OsmoPrep-associated Gastritis: A Histopathologic Mimic of Iron Pill Gastritis and Mucosal Calcinosis.

We have identified 8 cases of gastritis characterized by the presence of purple to black granular deposits in the superficial mucosa associated with marked reactive epithelial changes. In each case, the patient had taken OsmoPrep, a tablet form of sodium phosphate used for bowel preparation just before upper endoscopy and had undergone concurrent colonoscopy. Endoscopic findings ranged from normal gastric mucosa to severe inflammation, congestion, and friability. No other gastrointestinal sites were noted to contain the deposits or show similar mucosal injury. On initial histologic review, the deposits raised the differential diagnosis of elemental iron and mucosal calcinosis. However, none of the patients was noted to be taking iron supplements, and none had a history of renal disease or other cause of calcium dysmetabolism. Histochemical stains revealed the deposits were negative on Perls' iron stain (8/8 cases), positive on von Kossa stain (7/8 cases), and negative on Alizarin Red stain (8/8 cases)-a histochemical profile compatible with sodium phosphate but inconsistent with mucosal calcium. A crushed OsmoPrep tablet was subjected to processing and demonstrated similar histologic features and histochemical profile. In addition, biopsies of 20 consecutive patients who did not take OsmoPrep and who underwent concurrent endoscopy and colonoscopy were reviewed, and no deposits with similar histochemical profile were identified. In summary, we have characterized a unique form of gastritis associated with OsmoPrep use. Attention to clinical history and use of a select panel of histochemical stains allow for accurate diagnosis.

Analysis of Gut Microbiome and Diet Modification in Patients with Crohn's Disease.

OBJECTIVE: The human intestine harbors trillions of commensal microbes that live in homeostasis with the host immune system. Changes in the composition and complexity of gut microbial communities are seen in inflammatory bowel disease (IBD), indicating disruption in host-microbe interactions. Multiple factors including diet and inflammatory conditions alter the microbial complexity. The goal of this study was to develop an optimized methodology for fecal sample processing and to detect changes in the gut microbiota of patients with Crohn's disease receiving specialized diets. DESIGN: Fecal samples were obtained from patients with Crohn's disease in a pilot diet crossover trial comparing the effects of a specific carbohydrate diet (SCD) versus a low residue diet (LRD) on the composition and complexity of the gut microbiota and resolution of IBD symptoms. The gut microbiota composition was assessed using a high-density DNA microarray PhyloChip. RESULTS: DNA extraction from fecal samples using a column based method provided consistent results. The complexity of the gut microbiome was lower in IBD patients compared to healthy controls. An increased abundance of Bacteroides fragilis (B. fragilis) was observed in fecal samples from IBD positive patients. The temporal response of gut microbiome to the SCD resulted in an increased microbial diversity while the LRD diet was associated with reduced diversity of the microbial communities. CONCLUSION: Changes in the composition and complexity of the gut microbiome were identified in response to specialized carbohydrate diet. The SCD was associated with restructuring of the gut microbial communities.

Dysregulation of anti-inflammatory annexin A1 expression in progressive Crohns Disease.

BACKGROUND: Development of inflammatory bowel disease (IBD) involves the interplay of environmental and genetic factors with the host immune system. Mechanisms contributing to immune dysregulation in IBD are not fully defined. Development of novel therapeutic strategies is focused on controlling aberrant immune response in IBD. Current IBD therapy utilizes a combination of immunomodulators and biologics to suppress pro-inflammatory effectors of IBD. However, the role of immunomodulatory factors such as annexin A1 (ANXA1) is not well understood. The goal of this study was to examine the association between ANXA1 and IBD, and the effects of anti-TNF-α, Infliximab (IFX), therapy on ANXA1 expression. METHODS: ANXA1 and TNF-α transcript levels in PBMC were measured by RT PCR. Clinical follow up included the administration of serial ibdQs. ANXA1 expression in the gut mucosa was measured by IHC. Plasma ANXA1 levels were measured by ELISA. RESULTS: We found that the reduction in ANXA1 protein levels in plasma coincided with a decrease in the ANXA1 mRNA expression in peripheral blood of IBD patients. ANXA1 expression is upregulated during IFX therapy in patients with a successful intervention but not in clinical non-responders. The IFX therapy also modified the cellular immune activation in the peripheral blood of IBD patients. Decreased expression of ANXA1 was detected in the colonic mucosa of IBD patients with incomplete resolution of inflammation during continuous therapy, which correlated with increased levels of TNF-α transcripts. Gut mucosal epithelial barrier disruption was evident by increased plasma bacterial 16S levels. CONCLUSION: Loss of ANXA1 expression may support inflammation during IBD and can serve as a biomarker of disease progression. Changes in ANXA1 levels may be predictive of therapeutic efficacy.

Magnetic endoscope imaging (ScopeGuide) elucidates the mechanism of action of the pain-alleviating impact of water exchange colonoscopy - attenuation of loop formation.

BACKGROUND: The explanation why water exchange colonoscopy produces a significant reduction of pain during colonoscopy is unknown. A recent editorial recommended use of magnetic endoscope imaging (MEI) to elucidate the explanation. OBJECTIVE: In unselected patients to show that MEI documents less frequent loop formation when water exchange is used. DESIGN: Observational, performance improvement. SETTING: Veterans Affairs outpatient endoscopy. PATIENTS: Routine colonoscopy cases. INTERVENTIONS: Colonoscopy using air or water exchange method was performed as previously described. The MEI equipment (ScopeGuide, Olympus) with built-in magnetic sensors displays the configuration of the colonoscope inside the patient. During sedated colonoscopy the endoscopist was blinded to the ScopeGuide images which were recorded and subsequently reviewed. MAIN OUTCOME MEASURES: Loop formation based on a visual guide provided by Olympus. RESULTS: There were 41 and 32 cases in the water exchange and air group, respectively. The sigmoid N loop was most common, followed by the sigmoid alpha loop, and exaggeration of scope curvature at the splenic flexure/transverse colon. Of these, 20/32 vs. 9/41 patients (p=0.0007) had sigmoid looping, and 17/32 vs. 9/41 patients (p=0.0007) had sigmoid/splenic looping when the scope tip was in the transverse colon, in the air and water exchange group, respectively. LIMITATIONS: Colonoscopy method was not blinded and non randomized. CONCLUSION: MEI data objectively demonstrated significantly fewer loops during water exchange colonoscopy, elucidating its mechanism of pain alleviation - attenuation of loop formation. Since MEI feedback enhances cecal intubation by trainees, the role of MEI combined water exchange in speeding up trainee learning curves deserves further evaluations.

Hepatosplenic T-cell lymphoma and inflammatory bowel disease.

OBJECTIVE: This article reviews the current literature and knowledge about hepatosplenic T-cell lymphoma (HSTCL), providing an overview of the clinical features, a description of its pathology and immunophenotypic traits in relation to other lymphomas. In addition, we explore the history of reported cases of hepatosplenic T-cell lymphoma in relation to the possible existence of a causal relationship between infliximab use and HSTCL. The treatments for HSTCL will be briefly addressed. METHODS: A comprehensive literature search using multiple databases was performed. Keyword search phrases including "lymphoma," "hepatosplenic T-cell lymphoma," "Inflammatory bowel disease," "6-mercaptopurine," and "infliximab" were used in various combinations. In addition references from published papers were reviewed as well. RESULTS: There are over 200 reported cases of HSTCL. Only 22 cases of hepatosplenic T-cell lymphoma are associated with IBD treatment. Clinicians usually reserve immunomodulators and biologics for moderate to severe IBD cases. The ultimate goal of therapy is to control inflammation and therefore allow mucosal healing. IBD patients demonstrating mucosal healing are less likely to undergo surgery and experience complications related to their disease. We manipulate the immune system with corticosteroids, immunomodulators, and biologics, therefore causing bone marrow suppression. With bone marrow suppression, malignant degeneration may begin through selective uncontrolled cell proliferation, initiating HSTCL development in the genetically susceptible. CONCLUSION: Hepatosplenic T-cell lymphoma is a rare disease, often with a poor outcome. With the increasing number of reported cases of HSTCL linked to the use of infliximab, adalimumab, and AZA/6-MP, there appears to be an undeniable association of HSTCL development with the use of these agents. This risk is unquantifiable. When considering the rarity of cases and the multiple complications with uncontrolled disease, however, the benefit of treatment far outweighs the risk.