Endoscopic submucosal dissection versus endoscopic mucosal resection for the treatment of rectal lesions involving the dentate line.

BACKGROUND: The ideal treatment of epithelial neoplastic rectal lesions involving the dentate line is a controversial issue. Piecemeal endoscopic mucosal resection (EMR) is the most commonly used resection technique, but it is associated with high recurrence rates. Endoscopic submucosal dissection (ESD) has been shown to be safe and effective for the treatment of rectal lesions, but evidence is lacking concerning its application close to the dentate line. The aim of our study is to compare ESD and EMR for the treatment of epithelial rectal lesions involving the dentate line. METHODS: We identified all cases of endoscopic resections of rectal lesions involving the dentate line performed in two German high-volume centers between 2010 and 2022. Periinterventional and follow-up data were collected and retrospectively analyzed. RESULTS: We identified 68 ESDs and 62 EMRs meeting our inclusion criteria. ESD showed a significant advantage in en bloc resection rates (89.7% vs. 9.7%; P = 0.001) and complete resection rates (72.1% vs. 9.7%; P = 0.001). The overall curative resection rate was similar between both groups (ESD: 92.6%, EMR: 83.9%; P = 0.324), whereas in the subgroup of low-risk adenocarcinomas ESD was curative in 100% of the cases vs. 14% in the EMR group (P = 0.002). There was one local recurrence after ESD (1,5%) vs. 16 (25.8%) after EMR (P < 0.0001), and the EMR patients required an average of three further interventions. CONCLUSION: ESD is superior to EMR for the treatment of epithelial rectal lesions involving the dentate line and should be considered the treatment of choice.

Endoscopic Resection of Malignancies in the Upper GI Tract: A Clinical Algorithm.

Background: Malignancies in the upper gastrointestinal tract are amenable to endoscopic resection at an early stage. Achieving a curative resection is the most stringent quality criterion, but post-resection risk assessment and aftercare are also part of a comprehensive quality program. Summary: Various factors influence the achievement of curative resection. These include endoscopic assessment prior to resection using chromoendoscopy and HD technology. If resectability is possible, it is particularly important to delineate the lateral resection margins as precisely as possible before resection. Furthermore, the correct choice of resection technique depending on the lesion must be taken into account. Endoscopic submucosal dissection is the standard for esophageal squamous cell carcinoma and gastric carcinoma. In Western countries, it is becoming increasingly popular to treat Barrett's neoplasia over 2 cm in size and/or with suspected submucosal infiltration with en bloc resection instead of piece meal resection. After resection, risk assessment based on the histopathological resection determines the patient's individual risk of lymph node metastases, particularly in the case of high-risk lesions. This is categorized according to the current literature. Key Messages: This review presents clinical algorithms for endoscopic resection of esophageal SCC, Barrett's neoplasia, and gastric neoplasia. The algorithms include the pre-resection assessment of the lesion and the resection margins, the adequate resection technique for the respective lesion, as well as the post-resection risk assessment with an evidence-based recommendation for follow-up therapy and surveillance.

Endoscopic Submucosal Dissection for Early Esophageal Adenocarcinoma: Low Rates of Metastases in Mucosal Cancers with Poor Differentiation.

BACKGROUND AND AIMS: Endoscopic resection (ER) is accepted as standard treatment for intramucosal esophageal adenocarcinoma (EAC) with well or moderate differentiation. Poor differentiation (PD) is judged as a risk factor for lymph node metastasis (LNM) and surgery is recommended. However, the evidence for this recommendation is weak. Study aim was to analyze the clinical course of patients after ER of EAC with PD. PATIENTS AND METHODS: Patients undergoing endoscopic submucosal dissection for EAC were included from 16 German centers. Inclusion criteria were PD in the resection specimen, R0 resection and endoscopic follow-up. Primary outcome was the metastasis rate during follow-up. Analysis was performed retrospectively in a prospectively collected database. RESULTS: 25 patients with PD as single risk factor (group A) and 15 patients with PD and additional risk factors (submucosal invasion and/or lymphovascular invasion) were included. The metastasis rate was was 1/25 (4.0%; 95%CI 0.4-17.2) in group A and 3/15 (20.0%; 95%CI 6.0-44.4%) in group B, respectively (p=0.293). The rate of EAC-associated deaths was 1/25 (4%; 95%CI 0.4-17.2%) versus 3/15 (20%; 95%CI 6.0-44.4%) in group B (p=0.293) while the overall death rate was 7/25 (28.0%; 95%CI 13.5-47.3%) versus 3/15 (20%; 95%CI 6.0-44.4%) (p=0.715). Median follow-up was 30 months (IQR 15-53). CONCLUSIONS: During long-term follow-up the risk of metastasis is low after ER of mucosal EAC with PD as single risk factor. A conservative approach seems justified in this small patient group. However, the treatment strategy has to be determined on an individualized basis until further prospective data are available.

[Therapy of esophageal motility disorders]. / Therapieoptionen von primären Motilitätsstörungen des Ösophagus.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2020 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

pTEVAR of an aorto-esophageal fistula in esophageal cancer: Case report and review of the literature.

An aorto-esophageal fistula (AEF) is a rare and life-threatening situation, associated with aneurysms, foreign bodies, infiltrating tumors, and radiotherapy. The ideal management is unclear. Open surgery of AEF has a high mortality and morbidity. Thoracic endovascular aortic repair (TEVAR) of an AEF is an effective and safe emergency treatment for these patients. We describe a case of AEF due to esophageal cancer successfully treated the first time by total percutaneous TEVAR (pTEVAR). A 70-year-old male patient presented with massive hematemesis at the emergency department. The patient had a known history of esophageal cancer previously treated by radiochemotherapy which was completed 3 days before. Emergency upper gastrointestinal endoscopy failed to stop the bleeding. Subsequent contrast-enhanced computed tomography revealed an aorto-esophageal fistula and emergency pTEVAR was performed. The bleeding stopped directly after stent graft placement and the patient was discharged after 10 days later. He died 3 months after pTEVAR from cancer progression. pTEVAR is an effective and safe treatment option for AEF. It can be applied as a first-line treatment and offers the potential to improve survival in the emergency setting.

[Diagnosis of esophageal motility disorders - Significance of the new Chicago classification v4.0]. / Diagnostik von Motilitätsstörungen des Ösophagus ­ Bedeutung der neuen Chicago-Klassifikation v4.0.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2021 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

Characteristics of familial pancreatic cancer families with additional colorectal carcinoma.

Familial pancreatic cancer (FPC) is a rare hereditary tumor entity with broad phenotypic heterogeneity, including colorectal carcinoma (CRC) in some families. The underlying factors for this co-occurrence are still not well evaluated. FPC families in the National Case Collection of Familial Pancreatic Cancer with an additional occurrence of CRC were analyzed regarding the phenotype, genotype and recommendation for a clinical screening program. The total cohort of 272 FPC families included 30 (11%) families with at least one CRC case. The proportion of affected family members with PDAC was 16.1% (73/451) compared to 9.3% of family members with CRC (42/451, p < 0.01). Females were affected with PDAC in 49% (36/73) and CRC in 38% (16/42). The median age of PDAC was 63 compared to 66 years in CRC, whereas 8 (26.6%) of families had an early onset of PDAC and 2 (6.7%) of CRC. Seventeen families had 2 or more affected generations with PDAC and 6 families with CRC. Eleven (9.6%) of affected patients had both PDAC and CRC. Potentially causative germline mutations (2 ATM, 1 CDKN2a, 1 MLH1, 1 PALB2) were detected in 5 of 18 (27.7%) analyzed cases. These findings provide a step forward to include the phenotypic and genotypic characteristics of FPC-CRC families for the genetic counseling and management of these families. Nevertheless, results need to be verified in a larger patient cohort beforehand.

[Therapy of esophageal motility disorders]. / Therapieoptionen von primären Motilitätsstörungen des Ösophagus.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2020 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

Digital single-operator pancreatoscopy for the treatment of symptomatic pancreatic duct stones: a prospective multicenter cohort trial.

BACKGROUND: Digital single-operator pancreatoscopy (DSOP)-guided lithotripsy is a novel treatment modality for pancreatic endotherapy, with demonstrated technical success in retrospective series of between 88 % and 100 %. The aim of this prospective multicenter trial was to systematically evaluate DSOP in patients with chronic pancreatitis and symptomatic pancreatic duct stones. METHODS: Patients with symptomatic chronic pancreatitis and three or fewer stones ≥ 5mm in the main pancreatic duct (MPD) of the pancreatic head or body were included. The primary end point was complete stone clearance (CSC) in three or fewer treatment sessions with DSOP. Current guidelines recommend extracorporeal shock wave lithotripsy (ESWL) for MPD stones > 5 mm. A performance goal was developed to show that the CSC rate of MPD stones using DSOP was above what has been previously reported for ESWL. Secondary end points were pain relief measured with the Izbicki pain score (IPS), number of interventions, and serious adverse events (SAEs). RESULTS: 40 chronic pancreatitis patients were included. CSC was achieved in 90 % of patients (36/40) on intention-to-treat analysis, after a mean (SD) of 1.36 (0.64) interventions (53 procedures in total). The mean (SD) baseline IPS decreased from 55.3 (46.2) to 10.9 (18.3). Overall pain relief was achieved in 82.4 % (28/34) after 6 months of follow-up, with complete pain relief in 61.8 % (21/34) and partial pain relief in 20.6 % (7/34). SAEs occurred in 12.5 % of patients (5/40), with all treated conservatively. CONCLUSION: DSOP-guided endotherapy is effective and safe for the treatment of symptomatic MPD stones in highly selected patients with chronic pancreatitis. It significantly reduces pain and could be considered as an alternative to standard ERCP techniques for MPD stone treatment in these patients.

[Diagnosis of esophageal motility disorders - Significance of the new Chicago classification v4.0]. / Diagnostik von Motilitätsstörungen des Ösophagus ­ Bedeutung der neuen Chicago-Klassifikation v4.0.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2021 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

Endoscopic Vacuum Therapy for Iatrogenic Rectal Perforation.

Serious iatrogenic bowel injuries during screening colonoscopy are rare events. If a perforation is detected during colonoscopy, endoscopic therapy can be attempted depending on the size and type as well as local endoscopic experience. We report the case of a 54-year-old female patient who was treated by endoscopic vacuum therapy (EVT) for a rectal perforation she had suffered during an outpatient screening colonoscopy. Two hours after the complication, an emergency endoscopy was performed. A perforation of the lower third of the rectum with a longitudinal diameter of 4 cm and a depth of 2.5 cm was detected. Due to the deep defect and the suspected increased risk of abscess formation after mechanical perforation closure with endoclips, we decided to perform EVT. The therapy was performed over a total period of 7 days. The patient was symptom free at all times. On the 2nd and 5th day, the endoscopic findings were re-evaluated and the inserted endosponges were changed. The sponge was adjusted to the wound conditions at each check and its length was gradually shortened. The endoscopic findings improved steadily. The EVT was completed after 7 days with the result of complete wound closure. The inflammatory parameters dropped continuously from day 1. On day 8, the patient could be discharged from inpatient treatment. No complications occurred in the post-inpatient course. This case is an example of successful EVT after iatrogenic rectal perforation. EVT should be considered for iatrogenic rectal perforation when signs of systemic inflammation are present and primary mechanical wound closure appears critical due to the depth of the defect and the presumed risk of abscess formation.

Endoscopic vacuum therapy (EVT) for acute esophageal perforation: Could it replace surgery?

Background and study aims Acute esophageal perforation is a potentially life-threating condition that demands a multidisciplinary approach. Based on recently published data indicating that EVT may be effective in managing esophageal perforation, we report our institution's experience with EVT in this clinical setting. Patients and methods We retrospectively analyzed all 10 patients with acute esophageal perforation from May 2018 to January 2021, using descriptive statistics. The primary outcome was successful closure of the perforation. Secondary outcomes included the length of treatment, number of endoscopic procedures required, and complication rate. Results All patients (site of perforation: 4 upper, 2 middle, 4 lower esophagus; etiology: 8 iatrogenic, 2 foreign body ingestion) were treated with EVT successfully. In eight cases, EVT was started immediately after the perforation, in the other two cases 1 and 2 days later. The median (interquartile range) number of endoscopic procedures was 2.5 (range, 2-3) and the median duration of treatment was 7.5 days (range, 7-11.5). The sponge was placed in eight cases intraluminally, in the other two cases initially intracavitary. No complication occurred. Conclusions EVT is highly effective for managing acute esophageal perforation within 1 to 3 weeks. Immediate start of EVT to prevent abscess formation and induce defect closure is crucial.

SEVTAR-A multicenter randomized controlled trial to investigate the impact of prophylactic endoluminal placed vacuum sponge for prevention of anastomotic leakage after low rectal resections.

Background: Low anterior resection for rectal cancer is commonly associated with a diverting stoma. In general, the stoma is closed 3 months after the initial operation. The diverting stoma reduces the rate of anastomotic leakage as well as the severeness of a potential leakage itself. Nevertheless, anastomotic leakage is still a life-threatening complication and might reduce the quality of life in the short and long term. In case of leakage, the construction can be converted into a Hartmann situation or it could be treated by endoscopic vacuum therapy or by leaving the drains. In recent years, endoscopic vacuum therapy has become the treatment of choice in many institutions. In this study, the hypothesis is to be evaluated, if a prophylactic endoscopic vacuum therapy reduces the rate of anastomotic leakage after rectal resections. Methods: A multicenter parallel group randomized controlled trial is planned in as many as possible centers in Europe. The study aims to recruit 362 analyzable patients with a resection of the rectum combined with a diverting ileostoma. The anastomosis has to be between 2 and 8 cm off the anal verge. Half of these patients receive a sponge for 5 days, and the control group is treated as usual in the participating hospitals. There will be a check for anastomotic leakage after 30 days. Primary end point is the rate of anastomotic leakages. The study will have 60% power to detect a difference of 10%, at a one-sided alpha significance level of 5%, assuming an anastomosis leakage rate of 10%-15%. Discussion: If the hypothesis proves to be true, anastomosis leakage could be reduced significantly by placing a vacuum sponge over the anastomosis for 5 days. Trial registration: The trial is registered at DRKS: DRKS00023436. It has been accredited by Onkocert of the German Society of Cancer: ST-D483. The leading Ethics Committee is the Ethics Committee of Rostock University with the registration ID A 2019-0203.

Gastric enterochromaffin-like cell changes in multiple endocrine neoplasia type 1.

BACKGROUND: Gastric enterochromaffin-like cell (ECL) tumours can occur in patients with multiple endocrine neoplasia type 1 (MEN1), especially in those affected by Zollinger Ellison syndrome (ZES). Since the prevalence of ECL lesions is not well defined yet, the present study evaluated the presence and extent of ECL lesions in MEN1 patients with and without ZES. METHODS: Multiple endocrine neoplasia type 1 patients being part of a regular screening program (2014-2018) underwent gastroduodenoscopies with biopsies of the stomach and determination of serum gastrin and chromogranin A levels. Haematoxylin- and immunostaining with chromogranin A, gastrin and VMAT I and II (vesicular monoamine transporter I and II) of the biopsies were performed. RESULTS: Thirty-eight MEN1 patients, of whom 16 (42%) were diagnosed and treated earlier for ZES, were analysed. In ten of 16 (62.5%) ZES patients, a locally scattered, mixed image of diffuse, linear and micronodular mild hyperplasia was present. In addition, two of these patients (13%) showed small (max 1.5 mm in size) intramucosal ECL tumours. Neither ECL changes, nor tumours were found in MEN1 patients without ZES (n = 22). In MEN1/ZES patients, the median serum gastrin level was significantly elevated compared to MEN1 patients without ZES (206 pg/ml vs. 30.5 pg/ml, p < .001). A subgroup analysis of the serum gastrin and chromogranin A levels of MEN1/ZES patients with or without ECL hyperplasia did not show significant differences (gastrin level: p = .302, chromogranin A: p = .464). CONCLUSION: Enterochromaffin-like cell hyperplasia and gastric carcinoids occur only in MEN1 patients with ZES, but less frequently than reported.

Endoscopic ultrasound-fine needle biopsies of pancreatic lesions: Prospective study of histology quality using Franseen needle.

BACKGROUND: The introduction of fine needle biopsies (FNB) to clinical practice presents a changing trend towards histology in the endoscopic ultrasound-guided tissue acquisition (EUS-TA). AIM: To evaluate the clinical performance of a new FNB needle, the 22-gauge (22G) Franseen needle, when sampling pancreatic solid lesions. METHODS: Consecutive patients with an indication for EUS-TA for the assessment of pancreatic solid lesions were included in this prospective, single-center, single-arm trial. Each patient underwent a puncture of the lesion two times using the 22G Franseen needle and the obtained samples were directly placed into formalin for histological analysis. The primary study endpoint was the rate of high-quality obtained specimen. Secondary endpoints included the length and diameter of the core specimen, the diagnostic accuracy and the complication rate. RESULTS: From June 2017 to December 2018, forty patients with pancreatic solid lesions (22 females; mean age 67.2 years) were enrolled. Tissue acquisition was achieved in all cases. High-quality histology, rated with Payne score 3, was obtained in 37/40 cases (92.5%) after two needle passes. The mean size of the acquired histological core tissue was 1.54 mm × 0.39 mm. The diagnostic accuracy for the correct diagnosis was 85% (34/40). Only one adverse event was occurred, consisting of a self-limiting bleeding in the puncture site. CONCLUSION: The 22G Franseen needle achieved according to our standardized protocol a high rate of histological core procurement, and a high diagnostic accuracy, with one minor adverse event reported.

HEV-positive blood donations represent a relevant infection risk for immunosuppressed recipients.

BACKGROUND & AIMS: Routine HEV testing of blood products has recently been implemented in Great Britain and the Netherlands. The relevance of transfusion-transmitted HEV infections is still controversially discussed in Europe. METHODS: All blood donations at the University Medical Center Hamburg-Eppendorf were prospectively tested for HEV RNA by pooled PCR from October 2016 to May 2017. Reactive samples were individually retested. Additionally, stored samples from previous donations of positive donors were tested to determine the duration of HEV viraemia. HEV RNA-positive donors and a control cohort were asked to answer a questionnaire. RESULTS: Twenty-three out of 18,737 HEV RNA-positive donors were identified (0.12%). Only two of the positive donors (8.7%) presented with elevated aminotransferases at time of donation (alanine aminotransferase: 192 and 101 U/L). The retrospective analysis of all positive donors revealed that four asymptomatic donors had been HEV viraemic for up to three months with the longest duration of HEV viraemia exceeding four months. Despite the HEV-testing efforts, 14 HEV RNA-positive blood products were transfused into 12 immunocompromised and two immunocompetent patients. One recipient of these products developed fatal acute-on-chronic liver failure complicated by Pseudomonas septicemia. The questionnaire revealed that HEV RNA-positive donors significantly more often consumed raw pork meat (12 out of 18; 67%) than controls (89 out of 256; 35%; p = 0.01). In two donors, undercooked pork liver dishes were identified as the source of infection. HEV genotyping was possible in 7 out of 23 of HEV viraemic donors and six out of seven isolates belonged to HEV Genotype 3, Group 2. CONCLUSIONS: Prolonged HEV viraemia can be detected at a relatively high rate in Northern German blood donors, leading to transfusion-transmitted HEV infections in several patients with the risk of severe and fatal complications. Eating raw pork tartare represented a relevant risk for the acquisition of HEV infection. LAY SUMMARY: The relevance of transfusion-transmitted hepatitis E virus infections has been discussed controversially. Herein, we present the first report on routine hepatitis E virus screening of blood donations at a tertiary care centre in Germany. Hepatitis E viraemia was found at a relatively high rate of 0.12% among blood donors, which represents a relevant transfusion-related risk for vulnerable patient populations.

Prospective evaluation of the short access cholangioscopy for stone clearance and evaluation of indeterminate strictures.

BACKGROUND: Peroral cholangioscopy facilitates diagnosis and therapy of biliary disorders. This study prospectively evaluated a new short access cholangioscopy. METHODS: Consecutive patients were included as follows: difficult stones (group 1) underwent cholangioscopy with electrohydraulic lithotripsy and indeterminate biliary strictures (group 2) were evaluated with macroscopic assessment and cholangioscopy guided biopsy sampling. We evaluated the complete stone clearance rate (group 1) and diagnostic accuracy (group 2). Follow-up was performed over a median of 13 and 16 months, respectively. RESULTS: Group 1 (n=21): complete stone clearance defined as lack of stones in cholangiography and stone removal during cholangioscopy was achieved in 15 (71.4%) patients. Clinical stone clearance defined as lack of symptoms, laboratory abnormalities and hospital visits during follow-up, irrespective of stone clearance was evident in 17 (81.0%) patients. One serious adverse event occurred (bile duct perforation). Group 2 (n=28): malignancy was confirmed in 15 patients. Sensitivity, specificity and diagnostic accuracy of cholangioscopy were 85.7%, 75.0% and 80.7%, respectively. Sensitivity, specificity and diagnostic accuracy of biopsies were 54.5%, 100.0% and 72.2%, respectively. No serious adverse events occurred, and one patient was lost to follow-up. CONCLUSIONS: The novel system enabled complex stone treatment and biliary stricture diagnosis. Cholangioscopy outperformed direct biopsy regarding characterization of indeterminate strictures.

Early adverse events of per-oral endoscopic myotomy.

BACKGROUND AND AIMS: The recently developed technique of per-oral endoscopic myotomy (POEM) has been shown to be effective for the therapy of esophageal motility disorders. Limited information is available about POEM adverse events (AEs). METHODS: POEM was performed on 241 patients (58% male; mean age, 47.4 ± 16.4 years) under general anesthesia over 61 months. The main outcome was the rate of intra- and post-procedural AEs. Post-procedural checks comprised clinical and laboratory examinations and endoscopy, with further follow-ups performed at 3, 6, and 12 months. RESULTS: Of the 241 procedures, 238 were successfully completed (mean procedure time, 100.2 ± 39.5 min). Reasons for abortion were excessive submucosal fibrosis preventing submucosal tunneling. Three patients had severe procedural-related AEs (SAE rate, 1.2%); 1 case of pneumothorax required intra-procedural drainage, and 2 patients had delayed SAEs (1 ischemic gastric cardia perforation and 1 hemothorax, both leading to surgery). The overall rate of minor AEs was 31.1%, mainly prolonged intra-procedural bleeding (>15 min hemostasis) and defects of the mucosa overlying the tunnel; none led to clinically relevant signs or symptoms. Patients experiencing any AE had a significantly prolonged hospital stay (P = .037) and a trend toward prolonged procedure time (P = .094). Neck/upper thoracic emphysema and free abdominal air were noted in 31.5% and 35.7%, respectively (95.3% drained), but without relevant sequelae. CONCLUSIONS: POEM has a low rate of SAEs; minor AEs are more frequent but lack a consistent definition. Therefore, based on our experience and literature analysis, we suggest a classification of AEs for POEM. (Clinical trials registration number: NCT01405417.).