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Biomedical subjects

M A Duggan

Publications and source records attributed to M A Duggan.

At least 19 recordsLinked to original sources
PubMed2006

Comparative study of the ThinPrep Pap test and conventional cytology results in a Canadian cohort.

OBJECTIVE: To compare the frequency of Pap test results in a prospective series of direct to vial ThinPrep tests to a cohort of conventionally prepared tests. To follow-up all test results for a minimum of 2 years and assess performance based on this outcome. METHODS: All women presenting for either routine screening or colposcopic examination in 2001 were enrolled in the ThinPrep cohort. A similar, population of conventionally prepared tests was extracted from the year 2000 laboratory data. Information on all concurrent and follow-up cervical specimens over the ensuing 2 years was retrieved. RESULTS: The ThinPrep cohort comprised 2288 Pap tests and the conventional, 2211. The frequency of normal [within normal limits (WNL) and benign cellular changes (BCC)] results in the ThinPrep cohort was 6% lower and the frequency of abnormal [> or =atypical squamous cells of undetermined significance (ASCUS)] results was 6.8% higher. Respective ThinPrep and conventional cohort results were 1156 (51%) and 1291 (58%) WNL, 625 (27%) and 561 (25%) BCC, 101 (4%) and 65 (3%) ASCUS, 21 (1%) and 2 (0.1%) atypical glandular cells of undetermined significance, 301 (13%) and 224 (10%) low-grade squamous intraepithelial lesion (LSIL), and 74 (3%) and 40 (2%) high-grade SIL (HSIL) (P < 0.0001). Follow-up was available for nearly 80% of each cohort. LSIL or higher was confirmed in 57.5% (n = 266) of the abnormal ThinPrep and 60.9% (n = 190) of the abnormal conventional tests. The ThinPrep yield of confirmed tests however was almost 50% higher than the conventional test. CONCLUSION: In this population, ThinPrep was superior to the conventional Pap test.

Adult↗
PubMed2004

ERCP-directed brush cytology prepared by the Thinprep method: test performance and morphology of 149 cases.

Conventionally prepared endobiliary brushings are moderately (42%) sensitive and highly (98%) specific in detecting malignancy. The performance and morphological features of brushings prepared by Thinprep, a liquid-based method are mostly unknown. All brushings were retrieved from the laboratory files. Disease was classified as benign or malignant by linkage with the provincial cancer registry and sensitivity, specificity, positive (PPV) and negative predictive values (NPV) calculated. True positives and negatives were reviewed and predictive morphological features analysed by regression tree analysis. Out of 149 brushings, 55 (37%) were positive and 94 (63%) negative. Malignancy was identified in 86 (58%) and benign disease in 63 (42%) of the cases. The sensitivity was 51%, specificity 83%, PPV 80% and NPV 55%. Absolute discriminants of positive and negative brushings were not found, but nuclear cytoplasmic ratio was a useful feature. The performance of Thinprep-prepared brushings from this anatomical site was comparable with conventional preparations.

Adolescent↗
PubMed2001

The accuracy and interobserver reproducibility of endometrial dating.

Although controversial, diagnosis of luteal phase defect (LPD) includes the morphological assessment of endometrial development. This study was conducted to determine if refresher training in the histological criteria could improve the accuracy and interobserver reproducibility of endometrial dating. Seventy-eight endometrial biopsies were dated by a reference panel of two pathologists and then reviewed twice by a study panel of four pathologists. In the first review, usual practice was applied. Prior to the second review, they studied a standard document of histological criteria. Samples were dated as proliferative, secretory (post-ovulatory day, POD), menstrual, and undatable. Accuracy levels based on the reference dating and agreement levels using kappa values were calculated per review and compared. The kappa for overall dating was 0.683 in the first review and 0.696 in the second. The respective first and second review kappa values were 0.736 and 0.771 for proliferative, and 0.794 and 0.764 for secretory. Amongst those dated as secretory in the first and second reviews, respectively, 31 and 28% were assigned the same POD by any two panellists, 68 and 63% were dated to within 1 day, and 77 and 71% were dated to within 2 days. Accuracy levels per panellist for overall dating were very high in both reviews but were low for individual PODs. Accuracy and interobserver reproducibility were unaffected by refresher training, suggesting the limits of histological dating have been reached.

Biopsy↗
PubMed2000

Cytologic and histologic diagnosis and significance of controversial squamous lesions of the uterine cervix.

The interpretation and precise classification of abnormal squamous cell changes in cervicovaginal smears (Pap tests) and tissue samples are challenging and controversial. The cytologic category atypical squamous cells of undetermined significance and the newly described squamous lesions atypical immature metaplasia, papillary immature metaplasia, and transitional cell metaplasia are representative. Their current status is reviewed, and future directions aimed at resolving some of the controversy and challenge are suggested.

Carcinoma in Situ↗
PubMed2000

Thin layer compared to direct smear in thyroid fine needle aspiration.

The efficacy of preparing thyroid fine needle aspirations (FNAs) by the thin layer as opposed to the direct smear method has not been evaluated sufficiently in a regional laboratory setting. At the Foothills Hospital (Calgary, Canada), the method of processing thyroid FNAs was changed from direct smear to thin layer in January 1996. The results of 327 patients who had direct smear from 1994 to 1995 were compared to 401 who had thin layer between 1996 and 1997. While there were no significant differences across a broad range of quality indicators, thin layer showed a trend towards a higher proportion of true benign diagnoses (31% vs 24%), a lower proportion of inadequate specimens (41% vs 50%) and, most importantly, a lower false negative rate (3% vs 9%). In conclusion, the changeover to thin layer did not compromise the interpretation of thyroid FNAs.

Adenoma↗
PubMed2000

Papnet-assisted, primary screening of cervico-vaginal smears.

PURPOSE: The Papnet system was initially designed for rescreening negative Pap tests but may also be an effective primary screener. METHODS: A set of 2,200 archival slides diagnosed by conventional, manual screening as 2,000 (90%) WNL, 47 (2.1%) carcinomas, 50 (2.3%), HSIL, 50 (2.3%) LSIL, and 53 (2.4%) ASCUS/AGUS were compared to the results of Papnet-assisted, primary screening. Following Papnet scanning, the digitized images were triaged and classified as abnormal or negative. All abnormals had a full manual screening, whereas negatives had a limited screening. Results by each screening method were compared and discordant cases were peer reviewed for a consensus result. Screening efficacy by each method was measured against a standard result composed of the concordant and consensus results. RESULTS: There were 101 concordant and 181 discordant abnormal results. The standard result for the slide set was 1,953 (88.9%) WNL, 87 (3.9%) ASCUS/AGUS, 52 (2.4%) LSIL, 62 (2.8%) HSIL, 39 (1.8%) carcinomas, and 5 (0.2%) unsatisfactory. Papnet versus manual sensitivity rates were 87.6% vs 72.3% at the ASCUS/AGUS threshold, 85.6% vs 82.4% at the LSIL threshold, and 89.1% vs 90.1% at the HSIL threshold. CONCLUSIONS: Papnet-assisted, primary screening equals conventional, manual screening in the detection of a wide range of cell abnormalities and is more effective in the detection of abnormalities at the lower end of the abnormal spectrum.

Adult↗
PubMed1999

Accuracy of Pap tests reported as CIN I.

Papanicolaou (Pap) tests reported as CIN I (cervical intraepithelial neoplasia, grade 1) may be subject to laboratory misclassification because of screening and interpretative errors. A peer-groupC consensus review was conducted to measure the misclassification rate of Pap tests reported as CIN I and to analyze the undercalled and overcalled tests for due cause. Four hundred and forty-nine Pap tests originally reported as CIN I were independently reviewed twice by a panel of four pathologists, and disagreements were resolved by consensus review. Results were based on the original screening for the first review and, following the removal of those markings, were based on a second, independent rescreening for the second review. A review result of low-grade squamous intraepithelial lesion (LSIL) and atypical squamous cells of undetermined significance (ASCUS) favoring LSIL was equated with the original CIN I result. Final classification was based on the second consensus review. Misclassified tests were categorized as screening or interpretative errors, based on a comparison of the review classifications. LSIL and ASCUS favoring LSIL were reported in 85.1% and 73.9% of the first and second reviews, respectively. In the final classification there were 362 (80.6%) LSIL and ASCUS-LSIL and 87 (19.4%) misclassifications: 31 (6.9%) undercalls and 56 (12.5%) overcalls. Screening error accounted for 35.5% of undercalled tests, and the remainder were interpretative errors, as were all those overcalled. In this study, Pap tests reported as CIN I were subject to misclassification because of a laboratory error in 19.4% of tests. Reductions in screening and interpretative errors were identified as mechanisms for improving accuracy. Diagn. Cytopathol. 1999;21:129-136.

Algorithms↗
PubMed1999

Malignant mesothelioma eight years after a diagnosis of atypical mesothelial hyperplasia.

The separation of mesothelial hyperplasia from early malignant mesothelioma remains one of the most difficult problems in histopathology. Inconclusive cases are termed "atypical mesothelial hyperplasia" and treated expectantly. A 49 year old male pipeline engineer was diagnosed as having atypical mesothelial hyperplasia in appendiceal serosa by the US-Canadian Mesothelioma Panel. Eight years later, he developed overtly malignant peritoneal and pleural mesothelioma. In hindsight, histological similarities between the diffuse malignant mesothelioma and the atypical mesothelial proliferation suggested malignancy from the outset. The most important of these features were the degree of mesothelial proliferation, micronodularity, architectural complexity, superficial invasion, uniform mild cytological atypia, and the absence of a clinical cause for a benign mesothelial proliferation. Ancillary investigations including immunohistochemistry were of no benefit in determining whether the atypical mesothelial hyperplasia was benign or malignant. Careful histological examination remains the mainstay of the diagnosis of early mesothelioma.

Appendiceal Neoplasms↗
PubMed1998

Predictors of co-incidental CIN II/III amongst a cohort of women with CIN I detected by a screening Pap test.

Approximately 20-40% of lesions interpreted by a screening Pap test as CIN I and subsequently examined by colposcopy include a co-incidental CIN II/III. Since the HPV profiles of CIN I and CIN II/III differ, HPV typing may predict these co-incidental higher grade lesions. Based on both the colposcopic impression and repeat Pap test, 537 women referred for examination of CIN I as classified by a screening Pap test were triaged into group A (</= CIN I) or group B (>/= CIN II). Clinical, demographic, reproductive, and risk factor data was collected by questionnaire and HPV typing of cervical scrapes was done by PCR. Group A included 342 (63.7%) women and group B 195 (36.3%). Group B women more frequently were current cigarette smokers (p<0.001) and had a high school or lesser level of education (p=0.04). HPV positivity amongst younger group B women (</= 21 years) and a history of current/occasional cigarette smoking in those 22 years and older were significant predictors of triaged, co-incidental CIN II/III (p<0.001). This age restriction will limit the adoption of HPV testing as an universal, adjunctive test for the identification of CIN II/III amongst CIN I lesions detected by a screening Pap test. A greater health advantage may be gained by increasing women's awareness of the risks, including that of cervical cancer associated with cigarette smoking.

Adult↗
PubMed1998

The natural history of CIN I lesions.

The published literature indicates 11% of CIN I lesions on average progress to a higher grade dysplasia and the remainder either regress or persist. Reliable markers of disease outcome are yet to be identified. A longitudinal study of 342 women referred for colposcopic examination of a CIN I detected by a screening Pap test, and classified by the colposcopic impression and Pap test at that exam as </= CIN 1 was designed to identify predictors of disease outcome. The cohort was comprised of 220 women who satisfactorily completed the study and whose disease was neither biopsied or treated at the initial examination. All had HPV DNA testing by PCR, and were followed with interval colposcopic examinations and repeat Pap tests for a limited time period. The initial HPV DNA status and a number of measured clinico-pathological and risk factor variables were analyzed to identify outcome predictors. All underwent a biopsy either at the conclusion of the study or because their disease was considered to have progressed during the follow up period. Biopsy confirmed progression to CIN II/III occurred in 41 (18.6%), persistence of CIN I/Condyloma in 41 (18.6%), and regression to <CIN I/Condyloma in 138 (62.7%). HPV DNA positivity and current, oral contraceptive use were the only independent predictors of progression when age at diagnosis, the number of follow up visits, and time to progression were controlled. Predictors of persistent and regressed disease were not identified. The study highlights a clinical role for HPV testing in the colposcopic management of CIN I lesions. Oral contraceptives may promote progression by regulating the oncogenic sequences of the HPV.

Adolescent↗
PubMed1997

Review of the screening history of Alberta women with invasive cervical cancer.

OBJECTIVE: To conduct a failure analysis of cervical cancer screening among women with invasive cervical cancer in Alberta. DESIGN: Descriptive study. Review of demographic, staging and treatment information from cancer registry records; generation of documented screening history from Alberta Health billing records and self-reported history from subjects who agreed to be interviewed; and comparison of findings in initial cytology reports with those from subsequent review by at least 2 pathologists of all cytology slides for each patient for the 5 years before diagnosis. Cases were assigned to 1 of 6 categories of identified screening failure. SETTING: Alberta. SUBJECTS: All women with diagnosis of invasive cervical cancer reported to a population-based provincial cancer registry from January 1990 to December 1991. OUTCOME MEASURES: Demographic, staging and treatment information; documented and self-reported screening histories; correlation of test results in initial cytology report with those generated from slide review; category of identified screening failure. RESULTS: Of the 246 women identified with invasive cancer of the cervix, 37 (15.0%) had stage IA disease; 195 (79.3%) had squamous-cell carcinoma, and 35 (14.2%) had adenocarcinoma. According to the categories of screening failure, 74 women (30.1%) had never been screened, 38 (15.4% had not been screened within 3 years before diagnosis, 42 (17.1%) had had a false-negative cytology result, and 20 (8.1%) had been managed outside of conventional protocols. Of the 23 women (9.3%) who had been screened appropriately and had true-negative results, 19 had smears that were considered technically limited. It was not possible to classify 49 (19.9%) of the cases. Agreement between the documented and the self-reported screening histories was exact for only 39 (36.1%) of the 108 women interviewed. CONCLUSIONS: Despite widespread use of opportunistic cervical screening, many women in Alberta are still not being screened adequately. In most cases women are being screened too infrequently or not at all. Self-reported screening histories are unreliable because many women may overestimate the number of smears. An organized approach to screening, as recommended by the National Workshop in Cervical Cancer Screening, may assist in reducing the incidence of invasive cervical cancer.

Adenocarcinoma↗
PubMed1997

Paired comparison of manual and automated Pap test screening using the PAPNET system.

A paired-comparison study of manual and automated (PAPNET) screenings of cervico-vaginal smears (Pap tests) was conducted to determine whether primary PAPNET screening was a reliable alternative to manual screening. A series of 5,037 consecutive Pap tests was first screened by the manual method. Next they were scanned by the PAPNET system, the DAT tapes were reviewed, and using a nonspecific triage protocol, abnormal tests were identified for limited, manual rescreening. False-negative rates (FNR) for each method were calculated and analyzed for due cause. By manual and PAPNET screening, respectively, there were 436 (8.6%) and 250 (4.9%) abnormal results. Manual screening missed 18 abnormals (5 SIL) and PAPNET 202 (7 SIL). The primary, manual screenings relating to the PAPNET false-negative tests were reviewed and revised to normal in 30. Based on the changes in the other 172 tests, cellular features ostensibly missed by the PAPNET system were listed to form part of a specific triage protocol, and were used to scrutinize the companion 172 DAT tapes: 150 tapes were abnormal. The manual FNR for an abnormal (SIL) result was 4% and (8.8%), respectively. Equivalent FNR pre- and postreviews for the PAPNET system were 44.6% (10.6%) and 5.2% (1.3%), respectively. This study discovered that the evaluation of some cell features in monitor-based, video images was the most important factor limiting the application of the PAPNET system as a primary screener. When governed by a specific triage protocol incorporating these features, primary PAPNET screening has the potential to equal the laboratory threshold of manual screening and be a better detector of SIL.

Automation↗
PubMed1997

The HPV determinants of CIN I.

Correlates of HPV amongst a cohort of women with a CIN I detected by a screening Pap test were investigated. Co-incident CIN II/III lesions were identified and their influence on the HPV status and HPV determinants of screening detected CIN I was assessed. Based on both the colposcopic impression and repeat Pap test, 537 women referred for examination of a Pap test classified as CIN I were triaged into two groups. Group A lesions were assessed as </= CIN I; n = 342 (63.7%) and group B as >/= CIN II; n = 195 (36.3%). Clinical, demographic, reproductive, and risk factor for cervical cancer correlates were collected. HPV typing of cervical scrapes collected at the colposcopic examination was done by PCR amplification using seven sets of type specific and one set of consensus primers. HPV positivity was identified in 47% of all scrapes; types 16/18 (28%), 31/33/35 (10%), 6/11 (2%), and unknown (7%). The HPV status of the cohort and group A were very similar. Group B had a slightly higher rate of HPV positivity (52%) due to an increase in types 16/18. Statistically significant correlates of HPV prevalence or type were not identified either for the entire group or both triage groups, however in each group, HPV positive women tended to be younger and to have more sexual partners. Co-incident CIN II/III spuriously increased the HPV prevalence rate of CIN I detected by a screening Pap test. The HPV appears to be sexually transmitted both in low and high grade lesions and explains why the HPV determinants of the entire cohort were unaffected by the co-incident CIN II/III.

Adolescent↗
PubMed1996

Human papillomaviruses in gynecological cancer.

Human papillomavirus-related anogenital neoplasia is an active area of basic and clinical research. The research topics are broad based, but mostly are focused on delineating the clinical utility of human papillomavirus testing, the natural history of human papillomavirus infections and associated premalignancies, characterization of the oncogenic role of human papillomavirus in sites other than the uterine cervix, and the mechanisms of human papillomavirus-associated carcinogenesis.

Female↗
PubMed1995

The human papillomavirus status of invasive cervical adenocarcinoma: a clinicopathological and outcome analysis.

Accumulating evidence highlights the human papillomavirus (HPV) as a risk factor for cervical adenocarcinoma. However, the part played by the HPV in predicting tumor outcome or the increasing frequency of cervical adenocarcinoma is incompletely studied. In a retrospective study the association between HPV status and the clinicopathological characteristics of 77 cases of cervical adenocarcinoma was investigated. The data were then analyzed for temporal differences in HPV status and to identify outcome predictors. Human papillomavirus status was determined by dot blot hybridization using probes for HPV 6, 11, 16, 18, 31, 33, and 35, followed by polymerase chain reaction amplification of the dot blot negative cases. Seven type-specific and consensus HPV primers were used. Human papillomavirus type 16, 18, or 33 was present in 53 (70%) cases. Human papillomavirus status did not correlate with disease outcome or any clinicopathological variable, except that tumors presenting in and after 1981 were more frequently HPV positive than those presenting before 1981 (P = .014). In a multivariate analysis only clinical stage at presentation was predictive of disease outcome. Because temporal differences in clinicopathological characteristics were not identified, the increasing frequency of cervical adenocarcinoma may relate to a more important oncogenic role for the HPV in tumors presenting after 1980.

Adenocarcinoma↗
PubMed1995

Uterine atypical polypoid adenomyoma and ovarian endometrioid carcinoma: metastatic disease or dual primaries?

Atypical polypoid adenomyoma (APA) is an uncommon uterine tumor that rarely metastasizes, although it closely resembles a well-differentiated endometrioid carcinoma. A 37-year-old woman with a history of pelvic endometriosis and oral contraceptive use developed an APA and later presented with bilateral ovarian endometrioid carcinomas. DNA ploidy analysis and human papilloma virus (HPV) typing of the APA and ovarian carcinomas were performed to characterize the primary or metastatic nature of the tumors. Both tumors were aneuploid. The APA had a DNA index of 1.53, compared with 1.19 for the ovarian carcinoma. The APA contained HPV 18, and the ovarian carcinoma a mixed infection of HPV 6, 11, 16, and 18, with types 6 and 11 predominating. These differences in DNA index and HPV type supported the autonomous nature of the APA and the ovarian carcinomas. The report affirms the benign outcome of APA, highlights its complication by a second malignancy, and suggests an etiological role for endometriosis, steroid hormones, and possibly the HPV in the formation of one or both tumors.

Adenomyoma↗