The gut microbiota significantly impacts the development and progression of upper gastrointestinal (GI) cancers, including esophageal and gastric cancers. Microbial dysbiosis contributes to carcinogenesis through mechanisms such as inflammation, immune modulation, and direct DNA damage. Techniques for sampling oral, esophageal, and gastric microbiota vary, with standardization being essential for reliable results. Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) are associated with an enrichment of Gram-negative bacteria, promoting inflammation and cancer progression. Esophageal squamous cell carcinoma (ESCC) also shows distinct microbial patterns, with reduced diversity and increased harmful bacteria like Porphyromonas gingivalis and Fusobacterium nucleatum. In gastric cancer (GC), Helicobacter pylori (HP) and non-HP gastric microbiota play significant roles, with diverse microbial communities contributing to cancer development through nitrate reduction, immune modulation, and inflammation. Emerging evidence highlights the role of non-HP bacteria in promoting carcinogenesis, with specific taxa like Fusobacterium nucleatum and Lactobacillus influencing tumor growth and immune evasion. Further research is needed to elucidate the complex interactions between gut microbiota and upper GI cancers, paving the way for novel diagnostic and therapeutic approaches. Understanding these microbial dynamics offers potential for microbiota-based interventions, improving the early detection, prognosis, and treatment of upper GI cancers. This comprehensive review summarizes the available evidence on the role of microbiota in upper GI oncology and the need for continued exploration in this field.

Background/Objectives: Large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs) are challenging lesions with a variable, yet non-negligible risk of advanced neoplasia. While correct management is therefore mandatory, a discrepancy often persists between guideline recommendations and daily endoscopic practice. To bridge this gap, we performed a comprehensive and structured review of the available evidence, aiming to synthesize the current knowledge and provide practice-oriented guidance for the optimal management of LNPCPs throughout the diagnostic–therapeutic pathway. Methods: A comprehensive literature review was independently performed. We systematically searched PubMed and Google Scholar up to December 2025. After the literature review, we identified the most clinically relevant and controversial aspects in the endoscopic management of LNPCPs. These key areas were then translated into focused, practice-oriented clinical questions. Results: We formulated 14 practice-oriented questions addressing the key steps of endoscopic management of LNPCPs. These questions cover the entire diagnostic–therapeutic pathway, including lesion detection, morphological characterization, optical diagnosis and risk stratification for submucosal invasion, selection of the optimal resection technique, and post-resection surveillance strategies. For each question, the current evidence was synthesized to provide concise, clinically applicable answers aimed at supporting real-world endoscopic decision-making. Conclusions: The endoscopic management of LNPCPs requires a structured and evidence-based approach that integrates accurate assessment, appropriate technique selection, and tailored post-resection surveillance. By framing current evidence into focused, practice-oriented questions, this review aims to bridge the gap between guideline recommendations and real-world endoscopic practice. The proposed framework may support endoscopists in daily clinical decision-making, promoting the appropriate use of advanced endoscopic techniques and ultimately improving patient outcomes.

Background/Objectives: Gastric precancerous conditions and early gastric cancer represent a heterogeneous disease spectrum with variable malignant potential and complex management pathways. Despite well-established international guidelines, discrepancies remain between recommended strategies and routine clinical practice, particularly regarding endoscopic diagnosis, risk stratification, therapeutic selection, and follow-up. This review aims to synthesize current evidence and provide practice-oriented, question-based guidance for the management of gastric precancerous lesions and early gastric cancer. Methods: A comprehensive review of the literature was conducted using PubMed and Google Scholar, focusing on endoscopic diagnosis, histological risk assessment, therapeutic options, and surveillance strategies for gastric precancerous lesions and early gastric cancer. Key areas of clinical uncertainty and controversy were identified and translated into focused, practice-oriented clinical questions designed to reflect and possibly help to improve real-world gastroenterological practice. Results: Clinical questions were formulated to cover the entire management pathway, from endoscopic detection and characterization to therapeutic decision-making and post-treatment surveillance. Topics include high-quality endoscopic diagnosis, biopsy strategies, histological staging system, selection between endoscopic and surgical therapy, and follow-up according to individual risk profile. For each question, current evidence is summarized into concise, actionable recommendations. Conclusions: Management of gastric precancerous lesions and early gastric cancer requires a structured and individualized approach, integrating high-quality endoscopy, accurate histological risk stratification, and evidence-based therapeutic and surveillance strategies. Organizing available evidence into practice-oriented clinical questions may help harmonize clinical practice, reduce unwarranted variability, and support gastroenterologists in delivering optimal patient-centered care.

Background/Objectives: Gastric precancerous conditions and early gastric cancer rep-resent a heterogeneous disease spectrum with variable malignant potential and complex management pathways. Despite well-established international guidelines, discrepancies remain between recommended strategies and routine clinical practice, particularly regarding endoscopic diagnosis, risk stratification, therapeutic selection, and follow-up. This review aims to synthesize current evidence and provide practice-oriented, question-based guidance for the management of gastric precancerous lesions and early gastric cancer. Methods: A comprehensive review of the literature was conducted using PubMed and Google Scholar, focusing on endoscopic diagnosis, histological risk assessment, thera-peutic options, and surveillance strategies for gastric precancerous lesions and early gastric cancer. Key areas of clinical uncertainty and controversy were identified and translated into focused, practice-oriented clinical questions designed to reflect and possibly help to improve real-world gastroenterological practice. Results: Clinical questions were formulated to cover the entire management pathway, from endoscopic detection and characterization to therapeutic decision-making and post-treatment surveillance. Topics include high-quality endoscopic diagnosis, biopsy strategies, histological staging system, selection between endoscopic and surgical therapy, and follow-up according to individual risk profile. For each question, current evidence is summarized into concise, actionable recommendations. Conclusions: Management of gastric precancerous lesions and early gastric cancer requires a structured and individualized approach integrating high-quality endoscopy, accurate histological risk stratification, and evidence-based therapeutic and surveillance strategies. Organizing available evidence into practice-oriented clinical questions may help harmonize clinical practice, reduce unwarranted variability, and support gastroenterologists in delivering optimal patient-centered care.