[Advanced ectopic pregnancy--clinical management]. / Fortgeschrittene Extrauteringravidität - klinisches Management anhand einer Fallbeschreibung.

Advanced ectopic pregnancy - clinical management. In case of vaginal bleeding and diffuse abdominal pain you have to include the diagnose of (rare) advanced ectopic pregnancy. Even with ultrasound technique in some of the cases you need further examinations to be sure with your diagnose. Because of the high incidence of maternal morbidity the treatment ist immediate primary laparotomy. In some pregnancies after the 23/24 week there is possibility of a more conservative approach. We describe a case with immediate operative intervention.

[Angiosarcoma of the breast after conservatively operated breast carcinoma--a sequela of adjuvant radiotherapy?]. / Das Angiosarkom der Brust nach konservierend operiertem Mammakarzinom--eine Folge der adjuvanten Nachbestrahlung?

Angiosarcoma represents only 2.4% of soft tissue malignancies. Primary angiosarcoma of the breast is also a rare neoplasm. The incidence of this disease has been reported to be 0.04% of all breast malignancies. The aetiology is unknown. Angiosarcoma associated with chronic lymphoedematous arm of a postmastectomy woman was described by Stewart and Treves. In this paper we describe a 62-year-old female who underwent wide excision, axillary node dissection and adjuvant radiotherapy for primary breast cancer. After 5 years she noticed a purple discolouration of the treated left breast. Biopsy of these areas confirmed an angiosarcoma. No haematogenous dissemination was found. She underwent simple mastectomy without systemic therapy. A chest X-ray 3 months later revealed diffuse bilateral lung metastases. The incidence of breast conserving therapies is growing fast. Until now we have no evidence on the role of irradiation as an aetiological reason for angiosarcoma after breast-conserving surgery and axillary node dissection. Therefore, we have to pay increasing attention to these patients. A patient with history of radiotherapy after breast conserving therapy and skin discolouration must undergo a biopsy of these areas. The only therapy of angiosarcoma is an early mastectomy. The success of chemotherapy is uncertain. Possibly adjuvant chemotherapy with actinomycin D for the group with poorly differentiated tumours appears beneficial. Prospective studies might help to resolve this question.

Two human breast cancer cell lines showing decreasing telomeric repeat length during early in vitro passaging.

Specific DNA repeats serve as a molecular protection shield at the telomeric ends of mammalian chromosomes. The absence of telomerase activity leads to a gradual decrease of telomeric repeat length in normal somatic cells. In contrast, immortalized cells from malignant tumors are usually thought to re-express telomerase to overcome a self-limited growth. Following this hypothesis, re-expression of telomerase is due to a rare mutational event. Herein we describe our results of telomeric length determination in two newly established breast cancer cell lines. During in vitro establishment from pleural effusions, both cell lines showed a marked decrease of the upper border range of telomeric repeat length distribution. The lower border remained within a constant range characteristic for each cell line. In no case was decrease of repeat length accompanied by an increased incidence of telomeric associations or fusions. The results show that a constant telomeric repeat length does not constitute a characteristic feature of immortalized cells. Furthermore, the kinetics of repeat length decrease and the constant range of the lower border reveal that the onset of telomerase activity is not necessarily due to a rare, i.e., mutational, event.

Adjuvant randomized trials of doxorubicin/cyclophosphamide versus doxorubicin/cyclophosphamide/tamoxifen and CMF chemotherapy versus tamoxifen in women with node-positive breast cancer.

PURPOSE: We report two randomized trials of adjuvant systemic therapy in 747 patients < or = 65 years of age with histologically proven node-positive breast cancer. PATIENTS AND METHODS: Patients were selected for the two trials on the basis of lymph node and hormone receptor status. The only stratification was based on the treating institution. In patients with a lower probability of recurrence (n = 276), a comparison between endocrine therapy (tamoxifen [Tam] 30 mg/d for 2 years) and chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF] intravenously [IV], six cycles every 4 weeks) was performed. In patients with a higher risk of recurrence (n = 471), a comparison between chemotherapy alone (doxorubicin plus cyclophosphamide [AC] i.v., eight cycles every 3 weeks) and the same chemotherapy plus Tam was made. RESULTS: Overall, we found that CMF and Tam are equally effective in a subgroup of patients with a relatively good prognosis (low-risk patients). However, in the subset of women < or = 49 years old, a significantly greater disease-free survival (DFS) rate (P = .01) and overall survival (OS) rate (P = .002) was observed following therapy with CMF compared with Tam. In patients > or = 50 years old, the opposite was found, and Tam appeared to be superior to CMF (DFS, P = .003; OSm P = .5). These results must be interpreted cautiously, since a post-hoc stratification of patients by age (< or = 49, > or = 50) was performed, and significantly more younger, low-risk patients were randomized to receive chemotherapy alone and more older patients to receive Tam alone. Among patients with a relatively poor prognosis (high-risk patients), a combination of AC plus Tam was equivalent to AC and, when women were analyzed by age, this was found to be true of patients < or = 49 years as well. However, the addition of Tam to AC in women age > or 50 years resulted in a statistically significantly higher DFS (P = .01) and a trend toward better OS compared with women who received AC alone. CONCLUSION: Further trials are required to analyze the role of combined simultaneous or sequential chemoendocrine adjuvant treatment or each single therapy alone in defined risk-adapted subsets of node-negative and node-positive patients.

Effects of tamoxifen on human breast cancer cells in vitro.

Long-term treatment of the estrogen sensitive human breast cancer cell line EFM-19 with the antiestrogenic compound Tamoxifen resulted in a variant line EFM-19 T, which was stimulated by Tamoxifen. Estrogen receptor analysis by radioligand assay (charcoal method), revealed a 2.5 fold higher receptor concentration in EF-19 T cells than in the parental EFM-19 cell-line. As demonstrated with the immunocytochemical assay (ER-ICA) only 60% of the parental EFM-19 cells were estrogen receptor positive, whereas 98% of the EFM-19 T cells expressed estrogen receptor protein. In addition, receptor content per cell was higher in the Tamoxifen treated subline than in the parental cell line. Analogous with the growth promoting effect of Tamoxifen on EFM-19 T cells, Tamoxifen acted like estrogen leading to a down regulation of cellular estrogen receptor concentration. The partial growth dependency of the EFM-19 T cells on the presence of Tamoxifen demonstrates estrogenic effects of Tamoxifen and explains the withdrawal response obtained in the treatment of breast cancer patients when remission occurs after termination of ineffective treatment with Tamoxifen.

[Subjective stress of adjuvant chemotherapy in breast cancer patients]. / Subjektive Belastung einer adjuvanten Chemotherapie bei Mammakarzinom-Patientinnen.

50 patients, suffering from carcinoma of the breast pT1-3 with concomitant metastatic affection of the lymph nodes with no evidence of distant metastases, and who received adjuvant chemotherapy (either CMF od AC/EC) were examined. Somatic and psychic interferences, the feeling of well-being and general condition, as well as a critical estimation of the clinical situation were assessed. Besides nausea and vomiting, and still prior to hair fall out, chemotherapy activated the memory of the carcinoma. 92% of the patients agreeing to chemotherapy described their decision as having been based exclusively on the medical information. Nevertheless, 30% feel insufficiently informed, so the fear of side effects, the waiting period prior to application, and the confrontation with the seriously ill, were described as a negative experience. An optimistic view with respect to improving the prognosis of the disease were correlated with chemotherapy: 74% would agree to a further chemotherapy. Psychic abnormalities, e.g. depressions, could not be shown following chemotherapy when compared to a reference population.

[Diagnostic predictive value of C-reactive protein and expectant management of patients with premature rupture of the membranes]. / Diagnostische Aussagekraft von C-reaktivem Protein und exspektatives Management bei Patientinnen mit vorzeitigem Blasensprung.

To evaluate the predictive diagnostic value of CRP in a wait-and-see management of PROM 110 courses of labour and childbed with 114 babies were investigated with respect to both complications of mother and newborn. Complications during childbed could only be seen in 2.7%, 3.4% of the newborns suffered from septic disease. With regard to complications of newborns and mothers mediated by infection, CRP was demonstrated to have a prepartum sensitivity of 79% in combination with a specificity of 80%. The absolute highest sensitivity and specificity of CRP were found at a cut-off point of about 14 mg/l, which is clearly above the normal level of 6 mg/l serum. In almost 50% of the cases with maternal antepartum CRP levels up to 20 mg/l no pathogenic bacterial invasion could be revealed in the newborn. CRP therefore can be taken as an additional parameter in the management of PROM even in cases treated with corticosteroids due to its specificity and indicates better than WBC and polys when to terminate the wait-and-see attitude.

[Secretory breast cancer. A special morphologic entity, especially in children and young females]. / Das sekretorische Mammakarzinom. Eine besondere morphologische Entität, vorwiegend bei Kindern und jungen Frauen.

We are reporting a rare case of secretory breast cancer with axillary node involvement in a 16-year-old patient. Symptomatic systemic spread occured unusually early during adjuvant chemotherapy, suggesting primary resistance of the tumour to chemotherapy. We are unaware of any such case reports published world wide. Due to the small number of similar case reports in the literature, the natural history of this type of cancer remains uncertain, offering no development of firm treatment guidelines.

[Locoregional breast cancer recurrence. Treatment following exclusively local therapy]. / Lokoregionäres Mammakarzinomrezidiv. Behandlung nach ausschliesslicher lokaler Therapie.

In 58 out of 515 patients with a primary carcinoma of the breast there was local-regional recurrence. Treatment consisted in generous excision and local radiation (50-60 Gy). After a mean observation period of 65.4 +/- 22.2 months, distant metastasization was found to have occurred in 22 patients (37.9%). Of the other 36 patients 23 (39.7%) had suffered no further recurrence at the end of this time, while 13 patients (22.4%) had a new local-regional recurrence. In a retrospective study a variety of parameters of prognosis were investigated in order to determine to their predictive value. It was found that there were significant differences in overall survival rates with tumors of histological differentiation stage I as compared to tumors of differentiation stages II and III (p = 0.003). There were no differences in the recurrence-free interval (p = 0.34). The presence or respectively lack of steroid receptors in the primary tumor made no significant differences to the recurrence-free interval and the survival rates. Those of the patients on whom this study was based whose axillary nodal status was N+ had received (adjuvant) treatment with cytostatics. This resulted in no differences in the recurrence-free interval (p = 0.28) or the overall survival rates (p = 0.3) when the N+ and N- patients were compared. The therapeutic conclusion drawn from these results is that breast carcinoma patients with an exclusively local-regional recurrence should initially receive local treatment only; systemic therapy should be reserved for the generalization stage.

[Importance of clinically prognostic factors in the treatment of advanced ovarian carcinoma]. / Die Bedeutung klinisch-prognostischer Faktoren für die Behandlung fortgeschrittener Ovarialkarzinome.

25 patients with stage III and IV ovarian carcinoma were treated with radical surgery and postoperative chemotherapy. Analysis of the disease-free intervals and the survival rates indicated significant differences related to the stage of the disease. Furthermore patients with minimal residual disease (tumor mass less than 2 cm in diameter) had a far better prognosis than patients with extensive residual disease (greater than 3 cm). No correlation could be demonstrated between histological grading, in vitro proliferation rates, hormone receptor status, type of postoperative chemotherapy and survival rates.

[5 years' experiences with adjuvant chemotherapy in primary breast cancer]. / 5jährige Erfahrungen mit adjuvanter Chemotherapie beim primären Mamma-karzinom.

In 515 patients with primary carcinoma of the breast T1a-3aN1a-bM0, the authors conducted simple mastectomy with radical lymphonodectomy of the axilla from 1976 onwards to the time of reporting. In 190 patients with affected lymph nodes, assisting chemotherapy was effected with a combination of three drugs, namely, trofosfamide, methotrexate and 5-fluoro-uracil for a period of 12 months postoperatively. Patients whose lymph nodes remained free were not subjected to follow-up treatment. For both groups of patients, the rates of relapses and survival times were established for an average follow-up time of 41 months (15-75). No significant differences in the rates of relapses and localisation were seen on comparing both groups (P = 0.27). In the patients with affected lymph nodes, local relapses were somewhat more frequent than with patients whose lymph nodes were not affected (11.1% vs. 9.8%); the same also applied to the occurrence of metastases distant from the primary tumour (12.1% vs. 7.4%). Significant differences in survival rates in patients with affected lymph nodes were seen only in the tumour stages T1/T2 (P = 0.001) and for the stages T2/T3 (P = 0.009). The menopausal status of the patients did not show any significant differences in respect of probability of survival for both groups (N-:P = 0.75; N+:P = 0.79).

In vitro growth promotion of human mammary carcinoma cells by steroid hormones, tamoxifen, and prolactin.

Individually different growth responses of 10 cell lines newly derived from metastasizing mammary carcinomas were determined by cell counts in experimental incubations with the steroid hormones 17 beta-estradiol, progesterone, testosterone, hydrocortisone (cortisol), the antiestrogenic compound tamoxifen, or prolactin. Of 7 cell lines derived from ductal carcinomas, 5 were stimulated by prolactin. The growth of 4 of 7 cell lines established from the tumors of postmenopausal or ovariectomized patients was enhanced by doses of testosterone, which are in the range of the physiologic serum level. The proliferation of 5 cell lines was promoted by hydrocortisone in the physiologic concentration of 100 nM, supporting the notion that concentrations of testosterone or hydrocortisone normally present in body fluids may facilitate the in vivo growth of breast cancer. The in vitro growth of cells derived from tumors after relapse under treatment with medroxyprogesterone acetate or tamoxifen was markedly enhanced by progesterone or tamoxifen (CAS: 10540-29-1) in concentrations corresponding to therapeutical serum levels and in accordance with in vivo resistance to the endocrine therapy applied before cell sampling. The results of this suggest the occurrence of positive endocrine selection mechanisms operating in vivo on human mammary tumor cell populations.

9. Steroid receptors. Correlation of estrogen and progesterone receptor status with ultrastructural differentiation in breast tumors.

The interrelationships of ultrastructural and biochemical parameters have been studied in a multivariate analysis of 139 cases of invasive breast carcinoma. There was no relationship between the histologic subclassification and distribution of estrogen and progesterone receptors. However, significant correlations could be found between receptor status and certain ultrastructural features of the tumor cells. A prevalence of well differentiated cancers had a significant correlation with a positive estrogen receptor status. Estrogen receptors were more frequently associated to tumors showing great complexity of cytoplasmic organization, high degrees of cell interconnections by desmosomes and membrane interdigitations, presence of intracytoplasmic ductules, specific secretory granules, and low grades of nuclear pleomorphy. In a series of 120 non-selected cases, receptor status was assessed by the fluorescent technique. Of the cases, 38.3% have proved to be ER+, 49.2% showed low binding capacity and 12.5% were negative. The correlation of receptor content with the histological type of breast cancer revealed some type-dependent connections. While only 36.9% of the solid tumors were receptor positive the proportion increased to 54.2% for the more differentiated glandular type of ductal carcinoma. 8 out of 13 (61.5%) infiltrating lobular carcinomas and 4 (4) colloid cancers were found to be receptor positive. The plotting test showed a good correlation of histochemical receptor status and histological grading. Although the type of "receptor", which is localized by the indirect fluorescent technique is still incompletely defined, there is no doubt, that the selective binding affinity reflects a specific capacity of the tumor cells depending on their degree of differentiation.

[Post-operative complications following Caesarean section. A comparative study of the years 1957-1958 and 1977-1978]. / Postoperative Komplikationen nach Sectio caesarea. Eine vergleichende Analyse der Jahre 1957/1958 und 1977/1978.

104 Caesarean sections of the Obstetric Department of the University in Hamburg-Eppendorf of the years 1957-1958 were compared with 399 Caesarean sections of the years 1977-1978 in a retrospective study. An attempt was made to correlate the post-operative complications with possible causes. There was a marked rise in wound infections, endometritis, post-operative pyrexia and a decrease of thromboembolic complications and retained lochia. Differences in the old and new years were in the management of labour, the operative technique and the post-operative treatment. In the Caesarean sections of 1977 to 1978 a clear cut correlation between wound infections uterine complications and pyrexia and the number of vaginal examination following rupture of the membranes the duration of rupture of the membranes and the length of labour was found. To reduce the post-operative complication rate at attempt should be made to reduce the number of vaginal examinations, to be stringent in the indications for rupture of the membranes and to avoid delay in inevitable Caesarean sections.

[Ancillary chemotherapy with trofosfamid, methotrexate and fluoro-uracil in cancer of the breast (author's transl)]. / Adjuvante Chemotherapie mit Trofosfamid, Methotrexat und Fluoro-uracil beim Mammakarzinom.

The results of adjuvant chemotherapy in the treatment of primary cancer of the breast is reported. During 44 months 401 patients were admitted to the prospective study. All patients with a cancer of the breast T1a-3a, N0-1b, M0 were operated by modification of the Patey procedure. N+ patients were treated for one year postoperatively with TMF chemotherapy (trofosfamid, methotrexate and Fluoro-uracil). Patients without lymph node metastases were not treated. After 44 months the recurrence rate in the TMF group was 16.2%, in the group without chemotherapy 9.8%. The recurrence rate in the treated group was 18.8% for post-menopausal patients and 13.8% in pre-menopausal patients. The number of distant metastases was higher than that of local recurrences. In the group without post-operative chemotherapy a higher number of recurrences occurred in the pre-menopausal patients (13.8%) than in the post-menopausal patients (7.5%). The proportion of local recurrences and distant metastases was the same in these patient groups. The experiences regarding the treatment plan and the side effects are the same as in comparable other studies of adjuvant chemotherapy. Several treatment plans are discussed which can lead to a reduction of the recurrence rate and to an improvement of the survival rates.

Estrogen receptor status and response to polychemotherapy in advanced breast cancer.

In a retrospective study, response to systemic polychemotherapy was analyzed in 72 female patients having advanced breast cancer and correlated with estrogen receptor (ER) status. Estrogen receptors were analyzed by agar-gel electrophoresis or uptake competition technique in tumor biopsy specimens derived from the primary tumor or from metastases. The borderline between positive and negative ER values was declared to be 20 fmol/mg tissue protein. Most of the patients have had an extramural review. We did not find statistically significant differences between the ER-positive (ER+), and ER-negative (ER-) groups in these characteristics: age; menopausal status; disease-free interval; dominant site of involvement. Chemotherapy regimens utilized in the two groups were comparable. According to criteria formulated by the European Organization on Research and Treatment of Cancer (EORTC), there is no evidence that response to chemotherapy is correlated with the presence or absence of estrogen receptor. Thirteen of 31 ER+ patients responded objectively to chemotherapy (42%) and 17 or 41 ER- patients gained such remission (41%). Given the retrospective nature of the data, this result should be interpreted cautiously. More clinical studies are warranted to determine whether response to cytotoxic agents is affected by ER status.

The problem of nonresponding estrogen receptor-positive patients with advanced breast cancer.

Patients with advanced breast cancer and low or poor concentration of estrogen receptors in tumor biopsies have little chance of responding to endocrine therapy. This problem was seen in a group of nonresponding estrogen receptor-positive (ER+) patients. Some comments on possible explanations for this phenomenon are made and suggestions to overcome it are given.

[The clinical value of hormone receptors in the treatment of breast neoplasms]. / Die klinische Bedeutung von Hormonrezeptoren bei der Behandlung des Mammakarzinoms.

PIP: Endocrine hormone treatment has been found to be effective in treating metastatic breast cancer in 20-40% of the cases. The effectiveness of this treatment can be predicted to a certain extent by determining whether the hormone receptors in the tumor tissue react positively or negatively when incubated with highly active hormones, e.g. H3-17 beta-estradiol. Estrogen receptors are found in 60-70% of primary tumors and 40-50% of tissue samples from metastatized tumors. Estrogen receptors are more frequently found in post-menopausal women than in women who are still menstruating. Progesterone receptors have been found in 20-40% of all investigations undertaken, androgen receptors in 20-30%, and corticosteroid receptors in 20-50%. A remission rate of 56% has been achieved after endocrine therapy of those with positive estrogen receptor tests, compared to 10% among those with negative tests. The correlation between the receptor test results and (the success of) endocrine therapy is not very high; this could be a factor determined by the cellular constitution of a tumor. The remission rate is 75% among patients with positive receptor tests for both estrogen and progesterone. Faulty lab techniques could be responsible for low correlation. Determination of the receptor activity of both the primary tumor and its metasases, or immunological or immunohistological determination of receptor activity may improve the usefulness of the test in determining tumor reaction to endocrine hormone treatment.^ieng

[The clinical significance of hormone receptors in the treatment of breast cancer]. / Die klinische Bedeutung von Hormonrezeptoren bei der Behandlung des Mammakarzinoms.

The assay of steroid receptors in tumor tissue has been shown to be a useful tool to evaluate the response of disseminated breast cancer to endocrine therapy. Principle and problems of this assay are outlined. An objective response of estrogen-receptor positive tumors to endocrine treatment can be achieved in about 60%. The rate of remissions in the receptor-negative group is below 10%. Possible explanations for false-positive or false-negative receptor assays are discussed. Additionally some possibilities for increasing the accuracy of the method are detailed.