ABSTRACT
Endothelial dysfunction plays a key role in the development of liver cirrhosis. Among the biomarkers of endothelial dysfunction, the soluble form of Vascular Adhesion Protein-1 (sVAP-1) is an unconventional and less known adhesion molecule endowed also with amine oxidase activity. The aim of this study was to explore and correlate the behavior of sVAP-1 with that of the soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) and with the severity of liver cirrhosis. A cross-sectional study was carried out by enrolling 28 controls, 59 cirrhotic patients without hepatocellular carcinoma, and 56 patients with hepatocellular carcinoma (HCC), mainly caused by alcohol abuse. The levels of adhesion molecules and of the pro-inflammatory cytokines (IL-6 and TNF-αα) were determined by immunoassay and the enzymatic activity of sVAP-1 by a fluorometric assay. In non-diabetic patients without HCC, a specific behavior of sVAP-1 was highlighted. Differently from sVCAM-1, sICAM-1, and cytokines, the sVAP-1 level was significantly increased only in the early stage of disease, and then, it decreased in the last stage (866 ± 390 ng/mL vs. 545 ± 316 ng/mL, in Child-Pugh class A vs. C, respectively, p < 0.05). Bivariate analysis correlates sVAP-1 to sVCAM-1, in the absence of HCC (Spearman's rho = 0.403, p < 0.01). Multiple linear regression analysis revealed that sVCAM-1 appears to be a predictor of sVAP-1 (ß coefficient = 0.374, p = 0.021). In conclusion, in non-diabetic and non-HCC cirrhotic patients, sVAP-1 may be a potential prognostic biomarker that, together with sVCAM-1 and pro-inflammatory cytokines, may provide information on the progression of sinusoidal liver endothelium damage.
Subject(s)
Amine Oxidase (Copper-Containing) , Biomarkers , Carcinoma, Hepatocellular , Liver Cirrhosis , Vascular Cell Adhesion Molecule-1 , Humans , Male , Liver Cirrhosis/blood , Liver Cirrhosis/diagnosis , Female , Middle Aged , Biomarkers/blood , Vascular Cell Adhesion Molecule-1/blood , Prognosis , Carcinoma, Hepatocellular/blood , Aged , Amine Oxidase (Copper-Containing)/blood , Liver Neoplasms/blood , Cross-Sectional Studies , Intercellular Adhesion Molecule-1/blood , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Adult , Tumor Necrosis Factor-alpha/blood , Cytokines/blood , Cell Adhesion MoleculesABSTRACT
BACKGROUND: Screening significantly reduces mortality from colorectal cancer (CRC). Screen detected (SD) tumors associate with better prognosis, even at later stage, compared to non-screen detected (NSD) tumors. We aimed to evaluate the association between diagnostic modality (SD vs. NSD) and short- and long-term outcomes of patients undergoing surgery for CRC. MATERIALS AND METHODS: This retrospective cohort study involved patients aged 50-69 years, residing in Veneto, Italy, who underwent curative-intent surgery for CRC between 2006 and 2018. The clinical multi-institutional dataset was linked with the screening dataset in order to define diagnostic modality (SD vs. NSD). Short- and long-term outcomes were compared between the two groups. RESULTS: Of 1,360 patients included, 464 were SD (34.1%) and 896 NSD (65.9%). Patients with a SD CRC were more likely to have less comorbidities (p = 0.013), lower ASA score (p = 0.001), tumors located in the proximal colon (p = 0.0018) and earlier stage at diagnosis (p < 0.0001). NSD patients were found to have more aggressive disease at diagnosis, higher complication rate and higher readmission rate due to surgical complications (all p < 0.05). NSD patients had a significantly lower Disease Free Survival and Overall Survival (all p < 0.0001), even after adjusting by demographic, clinic-pathological, tumor, and treatment characteristics. CONCLUSIONS: SD tumors were associated with better long-term outcomes, even after multiple adjustments. Our results confirm the advantages for the target population to participate in the screening programs and comply with their therapeutic pathways.
