Monique Bertrand

Cadherin switching in ovarian cancer progression.

The roles of the cadherins in the progression of ovarian cancer to the late stages of the disease state when malignant cells have disseminated within the peritoneal cavity remain poorly understood. In view of these observations, we have undertaken a comprehensive survey of the cadherin subtypes present in normal ovarian surface epithelium and peritoneum and in the tumors and peritoneal effusions of women diagnosed with Stage I or Stage II primary ovarian cancer using a degenerate cloning strategy for sequences highly conserved among this family of cell adhesion molecules. On the basis of the nucleotide sequences of the resultant PCR products, multiple cadherin subtypes (E‐, N‐, P‐cadherin, and cadherin‐4, ‐6, and ‐11) were found to be present in these normal and malignant tissues and cells. P‐cadherin was determined to be the predominant cadherin subtype in normal peritoneum, peritoneal effusions and Stage II tumor masses. An increase in P‐cadherin mRNA and protein expression levels in ovarian tumor masses with progression to later stages of the disease state was confirmed by Northern and Western blot analysis, respectively. In addition, we have determined that the cadherin‐associated protein, known as β‐catenin, is expressed in normal peritoneum, ovarian tumors and malignant cell effusions obtained from women with Stage I or Stage II cancer. Immunoprecipitation studies demonstrated that P‐cadherin was capable of interacting with β‐catenin in these normal and malignant tissues and cells. Collectively, these findings suggest that the regulated expression of P‐cadherin/β‐catenin complexes in ovarian tumor cells may represent a key step in disease progression.

Basal cell carcinoma of the vulva: Clinical features and treatment results in 28 patients

Objective To review our experience and that in the recent literature regarding basal cell carcinoma of the vulva to see whether current management guidelines are appropriate. Methods Twenty-eight women with basal cell carcinoma of the vulva were seen over 25 years at the BC Cancer Agency. The clinical-pathologic features were tabulated and the outcome was analyzed. Results The mean age was 74 years, and almost two-thirds were over the age of 70 at diagnosis. Patients typically presented with an irritation or soreness, with a symptom duration ranging from a few months to several years. Most lesions were confined to the anterior half of the vulva, and 23 of the 28 patients had T1 lesions. Wide local excision was the treatment method used most commonly. Only one patient was known to have died from disease metastasis. Ten women had other basal cell carcinomas, either before or after the diagnosis of their vulvar lesions, and in ten patients 11 other malignancies were diagnosed. Conclusion Basal cell carcinoma of the vulva is an extremely uncommon tumor that rarely metastasizes or spreads. Primary treatment should consist of wide local excision and continued follow-up.

Colposcopic management of abnormal cervical cytology and histology.

OBJECTIVE To provide a guideline for managing abnormal cytology results after screening for cervical cancer, to clarify the appropriate algorithms for follow-up after treatment, and to promote the best possible care for women while ensuring efficient use of available resources. OUTCOMES Women with abnormal cytology are at risk of developing cervical cancer; appropriate triage and treatment will reduce this risk. This guideline will facilitate implementation of common standards across Canada, moving away from the current trend of individual guidelines in each province and territory. EVIDENCE Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in October 2008 using appropriate controlled vocabulary (e.g., colposcopy, cervical dysplasia) and key words (e.g., colposcopy management, CIN, AGC, cervical dysplasia, LEEP, LLETZ, HPV testing, cervical dysplasia triage). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to July 2012. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, and national and international medical specialty societies. Expert opinion from published peer-reviewed literature and evidence from clinical trials is summarized. Consensus opinion is outlined when evidence is insufficient. VALUES The quality of the evidence is rated using the criteria described by the Canadian Task Force on Preventive Health Care (Table 1). VALIDATION This guideline has been reviewed for accuracy from content experts in cytology, pathology, and cervical screening programs. Guideline content was also compared with similar documents from other organizations including the American Society for Colposcopy and Cervical Pathology, the British Society for Colposcopy and Cervical Pathology, and the European Cancer Network.

Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia: Testing a device as an adjunct to colposcopy

Testing emerging technologies involves the evaluation of biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost‐effectiveness. The objective of this study was to select an effective classification algorithm for optical spectroscopy as an adjunct to colposcopy and obtain preliminary estimates of its accuracy for the detection of CIN 2 or worse. We recruited 1,000 patients from screening and prevention clinics and 850 patients from colposcopy clinics at two comprehensive cancer centers and a community hospital. Optical spectroscopy was performed, and 4,864 biopsies were obtained from the sites measured, including abnormal and normal colposcopic areas. The gold standard was the histologic report of biopsies, read 2 to 3 times by histopathologists blinded to the cytologic, histopathologic, and spectroscopic results. We calculated sensitivities, specificities, receiver operating characteristic (ROC) curves, and areas under the ROC curves. We identified a cutpoint for an algorithm based on optical spectroscopy that yielded an estimated sensitivity of 1.00 [95% confidence interval (CI) = 0.92–1.00] and an estimated specificity of 0.71 [95% CI = 0.62–0.79] in a combined screening and diagnostic population. The positive and negative predictive values were 0.58 and 1.00, respectively. The area under the ROC curve was 0.85 (95% CI = 0.81–0.89). The per‐patient and per‐site performance were similar in the diagnostic and poorer in the screening settings. Like colposcopy, the device performs best in a diagnostic population. Alternative statistical approaches demonstrate that the analysis is robust and that spectroscopy works as well as or slightly better than colposcopy for the detection of CIN 2 to cancer.

The quality of community Colposcopic practice

OBJECTIVE: To estimate the quality of community colposcopic practice in British Columbia through an assessment of the degree of correlation between colposcopy, cytology, and histology. METHOD: We reviewed all new-patient colposcopies in British Columbia during 2001 by 37 gynecologists in 24 hospital-based clinics. RESULTS: Colposcopic impression closely mirrored the referral cytology diagnosis in 89.8% of cases. As with cytology-biopsy comparisons, discordant cases were more likely to be overestimates of disease rather than underestimates, 18.8% versus 1.8%. Overestimates were usually biopsy sampling errors rather than false positive cytology. The overall correlation between cytology and biopsy was considered satisfactory in 79.4% of cases. Satisfactory agreement between the colposcopic diagnosis and accompanying biopsies occurred in 86.8% of patients. Five colposcopists had performance scores below this standard. Colposcopy with a sensitivity of 90.3% and a specificity of 57.3% as practiced in this provincial program would appear to be of a satisfactory level. The rate of intraepithelial or invasive disease increased from 40.6% in patients with low-grade squamous intraepithelial changes to 91.9% in patients with suspicious or malignant cytology. The value of the colposcopic impression to identify disease correlated best with the higher the grade of disease predicted (64.6% to 92.6%). CONCLUSION: A measure of the colposcopic proficiency in the community can be estimated by comparing the level of agreement between the presenting cytology, colposcopic impression, and corresponding directed biopsies. The results of this study would indicate that 5 individuals had practice standards that were below average. An integrated cytology-colposcopy program facilitates the assessment and identification of below-average practice standards in a community. LEVEL OF EVIDENCE: III

Costs of colposcopy services and their impact on the incidence and mortality rate of cervical cancer in Canada.

Objective Organized cervical cancer screening services consisting of conventional Papanicolaou cervical smears, colposcopy, and related treatment modalities are readily available in all provinces. The purpose of this report was to study the impact of colposcopy usage and costs on cervical cancer incidence and mortality rates in several Canadian provinces. Knowledge of such information is essential before newer technology such as liquid-based cytology and human papillomavirus testing is introduced or replaces the traditional systems used. Materials and Methods The Ministries of Health of five provinces were contacted and asked to furnish information on the number of colposcopic services and fee-for-service costs for these and for cryosurgery, carbon dioxide laser vaporization, loop electrosurgical excisions, and cold-knife conizations for the year 2000. Canadian Cancer Society estimates of incidence and mortality rates for cervical cancer were also obtained. Results All provinces had similar incidence and mortality rates for cervical cancer; however, the number of colposcopic services on a per-capita basis varied substantially, with Manitoba and Ontario having rates that were approximately two or three times higher. Fee-for-service payments for colposcopy were similar in the Provinces studied but unit costs for surgical treatment services were highest in Ontario and British Columbia. Conclusions Although both the incidence and mortality rates for cervical cancer in Canada fell dramatically after the Walton Report in 1976, these rates have plateaued over the past decade despite widespread availability of colposcopy and related ambulatory treatment services. Higher rates of colposcopy usage do not seem to result in lower incidence rates for this disease. Unit costs for colposcopy are similar among the provinces reviewed, but substantial difference exists for certain treatment services. Additional studies are recommended before the widespread introduction or replacement of existing methods with newer, more costly techniques.

The optimum organization for the delivery of colposcopy service in Ontario: a systematic review.

Objective: To determine the optimum organization for colposcopy service delivery in Ontario, Canada. Methods: A multidisciplinary expert panel was convened to develop a systematic review to inform organizational guidelines. MEDLINE, EMBASE, CINAHL, HealthSTAR, and the Cochrane Library databases were searched from 1996 to February 2006 for articles that reported guidance or outcomes relating to improved outcomes in colposcopy training, qualifications, accreditation, maintenance of competency, the delivery of colposcopy, reducing default from colposcopy clinics, and/or strategies to improve patient satisfaction or comfort. In addition, an environmental scan identified unpublished documents related to the delivery of colposcopy services. Results: Sixteen guidance documents related to the delivery of colposcopy services were identified; 5 from the published literature and 11 from the environmental scan. These documents were used by the panel to inform the systematic review and companion guidelines. Conclusions: Overall, the Ontario Colposcopy Guidelines Development Group believes that the benefits associated with the implementation of colposcopy recommendations in Ontario will result in greater organization of care and improved patient outcomes. In addition, the group anticipates that these recommendations will provide useful guidance to regional planning authorities, hospital administrators, and Cancer Care Ontario, as well as colposcopists and other practitioners, in the planning of integrated regional and provincial cancer screening services.

Urachal abscess and infected bladder diverticulum

Summary: Urachal abscess is an uncommon condition with protean features and often presents a diagnostic challenge to clinicians. This case report describes a 41‐year‐old woman with severe multiple sclerosis who was referred to a gynaecological oncology service with the presumed diagnosis of advanced ovarian cancer. A diagnosis of urachal abscess and infected bladder diverticulum was made by a combination of imaging modalities and a percutaneous biopsy. It is important to be aware of this entity, as the presentation varies widely and when diagnosed early the condition may be treated appropriately by relatively minor surgical intervention.

Prise en charge colposcopique des résultats cytologiques et histologiques anormaux en ce qui concerne le col utérin

Resume Objectif Fournir une directive clinique traitant de la prise en charge des resultats cytologiques anormaux issus du depistage du cancer du col uterin, clarifier les algorithmes appropries aux fins du suivi a la suite du traitement et promouvoir l’offre des meilleurs soins possibles aux femmes tout en assurant une utilisation efficace des ressources disponibles. Issues Les femmes qui obtiennent des resultats cytologiques anormaux sont exposees a un risque de voir apparaitre un cancer du col uterin; la mise en œuvre d’un triage et d’un traitement appropries attenuera ce risque. La presente directive clinique facilitera la mise en œuvre de normes communes a la grandeur du Canada, et ce, en vue de contrer la tendance actuelle qui veut que chaque province et territoire formule ses propres lignes directrices. Resultats La litterature publiee a ete recuperee par l’intermediaire de recherches menees dans PubMed ou Medline, CINAHL et The Cochrane Library en octobre 2008 au moyen d’un vocabulaire controle (p. ex. « colposcopy », « cervical dysplasia ») et de mots cles (p. ex. « colposcopy management », « CIN », « AGC », « cervical dysplasia », « LEEP », « LLETZ », « HPV testing », « cervical dysplasia triage ») appropries. Les resultats ont ete restreints aux analyses systematiques, aux essais comparatifs randomises / essais cliniques comparatifs et aux etudes observationnelles. Aucune restriction n’a ete appliquee en matiere de date ou de langue. Les recherches ont ete mises a jour de facon reguliere et integrees a la directive clinique jusqu’en juillet 2012. La litterature grise (non publiee) a ete identifiee par l’intermediaire de recherches menees dans les sites Web d’organismes s’interessant a l’evaluation des technologies dans le domaine de la sante et d’organismes connexes, dans des collections de directives cliniques, dans des registres d’essais cliniques et aupres de societes de specialite medicale nationales et internationales. Les opinions de specialistes issues de la litterature publiee soumise a l’examen collegial et les donnees issues d’essais cliniques sont resumees. Une opinion de consensus est presentee lorsque les donnees sont insuffisantes. Valeurs La qualite des resultats est evaluee au moyen des criteres decrits par le Groupe d’etude canadien sur les soins de sante preventifs (Tableau). Validation La precision de la presente directive clinique a ete analysee par des specialistes œuvrant dans les domaines de la cytologie, de la pathologie et du depistage cervical. Le contenu de la presente directive clinique a egalement ete compare a celui de documents similaires issus d’autres organisations, dont l’ American Society for Colposcopy and Cervical Pathology , la British Society for Colposcopy and Cervical Pathology et l’ European Cancer Network .

An analysis of 84,244 patients from the British colombia cytology-colposcopy Program

OBJECTIVE To determine the diagnostic correlation between referral cytology, initial biopsies and colposcopic impression in patients assessed in a provincial cytology screening program. METHODS A retrospective review of the computerized cytology screening database for British Columbia (BC), to identify all patients having their first colposcopy between 1986 and 2000 in 24 participating clinics constituted the study population. 84244 patient records were identified for analysis. Colposcopies were performed mainly by 37 general gynecologists as part of a province-wide colposcopy program. Correlation of cytology, colposcopic impression and directed biopsies was performed. RESULTS The colposcopic impression correlated with the referral cytology within one degree in over 90% of cases. Colposcopists felt cytology underestimated disease in 1.5% and overestimated disease in 8.3%. Cytology-histology correlation within one degree occurred in 82%. Cytology underestimated the result of the biopsies in 2.3% and appeared to overestimate disease in 16.1% of patients. Patients with HSIL cytology had corresponding lesions in 77%, with a further 4.9% having LSIL disease. The predictive accuracy of colposcopy increased with advancing severity of disease expected. As the degree of cytological abnormality worsened, the predictive accuracy of colposcopic diagnosis increased. CONCLUSIONS Both cytology and colposcopy have high sensitivity but low to moderate specificity. Colposcopy is most accurate in identifying high-grade diseases. Colposcopic impression correlates closely with the cytology diagnosis and combining the two produces optimum results.