The injection of botulinum toxin into the LES has been a popular form of palliation since it was first described by Pasricha et al. [11], in 1993. The typical treatment regime is the injection of 100 units of reconstituted Botox, divided into four aliquots, into the LES in four quadrants. This can also be done under endoscopic ultrasound visualization, even though there is no convincing evidence that it improves outcome. While Botox is safe, relatively effective (80% early dysphagia relief) and minimally invasive, it has two major drawbacks that prevent it from being a frontline treatment [12]. The first is its transient effectiveness. Despite good early results, the effect substantially fades over time, with 60% of patients having recurrent dysphagia at 1 year and 80% at 2 years. The second is that intramuscular Botox injections cause submucosal fibrosis, which interferes with subsequent definitive treatments [13]. For these reasons, Botox is generally recommended only for patients who are poor medical candidates for definitive treatment or as a transient palliation for very acute cases (e.g., total outlet obstruction in patients in whom timely, definitive treatment is not possible) [14].

The popularity of pneumatic dilation (PD) has waxed and waned for several decades. The technique involves placement of a fixed-diameter, high-pressure dilating balloon across the LES, usually under fluoroscopic visualization. Dilation is performed until the balloon waist is seen to disappear. The balloons are typically 30 or 35 mm in diameter, with most current protocols calling for dilation with the 30-mm balloon followed by the 35-mm balloon if adequate results are not obtained [15]. Early results are good, with 70% of patients experiencing a substantial relief of dysphagia at 6 months after a mean of two dilation episodes [16]. However, late-term follow-up has documented decreasing success over time, with only 36% of patients still having dysphagia relief after 20 years [17]. Several studies have shown better results with PD in patients over 40 years of age [18] and worse outcomes in patients with Chicago type III achalasia (60% vs. 93% Chicago I/II) [19]. The risk of esophageal perforation is 3% to 6%, which is the major reason why PD remains controversial in terms of its acceptance [20], although most of the perforations occurring with PD can be treated conservatively [21]. Impedance planimetry using a proprietary 30-mm balloon allows achalasia dilation without fluoroscopy and under very controlled conditions. It may rejuvenate interest in PD (Fig. 4).

A minimally invasive Heller myotomy (HM) involving a thoracoscopic approach was first described by Pellegrini et al. [22]. Yet, while the thoracoscopic approach replicated the classic open surgical method it was quickly abandoned due to poor results [23]. Subsequently, excellent results and great patient benefit were obtained using a laparoscopic approach, which quickly became the gold standard surgical treatment [24,25]. A landmark study by Richards et al. [26] from Vanderbilt University (Nashville, TN, USA), confirmed the need to add a partial fundoplication to the myotomy to minimize the incidence of iatrogenic GERD.

Laparoscopic HM has become a fairly well-standardized procedure: a five-laparoscopic port approach is used, with mobilization of at least the anterior 180° of the gastroesophageal junction and distal esophagus (360° if a Toupet is planned) followed by a full-thickness myotomy that is extended to the distal esophagus at least until the hiatus of the diaphragm. We tend to avoid extension of the myotomy into the free mediastinum due to the risk of late-term saccular dilation of the myotomy site. The traditional 2-cm extension of the myotomy onto the anterior stomach wall has been challenged by a prospective study by Oelschlager et al. [27], which showed better outcomes with a 3-cm extension.

The type of fundoplication that is added following the myotomy remains controversial. The Dor anterior 180° wrap and the Toupet 270° posterior wrap are the most commonly used, but there are rare anecdotal reports advocating a 360° Nissen fundoplication. Among the arguments for the Dor procedure are that it requires less hiatal dissection and covers the exposed mucosa of the myotomy site, which may offer protection in case of perforation. Advocates of the Toupet procedure claim that its 270° wrap prevents reflux more effectively, and that fixation to the edges of the myotomy helps to prevent the myotomy site from healing in a closed position. However, there are as yet no studies providing conclusive support for one or the other procedure, and the choice of fundoplication continues to be a matter of the surgeon’s preference [28,29].

POEM is the offspring of the natural orifice transenteric endoscopic surgery (NOTES) procedure adopted in the late 2000s. In seeking a safe exit strategy from the gastrointestinal tract by sub-mucosal tunneling, Pasricha et al. [30] discovered that they could visualize the circular muscle of the LES clearly during tunneling, and proposed that achalasia myotomy would be feasible. They presented a proof of concept in four pigs in 2009 [30]. Inoue et al. [31], a surgical endoscopist, first applied this concept to humans in 2010 and coined the term “POEM.”

POEM utilizes the skills and tools common to advanced surgical endoscopy techniques, such as endoscopic sub-mucosal dissection. The procedure is designed according to the manometry findings, with a short myotomy for Chicago types I and II and a long myotomy for Chicago type III and spastic disorders. A mucosal lift with methylene blue saline is created 3 cm proximal to the planned start of the myotomy and a longitudinal incision extending to the muscularis propria is made. An endoscope fitted with a dissecting cap is introduced into this submucosal plane, after which a tunnel is dissected down to and across the LES and 2 to 3 cm onto the proximal wall of the stomach. Once the tunnel is created, the endoscope is pulled back to the proximal tunnel and the myotomy is started by selectively dividing the circular muscle fibers (Fig. 5). At completion, the mucosal opening is closed using hemostatic clips.

Over the last 10 years, POEM has been rapidly adopted and is now the primary form of treatment at the majority of high-volume achalasia centers. The literature contains an enormous number of studies, both from single centers describing short-term outcomes, including some series with more than 1,000 patients [32], and from multiple centers reporting 1- and 2-year [33,34] and even 5-year [35] outcomes. Together, these reports have confirmed the safety of POEM, as major operative and postoperative complications are rare, as is the need for conversion to a surgical approach. No studies reporting POEM-related mortality have been published to date, although there are anecdotal reports. Summarizing the literature on POEM, successful relief of dysphagia by POEM, as defined by an Eckhardt score < 3, is > 90% after short-term and > 80% after long-term follow-up. The incidence of iatrogenic GERD following POEM in the early days of the procedure varied widely, ranging from no reflux to an incidence of almost 50% [36-38]. As descriptions of GERD symptoms following any type of achalasia treatment are absolutely unreliable [39], the most reliable data are those obtained by pH monitoring. Based on several series reporting objectively determined reflux, the incidence of post-POEM GERD is between 30% and 40% [40]. The incidence of patients whose GERD symptoms cannot be controlled medically and require antireflux surgery is very low.

To date, there have been no randomized prospective studies comparing POEM with other achalasia treatments. This is due, in part, to the rarity of achalasia in the population and to the fact that non-randomized results are highly equivalent to the best endoscopic or surgical treatment, such that powering such a randomization is a daunting proposition. Retrospective comparisons between, in particular, laparoscopic HM and POEM [41] have shown similar rates of complication and a similar safety profile, slightly better relief of dysphagia, and an equal or slightly higher incidence of reflux or reflux symptoms. Again, the differences in these compiled studies between dysphagia relief and GERD incidence are so small, and the disease so rare, that an adequately powered randomized study that truly defines the best treatment cannot reasonably be expected.