Saturday, March 9th, 2013

Abstract and Introduction

Abstract

Capsule endoscopy for the colon was introduced to allow an alternative screening method to the invasive classic colonoscopy. The results of initial studies have shown inferior detection rates of colonic polyps by the colon capsule. In this paper we aim to review and summarize the recent advances in wireless capsule endoscopy of the colon. Publications regarding the use of colon capsule with new technology, as well as personal experience, were reviewed. Since the introduction of the first generation of the colon capsule, many improvements have been made to create a better capsule endoscope. These include a wider angle of view, a faster adaptable frame rate and a new data recorder which is able to control the capsule activity during the transit through the bowel. Recent studies show these improvements had a direct effect on the colon capsule performance, leading to a better diagnostic yield. Recent advancements in the technology of the wireless colon capsule endoscope offer the option to screen patients for colonic polyps noninvasively. Colon capsule endoscopy may become relevant for assessment of extent of inflammatory bowel disease.

Introduction

Wireless capsule endoscopy of the digestive tract was conceived of by Gabi Iddan and Paul Swain independently [Iddan and Swain, 2004; Iddanet al. 2000]. Instead of competing they decided to join forces. In 1997 Paul Swain swallowed the first wireless capsule endoscope in Israel. The transmitted images were of poor quality but the possibility of wireless transmission from the digestive tract to an outside receiver (recorder) was proven to be possible. This opened the way for a controlled study. Capsule endoscopy of the small bowel was compared with push enteroscopy in patients with occult gastrointestinal bleeding. The capsule outperformed push enteroscopy by a ratio of 2 : 1 [Lewis and Swain, 2002]. Based on these findings the US Food and Drug Administration (FDA) approved this device for investigations of the small bowel in 2001.

Capsule endoscopy was uniquely fit to examine the small bowel. Direct inspection of the mucosa of the small bowel was made possible without invasive tools and laborious challenging procedures, either for the patient or physician.

The developers of capsule endoscopy sought to extend this methodology to the colon. The thinking was that the colonic surface could be inspected without undergoing colonoscopy which is invasive, uncomfortable (air insufflation), requires sedation and carries a small but not negligible risk of complications. Such a device would lend itself to screening the population for colonic polyps and cancer. However, there were major obstacles that had to be overcome.

Evolution of Capsule Endoscopy

Capsule Orientation and Camera
The large bowel is anatomically different from the small bowel, and has several challenges. The capsule endoscope has the camera on one end and the radio transmitter unit on the other end. The capsule can enter the small bowel either with the camera or with the radio transmitter leading. Since the small bowel is narrow, the length of the capsule (27 mm) prevents it from turning around. The capsule thus remains oriented in the same direction as it enters the small bowel and transmits images that cover the entire length of the small bowel. However, the colon has a much wider diameter. This allows the capsule to flip around its own axis. Therefore, the camera can change directions: at times the front of the capsule with the camera may be leading and at times the camera may be oriented in the opposite direction. So with a standard capsule there are areas which would be screened twice (when the capsule flips around its axis) and areas that were not to be screened at all.

The engineers solved this problem by adding another camera, so that both ends of the capsule transmit images. This guarantees that the entire surface of the colon is screened no matter how many times the capsule rotates around its own axis in the colon (Figure 1).

PillCam colon 2. Size: 31mm–11mm.

The Battery Life
The capsule has to travel through the stomach and small bowel to reach the colon. This journey is time consuming. While the capsule travels through the intestinal tract to reach the colon it transmits images. This journey therefore also consumes the energy stored in the two capsule batteries. The drained batteries would cease transmission of images before the capsule reaches the end of the colon. Two changes were made to solve this problem. A third battery was added which made the capsule slightly longer (31mm) and a sleep mode was added to economize on energy. The transmission of images ceases for an hour and a half after ingestion to allow travel to the target area. With increased energy stores (third battery) and decreased energy consumption (sleep mode) the capsule transmits images from the entire colon.

Visualization of the Mucosa and Bowel Cleansing

The surface of the colon is covered by debris and fecal material and if the colon is not perfectly clean, the mucosa of the colon will not be visualized by the capsule. The colon thus has to be vigorously cleansed before the capsule is deployed. This bowel cleansing has to be superior to the cleansing process applied for conventional colonoscopy since no suction of liquid remnants is possible during capsule endoscopy. The bowel preparation is as described in the first clinical pilot study [Eliakimet al. 2006]. This regimen has achieved good quality cleansing of the colon in 80% of cases.

Three studies were performed with this first colon capsule [Van Gossumet al. 2009; Eliakimet al. 2006; Schoofset al. 2006] which demonstrated three important features: the capsule could transit through the entire colon while taking images; the bowel was adequately clean in 80% of cases; and, finally, the capsule was able to identify pathological findings such as polyps, tumors, inflammation and diverticular disease. The disappointment with this colon capsule was the lower sensitivity in identifying patients with colonic polyps as compared with standard colonoscopy [Van Gossumet al. 2009].

Recent Advances: Pillcam COLON 2

Following on from the results of the first study, the engineers in Yoqneam went back to the drawing board and designed a new colon capsule system. This PillCam COLON 2 has the following new features:
1. The angle of view has been widened from 154° to 172° for each camera, thus offering a panoramic view;

2. The recorder receiving the transmission signal from PillCam COLON 2 was revolutionized. This new recorder is endowed with artificial intelligence and is turned into an active participant of the study. This ‘thinking’ recorder (Figure 2) also communicates with the capsule. In turn, the capsule listens to the ‘thinking’ Data Recorder 3 and executes orders received by it.

Data Recorder 3 with the online viewer.

Data Recorder 3 recognizes that the capsule is in the stomach. At this time the capsule is maintained at a low transmission rate of six images per minute in order to save energy. Data Recorder 3 is also able to detect when the capsule leaves the stomach and enters the small bowel. At this point the recorder instructs the capsule to raise its transmission rate to four images per second. In addition, Data Recorder 3 can also identify whether the capsule is stationary or moving. If the capsule is in motion Data Recorder 3 orders the capsule to raise the transmission rate to 35 images per second. The execution of this order takes significantly less than a fraction of a second.
Data Recorder 3 recognizes location of the capsule and how long it has been there. If after an hour the capsule is still in the stomach, it will notify the patient with a sounding a signal and will send vibrations to the sensor belt to inform the patient to ingest a prokinetic agent such as domperidone. After passage of the capsule from the stomach into the small bowel, the Data Recorder 3 emits a beeping signal while vibrating the sensor array and displays on the LCD screen a message that informs the patient to ingest a booster laxative which will accelerate the passage of the capsule through the small bowel

This new design of the capsule endoscopy platform and the technical achievements are very impressive. Yet the critical question to be asked is whether this new capsule endoscope (with its thinking and talking recorder and capsule with new technical features such as a panoramic view and an adjustable frame rate of 4 to 35 images per second) is just an impressive high-tech toy or does PillCam COLON 2 lead to improved diagnostic performance?

A recent five-center feasibility study addressed this question [Eliakimet al. 2009]. A total of 104 patients participated in a blinded prospective study comparing PillCam COLON 2 capsule endoscopy with standard colonoscopy. The primary endpoint was the identification of patients having colonic polyps. The sensitivity to diagnose patients with polyps improved from an average of 60% in previous studies to 90%. This greater diagnostic yield has to be credited to the advanced technological changes in the COLON 2 system for the following reason. The design of this study was very similar to the three studies published on the original colon capsule. The adequacy of the bowel preparation was similar in all studies (). The only feature which separates the PillCam COLON 2 study from the previous three trials with the lower diagnostic sensitivity is the technological improvement. The findings of the Israel multicenter trial have been reproduced recently in Europe (data were presented at an oral presentation by G. Costamagno at UEGW 2010). The calculated specificity is relatively low. This is partly due to the fact that protocol restraints forced (colonoscopy was referred to as the gold standard) the authors to count truly missed colonic polyps by colonoscopy as false-positive capsule findings. The literature has documented that colonoscopy often misses adenomas and even colon cancer [Heresbachet al. 2008; Bressleret al. 2004; Rex et al. 1997]. It is thus not surprising that capsule endoscopy recognized several polyps missed by conventional colonoscopy. Furthermore, the mismatch in polyp size assessment by colonoscopy and capsule endoscopy also led to the so-called false-positive findings by capsule endoscopy. The negative predictive value of 97% is very high and is of clinical relevance. Colon capsule endoscopy will be offered as an outpatient procedure. Subjects who require a screening to check the presence of polyps can undergo PillCam COLON 2 capsule endoscopy. If the study is negative physicians will be able to exclude the presence of polyps with 97% reliability and inform their patients. Hassan and colleagues, using a Markov statistical model, have demonstrated that if adherence to capsule colonoscopy (with an assumed sensitivity of 65%) was only 4% higher than that of standard colonoscopy in screening populations for colonic polyps (using the original colon capsule technology), it would save the same amount of lives as colonoscopy [Hassan et al. 2008]. If we consider the 88% sensitivity rate of PillCam COLON 2 the projected numbers would be even more favorable for this second generation COLON 2 capsule. Hassan and colleagues indicate that colon capsule endoscopy may be a cost-effective procedure for colon cancer prevention.

Table 1.Comparing cleansing adequacy between the different studies.

	PillCam Colon studies			PillCam Colon 2 study
	Eliakimet al. 2006	Schoofset al. 2006	Van Gossumet al. 2009	Eliakimet al. 2009
Adequate cleansing	84%	88%	72%	78%

Conclusions
In the past 9 years wireless capsule endoscopy has firmly established its presence in the practice of gastroenterology. Dramatic technological improvements have created a new wireless capsule endoscopy platform. These advances have opened the door to clinically apply PillCam COLON 2 for outpatient colon polyp screening programs. This method will diagnose the presence and extent of inflammatory bowel disease in the small bowel and colon. The future is here and the outlook looks bright for colon screening technology.

References
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Eliakim, R., Fireman, Z., Gralnek, I.M., Yassin, K., Waterman, M., Kopelman, Y. et al. (2006) Evaluation of the PillCam Colon capsule in the detection of colonic pathology: results of the first multicenter, prospective, comparative study. Endoscopy 38: 963–970.

Eliakim, R., Yassin, K., Niv, Y., Metzger, Y., Lachter, J., Gal, E. et al. (2009) Prospective multicenter performance evaluation of the second-generation colon capsule compared with colonoscopy. Endoscopy 41: 1026–1031.

Hassan, C., Zullo, A., Winn, S. and Morini, S. (2008) Cost-effectiveness of capsule endoscopy in screening for colorectal cancer. Endoscopy 40: 414–421.

Heresbach, D., Barrioz, T., Lapalus, M.G., Coumaros, D., Bauret, P., Potier, P. et al. (2008) Miss rate for colorectal neoplastic polyps: a prospective multicenter study of back-to-back video colonoscopies. Endoscopy 40: 284–290.

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Iddan, G.J. and Swain, C.P. (2004) History and development of capsule endoscopy. GastrointestEndoscClin N Am 14: 1–9.

Lewis, B.S. and Swain, P. (2002) Capsule endoscopy in the evaluation of patients with suspected small intestinal bleeding: Results of a pilot study. GastrointestEndosc 56: 349–353.

Rex, D.K., Cutler, C.S., Lemmel, G.T., Rahmani, E.Y., Clark, D.W., Helper, D.J. et al. (1997) Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies. Gastroenterology 112: 24–28.

Schoofs, N., Deviere, J. and Van Gossum, A. (2006) PillCam colon capsule endoscopy compared with colonoscopy for colorectal tumor diagnosis: a prospective pilot study. Endoscopy 38: 971–977.

Van Gossum, A., Munoz-Navas, M., Fernandez-Urien, I., Carretero, C., Gay, G., Delvaux, M. et al. (2009) Capsule endoscopy versus colonoscopy for the detection of polyps and cancer. N Engl J Med 361: 264–270.

Funding

This research received no specific grant from any funding agency in the public, commercial, or notfor-profit sectors.

Conflict of interest statement

Samuel N. Adler, MD, has been a consultant for Given imaging.
TherAdvGastroenterol. 2011;4(4):265-268. © 2011 Sage Publications, Inc.