Vivek Kumbhari

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.

Human bile contains MicroRNA‐laden extracellular vesicles that can be used for cholangiocarcinoma diagnosis

Cholangiocarcinoma (CCA) presents significant diagnostic challenges, resulting in late patient diagnosis and poor survival rates. Primary sclerosing cholangitis (PSC) patients pose a particularly difficult clinical dilemma because they harbor chronic biliary strictures that are difficult to distinguish from CCA. MicroRNAs (miRs) have recently emerged as a valuable class of diagnostic markers; however, thus far, neither extracellular vesicles (EVs) nor miRs within EVs have been investigated in human bile. We aimed to comprehensively characterize human biliary EVs, including their miR content. We have established the presence of extracellular vesicles in human bile. In addition, we have demonstrated that human biliary EVs contain abundant miR species, which are stable and therefore amenable to the development of disease marker panels. Furthermore, we have characterized the protein content, size, numbers, and size distribution of human biliary EVs. Utilizing multivariate organization of combinatorial alterations (MOCA), we defined a novel biliary vesicle miR‐based panel for CCA diagnosis that demonstrated a sensitivity of 67% and specificity of 96%. Importantly, our control group contained 13 PSC patients, 16 with biliary obstruction of varying etiologies (including benign biliary stricture, papillary stenosis, choledocholithiasis, extrinsic compression from pancreatic cysts, and cholangitis), and 3 with bile leak syndromes. Clinically, these types of patients present with a biliary obstructive clinical picture that could be confused with CCA. Conclusion: These findings establish the importance of using extracellular vesicles, rather than whole bile, for developing miR‐based disease markers in bile. Finally, we report on the development of a novel bile‐based CCA diagnostic panel that is stable, reproducible, and has potential clinical utility. (Hepatology 2014;60:896–907)

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.

EUS-guided gastroenterostomy: the first U.S. clinical experience (with video)

BACKGROUND AND AIMS There are limitations to enteral self-expandable metal stents and surgical gastrojejunostomy in the treatment of patients with gastric outlet obstruction (GOO). EUS-guided gastroenterostomy (EUS-GE) is a novel procedure that potentially offers long-lasting luminal patency without the risk of tumor ingrowth and/or overgrowth, while avoiding the morbidity of a surgical procedure. The aims of this study were to report the first U.S. clinical experience with EUS-GE in terms of technical success, clinical success, and adverse events and to detail the technical aspects of performing EUS-GE. METHODS This was a retrospective study from two tertiary-care centers. EUS-GE was performed by using either the direct EUS-GE or balloon-assisted EUS-GE technique. Technical success was defined as adequate positioning and deployment of the stent as determined endoscopically and radiologically. Clinical success was defined as the patients ability to tolerate oral intake without vomiting. RESULTS A total of 10 patients underwent attempted EUS-GE. Malignant GOO was present in 3 patients, whereas benign obstruction was found in the remaining 7. One patient had complete GOO and underwent successful direct EUS-GE. In the remaining 9 patients, balloon-assisted EUS-GE was attempted and was successful in 8. Thus, technical success occurred in 9 patients (90%). There were no procedure-related adverse events. Mean procedure time was 96 minutes (range 45-152 minutes), and mean length of hospital stay was 2.2 days. Clinical success with resumption of solid oral intake was achieved in all 9 patients (100%) who underwent successful EUS-GE. A total of 8 patients were able to tolerate almost a normal diet and/or full diet, and 1 patient tolerated a soft diet. There was no symptom recurrence during a mean follow-up period of 150 days. CONCLUSIONS EUS-GE is a promising new technique for the treatment of symptoms of benign and malignant GOO. Prospective, multicenter trials are needed to confirm these results.

Refractory gastroparesis can be successfully managed with endoscopic transpyloric stent placement and fixation (with video).

BACKGROUND AND AIMS Medical treatment options for gastroparesis are limited. Data from studies of botulinum toxin and surgical pyloroplasty suggest that disruption of the pylorus can result in symptomatic improvement in some patients with refractory gastroparetic symptoms. The aim of this study was to determine the clinical response to transpyloric stent (TPS) placement in patients with gastroparetic symptoms refractory to standard therapy. METHODS Patients with gastroparesis refractory to medical treatment were referred for TPS placement for salvage therapy. Self-reported symptom improvement, stent migration rate, and pre- and post-stent gastric-emptying study results were collected. RESULTS A total of 30 patients with refractory gastroparesis underwent 48 TPS procedures. Of these, 25 of 48 (52.1%) were performed in patients admitted to the hospital with intractable gastroparetic symptoms. Successful stent placement in the desired location across the pylorus (technical success) was achieved during 47 procedures (98%). Most (n = 24) stents were anchored to the gastric wall by using endoscopic suturing with a mean number of sutures of 2 (range 1-3) per procedure. Clinical response was observed in 75% of patients, and all inpatients were successfully discharged. Clinical success in patients with the predominant symptoms of nausea and vomiting was higher than in those patients with a predominant symptom of pain (79% vs 21%, P = .12). A repeat gastric-emptying study was performed in 16 patients, and the mean 4-hour gastric emptying normalized in 6 patients and significantly improved in 5 patients. Stent migration was least common (48%) when stents were sutured. CONCLUSION TPS placement is a feasible novel endoscopic treatment modality for gastroparesis and improves both symptoms and gastric emptying in patients who are refractory to medical treatment, especially those with nausea and vomiting. TPS placement may be considered as salvage therapy for inpatients with intractable symptoms or potentially as a method to select patients who may respond to more permanent therapies directed at the pylorus.

Prevalence of adenomas and sessile serrated adenomas in Chinese compared with Caucasians

Colonic adenomas and sessile serrated adenomas (SSA) are the most common premalignant polyps identified at colonoscopy. This study compares the prevalence of neoplastic polyps in Chinese and Caucasians in a general gastroenterology outpatient practice in Australia.

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

Gastroesophageal reflux after peroral endoscopic myotomy: a multicenter case–control study

Background and study aims The variables associated with gastroesophageal reflux (GER) after peroral endoscopic myotomy (POEM) are largely unknown. This study aimed to: 1) identify the prevalence of reflux esophagitis and asymptomatic GER in patients who underwent POEM, and 2) evaluate patient and intraprocedural variables associated with post-POEM GER. Patients and methods All patients who underwent POEM and subsequent objective testing for GER (pH study with or without upper gastrointestinal [GI] endoscopy) at seven tertiary academic centers (one Asian, two US, four European) were included. Patients were divided into two groups: 1) DeMeester score ≥ 14.72 (cases) and 2) DeMeester score of < 14.72 (controls). Asymptomatic GER was defined as a patient with a DeMeester score ≥ 14.72 who was not consuming proton pump inhibitor (PPI). Results A total of 282 patients (female 48.2 %, Caucasian 84.8 %; mean body mass index 24.1 kg/m2) were included. Clinical success was achieved in 94.3 % of patients. GER evaluation was completed after a median follow-up of 12 months (interquartile range 10 - 24 months). A DeMeester score of ≥ 14.72 was seen in 57.8 % of patients. Multivariable analysis revealed female sex to be the only independent association (odds ratio 1.69, 95 % confidence interval 1.04 - 2.74) with post-POEM GER. No intraprocedural variables were associated with GER. Upper GI endoscopy was available in 233 patients, 54 (23.2 %) of whom were noted to have reflux esophagitis (majority Los Angeles Grade A or B). GER was asymptomatic in 60.1 %. Conclusion Post-POEM GER was seen in the majority of patients. No intraprocedural variables were identified to allow for potential alteration in procedural technique.

Similar Efficacies of Endoscopic Ultrasound Gallbladder Drainage With a Lumen-Apposing Metal Stent Versus Percutaneous Transhepatic Gallbladder Drainage for Acute Cholecystitis

Background & Aims Acute cholecystitis in patients who are not candidates for surgery is often managed with percutaneous transhepatic gallbladder drainage (PT‐GBD). Endoscopic ultrasound‐guided gallbladder drainage (EUS‐GBD) with a lumen‐apposing metal stent (LAMS) is an effective alternative to PT‐GBD. We compared the technical success of EUS‐GBD versus PT‐GBD, and patient outcomes, numbers of adverse events (AEs), length of hospital stay, pain scores, and repeat interventions. Methods We performed a retrospective study to compare EUS‐GBD versus PT‐GBD at 7 centers (5 in the United States, 1 in Europe, and 1 in Asia), from 2013 through 2015, in management of acute cholecystitis in patients who are not candidates for surgery. A total of 90 patients (56 men) with acute cholecystitis (61 calculous, 29 acalculous) underwent EUS‐GBD (n = 45) or PT‐GBD (n = 45). Data were collected on technical success, clinical success (resolution of symptoms or laboratory and/or radiologic abnormalities within 3 days of intervention), and need for repeat intervention. Characteristics were compared using Student t tests for continuous variables and the chi‐square test, or the Fisher exact test, when appropriate, for categorical variables. Adverse events were graded according to American Society for Gastrointestinal Endoscopy definitions and compared using the Fisher exact test. Postprocedure pain scores were compared using the Mann‐Whitney U test. Results Baseline characteristics, type, and clinical severity of cholecystitis were comparable between groups. In the EUS‐GBD group, noncautery LAMS were used in 30 patients and cautery‐enhanced LAMS were used in 15. Technical success was achieved for 98% of patients in the EUS‐GBD and 100% of the patients in the PT‐GBD group (P = .88). Clinical success was achieved by 96% of patients in the EUS‐GBD group and 91% in the PT‐GBD group (P = .20). There was a nonsignificant trend toward fewer AEs in the EUS‐GBD group (5 patients; 11%) than in the PT‐GBD group (14 patients; 32%) (P = .065). There were no significant differences in the severity of the AEs: mild, 2 in the EUS‐GBD group versus 5 in the PT‐GBD group (P = .27); moderate, 4 versus 3 (P = .98); severe, 1 versus 3 (P = .62); or deaths, 1 versus 3 (P = .61). The mean postprocedure pain score was lower in the EUS‐GBD group than in the PT‐GBD group (2.5 vs 6.5; P < .05). The EUS‐GBD group had a shorter average length of stay in the hospital (3 days) than the PT‐GBD group (9 days) (P < .05) and fewer repeat interventions (11 vs 112) (P < .05). The average number of repeat interventions per patients was 0.2 ± 0.4 EUS‐GBD group versus 2.5 ± 2.8 in the PT‐GBD group (P < .05). Median follow‐up after drainage was comparable in EUS‐GBD group (215 days; range, 1–621 days) versus the PT‐GBD group (265 days; range, 1–1638 days). Conclusions EUS‐GBD has similar technical and clinical success compared with PT‐GBD and should be considered an alternative for patients who are not candidates for surgery. Patients who undergo EUS‐GBD seem to have shorter hospital stays, lower pain scores, and fewer repeated interventions, with a trend toward fewer AEs. A prospective, comparative study is needed to confirm these results.

Efficacy and Safety of Peroral Endoscopic Myotomy for Treatment of Achalasia After Failed Heller Myotomy

BACKGROUND & AIMS: In patients with persistent symptoms after Heller myotomy (HM), treatment options include repeat HM, pneumatic dilation, or peroral endoscopic myotomy (POEM). We evaluated the efficacy and safety of POEM in patients with achalasia with prior HM vs without prior HM. METHODS: We conducted a retrospective cohort study of 180 patients with achalasia who underwent POEM at 13 tertiary centers worldwide, from December 2009 through September 2015. Patients were divided into 2 groups: those with prior HM (HM group, exposure; n = 90) and those without prior HM (non‐HM group; n = 90). Clinical response was defined by a decrease in Eckardt scores to 3 or less. Adverse events were graded according to criteria set by the American Society for Gastrointestinal Endoscopy. Technical success, clinical success, and rates of adverse events were compared between groups. Patients were followed up for a median of 8.5 months. RESULTS: POEM was technically successful in 98% of patients in the HM group and in 100% of patients in the non‐HM group (P = .49). A significantly lower proportion of patients in the HM group had a clinical response to POEM (81%) than in the non‐HM group (94%; P = .01). There were no significant differences in rates of adverse events between the groups (8% in the HM group vs 13% in the non‐HM group; P = .23). Symptomatic reflux and reflux esophagitis after POEM were comparable between groups. CONCLUSIONS: POEM is safe and effective for patients with achalasia who were not treated successfully by prior HM. Although the rate of clinical success in patients with prior HM is lower than in those without prior HM, the safety profile of POEM is comparable between groups.