Lung cancer metastasis-induced distal esophageal segmental spasm confirmed by individualized peroral endoscopic myotomy: A case report.

Predictors of Long-Term Outcomes, Recurrent Dysphagia, and Gastroesophageal Reflux After Per-oral Endoscopic Myotomy in Esophageal Motility Disorders

Tu1154 PERORAL ENDOSCOPIC MYOTOMY FOR THE TREATMENT OF ESOPHAGEAL MOTILITY DISORDERS: BASELINE CHARACTERISTICS AND PROCEDURAL OUTCOMES IN YOUNG AND ELDERLY PATIENTS

Background and study aims Peroral endoscopic myotomy (POEM) is an evolving new treatment strategy for achalasia. Although several kinds of electrosurgical knives have been used in performing POEM, the best device has yet to be determined. The FlushKnife BT is a waterjet-emitting short needle-knife with a small ball tip (BT) that offers the potential to perform all aspects of POEM with a single device. In this study, we evaluated the safety and efficiency of the FlushKnife BT for POEM.Patients and methods A total of 54 consecutive patients with achalasia and other spastic esophageal motility disorders, such as jackhammer esophagus or distal esophageal spasm, who underwent POEM between January 2016 and August 2016, were included in this retrospective study.Results The median operation time was 73.0 minutes (range 39 – 184 minutes). All procedures were completed using only the FlushKnife BT without changing to any other electrosurgical instrument. The median number of additional submucosal injections with an injection needle was 0 (range 0 – 1). Endoscopic vessel sealing was performed a mean of 3 times (range 0 – 7). The median number of bleeding episodes requiring treatment with hemostatic forceps was 0 (range 0 – 5). There were no significant adverse events. Seven of 52 patients (13.5 %) reported symptoms of gastroesophageal reflux disease such as heartburn or acid reflux at 3 month follow-up.Conclusions The FlushKnife BT enabled POEM to be performed with very few device exchanges, either for re-injection or to control intraoperative bleeding. In this uncontrolled case series, the ability of the FlushKnife BT to perform nearly all aspects of the POEM procedure seems to make it particularly well suited to this procedure.

Surgical intervention for esophageal dysmotility

Malignant pleural effusion (MPE) is associated with poor prognosis in patients with advanced lung adenocarcinoma (LUAD), and abnormal activation of epidermal growth factor receptor (EGFR) plays a crucial role in the development of LUAD. This study aimed to investigate the correlation between EGFR mutations and the occurrence of MPE in patients with LUAD and evaluate the effect of EGFR mutations on the prognosis of patients with LUAD with MPE. A case-control study design was adopted that included patients pathologically diagnosed with LUAD. Clinical data were collected, and patients were divided into the MPE group and the non-MPE (N-MPE) group based on the presence of MPE. Propensity score matching (PSM) was used to control for confounding factors. The correlation between EGFR mutations and the occurrence of MPE in LUAD was initially examined. Additionally, various factors affecting the overall survival (OS) of patients with LUAD and MPE were evaluated. A total of 849 patients were included in the study. After 1:2 PSM, there were 180 patients in the MPE group and 360 in the N-MPE group. The EGFR mutation rate was significantly higher in the MPE group compared to the N-MPE group [62.7% vs. 50.2%; odds ratio (OR) =1.668; P=0.006]. This difference was primarily attributed to the T790M mutation (8.3% vs. 1.3%; OR =8.015; P<0.001), but no significant differences observed in other mutation sites between the groups. Further evaluation of factors affecting OS in patients with LUAD and MPE revealed that EGFR mutation was an independent protective factor for OS [hazard ratio (HR) 0.662, 95% CI: 0.456-0.962; P=0.03]. For patients with LUAD, MPE, and EGFR mutations, treatment with third-generation EGFR-tyrosine kinase inhibitors (TKIs) alone (HR 0.466, 95% CI: 0.233-0.930; P=0.03) or sequential first- and third-generation EGFR-TKIs (HR 0.385, 95% CI: 0.219-0.676; P=0.001) was associated with better median OS compared to first-generation EGFR-TKIs alone (first-generation EGFR-TKIs: 35 months, 95% CI: 28.4-41.6; third-generation EGFR-TKIs: 50 months, 95% CI: 37.3-62.7; sequential first- and third-generation EGFR-TKIs: 51 months, 95% CI: 45.6-56.4; P<0.001). This study found there to be a positive correlation between EGFR mutations, particularly the T790M mutation, and MPE in patients with LUAD. EGFR mutation was associated with improved OS in patients with LUAD and MPE. For patients with LUAD, MPE, and EGFR mutations, sequential treatment with first- and third-generation EGFR-TKIs or third-generation EGFR-TKIs alone is recommended, as these regimens provide significant benefit to OS.

Aim To compare the localization of lung adenocarcinoma with tumour size and lymphovascular invasion (LVI) presence, and to determine the frequency of metastasis findings in hilar and mediastinal lymph nodes depending on the localization of the tumour and status of lymphovascular invasion. Method This observational cross-sectional study included 261 patients with complete resection of confirmed lung adenocarcinoma. The dependence between categorical variables were performed with χ2 and Fisher's exact tests. A p<0.05 was considered as statistically significant. Result Metastases to hilar lymph nodes at lung adenocarcinoma with central localization and presented lymphovascular invasion were more frequently found than tumours with peripheral localization (p<0.001). In tumours with peripheral localization, lymphovascular invasion was less frequent; even in tumours greater than 7 cm in the largest dimension the presence of LVI was not 100%. Metastases to mediastinal lymph nodes in tumours with central localization and presented lymphovascular invasion were less frequent than in tumours with peripheral localization and presented lymphovascular invasion (p=0.002). Conclusion In invasive adenocarcinoma, lymphovascular invasion was much more common in centrally positioned than in peripherally positioned tumours. Metastases to the hilar and mediastinal lymph nodes, regardless of the findings of lymphovascular invasion, usually originated from upper lobe tumours.

Spastic esophageal motility disorders (SEMD) are a rare group of motility disorders including type III achalasia, distal esophageal spasm (DES), and Jackhammer esophagus (JHE). Limited data suggest that per-oral endoscopic myotomy (POEM) may be effective in these disorders. In this study, we aimed to evaluate the long-term outcomes of POEM in SEMD. The data of patients with SEMD who underwent POEM (January 2013 to December 2019) were analyzed, retrospectively. The following outcomes were recorded: POEM procedure details, technical and clinical success, adverse events, and gastroesophageal reflux disease (GERD). Clinical success was classified as immediate (<1 y), short-term (1 to 3 y), medium term (3 to 5 y), and long-term (>5 y). A total of 1115 POEM procedures were performed during the study period for achalasia and nonachalasia spastic motility disorders. POEM was performed for SEMD in 74 (6.6%) patients including type III in 53, DES in 11, and JHE in 10 patients. Technical success was achieved in all the patients. The median follow-up for the entire group was 47.5 months (range: 2 to 77 mo). Clinical success at short-term (1 to 3 y) and long-term follow-up (>5 y) was attained in 85.2% and 82.6% patients, respectively. There was no significant difference in the clinical success between type III achalasia and JHE/DES. Mild and moderate adverse events were recorded in 21 (28.4%) cases. GERD was detected in 23 (56.1%) patients with 24-hour pH study. Erosive esophagitis and symptomatic GERD were found in 36 (48.6%) and 16 (21.6%) patients, respectively. POEM is a safe, effective, and durable treatment modality for spastic motility disorders of the esophagus. However, GERD is found in about half of the patients mandating close monitoring after POEM.

Peroral endoscopic myotomy (POEM) has been performed since 2008 on more than 5,000 patients. It has proven to be highly effective in the treatment of achalasia and has shown promising outcomes for other esophageal motility spastic disorders. A literature review of the efficacy of POEM compared to the previous invasive treatments for different esophageal motility disorders was performed. The application in the pediatric and elderly populations and its role as a rescue therapy after other procedures are also outlined. Short-term outcomes are similar to laparoscopic Heller myotomy (LHM) and pneumatic endoscopic dilation (PD) (clinical success > 90%) for achalasia subtypes I and II. Mid-term outcomes are comparable to LHM and overcome the results obtained after PD (> 90% vs ~50%). With regard to type III achalasia, POEM efficacy is 98% compared to 80.8% for LHM and the PD success remains at 40%. With regard to spastic esophageal disorders (SED), POEM has an effectiveness of 88% and 70% for distal esophageal spasm (DES) and jackhammer esophagus (JE) respectively. A response of 95% in patients with sigmoid esophagus has been reported. POEM has been performed in pediatric and elderly populations and has obtained a higher efficacy than PD in pediatric series (100% vs 33%) without greater adverse events. Previous treatments do not seem to hinder POEM results with excellent response rates, including 97% in post LHM and 100% in a re-POEM series. Final considerations: POEM has shown excellent short and mid-term results for all subtypes of achalasia but long-term results are not yet available. The promising results in SED may make POEM the first-line treatment for SED. A high-safety profile and efficacy have been shown in elderly and pediatric populations. Previous treatments do not seem to diminish the success rate of POEM. Core tip: POEM has emerged as an efficient treatment option for all subtypes of achalasia and other scenarios (including previous treatments and elderly and pediatric populations). Short and mid-term results are comparable to LHM and are better than PD data. The clinical response rate of DES and JE may make POEM the first-line treatment for SED.

Distal esophageal spasm (DES), a relatively rare condition, is characterized by simultaneous contractions of the distal esophagus and manifested by dysphagia and chest pain. Several treatment options are recommended, such as pharmacological therapy, endoscopic interventions, and surgical myotomy. Recently, per-oral endoscopic myotomy (POEM) has been adopted as an effective and less-invasive treatment due to its excellent short-term clinical outcomes. Nevertheless, few reports describe its long-term effects. A 65-year-old woman complained of chest pain accompanied with dysphagia and weight loss for 4months. A series of examinations suggested that she was suffering from DES and then POEM was performed. During the 2.5-year follow-up, we observed an exciting long-term outcome. Interestingly, hematoxylin and eosin staining verified a large number of eosinophils in the muscularis externa, which was absent in the mucosa of the esophagus of the patient. We herein report a case of DES who underwent POEM to eliminate persistent esophageal contractions. Eckardt score, esophageal emptying test, and high-resolution manometry were assumed to monitor the efficacy of POEM. During treatment and 2.5 years after operation, esophageal muscle biopsies and/or mucosal tissues were obtained. This case has been presented to describe that POEM could be a strategy for DES with a long-term curative effect and that eosinophils in the muscle layer of the esophagus might be involved in the pathogenesis of DES. What is more, we reviewed literature to find similar cases reported in the past.

ObjectivesThe efficacy and safety of peroral endoscopic myotomy (POEM) for spastic esophageal disorders (SED), including type III achalasia, distal esophageal spasm (DES), and jackhammer esophagus (JE), remain uncertain due to its rarity. This study aimed to evaluate the clinical outcomes and optimal strategies for managing SED.MethodsA retrospective analysis was conducted on patients who underwent POEM for SED between March 2014 and December 2023. Myotomy was tailored to target spastic segments in all cases. For type III achalasia, the myotomy extended into the gastric cardia, while for DES and JE, the procedure either preserved the lower esophageal sphincter (LES) or included a gastric myotomy. Outcomes assessed included procedural details, technical and clinical success, adverse events, and the incidence of gastroesophageal reflux disease (GERD) post‐POEM. Clinical success was defined as an Eckardt score of ≤3.ResultsAmong 2938 POEM procedures, 106 (3.6%) were for SED. The cohort included 58 patients (54.8%) with type III achalasia, 24 (22.6%) with DES, and 24 (22.6%) with JE. The technical success rate was 100%, with clinical success rates of 98.1% at 2–3 months and 92.6% at 1 year. Erosive esophagitis occurred in 27.7% at 2–3 months and 16.1% at 1 year. LES‐preserving POEM for DES and JE showed comparable efficacy to POEM with gastric myotomy, with a trend toward reduced GERD incidence.ConclusionPeroral endoscopic myotomy is an effective treatment for all types of SED. LES‐preserving POEM is a viable strategy for treating DES and JE, offering comparable efficacy, while potentially minimizing GERD risk.

Noncardiac chest pain (NCCP) is recurrent angina pectoris-like pain without evidence of coronary heart disease in conventional diagnostic evaluation. In gastroenterology, managing of patients with NCCP is ambiguous to detect gastroesophageal reflux and hypercontractile esophageal motility disorders. Recently, peroral endoscopic myotomy (POEM) was established as treatment option in achalasia. However, limited data exist on the effectivity of POEM in NCCP with hypercontractile esophageal motility disorders. In this prospective study (POEM-HYPE), we evaluated 14 patients with NCCP and hypercontractile esophageal motility disorders (type III achalasia, n = 7; hypercontractile esophagus, n = 6; distal esophageal spasm, n = 1). All patients underwent standardized diagnostic work-up including esophagogastroduodenoscopy with esophageal biopsies, high-resolution esophageal manometry, and combined intraluminal impedance and pH testing before and 3 weeks after POEM. A standardized symptom questionnaire was disposed before POEM, 3 weeks after, and every 6months after the POEM. After POEM, 12 patients showed significant symptom relief (pre-Eckardt score: 7.78 ± 1.47, 3 weeks post: 1.64 ± 1.44, 6 months: 2.0 ± 1.84 and 1.86 ± 1.89 after 15.0 ± 10.0 months post-intervention). High-resolution manometry showed significant reduction in integrated relaxation pressure (pre-POEM: 24.74 ± 18.9 mm Hg, post-POEM: 13.8 ± 16.5 mm Hg) and distal contractile integral (pre-POEM: 2880 ± 3700 mmHg*s*cm, post-POEM: 1109 ± 1042 mmHg*s*cm). One lesion of the submucosal tunnel occurred as a moderate adverse event and was handled endoscopically. The long-term clinical success rate was 85.7 %. No severe gastroesophageal reflux occurred after interventions. Two patients required secondary therapy with injection of botulinum toxin in the tubular esophagus and balloon dilation. The results suggest that POEM is an effective and safe therapeutic option for patients with NCCP and hypercontractile esophageal motility disorders.

Per-oral endoscopic myotomy (POEM) is a novel endoscopic procedure, which has been performed to treat achalasia with favorable outcomes. Emerging data suggest that POEM may also have a role in the treatment of patients with spastic esophageal disorders (SEDs). SEDs include spastic or type III achalasia, distal esophageal spasm (DES), and hypercontractile (Jackhammer) esophagus. Despite the difference in pathophysiology, these disorders share many similarities, including their clinical manifestations. Patients may present with one or all of the following symptoms: dysphagia, non-cardiac chest pain, regurgitation, and refractory gastroesophageal reflux symptoms. The gold standard to diagnose these disorders is high-resolution esophageal manometry. While medical therapy fails in the majority of these patients, surgical myotomy is invasive and associated with suboptimal results due to the need for long esophageal myotomy. POEM provides an ideal therapy for SEDs, as it allows for long esophageal myotomy in addition to myotomy of the lower esophageal sphincter (LES). Emerging data suggest POEM is both effective and safe for treating patients with SEDs. Similarly, gastric POEM (G-POEM) or endoscopic pyloromyotomy is a novel procedure for the treatment of patients with gastroparesis refractory to medical therapy. Emerging data suggest promising outcomes. Prospective multicenter data on POEM for SEDs and G-POEM for gastroparesis are awaited.

P1.03-074 Combined Use of PET/CT and Clinical Features Yields a Higher Diagnostic Rate of Mediastinal Lymph Node Metastasis in Lung Adenocarcinoma

Rationale: The diagnostic sensitivity of Pleural fluid (PF) cytology in malignant pleural effusions (MPE) diagnosis is about 50% on average and varies based on cancer histology. As a result, cytology negative (C-) effusions of unknown etiology undergo multiple and progressively more invasive procedures. In previous studies, we showed that extracellular vesicles (EVs) found in PF contain microRNAs, particularly miR-141-3p, that can distinguish (C+) MPE from non-malignant pleural effusion (non-MPE) with remarkable accuracy. To establish clinical utility of this approach, the next vital step is to determine whether miR-141-3p is effective in identifying (C-) MPEs. Methods: We profiled 798 miRNA using NanoString technology in a discovery set, and selected the top differentially expressed miRNA between MPE and non-MPE, followed by subsequent validation using real-time PCT (RT-PCR) in 64 (C+) MPEs [LA- and BA-MPE] and 56 non-MPE. MicroRNA-141-3p was superior to all miRNA/miRNA combinations in differentiating MPE vs non-MPE. Following this, EVs were isolated from cell-free PF of 29 (C-) MPE samples [lung adenocarcinoma (LA)-MPE=19, breast adenocarcinoma (BA)-MPE=10] where the diagnosis was made by subsequent invasive testing. After extraction, EVs were characterized by nanoparticle tracking analysis (NTA) and negative-stain transmission electron microscopy (NS-TEM) followed by total RNA extraction. The discriminatory role of miR-141-3p between (C-) MPE and non-MPE was examined, using real-time quantitative PCR (RT-PCR). Results: EVs were isolated from 29 (C-) MPE samples and underwent NTA and were further characterized by NS-TEM (Figure-1-A-C). In cell-free PF of (C-) MPE, we identified 4.86e+10 ± 1.9e+10 (mean and SD) EVs per ml (Figure-1D), compared to 4.94e+10 ± 2e+10 EVs per ml in (C+) MPE (n=12) and 2.6e+10 ± 1e+10 EVs per ml in non-MPE (n=12) with enrichment for EVs in the 70-200 nm size range. When compared with 56 non-MPE samples, miR-141-3p expression identified (C-) MPE with an AUC of &amp;gt; 0.98 (Brier score: 0.054) among all (C-) MPE groups vs non-MPE(Figure-1E-G, 1I); however, microRNA-141-3p expression did not discriminate LA-MPE from BA-MPE (AUC:0.50) (Figure-1H, 1I). Conclusion: Our findings show that pleural fluid is an abundant source of EVs in both C+ and C- MPEs and suggest that miR-141-3p can differentiate between (C-) MPE and non-MPE with remarkable accuracy. These promising results should be confirmed within larger cohorts and MPEs of different tissue of origin.

ABSTRACTIntroduction: 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.