Aetna considers capsule endoscopy medically necessary for the following indications:

1. To investigate 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, diarrhea, fever, elevated white blood cell count, elevated erythrocyte sedimentation rate, weight loss, or bleeding) without evidence of disease on conventional diagnostic tests, including small-bowel follow-through and upper and lower endoscopy (esophagogastroduodenoscopy (EGD) and colonoscopy).

3. 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 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 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.

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.”

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 recent 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%.

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 wwere 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.

Capsule endoscopy has not been proven to be of value in detecting conditions in the colon. 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.

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.