Ulcerative Colitis: Kornbluth A

Kornbluth A, Sachar DB, Anonymous00314. · The Henry D. Janowitz Division of Gastroenterology, The Department of Medicine, Mount Sinai School of Medicine, The Mount Sinai Medical Center, New York, NY 10128, USA. · Am J Gastroenterol. · Pubmed #15233681 No free full text.

Abstract: Guidelines for clinical practice are intended to indicate preferred approaches to medical problems as established by scientifically valid research. Double-blind placebo-controlled studies are preferable, but compassionate use reports and expert review articles are utilized in a thorough review of the literature conducted through Medline with the National Library of Medicine. When only data that will not withstand objective scrutiny are available, a recommendation is identified as a consensus of experts. Guidelines are applicable to all physicians who address the subject without regard to the specialty training or interests and are intended to indicate the preferable but not necessarily the only acceptable approach to a specific problem. Guidelines are intended to be flexible and must be distinguished from standards of care, which are inflexible and rarely violated. Given the wide range of specifics in any health-care problem, the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision. Guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees. Each has been extensively reviewed and revised by the Committee, other experts in the field, physicians who will use them, and specialists in the science of decision of analysis. The recommendations of each guideline are therefore considered valid at the time of their production based on the data available. New developments in medical research and practice pertinent to each guideline will be reviewed at a time established and indicated at the publication in order to assure continued validity.

Kornbluth A. · No affiliation provided · Gastrointest Endosc. · Pubmed #17531634 No free full text.

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Kornbluth A. · No affiliation provided · Am J Gastroenterol. · Pubmed #11774930 No free full text.

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Swaminath A, Kornbluth A. · Henry D. Janowitz Division of Gastroenterology, Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1069, New York, NY 10029, USA. · Curr Gastroenterol Rep. · Pubmed #18377805 No free full text.

Abstract: This article reviews current data to optimize the use of both older and newer drugs in inflammatory bowel disease. For patients with severe ulcerative colitis (UC), steroid dosing has been clarified, and a mega-analysis of steroid outcomes and toxicities has been reported. In regard to mesalamine, recent information has suggested benefit of a higher dose of pH-dependent release mesalamine for patients with moderate UC. Also, a once-daily formulation with Multi-Matrix System (MMX) technology (Shire Pharmaceuticals, Wayne, PA), has been approved. In regard to cyclosporine, two centers have reported an increased rate of colectomy over a long-duration follow-up of a cyclosporin A course given for UC. Additional information regarding thiopurines has been published, including the use of metabolite testing and duration of therapy for these drugs. Lastly, additional information regarding the optimal method for using anti-tumor necrosis factor therapy continues to accumulate.

Kornbluth A, Legnani P, Lewis BS. · Henry D. Janowitz Division of Gastroenterology, The Mount Sinai Medical Center, New York, New York, USA. · Inflamm Bowel Dis. · Pubmed #15290925 No free full text.

Abstract: In this paper, we critically review the rationale, technical issues, and diagnostic findings, difficulties in interpretation, complications, potential clinical uses, and practical obstacles for capsule endoscopy in patients with inflammatory bowel disease (IBD). We will review the currently limited data on its use in IBD and discuss future areas of investigation required to evaluate critically its potential utility in these patients.

Kane S, Lu F, Kornbluth A, Awais D, Higgins PD. · Mayo Clinic, Rochester, Minnesota, USA. · Inflamm Bowel Dis. · Pubmed #19213060 No free full text.

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Maser EA, Deconda D, Lichtiger S, Ullman T, Present DH, Kornbluth A. · The IBD Center, Division of Gastroenterology, Mount Sinai Medical Center, New York, New York 10029, USA. · Clin Gastroenterol Hepatol. · Pubmed #18928936 No free full text.

Abstract: BACKGROUND & AIMS: In patients with severe corticosteroid-refractory ulcerative colitis, cyclosporine or infliximab may be added in an effort to induce remission. If the patient then fails either of these drugs, it is unknown whether success can be achieved by using the other agent. The aim of this study was to assess outcomes of using cyclosporine after failure of infliximab, and vice versa. METHODS: We retrospectively reviewed the charts of 19 patients with corticosteroid-refractory ulcerative colitis who received either infliximab after failed cyclosporine or cyclosporine after failed infliximab. Acute salvage therapy was defined as having received the alternate drug within 4 weeks of discontinuing the first agent. RESULTS: Ten patients received infliximab after failing cyclosporine; 9 patients received cyclosporine after failing infliximab. Four patients (40%) in the infliximab-salvage group achieved remission, as did 3 (33%) in the cyclosporine-salvage group. Remission lasted a mean of 10.4 months (range, 4.4-17.03 mo) and 28.5 months (range, 5.0-41.5 mo), respectively. Severe adverse events included one patient who developed sepsis and died after receiving infliximab salvage. One patient who received cyclosporine salvage developed herpetic esophagitis, and another patient who received cyclosporine salvage developed pancreatitis and bacteremia. CONCLUSIONS: In patients with severe corticosteroid-refractory ulcerative colitis who fail treatment with either cyclosporine or infliximab, remission rates using acute salvage therapy by crossing over to the other drug occur in approximately one third of patients and have limited duration. Serious adverse events occurred in 16%, including 1 death, suggesting that the risks of acute salvage therapy may outweigh the benefits.

Ullman T, Croog V, Harpaz N, Hossain S, Kornbluth A, Bodian C, Itzkowitz S. · Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA. · Clin Gastroenterol Hepatol. · Pubmed #18848502 No free full text.

Abstract: BACKGROUND & AIMS: Some studies have suggested that mesalamine can prevent the development of colorectal cancer in patients with ulcerative colitis (UC). The aim of this study was to compare rates of progression with advanced neoplasia in patient cohorts with UC taking low and high doses of mesalamine and to determine where in the process of neoplastic progression mesalamine might act. METHODS: Three cohorts of UC patients were identified from an institutional database: 311 patients with no dysplasia (NoD), 56 with indefinite dysplasia (IND), and 26 with flat low-grade dysplasia (fLGD). The impact of mesalamine exposure on the subsequent development of advanced neoplasia (high-grade dysplasia or colorectal cancer) was assessed using life-table methods. RESULTS: Seventeen of 311 patients with NoD progressed to advanced neoplasia (5-year rate, 1.1%). This rate was lower than the 5-year rate for the IND (9%; P = .02 vs NoD) and fLGD (45%; P < .001 vs NoD and P = .001 vs IND) cohorts. Among the NoD cohort, the hazard ratio for mesalamine users versus nonusers was 0.70 (95% confidence interval, 0.20-2.44), and for each 1 g/d increase in dose, the hazard ratio was 0.92 (95% confidence interval, 0.58-1.47). For patients with IND, no patients on greater than 2 g/d progressed versus 13.8% on low-dose mesalamine (P = .11). For fLGD, 62.5% on high dose progressed, versus 27.8% on low dose (P = .054). CONCLUSIONS: In long-standing UC, patients with fLGD have a higher rate of progression to advanced neoplasia than those with NoD or IND. However, at none of these stages of disease did mesalamine use show definitive chemopreventive activity.

Gupta RB, Harpaz N, Itzkowitz S, Hossain S, Matula S, Kornbluth A, Bodian C, Ullman T. · Department of Medicine, The University of Texas Southwestern, Dallas, Texas, USA. · Gastroenterology. · Pubmed #17919486 links to  free full text

Abstract: BACKGROUND & AIMS: Although inflammation is presumed to contribute to colonic neoplasia in ulcerative colitis (UC), few studies have directly examined this relationship. Our aim was to determine whether severity of microscopic inflammation over time is an independent risk factor for neoplastic progression in UC. METHODS: A cohort of patients with UC undergoing regular endoscopic surveillance for dysplasia was studied. Degree of inflammation at each biopsy site had been graded as part of routine clinical care using a highly reproducible histologic activity index. Progression to neoplasia was analyzed in proportional hazards models with inflammation summarized in 3 different ways and each included as a time-changing covariate: (1) mean inflammatory score (IS-mean), (2) binary inflammatory score (IS-bin), and (3) maximum inflammatory score (IS-max). Potential confounders were analyzed in univariate testing and, when significant, in a multivariable model. RESULTS: Of 418 patients who met inclusion criteria, 15 progressed to advanced neoplasia (high-grade dysplasia or colorectal cancer), and 65 progressed to any neoplasia (low-grade dysplasia, high-grade dysplasia, or colorectal cancer). Univariate analysis demonstrated significant relationships between histologic inflammation over time and progression to advanced neoplasia (hazard ration (HR), 3.0; 95% CI: 1.4-6.3 for IS-mean; HR, 3.4; 95% CI: 1.1-10.4 for IS-bin; and HR, 2.2; 95% CI: 1.2-4.2 for IS-max). This association was maintained in multivariable proportional hazards analysis. CONCLUSIONS: The severity of microscopic inflammation over time is an independent risk factor for developing advanced colorectal neoplasia among patients with long-standing UC.

Nilubol N, Scherl E, Bub DS, Gorfine SR, Marion J, Harris MT, Kornbluth A, Lichtiger S, Rubin P, George J, Chapman M, Harpaz N, Present D, Bauer JJ. · Department of Surgery, The Mount Sinai Hospital, New York, New York, USA. · Dis Colon Rectum. · Pubmed #17429711 No free full text.

Abstract: PURPOSE: Inflammation, villous atrophy, colonic metaplasia, and dysplasia have been observed within the mucosa of ileal pelvic pouches after restorative proctocolectomy. This study was designed to determine the prevalence of mucosal dysplasia in ileal pouch and any associated risk factors. METHODS: Prospectively registered patients having restorative proctocolectomy were recruited. A cross-sectional study was performed using a questionnaire focusing on disease history, functional results, and pouchitis after surgery. Participants underwent screening endoscopic pouch examination using sigmoidoscopy. Mucosal biopsies were taken from six specific locations in the pouch from proximal ileal-pouch (inflow) to ileoanal anastomosis. All biopsies were performed under strict surveillance protocol regardless of patients' symptoms. Biopsies were interpreted by two pathologists unaware of each other's report. RESULTS: A total of 138 patients completed the protocol. Colectomy specimens from restorative proctocolectomy showed chronic ulcerative colitis in 118 (85.6 percent), familial adenomatous polyposis in 10 (7.2 percent), Crohn's colitis in 2 (1.4 percent), and indeterminate colitis in 8 (5.8 percent) patients. Twenty-two patients (18.3 percent) had dysplasia and eight (6.7 percent) had invasive cancer found in colectomy specimens after restorative proctocolectomy. Median interval between proctocolectomy and pouch biopsy was 5.4 years. Inflammatory changes were present in a majority of specimens, but these did not correlate with clinical history of pouchitis. No villous atrophy was identified. Pouch biopsies from only one patient were indefinite for dysplasia. Subsequent biopsies were negative. CONCLUSIONS: Clinical and microscopic evidence of ileal-pouch inflammation is common. Ileal-pouch mucosal dysplasia is uncommon, occurring in only 1 of 138 patients. Villous atrophy and colonic metaplasia were not observed in this series. Routine pouch surveillance with biopsies may not be warranted.

Kornbluth A, Hayes M, Feldman S, Hunt M, Fried-Boxt E, Lichtiger S, Legnani P, George J, Young J. · The Henry D. Janowitz Division of Gastroenterology, The Mount Sinai Medical Center, New York, New York, USA. · Am J Gastroenterol. · Pubmed #16863559 No free full text.

Abstract: OBJECTIVE: The American College of Gastroenterology (ACG) and American Gastroenterology Association (AGA) have both recently issued guidelines (the "Guidelines") regarding the diagnosis and management of osteoporosis in patients with inflammatory bowel disease (IBD). The objective of this study was to determine the yield of implementing the Guidelines' recommendations in a prospective cohort of IBD patients and identify the prevalence of bone loss, risk factors, and potential influence on management. METHODS: One hundred consecutive IBD patients who fulfilled the Guidelines' criteria underwent dual energy X-ray absorptiometry scanning (DEXA) scanning of the lumbar vertebrae and bilateral hips. Demographic data, risk factor information, and changes in therapy based on screening were collected and analyzed. RESULTS: Indications for screening were history of prolonged past or concurrent steroid use (92%), postmenopausal status (7%), and history of low trauma fracture (7%). Forty-four percent of patients had osteopenia of either the lumbar spine or the hips, 12% had osteoporosis of either the spine or hips, and 44% had normal bone density. In a univariate analysis, factors predicting a greater likelihood of osteoporosis (but not osteopenia) were a diagnosis of Crohn's disease (vs. ulcerative colitis), low body mass index in women, and postmenopausal status. Specific therapies based on DEXA findings were initiated in 69% of patients: oral calcium and vitamin D supplementation in 69% and an oral bisphoshphonate in 20%. CONCLUSIONS: Implementation of the Guidelines led to the detection of osteopenia or osteoporosis and initiation of specific therapies in a majority of patients who met the Guidelines' criteria for DEXA screening.

Hanauer SB, Sandborn WJ, Kornbluth A, Katz S, Safdi M, Woogen S, Regalli G, Yeh C, Smith-Hall N, Ajayi F. · Division of Gastroenterology, University of Chicago Medical Center, Chicago, Illinois 60637, USA. · Am J Gastroenterol. · Pubmed #16279903 No free full text.

Abstract: BACKGROUND AND AIMS: Preliminary data have shown that delayed release oral mesalamine (Asacol) dosed at 4.8 g/day provided additional efficacy benefit compared to 1.6 g/day in patients with mildly to moderately active ulcerative colitis. Additionally, Asacol dosed at 2.4 g/day has been proved to be more effective than 1.6 g/day. Whether 4.8 g/day of mesalamine (dosed with an investigational 800 mg tablet) is more effective than Asacol 2.4 g/day (dosed with a 400 mg tablet) in patients with moderately active ulcerative colitis is unknown. METHODS: A randomized, double-blind, controlled trial (ASCEND II) was conducted to evaluate the efficacy of 4.8 g/day of mesalamine in adults with active ulcerative colitis. Three hundred eighty-six patients with mild to moderate ulcerative colitis were randomized for treatment with mesalamine 2.4 g/day (400 mg tablet) or 4.8 g/day (800 mg tablet) for 6 wk. The primary efficacy population was 268 patients with moderately active ulcerative colitis treated with 2.4 g/day (n = 139) or 4.8 g/day (n = 129). The primary endpoint was the proportion of patients in each treatment group that achieved overall improvement ("treatment success," defined as either complete remission or a clinical response to therapy) from baseline at week 6. RESULTS: Seventy-two percent of patients receiving 4.8 g/day of mesalamine for moderate ulcerative colitis (89/124 patients) achieved treatment success at week 6, compared with 59% of those who received 2.4 g/day (77/130 patients) (p= 0.036). Both regimens were well tolerated. Adverse events and clinically significant changes in laboratory results were similar in both treatment groups. CONCLUSIONS: Patients with moderately active ulcerative colitis treated with 4.8 g/day of mesalamine (800 mg tablet) are significantly more likely to achieve overall improvement at 6 wk compared to patients treated with 2.4 g/day.

Su C, Salzberg BA, Lewis JD, Deren JJ, Kornbluth A, Katzka DA, Stein RB, Adler DR, Lichtenstein GR. · Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA. · Am J Gastroenterol. · Pubmed #12385442 No free full text.

Abstract: OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) is an important cytokine involved in the pathogenesis of inflammatory bowel disease. The monoclonal antibody to TNF-alpha, infliximab, is effective in treating Crohn's disease. Preclinical studies suggest the importance of TNF-alpha in treating ulcerative colitis (UC). We report the effectiveness of infliximab for UC and examine factors predictive of response to medication. METHODS: Data from all UC patients receiving infliximab at four institutions were analyzed. Disease activity was determined by the Disease Activity Index. RESULTS: A total of 27 patients with active UC received inpatient (37%) and outpatient (63%) infliximab as single (52%) or multiple (two to 15) infusions (48%). Twelve patients (44%) achieved remission and six patients (22%) had partial response. Nine patients had no response; five subsequently underwent total colectomy. The median time to achieve response and remission was 4 days and the median duration 8 wk. Nine of the 18 patients who responded experienced 19 relapses; 18 of these relapses (95%) were successfully treated with repeat infusions. Steroid-refractory patients were less likely to respond to infliximab therapy than were steroid-responsive patients (33% vs 83%; p = 0.026). No other factors were predictive of response to infliximab. Two patients developed serious adverse events, including death in one case. CONCLUSIONS: Preliminary evidence suggest effectiveness of infliximab in the treatment of UC, including medically refractory severe disease. Individuals who are refractory to corticosteroids, however, may be unlikely to respond to infliximab. A randomized controlled trial is necessary to further investigate the efficacy of infliximab in patients with UC.

Legnani PE, Kornbluth A. · The Henry D. Janowitz Division of Gastroenterology, The Mount Sinai Medical Center, New York, NY, USA. · Semin Gastrointest Dis. · Pubmed #11726075 No free full text.

Abstract: When considered in the appropriate clinical scenarios, the diagnoses of Crohn's disease or ulcerative colitis are usually straightforward. Most cases can be definitively diagnosed by the typical subacute or chronic history of symptoms, and radiographic, endoscopic, and histologic confirmation in the presence of negative stool studies; newer serologic assays are now available and are of value if the diagnosis remains uncertain. In this paper, we review distinguishing features in the diagnosis of ileitis and the distinction to be made in conclusively diagnosing ulcerative vs. Crohn's colitis.