ObjectiveThe malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease.MethodsFour hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsOf the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality.ConclusionLaser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary.

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In rat pancreatic islets the effects of diamide, which has been shown to decrease islet levels of reduced glutathione (GSH), and of exogenous GSH were investigated on cyclic AMP as increased by glucose, p-chloromercuribenzoate, and aminophylline. In addition the effect of diamide on islet ATP level, low Km and high Km phosphodiesterases was studied. Diamide (0.1 mM) inhibited the increase of cyclic AMP (cAMP) in response to glucose (16.7 mM), and p-chloro-mercuribenzoate (1 mM) in the presence of 5.6 mM glucose. No inhibitory effect of diamide could be demonstrated when cAMP was raised by 10 mM aminophylline in the presence of 5.6 mM glucose. The glucose (27.7 mM) stimulated increase of cAMP was further augmented by GSH (0.4 mM) whereas GSH in the presence of 5.6 mM glucose had no such effect. Diamide neither affected islet high Km nor low Km cAMP-phosphodiesterases. Diamide (0.1 mM) as used in this study did not affect islet AMP levels. A concentration dependent decrease of ATP was observed, however, with higher concentrations of diamide (0.25, 0.5 and 1.0 mM). It is suggested that the accumulation of islet cAMP in response to glucose and para-chloromercuribenzoate depends on the redox state of islet thiols. Since thiol oxidant diamide neither affected cAMP-phosphodiesterase activities nor inhibited aminophylline induced accumulation of cAMP in the presence of low glucose the possibility is raised that in pancreatic islets the formation of cAMP rather than its degradation depends on the redox state of islet thiols.

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