Future innovative therapies to treat upper gastrointestinal bleeding.

The age of patients admitted to hospital for gastrointestinal bleeding will probably continue to rise, pushing the mortality rate upward, and the use of arthritic and blood thinning drugs will increase the incidence of gastrointestinal bleeding, especially in elderly patients. A slow decrease may be seen in the incidence of Helicobacter-induced ulceration and consequent bleeding in the west. New vaccine development has the best chance of reducing upper gastrointestinal bleeding worldwide, especially that caused by viral infections. Innovations in mechanical and compressive thermal hemostasis offer the best prospects for improvement in outcome from flexible therapeutic endoscopy.

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.).

At a watershed? Technical developments in wireless capsule endoscopy.

This article reviews some of the technical developments that allowed the introduction of the wireless capsule 10 years ago into human usage. Technical advances and commercial competition have substantially improved the performance of clinical capsule endoscopy, especially in optical quality. Optical issues including the airless environment, depth of focus, dome reflection, the development of white light light-emitting diodes, exposure length and the advent of adaptive illumination are discussed. The competition between charge coupled devices and complementary metal oxide silicone technologies for imaging, lens improvements and the requirements for different frame rates and their associated power management strategies and battery type choices and the introduction of field enhancement methods into commercial capsule technology are considered. Capsule technology stands at a watershed. It is mainly confined to diagnostic small intestinal imaging. It might overtake other forms of conventional diagnostic endoscopy, especially colonoscopy but also gastroscopy and esophagoscopy but has to improve both technically and compete in price. It might break out of its optical diagnostic confinement and become a therapeutic modality. To make this leap there have to be several technical advances especially in biopsy, command, micromechanical internal movements, remote controlled manipulation and changes in power management, which may include external power transmission.

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.

Remote magnetic manipulation of a wireless capsule endoscope in the esophagus and stomach of humans (with videos).

BACKGROUND: Remote manipulation of wireless capsule endoscopes might improve diagnostic accuracy and facilitate therapy. OBJECTIVE: To test a new capsule-manipulation system. SETTING: University hospital. DESIGN AND INTERVENTIONS: A first-in-human study tested a new magnetic maneuverable wireless capsule in a volunteer. A wireless capsule endoscope was modified to include neodymium-iron-boron magnets. The capsule's magnetic switch was replaced with a thermal one and turned on by placing it in hot water. One imager was removed from the PillCam colon-based capsule, and the available space was used to house the magnets. A handheld external magnet was used to manipulate this capsule in the esophagus and stomach. The capsule was initiated by placing it in a microg of hot water. The capsule was swallowed and observed in the esophagus and stomach by using a gastroscope. Capsule images were viewed on a real-time viewer. MAIN OUTCOME MEASUREMENTS: The capsule was manipulated in the esophagus for 10 minutes. It was easy to make the capsule turn somersaults and to angulate at the cardioesophageal junction. In the stomach, it was easy to move the capsule back from the pylorus to the cardioesophageal junction and hold/spin the capsule at any position in the stomach. The capsule in the esophagus and stomach did not cause discomfort. LIMITATIONS: Magnetic force varies with the fourth power of distance. CONCLUSIONS: This study suggests that remote manipulation of a capsule in the esophagus and stomach of a human is feasible and might enhance diagnostic endoscopy as well as enable therapeutic wireless capsule endoscopy.

Development and testing of a tethered, independent camera for NOTES and single-site laparoscopic procedures.

BACKGROUND: "Tunnel vision" associated with endoscopes used in NOTES and laparoscopes used in laparoendoscopic single-site surgery (LESS) procedures present the surgeon with a disorienting view of familiar surroundings. Given the in-line arrangement of the devices, it is difficult to achieve adequate triangulation, a critical component of successful surgical technique. A potentially more useful vantage point would be from above, looking down at the surgical field, i.e., "stadium view." The purpose of this study was to develop stadium-view camera prototypes for evaluation. METHODS: Cylindrical (15 mm diameter, 30 mm length) imagers were built using white light LEDs for illumination and a near-VGA resolution CMOS camera. These prototypes were delivered to the abdominal cavity through an overtube (Steerable Flex Trocar (SFT)); the electronic tether for power and video signal was pulled through the abdominal wall using a 2-mm rigid grasper. The prototypes were attracted to the abdominal wall magnetically. Clinicians performed the procedures in IACUC/Home Office-approved porcine labs. RESULTS: Introduction of the device into the peritoneal cavity and magnetic coupling to the abdominal wall were straightforward. Illumination was adequate to provide reasonable imagery of nearby abdominal organs. Bowel was successfully sutured laparoscopically under visualization provided by the prototype. All points on the abdominal wall could be reached via the magnetic control, and the camera could be successfully aimed through abdominal palpation. Retrieval was uncomplicated. CONCLUSIONS: The prototypes provide the clinician a point of view similar to that of a traditional laparoscope, although the image quality needs improvement. The stadium view helps to overcome limitations associated with in-line visualization and working tools. Use of such a camera in NOTES or LESS could enable reduction of the number/size of ancillary trocars, reduce the size of the LESS port, and/or increase the number of working devices that can be deployed.

Status of endoscopes and instruments used during NOTES.

Natural orifice translumenal endoscopic surgery (NOTES) requires an intentional perforation of a hollow lumen to pass an endoscope into an otherwise inaccessible body cavity with diagnostic or therapeutic intent. The limitations of current flexible instruments for this purpose are outlined, including the unsuitability for NOTES of current flexible needle knives, guidewires, balloons, overtubes, grasping forceps, and scissors. The development of novel suturing instruments, trocars, articulating instruments, flexible bipolar forceps, flexible clips, magnetic devices, and staplers as well as the advent of manual mechanical manipulators for flexible accessories is outlined. New instrument solutions for endosurgery are described, such as articulating flexible accessories for gastroscopes, novel "platforms" that can be rigidized, and unconventional scope arrangements. Debatably, the greatest current benefit of NOTES is that it may lead to further development of better instrumentation for endosurgery.

Development and validation of a new generation of flexible endoscope for NOTES.

BACKGROUND: The concept of intraperitoneal flexible endoscopy has created much interest and investigation. Both gastroenterologists with a surgical leaning and surgeons with advanced endoscopy interests are researching the feasibility of this new approach. Current flexible scopes and instruments are extremely limited for use in natural orifice transluminal endoscopic surgery (NOTES). We describe the development of an endoscopic system specifically designed for endoluminal and NOTES procedures and demonstrates benefits and efficacy in benchtop and cadaver models. TECHNIQUE: In conjunction with industry, an 18-mm 4-channel rigidizing access device was designed. Measurements of the strength (torsional and lifting) of standard endoscopes and the new scope were made. The new device and instruments are used in 8 cadavers to document its feasibility in a variety of specific tasks: endoluminal plication, upper abdomen and lower abdomen visualization, bowel manipulation, solid organ retraction, cholecystectomy, and enterotomy closure. RESULTS: Benchtop comparison between a standard scope and the new scope showed equal maneuverability but the newer scope had greater force delivery at the tip (0.042 vs 1.96 lb, P < .001) and greater instrument application force (0.09 vs 0.23 lb, P < .002). Introduction of the scope was possible in all cadavers but difficult in cadavers <60 kg. Intragastric manipulation was feasible and exiting the stomach was possible although it required a 2-cm gastrotomy. The scope system was maneuverable in both lower quadrants without difficulty. The upper abdomen was viewable, with variable success in steering the scope between left and right quadrants. The entire gastrointestinal tract was able to be visualized in most cadavers. The scope generated sufficient force to lift and manipulate intraabdominal structures. Cholecystectomy was successful in 5 of 5 attempts. CONCLUSION: A new flexible access endoscope with 4 large access channels showed utility in a cadaver model-satisfying some of the requirements for performance of NOTES procedures.

Initial experimental evaluation of wireless capsule endoscopes in the bladder: implications for capsule cystoscopy.

BACKGROUND: Cystoscopy remains one of the most important diagnostic procedures for the lower urinary tract. Wireless capsule endoscopy was introduced in the 1990s but use to date is limited to gastroenterology. OBJECTIVE: We evaluated the feasibility in the pig model of using wireless capsule endoscopes (WCEs) for cystoscopy. DESIGN, SETTING, AND PARTICIPANTS: Experimental evaluation of capsule cystoscopy was performed in a 50-kg farm pig. The capsule was deployed into the bladder through a custom access sheath. Images were continuously transmitted at a rate of four frames per second to a laptop computer and processed using proprietary software. Manipulation of the WCE within the bladder was performed using a set protocol. The animal was then euthanized and gross inspection was performed. MEASUREMENTS: We measured the ability to deploy and manipulate the capsule within the bladder. Feasibility of capturing and retrieving images in real time was also assessed. RESULTS AND LIMITATIONS: The WCE was efficiently deployed and manipulated within the bladder passively and with the use of external magnets. The entire bladder mucosa was visualized. Real-time image transmission and capture were successful. No complications were seen during capsule cystoscopy. Minor urethral bleeding was observed after the experiment, likely related to placement of the access sheath required for deployment of the WCE. Limitations are that the evaluation of WCE was performed in the pig model, in only one female animal, using a nonsurvival approach. Furthermore, the study was not designed to differentiate normal from abnormal mucosal findings and focused solely on inspection of the bladder. CONCLUSIONS: This report suggests that cystoscopy with a WCE is feasible. With this device, all aspects of the bladder mucosa could be visualized, and ongoing technologic and procedural developments are warranted for this new approach.

Endoscopic closure of transmural bladder wall perforations.

BACKGROUND: Traditionally, intraperitoneal bladder perforations caused by trauma or iatrogenic interventions have been treated by open or laparoscopic surgery. Additionally, transvesical access to the peritoneal cavity has been reported to be feasible and useful for natural orifice translumenal endoscopic surgery (NOTES) but would be enhanced by a reliable method of closing the vesicotomy. OBJECTIVE: To assess the feasibility and safety of an endoscopic closure method for vesical perforations using a flexible, small-diameter endoscopic suturing kit in a survival porcine model. DESIGN, SETTING, AND PARTICIPANTS: This pilot study was performed at the University of Minho, Braga, Portugal, using six anesthetized female pigs. INTERVENTIONS: Closure of a full-thickness longitudinal incision in the bladder dome (up to 10 mm in four animals and up to 20 mm in two animals) with the endoscopic suturing kit using one to three absorbable stitches. MEASUREMENTS: The acute quality of sealing was immediately tested by distending the bladder with methylene-blue dye under laparoscopic control (in two animals). Without a bladder catheter, the animals were monitored daily for 2 wk, and a necropsy examination was performed to check for the signs of peritonitis, wound dehiscence, and quality of healing. RESULTS AND LIMITATIONS: Endoscopic closure of bladder perforation was carried out easily and quickly in all animals. The laparoscopic view revealed no acute leak of methylene-blue dye after distension of the bladder. After recovery from anaesthesia, the pigs began to void normally, and no adverse event occurred. Postmortem examination revealed complete healing of vesical incision with no signs of infection or adhesions in the peritoneal cavity. No limitations have yet been studied clinically. CONCLUSIONS: This study demonstrates the feasibility and the safety of endoscopic closure of vesical perforations with an endoscopic suturing kit in a survival porcine model. This study provides support for further studies using endoscopic closure of the bladder which may lead to a new era in management of bladder rupture and adoption of the transvesical port in NOTES procedures.

The future of wireless capsule endoscopy.

We outline probable and possible developments with wireless capsule endoscopy. It seems likely that capsule endoscopy will become increasingly effective in diagnostic gastrointestinal endoscopy. This will be attractive to patients especially for cancer or varices detection because capsule endoscopy is painless and is likely to have a higher take up rate compared to conventional colonoscopy and gastroscopy. Double imager capsules with increased frame rates have been used to image the esophagus for Barrett's and esophageal varices. The image quality is not bad but needs to be improved if it is to become a realistic substitute for flexible upper and lower gastrointestinal endoscopy. An increase in the frame rate, angle of view, depth of field, image numbers, duration of the procedure and improvements in illumination seem likely. Colonic, esophageal and gastric capsules will improve in quality, eroding the supremacy of flexible endoscopy, and become embedded into screening programs. Therapeutic capsules will emerge with brushing, cytology, fluid aspiration, biopsy and drug delivery capabilities. Electrocautery may also become possible. Diagnostic capsules will integrate physiological measurements with imaging and optical biopsy, and immunologic cancer recognition. Remote control movement will improve with the use of magnets and/or electrostimulation and perhaps electromechanical methods. External wireless commands will influence capsule diagnosis and therapy and will increasingly entail the use of real-time imaging. However, it should be noted that speculations about the future of technology in any detail are almost always wrong.

Endoscopic closure of colon perforation compared to surgery in a porcine model: a randomized controlled trial (with videos).

BACKGROUND: Endoscopic closure of inadvertent or intentional colon perforations might be valuable if comparable to surgical closure. OBJECTIVE: The aim of this study was to compare endoscopic closure of a 4-cm colon perforation in a porcine model with surgical closure in a multicenter study. SETTING: University hospitals in the United States and Europe. DESIGN AND INTERVENTIONS: After creating a 4-cm linear colon perforation, the animals were randomized to either endoscopic or surgical closure. The total procedure time from the beginning of perforation to the completion of procedure was measured. The animals were euthanized after 2 weeks to evaluate healing, unless there was a complication. RESULTS: Fifty-four animals were randomized to either surgical or endoscopic closure of colon perforation. Eight animals developed complications, and 7 of these were euthanized before 2 weeks. Twenty-three animals in each group survived for 2 weeks. Surgical closure of the perforation was successful in all animals in that group, and endoscopic closure was successful in 25 of the 27 animals. The median procedure time was shorter in the surgery group compared to the endoscopy group (35 vs 44 minutes, P = .016). Peritonitis, local adhesions, and leak test results were comparable in both groups. Distant adhesions were less frequent in the endoscopic closure group (26.1% vs 56.5%, P = .03). Five of the 186 T-tags (2.7%) were noted in the adjacent viscera. LIMITATION: This porcine study does not mimic clean colon perforation in humans; it mimics dirty colon perforation in humans. CONCLUSIONS: Endoscopic closure of a 4-cm colon perforation was comparable to surgery, and this technique can be potentially used for closure of intentional or inadvertent colon perforations.

Nephrectomy and natural orifice translumenal endoscopy (NOTES): transvaginal, transgastric, transrectal, and transvesical approaches.

This paper outlines recent developments in the field of natural orifice translumenal endosurgery (NOTES) in urology and nephrectomy from the perspective of a flexible endoscopist. The history of transvaginal extraction of kidney specimens using rigid laparoscopic instruments and early studies of transvaginal nephrectomy as a precursor of NOTES are reviewed. Transgastric approaches to nephrectomy using flexible instruments and transvesical hybrid approaches to nephrectomy and other intra-abdominal procedures including cholecystectomy and transvesical lung biopsy are outlined, as are other experimental approaches including transrectal kidney removal. The paper reviews the rationale for a NOTES approach to abdominal surgery and discusses recent human studies. The limitations of NOTES and need for better instrumentation and more studies are stressed.

NOTES and anastomosis.

The history and development for forming anastomoses using natural orifice translumenal endoscopic surgery (NOTES) techniques is described. Sutured gastrojejunostomy, enteroenteral anastomosis, and ileocolonic anastomoses using rigid and circular staplers passed through the rectum and vaginal wall using a transgastric supervising endoscope using a natural orifice translumenal endoscopic surgery hybrid approach. The staplers for this type of approach have to change. They need to be longer, more flexible, and able to change shape (eg, becoming smaller for introduction and then expanding in the peritoneal cavity). Different methods of introduction over guidewires or in combination with flexible gastroscopes are also needed. There is still a requirement for more ingenuity, persistence, and research if the goal of safer effective formation of anastomoses by less invasive means is to be realized.

Early clinical experience with a new flexible endoscopic suturing method for natural orifice transluminal endoscopic surgery and intraluminal endosurgery (with videos).

BACKGROUND: To perform advanced endoscopic treatments, one has to be able to close defects and perforations. Many devices have been constructed to perform endoscopic suturing, but all are rather complicated, expensive, and difficult to use. OBJECTIVE: To develop and use a new simple stitching technique at intraluminal flexible endoscopy. DESIGN: A flexible 19-gauge needle, loaded with a metal tag attached to a 3-0 polypropylene thread is passed down the working channel of a conventional endoscope. Two tags are placed into the stomach or the intestinal wall, 1 on each side of the defect. The threads are then locked together and cut. Precise stitch positioning is possible. Multiple stitches can be placed quickly, without removal of the endoscope. SETTING: Surgical department at Sahlgrenska University Hospital in Göteborg, Sweden. PATIENTS: Three patients in whom other conventional treatments had failed. INTERVENTIONS: Initially, survival studies in pigs were performed, and full-thickness resections, pyloroplasty, and gastrojejunostomies could be completed. The technique was subsequently used in patients when surgery was not feasible and when other endoscopic interventions had failed. MAIN OUTCOME MEASUREMENTS: Clinical evaluation; successful sealing of defects, leaks, or a bleeding vessel. RESULTS: We present 3 human cases and describe endoluminal closure of a perforated duodenal ulcer, a leaking gastroenteroanastomosis after gastroplasty, and successful treatment of upper-GI bleeding by oversewing a bleeding vessel. CONCLUSIONS: This stitching technique is easy to use and makes endoscopic suturing possible for closure of perforations and tissue approximation almost anywhere in the GI tract that can be reached by a flexible endoscope.

Endoscopic suturing: now and incoming.

There is a particular need for inexpensive, simple multipurpose suturing methods that can be used for most applications. Such devices are in advanced stages of development and early clinical use. Complex procedure-specific devices that fix large-volume procedures such as reflux or obesity may well be needed but will need to prove their value in clinical studies.

Measurements of intraperitoneal pressure and the development of a feedback control valve for regulating pressure during flexible transgastric surgery (NOTES).

BACKGROUND: High intraabdominal pressures during laparoscopy (greater than 15 mm Hg) are dangerous. Pressures developed during translumenal endosurgery when using flexible endoscopes without feed-back regulation are unknown. OBJECTIVE: To measure and control intraabdominal pressures during transgastric endosurgery. DESIGN: In a blinded study, intraabdominal pressures during unregulated transgastric cholecystectomy and tubal ligation were measured by using Veress needles in 5 pigs (group 1). The accessory channel valve of a double-channel gastroscope was modified to allow measurement and control of intraabdominal pressures with a laparoscopic insufflator. This was tested prospectively in another blinded study in 5 pigs (group 2) that underwent identical procedures to those in group 1, with independent Veress needle pressure measurements. SETTING: This ethically approved study was performed in an experimental surgical operating theater. INTERVENTIONS: Transgastric cholecystectomy (n=4) and tubal resection (n=6). MAIN OUTCOME MEASURES: Intraabdominal pressure measurements during transgastric endosurgery, with and without feed-back control. RESULTS: The mean (standard deviation) number of pressure measurements per procedure greater than 20 mm Hg was 11+/-1.41 in group 1 and 0+/-0 in group 2 (P<.05). Most episodes of high pressure were undetected by the endoscopist, who was blinded to the pressure measurements. CONCLUSIONS: Unacceptably high intraabdominal pressures were common during translumenal endosurgical procedures. Feedback pressure regulation through a modified valve prevented overinflation.

Endoscopic pyloroplasty with full-thickness transgastric and transduodenal myotomy with sutured closure.

BACKGROUND: Pyloroplasty with myotomy and sutured closure is a surgical treatment for gastric outlet obstruction. It has not been previously performed at flexible endoscopy. OBJECTIVE: To develop and test a method for performing a sutured pyloroplasty at flexible endoscopy. DESIGN: A Heinicke-Miculicz pyloroplasty was performed, forming a linear myotomy through the pylorus from the gastric side into the duodenal bulb. This was subsequently sutured transversely to increase the opening. The operation was performed in 3 nonsurvival studies in pigs. The safety and the efficacy was then studied in 7 animals followed for up to 4 weeks after the procedure. SETTING: The studies were performed in experimental surgical units in Gothenburg, Sweden, and London, UK. INTERVENTIONS: A linear needle-knife incision was made through the pylorus; full-thickness sutures, by using a new T-tag and polypropylene thread suturing system through a flexible gastroscope, were placed to close the incision transversely. In 2 pigs, the prepyloric bulge was excised before the pyloroplasty. RESULTS: Pyloroplasty was readily accomplished at flexible endoscopy in the 3 nonsurvival studies. Six of 7 pigs that survived in this study for periods of 7 to 28 days, recovered well, without complications. One pig (with bulge removal) developed gastric retention. The pyloric opening was increased; it was then easy to enter the duodenum at follow-up endoscopy. LIMITATIONS: This method has yet to be studied clinically. CONCLUSIONS: Pyloroplasty with full-thickness pyloromyotomy and transverse closure of a linear myotomy was accomplished by using a simple flexible endosurgical technique to test a new flexible suturing system.