Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids—What Is the Relationship?
Abstract
1. Introduction
2. Observations in Humans
3. Evidence of Causation
4. Summary
Conflicts of Interest
Appendix A. Gastric Carcinoids Associated with the Use of PPI: Summary of Features of Reported Cases
References
- Merchant, S.H.; VanderJagt, T.; Lathorp, S.; Amin, M.B. Sporadic duodenal bulb gastrin-cell tumors: Association with Helicobacter pylori gastritis and Long-term use of proton pump inhibitors. Am. J. Surg. Pathol. 2006, 30, 1581–1587. [Google Scholar] [CrossRef] [PubMed]
- Sunderasan, S.; Meininger, C.A.; Kang, A.J.; Photenhauer, A.L.; Hayes, M.M.; Sahoo, N.; Grembecka, J.; Cierpicki, T.; Ding, T.; Giordano, T.J.; et al. Gastrin induces nuclear export and proteasome degradation of Menin in enteric glial cells. Gastroenterology 2017, 153, 1555–1567. [Google Scholar] [CrossRef] [PubMed]
- Pearse, A.G. The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J. Histochem. Cytochem. 1969, 17, 303–313. [Google Scholar] [CrossRef] [PubMed]
- Dasari, A.; Shen, C.; Halperin, D.; Zhao, B.; Zhou, S.; Xu, Y.; Shih, T.; Yao, J.C. Trends in the incidence, prevalence and survival outcomes in patients with Neuroendocrine tumors in the United States. JAMA Oncol. 2017, 3, 1335–1342. [Google Scholar] [CrossRef]
- Ellis, L.; Shale, M.J.; Coleman, M.P. Carcinoid tumors in the gastrointestinal tract: Trends in incidence in England since 1971. Am. J. Gastroenterol. 2010, 105, 2563–2569. [Google Scholar] [CrossRef]
- Modlin, I.M.; Kidd, M.; Latich, I.; Zikusoka, M.N.; Shapiro, M.D. Current status of gastrointestinak carcinoids. Gastroenterology 2005, 128, 1717–1751. [Google Scholar] [CrossRef]
- Scherubl, H.; Cadiot, G.; Jensen, R.T.; Rosch, T.; Stölzel, U.; Klöppel, G. Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: Small tumors, small problems? Endoscopy 2010, 42, 664–671. [Google Scholar] [CrossRef]
- Jensen, R.T.; Norton, J.A.; Oberg, K. Neuroendocrine Tumors. In Sleisenger and Fordtran’s Textbook of Gastroenterology and Liver Disease, 10th ed.; Feldman, L.S., Brandt, L.J., Eds.; Elsevier: Philladelphia, PA, USA, 2016; pp. 501–541. [Google Scholar]
- Rimdi, G.; Arnold, R.; Bosman, F.T.; Capella, C.; Bosman, F.T. WHO Classification of Tumours of the Digestive System; IARC Press: Lyon, France, 2010; pp. 13–14. [Google Scholar]
- Tang, L.H.; Untch, B.R.; Reidy, D.L.; O’Reilly, E. Well differentiated neuroendocrine tumors with a morphologically high grade component: A pathway distinct from poorly differentiated neuroendocrine carcinoma. Clin. Cancer Res. 2016, 22, 1011–1017. [Google Scholar] [CrossRef]
- Lee, L.; Ramos-Alvarez, I.; Ito, T.; Jensen, R.T. Insights into effects/risks of chronic hypergastrinemia and lifelong PPI treatment in man based on studies of patients with Zollinger-Ellison Syndrome. Int. J. Mol. Sci. 2019, 20, 5128. [Google Scholar] [CrossRef]
- Nandy, N.; Hanson, J.A.; Strickland, R.S.; McCarthy, D.M. Solitary gastric carcinoid associated with longterm use of omeprazole: A case report and review of the literature. Dig. Dis. Sci. 2016, 61, 708–712. [Google Scholar] [CrossRef]
- Kidd, M.; Gustafsson, B.; Modlin, I.M. Gastric Carcinoids (Neuroendocrine Neoplasms). Gastroenterol. Clin. N. Am. 2013, 42, 381–397. [Google Scholar] [CrossRef] [PubMed]
- Fossmark, R.; Sordal, O.; Jianu, C.S.; Qvigstad, G. Treatment of gastric carcinoid type-1with the gastrin receptor antagonist netazeoide (YF476) results in regression of tumors and normalization of serum chromogranin A. Aliment. Pharmacol. Ther. 2012, 36, 1067–1075. [Google Scholar] [CrossRef] [PubMed]
- McCarthy, D.M. Commentary: A gastrin antagonist against carcinoids - implications for PPI-induced hypergastrinemia. Aliment. Pharmacol. Ther. 2013, 37, 276–277. [Google Scholar] [CrossRef] [PubMed]
- Crystal, D.; Kamilaris, C.; Startakis, C.A. Multiple Endocrine Neoplasia Type 1 (MEN-1): An update and the significance of early genetic and clinical diagnosis. Front. Endocrinol. 2019, 10, 339–367. [Google Scholar] [CrossRef]
- Veniaminova, N.A.; Hayes, M.M.; Varrney, J.M.; Merchant, J.L. Conditional deletion of Menin results in antral G-cell hyperplasia and hypergastrinemia. Am. J. Physiol. Gastrointest. Liver Physiol. 2012, 303, G752–G764. [Google Scholar] [CrossRef]
- Anlauf, M.; Perren, A.; Henopp, T.; Rudolph, T. Allelic deletion of the MEN 1 gene in duodenal gastrin and somatostatin cell neoplasms and their precursor lesions. Gut 2016, 56, 637–644. [Google Scholar] [CrossRef]
- Cives, M.; Strosberg, J.R. Gastroenteropancreatic Neuroendocrine Tumors. CA A Cancer J. Clin. 2018, 68, 471–487. [Google Scholar] [CrossRef]
- Richards, M.L.; Gauger, P.; Thompson, N.W.; Giordano, T.J. Regression of type11 gastric carcinoids in Multiple Endocrine Neoplasia Type1patients with Zollinger-Ellison Syndrome after surgical excision of all gastrinomas. World J. Surg. 2004, 28, 652–658. [Google Scholar] [CrossRef]
- Kinoshita, Y.; Ishihara, S.; Kadowaki, Y.; Fukui, H. Reg Protein is a unique growth factor of gastric mucosal cells. J. Gastronterol. 2004, 39, 507–513. [Google Scholar] [CrossRef]
- Waldum, H.L.; Sordal, O.F.; Mjones, P.G. The enterochromaffin-like [ECL] cell—Central in Gastric physiology and pathology. Int. J. Mol. Sci. 2019, 20, 2444. [Google Scholar] [CrossRef]
- Fossmark, R.; Martinsen, T.C.; Waldum, H.L. Adverse effects of proton pump inhibitors—Evidence and plausibility. Int. J. Mol. Sci. 2019, 20, 5203. [Google Scholar] [CrossRef]
- Calvete, O.; Reyes, J.; Zuniga, S.; Paumard-Hernandez, B. Exome sequencing identifies ATP4A gene as responsible for an atypical familial type 1 gastric neuroendocrine tumor. Hum. Mol. Genet. 2015, 24, 2914–2922. [Google Scholar] [CrossRef] [PubMed]
- Fossmark, R.; Calvete, O.; Mjones, P.; Benitez, J.; Waldum, H.L. ECL-cell carcinoids and carcinoma in patients homozygous for an inactivating mutation in the gastric H(+) K(+) ATPASE alpha subunit. APMIS 2016, 124, 561–566. [Google Scholar] [CrossRef] [PubMed]
- Ooji, A.; Ota, M.; Katsuda, S.; Nakanishi, I. An unusual case of multiple gastric carcinoids associated with diffuse endocrine cell hyperplasia and parietal hypertrophy. Endocr. Pathol. 1995, 6, 229–237. [Google Scholar]
- Shiotani, A.; Katsumata, R.; Gouda, K.; Fukushima, S. Hypergastrinemia in long-term use of proton pump inhibitors. Digestion 2018, 97, 154–162. [Google Scholar] [CrossRef] [PubMed]
- Helgadottir, H.; Metz, D.C.; Yang, Y.X.; Rhim, A.D.; Bjornsson, E.S. The effects of long-term therapy with proton pump inhibitors on meal stimulated gastrin. Dig. Liver Dis. 2014, 46, 125–130. [Google Scholar] [CrossRef]
- Bakke, I.; Qvigstad, G.; Brenna, E.; Sandvik, A.; Waldum, H.L. Gastrin has a specific proliferative effect on the rat entrochromaffin-like cell, but not on the parietal cell: A study by elutriation centrifugation. Acta Physiol. Scand. 2000, 169, 29–37. [Google Scholar] [CrossRef]
- Brenna, E.; Waldum, H.L. Trophic Effect of gastrin on the enterochromaffin like cells of the rat stomach: Establishment of a dose response relationship. Gut 1992, 33, 1303–1306. [Google Scholar] [CrossRef]
- Lundell, L.; Vieth, M.; Gibson, F.; Nagy, P.; Kahrilas, P.J. Systematic Review: The effects of long-term proton pump inhibitor use on serum gastrin levels and gastric histology. Aliment. Pharmacol. Ther. 2015, 42, 649–663. [Google Scholar] [CrossRef]
- Gilligan, C.; Lawton, G.; Tang, L.; West, A. Gastric carcinoid tumors: The biology and therapy of an enigmatic and controversial lesion. Am. J. Gastroenterol. 1995, 90, 330–352. [Google Scholar]
- Kidd, M.; Bodei, L.; Modlin, I.M. Chromogranin A: Any relevance in neuroendocrine tumors? Curr. Opin. Endocrinol. Diabetes Obes. 2016, 23, 28–37. [Google Scholar] [CrossRef] [PubMed]
- AL-Risi, E.S.; AL-Essry, F.S.; Mula-Abed, W.S. Chromogranin A as a biomedical marker for neuroendocrine tumors: A single center experience at Royal Hospital, Oman. Oman Med. J. 2017, 32, 365–370. [Google Scholar] [CrossRef] [PubMed]
- Haga, Y.; Nakatsura, T.; Shibata, Y.; Samashima, H. Human Gastric carcinoid detected during long-term anti-ulcer therapy of H2 receptor antagonist and proton pump inhibitor. Dig Dis Sci. 1998, 43, 253. [Google Scholar] [CrossRef]
- Dawson, R.; Manson, J.M. Omeprazole in esophageal reflux disease. Lancet 2000, 356, 1770–1771. [Google Scholar] [CrossRef]
- Attila, T.; Santharam, R.J.; Blom, D.; Komorowski, R. Multifocal gastric carcinoid tumor in patient with pernicious anemia receiving Lansoprazole. Dig. Dis. Sci. 2005, 50, 509–513. [Google Scholar] [CrossRef]
- Jianu, C.S.; Lange, O.J.; Viset, T.; Qvigstad, G. Gastric neuroendocrine carcinoma after long-term use of proton pump inhibitor. Scand. J. Gastroenterol. 2012, 47, 64–67. [Google Scholar] [CrossRef]
- Jianu, C.S.; Fossmark, R.; Viset, T.; Qvigstad, G. Gastric carcinoids after long-term use of a proton pump inhibitor. Aliment. Pharmacol. Ther. 2012, 36, 644–649. [Google Scholar] [CrossRef]
- Lahner, E.; Pilozzi, E.; Esposito, G.; Galli, G. Gastric carcinoid in the absence of atrophic body gastritis and with low Ki-67 index: A clinical challenge. Scand. J. Gastroenterol. 2014, 49, 506–510. [Google Scholar] [CrossRef]
- Cavalcoli, F.; Zilli, A.; Ciafardini, F.; Massironi, S. Gastric neuroendocrine neoplasms and proton pump inhibitors: Fact orco-incidence? Scand. J. Gastroerol. 2014, 50, 1397–1403. [Google Scholar]
- Sanduleanu, S.; Jonkers, D.; de Bruine, A.; Hameeteman, W. Changes in Gastric mucosa and luminal environment during acid-suppressive therapy: A review in depth. Dig. Liver Dis. 2001, 33, 707–718. [Google Scholar] [CrossRef]
- Kuipers, E.J. Proton Pump Inhibitors and gastric neoplasia. Gut 2006, 55, 1217–1221. [Google Scholar] [CrossRef]
- Ma, C.; Shaheen, A.A.; Congley, S.E.; Andrews, C.N. Interpreting reported risks associated with use of proton pump inhibitors: Residual confounding in a 10-year analysis of national ambulatory data. Gastroenterology 2019. [Google Scholar] [CrossRef] [PubMed]
- Food and Drug Administration. Hypergastrinemia, ECL-cell Hyperplasia and Atrophic Gastritis. FDA Background. Omeprazole magnesium (Prilosec TM) Astra Zeneca with Proctor and Gamble. In Proceedings of the Non-Prescription Drugs Advisory Committee and the Gastrointestinal Drugs Advisory Committee, Gaithersburg, MD, USA, 20 October 2000; Available online: https://wayback.archive-it.org/7993/20170403184623/https://www.fda.gov/ohrms/dockets/ac/00mtbc.htm (accessed on 19 January 2020).
- Hodgson, N.; Koniaris, L.G.; Livingstone, A.S.; Franceschi, D. Gastric Carcinoids. Surg. Endosc. 2005, 19, 1610–1612. [Google Scholar] [CrossRef] [PubMed]
- Maggard, M.A.; O’Connell, J.B.; Ko, C.Y. Updated population-based review of carcinoid tumors. Ann. Surg. 2004, 240, 117–122. [Google Scholar] [CrossRef] [PubMed]
- Modlin, I.M.; Lye, K.D.; Kidd, M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003, 97, 934–950. [Google Scholar] [CrossRef] [PubMed]
- Waldum, H.L.; Oberg, K.; Sandvik, A.K.; Gustafsson, B.I. Not only stem cells, but also mature cells, particularly neuroendocrine cells, may develop into tumors: Time for a paradigm shift. Ther. Adv. Gastroenterol. 2018. [Google Scholar] [CrossRef]
- Cheung, K.S.; Leung, W.K. long-term use of proton pump inhibitors and risk of gastric cancer: A review of the current evidence. Ther. Adv. Gastroenterol. 2019, 2, 1–11. [Google Scholar] [CrossRef]
- Waldum, H.L.; Rehfeld, J.F. Gastric cancer and gastrin: On the interaction of Helicobacter gastritis and acid-inhibitory induced hypergastrinemia. Scand. J. Gastroenterol. 2019, 54, 1118–1123. [Google Scholar] [CrossRef]
- Tran-Duy, A.; Spaetgens, B.; Hoes, A.W.; de Wit, N.J.; Stehouwer, C.D. Use of proton pump inhibitors and risk of fundic gland polyps and gastric cancer: Systematic review and meta-analysis. Clin. Gastroenterol. Hepatol. 2016, 14, 1706–1719. [Google Scholar] [CrossRef]
- Brusselaers, N.; Wahlin, K.; Engstrand, L.; Lagergren, J. Maintenance therapy with proton pump inhibitors and risk of gastric cancer: A nationwide population-based cohort study in Sweden. BMJ Open 2017, e017739. [Google Scholar] [CrossRef]
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McCarthy, D.M. Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids—What Is the Relationship? Int. J. Mol. Sci. 2020, 21, 662. https://doi.org/10.3390/ijms21020662
McCarthy DM. Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids—What Is the Relationship? International Journal of Molecular Sciences. 2020; 21(2):662. https://doi.org/10.3390/ijms21020662
Chicago/Turabian StyleMcCarthy, Denis M. 2020. "Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids—What Is the Relationship?" International Journal of Molecular Sciences 21, no. 2: 662. https://doi.org/10.3390/ijms21020662
APA StyleMcCarthy, D. M. (2020). Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids—What Is the Relationship? International Journal of Molecular Sciences, 21(2), 662. https://doi.org/10.3390/ijms21020662