New methods Clinical endoscopy| Volume 84, ISSUE 3, P512-517, September 2016

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Innovative gastric endoscopic muscle biopsy to identify all cell types, including myenteric neurons and interstitial cells of Cajal in patients with idiopathic gastroparesis: a feasibility study (with video)

Published:April 26, 2016DOI:

      Background and Aims

      The pathophysiology of some GI neuromuscular diseases remains largely unknown. This is in part due to the inability to obtain ample deep gastric wall biopsies that include the intermuscular layer of the muscularis propria (MP) to evaluate the enteric nervous system, interstitial cells of Cajal (ICCs), and related cells. We report on a novel technique for gastric endoscopic muscle biopsy (gEMB).


      Patients with idiopathic gastroparesis were prospectively enrolled in a feasibility study by using a novel “no hole” gEMB. Main outcome measures were technical success, adverse events, and histologic confirmation of the intermuscular layer, including myenteric neurons and ICC. The gEMB was a double resection clip-assist technique. A site was identified on the anterior wall of the gastric body as recommended by the International Working Group on histologic techniques. EMR was performed to unroof and expose the underlying MP. The exposed MP was then retracted into the cap of an over-the-scope clip. The clip was deployed, and the pseudopolyp of MP created was resected. This resulted in a no-hole gEMB.


      Three patients with idiopathic gastroparesis underwent gEMB. Patients had severe delayed gastric emptying with a mean (± standard deviation [SD]) of 49 ± 16.8% of retained gastric contents at 4 hours. They had no history of gastric or small-bowel surgery and did not use steroids or other immunosuppressive drugs. The gEMB procedure was successfully performed, with no procedural adverse events. Postprocedural abdominal pain was controlled with nonsteroidal anti-inflammatory agents and opioid analgesics. Mean length of resected MP was 10.3 ± 1.5 mm. Mean procedure time was 25.7 ± 6 minutes. Hematoxylin and eosin (H&E) staining of tissue samples confirmed the presence of both inner circular and outer longitudinal muscle, as well as the intermuscular layer. H&E staining showed reduced myenteric ganglia in 1 patient. In 2 patients, specialized immunohistochemistry was performed, which showed a marked decrease in myenteric neurons as delineated by an antibody to protein gene product 9.5 and a severe decrease in ICC levels across the muscle layers. At 1 month follow-up, upper endoscopy showed a well-healed scar in 2 patients and minimal ulceration with a retained clip in 1 patient. CT of the abdomen confirmed the integrity of the gastric wall in all patients. Because of lack of an immune infiltrate in the resected samples, patients were not considered suitable for immunosuppressive or steroid therapy.


      gEMB is feasible and easy to perform, with acquisition of tissue close to surgical samples to identify myenteric ganglia, ICCs, and multiple cell types. The ability to perform gEMB represents a paradigm shift in endoscopic tissue diagnosis of gastric neuromuscular pathologies.


      gEMB (gastric endoscopic muscle biopsy), ICC (interstitial cells of Cajal), MP (muscularis propria)
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        • Farrugia G.
        Interstitial cells of Cajal in health and disease.
        Neurogastroenterol Motil. 2008; 20: 54-63
        • Harberson J.
        • Thomas R.M.
        • Harbison S.P.
        • et al.
        Gastric neuromuscular pathology in gastroparesis: analysis of full-thickness antral biopsies.
        Dig Dis Sci. 2010; 55: 359-370
        • Faussone-Pellegrini M.S.
        • Grover M.
        • Pasricha P.
        • et al.
        Ultrastructural differences between diabetic and idiopathic gastroparesis.
        J Cell Mol Med. 2012; 16: 1573-1581
        • Angeli T.R.
        • Cheng L.K.
        • Du P.
        • et al.
        Loss of interstitial cells of Cajal and patterns of gastric dysrhythmia in patients with chronic unexplained nausea and vomiting.
        Gastroenterology. 2015; 149: 56-66
        • Cirillo C.
        • Bessissow T.
        • Desmet A.S.
        • et al.
        Evidence for neuronal and structural changes in submucous ganglia of patients with functional dyspepsia.
        Am J Gastroenterol. 2015; 110: 1205-1215
        • Knowles C.H.
        • De Giorgio R.
        • Kapur R.P.
        • et al.
        Gastrointestinal neuromuscular pathology: guidelines for histological techniques and reporting on behalf of the Gastro 2009 International Working Group.
        Acta Neuropathol. 2009; 118: 271-301
        • Kashyap P.
        • Farrugia G.
        Enteric autoantibodies and gut motility disorders.
        Gastroenterol Clin North Am. 2008; 37: 397-410
        • Kashyap P.
        • Farrugia G.
        Diabetic gastroparesis: what we have learned and had to unlearn in the past 5 years.
        Gut. 2010; 59: 1716-1726
        • Pasricha P.J.
        • Yates K.P.
        • Nguyen L.
        • et al.
        Outcomes and factors associated with reduced symptoms in patients with gastroparesis.
        Gastroenterology. 2015; 149: 1762-1774
        • Neshatian L.
        • Gibbons S.J.
        • Farrugia G.
        Macrophages in diabetic gastroparesis—the missing link?.
        Neurogastroenterol Motil. 2015; 27: 7-18
        • Grover M.
        • Farrugia G.
        • Lurken M.S.
        • et al.
        • NIDDK Gastroparesis Clinical Research Consortium
        NIDDK Gastroparesis Clinical Research Consortium. Cellular changes in diabetic and idiopathic gastroparesis.
        Gastroenterology. 2011; 140: 1575-1585
        • Rajan E.
        • Gostout C.J.
        • Lurken M.S.
        • et al.
        Evaluation of endoscopic approaches for deep gastric-muscle-wall biopsies: What works?.
        Gastrointest Endosc. 2008; 67: 297-303
        • Rajan E.
        • Gostout C.J.
        • Aimore Bonin E.
        • et al.
        Endoscopic full-thickness biopsy of the gastric wall with defect closure by using an endoscopic suturing device: survival porcine study.
        Gastrointest Endosc. 2012; 76: 1014-1019
        • Rajan E.
        • Gostout C.J.
        • Lurken M.S.
        • et al.
        Endoscopic “no hole” full-thickness biopsy of the stomach to detect myenteric ganglia.
        Gastrointest Endosc. 2008; 68: 301-307
        • Andrews C.N.
        • Mintchev P.
        • Neshev E.
        • et al.
        Percutaneous endoscopically assisted transenteric full-thickness gastric biopsy: initial experience in humans.
        Gastrointest Endosc. 2011; 73: 949-954
        • Othman M.O.
        • Davis B.
        • Saroseik I.
        • et al.
        EUS-guided FNA biopsy of the muscularis propria of the antrum in patients with gastroparesis is feasible and safe.
        Gastrointest Endosc. 2016; 83: 327-333
        • Grover M.
        • Farrugia G.
        • Pasricha P.J.
        Endoscopy of the “brain”: the next frontier in gastroenterology.
        Gastrointest Endosc. 2016; 83: 334-336
        • Sumiyama K.
        • Kiesslich R.
        • Ohya T.R.
        • et al.
        In vivo imaging of enteric neuronal networks in humans using confocal laser endomicroscopy.
        Gastroenterology. 2012; 143: 1152-1153
        • Ohya T.R.
        • Sumiyama K.
        • Takahashi-Fujigasaki J.
        • et al.
        In vivo histologic imaging of the muscularis propria and myenteric neurons with probe-based confocal laser endomicroscopy in porcine models (with videos).
        Gastrointest Endosc. 2012; 75: 405-410
        • Pasricha P.J.
        Endoscopy 20 years into the future.
        Clin Gastroenterol Hepatol. 2013; 11: 119-122
        • Boesmans W.
        • Hao M.M.
        • Vanden Berghe P.
        Optical tools to investigate cellular activity in the intestinal wall.
        J Neurogastroenterol Motil. 2015; 21: 337-351
        • Grover M.
        • Bernard C.E.
        • Pasricha P.J.
        • et al.
        Clinical-histological associations in gastroparesis: results from the Gastroparesis Clinical Research Consortium.
        Neurogastroenterol Motil. 2012; 24 (E249): 531-539