Biomedical subjects
Neal M Lonky
Publications and source records attributed to Neal M Lonky.
Transepithelial sampling of the uterine ectocervix with a stiff-bristled, spiral-shaped brush.
OBJECTIVE: To measure the depth of sampling of the uterine ectocervix with the use of a stiff-bristled, spiral-shaped brush (SpiraBrush Cx; Trylon Corporation, Torrance, CA). MATERIALS AND METHODS: Eligible hysterectomy specimens were identified. The ectocervix was brushed with an inked SpiraBrush Cx in four quadrants with either light (gentle) or heavy (forceful) pressure. The depth of sampling was determined histologically. RESULTS: Four normal uteri were sampled a total of 15 times. The entire epithelium was removed to the epithelial-stromal junction in three specimens and in one sample only a few basal cells remained with light pressure. The depth of sampling ranged from 0.2 mm to 0.4 mm. Heavy pressure resulted in the entire removal of epithelium in six samples, with the depth of sampling ranging from 0.2 mm to 0.7 mm. The stroma was disrupted in one sample. Results were uninformative in five samples. CONCLUSIONS: Sampling of the uterine ectocervix with the SpiraBrush Cx seems to be transepithelial in most cases.
False-negative hybrid capture II results related to altered adhesion molecule distribution in women with atypical squamous cells pap smear results and tissue-based human papillomavirus-positive high-grade cervical intraepithelial neoplasia.
OBJECTIVE: We investigated the detection of high-risk human papillomavirus DNA with the Hybrid Capture II test (HCII; Digene Corporation, Beltsville, MD) and the presence and pattern of distribution of adhesion molecules in biopsy-proven high-grade neoplastic lesions containing high-risk HPV-DNA from women with ASC cytology results. MATERIALS AND METHODS: We screened 4,600 women and performed colposcopy in 278 women with atypical squamous cells cytologic results. All women underwent HCII and tissue-based polymerase chain reaction analysis for high-risk HPV subtypes. Of 33 women with cervical intraepithelial neoplasia (CIN) 2 or worse biopsy results, 27 biopsy specimens contained sufficient tissue to perform immunohistochemical testing (pathologist blinded as to cytologic and HCII results) for adhesion molecules beta-catenin and 21 cases for E-cadherin. RESULTS: Five of 27 specimens with CIN 2 or worse biopsy results (18.5%) had negative HCII results. All five specimens showed evidence of high-risk human papillomavirus by polymerase chain reaction analysis. All five showed full-thickness distribution via immunohistochemical staining for beta-catenin. There was sufficient tissue to examine four of five specimens for E-cadherin, and a full-thickness distribution also was documented. CONCLUSIONS: Previous research linked false-negative cytologic results in women with high-grade CIN to altered adhesion molecule distribution and impaired exfoliation, and a similar phenomenon may be responsible for false-negative HCII results in women with atypical squamous cells cytologic results and high-grade CIN.
Triage of atypical squamous cells of undetermined significance with hybrid capture II: colposcopy and histologic human papillomavirus correlation.
OBJECTIVE: To estimate the effectiveness of Hybrid Capture II to predict high-grade cervical intraepithelial neoplasia (CIN) from a cytological cervical sample. Evidence of high-risk human papillomavirus (HPV) was also determined from biopsy samples using the polymerase chain reaction (PCR) for women referred with atypical squamous cells of undetermined significance (ASCUS) Papanicolaou smears. METHODS: We screened 8170 women with Papanicolaou smears, of whom 278 (3.4%) returned ASCUS. All ASCUS cases underwent colposcopy and Hybrid Capture II testing. High-grade CIN biopsy specimens were tested for high-risk HPV by PCR. RESULTS: Nearly 30% of ASCUS cases had CIN biopsy results (11.9% showing CIN II or CIN III and 17.6% showing CIN I). Hybrid Capture II positive rates were 93.3% for cases with CIN III, 72.2% for CIN II, and 51.0% for CIN I (P <.001). ASCUS-Premalignant Process Favored cases showed a 28.1% high-grade biopsy rate and a 100% Hybrid Capture II positive rate. For ASCUS-Undefined and ASCUS-Reactive Process Favored cases, Hybrid Capture II returned positive in 90.9% of CIN III and 61.5% of CIN II cases (P <.001). Sixty-nine of 178 (38.8%) patients with no evidence of CIN tested positive for Hybrid Capture II. Human papillomavirus deoxyribonucleic acid (DNA) high-risk subtypes were detected by PCR in the tissue of all high-grade CIN cases with negative Hybrid Capture II results. CONCLUSION: Hybrid Capture II returned negative in 25% of cases with biopsy-proven high-grade CIN with associated high-risk HPV DNA by PCR (non-Premalignant ASCUS subset), and positive in 39.3% of cases with normal results; this limits its clinical utility.
A stiff bristled, spiral-shaped ectocervical brush: a device for transepithelial tissue biopsy.
OBJECTIVE: To compare a new spiral-shaped tissue-sampling brush with a standard cervical punch biopsy. METHODS: Before large loop excision of the transformation zone, women with cervical intraepithelial neoplasia underwent a transepithelial brush biopsy of a portion of a colposcopically identified lesion, followed by a punch biopsy of the remaining portion. Brush biopsy samples were processed using liquid-based cytology and cell block techniques. Diagnoses were made using a consensus of three pathologists. Brush biopsy samples without basal cells were considered inadequate. The histological diagnosis was compared with the brush biopsy and punch biopsy samples. Patient-reported pain and physician-reported bleeding for punch and brush biopsies were compared. RESULTS: Fifty-two women were enrolled in the study; 47 successfully completed the study protocol. Eight brush biopsy specimens were inadequate. Thirty-nine women showed abnormal pathology (human papillomavirus/cervical intraepithelial neoplasia I or worse) on large loop excision of the transformation zone, and 32 women had high-grade (or worse) lesions. The punch biopsy correlated with high-grade disease in 53.1% of these women. The brush biopsy result correlated with high-grade disease in 79.3% of these women using a cell block technique and 76.7% using liquid cytology. There was significantly less pain (P <.001) and significantly less bleeding (P <.001) with the brush biopsy. CONCLUSION: When an adequate sample is collected, spiral brush biopsy is as good as a standard punch biopsy for detecting cervical pathology, with substantially less pain and bleeding. User training and guidelines for sampling are needed to assure that an adequate sample is collected.
Reducing death from cervical cancer examining the prevention paradigms.
The prevention of morbidity and mortality from cervical cancer will hinge upon our understanding of the epidemiology, the molecular basis, and natural history of the disease and its associated precursors. This article serves as an introduction and presents our current challenge to prevent or find all women at risk, and alter the course of disease to effect a regression or a cure.
Risk factors related to the development and mortality from invasive cervical cancer clinical utility and impact on prevention.
The focus of this article is to explore the various risk factors related to cervical cancer and the practical context in which they can be applied. The ability to link dinical outcomes (disease presence, persistence, progression, and recurrence) with antecedent risk factors is strengthened by a new understanding of the molecular mechanisms that are responsible for malignant transformation.
Aberrant expression of E-cadherin in cervical intraepithelial neoplasia correlates with a false-negative Papanicolaou smear.
OBJECTIVES: E-cadherin is responsible for cell adhesion in normal cervical epithelium. It is normally absent in the superficial epithelial layers, allowing for exfoliation. We investigated the correlation between E-cadherin distribution and Papanicolaou smear in subjects with cervical dysplasia. STUDY DESIGN: Tissue samples from 25 women with cervical dysplasia were tested for E-cadherin, beta-catenin, and alpha-catenin expression by immunohistochemistry. The expression pattern of these proteins, whether full thickness or restricted to the basal layers, was correlated with the Papanicolaou smear result. RESULTS: Of 12 women with normal Papanicolaou smears, 10 of 11 informative cases demonstrated E-cadherin expression throughout all epithelial layers. Eight of 10 informative cases with an abnormal Papanicolaou smear showed E-cadherin only at the basal layers. Alpha-catenin was distributed throughout the entire epithelium in samples of all 25 women. CONCLUSIONS: Expression of E-cadherin throughout all epithelial layers was correlated with a false-negative Papanicolaou smear. It is likely that aberrant persistence of E-cadherin in these lesions interferes with the exfoliation of abnormal cells.