Surgical treatments for vulvar and vaginal dysplasia: a randomized controlled trial. Topical imiquimod can reverse vulvar intraepithelial neoplasia: a randomised, double-blinded study. One-Session Management of Cervical Intraepithelial Neoplasia: A Solution for Developing Countries. A Prospective, Randomized Trial of LEEP versus Laser Excisional Conization A phase II randomized controlled trial of a novel male contraception, an intra-vas device. Gynaecologic surgery from uncertainty to science: evolution of randomized control trials. Enhancement of regression of cervical intraepithelial neoplasia II (moderate dysplasia) with topically applied all-trans-retinoic acid: a randomized trial. Outpatient excisional management of cervical intraepithelial neoplasia. A prospective, randomized comparison between loop diathermy excision and laser excisional conization. A randomized phase II trial of indole-3-carbinol in the treatment of vulvar intraepithelial neoplasia. Laparoscopic Burch colposuspension: a randomized controlled trial comparing two transperitoneal surgical techniques.
To compare pain, adverse effects and recurrence of dysplasia in patients with vaginal intraepithelial neoplasia or vulvar intraepithelial neoplasia prospectively treated by carbon dioxide laser or ultrasonic surgical aspiration.
                Patients were randomly assigned to receive treatment by laser or ultrasonic surgical aspiration from 2000-2005. Preoperative biopsy was done to confirm presence of dysplasia. Patients completed a visual analog scale regarding pain and were evaluated at 2-4 weeks to assess scarring, wound healing, and adverse effects. Patients returned every 3 months for 1 year for pelvic examination and cytology to assess recurrence. Follow-up colposcopy and biopsy were used at the discretion of the treating physician. Student t test, chi2, analysis of variance and multiple logistic regression were used for analysis.
                One hundred ten patients were randomly assigned. Ninety-six (87.3%) patients completed 1 year follow-up. Mean age of patients was 48.5 years. Mean visual analog scale score was significantly lower in patients treated by ultrasonic surgical aspiration (20.7 compared with 35.1; P=.032). For patients with vulvar lesions, there was less scarring with ultrasonic surgical aspiration (P<.01). Recurrence overall was 25% and was similar for ultrasonic surgical aspiration compared with laser (relative risk 0.96, 95% confidence interval 0.64-1.50, number needed to treat 95.6). Recurrence was associated with younger age (P<.01).
                Patients treated with ultrasonic surgical aspiration for vulvar and vaginal dysplasia reported less postoperative pain. Vulvar scarring was more common in patients treated by the laser. There was no difference in recurrence of dysplasia during a 1-year follow-up period between the two surgical modalities.
                ClinicalTrials.gov, www.clinicaltrials.gov, NCT00394758
                I. To investigate the effect of topical imiquimod in patients with vulvar intraepithelial neoplasia (VIN).
                We used a prospective, randomised, double-blinded, placebo-controlled study. Women with biopsy verified, visible VIN2 or VIN3, in a biopsy not older than 2 months were considered.
                Thirty-two patients were included, one was excluded before treatment. Twenty-one received active treatment, 10 received placebo. Seventeen (81%) in the treatment group showed complete response, two (10%) partial response and none responded in the placebo-group when evaluated by a biopsy 2 months after a treatment period of 16 weeks. Fourteen of 21 patients (67%) in the treatment group had to reduce the number of applications due to local side-effects.
                The topical treatment with imiquimod 5% was shown in this setting to be very efficient. Local side effects were a common feature, but tolerable after dose reduction. Long-term results are not known, but a planned cohort study of this population will show the rate of recurrences. Six hundred thirty-nine patients with CIN on referral Pap were evaluated cytocolposcopically at the first visit and decided whether to be treated the same day or not. One hundred ninety-two patients (30%) were considered negative. Follow-up evidenced later appearance of CIN in five of them. One hundred fifty-three (24%) were candidates for delayed treatment due to conditions contraindicating same-day treatment. Two hundred ninety-four patients (46%) were randomly allocated in LEEP (149) or excisional laser (145) arms, and treated the same day under local anesthesia. Both arms were comparable. There were three microinvasive carcinomas diagnosed in the surgical specimen. LEEP was faster and produced less bleeding than laser, although required a mean of four slices to remove the lesion. Arterial hypertension after anesthetic infiltration was detected in 26% of cases. Two intraoperative and two delayed bleeders required surgery. The size of lesion and surgical defect were larger than those reported in the literature. Margins were involved in 8 patients (2.7%). Only 4.7% (7/149) of patients randomized to LEEP and 3.4% (5/145) with excisional laser had persistent or recurrent CIN on follow-up. Factors predisposing to failure included depth of surgical defect, grade of lesion, and operator's expertise. With this approach, 69% of patients referred for cytology of CIN were adequately managed in the first visit, which contrasts to classical management that reaches the state of treatment in 30% of patients. LEEP appears to be faster, less costly, and requires less expertise. Its use in conjunction with adequate screening is recommended for developing countries. The aim of this study was to introduce a novel male contraceptive method, an intra-vas device (IVD), and to assess the efficacy, safety and satisfaction of recipients compared with no-scalpel vasectomy (NSV). A phase II randomized controlled trial was conducted in China in 2003. Two hundred and eighty-eight male subjects seeking vasectomy were randomly assigned to the IVD or NSV group. Follow up included a telephone questionnaire on the 14th postoperative day and visits at the third and 12th postoperative months. The follow-up rates at the three time points were 100%, 100% and 96.5% respectively. There was no technical failure in any subject. The surgical conditions were similar in both groups, but the IVD group experienced an additional 5 min of operative time (p<0.001). The IVD group recovered normal activity and sexual intercourse more rapidly (both p<0.05). The azoospermia rate was lower in the IVD group than in the NSV group at the third and 12th postoperative months. The rate of contraceptive success based on semen analyses was similar in both groups, especially at the 12th postoperative month (94.3% in the IVD group vs. 98.6% in the NSV group; p=0.054). The IVD group had less risk of complications (i.e. pain, congestive epididymitis and sperm granuloma). More subjects reported satisfaction with IVD sterilization than with NSV. The two procedures were similar in terms of surgical complications. The IVD was slightly less effective, but had a lower risk of later adverse events than the NSV technique. The IVD group also reported a higher level of satisfaction. It is now accepted that both medical and surgical practice should be based on reliable and sound clinical evidence. However, randomized control trials comparing surgical interventions have been associated with many problems. The aim of this review is to assess if there has been progress made in establishing the evidence base for surgical interventions in gynaecology.
                Relevant reviews were identified from Cochrane Database of Systematic Reviews (Issue , 2006) and data from individual randomized control trials extracted. Chi-squared test was used to compare quality pre- and post-Consolidated Standards of Reporting Trials (CONSORT) statement. Meta-regression analyses were performed to test the hypothesis that effect size decreased over time. Further multiple linear regression analyses were used to test the hypothesis that precision increased over time and finally a logistic regression model was used to estimate whether treatment effects differed between trials with and without allocation concealment.
                Twenty-three relevant reviews were identified, including 94 trials. The proportion of studies reporting allocation concealment significantly increased after the introduction of the CONSORT statement (P = 0.002). There was a trend towards improvement in precision over time. Similarly, there was a reduction in size of treatment effect over time (log of the ratio of odds ratios per year 0.96; 95% confidence interval 0.93-0.99, P = 0.04).
                Gynaecologic surgical practice appears to be benefiting from improvement in its research base in a subject where practitioners do not participate readily in randomized evaluation. Retinoids enhance differentiation of most epithelial tissues. Epidemiologic studies have shown an inverse relationship between dietary intake or serum levels of vitamin A and the development of cervical dysplasia and/or cervical cancer. Pilot and phase I investigations demonstrated the feasibility of the local delivery of all-trans-retinoic acid (RA) to the cervix using a collagen sponge insert and cervical cap. A phase II trial produced a clinical complete response rate of 50%.
                This randomized phase III trial was designed to determine whether topically applied RA reversed moderate cervical intraepithelial neoplasia (CIN) II or severe CIN.
                Analyses were based on 301 women with CIN (moderate dysplasia, 151 women; severe dysplasia, 150 women), evaluated by serial colposcopy, Papanicolaou cytology, and cervical biopsy. Cervical caps with sponges containing either 1.0 mL of 0.372% beta-trans-RA or a placebo were inserted daily for 4 days when women entered the trial, and for 2 days at months 3 and 6. Patients receiving treatment and those receiving placebo were similar with respect to age, ethnicity, birth-control methods, histologic features of the endocervical biopsy specimen and koilocytotic atypia, and percentage of involvement of the cervix at study. Treatment effects were compared using Fisher's exact test and logistic regression methods. Side effects were recorded, and differences were compared using Fisher's exact test.
                RA increased the complete histologic regression rate of CIN II from 27% in the placebo group to 43% in the retinoic acid treatment group (P = .041). No treatment difference between the two arms was evident in the severe dysplasia group. More vaginal and vulvar side effects were seen in the patients receiving RA, but these effects were mild and reversible.
                A short course of locally applied RA can reverse CIN II, but not more advanced dysplasia, with acceptable local side effects.
                A derivative of vitamin A can reverse or suppress an epithelial preneoplasia, lending further support to the notion that chemoprevention of human cancer is feasible. The purpose of our study was to compare loop diathermy excision and laser excisional conization with respect to treatment time, reliability, effectiveness, and safety.
                Three hundred women with cervical intraepithelial neoplasia attending our colposcopy clinic were randomized to treatment with either loop diathermy excision (group 1, n = 150) or carbon dioxide laser excisional conization (group 2, n = 150), both performed with local anesthesia on an outpatient basis. Student's t or Mann-Whitney test were used to compare continuous data; the chi 2 test was used for categoric data.
                The mean age, parity, histologic features, depth of excision, and occurrence of residual or recurrent disease were similar; however, the mean time required to complete treatment and hemostasis (2.5 +/- 3.6 vs 24.2 +/- 11.8 min), patient discomfort, blood loss (2.77 +/- 3.76 vs 27.15 +/- 17.51 ml; p < 0.001), and considerable thermal artifact affecting histologic interpretation of excision margins (5 cases vs 25 cases; p < 0.01) were significantly less in group 1 than in group 2.
                In our experience outpatient loop diathermy excision is an equally effective, quicker, safer, and more reliable excisional technique than laser excisional conization. The aim of this study was to determine the potential therapeutic benefits of indole-3-carbinol (I3C) in the management of vulvar intraepithelial neoplasia (VIN). Women with histologically confirmed high-grade VIN were randomized to receive 200 and 400 mg/day of I3C. Symptomatology by visual analog scale and vulvoscopic appearance were assessed at recruitment, 6 weeks, 3 months, and 6 months. Tissue biopsy to determine histologic response was obtained at completion of the study period. Urine samples were obtained at each visit to determine 2-hydroxyestrone to 16-alpha-hydroxyestrone ratios. Data from 12 women were suitable for analysis. There was a significant improvement in symptomatology with the introduction of I3C (itch, P= 0.018; pain, P= 0.028). Lesion size and severity were also significantly reduced (size, P= 0.005; appearance, P= 0.046). In addition, there was a significant increase in 2-hydroxyestrone to 16-alpha-hydroxyestrone ratio following commencement of I3C, P= 0.05. However, tissue biopsy from the worst-affected vulval areas revealed no improvement in grade of VIN during the 6-month period, P= 0.317. There were no significant differences in results between those women taking 200 mg/day of I3C and those on 400 mg/day. This study has shown significant clinical improvement in symptomatology and vulvoscopic appearance of VIN with I3C therapy. Further clinical and scientific investigations are required to support these preliminary findings. To compare the effectiveness of two transperitoneal laparoscopic Burch procedures.
                The sample size required was 30 subjects per group to detect a statistically significant estimated difference of 15% between two surgical procedures with an alpha = 0.05 and a power of 0.7. Sixty women affected by genuine stress incontinence (GSI) were enrolled and randomly assigned to two groups of 30 women each. All women were treated with the transperitoneal laparoscopic Burch procedure using nonabsorbable sutures (group A) or Prolene mesh (Ethicon, Somerville, NJ) fixed with tacks or staples (group B). The failure rate was defined subjectively and objectively. The subjective evaluation was performed by asking the women to rate their urine loss on a visual analog scale. The objective evaluation was a clinical evaluation using multichannel urodynamic studies.
                The subjective failure rate was not significantly different between the two groups at 3 months (0% for both groups), 6 months (3.7% versus 3.8% for groups A and B, respectively), and 12 months (7.4% versus 15.4% for groups A and B, respectively) after surgery. At 3 months (3.7% versus 3.8% for groups A and B, respectively) and 6 months (7.4% versus 15.4% for groups A and B, respectively) follow-up, the objective failure rate was not significantly different between the two groups. However, at 12 months after the surgical procedure, the objective failure rate was significantly lower in group A than in group B (11.1% versus 26.9%, respectively; P <.05).
                Transperitoneal laparoscopic Burch colposuspension performed using sutures was more effective than the mesh technique.
The included trial lacked statistical power due to the small number of women in each group and the low number of observed events. Therefore in the absence of reliable evidence regarding the effectiveness and safety of the two surgical techniques for the management of vulval intraepithelial neoplasia precludes any definitive guidance or recommendations for clinical practice.