of Different Treatment Modalities and Treatment Algorithm for Esophageal Achalasia

Fig. 11.1

Submucosal injection and mucosal incision . (a) Submucosal injection with a solution of saline, indigocarmine, and dilute epinephrine; (b) Mucosectomy with electrocautery. (Reprinted with permission © Springer Nature [95])

../images/473262_1_En_11_Chapter/473262_1_En_11_Fig2_HTML.jpg — Fig. 11.2

Submucosal tunnel creation . (Reprinted with permission © Springer Nature [95])

../images/473262_1_En_11_Chapter/473262_1_En_11_Fig3_HTML.jpg — Fig. 11.3

Myotomy. (Reprinted with permission © Springer Nature [95])

../images/473262_1_En_11_Chapter/473262_1_En_11_Fig4_HTML.png — Fig. 11.4

Closure of the mucosal entry. (a) First clip applied to close the mucosectomy; (b) Mucosectomy clip closure in progress. (Reprinted with permission © Springer Nature [95])

The study showed that POEM significantly improved the dysphagia score in every patient (from mean 10 to 1.3) and reduced the resting LES pressure from a mean of 52.4 mmHg to 19.9 mmHg, without serious complications related to the procedure. This report represented a milestone in the history of the treatment of achalasia. Following Inoue’s study, POEM was introduced in the treatment algorithm of achalasia across the world, and soon many gastroenterologists and surgeons started considering POEM as the primary treatment for achalasia.

Von Renteln et al. [61] conducted a prospective, international, multicenter study involving 70 patients who underwent POEM in 5 centers in Europe and North America, showing improvement at 12 months in 82.4% of patients. In 2015 Inoue [62] studied a cohort of 500 POEM patients and found a significant reduction in Eckardt scores and LES pressure at 2 months, 1 year, and 3 years post procedure. Adverse events rate were 3.2% and there were no mortalities. In 2016, Familiari and colleagues [63] reported the results of POEM in 94 patients, and at a mean follow-up of 11 months, clinical success was achieved in 94.5% of patients. A recent meta-analysis including 36 studies with 2373 patients reported that clinical success (Eckardt score ≤ 3) was achieved in 98% of the patients after POEM [64].

A major concern with POEM has been the high rate of gastroesophageal reflux related to the ablation of LES without any antireflux procedure. In the RCT comparing POEM to PD[50], endoscopy at 1 year follow-up showed that reflux esophagitis was significantly more common in patients treated with POEM (40.0% Los Angeles A or B, 8.3% grade C/D), compared to 13% in those treated with PD (all Los Angeles A or B). Inoue [62] reported on their series of 500 patients that 268 of 414 patients (64.7%) had endoscopic findings of reflux esophagitis. In 2017, Kumbhari et al. [65] performed a multicenter case-control series studying 282 patients and found post-POEM gastroesophageal reflux disease either by endoscopy or pH monitoring in 58% of the patients. Sharata et al. [66] studied with pH monitoring 68 patients after a mean follow-up of 20 months and found an incidence of reflux of 38.2%. Worrell et al. [67] found that 70% of the patients studied with pH monitoring 12 months after POEM had pathologic reflux.

Laparoscopic Heller Myotomy Versus POEM

Potential advantages of POEM over LHM include lack of abdominal incisions, faster recovery, ease of performing a longer myotomy, avoidance of vagal nerve injury, and lack of intra-abdominal adhesions in case surgery is required [68].

Data comparing LHM with POEM are very limited, and to date there have been no randomized controlled trials comparing these treatment modalities. Swanstrom et al. [69] compared the results of LHM (n = 64) and POEM (n = 37), and at a mean follow-up of 6 months, both groups had sustained similar improvements in their Eckardt scores (1.7 vs. 1.2, p = 0.1). Interestingly, post-myotomy resting pressures were higher for POEM than for LHM (16 vs. 7.1 mm Hg, p = 0.006). Bhayani et al. [70] compared LHM and POEM, and at 6 months both groups had similar improvements in their Eckardt score (1.7 vs. 1.2, p = 0.1). Postoperative pH monitoring showed abnormal acid exposure in 39% and 32% of the patients after POEM and LHM, respectively. Chan et al. [71] performed a retrospective cohort study and compared clinical outcomes and quality of life after LHM and POEM; 33 patients underwent POEM and 23 patients underwent LHM. Both procedures achieved similar dysphagia scores at 1, 3, and 6 months and comparable quality-of-life outcomes.

Schlottmann et al. [72] conducted a systematic review and meta-analysis which comprised 53 studies reporting data on LHM (5834 patients) and 21 studies examining POEM (1958 patients). At 24 months, improvement in dysphagia for LHM and POEM was 90.0% and 92.7%, respectively (p = 0.01). Patients undergoing POEM were more likely to develop GERD symptoms (OR 1.69), GERD evidenced by erosive esophagitis (OR 9.31), and GERD evidenced by pH monitoring (OR 4.30).

In patients with type III achalasia (“spastic achalasia”), POEM seems to achieve better outcomes. Kumbhari et al. [65] reported that in patients with type III achalasia, the success rate was 80.8% after LHM and 98.0% after POEM (p = 0.01). Khashab et al. [73] reported a 96.3% successful clinical rate after POEM in 54 patients with type III achalasia refractory to medical therapy. Recently, Zhang et al. [74] studied 32 consecutive patients with type III achalasia treated with POEM, and at a median follow-up of 27 months treatment success was achieved in 90.6% of the patients.

Table 11.1 summarizes outcomes of LHM and POEM in terms of improvement of dysphagia and post-procedural GERD by pH monitoring.

Table 11.1

Outcomes of laparoscopic Heller myotomy (LHM) and per-oral endoscopic myotomy (POEM)

Study (year)	Technique	N	Follow-up (months)	Improvement dysphagia (%)	Reflux pH monitoring (%)
Rossetti (2005) [85]	LHM	195	83.2	91.8	0/15 (0)
Katada (2006 [86]	LHM	30	51	80	3/25 (12)
Zaninotto (2008) [51]	LHM	407	30	90.4	17/260 (6.5)
Rebecchi (2008) [57]	LHM	138	125	91.3	2/138 (1.4)
Sasaki (2010) [87]	LHM	35	94	94.3	0/35 (0)
Parise (2011) [88]	LHM	137	65	94.8	2/15 (13.3)
Di Martino (2011) [89]	LHM	56	24	92.9	4/56 (7.1)
Cuttitta (2011) [90]	LHM	49	75	93.9	2/49 (4.1)
Rosati (2013) [91]	LHM	173	50	99.4	8/47 (17)
Salvador (2016) [92]	LHM	806	49	88.9	40/463 (8.6)
Sharata (2015)[66]	POEM	75	20.1	97.9	26/68 (38.2)
Schneider (2016) [93]	POEM	25	9	91	4/8 (50)
Worrell (2016) [67]	POEM	35	12	90.9	7/10 (70)
Hungness (2016) [94]	POEM	112	28	92	10/22 (45.4)
Familiari (2016) [63]	POEM	100	11	94.5	39/73 (53.4)

LHM laparoscopic Heller myotomy, POEM per-oral endoscopic myotomy

Overall, laparoscopic myotomy and POEM seem to achieve comparable symptomatic improvement rates. However, patients undergoing POEM have a high risk of post-procedural GERD. In patients with type III achalasia, POEM could be considered as the first-line treatment modality.

Failed Laparoscopic Heller Myotomy: What Next?

Approximately 10–20% of patients undergoing LHM will relapse in the mid- or long term and need further treatment. The best treatment for these patients is still under discussion with many options: PD, EBTI, POEM, redo-myotomy, or esophagectomy.

Zaninotto et al. [51] performed 407 LHM with a failure of 10% (39/407 patients). Most of these failures were treated with PD and overcome symptoms in 75% of patients. Schlottmann et al. [75] treated 147 achalasia patients with LHM. At a median follow-up of 22 months, 19 patients had recurrence of symptoms and required additional treatment: 12 patients were successfully treated with PD alone (median 2 PDs/patient), and 4 were successfully treated with combination of PD and EBTI (one session/patient).

PD success rate after LHM seems to be lower than primary PD. However, comparing patients treated with PD after failed myotomy to patients directly undergoing additional surgery showed that the efficacy of PD and redo-surgery were similar [76].

POEM is indeed another option after a failed LHM. A recent study reported 90 patients treated with POEM after LHM failure with clinical success rates of 81% [77].

The 2018 ISDE Achalasia guidelines [6] state that PD rather than repeat myotomy or POEM is the first option for treatment after failed Heller myotomy.

Treatment of End-Stage Achalasia

A severely dilated and sigmoid-shaped esophagus is the final outcome of long-standing untreated achalasia or the result of recurrences and failures of previous treatments (Fig. 11.5). Traditionally, end-stage achalasia was managed by performing an esophagectomy. However, it is well known the high morbidity and mortality associated with this procedure.

../images/473262_1_En_11_Chapter/473262_1_En_11_Fig5_HTML.jpg — Fig. 11.5

End-stage achalasia : barium swallow showing a dilatated and sigmoid-shaped esophagus

PD is considered difficult in patients with end-stage achalasia, and there is limited evidence that PD may be used as first-line therapy. Khan et al. [78] reported 9 patients with megaesophagus (>7 cm diameter) that underwent PD with good symptomatic improvement and no complications at 12 months of follow-up.

A LHM is challenging in these patients because an extensive dissection in the posterior mediastinum is needed to straighten the esophageal axis. In addition, there is usually significant periesophageal inflammation secondary to prior interventions or esophagitis due to long-standing retention of food. Mineo et al. [79] reported their experience in a small cohort of patients and LHM proved to be effective in improving subjective, objective, and quality of life outcome measures in patients with sigmoid esophagus. Similarly, Sweet et al. [80] showed that the outcome of LHM was not influenced by the degree of esophageal dilatation. In 12 patients with an esophageal diameter >6 cm and sigmoid-shaped esophagus, excellent or good results were obtained in 91% of patients, and none required esophagectomy.

POEM also seems to be effective in patients with end-stage achalasia. Hu et al. [81] performed a prospective study in which patients with advanced sigmoid-shaped achalasia were assigned to POEM. In this study, 32 consecutive patients underwent POEM with a treatment success of 96.8% with a mean follow-up of 30 months.

After the failure of all other treatment modalities, esophagectomy should be considered. It is important to promptly identify patients in whom surgical resection will be needed before patients’ nutritional and general conditions become too deteriorated increasing the risk of this major surgery.

The ISDE 2018 Achalasia guidelines [6] recommend standard endoscopic (PD or POEM) or surgical therapies (LHM) in sigmoid-shaped esophagus, leaving esophagectomy as the last option in case of failure of the other treatment modalities.

Algorithm for Achalasia Treatment

Medical therapy and/or endoscopic Botox injection should be considered in patients with advanced age or significant comorbidities who are not candidates for LHM or POEM. Patients who are deemed good surgical candidates should undergo LHM (types I and II) or POEM (type III). Patients who have failed initial treatment should be referred for pneumatic dilatation. If symptoms persist, it is reasonable to consider POEM for those who underwent LHM initially and LHM for those who underwent POEM at first [77, 82–94]. Esophagectomy should be reserved for patients who have failed all these previous interventions (Fig. 11.6).