Unilocular adnexal cysts with papillary projections but no other solid components: is there a diagnostic method that can classify them reliably as benign or malignant before surgery?

OBJECTIVES: To develop a logistic regression model for discrimination between benign and malignant unilocular solid cysts with papillary projections but no other solid components, and to compare its diagnostic performance with that of subjective evaluation of ultrasound findings (subjective assessment), CA 125 and the risk of malignancy index (RMI). METHODS: Among the 3511 adnexal masses in the International Ovarian Tumor Analysis (IOTA) database there were 252 (7%) unilocular solid cysts with papillary projections but no other solid components ('unilocular cysts with papillations'). All had been examined with transvaginal ultrasound using the IOTA standardized research protocol. The ultrasound examiner had also classified each mass as certainly or probably benign, unclassifiable, or certainly or probably malignant. A logistic regression model to discriminate between benignity and malignancy was developed for all unilocular cysts with papillations (175 tumors in the training set and 77 in the test set) and for unilocular cysts with papillations for which the ultrasound examiner was not certain about benignity/malignancy (113 tumors in the training set and 53 in the test set). The gold standard was the histological diagnosis of the surgically removed adnexal mass. RESULTS: A model containing six variables was developed for all unilocular cysts with papillations. The model had an area under the receiver-operating characteristics curve (AUC) on the test set of 0.83 (95% CI, 0.74-0.93). The optimal risk cut-off, as defined on the training set (0.35), resulted in sensitivity 69% (20/29), specificity 79% (38/48), positive likelihood ratio (LR +) 3.31 and negative likelihood ratio (LR-) 0.39 on the test set. The corresponding values for subjective assessment when using the ultrasound examiner's dichotomous classification of the mass as benign or malignant were 97% (28/29), 79% (38/48), 4.63 and 0.04. A model containing four variables was developed for unilocular cysts with papillations for which the ultrasound examiner was not certain about benignity/malignancy. The model had an AUC of 0.74 (95% CI, 0.60-0.88) on the test set. The optimal risk cut-off of the model, as defined on the training set (0.30), resulted in sensitivity 57% (12/21), specificity 78% (25/32), LR + 2.61 and LR- 0.55 on the test set. The corresponding values for subjective assessment were 95% (20/21), 78% (25/32), 4.35 and 0.06. CA 125 and RMI had virtually no diagnostic ability. CONCLUSIONS: Even though logistic regression models to predict malignancy in unilocular cysts with papillations can be developed, they have at most moderate performance and are not superior to subjective assessment for discrimination between benignity and malignancy.

Lesion size affects diagnostic performance of IOTA logistic regression models, IOTA simple rules and risk of malignancy index in discriminating between benign and malignant adnexal masses.

OBJECTIVES: To estimate the ability to discriminate between benign and malignant adnexal masses of different size using: subjective assessment, two International Ovarian Tumor Analysis (IOTA) logistic regression models (LR1 and LR2), the IOTA simple rules and the risk of malignancy index (RMI). METHODS: We used a multicenter IOTA database of 2445 patients with at least one adnexal mass, i.e. the database previously used to prospectively validate the diagnostic performance of LR1 and LR2. The masses were categorized into three subgroups according to their largest diameter: small tumors (diameter < 4 cm; n = 396), medium-sized tumors (diameter, 4-9.9 cm; n = 1457) and large tumors (diameter ≥ 10 cm, n = 592). Subjective assessment, LR1 and LR2, IOTA simple rules and the RMI were applied to each of the three groups. Sensitivity, specificity, positive and negative likelihood ratio (LR+, LR-), diagnostic odds ratio (DOR) and area under the receiver-operating characteristics curve (AUC) were used to describe diagnostic performance. A moving window technique was applied to estimate the effect of tumor size as a continuous variable on the AUC. The reference standard was the histological diagnosis of the surgically removed adnexal mass. RESULTS: The frequency of invasive malignancy was 10% in small tumors, 19% in medium-sized tumors and 40% in large tumors; 11% of the large tumors were borderline tumors vs 3% and 4%, respectively, of the small and medium-sized tumors. The type of benign histology also differed among the three subgroups. For all methods, sensitivity with regard to malignancy was lowest in small tumors (56-84% vs 67-93% in medium-sized tumors and 74-95% in large tumors) while specificity was lowest in large tumors (60-87%vs 83-95% in medium-sized tumors and 83-96% in small tumors ). The DOR and the AUC value were highest in medium-sized tumors and the AUC was largest in tumors with a largest diameter of 7-11 cm. CONCLUSION: Tumor size affects the performance of subjective assessment, LR1 and LR2, the IOTA simple rules and the RMI in discriminating correctly between benign and malignant adnexal masses. The likely explanation, at least in part, is the difference in histology among tumors of different size.

Clinically oriented three-step strategy for assessment of adnexal pathology.

OBJECTIVE: To determine the diagnostic performance of ultrasound-based simple rules, risk of malignancy index (RMI), two logistic regression models (LR1 and LR2) and real-time subjective assessment by experienced ultrasound examiners following the exclusion of masses likely to be judged as easy and 'instant' to diagnose by an ultrasound examiner, and to develop a new strategy for the assessment of adnexal pathology based on this. METHODS: 3511 patients with at least one persistent adnexal mass preoperatively underwent transvaginal ultrasonography to assess tumor morphology and vascularity. They were included in two consecutive prospective studies by the International Ovarian Tumor Analysis (IOTA) group: Phase 1 (1999-2005), development of the simple rules and logistic regression models LR1 and LR2, and Phase 2, a validation study (2005-2007). RESULTS: Almost half of the cases (43%) were identified as 'instant' to diagnose on the basis of descriptors applied to the database. To assess diagnostic performance in the more difficult 'non-instant' masses, we used only Phase 2 data (n = 1036). The sensitivity of LR2 was 88%, of RMI it was 41% and of subjective assessment it was 87%. The specificity of LR2 was 67%, of RMI it was 90% and of subjective assessment it was 86%. The simple rules yielded a conclusive result in almost 2/3 of the masses, where they resulted in sensitivity and specificity similar to those of real-time subjective assessment by experienced ultrasound examiners: sensitivity 89 vs 89% (P = 0.76), specificity 91 vs 91% (P = 0.65). When a three-step strategy was applied with easy 'instant' diagnoses as Step 1, simple rules where conclusive as Step 2 and subjective assessment by an experienced ultrasound examiner in the remaining masses as Step 3, we obtained a sensitivity of 92% and specificity of 92% compared with sensitivity 90% (P = 0.03) and specificity 93% (P = 0.44) when using real-time subjective assessment by experts in all tumors. CONCLUSION: A diagnostic strategy using simple descriptors and ultrasound rules when applied to the variables contained in the IOTA database obtains results that are at least as good as those obtained by subjective assessment of a mass by an expert.

Imaging in gynecological disease (7): clinical and ultrasound features of Brenner tumors of the ovary.

OBJECTIVES: To describe clinical and ultrasound features of Brenner tumors of the ovary. METHODS: In this retrospective study, the databases of the International Ovarian Tumor Analysis (IOTA) studies and one tertiary center were searched to identify patients who had undergone an ultrasound scan before surgery for an adnexal mass that proved to be a Brenner tumor. Twenty-eight patients with 29 Brenner tumors were included, most of which had been collected within the framework of the IOTA studies. An experienced ultrasound examiner reviewed available ultrasound images (available for 14 tumors), searching for a pattern specific to Brenner tumors. RESULTS: Most patients were postmenopausal and asymptomatic. Twenty-four (83%) tumors were benign, two (7%) were borderline and three (10%) were malignant. Most benign tumors (17/24, 71%) contained solid components and manifested no or minimal blood flow on Doppler examination (19/24, 79%). Information about calcifications was available for 15 benign tumors, and in 13 (87%) calcifications were present. The five borderline and invasively malignant tumors contained solid components less often than did the benign ones (3/5, 60%) and were more richly vascularized on Doppler examination. Information about calcifications was available for four borderline or invasively malignant tumors, and in three (75%) calcifications were present. CONCLUSION: We failed to demonstrate ultrasound features specific to Brenner tumors. A prospective study is needed to determine if ultrasound features of calcifications can discriminate between Brenner tumors and other types of ovarian tumor.

Adnexal masses difficult to classify as benign or malignant using subjective assessment of gray-scale and Doppler ultrasound findings: logistic regression models do not help.

OBJECTIVE: To develop a logistic regression model that can discriminate between benign and malignant adnexal masses perceived to be difficult to classify by subjective evaluation of gray-scale and Doppler ultrasound findings (subjective assessment) and to compare its diagnostic performance with that of subjective assessment, serum CA 125 and the risk of malignancy index (RMI). METHODS: We used data from the 3511 patients with an adnexal mass included in the International Ovarian Tumor Analysis (IOTA) studies. All patients had been examined using transvaginal gray-scale and Doppler ultrasound following a standardized research protocol carried out by an experienced ultrasound examiner using a high-end ultrasound system. In addition to prospectively collecting information on > 40 clinical and ultrasound variables, the ultrasound examiner classified each mass as certainly or probably benign, unclassifiable, or certainly or probably malignant. A logistic regression model to discriminate between benignity and malignancy was developed for the unclassifiable masses (n = 244, i.e. 7% of all tumors) using a training set (160 tumors, 45 malignancies) and then tested on a test set (84 tumors, 28 malignancies). The gold standard was the histological diagnosis of the surgically removed adnexal mass. The area under the receiver-operating characteristics curve (AUC), sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were used to describe diagnostic performance and were compared between subjective assessment, CA 125, the RMI and the logistic regression model created. RESULTS: One variable was retained in the logistic regression model: the largest diameter (in mm) of the largest solid component of the tumor (odds ratio (OR) = 1.04; 95% CI, 1.02-1.06). The model had an AUC of 0.68 (95% CI, 0.59-0.78) on the training set and an AUC of 0.65 (95% CI, 0.53-0.78) on the test set. On the test set, a cut-off of 25% probability of malignancy (corresponding to the largest diameter of the largest solid component of 23 mm) resulted in a sensitivity of 64% (18/28), a specificity of 55% (31/56), an LR+ of 1.44 and an LR- of 0.65. The corresponding values for subjective assessment were 68% (19/28), 59% (33/56), 1.65 and 0.55. On the test set of patients with available CA 125 results, the LR+ and LR- of the logistic regression model (cut-off = 25% probability of malignancy) were 1.29 and 0.73, of subjective assessment were 1.45 and 0.63, of CA 125 (cut-off = 35 U/mL) were 1.24 and 0.84 and of RMI (cut-off = 200) were 1.21 and 0.92. CONCLUSIONS: About 7% of adnexal masses that are considered appropriate for surgical removal cannot be classified as benign or malignant by experienced ultrasound examiners using subjective assessment. Logistic regression models to estimate the risk of malignancy, CA 125 measurements and the RMI are not helpful in these masses.

Endometriomas: their ultrasound characteristics.

OBJECTIVES: To describe the ultrasound characteristics of endometriomas in pre- and postmenopausal patients and to develop rules that characterize endometriomas. METHODS: All patients included in the International Ovarian Tumor Analysis (IOTA) studies were used in our analysis. Patients with an adnexal mass were scanned by experienced sonologists using a standardized research protocol. The gold standard was the histology of the surgically removed adnexal mass. The gray-scale and Doppler ultrasound characteristics of the endometriomas were compared with those of other benign and malignant masses. Based on decision-tree analysis, the existing literature and clinical experience, ultrasound rules for the detection of endometriomas were created and evaluated. RESULTS: Of all 3511 patients included in the IOTA studies, 713 (20%) had endometriomas. Fifty-one per cent of the endometriomas were unilocular cysts with ground glass echogenicity of the cyst fluid. These characteristics were found less often among other benign tumors or malignancies, or among the small set of endometriomas (4%) that were found in postmenopausal patients. Based on the decision-tree analysis, the optimal rule to detect endometriomas was 'an adnexal mass in a premenopausal patient with ground glass echogenicity of the cyst fluid, one to four locules and no papillations with detectable blood flow'. Based on clinical considerations, the following rule: 'premenopausal status, ground glass echogenicity of the cyst fluid, one to four locules and no solid parts' seems preferable. CONCLUSIONS: Several rules had a good ability to characterize endometriomas. The ultrasound characteristics of endometriomas differ between pre- and postmenopausal patients. Masses in postmenopausal women whose cystic contents have a ground glass appearance have a high risk of malignancy.

Ovarian cancer prediction in adnexal masses using ultrasound-based logistic regression models: a temporal and external validation study by the IOTA group.

OBJECTIVES: The aims of the study were to temporally and externally validate the diagnostic performance of two logistic regression models containing clinical and ultrasound variables in order to estimate the risk of malignancy in adnexal masses, and to compare the results with the subjective interpretation of ultrasound findings carried out by an experienced ultrasound examiner ('subjective assessment'). METHODS: Patients with adnexal masses, who were put forward by the 19 centers participating in the study, underwent a standardized transvaginal ultrasound examination by a gynecologist or a radiologist specialized in ultrasonography. The examiner prospectively collected information on clinical and ultrasound variables, and classified each mass as benign or malignant on the basis of subjective evaluation of ultrasound findings. The gold standard was the histology of the mass with local clinicians deciding whether to operate on the basis of ultrasound results and the clinical picture. The models' ability to discriminate between malignant and benign masses was assessed, together with the accuracy of the risk estimates. RESULTS: Of the 1938 patients included in the study, 1396 had benign, 373 had primary invasive, 111 had borderline malignant and 58 had metastatic tumors. On external validation (997 patients from 12 centers), the area under the receiver-operating characteristics curve (AUC) for a model containing 12 predictors (LR1) was 0.956, for a reduced model with six predictors (LR2) was 0.949 and for subjective assessment was 0.949. Subjective assessment gave a positive likelihood ratio of 11.0 and a negative likelihood ratio of 0.14. The corresponding likelihood ratios for a previously derived probability threshold (0.1) were 6.84 and 0.09 for LR1, and 6.36 and 0.10 for LR2. On temporal validation (941 patients from seven centers), the AUCs were 0.945 (LR1), 0.918 (LR2) and 0.959 (subjective assessment). CONCLUSIONS: Both models provide excellent discrimination between benign and malignant masses. Because the models provide an objective and reasonably accurate risk estimation, they may improve the management of women with suspected ovarian pathology.

Phase II of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer, previously treated with platinum and taxanes.

BACKGROUND: A prospective phase II study was conducted to evaluate the efficacy and toxicity of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer. PATIENTS AND METHODS: Patients had a maximum of three prior chemotherapy lines with no more than two prior platinum-containing regimens and a progression-free interval after the last dose of platinum <12 months. A total dose of 4 mg/m(2)/cycle (0.8 mg/m(2)/day from day 1 to day 5) was administered, repeated every 28 days. RESULTS: From June 2005 to December 2005, 69 assessable patients were enrolled. The best overall response to study treatment by combined CA-125 and RECIST criteria was partial response in 17 patients (24.6%) and disease stabilization in 22 patients (31.9%). The median time to progression and overall survival were 3.8 and 16.2 months, respectively. A total of 312 cycles were administered. Neutropenia grade 4 and thrombocytopenia grade 4 occurred in 17.4% and 7.2% of patients, respectively. Diarrhea grade 4 was never observed. Asthenia and fatigue were reported by 36.2% and 18.8% of patients, but were all grade 2 or less. CONCLUSION: Gimatecan is a new active agent in previously treated ovarian cancer with myelosuppression as main toxicity.

Diagnostic accuracy of transvaginal ultrasound examination for assigning a specific diagnosis to adnexal masses.

OBJECTIVES: To determine the sensitivity and specificity of subjective evaluation of gray-scale and Doppler ultrasound findings (here called pattern recognition) when used by experienced ultrasound examiners with regard to making a specific diagnosis of adnexal masses. METHODS: Within the framework of a European multicenter study, the International Ovarian Tumor Analysis study, comprising nine ultrasound centers, women with at least one adnexal mass were examined with gray-scale and color Doppler ultrasonography by experienced ultrasound examiners. A standardized examination technique, and standardized terms and definitions were used. Using pattern recognition the examiners classified each mass as benign or malignant and suggested a specific diagnosis (e.g. dermoid cyst or endometrioma). The reference standard was the histology of the surgically removed adnexal tumors. RESULTS: A total of 1066 women were included, of whom 800 had a benign mass and 266 a malignant mass. A specific diagnosis based on ultrasound findings was suggested in 899 (84%) tumors. The specificity was high for all diagnoses (range, 94-100%). The sensitivity was highest for benign teratoma/dermoid cysts (86%, 100/116), hydrosalpinges (86%, 18/21), peritoneal pseudocysts (80%, 4/5) and endometriomas (77%, 153/199), and lowest for functional cysts (17%, 4/24), paraovarian/parasalpingeal cysts (14%, 3/21), benign rare tumors (11%, 1/9), adenofibromas (8%, 3/39), simple cysts (6%, 1/18) and struma ovarii (0%, 0/5). The positive and negative likelihood ratios of pattern recognition with regard to dermoid cysts, hydrosalpinges and endometriomas were 68.2 and 0.14, 38.9 and 0.15, and 33.3 and 0.24, respectively. Dermoid cysts, hydrosalpinges, functional cysts, paraovarian cysts, peritoneal pseudocysts, fibromas/fibrothecomas and simple cysts were never misdiagnosed as malignancies by the ultrasound examiner, whereas more than 10% of inflammatory processes, adenofibromas and rare benign tumors including struma ovarii were misdiagnosed as malignancies. CONCLUSIONS: Using subjective evaluation of gray-scale and Doppler ultrasound findings it is possible to make an almost conclusive diagnosis of a dermoid cyst, endometrioma and hydrosalpinx. Many other adnexal pathologies can be recognized but not confidently confirmed or excluded.

A phase II, randomized trial of neo-adjuvant chemotherapy comparing a three-drug combination of paclitaxel, ifosfamide, and cisplatin (TIP) versus paclitaxel and cisplatin (TP) followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the Snap-02 Italian Collaborative Study.

BACKGROUND: The efficacy and tolerability of the regimen containing paclitaxel and cisplatin (TP) in the neo-adjuvant treatment of locally advanced squamous cell cervical cancer are unknown. The TIP regimen (TP plus ifosfamide) showed high efficacy but high toxicity and it is used as an internal control. PATIENTS AND METHODS: In all, 154 patients were randomized to TP (paclitaxel 175 mg/m(2) + cisplatin 75 mg/m(2); n = 80) or TIP (TP + ifosfamide 5 g/m(2); n = 74), three cycles, followed by radical surgery. Pathological response to chemotherapy was classified as optimal [no residual tumor (complete response) or residual disease with < or = 3 mm stromal invasion (PR1)] or suboptimal response. RESULTS: Patient characteristics (TP/TIP): stage IB2 (56%/64%), IIA (18%/14%), IIB (20%/19%), III-IVA (5%/4%) and median age (42 years/45 years). The optimal response rate in the TP group was 25%, 95% confidence interval (CI) = 16% to 37% and 43%, 95% CI = 31% to 55% in the TIP group. Grades 3-4 leukopenia (6%/53%) and neutropenia (26%/76%) were significantly more frequent on TIP. CONCLUSION: TP performance was below expectation since the lower 95% confidence limit of the optimal response rate failed to reach the prespecified minimum requirement of efficacy, i.e. 22%. The TIP regimen confirmed its activity but was associated with higher haematological toxicity than TP.

A phase II randomised clinical trial comparing cisplatin, paclitaxel and ifosfamide with cisplatin, paclitaxel and epirubicin in newly diagnosed advanced epithelial ovarian cancer: long-term survival analysis.

To test the feasibility and efficacy of epirubicin and ifosfamide added to first-line chemotherapy with cisplatin and paclitaxel in a phase II randomised clinical trial. Patients with histologically proven epithelial ovarian cancer were randomly assigned to receive first-line polychemotherapy with cisplatin/paclitaxel/epirubicin (CEP) or cisplatin/paclitaxel/ifosfamide (CIP) for six cycles every 21 days. Two hundred and eight patients were randomised between the two treatment arms and the median number of cycles per patient was six. Toxicity was predominantly haematological with both regimens; however, anaemia, leucopaenia, neutropaenic fever and use of granulocyte colony-stimulating factors and transfusion were significantly more frequent in the CIP treatment arm. Response rates were 85% (95% confidence interval (CI) 77-93%) in the CIP arm and 90% (95% CI 84-96%) in the CEP arm; complete response rates were 48 and 52%. After a median follow-up of 82 months, median overall survival (OS) was 51 and 65 months; 5-year survival rates were respectively 43 and 50%. In this clinical trial, both regimens showed good efficacy, but toxicity was heavier with the CIP regimen. Considering that more than 50% of patients were suboptimally debulked after the first surgery, OS seems to be longer than is commonly reported. This unexpected finding might be a consequence of the close surgical surveillance and aggressive chemotherapeutic approach.

DeltaNp63 expression is associated with poor survival in ovarian cancer.

BACKGROUND: P63 belongs to the 'p53 family' whose role in cancer progression has been recently revisited in light of the plethora of splicing variants that are generated. We analyzed the expression of the full-length TAp63 gene and its dominant-negative form deltaNp63 in ovarian cancer biopsies to correlate their expression with clinical outcome. MATERIALS AND METHODS: Real-time RT-PCR analysis was used to determine the levels of TAp63 and deltaNp63 in 83 stage I and in 86 stage III ovarian cancer biopsies and in seven human ovarian cancer cell. RESULTS: TAp63 levels were comparable in stage I and stage III, but deltaNp63 levels increased 77-fold in stage III, independently of the p53 status. Patients with high deltaNp63 expression had the worst overall survival (OS); patients with a deltaNp63/TAp63 ratio >2 had a poor OS. Patients with a high deltaNp63/TAp63 ratio were those with a poor response to platinum-based therapy. CONCLUSIONS: Data indicate a role for deltaNp63 as a potential biomarker to predict patient's outcome and tumor progression in ovarian cancer. This would have particularly clinical relevance in ovarian cancer where the high rate of mortality reflects our lack of knowledge of molecular mechanisms underlying cell progression toward malignancy.

A phase II clinical trial of topotecan and carboplatin in patients with newly diagnosed advanced epithelial ovarian cancer.

A phase II clinical trial conducted to evaluate the efficacy and tolerability of topotecan and carboplatin as first-line therapy for women with advanced epithelial ovarian cancer was the objective of this study. Patients had histologically confirmed ovarian epithelial cancer with at least one measurable lesion. Patients received topotecan 1.5 mg/m(2) on days 1-3 and carboplatin at an area under the curve (AUC) of 5 on day 3 every 21 days for six cycles. All 42 patients enrolled were evaluable for response and toxicity. Median number of cycles delivered was six. Overall response rate was 71%, with 19 clinical complete responses (45%) and 11 clinical partial responses (26%). Median survival time was 47 months and 5-year survival was 42%. Myelosuppression was the predominant toxicity, with grade 3 or 4 neutropenia occurring in 100% of patients. However, this toxicity was transient and easily manageable; no patients experienced febrile neutropenia. The combination of topotecan and carboplatin is active in advanced epithelial ovarian cancer. Delay of therapy by 1 week or topotecan dose reduction to 1.25 mg/m(2) is the first-choice option to reduce topotecan toxicity without affecting the efficacy. Moreover, a chemotherapy regimen using weekly topotecan, which is currently being tested, should be considered.

Primary malignant vaginal melanoma treated with adriamycin and ifosfamide: a case report and literature review.

BACKGROUND: Vaginal melanoma is a very rare but highly malignant gynecological disease, usually diagnosed in postmenopausal woman. The prognosis tends to be poor and it is associated with high rate of recurrence and short survival rates. CASE: The following paper describes a case report regarding a 72-year-old woman with a locally advanced malignant melanoma. The previous erroneous histopathological diagnosis was leiomyosarcoma. She underwent chemotherapy with 3 courses of doxorubicin and ifosfamide. The diagnosis of malignant melanoma was obtained after a repeated biopsy and further pathological investigations. She later underwent radical surgery and 2 additional cycles of the same chemotherapy. At present, 7 months after the last cycle, the patient was locally disease-free, but developed brain metastases, requiring chemotherapy treatment. CONCLUSION: In view of poor survival, this chemotherapy regimen may be an interesting alternative to the traditional treatment of vaginal melanoma.

Ifosfamide in the treatment of malignant epithelial ovarian tumors.

Ifosfamide is one of the best-known alkylating agents. In advanced epithelial ovarian cancer, it has been tested in association with cisplatin, achieving results equal, if not better than cyclophosphamide, with acceptable toxicity. In second-line therapy, it shows remarkable activity, even in patients refractory to cisplatin already treated with cyclophosphamide, with more severe, but always manageable toxicity. In gynecological sarcomas, ifosfamide is, together with doxorubicin, the reference drug for chemotherapy.

Cell cycle-related phosphatases CDC25A and B expression correlates with survival in ovarian cancer patients.

Alterations in cell cycle regulating proteins are common in many cancer types. Recent data suggest a possible link between CDC25 phosphatases overexpression and malignancy. Our objective was to evaluate the expression of the three cell cycle-related phosphatases CDC25A, CDC25B and CDC25C in patients with ovarian cancer. All the patients had a minimal follow up of three years. CDC25A, CDC25B and CDC25C expression were investigated by immunohistochemistry in 106 patients with ovarian cancer. CDC25A and CDC25B were found expressed in almost all the samples analyzed, while CDC25C was undetectable in more than 80% of the patients. The low evaluable data on CDC25C expression, did not allow any association between the expression of this phosphatase and prognosis. The expression of CDC25A and CDC25B showed some evidences of association with a poor prognosis (p = 0.034 and p = 0.058 respectively). This relationship was independent of other factors such as tumor grade, histotype, stage and residual tumor after surgery. In the same patients the examined parameters (residual tumor, grade, stage and histotype) did show the expected relation with survival. The results indicate that high CDC25A and CDC25B expression is related to a worse prognosis in ovarian cancer patients. CDC25 phosphatases expression can be regarded as a possible prognostic factor for ovarian cancer and these proteins should be evaluated as potential molecular targets of novel drugs against this human neoplasm.

Transvaginal ultrasonographic characterization of ovarian masses: comparison of five scoring systems in a multicenter study.

The aim of this work was to test and compare the accuracy of five different morphological scoring systems to identify malignant ovarian masses in a prospective multicenter study. Four of the systems had previously been reported by Granberg, Sassone, De Priest and Lerner and the fifth is newly developed. A total of 330 ovarian neoplasms were collected in three different centers, which adopted the same diagnostic procedures. Of these, 261 masses were benign (mean diameter 50 +/- 26 mm) and 69 were malignant (mean diameter 69 +/- 33 mm) (prevalence 21%). The area under the receiver operating characteristic (ROC) curve for the multicenter score was 0.84. This was significantly better than the areas of the other four scores which ranged from 0.72 to 0.75. The cut-off levels derived from the five ROC curves achieved a sensitivity that ranged from 74% (Sassone score) to 88% (De Priest score > or = 5), and a specificity from 40% (De Priest) to 67% (multicenter); the highest positive predictive value was 41% (multicenter). With a cut-off level of 9, the accuracy of the multicenter score was significantly better than the scores of Granberg and De Priest (McNemar's test p < 0.0001). Similar results were obtained in 207 ovarian masses of < or = 5 cm in mean diameter, and when 19 borderline and 11 stage 1 cancers only were considered. For the clinical purposes of a screening test we also checked a possible cut-off level of > or = 8, which increased the sensitivity to 93% with a drop of specificity to 56%. With the use of the same criteria for the scores of the different authors, the following values were obtained for sensitivity: 96%, 81%, 93% and 90%; and for specificity: 23%, 56%, 28% and 49%. The multicenter score performed well at distinguishing malignant from benign lesions, and was better than the other four traditional scores, for both large and small masses. This was mainly due to the introduction of two criteria that allowed correction for typical dermoids and endohemorrhagic corpora lutea. A completely reliable differentiation of benign from malignant masses cannot be obtained by sonographic imaging alone.