Diagnostic performance of CA 125, HE4, and risk of Ovarian Malignancy Algorithm for ovarian cancer

AbstractEpithelial ovarian cancer has become the most frequent cause of deaths among gynecologic malignancies. Our study elucidates the diagnostic performance of Risk of Ovarian Malignancy Algorithm (ROMA), Human epididymis secretory protein 4 (HE4) and cancer antigen (CA125). To compare the diagnostic accuracy of ROMA, HE-4 and CA125 in the early diagnosis and screening of Epithelial Ovarian Cancer. Literature search in electronic databases such as Medicine: MEDLINE (through PUBMED interface), EMBASE, Google Scholar, Science Direct and Cochrane library from January 2011 to August 2020. Studies that evaluated the diagnostic measures of ROMA, HE4 and CA125 by using Chemilumincence immunoassay or electrochemiluminescence immunoassay (CLIA or ECLIA) as index tests. Using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). We included 32 studies in our meta-analysis. We calculated AUC by SROC, pooled estimated like sensitivity, specificity, likelihood ratio, diagnostic odds ratio (DOR), Tau square, Cochran Q through random effect analysis and meta-regression. Data was retrieved from 32 studies. The number of studies included for HE4, CA125 and ROMA tests was 25, 26 and 22 respectively. The patients with EOC were taken as cases, and women with benign ovarian mass were taken as control, which was 2233/5682, 2315/5875 and 2281/5068 respectively for the markers or algorithm. The pooled estimates of the markers or algorithm were sensitivity: ROMA (postmenopausal) (0.88, 95% CI 0.86–0.89) > ROMA (premenopausal) 0.80, 95% CI 0.78–0.83 > CA-125(0.84, 95% CI 0.82–0.85) > HE4 (0.73, 95% CI 0.71–0.75) specificity: HE4 (0.90, 95% CI 0.89–0.91) > ROMA (postmenopausal) (0.83, 95% CI 0.81–0.84) > ROMA (premenopausal) (0.80, 95% CI 0.79–0.82) > CA125 (0.73, 95%CI 0.72–0.74), Diagnostic odd’s ratio ROMA (postmenopausal) 44.04, 95% CI 31.27–62.03, ROMA (premenopausal)-18.93, 95% CI 13.04–27.48, CA-125-13.44, 95% CI 9.97–18.13, HE4-41.03, 95% CI 27.96–60.21 AUC(SE): ROMA (postmenopausal) 0.94(0.01), ROMA (premenopausal)-0.88(0.01), HE4 0.91(0.01), CA125-0.86(0.02) through bivariate random effects model considering the heterogeneity. Our study found ROMA as the best marker to differentiate EOC from benign ovarian masses with greater diagnostic accuracy as compared to HE4 and CA125 in postmenopausal women. In premenopausal women, HE4 is a promising predictor of Epithelial ovarian cancer; however, its utilisation requires further exploration. Our study elucidates the diagnostic performance of ROMA, HE4 and CA125 in EOC. ROMA is a promising diagnostic marker of Epithelial ovarian cancers in postmenopausal women, while HE4 is the best diagnostic predictor of EOC in the premenopausal group. Our study had only EOC patients as cases and those with benign ovarian masses as controls. Further, we considered the studies estimated using the markers by the same index test: CLIA or ECLIA. The good number of studies with strict inclusion criteria reduced bias because of the pooling of studies with different analytical methods, especially for HE4. We did not consider the studies published in foreign languages. Since a few studies were available for HE4 and CA125 in the premenopausal and postmenopausal group separately, data were inadequate for sub-group analysis. Further, we did not assess these markers' diagnostic efficiency stratified by the stage and type of tumour due to insufficient studies.

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One-Stop Clinic for Patients with Suspected Ovarian Cancer Pathway from a Retrospective Outcome Study

10.21203/rs.3.rs-42449/v1 ◽

2020 ◽

Author(s):

Ayisha Adeeba Ashmore ◽

C. Gnanachandran ◽

I. Luqman ◽

K. Horrocks

Keyword(s):

Ovarian Cancer ◽

Primary Care ◽

Pelvic Mass ◽

Initial Assessment ◽

Ca 125 ◽

Outcome Study ◽

Ovarian Malignancy ◽

Cancer Symptoms ◽

Nice Guideline ◽

One Stop

Abstract Background:Recent encouragement in early detection of cancer nationally has significantly increased the number of referrals made through the two-week wait suspected cancer pathway. In particular women with abdominal pain and bloating are frequently having their Ca-125 levels investigated for suspected ovarian cancer and this has led to a significant increase in referrals to the ovarian cancer service. We have conducted this study to help improve the efficiency in which these patients are investigated and to improve future pathways within the referral service. Methods:A retrospective observational outcome study. Data were collected from electronic documents of patients’ referrals, assessments, and clinical correspondences.The study was conducted in a tertiary gynaecology cancer centre with primary care direct referrals. The pelvic mass clinic was the clinic setup with consultation, scan and patient support was available. All patients referred by direct primary care for suspected ovarian cancer over two years with Ca-125 result. Data were collected and analysed from the pelvic mass clinic over 48 months, which was available through electronic documentation. Data included information on their consultation, ultrasound scan findings, any further intervention, surgery, and histological outcome of all patient who underwent biopsies or surgery.Results: Two hundred and eighty-six patients were referred from primary care where the NICE guideline, ‘two-week wait for ovarian cancer’, was applied. Two hundred and twenty-three patients were included in this analysis, who had a Ca-125 result reported at the time of their referral. Out of the 223 patients, 126 patients were discharged with or without a repeat Ca-125 after the initial assessment. Seventeen patients were diagnosed with cancer following the referral, but only 12 of them had a primary ovarian malignancy. Conclusion:Majority of the patients with Ca-125 of more than 35U/mL, who were referred through this pathway, did not have cancer. This message can be disseminated by primary care practitioners who may be able to reassure patients prior to their initial consultation with a gynaecologist. This review queries the future value of using Ca-125 as the basis for referrals from primary care referrals for suspected ovarian malignancy. Further studies are required to assess whether a higher Ca-125 cut off may be used as the basis of referrals for postmenopausal women. One-stop focused gynaecology ultrasound clinic (OSFGUC) where clinicians may assess patients with suspected ovarian cancer symptoms and perform ultrasound scans may be better for managing this patient population.

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Preoperative detection of ovarian cancer by color doppler ultrasonography and CA 125

Bangladesh Medical Research Council Bulletin ◽

10.3329/bmrcb.v36i2.6991 ◽

1970 ◽

Vol 36 (2) ◽

pp. 68-73 ◽

Cited By ~ 7

Author(s):

Fawzia Hossain ◽

Md Nazmul Karim ◽

Shah Md Mahfuzur Rahman ◽

Nazreen Khan ◽

Maruf Siddiqui ◽

...

Keyword(s):

Ovarian Cancer ◽

Early Detection ◽

Predictive Value ◽

Ovarian Tumor ◽

Pulsatility Index ◽

Color Doppler ◽

Resistance Index ◽

Ca 125 ◽

Ovarian Malignancy ◽

Age Group

Purpose: Early detection of ovarian malignancy is of great clinical importance. The high mortality rate is due to the difficulties with the early detection of ovarian cancer. Current research attempted to assess the accuracy of Color Doppler Sonography and serum CA-125 level as diagnostic tool of ovarian tumor.Materials and Methods: In this cross-sectional study, 60 consecutive patients with ovarian tumor attending the Department of Obstetrics and Gynecology of BSMMU were recruited. Of the study participants 23.3% belong to 16-25 year age group, 20% belong to 26-35 years age group and 23.30% each were of 46-55 years and > 55 years age group. All the patients recruited were from in-patient department and had undergone surgery. Following excision, routine histopathology revealed 43.30% malignant (n=26) and 56.7% (n=34) benign ovarian lesion. Data were collected from the clinical history form and bimanual pelvic examination, serum CA 125 levels, estimation of Resistance index (RI), Pulsatility Index (PI), Novel Index by CDS and post-operative histo-pathological findings were then recorded. Sensitivity, specificity, accuracy, positive and negative predictive value of the diagnosis made by CDS, CA125, in the discrimination of the benign and malignant ovarian tumors was calculated. Using Receiver operative characteristics analysis the accuracy of RI, PI, CA 125 and Novel Index in the diagnosis of ovarian tumor (benign or malignant) were assessed.Results: With the Cut-off of <.5, Resistance Index is found to be capable of detecting 92% of malignant cases (sensitivity 91.7), and could detect 89% (specificity 88.9) of benign cases correctly which translates in to 90% accuracy in the diagnosis of ovarian tumor. Predictive values for positive (84.6) and negative (94.1) tests were also found to be quite high. Pulsatility index was found to be moderate accuracy (63.3%) with cutoff <1 for malignancy, however low predictive value for a positive test (38.5) questions its use. Both CA-125 and Novel Index showed similar level of sensitivity and specificity. Although Novel Index is derivative of CA125, Novel Index demonstrated better diagnostic accuracy and negative predictive value. The cutoff for CA 125 was mandated as 83.58. With the value the sensitivity is 76.9% and the specificity is 94.1%. RI is found to be more sensitive in detection of positive cases (Malignant) and CA125 is found to be more accurate in detection of negative cases (Benign). However a combination could be tried to make a better detection.Conclusion: Color Doppler ultra-sonography and CA125 excels in different tasks, the study concludes in favor of concurrent use of the methods for improving efficacy and thus early detection of ovarian malignancy. DOI: 10.3329/bmrcb.v36i2.6991Bangladesh Med Res Counc Bull 2010; 36: 68-73

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Diagnostic Performance of Risk of Ovarian Malignancy Algorithm Against CA125 and HE4 in Connection With Ovarian Cancer: A Meta-analysis

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000804 ◽

2016 ◽

Vol 26 (9) ◽

pp. 1586-1593 ◽

Cited By ~ 30

Author(s):

Farshid Dayyani ◽

Steffen Uhlig ◽

Bertrand Colson ◽

Kirsten Simon ◽

Vinzent Rolny ◽

...

Keyword(s):

Ovarian Cancer ◽

Confidence Interval ◽

Late Stage ◽

Diagnostic Performance ◽

Clinical Decision Making ◽

Early Stage ◽

Area Under The Curve ◽

Ovarian Malignancy ◽

Eligibility Criteria ◽

Sensitivity Specificity

ObjectivesThe aim of this study was to determine whether the Risk of Ovarian Malignancy Algorithm (ROMA) is more accurate than the human epididymis 4 (HE4) or carbohydrate antigen 125 (CA125) biomarkers with respect to the differential diagnosis of women with a pelvic mass. The secondary objective is to assess the performance of ROMA in early-stage ovarian cancer (OC) and late-stage OC, as well as premenopausal and postmenopausal patient populations.Methods/MaterialsThe PubMed and Google Scholar databases were searched for relevant clinical studies. Eligibility criteria included comparison of ROMA with both HE4 and CA125 levels in OC (unspecified, epithelial, and borderline ovarian tumors), use of only validated ROMA assays, presentation of area under the curve and sensitivity/specificity data, and results from early-stage OC, late-stage OC and premenopausal and postmenopausal women. Area under the curve (AUC), sensitivity/specificity, and the diagnostic odds ratio (DOR) results were summarized.ResultsFive studies were selected comprising 1975 patients (premenopausal, n = 1033; postmenopausal, n = 925; benign, n = 1387; early stage, n = 192; and late stage, n = 313). On the basis of the AUC (95% confidence interval) data for all patients, ROMA (0.921 [0.855–0.960]) had a numerically greater diagnostic performance than CA125 (0.883 [0.771–0.950]) and HE4 (0.899 [0.835–0.943]). This was also observed in each of the subgroup populations, in particular, the postmenopausal patients and patients with early OC. The sensitivity and specificity (95% confidence interval) results showed ROMA (sensitivity, 0.873 [0.752–0.940]; specificity, 0.855 [0.719–0.932]) to be numerically superior to CA125 (sensitivity, 0.796 [0.663–0.885]; specificity, 0.825 [0.662–0.919]) and HE4 (sensitivity, 0.817 [0.683–0.902]; specificity, 0.851 [0.716–0.928]) in all patients and for the early- and late-stage OC subgroups. Finally, the ROMA log DOR results were better than HE4 and CA125 log DOR results especially for the early-stage patient group.ConclusionsThe results presented support the use of ROMA to improve clinical decision making, most notably in patients with early OC.

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DIAGNOSTIC VALUE OF CA-125 IN PATIENTS WITH EPITHELIAL OVARIAN CANCER AT THE DR. SOETOMO GENERAL HOSPITAL SURABAYA IN 2016

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v25i2.1380 ◽

2019 ◽

Vol 25 (2) ◽

pp. 145

Author(s):

Kintan Putri ◽

Betty Agustina Tambunan ◽

Willy Sandhika

Keyword(s):

Ovarian Cancer ◽

Positive Predictive Value ◽

Epithelial Ovarian Cancer ◽

Tumor Marker ◽

General Hospital ◽

Negative Predictive Value ◽

Predictive Value ◽

Diagnostic Value ◽

Ca 125 ◽

Ovarian Malignancy

Ovarian cancer is the fourth cancer with most incidence in Indonesian female with 10.238 cases in 20141. Tumor marker CA-125 is assosciated with ovarian cancer, importantly epithelial ovarian cancer. This study aims to find out diagnostic value (sensitivity, specificity, positive predictive value, negative predictive value) of CA-125 among patients with epithelial ovarian cancer in Dr. Soetomo General Hospital Surabaya in 2016. This study used analytic cross sectional method and was performed by evaluating medical records of patients suspected for ovarian malignancy in Dr. Soetomo General Hospital Surabaya in 2016. There were total 97 patients found fit for criteria of inclusion in this study. Tissue histopathological examination confirmed 66 patients have epithelial ovarian malignancy and 31 patients do not. Samples distributed using 35 U/ml as CA-125 upper limit, TP: 54.64%, FP: 19.59%, FN: 13.40%, dan TN: 12.37%. Diagnostic value obtained as follows: sensitivity 80.30%, spesificity 38.71%, positive predictive value 73.61%, negative predictive value 48%, and accuracy 67.01%. Tumor marker associated with ovarian cancer CA-125 has found high in sensitivity but low in specificity among patients with epithelial ovarian cancer in Dr. Soetomo General Hospital Surabaya in 2016.

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A Combinatorial Proteomic Biomarker Assay to Detect Ovarian Cancer in Women

Biomarkers in Cancer ◽

10.1177/1179299x18756646 ◽

2018 ◽

Vol 10 ◽

pp. 1179299X1875664 ◽

Cited By ~ 1

Author(s):

Meredith C Henderson ◽

Michael Silver ◽

Sherri Borman ◽

Quynh Tran ◽

Elias Letsios ◽

...

Keyword(s):

Ovarian Cancer ◽

General Population ◽

Clinical Performance ◽

Gynecological Cancer ◽

Area Under The Curve ◽

Ca 125 ◽

Limiting Factor ◽

Ovarian Malignancy ◽

Better Than ◽

Rule Out

Ovarian cancer is often fatal and incidence in the general population is low, underscoring the necessity (and the challenges) for advancements in screening and early detection. The goal of this study was to design a serum-based biomarker panel and corresponding multivariate algorithm that can be used to accurately detect ovarian cancer. A combinatorial protein biomarker assay (CPBA) that uses CA125, HE4, and 3 tumor-associated autoantibodies resulted in an area under the curve of 0.98. The CPBA Ov algorithm was trained using subjects who were suspected to have gynecological cancer and were scheduled for surgery. As a surgical rule-out test, the clinical performance achieves 100% sensitivity and 83.7% specificity. Although sample size (n = 60) is a limiting factor, the CPBA Ov algorithm performed better than either CA-125 alone or the Risk of Ovarian Malignancy Algorithm.

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International Ovarian Tumor Analysis (IOTA) Scoring System to Predict Ovarian Malignancy Preoperatively

Indonesian Journal of Obstetrics and Gynecology ◽

10.32771/inajog.v4i1.71 ◽

2016 ◽

Author(s):

Yuri Feharsal ◽

Andi D Putra

Keyword(s):

Predictive Value ◽

Ovarian Tumor ◽

Diagnostic Performance ◽

Ca 125 ◽

Ovarian Malignancy ◽

Scoring Method ◽

Simple Rules ◽

Histopathology Result ◽

Risk Of Malignancy ◽

Sensitivity Specificity

Objective: To compare diagnostic performance of International Ovarian Tumor Analysis (IOTA) scoring method with Risk of Malignancy Index-4 (RMI-4) and Sassone Morphology Index to predict ovarian malignancy preoperatively. Method: Retrospective study with 119 subject who underwent surgical removal of ovarian tumor and performed histopathological examination at Dr. Cipto Mangunkusumo Hospital on January to December 2013. Demographic status, ultrasound scans, CA-125 level and histopathological result were collected to calculate the score of each method. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated by comparing each score with histopathology result. Comparison of diagnostic performance was analyzed by ROC curve. Result: There were 51.26% subjects with benign tumor and 48.74% subjects with malignant tumor. Result was analyzed with sensitivity test (IOTA simple-rules, IOTA subgroup, RMI-4 and Sassone): 98%, 88%, 86% and 79%; specificity: 74%, 67%, 61% and 89%; positive predictive value: 78%, 72%, 68% and 87%; negative predictive value: 98%, 85%, 82% and 81%; and accuracy: 86%, 77%, 73% and 84%. AUC value for IOTA simple-rules, IOTA subgroup, RMI-4 and Sassone were: 0.86, 0.78, 0.73 and 0.84. Comparison of these results were significant with p = 0.000. Conclusion: IOTA simple-rules had better sensitivity, negative predictive value and accuracy than IOTA subgroup, RMI-4 and Sassone morphology index to predict ovarian malignancy preoperatively. [Indones J Obstet Gynecol 2016; 1: 42-46] Keywords: iota, ovarian neoplasm, risk of malignancy, scoring

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Early-Stage Ovarian Malignancy Score versus Risk of Malignancy Indices: Accuracy and Clinical Utility for Preoperative Diagnosis of Women with Adnexal Masses

Medicina ◽

10.3390/medicina56120702 ◽

2020 ◽

Vol 56 (12) ◽

pp. 702

Author(s):

Phichayut Phinyo ◽

Jayanton Patumanond ◽

Panprapha Saenrungmuaeng ◽

Watcharin Chirdchim ◽

Tanyong Pipanmekaporn ◽

...

Keyword(s):

Ovarian Cancer ◽

Clinical Utility ◽

Early Stage ◽

Ca 125 ◽

Lower Sensitivity ◽

Ovarian Malignancy ◽

Threshold Probability ◽

Adnexal Masses ◽

Risk Of Malignancy ◽

Early Stage Ovarian Cancer

Background and objectives: To compare the diagnostic accuracy and clinical utility of the Early-stage Ovarian Malignancy (EOM) score with the Risk of Malignancy Index (RMI) in the presurgical assessment of women presenting with adnexal masses. Materials and Methods: A secondary analysis was carried out in a retrospective cohort of women who presented with an adnexal mass and were scheduled for surgery at Phrapokklao Hospital between September 2013 and December 2017. The clinical characteristics, ultrasonographic features of the masses, and preoperative CA-125 levels were recorded. The EOM and the RMI score were calculated and compared in terms of accuracy and clinical utility. Decision curve analysis (DCA), which examined the net benefit (NB) of applying the EOM and the RMI in practice at a range of threshold probabilities, was presented. Results: In this study, data from 270 patients were analyzed. Fifty-four (20.0%) women in the sample had early-stage ovarian cancer. All four RMI versions demonstrated a lower sensitivity for the detection of patients with early-stage ovarian cancer compared to an EOM score ≥ 15. An EOM ≥ 15 resulted in a higher proportion of net true positive or NB than all versions of the RMIs from a threshold probability of 5% to 30%. Conclusions: It also showed a higher capability to reduce the number of inappropriate referrals than the RMIs at a threshold probability between 5% and 30%. The EOM score showed higher diagnostic sensitivity and has the potential to be clinically more useful than the RMIs to triage women who present with adnexal masses for referral to oncologic gynecologists. Further external validation is required to support our findings.

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Copenhagen Index versus ROMA in the preoperative ovarian malignancy risk stratification: result from the first Vietnamese prospective cohort study

10.21203/rs.3.rs-366745/v1 ◽

2021 ◽

Author(s):

Doan Tu Tran ◽

Van Khoa Vo ◽

Minh Tam Le ◽

Linus Chuang ◽

Vu Quoc Huy Nguyen

Keyword(s):

Ovarian Cancer ◽

Cohort Study ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Menopausal Status ◽

Ca 125 ◽

Benign Tumors ◽

Ovarian Malignancy ◽

Malignancy Risk ◽

Preoperative Prediction

Abstract Objectives: This study aimed to evaluate the diagnostic performances of the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA) in the preoperative prediction of ovarian cancer.Methods: In a prospective cohort study, data were collected from 475 patients with ovarian masses who were hospitalized at the Departments of Obstetrics and Gynecology, Hue Central Hospital and Hue University of Medicine and Pharmacy Hospital, Vietnam, between January 2018 and June 2020. ROMA and CPH-I were included for the women who had measurements of serum carbohydrate antigen (CA-125) and human epididymis protein (HE4). Matching these values to postoperative histopathology resulted in the preoperative prediction values. The final diagnosis was based on clinical features, histologic, radiologic findings, and the International Federation of Gynecology and Obstetrics (FIGO) 2014 stages of ovarian cancer were recorded.Results: Among the 475 women, 408 had benign tumors, 5 had borderline tumors and 62 had malignant tumors. The two indices showed similar discriminatory performances with no significant differences (p > 0.05). At an optimal cut-off, the sensitivities/specificities of ROMA and CPH-I for ovarian cancer diagnosis were 76.1% and 87.0%, 83.6% and 78.7%, respectively. The optimal cut-off for CPH-I was 1.89%. The areas under the ROC curves (AUCs) of ROMA and CPH-I were 0.860 (95%CI: 0.825 – 0.890) and 0.868 (95%CI: 0.833 – 0.896), respectively.Conclusions: The introduction of the Copenhagen Index to help stratify the malignancy risk of ovarian tumor, irrespective of menopausal status might be applied as a simple alternative with a similar efficacy to ROMA in clinical practice.

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A diagnostic approach for differentiating abdominal tuberculosis from ovarian malignancy: a case series and literature review

BMC Proceedings ◽

10.1186/s12919-019-0180-y ◽

2019 ◽

Vol 13 (S11) ◽

Cited By ~ 1

Author(s):

Moh Nailul Fahmi ◽

Annisaa Pelita Harti

Keyword(s):

Ovarian Cancer ◽

Extrapulmonary Tuberculosis ◽

Clinical Manifestations ◽

Case Series ◽

Abdominal Tuberculosis ◽

Diagnostic Approach ◽

Ca 125 ◽

Imaging Features ◽

Ovarian Malignancy ◽

Cancer Antigen 125

Abstract Background Abdominal tuberculosis is an uncommon variant of extrapulmonary tuberculosis. It accounts for 3.5% of extrapulmonary tuberculosis. Diagnosis of abdominal tuberculosis is still a challenge due to its non-specific symptoms. Abdominal tuberculosis and ovarian cancer may show similar symptoms, laboratory and imaging features. The goal of our report is to emphasize for the need of a diagnostic approach based on clinical manifestations, laboratory, imaging findings, and additional tests for considering a diagnosis of abdominal tuberculosis rather than ovarian cancer. Case presentation We report 3 cases of abdominal tuberculosis in our Onco-gynaecology Division, Department of Obstetrics and Gynaecology, Sardjito Hospital, Yogyakarta, Indonesia in 2018 which were previously diagnosed as ovarian malignancy and managed surgically. All of our patients experienced abdominal pain and enlargement but only two of them had significant weight loss. The general symptoms were typically found in onco-gynaecology patients, especially in those with ovarian malignancy. Ultrasound examination showed multilocular masses, 2 of them with solid parts and ascites. Cancer antigen 125 (CA-125) levels were found increasing in those three patients. All of them were treated surgically and diagnosis of abdominal tuberculosis was established through the histopathological result of tissue biopsy. Based on our cases and literature, we consider the need of a diagnostic approach to differentiate abdominal tuberculosis from ovarian malignancy, an attempt to avoid unnecessary invasive procedures that put burden risk for the patients. Conclusion Minimally invasive tests to establish the diagnosis of abdominal tuberculosis should be optimized to reduce the burden risk of laparotomy. Careful diagnostic steps should be followed to avoid wrong diagnosis.

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