Clinical Significance of the TK1-Specific Activity in the Early Detection of Ovarian Cancer.

INTRODUCTION: Ovarian cancer is the eighth most common cause of cancer death in women. One of the major concerns is almost two-thirds of cases are typically diagnosed in the late stage as the symptoms are unspecific in the early stage of ovarian cancer. It is known that the combination of TK1 protein with CA 125 or HE4 showed better performance than either of them alone. That is why, the aim of the study was to investigate whether the TK1-specific activity (TK1 SA) could function as a complement marker for early-stage diagnosis of ovarian cancer. METHODS: The study included a set of 198 sera consisting of 134 patients with ovarian tumors (72 benign and 62 malignant) and 64 healthy age-matched controls. The TK1 SA was determined using TK1 activity by TK-Liaison and TK1 protein by AroCell TK 210 ELISA. Further, CA 125, HE4, as well as risk of ovarian malignancy algorithm index were also determined in the same set of clinical samples. RESULTS: The TK1 SA was significantly different between healthy compared to ovarian cancer patients (p < 0.0001). Strikingly, TK1 SA has higher sensitivity (55%) compared to other biomarkers in the detection of benign ovarian tumors. Further, the highest sensitivity was achieved by the combination of TK1 SA with CA 125 and HE4 for the detection of benign tumors as well as malignant ovarian tumors (72.2% and 88.7%). In addition, TK1 SA could significantly differentiate FIGO stage I/II from stage III/IV malignancies (p = 0.026). Follow-up of patients after surgery and chemotherapy showed a significant difference compared to TK1 SA at the time of diagnosis. CONCLUSIONS: These results indicate that TK1 SA is a promising blood-based biomarker that could complement CA 125 and HE4 for the detection of early stages of ovarian cancer.

Diagnostic performance of CA125, HE4, ROMA, and CPH-I in identifying primary ovarian cancer.

AIMS: To evaluate the ability of carbohydrate antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA), and Copenhagen Index (CPH-I) to identify primary ovarian cancer (OC) from borderline and benign ovarian tumors (OTs) and explore ideal cutoff points. METHODS: A total of 684 OTs containing 276 OC patients, 116 ovarian borderline OTs and 292 benign OTs patients who underwent surgery in our hospital were included. We retrospectively searched the results of CA125 and HE4 before patients' surgery from the hospital's electronic medical records system. ROMA and CPH-I were calculated according to their menopausal status and age, respectively. Diagnostic performance of these four were assessed by drawing receiver operating characteristic (ROC) curves. RESULTS: CA125, HE4, ROMA, and CPH-I were all significantly higher in OC women compared with borderline OTs (p < 0.001), followed by benign OTs (p < 0.001). Area under the curves (AUCs) for distinguishing OC were 0.850 (0.818-0.882), 0.891 (0.865-0.916), 0.910 (0.888-0.933) and 0.906 (0.882-0.930), respectively, and the corresponding ideal cutoff values for CA125, HE4, ROMA, and CPH-I were 132.5, 68.6, 23.8, and 6.4, respectively. The difference between ROMA and CPH-I was not significant (p = 0.97), but both were higher than CA125 and HE4 (p < 0.05). HE4 showed a significantly higher AUC than CA125 (p < 0.05). For postmenopausal women, CA125 performed equivalently to ROMA (p = 0.73) and CPH-I (p = 0.91). CONCLUSIONS: In identifying patients with OC, ROMA and CPH-I outperformed single tumor marker. The diagnostic performance of HE4 was significantly higher than that of CA125. CA125 was more suitable for postmenopausal women.

Comparison of the risk of ovarian malignancy algorithm and Copenhagen Index for the preoperative assessment of Japanese women with ovarian tumors.

OBJECTIVE: To compare the risk of ovarian malignancy algorithm (ROMA) and Copenhagen Index (CPH-I) in their ability to distinguish epithelial ovarian cancer (EOC) and malignant ovarian tumors (MLOT) from benign ovarian tumors (BeOT) in Japanese women. METHODS: Patients with pathologically diagnosed ovarian tumors were included in this study. The study validated the diagnostic performance of ROMA and CPH-I. RESULTS: Among the 463 Japanese women included in this study, 312 had BeOT, 99 had EOC, and 52 had other MLOT. The receiver-operator characteristic (ROC) area under the curve (AUCs) of ROMA (0.89) and CPH-I (0.89) for distinguishing EOC from BeOT were significantly higher than that of CA125 (0.82) (CA 125 vs. ROMA; p = 0.002, vs. CPH-I; p < 0.001). The ROC-AUCs of ROMA (0.82) and CPH-I (0.81) for distinguishing MLOT from BeOT were significantly higher than that of CA125 (0.75) (CA 125 vs. ROMA: p = 0.003, vs. CPH-I: p < 0.001). The sensitivity (SN)/specificity (SP) of ROMA and CPH-I for distinguishing EOC from BeOT at standard cut-off points were 69%/90%, and 69%/90%, respectively, those for distinguishing MLOT from BeOT were 54%/90%, and 55%/90%, respectively. CONCLUSION: ROMA and CPH-I performed comparably well and better than CA125 in distinguishing EOC from BeOT in Japanese women. ROMA and CHP-I should be used with caution in practical situations, where all histological possibilities for must be considered, because the SNs of ROMA and CPH-I were only 54% and 55%.

The role of diffusion-weighted imaging in the evaluation of adnexal lesions.

Purpose: Magnetic resonance imaging (MRI) has been used as a problem-solving tool in the diagnosis of adnexal lesions. Both benign and malignant ovarian masses can present as complex adnexal lesions. Preoperative diagnosis of malignancy is essential for planning the surgical approach and appropriate treatment regimen. The aim of our study was to determine the role of diffusion-weighted MRI (DWI) in differentiating benign from malignant adnexal lesions. Material and methods: Fifty-five patients (constituting 67 lesions) referred to MRI for evaluation of adnexal lesions were studied using 1.5 T MRI. The signal on DWI (qualitative) and ADC values (quantitative DWI) of the solid and cystic components of the lesions were analysed separately. Chi-square test, cross tabulation, and ROC curves were used to determine features on DWI that could distinguish benign from malignant lesions. Results: Of the 67 lesions, 50 were benign and 17 were malignant. There was a significant association of hyperintense signal of solid components on T2W and DWI with malignancy, with a p-value of 0.003 and 0.001, respectively. Benign lesions showed hypointense signal on T2W and DWI. ADC values of the solid components could not distinguish benign from malignant lesions; p = 0.290. The signal intensity and ADC values of the cystic fluid in benign and malignant lesions showed a significant overlap. Conclusions: Qualitative DWI acts as an adjunct to conventional MRI in differentiating benign from malignant adnexal lesions showing solid/mixed morphology. It plays no role in distinguishing lesions based on their cystic components. ADC values play no role in differentiating benign from malignant adnexal lesions irrespective of lesion morphology.

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

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 diagnosed by gynecologic examination / ultrasound who were hospitalized at the Departments of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy Hospital and Hue Central Hospital, Vietnam, between January 2018 and June 2020. ROMA and CPH-I were calculated based on measurements of serum carbohydrate antigen (CA-125) and human epididymis protein (HE4). The final diagnosis was based on clinical features, radiologic and histologic findings, and the International Federation of Gynecology and Obstetrics (FIGO) 2014 stages of ovarian cancer were recorded. Matching the values of ROMA and CPH-I to postoperative histopathology reports resulted in the preoperative prediction values. 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 74.2% and 91.8%, 87.1% and 78.5%, respectively. The optimal cut-off for CPH-I was 1.89%. The areas under the ROC curves (AUCs) of ROMA and CPH-I were 0.882 (95% CI: 0.849-0.909) and 0.898 (95% CI: 0.867-0.924), respectively. CONCLUSIONS: The introduction of the Copenhagen Index to help stratify the malignancy risk of ovarian tumors, irrespective of menopausal status, might be applied as a simple alternative with a similar efficacy to ROMA in clinical practice.

Prevalence of human papillomavirus detection in ovarian cancer: a meta-analysis.

We conducted a meta-analysis of published data to update and estimate the prevalence of HPV in ovarian cancer. A comprehensive literature search was performed according to the PRISMA guidelines. Eligible articles published from 1989 until 2020 by searching Web of Sciences, Pubmed, Embase, and the Cochrane Library Central databases were gathered. A pooled estimation of HPV prevalence with a 95% confidence interval (CI) was calculated based on a random effect model. Quantitative assessment of heterogeneity was explored using Cochrane test and I2. Additionally, publication bias, sensitivity, meta-regression, and subgroup analyses were also performed. Twenty-nine studies involving 2280 patients with ovarian cancer were included. The statistical heterogeneity was high (I2 = 88%, P<0.0001). The pooled prevalence of HPV in ovarian cancer cases was 15.9% (95% CI, 11-22). In subgroup analyses, the highest prevalence of HPV was reported by studies from Asia (30.9%; 95% CI, 20-44) and Eastern Europe (29.3%; 95% CI, 4.4-78). Furthermore, the most frequently detected HPV genotype was HPV16 (54%; 95% CI, 27.9-55), followed by HPV18 (23.2%; 95% CI, 18.8-28.2). Our meta-analysis suggests a great difference in the prevalence of HPV detected in ovarian cancer by different studies, which is not seen in strongly HPV-associated cancers such as cervical cancer. However, the prevalence varied markedly by geographic region. Considering the substantial heterogeneity found, more studies with control groups and precise assays measuring HPV mRNA expression are needed to further evaluate the link and causative aetiology between HPV and ovarian cancer.

The Endometrioma Treatment Paradigm when Fertility Is Desired: A Systematic Review.

OBJECTIVE: To establish an endometrioma treatment paradigm (decision tree) in the treatment of an ovarian endometrioma through the review of current literature. DATA SOURCES: A thorough literature search, including PubMed, Google Scholar, and the Cochrane Library, was performed from April 2020 to July 2020. The review was completed by using the following keywords: METHODS OF STUDY SELECTION: Articles published in English that addressed the endometrioma in regard to the following were included: (1) diagnosis, (2) treatment of pain on the basis of size and/or surgical intervention, (3) treatment of fertility on the basis of size and/or surgical intervention, (4) surgical technique, (5) in vitro fertilization success on the basis of size and/or surgical intervention, (6) risk of rupture at the time of egg retrieval, (7) impact on the antimüllerian hormone and antral follicle count postsurgery, and (8) impact on implantation. TABULATION, INTEGRATION, AND RESULTS: Fifty-six articles were included in this systematic review. While conducting this literature review, several themes were noted. In general, the literature on the ovarian endometrioma seems to be homogeneous in regard to imaging the endometrioma, excision rather than desiccation for an endometrioma ≥3-cm causing pain and/or infertility, minimal use of bipolar energy at the time of ovarian surgery, and risk of severe infection secondary to inadvertent rupture of cysts during egg retrieval. Conversely, studies on the ovarian endometrioma are much more heterogeneous in terms of surgery and assisted reproductive technology, that is, whether surgery should be performed. Certainly, an endometrioma ≥5-cm should be excised before assisted reproductive technology. Moreover, it seems that the antral follicle count and implantation may be enhanced with surgery. CONCLUSION: By completing an extensive literature review, an easy-to-use algorithm for the diagnosis, evaluation, and treatment of endometriomas was developed to help clinicians in their treatment of patients with endometriosis in the short and long terms.

Retrospective study of ovarian malignancy managed in surgical unit at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore.

OBJECTIVE: To determine the oncological outcome and pattern of ovarian tumours in patients who underwent surgical management. METHODS: The retrospective, descriptive hospital-based study was conducted at Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan, and comprised data of all patients who underwent surgical intervention for ovarian cancer between January 2010 and December 2015. Data was retrieved from the hospital database and analysed using SPSS 20. RESULTS: Of the 236 patients, 203(86%) had undergone open surgery, while 33(14%) had had laparoscopic surgery. Neo-adjuvant chemotherapy was given in 60(25.42%) cases and adjuvant chemotherapy in 102(43.22%). Epithelial ovarian cancer in 201(85.16%) cases was the most common tumour type. Mortality was recorded in 36(15.5%) cases, while 41(19.9%) were lost to follow-up. CONCLUSIONS: Ovarian tumours were found to be difficult to treat and were associated with frequent recurrence.

The role of "penumbra sign" and diffusion-weighted imaging in adnexal masses: do they provide a clue in differentiating tubo-ovarian abscess from ovarian malignancy?

PURPOSE: To evaluate the role of "penumbra sign", diffusion-weighted imaging (DWI), and the apparent diffusion coefficient (ADC) value in differentiating tubo-ovarian abscess (TOA) from ovarian malignancy. MATERIAL AND METHODS: Thirty-six patients with 50 adnexal masses (tubo-ovarian abscess, n = 24; ovarian malignancy, n = 26), who underwent magnetic resonance imaging (MRI) with DWI, were retrospectively evaluated. "Penumbra sign" (hyperintense rim on T1W images), diffusion restriction, and mean apparent diffusion coefficient (ADC) values from cystic (c-ADC) and solid (s-ADC) components were evaluated for all the masses. RESULTS: "Penumbra sign" on T1W images was significantly more common in the TOA group (n = 21, 87.5%) than in the ovarian malignancy group (n = 2, 7.7%) (p < 0.001). Similarly, diffusion restriction in the cystic component was more frequent in the TOA group (n = 24, 100% vs. n = 2, 10.5%; p < 0.001). In contrast, diffusion restriction in the solid component was more common in the ovarian malignancy group (n = 5, 20.8% vs. n = 26, 100%; p < 0.001). The mean c-ADC value was significantly lower in TOAs (p < 0.001). A c-ADC value of 1.31 × 10-3 mm2/s may be an optimal cut-off in distinguishing TOAs from ovarian malignancies. Conversely, the mean s-ADC value was significantly lower in the ovarian malignancy group (p < 0.001). An s-ADC value of 0.869 × 10-3 mm2/s may be an optimal cut-off in differentiating ovarian malignancies from TOAs (p < 0.001). ROC curve analysis showed that c-ADC values had a higher diagnostic accuracy than s-ADC values. CONCLUSIONS: "Penumbra sign" on T1W images, diffusion characteristics, and ADC values provide important clues in addition to conventional MR imaging features in differentiating TOA from ovarian malignancy.

Endometriomas with low-risk malignancy potential in ultrasonography with high human epididymis protein 4 and risk of ovarian malignancy algorithm: a cases series.

Endometriosis is an estrogen-dependent disease that affects 5 to 15% of women of reproductive age. Data from large-cohort and case-control studies indicate an increased risk for ovarian cancers in women with endometrioma. Recently, as an ovarian cancer biomarker, human epididymal secretory protein E4 (HE4) has been increasingly investigated in the differentiating of endometrioma from ovary malignancy and in confirming the benign structure of the endometrioma. This case series study describes women who underwent surgery due to increased serum HE4 levels and higher Risk of Ovarian Malignancy Algorithm (ROMA) index, in whom the final pathology was reported as benign, although, ultrasonography and magnetic resonance imaging (MRI) findings showed features of "typical" endometrioma.

The role of preoperative imaging and tumor markers in predicting malignant ovarian masses in children.

PURPOSE: To investigate the clinicopathololgic characteristics and the predicting value of preoperative imaging and tumor markers in children with ovarian masses. METHODS: Patients admitted in Shanghai children's hospital with ovary neoplasms between 2010.01 and 2015.12 were retrospectively analyzed. The medical records including age at operation, presentation of symptoms and signs, tumor marker, imaging, pathology, tumor diameter and surgical choice were reviewed. All data were analyzed using SPSS 17.0 RESULTS: A total of 139 patients were included, among which 116 were benign neoplasms and 23 malignant tumors. There was significance difference relation with the tumor diameter, character, torsion and tumor markers, but not the age, position, calculi, and symptoms. The risk factors include tumor diameters ≥ 10 cm, the odds ratio (OR) was 11, 95% confidence interval (CI) was 3-36, solid/complex tumor (OR 6, 95% CI 2, 14) and positive in tumor markers (OR 84, 95% CI 20, 345). Among the patients with benign neoplasms, 77 of them had laparoscopic ovarian cystectomy while 23 patients with malignant tumors had salpingo-oophorectomy and omentum resection. CONCLUSION: Preoperative imaging and tumor markers could help identifying the malignant ovarian masses in children. If tumor diameter ≥ 10 cm, solid/complex in imaging and tumor markers abnormal, a radical resection is mandatory; otherwise, an ovarian-sparing surgery is recommended.

Ethnic disparity in clinical performance between multivariate index assay and CA125 in detection of ovarian malignancy.

Aim: Based on evidence that African-American (AA) women have lower CA125 values than Caucasian (C) women, we investigated this to see if this disparity would have an impact on ovarian cancer detection using CA125 and multivariate index assay (MIA). Materials & methods: Serum from two prospective trials of 1029 (274 malignancies [250 C/24AA]) were analyzed for CA125 and MIA results. Clinical performance was calculated. Results: Sensitivity of MIA in Caucasian women was 93.2%, 74.4% for CA125 at the ACOG approved cut-off level of 200 U/ml cutoff, and 80.4% using the 2007, Dearking 67 U/ml cutoff. In AA American women, MIA sensitivity was 79.2%, 33.3% for CA125 at the ACOG approved cut-off levels and 62.5% at the 2007, Dearking 67 U/ml cutoff. Conclusion: Our results support that CA125 in AA women with adnexal masses has lower sensitivity than MIA no matter what the cutoff value is. Implementation of MIA in evaluation of adnexal masses should increase sensitivity of detection of malignancy compared with CA125, particularly in AA women.

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.

Falsely elevated human epididymis protein 4 results and Risk of Ovarian Malignancy Algorithm in polymorbid women after solid organ transplantation: A pilot and case-control study.

BACKGROUND: Cancer prevention is essential after transplantation (Tx). The use of HE4 and Risk of Ovarian Malignancy Algorithm (ROMA) is recommended as a tool for selective ovarian cancer screening; however, creatinine is a known confounder. This study assessed the reliability of HE4, CA125, and ROMA after Tx. METHODS: We matched a total of 202 women without gynecological malignancies and 236 men by age and serum creatinine. Each pair consisted of a patient after Tx (kidney, liver, heart, and pancreas) and a diseased but non-Tx consecutive patient. Serum HE4, CA125 (Roche Cobas 6000), and creatinine (enzymatic, Abbott Architect) were measured in all patients. RESULTS: Creatinine correlated with HE4 (women: r = .864, P < .0001; men: r = .848, P < .0001). Age correlated slightly with HE4 in women (r = .250, P < .005) and men (r = .240, P < .0005). HE4 in women after Tx (median of 84.8 pmol/L) was significantly higher than non-Tx women (53.7 pmol/L, P < .0001) in the reference range of serum creatinine. Neither HE4 nor CA125 correlated with tacrolimus concentration, but anemia, hyperparathyroidism, kidney, liver, and lung diseases were possible confounders for HE4 after transplantation (P < .05). CONCLUSION: Human epididymis protein 4 (HE4) was significantly increased in women after solid organ transplantation compared to levels without transplants matched by age and serum creatinine. HE4 results may be misleading in these patients.

[Diagnosis and management in pediatric patients with ovarian masses]. / Diagnóstico y manejo de masas ováricas en pacientes pediátricas.

OBJECTIVE: Review of the diagnosis and management of ovarian masses in children, through the identification of preoperative risk factors of malignancy, the evaluation of surgical management and its results. METHODS: Retrospective study in pediatric patients under 18 years old, managed surgically by ovarian masses. Analyzed data were symptoms, imagining, tumor markers, treatment, outcomes and pathology. The primary endpoint was ovarian malignancy. RESULTS: We identified 54 patients with ovarian masses between 2014 and 2017, of which 49 were benign and 5 malignant; The malignant ovarian masses were significantly larger than the benign, with an average of 19.4 cm vs 6.49 cm (p = 0.0001); had greater solid component in the imaging and positive tumor markers (p = 0.001) and were treated with oophorectomy plus tumor staging surgery. Forty-three patients with benign tumors underwent ovarian preservation surgery. The postoperative follow-up of all the patients was on average 3.4 months (1-25 months) and 20.3% presented pelvic pain associated with alterations of the menstrual cycle in their postoperative control. There are no reports of recurrence or contralateral ovarian tumor. CONCLUSIONS: Large masses with solid components and positive tumor markers were significant predictors of malignancy. Minimally invasive ovarian preserving surgery should be considered as the first treatment option in masses with low risk of malignancy. On the other hand, oophorectomy plus tumor staging surgery should be considered for ovarian tumors with a high risk of malignancy.

OBJETIVO: Revisión del diagnóstico y manejo de las masas ováricas en población infantil, mediante la identificación de factores de riesgo preoperatorios de malignidad, la evaluación del manejo quirúrgico y sus resultados. METODOS: Estudio retrospectivo en pacientes pediátricas menores de 18 años, intervenidas quirúrgicamente por masas ováricas. Se analizaron datos como síntomas, imágenes diagnósticas, marcadores tumorales, tratamiento, resultados y patología. La variable principal fue malignidad ovárica. RESULTADOS: Se identificaron 54 pacientes con masas ováricas entre el año 2014 a 2017, de las cuales 49 fueron benignas y 5 malignas. Las masas ováricas malignas fueron significativamente más grandes que las benignas, con media de 19,4 cm vs 6,49 cm (p = 0,0001); tuvieron mayor componente sólido en los hallazgos imagenológicos y marcadores tumorales positivos (p = 0,001) y fueron tratadas con ooforectomía más cirugía de estadificación tumoral. A 43 pacientes con tumores benignos se les realizó cirugía preservadora de ovario. El seguimiento postoperatorio de todas las pacientes fue en promedio de 3,4 meses (1-25 meses) y el 20,3% presentaron dolor pélvico asociado a alteraciones del ciclo menstrual en su control postoperatorio. No hay reportes de recidiva ni tumor de ovario contralateral. CONCLUSIONES: Masas grandes, con componentes sólidos y marcadores tumorales positivos fueron predictores significativos de malignidad. La cirugía preservadora de ovario por vía mínimamente invasiva debe ser considerada como primera opción de tratamiento en masas con bajo riesgo de malignidad; Por otra parte, la ooforectomía más cirugía de estadificación tumoral, debe ser considerada para los tumores ováricos con alto riesgo de malignidad.

A new strategy for calculating the risk of ovarian malignancy algorithm (ROMA).

BACKGROUND: Reliable quantitative measurements of HE4 and CA125 levels are required to calculate the risk of ovarian malignancy algorithm (ROMA) value. We suggest a new reporting strategy for interpreting ROMA values based on analytical measurement range (AMR) and qualified-intervals of the HE4 and CA125 results. METHODS: HE4 and CA125 assays from Abbott and Roche were used. The AMRs and the qualified-intervals were as follows: Architect HE4 assay, 20-1500 and 17.2-2637.8 pmol/L; Architect CA125 II assay, 1-1000 and 3.9-14,163.0 U/mL; Elecsys HE4 assay, 15-1500 and 28.8-3847 pmol/L; Elecsys CA125 II assay, 0.6-5000 and 6.5-5000 U/mL. These values were used to simulate the ROMA values. RESULTS: Reporting algorithm for the ROMA value could be classified into three categories. (1) If quantitative HE4 and CA125 levels are reliable, the numerical ROMA value can be reported. (2) If HE4 value is <20 and <28.8 for Abbott and Roche in premenopausal woman, the ROMA value should be reported as "low risk" regardless of the CA125 result. In postmenopausal woman, however, it should be reported as "low risk" (CA125<203.0 and <165.8 for Abbott and Roche) or "undetermined" (vice-versa value). (3) If CA125 value is <3.9 and <6.5 for Abbott and Roche, it should be reported as "low risk" (premenopausal HE4<51.5 and <62.2, postmenopausal HE4<323.0 and <281.5 for Abbott and Roche) or "undetermined" (vice-versa value). CONCLUSIONS: New reporting strategy will provide more informative reporting of ROMA values in clinical practice.

Diagnostic performance and establishment of reference limits of HE4 in Korean healthy women.

OBJECTIVE: We aimed to establish distribution and reference limits of HE4 and risk of ovarian malignancy algorithm (ROMA) in healthy Korean women and investigated the factors influencing HE4 levels. We also investigated the diagnostic performances of HE4 and ROMA score, compared with CA125. METHODS: We collected specimens from 1809 healthy Korean women, 140 specimens from patients with ovarian cancers (OCs) and 123 specimens from patients with benign ovarian tumor. Serum HE4 and CA125 concentrations were measured using an electrochemiluminescence immunoassay. The receiver operator characteristic (ROC) curve analysis was done for ROMA, HE4, CA125 and combining of HE4 and CA125. RESULTS: HE4 level was influenced by age, not by menopausal status. The 97.5th percentile upper reference limit of HE4 of subjects <50years and ≥50year-old was 63.87pmol/L and 88.28pmol/L, respectively. The 97.5th percentile upper reference limits of ROMA score were 13.66 in premenopausal and 19.30 in postmenopausal women. The serum HE4 level was even lower in the patients with benign tumor compared to those in healthy controls. HE4 had significantly higher concentrations in OCs than benign ovarian tumor (P<0.001). ROMA and HE4 combined with CA125 or not performed better diagnostically than CA125 alone for distinguishing OCs, with AUCs of 0.844 for ROMA, 0.827 for combining of HE4 and CA125, 0.825 for HE4, and 0.795 for CA125. CONCLUSIONS: The reference limit of HE4 was different from those reported by other studies, suggesting racial or regional difference. HE4 and ROMA were better than CA125 for differentiation normal and benign ovarian tumor from OCs. (Word count: 253).

Adolescent ovarian masses: A retrospective analysis.

A retrospective study was conducted to review incidence, clinical practice, surgical management and histology of adolescent ovarian masses in order to audit and improve future practices. Complete hospital records of all adolescents between 10 and 20 years who had undergone surgery for ovarian masses were analysed between November 2006 to 2014. Parameters analysed were age, clinical features, diagnosis, operative procedure and histopathology. Ninety-four patients were included in the study and among them, 37 had non-neoplastic masses, 30 had benign neoplasms while 27 had malignant tumors. The main clinical presentations were abdominal pain (54%) and abdominal mass (41%). Dermoid was the most common benign neoplasm while germ cell tumor was the most common malignant mass; dysgerminoma being the commonest (68%). Malignancy was more common in early adolescence (12 ± 4.8 years) while non-neoplastic masses were seen more frequently in late adolescence (17.7 ± 2.2 years). There was a fair correlation between ultrasound and histopathological diagnosis.

HE4, CA125, the Risk of Malignancy Algorithm and the Risk of Malignancy Index and complex pelvic masses - a prospective comparison in the pre-operative evaluation of pelvic masses in an Australian population.

BACKGROUND: Human epididymis protein 4 (HE4) has been proposed as a novel biomarker for the diagnosis of epithelial ovarian cancer. Using HE4 and CA125, the risk of malignancy algorithm (ROMA) has been shown to be effective in the stratification of epithelial ovarian cancer risk. AIMS: To determine the effectiveness of HE4 and ROMA in the diagnosis of malignancy of women presenting with a complex pelvic mass in an Australian population and to compare it with CA125 and the risk of malignancy index (RMI). MATERIALS AND METHODS: Prospective recruitment of women was conducted between October 2012 and March 2014 (n = 50). CA125 and HE4 serum concentrations were collected and stored for subsequent analysis. Sensitivities, specificities, positive predictive values (PPV) and negative predictive values (NPV) were calculated for HE4, CA125, ROMA and the RMI. Receiver operating characteristic (ROC) area under the curves (AUC) were also calculated for comparison. RESULTS: There was a higher HE4 level in women with ovarian cancer compared with women with benign pathology (P = 0.008), and this observation was seen in benign versus stage 1 ovarian cancer women (P = 0.025). HE4 had a better specificity than CA125 for the diagnosis of ovarian cancer in all women (P = 0.022), and this effect was also observed in premenopausal women (P = 0.012). Furthermore, the ROC-AUC for HE4 was superior than CA125 in all women (P = 0.0451). The ROMA algorithm was not inferior to the RMI calculation in this population. CONCLUSIONS: In an Australian population, HE4 and ROMA are useful in the diagnosis of epithelial ovarian cancer.