{"paper_id":"3b1d6bf9-7816-438a-8ac6-1acefe40ee86","body_text":"The prevalence of small-bowel adenocarcinoma (SBA) is very low, present in just 5% of\nall cases of gastrointestinal malignancy. 1  This is due to the alkaline, low-bacterial,\nhigh-immunoglobulin A (IgA) and high-hydroxylase environment in the GI\ntract. 2  Moreover,\n de novo  SBA in the terminal ileum is the least common of the\nSBA types, found in only 10% of all SBA cases. 3  Nonetheless, the terminal ileum is the most common site of\nSBA in patients with Crohn’s disease (CD), with 75% of SBA cases presenting\nin patients with CD according to a retrospective study conducted from 1993 to\n2009 4  ; notably, this makes\nthe diagnosis of terminal ileal adenocarcinoma in the absence of CD more difficult\ndue to the high possibility of misdiagnosing it as CD. CD is a well-known risk\nfactor for SBA. A 2006 meta-analysis reported a relative risk of 31.2 (95%\nconfidence interval: 15.9–60.9) for small-bowel neoplasm in CD. 5  In contrast, we herein introduce two\ncases of  de novo  SBA in the terminal ileum mimicking CD on\nconventional CT, CT enteroclysis and MRI enteroclysis in the absence of a final\ndiagnosis of CD.\n\nA 64-year-old female presented with a 2-month history of central intermittent\nnon-radiating abdominal pain with vomiting. There was no haematemesis or\nhaematochezia. There was no significant recent weight loss. She had a background\nhistory of polymyalgia rheumatica (on long-term steroid), chronic obstructive\npulmonary disorder and use of a cardiac pacemaker. She had a smoking history of 45\npack a year but a low degree of alcohol consumption. There was a notable family\nhistory of both bowel and breast cancer.\nOn clinical examination, left iliac fossa tenderness with guarding was noted. Test\nresults of blood drawn at admission showed elevated C-reactive protein (CRP)\n(80 mg l −1 ) and elevated faecal calprotectin\n(402 μg/g).\nInitially, gastroscopy and colonoscopy were performed, revealing the existence of\nnormally appearing mucosa. Meanwhile, CT chest–abdomen–pelvis (CAP)\nimaging showed mild thickening of the distal and terminal ileum throughout a section\nmeasuring approximately 10 cm long but no signs of colonic mass or malignancy\n( Figure 1 ). As MRI was contraindicated due\nto the patient’s implanted cardiac pacemaker, CT enteroclysis was performed\nwith volume acquisition following intravenous contrast approximately 12 weeks after\nthe initial CT CAP. This assessment also showed thickening of the mucosa of the\nterminal ileum, extending to the ileocaecal valve, yet normal appearances of the\nremainder of the small and large bowels. Clinical and radiological findings\nsuggested possible terminal ileitis with CD.\nContrast enhanced CT scan of the abdomen and pelvis in coronal plain\ndemonstrating an approximately 10 cm segment of terminal ileum which\nshows mural thickening and mild mural hyperenhancement. No locoregional\nlymphadenopathy or proximal small bowel dilatation.\nBased on the image findings and clinical pictures, the patient received 40 mg\nof methylprednisolone intravenously bd for 2 days and, as her symptoms improved, she\nwas transferred to 40 mg of oral prednisolone 40 mg once daily as a\ntapering dose. She was discharged with a follow-up plan to be seen by a\ngastroenterologist in 8–10 weeks’ time as an outpatient.\n3 months later, the patient re-presented with worsening symptoms as her steroid dose\nwas reduced. There was mucus apparent in the stool but no haematochezia. Her white\nblood cell count (15.45 × 10 9 /L) and CRP level\n(75 mg l −1 ) were elevated. On clinical\nexamination, her abdomen was soft but mildly tender. An urgent colonoscopy was\nperformed which revealed a terminal ileum tumour. A cold biopsy was taken, which\nconfirmed a moderately differentiated adenocarcinoma. Contrast enhanced CT CAP was\nperformed for staging which showed more prominent mural thickening and mild\nhyperenhancement of the terminal ileum. However, there was no locoregional\nlymphadenopathy or proximal small bowel dilatation ( Figure 2 ).\nContrast enhanced CT scan of the abdomen and pelvis in coronal plain\ndemonstrating the previously known segment of terminal ileum which now\nshowing more prominent mural thickening and mild hyper enhancement. No\nlocoregional lymphadenopathy or proximal small bowel dilatation.\nAt this point, elective laparoscopic right hemicolectomy was pursued.\nPost-operatively, the histopathology sample of the right hemicolectomy confirmed\nulcerated, moderately differentiated adenocarcinoma in the terminal ileum, which had\na focal mucinous component ( Figure 3 ). Notably,\nthe latter formed approximately 25% of the tumour, without caecal involvement.\nHistopathology sample from the terminal ileum showing moderately\ndifferentiated adenocarcinoma in the terminal ileum. Tumour infiltrates\n4 mm the beyond the muscularis propria.\n\nA 60-year-old female presented with a 3-day history of severe generalised abdominal\npain but without haematochezia, diarrhoea or significant recent weight loss. She did\nnot have any family history of cancer or inflammatory bowel disease but did have a\nbackground history of abdominoplasty for cosmetic reasons as well as hysterectomy\nand oophorectomy for endometriosis. She was an ex-smoker who quit 12 years prior to\nthe current presentation.\nUpon clinical examination, the abdomen was tender in the right and left iliac fossa\nbut per rectum examination findings were unremarkable. Blood biochemistry results at\nthe time of admission involved a mildly increased CRP level of\n25 mg l −1  but, the rest of the laboratory\nfindings were unremarkable.\nFurther investigation with CT CAP imaging revealed an oedematous tubular structure\nadjacent to the caecum with associated surrounding inflammatory changes, marginally\nenlarged lymph nodes and free pelvic fluid ( Figure\n4 ). It prompted a provisional diagnosis of small-bowel inflammation. The\npatient continued to improve with intravenous piperacillin/tazobactam. Then she was\nreviewed by the gastroenterology team and the possibility of CD was considered. The\npatient was discharged with oral co-amoxiclav and 9 mg of budesonide once\ndaily as a tapering dose along with a follow-up outpatient colonoscopy in 6 weeks. 5\ndays later, the patient re-admitted with worsening cramping abdominal pain together\nwith nausea and vomiting. An abdominal X-ray showed mildly dilated loops of small\nbowel. MRI enteroclysis was subsequently performed, revealing a 3.5 cm\nsegment of terminal ileum displaying mural thickening, luminal narrowing and mucosal\nhyperenhancement, suggesting inflammatory stricture of the terminal ileum. The\npatient was treated with a course of intravenous methylprednisolone and oral\nmetronidazole and her symptoms again improved.\nContrast enhanced CT scan of the abdomen and pelvis in axial plain\ndemonstrating an approximately 8 cm segment of terminal ileum which\nshows mural thickening and hyperenhancement. No locoregional lymphadenopathy\nor proximal small bowel dilatation. Small volume free fluid present.\nWhile awaiting her outpatient colonoscopy visit, she presented again after 1 month,\nwith central, intermittently colicky abdominal pain with vomiting. However, there\nwas no haematochezia. On examination, the patient’s abdomen was distended and\nmildly tender. Blood biochemistry showed a mildly increased CRP level\n(39 mg l −1 ) but otherwise normal full blood\ncounts and urea and electrolytes. CT CAP imaging was repeated, showing a segment of\npossible CD within the terminal ileum and ascending colon, with dilatation of the\nileum proximal to the inflammatory stricture. Probable further skip lesions were\nseen within the jejunum but no intra-abdominal abscess was apparent ( Figure 5 ). An urgent diagnostic laparoscopy was\nperformed. Intraoperatively, extensive peritoneal and small-bowel mesenteric\ndeposits were found. Therefore, a defunctioning loop ileostomy was formed and\nperitoneal biopsies taken. Biopsy results confirmed poorly differentiated\nadenocarcinoma of the terminal ileum with multiple peritoneal metastases ( Figure 6 ).\nContrast enhanced CT scan of the abdomen and pelvis in axial plain\ndemonstrating persistent mural thickening of the terminal ileum which shows\nmural thickening and hyperenhancement. No proximal small bowel dilatation.\nSmall volume free fluid seen on previous study mostly resolved. However,\nthere are few borderline ileocolic lymph nodes and subtle peritoneal nodules\n(not demonstrated on this image).\nHistopathology sample of peritoneal biopsies showing poorly differentiated\nadenocarcinoma. There is infiltration of the subserosal fibrous tissue by a\npopulation of atypical epithelial cells arranged as single cells and\nglandular structures with evidence of mucin production.\n\nCD is a more common diagnosis than SBA in light of terminal ileal changes on imaging\nwith abdominal pain. The current gold-standard for diagnosing CD is ileocolonoscopy\nand the conduct of biopsies to examine each colonic segment. CT and MRI are\nfundamental tools for monitoring small intestinal involvement and penetrating\nlesions. Nevertheless, the diagnosis of CD should ultimately be comprehensive,\ntaking into account all clinical examinations, radiological findings, blood results\nand ileocolonoscopy with histology in addition to the patient’s treatment\nresponse.\nIn CD, the common findings on CT and MRI enteroclysis include mural hyperenhancement,\nwall thickening, ulcers, stenosis and a phenomenon of vasa recta engorgement known\nas the ‘comb sign’. 6 \nAmong these, mural hyperenhancement and bowel-wall thickening are the most common\nfindings. The main advantage of MRI is the lack of patient exposure to radiation;\nmoreover, it is superior at detecting fistulas, distinguishing between inflammatory\nor fibrous changes and strictures. It can also collect information about small bowel\nmotility. Changes in CT and MRI enteroclysis in patients with SBA can look very\nsimilar to those with CD. The most common appearance of SBA is luminal narrowing,\ncaused by annular or semi-annular mural thickening. There could be heterogeneous\nenhancement of the involved small bowel segment. Atypically, there can be polypoid\nlesions with well-defined margins or ulcerations. 7  In the early stages of CD or SBA, thickening and\nhyperenhancement of the mucosa with bowel-wall stenosis may be almost\nindistinguishable, which could pose a great challenge for diagnosis on\ncross-sectional imaging.\nTo understand the prevalence of the presentation of SBA as CD, a literature search\nwas conducted in the PubMed database. Both broad and specific terms such as\n‘adenocarcinoma’, ‘carcinoma/cancer’ or\n‘tumour/tumor’; ‘small bowel’ or\n‘ileum/ileal’; and ‘Crohn’s’ as well as\n‘without’, ‘mimicking’, ‘simulating’ or\n‘ de novo ’ were included. Secondary search results\nwere also acquired from the references lists of primary search results. The aim of\nthis review was to review SBA cases in the absence of CD. Between 1961 and 2020, a\ntotal of seven case reports of terminal ileal adenocarcinoma mimicking CD in\npatients not previously diagnosed with CD were published. 8–14  Cases of patients\nwith a longstanding history of CD or with well-controlled CD were eliminated. Due to\nits rarity, there is a high probability of misdiagnosing adenocarcinoma as CD when\nthe radiological findings show signs of inflammatory strictures. Moreover,\nclinically, the presentation of SBA and the exacerbation of CD are similar. In a\nretrospective study of 459 SBA cases between 1970 and 2005, the most common symptoms\nof SBA were abdominal pain (43%), nausea and vomiting (16%), fatigue and anaemia\n(15%), gastrointestinal haemorrhage (7%), jaundice (6%) and weight loss\n(3%). 15  Bowel obstruction,\ndiarrhoea and fistula are also well-known findings; however, all of these symptoms\nare also commonly seen in CD. Moreover, symptoms related to malignancy tend to\nimprove with short-term steroid use, which makes the diagnosis of SBA even more\ncomplex. The prognosis of cancer majorly depends on successful early detection;\nhowever, monitoring the response to steroids and awaiting outpatient colonoscopy\ndelays the diagnosis. In a retrospective study, 67% of cases of CD-related SBA were\nfound incidentally at surgery. 16\nTherefore, clinicians should be more cautious when diagnosing CD in patients with a\nlack of long-term response to medical treatment such as corticosteroids.\nFurthermore, the possibility of SBA in the terminal ileum with inflammatory changes\non CT or MRI scans should not be overlooked.\n\nDe novo  small bowel adenocarcinoma (SBA) in the terminal\nileum is the least common of the SBA types.\nChanges in CT and MRI enteroclysis in patients with SBA can look very similar\nto those with CD\nIn the early stages of CD or SBA, thickening and hyperenhancement of the\nmucosa with bowel-wall stenosis can be very difficult to distinguish\nThis makes the diagnosis of terminal ileal adenocarcinoma in the absence of\nCD more difficult due to the high possibility of misdiagnosing it as CD\nInvestigations for CD can delay the diagnosis of SBA, so the possibility of\nSBA should not be overlooked with inflammatory changes in the terminal ileum\non CT or MRI, especially with a lack of long-term response to medical\ntreatments","source_license":"CC-BY-4.0","license_restricted":false}