Enteroscopy: Endangered by the Capsule?

Since the inception of endoscopic examinations, physicians have wanted to obtain direct visualization of the entire gut. Standard endoscopic and colonoscopic exams view only small amounts of the proximal and distal ends of the small bowel. Endoscopic examination of the entire small bowel has remained elusive. Push enteroscopy was the first step in the endoscopic evaluation of the intestine. Initially colonoscopes, both adult and pediatric, were used to evaluate the entire duodenum and proximal jejunum. On average, a 160 cm long instrument can be advanced 40 cm beyond the ligament of Treitz. Currently, 2.1 - 2.5 meter long push enteroscopes have greatly improved the depth of insertion and visualization of the small bowel and it is now possible to inspect the jejunum in its entirety. Examination of the distal small bowel has previously been achieved using sonde and rope-way techniques [1]. Both investigations are lengthy and quite uncomfortable, even painful. The medical community has largely abandoned these exams.

An endoscopic capsule (Given Imaging Ltd, Yoqneam, Israel) has been developed to obtain images from the entire small bowel. Developed by Dr. Gavriel Iddan in 1981, the capsule, which measures 11 × 26 mm, contains four LEDs (light-emitting diodes), a lens, a color camera chip, two batteries, a radiofrequency transmitter and an antenna [2]. The camera is a CMOS (complementary metal oxide semiconductor) chip. This chip requires less power than the CCD (charge-coupled device) chips presently found on video endoscopes and digital cameras, and it can operate at very low levels of illumination. The capsule obtains two images per second and transmits the data via radio frequencies to a recording device worn about a patient's waist. Once the acquisition time is reached, the recording device is downloaded to a computer workstation whose software provides the images to the computer screen. The capsule is disposable and does not need to be retrieved by the patient. It is passed naturally. An average of 50 000 images are obtained during an 8-hour examination.

The initial report of the use of the capsule was published 2 years ago, detailing the quality of the capsule’s images in ten healthy volunteers [3]. The capsule was subsequently studied in nine dogs [4]. Colored beads ranging in size from 3 to 6 mm were sewn into the canine small intestine. Between nine and 13 beads were placed in each dog. Capsule endoscopy was able to identify significantly more beads than push enteroscopy. Following this study, a short report of capsule endoscopy use on a compassionate basis was published. Four patients with obscure gastrointestinal bleeding were described in whom bleeding sites were identified with capsule endoscopy [5]. The first clinical trial was completed last year and push enteroscopy was compared with capsule endoscopy in 21 patients with obscure gastrointestinal bleeding [6]. Capsule endoscopy was superior to push enteroscopy in the evaluation of obscure bleeding. Capsule endoscopy enabled a diagnosis in 11/20 (55 %) and findings included angioectasias, fresh blood, a tumor, and an ileal ulcer. Push enteroscopy enabled a diagnosis in 6/20 (30 %); all findings were angioectasias. No additional diagnoses were made by push enteroscopy and the capsule identified lesions found distally in the small bowel, not reachable by push enteroscopy. The 95 % confidence intervals were 13.65 %.

Thus, capsule endoscopy appears to be the answer to the long-standing desire for complete endoscopic examination of the entire small bowel and it provides this in a noninvasive way. The need for this technology is clear. In this issue, Dr. Landi and colleagues describe the long-term outcome in patients with obscure bleeding investigated with push enteroscopy [7]. The authors show how truly difficult it is to care for these patients. Nearly one-third of patients with isolated iron-deficiency anemia rebleed, as do one-half of patients with known angioectasias of the small bowel. Improved diagnostic abilities would most likely lead to improved prognosis. This lesson was learned when using sonde enteroscopy, where the deeper one looked into the small bowel the more information was obtained. This improved diagnostic ability is especially relevant in addressing the primary concern of physicians who see patients with obscure bleeding, that is, the possibility of occult malignancy. Cancer of the small bowel is uncommon and unfortunately, due to the limitations of previous diagnostic testing, such as the low diagnostic yield of small bowel series, cancer of the small bowel historically carries a poor prognosis. Studies have shown that if it is diagnosed early, prognosis is improved, and other studies have shown that approximately 10 % of patients with obscure bleeding have a tumor of the small bowel [8]. In the study of Landi and colleagues, a patient with iron-deficiency anemia and a negative push enteroscopy subsequently presented with obstruction from an ileal adenocarcinoma. The second major concern of physicians caring for patients with obscure bleeding is control of the transfusion requirement. Obstacles to this have included: limited enteroscopic intubation, which restricts the knowledge about the extent of disease and the depth to which therapy can be provided; the lack of effective medical therapy beyond transfusion; and the difficulties with current surgical intervention when coupled with intraoperative enteroscopy.

Utilizing capsule endoscopy, the evaluation of patients with bleeding in the future will be very different from current practice. Capsule endoscopy may become the third test in the evaluation of patients with gastrointestinal bleeding, when upper endoscopy and colonoscopy give negative findings. In the patient with active bleeding, capsule endoscopy can confirm the small bowel as the site of bleeding, providing a location. If the results of the investigation are negative, this may indicate that the bleeding is actually colonic in origin. In the patient with active bleeding within the small intestine, the capsule findings will guide further evaluation and therapy. A patient with a small-bowel tumor detected by capsule endoscopy will proceed directly to laparoscopic surgery. If the site of bleeding is identified to be in the proximal small bowel and there is no mass, push enteroscopy will be used to re-identify the site and cauterize the lesion. In cases where a distal small bowel site is identified, surgical intervention coupled with intraoperative enteroscopy will be necessary. Since the entire small bowel has been examined in the capsule investigation, surgery can be targeted and a laparoscopically assisted approach, coupled with intraoperative enteroscopy to examine only the suspected area, will be performed. This will simplify the surgical options. Indeed, difficulties now encountered in the management of patients with colonic diverticular bleeding will be avoided in the future, since the right colon is easily examined with the capsule. The capsule does not disturb normal processes and thus the presence or lack of blood in the right colon during an episode of bleeding can provide guidance superior to that of colonoscopy or bleeding scans when the clinician is trying to determine a site of blood loss. In patients with isolated iron deficiency or a more occult or intermittent type of bleeding, capsule endoscopy will be used similarly to identify an intestinal bleeding lesion and thereby direct subsequent testing or treatment. The early diagnosis of tumors of the small bowel will be obtained and those patients with negative findings will be reassured. There is little doubt that practice guidelines will change with increased experience of using capsule endoscopy.

Dr. Lewis is a member of the Medical Advisory Board for Given Imaging Ltd.

References

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• 3 Iddan G, Meron G, Glukhovsky A, Swain P. Wireless capsule endoscopy.  Nature. 2000;  405 417
• 4 Appleyard M, Fireman Z, Glukhovsky A. et al . A randomized trial comparing wireless caspsule endoscopy with push enteroscopy for the detection of small-bowel lesions.  Gastroenterology. 2000;  119 1431-1438
• 5 Appleyard M, Glukhovsky A, Swain P. Wireless-capsule diagnostic endoscopy for recurrent small-bowel bleeding.  NEJM. 2001;  344 232-233
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• 7 Landi B, Cellier C, Gaudric M. et al . Long-term outcome of patients with gastrointestinal bleeding of obscure origin explored by push enteroscopy.  Endoscopy. 2002;  34 355-359
• 8 Berner J, Mauer K, Lewis B. Push and sonde enteroscopy for obscure GI bleeding.  Am J Gastroenterol. 1994;  89 2139-2142