Adjuvant tamoxifen in postmenopausal patients with breast cancer and negative axillary lymph nodes.
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Biomedical subjects
Publications and source records attributed to H Salzer.
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The present retrospective study attempts to evaluate the significance of factors such as age, histological type, histological grading, tumour size, lymph node metastases and tumour infiltration of the corpus uteri. Between 1975 and 1988, 312 patients were operated at our department or referred to postoperative radiotherapy. They fulfilled the inclusion criteria: histopathological stage Ib and radical hysterectomy with pelvic lymphadenectomy. The multivariate analysis confirmed, that the factors histological grading (G3 vs G1 + G2: relative risk (RR) = 2.66; 95% confidence interval (CI) = 1.36-5.18), tumour size (tumour infiltration of the cervix greater than 2/3 vs less than 2/3: RR = 2.36; 95% CI = 1.07-5.17), and pelvic lymph node metastases (positive vs negative: RR = 5.36; 95% CI = 2.70-10.65) are of significant importance for the survival. The results show, that patients with a cervical carcinoma in FIGO stage IB, with an infiltration of more than two thirds of the cervix with a more or less differentiation and with or without positive lymph node status, should be classified as high risk patients. In these unfavourable situations, a prospective randomised study should clarify the success rate of adjuvant therapy.
The evolution in the management of ovarian cancer at the First Department of Obstetrics and Gynecology of Vienna University is reviewed. The improvement in radical surgery and a more rational application of adjuvant treatment modalities produced a relative improvement in 5 year survival in the last period under review.
In routine analysis for immunoglobulin light chains in pediatric diagnostics, the age-related reference intervals for serum kappa (kappa) and lambda (lambda) light chains were evaluated in 1543 healthy subjects (newborns to age 16 years, including 168 premature infants). Light-chain analysis was performed by rate nephelometry. IgG, IgA, and IgM were measured simultaneously, and heavy- and light-chain differences were calculated for control purposes. Results for IgG, IgA, and IgM generally agreed with reference intervals reported in the literature. kappa showed age-related changes comparable with changes in IgG concentrations, whereas lambda showed moderate fluctuations. The kappa/lambda ratio showed an almost linear increase with age, starting with 0.97 at four months and reaching the highest value of 2.21 at 15 years (mean values). Preterm infants presented with markedly low serum concentrations of IgG and corresponding light chains but with adult-type kappa/lambda ratios because of the maternal-origin IgG.
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Between December 1983 and December 1988 we examined the postoperative tumor marker development and correlated this to the clinical course of the disease in 56 patients suffering from primary epithelial ovarian carcinoma of International Federation of Gynecology and Obstetrics stages I-III and with a preoperative CA-125 serum level less than or equal to 65 U/ml. In 54% of all cases there was a reduction of more than 50% of the CA-125 serum level within the first 3 months after surgery. Nine out of thirteen patients with progressive disease (69%) showed an increasing CA-125 serum level with a median lead time of 6 months (0-11 months) prior to clinical diagnosis. These preliminary results indicate that the monitoring of cancer patients with CA-125 tumor marker seems to be a useful method of early diagnosis of progressive disease even in patients with preoperative serum levels lower than 65 U/ml.
Aim of the study was to find out the influence of iron medication of pregnant women on the iron levels of their newborn. In a prospective randomised study the iron-substituted group (n = 57) was treated with 2 x 1 Aktiferrin comp. Kps. (Merckle) during pregnancy, starting from the 22nd week. The control group (n = 46) had no medication during pregnancy. The substituted group had statistically significantly higher serum ferritin levels in the 30th week of pregnancy (p less than 0.048), higher levels measured in the cord blood at birth (p less than 0.001), and also the newborn of this group had statistically significant higher serum ferritin levels than the newborn of the control group (p less than 0.001). Our conclusion is that prepartal iron medication leads to increased iron stores in the newborn.
145 women (22.2%) out of 652 patients with primary breast cancer, who were operated on between January 1980 and September 1988, developed tumour relapse until May 1990. The aim of our retrospective analysis in these 145 patients with local and/or distant tumour relapse was to evaluate the prognostic importance for further survival of the following factors: menopausal status, stage of disease, number of involved axillary lymph nodes, tumour grading, ER and PgR content, postoperative irradiation, adjuvant treatment, localisation of tumor relapse and relapse-free interval. Multivariate stepwise regression analysis of all these factors identified the number of positive axillary lymph nodes (0-3 versus 4+) with a relative risk (RR) of 2.49 and localisation of tumour relapse (local versus visceral metastasis RR = 2.08 and local versus bone metastases RR = 2.08) as the only two significant prognostic factors for further survival. Therefore, these two factors should be stratification criterias for prospectively randomized phase III studies in patients with tumour relapse after primary breast cancer.
A retrospective analysis was performed to investigate the prognostic value of growth in a human tumor clonogenic assay system for 84 ovarian cancer patients. A significant difference in survival probability (determined by the method of Kaplan-Meier) was found by univariate analysis between patients with ovarian carcinoma whose tumors manifested clonogenic growth (defined as growth of greater than or equal to five colonies per plate) and patients whose tumors did not grow. Clonogenic growth in vitro was associated with worse prognosis (P = .007, log-rank test). A number of generally accepted prognostic factors, International Federation of Gynecology and Obstetrics (FIGO) stage (P = .003), residual tumor mass (P less than .001), and grade (P = .011), were also of prognostic importance in our patient population. Multivariate analysis, based on the Cox regression model, identified clonogenic growth as a significant independent prognostic parameter in ovarian carcinoma (P = .031), in addition to the conventional risk factors. Estimation of survival of individual patients was best accomplished by combining the factors of residual tumor mass (P less than .05), age (P less than .01), and clonogenic growth (P less than .05) (in sequence of decreasing potential of risk).
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The present retrospective study attempts to evaluate the significance of adjuvant radiotherapy as a prognostic factor for stage Ib cervical carcinoma without lymph node metastases in addition to factors such as age, histological type, histological grading and tumor size. Between 1975 and 1987 224 patients were operated at our department or referred to postoperative radiotherapy and fulfilled the inclusion criteria: histopathological stage Ib, radical hysterectomy with pelvic lymphadenectomy and negative pelvic lymph nodes. The multivariate analysis confirmed that tumor size (tumor infiltration of the cervix greater than 2/3 vs less than 2/3: RR = 4.48) and histological grading (G3 vs G1 + G2: RR = 3.12) are significant prognostic parameters for survival. Postoperative adjuvant irradiation is a marginal significant factor for survival in stage Ib cervical carcinoma and negative nodes (RR = 3.22; p = 0.057). For women with negative nodes but high-risk prognostic factors in the cervix, a prospective randomized trial proving the value of postoperative irradiation would be of therapeutic interest.
The value of surgery in early ovarian cancer was assessed in a retrospective analysis of prognostic factors in all 222 patients with primary stage I epithelial ovarian carcinoma treated in this department between 1975 and 1987. Only cellular differentiation grade (p less than 0.03) and surgical procedure - total abdominal hysterectomy, bilateral salpingo-oophorectomy +/- omentectomy vs. unilateral salpingo-oophorectomy - (p less than 0.02) were of significant influence on estimated survival (Cox model). All other factors (age, FIGO stage, integrity of the capsule, uni-vs. bilaterality, histology) were of no prognostic importance. Unilateral salpingo-oophorectomy without any additional staging reduces the 5-year survival probability (62% vs. 84%). Future prospective studies on adjuvant therapy must be based on exact staging during surgical management before randomisation. Determination of cellular differentiation is also essential.
40 patients with advanced epithelial ovarian carcinoma were investigated to evaluate the influence of further cytoreduction during second-look surgery on survival after termination of first-line polychemotherapy containing cisplatinum. Radical tumorectomy with no macroscopic residual tumor mass was achieved in 27.5% of cases; in 52.5% the residual tumour mass was less than 2 cm and in 20% it was more than 2 cm in diameter after cytoreductive second-look surgery. Median survival time after second-look within these three groups of patients was 15.2 months, 16.9 months and 15.3 months, respectively (Mantel test, p = 0.74). In contrast to the situation at the diagnostic operation, further cytoreduction during second-look surgery has no positive influence on survival. We therefore abandoned this operation in clinically tumour-positive patients.
Although glucocorticoids have been universally implemented to stimulate fetal lung maturity, their effectiveness and side effects are still widely contested. In search of alternative drugs a double-blind study was conducted between June 1981 and June 1984 comparing betamethasone, a conventional corticoid, and ambroxol, a bromhexine metabolite for efficacy and tolerance in prenatal prevention of the respiratory distress syndrome (RDS) in premature infants and full-term neonates. The therapeutic efficacies of betamethasone and ambroxol for this indication proved to be comparable. Since the possible risks of corticoid therapy in abnormal pregnancies are repeatedly discussed in the literature and in daily clinical practice. 137 patients with EPH gestosis, placental insufficiency, diabetes mellitus, and premature rupture of the membranes were selected from the original group of 308 patients. Only minor side effects (e.g. nausea) were present in a few of the 137 cases undergoing treatment with the 2 test substances. No side effects were observed in the neonates. The incidence of fetal RDS was comparable in both groups (2.9% with ambroxol, 2.2% with betamethasone). Transient and mild RDS cases were slightly more frequent in the ambroxol group than in the betamethasone group. To date, contraindications to ambroxol treatment in abnormal pregnancies are unknown and since generally the rate of potential side effects is considered to be lower in comparison with corticoid treatment, the use of ambroxol especially in abnormal pregnancies corresponding indication can be recommended.
In a retrospective analysis prognostic factors were studied in 204 patients with primary Stage I epithelial ovarian carcinoma (borderline tumors were excluded) treated between 1975 and 1987. Only histologic grade (P = 0.01) and kind of surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy +/- omentectomy versus unilateral salpingo-oophorectomy, P = 0.02) were found to have a significant influence on survival prognosis (Cox model). All other factors (age, the International Federation of Gynecology and Obstetrics [FIGO] stage, integrity of the capsule, unilaterality versus bilaterality, and histology) were of no prognostic importance. Unilateral salpingo-oophorectomy without any additional staging reduces five-year survival probability (62% versus 84%). Therefore this kind of operation should be abandoned. Furthermore, histologic grade should be a stratification criterion in studies, which will be necessary for proving the value of adjuvant therapy in Stage I epithelial ovarian carcinoma.
Clonogenic growth (defined as the formation of greater than or equal to 5 colonies per 5 x 10(5) viable nucleated cells per plate) of ovarian cancer specimens assessed in our clonogenic assay system was significantly associated with the proportion of tumor cells in the suspensions plated (N = 87; P = 0.0006), although there was no quantitative relationship with the corresponding plating efficiencies. An inverse correlation was observed between monocytes/macrophages/mesothelial cells (M) proportion and clonogenic growth (P = 0.013). These associations were most evident when only effusions were considered. Univariate analyses identified tumor cell content, M proportion and, to a lesser degree, granulocyte content as the only factors out of 12 examined to be correlated with colony formation. Multivariate analysis using a logistic regression model identified the proportion of tumor cells as the only significant factor predicting clonogenic growth in vitro (P = 0.0006). The overall accuracy of prediction for growth or non-growth was 63.2%.
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On the basis of the results of earlier studies, 30 departments of gynecology have been cooperating nationwide in Austria since 1980 to promote the use of adjuvant chemotherapy after surgery for cure of ovarian carcinoma in early stages and the role of lymph node dissection and of second-look operation. Results recorded in more than 160 patients treated with adjuvant chemotherapy after so-called radical surgery performed in disease stages I and II demonstrate that only highly differentiated tumours in stage Ia can be cured by surgery only with no further adjuvant treatment. This underlines the necessity for staging. More than 200 patients with TNM stages III and IV were randomized after debulking surgery to receive treatment with different kinds of drug combinations to compare the therapeutic efficacy of a sequential alternating drug regimen consisting of Adriamycin-cisplatin + vincristine-cyclophosphamide + high-dose methotrexate with that of the combination of Adriamycin-cyclophosphamide and that of Adriamycin-cisplatin. High-dosed ifosfamide was also used in pilot studies.