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Capsule endoscopy: What role for this new technology?

During this noninvasive procedure, the patient swallows a pill-sized camera and clinicians can visualize the fine mucosal detail of the small intestine.

Christina Beard, PA-C, MPAS; John E. Poulos, MD, MSci, FACG; Janelle Kalle, PA-C; Arvind Kumar, MD, FACG; Valli Kodali, MD, FACG, FACP, AGAF

The authors practice at Fayetteville Gastroenterology Associates, Cumberland Research Associates, and Valley Medical Associates in Fayetteville, North Carolina. They have indicated no relationships to disclose relating to the content of this article.

In 1981, Dr. Gavriel Idan began to develop a capsule-sized camera that could be swallowed by patients to examine the small bowel. This device was initially released as the M2A capsule,^1,2 and subsequent modifications led to the current PillCam device used to perform capsule endoscopy (CE). The 11-mm 3 26-mm PillCam is watertight and acid-resistant, and it contains a battery that can provide power for up to 8 hours³ (see Figure 1).

How CE works GI peristalsis propagates the PillCam through the GI tract while the device records luminal detail in a 140-degree angle of view. PillCam captures two images per second using a light source to illuminate its field and then transmits these images to a small data recorder worn by the patient² (see Figure 2). The capsule also contains a frequency transmitter, which sends signals to sensors that are adhered to the patient’s abdomen. Analysis of the strength of the signal from the transmitter reveals the location of the capsule in the GI tract and also permits the examiner to determine the location of abnormalities seen on the images.³ When battery power is depleted, the capsule switches to beacon mode and continues to send a signal to the data recorder about its location. Images are then downloaded from the data recorder to a specialized computer workstation, where the images are processed into a video to be viewed. These images can be paused, slowed, magnified, and reversed by the viewer, and reports can be generated for review with the patient and referring physicians.⁴

The morning of the examination, the patient presents to the endoscopist’s office. There sensors are applied to the abdomen and connected to the data recorder, which is attached to the patient’s waist. The patient swallows the capsule with a glass of water to facilitate ease of ingestion and, within 1 minute of the camera’s activation, is free to leave the office and go about daily activities. Patients are advised to avoid interference from any potential radio transmissions, powerful electromagnetic fields, sweating, and bending.¹ Cellular phones, fax machines, and computers may be used freely.⁵ The patient can have no food or water for 2 hours after swallowing the capsule; after that, only water is permitted until 4 hours after the procedure, when a light snack may be eaten. After approximately 8 hours, the examination is complete and the patient returns to the office for removal of the equipment.⁶ The patient is instructed to monitor bowel movements for passage of the disposable capsule. One study of 21 patients found that the mean time from ingestion of the capsule to passage per rectum was 31.25 hours (range, 8-73 hours).¹

A role for PAs The average time needed to read and evaluate the downloaded images is approximately 60 minutes.⁷ Physician assistants and other appropriately trained nonphysician clinicians can be used to screen examination results, thereby reducing physician reading times and improving cost-effectiveness. The use of nonphysician clinicians to screen CE images and mark abnormalities has revealed a high level of agreement between significant findings noted by the screener and the gastroenterologist, with sensitivities for the detection of lesions greater than 90%.^8,9

The current Medicare reimbursement rate for the technical and professional component of CE varies by state, ranging from $800 to $1,250.¹⁰ The procedure’s cost is covered by most insurance carriers for the evaluation of iron deficiency anemia, Crohn’s disease, or occult GI bleeding. Widespread media attention has made it necessary for practitioners to become familiar with the indications and applications of CE.

CASE REPORTS

Case 1 A 32-year-old male presented to the emergency department (ED) complaining of diarrhea with hematochezia for 3 to 4 days. He denied hematemesis, weight loss, anorexia, recent antibiotic use, exposure to illness, travel, or a history of any similar illness. He had no significant medical, surgical, family, or social history. On examination, he was febrile. The cardiopulmonary examination was unremarkable except for hypotension and tachycardia. The abdominal examination was benign, with normal bowel sounds and a soft, nontender abdomen without organomegaly. A test for fecal occult blood was positive. Laboratory results were as follows: hemoglobin, 3.9 g/dL; hematocrit, 11.4%; mean corpuscular volume, 87.7 μm³; and platelets, 225,000/μl. Electrolyte values and tests for hepatic function were unremarkable.

The patient was transfused with 4 units of packed RBCs. Colonoscopy showed fresh blood throughout the colon, which appeared to be emanating from above the terminal ileum, along with diverticulosis and hyperplastic sigmoid polyps. There was no evidence of colitis. Upper endoscopy and a small bowel series were normal, and Meckel’s scan was negative.

The patient was stable at discharge and was followed as an outpatient until, 3 months later, he had a similar episode of diarrhea and hematochezia and required hospitalization. He was again anemic (hemoglobin, 10.7 g/dL), a bleeding scan was negative, and colonoscopy revealed ileitis and colitis. Biopsies of the terminal ileum suggested Crohn’s disease. The patient was placed on prednisone and mesalamine. Over the next 8 months, his clinical course waxed and waned; he required another hospitalization for severe symptomatic anemia, and he underwent another colonoscopy with biopsy of the terminal ileum, which showed no evidence of Crohn’s disease.

At this point he underwent CE to determine the etiology of recurrent GI bleeding. The examination revealed erosions within the stomach and ileum, as well as active bleeding throughout the terminal ileum and proximal colon. He was treated for Crohn’s ileocolitis with 6-mercaptopurine (Purinethol) and infliximab (Remicade) infusions, after which his abdominal pain, diarrhea, and bleeding resolved.

Case 2 A 49-year-old male presented to the ED with 3-day history of intermittent epigastric pain that radiated to his back. The abdominal pain was exacerbated by eating and relieved by drinking water. He denied fever, chills, nausea, vomiting, melena, hematochezia, diarrhea, constipation, or weight loss. His medical history was significant for type 2 diabetes requiring insulin, coronary artery disease, heart failure, left bundle-branch block, chronic renal insufficiency, obesity, hypertension, and hyperlipidemia. The surgical history was noncontributory. The physical examination was essentially within normal limits except that the stool examination was guaiac-positive. Laboratory testing revealed iron deficiency anemia with a hematocrit of 28.5%.

Esophagogastroduodenoscopy (EGD) revealed a short segment of Barrett’s esophagus with no dysplasia, benign gastric polyps, and duodenitis; biopsies for Helicobacter pylori were negative. Colonoscopy showed adenomatous polyps, sigmoid diverticulosis, and internal hemorrhoids. At outpatient follow-up, the patient reported intermittent episodes of melena and persistent anemia. He then underwent CE, which showed multiple small, punctuate, nonbleeding arteriovenous malformations and small, nonbleeding erosions in the ileum.

DISCUSSION

The initial evaluation for patients presenting with occult GI bleeding and/or anemia usually involves EGD and/or colonoscopy with ileoscopy (see the algorithm “Evaluation of occult GI bleeding”). More extensive endoscopic visualization of the duodenum, jejunum, and ileum may involve enteroscopy and surgical intraoperative enteroscopy.¹¹ These procedures are invasive, may require purgatives, and utilize sedation. Endoscopic procedures may also overestimate bleeding sources because of trauma from the procedure itself, and they cannot extend through the entire bowel.^12,13 These procedures do, however, permit samples to be taken for biopsy and any underlying bleeding sources to be removed, ablated, or treated.

Radiologic studies such as small bowel follow-through and enteroclysis are indirect examinations that require administration of contrast material and radiation exposure. These studies may be associated with a high false-negative rate because they cannot evaluate fine mucosal detail.⁴ Tagged RBC scans have been associated with poor sensitivity, and the diagnostic value of angiography depends on clinical evidence of active and ongoing bleeding.¹⁴

Intraoperative enteroscopy is an option for small bowel evaluation; however, this is an invasive surgical procedure that requires exploratory laparotomy. The enteroscope is introduced either orally or via an enterotomy, and then the surgeon pleats the small bowel over the endoscope. This evaluation is both diagnostic and therapeutic, but it is reserved for patients who are deemed healthy enough for a surgical procedure.¹¹

CE in context CE avoids the risks associated with sedation and radiation. It is noninvasive and may not require the patient to miss work. The most common indications for CE are GI bleeding and to aid in the diagnosis of small bowel tumors and Crohn’s disease.^5,6,15-18

There are few contraindications to CE, but one is GI obstruction.⁵ There is a role for examination of the small bowel with a small bowel series prior to ingestion of the capsule in patients with a history of radiation exposure or previous surgeries, in order to avoid capsule obstruction due to luminal narrowing. Capsule obstruction is a well-known complication that may necessitate surgical removal. Pennazio and colleagues reported a 5% rate of surgical intervention due to capsule retention.¹⁸ A patency capsule the size of a video capsule but made of a material that disintegrates if it becomes lodged in an intestinal stricture is now available.¹⁹ The patency capsule emits a radio frequency signal so that it and the location of the stricture can be determined.

Other relative contraindications are pregnancy, GI motility disorders, or large diverticuli within the small intestine. No reports document the risk of the capsule becoming lodged in colonic diverticuli, and this condition is not listed as a contraindication.⁶ Recently, the relative contraindication for CE in patients with cardiac pacemakers has been called into question.²⁰ CE has shortcomings—for example, it does not permit lesions to be biopsied or ablated or bleeding to be controlled.

Comparative studies Several studies have compared CE with other modalities for the evaluation of small bowel pathology. Ell and colleagues compared push enteroscopy with CE in localizing a bleeding source in patients with chronic GI bleeding.¹⁴ Criteria for admission to the study included a history of active GI bleeding within the previous 6 months, and 49% of patients had been previously evaluated with EGD, colonoscopy, enteroclysis, or angiography. Push enteroscopy identified definite sources of bleeding in 9 of the 32 patients (28%), and in one patient, endoscopic treatment was performed on an angiodysplastic lesion. CE had a diagnostic yield of 66% for finding definite bleeding sources in 21 of 32 patients. The authors concluded that CE had a higher diagnostic yield than push enteroscopy for identifying sources of chronic GI bleeding and could decrease the number of procedures performed on patients with chronic GI bleeding if used after a negative EGD and colonoscopy.¹⁴

Mata and colleagues also compared CE and push enteroscopy in patients with both occult and overt GI bleeding who had undergone a previous unrevealing EGD and colonoscopy.²¹ CE had a diagnostic yield of 73.8% compared to 19% by push enteroscopy for identifying the source of small bowel bleeding. Note that authors of this study found that CE findings modified treatment plans in 22% of patients. The most common findings were angiodysplasias (45%), jejunal ulcers (10%), and small bowel tumors (6%). Enteroscopy may be complementary to CE in its ability to provide hemostasis and treatment of lesions that have been identified by CE and are within reach of the endoscope.

Selby and colleagues attempted to identify clinical factors that could increase the yield of CE.²² This study included 92 patients with obscure-overt and obscure-occult GI bleeding who had undergone at least one negative EGD and colonoscopy. Patients were divided into two groups: one with overt bleeding and one with anemia. Demographic features, mode of presentation, number of previous procedures or colonic cleansing failed to influence the likelihood of finding a lesion. The most common abnormalities discovered were angiodysplasias, followed by small bowel tumors and ulcerations. CE led to therapeutic intervention in 38% of patients with positive findings. This study suggested that capsule endoscopy might be cost-effective if used early in the workup of a patient with obscure GI blood loss.²² Evaluation of published data indicates that the most common findings with CE are angiodysplasias, followed by small bowel ulcerations secondary to Crohn’s disease or use of NSAIDs and small bowel tumors^7,15,18,21 (see Figure 3).

CE has also been found to be effective in diagnosing and determining the extent of Crohn’s disease. Chong and colleagues evaluated 22 patients with known Crohn’s disease and 21 patients without Crohn’s disease and then attempted to compare enteroscopy and enteroclysis with CE. For patients with Crohn’s disease, CE proved to be more sensitive in detecting lesions in 81% of patients in comparison to positive findings of 18% utilizing enteroscopy and 23% utilizing enteroclysis. Treatment changes were instituted in 70% of patients who had lesions detected with CE.¹⁷

CE has also been compared with small-bowel imaging and ileocolonoscopy in patients with both suspected and established Crohn’s disease.²³ In this comparative study, 28 patients with established Crohn’s disease were compared with 11 patients with suspected Crohn’s disease. Of note, 26% of patients were excluded from the study because of critical strictures seen on radiologic studies; however, the majority of these patients had undergone previous abdominal surgery. CE showed a positive predictive value of 100% and a negative predictive value of 77%. Radiographic imaging missed the diagnosis in 72% of patients, and endoscopy was nondiagnostic in 10% of patients.²³

Limitations of CE A disadvantage of capsule endoscopy is the possibility of an incomplete study, which can be the result of decreased visualization due to chyme or failure of the capsule to reach the cecum because of a small bowel motility disorder or gastroparesis. Studies have evaluated the use of purgatives and promotility agents in improving gastric and small bowel transit time and examined the effects of such medications on the quality of the images obtained.

Dai and colleagues evaluated the use of a polyethylene glycol (PEG)-based solution (compared to the standard preparation of nothing by mouth 12 hours before the procedure).²⁴ The CE study was considered completed if the capsule was able to pass through the ileocecal valve. The PEG group had a 97% completion rate in comparison to the 76% completion rate seen in the standard fasting group. The authors believed that the PEG solution helped to speed small bowel transit time by stimulating peristalsis. Whether increasing small bowel transit resulted in missed findings was not determined. This study also suggested that the PEG group had improved visualization of the bowel mucosa.

Metoclopramide (Reglan) given 15 minutes before CE has also been evaluated and shown to result in a 97% completion rate in comparison to a 76% completion rate in a control group undergoing standard fasting prior to the procedure.²⁵ Mean gastric transit time was prolonged in the control group in comparison to the metaclopramide group; however, there was no significant difference in mean small bowel transit times.

There may also be a role for repeat imaging utilizing CE if the initial study is negative. Bar-Meir and colleagues evaluated 20 patients with persistent iron deficiency anemia and a negative GI workup that included EGD, colonoscopy, and CE.²⁶ Repeating CE in patients with a history of occult bleeding may reveal additional findings in 35% of patients and lead to a change in management in 10% of cases.²⁶ The prime indication for repeating CE is recurrent bleeding or decreased visibility due to poor preparation.²⁷ The yield of finding a source may also be significantly improved if the study is performed during an episode of active bleeding.

The studies discussed in this review have shown that CE has a higher diagnostic yield for small bowel mucosal abnormalities than does radiographic imaging or enteroscopy. If performed early, CE may expedite the diagnosis and at the same time be cost-effective by helping to avoid repeat procedures and hospitalizations.

CE is currently being utilized for the noninvasive diagnosis of esophageal varices and Barrett’s esophagus,^28,29 but this application may be limited because it cannot provide diagnostic tissue sampling for surveillance of Barrett’s esophagus or treatment for varices. Further, the cost of using CE in esophageal disorders may be up to 5-fold higher than the cost for EGD.

Future applications At some point, CE may be used to label the bowel wall, sample luminal contents, biopsy the mucosa, provide therapeutic ablation of lesions, or control the movement of the device.⁵ CE is also being investigated as a diagnostic tool in the evaluation of celiac sprue and chronic abdominal pain.^30,31 Other theoretical improvements include longer battery half-life in order to evaluate colonic disease.

CE has revolutionized the field of gastroenterology by becoming the test of choice for evaluation of the small bowel. Health care providers should be aware of the uses, limitations, and diagnostic possibilities of CE in order to guide their management of patients with small bowel pathology.

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