Norbert Lang

Epithelial Cells in Bone Marrow of Breast Cancer Patients at Time of Primary Surgery: Clinical Outcome During Long-Term Follow-Up

PURPOSE To evaluate the detection of epithelial cells in bone marrow of breast cancer patients as an indicator of metastatic disease. PATIENTS AND METHODS Between 1989 and 1994, bone marrow biopsies were performed on 393 breast cancer patients during primary surgery. Specimens were stained immunocytochemically for epithelial cells expressing cytokeratins or the epithelial membrane antigen. The long-term outcomes of these patients were analyzed in this study. RESULTS In 166 of 393 patients, epithelial cells were found in bone marrow (BM) aspirates. These patients were designated BM+. The rate of tumor recurrence or cancer-related death was significantly higher in BM+ patients than in BM- patients. Multivariate analysis using the Cox regression model revealed BM status as a prognostic parameter independent of tumor size and axillary lymph node status. However, tumor size and axillary lymph node status were clearly superior prognostic parameters. CONCLUSION Disseminated epithelial cells in BM are associated with poor clinical outcome in breast cancer patients. However, the presence of these cells is not a sufficient parameter to predict growing metastases in the majority of patients, suggesting that epithelial cells in the BM of breast cancer patients at the time of surgery have limited metastatic potential. The role of these cells needs to be further evaluated.

Intrauterine Treatment of Fetal Goitrous Hypothyroidism Controlled by Determination of Thyroid-Stimulating Hormone in Fetal Serum

We report a rare case of fetal goitrous hypothyroidism complicated by polyhydramnios and preterm labor in a mother without thyroid gland pathology. The diagnosis was made in the 26th week by ultrasound and cordocentesis [TSH 170 µU/ml, free T4 0.2 ng/dl]. The therapeutic regime required repeated fetal blood sampling for determination of thyroid hormones. Five intra-amniotic administrations of 250 µg levothyroxine (LT4) weekyl were initiated. Because of the persisting goiter and the elevated level of TSH (128 µU/ml in 32 weeks) in the fetal serum the dosage had to be adjusted to 500 µg LT4 in the next five injections. TSH in fetal serum declined to 49.2 µU/ml in 36 weeks. Normal fetal growth and an uncomplicated course of pregnancy between the 27th and 37th week of gestation were observed. Monitoring of intrauterine therapy by determination of TSH in fetal serum may provide more reliable data than measuring TSH in amniotic fluid. A review of 15 cases of fetal goitrous hypothyroidism in the English literature is presented.

CA-125 serum concentrations during the menstrual cycle

CA-125 is an antigenic determinant expressed on ovarian cancer cells and serves as serum marker in patients with ovarian cancer. It has also been detected, however, in serum of healthy women and in patients with benign gynecologic diseases. Previous studies in patients with ovarian hyperstimulation syndrome suggested that the production of CA-125 is correlated with proliferative ovarian activity. In this study, we describe the pattern of CA-125 secretion in 13 healthy women during menstrual cycle and during hormonal contraceptive treatment. That pattern is characterized by an increase of CA-125 serum concentrations parallel to the growth of the dominant follicle. It was not observed during hormonal contraceptive treatment. We conclude that CA-125 serum levels during menstrual cycle seem to be dependent upon the cyclic changes in the female genital tract.

Tumor Size, Axillary Lymph Node Status and Steroid Receptor Expression in Breast Cancer: Prognostic Relevance 5 Years after Surgery

Tumor size, axillary lymph node status and expression of steroid receptors are well-established prognostic factors in breast cancer. However, it is not clear if these prognostic factors are time-dependent variables and lose their significance after several years of disease-free survival. To analyse how long these factors keep their prognostic relevance survival of 1162 breast cancer patients was analysed retrospectively. The post-operative follow-up period was split into consecutive 2-year intervals and each interval was analysed for rate of recurrence and rate of tumor depending deaths. Furthermore, a multivariate analysis was performed for the total follow-up time and for the follow-up period starting 5 years after surgery. Multivariate analysis revealed tumor size, axillary lymph node status and estrogen receptor status as independent prognostic parameters. Analysing separately the rate of recurrences and tumor-related deaths during consecutive 2-year intervals, only the tumor size was a constant prognostic parameter, whereas prognostic relevance of lymph node status decreased. Estrogen receptor status associated with favourable prognosis during the first years after surgery changed to an unfavourable prognostic factor 4 years after surgery. To summarize, prognostic factors obtained at the time of surgery can lose their significance with increasing disease-free survival.

Comparison of GnRH agonists and antagonists in unselected IVF/ICSI patients treated with different controlled ovarian hyperstimulation protocols: a matched study

OBJECTIVES To evaluate the results of the use of GnRH antagonist (GnRHant) and GnRH analog (GnRHa) in two matched groups of unselected IVF/ICSI patients in a retrospective matched pair analysis. STUDY DESIGN Patients (n=52) were stimulated with human menopausal gonadotropin (hMG) and/or recombinant FSH (rFSH). In Group I (n=26) a daily dose of 0.25mg of Cetrorelix (GnRHant) was administered when follicles reached a diameter of > or = 14 mm. Patients in Group II (n=26) were first desensitized with GnRHa triptorelin long protocol, which was continued during the gonadotropins treatment until the induction of ovulation. RESULTS In both groups, serum LH levels remained low during the stimulation. The mean length of stimulation, and the dose of FSH required per patient were similar in both groups. The mean E2 level on day of hCG administration was significantly higher in the patients of Group II (2076+/-1430 versus 1145+/-605 pg/ml), however, a progressive increase in serum E2 concentration during the cycle was noted in both groups. A median of 5.38 and 6.34 mature oocytes per patient was obtained, and the fertilization rate was 59.3% in Group I and 63.6% in Group II. Pregnancy rate (PR) were better in Group II (15 versus 5%), and no severe or moderate ovarian hyperstimulation syndrome (OHSS) occurred. CONCLUSIONS GnRHant and GnRHa provide comparable results in unselected patients, while GnRHant allows a higher flexibility in the treatment.

Zweizeitige Geburt bei extremer Frühgeburtlichkeit des ersten Mehrlings: Bericht von 3 Fällen

Fragestellung: Die extreme Fruhgeburtlichkeit in einem Schwangerschaftsalter zwischen 23 und 26 Wochen ist mit einer hohen perinatalen Mortalitat und Morbiditat verbunden. Ein aktives, schwangerschaftsprolongierendes Vorgehen nach der unaufhaltsamen Geburt des ersten Feten bei einer Mehrlingsschwangerschaft konnte in diesem Schwangerschaftsalter wertvolle Zeit fur die in utero verbliebenen Feten gewinnen. Patientinnen und Methodik: Bei drei Mehrlingsschwangerschaften (einmal Zwillinge, zweimal Drillinge) kam es in der 23 + 2, 24 + 2 und 24 + 7 Schwangerschaftswoche zur Spontangeburt des ersten Mehrlings. Nach der Geburt dieses Kindes wurde die Nabelschnur ligiert, eine Cerclage in der Technik nach McDonald angelegt sowie eine peri- und postoperative Tokolyse und Antibiose verabreicht. Ergebnisse: Bei zwei Schwangerschaften (einmal Drillinge, einmal Zwillinge) gelang eine Verlangerung der Schwangerschaft um 22 bzw. 70 Tage. Vier der funf Kinder uberlebten. Der Wochenbettverlauf dieser Mutter war unauffallig. Bei der dritten Schwangerschaft (Drillinge) kam es am Tag der Geburt des ersten Kindes zu einer Amnioninfektion. Das erste, spontan geborene Kind uberlebte; die am Tag danach durch Sektio entbundenen Kinder verstarben. Die Mutter erlitt im Wochenbett eine Sepsis aufgrund einer infizierten Ovarialvenenthrombose. Schlusfolgerung: Die Prolongation einer Mehrlingsschwangerschaft nach der Geburt des ersten Kindes in einem Schwangerschaftsalter von 23 bis 26 Wochen ist in gewissen Fallen eine erfolgversprechende Masnahme, um die Reife der intrauterin verbliebenen Feten zu erhohen. Dieser Vorteil mus gegen die negativen Auswirkungen einer moglicherweise auftretenden Amnioninfektion abgewogen werden. Objective: Extreme immaturity between 23 and 26 weeks of gestation is associated with high neonatal mortality and morbidity. The Prolongation of multifetal gestations after the delivery of the first fetus might achieve a gestational age for the remaining fetus(es) more compatible with neonatal survival. Study design: In three twin and triplet pregnancies the first fetus was born at a gestational age of 23 + 2, 24 + 2 and 24 + 7 weeks. We used cervical cerclage, tocolysis and antibiotic therapy to extend the intrauterine life of the remaining fetus(es). Results: In two pregnancies (triamniotic, trichorionic triplets and biamniotic, monochorionic twins) we succeeded in prolonging the gestation of the in utero remaining fetus(es) for 22 and 70 days. Only the first born fetus with a gestational age of 23 + 2 weeks died, the other four neonates survived. No maternal complications occurred in these two patients. In the third pregnancy (triamniotic, trichorionic triplets) chorioamnionitis was the reason for a Caesarean section one day after the spontaneous delivery of the first fetus. The first fetus survived while the other two died. The mother developed septicaemia due to a infectious ovarian vein thrombosis. Conclusion: Delayed delivery in multifetal pregnancies with extreme immaturity of the first fetus might be a reasonable option in some pregnancies to enhance maturity of the in utero remaining fetuses. This advantage must be weighed up against the risk of severe chorioamnionitis seen in one patient in our series.

CEA und CA 15-3 beim Mammakarzinom : Ihre Bedeutung für die Diagnose von Primärtumoren, Lokalrezidiven und Fernmetastasen

Their Importance in Diagnosis of Primary Tumours, Local and Distant Recurrences: The dependence of CEA- and CA 15-3-serum concentrations on histopathological criteria and the role of serum measurements during follow-up of breast cancer is controversially discussed. The manuscript summarises the experience gained with serial CEA and CA 15-3 measurements in 7617 patients with benign and malignant tumours of the breast from primary surgery and during follow-up. It could be shown that the serum concentrations of both glycoproteins were different in benign and malignant tumours at the time of diagnosis. These differences were caused by patients with distant metastases. When these patients were excluded, the distribution of serum concentrations of both glycoproteins did not depend on tumour size, number of lymph node metastases, hormonal receptor content of the tumour and menopausal status. In contrast, 89% of all patients with elevated CEA and/or CA 15-3 serum concentrations and a continuous increase developed distant metastases immediately or within 12 months. In 23 (6%) patients secondary malignancies could be diagnosed and in 20 (5%) patients an increase in the concentrations was observed which was not followed by distant metastases or secondary malignancies (in these patients the levels dropped back to the normal range within 3 months). These data clearly indicate that measurement of CEA and CA 15-3 in serum is an objective method for the early detection of distant metastases in breast cancer patients.

Nachweis von Insulin-Rezeptoren (IR) in Ovarialkarzinomgewebe

Der Tumormarker CA-125, ein hochmolekulares Glykoprotein, hat sich als verlaslicher Parameter von Ovarialkarzinomen erwiesen.