Manometric and symptomatic spectrum of motor dysphagia in a tertiary referral center in northern India

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1 Indian J Gastroenterol 2010(January February):29(1):18 22 ORIGINAL ARTICLE Manometric and symptomatic spectrum of motor dysphagia in a tertiary referral center in northern India Asha Misra Dipti Chourasia Uday C. Ghoshal Abstract Background We studied the spectrum of motor dysphagia in a northern Indian tertiary referral center. Methods In this retrospective study, consecutive patients with motor dysphagia referred to the Gastrointestinal Pathophysiology and Motility Laboratory from 2002 to 2007 were evaluated clinically and with eight-channel water-perfusion manometry. Causes of dysphagia were diagnosed using standard criteria. Results Of 250 patients (age 41.3 [15.0] years, 146 men), 193 (77%) had achalasia cardia (AC) and 57 (23%) had other causes (11, 4.4%: diffuse esophageal spasm [DES]; 9, 3.6%: hypertensive lower esophageal sphincter [Hy LES]); manometry was normal in 37 patients. Twenty-seven patients (14%) had vigorous AC. Duration of dysphagia at presentation was longer in those with AC and Hy LES than in normal manometry (NM) (21 months [1 180] vs. 6 [1 360], p = 0.000; 24 months [7 48] vs. 6 [1 360], p = 0.015). Regurgitation and bolus obstruction were more frequent in those with AC than in NM (89/154, 57.79% vs. 3/27, 11.11%, p = ). Heartburn was less frequent in patients with AC than in others (AC: 4/146, 2.73% vs. normal: 4/27, 14.8% [p = 0.02] and others: 3/15, 20% [p = 0.018]). Chest pain was reported by 74/135 (54.8%) classic and 12/19 (63.2%) vigorous AC (p = NS). Patients with NM had lower LES A. Misra D. Chourasia U. C. Ghoshal Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow , India U. C. Ghoshal ( ) udayghoshal@gmail.com Received: 10 April 2009 / Revised: 21 September 2009 / Accepted: 17 October 2009 Indian Society of Gastroenterology 2010 pressure than those with classic AC, Hy LES and vigorous AC (p < in each case). Patients with DES had lower LES pressure than in classic AC, Hy LES and vigorous AC (p = 0.043, p < , and p = 0.002, respectively). Patients with classic AC had lower LES pressure than in Hy LES and vigorous AC (p = 0.024, p = 0.001, respectively). Conclusion Classic AC was the commonest cause of motor dysphagia in our center. AC was associated with higher LES pressure, longer duration of dysphagia, frequent regurgitation and bolus obstruction. Keywords Achalasia cardia diffuse esophageal spasm esophageal manometry hypertensive lower esophageal sphincter Introduction Dysphagia is a common problem in patients with primary motor disorders of the esophagus. These include achalasia cardia (AC), diffuse esophageal spasm (DES), nutcracker esophagus and hypertensive lower esophageal sphincter (Hy LES). Esophageal manometry is the gold standard for diagnosis of these disorders. 1,2 Manometric features of AC are aperistalsis in esophageal body characterized by either simultaneous or no contractions, and incomplete relaxation of LES. 3,4 Achalasia cardia is further classified into classic (average esophageal body amplitude 40 mmhg) and vigorous (average esophageal body amplitude >40 mmhg) types. 5,6 DES is characterized by the following: (1) >10% of esophageal body contractions in response to wet swallows are simultaneous type, (2) mean simultaneous contraction amplitude >30 mmhg, and (3) spontaneous, repetitive and multiple peaked contractions. 7-9 Patients with nutcracker esophagus have very high (mean >180 mmhg) contraction amplitudes in the esophageal body. 10 Lastly, patients with Hy LES have normal pattern of peristalsis in the distal esophagus often associated with abnormally elevated resting LES pressure (>40 mmhg), exaggerated contraction of LES after relaxation, and incomplete relaxation There is scanty data on the manometric and symptomatic spectrum of motor dysphagia in the Indian population. 15 We studied

2 Symptoms and manometry in motor dysphagia 19 (1) the frequency of AC, DES, nutcracker esophagus and Hy LES in patients with motor dysphagia, (2) difference in symptom profile among these patients. Methods In this retrospective study, the case records of 250 adult patients with motor dysphagia referred to the Gastrointestinal Pathophysiology and Motility Laboratory in a tertiary center during a 5-year period (from 2002 to 2007) were analyzed. Patients with a history of dysphagia of at least one month duration were included. Esophageal manometry Esophageal manometry was performed after overnight fast using an eight-channel water perfusion system (RedTech, CA, USA) as described previously. 16 Barium esophagogram and upper gastrointestinal endoscopy findings were recorded where available patients, those with normal manometry had lower LES pressure than those with classic AC, Hy LES and igorous AC (p < , Table 2). Patients with DES had normal LES pressure. Patients with NM had lower LES pressure than in classic AC, Hy LES and vigorous AC (p< in each case). Patients with DES had lower LES pressure than in classic AC, Hy LES and vigorous AC (p=0.043, p < , and p=0.002, respectively). Patients with classic AC had lower LES pressure than in Hy LES and vigorous AC (p=0.024, p=0.001, respectively). Average esophageal contraction amplitude was 57 mmhg and 17 mmhg among patients with vigorous AC and classic AC, respectively. Patients with DES and Hy LES had higher amplitude of contractions in the distal than in the proximal esophageal body. The duration of the contractions in distal esophagus (5 cm above LES) in each group was higher than in the middle esophagus (10-15 cm above LES). The velocity in each group was within normal range (3-5 cm/s) except in patients with AC. 18 Symptom profile All patients were evaluated for symptoms such as regurgitation, chest pain, heartburn, bolus obstruction, globus sensation, respiratory symptoms and weight loss. Symptom frequency was graded as none, occasional ( 1/week) and frequent ( 2/week), whereas weight loss was evaluated as a binary variable (yes/no). Statistical analysis Continuous unpaired data were analyzed using unpaired t-test. Categorical variables were analyzed using χ 2 tests, with Yates correction as applicable. p values <0.05 were considered significant. Results Mean dysphagia duration among these 250 patients (mean age 41.3 [15.0] y, 146 men) was 32.3 (42.4) months. Duration of dysphagia at presentation was longer in patients with AC and Hy LES than in those with normal manometry (p = and 0.015, respectively, Table 1). Patients with DES had dysphagia duration that overlapped with that in the other groups (p = NS, Table 1). Esophageal manometry Of 250 patients, 193 (77%) had AC and the rest had other causes (11, 4.4%: DES, 9, 3.6%: Hy LES). Manometry was normal in 37 (15%) patients. LES could not be studied in 23 patients, as the manometry catheter could not be passed through the gastroesophageal (GE) junction. In the other Indian J Gastroenterol 2010(January February):29(1):18 22 Barium swallow and esophagogastroduodenoscopy Barium swallow report was available in 194 of 250 patients with dysphagia. Of them, 151 (77.8%) had radiograph suggestive of AC. Six of 194 (3.1%) had sigmoid esophagus, none had epiphrenic diverticula, and 31 of 194 (15.9%) had normal barium radiograph. Esophagogastroduodenoscopy was available in 218 of 250 patients. One hundred and forty-one (64.7%) patients had features suggestive of achalasia cardia, as evidenced by the presence of dilated esophagus and resistance while crossing GE junction. One patient (0.4%) had a circumferential tumor in the lower esophagus, which was confirmed as esophageal carcinoma at histology. The patient had features of AC on manometry, which might be pseudoachalasia. Symptom profile We have grouped patients with DES and Hy LES into one category for the purpose of analysis due to small number of patients in each of these groups. The symptom profile is shown in Table 1. Patients with AC often reported regurgitation and bolus obstruction but globus sensation was uncommon. Patients with AC had frequent regurgitation more often than those with normal manometry and DES + Hy LES. Bolus obstruction was also more frequent among AC than those with normal manometry. Chest pain was comparable among these groups. Patients with AC reported infrequent heartburn than those with normal manometry and DES + Hy LES. However, patients with AC had infrequent globus sensation than those with normal manometry and with DES + Hy LES. The frequency 1 Springer

3 20 Misra, et al. Table 1 Demographic and clinical parameters of various groups of patients with motor dysphagia Normal Achalasia Diffuse manometry cardia esophageal Hy LES (n=37) (n=193) spasm (n=11) (n=9) p-value* Age (median [range]) 38 (18-72) 39 (13-88) 47 (13-68) 36 (20-73) NS Male gender (%) 23 (62.2) 116 (60.1) 4 (36.4) 3 (33.3) NS Dysphagia duration (mo.) 6 (1-360) 21(1-180) 6.5 (1-156) 24 (7-48) NM vs. AC=0.000 NM vs. Hy LES=0.015 Symptom profile Occasional Frequent Occasional Frequent Occasional # Frequent p-value Regurgitation 8/27 (29.6) 3/27 (11.1) 32/154 (20.7) 89/154 (57.8) 4/15 (26.6) 4/15 (26.6) NM vs. AC= AC vs. others=0.041 Chest pain 15/29 (51.7) 1/29 (3.4) 78/154 (50.6) 8/154 (5.2) 6/15 (40) 2/15 (13.3) NS Heartburn 7/27 (26) 4/27 (14.8) 42/146 (28.7) 4/146 (2.7) 5/15 (33.3) 3/15 (20) NM vs. AC=0.021 AC vs. others=0.018 Bolus obstruction 14/29 (48.3) 9/29 (31) 23/147 (15.6) 115/147 (78.2) 3/13 (23.3) 7/13 (53.8) NM vs. AC= Globus sensation 10/25 (40) 1/25 (4) 26/143 (18.2) 6/143 (4.2) 3/10 (30) 3/10 (30) AC vs. others=0.013 Respiratory problem 3/28 (10.7) 2/28 (7.1) 29/149 (19.4) 13/149 (8.7) 5/13 (38.4) 1/13 (7.7) NS Weight loss 18/27 (66.7) 97/134 (72.4) 10/13 (76.9) NS Continuous data are shown in median (range); symptom profile is shown as n (%) *Mann Whitney U-test. Chi-squared test with Yate s correction as applicable was used for comparison of categorical data #: Symptom frequency for DES and HyLES NM: normal manometry; AC: achalasia cardia; DES: diffuse esophageal spasm; Hy LES: hypertensive lower esophageal sphincter Table 2 Manometric parameters in motor dysphagia Normal manometry Achalasia cardia (n=193) DES Hy LES Parameters (n=37) Vigorous Classic (n=11) (n=9) LES pressure (mmhg) 20 (7-41) 60 (13-99) 40 (5-95) 27 (7-51) 58 (40-64) Amplitude 20 cm above LES 19 (4-72) 63 (40-112) 17 (4-40) 17 (6-29) 29 (5-71) 15 cm above LES 27 (3-72) 57 (11-153) 17 (3-58) 18 (6-123) 30 (14-108) 10 cm above LES 38 (6-173) 57 (12-106) 17 (2-55) 46 (11-208) 46 (14-145) 5 cm above LES 39 (24-168) 57 (12-109) 17 (3-63) 62.5 (18-118) 70 (38-89) Duration 20 cm above LES 2 (1-19) 6 (1-34) 4 (2-9) 3 (1-6) 15 cm above LES 4 (1-10) 7 (1-34) 6 (2-10) 5 (3-25) 10 cm above LES 5 (2-13) 7 (2-36) 5 (3-11) 5 (4-7) 5 cm above LES 7 (3-13) 8 (1-34) 7.5 (5-12) 7 (4-12) Velocity 3 (1-18) 0 (0-0) 4 (0-10) 5 (3-10) All data are shown as median (range) DES: diffuse esophageal spasm; LES: lower esophageal sphincter; Hy LES: hypertensive LES

4 Symptoms and manometry in motor dysphagia 21 of respiratory symptoms (chronic cough or nocturnal coughing spells) and weight loss were comparable among the groups. Discussion Our study shows that: (1) AC, particularly the classic type, is the commonest cause of motor dysphagia in a tertiary care center, (2) AC is associated with higher LES pressure, longer duration of dysphagia, frequent regurgitation and bolus obstruction than patients with normal manometry findings. Patients presenting with dysphagia without a mechanical cause on endoscopy and/or barium swallow were diagnosed as having motor dysphagia. However, esophageal manometry was normal in 15% of them. Conventional manometry with eight ports might miss some patients with esophageal motility disorders that might be picked up by high-resolution manometry with larger number of ports. 19,20 Also, esophageal motility disorder may be intermittent. AC is the second most common disorder in patients presenting with non-cardiac chest pain. 21,22 In one study of 403 patients with dysphagia, ineffective peristalsis was the most common esophageal dysmotility, followed by achalasia and non-specific esophageal motility disorders. 23 Infrequent occurrence of ineffective esophageal motility in our series might be related to the fact that we included patients with dysphagia and not those with isolated heartburn and chest pain; ineffective esophageal motility is common with severe gastroesophageal reflux disease, 24 which may be somewhat less common in Indians. 25 Classic AC was more common than vigorous AC. Vigorous AC represents the early stage of achalasia. 26 Early stages of AC are not diagnosed by esophagogastroduodenoscopy or barium swallow radiograph, the methods by which physicians generally suspect AC. Patients with vigorous AC had higher LES pressure than in classic AC, probably due to loss of inhibitory neurons, but cholinergic stimulation continues unopposed, leading to high basal LES pressure. 27 Patients with AC had higher LES pressure than patients with normal manometry and DES. It has been proposed that Hy LES and DES are AC in evolution or precursors of AC. The pathophysiology proposed is, initially higher LES pressure (Hy LES), then gradual loss of peristaltic pattern (DES to AC). 26,28 Patients with DES and Hy LES had higher average amplitude of contractions in the esophageal body than the proximal esophagus. Patients with AC had more frequent regurgitation and bolus obstruction than those with normal manometry. Heartburn was more frequent in patients with normal manometry and DES + Hy LES than AC. This finding is difficult to explain. In motor disorder of esophagus, particularly in AC, fermentation of food residue in dilated Indian J Gastroenterol 2010(January February):29(1):18 22 esophagus can cause heartburn. Since patients with AC would have more dilated esophagus than DES and Hy LES, this explanation may not hold good for the observed findings. However, motor disorder and visceral hypersensitivity of esophagus may also explain the heartburn. In conclusion, the present study shows that AC, particularly the classic type, is the most common condition causing motor dysphagia in a tertiary center in northern India. References 1. Dent J, Holloway RH. Esophageal motility and reflux testing. State-of-the-art and clinical role in the twenty-first century. Gastroenterol Clin North Am 1996;25: Dughera L, Cassolino P, Cisaro F, Chiaverina M. Achalasia. Minerva Gastroenterol Dietol 2008;54: Stuart RC, Hennessy TP. Primary disorders of oesophageal motility. 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