Inflammatory patterns of ascites in patients with solid tumors

BackgroundAscites is a common complication in patients with solid tumors. Due to lacking pathophysiological insight treatment has not improved significantly. Recent evidence suggests that inflammation fosters ascites development in patients with tumors, which may be a potential target for novel treatment approaches.MethodsPatients with ascites due to solid tumors (n=54) and benign ascites due to liver cirrhosis (n=8) were included. Patients with peritonitis, defined as an absolute neutrophil count >0.25G/l were excluded from analysis. Cytokines were measured by a multiplex cytokine assay or ELISA in ascites and corresponding serum samples if available.ResultsAmong patients with solid tumors, 31 (57.4%) presented with negative cytology (paramalignant) and 23 (42.6%) with positive cytology (malignant). Tumors most commonly originated from the pancreas (27.8%), upper gastrointestinal tract (18.5%), breast (14.8%) or biliary tract (14.8%). Within the solid tumor group, no differences in cytokine levels according to entity, sex or age were observed (p>0.05). Compared to paramalignant or benign ascites, malignant ascites showed increased levels of IL-6 (2399 pg/mL vs. 963 pg/mL, p=0.002 and 560 pg/mL, p=0.003), IL-8 (200 pg/mL vs. 86 pg/mL, p=0.016 and 75 pg/mL, p=0.005), VEGF (232 pg/mL vs. 51 pg/mL, p=0.019 and 29 pg/mL, p<0.001) and sPDL1 (193 pg/mL vs. 121 pg/mL, p=0.038 and 144 pg/mL, p<0.001), respectively. No differences in cytokine levels between benign or paramalignant ascites were observed (p>0.05). Cytokines were markedly elevated in ascites compared to serum in cytokines without correlations of local and systemic levels (median ascitic IL-6 1631.5 pg/mL vs serum 25.7 pg/mL, p=0.015). For single cytokines such as IL-8 (Ï�=0.65, p=0.0013), IL-17 (Ï�=0.82, p<0.001) and C-reactive protein (Ï�=0.85, p<0.001) correlations between ascites and serum levels were observed. Additionally, survival was shorter in patients with high TNF-α levels in ascites (p=0.03).ConclusionsThese data indicate distinct inflammatory patterns of ascites in patients with solid tumors, depending on the local presence of tumor cells but independent of clinical characteristics. As TNF-α levels correlated with survival, further investigation of inflammation as a therapeutic target is warranted.Legal entity responsible for the studyThe authors.FundingThe financial support by the Austrian Federal Ministry for Digital and Economic Affairs, the National Foundation for Research, Technology and Development and the Christian Doppler Research Association is gratefully acknowledged.DisclosureT. Reiberger: Financial Interests, Institutional, Research Grant: AbbVie, Boehringer Ingelheim, Gilead, Intercept/Advanz Pharma, MSD, Myr Pharmaceuticals, Philips Healthcare, Pliant, Siemens and W. L. Gore & Associates; Financial Interests, Personal, Invited Speaker: AbbVie, Gilead, Intercept/Advanz Pharma, Roche, MSD, W. L. Gore & Associates; Financial Interests, Personal, Advisory Board: AbbVie, Astra Zeneca, Bayer, Boehringer Ingelheim, Gilead, Intercept/Advanz Pharma, MSD, Resolution Therapeutics, Siemens; Financial Interests, Personal, Other, Travel support: AbbVie, Boehringer Ingelheim, Dr. Falk Pharma, Gilead and Roche. M. Preusser: Financial Interests, Personal, Advisory Board: Bayer, Bristol Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GSK, Mundipharma, Roche, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Servier. A.S. Berghoff: Financial Interests, Institutional, Research Funding: Daiichi Sankyo (≤ 10000€), Roche (> 10000€) ; Financial Interests, Personal, Speaker, Consultant, Advisor: Roche Bristol Myers Squibb, Merck, Daiichi Sankyo (all < 5000€); Financial Interests, Personal, Other: Roche, Amgen and AbbVie. All other authors have declared no conflicts of interest.