Heinrich Salzer

Prognostic value of the rupture of the capsule in stage I epithelial ovarian carcinoma

The prognostic influence of the integrity or the rupture of the capsule was examined in 60 patients with stage I epithelial ovarian carcinoma. After an average follow-up of 75 months (range 30-120 months) the probability of 5-year survival was 76% in both groups. Therefore, we conclude that rupture of the tumor during surgery has no influence on survival rates. Consequently, these patients should not be considered as belonging to the subgroup stage IC ovarian carcinoma, as suggested by the FIGO committee.

Pregnancy-related changes of carnitine and acylcarnitine concentrations of plasma and erythrocytes

Total-, free-, and acylcarnitine concentrations were determined in whole blood, plasma, and red blood cells of 88 women during pregnancy. Already in the 12th week of gestation the mean whole blood carnitine level was significantly (p < 0.01) lower than those of the controls. From the 12th gestational week up to parturition there was a further significant (p < 0.01) decrease. This reduction of total carnitine in whole bloods was mainly caused by a significant (p < 0.01) decrease of free carnitine levels, since no marked changes of short chain acylcarnitine values were found throughout pregnancy. The contribution of red blood cell L-carnitine to whole blood carnitine increased significantly (p < 0.05) to 61% at delivery versus 39% (controls). In umbilical cord blood free and total carnitine levels were significantly (p < 0.05) higher than the corresponding maternal levels. The contribution of red blood cell L-carnitine to whole blood carnitine was higher in cord blood than in maternal blood. The results of the present study demonstrate that during pregnancy whole blood and plasma carnitine levels decrease to those levels found in patients with carnitine deficiency. Also the percentage of acylcarnitine on total carnitine, found in the present study, is characteristic for a secondary carnitine deficiency. Thus L-carnitine substitution in pregnant women, especially in risk pregnancies, may be advantageous.

Oestrogen and progesterone receptor content as a prognostic factor in advanced epithelial ovarian carcinoma

Summary. Levels of oestrogen receptor (ER) and progesterone receptor (PgR) in ovarian cancer tissue were examined with regard to their prognostic importance for survival in 179 patients with primary epithelial ovarian cancer stage III or IV in relation to: FIGO‐stage, histological type, histological grade, age, ascites, and postoperative residual tumour. Hormone receptor content was determined with the DCC‐method, receptor values higher than 9 fmol/mg protein were considered positive. Response to postoperative chemotherapy was significantly correlated with PgR content (80% responders in the group with PgR positive tumours and only 61% responders in the group with PgR negative tumours). A Cox proportional hazards regression model identified histological grade, residual tumour, age and PgR content as independent prognostic factors for survival in advanced epithelial ovarian carcinoma. PgR content had particularly significant prognostic relevance for patients with postoperative residual tumour mass ≤2 cm in diameter. Within this group of patients, those who are PgR positive have a 2‐years survival probability of 83% compared with only 51% in the Pg R‐negative group.

HER-2 and INT-2 amplification estimated by quantitative PCR in paraffin-embedded ovarian cancer tissue samples

Competitive polymerase chain reaction (PCR) systems were developed for rapid and quantitative estimation of HER-2 (c-erbB-2) and INT-2 oncogene amplification in paraffin-embedded ovarian cancer tissue samples. The beta-globin gene was used as reference and DNA from paraffin-embedded placenta tissue as single copy control. Reliability of the PCR method could be demonstrated by comparing dot blot data with PCR data of identical tumour samples. The PCR method was used to determine HER-2 and INT-2 copy numbers in 196 ovarian cancer samples. HER-2 and INT-2 were found to be amplified in 40 and 19%, respectively. In 8% HER-2 copy numbers were greater than five, but no high INT-2 copies were noted. Kaplan-Meier estimates did not reveal significant association with overall survival. Indirect correlation between HER-2 and INT-2 amplification was observed. The present PCR system is a valuable method for prospective and retrospective studies.

Clonogenic growth in vitro: an independent biologic prognostic factor in ovarian carcinoma.

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).

Ifosfamide/Mesna as Salvage Therapy in Platinum Pretreated Ovarian Cancer Patients—Long-Term Results of a Phase II Study

Purpose: Salvage chemotherapy in advanced ovarian cancer is not yet standardized. Patients: Twenty-one consecutive patients progressing on or relapsing after previous platinum-containing treatment were eligible for treatment with ifosfamide 5 g/m2 infused over a 24-hour period every 3 weeks in a Phase II trial. After an initial bolus of 1 g/m2 of mesna, mesna was applied at a dosage of 5 g/m2 concomitantly with ifosfamide followed by additional dosages of 200 mg 3 times at 4-hour intervals after termination of the ifosfamide infusion. Results: The rate of objective responses was 19 percent, with a 95%CI [5.45–41.91 percent]. One patient achieved a pathologic complete remission (pCR) and 3 patients a clinical partial remission (PR). Median time-to-progression was 3 months. One patient was a long-term survivor. Main toxicities according to NCI-CTC included Grade 4 neurotoxicity in one patient, Grade 3 gastrointestinal toxicity in 5 patients, Grade 3 infection in one patient, and Grade 3 and 4 leucopenia in 6 and 2 patients, respectively. Conclusions: Monotherapy with ifosfamide represents an active regimen for salvage chemotherapy in advanced ovarian cancer patients progressing on or relapsing after previous platinum-pretreatment, even yielding a long-term surivor.

Oral contraceptives that contain ethinyl estradiol (0.035 mg) and cyproterone acetate (2 mg) inhibit leukocyte transmigration through endothelial cell monolayers

OBJECTIVE To investigate the influence of ethinyl estradiol and cyproterone acetate in oral contraceptives on leukocyte migration through endothelial cell monolayers. DESIGN Experimental in vitro prospective study. SETTING An academic research laboratory. INTERVENTION(S) Endothelial cells were cultured on microporous membranes to produce monolayers. Polymorphonuclear leukocytes were used in a previously described migration assay (n = 7). The amount of untreated polymorphonuclear leukocytes that migrated through untreated endothelial cell monolayers was used as a control and set at 100%. In addition, a leukocyte adhesion assay was used. MAIN OUTCOME MEASURE(S) Leukocyte adhesion to and transmigration through endothelial cell monolayers. RESULT(S) Ethinyl estradiol and cyproterone acetate inhibited the migration of polymorphonuclear leukocytes through endothelial cell monolayers significantly (67% +/- 6.4%) when both cell types were treated to simulate in vivo conditions. The adhesion assay produced similar results. CONCLUSION(S) Ethinyl estradiol and cyproterone acetate were identified as potent inhibitors of leukocyte migration through endothelial cell monolayers.

Prenatal effects of betamethasone-L-carnitine combinations on fetal rat lung

Lungs of fetal rats between the 18th and 20th gestational day (total gestation lasting 22 days) were examined. There was a significant increase (p < 0.01) of the dipalmitoyl phosphatidylcholine content from day 19 to day 20 of gestation. In the second trial, pregnant rats were treated with different doses of betamethasone, L-carnitine, betamethasone-L-carnitine combinations, and saline (controls) for three days before Cesarean section on the 19th gestational day. Maternal injections of 0.10 mg/kg body weight betamethasone and 100 mg/kg body weight L-carnitine significantly (p < 0.05, p < 0.01 respectively) increased the dipalmitoyl phosphatidylcholine content of fetal lungs. Combinations of either 0.05 or 0.10 mg/kg body weight betamethasone with 100 mg L-carnitine also significantly increased the dipalmitoyl phosphatidylcholine content of the fetal lungs above control values (p < 0.001) and values achieved with betamethasone alone (p < 0.05). Maternal treatment with a betamethasone-L-carnitine combination on day 19 of gestation resulted in dipalmitoyl phosphatidylcholine levels comparable to those found on the 20th gestational day during normal lung maturation. Fetal rats delivered on the 20th gestational day survived, while fetuses delivered on the 19th gestational day did not survive.

Is CA-125 monitoring useful in patients with epithelial ovarian carcinoma and preoperative negative CA-125 serum levels?

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.

Femara®: der neue Aromatasehemmer

Ziel aller hormonellen Behandlungsmassnahmen ist die Ausschaltung der östrogenbedingten Wachstumsstimulation von Tumorzellen. Dies ist durch Suppression der Östrogenproduktion, durch Medikamente, die die Östrogenrezeptoren besetzen, ohne östrogene Wirkung auszuüben, und durch Reduktion der zellulären Östrogenrezeptoren möglich. Aromatasehemmer unterdrücken die zelluläre Umwandlung von Androstendion zu Östron. Androstendion wird in der Nebennierenrinde gebildet und kann in den peripheren Geweben, auch im Tumorgewebe, zu Östron umgewandelt werden. Dieser Stoffwechselweg stellt die Hauptquelle der Östrogenproduktion postmenopausaler Patientinnen dar. Die Gruppe der Aromatasehemmer hat während der letzten Jahre einen festen Platz in den Therapiekonzepten für Patientinnen mit hormonabhängigen, metastasierenden Mammakarzinomen einnehmen können. Neue Aromatasehemmer wie Letrozol oder Anastrozol lassen die Steroidsynthese in der Nebenniere weitgehend unbeeinflusst.