Bowel preparation in "real-life" small bowel capsule endoscopy: a two-center experience.

BACKGROUND: Video capsule endoscopy (VCE) is an established diagnostic tool for the investigation of small bowel (SB) pathology. Bowel preparation prior to VCE may improve visualization, transit time, and diagnostic yield. We aimed to evaluate the "real-life" experience comparing two different preparation protocols in patients undergoing SB VCE.
METHODS: We performed a retrospective analysis of prospectively collected data from SB VCE procedures, performed in two tertiary care medical centers in Israel. VCE procedures performed at "Sheba Medical Center" used a 2-L polyethylene glycol (PEG) bowel preparation (n=360) while VCEs performed at "Rambam Health Care campus" used a clear liquid diet plus 12-h fast protocol (n=500). A dichotomous preparation scale (adequate, inadequate) was used to classify cleansing quality. Data collection included patient and procedural details. The proportion of VCE procedures with adequate bowel preparation and the overall positive SB findings in the two different bowel preparation protocols were evaluated.
RESULTS: SB completion rates were higher in the PEG protocol (96% vs. 83%, P<0.001) and SB passage time was significantly faster in the PEG protocol (mean 217±73 vs. 238±77 min, P<0.001). Bowel preparation quality was similar between groups (8% vs. 7% inadequate preparation, P=0.591). Overall positive SB findings were similar between the two groups (57% clear liquid fasting only vs. 51% PEG protocol, P=0.119).
CONCLUSION: In this large cohort, a 2-L PEG protocol had similar preparation quality and diagnostic yield compared with clear liquid fasting.

Introduction

During the past decade, video capsule endoscopy (VCE) has emerged as a clinically useful and patient-friendly diagnostic tool for the investigation of obscure gastrointestinal bleeding/iron deficiency anemia, suspected small bowel (SB) Crohn’s disease, and SB polyposis syndromes/tumors. Overall, VCE provides a definitive diagnosis in approximately 50% of cases [1-7]. Furthermore, VCE has also been shown to have a superior diagnostic yield (DY) compared to the other imaging modalities for the diagnosis of SB lesions [8-16].

The DY of VCE can be impaired by the presence of turbid intestinal contents and/or air bubbles. Bowel preparation performed prior to VCE may improve visualization and lead to a more successful VCE examination. Bowel preparation recommended by the capsule manufacturers is an 8-12-h clear liquids diet only. Some studies have found that the use of purgatives prior to capsule ingestion may result in higher quality images and DY [17-22], whereas others have failed to confirm these observations [23-26]. Thus, there is a lack of consensus regarding the role of bowel preparation prior to SB VCE. Among the polyethylene glycol (PEG)-based laxatives, a low-volume preparation has been shown to be at least equally effective when compared to high-volume regimens [21,27,28]. Therefore, a 2-L PEG-based preparation, administered the day before the VCE procedure, is an accepted practice. The aim of this study was to evaluate the effectiveness of two alternative bowel preparations in patients undergoing SB VCE.

Materials and methods

We retrospectively analyzed prospectively collected data from n=860 SB VCE procedures performed in two tertiary care medical centers in Israel (Rambam Health Care Campus, Haifa and Sheba Medical Center, Tel Hashomer). Data collection included patient demographics, VCE indication, capsule technical information including transition times between bowel segments, bowel preparation type and quality of preparation, and findings of the VCE examination.

We included all adult patients (age ≥18) referred to our centers for VCE between January 1, 2001 and December 31, 2012, for whom we had knowledge of the bowel cleansing protocol used. All VCE procedures, in both centers throughout the study period, were performed using the GIVEN Imaging video capsule (SB1 or SB2 capsule platforms) and RAPID VCE software (GIVEN Imaging/COVIDIEN Ltd).

VCE procedures performed at Sheba Medical Center used a 2-L PEG-based bowel preparation given the evening before the VCE procedure. The VCE procedures performed at Rambam Health Care Campus used only a clear liquid diet the day prior to VCE plus a 12-h fasting protocol prior to VCE ingestion. A dichotomous preparation scale (adequate or inadequate) was used to grade the quality of SB cleansing as designated by the reader of the study. In both centers, it was standard practice to explicitly document inadequate preparation quality in the VCE report. If no such documentation was made, or no recommendation for repeat VCE was made, bowel preparation quality was deemed to be adequate.

VCE reports routinely included documentation of anatomical landmarks identified such as “first gastric image”, “first duodenal image” and “first cecal image”. The gastric passage time was calculated as the elapsed time between the first gastric image and the first duodenal image. SB transit time was calculated as the elapsed time from the first duodenal image to the first cecal image. SB completion was defined as the capsule seen in the cecum.

At Rambam Health Care Campus, termination of a VCE procedure is based on the interpretation of the RAPID VIEWER after 6-7 h. At Sheba Medical Center, patients routinely continue the VCE procedure until the capsule’s battery life is exhausted. The study was approved by the institutional review board (IRB code 0084-13-RMB). Data was analyzed as groups and individual patient consent was not sought as per IRB approval.

Statistical analysis

This was a retrospective study, therefore no statistical power calculations were performed a priori. Summary statistics (arithmetic mean, standard deviation and frequency) are presented for quantitative variables. Pearson’s χ2 test was used to evaluate differences between the two bowel preparation groups (i.e., 2 L PEG vs. clear liquid fasting only) for the detection of lesions in the SB. All applied tests were two-tailed with a significance assigned at 0.05. We analyzed the data using SPSS version 21.

Results

Eight hundred and sixty VCE procedures were evaluated (Rambam Health Care Campus n=500 and Sheba Medical Center n=360). Patient demographics, including gender and weight were similar between the two centers (P=0.40, P=0.80 respectively), however the mean patient age of the patients receiving PEG preparation was significantly older (52.6 years ± 19 vs. 48.4 years ±21 P=0.018), (Table 1). Indications for VCE included obscure gastrointestinal bleeding (14%), iron deficiency anemia (40%), and suspected Crohn’s disease (40%). Other indications (weight loss, abdominal pain, diarrhea, refractory celiac disease, polyposis syndromes) accounted for 6% of referrals. There was significant heterogeneity between the centers in the distribution of the various indications within each study site (Table 2).

Table 1

Clinical characteristics of patients that received a clear liquid fasting and PEG-based preparation for capsule endoscopy

Table 2

Indications for capsule endoscopy stratified by preparation regimens

Gastric passage time was not significantly different between the two protocols (mean 25.0±21 min for clear liquid fasting vs. 22.7±21 min for PEG, P=0.077). However, SB passage time was significantly faster for the cohort receiving PEG (217±73 min vs. 238±77 min P<0.001). SB completion rates were also significantly higher in the PEG-receiving group (96% vs. 83%, P<0.001). The percentage of adequate SB preparation did not differ significantly between the groups (92% vs. 93% adequate cleansing in the clear liquid fasting and PEG groups respectively, (P=0.59). Finally, no significant difference in overall positive SB findings between the two preparation protocols was observed (57% clear liquid fasting only vs. 51% PEG, P=0.12), (Table 3).

Table 3

Procedure characteristics and outcomes stratified by preparation regimen

Capsule endoscopy was performed for suspected Crohn’s disease in 288/860, 33.5% of the patients. In these patients, the prevalence of relevant diagnostic findings (mucosal ulcers/erosions) was higher in patients prepared with clear diet (27.4% vs. 13.2%, P=0.03).

Discussion

In this retrospective study, we evaluated “real-life” experience with two different SB preparation protocols. We found no significant difference in the gastric passage time between the two protocols; however, we found a significantly shorter SB passage time and a higher SB completion rate in the cohort who received PEG. From our clinical experience, incomplete procedures are usually due to premature disconnection of the VCE recorder when content seen on the RAPID VIEWER significantly obscures the lumen and is mistaken for colonic content. In our study, the observed differences in capsule completion rates between the two centers are most probably attributable to the difference in the definition of study completion between the two centers, suggesting that the use of the rapid viewer as the lone standard for determining SB completion may not be appropriate. Importantly, with the introduction of new generation capsules such as SBIII with a battery time of approximately 12 h, the rate of capsule completion increased significantly. Theoretically, differences in completion rates may influence DY. In this study, the completion rate was higher for the PEG protocol, but this did not translate into a higher DY. Incomplete procedures in the clear liquid fasting protocol were due to “colon-like” luminal content seen on the RAPID viewer. In such cases, where adequate mucosal visibility cannot be obtained, the impact of early disconnection on DY is most likely marginal.

There were no significant differences between the two preparation protocols in regards to overall SB capsule findings (57% clear liquid fasting only vs. 51% PEG, P=0.12). In the 2-L PEG cleansing protocol, 93% of the procedures were considered to have had adequate preparation compared with 92% of the procedures in the clear liquid fasting only protocol (P=0.59). In a meta-analysis by Rokkas et al [18], data from 476 patients directly comparing different preparation protocols was analyzed. A significant benefit was demonstrated for those patients who received purgatives (for DY - OR 1.81, 95%CI 1.25-2.63, P=0.002) and for SB visualization quality (SBVQ) - OR 2.113, 95%CI 1.25-3.57, P=0.005). An additional meta-analysis by Belsey et al [21] evaluating 8 studies with 850 patients, concluded that compared with fasting alone, the use of any form of bowel preparation prior to VCE ingestion yielded significantly better visibility and DYs, (OR 2.31, 95%CI 1.46-3.63, P<0.0001 and OR 1.88, 95%CI 1.24-2.84, P<0.023 respectively). When per-treatment, post-hoc analysis was performed, only the PEG-based regimens demonstrated a benefit in DY (OR 3.11, 95%CI 1.96-4.94, P<0.0001). In 2009, the European Society for Gastrointestinal Endoscopy (ESGE) issued clinical recommendations on the use of VCE to investigate SB, esophageal and colonic diseases [28]. These guidelines state that a purgative bowel preparation given prior to VCE ingestion enhances the DY of SB VCE, but does not affect the SB capsule completion rate. However, there is no consensus or specific recommendation on the most appropriate type of bowel preparation. Finally, Vliegen et al [29], concluded that the use of a PEG-based regimen as preparation for VCE is recommended as first-line (level of evidence - Grade A). Our study did not employ a validated cleansing score for VCE. However, currently such score does not exist. Park et al [23] used a four-step scale based on the proportion of SB mucosa visualized and the extent of obscured visualization due to bubbles and turbid bowel content. Other studies [17,25,26,30] used a semi-objective two-step score based on the percentage of obscured SB mucosa. In a study by Van Tuyl et al [27], SB visualization of less than 75% was considered poor whereas visualization of more than 75% was considered good. In a meta-analysis by Rokkas et al [18], a significant heterogeneity in the visualization scores was demonstrated between the studies evaluated. Finally, a recent consensus guideline [29] concluded that validated scales for quality of cleansing are not yet available. Instead, we use a “real-life” practical definition on the assessment of the preparation appropriateness by the study reader.

Our study has additional limitations. As described before, our two populations were heterogeneous and differed in several baseline characteristics such as mean age and distribution of the various indications for VCE within the cohort. While this undoubtedly presents a bias in this study, we believe that the clinical significance of these differences are minor and the size of the cohort enables us to draw conclusions regarding the primary study endpoint, which was to assess whether in a real-life setting, bowel preparation type influences bowel visualization and VCE DY.

We did not have access to the detailed patient files and some of the indications listed can in fact be generalized into broader categories; e.g., a patient referred for chronic diarrhea and weight loss can also be regarded as a “suspected Crohn’s disease” indication. In addition, some of the patients had more than one indication specified; e.g., anemia and diarrhea, which can both be grouped into the “suspected Crohn’s disease” indication or be viewed as two separate indications possibly stemming from two different pathological entities. This made the categorization process somewhat variable. However, we are not aware of any published literature suggesting that VCE procedure indication may influence bowel preparation, DY or transit time and therefore we believe that this observed heterogeneity between the two cohorts should not have interfered with the measured outcomes. Interestingly, the percentage of positive findings was lower in patients receiving PEG preparation if the indication for the test was suspected Crohn’s disease. We do not have a good explanation for this result, however, it may further emphasize the low practical diagnostic value of PEG-based preparation that did not appear to have any positive impact on the DY in our study.

In conclusion, we found no significant difference in overall DYs and quality of bowel preparation. The results of this study reflect 10 years of “real-life” experience with this unique technology, which may often be more generalizable than the data acquired during clinical trials, hence its importance. More prospective data is needed.

What is already known:

Video capsule endoscopy (VCE) is a prime diagnostic modality for small bowel pathologies

Bowel preparation improves VCE visibility

The impact of polyethylene glycol (PEG)-based bowel preparation on the diagnostic yield is still debatable

What the new findings are:

In this large retrospective cohort, PEG-based preparation was not associated with a superior diagnostic yield compared with overnight fasting and clear fluids

Bowel preparation quality was similar between the groups

No clinical benefit of PEG-based preparation in VCE was demonstrated