Pre-procedural Work-Up and Indications

Fig. 17.1

High-resolution manometry parameters. (Courtesy of the Northwestern Esophageal Center)

Once the IRP is determined, the next step in making a manometric diagnosis is to determine the peristaltic activity of the esophagus. The key parameters used to define the peristaltic activity of the esophagus are distal latency (DL) and distal contractile integral (DCI) (Fig. 17.1). The DL identifies premature contractions (spasms) and is defined as the time from the start of upper esophageal sphincter relaxation to the contractile deceleration point (CDP) which is the inflection point along the 30 mmHg isobaric contour at which the propagation velocity slows [10, 27]. Values of less than 4.5 s are considered premature. Contractions are also assessed for their adequacy according to the DCI which is defined as the amplitude∗duration∗length (mmHg∗s∗cm) of a contraction distal to the transition zone and above 20 mmHg [10]. Using the combination of these values, the CC can then be applied to define achalasia, EGJOO, distal esophageal spasm (DES), and jackhammer, the diagnoses amenable to POEM. Beyond diagnosis, HRM can also be used to assess for technical success following POEM with multiple studies showing improvement in IRP and lower esophageal basal pressure following treatment [28–31].

A unique capability of POEM is to perform an extended proximal myotomy, typically dictated by HRM metrics, which is recommended for patients with type III achalasia, type I or II with symptoms of chest pain, abdominal contractions on initial inspection, or spastic motility disorders such as DES or jackhammer [32]. These data are consistent with results that suggest that noncardiac chest pain may be associated with sustained esophageal contractions and studies supporting efficacy in extended surgical myotomy in relieving the pain [33, 34]. Figure 17.2 represents such an example in which a patient had complete symptomatic response (Eckardt score (ES) 6 pretreatment to 0 posttreatment) following an extended 19 cm myotomy for type III achalasia. The pre- and post-POEM EPT plots are shown which demonstrate an improved LES pressure and almost complete loss of the premature hypercontractile segment following therapy.

../images/442926_1_En_17_Chapter/442926_1_En_17_Fig2_HTML.jpg — Fig. 17.2

Type III achalasia treated with extended POEM, (a) Pre-POEM HRM, (b) HRM post 19 cm myotomy. (Courtesy of the Northwestern Esophageal Center)

In addition to standard high-resolution manometry, advanced metrics using impedance manometry may also be useful in identifying those patients that may benefit from POEM. Impedance values decrease with bolus/fluid retention. This allows impedance to act as a surrogate for this cardinal feature of EGJ dysfunction. The impedance bolus height which can be measured during manometry with the addition of a 200 ml saline challenge has been shown to correlate with bolus retention on TBE (Fig. 17.3a) [35]. Furthermore, the esophageal impedance integral ratio, defined as the ratio of bolus that does not clear the esophagus (Z2) to that of bolus that does clear the esophagus (Z1), has also been shown to be aid in the diagnosis of nonobstructive dysphagia and can be used to evaluate treatment outcomes in achalasia (Fig. 17.3b) [36, 37]. Beyond assessing retention, manometry with impedance is also able to measure bolus flow time (BFT) which uses impedance manometry to evaluate EGJ opening and bolus flow using a virtual high-resolution sleeve. This approach relies on a flow-permissive pressure gradient and assesses the nadir impedance as a surrogate of bolus presence within the EGJ [38]. A recent study demonstrated significantly reduced BFTs (median (IQR)) in patients with achalasia compared to healthy controls, 0.45 s (0.0–1.2 s) vs 3.5 s (2.3–3.9 s), respectively. Additionally, BFT was able to identify patients with clinical achalasia and a normal IRP [39].

../images/442926_1_En_17_Chapter/442926_1_En_17_Fig3_HTML.png — Fig. 17.3

Impedance manometry, (a) impedance bolus height corresponds to barium retention on TBE, (b) EII ratio approaches 1 in patient with achalasia (Z2÷Z1), demonstrating significant bolus retention. (Courtesy of the Northwestern Esophageal Center)

Esophagogastroduodenoscopy

As described above, EGD is necessary for the evaluation prior to POEM to ensure a patient does not have high-grade esophagitis or an anatomic etiology for their symptoms. EGD can also be useful in assessing for esophageal dilatation, the presence and location of diverticula, and tortuosity which although is not a contraindication to POEM should be recognized prior to treatment to ensure proper procedural planning. There is also debate in the literature regarding the necessity of EGD to rule out fungal infections prior to POEM. Some centers administer empiric fluconazole or nystatin in all patients for 2–3 days before the procedure, due to the high rate of esophageal stasis and candidiasis, while others treat only overt evidence of fungal overgrowth [40–42]. It is our practice to treat only overt disease prior to POEM.

Timed Barium Esophagram

TBE is a modified version of the barium swallow where patients drink 100–200 ml of low-density barium followed by upright radiographs at defined time intervals, typically 1, 2, and 5 min, post-swallow [43]. This test has classically been used to assess esophageal emptying in patients with achalasia and post-LES targeted therapy to assess for response to treatment. Multiple studies have reported that improvements in TBE correlate with improvement in patient-reported outcomes following treatment for achalasia [44–46]. The test has not been rigorously evaluated as a diagnostic tool but can often aid in defining esophageal anatomy and assessing for esophageal retention which is one of the hallmarks of achalasia aiding in its diagnosis (Fig. 17.4). Furthermore, in the subset of patients with absent peristalsis and borderline IRP values, liquid barium retention may suggest that a patient would benefit from LES targeted therapy such as POEM.

../images/442926_1_En_17_Chapter/442926_1_En_17_Fig4_HTML.jpg — Fig. 17.4

Achalasia subtypes on high-resolution manometry (top panels) and associated timed barium esophagrams (bottom panels). (Courtesy of the Northwestern Esophageal Center)

Endoscopic Ultrasound (EUS) and Computerized Tomography (CT)

These tests are not regularly needed for the assessment of esophageal disease prior to treatment with POEM; however, in specific circumstances, they may help rule out pseudoachalasia due to infiltrative disease or a vascular anomaly [23, 47–53]. A careful history and endoscopic examination may prompt these tests if there is lymphadenopathy, weight loss, or abnormal anatomy on a thorough endoscopic examination including retroflexion to assess the cardia of the stomach.

This is exemplified in Fig. 17.5 which demonstrates a HRM and an esophagram of a patient referred to our esophageal center for pneumatic dilatation. The esophagram has the classic bird-beak pattern associated with achalasia, and the HRM met the criteria for type II achalasia; however, the LES pressure appeared to vary with the patient’s heart rate prompting an EUS. The EUS revealed a large aortic aneurysm compressing the EGJ leading to an outflow obstruction. Fortunately, the patient underwent vascular surgery in lieu of a potentially life-threatening pneumatic dilation.

../images/442926_1_En_17_Chapter/442926_1_En_17_Fig5_HTML.jpg — Fig. 17.5

Pseudoachalasia due to vascular obstruction. (a) HRM, (b) esophagram, (c) EUS. (Courtesy of the Northwestern Esophageal Center)

Functional Luminal Imaging Probe

The FLIP uses high-resolution impedance planimetry to measure esophageal cross-sectional area and simultaneous pressure (distensibility, mm²/mmHg) during volumetric distention. This technology is unique as it allows for the assessment of esophageal motility during sedated upper endoscopy [54]. Patients with treatment-naïve achalasia have consistently demonstrated esophagogastric junction distensibilities (EGJ-DI) less than 2.8 mm²/mmHg, and patients posttreatment for achalasia with an EGJ-DI that remains below 2.8 mm²/mmHg have demonstrated worse outcomes [55–58]. At this point, this technology functions as an adjunct to formal HRM motility diagnoses, but more recent work identifying esophageal body contractions has led to a diagnostic algorithm similar to that used in the CC [54]. In combination with the correct clinical context (HRM with absent peristalsis and normal IRP, barium retention on esophagram, or EGD suggestive of achalasia without evidence of obstructive dysphagia), a FLIP distensibility index of <2.8 mm²/mmHg suggests that these patients may benefit from LES targeted therapy. This has been demonstrated previously in a study of 13 patients with symptoms consistent with achalasia, absent peristalsis but normal IRP on HRM, and distensibility indices consistent with achalasia. These patients were treated with LES targeted therapy (1 Botox, 9 PD, 3 LHM) and subsequently had improvement in EGJ-DI and Eckardt scores [59]. It is our experience that POEM may also be an effective therapy for these patients. Figure 17.6 demonstrates a patient who presented with dysphagia and had absent peristalsis with a normal IRP on HRM. This patient would not meet the criteria for achalasia according to the CC; however, she had an 11 cm barium column on TBE at 5 min and a FLIP with an EGJ-DI of 1.6 mm²/mmHg. Following POEM, she had complete resolution of her symptoms.

../images/442926_1_En_17_Chapter/442926_1_En_17_Fig6_HTML.png — Fig. 17.6

Achalasia in the setting of a normal IRP. (a) HRM, (b) esophagram, (c) FLIP topography. (Courtesy of the Northwestern Esophageal Center)

This technology also offers the ability to assess the LES in real time during POEM, and several studies have demonstrated immediate increases in EGJ-DI at the completion of the procedure [60–63]. Furthermore, a recent study reported that a final intraoperative EGJ-DI in the range of 4.5–8.5 mm²/mmHg was optimal for reducing dysphagia and minimizing gastroesophageal reflux disease at 6 months post-POEM [62].

Indications

POEM was first performed for uncomplicated achalasia, but the technique was quickly adopted for more complex cases including patients with sigmoid anatomy of their esophagus [4]. There is currently no consensus regarding formal indications for POEM, but substantial work has been done to study various treatment applications including achalasia (all three clinical subtypes), non-achalasia motility disorders (DES and jackhammer esophagus), and following failed prior LES targeted therapy for achalasia (Table 17.1).

Table 17.1

Indications for POEM

Indications
Achalasia (all subtypes)
Failed LHM
Failed PD
Failed POEM
Sigmoid anatomy/end stage
Pediatric population
EGJOO
DES
Jackhammer

Achalasia

Achalasia is defined according to the CC as a major motility disorder with an IRP ≥ upper limit of normal (15 mmHg for Sierra design transducers) and 100% failed peristalsis or spasm. Achalasia is subtyped into type I, no contractility; type II, ≥20% pan-esophageal pressurization (with an isobaric contour line of 30 mmHg); or type III, ≥20% spasm with a distal latency of <4.5 s (Fig. 17.4). These subtypes define distinct clinical entities with varying response to different treatments; however, studies suggest that POEM is effective at treating all types of achalasia [64–66]. A prospective multicenter study of POEM demonstrated a 90% clinical success rate [67]. Two meta-analyses of more than 1000 patients each also demonstrated the short-term success of POEM in treating achalasia as measured by reduced ES and LES pressures [68, 69]. Furthermore, POEM appears to be a durable treatment for achalasia with continued response rates >88% in studies assessing patient outcomes ranging from 2 to 5 years [44, 70, 71]. When comparing POEM to PD and LHM, POEM appears to be at least as effective in treating type I and II achalasia and is likely more effective due to the ability to extend the myotomy length in treating type III achalasia [40, 72–74]. FLIP analysis pre- and posttreatment with POEM compared to LHM shows similar increases in the EGJ-DI [60, 61]. Furthermore, POEM had operative times that were similar or up to 30 min faster, less blood loss, similar or less post-op pain, shorter length of hospital stay, and faster return to normal activity compared to LHM [41, 42, 75, 76].

Non-achalasia Motility Disorders

In the hierarchical scheme put forth in the CC, EGJOO, like achalasia, is defined as an elevated IRP; however, there is sufficient peristalsis in isolated EGJOO to exclude classic or spastic achalasia [10] (Fig. 17.7). Intuitively, POEM would seem an ideal treatment for this disease; however, EGJOO currently functions as a catchall diagnosis for a heterogeneous clinical entity making management decisions difficult. Within EGJOO, there is a subset of diseases which have been shown to benefit from POEM including incomplete achalasia or achalasia in evolution, but this represents only a small proportion of patients [52, 77]. A large proportion of patients with EGJOO (20–40%) improve without therapy, and the majority has etiologies which will not respond to LES targeted therapy (e.g., infiltrative disease or cancer, vascular obstruction, hiatal hernia, eosinophilic esophagitis, stricture, abdominal obesity, or prior foregut surgery) [23, 51, 53, 78, 79]. Although some patients with EGJOO may benefit from POEM, the heterogeneity of this diagnosis dictates further evaluation which may include impedance manometry, endoscopic ultrasound, computed tomography, timed barium esophagram, or FLIP. Figure 17.7a demonstrates representative images of HRM (left panel), FLIP (top right panel), and EUS (bottom right panel) for patients with EGJOO who would likely benefit from POEM. The HRM shows a normal distal latency with an elevated IRP to 19.9 mmHg. FLIP analysis of this patient demonstrated an EGJ-DI of 0.73 mm²/mmHg which is less than the cut-off of 2.8 mm²/mmHg and suggests that this patient would benefit from LES targeted therapy. The EUS shown here was also performed on a patient with EGJOO to rule alternative etiologies for the cause of the outlet obstruction. The EUS did not identify an alternative etiology for the outlet obstruction, but it did reveal a thickened muscularis propria to 8 mm suggesting this patient may benefit from POEM.

../images/442926_1_En_17_Chapter/442926_1_En_17_Fig7a_HTML.png — Fig. 17.7

Non-achalasia motility disorders for which POEM is indicated. (a) EGJOO on HRM, FLIP topography with low DI and absent contractility, and muscularis propria thickening on EUS. (b) DES on HRM, FLIP topography with repetitive retrograde contractions, and an impacted barium tablet on esophagram. (c) Jackhammer on HRM with poor bolus clearance and compartmentalization on both impedance manometry 200 ml challenge and an esophagram. (Courtesy of the Northwestern Esophageal Center)

../images/442926_1_En_17_Chapter/442926_1_En_17_Fig7b_HTML.jpg — Fig. 17.7

Non-achalasia motility disorders for which POEM is indicated. (a) EGJOO on HRM, FLIP topography with low DI and absent contractility, and muscularis propria thickening on EUS. (b) DES on HRM, FLIP topography with repetitive retrograde contractions, and an impacted barium tablet on esophagram. (c) Jackhammer on HRM with poor bolus clearance and compartmentalization on both impedance manometry 200 ml challenge and an esophagram. (Courtesy of the Northwestern Esophageal Center)

In 2013, an international survey of 16 expert centers performing POEM demonstrated that 22.5% of patients undergoing POEM at that time were treated for spastic esophageal disorders including DES (≥20% premature contractions, distal latency <4.5 s) and jackhammer esophagus (≥20% of swallows with a distal contractile integral >8000 mmHg/s/cm) [80] (Fig. 17.7b, c). A growing literature and a recent meta-analysis demonstrate the efficacy of this approach with 88% and 72% success in DES and jackhammer, respectively [80–84]. POEM is especially attractive in these diseases as it allows for customization of the myotomy length based on the area of high pressure on HRM, thickening on endoscopic ultrasound, or intraoperative FLIP. Figure 17.7b shows an HRM (left panel), FLIP (top right panel), and esophagram (bottom right panel) of a patient with a manometric diagnosis of DES. The HRM meets the criteria for DES with a normal IRP and a distal latency of less than 4.5 s. The FLIP and esophagram further support the decision to proceed with myotomy given the low EGJ-DI on FLIP and impaction of a 12.5 mm barium tablet on the esophagram. Similarly, Fig. 17.7c demonstrates the HRM (left panel), impedance manometry (top right panel), and an esophagram (bottom right panel) for a patient with jackhammer. The DCI on HRM is significantly elevated to >20,000 mmHg∗s∗cm, and both the impedance manometry and the esophagram demonstrate spastic activity with compartmentalization and liquid retention. These findings suggest that this patient would benefit most from an extended myotomy to the top of the hypercontractile segment.

Special Populations

In the treatment of achalasia, special consideration is given to patients who have failed prior LES targeted therapy (PD, LHM, or POEM) or have abnormal anatomy (esophageal dilatation, sigmoid anatomy, diverticula, and hernias) due to the increased complexity of these individuals. Primary treatment with PD, LHM, and POEM shows near 90% clinical success rates; however, there is a subset of patients who will fail treatment or have recurrent symptoms [1]. In either case, whether it is primary treatment failure due to incomplete myotomy focused at the LES or a more proximal myotomy in type III patients or symptom recurrence due to disease progression or scarring and remodeling at the previous myotomy site, POEM appears to be an effective option for retreatment with clinical success rates ranging from 81% to 100% [4, 70, 85–92].

As a chronic disease, achalasia has the propensity to worsen over time resulting in esophageal dilatation which can often lead to the esophagus taking on a sigmoid shape. POEM has been shown to be >95% effective in both end-stage achalasia and in patients with sigmoid deformity; however, these studies are limited by small numbers of patients and short follow-up periods [4, 93–95]. It is our practice to discuss complex cases at an interdisciplinary meeting with esophagologists and surgeons to determine the best treatment options for these patients with difficult anatomy.

Although the mean age of diagnosis of achalasia is 56, patients can present at any age. There does not appear to be specific age cutoffs for POEM in the treatment of achalasia with case studies demonstrating clinical success in patients ranging from 3 to >90 years old [70, 96–100].

Summary

POEM was first performed less than a decade ago, and its role in the treatment of esophageal motility disorders continues to evolve. There is evidence to support its use in patients with a diagnosis of achalasia (all clinical subtypes), DES and jackhammer esophagus, and a subset of patients with EGJOO. In current practice, these entities are diagnosed with EGD and HRM at a minimum. In difficult cases, additional studies including impedance manometry, TBE, CT, EUS, or FLIP can be used to differentiate patients who may benefit from myotomy and those that will not (Fig. 17.8).