Ulcerative Colitis: Loftus EV

Loftus EV. · No affiliation provided · Clin Gastroenterol Hepatol. · Pubmed #15017627 No free full text.

This publication has no abstract.

Jones JL, Loftus EV. · Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada. · Inflamm Bowel Dis. · Pubmed #17600819 links to  free full text

Abstract: With the increasingly widespread use of immunosuppressive and biologic agents for the treatment of Crohn's disease and ulcerative colitis come concerns about potential long-term consequences of such therapies. Disentangling the potential confounding effects of the underlying disease, its extent, severity, duration, and behavior, and concomitant medical therapy has proven to be exceedingly difficult. Unlike the case in rheumatoid arthritis, the overwhelming preponderance of population-based evidence suggests that a diagnosis of inflammatory bowel disease (IBD) is not associated with an increased relative risk of lymphoma. However, well-designed studies that evaluate the potential modifying effect of IBD severity have yet to be performed. Although the results from hospital- and population-based studies have conflicted, the results of a recent meta-analysis suggest that patients receiving purine analogs for the treatment of IBD have a lymphoma risk approximately 4-fold higher than expected. Analyses of lymphoma risk in patients receiving biologic agents directed against tumor necrosis factor-alpha are confounded by concomitant use of immunosuppressive agents in most of these patients. Nevertheless, there may be a small but real risk of lymphoma associated with these therapies. Although the relative risk of lymphoma may be elevated in association with some of the medical therapies used in the treatment of IBD, this absolute risk is low. Weighing the potential risk of lymphoma associated with select medical therapies against the risk of undertreating IBD will help physicians and patients to make more informed decisions pertaining to the medical management of IBD.

Loftus EV. · Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. · Gastroenterol Clin North Am. · Pubmed #16952738 No free full text.

Abstract: Patients with UC are at increased risk of CRC, but a series of population-based studies published within the past 5 years suggest that this risk has decreased over time. The crude annual incidence rate of CRC in UC ranges from approximately 1 in 500 to 1 in 1600. In some cohorts, an elevated risk of CRC relative to the general population can no longer be demonstrated. The exact mechanism for this decrease in risk remains unclear but may be attributable to a combination of more widespread use of maintenance therapy and surveillance colonoscopy as well as more judicious reliance on colectomy. In addition to the classic risk factors of increased extent and duration of UC, it seems that PSC, a family history of sporadic CRC, severity of histologic bowel inflammation, and young age at colitis onset are independent risk factors for cancer.

Leighton JA, Loftus EV. · Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, 13400 E. Shea Boulevard, Scottsdale, AZ 85259, USA. · Curr Gastroenterol Rep. · Pubmed #16313877 No free full text.

Abstract: Over the past several years, significant advances have been made in the diagnostic techniques used in the management of ulcerative colitis and Crohn's disease. These advances have occurred mainly in the area of gastrointestinal endoscopy and radiology. Capsule endoscopy and double-balloon endoscopy have permitted better visualization of the small bowel mucosa. Advanced imaging techniques, including chromoendoscopy, magnification endoscopy, confocal endomicroscopy, and spectroscopy, may aid in the diagnosis of colorectal neoplasia in patients with long-standing disease. Improved radiographic imaging techniques based on computed tomography and magnetic resonance imaging allow noninvasive means of evaluating the small bowel in patients with known or suspected Crohn's disease. Finally, positron emission tomography is an investigative tool for inflammatory bowel disease that may also aid in the detection of inflammation in these diseases.

Loftus EV. · Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN 55905, USA. · Curr Gastroenterol Rep. · Pubmed #15527681 No free full text.

Abstract: The past 18 months have seen many studies of the prevalence, pathogenesis, and treatment of the extraintestinal manifestations of inflammatory bowel disease (IBD). Inhibitors of tumor necrosis factor alpha have shown effectiveness in randomized trials for the treatment of spondyloarthropathies and ocular manifestations. Open-label studies suggest that these agents may be effective for pyoderma gangrenosum as well. The epidemiology of primary sclerosing cholangitis (PSC), and its relationship to IBD, is becoming clearer. Colorectal neoplasia in PSC remains an important clinical problem. Osteoporosis occurs more commonly in IBD, but the relative importance of corticosteroid use versus underlying chronic bowel inflammation as risk factors remains controversial. Chromoendoscopy may be an important means to improve detection of colorectal neoplasia in IBD. Observational studies suggest that prolonged use of aminosalicylates is associated with decreased risk of neoplasia, but data are conflicting. A randomized trial of ursodeoxycholic acid in PSC showed decreased risk of colorectal neoplasia in patients receiving the drug relative to those on placebo.

Loftus EV, Kane SV, Bjorkman D. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA. · Aliment Pharmacol Ther. · Pubmed #14723609 links to  free full text

Abstract: AIM: To determine whether there is a difference in short-term adverse events in patients with ulcerative colitis treated with mesalazine, olsalazine or balsalazide. METHODS: MEDLINE was searched for articles published until 2002. Randomized trials of oral mesalazine, olsalazine or balsalazide for the treatment of active disease or the maintenance of remission were included. Outcomes of interest were the frequencies of patients experiencing adverse events and those withdrawn due to adverse events. RESULTS: Forty-six trials were included. One study of mesalazine vs. sulfasalazine for active colitis showed significantly fewer patients with adverse events with mesalazine. Both balsalazide vs. sulfasalazine studies for active disease showed significantly fewer withdrawals with balsalazide. One trial of balsalazide vs. sulfasalazine for maintenance showed significantly fewer patients with adverse events with balsalazide. Otherwise, no significant differences in safety outcomes were noted. CONCLUSION: All three 5-aminosalicylic acid agents are safe in the short term. In mesalazine-treated patients, the frequencies of adverse events or withdrawals due to adverse events were comparable with those in placebo-treated patients and lower than those in sulfasalazine-treated patients. Overall, adverse events or withdrawals were not significantly more frequent with olsalazine than with placebo or sulfasalazine. Adverse events and study withdrawals on balsalazide were less frequent than those on sulfasalazine.

Pardi DS, Loftus EV, Camilleri M. · Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA. · Drugs Aging. · Pubmed #12093322 No free full text.

Abstract: Inflammatory bowel disease (IBD) is most common in young adults, but it can also present in the elderly. Furthermore, with the aging of the population, the number of elderly patients with IBD is expected to grow. Other conditions, such as diverticulitis and ischaemic colitis, may be more common in the elderly and need to be considered in the differential diagnosis. Management of elderly patients with IBD follows the same principles as in younger patients, with a few exceptions. For patients with mild-to-moderate colitis, a 5-aminosalicylate drug is often used (sulfasalazine, olsalazine, mesalazine, balsalazide). Topical therapy may be sufficient for those with distal colitis, whereas an oral preparation is used for more extensive disease. In those with more severe or refractory symptoms, corticosteroids are used, although the elderly appear to be at increased risk for corticosteroid-associated complications. For patients with corticosteroid-dependent or corticosteroid-refractory disease, immunosuppression with azathioprine or mercaptopurine may help avoid surgery. In patients with Crohn's disease, a similar approach is followed, with the additional consideration that the formulation of drug used must ensure delivery of drug to the site of inflammation. In fistulising Crohn's disease, antibacterials, immunosuppressive drugs, infliximab and surgery are often used in combination. Controlled trials and clinical experience have shown that infliximab is a significant addition to the therapeutic armamentarium for patients with Crohn's disease.

Yang SK, Loftus EV, Sandborn WJ. · Department of Internal Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea. · Inflamm Bowel Dis. · Pubmed #11515854 No free full text.

Abstract: Studies of Asians in Asia show relatively low incidence rates for ulcerative colitis and Crohn's disease compared with North America and Europe. The prevalence of ulcerative colitis in migrant South Asians in Europe is similar to Europeans, whereas the prevalence of Crohn's disease for migrant South Asians in Europe is decreased compared with Europeans. The prevalence for both ulcerative colitis and Crohn's disease in Japan and Korea is relatively low. There are no obvious differences in age or sex distribution or rates of familial aggregation, and there are no significant differences in the clinical characteristics and natural history of ulcerative colitis and Crohn's disease in Asians compared with other racial groups with inflammatory bowel disease.

Sandborn WJ, Sands BE, Wolf DC, Valentine JF, Safdi M, Katz S, Isaacs KL, Wruble LD, Katz J, Present DH, Loftus EV, Graeme-Cook F, Odenheimer DJ, Hanauer SB. · Mayo Clinic, Rochester, MN, USA. · Aliment Pharmacol Ther. · Pubmed #12786629 links to  free full text

Abstract: BACKGROUND: Repifermin (keratinocyte growth factor-2) has been shown to reduce inflammation in animal models of colitis. AIM: To evaluate repifermin for the treatment of active ulcerative colitis. METHODS: Eighty-eight patients with active ulcerative colitis were enrolled in a 6-week, double-blind trial. Patients were randomized to receive treatment for five consecutive days with intravenous repifermin at a dose of 1, 5, 10, 25 or 50 microg/kg, or placebo. The primary objective of the study was to evaluate the safety of repifermin. The primary efficacy outcome was clinical remission at week 4, defined as a score of zero on the endoscopic appearance and stool blood components of the Mayo score and a score of zero or unity on the stool frequency and physician's global assessment components. RESULTS: At week 4, the rates of clinical remission in the 1, 5, 10, 25 and 50 microg/kg repifermin groups were 19%, 9%, 0%, 0% and 0%, respectively, and 11% for the placebo group (P = 0.32 for repifermin vs. placebo). The frequencies of commonly occurring adverse events and severe adverse events were similar in both groups. CONCLUSIONS: Intravenous repifermin at a dose of 1-50 microg/kg was very well tolerated, but there was no evidence that repifermin was effective for the treatment of active ulcerative colitis at these doses. An additional study to determine the efficacy of repifermin at doses of > 50 microg/kg or for a longer treatment duration may be warranted, as the maximally tolerated dose was not reached in the present study.

Pardi DS, Loftus EV, Kremers WK, Keach J, Lindor KD. · Division of Gastroenterology and Hepatology and Division of Biostatistics, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. · Gastroenterology. · Pubmed #12671884 No free full text.

Abstract: BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) has shown effectiveness as a colon cancer chemopreventive agent in preclinical studies. In addition, a recent report suggests that it also may decrease the risk for developing colorectal dysplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We sought to evaluate the effect of UDCA on colorectal neoplasia in a group of patients with UC and PSC enrolled in a randomized, placebo-controlled trial. METHODS: From a prior, randomized, placebo-controlled trial of UDCA therapy in PSC at our center, we followed-up patients with concomitant UC to assess the effect of UDCA on the development of colorectal dysplasia and cancer as compared with placebo. ReESULTS: Fifty-two subjects were followed-up for a total of 355 person-years. Those originally assigned to receive UDCA had a relative risk of 0.26 for developing colorectal dysplasia or cancer (95% confidence interval, 0.06-0.92; P = 0.034). Many of the patients originally assigned to the placebo group eventually received open-label UDCA. Assigning these patients to the UDCA group from the time they began active therapy did not change the magnitude of the protective effect (relative risk, 0.26; 95% confidence interval, 0.07-0.99; P = 0.049). CONCLUSIONS: UDCA significantly decreases the risk for developing colorectal dysplasia or cancer in patients with UC and PSC.

Pardi DS, Loftus EV, Tremaine WJ, Sandborn WJ, Alexander GL, Balm RK, Gostout CJ. · Inflammatory Bowel Disease Clinic and GI Bleeding Team, Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, Minnesota, USA. · Gastrointest Endosc. · Pubmed #9925691 No free full text.

Abstract: BACKGROUND: Acute major gastrointestinal hemorrhage is uncommon in inflammatory bowel disease. METHODS: We characterized the clinical features and course of such hemorrhage in patients at our institution from 1989 to 1996. RESULTS: Thirty-one patients had acute lower gastrointestinal bleeding from inflammatory bowel disease and one had upper gastrointestinal bleeding from duodenal Crohn's disease. Three patients had ulcerative colitis and 28 had Crohn's disease, representing 0.1% of admissions for ulcerative colitis and 1.2% for Crohn's disease. In addition, another patient bled from an ileal J-pouch. In patients with Crohn's disease, the site of bleeding was duodenal in 1, small intestinal in 9, ileocolonic in 8, and colonic in 10. All ulcerative colitis patients had pancolitis. Medical therapy was initiated in 27 patients, including endoscopic therapy in 3. Five patients underwent surgery immediately, and 7 medically treated patients eventually required surgery for ongoing or recurrent bleeding. CONCLUSIONS: Acute major gastrointestinal bleeding is uncommon in inflammatory bowel disease. Most cases are due to Crohn's disease, without a predilection for site of involvement. The presence of an endoscopically treatable lesion is uncommon, and surgery is required in less than half of cases during the initial hospitalization. Recurrent hemorrhage is not rare, and for these cases surgery may be the most appropriate treatment.

Bourreille A, Ignjatovic A, Aabakken L, Loftus EV, Eliakim R, Pennazio M, Bouhnik Y, Seidman E, Keuchel M, Albert JG, Ardizzone S, Bar-Meir S, Bisschops R, Despott EJ, Fortun PF, Heuschkel R, Kammermeier J, Leighton JA, Mantzaris GJ, Moussata D, Lo S, Paulsen V, Panés J, Radford-Smith G, Reinisch W, Rondonotti E, Sanders DS, Swoger JM, Yamamoto H, Travis S, Colombel JF, Van Gossum A, Anonymous00249. · Institut des Maladies de l'Appareil Digestif, CHU, Université de Nantes, Nantes, France. · Endoscopy. · Pubmed #19588292 No free full text.

Abstract: Crohn's disease and ulcerative colitis are lifelong diseases seen predominantly in the developed countries of the world. Whereas ulcerative colitis is a chronic inflammatory condition causing diffuse and continuous mucosal inflammation of the colon, Crohn's disease is a heterogeneous entity comprised of several different phenotypes, but can affect the entire gastrointestinal tract. A change in diagnosis from Crohn's disease to ulcerative colitis during the first year of illness occurs in about 10 % - 15 % of cases. Inflammatory bowel disease (IBD) restricted to the colon that cannot be characterized as either ulcerative colitis or Crohn's disease is termed IBD-unclassified (IBDU). The advent of capsule and both single- and double-balloon-assisted enteroscopy is revolutionizing small-bowel imaging and has major implications for diagnosis, classification, therapeutic decision making and outcomes in the management of IBD. The role of these investigations in the diagnosis and management of IBD, however, is unclear. This document sets out the current Consensus reached by a group of international experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th December 2008, organised jointly by the European Crohn's and Colitis Organisation (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED). The Consensus is grouped into seven sections: definitions and diagnosis; suspected Crohn's disease; established Crohn's disease; IBDU; ulcerative colitis (including ileal pouch-anal anastomosis [IPAA]); paediatric practice; and complications and unresolved questions. Consensus guideline statements are followed by comments on the evidence and opinion. Statements are intended to be read in context with qualifying comments and not read in isolation.

Loftus EV, Friedman HS, Delgado DJ, Sandborn WJ. · Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA. · Inflamm Bowel Dis. · Pubmed #19143006 No free full text.

Abstract: BACKGROUND: We describe colectomy subtypes, follow-up surgical and diagnostic procedures, complications, and direct medical charges occurring within 180 days of colectomy among privately insured patients with ulcerative colitis (UC). METHODS: This was a retrospective analysis of an insurance claims database for 2001-2005. We identified patients with a diagnosis of UC and no concurrent diagnosis of Crohn's disease who underwent colectomy. Colectomy types were classified as: 1) total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA), 2) subtotal colectomy (SC) with ileostomy and Hartmann pouch or ileorectal anastomosis, 3) TPC with ileostomy, and 4) partial colectomy (PC). Follow-up surgical and diagnostic procedures and complications were collected. We developed estimates for UC-related charges for hospitalizations, outpatient visits, and medications for the time period 180 days before and after colectomy. RESULTS: A total of 55,934 UC patients were identified, of whom 540 had a colectomy and at least 180 days of pre- and postcolectomy follow-up. The colectomy distribution was: TPC-IPAA, 44%; SC-ileostomy, 22%; TPC-ileostomy, 17%; and PC, 17%. Within 180 days after colectomy, 54% of patients had a second colectomy-related surgery, and 27% had a follow-up diagnostic procedure. Complications following colectomy for UC included: abscesses (11.5% early / 14.6% late), sepsis/pneumonia/bacteremia (9.3% early / 10.0% late), and fistulas (3.9% early / 8.3% late). The mean UC-related direct medical charge for the 180 days following and including initial colectomy was $90,445. CONCLUSIONS: In this retrospective study of privately insured UC patients, we observed frequent follow-up surgical/diagnostic procedures, identified several complications postcolectomy, and estimated substantial charges 6 months pre- and postcolectomy.

Rubin DT, Siegel CA, Kane SV, Binion DG, Panaccione R, Dubinsky MC, Loftus EV, Hopper J. · Section of Gastroenterology, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois, USA. · Inflamm Bowel Dis. · Pubmed #19067414 No free full text.

Abstract: BACKGROUND: Two national internet surveys were conducted to understand how patients perceive the impact of ulcerative colitis (UC) relative to gastroenterologists. METHODS: In total, 451 patients with UC (20% mild, 63% moderate, 13% severe, 4% unsure [patient self-assessment]) were recruited for one survey and 300 gastroenterologists (not associated with the patients) were recruited for the other survey. RESULTS: Patients reported, on average, 8 (self-defined) flares per year; this was more than the number anticipated by gastroenterologists. Sixty-two percent of patients with UC reported that their disease made it difficult to lead a normal life, compared with gastroenterologists' estimations of 36%. Only 42% of patients believed that being in remission could mean living without symptoms. Both patients and gastroenterologists reported that it is difficult for patients to take medication as prescribed every day (42% and 90%) and that managing UC medication is a struggle for patients (49% and 41%). Forty-six percent of patients admitted nonadherence to their therapy over the previous week, while gastroenterologists believed that 41% of their patients were not adherent. CONCLUSIONS: These surveys identified disparities between patients' and gastroenterologists' perceptions of the impact of UC on patients' lives. The results suggest that more patients than gastroenterologists estimated chose to adapt their lives to accommodate UC rather than act to optimize therapy and adherence. Improved communication between patients and gastroenterologists, as well as better management strategies and education are necessary.

Loftus EV, Delgado DJ, Friedman HS, Sandborn WJ. · Division of Gastroenterology & Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. · Am J Gastroenterol. · Pubmed #18564126 No free full text.

Abstract: PURPOSE: We sought to describe the types of colectomy, follow-up surgical/diagnostic procedures, and complications occurring within 180 days of colectomy in a population of privately insured individuals with ulcerative colitis (UC). METHODS: This was a retrospective analysis of claims data of privately insured patients (MarketScan) for the years 2001-2004. We identified a cohort of patients with UC who underwent colectomy. Colectomies were classified into four categories based on the surgery occurring on the first colectomy date: (a) total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA), (b) subtotal colectomy (SC) with ileostomy and Hartmann pouch or ileorectal anastomosis, (c) TPC with ileostomy, and (d) partial colectomy (PC). Follow-up surgical/diagnostic procedures and complications were compared across colectomy categories. RESULTS: A total of 25,586 UC patients were identified, of whom 215 patients had a colectomy and at least 180 days of pre- and postcolectomy follow-up. The colectomy distribution was: TPC-IPAA (52%), SC-ileostomy (22%), TPC-ileostomy (14%), and PC (13%). Within 180 days postcolectomy, 54% of patients had a second colectomy-related surgery (including unplanned surgeries in 15.3%), and 27% had a follow-up diagnostic procedure. Postcolectomy complications included abscesses (11.6% in the first 30 days postcolectomy, 16.3% in the day 31-180 postcolectomy period), fistulas (4.2% early, 6.0% late), and sepsis/pneumonia/bacteremia (7.9% early, 9.3% late). CONCLUSION: Postcolectomy surgical procedures and complications occur frequently after colectomy in privately insured patients with UC.

Peloquin JM, Pardi DS, Sandborn WJ, Fletcher JG, McCollough CH, Schueler BA, Kofler JA, Enders FT, Achenbach SJ, Loftus EV. · Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. · Am J Gastroenterol. · Pubmed #18564113 No free full text.

Abstract: OBJECTIVE: For diagnosis, assessing disease activity, complications and extraintestinal manifestations, and monitoring response to therapy, patients with inflammatory bowel disease undergo many radiological studies employing ionizing radiation. However, the extent of radiation exposure in these patients is unknown. METHODS: A population-based inception cohort of 215 patients with inflammatory bowel disease from Olmsted County, Minnesota, diagnosed between 1990 and 2001, was identified. The total effective dose of diagnostic ionizing radiation was estimated for each patient. Linear regression was used to assess the median total effective dose since symptom onset. RESULTS: The number of patients with Crohn's disease and ulcerative colitis was 103 and 112, with a mean age at diagnosis of 38.6 and 39.4 yr, respectively. Mean follow-up was 8.9 yr for Crohn's disease and 9.0 yr for ulcerative colitis. Median total effective dose for Crohn's disease was 26.6 millisieverts (mSv) (range, 0-279) versus 10.5 mSv (range, 0-251) for ulcerative colitis (P < 0.001). Computed tomography accounted for 51% and 40% of total effective dose, respectively. Patients with Crohn's disease had 2.46 times higher total effective dose than ulcerative colitis patients (P= 0.001), adjusting for duration of disease. CONCLUSIONS: Annualizing our data, the radiation exposure in the inflammatory bowel disease population was equivalent to the average annual background radiation dose from naturally occurring sources in the U.S. (3.0 mSv). However, a subset of patients had substantially higher doses. The development of imaging management guidelines to minimize radiation dose, dose-reduction techniques in computed tomography, and faster, more robust magnetic resonance techniques are warranted.

Garrity-Park MM, Loftus EV, Bryant SC, Sandborn WJ, Smyrk TC. · Division of Experimental Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA. · Am J Gastroenterol. · Pubmed #18289203 No free full text.

Abstract: OBJECTIVES: Ulcerative colitis (UC) is characterized by chronic recurrent mucosal inflammation. Genetic studies in UC have indicated linkage to chromosome 6 in the region of the tumor necrosis factor-alpha (TNF-alpha) gene, a potent proinflammatory cytokine. TNF-alpha production is influenced by multiple factors including the type of immune cell and its level of activation. However, several single nucleotide polymorphisms (SNP) in the promoter region of TNF-alpha have been correlated with either increased or decreased production, indicating that regulation of TNF-alpha is in part genetic. Because UC patients are at increased risk for developing colorectal cancer (CRC), we investigated if there was an association between SNPs in the promoter of the TNF-alpha gene and UC-CRC. METHODS: DNA was extracted from formalin-fixed, paraffin-embedded tissue from 114 UC-CRC cases and 114 UC-no CRC controls. Controls were frequency matched on duration and extent of colitis, age, ethnicity, and gender. All 228 tissue samples were analyzed for five TNF-alpha promoter polymorphisms (-238[G-->A], -308[G-->A], -857[C-->T], -863[C-->A], and -1031[T-->C]) using PCR and sequencing. RESULTS: The -308(G-->A) SNP was significantly associated with UC-CRC cases at both the allele and genotype level (P < 0.0001). No other SNPs were significantly associated with UC-CRC. CONCLUSION: We report a novel finding of a strong association between the -308(G-->A) SNP and UC-CRC. Complete elucidation of the mechanism of UC-CRC carcinogenesis will require investigation of other genes involved in modulating inflammation, but our results suggest that some UC patients may have additional genetic predispositions toward developing UC-CRC.

Cima RR, Anderson KJ, Larson DW, Dozois EJ, Hassan I, Sandborn WJ, Loftus EV, Pemberton JH. · Division of Colon and Rectal Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. · Inflamm Bowel Dis. · Pubmed #17567877 links to  free full text

Abstract: BACKGROUND: Patient education is known to improve satisfaction in and participation with treatment. A careful assessment of internet use by inflammatory bowel disease (IBD) patients to gather information has not been reported. Our aim was to evaluate internet use to gather general health- and disease-specific information in patients presenting to an IBD clinic. METHODS: A cross-sectional anonymous survey using a convenience sample of patients (N = 175) at a tertiary-care institution's IBD clinic was performed. RESULTS: In all, 169 surveys (97%) were returned for analysis. The median age was 46 (17-84), 83 men and 81 women (5 missing). In known IBD patients (87%), 85 (50%) had Crohn's disease and 62 (37%) ulcerative colitis; 81% of patients had home internet access. The most common information sources were: gastroenterologists (59%), internet (54%), and primary-care physicians (54%). Ninety-two patients (54%) used the internet to gather IBD-specific information. Age-specific use (<40, 40-65, >65) was 73%, 48%, 37.5%, respectively. There was a significant positive association between level of education and internet use (P < 0.0001), but not with income. Internet sites most commonly visited were organization- or institution-specific. Factors that most influenced a user's choice of an internet site were noncommercial status (59%) and ease of use (53%). The majority of patients (57%) rated internet information "trustworthy" to "very trustworthy." CONCLUSIONS: Over half of patients in an IBD clinic used the internet to gather IBD-specific information. Use was inversely associated with age and positively correlated with education level. There was no income association. These findings suggest web-based IBD information may become increasingly important in the future.

Tremaine WJ, Timmons LJ, Loftus EV, Pardi DS, Sandborn WJ, Harmsen WS, Thapa P, Zinsmeister AR. · Division of Gastroenterology and Hepatology, Fiterman Center, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. · Aliment Pharmacol Ther. · Pubmed #17539983 No free full text.

Abstract: BACKGROUND: There is conflicting data regarding the response to medical and surgical therapy for inflammatory bowel disease with respect to age at disease onset. AIM: To determine if the age at onset of Crohn's disease and ulcerative colitis is a risk factor for surgery for non-neoplastic bowel disease. METHODS: This was a case-control study of patients evaluated between 1998 and 2001. Cases had undergone an initial operation for bowel disease. Controls were matched 1:1 for gender, disease subtype, date of first visit (+/-2 years), time from diagnosis prior to first visit (+/-3 years) and duration of follow-up. Association with age, disease extent, smoking history, medication use and co-morbidities vs. case/control status was assessed using multiple variable conditional logistic regression to estimate the odds ratio (OR) and 95% confidence intervals (CI) for undergoing surgery. RESULTS: Among 132 Crohn's patients, older patients had lower odds for surgery (OR per 5 years, 0.86; 95% CI: 0.75-0.98). The rate of surgery for non-neoplastic bowel disease was not significantly associated with disease distribution, co-morbidities or cigarette smoking. Among 234 ulcerative colitis patients, the rate of surgery was unrelated to age, disease extent, co-morbidities or cigarette smoking, CONCLUSIONS: For Crohn's disease, but not ulcerative colitis, the risk of surgery for non-neoplastic bowel disease decreases with increasing age at diagnosis, irrespective of disease distribution and history of cigarette smoking.

Selvasekar CR, Cima RR, Larson DW, Dozois EJ, Harrington JR, Harmsen WS, Loftus EV, Sandborn WJ, Wolff BG, Pemberton JH. · Division of Colon and Rectal Surgery, Mayo Clinic, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. · J Am Coll Surg. · Pubmed #17481518 No free full text.

Abstract: BACKGROUND: Total proctocolectomy and ileal pouch anal anastomosis (IPAA) is the preferred operation for patients with chronic ulcerative colitis (CUC) refractory to medical therapy. Infliximab (IFX), an antitumor necrosis factor-alpha antibody, has demonstrated efficacy in medical management of CUC. The aim of this study is to determine if IFX before IPAA impacts short-term outcomes. STUDY DESIGN: A prospective institutional database was retrospectively reviewed for short-term complications after IPAA for CUC. Postoperative outcomes were compared between patients who received pre-IPAA IFX and those who did not. RESULTS: Between 2002 and 2005, 47 patients received IFX before IPAA, and 254 patients received none. There were no gender (p = 0.16) or body mass index (p = 0.07) differences between groups. IFX patients were younger than non-IFX patients (mean age 28.1 to 39.3 years) (p < 0.001). In IFX patients, 70% were receiving preoperative IFX, azathioprine, and corticosteroids. Mortality was nil. Overall surgical morbidity was similar: 61.7% and 48.8%, IFX and non-IFX, respectively (p = 0.10). Anastomotic leaks (p = 0.02), pouch-specific (p = 0.01) and infectious (p < 0.01) complications were more common in IFX patients. Multivariable analysis revealed IFX as the only factor independently associated with infectious complications (odds ratio [OR] = 3.5; CI, 1.6-7.5). In a separate analysis, incorporating age, high-dose corticosteroids, azathioprine, and severity of colitis, IFX remained significantly associated with infectious complications (OR = 2.7; CI, 1.1-6.7). CONCLUSIONS: CUC patients treated with IFX before IPAA have substantially increased the odds of postoperative pouch-related and infectious complications. Additional prospective studies are required to determine if IFX alone or other factors contribute to the observed increases in infectious complications.

Loftus CG, Loftus EV, Harmsen WS, Zinsmeister AR, Tremaine WJ, Melton LJ, Sandborn WJ. · Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. · Inflamm Bowel Dis. · Pubmed #17206702 links to  free full text

Abstract: BACKGROUND: We previously reported that the prevalence of Crohn's disease (CD) and ulcerative colitis (UC) in Olmsted County, Minnesota, had risen significantly between 1940 and 1993. We sought to update the incidence and prevalence of these conditions in our region through 2000. METHODS: The Rochester Epidemiology Project allows population-based studies of disease in county residents. CD and UC were defined by previously used criteria. County residents newly diagnosed between 1990 and 2000 were identified as incidence cases, and persons with these conditions alive and residing in the county on January 1, 2001, were identified as prevalence cases. All rates were adjusted to 2000 US Census figures for whites. RESULTS: In 1990-2000 the adjusted annual incidence rates for UC and CD were 8.8 cases per 100,000 (95% confidence interval [CI], 7.2-10.5) and 7.9 per 100,000 (95% CI, 6.3-9.5), respectively, not significantly different from rates observed in 1970-1979. On January 1, 2001, there were 220 residents with CD, for an adjusted prevalence of 174 per 100,000 (95% CI, 151-197), and 269 residents with UC, for an adjusted prevalence of 214 per 100,000 (95% CI, 188-240). CONCLUSION: Although incidence rates of CD and UC increased after 1940, they have remained stable over the past 30 years. Since 1991 the prevalence of UC decreased by 7%, and the prevalence of CD increased about 31%. Extrapolating these figures to US Census data, there were approximately 1.1 million people with inflammatory bowel disease in the US in 2000.

Loftus EV. · Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. · Inflamm Bowel Dis. · Pubmed #17119384 links to  free full text

Abstract: A large, Internet-based survey of a random sample of members of the Crohn's and Colitis Foundation of America was undertaken to gain knowledge and understanding of patients' experiences with ulcerative colitis and first-line therapies. From 49,410 invitations to participate, 1,595 usable responses were received from patients with ulcerative colitis. Patients were prescribed a range of aminosalicylates for their ulcerative colitis. Treatments with the highest proportion of satisfied patients were associated with highest remission rates. Forty-three percent of patients considered their disease to be in remission; however, 74% reported disease relapse during the previous 12 months. Over 60% of patients reported that they were noncompliant with prescribed aminosalicylate dosing schedules, with reasons attributed to frequency of dosing, the number of pills, and the inconvenience of the medication. Many respondents reported that they had made significant lifestyle changes because of their ulcerative colitis, including spending more time at home (46%) and participating in fewer social activities (37%). When asked to describe their ideal treatment, patients considered high efficacy (97%), lack of side effects (74%), nonparenteral dosing (46%), nonrectal dosing (36%), low cost (23%), fewer pills (23%), and less frequent dosing (23%) as "very important." This study demonstrates that continuous symptomatic remission is central to patient satisfaction and that patients find currently available aminosalicylates to be inconvenient. Patients' ideal therapy would be an effective, oral formulation with fewer tablets, less frequent dosing, and minimal side effects. Development of such a therapy would, therefore, potentially improve both patient compliance and overall treatment success.

Tung J, Loftus EV, Freese DK, El-Youssef M, Zinsmeister AR, Melton LJ, Harmsen WS, Sandborn WJ, Faubion WA. · Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. · Inflamm Bowel Dis. · Pubmed #17119382 links to  free full text

Abstract: BACKGROUND: The goal of this study was to examine the 1-year outcome after the first course of systemic corticosteroids in an inception cohort of pediatric patients with inflammatory bowel disease. METHODS: All Olmsted County (Minnesota) residents diagnosed with Crohn's disease (n = 50) or ulcerative colitis (n = 36) before 19 years of age from 1940 to 2001 were identified. Outcomes at 30 days and 1 year after the initial course of corticosteroids were recorded. RESULTS: Twenty-six patients with Crohn's disease (65%) and 14 with ulcerative colitis (44%) were treated with corticosteroids before age 19. Thirty-day outcomes for corticosteroid-treated Crohn's disease were complete remission in 16 (62%), partial remission in 7 (27%), and no response in 3 (12%), with 2 of these patients requiring surgery. Thirty-day outcomes for treated ulcerative colitis were complete remission in 7 (50%), partial remission in 4 (29%), and no response in 3 (21%). One-year outcomes for Crohn's disease were prolonged response in 11 (42%) and corticosteroid dependence in 8 (31%), whereas 7 (27%) were postsurgical. One-year outcomes for ulcerative colitis were prolonged response in 8 (57%) and corticosteroid dependence in 2 (14%), whereas 4 (29%) were postsurgical. CONCLUSIONS: Most pediatric patients with inflammatory bowel disease initially responded to corticosteroids. However, after 1 year, 58% of pediatric patients with Crohn's disease and 43% of pediatric patients with ulcerative colitis either were steroid dependent or required surgery. This finding emphasizes the need for early steroid-sparing medications in pediatric inflammatory bowel disease.

Regueiro M, Loftus EV, Steinhart AH, Cohen RD. · Inflammatory Bowel Disease Center and Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. · Inflamm Bowel Dis. · Pubmed #17012969 links to  free full text

Abstract: BACKGROUND: The goal of this work was to critically evaluate the published studies on the treatment of ulcerative proctitis (UP) and left-sided ulcerative colitis (L-UC). The results of this review provided the content for the accompanying treatment guidelines, Clinical Guidelines for the Medical Management of Left-sided Ulcerative Colitis and Ulcerative Proctitis: Summary Statement. METHODS: All English language articles published between 1995 and September 2005 were identified through a comprehensive literature search using OVID and PubMed. The quality of the data supporting or rejecting the use of specific therapies was categorized by a data quality grading scale. An "A+" grade was assigned to treatment supported by multiple high-quality randomized controlled trials with consistent results, whereas a "D" grade was given to therapy supported only by expert opinion. The therapeutic efficacy of a treatment was defined by its success in treating UP and L-UC compared with placebo. A medication was ranked as "excellent" if it was specifically studied for UP and L-UC and had consistently positive results compared with placebo or another agent. Quality and efficacy scores were agreed on by author consensus. RESULTS: For the acute treatment of UP or L-UC, the rectally administered corticosteroids and mesalazine (5-ASA), either alone or in combination with oral 5-ASAs, are the most effective therapy: evidence quality, A+; efficacy, excellent. Only rectally administered 5-ASA received an A+/excellent rating for maintenance of remission. Infliximab received an A+ grade for induction and maintenance of remission but only a "good" rating because the studies were performed in all UC, not specifically UP or L-UC. CONCLUSIONS: This critical evaluation of treatment provides a "report card" on medications available for the management of patients with UP and L-UC. The guidelines should provide a useful reference and supplement for physicians treating UC patients.

Regueiro M, Loftus EV, Steinhart AH, Cohen RD, Anonymous00130. · Inflammatory Bowel Disease Center and Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. · Inflamm Bowel Dis. · Pubmed #17012968 links to  free full text

Abstract: There are few published guidelines for the treatment of inflammatory bowel disease. Physicians choose therapy based on evidence-based data, peer and expert opinion, and personal experience. This article provides treatment guidelines for the induction and maintenance of ulcerative proctitis and left-sided colitis and the management of disease refractory to 5-aminosalicylic acid (5-ASA) compounds and corticosteroids The guidelines are derived from evidence-based data and, when lacking, expert opinion or the authors' experience. The comprehensive review of the literature is presented in the accompanying article, "The Medical Management of Left-Sided Ulcerative Colitis and Ulcerative Proctitis: Critical Evaluation of Therapeutic Trials". Rectally administered 5-ASA and corticosteroid suppositories are effective treatment for most ulcerative proctitis patients. Corticosteroid and 5-ASA enemas, which reach the splenic flexure of the colon, are recommended for patients with left-sided ulcerative colitis. The combination of rectally administered 5-ASA enemas and oral 5-ASA agents may afford better treatment of left-sided colitis and possibly prevent proximal extension of disease. Patients refractory to 5-ASAs and corticosteroids may require an immunomodulator or biological response modifier therapy. Those who have ongoing signs and symptoms of ulcerative proctitis and left-sided ulcerative colitis despite maximal medical therapy require a proctocolectomy.