Doron Zarfati

Involvement of heparanase in the pathogenesis of localized vulvodynia.

Summary Recently, we have shown that vestibular hyperinnervation and the presence of 8 or more mast cells in a 10 × 10 microscopic field can be used as diagnostic criteria in localized vulvodynia (vulvar vestibulitis). We have also documented that degranulation of mast cells occurs in these cases. The present study further examines the characteristics of vestibular hyperinnervation and mast cell function in localized vulvodynia to elucidate if the 2 processes-hyperinnervation and mast cell increase and degranulation-are related. We examined vestibular tissue from 7 women aged 18 to 48 with severe localized vulvodynia and from 7 healthy control women. Parallel sections were stained by Giemsa and then immunostained for CD117 and heparanase. Nerve fibers that expressed protein gene product 9.5 were examined. Tissues from women with localized vulvodynia documented a significant increase in vestibular mast cells, subepithelial heparanase activity, and intraepithelial hyperinnervation compared with healthy women. This is the first documentation of heparanase activity in localized vulvodynia. Heparanase, which is degranulated from mast cells, is capable of degrading the vestibular stroma and epithelial basement membrane, thus permitting stromal proliferation and intraepithelial extension of nerve fibers, as seen in the present study. The hyperinnervation has been thought to cause the vestibular hyperesthesia distinctive of localized vulvodynia.

Predicting the outcome of surgical treatment of vulvar vestibulitis

Objective To identify predictive factors for success or failure of perineoplasty for severe vulvar vestibulitis. Methods Seventy-nine women with severe vulvar vestibulitis underwent perineoplasty by a single surgeon during 1992–1994. Sixty (76%) who experienced a complete response were compared with 19 (24%) who had an incomplete response. Using univariate and then multivariate (logistic regression) analysis, the two groups were compared with regard to preoperative demographic, social, and medical variables, as well as physical findings in the vestibule. Results The complete- and incomplete-response groups were similar in all comparisons except for constant vulvar pain of vestibular origin (in addition to dyspareunia) and the presence of symptoms since first coitus. On multiple logistic regression, these characteristics had odds ratios (and 95% confidence intervals) of 4.97 (1.49, 16.63) and 5.83 (1.74, 19.55), respectively. Conclusion An incomplete response to perineoplasty may be anticipated in women with vulvar vestibulitis associated with dyspareunia since their first episode of inter-course and in those with associated persistent vulvar pain. Treatment approaches other than surgery should be considered for such patients.

Perineoplasty compared with vestibuloplasty for severe vulvar vestibulitis

Objective To evaluate the efficacy of vestibuloplasty (vestibular undercutting without excision) to treat severe vulvar vestibulitis.

A randomized comparison of prostaglandin E2 oxytocin, and the double-balloon device in inducing labor

Objective To compare the efficacy of three methods for ripening and dilating the unfavorable cervix for induction of labor. Methods Pregnant women having an indication for induction of labor with a singleton vertex fetus, intact membranes, and Bishop score of no more than 4 were randomized to one of three induction methods: intravaginal prostaglandin (PG) E2, tablets (3 mg) followed by a second dose if labor did not start; continuous intravenous oxytocin drip; or the Atad Ripener Device, with inflation of both balloons and removal after 12 hours. For all patients, the cervix was assessed by the same investigator before induction and 12 hours later. Results Thirty subjects were included in the PGE2 group, 30 in the oxytocin group, and 35 in the Atad Ripener Device group. The postpartum course was comparable in all. The change in Bishop score in the PGE2 and Atad Ripener Device groups was significantly better than in the oxytocin group (median and range of 5 [0–9] and 5 [0–7], respectively, versus 2.5 [0–9]; P ≤ .01). Cervical dilation more than 3 cm was more frequent in the Atad Ripener Device group compared with both the PGE2 and oxytocin groups (85.7 versus 50 and 23.3%, respectively; P ≤ .01). The trial of induction failed in only two patients (5.7%) in the Atad Ripener Device group, compared with six (20%) in the PGE2 and 16 (53.3%) in the oxytocin groups (P ≤ .001). Mean (± standard deviation) induction-to-delivery interval was 21.3 ± 7.0 hours in the Atad Ripener Device group, 23.2 ± 12.5 hours in the PGE2 group, and 28.2 ± 14.7 hours in the oxytocin group. The success rate for vaginal delivery was significantly better in the Atad Ripener Device and PGE2 groups compared with the oxytocin group (77.1 and 70%, respectively, versus 26.7%; P ≤ .01). Conclusion The Atad Ripener Device had a significantly better success rate for cervical dilation and a lower failure rate than those for PGE2 and oxytocin. The PGE2 and Atad Ripener Device groups had better results than the oxytocin group in regard to Bishop score change and induction-to-delivery interval. The Atad Ripener Device may be a superior method for cervical ripening and labor induction in patients with unfavorable cervices.

Vulvar vestibulitis: physical or psychosexual problem?

OBJECTIVE To examine whether vestibulitis has a physical or a psychosexual etiology. DATA SOURCES MEDLINE was searched to retrieve publications dating from January 1981 through June 1998 that evaluated the outcomes of surgical treatment and the psychosexual theory of the origin of vestibulitis. INTEGRATION: Articles were analyzed for methods of subject selection and surgery, surgical outcome, and length of follow-up. RESULTS A significant decrease in symptoms (complete responses + partial responses) was reported by 89% of 646 women who had perineoplasty for vulvar vestibulitis. Complete resolution of dyspareunia with surgical treatment was reported in 72% of 512 women whose cases were reviewed in studies in which complete responses and partial responses were evaluated separately. Women with vestibulitis did not differ from the normal population with respect to marital satisfaction, psychologic distress, or psychopathology. A suggestion that childhood sexual abuse caused vestibulitis has not been confirmed. The findings of somatization and shyness might be explained as results rather than causes of vulvar vestibulitis. CONCLUSION We do not agree that vestibulitis is a psychosexual problem and one that should not be treated surgically. A high rate of success can be achieved with proper surgical treatment.

Enoxaparin treatment for vulvodynia: a randomized controlled trial.

OBJECTIVE: To estimate the effectiveness of enoxaparin—a low-molecular-weight heparin with antiheparanase properties—in treating localized provoked vulvodynia. METHODS: Forty women with severe localized provoked vulvodynia were randomly and blindly assigned to self-administer either 40 mg enoxaparin or saline subcutaneously for 90 days. Dyspareunia and local sensitivity were evaluated before, at the end, and 90 days after treatment. The most painful focus was biopsied at the beginning of the study and a parallel site at the end of study for mast cells, PGP 9.5 nerve fiber staining, and heparanase quantification. RESULTS: The enoxaparin-treated women showed a greater reduction in vestibular sensitivity at the end of treatment and 3 months later (29.6% compared with 11.2%, P=.004). Seventy-five percent (15 of 20) of them reported more than 20% pain reduction compared with 27.8% (five of 18) in the placebo group (P=.004). Seven enoxaparin-treated women compared with three in the placebo group had almost painless intercourse at the end of the study. In women who had improvement of sensitivity at the site parallel to the original biopsy site, there was a histologically documented reduction in the number of intraepithelial-free nerve fibers in the enoxaparin group. CONCLUSION: Enoxaparin reduced the vestibular sensitivity and dyspareunia, concomitant with a reduction in intraepithelial free nerve fibers, in women with localized provoked vulvodynia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00874484. LEVEL OF EVIDENCE: I

Persistent vulvar vestibulitis: the continuing challenge.

A continuing challenge in the management of women with vulvar vestibulitis is the patient who has not responded to surgical treatment. The main reason for persistent dyspareunia is failure to excise the sensitive periurethral tissue in the primary operation. In other cases, the Bartholins glands may be the source of the pain. A low oxalate diet, the administration of interferon, and biofeedback training of the lower pelvic muscles-treatments that are used as a first-choice approach for vulvar vestibulitis, may all work in the postoperative patient. The management of a patient with residual vestibulitis should be conservative, and only when medical measures fail, do we consider additional surgical methods such as Bartholins gland resection or repeat perineoplasty.

Decision-making in the colposcopy clinic – a critical analysis

OBJECTIVE To consider the omission of several diagnostic steps from the management of patients with high-grade squamous intraepithelial lesion (SIL) by analyzing the role of each step on the choice of treatment. STUDY DESIGN Each diagnostic procedure was correlated to the treatment and outcome in 87 women with high-grade SIL. Treatments considered were large loop excision of the transformation zone (LLETZ) cold knife conization, and CO2 laser vaporization. RESULTS Unsatisfactory colposcopy (P< or =0.01) and positive endocervical curettage (ECC) specimen (P< or =0.01) were essential for choice of treatment. CIN2 diagnoses of the preoperative cervical biopsy were rediagnosed as CIN3 based on the surgical specimen in 57% of the cases. The margins of 33 and 23% of surgical specimens removed by LLETZ or knife conization, respectively, displayed CIN involvement. Forty and 47% of these patients, respectively, later developed recurrent CIN. CONCLUSIONS Omission of colposcopy and ECC could have resulted in sub-optimal treatment in many cases. Excision by LLETZ or knife conization is recommended for cases of CIN2 and CIN3. Follow up is imperative for patients with involvement of the margins.

Tools for post LEEP surveillance.

Recurrences of cervical intraepithelial neoplasia (CIN) as well as invasive cervical carcinoma have been reported to arise following ablative or excisional treatment for cervical intraepithelial neoplasia. This review utilizes MEDLINE and National Library of Medicine’s PubMed review of the various screening tools used in follow-up protocols for women treated by loop excision for CIN. Cervical cytology, colposcopy, endocervical curettage and HPV typing have been advocated for use as tools for follow up. Involvement of the surgical margins and the presence of HPV-DNA are associated with higher risks of recurrence and should be taken into consideration. The psychological impact of undergoing colposcopy may affect compliance with follow-up visits and should be dealt with appropriately. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to list the various tools that can be used for the surveillance of patients after treatment for CIN, to compare the advantages and disadvantages of each surveillance method, and summarize methods to improve compliance with follow-up.

Re: Causation of vulvar vestibulitis

It is often said that there is nothing new in clinical medicine. This certainly appears to be the case with this report of a ‘new surgical technique’. I recognised the description of the technique and found it in my undergraduate obstetric textbook, A Textbook of Obstetrics by Mayes. With this in mind, I obtained a copy of Huntington’s original article published in the Boston Medical and Surgical Journal on 14 April 1921. In it he states ‘Peritoneal cavity opened, and what proved to be the lower uterine segment with appendages drawn into the crater presented at the wound. A thick bite of the uterus was seized with Ellis forceps in the median line just inside the crater. With moderate traction it was brought above the ring, and a bite seized lower down, and so bit by bit the uterus was drawn back through the ring. It appeared firm, but rather pale, but the colour returned rapidly, and no attempt was made to fix the uterus’. At no time did Huntington refer to correcting the inversion by pulling on the round ligaments. Mayes in his textbook refers to an article on acute inversion of the uterus treated by Huntington’s operation by Bigby, Greeves and Kinch. There they describe ‘the technique consists of an abdominal incision about 3 inches long to expose the inversion cup. The operator and his assistant, using Allis’s forceps, grasp the posterior uterine wall on either side, about 3/4 inch below and inside the inversion cup and draw it up. A further two pairs of Allis’s forceps then grasp the uterus at a lower level and elevate it; the first pair is then removed and reapplied below the second pair and so on until the fundus is up and reinversion is complete’. They state that the procedure takes 15 min to perform. Whilst it is certainly not a ‘new procedure’ it is one that our colleagues would do well to remember if they run into a similar situation. Yours sincerely,