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Case of early Barrett cancer following peroral endoscopic myotomy
  1. Yervant Ichkhanian1,
  2. Petros Benias2,
  3. Mouen A Khashab1
  1. 1 Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, Maryland, USA
  2. 2 Division of Gastroenterology, Department of Medicine, Hofstra Northwell School of Medicine, Northwell Health System, North Shore University Hospital, Manhasset, New York, USA
  1. Correspondence to Dr Mouen A Khashab, Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, MD 21287, USA; mkhasha1{at}jhmi.edu

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Peroral endoscopic myotomy (POEM) offers an effective and a minimally invasive approach for the management of patients with achalasia and is now considered the standard of care at many centres around the world. Despite its excellent outcomes, the high incidence of postoperative GORD remains its major limitation. Unlike laparoscopic Heller myotomy (LHM), no concomitant fundoplication is performed during POEM, which can increase the incidence of GORD and its long-term consequences. Recently, we diagnosed a case of de novo Barrett’s oesophagus (BE) with oesophageal adenocarcinoma in a patient, 4 years after POEM was performed for achalasia, highlighting the possible long-term consequences of postprocedural GORD.

In more details

Since it was first clinically described,1 POEM has gained worldwide acceptance as an endoscopic technique for the management of achalasia. Despite its well-established efficacy and safety, the development of GORD post-POEM remains a major concern.2 Of particular concern is that up to two-thirds of patients have asymptomatic and unrecognised GORD.3 The effectiveness of our current management and monitoring strategies for GORD following POEM is not well established. In addition, long-term data pertinent to chronic oesophageal acid exposure after POEM are lacking.

The following case is of a 69-year-old man who initially presented at the age of 64 with a 15-year history of dysphagia, regurgitation, microaspiration and intermittent chest pain, and high-resolution oesophageal manometry (HREM) was consistent with type III achalasia. Impedance-pH study was negative for underlying gastro-oesophageal reflux (GER), and the patient had no additional pertinent medical, surgical or family history.

POEM was performed with a 17 cm oesophageal myotomy and 2 cm gastric myotomy with no adverse events. Postprocedure, the distensibility index increased from a baseline value of 1.7 mm2/mm Hg to 6.3 mm2/mm Hg using the endoluminal functional lumen imaging probe (EndoFLIP), and oesophagram revealed proper lower oesophagus emptying with no signs of contrast extravasation. On 2-week postprocedure follow-up, the patient had improvement of his Eckardt score from 7 to 0, and he was advised to continue to take proton pump inhibitor (PPI) (ie, pantoprazole) 40 mg twice daily.

At 2 months post-POEM, the patient had an episode of dysphagia necessitating an upper endoscopy which revealed mild grade A oesophagitis despite his adherence to full-dose PPI therapy. Follow-up HREM and oesophageal impedance-pH study (off PPI) were performed 3 months post-POEM. HREM revealed residual oesophageal compression and spasm with a mean integrated relaxation pressure (IRP) of 7.9 mm Hg, while the pH study showed an overall acid exposure of 12% indicating ongoing acid reflux. As a result, the patient was strongly advised to continue his full-dose PPI and follow an antireflux lifestyle modification.

The patient did well until 4 years post-POEM, when he had a relapse of his symptoms and started complaining of increasing episodes of cough, dysphagia and regurgitation, in addition to more noticeable heart burn despite his adherence to an antireflux regimen (now lansoprazole 30 mg twice daily and ranitidine 300 mg at night-time). Subsequently, an oesophagram was performed which revealed mild oesophageal reflux with mild distal oesophageal tapering with no evidence of achalasia. A repeat pH-impedance study revealed abnormal oesophageal acid exposure in the recumbent position and an overall abnormal total number of reflux episodes (DeMeester score 23.1) with 40% symptom correlation. HREM showed an aperistaltic oesophagus with a mean IRP of 5.7 mm Hg. Outside upper endoscopy revealed salmon-coloured mucosa suggestive of short-segment BE, Prague classification C1M2, with a nodule. Pathology revealed BE and intramucosal carcinoma with a background of high-grade dysplasia. This was confirmed by a second expert pathologist at our tertiary centre.

Repeat endoscopy at our centre revealed short-segment BE with a 1 cm nodule at the gastro-oesophageal junection (GEJ) and Los Angeles grade A oesophagitis. The nodule was resected using band-endoscopic mucosal resection technique, and histopathological evaluation was consistent with a small (<1 mm) focus of intramucosal adenocarcinoma (pT1a) within BE with superficial invasion up to the lamina propria layer. Resected lesion had clear deep and lateral margins with absence of lymphovascular invasion and poorly differentiated components (figure 1).

Figure 1

Upper endoscopic evaluation and resection of oesophageal lesion. (A) In the distal oesophagus, salmon-coloured mucosa suggestive of short-segment Barrett’s oesophagus (Prague classification C1M2) can be appreciated. Los Angeles grade A oesophagitis can be noted as well. (B) The lesion at the gastro-oesophageal junction arising within the areas of Barrett’s oesophagus can be seen. (C) Using band-endoscopic mucosal resection technique, the lesion was resected. (D) Postresection endoscopic view showing no residual lesion. (E, F) Pathology images showing adenocarcinoma (pT1a) in Barrett’s mucosa in a background of oxyntic mucosa with polypoid foveolar hyperplasia. Lateral and deep margins were free of dysplastic tissue.

Comment

POEM can be considered the endoscopic equivalent of LHM; however, it has not historically been combined with an antireflux procedure in the same session. This has been defended by the fact that unlike LHM, POEM preserves the angle of His and the ligamentous attachments of the diaphragm to the oesophagus. These are important barriers to GER, and as such it has been believed that reflux disease is not a major occurrence after POEM. On the other hand, the end result of both procedures is the dissection of the lower oesophageal sphincter, thereby disrupting the main antireflux barrier. The evolution of LHM has been such that it is rarely performed without a concurrent antireflux procedure.

A recent meta-analysis including 2507 cases found an overall reduction of GER from 31.5% to 8.8% with the addition of a partial fundoplication.4

However, the benefits of hemifundoplication addition seem to temporarily reduce the inevitable reflux that results following the disruption of the lower oesophageal sphincter with LHM.5 In an effort to look for the long-term antireflux efficacy of partial fundoplication, one study noted that 12% of 182 patients who had surgical myotomy with partial fundoplication continued to have occasional or continuous heart burn symptoms at a median of 18.3 years postsurgery. Oesophagitis and BE were found in 14.5% and 0.8% of patients, respectively.6 Another study found that 6% of 400 patients had evidence of GER on pH monitoring at a median time of 30 months post-Heller myotomy.7 These data raise the concern of the long-term and possibly the catastrophic outcomes of postprocedural GORD. For instance, squamous cancer was reported in 3 out of the total 67 patients in a study with long-term follow-up after open Heller myotomy with Dor hemifundoplication.8 Notably, in a large database of 2896 patients who were diagnosed with achalasia and managed with surgical myotomy and pneumatic dilation, both squamous cell and to a lesser extent adenocarcinoma were reported during long-term follow-up.9 In a study that included 331 patients with achalasia treated with pneumatic dilation and followed up for a mean of 8.9 years, BE developed in 28 (8.4%) patients, 2 of whom subsequently developed oesophageal adenocarcinoma.10

Similarly, patients with achalasia undergoing successful POEM are expected to be at least at a similar risk of developing BE during long-term follow-up considering the absence of concomitant antireflux procedure. Although long-term data on POEM are scarce, the short-term development of GER following POEM is well described.11–15 While rates of GORD following POEM may vary in the literature, objective 24-hour pH testing has consistently shown that abnormal oesophageal acid exposure occurs in over 40% of patients. In addition, it is also quite common for post-POEM patients to develop asymptomatic GER. In a multicentre case–control study, it was reported that 60% of patients who developed GER post-POEM were asymptomatic.3 In the current case, the patient was adherent to his full-dose PPI therapy and denied symptoms of GER in the first 3 years post-POEM. However, clinical outcomes at 4 years undoubtedly indicate that the patient’s GER was suboptimally treated.

A recent systematic review by Repici et al 16 demonstrated that the incidence of reflux was twofold to threefold higher in patients following POEM as compared with those who had undergone LHM with fundoplication. This was reported across all three parameters, symptoms (19.0% POEM vs 8.8% LHM), abnormal pH study (39% POEM vs 17% LHM) and oesophagitis (28% POEM vs 7.6% LHM).16 Most recently, the interim analysis of a randomised clinical trial17 comparing POEM with pneumatic dilatation revealed superior efficacy for POEM; however, off-PPI endoscopy surveillance revealed significantly higher incidence of oesophagitis in the POEM group (40% grade A/B and 8.3% grade C/D, vs 13.1% grade A/B and 0% grade C/D, p=0.02).

Algorithmic approach to studying and managing reflux post-POEM

According to the most recent American Gastroenterological Association recommendation,18 ‘post-POEM patients should be considered high risk to develop reflux esophagitis and advised of the management considerations (potential indefinite proton pump inhibitor therapy and/or surveillance endoscopy) of this before undergoing the procedure’. Physicians should clearly state that the risk of developing reflux post-POEM is significant and advise adherence to postprocedure management which includes (1) objective testing for oesophageal acid exposure, (2) long-term and possible lifelong PPI use, and (3) surveillance for long-term consequences of GER, preferably via yearly upper endoscopy. It is important to acknowledge that the lack of symptoms or the absence of endoscopic evidence of GER on initial endoscopy does not necessarily rule out GER. For instance, Werner et al 19 reported that 31% of post-POEM patients with clinically successful outcome and absence of reflux oesophagitis on their first surveillance endoscopy eventually developed oesophagitis at subsequent surveillance endoscopy done at a mean follow-up of 29 months, with two developing short-segment BE.

Adjunct antireflux procedure with POEM

Another question that needs to be addressed is whether committing patients to long-term PPI use is sufficient for preventing long-term consequences of GORD. PPIs alone are suggested to have limited protective ability against the synergistic effect of both acid and bile reflux on oesophageal mucosal injury.20 In the current case, the patient was consistently on some form of medical treatment for reflux after his POEM. Unfortunately, the severity of GORD was enough to cause an early oesophageal adenocarcinoma in the setting of BE. Taking into consideration the relatively young age group of many of POEM patients and the frequent need for lifelong protection from abnormal acid exposure, an antireflux procedure might be a more ideal long-term option as compared with long-term medical therapy. Transoral incisionless fundoplication (TIF) has been proposed as a potential endoscopic solution for GER post-POEM.21 We have performed the first case of same-session TIF following POEM procedure (figure 2). The two procedures were carried out concomitantly with technical success and no adverse events. The role of TIF in the prevention of post-POEM GER deserves further studying.

Figure 2

POEM and TIF procedure during the same session for a 68-year-old man with achalasia. (A) Endoscopic view of the submucosal tunnel that was created during POEM. (B) Following POEM, the incision was securely closed with endoscopic suturing using two interrupted sutures before proceeding with the TIF procedure. (C, D, E) The patient was positioned in the left lateral position and the EsophyX Z device was inserted. Partial (270°) gastric fundoplication was carried out at approximately 1 cm above the angle of His. (F) Endoscopic retroflex view following the completion of TIF. POEM, peroral endoscopic myotomy; TIF, transoral incisionless fundoplication.

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Footnotes

  • Correction notice This article has been corrected since it published Online First. The last author's name has been corrected.

  • Contributors MK and YI drafted the article. MK and PB critically revised the manuscript for important intellectual content.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests MK is a consultant for Boston Scientific, Medtronic and Olympus.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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