Morphometric evaluation of oesophageal wall in patients with nutcracker oesophagus and ineffective oesophageal motility

Abstract

The pathogenesis of nutcracker oesophagus (NE) and ineffective oesophageal motility (IEM) is unclear. Damage to the enteric nervous system or smooth muscle can cause oesophageal dysmotility. We tested the hypothesis that NE and IEM are associated with abnormal muscular or neural constituents of the oesophageal wall. Oesophageal manometry was performed in patients prior to total gastrectomy for gastric cancer. The oesophageal manometries were categorized as normal (n = 7), NE (n = 13), or IEM (n = 5). Histologic examination of oesophageal tissue obtained during surgery was performed after haematoxylin and eosin (H&E) and trichrome staining. Oesophageal innervation was examined after immunostaining for protein gene product-9.5 (PGP-9.5), choline acetyltransferase (ChAT) and neuronal nitric oxide synthase (nNOS). There were no significant differences in inner circular smooth muscle thickness or degree of fibrosis among the three groups. Severe muscle fibre loss was found in four of five patients with IEM. The density of PGP-9.5-reactive neural structures was not different among the three groups. The density of ChAT immunostaining in the myenteric plexus (MP) was significantly greater in patients with NE (P < 0.05) and the density of nNOS immunostaining in the circular muscle (CM) was significantly greater in IEM patients (P < 0.05). The ChAT/nNOS ratio in both MP and CM was significantly greater in NE patients. NE may result from an imbalance between the excitatory and inhibitory innervation of the oesophagus, because more than normal numbers of ChAT-positive myenteric neurones are seen in NE. Myopathy and/or increased number of nNOS neurones may contribute to the hypocontractile motor activity of IEM.

Pharmacologic Specificity of Nicotinic Receptor-Mediated Relaxation of Muscarinic Receptor Precontracted Human Gastric Clasp and Sling Muscle Fibers within the Gastroesophageal Junction

“…The latter two areas were not studied here because our focus was on the possible location of neurons within the muscle strips that were examined physiologically. Our findings in the LEC region also match those by Kim et al (2008), who observed Pgp9.5 neuronal structures buried within muscular layers of esophageal wall of patients with esophageal myopathies. Because our and Kim's studies are the first to examine the location of neuronal structures in the GEJ of humans using specific neuronal markers, perhaps the location of these neurons are in fact not atypical but the norm.…”

Evaluation of Esophageal Motility Utilizing the Functional Lumen Imaging Probe

“…(28) Alternatively, as all five of these patients demonstrated RRCs, the potential remains that hypercontractility (and retrograde contractions as a response to distension) are related to an imbalance of inhibitory and excitatory neural regulation. (29, 30) Future studies evaluating a greater number of asymptomatic controls and patients with HRM-defined spastic motor disorders, as well as patients with mechanical esophageal obstruction, will clarify the clinical significance of RRCs and aid refinement of the FLIP topography motility classification.…”

Lymphocytic Esophagitis in Nonachalasia Primary Esophageal Motility Disorders

“…That the pathogenesis of PMED and achalasia may be related, is supported by transition of nutcracker esophagus(21, 22) and diffuse spasm(23, 24) to achalasia and by myenteric lymphocytic inflammation in the distal esophagus of 23% (3/13) of patients with nutcracker esophagus. (25)…”