Obesity
Conditions
Keywords
gastric carcinogenesis, immunopathological changes, gastric mucosa
Brief summary
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.
Detailed description
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.
Interventions
PROCEDUREbariatric surgery laparoscopic sleeve gastrectomy
Adipose tissue macrophages (ATMs), mast cells positive for tryptase (MCPT), and microvascular density (MVD) were assessed by immunohistochemistry. Quantitative assessment was performed using a light microscope. For each GTO and NT tissue section, five highly immunostained areas ("hot spots") were identified at low magnification.
PROCEDURElean control patients undergoing endoscopic biopsy for benign or malignant gastric conditions.
Adipose tissue macrophages (ATMs), mast cells positive for tryptase (MCPT), and microvascular density (MVD) were assessed by immunohistochemistry. Quantitative assessment was performed using a light microscope. For each GTO and NT tissue section, five highly immunostained areas ("hot spots") were identified at low magnification.
Sponsors
General Committee of Teaching Hospitals and Institutes, Egypt
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunohistochemistry | Baseline | Compare the 2 groups: Adipose tissue macrophages (ATMs) was assessed by immunohistochemistry using a three-step biotin-avidin-peroxidase detection method. five-micrometer-thick serial sections were cut from formalin-fixed, paraffin-embedded gastric tissue of obese (GTO) and control normal tissue (NT) samples. Antigen retrieval was performed using a microwave oven (500 W for 10 minutes), followed by endogenous peroxidase blocking with a 3% hydrogen peroxide solution. Slides were incubated with the following primary antibodies for 1 hour at room temperature: * Anti-tryptase (clone AA1; Dako, Glostrup, Denmark; 1:100) for mast cell identification, * Anti-CD68 (clone KP1; Dako, Glostrup, Denmark; 1:100) for ATM detection, * Anti-CD31 (clone QB-END 10; Bio-Optica, Milan, Italy; 1:50) as a pan-endothelial marker to assess MVD. |
| Morphometric Analysis | Baseline | Compare the 2 groups: Quantitative assessment was performed using a light microscope. For GTO tissue section, five highly immunostained areas ("hot spots") were identified at low magnification. ATMs, MCPT, and MVD were then quantified at ×40 magnification. The mean value across five hot spots per marker was used for each sample. To evaluate mast cell degranulation, the presence of tryptase-positive granules in the extracellular matrix was examined. Degranulating mast cells were identified by the diffusion of immunoreactive granules outside the cell boundaries, indicating active release of tryptase. This extracellular localization of tryptase provided morphological evidence of mast cell activation and was considered a marker of tissue inflammation and remodeling. |
| Morphometric analysis | Baseline | Compare the 2 groups: Quantitative assessment was performed using a light microscope. For NT tissue section, five highly immunostained areas ("hot spots") were identified at low magnification. ATMs, MCPT, and MVD were then quantified at ×40 magnification. The mean value across five hot spots per marker was used for each sample. To evaluate mast cell degranulation, the presence of tryptase-positive granules in the extracellular matrix was examined. Degranulating mast cells were identified by the diffusion of immunoreactive granules outside the cell boundaries, indicating active release of tryptase. This extracellular localization of tryptase provided morphological evidence of mast cell activation and was considered a marker of tissue inflammation and remodeling. |
Countries
Egypt
Outcome results
None listed