Global Health Education in Gastroenterology Fellowship: A National Survey.

BACKGROUND: Interest in global health (GH) education is increasing across disciplines. AIMS: To assess exposure to and perception of GH training among gastroenterology fellows and program directors across the USA. METHODS: Design: Electronic survey study. SETTING: The questionnaire was circulated to accredited US gastroenterology fellowship programs, with the assistance of the American Gastroenterological Association. PARTICIPANTS: Gastroenterology program directors and fellows. RESULTS: The questionnaire was returned by 127 respondents (47 program directors, 78 fellows) from 55 training programs (36 % of all training programs). 61 % of respondents had prior experience in GH. 17 % of programs offered GH curriculum with international elective (13 %), didactic (9 %), and research activity (7 %) being the most common. Fellows had adequate experience managing hepatitis B (93 %), cholangiocarcinoma (84 %), and intrahepatic duct stones (84 %). 74, 69 and 68 % reported having little to no experience managing hepatitis E, tuberculosis mesenteritis, or epidemic infectious enteritis, respectively. Most fellows would participate in an elective in an underserved area locally (81 %) or a 4-week elective abroad (71 %), if available. 44 % of fellows planned on working or volunteering abroad after fellowship. Barriers to establishing GH curriculum included funding (94 %), scheduling (88 %), and a lack of standardized objectives (78 %). Lack of interest, however, was not a concern. Fellows (49 %), more than faculty (29 %) (χ 2 = 21.9; p = 0.03), believed that GH education should be included in fellowship curriculum. CONCLUSIONS: Program directors and trainees recognize the importance of GH education. However, only 17 % of ACGME-approved fellowship programs offer the opportunity. Global health curriculum may enhance gastroenterology training.

Prospective Evaluation of Terminal Ileitis in a Surveillance Population of Patients with Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is a disease that is normally limited to involvement of the colon. Terminal ileitis in patients with UC with only inactive or mildly active disease has never been investigated. The aim of this prospective study was to determine the prevalence and significance of ileitis among patients with UC enrolled in an endoscopic surveillance program. METHODS: The study consisted of 72 patients with UC and 90 healthy controls who underwent surveillance and screening colonoscopy, respectively. The endoscopic and histologic features of the terminal ileum (both groups) and colon (UC group only) were evaluated in a standardized fashion. Extensive clinical and endoscopic information was obtained from the subjects, and these data were compared between patients with UC either with or without ileitis. RESULTS: Sixteen of 72 patients with UC (22%) had ileitis compared to only 4 of 90 (4%) of the non-UC controls (P < 0.001). None of the patients had features of backwash. Among patients with UC, the presence of ileitis showed a trend towards correlation with extent of disease, but a significant association with involvement of the colonic side of the ileocecal valve (P = 0.02) was noted. Alcohol use in the week before the colonoscopy was also significant (P = 0.02). There were no other features that were significantly related to ileitis in the patients with UC. Only one UC case with ileitis developed Crohn's disease on follow-up. CONCLUSIONS: Ileitis in patients with UC may represent a primary extracolonic manifestation of UC in patients with inactive or mild disease and is not due to backwash.

Blood-based biomarkers used to predict disease activity in Crohn's disease and ulcerative colitis.

BACKGROUND: Identifying specific genes that are differentially expressed during inflammatory bowel disease flares may help stratify disease activity. The aim of this study was to identify panels of genes to be able to distinguish disease activity in Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Patients were grouped into categories based on disease and severity determined by histological grading. Whole blood was collected by PAXgene Blood RNA collection tubes, (PreAnalytiX) and gene expression analysis using messenger RNA was conducted. Logistic regression was performed on multiple combinations of common probe sets, and data were evaluated in terms of discrimination by computing the area under the receiving operator characteristic curve (ROC-AUC). RESULTS: Nine inactive CD, 8 mild CD, 10 moderate-to-severe CD, 9 inactive UC, 8 mild UC, 10 moderate-to-severe UC, and 120 controls were hybridized to Affymetrix U133 Plus 2 microarrays. Panels of 6 individual genes discriminated the stages of disease activity: CD with mild severity {ROC-AUC, 0.89 (95% confidence interval [CI], 0.84%-0.95%)}, CD with moderate-to-severe severity (ROC-AUC 0.98 [95% CI, 0.97-1.0]), UC with mild severity (ROC-AUC 0.92 [95% CI, 0.87-0.96]), and UC with moderate-to-severe severity (ROC-AUC 0.99 [95% CI, 0.97-1.0]). Validation by real-time reverse transcription-PCR confirmed the Affymetrix microarray data. CONCLUSIONS: The specific whole blood gene panels reliably distinguished CD and UC and determined the activity of disease, with high sensitivity and specificity in our cohorts of patients. This simple serological test has the potential to become a biomarker to determine the activity of disease.

High self-efficacy predicts adherence to surveillance colonoscopy in inflammatory bowel disease.

BACKGROUND: Patients with extensive ulcerative colitis or Crohn's disease of the colon have an increased risk of colon cancer and require colonoscopic surveillance. In this study, we assessed individual self-efficacy (SE) to estimate the probability of adherence to surveillance colonoscopies. METHODS: Three hundred seventy-eight patients with ulcerative colitis or Crohn's disease of the colon for at least 7 years and with at least one third of the colon involved participated in this cross-sectional questionnaire study performed at 3 tertiary referral inflammatory bowel disease clinics. Medical charts were abstracted for demographic and clinical variables. The questionnaire contained a group of items assessing SE for undergoing colonoscopy. RESULTS: We validated our 20-question SE scale and used 8 of the items that highlighted scheduling, preparation, and postprocedure recovery, to develop 2 shorter SE scales. All 3 scales were reliable with Cronbach's α ranging from 0.845 to 0.905 and correlated with chart-documented adherence to surveillance colonoscopy (P < 0.001). We then developed logistic regression models to predict adherence to surveillance colonoscopy using each scale separately along with other key variables (i.e., disease location, knowledge of correct adherence intervals, and information sources of patients consulted regarding Crohn's disease and ulcerative colitis) and demonstrated model accuracy up to 74%. CONCLUSIONS: SE, as measured by our validated scales, correlates with chart-adherence to surveillance colonoscopy. Our adherence model, which includes SE, predicts adherence with 74% certainty. An 8-item validated clinical questionnaire can be administered to assess whether patients in this population may require further intervention for adherence.

Factors that affect adherence to surveillance colonoscopy in patients with inflammatory bowel disease.

BACKGROUND: Patients with extensive ulcerative colitis or Crohn's disease of the colon have an increased risk of colon cancer and require colonoscopic surveillance. This study explores factors that affect adherence to surveillance colonoscopy. METHODS: Three hundred and seventy-eight patients with ulcerative colitis or Crohn's disease of the colon for at least 7 years and at least one-third of the colon involved participated in this cross-sectional questionnaire study performed at 3 tertiary referral inflammatory bowel disease clinics. RESULTS: Two hundred and eight patients were female and 189 had ulcerative colitis. The mean age was 49.9 years and mean disease duration 22.9 years. The total number of surveillance colonoscopies performed was 1529, and the mean number per patient was 4.01. The mean interval between surveillance colonoscopies was 2.71 years; 282 patients had a mean interval of <3 years. Self-reported adherence was consistently higher than chart-documented adherence. Significant categories of reasons for nonadherence were logistics (P = 0.012), health perceptions (P = 0.0001); stress regarding procedure, job, or personal life (P = 0.0002); and procedure problems (P = 0.001). The most frequently cited most important reason was difficulty with the bowel preparation (18 patients; 4.8%). Of the 26 patients with inflammatory bowel disease-related dysplasia, 3 had cancer, 4 high-grade dysplasia, 15 low-grade dysplasia, and 4 indefinite dysplasia. Detection of dysplasia was not related to adherence or to lack of adherence. CONCLUSIONS: In this study, 25.5% of our patients underwent surveillance colonoscopies at >3-year intervals on average. Significant categories of reasons for nonadherence included logistics, health perceptions, stress, and procedure problems.

Doctor message can alter patients' behavior and attitudes regarding inflammatory bowel disease and colon cancer.

BACKGROUND: Patients with extensive ulcerative (UC) or Crohn's (CD) colitis have an increased risk of colon cancer and require colonoscopic surveillance. This study explores patient attitudes and behavior regarding inflammatory bowel disease (IBD), colonoscopies, and colon cancer risk. METHODS: In all, 514 patients with UC or CD colitis for at least 7 years and at least one-third of the colon involved participated in this cross-sectional questionnaire study performed at three tertiary referral IBD clinics. RESULTS: In all, 288 patients were female, 262 had UC, and 252 had CD. The mean age was 48 (range, 20-88) and mean number of years with symptoms was 20 (range, 7-51); 70.8% reported "my doctor" as an extensive information source. The mean perceived lifetime risk of developing colon cancer without having routine colonoscopies was 56% (SD 24.193). We developed and validated a scale of 10 important messages that IBD patients remember doctors discussing with them ("Doctor Told Scale"). Higher scores correlated with better quality of life (P < 0.001) and positive descriptors of colonoscopies and IBD (P < 0.001). Patients with higher scores perceived a higher chance of getting colon cancer without having surveillance colonoscopies (P < 0.001) and were more likely to report that the correct surveillance interval is every 2 years (P < 0.01). CONCLUSIONS: Patients who remember their doctor's messages are more likely to have a positive outlook about colonoscopies and IBD, have a better quality of life, undergo surveillance colonoscopies at the correct interval, and perceive cancer risk more realistically.

Blood-based biomarkers can differentiate ulcerative colitis from Crohn's disease and noninflammatory diarrhea.

BACKGROUND: Blood gene expression profiling has been used in several studies to identify patients with a number of conditions and diseases. A blood test with the ability to differentiate Crohn's disease (CD) from ulcerative colitis (UC) and noninflammatory diarrhea would be useful in the clinical management of these diseases. METHODS: Affymetrix U133Plus 2.0 GeneChip oligonucleotide arrays were used to generate whole blood gene expression profiles for 21 patients with UC, 24 patients with CD, and 10 control patients with diarrhea, but without colonic pathology. RESULTS: A supervised learning method (logistic regression) was used to identify specific panels of probe sets which were able to discriminate between UC and CD and from controls. The UC panel consisted of the four genes, CD300A, KPNA4, IL1R2, and ELAVL1; the CD panel comprised the four genes CAP1, BID, NIT2, and NPL. These panels clearly differentiated between CD and UC. CONCLUSIONS: Gene expression profiles from blood can differentiate patients with CD from those with UC and from noninflammatory diarrheal disorders.

Differential regulation of peripheral leukocyte genes in patients with active Crohn's disease and Crohn's disease in remission.

GOALS: Assessment of disease severity is a frequent challenge in the management of Crohn's disease. Noninvasive, accurate markers for monitoring disease activity are urgently required. Specific gene expression patterns and molecular biomarkers associated with active Crohn's disease could serve as such markers, thereby providing a novel approach to disease activity monitoring. BACKGROUND: Gene expression profiling in circulating leukocytes has shown promise in several medical conditions and blood may provide an easily accessible surrogate tissue for using gene expression profiling to assess activity of Crohn's disease. STUDY: In this study, we compared genome-wide transcription profiles of circulating leukocytes in patients with active and quiescent Crohn's disease. RESULTS: We observed complex changes in blood gene expression patterns in active Crohn's disease: genes of various functional categories were differentially regulated between active and inactive Crohn's disease. We specifically identified a number of inflammatory molecules overexpressed or underexpressed in active Crohn's disease and validated a subset of these genes by real-time reverse transcription-polymerase chain reaction. CONCLUSIONS: The genes differentially regulated in peripheral leukocytes represent potential new biomarkers for assessing the activity of Crohn's disease.

Fulminant hepatic failure secondary to erlotinib.

Erlotinib is a tyrosine kinase inhibitor recently approved by the Food and Drug Administration for the treatment of non-small-cell lung cancer and pancreatic cancer. We report a case of a patient with stage IV non-small-cell lung cancer who died of fulminant hepatic failure as a result of treatment with erlotinib.

5-aminosalicylate therapy is associated with higher 6-thioguanine levels in adults and children with inflammatory bowel disease in remission on 6-mercaptopurine or azathioprine.

BACKGROUND: Small uncontrolled trials have suggested that 5-aminosalicylate (5-ASA) medications increase 6-thioguanine nucleotide (6-TGn) levels in adults with Crohn's disease (CD) on azathioprine (AZA) or 6-mercaptopurine (6-MP), presumably through the inhibition of thiopurine methyltransferase (TPMT). We tested the theory that coadministration of 5-ASA agents with AZA/6-MP results in higher 6-TGn levels in a large cohort of children and adults with CD or ulcerative colitis (UC). METHODS: A retrospective cohort study identified all children and adults treated for IBD with AZA/6-MP at 2 tertiary medical centers. Patients were included if their TPMT genotype was known and 6-TGn and 6-methymercaptopurine (6-MMP) levels had been obtained after 3 months of clinical remission at a stable dose of AZA/6-MP. 6-TGn and 6-MMP levels were compared between patients taking and those not taking 5-ASA medications through the use of linear regression models to identify and adjust for potentially confounding variables. RESULTS: Of the 126 patients included, 88 were taking 5-ASA medications. Patients on 5-ASA agents had higher mean 6-TGn levels after adjustment for confounding variables (Delta6-TGn, 47.6 +/- 21.8 pmol/8 x 10 red blood cells; P = 0.03). CD and TPMT heterozygosity was independently associated with higher 6-TGn levels (P = 0.01 and P = 0.03, respectively). 5-ASA exposure was not associated with a change in 6-MMP levels. CONCLUSIONS: We found that 5-ASA therapy is associated with higher 6-TGn levels in children and adults with IBD on 6-MP/AZA. TPMT inhibition may not explain this effect because 5-ASA exposure did not affect 6-MMP levels. The observed association of CD with higher 6-TGn levels is novel and needs to be verified in prospective studies.