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.     

Historical notes: The road to peroral endoscopic myotomy

Submucosal endoscopy with saftey valve mucosal flap was developed in the animal laboratory of the Mayo Clinic Developmental Endoscopy Unit. This concept, and ultimately clinical technique, was an outgrowth of earlier efforts to improve endoscopic excision of mucosal disease by manipulating the submucosa. The ability of the mucosa to readily separate from the submucosa (delaminate) was the critical observation that was refined into a method transforming the submucosa into a working space while allowing the overlying mucosal flap to serve as a protective barrier.     

Peroral endoscopic myotomy (POEM) for oesophageal achalasia: Preliminary results in humans

Background

Peroral endoscopic myotomy has been developed to provide a less invasive treatment for oesophageal achalasia compared to surgical cardiomyotomy.

Aims

To report our initial experience on feasibility, safety and clinical efficacy of peroral endoscopic myotomy.

Methods

Eleven patients (eight women, mean age 32, range 24–58) underwent an attempt at peroral endoscopic myotomy under general anaesthesia. After submucosal injection, a mucosal entry into the oesophageal submucosa, and a tunnel extending to the oesophagogastric junction and beyond into the stomach were created (total mean length: 15 ± 1.7 cm). Myotomy of the circular oesophageal and gastric muscle bundles was then achieved under direct vision (total mean length: 10.2 ± 2.8 cm). Haemostatic clips were used to close the mucosal entry. The Eckardt Score and manometry were used to evaluate the results.

Results

Peroral endoscopic myotomy could be completed in 10 out of 11 patients (91%). Mean procedure time was 100.7 min (range 75–140 min). No major complication occurred. Clinical success was achieved in all patients at 1-month follow-up (Eckardt Score 7.1 vs. 1.1, p = 0). Lower oesophageal sphincter pressure decreased from 45.1 to 16.9 mmHg (p = 0).

Conclusions

This initial experience with peroral endoscopic myotomy shows its safety and efficacy in the treatment of achalasia. Further studies are warranted to assess the long-term efficacy and to compare peroral endoscopic myotomy with other treatment modalities.     

Submucosal tunnel endoscopy: Peroral endoscopic myotomy 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.     

内镜注水泵与注射针用于贲门失弛缓症经口内镜下肌切开术治疗的对比研究（含视频）

行黏膜下注射的效果和安全性。 方法 2013年3月至2016 年2月,中国人民解放军陆军总医院消化内科126例行POEM治疗的AC患者纳入回顾性研究,对比分析POEM治疗术中使用内镜注水泵（注水泵组,n=73）和内镜注射针（注射针组,n=73）行黏膜下注射建立隧道用时、整个手术用时以及2组并发症的发生情况。 结果 注水泵组建立10～14 cm隧道用时（6.38±0.94）min,注射针组为（13.81±1.13）min,2组间差异有统计学意义（P<0.05）。注水泵组手术用时（27.81±5.76）min,注射针组为（70.25±22.67）min,2组间差异有统计学意义（P<0.05）。注水泵组术后住院时间为（4.38±1.87）d,注射针组为（5.64±1.83）d,2组间差异有统计学意义（P<0.05）。注水泵组出血发生率[5.48%（4/73）比16.98%（9/53）]、发热发生率[12.33%（9/73）比26.42%（14/53）]均低于注射针组（P<0.05）,穿孔、胸痛发生率2组间比较差异均无统计学意义（P>0.05）。 结论 POEM治疗AC过程中使用内镜注水泵替代内镜注射针行黏膜下注射安全、有效,可以有效缩短建立黏膜下隧道用时及手术用时,同时减少出血、发热等并发症的发生。     

Miotomía endoscópica por vía oral de espesor total y parcial. Estudio de factibilidad en un modelo animal

BackgroundPeroral endoscopic myotomy has recently been developed and performed on patients with good results.AimsTo evaluate the technical feasibility of peroral endoscopic full-thickness and partial thickness myotomy in a porcine model.Material and methodsEighteen criollo pigs were randomly assigned to 2 groups: group A (partial-thickness myotomy) and group B (full-thickness myotomy). The mucosal defect proximal to the myotomy site was left open. On the seventh postoperative day the pig was euthanized and follow-up surgical exploration was performed. The duration of each procedure, postoperative progression of the animal, complications, and anatomopathologic findings were registered.ResultsThe procedure was viable in all the pigs. The mean surgery duration was 81 ± 35.3 min (group A 51.11 ± 11.12, group B 111 ± 22.61; P < .05). The main complication during myotomy was subcutaneous emphysema (16%). The histopathologic study of the group A surgical specimens reported complete circular myotomy in all cases, and complete circular and longitudinal myotomy was reported in 100% of the group B sample.ConclusionsThe endoscopic myotomy technique is feasible. Endoscopic partial-thickness myotomy was associated with shorter surgery duration and better results during the intraoperative period and the 7-day follow-up.     

Offshoots of peroral endoscopic myotomy: Submucosal tunneling endoscopic resection,pyloromyotomy, and beyond

The emergence of peroral endoscopic myotomy (POEM) marks the rising of a new branch of therapeutic endoscopy. Our group defines it as tunnel endoscopic surgery that includes several novel procedures utilizing a submucosal tunnel as an operating space. In 2010, we developed a new procedure that takes advantage of the submucosal tunneling technique popularized by POEM to achieve complete, full-thickness endoscopic resection of upper gastrointestinal submucosal tumors originating from the muscularis propria layer. Our group coined the acronym STER (submucosal tunneling endoscopic resection) for this procedure. Herein, we summarize this novel method and other offshoots of POEM.     

Same site submucosal tunneling for a repeat per oral endoscopic myotomy: A safe and feasible option

Per oral endoscopic myotomy (POEM) is a novel endoscopic procedure for achalasia treatment. Due to its novelty and high success rates, a repeat procedure is usually not warranted, making the feasibility and safety of such approach unknown. We report the first case of a successful repeat POEM done at the same site of a previously uncompleted POEM. An 84-year-old female with type 2 achalasia presented for a POEM procedure. The procedure was aborted at the end of tunneling and before myotomy due to hypotension, which later resolved spontaneously. POEM was re-attempted at the same site of the original tunnel 1 year afterward, and surprisingly we didn’t encounter any submucosal fibrosis. The procedure felt similar to a native POEM and a myotomy was performed uneventfully. Our case is the first to suggest that submucosal tunneling during a repeat POEM can be done at the same site. Hypotension during POEM is a rare complication that should be recognized as a potential result of tension capnothorax, it can however, be managed with close supportive care.     

经食管后壁内镜肌切开术治疗贲门失弛缓症的初步评价

目的 探讨经食管后壁内镜肌切开术(POEM)治疗贲门失弛缓症的有效性及安全性.方法 选择诊断明确的贲门失弛缓症患者,经食管后壁行POEM,观察手术前后患者的吞咽困难的积分、食管下括约肌静息压变化、手术并发症等.结果 28例贲门失弛缓症患者入选研究,其中26例患者顺利施行经食管后壁的POEM,平均手术时间68.8 min,无一例患者发生严重危及生命的手术并发症.26例患者术后食管下括约肌静息压力较术前平均降低16.37 mm Hg(1 mmHg =0.133 kPa),术后1个月Eckardt评分均分较术前降低6.69分,仅1例患者仍有吞咽困难,Eckardt评分为4分,总有效率96.1％ (25/26).1例患者术后出现反流症状.2例患者因贲门部严重疤痕形成而未能完成POEM手术.结论 经食管后壁POEM能即时有效地改善贲门失弛缓症患者吞咽困难的临床症状,有效降低食管下括约肌静息压力,短期疗效满意,其并发症尤其是气胸发生率较低,安全性较高.     

Per-oral endoscopic myotomy: Major advance in achalasia treatment and in endoscopic surgery

Per-oral endoscopic myotomy (POEM) represents a natural orifice endoscopic surgery (NOTES) approach to laparoscopy Heller myotomy (LHM). POEM is arguably the most successful clinical application of NOTES. The growth of POEM from a single center in 2008 to approximately 60 centers worldwide in 2014 with several thousand procedures having been performed attests to the success of POEM. Initial efficacy, safety and acid reflux data suggest at least equivalence of POEM to LHM, the previous gold standard for achalasia therapy. Adjunctive techniques used in the West include impedance planimetry for real-time intraprocedural luminal assessment and endoscopic suturing for challenging mucosal defect closures during POEM. The impact of POEM extends beyond the realm of esophageal motility disorders as it is rapidly popularizing endoscopic submucosal dissection in the West and spawning offshoots that use the submucosal tunnel technique for a host of new indications ranging from resection of tumors to pyloromyotomy for gastroparesis.     

内镜对穿隧道肿瘤切除术治疗贲门巨大黏膜下肿瘤的临床分析

目的　探讨内镜对穿隧道肿瘤切除术（submucosal tunnel docking endoscopic resection,SDER）治疗贲门巨大黏膜下肿瘤的安全性、有效性。方法　回顾性收集2021年1月—2022年1月在复旦大学附属中山医院和徐汇区中心医院内镜中心行SDER治疗的贲门巨大黏膜下肿瘤患者资料,分析手术记录、术后病理、并发症、住院情况及随访情况。结果　本研究共纳入6例患者,病变平均长径为4.0 cm,均位于贲门。所有患者成功完成SDER治疗,手术时间为23~42 min。术后病理提示4例为平滑肌瘤,2例为胃肠间质瘤,所有病变完全切除。术后住院时间为3~5 d。6例患者术后均未出现严重并发症。所有患者术后3个月和6个月复查胃镜恢复良好。结论　初步认为,利用SDER治疗贲门巨大黏膜下肿瘤是安全、有效的。     

经口内镜下肌切除术治疗贲门失弛缓症的临床疗效观察

目的 观察经口内镜下肌切除术(POEM)治疗贲门失弛缓症的临床疗效和安全性.方法 对2010年11月至2011年11月7例确诊为贲门失弛缓症的患者行POEM手术.记录术前吞咽困难评分、术后并发症及近期远期疗效.结果 7例患者POEM手术均成功.手术时间46～113 min,平均(73±20) min.术后除2例出现皮下气肿、纵隔气肿,经内科治疗后痊愈,余均未出现相关并发症.术后随访1～12个月,7例患者吞咽困难均得到明显改善.结论 POEM手术可以迅速解除贲门失弛缓症患者吞咽困难,且具有一定的安全性.     

Peroral endoscopic myotomy as salvation technique post‐Heller: International experience

Background

Treatment for achalasia has traditionally been Heller myotomy (HM). Despite its excellent efficacy rate, a number of patients remain symptomatic post‐procedure. Limited data exist as to the best management for recurrence of symptoms post‐HM. We present an international, multicenter experience evaluating the efficacy and safety of post‐HM peroral endoscopic myotomy (POEM).

Methods

Patients who underwent POEM post‐HM from 13 centers from January 2012 to January 2017 were included as part of a prospective registry. Technical success was defined as successful completion of the myotomy. Clinical success was defined as an Eckardt score of ≤3 on 12‐month follow up. Adverse events (AE) including anesthesia‐related, operative, and postoperative complications were recorded.

Results

Fifty‐one patients were included in the study (mean age 54.2, 47% male). Technical success was achieved in 100% of patients. Clinical success on long‐term follow up was achieved in 48 patients (94%), with a mean change in Eckardt score of 6.25. Seven patients (13%) had AE: six experienced periprocedural mucosal defect treated endoscopically and two patients developed mediastinitis treated conservatively.

Conclusion

For patients with persistent symptoms after HM, POEM is a safe salvation technique with good short‐term efficacy. As a result of the challenge associated with repeat HM, POEM might become the preferred technique in this patient population. Further studies with longer follow up are needed.     

Perspective on Peroral Endoscopic Myotomy for Achalasia: Zhongshan Experience

Worldwide, peroral endoscopic myotomy (POEM) has achieved remarkable initial outcomes in the treatment of achalasia. In China, POEM has developed very quickly since the first case was performed in our center in August 2010. With experience, we have successfully performed POEM for special cases (such as pediatric patients, patients with sigmoid-type esophagus, and patients with recurrent symptoms after previous surgery) and have altered our technique to achieve long-term symptom remission and simplify the POEM procedure. These changes include posterior wall incision, full-thickness myotomy, a “push-and-pull” technique for myotomy, and water-jet assisted POEM. In this article, our experiences in POEM are summarized, including changes in technique, applications of the procedure, and the management of possible complications.