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Original article
Colon capsule endoscopy is a safe and useful tool to assess disease parameters in patients with ulcerative colitis Mileidis San Juan-Acosta, Angel Caunedo-Álvarez, Federico Argüelles-Arias, Luisa Castro-Laria, Blas Gómez-Rodríguez, Javier Romero-Vázquez, Alba Belda-Cuesta, Francisco Pellicer-Bautista and Juan M. Herrerías-Gutiérrez Objective Colon capsule endoscopy (CCE) is a new endoscopic technique that is minimally invasive and allows evaluation of the colon mucosa without pain, sedation, and gas insufflation. To date, few studies have investigated the use of CCE in patients with ulcerative colitis (UC). This study compares the ability of CCE and a conventional colonoscopy to assess mucosal disease activity and the extent of inflammatory mucosa in patients with UC. Methods Forty-two patients (27 men, mean age 48.5 years) with known UC and indication for colonoscopy were enrolled in this single-blind, prospective study. All patients underwent CCE, followed by a colonoscopy. The activity and extent of the disease was assessed using Mayo scores and Montreal scores, respectively. Results There was a good correlation between CCE and colonoscopy in disease severity (κ = 0.79; 95% confidence interval: 0.62–0.96) and extent of inflammation (κ = 0.71; 95% confidence interval: 0.52–0.90) observed. The ability of CCE to assess a broad segment of distal ileum led to a change in the diagnosis of UC to ileocolonic Crohn’s
Introduction Ulcerative colitis (UC) is a chronic inflammatory condition that causes continuous mucosal inflammation of the colon, without granulomas on biopsy, and is characterized by a relapsing and remitting course [1]. It affects the rectum and a variable extent of the colon in continuity and its symptoms most commonly include bloody diarrhea, rectal bleeding, or rectal urgency [2,3]. The severity of these symptoms is usually related to the extent of mucosal inflammation and can be observed by colonoscopy [2,3]. The use of a colonoscopy establishes the diagnosis and extent of disease in the majority of UC cases and it is the gold standard for diagnosis and to determine the extent of UC and monitor mucosal status [4]. Visualization of the mucosa affected in UC is essential for many aspects of disease management (including drug dosing and duration, the use of oral and/ or topical treatment, and the decision to deliver intravenous medication or undergo surgery) and can predict recurrence rates and complications related to UC (such as hospitalizations, the need for surgery, or an increase/ change in treatment) according to the degree of mucosal healing [5]. Endoscopic features of mild inflammation are 0954-691X © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
disease in three patients. Bowel preparation was considered adequate in 80% of the patients and no serious adverse events related to the CCE procedure or bowel preparation were reported. Conclusion CCE is a safe and useful method for the evaluation of patients with UC. The ability of CCE to assess distal ileum provides an advantage to colonoscopy as CCE can identify patients who have been incorrectly diagnosed with UC, resulting in a change in their diagnosis to Crohn’s disease. Eur J Gastroenterol Hepatol 26:894–901 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. European Journal of Gastroenterology & Hepatology 2014, 26:894–901 Keywords: colon capsule endoscopy, colonoscopy, PillCam, ulcerative colitis Virgen Macarena Hospital, Sevilla, Spain Correspondence to Federico Argüelles-Arias, PhD, Virgen Macarena Hospital, Dr Fedriani s/n, 41071 Sevilla, Spain Tel: + 34 955 00 88 01; fax: + 34 955 00 88 05; e-mail: [email protected] Received 26 December 2013 Accepted 15 April 2014
erythema, loss of visible vascular pattern, and vascular congestion of the mucosa; moderately active colitis is characterized by complete loss of vascular pattern, with a coarse granular appearance and mucosal friability, blood adherent to the surface of the mucosa and erosions; and severe colitis is characterized by spontaneous bleeding and ulceration [6]. Patients with UC have an increased risk of developing colon cancer, which can been attributed to two factors: the length of time since disease onset and the extent of colon affected by UC [7]. According to a meta-analysis of 116 colorectal cancer studies, the overall prevalence of colorectal cancer among UC patients is 3.7% [95% confidence interval (CI) 3.2–4.2], with incidence rates corresponding to cumulative probabilities of 2% at 10 years, 8% at 20 years, and 18% at 30 years [8]. As such, it is recommended in patients who have had UC for 8–10 years (or 15 years of disease in patients with left-sided colitis) that annual or biannual surveillance colonoscopy with multiple biopsies at regular intervals are performed to detect and avoid colorectal cancer [9–12]. DOI: 10.1097/MEG.0000000000000125
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Colon capsule endoscopy for UC San Juan-Acosta et al. 895
A colonoscopy is one of the main tools used to manage patients with UC as it can assess the diagnosis of UC, the extent of inflammation, and a patient’s response to drugs, and it can be used for colorectal cancer screening; however, a colonoscopy is an invasive and uncomfortable procedure in some patients. Colon capsule endoscopy (CCE) is a new endoscopic technique that represents a minimally invasive imaging system that allows exploration of the colon mucosa without pain, sedation, and gas insufflation. CCE has been used for the screening of colorectal cancer [13–15] and appears to be a promising new modality for colonic evaluation [16]. Furthermore, CCE may be useful for the evaluation of colonic lesions and it could be a good alternative for patients refusing conventional colonoscopy or when it is contra-indicated. To date, a few preliminary studies have shown the feasibility of CCE for the management of patients with known UC [17,18], suggesting that CCE may be useful for monitoring inflammation and screening for colorectal cancer in patients with UC. The aim of this study was to compare the use of CCE with standard colonoscopy in the assessment of mucosal disease activity and extent of inflammatory mucosa in patients with UC.
Bowel preparation and time course of evaluations
An overview of the bowel preparation technique utilized in this study is presented in Table 1. Two days before the examination, patients began a low-residue diet and received 48 mg oral sennosides before bedtime. The following day, patients underwent a clear-liquid diet and drank a 2-l PEG bowel preparation at night. On the day of the examination, patients were to have fasted at least overnight (12 h) and were administered a 2-l PEG solution at 7:00 a.m. A PillCam colon capsule was swallowed by the patient with 20 mg domperidone at 9:00 am. An hour and a half later, RAPID software (Given Imaging Ltd, Yokneam, Israel) was used to verify that the PillCam had moved out of the stomach and then a booster of oral sodium phosphate solution (30 ml) was administered. Three hours later, a second booster of oral sodium phosphate solution was administered to promote distal movement of the PillCam through the bowel and excretion. Bisacodyl suppository was administered only if the capsule was not excreted. The CCE was considered ‘complete’ when the hemorrhoidal plexus was identified. After this, on the same day of the CCE procedure, a standard colonoscopy was performed (Table 1). Colon capsule endoscopy
Methods Patients
This single-blind, prospective, comparative study was carried out at the Virgen Macarena University Hospital in Seville, Spain, from January 2010 to January 2012. Patients aged 18–70 years with UC were enrolled if they had either a suspected flare in disease activity or were due to undergo screening for colorectal cancer. Patients were excluded if they had (a) dysphagia, (b) intestinal strictures (confirmed or suspected), (c) high risk of capsule retention (Crohn’s disease, small bowel tumor, radiation enteropathy, previous intestinal surgery), (d) serious systemic diseases such as heart failure, renal insufficiency, defibrillators, or cardiac pace makers, (e) were allergic or intolerant to sodium phosphate, polyethylene glycol (PEG) solution, domperidone, or bisacodyl suppository, or were (f) pregnant.
Two models of PillCam colon capsule (Given Imaging Ltd) were used in this study. The firstgeneration device measures 31 × 11 mm, acquires images at a rate of 4 frames/s, and has a ‘sleep mode’ of 1 h 45 min, during which the capsule is supposed to travel through the stomach (thus saving energy). The secondgeneration device measures 31.5 × 11.6 mm and has two imagers, one at each end of the capsule. In this device, the angle of view is increased to 172° and to conserve battery energy, the capsule captures images at an adaptive frame rate, alternating from 35 images/s while it is in motion (such as in the transverse colon) to 4 images/s when it is virtually stationary. After swallowing, the capsule works at a low frame rate of 14 images/min until it identifies the small bowel. The new data recorder also assists and guides the medical staff and patient through the procedure. It buzzes, vibrates, and displays Table 1
Written informed consent was obtained from each patient before the two procedures. The study protocol conformed to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Virgen Macarena Hospital.
Bowel preparation
Day
Time
Procedure
−2
All day 19:00–21:00 All day 19:00–21:00 06:00–08:30 09:00 09:00 10:30 13:30 15:00 16:30 19:00
Low-residue diet 48 mg sennosides Liquid diet only 2 l PEG 2 l PEG PillCam ingestion Domperidone (20 mg) 30 ml NaP + 1.5 l water 25 ml NaP + 1 l water Snack (optional) 10 mg suppository bisacodyl Standard colonoscopy
−1 0 (exam day)
Methods of evaluation
All patients underwent CCE and then received a conventional colonoscopy. The extent of mucosal disease activity and inflammatory mucosa during both procedures was recorded for comparison.
NaP, sodium phosphate; PEG, polyethylene glycol.
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instruction numbers to alert the patient to take the laxative booster or that the procedure has terminated. Videos were analyzed using the RAPID software (RAPID 6.0 for CCE1 and RAPID 7.0 for CCE2) by an expert physician in capsule endoscopy (CE) who was blinded to the colonoscopy results and also blinded to the patient’s illness characteristics. Conventional colonoscopy
Conventional colonoscopy (CF-H180 Al; Olympus, Tokyo, Japan) was performed by a physician blinded to the results of the CCE and to the patient’s characteristics. Patients were administered intravenous midazolam (2–5 mg) to attain conscious sedation. All investigators were gastroenterologists with experience in colonoscopy and CCE. Assessments
The extent of mucosal disease activity and inflammatory mucosa was assessed during both the CCE and colonoscopy. To diagnose the extent of disease, lesions were classified as ulcerative proctitis (E1), left-side UC (E2), or extensive UC (E3), on the basis of the 2005 Montreal classification of inflammatory bowel disease (IBD) criteria, which were originally presented at the 2005 World Congress of Gastroenterology [1]. The endoscopic activity of UC was classified using a Mayo score (Fig. 1) that defined UC as either mild, moderate, or severe [19]. Colonic cleansing was also assessed using the Leighton scale [20], which defined response as excellent, good, fair, and poor. Finally, the safety of both processes and the preparation of the bowel were also assessed.
and extent between the endoscopists were assessed using Cohen’s κ coefficient.
Results A total of 47 patients were enrolled in the study. Of these, two patients refused conventional colonoscopy after inclusion, one patient refused CCE, and in two patients, the PillCam capsule never transmitted images after ingestion, leading to technical failure of the CCE. Therefore, 42 patients (15 women/27 men), mean age 48.5 years (range 24–75 years), were included in the analysis. Of these, 23 patients underwent a first-generation CCE and 19 patients underwent a second-generation CCE (Table 2). Feasibility of first-generation and second-generation colon capsule endoscopy
Overall, 85.7% of patients who underwent CCE monitoring completed the evaluation (Table 2). In the group of patients who underwent CCE with a first-generation device, a complete evaluation of the colon was possible in 20 patients (87.0%). Reasons for an incomplete examination were the battery running out of power in the rectum (two patients) and the capsule staying in a duodenal diverticulum (one patient). In this case, colonic mucosa was not seen. In the group of patients who underwent CCE with a second-generation device, a complete evaluation of the colon was possible in 16 patients (84.2%). The causes of incomplete examination were the battery running out of power in the splenic flexure (two patients) and the capsule stopping in a stricture in the terminal ileum (one patient). In this case, colonic mucosa was not seen.
Statistical analysis
Correlation between colon capsule endoscopy and conventional colonoscopy
Statistical analysis was carried out using SPSS (SPSS 17.0; SPSS Inc., Chicago, Illinois, USA). Results were expressed as mean ± SD with minimum and maximum values, and categorical data were expressed as percentage. Differences in the recognition of disease activity
The apparent severity of UC varied between the two evaluations. During the conventional colonoscopy, quiescent (inactive), mild, and moderate disease activity was observed in 24, 12, and six patients, respectively; in contrast, the CCE showed quiescent, mild, and moderate
Fig. 1 ∗ 4309
∗
11908
∗ 4426
∗ 11480
D. F:8 Ex:1 α:N
Conectado a ENDOBASE
Conectado a ENDOBASE
Normal
Mild
Conectado a ENDOBASE
Moderate
Conectado a ENDOBASE
Severe
Mayo endoscopic scoring of ulcerative colitis.
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Colon capsule endoscopy for UC San Juan-Acosta et al. 897
Patient demographics and findings of the first-generation or second-generation colon capsule endoscopy in patients with ulcerative colitis
Table 2
Age (years)a Range Sex [n (%)] Male Female Completed CCE [n (%)] Completed colonoscopy [n (%)] Completed colonoscopy and CCE [n (%)] Small bowel lesions indicative of Crohn’s disease [n (%)] Colonic cleansing (%) Excellent Good Fair Poor
C1 (N = 23)
C2 (N = 19)
Total (N = 42)
47.8 ± 12.9 26–73
49.4 ± 16.9 24–75
48.5 ± 14.7 24–75
16 7 20 20 18
(69.6) (30.4) (87.0) (87.0) (78.3)
2 (8.7)
11 8 16 17 14
(57.9) (42.1) (84.2) (89.5) (73.7)
1 (5.3)
27 15 36 37 32
(64.3) (35.7) (85.7) (88.1) (76.2)
Sensitivity (%) CCE versus colonoscopy (n = 42) Disease activity 77.78 Disease extent 68.75 C1 CCE versus colonoscopy (n = 23) Disease activity 80.00 Disease extent 75.00 C2 CCE versus colonoscopy (n = 19) Disease activity 75.00 Disease extent 62.50
Specificity (%)
PPV (%)
NPV (%)
95.83 96.15
93.33 91.67
85.19 83.33
92.31 93.33
88.89 85.71
85.71 87.50
100 100
100 100
84.62 78.57
3 (7.1) C1, first-generation CCE; C2, second-generation CCE; CCE, colon capsule endoscopy; NPV, negative predictive value; PPV, positive predictive value.
28.6 52.4 14.3 4.8
36.8 42.1 15.8 5.3
32.5 47.5 15.0 5.0
C1, first-generation CCE; C2, second-generation CCE; CCE, colon capsule endoscopy. a Mean ± SD.
lesions in 25, nine, and six patients, respectively (κ = 0.79; 95% CI: 0.62–0.96; Table 3). Similarly, slight variations between CCE and conventional colonoscopy were observed with respect to the extent of UC. During conventional colonoscopy, five, eight, and four patients were considered to have proctitis, left-side colitis, and extensive colitis, respectively, whereas four, seven, and three patients were considered to have proctitis, left-side colitis, and extensive colitis, respectively, during CCE (κ = 0.71; 95% CI: 0.52–0.90; Table 3). Data on sensitivity and specificity, as well as positive and negative predictive value, are summarized in Table 4. In the overall population, sensitivity for disease activity and extent for CCE versus colonoscopy was ∼ 78 and ∼ 69%, respectively, whereas specificity was ∼ 96% for both. Positive and negative predictive values for CCE versus colonoscopy for disease activity and extent were > 90 and > 80%, respectively. An analysis was also carried out Table 3 Correlation of the diagnostic findings of the colon capsule endoscopy and colonoscopy in patients with ulcerative colitis: severity and extent of disease
Disease severitya Inactive Mild Moderate Severe Nonconclusive Extent of UCb Inactive Proctitis (E1) Left side colitis (E2) Extensive colitis (E3) Nonconclusive
Table 4 Sensitivity, specificity, and positive and negative predictive value of colon capsule endoscopy versus colonoscopy in patients with ulcerative colitis
CCE (N = 42)
Colonoscopy (N = 42)
25 9 6 0 2
24 12 6 0 0
26 4 7 3 2
25 5 8 4 0
κ coefficient (95% CI) 0.79 (0.62, 0.96)
according to whether patients received the first-generation or second-generation PillCam (Table 4); the sensitivity for disease activity and extent for first-generation and secondgeneration devices was ≥ 75 and > 62%, respectively. Specificity was greater than 90% for the first-generation device and 100% for the second-generation device. The ability of CCE to observe small bowel mucosa allowed the diagnosis of ileocolonic Crohn’s disease to be made in three patients who had previously undergone a complete colonoscopy without ileoscopy and had biopsies consistent with UC. In one case, a large ulcer that induced an ileal stricture was observed (Fig. 2). In this patient, the PillCam was excreted after 10 days and because of this, the colonic mucosa was not explored. In the other two cases, many aphthous lesions were observed in the distal ileum (Fig. 2). Furthermore, using CCE, a case of esophagus carcinoma was diagnosed (Fig. 3). No polyps were observed with any of these two procedures. Colonic cleansing levels
Overall, bowel preparation was considered to be excellent or good in the majority of patients (Table 2). Bowel preparation was considered to be excellent in 28.6%, good in 52.4%, fair in 14.3%, and poor in one patient (4.8%) who underwent first-generation CCE evaluation and excellent in 36.8%, good in 42.1%, fair in 15.8%, and poor in 5.3% of patients who underwent secondgeneration CCE. In two patients (4.8%), it was not possible to evaluate the colon because the battery ran out in a duodenal diverticulum and intestinal stricture, respectively. Transit time of colon capsule endoscopy
0.71 (0.52, 0.90)
CCE, colon capsule endoscopy; CI, confidence interval; UC, ulcerative colitis. a Assessed by Mayo score. b Assessed by Montreal criteria.
The mean colonic transit time and the mean intestinal transit time were 118.54 ± 84.37 min (range 4.48–312.24 min) and 134 ± 117.38 min (range 51–217 min) with first-generation CCE and 156.30 ± 101.07 min (range 7.27–338.47 min) and 83.84 ± 50.74 min (range 8–208 min) with second-generation CCE, respectively. Therefore, the mean colonic transit time was 136.48 ± 93.43 min (range 4.48–338.47 min) and the mean intestinal transit time was 89.74 ± 58.24 (range
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Fig. 2
PillCam©COLON
PillCam©COLON
PillCam©COLON 2
Intestinal stenosis
PillCam©COLON
PillCam©COLON 2
Ulcers and intestinal aptha
PillCam©COLON
PillCam©COLON
PillCam©COLON
Diverticulum duodenal Cases of ileocolonic Crohn’s disease and duodenal diverticulum identified during colon capsule endoscopy.
Fig. 3
PillCam©COLON 2
PillCam©COLON 2
PillCam©COLON 2
Esophageal tumor identified during colon capsule endoscopy.
8–217 min). In addition, the overall transit after ingestion of the PillCam until excretion was 330.45 ± 118.81 min (range 121.82–579.13 min) and the excretion rate was 85.7%. Adverse events
No severe adverse events were observed. All patients could swallow the capsule. Five out of the six patients with an incomplete CCE evaluation excreted the PillCam device naturally in the 2 weeks following its ingestion and in one case it was retrieved from the splenic flexure during
colonoscopy. No other morbidities or severe adverse events related to the PillCam device or bowel preparation were reported. No patients experienced a relapse or an aggravation of their disease because of the bowel preparation. A total of 10 patients complained of mild pain related to the colonoscopy.
Discussion CCE has been proposed as an alternative to conventional colonoscopy for colorectal cancer screening [21–23] or in
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Colon capsule endoscopy for UC San Juan-Acosta et al. 899
case of incomplete colonoscopy [24] or contra-indication for colonoscopy [25,26] because it is a safe, painless, and noninvasive technique. Furthermore, it is a good tool for observation of colonic mucosa and detection of colonic lesions [16]. However, currently, there is little evidence of its beneficial use in the management of UC. In the first published report of the use of CCE in UC [17], CCE was compared with colonoscopy with the aim of evaluating its accuracy in monitoring colonic inflammation in patients with suspected or known UC. The main aim of this multicenter study was to detect active colonic mucosa inflammation; however, CCE yielded encouraging results for the detection of active UC (sensitivity 89%, specificity 75%) and showed considerable agreement with colonoscopy. Since this publication, two other studies investigating CCE for the management of UC have been published. First, Meister et al. [27] showed a significantly better assessment of disease activity with standard colonoscopy than with CCE. Furthermore, compared with colonoscopy, the extent of UC was underestimated when evaluated by CCE. In contrast, Ye et al. [18] reported a good correlation in the estimation of severity (κ = 0.751) between CCE and colonoscopy, but a moderate correlation in the estimation of the extent of the inflammation, perhaps because it is not easy to determine the precise localization of disease with CCE, and the experience of the physicians with CCE evaluation in this study was limited. However, all these studies were carried out with the firstgeneration PillCam. In contrast, this study has been carried out with both the first-generation and secondgeneration PillCam and has shown a good correlation in the evaluation of the severity and extent of disease (κ = 0.79 and 0.71; respectively) between CCE and colonoscopy (sensitivity > 68%, specificity ∼ 96%). As such, CCE appears to be a suitable technique to evaluate not only the severity of the inflammation but also the extent of UC. Of note, in this study, the severity of disease was classified using a Mayo score on the basis of its ease of use and its wide applicability in recent clinical trials of the management of UC [28]. However, in the two previous studies, the Rachmilewitz score [27] and the Baron score [18] were used. As such, a direct comparison between the studies is difficult to perform as to be able to compare results, it is necessary to use only one disease activity score. One benefit of CCE using a PillCam is its ability to evaluate the small bowel. In previous studies, it has been shown that small bowel CE is superior to small bowel radiography, computed tomography enterography, and ileocolonoscopy in the evaluation of patients with suspected Crohn’s disease [29]. In fact, in this study, the use of CCE changed the diagnosis of UC to Crohn’s disease in three patients. This is a compelling argument for the use of CCE in patients with IBD as the use of small bowel CE may be a useful diagnostic tool to change the
management in patients with IBD [30], mainly in cases of undetermined colitis [31]. The ideal bowel preparation has not yet been found; published studies have shown an overall adequate cleansing level between 35 and 90% [32]. It has been suggested that to improve the tolerability and patient compliance, a reduced volume preparation could be used, which has been reported in one study [33] and, as such, this technique was used in this study. Despite the reduced volume, the preparation for CCE (6.5 l) is still a large amount of liquid in comparison with the preparation for conventional colonoscopy (4 l PEG or 2 l PEG plus ascorbic acid), which could lead to preparation for CCE being poorer overall. However, in this study, the overall bowel cleansing level was adequate in 80% of patients, an outcome similar to previous studies [32]. This adequate cleansing allowed the analysis of almost the entire colonic mucosa. However, in this study, the excretion rate of the PillCam was only 85.7%, which is not as high as expected; in this type of study, where the rectum must be observed (the rectum is always affected in UC), it is essential that the PillCam is excreted to complete the evaluation of the bowel and validate the device. This study has several limitations. First, most patients who were included in the study were in UC remission and this study was carried out in the context of a screening program that these types of patients must participate in to rule out colorectal cancer or dysplasia. Although the selection of patients in remission who have an absence of inflammation or a mild disease activity in the colonic mucosa could be a potential bias of the study, it is well known that there is not always a good clinical–endoscopic correlation [34]. There are limitations associated with the PillCam itself that should be noted. The inability of the PillCam to take biopsies is, without doubt, a limitation of this evaluation technique; because of this, the PillCam can therefore only be used for screening for colorectal cancer lesions, not for detection of dysplasia, which requires that biopsies be taken. Also, it is important to consider that two models of CCE have been used (CCE1 and CCE2) because of the availability of only CCE1 at the beginning of the study. The large amount of liquid required for bowel preparation is a disadvantage to the procedure, as mentioned above. There are several contra-indications to the use of CCE, including swallowing disorders, previous gastrointestinal tract surgery, and bowel obstruction [32]. In patients with an implanted electromedical device such as a cardiac pacemaker, the use of CCE is not recommended (with a low level of evidence and recommendation) [32]; however, CE has been used safely in patients with implantable cardiac defibrillators [35]. Although the amount of liquid administered during CCE preparation is less than that ingested during preparation for conventional colonoscopy, the administration of
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900 European Journal of Gastroenterology & Hepatology 2014, Vol 26 No 8
sodium phosphate during the bowel preparation is also contra-indicated in some patients, including the elderly, those with baseline kidney disease or hypovolemia, bowel obstruction or active colitis, and those receiving medications affecting renal function or perfusion [32,36]. In these patients, alternative booster agents to sodium phosphate may be used for bowel preparation [32]. Cost is also a potential barrier to the use of CCE, with the procedure having direct costs of ∼ €600, versus the cost of conventional colonoscopy ( ∼ €50–100). Pharmacoeconomic analyses have shown that the cost effectiveness of CCE for colon cancer screening depends heavily on whether it improves screening compliance rates [16,36]; studies suggest that if CCE increases compliance by 30% versus conventional colonoscopy, it is a cost-effective option [37]. This suggests that it may also be a cost-effective option for screening of patients with UC who would refuse a colonoscopy or who have contra-indications to colonoscopy. Conclusion
This single-blind, prospective, comparative study shows that CCE allows an estimation of the severity and extent of known UC comparable with that obtained by a conventional colonoscopy and is a viable alternative in patients with incomplete colonoscopy or a contraindication to colonoscopy. The ability of CCE to assess the distal ileum is another advantage of the CCE because pathological findings at this level can alter the original diagnosis of UC.
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Acknowledgements The authors would like to thank Simone Boniface and Sheridan Henness, PhD, of inScience Communications, Springer Healthcare, who provided medical writing assistance. This editorial assistance was funded by Asociación Dr Marina Fiol, Spain, through funding assistance from MSD Spain.
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Conflicts of interest
There are no conflicts of interest.
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two randomized, double-blind, placebo-controlled trials. Aliment Pharmacol Ther 2007; 26:205–215. 29 Dionisio PM, Gurudu SR, Leighton JA, Leontiadis GI, Fleischer DE, Hara AK, et al. Capsule endoscopy has a significantly higher diagnostic yield in patients with suspected and established small-bowel Crohn’s disease: a meta-analysis. Am J Gastroenterol 2010; 105:1240–1248. 30 Long MD, Barnes E, Isaacs K, Morgan D, Herfarth HH. Impact of capsule endoscopy on management of inflammatory bowel disease: a single tertiary care center experience. Inflamm Bowel Dis 2011; 17:1855–1862. 31 Maunoury V, Savoye G, Bourreille A, Bouhnik Y, Jarry M, SacherHuvelin S, et al. Value of wireless capsule endoscopy in patients with indeterminate colitis (inflammatory bowel disease type unclassified). Inflamm Bowel Dis 2007; 13:152–155. 32 Spada C, Hassan C, Galmiche JP, Neuhaus H, Dumonceau JM, Adler S, et al. Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2012; 44:527–536. 33 Hartmann D, Keuchel M, Philipper M, Gralnek IM, Jakobs R, Hagenmuller F, et al. A pilot study evaluating a new low-volume colon
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Original article
Colon capsule endoscopy is a safe and useful tool to assess disease parameters in patients with ulcerative colitis Mileidis San Juan-Acosta, Angel Caunedo-Álvarez, Federico Argüelles-Arias, Luisa Castro-Laria, Blas Gómez-Rodríguez, Javier Romero-Vázquez, Alba Belda-Cuesta, Francisco Pellicer-Bautista and Juan M. Herrerías-Gutiérrez Objective Colon capsule endoscopy (CCE) is a new endoscopic technique that is minimally invasive and allows evaluation of the colon mucosa without pain, sedation, and gas insufflation. To date, few studies have investigated the use of CCE in patients with ulcerative colitis (UC). This study compares the ability of CCE and a conventional colonoscopy to assess mucosal disease activity and the extent of inflammatory mucosa in patients with UC. Methods Forty-two patients (27 men, mean age 48.5 years) with known UC and indication for colonoscopy were enrolled in this single-blind, prospective study. All patients underwent CCE, followed by a colonoscopy. The activity and extent of the disease was assessed using Mayo scores and Montreal scores, respectively. Results There was a good correlation between CCE and colonoscopy in disease severity (κ = 0.79; 95% confidence interval: 0.62–0.96) and extent of inflammation (κ = 0.71; 95% confidence interval: 0.52–0.90) observed. The ability of CCE to assess a broad segment of distal ileum led to a change in the diagnosis of UC to ileocolonic Crohn’s
Introduction Ulcerative colitis (UC) is a chronic inflammatory condition that causes continuous mucosal inflammation of the colon, without granulomas on biopsy, and is characterized by a relapsing and remitting course [1]. It affects the rectum and a variable extent of the colon in continuity and its symptoms most commonly include bloody diarrhea, rectal bleeding, or rectal urgency [2,3]. The severity of these symptoms is usually related to the extent of mucosal inflammation and can be observed by colonoscopy [2,3]. The use of a colonoscopy establishes the diagnosis and extent of disease in the majority of UC cases and it is the gold standard for diagnosis and to determine the extent of UC and monitor mucosal status [4]. Visualization of the mucosa affected in UC is essential for many aspects of disease management (including drug dosing and duration, the use of oral and/ or topical treatment, and the decision to deliver intravenous medication or undergo surgery) and can predict recurrence rates and complications related to UC (such as hospitalizations, the need for surgery, or an increase/ change in treatment) according to the degree of mucosal healing [5]. Endoscopic features of mild inflammation are 0954-691X © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
disease in three patients. Bowel preparation was considered adequate in 80% of the patients and no serious adverse events related to the CCE procedure or bowel preparation were reported. Conclusion CCE is a safe and useful method for the evaluation of patients with UC. The ability of CCE to assess distal ileum provides an advantage to colonoscopy as CCE can identify patients who have been incorrectly diagnosed with UC, resulting in a change in their diagnosis to Crohn’s disease. Eur J Gastroenterol Hepatol 26:894–901 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. European Journal of Gastroenterology & Hepatology 2014, 26:894–901 Keywords: colon capsule endoscopy, colonoscopy, PillCam, ulcerative colitis Virgen Macarena Hospital, Sevilla, Spain Correspondence to Federico Argüelles-Arias, PhD, Virgen Macarena Hospital, Dr Fedriani s/n, 41071 Sevilla, Spain Tel: + 34 955 00 88 01; fax: + 34 955 00 88 05; e-mail: [email protected] Received 26 December 2013 Accepted 15 April 2014
erythema, loss of visible vascular pattern, and vascular congestion of the mucosa; moderately active colitis is characterized by complete loss of vascular pattern, with a coarse granular appearance and mucosal friability, blood adherent to the surface of the mucosa and erosions; and severe colitis is characterized by spontaneous bleeding and ulceration [6]. Patients with UC have an increased risk of developing colon cancer, which can been attributed to two factors: the length of time since disease onset and the extent of colon affected by UC [7]. According to a meta-analysis of 116 colorectal cancer studies, the overall prevalence of colorectal cancer among UC patients is 3.7% [95% confidence interval (CI) 3.2–4.2], with incidence rates corresponding to cumulative probabilities of 2% at 10 years, 8% at 20 years, and 18% at 30 years [8]. As such, it is recommended in patients who have had UC for 8–10 years (or 15 years of disease in patients with left-sided colitis) that annual or biannual surveillance colonoscopy with multiple biopsies at regular intervals are performed to detect and avoid colorectal cancer [9–12]. DOI: 10.1097/MEG.0000000000000125
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Colon capsule endoscopy for UC San Juan-Acosta et al. 895
A colonoscopy is one of the main tools used to manage patients with UC as it can assess the diagnosis of UC, the extent of inflammation, and a patient’s response to drugs, and it can be used for colorectal cancer screening; however, a colonoscopy is an invasive and uncomfortable procedure in some patients. Colon capsule endoscopy (CCE) is a new endoscopic technique that represents a minimally invasive imaging system that allows exploration of the colon mucosa without pain, sedation, and gas insufflation. CCE has been used for the screening of colorectal cancer [13–15] and appears to be a promising new modality for colonic evaluation [16]. Furthermore, CCE may be useful for the evaluation of colonic lesions and it could be a good alternative for patients refusing conventional colonoscopy or when it is contra-indicated. To date, a few preliminary studies have shown the feasibility of CCE for the management of patients with known UC [17,18], suggesting that CCE may be useful for monitoring inflammation and screening for colorectal cancer in patients with UC. The aim of this study was to compare the use of CCE with standard colonoscopy in the assessment of mucosal disease activity and extent of inflammatory mucosa in patients with UC.
Bowel preparation and time course of evaluations
An overview of the bowel preparation technique utilized in this study is presented in Table 1. Two days before the examination, patients began a low-residue diet and received 48 mg oral sennosides before bedtime. The following day, patients underwent a clear-liquid diet and drank a 2-l PEG bowel preparation at night. On the day of the examination, patients were to have fasted at least overnight (12 h) and were administered a 2-l PEG solution at 7:00 a.m. A PillCam colon capsule was swallowed by the patient with 20 mg domperidone at 9:00 am. An hour and a half later, RAPID software (Given Imaging Ltd, Yokneam, Israel) was used to verify that the PillCam had moved out of the stomach and then a booster of oral sodium phosphate solution (30 ml) was administered. Three hours later, a second booster of oral sodium phosphate solution was administered to promote distal movement of the PillCam through the bowel and excretion. Bisacodyl suppository was administered only if the capsule was not excreted. The CCE was considered ‘complete’ when the hemorrhoidal plexus was identified. After this, on the same day of the CCE procedure, a standard colonoscopy was performed (Table 1). Colon capsule endoscopy
Methods Patients
This single-blind, prospective, comparative study was carried out at the Virgen Macarena University Hospital in Seville, Spain, from January 2010 to January 2012. Patients aged 18–70 years with UC were enrolled if they had either a suspected flare in disease activity or were due to undergo screening for colorectal cancer. Patients were excluded if they had (a) dysphagia, (b) intestinal strictures (confirmed or suspected), (c) high risk of capsule retention (Crohn’s disease, small bowel tumor, radiation enteropathy, previous intestinal surgery), (d) serious systemic diseases such as heart failure, renal insufficiency, defibrillators, or cardiac pace makers, (e) were allergic or intolerant to sodium phosphate, polyethylene glycol (PEG) solution, domperidone, or bisacodyl suppository, or were (f) pregnant.
Two models of PillCam colon capsule (Given Imaging Ltd) were used in this study. The firstgeneration device measures 31 × 11 mm, acquires images at a rate of 4 frames/s, and has a ‘sleep mode’ of 1 h 45 min, during which the capsule is supposed to travel through the stomach (thus saving energy). The secondgeneration device measures 31.5 × 11.6 mm and has two imagers, one at each end of the capsule. In this device, the angle of view is increased to 172° and to conserve battery energy, the capsule captures images at an adaptive frame rate, alternating from 35 images/s while it is in motion (such as in the transverse colon) to 4 images/s when it is virtually stationary. After swallowing, the capsule works at a low frame rate of 14 images/min until it identifies the small bowel. The new data recorder also assists and guides the medical staff and patient through the procedure. It buzzes, vibrates, and displays Table 1
Written informed consent was obtained from each patient before the two procedures. The study protocol conformed to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Virgen Macarena Hospital.
Bowel preparation
Day
Time
Procedure
−2
All day 19:00–21:00 All day 19:00–21:00 06:00–08:30 09:00 09:00 10:30 13:30 15:00 16:30 19:00
Low-residue diet 48 mg sennosides Liquid diet only 2 l PEG 2 l PEG PillCam ingestion Domperidone (20 mg) 30 ml NaP + 1.5 l water 25 ml NaP + 1 l water Snack (optional) 10 mg suppository bisacodyl Standard colonoscopy
−1 0 (exam day)
Methods of evaluation
All patients underwent CCE and then received a conventional colonoscopy. The extent of mucosal disease activity and inflammatory mucosa during both procedures was recorded for comparison.
NaP, sodium phosphate; PEG, polyethylene glycol.
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instruction numbers to alert the patient to take the laxative booster or that the procedure has terminated. Videos were analyzed using the RAPID software (RAPID 6.0 for CCE1 and RAPID 7.0 for CCE2) by an expert physician in capsule endoscopy (CE) who was blinded to the colonoscopy results and also blinded to the patient’s illness characteristics. Conventional colonoscopy
Conventional colonoscopy (CF-H180 Al; Olympus, Tokyo, Japan) was performed by a physician blinded to the results of the CCE and to the patient’s characteristics. Patients were administered intravenous midazolam (2–5 mg) to attain conscious sedation. All investigators were gastroenterologists with experience in colonoscopy and CCE. Assessments
The extent of mucosal disease activity and inflammatory mucosa was assessed during both the CCE and colonoscopy. To diagnose the extent of disease, lesions were classified as ulcerative proctitis (E1), left-side UC (E2), or extensive UC (E3), on the basis of the 2005 Montreal classification of inflammatory bowel disease (IBD) criteria, which were originally presented at the 2005 World Congress of Gastroenterology [1]. The endoscopic activity of UC was classified using a Mayo score (Fig. 1) that defined UC as either mild, moderate, or severe [19]. Colonic cleansing was also assessed using the Leighton scale [20], which defined response as excellent, good, fair, and poor. Finally, the safety of both processes and the preparation of the bowel were also assessed.
and extent between the endoscopists were assessed using Cohen’s κ coefficient.
Results A total of 47 patients were enrolled in the study. Of these, two patients refused conventional colonoscopy after inclusion, one patient refused CCE, and in two patients, the PillCam capsule never transmitted images after ingestion, leading to technical failure of the CCE. Therefore, 42 patients (15 women/27 men), mean age 48.5 years (range 24–75 years), were included in the analysis. Of these, 23 patients underwent a first-generation CCE and 19 patients underwent a second-generation CCE (Table 2). Feasibility of first-generation and second-generation colon capsule endoscopy
Overall, 85.7% of patients who underwent CCE monitoring completed the evaluation (Table 2). In the group of patients who underwent CCE with a first-generation device, a complete evaluation of the colon was possible in 20 patients (87.0%). Reasons for an incomplete examination were the battery running out of power in the rectum (two patients) and the capsule staying in a duodenal diverticulum (one patient). In this case, colonic mucosa was not seen. In the group of patients who underwent CCE with a second-generation device, a complete evaluation of the colon was possible in 16 patients (84.2%). The causes of incomplete examination were the battery running out of power in the splenic flexure (two patients) and the capsule stopping in a stricture in the terminal ileum (one patient). In this case, colonic mucosa was not seen.
Statistical analysis
Correlation between colon capsule endoscopy and conventional colonoscopy
Statistical analysis was carried out using SPSS (SPSS 17.0; SPSS Inc., Chicago, Illinois, USA). Results were expressed as mean ± SD with minimum and maximum values, and categorical data were expressed as percentage. Differences in the recognition of disease activity
The apparent severity of UC varied between the two evaluations. During the conventional colonoscopy, quiescent (inactive), mild, and moderate disease activity was observed in 24, 12, and six patients, respectively; in contrast, the CCE showed quiescent, mild, and moderate
Fig. 1 ∗ 4309
∗
11908
∗ 4426
∗ 11480
D. F:8 Ex:1 α:N
Conectado a ENDOBASE
Conectado a ENDOBASE
Normal
Mild
Conectado a ENDOBASE
Moderate
Conectado a ENDOBASE
Severe
Mayo endoscopic scoring of ulcerative colitis.
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Patient demographics and findings of the first-generation or second-generation colon capsule endoscopy in patients with ulcerative colitis
Table 2
Age (years)a Range Sex [n (%)] Male Female Completed CCE [n (%)] Completed colonoscopy [n (%)] Completed colonoscopy and CCE [n (%)] Small bowel lesions indicative of Crohn’s disease [n (%)] Colonic cleansing (%) Excellent Good Fair Poor
C1 (N = 23)
C2 (N = 19)
Total (N = 42)
47.8 ± 12.9 26–73
49.4 ± 16.9 24–75
48.5 ± 14.7 24–75
16 7 20 20 18
(69.6) (30.4) (87.0) (87.0) (78.3)
2 (8.7)
11 8 16 17 14
(57.9) (42.1) (84.2) (89.5) (73.7)
1 (5.3)
27 15 36 37 32
(64.3) (35.7) (85.7) (88.1) (76.2)
Sensitivity (%) CCE versus colonoscopy (n = 42) Disease activity 77.78 Disease extent 68.75 C1 CCE versus colonoscopy (n = 23) Disease activity 80.00 Disease extent 75.00 C2 CCE versus colonoscopy (n = 19) Disease activity 75.00 Disease extent 62.50
Specificity (%)
PPV (%)
NPV (%)
95.83 96.15
93.33 91.67
85.19 83.33
92.31 93.33
88.89 85.71
85.71 87.50
100 100
100 100
84.62 78.57
3 (7.1) C1, first-generation CCE; C2, second-generation CCE; CCE, colon capsule endoscopy; NPV, negative predictive value; PPV, positive predictive value.
28.6 52.4 14.3 4.8
36.8 42.1 15.8 5.3
32.5 47.5 15.0 5.0
C1, first-generation CCE; C2, second-generation CCE; CCE, colon capsule endoscopy. a Mean ± SD.
lesions in 25, nine, and six patients, respectively (κ = 0.79; 95% CI: 0.62–0.96; Table 3). Similarly, slight variations between CCE and conventional colonoscopy were observed with respect to the extent of UC. During conventional colonoscopy, five, eight, and four patients were considered to have proctitis, left-side colitis, and extensive colitis, respectively, whereas four, seven, and three patients were considered to have proctitis, left-side colitis, and extensive colitis, respectively, during CCE (κ = 0.71; 95% CI: 0.52–0.90; Table 3). Data on sensitivity and specificity, as well as positive and negative predictive value, are summarized in Table 4. In the overall population, sensitivity for disease activity and extent for CCE versus colonoscopy was ∼ 78 and ∼ 69%, respectively, whereas specificity was ∼ 96% for both. Positive and negative predictive values for CCE versus colonoscopy for disease activity and extent were > 90 and > 80%, respectively. An analysis was also carried out Table 3 Correlation of the diagnostic findings of the colon capsule endoscopy and colonoscopy in patients with ulcerative colitis: severity and extent of disease
Disease severitya Inactive Mild Moderate Severe Nonconclusive Extent of UCb Inactive Proctitis (E1) Left side colitis (E2) Extensive colitis (E3) Nonconclusive
Table 4 Sensitivity, specificity, and positive and negative predictive value of colon capsule endoscopy versus colonoscopy in patients with ulcerative colitis
CCE (N = 42)
Colonoscopy (N = 42)
25 9 6 0 2
24 12 6 0 0
26 4 7 3 2
25 5 8 4 0
κ coefficient (95% CI) 0.79 (0.62, 0.96)
according to whether patients received the first-generation or second-generation PillCam (Table 4); the sensitivity for disease activity and extent for first-generation and secondgeneration devices was ≥ 75 and > 62%, respectively. Specificity was greater than 90% for the first-generation device and 100% for the second-generation device. The ability of CCE to observe small bowel mucosa allowed the diagnosis of ileocolonic Crohn’s disease to be made in three patients who had previously undergone a complete colonoscopy without ileoscopy and had biopsies consistent with UC. In one case, a large ulcer that induced an ileal stricture was observed (Fig. 2). In this patient, the PillCam was excreted after 10 days and because of this, the colonic mucosa was not explored. In the other two cases, many aphthous lesions were observed in the distal ileum (Fig. 2). Furthermore, using CCE, a case of esophagus carcinoma was diagnosed (Fig. 3). No polyps were observed with any of these two procedures. Colonic cleansing levels
Overall, bowel preparation was considered to be excellent or good in the majority of patients (Table 2). Bowel preparation was considered to be excellent in 28.6%, good in 52.4%, fair in 14.3%, and poor in one patient (4.8%) who underwent first-generation CCE evaluation and excellent in 36.8%, good in 42.1%, fair in 15.8%, and poor in 5.3% of patients who underwent secondgeneration CCE. In two patients (4.8%), it was not possible to evaluate the colon because the battery ran out in a duodenal diverticulum and intestinal stricture, respectively. Transit time of colon capsule endoscopy
0.71 (0.52, 0.90)
CCE, colon capsule endoscopy; CI, confidence interval; UC, ulcerative colitis. a Assessed by Mayo score. b Assessed by Montreal criteria.
The mean colonic transit time and the mean intestinal transit time were 118.54 ± 84.37 min (range 4.48–312.24 min) and 134 ± 117.38 min (range 51–217 min) with first-generation CCE and 156.30 ± 101.07 min (range 7.27–338.47 min) and 83.84 ± 50.74 min (range 8–208 min) with second-generation CCE, respectively. Therefore, the mean colonic transit time was 136.48 ± 93.43 min (range 4.48–338.47 min) and the mean intestinal transit time was 89.74 ± 58.24 (range
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Fig. 2
PillCam©COLON
PillCam©COLON
PillCam©COLON 2
Intestinal stenosis
PillCam©COLON
PillCam©COLON 2
Ulcers and intestinal aptha
PillCam©COLON
PillCam©COLON
PillCam©COLON
Diverticulum duodenal Cases of ileocolonic Crohn’s disease and duodenal diverticulum identified during colon capsule endoscopy.
Fig. 3
PillCam©COLON 2
PillCam©COLON 2
PillCam©COLON 2
Esophageal tumor identified during colon capsule endoscopy.
8–217 min). In addition, the overall transit after ingestion of the PillCam until excretion was 330.45 ± 118.81 min (range 121.82–579.13 min) and the excretion rate was 85.7%. Adverse events
No severe adverse events were observed. All patients could swallow the capsule. Five out of the six patients with an incomplete CCE evaluation excreted the PillCam device naturally in the 2 weeks following its ingestion and in one case it was retrieved from the splenic flexure during
colonoscopy. No other morbidities or severe adverse events related to the PillCam device or bowel preparation were reported. No patients experienced a relapse or an aggravation of their disease because of the bowel preparation. A total of 10 patients complained of mild pain related to the colonoscopy.
Discussion CCE has been proposed as an alternative to conventional colonoscopy for colorectal cancer screening [21–23] or in
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case of incomplete colonoscopy [24] or contra-indication for colonoscopy [25,26] because it is a safe, painless, and noninvasive technique. Furthermore, it is a good tool for observation of colonic mucosa and detection of colonic lesions [16]. However, currently, there is little evidence of its beneficial use in the management of UC. In the first published report of the use of CCE in UC [17], CCE was compared with colonoscopy with the aim of evaluating its accuracy in monitoring colonic inflammation in patients with suspected or known UC. The main aim of this multicenter study was to detect active colonic mucosa inflammation; however, CCE yielded encouraging results for the detection of active UC (sensitivity 89%, specificity 75%) and showed considerable agreement with colonoscopy. Since this publication, two other studies investigating CCE for the management of UC have been published. First, Meister et al. [27] showed a significantly better assessment of disease activity with standard colonoscopy than with CCE. Furthermore, compared with colonoscopy, the extent of UC was underestimated when evaluated by CCE. In contrast, Ye et al. [18] reported a good correlation in the estimation of severity (κ = 0.751) between CCE and colonoscopy, but a moderate correlation in the estimation of the extent of the inflammation, perhaps because it is not easy to determine the precise localization of disease with CCE, and the experience of the physicians with CCE evaluation in this study was limited. However, all these studies were carried out with the firstgeneration PillCam. In contrast, this study has been carried out with both the first-generation and secondgeneration PillCam and has shown a good correlation in the evaluation of the severity and extent of disease (κ = 0.79 and 0.71; respectively) between CCE and colonoscopy (sensitivity > 68%, specificity ∼ 96%). As such, CCE appears to be a suitable technique to evaluate not only the severity of the inflammation but also the extent of UC. Of note, in this study, the severity of disease was classified using a Mayo score on the basis of its ease of use and its wide applicability in recent clinical trials of the management of UC [28]. However, in the two previous studies, the Rachmilewitz score [27] and the Baron score [18] were used. As such, a direct comparison between the studies is difficult to perform as to be able to compare results, it is necessary to use only one disease activity score. One benefit of CCE using a PillCam is its ability to evaluate the small bowel. In previous studies, it has been shown that small bowel CE is superior to small bowel radiography, computed tomography enterography, and ileocolonoscopy in the evaluation of patients with suspected Crohn’s disease [29]. In fact, in this study, the use of CCE changed the diagnosis of UC to Crohn’s disease in three patients. This is a compelling argument for the use of CCE in patients with IBD as the use of small bowel CE may be a useful diagnostic tool to change the
management in patients with IBD [30], mainly in cases of undetermined colitis [31]. The ideal bowel preparation has not yet been found; published studies have shown an overall adequate cleansing level between 35 and 90% [32]. It has been suggested that to improve the tolerability and patient compliance, a reduced volume preparation could be used, which has been reported in one study [33] and, as such, this technique was used in this study. Despite the reduced volume, the preparation for CCE (6.5 l) is still a large amount of liquid in comparison with the preparation for conventional colonoscopy (4 l PEG or 2 l PEG plus ascorbic acid), which could lead to preparation for CCE being poorer overall. However, in this study, the overall bowel cleansing level was adequate in 80% of patients, an outcome similar to previous studies [32]. This adequate cleansing allowed the analysis of almost the entire colonic mucosa. However, in this study, the excretion rate of the PillCam was only 85.7%, which is not as high as expected; in this type of study, where the rectum must be observed (the rectum is always affected in UC), it is essential that the PillCam is excreted to complete the evaluation of the bowel and validate the device. This study has several limitations. First, most patients who were included in the study were in UC remission and this study was carried out in the context of a screening program that these types of patients must participate in to rule out colorectal cancer or dysplasia. Although the selection of patients in remission who have an absence of inflammation or a mild disease activity in the colonic mucosa could be a potential bias of the study, it is well known that there is not always a good clinical–endoscopic correlation [34]. There are limitations associated with the PillCam itself that should be noted. The inability of the PillCam to take biopsies is, without doubt, a limitation of this evaluation technique; because of this, the PillCam can therefore only be used for screening for colorectal cancer lesions, not for detection of dysplasia, which requires that biopsies be taken. Also, it is important to consider that two models of CCE have been used (CCE1 and CCE2) because of the availability of only CCE1 at the beginning of the study. The large amount of liquid required for bowel preparation is a disadvantage to the procedure, as mentioned above. There are several contra-indications to the use of CCE, including swallowing disorders, previous gastrointestinal tract surgery, and bowel obstruction [32]. In patients with an implanted electromedical device such as a cardiac pacemaker, the use of CCE is not recommended (with a low level of evidence and recommendation) [32]; however, CE has been used safely in patients with implantable cardiac defibrillators [35]. Although the amount of liquid administered during CCE preparation is less than that ingested during preparation for conventional colonoscopy, the administration of
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900 European Journal of Gastroenterology & Hepatology 2014, Vol 26 No 8
sodium phosphate during the bowel preparation is also contra-indicated in some patients, including the elderly, those with baseline kidney disease or hypovolemia, bowel obstruction or active colitis, and those receiving medications affecting renal function or perfusion [32,36]. In these patients, alternative booster agents to sodium phosphate may be used for bowel preparation [32]. Cost is also a potential barrier to the use of CCE, with the procedure having direct costs of ∼ €600, versus the cost of conventional colonoscopy ( ∼ €50–100). Pharmacoeconomic analyses have shown that the cost effectiveness of CCE for colon cancer screening depends heavily on whether it improves screening compliance rates [16,36]; studies suggest that if CCE increases compliance by 30% versus conventional colonoscopy, it is a cost-effective option [37]. This suggests that it may also be a cost-effective option for screening of patients with UC who would refuse a colonoscopy or who have contra-indications to colonoscopy. Conclusion
This single-blind, prospective, comparative study shows that CCE allows an estimation of the severity and extent of known UC comparable with that obtained by a conventional colonoscopy and is a viable alternative in patients with incomplete colonoscopy or a contraindication to colonoscopy. The ability of CCE to assess the distal ileum is another advantage of the CCE because pathological findings at this level can alter the original diagnosis of UC.
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Acknowledgements The authors would like to thank Simone Boniface and Sheridan Henness, PhD, of inScience Communications, Springer Healthcare, who provided medical writing assistance. This editorial assistance was funded by Asociación Dr Marina Fiol, Spain, through funding assistance from MSD Spain.
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Conflicts of interest
There are no conflicts of interest.
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