Aetna considers capsule endoscopy medically necessary for the following indications:

1. For investigating suspected small intestinal bleeding in persons with objective evidence of recurrent, obscure gastrointestinal bleeding (e.g., iron-deficiency anemia, positive fecal occult blood test, or visible bleeding) who have had upper and lower gastrointestinal endoscopies within the past 12 months (esophagogastroduodenoscopy (EGD) and colonoscopy) that have failed to identify a bleeding source; or
2. For initial diagnosis in persons with suspected Crohn's disease (abdominal pain or diarrhea plus one or more signs of inflammation (fever, elevated white blood cell count, elevated erythrocyte sedimentation rate, or bleeding)) without evidence of disease on conventional diagnostic tests, including small-bowel follow-through or abdominal CT scan and upper and lower endoscopy (esophagogastroduodenoscopy (EGD) and colonoscopy); or  
3. For evaluation of locoregional carcinoid tumors of the small bowel in persons with carcinoid syndrome; or
4. For evaluation of persons with celiac disease with a positive serology and negative biopsy; or
5. For screening or surveillance of esophageal varices.

Capsule endoscopy is contraindicated and considered experimental and investigational in persons with known or suspected gastrointestinal obstruction, strictures, or fistulae.

Aetna considers capsule endoscopy of the intestine experimental and investigational for evaluating abdominal pain unless one or more of the above-listed criteria are met.

Aetna considers capsule endoscopy experimental and investigational for all other indications, including use as a screening test, use as an initial test in diagnosing gastrointestinal bleeding; use in confirming pathology identified by other diagnostic means, for follow-up of persons with known small bowel disease, use in investigating duodenal lymphocytosis, suspected irritable bowel syndrome, recurrent intussusception, celiac sprue, small bowel neoplasm, or intestinal polyposis syndrome, and for evaluation of diseases involving the esophagus other than esophageal varices, and for evaluation of the colon.

Aetna considers the Agile patency capsule experimental and investigational for evaluating patency of the gastrointestinal tract before wireless capsule endoscopy, and for all other indications.

According to guidelines from the American Gastroenterological Association (2001), the current standard for diagnosing the source of small intestinal bleeding is push enteroscopy, in which a four-foot long tube outfitted with a small video camera is inserted down the esophagus, through the stomach and into the first third of the small intestine. In many cases, a definitive diagnosis cannot be made because the imaging tools cannot reach far enough into the digestive tract to find the problem. Radiologic examination of the small bowel with barium (enteroclysis) may be uncomfortable, time-consuming, and is incapable of detecting completely flat lesions of the small intestine (e.g., arteriovenous malformations).

In August 2001, the U. S. Food and Drug Administration (FDA) cleared for marketing a swallowable capsule containing a small camera that snaps pictures twice a second as it passes through the small intestine. The FDA classified the capsule, called the Given Diagnostic Imaging System (Given Imaging Ltd., Yoqneam, Israel), as a Class II device that is subject only to general regulatory controls. The capsule, marketed as the PillCam SB (previously marketed as M2A™), has a clear end that allows the camera to view the lining of the small intestine. In addition to the camera, the wireless capsule, about the size of a large vitamin pill, contains a lighting system and a transmitter that will send images from inside the intestine to video monitors, allowing doctors to detect sources of bleeding in the small intestine. FDA cleared the device for use along with, not as a replacement for, other endoscopic and radiological evaluations of the small intestine. The capsule was not studied in the large intestine.

When swallowed, the device travels down the digestive tract at about the same speed as food, propelled by peristalsis, and takes two to three hours to pass through. Once the device reaches the colon, things slow down, and the disposable device is eliminated like any solid waste within a few days.

The downside to this technology is that the images may not match fiber-optic endoscopes for detail, and concerns have been raised that the camera's view may be obscured by bubbly saliva or green bile. The capsule cannot be stopped or steered to collect close-up details of the small intestine's millions of interior wrinkles where ailments often occur. Nor is it fitted with surgical tools like a conventional endoscope to take biopsies or treat bleeding lesions or remove polyps. If a lesion requiring invasive therapy is found on capsule endoscopy, then the patient will need to undergo surgery with intraoperative endoscopy. In addition, if an abnormality is seen on capsule endoscopy, there is no good way to define its location within the small intestine. Fleischer (2002) has noted that, with capsule endoscopy, “the pylorus is usually seen, and in many patients the ileocecal valve can be demonstrated, but apart from a rough estimate linked to 'time beyond the pylorus' or 'time in front of the ileocecal valve', specific localization is not possible.”

By contrast, push enteroscopy has the advantages of being able to perform biopsies and offer therapy. If capsule endoscopy is performed without a prior push enteroscopy, a push enteroscopy will still need to be performed in most cases since a negative capsule endoscopy may not exclude a lesion, and a lesion observed on capsule examination may be within reach of the enteroscope (Faigel & Fennerty, 2002).

In a study submitted to the FDA, the Given Imaging Diagnostic System detected physical abnormalities in 12 of 20 patients with suspected small intestinal disorders, while push enteroscopy detected physical abnormalities in 7 of 20 patients. All patients included in the trial had previously undergone gastrointestinal endoscopies and radiological procedures to identify the source of their small intestinal disorders, without a conclusive diagnosis. In total, 14 lesions were detected in 13 of the 20 patients participating in the clinical trials using either the Given Imaging Diagnostic System, push enteroscopy or surgical techniques. The Given Imaging Diagnostic System detected 12 of the 14 lesions, while push enteroscopy detected 7 of 14. The investigators also noted that the Given system was able to identify sources of bleeding in five cases that were beyond the reach of the traditional enteroscope.

Costamagna, et al. (2002) compared the performance of capsule endoscopy to upper gastrointestinal barium radiography series with small bowel follow through in 20 patients, including 13 patients with obscure gastrointestinal bleeding, 3 patients with suspected Crohn's disease, 1 patient with suspected sarcoma recurrence, 1 patient with diarrhea, 1 patient with familial adenomatous polyposis, and 1 patient with small intestine polyposis. The rates of a “diagnostic” test were higher for capsule endoscopy (45 percent) than for barium examination (27 percent), although no test was performed to determine whether this difference was statistically significant. Among the subset of 13 patients with obscure gastrointestinal bleeding, the rates of a diagnostic test were statistically significantly higher for capsule endoscopy (30 percent) than for the barium study (5 percent); however, the study does not describe how this statistical analysis was performed.

This study has been criticized on several grounds (see, e.g., Faigel & Fennerty, 2002). First, the small heterogenous population included in this study makes it difficult to discern the role of this new technology in clinical practice. Second, the study does not evaluate all relevant competing technologies; specifically, the study does not examine how capsule endoscopy performs in comparison to enteroclysis or push enteroscopy; the latter may have been a more appropriate endoscopic standard for comparison. Third, the study chose to report on “diagnostic yield” because no gold standard study was performed; diagnostic yield cannot differentiate true from false positives or true from false negatives. Two studies reported higher diagnostic yields with capsule endoscopy than push enteroscopy in small groups of patients with chronic gastrointestinal bleeding. Lewis and Swain (2002) reported on the results of a pilot study of capsule endoscopy and push enteroscopy in 21 adult patients with obscure gastrointestinal bleeding whose source was not uncovered with EGD, colonoscopy or small bowel follow through. Capsule endoscopy was able to identify a bleeding source in 11 patients (55%), whereas push enteroscopy was able to identify a bleeding source in 6 patients (30%) (p = 0.0625). In Germany, Ell, et al. (2002) reported on a comparison of capsule endoscopy to push enteroscopy in 32 patients with chronic gastrointestinal bleeding. Push enteroscopy revealed definite bleeding sites in nine patients (28%), including angiodysplasia in seven patients, small intestine cancer in one patient, and lymphoma in one patient. Capsule endoscopy detected definite bleeding sites in 21 patients (66%), including angiodysplasia in 17 patients, malignant stenoses in two patients, and inflammatory small-intestine disease in two patients. Questionable bleeding sources were seen on push enteroscopy in three additional patients (9%) and using capsule endoscopy in an additional seven patients (22%).

Much of the clinical evidence on capsule endoscopy has been presented in the form of abstracts rather than as peer-reviewed published clinical studies. As no study has compared capsule endoscopy to surgical enteroscopy or some other reliable external criterion (i.e., gold standard), the sensitivity, specificity, and predictive values of capsule endoscopy are unknown. In addition, no study has reported on the effect of capsule endoscopy on resolution of bleeding or other relevant clinical outcomes.

In the acute setting, capsule endoscopy is not a substitute for tagged red cell scintigraphy or angiography, because capsule endoscopy takes 8 hours to complete with the results generally not available until the following day.

The BlueCross BlueShield Technology Evaluation Center (2003) evaluated the evidence supporting the use of capsule endoscopy for diseases of the small intestine other than obscure gastrointestinal bleeding. The assessment identified no randomized controlled clinical studies of capsule endoscopy for these indications. The assessment identified three published studies (Fireman, et al., 2003; Herrerias, et al., 2003; Eliakim, et al., 2003), involving a total of 58 patients, that prospectively examined the use of capsule endoscopy for initial diagnosis of suspected Crohn's disease when all conventional diagnostic tests, including small-bowel follow-through, have failed to reveal bowel lesions suggestive of Crohn's disease. An additional 41 patients were included in 2 abstract reports and case reports (Sant'anna, et al., 2003; Bloom, et al, 2003; Costamanga, et al., 2003; Chong, et al, 2003; Liangpunsakul, et al., 2003). The assessment concluded that “[t]hese studies provide consistent evidence that wireless capsule endoscopy may demonstrate small-bowel lesions suggestive of Crohn's disease in a significant proportion of patients ranging from 43 to 71% when all other conventional tests have been negative. Furthermore, patients in these studies diagnosed with Crohn's disease by wireless capsule endoscopy were reported to improve after treatment for Crohn's disease, which represents an improvement in health outcomes.”

The assessment did not find sufficient evidence to support the use of capsule endoscopy for other indications, including initial diagnosis of irritable bowel syndrome, celiac sprue, small bowel neoplasm, or intestinal polyposis syndrome, or follow up of persons with known small bowel diseases. The assessment identified one published study, involving 20 patients, that examined the diagnostic yield of capsule endoscopy in persons with suspected irritable bowel syndrome, but none of the subjects had significant findings on capsule endoscopy (Bardan, 2003). The assessment found that the evidence for all remaining indications was limited to abstracts and case reports.

An assessment by the National Institute for Clinical Excellence (2004) found adequate evidence to support the use of capsule endoscopy, but that “[c]linicians should consider the use of other investigations prior to wireless capsule endoscopy …” The assessment noted that the main indication for this procedure is obscure gastrointestinal bleeding, which is defined as bleeding of unknown origin that persists or recurs after a negative initial endoscopy. The assessment noted that capsule endoscopy has also been used in the diagnosis and evaluation of Crohn's disease. The assessment noted that some studies have reported a higher diagnostic yield (proportion of patients identified with an apparent abnormality) than the comparator test. The assessment noted, however, in most cases, patients had undergone extensive prior investigations, which would be likely to decrease the apparent diagnostic yield for the comparator procedures. The assessment stated that “[i]t was not possible to determine the relative diagnostic performance (ability to detect correctly both the presence and absence of disease) of wireless capsule endoscopy compared with alternative conventional diagnostic tests” in the assessment of obscure gastrointestinal bleeding. Similarly, with respect to diagnosis of Crohn's disease, the assessment found that the available evidence “is not of sufficient quantity and quality to determine the relative diagnostic performance of wireless capsule endoscopy compared with alternative conventional diagnostic tests in diagnosing unselected patients with suspected Crohn's disease.”

An assessment by the Belgian Health Care Knowledge Center (KCE) (Poelmans, et al., 2006) recommended capsule endoscopy in patients with obscure GI bleeding “when a previous ileocolonoscopy and esophagogastroduodenoscopy were negative.” The assessment found that, “[a]t present, the available evidence is not of sufficient quantity and quality to determine the relative diagnostic performance of CE compared with alternative conventional diagnostic tests in diagnosing patients with CD [Crohn's disease], intestinal polyposis and celiac disease. No conclusions can be made as to whether CE is an effective alternative to other tests. Further research is warranted to determine the place of CE in the management algorithm of OGIB [obscure GI bleeding] and on other potential indications for CE such as CD, intestinal polyposis and celiac disease.”

The American Gastroenterological Association position statement on OGIB (Raju et al, 2007) stated that patients with occult GI blood loss and iron deficiency anemia and negative workup on EGD and colonoscopy need comprehensive evaluation, including capsule endoscopy to identify an intestinal bleeding lesion.

Capsule endoscopy has been used in detecting carcinoid tumors of the small intestine. Guidelines from the National Comprehensive Cancer Network (NCCN, 2008) recommend the use of an Octreoscan for persons who present with carcinoid syndrome to determine tumor location and extent. Appendiceal tumors require abdominopelvic CT. Bronchoscopy, upper gastrointestinal barium swallow with small bowel follow through as indicated, colonoscopy and gastroscopy as indicated to identify the primary site. An MRI of the lung, mediastinum and head, and a CT scan of the chest, abdomen and pelvis may also be helpful, depending on the possible site. For workup of carcinoid tumors of the small bowel, the NCCN guidelines recommend an initial evaluation with an Octreoscan and abdominopelvic CT scan.  For persons with locoregional disease, additional workup is recommended with a GI series with small bowel follow-through as indicated. Enteroclysis or capsule endoscopy are considered optional tests for workup of locoregional disease of the small bowel.

Capsule endoscopy may also be useful for identifying celiac disease of the small intestine in persons with positive serologies where previous intestinal biopsies have been negative. Rondonotti, et al. (2007) found capsule endoscopy comparable to EGD for the diagnosis of celiac disease when there are overt villous changes.  Consecutive patients with signs and symptoms suggestive of celiac disease and positive anti-gliadin and/or anti-endomysial and/or anti-tissue transglutaminase antibodies underwent upper gastrointestinal endoscopy and capsule endoscopy. Duodenal biopsies were classified according to modified Marsh's criteria. Capsule findings were evaluated for the presence of lesions compatible with celiac disease (scalloping of duodenal folds, fissures, flat mucosa, and mosaic appearance). Duodenal histology was normal in 11 and compatible with celiac disease in 32 of 43 patients studied. Using duodenal histology as the gold standard, the performance characteristics of capsule endoscopy for the diagnosis of celiac disease were: sensitivity 87.5% (95% confidence interval 76.1 to 98.9%), specificity 90.9% (95% confidence interval 81.0 to 100%), positive predictive value 96.5% (95% confidence interval 90.1 to 100%), negative predictive value 71.4% (95% confidence interval 55.8 to 87%), positive and negative likelihood ratios 9.6 and 0.14, respectively. Eighteen patients had mucosal changes extending beyond the duodenum, involving the entire small bowel in three. These patients tended to have more severe symptoms, but the difference was not statistically significant. Interobserver agreement for the diagnosis of celiac disease by capsule endoscopy ranged between 79.2 and 94.4%; kappa values ranged between 0.56 and 0.87. The authors concluded that capsule endoscopy shows good sensitivity and excellent specificity for the detection of villous atrophy in patients with suspected celiac disease.

Capsule endoscopy is also being investigated for detecting esophageal pathology. Given Imaging Ltd. (Yoqneam, Israel) received marketing clearance from the FDA in November 2004 for its Given Diagnostic System with PillCam ESO video capsule for imaging the esophagus. The PillCam ESO is being marketed for the diagnosis and evaluation of diseases of the esophagus such as gastroesophageal reflux disease (GERD), erosive esophagitis and Barrett's esophagus, a pre-cancerous condition. The FDA classified the PillCam ESO video capsule as a Class II device that is subject only to general regulatory controls.

The PillCam ESO is the same size as the PillCam SB (11 x 26 mm); however, miniaturization of electronics has enabled the PillCam ESO capsule to include two video cameras, one at each end of the capsule. Each imager captures two images per second, totaling four images per second. The esophageal transit time of the capsule is brief (less than 5 seconds) when patients ingest the capsule with water in the upright position. The transit time may be lengthened by having the patient ingest the capsule lying horizontally, which may allow visualization of the squamocolumnar junction.

In a feasibility study, Eliakim, et al. (2004) compared the PillCam ESO to conventional upper endoscopy as the gold standard for detection of esophageal pathologies in patients with suspected disorders of the esophagus (n=17). Esophageal pathology was found in twelve of the patients by conventional upper endoscopy and with the PillCam ESO. An additional pathology that was found with the PillCam ESO was considered a false-positive. The authors concluded that this pilot study provides evidence that the esophageal capsule is an accurate, convenient, safe and well-tolerated method to screen patients for significant esophageal disorders; however, the authors stated that further, large-scale studies are necessary to fully assess this diagnostic tool.

A multicenter prospective study by the same investigator group, Eliakim, et al. (2005) compared the PillCam ESO to conventional upper endoscopy in patients with chronic GERD (n= 93) and Barrett's esophagus (n=13). The PillCam ESO identified esophageal abnormalities in 61 of the 66 patients with positive esophageal findings (sensitivity, 92%; specificity, 95%). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the PillCam ESO for Barrett esophagus were 97%, 99%, 97%, and 99%, respectively, and for esophagitis 89%, 99%, 97%, and 94%, respectively. The authors reported no adverse events related to the PillCamESO during the 2-week follow-up period and concluded that it is a convenient and sensitive method for visualization of esophageal mucosal pathology and may provide an effective method to evaluate patients for esophageal disease. The authors reported that future generations of esophageal capsules with higher frame speed are in clinical trials.

The PillCam ESO is also being investigated for use in evaluating patients with esophageal varices.  Potential advantages of capsule endoscopy over EGD is the ability to avoid sedation in patients with liver cirrhosis, and the ability to perform capsule endoscopy during the office visit.  In a pilot study of 32 patients with cirrhosis, the PillCam ESO was compared with EGD in detecting esophageal varices and portal hypertensive gastropathy. Twenty-three patients had esophageal varices at both EGD and PillCam ESO evaluation (Eisen, et al. 2006). The overall concordance between PillCam ESO and EGD was 96.9% for the diagnosis of esophageal varices and 90.6% for portal hypertensive gastropathy. 

De Franchis, et al. (2007) reported on a multicenter clinical trial comparing capsule endoscopy to EGD in detecting esophageal varices. Patients who were undergoing clinically indicated EGD for screening or surveillance of esophageal varices were asked to undergo capsule endoscopy prior to the EGD. EGD was performed within 48 hours of capsule endoscopy. A second investigator read each capsule endoscopy study, blinded to patient history and EGD results. Two hundred eighty five patients underwent capsule endoscopy and EGD, 61 percent of whom underwent the procedures for screening, and the remainder for surveillance of known esophageal varices. Sensitivity, specificity, positive predictive value and negative predictive value for capsule endoscopy compared to EGD were 86.7%, 88.4%, 92.9%, and 79.1%, respectively. Overall agreement was 87.3% (95% confidence interval 83% to 91%). There was complete agreement on varices grade in 82 percent of cases. In three cases, capsule endoscopy did not detect esophageal varices that were considered medium/large on EGD, and EGD did not detect one case of medium esophageal varices seen on capsule endoscopy. In differentiating between two patient management alternatives (i.e., large varices which requires treatment and small varices or no varices which requires monitoring), sensitivity, specificity, positive predictive value and negative predictive value for capsule endoscopy compared to EGD were 84.6%, 96.1%, 89.2% and 94.3%, respectively. The overall agreement of treatment decisions based on esophageal varices size was 93%.

Commenting on the study by de Franchis, et al., Zaman (2008) stated that although the overall performance of esophageal capsule endoscopy was good, the study’s primary endpoint was not met — capsule endoscopy was not equivalent to EGD for detecting varices. Zaman concluded that EGD should therefore continue to be the first-line modality for this application. However, capsule endoscopy should be considered an alternative modality if EGD is contraindicated because of concerns regarding safety or tolerance.

Lapalus, et al. (2006) reported on a study comparing EGD and PillCam ESO in evaluating portal hypertension in 21 patients with cirrhosis. The PillCam ESO accurately assessed the presence or absence of esophageal varices in 17 of 20 patients (85%). The three patients in whom there was a discrepancy between the two procedures were diagnosed with grade 1 varices on EGD and no varices on esophageal capsule endoscopy. The sensitivity of capsule endoscopy for detecting esophageal varices in comparison with EGD as the gold standard was 81.25% (13 of 16), with a 100% positive predictive value, a specificity of 100% (12 of 12), and a negative predictive value of 57.1% (4 of 7). In evaluating the stomach, one patient presented with gastric varices that were diagnosed with both EGD and capsule endoscopy. Portal hypertension gastropathy was diagnosed with EGD in 16 of 21 patients and with capsule endoscopy in 13 of 20 patients. The four patients in whom there was a discrepancy were diagnosed as having gastropathy on EGD but not on capsule endoscopy in three cases, or as having gastropathy on capsule endoscopy but not on EGD in one case.

Guidelines on the prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis from the American Association for the Study of Liver Diseases states the frequency of surveillance endoscopies in patients with no or smal varices depends upon their natural history (Garcia-Tsao, et al., 2007). Upper endoscopy should be performed once the diagnosis is established. In patients with compensated cirrhosis who have no varices on screening endoscopy, upper endoscopy should be repeated in 2 to 3 year intervals. In those who have small varices, upper endoscopy should be repeated in 1 to 2 years. In the presence of decompensated cirrhosis, upper endoscopy should be repeated at yearly intervals.

An assessment by the American Society for Gastrointestinal Endoscopy (ASGE, 2006) found “[t]o date there are limited published data on capsule endoscopy of the esophagus…These preliminary data show an excellent diagnostic yield in cases of erosive esophagitis, Barrett's esophagus, and esophageal varices.”

The American College of Gastroenterology (ACG) (1999) recommends that patients with long-standing GERD symptoms, particularly those 50 years of age and older, undergo an upper endoscopy for evaluating the mucosa for esophagitis. Approximately 20 percent of U.S. adults have symptoms of GERD at least once a week; however, a subgroup of patients with GERD develops severe complications that include erosive esophagitis, stricture formation, Barrett's esophagus, and adenocarcinoma of the esophagus. The ACG state that “patients with chronic GERD symptoms are those most likely to have Barrett's esophagus and should undergo upper endoscopy.” ACG guidelines state that the diagnosis of Barrett's esophagus requires biopsy to determine whether intestinal metaplasia is present. Tissue acquisition can be performed during conventional endoscopy for biopsy.

The PillCam ESO technique is limited because it: (i) does not have the capability of tissue acquisition, and (ii) the rapid transit rate through the esophagus could potentially miss suspected esophageal pathologies. Although Barrett's esophagus rarely progresses to adenocarcinoma (one in 200 patients develop carcinoma per year), no studies have verified that any specific treatment or management strategy has decreased mortality rate from adenocarcinoma (Shalauta and Saad, 2004). Thus, the clinical effectiveness of the PillCam ESO as a potential screening method for suspected Barrett's esophagus is unclear. In addition, approximately 25 percent of persons with Barrett's esophagus have no symptoms of reflux. Given the high prevalence of GERD, it may be prohibitive to screen all patients with GERD symptoms for the development of Barrett's metaplasia (Shalauta and Saad, 2004).

Thus, capsule endoscopy cannot completely replace conventional endoscopy for the evaluation of diseases involving the esophagus and its clinical value as a screening technique for suspected Barrett's esophagus remains unclear. The clinical effectiveness of the PillCam ESO in screening GERD patients for suspected Barrett's esophagus to direct appropriate patients for endoscopic biopsy needs to be demonstrated by large-scale clinical trials published in the peer-reviewed medical literature.

In a prospective, multi-center, blinded study, Lin and colleagues (2007) evaluated the accuracy of esophageal capsule endoscopy (ECE) for the diagnosis of Barrett's esophagus. Major outcome measures included sensitivity, specificity, as well as positive and negative predictive values of ECE for Barrett's esophagus by using EGD results, with histological confirmation as the criterion standard. A total of 96 subjects were enrolled, of whom 90 (94 %) completed the study, including 66 screening and 24 surveillance patients. Esophageal capsule endoscopy was 67 % sensitive and 84 % specific for identifying Barrett's esophagus, diagnosing 14 of 21 cases of biopsy-confirmed Barrett's esophagus. Positive and negative predictive values were 22 % and 98 %, respectively (calculated for screening patients only). Sensitivity for short- and long-segment Barrett's esophagus was similar. The authors concluded that the findings of this study showed that ECE had only moderate sensitivity and specificity for identifying Barrett's esophagus. They noted that ECE in its present form is unsuitable as a primary screening tool for Barrett's esophagus; however, ECE may be used in patients unwilling to undergo EGD.

Johnson (2007) noted that the findings by Lin et al (2007) are contradictory to the favorable results from the study by Eliakim et al (2005). This discrepancy is surprising because some earlier studies had been carried out with capsules that captured only 4 frames per second rather than the 14 frames per second captured by the capsule that was used in the present study. In the validation study, experts who were aware of both the endoscopy and the capsule findings adjudicated final diagnoses; as the current study did not include this protocol, its results could reflect "real-world" use more accurately. Although the convenience, safety, and patients’ tolerance of CE make it an attractive tool for esophageal imaging, at present, this device probably cannot be relied on for the one-time screening to exclude Barrett's esophagus in patients with chronic GERD.

Johnson (2008) commented that two recent studies (citing Sharma, et al., 2008; Quershi, et al., 2008) have demonstrated that esophageal capsule endoscopy is unreliable for detection of BE and has high interobserver variability, particularly with respect to short -segment BE (SSBE). Johnson (2008) concluded that these studies demonstrate that esophageal capsule endoscopy in its current form is not an adequate tool for screening for BE.

Sharma, et al. (2008) reported on a prospective trial involving 100 patients who had GERD symptoms or were under surveillance for BE. All patients underwent esophageal capsule endoscopy, followed by standard upper endoscopy, which was considered the gold standard. The esophageal capsule endoscopy findings were evaluated by investigators who were blinded to the endoscopic findings. BE was confirmed histologically in 45 of the 94 patients who completed the study. Esophageal capsule endoscopy demonstrated a sensitivity of 78%, a specificity of 75%, a positive predictive value of 74%, and a negative predictive value of 79%. The corresponding accuracy for diagnosing erosive esophagitis was 50%, 90%, 56%, and 88%, respectively.

Quershi, et al. (2008) reported on a prospective trial involving patients with short-segment BE (SSBE). Twenty patients with biopsy-proven SSBE underwent capsule endoscopy of the esophagus; images were subsequently reviewed by two experts who had no knowledge about the purpose of the study. Eighteen patients completed the study. BE was identified or suspected in 44% of these patients by one observer but in only 16% by the second observer. The Z-line was identified in all 18 patients by both observers, but there was agreement in only 6 as to whether it was normal or irregular.

American College of Gastroenterology guidelines do not support the use of esophageal capsule endoscopy for Barrett's esophagus (Wang, et al., 2008).  

Capsule endoscopy has not been proven to be of value in detecting conditions in the colon. The major technical limitations of capsule colonoscopy are its requirement for highly effective bowel preparation and the limited frame speed of the current version. The colon is not well visualized with capsule endoscopy because stool obscures the visualization of the colonic mucosa. Visualization of the colon is more difficult than the small intestine because of its slower transit time and larger diameter; it is possible for the camera to miss suspicious areas of the colon simply by being pointed in the wrong direction. An American Cancer Society position statement (Levin, et al., 2003) has concluded that there is no evidence to support the use of capsule endoscopy for detecting colorectal polyps or cancers.

Rex (2008) commented that capsule colonoscopy is similar to computed tomography colonography in having required polyp-size thresholds for referral for polypectomy. Rex stated that, from a cost-effectiveness standpoint, capsule colonoscopy is dominated by colonoscopy when equal adherence is assumed (citing Hassan, et al., 2008). For capsule colonoscopy, improvements in adherence could overcome deficiencies in effectiveness (Rex, 2008). However, there currently is no good evidence of improved compliance with capsule colonoscopy. Thus, although capsule colonoscopy could improve adherence, actual demonstrations of whether and how much improvement could be expected are needed.

The Canadian Agency for Drugs and Technologies in Health (CADTH)'s report on capsule colonoscopy/PillCam Colon (Tran, 2007) stated that there is limited evidence on the use of this technology in imaging the colon. Two small, methodologically flawed pilot studies found that for patients with positive findings (i.e., abnormalities detected), the rates of detection with the PillCam Colon capsule were similar to those obtained with conventional colonoscopy. Larger, multi-center trials that compare CE with colonoscopy are needed. The evidence to support the use of CE in screening for colorectal cancer is also lacking.

Capsule endoscopy is contraindicated in patients with known or suspected gastrointestinal obstruction, strictures, or fistulae. The available literature indicates that an upper gastrointestinal series should be performed prior to capsule endoscopy if the patient is suspected of having intestinal obstruction. In a review on contraindications to capsule endoscopy, Storch and Barkin (2006) stated that the only true remaining contraindications to capsule endoscopy are obstruction/pseudo-obstruction and pregnancy.

The Agile Patency System (Given Imaging, Ltd.) was cleared by the FDA through the 510k process for determining the presence of obstructions or strictures in the gastrointestinal tract through a dissolvable capsule. It supposedly will give physicians confidence that a PillCam video capsule will pass freely in a patient with known or suspected strictures. suspected strictures. Currently, there is insufficient evidence on the performance of this patency system as a technique to evaluate patients with known or suspected strictures prior to using the wireless capsule endoscopy system.

Spada et al (2007) evaluated the safety of the Pillcam in patients with known or suspected radiological stricture, previously tested for small bowel patency using the Given Patency capsule. A total of 27 patients (16 female, mean age of 44.2 years) with known or suspected intestinal stricture were enrolled prospectively: 24 had Crohn's disease, 2 had adhesive syndrome, and 1 had a suspected ischemic stricture. Patients underwent the Patency capsule test. In patients in whom the Patency capsule was excreted intact within 72 hours post-ingestion without occurrence of any adverse event, video capsule endoscopy (VCE) was performed to assess the presence of strictures or other gastrointestinal pathologies. The following parameters were evaluated: transit time of Patency capsules and/or tags from ingestion to excretion, condition of the Patency capsule at excretion, transit time of the Pillcam capsule, the ability of Pillcam capsule to detect intestinal strictures and small bowel pathologies, any adverse events. A total of 25 patients (92.6 %) retrieved the Patency capsule in the stools; 6 patients complained of abdominal pain, 4 of whom excreted a non-intact capsule. Hospitalization was required in 1 (4.3 %) patient with Crohn's disease due to occlusive syndrome. Fifteen patients (65.3 %) excreted an intact Patency capsule after a mean transit time of 25.6 hours without any adverse events. These 15 patients underwent the VCE successfully. The authors concluded that passage of an intact Patency capsule across a small bowel stricture provides direct evidence of functional patency of the gut lumen and allows a safe VCE. Intestinal strictures should not be considered an absolute contraindication for VCE.

Herrerias and colleagues (2008) assessed the ability of the Agile Patency System to help physicians identify which patients with known strictures may safely undergo CE. A total of 106 patients ingested the patency capsule. Fifty-nine (56 %) excreted it intact and subsequently underwent CE. There were no cases of capsule retention. Significant findings on CE were found in 24 (41 %). There were 3 severe adverse events. The authors concluded that these findings suggested that the Agile Patency System is a useful tool for physicians to use before CE in patients with strictures to avoid retention. This group of patients may have a high yield of clinically significant findings at CE. This capsule may determine whether patients who have a contraindication to CE may safely undergo CE and obtain useful diagnostic information.

The Agile Patency System has been reported to cause obstruction requiring urgent intervention. There is currently insufficient evidence from well-designed studies to support the use of the Agile Patency System. In addition, the American Society for Gastrointestinal Endoscopy's Technology Status Evaluation Report on wireless capsule endoscopy (Mishkin et al, 2006) stated that "[t]here is limited information about the new patency capsule. While it is intended to assess the passage of a capsule in patients at risk for intestinal stenosis, there have been reported cases that have required hospital admissions, augmentation of medical therapy, and even surgery. As a result, improvements to the system are being implemented before it can be approved in the United States".

In a prospective, multi-center study, Van Gossum and colleagues (2009) compared CE with optical colonoscopy (the standard for comparison) in a cohort of patients with known or suspected colonic disease for the detection of colorectal polyps or cancer. Patients underwent an adapted colon preparation, and colon cleanliness was graded from poor to excellent. These investigators computed the sensitivity and specificity of CE for polyps, advanced adenoma, and cancer. A total of 328 patients (mean age of 58.6 years) were included in the study. The capsule was excreted within 10 hours after ingestion and before the end of the lifetime of the battery in 92.8 % of the patients. The sensitivity and specificity of CE for detecting polyps that were 6 mm in size or bigger were 64 % (95 % confidence interval [CI], 59 to 72) and 84 % (95 % CI, 81 to 87), respectively, and for detecting advanced adenoma, the sensitivity and specificity were 73 % (95 % CI, 61 to 83) and 79 % (95 % CI, 77 to 81), respectively. Of 19 cancers detected by colonoscopy, 14 were detected by CE (sensitivity, 74 %; 95 % CI, 52 to 88). For all lesions, the sensitivity of CE was higher in patients with good or excellent colon cleanliness than in those with fair or poor colon cleanliness. Mild-to-moderate adverse events were reported in 26 patients (7.9 %) and were mostly related to the colon preparation. The authors concluded that the use of CE of the colon allows visualization of the colonic mucosa in most patients, but its sensitivity for detecting colonic lesions is low as compared with the use of optical colonoscopy.

In an editorial that accompanied the afore-mentioned article, Bretthauer (2009) stated that colonoscopy, CT colonography and colon CE (CCE) should be tested in randomized, comparative trials that allow valid and precise quantification of their effect on colorectal cancer (CRC) incidence and mortality.

Sieg et al (2009) stated that CRC screening with colonoscopy was introduced into the National Cancer Prevention Program in Germany in 2002. As compliance for screening is low (around 3% per year), CCE could be an alternative approach. In this study, feasibility and performance of CCE were evaluated in comparison with colonoscopy in ambulatory patients with special attention to a short colon transit time. Colon CE was prospectively tested in ambulatory patients enrolled for colonoscopy who presented for screening or with positive fecal occult blood test. Study subjects underwent colon preparation and ingested the capsule in the morning. Colonoscopy was performed after excretion of the capsule. Colonoscopy and CCE were performed by independent physicians who were blinded to the results. A total of 38 patients were included. One patient was excluded because the capsule remained in the stomach during the entire period of examination. Another patient had limited time and the procedure had to be stopped when the capsule was still in the transverse colon. Thus, these investigators reported the results of 36 patients (30 men and 6 women; mean age of 56 years, range of 23 to 73 years) who successfully completed CCE and the conventional colonoscopy examination. The capsule was excreted within 6 hours in 84 % of the patients (median transit time 4.5 hours). If oral sodium phosphate was excluded from the preparation, the colon transit time increased to a median of 8.25 hours. In total, 7 of 11 small polyps (less than 6 mm) detected by colonoscopy were identified by CCE. One small polyp detected by CCE was not identified by colonoscopy. In this series, no large polyps were found. One CRC was detected by both methods. The mean rates of colon cleanliness (range from 1 = excellent to 4 = poor) in the cecum (2.1), transverse colon (1.6), and in the descending colon (1.5) were significantly better than in the rectosigmoid colon (2.6), and the overall mean rate during colonoscopy was significantly better than during CCE. No adverse effects occurred. The authors concluded that CCE appears to be a promising new modality for colonic evaluation and may increase compliance with CRC screening. To achieve a short colon transit time, sodium phosphate seems to be a necessary adjunct during preparation. The short transit time is a prerequisite to abandon the delay mode of the capsule. With an undelayed PillCam COLON capsule, a "pan-enteric" examination of the gastrointestinal tract would be possible. They stated that further studies are needed to improve the cleanliness, especially in the rectum and to evaluate the method as a potential screening tool.