SEARCH

SEARCH BY CITATION

Keywords:

  • absent peristalsis;
  • high-resolution manometry;
  • impedance monitoring;
  • ineffective esophageal motility;
  • weak peristalsis

Abstract

  1. Top of page
  2. Abstract
  3. Definitions and Terms
  4. Epidemiology
  5. Pathogenesis and Pathophysiology
  6. Clinical Presentation
  7. Investigations
  8. Treatment
  9. Author Contributions
  10. Conflict of Interests
  11. References

Background  Weak and absent esophageal peristalsis are frequently encountered esophageal motility disorders, which may be associated with dysphagia and which may contribute to gastroesophageal reflux disease. Recently, rapid developments in the diagnostic armamentarium have taken place, in particular, in high-resolution manometry with or without concurrent intraluminal impedance monitoring.

Purpose  This article aims to review the current insights in the terminology, pathology, pathophysiology, clinical manifestations, diagnostic work-up,and management of weak and absent peristalsis.

Motor abnormalities of the esophagus that fit the category ‘weak and absent peristalsis’ are probably the least studied manifestations of esophageal dysfunction, likely because of the apparent lack of therapeutic options. It is important to recognize that the manometric diagnosis of esophageal hypomotility does not necessarily imply abnormal esophageal transit or presence of symptoms, including dysphagia.

Definitions and Terms

  1. Top of page
  2. Abstract
  3. Definitions and Terms
  4. Epidemiology
  5. Pathogenesis and Pathophysiology
  6. Clinical Presentation
  7. Investigations
  8. Treatment
  9. Author Contributions
  10. Conflict of Interests
  11. References

Until 1997, the term ‘nonspecific esophageal motor abnormalities’ was generally used by physiologists to denote any dysmotility pattern that was not achalasia, spasm, nutcracker or LES dysfunction. Then, Leite and coworkers published their finding that ‘ineffective esophageal motility’ (IEM) was the primary finding in patients with nonspecific esophageal motility disorder.1 In 2001, this was incorporated into Spechler and Castell’s2 classification of esophageal motor disorders, based on conventional manometry. In their classification, IEM was defined as distal-esophageal hypocontractility in at least 30% of wet swallows, characterized either as low-amplitude peristaltic waves (<30 mmHg), low-amplitude simultaneous waves (<30 mmHg) or peristaltic waves that are not propagated to the distal-esophagus, or absent peristalsis. The 30-mmHg criterion was derived from the observation that amplitudes <30 mmHg were frequently associated with bolus escape and incomplete bolus clearance.3

High-resolution manometry (HRM), with or without concurrent intraluminal impedance monitoring, allows a more complete definition of peristalsis. In the recently developed Chicago classification, frequent failed peristalsis (>30% of wet swallows) is separated from weak peristalsis (defined as breaks in the 20-mmHg isobaric contour). Weak peristalsis with large defects is judged to be present when breaks >5 cm are present in >20% of swallows (Fig. 1). Weak peristalsis with small defects is present when breaks of 2–5 cm in length are present in >30% of swallows.4 This classification of manometric abnormalities as abnormal is also based on the likelihood that such defects are associated with esophageal dysfunction (i.e. bolus escape); however, the clinical relevance of such observations remains uncertain. Indeed, it is likely that several abnormal swallows in series are required before symptoms are experienced.5

image

Figure 1.  Examples of high-resolution manometry showing weak peristalsis with small (2–5 cm) (A) and large (>5 cm) (B) breaks in the 20-mmHg isobaric contour. Reproduced with permission from Roman et al. Am J Gastroenterol 2011;106:349–356.

Download figure to PowerPoint

Epidemiology

  1. Top of page
  2. Abstract
  3. Definitions and Terms
  4. Epidemiology
  5. Pathogenesis and Pathophysiology
  6. Clinical Presentation
  7. Investigations
  8. Treatment
  9. Author Contributions
  10. Conflict of Interests
  11. References

Formally, normal values for esophageal manometry should be population-specific and stratified by age and gender such that, by definition, 5% have hypotensive contractions in every group. This quality of data does not exist. Normal values for conventional manometry are based on observations in 95 healthy subjects with a mean age of 43 years (range 22–79 years),6 whereas the two HRM studies upon which the cutoff values for peristaltic breaks were based included only volunteers under the age of 50.4,7 Data gathered with conventional manometry suggest that the amplitude of esophageal contractions is higher in men than women, rises with increasing age and is higher in Afro-Caribbean than Hispanic and Caucasian populations.6,8 This variation between demographic and racial groups may be due to specific effects of age, gender and race, or common factors such as increased outflow resistance caused by central obesity. What is beyond doubt is that esophageal hypocontractility (weak, absent or failed peristalsis) is the most prevalent finding in clinical series. In our own experience, IEM with or without hypotensive LES was found in 58% of 2610 patients referred for (conventional) manometry. In a series of 350 consecutive patients who underwent manometry for various indications IEM was found in 20.2%.9 IEM was observed in 27–32% of patients presenting with non-obstructive dysphagia without GERD.10,11 Hypocontractility is also the most prevalent esophageal motor disorder in GERD, found in 21–38% of patients in large series, and its presence is associated with the severity of acid exposure and reflux symptoms.12,13 Similarly, in a group of patients with respiratory symptoms associated with reflux, IEM was found in 53% of asthmatics, 41% of chronic coughers and 31% of those with laryngitis.14

Pathogenesis and Pathophysiology

  1. Top of page
  2. Abstract
  3. Definitions and Terms
  4. Epidemiology
  5. Pathogenesis and Pathophysiology
  6. Clinical Presentation
  7. Investigations
  8. Treatment
  9. Author Contributions
  10. Conflict of Interests
  11. References

In most cases of weak or absent peristalsis identified in the motility lab the pathogenesis of the motility disorder will remain unclear. Autopsy studies of the pathology underlying this disordered function are lacking.

The exceptions to this rule are scleroderma and related connective tissue disorders, in which esophageal pathology has been studied extensively. There are three stages in the development of esophageal involvement in scleroderma: neuropathy, myopathy, and fibrosis.15 The neuronal abnormalities in the first stage are thought to be the consequence of arteriolar changes in the vasa nervorum. In the second stage, ischemia leads to focal degeneration and atrophy of the muscle layers. Finally, the muscle tissue is replaced by fibrosis, and collagen is deposited. These changes lead to severely disturbed esophageal motility, in particular in the smooth-muscle segment. In advanced disease manometry shows absent peristalsis, with only simultaneous pressure waves in the mid- and distal-esophageal body, and low LES pressure. This combination of abnormalities leads to increased gastroesophageal reflux and impaired esophageal clearance, in particular during the night. Consequently, esophagitis and its complications (ulcer, stenosis and Barrett’s esophagus) are frequently observed in scleroderma.

Knowledge about the mechanisms underlying esophageal hypomotility associated with GERD is accumulating. In cats with experimentally induced esophagitis, inflammatory mediators, such as interleukin-6 and platelet activating factor, were found to reduce acetylcholine release from excitatory myenteric neurons.16 Similarly, the mucosa of human patients with reflux esophagitis produces significantly greater amounts of cytokines than that of healthy controls.17 However, it is uncertain whether IEM associated with GERD is always the consequence of inflammation. It is also possible that it is a primary motor disorder leading to GERD.18 Whereas, animal studies suggest that acute esophagitis-associated esophageal hypomotility can disappear after healing, studies in humans with chronic erosive GERD have shown that healing of esophagitis, either medically or surgically, is not associated with complete recovery of esophageal dysmotility.19,20

Finally, IEM can also be observed in patients without any evidence of GERD in present or past. The pathogenesis of this idiopathic disorder is almost unknown, although Kim and coworkers21 have provided initial evidence that an imbalance between the excitatory and inhibitory innervation of the esophagus, reflected in the ratio between choline acetyltransferase (ChAT) and nitric oxide synthase (nNOS) expressed in the esophageal muscle wall, may be present in IEM patients.

Clinical Presentation

  1. Top of page
  2. Abstract
  3. Definitions and Terms
  4. Epidemiology
  5. Pathogenesis and Pathophysiology
  6. Clinical Presentation
  7. Investigations
  8. Treatment
  9. Author Contributions
  10. Conflict of Interests
  11. References

Esophageal symptoms in impaired esophageal peristalsis include dysphagia, odynophagia, heartburn and regurgitation. However, the correlation between the severity of the manometric findings and the symptoms is extremely poor. Even in patients with complete absence of peristalsis, as is often the case in scleroderma, symptoms may be absent. On the other end of the spectrum, one can find patients who complain of severe dysphagia but who have completely normal esophageal peristalsis, LES function, and bolus transit on barium studies.

Investigations

  1. Top of page
  2. Abstract
  3. Definitions and Terms
  4. Epidemiology
  5. Pathogenesis and Pathophysiology
  6. Clinical Presentation
  7. Investigations
  8. Treatment
  9. Author Contributions
  10. Conflict of Interests
  11. References

Endoscopic examination of the esophagus is not a valuable tool to diagnose esophageal motility; endoscopy should always be carried out to exclude ulceration, stenosis, and neoplastic lesions before the patient is referred for evaluation of esophageal function. The good old barium esophagogram, still is a useful technique in the work-up of patients with a suspected esophageal motility disorder. It will detect obstructive lesions, esophageal dilation, and hiatus hernia at least as well as endoscopy. In addition, and most importantly, the barium esophagogram provides information about esophageal transit. For this purpose, not only barium suspension should be used, but swallowing a solid bolus, such as a marshmallow or a piece of bread, should be part of the examination. Scintigraphy does not provide structural information but is the only technique that quantifies esophageal transit.

Manometry is often considered to be the gold standard, being able to detect subtle impairment of esophageal peristalsis. The most characteristic findings in scleroderma, low-amplitude simultaneous waves, can also be observed in other connective tissue diseases and in diabetes, amyloidosis, myxedema, multiple sclerosis, chronic idiopathic intestinal pseudoobstruction, and in severe end-stage GERD without scleroderma.

Whether conventional or high-resolution manometry is used, care must be taken to avoid circumstances that can lead to a spurious diagnosis of IEM. Examples of these are the use of drugs that inhibit esophageal contractions (anticholinergic agents and calcium channel blockers), failure to have an appropriate time interval between swallows, and inclusion of dry swallows. Additionally, depending on the examination position, the appropriate normal values must be applied because contractile vigor decreases on moving from the supine to the upright position.22

The combination of esophageal manometry and intraluminal impedance measurement allows assessment of the functional impact of ineffective esophageal contractions. In a study of 350 patients, it was found that one-third of patients with a manometric diagnosis of IEM had ‘effective’ transit for both liquid and viscous swallows.9 Similar findings were reported by others, suggesting that the definition of weak peristalsis should include functional correlates.4,23 High-resolution manometry, ideally combined with fluoroscopy or impedance, clarifies the relationship between dysmotility and bolus retention.4,24–26 The introduction of solid swallows or a test meal to manometric studies may further increase sensitivity to dysfunction associated with symptoms in ‘functional’ dysphagia25,26 and mucosal disease in GERD.27

Treatment

  1. Top of page
  2. Abstract
  3. Definitions and Terms
  4. Epidemiology
  5. Pathogenesis and Pathophysiology
  6. Clinical Presentation
  7. Investigations
  8. Treatment
  9. Author Contributions
  10. Conflict of Interests
  11. References

Specific treatment is clearly desirable for patients with evidence of symptoms related to hypotensive dysmotility or reflux; however, the options are limited because there is no pharmacologic intervention that reliably restores smooth-muscle contractility and esophageal function. Thus, dietary and lifestyle advice together with effective control of acid reflux, if present, are the mainstays of clinical management.

Dietary and lifestyle management

A ‘common sense’ approach can reduce the risk of symptomatic bolus retention. Patients should favor liquid and semi-solid nutrition over solids, consume meals in the upright position, chew well and take plenty of fluids as these measures all promote esophageal clearance.28 Indeed, it appears that the ‘pharyngeal pump’ together with gravity and hydrostatic forces can move not only liquids but also most solid food through the esophagus without the need for active esophageal contraction.28,29 Many experts also recommend liberal use of carbonated beverages, because this may prevent as well as resolve bolus retention.30,31

Treatment of gastroesophageal reflux disease associated with hypotensive dysmotility

Patients with hypotensive motility with weak lower esophageal sphincter function often experience severe symptoms and complications of GERD because poor clearance leads to prolonged acid exposure, particularly at night.15 These problems are marked in patients with systemic sclerosis in whom the combination of poor motility and poor salivation impacts on both volume and chemical (i.e. acid) clearance.32 Dietary and lifestyle measures may be helpful, although these are rarely sufficient in severe GERD. A systematic review identified several such interventions that reduce esophageal acid exposure,33 some of which may be of particular benefit in patients with hypotensive dysmotility. These included (i) weight loss, (ii) keeping the upper body in an elevated position after a meal, (iii) lying down in the right lateral position, (iv) not smoking, (v) not consuming alcohol, (vi) reduction of meal size, and (vii) reduction in calorie load. Reduction in fat intake may be of additional value as this has high caloric density and also appears to sensitize the esophagus to acid reflux events.34 In addition, chewing gum for half an hour after meals may be helpful,35 as this stimulates salivation and swallowing, improving both volume and chemical clearance.

High-dose acid suppression taken twice a day is often required to suppress gastric acid, heal esophagitis and provide effective symptom relief in patients with severe hypotensive disease.36 Some patients benefit also from alginate preparations taken after the meal that suppress both acid and non-acid reflux events by forming a viscous layer over the gastric contents.37 The addition of ranitidine to suppress basal, nocturnal acid secretion appears to be helpful in individual patients but was not effective in a randomized controlled trial in 14 patients with systemic sclerosis.38

Prokinetics

Procholinergic agents  Medications that increase the concentration of acetylcholine in the synaptic cleft or directly stimulate muscarinic receptors promote smooth-muscle contractility. Bethanechol, a direct-acting muscarinic receptor agonist, has been shown in healthy volunteers and patients with hypotensive esophageal dysmotility to increase peristaltic amplitude in the distal-esophagus.39 Using combined multichannel intraluminal impedance- manometry in seven patients with severe IEM, Agrawal and coworkers39 demonstrated that a single oral dose of 50 mg bethanechol increased both contractile pressure and bolus clearance. Similar effects on contractile pressure were reported by Blonski and coworkers40 for a range of oral procholinergic agents, including bethanechol (25 mg), pyridostygmine (60 mg), and buspirone (20 mg), with pyridostigmine also promoting bolus transport. No trials demonstrating clinical efficacy have been published. Nevertheless, some experts report benefit of these medications in individual patients, although side-effects such as excessive salivation and diarrhea may limit use.

Dopamine antagonists  Domperidone is a D2 receptor antagonist that promotes gastrointestinal motility by antagonizing the inhibitory effects of dopamine on postsynaptic cholinergic neurons in the myenteric plexus.41 Metoclopramide augments this peripheral effect with procholinergic properties and also has central anti-emetic actions at the chemoreceptor trigger zone.42 These medications increase LES pressure, accelerate gastric emptying and improve symptoms in patients with GERD and also diabetic gastroparesis.43,44 Effects on esophageal peristalsis and clearance are less well established. No effect of 20 mg domperidone on esophageal emptying was found on scintigraphy in 12 patients with diabetic autonomic neuropathy and esophageal dysfunction.45 In contrast, a significant improvement in clearance was reported after administration of 10 mg intravenous metoclopramide in 14 patients with systemic sclerosis.46

Motilin agonists  Erythromycin and other macrolide antibiotics have pronounced prokinetic side-effects that are utilized by physicians treating patients with severe gastrointestinal dysmotility such as gastroparesis and pseudo-obstruction.47 This effect is mediated by motilin receptors that play a key role in the initiation of phase III migrating motor complex (MMC), inter-digestive ‘housekeeping’ contractions that sweep the stomach, and bowel clear of undigested material and bacterial overgrowth.47 Chrysos and coworkers48 showed that intravenous erythromycin (200 mg i.v. bolus) increased contractile vigor and LES pressure in 15 GERD patients, and in a 2-week clinical study Chang and coworkers49 reported that erythromycin (250 mg tid) significantly shortened esophageal and gastric transit and improved glycemic control in diabetic patients. Although these findings are impressive, the clinical use of erythromycin is limited by tachyphylaxis and side-effects including dyspepsia and diarrhea. New motilin agonists that may be better tolerated are in development. However, one recent example, ABT-229, had no effect on LES function, esophageal motility ,and reflux, in GERD patients.50

Serotonin agonists  Cisapride and mosapride are prokinetic agents with mixed 5-HT4 agonist/5-HT3 antagonist action. Tegaserod, prucalopride, and other selective 5HT4 agonists have similar actions.42 Serotonin is released from enterochromaffin cells on mechanical stimulation and 5-HT4 receptors facilitate acetylcholine release in the myenteric plexus that triggers peristaltic contraction and clearance.51 Thus, in contrast to muscarinic antagonists and motilin agonists, 5-HT4 agonists promote normal gastrointestinal transit rather than inducing powerful but unphysiological contractions. These agents have prokinetic effects throughout the gastrointestinal tract and proven clinical efficacy in various conditions characterized by slow-transit, including GERD, diabetic gastroparesis and constipation.52 Studies have demonstrated that cisapride and mosapride increase LES pressure, promote esophageal clearance, and reduce acid exposure in health and GERD patients.53,54 However, the mechanism of this action was not evident on conventional motility studies.53–55 Soon after the introduction of high-resolution manometry with esophageal pressure topography Staiano and Clouse56 observed that cisapride enhanced contraction in the proximal smooth-muscle segment of the esophageal body. The functional significance of this effect was confirmed by combined HRM-videofluoroscopy that showed tegaserod improved co-ordination between contractile segments, leading to more effective solid-bolus transport (Fig. 2).57 Cisapride and tegaserod have been withdrawn due to rare, but occasionally life-threatening, side-effects; however, new 5-HT4 agonists are in the pipeline or are in the market approved for other indications.52 Clinical trials in GERD are in progress and, hopefully, studies in symptomatic, hypotensive esophageal motility will follow.

image

Figure 2.  Concurrent fluoroscopy and high-resolution manometry (HRM) reveals the functional importance of co-ordination between the proximal and mid-distal esophageal contractions for solid-bolus transport and the prokinetic effects of the 5-HT4 agonist tegaserod. (A) Patient no. 6: placebo treatment. HRM shows a break in the contractile front (>3 cm) at the proximal transition zone, the peristaltic contraction is otherwise preserved. Concurrent fluoroscopy reveals solid-bolus escape at the level of the proximal transition zone (note the corresponding pressure rise at the level of bolus impaction). In contrast, the liquid barium ingested with the marshmallow was propelled into the distal-esophagus and most was transported into the stomach. (B) Patient no. 6: tegaserod treatment. The pressure trough at the proximal transition zone is less pronounced on the HRM plot, the peristaltic contraction in the proximal esophagus is well co-ordinated with the mid- and distal-esophagus. Concurrent fluoroscopy reveals effective solid and liquid bolus transport (note the pressure rise as the bolus passes through the gastro-esophageal junction into the stomach). Adapted with permission from Fox et al. Aliment Pharmacol Ther 2006; 24: 1017–1027.

Download figure to PowerPoint

Surgery

In patients with severe GERD, impaired peristalsis, impaired esophageal clearance, and dysphagia are common. The dysphagia can be not only due to the hypotensive dysmotility3, but also to mechanical outflow obstruction at the esophagogastric junction in the presence of hiatus hernia.58 In some cases anti-reflux surgery may not only improve reflux symptoms but also reduce dysphagia.20,59,60 This may be due to improvement of esophageal motility and visceral hypersensitivity with normalization of acid exposure or due to reduction of the hiatus hernia. However, the literature on the effect of fundoplication on esophageal motility and the relationship between preoperative motility and outcome of surgery should be interpreted with caution. Flaws in the design of these studies and manometric techniques employed should be taken into account. Some of these studies concluded that hypotensive dysmotility is not a contra-indication to surgical management of GERD, many experts in the field hold the opinion that fundoplication should not be carried out in patients with severe IEM.

Author Contributions

  1. Top of page
  2. Abstract
  3. Definitions and Terms
  4. Epidemiology
  5. Pathogenesis and Pathophysiology
  6. Clinical Presentation
  7. Investigations
  8. Treatment
  9. Author Contributions
  10. Conflict of Interests
  11. References

AS and MF performed the literature search underlying this article, analyzed the data and wrote the article.

References

  1. Top of page
  2. Abstract
  3. Definitions and Terms
  4. Epidemiology
  5. Pathogenesis and Pathophysiology
  6. Clinical Presentation
  7. Investigations
  8. Treatment
  9. Author Contributions
  10. Conflict of Interests
  11. References
  • 1
    Leite LP, Johnston BT, Barrett J, Castell JA, Castell DO. Ineffective esophageal motility (IEM): the primary finding in patients with nonspecific esophageal motility disorder. Dig Dis Sci 1997; 42: 185965.
  • 2
    Spechler SJ, Castell DO. Classification of oesophageal motility abnormalities. Gut 2001; 49: 14551.
  • 3
    Kahrilas PJ, Dodds WJ, Hogan WJ. Effect of peristaltic dysfunction on esophageal volume clearance. Gastroenterology 1988; 94: 7380.
  • 4
    Roman S, Lin Z, Kwiatek MA, Pandolfino JE, Kahrilas PJ. Weak peristalsis in esophageal pressure topography: classification and association with Dysphagia. Am J Gastroenterol 2011; 106: 34956.
  • 5
    Fox M, Bredenoord AJ. High resolution manometry: moving from research into clinical practice. Gut 2008; 57: 40523.
  • 6
    Richter JE, Wu WC, Johns DN et al. Esophageal manometry in 95 healthy adult volunteers. Variability of pressures with age and frequency of “abnormal” contractions. Dig Dis Sci 1987; 32: 58392.
  • 7
    Ghosh SK, Pandolfino JE, Zhang Q, Jarosz A, Shah N, Kahrilas PJ. Quantifying esophageal peristalsis with high-resolution manometry: a study of 75 asymptomatic volunteers. Am J Physiol Gastrointest Liver Physiol 2006; 290: G98897.
  • 8
    Vega KJ, Langford-Legg T, Jamal MM. Ethnic variation in lower oesophageal sphincter pressure and length. Aliment Pharmacol Ther 2008; 28: 6559.
  • 9
    Tutuian R, Castell DO. Combined multichannel intraluminal impedance and manometry clarifies esophageal function abnormalities: study in 350 patients. Am J Gastroenterol 2004; 99: 10119.
    Direct Link:
  • 10
    Conchillo JM, Nguyen NQ, Samsom M, Holloway RH, Smout AJ. Multichannel intraluminal impedance monitoring in the evaluation of patients with non-obstructive Dysphagia. Am J Gastroenterol 2005; 100: 262432.
    Direct Link:
  • 11
    Dekel R, Pearson T, Wendel C, De Garmo P, Fennerty MB, Fass R. Assessment of oesophageal motor function in patients with dysphagia or chest pain – the Clinical Outcomes Research Initiative experience. Aliment Pharmacol Ther 2003; 18: 10839.
  • 12
    Diener U, Patti MG, Molena D, Fisichella PM, Way LW. Esophageal dysmotility and gastroesophageal reflux disease. J Gastrointest Surg 2001; 5: 2605.
  • 13
    Lee J, Anggiansah A, Anggiansah R, Young A, Wong T, Fox M. Effects of age on the gastroesophageal junction, esophageal motility, and reflux disease. Clin Gastroenterol Hepatol 2007; 5: 13928.
  • 14
    Fouad YM, Katz PO, Hatlebakk JG, Castell DO. Ineffective esophageal motility: the most common motility abnormality in patients with GERD-associated respiratory symptoms. Am J Gastroenterol 1999; 94: 14647.
    Direct Link:
  • 15
    Sallam H, McNearney TA, Chen JD. Systematic review: pathophysiology and management of gastrointestinal dysmotility in systemic sclerosis (scleroderma). Aliment Pharmacol Ther 2006; 23: 691712.
  • 16
    Cheng L, Cao W, Fiocchi C, Behar J, Biancani P, Harnett KM. Platelet-activating factor and prostaglandin E2 impair esophageal ACh release in experimental esophagitis. Am J Physiol Gastrointest Liver Physiol 2005; 289: G41828.
  • 17
    Rieder F, Cheng L, Harnett KM et al. Gastroesophageal reflux disease-associated esophagitis induces endogenous cytokine production leading to motor abnormalities. Gastroenterology 2007; 132: 15465.
  • 18
    Fox M, Forgacs I. Gastro-oesophageal reflux disease. BMJ 2006; 332: 8893.
  • 19
    Timmer R, Breumelhof R, Nadorp JH, Smout AJ. Oesophageal motility and gastro-oesophageal reflux before and after healing of reflux oesophagitis. A study using 24 hour ambulatory pH and pressure monitoring. Gut 1994; 35: 151922.
  • 20
    Fibbe C, Layer P, Keller J, Strate U, Emmermann A, Zornig C. Esophageal motility in reflux disease before and after fundoplication: a prospective, randomized, clinical, and manometric study. Gastroenterology 2001; 121: 514.
  • 21
    Kim HS, Park H, Lim JH et al. Morphometric evaluation of oesophageal wall in patients with nutcracker oesophagus and ineffective oesophageal motility. Neurogastroenterol Motil 2008; 20: 86976.
  • 22
    Sweis R, Anggiansah A, Wong T, Kaufman E, Obrecht S, Fox M. Normative values and inter-observer agreement for liquid and solid bolus swallows in upright and supine positions as assessed by esophageal high-resolution manometry. Neurogastroenterol Motil 2011; 23: 509e198.
  • 23
    Nguyen NQ, Tippett M, Smout AJ, Holloway RH. Relationship between pressure wave amplitude and esophageal bolus clearance assessed by combined manometry and multichannel intraluminal impedance measurement. Am J Gastroenterol 2006; 101: 247684.
    Direct Link:
  • 24
    Bulsiewicz WJ, Kahrilas PJ, Kwiatek MA, Ghosh SK, Meek A, Pandolfino JE. Esophageal pressure topography criteria indicative of incomplete bolus clearance: a study using high-resolution impedance manometry. Am J Gastroenterol 2009; 104: 27218.
  • 25
    Fox M, Hebbard G, Janiak P et al. High-resolution manometry predicts the success of oesophageal bolus transport and identifies clinically important abnormalities not detected by conventional manometry. Neurogastroenterol Motil 2004; 16: 53342.
  • 26
    Sweis R, Anggiansah A, Wong T, Fox M. Inclusion of solid swallows and a test meal increase the clinical utility of High Resolution Manometry in patients with dysphagia. Gastroenterology 2010; 138: S 600 (T1889).
  • 27
    Daum C, Sweis R, Kaufman E et al. Failure to respond to physiologic challenge characterizes esophageal motility in erosive gastro-esophageal reflux disease. Neurogastroenterol Motil 2011; 23: 517e200.
  • 28
    Pouderoux P, Shi G, Tatum RP, Kahrilas PJ. Esophageal solid bolus transit: studies using concurrent videofluoroscopy and manometry. Am J Gastroenterol 1999; 94: 145763.
    Direct Link:
  • 29
    Simren M, Silny J, Holloway R, Tack J, Janssens J, Sifrim D. Relevance of ineffective oesophageal motility during oesophageal acid clearance. Gut 2003; 52: 78490.
  • 30
    Holdaway A, Davis M. Palliation in cancer of the oesophagus – what passes down an oesophageal stent? J Hum Nutr Dietet 2003; 16: 36570.
  • 31
    Mohammed SH, Hegedus V. Dislodgement of impacted oesophageal foreign bodies with carbonated beverages. Clin Radiol 1986; 37: 58992.
  • 32
    Sjogren RW. Gastrointestinal motility disorders in scleroderma. Arthritis Rheum 1994; 37: 126582.
  • 33
    Kaltenbach T, Crockett S, Gerson LB. Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach. Arch Intern Med 2006; 166: 96571.
  • 34
    Fox M, Barr C, Nolan S, Lomer M, Anggiansah A, Wong T. The effects of dietary fat and calorie density on esophageal acid exposure and reflux symptoms. Clin Gastroenterol Hepatol 2007; 5: 43944.
  • 35
    Moazzez R, Bartlett D, Anggiansah A. The effect of chewing sugar-free gum on gastro-esophageal reflux. J Dent Res 2005; 84: 10625.
  • 36
    Hendel L, Hage E, Hendel J, Stentoft P. Omeprazole in the long-term treatment of severe gastro-oesophageal reflux disease in patients with systemic sclerosis. Aliment Pharmacol Ther 1992; 6: 56577.
  • 37
    Buts JP, Barudi C, Otte JB. Double-blind controlled study on the efficacy of sodium alginate (Gaviscon) in reducing gastroesophageal reflux assessed by 24 h continuous pH monitoring in infants and children. Eur J Pediatr 1987; 146: 1568.
  • 38
    Janiak P, Thumshirn M, Menne D et al. Clinical trial: the effects of adding ranitidine at night to twice daily omeprazole therapy on nocturnal acid breakthrough and acid reflux in patients with systemic sclerosis – a randomized controlled, cross-over trial. Aliment Pharmacol Ther 2007; 26: 125965.
  • 39
    Agrawal A, Hila A, Tutuian R, Mainie I, Castell DO. Bethanechol improves smooth muscle function in patients with severe ineffective esophageal motility. J Clin Gastroenterol 2007; 41: 36670.
  • 40
    Blonski W, Vela MF, Freeman J, Sharma N, Castell DO. The effect of oral buspirone, pyridostigmine, and bethanechol on esophageal function evaluated with combined multichannel esophageal impedance-manometry in healthy volunteers. J Clin Gastroenterol 2009; 43: 25360.
  • 41
    Takahashi T, Kurosawa S, Wiley JW, Owyang C. Mechanism for the gastrokinetic action of domperidone. In vitro studies in guinea pigs. Gastroenterology 1991; 101: 70310.
  • 42
    Tonini M, Candura SM, Messori E, Rizzi CA. Therapeutic potential of drugs with mixed 5-HT4 agonist/5-HT3 antagonist action in the control of emesis. Pharmacol Res 1995; 31: 25760.
  • 43
    Maddern GJ, Kiroff GK, Leppard PI, Jamieson GG. Domperidone, metoclopramide, and placebo. All give symptomatic improvement in gastroesophageal reflux. J Clin Gastroenterol 1986; 8: 13540.
  • 44
    Sturm A, Holtmann G, Goebell H, Gerken G. Prokinetics in patients with gastroparesis: a systematic analysis. Digestion 1999; 60: 4227.
  • 45
    Maddern GJ, Horowitz M, Jamieson GG. The effect of domperidone on oesophageal emptying in diabetic autonomic neuropathy. Br J Clin Pharmacol 1985; 19: 4414.
  • 46
    Drane WE, Karvelis K, Johnson DA, Curran JJ, Silverman ED. Scintigraphic detection of metoclopramide esophageal stimulation in progressive systemic sclerosis. J Nucl Med 1987; 28: 8105.
  • 47
    Quigley EM. Gastric and small intestinal motility in health and disease. Gastroenterol Clin North Am 1996; 25: 11345.
  • 48
    Chrysos E, Tzovaras G, Epanomeritakis E et al. Erythromycin enhances oesophageal motility in patients with gastro-oesophageal reflux. ANZ J Surg 2001; 71: 98102.
  • 49
    Chang CT, Shiau YC, Lin CC, Li TC, Lee CC, Kao CH. Improvement of esophageal and gastric motility after 2-week treatment of oral erythromycin in patients with non-insulin-dependent diabetes mellitus. J Diabetes Complications 2003; 17: 1414.
  • 50
    Van Herwaarden MA, Samsom M, Van Nispen CH, Verlinden M, Smout AJ. The effect of motilin agonist ABT-229 on gastro-oesophageal reflux, oesophageal motility and lower oesophageal sphincter characteristics in GERD patients. Aliment Pharmacol Ther 2000; 14: 45362.
  • 51
    Gershon MD. Review article: serotonin receptors and transporters – roles in normal and abnormal gastrointestinal motility. Aliment Pharmacol Ther 2004; 20(Suppl. 7): 314.
  • 52
    Sanger GJ. Translating 5-HT receptor pharmacology. Neurogastroenterol Motil 2009; 21: 12358.
  • 53
    Smout AJ, Bogaard JW, Grade AC, ten Thije OJ, Akkermans LM, Wittebol P. Effects of cisapride, a new gastrointestinal prokinetic substance, on interdigestive and postprandial motor activity of the distal oesophagus in man. Gut 1985; 26: 24651.
  • 54
    Ruth M, Finizia C, Cange L, Lundell L. The effect of mosapride on oesophageal motor function and acid reflux in patients with gastro-oesophageal reflux disease. Eur J Gastroenterol Hepatol 2003; 15: 111521.
  • 55
    Koshino K, Adachi K, Furuta K et al. Effects of mosapride on esophageal functions and gastroesophageal reflux. J Gastroenterol Hepatol 2010; 25: 106671.
  • 56
    Staiano A, Clouse RE. The effects of cisapride on the topography of oesophageal peristalsis. Aliment Pharmacol Ther 1996; 10: 87582.
  • 57
    Fox M, Menne D, Stutz B, Fried M, Schwizer W. The effects of tegaserod on oesophageal function and bolus transport in healthy volunteers: studies using concurrent high-resolution manometry and videofluoroscopy. Aliment Pharmacol Ther 2006; 24: 101727.
  • 58
    Pandolfino JE, Kwiatek MA, Ho K, Scherer JR, Kahrilas PJ. Unique features of esophagogastric junction pressure topography in hiatus hernia patients with dysphagia. Surgery 2010; 147: 5764.
  • 59
    Herbella FA, Tedesco P, Nipomnick I, Fisichella PM, Patti MG. Effect of partial and total laparoscopic fundoplication on esophageal body motility. Surg Endosc 2007; 21: 2858.
  • 60
    Munitiz V, Ortiz A, Martinez de Haro LF, Molina J, Parrilla P. Ineffective oesophageal motility does not affect the clinical outcome of open Nissen fundoplication. Br J Surg 2004; 91: 10104.