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Dear colleagues and friends,
In this edition of Perspectives, Dr. Mouen Khashab and Dr. Robert Siwiec tackle an exciting and constantly evolving topic, which is the optimal approach to myotomy for patients with achalasia. Dr. Khashab makes the case for endoscopic myotomy, while Dr. Siwiec argues that surgical myotomy remains the gold standard. I hope that you will find this debate as useful and thought provoking as I did. As always, I welcome your comments and suggestions for future topics at [email protected].
Charles Kahi, MD, MS, AGAF, is a professor of medicine at Indiana University, Indianapolis. He is also an associate editor for GI & Hepatology News.
Endoscopic myotomy for achalasia is ready for prime time
BY MOUEN A. KHASHAB, MD
When I encounter a symptomatic patient with manometrically confirmed achalasia, I discuss three effective treatment modalities: pneumatic dilation (PD), peroral endoscopic myotomy (POEM), and laparoscopic Heller myotomy (LHM). I recommend against botulinum toxin injection and reserve it for patients who are not candidates for the aforementioned definitive therapies. I also present to the patient the current level I evidence from randomized, controlled trials (RCTs) comparing achalasia treatment modalities.
One landmark RCT reported comparative outcomes at 2 years following POEM and PD and found higher treatment success at the 2-year follow-up in the POEM group (92% vs. 54%; P < .001).1 Reflux esophagitis was observed significantly more frequently in patients treated with POEM (41% in the POEM group, of whom 35% were assigned Los Angeles grade A-B and 6% were assigned LA grade C versus 7% in the PD group, all of whom were assigned LA grade A; P = .002).1
Another milestone RCT included 221 patients and compared outcomes of POEM and LHM plus Dor fundoplication.2 Clinical success at the 2-year follow-up was observed in 83.0% of patients in the POEM group, and was noninferior to the LHM group (81.7%). Serious adverse events occurred in 2.7% of patients in the POEM group and in 7.3% of patients in the LHM group. Although 57% of patients in the POEM group and 20% of patients in the LHM group had reflux esophagitis as assessed by endoscopy at 3 months, the corresponding proportions were 44% and 29% at 24 months. Importantly, the rate of severe esophagitis was not different between both groups (6% vs. 3% at 3 months, and 5% vs. 6% at 24 months).2
I summarize these results by stating that POEM seems to be superior to PD and equivalent to LHM in terms of clinical success. Nonetheless, POEM also seems to be associated with increased risk of early gastroesophageal reflux disease.
POEM is now a ubiquitous procedure performed worldwide and is endorsed as a primary achalasia treatment by multiple society guidelines.3 It is a minimally invasive, effective, and safe therapeutic option for patients with all types of achalasia and is considered the treatment of choice for achalasia type III. POEM has also been shown to be effective in the treatment of spastic esophageal disorders (e.g. Jackhammer esophagus, diffuse esophageal spasm) and esophagogastric junction outflow obstruction. It can be performed in the endoscopy unit or operating theater either by experienced therapeutic endoscopists or surgical endoscopists in less than an hour. The procedure can be performed on an outpatient basis in appropriate individuals and allows tailoring the myotomy length to specific clinical scenarios. For example, patients with type III achalasia (and those with spastic esophageal disorders) typically require a long myotomy and that can be readily accomplished during POEM as opposed to LHM. POEM has also proven effective in children; octogenarians; and patients with sigmoid esophagus, epiphrenic diverticula, and those who had undergone prior interventions for achalasia, including LHM and PD. In experienced hands, the rate of adverse events is low and serious events are rare and occur in 0.5% of cases. Perforations/leakage are also uncommon and occur in 0.7% of patients. It is an incisionless procedure that eliminates the risk of wound infection and shortens postprocedural recovery. Patients are typically admitted for an overnight observation postprocedure, discharged home the following day, and back to activities of daily living (including work) within a few days. Postprocedural pain is minimal in most patients and narcotics are rarely needed. Resumption of a soft diet is carried out on the first postoperative day and normal diet 1 week later.
LHM is an established procedure with proven long-term efficacy in the treatment of achalasia. Nonetheless, it is invasive and requires placement of multiple trocars. The procedure is more time consuming than POEM and length of hospital stay can also be longer. This results in possibly higher cost than POEM. Importantly, recovery of dysphagia and resumption of normal diet is significantly delayed and is likely the result of the partial concomitant fundoplication procedure. Finally, LHM is not appropriate for the treatment of spastic esophageal disorders, including type III achalasia.
A major advantage of LHM plus partial fundoplication over POEM is the diminished risk of gastroesophageal reflux disease (GERD). However, this advantage seems short lived as the risk of GERD increases over time after surgery, likely because of the loosening of the wrap over time. From the New England Journal of Medicine paper mentioned earlier, it seems that the increased risk of GERD after POEM as compared with LHM diminishes over time.2 Importantly, it also appears that the rate of significant esophagitis (LA grade C-D) is similar between both procedures.2
In an effort to assess the long-term antireflux efficacy of surgical partial fundoplication, one study noted that 12% of 182 patients who had surgical myotomy with partial fundoplication continued to have occasional or continuous heartburn symptoms at a median of 18 years after surgery. Esophagitis and Barrett’s esophagus were found in 14.5% and 0.8% of patients, respectively. De novo esophageal adenocarcinoma has been reported after both POEM and LHM.4
Therefore, GERD and its complications can occur after any procedure that disrupts the lower esophageal sphincter (POEM, LHM, and PD) and postprocedural management of patients should include long-term testing and management of possible GERD. Different strategies have been proposed and include objective periodic testing for esophageal acid exposure, long-term and possible lifelong proton pump inhibitor use, and surveillance for long-term consequences of GER via periodic upper endoscopy.3
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. Approximately a third of post-POEM patients with clinically successful outcome and absence of reflux esophagitis on their first surveillance endoscopy eventually develop esophagitis at subsequent surveillance endoscopy.5
In summary, POEM has deservingly taken a prime time spot in the management of patients with achalasia. It is an efficient, efficacious and safe treatment modality that results in rapid resolution of achalasia symptoms in the majority of patients. Research should focus on technical modifications (e.g., short gastric myotomy; addition of endoscopic fundoplication) that reduce the incidence of postprocedural GERD.
References
1. Ponds FA et al. Effect of peroral endoscopic myotomy versus pneumatic dilation on symptom severity and treatment outcomes among treatment-naive patients with achalasia: A randomized clinical trial. JAMA. 2019;322:134-44.
2. Werner YB et al. Endoscopic or surgical myotomy in patients with idiopathic achalasia. N Engl J Med. 2019;381:2219-29.
3. Khashab MA et al. ASGE guideline on the management of achalasia. Gastrointest Endosc. 2020;91:213-27 e6.
4. Ichkhanian Y et al. Case of early Barrett cancer following peroral endoscopic myotomy. Gut. 2019;68:2107-110.
5. Werner YB et al. Clinical response to peroral endoscopic myotomy in patients with idiopathic achalasia at a minimum follow-up of 2 years. Gut. 2016;65:899-906.
Dr. Khashab is associate professor of medicine, director of therapeutic endoscopy, division of gastroenterology and hepatology, Johns Hopkins Hospital, Baltimore. He is a consultant for BSCI, Olympus, and Medtronic.
Heller myotomy is still the gold standard
BY ROBERT M. SIWIEC, MD
Achalasia is a rare, primary esophageal motor disorder characterized by ineffective relaxation of the lower esophageal sphincter (LES) and concomitant loss of esophageal peristalsis. High-resolution esophageal manometry has allowed for the diagnosis and classification of achalasia into relevant clinical subtypes which become important when discussing and considering treatment options. Confirmatory studies (e.g., timed barium esophagram) and provocative manometric maneuvers (e.g., upright swallows, rapid swallow sequence, and/or rapid drink challenge) can be helpful when distinguishing between true achalasia versus achalasia variants and esophagogastric junction outflow obstruction.
Treatment options only provide palliation by eliminating outflow obstruction caused by a nonrelaxing and often times hypertensive LES. Pharmacotherapy (e.g., oral nitrates, 5-phosphodiesterase inhibitors, anticholinergics) is the least effective option because of medication side effects and short-acting duration. I only consider it for patients who are either unwilling or unable to tolerate invasive therapies. Botulinum toxin injection into the LES can be considered in patients who are not good candidates for more definitive therapy with PD or myotomy (endoscopic or surgical). Although the success rates with botulinum toxin are comparable with PD and surgical myotomy, patients treated with botulinum toxin require retreatment. Furthermore, continued botulinum toxin injections can compromise tissue planes making myotomy complex and challenging.
During the 1970s and 1980s, PD was the primary treatment modality for achalasia. Surgical myotomy was reserved for patients who suffered a perforation during PD or developed recurrent symptoms after multiple dilations. Minimally invasive surgery (left thoracoscopic approach) for achalasia was first introduced in the early 1990s and was shown to be a feasible, safe, and effective procedure, becoming the primary treatment approach in most centers. Patients fared well; however, it was soon discovered that >50% had pathological reflux based on pH monitoring. A few centers then began to perform a Heller myotomy through a laparoscopic approach with the addition of a fundoplication resulting in significant reductions in pathological reflux by pH monitoring. Eventually, a seminal RCT confirmed the importance of fundoplication with laparoscopic Heller myotomy (LHM) – resolution of dysphagia was unaffected and pathological reflux was avoided in most patients.1 Overall, clinical success rates for LHM with fundoplication are typically >90% and reflux incidence rates <10% with the overall complication rate being about 5% with reported mortality <0.1%.
PD remains appealing in that it is cost effective and less invasive, compared with POEM and LHM. Initial success rates and short-term efficacy are comparable with LHM but unfortunately PD’s efficacy significantly wanes over time. POEM, introduced by Inoue et al. in 2010, is a novel endoscopic technique with an excellent safety profile that provides good symptom relief while avoiding abdominal wall scars for patients. It has been shown to have a distinct advantage in patients with type III achalasia by nature of the longer myotomy not achievable by LHM.2 POEM has seen increasing enthusiasm and acceptance as a standard treatment option for achalasia largely because of the fact that its safety and efficacy have been shown to be comparable and in most cases equal with LHM. However, in 2020, direct comparison with LHM is challenging given that the follow-up in the majority of studies is either short or incomplete. The most recent multicenter, randomized trial comparing POEM with LHM plus Dor fundoplication showed POEM’s noninferiority in controlling symptoms of achalasia, but only after a 24 month follow-up.3 A recent report included one of the largest cohorts of post-POEM patients (500), but the 36-month data were based on the follow-up of only 61 patients (about 12%).4
Once the muscle fibers of the LES are disrupted, reflux will occur in the majority of patients. Unlike LHM, no concomitant fundoplication is performed during POEM and this increases the incidence of GERD and its long-term sequelae including peptic strictures, Barrett’s esophagus, and adenocarcinoma. A meta-analysis from 2018 looked at published series of POEM and LHM with fundoplication and found that GERD symptoms were present in 19% of POEM patients, compared with 8.8% of LHM patients. Worse yet, esophagitis was seen in 29.4% of the POEM group and 7.6% of the LHM group, with more individuals in the POEM group also having abnormal acid exposure based on ambulatory pH monitoring (39.0% vs. 16.8%).5
Proponents of POEM will argue that proton pump inhibitors (PPIs) are the panacea for post-POEM GERD. Unfortunately, this approach has its own problems. PPIs are very effective at reducing acid secretion by parietal cells, but do not block reflux through an iatrogenically incompetent LES. The drumbeat of publications on potential complications from chronic PPI use has greatly contributed to patients’ reluctance to commit to long-term PPI use. Lastly, the first case of early Barrett’s cancer was recently reported in a patient 4 years post-POEM despite adherence to an aggressive antisecretory regimen (b.i.d. PPI and H2 blocker at bedtime).6 LHM with fundoplication significantly reduces the risk of pathological GERD and spares patients from committing to lifelong PPI therapy and routine endoscopic surveillance (appropriate interval yet to be determined) and needing to consider additional procedures (i.e., endoscopic or surgical fundoplication).
Despite POEM’s well established efficacy and safety, the development of post-POEM GERD is a major concern that has yet to be adequately addressed. A significant number of post-POEM patients with pathological reflux have asymptomatic and unrecognized GERD and current management and monitoring strategies for post-POEM GERD are anemic and poorly established. Without question, there are individual patients who are clearly better served with POEM (type III achalasia and other spastic esophageal disorders). However, as we continue to learn more about post-POEM GERD and how to better prevent, manage, and monitor it, LHM with fundoplication for the time being remains the tried-and-tested treatment option for patients with non–type III achalasia.
References
1. Richards WO et al. Heller myotomy versus Heller myotomy with Dor fundoplication for achalasia: A prospective randomized double-blind clinical trial. Ann Surg. 2004;240:405-12.
2. Podboy AJ et al. Long-term outcomes of peroral endoscopic myotomy compared to laparoscopic Heller myotomy for achalasia: A single-center experience. Surg Endosc. 2020. doi: 10.1007/s00464-020-07450-6.
3. Werner YB et al. Endoscopic or surgical myotomy in patients with idiopathic achalasia. N Engl J Med. 2019;381(23):2219-29.
4. Inoue H et al. Peroral endoscopic myotomy: A series of 500 patients. J Am Coll Surg. 2015;221:256-64.
5. Repici A et al. GERD after peroral endoscopic myotomy as compared with Heller’s myotomy with fundoplication: A systematic review with meta-analysis. Gastrointest Endosc. 2018;87(4):934-43.
6. Ichkhanian Y et al. Case of early Barrett cancer following peroral endoscopic myotomy. Gut. 2019;68:2107-10.
Dr. Siwiec is assistant professor of clinical medicine, division of gastroenterology and hepatology, GI motility and neurogastroenterology unit, Indiana University, Indianapolis. He has no conflicts of interest.
Dear colleagues and friends,
In this edition of Perspectives, Dr. Mouen Khashab and Dr. Robert Siwiec tackle an exciting and constantly evolving topic, which is the optimal approach to myotomy for patients with achalasia. Dr. Khashab makes the case for endoscopic myotomy, while Dr. Siwiec argues that surgical myotomy remains the gold standard. I hope that you will find this debate as useful and thought provoking as I did. As always, I welcome your comments and suggestions for future topics at [email protected].
Charles Kahi, MD, MS, AGAF, is a professor of medicine at Indiana University, Indianapolis. He is also an associate editor for GI & Hepatology News.
Endoscopic myotomy for achalasia is ready for prime time
BY MOUEN A. KHASHAB, MD
When I encounter a symptomatic patient with manometrically confirmed achalasia, I discuss three effective treatment modalities: pneumatic dilation (PD), peroral endoscopic myotomy (POEM), and laparoscopic Heller myotomy (LHM). I recommend against botulinum toxin injection and reserve it for patients who are not candidates for the aforementioned definitive therapies. I also present to the patient the current level I evidence from randomized, controlled trials (RCTs) comparing achalasia treatment modalities.
One landmark RCT reported comparative outcomes at 2 years following POEM and PD and found higher treatment success at the 2-year follow-up in the POEM group (92% vs. 54%; P < .001).1 Reflux esophagitis was observed significantly more frequently in patients treated with POEM (41% in the POEM group, of whom 35% were assigned Los Angeles grade A-B and 6% were assigned LA grade C versus 7% in the PD group, all of whom were assigned LA grade A; P = .002).1
Another milestone RCT included 221 patients and compared outcomes of POEM and LHM plus Dor fundoplication.2 Clinical success at the 2-year follow-up was observed in 83.0% of patients in the POEM group, and was noninferior to the LHM group (81.7%). Serious adverse events occurred in 2.7% of patients in the POEM group and in 7.3% of patients in the LHM group. Although 57% of patients in the POEM group and 20% of patients in the LHM group had reflux esophagitis as assessed by endoscopy at 3 months, the corresponding proportions were 44% and 29% at 24 months. Importantly, the rate of severe esophagitis was not different between both groups (6% vs. 3% at 3 months, and 5% vs. 6% at 24 months).2
I summarize these results by stating that POEM seems to be superior to PD and equivalent to LHM in terms of clinical success. Nonetheless, POEM also seems to be associated with increased risk of early gastroesophageal reflux disease.
POEM is now a ubiquitous procedure performed worldwide and is endorsed as a primary achalasia treatment by multiple society guidelines.3 It is a minimally invasive, effective, and safe therapeutic option for patients with all types of achalasia and is considered the treatment of choice for achalasia type III. POEM has also been shown to be effective in the treatment of spastic esophageal disorders (e.g. Jackhammer esophagus, diffuse esophageal spasm) and esophagogastric junction outflow obstruction. It can be performed in the endoscopy unit or operating theater either by experienced therapeutic endoscopists or surgical endoscopists in less than an hour. The procedure can be performed on an outpatient basis in appropriate individuals and allows tailoring the myotomy length to specific clinical scenarios. For example, patients with type III achalasia (and those with spastic esophageal disorders) typically require a long myotomy and that can be readily accomplished during POEM as opposed to LHM. POEM has also proven effective in children; octogenarians; and patients with sigmoid esophagus, epiphrenic diverticula, and those who had undergone prior interventions for achalasia, including LHM and PD. In experienced hands, the rate of adverse events is low and serious events are rare and occur in 0.5% of cases. Perforations/leakage are also uncommon and occur in 0.7% of patients. It is an incisionless procedure that eliminates the risk of wound infection and shortens postprocedural recovery. Patients are typically admitted for an overnight observation postprocedure, discharged home the following day, and back to activities of daily living (including work) within a few days. Postprocedural pain is minimal in most patients and narcotics are rarely needed. Resumption of a soft diet is carried out on the first postoperative day and normal diet 1 week later.
LHM is an established procedure with proven long-term efficacy in the treatment of achalasia. Nonetheless, it is invasive and requires placement of multiple trocars. The procedure is more time consuming than POEM and length of hospital stay can also be longer. This results in possibly higher cost than POEM. Importantly, recovery of dysphagia and resumption of normal diet is significantly delayed and is likely the result of the partial concomitant fundoplication procedure. Finally, LHM is not appropriate for the treatment of spastic esophageal disorders, including type III achalasia.
A major advantage of LHM plus partial fundoplication over POEM is the diminished risk of gastroesophageal reflux disease (GERD). However, this advantage seems short lived as the risk of GERD increases over time after surgery, likely because of the loosening of the wrap over time. From the New England Journal of Medicine paper mentioned earlier, it seems that the increased risk of GERD after POEM as compared with LHM diminishes over time.2 Importantly, it also appears that the rate of significant esophagitis (LA grade C-D) is similar between both procedures.2
In an effort to assess the long-term antireflux efficacy of surgical partial fundoplication, one study noted that 12% of 182 patients who had surgical myotomy with partial fundoplication continued to have occasional or continuous heartburn symptoms at a median of 18 years after surgery. Esophagitis and Barrett’s esophagus were found in 14.5% and 0.8% of patients, respectively. De novo esophageal adenocarcinoma has been reported after both POEM and LHM.4
Therefore, GERD and its complications can occur after any procedure that disrupts the lower esophageal sphincter (POEM, LHM, and PD) and postprocedural management of patients should include long-term testing and management of possible GERD. Different strategies have been proposed and include objective periodic testing for esophageal acid exposure, long-term and possible lifelong proton pump inhibitor use, and surveillance for long-term consequences of GER via periodic upper endoscopy.3
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. Approximately a third of post-POEM patients with clinically successful outcome and absence of reflux esophagitis on their first surveillance endoscopy eventually develop esophagitis at subsequent surveillance endoscopy.5
In summary, POEM has deservingly taken a prime time spot in the management of patients with achalasia. It is an efficient, efficacious and safe treatment modality that results in rapid resolution of achalasia symptoms in the majority of patients. Research should focus on technical modifications (e.g., short gastric myotomy; addition of endoscopic fundoplication) that reduce the incidence of postprocedural GERD.
References
1. Ponds FA et al. Effect of peroral endoscopic myotomy versus pneumatic dilation on symptom severity and treatment outcomes among treatment-naive patients with achalasia: A randomized clinical trial. JAMA. 2019;322:134-44.
2. Werner YB et al. Endoscopic or surgical myotomy in patients with idiopathic achalasia. N Engl J Med. 2019;381:2219-29.
3. Khashab MA et al. ASGE guideline on the management of achalasia. Gastrointest Endosc. 2020;91:213-27 e6.
4. Ichkhanian Y et al. Case of early Barrett cancer following peroral endoscopic myotomy. Gut. 2019;68:2107-110.
5. Werner YB et al. Clinical response to peroral endoscopic myotomy in patients with idiopathic achalasia at a minimum follow-up of 2 years. Gut. 2016;65:899-906.
Dr. Khashab is associate professor of medicine, director of therapeutic endoscopy, division of gastroenterology and hepatology, Johns Hopkins Hospital, Baltimore. He is a consultant for BSCI, Olympus, and Medtronic.
Heller myotomy is still the gold standard
BY ROBERT M. SIWIEC, MD
Achalasia is a rare, primary esophageal motor disorder characterized by ineffective relaxation of the lower esophageal sphincter (LES) and concomitant loss of esophageal peristalsis. High-resolution esophageal manometry has allowed for the diagnosis and classification of achalasia into relevant clinical subtypes which become important when discussing and considering treatment options. Confirmatory studies (e.g., timed barium esophagram) and provocative manometric maneuvers (e.g., upright swallows, rapid swallow sequence, and/or rapid drink challenge) can be helpful when distinguishing between true achalasia versus achalasia variants and esophagogastric junction outflow obstruction.
Treatment options only provide palliation by eliminating outflow obstruction caused by a nonrelaxing and often times hypertensive LES. Pharmacotherapy (e.g., oral nitrates, 5-phosphodiesterase inhibitors, anticholinergics) is the least effective option because of medication side effects and short-acting duration. I only consider it for patients who are either unwilling or unable to tolerate invasive therapies. Botulinum toxin injection into the LES can be considered in patients who are not good candidates for more definitive therapy with PD or myotomy (endoscopic or surgical). Although the success rates with botulinum toxin are comparable with PD and surgical myotomy, patients treated with botulinum toxin require retreatment. Furthermore, continued botulinum toxin injections can compromise tissue planes making myotomy complex and challenging.
During the 1970s and 1980s, PD was the primary treatment modality for achalasia. Surgical myotomy was reserved for patients who suffered a perforation during PD or developed recurrent symptoms after multiple dilations. Minimally invasive surgery (left thoracoscopic approach) for achalasia was first introduced in the early 1990s and was shown to be a feasible, safe, and effective procedure, becoming the primary treatment approach in most centers. Patients fared well; however, it was soon discovered that >50% had pathological reflux based on pH monitoring. A few centers then began to perform a Heller myotomy through a laparoscopic approach with the addition of a fundoplication resulting in significant reductions in pathological reflux by pH monitoring. Eventually, a seminal RCT confirmed the importance of fundoplication with laparoscopic Heller myotomy (LHM) – resolution of dysphagia was unaffected and pathological reflux was avoided in most patients.1 Overall, clinical success rates for LHM with fundoplication are typically >90% and reflux incidence rates <10% with the overall complication rate being about 5% with reported mortality <0.1%.
PD remains appealing in that it is cost effective and less invasive, compared with POEM and LHM. Initial success rates and short-term efficacy are comparable with LHM but unfortunately PD’s efficacy significantly wanes over time. POEM, introduced by Inoue et al. in 2010, is a novel endoscopic technique with an excellent safety profile that provides good symptom relief while avoiding abdominal wall scars for patients. It has been shown to have a distinct advantage in patients with type III achalasia by nature of the longer myotomy not achievable by LHM.2 POEM has seen increasing enthusiasm and acceptance as a standard treatment option for achalasia largely because of the fact that its safety and efficacy have been shown to be comparable and in most cases equal with LHM. However, in 2020, direct comparison with LHM is challenging given that the follow-up in the majority of studies is either short or incomplete. The most recent multicenter, randomized trial comparing POEM with LHM plus Dor fundoplication showed POEM’s noninferiority in controlling symptoms of achalasia, but only after a 24 month follow-up.3 A recent report included one of the largest cohorts of post-POEM patients (500), but the 36-month data were based on the follow-up of only 61 patients (about 12%).4
Once the muscle fibers of the LES are disrupted, reflux will occur in the majority of patients. Unlike LHM, no concomitant fundoplication is performed during POEM and this increases the incidence of GERD and its long-term sequelae including peptic strictures, Barrett’s esophagus, and adenocarcinoma. A meta-analysis from 2018 looked at published series of POEM and LHM with fundoplication and found that GERD symptoms were present in 19% of POEM patients, compared with 8.8% of LHM patients. Worse yet, esophagitis was seen in 29.4% of the POEM group and 7.6% of the LHM group, with more individuals in the POEM group also having abnormal acid exposure based on ambulatory pH monitoring (39.0% vs. 16.8%).5
Proponents of POEM will argue that proton pump inhibitors (PPIs) are the panacea for post-POEM GERD. Unfortunately, this approach has its own problems. PPIs are very effective at reducing acid secretion by parietal cells, but do not block reflux through an iatrogenically incompetent LES. The drumbeat of publications on potential complications from chronic PPI use has greatly contributed to patients’ reluctance to commit to long-term PPI use. Lastly, the first case of early Barrett’s cancer was recently reported in a patient 4 years post-POEM despite adherence to an aggressive antisecretory regimen (b.i.d. PPI and H2 blocker at bedtime).6 LHM with fundoplication significantly reduces the risk of pathological GERD and spares patients from committing to lifelong PPI therapy and routine endoscopic surveillance (appropriate interval yet to be determined) and needing to consider additional procedures (i.e., endoscopic or surgical fundoplication).
Despite POEM’s well established efficacy and safety, the development of post-POEM GERD is a major concern that has yet to be adequately addressed. A significant number of post-POEM patients with pathological reflux have asymptomatic and unrecognized GERD and current management and monitoring strategies for post-POEM GERD are anemic and poorly established. Without question, there are individual patients who are clearly better served with POEM (type III achalasia and other spastic esophageal disorders). However, as we continue to learn more about post-POEM GERD and how to better prevent, manage, and monitor it, LHM with fundoplication for the time being remains the tried-and-tested treatment option for patients with non–type III achalasia.
References
1. Richards WO et al. Heller myotomy versus Heller myotomy with Dor fundoplication for achalasia: A prospective randomized double-blind clinical trial. Ann Surg. 2004;240:405-12.
2. Podboy AJ et al. Long-term outcomes of peroral endoscopic myotomy compared to laparoscopic Heller myotomy for achalasia: A single-center experience. Surg Endosc. 2020. doi: 10.1007/s00464-020-07450-6.
3. Werner YB et al. Endoscopic or surgical myotomy in patients with idiopathic achalasia. N Engl J Med. 2019;381(23):2219-29.
4. Inoue H et al. Peroral endoscopic myotomy: A series of 500 patients. J Am Coll Surg. 2015;221:256-64.
5. Repici A et al. GERD after peroral endoscopic myotomy as compared with Heller’s myotomy with fundoplication: A systematic review with meta-analysis. Gastrointest Endosc. 2018;87(4):934-43.
6. Ichkhanian Y et al. Case of early Barrett cancer following peroral endoscopic myotomy. Gut. 2019;68:2107-10.
Dr. Siwiec is assistant professor of clinical medicine, division of gastroenterology and hepatology, GI motility and neurogastroenterology unit, Indiana University, Indianapolis. He has no conflicts of interest.
Dear colleagues and friends,
In this edition of Perspectives, Dr. Mouen Khashab and Dr. Robert Siwiec tackle an exciting and constantly evolving topic, which is the optimal approach to myotomy for patients with achalasia. Dr. Khashab makes the case for endoscopic myotomy, while Dr. Siwiec argues that surgical myotomy remains the gold standard. I hope that you will find this debate as useful and thought provoking as I did. As always, I welcome your comments and suggestions for future topics at [email protected].
Charles Kahi, MD, MS, AGAF, is a professor of medicine at Indiana University, Indianapolis. He is also an associate editor for GI & Hepatology News.
Endoscopic myotomy for achalasia is ready for prime time
BY MOUEN A. KHASHAB, MD
When I encounter a symptomatic patient with manometrically confirmed achalasia, I discuss three effective treatment modalities: pneumatic dilation (PD), peroral endoscopic myotomy (POEM), and laparoscopic Heller myotomy (LHM). I recommend against botulinum toxin injection and reserve it for patients who are not candidates for the aforementioned definitive therapies. I also present to the patient the current level I evidence from randomized, controlled trials (RCTs) comparing achalasia treatment modalities.
One landmark RCT reported comparative outcomes at 2 years following POEM and PD and found higher treatment success at the 2-year follow-up in the POEM group (92% vs. 54%; P < .001).1 Reflux esophagitis was observed significantly more frequently in patients treated with POEM (41% in the POEM group, of whom 35% were assigned Los Angeles grade A-B and 6% were assigned LA grade C versus 7% in the PD group, all of whom were assigned LA grade A; P = .002).1
Another milestone RCT included 221 patients and compared outcomes of POEM and LHM plus Dor fundoplication.2 Clinical success at the 2-year follow-up was observed in 83.0% of patients in the POEM group, and was noninferior to the LHM group (81.7%). Serious adverse events occurred in 2.7% of patients in the POEM group and in 7.3% of patients in the LHM group. Although 57% of patients in the POEM group and 20% of patients in the LHM group had reflux esophagitis as assessed by endoscopy at 3 months, the corresponding proportions were 44% and 29% at 24 months. Importantly, the rate of severe esophagitis was not different between both groups (6% vs. 3% at 3 months, and 5% vs. 6% at 24 months).2
I summarize these results by stating that POEM seems to be superior to PD and equivalent to LHM in terms of clinical success. Nonetheless, POEM also seems to be associated with increased risk of early gastroesophageal reflux disease.
POEM is now a ubiquitous procedure performed worldwide and is endorsed as a primary achalasia treatment by multiple society guidelines.3 It is a minimally invasive, effective, and safe therapeutic option for patients with all types of achalasia and is considered the treatment of choice for achalasia type III. POEM has also been shown to be effective in the treatment of spastic esophageal disorders (e.g. Jackhammer esophagus, diffuse esophageal spasm) and esophagogastric junction outflow obstruction. It can be performed in the endoscopy unit or operating theater either by experienced therapeutic endoscopists or surgical endoscopists in less than an hour. The procedure can be performed on an outpatient basis in appropriate individuals and allows tailoring the myotomy length to specific clinical scenarios. For example, patients with type III achalasia (and those with spastic esophageal disorders) typically require a long myotomy and that can be readily accomplished during POEM as opposed to LHM. POEM has also proven effective in children; octogenarians; and patients with sigmoid esophagus, epiphrenic diverticula, and those who had undergone prior interventions for achalasia, including LHM and PD. In experienced hands, the rate of adverse events is low and serious events are rare and occur in 0.5% of cases. Perforations/leakage are also uncommon and occur in 0.7% of patients. It is an incisionless procedure that eliminates the risk of wound infection and shortens postprocedural recovery. Patients are typically admitted for an overnight observation postprocedure, discharged home the following day, and back to activities of daily living (including work) within a few days. Postprocedural pain is minimal in most patients and narcotics are rarely needed. Resumption of a soft diet is carried out on the first postoperative day and normal diet 1 week later.
LHM is an established procedure with proven long-term efficacy in the treatment of achalasia. Nonetheless, it is invasive and requires placement of multiple trocars. The procedure is more time consuming than POEM and length of hospital stay can also be longer. This results in possibly higher cost than POEM. Importantly, recovery of dysphagia and resumption of normal diet is significantly delayed and is likely the result of the partial concomitant fundoplication procedure. Finally, LHM is not appropriate for the treatment of spastic esophageal disorders, including type III achalasia.
A major advantage of LHM plus partial fundoplication over POEM is the diminished risk of gastroesophageal reflux disease (GERD). However, this advantage seems short lived as the risk of GERD increases over time after surgery, likely because of the loosening of the wrap over time. From the New England Journal of Medicine paper mentioned earlier, it seems that the increased risk of GERD after POEM as compared with LHM diminishes over time.2 Importantly, it also appears that the rate of significant esophagitis (LA grade C-D) is similar between both procedures.2
In an effort to assess the long-term antireflux efficacy of surgical partial fundoplication, one study noted that 12% of 182 patients who had surgical myotomy with partial fundoplication continued to have occasional or continuous heartburn symptoms at a median of 18 years after surgery. Esophagitis and Barrett’s esophagus were found in 14.5% and 0.8% of patients, respectively. De novo esophageal adenocarcinoma has been reported after both POEM and LHM.4
Therefore, GERD and its complications can occur after any procedure that disrupts the lower esophageal sphincter (POEM, LHM, and PD) and postprocedural management of patients should include long-term testing and management of possible GERD. Different strategies have been proposed and include objective periodic testing for esophageal acid exposure, long-term and possible lifelong proton pump inhibitor use, and surveillance for long-term consequences of GER via periodic upper endoscopy.3
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. Approximately a third of post-POEM patients with clinically successful outcome and absence of reflux esophagitis on their first surveillance endoscopy eventually develop esophagitis at subsequent surveillance endoscopy.5
In summary, POEM has deservingly taken a prime time spot in the management of patients with achalasia. It is an efficient, efficacious and safe treatment modality that results in rapid resolution of achalasia symptoms in the majority of patients. Research should focus on technical modifications (e.g., short gastric myotomy; addition of endoscopic fundoplication) that reduce the incidence of postprocedural GERD.
References
1. Ponds FA et al. Effect of peroral endoscopic myotomy versus pneumatic dilation on symptom severity and treatment outcomes among treatment-naive patients with achalasia: A randomized clinical trial. JAMA. 2019;322:134-44.
2. Werner YB et al. Endoscopic or surgical myotomy in patients with idiopathic achalasia. N Engl J Med. 2019;381:2219-29.
3. Khashab MA et al. ASGE guideline on the management of achalasia. Gastrointest Endosc. 2020;91:213-27 e6.
4. Ichkhanian Y et al. Case of early Barrett cancer following peroral endoscopic myotomy. Gut. 2019;68:2107-110.
5. Werner YB et al. Clinical response to peroral endoscopic myotomy in patients with idiopathic achalasia at a minimum follow-up of 2 years. Gut. 2016;65:899-906.
Dr. Khashab is associate professor of medicine, director of therapeutic endoscopy, division of gastroenterology and hepatology, Johns Hopkins Hospital, Baltimore. He is a consultant for BSCI, Olympus, and Medtronic.
Heller myotomy is still the gold standard
BY ROBERT M. SIWIEC, MD
Achalasia is a rare, primary esophageal motor disorder characterized by ineffective relaxation of the lower esophageal sphincter (LES) and concomitant loss of esophageal peristalsis. High-resolution esophageal manometry has allowed for the diagnosis and classification of achalasia into relevant clinical subtypes which become important when discussing and considering treatment options. Confirmatory studies (e.g., timed barium esophagram) and provocative manometric maneuvers (e.g., upright swallows, rapid swallow sequence, and/or rapid drink challenge) can be helpful when distinguishing between true achalasia versus achalasia variants and esophagogastric junction outflow obstruction.
Treatment options only provide palliation by eliminating outflow obstruction caused by a nonrelaxing and often times hypertensive LES. Pharmacotherapy (e.g., oral nitrates, 5-phosphodiesterase inhibitors, anticholinergics) is the least effective option because of medication side effects and short-acting duration. I only consider it for patients who are either unwilling or unable to tolerate invasive therapies. Botulinum toxin injection into the LES can be considered in patients who are not good candidates for more definitive therapy with PD or myotomy (endoscopic or surgical). Although the success rates with botulinum toxin are comparable with PD and surgical myotomy, patients treated with botulinum toxin require retreatment. Furthermore, continued botulinum toxin injections can compromise tissue planes making myotomy complex and challenging.
During the 1970s and 1980s, PD was the primary treatment modality for achalasia. Surgical myotomy was reserved for patients who suffered a perforation during PD or developed recurrent symptoms after multiple dilations. Minimally invasive surgery (left thoracoscopic approach) for achalasia was first introduced in the early 1990s and was shown to be a feasible, safe, and effective procedure, becoming the primary treatment approach in most centers. Patients fared well; however, it was soon discovered that >50% had pathological reflux based on pH monitoring. A few centers then began to perform a Heller myotomy through a laparoscopic approach with the addition of a fundoplication resulting in significant reductions in pathological reflux by pH monitoring. Eventually, a seminal RCT confirmed the importance of fundoplication with laparoscopic Heller myotomy (LHM) – resolution of dysphagia was unaffected and pathological reflux was avoided in most patients.1 Overall, clinical success rates for LHM with fundoplication are typically >90% and reflux incidence rates <10% with the overall complication rate being about 5% with reported mortality <0.1%.
PD remains appealing in that it is cost effective and less invasive, compared with POEM and LHM. Initial success rates and short-term efficacy are comparable with LHM but unfortunately PD’s efficacy significantly wanes over time. POEM, introduced by Inoue et al. in 2010, is a novel endoscopic technique with an excellent safety profile that provides good symptom relief while avoiding abdominal wall scars for patients. It has been shown to have a distinct advantage in patients with type III achalasia by nature of the longer myotomy not achievable by LHM.2 POEM has seen increasing enthusiasm and acceptance as a standard treatment option for achalasia largely because of the fact that its safety and efficacy have been shown to be comparable and in most cases equal with LHM. However, in 2020, direct comparison with LHM is challenging given that the follow-up in the majority of studies is either short or incomplete. The most recent multicenter, randomized trial comparing POEM with LHM plus Dor fundoplication showed POEM’s noninferiority in controlling symptoms of achalasia, but only after a 24 month follow-up.3 A recent report included one of the largest cohorts of post-POEM patients (500), but the 36-month data were based on the follow-up of only 61 patients (about 12%).4
Once the muscle fibers of the LES are disrupted, reflux will occur in the majority of patients. Unlike LHM, no concomitant fundoplication is performed during POEM and this increases the incidence of GERD and its long-term sequelae including peptic strictures, Barrett’s esophagus, and adenocarcinoma. A meta-analysis from 2018 looked at published series of POEM and LHM with fundoplication and found that GERD symptoms were present in 19% of POEM patients, compared with 8.8% of LHM patients. Worse yet, esophagitis was seen in 29.4% of the POEM group and 7.6% of the LHM group, with more individuals in the POEM group also having abnormal acid exposure based on ambulatory pH monitoring (39.0% vs. 16.8%).5
Proponents of POEM will argue that proton pump inhibitors (PPIs) are the panacea for post-POEM GERD. Unfortunately, this approach has its own problems. PPIs are very effective at reducing acid secretion by parietal cells, but do not block reflux through an iatrogenically incompetent LES. The drumbeat of publications on potential complications from chronic PPI use has greatly contributed to patients’ reluctance to commit to long-term PPI use. Lastly, the first case of early Barrett’s cancer was recently reported in a patient 4 years post-POEM despite adherence to an aggressive antisecretory regimen (b.i.d. PPI and H2 blocker at bedtime).6 LHM with fundoplication significantly reduces the risk of pathological GERD and spares patients from committing to lifelong PPI therapy and routine endoscopic surveillance (appropriate interval yet to be determined) and needing to consider additional procedures (i.e., endoscopic or surgical fundoplication).
Despite POEM’s well established efficacy and safety, the development of post-POEM GERD is a major concern that has yet to be adequately addressed. A significant number of post-POEM patients with pathological reflux have asymptomatic and unrecognized GERD and current management and monitoring strategies for post-POEM GERD are anemic and poorly established. Without question, there are individual patients who are clearly better served with POEM (type III achalasia and other spastic esophageal disorders). However, as we continue to learn more about post-POEM GERD and how to better prevent, manage, and monitor it, LHM with fundoplication for the time being remains the tried-and-tested treatment option for patients with non–type III achalasia.
References
1. Richards WO et al. Heller myotomy versus Heller myotomy with Dor fundoplication for achalasia: A prospective randomized double-blind clinical trial. Ann Surg. 2004;240:405-12.
2. Podboy AJ et al. Long-term outcomes of peroral endoscopic myotomy compared to laparoscopic Heller myotomy for achalasia: A single-center experience. Surg Endosc. 2020. doi: 10.1007/s00464-020-07450-6.
3. Werner YB et al. Endoscopic or surgical myotomy in patients with idiopathic achalasia. N Engl J Med. 2019;381(23):2219-29.
4. Inoue H et al. Peroral endoscopic myotomy: A series of 500 patients. J Am Coll Surg. 2015;221:256-64.
5. Repici A et al. GERD after peroral endoscopic myotomy as compared with Heller’s myotomy with fundoplication: A systematic review with meta-analysis. Gastrointest Endosc. 2018;87(4):934-43.
6. Ichkhanian Y et al. Case of early Barrett cancer following peroral endoscopic myotomy. Gut. 2019;68:2107-10.
Dr. Siwiec is assistant professor of clinical medicine, division of gastroenterology and hepatology, GI motility and neurogastroenterology unit, Indiana University, Indianapolis. He has no conflicts of interest.