Steven Polyak

Randomized, controlled trial of standard, large-capacity versus jumbo biopsy forceps for polypectomy of small, sessile, colorectal polyps

BACKGROUND Polypectomy with cold biopsy forceps is a frequently used technique for removal of small, sessile, colorectal polyps. Jumbo forceps may lead to more effective polypectomy because of the larger size of the forceps cup. OBJECTIVE To evaluate the efficiency of cold jumbo biopsy forceps compared with standard forceps for polypectomy of small, sessile, colorectal polyps. DESIGN Randomized, controlled trial. SETTING Outpatient endoscopy center. PATIENTS This study involved 140 patients found to have at least one eligible polyp defined as a sessile polyp measuring ≤6 mm. INTERVENTION Polypectomy with cold biopsy forceps. MAIN OUTCOME MEASUREMENTS Complete visual polyp eradication with one forceps bite. RESULTS In 140 patients, a total of 305 eligible polyps were detected (151 removed with jumbo forceps and 154 with standard forceps). Complete visual eradication of the polyp with one forceps bite was achieved in 78.8% of the jumbo forceps group and 50.7% of the standard forceps group (P < .0001). Biopsies from the polypectomy sites of adenomatous polyps thought to be visually completely eradicated with one bite showed a trend toward a higher complete histologic eradication rate with the jumbo forceps (82.4%) compared with the standard forceps (77.4%), but the difference did not reach statistical significance (P = .62). The withdrawal time for visual inspection of the colon and time to perform polypectomies were significantly shorter in the jumbo forceps group (mean 21.43 vs 18.23 minutes; P = .02). LIMITATIONS Lack of blinding to the type of forceps used. CONCLUSION The jumbo biopsy forceps is superior to the standard forceps in removing small, sessile polyps. ( CLINICAL TRIAL REGISTRATION NUMBER NCT00855790.).

Diagnostic value of noninvasive combined fluorine‐18 labeled fluoro‐2‐deoxy‐D‐glucose positron emission tomography and computed tomography enterography in active Crohn's disease

Background: The role of combined localized positron emission tomography (lPET) and computed tomography enterography (CTe) in Crohns disease is unclear. We examined if this imaging modality using fluorine‐18 labeled‐fluoro‐2‐deoxy‐D‐glucose (FDG) could more effectively identify disease activity. Methods: 52 lPET‐CTe scans were analyzed in this retrospective study. CTe scores and FDG uptake were quantified. Correlations of CTe scores and standard uptake value (SUV) with C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), short Inflammatory Bowel Disease Questionnaire (sIBDq), and Harvey–Bradshaw index (HBI) were estimated using Pearson analysis. Imaging scores were compared to medical outcome by logistics regression model. Results: CTe scores correlated with SUV, but additional abnormal segments of small bowel were not identified. In all, 38 (79%) abnormal CTe segments demonstrated increased FDG uptake with mean SUVmax 4.77; 10 (21%) abnormal CTe segments lacked FDG accumulation, with mean SUVmax 1.27. There was no correlation between SUVmax and CRP, ESR, sIBDq, or HBI. There were no significant differences in clinical indices, biochemical parameters, and presence of multiple abnormal segments between medical responders and uptake were associated with failed medical therapy (P = 0.001). Conclusions: PET scanning added to CTe did not identify additional abnormal segments when compared to CTe alone. Abnormal segments with mucosal enhancement on CTe that did not accumulate FDG were significantly associated with failure of medical therapy. A larger trial is warranted to confirm if combined lPET‐CTe has an important role in the clinical management of stricturing Crohns disease. (Inflamm Bowel Dis 2009;)

Adalimumab for the treatment of Crohn-like colitis and enteritis in glycogen storage disease type Ib

SummaryGlycogen storage disease (GSD) type Ib is a congenital disorder of glycogen metabolism that is associated with neutropenia, neutrophil dysfunction, and an inflammatory bowel disease that mimics a Crohn phenotype. Gastrointestinal inflammation in GSD Ib has been successfully treated with 5-aminosalicylic acid and granulocyte colony-stimulating factor (G-CSF). However, therapeutic options for patients not responding to traditional therapies have been limited owing to untoward effects of glucocorticoids and immunomodulators in this metabolic disorder. Adalimumab is a monoclonal antibody targeting tumour necrosis factor-α that has shown promise for the treatment of patients with Crohn disease. Due to the limited options for treating GSD-associated inflammatory bowel disease, use of adalimumab was attempted in a case unresponsive to aminosalicylate, G-CSF, and antibiotic therapy. Significant clinical and histological improvement was observed in our patient, and the medication was well tolerated.

Antibodies to CBir1 are Associated with Glycogen Storage Disease Type Ib

Objectives: Glycogen storage disease (GSD) type Ib is a congenital disorder of glycogen metabolism that is associated with neutropenia, neutrophil and monocyte dysfunction, and an inflammatory bowel disease (IBD) that mimics a Crohn disease phenotype. The enteric microflora is implicated in the pathogenesis of IBD; however, its role in the development of GSD-associated IBD is unknown. Antibody reactivity to Saccharomyces cerevisiae antibodies (ASCA), Escherichia coli outer membrane porin C (anti-OmpC), and bacterial flagellin (anti-CBir1) have been associated with Crohn disease in the general population, but they have an undetermined association in children and adults with GSD-Ib. Our goal was to examine the association of ASCA, anti-OmpC, and anti-CBir1 with the clinical features of GSD-Ib enterocolitis. Patients and Methods: A retrospective review identified 19 patients with GSD-Ib with or without a known diagnosis of enterocolitis. Radiographic, endoscopic, and serologic data were collected and assays for ASCA, anti-OmpC, and anti-CBir1 obtained. Results: Seven patients had combined radiographic, endoscopic, and histologic evidence of intestinal inflammation; the majority had ileocolonic involvement. Seventeen of 19 (89%) patients had elevated anti-CBir1 levels (6/7 in the IBD group and 11/12 in the no clinical evidence of IBD group). Thirteen of 19 (68%) had elevated anti-OmpC levels (5/7 in the IBD group and 8/12 in the no clinical evidence of IBD group). Eleven of 19 (58%) patients had elevated ASCA IgA levels (4/7 in the IBD group and 7/12 in the no clinical evidence of IBD group). Conclusions: Nearly all of the patients with GSD-Ib had elevated anti-CBir1 levels. The antibody did not differentiate those with and without a diagnosis of GSD-Ib-associated IBD. Seroreactivity to flagellin may represent immune dysfunction rather than active enterocolitis in this patient population. Long-term follow-up of the group without known IBD is required to determine whether these antibodies can predict intestinal inflammation.

Identification of adeno-associated viral vectors suitable for intestinal gene delivery and modulation of experimental colitis.

Effective gene transfer with sustained gene expression is an important adjunct to the study of intestinal inflammation and future therapy in inflammatory bowel disease. Recombinant adeno-associated virus (AAV) vectors are ideal for gene transfer and long-term transgene expression. The purpose of our study was to identify optimal AAV pseudotypes for transduction of the epithelium in the small intestine and colon, which could be used for studies in experimental colitis. The tropism and transduction efficiencies of AAV pseudotypes 1-10 were examined in murine small intestine and colon 8 wk after administration by real-time PCR and immunohistochemistry. The clinical and histopathological effects of IL-10-mediated intestinal transduction delivered by AAVrh10 were examined in the murine IL-10⁻/⁻ enterocolitis model. Serum IL-10 levels and IL-10 expression were followed by ELISA and real-time PCR, respectively. AAV pseudotypes 4, 7, 8, 9, and 10 demonstrated optimal intestinal transduction. Transgene expression was sustained 8 wk after administration and was frequently observed in enteroendocrine cells. Long-term IL-10 gene expression and serum IL-10 levels were observed following AAV transduction in an IL-10-/- model of enterocolitis. Animals treated with AAVrh10-IL-10 had lower disease activity index scores, higher colon weight-to-length ratios, and lower microscopic inflammation scores. This study identifies novel AAV pseudotypes with small intestine and colon tropism and sustained transgene expression capable of modulating mucosal inflammation in a murine model of enterocolitis.

Expression profiling of inflammatory genes identifies differences in the acute and chronic phases of DSS induced colitis: P-254.

lected with isolation of mucus layer fecal colonocytes (MLFC) and total RNA was extracted and processed for miRNA detection. Total RNA was processed for reverse transcription using miRNA reverse transcription kit (Applied Biosystems) and assayed for specific miRNAs using individual Taqman miRNA assays namely, miR-142-3p, miR-21, miR-34a, miR-146b, miR-148b-3p and miR-494 (Applied Biosystems) using manufacturer’s instructions. RESULTS: The six miRNAs tested had been previously demonstrated to be upregulated in colonic field carcinogenesis. Out of the miRNAs tested, miR-34a was found to be significantly induced in HT-29 cells.(4.8 fold induction, p1⁄40.02). We next both in the fecal colonocytes from C. rodentium infected mice and noted a dramatic induction (7.2 fold, p<0.05). To demonstrate the relevance to colon carcinogenesis, we used gold-standard model, the azoxymethane-treated rat (a carcinogen induced model). We noted that at premalignant time points there was a marked increase in mucus layer fecal colonocytes (4.2 to 6.2 fold, p<0.05) CONCLUSION: We present herein the first data that fecal miR 34a may be a marker for neoplastic risk of in both an inflammation model and a well-validated CRC models. Importantly, miR 34a is regulated by p53, one of the earliest events in colitis-induced CRC (found in flat dysplasia or histologically normal mucosa of patients harboring dysplasia). Thus, while confirmation for IBD dysplasia will be performed with standard DSS or transgenic (IL10 knockouts etc.) models, this work provides a powerful proof of concept that miR34a may serve as a biomarker for colitis-induced CRC. Furthermore, the development of mucus layer fecal colonocytes as a marker of field carcinogenesis may represent significant advance in the surveillance for IBD-related neoplasia.