Diseases of the Esophagus (2015) ••, ••–•• DOI: 10.1111/dote.12367
Original article
Esophageal hypermotility: cause or effect? O. M. Crespin, R. P. Tatum, R. B. Yates, M. Sahin, K. Coskun, A. V. Martin, A. Wright, B. K. Oelschlager, C. A. Pellegrini University of Washington, Surgery, Seattle, WA, USA
Summary. Nutcracker esophagus (NE), Jackhammer esophagus (JHE), distal esophageal spasm (DES), and hypertensive lower esophageal sphincter (HTLES) are defined by esophageal manometric findings. Some patients with these esophageal motility disorders also have abnormal gastroesophageal reflux. It is unclear to what extent these patients’ symptoms are caused by the motility disorder, the acid reflux, or both. The aim of this study was to determine the effectiveness of laparoscopic Nissen fundoplication (LNF) on esophageal motility disorders, gastroesophageal reflux, and patient symptoms. Between 2007 and 2013, we performed high-resolution esophageal manometry on 3400 patients, and 221 patients were found to have a spastic esophageal motility disorder. The medical records of these patients were reviewed to determine the manometric abnormality, presence of gastroesophageal symptoms, and amount of esophageal acid exposure. In those patients that underwent LNF, we compared pre- and postoperative esophageal motility, gastroesophageal symptom severity, and esophageal acid exposure. Of the 221 patients with spastic motility disorders, 77 had NE, 2 had JHE, 30 had DES, and 112 had HTLES. The most frequently reported primary and secondary symptoms among all patients were: heartburn and/or regurgitation, 69.2%; respiratory, 39.8%; dysphagia, 35.7%; and chest pain, 22.6%. Of the 221 patients, 192 underwent 24-hour pH monitoring, and 103 demonstrated abnormal distal esophageal acid exposure. Abnormal 24-hour pH monitoring was detected in 62% of patients with heartburn and regurgitation, 49% of patients with respiratory symptoms, 36.8 % of patients with dysphagia, and 32.6% of patients with chest pain. Sixty-six of the 103 patients with abnormal 24-hour pH monitoring underwent LNF. Thirty-eight (13NE, 2JHE, 6 DES, and 17 HTLES) of these 66 patients had a minimum of 6-month postoperative follow-up that included clinical evaluation, esophageal manometry, and 24-hour pH monitoring. Postoperatively, all 38 patients had normal distal esophageal acid exposure. Of these 38 patients, symptoms resolved in 28 and improved in 10. Of six patients (one with NE, two JHE, and three with HTLES) that underwent postoperative esophageal manometry, five exhibited normal motility. Typical reflux symptoms are common among patients with esophageal hypermotility disorders. Abnormal 24-hour pH monitoring is present in the majority of patients with who report typical reflux symptoms and almost half of patients who report respiratory symptoms. Conversely, the majority of patients who report dysphagia or chest pain have normal distal esophageal acid exposure. Based on a small number of patients in this study, it also appears that motility disorders often improve after LNF. LNF is associated with resolution or improvement in reflux related symptoms and esophageal motility parameters in patients exhibiting abnormal esophageal acid exposure. This suggests that patient symptoms are due to abnormal acid exposure and not the motility disorder. KEY WORDS: distal esophageal spasm, esophageal spastic motility disorders, gastroesophageal reflux disease, hypertensive lower esophageal sphincter, laparoscopic Nissen fundoplication, nutcracker esophagus.
Address correspondence to: Roger Tatum, MD, University of Washington, Surgery, Seattle, WA 98195, USA. Email: [email protected] This study was performed at University of Washington Medical Center. The content of this study has not been published elsewhere. This study was accepted and presented as poster at Digestive Disease Week 2014. This study was reviewed and approved by the University of Washington Investigational Review Board, #46445-EA. All authors have no financial support or relationships that may pose conflict of interest. © 2015 International Society for Diseases of the Esophagus
INTRODUCTION Recent studies have demonstrated an association between gastroesophageal reflux disease (GERD) and some esophageal motility disorders. For example, GERD has been identified in patients with hypocontractile esophagus – a motility disorder characterized by a hypotensive lower esophageal sphincter (LES) and ineffective esophageal motility1–5 1
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Diseases of the Esophagus
Furthermore, in patients with hypocontractile esophagus, there appears to be a positive correlation between the degree abnormal acid exposure, the severity of the LES abnormality, and the presence of typical reflux symptoms. The link between GERD and hypermotility disorders – Nutcracker esophagus (NE), Jackhammer esophagus JHE, distal esophageal spasm (DES), and hypertensive lower esophageal sphincter (HTLES) – is less clear. Some of these patients may describe dysphagia or chest pain while some others will primarily complain of heartburn and regurgitation or a combination of all of these symptoms. To what extent the motility disorder or the acid reflux is responsible for these patients’ complaints remains controversial. Thus, the optimal treatment for patients with concomitant spastic motility disorders and GERD is not established.6–9 Therefore, the aim of this study was to evaluate symptom presentation, the presence of GERD, and the effect of antireflux surgery (laparoscopic Nissen fundoplication, LNF) in patients with esophageal hypermotility disorders of the esophagus. METHODS Between 2008 and 2012, 3400 high-resolution manometry (HRM) studies were performed at the University of Washington Medical Center in Seattle, Washington. Hypermotility disorders were diagnosed in 221 patients, who were referred for surgical evaluation. This study was reviewed and approved by the University of Washington Investigational Review Board, #46445-EA. Patient symptoms Clinical records were reviewed for primary and secondary symptoms reported by patients. Because of the retrospective nature of this review, a specific symptom scale was not used, rather merely an identification of the symptoms that drove the patient to seek evaluation, and whether or not these were the main symptom or an additional associated symptom. Respiratory symptoms included cough, hoarseness, sore throat, dyspnea, and shortness of breath. Postoperatively, patient symptoms were rated as resolved (all primary and secondary symptoms disappeared entirely), improved (reduction in severity of all primary and secondary symptoms), or unchanged (symptom severity was the same or worse compared with preoperatively, or the patient developed new symptoms). In 38 patients that underwent LNF, clinical notes were collected at a mean of 12 months (range 6–48 months) postoperatively. 24-hour pH monitoring Ambulatory 24-hour pH monitoring was performed using a dual-channel catheter. The distal channel was
positioned 5 cm above the manometrically determined LES, and the proximal channel was located 10 centimeters above the distal channel. A portable digital data logger was used to record pH fluctuations, and the patient recorded symptoms in an event diary. The information was analyzed using a Digitrapper and Synectics Software. Abnormal distal esophageal acid exposure was present when the total percent of time pH below 4 was greater than 4.5% or the De Meester score higher than 14.7. High-resolution manometry and spastic motility disorders High-resolution manometry was performed using a 32-sensor solid-state catheter and the Insight Acquisition System. Analysis was completed using BioVIEW Analysis esophageal manometry software (Sandhill Scientific, Inc., Colorado). The diagnosis of motility disorders was performed according to the Chicago classification; however, we also included the clinical entity of HTLES from previous manometric classifications using the criteria described by Salvador and colleagues.10,11
RESULTS Of 3400 high-resolution manometry procedures performed during the study period, 221 patients (132 female, mean age 58 years, range 19–91) were identified as having one of the esophageal hypercontractility disorders (77 NE, 2 JHE, 30 DES, 112 HTLES). Among these patients, 153 (69.2%) reported symptoms of heartburn or regurgitation, 88 (39.8%) reported respiratory symptoms including cough or hoarseness, 79 (35.7%) reported dysphagia, and 50 (22.6%) reported chest pain. The distribution of symptom frequency for each motility disorder is shown in Figures 1–3; for simplicity, jackhammer esophagus was included in the NE group. 24-hour pH monitoring Twenty-nine patients did not undergo 24-hour pH monitoring prior to LNF due to the presence of an epiphrenic diverticulum or large paraesophageal hernia. In 192 patients that underwent 24-hour pH monitoring, 103 (53.6%) patients had abnormal distal esophageal acid exposure. There was no difference in the frequency of abnormal 24-hour pH monitoring among the specific spastic motility disorders: NE (including 2 JHE), 57%; DES, 64%; and HTLES, 49% (p = 0.35). Abnormal 24-hour pH monitoring with an acid-reflux pattern (as opposed to a fermentation pattern which is sometimes seen in patients with achalasia) was present in 64% of patients with typical reflux symptoms and in 49% of patients who reported © 2015 International Society for Diseases of the Esophagus
Motility disorders of the esophagus
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respiratory symptoms, which was significantly higher than was observed in patients complaining primarily of dysphagia (37%) or chest pain (33%, P < 0.001 for both). Symptom correlation data was available for 171 of the patients who underwent 24-hour pH monitoring. Table 1 demonstrates that for patients with an abnormal pH study, the symptom index was much more likely to be positive (>50%) for reflux symptoms (heartburn and/or regurgitation) and dysphagia than for chest pain or respiratory symptoms.
Outcomes of laparoscopic Nissen fundoplication in patients with spastic motility Laparoscopic Nissen Fundoplication was performed in 66 of 103 (64%) of patients with abnormal 24-hour pH monitoring. Of the 37 patients that did not undergo LNF, seven patients declined the operation, seven patients were recommended to undergo gastric bypass rather than LNF due to concomitant obesity, and surgery was contraindicated in 23 patients due to comorbid medical conditions. Thirty-eight LNF patients had a minimum of 6 months of follow-up data; these included 13 NE, 2 JHE, 6 DES, and 17 HTLES. Of these, 28 (74%) patients reported symptom resolution and 10 (24%) reported symptom improvement. All of these patients demonstrated normalization of distal esophageal acid exposure on postoperative 24-hour pH monitoring (Tables 2 and 3). At a mean of 8 months (range 6 to 12 months) postoperatively, six patients underwent HRM. Figures 4 and 5 demonstrate postoperative improvement in the key esophageal manometric parameters for one patient with preoperative evidence of NE, 2 with JHE, and three patients with preoperative HTLES.
DISCUSSION
Figs 1–3 Distribution of symptom frequency among patients with motility disorders. Symptoms reported were either primary (dominant) symptoms or secondary symptoms reported in association with other symptoms (Reflux symptoms: heartburn and regurgitation; Respiratory symptoms: cough, hoarseness, sore throat, dyspnea, and shortness of breath).
Although chest pain and dysphagia are the symptoms that are commonly associated with spastic motility disorders of the esophagus,12–14 the most frequent symptoms in our patient population were heartburn and/or regurgitation followed by respiratory symptoms. In concordance with other authors, we do not believe that symptoms alone can distinguish primary motility disorders from disorders associated with
Table 1 Symptom Index in 171 patients reporting symptoms during 24-hour pH monitoring Symptom index %, median (range)
Normal acid exposure (n = 81) Patients with abnormal acid exposure (n = 90)
Reflux (heartburn/ regurgitation)
Dysphagia
Respiratory
Chest pain
21 (0–75) 78 (0–100)
17 (0–66) 50 (0–89)
7 (0–35) 34 (0–81)
5 (0–47) 10 (0–87)
© 2015 International Society for Diseases of the Esophagus
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Diseases of the Esophagus
Table 2 Results of pre- and postoperative 24-hour pH monitoring in 38 patients with spastic motility disorders. All values are reported as mean (range)
Total % time pH < 4 DeMeester score
Preoperative
Postoperative
10.6 (4.8–23.1) 28.6 (15.1–97.3)
2.03 (0.8–3.7) 5.1 (1.1–9.9)
Table 3 The effect of laparoscopic Nissen fundoplication on severity of primary and secondary symptoms reported by 38 patients with hypercontractility disorders Motility disorder
Symptom resolution
Symptom improvement
No improvement
NE (13) JHE (2) DES (6) HTLES (17) Total (38)
10 2 4 12 28
3 – 2 5 10
0 0 0 0 0
DES, distal esophageal spasm; JHE, Jackhammer esophagus; HTLES, hypertensive lower esophageal sphincter; NE, Nutcracker esophagus.
reflux (the so-called ‘secondary’ motility disorders)15,16 Our data support this: abnormal 24-hour pH monitoring was identified in the majority of patients with heartburn and/or regurgitation as well as almost half of patients with respiratory symptoms. Moreover, the majority of patients with chest pain or dysphagia did not have abnormal pH studies. Contrary to some clinicians who prefer to start treating patients with spastic motility disorders and GERD symptoms with an empiric trial of protonpump inhibitors, we believe that performance of both esophageal manometry and 24-hour pH monitoring is essential to correctly identify the causative disorder and formulate an appropriate treatment plan because it is impossible to determine based solely on symptoms whether the underlying disorder is one of motility or reflux.15–17 In our clinic, we have observed two distinct referral patterns that support this practice. In the first, patients who are referred for antireflux surgery and undergo preoperative esophageal manometry are found to have a previously undiagnosed motility abnormality. In the second, patients who are referred for further workup of a suspected or already-identified esophageal motility abnormality and undergo 24-hour pH monitoring are found to have abnormal esophageal acid exposure. In both situations, we consider that the performance of both esophageal manometry and 24-hour pH monitoring is essential in guiding treatment recommendations. The two exceptions to this practice occur in patients with either a large paraesophageal hernia or an epiphrenic diverticulum, in which case we perform esophageal manometry but not 24-hour pH monitoring. In the presence of a large paraesophageal hernia, accurate placement of the distal channel on the pH
catheter is very difficult, increasing the likelihood of invalid results. Further, paraesophageal hernia and epiphrenic diverticula are anatomic abnormalities that require operative repair to relieve obstructive symptoms; the results of 24-hour pH monitoring are unlikely to alter the recommendation for surgical repair.18,19 Finally, we routinely perform an antireflux procedure as part of these operations with good results. Hence, 29 of our patients with one of these motility disorders did not undergo pH monitoring prior to LNF. When reflux was present, we observed very good control of both esophageal acid exposure and patient symptoms with LNF. We have previously reported our initial experience in performing this procedure in patients with NE and HTLES associated with GERD.20 Since then, we have been offering this operation to that subset of patients. In this study, we report similar favorable results in six patients with DES and GERD. It is very difficult to demonstrate a cause and effect relationship between distal esophageal acid exposure
Fig. 4 Pre- and postoperative distal contractile integral (DCI) in one patient with Nutcracker esophagus (NE) and two patients with Jackhammer esophagus (JHE) that underwent pre- and postoperative high-resolution esophageal manometry.
Fig. 5 Pre- and postoperative lower esophageal sphincter pressure in the three patients with hypertensive lower esophageal sphincter pressure that underwent pre- and postoperative high-resolution esophageal manometry. © 2015 International Society for Diseases of the Esophagus
Motility disorders of the esophagus
and spastic motility disorders of the esophagus. Some authors have reported that patients with hypercontractile esophagus rarely, if ever, experience normalization of motility with medical antireflux treatment.21,22 In this study, 38 patients with spastic motility disorders who underwent LNF demonstrated improvement in distal esophageal acid exposure, as well as the manometric abnormality in those few patients who also agreed to have HRM performed in the follow-up period. Certainly, the retrospective nature of this study is one of its more important limitations. In particular, the use of the Chicago classification system in the diagnosis of NE, JHE, and DES and the use of a more ‘conventional’ classification in the definition of HTLES, an entity that has been long recognized at our institution, is reflective of the fact that the data were collected in the ‘transitional’ period in the evolution of the interpretation of HRM. Further, until very recently it has been relatively challenging to obtain some of the metrics used in the Chicago classification with the instrumentation and software that was available to us at the time the individual manometric procedures were performed.23 Although the Chicago Classification divides the Jackhammer esophagus and Nutcracker esophagus in a hierarchical fashion based on a DCI cutoff of 8000 mmHg/cm/second, we included two JHE patients in the NE group for two main reasons: first, similarly to other authors, we believe that Jackhammer esophagus represents the extreme condition of esophageal hypercontractility and that some of them are associated with reflux, thus making them appropriate for inclusion with the NE group, and second that the relatively uncommon incidence of JHE (only two patients in our cohort) makes isolated analysis for the endpoints of our study more difficult to interpret.24 Given the above-mentioned longstanding recognition of HTLES as a manometric finding by our group, we were very interested in including these patients in this analysis. However, this specific entity is not defined in the 2012 Chicago classification system;10 hence, we opted to use a more ‘conventional’ classification for this particular diagnosis.11 Although the clinical implications of HTLES in the lower range of hypertension are uncertain, we believe that this entity is worthy of further study and should still be considered, particularly for patients with LES pressures in the higher ranges. Unfortunately, while many of the patients in this study agreed to pH testing after surgery, only six were also willing to repeat the manometry due to discomfort with the procedure. Thus, positioning of the pH catheter in 32 patients was based on the preoperative manometric location of the LES. We recognize that this is potentially problematic, as the anatomic modification of a Nissen fundoplication is likely to change © 2015 International Society for Diseases of the Esophagus
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the position of the LES, possibly leading to a false negative result of the pH study because of the pH probe being situated up to 3 cm or 4 cm higher than 5 cm above the manometrically defined proximal border of the LES. However, given the very marked decrease in pH values and DeMeester scores together with improvement in reflux related symptoms, we feel that these data are still of some value, though understandably it must be interpreted with caution. Although our preop pH data are suggestive of the concept that esophageal acid exposure may play a role in the development of spastic disorders of the esophagus, it is not possible to conclude that the motility abnormality is caused by the presence of abnormal esophageal acid exposure, particularly with the small numbers of patients who had motility testing postoperatively. However, given these findings, we believe that hypermotility disorders are not a contraindication to antireflux surgery in patients who have objective evidence of abnormal distal esophageal acid exposure. Therefore, it is our practice to recommend an antireflux operation in patients with these motility disorders and GERD, in order to normalize distal esophageal acid exposure and achieve improvement in the reflux-related symptoms that are frequently observed in this group of patients.
CONCLUSIONS In patients with all hypermotility disorders, 24-hour pH monitoring reveals abnormal distal esophageal acid exposure in the majority of patients who report typical reflux symptoms and almost half of those patients with respiratory symptoms. In contrast, GERD was not present in the majority of patients with hypermotility disorders whose dominant symptoms are dysphagia or chest pain. For those patients with GERD, LNF is effective at relieving reflux related symptoms such as heartburn, regurgitation, and respiratory symptoms. In addition, manometric abnormalities appear to improve in these patients after LNF. Taken together, these findings suggest that it is abnormal esophageal acid exposure rather than the motility disorder itself that produces the predominant symptoms in this subset of patients. References 1 Fouad Y M, Katz P O, Hatlebakk J G, Castell D O. Ineffective esophageal motility: the most common motility abnormality in patients with GERD-associated respiratory symptoms. Am J Gastroenterol 1999; 94: 1464–7. 2 Patti M G, Debas H T, Pellegrini C A. Clinical and functional characterization of high gastroesophageal reflux. Am J Surg 1993; 165: 163–6, discussion 166–8. 3 Savarino E, Gemignani L, Pohl D et al. Oesophageal motility and bolus transit abnormalities increase in parallel with the severity of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2011; 34: 476–86.
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4 Mentore R, Balestrieri P, Emerenziani S, Guarino M P L, Cicala M. Weak peristalsis with large breaks is associated with higher acid exposure and delayed reflux clearance in the supine position in GERD patients. Am J Gastroenterol 2014; 109: 46–51. 5 Lord R V N, DeMeester S R, Peters J H et al. Hiatal hernia, lower esophageal sphincter incompetence, and effectiveness of Nissen fundoplication in the spectrum of gastroesophageal reflux disease. J Gastrointest Surg 2009; 13: 602–10. 6 Herbella F A, Tineli A C, Wilson J R Jr, Del Grande J C. Surgical treatment of primary esophageal motility disorders. J Gastrointest Surg 2008; 12: 604–8. 7 Roman S, Kahrilas P J. Distal esophageal spasm. Dysphagia 2012; 27: 115–23. 8 Tutuian R, Castell D O. Esophageal motility disorders (distal esophageal spasm, nutcracker esophagus, and hypertensive lower esophageal sphincter): modern management. Curr Treat Options Gastroenterol 2006; 9: 283–94. 9 Woltman T A, Oelschlager B K, Pellegrini C A. Surgical management of esophageal motility disorders. J Surg Res 2004; 117: 34–43. 10 Bredenoord A J, Fox M, Kahrilas P J et al. Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography (EPT). Neurogastroenterol Motil 2012; 24 (Suppl. 1): 57–65. doi: 10.1111/ j.1365-2982.2011.01834.x 11 Salvador R, Dubecz A, Polomsky M et al. A new era in esophageal diagnostics: the image-based paradigm of high-resolution manometry. J Am Coll Surg 2009; 208: 1035–44. doi: 10.1016/ j.jamcollsurg.2009.02.049; [Epub 2009 Apr 24]. 12 Osgood H. A peculiar form of oesophagismus. Boston Med Surg J 1889; 120: 401–5. 13 Almansa C, Heckman M G, DeVault K R, Bouras E, Achem S R. Esophageal spasm: demographic, clinical, radiographic, and manometric features in 108 patients. Dis Esophagus 2012; 25: 214–21. 14 Lufrano R, Heckman M G, Diehl N, Devault K R, Achem S R. Nutcracker esophagus: demographic, clinical features, and esophageal tests in 115 patients. Dis Esophagus 2015; 28 (1): 11–18.
15 Herbella F A M, Raz D J, Nipomnick I, Patti M G. Primary versus secondary esophageal motility disorders: diagnosis and implications for treatment. J Laparoendosc Adv Surg Tech 2009; 19: 195–8. 16 Patti M G, Pellegrini C A, Arcerito M, Tong J, Mulvihill S J, Way L W. Comparison of medical and minimally invasive surgical therapy for primary esophageal motility disorders. Arch Surg 1995; 130: 609–15. 17 Tutuian R, Castell D O. Review article: oesophageal spasm, diagnosis and management. Aliment Pharmacol Ther 2006; 23: 1393–402. 18 Oelschlager B K, Petersen R P, Brunt L M et al. Laparoscopic paraesophageal hernia repair: defining long-term clinical and anatomic outcomes. J Gastrointest Surg 2012; 16: 453–9. 19 Soares R V, Montenovo M, Pellegrini C A, Oelschlager B K. Laparoscopy as the initial approach for epiphrenic diverticula. Surg Endosc 2011; 25: 3740–6. 20 Barreca M, Oelschlager B K, Pellegrini C A. Outcomes of laparoscopic Nissen fundoplication in patients with the ‘hypercontractile esophagus’. Arch Surg 2002; 137: 724–8, discussion 729. 21 Achem S R, Kolts B E, Wears R, Burton L, Richter J E. Chest pain associated with nutcracker esophagus: a preliminary study of the role of gastroesophageal reflux. Am J Gastroenterol 1993; 88: 187–92. 22 Adamek R J, Wegener M, Wienbeck M, Pulte T. Esophageal motility disorders and their coexistence with pathologic acid reflux in patients with noncardiac chest pain. Scand J Gastroenterol 1995; 30: 833–8. 23 Do Carmo G C, Jafari J, Sifrim D, De Oliveira R B. Normal esophageal pressure topography metrics for data derived from the Sandhill-Unisensor high-resolution manometry assembly in supine and sitting positions. Neurogastroenterol Motil 2015; 27: 285–92. doi: 10.1111/nmo.12501 24 Roman S, Pandolfino J E, Chen J, Boris L, Luger D, Kahrilas P J. Phenotypes and clinical context of hypercontractility in high-resolution esophageal pressure topography (EPT). Am J Gastroenterol 2012; 107: 37–45. doi: 10.1038/ajg.2011.313; [Epub 2011 Sep 20].
© 2015 International Society for Diseases of the Esophagus
Original article
Esophageal hypermotility: cause or effect? O. M. Crespin, R. P. Tatum, R. B. Yates, M. Sahin, K. Coskun, A. V. Martin, A. Wright, B. K. Oelschlager, C. A. Pellegrini University of Washington, Surgery, Seattle, WA, USA
Summary. Nutcracker esophagus (NE), Jackhammer esophagus (JHE), distal esophageal spasm (DES), and hypertensive lower esophageal sphincter (HTLES) are defined by esophageal manometric findings. Some patients with these esophageal motility disorders also have abnormal gastroesophageal reflux. It is unclear to what extent these patients’ symptoms are caused by the motility disorder, the acid reflux, or both. The aim of this study was to determine the effectiveness of laparoscopic Nissen fundoplication (LNF) on esophageal motility disorders, gastroesophageal reflux, and patient symptoms. Between 2007 and 2013, we performed high-resolution esophageal manometry on 3400 patients, and 221 patients were found to have a spastic esophageal motility disorder. The medical records of these patients were reviewed to determine the manometric abnormality, presence of gastroesophageal symptoms, and amount of esophageal acid exposure. In those patients that underwent LNF, we compared pre- and postoperative esophageal motility, gastroesophageal symptom severity, and esophageal acid exposure. Of the 221 patients with spastic motility disorders, 77 had NE, 2 had JHE, 30 had DES, and 112 had HTLES. The most frequently reported primary and secondary symptoms among all patients were: heartburn and/or regurgitation, 69.2%; respiratory, 39.8%; dysphagia, 35.7%; and chest pain, 22.6%. Of the 221 patients, 192 underwent 24-hour pH monitoring, and 103 demonstrated abnormal distal esophageal acid exposure. Abnormal 24-hour pH monitoring was detected in 62% of patients with heartburn and regurgitation, 49% of patients with respiratory symptoms, 36.8 % of patients with dysphagia, and 32.6% of patients with chest pain. Sixty-six of the 103 patients with abnormal 24-hour pH monitoring underwent LNF. Thirty-eight (13NE, 2JHE, 6 DES, and 17 HTLES) of these 66 patients had a minimum of 6-month postoperative follow-up that included clinical evaluation, esophageal manometry, and 24-hour pH monitoring. Postoperatively, all 38 patients had normal distal esophageal acid exposure. Of these 38 patients, symptoms resolved in 28 and improved in 10. Of six patients (one with NE, two JHE, and three with HTLES) that underwent postoperative esophageal manometry, five exhibited normal motility. Typical reflux symptoms are common among patients with esophageal hypermotility disorders. Abnormal 24-hour pH monitoring is present in the majority of patients with who report typical reflux symptoms and almost half of patients who report respiratory symptoms. Conversely, the majority of patients who report dysphagia or chest pain have normal distal esophageal acid exposure. Based on a small number of patients in this study, it also appears that motility disorders often improve after LNF. LNF is associated with resolution or improvement in reflux related symptoms and esophageal motility parameters in patients exhibiting abnormal esophageal acid exposure. This suggests that patient symptoms are due to abnormal acid exposure and not the motility disorder. KEY WORDS: distal esophageal spasm, esophageal spastic motility disorders, gastroesophageal reflux disease, hypertensive lower esophageal sphincter, laparoscopic Nissen fundoplication, nutcracker esophagus.
Address correspondence to: Roger Tatum, MD, University of Washington, Surgery, Seattle, WA 98195, USA. Email: [email protected] This study was performed at University of Washington Medical Center. The content of this study has not been published elsewhere. This study was accepted and presented as poster at Digestive Disease Week 2014. This study was reviewed and approved by the University of Washington Investigational Review Board, #46445-EA. All authors have no financial support or relationships that may pose conflict of interest. © 2015 International Society for Diseases of the Esophagus
INTRODUCTION Recent studies have demonstrated an association between gastroesophageal reflux disease (GERD) and some esophageal motility disorders. For example, GERD has been identified in patients with hypocontractile esophagus – a motility disorder characterized by a hypotensive lower esophageal sphincter (LES) and ineffective esophageal motility1–5 1
2
Diseases of the Esophagus
Furthermore, in patients with hypocontractile esophagus, there appears to be a positive correlation between the degree abnormal acid exposure, the severity of the LES abnormality, and the presence of typical reflux symptoms. The link between GERD and hypermotility disorders – Nutcracker esophagus (NE), Jackhammer esophagus JHE, distal esophageal spasm (DES), and hypertensive lower esophageal sphincter (HTLES) – is less clear. Some of these patients may describe dysphagia or chest pain while some others will primarily complain of heartburn and regurgitation or a combination of all of these symptoms. To what extent the motility disorder or the acid reflux is responsible for these patients’ complaints remains controversial. Thus, the optimal treatment for patients with concomitant spastic motility disorders and GERD is not established.6–9 Therefore, the aim of this study was to evaluate symptom presentation, the presence of GERD, and the effect of antireflux surgery (laparoscopic Nissen fundoplication, LNF) in patients with esophageal hypermotility disorders of the esophagus. METHODS Between 2008 and 2012, 3400 high-resolution manometry (HRM) studies were performed at the University of Washington Medical Center in Seattle, Washington. Hypermotility disorders were diagnosed in 221 patients, who were referred for surgical evaluation. This study was reviewed and approved by the University of Washington Investigational Review Board, #46445-EA. Patient symptoms Clinical records were reviewed for primary and secondary symptoms reported by patients. Because of the retrospective nature of this review, a specific symptom scale was not used, rather merely an identification of the symptoms that drove the patient to seek evaluation, and whether or not these were the main symptom or an additional associated symptom. Respiratory symptoms included cough, hoarseness, sore throat, dyspnea, and shortness of breath. Postoperatively, patient symptoms were rated as resolved (all primary and secondary symptoms disappeared entirely), improved (reduction in severity of all primary and secondary symptoms), or unchanged (symptom severity was the same or worse compared with preoperatively, or the patient developed new symptoms). In 38 patients that underwent LNF, clinical notes were collected at a mean of 12 months (range 6–48 months) postoperatively. 24-hour pH monitoring Ambulatory 24-hour pH monitoring was performed using a dual-channel catheter. The distal channel was
positioned 5 cm above the manometrically determined LES, and the proximal channel was located 10 centimeters above the distal channel. A portable digital data logger was used to record pH fluctuations, and the patient recorded symptoms in an event diary. The information was analyzed using a Digitrapper and Synectics Software. Abnormal distal esophageal acid exposure was present when the total percent of time pH below 4 was greater than 4.5% or the De Meester score higher than 14.7. High-resolution manometry and spastic motility disorders High-resolution manometry was performed using a 32-sensor solid-state catheter and the Insight Acquisition System. Analysis was completed using BioVIEW Analysis esophageal manometry software (Sandhill Scientific, Inc., Colorado). The diagnosis of motility disorders was performed according to the Chicago classification; however, we also included the clinical entity of HTLES from previous manometric classifications using the criteria described by Salvador and colleagues.10,11
RESULTS Of 3400 high-resolution manometry procedures performed during the study period, 221 patients (132 female, mean age 58 years, range 19–91) were identified as having one of the esophageal hypercontractility disorders (77 NE, 2 JHE, 30 DES, 112 HTLES). Among these patients, 153 (69.2%) reported symptoms of heartburn or regurgitation, 88 (39.8%) reported respiratory symptoms including cough or hoarseness, 79 (35.7%) reported dysphagia, and 50 (22.6%) reported chest pain. The distribution of symptom frequency for each motility disorder is shown in Figures 1–3; for simplicity, jackhammer esophagus was included in the NE group. 24-hour pH monitoring Twenty-nine patients did not undergo 24-hour pH monitoring prior to LNF due to the presence of an epiphrenic diverticulum or large paraesophageal hernia. In 192 patients that underwent 24-hour pH monitoring, 103 (53.6%) patients had abnormal distal esophageal acid exposure. There was no difference in the frequency of abnormal 24-hour pH monitoring among the specific spastic motility disorders: NE (including 2 JHE), 57%; DES, 64%; and HTLES, 49% (p = 0.35). Abnormal 24-hour pH monitoring with an acid-reflux pattern (as opposed to a fermentation pattern which is sometimes seen in patients with achalasia) was present in 64% of patients with typical reflux symptoms and in 49% of patients who reported © 2015 International Society for Diseases of the Esophagus
Motility disorders of the esophagus
3
respiratory symptoms, which was significantly higher than was observed in patients complaining primarily of dysphagia (37%) or chest pain (33%, P < 0.001 for both). Symptom correlation data was available for 171 of the patients who underwent 24-hour pH monitoring. Table 1 demonstrates that for patients with an abnormal pH study, the symptom index was much more likely to be positive (>50%) for reflux symptoms (heartburn and/or regurgitation) and dysphagia than for chest pain or respiratory symptoms.
Outcomes of laparoscopic Nissen fundoplication in patients with spastic motility Laparoscopic Nissen Fundoplication was performed in 66 of 103 (64%) of patients with abnormal 24-hour pH monitoring. Of the 37 patients that did not undergo LNF, seven patients declined the operation, seven patients were recommended to undergo gastric bypass rather than LNF due to concomitant obesity, and surgery was contraindicated in 23 patients due to comorbid medical conditions. Thirty-eight LNF patients had a minimum of 6 months of follow-up data; these included 13 NE, 2 JHE, 6 DES, and 17 HTLES. Of these, 28 (74%) patients reported symptom resolution and 10 (24%) reported symptom improvement. All of these patients demonstrated normalization of distal esophageal acid exposure on postoperative 24-hour pH monitoring (Tables 2 and 3). At a mean of 8 months (range 6 to 12 months) postoperatively, six patients underwent HRM. Figures 4 and 5 demonstrate postoperative improvement in the key esophageal manometric parameters for one patient with preoperative evidence of NE, 2 with JHE, and three patients with preoperative HTLES.
DISCUSSION
Figs 1–3 Distribution of symptom frequency among patients with motility disorders. Symptoms reported were either primary (dominant) symptoms or secondary symptoms reported in association with other symptoms (Reflux symptoms: heartburn and regurgitation; Respiratory symptoms: cough, hoarseness, sore throat, dyspnea, and shortness of breath).
Although chest pain and dysphagia are the symptoms that are commonly associated with spastic motility disorders of the esophagus,12–14 the most frequent symptoms in our patient population were heartburn and/or regurgitation followed by respiratory symptoms. In concordance with other authors, we do not believe that symptoms alone can distinguish primary motility disorders from disorders associated with
Table 1 Symptom Index in 171 patients reporting symptoms during 24-hour pH monitoring Symptom index %, median (range)
Normal acid exposure (n = 81) Patients with abnormal acid exposure (n = 90)
Reflux (heartburn/ regurgitation)
Dysphagia
Respiratory
Chest pain
21 (0–75) 78 (0–100)
17 (0–66) 50 (0–89)
7 (0–35) 34 (0–81)
5 (0–47) 10 (0–87)
© 2015 International Society for Diseases of the Esophagus
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Diseases of the Esophagus
Table 2 Results of pre- and postoperative 24-hour pH monitoring in 38 patients with spastic motility disorders. All values are reported as mean (range)
Total % time pH < 4 DeMeester score
Preoperative
Postoperative
10.6 (4.8–23.1) 28.6 (15.1–97.3)
2.03 (0.8–3.7) 5.1 (1.1–9.9)
Table 3 The effect of laparoscopic Nissen fundoplication on severity of primary and secondary symptoms reported by 38 patients with hypercontractility disorders Motility disorder
Symptom resolution
Symptom improvement
No improvement
NE (13) JHE (2) DES (6) HTLES (17) Total (38)
10 2 4 12 28
3 – 2 5 10
0 0 0 0 0
DES, distal esophageal spasm; JHE, Jackhammer esophagus; HTLES, hypertensive lower esophageal sphincter; NE, Nutcracker esophagus.
reflux (the so-called ‘secondary’ motility disorders)15,16 Our data support this: abnormal 24-hour pH monitoring was identified in the majority of patients with heartburn and/or regurgitation as well as almost half of patients with respiratory symptoms. Moreover, the majority of patients with chest pain or dysphagia did not have abnormal pH studies. Contrary to some clinicians who prefer to start treating patients with spastic motility disorders and GERD symptoms with an empiric trial of protonpump inhibitors, we believe that performance of both esophageal manometry and 24-hour pH monitoring is essential to correctly identify the causative disorder and formulate an appropriate treatment plan because it is impossible to determine based solely on symptoms whether the underlying disorder is one of motility or reflux.15–17 In our clinic, we have observed two distinct referral patterns that support this practice. In the first, patients who are referred for antireflux surgery and undergo preoperative esophageal manometry are found to have a previously undiagnosed motility abnormality. In the second, patients who are referred for further workup of a suspected or already-identified esophageal motility abnormality and undergo 24-hour pH monitoring are found to have abnormal esophageal acid exposure. In both situations, we consider that the performance of both esophageal manometry and 24-hour pH monitoring is essential in guiding treatment recommendations. The two exceptions to this practice occur in patients with either a large paraesophageal hernia or an epiphrenic diverticulum, in which case we perform esophageal manometry but not 24-hour pH monitoring. In the presence of a large paraesophageal hernia, accurate placement of the distal channel on the pH
catheter is very difficult, increasing the likelihood of invalid results. Further, paraesophageal hernia and epiphrenic diverticula are anatomic abnormalities that require operative repair to relieve obstructive symptoms; the results of 24-hour pH monitoring are unlikely to alter the recommendation for surgical repair.18,19 Finally, we routinely perform an antireflux procedure as part of these operations with good results. Hence, 29 of our patients with one of these motility disorders did not undergo pH monitoring prior to LNF. When reflux was present, we observed very good control of both esophageal acid exposure and patient symptoms with LNF. We have previously reported our initial experience in performing this procedure in patients with NE and HTLES associated with GERD.20 Since then, we have been offering this operation to that subset of patients. In this study, we report similar favorable results in six patients with DES and GERD. It is very difficult to demonstrate a cause and effect relationship between distal esophageal acid exposure
Fig. 4 Pre- and postoperative distal contractile integral (DCI) in one patient with Nutcracker esophagus (NE) and two patients with Jackhammer esophagus (JHE) that underwent pre- and postoperative high-resolution esophageal manometry.
Fig. 5 Pre- and postoperative lower esophageal sphincter pressure in the three patients with hypertensive lower esophageal sphincter pressure that underwent pre- and postoperative high-resolution esophageal manometry. © 2015 International Society for Diseases of the Esophagus
Motility disorders of the esophagus
and spastic motility disorders of the esophagus. Some authors have reported that patients with hypercontractile esophagus rarely, if ever, experience normalization of motility with medical antireflux treatment.21,22 In this study, 38 patients with spastic motility disorders who underwent LNF demonstrated improvement in distal esophageal acid exposure, as well as the manometric abnormality in those few patients who also agreed to have HRM performed in the follow-up period. Certainly, the retrospective nature of this study is one of its more important limitations. In particular, the use of the Chicago classification system in the diagnosis of NE, JHE, and DES and the use of a more ‘conventional’ classification in the definition of HTLES, an entity that has been long recognized at our institution, is reflective of the fact that the data were collected in the ‘transitional’ period in the evolution of the interpretation of HRM. Further, until very recently it has been relatively challenging to obtain some of the metrics used in the Chicago classification with the instrumentation and software that was available to us at the time the individual manometric procedures were performed.23 Although the Chicago Classification divides the Jackhammer esophagus and Nutcracker esophagus in a hierarchical fashion based on a DCI cutoff of 8000 mmHg/cm/second, we included two JHE patients in the NE group for two main reasons: first, similarly to other authors, we believe that Jackhammer esophagus represents the extreme condition of esophageal hypercontractility and that some of them are associated with reflux, thus making them appropriate for inclusion with the NE group, and second that the relatively uncommon incidence of JHE (only two patients in our cohort) makes isolated analysis for the endpoints of our study more difficult to interpret.24 Given the above-mentioned longstanding recognition of HTLES as a manometric finding by our group, we were very interested in including these patients in this analysis. However, this specific entity is not defined in the 2012 Chicago classification system;10 hence, we opted to use a more ‘conventional’ classification for this particular diagnosis.11 Although the clinical implications of HTLES in the lower range of hypertension are uncertain, we believe that this entity is worthy of further study and should still be considered, particularly for patients with LES pressures in the higher ranges. Unfortunately, while many of the patients in this study agreed to pH testing after surgery, only six were also willing to repeat the manometry due to discomfort with the procedure. Thus, positioning of the pH catheter in 32 patients was based on the preoperative manometric location of the LES. We recognize that this is potentially problematic, as the anatomic modification of a Nissen fundoplication is likely to change © 2015 International Society for Diseases of the Esophagus
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the position of the LES, possibly leading to a false negative result of the pH study because of the pH probe being situated up to 3 cm or 4 cm higher than 5 cm above the manometrically defined proximal border of the LES. However, given the very marked decrease in pH values and DeMeester scores together with improvement in reflux related symptoms, we feel that these data are still of some value, though understandably it must be interpreted with caution. Although our preop pH data are suggestive of the concept that esophageal acid exposure may play a role in the development of spastic disorders of the esophagus, it is not possible to conclude that the motility abnormality is caused by the presence of abnormal esophageal acid exposure, particularly with the small numbers of patients who had motility testing postoperatively. However, given these findings, we believe that hypermotility disorders are not a contraindication to antireflux surgery in patients who have objective evidence of abnormal distal esophageal acid exposure. Therefore, it is our practice to recommend an antireflux operation in patients with these motility disorders and GERD, in order to normalize distal esophageal acid exposure and achieve improvement in the reflux-related symptoms that are frequently observed in this group of patients.
CONCLUSIONS In patients with all hypermotility disorders, 24-hour pH monitoring reveals abnormal distal esophageal acid exposure in the majority of patients who report typical reflux symptoms and almost half of those patients with respiratory symptoms. In contrast, GERD was not present in the majority of patients with hypermotility disorders whose dominant symptoms are dysphagia or chest pain. For those patients with GERD, LNF is effective at relieving reflux related symptoms such as heartburn, regurgitation, and respiratory symptoms. In addition, manometric abnormalities appear to improve in these patients after LNF. Taken together, these findings suggest that it is abnormal esophageal acid exposure rather than the motility disorder itself that produces the predominant symptoms in this subset of patients. References 1 Fouad Y M, Katz P O, Hatlebakk J G, Castell D O. Ineffective esophageal motility: the most common motility abnormality in patients with GERD-associated respiratory symptoms. Am J Gastroenterol 1999; 94: 1464–7. 2 Patti M G, Debas H T, Pellegrini C A. Clinical and functional characterization of high gastroesophageal reflux. Am J Surg 1993; 165: 163–6, discussion 166–8. 3 Savarino E, Gemignani L, Pohl D et al. Oesophageal motility and bolus transit abnormalities increase in parallel with the severity of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2011; 34: 476–86.
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4 Mentore R, Balestrieri P, Emerenziani S, Guarino M P L, Cicala M. Weak peristalsis with large breaks is associated with higher acid exposure and delayed reflux clearance in the supine position in GERD patients. Am J Gastroenterol 2014; 109: 46–51. 5 Lord R V N, DeMeester S R, Peters J H et al. Hiatal hernia, lower esophageal sphincter incompetence, and effectiveness of Nissen fundoplication in the spectrum of gastroesophageal reflux disease. J Gastrointest Surg 2009; 13: 602–10. 6 Herbella F A, Tineli A C, Wilson J R Jr, Del Grande J C. Surgical treatment of primary esophageal motility disorders. J Gastrointest Surg 2008; 12: 604–8. 7 Roman S, Kahrilas P J. Distal esophageal spasm. Dysphagia 2012; 27: 115–23. 8 Tutuian R, Castell D O. Esophageal motility disorders (distal esophageal spasm, nutcracker esophagus, and hypertensive lower esophageal sphincter): modern management. Curr Treat Options Gastroenterol 2006; 9: 283–94. 9 Woltman T A, Oelschlager B K, Pellegrini C A. Surgical management of esophageal motility disorders. J Surg Res 2004; 117: 34–43. 10 Bredenoord A J, Fox M, Kahrilas P J et al. Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography (EPT). Neurogastroenterol Motil 2012; 24 (Suppl. 1): 57–65. doi: 10.1111/ j.1365-2982.2011.01834.x 11 Salvador R, Dubecz A, Polomsky M et al. A new era in esophageal diagnostics: the image-based paradigm of high-resolution manometry. J Am Coll Surg 2009; 208: 1035–44. doi: 10.1016/ j.jamcollsurg.2009.02.049; [Epub 2009 Apr 24]. 12 Osgood H. A peculiar form of oesophagismus. Boston Med Surg J 1889; 120: 401–5. 13 Almansa C, Heckman M G, DeVault K R, Bouras E, Achem S R. Esophageal spasm: demographic, clinical, radiographic, and manometric features in 108 patients. Dis Esophagus 2012; 25: 214–21. 14 Lufrano R, Heckman M G, Diehl N, Devault K R, Achem S R. Nutcracker esophagus: demographic, clinical features, and esophageal tests in 115 patients. Dis Esophagus 2015; 28 (1): 11–18.
15 Herbella F A M, Raz D J, Nipomnick I, Patti M G. Primary versus secondary esophageal motility disorders: diagnosis and implications for treatment. J Laparoendosc Adv Surg Tech 2009; 19: 195–8. 16 Patti M G, Pellegrini C A, Arcerito M, Tong J, Mulvihill S J, Way L W. Comparison of medical and minimally invasive surgical therapy for primary esophageal motility disorders. Arch Surg 1995; 130: 609–15. 17 Tutuian R, Castell D O. Review article: oesophageal spasm, diagnosis and management. Aliment Pharmacol Ther 2006; 23: 1393–402. 18 Oelschlager B K, Petersen R P, Brunt L M et al. Laparoscopic paraesophageal hernia repair: defining long-term clinical and anatomic outcomes. J Gastrointest Surg 2012; 16: 453–9. 19 Soares R V, Montenovo M, Pellegrini C A, Oelschlager B K. Laparoscopy as the initial approach for epiphrenic diverticula. Surg Endosc 2011; 25: 3740–6. 20 Barreca M, Oelschlager B K, Pellegrini C A. Outcomes of laparoscopic Nissen fundoplication in patients with the ‘hypercontractile esophagus’. Arch Surg 2002; 137: 724–8, discussion 729. 21 Achem S R, Kolts B E, Wears R, Burton L, Richter J E. Chest pain associated with nutcracker esophagus: a preliminary study of the role of gastroesophageal reflux. Am J Gastroenterol 1993; 88: 187–92. 22 Adamek R J, Wegener M, Wienbeck M, Pulte T. Esophageal motility disorders and their coexistence with pathologic acid reflux in patients with noncardiac chest pain. Scand J Gastroenterol 1995; 30: 833–8. 23 Do Carmo G C, Jafari J, Sifrim D, De Oliveira R B. Normal esophageal pressure topography metrics for data derived from the Sandhill-Unisensor high-resolution manometry assembly in supine and sitting positions. Neurogastroenterol Motil 2015; 27: 285–92. doi: 10.1111/nmo.12501 24 Roman S, Pandolfino J E, Chen J, Boris L, Luger D, Kahrilas P J. Phenotypes and clinical context of hypercontractility in high-resolution esophageal pressure topography (EPT). Am J Gastroenterol 2012; 107: 37–45. doi: 10.1038/ajg.2011.313; [Epub 2011 Sep 20].
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