Small-bowel tumors (SBTs) are a rare entity comprising 0.6% of all new cancer cases in the US [1] and only 3% of all gastrointestinal (GI) tumors, despite the fact that they involve the longest part of the GI tract [2]. In recent years their incidence is on the rise, probably due to the wider availability of high performance diagnostic modalities for SB investigation and the increasing incidence of specific SBTs, namely SB neuroendocrine tumors (NETs) [3].

SBTs represent a heterogenous group of approximately forty different histological subtypes with different distribution throughout studies [4] and the most common being adenocarcinoma (30–45%), NENs (20–40%), lymphomas (10–20%) and sarcomas (10–15%) [5]. There is significant geographic diversity of the histological distribution of SBTs and specifically in the US the most common SBTs are NETs (35–42%) followed by adenocarcinoma (30–40%) [6]. In China adenocarcinoma (33.33%) is the most prevalent subtype, closely followed by leiomyosarcoma (32.91%) [7], whereas in Thailand, Gastrointestinal Stromal Tumors (GISTs) comprise the vast majority of SBTs (39.5%) [8].

The rarity of SBTs, as well as the absence of specific clinical manifestations render their diagnosis challenging, requiring not only a high degree of clinical suspicion but also the implementation of various investigations, including dedicated cross-sectional imaging and endoscopy.

The most common clinical scenario leading to the diagnosis of a SBT is that of suspected SB bleeding (SSBB) and otherwise unexplained iron-deficiency anemia (IDA), accounting for 3.5–5% of cases with this indication [9]. Other non-specific symptoms include abdominal pain, anorexia, weight loss and obstructive symptoms in case of advanced disease.

Nevertheless, there are certain groups of patients at higher risk of harboring a SBT, including those with non-responsive/complicated celiac disease, hepatic metastasis in the setting of a NET of unknown primary and advanced (stage III/IV) melanoma patients especially with positive Fecal Occult Blood Test (FOBT) [9]. Moreover, patients diagnosed with inherited polyposis syndromes represent a distinct subset of patients requiring regular SB surveillance due to their genetic predisposition for SBTs [9]. Familial adenomatous polyposis, (FAP) and Juvenile polyposis syndrome (JPS) require inspection of the duodenum with forward viewing endoscopy. In FAP additional inspection of the papilla with cap-assisted or side-viewing endoscopy is important and in patients with a high polyp burden, SBCE can be considered. Finally, investigation of the entire SB is necessary by MRE or SBCE in Peutz-Jeghers syndrome (PJS), followed by Device-Assisted Enteroscopy (DAE) for removal of large (≥15 mm) or symptomatic polyps.