Magnet-assist endoscopic augmentation of the lower esophageal sphincter for treatment of gastroesophageal reflux disease: cadaveric and survival studies in a porcine model (with video).

BACKGROUND: Augmentation of the lower esophageal sphincter (LES) is the primary goal of both surgical and endoscopic therapies for gastroesophageal reflux disease (GERD). The feasibility, efficacy, safety, and reversibility of a newly developed endotherapy for GERD using intraluminal magnets referred to as a magnet closure device (MCD) were evaluated. METHODS: This study involved nine cadaveric and six survival pigs. The MCD consisted of a ring neodymium magnet attached to a 2-0 polypropylene suture and suture anchor. The MCD was deployed onto the esophageal wall at the region of the LES using an endoscopic suturing device. Two to three MCDs were placed on opposing walls to induce closure of the esophageal lumen. LES pressures were measured using high-resolution manometry at the index procedure (baseline and immediately post-MCD placement) and at survival endoscopy. Endoscopic removal of the devices was performed followed by necropsy at week 2. RESULTS: MCDs were successfully deployed in all cadaveric (n = 22) and survival animals (n = 12). In cadavers, 20/22 (91%) sutures were full-thickness with no adjacent organ injury. In survival animals, mean LES pressure increased from 8.4 mmHg (baseline) to 32.4 mmHg immediately post-procedure (p < 0.01). No clinically significant adverse events occurred. Repeat endoscopy at two weeks showed intact MCDs in 4/6 (67%) animals with significant increase in median LES pressure (n = 4, 24.0 mmHg versus 7.4 mmHg [baseline], p < 0.05). Endoscopic removal of MCDs was successfully achieved. CONCLUSIONS: Endoscopic augmentation of the LES using a new MCD was feasible, safe and reversible with significantly increased LES pressures recorded. Future studies are needed to enhance durability. These preliminary results on a reversible technique are promising and may represent an attractive alternative to endoluminal GERD therapy.

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.

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.

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.

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.

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.

Endoscopic band ligation for closure of GI perforations in a porcine animal model (with video).

BACKGROUND: GI perforations occur rarely during endoscopy but have life-threatening implications. OBJECTIVE: To evaluate endoscopic band ligation (EBL) for closure of acute GI perforations by using a porcine model. DESIGN: Investigator-initiated interventional pilot study by using an in vivo porcine model. SETTING: Tertiary-care institution. SUBJECTS: Ten domestic pigs. INTERVENTION: Each animal underwent a single endoscopic procedure, with creation of a single GI lumen perforation. Perforations of 10 to 20 mm were created in the esophagus, stomach, duodenum, and colon. EBL was used for closure. Fourteen days later, the pigs were killed, microbial cultures were obtained, and histologic review was done. MAIN OUTCOME MEASUREMENTS: Immediate and delayed endoscopic closure of the perforation site, evidence of clinical peritonitis during the 14-day follow-up. RESULTS: Ten pigs completed the protocol and survived without clinical peritonitis during the 14-day follow-up. Endoscopic closure of a 15-mm esophageal perforation failed, thus, no attempt was made to close a 20-mm esophageal perforation. Closure of all other perforations was successful. At necropsy, fibrinous peritonitis was suspected in one animal with a 10-mm duodenal perforation. Chronic inflammation and fibroplasia at the perforation sites were the most common histologic findings. LIMITATIONS: The applicability of widespread use in humans remains unknown despite successful case reports in the medical literature. CONCLUSION: EBL can be used successfully to close 10 to 20 mm perforations within normal stomach, duodenum, and colon and can prevent clinically relevant intra-abdominal infections. However, for esophageal perforations, closure may be limited to small (≤10 mm), iatrogenic perforations.

Endoscopic full-thickness biopsy of the gastric wall with defect closure by using an endoscopic suturing device: survival porcine study.

BACKGROUND: The pathogenesis of several common gastric motility diseases and functional GI disorders remains essentially unexplained. Gastric wall biopsies that include the muscularis propria to evaluate the enteric nervous system, interstitial cells of Cajal, and immune cells can provide important insights for our understanding of the etiology of these disorders. OBJECTIVES: To determine the technical feasibility, reproducibility, and safety of performing a full-thickness gastric biopsy (FTGB) by using a submucosal endoscopy with mucosal flap (SEMF) technique; the technical feasibility, reproducibility, and safety of tissue closure by using an endoscopic suturing device; the ability to identify myenteric ganglia in resected specimens; and the long-term safety. DESIGN: Single center, preclinical survival study. SETTING: Animal research laboratory, developmental endoscopy unit. SUBJECTS: Twelve domestic pigs. INTERVENTIONS: Animals underwent an SEMF procedure with gastric muscularis propria resection. The resultant offset mucosal entry site was closed by using an endoscopic suturing device. Animals were kept alive for 2 weeks. MAIN OUTCOME MEASUREMENTS: The technical feasibility, reproducibility, and safety of the procedure; the clinical course of the animals; the histological and immunochemical evaluation of the resected specimen to determine whether myenteric ganglia were present in the sample. RESULTS: FTGB was performed by using the SEMF technique in all 12 animals. The offset mucosal entry site was successfully closed by using the suturing device in all animals. The mean resected tissue specimen size was 11 mm. Mean total procedure time was 61 minutes with 2 to 4 interrupted sutures placed per animal. Histology showed muscularis propria and serosa, confirming full-thickness resections in all animals. Myenteric ganglia were visualized in 11 of 12 animals. The clinical course was uneventful. Repeat endoscopy and necropsy at 2 weeks showed absence of ulceration at both the mucosal entry sites and overlying the more distal muscularis propria resection sites. There was complete healing of the serosa in all animals with minimal single-band adhesions in 5 of 12 animals. Retained sutures were present in 10 of 12 animals. LIMITATIONS: Animal experiment. CONCLUSIONS: FTGB by using the SEMF technique and an endoscopic suturing device is technically feasible, reproducible, and safe. Larger tissue specimens will allow improved analysis of multiple cell types.

Endoscopic full-thickness closure of large gastric perforations by use of tissue anchors.

BACKGROUND: A flexible needle-catheter tissue-anchoring device was developed to accomplish full-thickness tissue apposition of the GI wall. The aim of this study was to identify the performance of this device for repair of large iatrogenic gastric perforations in a porcine model. OBJECTIVES: Six pigs. DESIGN: Short-term survival animal study. SETTINGS: Pigs were studied while they were under general anesthesia. Device performance in differing gastric locations and wall thicknesses was assessed by 2 perforations more than 2 cm in size created for each pig along the greater curvature and the anterior wall. INTERVENTIONS: Each perforation was closed by parallel placement of tissue anchor sets sequentially along the length of the perforation. MAIN OUTCOME MEASUREMENTS: One week follow-up endoscopy and necropsy were performed. RESULTS: Twelve perforations were closed with the 48 tissue anchor sets. All animals survived for 1 week without clinical complications. Follow-up endoscopy and necropsy revealed that all tissue anchors remained with firmly held sutures and sealed perforations. CONCLUSIONS: Full-thickness closure with a new tissue-anchoring device simply and successfully repaired large iatrogenic gastric perforations.

Pilot study of the porcine uterine horn as an in vivo appendicitis model for development of endoscopic transgastric appendectomy.

BACKGROUND: Iatrogenic inflammation of the porcine uterine horn may serve as an in vivo appendicitis model for the development of endoscopic transgastric appendectomy. OBJECTIVE: Five female pigs. STUDY DESIGN: Animal study. SETTINGS: General anesthesia. MAIN OUTCOME MEASUREMENTS: Anatomical appearance and technical feasibility. INTERVENTIONS: Three pigs were used to identify an injectable material that would inflame the uterine horn, and 2 pigs were used for a pilot appendectomy. Three types of materials were individually injected into the bilateral uterine horns, and the ideal material to inflame the uterine horn was injected into the right uterine horn for the last 2 pigs. After 24 hours, the injected uterine horns of the first 3 pigs were assessed and a pilot appendectomy was performed in the last 2 pigs. RESULTS: Ethanolamine oleate (EO) injected uterine horns demonstrated similarities to the inflamed human appendix. Simulations of the appendectomy were successfully performed by using the EO model. LIMITATIONS: Suboptimal existing tools. CONCLUSIONS: This preliminary study demonstrated the technical feasibility to create a model for acute appendicitis by using the porcine uterine horn and transgastric appendectomy.