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Editor’s Choice : Hepatocellular Carcinoma Microvessel Density Quantitation with Image Analysis: Correlation with Prognosis
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Abstract: Hepatocellular carcinoma (HCC) has a progression considered to be dependent on angiogenesis. Intratumoral microvessel density (MVD) has been associated with metastasis and recurrence risk; however, selection bias, counting errors, and lack of standardized assessment criteria have limited the clinical utility of angiogenesis quantitation. Therefore, we analyzed HCC angiogenesis with image cytometry using different methods and determined the correlation to prognosis. Tissue microarrays with 135 HCCs were CD31 and CD34 immunostained and quantitated with the Dako ACIS III Image Cytometer labeling index (LI) and Aperio Scanscope XT and MVD algorithm. LI and MVD were compared to each other and to pathologic features and prognosis (recurrence free survival). Using median cutoffs of microvesselquantitation, survival curve analysis showed a statistically significant difference between CD31 MVD algorithm measurement and prognosis (low MVD mean survival = 56.6 months and high MVD mean = 26.5 months; Log-Rank P = 0.0076). Survival was not significantly related to CD31 LI, CD34 LI or CD34 MVD. By linear regression, a direct correlation was observed between CD31 and CD34 using MVD (r = 0.45, P <0.0001), between CD31 MVD and CD31 LI (r = 0.55, P < 0.0001), and between CD31 LI and CD34 LI (r = 0.51, P < 0.0001). In addition, there was a weak but statistically significant relationship between CD31 MVD and CD34 LI (r = 0.25, P = 0.0050). Together, this data confirms previous studies linking angiogenesis to disease prognosis and suggests the utility of MVD image analysis algorithms. Keywords: Hepatocellular carcinoma, microvessel density, immunohistochemistry, prognosis.Download Full Article |
Editor’s Choice : Phase II Study of Irinotecan in Combination with Capecitabine on a 3-Weekly Schedule as First-Line Chemotherapy for Patients with Metastatic or Locally Advanced Colorectal Cancer
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Abstract: Background: Capecitabine has demonstrated non inferiority efficacy and improved safety compared with 5-fluorouracil (5-FU)/leucovorin (LV) in metastatic colorectal cancer (mCRC) without the inconvenience of an infusional therapy. The aim of the present study was to evaluate the efficacy and safety of capecitabine plus irinotecan (CPT-11) given every 3 weeks (XELIRI regimen) as first-line treatment in locally advanced (LA) or mCRC, in order to improve patient tolerability and quality of life. Patients and methods: Patients with LA or mCRC received CPT-11 225 mg/m2 (180 mg/m2 if > 65 years old) on day 1 and capecitabine 1000 mg/m2 (750 mg/m2 if > 65 years old) twice daily on days 2-15 every 3 week. Primary endpoints were objective response rate (ORR) and toxicity of the chemotherapeutic regimen. Secondary endpoints of overall survival (OS), progression-free survival (PFS), response duration and quality of life were also evaluated.
Results: Ninety-one patients were included. In an intention-to-treat analysis, complete response was achieved in 3 patients and partial response in 27, for an ORR of 33%. The disease control rate (ORR + stable disease) was 72.5%. Median time to progression and OS were 9.3 and 17.1 months respectively. Grade 3/4 neutropenia and diarrhea were the most commonly reported adverse vents. Conclusion: The XELIRI regimen given every 3 weeks, as first-line therapy of LA or mCRC was effective and well tolerated, including elderly patients. Severe gastrointestinal toxicities and hematological events were manageable. Keywords: CPT-11, Capecitabine, Irinotecan, XELIRI regimen, Colorectal cancer.Download Full Article |
Editor’s Choice : The Effect of Pretreatment with Chemotherapeutic Drugs on the Susceptibility to Lymphokine Activated CD8+ T Lymphocyte-Mediated Cytotoxicity in CMK Leukemia Cells
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Abstract: Objectives: Certain tumor cells pretreated with chemotherapeutic drugs become more susceptible to death by apoptosis induced by killer cells of the immune system. We examined the CD8+ cytotoxic T lymphocyte (CTL)-mediated cytotoxicity in myeloid leukemia cell lines pretreated with chemotherapeutic drugs. Methods: Peripheral blood mononuclear cells were expanded in vitro in the presence of phytohemagglutinin-P, interleukins-2 and -15. CD3+ CD8+ cells representing the CTLs were isolated using magnetic immunoselection and used in immune cytotoxicity experiments against K562 and CMK leukemia cells, pretreated with two different concentrations of cytarabine and etoposide. Results: In CMK cells pretreated with etoposide at 2 μM and 20 μM concentrations, the mean cell-mediated immune cytotoxicity rose to 21.4 ± 12.9% (p=0.09) and 23.4 ± 12.6% (p=0.046), respectively, when compared to the control value of 6.6 ± 3.8%. In CMK cells pretreated with cytarabine at 1 μM and 10 μM concentrations, the mean immune cytotoxicity rose to 14.3 ± 11.2% and 22.6 ± 15.2%, respectively, compared to the control value of 8.7 ± 6.3%, although these results did not reach statistical significance. However, a similar increase in CTL-mediated immune cytotoxicity was not observed against drug-treated K562 cells. Conclusion: This study suggests that pretreatment with chemotherapeutic drugs can render CMK leukemia cells more susceptible to immune attack by activated CTLs. Further studies are needed to explore this phenomenon, to establish an immune-enhancing effect of pretreatment with chemotherapy in the treatment of leukemia. Keywords: Leukemia, cytotoxic T lymphocytes, chemotherapy, apoptosis.Download Full Article |
Editor’s Choice : Role of Primary Tumour Resection and Addition of Bevacizumab to Chemotherapy in the Management of Advanced Colorectal Cancer with Inoperable Metastasis: A Retrospective Analysis
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Abstract: Purpose:To analyze the impact of primary tumour resection on treatment outcomes in patients with advanced colorectal cancer (CRC) and inoperable metastases at diagnosis in combination with optimal systemic therapy. Methods:A retrospective study was carried out in four hospitals in Valencia (Spain) including all consecutive patients diagnosed between 1/2009 and 12/2010 of advanced CRC with inoperable metastasis and treated with a fluoropyrimidine and oxaliplatin combination chemotherapy regimens with or without bevacizumab (B). Treatment outcomes were compared between patients undergoing or not primary tumour resection. Results:A total of 112 patients met inclusion criteria: 62 patients underwent resection of the primary tumour (Group 1) and 50 were treated with exclusive chemotherapy (Group 2). Globally, patients in group 2 presented more disfavorable characteristics. Forty-five (72%) and 31 (62%) patients received chemotherapy with bevacizumab respectively. Overallresponse rate(ORR) were 67% in Group 1 and 56% in Group 2. There were no statistically significant differences between the two groups in progression free survival (PFS) (12 vs. 10 months; p =0.11) and overall survival (OS) (27 vs. 22 months; p 0.1). B regimens increased ORR (73% vs. 42%; p = 0.003) and PFS (12 vs. 11 months; p = 0.019) but not OS. Complications were higher in the group of patients without primary tumour resection, particularly when associated to B regimens. Conclusions:Primary tumour resection offers no survival gain for patients with advanced CRC and inoperable metastases. Benefits of adding Bevacizumab to standard chemotherapy were similar in both groups, but it increases the risk of complications in non-resected patients. Keywords: Primary Tumour Resection, Advanced Colorectal Cancer, Metastases, Survival, Bevacizumab.Download Full Article |
