Christina Bannert

Sex-Specific Prevalence of Adenomas, Advanced Adenomas, and Colorectal Cancer in Individuals Undergoing Screening Colonoscopy

CONTEXT Although some studies have shown that men are at greater age-specific risk for advanced colorectal neoplasia than women, the age for referring patients to screening colonoscopy is independent of sex and usually recommended to be 50 years. OBJECTIVE To determine and compare the prevalence and number needed to screen (NNS) for adenomas, advanced adenomas (AAs), and colorectal carcinomas (CRCs) for different age groups in men and women. DESIGN, SETTING, AND PATIENTS Cohort study of 44,350 participants in a national screening colonoscopy program over a 4-year period (2007 to 2010) in Austria. MAIN OUTCOME MEASURES Prevalence and NNS of adenomas, AAs, and CRCs in different age groups for men and women. RESULTS The median ages were 60.7 years (interquartile range [IQR], 54.5-67.5 years) for women and 60.6 years (IQR, 54.3-67.6 years) for men, and the sex ratio was nearly identical (51.0% [22,598] vs 49.0% [21,572]). Adenomas were found in 19.7% of individuals screened (95% CI, 19.3%-20.1%; n = 8743), AAs in 6.3% (95% CI, 6.1%-6.5%; n = 2781), and CRCs in 1.1% (95% CI, 1.0%-1.2%; n = 491); NNS were 5.1 (95% CI, 5.0-5.2), 15.9 (95% CI, 15.4-16.5), and 90.9 (95% CI, 83.3-100.0), respectively. Male sex was significantly associated with a higher prevalence of adenomas (24.9% [95% CI, 24.3%-25.4%] vs 14.8% [95% CI, 14.3%-15.2%]; P < .001; unadjusted odds ratio [OR], 1.9 [95% CI, 1.8-2.0]), AAs (8.0% [95% CI, 7.6%-8.3%] vs 4.7% [95% CI, 4.4%-4.9%]; P < .001; unadjusted OR, 1.8 [95% CI, 1.6-1.9]), and CRCs (1.5% [95% CI, 1.3%-1.7%] vs 0.7% [95% CI, 0.6%-0.9%]; P < .001; unadjusted OR, 2.1 [95% CI, 1.7-2.5]). The prevalence of AAs in 50- to 54-year-old individuals was 5.0% (95% CI, 4.4%-5.6%) in men but 2.9% (95% CI, 2.5%-3.4%) in women (adjusted P = .001); the NNS in men was 20 (95% CI, 17.8-22.6) vs 34 in women (95% CI, 29.1-40; adjusted P = .001). There was no statistical significance between the prevalence and NNS of AAs in men aged 45 to 49 years compared with women aged 55 to 59 years (3.8% [95% CI, 2.3%-6.1%] vs 3.9% [95% CI, 3.3%-4.5%] and 26.1 [95% CI, 16.5-44.4] vs 26 [95% CI, 22.5-30.2]; P = .99). CONCLUSION Among a cohort of Austrian individuals undergoing screening colonoscopy, the prevalence and NNS of AAs were comparable between men aged 45 to 49 years and women aged 55 to 59 years.

Sedation in Screening Colonoscopy: Impact on Quality Indicators And Complications

OBJECTIVES:Quality indicators including cecal intubation rate (CIR) and adenoma detection rate (ADR) are established. Sex differences of quality indicators are observed, but the influence of sedation has not been investigated so far. The objective of this study is to assess the impact of sedation on quality indicators, including CIR and ADR, according to sex.METHODS:We analyzed data of 52,506 screening colonoscopies performed by 196 endoscopists between November 2007 and April 2011 according to the Austrian “quality management for colon cancer prevention” program.RESULTS:Sedation did not affect polyp detection rate (women P=0.7972, men P=0.3711) or ADR for both sexes (women P=0.2773, men P=0.8676). ADR was not significantly influenced by sedation (P=0.1272), but by age and sex (both P<0.0001), when the executing endoscopist was considered. Although women were more often sedated than men (90.70 vs. 81.83%; P<0.0001), CIR was slightly lower in women than in men (94.69 vs. 96.58%; P<0.0001). Sedation improved the CIR in women by 2.95% (94.96 vs. 92.01%; P<0.0001), whereas in men it was just by 1.28% (96.81 vs. 95.53%; P<0.0001). Sedated women only reached the CIR of unsedated men (94.96 vs. 95.53%; P=0.1005). Accounting for the intra-observer influence of the endoscopist, the overall CIR was influenced by the interaction of sex and age (P=0.0049), but not by sedation (P=0.1435).CONCLUSIONS:Sedation does not increase adenoma or polyp detection, although it leads to an increase in CIR in men and women. This effect is more pronounced in women, yet CIR of men remains higher compared with women. Quality indicators are mainly influenced by the patients age, sex, and the endoscopists’ individual performance, rather than the endoscopists’ subspeciality or procedural experience.

Preventive sublingual immunotherapy in preschool children: first evidence for safety and pro-tolerogenic effects.

Prevention of new IgE sensitizations has been described during allergen‐specific immunotherapy. However, prospective data using a preventive approach in very young children who would benefit most are missing. We initiated a prospective pilot study investigating the safety, immunomodulatory, and sensitization‐preventive effect of sublingual immunotherapy (SLIT) in mono/oligoclonally sensitized, clinically asymptomatic children 2–5 yr of age.

Impact of systemic immuno-suppression after solid organ transplantation on allergen-specific responses

To cite this article: Eiwegger T, Gruber S, Geiger C, Mayer E, Dehlink E, Bannert C, Frischer T, Kasper D, Jaksch P, Klepetko W, Akdis C, Szépfalusi Z. Impact of systemic immuno‐suppression after solid organ transplantation on allergen‐specific responses. Allergy 2011; 66: 271–278.

Cord Blood Derived CD4+CD25high T Cells Become Functional Regulatory T Cells upon Antigen Encounter

Background: Upon antigen exposure, cord blood derived T cells respond to ubiquitous environmental antigens by high proliferation. To date it remains unclear whether these “excessive” responses relate to different regulatory properties of the putative T regulatory cell (Treg) compartment or even expansion of the Treg compartment itself. Methods: Cord blood (>37 week of gestation) and peripheral blood (healthy controls) were obtained and different Treg cell subsets were isolated. The suppressive potential of Treg populations after antigen exposure was evaluated via functional inhibition assays ([3H]thymidine incorporation assay and CFSE staining) with or without allergen stimulation. The frequency and markers of CD4+CD25highFoxP3+ T cells were characterized by mRNA analysis and flow cytometry. Results: Cord blood derived CD4+CD25high cells did not show substantial suppressor capacity upon TCR activation, in contrast to CD4+CD25high cells freshly purified from adult blood. This could not be explained by a lower frequency of FoxP3+CD4+CD25highcells or FOXP3 mRNA expression. However, after antigen-specific stimulation in vitro, these cells showed strong proliferation and expansion and gained potent suppressive properties. The efficiency of their suppressive capacity can be enhanced in the presence of endotoxins. If T-cells were sorted according to their CD127 expression, a tiny subset of Treg cells (CD4+CD25+CD127low) is highly suppressive even without prior antigen exposure. Conclusion: Cord blood harbors a very small subset of CD4+CD25high Treg cells that requires antigen-stimulation to show expansion and become functional suppressive Tregs.

Fc-Epsilon-RI, the High Affinity IgE-Receptor, Is Robustly Expressed in the Upper Gastrointestinal Tract and Modulated by Mucosal Inflammation

Background The role of the high affinity IgE receptor, FcεRI, in IgE-mediated immune responses of the gastrointestinal (GI) mucosa is poorly understood. Currently, a detailed characterization of FcεRI expression throughout the human gut is lacking. The aim of this study was to define the expression pattern of FcεRI in the GI tract. Methods/Principal Findings We compared FcεRI expression in children with gastritis/esophagitis (n = 10), celiac disease (n = 10), inflammatory bowel disease (IBD) (n = 9), and normal mucosa (n = 5). The α–subunit of FcεRI (FcεRIα), detected by immunohistochemistry, was found on cells infiltrating the mucosa of the esophagus, the stomach, and the duodenum, but was rarely detected in more distal sections of the GI tract. Accordingly, quantitative RT-PCR analysis on esophagus, stomach, duodenum, colon, and rectum biopsies revealed that FcεRIα and -β expression levels decreased towards the distal intestine. mRNA transcripts of the common Fc-receptor-γ chain were present in the entire GI mucosa. Double-immunofluorescence staining of esophageal specimens confirmed that FcεRIα was expressed on intraepithelial mast cells and Langerhans cells. The mRNA expression levels of the α, β, and γ subunits of FcεRI did not correlate with total serum IgE but were associated with mucosal inflammation. Conclusion/Significance Our data define the upper GI tract as the main site for IgE-mediated immune activation via FcεRI. Tissue mRNA levels of FcεRIα are regulated by inflammatory conditions rather than serum IgE, indicating that FcεRI might also play a role in pathologies other than allergy.

The Induction of IL-33 in the Sinus Epithelium and Its Influence on T-Helper Cell Responses

Background Chronic rhinosinusitis (CRS) is characterized by epithelial activation and chronic T-cell infiltration in sinonasal mucosa and nasal polyps. IL-33 is a new cytokine of the IL-1 cytokine family that has a pro-inflammatory and Th2 type cytokine induction property. The role of IL-33 in the pathomechanisms of CRS and its interaction with other T cell subsets remain to be fully understood. Methods The main trigger for IL-33 mRNA expression in primary human sinonasal epithelial cells was determined in multiple cytokine and T-cell stimulated cultures. The effects of IL-33 on naïve, Th0 and memory T-cells was studied by PCR, ELISA and flow cytometry. Biopsies from sinus tissue were analyzed by PCR and immunofluorescence for the presence of different cytokines and receptors with a special focus on IL-33. Results IL-33 was mainly induced by IFN-γ in primary sinonasal epithelial cells, and induced a typical CRSwNP Th2 favoring cytokine profile upon co-culture with T-helper cell subsets. IL-33 and its receptor ST2 were highly expressed in the inflamed epithelial tissue of CRS patients. While IL-33 was significantly up-regulated in the epithelium for CRSsNP, its receptor was higher expressed in sinus tissue from CRSwNP. Conclusions The present study delineates the influence of IL-33 in upper airway epithelium and a potential role of IL-33 in chronic inflammation of CRSwNP by enhancing Th2 type cytokine production, which could both contribute to a further increase of an established Th2 profile in CRSwNP.

High quality of screening colonoscopy in Austria is not dependent on endoscopist specialty or setting

BACKGROUND AND STUDY AIM International studies have shown differences in the outcome of screening colonoscopies related to the endoscopists specialty and setting of colonoscopy. The aim of this study was to investigate the impact of these two factors on quality parameters for screening colonoscopy in a quality-assured screening program. METHODS Adenoma detection rate (ADR), cecal intubation rate (CIR), polypectomy rate, flat polyp detection rate, carcinoma detection rate, sedation rate, complication rates, and other parameters of 59 901 screening colonoscopies performed by 178 endoscopists were analyzed in relation to specialty (35 gastroenterologists: 10 066 colonoscopies [16.8 %]; 84 nongastroenterologists: 26 271 colonoscopies [43.9 %]; 59 surgeons: 23 564 [39.3 %]), and setting (hospital: 12 580 [21.6 %] colonoscopies; office: 45 781 [78.4 %] colonoscopies). RESULTS The overall ADR was 20.5 % and the CIR was 95.6 %. The ADR did not show any statistical significance, either in relation to specialty or to setting. A significant difference in the CIR was found between hospital-based and office-based internists (98.5 % vs. 96.8 %, respectively; P  = 0.0005; odds ratio [OR] 2.2, 95 % confidence interval [CI] 1.4 - 3.4). Hospital-based internists had a significantly higher flat polyp detection rate (7.5 % vs. 4.1 %; P  = 0.02; OR 1.9, 95 %CI 1.1 - 3.2) and a significantly lower carcinoma detection rate (0.4 % vs. 0.6 %; P  = 0.03; OR 0.7, 95 %CI 0.5 - 1.0) compared with office-based internists. Complication rates were significantly lower among surgeons than among internists (0.1 % vs. 0.2 %; P  = 0.03; OR 0.5, 95 %CI 0.3 - 1.0). CONCLUSION Endoscopists participating in the Austrian quality assurance program offered high quality screening colonoscopy regardless of their specialty and setting. The implementation of a standardized quality program is therefore a decisive factor in quality improvement of screening colonoscopy.

Response to Shaikh et al.

To the Editor: We are thankful to Shaikh et al. (1) for their interest in our work and for sharing their data with us. Unfortunately, although withdrawal time is an important quality parameter, we do not have data on withdrawal time in our database. As our database started at the end of 2007 we also cannot tell you how many of these patients underwent repeated unsedated colonoscopy. However, we also think that it is an important issue that has to be addressed in future trials. Many patients in rural areas approach endoscopy units by car and prefer unsedated screening colonoscopy. In these cases, patients’ motivation to change from unsedated to sedated colonoscopy will be low, despite possible unpleasant memories of their previous colonoscopy. In our study, patients who received sedation during the procedure were included in the sedation group, and, unfortunately, cannot be analyzed separately (2). We do agree that changing from unsedated colonoscopy to sedated colonoscopy may increase the relative CIR in the sedation group, although we think that there is no need to discriminate if sedation is started at the beginning of the procedure or later to pass the fixed angulation of the colon. The median age in sedated and unsedated patients was the same (sedated 60.6 years (interquartile range: 54.3–67.5), unsedated 60.7 years (interquartile range: 54.4–67.9)).