Abstract
Introduction:
In patients with obscure gastrointestinal bleeding (OBGIB) capsule endoscopy (CE) is the initial diagnostic procedure of choice. Often patients undergo single balloon enteroscopy (SBE) with both diagnostic and therapeutic intention after CE. Although SBE offers a therapeutic benefit, long procedure times, complexity, and invasiveness are drawbacks. We aimed to evaluate the diagnostic correlation between these two modalities after an initial positive CE finding.
Methods:
We performed a retrospective review of 418 patients who underwent CE at our institution from January 2010 to May 2014. A total of 95 patients were analyzed after selecting patients that underwent SBE originally after a positive CE result for the evaluation for OGIB. Agreement beyond chance was evaluated using the κ coefficient. A p value less than 5% was considered statistically significant.
Results:
The mean age of our population was 65.8 ± 12.2 and it was female predominant: 57/95 (60%). The most frequent positive findings were vascular lesions found on SBE in 31.6% and on CE in 41.1%. There was a strong agreement when identifying active bleeding and clots [κ=0.97; 95% confidence interval (CI) 0.92–1.03; p ⩽ 0.0001], and a moderate agreement when diagnosing vascular lesions (0.41; 95% CI 0.21–0.61; p ⩽ 0.0001). There was fair agreement for ulcers (0.26; 95% CI 0.07–0.59; p = 0.005). There was a low correlation between masses, polyps, and others.
Conclusion:
CE still remains the initial test of choice in evaluating stable patients with OBGIB since it has strong-to-fair concordance for the major small bowel findings. However, in cases of severe overt small bowel bleeding, balloon-assisted enteroscopy can be considered the initial procedure of choice since it is therapeutic as well as diagnostic and this approach avoids delays in treatment. Further research should focus on methods to improve interpretation of CE and enhance the ability to evaluate the entire small bowel with SBE.
Introduction
Obscure gastrointestinal bleeding (OBGIB) is a common source of admission and gastroenterology consultation at tertiary care centers. OBGIB is defined as persistent bleeding noted after a negative upper and lower endoscopy and presumed to be located within the small intestine [Zuckerman et al. 2000]. It accounts for approximately 5% of all gastrointestinal bleeding [Tanaka et al. 2008]. Due to the length of the small intestine, and its tortuosity, it is technically very challenging and difficult to perform a complete surveillance even with deep enteroscopy. If the upper and lower endoscopies are nondiagnostic, a capsule endoscopy (CE) is historically completed first to identify the source of bleeding.
CE has been in use since 2001. There are major advantages of using CE, including lower cost, less physician time, and more importantly fewer complications than enteroscopy [Goenka et al. 2014]. In patients with OBGIB, CE has consistently been shown to provide a significantly higher diagnostic yield compared with radiological modalities such as small-bowel angiography, computed tomography scan, and bleeding scan [Gerson, 2012]. The key drawbacks to CE include an inability to provide therapeutic interventions such as hemostasis, potentially missing lesions in between folds of small intestine, being unable to clean blood or debris obscuring lesions, and overinterpretation of normal variants and artifacts as significant lesions [Goenka et al. 2014]. These limitations of CE can be circumvented with deep enteroscopy [single balloon enteroscopy (SBE) or double balloon enteroscopy (DBE)].
SBE allows the location of small bowel lesions, either already identified by CE or new lesions, allows for biopsy collection if necessary, and provides therapeutic interventions including hemostasis [Nakamura et al. 2006]. Other indications for deep enteroscopy include identifying inflammatory mucosal lesions such as in Crohn’s disease, detection of small bowel tumors, and surveillance of polyposis syndrome [Xin et al. 2011]. The major complication identified with deep enteroscopy is the risk of perforation [May et al. 2010]. Limitations of SBE include operator dependency and potential for prolonged procedure time. Availability and cost are similar to those encountered during DBE [Ell et al. 2005]. A study by Marmo and colleagues has evaluated the correlation between DBE and CE, however the concordance between CE and SBE has yet to be studied [Marmo et al. 2009]. The major aim of the study was to evaluate the diagnostic correlation between CE and SBE after an initial positive CE in patients who presented with gastrointestinal bleeding.
Patients and methods
Approval for the study was obtained from the Institutional Review Boards of the University of South Florida and Tampa General Hospital. This was a retrospective study thus consent was not obtained prior to enrolling patients in this study. We performed a retrospective analysis of 418 patients who underwent CE at our institution from January 2010 to May 2014. A total of 95 patients were analyzed after selecting patients who underwent SBE originally after a positive CE result for the evaluation of OBGIB. Demographic data were collected, which included age and sex of the patient. Data were also gathered looking at baseline hemoglobin levels on admission, number of units of packed red blood cells transfused, rebreeding episodes, and number of patients requiring either interventional radiology or surgery for continued or recurrent bleeding during hospitalization.
A standard SBE system (SIF-Q180, Olympus Medical, Center Valley, PA, USA) was used to examine the small intestine. Direction of approach was determined by CE findings. An anterograde route was chosen if location of the lesions was identified in the first 75% of the small bowel on CE. If the lesion was identified in the distal 25% of the small intestine, the retrograde approach was chosen. For some patients with high clinical suspicion, despite negative findings on the initial route of insertion, the opposite route was taken. Patients undergoing the retrograde approach received bowel preparation with 4 liters of polyethylene glycol the day before the procedure. Informed consent was obtained from each patient before the beginning of the procedure. The SBE was performed with a disposable overtube (ST-SB1; Olympus Medical) which is 140 cm long with a 13.2 mm outer diameter. It is equipped with a latex-free balloon at the tip where air can be inflated and deflated from a pressure-controlled pump system allowing for passage through the small bowel. Monitored anesthesia care was used with intravenous propofol and the patient was continuously monitored pre-, intra-, and postoperatively.
The lesions encountered either on CE or SBE were characterized as vascular lesions, active bleeding or clots, ulcerative lesions, masses, or polyps. The location of the lesions was noted as being in the duodenum, jejunum, or ileum.
Statistical analysis
Descriptive statistics were used to generate means and ranges in order to summarize data. The association between dependent and independent variables was assessed using either an independent t test in cases of continuous variables and χ2 test for dichotomous variables. For continuous data, the results were summarized as mean difference (MD) and standard deviation (SD) along with 95% confidence intervals (CIs). For dichotomous data, results were summarized using odds ratio (OR) and 95% CI. Concordance was generated using the κ index with 95% CI and p value was set as statistically significant at less than 5% [Byrt et al. 1993]. All data analyses were performed using SPSS version 22.
Results
A total of 95 patients with OBGIB were evaluated in this study. All patients first underwent CE, which had one or more positive findings, and subsequent SBE. The mean age of our population was 65.8 ± 12.2 years, with a female predominance (60%). Upon admission, the average hemoglobin was 9.40 g/dl and the patients required an average transfusion of 3.2 units of packed red blood cells (PRBCs). Of the 49.5% of patients who required hospitalization, 10 patients (10.5%) required surgical intervention and 2 (2.1%) required arterial embolization with interventional radiology (Table 1).
Clinical features of patients with obscure gastrointestinal bleeding (N = 95).
IR, interventional radiology.
Very few limitations were noted on the patient’s capsule studies. Dark debris, mostly blood products, obscured the views of the small bowel in six patients, while thick mucus secretions were noted in two other studies. The mean gastric emptying time was 29.6 ± 5.01 min, while the mean small bowel transit time was 224.9 ± 12.9 min.
There were two reported complications during SBE. One patient experienced bleeding at the end of the procedure; however the location could not be identified. Perforation of the small bowel was also noted in one procedure. No deaths were noted during the study.
The most frequent positive findings on CE were vascular lesions in 39 patients (41%), followed by active bleeding or clots in 34 patients (36%), and ulcers in 15 patients (16%). Vascular lesions were most frequently found on SBE in 30 patients (31.6%), followed by active bleeding or clots in 25 patients (26.3%), and ulcers in 9 patients (9.5%). Masses and polyps made up a small percentage of findings on CE (2.1%, 6.3%) and SBE (1.1%, 7.4%) (Table 2).
Type of lesions detected with capsule endoscopy and single balloon enteroscopy (SBE).
There was a strong degree of concordance between findings on CE and SBE when identifying active bleeding or clots, with a calculated κ index of 0.97 (95% CI 0.92−1.03). Moderate agreement was found while looking at vascular lesions, with a calculated κ index of 0.41 (95% CI 0.21−0.61). There was a fair agreement for ulcers, with a κ value of 0.26 (95% CI 0.07−0.59). The degree of concordance was not significant for the diagnosis of masses and polyps (Table 3).
Type of lesions detected with capsule endoscopy and single balloon enteroscopy (SBE) for obscure gastrointestinal bleeding.
CI, confidence interval.
The majority of positive findings were identified in the jejunum on CE (n = 63) and SBE (n = 36), followed by the duodenum on CE (n = 48) and SBE (n = 20). The ileum had the least number of positive findings for both procedures, with 41 positive findings on CE and 6 on SBE (Table 4).
Location of lesions detected with capsule endoscopy and single balloon enteroscopy (SBE).
Discussion
Several studies have demonstrated comparable performance and diagnostic yields for evaluation of the small bowel using either SBE or DBE. SBE has recently been identified as a simplified and less complex procedure [Domagk et al. 2011]. This study sought to explore the concordance between findings on CE and SBE. With the advent of CE and balloon-assisted enteroscopy, the ability to visualize the entire small bowel has significantly increased the likelihood of identifying the cause of OGIB [Westerhof et al. 2009].
Classically, CE is completed first due to lower costs and decreased risks. Once the location of the lesion is identified on CE, the direction of approach using balloon-assisted enteroscopy (anterograde versus retrograde) is determined in order to perform therapeutic interventions [Gay et al. 2006]. While advantageous in determining location of lesions, CE lacks the ability to utilize air insufflation or washing to better visualize potential lesions, mark lesions for surgery, initiate therapy, or obtain histological samples [Westerhof et al. 2009]. This can result in a significant delay of therapeutic intervention, as capsule studies can take up to 8 h to complete and require a skilled clinician to analyze close to 50,000 images [Zhao et al. 2015].
In order to justify the potential delay of therapy and the additional expense of CE, it is important that CE findings demonstrate concordance with the findings of subsequent deep enteroscopy. In our study, we found that CE and SBE have a strong agreement for active bleeding and clots. A moderate degree of concordance existed while identifying vascular lesions, with a fair agreement for ulcers. There is a significant discrepancy between these two modalities, especially when it comes to vascular lesions and ulcers. These discrepancies may be due to the failure to reach lesions on SBE or overinterpretation of findings on CE. Rates of complete enteroscopy during SBE are highly variable, with current studies estimating the rate at 12.4 ± 9.8% [Lenz and Domagk, 2012]. Overinterpretation resulting in false positives on CE are common; for example, bulges due to peristalsis or pressure from adjacent organs may be misinterpreted as submucosal lesions, and small red spots may be misidentified as angioectasias. Overinterpretation of CE findings may have played a significant role in the moderate-to-fair concordance found with vascular lesions and ulcers in our study. Another possible cause of lack of concordance with ulcers is the resolution of nonsteroidal anti-inflammatory drug induced ulcers prior to performance of deep enteroscopy since these agents are usually stopped once bleeding is recognized. CE is performed first in these patients with a delay of several days or more before deep enteroscopy is done. Poor concordance with tumors and polyps may again reflect overinterpretation on CE or inability to reach findings on SBE; however, with so few polyps and masses in our study this analysis is likely not valid. We believe poor concordance with polyps and tumors was secondary to missed lesions on CE being found on deep enteroscopy. This is more than likely due to the fact that 100% of the small bowel surface area is never seen on CE.
Both procedures were well tolerated among patients in our study. Capsule retention for longer than 2 weeks occurred in one patient. This capsule eventually passed after through-the-scope balloon dilation of a suspected stricture in the terminal ileum during SBE. The patient experienced no symptoms such as pain, nausea, or vomiting, and did not experience an obstruction. Two patients developed complications following SBE: one experienced bleeding and the other a small bowel perforation. Even though it is more invasive than CE, multiple studies have established the safety of SBE [Aktas et al. 2010; Manno et al. 2010]. Given the discrepancies in agreement between CE and SBE, certain patients without severe comorbidities from cardiopulmonary, renal, or hepatic disease may benefit from undergoing a SBE initially, without first having a CE.
A limitation of this study is that it was performed as an observational retrospective study. In addition, a large number of patients presenting at our tertiary care institution were referred for SBE only after a positive CE that was conducted and interpreted elsewhere. These patients were excluded from the study.
In conclusion, in patients with OBGIB we found a strong degree of concordance between CE and SBE for active bleeding and clots, but only moderate concordance for vascular lesions and fair concordance for ulcers. These discrepancies can largely be attributed to overinterpretation on CE and, to a lesser extent, inability to reach findings on SBE. CE still remains the initial test of choice in evaluating stable patients with OBGIB since it has strong to fair concordance for the major small bowel findings and is helpful in planning the route of balloon-assisted enteroscopy (antegrade versus retrograde). In patients with severe overt small bowel bleeding, balloon-assisted enteroscopy can be considered as the initial procedure since it is therapeutic as well as diagnostic, and this approach avoids delays in treatment. If CE is normal or negative, balloon-assisted enteroscopy should still be considered since lesions including tumors and polyps can be missed on CE. Further research should focus on methods to improve interpretation of CE and enhance the ability to evaluate the entire small bowel with SBE.
Footnotes
Acknowledgements
All authors contributed equally.
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflict of interest statement
The authors declare that there is no conflict of interest.