Severity of post-ERCP pancreatitis directly proportional to the invasiveness of endoscopic intervention: a pilot study in a canine model.

BACKGROUND AND STUDY AIMS: Pancreatitis complicates 1% - 22% of endoscopic retrograde cholangiopancreatography procedures. The study aims were to develop a reproducible animal model of post-ERCP pancreatitis (PEP), and investigate the impact of endoscopic technique on severity of PEP. PATIENTS AND METHODS: ERCP was carried out in six male hound dogs. Pancreatitis was induced by one of three escalating methods: 1) pancreatic acinarization with 20 - 30 mL of contrast; 2) acinarization + ductal balloon occlusion + sphincterotomy; 3) acinarization + intraductal synthetic bile injection + ductal balloon occlusion + sphincterotomy. Dogs 5 and 6 received a pancreatic stent. Necropsy was performed on postoperative day 5. All pancreatic specimens were graded by two blinded pathologists according to a validated scoring system. All dogs were compared with three control dogs. RESULTS: Dogs 1 - 4 developed clinical pancreatitis and hyperamylasemia (11 736 vs. 722 U/L, P = 0.02). Total injury scores were significantly elevated compared with controls (6.85 vs. 1.06, P = 0.004). There was significant increase in acinar cell necrosis (0.86 vs. 0.06, P = < 0.001), and all other categories (except fibrosis) demonstrated elevated injury scores . Dogs 5 and 6 developed clinical pancreatitis without significant hyperamylasemia; total injury scores were elevated compared with controls (4.83 vs. 1.06, P = 0.01), but lower than in Dogs 1 - 4 (4.83 vs. 6.85, P = 0.25). There was escalating severity of pancreatic injury from Dogs 1 to 4 correlating with the method of endoscopic injury used. CONCLUSION: Severity of PEP is directly proportional to invasiveness of endoscopic intervention. Pancreatic acinarization, even without balloon occlusion and sphincterotomy, can be used as a reliable animal model for future studies investigating therapy and prevention of disease.

The utility of contrast-enhanced endoscopic ultrasound in monitoring ethanol-induced pancreatic tissue ablation: a pilot study in a porcine model.

BACKGROUND AND STUDY AIMS: Pancreatic ablation is gaining popularity for the treatment of focal pancreatic lesions. The aim of our study was to evaluate local effects of intrapancreatic alcohol injection and the utility of contrast-enhanced endoscopic ultrasound (EUS) for its monitoring in a porcine model. METHODS: We performed four survival experiments on 50-kg pigs. Under linear EUS guidance, 0.5 mL of 50% ethanol plus purified carbon particle solution (GI Spot) was injected into the pancreatic body to create a focal area of pancreatic necrosis. The animals survived for 24-48 hours (pigs # 1, # 2, and # 3) and 7 days (pig # 4). EUS was then repeated with and without perflutren lipid microspheres (Definity) administration through the peripheral vein. Standard and microsphere-enhanced images of the pancreas were compared. Afterwards the animals were euthanized for necropsy. RESULTS: Alcohol injection caused focal pancreatic necrosis, which was barely seen by standard EUS as a subtle hypoechoic lesion 1 cm in diameter. Color and power Doppler EUS of this region did not reveal any blood flow. After intravenous injection of microspheres, color Doppler EUS revealed marked contrast enhancement of normal pancreatic parenchyma with a clearly delineated avascular alcohol-treated area, which on postmortem examination corresponded to the discrete necrotic area marked with carbon particles. CONCLUSIONS: EUS-guided alcohol injection consistently causes focal areas of pancreatic necrosis. Contrast-enhanced EUS with microspheres improves visualization of altered pancreatic vascular perfusion and can be used to facilitate detection of small pancreatic lesions and its follow-up post-ablation.

Comparison of intraabdominal pressures using the gastroscope and laparoscope for transgastric surgery.

BACKGROUND: The peroral transgastric endoscopic approach for intraabdominal procedures appears to be feasible, although multiple aspects of this approach remain unclear. This study aimed to measure intraperitoneal pressure in a porcine model during the peroral transgastric endoscopic approach, comparing an endoscopic on-demand insufflator/light source with a standard autoregulated laparoscopic insufflator. METHODS: All experiments were performed with 50-kg female pigs under general anesthesia. A standard upper endoscope was advanced perorally through a gastric wall incision into the peritoneal cavity. The peritoneal cavity was insufflated with operating room air from an endoscopic light source/insufflator. Intraperitoneal pressure was measured by three routes: (1) through the endoscope biopsy channel, (2) through a 5-mm transabdominal laparoscopic port, and (3) through a 16-gauge Veress needle inserted into the peritoneal cavity through the anterior abdominal wall. The source of insufflation alternated between on-demand manual insufflation through the endoscopic light source/insufflator using room air and a standard autoregulated laparoscopic insufflator using carbon dioxide (CO(2)). RESULTS: Six acute experiments were performed. Intraperitoneal pressure measurements showed good correlation regardless of measurement route and were independent of the type of insufflation gas, whether room air or CO(2). On-demand insufflation with the endoscopic light source/insufflator resulted in a wide variation in pressures (range, 4-32 mmHg; mean, 16.0 +/- 11.7). Intraabdominal pressures using a standard autoregulated laparoscopic insufflator demonstrated minimal fluctuation (range, 8-15 mmHg; mean, 11.0 +/- 2.2 mmHg) around a predetermined value. CONCLUSION: Use of an on-demand unregulated endoscopic light source/insufflator for translumenal surgery can cause large variation in intraperitoneal pressures and intraabdominal hypertension, leading to the risk of hemodynamic and respiratory compromise. Safety may favor well-controlled intraabdominal pressures achieved with a standard autoregulated laparoscopic insufflator.

An endoscopically implantable device stimulates the lower esophageal sphincter on demand by remote control: a study using a canine model.

BACKGROUND AND STUDY AIMS: Implantable microstimulators (IMS) have been used in a variety of medical conditions. Selective stimulation to increase lower esophageal sphincter (LES) pressure may be useful in the control of gastroesophageal reflux disease. We evaluated on-demand stimulation of the LES with an endoscopically implanted microstimulator. MATERIALS AND METHODS: We performed acute experiments in three 30-kg dogs. After LES manometry, a 3.3 mm x 28 mm microstimulator (the Bion) was implanted into the LES. Manometry was repeated with and without IMS stimulation to record the changes in LES pressure. Stimulation amplitude was varied from 3 mA to 10 mA, with a fixed frequency of 20 Hz and a pulse width of 200 microsec. RESULTS: The mean LES pressures prior to IMS implantation in the three dogs were 13.0 mm Hg, 5.0 mm Hg, and 14.9 mm Hg. The mean pressures were not significantly changed by IMS placement. There were no documented changes in LES pressure when the amplitude of stimulation was less than 8 mA. After stimulation of the IMS at a setting of 10 mA in dogs 1 and 2 and at 8mA in dog 3, however, the resultant LES pressures were 62.1 mm Hg, 35.1 mm Hg, and 26.8 mm Hg respectively, more than three times higher than post-implantation baseline levels (P < 0.02). CONCLUSIONS: The LES pressure can be increased using an on-demand microstimulator. The implantation procedure is minimally invasive, represents a novel therapeutic approach to gastroesophageal reflux disease, and may have therapeutic potential for other gastrointestinal motility disorders.

Is blood the ideal submucosal cushioning agent? A comparative study in a porcine model.

BACKGROUND AND STUDY AIMS: Creation of a submucosal cushion before endoscopic mucosal resection (EMR) significantly reduces perforation risk. We evaluated six solutions as cushioning agents in live pigs. MATERIAL AND METHODS: 5 ml of normal saline, normal saline plus epinephrine, albumin 12.5 %, albumin 25 %, hydroxypropyl methylcellulose, and the pig's own whole blood were endoscopically injected into the porcine esophageal submucosa. Blood was obtained from a peripheral vein immediately before injection. Injections were made every 4 cm from the gastroesophageal junction. The time from completion of the injection to disappearance of the cushion was recorded. Endoscopy was repeated at 48 hours post injection. Two EMRs were performed after blood injection. Statistical analysis employed one-way analysis of variance followed by pairwise T test comparisons using the Bonferroni correction. RESULTS: Five animal experiments were completed. The mean time to dissipation of the submucosal cushion was shortest for saline plus epinephrine sites (2.87 minutes, SD 2.21) followed by the saline (4.8 minutes, SD 1.56), albumin 12.5 % (5.68 minutes, SD 3.48), albumin 25 % (7.83 minutes, SD 2.02), hydroxypropyl methylcellulose (9.77 minutes, SD 1.55), and blood sites (38.6 minutes, SD 6.07). Injection of blood resulted in significantly longer mucosal elevation than any other solution ( P < 0.0007). Blood from the cushion did not hamper visualization and facilitated EMR. CONCLUSION: Blood produces the most durable cushion compared with standard agents, also having the advantages of being readily available and without cost. Albumin 25 % provides as durable a cushion as hydroxypropyl methylcellulose.

Transgastric endoscopic splenectomy: is it possible?

BACKGROUND: We have previously reported the feasibility of diagnostic and therapeutic peritoneoscopy including liver biopsy, gastrojejunostomy, and tubal ligation by an oral transgastric approach. We present results of per-oral transgastric splenectomy in a porcine model. The goal of this study was to determine the technical feasibility of per-oral transgastric splenectomy using a flexible endoscope. METHODS: We performed acute experiments on 50-kg pigs. All animals were fed liquids for 3 days prior to procedure. The procedures were performed under general anesthesia with endotracheal intubation. The flexible endoscope was passed per orally into the stomach and puncture of the gastric wall was performed with a needle knife. The puncture was extended to create a 1.5-cm incision using a pull-type sphincterotome, and a double-channel endoscope was advanced into the peritoneal cavity. The peritoneal cavity was insufflated with air through the endoscope. The spleen was visualized. The splenic vessels were ligated with endoscopic loops and clips, and then mesentery was dissected using electrocautery. RESULTS: Endoscopic splenectomy was performed on six pigs. There were no complications during gastric incision and entrance into the peritoneal cavity. Visualization of the spleen and other intraperitoneal organs was very good. Ligation of the splenic vessels and mobilization of the spleen were achieved using commercially available devices and endoscopic accessories. CONCLUSIONS: Transgastric endoscopic splenectomy in a porcine model appears technically feasible. Additional long-term survival experiments are planned.