title: Symptoms, CA125 and HE4 for the preoperative prediction of ovarian malignancy in Brazilian women with ovarian masses.
abstract: BACKGROUND
  This manuscript evaluates whether specific symptoms, a symptom index (SI), CA125 and HE4 can help identify women with malignant tumors in the group of women with adnexal masses previously diagnosed with ultrasound.
  
  
  METHODS
  This was a cross-sectional study with data collection between January 2010 and January 2012. We invited 176 women with adnexal masses of suspected ovarian origin, attending the hospital of the Department of Obstetrics and Gynecology of the Unicamp School of Medicine. A control group of 150 healthy women was also enrolled. Symptoms were assessed with a questionnaire tested previously. Women with adnexal masses were interviewed before surgery to avoid recall bias. The Ward Agglomerative Method was used to define symptom clusters. Serum measurements of CA125 and HE4 were made. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using standard formulae.
  
  
  RESULTS
  Sixty women had ovarian cancer and 116 benign ovarian tumors. Six symptom clusters were formed and three specific symptoms (back pain, leg swelling and able to feel abdominal mass) did not agglomerate. A symptom index (SI) using clusters abdomen, pain and eating was formed. The sensitivity of the SI in discriminating women with malignant from those with benign ovarian tumors was 78.3%, with a specificity of 60.3%. Positive SI was more frequent in women with malignant than in women with benign tumors (OR 5.5; 95% CI 2.7 to 11.3). Elevated CA125 (OR 11.8; 95% CI 5.6 to 24.6) or HE4 (OR 7.6; 95% CI 3.7 to 15.6) or positive ROMA (OR 9.5; 95% CI 4.4 to 20.3) were found in women with malignant tumors compared with women with benign tumors. The AUC-ROC for CA125 was not different from that for HE4 or ROMA. The best specificity and negative predictive values were obtained using CA125 in women with negative SI.
  
  
  CONCLUSIONS
  Women diagnosed with an adnexal mass could benefit from a short enquiry about presence, frequency and onset of six symptoms, and CA125 measurements. Primary care physicians can be thereby assisted in deciding as to whether or not reference the woman to often busy, congested specialized oncology centers.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medical Sciences, State University of Campinas - Unicamp, Campinas, SP 13083-970, Brazil. derchain@fcm.unicamp.br.
authors.forename: Denise da Rocha
authors.initials: Dda R
authors.lastname: Pitta
authors.forename: Luis Otávio
authors.initials: LO
authors.lastname: Sarian
authors.forename: Amilcar
authors.initials: A
authors.lastname: Barreta
authors.forename: Elisabete Aparecida
authors.initials: EA
authors.lastname: Campos
authors.forename: Liliana Lucci de Angelo
authors.initials: LL
authors.lastname: Andrade
authors.forename: Ana Maria Dias
authors.initials: AM
authors.lastname: Fachini
authors.forename: Leonardo Martins
authors.initials: LM
authors.lastname: Campbell
authors.forename: Sophie
authors.initials: S
authors.lastname: Derchain
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000097:blood; D001938:Brazil; D018394:CA-125 Antigen / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D010053:Ovary / Q000473:pathology*; D057234:Preoperative Period; D011379:Prognosis; D011506:Proteins / Q000378:metabolism*; D012680:Sensitivity and Specificity; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human
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