Abstract

The aim was to assess methods utilized in assessing mast cell involvement in functional abdominal pain disorders (FAPDs), specifically to describe variability in methods utilized to assess both mast cell density and activation and determine if a consensus exists. After a literature search identified 70 manuscripts assessing mast cell density, data were extracted including FAPD diagnosis, site of biopsy, selection of microscopic fields analyzed, selection of mucosal region analyzed, method of mast cell identification, method to assess mast cell density, and if performed, method to assess mast cell activation. There appears to be some consensus favoring inmmunohistochemical stains over histochemical stains for identifying mast cells. Otherwise, considerable variability exists in methodology for assessing mast cell density and activation. Regardless of method, approximately 80% of studies found increased mast cell density and/or activation in comparison to controls with no method being superior. A wide variety of methods have been employed to assess mast cell density and activation with no well-established consensus and inadequate data to recommend specific approaches. The current methodology providing physiologic information needs to be translated to a standard methodology providing clinical information with the development of criteria establishing abnormal density and/or activation, and more importantly, predicting treatment response.

Highlights

  • Functional abdominal pain disorders (FAPDs), irritable bowel syndrome (IBS) and functional dyspepsia (FD), are highly prevalent conditions resulting in significant morbidity and healthcare costs worldwide

  • Mast cells have been implicated in both IBS and FD, in part due to their location at the interface between the patient and the environment and in part due to their functional connectivity to the multiple systems implicated in the generation of gastrointestinal symptoms [3]

  • The aim of the current survey was to assess the methods utilized in assessing mast cell involvement in FAPDs in both adults and children, to describe variability in methods utilized to assess both mast cell density and activation and determine if there appears to be any consensus

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Summary

Introduction

Functional abdominal pain disorders (FAPDs), irritable bowel syndrome (IBS) and functional dyspepsia (FD), are highly prevalent conditions resulting in significant morbidity and healthcare costs worldwide. A variety of methods are available to assess mast cell activation These include measuring (1) degranulation (e.g., utilizing transmission electron microscopy) [10,11,12,13,14,15,16,17,18,19]; (2) mast cell-derived mediators (e.g., tryptase and histamine) in biologic fluids or intestinal tissue either utilizing techniques such as RNA seq or protein analysis [17,18,20,21,22,23]; and, (3) mediators in the supernatant after tissue incubation [16,17,20,24,25,26,27,28,29,30,31,32,33]. The aim of the current survey was to assess the methods utilized in assessing mast cell involvement in FAPDs in both adults and children, to describe variability in methods utilized to assess both mast cell density and activation and determine if there appears to be any consensus. Assessment of current practices represents the first step in this transition

Literature Assessment
Summary of Methods for Mast Cell Evaluation
Method
Findings
Discussion
Conclusions
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