Colon capsule endoscopy (CCE) is a minimally invasive technique specifically designed to explore the colon without sedation and air insufflation. CCE may overcome some of the limitations of colonoscopy. Second-generation CCE (CCE-2) was proved accurate in detecting colonic neoplastic lesions when used in average-risk individuals. The evidence to date supports the use of CCE-2 in cases of colonoscopy failure, in patients unwilling to undergo colonoscopy, and when colonoscopy is contraindicated. Other potential applications, such as colorectal cancer screening or diagnostic surveillance of inflammatory bowel disease, require clarification.
Key points
- •
Colon capsule endoscopy (CCE) is a minimally invasive, painless endoscopic tool that allows colonic investigation without requiring intubation, insufflation or sedation.
- •
CCE is not an alternative to colonoscopy, but a complementary test for average-risk patients unwilling or unable to undergo colonoscopy, and cases of incomplete colonoscopy.
- •
For such indications, CCE is advantageous because it is minimally invasive and allows direct visualization of the colonic mucosa with good accuracy, without radiation exposure.
- •
CCE bowel preparation must be exhaustive because fecal remains cannot be removed by CCE. It also needs to promote capsule propulsion through the entire small bowel and then through the colon to the rectum.
- •
The second generation of CCE is an accurate tool for colonic evaluation.
Introduction
Colorectal cancer (CRC) is a leading cause of cancer death around the world, being the second most common cause of cancer-related death in developed countries with 500,000 deaths per year worldwide. The procedure of choice for CRC prevention is colonoscopy, which allows the identification and removal of premalignant adenomatous polyps. Although the risk of colonoscopy-related severe complications is small, conventional colonoscopy is perceived as an invasive and potentially painful procedure, which requires conscious or deep sedation and takes place in an unpleasant setting.
Colon capsule endoscopy (CCE) was initially released in 2006 by Given Imaging (Yoqneam, Israel). More recently the technology has been implemented, and a second generation of CCE is now available. CCE allows a minimally invasive, painless colonic investigation without requiring intubation, insufflation, or sedation, allowing the pursuit of normal daily activities during the procedure.
According to the European Society of Gastrointestinal Endoscopy (ESGE) guidelines, CCE can be used in average-risk patients, in patients with a previous incomplete colonoscopy, in those unwilling to undergo conventional colonoscopy, or in those for whom colonoscopy is not possible or contraindicated.
Introduction
Colorectal cancer (CRC) is a leading cause of cancer death around the world, being the second most common cause of cancer-related death in developed countries with 500,000 deaths per year worldwide. The procedure of choice for CRC prevention is colonoscopy, which allows the identification and removal of premalignant adenomatous polyps. Although the risk of colonoscopy-related severe complications is small, conventional colonoscopy is perceived as an invasive and potentially painful procedure, which requires conscious or deep sedation and takes place in an unpleasant setting.
Colon capsule endoscopy (CCE) was initially released in 2006 by Given Imaging (Yoqneam, Israel). More recently the technology has been implemented, and a second generation of CCE is now available. CCE allows a minimally invasive, painless colonic investigation without requiring intubation, insufflation, or sedation, allowing the pursuit of normal daily activities during the procedure.
According to the European Society of Gastrointestinal Endoscopy (ESGE) guidelines, CCE can be used in average-risk patients, in patients with a previous incomplete colonoscopy, in those unwilling to undergo conventional colonoscopy, or in those for whom colonoscopy is not possible or contraindicated.
PillCam COLON capsule system
The Given Imaging diagnostic system is composed of 3 main subsystems: the ingestible capsule endoscope (second-generation colon capsule), the Data Recorder, and the RAPID workstation. The second-generation CCE (PCC-2) is 11.6 × 31.5 mm in size. It has been endowed with a battery lasting about 10 hours and has 2 cameras, one at each end, with an angle of view of 172° for each camera, allowing a near full visual coverage of the colon. To enhance colon visualization and to save battery energy and video reading, the capsule is equipped with an adaptive frame rate (AFR), which alternates from 35 images per second while in motion to 4 images per second when virtually stationary. At the moment of the ingestion the capsule begins working, using AFR allowing proper visualization of the esophagus, then slows down to 14 images per minute. When small bowel images are detected, the system switches the capsule to the AFR mode. This advanced system for control of capsule image rate is the result of a bidirectional communication between the capsule and the Data Recorder. The new Data Recorder (Data Recorder 3 [DR3]) not only stores the capsule’s incoming images but also analyzes them in real time to control the capsule capture rate of images. When DR3 recognizes that the capsule is virtually stationary, it sets the image capture rate to 4 frames per second. When the DR3 recognizes that the capsule is in motion, it sets the image capture rate to 35 frames per second. The DR3 also assists and guides patients and physicians by means of visual and audio signals throughout the procedure activities. It buzzes, vibrates, and displays instructions on its liquid crystal diode screen to alert the patient to continue the preparation protocol. In practice, when the video capsule has detected intestinal villi, the patient is informed and invited to orally ingest the “booster,” according to the preparation regimen. On completion of the examination, data from the Recorder are downloaded to the Workstation that is provided with dedicated software (RAPID) for video viewing and processing. The new RAPID software has an integrated tool to estimate polyp size. To make the examination interpretations easier, the new RAPID software has flexible spectral intelligent color enhancement to improve image quality and pathologic visualization.
Bowel preparation
The current ESGE guidelines for CCE preparation recommend 4 L polyethylene glycol (PEG) solution administered in split doses (2 L the day before the examination and 2 L on the day of the examination, before capsule ingestion) combined with oral low-volume sodium phosphate (NaP) boosters to assist capsule propulsion and excretion ( Table 1 ).
| Schedule | Intake | |
|---|---|---|
| Day −2 | Bedtime | Senna, 4 tablets (48 mg) |
| Day −1 | All day | Clear liquid diet |
| Evening (7–9 pm ) | 2 L PEG | |
| Examination day | 7–9 am | 2 L PEG |
| 10 am (∼1 h after last intake of PEG) | Capsule ingestion a | |
| After small bowel detection | First boost 30 mL NaP + 1 L water | |
| 3 h after first boost | Second boost b 15 mL NaP + 0.5 L water | |
| 2 h after second boost | Suppository b 10 mg bisacodyl | |
a 10 mg metoclopramide tablet if capsule delayed in stomach longer than 1 hour.
In contrast to conventional colonoscopy, it is not possible to clean the colon during the CCE procedure. Therefore colonic preparation is crucial, as even a small amount of debris could interfere with colon capsule capability in identifying colonic polyps, and ultimately compromise the outcome of the procedure ( Fig. 1 ). Colonic preparation for CCE is not limited to achieving an adequate cleansing level, but is also aimed at distending the colonic wall, filling the lumen with clean liquids, and promoting capsule propulsion and excretion, ensuring that the journey is completed within the battery’s lifetime. Because preliminary studies using the same preparation as colonoscopy (PEG solution) showed low excretion rates (20%), a protocol combining PEG (4 L) and boosts with NaP (75 mL) was adopted, and was demonstrated to allow a complete colon examination in most cases. Subsequent studies proposed modifications in the timing and doses of the components, the inclusion of dietary recommendations (low-residue diet, liquid diet the day before) and suppositories (in case of delayed capsule excretion), prokinetics (for delayed stomach emptying), and different kinds of boosters. In particular, because of concerns related to the administration of NaP, other boosters have been investigated. Caution should be exercised when NaP is administered to the elderly, patients with dehydration or renal disease, and those receiving angiotensin-converting enzyme inhibitors. Unfortunately, studies that tried to replace NaP resulted in unsatisfactory outcomes, namely significant reduction of capsule excretion and completion rate. When considering that cecal intubation rates of higher than 90% and 95% are recommended for routine and screening colonoscopies, respectively, CCE could not be considered an efficient option if only 75% of patients achieve a complete examination, as observed when administering a PEG instead of an NaP booster. Moreover, an incomplete capsule examination, in contrast to an incomplete colonoscopy, tends to leave the left colon uninvestigated. Recently, Rex reported the results of a United States trial in which NaP was replaced by Suprep (sodium sulfate, potassium sulfate, and magnesium sulfate) (Braintree Laboratories Inc, Braintree, MA, USA), maintaining the split dose of PEG. The 91% of capsule excretion rate within 10 hours is comparable with the results of trials in which NaP was adopted. Results of different regimens of preparation are listed in Table 1 . Collectively these studies lead to 2 important conclusions: (1) split regimens of PEG (2 L + 2 L) are recommended to improve the cleansing level; and (2) effective boosters (to date most of the evidence applies to NaP boosters) should be recommended to achieve a reasonable capsule excretion rate. When NaP was included in the preparation regimen, low doses (45–55 mL) were shown to achieve an adequate capsule excretion rate with the advantage of decreasing the risk of NaP toxicity (acute nephropathy, electrolyte imbalance, kidney failure). The role of low-volume–based preparation regimens is not well studied. Preliminary results show that low-volume regimens (2 L of PEG + ascorbic acid) are at least as effective as a 4-L PEG regimen in terms of both cleansing level and excretion rate. If such results are confirmed by further trials, the low-volume regimen of preparation would be an effective alternative that could improve compliance to CCE.
Accuracy
Second-generation CCE (CCE-2) was demonstrated to be a feasible and reliable tool to detect colonic lesions, such as polyps and tumors ( Fig. 2 ). Results of published studies are shown in Table 2 . Overall more than 1100 were involved in comparative trials that used standard colonoscopy as gold standard. The relatively low number of patients studied is a clear limitation, and further data are needed. However, it should be emphasized that these studies show comparable results in terms of accuracy, cleanliness, excretion rate, and safety, suggesting that they accurately represent the actual performance characteristics of CCE-2. The low specificity observed in the European and Israeli trials was mainly related to a consistent number of false-positive cases generated by size mismatching between standard colonoscopy and CCE. Only a minority of false positives was related to findings visualized by CCE and not confirmed by colonoscopy, it being not possible to exclude the risk of missed polyps by colonoscopy (ie, falsely negative at colonoscopy). To date 10 cancers have been detected by conventional colonoscopy in comparative trials: CCE-2 identified cancers in all cases, suggesting a potential 100% sensitivity.
| Authors, Ref. Year | Sample Size (N) | Adequate Cleansing (%) | Excretion Rate (%) | Polyp ≥6 mm | Polyp ≥10 mm | ||
|---|---|---|---|---|---|---|---|
| Sensitivity (%) | Specificity (%) | Sensitivity (%) | Specificity (%) | ||||
| Eliakim et al, 2009 | 98 | 78 | 81 a | 89 | 76 | 88 | 89 |
| Spada et al, 2011 | 117 | 85 | 81 a | 84 | 64 | 88 | 95 |
| Rex, 2013 | 884 | 80 | 91 b | 88 | 82 | 92 | 95 |
| Hagel et al, 2014 | 24 | 90.1 | 71 c | 72.2 | 90.9 | 75 | 100 |
| Holleran et al | 62 | 92 | 73 c | 95 | 65 | 89 | 96 |
b Within 10 hours postingestion.
Clinical indications
Patients Without Alarm Symptoms
Based on the available evidence CCE-2 cannot replace conventional colonoscopy, but it should be considered a complementary test in specific settings. According to the ESGE guidelines, CCE can be used in average-risk subjects who do not appear to be at increased risk of colorectal neoplasia. In this setting a noninvasive test may be considered, and CCE might be preferred over nonimaging tests (ie, fecal tests) because of its ability to detect nonneoplastic conditions that may be regarded as clinically useful (eg, vascular malformations). On the other hand, patients with alarm symptoms (because of symptoms or signs, or a family or personal history of CRC) are at increased risk of colorectal neoplasia. These patients should be referred to colonoscopy. For patients who are not compliant with colonoscopy, the use of CCE should be considered and discussed.
Incomplete Colonoscopy
To date, most of the evidence for CCE applies to patients with a previous incomplete colonoscopy. According to the US Multi-Society Task Force (USMSTF) on Colorectal Cancer, gastroenterologists performing colonoscopy should be able to achieve cecal intubation in 90% of all cases and in 95% of screening colonoscopies. In the literature, incomplete colonoscopy rates range from 5% to 15%. The most frequent causes of incomplete colonoscopy include left-sided angulations caused by diverticular disease or postsurgical adhesions, extensive looping or stenosing colorectal cancer, or patient intolerance. At present, following an incomplete colonoscopy patients are usually referred for additional tests, given the risk of missed neoplasia in the nonvisualized colon. Options include radiologic imaging (computed tomographic colonography [CTC] or barium enema), colonoscopy using different endoscopes (pediatric or variable-stiffness colonoscopes, balloon-assisted enteroscopes, cap-assisted or water-immersion technique) or with anesthetist assistance. CTC, also known as virtual colonoscopy, has been shown to be substantially more effective than double-contrast barium enema for the detection of large colorectal polyps and colorectal cancer. CTC is now recommended by the American Gastroenterological Society as the imaging modality of choice in cases of incomplete colonoscopy. When compared with other endoscopic modalities, CCE has the unique characteristic of examining the colon in a proximal to distal direction. Colonic segments that are not explored because of an incomplete colonoscopy (the right colon) are the ones visualized first with CCE. Several studies have shown that CCE can allow visualization of colonic segments not visualized by previous incomplete conventional colonoscopy in 83–98% of cases. In this setting, CCE can detect additional findings that would have been missed, as they were localized in unexamined segments ( Table 3 ). European studies suggest that CCE yields significant findings and guides further workup in 23–45% of cases. The optimal timing of CCE after an incomplete colonoscopy, and how to proceed with the preparation if CCE is performed immediately after colonoscopy, are not known. This issue is important because it affects whether patients are asked to perform an additional preparation. CCE immediately after an incomplete colonoscopy would also allow the endoscopist to complete an examination of the colon on the same day without rescheduling or referring the patient to other physicians. To date, only one prospective trial from Greece that used the first generation of colon capsule showed that CCE can be performed effectively and safely immediately after incomplete colonoscopy, thus minimizing patient burden. Patients who underwent same-day CCE received the second part of the bowel preparation as described by Schoofs and colleagues.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
