Focal loss of mural stratification as a radiological predictor for small bowel adenocarcinoma in Crohn's disease.

AIM: Patients with Crohn's disease (CD) are at higher risk of small bowel adenocarcinoma (SBA). We aimed to identify radiological predictors of SBA in CD. METHODS: We conducted a retrospective case-control study at two tertiary inflammatory bowel disease centers and identified CD patients diagnosed with SBA between 2003 and 2019. Patients were matched with up to four controls. Pre-operative imaging (magnetic resonance imaging (MRI) or computed tomography (CT)) were reviewed by three gastrointestinal radiologists. RESULTS: Nineteen patients with CD-associated SBA with a mean age of 54.9 and 32 matched controls were included. Mean length of small bowel involvement was 216 (± 188) mm in the SBA group versus 156 (± 167) mm in the control group (p = 0.76). Only 11.8 % of cases had a diagnosis of SBA made preoperatively. In univariate analysis, focal loss of mural stratification (odds ratio [OR], 11; 95%CI, 2.43-49.5, p = 0.002), and wall thickening (OR, 1.32; 95%CI, 1.05-1.66, p = 0.02) were significantly associated with SBA. After adjustment, focal loss of mural stratification was the only independent risk factor (OR, 11; 95 % CI, 2.43-49.5, p = 0.002). CONCLUSIONS: Focal loss of mural stratification was identified as a predictor of CD-associated SBA, which should be described in imaging reports and further validated.

Small Intestinal Adenocarcinomas Arising in Enteritis Cystica Profunda With Metaplasia: A Report of 2 Cases.

Enteritis cystica profunda (ECP) is an uncommon benign condition arising after mucosal damage. We describe 2 cases of small intestinal adenocarcinomas associated with ECP at the distal ileum, one in a background of active Crohn ileitis (case 1), the other 22 years after pelvic radiation therapy (case 2). Both patients presented with small bowel obstruction and received ileocectomy. Macroscopic examination identified an indurated/strictured area in the distal ileum. Histologically, both cases showed a low-grade tubuloglandular adenocarcinoma arising in a background of chronic ischemic stricture and ECP lined by flat cuboidal cells with mild cytologic atypia resembling pancreatobiliary-type epithelium. There was no conventional dysplasia in the surface or adjacent mucosa. Immunohistochemically, both ECP with metaplasia and invasive carcinomas were diffusely positive for CK7 and CK19, while focally positive for CDX2 or CK20. Both cases showed normal wild-type p53 expression. Case 2 was also mismatch repair protein proficient, with membranous ß-catenin staining, and retained nuclear SMAD4 expression. In summary, the 2 cases uniquely exhibits "enteritis-metaplasia-carcinoma" sequence, which has not been reported before. This process appears to bypass conventional dysplasia, be slow and indolent, independent of p53, APC/ß-catenin, and SMAD4/TGFß signaling pathways.

Crohn's disease associated adenocarcinoma of ileocaecal region: a miscalculated approach.

Adenocarcinoma of the bowel is a dreadful sequelae of inflammatory bowel disease that can be difficult to diagnose and has been shown to have poor prognosis. The diagnosis is often made on histopathological examination of the resected specimen for what is suspected to be an exacerbation of the underlying intestinal Crohn's. A 39-year-old woman who was being treated for small bowel Crohn's disease for 4 years presented with features of intermittent intestinal obstruction that was refractory to medical therapy. A contrast CT of the abdomen was suggestive of ileocaecal Crohn's disease, and colonoscopy revealed a stricture at proximal transverse colon with multiple superficial ulcers. She underwent a mesentery sparing right hemicolectomy and had an uneventful recovery. The biopsy, however, was reported to be moderately differentiated adenocarcinoma stage T3N0 with a harvest of four pericolic nodes. Adjuvant chemotherapy was advised, which she deferred. Ten months later, she presented to the emergency room with features of intestinal obstruction. Contrast CT of the abdomen showed thickening at the anastomotic site with intestinal obstruction. On exploratory laparotomy, tumour recurrence was noted at the site of the anastomosis and diffuse peritoneal metastasis. A palliative diversion ileostomy was done due to inoperable obstructing disease. She was then given palliative therapy and subsequently succumbed to the illness. The inclusion of mesentery with the resected specimen in Crohn's disease has been a debate over many years. Since the preoperative diagnosis of carcinoma of the bowel in Crohn's disease is challenging, all ileocolic resections should be radical as done in oncological resections. This would yield better oncological safety and may improve survival rates.

IGF2 drives formation of ileal neuroendocrine tumors in patients and mice.

By the strictest of definitions, a genetic driver of tumorigenesis should fulfill two criteria: it should be altered in a high percentage of patient tumors, and it should also be able to cause the same type of tumor to form in mice. No gene that fits either of these criteria has ever been found for ileal neuroendocrine tumors (I-NETs), which in humans are known for an unusual lack of recurrently mutated genes, and which have never been detected in mice. In the following report, we show that I-NETs can be generated by transgenic RT2 mice, which is a classic model for a genetically unrelated disease, pancreatic neuroendocrine tumors (PNETs). The ability of RT2 mice to generate I-NETs depended upon genetic background. I-NETs appeared in a B6AF1 genetic background, but not in a B6 background nor even in an AB6F1 background. AB6F1 and B6AF1 have identical nuclear DNA but can potentially express different allelic forms of imprinted genes. This led us to test human I-NETs for loss of imprinting, and we discovered that the IGF2 gene showed loss of imprinting and increased expression in the I-NETs of 57% of patients. By increasing IGF2 activity genetically, I-NETs could be produced by RT2 mice in a B6 genetic background, which otherwise never developed I-NETs. The facts that IGF2 is altered in a high percentage of patients with I-NETs and that I-NETs can form in mice that have elevated IGF2 activity, define IGF2 as the first genetic driver of ileal neuroendocrine tumorigenesis.

Neuroendocrine Tumors of Meckel's Diverticula: Rare but Fare Well.

Neuroendocrine tumors (NETs) are the most common malignancy arising in Meckel's diverticula (MDs). To date, there are no large series characterizing these tumors. The National Cancer Database was queried for patients with MD NETs (n = 162) from 2004 to 2014. Patient and tumor characteristics as well as outcomes were analyzed. MD NETs were more common in men (72.8%) at a median age of 62 years; 95.1 per cent of patients were white. All patients underwent surgery. Clinical M0 disease was present in 97.4 per cent of patients, and 88.2 per cent of tumors were well differentiated. Lymphovascular invasion was present in 13.2 per cent. Most (60.4%) tumors were less than 10 mm. Lymphadenectomy was performed in 32.9 per cent of patients, with 52.1 per cent of these found to have metastatic lymph node disease. Although most MD NETs are well differentiated, smaller than 10 mm, and do not have lymphovascular invasion, lymph node metastases are commonly found, suggesting that mesenteric lymphadenectomy with adequate resection of the small bowel may be necessary for adequate staging and disease clearance.

Malignant melanoma arising from an end ileostomy.

A 65-year-old woman with a history of proctocolectomy and end ileostomy for ulcerative colitis was referred to our clinic with a slowly growing mass around her ileostomy. She did not report any systemic symptoms. On examination, an exophytic mass was observed around her ileostomy and hard lymph nodes palpated in her groins bilaterally. Punch biopsy of the lesion established a diagnosis of invasive melanoma. Positron emission tomography revealed regional metastatic lymphadenopathy in the right axilla and both groins. There was no evidence of distant metastatic disease. The patient then underwent wide local excision of her ileostomy with bowel resection and ileostomy re-siting, bilateral complete ilioinguinal lymphadenectomy and a right Level III axillary dissection. She is doing well postoperatively and receiving adjuvant systemic therapy with BRAF and MEK inhibitors, now 17 months later with no signs of recurrent disease.

Meckel's diverticulum in the adult: surgical treatment.

Introduction: Management of asymptomatic Meckel's diverticulum (MD) incidentally discovered in adults remains controversial. The aim of this study was to determine if incidental diverticula should be removed. Materials and methods: We reviewed a consecutive series of patients surgically managed from January 1994 to December 2016. Patients were divided into two groups according to symptomatic or asymptomatic diverticula, and characteristics were compared. Results: The study included 66 patients: 30 in the symptomatic group (45%) and 36 in the incidental group (55%). We found 12 females (18.2%), and the ratio male:female was higher in the symptomatic group (14:1 vs. 2.6:1). Patients in the symptomatic group were significantly younger: 41.7 ± 18.1 vs. 54.7 ± 19.8 years (p = .007). MD in the symptomatic group tended to be longer (3.8 ± 1.9 vs. 2.6 ± 0.9 cm; p = .003). A MD-associated malignancy was present in three patients (4.5%), all neuroendocrine tumours. Major postoperative complications occurred in 6.6% of symptomatic patients and 0% within the incidental group, without specific morbidity related to prophylactic surgery. No mortality was observed. Conclusion: Resection of incidentally found Meckel's diverticulum can be made because of benefits outweigh the risks in this high-risk area for cancer.

Small bowel adenocarcinoma in a patient with a 5-year history of untreated Crohn's disease: a case report.

AIM: Complication of Crohn's disease (CD) of the small intestine is small bowel adenocarcinoma (SBA). A lot of studies on Crohn's disease have estimated the increased relative risk of small bowel carcinoma compared to the general population. In clinical settings, it is difficult to detect SBA in CD, therefore most of cases are diagnosed after surgery for strictures without suspicion of malignancy. CASE REPORT: The present case concerns a 48-year-old man with a suspicious 5-year history of untreated chronic inflammatory bowel disease. The patient was admitted to our unit with persistent abdominal pain, 20 kg weight loss and intestinal obstruction, confirmed at CT scans. It was performed an emergency laparotomy, terminal ileus was resected and intestinal continuity was restored. Histological examination revealed a poorly differentiated adenocarcinoma. DISCUSSION: The risk factors of SBA include long-standing and extensive Crohn's disease, young age, male sex, smoke, early onset, complications such as strictures and fistulas The most common clinical presentation of small bowel carcinoma in Crohn's disease is intestinal obstruction accompanied by wheight loss. The diagnosis is very difficult because imaging techniques may not be able to differentiate areas of small bowel carcinomas from benign fibrotic or acute inflammatory strictures. CONCLUSION: Small bowel adenocarcinoma is a rare disease but this evenience must be considered in patients with strictures for Crohn's disease. Preoperative diagnosis is still highly challenging despite significant radiological and endoscopic progress.

A case of Crohn's disease complicated with simultaneous double cancers of the small bowel.

A case of Crohn's disease complicated with simultaneous double cancers of the small bowel is reported. The patient is a 66-year-old man who had suffered from Crohn's disease for 20 years. He underwent surgery to identify the source of repeated episodes of intestinal obstruction. Two short segments of strictures and proximal dilatations were found in the distal ileum. Therefore, we performed an en bloc resection of the two stenotic sections instead of strictureplasty. Histological examination of the resected specimen revealed not only Crohn's disease but also a well-differentiated adenocarcinoma within each of the two strictures. One had invaded to the muscular layer and the other to the subserosal layer. In cases of Crohn's disease with longstanding stenosis, the probability of carcinoma should be considered.

Hepatoid adenocarcinoma arising from heterotopic pancreas of the ileum: A case report.

INTRODUCTION: Hepatoid adenocarcinoma (HAC) is a rare neoplasm with a striking morphologic similarity to hepatocellular carcinoma. The most common sites of HAC are the stomach, lung, and pancreas. CASE REPORT: Here we report a rare case of HAC arising from the heterotopic pancreas (Heinrich type II) in the ileum with lymph node metastasis. A 56-year-old man was admitted to our hospital presenting with bloody stools under no obvious predisposing causes. The colonoscopy and the gastroscopy showed no pathological findings. A computed tomography scan showed an intussusception of ileum. Then partial resection of ileum was performed with end-to-end anastomosis and appendectomy. Histopathological examination showed a malignant transformation of heterotopic pancreas (Heinrich type II) in the ileum. We made the diagnosis of HAC based on clinical pathological features and immunochemical staining. The patient received chemotherapy and died 9 months later. CONCLUSION: To our best knowledge, this is the first reported case of HAC originated from a heterotopic pancreas in the ileum. The clinical pathological features and immunochemical staining are important for correct diagnosis of HAC.

Cancer arising from the remnant mucosa of the ileoanal anastomosis leading to pouchectomy.

Ileal pouch-related adenocarcinoma remains a rarity; thus, guidelines on treatment are currently lacking. We present this case of a 54-year-old man who underwent restorative proctocolectomy with stapled ileal pouch-anal anastomosis formation for familial adenomatous polyposis during the 1980s. Despite undergoing annual surveillance endoscopy, the patient was noted to be anaemic and passing fresh blood per anus Endoscopy and radiological investigation revealed the presence of a pouch-related adenocarcinoma. This was subsequently treated with short-course radiotherapy and pouch excision. The patient remains well until now and will follow six-monthly surveillance protocols with a transition to annual surveillance after 2 years.

Mesenteric tumor due to chronic anisakiasis.

Intestinal anisakiasis is a rare parasitic disease and difficult to diagnose due to symptoms are not specific, so it is considered an underdiagnosed disease. The clinical suspicion with a correct diagnosis of anisakiasis allows the establishment of a correct treatment; in most cases, the resolution is possible with conservative treatment, avoiding unnecessary surgery to the preoperative differential diagnosis of acute abdomen. We report the case of apatient who required urgent surgery secondary to an exacerbation of chronic anisakiasis.

Endoscopic submucosal dissection to treat ileal high-grade dysplasia after ileoanal anastomosis for familial adenomatous polyposis: report of a case.

Restorative proctocolectomy has become the most common surgical option for familial adenomatous polyposis patients, based on the premise that the technique yields good functional results and reduces colorectal cancer risk. However, several adenomas may develop in the pouch mucosa in later years, and even cancer (at the anastomosis or in the pouch mucosa) has been reported. Endoscopic submucosal dissection (ESD) would then be indicated, even if severe fibrosis extended into the submucosal layer. Endoscopic resection of an ileal tumor from the thin wall of the ileum carries a high-risk of perforation. Our present case demonstrates the successful use of ESD to treat an ileal neoplasm, a technically difficult lesion with a high-risk of complications.

Crohn enteritis-associated small bowel adenocarcinomas exhibit gastric differentiation.

Primary small bowel adenocarcinoma is rare. Although generally similar to colonic adenocarcinoma, some small bowel adenocarcinomas exhibit unique morphologic features, particularly those arising in association with Crohn disease. In this study, 15 sporadic small bowel adenocarcinomas and 11 Crohn enteritis-associated small bowel adenocarcinomas were examined for histology and immunohistochemical profile including cytokeratins (CK) 7 and 20, intestinal markers CDX2 and MUC2, and gastric epithelial markers MUC5AC and MUC6. We found that Crohn enteritis-associated small bowel adenocarcinomas frequently resemble gastric tubular adenocarcinoma histologically. In addition, when compared to sporadic small bowel adenocarcinoma, the former expressed MUC5AC and MUC6 with much higher frequency (82% vs. 7% and 73% vs. 0%, respectively). Ten of 11 Crohn enteritis-associated small bowel adenocarcinomas (91%) were positive for at least one gastric-type marker (MUC5AC or MUC6). Expression of CK7 was also more frequent in Crohn enteritis-associated small bowel adenocarcinoma (73% versus 27%) while expression of CK20 was less frequent (64% vs. 100%). There was no difference between sporadic and Crohn enteritis-associated small bowel adenocarcinoma in expression of CDX2 (100% vs. 91%) and MUC2 (93% vs. 73%). These observations suggest that there is a difference in the morphologic and immunohistochemical characteristics of sporadic versus Crohn enteritis-associated small bowel adenocarcinoma, particularly in their expression of gastric-type mucin. The findings also suggest that gastric differentiation in Crohn enteritis-associated small bowel adenocarcinoma is related to gastric metaplasia, a common phenomenon in Crohn disease.

Non-colorectal intestinal tract carcinomas in inflammatory bowel disease: results of the 3rd ECCO Pathogenesis Scientific Workshop (II).

Patients with inflammatory bowel diseases (IBD) have an excess risk of certain gastrointestinal cancers. Much work has focused on colon cancer in IBD patients, but comparatively less is known about other more rare cancers. The European Crohn's and Colitis Organization established a pathogenesis workshop to review what is known about these cancers and formulate proposals for future studies to address the most important knowledge gaps. This article reviews the current state of knowledge about small bowel adenocarcinoma, ileo-anal pouch and rectal cuff cancer, and anal/perianal fistula cancers in IBD patients.