Survival and chance of reversal after intestinal stoma formation during cytoreductive surgery for advanced ovarian cancer; a population-based cohort study.

OBJECTIVE: Our objective was to examine oncologic outcome in women with advanced epithelial ovarian cancer (aEOC) receiving an intestinal stoma (IS) at the time of cytoreductive surgery (CRS), probability of stoma reversal (SR) and variables affecting odds of SR. METHODS: This population-based cohort study included all women diagnosed with aEOC between 2009 and 2018 in the Stockholm/Gotland Region of Sweden. The association between IS formation at CRS and survival was analyzed with proportional hazards regression yielding hazard ratios (HR) with 95% confidence intervals (CI), adjusted for predefined confounders. Cumulative incidence functions, with death or recurrence as competing risk, were used to estimate chance of SR. The association between clinical factors and SR was analyzed with logistic regression yielding odds ratios (OR) with 95% CI. RESULTS: The final analysis included 888 women undergoing CRS for aEOC. Of these, 129 (14,5%) received an IS of which 74% (n = 95) were defunctioning and 26% (n = 34) permanent. IS was associated with an increased hazard of death (HR 1.30, CI 95%, 1.05-1.61; p = 0.02) in the univariate analysis, however not in the adjusted analysis. The probability of SR of defunctioning IS within 2 years was 48% (95% CI, 38-58). Median time to SR was 10 months. High surgical complexity score (SCS) was associated with increased odds of reversal (OR 3.43, 95% CI, 1.06-11.05; p = 0.04). CONCLUSIONS: IS formation does not seem to affect prognosis in women with aEOC. We could not identify any factor, known at time of CRS, that may predict the odds of SR except a high SCS.

Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion.

Extracellular vesicles (EVs), comprising exosomes, microvesicles, and apoptotic bodies, are released by all cells into the extracellular matrix and body fluids, where they play important roles in intercellular communication and matrix remodeling in various pathological conditions. Malignant pleural mesothelioma (MPM) is a primary tumor of mesothelial origin, predominantly related to asbestos exposure. The detection of MPM at an early stage and distinguishing it from benign conditions and metastatic adenocarcinomas (AD) is sometimes challenging. Pleural effusion is often the first available biological material and an ideal source for characterizing diagnostic and prognostic factors. Specific proteins have previously been identified as diagnostic markers in effusion, but it is not currently known whether these are associated with vesicles or released in soluble form. Here, we study and characterize tumor heterogeneity and extracellular vesicle diversity in pleural effusion as diagnostic or prognostic markers for MPM. We analyzed extracellular vesicles and soluble proteins from 27 pleural effusions, which were collected and processed at the department of pathology and cytology at Karolinska University Hospital, representing three different patient groups, MPM (n = 9), benign (n = 6), and AD (n = 12). The vesicles were fractionated into apoptotic bodies, microvesicles, and exosomes by differential centrifugation and characterized by nanoparticle tracking analysis and Western blotting. Multiplex bead-based flow cytometry analysis showed that exosomal markers were expressed differently on EVs present in different fractions. Further characterization of exosomes by a multiplex immunoassay (Luminex) showed that all soluble proteins studied were also present in exosomes, though the ratio of protein concentration present in supernatant versus exosomes varied. The proportion of Angiopoietin-1 present in exosomes was generally higher in benign compared to malignant samples. The corresponding ratios of Mesothelin, Galectin-1, Osteopontin, and VEGF were higher in MPM effusions compared to those in the benign group. These findings demonstrate that relevant diagnostic markers can be recovered from exosomes.