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Biomedical subjects

P Sevelda

Publications and source records attributed to P Sevelda.

At least 55 records · Page 3Linked to original sources

Preoperative CA 125: an independent prognostic factor in patients with stage I epithelial ovarian cancer.

OBJECTIVE: To evaluate the prognostic importance of preoperative CA 125 levels in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I epithelial ovarian cancer in comparison with the established prognostic factors: degree of differentiation, FIGO substage, and age. METHODS: In a retrospective analysis, the traditional prognostic factors and CA125 levels (cutoff value 65 U/mL) were studied in 201 patients who were treated in five centers during 1984-1993. Patients with borderline tumors or non-epithelial ovarian carcinomas were excluded, as were women in whom CA 125 had not been determined preoperatively. RESULTS: In univariate analysis (Mantel test), overall survival decreased significantly in patients positive for CA 125 (P < .001). Substage (P = .004) and histologic grade (P = .01) also significantly influenced survival prognosis. When the effects of preoperative CA 125 levels were correlated with histologic grade, all three subgroups with CA 125 levels equal to or greater than 65 U/mL were associated with a decreased survival probability (grade 1, P = .04; grade 2, P = .003; grade 3, P = .01). Multivariate analysis (Cox model) identified preoperative CA 125 as the most powerful prognostic factor for survival (P < .001), the risk of dying of disease being 6.37 times higher (95% confidence interval 2.39-16.97) in CA 125-positive patients. Although FIGO substage retained its significant influence on survival (P = .03), histologic grade and age were not prognostically important. CONCLUSION: Randomized trials investigating the efficacy of adjuvant treatment in patients with FIGO stage I epithelial ovarian cancer should also include stratification by preoperative CA 125 levels.

Age Factors↗

Randomised phase II study of epirubicin-vindesine versus mitoxantrone-vindesine in metastatic breast cancer.

The purpose of this study was to compare the activity and toxicity of epirubicin-vindesine (EV) with mitoxantrone-vindesine (MV) in patients with metastatic breast cancer. A total of 295 patients was randomly allocated to treatment with vindesine 3 mg/m2 combined with either epirubicin 40 mg/m2 or mitoxantrone 10 mg/m2. All drugs were given by intravenous push, treatment cycles were repeated at 3-4 week intervals. 255 patients were available for response, and 283 for toxicity. EV and MV yielded similar objective response rates (34 and 26%, respectively), response durations, times to progression and survival. Median time to remission was 1.8 and 3.1 months (P = 0.006) with EV and MV, respectively. In patients with visceral metastases, response rate was higher with EV than MV (40 versus 23%; P = 0.03). Patients receiving MV had less nausea/vomiting (P = 0.007) and alopecia (P = < 0.001) of WHO grade > or = 2. Bone marrow, cardiac and other toxicities were mild with both treatments. The observed differences in activity and toxicity between the two regimens appear to have clinical relevance. EV proved to be more active in visceral disease and to be able to induce remissions more rapidly. Accordingly, patients with visceral metastases or severe tumour-related symptoms may benefit from epirubicin-based treatment. Subjective toxicities, i.e. nausea/vomiting and alopecia, were less frequent and severe with MV. Thus, MV may prove useful in patients with more indolent disease and appears to warrant phase III evaluation in such patients.

Adult↗

[The prognostic effect of scintigraphy-guided lymphadenectomy in therapy of stage Ib cervix carcinoma].

In a retrospective study the survival rates of 161 patients with stage Ib cervical cancer after radical operation (Latzko, Wertheim-Meigs) including complete or incomplete pelvine lymphadenectomy were compared. To increase radicality of lymphadenectomy, preoperative targeting of pelvic lymph nodes was done in all the patients using 99mTc-Sb2S3 radiocolloid. Intraoperatively, a gamma-camera being integral part of an operating table allowed delineation and scintigraphy-guided resection of pelvic lymph nodes. Dependent on the evidence of remaining pelvine foci of radioactivity at the end of the operation, lymphadenectomy was assessed as complete or incomplete. Mean observation time of completely lymphadenectomised patients (n = 117,72.67%) were 80 months (5-169 months) and 42 months (1-149 months) of the incompletely lymphadenectomised patients (n = 44,27.33%). In 28 (23.93%) completely lymphadenectomised patients against only 5 (11.36%) patients with incomplete lymphadenectomy, lymph node metastases were proved histologically. Five year-survival rate of completely lymphadenectomised patients was 85.47% and 88.64% of incompletely lymphadenectomised patients (not significant, Mantel-Test). Also, selective comparison of lymph node-positive patients did not suggest a divergent trend indicated by 13 (46.43%) deaths of completely and 3 (60.0%) deaths of the incompletely lymphadenectomised patients after an observation of five years. The technique of scintigraphy-guided pelvic lymphadenectomy using 99mTc-Sb2S3 radiocolloid cannot be expected to improve prognosis of patients with cervical cancer stage Ib.

Adenocarcinoma↗

[The future of surgical gynecology: from dogma to science--from science to practice standard].

In the future of gynecologic surgery, there will be a reduction of traditional and an increase of endoscopic surgery. Development, progress, and realization of new technologies have to be based on scientific results, as it has been shown for the surgery of early-stage ovarian cancer. Endoscopy is already part of daily routine surgery in nearly all gynecologic departments, although important questions like the optimal technique, proper indications, and the consequences of these new technologies regarding the course of ovarian cancer are still not answered. Especially gynecological surgery has to turn away from a dogmatic way of thinking to a critical science-oriented practice in the future.

Female↗

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.

Acylation↗

Three-dimensional video-endoscopy: clinical use in gynaecological laparoscopy.

We describe a system that displays the abdominal organs in three dimensions during laparoscopy. The system consists of a single-rod-lens endoscope and two integrated microchip cameras. The surgeon has to wear active-liquid-crystal shutter-glasses to obtain a three-dimensional impression during the operation. Improved orientation in the abdominal cavity allows exact handling of surgical instruments. The three-dimensional system permits surgery with more accuracy, speed, dexterity, and safety than conventional two-dimensional systems.

Female↗

[Tumor vascular invasion in breast carcinoma. Hematoxylin-eosin versus immunohistochemical staining for factor VIII antigen].

Blood vessel invasion was investigated with haematoxylin-eosin (HE) staining and immunohistochemical staining for factor VIII antigen (F VIII) in 106 patients with primary carcinoma of the breast, in order to compare their value in prognosticating the probability of recurrence. Blood vessel invasion was diagnosed in 65 cases (61.9%) by HE, but in only 45 (43.4%) by F VIII staining. Lymph-node status and blood vessel invasion correlated positively on HE (r = 0.73; P = 0.0001), but not so on F VIII staining. Multivariate logistic regression showed blood vessel invasion to be a strongly independent prognostic factor for recurrence-free survival with F VIII staining (odds ratio: = 7.19; P = 0.0001), while HE staining was not independent from other prognostic factors. These preliminary data thus suggest that demonstrating vascular invasion by F VIII staining may identify those patients with a very high risk of recurrence, independent of lymph-node status.

Adult↗

Prognostic significance of cell DNA content in early-stage ovarian cancer (FIGO stages I and II/A) by means of automatic image cytometry.

Paraffin-embedded material from 69 patients with epithelial ovarian cancer FIGO stages I and II/A (including 21 patients with borderline carcinoma) was studied with automatic DNA image cytometry. Univariate analysis indicated a significant difference in survival based on the presence of nuclei with high DNA content (higher than 5 C). A group of patients with less than 0.2% cells with high DNA content had a 6-year survival of 87%, whereas in a group of patients with more than 0.2% of such cells, 6-year survival was 49%. This parameter remained significant when used in a group of stage I/a and I/b patients. Statistical analysis of diploid vs. non-diploid tumors also showed significant difference in survival. Separate analysis of 48 invasive ovarian cancers indicated that ploidy, the percentage of cells with high DNA content and tumor stage (stage I/a + b vs. stages I/c + II/a) reached significance for survival, whereas grading did not. In addition, comparison of clinical stage, grading, ploidy and the percentage of cells exceeding 5 C with a threshold at 0.2% by means of a multivariate analysis (Cox regression model) showed that only the percentage of cells exceeding 5 C remained statistically significant.

Adult↗

A comparative analysis of management and prognosis in stage I and II fallopian tube carcinoma and epithelial ovarian cancer.

Staging and surgical as well as post-operative treatment of primary Fallopian tube carcinoma (FTC) followed the lines established for primary ovarian cancer (OC). In a nationwide retrospective analysis we were able to find a distinct difference between these two tumours. A total of 262 patients, 68 with FTC and 194 with OC, in stage I and II were included into this study. A univariate as well as a multivariate analysis for survival was performed, including factors such as age, histological type, grading and surgical and adjuvant treatment. A significantly poorer outcome (P = 0.0002) for FTC patients with a 5-year survival of 50.8% compared with 77.5% for OC patients was observed. This finding was persistent and independent of any investigated factor, in univariate as well as multivariate analyses. Therefore, we feel that a more aggressive therapeutic approach to the treatment of FTC even in early stages can be recommended. On the other hand, the retrospective character of our study has to be taken into account.

Age Factors↗

[The value of the "vascular invasion" factor for prognosis of breast cancer].

The histological sections of 106 patients, who underwent a primary breast cancer operation in the years 1986 and 1987, were inspected for the presence of tumour vascular invasion. With immunohistochemical methods, tumour vessels were tomographed and the paraffin sections were stained with an antibody, which is sensitive to factor VIII-antigen. A tumour embolus was considered present, if a malignant cell was established within a positively stained lumen. The question of possible influence on the pathogenesis of breast cancer was examined in case of vascular invasion in the histological preparation. In 46 of the 106 patients (43.4%), tumour emboli were found. After an average observation period of 59 months, no tumour progression was seen in 60 patients, 46 patients developed a recurrence of the tumour at the check-up date. The presence of vascular invasion correlates with undifferentiated tumour grading. The probability of relapse- free survival after 5 years was 83.9% within the group without vascular invasion, compared with 47.9% (p = 0.0001) within the group with established vascular invasion. In the multivariate analysis of the factors lymphonodular status, grading and vascular invasion, it was found, that the presence of tumour vascular invasion with a relative risk of 3.68 (95% CI 1.93-7.03) was the strongest statistically significant prognostic factor for relapse-free survival (p = 0.0001).

Adult↗

[Conisation in stage Ia cervix cancer].

Between 1975 and 1988, a total of 78 patients suffering from cervical cancer stage Ia were treated by conisation based on a positive smear. According to FIGO, these 78 patients consisted of 53 (67.9%) stage Ia1 and 25 (32.1%) stage Ia2 cases. Complete removal of the tumour by conisation was achieved in 51 patients. In 23 cases (29.5%) the margin of resection was reached by a carcinoma in situ, in 4 cases (5.1%) invasive carcinoma was found. Conisation was not followed by further surgery in 10/51 patients with complete tumour removal. One patient (1/23) with incomplete removal underwent surgery elsewhere. In the other 67/78 patients following hysterectomy, the pathologist diagnosed three cases of cervical cancer, 11 cases of carcinoma in situ and 53 cases (67.9%) without pathological findings. Carcinoma in situ after hysterectomy was found in only 2 cases (4.9%) with primarily free resection margins of the conus. Among the 27 patients with carcinoma in situ or invasive carcinoma reaching the conus margin, 9 cases of carcinoma in situ and 3 invasive carcinomas were diagnosed histologically after hysterectomy and one patient underwent surgery elsewhere. In this study, the value of conisation as single therapy of cervical cancer stage Ia1 and stage Ia2 with good prognosis (depth of infiltration of < 3 mm and no invasion of blood vessels) is discussed and the importance of thorough and exact histological examination is emphasised.

Adult↗

Antenatal betamethasone-dose-effects on fetal rat lung morphology and surfactant.

Pregnant rats received betamethasone 0.02, 0.05, 0.10, or 0.20 mg/kg body weight/day or saline (controls) for three days before delivery of fetuses at day 19 of gestation. Dose related effects on morphology, dipalmitoyl phosphatidylcholine content, and phosphatidylcholine species composition of the fetal lungs were evaluated. Injection of 0.02 and 0.05 mg/kg body weight betamethasone resulted in cellular differentiation of some cells, but the increase in dipalmitoyl phosphatidylcholine content was not significant. Dosages of either 0.10 or 0.20 mg/kg body weight resulted in markedly accelerated organ differentiation, complete cytodifferentiation of type II cells, and markedly increased numbers of lamellar bodies per alveolar type II cell. Compared to the controls, maternal administration of 0.10 or 0.20 mg/kg betamethasone caused significant increases of both fetal lung dipalmitoyl phosphatidylcholine content, and the fraction of dipalmitoyl phosphatidylcholine of total phosphatidylcholine. None of the parameters differed between the groups that were treated with 0.10 or 0.20 mg/kg body weight betamethasone respectively. Diminution of lung DNA content was significant after treatment with betamethasone in doses of 0.05, 0.10, and 0.20 mg/kg body weight. The results of the present study suggest that maternal treatment with lower doses than those in common usage may be successful in prevention of respiratory distress syndrome, and that higher dosages do not confer any additional advantage.

1,2-Dipalmitoylphosphatidylcholine↗

[Tumoral vascular density in breast tumors and their effect on recurrence-free survival].

Angiogenesis quantitation of 106 patients with primary breast cancer and 35 patients with adenofibroma of the breast was compared and examined to its prognostic relevance for five-years disease-free survival in breast cancer patients. Immunocytochemical staining for Factor VIII-related antigen was performed to outline vascular endothelium. We found a significant higher vessel density in breast cancer patients who experienced recurrence (17.4) than in those with no recurrence (9.4) or with adenofibroma (8.7) [p < 0.0001]. The probability of five-years recurrence-free survival for patients with a primary tumor of high vessel density was at 52.3% and 86.4% for tumors of low microvessel density (p < 0.0011). Microvessel density proved to be an independent prognostic factor for breast cancer recurrence in the Cox-Model (relative risk 2.047, p = 0.0002).

Biomarkers, Tumor↗

In vitro and in vivo evaluation of the combination of cisplatin and its analogue carboplatin for platinum dose intensification in ovarian carcinoma.

BACKGROUND: Cisplatin and its analogue carboplatin have been shown to cause dose-dependent growth inhibition throughout a wide dose range in the ovarian cancer cell lines OVCAR-3, 2780, HTB-77, and CRL-1572 tested. Cisplatin was 30 times more effective than carboplatin. The combination of both substances led to a less-than-synergistic effect, as was revealed by an isobologram in the OVCAR-3 cell line. Because of the different toxicity pattern, cisplatin and carboplatin theoretically are ideal candidates for combination chemotherapy in platinum-sensitive tumors. METHODS: In a Phase II study, the efficacy, the toxicity profile, and the feasibility of combining both substances were assessed in 20 previously untreated patients with ovarian cancer. The regimen consisted of carboplatin (300 mg/m2) on day 1, followed by cisplatin (100 mg/m2) on day 2 every 4 weeks. RESULTS: A total of 81 cycles were administered (median, 4 cycles; range, 1-6 cycles); four patients experienced complete remission and three experienced clinical partial remissions. Limiting toxicities were thrombocytopenia, leukopenia, and ototoxicity. The mean (+/- standard deviation [SD]) carboplatin and cisplatin dose intensities (DI) reached during the first four cycles of therapy were 58 mg/m2/week (+/- 18 mg/m2/week) and 21 mg/m2/week (+/- 7 mg/m2/week), respectively, which corresponded closely to the projected DI of 75 and 25 mg/m2/week, respectively. Based on the equivalence ratio of 4:1, the DI of carboplatin has been converted into the respective cisplatin DI, resulting in a total DI estimate. The overall DI of 37 mg/m2/week (+/- 14 mg/m2/week) was close to the projected one of 44 mg/m2/week. CONCLUSIONS: Combining cisplatin with carboplatin was found to represent a feasible and efficacious therapeutic strategy for increasing platinum dose intensity.

Anemia↗

Serum prostaglandin F2 alpha (PGFM) and oxytocin levels correlate with sonographic changes in the cervix in patients with preterm labor.

This is a study on the correlation of maternal serum oxytocin and prostaglandin F2 alpha (PGFM) levels with sonographically measurable changes in the cervix and the internal cervical os in patients with preterm labor. Oxytocin levels significantly correlate (P = 0.03) with the width of the internal os and the PGFM values significantly correlate with the length of the cervix (P = 0.008). An increase in the oxytocin level resulted in a measurable widening of the internal os and an increase in the prostaglandin level resulted in a measurable shortening of the cervix.

Cervix Uteri↗