Definition, etiopathogenesis, management and role of flouroquinolone prophylaxis in prevention of spontaneous bacterial peritonitis complicating malignant ascites

Abstract

Background: Malignancy related ascites encompasses multiple etiologies which include peritoneal carcinomatosis, hepatic synthetic dysfunction due to parenchymal involvement by the tumour, transcoeloemic metastasis and chylous ascites due to lymphatic obstruction. Primary Cancer type, liver metastasis and serum albumin have been listed as independent prognostic markers in malignant ascites. Spontaneous Bacterial Peritonitis is usually seen as a complication of decompensated chronic liver disease due to translocation of bacteria or haematogenous dissemination from a distant focus of infection. The combination of a positive peritoneal fluid culture and an ascitic fluid neutrophil count >250 cells/mm3 and no evidence of intra-abdominal source of infection; or 2) culture negative neutrocytic ascites: the combination of negative peritoneal fluid bacterial culture and neutrophil count >500 cells/mm3, without antibiotics within 7 days with no obvious source of infection are used to define spontaneous bacterialperitonitis. Ciprofloxacin prophylaxis has been proposed as a prophylaxis to reduce the incidence and prevent the recurrence of spontaneous bacterial peritonitis. Materials and Methods: A web search of indexed literature was carried out articles containing information on spontaneous bacterial peritonitis in the setting of malignancy or malignancy related ascites or malignant ascites. Articles that carried relevant information about etiopathogenesis, management and translational research in the context of malignant ascites were also included. Results: A total of 32 articles were analysed and about half of them included in the discussion to answer the research question. Discussion: Inflammatory cytokines released by tumor and immune cells compromise the mesothelial cell layer that lines the peritoneal cavity, exposing the underlying extracellular matrix to which cancer cells readily attach leading to formation of spheroids which imparts resistance to anoikis, apoptosis and chemotherapeutics leading to efficient feed forward progressive cycle of seeding and growth of peritoneal metastasis. Intraperitoneal metastasis can cause peritoneal dysfunction, adhesions and malignant ascites. Epithelial mesenchymal transistion and myofibroblastic transformation occur in the mesothelial cells in response to pathological stimuli. Vascular endothelial growth factor is an important mitogen for endothelial cells and plays an important role in increasing capillary vascular permeability. In preclinical studies systemic administration of VEGF Trap which acts as a decoy receptor for VEGF has shown to decrease the formation of ascites fluid and prevent tumour dissemination. Epithelial ovarian cancer cells have developed various mechanisms to evade immune surveillance like development of surface microvesicles which contain CD 95 ligand leading to apoptosis of immune cells. Higher levels of osteoproteogerin, IL 10 and leptin in the ascitic fluid have been associated with a poor prognosis in malignant ascites. Tethered bowel sign and presence of fluid in the omental bursa on CT have been shown to distinguish between malignant ascites and Cirrhotic ascites with accuracy. Immunological approaches to management of malignant ascites include use of intraperitoneal triamcinolone, interferon, long acting synthetic corticosteroids and the trifoliate antibody catumaxomab. VEGF Inhihibitors like octreotide and long acting depot preparations of lanreotide have also been shown to be feasible therapeutic options. Anti androgenic agents and PARP inhibitors have also been proposed as management options. Spontaneous bacterial peritonitis in the setting of malignancy in the absence of hepatic dysfunction has been reported to have a poorer prognosis than SBP in the setting of decompensated liver disease. Monomicrobial and polymicrobial bacterascites have been proposed in the absence of an elevated neutrophil ascitic fluid count that does not meet the diagnostic criteria. Extensive liver metastasis where the diseased liver can be expected to behave like a cirrhotic liver and gastrointestinal bleeding (on the basis of an isolated case report) have been considered as risk factors for the development of SBP in malignant ascites. In a case series of 8 patients with malignancy related ascites Patients with total ascitic fluid concentration of less than 1 gm per litre were found to be at risk for Spontaneous bacterial peritonitis and warrant flouroquinolone prophylaxis. Conclusion: Spontaneous Bacterial Peritonitis complicating malignant ascites is questionable entity. Good quality Audits and Randomised control trials are warranted to in this domain to enable the definition of incidence, antecedent complications, management and prophylaxis to ensure applicability of translational research to the clinical domain.