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Gastric development of pancreatic acinar cell metaplasia after Vonoprazan therapy in rats

  • 2023 SAGES Oral
  • Published:
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Abstract

Background

Vonoprazan is a new acid-suppressing drug that received FDA approval in 2022. It reversibly inhibits gastric acid secretion by competing with the potassium ions on the luminal surface of the parietal cells (potassium-competitive acid blockers or P-CABs). Vonoprazan has been on the market for a short time and there are many clinical trials to support its clinical application. However, medical experience and comprehensive clinical data is still limited, especially on how and if, gastric histology is altered due to therapy.

Methods

A 12-week experiment trial with 30 Wistar rats was to assess the presence of gastrointestinal morphologic abnormalities upon administration of omeprazole and vonoprazan. At six weeks of age, rats were randomly assigned to one of 5 groups: (1) saline as negative control group, (2) oral omeprazole (40 mg/kg), as positive control group, (3) oral omeprazole (40 mg/kg) for 4 weeks, proceeded by 8 weeks off omeprazole, (4) oral vonoprazan (4 mg/kg), as positive control group, and (5) oral vonoprazan (4 mg/kg) for 4 weeks, proceeded by 8 weeks off vonoprazan.

Results

We identified non-inflammatory alterations characterized by parietal (oxyntic) cell loss and chief (zymogen) cell hyperplasia and replacement by pancreatic acinar cell metaplasia (PACM). No significant abnormalities were identified in any other tissues in the hepatobiliary and gastrointestinal tracts.

Conclusion

PACM has been reported in gastric mucosa, at the esophagogastric junction, at the distal esophagus, and in Barrett esophagus. However, the pathogenesis of this entity is still unclear. Whereas some authors have suggested that PACM is an acquired process others have raised the possibility of PACM being congenital in nature. Our results suggest that the duration of vonoprazan administration at a dose of 4 mg/kg plays an important role in the development of PACM.

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Acknowledgements

Dr. Rodrigo Edelmuth was awarded with the 2022 Career Development Award, provided by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES).

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Authors and Affiliations

  1. Department of Surgery, Division of Endocrine & Minimally Invasive Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, 525 East 68Th Street, K-836, New York, NY, 10065, USA

    Rodrigo C. L. Edelmuth, Maria Cristina Riascos, Hala Al Asadi, Jacques A. Greenberg, Haythem Najah, Brendan M. Finnerty, Thomas J. Fahey & Rasa Zarnegar

  2. Laboratory of Comparative Pathology, Weill Cornell Medical College, New York-Presbyterian Hospital, Memorial Sloan Kettering Cancer Center, The Rockefeller University, New York, NY, USA

    Ileana C. Miranda

  3. Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA

    Carl V. Crawford & Felice H. Schnoll-Sussman

  4. Hospital Israelita Albert Einstein, São Paulo, Brazil

    Rodrigo C. L. Edelmuth

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  1. Rodrigo C. L. Edelmuth
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Correspondence to Rasa Zarnegar.

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Disclosures

Dr. Rasa Zarnegar works as a consultant for Bard (BD). Dr. Philip Katz works as a consultant for Phathom Pharma. Rodrigo C.L. Edelmuth, Maria Cristina Riascos, Hala Al Asad, Haythem Najah, Jacques A. Greenberg, Ileana C. Miranda, Carl V. Crawford, Felice H Schnoll-Sussman, Philip O. Katz, Brendan M. Finnerty, Thomas J. Fahey III have no conflicts of interest or financial ties to disclose. The Laboratory of Comparative Pathology is supported the NCI Cancer Center Support Grant P30 CA008748.

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Edelmuth, R.C.L., Riascos, M.C., Al Asadi, H. et al. Gastric development of pancreatic acinar cell metaplasia after Vonoprazan therapy in rats. Surg Endosc 37, 9366–9372 (2023). https://doi.org/10.1007/s00464-023-10371-9

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