Symptoms, CA125 and HE4 for the preoperative prediction of ovarian malignancy in Brazilian women with ovarian masses.

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. CONCLUSION: 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.

HE4 can help discriminate women with malignant ovarian tumors only if CA125 levels are elevated.

Objective: To evaluate the performance of mesothelin, CA125, HE4 and ROMA index in the detection of malignant ovarian tumors. 
Study Design: This is a cross-sectional study including 199 women with adnexal masses (67 with malignant tumors and 132 with benign tumors) and 150 healthy women (controls). We used a recursive multivariate partitioning algorithm to assess the contribution of each of the serum markers and the ROMA index to the discrimination of women with malignant tumors. Also, the areas under the ROC curves (AUC) for each of the serum markers and for the ROMA index were compared using the Venkatraman's projection-permutation test. 
Results: In the recursive model, CA125 had the best performance in discriminating women with malignant tumors. In women with normal-range CA125 levels, none of the other markers contributed to the discrimination of women with malignant tumors. In women with elevated CA125 levels, elevated HE4 levels were associated with an increased risk of harboring a malignant tumor. The AUC for mesothelin was smaller than that for all the other curves, and both the ROMA index and CA125 had better AUC than HE4. 
 Conclusion: In women with normal CA125 levels, neither mesothelin nor HE4 contributed to discriminate women with malignant ovarian tumors; however, for women with elevated CA125 levels HE4 may help discriminating those who have a malignant ovarian tumor.

[Prevalence of Chlamydia trachomatis infection among women candidates for in vitro fertilization at a public institution of the State of São Paulo, Brazil]. / Prevalência de infecção por Chlamydia trachomatis em mulheres candidatas à fertilização in vitro em serviço público de referência do Estado de São Paulo.

PURPOSE: To evaluate the prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) among women candidates to in vitro fertilization (IVF) in a reference public service in southeastern Brazil. METHODS: Women who were referred for IVF from April 1st, 2008 to December 31st, 2009 were enrolled sequentially in the study. A gynecological-obstetrical background questionnaire was applied and endocervical swab samples were obtained to search for CT and NG using hybrid capture and PCR. The variables studied were: age, color, education, duration of infertility, number of pregnancies and living children, history of miscarriage, ectopic pregnancy, number of sex partners, pelvic inflammatory disease (PID), pelvic surgery, manipulation of the uterine cavity, smoking, and illicit drug use. The women were distributed according to the presence/absence of confirmed chlamydia infection and descriptive analysis was employed. RESULTS: Among 176 women tested the prevalence of CT infection was 1.1% and there was no NG infection. Two thirds of the women were ≥30 years old, with schooling ≥8 years and ≤5 years of infertility, and 56.2% had no children. The main background data were pelvic surgery (77.8%), manipulation of the uterine cavity (62.5%) and PID (27.8%). The tubal factor was the most prevalent, 73.3% of women (from 129), 37.5% had been sterilized, 35.8% had not been sterilized, and other factors had a prevalence <30%. CONCLUSIONS: CT and NG infections had a low prevalence in this sample. Studies at other centers in the country are needed to confirm the prevalence of infection in this particular group of infertile women.

Inclusão dos sintomas na discriminação entre tumores anexiais benignos e malignos / Inclusion of symptoms in the discrimination between benign and malignant adnexal masses

OBJETIVO: Avaliar a associação entre sintomas clínicos e malignidade em mulheres com tumores anexiais, submetidas à cirurgia. MÉTODOS: Estudo de corte transversal com coleta prospectiva, no qual foram incluídas 105 mulheres, atendidas em um hospital de ensino do Estado de São Paulo de novembro de 2009 a março de 2011, devido ao tumor anexial e à indicação de laparotomia/laparoscopia. Todas foram submetidas a uma entrevista estruturada sobre a ocorrência de 18 sintomas associados ao câncer de ovário. A entrevista incluiu gravidade, frequência e duração dos sintomas nos 12 meses prévios à primeira consulta. Também foram avaliados os níveis de CA125 e a classificação ultrassonográfica. Foi calculada para cada sintoma a razão de prevalência com intervalo de confiança de 95%. O padrão-ouro foi o resultado do exame anatomopatológico das peças cirúrgicas. RESULTADOS: Das 105 mulheres incluídas, 75 (71,4%) apresentaram tumores benignos e 30 (28,6%), malignos. Em mulheres com tumores malignos, os sintomas foram mais frequentes, dentre eles: inchaço abdominal (70%), aumento do volume abdominal (67%), dor pélvica (60%), irregularidade menstrual (60%), empachamento (53%), dor abdominal (50%), dor nas costas (50%) e saciedade precoce (50%). As mulheres com tumores benignos apresentaram essencialmente dor pélvica (61%), irregularidade menstrual (61%) e inchaço abdominal (47%). Os sintomas significativamente associados com malignidade foram: sensação de inchaço abdominal (RP=2,0; IC95% 1,01 - 3,94), aumento objetivo do volume abdominal (RP=2,16; IC95% 1,12 - 4,16), dor nas costas (RP=1,97; IC95% 1,09 - 3,55), empachamento (RP=2,25; IC95% 1,25 - 4,07), saciedade precoce (RP=2,06; IC95% 1,14 - 3,70), massa abdominal (RP=1,83; IC95% 1,01 - 3,30), dificuldade para deglutir (RP=1,98; IC95% 1,10 - 3,56) e sangramento pós-menopausa (RP=2,91; IC95% 1,55 - 5,44). A presença de dor pélvica, constipação, dispareunia, fadiga, dor abdominal, náusea e/ou vômito, irregularidade menstrual, perda de peso, diarreia e sinusorragia foram semelhantes nos dois grupos. CONCLUSÕES: Em mulheres com tumores anexiais com indicação cirúrgica, a avaliação pré-operatória dos sintomas pode auxiliar na predição da malignidade.

PURPOSE: To assess the association between clinical symptoms and the diagnosis of malignancy in women with adnexal tumors who underwent surgery. METHODS: Cross-sectional study, in which 105 women with adnexal tumors and indication for laparotomy/laparoscopy were included. All women were treated at a teaching hospital in the state of São Paulo between November 2009 and March 2011. All patients underwent a structured interview about the occurrence of 18 symptoms associated with ovarian cancer. The interview included the severity, frequency, and duration of these symptoms in the 12 months prior to the first medical consultation. The CA125 levels and the ultrasound classification of the tumors were also evaluated. We calculated for each symptom the prevalence ratio with 95% confidence intervals. The golden-standard was the result of the pathological examination of the surgical specimens. RESULTS: Of the 105 women included, 75 (71.4%) had benign tumors and 30 (28.6%) had malignant ones. In women with malignant tumors, the most frequent symptoms were: abdominal bloating (70%), increased abdominal size (67%), pelvic pain (60%), menstrual irregularity (60%), swelling (53%), abdominal pain (50%), backache (50%), and early repletion (50%). Women with benign tumors showed essentially pelvic pain (61%), menstrual irregularities (61%), and abdominal swelling (47%). Symptoms significantly associated with malignancy were: bloating (PR=2.0; 95%CI 1.01 - 3.94), increased abdominal size (PR=2.16; 95%CI 1.12 - 4.16), backache (RP=1.97; 95%CI 1.09 - 3.55), swelling (PR=2.25; 95%CI 1.25 - 4.07), early repletion (RP=2.06; 95%CI 1.14 - 3.70), abdominal mass (PR=1.83; 95%CI 1.01 - 3.30), eating difficulties (PR=1.98; 95%CI 1.10 - 3.56), and postmenopausal bleeding (PR=2.91; 95%CI 1.55 - 5.44). The presence of pelvic pain, constipation, dyspareunia, fatigue, abdominal pain, nausea or vomiting, menstrual irregularity, weight loss, diarrhea, and bleeding after intercourse was similar in both groups. CONCLUSIONS: In women with adnexal tumors including indication of surgical treatment, the preoperative evaluation of symptoms may help predicting malignancy.

Prevalência de infecção por Chlamydia trachomatis em mulheres candidatas à fertilização in vitro em serviço público de referência do Estado de São Paulo / Prevalence of Chlamydia trachomatis infection among women candidates for in vitro fertilization at a public institution of the State of São Paulo, Brazil

OBJETIVO: Avaliar a prevalência de infecção por Chlamydia trachomatis (CT) e Neisseria gonorrhoeae (NG) em mulheres candidatas ao tratamento tópico e de fertilização in vitro (FIV) em serviço público de referência da Região Sudeste do Brasil. MÉTODOS: Mulheres que tiveram indicação de FIV, no período de 1º de abril de 2008 a 31 de outubro de 2009, foram admitidas sequencialmente no estudo. Foi aplicado um questionário sobre antecedentes ginecológicos e obstétricos e coletada amostra de swab endocervical para pesquisa de CT e NG através de captura híbrida e PCR. As variáveis estudadas foram: faixa etária, cor, escolaridade, tempo de infertilidade, número de gestações e filhos vivos, antecedentes de aborto, gestação ectópica, número de parceiros, Doença Inflamatória Pélvica (DIP), cirurgia pélvica, manipulação de cavidade uterina, tabagismo e uso de drogas ilícitas. As mulheres foram distribuídas segundo presença ou não de infecção por clamídia e a análise foi descritiva. RESULTADOS: Entre as 176 mulheres estudadas a prevalência de infecção por CT foi de 1,1%, não houve infecção por NG. Dois terços das mulheres tinham idade >30 anos, escolaridade >8 anos, <5 anos de infertilidade e 56,2% não tinham filhos. Os principais antecedentes foram cirurgia pélvica (77,8%), manipulação de cavidade uterina (62,5%) e DIP (27,8%). O fator tubário foi o mais prevalente, em 129 mulheres (73,3%), 37,5% com e 35,8% sem laqueadura, os demais fatores tiveram prevalência <30%. CONCLUSÕES: As infecções por CT e NG tiveram baixa prevalência na amostra estudada e são necessários estudos em outros centros do país para confirmar a prevalência de infecções nesse grupo particular de mulheres inférteis.

PURPOSE: To evaluate the prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) among women candidates to in vitro fertilization (IVF) in a reference public service in southeastern Brazil. METHODS: Women who were referred for IVF from April 1st, 2008 to December 31st, 2009 were enrolled sequentially in the study. A ginecological-obstetrical background questionnaire was applied and endocervical swab samples were obtained to search for CT and NG using hybrid capture and PCR. The variables studied were: age, color, education, duration of infertility, number of pregnancies and living children, history of miscarriage, ectopic pregnancy, number of sex partners, pelvic inflammatory disease (PID), pelvic surgery, manipulation of the uterine cavity, smoking, and illicit drug use. The women were distributed according to the presence/absence of confirmed chlamydia infection and descriptive analysis was employed. RESULTS: Among 176 women tested the prevalence of CT infection was 1.1% and there was no NG infection. Two thirds of the women were >30 years old, with schooling >8 years and <5 years of infertility, and 56.2% had no children. The main background data were pelvic surgery (77.8%), manipulation of the uterine cavity (62.5%) and PID (27.8%). The tubal factor was the most prevalent, 73.3% of women (from 129), 37.5% had been sterilized, 35.8% had not been sterilized, and other factors had a prevalence <30%. CONCLUSIONS: CT and NG infections had a low prevalence in this sample. Studies at other centers in the country are needed to confirm the prevalence of infection in this particular group of infertile women.

[Inclusion of symptoms in the discrimination between benign and malignant adnexal masses]. / Inclusão dos sintomas na discriminação entre tumores anexiais benignos e malignos.

PURPOSE: To assess the association between clinical symptoms and the diagnosis of malignancy in women with adnexal tumors who underwent surgery. METHODS: Cross-sectional study, in which 105 women with adnexal tumors and indication for laparotomy/laparoscopy were included. All women were treated at a teaching hospital in the state of São Paulo between November 2009 and March 2011. All patients underwent a structured interview about the occurrence of 18 symptoms associated with ovarian cancer. The interview included the severity, frequency, and duration of these symptoms in the 12 months prior to the first medical consultation. The CA125 levels and the ultrasound classification of the tumors were also evaluated. We calculated for each symptom the prevalence ratio with 95% confidence intervals. The golden-standard was the result of the pathological examination of the surgical specimens. RESULTS: Of the 105 women included, 75 (71.4%) had benign tumors and 30 (28.6%) had malignant ones. In women with malignant tumors, the most frequent symptoms were: abdominal bloating (70%), increased abdominal size (67%), pelvic pain (60%), menstrual irregularity (60%), swelling (53%), abdominal pain (50%), backache (50%), and early repletion (50%). Women with benign tumors showed essentially pelvic pain (61%), menstrual irregularities (61%), and abdominal swelling (47%). Symptoms significantly associated with malignancy were: bloating (PR=2.0; 95%CI 1.01 - 3.94), increased abdominal size (PR=2.16; 95%CI 1.12 - 4.16), backache (RP=1.97; 95%CI 1.09 - 3.55), swelling (PR=2.25; 95%CI 1.25 - 4.07), early repletion (RP=2.06; 95%CI 1.14 - 3.70), abdominal mass (PR=1.83; 95%CI 1.01 - 3.30), eating difficulties (PR=1.98; 95%CI 1.10 - 3.56), and postmenopausal bleeding (PR=2.91; 95%CI 1.55 - 5.44). The presence of pelvic pain, constipation, dyspareunia, fatigue, abdominal pain, nausea or vomiting, menstrual irregularity, weight loss, diarrhea, and bleeding after intercourse was similar in both groups. CONCLUSIONS: In women with adnexal tumors including indication of surgical treatment, the preoperative evaluation of symptoms may help predicting malignancy.

Factors associated with HPV persistence after treatment for high-grade cervical intra-epithelial neoplasia with large loop excision of the transformation zone (LLETZ).

BACKGROUND AND OBJECTIVE: Human Papillomavirus (HPV) persistence after high-grade cervical intra-epithelial neoplasia (CIN) removal may be associated with residual lesions or risk of disease recurrence. Knowledge regarding the factors associated with HPV persistence following CIN treatment is still limited. The main purpose of this longitudinal study was to assess the association between characteristics of the patients and their cervical lesions with high-risk HPV-type persistence, detected by commercially available Hybrid Capture II (HC II), after CIN 2 and 3 treatment with large loop excision of the transformation zone (LLETZ). STUDY DESIGN: For this cohort study, a total of 94 women submitted to LLETZ between March 2001 and September 2002 were included. Only women with at least one follow-up visit at 6 or 12 months and confirmed CIN 2 or 3 in the cone specimen were considered. In each visit women answered to a questionnaire and undertook Pap smear and HC II specimens collection. McNemar's, chi-square and Fisher tests were used for univariate analysis. Generalized Estimating Equations (GEE) were used for multivariate analysis. All calculations were performed within 95% confidence intervals (95% CI). RESULTS: Histological evaluation showed 12 (13%) women with CIN, 2 and 82 (87%) with CIN 3 and conization margins were compromised in 27 (29%) cases. Eighty-seven (92%) women showed positive HC II tests prior to LLETZ. Of women initially HPV negative, none had a positive HC II during follow-up. The proportion of positive HPV tests was reduced from 92% to 20%(P < 0.01) at the first visit and to 22% (P < 0.01) at the second visit after LLETZ. Multivariate analysis showed that smoking and age above 35 years (irrespective of margin status) were strongly associated with positive HPV during follow-up. CONCLUSION: HPV persistence following LLETZ was associated with smoking and with the interaction between age and conization margins.