Norbert Stachowicz

Proliferation and maturation of intratumoral blood vessels in women with malignant ovarian tumors assessed with cancer stem cells marker nestin and platelet derived growth factor PDGF-B

OBJECTIVES Platelet-derived growth factor B (PDGF-B) and nestin have been suggested to be useful in the assessment of neoangiogenesis in malignant ovarian masses. We aimed to investigate a possible association of these markers with newly formed microcapillaries and perivascular cells in ovarian tumors. MATERIAL AND METHODS Microvessel density (MVD) and pericytes were studied in 82 women with ovarian neoplasms, including 7 benign cysts, 7 borderline masses, 64 epithelial ovarian cancers and 4 other malignant ovarian tumors. Immunohistochemical staining included antibodies to CD34, PDGF-B and nestin. RESULTS Median values of CD34-positive and nestin-positive MVD were: 24,5 (range:17-32) and 21 (range: 12-31), respectively. No significant correlation between intratumoral CD-34 positive MVD and nestin-positive MVD was found. Benign and borderline lesions more frequently than malignant tumors displayed low or medium values of nestin-positive MVD (p = 0.01). Histological grading of malignant tumors was associated with nestin-positive MVD (p = 0.01). Nestin expression in tumor cells was not correlated with tumor grade or histological subtype. PDGF-B expression was found in tumor microves-sels in 72% of cases (59/82). High expression of PDGF in pericapillary cells was strongly associated with high expression of this marker in cancer cells (p = 0.007). Significant correlations between PDGF-B and nestin expression in malignant tumor microvessels were also found (p = 0.04). Nestin and PDGF-B expressions were strongly associated with high grade tumors when compared to low grade or benign masses. CONCLUSIONS We conclude that the assessment of PDGF-B and nestin-positive MVD could be used to identify only highly active, angiogenic malignant ovarian masses, where tumor vasculature is formed.

Prognostic significance of TEM7 and nestin expression in women with advanced high grade serous ovarian cancer

OBJECTIVES Tumor endothelial marker 7 (TEM7) and nestin have been proposed to be new candidates for neoangiogenesis assessment. Nestin is also cancer stem cells marker in various malignant tumors. AIMS To investigate the expression of TEM7, nestin and nestin-related microvessel density (MVD) in high-grade serous ovarian cancer samples and to study their correlation with overall survival (OS) and disease-free survival (DFS) times. MATERIAL AND METHODS Tumor samples obtained from 70 women with FIGO IIIc/IV ovarian serous cancer were studied with immunohistochemistry. RESULTS Patients median age was 54 yrs (range: 29-72 years), 86% died of the disease with median OS = 28.5 months and median DFS = 10 months (3 years DFS = 19%; 5 years. DFS = 13.8%). High nestin expression was found in 16 (23%) patients with 3 years and 5 years OS of 14% and 0%. In low-nestin expression group OS and DFS were 42% and 25%, respectively. Median nestin-MVD (16, range:12-23) was not correlated with cancer cells nestin expression and with both DFS and OS. High TEM7 expression was found in 29 women (41%) of whom 21 (72%) died of the disease. A 5-year OS in these women was 27% as compared to 8% in low TEM7 expression group, but TEM7 presence had no association with nestin, nestin-MVD and both OS and DFS. CONCLUSIONS Nestin as a marker of cancer stem cells may assist in the prediction of OS and DFS in women with high grade serous ovarian cancer. Nestin may also be considered a novel therapeutic target for antiangiogenic agents.

The use of sonographic subjective tumor assessment, IOTA logistic regression model 1, IOTA Simple Rules and GI-RADS system in the preoperative prediction of malignancy in women with adnexal masses

BACKGROUND Sonography based methods with various tumor markers are currently used to discriminate the type of adnexal masses. OBJECTIVE To compare the predictive value of selected sonography-based models along with subjective assessment in ovarian cancer prediction. MATERIAL AND METHODS We analyzed data of 271 women operated because of adnexal masses. All masses were verified by histological examination. Preoperative sonography was performed in all patients and various predictive models includ¬ing IOTA group logistic regression model LR1 (LR1), IOTA simple ultrasound-based rules by IOTA (SR), GI-RADS and risk of malignancy index (RMI3) were used. ROC curves were constructed and respective AUCs with 95% CIs were compared. RESULTS Of 271 masses 78 proved to be malignant including 6 borderline tumors. LR1 had sensitivity of 91.0%, specificity of 91.2%, AUC = 0.95 (95% CI: 0.92-0.98). Sensitivity for GI-RADS for 271 patients was 88.5% with specificity of 85% and AUC = 0.91 (95% CI: 0.88-0.95). Subjective assessment yielded sensitivity and specificity of 85.9% and 96.9%, respectively with AUC = 0.97 (95% CI: 0.94-0.99). SR were applicable in 236 masses and had sensitivity of 90.6% with specificity of 95.3% and AUC = 0.93 (95% CI 0.89-0.97). RMI3 was calculated only in 104 women who had CA125 available and had sensitivity of 55.3%, specificity of 94% and AUC = 0.85 (95% CI: 0.77-0.93). CONCLUSIONS Although subjective assessment by the ultrasound expert remains the best current method of adnexal tumors preoperative discrimination, the simplicity and high predictive value favor the IOTA SR method, and when not applicable, the IOTA LR1 or GI-RADS models to be primarily and effectively used.

OC169: Multivariate Adaptive Regression Splines (MARS) statistical modeling of clinical and sonographic data for the preoperative classification of adnexal tumors

Echogenic ovarian foci (EOF) are common ultrasound findings of unclear significance. Objectives: to follow up natural course of EOF and to determine potential for malignant transformation. Materials and Methods: Sixty five patients with EOF in one or both ovaries were followed with yearly pelvic ultrasound for 10 years. Results: EOF were bilateral in 53 patients, unilateral in 12 patients. EOF had clustered pattern in 83 ovaries and were singular in 35 ovaries. EOF were peripheral in 67 ovaries, had central location in 18 and had mixed distribution in 33 ovaries. During longitudinal follow up EOF stayed unchanged in 99 ovaries, increased in size in 12, decreased or became undetectable in 7 ovaries. Ovarian specimens were obtained in 6 patients (total 9 ovaries) who had gynecologic surgery for reasons unrelated to EOF. Epithelial inclusion cysts were detected in 5 ovaries, simple calcifications in 4 ovaries. None of the patients developed ovarian malignancy over 10-year observation period. Conclusion: EOF are benign findings and their appearance changes over time. In our series EOF did not signify ovarian pathology and required no follow-up.

OC230: Three-dimensional sonography and VEGF/VEGF receptor concentrations assessment in women with benign and malignant endometrial changes

were then calculated. All suspected recurrences underwent surgery and a definitive histological diagnosis was always obtained. Results: Recurrence of BOT was found in 6/44 women (five seropapillary and one mucinous). A unilocular solid cystic aspect was detected in every case; only one papillary projection was found in three cases and two papilla in three cases. The mean height of these projections was 6 (4–7) mm and mean volume 0.50 (0.17–1.34) mL. No blood flow was observed in the solid components and in the cystic wall. Mean papillary MG was 84.2 (68.5–96.6). Mean diameter of relapses was 15.8 (10–28) mm and mean volume 5.89 (0.84–14.5) mL. The ratio between papillary volume and cystic volume was 15.81 (4.8–27)%. Conclusions: Early ultrasound patterns of recurrent BOT seem to be a small unilocular solid cyst with well represented solid components without detectable blood flow. The knowledge of these features may avoid late diagnosis of recurrences or misdiagnosis with functional ovarian cysts in fertile women.

OC197: Prospective validation of artificial intelligence-derived prognostic models based on 2D and 3D sonography in the differentiation of ovarian tumors

I concentration. Cardiac troponin I (cTnI) is a specific marker of myocardial injury in adults and children. Perinatal asphyxia can cause cardiac dysfunction. Methods: Some 161 samples among fetuses from pathological pregnancies were collected. Twenty-two had an elevated level of cTnI (above 0.1 ng/mL). Disorders in pregnancy, date of gestation, Doppler flow velocimetry in the ductus venosus (DV) and umbilical artery (AU) and vein (DV), mode of delivery, Apgar score and respiratory status after birth were evaluated. cTnI was determined on a dimension clinical chemistry system. Results: There were 22 newborns with a raised level of TnI: seven (31.8%) with SGA, five (22.2%) with fetal cardiac problems (arrhythmia, structural and functional abnormalities), nine (40.9%) with abnormal biophysical test results (abnormal Doppler velocimetry, computerized cardiotocography, biophysical profile score) and six (27.2%) whose mothers who had disorders (diabetes mellitus, hypertension). Results are shown in the table. Median gestational age at delivery was 36.6 (range, 27–43) weeks. Seventeen (77.2%) patients had a Cesarean section. The range of TnI blood concentration was 0.11–6.66 ng/mL in this group. Five (22.7%) had umbilical pH below 7.25. Conclusions: A high level of cTnI was associated with several disorders that could have led to fetal asphyxia. More detailed fetal heart examination is necessary to prove that fetal asphyxia had an impact on heart function.

OP19.03: Three-dimensional sonography with 3D vascular and blood flow indices and microvessel density assessment in women with endometrial cancer

the bladder. One patient had benign endometrial polyp and two had endometrial thickness more than 3 mm. Conclusions: Abdel Fattah et al reported incidence of 1.07% and 0.7% for bladder tumors and bladder cancers respectively in patients referred with PMB. SIGN guidelines suggest TVUS as the first line investigation tool for majority of patients, diagnostic hysteroscopy for patients had abnormal thickness, presence of pathology or patients on tamoxifen. Datta et al reported 63% sensitivity and 99% specificity for US scan in the diagnosis of bladder cancer in patients with hematuria. We believe though rare, possibility of bladder pathology should be considered in women with PMB. Also, in cases of recurrent ‘‘PMB’’ and urinary symptoms, alternate pathology such as bladder carcinoma should be considered and TVUS is very useful in such circumstances. TVUS as a first line investigation potentially offered early detection and treatment of bladder cancer in our cohort of patients.

OC153: Multilayer perceptrons (MLP) and Bayesian neural networks (BN) in the 2D and 3D sonographic and clinical data analysis used for preoperative adnexal mass classification

Inter-observer mean difference was −0.04 mm (95% confidence interval −0.8, 0.71). The isthmal Z-scores were calculated in a two-stage process: 1. Predicted width isthmus: ln (predicted cardiac dimension) = m ln (femur length) + c; 2. Z-score: [ln (measured cardiac dimension) – ln (predicted cardiac dimension)]/root mean standard error (MSE) (where c (intercept) = −0.4988, m (multiplier) = 0.9504, root MSE = 0.16384). Conclusions: We have defined Z-scores based on femoral length for the fetal aortic isthmus measured in the three-vessel view. For cases of suspected isolated fetal coarctation, these Z-scores may be helpful in longitudinal assessment of the arch and may aid prenatal diagnosis.

OC16.05: Sonoangiography with pulsed and color Doppler blood flow measurements and microvessel density assessment in malignant ovarian tumors

The outcome measure was the histological classification of excised tissues as malignant or benign. Over 50 end-point variables were prospectively defined and recorded for analysis. By utilizing a multicenter approach any model developed is likely to be more generally applicable outside the context of the study population. Several new mathematical models were developed and tested. The results were also compared with results obtained with older models and with subjective assessment of experienced clinicians. This presentation will extensively cover the benefits and limitations of mathematical models.

OC236: Predicting adnexal malignancy: application of multivariate logistic regression analysis to transvaginal three-dimensional sonography with 3D blood flow and vascularity assessment

would have been detected. An alternative cut-off value of 35 U/ml would have resulted in a detection rate of 33%. Conclusions: Transvaginal ultrasonography can effectively detect intra-ovarian cancer and tumours of borderline malignancy in women with a family history of the disease. The level of serum CA125 can be used to select women for ultrasonography, but the detection rate for early cancers would be reduced.