An ultra-sensitive impedimetric immunosensor for detection of the serum oncomarker CA-125 in ovarian cancer patients.

Effective treatment of ovarian cancer depends upon the early detection of the malignancy. Here, we report on the development of a new nanostructured immunosensor for early detection of cancer antigen 125 (CA-125). A gold electrode was modified with mercaptopropionic acid (MPA), and then consecutively conjugated with silica coated gold nanoparticles (AuNP@SiO2), CdSe quantum dots (QDs) and anti-CA-125 monoclonal antibody (mAb). The engineered MPA|AuNP@SiO2|QD|mAb immunosensor was characterised using transmission electron microscopy (TEM), atomic force microscopy (AFM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Successive conjugation of AuNP@SiO2, CdSe QD and anti-CA-125 mAb onto the gold electrode resulted in sensitive detection of CA-125 with a limit of detection (LOD) of 0.0016 U mL(-1) and a linear detection range (LDR) of 0-0.1 U mL(-1). Based on the high sensitivity and specificity of the immunosensor, we propose this highly stable and reproducible biosensor for the early detection of CA-125.

Índice de risco de malignidade para tumores do ovário incorporando idade, ultra-sonografia e o CA-125

OBJETIVOS: calcular a sensibilidade, a especificidade e a acurácia das variáveis: idade da paciente, aspecto ultra-sonográfico e dosagem do marcador CA-125 para o diagnóstico diferencial entre tumores malignos e benignos do ovário. Estabelecer, ainda, índice de risco de malignidade (IRM) com a incorporação dessas três variáveis e calcular a sua sensibilidade, especificidade e acurácia para aquele diagnóstico diferencial. MÉTODOS: foram incluídas prospectivamente 100 pacientes portadoras de tumor do ovário com indicação cirúrgica. As variáveis idade, resultado da ultra-sonografia e níveis do CA-125 foram avaliadas isoladamente e depois em conjunto, sob a forma de índice (IRM). O estudo compreendeu a avaliação da sensibilidade, da especificidade e da acurácia diagnóstica e a aplicação das medidas: razão de probabilidade, razão de chances e dos testes: t de Student, chi² e regressão logística com análise uni e multivariada. RESULTADOS: para a variável idade, a sensibilidade, a especificidade e a acurácia diagnóstica foram respectivamente 58,8, 68,2 e 65,0%. Para a ultra-sonografia, 88,2, 77,3 e 81,0%. Para a dosagem do CA-125 esses valores foram 64,7, 74,2 e 71,0%. Quando as três variáveis foram agrupadas sob a forma do IRM observou-se sensibilidade de 76,5%, especificidade de 87,9% e acurácia diagnóstica de 84,0%. CONCLUSÕES: o IRM constituído pela associação das variáveis idade da paciente, resultado da ultra-sonografia e dosagem do CA-125 é indicador valioso para se distinguir entre tumores malignos e benignos de ovário, principalmente no que diz respeito à sua especificidade.

Correlação entre os níveis de Ca-125 séricos e os achados cirúrgicos em mulheres com sintomas sugestivos de endometriose

OBJETIVO: Correlacionar os níveis séricos pré-operatórios do antígeno do câncer 125 (Ca-125) e os achados laparoscópicos em mulheres com sintomas dolorosos sugestivos de endometriose. MÉTODOS:Um estudo retrospectivo foi realizado incluindo todas as mulheres com sintomas de dor pélvica suspeitos para endometriose operadas por laparoscopia no período de janeiro de 2010 a março de 2013. As pacientes foram divididas em 2 grupos de acordo com a dosagem de Ca-125 (<35 U/mL e >35 U/mL). Subsequentemente, as pacientes com endometrioma ovariano foram excluídas e uma análise adicional foi conduzida novamente de acordo com os níveis do Ca-125. Os seguintes parâmetros foram comparados entre os grupos: presença de endometrioma, presença e número de lesões de endometriose profunda infiltrativa (EPI) e escore da American Society for Reproductive Medicine. A análise estatística foi realizada com o programa Statistica versão 8.0, usando o teste exato de Fisher, o teste t de Student e o teste Mann-Whitney, quando necessário. Os valores p<0,05 foram considerados estatisticamente significativos. RESULTADOS: Durante o período de estudo, um total de 350 mulheres foram submetidas a tratamento laparoscópico de endometriose. Cento e trinta pacientes (37,1%) apresentaram Ca-125 >35 U mL e 220 (62,9%) apresentaram Ca-125 <35 U/mL. A presença de endometrioma ovariano (47,7 versus 15,9%), lesões de EPI (99,6 versus 78,6%) e lesões de EPI intestinal (60 versus 30,9%) foi mais frequente, e o escore da AFSr foi maior (34 versus 6) no primeiro grupo. Na segunda análise, excluindo as pacientes com endometrioma ovariano (>35 U/mL=68 pacientes e <35 U/mL=185 pacientes), resultados semelhantes foram obtidos. A presença de lesões de EPI (91,2 versus 76,2%), lesões de EPI intestinal (63,2 versus 25,4%), lesões de EPI de bexiga (20,6 versus 4,8%) e lesões de EPI ureteral (7,3 versus 1,6%) foi mais frequente, e o escore da AFSr foi maior (10 versus 6) no grupo Ca-125>35 U/mL. CONCLUSÕES: Em mulheres com sintomas dolorosos pélvicos suspeitos para endometriose com dosagem pré-operatória de Ca-125 >35 U/mL, a investigação de EPI é mandatória, especialmente quando não se identifica endometrioma ovariano em exames de imagem.

Myxedema ascites with elevated serum CA 125 concentration

We report a case of myxedema ascites and markedly elevated serum CA 125 concentration. The cause of ascites and elevated tumor markers in hypothyroidism remains unknown. Diagnosis was characterized by no evidence of malignancy seen by transvaginal ultrasonography or abdominal computed tomography and ascites resolution with serum CA 125 normalization after adequate hormonal treatment. Our data suggest that hypothyroidism should be considered in patients with ascites and elevated serum CA 125.

Evaluation of CA-125 and soluble CD-23 in patients with pelvic endometriosis: a case-control study

Objective: To evaluate serum concentrations of CA-125 and soluble CD-23 and to correlate them with clinical symptoms, localization and stage of pelvic endometriosis and histological classification of the disease. Methods: Blood samples were collected from 44 women with endometriosis and 58 without endometriosis, during the first three days (1st sample) and during the 7th, 8th and 9th day (2nd sample) of the menstrual cycle. Measurements of CA-125 and soluble CD-23 were performed by ELISA. Mann-Whitney U test was used for age, pain evaluations (visual analog scale) and biomarkers concentrations. Results: Serum levels Of CA-125 were higher in endometriosis patients when compared to the control group during both periods of the menstrual cycle evaluated in the study. This marker was also elevated in women with chronic pelvic pain, deep dyspareunia (2nd sample), dysmenorrhea (both samples) and painful defecation during the menstrual flow (2nd sample). CA-125 concentration was higher in advanced stages of the disease in both samples and also in women with ovarian endometrioma. Concerning CD-23, no statistically significant differences were observed between groups. Conclusion: The concentrations of CA-125 were higher in patients with endometriosis than in patients without the disease. No significantly differences were observed for soluble CD-23 levels between groups.

High serum follistatin levels in women with ovarian endometriosis

Follistatin is an activin-binding protein produced by several tissues, including endometrium and endometriotic implants. We aimed to quantify follistatin in patients with ovarian endometriosis and investigate its value as a diagnostic marker. Women undergoing laparoscopic excision of ovarian endometrioma (n = 52) or other benign ovarian cysts (n = 52) were studied, plus women with non-ovarian endometriosis (n = 11) and healthy controls (n = 27). Serum was collected from all subjects, and peritoneal and cystic fluid from a subset with endometrioma. Follistatin was measured by enzyme-linked immunosorbent assay. The diagnostic accuracy of follistatin to detect endometrioma was evaluated by receiver operating characteristic (ROC) curve and compared with cancer antigen (CA)-125. Serum follistatin was increased in women with ovarian endometrioma (2080 +/- 94 pg/ml) compared with controls (545 +/- 49 pg/ml, P < 0.001), other benign ovarian cysts (795 +/- 60 pg/ml, P < 0.001) or non-ovarian endometriosis (1271 +/- 115 pg/ml, P < 0.001). Cystic fluid showed a higher concentration of follistatin (9850 +/- 4461 pg/ml) than peritoneal fluid (1885 +/- 261 pg/ml, P < 0.001) and serum (P < 0.001). Follistatin levels detected 48/52 cases of endometrioma (92% sensitivity) at 1433 pg/ml cut-off, corresponding to 92% specificity. CA-125 detected only 44% of endometriomas with 90% specificity. ROC curve comparison showed follistatin was more accurate than CA-125 to discriminate women with endometrioma either from controls or women with other benign ovarian cysts (P < 0.0001). Serum follistatin is increased in women with endometriosis and allows clear distinction between endometrioma and other benign ovarian cysts. Follistatin has the sensitivity and specificity to become a useful clinical marker of ovarian endometrioma.

Primary adenocarcinoma of the fallopian tube as an incidental finding during surgery in a postmenopausal patient with unspecific pelvic pain

Primary fallopian tube carcinoma (PFTC) is a rare gynecologic neoplasm and is usually diagnosed late and presents classically with a,characteristic group of symptoms. We describe a case of a 76-year-old woman who underwent TVS requested by the family physician due to unspecific pelvic pain. An adnexal mass was found with morphology associated with high levels of CA125 suggestive of a malignant tumor. During laparotomy, a mass located in the left tube was found. Histopathology confirmed PFTC. Total hysterectomy, salpingo-oophorectomy and adjuvant chemotherapy with carboplatin/paclitaxel were performed. The patient has not yet presented any signs of recurrence.

Molecular imprinted nanoelectrodes for ultra sensitive detection of ovarian cancer marker

The relentless discovery of cancer biomarkers demands improved methods for their detection. In this work, we developed protein imprinted polymer on three-dimensional gold nanoelectrode ensemble (GNEE) to detect epithelial ovarian cancer antigen-125 (CA 125), a protein biomarker associated with ovarian cancer. CA 125 is the standard tumor marker used to follow women during or after treatment for epithelial ovarian cancer. The template protein CA 125 was initially incorporated into the thin-film coating and, upon extraction of protein from the accessible surfaces on the thin film, imprints for CA 125 were formed. The fabrication and analysis of the CA 125 imprinted GNEE was done by using cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) techniques. The surfaces of the very thin, protein imprinted sites on GNEE are utilized for immunospecific capture of CA 125 molecules, and the mass of bound on the electrode surface can be detected as a reduction in the faradic current from the redox marker. Under optimal conditions, the developed sensor showed good increments at the studied concentration range of 0.5–400 U mL−1. The lowest detection limit was found to be 0.5 U mL−1. Spiked human blood serum and unknown real serum samples were analyzed. The presence of non-specific proteins in the serum did not significantly affect the sensitivity of our assay. Molecular imprinting using synthetic polymers and nanomaterials provides an alternative approach to the trace detection of biomarker proteins.

Appendiceal Mucocele – Unexpected Diagnosis in a Gynecology Department

Appendiceal mucocele is a rare entity, occuring in < 1% among appendicectomies, with a female predominance 4/1 (F/M) and a mean age of more than 50 years. The preoperative diagnosis is difficult; in most cases, it´s an intraoperative finding. In such work, we describe the two clinical cases occurring in last 10 years in our Department. Case 1 - 56 years old, posmenopausal, referred to our Department (02/2004) because an asymptomatic right adnexal septated cystic image, 53x48mm, with hipovascularized septa and a vascularised capsule with low flow resistance (IR 0,57). CA 125 elevated (71,3 U/mL).Exploratory laparotomy: an ovary increased, with a gelatanious consistency and an appendicular enlargement. Extemporaneous examination: a pseudomixoma peritonei, associated with a mucinous appendicular and an ovary tumor. It was performed a radical surgery. The histo-pathological analysis showed a mucinous cystadenoma of the appendix with peritoneal mucinous dissemination involving the ovary. Expectant attitude since the surgery, without clinical and imaging signs of recurrence. Case 2- 62 years old posmenopausal and asymptomatic woman, with a large adnexal mass detected on routine pelvic ultrasound: heterogeneous, 94x84mm without vascularisation signs in its interior. CEA was elevated (41,47U/ml). Exploratory laparotomy (02/2010): enlarged appendix and macroscopically normal pelvic organs. An appendicectomy was performed. The histo-pathological analysis showed a 10cm mucinous cystadenoma of the appendix and signs of localized (visceral peritoneal surface) pseudomyxoma peritonei. Currently she’s clinically well, in an expectant attitude. Despite mucoceles of the appendix are rare, they should be considered in women presenting with abnormal quadrant masses.

Dépistage du cancer ovarien dans la population générale [Ovarian cancer screening in the general population].

Although the incidence of ovarian cancer is low, mortality from this cancer is high due to discovery at a late stage in the majority of cases. So it seems worthwhile to detect ovarian cancer at an early stage. The clinical presentation is nonspecific, thus screening tools have been evaluated. The most efficient screening technique includes two steps: evaluation of CA-125 and then sonography in case of abnormal results of CA-125. Two main studies have been performed in large populations. The PLCO-study has led to negative results: no reduction in ovarian cancer mortality in the screening group with an important increase in surgical morbidity. The final results of the UKCTOCS-study will be known in two years. Currently these data can't allow the realization of ovarian cancer screening in the general population, mainly due to their natural history.

Avaliação hormonal e de marcadores séricos em pacientes com abortamento

Estudos têm demonstrado a utilização de glicoproteínas e hormônios para prognosticar a evolução de uma gravidez complicada por ameaça de abortamento. Entretanto, alguns resultados ainda são duvidosos. Portanto, o objetivo deste estudo foi avaliar as dosagens de CA-125, CA-19.9, CA-15.3, beta-hCG, estradiol, progesterona, alfa-fetoproteína e antígeno cárcino-embrionário no sangue periférico de mulheres com abortamento inevitável (n=18) e com ameaça de abortamento que posteriormente evoluíram para o abortamento (n=6) no prazo de 1 a 26 dias. O grupo controle foi constituído de mulheres grávidas normais com idade gestacional semelhante (n=7). Todas as pacientes foram atendidas no Hospital Escola e/ou Ambulatório de Ginecologia e Obstetrícia da Faculdade de Medicina do Triângulo Mineiro. Os resultados demonstraram que as dosagens de CA-125 nos grupos controle, abortamento inevitável e ameaça de abortamento foram, respectivamente: 24,7 ± 13,4 UI/ml; 153,9 ± 43,3 UI/ml e 17,4 ± 2,6 UI/ml sendo estatisticamente significante a diferença entre o grupo com abortamento inevitável em comparação com os outros grupos. A dosagem de CA-19.9 foi significantemente menor no grupo com abortamento inevitável em relação ao grupo com ameaça de abortamento (6,6 ± 1,4 UI/ml versus 20,2 ± 11,4 UI/ml). A dosagem de estradiol foi significantemente menor no grupo com abortamento inevitável em comparação com o grupo controle (1.327 ± 1.015 ng/ml versus 10.774 ± 9.244 ng/ml). As pacientes com ameaça de abortamento e com abortamento inevitável apresentaram níveis mais baixos de progesterona que o grupo controle, respectivamente: 17,38 ± 9,4 ng/ml; 18,3 ± 8,9 ng/ml e 60,4 ± 26,8 ng/ml. Concluímos que as dosagens de progesterona, CA-19.9 e do beta-hCG podem servir como prognóstico de evolução de uma gravidez inicial complicada com ameaça de abortamento.

Tuberculose Pélvica Simulando Tumor Ovariano: a Case Report

A tuberculose pélvica é uma forma de tuberculose extrapulmonar cuja incidência vem aumentando no mundo ocidental. Esta entidade freqüentemente é acompanhada de achados clínicos e laboratoriais que podem ser inespecíficos e mimetizar outras doenças, inclusive neoplasias ginecológicas. Os autores apresentam um caso de tuberculose pélvica associada à tuberculose peritoneal do abdome em uma mulher de 53 anos, que foi submetida a avaliação laboratorial extensa, incluindo laparoscopia diagnóstica, dosagem de CA-125 e reação de Mantoux. Os aspectos clinicopatológicos e os meios propedêuticos para elucidar o caso são discutidos.