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Measurement of serum Ca 125 in the initial evaluation of a woman with ascites can lead to unnecessary investigations or even surgery.
A woman aged 56 was admitted with swelling of the lower limbs and the abdomen which had developed slowly. Previously she had been well; she had never smoked and drank little alcohol. Cytological and microbiological examination of ascitic fluid revealed nothing abnormal. An echocardiogram, however, showed dilated and poorly contracting cardiac chambers with moderate mitral and tricuspid regurgitation. Idiopathic dilated cardiomyopathy was diagnosed and the patient was started on diuretics and an angiotensin converting enzyme inhibitor.
In view of the gross ascites, serum Ca 125 was checked and proved to be greatly raised at 2150 IU/mL (normal <38). Although no malignant cells had been found in the ascitic fluid, a gynaecological opinion was sought. On vaginal examination, there were no adnexal masses palpable. A CT scan of the pelvis was normal. Transabdominal ultrasound revealed a normal right ovary but the left ovary was not clearly visualized. Because the cause of the raised serum Ca 125 remained unclear, exploratory laparotomy was decided upon. However, in the interim the patient responded to heart failure treatment with almost complete resolution of ascites and peripheral oedema. Serum Ca 125 fell to 240 IU/mL. Importantly, a transvaginal ultrasound showed normal ovaries. The laparotomy was therefore cancelled and the patient continued on heart failure treatment. When reviewed 2 months later, she was well and serum Ca 125 had returned to normal (31 IU/mL).
4 years later she returned with gross ascites and peripheral oedema. This time serum Ca 125 was 4020 IU/mL, but cytological and microbiological examination of ascitic fluid was again normal, as was a transvaginal ultrasound. She responded well to intravenous diuretics and fluid restriction. Maintenance doses of frusemide and enalapril were increased. 3 months later she was clinically euvolaemic and serum Ca 125 was normal.
In a postmenopausal female with ascites, raised serum Ca 125 is frequently perceived as a diagnostic marker of ovarian cancer. This is a misconception. Although the Ca 125 antigen is present on more than 80% of malignant epithelial ovarian tissue of non-mucinous type, it is also found on both healthy and malignant cells of mesothelial (pleural, pericardial, peritoneal, endometrial) and non-mesothelial (amniotic membrane, tracheobronchial and cervical epithelium) origin. Raised serum Ca 125 levels have therefore been reported in various conditions involving these cells, including pleural and pericardial effusions and ascites1.
The mechanism of raised serum Ca 125 in ascites is not fully understood. In culture, peritoneal mesothelial cells shed five times more Ca 125 than ovarian cancer cells2, and one theory is that the antigen enters the blood via lymphatic absorption of ascites3. Peritoneal stretching seems relevant, since serum Ca 125 falls rapidly after paracentesis4. In patients with cirrhosis an additional factor could be low clearance of Ca 125 by the liver5; and in those with malignant ascites, infiltration of the peritoneal membrane could contribute.
Serum Ca 125 is therefore a non-specific marker. Currently it is used for monitoring response to treatment and detection of recurrent disease in patients with known ovarian cancer6, and as an aid to differential diagnosis of adnexal masses7. Its value in screening for ovarian cancer is being investigated8.
Our case illustrates that, for good management decisions, a rational order of investigations is crucial. In this patient, during investigation of ascites, serum Ca 125 was measured before pelvic ultrasound examination. This happened on two occasions and, unfortunately, each time this led to diagnostic confusion and concerns about ovarian cancer. On the first occasion surgery was scheduled, and this would have been particularly hazardous in view of the true cause of the ascites.
The exclusion of metastatic ovarian cancer as a cause of ascites is of great importance in view of the benefits of chemotherapy in advanced disease9. We suggest that every woman with first-onset ascites should have a pelvic ultrasound scan (preferably transvaginal) unless lymphoma cells are found in the ascitic fluid. Although not specifically evaluated in patients with ascites, a normal pelvic ultrasound scan in a symptom-free postmenopausal woman with raised serum Ca 125 indicates an extremely low risk of ovarian cancer10. Pelvic ultrasound should also be considered in patients with an unexplained worsening of ascites the cause of which had been established previously. If an adnexal mass is identified, serum Ca 125 may be a useful diagnostic aid; in the absence of a mass, misinterpretation of a raised serum Ca 125 can lead to unnecessary and hazardous interventions.