Role of CA125/CEA ratio and ultrasound parameters in identifying metastases to the ovaries in patients with multilocular and multilocular-solid ovarian masses.

OBJECTIVES: To investigate ultrasound features and the best cut-off value of the cancer antigen 125/carcinoembryonic antigen (CA125/CEA) ratio to discriminate ovarian metastases from benign and primary malignant ovarian neoplasms in two selected groups of morphological ovarian masses, namely multilocular masses with five or more locules and multilocular-solid masses. METHODS: Patients with multilocular (five or more locules) or multilocular-solid ovarian masses, operated on within 3 months of ultrasound examination, and with tumor markers (CEA and CA125) available at diagnosis, were identified retrospectively from three ultrasound centers. The masses were described using the International Ovarian Tumor Analysis (IOTA) terminology. Ultrasound and clinical characteristics were compared between those with an ovarian neoplasm (including benign and primary malignant neoplasms) and those with an ovarian metastasis. Receiver-operating characteristics curve (ROC) analysis was used to evaluate the ability of CA125, CEA and CA125/CEA to differentiate between ovarian neoplasms and ovarian metastases, and their predictive performance was assessed. RESULTS: In total, 350 (88.4%) patients with an ovarian neoplasm (including 99 benign, 43 borderline and 197 primary epithelial ovarian carcinomas, seven malignant rare tumors and four other types of invasive ovarian tumor) and 46 (11.6%) patients with an ovarian metastasis were analyzed. On ultrasound examination, ovarian neoplasms were smaller than ovarian metastases (median largest diameter, 97 (range, 20-387) mm vs 146 (range, 43-259) mm, respectively; P < 0.0001) and presented with a lower number of cysts with > 10 locules (18.9% vs 54.3%; P < 0.0001). ROC curve analysis showed that the best cut-off value of CEA for distinguishing between ovarian neoplasms and ovarian metastases was 2.33 ng/mL. The predictive performance of this CEA cut-off value was: area under the curve (AUC), 0.791 (95% CI, 0.711-0.870); accuracy, 73.7%; sensitivity, 73.1%; specificity, 78.3%; positive predictive value (PPV), 96.2%; and negative predictive value (NPV), 27.7%. The best cut-off value of CA125/CEA for distinguishing between ovarian neoplasms and ovarian metastases was 11.92. The predictive performance of this CA125/CEA cut-off value was: AUC, 0.758 (95% CI, 0.683-0.833); accuracy, 79.8%; sensitivity, 82.3%; specificity, 60.9%; PPV, 94.1%; and NPV, 31.1%. CONCLUSIONS: CA125/CEA ratio and CEA alone did not show any significant difference in their ability to distinguish between ovarian neoplasms (including benign and malignant) and ovarian metastases in masses with multilocular and those with multilocular-solid morphology. Therefore, in this morphological subgroup of ovarian masses, CEA alone is sufficient to differentiate between ovarian neoplasms and ovarian metastases. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

International Endometrial Tumor Analysis (IETA) terminology in women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm: agreement and reliability study.

OBJECTIVE: To estimate intra- and interrater agreement and reliability with regard to describing ultrasound images of the endometrium using the International Endometrial Tumor Analysis (IETA) terminology. METHODS: Four expert and four non-expert raters assessed videoclips of transvaginal ultrasound examinations of the endometrium obtained from 99 women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm but without fluid in the uterine cavity. The following features were rated: endometrial echogenicity, endometrial midline, bright edge, endometrial-myometrial junction, color score, vascular pattern, irregularly branching vessels and color splashes. The color content of the endometrial scan was estimated using a visual analog scale graded from 0 to 100. To estimate intrarater agreement and reliability, the same videoclips were assessed twice with a minimum of 2 months' interval. The raters were blinded to their own results and to those of the other raters. RESULTS: Interrater differences in the described prevalence of most IETA variables were substantial, and some variable categories were observed rarely. Specific agreement was poor for variables with many categories. For binary variables, specific agreement was better for absence than for presence of a category. For variables with more than two outcome categories, specific agreement for expert and non-expert raters was best for not-defined endometrial midline (93% and 96%), regular endometrial-myometrial junction (72% and 70%) and three-layer endometrial pattern (67% and 56%). The grayscale ultrasound variable with the best reliability was uniform vs non-uniform echogenicity (multirater kappa (κ), 0.55 for expert and 0.52 for non-expert raters), and the variables with the lowest reliability were appearance of the endometrial-myometrial junction (κ, 0.25 and 0.16) and the nine-category endometrial echogenicity variable (κ, 0.29 and 0.28). The most reliable color Doppler variable was color score (mean weighted κ, 0.77 and 0.69). Intra- and interrater agreement and reliability were similar for experts and non-experts. CONCLUSIONS: Inter- and intrarater agreement and reliability when using IETA terminology were limited. This may have implications when assessing the association between a particular ultrasound feature and a specific histological diagnosis, because lack of reproducibility reduces the reliability of the association between a feature and the outcome. Future studies should investigate whether using fewer categories of variable or offering practical training could improve agreement and reliability. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

PRospective Imaging of CErvical cancer and neoadjuvant treatment (PRICE) study: role of ultrasound to assess residual tumor in locally advanced cervical cancer patients undergoing chemoradiation and radical surgery.

OBJECTIVE: To determine the diagnostic performance of two-dimensional (2D) ultrasound parameters, three-dimensional (3D) power Doppler and contrast-enhanced indices in detecting residual disease in locally advanced cervical cancer patients triaged to neoadjuvant treatment followed by radical surgery. METHODS: Between October 2010 and June 2014, we screened 108 women with histologically documented locally advanced cervical cancer Stage IB2-IVA, of whom 88 were included in the final analysis. 2D ultrasound parameters, 3D power Doppler and contrast-ultrasound parameters were assessed 5 weeks after the end of neoadjuvant chemoradiation therapy. The pathological response was defined as complete (absence of any residual tumor after treatment) or partial (including microscopic and/or macroscopic residual tumor at pathology examination). The two response groups were compared and receiver-operating characteristics (ROC) curves generated to determine the best cut-off value of sonographic tumor diameter to predict residual disease. Histology was considered as reference. RESULTS: Complete pathological response to chemoradiation was observed in 40 (45.5%) patients and partial response in 48 (54.5%). The presence of residual disease, as confirmed at pathology examination, was detected by 2D grayscale ultrasound with a sensitivity of 64.6% and specificity of 65%. Color Doppler examination in the cases with lesions visualized on grayscale imaging detected the presence of residual disease, confirmed at pathology, with a sensitivity of 87.1% and specificity of 21.4%. The best area under the ROC curve (0.817) was for the detection of pathological residual disease of at least 6 mm in diameter, using a cut-off value of 12 mm for the largest tumor diameter assessed using 2D grayscale ultrasound (sensitivity, 95%; specificity, 70.6%). Neither 3D vascular indices nor contrast-ultrasound parameters obtained for lesions suspected at ultrasound following chemoradiation differed significantly between patients with histological complete and those with partial response. CONCLUSIONS: Our results show that grayscale and color Doppler ultrasound have a low level of diagnostic performance in detecting residual disease after neoadjuvant chemoradiation in patients with locally advanced cervical cancer. The best performance was achieved in detection of macroscopic (≥ 6 mm) residual disease. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Clinical and ultrasound characteristics of surgically removed adnexal lesions with largest diameter ≤ 2.5 cm: a pictorial essay.

OBJECTIVES: To describe the ultrasound characteristics, indications for surgery and histological diagnoses of surgically removed adnexal masses with a largest diameter of ≤ 2.5 cm (very small tumors), to estimate the sensitivity and specificity of diagnosis of malignancy by subjective assessment of ultrasound images of very small tumors and to present a collection of ultrasound images of surgically removed very small tumors, with emphasis on those causing diagnostic difficulty. METHODS: Information on surgically removed adnexal tumors with a largest diameter of ≤ 2.5 cm was retrieved from the ultrasound databases of seven participating centers. The ultrasound images were described using the International Ovarian Tumor Analysis terminology. The original diagnosis, based on subjective assessment of the ultrasound images by the ultrasound examiner, was used to calculate the sensitivity and specificity of diagnosis of malignancy. RESULTS: Of the 129 identified adnexal masses with largest diameter ≤ 2.5 cm, 104 (81%) were benign, 15 (12%) borderline malignant and 10 (8%) invasive tumors. The main indication for performing surgery was suspicion of malignancy in 22% (23/104) of the benign tumors and in all 25 malignant tumors. None of the malignant tumors was a unilocular cyst (vs 50% of the benign tumors), all malignancies contained solid components (vs 43% of the benign tumors), 80% of the borderline tumors had papillary projections (vs 21% of the benign tumors and 20% of the invasive malignancies) and all invasive tumors and 80% of the borderline tumors were vascularized on color/power Doppler examination (vs 44% of the benign tumors). The ovarian crescent sign was present in 85% of the benign tumors, 80% of the borderline tumors and 50% of the invasive malignancies. The sensitivity of diagnosis of malignancy by subjective assessment of ultrasound images was 100% (25/25) and the specificity was 86% (89/104). Excluding unilocular cysts, the specificity was 71% (37/52). Analysis of images illustrated the difficulty in distinguishing benign from borderline very small cysts with papillations and benign from malignant very small well vascularized (color score 3 or 4) solid adnexal tumors. CONCLUSIONS: Very small malignant tumors manifest generally accepted ultrasound signs of malignancy. Small unilocular cysts are usually benign, while small non-unilocular masses, particularly ones with solid components, incur a risk of malignancy and pose a clinical dilemma. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Preoperative prediction of lymph node metastasis and deep stromal invasion in women with invasive cervical cancer: prospective multicenter study using 2D and 3D ultrasound.

OBJECTIVES: To determine how various objective two-dimensional (2D) and three-dimensional (3D) ultrasound parameters allow prediction of deep stromal tumor invasion and lymph node involvement, in comparison to subjective ultrasound assessment, in women scheduled for surgery for cervical cancer. METHODS: This was a prospective multicenter trial including 104 women with cervical cancer at FIGO Stages IA2-IIB, verified histologically. Patients scheduled for surgery underwent a preoperative ultrasound examination. The value of various 2D (size, color score) and 3D (volume, vascular indices) ultrasound parameters was compared to that of subjective assessment in the prediction of deep stromal tumor invasion and lymph node involvement. Histology obtained from radical hysterectomy or trachelectomy and pelvic lymphadenectomy was considered as the gold standard for assessment. RESULTS: All women underwent pelvic lymphadenectomy, with 99 (95%) undergoing subsequent radical surgery; five underwent only pelvic lymphadenectomy because of the presence of a positive sentinel lymph node. Women with deep stromal invasion or lymph node involvement had significantly larger tumors (diameter and volume) but there was no correlation with vascular indices measured on 3D ultrasound. Subjective evaluation was superior (AUC, 0.93; sensitivity, 90.5%; specificity, 97.2%) in the prediction of deep stromal invasion when compared to any objective measurement technique, with maximal tumor diameter at 20.5-mm cut-off (AUC, 0.83; sensitivity, 90.5%; specificity, 61.1%) and 3D tumor volume at 9.1-mm(3) cut-off (AUC, 0.85; sensitivity, 79.4%; specificity, 83.3%) providing the best performance among the objective parameters. Both subjective assessment and objective measurements were poorly predictive of lymph node involvement. CONCLUSIONS: In women with cervical cancer, subjective ultrasound evaluation allowed better prediction of deep stromal invasion than did objective measurements; however, neither subjective evaluation nor objective parameters were adequate to predict lymph node involvement. 3D vascular indices were ineffective in the prediction of advanced stages of the disease.

Agreement of two-dimensional and three-dimensional transvaginal ultrasound with magnetic resonance imaging in assessment of parametrial infiltration in cervical cancer.

OBJECTIVES: To compare two-dimensional (2D) and three-dimensional (3D) transvaginal ultrasound with magnetic resonance imaging (MRI) as the gold standard in assessment of parametrial infiltration of cervical cancer and to determine if all parts of the cervix are equally assessable with ultrasound. METHODS: Patients with macroscopically evident and histologically confirmed cervical cancer were staged using International Federation of Gynecology and Obstetrics (FIGO) criteria and underwent MRI and 2D and 3D ultrasound examination before treatment. When assessing parametrial infiltration with 3D ultrasound and MRI, the cervix was (virtually) divided into three cylinders (cranial, middle and caudal) of equal size and each cylinder was then divided into six sectors in a clockwise manner following a consensus between radiologists and ultrasound examiners. The presence and the extent of parametrial invasion were recorded for each sector. Results of 2D ultrasound, 3D ultrasound and MRI were compared and reported in terms of percentage agreement and kappa value. RESULTS: A total of 29 consecutive patients were included in the study. The percentage agreement between 2D ultrasound and MRI in assessing parametrial infiltration (yes or no) was 76% (kappa, 0.459) and that between 3D ultrasound and MRI was 79% (kappa, 0.508). The results of 2D ultrasound showed the following agreement with those of MRI: 90% for the ventral parametrium (kappa, 0.720), 72% for the right lateral parametrium (kappa, 0.494), 69% for the left lateral parametrium (kappa, 0.412) and 58.5% for the dorsal parametrium (kappa, 0.017). The results of 3D ultrasound showed the following agreement with those of MRI: 62.5% for the ventral parametrium (kappa, 0.176), 81% for the right lateral parametrium (kappa, 0.595), 70% for the left lateral parametrium (kappa, 0.326) and 52% for the dorsal parametrium (kappa, 0.132). The best agreement between 3D ultrasound and MRI was for the middle cervical cylinder (76%; kappa, 0.438) and the poorest agreement was for the caudal cylinder (42%; kappa, 0.125). CONCLUSION: The results of 2D and 3D ultrasound showed similar moderate agreement with MRI; 2D and 3D ultrasound examinations are less costly and more readily available than MRI and should be considered in the preoperative work-up for cervical cancer.

Intra- and interobserver agreement with regard to describing adnexal masses using International Ovarian Tumor Analysis terminology: reproducibility study involving seven observers.

OBJECTIVES: To estimate intraobserver repeatability and interobserver agreement in assessing the presence of papillary projections in adnexal masses and in classifying adnexal masses using the International Ovarian Tumor Analysis terminology for ultrasound examiners with different levels of experience. We also aimed to identify ultrasound findings that cause confusion and might be interpreted differently by different observers, and to determine if repeatability and agreement change after consensus has been reached on how to interpret 'problematic' ultrasound images. METHODS: Digital clips (two to eight clips per adnexal mass) with gray-scale and color/power Doppler information of 83 adnexal masses in 80 patients were evaluated independently four times, twice before and twice after a consensus meeting, by four experienced and three less experienced ultrasound observers. The variables analyzed were tumor type (unilocular, unilocular solid, multilocular, multilocular solid, solid) and presence of papillary projections. Intraobserver repeatability was evaluated for each observer (percentage agreement, Cohen's kappa). Interobserver agreement was estimated for all seven observers (percentage agreement, Fleiss kappa, Cohen's kappa). RESULTS: There was uncertainty about how to define a solid component and a papillary projection, but consensus was reached at the consensus meeting. Interobserver agreement for tumor type was good both before and after the consensus meeting, with no clear improvement after the meeting, mean percentage agreement being 76.0% (Fleiss kappa, 0.695) before the meeting and 75.4% (Fleiss kappa, 0.682) after the meeting. Interobserver agreement with regard to papillary projections was moderate both before and after the consensus meeting, with no clear improvement after the meeting, mean percentage agreement being 86.6% (Fleiss kappa, 0.536) before the meeting and 82.7% (Fleiss kappa, 0.487) after it. There was substantial variability in pairwise agreement for papillary projections (Cohen's kappa, 0.148-0.787). Intraobserver repeatability with regard to tumor type was very good and similar before and after the consensus meeting (agreement 87-95%, kappa, 0.83-0.94). With regard to papillary projections intraobserver repeatability was good or very good both before and after the consensus meeting (agreement 88-100%, kappa, 0.64-1.0). CONCLUSIONS: Despite uncertainty about how to define solid components, interobserver agreement was good for tumor type. The interobserver agreement for papillary projection was moderate but very variable between observer pairs. The term 'papillary projection' might need a more precise definition. The consensus meeting did not change inter- or intraobserver agreement.

Intra- and interobserver reproducibility of assessment of Doppler ultrasound findings in adnexal masses.

OBJECTIVES: To estimate intra- and interobserver reproducibility and reliability of assessment of the color content in adnexal masses at color/power Doppler ultrasound examination for observers with different levels of experience, and to determine if they change after a consensus meeting. METHODS: Digital clips with color/power Doppler information on 103 adnexal masses were evaluated independently four times, twice before and twice after a consensus meeting, by four experienced and three less experienced ultrasound examiners. The color content of the adnexal mass was estimated using the International Ovarian Tumor Analysis color score and a 100-mm visual analog scale (VAS score). Intraobserver repeatability was estimated for each observer. Interobserver agreement was estimated for the four most experienced observers (six pairs), for the three less experienced observers (three pairs), and for four other pairs of observers, each pair consisting of one of the experienced and one of the less-experienced observers. RESULTS: Intra- and interobserver agreement for the color score was moderate to very good, percentage agreement ranging from 48 to 82.5% (kappa, 0.52-0.82) before and from 59 to 90% (kappa, 0.60-0.88) after the consensus meeting. For seven of 13 pairs of observers, interobserver agreement improved after the consensus meeting. Intraobserver intraclass correlation coefficient (ICC) values for the VAS score ranged from 0.80 to 0.92 before and from 0.75 to 0.94 after the consensus meeting, but limits of agreement were wide (± 20-35 mm). For six of the seven observers the ICC values were higher after the consensus meeting than before. Interobserver ICC values for the VAS score ranged from 0.77 to 0.88 before and from 0.77 to 0.91 after the consensus meeting, but limits of agreement were wide (± 30-40 mm). For 10 of 13 pairs of observers the ICC values improved after the consensus meeting. CONCLUSIONS: Intra- and interobserver agreement for the color score was good, especially after the consensus meeting, but there is room for improvement. VAS score results varied substantially within and between observers both before and after the consensus meeting. General consensus needs to be reached about how to interpret color/power Doppler ultrasound findings in adnexal masses.

Phase II study of NGR-hTNF in combination with doxorubicin in relapsed ovarian cancer patients.

BACKGROUND: The NGR-hTNF (asparagine-glycine-arginine-human tumour necrosis factor) is able to promote antitumour immune responses and to improve the intratumoural doxorubicin uptake by selectively damaging tumour blood vessels. METHODS: Patients progressing after ≥ 1 platinum/taxane-based regimen received NGR-hTNF 0.8 µg m(-2) and doxorubicin 60 mg m(-2) every 3 weeks. Primary endpoint was a Response Evaluation Criteria in Solid Tumors-defined response rate with a target of more than 6 out of 37 responding patients. RESULTS: A total of 37 patients with platinum-free interval lower than 6 months (PFI<6; n=25), or between 6 and 12 months (PFI=6-12; n=12) were enrolled. Median baseline peripheral blood lymphocyte count (PBLC) was 1.6 per ml (interquartile range, 1.2-2.1). In all, 18 patients (49%) received more than 6 cycles. Febrile neutropaenia was registered in one patient (3%). Among 35 assessable patients, 8 (23%; 95% CI 12-39%) had partial response (2 with PFI<6; 6 with PFI=6-12) and 15 (43%) had stable disease (10 with PFI<6; 5 with PFI=6-12). Median progression-free survival (PFS) was 5.0 months for all patients, 3.8 months for patients with PFI<6, and 7.8 months for patients with PFI=6-12. Median overall survival (OS) was 17.0 months. Patients with baseline PBLC higher than the first quartile had improved PFS (P=0.01) and OS (P=0.001). CONCLUSION: Tolerability and activity of this combination warrant further randomised testing in patients with PFI<6. The role of PBLC as a blood-based biomarker deserves further investigation.

The sonographic prediction of invasive carcinoma in unilocular-solid ovarian cysts in premenopausal patients: a pilot study.

BACKGROUND: Unilocular-solid ovarian cysts are a rare but challenging pathology in young women, with a desire to spare their fertility. In these cases, the risks of borderline and invasive disease are around 10 and 20%, respectively. No ultrasound rule has yet demonstrated the ability to discriminate with high accuracy, a borderline tumor from a benign tumor or 'invasive tumor'. The aim of this study was to assess the predictive performance of different ultrasound parameters in differentiating benign and borderline tumors versus invasive malignant tumors in premenopausal patients with unilocular-solid ovarian masses. METHODS: Women aged ≤ 50 years with unilocular-solid adnexal masses with a maximum diameter ≤ 10 cm, undergoing surgery in our department within 3 months from ultrasound examination, were included in this retrospective study. A standardized ultrasound examination technique and predefined definitions of ultrasound characteristics were used. The results of ultrasound examination using gray scale and color Doppler were compared with the histological examination of the respective surgical specimens. RESULTS: The study included 51 patients. On histological examination, 36 (70%) lesions were classified as benign, 10 (20%) as borderline ovarian tumors and 5 (10%) as invasively malignant tumors. In receiver-operating characteristic curve analysis, the best cut-off for the largest solid component with regard to discriminating non-invasive (benign or borderline) from invasive tumors was 14 mm. A largest solid component >14 mm, the presence of papillation blood flow and the combination of the two parameters provided a sensitivity of 100% and a specificity of 63, 63 and 80%, respectively. CONCLUSIONS: Transvaginal ultrasound examination seems to be able to discriminate between invasive and non-invasive tumors in the premenopausal patients with unilocular-solid adnexal masses. Because of the retrospective nature of the study, further prospective clinical trials are needed to confirm the accuracy of the selected sonographic parameters in discriminating the invasive and non-invasive adnexal tumors.

Ultrasound evaluation of intra-abdominal sites of disease to predict likelihood of suboptimal cytoreduction in advanced ovarian cancer: a prospective study.

OBJECTIVES: To analyze in advanced ovarian cancer patients the ability of ultrasound to evaluate the extent of intra-abdominal disease and to predict the likelihood of suboptimal cytoreduction. METHODS: Into this prospective study, 147 patients with advanced ovarian cancer were enrolled consecutively between January 2005 and October 2008. All patients underwent standard laparotomy and maximal surgical effort was attempted. To create a new scoring system to predict suboptimal cytoreduction we considered the following sonographic parameters: peritoneal carcinomatosis, bowel mesentery involvement, omental involvement, massive pelvic involvement, ascites and liver and/or spleen metastases. Those parameters achieving a negative predictive value ≥ 50% and a positive predictive value ≥ 50% in predicting suboptimal cytoreduction were included in the ultrasound scoring system, which was then calculated for each patient. RESULTS: Ultrasound allowed a virtually conclusive diagnosis of massive pelvic involvement (sensitivity, 94%; specificity, 97%), parenchymal liver metastases of any size (sensitivity, 93%; specificity, 98%) and ascites (sensitivity, 98%; specificity, 97%) and a very reliable diagnosis of peritoneal carcinomatosis (sensitivity, 91%; specificity, 88%) and omental involvement (sensitivity, 94%; specificity, 90%), whereas it was not very good at excluding parenchymal spleen metastases or splenic hilum involvement (sensitivity, 75%; specificity, 98%) and bowel mesentery involvement (sensitivity, 67%; specificity, 88%). Ultrasound-assessed peritoneal carcinomatosis, bowel mesentery involvement, omental involvement, massive pelvic involvement and ascites were included in our ultrasound score (which had a range of 0-6 points). With a cut-off value of > 5, the sensitivity and specificity of the ultrasound score with regard to prediction of suboptimal cytoreduction were 31% (20/64) and 92% (46/50), respectively. CONCLUSIONS: Ultrasound examination is able to assess intra-abdominal disease in advanced ovarian cancer patients, with satisfactory concordance with laparotomic findings. Our ultrasound score can predict suboptimal cytoreduction and might be clinically useful.

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.

Early-stage cervical cancer: agreement between ultrasound and histopathological findings with regard to tumor size and extent of local disease.

OBJECTIVES: To determine the agreement between ultrasound and histological examination of the cervix in patients with early stage cervical cancer with regard to tumor size and local extent of the disease. METHODS: Eighteen patients with histologically proven cervical cancer Stage IB1-IIA according to traditional clinical staging (FIGO 1988) who were scheduled for radical surgery underwent a standardized transvaginal ultrasound examination. The maximum tumor length, anteroposterior tumor diameter, tumor width, tumor area, depth of cervical stroma invasion, and the minimal thickness of tumor-free cervical stroma on sagittal and transverse planes through the cervix were measured, and the local extent of the disease within the parametria and vagina were evaluated. The surgical specimens were examined using a specifically devised method of histopathological examination. The results of the ultrasound and histopathological examinations were compared. RESULTS: Limits of agreement were wide and the intraclass correlation coefficient (ICC) was low (0.51-0.58) for three of the four measurements taken to represent the minimal depth of tumor-free cervical stroma, i.e. the results of the measurements taken posteriorly and laterally. However, the limits of agreement were narrower and the ICC values were higher (0.74-0.92) for the depth of cervical stroma invasion and for the tumor size measurements. Histological examination revealed parametrial cancer infiltration in four patients, which was detected during ultrasound examination, with no false-positive results. CONCLUSIONS: Transvaginal sonography is acceptably accurate for evaluation of tumor size and depth of cervical stroma invasion in clinical practice.

Ovarian cancer arising in endometrioid cysts: ultrasound findings.

OBJECTIVES: To describe sonographic characteristics of malignant transformation in endometrioid cysts. METHODS: Women with a histological diagnosis of ovarian endometrioid cysts, borderline tumors arising in endometrioid cysts and carcinoma arising in endometrioid cysts, preoperatively examined sonographically, were included in this retrospective study. Gray-scale and Doppler ultrasound characteristics of the endometrioid cysts were compared with those of the borderline tumors and primary cancers arising in endometrioid cysts. The performance of an experienced examiner in classifying the masses was also assessed. RESULTS: Of 324 cases collected for the study, 309 (95.3%) lesions were classified as endometrioid cysts, four (1.2%) as borderline tumors arising in endometrioid cysts and 11 (3.4%) as carcinoma arising in endometrioid cysts. Women with malignant findings (borderline ovarian tumors and cancers) were older (median age 52 (range, 28-79) years) than those with benign endometrioid cysts (median age 34 (range, 18-76) years) (P<0.0001), and the prevalence of postmenopausal status was significantly higher in malignant cases. All (15/15) malignant tumors vs. 16% (50/309) of benign tumors were characterized by the presence of solid tissue (P<0.0001). The prevalence of solid tissue with positive Doppler signals was higher in malignant tumors (100%) than in benign cysts (7.8%) (P<0.0001). Papillary projections were a more frequent sonographic feature among malignant lesions (86.7%) than among benign endometrioid cysts (11.3%) (P<0.0001); power Doppler signals were detected within the projections in 92.3% and 37.1% of malignant and benign lesions, respectively. The examiner correctly diagnosed 94.8% (293/309) of benign lesions as benign and 93.3% (14/15) of malignant lesions as malignant. The risk estimation of the examiner was 'uncertain' in three (20%) and 'probably/certainly malignant' in 12 (80%) of 15 malignant cases. CONCLUSION: Borderline tumors and carcinomas arising in endometrioid cysts show a vascularized solid component at ultrasound examination.

Sonographic characteristics of squamous cell cancer and adenocarcinoma of the uterine cervix.

OBJECTIVE: The objective of this study was to describe the sonographic characteristics of squamous cell cancer (SCC) and adenocarcinoma (AC) of the cervix using transvaginal ultrasound. METHODS: Women with early stage cervical cancer undergoing transvaginal ultrasound examination before surgery were prospectively included. The sonographic characteristics were assessed with regard to tumor morphology, vascularization, size, extension and location. Histological assessment of tumor subtype, size, growth pattern, extension and location was performed. Both sonographic and histological assessments were carried out according to a standardized protocol. RESULTS: Fifty-five women were recruited. Ten were excluded because no tumor was seen on ultrasound examination and five were excluded because radical surgery was aborted as a result of positive lymph nodes, detected using the sentinel node technique. Among the remaining 40 women, 20 had AC and 20 had SCC. At pathological examination, 34 women had tumors confined to the cervix, three had parametrial invasion and three had vaginal invasion. Hypoechogenicity was associated with SCC in 73% (11/15) of the women, while isoechogenicity indicated AC in 68% (13/19) of the women (P = 0.03). Mixed echogenicity (n = 4) showed a non-significant association with larger tumor volume (P = 0.23). Hyperechogenicity was found in two women, both of whom had the less malignant villoglandular AC. Color Doppler signals were found in all cases of AC and in 90% (18/20) of cases of SCC, compared with most normal cervical tissue in which virtually no detectable vascularization was found. CONCLUSION: We found that the sonographic appearance of SCC and AC differs. This knowledge should be useful in the clinical evaluation of cervical tumors.

Sonographic features of primary ovarian fibrosarcoma: a report of two cases.

Two cases of primary cellular fibroblastic tumor of the ovary are described, which presented a challenging clinical and histopathological differential diagnosis of primary ovarian fibrosarcoma and mitotically active cellular fibroma. On sonographic evaluation they both appeared as solid lesions with irregular margins, and on histological analysis both showed a count of 5-7 mitotic figures per 10 high-power fields. Histopathological examination of the first case was characterized by the presence of hemorrhage, necrosis and severe nuclear atypia, with a metastatic peritoneal lesion, and the eventual diagnosis was primary ovarian fibrosarcoma. The second case, however, was diagnosed as a 'mitotically active cellular fibroma' owing to the lack of substantial severe cellular atypia, hemorrhage or necrosis. We speculate that ovarian fibrosarcoma at the preoperative examination might be considered in the differential diagnosis whenever a unilateral, heterogeneous, largely round solid ovarian lesion is detected.

Transvaginal ultrasonography and magnetic resonance imaging for assessment of presence, size and extent of invasive cervical cancer.

OBJECTIVES: To prospectively assess the diagnostic performance of transvaginal ultrasound and magnetic resonance imaging (MRI), using histology as the gold standard, with regard to the presence, size, and extent of invasive cervical cancers and the detection of metastatic lymph nodes. METHODS: This was a prospective study designed to examine patients with invasive cervical cancer by means of ultrasonography and MRI within 1 week before surgery. We included patients with early cervical cancer planned for primary surgery and patients with locally advanced cervical cancer planned for surgery after neoadjuvant treatment. RESULTS: An invasive cervical cancer tumor was confirmed in the 33 patients triaged for primary surgery. A residual tumor mass was documented in 27 out of 35 patients (77%) who underwent surgery after neoadjuvant treatment, with no residual tumor in eight (23%) cases. Transvaginal ultrasound and MRI examinations showed the presence of the tumor mass in 56/60 (93%) and in 53/60 (88%) cases, respectively. Ultrasound and MRI detected the depth of stromal invasion to be greater than two-thirds with a sensitivity of 100% (16/16) and 94% (15/16) (P = 1) and a false-positive rate of 25% (13/52) and 15% (8/52) (P = 0.58), respectively. Both ultrasound and MRI provided low sensitivities (3/5, 60% and 2/5, 40% respectively, P = 1) and the same false-positive rate (7/63, 11%) for the presence of parametrial infiltration. One of the 11 patients with metastatic lymph nodes was detected at ultrasound examination (sensitivity 9%) with no false-positive cases, while MRI correctly identified three positive cases (sensitivity 27%, 3/11) with two false-positive cases (false positive rate 4%, 2/55). CONCLUSIONS: Ultrasound and MRI had similar sensitivity and specificity with regard to the parameters investigated. Ultrasound has the advantages over MRI of low cost, widespread availability and of being a relatively quick procedure. Ultrasound should be considered as a suitable diagnostic method in the preoperative work-up of cervical cancer.