Video capsule endoscopy (VCE) is a powerful diagnostic tool that has proven especially useful in imaging the small intestine. VCE technology offers greater magnification than traditional endoscopy while also providing excellent resolution. It is a clinically useful tool for detecting occult bleeding  and superficial lesions that are not radiographically observed [2, 3] ; it may also provide functional information as the capsule moves passively through the small intestine. 
The development of endoscopy enabled direct visualization of the esophagus, stomach, proximal small bowel, and colon.  However, even with these technological advances, certain limitations remained in the noninvasive diagnosis of gastrointestinal (GI) tract pathology. Much of the small bowel is not accessible with traditional endoscopy or even push endoscopy (which allows imaging up to 80-120 cm beyond the ligament of Treitz) but can be visualized with the capsule endoscope (see the image below). 
Capsule endoscopy is superior to radiographic techniques in the detection of mucosal disease and angiodysplasia.  Investigators have capitalized on the advantages of this approach, revealing an expanding list of clinical indications.
Technical advances in many areas (eg, optical design, light-emitting electrodes, and image sensors) were essential to the development of VCE, and the design was completed in 1997. In 1999, the first volunteer studies were performed, and high-quality images from volunteers were published in the literature shortly thereafter.  In 2001, VCE was approved by the US Food and Drug Administration (FDA) for use in patients in the United States, and by 2003, the capsule endoscope had already been used in more than 4000 patients. 
As surgeons gain experience with VCE technology, the list of indications for capsule endoscopy continues to grow. VCE has primarily been used as a diagnostic tool for detecting obscure GI bleeding,  but it has also aided in the diagnosis of inflammatory bowel disease (IBD) and celiac disease and helped in the detection of small-bowel neoplasia.
Obscure gastrointestinal bleeding
GI bleeding is obscure when it continues or recurs after upper and lower endoscopic examinations have found no source. Most obscure GI bleeding is due to lesions in the small intestine, a region that has traditionally been difficult to image adequately.  Before VCE, the standard procedure comprised a combination of diagnostic methods, including upper endoscopy, colonoscopy, and push enteroscopy, as well as enteroclysis, nuclear bleeding scans, angiography, and small-bowel follow-through studies.
VCE, which visualizes the entire mucosa of the small intestine, allows a more complete exploration. Capsule endoscopy may detect superficial lesions that barium studies miss. VCE has proved to be safe and effective and has a high diagnostic yield.  The diagnostic yield is greatest if the examination is performed within 1 month of the bleeding episode. 
Capsule endoscopy has been favorably compared with push endoscopy in patients with obscure GI bleeding. [13, 14, 15, 16] Leighton et al demonstrated the superior diagnostic yield of capsule enteroscopy for obscure GI bleeding as compared with that of push enteroscopy plus small-bowel follow-through study.  In this study, capsule endoscopy was found to be more sensitive, in that enteroscopy detected no cases that capsule endoscopy had missed.
In a comparison of the results of capsule endoscopy with those of intraoperative endoscopic findings, VCE was found to have a sensitivity of 95% and a specificity of 75%.  Diagnostic yield was slightly greater in patients with obscure or overt GI bleeding than in those with occult bleeding. Most detected lesions were telangiectasias (see the image below) and ulcerations. Normal results on capsule endoscopy are reassuring: 95.5% of patients with negative study results have no pathology on follow-up evaluation. [19, 20]
Neu et al found capsule endoscopy to be superior to standard tests for lesion detection and equivalent for guiding treatment decisions and enhancing outcome.  Capsule endoscopy can also detect lesions within reach of conventional methods (eg, colonoscopy and upper endoscopy). In one study, capsule endoscopy identified previously undetected sources of obscure GI bleeding in the colon and stomach.  Additional evaluation is required to determine whether capsule endoscopy should be a first-line test for obscure GI bleeding. 
Capsule endoscopy appears to have a clinically relevant positive impact on patient treatment and outcome, though the results are inconsistent. Mylonaki et al compared capsule endoscopy to push enteroscopy in 50 patients with obscure GI bleeding and found that capsule endoscopy not only detected more lesions but also led to changes in treatment in 71% of patients.  Viazis et al found that therapeutic interventions were possible in 82% of patients with positive capsule endoscopy findings and 35% of those with findings of uncertain significance. 
When 6-month outcomes were reviewed, further bleeding was uncommon (20%) among patients with a negative capsule study. Other studies that examined 6-month outcomes also suggest that those evaluated with capsule endoscopy for obscure GI bleeding undergo fewer subsequent diagnostic tests and require less transfusion. 
Whereas push endoscopy, for example, offers the capacity for biopsy and treatment (eg, argon plasma coagulation for angiodysplasia), capsule endoscopy does not allow immediate intervention. However, capsule endoscopy may be used to plan subsequent interventions.
In a study of outcomes in 33 patients observed for up to 20 months after undergoing capsule endoscopy for obscure GI bleeding, Maldonado et al found that the risk of rebleeding was significantly lower among those who received definitive treatment based on capsule endoscopy findings than among those with either negative or positive findings who received no intervention.  This finding led the authors to highlight the use of complementary treatment procedures.
Inflammatory bowel disease
Both of the major forms of IBD (ie, Crohn disease and ulcerative colitis) may involve the colon, but they may often be distinguished from each other on the basis of upper GI tract involvement. Proper diagnosis informs treatment decisions,  such as electing to pursue surgical rather than aggressive medical management for treatment-refractory individuals.
Crohn disease affects the small bowel in most individuals; in 30% of patients, the disease is limited to the terminal ileum.  The traditional approach to this diagnosis involves esophagogastroduodenoscopy, ileocolonoscopy, and radiography; unlike capsule endoscopy, these studies are limited in their ability to assess the jejunum and the proximal ileum. Barium studies are not as sensitive for the detection of early lesions, and traditional endoscopy is limited to the distal and proximal bowel.
When used to evaluate IBD, capsule endoscopy allows visualization of lesions (eg, small bowel erosions and ulcerations) in areas that other forms of endoscopy  or radiography [28, 29] would not visualize. Capsule endoscopy can localize and define the extent and activity of IBD.
Prospective studies have demonstrated that capsule endoscopy may be used to make the diagnosis of Crohn disease (see the image below). [30, 31] In patients believed to have Crohn disease with small-bowel involvement, capsule endoscopy may provide a higher diagnostic yield than enteroclysis. 
In a small study of 21 patients with symptoms consistent with IBD, typical findings on upper and lower endoscopy, and typical barium radiology findings, capsule endoscopy was able to detect findings consistent with IBD in 43% of patients. 
A meta-analysis comparing the diagnostic yield of capsule endoscopy with that of other modalities (eg, barium studies, colonoscopy with ileoscopy, computed tomography [CT] enterography or enteroclysis, and small-bowel magnetic resonance imaging [MRI]) found capsule endoscopy to be superior in the diagnosis of a recurrence in nonstricturing small-bowel Crohn disease. 
For the initial diagnosis of persons with suspected Crohn disease, a trend toward improved yield was observed, although the difference was not statistically significant.  Additional studies are required to define the role of capsule endoscopy in the evaluation of suspected Crohn disease.
Because the established diagnostic criteria for IBD rely on histologic examination, the macroscopic abnormalities visible on capsule endoscopy may not be specific enough for definitive diagnosis. However, many small-bowel lesions visible on capsule endoscopy are in areas that tools with biopsy capability cannot visualize. 
Small-bowel polyps and neoplasia
Small-bowel neoplasia occurs in 75% of patients with Peutz-Jeghers syndrome (PJS) and 90% of patients with familial adenomatous polyposis (FAP).  In patients with FAP, therapeutic interventions in jejunal and ileal polyps remain undefined, perhaps because of the low incidence of nonduodenal small-bowel cancer. In patients with PJS, the risks of small-bowel cancer and obstruction are known, and screening may help avoid emergency surgery or cancer.
Patients with PJS may require operative intervention for small-bowel obstruction or intussusception. Capsule endoscopy is superior to barium contrast study in detecting small-bowel polyps in patients with hereditary polyposis syndromes.  Capsule endoscopy may help localize large polyps, which, in turn, may be removed by means of enteroscopy. 
Small-bowel neoplasia has been difficult to detect with standard methods but has been detected with capsule endoscopy. In a retrospective chart review of 562 patients undergoing capsule endoscopy for various indications, Cobrin et al found that 8.9% were given a diagnosis of small-bowel tumor (eg, adenocarcinoma, carcinoid, GI stromal tumor, lymphomas, inflammatory polyp, lymphangioma, lymphangioectasia, hemangioma, hamartoma, and tubular adenoma) and 48% of the tumors were malignant. 
Several of the patients in this study had previously undergone push enteroscopy with negative results.  The improved diagnostic yield of a noninvasive method may facilitate early detection of small-bowel cancers, which, in turn, may affect outcome.
In a review of the charts of 667 patients undergoing capsule endoscopy for various indications, Toth et al found that 7.7% of patients undergoing evaluation for obscure GI bleeding and 2.2% of patients undergoing the examination for other reasons were given a diagnosis of small-bowel neoplasm on the basis of capsule endoscopy findings.  Clinically significant polyps, once detected, can prompt operative intervention for patients with PJS and FAP. 
Histologic examination of duodenal tissue obtained during upper GI endoscopy is the current criterion standard for the diagnosis of celiac disease. Capsule endoscopy has been considered an alternative diagnostic tool because the magnification it provides is sufficient for imaging the villi and detecting villous atrophy (see the image below). In a study of 43 patients with serology and symptoms suggestive of celiac disease, Rondonotti et al used upper endoscopy–acquired biopsy results to evaluate capsule endoscopy as a diagnostic tool for celiac disease. 
In another study, experienced gastroenterologists reviewed capsule endoscopy examinations for findings such as flattened mucosa, mosaic appearance, and scalloped duodenal folds, then compared these findings with the biopsy results; capsule endoscopy had a sensitivity of 87.5% and a specificity of 90.9%. 
On the basis of a preliminary study that included 17 patients, De Vitis et al suggested that capsule endoscopy complements traditional endoscopy in the evaluation of celiac disease by providing data about disease complications (eg, erosive jejunitis) and by confirming the degree of mucosal damage. 
Contraindications for VCE include the following:
Careful consideration is warranted in patients with diabetes or a history of major abdominal surgery.  Small studies have investigated the safety of capsule endoscopy in patients with cardiac pacemakers and implantable cardiac defibrillators. 
Patients should not undergo MRI until the capsule is excreted. 
The safety and efficacy of capsule endoscopy in the pediatric population remain to be firmly established, though the literature includes a few positive case reports. [7, 43, 44] The Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Spanish Society for Digestive Diseases have developed a guideline for the use of wireless capsule endoscopy in children and adolescents.  A study by Urgesi et al found capsule endoscopy to be appropriate in patients older than 70 years. 
Technical problems and limitations
Outcomes for specific indications are discussed above (see Indications). More general observations were noted by Rondonotti et al, who retrospectively analyzed 733 capsule endoscopy examinations performed at referral centers and found that the procedure was associated with few technical problems, most of which occurred while the center was gaining experience with the technique. 
Problems encountered included gaps in the recording (4% in this analysis) and short battery life (2.34%).  Clinical limitations included the inability to swallow the capsule in 1.5% of patients and failure of the capsule to progress to the ileocecal valve during the recording interval in 14.97%, most often because of delayed gastric emptying.
In two large reviews of capsule endoscopy performed for a variety of indications, [47, 12] the procedure was found to be safe and reliable for locating GI tract abnormalities, especially in the small bowel, an area where other imaging modalities were unsuccessful.
The cost-effectiveness of capsule endoscopy and its impact on outcome remain to be determined.
A follow-up study in France assessed 92 patients who underwent capsule endoscopy for a variety of indications and found that at 1 year, the positive and negative predictive values were 100% and 94%, respectively.  The group concluded that capsule endoscopy may become the first diagnostic tool used after negative upper and lower endoscopy studies. In addition, with such a high negative predictive value, a negative capsule study should generally be sufficient to guide the work away from a search for small-bowel pathology.
In Japan  and Italy,  studies of capsule endoscopy for obscure GI bleeding supported capsule endoscopy as a cost-effective tool. A promising initial study that compared capsule endoscopy with push enteroscopy for obscure GI bleeding found capsule endoscopy to be a more efficient first-line test in terms of diagnostic capability and negative predictive value. 
In obscure GI bleeding, push enteroscopy offers the capability of biopsy and endotherapy in those areas that it can image effectively. This relative benefit must be balanced against the finding that in patients with previously negative evaluations for GI bleeding, capsule endoscopy is more effective in finding abnormalities but does not offer immediate intervention. In irritable bowel disease, capsule endoscopy provides information about macroscopic lesions but does not allow histologic examination of the tissue.
Capsule endoscopy provides more information than traditional barium studies but may carry a risk of capsule retention in patients with IBD and stricturing disease.  Future studies are also likely to define the use of capsule endoscopy in children.  Capsule endoscopy may also play a role in the evaluation of esophageal disorders (eg, Barrett esophagus), [52, 53] as an alternative to upper endoscopy for upper GI bleeding, and in the evaluation of portal hypertension and esophageal varices.