Management of patients with two consecutive ASC-US smears.

INTRODUCTION: To determine whether aggressive or expectative management of patients after two consecutive smears with atypical squamous cells of undetermined significance is preferable. To determine whether triage with high-risk human papillomavirus will identify all patients with cervical intraepithelial neoplasia grade 2 and 3. METHODS: 140 of 282 patients referred for colposcopy with two consecutive smears with atypical squamous cells of undetermined significance were only treated when abnormalities suggestive of high-grade cervical intraepithelial neoplasia were present at colposcopy. The other 142 patients underwent excision of all detected colposcopic abnormalities. Both groups were compared regarding the final cytological follow-up, the number of diathermy loop excisions, and the detection of cervical intraepithelial neoplasia. Retrospectively, the outcome of triage with high-risk human papillomavirus in the first group was investigated. RESULTS: There was no significant difference in final cytological follow-up between patients managed by expectative or by aggressive colposcopic management. Significantly less diathermy loop excisions (p < 0.001) are performed in case of expectative management. The sensitivity, specificity, negative- and positive predictive values of triage with high-risk human papillomavirus detection were comparable with those of colposcopy alone. CONCLUSIONS: Patients referred with two consecutive ASC-US smears may be followed with an expectative colposcopic management and cytological follow-up. Triage with high-risk human papillomavirus will reduce the number of referrals and colposcopies, but (cytological) follow-up remains necessary in all high-risk human papillomavirus negative patients as well.

[Wait-and-see policy versus loop excision after two consecutive Pap-2 cervical smears: over time less surgery and an equivalent outcome; no substantial contribution to be expected from the detection of high risk human papillomavirus]. / Expectatief beleid versus lisexcisies na 2 opeenvolgende Pap-2-uitstrijkjes: op termijn minder ingrepen en een gelijke uitkomst; geen wezenlijke bijdrage te verwachten van detectie van hoogrisico-humaanpapillomavirus.

OBJECTIVE: To determine the number interventions and outcomes in patients referred with two consecutive Pap 2 cervical smear results who were managed either by a wait-and-see policy or aggressively, and to determine whether triage with high-risk human papillomavirus (hr-HPV) detection, resulting in the referral of only hr-HPV positive patients, would lead to the detection of all patients with cervical intraepithelial neoplasia (CIN). DESIGN: Retrospective comparison and retrospective cohort study. METHOD: 282 patients referred in 1997/'99 with 2 consecutive Pap 2 cervical smears in the screening program were included. Patients referred to the UMC St Radboud Hospital (n = 140; mean age: 45 years) underwent a colposcopy during which only lesions suggestive for CIN 3 were treated. All other colposcopic lesions (CIN 2 or less) were not treated but followed prospectively. Patients referred to the Canisius Wilhelmina Hospital (CWZ) (n = 142; mean age: 44 years) underwent colposcopy during which all colposcopic lesions (including CIN 2 or less) were treated directly. The two groups were compared in terms of the final cytological follow-up, the number of loop excisions, and the number of patients with CIN. The mean follow up was 40 months. In the first group, the effect of triage using hr-HPV detection was also investigated retrospectively. RESULTS: With the wait-and-see approach, statistically significantly fewer diathermic loop excisions were done: 13 versus 124. After the follow-up period there was no statistically significant difference between the two groups in terms of the number of patients with persisting Pap 2: 16 (11%) versus 12 (8%). Triage with hr-HPV detection would identify all patients with CIN 3, 50% of the patients with CIN 2, and none of the patients with CIN 1; of the 48 hr-HPV-positive women, 1 had a CIN 3 lesion and 3 had a CIN 2 lesion; of the remaining 92 women, 2 had a CIN 1 lesion and 3 had a CIN 2 lesion. CONCLUSION: The wait-and-see approach led to fewer interventions, while the number of women with persisting Pap 2 smears was not higher than with the aggressive approach. Triage with hr-HPV may reduce the number of referrals and colposcopies, but follow-up remains necessary in all women regardless of hr-HPV status.

Clinical value of components of the plasminogen activation system in ovarian cyst fluid.

BACKGROUND: The aim of this study was to analyze the concentrations of different components of the plasminogen activation system in cyst fluid from malignant, borderline and benign ovarian tumors and to compare these results with clinicopathological characteristics (FIGO staging, histological grading, residual tumor, ascites, tumor recurrence and disease-free survival). MATERIALS AND METHODS: One hundred and seven cyst fluid samples were enrolled from 25 malignant, 12 borderline and 70 benign ovarian tumors. Determination of uPA, tPA, PAI-1, PAI-2, uPA:PAI-1 complex and tPA:PAI-1 complex was performed by specific double determinant ELISAs based on the concept described previously by Grebenschikov et al. With these ELISAs both complexes of the activators (uPA, tPA) with their inhibitor (PAI-1) can be measured as a separate component. RESULTS: Significant differences were found in median cyst fluid concentrations of uPA, PAI-1, uPA:PAI-1 and tPA:PAI-1 from malignant, borderline and benign ovarian tumors, with the highest levels in malignant ovarian tumors. Cystic endometriosis seems to be a special entity within the benign subclass. To achieve better discrimination between malignant and benign cases we introduced a new malignancy index: ([uPA:PAI-1]+[tPA:PAI-1])x [PAI-1]. The area under a Receiver Operating Characteristic (ROC) curve amounted to 0.80. Significantly higher concentrations were found in FIGO stages II-III-IV compared with stage I for uPA (p<0.05), tPA (p<0.05), uPA:PAI-1 (p<0.01) and tPA:PAI-1 (p<0.05). CONCLUSION: Concentrations of plasminogen activation system markers in cyst fluid from ovarian tumors are related to histological subtype. The most significant components are uPA, PAI-1 and the complexes uPA:PAI-1, tPA:PAI-1. The prognostic value of the components seems to be limited but might be important in detecting high-risk borderline or low stage patients.