Owing to the characteristics of the small bowel anatomy, a sensitive and specific tool for the diagnosis of small bowel disease has been lacking. In our study, we found that DBE was useful to diagnose or confirm small bowel CD in patients after exclusion of abnormal changes in the upper gastrointestinal tract and colon. The absence of a gold standard for diagnosis also makes confirming small bowel CD difficult. For diagnosis of small bowel CD, many new techniques can be used to identify small bowel lesions[6, 10]. Recent studies have shown that the imaging techniques MRE and CTE have high sensitivity and specificity for recognizing active inflammation in the small bowel, especially for identifying stenosis, penetration, and extra-intestinal manifestations. On CTE, enteric findings such as mural hyper-enhancement, bowel wall thickening, mural stratification, engorged vasa recta (“comb sign”), and increased attenuation of the mesenteric fat are features of active inflammatory small bowel CD. According to the literature, the most common manifestation of CTE in established CD patients is thickening of the intestinal wall, up to at least 80%, in agreement with our results. Although this feature is not characteristic, the abnormalities in CTE should be different from those in cryptogenic multifocal ulcerous stenosing enteritis, intestinal involvement of diffuse connective tissue disease, and chronic ischemic bowel disease. CTE can indicate the location and extent of the lesion, providing clues to direct the insertion direction of DBE. Their noninvasiveness makes CTE and MRE acceptable and feasible in clinical practice[7, 12].
VCE is a noninvasive method with high sensitivity for detecting small bowel lesions. It can enable visualization of mucosal lesions, particularly superficial lesions[13, 14]. Lesions detected by VCE are nonspecific, and CD cannot be distinguished from lesions caused by nonsteroidal anti-inflammatory drugs (NSAIDs) or other etiologies, on the basis of endoscopic images. The randomness of the image capture in VCE results in high negative predictive value and lower specificity. Positive consequences must be further identified and confirmed. Failure to obtain tissue for pathological results and the potential risk of capsule retention are major disadvantages of VCE. DBE is superior to radiology for detecting superficial lesions such as aphthous ulcers and erosions. Compared with VCE, it can accurately describe the location and morphology of lesions and surrounding mucosa (such as the appearance of pebbles and edema), thus helping to distinguish CD from other diseases[17, 18].
DBE is a helpful method when no abnormalities are observed using radiology and VCE but small bowel CD is suspected. Since the development of DBE in 2001 by Yamamoto et al., its diagnostic ability in small bowel diseases has been extensively studied. It allows for direct visualization of the small bowel mucosa and has a broader and clearer field of vision than VCE. CD is characterized by chronic granulomatous intestinal inflammation, and the lesions tend to be segmental and discontinuous. Multifocal lesions may have areas of different activity, and acute inflammatory and fibrotic strictures may be present at the same time. DBE can be used to visualize large portions of the small bowel, alone or in combination, and to examine small bowel inflammatory lesions. The earliest and most characteristic endoscopic finding in small bowel CD is aphthous ulcers, which enlarge and deepen as the disease progresses, thus forming longitudinal ulcers. CD inflammation is often discontinuous, bordering on normal tissue, thereby resulting in segmental lesions. A cobblestone-like appearance occurs when longitudinal ulcers pass through areas of normal or inflamed tissue. Other common endoscopic findings are thickening of the intestinal wall, varying degrees of stenosis, and cluster-like polyposis. The morphological features detected by DBE play a crucial role in the diagnosis of CD. A longitudinal ulcer along the mesenteric side is a typical morphological feature that can help to distinguish CD from other diseases that cause intestinal inflammation. Ulcers associated with ischemia, intestinal tuberculosis, and Behcet’s disease are common on the anti-mesenteric side of the bowel, whereas NSAID-associated ulcers have no such tendency in the intestinal lumen. The combination of typical macroscopic features with clinical manifestation, laboratory tests, smoking status, and family history may be sufficient to diagnose CD.
Ideally, DBE can provide pathological support for the diagnosis of small bowel CD[22, 23]. The histology usually detected in patients with established CD includes focal (discontinuous) chronic inflammation, focal crypt irregularities, and granulomas. Non-caseous granulomas are generally recognized as the most important microscopic features detectable for the diagnosis of CD. Non-caseous granuloma and at least one other microscopic feature (focal chronic inflammation or focal crypt irregularity) can be considered for CD. In a retrospective study, despite positive macroscopic findings from DBE, 58% of the patients had normal or nonspecific histology, and 45% of patients were treated as having CD on the basis of a combination of histology, endoscopic appearance, clinical symptoms and laboratory tests. Although the discontinuity of inflammation and the superficiality of the biopsy tissue results in a lower chance of obtaining a granuloma under endoscopy, 10–30% of histological findings can still provide evidence to establish a diagnosis. Clinical diagnosis requires pathological support to confirm the diagnosis of small bowel CD and to help differentiate it from intestinal tuberculosis, Behcet’s disease, lymphoma, and other diseases. Small bowel CD can be diagnosed using the six diagnostic points proposed by the WHO. The diagnosis of small bowel CD involves clinical, endoscopic, radiological, and histological features; however, satisfying all the criteria may be impossible or unnecessary in practice. DBE should be considered complementary to other diagnosis methods. In ambiguous cases, the “test of time” is useful for CD diagnosis. Recurrent complaints, responses to therapy, and recurrent symptoms after stopping therapy may eventually verify the diagnosis.
When DBE presents as only superficial ulcers and mucosal inflammation in the small bowel, patients cannot be sufficiently diagnosed with CD. Studies have reported that using endoscopic ultrasound (EUS) with DBE is more helpful in diagnosing inflammatory bowel disease because it shows the hierarchical structure of the intestinal wall of the small bowel[26, 27]. Very few studies have reported the application of EUS with DBE in the small bowel, but EUS has been widely used in the diagnosis of digestive tract disease[28-31]. In addition to aiding in the diagnosis of small bowel CD, DBE can be useful in the provision of therapeutic interventions. Retrieval of retained VCE devices has been reported in several studies[8, 32]. Owing to the recurrent nature of the disease, patients are prone to intestinal stenosis, and many patients will require multiple surgeries during the disease course. Surgical removal of the stenosis is a recognized solution, and half of patients require surgery within the first decade of diagnosis. A meta-analysis has reported that small bowel clinical recurrence occurs in approximately 28% of patients after total colectomy with permanent ileostomy for colonic CD. Endoscopic balloon dilation (EBD) is a safe and effective method that can replace small bowel resection in some cases.
In our study, no adverse events occurred (e.g., bleeding, perforation, pancreatitis and sedative-related adverse events) after DBE. According to different reports, the incidence of DBE complications is between 1.2% and 1.6%[35, 36]. When the small bowel is contorted, or stenosis is present, any further insertion of the endoscope would increase the risk of perforation. For this reason, we stopped insertion in such situations. Determination of the most appropriate DBE insertion route is based on lesion location information provided by CT or other additional examinations. For the seven patients who underwent VCE, their insertion route was based mainly on the results of VCE. When the VCE and CT results were very different or without clear evidence of small bowel involvement, we chose the oral route for insertion because deeper insertion can be achieved via the oral route, increasing the potential of finding the lesions. According to Mays’ method, which is widely used in clinical practice and has been found to be effective in estimating the depth of endoscopic insertion, we estimated insertion depth by calculating the number of strokes (insertion and withdrawal cycles).
There are several limitations in this study that must be discussed. First, the study was a retrospective study with a small sample of patients. Because of the low incidence and low prevalence of small bowel CD in Asian regions, in this single center study, we were unable to obtain a larger sample, which may have affected diagnostic accuracy. Second, because skilled endoscopists and anesthesiologists are required, the application of DBE in the diagnosis of small bowel CD is currently not widely used. Because our hospital is a tertiary referral center, our patients may not be representative of patients with small bowel CD. Many of the patients in this study had a relatively long medical history, and their condition was quite serious; thus, these patients may have had typical and obvious macroscopic features, enabling easier detection of lesions via DBE. On the one hand, this may have increased the diagnostic accuracy of DBE; on the other hand, opportunities to identify lesions may have been missed because of complicated abdominal conditions that limited the use of DBE, such as surgical adhesion and deep ulcers or stenosis of the bowel.
In conclusion, in patients with suspected small bowel CD, we recommend the use of DBE for the comprehensive evaluation of the gastrointestinal tract, thus contributing to clinical diagnosis in cases of negative EGD and colonoscopy. DBE is suitable when VCE or radiological examination reveals abnormal lesions, or when the results of these two methods are negative but small bowel CD is highly suspected. In the future, more indications using DBE will be developed to diagnose, monitor and treat small bowel CD.