. The survival time was analyzed by the Kaplan-Meier method and Cox regression analysis was performed to evaluate the prognostic factors. RESULTS: Of all 50 HCC patients with single branch PVTT with TACE or RFA, 47 patients (TACE, n = 24; TACE-RFA, n = 23) received all the scheduled procedures and completed the follow-up. Two patients (8.3%) in TACE group had liver dysfunction versus none in TACE-RFA group, 2 patients (8.7%) developed bile duct injury in TACE-RFA group related with the RFA procedure. The OR (overall response) for PVTT was 54.2% (complete response (CR) 8.3%, partial response (PR) 45.8%) in TACE group while 87.0% (CR 60.9%, PR 26.1%) in TACE-RFA group during the follow-up. From the definite diagnosis of HCC, the median survival was 8 months. And the 1-, 2- & 3-year survival rates were 33.3%, 12.5%, 8.3% in TACE group. And 26 months, 65.2%, 47.8%, 30.4% in TACE-RFA group respectively. The difference between two groups was significant. From the definite diagnosis of PVTT, the respective data were 7 months, 12.5% and 4.2%, 0 in TACE group versus 22 months, 52.2%, 34.8%, and 8.7% in TACE-RFA group with a significant P value. In multivariate analysis, only therapy (TACE or TACE-RFA) showed a protective value (hazard rate 0.430 vs 0.345, P < 0.05). Survival was not correlated with age, intra-hepatic tumor status, liver functions and AFP level for all patients. CONCLUSION: RFA is both safe and efficacious to prolong survival in the treatment of single branch PVTT plus TACE in selected HCC patients. It may provide rationales for further studies of evaluating the outcome of RFA plus other therapies in the treatment of HCC with single branch PVTT.

Percutaneous radiofrequency ablation approach through the spleen: initial case report for pancreatic tail gastrinoma.

Gastrinoma has a low incidence, and the pancreas-originated gastrinoma is rare. Pancreatic gastrinoma patients with liver metastases have poor prognosis and short survival. Local treatment to reduce the tumor burden helps to improve symptoms and slows down tumor progression for patients with unresectable tumors. We report a case of pancreatic tail gastrinoma with unresectable liver metastases. The patient received a comprehensive minimally invasive interventional treatment, that is, chemoembolization and radiofrequency ablation for liver metastases, and percutaneous transplenic radiofrequency ablation combined with radioactive 125I seed implantation for pancreatic tail gastrinoma. The patient was followed up for more than 20 months, and showed no clear evidence of tumor recurrence. We explored the safety and feasibility of percutaneous transplenic radiofrequency ablation for unresectable pancreatic tail gastrinoma. This transplenic approach allow more indications for minimally invasive therapy and provides a new treatment option not only for patients with unresectable pancreatic tail tumor but also for patients refusing surgery.

Serum alpha-fetoprotein measurement in predicting clinical outcome related to autologous cytokine-induced killer cells in patients with hepatocellular carcinoma undergone minimally invasive therapy.

BACKGROUND AND OBJECTIVE: In patients with hepatocellular carcinoma (HCC) receiving potentially curative minimally invasive therapy, autologous cytokine-induced killer (CIK) cells were used to reduce recurrence. In this study we observed the changes in serum alpha-fetoprotein (AFP) after the treatment with CIK cells to explore if AFP could serve as a marker for predicting immunotherapeutic clinical outcome. METHODS: A total of 122 patients with HCC and elevated AFP (>25 ng/mL) received a curative treatment of transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA) at the Sun Yat-sen University Cancer Center. Of these patients, 83 patients without residual tumor or extrahepatic metastasis and with AFP level less than 1.5 times the normal range (AFP<37.5 ng/mL) were randomly assigned to the study group (n=42) and the control group (n=41). In the study group, CIK cells were transfused intravenously or via common hepatic arteries every week for at least 4 times, and the T-lymphocyte subset data before and after CIK cell infusions was examined by flow cytometry. All the two groups of patients were screened by tomography every 2 months to observe tumor recurrence. Serum AFP was collected at baseline and at different time points after treatment in parallel with radiologic response and clinical outcome. RESULTS: Two patients in the control group were lost to follow-up after treatment. After CIK cell infusions, the downtrend of the AFP level was observed in the study group and not in the control group. There was a significant difference in the level of AFP between different time points after CIK infusions in both groups. The 1-year recurrence rate was 7.14% for the study group and 23.1% for the control group (P=0.044). In subgroup analysis, for patients with a slightly high level of AFP (25 ng/mL

[Comparative analysis of TACE alone or plus RFA in the treatment of 167 cases of intermediate and advanced staged primary hepatocellular carcinoma].

OBJECTIVE: To evaluate the clinical efficacy and survival rate of transarterial chemoembolization (TACE) alone or plus radiofrequency ablation (RFA) in patients with intermediate or advanced stage primary hepatocellular carcinoma (HCC). METHODS: In this retrospective study, 467 cases received RFA or TACE plus RFA. Among them, 167 cases with strict clinical procedure (TACE alone or plus RFA) and complete follow-up data were included. Eighty-seven cases received TACE and 80 cases had TACE plus RFA between January 2000 and December 2006. Hierarchical analyses were performed using log-rank tests and survival curve was estimated by Kaplan-Meier method. RESULTS: A total of 167 patients received TACE alone or plus RFA for a follow-up period of 1 to 89 months. In the TACE alone group, the time-to-progression (TTP) was an average of 3.6 months. The median survival was 13 months, one-year survival rate 52.9%, three-year survival rate 11.5% and five-year survival rate 4.6%. In the TACE plus RFA group, the TTP time was an average of 10.8 months. The median survival time was 30 months, one-year survival rate 85.0%, three-year survival rate 45.0% and five-year survival rate 11.3%. In the TACE alone group, the median survival of intermediate stage HCC was 14 months, one-year survival rate 62.2%, three-year survival rate 13.3% and five-year survival rate 4.4%; In the TACE plus RFA group, the median survival of intermediate stage HCC was 14 months, one-year survival rate 90.1%, three-year survival rate 52.9% and five-year survival rate 13.7%. All differences of two groups has statistical significance (P < 0.05). In intermediate stage HCC, the median survival of TACE alone group was 14 months, one-year survival rate 62.2%, three-year survival rate 13.3%, five-year survival rate 4.4% versus 32 months, 90.1%, 52.9%, 13.7% in the TACE plus RFA group respectively. For the advanced stage HCC, the median survival time was 12 months, one-year survival rate 35%, three-year survival rate 7.1% and five-year survival rate 0 in the TACE alone group versus 28 months, 62.1%, 24.1% and 6.9% in the TACE plus RFA group (P = 0.00). There was significantly statistic difference between both groups in intermediate and advanced staging HCC. Among them, 60/485 (12.4%) patients required a therapy of post-TACE hepatic dysfunctions versus 13/168 (7.7%) in the TACE plus RFA group (P = 0.004, ANOVA method). CONCLUSION: The regimen of TACE plus RFA has the advantages of tumor control, liver function protection and survival extending in the treatment of HCC than TACE alone in intermediate or advanced stage HCC.

A Prognostic Score for Nasopharyngeal Carcinoma with Bone Metastasis: Development and Validation from Multicenter.

Background: To establish a prognostic score based on clinical routine factors to stratify nasopharyngeal carcinoma patients with bone metastasis into risk groups with different survival rates. Materials and Methods: Total 276 patients from multicenter were retrospectively analyzed. Kaplan-Meier method and Cox regression were used to confirm independent risk factors, which were checked for internal validity by bootstrapping method. The prognostic score, deriving from the corresponding regression coefficients in Cox model, classified patients into low and high risk groups. Finally, two independent cohorts were used for external validation. Results: In development cohort, six risk factors were identified: age>46 year-old (point=1), N>0 stage (point=2), anemia (point=2), bone metastasis free interval≤12 months (point=1), without radiotherapy to primary sites (point=1), and without radiotherapy to first metastasis sites (point=1). The derived prognostic score divided patients into low (score, 0-4) and high (score, 5-8) risk groups, with highly significant differences of 5-year overall survival rates (high vs. low risk: 24.6% vs. 58.2%, HR 3.47, P<0.001). Two external validations presented congruent results. Conclusion: A feasible and applicative prognostic score was successfully established and validated to discriminate bone metastatic nasopharyngeal carcinoma into low/high risk groups, which will be useful for individual treatment.

Overweight/obese status associates with favorable outcome in patients with metastatic nasopharyngeal carcinoma: a 10-year retrospective study.

BACKGROUND: Although the prognostic impact of body mass index (BMI) in patients with non-metastatic nasopharyngeal carcinoma (NPC) had been extensively studied, its effect among metastatic NPC patients remains unknown. The purpose of this study was to evaluate the prognostic effect of BMI in patients with metastatic NPC. METHODS: We retrospectively studied 819 patients who were diagnosed with distant metastasis from NPC and received treatment between 1998 and 2007. The patients were divided into three subgroups according to the World Health Organization classifications for Asian populations: underweight (BMI <18.5 kg/m(2)), normal weight (BMI 18.5-22.9 kg/m(2)), and overweight/obese (BMI ≥23.0 kg/m(2)). The associations of BMI with overall survival (OS) and progression-free survival (PFS) were determined by Cox regression analysis. RESULTS: Of the 819 patients, 168 (20.5%) were underweight, 431 (52.6%) were normal weight, and 220 (26.9%) were overweight/obese. Multivariate analysis adjusted for covariates showed that overweight/obese patients had a longer OS than underweight patients [hazard ratio (HR), 0.64; 95% confidence interval (CI), 0.49-0.84] and normal weight patients (HR, 0.72; 95% CI, 0.57-0.90); no significant difference in PFS was observed among these three groups (P = 0.407). Moreover, in stratified analysis, no statistically significant differences in the effect of overweight/obese status among different subgroups were observed. CONCLUSION: For patients with metastatic NPC, overweight/obese status was associated with longer OS but not longer PFS compared with underweight or normal weight status.

Cytokine-induced killer cells in combination with transcatheter arterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma patients.

This study evaluated the clinical efficacy of autologous cytokine-induced killer (CIK) cell transfusion in combination with transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA), compared to sequential therapy with TACE and RFA, for the treatment of hepatocellular carcinoma (HCC). We retrospectively studied 2 groups of HCC patients: 85 patients in the TACE+RFA+CIK group were treated with adoptive autologous CIK cell transfusion in combination with minimally invasive therapy, 89 patients in the TACE+RFA group were treated with minimally invasive therapy alone. The overall response rate was 76.5% in the TACE+RFA+CIK group and 79.8% in the TACE+RFA group. The disease control rate was higher in the TACE+RFA+CIK group than that in the TACE+RFA group (95.3% vs. 88.8%), but the difference was not significant (P=0.113). Kaplan-Meier analysis showed that the patients in the TACE+RFA+CIK group had significantly longer overall survival (56 vs. 31 mo, P=0.001) and progression-free survival (17 vs. 10 mo, P=0.001) than those in the TACE+RFA group. No severe side effects occurred in the CIK cell transfusion patients. In conclusion, CIK cell immunotherapy may be a valuable therapeutic strategy to prevent recurrence and metastasis in HCC patients after TACE and RFA, and to improve patient prognosis and quality of life. Combined CIK immunotherapy and minimally invasive therapies represent a safe, potential treatment modality for HCC. However, because patient assignment to the 2 treatments was not randomized, any conclusions concerning improvements in survival must be interpreted with great caution.

Comparative survival analysis in patients with pulmonary metastases from nasopharyngeal carcinoma treated with radiofrequency ablation.

PURPOSE: The aim of this retrospective study was to evaluate technical efficacy and the impact of CT-guided pulmonary radiofrequency ablation (RFA) on survival in patients with pulmonary metastases from nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Between 2000 and 2009, 480 patients were pathologically or clinically confirmed pulmonary metastases from NPC. And ten included patients of them had a total of 23 pulmonary metastases treated with percutaneous RFA under the real-time CT fluoroscopy. Safety, local tumor progression, and survival were evaluated in our institutions. Matched-pair survival was compared using Kaplan-Meier analysis. RESULTS: A total of 25 ablations were performed to 23 pulmonary metastases in 13 RFA sessions. Pneumothorax requiring chest tube placement developed in 3 of 13 (23.1%) RFA sessions. The median metastatic overall survival was 36.1 months for all the 480 NPC patients with pulmonary metastases. Furthermore, matched-pair analysis demonstrated patients with RFA treatment had a greater metastatic overall survival than patients without RFA treatment (77.1 months vs 32.4 months, log-rank test, p=0.009). There were no statistically significant differences in the survival probability of patients with RFA treatment (n=10) and surgical resection of pulmonary metastases (n=27) (log-rank test, p=0.75). CONCLUSION: CT-guided pulmonary RFA is safe and offers a treatment alternative for local tumor control, providing promising survival in selected patients with pulmonary metastases from NPC.

CT-guided radiofrequency ablation after with transarterial chemoembolization in treating unresectable hepatocellular carcinoma with long overall survival improvement.

PURPOSE: To assess the time to disease progression (TTP), long-term survival benefit and safety of patients with unresectable hepatocellular carcinoma (HCC) treated with computed tomography (CT)-guided radiofrequency ablation (RFA) with transarterial chemoembolization chemoembolization (TACE). METHODS: This study was approved by the institutional review board. We reviewed the records of patients with intermediate and advanced HCC treated with CT-guided RFA with TACE between January 2000 and December 2009. Median TTP, overall survival (OS) and hepatic function were analyzed with the Kaplan-Meier method and log-rank tests. RESULTS: One hundred and twenty-two patients (112 men and 10 women, mean age 53 years, range 18-86 years) were included in the study. The median follow-up time was 42 months (range 6-89 months), TTP was 6.8 months, the median OS was 31 months, and the 1-, 3-, and 5-year OS were 88.5%, 41.0%, and 10.7%. The results of the univariate analysis revealed that intrahepatic lesion, AJCC stage, and Child-Pugh stage were predictors of OS (P<0.01). In the multivariate analysis, the AJCC stage system showed a statistically significant difference for prognosis. Procedure-related death was 0.21% (1/470) within 1 month, and a statistical difference was found between the TACE and RFA of liver decompensation and Child-Pugh stage (P<0.05). CONCLUSIONS: The survival probabilities of OS increased with CT-guided RFA with TACE, as observed in randomized studies from Europe and Asia. The longest TTP was observed for the intermediate stage HCC. The procedures were well tolerated with acceptable minor and major complications in unresectable HCC patients.

Challenges in the modification of the M1 stage of the TNM staging system for nasopharyngeal carcinoma: A study of 1027 cases and review of the literature.

A series of modifications have been introduced to the TNM staging system over time for nasopharyngeal carcinoma (NPC), mainly focused on the T (primary tumor) and N (local node) components of the system. The M1 stage is a 'catch all' classification, covering a group of patients whose outlook ranges from potentially curable to incurable. Since the current M1 stage does not allow clinicians to stratify patients according to prognosis or guide therapeutic decision-making and allow comparison of results of radical and non-radical treatments, we aimed to subdivide the M1 stage according to a retrospective study of 1027 metastatic NPC patients and to review the relevant literature. Between 1995 and 2007, 1027 inpatients with distant metastasis from NPC were retrospectively analyzed. Various possible subdivisions of the M1 stage were considered, looking at different metastatic sites, the number of metastatic organs and the number of metastases. Survival rates were calculated using the Kaplan-Meier method and compared using the log-rank test. The most frequently involved metastatic sites were the bone, lung and liver. The incidence rates of solitary metastatic lesions and pulmonary metastasis were 16.2 and 41.3%. Despite the poor survival of these patients with a median survival of 30.8 months, patients in the metachronous metastatic group with metastases to the lung and/or solitary lesions, were defined as M1a, and were significantly associated with favorable median survival of 41.5 and 49.1 months in the univariate and multivariate analysis, respectively. Patients in the metachronous metastatic group with metastasis to the lung and/or solitary lesions (M1a) have a more favorable prognosis compared with those patients with multiple metastases located in other anatomic sites (M1b). These data, in one of the largest reported metastatic NPC cohorts, are the first to show the prognostic impact of metastatic status in NPC. As a powerful predictor, the potential clinical value of a modified M1 of the TNM system for NPC will facilitate patient counseling and individualize management.

[Cell cycle arrest at M phase induced by vinblastine in MOLT-4 cells].

This study was purposed to investigate the biological effect of vinblastine (VLS), usually known as inductor of mitotic arrest, on MOLT-4 of ALL cells and to evaluate its significance. The cell arrest in M phase and/or cell apoptosis were induced by treatment of MOLT-4 cells with 0.05 microg/ml VLS for 0 - 12 hours; the DNA histogram was detected by flow cytometry; the morphological changes of cells were observed by confocal microscopy; the cell cycle distribution, cell apoptosis and morphological changes of cells before and after arrest were analyzed by using arrest increasing rate (AIR), arrest efficiency (AE), apoptosis rate (AR) and morphologic parameters respectively. The results indicated that the cell arrest did not accompanied by significant increase of apoptosis rate; the DNA histogram of cell arrest showed dynamic change of cell cycle in time-dependent manner; the arrest efficiency could be quantified. The cell arrest at M phase was accompanied by cell stack in S phase, the cell proliferation rate dropped after cell arrest occurred. The cells arrested at M phase possessed of characteristic morphologic features in cell mitosis. It is concluded that the vinblastine can solely induce arrest of MOLT-4 cells at M phase. This study provides experimental basis for further investigating the relation of cell cycle arrest to apoptosis, mechanism of checkpoint and development of new anticancer drugs.

[Discrimination of anticancer agent action loci at G(2) and M phases by flow cytometry and confocal microscopic imaging].

This study was purposed to evaluate a method to discriminate the action loci of anticancer agents in G(2) and M phases of cell cycle. The meta-amsacrine (m-AMSA) and vinblastine (VBL), already known as G(2) and M phase arrest agent respectively, were used to induce the arrest of MOLT-4 cells at G(2) and M phases, the change of DNA content was detected by flow cytometry, the morphology of arrested cells was observed by confocal microscopy so as to find the arrest efficacy difference of 2 anticancer agents. As a result, the flow cytometric detection showed that the arrested MOLT-4 cells displayed the raise of peaks in G(2) and M phases, but flow cytometric detection alone can not discriminate the difference between them. The observation with confocal microscopy showed that the MOLT-4 cells arrested by m-AMSA displayed the morphologic features in G(2) phase, while the MOLT-4 cells arrested by VBL displayed the morphologic features in M phase. This observation with confocal microscopy is helpful to discriminate the difference between them. In conclusion, the combination of flow cytometry with confocal microscopy is one of the effective methods to discriminate the kind of G(2) or M phase arresting agent of anticancer drugs.