Does laparoscopic antireflux surgery prevent the occurrence of transient lower esophageal sphincter relaxation?
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- Bahmeriz, F., Dutta, S., Allen, C. et al. Surg Endosc (2003) 17: 1050. doi:10.1007/s00464-002-8839-1
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Background: Transient lower esophageal sphincter relaxation (TLESR) is the most common mechanism underlying gastroesophageal reflux disease (GERD), causing 70% to 100% of the reflux episodes in normal subjects and 63% to 74% of the reflux episodes in patients with reflux disease. This study aimed to evaluate the effect of laparoscopic Nissen fundoplication on TLESR in patients with proven GERD. Methods: We prospectively followed 73 consecutive patients (13 men and 60 women; mean age, 43.7 ± 1.72 years) with proven diagnosis of GERD and reported TLESRs found during a 40-min esophageal manometric study. These patients had repeat testing 6 months after undergoing laparoscopic Nissen fundoplication. Results: Laparoscopic Nissen fundoplication increased the basal and nadir lower esophageal sphincter (LES) pressure and significantly reduced the number of TLESRs during the manometric study. No patients after surgery exhibited TLESR with nadir less than 2 mmHg. However, 8 of the 73 patients (11%) exhibited TLESR to a nadir exceeding 50% of basal pressure (mean nadir, 5.0 ± 1.07 mmHg). Conclusions: The number of TLESRs is reduced significantly by antireflux surgery. Even accounting for increased basal and nadir pressures, the incidence of TLESR is reduced, suggesting that there may be additional mechanisms involved in this process.
KeywordsTransient lower esophageal sphincter relaxation (TLESR)Laparoscopic fundoplicationGastroesophagcal reflux disease
Gastroesophageal reflux disease (GERD) is the most common upper gastrointestinal disorder in the West, causing symptoms of heartburn and regurgitation in 25% to 30% of the general population. Approximately 10% to 20% of the patients present with complications of GERD. These include esophageal ulceration, stricture formation, intestinal metaplasia of the esophageal lining, and pulmonary complications [5, 17, 18, 22, 25].
Although the specific pathophysiology of reflux remains elusive , transient lower esophageal sphincter relaxation (TLESR) is thought to be the most common mechanism underlying GERD. It represents abrupt decreases in the lower esophageal sphincter (LES) pressure to the level of intragastric pressure not initiated by swallowing. In normal subjects, TLESRs account for 70% to 100% of reflux episodes, and 40% to 74% of such episodes in patients with GERD [9, 20, 21].
The effect of open antireflux surgery on TLESR [14, 16, 24] has been examined by a few studies conducted with a small number of patients. These studies have suggested that fundoplication may have two effects: partial reduction in the rate of TLESRs and a reduction in the proportion of TLESRs accompanied by reflux. So far, no studies have evaluated the effect of laparoscopic Nissen fundoplication (LNF) on the TLESR rate in a large cohort of patients. We prospectively followed 73 patients with documented GERD and TLESR who underwent LNF to determine the effect of this procedure on the incidence of TLESR.
Patients and methods
We prospectively followed 73 consecutive patients (13 men and 60 women; mean age, 43.7 ± 1.72 years) with a proven preoperative diagnosis of GERD in a 24-h ambulatory pH study and report our finding of TLESRs on esophageal manometry. The patients also had an upper gastrointestinal endoscopy and GERD symptom score assessment. All the patients either had intractable reflux symptoms that were not controlled by medical therapy or did not want to take long-term antireflux medication and were referred for laparoscopic antireflux surgery. Of the 73 patients, 18 (25%) had a hiatal hernia. No patient had undergone previous gastric or esophageal surgery. It was expected that all the patients would complete the pre- and postoperative evaluations.
Esophageal manometry was performed with a seven-lumen sleeve-sidehole catheter (Dent Sleeve, Adelaide, Australia). After topical anesthesia of the nostril, the catheter was introduced nasally and positioned with sleeves straddling the LES. The patient then was allowed to accommodate to the tube for 10 min. Drugs that might affect esophageal motility were discontinued for 24 h before the study. The basal LES pressure was measured by the sleeve sensor in relation to the gastric pressure. Manometry was performed after a 4- to 6-h fast, and in smokers, after abstinence from smoking for at least 6 h. Lower esophageal sphincter pressures and TLESRs were measured with the patient in the supine position for 40 min followed by six water swallows. The duration of the total study was approximately 45 min.
The ambulatory Digitrapper (MK III, Synectics, Mississauga, Ontario, Canada) was used to perform 24-h pH testing. The pH probe was positioned 5 cm above the LES, as determined by manometry. Gastresophageal reflux was defined as a drop in esophageal pH less than 4, and the percentage of reflux in 24 h was calculated for each patient. All the patients were asked to stop antireflux medication for 5 days before 24-h pH testing.
All the patients underwent LNF, as previously described by Anvari and Allen  in 1999. The procedure was performed through five cannulae (two 10 mm and three 5 mm in diameter). The esophagus was mobilized for a distance of 4 to 5 cm, partially through the hiatus. The vagi were identified and protected. Minimal dissection was used behind the esophagus to create a window large enough to accommodate the fundic pull-through. Short gastric vessels were divided only as necessary to allow a loose wrap without placing tension on the spleen. The superior pole of the fundus was pulled behind the esophagus through the window created, and three interrupted 2-0 nonabsorbable sutures were used to fashion a standard Nissen fundoplication over a 42- to 52- Fr bougie. The sutures were positioned 1 to 1.25 cm apart, creating a 2- to 2.5-cm wrap, with the most superior suture incorporating a bite of the esophagus. The esophageal hiatus was repaired only if there was a hiatal hernia.
A water-soluble contrast swallow was performed on postoperative day 1 to check wrap integrity, rule out leakage, and assess esophageal clearance. The patients then were started on a fluid diet and if this was tolerated, discharged home on postoperative day 2. They were instructed to change their intake slowly to pureed, followed by normal food over the ensuing 3 weeks. They were allowed to resume full activity on discharge.
All the patients were invited to undergo 24-h pH testing, esophageal manometry, and symptom score evaluation 6 months after the operation, as is routine in our center. Endoscopy, gastric emptying, and barium studies were performed only when clinically indicated.
Symptom score evaluation
Symptom score evaluation was performed by an independent observer for all the patients preoperatively and 6 months postoperatively using a previously validated GERD symptom score . Six specific symptoms of GERD were scored as a product of severity (score range, 0–3) and frequency (score range, 0–4): heartburn, regurgitation, epigastric or chest pain, epigastric fullness, dysphagia, and cough (postprandial or in the supine position).
Basal end-expiratory LES pressure was referenced to intragastric pressure and determined by taking a visual mean at each minute of basal pressure recording. The mean value for 40 min was obtained for each patient. The completeness of the relaxation at the gastroesophageal junction during water swallows was determined by calculating the difference between the nadir pressure at relaxation and the intragastric pressure.
For preoperative studies, TLESR was defined as a sudden drop, lasting at least 5 s, in pressure at the gastroesophageal junction of more than 5 mmHg to within 2 mmHg of intragastric pressure [15, 18]. This could not be accompanied by a pharyngeal swallow signal within 5 s before onset until the relaxation was complete. For postoperative studies, transient LES relaxations were scored if the nadir pressure during relaxation was more than 50% of basal resting pressure, or if nadir pressure reached a level lower than 2 mmHg relative to intragastric pressure.
Statistical analysis was performed using Statview 4.5 (SAS Institute, Cary, NC, USA) for the MacIntosh. All values are expressed as mean ± standard error of the mean. Paired values were compared using Student’s t-test, and statistical significance was set at 0.05.
Preoperatively, the 73 patients had 174 episodes of TLESRs altogether (2.38 ± 0.32 per patient), with a nadir pressure less than 2 mmHg. The mean basal pressure for all the patients was 10.78 ± 0.62 mmHg, and the mean nadir pressure was 0.85 ± 0.14 mmHg. The percentage of acid reflux time in 24 h was 7.53 ± 0.82. The mean reflux symptom score was 38.71 ± 1.96. The mean dysphagia symptom score was 4.01 ± 0.54.
Outcome of surgery
All 73 patients underwent LNF, and the mean operative time of 48.56 ± 2.05 min. No intraoperative or postoperative complications were observed. The mean hospital stay was 2.95 ± 10.19 days. At 6 months postoperatively, the mean reflux symptom score fell to 16.80 ± 1.55 (p < 0.0001) (Fig. 1). This was confirmed by 24-h pH studies, which showed a drop in the mean percentage of acid reflux time to 1.08 ± 0.26 (p < 0.0001) (Fig. 2). There were no patients for whom the 24-h pH study showed abnormal results at 6 months. All the patients showed a significant increase in the basal LES pressure (mean, 19.18 ± 1.10 mmHg; p < 0.0001) and nadir LES pressure (mean, 6.23 ± 0.49 mmHg; p < 0.0001) (Fig. 3), and the mean dysphagia symptom score was 3.44 ± 0.46 (p = 0.17) (Fig. 4). Four patients continued to have dyspepsia despite their normal postoperative 24-h pH results. Their symptoms were well controlled by proton pump inhibitor therapy, either regular single daily doses or as required. These patients did not exhibit TLESR postoperatively.
Effect of surgery on TLESRs
The number of TLESRs also was reduced significantly to a mean number of 0.19 ± 0.07 per patient (p < 0.0001) (Fig. 5). A total of 14 TLESRs occurred in only 8 of 73 patients with a mean nadir pressure of 5 ± 1.07 mmHg. No TLESR episode was observed in which the nadir pressure dropped to less than 2 mmHg. After laparoscopic fundoplication 65 (89%) of the patients exhibited no TLESRs.
Transient lower esophageal sphincter relaxation is neurally mediated abrupt reduction in LES pressure. Current evidence indicates that TLESR is mediated primarily through vagal pathways. Gastric distension, cholecystokinin after meals, and pharyngeal intubation have been reported as stimulating factors. Suppressing factors include sleeping, anesthesia, stress, hiatal hernia, and recumbent posture [12, 19]. It is thought that TLESR accounts for most of the reflux episodes in normal subjects and more than half of the reflux episodes in patients with reflux disease [9, 20, 21]. Therefore, TLESR is an attractive target for pharmacotherapy. Several agents have been shown to reduce the rate of TLESR including cholecystokinin-A antagonists, anticholinergic agents, nitric oxide synthase inhibitors, morphine, somatostatin, serotonin type 3 receptor antagonists, and γ-aminobutyric acid-B agonists. Their predominant site of action appears to be on either the afferent pathway or the central integrative mechanisms within the dorsal vagal complex in the brain stem. Most of the agents tested are unsuitable for clinical use, either because of side effects or because an orally effective formulation is lacking . Omeprazole has been reported to have no effect on TLESR , whereas H2-blockers are thought to decrease their frequency . Open fundoplication in a small number of studied patients has been shown to reduce the frequency of TLESR [14, 16, 24]. The proposed mechanisms underlying these effects include the creation of an artificial high-pressure zone around the LES that persists during both transient and swallow-induced LES relaxation.
There has been a steady move in most centers toward performing the Nissen procedure laparoscopically. The LNF has resulted in reduced perioperative morbidity, shortened hospital stay, diminished postoperative discomfort, and earlier return to normal activities [2, 5, 7, 8, 11, 13, 15, 27]. In addition, LNF has proved to be a safe and effective alternative to open Nissen fundoplication, and has become the operation of choice for surgical treatment of GERD [4, 5, 7, 8, 11, 13, 15, 27]. It is used increasingly as an alternative to long-term proton pump inhibitor therapy . A significant increase in mean resting and nadir LES pressure [25, 26, 27] and augmentation of the length of the high-pressure zone exposed to the intraabdominal positive pressure all have been reported with LNF .
Our study confirmed earlier observation with respect to augmentation of basal and nadir LES pressures by laparoscopic fundoplication [2, 3]. The occurrence of TLESR was abolished in 89% of patients. In the remaining patients, the frequency of TLESR observed during a 40-min study was markedly reduced. The magnitude of reduction observed in our laparoscopic group (95%) was considerably higher than that reported in the open group (50%). The reason for the more pronounced effect is not clear. It may relate to differences in the method and period of observation. The patients in our study cohort received a relatively tight wrap (45–52 Fr), as compared with that in previously reported open series, as noted by higher LES resting and nadir pressures postoperatively. Despite this, the dysphagia symptom score was statistically no different from the preoperative value. No patient reported significant dysphagia, suggesting that a nadir pressure of 5 to 6 mmHg does not cause a significant sense of hindrance to the passage of food if esophageal motor function is relatively intact. The effect of these higher resting and nadir LES pressures on TLESR after LNF outcome has not been investigated.
The mechanism by which LNF inhibits the triggering of TLESR is not known, but may involve the buttressing effect of the fundal wrap on the distensibility of the gastric cardia, with blunting of distention-induced TLESR stimulation. Esophagogastric mobilization raises the possibility that this manipulation may affect the afferent arm of the TLESR reflex or reduce the total distensibility of the gastric fundus. There is evidence that reduction of acid exposure in the esophagus may have a role in decreasing TLESRs. This study also confirms previous reports that LNF renders swallowing-induced LES relaxation incomplete [14, 16, 22, 24]. This is presumably caused by mechanical compression of the distal high-pressure zone by the fundic wrap. However, despite this inadequate relaxation, no patient reported any significant dysphagia after the initial 3 to 6 weeks subsequent to surgery.
In summary, LNF reduces the incidence of TLESR even when increased basal and nadir LES pressures are taken into account, suggesting that additional mechanisms may be involved in this process. Further studies are necessary for an understand of the the mechanisms involved in this process.