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      Is Interstitial Cells of Cajal–opathy Present in Gastroparesis?

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          Abstract

          Gastroparesis (GP), defined as delayed gastric emptying in the absence of any mechanical obstruction, is a challenging clinical condition, mainly because of limited treatment options. Studies in animal models of delayed gastric emptying as well as patients with gastroparesis revealed depletion or ultrastructural changes of interstitial cells of Cajal (ICC) in the gastric tissue, recently termed ICC-opathy. ICC are the pacemakers of the gastrointestinal tract and are involved in the transmission of the neuronal signaling to the smooth muscles. Therefore, lack of ICC could be one explanation of delayed gastric emptying in gastroparetic patients. How frequently ICC changes are observed in gastroparesis is not yet clear. In this review, the data on gastric ICC counts and morphology in animal models and patients with gastroparesis are discussed.

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          The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006.

          Lawrence A Szarka, Brian Mullan, Nicholas J. Talley … (2009)
          The epidemiology of gastroparesis is unknown. We aimed to determine the incidence, prevalence, and outcome of gastroparesis in the community. Using the Rochester Epidemiology Project, a medical records linkage system in Olmsted County, Minnesota, we identified county residents with potential gastroparesis. The complete medical records were reviewed by a gastroenterologist. Three diagnostic definitions were used: (1) definite gastroparesis, delayed gastric emptying by standard scintigraphy and typical symptoms for more than 3 months; (2) probable gastroparesis, typical symptoms and food retention on endoscopy or upper gastrointestinal study; (3) possible gastroparesis, typical symptoms alone or delayed gastric emptying by scintigraphy without gastrointestinal symptoms. Poisson regression was used to assess the association of incidence rates with age, sex, and calendar period. Among 3604 potential cases of gastroparesis, 83 met diagnostic criteria for definite gastroparesis, 127 definite plus probable gastroparesis, and 222 any of the 3 definitions of gastroparesis. The age-adjusted (to the 2000 US white population) incidence per 100,000 person-years of definite gastroparesis for the years 1996-2006 was 2.4 (95% confidence interval [CI], 1.2-3.8) for men and 9.8 (95% CI, 7.5-12.1) for women. The age-adjusted prevalence of definite gastroparesis per 100,000 persons on January 1, 2007, was 9.6 (95% CI, 1.8-17.4) for men and 37.8 (95% CI, 23.3-52.4) for women. Overall survival was significantly lower than the age- and sex-specific expected survival computed from the Minnesota white population (P<.05). Gastroparesis is an uncommon condition in the community but is associated with a poor outcome.
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            Abnormal initiation and conduction of slow-wave activity in gastroparesis, defined by high-resolution electrical mapping.

            Andrew J Pullan, Timothy R Angeli, Gregory O'Grady … (2012)
            Interstitial cells of Cajal (ICC) generate slow waves. Disrupted ICC networks and gastric dysrhythmias are each associated with gastroparesis. However, there are no data on the initiation and propagation of slow waves in gastroparesis because research tools have lacked spatial resolution. We applied high-resolution electrical mapping to quantify and classify gastroparesis slow-wave abnormalities in spatiotemporal detail. Serosal high-resolution mapping was performed using flexible arrays (256 electrodes; 36 cm(2)) at stimulator implantation in 12 patients with diabetic or idiopathic gastroparesis. Data were analyzed by isochronal mapping, velocity and amplitude field mapping, and propagation animation. ICC numbers were determined from gastric biopsy specimens. Mean ICC counts were reduced in patients with gastroparesis (2.3 vs 5.4 bodies/field; P < .001). Slow-wave abnormalities were detected by high-resolution mapping in 11 of 12 patients. Several new patterns were observed and classified as abnormal initiation (10/12; stable ectopic pacemakers or diffuse focal events; median, 3.3 cycles/min; range, 2.1-5.7 cycles/min) or abnormal conduction (7/10; reduced velocities or conduction blocks; median, 2.9 cycles/min; range, 2.1-3.6 cycles/min). Circumferential conduction emerged during aberrant initiation or incomplete block and was associated with velocity elevation (7.3 vs 2.9 mm s(-1); P = .002) and increased amplitudes beyond a low base value (415 vs 170 μV; P = .002). High-resolution mapping revealed new categories of abnormal human slow-wave activity. Abnormalities of slow-wave initiation and conduction occur in gastroparesis, often at normal frequency, which could be missed by tests that lack spatial resolution. Irregular initiation, aberrant conduction, and low amplitude activity could contribute to the pathogenesis of gastroparesis. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
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              Risk of gastroparesis in subjects with type 1 and 2 diabetes in the general population.

              A Zinsmeister, G Locke, Rok Choung … (2011)
              In patients with diabetes mellitus (DM) and upper gastrointestinal symptoms, a diagnosis of diabetic gastroparesis is often considered, but population-based data on the epidemiology of diabetic gastroparesis are lacking. We aimed to estimate the frequency of and risk factors for gastroparesis among community subjects with DM. In this population-based, historical cohort study, the medical records linkage system of the Rochester Epidemiology Project was used to identify 227 Olmsted County, MN residents with type 1 DM in 1995, a random sample of 360 residents with type 2 DM, and an age- and sex-stratified random sample of 639 nondiabetic residents. Using defined diagnostic criteria, we estimated the subsequent risk of developing gastroparesis in each group through 2006. The risk in DM, compared with frequency-matched community controls, was assessed by Cox proportional hazards modeling. The cumulative proportions developing gastroparesis over a 10-year time period were 5.2% in type 1 DM, 1.0% in type 2 DM, and 0.2% in controls. The age- and gender-adjusted hazard ratios (HRs) for gastroparesis (relative to controls) was 33 (95% confidence interval (CI): 4.0, 274) in type 1 DM and 7.5 (95% CI: 0.8, 68) in type 2 DM. The risk of gastroparesis in type 1 DM was significantly greater than in type 2 DM (HR: 4.4 (1.1, 17)). Heartburn (HR: 6.6 (1.7, 25)) at baseline was associated with diabetic gastroparesis in type 1 DM. Gastroparesis is relatively uncommon in patients with DM, although an increased risk for gastroparesis was observed in type 1 DM.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Neurogastroenterol Motil
                Journal ID (iso-abbrev): J Neurogastroenterol Motil
                Title: Journal of Neurogastroenterology and Motility
                Publisher: Korean Society of Neurogastroenterology and Motility
                ISSN (Print): 2093-0879
                ISSN (Electronic): 2093-0887
                Publication date (Print): October 2015
                Publication date (Electronic): 31 October 2015
                Volume: 21
                Issue: 4
                Pages: 486-493
                Affiliations
                Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
                Author notes
                [* ]Correspondence: Richard W McCallum, MD, FACP, FRACP (AUST), FACG, AGAF, Department of Internal Medicine, Center for Neurogastroenterology and GI Motility, 4800 Alberta Avenue, El Paso, TX 79905, USA, Tel: +1-915-215-5218, Fax: +1-915-545-6634, E-mail: richard.mccallum@ 123456ttuhsc.edu
                Article
                Publisher ID: jnm-21-486
                DOI: 10.5056/jnm15075
                PMC ID: 4622130
                PubMed ID: 26424037
                SO-VID: 2a6ca080-1cd4-4f62-a2b3-cd861bb70ce9
                Copyright © © 2015 The Korean Society of Neurogastroenterology and Motility
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 05 May 2015
                Date revision received : 22 July 2015
                Date accepted : 07 August 2015
                Categories
                Subject: Review

                ScienceOpen disciplines: Neurology
                Keywords: gastroparesis,interstitial cells of cajal,physiopathology
                Data availability:
                ScienceOpen disciplines: Neurology
                Keywords: gastroparesis, interstitial cells of cajal, physiopathology

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