Association Between Long-Term Proton Pump Inhibitor Use and Low-Risk Gastric Neuroendocrine Tumors

Area of Science:

• Gastroenterology
• Oncology
• Endocrinology

Background:

• Gastric neuroendocrine tumors (NETs) are rare, with types 1 and 2 linked to hypergastrinemia and type 3 occurring sporadically and aggressively.
• Long-term proton pump inhibitor (PPI) use causes hypergastrinemia, but PPI-associated gastric NETs are infrequently reported and lack clear classification.

Purpose of the Study:

• To investigate the characteristics and outcomes of gastric NETs in patients with a history of long-term PPI use.
• To determine if PPI use influences the aggressiveness and metastatic potential of gastric NETs.

Main Methods:

• Retrospective analysis of gastric NET cases at H. Lee Moffitt Cancer Center (January 2008 - August 2023).
• Exclusion of type 1, type 2 gastric NETs, and poorly differentiated neuroendocrine carcinomas.
• Data collection on PPI use, gastrin levels, tumor grade, and disease stage for sporadic gastric NETs.

Main Results:

• 50% of 90 eligible patients had long-term PPI use (≥5 years).
• All tumors in the study were well-differentiated (grades 1-3).
• Patients with long-term PPI use had no distant metastatic disease (0%), versus 62% in those without long-term PPI use (p < 0.0001).

Conclusions:

• Gastric NETs in patients with long-term PPI use appear less aggressive than sporadic types.
• A new classification, 'type 4' gastric NETs, is proposed for PPI-associated cases.
• This proposed type 4 gastric NET has a prognosis more akin to type 1 than type 3.