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 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.

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.

Effects of carbon dioxide insufflation during direct cholangioscopy on biliary pressures and vital parameters: a pilot study in porcine models.

BACKGROUND AND AIMS: Direct per-oral cholangioscopy allows endoscopic visualization of the biliary tract. Insufflation with carbon dioxide (CO2) is an alternative to saline solution irrigation during direct cholangioscopy. There are no data on maximal CO2 insufflation in direct cholangioscopy without causing biliary barotrauma or fatal gas embolism. We aimed to evaluate the safety of increasing CO2 insufflation in direct cholangioscopy without causing biliary barotrauma or fatal gas embolism. METHODS: This was an in vivo animal study. Four domestic pigs, under general endotracheal anesthesia, were used. The first animal was used to validate the feasibility of direct cholangioscopy and biliary pressure measurements, after which all animals underwent laparotomy, insertion of a pressure transducer in the cystic duct, and direct transpapillary placement of the cholangioscope. The common bile duct (CBD) and cystic duct were ligated to contain the instilled gas and exclusively expose the biliary tree. Insufflation of CO2 started at 200 mL/min and was continuously increased until there was evidence of bile duct rupture (as measured by a drop in intraductal pressures) or instability of vital signs (hypotension, bradycardia, bradypnea, O2 desaturation). Necropsy was performed on all animals to assess the liver and biliary system for evidence of barotrauma. RESULTS: CO2 was insufflated up to 8 L/min without causing bile duct rupture or instability in vital signs despite increasing CBD pressure with insufflation. There was significant correlation between CO2 flow with partial pressure of CO2 in arterial blood (PaCO2) (coefficient, 0.96-1.00; P < .01) and end tidal expired CO2 (EtCO2) (coefficient, 0.94-1.00; P < .01). However, the pulse rate, respiratory rate, arterial blood pressure, and O2 did not correlate with the amount of CO2 flow. There was no evidence of hepatic or biliary barotrauma on necropsy. CONCLUSIONS: This pilot experience in porcine models suggests that CO2 insufflation is safe for direct cholangioscopy and does not result in biliary barotrauma or vital signs instability.

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.

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.

Transcolonic peritoneoscopy by using submucosal endoscopy with mucosal flap for the detection of peritoneal bead targeting in the porcine survival model: a feasibility and effectiveness study.

BACKGROUND: Staging peritoneoscopy is typically done by laparoscopy in the operating room. Natural orifice transluminal endoscopic surgery peritoneoscopy is an appealing alternative to the current approach. Transcolonic submucosal endoscopy with mucosal flap (SEMF) may provide natural orifice transluminal endoscopic surgery peritoneoscopy. OBJECTIVE: The aim was to verify the feasibility and safety of transcolonic peritoneoscopy with SEMF (TCPS) in a porcine survival model. DESIGN: Survival study. SETTING: Animal research unit. INTERVENTION: Seven target beads were placed in the peritoneal cavity by laparoscopy in each of 6 animals, and TCPS was performed to identify and touch beads to simulate biopsy. Animals were euthanized after 1 week, at which time, laparotomy was performed and the SEMF site was resected for histological analysis. MAIN OUTCOME MEASUREMENTS: The number of beads identified and touched during peritoneoscopy, rate of successful completion of TCPS, procedure time, mortality equivalent 1 week after TCPS, adverse event rate, histological assessment of SEMF site. RESULTS: All 7 beads in all 6 pigs were identified and touched during TCPS. The success rate of TCP was 100%. No major adverse events occurred during the procedure. The median procedure times for the creation of a submucosal tunnel, peritoneoscopy, closure of mucosal incision, and entire procedure were 19.5, 17, 9.5, and 45 minutes, respectively. All pigs survived until euthanasia, and there was no evidence of peritonitis or severe infection. LIMITATIONS: Animal study, single endoscopist, small sample size. CONCLUSION: Results of this study indicate that TCPS is feasible and safe in a porcine survival model.

Submucosal endoscopy with mucosal resection (SEMR): a new hybrid technique of endoscopic submucosal balloon dissection in the porcine rectosigmoid colon.

BACKGROUND: We developed a technique, submucosal endoscopy with mucosal resection (SEMR) intended to make endoscopic submucosal dissection easier and safer. With this technique, the submucosal layer is balloon dissected in lieu of electrosurgical knife dissection. The aim of this study was to further evaluate SEMR in the porcine rectum and colon. METHODS: Targeted sites in the rectum and the distal colon were marked by spot coagulation. Submucosal fluid cushions (SFC) were created followed by a circumferential mucosal incision. After isolation of the targeted mucosa, balloon dissection was initiated. The balloon catheter was inserted deep into SFC and the inflated balloon repeatedly pulled back toward the endoscope tip to disrupt the submucosa. Residual strands of submucosa were cut. Dissection difficulty scores (DDS) were used using a visual analogue scale ranging from 0 to 5 (failed). The entire study period was divided into three periods (first period, pigs 1-10; second period, pigs 11-20; third period, pigs 21-30). RESULTS: Sixty lesions in 30 pigs were resected using SEMR. The en block resection rate was 95%. There were three incomplete resections, two as a result of an errant site location and one as a result of a floppy prototype balloon catheter tip. The median resected size, procedure time, and DDS were 6.0 cm, 25 min, and 1. All three failed cases occurred in first period. The procedure time in third period was significantly shorter than the second period (P = 0.0017). The DDS in first period was significantly higher than the second (P = 0.0024) and third (P = 0.0155) periods. Two perforations, one muscularis propria catheter perforation, and one mucosal perforation were observed (3.3%). CONCLUSIONS: Large mucosal target sites in the rectum and distal colon could be safely removed en bloc by means of a hybrid technique, SEMR, with blunt submucosal balloon dissection.

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.

Submucosal endoscopy with mucosal resection: a hybrid endoscopic submucosal dissection in the porcine rectum and distal colon.

BACKGROUND: Endoscopic submucosal dissection (ESD) has appeal for en bloc resection of large flat colorectal polyps but carries appreciable risk and demands a high level of expertise and training. Undermining flat and laterally spreading colorectal polyps by using submucosal endoscopy with the mucosal safety valve flap (SEMF) may be combined with ESD to offer a hybrid technique that is easier and safer. OBJECTIVE: To determine the feasibility of combining SEMF and ESD for the removal of progressively larger areas of the mucosa in the porcine rectum and colon. DESIGN: Two-phase ex vivo and in vivo study using domestic pig rectum and distal colon. SETTING: Developmental endoscopy unit/animal research unit. INTERVENTIONS: Progressively larger targeted mucosal dissections were performed by using the basic principles of ESD, which included margination of the targeted area of mucosa, submucosal fluid cushion, and needle-knife dissection. These were combined with the SEMF method of predissection with carbon dioxide (CO(2)) gas and balloon-based blunt dissection of the submucosa undermining the targeted and isolated mucosa. The hybrid technique was first applied to ex vivo porcine rectums and distal colons, then in vivo in an acute animal study. Progressively larger staged dissections were performed with 2-, 4-, and 6-cm diameter targeted mucosal sites. MAIN OUTCOME MEASUREMENTS: Success with associated difficulty or failure of the hybrid method in the rectum and distal colon to achieve complete resection of a progressively larger targeted area of mucosa. RESULTS: The ex vivo phase of the experiment demonstrated the ability to use the blunt balloon dissection of the SEMF procedure to remove 2-, 4-, and 6-cm areas of rectum and distal colon with a rapid progression to the largest size resection. The colon proximal to 20 cm above the anus was unable to hold a submucosal fluid cushion and allow submucosal dissection. Successful hybrid ESD was performed in vivo with staged progression through to the largest mucosal area (6 cm) within 20 cm of the anus. Dissections became progressively easier and faster to perform and dependent on the following steps: a traditional circumferential mucosal incision into the deep submucosa, an initial needle-knife submucosal "tunnel" dissection above the muscularis propria (MP), balloon dissection, and needle-knife release of persistent tethering strands of submucosa with and without vessels. Of 16 hybrid resections, 3 failures and 2 very difficult resections were attributed to attempts at resection too proximal in the colon, excessive flexibility of the balloon catheter, and electrosurgical device subperformance. There were no mucosal perforations or coagulation injuries to the MP. A single uninflated balloon catheter perforation of the MP occurred in a dissection site just above 20 cm from the anus with a suboptimal fluid cushion. LIMITATIONS: Animal study. Procedures performed by a single endoscopist with long-standing familiarity with the SEMF method. CONCLUSIONS: Large mucosal target sites in the rectum and distal colon of the pig can be safely removed en bloc by means of a hybrid technique, ie, submucosal endoscopy with mucosal resection, combining elements of ESD with our SEMF method.

Endoscopic "no hole" full-thickness biopsy of the stomach to detect myenteric ganglia.

BACKGROUND: The etiology of several common gastric motility diseases remains largely unknown. Gastric wall biopsy specimens that include the muscularis propria to evaluate the enteric nervous system, interstitial cells of Cajal, and related cells are essential to promote our understanding of the pathophysiologic mechanisms. On the basis of our previous work, a double EMR technique provided sufficient tissue to identify myenteric ganglia. A serious limitation to the technique was the resultant gastric wall perforation after tissue resection. The optimal procedure would seal the gastric wall defect before tissue resection, eliminating the risk of peritonitis. OBJECTIVES: The aims of this study were to (1) determine the technical feasibility and reproducibility of a full-thickness gastric biopsy by use of a novel double EMR technique without creating a perforation ("no hole") and to (2) determine safety of the procedure. DESIGN AND INTERVENTIONS: Preclinical study of 6 pigs. Each animal underwent a "no hole" double EMR survival procedure. To prevent perforation, detachable endoloops and prototype T-tag tissue anchors were placed before resection. At 2 weeks repeat endoscopy was performed followed by necropsy. MAIN OUTCOME MEASUREMENTS: Hematoxylin-eosin staining was used to determine which muscle layers were included in the resected specimen, and an antibody to neuronal nitric oxide synthase was used to visualize myenteric ganglia in the sample. Technical feasibility, reproducibility, and safety of the procedure were evaluated. RESULTS: Full-thickness gastric biopsy specimens were obtained from all animals without overt perforation. There were no procedural complications. Histologic examination showed muscularis propria with all layers of muscle present, and immunochemical studies demonstrated myenteric ganglia in all tissue samples. Four animals had an uneventful clinical course, and repeat endoscopy at week 2 showed ulceration with stellate fibrosis. Necropsy showed mild localized adhesions. Two animals were killed at days 3 and 6, respectively, because of suspected peritonitis. At necropsy, delayed perforations at the resection sites were noted with displaced endoloops and tissue anchors. CONCLUSION: This study explored the concept of obtaining deep muscle wall biopsy specimens with use of a unique approach of resection without perforation. The novel "no hole" double EMR technique was technically feasible and reproducible with sufficient tissue obtained to identify myenteric ganglia. However, there was a high delayed perforation rate associated with displaced endoloops and tissue anchors. On the basis of this early experience, improved safety data may be anticipated with future studies using improved tissue closure devices.

Pilot study of transesophageal endoscopic epicardial coagulation by submucosal endoscopy with the mucosal flap safety valve technique (with videos).

BACKGROUND: We previously demonstrated that the thoracic cavity could be safely accessed by submucosal endoscopy with the mucosal flap safety valve (SEMF) technique. OBJECTIVES: To evaluate the technical feasibility of transesophageal access to the heart and epicardial ablation. DESIGN: One-week survival study with 5 porcine models. SETTINGS: Animal laboratory with general anesthesia. INTERVENTIONS: High-pressure carbon dioxide injection and balloon dissection created a large submucosal working space for insertion of a cap-fitted endoscope. A myotomy was performed inside the submucosal space. The thoracic cavity was endoscopically accessed through the myotomy site. A pericardial window was created with a needle-knife. A spot coagulation of the epicardium was performed with a heat probe and a hook-knife. The myotomy site was sealed with the overlying mucosal flap, and the mucosal entry site was closed with clips. MAIN OUTCOME MEASUREMENTS: An endoscopy and a necropsy were performed to study the esophagus, mediastinum, pericardial space, and cautery locations on the epicardium one week after the procedure. RESULTS: Epicardial coagulation was successfully performed within 30 minutes in 4 of the 5 pigs. Follow-up endoscopy demonstrated completely sealed myotomy sites by the overlying mucosal flap. There was no gross contamination or signs of contamination in the thoracic cavity. The pericardial space was normal in appearance. The epicardial coagulation sites were healing, without exudative ulceration. CONCLUSIONS: The SEMF technique allowed endoscopic access to the upper mediastinum, the pericardium, and the epicardium via the esophagus, along with a minimal intervention on the epicardium.

Chemically assisted endoscopic mechanical submucosal dissection by using mesna.

BACKGROUND: A class of thiol compounds, mesna (sodium-2-mercaptoethanesulfonate), has been used to facilitate tissue dissection in surgical fields. OBJECTIVES: To evaluate the technical feasibility and efficacy of chemically assisted endoscopic mechanical submucosal dissection (CAEMSD) by using mesna. DESIGN: An in vivo controlled blind trial by using porcine models. SETTINGS: Nonsurvival study in an animal laboratory. INTERVENTIONS: Six pigs were studied. Mucosal targets of about 2 cm (estimated) for treatment were created with a circle of cauterized spots along the greater curvature of the gastric body and the antrum. A mesna solution or the control hydroxypropyl methylcellulose solution was submucosally injected. The target mucosa was mechanically isolated with balloon dissection and removed by circumferential incision with a hook-knife inserted into the submucosal space. Necropsy and mucosal specimens from both groups were examined by histology. RESULTS: En bloc resection of the target was achieved in all 8 attempts of the mesna group and in 7 of 8 attempts of the control group. Use of mesna significantly reduced tissue resistance to the initial balloon-catheter insertion into the submucosa and the technical difficulty of subsequent submucosal balloon dissection by using a subjective grading system (P < .05). There was no difference in histology between both groups. CONCLUSIONS: CAEMSD is a unique methodology to facilitate mucosal resection.

Mucosal atrophy in celiac disease: extent of involvement, correlation with clinical presentation, and response to treatment.

BACKGROUND & AIMS: Wireless capsule endoscopy provides an opportunity to study the macroscopic features in celiac disease by providing a magnified view of the intestinal mucosa. In this study, we evaluated the following: (1) the distribution of atrophy in untreated celiac disease, (2) the correlation between extent of changes and clinical manifestations, (3) the accuracy and interobserver agreement of wireless capsule endoscopy assessment, and (4) the effect of gluten withdrawal. METHODS: Thirty-eight consecutive patients with untreated biopsy-proven celiac disease underwent wireless capsule endoscopy. Each subject was invited to undergo repeat testing after at least 6 months of gluten withdrawal. The video images of each patient were reviewed independently by 2 investigators. RESULTS: Thirty-five (92%) subjects had visible atrophy detected by capsule endoscopy. Twenty-two (59%) subjects showed an extensive enteropathy, 12 (32%) had enteropathy limited to the duodenum, and only 1 had a jejunal enteropathy. No association was shown between the extent of the lesion and clinical manifestations. Capsule endoscopy had a better overall sensitivity for the detection of atrophy as compared with upper endoscopy (92% vs 55%, P = .0005), with a specificity of 100%. The overall interobserver agreement for the 2 reviewers was relatively high (% total agreement, 86.5%). After gluten withdrawal, the extent and the pattern of atrophy improved both qualitatively and quantitatively. CONCLUSIONS: Celiac disease affects a highly variable portion of the small intestine starting at the duodenum. The extent of visible enteropathy does not explain differences in clinical presentation. Most subjects with visually detected villous atrophy showed a clinically significant improvement after gluten withdrawal.

Evaluation of endoscopic approaches for deep gastric-muscle-wall biopsies: what works?

BACKGROUND: A major barrier to furthering our understanding of the pathophysiology of neuromuscular GI diseases, including functional GI disorders, is the inability to obtain deep gastric-wall biopsy specimens that include both layers of the muscularis propria, which allows evaluation of specific cell types, including myenteric ganglia. OBJECTIVES: The aims of this preclinical study were to (1) evaluate different endoscopic approaches for obtaining deep gastric-muscle-wall biopsy specimens and (2) determine if myenteric ganglia were present in the tissue samples. DESIGN AND INTERVENTIONS: This was a preclinical acute study by using a pig model. Multiple samples were obtained from 4 pigs. The endoscopic techniques evaluated were (1) EUS-guided tru-cut biopsy of the gastric wall, (2) jumbo biopsy of the post-EMR site, (3) jumbo biopsy of the gastrotomy margin, (4) serosal-side biopsy through a gastrotomy, and (5) double-EMR resection. MAIN OUTCOME MEASUREMENTS: Resected tissue was submitted for histology to determine which wall layers were included in the resected specimen. Hematoxylin and eosin staining was used to determine which muscle layers were biopsied, and an antibody to protein gene product 9.5 was used to determine if myenteric ganglia were present in the sample. RESULTS: Seventy-two tissue samples were obtained: EUS-guided tru-cut biopsy (n=16), jumbo biopsy of the post-EMR site (n=16), jumbo biopsy of the gastrotomy (n=16), serosal-side biopsy (n=16), and double-EMR resection (n=8). Only the double-EMR resection tissues showed the presence of longitudinal muscle, indicating the presence of both muscle layers and the myenteric plexus. Immunofluorescence studies demonstrated the presence of myenteric ganglia only in the double-EMR tissues and in none of the other gastric samples. No adjacent organs were included in the resection. CONCLUSIONS: The double-EMR technique was the only studied technique that resulted in a deep gastric-wall sample and provided sufficient tissue to evaluate both muscle layers and the intermuscular layer that contain myenteric ganglia. Further studies are needed to verify the efficacy and to assess the safety of this approach.

Transgastric cholecystectomy: transgastric accessibility to the gallbladder improved with the SEMF method and a novel multibending therapeutic endoscope.

BACKGROUND: Transgastric cholecystectomy is thought to technically and anatomically challenge a single entry flexible endoscopic approach. OBJECTIVES: To examine the feasibility of a transgastric-only cholecystectomy, endoscope performance in an upper-abdominal operation, and the usefulness of an offset gastrotomy. STUDY DESIGN: Animal survival study. SETTING: Animal research laboratory. PATIENTS: Six domestic pigs. MAIN OUTCOME MEASUREMENTS: Transgastric access to the gallbladder and technical feasibility of unassisted transgastric cholecystectomy. INTERVENTIONS: A cephalad submucosal tunnel was created in the anterior gastric wall with a high-pressure CO2 injection. An EMR-cap myotomy was performed distally within the submucosal space and created an offset gastrotomy. An endoscope was inserted into the peritoneal cavity through the myotomy. Access to the gallbladder was compared by using a multibending therapeutic endoscope (R-scope), with a standard double-channel endoscope. A cholecystectomy was performed by using both types of endoscopes. The myotomy site was sealed with the overlying mucosal flap. The mucosal entry point was closed with clips or tissue anchors. RESULTS: A standard double-channel endoscope could access the gallbladder in 2 of 4 attempts. A multibending endoscope accessed the gallbladder in all 4 attempts, including 2 pigs in which the standard scope failed to access the gallbladder. In 4 pigs, a cholecystectomy was completed. Two pigs died during surgery, with air embolization observed in 1. Two pigs survived a planned 1-week survival period. CONCLUSIONS: Transgastric cholecystectomy is technically feasible. Transgastric access to the gallbladder may be improved by using submucosal endoscopy with an offset exit gastrotomy by means of the mucosal flap safety-valve technique and a multibending gastroscope.

Transesophageal mediastinoscopy by submucosal endoscopy with mucosal flap safety valve technique.

BACKGROUND: Indications for NOTES (natural orifice transluminal endoscopic surgery) studied so far are limited to intra-abdominal surgery. OBJECTIVES: To determine the technical feasibility and the safety of transesophageal mediastinocosopy by using the submucosal endoscopy with mucosal flap safety valve (SEMF) technique. DESIGN: Two-week survival study with 4 porcine models. INTERVENTIONS: High-pressure carbon dioxide injection and balloon dissection created a large submucosal working space for insertion of a cap-fitted endoscope. The muscularis propria was resected inside the submucosal space, and the mediastinoscopy was performed by using the endoscope inserted via the myotomy site. The muscular defect was sealed with the overlying mucosal flap, and the mucosal entry site was closed with clips. MAIN OUTCOME MEASUREMENTS: Repeated endoscopy and necropsy were performed 2 weeks after the procedure. RESULTS: With the SEMF technique, the posterior mediastinum was successfully accessed in all animals. Three pigs survived 2 weeks without clinical complications, and the defects were completely sealed by the mucosal flap. One pig with proximal esophageal mediastinal entry managed under voluntary respiration was euthanized because of pleural injury. CONCLUSIONS: The SEMF technique provided safe entry into the mediastinum, with a protective submucosal tunnel that prevented mediastinal soiling. Mid to distal esophageal access is safer than the higher level access. Mechanical ventilation might allow safer respiratory support.

Submucosal endoscopy with mucosal flap safety valve.

BACKGROUND: There is no reliable endoscopic method to selectively resect deeper layers of the gut wall or to access the peritoneal cavity and prevent peritoneal soiling. OBJECTIVES: To determine the technical feasibility and safety of submucosal endoscopy with mucosal flap (SEMF) in accessing the peritoneal cavity through a large full-thickness gastric-muscle-wall resection. DESIGN: Ex vivo feasibility exploration and survival animal study. SETTINGS: Ex vivo samples were obtained from fresh harvested organs. In vivo procedures were conducted with the pigs under standard general anesthesia. INTERVENTIONS: High-pressure carbon dioxide (CO(2)) injection and balloon dissection created a large submucosal working space for insertion of a cap-fitted endoscope. By using the EMR cap, a full-thickness resection of the muscularis propria was performed. This full-thickness defect was sealed with the overlying mucosal flap and the use of hemoclips or tissue anchors. RESULTS: By using the SEMF technique in the ex vivo experiment, the gastric wall was successfully traversed in each stomach after submucosal dissection and full-thickness resection of the musclaris. Similarly, by using the SEMF technique in the in vivo procedures, the peritoneal cavity was successfully accessed and the defect was completely sealed by using the mucosal flap. All animals survived 1 week after the procedure. Ulceration was noted in 3 pigs, and a small bowel injury was noted in 1 pig. Leak testing was negative in all stomachs. CONCLUSIONS: By using the SEMF technique, submucosal space endoscopy and deep-layer gastric-wall resection were successfully performed. Furthermore, the mucosa overlying the dissected submucosal space served as a safe flap valve, preventing peritoneal leakage.