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  • 11
    Publication Date: 2014-05-31
    Description: We conducted a comprehensive systematic review of the literature on volumetric parameters and a meta-analysis of the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with head and neck cancer (HNC). Methods: A systematic search of MEDLINE and EMBASE was performed using the key words PET, head and neck, and volume. Inclusion criteria were 18 F-FDG PET used as an initial imaging tool; studies limited to HNC; patients who had not undergone surgery, chemotherapy, or radiotherapy before PET scans; and studies reporting survival data. Event-free survival and overall survival were considered markers of outcome. The impact of MTV or TLG on survival was measured by the effect size hazard ratio (HR). Data from each study were analyzed using Review Manager. Results: Thirteen studies comprising 1,180 patients were included in this study. The combined HR for adverse events was 3.06 (2.33–4.01, P 〈 0.00001) with MTV and 3.10 (2.27–4.24, P 〈 0.00001) with TLG, meaning that tumors with high volumetric parameters were associated with progression or recurrence. Regarding overall survival, the pooled HR was 3.51 (2.62–4.72, P 〈 0.00001) with MTV and 3.14 (2.24–4.40, P 〈 0.00001) with TLG. There was no evidence of significant statistical heterogeneity at an I 2 of 0%. Conclusion: MTV and TLG are prognostic predictors of outcome in patients with HNC. Despite clinically heterogeneous HNC and the various methods adopted between studies, we can confirm that patients with a high MTV or TLG have a higher risk of adverse events or death.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 12
    Publication Date: 2014-08-02
    Description: This was a study to compare the diagnostic efficacies of endoscopic ultrasonography (EUS), CT, PET/MR imaging, and PET/CT for the preoperative local and regional staging of esophageal cancer, with postoperative pathologic stage used as the reference standard. Methods: During 1 y, 19 patients with resectable esophageal cancer were enrolled and underwent preoperative EUS, CT, PET/CT, and PET/MR imaging. A chest radiologist and nuclear medicine physician retrospectively reviewed the images and assigned tumor and lymph node stages according to the seventh version of the TNM system and the American Joint Committee on Cancer staging system. Four patients who were treated nonsurgically were excluded from data analysis. The efficacies of EUS, CT, PET/CT, and PET/MR imaging were compared. Results: Primary tumors were correctly staged in 13 (86.7%), 10 (66.7%), and 5 (33.3%) patients at EUS, PET/MR imaging, and CT, respectively ( P value ranging from 0.021 to 0.375). The accuracy of determining T1 lesions was 86.7%, 80.0%, and 46.7% for EUS, PET/MR imaging, and CT, respectively. For distinguishing T3 lesions, the accuracy was 93.3% for EUS and 86.7% for both PET/MR imaging and CT. For lymph node staging, the accuracy was 83.3%, 75.0%, 66.7%, and 50.0% for PET/MR imaging, EUS, PET/CT, and CT, respectively. In addition, area-under-the-curve values were 0.800, 0.700, 0.629, and 0.543 for PET/MR imaging, EUS, PET/CT, and CT, respectively. Conclusion: PET/MR imaging demonstrated acceptable accuracy for T staging compared with EUS and, although not statistically significant, even higher accuracy than EUS and PET/CT for prediction of N staging. With adjustments in protocols, PET/MR imaging may provide an important role in preoperative esophageal cancer staging in the future.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 13
    Publication Date: 2013-12-13
    Description: Somatic heterozygous mutations of the DNA methyltransferase gene DNMT3A occur frequently in acute myeloid leukemia and other hematological malignancies, with the majority (~60%) of mutations affecting a single amino acid, Arg882 (R882), in the catalytic domain. Although the mutations impair DNMT3A catalytic activity in vitro, their effects on DNA methylation in cells have not been explored. Here, we show that exogenously expressed mouse Dnmt3a proteins harboring the corresponding R878 mutations largely fail to mediate DNA methylation in murine embryonic stem (ES) cells but are capable of interacting with wild-type Dnmt3a and Dnmt3b. Coexpression of the Dnmt3a R878H (histidine) mutant protein results in inhibition of the ability of wild-type Dnmt3a and Dnmt3b to methylate DNA in murine ES cells. Furthermore, expression of Dnmt3a R878H in ES cells containing endogenous Dnmt3a or Dnmt3b induces hypomethylation. These results suggest that the DNMT3A R882 mutations, in addition to being hypomorphic, have dominant-negative effects.
    Keywords: Myeloid Neoplasia, Brief Reports
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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