Endoscopic magnet placement into subadventitial tunnels for augmenting the lower esophageal sphincter using submucosal endoscopy: ex vivo and in vivo study in a porcine model (with video).

BACKGROUND AND AIMS: Endolumenal therapies serve as a treatment option for GERD. This study aimed to determine if magnets could be placed endoscopically using the adventitial layer to create a subadventitial space near the esophagogastric junction to augment the lower esophageal sphincter using submucosal endoscopy. METHODS: This study consisted of 2 phases, ex vivo and in vivo, with domestic pig esophagus. A long submucosal tunnel was made at the mid to lower esophagus. The muscularis propria was incised by a needle-knife within the submucosal tunnel. A subadventitial tunnel was made by biliary balloon catheter blunt dissection, and a magnet was deployed in the subadventitial space. The same maneuver was done within the opposing esophageal wall, with magnet placement in the opposing subadventitial space. RESULTS: Submucosal tunnels and subadventitial tunnels were successful without perforation ex vivo in all attempts and in 9 of 10 cases, respectively. Magnets were deployed in the subadventitial space in 7 cases. Magnets connected and separated with atraumatic endoscope passage into the stomach and reconnected when the endoscope was withdrawn under fluoroscopy in 5 of 7 cases (71.4%). In vivo submucosal tunnels and subadventitial tunnels were successful in all 5 cases, and magnet augmentation was functionally active in 4 cases (80%). CONCLUSION: Subadventitial tunnels were feasible and could represent a new working space for endoscopic treatment. Endoscopic placement of magnets within the subadventitial space may be an attractive alternative endolumenal therapy for GERD.

Patient-oriented education and visual-aid intervention are inadequate to identify patients with potential capsule retention: a prospective randomized study.

Background/aims: The key procedure-related risk with video capsule endoscopy (VCE) is capsule retention, which should be suspected in patients who have not reported capsule passage. The study aims were to determine the frequency of capsule passage visualization and the difference in self-reporting of capsule passage between patients who receive patient-oriented education (POE) and patients who receive POE and a visual aid intervention in the form of a wrist band (WB). Methods: This was a prospective randomized study that enrolled patients undergoing VCE. Patients were randomly assigned to a POE group versus a POE and WB group. POE consisted of verbal education and an information booklet. Both groups received instructions to notify the study team regarding capsule passage. Results: Sixty patients (mean age 57 ± 18 years; 61% female) were included. A total of 57 patients were included in the analysis (3 lost to follow-up; 28 in POE group; 29 in WB group). Capsule passage status was reported by 68% without significant difference between POE and WB groups (72% vs. 64%; p = .51). Capsule passage status was obtained from all 57 patients with the addition of a proactive follow-up. Only 56% (n = 32) reported visualizing capsule passage. Of the remaining patients who did not visualize capsule passage, 60% (n = 15) reported on this without significant difference between the POE and WB groups (p = .23). Conclusions: Lack of visualization of capsule passage is a poor indicator of retention. Self-reporting of VCE passage status is suboptimal and the addition of a visual aid did not improve this parameter.

Efficacy and safety of an internal magnet traction device for endoscopic submucosal dissection: ex vivo study in a porcine model (with video).

BACKGROUND: Appropriate traction allows for safer and easier endoscopic submucosal dissection (ESD). The aim of this study was to evaluate the efficacy and safety of an internal magnet traction device (MTD) for ESD in an ex vivo porcine model. METHODS: The MTD consisted of a small neodymium magnet and a suture attached to a through-the-scope clip. A circumferential mucosal incision was completed around a 30-mm diameter template that served as the target lesion. The first MTD was deployed at the proximal edge of the lesion. A second MTD was deployed on the wall opposite the lesion. With both magnets connected, this created traction or lifting of the target lesion towards the opposing wall during submucosal dissection. Primary endpoint was comparison of submucosal dissection times between conventional ESD (C-ESD) and MTD-assisted ESD (MTD-ESD). RESULTS: Twenty lesions along the anterior wall, posterior wall and greater curvature were resected using either C-ESD or MTD-ESD. The submucosal dissection time in MTD-ESD was significantly shorter than C-ESD (median: 6.4 [interquartile range {IQR} 4.6-8.7] min vs. 14.4 min [IQR 11.8-18.0], p < 0.05). There was a significant difference between MTD-ESD and C-ESD in total procedure times for lesions on the posterior gastric wall and greater curvature (median: 23.0 min [IQR 21.1-24.5] vs. 29.2 min [IQR 24.8-33.2], p < 0.05) with no difference for lesions on the anterior gastric wall (median: 18.8 min [IQR 15.5-20.5] vs. 17.1 min [IQR 13.1-20.0], p = 0.5). The number of muscularis propria injuries per lesion was significantly lower in MTD-ESD than C-ESD (median: 0 [IQR 0-0] vs. 1 [IQR 0-2], p < 0.05). CONCLUSIONS: MTD for ESD is effective and safe when compared to C-ESD. This approach significantly reduced submucosal dissection times with less injury to the muscularis propria. Furthermore, MTD-ESD was particularly beneficial for more challenging gastric lesions located on the posterior wall and greater curvature.

An internal magnet traction device reduces procedure time for endoscopic submucosal dissection by expert and non-expert endoscopists: ex vivo study in a porcine colorectal model (with video).

BACKGROUND: Efficacy of an internal magnet traction device (MTD) for gastric endoscopic submucosal dissection (ESD) by an expert endoscopist has been reported. We hypothesized that use of the MTD would enhance the performance of colorectal ESD in a non-expert endoscopist in ESD compared to the conventional technique. Primary aim of this study was to compare procedure times between conventional ESD (C-ESD) and MTD-assisted ESD (MTD-ESD) by expert and non-expert endoscopists in ESD. Secondary aims included rate of en bloc resection, iatrogenic injury, visualization score of the submucosal layer, and endoscopist satisfaction score. METHODS: A total of 56 lesions were created in an ex vivo porcine colorectum. Two endoscopists completed C-ESD (n = 28) and MTD-ESD (n = 28). Lesions measured 3 cm in diameter and were located on either the anterior or posterior colorectal wall. The MTD consisted of a small neodymium magnet and nylon monofilament attached to a through-the-scope clip. The first MTD was deployed on the opposing colorectal wall of the target lesion and a second MTD was then deployed directly onto the distal margin of the lesion. RESULTS: Total procedure time for MTD-ESD was significantly shorter than C-ESD for both expert (median: 15.8 vs. 19.3 min, p < 0.05) and non-expert (median: 21.3 vs. 33.9 min, p < 0.001) endoscopists. All lesions were resected en bloc. There was no iatrogenic muscularis propria injury in the MTD-ESD group. For both the expert and non-expert, scores for MTD-ESD were significantly higher for submucosal layer visualization (p < 0.05) and endoscopist satisfaction (p < 0.001) compared to C-ESD. CONCLUSIONS: Use of the MTD significantly reduced procedure time for both expert and non-expert endoscopists performing ESD. Improving the efficiency, safety, and satisfaction of ESD with such a device particularly for non-expert endoscopists is appealing and could potentially minimize the complexity and duration of the procedure allowing for more widespread use of the technique.

Single Fluid-Filled Intragastric Balloon Safe and Effective for Inducing Weight Loss in a Real-World Population.

BACKGROUND & AIMS: The Orbera intragastric balloon (OIB) is a single fluid-filled intragastric balloon approved for the induction of weight loss and treatment of obesity. However, little is known about the effectiveness and safety of the OIB outside clinical trials, and since approval, the Food and Drug Administration has issued warnings to health care providers about risk of balloon hyperinflation requiring early removal, pancreatitis, and death. We analyzed data on patients who have received the OIB since its approval to determine its safety, effectiveness, and tolerance in real-world clinical settings. METHODS: We performed a postregulatory approval study of the safety and efficacy of the OIB, and factors associated with intolerance and response. We collected data from the Mayo Clinic's database of patient demographics, outcomes of OIB placement (weight loss, weight-related comorbidities), technical aspects of insertion and removal, and adverse events associated with the device and/or procedure, from 8 centers (3 academic, 5 private, 4 surgeons, and 4 gastroenterologists). Our final analysis comprised 321 patients (mean age, 48.1 ± 11.9 y; 80% female; baseline body mass index, 37.6 ± 6.9). Exploratory multivariable linear and logistic regression analyses were performed to identify predictors of success and early balloon removal. Primary effectiveness outcomes were percentage of total body weight lost at 3, 6, and 9 months. Primary and secondary safety outcomes were rates of early balloon removal, periprocedural complications, dehydration episodes requiring intravenous infusion, balloon migration, balloon deflation or hyperinflation, pancreatitis, or other complications. RESULTS: Four patients had contraindications for placement at the time of endoscopy. The balloon was safely removed in all instances with an early removal rate (before 6 months) in 16.7% of patients, at a median of 8 weeks after placement (range, 1-6 mo). Use of selective serotonin or serotonin-norepinephrine re-uptake inhibitors at the time of balloon placement was associated with increased odds of removal before 6 months (odds ratio, 3.92; 95% CI, 1.24-12.41). Total body weight lost at 3 months was 8.5% ± 4.9% (n = 204), at 6 months was 11.8% ± 7.5% (n = 199), and at 9 months was 13.3% ± 10% (n = 47). At 6 months, total body weight losses of 5%, 10%, and 15% were achieved by 88%, 62%, and 31% of patients, respectively. Number of follow-up visits and weight loss at 3 months were associated with increased weight loss at 6 months (ß = 0.5 and 1.2, respectively) (P < .05). Mean levels of cholesterol, triglycerides, low-density lipoprotein, and hemoglobin A1c, as well as systolic and diastolic blood pressure, were significantly improved at 6 months after OIB placement (P < .05). CONCLUSIONS: In an analysis of a database of patients who received endoscopic placement of the OIB, we found it to be safe, effective at inducing weight loss, and to reduce obesity-related comorbidities in a real-world clinical population. Rates of early removal (before 8 weeks) did not differ significantly between clinical trials and the real-world population, but were affected by use of medications.

Endoscopic full-thickness resection using suture loop needle T-tag tissue anchors in the porcine stomach (with video).

BACKGROUND AND AIMS: Endoscopic full-thickness resection (EFTR) is still challenging, and a reliable technique is desirable. The aim of this study was to evaluate the feasibility of controlled EFTR using a pseudopolyp made from suture loop needle T-tag (SLNT) tissue anchors in ex vivo porcine stomachs. METHODS: Five pig stomachs were used. Two concentric circumferential border mucosal incisions were made to facilitate isolating a target lesion for full-thickness excision and pseudopolyp formation. SLNT tissue anchors were placed with a fishing line around the edges of the larger outer incision by endoscopic suturing. A suture pulley was created in the center of the targeted area and brought outside for traction. A large inverted pseudopolyp of the targeted lesion was made, visualizing apposing serosa with traction on the suture pulley while simultaneously cinching the encircling fishing line. EFTR was then performed on the isolated targeted tissue with the use of a needle-knife. RESULTS: Pseudopolyps were successful in all attempts. In the first attempt the encircling fishing line was cut, releasing the pseudopolyp during EFTR, with obvious leak. The remaining 4 EFTRs were performed with intact serosal apposing pseudopolyps and no air leaks. The median number of SLNT tissue anchors placed for a pseudopolyp was 5 (interquartile range, 4-5). The median size of full-thickness lesions was 37 mm (interquartile range, 29-49) and the median maximum pressure for the leak testing 9 mm Hg (interquartile range, 4-14) in the successful 4 attempts. CONCLUSION: This proof of principle study suggests that EFTR with SLNT-fashioned pseudopolyps is feasible.

Endoscopic muscle biopsy sampling of the duodenum and rectum: a pilot survival study in a porcine model to detect myenteric neurons.

BACKGROUND AND AIMS: Small bowel and colorectal muscle biopsy sampling requires a surgical approach. Advancing our understanding of the pathophysiology of motility disorders, such as functional bowel disorders, intestinal pseudo-obstruction, and slow-transit constipation, is hindered by our inability to noninvasively obtain muscularis propria (MP) for evaluation of multiple cell types, including myenteric neurons. The aims of this study were to determine (1) technical feasibility, reproducibility, and safety of performing duodenal endoscopic muscle biopsy sampling (dEMB) and rectal endoscopic muscle biopsy sampling (rEMB) using a clip-assist technique and (2) the presence of myenteric neurons in tissue samples. METHODS: Five 40-kg pigs were studied. Each animal underwent a dEMB and rEMB procedure. dEMB was performed using a single resection clip-assist technique. An over-the-scope clip was advanced to the duodenum. Tissue was suctioned into the cap and the clip deployed. The pseudopolyp of the duodenal wall created was then resected using snare electrocautery. rEMB was performed using a double resection clip-assist technique. EMR was initially performed to uncover the underlying MP using a band ligation technique. An over-the-scope clip was then advanced to the exposed MP. The MP was retracted and suctioned into the cap and the clip deployed. The pseudopolyp of the MP was resected using snare electrocautery. An antibody to protein gene product 9.5 was used to determine the presence of myenteric neurons in the samples. Animals were kept alive for 2 weeks, at which time an upper endoscopy and necropsy were performed. RESULTS: dEMB and rEMB were successfully performed in all animals with no procedural adverse events using this "no hole" (close then cut) approach. Mean procedure times for dEMB and rEMB were 23.7 ± 2.5 minutes and 13.25 ± 2.8 minutes, respectively. Mean length of resected full-thickness duodenal wall was 13.25 ± 4.3 mm and rectal MP was 12.5 ± 1.7 mm. Hematoxylin and eosin stain and antibody to protein gene product 9.5 confirmed the presence of MP with inner circular, outer longitudinal, and intermuscular layers, including myenteric neurons, in all samples. Clinical course was uneventful in all animals. Repeat upper endoscopy at 2 weeks showed well-healed dEMB sites. Necropsy in all animals showed no perforation, fluid collection, or abscess at the dEMB and rEMB sites. CONCLUSIONS: Based on this preclinical study, dEMB and rEMB appear to be technically feasible, reproducible, and safe. Sufficient MP tissue was obtained to identify myenteric neurons. These promising results are a step toward successful and safe implementation of these techniques into clinical practice for tissue diagnosis of muscle-based pathologies.

Large-caliber metal stents versus plastic stents for the management of pancreatic walled-off necrosis.

BACKGROUND AND AIMS: Symptomatic pancreatic walled-off necrosis (WON) may be managed by endoscopic transmural drainage and endoscopic transmural necrosectomy, with stent placement at endoscopic drainage sites. The optimal stent choice is yet to be determined. We compared outcomes after endoscopic management of WON using either large-caliber fully covered self-expandable metal stents (LC-SEMSs) or double-pigtail plastic stents (DPPSs). METHODS: We performed a retrospective comparison of outcomes among patients who received LC-SEMSs or DPPSs before endoscopic transmural necrosectomy for WON. RESULTS: Among 94 patients included, WON resolution rates did not differ between the DPPS (36 patients) and LC-SEMS (58 patients) groups, whether concomitant percutaneous drainage was considered a failure (75% vs 82.8%; P = .36) or not (91.7% vs 94.8%; P = .55). Of 75 patients (80%) successfully treated without percutaneous drainage, 37 (49%) underwent endoscopic transmural drainage without subsequent endoscopic transmural necrosectomy. WON was more likely to resolve without subsequent endoscopic transmural necrosectomy in the LC-SEMS group than the DPPS group (60.4% vs 30.8%; P = .01). WON resolution without subsequent endoscopic transmural necrosectomy remained more likely with LC-SEMSs (odds ratio, 4.5 [95% confidence interval, 1.5-15.5]) after adjusting for patient age and size and location of WON. Rates of adverse events were similar except for clinically significant bleeding requiring endoscopic intervention, which was higher with DPPSs than LC-SEMSs (14% vs 2%; P = .02). CONCLUSION: Management of pancreatic WON with LC-SEMSs appears to decrease both the need for repeated necrosectomy procedures and the risk of intervention-related hemorrhage.

Endoscopic sutured gastroplasty: procedure evolution from first-in-man cases through current technique.

BACKGROUND: Endoscopic sutured gastroplasty (ESG) has evolved over time. With the advent of full-thickness endoscopic suturing, an efficient technique for ESG was developed and refined. METHODS: This prospective first-in-man trial started in April 2012 and represents the first use of full-thickness endoscopic suturing for primary obesity therapy. The trial focused on procedure development, reproducibility, safety, and short-term efficacy. The trial was performed at centers in five countries, in three phases. Phase I was evaluation of safety and technical feasibility of various procedure techniques; stitch patterns and sequences were assessed for efficiency, safety, and feasibility. Phase II entailed continued procedure refinement to establish a standardized technique. Phase III entailed evaluation of technical feasibility and weight loss outcomes in 77 patients; the procedure was performed using the standardized technique, and there was no procedure development. Data were prospectively collected into a registry. RESULTS: In Phase I, the procedure was created and modified to improve time efficiency. Safety and technical feasibility were established, and short-term weight loss was demonstrated. In Phase II, a number of stitch patterns were attempted, and the stitch pattern was modified and finalized. 22 patients were included, and 1-year total weight loss was 17.3 ± 2.6%. In Phase III, conformity with the final technique was high. 77 patients were included, with a mean BMI of 36.1 ± 0.6 kg/m2. Mean weight loss was 16.0 ± 0.8% at 6 months and 17.4 ± 1.2% at 12 months (n = 44). Postprocedural nausea, vomiting, and epigastric pain were frequently reported; there were no reported significant adverse events post-procedure or during the follow-up period. CONCLUSIONS: Following a methodical procedure development phase, ESG demonstrated safety and short-term efficacy in this trial. The procedure also achieved meaningful weight loss during the follow-up period.

Transoral outlet reduction with full thickness endoscopic suturing for weight regain after gastric bypass: a large multicenter international experience and meta-analysis.

BACKGROUND AND AIMS: Many patients who undergo bariatric surgery will experience weight regain and effective strategies are needed to help these patients. A dilated gastrojejunal anastomosis (GJA) has been associated with weight recidivism after Roux-en-Y gastric bypass surgery (RYGB). Endoscopic transoral outlet reduction (TORe) with a full thickness endoscopic suturing device (Overstitch, Apollo Endosurgery, Austin, TX) is a minimally invasive therapeutic option. The primary aim of this project was to examine the safety and long-term efficacy data from three bariatric surgery centers and to conduct a systematic review and meta-analysis of the existing literature. METHODS: Patients who underwent TORe with the Overstitch device from Jan 2013 to Nov 2016 at 3 participating bariatric surgery centers were included in the multicenter analysis. For the systematic review and meta-analysis, a comprehensive search of multiple English databases was conducted. Random effects model was used. RESULTS: 130 consecutive patients across three centers underwent TORe with an endolumenal suturing device. These patients (mean age 47; mean BMI 36.8) had experienced 24.6% weight regain from nadir weight after RYGB. Average weight lost at 6, 12, and 18 months after TORe was 9.31 ± 6.7 kg (N = 84), 7.75 ± 8.4  kg (N = 70), 8 ± 8.8 kg (N = 46) (p < 0.01 for all three time points), respectively. The meta-analysis included 330 patients. The pooled weight lost at 12 months was 8.4 kg (95% CI 6.5-10.3) with no significant heterogeneity across included studies (p = 0.07). Overall, 14% of patients experienced nausea, 18% had pain and 8% required a repeat EGD. No serious adverse events reported. CONCLUSION: When implemented as part of a multidisciplinary intervention, TORe using endolumenal suturing is safe, reproducible, and effective approach to manage weight recidivism after RYGB and should be utilized early in the management algorithm of these patients.

Randomized controlled trial comparing submucosal endoscopy with mucosal resection and endoscopic submucosal dissection in the esophagus and stomach: Animal study.

BACKGROUND AND AIM: In Western countries, endoscopic submucosal dissection (ESD) has not prevailed as a result of training problems and a target patient population. We have previously reported a hybrid ESD technique, submucosal endoscopy with mucosal resection (SEMR), in which the submucosal dissection is carried out chiefly by blunt balloon dissection. We have also reported successful application in the porcine colon. In the present study, we compared the safety and efficacy of SEMR with ESD in the porcine esophagus and stomach. METHODS: SEMR and ESD were carried out in eight domestic pigs under general anesthesia. Resection sites were marked by circumferential coagulation. After circumferential ESD knife mucosal incision, submucosal fluid cushion (SFC) was created. In the SEMR group, the balloon catheter was inserted deep into the SFC. The balloon was then inflated and pulled back toward the endoscope tip repeatedly, altering the direction, to disrupt the submucosa. Residual strands were cut with an IT-knife. En bloc resection rates, procedure times, complications and dissection difficulty scales (DDS) were recorded prospectively. DDS were rated using a visual analog scale. RESULTS: Thirty-two resections (8 SEMR/8 ESD in the esophagus; 8 SEMR/8 ESD in the stomach) were done with no major adverse events. There was no statistical difference between the two techniques in either location in the above categories measured. CONCLUSIONS: SEMR and traditional ESD are comparable techniques in safety and effectiveness when carried out in the esophagus and stomach. SEMR may serve as a more appealing technical option for endoscopists who are unable to sustain a traditional ESD practice volume.

Endoscopic Sleeve Gastroplasty Alters Gastric Physiology and Induces Loss of Body Weight in Obese Individuals.

BACKGROUND & AIMS: Although bariatric surgery is the most effective therapy for obesity, only a small proportion of candidates undergo this surgery. Endoscopic sleeve gastroplasty (ESG) is a minimally invasive procedure that reduces the size of the gastric reservoir. We investigated its durability and effects on body weight and gastrointestinal function in a prospective study of obese individuals. METHODS: Twenty-five obese individuals (21 female; mean body mass index, 35.5 ± 2.6 kg/m2; mean age, 47.6 ± 10 years) underwent ESG with endoluminal creation of a sleeve along the gastric lesser curve from September 2012 through March 2015 at the Mayo Clinic in Rochester, Minnesota. Subjects were followed for a median period of 9 months. We measured changes in body weight and recorded adverse events; patients were assessed by endoscopy after 3 months. Four participants underwent pre-ESG and post-ESG analyses to measure solid and liquid gastric emptying, satiation (meal tolerance), and fasting and postprandial levels of insulin, glucose, and gut hormones. RESULTS: Subjects had lost 53% ± 17%, 56% ± 23%, 54% ± 40%, and 45% ± 41% of excess body weight at 6, 9, 12, and 20 months, respectively, after the procedure (P < .01). Endoscopy at 3 months showed intact gastroplasty in all subjects. After ESG, physiological analyses of 4 participants showed a decrease by 59% in caloric consumption to reach maximum fullness (P = .003), slowing of gastric emptying of solids (P = .03), and a trend toward increased insulin sensitivity (P = .06). Three patients had serious adverse events (a perigastric inflammatory collection, a pulmonary embolism, and a small pneumothorax) but made full recoveries with no need for surgical interventions. No further serious adverse events occurred after the technique was adjusted. CONCLUSIONS: ESG delays gastric emptying, induces early satiation, and significantly reduces body weight. ESG could be an alternative to bariatric surgery for selected patients with obesity. ClincialTrials.gov number: NCT 01682733.

Radiofrequency ablation for intraductal extension of ampullary neoplasms.

BACKGROUND AND AIMS: Extension of ampullary adenomas into the common bile duct (CBD) or pancreatic duct (PD) may be difficult to treat endoscopically. We evaluated the feasibility, safety, and efficacy of endoscopic radiofrequency ablation (RFA) in the management of ampullary neoplasms with intraductal extension. METHODS: This was a multicenter, retrospective analysis of all patients with intraductal extension of ampullary neoplasms treated with endoscopic RFA between February 2012 and June 2015. Treatment success was defined as the absence of detectable intraductal polyps by ductography, visual inspection, and biopsy sampling. RESULTS: Fourteen patients with adenoma extension into the CBD (13 ± 7 mm, n = 14) and PD (7 ± 2 mm, n = 3) underwent a median of 1 RFA sessions (range, 1-5). Additional modalities (thermal probes, argon plasma coagulation, and/or photodynamic therapy) were also used in 7 patients, and prophylactic stents were routinely placed. Thirteen assessable patients underwent a median of 2 surveillance ERCPs after completion of treatment over a median follow-up of 16 months (range, 5-46), with intraductal biopsy specimens showing no neoplasm in 12 patients at the conclusion of endoscopic treatment. Treatment success was achieved in 92%, including 100% of those treated with RFA alone. Adverse events occurred in 43% and included ductal strictures (5 patients) and retroduodenal abscess (1 patient), all of which were successfully treated endoscopically. CONCLUSIONS: Endoscopic RFA, alone or in combination with other modalities, may effectively treat intraductal extension of ampullary neoplasms. Ductal strictures were common after RFA but responded to endoscopic stent therapy. RFA may be appropriate in selected patients, particularly when the main treatment alternative is pancreaticoduodenectomy.

Innovative gastric endoscopic muscle biopsy to identify all cell types, including myenteric neurons and interstitial cells of Cajal in patients with idiopathic gastroparesis: a feasibility study (with video).

BACKGROUND AND AIMS: The pathophysiology of some GI neuromuscular diseases remains largely unknown. This is in part due to the inability to obtain ample deep gastric wall biopsies that include the intermuscular layer of the muscularis propria (MP) to evaluate the enteric nervous system, interstitial cells of Cajal (ICCs), and related cells. We report on a novel technique for gastric endoscopic muscle biopsy (gEMB). METHODS: Patients with idiopathic gastroparesis were prospectively enrolled in a feasibility study by using a novel "no hole" gEMB. Main outcome measures were technical success, adverse events, and histologic confirmation of the intermuscular layer, including myenteric neurons and ICC. The gEMB was a double resection clip-assist technique. A site was identified on the anterior wall of the gastric body as recommended by the International Working Group on histologic techniques. EMR was performed to unroof and expose the underlying MP. The exposed MP was then retracted into the cap of an over-the-scope clip. The clip was deployed, and the pseudopolyp of MP created was resected. This resulted in a no-hole gEMB. RESULTS: Three patients with idiopathic gastroparesis underwent gEMB. Patients had severe delayed gastric emptying with a mean (± standard deviation [SD]) of 49 ± 16.8% of retained gastric contents at 4 hours. They had no history of gastric or small-bowel surgery and did not use steroids or other immunosuppressive drugs. The gEMB procedure was successfully performed, with no procedural adverse events. Postprocedural abdominal pain was controlled with nonsteroidal anti-inflammatory agents and opioid analgesics. Mean length of resected MP was 10.3 ± 1.5 mm. Mean procedure time was 25.7 ± 6 minutes. Hematoxylin and eosin (H&E) staining of tissue samples confirmed the presence of both inner circular and outer longitudinal muscle, as well as the intermuscular layer. H&E staining showed reduced myenteric ganglia in 1 patient. In 2 patients, specialized immunohistochemistry was performed, which showed a marked decrease in myenteric neurons as delineated by an antibody to protein gene product 9.5 and a severe decrease in ICC levels across the muscle layers. At 1 month follow-up, upper endoscopy showed a well-healed scar in 2 patients and minimal ulceration with a retained clip in 1 patient. CT of the abdomen confirmed the integrity of the gastric wall in all patients. Because of lack of an immune infiltrate in the resected samples, patients were not considered suitable for immunosuppressive or steroid therapy. CONCLUSIONS: gEMB is feasible and easy to perform, with acquisition of tissue close to surgical samples to identify myenteric ganglia, ICCs, and multiple cell types. The ability to perform gEMB represents a paradigm shift in endoscopic tissue diagnosis of gastric neuromuscular pathologies.

Weekend Admission for Acute Cholangitis Does Not Adversely Impact Clinical or Endoscopic Outcomes.

BACKGROUND: Acute cholangitis (AC) requires prompt diagnosis and treatment for optimal management. AIMS: To examine whether a putative "weekend effect" impact outcomes of patients hospitalized for AC. METHODS: We conducted a retrospective study of patients admitted with AC between 2009 and 2012. After excluding those not meeting Tokyo consensus criteria for AC, the cohort was categorized into weekend (Saturday-Sunday) and weekday (Monday-Friday) hospital admission and endoscopic retrograde cholangiography (ERC) groups. Primary outcome was length of stay (LOS); secondary outcomes included ERC performance, organ failure, and mortality. Groups were compared with Chi-square and t tests; predictors of LOS were assessed with linear regression. RESULTS: The cohort consisted of 181 patients (mean age 63.1 years, 62.4 % male). Choledocholithiasis was the most common etiology of AC (29.4 %). Fifty-two patients (28.7 %) were admitted on a weekend and 129 (71.3 %) on a weekday. One hundred forty-one patients (78 %) underwent ERC, of which 120 (85 %) were on a weekday. There were no significant differences in baseline characteristics, LOS, proportion undergoing ERC, time to ERC, organ failure, or mortality between weekend and weekday admission groups. Similarly, there were no significant differences between weekend and weekday ERC groups. In multivariate analyses, international normalized ratio (p < 0.01) and intensive care unit triage (p < 0.01) were independent predictors of LOS, whereas weekend admission (p = 0.23) and weekend ERC (p = 0.74) were not. CONCLUSIONS: Weekend admission and weekend ERC do not negatively impact outcomes of patients hospitalized with acute cholangitis at a tertiary care center. Further studies, particularly in centers with less weekend resources or staffing, are indicated.

Endoscopic ultrasound (EUS)-guided coil injection therapy of esophagogastric and ectopic varices.

BACKGROUND: Endoscopic band ligation and glue injection are established techniques for variceal bleeding. As EUS may enhance variceal detection and improve therapeutic targeting, we aim to report our experience on EUS-guided coil embolization, with and without concomitant glue injection, of varices. METHODS: A prospectively maintained EUS database was retrospectively reviewed to identify consecutive patients who underwent EUS-guided variceal angiotherapy. All patients had failed or were poor candidates for standard endoscopic, surgical, or interventional radiologic therapies. The main outcome measurements were rates of rebleeding and adverse events. RESULTS: Fourteen patients [mean age 58 (SD 12) years, 50% male] underwent EUS-guided coil injection with (n = 4) or without (n = 10) concomitant glue injection to treat esophagogastric (n = 1), gastric (n = 5), duodenal (n = 3), or choledochal (n = 5) varices. Prior endoscopic and cross-sectional imaging detected only 57 and 64% of the varices seen. A mean of 5.1 (SD 1.9) coils and a median of 3.25 (range 2-3.5) mL of cyanoacrylate were injected during the initial procedure. During median follow-up of 12 (range 1-104) months, three patients died from unrelated causes and eight patients did not have further bleeding episodes. In the remaining three patients who had choledochal varices, the frequency and intensity of rebleeding decreased significantly. Only one asymptomatic adverse event occurred with coil migration to the liver. CONCLUSIONS: EUS-guided angiotherapy of varices is safe and feasible in selected patients who failed conventional therapy, and should be considered in the clinical management of these patients.

Efficacy of endoscopic ultrasound-guided hemostatic interventions for resistant nonvariceal bleeding.

A subset of patients with nonvariceal gastrointestinal bleeding fail, or are unsuitable candidates for, endoscopic, radiologic, and surgical interventions. Endoscopic ultrasound (EUS)-guided intervention might be effective in these patients. We performed EUS-guided hemostatic interventions for 17 patients with nonvariceal gastrointestinal bleeding from June 2003 through May 2014 who failed, or were unsuitable candidates for, additional therapies. Indications for treatment included gastrointestinal stromal tumors, colorectal vascular malformations, duodenal masses or polyps, Dieulafoy lesions, duodenal ulcers, rectally invasive prostate cancer, pancreatic pseudoaneurysms, ulcerated esophageal cancer, and ulceration after Roux-en-Y gastric bypass. After the procedure, 88% of patients have had no further bleeding related to the treated lesion, over a median follow-up period of 12 months. EUS-guided hemostatic therapy therefore is feasible and useful for select patients with clinically severe, refractory, or recurrent nonvariceal gastrointestinal bleeding.

Submucosal endoscopy as an aid to full-thickness resection: pilot study in the porcine stomach.

BACKGROUND: Endoscopic full-thickness resection (EFTR) is commonly performed with laparoscopic assistance. Submucosal endoscopy with full-thickness resection (SEFTR) is a new technique that combines submucosal endoscopy with the mucosal safety valve flap method to enable EFTR. OBJECTIVE: Pilot evaluation of the feasibility and safety of SEFTR in an animal model. DESIGN: In vivo animal study. SETTING: Developmental endoscopy unit/animal research unit. INTERVENTION: Five domestic pigs, under general anesthesia, were used. A 2-cm gastric target area was marked. A circumferential mucosal incision was made. Two parallel submucosal tunnels on opposite sides of the incision were made. The mucosa at the proximal and distal tunnel ends was cut. A suture was passed through the tunnels encircling the target. T bars with sutures were placed full thickness outside the target and brought out of the mouth. Pulling the oral sutures raised the target while the targeted area was cinched serosa to serosa with the encircling suture. Full-thickness excision was then performed without closure. MAIN OUTCOME MEASUREMENTS: Rate of adverse events, procedure times, adverse events, and difficulty scales were recorded prospectively. RESULTS: Circumferential mucosal incisions, submucosal tunnels, and connections were completed in all. In the first case, looping of the target lesion failed. In the remaining 4 cases, looping, cinching, and lifting were completed. Full-thickness resections were completed in 3 of 4 pigs. There were no procedural adverse events and no damage to adjacent organs. LIMITATIONS: Acute animal study. Procedures were performed by an endoscopist skilled in the submucosal endoscopy with the mucosal safety valve flap method. CONCLUSION: This pilot experience suggests that SEFTR is feasible and could be safe.

Randomized trial on the physiologic impact of NOTES.

BACKGROUND: Our previous work revealed significantly less acidosis in swine undergoing natural orifice translumenal endoscopic surgery (NOTES) using endoscopic air insufflation than swine undergoing standard laparoscopy. We wanted to evaluate the differential effects of CO2 versus intra-abdominal pressure as source for this finding. In addition, we investigated the endocrine stress response between swine undergoing NOTES peritoneoscopy with CO2 insufflation and animals undergoing standard diagnostic laparoscopy with CO2. MATERIALS AND METHODS: Twenty-eight (28) female 50-kg domestic pigs were randomly assigned to one of four groups using a permuted block randomization table: Group 1: NOTES using CO2 insufflation, Group 2: NOTES using air insufflation, Group 3: laparoscopy max pressure 12 mmHg and Group 4: laparoscopy with max pressure 7 mmHg. Invasive monitoring lines were placed. Pneumoperitoneum was established by the respective method and maintained for 90 min, visualizing liver, spleen and colon. Arterial blood gas was obtained at baseline and four additional time points. Serum TNF-α for POD (postoperative day) 1 and cumulative urine adrenaline for the procedure were determined by ELISA. ANOVA and t test were used for statistical comparison. The study was Institutional Animal Care and Use Committees approved. RESULTS: All experiments were completed as outlined. Blood pH showed a significant difference between groups. Serum TNF-α revealed higher levels for NOTES CO2 on POD 1 than standard laparoscopy (p = 0.03). CONCLUSION: NOTES animals with CO2 insufflation initially experienced similar pH compared to standard laparoscopy but recovered to levels seen in low-pressure laparoscopy and NOTES with air. NOTES with CO2 appears to elicit a stronger stress response in this study than standard or low-pressure laparoscopy or NOTES with air.

Cholangioscopy with narrow-band imaging in patients with primary sclerosing cholangitis undergoing ERCP.

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) have an increased lifetime risk of cholangiocarcinoma (CCA). Detection of localized CCA in patients with PSC may result in curative liver transplantation. Recently, high-resolution per-oral video cholangioscopy (PVCS) has become available and may be useful for evaluating for biliary dysplasia. Narrow-band imaging (NBI) has shown promising results in detecting dysplasia in the esophagus and colon, but its utility in the bile duct is unproven. OBJECTIVE: Evaluate NBI video PVCS in screening for dysplasia in patients with PSC. DESIGN: Prospective case series. SETTING: Tertiary-care referral center. PATIENTS: Patients with PSC undergoing ERCP between December 2008 and July 2010. INTERVENTION: ERCP with white-light and NBI PVCS and biopsy of suspicious lesions. MAIN OUTCOME MEASUREMENTS: Dysplasia detection. RESULTS: A total of 30 patients were enrolled. Median follow-up was 319.5 days. Four patients had a final diagnosis of CCA (2 extrahepatic, 2 intrahepatic). NBI visualized the 2 extrahepatic CCAs and allowed determination of tumor margins. The bile duct mucosa by NBI visual appearance in patients with PSC was variable. No correlation with CCA development could be determined. There was a 48% increase in suspicious lesions biopsied with NBI compared with white-light imaging, although NBI-directed biopsies did not improve the dysplasia detection rate. LIMITATIONS: Small sample size, single center, referral bias. CONCLUSION: NBI allowed visualization of tumor margins in CCA as compared with traditional fluoroscopy-based ERCP. An improvement in dysplasia detection in patients with PSC could not be demonstrated despite an increase in the biopsy rate. Additional experience is needed to assess the utility of NBI in screening for CCA in patients with PSC. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00951327.).