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Reconsideration of the Gastroparetic Syndrome

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Abstract

Purpose of Review

Gastroparesis is a chronic disorder characterized by a constellation of foregut symptoms, including postprandial nausea, vomiting, distension, epigastric pain, and regurgitation in the absence of gastric outlet obstruction. Despite considerable research over the past decades, there remains to be only nominal understanding of disease classification, diagnostic criteria, pathogenesis, and preferred therapy.

Recent Findings

We critically reassess current approaches for disease identification and stratification, theories of causation, and treatment for gastroparesis. Gastric scintigraphy, long considered a diagnostic standard, has been re-evaluated in light of evidence showing low sensitivity, whereas newer testing modalities are incompletely validated. Present concepts of pathogenesis do not provide a unified model linking biological impairments with clinical manifestations, whereas available pharmacological and anatomical treatments lack explicit selection criteria or evidence for sustained effectiveness. We propose a disease model that embodies the re-programming of distributed neuro-immune interactions in the gastric wall by inflammatory perturbants. These interactions, combined with effects on the foregut hormonal milieu and brain-gut axis, are postulated to generate the syndromic attributes characteristically linked with gastroparesis.

Summary

Research linking models of immunopathogenesis with diagnostic and therapeutic paradigms will lead to reclassifications of gastroparesis that guide future trials and technological developments.

Key points

• The term gastroparesis embodies a heterogenous array of symptoms and clinical findings based on a complex assimilation of afferent and efferent mechanisms, gastrointestinal locations, and pathologies.

• There currently exists no single test or group of tests with sufficient capacity to be termed a definitional standard for gastroparesis.

• Present research regarding pathogenesis suggests the importance of immune regulation of intrinsic oscillatory activity involving myenteric nerves, interstitial cells of Cajal, and smooth muscle cells.

• Prokinetic pharmaceuticals remain the mainstay of management, although novel treatments are being studied that are directed to alternative muscle/nerve receptors, electromodulation of the brain-gut axis, and anatomical (endoscopic, surgical) interventions.

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Authors and Affiliations

  1. Research Service, Providence VA Medical Center, Providence, RI, USA

    Richard J. Gilbert, Jamila H. Siamwala, Vivek Kumar, Christopher C. Thompson & Scott A. Shikora

  2. Department of Molecular Physiology, Pharmacology, and Biotechnology, Warren Alpert Medical School of Brown University, Providence, RI, USA

    Richard J. Gilbert, Jamila H. Siamwala, Vivek Kumar, Christopher C. Thompson & Scott A. Shikora

  3. Division of Gastroenterology and Departments of Medicine and Surgery, Brigham and Women’s Hospital, Boston, MA, USA

    Richard J. Gilbert, Jamila H. Siamwala, Vivek Kumar, Christopher C. Thompson & Scott A. Shikora

  4. Ocean State Research Institute, Providence VA Medical Center, 830 Chalkstone Ave, Providence, RI, 02908, USA

    Richard J. Gilbert

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Contributions

RJG was the principal author, having performed all analyses of the literature, generated the initial draft and concepts underlying the pathogenesis model and contributed substantially to the editing of all versions.

JHS contributed substantially to editing and revisions to all versions of the manuscript and was responsible for the generation of the immunopathogenesis section.

VK contributed substantially to the editing and revisions made to all versions of the manuscript and made significant contributions to the analyses of pathogenesis shown in text, tables, and figures.

CCT contributed substantially to the editing and revisions made to all versions of the manuscrip and made significant contributions to the analysis of the literature related to endoscopic therapy.

SAS participated in the conceptualization of the manuscript, contributed significantly to the editing and revisions, and made significant contributions to the analysis related to anatomic treatment.

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Correspondence to Richard J. Gilbert.

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RJG, JHS, VK, and SAS have no conflicts or appearances of conflict to report relevant to the content of this manuscript. CCT discloses the following potentially competing interests related to endoscopic treatments for GI disorders, including research support/consulting from Apollo Endo-surgery, Aspire Bariatrics, Boston Scientific, Erbe, GI Dynamics, Lumendi, Olympus, USGI Medical, and Covidien/Medtronic, as well as equity interest in Enterasense and Envision.

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Gilbert, R.J., Siamwala, J.H., Kumar, V. et al. Reconsideration of the Gastroparetic Syndrome. Curr Gastroenterol Rep 25, 75–90 (2023). https://doi.org/10.1007/s11894-023-00865-w

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