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Background & Aims Studies are needed to determine the mechanisms of mucosal dysregulation in patients with inflammatory bowel diseases (IBDs) and differences in inflammatory responses of patients with ulcerative colitis (UC) vs Crohn’s disease (CD). We used mass cytometry (CyTOF) to characterize and compare immune cell populations in the mucosa and blood from patients with IBD and without IBD (controls) at single-cell resolution. Methods We performed CyTOF analysis of colonic mucosa samples (n = 87) and peripheral blood mononuclear cells (n = 85) from patients with active or inactive UC or CD and controls. We also performed single-cell RNA sequencing, flow cytometry, and RNA in situ hybridization analyses to validate key findings. We used random forest modeling to identify differences in signatures across subject groups. Results Compared with controls, colonic mucosa samples from patients with IBD had increased abundances of HLA-DR+CD38+ T cells, including T-regulatory cells that produce inflammatory cytokines; CXCR3+ plasmablasts; and IL1B+ macrophages and monocytes. Colonic mucosa samples from patients with UC were characterized by expansion of IL17A+ CD161+ effector memory T cells and IL17A+ T-regulatory cells; expansion of HLA-DR+CD56+ granulocytes; and reductions in type 3 innate lymphoid cells. Mucosal samples from patients with active CD were characterized by IL1B+HLA-DR+CD38+ T cells, IL1B+TNF+IFNG+ naive B cells, IL1B+ dendritic cells (DCs), and IL1B+ plasmacytoid DCs. Peripheral blood mononuclear cells from patients with active CD differed from those of active UC in that the peripheral blood mononuclear cells from patients with CD had increased IL1B+ T-regulatory cells, IL1B+ DCs and IL1B+ plasmacytoid DCs, IL1B+ monocytes, and fewer group 1 innate lymphoid cells. Random forest modeling differentiated active UC from active CD in colonic mucosa and blood samples; top discriminating features included many of the cellular populations identified above. Conclusions We used single-cell technologies to identify immune cell populations specific to mucosa and blood samples from patients with active or inactive CD and UC and controls. This information might be used to develop therapies that target specific cell populations in patients with different types of IBD.

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-year intervals on average. Significant categories of reasons for nonadherence included logistics, health perceptions, stress, and procedure problems.

Interest in global health (GH) education is increasing across disciplines. To assess exposure to and perception of GH training among gastroenterology fellows and program directors across the USA. 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. 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. 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.

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. (Inflamm Bowel Dis 2012)

Diverticular disease has been considered a disease of the elderly, but recently, an increased incidence has been noted in younger patients. Diverticulosis is asymptomatic; however, when symptomatic, it is referred to as diverticular disease. When associated with any inflammation, it is diverticulitis. Diverticulitis is an acute illness, but symptoms may become chronic with recurrent episodes. When mucosal inflammation is present, segmental colitis associated with diverticula (SCAD) is identified. SCAD is a distinct, but uncommon, disorder sharing histological and clinical features of ulcerative colitis and Crohn disease. Only 1 to 2% of patients with diverticulosis will develop diverticulitis. This review covers the epidemiology, etiology and genetics, pathophysiology and pathogenesis, diagnosis, management, complications and prognosis of diverticulosis, and diverticulitis. Figures show diverticulosis, symptomatic uncomplicated diverticular disease, diverticulitis, computed tomography scan of acute diverticulitis, and a management algorithm. Tables list definitions, risk factors, pathophysiology, modified Hinchey classification, and acute diverticulitis differential diagnosis. This review contains 5 highly rendered figures, 5 tables and 105 references

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.

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.

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.

The authors measured gastric emptying in 13 patients undergoing radiation therapy to the chest, abdomen, or pelvis for nongastrointestinal cancer to investigate whether gastric emptying (GE) was altered by this therapy. Symptoms and weight were monitored at regular intervals. Patients served as their own controls and were compared to a group of healthy subjects. When studied prior to radiation therapy (baseline), cancer patients had a gastric emptying rate that was similar to a healthy control group (t1/2 mean+/-SEM 92.0+/-15.3 vs. 80.4+/-8.2 min). Irradiation did not change the emptying rate, either after the first dose (early) of 180 cGy (t1/2 99.5+/-17.9) or after 2 weeks of therapy (late) with 3000 cGy (t1/2 75.5+/-7.3). There was no correlation of radiation field or tumor type with gastric emptying rate. Two of the 13 patients experienced nausea and vomiting during their course of radiation, but their gastric emptying was unchanged from baseline.

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. (Inflamm Bowel Dis 2011;)

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.

Use of a Standardized Clinical Assessment and Management Plan to Demonstrate Barriers to Trough Level and Antibody Level Testing in Patients on Anti-Tumor Necrosis Factor Therapy for Inflammatory Bowel Disease Edward L. Barnes, Jonathan S. Levine, Vikas Pabby, George Ciociolo, Roya Ghazinouri, Jeffery O. Greenberg, Karl Laskowski, Sarah R. McLaughlin, Dionne Graham, Peter A. Banks, Michael Currier, Punyanganie S. de Silva, Sonia Friedman, Matthew J. Hamilton, Joshua R. Korzenik, Frederick L. Makrauer, Beth-Ann Norton, Scott B. Snapper, Michal Tomczak, Robert Burakoff

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.

Persistent duodenal stenosis has been noted as a complication of chronic pancreatitis, but its clinical importance and histologic basis have not been defined. We report three patients with chronic alcoholic pancreatitis who developed duodenal stenosis and intractable abdominal pain. In two patients, the stenosis was caused by severe inflammation of pancreatic tissue within the wall of the duodenum. Pancreaticoduodenectomy resulted in prompt and sustained clinical improvement in both patients. In the third patient, who had mural inflammation in the distal stomach and presumably in the duodenum as well, vagotomy and gastrojejunostomy relieved severe duodenal obstruction but not pain. This study supports the view that duodenal stenosis is caused by severe intramural duodenal inflammation and suggests that a pancreaticoduodenectomy may be required for relief of pain.

A 14-year-old boy accidentally swallowed a partial denture fabricated of radiolucent acrylic material. A young boy accidentally ingested a partial denture. Although the denture was finally extracted easily from the stomach with a fiberoptic endoscope, diagnostic confusion did occur because the denture was made of radiolucent acrylic material. The need for the use of radiopaque denture material is emphasized, and the efficacy of the fiberoptic endoscope in the removal of ingested dental prostheses is outlined.

A 48-year-old woman with malabsorption and type V hyperlipoproteinemia developed hypervitaminosis A with a total plasma vitamin A level of 871 micrograms/dL during therapy with an oral dosage of 18,000 retinol equivalents (60,000 IU) daily. Twelve percent of the total plasma retinol was found to be transported in the chylomicron-very low density lipoprotein (VLDL) fraction, which does not contain retinol-binding protein. For comparison, concentrations of retinyl esters and retinol were determined in nine patients with type V hyperlipoproteinemia and nine control subjects, none of whom were using vitamin A supplements. Both retinyl esters and retinol were significantly elevated in the group with hyperlipoproteinemia (p less than 0.0005 in both cases). Eight of these nine patients had retinol present in the chylomicron-VLDL fraction, whereas retinol was not detectable in this fraction in any of the nine normal controls. The data suggest that patients with severe hypertriglyceridemia associated with type V hyperlipoproteinemia are at increased risk for hypervitaminosis A.