[Intravaginal brachytherapy in surgically treated uterine cancer]. / Intravaginale Brachytherapie beim operierten Korpuskarzinom.

We analyzed retrospectively the clinical outcome of 108 patients with endometrial carcinoma operated at the Department of Obstetrics and Gynecology of Düsseldorf University regarding the effect of additional intravaginal brachytherapy. In 67 patients, we only performed an intraoperative rinsing of the vagina with alcohol and sutured the cervical canal to prevent vaginal recurrences. 41 patients received additional intravaginal brachytherapy. We observed only two vaginal recurrences in the 108 patients. There was no major difference in survival for patients with versus without additional intravaginal brachytherapy. We reviewed published studies critically regarding the efficacy and complications of intravaginal brachytherapy in operated endometrial cancer. These studies indicate that additional intravaginal brachytherapy can lower the rate of vaginal recurrences and that patients with dedifferentiated tumors, deep myometrial invasion and higher FIGO-stages might benefit most of this treatment modality.

[Autologous and heterologous blood transfusion in obstetrics]. / Eigen- und Fremdbluttransfusionen in der Geburtshilfe.

We retrospectively analyzed the frequency and details of blood transfusions in a group of 12,578 obstetrical patients. We found 250 patients who received red blood cell transfusions resulting in a transfusion rate of 2 in 100. In most of these cases, there were no risk factors placing patients at high risk for blood transfusions. The administration of one or two units of blood was adequate in 76% and of up to three units adequate in 87% of cases. Our results do not support a commercial blood bank's recent claim of frequent transfusions in obstetrical patients. We feel that the routine storage of blood for autologous transfusions is not warranted in obstetrical patients.

[Experiences with after care of patients with breast cancer]. / Erfahrungen in der Nach-sorge von Patientinnen mit Mammakarzinom.

We retrospectively analyzed methods of follow-up and subsequent clinical outcome in 399 breast cancer patients treated with curative intent. Radioisotope liver scans, liver sonograms and laboratory investigations were of little value in detecting metastases. Mammography detected 2 of 6 contralateral breast cancers in an asymptomatic stage. Of 92 metastatic diseases, 24 were disclosed by a total of 871 radioisotope bone scans, and 17 were disclosed by a total of 2409 chest x-rays. The detection of distant metastases in an asymptomatic stage by diagnostic procedures vs detection by symptoms was not correlated with a survival benefit. The survival times for the two groups were 6.4 years vs 6.7 years (p = 0.7) after initiation of primary therapy, and 20.8 vs 20.4 months (p = 0.9) after the diagnosis of metastatic disease. Our study does not lend support to the hypothesis that the detection of metastatic disease in an asymptomatic stage or regular follow-up visits are associated with a survival benefit. We conclude that clinical history, physical examination, and mammography are the most important procedures in the follow-up of breast cancer patients.

The value of preoperative chest X-rays in gynecological patients.

We assessed the value of preoperative chest x-rays in gynecological patients. Abnormalities were noted in the chest x-rays of 10% of 1175 patients with genital or breast disorders. When the chest x-ray was abnormal, 48% of patients had no clinical features of intrathoracic disease. Abnormal chest x-ray results did not seem to have a major influence on the decision to operate or on the type of anesthesia used. In our series, probably only one patient would have received inappropriate treatment in the absence of a chest x-ray. We conclude that preoperative chest x-rays are of value in ruling out metastases in patients with a suspected neoplasm, but have little value in other circumstances.

Barium enema in the diagnostic work-up of gynecologic patients.

We evaluated the role of the barium enema in the diagnostic work-up of 120 gynecologic patients. Major abnormalities were detected in 10% of patients. We conclude that patients presenting with pelvic tumors or suspected gynecologic malignancies should have a pre-therapeutic barium enema in order to define the extent of the disease and to rule out colon cancer.

[Recurrent mastitis with an unusual etiology]. / Rezidivierende Mastitis mit ungewöhnlicher Atiologie.

We present the diagnostic and therapeutic problems in a patient presenting with recurrent, refractory necrotising mastitis that was caused by artifacts.

Role of culture conditions and exposure duration in determining sensitivity of human bone marrow progenitor cells to methotrexate.

The effect of drug concentration, exposure duration, and culture conditions on the cytotoxic activity of methotrexate (MTX) on normal granulocyte-macrophage colony-forming units in culture (GM-CFUC) was studied using a bilayer soft agar system with nucleoside-free medium. The degree of inhibition of colony formation depended on the type of serum supplementation. A 1 h or 2 h pulse treatment with 2 X 10(-4) M (100 micrograms/ml) MTX failed to kill GM-CFUC, when the cells were subsequently plated in a system containing 15% undialyzed fetal bovine serum (FBS). For continuous exposure the observed LD50 of MTX in the agar system was higher than 10(-4) M for 15% undialyzed FBS, 10(-5) M for 15% dialyzed FBS plus 0.25% undialyzed FBS, 10(-6) M for 15% dialyzed FBS, and 10(-8) M for 15% undialyzed horse serum. The difference for dialyzed FBS versus horse serum can be explained by differences in nucleoside concentrations. The difference for dialyzed FBS versus horse serum may be secondary to an enhancer of MTX in horse serum. For studying MTX sensitivity of human tumor cells in vitro, we suggest testing conditions that lie within the dose survival curve of GM-CFUC.

The human tumor stem cell assay revisited.

The human tumor stem cell assay (HTSCA) is a bilayer soft agar system for growing fresh human tumor specimens in vitro to determine drug sensitivity and improve our understanding of tumor biology. Recent clinical correlations of 60% accuracy for predicting a positive clinical response and a 90% accuracy for predicting a lack of response to therapeutic agents suggest promising clinical usefulness. However, the clinician should be aware of the assay's inherent pitfalls, such as heterogeneity of the tumor specimen, inability to obtain pure single-cell suspensions, low cloning efficiency, unusual drug dose-dependent survival curves, uncertain validity of in vitro pharmacology, non-standardized criteria for in vitro sensitivity, and the variability of in vitro results. A brief summary of the concepts, potential, and limitations of this assay are discussed.

Survival of human bone marrow cells after in vitro treatment with 12 anticancer drugs and implications for tumor drug sensitivity assays.

We investigated the responsiveness of human normal granulocyte-macrophage colony-forming units in culture (GM-CFUC) continuously exposed in vitro to 1 of 12 anticancer drugs. All drugs except bleomycin showed a simple negative exponential dose-survival curve. The in vitro toxicity of drugs in GM-CFUC did not always correlate with the relative myelosuppressive potency observed in vivo. In addition, tumor specimens from 38 patients mainly with ovarian cancer were cultured in a human tumor colony-forming assay and continuously exposed to drugs at low, intermediate, and high concentrations capable of killing 40%, 78%, and 99% of GM-CFUC, respectively. The most active drugs were cis-platinum, velban, 5-fluorouracil, and 5-fluoro-ara-AMP. Dose-survival curves of bone marrow progenitor cells may serve as an in vitro reference system for selecting appropriate drug concentrations of myelosuppressive drugs in drug-sensitivity assays of human tumors.

Experiences with the human tumor colony-forming assay in gynecologic malignancies.

Tumor samples from 74 patients with gynecologic malignancies including breast cancer were processed in a soft agar colony-forming assay. None of the samples resulted in a pure single cell suspension. Of the 10 samples meeting our criteria of evaluability for chemosensitivity testing, only 5 samples showed in vitro sensitivity to any drug. Of the 3 evaluable correlations between in vitro and in vivo results, 2 were correct. Due to the low rate of evaluable samples the assay has only limited value in the assignment of chemotherapeutic drugs for patients treated at our institution.

Intolerance to cisplatin--a case report.

A patient who had a systemic reaction to cisplatin chemotherapy had a reaction to subsequent i.c. and i.v. test doses. Notwithstanding she had a more severe systemic reaction during a further course of cisplatin chemotherapy.

Dose-survival curves of cis-platinum, melphalan, and velban in human granulocyte/macrophage progenitor cells.

To optimize the in vitro concentrations of anticancer agents with clinical dose-limiting myelosuppression in the human tumor stem cell assay, we established dose-survival curves for cis-platinum, melphalan, and velban in normal human granulocyte/macrophage colony-forming units (CFU-gm) in a bilayer agar system. The LD50 (drug concentration capable of killing 50% of CFU-gm) of cis-platinum, melphalan, and velban for one-hour exposure was (a) greater than 10 micrograms/ml, (b) 0.9 microgram/ml, and 1.2 micrograms/ml, respectively. The respective values for continuous exposure were 0.3 microgram/ml, 0.12 microgram/ml, and 0.001 microgram/ml. The use of dose ranges based on bone marrow tolerance may influence the clinical value of in vitro tumor sensitivity studies of drugs with hematologic toxicity.

Responses of human bone marrow progenitor cells to fluoro-ara-AMP, homoharringtonine, and elliptinium.

The cytotoxicity of the investigational anticancer drugs fluoro-ara-AMP, homoharringtonine, and elliptinium on normal human granulocyte-macrophage colony-forming units in culture (GM-CFU) was investigated using a bilayer soft agar system. For each drug, the dose-dependent survival curve on a semilogarithmic plot formed a straight line. The D0 were: 0.51 microgram/ml (fluoro-ara-AMP), 0.004 microgram/ml (homoharringtonine) and 0.026 microgram/ml (elliptinium). The in vitro toxicity of drugs on bone marrow progenitor cells did not correlate with the relative myelosuppressive potency observed in vivo.