Calcified lymph nodes in the setting of head and neck squamous cell carcinoma: A predictor of HPV positivity?

PURPOSE: Human papillomavirus (HPV) is an important cause of head and neck squamous cell carcinoma (HNSCC) and accounts for a large majority of new cases. The purpose of this study is to determine whether there is an association between nodal calcification and HPV positivity in the setting of metastatic HNSCC. METHODS: Consecutive patients with HNSCC who underwent CT were retrospectively identified. Patients were then divided into two groups: those with HPV-positive HNSCC and those with HPV-negative HNSCC. Demographic, clinical, and CT data were compared between the two groups to determine factors associated with HPV-positive HNSCC. RESULTS: A total of 179 patients with HNSCC were included in the final analyses, 104 (58%) of whom had HPV-positive tumors. Univariate analyses demonstrated that those with HPV-positive HNSCC were more likely to have calcified lymph nodes (p = 0.044). Analyses also confirmed previously known associations with male gender (p = 0.001), primary oropharyngeal tumors (p < 0.001), and cystic lymph nodes (<0.001). The HPV-positive HNSCC group was also less likely to have necrotic lymph nodes (p < 0.001). CONCLUSION: In addition to known clinical and imaging factors associated with HPV-positive metastatic HNSCC, such as male gender, oropharyngeal primary location, and cystic lymph nodes, the presence of calcifications within cervical lymph nodes, although infrequent, provides an additional useful feature to predict HPV positivity in HNSCC. Additionally, if calcified lymph nodes are present, then a primary oropharyngeal tumor site should be considered.

Development of a standardized method for contouring the larynx and its substructures.

OBJECTIVES: Limiting radiation dose to the larynx can diminish effects of laryngeal dysfunction. However, no clear guidelines exist for defining the larynx and its substructures consistently on cross-sectional imaging. This study presents computed tomography (CT)- and magnetic resonance imaging (MRI)-based guidelines for contouring laryngeal organs-at-risk (OARs). MATERIALS AND METHODS: Standardized guidelines for delineating laryngeal OARs were devised and used to delineate on CT and MRI for head-and-neck cancer patients. Volumetric comparisons were performed to evaluate consistency and reproducibility of guideline-based contours. RESULTS: For the initial 5 patients the mean CT and MRI based larynx volume did not differ significantly between imaging modalities; 34.39 ± 9.85 vs. 35.01 ± 9.47 (p = .09). There was no statistical difference between the CT based mean laryngeal volume in the subsequent 44 patients compared to the initial 5 patients outlined on CT and the MRI scan (p = 0.53 and 0.62). The OAR volume for laryngeal substructures were not statistically different among patients or between imaging modalities. Once established, the guidelines were easy to follow. CONCLUSION: The guidelines developed provide a precise method for delineating laryngeal OARs. These guidelines need to be validated and clinical significance of outlining laryngeal substructures and dose-volume constraints should be investigated before routine implementation in clinic practice.

Imaging in the evaluation of headache.

When deciding to perform imaging for headache, it is important to consider many factors including the pretest probability, prevalence of diseases, sensitivity of imaging, and implications for treatment. For the first presentation of a headache or a change in headache pattern, if the characteristics do not perfectly fit a primary headache type, imaging may be indicated according to the ICHD-2 criteria to exclude a secondary cause before a primary headache is diagnosed. The value of negative imaging should not be underestimated in the cost-benefit analysis, which often only takes into account number needed to treat or likelihood of finding a significant treatable abnormality. One study has shown that some groups of patients are less likely to overuse other parts of the health care system after negative neuroimaging. Further studies with stronger methodologies, finer differentiation of acute and chronic headache presentations, more advanced imaging technology, among other factors, can improve decision making on when to use imaging and assess the impact of imaging on patient satisfaction and quality of life. In addition, functional MRI, MRS, and voxel-based morphometry MRI are only some of the neuroimaging techniques currently used in research to further understand the pathophysiology and mechanisms of headache. In conclusion, although most headaches are a primary headache disorder with a benign course, imaging is an important part of the diagnostic evaluation to exclude the presence of a secondary cause of headache that could cause fatal results or severe neurologic morbidity. In headache patients without focal neurologic examination abnormalities, the yield of neuroimaging for significant intracranial findings is generally low. However, specific subgroups of headache patients and headache presentations can have much higher rates of significant intracranial abnormalities.

Interleukin-12 up-regulates Fas expression in human osteosarcoma and Ewing's sarcoma cells by enhancing its promoter activity.

Interleukin-12 (IL-12) has shown significant antitumor activity in several preclinical animal tumor models. Our previous studies showed that IL-12 inhibited tumor growth in human osteosarcoma and Ewing's sarcoma animal model. Decreased Fas expression in osteosarcoma increased the lung metastatic potential. In this study, we further examined the mechanism of IL-12 antitumor activity and showed that IL-12 significantly increased Fas expression in both human osteosarcoma cells LM7 and Ewing's sarcoma cells TC71. Up-regulation of Fas expression increased their sensitivity to Fas-induced cell apoptosis. Constructs of the Fas promoter linked to a luciferase reporter gene were used to determine the promoter activity. IL-12 increased Fas promoter activity 4.2- and 4.9-fold in TC71 and LM7 cells, respectively. Time course studies have shown that recombinant IL-12 stimulated Fas promoter activity at 2 hours, reached the peak level at 4 hours, and then declined at 24 hours. To investigate whether IL-12 specifically enhanced Fas promoter activity, we determined whether another gene (E1A) was able to stimulate Fas promoter activity. We also evaluated effect of IL-12 on the topoisomerase IIalpha promoter. The results indicated that E1A but not IL-12 stimulated topoisomerase IIalpha promoter activity. E1A failed to increase Fas promoter activity. We also found that kappaB-Sp1 element at position -295 to -286 in Fas promoter was essential for IL-12-induced activation, and nuclear factor-kappaB transcription factor was activated after IL-12 treatment in TC71 cells. These results indicate that IL-12 up-regulates Fas expression in human osteosarcoma and Ewing's sarcoma by enhancing Fas promoter activity. Understanding this mechanism may lead to new therapeutic approaches for the treatment of sarcoma involving the use of IL-12.

Classification analysis of the transcriptosome of nonlesional cultured dermal fibroblasts from systemic sclerosis patients with early disease.

OBJECTIVE: To compare the transcriptosome of early-passage nonlesional dermal fibroblasts from systemic sclerosis (SSc) patients with diffuse disease and matched normal controls in order to gain further understanding of the gene activation patterns that occur in early disease. METHODS: Total RNA was isolated from early-passage fibroblasts obtained from nonlesional skin biopsy specimens from 21 patients with diffuse SSc (disease duration <5 years in all but 1) and 18 healthy controls who were matched to the cases by age (+/-5 years), sex, and race. Array experiments were performed on a 16,659-oligonucleotide microarray utilizing a reference experimental design. Supervised methods were used to select differentially expressed genes. Quantitative polymerase chain reaction (PCR) was used to independently validate the array results. RESULTS: Of the 8,324 genes that passed filtering criteria, classification analysis revealed that <5% were differentially expressed between SSc and normal fibroblasts. Individually, differentially expressed genes included COL7A1, COL18A1 (endostatin), DAF, COMP, and VEGFB. Using the panel of genes discovered through classification analysis, a set of model predictors that achieved reasonably high predictive accuracy was developed. Analysis of 1,297 gene ontology (GO) classes revealed 35 classes that were significantly dysregulated in SSc fibroblasts. These GO classes included anchoring collagen (30934), extracellular matrix structural constituent (5201), and complement activation (6958, 6956). Validation by quantitative PCR demonstrated that 7 of 7 genes selected were concordant with the array results. CONCLUSION: Fibroblasts cultured from nonlesional skin of patients with SSc already have detectable abnormalities in a variety of genes and cellular processes, including those involved in extracellular matrix formation, fibrillogenesis, complement activation, and angiogenesis.