The scientific data to guide the management of Peutz–Jeghers syndrome (PJS) are sparse. The available evidence has been reviewed and discussed by diverse medical specialists in the field of PJS to update the previous guideline from 2010 and formulate a revised practical guideline for colleagues managing PJS patients. Methods: Literature searches were performed using MEDLINE, Embase, and Cochrane. Evidence levels and recommendation strengths were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). A Delphi process was followed, with consensus being reached when ≥80% of the voting guideline committee members agreed. Recommendations and statements: The only recent guidelines available were for gastrointestinal and pancreatic management. These were reviewed and endorsed after confirming that no more recent relevant papers had been published. Literature searches were performed for additional questions and yielded a variable number of relevant papers depending on the subject addressed. Additional recommendations and statements were formulated. Conclusions: A decade on, the evidence base for recommendations remains poor, and collaborative studies are required to provide better data about this rare condition. Within these restrictions, multisystem, clinical management recommendations for PJS have been formulated.

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The incidence of early-onset colorectal cancer, defined as colorectal cancer occurring in young adults under the age of 50, is increasing globally. Knowledge of the etiological factors in young adults is far from complete. Questionable eoCRCs’ exogenous factors are represented by processed meat, sugary drinks, alcohol, Western dietary pattern, overweight and obesity, physical inactivity, and smoking, though with heterogeneous results. Therefore, we performed a systematic review to summarize the current evidence on the role of diet and lifestyle as eoCRC risk factors. We systematically searched PubMed, Scopus, and EMBASE up to July 2021, for original studies evaluating diet, alcohol, physical activity, BMI, and smoking in eoCRC and included twenty-six studies. Indeed, the exogenous factors could represent modifiable key factors, whose recognition could establish areas of future interventions through public health strategies for eoCRC primary prevention. Additionally, we discussed the role of additional non-modifiable risk factors, and of epigenetic regulation and microbiota as mediators of the eoCRC triggered by diet and lifestyle.