James F. Marion

Chromoendoscopy-targeted biopsies are superior to standard colonoscopic surveillance for detecting dysplasia in inflammatory bowel disease patients: a prospective endoscopic trial.

OBJECTIVES:Patients with extensive, longstanding chronic ulcerative or Crohns colitis face greater risks of developing colorectal cancer. Current standard surveillance relies on detecting dysplasia using random sampling at colonoscopy but may fail to detect dysplasia in many patients. Dye spraying techniques have been reported to aid in detecting otherwise subtle mucosal abnormalities in the setting of colitis. We prospectively compared dye-spray technique using methylene blue to standard colonoscopic surveillance in detecting dysplasia.METHODS:One hundred fifteen patients were referred to the Chromoendoscopy Study Group and prospectively screened for the study. One hundred two (64 M, 38 F) (79 UC 23 CC) patients meeting the inclusion criteria were enrolled. Following a standard bowel preparation, each patient was examined using standard office endoscopic equipment by three methods: (a) standard surveillance colonoscopy with four random biopsies every 10 cm (for a total of at least 32 samples); (b) a targeted biopsy protocol; and finally (c) methylene blue (0.01%) dye spray was segmentally applied throughout the colon and any pit-pattern abnormality or lesion rendered visible by the dye spray was targeted and biopsied. Each patient had a single examination, which included two passes of the colonoscope. Specimens were reviewed in a blinded fashion by a single gastrointestinal pathologist. The three methods were then compared with each patient serving as his or her own control.RESULTS:Targeted biopsies with dye spray revealed significantly more dysplasia (16 patients with low grade and 1 patient with high grade) than random biopsies (3 patients with low-grade dysplasia) (P = 0.001) and more than targeted nondye spray (8 patients with low-grade and 1 patient with high-grade dysplasia) (P = 0.057). Targeted biopsies with and without dye spray detected dysplasia in 20 patients compared with 3 using Method (a) (P = 0.0002, two-tailed exact McNemars Test). There were no adverse events.CONCLUSIONS:Colonoscopic surveillance of chronic colitis patients using methylene blue dye-spray targeted biopsies results in improved dysplasia yield compared to conventional random and targeted biopsy methods. Accordingly, this technique warrants incorporation into clinical practice in this setting and consideration as a standard of care for these patients. The value of multiple random biopsies as a surveillance technique should be revisited.

Once-Daily Dosing of Delayed-Release Oral Mesalamine (400-mg Tablet) Is as Effective as Twice-Daily Dosing for Maintenance of Remission of Ulcerative Colitis

BACKGROUND & AIMS The practice of dosing mesalamines in divided doses for the treatment of ulcerative colitis (UC) began with sulfasalazine and was driven by sulfapyridine toxicity. This convention and the assumption that dosing multiple times a day is necessary to treat UC had not been challenged until recently. This study was conducted to determine the efficacy and safety of once-daily dosing of delayed-release mesalamine (Asacol 400-mg tablets) compared with twice-daily dosing for maintaining remission in UC patients. METHODS A multicenter, randomized, investigator-blinded, 12-month, active-control trial was conducted to assess the noninferiority of delayed-release mesalamine 1.6-2.4 g/day administered once daily compared with twice daily in patients with mild-to-moderate UC currently in clinical remission. The primary end point was maintenance of clinical remission at month 6. RESULTS A total of 1023 patients were randomized and dosed. The primary objective of noninferiority was met. At month 6, 90.5% of patients receiving once-daily dosing had maintained clinical remission, compared with 91.8% of patients receiving twice-daily dosing (95% confidence interval for twice daily - once daily, -2.3 to 4.9). At month 12, 85.4% of patients receiving once-daily dosing had maintained clinical remission, compared with 85.4% of patients receiving twice-daily dosing (95% confidence interval for twice daily - once daily, -4.6 to 4.7). Both regimens had low rates of withdrawals as a result of adverse events and serious adverse events. CONCLUSIONS Once-daily dosing of delayed-release mesalamine at doses of 1.6-2.4 g/day was shown to be as effective as twice-daily dosing for maintenance of clinical remission in patients with UC.

Fistula response to methotrexate in Crohn's disease: a case series.

Background : Controlled trials have demonstrated the efficacy of methotrexate in the induction and maintenance of remission in luminal Crohns disease; however, its effect on fistulizing disease is unknown.

Chromoendoscopy Is More Effective Than Standard Colonoscopy in Detecting Dysplasia During Long-term Surveillance of Patients With Colitis.

BACKGROUND & AIMS Patients with colitis have an increased risk of colorectal cancer, compared with persons without colitis. Many studies have shown chromoendoscopy (CE) to be superior to standard methods of detecting dysplasia in patients with colitis at index examination. We performed a prospective, longitudinal study to compare standard colonoscopy vs CE in detecting dysplasia in patients with inflammatory bowel diseases in a surveillance program. METHODS We analyzed data from 68 patients (44 men, 24 women) diagnosed with ulcerative colitis (n = 55) or Crohns disease (n = 13) at Mount Sinai Medical Center from September 2005 through October 2011. The patients were followed from June 2006 through October 2011 (median, 27.8 months); each patient was analyzed by random biopsy, targeted white light examination (WLE), and CE. Specimens were reviewed by a single blinded pathologist. The 3 methods were compared by using the generalized estimating equations method, and the odds ratios (ORs) for detection of dysplasia were calculated (primary outcome). Time to colectomy was analyzed by using the Cox model. RESULTS In the 208 examinations conducted, 44 dysplastic lesions were identified in 24 patients; 6 were detected by random biopsy, 11 by WLE, and 27 by CE. Ten patients were referred for colectomy, and no carcinomas were found. At any time during the study period, CE (OR, 5.4; 95% confidence interval [CI], 2.9-9.9) and targeted WLE (OR, 2.3; 95% CI, 1.0-5.3) were more likely than random biopsy analysis to detect dysplasia. CE was superior to WLE (OR, 2.4; 95% CI, 1.4-4.0). Patients identified as positive for dysplasia were more likely to need colectomy (hazard ratio, 12.1; 95% CI, 3.2-46.2). CONCLUSIONS In a prospective study of 68 patients with inflammatory bowel diseases, CE was superior to random biopsy or WLE analyses in detecting dysplasia in patients with colitis during an almost 28-month period. A negative result from CE examination was the best indicator of a dysplasia-free outcome, whereas a positive result was associated with earlier referral for colectomy.

The SCENIC Consensus Statement on Surveillance and Management of Dysplasia in Inflammatory Bowel Disease: Praise and Words of Caution

early a century after RosenNberg and Crohn recognized the occurrence of colorectal cancer (CRC) in ulcerative colitis, our understanding of how best to prevent this lethal complication of inflammatory bowel disease (IBD) continues to confound practitioners and disconcert patients. A profusion of recommendations about the best means to perform surveillance for dysplasia, and how best tomanage it once found, has led to considerable discord and confusion. Published simultaneously in this month’s issues of Gastroenterology and Gastrointestinal Endoscopy, the SCENIC consensus statement (Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations) hopes to bring some order to this chaotic scene. SCENIC covers a range of topics in screening and surveillance for dysplasia in colitis and addresses, head on, several areas of contention with a deliberate thoroughness and an excellent summary of the available data. Central to the statements contained in SCENIC is the placement of chromoendoscopy (CE) as the preferred technique for surveillance for dysplasia in IBD. SCENIC provides a comprehensive summary of the available data underlying this core recommendation, and may have an important impact on the field. However, it is our belief that many practical issues and the lack of longitudinal data on CE as

Surveillance in Inflammatory Bowel Disease Chromoendoscopy and Digital Mucosal Enhancement

Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer. Performing periodic dysplasia screening and surveillance may diminish this risk. To date, chromoendoscopy is the only technique that has consistently yielded positive results in large, well-designed dysplasia-detection trials. Most major society guidelines endorse chromoendoscopy as an adjunct, accepted, or preferred dysplasia-detection tool. This review outlines the available endoscopic technologies for the detection of dysplasia in IBD, considers the evidence supporting their use, and assesses which modalities are ready for use in clinical practice.

6‐mercaptopurine is effective in Crohn's disease without concomitant steroids

Background6-Mercaptopurine (6-MP) has shown efficacy in the treatment of Crohn’s disease when used in conjunction with corticosteroids. Sparse literature to date suggests that 6-MP is effective when used without steroids. We therefore studied the efficacy of 6-MP in corticosteroid-naive Crohn’s patients. MethodsWe conducted a retrospective chart review of 24 patients who were treated with 6-MP but had never received any form of steroid treatment at any time. 6-MP efficacy was assessed with serial modified Harvey-Bradshaw scores. In addition to overall response, data were also analyzed according to the indication for treating with 6-MP (disease activity, fistulae, or both). The time to relapse and the treatments required were also analyzed. ResultsOverall, remission or significant improvement was seen in 20 patients (83% of original group). Seven patients (29%) achieved complete remission; another 13 patients (54%) demonstrated significant clinical improvement. By indication, 89% of patients treated for activity, 50% of patients treated for activity and fistula, and 100% of patients treated for fistula alone showed response. Drug effect required a median of 5.7 months to occur (for all patients: range, 1.7–37.9 months). Thirteen of the twenty patients who improved or remitted on 6-MP eventually relapsed, usually due to stopping 6-MP, at a median of 13.8 months (range, 0.9–57.8). Relapse was less frequent if patients continued 6-MP. Treatment of relapses required only antibiotics, and/or restarting 6-MP (or increasing the dose) in most patients. Conclusions6-MP is an effective medication for use in steroid-naive patients and is likely to be effective in patients who have received steroids in the past but are not currently receiving them. Relapses occur despite continued therapy, but are often easily treated, and do not require initiating steroids.

The effect of intravenous cyclosporine on rates of colonic surgery in hospitalized patients with severe Crohn's colitis.

Background: The role of intravenous (IV) cyclosporine in severe Crohn’s colitis (CC) is poorly studied. Aim: Our primary aim was to determine the in-hospital colonic resection rate in patients with severe CC who received IV cyclosporine, and the potential predictors of resection among these patients. Methods: An inpatient pharmacy query of all patients who received IV cyclosporine at Mount Sinai Medical Center for 12.5 years after January 1, 1996 was reviewed. Patients with CC or indeterminate colitis favoring Crohn’s were included and their medical records were reviewed. Subsequent need for colonic surgery was assessed. A Kaplan-Meier plot with log-rank testing was performed to determine the rate of colonic surgery avoidance. Forward stepwise logistic regression was performed to determine independent predictors of surgery. Results: Forty-eight patients met our inclusion criteria. Prior thiopurine and anti-tumor necrosis factor (anti-TNF) use was 85% and 69%, respectively. The median follow-up time was 12 months (range, 1 to 60 mo). 12.5% of patients required colonic resection during their admission for IV cyclosporine. Anti-TNF use in the 4 weeks preceding IV cyclosporine was the only predictor of surgery in this setting (P=0.05). The cumulative colonic surgery avoidance rate was 72±13% at 6 months and 59±15% at 12 months. Conclusions: The use of IV cyclosporine resulted in a low rate of in-hospitalization colonic surgery among CC patients with severe disease, the majority of whom previously failed anti-TNFs and thiopurines.

Gut microbiota density influences host physiology and is shaped by host and microbial factors

To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn’s disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics.

Improving Endoscopic Detection of Dysplasia in Inflammatory Bowel Disease: Where Do We Stand?

Patients with inflammatory bowel disease (IBD) involving the colon are at increased risk of developing colorectal cancer. Surveillance colonoscopy to detect dysplasia and early colorectal cancer is therefore one of the key elements of health care maintenance in IBD patients. In general, patients with left-sided or extensive colitis should have surveillance exams every 1–2 years starting 8 years after diagnosis. Dysplasia surveillance has typically involved taking four-quadrant random biopsies throughout the colon. However, numerous studies have demonstrated that targeted examination using chromoendoscopy (CE) increases the detection of dysplastic lesions compared to standard-definition white-light colonoscopy and is recommended by the SCENIC international consensus statement. CE is an enhanced visualization technique that involves spraying the colon with a contrast dye, typically methylene blue or indigo carmine. It remains to be definitively determined if CE is better than high-definition white-light colonoscopy and if removing lesions detected by CE leads to meaningful changes in long-term management and colorectal cancer risk.