Peroral endoscopic myotomy: 10-year outcomes from a large, single-center U.S. series with high follow-up completion and comprehensive analysis of long-term efficacy, safety, objective GERD, and endoscopic functional luminal assessment.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is becoming the treatment of choice for achalasia. Data beyond 3 years are emerging but are limited. We herein report our 10-year experience, focusing on long-term efficacy and safety including the prevalence, management, and sequelae of postoperative reflux. METHODS: This was a single-center prospective cohort study. RESULTS: Six hundred ten consecutive patients received POEM from October 2009 to October 2019, 160 for type 1 achalasia (26.2%), 307 for type II (50.3%), 93 for type III (15.6%), 25 for untyped achalasia (4.1%), and 23 for nonachalasia disorders (3.8%). Two hundred ninety-two patients (47.9%) had prior treatment(s). There was no aborted POEM. Median operation time was 54 minutes. Accidental mucosotomies occurred in 64 patients (10.5%) and clinically significant adverse events in 21 patients (3.4%). No adverse events led to death, surgery, interventional radiology interventions/drains, or altered functional status. At a median follow-up of 30 months, 29 failures occurred, defined as postoperative Eckardt score >3 or need for additional treatment. The Kaplan-Meier clinical success estimates at years 1, 2, 3, 4, 5, 6, and 7 were 98%, 96%, 96%, 94%, 92%, 91%, and 91%, respectively. These are highly accurate estimates because only 13 patients (2%) were missing follow-up assessments. One hundred twenty-five patients (20.5%) had reflux symptoms more than once per week. At a median of 4 months, the pH study was completed in 406 patients (66.6%) and was positive in 232 (57.1%), and endoscopy was completed in 438 patients (71.8%) and showed reflux esophagitis in 218 (49.8%), mostly mild. CONCLUSIONS: POEM is exceptionally safe and highly effective on long-term follow-up, with >90% clinical success at ≥5 years.

Learning Curve for Endoscopic Submucosal Dissection With an Untutored, Prevalence-Based Approach in the United States.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is widely used in Asia to resect early-stage gastrointestinal neoplasms, but use of ESD in Western countries is limited. We collected data on the learning curve for ESD at a high-volume referral center in the United States to guide development of training programs in the Americas and Europe. METHODS: We performed a retrospective analysis of consecutive ESDs performed by a single operator at a high-volume referral center in the United States from 2009 through 2017. ESD was performed in 540 lesions: 449 mucosal (10% esophageal, 13% gastric, 5% duodenal, 62% colonic, and 10% rectal) and 91 submucosal. We estimated case volumes required to achieve accepted proficiency benchmarks (>90% for en bloc resection and >80% for histologic margin-negative (R0) resection) and resection speeds >9cm2/hr. RESULTS: Pathology analysis of mucosal lesions identified 95 carcinomas, 346 premalignant lesions, and 8 others; the rate of en bloc resection increased from 76% in block 1 (50 cases) to a plateau of 98% after block 5 (250 cases). The rate of R0 resection improved from 45% in block 1 to >80% after block 5 (250 cases) and ∼95% after block 8 (400 cases). Based on cumulative sum analysis, approximately 170, 150, and 280 ESDs are required to consistently achieve a resection speed >9cm2/hr in esophagus, stomach, and colon, respectively. CONCLUSIONS: In an analysis of ESDs performed at a large referral center in the United States, we found that an untutored, prevalence-based approach allowed operators to achieve all proficiency benchmarks after ∼250 cases. Compared with Asia, ESD requires more time to learn in the West, where the untutored, prevalence-based approach requires resection of challenging lesions, such as colon lesions and previously manipulated lesions, in early stages of training.

Per-oral endoscopic myotomy in patients with or without prior Heller's myotomy: comparing long-term outcomes in a large U.S. single-center cohort (with videos).

BACKGROUND AND AIMS: Heller's myotomy (HM) is one of the most effective treatments for esophageal achalasia. However, failures do exist, and the success rate tends to decrease with time. The efficacy of rescue treatments for patients with failed HM is limited. A few small-scale studies have reported outcomes of per-oral endoscopic myotomy (POEM) in these patients. We conducted this study to systematically assess feasibility, safety, and efficacy of POEM on patients who have had HM. METHODS: Patients at least 3 months out from POEM were selected from our prospective database: 318 consecutive POEMs performed from October 2009 to October 2016. The efficacy and safety of POEM were compared between the 46 patients with prior HM and the remaining 272 patients. RESULTS: Patients with prior HM had longer disease history, more advanced disease, more type I and less type II achalasia, lower before-POEM Eckardt scores, and lower before-POEM lower esophageal sphincter (LES) pressure (all P < .01). Procedure parameters and follow-up results (clinical success rate, Eckardt score, LES pressure, GERD score, esophagitis, and pH testing) showed no significant difference between the 2 groups. For the 46 HM-POEM patients, no clinically significant perioperative adverse events occurred. Their overall clinical success rate (Eckardt score ≤3 and no other treatment needed) was 95.7% at a median follow-up of 28 months. CONCLUSION: POEM as a rescue treatment for patients with achalasia who failed HM is feasible, safe, and highly effective. It should be the treatment of choice in managing these challenging cases at centers with a high level of experience with POEM.

The light at the end of the tunnel: a single-operator learning curve analysis for per oral endoscopic myotomy.

BACKGROUND: Per oral endoscopic myotomy (POEM) represents a natural orifice transluminal endoscopic surgery approach to Heller myotomy. Our center was the first to offer POEM outside of Japan, allowing us to accumulate what is likely the highest single-operator POEM volume in the United States. OBJECTIVE: To define the POEM learning curve of a gastroenterologist by using a larger data set and more detailed statistical analysis than used in 2 other reports of POEM performed by surgeons. DESIGN: Prospective cohort study. SETTING: Tertiary-care academic medical center. PATIENTS: We analyzed the first 93 consecutive POEMs on patients with achalasia aged >18 years without contraindications to POEM performed by a single operator from October 2009 to November 2013. INTERVENTIONS: (1) Efficiency estimation via cumulative sum (CUSUM) analysis, (2) mastery estimation via penalized basis-spline regression and CUSUM analysis, (3) correlation of operator experience with clinical outcomes (Eckardt score improvement, lower esophageal sphincter pressure reduction) and technical errors (accidental mucosotomy rate), and (4) unadjusted and adjusted regression analysis to assess how patient characteristics affected procedure time by using a generalized linear model. MAIN OUTCOME MEASUREMENTS: Clinical outcomes, procedure time, technical errors. RESULTS: Efficiency was attained after 40 POEMs and mastery after 60 POEMs. When we used the adjusted regression analysis, only case number (operator experience) significantly affected procedure time (P < .0001). Improvements in clinical outcomes were excellent but not significantly affected by operator experience, as was the case with accidental mucosotomies. Procedure time was not significantly affected by age, sex, achalasia stage, baseline lower esophageal sphincter pressure, baseline Eckardt score, prior treatment of achalasia, prior botulinum toxin injection, incidence of accidental mucosotomies, length of myotomy, or type of knife used (all P > .05). LIMITATIONS: Our analysis may underestimate the number of POEMs required to achieve mastery for operators with limited or no endoscopic submucosal dissection experience. CONCLUSION: These results offer thresholds for efficiency and mastery of a single gastroenterologist operator that may guide the efforts of novice POEM operators.

International multicenter experience with peroral endoscopic myotomy for the treatment of spastic esophageal disorders refractory to medical therapy (with video).

BACKGROUND: Limited data exist on the use of peroral endoscopic myotomy (POEM) for therapy of spastic esophageal disorders (SEDs). OBJECTIVE: To study the efficacy and safety of POEM for the treatment of patients with diffuse esophageal spasm, jackhammer esophagus, or type III (spastic) achalasia. DESIGN: Retrospective study. SETTING: International, multicenter, academic institutions. PATIENTS: All patients who underwent POEM for treatment of SEDs refractory to medical therapy at 11 centers were included. INTERVENTIONS: POEM. MAIN OUTCOME MEASUREMENTS: Eckardt score and adverse events. RESULTS: A total of 73 patients underwent POEM for treatment of SEDs (diffuse esophageal spasm 9, jackhammer esophagus 10, spastic achalasia 54). POEM was successfully completed in all patients, with a mean procedural time of 118 minutes. The mean length of the submucosal tunnel was 19 cm, and the mean myotomy length was 16 cm. A total of 8 adverse events (11%) occurred, with 5 rated as mild, 3 moderate, and 0 severe. The mean length of hospital stay was 3.4 days. There was a significant decrease in Eckardt scores after POEM (6.71 vs 1.13; P = .0001). Overall, clinical response was observed in 93% of patients during a mean follow-up of 234 days. Chest pain significantly improved in 87% of patients who reported chest pain before POEM. Repeat manometry after POEM was available in 44 patients and showed resolution of initial manometric abnormalities in all cases. LIMITATIONS: Retrospective design and selection bias. CONCLUSION: POEM offers a logical therapeutic modality for patients with SEDs refractory to medical therapy. Results from this international study suggest POEM as an effective and safe platform for these patients.

International multicenter experience with an over-the-scope clipping device for endoscopic management of GI defects (with video).

BACKGROUND: The over-the-scope clip (OTSC) provides more durable and full-thickness closure as compared with standard clips. Only case reports and small case series have reported on outcomes of OTSC closure of GI defects. OBJECTIVE: To describe a large, multicenter experience with OTSCs for the management of GI defects. Secondary goals were to determine success rate by type of defect and type of therapy and to determine predictors of treatment outcomes. DESIGN: Multicenter, retrospective study. SETTING: Multiple, international, academic centers. PATIENTS: Consecutive patients who underwent attempted OTSC placement for GI defects, either as a primary or as a rescue therapy. INTERVENTIONS: OTSC placement to attempt closure of GI defects. MAIN OUTCOME MEASUREMENTS: Long-term success of the procedure. RESULTS: A total of 188 patients (108 fistulae, 48 perforations, 32 leaks) were included. Long-term success was achieved in 60.2% of patients during a median follow-up of 146 days. Rate of successful closure of perforations (90%) and leaks (73.3%) was significantly higher than that of fistulae (42.9%) (P < .05). Long-term success was significantly higher when OTSCs were applied as primary therapy (primary 69.1% vs rescue 46.9%; P = .004). On multivariate analysis, patients who had OTSC placement for perforations and leaks had significantly higher long-term success compared with those who had fistulae (OR 51.4 and 8.36, respectively). LIMITATIONS: Retrospective design and multiple operators with variable expertise with the OTSC device. CONCLUSION: OTSC is safe and effective therapy for closure of GI defects. Clinical success is best achieved in patients undergoing closure of perforations or leaks when OTSC is used for primary or rescue therapy. Type of defect is the best predictor of successful long-term closure.

The International Per Oral Endoscopic Myotomy Survey (IPOEMS): a snapshot of the global POEM experience.

BACKGROUND: Per oral endoscopic myotomy (POEM) represents a Natural Orifice Transluminal Endoscopic Surgery (NOTES) approach to Heller myotomy. Even though we are now entering an exponential phase of growth with a large number of centers interested in POEM, published data to guide them are limited. As part of the July 2012 NOSCAR meeting, a conference was organized to review POEM and develop a consensus document. Authors SNS and TS who chaired the NOSCAR panel recognized the dearth of published data, which also may lag the rapid developments in POEM. Therefore, they undertook a survey of early POEM adopters around the world to rapidly obtain global, extensive, and current data on POEM. The raw survey data were made available to NOSCAR panel participants to assist with their presentations. We summarize the salient findings of the survey. METHODS: A comprehensive POEM survey was created and tested. The final survey instrument consisted of 197 questions that covered all aspects of POEM, including operator discipline, prior training, patient selection, setting, technique preference, results, adverse events, regulatory requirements, and perspectives on the future. An automated online response collector was used. RESULTS: The International Per Oral Endoscopic Myotomy Survey (IPOEMS) involved 16 expert centers, 7 in North America, 5 in Asia, 4 in Europe, including all high-volume centers (≥30 POEMs per center), as of July 2012. These centers had performed 841 POEMs. There were modest variations among centers in technique and periprocedural management, but all centers uniformly reported excellent efficacy and safety outcomes. CONCLUSIONS: The international POEM survey provides a "global snapshot" of the experience of early adopters. The excellent outcomes over a large cumulative volume of procedures are in line with those of published small series and lend further support to the notion that POEM represents a paradigm shift in the treatment of achalasia.

Endoscopic diverticulotomy for Killian-Jamieson diverticulum: mid-term outcome and description of an ultra-short tunnel technique.

Background and study aims Killian-Jamieson Diverticulum (KJD) is a rarer and more recently described upper pharyngeal diverticulum than Zenker's diverticulum (ZD). KJD is more difficult to manage than ZD because it tends to extend lower into the upper mediastinum and the diverticulum neck is in close proximity to the recurrent laryngeal nerve. There is limited literature on KJD management and transcervical surgical diverticulectomy is the mainstay of therapy. Patients and methods Here we describe two methods of endoscopic diverticulotomy to treat KJD - direct and tunneling diverticulotomy (with hypopharyngeal tunnel or ultra-short tunnel - the latter being our preferred technique). Results This was a retrospective study including 13 consecutive patients between March 2015 and April 2018. Three patients received direct and 10 received tunneling diverticulotomy (7 with the hypopharyngeal tunnel and 3 with the ultra-short tunnel). All procedures were completed in 16 to 52 minutes. There was no incidence of bleeding, mediastinitis, or sign of recurrent laryngeal nerve injury. At follow up of 9 to 79 months (median 33), the clinical success rate was 92 % (12/13); 11 patients had complete symptom resolution (post-operative symptom score = 0) and one patient had near-complete symptom resolution (occasional residual dysphagia). One patient receiving direct myotomy had limited symptom relief (frequent residual dysphagia and occasional residual regurgitation), possibly related to incomplete myotomy. Conclusions Endoscopic tunneling diverticulotomy is a feasible, safe, and effective method to treat KJD.

The appendix may protect against Clostridium difficile recurrence.

BACKGROUND & AIMS: Several risk factors have been identified for the development of recurrent Clostridium difficile infection (CDI) that alter host immunity and disrupt colonic flora. Although the function of the appendix has been debated, its active, gut-associated lymphoid tissue and biofilm production indicate potential roles in recovery from initial CDI and protection against recurrent CDI. We investigated whether the presence or absence of an appendix is associated with CDI recurrence. METHODS: We reviewed the medical records of adult inpatients with CDI who were admitted to a tertiary-care teaching hospital from 2005 to 2007 to identify those with and without an appendix. The primary dependent variable for statistical analysis was CDI recurrence. RESULTS: In a multivariate analysis of 11 clinical variables, the presence of an appendix was associated inversely with CDI recurrence (P < .0001; adjusted relative risk, .398). Age older than 60 years also was associated with CDI recurrence (P = .0280; adjusted relative risk, 2.44). CONCLUSIONS: The presence of an appendix has a significant and independent, inverse association with CDI recurrence, but this finding requires validation in a prospective study. Assessing the presence or absence of an appendix might be useful in predicting CDI recurrence.

International multicenter comparative trial of transluminal EUS-guided biliary drainage via hepatogastrostomy vs. choledochoduodenostomy approaches.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided biliary drainage (EUS-BD) can be performed entirely transgastrically (hepatogastrostomy/EUS-HG) or transduodenally (choledochoduodenostomy/EUS-CDS). It is unknown how both techniques compare. The aims of this study were to compare efficacy and safety of both techniques and identify predictors of adverse events. PATIENTS AND METHODS: Consecutive jaundiced patients with distal malignant biliary obstruction who underwent EUS-BD at multiple international centers were included. Technical/clinical success, adverse events, stent complications, and survival were assessed. RESULTS: A total of 121 patients underwent EUS-BD (CDS 60, HG 61). Technical success was achieved in 112 (92.56 %) patients (EUS-CDS 93.3 %, EUS-HG 91.8 %, P = 0.75). Clinical success was attained in 85.5 % of patients who underwent EUS-CDS group as compared to 82.1 % of patients who underwent EUS-HG (P = 0.64). Adverse events occurred more commonly in the EUS-HG group (19.67 % vs. 13.3 %, P = 0.37). Both plastic stenting (OR 4.95, 95 %CI 1.41 - 17.38, P = 0.01) and use of non-coaxial electrocautery (OR 3.95, 95 %CI 1.16 - 13.40, P = 0.03) were independently associated with adverse events. Length of hospital stay was significantly shorter in the CDS group (5.6 days vs. 12.7 days, P < 0.001). Mean follow-up duration was 151 ±â€Š159 days. The 1-year stent patency probability was greater in the EUS-CDS group [0.98 (95 %CI 0.76 - 0.96) vs 0.60 (95 %CI 0.35 - 0.78)] but overall patency was not significantly different. There was no difference in median survival times between the groups (P = 0.36) CONCLUSIONS: Both EUS-CDS and EUS-HG are effective and safe techniques for the treatment of distal biliary obstruction after failed ERCP. However, CDS is associated with shorter hospital stay, improved stent patency, and fewer procedure- and stent-related complications. Metallic stents should be placed whenever feasible and non-coaxial electrocautery should be avoided when possible as plastic stenting and non-coaxial electrocautery were independently associated with occurrence of adverse events.

Prospective international multicenter study on endoscopic ultrasound-guided biliary drainage for patients with malignant distal biliary obstruction after failed endoscopic retrograde cholangiopancreatography.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as an alternative to traditional radiologic and surgical drainage procedures after failed endoscopic retrograde cholangiopancreatography (ERCP). However, prospective multicenter data are lacking. The aims of this study were to prospectively assess the short- and long-term efficacy and safety of EUS-BD in patients with malignant distal biliary obstruction. PATIENTS AND METHODS: Consecutive patients at 12 tertiary centers (5 US, 5 European, 1 Asian, 1 South American) with malignant distal biliary obstruction and failed ERCP underwent EUS-BD. Technical success was defined as successful stent placement in the desired position. Clinical success was defined as a reduction in bilirubin by 50 % at 2 weeks or to below 3 mg/dL at 4 weeks. Adverse events were prospectively tracked and graded according to the American Society for Gastrointestinal Endoscopy (ASGE) lexicon's severity grading system. Overall survival and duration of stent patency were calculated using Kaplan-Meier analysis. RESULTS: A total of 96 patients (mean age 66 years, female 45 %, pancreatic cancer 55 %) underwent EUS-BD. Stent placement (technical success) was achieved in 92 (95.8 %) patients (metallic stent 84, plastic stent 8). Mean procedure time was 40 minutes. Clinical success was achieved in 86 (89.5 %) patients. A total of 10 (10.5 %) adverse events occurred: pneumoperitoneum (n = 2), sheared wire (n = 1), bleeding (n = 1), bile leak (n = 3), cholangitis (n = 2), and unintentional perforation (n = 1); 4 graded as mild, 4 moderate, 1 severe, and 1 fatal (due to perforation). A total of 38 (44 %) patients died of disease progression during the study period. The median patient survival was 167 days (95 %CI 112 - 221) days. The 6-month stent patency rate was 95 % (95 %CI 94.94 - 95.06 %) and the 1-year stent patency was 86 % (95 %CI 85.74 - 86.26 %). CONCLUSION: This study on EUS-BD demonstrates excellent efficacy and safety of EUS-BD when performed by experts. STUDY REGISTRATION: NCT01889953.

Peroral endoscopic myotomy (POEM) vs laparoscopic Heller myotomy (LHM) for the treatment of Type III achalasia in 75 patients: a multicenter comparative study.

BACKGROUND AND STUDY AIMS: Type III achalasia is characterized by rapidly propagating pressurization attributable to spastic contractions. Although laparoscopic Heller myotomy (LHM) is the current gold standard management for type III achalasia, peroral endoscopic myotomy (POEM) is conceivably superior because it allows for a longer myotomy. Our aims were to compare the efficacy and safety of POEM with LHM for type III achalasia patients. PATIENTS AND METHODS: A retrospective study of 49 patients who underwent POEM for type III achalasia across eight centers were compared to 26 patients who underwent LHM at a single institution. Procedural data were abstracted and pre- and post-procedural symptoms were recorded. Clinical response was defined by improvement of symptoms and decrease in Eckardt stage to ≤ 1. Secondary outcomes included length of myotomy, procedure duration, length of hospital stay, and rate of adverse events. RESULTS: Clinical response was significantly more frequent in the POEM cohort (98.0 % vs 80.8 %; P = 0.01). POEM patients had significantly shorter mean procedure time than LHM patients (102 min vs 264 min; P < 0.01) despite longer length of myotomy (16 cm vs 8 cm; P < 0.01). There was no significant difference between POEM and LHM in the length of hospital stay (3.3 days vs 3.2 days; P = 0.68), respectively. Rate of adverse events was significantly less in the POEM group (6 % vs 27 %; P < 0.01). CONCLUSIONS: POEM allows for a longer myotomy than LHM, which may result in improved clinical outcomes. POEM appears to be an effective and safe alternative to LHM in patients with type III achalasia.