Multifocal Gastric Carcinoid Tumor in a Patient with Pernicious Anemia Receiving Lansoprazole

Attila, Tan; Santharam, Raj; Blom, Dennis; Komorowski, Richard; Koch, Timothy R.

doi:10.1007/s10620-005-2466-3

Cited by 7 publications

(7 citation statements)

References 17 publications

(14 reference statements)

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“…From the earliest report [35] in 1998, there has been progressive expansion in the amount of detail provided on each case that allows increasingly critical evaluation of the evidence presented. Review of each case by this author, in the light of current knowledge, may not agree with the conclusion of the original author(s) in all cases: for instance, while Appendix A case #3 [37] was alleged to occur in a patient with pernicious anemia (an obvious confounder), other details presented in the publication cast serious doubt that this condition was present. Similarly, while authors of case #7 [40] discussed classifying that case as a type-3 g-NET, this was invalid because serum gastrin was not measured before excising the tumor and discontinuing PPI therapy: from other described cases serum gastrin would be expected to be normal by the time the patient was tested, thus defying accurate classification.…”

Section: Evidence Of Causationmentioning

confidence: 81%

“…There are now eleven cases reported in whom gastric carcinoid (g-NET) tumors developed while the patient was using a PPI, and in whom evidence of ZES/MEN-1 or gastric oxyntic mucosal atrophy was lacking [12,[35][36][37][38][39][40][41]. In the interests of space, brief summaries of each case are attached as an Appendix A.…”

Section: Evidence Of Causationmentioning

confidence: 99%

“…Histochemichal staining of tumor biopsies revealed the presence of chromogranin A and synaptophysin. No follow-up data was provided [37]. # 4.…”

Section: Appendix a Gastric Carcinoids Associated With The Use Of Ppmentioning

confidence: 99%

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Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids—What Is the Relationship?

McCarthy

2020

IJMS

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Neuroendocrine tumors (NETs) throughout the body are the focus of much current interest. Most occur in the gastrointestinal tract and have shown a major increase in incidence over the past 30 years, roughly paralleling the world-wide increase in the use of proton pump inhibitor (PPI) drugs. The greatest rise has occurred in gastric carcinoids (g-NETs) arising from enterochromaffin-like (ECL) cells. These tumors are long known to occur in auto-immune chronic atrophic gastritis (CAG) and Zollinger-Ellison syndrome (ZES), with or without multiple endocrine neoplasia type-1 (MEN-1), but the incidences of these conditions do not appear to have increased over the same time period. Common to these disease states is persistent hypergastrinemia, generally accepted as causing g-NETs in CAG and ZES, and postulated as having similar tumorigenic effects in PPI users. In efforts to study the increase in their occurrence, g-NETs have been classified in a number of discussed ways into different grades that differ in their incidence and apparent pathogenesis. Based on a large amount of experimental data, tumorigenesis is mediated by gastrin’s effects on the CCK2R-receptor on ECL-cells that in turn leads to hyperplasia, dysplasia, and finally neoplasia. However, in all three conditions, the extent of response of ECL-cells to gastrin is modified by a number of genetic influences and other underlying risk factors, and by the duration of exposure to the hormonal influence. Data relating to trophic effects of hypergastrinemia due to PPI use in humans are reviewed and, in an attached Appendix A, all 11 reports of g-NETs that occurred in long-term PPI users in the absence of CAG or ZES are summarized. Mention of additional suspected cases reported elsewhere are also listed. Furthermore, the risk in humans may be affected by the presence of underlying conditions or genetic factors, including their PPI-metabolizer phenotype, with slow metabolizers likely at increased risk. Other problems in estimating the true incidence of g-NETs are discussed, relating to non-reporting of small tumors and failure of the Surveillance, Epidemiology, and End Results Program (SEER) and other databases, to capture small tumors or those not accorded a T1 rating. Overall, it appears likely that the true incidence of g-NETs may be seriously underestimated: the possibility that hypergastrinemia also affects tumorigenesis in additional gastrointestinal sites or in tumors in other organ systems is briefly examined. Overall, the risk of developing a g-NET appears greatest in patients who are more than 10 years on drug and on higher doses: those affected by chronic H. pylori gastritis and/or consequent gastric atrophy may also be at increased risk. While the overall risk of g-NETs induced by PPI therapy is undoubtedly low, it is real: this necessitates caution in using PPI therapy for long periods of time, particularly when initiated in young subjects.

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Section: Evidence Of Causationmentioning

confidence: 81%

Section: Evidence Of Causationmentioning

confidence: 99%

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Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids—What Is the Relationship?

McCarthy

2020

IJMS

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“…Although it is more potent than omeprazole [69], recent studies have shown that it may have serious side effects in humans and animals as well [70][71][72]. Rabeprazole, also a substituted benzimidazole, inhibits gastric acid secretion.…”

Section: Proton Pump Blockersmentioning

confidence: 99%

Reactive Oxygen Species-Induced Gastric Ulceration: Protection By Melatonin

Bandyopadhyay¹,

Chattopadhyay

2006

CMC

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Gastric hyperacidity and ulceration of the stomach mucosa due to various factors are serious health problems of global concern. Although the mechanism of acid secretion from the parietal cells is now well understood, the processes involved in gastric ulceration are still not clear. Among the various causes of gastric ulceration, lesions caused by stress, alcohol consumption, Helicobacter pylori and due to use of non-steroidal anti-inflammatory drugs have been shown to be mediated largely through the generation of reactive oxygen species, especially the hydroxyl radical. A number of excellent drugs, developed over the decades, have proven useful in controlling hyperacidity and ulceration although their long-term use is reported to be associated with various side effects. Hence the investigations continue with an objective to find a compound possessing anti-secretory, anti-ulcer and antioxidant properties which will serve as a therapeutic agent to reduce gastric hyperacidity and ulcers. This article describes the role of reactive oxygen species in gastric ulceration, briefly presents a note on the currently available drugs controlling them, and focuses on the role of melatonin, a pineal secretory product, in protecting against gastric lesions. In experimental studies, melatonin has been shown to be effective in reducing mucosal breakdown and ulcer formation in a wide variety of situations. Additionally, the low toxicity of melatonin supports further investigation of this molecule as a promising gastro-protective agent. Finally, we include a commentary on how melatonin research with respect to gastric pathophysiology can move forward with a view to eventually using this indole as a therapeutic agent alone or in combination with the existing drugs to control gastric ulceration in humans in order to increase their efficacy and/or to reduce their side effects.

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“…Thus, in patients received long-term acid inhibiton treatment, another concern is the increased gastric carcinoid risk. In fact, sporadic gastric carcinoid cases have been reported in patients exposed to longterm PPI treatments [60,61] . Long-term safety is still of high concern.…”

Section: The Clinical Significance Of Ecl Cell Activation In Long-termentioning

confidence: 99%

Physiological and clinical significance of enterochromaffin-like cell activation in the regulation of gastric acid secretion

Cui

Waldum²

2007

WJG

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Gastric acid plays an important role in digesting food (especially protein), iron absorption, and destroying swallowed micro-organisms. H+ is secreted by the oxyntic parietal cells and its secretion is regulated by endocrine, neurocrine and paracrine mechanisms. Gastrin released from the antral G cell is the principal physiological stimulus of gastric acid secretion. Activation of the enterochromaffin-like (ECL) cell is accepted as the main source of histamine participating in the regulation of acid secretion and is functionally and trophically controlled by gastrin, which is mediated by gastrin/CCK-2 receptors expressed on the ECL cell. However, long-term hypergastrinemia will induce ECL cell hyperplasia and probably carcinoids. Clinically, potent inhibitors of acid secretion have been prescribed widely to patients with acid-related disorders. Long-term potent acid inhibition evokes a marked increase in plasma gastrin levels, leading to enlargement of oxyntic mucosa with ECL cell hyperplasia. Accordingly, the induction of ECL cell hyperplasia and carcinoids remains a topic of considerable concern, especially in long-term use. In addition, the activation of ECL cells also induces another clinical concern, i.e., rebound acid hypersecretion after acid inhibition. Recent experimental and clinical findings indicate that the activation of ECL cells plays a critical role both physiologically and clinically in the regulation of gastric acid secretion.

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Multifocal Gastric Carcinoid Tumor in a Patient with Pernicious Anemia Receiving Lansoprazole

Cited by 7 publications

References 17 publications

Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids—What Is the Relationship?

Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids—What Is the Relationship?

Reactive Oxygen Species-Induced Gastric Ulceration: Protection By Melatonin

Physiological and clinical significance of enterochromaffin-like cell activation in the regulation of gastric acid secretion

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