Malignancy-related ascites: Diagnostic and therapeutic strategies

Malignancy-related ascites, a frequent cause of significant morbidity and distress in many cancer patients, is often a marker of poor prognosis. Malignancies, mainly cancers of the colon, breast, ovary, endometrium, pancreas and stomach, account for nearly 10% of all cases of ascites. Between 10-15% of gastrointestinal cancer patients can develop ascites as a part of their disease course; the ascites are frequently recurrent and difficult to manage. The pathogenesis is multifactorial including both an increased production and a decreased clearance of peritoneal fluid. Cancer cells responsible for ascites formation can invade lymphatic channels or hepatic veins resulting in mechanical obstruction and fluid accumulation. Decreased lymphatic drainage can also result in intravascular volume depletion, which in turn activates renin-angiotensin-aldosterone system and causes sodium and fluid retention. Additionally, cancer cells also show increased expression of vascular endothelial growth factor (VEGF) and vascular permeability factor, which may lead to increased microvascular permeability. Patients with malignant ascites frequently present with signs and symptoms of underlying malignancy and features of elevated intra-abdominal pressure such as abdominal distension, anorexia, nausea, and dyspnea. Malignant ascites, particularly related to peritoneal carcinomatosis, can contribute to bowel obstruction, decreased oral intake and cachexia. The presence of ascites can be diagnosed using clinical and imaging modalities, however, ascitic fluid analysis is needed to differentiate malignant from benign causes. Cytologic analysis remains the gold standard for diagnosis despite its poor sensitivity. Individual tumor markers in ascitic fluid such as carcinoembryogenic antigen, cancer antigen 125 or carbohydrate antigen 19-9 have modest sensitivity; however, a combination of tumor markers may serve as an adjunct to cytology. Additionally, higher levels of fibronectin, cholesterol, sialic acid and telomerase activity in the ascitic fluid have shown excellent specificity and varying sensitivity for the diagnosis of malignant ascites; these tests can potentially be useful in the future to differentiate between malignant and benign ascites. The management of malignant ascites can be complex and should incorporate cancer-directed therapies in suitable patients. However, with malignant ascites frequently indicating the terminal stage of malignant process, the management is mostly palliative and consists of the use of diuretics, paracentesis, peritoneovenous shunts and intraperitoneal chemotherapy. All these strategies have shortcomings, and improved therapies are warranted. Novel treatments such as VEGF inhibitors, matrix metalloproteinase inhibitors and monoclonal antibodies have shown promising results but remain investigational.