Impact of Ghrelin-Depleting Gastrectomy on Long-Term Endocrine and Metabolic Health With a Focus on Skeletal Muscle and Bone Mineral Content.

[BACKGROUND] Advances in diagnostic and surgical techniques have improved survival rates for gastric cancer patients. However, gastrectomy involving ghrelin-secreting regions of the upper gastric greater curvature can lead to long-term endocrine and metabolic disturbances, including reductions in serum ghrelin and insulin-like growth factor-1 (IGF-1), potentially contributing to skeletal muscle and bone mineral loss.

[METHODS] This prospective observational study included 35 gastric cancer patients who underwent gastrectomy between 2016 and 2018, with follow-up for 3-5 years. Patients were categorized into ghrelin-depleted (total or proximal gastrectomy) and ghrelin-preserved (distal gastrectomy) groups. Serum desacyl-ghrelin, IGF-1, and insulin-like growth factor-binding protein-3 (IGFBP-3) levels were measured, and skeletal muscle mass and bone mineral content were assessed.

[RESULTS] The ghrelin-depleted group exhibited significantly lower serum desacyl-ghrelin (56.9 ± 27.9 vs. 111.2 ± 54.8 fmol/mL,  = 0.0006), skeletal muscle mass (87.7% ± 2.1% vs. 95.1% ± 2.4%,  = 0.0229), and bone mineral content (90.9% ± 13.0% vs. 99.5% ± 6.3%,  = 0.0249). Additionally, IGF-1 levels showed a significant positive correlation with skeletal muscle mass ( = 0.53,  = 0.020). While the correlation between IGF-1 and bone mineral content did not reach statistical significance, a positive trend was observed ( = 0.44,  = 0.062).

[CONCLUSION] Gastrectomy involving resection of ghrelin-rich regions leads to long-term reductions in serum desacyl-ghrelin levels, adversely affecting skeletal muscle mass and bone mineral content. These findings highlight the importance of considering the endocrine consequences when selecting surgical procedures.