Inspection of the human stomach using remote-controlled capsule endoscopy: a feasibility study in healthy volunteers (with videos).

BACKGROUND: Remote control of capsule endoscopes might allow reliable inspection of the human stomach. OBJECTIVE: To assess the safety and efficacy of manipulation of a modified capsule endoscope with magnetic material (magnetic maneuverable capsule [MMC]) in the human stomach by using a handheld external magnet. DESIGN: Open clinical trial. SETTING: Academic hospital. PATIENTS: Ten healthy volunteers. INTERVENTIONS: Subjects swallowed the MMC and sherbet powder for gastric distention. An external magnetic paddle (EMP-2) was used to manipulate the MMC within the stomach. MMC responsiveness was evaluated on a screen showing the MMC film in real time. MAIN OUTCOME MEASUREMENTS: Safety and tolerability (questionnaire), gastric residence time of the MMC, its responsiveness to the EMP-2, area of gastric mucosa visualized. RESULTS: There were no adverse events. The MMC was always clearly attracted by the EMP-2 and responded to its movements. It remained in the stomach for 39 ± 24 minutes. In 7 subjects, both the cardia and the pylorus were inspected and 75% or more of the gastric mucosa was visualized (≥50% in all of the remaining subjects). A learning curve was clearly recognizable (identification of MMC localization, intended movements). LIMITATIONS: Small amounts of fluid blocked the view of apical parts of the fundus; gastric distention was not sufficient to flatten all gastric folds. CONCLUSIONS: Remote control of the MMC in the stomach of healthy volunteers using a handheld magnet is safe and feasible. Responsiveness of the MMC was excellent, and visualization of the gastric mucosa was good, although not yet complete, in the majority of subjects. The system appeared to be clinically valuable and should be developed further. ( CLINICAL TRIAL REGISTRATION NUMBER: DE/CA05/2009031008.).

Remote magnetic control of a wireless capsule endoscope in the esophagus is safe and feasible: results of a randomized, clinical trial in healthy volunteers.

BACKGROUND: Remote control of esophageal capsule endoscopes could enhance diagnostic accuracy. OBJECTIVE: To assess the safety and efficacy of remote magnetic manipulation of a modified capsule endoscope (magnetic maneuverable capsule [MMC]; Given Imaging Ltd, Yoqneam, Israel) in the esophagus of healthy humans. DESIGN: Randomized, controlled trial. SETTING: Academic hospital. PATIENTS: This study involved 10 healthy volunteers. INTERVENTION: All participants swallowed a conventional capsule (ESO2; Given Imaging) and a capsule endoscope with magnetic material, the MMC, which is activated by a thermal switch, in random order (1 week apart). An external magnetic paddle (EMP; Given Imaging) was used to manipulate the MMC within the esophageal lumen. MMC responsiveness was evaluated on a screen showing the MMC film in real time. MAIN OUTCOME MEASUREMENTS: Safety and tolerability of the procedure (questionnaire), responsiveness of the MMC to the EMP, esophageal transit time, and visualization of the Z-line. RESULTS: No adverse events occurred apart from mild retrosternal pressure (n = 5). The ability to rotate the MMC around its longitudinal axis and to tilt it by defined movements of the EMP was clearly demonstrated in 9 volunteers. Esophageal transit time was highly variable for both capsules (MMC, 111-1514 seconds; ESO2, 47-1474 seconds), but the MMC stayed longer in the esophagus in 8 participants (P < .01). Visualization of the Z-line was more efficient with the ESO2 (inspection of 73% ± 18% of the circumference vs 33% ± 27%, P = .01). LIMITATIONS: Magnetic forces were not strong enough to hold the MMC against peristalsis when the capsule approached the gastroesophageal junction. CONCLUSION: Remote control of the MMC in the esophagus of healthy volunteers is safe and feasible, but higher magnetic forces may be needed.

A hinged metalloplastic anastomotic device: a novel method for choledochoduodenostomy.

BACKGROUND: In biliary obstruction, the creation of a large-diameter permanent fistula between the bile duct and the duodenum would be attractive. OBJECTIVE: To invent, prototype, and test a new method of forming a biliary duodenal anastomosis. DESIGN: Survival and nonsurvival porcine model. SETTING: An animal laboratory with general anesthesia. INTERVENTION: A novel hybrid metalloplastic 7F anastomosis device that consisted of a central ferrous metallic tube sandwiched between 2 tapered flexible plastic end pieces was used. The device was hinged on either side of the metal insert so that a magnetic force could form an anastomosis and then the plastic components of the device could deform to fall through the compression anastomosis. These devices were inserted into the bile duct of the pigs over a 0.035-inch guidewire with a pusher tube. Cylindrical-shaped magnets were then positioned over the intraduodenal bile duct so that they exerted compressive ischemic force on the duodenum and bile duct above the papilla. MAIN OUTCOME MEASUREMENTS: Choledochoduodenal anastomoses created were inspected at subsequent endoscopy and postmortem for patency and size. RESULTS: Seven anastomosis devices were placed in the bile duct of pigs (weight 22-54 kg). All 4 survival animals were well and eating as soon as they were awake. Anastomoses were successfully accomplished in all survival animals. The supra-ampullary opening into the bile duct ranged from 5 to 10 mm. LIMITATION: The small number of animals. CONCLUSIONS: A new method for achieving larger-diameter biliary drainage was developed. Four animals were euthanized after 2 to 7 days. Our best anastomosis resulted from 2 magnets left in the animals for 4 days.

Photodynamic therapy of malignant biliary strictures using meso-tetrahydroxyphenylchlorin.

OBJECTIVES: The palliation of patients with malignant bile duct obstruction using metal or plastic biliary stents may be limited by stent occlusion. The aim of this study was to determine the safety and efficacy of endoscopically delivered meso-tetrahydroxyphenyl chlorin photodynamic therapy in the treatment of irresectable malignant biliary strictures and recurrent stent occlusion. METHODS: Thirteen patients with malignant biliary obstruction owing to carcinoma of the biliary tract (n=9), pancreas (n=3) or stomach (n=1), were studied. All had been initially palliated with metal (n=10) or polyethylene (n=3) biliary stents, but presented with recurrent obstructive jaundice because of local tumour progression. Patients received meso-tetrahydroxyphenyl chlorin 0.15 mg/kg intravenously 72 h before endoluminal light activation with an endoscopically placed optical fibre, followed by polyethylene stent insertion. RESULTS: Before photodynamic therapy, patients had a median of three (range 0-5) stent occlusions in the preceding 11 (2-22) months, with a median patency of plastic stents placed inside metal bile duct stents for recurrent stent occlusion of 3.5 (0.5-13) months. After photodynamic treatment, tumour necrosis and/or metal stent recanalization was seen in all patients, with a median of 0 (0-3) stent occlusions during 7 (1-43) months follow-up. The median patency of plastic stents placed inside metal stents after photodynamic therapy was 5 (1-43) months. The median survival after diagnosis and photodynamic therapy administration was 21 (10-56) and 8 (1-43) months, respectively. Photodynamic therapy was generally well tolerated but two patients developed cholangitis within the first week, complicated in one by a fatal liver abscess and two developed haemobilia within 4 weeks of treatment, one of whom died with a gall bladder empyema. CONCLUSION: In patients with malignant biliary obstruction, endoscopically delivered meso-tetrahydroxyphenyl chlorin photodynamic therapy causes efficient tumour necrosis and recanalization of blocked metal stents, but there is a significant risk of complications.

Intracellular re-localisation by photochemical internalisation enhances the cytotoxic effect of gelonin--quantitative studies in normal rat liver.

Photochemical internalisation (PCI) is a delivery technology that employs a sub-lethal form of photodynamic therapy (PDT) in which a photosensitiser is activated by light to break down intracellular membranes and release macromolecules into the cytosol where they can be biologically active. Although PCI does enhance the PDT killing of transplanted tumours in mice after local injection of the cytotoxic agent, gelonin, the redistribution of gelonin from intracellular organelles into the cytosol has only previously been demonstrated in vitro. This study is designed to understand the factors controlling the efficacy of PCI in vivo and to document the mechanism of action. Using the photosensitiser AlS(2)Pc in studies on normal rat liver, we have demonstrated in vivo that gelonin is initially taken up into lysosomes, but can be released into the cytosol using PCI. Furthermore, PCI enhances the PDT effect after systemic administration of gelonin (volume of necrosis increased x2.5 when gelonin is given one hour before light), with the remarkably low dose of 5 microg/kg (10,000 times lower than the LD50); in the absence of light, there is no effect with 500 microg/kg. These results suggest that PCI may have a useful role to play in the site specific activation of cytotoxic agents like gelonin, given at a dose level that has no effect in the absence of light.