Human papillomavirus (HPV) DNA has been regularly detected in primary cervical carcinomas and in some metastatic lesions. Using Southern blot hybridization on autopsy material we found HPV 16 DNA in a primary cervical carcinoma and in multiple metastases therefrom.

Objective: To create a strategy for sonographic differentiation of benign andMethods: Multiple sonomorphologic criteria were analyzed prospectively in 754 tumors. Four hundred were found in premenopausal and 354 in postmenopausal women. In a logistic regression model, relevant criteria were selected, and a diagnostic formula for tumor differentiation was derived.Results: There were 165 malignant tumors, of which 37 (9.2%) were found in premenopausal and 128 (36.2%) in postmenopausal women. In both groups, the criteria of solid phase and ascites were the most significant. Further important diagnostic criteria were structure and tumor size in premenopausal women and cyst architecture and tumor surface in postmenopausal women. These results allowed an estimation of the probability of malignancy. Using a cutoff point of 10% for the probability to classify tumors as malignant, the sensitivity and specificity in premenopausal patients were 86.5% and 92.6%, respectively, with an accuracy of 92%. In postmenopausal women, the sensitivity, specificity, and accuracy were 93%, 82.7%, and 86.6%, respectively. Assuming a prevalence as given in the study, the positive and negative predictive values were 54.4% and 98.5% in premenopausal and 75.3% and 95.4% in postmenopausal women.Conclusions: With four binary criteria, a useful diagnostic formula for tumor differentiation was obtained. However, estimates for sensitivity, specificity, and accuracy may be too optimistic because they were derived from the same data that were already used for model selection. Copyright (C) 1997 by The American College of Obstetricians and Gynecologists.

Abstract Several randomized studies in patients with advanced ovarian cancer have dealt with the comparison of cisplatin and carboplatin when given as either a single drug or in combination. The German Ovarian Cancer Study Group (GOCA) performed a prospective randomized trial in a subgroup of patients specified by a successful cytoreductive operation before the start of chemotherapy. From February 1987 to May 1990, 173 previously untreated patients with stage III and IV disease and limited tumor bulk of 2 plus carboplatin 350 mg/m 2 or cyclophosphamide 1000 mg/m 2 plus cisplatin 80 mg/m 2 . The drugs had to be administered on Day 1 every 28 days for six subsequent courses. Results. In 158 assessable patients no significant differences in pathologically confirmed CR rates (pCR: 14% vs 16%), median time to progression (PFI: 19 months vs 26 months), and overall survival (OS: 35 months vs 37 months) were observed. Refusal of therapy due to toxicity was more frequent in the cisplatin arm, whereas patients with progressive disease predominated in the carboplatin arm. Nonhematologic adverse effects were more likely to occur with cisplatin whereas carboplatin patients experienced more myelosuppression. As prognostic factors associated with an increased risk of progressive disease and shorter overall survival time, stage of disease and amount of residual tumor after first surgery were determined. Conclusions. Carboplatin proved to be effective in patients with optimally debulked ovarian cancer. However, neither regimen used in this trial is sufficiently active to prevent tumor progression in the majority of patients.

The 5-year survival of patients with advanced cervical cancer is poor. Major problems are the high frequency of pelvic recurrences and distant metastases. To prevent both, various efforts have been made to combine local radiotherapy with systemic chemotherapy. In this prospective study, 28 previously untreated patients with advanced cervical cancer (FIGO IIB-IVB) were treated with a newly designed therapy consisting of fractionated external beam irradiation (54 Gy) followed by two intracavitary cesium (Cs) applications (2 × 15 Gy), combined with carboplatin (70 mg m-2), 5-fluorouracil (5-FU) (400 mg m-2) and folinic acid(400 mg m-2). Cytotoxic agents were given intravenously on days 1, 8, 15, 22 and 29 as 1-day courses during external irradiation followed by three 3-day courses with carboplatin (100 mg m-2 i.v. daily), 5-FU(400 mg m-2 i.v. daily) and folinic acid (400 mg m-2i.v. daily) after 8, 12 and 16 weeks of treatment. Acute toxicities (≥ WHO grade 2) were leucopenia (27 of 28 patients), diarrhea (23/28), abdominal pain (19/28), nausea (14/28) and skin desquamation (12/28). Clinically diagnosed pelvic response was achieved in 88.5% (23/26) with a complete response of 34.5% (9/26). As yet, 19 of 26 patients (73.1%) are alive and well (persistent complete/partial remission), two patients (7.7%) are alive with local progression, four (15.4%) have died from pelvic and/or distal recurrence and one (3.8%) died some weeks after the start of therapy. The combined modality treatment concept has to be considered for the therapy of advanced cervical cancer and a prospective and randomized trial with a greater number of patients is warranted.

In a retrospective study the prognostic significance of nuclear DNA content was investigated, as measured by flow cytometry, of the tumor specimens from 212 women with nonpretreated FIGO stage IB and II cervical cancer. One-hundred and thirty cases (62%) were found to be diploid, whereas 82 (38%) were aneuploid. Univariate analysis of the follow-up data showed an increased relative risk (RR) for recurrence free survival (RFS) for stage II tumors (RR = 1.87, 95%CI: 1.13-3.10, P = 0.015) and for age (RR = 1.52, 95%CI: 0.66-3.52 and RR = 2.35, 95%CI: 1.19-4.65, P = 0.032). Ploidy showed a relative risk of 1.33 (95%CI: 0.83-2.13, NS). In addition, univariate analysis of overall survival (OS) revealed similar results. For the subgroup of patients with primary surgery (n = 151), positive pelvic nodes (RR = 5.38, 95%CI: 2.70-10.71, P = 0.0001) and parametrial extension (RR = 2.53, 95%CI: 1.24-5.17, P= 0.011) were significant factors for OS after univariate analysis, the estimated effects on RFS were slightly smaller. Multivariate analysis of RFS for the whole study population showed age, histologic grade and stage with a slightly increased risk, but no effect was significant. Ploidy with an RR of 0.97 (95%CI: 0.58-1.62) seems to have no influence on prognosis. For the subgroup with primary surgery, ploidy again failed statistical significance with an RR of 1.20 (95%CI: 0.58-2.49). Our results suggest that abnormalities of the nuclear DNA content in this homogeneous group of patients are associated with clinical and morphological prognosticators, however, ploidy is not an independent prognostic factor for RFS, or for the whole study population or for the subgroup with primary surgery.

Splice variants of the cell surface glycoprotein CD44 (CD44v) have been implicated in the progression of various human tumors. In the present study, we have examined the expression pattern of a CD44v epitope encoded by the adjacent variant exons v7 and v8 during human cervical carcinogenesis, While only I/II normal cervical squamous epithelia was positive for this epitope by immunohistochemistry, 4/21 samples of low-grade squamous intra-epithelial lesions (LSIL), 17/35 samples of high-grade squamous intra-epithelial lesions (HSIL), 11/12 samples of the HSIL subgroup of carcinoma in site and 17/17 cases of invasive cervical carcinoma showed CD44v7/8 epitope expression. In addition to CD44 variant expression, we have analyzed 67 lesions for the presence of HPV16/18-DNA using PCR. Most of the samples expressing the v7/8 epitope were also HPV16-positive (29/32), whereas only 17/35 of the v7/8-negative samples were HPV16-positive. HPV18 DNA was found in only one invasive carcinoma, Our data suggest that high-risk HPV infection may precede CD44v7/8 expression and that the number of samples expressing the CD44 v7/8 epitope increases during carcinogenesis and reaches nearly 100% at the carcinoma in situ stage. This CD44 epitope could, therefore, serve as a diagnostic marker of cervical squamous cell carcinomas and as a possible target for CD44v7/8 epitope-directed therapies. (C) 1996 Wiley-Liss, Inc.

Transvaginal sonomorphologie and colour Doppler measurements were obtained preoperatively in 212 adnexal tumours: 81 premenopausal tumours (13 malignant and 68 benign) and 131 postmenopausal tumours (55 vs 76). Tumours were divided into five different scores according to their sonomorphology [16]. Scores I and II are related to benign tumours. Score V represents typically malignant tumours. Scores III and IV are associated with benign and malignant tumours. If score I and II are considered as benign and score III to V as malignant the sensitivity in pre- and postmenopausal tumours is 90%. However, the specificity is only 56% vs 70% respectively. In order to improve the accuracy, colour Doppler was additionally performed in tumours with sonomorphological score III and IV. The following criteria were tested: minimum resistance index (Rlmin), number of tumour arteries (ART), maximum (Smax) and sum (Ssum) of peak systolic velocities. All criteria showed significant differences between benign and malignant tumours. Tumours of score III and IV were differentiated by colour Doppler with an accuracy between 66% and 81% for premenopausal and 69% to 86% for postmenopausal women. The combination of sonomorphology and colour Doppler increased the accuracy between 84% and 90% with a sensitivity of up to 92% in pre- and 89% in postmenopausal patients. Sequential colour Doppler sonography as a supplement to transvaginal sonography improves tumour differentiation. The limitation of colour Doppler measurements to score III and IV lesions reduced the length of examination time to a reasonable extent.

PURPOSE:The medical management of women with cervical carcinoma would benefit from a test that might predict which patients have a high risk of progression or recurrence. The detection of micrometastases in regional lymph nodes may be such a test. At least 90% of cervical carcinomas worldwide contain human papillomavirus (HPV) DNA. In a pilot study, we evaluated a polymerase chain reaction-based method for the detection of human papillomavirus DNA in archival routine sections of regional lymph nodes as a marker of micrometastasis in patients with a long-term follow-up period.PATIENTS AND METHODS:We analyzed 134 archival routine slides of histologically tumor-free lymph nodes derived from 21 patients with clinically and pathologically determined stage Ib, IIa, and IIb HPV-16 positive cervical carcinoma. The patients had been selected for good (still alive with a follow-up time of at least 5 years) or fatal outcome (dead of disease within 3 years). The amount of HPV-16 DNA was estimated by comparison with standards.RESULTS:All patients without strongly HPV-positive lymph nodes survived. In contrast, 8 of 12 women with strongly HPV-positive lymph nodes died of cervical carcinoma.CONCLUSIONS:In patients with cervical cancer, an approach based on a PCR test for HPV DNA in tumor-free regional lymph nodes may allow early identification of women at high risk for relapse who should receive adjuvant treatment.

Transvaginal sonomorphologie and colour Doppler measurements were obtained preoperatively in 212 adnexal tumours: 81 premenopausal tumours (13 malignant and 68 benign) and 131 postmenopausal tumours (55 vs 76). Tumours were divided into five different scores according to their sonomorphology [16]. Scores I and II are related to benign tumours. Score V represents typically malignant tumours. Scores III and IV are associated with benign and malignant tumours. If score I and II are considered as benign and score III to V as malignant the sensitivity in pre- and postmenopausal tumours is 90%. However, the specificity is only 56% vs 70% respectively. In order to improve the accuracy, colour Doppler was additionally performed in tumours with sonomorphological score III and IV. The following criteria were tested: minimum resistance index (Rlmin), number of tumour arteries (ART), maximum (Smax) and sum (Ssum) of peak systolic velocities. All criteria showed significant differences between benign and malignant tumours. Tumours of score III and IV were differentiated by colour Doppler with an accuracy between 66% and 81% for premenopausal and 69% to 86% for postmenopausal women. The combination of sonomorphology and colour Doppler increased the accuracy between 84% and 90% with a sensitivity of up to 92% in pre- and 89% in postmenopausal patients. Sequential colour Doppler sonography as a supplement to transvaginal sonography improves tumour differentiation. The limitation of colour Doppler measurements to score III and IV lesions reduced the length of examination time to a reasonable extent.

Color Doppler allows flow detection in small tumor vessels. Due to the vascularity associated with the growth of malignancies, this method can be used to differentiate between benign and malignant breast lesions. In order to study the typical flow characteristics, we investigated multiple Doppler flow parameters. A UM9 HDI (ATL) was used with a linear transducer L 10‐5. The number of tumor vessels and the mean, maximum and total flow velocity were measured in 325 benign and 133 malignant lesions and showed highly significant differences ( p < 0.0001). Flow profiles (resistance index and systolic/diastolic frequency ratio) showed a large overlap and did not allow accurate tumor differentiation when mean and minimum values were analyzed. Surprisingly, the maximum resistance index and systolic/diastolic frequency ratio were significantly higher in carcinomas than in benign lesions, but the overlap of the values was wider than the flow velocity measurements. Using the vessel number and the total tumor vascularity, 90% of all lesions could be differentiated. A difficulty that we encountered was that a few cancers have very low flow values and some of the proliferative benign lesions can have increased flow. Copyright © 1995 International Society of Ultrasound in Obstetrics and Gynecology

OBJECTIVE:To help clarify the possible usefulness of nuclear DNA content and S-phase fraction (SPF) as additional prognostic factors in node-positive breast cancer patients because there is increased interest in the development of new factors that might provide more detailed prognostic information.STUDY DESIGN:We performed a DNA and SPF analysis by flow cytometry using a multivariate statistical model on a group of 139 node-positive breast cancer patients with clearly defined inclusion and exclusion criteria.RESULTS:The percentage of aneuploidy increased with the number of involved nodes. Aneuploid tumors were more often found among grade 3 and among receptor-negative tumors. Univariate analysis showed a strong effect on recurrence-free survival (RFS) for the number of involved nodes (P < .001) and for tumor size (P = .013). Grade 3 and receptor-negative tumors showed a nonsignificant trend toward increased risk. The relative risk of aneuploid tumors was 1.19 (95% confidence interval, 0.75-1.87). Multivariate analysis revealed only the number of involved nodes to be an independent prognostic factor (P = .002); ploidy showed no effect (P = .684). SPF did not show any significant effect on RFS, even in a univariate analysis.CONCLUSION:These results suggest that nuclear DNA content and SPF correlate with morphologic factors. Their routine clinical use, however, in node-positive breast cancer patients receiving adjuvant therapy seems to have no clinical relevance and therefore can be omitted.