Per- and polyfluoroalkyl substances (PFAS) exposure in melanoma patients: a retrospective study on prognosis and histological features.

Per- and polyfluoroalkyl substances (PFAS) are endocrine disrupting chemicals which could be associated with cancer development, such as kidney and testicular cancers, pancreatic and hepatocellular carcinoma and thyroid tumor. Available scientific literature offers no information on the role of PFAS in melanoma development/progression. Since 1965, a massive environmental contamination by PFAS has occurred in northeastern Italy. This study compared histopathology and prognosis between melanoma patients exposed (n = 194) and unexposed (n = 488) to PFAS. All patients were diagnosed and/or treated for melanoma at the Veneto Oncological Institute and the University Hospital of Padua (Italy) in 1998-2014. Patients were categorized in exposed or unexposed groups according to their home address and the geographical classification of municipalities affected by PFAS contamination as provided by Veneto Government in 2018. Presence of mitoses was found in 70.5% of exposed patients and 58.7% of unexposed patients (p = 0.005). Median follow-up was 90 months (IQR 59-136). 5-year overall survival was 83.7% in exposed patients and 88.0% in unexposed patients (p = 0.20); 5-year disease-specific survival was 88.0% in exposed patients and 90.9% in unexposed patients (p = 0.50); 5-year disease-free survival was 83.8% in exposed patients and 87.3% in unexposed patients (p = 0.20). Adjusting for imbalanced characteristics at baseline (presence of mitoses), survival was not statistically different between exposed and unexposed patients (overall survival: HR 1.10, 95% CI 0.77 to 1.58, p = 0.57; disease-specific survival: HR 0.99, 95% CI 0.62 to 1.59, p = 0.99; disease-free survival: HR 1.10, 95% CI 0.74 to 1.64, p = 0.62). Although the magnitude of PFAS exposure was not quantifiable, our findings suggested that exposure to PFAS was associated with higher level of mitosis in melanoma patients, but this did not translate into a survival difference. Further studies are required to investigate this relationship and all effects of PFAS on prognosis.

Metabolic syndrome, non-alcoholic fatty liver disease and liver stiffness in psoriatic arthritis and psoriasis patients.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD), potentially evolving into liver fibrosis (LF), is frequent in psoriasis (PsO), but data in psoriatic arthritis (PsA) are lacking. Our study aimed to investigate the prevalence of NALFD and LF in PsA/PsO and the contribution of arthritis in their onset. METHOD: PsA and PsO patients were consecutively enrolled. Exclusion criteria were liver diseases causing fibrosis (except NAFLD), alcohol ≥ 20 g/day, daily use of non-steroidal anti-inflammatory drugs and current/previous methotrexate use. Clinical history, biochemical and clinimetrical data and insulin-resistance index HOMA (homeostatic model assessment) were assessed. Patients underwent a liver ultrasound to identify steatosis (therefore NAFLD) and transient elastography, to evaluate LF (stiffness≥ 7 kPa = fibrosis). Statistical analysis included basic statistics, logistic and linear regression analyses (to assess the contribution of arthritis to NAFLD and LF grading, respectively) and Spearman's correlations; p ≤ 0.05 was considered significant. RESULTS: Seventy-six patients were enrolled (PsA/PsO 43/33). MetS and LF prevalence were similar between PsA and PsO (35% vs 33%, p = 0.88; 31% vs 28%, p = 0.77, respectively). NAFLD was more frequent in PsO (65% vs 35%, p = 0.044). In multivariable models with NAFLD and LF grading as outcomes, arthritis was not a significant predictor, while HOMA was independently associated with both (OR 1.34; 95%CI 1.06, 1.69; beta 0.88; 95%CI 0.54, 1.21, respectively). Female sex was independently associated with LF grading (beta 1.81; 95%CI 0.05, 3.57). CONCLUSIONS: NAFLD was more frequent in PsO, but MetS and LF prevalence were similar in PsA and PsO. Insulin resistance is the main determinant of NAFLD and LF, while additional contribution of arthritis seems small. Key Points • The prevalence of metabolic comorbidities, including liver fibrosis, is overall quite similar between psoriatic arthritis and psoriasis. • NAFLD is more frequently found in psoriasis than psoriatic arthritis. • The contribution of arthritis in the onset of metabolic comorbidities seems small.