When compared with tumours affecting other gastrointestinal segments, small bowel tumours (SBTs) are rare. Moreover, the term SBT is almost an umbrella term, including very different neoplasms, both benign and malignant, with different histological subtypes and biological behaviours. Overall, more than 40 different histological subtypes of SBTs have been identified. Although the prevalence of different histological subtypes varies across studies, approximately 30–45% of SBTs are adenocarcinomas, 20–40% neuroendocrinetumours (NETs), 10–20% lymphomas and 10–15% sarcomas [1–5,6▪▪].
Because of their heterogeneity and rarity, there are scarce reports on the incidence and prognosis of SBTs. Moreover, the majority of these articles come from tertiary referral centres and is focused on a subtype of SBT and/or on a subgroup of patients at an increased risk to develop SBT (e.g. patients with FAP, Peutz–Jeghers syndrome, Lynch syndrome, Cowden syndrome, Crohn's disease, refractory celiac disease and so on). However, large population-based studies including all SBT cases diagnosed in a well defined population have recently become available [6▪▪,7,8,9]. The estimated yearly incidence of SBTs, based on the US Surveillance Epidemiology and End Results Program (SEER) [10▪▪], the Cancer Research UK Organisation  and the recently published National Danish registry , ranges between 1.1 and 2.3 new cases per 100 000 inhabitants. Although the incidence of different histological subtypes varies widely across studies, all of them generally show a steady increase in the incidence of SBTs over time [1,3,5,7–9,10▪▪,11] (Fig. 1).
Since the early 1990s, the overall SBT incidence rates has more than doubled (121% increase) in the UK  and it has been calculated that the rate for new SBT cases has been rising on average 1.9–2.4% each year over the last 10 years [9,10▪▪,11]. Although there are no obvious explanations for this phenomenon, the introduction in the last 15 years of new diagnostic tools, dedicated to the study of the small bowel, has been called into question.
The 5-year survival rate of SBTs varies widely across population-based studies: it has been reported to be 33% in the Danish National registry , 48% in the EUROCARE project  and 67% in the SEER program [10▪▪]. This wide variation mainly depends on the prevalence of different histological subtypes across studies. Moreover, stratifying the results according to the different histological subtypes, similar figures were observed. The 5-year survival rate is higher in patients with NETs (50–80%) and lower in patients with small bowel adenocarcinomas (20–30%) [5,9,13]. Nevertheless, regardless of the histological subtype, SBT stage at diagnosis has a strong influence on the length of survival and determines treatment options. According to SEER data, the 5-year survival for localized SBT is 85.3%, whereas it decreases to 40% when distant lymph nodes or other organs are involved [7,8,9,10▪▪,14–17].
All these observations underline the importance of an early diagnosis, which is often delayed in everyday clinical practice. Fortunately, recent data suggest that the introduction of diagnostic techniques specifically dedicated to the evaluation of the small bowel might change these figures [18–20].
DIAGNOSTIC TECHNIQUES FOR THE STUDY OF THE SMALL BOWEL: PROS AND CONS
Although SBTs could be suspected by means of several routine diagnostic tests [e.g. abdominal ultrasound, abdominal computer tomography (CT) and so on], at the present time, imaging tools specifically designed for the study of the small bowel include capsule endoscopy, device-assisted enteroscopy (DAE) and small bowel cross-sectional imaging techniques such as CT or magnetic resonance (MR) enterography or enteroscopy.
Since its introduction in clinical practice, capsule endoscopy has demonstrated a high diagnostic yield (up to 50%)  by identifying small bowel mucosal lesions, including SBTs in 3–10% of patients receiving capsule endoscopy [22,24,25▪▪]. CE represents a noninvasive invasive diagnostic tool, well received by patients, easy to perform and able to accurately evaluate the whole small bowel mucosal surface in a single procedure in most cases. However, in the setting of patients with SBTs, this technique has shown some important limitations. In addition, the presence of mass-forming lesions frequently reduces the small bowel lumen size, favouring capsule retention. In fact, the retention rate in patients with SBTs is up to 10 times higher (up to 21%) than that observed in patients with suspected small bowel bleeding (about 1–2%) [21–24,25▪▪,26]. However, capsule retention is generally asymptomatic, and as most patients with SBT require a surgical intervention for resection, retrieval of the retained capsule can happen at that time. On the contrary, the main limitation to the use of the capsule as a diagnostic tool in this setting of SBT patients is the risk of missing SBTs, particularly in the proximal SB. The SBT miss rate was estimated approximately 20% in a large retrospective study  and it has unfortunately been confirmed even in more recent studies in which either DAE or surgery has been used as a reference standard [20,28]. Furthermore, it is important to highlight that a significant proportion of SBTs originates from the submucosal layers and may not lead to significant changes in the mucosal surface. Although specific scores have been developed for the distinction between innocent mucosal bulging and submucosal lesions [29,30], the identification of submucosal lesions of the small bowel remains one of the most challenging tasks for capsule endoscopy reviewers. Moreover, capsule endoscopy is a purely diagnostic tool that does not allow biopsy sampling or other forms of sensing. In order to overcome these limitations, DAE has been developed. DAE encompasses the use of traditional endoscopes, modified in length and calibre, and of specifically designed overtubes (equipped with tools that allow anchoring the scope to the small bowel wall). This system allows an accurate evaluation of long small bowel segments. The main advantage of DAE is to allow both a detailed evaluation of the small bowel surface with tissue sampling, and endoscopic treatments (i.e. haemostasis, polypectomy, retrieval of retained capsules and so on) or of placing tattoos for more precise identification of SBTs at the time of surgery. In a recent multicentre Korean study , the authors reported that therapeutic plans were changed, following DAE, in more than 60% of patients with SBTs. Recently, Murino et al.[32▪] showed that, as far as submucosal tumours are concerned, endoscopic ultrasonography (EUS) performed during DAE is a well tolerated and useful technique, which allows better submucosal tumours characterization, driving further patient management.
Unfortunately, DAE is an invasive and time-consuming technique, which often requires deep sedation and, even in expert hands, rarely allows the evaluation of the entire small bowel in a single examination. Furthermore, DAE requires a well trained, cooperative and dedicated team and is characterized by relevant complications (i.e. perforation, bleeding and sedation-related complications). Finally, at least in western countries, this technique is not particularly widespread and is often available only in highly specialized tertiary referral centres.
Conversely, the cross-sectional radiological techniques are quickly available worldwide. However, for many years, these techniques yielded disappointing results in the study of the small bowel and the small bowel follow-through represented for a long time the radiological reference standard. Nevertheless, in recent years, the continuous technological improvement in the field of cross-sectional radiology and the introduction of luminal contrast agents (such as neutral or near-water contrast agent for CT and biphasic contrast agents for MRI) have significantly increased the ability of radiological cross-sectional techniques in evaluating the small bowel. These contrast agents allow distention of the lumen of the small bowel, favour the identification of intraluminally growing lesions and increase the contrast between the intestinal wall and the luminal content. Thanks to the use of these contrast agents, radiologic cross-sectional techniques currently have a high sensitivity in identifying tumour lesions of the small bowel (up to 85–94%) [32▪,33▪,34,35] and allow, in a single examination, both identification and staging of SBTs. Staging a neoplastic disease represents a crucial step for planning further diagnostic and/or therapeutic procedures.
However, one of the main limitations of these methods is the low specificity for findings; inflammatory changes, the small bowel wall movement, artefacts and postsurgical adhesions may mimic SBTs . Last but not least, the volume of the contrast medium to be ingested, to reach an adequate small bowel luminal distention, is high (1–3 l); therefore, the patient's compliance to small bowel enterography is often suboptimal [37,38]. The use of nasogastric tubes for the infusion of the contrast medium directly at the duodenal level has been proposed, but this policy is poorly tolerated, as well. In order to increase patient acceptance, a virtual enteroscopy technique has been proposed: the small bowel is distended using warm carbon dioxide (CO2) that is inflated automatically through a dedicated nasojejunal tube equipped with an antireflux balloon. In a recently published prospective article including 17 patients with suspected SBTs, this new technique showed an excellent patient tolerance combined with high diagnostic accuracy (sensitivity and positive predictive value were 92.0 and 92.0%, respectively) [39▪▪].
At the present time, large, prospective studies comparing different techniques for the study of the small bowel in the setting of SBT are lacking [40–43]. There are only few small retrospective studies, which are affected by relevant methodological bias and yield conflicting results. Moreover, considering the available literature in a comprehensive manner and taking into account the pros and cons of the different techniques for the study of the small bowel, it is clear that they are complementary, rather than alternative. Moreover, a reasoned and balanced combination of the different tests allows to reach a final diagnosis and to plan further management, overcoming the limitations of each single procedure.
DIAGNOSIS AND MANAGEMENT OF SMALL BOWEL TUMORS
SBTs usually remain asymptomatic for years and the clinical presentation is often indolent and nonspecific. Therefore, most cases of SBTs are unexpectedly diagnosed in the course of a diagnostic workup of patients with suspected small bowel bleeding, unexplained iron-deficiency anaemia and persistent abdominal pain, or during the follow-up of other clinical conditions (e.g. inflammatory bowel disease, coeliac disease and so on).
In the setting of SBTs, DAE should be the preferred diagnostic modality, taking into account its ability to both detect and sample lesions. Nevertheless, in the everyday clinical practice, given the high rate of SBT patients presenting with suspected small bowel bleeding, its noninvasive nature and the ability of inspecting the entire organ, capsule endoscopy has become increasingly used and it is often the first test showing findings compatible with SBTs. Nevertheless, as previously highlighted, capsule endoscopy lacks in specificity; therefore, when a suspected SBT is identified, in the large majority of cases, further tests are needed. In this setting, DAE represents the ideal confirmatory test. In fact, when guided by capsule endoscopy findings, the diagnostic accuracy of DAE increases dramatically. Furthermore, the timing of capsule endoscopy findings is an excellent indicator to decide which DAE approach (per-oral or per-anal) has to be planned. Cross-sectional imaging tests are often used as initial diagnostic approach, especially when capsule endoscopy is unavailable and/or contraindicated, or as confirmatory tests in case of positive capsule endoscopy (Fig. 2). When radiological examinations are performed as initial tests, because of the limited specificity, their findings should be verified by DAE. Furthermore, radiological tests have the fundamental role of staging by evaluating the involvement of extra-intestinal organs, local invasion and lymphatic diffusion. For this reason, even when the diagnosis has already been reached by performing endoscopic procedures, all patients with SBTs invariably receive cross-sectional imaging evaluation. When the initial method of investigation, whether radiological or endoscopic, is negative, taking into account the limitations of the individual diagnostic procedures, the diagnostic-therapeutic work-up must not be stopped. Several studies have recently reported cases of SBTs missed by capsule endoscopy and identified by means of DAE and/or dedicated small bowel cross-sectional imaging techniques [28,44,45] (Fig. 3).
Despite recent technical improvements, in SBT patients, the result of a single diagnostic test is often insufficient to reach a definite diagnosis. The diagnosis of SBT represents a true and unique puzzle, whose composition often requires the combination of different diagnostic examinations. This once again reinforces the concept that, in this subgroup of patients, the currently available diagnostic methods (namely DAE, capsule endoscopy and cross-sectional imaging techniques dedicated to the study of the small bowel) are complementary rather than alternative.
Financial support and sponsorship
The authors did not receive any founding or support for the present article.
Conflicts of interest
There are no conflicts of interest.
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Keywords:Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
capsule endoscopy; device-assisted enteroscopy; small bowel cross-sectional imaging techniques; small bowel tumours