Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Developing biomarkers for early detection and chemotherapeutic response prediction is crucial to improve the dismal prognosis of PDAC patients. However, molecular cancer signatures based on transcriptome analysis do not reflect intratumoral heterogeneity. To explore a more accurate stratification of PDAC phenotypes in an easily accessible matrix, plasma metabolome analysis using MxP^® Global Profiling and MxP^® Lipidomics was performed in 361 PDAC patients. We identified three metabolic PDAC subtypes associated with distinct complex lipid patterns. Subtype 1 was associated with reduced ceramide levels and a strong enrichment of triacylglycerols. Subtype 2 demonstrated increased abundance of ceramides, sphingomyelin and other complex sphingolipids, whereas subtype 3 showed decreased levels of sphingolipid metabolites in plasma. Pathway enrichment analysis revealed that sphingolipid-related pathways differ most among subtypes. Weighted correlation network analysis (WGCNA) implied PDAC subtypes differed in their metabolic programs. Interestingly, a reduced expression among related pathway genes in tumor tissue was associated with the lowest survival rate. However, our metabolic PDAC subtypes did not show any correlation to the described molecular PDAC subtypes. Our findings pave the way for further studies investigating sphingolipids metabolisms in PDAC.

Background: Early-onset colorectal cancer (eoCRC), defined as a colorectal cancer (CRC) in patients younger than 50 years old, shows an increasing incidence worldwide in the latest years. The role of exogenous factors associated with CRC has been largely overlooked in eoCRC. Here, we conducted a case-control study to evaluate the diet and the lifestyle habits in an Italian population of patients with eoCRC, compared to age-matched healthy controls (HCs). Methods: We enrolled 118 subjects (47 cases, 71 controls) in a third-level academic hospital. We analyzed epidemiological features (age, sex, body mass index), lifestyle behaviors (smoking habits, physical activity, type of diet, use of dietary supplements), and eating habits (semiquantitative food-frequency questionnaire) in eoCRCs and HCs, covering the previous 5 years. Results: In our cohort, positive family history of CRC was significantly associated with the development of eoCRC (p = 0.004). Fresh meat (p = 0.003), processed meat (p < 0.001), dairy products (p = 0.013), and smoking (p = 0.0001) were significantly associated with eoCRC compared to controls. Other variables did not differ significantly between the two groups. Conclusion: Fresh and processed meat, dairy products, and smoking could be considered significant risk factors for eoCRC, although further confirmation by international multicenter studies is desirable. Diet and smoking could be the main areas of future interventions for eoCRC primary prevention.

Aims: The acute respiratory distress syndrome (ARDS) is a frequent condition following pneumonia in immunocompromised cancer patients. Extracorporeal membrane oxygenation (ECMO) may serve as a rescue therapy in refractory ARDS but has still not been studied in predominantly leuco- and thrombocytopenic cancer patients. Patients and Methods: In this monocentric, retrospective, observational study, we assessed all cancer patients treated with ECMO for ARDS between 2013 and 2017. Results: 25 patients, 11 of whom underwent haematopoietic stem cell transplantation (SCT), were analysed. The main reason for ARDS was pneumonia in 72%. All patients were under invasive ventilation at ECMO. All but 9/3 patients suffered from leuco-/thrombocytopenia due to anti-cancer treatment or underlying disease. Overall, 17 patients (68%) died on ECMO, whereas 5 patients survived to hospital discharge (20%). All patients after recent allogeneic (allo-)SCT have died. 4 patients experienced severe bleeding events. Conclusions: Discouraging survival rates in patients treated after allo-SCT do not support the use of ECMO for ARDS in this patient subgroup. On the contrary, cancer patients in at least stable disease otherwise eligible for full-code intensive care unit management, even those with severe thrombocytopenia, may be potential candidates for ECMO in case of severe ARDS failing conventional measures.