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Objective: To investigate the efficacy of topical treatment with imiquimod 5% cream, an immune response modifier, in patients with vulvar intraepithelial neoplasia (VIN) 2/3., Study Design: Fifteen women (aged 35-51) with histologically proven multifocal VIN 2/3 without invasion, were entered into a prospective, observational, pilot study. Imiquimod 5% cream was applied by the patient to the vulvar lesions one to three times a week at night. Clinical response was analyzed by macroscopic examination and categorized as complete (CR) or partial (PR)., Results: Four patients achieved CR (27%) and nine patients, PR (60%) after 6-34 weeks of treatment. Two patients discontinued medication. CR was reached after 6, 7, 11 and 30 weeks of treatment., Conclusion: This pilot study showed the potential beneficial effect of imiquimod 5% cream in multifocal VIN 2/3. In contrast to current surgical treatment, imiquimod focuses on the cause of VIN and preserves the anatomy and function of the vulva. Therefore, imiquimod may prove to be the treatment of choice in multifocal, high grade VIN.

van Beurden M, van der Vange N, ten Kate FJW, de Craen AJM, Schilthuis MS, Lammes FB. Restricted surgical management of vulvar intraepithelial neoplasia 3: Focus on exclusion of invasion and on relief of symptoms. Int J Gynecol Cancer 1998; 8: 73-77. A study was undertaken to determine the effectiveness of extensive and restricted surgery for vulvar intraepithelial neoplasia (VIN) 3. All consecutive patients with VIN 3 admitted to a tertiary referral hospital were included. The main outcome measures were relief and recurrence of symptoms and progression to invasive disease in patients with VIN 3 after extensive or restricted surgery. Of every vulvoscopic visible lesion a biopsy was taken to establish extent and grade of VIN and to rule out invasive carcinoma. Patients with unifocal VIN 3 underwent extensive surgery. Patients with multifocal VIN 3 underwent extensive or restricted surgery or an expectant management was adopted, depending on the existence of symptoms and the presence of invasive vulvar carcinoma. Forty-seven patients were evaluated. Eighty-three percent of patients had a long history of symptoms. Eight patients (17%) had unifocal VIN 3. In 9% of the patients a superficially invasive vulvar carcinoma was found, ie with a depth of invasion of 1 mm or less. Only 20% of the extensively operated patients had free surgical margins. There was recurrence of symptoms in all of the extensively operated patients, in contrast to a 26% persistence or recurrence rate of symptoms in the restrictedly operated patients. In patients with multifocal VIN 3 who underwent restricted surgery, young age of the patient (P = 0.02) and large extension of VIN 3 (P = 0.02) were significant factors in predicting persistence or recurrence of symptoms. Only once was a superficially invasive vulvar carcinoma diagnosed during follow-up, and this was in an extensively operated patient. Vulvoscopically directed biopsies in VIN 3 are a safe method to exclude invasive disease. Restricted surgery is effective in relieving symptoms in multifocal VIN 3.

Human papillomavirus (HPV) DNA in vulvar intraepithelial neoplasia (VIN) is associated with multifocality of VIN III and with multicentricity of other neoplastic squamous lesions in the cervix and vagina. The aim of this study was to establish the prevalence and type of HPV DNA in the lesions of vaginal intraepithelial neoplasia (VaIN) and cervical intraepithelial neoplasia (CIN) in patients with VIN III using the polymerase chain reaction (PCR). HPV DNA detection and histologic analysis were performed on alternating sections of paraffin-embedded biopsies of concomitant CIN and VaIN in 27 patients with VIN III. PCR was performed with consensus primers and HPV typing was performed by direct sequencing of the PCR amplimers. HPV DNA was detected in all VIN III lesions (93% contained HPV-16 DNA); in 96% of the CIN lesions (73% contained HPV-16 DNA); and in all VaIN lesions (75% contained HPV-16 DNA). The HPV type was not the same in 22% of the different lesions of VIN, CIN, and VaIN, even if the biopsies were taken at the same time.

Objective: To determine the normal vulvar findings by naked eye examination and by vulvoscopy in healthy women without vulvar complaints., Design: Observational study., Population: Forty healthy volunteers without vulvar complaints recruited via a newspaper advertisement., Methods: Vulvar examination, human papillomavirus (HPV) polymerase chain reaction of vulvar and cervical swabs, saline and KOH smears and vulvoscopy before and after the application of 5% acetic acid., Main Outcome Measures: Prevalence of vestibular erythema, vestibular papillomatosis, HPV infection on the vulva and in the cervix and vulvoscopic findings., Results: The mean age of the women was 37.8 years (median 38.0, range 21-56). Nine women were current smokers and 21 had previously smoked. Naked eye vulvar examination showed vestibular papillomatosis in 13 women (33%) and vestibular erythema in 17 women (43%). The touch test was positive in 9 of the 17 women (53%) with vestibular erythema. Vulvoscopy after the application of acetic acid 5% showed an acetowhite vestibule in all women. Twelve women (30%) had acetowhite lesions outside the vestibule. Six women (15%) were positive for HPV DNA. The presence of HPV DNA did not correlate with vestibular erythema or vestibular papillomatosis. There was a weak association between HPV DNA and acetowhite lesions outside the vestibule (P = 0.055, Fisher's exact test). In this group the younger women significantly more often had vestibular papillomatosis (t-statistic = 3.07; P = 0.003) and women who smoke more often had a genital HPV infection (P = 0.016, Fisher's exact test)., Conclusions: Vestibular erythema, vestibular papillomatosis, and acetowhite lesions are common in this group of healthy women without vulvar complaints.

Objective: To assess the value of hysterosalpingography (HSG) in diagnosing tubal patency and peritubal adhesions using laparoscopy with chromopertubation as the gold standard., Design: Meta-analysis of 20 studies comparing HSG and laparoscopy for tubal patency and peritubal adhesions., Patients: Four thousand one hundred seventy-nine patients with infertility in 20 studies., Intervention: Hysterosalpingography and diagnostic laparoscopy as part of infertility workup., Main Outcome Measure: Tubal patency and peritubal adhesions., Results: For tubal patency the reported sensitivity and specificity differed between studies. In a subset of studies that evaluated HSG and laparoscopy independently, a point estimate of 0.65 for sensitivity and 0.83 for specificity was calculated. For peritubal adhesions a summary receiver operating characteristic curve could be estimated., Conclusions: Although HSG is of limited use for detecting tubal patency because of its low sensitivity, its high specificity makes it a useful test for ruling in tubal obstruction. For the evaluation of peritubal adhesions HSG is not reliable.

Ovaries are seldom subject to metastases and therefore their preservation is possible in radical cervical cancer surgery. However, with postoperative radiotherapy they cannot be preserved unless they are placed outside the radiation field. The practicality of this transposition was analysed in a series of 126 patients with cervical cancer. The ovaries were transposed intraperitoneally in a lateral and cranial direction in 44 of the 64 women under the age of 50 years. In 16 of these 44 women, only one ovary could be preserved and transposed. A critical analysis was performed of the ovaries' new location by plotting their position, marked by 2 clips each, in a single pelvis. In 68% of the women at least one ovary was placed outside the radiation field. However, because of scattered radiation, i.e. 5% of the total radiation dose at a distance of 4 cm outside the radiation field, a substantial loss of ovarian function may occur. In 32% of the women at least one ovary received less than this 5%. Optimal transposition may be achieved after extension of the abdominal incision. However, this will be unnecessary in most cases, since postoperative radiotherapy will be indicated in only approximately 15% of the women.

There is a structural similarity between phenolphthalein and the triphenylethylenes which are known to interact with the estrogen receptor of human breast tissue. Phenolphthalein (10 microM) competed with estrogen for binding to MCF-7 human breast cancer cells in tissue culture and induced the synthesis of the progesterone receptor. The antiestrogen 4-hydroxytamoxifen blocked progesterone receptor induction both by estradiol and by phenolphthalein. Both estradiol (0.1 nM) and phenolphthalein (10 microM) stimulated cell growth as measured by DNA and protein assays. This growth stimulation was blocked by 4-hydroxytamoxifen. Phenolphthalein glucuronide, the major phenolphthalein metabolite, did not inhibit estrogen binding, induce progesterone receptor synthesis, or stimulate MCF-7 cell growth in culture. Yellow phenolphthalein, an impure phenolphthalein preparation used in nonprescription laxative preparations, had similar properties to pure phenolphthalein. Physicians should be aware of the weak estrogenic action of phenolphthalein, especially when recommending laxatives for breast cancer patients with confirmed liver and mesenteric metastases.