Obesity is a global health problem that has reached epidemic proportions, affecting more than one billion people worldwide and significantly increasing the risk of multiple comorbidities, including type 2 diabetes, cardiovascular diseases, and cancer (World Health Organization, 2024). Increasing evidence suggests that chronic low-grade inflammation associated with obesity plays a critical role in the development of obesity-related malignancies, including gastric cancer. Adipose tissue dysfunction in obesity leads to the recruitment and activation of various immune cells, such as macrophages and mast cells, which contribute to a pro-inflammatory microenvironment through the release of cytokines, growth factors, and angiogenic mediators.

In the gastric mucosa, this inflammatory micro environment associated with obesity may promote epithelial proliferation, DNA damage, and neovascularization, establishing conditions favorable for early carcinogenic transformation. Mast cells presence at the periphery and infiltrating tumors, argues for their role in the modulation of tumor biology it has been implicated in tumor progression through their ability to release histamine, tryptase, and vascular endothelial growth factor (VEGF), thereby enhancing angiogenesis and stromal remodeling. Similarly, macrophages especially those exhibiting an M2-like phenotype can facilitate tissue remodeling and angiogenesis, further supporting tumor initiation. The number and phenotype of macrophages vary at different stages of tumor progression. The number of macrophages markedly increases during the early stages of tumor growth.

Despite the growing recognition of the link between obesity, inflammation, and cancer, few studies have explored the immunopathological changes occurring in the gastric mucosa of obese patients before overt malignancy. Bariatric surgery provides a unique opportunity to study these changes in human gastric tissue. Understanding alterations in mast cell and macrophage infiltration, as well as microvessel density, may throw light on the early events leading to gastric carcinogenesis in obesity.

Inclusion Criteria:

• Adult patients undergoing bariatric surgery (laparoscopic sleeve gastrectomy).
• BMI > 35 kg/m²
• All participants underwent preoperative evaluation, including blood tests and assessment by a multidisciplinary team (nutritionist, psychiatrist, endocrinologist, radiologist, anesthesiologist, and surgeon).

Exclusion Criteria:

• Patients with secondary causes of obesity, such as Cushing's syndrome or polycystic ovary syndrome (PCOS).
• Patients with malignant gastric conditions or previous gastric surgery.
• Patients with systemic inflammatory diseases, autoimmune disorders, or chronic infections that may influence immune cell infiltration.
• Patients with incomplete clinical data or poor-quality tissue samples.
• Patients taking anti-inflammatory, immunosuppressive, or corticosteroid therapy within the last 3 months before sampling.

Fifty gastric tissue samples will be collected from patients with obesity undergoing bariatric surgery and fifty from lean control patients undergoing endoscopic biopsy for benign or malignant gastric conditions. All participants underwent preoperative evaluation including blood tests.

All patients were evaluated by a multidisciplinary team consisting of a nutritionist, psychiatrist, endocrinologist, radiologist, anesthesiologist, and surgeon. Endocrinologic assessment excluded secondary causes of obesity (e.g., Cushing's syndrome, polycystic ovary syndrome). Only patients with a body mass index (BMI) > 35 kg/m² were included. All surgical procedures were laparoscopic sleeve gastrectomies (LapSG).