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Hello. I am Dr. David Johnson, Professor of Medicine and Chief of Gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia. Gastroesophageal reflux disease (GERD) is a common condition, and we know that it is associated with a condition called Barrett’s esophagus, which is a precancerous condition. But when is it appropriate to send patients [with GERD] for endoscopy to screen them for Barrett’s esophagus? New recommendations come from the American College of Physicians (ACP), who put forth a very pragmatic document titled “Upper Endoscopy for Gastroesophageal Reflux Disease: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians.”

As background, we know that reflux disease is very common. Nearly 40% of the US population has a symptom of reflux disease, such as heartburn or regurgitation, at least once a month. And we know that nearly 10% to 15% of those patients experience those symptoms at least weekly, and often more than that. But if you said that everyone with reflux needs to be screened for Barrett’s esophagus, unless that disease was very prevalent and very high risk for progression to cancer, the wheels would come off very quickly from a cost-containment standpoint and in health economics evaluations.

Although we screen and survey for Barrett’s esophagus, we have no data from longitudinal studies that show that we reduce the risk for esophageal cancer or cancer-related death in the patients who undergo surveillance strategies.

We know from recent epidemiologic studies from Europe that for patients with nondysplastic Barrett’s, without low-grade or high-grade dysplasia, those patients have a 0.1% to 0.5% per patient-year risk of progression to more serious disease and cancer. For patients with high-grade dysplasia, the risks are considerably higher: up to 6% to 19% per patient-year. Those patients obviously need to be seen and undergo ablative strategies. Nonetheless, for the overall population of patients with Barrett’s, the risk of progressing to cancer is fairly low. Finally, if you focus only on heartburn, 40% of patients with esophageal cancer do not report any heartburn, so we cannot use heartburn as a predominant screening tool.

There are demonstrable risk factors for Barrett’s esophagus, however, and factors that relate to Barrett’s progressing to cancer. We know [that Barrett’s-related cancer is] a fairly prevalent disease, with a particular bias toward men. More than 80% of the cancers are in men. We know that it has a gender- and age-related bias for men over the age of 50. If we look at patients and say “gastroesophageal reflux disease in men,” there starts to be a strategic risk stratification toward that population. But if you look at women, the risk stratification is not there. In fact, women with GERD have less cancer risk than men who have asymptomatic GERD. Therefore, screening women for Barrett’s esophagus and risk for Barrett’s cancer is equivalent to screening men for breast cancer. When a woman mentions that she has reflux disease and you say, “Bingo. You need to be screened for Barrett’s,” think about it: Do you screen your men for breast cancer? Women, even if they have symptomatic reflux, have the same risk [for esophageal cancer] as men have for breast cancer. This is important as we weigh the cost and economic strategies and as we come to the best practice recommendations from the ACP.

What are the ACP recommendations? First, if patients have classic alarm features — dysphagia; heartburn associated with complications such as bleeding, nausea, and vomiting; obstructive symptoms; or weight loss — those warrant endoscopy. That is a no-brainer. Second, if patients have severe or erosive esophagitis when they undergo endoscopy, and it is not clear whether there is Barrett’s when they have the endoscopy, it is reasonable to bring those people back to document whether they do or do not have Barrett’s. That is true for men and women.

Patients who are not responding to 4-8 weeks of twice-daily dosing of a proton pump inhibitor (PPI), or to once-daily dosing of the extended-release dexlansoprazole, should undergo endoscopy. I think that is a reasonable, pragmatic recommendation. Also, if patients have a history of stricture and have recurrent symptoms, the ACP recommends that those patients be referred for endoscopy.

The rubber hits the road when it gets to “whom do you screen for Barrett’s?” In no circumstance do they recommend that women without alarm features be screened for Barrett’s esophagus. Based on the evidence, that is very pragmatic and gets back to screening men for breast cancer. ACP recommends that men over age 50 years, including those with GERD symptoms but no alarm features, men who have hiatal hernia, and those with some other cofactor, such as smoking, should be screened. We do know that truncal obesity is not as much a risk as is abdominal obesity. So, patients who are obese, who are smokers, who are overweight, who have an elevated body mass index, who are male and over age 50, and who have GERD symptoms — those are patients who should be considered for one-time endoscopy screening for Barrett’s. If they do not have Barrett’s, they do not need to come back.

These best practice strategies should lead to refinements in the referrals from primary care to gastroenterologist. When patients are sent in to be screened for Barrett’s esophagus, it is hard for us to say no to our primary care colleagues. We need to start to turn off the spigot at the home base. Lest we throw stones, however, gastroenterologists also overutilize Barrett’s surveillance strategies. We know that from a number of studies. We need to start being a better team, defining the patients for appropriate screening, and using more cost-economic evaluations. I suspect we would see no change in clinical outcomes. These are best practice recommendations. I hope these will guide you in your next discussions with patients who have GERD when they say, “Isn’t this associated with esophageal cancer? Do I need to be screened?” We can start to put some evidence behind our recommendations. These guidelines from the ACP go a long way toward that; they are written by an excellent group of experts and provide pragmatic recommendations that we can use in our clinical practices.

I am Dr. David Johnson. Thank you again for listening.

References

Shaheen NJ, Weinberg DS, Denberg TD, Chou R, Qaseem A, Shekelle P; for the Clinical Guidelines Committee of the American College of Physicians. Upper Endoscopy for Gastroesophageal Reflux Disease: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2012;157:808-816.

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.

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
Bressler, B., Paszat, L.F., Vinden, C., Li, C., He, J. and Rabeneck, L. (2004) Colonoscopic miss rates for right-sided colon cancer: a population-based analysis. Gastroenterology 127: 452–456.

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.

Iddan, G., Meron, G., Glukhovsky, A. and Swain, P. (2000) Wireless capsule endoscopy. Nature 405: 417.

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.

The Digestive Health Clinic is always striving to expand its expertise and knowledge by attracting physicians with a diverse range of training and experience. In 2013, Digestive Health Clinic will be welcoming two new additions to our team of experts; Dr. Jason Wong and Dr. Michael Chan.Each of these new physicians brings a unique skill set to our clinic.

Dr. Jason Wong has started practising endoscopy at the Richmond Hill location. Dr. Wong was trained in general surgery at McMaster University and has been practising general surgery and endoscopy since 1999. He currently has hospital privileges at Rouge Valley Centenary Health Centre, where he is the surgeon in charge of management information systems. In 2005 Dr. Wong was the surgeon in charge of setting up the Minimal Access Surgery (MAS)suite at Rouge Valley, the first of its kind to be offered in a community hospital in the GTA. He has been pivotal in helping to train surgeons in MAS techniques.Dr. Wong is also fluent in Cantonese. We are delighted to have Dr. Wong bring his expertise in state of the art technology and innovation to the Digestive Health Clinic.

We look forward to working with Dr. Michael Chan. He graduated from Queen’s University and has been a practicing surgeon since 1991. He is a Thoracic Surgeon and currently has hospital privileges at Rouge Valley Centenary Health Centre. Dr. Chan speaks fluent Cantonese.