GnRH antagonist in the adjuvant treatment of a recurrent ovarian granulosa cell tumor: a case report.

BACKGROUND: Ovarian granulosa cell tumors (GCT) are usually treated by surgery and chemotherapy. Successful response to GnRH agonists as an adjuvant therapy has previously been reported. In this case of recurrent GCT, we used a GnRH antagonist. CASE: A 78-year-old woman underwent surgery for an ovarian granulosa cell tumor (pT1a N0 Mx). Six months later, laparotomy revealed an inoperable recurrence of the tumor. Experimental treatment with a GnRH antagonist was not clearly successful. This is in contrast to the previously proven benefit of GnRH agonist therapy in this type of malignancy and to the positive response elicited by GnRH antagonists in epithelial ovarian tumors. CONCLUSION: GnRH antagonist therapy had no demonstrable efficacy in the treatment of a poorly differentiated and aggressive recurrent granulosa cell tumor.

A persistently recurring peri-urethral soft tissue lesion of the vulva.

Various mesenchymal lesions, some of which have only recently been characterized, may affect the vulva. Because of their apparently shared origin from vulvovaginal mesenchyme, these lesions can resemble one another superficially and can be challenging diagnostically. Clinically, benign lesions and tumor-like conditions may mimic a malignant process because of hypercellularity, mitotic activity, and rapid growth. We report on a 84-year-old diabetic and hypertensive woman who had previously undergone skinning vulvectomy for lichen planus and an embolectomy of the left femoral artery. The patient presented with a rapidly growing vulvar mass. The biopsy showed spindle cell proliferation in a loose myxoid stroma with granulation tissue and a mixed inflammatory infiltrate. Based on histology and immunohistochemistry, the initial diagnosis was that of a benign lesion. In view of the persistent recurrence of the lesion and the absence of metastatic spread, we conclude that the lesion has a low-grade malignant potential and suggest the diagnosis of florid cellular reactive pseudosarcomatous myofibroblastic proliferation.

Hormones and menopause: pro.

Since the publication of the first controlled randomised trials with disease event outcomes, it has become fashionable to denigrate hormone replacement therapy (HRT). The lack of protection against cardiovascular disease and the moderate increase of the risk of developing breast cancer and other ailments were given wide publicity by the lay press, which caused a considerable anxiety among users. The fact that a similar or even greater increase in the risk of developing a breast carcinoma is associated with a menarche before the age of 11 years, nulliparity, a first pregnancy after the age of 35 years, obesity, and moderate alcohol consumption was not mentioned. As a consequence, the adverse effects were put out of perspective and public opinion--including the medical profession--was blatantly misled. The reporting by medical journals was frequently equally biased. In the light of available evidence one can objectively state that HRT tailored to the needs of the individual woman and started around or shortly after the menopause improves her quality of life at the cost of a negligible risk. Oestrogens are ideally administered parenterally. In women who did not undergo a previous hysterectomy, the progestin should be delivered in the uterine cavity rather than systemically, which might lead to a lesser risk of breast malignancy. Indeed, this latter is not or not significantly increased when unopposed oestrogens are administered. Likewise, the risks of cardiovascular disease and stroke are not increased in treated women, aged 50-59 years. In older women, HRT initiated in the perimenopause can be continued using lower doses.

Low-grade endometrial stromal sarcoma treated with the aromatase inhibitor letrozole.

BACKGROUND: Low-grade endometrial stromal sarcoma is an indolent steroid responsive tumor. Successful hormonal treatment, most commonly with megestrol acetate, has been reported. CASE: A 76-year-old woman underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy 25 years earlier allegedly for a benign condition. She presented to us with postrenal kidney failure and a huge pelvic mass compressing both ureters. After transvaginal trough-cut biopsy of the mass, the diagnosis of low-grade endometrial stromal sarcoma with a high expression of alpha-estrogen receptor was made. The patient was treated with letrozole only with a spectacular response. CONCLUSION: To the best of our knowledge, this is the first case for which letrozole was used on long-term basis as first-line hormonal treatment for a recurrent low-grade stromal sarcoma.

A 10-year follow-up after Kegel pelvic floor muscle exercises for genuine stress incontinence.

OBJECTIVE: To determine the outcome 10 years after an individual course of pelvic floor muscle (PFM) exercises for genuine stress incontinence. PATIENTS AND METHODS: Postal questionnaires were sent to 52 women who had undergone PFM training 10 years earlier, and their medical files were reviewed. The main outcome measures were the patients' self-assessment of therapy outcome, the frequency of PFM exercises at home, and the demand for surgery after physiotherapy. RESULTS: Forty-five women (87%; mean age 61 years) were suitable for analysis. On completing the course of PFM exercises, physiotherapy had been apparently successful in 24 (53%), and considered to have failed in 21 women (47%). Sixteen of the 24 successful patients remained satisfied with their urinary continence when reassessed 10 years later; two women had undergone surgery (8%). In the group where physiotherapy initially failed, five women (24%) who had not had surgery claimed to be much improved; 13 women (62%) had undergone surgery. Overall, women in whom the conservative treatment of stress incontinence had produced an improvement over the 10 years had practised PFM exercises more regularly (76%) than the others (55%; not significant). However, an active voluntary PFM contraction before a sudden intra-abdominal pressure rise ('perineal lock') appeared to be responsible for most of the success. CONCLUSIONS: When PFM training is initially successful, there is a 66% chance that the favourable results will persist for at least 10 years.

Vaginal hysterectomy.

The authors report on their experience of vaginal hysterectomy in a prospective series of 14 patients with myomatous uteri of the size of 14 to 20 weeks' gestation. The mean uterine volume at the time of surgery was that of 16 1/2 weeks' gestation. The largest myoma had a diameter of 11.6 cm. Five of the patients were also scheduled to undergo bilateral oophorectomy. The paracervical tissues were infiltrated with a dilute solution of lignocaine and adrenaline. Circumferential incision and reflection of the vaginal wall, dissection of the bladder cephalad, opening of the vesico-uterine fold anteriorly and the pouch of Douglas posteriorly were performed initially. This was followed by clamping, division and ligation of the sacro-uterine and cardinal ligaments and of the uterine vessels, as is done during a vaginal hysterectomy. The next step depended on the size and other features of the uterine corpus and included bisection, myomectomy, morcellation and coring. BISECTION: The cervix was grasped on both sides and the uterus was bisected sagittally towards the fundus, using a knife. The bisection, carried out first along the posterior uterine wall, was aided by the repeated repositioning of the vulsella close to the apex of the incision, combined with rotation of the cervical portion of the uterus around the public arch. If necessary, the uterus was rotated back to its original position and the bisection pursued anteriorly. Complete bisection often allowed half the uterus to be delivered through the vagina and the ovarian pedicle to be secured; the same was then done with the other half of the uterus. Myomectomy was frequently combined with bisection or morcellation. Smaller myomas were removed in one piece while larger ones were morcellated and removed in fragments, one of the vulsella always being attached to the residual bulk of the myoma. Morcellation was carried out on the uterus when despite bisection or myomectomy no further descent was possible. Bisection was recommenced as soon as further descent of the uterus could be achieved after myomectomy and morcellation. Coring was performed instead of bisection when dealing with smaller uteri without any distinct large myoma. A circumferential incision was made at the level of the uterine isthmus about 5 mm into the substance of the corpus. A central core of tissue around the uterine cavity was then excised by progressively undercutting the serosal surface of the uterus towards the fundus. Once the uterus was delivered into the vagina, the hysterectomy was completed in the usual fashion. All 14 procedures with or without oophorectomy or salpingo-oophorectomy were completed successfully. The mean weight of the uteri was 639 g (range 380-1100 g), the mean operating time was 84 minutes (range 30-150 minutes) and the mean operative blood loss was estimated at 296 ml (range 100-800 ml). One patient was given a blood transfusion immediately postoperatively. Six women had macroscopic haematuria that cleared up within 24 hours. There were no other important complications. Postoperative hospital stay averaged 3.7 days (range 2-9 days). Only 2 patients remained in hospital for more than 4 days after surgery. All women had recovered fully by the time of their follow up appointment.

A multicenter European survey of the attitudes to contraception in women at high risk or with established cardiovascular disease.

OBJECTIVES: The survey was designed to study the attitudes of gynecologists from 11 European centers providing guidance in contraception to women at high risk and women with cardiovascular disease. METHODS: Attitudes were registered by means of a standard questionnaire. RESULTS: Most contributors reported that, in women with venous thrombosis (10/11), deep venous thrombosis (10/11), coagulation disorders (11/11) and stroke (8/11), they prefer to prescribe methods other than combined oral contraceptives (COCs). A history of myocardial infarction was considered a relative contraindication and some experts suggested that, in some cases, the use of third-generation COCs may be possible. COCs were not recommended in women with severe cardiovascular disease and in those over 35 years of age with light or moderate cardiovascular disease, heavy smokers (over 20 cigarettes per day), or those presenting with severe hyperlipidemia. CONCLUSION: The pill is not considered appropriate for women with clinically established cardiovascular diseases or in cases where more than two coronary risk factors exist. COCs may safely be given to women with elevated blood pressure as long as it is lower than 160/100 mmHg, in cases of light and moderate cardiovascular disease as long as the patient is less than 35 years of age, in women who are not heavy smokers, in the presence of a light or moderate degree of hyperlipidemia, and in uncomplicated diabetes mellitus provided that there are no additional risk factors. In these cases, third-generation COCs are preferred. The co-operation of the cardiologist is desirable in order to classify cardiovascular disease and for patient follow-up.

Singleton pregnancy after in vitro fertilization: expectations and outcome.

OBJECTIVE: To determine if singleton in vitro fertilization (IVF) pregnancies carry a higher risk for ante- and perinatal complications compared with naturally conceived pregnancies. METHODS: One hundred forty singleton pregnancies conceived by IVF and 140 matched control pregnancies conceived naturally were analyzed with respect to the incidence of antepartum complications and perinatal outcome. The study was conducted in a university hospital, and pregnancy and labor were managed according to a standardized protocol. RESULTS: Sixteen IVF pregnancies and two control pregnancies ended preterm (P < .01), resulting in the birth of infants with lower birth weight in the former group (P = .01). Except for placenta previa, which occurred four times in IVF pregnancies and not in the control group, no differences in antenatal events were found. Labor was more often induced in IVF pregnancies than in control pregnancies. Elective cesarean delivery for obstetric reasons was performed ten times in the IVF group and never in the controls (P < .01). However, once in labor, no differences in the rate of instrumental or cesarean delivery were found. There were eight minor congenital malformations in the IVF group and none in the control group (P < .01). CONCLUSION: Even when managed in a single center, IVF pregnancies carry a greater antenatal risk than matched controls. Once in labor, and managed in a similar fashion, the outcome does not differ from that of controls.

Normal pregnancy in primary alveolar hypoventilation treated with nocturnal nasal intermittent positive pressure ventilation.

Nocturnal nasal intermittent positive pressure ventilation (NIPPV) is increasingly used to treat chronic respiratory failure in a wide variety of conditions (myopathies, Ondine's curse, kyphoscoliosis, etc.) and allows a normal everyday life. Some of these diseases affect women of childbearing age. We report on a young woman suffering from primary alveolar hypoventilation, who presented with limitation of daytime activities, severe oxygen desaturation during sleep, polycythaemia and pulmonary hypertension. These abnormalities completely reversed after a few months of NIPPV applied through a nasal mask. Whilst under ventilatory assistance during sleep, she had an uneventful pregnancy and delivery of a normal baby. We suggest that in selected patients requiring NIPPV, pregnancy can be contemplated with a reasonable level of safety both for the mother and the child, provided that adequate mechanical ventilatory assistance during sleep is maintained throughout pregnancy.

Study of numerical aberrations of chromosome 1 by fluorescent in situ hybridization and DNA content by densitometric analysis on (pre)-malignant cervical lesions.

In an attempt to determine whether the fluorescent in situ hybridization (FISH) can be used as a rapid approach for the identification of aneuploidy in premalignant cervical smears, a centromeric probe for chromosome 1 was used. The results from the FISH experiments were compared with measurements of the overall DNA content obtained by means of an image analysis system. With progression to neoplasia, a decrease of the frequency of cells with two spots was observed, due to an increasing polysomy of chromosome 1. As far as the DNA content was concerned, an increasing DNA index and 5C-exceeding ratio (fraction of cells with a DNA content higher than 5C) was observed. Classification of the FISH results by a linear discriminant analysis revealed that 67.6% of the cases were classified in agreement with the CIN classification. These data suggest that chromosome 1 may be considered as a marker chromosome for pre-malignant cervical lesions and that the DNA content measurements are complementary to the FISH results.

Detection of premalignant stages in cervical smears with a biotinylated probe for chromosome 1.

Fluorescence in situ hybridization with (peri-)centromeric probes is an easy method to detect numerical aberrations in nonmitotic and mitotic cells. In this study, cervical smears of premalignant and malignant stages (26 controls, 15 CIN I, 12 CIN II, and 15 CIN III cervical smears) were analyzed for the presence of numerical aberrations of chromosome 1 with a centromeric DNA probe (1q12). With more severe stages a decrease of disomy was observed, merely due to a gain of extra copies of chromosome 1; in some cases, however, monosomy was detected. The frequencies of disomy for chromosome 1 ranged from 65.3% to 95.0% in the controls, from 71.3% to 94.3% in CIN I, from 59.2% to 91.5% in CIN II, and from 23% to 96.2% in CIN III. Polysomy ranged from 0% to 5.7% in the controls, from 0% to 14.4% in CIN I, from 0.9% to 30.8% in CIN II, and from 0.8% to 69.6% in CIN III. Monosomy ranged from 2.6% to 34.1% in the controls, from 0% to 17.5% in CIN I, from 3.6% to 27.5% in CIN II, and from 0.9% to 31.4% in CIN III. The results show that screening for aneuploidy of chromosome 1 allows a good discrimination between control samples and dysplasia. These data suggest that chromosome 1 may be a marker chromosome. They are in accordance with previous cytodensitometric analyses, where already in the preneoplastic stages an increased DNA content (polyploidization with subsequent aneuploidization) is observed.

Disseminated peritoneal leiomyomatosis. An unusual case.

Disseminated peritoneal leiomyomatosis (DPL) is a very rare disorder, characterized by the presence of multiple intraabdominal smooth muscle nodules and frequently associated with a high estrogen production. We report on a 43-year-old woman with DPL and simultaneous bilateral ovarian cystic teratomas. There were no overt endocrine abnormalities. Due to distinct cellular pleomorphism on a frozen section, complete removal of smooth muscle nodules was suggested, but could not be achieved because of severe bleeding. Two years after resection of the ovarian tumors but with residual DPL, the patient is doing well, with no evidence of malignant disease.