Intra-operative frozen section analysis for suspected early-stage ovarian cancer: 11 years of Gateshead Cancer Centre experience.

OBJECTIVE: In centres in which intra-operative frozen section (FS) analysis is not performed, 'apparent' early-stage ovarian cancer diagnosed after surgery on paraffin section may require further restaging laparotomy or adjuvant chemotherapy. Previous studies on FS analysis have reported high sensitivity, specificity and overall accuracy. The objective of this article is to present the largest published dataset on the accuracy of FS analysis over an 11-year period from a single institution. DESIGN: Diagnostic test accuracy. SETTING: Northern Gynaecological Oncology Centre and Department of Cellular Pathology, Gateshead, UK. POPULATION: 1439 intra-operative FS analyses performed between January 2000 and December 2010 for suspected ovarian cancer. METHODS: Prospectively collected data on FS analysis were compared with gold standard paraffin section. MAIN OUTCOME MEASURES: Sensitivity, specificity, likelihood ratios and post-test probability. RESULTS: The overall sensitivity and specificity of FS analysis were 91.2% and 98.6%, respectively. Positive and negative likelihood ratios were 64.7% and 0.09%, respectively. The pre-test probability of an ovarian tumour being borderline or malignant was 45.8%. When FS analysis was reported to be positive, the post-test probability increased to 98% (confidence interval, 97-99%). Conversely, when FS analysis was reported to be negative, the post-test probability decreased to 7% (confidence interval, 6-9%). The majority of false test results were either borderline tumours or of mucinous differentiation. CONCLUSIONS: Intra-operative FS analysis has excellent diagnostic test accuracy and assists gynaecological oncologists to perform the appropriate surgery in 95% of cases, thereby preventing the morbidity of surgical staging in benign cases and the morbidity of restaging procedures or chemotherapy in early-stage malignant tumours.

Borderline nuclear change, high-grade dyskaryosis not excluded: current concepts and impact on clinical practice.

OBJECTIVE: Borderline nuclear change, high-grade dyskaryosis not excluded (B/HG) is a subcategory of the borderline category recommended by the British Society for Clinical Cytology as warranting direct referral to colposcopy. This subcategory is equivalent to the Bethesda category of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). The purpose of this study was to determine the validity and accuracy of using B/HG to identify potential cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+). METHODS: Data were collected from the hospital pathology database for borderline, B/HG and high-grade cytology (moderate dyskaryosis and above), and their respective histological and colposcopic outcomes. SPSS was used for data analysis. RESULTS: Of the 84,799 total cytology samples screened between July 2006 and December 2009, 5225 (6.1%) were reported as borderline, 309 (0.4%) as B/HG and 1222 (1.4%) as high-grade cytology. Thus, B/HG comprised 5.9% of the overall borderline category, in keeping with national guidelines (<10%). CIN2+ was confirmed in 86.6% of high-grade, 40.8% of B/HG and 3.0% of borderline cytology. Of 309 women reported with B/HG cytology, 239 had colposcopy. Colposcopic appearances showed a positive predictive value (PPV) of 71.8% for detecting CIN2+ and a negative predictive value of 60.7%. CONCLUSIONS: The B/HG category was associated with a significantly higher incidence of CIN2+ compared with borderline cytology as a whole. This refining performance justifies its existence. Colposcopic appearances had a high PPV for detecting CIN2+. Therefore, colposcopy is recommended in patients with B/HG cytology and treatment should be offered if high-grade colposcopic changes are seen.

Use of the monoclonal antibody DAKO-ERbeta (8D5-1) to measure oestrogen receptor beta in breast cancer cells.

BACKGROUND: Oestrogen receptor beta (ERbeta) is highly homologous with the classical ER (known now as ERalpha). The exact role of ERbeta in breast cancer and its contribution in influencing patient response to endocrine therapy remains unclear. The aim of this study was to develop and evaluate a flow cytometric method for the detection of ERbeta in breast cancer cells using the DAKO monoclonal anti-ERbeta 8D5-1 antibody. METHODS: MCF7 cells were used as a positive control and U937 as a negative control for titration of the antibody. Cell lines and tumour samples were fixed with 1% paraformaldehyde and permeabilised with 0.5% saponin prior to flow cytometric analysis. RESULTS: A ten fold difference in expression of ERbeta within the different breast cell lines studied was found. Confirmation of antibody specificity against ERbeta protein by Western blot analysis detected a single band at approximately 65kDa. ERbeta immunopositive nuclei were identified in MCF7 cells by immunohistochemistry. CONCLUSIONS: DAKO ERbeta 8D5-1 antibody is specific for ERbeta protein and does not cross react with ERalpha protein. Using this antibody, ERbeta can be detected and accurately quantified in cell lines and solid breast tumours by flow cytometry.

The feasibility of a one-stop colposcopy clinic in the management of women with low grade smear abnormalities: a prospective study.

OBJECTIVES: To assess the feasibility of a one-stop colposcopy clinic for the management of women with low-grade smear abnormalities. Secondly, to determine whether the approach of immediate information of biopsy results combined with treatment if indicated helps to reduce patient anxiety and improve overall patient satisfaction with the colposcopy process. DESIGN: Prospective study following the introduction of a "one-stop" process for the management of women with low grade smear abnormalities. SUBJECTS: First 118 women managed in a "one-stop" clinic during an 8-month period. METHODS: Assessment of patient anxiety via self-completed questionnaires and comparison of anxiety scores with a control group managed via a standard clinic. RESULTS: The median waiting time for results in the one-stop clinic was 120 min (range: 100-165). All women in both groups felt anxious at the time of the clinic visit. However, after 1 week the majority of patients managed via the one-stop process felt slight anxiety only (P=0.0001) as opposed to those patients in the control group who remained anxious (P=NS). In addition, all women said they would prefer the one-stop approach for further smear abnormalities if a further colposcopic examination was warranted. CONCLUSION: A one-stop colposcopy clinic is feasible for the management of women with low-grade smear abnormalities. In addition, it delivers a quality service, optimises patient management, reduces anxiety and is the patient's choice.

Diagnosis of molar pregnancy and persistent trophoblastic disease by flow cytometry.

Histopathological assessment and flow cytometric analyses were carried out on 32 placentas (representative of each trimester) and 88 molar pregnancies. Three first trimester placentas were triploid, and the remaining 29 placentas were diploid. Of the 88 cases originally diagnosed as molar pregnancies, 26 were triploid (two complete moles, 20 partial moles, and four hydropic abortions); 59 were diploid (46 complete moles, 10 partial moles, three hydropic abortions); one was tetraploid (partial mole); and two were DNA aneuploid (one partial mole, one complete mole). A significantly increased hyperdiploid fraction (a measure of cell proliferation) was detected in diploid complete moles (p less than 0.0001) and cases of persistent trophoblastic disease (p less than 0.001) when compared with diploid placentas and diploid partial moles. All seven cases of established persistent trophoblastic disease, for which follow up was available, were diploid and showed high hyperdiploid fractions within the range for diploid complete moles. These findings suggest that flow cytometric DNA measurements may be an important aid in the diagnosis of molar pregnancy. The high degree of cell proliferation found in this study may explain the premalignant potential of complete hydatidiform moles.

Bioavailability of aspirin in the presence of dextropropoxyphene/paracetamol combination.

The effect of 2 doses of a combination analgesic preparation (each dose containing 65 mg dextropropoxyphene hydrochloride and 650 mg paracetamol) upon plasma salicylate concentration after a single dose of soluble aspirin (1.2 g) or enteric-coated aspirin (1.2 g) was examined in 6 normal volunteers and compared with the effect of placebo. The dextropropoxyphene/paracetamol caused no reduction in the plasma salicylate level after absorption of soluble aspirin compared with placebo and, although a reduction in plasma salicylate was seen after enteric-coated aspirin in a single subject, this may reflect erratic absorption rather than a drug interaction.