A reflex testing protocol using two multivariate index assays improves the risk assessment for ovarian cancer in patients with an adnexal mass.

OBJECTIVES: Patients with adnexal masses suspicious for malignancy benefit from referral to oncology specialists during presurgical assessment of the mass. OVA1 is a multivariate assay using a five-biomarker panel which offers high overall and early-stage sensitivity. However, OVA1 has a high false-positive rate for benign masses. Overa, a second-generation multivariate index assay was developed to reduce the false-positive rate. The aim of the present study was to use Overa as a reflex for OVA1 and increase specificity. METHODS: OVA1 cut-off scores were established to place patients into three categories: low, intermediate, and high cancer risk. Samples with intermediate-risk OVA1 scores were reflexed to the Overa and defined as high or low risk. This protocol was tested with 1035 prospectively collected serum samples and validated with an independent prospectively collected sample set (N = 207). RESULTS: Thirty-five per cent (359) of samples had intermediate OVA1 scores. Reflexing these to Overa eliminated 58% of the false-positives and improved the overall specificity from 50% to 72%. This finding was confirmed in the independent dataset, in which the specificity increased from 56% to 73%. CONCLUSIONS: Reflexing samples with intermediate OVA1 scores significantly decreases the false-positive rate, thereby reducing unnecessary surgical referrals.

Ultrasound image analysis using deep neural networks for discriminating between benign and malignant ovarian tumors: comparison with expert subjective assessment.

OBJECTIVES: To develop and test the performance of computerized ultrasound image analysis using deep neural networks (DNNs) in discriminating between benign and malignant ovarian tumors and to compare its diagnostic accuracy with that of subjective assessment (SA) by an ultrasound expert. METHODS: We included 3077 (grayscale, n = 1927; power Doppler, n = 1150) ultrasound images from 758 women with ovarian tumors, who were classified prospectively by expert ultrasound examiners according to IOTA (International Ovarian Tumor Analysis) terms and definitions. Histological outcome from surgery (n = 634) or long-term (≥ 3 years) follow-up (n = 124) served as the gold standard. The dataset was split into a training set (n = 508; 314 benign and 194 malignant), a validation set (n = 100; 60 benign and 40 malignant) and a test set (n = 150; 75 benign and 75 malignant). We used transfer learning on three pre-trained DNNs: VGG16, ResNet50 and MobileNet. Each model was trained, and the outputs calibrated, using temperature scaling. An ensemble of the three models was then used to estimate the probability of malignancy based on all images from a given case. The DNN ensemble classified the tumors as benign or malignant (Ovry-Dx1 model); or as benign, inconclusive or malignant (Ovry-Dx2 model). The diagnostic performance of the DNN models, in terms of sensitivity and specificity, was compared to that of SA for classifying ovarian tumors in the test set. RESULTS: At a sensitivity of 96.0%, Ovry-Dx1 had a specificity similar to that of SA (86.7% vs 88.0%; P = 1.0). Ovry-Dx2 had a sensitivity of 97.1% and a specificity of 93.7%, when designating 12.7% of the lesions as inconclusive. By complimenting Ovry-Dx2 with SA in inconclusive cases, the overall sensitivity (96.0%) and specificity (89.3%) were not significantly different from using SA in all cases (P = 1.0). CONCLUSION: Ultrasound image analysis using DNNs can predict ovarian malignancy with a diagnostic accuracy comparable to that of human expert examiners, indicating that these models may have a role in the triage of women with an ovarian tumor. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Análisis de imágenes ecográficas utilizando redes neurales profundas para distinguir entre tumores ováricos benignos y malignos: comparación con la evaluación subjetiva de expertos OBJETIVOS: Desarrollar y probar el desempeño del análisis de imágenes ecográficas computarizadas utilizando redes neurales profundas (RNP) para distinguir entre tumores ováricos benignos y malignos y comparar su precisión en el diagnóstico con la de la evaluación subjetiva (ES) por especialistas expertos en ecografía. MÉTODOS: Se incluyeron 3077 (escala de grises, n=1927; power Doppler, n=1150) imágenes de ultrasonido de 758 mujeres con tumores ováricos, que fueron clasificadas prospectivamente por examinadores especialistas en ecografía, de acuerdo con los términos y definiciones de la IOTA (Análisis Internacional de Tumores Ováricos). El resultado histológico de la cirugía (n=634) o el seguimiento a largo plazo (≥3 años) (n=124) sirvieron como el estándar de referencia. El conjunto de datos se dividió en un subconjunto de formación (n=508; 314 benignos y 194 malignos), un subconjunto de validación (n=100; 60 benignos y 40 malignos) y un subconjunto de pruebas (n=150; 75 benignos y 75 malignos). Se utilizó el aprendizaje de transferencia en tres RNP pre-formadas: VGG16, ResNet50 y MobileNet. Cada modelo fue formado primero mediante escalas de temperatura, al igual que los la calibración de los outputs. A continuación, se utilizó una combinación de los tres modelos para estimar la probabilidad de que el tumor fuera maligno con base en la totalidad de las imágenes de un caso determinado. La combinación de RNP permitió clasificar los tumores como benignos o malignos (modelo Ovry-Dx1); o como benignos, no concluyentes o malignos (modelo Ovry-Dx2). Se comparó el desempeño para el diagnóstico de los modelos de RNP, en términos de sensibilidad y de especificidad, con el de la ES para la clasificación de los tumores ováricos en el subconjunto de formación. RESULTADOS: Con una sensibilidad del 96,0%, Ovry-Dx1 tuvo una especificidad similar a la de la ES (86,7% frente a 88,0%; P=1,0). Ovry-Dx2 tuvo una sensibilidad del 97,1% y una especificidad del 93,7%, y designaron un 12,7% de las lesiones como no concluyentes. Cuando se complementó Ovry-Dx2 con ES en los casos no concluyentes, la sensibilidad general (96,0%) y la especificidad (89,3%) no fueron significativamente diferentes de la utilización de ES en todos los casos (P=1,0). CONCLUSIÓN: El análisis de imágenes ecográficas mediante RNP puede predecir el cáncer de ovario con una precisión en el diagnóstico igual a la de los especialistas expertos humanos, lo que indica que estos modelos pueden jugar un papel en el triaje de mujeres con un tumor de ovario. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Preoperative Risk Stratification of Adnexal Masses in the Pediatric and Adolescent Population: Evaluating the Decision Tree System.

STUDY OBJECTIVE: To evaluate the diagnostic performance of the Decision Tree System (DTS) rules 2 and 3 for surgically managed adnexal masses in the North American population and to compare it with the risk stratification criteria used at The Hospital for Sick Children (≥8 cm and complex/solid). DESIGN: A retrospective cohort study of patients who presented with adnexal masses and were surgically treated between April 2011 and March 2016. SETTING: The Hospital for Sick Children (Toronto, Ontario, Canada). PARTICIPANTS: Patients 1-18 years of age with adnexal masses who underwent surgical treatment. INTERVENTIONS AND MAIN OUTCOME MEASURES: Main outcome measures included diagnostic performance (preoperative sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV] for malignancy) of the DTS rules 2 and 3 and ≥8 cm and complex/solid criteria. RESULTS: The malignancy rate was 10.4%. The DTS rules 2 and 3 had a sensitivity of 84% (95% confidence interval [CI], 79-90), specificity of 77% (95% CI, 71-83), PPV of 30% (95% CI, 17-42), and NPV of 98% (95% CI, 94-100). The 8 cm or larger and complex/solid criteria had a sensitivity of 89% (95% CI, 85-94), specificity of 71% (95% CI, 64-77), PPV of 27% (95% CI, 16-38), and NPV of 98% (95% CI, 96-100). CONCLUSION: Our study showed that DTS rules 2 and 3 had similar diagnostic performance as the 8 cm or larger and complex/solid criteria in the same population, with a very high NPV and a low PPV. Future prospective investigations should be conducted to further assess how DTS components can be incorporated into future algorithms for the management of adnexal masses in the pediatric population.

Risk of Ovarian Malignancy Algorithm versus Risk Malignancy Index-I for Preoperative Assessment of Adnexal Masses: A Systematic Review and Meta-Analysis.

PURPOSE: To perform a systematic review and meta-analysis of studies comparing the diagnostic accuracy of Risk of Ovarian Malignancy Algorithm (ROMA) and risk of malignancy index (RMI) for detecting ovarian cancer. METHODS: A systematic review and meta-analysis was performed according to PRISMA statement. A search for studies evaluating the diagnostic performance of ROMA and RMI-I indices for detecting ovarian malignancy from January 2010 to October 2018 was performed in the PubMed/MEDLINE and Web of Science databases. The quality of the studies was evaluated by the Quality Assessment of Diagnostic Accuracy Studies 2. RESULTS: Sixty-six citations were identified. After exclusions, 8 papers comprising 2,662 women (1,319 premenopausal and 1,343 postmenopausal) were ultimately included. The mean prevalence of ovarian malignancy was 29.0% in premenopausal women and 51.0% in postmenopausal women. High risk of bias for patient selection was observed for most studies. ROMA and RMI-I had a similar diagnostic performance in postmenopausal women (pooled sensitivity [87 vs. 77%] and specificity [75 vs. 85%], respectively. p = 0.29). In premenopausal women, RMI-I showed better specificity than ROMA (89 vs. 78%, p = 0.022) with similar sensitivity (73 vs. 80%, p= 0.27). Significant heterogeneity was found for sensitivity and specificity in comparisons of both groups. CONCLUSIONS: ROMA and RMI-I have similar diagnostic performance for detecting ovarian cancer in women presenting with an adnexal mass. However, RMI-I showed a higher specificity than ROMA in premenopausal women. Notwithstanding, as the risk of bias is high in most studies, our results should be interpreted with caution.

Clinical Performance Comparison of Two In-Vitro Diagnostic Multivariate Index Assays (IVDMIAs) for Presurgical Assessment for Ovarian Cancer Risk.

INTRODUCTION: Adnexal or pelvic mass is a finding that commonly raises suspicion for malignancy, especially for ovarian cancer. Proper identification prior to surgery would permit appropriate referral to a specialty center in cases likely to be ovarian cancer, as optimal outcomes in such cases are obtained when surgical staging and treatment are provided at the time of initial surgery. METHODS: We compared the screening capabilities of two in vitro diagnostic multivariate index assays (IVDMIAs), a new IVDMIA (second-generation multivariate index assay: MIA2G) and a currently used triage algorithm (Risk of Ovarian Malignancy Assay: ROMA). RESULTS: Among 245 subjects (24.7%) determined to have a malignancy, ROMA misclassified 51 malignancies (including 10 high-grade ovarian malignancies), whereas MIA2G misclassified 22 (including 5 high-grade ovarian malignancies). Early stage cancers were more frequently misclassified by ROMA (20 vs. 8 cases). The rate of "test-negative" malignancies was significantly higher for ROMA, while the rate of "test-positive" benign cases was significantly higher for MIA2G. CONCLUSION: Triage algorithms play an important role in improving clinical outcomes for women presenting with an adnexal mass regardless of the eventual diagnosis. In this study, MIA2G was shown to correctly predict more cases of ovarian cancer than the ROMA algorithm. FUNDING: Aspira Labs/Vermillion Inc.

Assessment of the diagnostic value of using serum CA125 and GI-RADS system in the evaluation of adnexal masses.

Cancer antigen 125 (CA125) is a valuable tumor marker for ovarian cancer. Gynecology Imaging Reporting and Data System (GI-RADS) is proved to be effective at identifying the adnexal masses. We investigated whether the combination of these two methods can improve the diagnostic accuracy of ovarian cancer.We retrospectively analyzed preoperative data of 325 patients diagnosed with suspected adnexal mass, 196 patients with benign ovarian masses and 129 with malignant ovarian cancer (stage I: 34, II: 16, III: 61, IV: 18). CA125 was analyzed using the ARCHITECT system, GI-RADS was evaluated according to the International Ovarian Tumor Analysis consensus nomenclature and definitions. Sensitivities and specificities were also calculated for GI-RADS, CA125 and the combinations.The sensitivity, specificity and accuracy of CA125, GI-RADS were 75.97%, 79.59%, 78.15%, and 90.70%, 90.82%,90.77%, the combination data were 94.79%, 96.00%,95.53%. The AUC of combined diagnostic methods was the largest and significantly better compared with each method alone, P < .001). For stage I-II malignancy, GI-RADS as a single method was superior to CA125.Combined use of serum CA 125 and GI-RADS system improved the identification of adnexal masses at high risk of malignancy and could be used for clinical decision-making.

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.

Prolonged Vaginal Bleeding in an Adolescent Secondary to a Foreign Body: Need for a Comprehensive Assessment and Complex Surgery.

BACKGROUND: Heavy, prolonged menstrual bleeding is common in adolescents and results from a variety of etiologies. CASE: A 13-year-old, virginal girl was referred for prolonged, heavy vaginal bleeding despite combined oral contraceptive use and elected management with a levonorgestrel intrauterine device. A preprocedure exam revealed a plastic foreign body embedded in the posterior vaginal fornix, however, attempted removal in the office was unsuccessful. Subsequent computed tomography imaging of the pelvis revealed a vaginal foreign body, complex adnexal mass, and hydroureter. The patient underwent exam under anesthesia and diagnostic laparoscopy, but required conversion to exploratory laparotomy for removal of a foreign body because of vaginal perforation abutting the rectum. SUMMARY AND CONCLUSION: Foreign bodies not easily removed in the outpatient setting should be considered for surgical removal with consideration of preoperative multidisciplinary coordination when imaging reveals intra-abdominal pathology, such as tubo-ovarian abscess and hydroureter.

Diagnostic accuracy and cost-effectiveness of different strategies to triage women with adnexal masses: a prospective study.

OBJECTIVE: Transvaginal sonography (TVS) and serum biomarkers are used widely in clinical practice to triage women with adnexal masses, but the effectiveness of current biomarkers is weak. The aim of this study was to determine the best method of diagnosing patients with adnexal masses, in terms of diagnostic accuracy and economic costs, among four triage strategies: (1) the International Ovarian Tumor Analysis group's simple rules (SR) for interpretation of TVS with subjective assessment (SA) by an experienced ultrasound operator when TVS results are inconclusive (referred to hereafter as SR ± SA), (2) SR ± SA and cancer antigen 125 (CA 125), (3) SR ± SA and human epididymis protein 4 (HE4) and (4) SR ± SA and the risk of malignancy algorithm (ROMA). Our main hypothesis was that the addition of the biomarkers to SR ± SA could improve triaging of these patients in terms of diagnostic accuracy (i.e. malignant vs benign). As secondary analyses, we estimated the cost effectiveness of the four strategies and the diagnostic accuracy of SR ± SA at the study hospitals. METHODS: Between February 2013 and January 2015, 447 consecutive patients who were scheduled for surgery for an adnexal mass at the S. Anna and Mauriziano Hospitals in Turin were enrolled in this multicenter prospective cohort study. Preoperative TVS was performed and preoperative CA 125 and HE4 levels were measured. Pathology reports were used to assess the diagnostic accuracy of the four triage strategies and the cost of each strategy was calculated. RESULTS: A total of 391 patients were included in the analysis: 57% (n = 221) were premenopausal and 43% (n = 170) were postmenopausal. The overall prevalence of malignancy was 21%. SR were conclusive in 89% of patients and thus did not require SA; the overall performance of SR ± SA showed a sensitivity of 82%, specificity of 92% and positive and negative predictive values and positive and negative likelihood ratios of 74%, 95%, 10.5 and 0.19, respectively. In premenopausal women, mean cost among the four triage strategies varied from €36.41 for SR ± SA to €70.12 for SR ± SA + ROMA. The addition of biomarkers to SR ± SA showed no diagnostic advantage compared with SR ± SA alone and was more costly. Among postmenopausal women, mean cost among the four triage strategies varied from €39.52 for SR ± SA to €73.23 for SR ± SA + ROMA. Among these women, SR ± SA + CA 125 and SR ± SA + ROMA had a higher sensitivity (both 92% (95% CI, 85-99%)) than SR ± SA (81% (95% CI, 71-91%)), but SR ± SA had a higher specificity (84% (95% CI, 77-91%)). SR ± SA + CA 125 and SR ± SA + ROMA improved diagnostic accuracy, each diagnosing a third more malignant adnexal masses. In postmenopausal women, compared with SR ± SA alone, SR ± SA + CA 125 showed a net reclassification improvement (NRI) of 28.8% at an extra cost of €13.00, while the extra cost for SR ± SA + ROMA was €33.71, with a comparable gain, in terms of NRI, as that of SR ± SA + CA 125. CONCLUSIONS: In our study sample, SR ± SA seems to be the best strategy to triage women with adnexal masses for surgical management. Among postmenopausal women, SR ± SA + CA 125 increased the NRI at a reasonable extra cost. Our data do not justify the use of HE4 and ROMA in the initial triage of women with adnexal masses. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Histopathological diagnoses of adnexal masses: which parameters are relevant in preoperative assessment?

OBJECTIVE: The aim of the study was to assess which clinical, laboratory and ultrasound characteristics of adnexal masses might predict the histopathological nature of the disease. MATERIALS AND METHODS: The study involved all women treated at the Clinic of Gynecology and Obstetrics Clinical Centre of Serbia for adnexal tumors between July 1, 2010 and December 31, 2011. On admission, detailed anamnestic and laboratory data were obtained, expert ultrasound scan performed and RMI was calculated for all patients. Data were related to histopathological findings and statistically analyzed. RESULTS: The study included 540 women out of which 85 had malignant (seven diagnoses), 435 benign (seven diagnoses) and 20 borderline tumors. All types of malignant and borderline tumors were more frequent in postmenopausal women (p=0.000). Only papillary adenocarcinoma significantly more often produced early metastases (p=0.000). Ascites is a common finding in Krukenberg tumors, granulose cell tumors and papillary adenocarcinomas. There were significant differences between tumor diagnoses regarding the levels of Ca 125 and CEA, erythrocyte sedimentation rate (ESR) and risk of malignancy index (RMI) (p<0.05). No significant differences were found within the group of malignant tumor types regarding the levels of all examined tumor markers, ESR as well as RMI (p>0.05). CONCLUSIONS: In the light of our results, patient age, menopausal status, blood levels of Ca 125, CEA and ESR, as well as calculated RMI, can predict the nature of adnexal masses. Unfortunately none of the examined parameters can accurately determine the exact histopathological diagnosis of the adnexal tumor.

Usefulness of the HE4 biomarker as a second-line test in the assessment of suspicious ovarian tumors.

PURPOSE: The aim of our study was the evaluation of HE4 usefulness as a test in assessment of ovarian tumors which are suspicious and difficult to classify correctly via subjective ultrasound examination. METHODS: In this retrospective cohort study 253 women diagnosed with adnexal masses were examined preoperatively. Suspicious tumors (n = 145) were divided into groups of: "probably benign" (n = 70), "uncertain" (n = 34), and "probably malignant" (n = 41). "Uncertain" tumors were also assessed as "benign" (n = 11) or "malignant" (n = 23). The logistic regression model was performed to analyze if the serum marker improves the prediction of a malignant finding and net reclassification improvement (NRI) was calculated to measure diagnostic improvement. RESULTS: Within the analyzed group 85 (58.6%) benign and 60 (41.4%) malignant tumors were confirmed histopathologically. The comparison of HE4 with subjective ultrasound assessment showed lowered NRI in the entire analyzed group as well as in the groups of tumors classified as "probably benign" or "probably malignant" (NRI = -0.16; P = 0.0139 and NRI = -0.133; P = 0.0489, respectively). The analysis of logistic regression model confirmed that biomarkers do not improve diagnostic accuracy. The difference between areas under ROC for HE4 (0.891) and CA125 (0.902) was not statistically significant (P = 0.760). CONCLUSIONS: After subjective ultrasound assessment, the addition of the second-line test-HE4 as well as CA125 serum level does not improve diagnostic performance. However, HE4 evaluation satisfies the clinical expectations of diagnostic tools for ovarian tumors and, thus, may be useful to less experienced sonographers.

Characterization of malignancy of adnexal lesions using ADC entropy: comparison with mean ADC and qualitative DWI assessment.

PURPOSE: To establish the utility of apparent diffusion coefficient (ADC) entropy in discrimination of benign and malignant adnexal lesions, using histopathology as the reference standard, via comparison of the diagnostic performance of ADC entropy with mean ADC and with visual assessments of adnexal lesions on conventional and diffusion-weighted sequences. MATERIALS AND METHODS: In all, 37 adult female patients with an ovarian mass that was resected between June 2006 and January 2011 were included. Volume-of-interest was drawn to incorporate all lesion voxels on every slice that included the mass on the ADC map, from which whole-lesion mean ADC and ADC entropy were calculated. Two independent radiologists also rated each lesion as benign or malignant based on visual assessment of all sequences. The Mann-Whitney test and logistic regression for correlated data were used to compare performance of mean ADC, ADC entropy, and the visual assessments. RESULTS: No statistically significant difference was observed in mean ADC between benign and malignant adnexal lesions (P = 0.768). ADC entropy was significantly higher in malignant than in benign lesions (P = 0.009). Accuracy was significantly greater for ADC entropy than for mean ADC (0.018). ADC entropy and visual assessment by the less-experienced reader showed similar accuracy (P ≥ 0.204). The more experienced reader's accuracy was significantly greater than that of all other assessments (P ≤ 0.039). CONCLUSION: ADC entropy showed significantly greater accuracy than the more traditional metric of mean ADC for distinguishing benign and malignant adnexal lesions. Although whole-lesion ADC entropy provides a straightforward and objective measurement, its potential benefit decreases with greater reader experience.

D-dimer as a tumor marker in pre-operative assessment of adnexal masses.

OBJECTIVE: To determine the sensitivity, specificity, and predictive value ofserum D-dimer testing in preoperative assessment of adnexal masses. MATERIAL AND METHOD: D-dimer levels were measured pre-operatively in 200 women diagnosed with adnexal masses who underwent surgical treatment at Department of Obstetrics and Gynecology, King Chulalongkorn Memorial Hospital between June 2007 and May 2008. The CA-125 level was also recorded RESULTS: When using cut-off value at 500 ng/ml, D-dimer has 91.8% sensitivity, 71.9% specificity, 58.9% PPV and 95.2% NPV of the tests in differentiating benign from malignant adnexal masses, compared with CA-125, which had 75.4%, 73.0%, 59.7%, and 84.8% respectively (cut-off 65 U/ml). Furthermore, the likelihood ratio to be negative ofD-dimer test is high at 0.11. In patients with epithelial ovarian cancer, D-dimer is increased in 83% of early stage (stage 1) ovarian cancer while only 39% of early stage patients have CA-125 level above cut-off value. CONCLUSION: D-dimer could be a useful test in pre-operative assessment of adnexal masses. In this study D-dimer seems to be better than CA-125 in diferentiating benign from malignant adnexal tumors.

An improved risk of malignancy index in diagnosis of adnexal mass.

BACKGROUND: With the advent of color Doppler flow imaging (CDFI) and technological development of detection of serum tumor markers, new opportunities are presented to the improved risk of malignancy index (RMI) based on Jacobs' research for predicting ovarian malignancy in patients with adnexal masses. METHODS: One hundred and eighty women with an adnexal mass admitted for primary laparotomy were studied. Tumor specific growth factor (TSGF) adjusted ultrasound scores and the results of Doppler blood flow analysis were obtained before the operation. Based on the parameters which had been studied in Jacobs' research, TSGF levels and the findings of color Doppler flow imaging, the risk of malignancy model was redesigned using a binary Logistic regression model. The diagnostic efficacy of the improved risk of malignancy index (improved RMI) was compared with the Jacobs' model RMI by receiver operator characteristic (ROC) curve. RESULTS: The ROC curve showed a higher sensitivity (Mcnamer's test, P < 0.05) in the discrimination between benign and malignant adnexal masses for the improved RMI than the RMI. Compared with the RMI, the improved RMI had an advantage in prediction of ovarian germ cell tumors and granular cell tumor (28.57% vs.71.43%, P < 0.05) and the early stage tumors and borderline tumors (33.33% vs. 66.67%, P < 0.05). CONCLUSION: The predictability of the improved RMI is better than the classic Jacobs' model, especially in diagnosis of the ovarian germ cell tumors and granular cell tumor and other early stage adnexal tumors.

Subjective assessment by ultrasound is superior to the risk of malignancy index (RMI) or the risk of ovarian malignancy algorithm (ROMA) in discriminating benign from malignant adnexal masses.

PURPOSE: The combination of two tumour markers, CA125 and HE4, in the risk of ovarian malignancy assay (ROMA) has been shown to be successful in classifying patients into those who have a high or low risk of epithelial ovarian cancer. In the present study, the diagnostic accuracy of ROMA was assessed and compared to the diagnostic accuracy of the two most widely used ultrasound methods, namely the risk of malignancy index (RMI) and subjective assessment by ultrasound. METHODS: From August, 2005 to March, 2009, 432 women with a pelvic mass who were scheduled to have surgery were enrolled in a single-centre prospective cohort study. A preoperative ultrasound was performed and preoperative CA125 and HE4 serum levels were measured. Once the final surgical pathology reports were obtained, the diagnostic accuracy and performance indices of ROMA, RMI and subjective assessment were calculated. RESULTS: Of the 432 eligible patients, 374 could be analysed. Subjective assessment had the highest area under the receiver operator characteristic curve (AUC) (0.968, 95%CI:0.945-0.984), followed by the RMI (0.931, 95%CI:0.901-0.955). The subjective assessment and RMI both had significantly higher AUCs than the ROMA (0.893, 95%CI:0.857-0.922; P<0.0001 and P=0.0030, respectively). The pre- and postmenopausal populations generated similar results. CONCLUSION: Although new tumour markers models are promising, they do not contribute significantly to the diagnosis of ovarian cancer. Ultrasound, especially subjective assessment by ultrasound, remains superior in discriminating malignant from benign ovarian masses.

Preoperative multimodal strategies for risk assessment of adnexal masses: analysis of 1362 cases in a gynecologic cancer center.

OBJECTIVE: Assessment of adnexal masses focuses on the accurate discrimination between benign and malignant lesions. In our tertiary referral center, we evaluated the discriminative power of expert sonography, serum CA-125 measurement, risk malignancy index (RMI) by Jacobs, and 2 preoperative triage strategies (combination of CA-125 measurement and RMI assessment with expert sonography). METHODS: From 2002 to 2008, a total of 1362 surgical explorations with indication of an adnexal mass from our department were included in this study. Preoperative workup in all patients comprised a gynecologic examination, expert sonography, and serum CA-125 measurement. We calculated sensitivity, specificity, positive and negative predictive value (PPV and NPV), and Cohen κ (prevalence-adjusted measurement) to evaluate the discriminative power of each diagnostic test. RESULTS: Discriminative power of the evaluated tests differed depending on patients' menopausal state. In the premenopause, expert sonography reached the highest discriminative power with a κ value of 0.53, a PPV of 0.45, and an NPV of 0.99. In the postmemopause, the combinations of expert sonography with CA-125 serum measurement or RMI assessment achieved the highest discriminative power: The combination of CA-125 and expert sonography reached a PPV of 0.89 and an NPV of 0.97; κ yielded 0.84. The RMI combined with expert sonography as a triage strategy showed comparable results with a PPV of 0.89, an NPV of 0.96, and a κ value of 0.82. CONCLUSIONS: Preoperative assessment of an adnexal mass may be guided by the patient's menopausal state. In premenopausal patients, expert sonography is helpful for preoperative differentiation between benign and malignant lesions; in postmenopausal patients, the use of triage strategies of either CA-125 serum measurement or RMI combined with expert sonography can be recommended.

Medical devices; ovarian adnexal mass assessment score test system; labeling; black box restrictions. Final rule.

The Food and Drug Administration (FDA) is amending the regulation classifying ovarian adnexal mass assessment score test systems to restrict these devices so that a prescribed warning statement that addresses a risk identified in the special controls guidance document must be in a black box and must appear in all labeling, advertising, and promotional material. The black box warning mitigates the risk to health associated with off-label use as a screening test, stand-alone diagnostic test, or as a test to determine whether or not to proceed with surgery.

Three-dimensional power Doppler vascular network assessment of adnexal masses: intraobserver and interobserver agreement analysis.

OBJECTIVE: The purpose of this study was to assess intraobserver and interobserver agreement for tumor vascular network evaluation as assessed by 3-dimensional (3D) power Doppler sonography for discriminating benign from malignant adnexal masses. METHODS: Stored 3D power Doppler angiographic volume data from 39 women with a diagnosis of a vascularized adnexal mass who were evaluated and treated at our institution were retrieved from our database for analysis. Two different examiners (observer A, with 6 years of experience in 3D sonography; and observer B, with 1 year of experience) reviewed 3D sonograms blinded to each other. Three-dimensional vascular network reconstruction was done with surface rendering in the color mode. Malignancy was considered in the presence of at least 2 of the following: irregular branching, vessel caliber changes, microaneurysms, and vascular lakes. A definitive histologic diagnosis was obtained in all cases. Intraobserver and interobserver agreement rates were estimated by calculating the kappa index. RESULTS: Twenty (51%) tumors were malignant, and 19 (49%) were benign. Intraobserver agreement was good for observer A (kappa = 0.69) and moderate for observer B (kappa = 0.54). Interobserver agreement was moderate (kappa = 0.49). CONCLUSIONS: We found intraobserver and interobserver agreement to be moderate for 3D power Doppler assessment of the vascular network in adnexal masses.

[Laparoscopic assessment following failure to achieve pregnancy after intrauterine inseminations in patients with normal hysterosalpingograms]. / Laparoskopowa ocena zmian w miednicy mniejszej u pacjentek nieplodnych z prawidlowym wynikiem badania HSG.

OBJECTIVES: To assess the diagnostic benefit of laparoscopy in infertile women thought to be at low risk for altered pelvic anatomy. DESIGN: Retrospective chart review. PATIENTS: 127 infertile patients who underwent laparoscopic evaluation of the pelvis failing to conceive after intrauterine inseminations (IUI) with normal hysterosalpingography (HSG). INTERVENTION: Diagnostic and/or therapeutic laparoscopy. MAIN OUTCOME MEASURES: Presence of pelvic pathology and predictors of pelvic disease. RESULTS: Although the hysterosalpingograms were read as normal in all women, endometriosis stage I-II was found in 64 (50,4%) patients, stage III and stage IV in 4 (3,1%). Adhaesions were diagnosed laparoscopically in 22 (17%) patients and distal tubal disease in 26 (20%). All of this abnormalities were directly treated by laparoscopic intervention. The time between HSG and laparoscopy was positively correlated with appearance of distal tubal disease and pelvic adhaesions. CONCLUSION: Laparoscopic findings could lead to a change of treatment decisions in high number of infertile patients with normal hysterosalpingography.