Esophageal manometry performed with nonperfused catheter systems can confirm the initial presumptive diagnosis of achalasia made from clinical symptoms and radiographic findings.24 The classic features of achalasia on conventional esophageal manometry include: (1) aperistalsis in the smooth muscle segment of the esophagus, usually accompanied by low-amplitude contractions secondary to a dilated esophagus, (2) elevation of the LES resting pressure, and (3) incomplete relaxation of the sphincter after a wet swallow (Fig. 33-3). Often, the esophageal body resting pressure may be higher than the gastric pressure, as the elevated LES pressure prevents the intraluminal pressure from relaxing to the gastric baseline. Achalasia is classified as vigorous when the amplitude of the simultaneous contractions in the esophageal body is greater than the lower limit of normal (>30 mm Hg). The vigorous form may represent an earlier presentation of achalasia when some of the intramural ganglion cells are still present, and some prior studies suggested that the response to therapy may be better in this subgroup.25
Classic features of achalasia revealed on esophageal manometry (LES, lower esophageal sphincter; S, swallow).
High-resolution manometry (HRM) utilizes a larger number of pressure sensors spaced throughout the catheter than conventional manometry, providing enhanced details in the characterization of each swallow. Data from high-resolution esophageal manometry can be interpreted and displayed in color-coded plots called esophageal pressure tomography or Clouse Plot.26 With HRM, esophageal motility disorders can be categorized according to the Chicago Classification using several calculated parameters. Under this system, achalasia is defined by impaired GEJ deglutitive relaxation (normal: eSleeve 3-second nadir <15 mm Hg) and aperistalsis. It can be further classified into three subtypes (I, II, and III), distinguished by the esophageal body intraluminal pressure response with each swallow. Type I achalasia shows no change in esophageal body pressurization with swallowing, whereas type II achalasia results in panesophageal simultaneous pressurization (>30 mm Hg). Type III (spastic) achalasia is characterized by simultaneous, abnormal, lumen-obliterating contractions or spasm.27 Among the three subtypes, type II has been shown to be most responsive to therapy regardless of modality, and is an independent predictor of treatment success. On the other hand, type III achalasia has been associated with the lowest treatment response rate and is a negative predictor of treatment response.27
Endoscopy should be included in the evaluation of patients with a presumptive diagnosis of achalasia to examine the esophageal mucosa, GEJ, and cardia and fundus of the stomach. Inspection of the esophagus may demonstrate a dilated esophagus, whereas the esophageal mucosa may reveal signs of erythema and/or ulcerations secondary to stasis of food. Signs of esophageal candidiasis may also be present. The GEJ usually resists passage of the endoscope into the stomach. Inspection of the GEJ may reveal a tumor invading from either esophageal or gastric mucosa, indicating secondary or pseudoachalasia. The most common neoplasm is gastric adenocarcinoma. Other obstructive lesions leading to secondary achalasia should also be ruled out. Endoscopy also permits appropriate biopsy when necessary to rule out inflammatory or infectious complications or neoplasm.
The most important consideration in establishing the diagnosis of achalasia is differentiating primary achalasia from pseudoachalasia or secondary achalasia. The key historical points that raise suspicion for a malignant cause are short duration of symptoms (<6 months), advanced age at presentation (>60 years), and usually weight loss. Significant resistance is usually encountered when attempting to pass the endoscope through the GEJ. Esophageal manometry generally is not useful for distinguishing between primary and secondary achalasia. We recommend that patients undergo CT scan of the chest and abdomen to determine if there is an infiltrating lesion of the mediastinum or gastric cardia or fundus.
If endoscopic biopsy is unrevealing, endoscopic ultrasound with fine-needle aspiration may be helpful. Common benign conditions that mimic achalasia include (1) stricture of the distal esophagus with esophageal dilatation in scleroderma from collagen infiltration of the submucosal layers and (2) stricture of the distal esophagus from chronic gastroesophageal reflux disease resulting in dilatation of the esophagus. Fortunately, these disease entities can be differentiated from achalasia by manometry and endoscopic evaluation.
Chagas disease presents similarly to idiopathic achalasia in terms of manometric and endoscopic findings. This disease is endemic in regions of Central and South America and is caused by the parasite Trypanosoma cruzi. Evidence to raise suspicion for this diagnosis can be elicited from the history.
The pathogenesis of achalasia involves the degeneration of ganglion cells in the myenteric plexus of the esophagus with a predilection for the abnormality to be present in the region of the LES. Treatment is targeted toward decreasing LES pressure to ease the passage of food into the stomach. There is no treatment that can restore peristalsis in the body of the esophagus. Therapy for achalasia includes medical treatment, pneumatic dilation, botulinum toxin injection, and surgery28 (see Table 33-1; see also Chapters 33-35).
The goal of medical therapy is to promote relaxation of the LES through the use of appropriate pharmacologic agents. Unfortunately, none of the medications currently available provide sustained relief of symptoms. Calcium channel blockers and nitrates can relax the smooth muscles of the LES. The best results have been achieved with sublingual isosorbide dinitrate, which relaxes the LES rapidly and has sustained effects for at least 1 hour. Patients use sublingual isosorbide dinitrate just before a meal at a usual dose of 5 or 10 mg. Studies demonstrate a significant decrease in dysphagia for most patients taking this drug; however, often they cannot tolerate the headaches precipitated by the treatment. Decreasing effectiveness of the drug over time is also frequently noted.
A number of calcium channel blockers have been studied in patients with achalasia, including diltiazem, nifedipine, and verapamil. Nifedipine is the most extensively studied. A dose of 10 or 20 mg sublingually 30 minutes before eating demonstrates a decrease in both the LES pressure and symptoms of dysphagia. Oral diltiazem and verapamil have been shown to decrease LES pressure, but the symptomatic benefit is more variable. Oral verapamil can achieve adequate blood levels in achalasia despite the decrease in esophageal transit time and emptying. Unfortunately, studies have not demonstrated a consistent clinical benefit with calcium channel blockers, and their use is also limited by tachyphylaxis and other side effects, most notably headaches and hypotension.29
In light of the limited benefits, medical therapy is reserved for patients who cannot or will not consider more aggressive therapy.
Rubber bougie: Mercury-filled rubber bougies have been used to dilate the LES as a temporal measure for treating patients with achalasia, using a 50 to 60F bougie for the initial dilatation. Despite some data purporting a several-month benefit in reducing dysphagia, it is apparent that this method has limited value. Many patients report that the dysphagia is decreased, but the effect is very short-lived.
Pneumatic dilation: Pneumatic dilation of the LES is the nonsurgical treatment of choice for achalasia. Balloons of various sizes have been used, with the primary purpose of weakening the LES by tearing the muscle fibers. Older dilators were made of cloth (e.g., Brown-McHardy dilators), but these are no longer manufactured. The Rigiflex dilator is the current model. The dilator is passed over a guidewire with fluoroscopic guidance, and a Witzel balloon is passed through the endoscope and inflated under direct visualization.30 Many methods have been developed for balloon dilation, with variables including balloon size (diameter range 2.5–5.0 cm), number of inflations, and amount of time the balloon remains deployed. Regardless of technique, the results are similar. A good-to-excellent result lies in the range of 60% to 85% dilation depending on the study cited. Approximately two-thirds of patients have good-to-excellent results after one or more dilations for a median follow-up of 11 years. Most prospective studies suggest that approximately 50% of patients will require a second dilation within 5 years.31 In direct comparison between pneumatic dilation and surgical myotomy, the success rates between the two treatment modalities appear to be similar.
Prior studies have suggested young age, postdilation LES pressure greater than 20 mm Hg, and the use of smaller balloons to be negative predictors for sustained treatment response from pneumatic dilation. On the other hand, the emptying time of barium from the esophagus after dilation appears to be the best indicator for a sustained benefit.32 If barium emptying time is prompt on examination 3 months after pneumatic dilation, most patients will experience a sustained benefit over the next several years. If pneumatic dilation is repeated for a second time and prompt emptying of barium from the esophagus is not observed, surgical correction with myotomy would be recommended (described in Chapters 34 and 35).
Although it is the current nonsurgical procedure of choice, pneumatic dilation is not performed without risk. The rate of perforation associated with this procedure ranges from 2% to 6%. Most of the perforations occur on the left side. Therefore, a modified barium swallow with Gastrografin is recommended routinely after dilation to rule out perforation. Fortunately, mortality associated with perforation is rare (<0.2%). When an obvious perforation is diagnosed, immediate surgical repair is undertaken. If Gastrografin swallow or CT scan fails to reveal an obvious perforation but the patient continues to have chest pain and fever, he or she should be kept at nothing by mouth and given a course of antibiotics, with repeat barium swallow (with or without a CT scan) to confirm resolution.
Given its success rate and less invasive nature, endoscopic pneumatic dilation has been compared to surgical myotomy for treatment outcome. The most recent prospective trial in Europe randomizing 201 achalasia patients to pneumatic dilation versus laparoscopic Hellar myotomy found no significant difference between the two groups with regard to all parameters of treatment response, including symptoms, LES pressure, esophageal emptying, quality of life, and esophageal acid exposure.33 As patients in this study were only followed for a mean of 43 months, further studies are needed to compare the longer-term outcomes between the two therapies.
Botulinum (Botox) Injection
Botulinum toxin inhibits release of acetylcholine from neurons. It has been theorized that endoscopic injection of botulinum toxin in the anatomic area of the LES would inhibit the release of acetylcholine in neurons that play a role in LES smooth muscle tone, thereby decreasing LES pressure. Several small studies have demonstrated the benefit of endoscopic botulinum toxin injection. Unfortunately, although these initial studies demonstrated up to 90% immediate symptomatic relief, the benefit was relatively short-lived. Subsequent studies showed the median duration of benefit to be only about 6 months. Approximately two-thirds of patients were asymptomatic at 6 months, with the remission rate further decreasing to 45% at 1 year. Botulinum toxin injection has also been found to be significantly more effective in patients over age 50 (80% vs. 40%).25 Even if a sustained result is not achieved, no data have demonstrated that toxin injection results in increased morbidity or worse outcomes if pneumatic dilation or surgery should follow. The drawback to using toxin injection is the high cost (approximately $300 for a vial of botulinum toxin). The advantage is its excellent safety profile. Fewer than 25% of patients receiving botulinum toxin injection experience transient mild chest pain, and fewer than 5% experience reflux symptoms.
Various treatments are available for achalasia. Medical therapy with nitrate and calcium channel blockers has a short-term, limited role. The effect of botulinum toxin injection, although safe, is relatively short-lived and may be most useful for older patients (age 50 and older), in whom the risk of pneumatic dilation or surgery is escalated. Pneumatic dilation for most patients is the first-line nonsurgical therapy, capable of yielding a sustainable benefit in 70% of patients. When dilation fails, surgical myotomy is the treatment of choice.