285
35
Botox, Balloon, or Myotomy:
Optimal Treatment for Achalasia
Lee L. Swanstrom and Michelle D. Taylor
balloon to achieve disruption of the circular fi bers of the LES.
• Myotomy: Surgical division of all muscle layers of the lower esophageal sphincter mechanism, extending from the dilated portion of the esophageal body well onto the anterior gastric wall to insure complete disruption of the con- tractile mechanism.
35.1. Data Review
This review will cover four main controversies:
• Balloon dilatation vs. myotomy as initial treatment.
• The role of Botox in the treatment of achalasia.
• The superiority of open or laparoscopic myotomy.
• Should minimally invasive myotomy be per- formed through the chest or the abdomen?
While other controversies still exist regard- ing achalasia treatment, for the sake of this review, several controversies will be considered resolved, including: the size and type of dilating balloon (large and rigid), the role of medical therapy (only for symptomatic spasm), the treat- ment of failed myotomy or dilatation (repeat myotomy or esophagectomy), the extent of the myotomy (long), and the best treatment for mega or sigmoid esophagus (myotomy or esophagectomy).
Achalasia is a primary and profound esophageal motility disorder with an unclear etiology and which is, to date, incurable. In spite of its rare occurrence in the population (1:100,000), it stimulates large amounts of research and commentary by gastrointestinal (GI) physicians and surgeons, in large part due to ongoing controversy over the optimal treatment of these patients. When analyzing treatment options it is critical to keep in mind that all treatments are palliative in nature and are primarily aimed at relief of dysphagia and regurgita- tion. Normal esophageal function is almost never restored, and even a patient with an excellent result will not have completely normal swallowing.
Defi nitions: For the purpose of this review the terms used are defi ned as follows:
• Achalasia: A primary motility disorder of the esophagus characterized by complete absence of antegrade peristalsis in the smooth muscle body; either due to total noncontractility or simultaneous contraction (vigorous achalasia) and by abnormalities in the receptive relax- ation function of the lower esophageal sphinc- ter (LES).
• Botox: Flexible endoscopic injection of purifi ed Botulinum toxin (a potent neurotoxin) into the musculature of the LES. Typically 100 units of the toxin are injected into at least four quad- rants of the sphincter.
• Balloon dilation: Rapid dilation of the LES, usually under fl uoroscopic or endoscopic visu- alization, with a large-caliber (3 or 4 cm) rigid
35.2. Balloon Dilation, Botox, or Myotomy as Initial Treatment
This question has defi nite clinical impact as it effectively determines which specialty should primarily treat the achalasia patient. The out- comes to be considered are not only effi cacy of the intervention but also relative morbidities and cost effectiveness. Supporting data ranges from a few level 1 randomized, prospective trials to level 5 data based on opinion or animal models.
Numbers in clinical studies are small because of the relative rarity of achalasia and pooled data (level of evidence 3) provides the best generaliz- able data. Where possible, studies using large diameter balloon (vs. small balloon or rigid dila- tors) dilatation and laparoscopic/thoracoscopic (vs. open) myotomy were used.
Botox injection is an easy-to-administer out- patient treatment with a good safety profi le.
Early dysphagia relief is achieved in up to 66%
of cases.1 Level 1 evidence would indicate that even these good early results are poorer than those seen with surgical intervention. Zaninotto and colleagues have reported a prospective, randomized trial comparing Botox injection with laparoscopic myotomy in 80 patients. At 12-month follow-up, these comparable groups showed an 88% rate of dysphagia relief with surgery versus a 60% rate with Botox2 (Figure 35.1). Objective follow-up (pH and motility) was the same at 6 months.
The neurotoxicity of Botulinum toxin is a tran- sient phenomenon and there is a progressive failure rate with time. This is confi rmed by the long-term results of the randomized, controlled trial (RCT) by Costantini and colleagues (level of evidence 1) showing a 65% rate of dysphagia at
2-year follow-up versus an 18% rate with laparo- scopic myotomy and fundoplication.3 Case series reports also indicate that this failure is progres- sive with time and that eventually almost all patients will have recurrent problems.4,5
Level 3 evidence also indicates that the best results postachalasia treatment result when the LES pressure falls beneath 10mmHg.6 Follow-up testing in cohort series also indicates that Botox does not decrease sphincter pressures signifi - cantly2,7 and this leaves concern that the Botox- treated esophagus will have progressive dilation with time rather than the decrease in diameter seen after successful surgery.8 Finally, other evi- dence (level of evidence 3–5) supports the concept that defi nitive treatment (myotomy) is more dif- fi cult and subjects the patient to a higher perfora- tion rate following Botox treatment, although the end result appears to be the same.9,10
We conclude that surgical myotomy is superior to initial treatment with Botox for management of achalasia.
FIGURE 35.1. Outcomes of a randomized, prospective trial comparing Botox to Heller myotomy for achalasia.2
Surgical myotomy is superior to initial treat- ment with Botox for management of achalasia (level of evidence 1; recommendation grade A).
Balloon dilation and surgical myotomy are both longstanding and effective treatments for achalasia. Because they are typically used by dif- ferent specialties, comparative studies are rare.
The literature has a single published RCT that offers a direct, prospective comparison.11 This 1989 study had 81 patients who were well matched and randomized to dilation with a 3-cm balloon versus a Heller myotomy (with no fundoplica- tion) done by thoracotomy. The surgery patients had 95% near complete symptom relief compared to 51% with dilation at 5-year follow-up. The morbidity was higher in the balloon group as well, primarily a 5.4% incidence of esophageal perforation. Repeat dilation was performed in 16% of the patients.
More recent comparative case series (level of evidence 3–4) also support the effi cacy of myotomy over balloon dilation. Patti and cowork- ers present a nonrandomized, retrospective study comparing outcomes between large-caliber balloon dilation (19 patients) and a thoracoscopic
myotomy (30 patients). In this study, the long- term outcomes were markedly better for the tho- racoscopic approach (87% relief of dysphagia vs.
26%).12 Another retrospective study looked at the outcomes of 61 patients after balloon dilation with a crossover strategy of surgical myotomy in case of treatment failure. The study had a rather high perforation rate of 14% with another 14% of patients having no improvement in dysphagia after dilation. Both of these groups were treated with a surgical myotomy. On long-term follow-up (mean 5 years), this intervention cohort had a 61% failure rate following successful dilation and a 7% failure rate after myotomy. This particular study, although a level 2 prospective cohort study, has been criticized for its high perforation and failure rate in the dilatation arm.13
Finally, the relative effectiveness of Botox, balloon, or laparoscopic myotomy as initial treat- ment strategies for achalasia were compared using a Markov modeling strategy (level of evi- dence 3).14 One of the conclusions of this analysis was that Botox had the lowest effi cacy as an initial treatment in elective cases [quality- adjusted life-years (QALY) = 7.33]. Both dilation and laparoscopic myotomy were comparable and acceptable initial treatments (QALY = 7.40 for dilation and 7.41 for myotomy) as long as the perforation rate of balloon dilation was less than 3.8% and the success rate was at least 90%, while the mortality and failure rate of myotomy were less than 7% and 10%, respectively (Figure 35.2) Repeat dilations, however, were not indi- cated in this analysis, and patients who failed their fi rst dilation should be offered laparoscopic surgery.
We conclude that surgical myotomy is superior to balloon dilation for the initial management of achalasia.
FIGURE 35.2. Results of Markov modeling of initial treatment strategies for achalasia. One-way sensitivity analysis shows that laparoscopic Heller myotomy with partial fundoplication is the
Surgical myotomy is superior to balloon dila- tion for the initial management of achalasia (level of evidence 1 to 3; recommendation grade B).
Laparoscopic myotomy was fi rst described in 199115 and since then has become progressively more popular. It now is performed more often than open procedures done either through the chest or the abdomen. While this is true for many procedures now done laparoscopically, it doesn’t necessarily follow that the laparoscopic approach is superior. However, in the case of open versus laparoscopic myotomy, there is at least level 2 to 3 evidence to support the superiority of the less invasive approach. Table 35.1 summarizes the outcomes of these various studies. Overall, the studies reported similar outcomes. In all four studies described, it should be noted that the dys- phagia outcomes and postoperative refl ux com- plaints were universally similar or slightly better for the laparoscopic groups. Likewise, operative complications were the same for laparoscopic and open approaches, but blood loss and hospital stay were markedly less for the laparoscopic approach. A uniform negative for the laparo- scopic cohorts was a signifi cantly increased oper- ative time, but this was counterbalanced by a more rapid return to normal activity in the one study that recorded this parameter.16 It is unfor- tunate that there are no randomized, prospective comparisons between laparoscopic and open
87.0% 90.2% 93.5% 96.8% 100%
Laparoscopic Heller myotomy partial fundoplication Pneumatic dilatation
Botulinum toxin injection Thoracoscopic Heller myotomy
7.15 7.19 7.23 7.28
QALY
7.32 7.36 7.40 7.44 7.48
most effective treatment as long as the success rate for dysphagia relief is greater than 89.7%.14
myotomy, but at this point it is unlikely that there ever will be. However, the strong, consistent and statistically signifi cant outcomes in nonrandom- ized studies, as well as the factor of patient demand, defi ne the minimally invasive approach to myotomy as the gold standard. We conclude that laparoscopic myotomy is superior to open myotomy for surgical management of achalasia.
performing a myotomy with the perpendicular approach provided by thoracoscopic access.17 While this report described an 82% rate of good- to-excellent dysphagia relief (level of evidence 3), follow-up was quite short and a subsequent report in 1995 indicated a 60% incidence of signifi cant acid refl ux on pH study in 60% of the thoraco- scopic patients even though only one of six of these patients was symptomatic.18 In 1998 the same authors performed a case-matched analysis of the two groups and found that the laparoscopic approach was superior to the thoracoscopic in most parameters [length of stay (LOS) and post- operative refl ux rates in particular]19 (Table 35.2).
One retrospective study, which had 88 laparo- scopic repairs with fundoplications compared to 14 thoracoscopic with no fundoplication, found no signifi cant difference between the two approaches although there was a trend towards lower complications and faster recovery with the laparoscopic approach.20 On the other hand, a similar retrospective (level of evidence 3) study comparing 16 thoracoscopic to 17 laparoscopic TABLE 35.1. Case comparisons between laparoscopic and open Heller myotomy.
Excellent/good
result % Patient Operation Blood
Author Study type Number (dysphagia) Reflux % satisfaction time (min) loss (cc) LOS days Ancona21 Retrospective 17 open 100 6 – 125 – 10
case-matched 17 laparoscopic 94 0 – 178 – 4 Collard22 Retrospective 8 open 75 10 – – –
series 12 laparoscopic 84 0 – – – comparison
Dempsey16 Retrospective 10 open 90 40 80 122 220 8.8 case-matched 12 laparoscopic 92 25 84 137 50 2.7 Douard23 Prospective 30 open 93 7 83 120 120 7.5 series 52 laparoscopic 92 10 83 145 145 4 nonrandomized
TABLE 35.2. Results of a case-matched comparison of laparo- scopic and thoracoscopic Heller myotomy.
30 THM vs. 30 LHM (+Dor)a
– LOS THM = 6 days LHM = 3.5 days – Dysphagia THM = 13% LHM = 10%
– Reflux (pH) THM = 60% LHM = 10%
Abbreviations: LHM, laproscopic Heller myotomy; THM, thorascopic Heller myotomy.
aCase matched.
Source: Patti et al.19
Laparoscopic myotomy is superior to open myotomy for surgical management of achala- sia (level of evidence 2 to 3; recommendation grade B).
There is no level 1 evidence, but level 3 to 5 data strongly supports the superiority of laparoscopic over thoracoscopic esophageal myotomy for achalasia. Because open myotomy was frequently done via thoracotomy, it is not surprising that the fi rst reports of a minimally invasive treatment replicated this approach. The thoracoscopic approach quickly lost favor, partly because of its technical diffi culty, complex anesthesia require- ments, and, most importantly, because of its poor results in most series. One of the fi rst reports describing a minimally invasive approach for esophageal myotomy was the 1992 report by Pellegrini and associates, which described early results for 17 thoracoscopic myotomies and 2 laparoscopic myotomies. This report mentions the technical diffi culties involved, including the diffi culty in accessing the anterior gastric wall through the hiatus and the awkwardness of
myotomies with partial fundoplications showed uniform superiority of the laparoscopic approach (Table 35.3).24 We conclude that laparoscopic myotomy is superior to thoracoscopic or trans- thoracic approaches for surgical management of achalasia.
defi nite treatment in the form of a surgical myotomy. Its use is probably driven mostly by its ease of application, good safety profi le, and immediate gratifi cation factor.1
35.4. Current Practice
Clinical practice will often ignore the facts as presented in the medical literature, either from ignorance, because it goes against the practitio- ner’s training, institutional bias, or for fi nancial reasons. In the case of achalasia, it would seem that the majority of institutions treat patients more or less in line with the weight of the scien- tifi c evidence. Our current practice is to establish the diagnosis of achalasia with a barium swallow and esophageal manometry in all cases. The patient must have an upper endoscopy to exclude pseudoachalasia as a cause for symptoms or other fi ndings. In cases where the patient presents with nutritional compromise and near or complete esophageal outlet obstruction, treatment with Botox injection and small-caliber balloon dila- tion is done to temporize until more defi nitive treatment can be arranged. Repeat Botox injec- tions are never offered unless the patient is too morbid for any other care.
Patients are not typically risk stratifi ed for treatment otherwise, as the morbidity and mor- tality of either balloon dilation or laparoscopic myotomy are equal. Patients are counseled about their disease and the need for lifelong follow-up after any treatment. They are given the choice of either balloon dilation or a laparoscopic myotomy with the benefi ts and drawbacks of each being carefully defi ned. Balloon treatment is described as convenient, safe (<0.1% morbidity, 5% perfora- tion rate, and a 2% emergency intervention
35.3. Clinical Implications
Because of the relative rarity of the disease and the fact that achalasia patients are seen by both gastroenterologists and surgeons, many ques- tions regarding the treatment of achalasia remain only partially answered. On the other hand, the clinical realities of achalasia practice are obvious:
laparoscopic myotomy is the current gold stan- dard for treatment. Transthoracic approaches, in spite of their primacy in the past, simply do not work as well as laparoscopic myotomy. This is particularly true of thoracoscopic approaches, which have been calculated to be the least cost- effective treatment available.14 In most institu- tions, balloon dilation, though not a bad treatment, has been largely abandoned. This is due partly to the excellent effi cacy of laparoscopic myotomy (89%–98% good-to-excellent results) but perhaps even more to the risk aversion of gastroenterologists who are reluctant to deal with the 2% to 6% perforation rate of most series.
Botox, on the other hand, remains sporadically popular and still fairly widely practiced. This is in spite of its poor long-term success, low cost effectiveness, and risk of creating problems for
Laparoscopic myotomy is superior to thoraco- scopic or transthoracic approaches for surgi- cal management of achalasia (evidence level 3 to 5; recommendation grade C).
TABLE 35.3. Retrospective comparison of the results of laparoscopic myotomy and partial fundoplication compared to thoracoscopic myotomy without a wrap.24
Reduction Late Final LES LES diameter
Operative dysphagia pressure at 2-year
time (min) LOS (days) (%) Reflux (%) (mmHg) follow-up (%) Thoracoscopic myotomy 222 2 37.5 25 15.3 27
Laparoscopic Myotomy 148 5 5 10 10.4 50 + Dor p = 0.0001 p = 0.0001 p = 0.01 p = 0.0001 p = 0.0001 p = 0.0001
incidence), and relatively effective (around a 65%
initial relief or dramatic improvement in dyspha- gia). It is mentioned that around 20% of patients will subsequently require medication for acid refl ux and that there is a progressive failure rate over the fi rst 5 years, with only 30% to 40% of patients free from dysphagia at 5 years. Laparo- scopic myotomy is described as highly effective (88%–92% relief of dysphagia over 3 years), but we stress that it requires a true operation includ- ing a general anesthetic and a 24- to 48-hours hospital stay. With the addition of a partial fun- doplication, acid refl ux rates are described as being between 10% and 15%. Mortality rates are also quoted as 0.1% and acute reinterventions as being necessary 2% of the time. In our experi- ence, even though the dilations and myotomies are done by the same team, 90% of patients decide on the surgical myotomy – most often saying that the higher initial success rate is their primary consideration and the fear of perforation the next concern.
All myotomies are done laparoscopically unless the patient has a hostile abdomen and all are accompanied by a partial wrap if at all possible.
We will attempt a laparoscopic myotomy on a massively dilated or sigmoid esophagus but do cite a higher failure rate in such a case. Failure of a myotomy is treated with a balloon dilation and, if that fails, by a second laparoscopic myotomy without a fundoplication. Second failures, or fail- ures with mega-esophagus, are encouraged to consider a minimally invasive esophagectomy.
After therapy, patients are sent home on a pureed diet for 2 weeks. All patients are requested to undergo repeat manometry and a 24-hour pH test. Decision to place the patient on acid-sup- pressive medication is only based on the result of the postoperative testing as we have found symp- toms after surgery to have almost no correlation with objective fi ndings. Upper endoscopy is per- formed every 5 years for the slightly increased risk of malignancy due to the stasis.
34.5. Conclusion
The relative rarity of achalasia and its poorly understood etiology means that there is a relative lack of high-quality literature to base treatment
recommendations on. This is further compli- cated by the fact that there are three fairly good therapies for this incurable disease and that it is rare for a single practitioner to offer all three.
In actuality, there is undoubtedly a place for all three in a comprehensive treatment algorithm, and it is hoped that initial treatment will be based on medical evidence and not expedience or per- sonal bias.
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