Achalasia of the : A Surgical Disease

Valerie A Williams, MD, Jeffrey H Peters, MD, FACS

Achalasia is a primary esophageal motility disorder of un- signaling as it relates to the distal esophagus and LES in clear etiology. As treatment has evolved during the past 10 achalasia has been a subject of growing investigation. Nitric to 15 years, it has become primarily a surgical disease. It is oxide is thought to be the major inhibitory neurotransmit- uncommon, but not rare, affecting approximately 1 in ter controlling relaxation of esophageal .9,10 100,000 individuals per year.1 Occurring equally in men It has been suggested that nitronergic inhibitory and women, it is an acquired condition usually diagnosed are lost in greater proportion than cholinergic neurons dur- between 20 and 50 years of age, but can occur at any age. In ing the achalasia disease process.11 1672, Sir Thomas William first described the disease as Supporting this thesis, studies in knockout mice lacking “cardiospasm” and treated the problem with dilation using synthase (NOS) have found high LES resting a whale sponge attached to a whale bone. It was not until pressures and absent LES relaxation.12 In humans, speci- 1927, whenAFHurst determined that the problem was mens from achalasia patients have shown complete loss of the result of an inability of the lower esophageal sphincter NOS enteric neurons and NOS activity as compared with (LES) to relax, and named the disease achalasia, a Greek nonachalasia specimens.13 Bruley des Varannes and col- term meaning failure to relax.2 Normal individuals have a leagues14 recently reported a study suggesting a serum- lower esophageal high-pressure zone, which completely re- borne substance, supporting an immunologic mechanism. laxes with initiation of a swallow. In achalasia, residual Gastric fundic muscle from normal humans was cultured pressures in the LES remain well above normal after swal- with serum from achalasia patients, gastroesophageal reflux lowing, resulting in a functional outflow obstruction at the disease patients, or normal subjects. The normal fundus gastroesophageal junction. In addition, the LES can be incubated with serum from achalasia patients had a de- hypertensive, resulting in higher than normal resting pres- crease in NOS neurons as compared with controls. In ad- sures, and the esophageal body is aperistaltic, all leading to dition, relaxation of electrically stimulated circular muscle failure of bolus transport.3 When untreated, intraesopha- contractions was substantially decreased after incubation geal pressures rise and the esophagus slowly dilates, often to with serum from patients with achalasia. the point of gross deformity.4 The most common secondary cause of achalasia is Cha- gas’ disease15,16 a systemic disease caused by infestation by the protozoan Trypanosoma cruzi. Chagas is transmitted to ETIOLOGY humans by the reduviid or “kissing bug” and infects intra- Achalasia can be primary (idiopathic) or secondary. Pri- mural neurons, causing autonomic dysfunction. Chagas’ mary achalasia is thought to result from a complete loss or disease is common in South and Central America, and relative absence of inhibitory ganglion cells in the myen- worldwide is considered to be the most common cause of teric (Auerbach’s) plexus of the esophagus. This loss creates achalasia.15,16 Pseudoachalasia occurs through infiltration an imbalance between excitatory and inhibitory neurons of the LES by or by iatrogenic condition, such as a 5 causing failure of the LES to relax. Several studies have tight fundoplication or external appliance, such as a documented diminished numbers of myenteric ganglion in band.17,18 diseased esophageal specimens and demonstrated the pres- ence of lymphocytic infiltrate and collagen deposition PRESENTATION AND DIAGNOSIS 6-8 within ganglion. Given these findings, an infectious Achalasia is a slowly progressive disease. As a consequence, agent, such as a virus, and its subsequent immune response, patients often present late in the course of this disease, is thought to be the cause of the ganglion loss, but the exact when their symptoms and anatomic abnormalities have etiology remains unknown. and cell become prominent. Diagnosis earlier in the disease process is possible, given conscientious attention to patients’ Disclosure Information: Nothing to disclose. esophageal reports and a high degree of suspicion. Clinical Received March 31, 2008; Revised July 14, 2008; Accepted August 13, 2008. symptoms include slowly progressive for solids From the Department of Surgery, University of Rochester Medical Center, and liquids, regurgitation of bland undigested food, chest Rochester, NY. pain, and . Patients can also have a history sug- Correspondence address: Jeffrey H Peters, MD, Department of Surgery, Uni- versity of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY gestive of aspiration, including recurrent pneumonia or 14642. email: [email protected] chronic .

© 2008 by the American College of Surgeons ISSN 1072-7515/09/$36.00 Published by Elsevier Inc. 151 doi:10.1016/j.jamcollsurg.2008.08.027 152 Williams and Peters Achalasia of the Esophagus J Am Coll Surg

Abbreviations and Acronyms HRM ϭ high-resolution manometry LES ϭ lower esophageal sphincter NOS ϭ nitric oxide synthase

Of important note, patients with achalasia can present with heartburn and, as such, mimic the presentation of gastroesophageal reflux disease. Reviewing the symptoms of 67 patients with achalasia, Spechler and colleagues19 found that 32 (48%) reported heartburn. This fact, cou- pled with diagnostic challenges in patients with early acha- lasia, including presence of a normal-caliber esophagus and artifactual LES relaxation on manometry (caused by rela- tive movement of the catheter and sphincter), likely leads to a small but real number of patients with achalasia erro- neously diagnosed with gastroesophageal reflux disease and undergoing . In fact, it is not un- common for patients with achalasia to be treated with pro- ton pump inhibitors. The clinician should be aware of this possibility; a careful review of both the manometric study and video barium examination will almost always reveal the characteristics of achalasia. This occurs for several potential reasons. Physiologically, heartburn has been shown to be precipitated by esophageal distention.20 Different neural stimuli (luminal acid versus distention) can be interpreted by the brain as the same symptom. It has also been sug- gested that achalasia can develop in the setting of underly- ing gastroesophageal reflux disease. The retrospective symptom review referenced here showed that of those with ϭ Figure 1. Barium esophagogram in a patient with achalasia. Note heartburn, 47% (n 15) had heartburn before develop- the esophageal air-fluid level and characteristic “bird’s beak” nar- ment of dysphagia, which persisted once dysphagia devel- rowing created by a nonrelaxing lower esophageal sphincter. oped, and an additional 28% (n ϭ 9) had heartburn before development of dysphagia, which stopped after onset of particularly in early achalasia, with the radiologists’ focus dysphagia. Heartburn symptoms developed in the remain- on anatomic characteristics, such as dilation and empty- ing patients (25%) after onset of dysphagia. Interestingly, ing.21 Reviewing the symptoms and barium studies of 38 those patients reporting heartburn had considerably less patients with confirmed achalasia, Blam and colleagues21 LES resting pressures as compared with those without found a poor correlation between symptoms and barium heartburn symptoms. Both mechanisms are likely at play. study findings, which led to a diagnostic delay, particularly A simple chest radiograph can suggest the diagnosis in in patients who presented with atypical symptoms (ie, advanced cases by the absence of a gastric bubble and pres- heartburn, weight loss, cough, asthma). Atypical symp- ence of a dilated fluid-filled esophagus, generally seen as a toms were reported in 34% of patients and resulted in a right-sided posterior mediastinal shadow.4 Upper endos- median delay of 30 months before correct diagnosis, as copy should be performed in all patients to exclude ob- compared with 11 months in those who reported typical struction from tumor or stricture. Findings will commonly symptoms (dysphagia, , regurgitation). Careful include retention of saliva and undigested food associated examination of fluoroscopic or video images should be rou- with a dilated esophagus, but can be normal. A barium tinely done, which will almost always reveal a flaccid non- swallow is often diagnostic, showing a dilated aperistaltic peristaltic esophagus devoid of the usual “stripping” esophagus, presence of an air-fluid level, or a characteristic waves.22,23 “bird’s beak” appearance created by a nonrelaxing LES The gold standard for diagnosis of achalasia is esopha- (Fig. 1).4 Barium studies can be interpreted as “normal,” geal manometry, which is the most sensitive diagnostic test Vol. 208, No. 1, January 2009 Williams and Peters Achalasia of the Esophagus 153

Table 1. Manometric Characteristics of Achalasia Hypertensive lower esophageal sphincter resting pressure Incomplete or nonrelaxing lower esophageal sphincter Aperistalsis of the esophageal body Esophageal pressurization: elevated lower esophageal baseline pressure available.3,17 Manometry is especially helpful in establish- ing the diagnosis in patients who present in an early disease state when other diagnostic evaluations appear normal.3 There are four classic manometric characteristics (Table 1): hypertensive LES, present in approximately 50% of pa- tients; nonrelaxing LES; esophageal aperistalsis; and ele- vated lower esophageal baseline pressure. A subset of acha- lasia patients can have simultaneous contraction waves of variable amplitudes, consistent with preserved muscle function, this is termed vigorous achalasia.3 Examining the manometric tracings of 26 patients with achalasia, Shi and colleagues24 found residual LES relaxation pressure to be the most accurate diagnostic manometric criteria. Specifi- cally, a residual pressure of Ͼ12 mmHg had 92% sensitiv- Figure 2. Lower esophageal sphincter residual pressure measure- ity for the diagnosis of achalasia. Coupled with aperistalsis, ments of patient controls (n ϭ 43) and achalasics (n ϭ 58). Only a residual pressure of Ͼ10 mmHg had 100% sensitivity one achalasia patient had a residual pressure of Ͻ10 mmHg. Reprinted from: Hirano I, Tatum RP, Shi G, et al. Manometric het- and 100% positive predictive value for achalasia. Similarly, erogeneity in patients with idiopathic achalasia. in a later study by the same group, examination of 58 2001;120:789Ϫ798, with permission. achalasic manometric studies revealed only one variant pa- tient who had a residual pressure after swallow-induced of achalasia and assessment of treatment efficacy.26,27 Aperi- LES relaxation that was Ͻ10 (Fig. 2).25 stalsis is readily evident on HRM and the technique facil- Although traditionally, a nonrelaxing sphincter and itates assessment of sphincter relaxation, one of the most complete aperistalsis were thought to be universally re- difficult aspects of conventional manometry (Fig. 3). quired for diagnosis of achalasia (it is debated which of HRM is made possible by a solid-state catheter with 36 these might be the primary and most important feature), it circumferential sensors spaced at 1-cm intervals. Pressure is likely that some heterogeneity exists in the manometric measurements obtained from the sensors are plotted in findings in patients with all the clinical characteristics of reference to both space and time. The closely spaced pres- achalasia. Hirano and colleagues have recently emphasized sure transducers and interpolation of the data eliminate the this fact.25 They carefully analyzed the clinical history and movement artifacts, which confound standard manometric manometric recordings of 58 patients with achalasia and techniques. Data have shown that, in the absence of previ- 43 control subjects. , barium swallow, histopa- ous hiatal surgery, failure of the LES high-pressure zone to thology, and response to treatment were used to help estab- relax below 15 mmHg is highly specific and sensitive for lish the diagnosis in patients without classic manometric achalasia.27 The ability of MII to quantitate bolus transport findings. Although it was uncommon, four manometri- can prove to be useful in the postoperative assessment of cally distinct variants were seen, ie, high-amplitude non- patients with achalasia after laparoscopic myotomy, al- peristaltic esophageal body contractions, short segments of though few studies to date have investigated its benefit. aperistalsis, retained complete LES relaxation on swallow- ing, and nonswallow transient relaxation. These findings were seen in only 4 of 58 patients, the vast majority had TREATMENT classic manometric findings of achalasia. This study pro- Achalasia is an incurable disease and treatment is focused vides a strong argument that variations truly exist. The on relief of symptoms. The goal of both surgical and non- clinician should be aware of these possibilities when evalu- surgical treatment is to eliminate the outflow obstruction ating patients with dysphagia. afforded by a nonrelaxing sphincter, relieve dysphagia, and The introduction of high-resolution manometry maintain a barrier against gastroesophageal reflux when (HRM) and multichannel intraluminal impedance (MII) possible. Nonsurgical treatment includes calcium channel studies can improve the diagnostic manometric assessment blockers and , injection of (Botox; 154 Williams and Peters Achalasia of the Esophagus J Am Coll Surg

Flexible endoscopic treatment Endoscopic injection of Botox into the LES aims to block release of from cholinergic neurons in an ef- fort to lower both basal and residual LES pressures.31 This treatment is short-lived, rarely results in substantial re- duction in LES pressure, and, although dysphagia can be improved, often requires repeat injections for continued relief. In a prospective randomized controlled trial com- paring Botox injection (n ϭ 40) with laparoscopic my- otomy and partial fundoplication (n ϭ 40), Zaninotto and colleagues32 found that although patients in both groups showed initial improvement in symptoms, 6 months after treatment dysphagia and regurgitation re- curred in nearly half (45%) of those treated with Botox. In addition, they determined that the probability of be- ing symptom-free at 2 years was considerably higher after myotomy (87.5%) than after Botox injection (34%). It is now recognized that Botox injection creates an inflammatory reaction in the distal esophagus with conse- quent submucosal , which can make subsequent surgical myotomy more difficult.33 Although commonly tried as a short-term treatment option, the authors believe Botox should be reserved for those who are not surgical candidates or abandoned altogether. Figure 3. High-resolution manometric study in (A) a normal sub- Pneumatic balloon dilation decreases esophageal out- ject and (B) a patient with achalasia. The lack of propulsive wave flow resistance by forceful “tearing” of the LES muscle fi- progression and the failure of the lower pressure band represent- bers. Protocols vary among clinicians when performing ing the lower esophageal sphincter can be clearly seen in (B) pneumatic dilation. In general, graded balloon dilation is compared with (A). begun using a 30-mm balloon as the initial dilator.34 The balloon dilator is passed into the esophagus and placed at Allergan) into the LES, and large-caliber (30 to 40 mm) the gastroesophageal junction by using or di- pneumatic dilation of the LES. Surgical treatment includes rect endoscopic vision. A Gastrografin esophagram fol- division of the muscle fibers of the LES and proximal stom- lowed by a barium swallow is performed after pneumatic ach. Although pharmacologic treatments such as calcium dilation to exclude esophageal perforation. Repeat balloon channel blockers, nitrates, and sildenafil have been shown dilation can be performed using progressively larger dilator to have physiologic effects on esophageal function, they sizes to 35 mm and 40 mm. The most common balloon rarely result in meaningful clinical improvement. With the dilators in current use are the Rigiflex and Witzel polyeth- advent of minimally invasive surgery, laparoscopic myot- ylene balloons. Rigiflex is a balloon on a catheter, which is omy has slowly shifted treatment of achalasia toward the placed using fluoroscopy, and the Witzel balloon is inserted greater use of surgical therapy. while attached to the endoscope. Risk of perforation using the Rigiflex is about 3% and that of the Witzel is 6%.35 Pharmacologic treatment Comparing pneumatic balloon dilation with Botox in- Pharmacologic treatments of achalasia, such as oral nitrates jection in a randomized trial, Cleveland Clinic investiga- and calcium channel blockers, act to inhibit intramural tors found that 70% (14 of 20) of patients who underwent neurons.These drugs attempt to recreate a balance between dilation were in symptomatic remission at 1 year as com- stimulatory and inhibitory nerve fibers to decrease the rest- pared with 32% (7 of 22) of patients who underwent Botox ing and residual pressure of the LES.Their effect is sporadic treatment.36 In addition, they found that balloon dilation and has shown only short-term success.28-30 In light of their resulted in substantial improvements in LES pressure, poor outcomes and potentially harmful systemic effects, esophageal barium column height, and esophageal diame- these agents are largely unreliable and unrealistic modali- ter, and Botox injection failed to show any change in these ties for longterm symptom relief. parameters. Similarly, when comparing pneumatic balloon Vol. 208, No. 1, January 2009 Williams and Peters Achalasia of the Esophagus 155 dilation with Botox injection in a double-blinded random- Swedish prospective randomized study of 51 patients com- ized study, Bansal and colleagues37 found that 89% (16 of paring pneumatic dilation (n ϭ 26) with laparoscopic my- 18) of patients who underwent balloon dilation had a de- otomy (n ϭ 25). A predefined dilation protocol was used, crease in their symptom grade as compared with only 38% beginning with a 30-mm (women) or 35-mm (men) Rigi- (6 of 16) of patients who underwent Botox injection. Most flex balloon and progressing as needed to 40 mm in those recently, a meta-analysis evaluating pneumatic balloon di- with persistent dysphagia at 7- to 10-day intervals.The lack lation and Botox injection for treatment of achalasia re- of such a protocol was one of the major criticisms of the ported that, although short-term failure rates were similar study performed by Csendes and colleagues.41 Laparo- between the two techniques, longterm (Ͼ6 months) results scopic myotomy was performed by experienced surgeons showed considerably less failures after dilation as compared using intraoperative endoscopy and Toupet posterior with Botox.38 hemifundoplication. Outcomes were assessed at 1 year af- In an analysis evaluating the longterm efficacy of pneu- ter treatment. Failure was defined as incomplete symptom matic dilation for achalasia, Katz and colleagues39 retro- control or symptom relapse requiring more than three spectively evaluated 72 patients at a mean of 6.5 years after treatments during the 12-month period, serious complica- dilation. Defined as no additional therapy needed for acha- tions or side effects, or patient request for alternative treat- lasia, success was seen in 85% of patients. Four patients ment. Esophageal perforation occurred in two patients in required additional pneumatic dilation. the dilation group (7.6%). All surgical procedures were More recently, Zerbib and colleagues40 retrospectively completed laparoscopically with no substantial periopera- evaluated longterm remission rates of pneumatic dilation tive morbidity. Treatment failure was significantly more for 150 patients with achalasia, using a fastidious dilation common in the dilation group (1 of 25 [4%] versus 6 of 26 [23%]; p ϭ 0.04). Mean symptom score after operation protocol that included several dilation sessions until devel- Ͼ opment of remission and close followup with fairly liberal was 11.3 and after dilation was 17.7 (p 0.05). The au- “on-demand” repeat dilation sessions, if needed. They thors concluded that laparoscopic myotomy and partial fundoplication was superior to pneumatic dilation in found initial symptom remission to be 91.3% after a me- newly diagnosed patients with achalasia. dian of 2.6 dilations. Recurrent symptoms developed in 35% of patients. At 5 and 10 years, the calculated proba- Surgical treatment bility of being in remission was 67% and 50%, respectively. Esophageal myotomy for achalasia was first described by Of those patients with recurrent symptoms who required Ernest Heller in 1913.45 In this operation, both the anterior repeat dilation treatment, 96.4% were in remission at a and posterior lower esophageal sphincter muscle fibers mean of 3.5 years. The probability of being in remission were disrupted. A modified version of this procedure, re- after repeat dilation was 96.8% and 93.4% at 5 and 10 40 ferred to today as the , consists of a single years, respectively. anterior longitudinal myotomy and has become the stan- Although pneumatic dilation has been found to have a dard operative technique. Once performed through either more lasting effect on dysphagia than Botox injection, out- a thoracotomy or laparotomy, esophageal myotomy is now side of a rigorous dilation protocol, most studies have not performed almost invariably through a laparoscopic demonstrated the longterm outcomes seen after surgical approach. myotomy. Until recently, the only prospective randomized Outcomes of thoracoscopic myotomy have been shown trial comparing pneumatic dilation to surgical myotomy to be inferior to the laparoscopic approach. In a retrospec- 41 was reported by Csendes and colleagues from Chile. They tive evaluation of patients undergoing either thoracoscopic ϭ found that 100% of patients treated with myotomy (n Heller myotomy (n ϭ 30) or laparoscopic Heller myotomy 19) had only mild or no dysphagia at a mean of 3.5 years, as (n ϭ 30), Patti and colleagues46 found laparoscopic myot- compared with only 61% of those treated with balloon omy to be superior with regard to complete dysphagia relief dilation (n ϭ 18).41 Very late followup of this trial has also (70% versus 77%) and development of postoperative re- been published.42 flux (60% versus 10%). Similarly, Stewart and colleagues,47 Twomore recent evaluations are also worth noting. West comparing the outcomes of 24 achalasia patients who had and colleagues43 retrospectively evaluated longterm out- undergone myotomy through a thoracoscopic approach comes of 125 achalasia patients followed prospectively for with 63 patients who had a laparoscopic approach, found Ͼ5 years after pneumatic dilation. In this experience, only that the laparoscopic approach was not only associated 50% of patients had no or occasional (less than once per with decreased operative time, conversion rate, and length week) dysphagia at 5 years, and only 40% at 15 years. of stay, but was also better able to relieve dysphagia and Kostec and colleagues44 recently reported a multicenter prevent heartburn than the thoracoscopic approach. A re- 156 Williams and Peters Achalasia of the Esophagus J Am Coll Surg cent review of studies evaluating thoracoscopic myotomy from 1993 to 2003 (n ϭ 10 studies; 204 patients) and laparoscopic myotomy from 1995 to 2002 (n ϭ 15 studies; 499 patients) by Abir and colleagues48 found symptom relief to occur in 76% versus 94% of patients, respectively. Development of gastroesophageal reflux disease occurred in 35% of patients after thoracoscopic myotomy and 13% of patients after laparoscopic myotomy.48 The inferior symptomatic outcomes seen after a thoracoscopic myot- omy reflect the difficulty in extending the myotomy ade- quately onto the from the chest and the inability to create a fundoplication to counteract development of reflux disease.46-48

Technique: laparoscopic esophageal myotomy and partial fundoplication Figure 4. Mobilized esophagus and creation of an esophageal my- otomy by separation of the muscle edges down to esophageal The patient is placed on the table in the modified lithot- mucosa and then proximally onto the esophagus and distally onto omy position with the lower extremities abducted; posi- the stomach. tioning identical to that of a laparoscopic fundoplication. is established and four additional An anterior partial fundoplication of the Dor type is the ports are placed under video laparoscopic control. The dis- most commonly performed antireflux barrier created after section begins by freeing the upper third of the gastric myotomy for achalasia. After fundic mobilization the an- fundus in preparation for later Dor anterior hemifundop- terior fundus is laid across the myotomy site and the left lication. The short gastric vessels are sequentially dissected fundic edge is sewn to the left cut edge of the esophageal and divided with the aid of ultrasonic shears. In contrast to myotomy with three or four interrupted sutures of 2-0 silk. a Nissen fundoplication for gastroesophageal reflux disease, The highest stitch is taken through the left crural pillar as the posterior attachments and pancreaticogastric branches an anchor to prevent torsion of the fundus. The fundus is should not be divided, in an effort to preserve as much of then sewn to the right edge of the cut esophageal muscle the normal posterior gastroesophageal anatomy as possible. similarly; again using three or four interrupted sutures of If a Toupetposterior hemifundoplication is planned, a pos- 2-0 silk and taking the highest stitch through the right terior dissection is necessary. This would be the preferred crural pillar to prevent torsion.49 approach in the small (4% to 5%) subset of patients who Tocreate a posterior partial fundoplication (Toupet),the present with a concomitant hiatal . anterior fundus is brought to either side of the myotomy, The gastroesophageal junction is then exposed by dis- and two columns of sutures are placed on either side, leav- secting the gastroesophageal fat pad and retracting it later- ing the myotomy site bare and open.49 ally. The gastroesophageal junction is cleared for 6 to 8 cm in preparation for the myotomy. A vessel loop can be placed around the gastroesophageal junction, including the ante- DATA SUPPORTING TECHNICAL COMPONENTS rior vagus nerve, and brought out through the subxiphoid Extent of myotomy trocar if necessary. Once the esophagus is mobilized and Recent data show that both the proximal and distal extent gastroesophageal junction exposed, the myotomy is per- of esophageal myotomy are important. Chen and col- formed with a combination of scissors and hook-type elec- leagues49 have reported that epiphrenic pseudodiverticu- trocautery (Fig. 4). The extent of the myotomy should be lum developed in as many as 67% of patients followed 7 to limited proximally by the anterior crural confluence and to 16 years post myotomy and fundoplication. This is likely that which can be covered by a fundoplication. It should then caused by an absence of coverage by the fundoplication be carried down across the gastroesophageal junction, to en- over the proximal extent of the myotomy. This increased sure that the clasp fibers are divided, and onto the anterior wall recognition of the potential for diverticulum formation has of the fundus of the stomach for 2 to 3 cm. The edges of the led many to limit the proximal extent of the myotomy to myotomy are carefully separated from the underlying mucosa that which can be covered by a fundoplication. for 40% to 50% of the esophageal circumference. The proce- Relief of dysphagia might be better when lengthening dure is completed by fashioning an anterior (Dor) or posterior the distal extent of myotomy. Oelschlager and colleagues51 (Toupet) partial fundoplication. reported better symptomatic improvement and a lower in- Vol. 208, No. 1, January 2009 Williams and Peters Achalasia of the Esophagus 157

Table 2. Outcomes after Laparoscopic Heller Myotomy Followup, mo Relief of Length of stay, Perforations Reflux First author Year n (range) dysphagia (%) d (range) (%) (%) Portale55 2005 248 43 (1Ϫ131) 88 5 (3Ϫ11) 4 7* Bonatti56 2005 75 64 (10Ϫ131) 84 2 (1Ϫ6) 4 11 Khajanchee57 2005 121 9 (6Ϫ48) 91 1.7 (NA) 6.6 13* Arain54 2004 78 24 (6Ϫ100) 77 NA 0 17 Perrone58 2004 100 26 (6Ϫ72) 96 1.2 (1Ϫ4) 3 NA Oelschlager50 2003 110 26 (1Ϫ85) 90 NA NA 23 Donahue59 2002 81 45 (1Ϫ70) 84 1 (NA) 14 4 Sharp60 2002 100 11 (NA) 93 1.5 (NA) 8 4 Zaninotto61 2002 113 24 (1Ϫ83) 91 NA NA 6 Patti62 1999 133 23 (NA) 89 2 5 17 *Based on postoperative 24-hour pH monitoring. NA, not available. cidence of recurrent dysphagia by increasing the distal ex- plication to Heller myotomy did not decrease esophageal tent of myotomy onto the proximal stomach from 1.5 cm emptying when assessed by barium esophagography. to 3 cm. They compared outcomes of 52 patients treated In the presence of an aperistaltic, often dilated and tor- with a standard myotomy of 1.5 cm onto the proximal tuous esophagus, most agree that a complete fundoplica- stomach with outcomes of 58 patients treated with an ex- tion should be avoided.54 On the other hand, the precise tended myotomy of 3 cm. Postoperative LES pressures degree (ie, 180 degrees, 270 degrees) and location (anterior, were substantially lower (9.5 mmHg with extended versus posterior) of a partial fundoplication is unclear. Current 15.8 mmHg with standard myotomy) and postoperative data suggests a minimal difference between a posterior dysphagia improved after longer myotomy. Importantly, 270-degree (Toupet) fundoplication and an anterior 90- to postoperative 24-hour pH data showed that extension of 180-degree (Dor) fundoplication. For example, Arain and the distal aspect of the myotomy did not result in a higher colleagues54 found no difference in relief of symptoms, in- prevalence of gastroesophageal reflux. cluding dysphagia, heartburn, or chest pain, or the need for proton-pump inhibitors when comparing myotomy with Dor to myotomy with Toupet. Because of the preservation Addition of fundoplication of natural posterior attachments and its easier technical Although myotomy effectively lowers esophageal outflow construction, most centers have migrated toward routine resistance and improves esophageal emptying, it also in- use of a Dor fundoplication. creases the propensity for development of gastroesophageal reflux. The importance of the addition of a fundoplication to the myotomy has, until recently, been debated. SURGICAL OUTCOMES A recent prospective randomized study has put this issue Outcomes of laparoscopic Heller myotomy have now been to rest. Richards and colleagues52 reported on 43 achalasia studied for well more than a decade. These data show that patients randomized to laparoscopic Heller myotomy with surgical myotomy is more effective than nonsurgical treat- and without Dor fundoplication. Gastroesophageal reflux, ments at providing longterm relief of dysphagia, regurgita- defined by 24-hour distal esophageal acid exposure time tion, and chest pain, while promoting weight gain and Ͼ4.2%, was present in 47.5% of patients undergoing patient satisfaction. Many surgeons and gastroenterologists Heller myotomy alone compared with 9.1% of patients alike believe that surgical myotomy should be recom- undergoing Heller myotomy with partial fundoplication. mended as primary therapy for virtually all patients with Importantly, there was no substantial difference in post- achalasia.51,55-63 operative LES pressures or dysphagia scores between the Medium-term outcomes of laparoscopic myotomy two groups. Similarly, a retrospective evaluation of 146 have been reported from centers around the world patients who underwent laparoscopic Heller myotomy (Table 2).51,55-63 Assessed 2 to 5 years after operation, with (n ϭ 88) or without (n ϭ 61) Dor fundoplication by Ͼ90% of patients have either complete relief of, or only Rice and colleagues,53 found that pH proved gastroesoph- mild persistent, dysphagia. Investigators from Padua, ageal reflux occurred considerably less often after addition Italy, have provided some of the longest-term data. Por- of a partial fundoplication.53 The addition of Dor fundo- tale and colleagues,56 reported 113 patients who under- 158 Williams and Peters Achalasia of the Esophagus J Am Coll Surg went laparoscopic Heller myotomy from 1992 to 1999. More than 90% (91.2%) were symptom-free at a median of 2 years followup, with a Kaplan-Meier analysis showing a 90% probability of remaining asymptomatic at 5 years. Most published results report similar improvement. De- gree of improvement might not be the same with all symp- toms. Arain and colleagues54 found that the most marked improvement occurred for the symptom of regurgitation (74% complete relief). Moderate relief was seen for dys- phagia (33% complete relief) and the least relief was ob- served for chest pain (18% complete relief). Difficulty in relieving chest pain has also been reported after pneumatic dilation.64 Complications average 10% to 15%, and commonly include pneumothorax, wound , and esophageal 47,55-63 leak. Mortality is uncommon, zero in most large pub- Figure 5. Proportion of patients with normal and abnormal esoph- lished series. Inadvertent violation of the esophageal mu- ageal acid exposure after myotomy and partial fundoplication for cosa occurs in 0 to 14% of procedures and, when recog- achalasia. Group 1: Ͻ10 years, group 2: 10 to 20 years, group 3: nized and repaired, is rarely of clinical consequence. Ͼ30 years followup. Gray bar, normal acid reflux test; black bar, abnormal acid reflux test. Reprinted from: Csendes A, Braghetto I, Unrecognized mucosal perforation will present as acute Burdiles P, et al. Very late results of esophagomyotomy for patients abdominal or chest pain in the early postoperative period with achalasia; clinical endoscopic, histologic, manometric and acid and has been treated both operatively and nonoperatively. reflux studies in 67 patients for a mean follow-up of 190 months. Conversion from a laparoscopic operation to open laparot- Ann Surg 2006;243:196Ϫ203, with permission. omy is infrequent in experienced laparoscopic centers and is caused by esophageal perforation, uncontrolled hemor- Ͼ30 years postmyotomy. Similarly, there was a slowly pro- rhage, or adhesions. gressive increase in patients found to have pathologic Postoperative assessment through contrast esophagogra- esophageal acid exposure 15%, 28%, and 53% respectively phy, manometry, and pH monitoring has shown that (Fig. 5). Barrett’s esophagus developed in nine patients and esophageal outflow obstruction improves and esophageal esophageal squamous cell carcinoma developed in three. diameter decreases, as does resting and residual LES pres- 62 sure. Zaninotto and colleagues, reported pH data on 84 Outcomes predictors of 113 patients who underwent postoperative 24-hour pH Several factors have been proposed as predictors of out- monitoring. Only 5 of 84 (6%) had tracings consistent comes after treatment for achalasia. Degree of improve- with gastroesophageal reflux, three of these reported mild ment in the resting LES pressure has been reported by heartburn and one had erosive at endoscopy. several authors to substantially affect longterm success of Longterm followup data from the era of open myotomy pneumatic dilation. Patients in whom the LES pressure was suggest that gastroesophageal reflux is a common cause of reduced to Յ10 mmHg had long-lasting (5 years or more) recurrent symptoms, with a substantial minority develop- relief of dysphagia, and recurrent dysphagia developed ing progressive regurgitation, heartburn/chest pain, erosive within the first 12 to 24 months in those with persistent esophagitis, and Barrett’s esophagus. Whether this will also LES pressures Ͼ20 mmHg (Fig. 6).65 This principle is be true of the laparoscopic era remains to be determined. likely as true for surgical myotomy as it is for pneumatic Providing the longest followup of surgical myotomy ever dilation, although lowering resting LES pressure to near 10 reported, Csendes and colleagues42 published the clinical, mmHg is much more reproducible with myotomy. Young endoscopic, histologic, manometric, and acid reflux studies patients (younger than 40 years) have also been shown to of 67 patients enrolled in a prospective randomized study respond less well to pneumatic dilation and are good can- carried out in the 1970s. Patients were divided into three didates for primary myotomy. In a longterm prospective groups based on the length of followup; 6 to 10 years, 10 to study comparing outcomes of patients who required my- 20 years, and 20 to 30 years. Most patients (73%) had otomy after failed pneumatic dilation with patients who long-lasting symptomatic response, although substantial responded well to dilation therapy, Gockel and colleagues66 recurrent symptoms were found in 7% of patients Ͻ10 found that the younger the patient age at diagnosis the years, 23% of those 10 to 20 years, and 35% of patients greater the probability of needing surgical myotomy for Vol. 208, No. 1, January 2009 Williams and Peters Achalasia of the Esophagus 159

Figure 6. Kaplan-Meier curve demonstrating time to symptom re- currence after lower esophageal sphincter pneumatic dilation to pressures of Ͻ10 mmHg, 10 to Ͻ20 mmHg, and Ն20 mmHg. Figure 7. Relative probability of the need for operation based on the Reprinted from: Eckardt VF, Gockel I, Bernhard G. Pneumatic dila- patients age at first diagnosis. Reprinted from: Gockel I, Junginger T, tion for achalasia: late results of a prospective follow up investiga- Bernhard G, Eckardt VF. Heller myotomy for failed pneumatic dilation Ϫ tion. Gut 2004;53:629Ϫ633, with permission . in achalasia: how effective is it? Ann Surg 2004;239:371 377, with permission. symptomatic relief. Using odds ratios to determine risk for of preoperative esophageal dilation or tortuosity, or eventual myotomy, the authors found that a patient diag- both, and the presence or absence of earlier nonopera- nosed with achalasia at age 15 has a 70% probability of tive interventions. needing myotomy, a patient diagnosed at age 40 has a 35% Evaluating outcomes of 78 consecutive achalasia pa- probability and a patient at diagnosed at age 70 has an 8% tients treated with laparoscopic myotomy, Arain and col- probability (Fig. 7). leagues54 found that a high preoperative resting LES pres- Several factors have also been suggested to affect out- sure was an independent predictor of relief of dysphagia. comes of laparoscopic myotomy.These include the mag- This was confirmed in a recent series of 200 consecutively nitude of preoperative LES resting pressure, the degree treated achalasia patients by investigators at Vanderbilt University.67 They found that patients with a preoperative LES resting pressure of Ͼ35 mmHg were 21.3 times more likely to have relief of their dysphagia than those with pre- operative LES pressures Ͻ35 mmHg. These authors also reported that the greater the decrease in LES pressure after operation, the greater the improvement in postoperative dysphagia (Fig. 8). The benefit of surgical myotomy in patients with a di- lated and tortuous esophagus is unclear. In this setting, in which the esophagus is not only massively dilated but sigmoid-shaped, bolus flow is impaired by the shape of the esophagus in addition to LES spasm. Even in these circum- stances, patients can perceive benefits. Patti and col- leagues,68 evaluating 66 patients with varying degrees of dilation, found that all 7 patients with esophageal diame- ters of Ͼ6 cm and tortuosity had satisfactory outcomes. In contrast, a case-controlled study by Pechlivanides and col- Figure 8. Correlation between the change in lower esophageal leagues69 found that esophageal diameter decreased in all sphincter pressure and change in dysphagia score after Heller patients with esophageal dilation, but only patients with a myotomy. LES, lower esophageal sphincter. Reprinted from: Tor- Ͻ quati A, Richards WO, Holzman MD, Sharp KW. Laparoscopic myot- postoperative diameter of 4 cm experienced excellent re- 69 omy for achalasia: predictors of successful outcome after 200 sults. Given this data and the low morbidity and mortal- cases. Ann Surg 2006;243:587Ϫ593, with permission. ity associated with laparoscopic Heller myotomy as com- 160 Williams and Peters Achalasia of the Esophagus J Am Coll Surg pared with , myotomy is often chosen as the or remyotomy for suspected incomplete or scarred myot- first line of treatment regardless of the extent of dilation. omy, and esophagectomy for those with end-stage dilation Endoscopic interventions performed in achalasia pa- and tortuosity, stricture, or cancer. Pneumatic dilation, tients before surgical intervention likely influence the suc- once believed to be contraindicated after myotomy, can be cess of surgical myotomy. Smith and colleagues,33 recently an attractive option for early persistent dysphagia. In a reported that previously given treatment can effect symp- retrospective analysis of 113 patients treated with myot- ϭ tomatic outcomes. Patients with (n 154) or without omy for achalasia, Zaninotto and colleagues62 found that ϭ (n 55) a history of earlier balloon dilation or Botox 78% of 10 patients with recurrent dysphagia could be ef- injection were compared. Defined as persistent or recurrent fectively treated with pneumatic dilation. They concluded symptoms or the need for additional treatment, the failure that pneumatic dilation should be considered as the first- rate of those with earlier interventions was found to be line treatment for patients with persistent dysphagia and almost twice that of those who had no earlier intervention that reoperation should be reserved for those who do not (19.5% versus 10.1%). In addition, patients with previous respond. endoscopic therapies were found to have more difficult Both medical and surgical therapies exist as treatment dissection planes, increased mediastinal scarring, which re- options for patients with achalasia. Administration of phar- sulted in a higher incidence of intraoperative mucosal per- forations, and longer postoperative recovery than those macologic agents have had very little clinical effect. Botox without earlier treatment. These findings support use of injection has shown symptomatic relief in some, but is surgical myotomy as the initial treatment method for acha- often transient, requires multiple treatment sessions, and lasia and put forth that endoscopic interventions should be can make later surgical treatment more difficult. Although reserved for the rare patient who is not a surgical candidate. pneumatic dilation has been found to have a more lasting effect on dysphagia than Botox injection, it has not dem- Persistent or recurrent symptoms onstrated the longer-lasting outcomes seen with surgical Longterm outcomes data suggest that a properly performed myotomy. Laparoscopic Heller myotomy has become the laparoscopic myotomy and partial fundoplication will be initial primary treatment and standard surgical approach the only therapeutic intervention required in up to 80% of for patients with achalasia. patients with achalasia.70 Mild to moderate symptoms of Several studies have shown surgical myotomy to provide dysphagia, regurgitation, heartburn, and chest pain recur superior longterm symptom relief as compared with non- with time in as many as 40% to 50% of patients, but few of surgical interventions. An extended distal myotomy, along these require additional intervention beyond lifestyle and with a partial fundoplication, has been found to provide behavioral changes or proton-pump inhibitor therapy. greater dysphagia relief with minimal development of gas- Mechanisms of failure include inadequate myotomy, scar- troesophageal reflux. A high preoperative LES pressure ring or anatomic distortion of the gastroesophageal junc- portends better symptomatic outcomes after operation, as tion, complications of gastroesophageal reflux disease, and does the absence of earlier nonoperative interventions. Per- progressive esophageal dilation or distortion, usually sec- sistent or recurrent symptoms after surgical myotomy that ondary to persistent outflow resistance. Early failures are do not respond to lifestyle changes can be treated effectively usually caused by failure to extend the myotomy far enough with pneumatic dilation. onto the stomach or anatomic distortion, or both. 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