NSAID enteropathy: appearance at CT and MR enterography in the age of multi-modality imaging and treatment.

CT and MR enterography and capsule endoscopy are increasingly used as routine diagnostic tests for patients with potential small bowel disorders and obscure gastrointestinal bleeding. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used drugs that disrupt prostaglandin synthesis and result in a variety of localized complications within the small bowel ranging from ulcer formation to characteristic circumferential strictures, or diaphragms. NSAID enteropathy encompasses this spectrum of acute and chronic inflammatory sequelae, and is associated with typical findings at capsule endoscopy and surgery. Herein we review the typical clinical presentation of NSAID enteropathy, in addition to its endoscopic appearances, focusing on imaging findings at cross-sectional enterography. Multiple, short-segment strictures are the hallmarks of imaging diagnosis. Strictures may have minimal hyperenhancement or wall thickening, but these findings are typically symmetric and circumferential with respect to the bowel lumen. Multifocal Crohn's strictures, and occasionally radiation-induced strictures or adhesions, will mimic NSAID diaphragms. Multi-phase or multi-sequence imaging at CT and MR enterography increase diagnostic confidence in stricture presence. Strategies for subsequent workup and therapy after enterography are also discussed. Given the frequent use of NSAIDs and typical appearance of these strictures, knowledge of characteristic imaging findings can be particularly useful when evaluating patients with anemia and recurrent small bowel obstruction.

Multiple jejunal cancers resulting from combination of germline APC and MLH1 mutations.

Double heterozygotes for mutations in APC and a DNA mismatch repair gene are extremely rare. We report on an individual who had truncating mutations in APC and MLH1 whose clinical presentation initially resembled Familial Adenomatous Polyposis but then emerged as a novel phenotype with multiple jejunal carcinomas. We have reviewed the relevant literature on double heterozygotes and based on what has been reported to date, this phenotype was not anticipated. It may be useful for clinicians to be aware of this observation as clinical screening guidelines are proposed for such individuals.

The pathogen recognition receptor NOD2 regulates human FOXP3+ T cell survival.

The expression of pathogen recognition receptors in human FOXP3+ T regulatory cells is established, yet the function of these receptors is currently obscure. In the process of studying the function of both peripheral and lamina propria FOXP3+ lymphocytes in patients with the human inflammatory bowel disease Crohn's disease, we observed a clear deficiency in the quantity of FOXP3+ lymphocytes in patients with disease-associated polymorphisms in the pathogen recognition receptor gene NOD2. Subsequently, we determined that the NOD2 ligand, muramyl dipeptide (MDP), activates NF-kappaB in primary human FOXP3+ T cells. This activation is functionally relevant, as MDP-stimulated human FOXP3+ T cells are protected from death receptor Fas-mediated apoptosis. Importantly, apoptosis protection was not evident in MDP-stimulated FOXP3+ T cells isolated from a patient with the disease-associated polymorphism. Thus, we propose that one function of pathogen recognition receptors in human T regulatory cells is the protection against death receptor-mediated apoptosis in a Fas ligand-rich environment, such as that of the inflamed intestinal subepithelial space.

Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states.

BACKGROUND: Colon cancer arises from the accumulation of multiple genetic and epigenetic alterations to normal colonic tissue. microRNAs (miRNAs) are small, non-coding regulatory RNAs that post-transcriptionally regulate gene expression. Differential miRNA expression in cancer versus normal tissue is a common event and may be pivotal for tumor onset and progression. METHODS: To identify miRNAs that are differentially expressed in tumors and tumor subtypes, we carried out highly sensitive expression profiling of 735 miRNAs on samples obtained from a statistically powerful set of tumors (n = 80) and normal colon tissue (n = 28) and validated a subset of this data by qRT-PCR. RESULTS: Tumor specimens showed highly significant and large fold change differential expression of the levels of 39 miRNAs including miR-135b, miR-96, miR-182, miR-183, miR-1, and miR-133a, relative to normal colon tissue. Significant differences were also seen in 6 miRNAs including miR-31 and miR-592, in the direct comparison of tumors that were deficient or proficient for mismatch repair. Examination of the genomic regions containing differentially expressed miRNAs revealed that they were also differentially methylated in colon cancer at a far greater rate than would be expected by chance. A network of interactions between these miRNAs and genes associated with colon cancer provided evidence for the role of these miRNAs as oncogenes by attenuation of tumor suppressor genes. CONCLUSION: Colon tumors show differential expression of miRNAs depending on mismatch repair status. miRNA expression in colon tumors has an epigenetic component and altered expression that may reflect a reversion to regulatory programs characteristic of undifferentiated proliferative developmental states.

Adequacy of endoscopic ultrasound core needle biopsy specimen of nonmalignant hepatic parenchymal disease.

BACKGROUND & AIMS: The adequacy and diagnostic yield of hepatic parenchymal disease Trucut biopsy have not been determined. Therefore, our aim was to determine the adequacy of endoscopic ultrasound (EUS)-guided Trucut liver biopsy for histopathologic evaluation to include the number of complete portal tracts contained per millimeter of acquired tissue. METHODS: A single institution retrospective review was made of 9 prospectively identified patients who underwent a transgastric left liver lobe EUS-guided Trucut biopsy during a 36-month period. RESULTS: Adequate diagnostic material, to include complete portal tract number evaluation (median, 7) and connective tissue staining, was acquired to establish a histopathologic diagnosis in all 9 cases. Sixty-three complete portal tracts were established, resulting in 0.4 portal tracts per millimeter of tissue acquired. Findings established by EUS Trucut left liver lobe biopsy included mild steatosis (n = 4), cryptogenic cirrhosis (n = 2), chronic ductopenic biliary tract disease (n = 1), portal fibrosis with ductular proliferation (n = 1), and alcoholic cirrhosis with hemosiderosis (n = 1). CONCLUSIONS: EUS-guided Trucut left liver lobe biopsy yields suitable aggregate tissue for diagnostic purposes to establish the presence of chronic liver disease.

Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study.

BACKGROUND & AIMS: The revised Bethesda guidelines for Lynch syndrome recommend microsatellite instability (MSI) testing all colorectal cancers in patients diagnosed before age 50 years and colorectal cancers diagnosed in patients between ages 50 and 59 years with particular pathology features. Our aim was to identify pathology and other features that independently predict high MSI (MSI-H). METHODS: Archival tissue from 1098 population-based colorectal cancers diagnosed before age 60 years was tested for MSI. Pathology features, site, and age at diagnosis were obtained. Multiple logistic regression was performed to determine the predictive value of each feature, as measured by an odds ratio (OR), from which a scoring system (MsPath) was developed to estimate the probability a colorectal cancer is MSI-H. RESULTS: Fifteen percent of tumors (162) were MSI-H. Independent predictors were tumor-infiltrating lymphocytes (OR, 9.1; 95% confidence interval [CI], 5.9-14.1), proximal subsite (OR, 4.7; 95% CI, 3.1-7.3), mucinous histology (OR, 2.8; 95% CI, 1.7-4.8), poor differentiation (OR, 1.9; 95% CI, 1.2-3.1), Crohn's-like reaction (OR, 1.9; 95% CI, 1.2-2.9), and diagnosis before age 50 years (OR, 1.9; 95% CI, 1.3-2.9). MsPath score >or=1.0 had a sensitivity of 93% and a specificity of 55% for MSI-H. CONCLUSIONS: The probability an individual colorectal cancer is MSI-H is predicted well by the MsPath score. There is little value in testing for DNA mismatch repair loss in tumors, or for germline mismatch repair mutations, for colorectal cancers diagnosed in patients before age 60 years with an MSPath score <1 (approximately 50%). Pathology can identify almost all MSI-H colorectal cancers diagnosed before age 60 years.