Gastric per-oral endoscopic myotomy:Indications,technique,results and comparison with surgical approach

Gastroparesis is a chronic disease of the stomach that causes a delayed gastric emptying,without the presence of a stenosis.For 30 years the authors identified pylorospasm as one of the most important pathophysiological mechanisms determining gastroparesis.Studies with EndoFLIP,a device that assesses pyloric distensibility,increased the knowledge about pylorospasm.Based on this data,several pyloric-targeted therapies were developed to treat refractory gastroparesis:Surgical pyloroplasty and endoscopic approach,such as pyloric injection of botulinum and pyloric stenting.Notwithstanding,the success of most of these techniques is still not complete.In 2013,the first human gastric per-oral endoscopic myotomy(GPOEM)was performed.It was inspired by the POEM technique,with a similar dissection method,that allows pyloromyotomy.Therapeutical results of GPOEM are similar to surgical approach in term of clinical success,adverse events and post-surgical pain.In the last 8 years GPOEM has gained the attention of the scientific community,as a minimally invasive technique with high rate of clinical success,quickly prevailing as a promising therapy for gastroparesis.Not surprisingly,in referral centers,its technical success rate is 100%.One of the main goals of recent studies is to identify those patients that will respond better to the therapies targeted on pylorus and to choose the better approach for each patient.

Gastric per-oral endoscopic myotomy: Current status and future directions

Gastroparesis, or symptomatic delayed gastric emptying in the absence of mechanical obstruction, is a challenging and increasingly identified syndrome. Medical options are limited and the only medication approved by the Food and Drug Administration for treatment of gastroparesis is metoclopramide, although other agents are frequently used off label. With this caveat, first-line treatments for gastroparesis include dietary modifications, antiemetics and promotility agents, although these therapies are limited by suboptimal efficacy and significant medication side effects. Treatment of patients that fail first-line treatments represents a significant therapeutic challenge. Recent advances in endoscopic techniques have led to the development of a promising novel endoscopic therapy for gastroparesis via endoscopic pyloromyotomy, also referred to as gastric per-oral endoscopic myotomy or per-oral endoscopic pyloromyotomy. The aim of this article is to review the technical aspects of the per-oral endoscopic myotomy procedure for the treatment of gastroparesis, provide an overview of the currently published literature, and outline potential next directions for the field.

Prediction,prevention and management of gastroesophageal reflux after per-oral endoscopic myotomy:An update

Achalasia cardia,the most prevalent primary esophageal motility disorder,is predominantly characterized by symptoms of dysphagia and regurgitation.The principal therapeutic approaches for achalasia encompass pneumatic dilatation(PD),Heller's myotomy,and the more recent per-oral endoscopic myotomy(POEM).POEM has been substantiated as a safe and efficacious modality for the management of achalasia.Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy,the incidence of gastroesophageal reflux disease(GERD)following POEM is notably higher than with the aforementioned techniques.While symptomatic reflux post-POEM is relatively infrequent,the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications.Contemporary advancements in the field have enhanced our comprehension of the risk factors,diagnostic methodologies,preventative strategies,and therapeutic management of GERD subsequent to POEM.This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux,potential modifications in the POEM technique to mitigate GERD risk,and the strategies for managing reflux following POEM.

Gastroesophageal reflux after per-oral endoscopic myotomy:Management literature

In this editorial,we respond to a review article by Nabi et al,in which the authors discussed gastroesophageal reflux(GER)following peroral endoscopic myotomy(POEM).POEM is presently the primary therapeutic option for achalasia,which is both safe and effective.A few adverse effects were documented after POEM,including GER.The diagnostic criteria were not clear enough because approximately 60%of patients have a long acid exposure time,while only 10%experience reflux symptoms.Multiple predictors of high disease incidence have been identified,including old age,female sex,obesity,and a baseline lower esophageal sphincter pressure of less than 45 mmHg.Some technical steps during the procedure,such as a lengthy or full-thickness myotomy,may further enhance the risk.Proton pump inhibitors are currently the first line of treatment.Emerging voices are increasingly advocating for the routine combining of POEM with an endoscopic fundoplication method,such as peroral endoscopic fundoplication or transoral incisionless fundoplication.However,more research is necessary to determine the safety and effectiveness of these procedures in the long term for patients who have undergone them.

Applications of gastric peroral endoscopic myotomy in the treatment of upper gastrointestinal tract disease

Gastric peroral endoscopic myotomy(G-POME)is an emerging minimally invasive endoscopic technique involving the establishment of a submucosal tun-nel around the pyloric sphincter.In 2013,Khashab et al used G-POME for the first time in the treatment of gastroparesis with enhanced therapeutic efficacy,prov-iding a new direction for the treatment of gastroparesis.With the recent and rapid development of G-POME therapy technology,progress has been made in the treatment of gastroparesis and other upper digestive tract diseases,such as congenital hypertrophic pyloric stenosis and gastric sleeve stricture,with G-POME.This article reviews the research progress and future prospects of G-POME for the treatment of upper digestive tract gastrointestinal diseases.

Per-oral endoscopic myotomy is safe and effective for pediatric patients with achalasia:A long-term follow-up study

BACKGROUND Per-oral endoscopic myotomy(POEM)is emerging as a prefer treatment option for pediatric achalasia.However,data are limited on the long-term efficacy of POEM in children and adolescents with achalasia.AIM To evaluate the safety and long-term efficacy of POEM for pediatric patients with achalasia and compare those outcomes with adult patients.METHODS This retrospective cohort study was conducted in patients with achalasia who underwent POEM.Patients aged under 18 years were included in the pediatric group;patients aged between 18 to 65 years who underwent POEM in the same period were assigned to the control group.For investigation of long-term followup,the pediatric group were matched with patients from the control group in a 1:1 ratio.The procedure-related parameters,adverse events,clinical success,gastroesophageal reflux disease(GERD)after POEM,and quality of life(QoL)were evaluated.RESULTS From January 2012 to March 2020,POEM was performed in 1025 patients aged under 65 years old(48 in the pediatric group,1025 in the control group).No significant differences were observed in the occurrence of POEM complications between the two groups(14.6%vs 14.6%;P=0.99).Among the 34 pediatric patients(70.8%)who underwent follow-up for 5.7 years(range 2.6-10.6 years),clinical success was achieved in 35 patients(35/36;97.2%).No differences were observed in post-POEM GERD occurrence(17.6%vs 35.3%;P=0.10).QoL was significantly improved in both groups after POEM.CONCLUSION POEM is safe and effective for pediatric patients with achalasia.It can achieve significant symptoms relief and improve QoL.

Gastroesophageal reflux following peroral endoscopic myotomy for achalasia:Bumps in the road to success

Achalasia can significantly impair the quality of life.The clinical presentation typically includes dysphagia to both solids and liquids,chest pain,and regurgitation.Diagnosis can be delayed in patients with atypical presentations,and they might receive a wrong diagnosis,such as gastroesophageal reflux disease(GERD),owing to overlapping symptoms of both disorders.Although the cause of achalasia is poorly understood,its impact on the motility of the esophagus and gastroesophageal junction is well established.Several treatment modalities have been utilized,with the most common being surgical Heller myotomy with concomitant fundoplication and pneumatic balloon dilatation.Recently,peroral endoscopic myotomy(POEM)has gained popularity as an effective treatment for achalasia,despite a relatively high incidence of GERD occurring after treatment compared to other modalities.The magnitude of post-POEM GERD depends on its definition and is influenced by patient and procedure-related factors.The longterm sequelae of post-POEM GERD are yet to be determined,but it appears to have a benign course and is usually manageable with clinically available modalities.Identifying risk factors for post-POEM GERD and modifying the POEM procedure in selected patients may improve the overall success of this technique.

Recent progress of gastroesophageal reflux after endoscopic myotomy

Per-oral endoscopic myotomy(POEM)is an innovative minimally invasive technique and has emerged as the preferred modality for treating achalasia and spastic esophageal disorders in numerous specialized centers worldwide.Gastroesophageal reflux(GER)is a common complication following POEM procedures.Recently,an article in the World Journal of Gastroenterology,providing a comprehensive update on post-POEM GER.In this article,the authors present novel insights and strategies that offer valuable implications for endoscopy.

Per-oral endoscopic myotomy for achalasia: An American perspective

Achalasia is an uncommon esophageal motility disorder characterized by the selective loss of enteric neurons leading to absence of peristalsis and impaired relaxation of the lower esophageal sphincter.Per-oral endoscopic myotomy(POEM) is a novel modality for the treatment of achalasia performed by gastroenterologists and surgeons.It represents a natural orifice transluminal endoscopic surgery(NOTES) approach to Heller myotomy.POEM has the minimal invasiveness of an endoscopic procedure that can duplicate results of the surgical Heller myotomy.POEM is conceptually similar to a surgical myotomy without the inherent external incisions and post-operative care associated with surgery.Initial high success and low complications rates promise a great future for this technique.In fact,POEM has been successfully performed on patients with end-stage achalasia as an initial treatment reserving esophagectomy for those without good response.The volume of POEMs performed worldwide has grown exponentially.In fact,surgeons who have performed Heller myotomy have embraced POEM as the preferred intervention for achalasia.However,the niche of POEM remains to be defined and long term results are awaited.We describe our experience with POEM having performed the first POEM outside of Japan in 2009,the evolution of our technique,and give our perspective on its future.

Triple A syndrome-related achalasia treated by per-oral endoscopic myotomy:Three case reports

BACKGROUND Triple A syndrome is a rare autosomal recessive disease characterized by adrenocorticotropic hormone-resistant adrenal insufficiency,alacrima and achalasia.In the last 5 years,per-oral endoscopic myotomy(POEM)has proved highly successful in treating primary achalasia over the long term,but its long-term performance has not been certified by achalasia related to Triple A syndrome.CASE SUMMARY Triple A syndrome is a rare autosomal recessive disease characterized by adrenocorticotropic hormone-resistant adrenal insufficiency,alacrima and achalasia.In the past 5 years,POEM has proved highly successful in treating primary achalasia over the long term,but its long-term performance has not been certified by achalasia related to Triple A syndrome.Eckardt scores and esophageal manometry improved significantly during the 2 years following POEM;however,grade-A reflux esophagitis recurred in 66.7%of patients in 12 mo post-procedure.CONCLUSION Based on these case studies,POEM is efficacious and safe for a treatment of achalasia associated with Triple A syndrome.

Efficacy and safety of peroral endoscopic myotomy after prior sleeve gastrectomy and gastric bypass surgery

BACKGROUND Per-oral endoscopic myotomy(POEM)is safe and effective for the treatment of achalasia.There is limited data on performance of POEM in patients with altered upper gastrointestinal anatomy,especially after bariatric surgery.Outcomes in patients with prior sleeve gastrectomy have not been reported.AIM To assess the efficacy and safety of POEM in patients with prior bariatric surgery.METHODS A prospective POEM database was reviewed from 3/2017-5/2020 to identify patients who underwent POEM after prior bariatric surgery.Efficacy was assessed by technical success(defined as the ability to successfully complete the procedure)and clinical success[decrease in Eckardt score(ES)to≤3 post procedure].Safety was evaluated by recording adverse events.RESULTS Six patients(50%male,mean age 48 years)with a history of prior bariatric surgery who underwent POEM were included.Three had prior sleeve gastrectomy(SG)and three prior Roux-en-Y gastric bypass(RYGB).Four patients had achalasia subtype II and 2 had type I.Most(4)patients had undergone previous achalasia therapy.Technical success was 100%.Clinical success was achieved in 4(67%)patients at mean follow-up of 21 mo.In one of the clinical failures,EndoFLIP evaluation demonstrated adequate treatment and candida esophagitis was noted as the likely cause of dysphagia.There were no major adverse events.CONCLUSION POEM is technically feasible after both RYGB and SG and offers an effective treatment for this rare group of patients where surgical options for achalasia are limited.

Outcomes of per oral endoscopic pyloromyotomy in gastroparesis worldwide

Per oral endoscopic pyloromyotomy(POP),also known as gastric per-oral endoscopic myotomy(GPOEM),is a novel procedure with promising potential for the treatment of gastroparesis.As more data emerge and the procedure is becoming more recognized in clinical practice,its safety and efficacy need to be carefully evaluated.Appropriate patient selection for favorable clinical success prediction after GPOEM also needs additional research.This review aims to systemically summarize the existing data on clinical outcomes of POP.Symptomatologic responses to the procedure,its adverse effects,procedural techniques,and predictive factors of clinical success are also discussed.

Submucosal tunnel endoscopy:Peroral endoscopicmyotomy and peroral endoscopic tumor resection

Peroral endoscopic myotomy(POEM) is an innovative,minimally invasive, endoscopic treatment for esophageal achalasia and other esophageal motility disorders, emerged from the natural orifice transluminal endoscopic surgery procedures, and since the first human case performed by Inoue in 2008, showed exciting results in international level, with more than 4000 cases globally up to now. POEM showed superior characteristics than the standard 100-year-old surgical or laparoscopic Heller myotomy(LHM), not only for all types of esophageal achalasia [classical(Ⅰ), vigorous(Ⅱ), spastic(Ⅲ), Chicago Classification], but also for advanced sigmoid type achalasia(S1 and S2), failed LHM, or other esophageal motility disorders(diffuse esophageal spasm, nutcracker esophagus or Jackhammer esophagus). POEM starts with a mucosal incision, followed by submucosal tunnel creation crossing the esophagogastric junction(EGJ) and myotomy. Finally the mucosal entry is closed with endoscopic clip placement. POEM permitted relatively free choice of myotomy length and localization. Although it is technically demanding procedure, POEM can be performed safely and achieves very good control of dysphagia and chest pain. Gastroesophageal reflux is the most common troublesome side effect, and is well controllable with proton pump inhibitors. Furthermore, POEM opened the era of submucosal tunnel endoscopy, with many other applications. Based on the same principles with POEM, in combination with new technological developments, such as endoscopic suturing, peroral endoscopic tumor resection(POET), is safely and effectively applied for challenging submucosal esophageal, EGJ and gastric cardia tumors(submucosal tumors), emerged from muscularis propria. POET showed up to know promising results, however, it is restricted to specialized centers. The present article reviews the recent data of POEM and POET and discussed controversial issues that need further study and future perspectives.

Endoscopic foregut surgery and interventions:The future is now.The state-of-the-art and my personal journey

In this paper, I reviewed the emerging field of endoscopic surgery and present data supporting the contention that endoscopy can now be used to treat many foregut diseases that have been traditionally treated surgically. Within each topic,the content will progress as follows: "lessons learned", "technical considerations"and "future opportunities". Lessons learned will provide a brief background and update on the most current literature. Technical considerations will include my personal experience, including tips and tricks that I have learned over the years.Finally, future opportunities will address current unmet needs and potential new areas of development. The foregut is defined as "the upper part of the embryonic alimentary canal from which the pharynx, esophagus, lung, stomach, liver,pancreas, and part of the duodenum develop". Foregut surgery is well established in treating conditions such as gastroesophageal reflux disease(GERD), achalasia, esophageal diverticula, Barrett's esophagus(BE) and esophageal cancer, stomach cancer, gastric-outlet obstruction, and obesity. Over the past decade, remarkable progress in interventional endoscopy has culminated in the conceptualization and practice of endoscopic foregut surgery for various clinical conditions summarized in this paper. Regarding GERD, there are now several technologies available to effectively treat it and potentially eliminate symptoms, and the need for long-term treatment with proton pump inhibitors.For the first time, fundoplication can be performed without the need for open or laparoscopic surgery. Long-term data going out 5-10 years are now emerging showing extended durability. In respect to achalasia, per-oral endoscopic myotomy(POEM) which was developed in Japan, has become an alternative to the traditional Heller's myotomy. Recent meta-analysis show that POEM may have better results than Heller, but the issue of post-POEM GERD still needs to be addressed. There is now a resurgence of endoscopic treatment of Zenker's diverticula with improved technique(Z-POEM) and equipment; thus, patients are choosing flexible endoscopic treatment as opposed to open or rigid endoscopy options. In regard to BE, endoscopic submucosal dissection(ESD)which is well established in Asia, is now becoming more mainstream in the West for the treatment of BE with high grade dysplasia, as well as early esophageal cancer. In combination with all the ablation technologies(radiofrequency ablation, cryotherapy, hybrid argon plasma coagulation), the entire spectrum of Barrett's and related dysplasia and early cancer can be managed predominantly by endoscopy.Importantly, in regard to early gastric cancer and submucosal tumors(SMTs) of the stomach, ESD and full thickness resection(FTR) can excise these lesions enbloc and endoscopic suturing is now used to close large defects and perforations.For treatment of patients with malignant gastric outlet obstruction(GOO),endoscopic gastro-jejunostomy is now showing better results than enteral stenting. G-POEM is also emerging as a treatment option for patients with gastroparesis. Obesity has become an epidemic in many western countries and is becoming also prevalent in Asia. Endoscopic sleeve gastroplasty(ESG) is now becoming an established treatment option, especially for obese patients with body mass index between 30 and 35. Data show an average weight loss of 16 kg after ESG with long-term data confirming sustainability. Finally, in respect to endo-hepatology, there are many new endoscopic interventions that have been developed for patients with liver disease. Endoscopic ultrasound(EUS)-guided liver biopsy and EUS-guided portal pressure measurement are exciting new frontiers for the endo-hepatologists.

Consensus on the digestive endoscopic tunnel technique

With the digestive endoscopic tunnel technique(DETT), many diseases that previously would have been treated by surgery are now endoscopically curable by establishing a submucosal tunnel between the mucosa and muscularis propria(MP). Through the tunnel, endoscopic diagnosis or treatment is performed for lesions in the mucosa, in the MP, and even outside the gastrointestinal(GI) tract.At present, the tunnel technique application range covers the following:(1)Treatment of lesions originating from the mucosal layer, e.g., endoscopic submucosal tunnel dissection for oesophageal large or circular early-stage cancer or precancerosis;(2) treatment of lesions from the MP layer, per-oral endoscopic myotomy, submucosal tunnelling endoscopic resection, etc.; and(3) diagnosis and treatment of lesions outside the GI tract, such as resection of lymph nodes and benign tumour excision in the mediastinum or abdominal cavity. With the increasing number of DETTs performed worldwide, endoscopic tunnel therapeutics, which is based on DETT, has been gradually developed and optimized. However, there is not yet an expert consensus on DETT to regulate its indications, contraindications, surgical procedure, and postoperative treatment.The International DETT Alliance signed up this consensus to standardize the procedures of DETT. In this consensus, we describe the definition, mechanism,and significance of DETT, prevention of infection and concepts of DETTassociated complications, methods to establish a submucosal tunnel, and application of DETT for lesions in the mucosa, in the MP and outside the GI tract(indications and contraindications, procedures, pre-and postoperative treatments, effectiveness, complications and treatments, and a comparison between DETT and other operations).

Endoscopic treatment of esophageal achalasia

Achalasia is a motility disorder of the esophagus characterized by dysphagia, regurgitation of undigested food, chest pain, weight loss and respiratory symptoms. The most common form of achalasia is the idiopathic one. Diagnosis largely relies upon endoscopy, barium swallow study, and high resolution esophageal manometry(HRM). Barium swallow and manometry after treatment are also good predictors of success of treatment as it is the residue symptomatology. Short term improvement in the symptomatology of achalasia can be achieved with medical therapy with calcium channel blockers or endoscopic botulin toxin injection. Even though few patients can be cured with only one treatment and repeat procedure might be needed, long term relief from dysphagia can be obtained in about 90% of cases with either surgical interventions such as laparoscopic Heller myotomy or with endoscopic techniques such pneumatic dilatation or, more recently, with per-oral endoscopic myotomy. Age, sex, and manometric type by HRM are also predictors of responsiveness to treatment. Older patients, females and type Ⅱ achalasia are better after treatment compared to younger patients, males and type Ⅲ achalasia. Self-expandable metallic stents are an alternative in patients non responding to conventional therapies.

Techniques and efficacy of flexible endoscopic therapy of Zenker's diverticulum

Zenker's diverticulum(ZD) is an abnormal hypopharyngeal pouch often presenting with dysphagia. Treatment is often sought with invasive surgical management of the diverticulum being the only mode of definitive therapy.Primarily done by an open transcervical approach in the past, nowadays treatment is usually provided by otolaryngologists using a less invasive trans-oral technique with a rigid endoscope. When first described, this method grew into acceptance quickly due to its similar efficacy and vastly improved safety profile compared to the open transcervical approach. However, the main limitation with this approach is that it may not be suitable for all patients. Nonetheless, progress in the field of natural orifice endoscopic surgery over the last 10-20 years has led to the increase in utilization of the flexible endoscope in the treatment of ZD. Primarily performed by interventional gastroenterologists, this approach overcomes the prior limitation of its surgical counterpart and allows adequate visualization of the diverticulum independent of the patient's body habitus. Additionally, it may be performed without the use of general anesthesia and in an outpatient setting, thus further increasing the utility of this modality, especially in elderly patients with other comorbidities. Today, results in more than 600 patients have been described in various published case series using different techniques and devices demonstrating a high percentage of clinical symptom resolution with low rates of adverse events. In this article, we present our experience with flexible endoscopic therapy of Zenker's diverticulum and highlight the endoscopic technique, outcomes and adverse events related to this minimally invasive modality.

Recent advancement of therapeutic endoscopy in the esophageal benign diseases

Over the past 30 years, the field of endoscopy has witnessed several advances. With the advent of endoscopic mucosal resection, removal of large mucosal lesions have become possible. Thereafter, endoscopic submucosal resection was refined, permitting en bloc removal of large superficial neoplasms. Such techniques have facilitated the development of antireflux mucosectomy, a promising novel treatment for gastroesophageal reflux. The introduction and use of over the scope clips has allowed for endoscopic closure of defects in the gastrointestinal tract, which were traditionally treated with surgical intervention. With the development of per-oral endoscopic myotomy(POEM), the treatment of achalasia and spastic disorders of the esophagus have been revolutionized. From the submucosal tunnelling technique developed for POEM, Per oral endoscopic tumor resection of subepithelial tumors was made possible. Simultaneously, advances in biotechnology have expanded esophageal stenting capabilities with the introduction of fully covered metal and plastic stents, as well as biodegradable stents. Once deemed a primarily diagnostic tool, endoscopy has quickly transcended to a minimally invasive intervention and therapeutic tool. These techniques are reviewed with regards to their application to benign disease of the esophagus.

Microvasculature of the esophagus and gastroesophageal junction: Lesson learned from submucosal endoscopy

Advanced therapeutic endoscopy,in particular endoscopic mucosal resection,endoscopic submucosal dissection,per-oral endoscopic myotomy,submucosal endoscopic tumor resection opened a new era where direct esophageal visualization is possible.Combining these information with advanced diagnostic endoscopy,the esophagus is organized,from the luminal side to outside,into five layers(epithelium,lamina propria with lamina muscularis mucosa,submucosa,muscle layer,adventitia).A specific vascular system belonging to each layer is thus visible: Mucosa with the intra papillary capillary loop in the epithelium and the sub-epithelial capillary network in the lamina propria and,at the lower esophageal sphincter(LES) level with the palisade vessels; submucosa with the drainage vessels and the spindle veins at LES level; muscle layer with the perforating vessels; periesophageal veins in adventitia.These structures are particularly important to define endoscopic landmark for the gastro-esophageal junction,helpful in performing submucosal therapeutic endoscopy.

Recent advances in third space or intramural endoscopy

Third space endoscopy or intramural endoscopy is based on the principle that the deeper layers of the gastrointestinal tract can be accessed by tunneling in the submucosal space and maintaining the integrity of the overlying mucosa.The era of third space endoscopy started with peroral endoscopic myotomy(POEM)for treatment of achalasia and has expanded to treat various other gastrointestinal disorders.The technique is also currently used for treatment of refractory gastroparesis,Zenker’s diverticulum(ZD),resection of subepithelial tumors and early cancers of the gastrointestinal tract and Hirschsprung’s disease(HD).These procedures are rapidly emerging as minimally invasive alternatives to conventional surgery.They are safe and effective with excellent outcomes.This review focuses on the evolution and current applications of third space endoscopy in various gastrointestinal disorders.Key points:(1)Third space or intramural endoscopy initially started with the POEM procedure for treatment of achalasia;(2)Advancements in procedural techniques have expanded its application to treat other gastrointestinal disorders such as refractory gastroparesis,ZD,HD,resection of subepithelial tumors and early gastrointestinal cancers;(3)These procedures are highly effective with excellent outcomes and low complication rates;and(4)Third space endoscopic procedures are rapidly emerging as minimally invasive alternatives to conventional surgery.