[Surgical therapy of ovarian cancer].
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Biomedical subjects
Publications and source records attributed to A Pfleiderer.
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As previously reported, ovarian epithelial carcinomas may respond to endocrine therapy. We examined the direct effect of progesterone, medroxyprogesteroneacetate, gestoneron, 17-beta-estradiol, tamoxifen, 4-OH-tamoxifen, or N-desmethyltamoxifen on the proliferative capacity of ovarian carcinoma cells by means of the colony assay described by Hamburger and Salmon. The growth rate of 25 tested tumors (ascitic fluid, primary tumor, metastases) was 68%. The plating efficiency was 0.078%. Beside the drug testing estrogen and progesterone receptor levels were determined. The inhibition of colony survival was slightest with 17-beta-estradiol, more pronounced with medroxyprogesteroneacetate, gestoneron, N-desmethyltamoxifen, and progesterone, and greatest with 4-OH-tamoxifen and tamoxifen. Significant and dose-dependent inhibition of greater than 70% was observed with tamoxifen and 4-OH-tamoxifen in 80% of the tested tumors. There was no significant correlation between the in vitro responsiveness and the level of hormonal act not only via an estrogen receptor but also via an antiestrogen-binding site.
The human tumor colony forming assay was used to evaluate the response of ovarian carcinoma cells from primary tumors, ascitic fluids and metastasis to hormonal treatment. In 12/35 patients a sufficient colony formation (greater than 30 colonies/dish) was obtained in order to perform a simultaneous drug testing. The plating efficiency of the metastatic samples (0.12%) was significantly higher (P less than 0.053) than those from the primary tumor (0.076%) or those that were derived from the ascitic fluid (0.082%). Colonies from the metastatic tissues could be evaluated 2-4 days earlier than those from primary tumors. These discrepancies may be due to a heterogeneity in the clonable tumor cell compartment of primary tumor and metastasis. The antiproliferative properties of the antiestrogen tamoxifen and the progestin gestoneron were studied. In 9/12 cases a significant, dose-dependent reduction of colony formation (greater than 70-90% of the controls) was observed after continuous exposure to 1 mumole tamoxifen. No correlation between the dose response and the content of steroid receptors was found. Even estrogen receptor negative tumor samples showed a maximal antiproliferative effect of tamoxifen.
The evaluation of 259 peritoneal cytologic specimens obtained intraoperatively in cases of malignant ovarian tumor revealed positive findings in 62.5%; findings were doubtful in 2.3% and unusable in 2.7%. In the cases with clinically apparent peritoneal carcinomatosis, (n = 175), cytologic tests were positive in 75%. Taking tumor histology into account the high proportion of positive findings among the non-classifiable tumors (11 out of 13) was striking. For this reason, in a second investigation, 144 peritoneal cytologic specimens taken exclusively from cases of serous carcinomas were studied with regard to their degree of differentiation, the time of removal, and tumor spread. The peritoneal cytology was positive in 33% of the cases without peritoneal carcinomatosis at the first operation and in 36% of the cases with only histologically detectable tumor remnants at the time of the second-look operation. With one exception, peritoneal cytology was also negative in 26 second-look cases without clinically or histologically detected tumors. The incidence of positive peritoneal cytology findings was significantly higher in serous tumors with low-grade differentiation.
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Non-puerperal mastitis was diagnosed in 79 patients (aged 12-77 years) over the years 1974-1984. Malignant neoplasm was not present. Bacterial infection in the region of the areola was the most frequent finding (40%), followed by abacterial inflammation without involvement of the nipples (29%). The other cases, bacterial or nonbacterial, occurred at different sites. The histological picture or clinical features of an increased secretory activity of the mammary gland (galactorrhoea, mastodynia) in addition to the mastitis was noted in 54 women. Causative organisms were proven in 53% of cases: Staph. aureus (41%) and coagulase-negative staphylococcus (41%), or anaerobic organisms (11%). Physical measures, antibiotics and bromocriptine were used as treatment. At the onset of treatment abscesses were already present or developed in 34 instances. In 28 cases one to six recurrences set in after the end of the treatment period. In 22 patients treated with bromocriptine prophylactically there were only two recurrences. In the majority of patients an increased alveolar secretion was important in the pathogenesis of the bacterial or abacterial inflammation. Prolactin-lowering treatment seems reasonable by itself in cases of abacterial mastitis, or in combination with antibiotics in bacterial mastitis. Recurrences can be prevented by long-term lowering of the peripheral prolactin level.
Human ovarian cancer cells from ten patients were cultured in the agar double layer assay as described by Hamburger and Salmon and in a methylcellulose monolayer system. The assays were compared under the same experimental conditions. The rate of positives (defined as greater than 30 colonies/dish) was 75% in the methylcellulose assay and 69% in the agar double layer. Plating efficiency ranged in the methylcellulose assay between 0.021% and 0.089% and in the agar double layer from 0.015% to 0.094%. Cytological and cytochemical staining of cells obtained from colonies in both test systems and of the tumour cells prior to plating revealed the same morphology. The methylcellulose monolayer system requires less additives than necessary in the agar double layer system. Furthermore, it is easier to handle with respect to the plating procedure and less time consuming. In addition, the effect of the anti-oestrogen tamoxifen on colony formation was tested. The dose response curves for colony formation with tamoxifen proved to be identical in both systems. At a concentration of 10(-6) M an inhibition of colony formation of more than 70% of controls was observed in the agar and in the methylcellulose system.
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The importance of a second-look operation (SLO) in 121 patients with ovarian carcinoma stages III and IV from 1979 to 1983 is forthwith discussed. This operation was carried out in 58% of the patients. If no tumor was suspected after chemotherapy (n = 33), this only applied in 19 cases after a SLO. Of the patients in partial remission the preoperative diagnosis was correct in 14 of 21 cases and in no change 4 of 9 cases. Clinically the progress was always diagnosed reliably. Additional removal of residual tumors was successful in 7 of 49 cases (14%). This is only possible in small quantities of residual tumor. An improvement in the prognosis did not occur. Predictions on the right time to carry out a SLO and the purpose of a secondary tumor resection cannot be made.
In a cooperative study specimens of 37 patients with stage III and IV ovarian carcinomas who had been treated with chemotherapy were investigated utilizing flow cytometry and an in vitro short-term test for predicting resistance. Patients with aneuploid tumors had significantly shorter survival rates than did those with diploid tumors. Patients whose tumors showed a low G0/G1 cell proportion or a high proliferation pool (S- and G2/M cell-proportion) seemed to die earlier. There was also a tendency for patients with in vitro resistant tumors to die earlier under chemotherapy than those with sensitive tumors.
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A modern and optimal follow-up treatment of patients with uterine cancer requires a detailed knowledge of this disease and its sequelae. Incidence and localisation of cervical and endometrial cancers as well as kind and incidence of therapeutical side effects are demonstrated in the cases of the Gynecological University Hospital of Freiburg, GFR. A study of the psychosexual situation 2--4 years after therapy of uterine cancer is reported. Actual state of social assurances for cancer patients in the German Federal Republic is pointed out. The dates allow to draw conclusions for the follow-up of individual cases.
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The absorption and transport pathways of Conjunctisan A were determined, and its mode of action clarified, by means of radioactive labeling. A dose of 0.5 ml of this drug, labeled with I131, was applied to the conjunctival sacs of rats and rabbits. After six hours there was highly significant enrichment in the ocular tissues. The highest degree of enrichment was found in the uvea, i.e., the ciliary body, choroid and retina. However, there was also moderate enrichment in the lens and the vitreous. It was proved immunologically that the radioactivity was identical with the original Conjunctisan A molecule. In particular, it as demonstrated that the enriched Conjunctisan A in the aqueous humor precipitates with the specific antibody.
The behaviour of 34 carcinomas of the cervix and 30 ovarian carcinomas under the influence of cytostatic agents was investigated in vitro by the method of Volm et al. The ovarian carcinomas showed a significantly higher incorporation rate of nucleotide precursors in the single cell suspensions. The incorporation rate in "chemosensitive" carcinomas was higher than in "chemoresistent" carcinomas independent of the type of the carcinomas. Carcinomas with a high decrease in incorporation rates of nucleotide precursors under the influence of cytostatic drugs were called chemosensitive. A cyclophosphamide-sensitivity in vitro was found in 9% of the carcinomas of the cervix and in 34% of the ovarian carcinomas. An adriamycin-sensitivity in vitro could be shown in 17% of the carcinomas of the cervix and in 46% of the ovarian carcinomas. These findings agree well with the experiences of cytostatic therapy of these carcinomas.
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