Fortunately, in 1981 an Israeli physician, Gavriel Iddan, DSc, began to develop a video camera that would fit inside a pill.² Twenty years later, patients like Sally can now take advantage of state-of-the-art technologic advances like capsule endoscopy.

The investigation begins

Anemia may have multiple causes. Medically speaking, it can occur as a side effect of drugs or chemotherapy, chronic renal insufficiency, iron deficiency, reduced red cell lifespan, and low levels of erythropoietin. Mechanically, it can be brought on by blood loss secondary to menstruation or as a result of uterine fibroids. It can be caused by gastric ulcers, colon polyps or tumors, vascular disorders, or celiac disease. Blood loss can be gradual and go undetected by both the patient and the physician for long periods of time. At some point, though, the blood loss can become too significant to be overlooked or ignored. Patients may suffer syncopal episodes, fatigue, decreasing blood counts, and melenic and occult positive stool.

Locating a bleeding source in the GI tract is a matter of analysis, investigation, and evaluation, and it is a true process of elimination. Historically, the small intestine has occupied a “diagnostic void.” This roadblock is directly related to the difficulty of examining the small intestine. Without being able to visualize the entire duodenum, the jejunum, and the ileum, a diagnosis can remain unconfirmed indefinitely, despite the use of multiple diagnostic procedures.

In cases like Sally’s, an esophagogastroduodenoscopy (EGD) is performed first. A gastroscope (a flexible tube with a camera at one end) allows the physician to visualize and evaluate the inside lining of the esophagus, stomach, and duodenum. Bleeding sources in the upper portion of the digestive tract may be caused by ulcerations, esophagitis and/or gastritis, gastric polyps, or stomach cancer. If the EGD is negative, a colonoscopy will likely be the next procedure performed. This test analyzes the six feet of large intestine extending from the anus to the terminal ileum. Potential bleeding sources that can be found in the colorectal area are diverticulosis and/or diverticulitis, colitis and inflammatory diseases (Crohn’s colitis, ulcerative colitis, radiation proctitis), telangiectasias, arteriovenous malformations, colon polyps, and/or a colon mass or cancer. If both of these procedures yield negative results, the next area to evaluate is the small intestine. In an effort to make medical advances in visualizing that elusive area, a new procedure was born.

Fantastic voyage

In 2001, the U.S. Food and Drug Administration approved the Given Diagnostic Imaging System®.² Reminiscent of science fiction movies, where people and equipment were miniaturized to get inside the hidden realms of the body, the endoscopy capsule weighs just one-seventh of an ounce and is the size of a large vitamin. It holds a color video camera, lights, a wireless radiofrequency transmitter, and enough battery power to take 60,000 color images. The capsule is made of a material that is resistant to the powerfully corrosive elements of both stomach and digestive enzymes.

This process has also been termed Wireless Capsule Endoscopy.³ It makes it possible to visualize, for diagnostic purposes, the entire length of the small intestine. The images provided by the camera cover a 140-degree viewing field and can achieve a magnification level of 1:8. The tissue depth explored covers from 1 mm to 30 mm.

Over the eight-hour time period the capsule requires to pass successfully through the GI tract, it is capable of transmitting two frames of pictures per second to the data recorder that is secured to the patient’s waist. Gastric emptying time ranges from one hour to several hours, depending on patient bowel transit time and motility. Transit through the small intestine on the average, however, takes about two to five hours.

A capsule endoscopy is an effective diagnostic tool in the evaluation of myriad conditions including chronic or unexplained diarrhea, unexplained abdominal pain, weight loss, iron deficiency anemia, malabsorption disorders, and obscure GI bleeding.⁴ It can also be used as a diagnostic tool in the evaluation of Crohn’s disease and other inflammatory disorders of the GI tract, and in the evaluation of polypoid lesions.⁴ As an adjunct to standard endoscopic diagnostic procedures, it is an important complement to existing diagnostic tests and tools.^5,6,7

At the current time, the most important diagnostic benefit of a capsule endoscopy is in the evaluation of obscure GI bleeding — defined as bleeding of unknown origin that persists or recurs after a negative initial or primary endoscopy (upper endoscopy and/or colonoscopy).⁸ In about 5% of patients who present with a GI bleed, no cause for it can be determined. Some 27% of these patients have later been diagnosed with lesions in the small bowel.⁸

Tool for tool

Evaluated against the more conventional diagnostic tools commonly employed to evaluate diseases of the small intestine, capsule endoscopy has proven to be superior.^9,10 It yields better results than both push enteroscopy (the use of an overtube with an enteroscope) and the standard radiological small bowel evaluations—the small bowel barium series and the barium enema.^11,12 Here’s why: Upper endoscopy and colonoscopy do not extend deeply into the small bowel area. Radiological views of the small intestine also yield a limited accuracy. CT scans and MRIs do not analyze the area successfully.¹³ An enteroscope, longer than a gastroscope and designed to view deeper portions of the small bowel, commonly curls in upon itself the farther into the intestine it extends. This results in a limited visibility of this area. Push enteroscopy does not significantly improve the passage of the scope into the lower levels of the small bowel. At the same time, it greatly raises the risk of perforation of the intestine.⁵

There are some drawbacks to capsule endoscopy as well. Although the literature does not state that patients have reported pain or discomfort as a direct result of ingesting the capsule, it can become impacted, either at a site of narrowing of the lumen of the intestine, or in the presence of a bowel obstruction. Patients, who have had GI surgery or a previous bowel obstruction, have a higher risk of potential capsule impaction than those without a history of such events. In the rare event such an impaction does occur (less than 0.5%), the capsule must be removed surgically.¹⁴

In some situations, the procedure may be indicated to identify the site of the lumen narrowing, as a presurgical diagnostic test, for example. A known mechanical intestinal obstruction, however, is a definitive contraindication to the use of this diagnostic tool. Additionally, a capsule endoscopy should not be performed in the presence of a Zenker’s diverticulum, intestinal pseudoobstruction, long-term use of nonsteroidal antiinflammatories, pregnancy, and/or in the presence of large, and/or numerous diverticula.

Patients with implanted electronic devices, such as pacemakers and defibrillators, may experience electrical interference from the capsule endoscope. Additionally, magnetic resonance imaging is contraindicated until the capsule has been eliminated from the body in the stool.¹⁴ Hospital inpatients on telemetry must be carefully observed as the capsule may cause mechanical interference with cardiac monitoring.

Moving on

The procedure itself is relatively simple. Iron supplements are discontinued 24 hours before the test and patients are NPO for 12 hours before ingesting the capsule. The “pill” is smooth and easy to swallow. In patients unable to swallow a pill, or those with a history of gastroparesis, the device can be placed endoscopically.

The patient stays with the clinician during ingestion about 45 minutes while required information is entered into the data recorder. This process initializes the recording device, while concurrently allowing medical personnel the opportunity to review the procedure and pertinent instructions with the patient. The capsule itself is activated by removing it from its magnetic holder. Immediately after the capsule is swallowed with a small amount of water, images begin to pass through the camera. This information, in turn, is transmitted to sensors that are connected to a data recorder. The recorder is worn on a belt around the patient’s waist while the digestive tract is being visualized. The capsule moves through the GI tract with the help of peristalsis. The capsule’s progress during its journey is imperceptible and the patient can continue with normal activities of daily living.

Most studies are initiated in the morning to accommodate the pill’s “transit” time. At approximately 10 AM, the patient can start drinking clear liquids. Around noon, the patient can begin eating solid food. At this point, the camera will have passed any areas of potential debris buildup.

As the camera progresses through the intestine, it continuously captures images of the inside lining of the small intestine. These images are transmitted to sensory pads that have been placed on the patient’s body, which, in turn, communicate with a recording device the patient is wearing around the waist. When the eight-hour period is over, the patient returns to the office to remove the recorder. At this point, the captured images are downloaded and transferred to a computer program for subsequent evaluation by the physician. The video capsule itself is expelled naturally in the patient’s stool during a regular bowel movement.

Signs of success

Although this cutting edge technology is quite new, it has still been able to exhibit, to date, a diagnostic accuracy rate approaching almost 55%.¹⁵ Patients are able to tolerate it easily, it is not an invasive procedure, it can be performed on an outpatient basis, and it can be used to diagnose a wide range of GI diseases. And most important, it dramatically increases the compliance ratios with the requirements of the procedure, because it is patient-friendly and noninvasive.^9,10,16,17

The high cost of a capsule endoscopy and the extensive amount of time required by the physician to analyze the results can sometimes make this a prohibitive procedure.¹⁸ The facility must pay $62,000 to purchase the equipment. The capsule itself costs $900 per patient. Adding together the equipment amortization costs per patient, the facility’s fees, the physician’s fee, and the cost of the capsule itself, the procedure can cost somewhere in the range of $2,000 to $3,000 per patient, per procedure. Insurance company reimbursement is poor when analyzed against the time requirements upon the physician during the analysis phase of the study.⁹

As a capsule endoscopy is a purely diagnostic tool, a push enteroscopy is still required to acquire a tissue biopsy, or to perform therapeutic procedures, such as cauterization of an actively bleeding site. A barium radiological study is still required to visualize areas of stricture within the colon. Last, due to the size of the capsule, this technique cannot be used as a diagnostic tool in children under 10 years of age.¹⁸

Into the future at warp speed

Capsule endoscopy is a revolutionary step forward in patient management and care. It is the test of choice after negative colonoscopy and upper endoscopy in the evaluation of bleeding of unknown origin, and is quickly becoming an invaluable diagnostic tool to the gastroenterologist. It has the potential to detect diseases of the GI tract at very early stages and has a valuable role to play in the diagnostic and therapeutic treatment of GI disorders.

Over time, capsule endoscopy has proven to be a major scientific advance in the diagnostic evaluation of diseases of the small bowel. It has revealed the reasons for obscure gastrointestinal bleeding in between 50% to 70% of the patient population examined — a significant increase over more standardized approaches, such as push endoscopy and barium studies.¹⁹

The original capsule, which sold under the name M2A™ (mouth to anus), has been subsequently renamed the PillCam SBTM (small bowel). This version still has a camera at one end, and takes two pictures per second for a total of eight hours. The newly developed PillCam ESOTM is used to evaluate the esophageal area. This capsule has a camera at both ends and takes 14 pictures per second over a period of 5 minutes.²⁰ Although the esophagus can easily be visualized through more conventional means, patients may ultimately prefer the capsule method, because it avoids discomfort and requires no sedation.

Current indications for the use of this diagnostic technique include investigating the causes of obscure GI bleeding, overt and recurrent bleeding, and the detection of small bowel injuries secondary to the use of NSAIDs. Evolving indications include the evaluation of chronic diarrhea and malabsorption symdromes.²¹ The capsule is also used in the diagnosis of suspected small bowel tumors and to investigate the presence of Crohn’s Disease, although at this point in time, many insurance companies are not covering the cost of this procedure for the evaluation of these

GI disorders²²

Ongoing research into additional uses of this technique is proceeding in the areas of GI bleeding without hematemesis and the evaluation of chronic abdominal pain in situations where it is difficult to distinguish between the presence of an organic disease or a pain syndrome.²² Video capsule endoscopy appears to equal duodenal histology in detecting celiac disease, as well as in surveillance of polyposis syndromes that affect the small bowel.²³

While the role of the capsule is still being determined, new and additional applications continue to emerge. Capsule endoscopy has recently been approved for use in children aged 10 years and older.²¹ Although this diagnostic technique is currently employed more in Europe than in the U.S., more locations in the U.S. are using this procedure. Although currently limited to diagnostic applications, future indications for the pill are unlimited. Designs of the future may have expanded capabilities that could include fluid sampling, mucosal biopsy, and more controlled movement of the capsule through the system. Major advances have been made in a short time, and more exciting advances can only be on the way.

The view from the inside: Normal villi (left) and Crohn’s disease (right). The capsule endoscopy makes it possible to visualize, for diagnostic purposes, the entire length of the small intestine. The images provided by the camera cover a 140-degree viewing field and can achieve a magnification level of 1:8. The tissue depth explored covers from 1 mm to 30 mm.  (SOURCE: Photos courtesy of Given Imaging.)

*Name has been changed.