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

<p><b>INTRODUCTION</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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].</p><p><b>CONCLUSIONS</b>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.</p>

Establishment of a specific serum proteomic profile model for liver organ-specific metastasis of nasopharyngeal carcinoma by matrix-assisted laser desorption/ionization time of flight mass spectrometry / 肿瘤

Objective: To investigate the specific serum peptide profile of LM (liver metastasis) associated with NPC (nasopharyngeal carcinoma) by comparing the patients who have NPC with LM and without LM and the patients with LM not from NPC, and to provide the model for diagnosis of LM from NPC. Methods: Pre-treatment serum samples from 50 patients who had pathologically confirmed NPC and 14 patients who had pathologically confirmed non-NPC with LM were collected and assayed by MALDl-TOF-MS (matrix-assisted laser desorption/ionization time of flight mass spectrometry) analysis. During follow-up of more than 3 years after radiotherapy, 16 NPC patients with LM (LM NPC group), 16 NPC patients with non-LM (non-LM NPC group) and 18 NPC pateints without metastasis (non-M NPC group) were confirmed. Mass spectrographic data were analyzed with ClinProt software Tools. The specific serum peptide model of NPC-associated LM was established by using both data mining analysis and decision tree classification analysis. Results: Differential expressions of 28 peptide peaks were detected between LM NPC group and non-M NPC group, 9 peptide peaks between LM NPC group and non-LM NPC group, 45 peptide peaks between LM NPC group and LM non-NPC group, and 10 peptide peaks between non-LM NPC group and non-M NPC group. Using comparative proteomics analysis, 4 protein mass peaks (their mass to charge ratios were 4 155.34 m/z, 4 194.87 m/z, 4 210.78 m/z and 4 249.56 m/z, respectively) were identified as the liver-specific metastasis-associated protein peaks in NPC. The models based on the 4 sieved markers of NPC could discriminate LM NPC group from non-LM NPC group, non-M NPC group and non-NPC LM group. The recognition capability was 100.0% and the cross-validation of these models for differentiating the above 4 groups were 73.3%-100.0%. Conclusion: NPC with LM has a specific serum peptide profile. The established specific serum peptide model may have certain application in the diagnosis of LM associated with NPC, and provide a clinical diagnostic platform for detecting potential liver-specific metastasis-associated biomakers in NPC. Copyright © 2013 by TUMOR.

Efficacy of minimally invasive therapies on unresectable pancreatic cancer / 癌症

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.

Evaluation of the prognostic significance of refinement and stratification of distant metastasis status in 1016 cases of nasopharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

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

<p><b>BACKGROUND AND OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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<AFP<37.5 ng/mL) after curative TACE plus RFA treatment, the 1-year recurrence rate was 28.57% for the study group and 80% for the control group. The time to recurrence in the study group was also longer than that in the control group (mean 10.2 months vs. 6.8 months). After CIK cell infusions, the percent of CD3+CD4+ T cells and CD4+ /CD8+ T cells increased from 28.1+/-5.9% and 0.9+/-0.3% to 32.7+/-3.6% and 1.2+/-0.2% (P<0.001 and=0.004, respectively), while the percent of CD3+CD8+ T cells decreased from 32.9+/-8.4% to 28.8+/-2.2% (P=0.046). Also the percentage of patients with hepatitis B virus (HBV)-DNA content less than 1x10(3) copies/mL was 73.5% in the study group and 9.1% in the control group.</p><p><b>CONCLUSIONS</b>CIK cells transfusion may reduce the level of serum AFP and anti-HBV and decrease the 1-year recurrence rate of patients with HCC after curative TACE plus RFA. Serum AFP decrease after CIK cell treatment may serve as a useful marker for predicting immunotherapy clinical outcome in patients with HCC undergone curative minimally invasive therapy.</p>

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

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.

Discrimination of anticancer agent action loci at G(2) and M phases by flow cytometry and confocal microscopic imaging / 中国实验血液学杂志

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.

Cell cycle arrest at M phase induced by vinblastine in MOLT-4 cells / 中国实验血液学杂志

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.