Gastric neuroendocrine tumors arising from chronic proton pump inhibitor use: characteristics and outcomes of a fourth subtype

Abstract

Background: Gastric neuroendocrine tumors (NETs) are categorized into 3 types. Types I and II are indolent and are associated with hypergastrinemia. In contrast, Type III is sporadic and more aggressive and typically requires gastrectomy and lymphadenectomy. Widespread proton pump inhibitor (PPI) use, which induces hypergastrinemia, has led to the proposal of a distinct fourth subtype. This study aimed to characterize this potential PPI-related Type IV gastric NET.

Methods: A retrospective review was conducted of patients diagnosed as having gastric NETs from 2012 to 2022 at a single institution. Types I and II tumors were excluded. Patients with ≥1 year of PPI use were classified as having Type IV tumors, and the remainder were classified as having Type III. Clinical variables were compared using chi-square, Fisher's exact, or Mann-Whitney U test. Kaplan-Meier analysis with log-rank testing was used for time-to-event outcomes.

Results: A total of 79 patients met the inclusion criteria: 34 (43.0%) with Type III and 45 (57.0%) with Type IV gastric NETs. Compared with Type III, Type IV tumors were significantly less likely to involve lymph nodes (0% vs 23.5%; P <.01) or present with distant metastases (4.4% vs 26.5%; P <.01). Recurrence patterns also differed: Type IV tumors exhibited only local recurrences, whereas Type III tumors had exclusively distant recurrences (P =.03). Type IV NETs demonstrated superior cancer-specific (P =.007) and progression-free survival (P =.037).

Conclusion: Type IV gastric NETs in long-term PPI users seem to represent a distinct, indolent subtype. Their favorable outcomes may allow for nonsurgical management, although ongoing endoscopic surveillance and PPI discontinuation are critical owing to the frequent local recurrence.

Keywords: Gastrointestinal neoplasms; Neuroendocrine tumors; Proton pump inhibitor.