J. L. Conklin

Components of the standard oesophageal manometry

This document originates from several working groups attempting to standardize the performance and interpretation of oesophageal manometry. The authors present an interpretation of the consensus that articulates the established clinical roles for oesophageal manometry and describes the technical components of a basic, standard oesophageal motility examination. Members of the working groups all thought that standardizing oesophageal motility testing is a priority for a number of reasons. Perhaps most important, there is a dearth of standardized training for individual practitioners who perform and interpret oesophageal manometry. Training in these techniques is inadequate in most gastrointestinal (GI) training programmes, and practising clinicians often learn from providers of manometry equipment during brief training sessions. In addition, multiple methods are used for performing and reporting oesophageal manometries, making it difficult or impossible to share data between investigators or clinicians. With the advent of laparoscopic Nissen fundoplication, there has been an explosion of interest in the use of oesophageal manometry as a preoperative diagnostic tool. At the same time, changes in medical practise have placed the conduct of oesophageal manometry into the hands of nurses, medical technicians and others with no prior experience in the techniques or theory of oesophageal manometry. Indeed, their supervising clinicians often have a minimal understanding of oesophageal motor physiology and the technical underpinnings of oesophageal manometry. We have not attempted to address the specific needs for training of the individual performing the tests. It is apparent that these individuals come from a variety of technical or nursing disciplines and are often regulated quite differently by institutional, regional or national licensing authorities. The people undertaking these studies should have a good working knowledge of the principles of oesophageal anatomy and physiology and a thorough understanding of their equipment as a minimum. Participants in our working groups felt that providing a specific and detailed description of the components of a standard oesophageal manometry may help clinical practitioners to perform a standardized and reproducible oesophageal manometry that can be interpreted by others. These guidelines are not meant to supplant the practise of those who have developed their own systems over many years and who are considered experts in the field of oesophageal manometry, nor are they meant to be a detailed, advanced handbook of oesophageal manometry. Those detailed methods can be found in several of the publications or books on the topic. This report comes in three parts: a basic description of the functional information derived from a manometry study, a description of the performance of oesophageal manometry, and a description of the important components of the manometry report. The opinions contained reflect the consensus of the working party derived from the American Motility Society (AMS) and European Society of Neurogastroenterology and Motility Society (ESNM). The conclusions are based on published data and on the combined experience of the participants. Input was also received from several Address for correspondence Dr. Joseph A. Murray, Professor of Medicine, Division of Gastroenterology and Hepatology, The Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Received: 19 February 2003 Accepted for publication: 13 June 2003 Neurogastroenterol Motil (2003) 15, 591–606

Evaluation of esophageal motor function in clinical practice

Esophageal motor function is highly coordinated between central and enteric nervous systems and the esophageal musculature, which consists of proximal skeletal and distal smooth muscle in three functional regions, the upper and lower esophageal sphincters, and the esophageal body. While upper endoscopy is useful in evaluating for structural disorders of the esophagus, barium esophagography, radionuclide transit studies, and esophageal intraluminal impedance evaluate esophageal transit and partially assess motor function. However, esophageal manometry is the test of choice for the evaluation of esophageal motor function. In recent years, high‐resolution manometry (HRM) has streamlined the process of acquisition and display of esophageal pressure data, while uncovering hitherto unrecognized esophageal physiologic mechanisms and pathophysiologic patterns. New algorithms have been devised for analysis and reporting of esophageal pressure topography from HRM. The clinical value of HRM extends to the pediatric population, and complements preoperative evaluation prior to foregut surgery. Provocative maneuvers during HRM may add to the assessment of esophageal motor function. The addition of impedance to HRM provides bolus transit data, but impact on clinical management remains unclear. Emerging techniques such as 3‐D HRM and impedance planimetry show promise in the assessment of esophageal sphincter function and esophageal biomechanics.

The effects of methane and hydrogen gases produced by enteric bacteria on ileal motility and colonic transit time

Background  Gases produced by intestinal flora may modulate intestinal motor function in healthy individuals as well as those with functional bowel disease. Methane, produced by enteric bacteria in the human gut, is associated with slowed intestinal transit and constipation. The effects of hydrogen, another main gas produced by bacterial fermentation in the gut, on small bowel and colonic motor function remains unrecognized. Therefore, we set out to investigate whether intestinal gases including methane and hydrogen could influence the small bowel motility and colonic transit.

The effect of sildenafil on oesophageal motor function in healthy subjects and patients with nutcracker oesophagus

Abstract  Type 5 phosphodiesterase terminates the action of nitric oxide (NO) induced 3′,5′‐cyclic monophosphate (cGMP). Sildenafil inhibits this phosphodiesterase, increases cellular cGMP concentrations and enhances NO‐induced smooth muscle relaxation. We investigated the effect of sildenafil on the oesophageal motor function of healthy subjects and patients with nutcracker oesophagus. Eight healthy volunteers and nine patients with nutcracker oesophagus participated in this study. The participants underwent oesophageal manometries on two separate days after either 20 mL of distilled water or 0.8 mg kg−1 sildenafil dissolved in 20 mL of water was infused into the stomach. Lower oesophageal sphincter (LOS) resting pressure, the duration of LOS relaxation and the amplitudes of oesophageal pressure waves were examined before, and 7.5, 15, 30 and 60 min after either placebo or sildenafil. In both healthy subjects and patients with nutcracker oesophagus, sildenafil decreased resting LOS pressure and the amplitude of peristaltic pressure waves at 3, 8 and 13 cm above LOS. Sildenafil also prolonged the duration of LOS relaxation. It had no effect on the velocity of peristalsis or the amplitude of peristaltic pressure waves 18 cm above LOS. Sildenafil may be considered as an alternative treatment in nutcracker oesophagus although there are several limitations to be overcome.

Efficacy of the glucagon‐like peptide‐1 agonist exenatide in the treatment of short bowel syndrome

Background  Short bowel syndrome (SBS) is a serious clinical disorder characterized by diarrhea and nutritional deprivation. Glucagon‐like peptide‐1 (GLP‐1) is a key hormone, produced by L‐cells in the ileum, that regulates proximal gut transit. When extensive ileal resection occurrs, as in SBS, GLP‐1 levels may be deficient. In this study, we test whether the use of GLP‐1 agonist exenatide can improve the nutritional state and intestinal symptoms of patients with SBS.

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.

Short-term electrical stimulation of the lower esophageal sphincter increases sphincter pressure in patients with gastroesophageal reflux disease

Background  Electrical stimulation (ES) of the lower esophageal sphincter (LES) increases resting LES pressure (LESP) in animal models. Our aims were to evaluate the safety of such stimulation in humans, and test the hypothesis that ES increases resting LESP in patients with gastroesophageal reflux disease (GERD).

Redefining the role of lymphocytes in gastroesophageal reflux disease and eosinophilic esophagitis

Eosinophilic esophagitis (EoE) and reflux esophagitis (RE) overlap clinically and histologically. RE is characterized by epithelial infiltration with small numbers of neutrophils and eosinophils, EoE by a prominent eosinophilic infiltrate. Lymphocytic esophagitis (LE), a new entity characterized by peripapillary lymphocytosis, questions the role lymphocytes play in esophageal inflammation. We test the hypothesis that lymphocyte infiltration in RE differs from EoE. One blinded pathologist read esophageal biopsies from 39 RE and 39 EoE patients. Both groups demonstrated significant numbers of lymphocytes (RE 22.7 +/- 2.2/HPF, EoE 19.8 +/- 1.8/HPF). Eosinophils/HPF in RE and EoE were 2.8 +/- 0.7 and 74.9 +/- 8.2, respectively (P < 0.001). Neutrophils were uncommon in RE (0.26 +/- 0.16/HPF) and EoE (0.09 +/- 0.04; P = 0.07). Eight of the 39 RE specimens had >or=50 lymphocytes in >or=1 HPF. Two were consistent with LE. There was an inverse correlation between numbers of eosinophils and lymphocytes in EoE (R = -0.47; P = 0.002), and no correlation between them in RE (R = 0.18; P = 0.36). The patients with EoE who used antireflux medications had fewer lymphocytes (16.3 +/- 1.3 vs 22.2 +/- 2.3/HPF; P = 0.030) and eosinophils (55.6 +/- 5.2 vs 76.0 +/- 8.7/HPF; P = 0.042) than those who did not. The pathological role of lymphocytes in RE and EoE may be underestimated. Our observation that 5% of the RE specimens meet histopathological criteria for LE potentially blurs the line between these entities. The observation that eosinophil counts are lower in EoE when antireflux meds are used supports the notion that reflux plays a role in the clinical expression of EoE.

Effects of phosphodiesterase inhibitors on oesophageal neuromuscular functions

Abstract  The cyclic nucleotides adenosine 3′,5′‐cyclic monophosphate (cAMP) and guanosine 3′,5′‐cyclic monophosphate (cGMP) mediate the inhibitory effects of vasoactive intestinal polypeptide and nitric oxide on oesophageal smooth muscle. Phosphodiesterases (PDE) terminate their actions. We hypothesized that PDE inhibitors alter nerve‐induced responses of oesophageal and lower oesophageal sphincter (LES) smooth muscle. An electrical field known to activate intrinsic oesophageal nerves was used to stimulate transverse muscle strips from the opossum oesophagus. This produced a contractile off‐response from circular oesophageal muscle and a biphasic relaxation of the LES – an initial rapid relaxation (R1) and a slower sustained relaxation (R2). The effects on LES and oesophageal muscle of zaprinast (type V), zardaverine (type III/IV) and theophylline (non‐specific) PDE inhibitors were explored. All three PDE inhibitors decreased LES tone and attenuated the off‐response. Zaprinast and theophylline increased the latency of the off‐response. Zaprinast prolonged R1, and slowed its recovery. It also increased the percentage relaxation of the second R2. Zardaverine increased the percentage relaxation of R2. Theophylline slowed the recovery of R2. PDEs play a role in maintaining LES tone and its recovery after LES relaxation. They may also modulate oesophageal motor activity.