Endometriosis peritoneal masiva asociada a gran elevación de CA-125: discrepancia entre hallazgos y clínica / Massive peritoneal endometriosis associated with high elevation of CA-125: discrepancy between findings and symptoms

ANTECEDENTES: Frecuentemente, las pacientes con endometriosis presentan una elevación de marcadores tumorales Ca 125 y Ca 19.9. No obstante, no existe correlación clara con la expresión clínica ni con el grado de afectación. En algunos casos, es necesario un diagnóstico diferencial con patologías malignas. CASO CLÍNICO: Mujer de 29 años con clínica aislada de dismenorrea moderada y hallazgo de masas ováricas bilaterales con elevación intensa de marcadores tumorales: Ca-125: 7.716 U/mL y Ca-19.9: 995 U/mL. Se decide intervención quirúrgica laparoscópica evidenciándose endometriosis ovárica y extensión peritoneal masiva con afectación de peritoneo parietal abdominal, superficie uterina, fondo de Douglas, parametrios, vejiga, hemidiafragma derecho, hígado y serosa intestinal. Se realiza adhesiolisis cuidadosa, quistectomía y extirpación de múltiples implantes endometriósicos en cavidad abdominal. Se observó un descenso de los marcadores a las 48 horas: Ca-125 de 253 U/mL y Ca 19.9 de 4,9 U/mL, ambos negativos al mes de la cirugía. CONCLUSIÓN: Una elevación intensa de los marcadores tumorales precisa de diagnóstico diferencial en el contexto de la endometriosis. Existe una gran discrepancia entre los valores de los marcadores tumorales con la clínica y severidad de la endometriosis. Los hallazgos quirúrgicos son fundamentales, evidenciando una afectación masiva subdiagnosticada hasta la cirugía.

BACKGROUND: Frequently, patients with endometriosis present elevated tumor marker Ca 125 and Ca 19.9. However, there is no clear correlation with the clinical expression or the degree of involvement. In some cases, differential diagnosis is necessary with malignancies. CASE REPORT: A 29 year old woman with moderate dysmenorrhea and finding of bilateral ovarian masses with intense elevation of tumor markers, CA125: 7,716 U/mL and Ca-19.9: 995 U/mL. Laparoscopic surgery is decided evidenced massive ovarian endometriosis and peritoneal extension with involvement of abdominal peritoneum, uterine surface, Douglas, parametrium, bladder, right hemidiaphragm, liver and intestinal serosa. Careful liberation of adherences, ovarian cystectomy and removal of multiple endometriosic implants. A decrease of tumor markers was observed at 48 hours (Ca-125: 253 U/mL and Ca-19.9: 4.9 U/mL), and negative one month after surgery. CONCLUSION: An intense elevated tumor markers accurate differential diagnosis in the context of endometriosis. There is a large discrepancy between the values of tumor markers with clinical and severity of endometriosis.

Benefits of a Continuous Ambulatory Peritoneal Dialysis (CAPD) Technique with One Icodextrin-Containing and Two Biocompatible Glucose-Containing Dialysates for Preservation of Residual Renal Function and Biocompatibility in Incident CAPD Patients

In a prospective randomized controlled study, the efficacy and safety of a continuous ambulatory peritoneal dialysis (CAPD) technique has been evaluated using one icodextrin-containing and two glucose-containing dialysates a day. Eighty incident CAPD patients were randomized to two groups; GLU group continuously using four glucose-containing dialysates (n=39) and ICO group using one icodextrin-containing and two glucose-containing dialysates (n=41). Variables related to residual renal function (RRF), metabolic and fluid control, dialysis adequacy, and dialysate effluent cancer antigen 125 (CA125) and interleukin 6 (IL-6) levels were measured. The GLU group showed a significant decrease in mean renal urea and creatinine clearance (-Delta1.2+/-2.9 mL/min/1.73 m2, P=0.027) and urine volume (-Delta363.6+/-543.0 mL/day, P=0.001) during 12 months, but the ICO group did not (-Delta0.5+/-2.7 mL/min/1.73 m2, P=0.266; -Delta108.6+/-543.3 mL/day, P=0.246). Peritoneal glucose absorption and dialysate calorie load were significantly lower in the ICO group than the GLU group. The dialysate CA125 and IL-6 levels were significantly higher in the ICO group than the GLU group. Dialysis adequacy, beta2-microglobulin clearance and blood pressure did not differ between the two groups. The CAPD technique using one icodextrin-containing and two glucose-containing dialysates tends to better preserve RRF and is more biocompatible, with similar dialysis adequacy compared to that using four glucose-containing dialysates in incident CAPD patients. [Clincal Trial Registry, ISRCTN23727549]

Benefits of a Continuous Ambulatory Peritoneal Dialysis (CAPD) Technique with One Icodextrin-Containing and Two Biocompatible Glucose-Containing Dialysates for Preservation of Residual Renal Function and Biocompatibility in Incident CAPD Patients

In a prospective randomized controlled study, the efficacy and safety of a continuous ambulatory peritoneal dialysis (CAPD) technique has been evaluated using one icodextrin-containing and two glucose-containing dialysates a day. Eighty incident CAPD patients were randomized to two groups; GLU group continuously using four glucose-containing dialysates (n=39) and ICO group using one icodextrin-containing and two glucose-containing dialysates (n=41). Variables related to residual renal function (RRF), metabolic and fluid control, dialysis adequacy, and dialysate effluent cancer antigen 125 (CA125) and interleukin 6 (IL-6) levels were measured. The GLU group showed a significant decrease in mean renal urea and creatinine clearance (-Delta1.2+/-2.9 mL/min/1.73 m2, P=0.027) and urine volume (-Delta363.6+/-543.0 mL/day, P=0.001) during 12 months, but the ICO group did not (-Delta0.5+/-2.7 mL/min/1.73 m2, P=0.266; -Delta108.6+/-543.3 mL/day, P=0.246). Peritoneal glucose absorption and dialysate calorie load were significantly lower in the ICO group than the GLU group. The dialysate CA125 and IL-6 levels were significantly higher in the ICO group than the GLU group. Dialysis adequacy, beta2-microglobulin clearance and blood pressure did not differ between the two groups. The CAPD technique using one icodextrin-containing and two glucose-containing dialysates tends to better preserve RRF and is more biocompatible, with similar dialysis adequacy compared to that using four glucose-containing dialysates in incident CAPD patients. [Clincal Trial Registry, ISRCTN23727549]

Dosagem do antígeno ca125 para acompanhamento de tratamento e seguimento pós-tratamento de neoplasia maligna epitelial de ovário / Dosage of ca125 antigen for treatment follow-up and post-treatment follow-up of malignant ovarian epithelial neoplasia

O carcinoma de ovário é a neoplasia maligna ginecológica mais letal, com incidência mundial de 200.000 novos casos a o ano. Dados internacionais estimam que cerca de 75% dos novos diagnósticos são realizados em estágios avançados, o que é responsável, em parte, pela alta mortalida de associada. Cerca de 90% dos carcinomas de ovário são de origem epitelial, da superfície epitelial ovariana ou derivados mullerianos, como as tubas uterinas (trompas de Falópio). Os adenocarcinomas primários peritoneais são classificados e tratados como carcinomas ovarianos epiteliais. Os demais tumores ovarianos derivam de outras células, como as germinativas, estromais ou mistas, e não serão abordados, por apresentarem comportamento e tratamentos distintos. O Antígeno CA 125: Evoluindo das enzimas ou hormônios, tem-se verificado, nas duas últimas décadas, um aumento do número dos chamados marcadores tumorais (substâncias circulantes, substâncias celulares, receptores de membrana celular, índices celular e nuclear, células, genes e expressões genéticas), cuja validade ou se consolidou como definitiva ou se inutilizou por ineficaz. Essa evolução se deu não só em termos de métodos laboratoriais (por exemplo, a gonadotrofina coriônica humana (hCG) medida na urina de 24 horas substituída pela dosagem sérica da fração beta dessa gonadotrofina (beta-hCG), como marcador de neoplasia de origem trofoblástica ou germinativa), mas também de elementos (a proteinúria de Bence-Jones substituída pela eletroforese de imunoglobulinas, como marcador de neoplasia de células plasmáticas) e mesmo de estruturas nucleares (o cromossoma Philadelphia e o gene bcr-abl, em casos de leucemia mielóide crônica). O CA 125 é um dos marcadores tumoral que ainda têm um papel questionável em neoplasia maligna epitelial de ovário. Alterações nos seus níveis séricos podem ser utilizadas como uma indicação de resposta terapêutica ou de progressão tumoral, mas ele não tem uma clara função na detecção, no diagnóstico ou no prognóstico desta neoplasia. Aproximadamente 50% das doentes de câncer de ovário que têm dosagens séricas normais de CA 125 persistem com tumor residual ao final da terapia. O CA 125 tem sua validade restrita à avaliação da resposta terapêutica e da progressão tumoral, em casos de diagnóstico confirmado de neoplasia maligna epitelial de ovário ou de tuba uterina sob tratamento antineoplásico. O Diagnóstico e estadiamento do câncer de ovário frequentemente se manifesta em estágios avançados, com a ocorrência de sintomas vagos, como distensão abdominal, dor abdominal ou pélvica, sintomas urinários, surgimento de massa abdominal, flatulência ou saciedade precoce relacionada a metástases peritoneais. Em alguns casos, pode ocorrer dispneia devido à ascite ou a derrame pleural associado. Os sintomas inicialmente não levam de imediato à suspeita de câncer. Sua evolução e persistência em mulheres entre 40 e 65 anos, faixa etária na qual a incidência torna-se mais frequente, pode levar o médico a suspeitar e diagnosticar esta neoplasia. O Diagnóstico laboratorial dos carcinomas epiteliais de ovário podem ser responsáveis pela produção do marcador tumoral CA 125. Esta glicoproteína pode estar presente em concentrações elevadas em pacientes com câncer de ovário, porém isoladamente não é útil como exame de triagem ou diagnóstico, podendo ser válido para o acompanhamento das pacientes em tratamento antineoplásico e durante seu seguimento. Monitorização do Tratamento: Avaliação da resposta terapêutica: Após o término do tratamento primário para o câncer epitelial de ovário, é de interesse avaliar se houve resposta completa (RC) por tomografia abdominal total e, no caso de doença metastática extra- abdominal pré-existente, tomografia também de tórax. O uso do marcador CA 125 é amplamente difundido como avaliação de resposta e doença persistente. Entretanto, cerca de 50% das pacientes com valores normais de CA 125 após a quimioterapia apresentam doença residual se avaliadas por cirurgia de second look. Estimativa do Impacto Orçamentário: A incorporação de um procedimento específico para a dosagem do CA 125, para acompanhamento de doentes de neoplasia maligna epitelial de ovário ou de trompa uterina ou de carcinomatose peritoneal, sob tratamento antineoplásico, não traria impacto financeiro para o SUS e orientaria uma melhor utilização deste marcador. Recomendação da CONITEC: Os membros da CONITEC presentes na 7ª reunião ordinária do dia 02/08/2012 recomendaram a incorporação da dosagem do antígeno CA125 para acompanhamento de tratamento e seguimento pós-tratamento de neoplasia maligna epitelial de ovário, conforme Diretrizes Diagnósticas e Terapêuticas (DDT) a ser elaborada pelo Ministério da Saúde. A Portaria CTIE/MS Nº37, de 27 de dezembro de 2012 - Torna pública a decisão de incorporar a dosagem do antígeno CA125 para acompanhamento de tratamento e seguimento pós-tratamento de neoplasia maligna epitelial de ovário no Sistema Único de Saúde.

correlation between serum and peritoneal fluid CA125 level in women with pelvic endometriosis

Despite a high prevalence of endometriosis, there still exist many challenges in diagnosing the disease. This study aims to evaluate non-invasive and practical diagnostic methods by measuring serum and peritoneal fluid CA 125 levels in patients with endometriosis. A secondary aim is to determine the correlation between these markers with the stage of disease as well as the relationship of the two markers with each other. This is a cross-sectional study of 60 women who underwent laparoscopy for benign conditions. Based on laparoscopic findings and biopsy results, patients were divided to two groups; one group included patients with pelvic endometriosis [35 patients] and the second enrolled patients free from endometriosis [25 patients]. Serum and peritoneal fluid specimens were provided at the time of laparoscopy and CA125 levels were then assessed by electrochemiluminescence immunoassay. Mean serum and peritoneal fluid CA125 levels were significantly higher in women with endometriosis as compared to the control group [26.42 +/- 24.34 IU/ml versus 12.64 +/- 6.87 IU/ml in serum and 2203.54 + 993.19 IU/ml versus 1583.42 +/- 912.51 IU/ml in peritoneal fluid, p<0.05]. CA 125 levels also varied proportionally with the stage of endometriosis; but showed a significant difference only in higher stages of the disease, both in serum and peritoneal fluid. We calculated the cut-off value suggesting a diagnosis of pelvic endometriosis as 14.70 IU/ml for serum and 1286.5 IU/ml for peritoneal fluid CA125. A linear correlation between CA 125 levels in serum and peritoneal fluid in patients with pelvic endometriosis has also been observed. Serum and peritoneal fluid CA 125 levels are simple and non-surgical tools for diagnosing and staging pelvic endometriosis. These markers are of greater diagnostic value in higher stages of the disease

Step by step clinical diagnosis

A 54-year-old woman Para 5 was admitted to the hospital because of increasing abdominal enlargment. She felt well until a year ago, when abdominal distention gradually developed. In abdominal ultrasongraphy a coarse, echogenic liver and ascites was detected, the spleen was enlarged and other intraabdominal organs were normal. Abdominal paraeentesis was performed. Serum-aseites albumin gradient was greater than 1.1 gr/dl [high serum-ascites albumin gradient]. Laboratory-tests for evaluating the etiology of cirrhosis revealed: HBs Ag: Neg, HBc Ab: Neg, Hcv Ab: Neg, Anti HBs: Pos. ASMA [anti smooth muscle antibody]: Neg ANCA [anti neutrophilic cytoplasmic antibody]: Neg ANA [anti nuclear antibody]: Neg AMA [anti mitochondria! Antibody]: Neg SPEP [serum protein electrophoresis]: Normal range The patient had no history of hepatotoxic drug usage. In upper GI endoscopy two columns grade II varicose veins were seen. Based on the history and para clinic evaluation cryptogenic cirrhosis was the most probable diagnosis. The patient underwent medical therapy with furosemide and spironolactone, and in regular follow up amount of ascites was under control. A month ago the amount of ascites increased and several therapeutic paraeentesis were performed. Ascites analysis showed high serum-ascite albumin gradient and negative cytology for malignancy. Ultrasonography reported multiple focuses on peritoneal surface with seeding like appearance, cirrhotic liver, enlarged spleen and massive ascites, normal kidneys and uterus and ovaries.Tumour markers measurement revealed: CEA= 0.3 [Normal range= 0-5 ng/ml] alpha FP= 0.4 [Normal range= 0-10 lU/ml]CA 125- 244 [Normal range- 0-35 lU/ml] Abdominal and pelvic CT scan didn't show any tumoural lesion and no paraaortic lymphadenopathy. Trans vaginal sonography reported normal uterus and ovaries. Further tumour marker analysis revealed: Elevated serum level of CA 125 to 414 lU/ml CA 15 - 3 = 27 [normal = up to 40 lU/ml] CA 19 - 9 = 25 [normal = up to 40 lU/ml]. A week later level of CA 125 decreased to 262. Therefore we obtained fluctuating level of CA 125, normal CT scan and normal level of other tumour markers. We found in papers from other countries in the same situation that they performed laparotomy but they found nothing except cirrhosis [1]. In some articles CA 125 presented as a marker of ascites in patients with liver cirrhosis [2]. Some authors suggested that quantification of CA 125 in peritoneal fluid [PCA125] and serum [SCA125] can differentiate between cancer cases and non cancer disease, and they found that ratio of PCA125 to SCA125 [P/S CA125] was significantly lower in non cancer patients than that in cancer ones. [If the ratio is upper than five the risk of malignancy increased] [3]. We quantified CA125 level simultaneously in peritoneal fluid and serum: PCA125 - 210, SCA125 = 250, P/S CA125 - 0.84. The ratio of 0.84 was predictive of a benign disease. In an overview to our patient, we had one sonography that reported seeding like appearance in peritoneal surface, but in CT scan no lesion was detected. Fluctuating level [increase - decrease] of CA125 and low P/S ratio, normal level of other tumour markers, made us to come to the final step of laparoscopic examination and biopsy to determine whether it is malignant or benign. In laparoscopic examination no cancerous lesion or fibrin deposit or tuberculosis granoluma with normal omentum and cirrhotic liver detected. Multiple biopsies were taken from peritoan beside liver which reported normal [no: 159104]. We came to this conclusion that in cirrhotic patient with ascites the elevated level of CA125 with normal level of other tumour markers and low P/S ratio and no malignant finding in imaging is suggestive of a benign process, as described in other articles. More studies on this matter should be performed in order to prevent the unnecessary laparatomies

Role of cancer antigen-125 from pleural & ascitic fluid samples in non malignant conditions.

BACKGROUND & OBJECTIVE: CA-125, an ovarian tumor marker is known to increase in non malignant conditions such as tubercular and non tubercular pleuritis and ascites. We undertook this study to evaluate non-specific rise in CA-125 levels in conditions associated with pleural effusion and ascites and also to understand the mechanism of its secretion. METHODS: CA-125 levels in 38 pleural and 46 ascitic fluid samples from non malignant cases and 10 blood samples from pulmonary tuberculosis cases were estimated by ELISA. The ascitic fluid samples were collected from cases of bacterial peritonitis, tuberculosis, hepatitis, cirrhosis of other aetiology and pleural fluid samples were from cases of tubercular, pyogenic, cardiomegaly and other conditions. RESULTS: Both ascitic and pleural fluid samples (transudative and exudative) showed elevated CA- 125 levels. The CA-125 levels were significantly higher in ascitic fluid samples than in pleural fluid samples. INTERPRETATION & CONCLUSION: Our findings showed that elevated levels of CA-125 in pleural and ascitic fluid could be because of varied aetiologies which need to be ruled out before considering malignancy. Peritoneum has a greater capacity to secrete CA-125 than the pleural epithelium and the secretion occurs following inflammation or mechanical distress. Pulmonary tuberculosis as a closed lesion without involvement of pleural epithelium does not evoke high CA-125 release.

Neoadjuvant chemotherapy followed by surgical cytoreduction in advanced epithelial ovarian cancer.

AIMS: To study the role of neoadjuvant chemotherapy (NACT) followed by surgical cytoreduction in the management of advanced epithelial ovarian cancers. MATERIALS AND METHODS: A retrospective analysis of 82 patients with advanced epithelial ovarian cancers (stage IIIC and IV) who were treated with NACT followed by surgical cytoreduction between 1995 and 2004 was performed. Response to NACT, optimal cytoreduction rate, disease-free survival and overall survival were analyzed. RESULTS: There were 59 patients (72%) with stage IIIC disease and 23 (28%) with stage IV disease. Diagnosis was established by imaging, ascitic fluid cytology and CA-125 estimations in 75% and by laparotomy in 25% of the patients. After NACT, complete response occurred in 17 patients (20.7%), 50 (61.0%) had partial response and no response was documented in 15 (18.3%) patients. Optimal surgical cytoreduction could be achieved in 72% of the patients. At the median follow-up of 34 months (range 6-102 months), 5-year disease-free and overall survivals were 31 and 32% respectively. The median disease free interval was 25.4 months. On multivariate analysis, degree of optimal cytoreduction was the only factor (P < 0.05) affecting survival. CONCLUSIONS: NACT followed by surgical cytoreduction is a promising treatment strategy for the management of advanced epithelial ovarian cancers. A significant number of patients exhibit response to NACT. Downstaging following NACT leads to higher optimal cytoreduction rates and improved survival in comparison to historical controls.

Comparison of ultrasound score, CA125, menopausal status, and risk of malignancy index in differentiating between benign and borderline or malignant ovarian tumors.

OBJECTIVES: To evaluate the diagnostic performances of ultrasound score (US), CA 125, menopausal status, risk of malignancy index (RMI)-- in differentiating between benign and borderline or malignant ovarian tumors. MATERIAL AND METHOD: Women with ovarian masses who were scheduled to have elective surgery at the Department of Obstetrics and Gynecology, BMA Medical College and Vajira Hospital between May 1999 and December 2001 were included in the study. Ultrasonographic study and CA 125 were examined preoperatively. The RMI was obtained from the ultrasound score, CA 125, and menopausal status. The diagnostic values of each parameter and the RMI were determined. RESULTS: From 175 women, 35 women (20%) had malignant ovarian tumors. RMI yielded better diagnostic performance to differentiate between benign and borderline or malignant ovarian tumors than US score, CA 125, and menopausal status in respective order The optimal RMI to predict malignancy was 0.135 with the sensitivity of 88.6% (95% CI; 81.1%-96.1%), specificity of 90.7% (95% CI; 83.9%-97.6%), positive and negative predictive value of 70.5% (95% CI; 59.7%-81.2%) and 97.0% (95% CI; 92.9%-100.0%) respectively. CONCLUSION: RMI yielded better diagnostic performance than the individual parameter of ultrasound score, CA 125, or menopausal status in differentiation of benign from borderline or malignant ovarian tumors.

The Usefulness of CDX-2 for Differentiating Primary and Metastatic Ovarian Carcinoma: An Immunohistochemical Study Using a Tissue Microarray

Distinguishing primary ovarian carcinoma from metastatic carcinoma to the ovary is often difficult by histologic examination alone. Recently an immunohistochemical marker CDX-2 was found to be of considerable diagnostic value in establishing the gastrointestinal origin of metastatic tumors. The aim of this study was to determine whether CDX-2 can distinguish between these malignancies. Paraffin-embedded tissue sections from 57 primary ovarian tumors and 40 metastatic tumors to the ovary were immunostained for CDX-2, and results were compared to the ancillary immunohistochemical results for CK7/CK20, CEA, CA125, and her-2/neu. CDX-2 immunoreactivity was observed in most of metastatic carcinomas with colorectal (91%) and appendiceal (100%) origin, however CDX-2 was negative in all primary ovarian carcinomas, except for the mucinous subtype. Almost all primary ovarian carcinomas including the mucinous subtype showed diffuse and strong immunoexpression for CK7. CEA and CA125 were mainly found in metastatic and primary ovarian carcinoma, respectively. Her-2/neu overexpression was only noted in a small proportion of primary and metastatic ovarian carcinomas. These results suggest that CDX-2 is very useful immunohistochemical marker for distinguishing metastatic colorectal carcinoma to the ovary from primary ovarian carcinoma, including the mucinous subtype. Furthermore, combination with CDX-2 and CK7 strengthen the differential diagnosis between these tumors.

Evaluation of CA 125 tumor marker in patients with ovarian carcinoma

The mean value of CA 125 tumor marker in the sera of ovarian cancer patients was found to be ten times higher than that detected in the control group [normal individuals, patients with benign ovarian tumor and those with non-ovarian gynecologic malignancies]. Histologically, the major distribution of elevated values of CA 125 antigen was observed in secondary ovarian metastasis and those with epithelial ovarian tumors, respectively. The incidence of abnormal values of CA 125 was also increased with advanced stages of the disease. An elevated preoperative value of CA 125 [> 300 micro/ml] was able to predict poor prognosis while low concentrations [< 100 micro/ml] suggested early detection of the disease. All patients with ovarian carcinoma had positive abnormal concentrations of CA 125 in their sera [100% sensitivity]. In the control group only 20% of the women gave false positive values of CA 125 [80% specificity]. Such combination of sensitivity and specificity for CA 125 antigen was superior to other tumor markers