Should low esophageal pH after myotomy be unequivocally interpreted as gastroesophageal reflux?
P.F. Crookes (Los Angeles)
It is widely recognized that Heller myotomy may result in postoperative gastroesophageal reflux (GER). Quite how frequent is difficult to determine from the literature, because of differing criteria used to assess reflux. In the much quoted review by Andreollo and Earlam published in 1987, no study using 24-hour esophageal pH monitoring had been reported at that time [1]. Rather, the incidence of postoperative GER was inferred from endoscopy or barium studies in patients complaining of heartburn, or who were found to have a postoperative stricture. From these data it was concluded that limited myotomy when performed transthoracically carried an incidence of GER of 7%, after transabdominal myotomy alone it was 14%, and after transabdominal myotomy combined with an antireflux procedure it was 7%. In the intervening years, many reports have included postoperative 24-hour pH measurements on a proportion of their patients. Most have assumed that a positive pH test is indicative of GER. This is not so.
Food fermentation and the development of low intraesophageal pH
A study by Smart et al. in 1987, although specifically related to patients undergoing dilation, identified a mechanism whereby a low pH was produced in the esophagus by fermentation of food residues, with the production of lactic acid [2]. This paper therefore postulated a mechanism of esophageal acidification which did not involve reflux of gastric acid. However, it was not possible to exclude the possibility that small amounts of gastric acid had slowly permeated the food residue in the region of the pH probe and contributed to the drop in esophageal pH. Other studies of 24-hour esophageal pH in achalasia by Shoenut et al. found a positive 24-hour pH score in 10 patients, but they did not indicate if acidic foodstuffs were excluded from the diet, and their in vitro lactobacillus cultures did not reach pH 4 [3].
We recently performed in vitro testing to assess whether it was possible for samples of food mixed with saliva to generate a pH less than pH 4 [4]. The study was stimulated by the observation that in some achalasic patients with a positive pH score, the pH tracing showed a slow steady decline rather than a sequence of sudden sharp drops such as are typically found in gastroesophageal reflux disease (GERD).
A total of 22 healthy volunteers chewed up portions of bland food such as bread, muffins or Graham crackers, and expectorated the contents into a small plastic bag, which was then incubated with a combined glass pH electrode at 37 °C for 24 hours. The initial pH of the specimens was 6.9 (range 5.6-8.0) and fell to a median of 4.0 (range 3.7-5.8) during the 24-hour period. Seven of 22 specimens reached a pH below pH 4. It took a median of 6.5 hours to reach a pH of 4 (Figure 1).
A review of pH tracings in 20 preoperative patients with achalasia, and 12 patients after myotomy was then made. Five patients preoperatively demonstrated abnormal acid exposure on 24-hour pH monitoring, four of them showing the slow steady decline resembling the pH tracing of the in vitro studies (Figure 2). These patients all had retained food residues at endoscopy. One patient, who had a hiatal hernia and complained of hiccups, demonstrated numerous typical reflux episodes. Of the 12 postoperative studies, abnormal acid exposure was present in six, with three demonstrating a slow steady decline and three having typical sharp rapid drops suggesting true GER. Standard computerized analysis of these tracings does not distinguish the two patterns, despite the appearance being immediately obvious on inspection of the raw tracing.
Figure 1. pH tracing of food maintained at 37 °C over 24 hours, showing slow steady drop to just below pH 4.
Which pH threshold should be used?
The use of pH 4 as the cutoff point to determine when acid from the stomach has reached the esophagus is almost universal [5]. This particular threshold was chosen partly because it corresponded to the pH at which symptoms tended to be experienced by the patient, but also because above pH 4, pepsin is largely inactivated. In fact its activity in the range pH 3-4 is much less than in the range 2-3. Almost all workers define an abnormal pH test by reference to the length of time, or the pattern of exposure, spent below pH 4. In our studies of food fermentation, we found that in both the in vitro studies and the studies of patients demonstrating a slow steady downwards pH drift, that the nadir pH almost never fell below pH 3.6. This suggested the use of pH 3 as a simple objective discriminatory threshold. Normal values for the various parameters of the pH record are easily available for any pH threshold (Table I). In addition, clinical and experimental evidence suggest that esophageal mucosal damage from gastric juice in the range pH 3-4 is mild compared with that at pH below pH 3 [6, 7].
Figure 2. 24-hour pH tracing of a patient with achalasia showing slow steady drop after a meal and dipping below pH 4 for several hours.
All the patients in our series demonstrating sharp pH drops typical of reflux episodes were characterized by an abnormal percentage of the monitored period spent below pH 3 (Figure 3). We therefore propose that for computerized interpretation of esophageal pH tracings in patients with achalasia, a percentage time greater than 2.9% spent below pH 3 tends to indicate true reflux of gastric juice and effectively excludes food fermentation as the cause of an abnormal result on 24-hour esophageal pH monitoring using pH 4. This argument is strengthened by the fact that the lowest pH generated by food fermentation in vitro was pH 3.7. Using this criterion correctly identified the one preoperative patient and the three postoperative patients whose pH tracings visually demonstrated sudden sharp drops in pH typical of acid reflux (Figure 4). Clearly, the distinction can be immediately made by eyeballing the raw tracing, but it is likely that many surgeons in practice who request pH testing will have to send their patients to an esophageal laboratory in which they are not directly involved themselves, and have to rely on a printed summary report. Clinicians should be aware of the possibility that food fermentation may artefactually produce an abnormal pH score in a patient with achalasia, and if they are not provided with the raw tracing, reporting the presence or absence of abnormal pH below pH 3 will eliminate this as a source of confusion.
Figure 3. Preoperative patients with achalasia, in which only one of five with an abnormal score based on pH 4 demonstrated abnormal time below pH 3.
Figure 4. Postoperative patients with achalasia, showing six patients with an abnormal pH score based on pH 4: three have true reflux with abnormal time below pH 3.
What is the rate of severe esophagitis?
Differences in the reported frequency of post-myotomy esophagitis are often used as evidence to advance claims for the superiority of one technique over another. Surgeons continue to disagree as to whether the approach should be through the chest or abdomen, the extent of the myotomy down on to the stomach, whether or not an antireflux procedure should be added, and if so whether anterior (Dor) or posterior (Toupet). These issues are not yet settled. It is now emerging that the results of surgical treatment of achalasia differ from those of GERD in one important respect: they tend to deteriorate with time. Consequently, the newer procedures with the shortest follow-up times tend to have the most optimistic assessments. Several carefully followed-up series have demonstrated this tendency [8, 9]. This fact should be borne in mind in considering the reported results of differing surgical therapies.
A second factor to introduce confusion is the differing criteria for diagnosing esophagitis. In some reports it merely means that the patients complained of heartburn. In others, endoscopy was performed, and in others, only signs of stricture were regarded as evidence of reflux. Most patients, unless part of a controlled prospective study, are not offered endoscopy postoperatively unless they have significant symptoms. Even in carefully followed series such as the series of 100 consecutive patients reported by Csendes, only 32 patients had postoperative endoscopy [10].
The rate of severe esophagitis after Heller myotomy appears to depend on three surgical factors.
Extent of the myotomy below the true gastroesophageal junction
An isolated myotomy extending only a few millimeters onto the stomach tends to have a much lower incidence of esophagitis than when it extends more than 1cm. Carrying the myotomy onto the stomach for 2 cm gave 100% incidence of severe reflux [11]. By contrast, the more limited myotomy as practised by Ellis is associated with a low incidence of significant reflux (5%) [12].
That these excellent results are not uniformly achievable by other surgeons is demonstated by the higher incidence reported by others after isolated Heller myotomy [11, 13-15].
Addition of an antireflux procedure
The severe consequences of GER in an aperistaltic esophagus have led many surgeons to propose the simultaneous performance of an antireflux procedure, usually a modified Belsey, Toupet, or Dor type, at the time of myotomy. There is broad agreement that a Nissen fundoplication, while affording the best protection against reflux, adds too much outflow resistance and leads to esophageal failure in the long term [16]. Transthoracic myotomy is therefore accompanied by a modified Belsey or Dor procedure, and Toupet or Dor are used if the abdominal approach is employed. The incidence of moderate to severe esophagitis is variously reported from 2% (1 of 48 cases), for the Heller-Toupet operation, 9% for the Heller-Dor operation, and up to 14-33% in the Toronto series, depending on length of follow up [8, 17, 18].
Surgical approach and extent of mobilization
Closely related to these surgical issues are whether or not the incidence of postoperative reflux is related to a) the surgical approach (abdominal vs thoracic) and b) the extent of perihiatal dissection. It is generally believed that the abdominal route carries a greater tendency to postoperative reflux, partly because it involves a more extensive mobilization of the esophagus from its perihiatal attachments. In the collective review by Andreollo and Earlam, the overall incidence of reflux after abdominal myotomy was about twice that following isolated transthoracic myotomy, a proportion shared by studies which included both approaches [1, 15].
Reflux after minimally invasive myotomy
The advent of minimally invasive myotomy, either thoracoscopic or laparoscopic, has prompted a re-evaluation of the approach of Ellis. It is extremely difficult to perform an antireflux procedure thoracoscopically, and isolated myotomy has generally been advocated when using the thoracoscopic route. The laparoscopic approach readily lends itself to the performance of either Toupet or Dor type partial fundoplications. Preliminary experience of all three approaches had been published, but it is not yet possible to make a long-term assessment of the long-term incidence of esophagitis after minimally invasive myotomy [19-21].
References
12 Ellis FH. Oesophagomyotomy for achalasia: a 22 year experience. Br J Surg 1993;80:882-885.
13 Harley HRS. Achalasia of the cardia. Bristol: J. Wright and Sons, 1976.