Introduction

The first endoscopic video capsule was initially developed by Iddan and Meron, two Israeli engineers. The capsule and the workstation for processing images were originally marketed by Given Imaging Ltd (Yoqneam, Israel). It was approved for clinical use by the FDA in August 2001, and EC approval followed in May 2002. Since then, other manufacturers have produced similar systems. Olympus (Olympus Optical Co., Ltd, Tokyo, Japan) markets the ‘Endocapsule’ system, while more recently IntroMedic (Seoul, South Korea) have developed the ‘MiRoCam’ and the Chonqing Jinshan Science and Technology Group from China have developed the ‘OMOM’ capsule.

1 Technical principles

Development of the first capsule (Fig. 1) was based on three scientific advances: a CMOS (complementary metal oxide silicone) microchip capable of producing an image comparable with that obtained with a CCD camera; an ASIC (application-specific integrated circuit) system, which allows integration of a small, low-energy video transmitter; and miniature high-power lighting such as an LED (light-emitting diode). These three components are placed in a capsule measuring 1.1 cm × 2.6 cm that can be swallowed. The field of vision obtained is 140°. It is weighted so that it retains its longitudinal orientation for approximately 80% of its intestinal journey, and it passes through the body naturally. The system also comprises a series of sensors which are placed on the surface of the patient’s abdomen and detect signals emitted by the capsule. These are transmitted to a high-frequency tape recorder, contained in a case and worn on a belt by the patient, before transfer to a workstation. The capsule is eliminated in the stools and is a single-use device. This description corresponds to the system developed by Given Imaging Ltd. Since then, the capsule has been improved and is available under the name ‘PillCam SB’, characterized by a wider angle of vision (156°), better resolution (65 536 pixels), and an increased depth of field. The ‘EndoCapsule’, ‘MiRoCam’ and ‘OMOM’ capsules differ in using a CCD rather than CMOS sensor (Fig. 2) to capture images. Studies comparing the ‘Pillcam’ and ‘Endoscapsule’ have not demonstrated any differences in diagnostic yield in patients with obscure gastrointestinal bleeding. The ‘MiroCam’ capsule (Fig. 3) has longer-life batteries (11 h), is smaller in size (11 × 24 mm), has a larger number of pixels (102,400), takes three images per second, and transmits data using conduction through body tissues. This requires constant contact with the mucosa, which may be a limiting factor. Comparative studies with the other two systems are currently underway. The ‘OMOM’ capsule (27.9 mm long, 13 mm diameter, and 6 g weight) is significantly bigger than the others (24–26 × 11 mm and 3.4–3.6 g weight).

Figure 1 Development of the Given Imaging system.

(Courtesy of Given Imaging Ltd.)

Figure 2 Olympus Endo-cap system: antennae and case.

(Courtesy of Olympus.)

Figure 3 Intromedic MiroCam system.

(Courtesy of IntroMedic.)

2 Examination procedure

The patient fasts for 12 h before swallowing the capsule. The five 1.2 V nickel batteries are worn by the patient on a belt, along with the 305 GB data recorder for storing the images. The patient may move around freely after swallowing the capsule. It is eliminated in stools in 24–48 h, depending on gut transit. Air bubbles and food residue may impair image quality and in fit patients, bowel preparation is recommended, as it improves mucosal visualization and diagnostic yield. Polyethylene glycol (PEG) solutions or sodium picosulphate can be used. There is some evidence that simethicone reduces air bubbles and improves views. Transit of the VCE capsule may be slower in diabetic patients or those in poor health and, for them, a prokinetic such as erythromycin is recommended.

3 Safety of VCE and contraindications

No harmful effects have been reported in cases of prolonged capsule retention. The presence of a capsule for 2 years in one individual had no adverse consequences. There is, however, a real risk of small intestinal obstruction as a result of stricturing, especially in inflammatory disorders. This risk is approximately 3.6% in large-scale studies and is offset by the fact that capsule retention is often caused by the lesion or lesions requiring examination by VCE in the first place. Surgery with or without endoscopy usually resolves both the problem of retention and the underlying disease at the same time.

To solve the problem of retention, Given Imaging Ltd has developed a calibration capsule, called the ‘M2A Patency Capsule’. If it has not been expelled after 2–3 days, this breaks down spontaneously into small fragments, which easily pass through a narrowed segment. Latest modifications have incorporated two openings at each end of the capsule (the Agile Patency Capsule, Fig. 4), to enhance capsule breakdown. It is important to remember that neither small intestine barium studies nor CT or MR enteroclysis can detect all strictures. It is therefore essential to enquire about the patient’s medical history (complex surgery, use of NSAIDs, radiotherapy of the abdomen, and recent episodes of obstructive symptoms) before carrying out an examination by VCE. The risk of obstruction should be explained clearly before VCE, along with the possibility that a retained capsule may have to be removed endoscopically or surgically. CT or MR enteroclysis or the use of an Agile Patency Capsule is recommended before performing VCE in patients felt to be at risk of small bowel strictures.

Figure 4 Agile patency capsule.

(Courtesy of Given Imaging Ltd.)

4 Indications and results

VCE has already changed the management of patients in the following disorders:

4.1 Chronic obscure gastrointestinal bleeding

This is defined as isolated or recurrent melena, rectal bleeding or iron deficiency anemia with evidence of gastrointestinal bleeding. Patients should have undergone negative upper endoscopy and total colonoscopy before VCE is considered. A positive diagnosis may be found in 55–81% of patients, the yield being higher in those with overt as opposed to obscure bleeding. VCE is superior in detecting lesions responsible for bleeding compared with push enteroscopy (PE), particularly in patients with overt bleeding. Studies have also emphasized the need for examination by VCE as soon as possible after the bleeding episode, the diagnostic yield dropping as time elapses. Finally, the use of a repeat study in patients in whom VCE had initially been negative will yield a diagnosis in a significant number of patients. Two meta-analyses of 14 and 17 studies, respectively, demonstrate that VCE yields a positive diagnosis in 63% of patients compared with 28% for push-enteroscopy. The lesions detected are usually, in decreasing frequency, arteriovenous malformations (Fig. 5), ulceration secondary to NSAIDs, and tumors. When compared with double balloon enteroscopy (DBE), both methods have similar diagnostic yields in obscure gastrointestinal bleeding: 43–60% for DBE and 59–80% for VCE.

Figure 5 (A,B) Arteriovenous malformation.

4.3 Crohn’s disease

VCE detects more intestinal lesions in patients with Crohn’s disease (Fig. 6) than conventional radiological imaging. The lesions usually detected are mucosal: erosions, purpuric lesions, ulceration, aphthoid lesions, and strictures. Some practical conclusions are shown in Box 1.

Figure 6 Crohn’s disease of the small intestine. (A) Stenosis. (B) Ulcer.

Box 1 The role of VCE in Crohn’s disease

• VCE is not indicated for diagnosis in patients with Crohn’s confirmed by other radiological or endoscopic investigations.

• VCE is useful if Crohn’s disease is suspected clinically or from laboratory tests or during recurrence if the radiological and endoscopic picture is normal.

• VCE is useful in patients with indeterminate colitis to detect small intestinal lesions.

• VCE is recommended in a patient with known disease if the discovery of small intestine lesions will influence the long-term management strategy.

• Detection of jejunal ulcerative lesions may predict early recurrence in a patient who has undergone ileocecal resection.

One of the problems in evaluating VCE in Crohn’s disease is the lack of reliable objective criteria for diagnosis. Scoring indices are under evaluation, based on three parameters: edematous appearance of villi, the presence of ulcers and the presence of strictures. Although these scores provide a common language to try and quantify the disease activity in the small intestine, they need further validation. Ulcers in the small bowel are not always due to Crohn’s – NSAIDs, lymphoma, radiation, and vasculitis can all cause similar appearances. The risk of capsule retention in CD patients is 5–13% and so small bowel imaging or patency capsule studies should be performed to exclude strictures before VCE is undertaken.

4.4 Celiac disease

Some authors have suggested that VCE could be an alternative to endoscopic duodenal biopsies obtained at OGD, particularly in patients unwilling to undergo the procedure, and could be carried out for: chronic iron-deficiency anemia, children with clinical evidence and laboratory results suggesting celiac disease, patients with anti-transglutaminase antibodies, and atypical symptoms in elderly patients (Fig. 7A,B).

Figure 7 (A,B) Celiac disease. (C) Enteropathy associated T-cell lymphoma (EATL) complicating celiac disease.

VCE in combination with DBE is, moreover, the best way of examining patients with celiac disease who have warning symptoms (weight loss, anemia and abdominal pain), while adhering closely a gluten-free diet. VCE is a useful tool for monitoring patients with celiac disease to detect malignant lesions, i.e. adenocarcinoma or lymphoma (Fig. 7C), particularly if ulcerative jejunitis is present.

4.5 NSAID enteropathy

Ulcers, erosions and stenotic diaphragms or webs are usually found (Fig. 8). The clinical significance of minor lesions accompanying the use of NSAIDs is uncertain, as they are also detected in up to 22% of healthy volunteers participating in the control group in studies of NSAID toxicity.

Figure 8 NSAID toxicity.

4.6 Detection of intestinal tumors

The frequency of these tumors (Fig. 9) in patients examined by VCE for chronic obscure gastrointestinal bleeding is approximately 6–12%, and 60% of these are malignant. Since the introduction of VCE, it has been noted that the most frequent presentation of these intestinal tumors is chronic obscure bleeding rather than abdominal pain, weight loss or obstruction. This means that VCE has the potential to detect these tumors at an earlier stage.

Figure 9 (A) Adenocarcinoma of the small intestine. (B) Carcinoid tumor. (C) Gastrointestinal stromal tumor (GIST). (D) Lipoma.

4.7 Surveillance of familial polyposis

VCE is capable of demonstrating the existence of polyposis (Fig. 10) along the small intestine. Although it may miss duodenal lesions in comparison with PE and DBE, it performs better in the jejunum and ileum. Its use is even more impressive in Peutz–Jeghers syndrome in which it can detect lesions capable of causing intussusception, and demonstrate ulcerated polyps responsible for chronic anemia. Its use is now widely accepted in the surveillance of familial adenomatous polyposis (FAP) associated with duodenal polyps. The same applies in juvenile polyposis. If VCE is used to monitor patients with FAP, it should be kept in mind that it does not detect all lesions in the duodenum, particularly the periampullary region. The duodenum must be investigated by a side-viewing endoscope in these patients. Finally, VCE cannot accurately assess the size of tumors in patients with familial polyposis, and often overestimates this. MR-enteroclysis appears to be better for assessing the size of these lesions.

Figure 10 (A) Peutz–Jeghers syndrome with ulceration. (B) Familial adenomatous polyposis.

Box 2 summarizes the role of VCE in small intestinal disorders.

Box 2 Indications for VCE

• Chronic obscure gastrointestinal bleeding.

• Recurrent iron deficiency anemia.

• Crohn’s disease.

• Celiac disease.

• NSAID enteropathy.

• Small intestinal tumors.

• Surveillance of familial polyposis.

• Other disorders: gastrointestinal amyloidosis, Waldmann’s disease, common variable hypogammaglobulinemia, graft-versus-host disease, radiation enteritis, Whipple’s disease (Fig. 11).

Figure 11 (A) Radiation enteritis. (B) Whipple’s disease.

5 Specific situations

6 Technical aids to reading images obtained by VCE

Precise anatomic localization of the capsule (Figs. 12, 13