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Biomedical subjects

M Lahousen

Publications and source records attributed to M Lahousen.

At least 37 records · Page 2Linked to original sources

Randomized trial of recombinant human interleukin-3 versus placebo in prevention of bone marrow depression during first-line chemotherapy for ovarian carcinoma.

PURPOSE: To determine whether recombinant human interleukin-3 (rhIL-3) reduces bone marrow depression and improves chemotherapeutic schedule adherence in ovarian cancer patients receiving first-line combination chemotherapy. PATIENTS AND METHODS: In a randomized multicenter study, 185 patients received carboplatin (dose based on projected area under the concentration-time curve [AUC]=4) and cyclophosphamide (750 mg/m2) day 1, every 3 weeks for six cycles. Patients were randomized to receive rhIL-3 (5 microg/kg) or placebo once daily subcutaneously on days 3 to 12. RESULTS: Adherence to chemotherapeutic regimen, mean chemotherapy cycle length, tumor response rate, and median survival at 24 months did not differ between groups. The number of side effects-primarily allergic reactions, flu-like symptoms and fever-were higher in the rhIL-3 group, which resulted in 21 discontinuations compared with one in the placebo group. Compared with placebo, the rhIL-3 group had higher platelet counts day 1 of cycles 2 to 6. The number of patients with World Health Organization (WHO) grade IV thrombocytopenia or number of platelet transfusions did not differ. Leukocyte counts differed only in cycles 1 and 2 between groups. The leukocyte nadir occurred earlier in the rhIL-3 (day 12) than in the placebo group (day 15, P=.006). Leukocytes and neutrophils were only higher in the rhIL-3 group day 1 of cycle 2. In cycles 4 and 5, more patients with WHO grade IV neutropenia received rhIL-3 (P < .005). Eosinophil counts were higher day 1 of cycles 2 to 6 in the rhIL-3 group (P < .0001). CONCLUSION: rhIL-3 had stimulatory hematopoietic effects. This did not result either in reduction of platelet transfusions or in improvement of chemotherapeutic schedule adherence. There were more side effects in the rhIL-3 group than in the placebo group. rhIL-3 at 5 microg/kg/d is, therefore, not of clinical benefit in this chemotherapeutic regimen.

Adult↗

Tumor angiogenesis as a prognostic factor in ovarian carcinoma: quantification of endothelial immunoreactivity by image analysis.

BACKGROUND: The growth of a malignant tumor requires the formation of new capillaries. Quantification of these microvessels is difficult. The purpose of this study was to establish an objective technique for quantifying angiogenesis and to evaluate whether microvessel quantity may predict tumor aggressiveness in patients with ovarian carcinoma. METHODS: Endothelial area was used to quantify microvessel density in immunohistochemically stained sections of 28 International Federation of Gynecology and Obstetrics Stage IIIC ovarian carcinomas. The endothelial area was measured with a computer-aided image analysis system in the subepithelial stroma of highest vascularization. The endothelial area in the specimens of 14 patients who survived for > or =6 years was compared with that of 14 patients matched for stage and treatment who died of the disease. RESULTS: The mean tumor area analyzed was 5.04 +/- 0.23 mm2. The mean endothelial area per mm2 of stroma from survivors and dead patients was 0.038 +/- 0.026 mm2 and 0.110 +/- 0.034 mm2, respectively (P < 0.0001). No significant differences were found in histology, tumor grade, status of lymph nodes, and amount of residual tumor. CONCLUSIONS: Image analysis was used to overcome the potential subjectivity of manual counts. Computer-assisted image analysis can evaluate accurately the angiogenic potential in ovarian carcinomas. Tumor angiogenesis may prove to be a prognostic factor in patients with ovarian carcinoma. This study suggests that the measurement of the endothelial area would be clinically useful in determining microvessel density [See editorial on pages 2219-21, this issue.]

Antigens, CD34↗

Erythropoietin treatment under polychemotherapy in patients with gynecologic malignancies: a prospective, randomized, double-blind placebo-controlled multicenter study.

In order to examine the influence of erythropoietin (rHuEPO) on serum hemoglobin levels, transfusion requirements, and quality of life in patients with gynecologic malignancies under polychemotherapy and chronic tumor anemia (hemoglobin <11 g/dl), we performed a prospective, randomized, double-blinded placebo-controlled clinical trial. Between October 1992 and October 1993, 35 patients from 5 gynecologic departments were entered into this trial. Inclusion criteria were hemoglobin level <11 g/dl, ferritin level >29 ng/ml, stool negative for occult blood, and life expectancy for more than 3 months. Patients received either 150 U/kg body wt rHuEPO (Erypo by Cilag-Janssen) sc three times a week for 12 weeks (n = 23) or a placebo (n = 12). If the hemoglobin levels of the 4th, 8th, or 12th week were >2 g/dl above the baseline value and/or >12 g/dl, the patient was classified as a responder. Patients who required blood transfusions (hemoglobin <8 g/dl, erythrocytes <3 x 10(6)/ml, or clinical symptoms of anemia) were classified as nonresponders. A nonvalidated quality of life questionnaire was completed by the patient at the beginning of the treatment and then every fourth week before receiving chemotherapy. In the rHuEPO group 56.6% of the patients responded to the treatment (chi2 = 10.79, P = 0.001) and only 5 patients (21.7%) required blood transfusions, whereas 8 of 12 patients in the placebo group (66.6%) had to be transfused (chi2 = 6.81, P = 0.009). Quality of life did not differ significantly between the rHuEPO group and the placebo group of patients. Within the rHuEPO group those patients that responded showed a significant increase in physical activity after response in comparison to the preresponsive phase (P = 0.02, paired t test). We therefore concluded that rHuEPO significantly increases serum hemoglobin levels and decreases transfusions requirements while maintaining quality of life in patients with gynecological malignancies who are undergoing polychemotherapy.

Adult↗

Prognostic factors in cervical cancer.

The inadequacy of clinical methods has spurred efforts to develop objective, measurable and reproducible parameters for the spread and growth behaviour of cervical cancer. Morphological methods were applied first. They can be used only on the surgical specimen, but are accessible to biometry. The presented results are based on 479 surgical specimens obtained at radical abdominal hysterectomy for cervical cancers of different sizes. The specimens were processed as frontal giant sections with the cervix, the vaginal cuff and the parametria on both sides. The median follow-up time was 7-8 years. Statistical correlations were found between follow-up data, biometric morphologic criteria and survival. The statistical ranking of the significant prognostic factors produced the following order: lymph node metastases, size of lymph node metastases, tumour volume, parametrial involvement and vascular invasion.

Cell Differentiation↗

Primary serous papillary carcinoma of the peritoneum: a report of 18 patients.

Eighteen patients with primary papillary serous carcinoma of the peritoneum (PPSCP) were treated at the Department of Obstetrics and Gynecology of the University of Graz between 1980 and 1996. Primary tumours from other sites, particularly the pancreas and ovary, had been excluded. Because of extensive spread of the disease particularly in the upper abdomen, seven of the 18 patients (38%) underwent exploratory laparotomy only. Median overall survival time was 10 months (range 1-28+). This figure reflects the extent of spread of the disease at diagnosis on one hand, and that optimal cytoreductive surgery (residual disease < or = 2 cm) was possible only in six of the 18 patients (33%) on the other. The six patients with optimal cytoreduction had a better survival (range 4+ to 28+ months) than those who underwent less radical surgery. These data indicate, that, similar to primary ovarian cancer, the amount of residual disease may be an important prognostic factor in patients with PPSCP.

Adult↗

Selective decrease in serum immunoglobulin G1. A tissue nonspecific tumor marker detecting early stages of gynecologic malignant disease with high efficiency.

BACKGROUND: Malignant diseases of various tissue origin have previously been found to be associated with a characteristic shift in the serum pattern of IgG subclasses, i.e., a highly significant reduction of the percent of IgG1 and an increase of the percentage of IgG2 relative to the total IgG. In the present study we examined the diagnostic performance of this indirect tumor marker in patients with carcinomas of various sites within the female reproductive tract. METHODS: Using quantitative affinity chromatography, the percents of IgG1 and IgG2 in the total IgG were determined for 207 patients with carcinoma of the ovary, cervix, or corpus uteri, prior to any treatment. The data were compared with those of 135 age matched healthy females and 52 patients with benign gynecologic diseases. RESULTS: It was found that (1) mean values for the percents of IgG1 and IgG2 of all of the cancer patients differed significantly from those of the patients with benign disease and healthy controls; (2) no differences were noted between carcinomas of the ovary, corpus or cervix uteri; (3) early stages of carcinoma exhibited the effect to the same extent as late stages; (4) the specificity of the percent of IgG1 to discriminate between controls and cancer patients ranged between 90 and 100%, regardless of localization and stage of tumor; and (5) whereas with ovarian cancer CA 125 showed a slightly greater sensitivity, the percent of IgG1 was by far more sensitive than the conventional markers CA 125, TPA, CEA, Ferritin, and SCC to diagnose carcinoma of the cervix and corpus uteri, notably at early stages. Combined analysis of the percent of IgG1 and CA 125 and/or TPA led to an increase in sensitivity with tumors of all three sites. CONCLUSIONS: Thus, the determination of the percent of IgG1 by itself and/or in combination with conventional markers may provide relevant information regarding the noninvasive detection of early stages of gynecologic carcinoma.

Adult↗

[Diagnostic value of combined vaginal ultrasound and hysteroscopy in peri- and postmenopausal bleeding].

OBJECTIVE: Is it possible to reduce the rate of curettages by using ultrasound and hysteroscopy? METHODS: Transvaginal sonography, hysteroscopy, and dilation and curettage were performed in 103 patients with menometrorrhagia or postmenopausal bleeding. The patients were divided into three groups, depending on the ultrasound findings. RESULTS: All 9 cases with cancer of the endometrium were found in group 3. 1 of the 9 carcinomas was not detected by hysteroscopy. CONCLUSIONS: We believe that dilation and curettage is necessary in symptomatic women with an endometrial thickness < 4 as well as > 4 mm. Prospective studies have to clear the question of whether endometrial carcinomas can be detected by hysteroscopy in cases with an endometrium < 4 mm thick.

Diagnosis, Differential↗

[Value of ultrasound in early detection of endometrial carcinoma].

OBJECTIVE: The purpose of our study was to examine the diagnostic value of the biometry of the endometrium for the early detection of endometrial carcinomas in postmenopausal women as well as to compare our results with those of other authors. METHODS: In 69 post menopausal women the endometrial thickness measured by vaginosonography before diagnostic curettage or hysterectomy was compared with the histological results. RESULTS: Using a cutoff value of 6 mm, a sensitivity of 96%, a specificity of 24%, a positive predictive value of 16%, and a negative predictive value of 97% were established. CONCLUSIONS: Endovaginal ultrasound evaluation of the endometrial thickness is not specific enough to be used screening method for the early detection of endometrial carcinoma.

Aged↗

[Early invasive cervix carcinoma--FIGO 1994].

7078 histological cases of cold-knife conisation have been reevaluated. Because of the changes of the FIGO 1994 staging system, all microinvasive cancers in that material have been reclassified. This had major histomorphological and clinical consequences.

Cervix Uteri↗

Prognostic impact of DNA content and AUER classification in primary fallopian tube carcinoma.

DNA ploidy has been studied in 61 primary fallopian tube carcinomas using image-cytometry. The investigation also included survival analysis, and ploidy classification according to AUER was performed in order to evaluate its prognostic impact for fallopian tube carcinoma. A high number of aneuploid cases were observed (79% aneuploid vs. 21% euploid tumors). The high incidence of aneuploid tumors was consistently observed among all FIGO-stages as well as all groups of histologic grading. There was no correlation between ploidy and FIGO-stage or histologic grading. Patients with euploid DNA content showed a median survival of 34 months compared to 24 months for aneuploid cases (log-rank, P = 0.83). No correlation between the AUER classification and FIGO-stage or histologic grading could be observed. Tumors with an AUER type I and II (75th quantile 41 months) showed a better outcome than tumors with AUER III and IV (75th quantile 19 months). Although these results did not reach statistical significance (P = 0.07), a trend could be observed. Therefore AUER classification may be useful as an objective prognostic parameter. The high incidence of aneuploid tumors could be an expression of the high biologic aggressiveness of primary fallopian tube cancer which has been repeatedly mentioned in the past.

Adenocarcinoma↗

[Granisetron, a antiemetic for treatment of cytostatic drug-induced vomiting: results of a practice-oriented study].

The present multicentre Austrian investigation of the prophylactic intravenous administration of granisetron, a serotonin antagonist, routinely for control of cytostatic-induced nausea and emesis was carried out in 102 patients with cancer of various types undergoing different emetogenic cytostatic regimens (232 cycles of chemotherapy). A major therapeutic response, i.e. maximally one vomit over the first 24 hours, was achieved in 78-90% of patients undergoing a single or multiple day regimen of chemotherapy. Delayed emesis, experienced between day 1 and day 4 after chemotherapy, was observed in < 5% of the patients. However, particularly in single day regimens 25% of the patients showed only a moderate response to granisetron in suppressing delayed emesis. Tachyphylaxis to granisetron therapy was not observed in the first 3 consecutive cycles of chemotherapy. The individual global efficacy of emesis control by granisetron (day of chemotherapy over all cycles plus the following 7 days) was very good. An excellent therapeutic response was seen in 53-55% of all cases. The study also demonstrated the economic advantages of granisetron therapy. In the majority of patients (88/102) only a single dose of granisetron (3 mg) was required. The tolerability was also very good. The main adverse events reported were headache (7.8%) and constipation (4.9%).

Adult↗

Solitary metastasis in the tarsus preceding the diagnosis of primary endometrial cancer. A case report.

A solitary metastasis in the left tarsus led to the diagnosis of primary endometrial cancer in a 61 year-old patient with no history of postmenopausal bleeding. Lower leg amputation, total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and paraaortic lymphadenectomy were performed. Histopathology showed a well-differentiated endometrioid adenocarcinoma of the uterus with a low mitotic rate, but infiltration of the outer third of the myometrium and lymph vessel invasion (FIGO Stage IVb). Immunostaining was positive for progesterone receptors, but negative for estrogen receptors and p53. The lymph nodes were free of metastases. Ascites was positive for malignant cells. Postoperatively the patient received carboplatin, cyclophosphamide and medroxyprogesterone acetate and is alive with no evidence of disease 10 months after diagnosis.

Adenocarcinoma↗

[Modification of liver parameters by adjuvant administration of proteolytic enzymes following chemotherapy in patients with ovarian carcinoma].

In a single-blind placebo controlled trial with 3 parallel groups the effects of concomitant administration of proteolytic enzymes (either tablets or dragees) on the influence of the liver parameters to a carboplatinum chemotherapy were investigated. 59 female patients were enrolled into this study after ovarial cancer surgery. Out of these 59 patients 23 were allocated to the placebo group, 24 to the tablet form and 12 to the dragees preparation. The study medication was administered from day 2 to 7 after each of the 6 chemotherapy cycles in monthly intervals in a dosage of 2 tablets t.i.d. placebo, 2 tablets t.i.d. Wobe-Mugos and 10 dragees t.i.d. The main efficacy criteria for the adjuvant study treatments were SGOT, SGPT, Gamma-GT, alkaline phosphatase and lactate dehydrogenase. The data of these parameters indicate an overall beneficial effect in patients in both of the verum groups compared to placebo and provide--in combination with other safety data documented in this study--evidence, that the concomitant administration of Wobe-Mugos does not negatively affect the overall tolerability.

Adolescent↗

DNA ploidy in primary fallopian-tube carcinoma using image cytometry.

Determination of DNA ploidy in 61 samples of primary Fallopian-tube carcinoma (FTC) by use of image cytometry is presented. Of these samples, 48 showed an aneuploid DNA content. Patients with euploid DNA content showed a median survival time of 33.8 months compared to 24.5 months for aneuploid cases. A high incidence of aneuploid tumors was consistently observed among all FIGO stages and in all groups of histologic grading. However, no correlation between ploidy and FIGO stage or histologic grading could be demonstrated. This observation could be regarded as a marker for the high aggressiveness of FTC which has been repeatedly described in the past.

Adult↗

Prognostic factors in primary fallopian tube carcinoma. Austrian Cooperative Study Group for Fallopian Tube Carcinoma.

A retrospective nationwide evaluation of primary fallopian tube carcinomas for a period of 10 years (1980-1990) was performed to evaluate the prognostic impact of various factors. Sixty-six cases were investigated for the prognostic influence of estrogen (ER) and progesterone (PgR) status, mitotic activity, degree of nuclear anaplasia, and inflammatory reaction. ER and PgR receptors were detected by immunohistochemistry from paraffin sections. Forty-two percent were PgR-positive and 26% were ER-positive. However, no correlation of steroid receptors with survival could be found. Ninety-two percent of all tumors showed a moderate and high degree of nuclear anaplasia and only 8% showed a low degree of nuclear anaplasia. Thirty-four (52%) samples from all patients revealed low mitotic activity compared to 32 (48%) with an intermediate and high mitotic rate. Twenty-four (37%) tissue samples showed a positive inflammatory reaction which correlated with a significantly better outcome compared with tumors without this feature. This finding was also confirmed in multivariate analysis as an independent prognostic factor.

Fallopian Tube Neoplasms↗

Lymphogenous metastasis in the primary carcinoma of the fallopian tube.

The bad prognosis of primary Fallopian tube carcinoma (FTC) is mostly ascribed to early lymphogenous metastasis. Yet, there is a lack of information on the tumor size at which lymph node metastasis must be expected to occur. Our study was therefore designed to correlate the anatomopathologic substratum and the histologic results with the lymph node status. Data were obtained from 21 women who received primary surgery, during which additional total pelvic and para-aortic lymphadenectomy was performed as well. The "surgical" staging was compared to the final clinical staging after histologic inspection of the lymph nodes according to the FIGO classification. Lymph node metastases never occurred as long as the tumor was confined to the tube (stage I). Lymphogenous dissemination set in only after further, local expansion of the tumor, involving the ovaries, the peritoneum, or the uterus (surgical stage II); 3 of the 7 patients of surgical stage II had to be reclassified to stage III because of manifest lymph node metastases. After the onset of intra-abdominal or general metastasis (stage IV), lymph node metastases occurred significantly more often (P = 0.048). Due to the specific lymphatic drainage, lymphogenous metastasis must be expected to spread as far as to the para-aortic region even in the early stages. Highly differentiated tumors (G I) do not disseminate into the lymphatic system, not even in advanced stages, whereas anaplastic tumors (G II and III) metastasize relatively early. As soon as metastasis has occurred, prognosis of life diminishes markedly, but not significantly (49 versus 24 months, P = 0.19). Correct FTC-staging is obtained only on the basis of pelvic and para-aortic lymphadenectomy.

Adolescent↗

Evaluation of adjuvant therapy after surgery for primary carcinoma of the fallopian tube.

OBJECTIVE: To evaluate the impact of postoperative therapy (chemotherapy vs. irradiation) on overall survival. DESIGN: A nationwide retrospective analysis. SETTING: Hanusch-Krankenhaus, Department of Gynaecology, SUBJECTS: 115 patients with histologically proved primary carcinoma of the Fallopian tube: 49 received six treatment cycles of a cis-platinum regimen (group I), 24 patients were treated by full irradiation using 50 Gray minimum (group II). The two groups had a similar distribution of stage I and II; in the more advanced stages chemotherapy was the predominant method of treatment. RESULTS: The five-year survival rate was 53% for women receiving irradiation as against 27% for those given cis-platinum. If the analysis was restricted to those patients with comparable stage I and stage II lesions, the p-value (0.07) was of borderline significance. There was no advantage in adding abdominal to pelvic irradiation (P = 0.62). CONCLUSIONS: Stage I and stage II carcinoma is probably better treated postoperatively by radiotherapy than chemotherapy. Chemotherapy may have more therapeutic potential in patients with more advanced lesions.

Adult↗