Topotecan chemotherapy in patients with breast cancer and brain metastases: results of a pilot study.

BACKGROUND: Symptomatic brain metastases occur in approximately 10-15% of patients suffering from breast cancer and are linked to a clear deterioration of the patient's condition. Although radiotherapy is recommended as a primary therapy, the optimal management remains controversial. To evaluate the role of topotecan as a primary chemotherapy for brain metastases, we performed a pilot study in patients with metastatic breast cancer. PATIENTS AND METHODS: 24 patients with newly diagnosed, bidimensionally measurable brain metastases received topotecan, 1.5 mg/m(2) day, 30-min infusion for 5 days every 3 weeks. A total of 93 courses of therapy were administered (range 1-11, median 3 courses per patient). Prior radiotherapy was excluded. Most of the patients had received prior adjuvant or palliative chemotherapy. RESULTS: 3/24 patients were withdrawn from the study for various reasons, 16/24 patients could be evaluated in terms of their response to therapy; 1 and 5 patients showed complete and partial response to therapy, respectively, and 5 patients had a stable condition. The median time of survival was 6.25 months. Hematologic toxicity was the major side effect, nonhematologic side effects occurred rarely and were tolerable. CONCLUSIONS: Our results demonstrate that primary chemotherapy with topotecan is an effective and well-tolerated treatment for patients with breast cancer and CNS metastases. Based on this pilot study, future clinical protocols should be developed including multimodal treatment strategies (i.e. radiotherapy).

[Is there a correlation between tubal occlusions in chronic salpingitis and urogenital chlamydia infections?]. / Gibt es einen Zusammenhang zwischen Tubenverschlüssen bei chronischer Salpingitis und urogenitalen Chlamydieninfektionen?

A prospective study was performed to analyse the relationship between urogenital infections caused by Chlamydia trachomatis and occlusions of the fallopian tubes with histologically confirmed chronic salpingitis and salpingitis isthmica nodosa. 110 infertile patients were tested for C. trachomatis infection. 23 patients with tubal occlusions and histologically confirmed chronic salpingitis (group 1) and eight patients with salpingitis isthmica nodosa (group 2) were compared to 13 patients with tubal occlusions after tuboligation (group 3), and to 66 patients with patent fallopian tubes as demonstrated by laparoscopy or hysterosalpingography (group 4). The prevalence of infections of the endocervix or urethra and the presence of Chlamydia in urine was low in all four groups. However, in groups 1 and 2, the median Chlamydia IgG and IgA serum antibody titres were significantly higher (p < or = 0.0002) than in groups 3 and 4. This result illustrates the association between urogenital infections with Chlamydia and tubal occlusions with histologically documented chronic salpingitis and salpingitis isthmica nodosa.

Embryonic losses after in vitro fertilization and embryo transfer.

Early loss of embryos is a major problem after in vitro fertilization (IVF) and embryo transfer (ET). Because implantation of the embryo is a precondition for an increasing serum beta-hCG level, the embryonic development cannot be evaluated during the pre- and peri-implantation period. Early pregnancy factor (EPF) is a marker of the development of the embryo before and during implantation. Therefore serum samples of 82 patients were screened for EPF and beta-hCG after IVF/ET. 63% (52/82) of all patients were positive for EPF, 21% (17/82) showed elevated serum beta-hCG levels. Clinical pregnancies occurred in 12 patients (15%) resulting in nine deliveries. After difficult ET EPF turned negative more frequently in the peri-implantation period compared to transfers without problems. Emphasis should be directed towards optimizing the placement of the embryos and towards minimizing the trauma of the uterus.

[Doppler ultrasound in monitoring twin pregnancies with early discordant growth]. / Dopplersonographie zur Uberwachung von Zwillingsschwangerschaften mit frühzeitigem diskordanten Wachstum.

Early growth retardation in one twin is complicated by a high fetal mortality and morbidity. It is often very difficult to determine the optimum time of delivery in regard to placental insufficiency and prematurity. We report of two cases in which doppler velocimetry was a helpful method in monitoring those pregnancies at high risk. A growth retardation of three weeks was found in one child of a twin pregnancy at 17 weeks of gestation. Doppler velocimetry at 23 weeks showed a reverse flow and centralisation and the child died at 27 weeks. The other twin then also developed pathologic flow patterns and had to be delivered by cesarean section. In the second patient, pregnancy could be continued in spite of a growth retardation of three weeks in one child at 15 weeks and an additional decrease in the growth rate of both children from 30 weeks onwards. Cesarean section had to be performed at 34 weeks because of premature rupture of membranes.

[Rate of early abortion after in vitro fertilization and embryo transfer]. / Frühstabortrate nach In-vitro-Fertilisation und Embryotransfer.

The high rate of implantation failures in infertile patients after in vitro fertilization must be regarded as the major problem of the kind of treatment. Usually, no information on the development of the embryo can be obtained for the time between embryo replacement and rising beta-hCG levels. Own studies on the early pregnancy factor (EPF) showed a positive reaction few hours following the contact of a fertilized oocyte with the endometrial surface. Therefore, we used the EPF as a marker for the viability of the embryo in 82 patients after in vitro fertilization and embryo transfer. Within two days after embryo transfer the EPF was positive in 52 (63%) patients and negative in 30 (37%) patients. In these women the embryos may have been lost during handling or may have discontinued further development. Between day 3 and day 12 after transfer the EPF turned to negative values in 35 patients--especially between day 6 and 10. These cases must be regarded as true implantation failures. After day 12 following embryo transfer, rising beta-hCG levels could be measured in 17 women (21%), but only in 12 patients (15%) could a growing embryonic sac be detected by ultrasound. From these figures, we may conclude, that about half of the embryos are lost already during the step of embryo transfer and the other half during implantation. Therefore, more attention should be given to the handling of the embryos to increase the pregnancy rate after in vitro fertilization.

[Glassy cell carcinoma of the cervix]. / "Glassy cell carcinoma" der Zervix.

Glassy cell carcinoma of the cervix is a rare carcinoma with rapid progression and early metastasis. The aggressive course of a glassy cell carcinoma of the cervix in Stage Ib (FIGO) of a 24-year-old woman could neither be markedly influenced by radical hysterectomy, nor by chemotherapy and radiation. The patient died ten months after diagnosis.

[Successful prevention of adhesions using peat and humic acids]. / Erfolgreiche Adhäsionsprophylaxe durch Anwendung von Moor und Huminsäuren.

In order to verify the adhesion preventing capability of peat and peat components, 180 female rats were subjected to therapeutic bathing after standardised lesions had been placed on both uterine horns and the peritoneum of the anterior abdominal wall. From the 3rd and 7th day after surgery, respectively, randomized groups of animals consisting of 20 animals each were bathed in tap water, pure fresh peat, peat solution after pressing, centrifugation and filtration, and a solution of humic acids extracted from peat, all at the same temperature. One week after bathing for three weeks, the rats were relaparotomized, and quality and degree of the adhesions found were documented. Significant less and minor (p less than 0.001) adhesions were found in animals bathed in humic acid solution compared to the animals which had not been bathed at all. Peat solution and fresh peat reduced the formation of adhesions significantly, too, while warm water baths did not show any antiadhesive effect. Our results suggest humic acids to be the most effective component of peat with regard to the prevention of adhesions.

[Spermatozoal antibodies in cervical mucus and in the luminal fluid of the uterus in sterile patients]. / Spermatozoen-Antikörper im zervikalen Mukus und in der luminalen Flüssigkeit des Uterus bei Sterilitätspatientinnen.

Poor postcoital tests in infertile patients may be due to dysmucurrhoea, low sperm count, or specific antibodies against spermatozoa. Using a latex agglutination test ("Sperm-antibody-slide-test", Fa. Biotec, Hannover), we examined the cervical and uterine secretions of the patients for sperm antibodies. The results showed a close correlation between a positive sperm-antibody-test and a poor postcoital test, especially in those couples with regular sperm quality. Also in cases with normal postcoital tests, positive sperm-antibody titers can be observed. Therefore, the sperm-antibodies may disturb fertilization in infertile patients even without causing immobilization or agglutination of the spermatozoa in the female genital tract fluids. The determination of the spermatozoa-antibody content in the cervical and uterine secretions must be regarded as an improvement in the diagnostic procedure in human infertility.

[The diuretic effect of a bath. Study in healthy pregnant females and patients with edema and gestosis]. / Die "ausschwemmende" Wirkung des Bades. Untersuchung an gesunden Schwangeren und Patienten mit Odemen bzw. Gestose.

The effect of a 40 minute thermoneutral bath on diuretic function and blood volume in a total of 27 pregnant women (13 healthy and 14 pregnant women with edema rsep. EPH-gestosis) was investigated. In both groups water immersion led to a significant increase of urine flow, natriuresis, kaliuresis, osmotic and free water clearance. Plasma volume increased about 8-9%. The patients with gestosis showed a higher creatinine clearance. The same group also showed a higher osmotic clearance and relatively more sodium excretion. Regarding the flushing effect of bath, two mechanism of water immersion that originated in hydrostatic pressure have to be discussed-activation of renal functions and mobilisation of interstitial fluid.

[Premature rupture of fetal membranes near term: wait it out or intervene?]. / Vorzeitiger Blasensprung in Terminnähe: Abwarten oder handeln?

In the here presented study we investigated whether it is preferable to wait or to intervene after premature rupture of membranes (PROM) near term (greater than or equal to 36 weeks). In our first approach to answer this question we compared two time periods retrospectively in which we had managed PROM in alternate ways: In 1984 we waited 12 hours for spontaneous start of labor. After 12 hours we induced labor by Oxytocin infusion. In 1986 and 1987 we applicated 0.4 mg Prostaglandin E2 (PGE2) intracervically instead of iv Oxytocin. 67 patients received PGE2 within 6 hours, 63 patients within 7-12 hours after PROM. In total we included 416 patients into this study. We were able to show that intracervical PGE2 gel gave unambiguously better results both for primiparae and multiparae. We observed the least complications with early (less than or equal to 6 h after PROM) application of PGE2 gel. The following parameters favoured early PGE2 application significantly (p less than 0.01): interval PROM - delivery, duration of labor, incidence of cesarean sections, morbidity rate of mother and child. In our second approach we were able to confirm our results in a randomised prospective study, in which we looked at 57 women with PROM in early 1988. Additionally a direct correlation of time between PROM and birth and rate of maternal or neonatal infection emerged: We saw the best results, if labor started within 6 hours after PROM. The rate of cesarean sections and newborns that had to be transferred to pediatrics had doubled within 7-12 hours and more than quadrupled after 12 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

[Tubal pregnancies: early pregnancy factor, progesterone, beta-HCG and vaginal sonography as differential diagnostic parameters]. / Tubargraviditäten: early pregnancy factor, Progesteron, beta-HCG und Vaginalsonographie als differentialdiagnostische Parameter.

By anamnestic, clinical, biochemical (beta-HCG), and ultrasonographical data, only a portion of ectopic pregnancies can be diagnosed early enough to allow conservative surgery. In the present study, the diagnostic value of the Early Pregnancy Factor (EPF), progesterone, and endosonography was investigated in 142 patients with suspected tubal pregnancy. beta-HCG and Progesterone serum levels had been in the lover range of or below normal values in most cases of tubal pregnancy compared to intrauterine pregnancies. The EPF was found to be negative in 94% of all cases of ectopic or disturbed intrauterine pregnancies, while all these patients showed a positive pregnancy test (HCG). By abdominal ultrasonography, only 73.7% of all tubal pregnancies could be detected, while transvaginal scanning increased the rate of verified diagnoses up to 90.6% of these cases. Our results suggest that EPF measurement and endosonography are valuable supplements for precise and rapid diagnosis of ectopic pregnancies.

[Early abortion rate in sterility patients: early pregnancy factor as a parameter]. / Untersuchungen zur Frühstabortrate bei Sterilitätspatientinnen: EPF als Parameter.

To evaluate the diagnostic value of Early Pregnancy Factor (EPF) measurements in infertile patients, we performed a modified rosette inhibition test in 58 women after follicular stimulation and/or homologous artificial insemination (AIH). The patients were grouped according to the main diagnosis as cervical hostility, poor semen quality, and anovulation. While the overall fertilization rate in our patients was 39.6%, which is considerably lower than in comparable studies of fertile women, the pregnancy rates per EPF positive cycle in the various groups were 25.0%, 30.8%, and 50.5%, respectively. As the process of fertilization can be detected by EPF measurement within 48 h after ovulation, a distinction can be made between failure of fertilization and of implantation. Thus, a valuable diagnostic tool has become available for treatment of infertile patients.

Early pregnancy factor as a marker for the earliest stages of pregnancy in infertile women.

Early pregnancy factor (EPF) is known to be detectable in sera of pregnant women within 24 to 48 h after conception. To examine the incidence of early embryonic loss after hormonal treatment and homologous artificial insemination, we screened the sera of our patients for the presence of EPF by means of a rosette inhibition test. Our results show a considerably lower conception rate as described in appropriate studies on fertile women. If reduced sperm quality is the indication for insemination, the abortion rate in the first 2 weeks of gestation is significantly increased in relation to the rest of our patients. Infertility because of an impaired development of the embryo, especially if repeated EPF-positive cycles do not result in a pregnancy, may be due to chromosomal defects or malformations and a chromosomal analysis is recommended. In patients in whom EPF is never found to be positive, indicating a disorder of conception, we regard IVF/ET to be the treatment of choice.

[The fetal condition during the mother's baths--studies using underwater cardiotocography in pregnancy and labor]. / Das fetale Befinden während eines Bades der Mutter--Untersuchungen mit Hilfe der Unterwasserkardiotokographie in der Schwangerschaft und unter der Geburt.

The effect of warm baths (34-38 degrees C) during pregnancy was studied in 41 patients between 30 and 35 weeks of gestation. The focus of our interest deals with the influence of bathing on the unborn child and physiologic changes in the mother. Continuous CTG monitoring was guaranteed by water-proofed and isolated transducers in connection with telemetry. During the bath, we found a significant increase of registered accelerations due to more frequent fetal body movements. There were no decelerations. A positive effect on the perfusion of the feto-placental unit can be assumed resulting from a significantly higher maternal blood pressure amplitude. Due to an increased diuresis, the average weight loss amounted to 300 g. Subaqua CTG monitoring was used as well in 122 patients who took a bath in the initial period of delivery, 30 of whom after rupture of the membranes. In very few cases (5% and 12% after rupture of the membranes, respectively), we found a slight worsening in the CTG which turned out to be reversible after the bath. There were no pathologic CTG patterns. After bathing, women with early rupture of the membranes showed a significantly lower rate of positive infection parameters than women in a control group who had no bath during the first stage of delivery (13% versus 40%). This fact may be correlated to the duration of delivery which decreased from 17h 10 min to 12th 50 min on average after bathing.

[Vulvar cancer in a 13-year-old girl]. / Vulvakarzinom bei einem 13jährigen Mädchen.

A case of squamous cell carcinoma of the vulva in a 13-year old girl is reported. The disease progressed inspite of radiotherapy and the patient died five months later. In the past 115 years only 35 malignomas of the vulva in children and adolescents have been reported, including our case. Most tumours were either of embryonic origin or sarcomas.