Biphasic sarcomatoid carcinoma or carcinosarcoma of the breast: prognosis and therapy.

Biphasic sarcomatoid carcinoma of the breast represents only 0.2% of all breast cancer. Due to its rarity and repetitive reclassifications little is known about optimal treatment modalities. These tumours form a diagnostic and therapeutic challenge. The present report describes our experience with a case of biphasic sarcomatoid carcinoma of the breast and a review of the relevant literature is discussed.

Detection of estrogen DNA-adducts in human breast tumor tissue and healthy tissue by combined nano LC-nano ES tandem mass spectrometry.

For the first time estrogen DNA-adducts were identified in DNA human breast tumor tissue using nano-LC coupled to nano-Electrospray Tandem Mass Spectrometry. Normal breast tissue was analyzed analogously. The data obtained in the five breast tumor and five adjacent normal tissue samples were compared qualitatively, but no straightforward difference was observed. Prior to LC-MS analysis the DNA was enzymatically hydrolyzed to a nucleoside pool. The DNA-hydrolysates were directly injected onto a column switching system developed for on-line sample clean-up and subsequent analysis of the DNA-adducts. In four patients using Premarin, DNA-adducts of 4-hydroxy-equilenin (4OHEN) were detected. All except three samples contained DNA-adducts from 4-hydroxy-estradiol or 4-hydroxy-estrone. Also DNA isolated from eight alcohol fixed and paraffin embedded breast tumor tissue showed the presence of different estrogen DNA-adducts. Worthwhile mentioning is the presence of adducts responding to m/z 570 > m/z 454 transition. This is a well-known SRM-transition indicative for the presence of the 2'-deoxyguanosine (dGuo) adduct of Benzo[a]pyrene.

Acardiac amorphous twin with prune belly sequence in the co-twin.

We describe a twin with acardia acephalus or "Twin Reversed Arterial Perfusion Sequence" and prune belly sequence in the co-twin. In a former quite similar case a prune belly appearance of the co-twin of an acardiac fetus was found to be secondary to the ascites caused by cardiac failure. In the present case, we are dealing with the prune belly sequence as a separate condition, given the fact there were no signs of ascites or cardiac failure. We also found associated anomalies: agenesis of the left ureter and kidney, dysplastic right kidney and anal atresia. Urinary tract obstruction has never been described in the co-twin of an acardiac amorphous fetus.

Inhibition of natural killer cell activity by retroplacental sera as compared to peripheral sera. Lack of influence of immune complexes.

A decrease of natural killer cell activity (NKCA) during human pregnancy might contribute to the acceptance of the allogeneic fetus by the maternal host. The inhibition of NKCA might be due to serum factors derived from the trophoblast. We focused especially on the role of immune complexes, as it has already been described that these complexes depress NKCA and as they are found frequently in retroplacental serum. We have compared the influence of 19 paired retroplacental and peripheral blood sera on NKCA of normal donors. One peripheral and eight retroplacental sera contained immune complexes. Normal donor mononuclear cells were incubated with carboxyfluorescein-labeled K562 cells in the presence of retroplacental serum or peripheral serum. NKCA was measured on a FACS Analyzer. Ten of 19 retroplacental sera inhibited NKCA significantly in comparison to the corresponding peripheral serum (P = 0.003). There was no correlation between NKCA and the immune complex level. We conclude that, as compared to peripheral serum taken at delivery, there is a retroplacental serum-induced inhibition of NKCA, which is not correlated with the presence of immune complexes.

Immunohistochemical study of topoisomerase II-alpha expression in primary ductal carcinoma of the breast.

AIMS: To study the patterns of expression of topoisomerase II-alpha in primary invasive ductal breast carcinomas; to correlate this expression with clinicopathological data and prognosis. METHODS: Cryostat sections from 63 primary invasive ductal breast carcinomas were stained immunohistochemically for topoisomerase II-alpha. Nuclear immunoreactivity was quantified by counting at least 500 cells in different random fields and results were expressed as per cent of cells staining positively for topoisomerase II-alpha. RESULTS: Topoisomerase II-alpha nuclear immunoreactivity (median 14% of nuclei; range 2-62%) was detected in all tumours with highly variable intertumour and intratumour nuclear reactivity. Higher levels of topoisomerase II-alpha expression were strongly related to higher tumour grade, larger tumour size, nodal status, and the presence of distant metastases at diagnosis. No correlation was found with menopausal status, steroid hormone receptor status, disease free survival, or overall survival. CONCLUSIONS: Expression of topoisomerase II-alpha is related to the presence of poor prognostic factors. Immunohistochemical assessment of topoisomerase II-alpha expression in breast cancer could be potentially useful for tailoring chemotherapy with topoisomerase II inhibitors.

Disseminated intravascular coagulation and the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe preeclampsia.

To clarify the role of disseminated intravascular coagulation (DIC) in women with the hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, serial coagulation studies were performed prospectively in 18 patients. A semiquantitative DIC scoring system was used retrospectively to augment the diagnostic confidence of coagulopathy. At the time of admission to the hospital, three patients showed no evidence of DIC, eight had suspected DIC, and seven had manifest DIC. The intravascular coagulation process was progressive in all patients; upon delivery, eight patients proved to have suspected DIC and ten had manifest DIC. The laboratory criteria of DIC were found to agree with the degree of organ dysfunction. Patients with manifest DIC at delivery developed significantly more life-threatening maternal complications than did patients with suspected DIC (P less than .02). Conservative management was not possible in any patients who were admitted with overt DIC because of deterioration of maternal and fetal status. Application of a sensitive DIC scoring system may be valuable in managing patients with the HELLP syndrome and selecting patients who may be treated expectantly.

Contrast-enhanced MR imaging of breast lesions and effect on treatment.

PURPOSE: To assess the value of local staging with preoperative magnetic resonance imaging (MRI) in patients with suspect breast lesions and the effect on therapeutic approach. MATERIALS AND METHODS: Two hundred and four consecutive women with suspect breast lesions on clinical examination (CE) and/or mammography (MX) and/or ultrasound (US) underwent preoperative contrast-enhanced MRI. Detection of multifocal, multicentric and bilateral breast cancer by all three imaging modalities was evaluated. Results of preoperative breast MRI were discussed with the treating surgeons. The type of therapeutic change after preoperative MRI was marked on a questionnaire (none, additional fine needle aspiration, core biopsy, open biopsy, wider excision, mastectomy) and considered 'necessary' or 'unnecessary' using final histopathological results as gold standard. RESULTS: In 170 patients, breast cancer was diagnosed. MRI detected 96% of multifocal disease and 95% of multicentric disease, whereas MX depicted 37 and 18%, and US 41 and 9% of them, respectively. All bilateral breast cancers were seen on MRI; both MX and US detected 56%. Findings of more extensive disease and unsuspected multiple breast cancer foci identified on MRI only, changed the therapeutic approach correctly in 30.6% of breast cancer patients. Nine unnecessary wider excisions and three unnecessary FNA/core biopsies were performed because MRI overestimated the number or size of malignant lesions. CONCLUSION: Preoperative breast MRI is an important adjunct to conventional imaging in the loco-regional staging of breast cancer and a useful tool in treatment planning.

Efficacy of sustained-release vaginal oestriol in alleviating urogenital and systemic climacteric complaints.

In a double-blind, placebo-controlled study, 109 patients suffering from local and vasomotor postmenopausal complaints were randomly assigned to treatment with either depot vaginal suppositories containing 3.5 mg oestriol (E3) or a placebo. The treatment schedule comprised one vaginal suppository twice weekly for 3 weeks initially, followed by maintenance therapy with one vaginal suppository weekly for the 6-month study period. The effectiveness of the therapy was assessed on the basis of questionnaires (Kupperman index for vasomotor complaints and an original urogenital index for local complaints) and gynaecological examinations which included assessments of vaginal cytology, vaginal pH and Döderlein bacilli. To rule out induced endometrial proliferation, endometrial biopsies were performed in 50 women before and after the study. The vaginal depot (E3) formulation showed highly significant superiority over the placebo with respect to therapeutic effect on local urogenital complaints and alleviation of vasomotor complaints, including hot flushes. Analysis of the endometrial biopsies indicated that the monotherapy used caused no endometrial stimulation. Taking into account the minimal rate of adverse effects, the 3.5 mg E3 depot formulation studied represents a useful variant in the range of preparations available for the treatment of post-menopausal complaints.

Carbohydrate metabolism during hormonal substitution therapy.

Oestrogens and progestogens are known to influence glucose tolerance. Impairment of glucose tolerance is seen in particular among users of progestogens with androgenic properties. Dydrogesterone is frequently used as the progestogen adjunct during oestrogen substitution therapy for the management of climacteric complaints in post-menopausal women. However, no detailed data have been published concerning its effects on carbohydrate metabolism. In this study, 20 healthy post-menopausal women received equine oestrogens at a dose of 0.625 mg/day for 2 mth, following which dydrogesterone was added cyclically (20 mg/day for 12 days/mth) over a period of 6 mth. Oral glucose tolerance tests were performed before and after each treatment regimen. In relation to the concentrations observed after oestrogen was given alone, dydrogesterone induced only a small increase in blood insulin values which was not statistically significant. The effect was similar to that produced by endogenous progesterone, which is known to be of no clinical significance.

Open prospective multicenter trial with a new monophasic contraceptive combination containing gestodene.

In a large and open prospective multicenter trial of 12,250 cycles from 2,378 women, contraceptive efficacy, clinical tolerance and acceptability of a new monophasic contraceptive combination containing 75 mcg gestodene (delta-5-levonorgestrel) and 30 mcg ethinyl oestradiol were studied. The objective was to assess efficacy, safety, side effects and cycle control of this oral contraceptive on healthy women using no other additional birth control methods. Two women became pregnant (0.016%) during the trial; both were patient failures. There was no effect on systolic or diastolic pressures. An average weight increase of 0.3 kg was noted. Cycle control was excellent with 95% of the cycles free of spotting and 98% free of breakthrough bleeding after six cycles. No serious complications occurred. There was an overall incidence of 14% reported side effects (after six cycles), indicating that the hormonal combination is well tolerated. It should be noted that 41.4% of the patients had some complaint before starting the treatment. For all complaints, a highly significant improvement was seen during the treatment.

PIP: In a large and open prospective multicenter trial of 12,250 cycles from 2378 women, contraceptive efficacy, clinical tolerance, and acceptability of a new monophasic oral contraceptive (OC) containing 75 mcg gestodene (delta-5-levonorgestrel) and 30 mcg ethinyl estradiol (EE) were studied. The objective was to assess efficacy, safety, side effects, and cycle control for this OC on healthy women using no other additional birth control methods. 2 women became pregnant (0.016%) during the trial; both were patient failures. There were no side effects on systolic or diastolic pressure. An average weight increase of 0.3 kg was noted. Cycle control was excellent with 95% of the cycles free of spotting and 98% free of breakthrough bleeding after 6 cycles. no serious complications occurred. There was an overall incidence of 14% who reported side effects after 6 cycles, indicating that the hormonal combination is well-tolerated. It should be noted that 41.4% of the patients had some complaint prior to the start of treatment. For all complaints, a highly significant improvement was seen during treatment.

Dimeric inhibin serum values as markers of ovarian activity in pill-free intervals.

Levels of inhibin A and B as well as other hormones in serum samples obtained during the pill-free interval in women taking combined oral contraceptives (OC) were measured to asses the extent of ovarian activity during that period. Type of pill and day of pill-free interval were recorded during routine gynecologic check-ups, if patients were in the pill-free period and had taken their pills regularly in the previous cycle. In addition to inhibin A and B, serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone were also quantified. Inhibin B levels rise significantly in parallel with rising levels of FSH, LH, and E2. Progesterone levels were completely suppressed and inhibin A levels rose slightly but insignificantly. Inhibins are sensitive biochemical markers of ovarian activity in pill-free intervals.

PIP: Serum values of dimeric inhibin A and B were measured to assess the restoration of pituitary and ovarian activity during the pill-free interval in women taking combined oral contraceptives. 175 healthy women 18-35 years of age from five areas in Belgium were enrolled and monitored during routine gynecologic examinations. During the 7 day pill-free interval, inhibin B levels rose significantly in parallel with rising levels of follicle-stimulating hormone, luteinizing hormone, and estradiol. Progesterone levels were completely suppressed. Inhibin A levels rose slightly but insignificantly, reflecting an absence of development of preovulatory follicles. These findings indicate that inhibins are sensitive biochemical markers of ovarian activity in pill-free intervals. Inhibin B appears to be predominantly a product of the cohort of developing primary and subsequent early antral follicles, while inhibin A secretion is more indicative of dominant follicular and corpus luteum function.

Intrauterine versus postnatal transport of the preterm infant: a short-distance experience.

AIM: The purpose of this study was to compare neonatal outcome (mortality, respiratory distress syndrome, intraventricular hemorrhage, necrotising enterocolitis, persisting ductus arteriosus, and septicaemia) after intrauterine transport versus neonatal transport in an area where short-distance transport is the rule. METHODS: The study was retrospective in nature. The files of all neonates delivered between 24 and 34 weeks from 1994 to 1998 and transported intrauterine or postnatally to the Antwerp University Hospital were reviewed. Cases of intrauterine fetal death and mothers discharged before delivery were excluded, as were infants with lethal congenital anomalies. RESULTS: A total of 328 deliveries after intrauterine transport, resulting in 416 neonates and 187 neonates transported postnatally were included. The maximum distance patients had to be transported was 40 km. Placental abruption was more frequent in the mothers of the neonatal transport group (13 vs. 5%, P=0.001). Corticosteroids were administered significantly less in the neonatal transport group (67 vs. 13%, P<0.0001). Preterm rupture of the membranes (36 vs. 20%, P<0.0001), preterm labour (73 vs. 36%, P<0.0001), and pre-eclampsia (10 vs. 7%, P<0.0001) were more frequent in the intrauterine transport group and this group had a lower mean birthweight and gestational age. There was no significant difference for overall neonatal mortality, respiratory distress syndrome, intraventricular hemorrhage, necrotising enterocolitis, persisting ductus arteriosus or septicaemia.

The role of the gynecologist in the diagnosis and management of breast disease.

As women depend on their gynecologist for advice regarding their reproductive organs, including the breasts, it is mandatory for the gynecologist to obtain extensive experience in diagnostic and management procedures of breast disease. Postgraduate teaching in breast disease should be integrated in the basic training schemes for all resident gynecologists/obstetricians. These teaching programs should include all aspects of diagnosis, management and follow-up of breast disease.

Laparoscopic tubal sterilization: postoperative follow-up and late gynecological complaints.

PIP: In a 7 year study, 322 women between 31-45 years old who submitted for laparoscopic tubal sterilization were questioned on specific gynecological complaints. 4 techniques including coagulation with tubal resection, double coagulation without resection, silastic rings, and spring-loaded clips were the surgical procedures used. After accounting for combination-pill use and abdominal complaints previous to sterilization, 7.1% of the women complained of menorrhagia, 6.2% complained of dysmenorrhea, and 8.7% complained of vague abdominal pain. The incidence of menorrhagia and dysmenorrhea occurred equally for each sterilization technique. Postoperative complaints may be due to hyperplasia of stroma with endometrial biopsies indicative of a persisting proliferation phase.^ieng

Amenorrhea, galactorrhea, hyperprolactinemia syndrome and breast carcinoma in a young woman.

A young female patient with amenorrhea, galactorrhea and hyperprolactinemia developed a carcinoma of the breast a few years later. Examination of the amenorrhea--galactorrhea syndrome did not reveal any prolactinoma so that hyperprolactinemia remains unexplained. Treatment with bromoergocryptine 5 mg daily was successful. The carcinoma was treated in the classic way by amputation of the breast, axillary curettage and adjuvant chemotherapy. However, the association of amenorrhea, galactorrhea and breast carcinoma via hyperprolactinemia raises the question of whether there is any etiologic--pathogenetic relationship. Convincing evidence of such a relationship has not been found in the literature.

Ovarian function in the non-mosaic Turner syndrome; a case report.

A 19-year-old girl, with the 45,XO non-mosaic Turner syndrome, presented having spontaneous regular menstrual activity. Hormonal analysis showed normal ovulatory cycles; histology of the ovaries demonstrated primary follicles. Nevertheless, the karyotype of the ovary and of the peripheral lymphocytes was pure 45,XO. Comment on ovarian function in the 45,XO karyotype is given.

The gonadotropin-resistant ovary syndrome in association with secondary amenorrhea.

A young patient with secondary amenorrhea and primary infertility is described. After a gynecological-endocrinological exploration including laparoscopy, the diagnosis indicates secondary hypergonadotropic, hypo-estrogenic normo-androgenic amenorrhea. The anatomopathological examination of an ovarian biopsy revealed an intact follicular apparatus, thus disproving the suspected diagnosis of climacterium praecox. Since very high gonadotropin doses could not induce an ovulation, it was concluded that the rare combination of secondary amenorrhea and the gonadotropin-resistant ovary syndrome must be present. The pathogenesis of this syndrome is discussed.

Dysgerminoma of the ovary in association with XY gonadal dysgenesis.

A case is reported of an adolescent presenting with primary amenorrhea. On pelvic examination a large unilateral ovarian tumor was palpated. Microscopic examination of the tumor removed at laparotomy revealed a pure dysgerminoma. Further gynecological-endocrinological investigations and chromosome analysis showed an XY gonadal dysgenesis. A review of current approaches to diagnosis, prognosis and especially to the controversial therapeutic modalities is presented.

Laparoscopic sterilization with electrocautery, silastic bands and spring-loaded clips: report of our experience with 790 patients.

A comparative study was carried out in 790 women undergoing one of the 3 most frequently used laparoscopic sterlization techniques: high-frequency unipolar electrocoagulation of the tubes, application of silastic rings or spring-loaded clips to the tubes. The technical problems and per- and postoperative (early) complications are assessed. The use of high-frequency unipolar current has been superseded by today's mechanical and non-electrical sterilization methods. The spring-loaded clip method appears to be a sterilization technique with a minimum of severe complications, and theoretically the greatest chances for possible refertilization.

PIP: In a 7-year comparative study, 790 women were sterilized using either high-frequency unipolar electrocoagulation with tubal transection (133 women) and double coagulation technique without cutting (350 women), silastic rings (142 women), or spring-loaded clips (165 women). Complications using the electrocoagulation technique include electrical shock, intra-abdominal burns, bleeding due to inadequate electrocoagulation, and coagulation necrosis of the skin. Bleeding occurred in the placement of silastic rings due to blood vessel damage with the sharp prongs of the ring applicator. Excessive traction with the clip applicator may cause bleeding during clip application. The clips and silastic rings also may drop in the Douglas' cul-de-sac but may be removed from the abdomen. 2 tubal pregnancies and 1 intrauterine pregnancy occurred using the electrocoagulation technique, 1 intrauterine pregnancy with the silastic ring technique, and 1 intrauterine pregnancy with the clip technique. Spring-loaded clips have few disadvantages but a hydrosalpinx or edomatously thickened tube are contraindications. In addition, the clip technique may be a method of possible refertilization.

Cesarean section for the second twin.

Using a case presentation, we would like to discuss the indications for abdominal delivery of the second twin following the vaginal delivery of the first. We would also like to review the risks of a twin pregnancy and the management of the delivery.