Prospective external validation of IOTA three-step strategy for characterizing and classifying adnexal masses and retrospective assessment of alternative two-step strategy using simple-rules risk.

OBJECTIVES: To perform an external validation of the diagnostic performance of the three-step strategy proposed by the International Ovarian Tumor Analysis (IOTA) group for classifying adnexal masses as benign or malignant, when ultrasound is performed by non-expert sonographers in the first two steps. The second objective was to assess the diagnostic performance of an alternative strategy using simple-rules risk (SRR), instead of simple rules (SR), in the second step. METHODS: This was a prospective observational study conducted at two university hospitals, from September 2015 to August 2017, of consecutive patients diagnosed with an adnexal mass. All women were evaluated by ultrasound using the IOTA three-step strategy. Non-expert sonographers performed the first step (use of simple descriptors to classify the masses) and the second step (use of SR if the mass could not be classified in the first step); masses that could not be classified in the first two steps were categorized by an expert sonographer based on their subjective assessment (third step). The reference standard was histological diagnosis in patients who underwent surgery or at least 12 months of follow-up in cases managed expectantly. The sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratios and overall accuracy of the IOTA three-step strategy were estimated. Furthermore, we evaluated retrospectively an alternative two-step strategy using SRR in the second step to categorize the masses not classifiable with simple descriptors, classifying the lesions as being of low, intermediate or high risk for malignancy. The diagnostic performance of this strategy was estimated by calculating its sensitivity and specificity, assuming surgical intervention for intermediate- or high-risk lesions. RESULTS: The study included 283 patients (median age, 48 (range, 18-90) years), of whom 165 (58.3%) were premenopausal and 118 (41.7%) postmenopausal. Two hundred and sixteen (76.3%) women underwent surgery (154 benign and 62 malignant masses) and 67 (23.7%) were managed expectantly with serial ultrasound follow-up for at least 12 months. All expectantly managed masses were considered benign because no sonographic changes suggestive of malignancy were observed during follow-up. Simple descriptors could be applied in 126 (44.5%) masses. Of the remaining 157 lesions, 112 (39.6%) could be characterized using SR. Therefore, 238 (84.1%) masses could be classified by non-expert sonographers in the first two steps. Of the remaining 45 (15.9%) masses, all could be classified by an expert sonographer. Overall sensitivity, specificity, LR+ and LR- of the IOTA three-step strategy were 95.2%, 97.7%, 42.1 and 0.05, respectively. The diagnostic accuracy was 97.2%. Following the two-step strategy using SRR in the second step, of the 157 lesions not classified with simple descriptors, 42, 38 and 77 presented low, intermediate or high risk for malignancy, respectively. Based on this method, 210 women would have undergone surgical treatment. The sensitivity and specificity of this two-step strategy were 98.4% and 63.8%, respectively. CONCLUSIONS: The IOTA three-step strategy shows high accuracy for discriminating between benign and malignant adnexal lesions when used by non-expert sonographers. An alternative strategy using the SRR calculator in the second step might improve on this diagnostic performance by decreasing the number of surgical interventions and increasing sensitivity. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Clinical and ultrasound features of benign, borderline, and malignant invasive mucinous ovarian tumors.

OBJECTIVE: To compare clinical and sonographic features of benign, borderline, and malignant invasive mucinous ovarian tumors (MOTs). MATERIALS AND METHODS: Retrospective observational multicenter study comprising 365 women (mean age: 46.1 years) with a histologically confirmed benign, borderline or malignant invasive MOT. Clinical data (patient's age, patient's complaints), tumor markers (CA-125 and CA-1 9.9), and sonographic data (tumor size, bilaterality, morphology -unilocular, multilocular, unilocular-solid, multilocular-solid and solid-, and IOTA color score) were reviewed and compared among these three groups. Women with ultrasound evidence on intra-abdominal disease spread were excluded. RESULTS: Three hundred seventy-eight MOTs (14 women had bilateral lesions) were analyzed. Histologically, 287 tumors were benign, 51 were borderline, and 40 were malignant. No difference in patient's mean age was observed. Women with borderline or invasive tumors were less frequently asymptomatic. Tumors were larger in case of invasive lesions. Borderline and invasive tumors showed solid components and exhibited IOTA color score 3 or 4, more frequently than benign lesions (p < 0.001). However, the authors discovered that 16 out of 51 (31.4%) of borderline tumors and six out of 40 (15.0%) of invasive cancers had no solid components and a color score 1 or 2, and were considered as a benign lesion by the sonolo- gist. On the other hand, 96 out of 287 (33.4%) benign mucinous cystadenoma exhibited solid components and/or a color score of 3 or 4. CONCLUSIONS: In spite of statistical differences, the authors observed significant overlapping in ultrasound features among benign, borderline, and invasive ovarian mucinous tumors that renders a difficult accurate preoperative discrimination among these lesions.

External validation of IOTA simple descriptors and simple rules for classifying adnexal masses.

OBJECTIVE: To assess the diagnostic performance of a three-step strategy proposed by the International Ovarian Tumor Analysis (IOTA) Group for discriminating between benign and malignant adnexal masses. METHODS: This was a prospective observational study, performed at two tertiary-care university hospitals, of women diagnosed with an adnexal mass on transvaginal or transabdominal ultrasound between December 2012 and December 2014. Women were scheduled for an ultrasound evaluation, which was initially performed by non-expert examiners. The examiner had to classify the mass using 'simple descriptors' (first step) and, if not possible, using 'simple rules' (second step). For inconclusive masses, an expert examiner classified the mass according to their subjective impression (third step). Masses were managed expectantly, with serial follow-up examinations, or surgically, according to ultrasound findings and clinical symptoms. Histology was used as the reference standard. Masses that were managed expectantly with at least 1 year of follow-up were considered as benign for analytical purposes. Women with less than 1 year of follow-up were not included in the study. RESULTS: Six hundred and sixty-six women were included (median age, 41 (range, 18-81) years) of whom 514 were premenopausal and 152 were postmenopausal. Based on the three-step strategy, 362 women had surgical removal of the mass (53 malignant and 309 benign), 71 masses resolved spontaneously and 233 persisted. Four hundred and forty-eight (67.3%) of 666 masses could be classified using simple descriptors and, of the 218 that could not, 147 (67.4%) were classified using simple rules. Of the remaining 71 masses, the expert examiner classified 45 as benign, 12 as malignant and 14 as uncertain. Overall sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of the three-step strategy were 94.3%, 94.9%, 18.6 and 0.06, respectively. CONCLUSION: The IOTA three-step strategy, based on the sequential use of simple descriptors, simple rules and expert evaluation, performs well for classifying adnexal masses as benign or malignant. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Performance of three-dimensional power Doppler angiography as third-step assessment in differential diagnosis of adnexal masses.

OBJECTIVE: To evaluate the contribution of three-dimensional (3D) power Doppler angiography (3D-PDA) to the differential diagnosis of adnexal masses. METHODS: This was a prospective study in women diagnosed with a persistent adnexal mass and subsequently scheduled for surgery in a tertiary university hospital. All women were evaluated by transvaginal/transrectal ultrasound according to a predetermined three-step protocol, with transabdominal ultrasound being performed in some cases. First, morphological evaluation of the mass was performed using gray-scale 'pattern recognition' (first step). Lesions diagnosed as having a benign pattern were considered as being at low risk of malignancy whereas tumors with solid components, ascites and/or signs of carcinomatosis were considered as being at high risk of malignancy. In both cases no further test was performed and a decision regarding clinical management, either for follow-up or surgery, was taken. Tumors with solid components but without signs of ascites or carcinomatosis were considered as being at intermediate risk of malignancy. These lesions were assessed by two-dimensional (2D) PDA to evaluate tumor vascularity (color score) (second step). Solid tumors with a color score of 1 or 2 were considered as benign and no further test was performed, while tumors with a color score of 2, 3 or 4 within solid components or a color score of 3 or 4 in the case of a solid tumor were considered as malignant. The latter group underwent 3D-PDA assessment (third step). Vascularization index (VI) was calculated in a 1-mL sphere of the most vascularized area of the tumor. When a VI ≥ 24.015% was found, the tumor was considered as malignant. All masses were removed surgically and definitive histological diagnosis was used as the gold standard. Sensitivity and specificity for each strategy were calculated and compared. In the case of bilateral tumors, only the more suspicious one was used for analysis. RESULTS: A total of 367 adnexal masses diagnosed in 367 women (mean age, 46.5 (range, 18-80) years) were evaluated during the study period. Of these, 86 masses were malignant and 281 were benign. The sensitivity and specificity for each assessment strategy were as follows: one-step, 97.7% and 78.6%; two-step, 94.2% and 97.9% (P < 0.001 for specificity when compared with that of one-step); three-step, 90.7% and 98.9% (not statistically significant when compared with that of two-step). CONCLUSIONS: The addition of 2D-PDA in the differential diagnosis of an adnexal mass significantly increases specificity while sensitivity remains high; however performing subsequent 3D-PDA does not provide additional information or further improve diagnostic performance subsequent to 2D-PDA.

Transvaginal color Doppler ultrasonography and CA-125 in suspicious adnexal masses.

OBJECTIVE: To compare diagnostic performance of color Doppler ultrasound and CA-125 in suspicious adnexal masses on B-mode sonography. MATERIALS AND METHODS: Data on 94 patients (mean age: 47.4 years, range: 17-79 years. Fifty-two (55.3%) premenopausal and 42 (44.7%) postmenopausal women) managed in our institution because of a suspicious adnexal mass were reviewed. All patients were evaluated by transvaginal color Doppler ultrasonography (CD) and serum CA-125 level determination prior to surgery. Definitive histopathological diagnosis was obtained in each case. Sonographic morphology evaluation was suspicious in all cases. CD was considered as suspicious when flow was detected and the lowest RI found was < or = 0.45. CA-125 cut-off was > or = 35 UI/ml. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each method and compared. ROC analysis was performed for RI and CA-125. Areas under curve (AUC) were calculated and compared. RESULTS: Fifty-six (59.6%) tumors were found to be malignant and 38 (40.4%) benign. Sensitivity, specificity, PPV and NPV for CD were 87.5% (95% CIs: 75.3-94.4), 84.2% (95% CIs: 68.7-94), 89.1% (95% CIs: 77.7-95.9) and 82.1% (95% CIs: 66.5-92.5), respectively. Sensitivity, specificity, PPV and NPV for CA-125 were 83.9% (95% CIs: 71.7-92.4), 68.4% (95% CIs: 51.3-82.5), 79.7% (95% CIs: 66.2-89) and 74.3% (95% CIs: 56.7-87.5), respectively. Sensitivity, PPV and NPV were not statistically different. CD had higher specificity (P = 0.01). AUC curve for Doppler (0.75) was significantly higher than for CA-125 (0.61) (P = 0.0002). CONCLUSIONS: Our results indicate that color Doppler ultrasound has a better diagnostic performance as compared with CA-125, being significantly more specific.

Saline infusion sonohysterography in endometrial cancer: assessment of malignant cells dissemination risk.

BACKGROUND: To assess the risk of malignant cells dissemination in patients with endometrial cancer undergoing saline infusion sonohysterography (SIS). METHODS: Fourteen consecutive patients (mean age: 58.1 years, range: 41-74 years) diagnosed as having a clinical stage I endometrial carcinoma and scheduled for surgical staging were entered in this study. SIS was performed at the time of laparotomy just when the abdomen was opened and prior to the start of the surgical procedure. 10-20 mL of saline was infused. All fluid spilled from the fimbrial ends of the fallopian tubes was collected and analyzed for the presence or absence of malignant endometrial cells. Samplings were also taken from ascites, if found, or cytological washings, prior to and after SIS. RESULTS: SIS could be satisfactorily performed in all patients. There was no spillage from either tube in nine patients. Mean fluid volume obtained from the other five patients was 4.4 mL. Cytologic analysis revealed the presence of malignant cells in the spilled fluid in one case (7.1%, one out of fourteen). CONCLUSIONS: Our data show that a small but real risk of malignant cell dissemination exists in patients with endometrial carcinoma who undergo SIS.

Transvaginal color Doppler sonography in adnexal masses: which parameter performs best?

The aim of this study was to establish which of several commonly used parameters performs best in the evaluation of adnexal masses by transvaginal color Doppler sonography. A total of 79 adnexal masses in 73 consecutive patients were included in the study. There were 43 (58.9%) premenopausal and 30 (41.1%) postmenopausal patients. The median age was 45 years (range 20-78 years). The parameters compared were: number of vessels detected in each tumor, tumor vessel location (central vs. peripheral), peak systolic velocity (PSV), lowest resistance index (RIlowest), mean resistance index (RImean), lowest pulsatility index (PIlowest) and mean pulsatility index (PImean). Receiver operating characteristic (ROC) curves were plotted to analyze the test performance of the parameters, except for tumor vessel location, and to estimate the best cut-off value of the parameters studied to differentiate between malignant and benign tumors. Definitive histopathological diagnosis was obtained in every case and used as the 'gold standard'. There were 20 (25.3%) malignant and 59 (74.7%) benign masses. Color Doppler signals were detected in 100% of the malignant masses (20 out of 20) and 74.6% (44 out of 59) of the benign masses, and the difference was found to be statistically significant (p < 0.001). Tumor vessel location was central in 18 out of 20 (90%) malignant masses, whereas it was peripheral in 39 out of 44 (88.6%) benign masses. ROC analysis showed that the best cut-off values for number of vessels, PSV, RIlowest, RImean, PIlowest and PImean were three vessels, 25 cm/s, 0.45, 0.55, 0.90 and 1.50, respectively. However, for all these parameters except RIlowest, there was a considerable overlap between benign and malignant tumors, with a high false-positive rate. In conclusion, in our experience, the parameters that performed best were the RIlowest with a cut-off value of 0.45 (sensitivity 100%; false-positive rate 11.4%) and central tumor vessel location (sensitivity 90%; false-positive rate 11.4%).

Blood flow in functional cysts and benign ovarian neoplasms in premenopausal women.

To assess the value of transvaginal color Doppler sonography in the differentiation of functional cysts from benign ovarian neoplasms in premenopausal women, 100 premenopausal women with the diagnosis of adnexal mass were enrolled in a prospective study. All patients underwent transvaginal color Doppler sonography during the follicular phase. We evaluated 107 masses. Tumor volume and morphology were assessed, as were tumor blood flow location, the number of vessels, the resistive and pulsatility indices, and the peak systolic velocity. Patients were followed up after 8 to 10 weeks by transvaginal sonography. Functional cysts were considered when spontaneous resolution occurred. Surgery was performed if a tumor enlarged or persisted after two scans. Thirty-nine (36.5%) cysts regressed spontaneously and 68 (63.5%) were removed surgically. Seven of the latter were follicular or luteal cysts and were considered to be functional cysts. No carcinoma was found. Arterial blood flow was detected in 28 (60.8%) functional cysts and in 42 (68.8%) benign neoplasms (P = 0.3446). The vessels were located peripherally in 27 (94.6%) functional cysts and in 37 (88.1%) benign neoplasms (P = 0.2226). No differences were found between functional cysts and benign neoplasms in mean resistive index (0.65, 95% confidence interval: 0.59 to 0.71 versus 0.64, 95% confidence interval: 0.60 to 0.69), mean pulsatility index (1.47, 95% confidence interval: 1.17 to 1.84 versus 1.57, 95% confidence interval: 1.26 to 1.86), number of vessels (1.1, 95% confidence interval: 0.7 to 1.3 versus 1.4, 95% confidence interval: 1.1 to 1.8), and peak systolic velocity (28.6 cm/s, 95% confidence interval: 24.7 to 34.2 versus 24.9 cm/s, 95% confidence interval: 21.6 to 28.3). We concluded that transvaginal color Doppler sonography is not useful to discriminate between functional ovarian cysts and benign ovarian neoplasms in premenopausal women.

Assessment of a new logistic model in the preoperative evaluation of adnexal masses.

OBJECTIVE: To assess a new logistic regression model developed to predict malignancy in adnexal masses. METHODS: In the first part of this study, we developed a logistic model by applying logistic regression analysis in a series of 268 adnexal masses (203 benign and 65 malignant lesions) in 248 patients (mean age, 43.6 years; SD, 14.2 years) evaluated and treated at our institution. Eleven parameters were entered in the logistic regression analysis in a forward stepwise way. In the second part of the study, we evaluated the model's diagnostic performance in a further set of 135 adnexal masses (103 benign and 32 malignant tumors) in 129 patients (mean age, 44.4 years; SD, 14.6 years). This diagnostic performance was compared with that of age, tumor volume, Sassone's and Ferrazzi's B-mode ultrasonographic morphologic scoring systems, serum cancer antigen 125 level, and the tumor's lowest resistive index. Comparison was done by calculating the area under the receiver operating characteristic curve. RESULTS: In logistic analysis, only menopausal status, the presence of papillary projections, the logarithm of the cancer antigen 125 value, tumor blood flow location, and the lowest resistive index were retained in the model. The model had the best area under the curve (0.97), significantly higher than patient age (area under the curve, 0.78; P = .001), tumor volume (area under the curve, 0.68; P < .0001), cancer antigen 125 (area under the curve, 0.88; P = .008), lowest resistive index (area under the curve, 0.85; P = .011), Ferrazzi's scoring system (area under the curve, 0.89; P = .01), and maximal peak systolic velocity (area under the curve, 0.71; P< .0001). Comparison with Sassone's scoring system (area under the curve, 0.91) did not reach statistical significance, but a clear trend was found (P = .116). CONCLUSIONS: The model had the best diagnostic performance for discriminating between benign and malignant adnexal masses. A clinical prospective evaluation is needed to confirm its actual value.

Comparison of conventional color Doppler imaging and power doppler imaging for the diagnosis of ovarian cancer: results of a European study.

OBJECTIVE: The purpose of this prospective study was to compare the diagnostic accuracy of conventional color Doppler (CCD) imaging and power Doppler (PD) imaging in the diagnosis of ovarian cancer. METHODS: Six hundred fifty-six consecutive women with adnexal masses scheduled for surgery in two European university departments of obstetrics and gynecology underwent preoperative transvaginal ultrasound. The scanning procedure was the same in the two institutions: after B-mode sonography, a CCD/PD imaging scan was performed before pulsed Doppler evaluation. Using both modalities of color Doppler, malignancy was suspected when arterial flow was visualized in an echogenic portion defined as malignant by B-mode. To avoid the risk of bias due to the absence of blindness of the examiner after the first Doppler evaluation, at one institution 328 consecutive women with an adnexal mass were evaluated using only CCD imaging, whereas at the second institution the ultrasonographic evaluation of the same number of masses was performed using PD imaging, and the results were compared prospectively. RESULTS: The age, the rate of postmenopausal women, and the rate of ovarian cancer were similar in the two institutions. The false-positive rate of B-mode imaging was similar in the two institutions (17 versus 18%), while the false-positive rates of CCD and PD imaging were 4.6 and 7.4%, respectively. Although the overall diagnostic accuracy of two techniques seems comparable, with a similar value of K (0.81 versus 0.84), a significantly lower sensitivity in differentiation of benign from malignant ovarian lesions was found using CCD (87 versus 100%). CONCLUSIONS: At least one of the two Doppler techniques should be used in conjunction with B-mode imaging in order to decrease the false-positive rate of B-mode used alone but CCD imaging showed a higher false-negative rate.

Sonographic features of ovarian cystadenofibromas: spectrum of findings.

OBJECTIVE: To describe the sonographic characteristics of ovarian cystadenofibromas. METHODS: We conducted a retrospective study of 23 ovarian tumors histopathologically confirmed as ovarian cystadenofibromas that were preoperatively evaluated by transvaginal color Doppler sonography. RESULTS: In all cases the mass was predominantly cystic. Septations appeared in 30.4% of the tumors. Papillary projections or solid nodules appeared in 56.5% of the cases. The most frequent appearance was a unilocular complex cystic mass. In 47.8% of the tumors, vascularization was detected, having a typical pattern of peripheral vascularization with scattered vessels of high blood flow impedance. CONCLUSIONS: We have described the sonographic spectrum of findings of ovarian cystadenofibromas. The most frequent appearance was a unilocular cystic mass with gross papillary projections or solid nodules. In almost half of the tumors, vascularization could be detected.

Clip placement facilitating the approach to breast lesions.

We describe a novel technique for marking non-palpable breast lesions with the aim of selecting the best approach prior to performing a biopsy. The technique employs a new coil, specifically designed for breast localization, guided by stereotaxy. This technique is reserved for selected cases in which the lesion is seen peripherally in only one mammographic view with negative or non-conclusive ultrasonographic results, and deeply seated after a stereotactic study. Once the coil is released beside the lesion, the shortest approach from the skin may be employed to perform the biopsy. To our knowledge, this is the first report of this technique.

An experience with the Advanced Breast Biopsy Instrumentation (ABBI) system in the management of non-palpable breast lesions.

Our objective was to evaluate our experience with the Advanced Breast Biopsy Instrumentation system (ABBI) in non-palpable breast lesions in a prospective study from July 1998 to November 2000. The ABBI system was included in a protocol for BIRADS 4 non-palpable, small (<15 mm) breast lesions. Digital radiographs of both specimen and biopsy cavity were obtained to validate the procedure. A total of 255 ABBI biopsies were performed in 254 patients. In 251 cases the lesions were successfully removed (98.4%). Mammographic lesions consisted of 176 cases of microcalcifications (69%), 51 cases of architectural distortions (20%) and 28 cases of nodules (11%). Seventy-two carcinomas were diagnosed (28.2%). Affected margins were found in 41 cases (56.9%). Residual tumour was seen in 31 patients (43%). Seventeen borderline results and 33 benign architectural distortions obviated further procedures. The complication rate in 10 cases was as follows: 3 wound infections; 4 haematomas; and 3 vasovagal reactions. The main utility of the ABBI system is to allow a reliable diagnosis in complex lesions, such as small clusters of microcalcifications and especially architectural distortions. Surgery can be avoided for borderline cases if the lesion is completely removed and free margins are obtained in the pathology study. Therapeutic use is controversial and can be applied only in selected cases.