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1.  Application of Magnetic-Resonance-Spectroscopy-Based Metabolomics to the Fine-Needle Aspiration Diagnosis of Papillary Thyroid Carcinoma 
Acta Cytologica  2011;55(6):584-589.
This study explores the potential use of high-resolution magic angle spinning proton magnetic resonance spectroscopy as an ancillary diagnostic technique for papillary thyroid carcinoma in thyroid fine-needle aspiration biopsies. The method has already been shown to be effective in the classification of various other nonthyroid cancers.
Study Design
Twenty-six samples (13 paired cytologic and histologic samples) from patients being evaluated for thyroid abnormalities at the Massachusetts General Hospital were spectroscopically analyzed, and included: papillary thyroid carcinomas (n = 4), follicular adenomas (n = 4), and normal thyroid samples (n = 5). Metabolic profiles were statistically generated based on the spectroscopy results, which were then correlated with the final cytologic and histologic diagnoses from the same samples to determine the diagnostic capacity of the profiles.
Principal component analysis of the tissue samples revealed statistically significant correlations among principal components and various cytologic and histologic features. Canonical score 1, calculated with principal components in correlation with analyzed pathologies, revealed the ability of the metabolic profile to differentiate all three examined histologic tissue groups (ANOVA, p < 0.0001). Applying coefficients of principal components and canonical scores obtained with tissue samples directly onto spectral results of cytology samples, the calculated canonical score 1 also revealed similar trends among the three fine-needle aspiration biopsy groups. In particular, the papillary thyroid carcinoma group exhibited significant differences from both the adenomatous and normal cytology groups (p < 0.0170).
The results indicate the potential of high-resolution magic angle spinning proton magnetic resonance spectroscopy as an ancillary marker for papillary thyroid carcinoma in fine-needle aspiration biopsy specimens.
PMCID: PMC3254028  PMID: 22156470
Thyroid cancer; Diagnosis; Magnetic resonance spectroscopy; Metabolomics; Fine-needle aspiration biopsy
2.  A Comparison of Dacron versus Flocked Nylon Swabs for Anal Cytology Specimen Collection 
Acta Cytologica  2011;55(4):364-367.
We compared the performance of commonly used Dacron versus flocked nylon swabs for anal cytology.
Study Design
From 23 HIV-positive men screened at Kaiser Permanente San Francisco (San Francisco, Calif., USA), 2 anal specimens were collected, 1 with each swab in random order, and placed into liquid cytology medium. Specimens were tested for cellularity by quantifying a genomic DNA (erv-3). The number of cells was assessed from prepared slides by automated image analysis. Performance was compared between swabs using 2-sample t tests and standard crossover trial analysis methods accounting for period effect.
Flocked swabs collected slightly more erv-3 cells than Dacron for the first sample although not significantly (p = 0.18) and a similar number of erv-3 cells for the second sample (p = 0.85). Flocked swabs collected slightly more cells per slide than the Dacron swabs at both time periods although this was only significant in the second time period (p = 0.42 and 0.03 for first and second periods, respectively). In crossover trial analysis, flocked swabs outperformed Dacron for cell count per slide based on slide imaging (p = 0.03), but Dacron and flocked swabs performed similarly based on erv-3 quantification (p = 0.14).
Further studies should determine whether flocked swabs increase the representation of diagnostically important cells compared to Dacron.
PMCID: PMC3150956  PMID: 21791907
Cytology; Anal neoplasia; Human papillomavirus testing; Screening; Cytological techniques
3.  Quantitative Automated Image Analysis System with Automated Debris Filtering for the Detection of Breast Carcinoma Cells 
Acta Cytologica  2011;55(3):271-280.
To develop an intraoperative method for margin status evaluation during breast conservation therapy (BCT) using an automated analysis of imprint cytology specimens.
Study Design
Imprint cytology samples were prospectively taken from 47 patients undergoing either BCT or breast reduction surgery. Touch preparations from BCT patients were taken on cut sections through the tumor to generate positive margin controls. For breast reduction patients, slide imprints were taken at cuts through the center of excised tissue. Analysis results from the presented technique were compared against standard pathologic diagnosis. Slides were stained with cytokeratin and Hoechst, imaged with an automated fluorescent microscope, and analyzed with a fast algorithm to automate discrimination between epithelial cells and noncellular debris.
The accuracy of the automated analysis was 95% for identifying invasive cancers compared against final pathologic diagnosis. The overall sensitivity was 87% while specificity was 100% (no false positives). This is comparable to the best reported results from manual examination of intraoperative imprint cytology slides while reducing the need for direct input from a cytopathologist.
This work demonstrates a proof of concept for developing a highly accurate and automated system for the intraoperative evaluation of margin status to guide surgical decisions and lower positive margin rates.
PMCID: PMC3101495  PMID: 21525740
Imprint cytology; Breast conservation therapy; Computer-aided diagnosis; Fluorescent microscopy
4.  Diverse and High Prevalence of Human Papillomavirus Associated with a Significant High Rate of Cervical Dysplasia in Human Immunodeficiency Virus–Infected Women in Johannesburg, South Africa 
Acta cytologica  2009;53(1):10-17.
To evaluate the epidemiology of the human papillomavirus (HPV) type and correlate it with the Papanicolaou smears in human immunodeficiency virus–seropositive women in Johannesburg, South Africa.
Study Design
In a cohort of 148 women, HPV DNA testing was performed with the Roche HPV genotyping test (Branchburg, New Jersey, U.S.A.). Papanicolaou smears were performed by standard cytology utilizing 2001 Bethesda reporting guidelines.
The average age and CD4 count of the participants was 35 years and 255 cells per mm3, respectively. Fifty-four percent had abnormal Papanicolaou smears; 66% of the abnormal cytology was low grade changes, with 33% assessed as having high grade changes. HPV DNA was found in 95% of the 148 subjects assessed, with 83% having 1 or more HPV oncogenic types. Common oncogenic types were 16, 35, 53 and 18. When HPV results were stratified by CD4, there was a significant risk of an oncogenic HPV type in women with CD4 <200. Significant odds ratios for high grade lesions were seen in HPV types 16, 35, 51, 66, 69 and 73.
The results of HPV typing illustrate the diverse range of oncogenic HPV and high prevalence of oncogenic type. These results highlight the need for improved access to Papanicolaou smear screening for this population.
PMCID: PMC2922752  PMID: 19248549
cervical dysplasia; HIV; human papillomavirus type 16; uterine cervical diseases

Results 1-4 (4)