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Publications and source records attributed to N Vavra.
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Site of recurrence and histological type are significant prognostic factors for survival in recurrent endometrial carcinoma. The aim of this retrospective analysis of 56 patients suffering from recurrences of endometrial carcinoma following initial surgery was to establish the prognostic relevance that the following factors had on the survival rate: age, primary tumor stage, histological assessment (papillary vs non-papillary), postoperative adjuvant radiation therapy, recurrence free interval (< 24 months, > 24 months) and localisation of recurrence. The univariate analysis showed a significantly longer median survival time after recurrence for the following parameters: local recurrence vs extra vaginal recurrence (77.5 months vs 15.7 months, p = 0.02), non-papillary vs papillary carcinoma (36.1 months vs 7.7 months, p = 0.02), no adjuvant irradiation vs adjuvant irradiation (82.0 months vs 8.8 months, p = 0.007). Patients after adjuvant radiation treatment and patients suffering from papillary carcinomas have a significantly higher proportion of patients with distant metastasis (patients with adjuvant radiation treatment: Chi-square test: p = 0.001; patients suffering from papillary carcinomas: p = 0.033). In the case of local recurrences, a three year survival rate of 54% can be achieved with radiation treatment. Recurrences of papillary endometrial carcinomas and patients suffering from distant metastasis on the other hand, show very low survival rates if they are treated with radiation therapy (papillary carcinomas: three-year survival rate of 18%, patients suffering from distant metastasis: 19%). These patients should be included in randomised studies with a view to examining the therapeutic effects of either additional or exclusive treatment with chemotherapy.
In a retrospective analysis of 294 patients with FIGO stages III and IV epithelial ovarian cancer treated with different polychemotherapy regimens in two prospective randomised phase III trials between 1981 and 1988, we evaluated the importance of platinum dose intensity for survival. The median survival time of 55 patients who were treated without platinum was 11 months, whereas 205 patients who were treated with a polychemotherapeutic regimen with a platinum dose intensity of 8 mg/m2/week showed a median survival time of 26 months. Of 34 patients who were treated with a platinum dose intensity of 18 mg/m2/week, more than 50% are still alive and therefore the median survival time has not yet been reached (Mantel test p < 0.001). These findings support the hypothesis that an increase in platinum dose intensity during the first treatment regimen leads to an increase in survival of patients with advanced epithelial ovarian cancer. Since 1991 we have been investigating in a prospectively randomized clinical trial whether a combination of carboplatinum and cisplatinum with a planned dose intensity of 43.75 mg/m2/week is feasible and able to improve survival in comparison with standard polychemotherapy (cyclophosphamide/cisplatinum) with a planned dose intensity of 25 mg/m2/week. Evaluation of toxicity of 268 cycles of carboplatinum/cisplatinum in 58 patients showed that a platinum dose intensity of 33.4 mg/m2/week was achievable with acceptable toxicity. Results with regard to therapeutic efficacy of this high dose therapy are expected within the next year.
A precondition for the early diagnosis of ovarian cancer by means of raised tumour marker levels is high sensitivity at an early stage of the disease. In this study the relationship of the levels of the tumour marker CA-125 to the variables age, grading and histological status was examined in 52 patients with verified FIGO stage I epithelial ovarian cancer. A liminal value of 35 U/ml was accepted and the patients were split into 2 groups according to whether the tumour marker exceeded this value or not. The survival probability was calculated for each group in order to gauge the prognostic significance of this serum marker. Although there was no statistically significant correlation between the CA-125 levels established preoperatively and the above-mentioned variables, in contrast to other studies we found a higher overall sensitivity of 62%. Of particular interest is the considerably higher sensitivity of CA-125 in the postmenopausal patients within our collective. The findings of this study suggest that marker-positive patients might have a poorer survival prognosis.
The injection of different substances into early, unruptured tubal pregnancies is increasingly advocated. In this study, fertility was evaluated after treatment of tubal pregnancy by means of prostaglandins. The overall tubal patency rate was 86.4% and 14 of 20 patients (70%) could subsequently achieve pregnancy.
In the present study, plasma oxytocin and prostaglandin F2 alpha metabolite (PGFM) concentrations were measured in 46 patients admitted for preterm labour. Gestational age ranged from 20-34 weeks. Samples were collected 12 hours before and after initiation of tocolysis. Patients with a premature rupture of the membranes and/or intra-amniotic infection were excluded in this study. There was a significant difference in the oxytocin (p = 0.05) and PGFM levels (p = 0.007, after 12 hours: p = 0.004) between a control group without preterm labour and women with preterm labour. No differences were seen between the successfully treated (delivery more than 5 days after start of tocolysis) and the failure group. There was no significantly different increase or decrease in PGFM and Oxytocin plasma levels between treatment failures and successfully treated patients.
The present retrospective study attempts to evaluate the significance of factors such as age, histological type, histological grading, tumour size, lymph node metastases and tumour infiltration of the corpus uteri. Between 1975 and 1988, 312 patients were operated at our department or referred to postoperative radiotherapy. They fulfilled the inclusion criteria: histopathological stage Ib and radical hysterectomy with pelvic lymphadenectomy. The multivariate analysis confirmed, that the factors histological grading (G3 vs G1 + G2: relative risk (RR) = 2.66; 95% confidence interval (CI) = 1.36-5.18), tumour size (tumour infiltration of the cervix greater than 2/3 vs less than 2/3: RR = 2.36; 95% CI = 1.07-5.17), and pelvic lymph node metastases (positive vs negative: RR = 5.36; 95% CI = 2.70-10.65) are of significant importance for the survival. The results show, that patients with a cervical carcinoma in FIGO stage IB, with an infiltration of more than two thirds of the cervix with a more or less differentiation and with or without positive lymph node status, should be classified as high risk patients. In these unfavourable situations, a prospective randomised study should clarify the success rate of adjuvant therapy.
Several malignant neoplasms express high levels of epidermal growth factor receptors. The aim of this study was to assess whether 123I-labeled epidermal growth factor can concentrate in lymph node metastases of squamous cell carcinomas of the cervix. 14 patients with advanced cervical cancer were selected because of their high probability of lymph node metastases. Planar scintigrams were recorded from the lower and upper abdomen following subcutaneous injection of 123I-labeled epidermal growth factor into the web space of each foot. Scintigraphic images were interpreted without knowledge of computerized tomography scan (n = 13) and ultrasound (n = 9) results from the pelvic lymph nodes. In 2 patients, histological verification was performed by diagnostic biopsy of pelvic lymph nodes. Nodal involvement was confirmed by computerized tomography for 4 of the 11 positive scans and by ultrasound for 2. In 11 out of 14 patients an increased uptake of 123I-labeled epidermal growth factor could also be seen in the primary tumour. Our findings suggest that targeting of cervical cancer lymph node metastases can be achieved by in vivo binding of 123I-labeled epidermal growth factor with receptors on tumour cell surfaces.
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The present retrospective study attempts to evaluate the significance of adjuvant radiotherapy as a prognostic factor for stage Ib cervical carcinoma without lymph node metastases but with lymph-vascular space invasion. 54 patients fulfilled the inclusion criteria: histopathological stage Ib, radical hysterectomy with pelvic lymphadenectomy, negative pelvic lymph nodes and lymph-vascular space involvement. Though larger tumors were found (tumor infiltration of the cervix greater than 2/3) in the irradiated group (chi 2-test p = 0.003), there was no significant difference in the five-year overall survival (92% five-year survival without vs. 90% with adjuvant irradiation). In contrast statistical significant difference was found in recurrence-free interval between these groups (Wilcoxon test p = 0.02).
We have used 123I-labelled epidermal growth factor (EGF) scans to study 14 patients with advanced cervical cancer. Abnormal lymph node imaging was seen most clearly 6-8 h after the injection and revealed abnormal uptake by pelvic lymph nodes in 11 patients. 4 of these 11 had abnormal computerised tomographic and ultrasound scans; in the other 7 conventional radiology did not confirm the presence of disease.
Data are presented on 434 patients treated at the Gynecologic Radiotherapy Department of the University of Vienna for invasive primary carcinoma of the vagina between 1952 and 1984; data on 110 patients treated in the last few years are more detailed. In stage I, 5-year survival was 76.7%; in stage II, 44.5%; in stage III, 31%; and in stage IV, 18.2%. The overall uncorrected 5-year survival rate was 39.9%. The disease is primarily one of the elderly as 78% were found to be older than 60 years of age. Younger patients had a 5-year survival of 50%; patients between 61 and 75 years of age, 41.2%; and those 76 years of age or older, 34.3%. Patients with presenting symptoms had a cure rate of 36.9%, whereas 61.1% of asymptomatic cases survived. Best results (60%) were obtained when the lesion was in the upper third of the vagina; only 37% of patients with lesions of the middle third and lower third survived more than 5 years. Well-differentiated tumors were associated with a 5-year survival of 62.5%; and poorly differentiated tumors, with a rate of 34.9%. Our results indicate that stage of disease is the most significant prognostic factor, but age of the patient, location of lesion in the vagina, and differentiation of the tumor influence outcome too. The majority of patients were managed by a combination of external pelvic irradiation and local application of radium. In stage I and II patients treated with radium alone, good results were obtained, but no patient with stage III or IV disease survived 5 years when external irradiation was not performed.
Pulsed Doppler Flow Measurements in patients suffering from collum cancer using a coloured pulsed Doppler technique measurements of blood flow of the uterine artery were performed in a group of 35 patients suffering from an inoperable collum cancer (stage II and III according FIGO) and compared with a collective of 30 healthy women with normal anamnesis. The mean pulsatility index (PI) was significantly lower in the sick group (stage II 1.6 +/- 1.17, stage III 0.76 +/- 0.21) than in the healthy group (PI = 3.18 +/- 0.99) (p less than 0.01). In 14 subjects of the last group there was no significant difference in PI between the left and right uterine artery (left: PI 2.81 +/- 0.83), right: PI 2.78 +/- 0.76).
An analysis was made of the procedure when PAP IV occurs in pregnancy. 63 patients between 1. 1. 1985 and 1. 4. 1990 from 6 main hospitals in Vienna were included in this study. In 30 cases, a cone biopsy was made during pregnancy, whilst in 33 cases, the operation was performed after delivery. In both groups, the tissue showed in the histological examination nearly the same incidence rate of carcinoma stage Ia, carcinoma in situ as well as mild, moderately severe, and severe dysplasia. A significant frequency was found for a delivery before the 35th week of gestation, if conisation was done during pregnancy. An increased negative foetal outcome was also found if the operation was performed after the 16th week of gestation. Conservative procedure showed a better foetal outcome with the same security, in that carcinoma stage Ib was never overlooked. On-target biopsy under colposcopic control, combined with a conisation 8 to 10 weeks after delivery, is therefore recommended.
Endometrial carcinoma is the most common gynaecological invasive cancer. Since its incidence is increasing, more patients will develop recurrent disease. In an attempt to identify possible prognostic factors associated with survival, we reviewed the results of 45 patients treated in our department for recurrent clinical stage I endometrial carcinoma. All patients received primary therapy consisting of surgical resection. 16 patients developed recurrent disease after initial operative treatment and adjuvant radiotherapy. The minimum follow-up of 3 years was available in 43 patients and the actual 3-year survival rate was estimated 42% (median 16 months). Significant prognostic factors were recurrence site--vagina, 51% (17/33 pts) vs extravaginal, 20% (2/10 pts) (p = 0.01), and histological cell type--non-papillary carcinoma, 50% (17/34 pts) vs papillary adenocarcinoma, 22% (2/9 pts) (p = 0.02). Late recurrences have been reported to carry a better prognosis, than those that recur early. In the present study, time of onset did not appear to be a significant factor--recurrence occurs within 24 months, 36% (9/25 pts) vs recurrence appearing after 2 years, 55% (10/18 pts). We suggest, that systemic therapy should be prospectively evaluated in high-risk patients. Selected patients with recurrent disease--cases of non-papillary histological cell type and vaginal recurrence--can be cured by radiotherapy.
In a retrospective study of 208 surgically treated cases of endometrial cancer with pelvic lymphadenectomy, histomorphology with subtypes, tumour grading, infiltration of the myometrium, blood- and lymphatic vessel invasion and pelvic lymph node metastases, were analysed. Typical adenocarcinomas had lymph node involvement in 9% of the patients, whereas unfavourable subtypes showed in 27%. In patients with tumour grading I, the lymph nodes were involved in only 4.5% and with grading 3 in 31.4%, respectively. If the carcinoma was limited to the endometrium, no lymph node metastases could be detected. If the inner half of the myometrium was involved, pelvic nodes were positive in 9.2% with deeper infiltration in 27.3% of the cases. With obvious invasion of blood or lymph vessels, lymph nodes were positive in 43.2% of the cases. A simple score for these histopathological risk factors is proposed, enabling the allocation to patient groups of similar risk on the basis of a point system for individual prognostic factors. With a score of 1-2 points (13.5% of the cases) the prognosis is good and adjuvant irradiation does not seem necessary. With 3-4 points (34.1% of the cases), local vaginal irradiation is recommended. With 5 or more points, we recommended, in addition to vaginal irradiation, aggressive irradiation of the small pelvis, 52.4% were in this group, from which 85% were symptom-free at the critical 5 year point. In case of positive pelvic lymph node, 67% of the patients survived after adequate adjuvant follow-up irradiation.