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Revista Peruana de Ginecología y Obstetricia

On-line version ISSN 2304-5132

Rev. peru. ginecol. obstet. vol.66 no.3 Lima Jul-Sep 2020

http://dx.doi.org/10.31403/rpgo.v66i2262 

Original Articles

Validation of IOTA simple ultrasound rules in clinical practice with tumor markers and pathology

Anna Vilà Famada1 

Silvia Pina Pérez1  2 

Judith Jurado Seguer1 

Judith Lleberia Juanos1  2 

Jordi Costa Pueyo1  2 

1 Adjunt Physician Gynecology and Obstetrics Service, Hospital Universitari Parc Taulí. Parc Taulí I3PT Innovation and Research Institute, Universidad Autónoma de Barcelona, Sabadell (08208), Spain

2 Associate Professor Universitat Autónoma de Barcelona (UAB), Hospital Universitari Parc Taulí, Sabadell (08208), Spain

ABSTRACT

Objectives: To determine correlation between preoperative ultrasound evaluation of adnexal masses applying IOTA simple rules and pathology diagnosis. To assess usefulness of biochemical tumor markers in these cases. Methods: A prospective study was performed between January 2017 and February 2020. Patients with suspected ovarian pathology were evaluated using IOTA ultrasound rules and designated as benign or malignant. Findings were correlated with histopathological findings. Collected data was statistically analyzed using the chi-square test and kappa statistical method. Results: During this period, 102 women were eligible for the study. According to IOTA ultrasound criteria, 48% of the adnexal masses were classified as benign, 24.5% malignant and 27.5% were not classifiable. Pathology confirmed 68.1% of benign and 72.8% of malignant tumors were correctly classified by ultrasound. Statistically, the agreement between pre-surgical transvaginal ultrasound and pathology result was significant with contingency coefficient 0.58 and Kappa index 0.47, both with p <0.05 significance. The sensitivity for detection of malignancy with IOTA simple rules was 94.1% and specificity 92.1%. As for biochemical tumor markers, human epididymal protein 4 (HE4) and cancer antigen 125 (CA 125) values had statistically significant correlation with pathology results. Conclusions: IOTA simple rules may be used in clinical practice for diagnosis of ovarian tumors. Human epididymis 4 appeared a better diagnostic tool than CA 125 in discrimination of malignant adnexal masses.

Key words: Ovarian cysts; Ovarian neoplasms; Ultrasonography; Biomarkers; tumor

Introduction

Adnexal masses are a frequent reason for consultation in gynecology and morphological evaluation using pelvic ultrasound is the first study to be performed. An ultrasound is an easily executable, repeatable, relatively low-cost procedure, and remains the method of choice for distinguishing between benign and malignant adnexal pathologies. By identifying patterns, several types of tumors can be classified according to their characteristic appearance in grayscale images. Proper characterization of adnexal masses is a critical step in planning the right therapeutic approach.

Different studies report that up to 90% of ovarian masses can() be correctly classified as benign or possibly malignant by an expert sonographer, and thus determine the need for surgery, the type of surgical procedure and its priority.

Several risk-prediction models have been() proposed, to() differentiate adnexal masses, which evaluate tumors and classify risk according to the following ultrasound findings: multilocularity, presence of solid areas, bi-laterality, ascites, evidence of metastasis, menopausal status and different biochemical markers. Such models can be complex and difficult to apply in standard clinical practice. Several working groups arose from these complexities, such as the International Ovarian Tumor Analysis IIOTA)4-6, which was validated prospectively and externally. This group’s aim was to reach an agreement in relation to ultrasound examinations and its terminology. This consensus of the IOTA group describes the ultrasound characteristics of adnexal tumors and estimates the possible risk of malignancy, in order to create standardized terms and definitions. The main aim is to help less experienced sonographers reproduce the good results of expert sonographers. In addition, the combination of the ultrasound study with biochemical markers (CA125 or HE4) seems to be even more sensitive to classifying the malignance of the lesion7-9.

Our study aimed to assess the clinical applicability of the IOTA model, based on simple ultrasound criteria of classification of adnexal masses in terms of benignity or malignancy, prior to surgical intervention, as well as determining the sensitivity and specificity of said ultrasound assessment and the impact of biochemical markers on decision-making.

Methods

A prospective observational study was carried out in the Ultrasound Unit of the Hospital Universitari Parc Taulí de Sabadell, which included a total of 102 patients with ultrasound diagnosis of adnexal tumors, to which the IOTA criteria were applied and that were surgically intervened between January 2017 and February 2020.

The methodology of the IOTA criteria includes the division of ultrasound findings into two characteristics groups: rules B and rules M (Figure 1). The B rules for predicting a benign tumor consist of the following characteristics: unilocular masses, presence of solid components with a diameter larger than <7 mm, presence of acoustic shadow, multilocular smooth tumor with a diameter larger than <100 mm and no blood flow. M rules for predicting malignant lesion include irregular solid tumor, presence of ascites, at least four papillary structures, irregular multilocular solid tumor with a diameter larger than 100 mm, and an abundant blood flow. If one or more M-rules are applied in the absence of a rule B, a mass is predicted as malignant. If one or more B-rules apply in the absence of an M rule, a mass is predicted as benign. If rules M and rules B apply or no rule applies, the mass is classified as inconclusive.

Figure 1 Iota ultrasound criteria. 

Thus, the adnexal tumors were classified as probably malignant, probably benign or unclassified following the simple rules of IOTA.

The ultrasound study was always with transvaginal access. In cases of tumors with IOTA criteria of malignancy, they were given an additional abdominal study to rule out possible ascites and to finish filing the adnexal mass. In none of these cases this additional abdominal study changed the initially performed transvaginal IOTA assessment. All ultrasound examinations were performed using a Voluson S8 ultrasound equipped with a 5-7.5 MHz endovaginal probe and a 3.5-5 MHz multifrequency convex transabdominal probe. The lesions were classified as solid or liquid, unilocular or multilocular. After evaluation in mode B, Doppler was activated to evaluate tumor vascularity. The Doppler conFiguration was adjusted to achieve maximum sensitivity (frequency 5 MHz; dynamic range 20 to 40 dB; pulse repeat frequency 0.6 kHz). Central vascularity was defined in the presence of color spots within suspicious areas of the tumor such as thick papillary projections, solid areas or central part of solid tumors. Subsequently, presurgical IOTA staging was compared with histopathological results of the surgical specimens.

The four sonographers involved in this study performed all scans, with the informed consent of the patients.

The data was collected through the Microsoft Office Access 2000 program and previously analyzed using SPSS Statistics 17.0. The categorical variables were analyzed using Fisher's test and the chi-square test. The comparison of quantitative variables was performed with the t-student test. Statistical significance was defined as p<0.05. The main study variable was the concordance between the assessment of transvaginal ultrasound using the IOTA criteria and the definitive pathology result, analyzed using the contingency coefficient and the Kappa index.

Results

A total of 102 patients were included in this study. The average age in cases of benignity was 47.6 years and in cases of malignancy, 59 years, difference statistically significant. More than half of these patients (53.9%) were premenopausal.

The location of the tumor was one-sided in 94.1% of cases, 54.9% right and 39.2% left. In 6 cases it was bilateral (5.9%). 72.5% of the masses were regular, 66.7% unilocular, 12.7% bilocular and the remaining 20.6% multilocular.

In most patients, the first symptom was pain (52%), 26.5% of tumors were asymptomatic and 9.8% presented abdominal bloating as an initial symptom (Figure 2).

Figure 2 Clinic OF The adnexal tumor studied. 

Based on the IOTA guidelines, 48% of adnexal masses were classified as benign lesions, 24.5% as malignant and 27.5% unclassifiable.

Biochemical tumor markers were also analyzed. We requested human epididymis protein 4 (HE4) in 57.8% of patients, cancer antigen 125 (CA 125) in 88.2% and carbohydrate antigen 19-9 (CA 19.9) in 73.5% of cases.

Other imaging tests, such as CT in 38.2% of patients and MRI in 16.9%, were needed. Surgical intervention was 98+/-11.9 days from the date of the ultrasound, unlike malignant tumors at 44.7+/-8.4 days, or borderline tumors at 45.1+/-16.9 days.

Out of the 102 adnexal tumors intervened, pathology reported 69 benign tumors, 22 neoplasms and 11 borderline tumors (Figure 3).

Figure 3 Pathologic diagnosis OF adnexal tumors. 

We observed a statistically significant relationship between pre-surgical transvaginal ultrasound and pathological anatomy (Figure 4), with a contingency coefficient of 0.58 and a kappa index of 0.47 (p<0.05). 68.1% of benign masses reported by pathology were described as benign on ultrasound. Of the ovarian neoplasms, 72.8% were described as malignant on ultrasound. Finally, 45.5% of borderline tumors were listed as unclassified on ultrasound. Ultrasound sensitivity turned out to be 94.1% and specificity 92.1%, with a positive likelihood ratio 12 and a negative 0.06. Also, the positive predictive value was 80% and the negative value was 97.9%.

Figure 4 Correlation between transvaginal ultrasound evaluation by iota criteria And pathology final results. 

Regarding biochemical tumor markers, human epididymis protein 4 (HE4) was studied in 59 patients (Figure 5). There were 10.1%% false negatives (6/59) and 5% false positives (3/59), showing statistically significant relation with pathology findings and general contingency coefficient of 0.54, statistically significant. The contingency coefficient was not significant in the premenopausal group, 0.40, but statistically significant, 0.6, in the menopausal group.

Figure 5 Correlation between tumor markers And pathology. 

Cancer antigen 125 (Ca 125) was studied in 90 patients (Figure 5). There were 5.5% false negatives (5/90) and 10% false positives (9/90), with statistically significant relationship with pathology and general contingency coefficient of 0.49, statistically significant. In the premenopausal group, a non-significant contingency coefficient of 0,39 was observed, whereas a statistically significant contingency coefficient of 0.52 was obtained in menopausal patients.

Finally, the carbohydrate antigen 19-9 (Ca 19.9) was studied in 75 patients, with results not statistically significant for valuation of adnexal masses (Figure 5).

Discussion

In studies published previously, the simple ultrasound IOTA rules were not applied directly during the ultrasound exam. The ultrasound data was collected subsequently from the patients and evaluated according to prediction models10-14. Our study overcomes this limitation by directly applying simple IOTA ultrasound rules in patients. The literature describes the non-application of the IOTA (non-classifiable IOTA) criteria in about 10% of adnexal tumors. However, this percentage is higher in our case, since we have classified up to 27.5% of ultrasounds as IOTA unclassifiable. However, in most of these cases (64.3%), the definitive pathology was compatible with benignity. This is the main reason why 27% of ovarian neoplasms and 32% of benign tumors were not respectively catalogued as malign or benign, by ultrasound. This limitation arises from the application of a study in usual clinical practice, since not all masses show clearly predictive characteristics of benignity or malignancy.

Despite this comment, we consider that the ultrasound classification of adnexal tumors using IOTA criteria has proven to be highly sensitive and specific to predict ovarian malignancy prior to the surgery of the patient and, in general, prior to the design of a therapeutic strategy. Sensitivity, specificity, positive and negative likelihood ratio have been achieved, as well as positive and negative predictive value very similar to those described in the literature15-17 obtaining good concordance between this test and pathology.

As for the usefulness of biochemical tumor markers for the affiliation of adnexal masses, He4 has recently been proposed as an emerging biomarker in the differential diagnosis of adnexal masses and the early diagnosis of ovarian cancer(18-21). We have individually analyzed each of the biochemical markers in each patient, also considering their age group. In this way we have concluded that both protein He4 and antigen Ca 125 have been useful in the assessment of adnexal tumors, providing more information in menopausal patients. He4 has been shown to be the most useful tumor marker, while Ca 19.9 did not provide additional information for handling of adnexal masses.

The limitation of this study is that of usual clinical practice, where the evaluation of non-classifiable masses using simple rules has been a challenge for researchers. More prospective and preferably randomized studies are needed to establish promising diagnostic tools, such as IOTA, with a positive influence for clinical management of the patient.

We conclude that most adnexal tumors may be correctly classified as benign or malignant using the IOTA classification. Tumor markers, mainly HE4 and also Ca 125, are useful in the preoperative diagnosis of ovarian malignancy, especially in menopausal women.

Acknowledgments

To the service of Gynecology and Obstetrics, especially to the Ultrasound Unit of the Hospital Universitari Parc Taulí de Sabadell, for the follow-up of patients and the realization and notification of the IOTA criteria in all gynecological ultrasounds of adnexal masses.

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4The manuscript was remitted exclusively to the Revista Peruana de Ginecología y Obstetricia. It is not being considered in any other publication and it has not been previously published The authors are responsible for the investigation and have participated in its concept, design, analysis and interpretation of thedata,writingandeditingofthemanuscript, as in the definite approved version which has been sent The authors affirm they got the consent of the institution and of the objects of the study through a specific informed consent form. The project has been authorized by the Ethics Committee of the Hospital Ethical aspects There are no ethical conflicts. This study does not identify the individual, guaranteeing the confidentiality of their data. The data is dissociated in order to collect it in a totally anonymous way. Investigators declare no conflicts of interest. Researchers state that there has been no financial benefit from the promoter or any external entity in connection with the study conducted.

6Citar como: Vilà Famada A, Pina Pérez S, Jurado Seguer J, Lleberia Juanos J, Costa Pueyo J. Validation of IOTA ultrasound criteria in clinical practice with tumor markers and pathology. Rev Peru Ginecol Obstet. 2020;66(3). DOI: https://doi.org/10.31403/rpgo.v66i2262

Received: April 29, 2020; Accepted: May 11, 2020

The authors notify no conflict of interests in relation to their manuscript

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