Bias associated with delayed verification in test accuracy studies: accuracy of tests for endometrial hyperplasia may be much higher than we think!

BACKGROUND: To empirically evaluate bias in estimation of accuracy associated with delay in verification of diagnosis among studies evaluating tests for predicting endometrial hyperplasia. METHODS: Systematic reviews of all published research on accuracy of miniature endometrial biopsy and endometr ial ultrasonography for diagnosing endometrial hyperplasia identified 27 test accuracy studies (2,982 subjects). Of these, 16 had immediate histological verification of diagnosis while 11 had verification delayed > 24 hrs after testing. The effect of delay in verification of diagnosis on estimates of accuracy was evaluated using meta-regression with diagnostic odds ratio (dOR) as the accuracy measure. This analysis was adjusted for study quality and type of test (miniature endometrial biopsy or endometrial ultrasound). RESULTS: Compared to studies with immediate verification of diagnosis (dOR 67.2, 95% CI 21.7–208.8), those with delayed verification (dOR 16.2, 95% CI 8.6–30.5) underestimated the diagnostic accuracy by 74% (95% CI 7%–99%; P value = 0.048). CONCLUSION: Among studies of miniature endometrial biopsy and endometrial ultrasound, diagnostic accuracy is considerably underestimated if there is a delay in histological verification of diagnosis

Oral isotretinoin in the treatment of recalcitrant condylomata acuminata of the cervix: a randomised placebo controlled trial

Objectives: To investigate the efficacy and safety of low dose oral isotretinoin in recalcitrant condylomata acuminata (RCA) of the cervix. Methods: Double blind placebo controlled clinical trial. 60 women, aged 21–43 years, with RCA of the cervix, refractory to at least one conventional therapy, were randomly assigned to receive either isotretinoin, 0.5 mg/kg daily for 12 weeks (group 1), or placebo (group 2). Results: Of the 28 evaluable group 1 patients, nine (32.1%) responded to the treatment completely, 11 (39.2%) responded partially, and eight (28.5%) did not respond. Of the 25 group 2 patients, no one responded to the treatment completely, two (8%) responded partially, and 23 (92%) did not respond. The therapeutic difference between patients receiving active and placebo therapy was statistically significant (χ(2) = 19.35, p<0.001). Only one (11.1%) of the complete responders experienced recurrence during the 12 month follow up. Side effects were generally mild and resolved upon completion of therapy. Conclusions: Compared to placebo, low dose oral isotretinoin showed considerable efficacy with insignificant and reversible side effects and a low recurrence rate. Isotretinoin may represent an efficacious and safe alternative systemic form of therapy for RCA of the cervix

THE PREDICTIVE VALUE OF A NONSTRESS TEST TAKEN 24 H BEFORE DELIVERY IN HIGH-RISK PREGNANCIES

OBJECTIVES: A series of 180 cases of high risk pregnancies were studied in order to assess ifa nonstress test taken 24 h before delivery is of any prognostic significance. METHODS. To assess the predictability of the NST (reactive or nonreactive) in terms of fetal outcome, the following variables were taken into consideration. fetal distress during labor, low Apgar score (&lt; 7) and perinatal mortality rate. RESULTS: A reactive test was found to be a good predictor of the healthy fetus (negative predictive value = 91.2%). Also, specificity of the test was found to be 85.4%. CONCLUSIONS: The nonreactive test could identify a population at;risk but it was not helpful as a ‘stand alone’ modality in decision making, because of the low sensitivity and positive predictive value rates (40.9% and 28.1%, respectively)

Comparative p16(IKN4A) Expression in Laryngeal Carcinoma and Cervical Cancer Precursors: A Real-time Grid-based Immunocytochemistry Analysis

Background/Aim: p16 (gene locus: 9p21) tumor suppressor gene is considered an important biomarker for the progression and prognosis in a variety of malignancies and pre-cancerous lesions, including high-risk (HR-) human papilloma virus (HPV)-mediated squamous intraepithelial lesions (SILs), based on cytological and the corresponding cervical intraepithelial neoplasia (CIN) histopathological categorization. p16 acts as a cyclin-dependent kinase-4 inhibitor negatively regulating the cell cycle. In persistent HPV infection, E7 oncogenic protein binds retinoblastoma protein leading to its proteolytic transformation, also triggering E2F dissociation, which increases DNA transcription and progression to S phase. This mechanism promotes aberrant p16 over-expression. Our aim was to comparatively analyze p16 protein expression patterns in laryngeal squamous cell carcinomas (LSCC) and also in SILs. Materials and Methods: Fifty (n=50) primary LSCCs tissues all non-HPV-dependent, and a set of 50 liquid-based SILs, were analyzed by immunohistochemistry and immunocytochemistry, respectively. Concerning the screening process in cytological slides, a novel real-time reference and calibration grid platform was implemented and employed. Results: Decreased protein expression was observed in 34/50 (68%) tissues regarding LSCCs. Overall p16 expression was associated to smoking status of the patients (p=0.001), and also with the p-stage of the examined malignancies (p=0.033). A strong statistical significance was assessed correlating LSIL/HSIL cases with a progressive p16 over expression (p=0.001), also reflecting a higher CIN diagnosis (p=0.001). Conclusion: p16 down- regulation is a frequent genetic event in LSCCs, which is associated with advanced disease. In contrast to this, p16 over- expression triggered by a specific molecular mechanism shows a strong relationship with a progressively aggressive phenotype due to upgraded SIL/CIN cervical categorization. The first described application of the grid platform demonstrated a considerable improvement in the immunocytochemistry slide screening process enhancing the diagnostic reliability

The classification of gestational trophoblastic disease: A critical review

International Journal of Gynecology and Obstetrics60SUPPL.1IJGO