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)

Abstract

Background and Aims The pathophysiology of some gastrointestinal neuromuscular diseases (GINMD) 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 (ICC) and related cells. We report on a novel technique for gastric endoscopic muscle biopsy (gEMB). Methods Patients with idiopathic gastroparesis were prospectively enrolled in a feasibility study using a novel “no hole” gEMB. Main outcome measures were technical success, adverse events and histological 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 histological techniques. Endoscopic mucosal resection 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 “nohole” gEMB. Results Three patients with idiopathic gastroparesis underwent gEMB. Patients had severe delayed gastric emptying with a mean 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. Postprocedure 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. Tissue samples on hematoxylin and eosin (H&E) stain confirmed presence of both inner circular and outer longitudinal muscle as well as the intermuscular layer. H&E stain showed reduced myenteric ganglia in 1 patient. In 2 patients, specialized immunohistochemistry was performed, which showed marked decrease in myenteric neurons as delineated by an antibody to Protein Gene Product (PGP) 9.5 and severe decrease in ICC across the muscle layers. At 1 month follow-up, upper endoscopy showed a well-healed scar in 2 patients and minimal ulceration with retained clip in 1 patient. CT abdomen confirmed the integrity of the gastric wall in all patients. Due to lack of an immune infiltrate in the resected samples, patients were not considered suitable for immunosuppressive or steroid therapy. Conclusions gEMB is feasible and easy to perform, with acquisition of tissue close to surgical samples to identify myenteric ganglia, ICC and multiple cell types. The ability to perform gEMB represents a paradigm shift in endoscopic tissue diagnosis of gastric neuromuscular pathologies.

Advances in the diagnosis and classification of gastric and intestinal motility disorders

“…For the stomach, there are only preliminary data suggesting that histological findings can guide treatment 104 . An endoscopic method to obtain myenteric plexus samples for histopathological assessment has been described 105 .…”

Endoscopic versus Laparoscopic Full-Thickness Biopsy in the Pathological Evaluation of the Enteric Nervous System

“…Previous biopsy samplings at our department did not lead to any complications [ 19 ]. An alternative endoscopic device with mainly submucosal biopsy sampling has also recently been presented, to avoid laparoscopic sampling [ 20 ].…”

Submucosal Tunneling Muscle Biopsy for Esophageal Motility Disorders: A Case Report

“…Myenteric plexus is not homogenous in the entire length of the esophagus and has ganglia at different distances from each other, thus the size of the biopsy material must be sufficient. 5,6 According to the literature, endoscopic ultrasound-guided fine-needle aspiration is a safe and effective method, although there are some limitations: parts of the muscular layer are fragmented and it is difficult to correctly place the obtained specimens for a meaningful histological investigation. 7 Considering the limitations of the techniques mentioned above, we propose the tunneling method as a safe method to perform biopsy with a direct visual control of the region of interest.…”