Third space endoscopy (TSE) offers diverse treatment options for a variety of conditions of the gastrointestinal tract and motility disorders. Accuracy and precise dissection have helped treat complex conventional surgeries with TSE. Despite over a decade of its presence, difficult situations are routinely encountered.

The first challenging situation is decision-making (before the procedure), the second is tackling procedure-induced pulmonary / insufflation-related adverse events and intra-operative complications (during the procedure), and the third is post-operative complications and morbidity (post-procedure). The performance of TSE procedures is not without risk. Patients should receive enough time to weigh their options, considering that attitudes toward risk impact decision-making. Continuous basic patient monitoring and the micro-movements of endoscopic and electrosurgical equipment is crucial to avoid accidental injury. Anaesthetists should be mindful of anticipated complications and closely monitor, diagnose, and treat them. Demanding situations need careful consideration, problem-solving, or persistence to overcome challenges. This brief review provides inputs on preventing and tackling difficult situations in TSE.

For recurrent achalasia after initial peroral endoscopic myotomy (POEM) failure, repeat POEM (Re-POEM) has been reported as a treatment option. However, severe esophageal interlayer adhesions caused by previous procedures impede the successful establishment of a submucosal tunnel and lead to aborted Re-POEM procedures. Our team previously described POEM with simultaneous submucosal and muscle dissection (POEM-SSMD) as a feasible solution for achalasia with severe interlayer adhesions.

To investigate the effectiveness and safety of Re-POEM with simultaneous submucosal and muscle dissection (Re-POEM-SSMD).

A total of 1049 patients with achalasia who underwent successful endoscopic myotomy at the Digestive Endoscopic Center of Chinese PLA General Hospital from December 2014 to May 2022 were reviewed. Patients with recurrent achalasia who experienced initial POEM clinical failure were retrospectively included in this study. The primary endpoint was retreatment clinical success, defined as an Eckardt score ≤ 3 during the postretreatment follow-up and no need for additional treatment. Procedure-related adverse events, changes in manometric lower esophageal sphincter (LES) pressure and reflux complications, as well as procedure-related parameters, were recorded.

Sixteen patients underwent Re-POEM (9 patients) or Re-POEM-SSMD (7 patients) successfully at a median of 45.5 mo (range, 4-95 mo) after initial POEM. During a median follow-up period of 31 mo (range, 7-96 mo), clinical success (Eckardt score ≤ 3) was achieved in 8 (88.9%) and 6 (85.7%) patients after Re-POEM and Re-POEM-SSMD, respectively (P = 0.849). The median Eckardt score dropped from 4 (range, 3-8) at preretreatment to 1 (range, 0-5) at postretreatment in the Re-POEM group (P = 0.025) and from 5 (range, 2-8) to 2 (range, 0-4) in the Re-POEM-SSMD group (P < 0.001). The mean manometric LES pressure decreased from 23.78 ± 9.04 mmHg to 11.45 ± 5.37 mmHg after Re-POEM (P < 0.001) and from 26.80 ± 7.48 mmHg to 11.05 ± 4.38 mmHg after Re-POEM-SSMD (P < 0.001). No serious adverse events were recorded in both groups.

In conclusion, Re-POEM-SSMD appears to be a safe and effective salvage therapy for recurrent achalasia with severe interlayer adhesions.

Peroral endoscopic myotomy is associated with a low risk of adverse events. Mucosal injury is the most common intraprocedural adverse event of peroral endoscopic myotomy. Severe mucosal injury may cause serious consequences, such as esophageal leak and mediastinitis, which affect the outcome of the procedure and prolong hospital stay. The aim of the present study was to determine the characteristics, predictors, and management approaches for unintended mucosal injury during peroral endoscopic myotomy.

A total of 211 patients who underwent peroral endoscopic myotomy between November 2014 and June 2019 were enrolled in this study. Mucosal injury was defined according to a previous study and maintained in the endoscopy database. Patient-related and procedure-related factors were compared between patients with and without mucosal injury. Multivariate analysis was performed after adjusting for confounding factors.

A total of 206 patients were eligible for study enrollment. Of these, 44 experienced mucosal injury, with an overall frequency of 21.4% (44/206). On multivariable analysis, mucosal injury was associated with submucosal fibrosis (odds ratio, 8.33; P = .024), intraprocedural bleeding (OR, 14.29; P < .001), endoscopic diameter of 9.9 mm (OR, 4.389; P = .006), and procedure duration over 60 minutes (OR, 1.016; P = .034).

Mucosal injury is a significant event encountered during peroral endoscopic myotomy, affecting its short- and long-term outcomes. Intra-procedural bleeding, endoscopic submucosal fibrosis, and use of an endoscope with a large outer diameter have been found to be significant predictors of mucosal injury. Endoscopists should pay more attention to risk factors associated with mucosal injury to avoid adverse events.

Although esophageal smooth muscle fibrosis of achalasia (AC) patients has been described, the role and mechanism remain unclear. The aim of this study was to evaluate the fibrosis in the distal esophageal muscle in patients with AC and explore its relationship with prognosis of per-oral endoscopic myotomy (POEM).

Lower esophageal sphincter (LES) muscle from forty patients undergoing POEM for AC were obtained at the time of surgery. Control specimens consisted of similar muscle taken from distal esophagectomy for gastric tumors. The muscle fibrosis were assessed by Masson staining and confirmed by immunohistochemistry for collagen I and III. The total number of eosinophil within the myenteric propria were counted. In addition, clinical data were obtained through electronic medical records. Statistical comparison between groups were made.

A significantly higher proportion of fibrosis in AC as compared with controls (P = 0.000). Eosinophil count, TGF-β1, collagen I, and III were higher than those of control (P = 0.000, P = 0.001, P = 0.011, and P = 0.002, respectively). TGF-β1, collagen I, and III were positively correlated with eosinophil count (all P < 0.05). Furthermore, the proportion of severe LES fibrosis in patients who failed to respond to POEM two years after operation was higher than that in responders (P = 0.028). And, Eckardt score two years after POEM was also positively correlated with degree of fibrosis-related cytokines (all P < 0.05).

Smooth muscle fibrosis was prominent in lower part of esophagus of AC and positively correlated with severity of symptoms two years after POEM. The fibrosis might be relevant to eosinophil infiltration and TGF-β1. Further studies are required to more clearly delineate the mechanism of muscle fibrosis and its correlation with prognosis of therapy for this idiopathic disease.

Achalasia, a rare primary esophageal motility disorder, is often misdiagnosed as refractory gastroesophageal reflux disease (GERD). This study is aimed to identify the clinical and histopathologic features that may help to differentiate these two entities. Patients with untreated achalasia and those with refractory reflux symptoms despite ≥8 weeks of proton-pump inhibitor treatment were enrolled prospectively. All patients underwent validated symptom questionnaires, esophagogastroduodenoscopy with biopsy, and high-resolution impedance manometry (HRIM). Histopathology of esophageal mucosa was compared based on four pre-determined histological criteria: basal cell hyperplasia or papillae elongation, eosinophilic infiltration, petechiae formation, and hypertrophy of the muscularis mucosae (MM). Compared with the GERD patients, patients with achalasia had similar reflux symptoms, but higher Eckardt scores, fewer erosive esophagitis and hiatal hernia, more esophageal food retention on endoscopy, and higher prevalence of hypertrophy of the MM and petechiae formation on histopathology. Multivariate logistic regression based on Eckardt score ≥4, normal esophagogastric junction morphology or esophageal food retention, and coexistence of petechiae formation and hypertrophy of the MM, established the best prediction model for achalasia. Therefore, combination of routinely accessible variables, including Eckardt score, endoscopic features, and histopathology obtained via esophageal mucosal biopsy, may provide an earlier identification of achalasia.

Background and study aims  Submucosal fibrosis (SMF) is one of the major reasons for technical failure during per-oral endoscopic myotomy (POEM). In this study, we aimed to evaluate the impact of double tunnel technique (DT-POEM) on the technical success of POEM in cases with severe SMF. Patients and methods  Data from patients with achalasia in whom SMF was encountered during POEM from Jan 2013 to Jan 2020 at our center were retrospectively evaluated. The technical success and adverse events (AEs) were analyzed and compared between cases with SMF who underwent POEM via single tunnel versus DT-POEM technique. Results  A total of 1,150 patients underwent POEM during the study period. There were 14 technical failures (1.2 %). SMF and severe SMF was found in 104 (9 %) and 21 (1.8 %) patients, respectively. The majority of patients (17, 80.9 %) with severe SMF had type I achalasia. Overall, technical failures occurred in 14 cases (1.2 %) and severe SMF resulted in the majority of the technical failures (10, 71.4 %). DT-POEM was utilized in 11 cases (52.4 %) with severe SMF. The median procedure time with DT-POEM was 150 minutes (85-210). There were no major AEs and DT-POEM was technically successful in all the patients. The technical success of POEM in cases with SMF improved after the adoption of the double tunnel technique (98.4 % vs 68.3 %, P  = 0.0001). Conclusions  Severe SMF is the most common reason for technical failure during POEM. DT-POEM improves the technical success rates of POEM in patients with severe SMF.

Peroral endoscopic myotomy (POEM) has been shown to be effective for achalasia patients. Our study aimed to analyze the clinical outcomes of POEM for challenging patients.

We retrospectively enrolled 278 challenging achalasia patients who underwent POEM from January 2011 to July 2019. The outcomes of POEM such as procedure time, adverse events, and risk factors of adverse events were analyzed.

Of the 278 patients (134 males and 144 females) with a mean age of 47.0 years, 103, 223, 93, and 98 patients had prior treatment and were Ling classification IIc/III, submucosal fibrosis (SMF) classification 2/3, and esophageal mucosa in achalasia (EMIA) classification c/d/e/f, respectively. The mean procedure time was 45.9 min (range, 15-158 min). The mean length of the tunnel and myotomy were 10.1 cm (range, 7-17 cm) and 6.6 cm (range, 5-13 cm), respectively. The major adverse event rate was 14.1%, while the minor adverse event rate was 4.7%. SMF classification 2/3 was an independent risk factor for incomplete tunneling, adverse events, and procedure time ≥ 90 min. The mean follow-up time was 37.2 months (range 1-99 months). The mean Eckardt score and esophageal sphincter pressure were both significantly declined postoperatively. The clinical success rate was 95.6%.

POEM is safe and effective for challenging achalasia patients. SMF classification grade 2/3 was shown to be an independent risk factor for incomplete tunneling, adverse events, and procedure time ≥ 90 min. For these patients, POEM should be performed by experienced endoscopists, some cases are better served with traditional surgery, such as minimally invasive Heller with Dor fundoplication.

Introduction: Peroral endoscopic myotomy (POEM) has been established as an alternative endoscopic method for the treatment of achalasia, and several studies have confirmed its relatively long-term efficacy. Although most of the POEM procedures can be smoothly completed, technical difficulties do arise during the treatment of some patients, which may lead to prolonged procedure duration, increased procedure-related complications, or even aborted POEM.Area covered: In the present review, we provide a comprehensive review of difficult POEM, focusing on its definition, risk factors, and intraoperative management strategies. The present review is expected to provide tips for not so experienced operators who perform POEM.Expert commentary: Submucosal fibrosis and sigmoid-type esophagus are associated with difficult POEM. Sometimes, the following may also be associated with difficult POEM: previous endoscopic or surgical treatments, spastic esophageal disorders (type III achalasia, distal esophageal spasm, and hypercontractile esophagus), achalasia with diverticulum or situs inversus. For operators who begin to perform POEM, I suggest an exclusion of patients with severe submucosal fibrosis or sigmoid-type esophagus, and begin to perform POEM for these patients when they have completed at least 50 cases of 'easy POEM' and the proposed management strategies may be helpful.

The main scope of this review article is to introduce readers to the innovative field of third-space endoscopy and offer a closer look at its history, milestones, and procedure spectrum while discussing ongoing and future challenges arising from its increasing adoption worldwide.

Over the past few years, third-space endoscopy has been utilized in various diagnostic and interventional procedures performed throughout the gastrointestinal tract: obliteration of Zenker's diverticulum, myotomy for achalasia, gastroparesis or Hirschsprung's disease, biopsy or removal of subepithelial tumors, stricture management, post-per-oral endoscopic myotomy endoscopic fundoplication, and mediastino-, thoraco-, and peritoneoscopy. Third-space endoscopic interventions have revolutionized the management of esophageal motility disorders, gastroparesis, and gastrointestinal tract subepithelial tumors. Despite the high efficacy and safety of such interventions, some common (e.g., the high level of necessary endoscopic skill) and unique for each procedure (e.g., post-procedure gastroesophageal reflux or poor outcomes in patient subgroups) challenges still remain. Through a dedicated endoscopic training, a rigorous pre-procedure patient evaluation and selection, and the application of modified or new techniques, challenges can be overcome thus establishing existing procedures and paving the way for additional breakthroughs in the field of third-space endoscopy.

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 DETT-associated 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).