Baseline Features and Reasons for Nonparticipation in the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) Study, a Colorectal Cancer Screening Trial.

Importance: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy. Objective: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors. Design, Setting, and Participants: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs medical centers between May 22, 2012, and December 1, 2017, with follow-up planned through 2028, comprised veterans aged 50 to 75 years with an average CRC risk and due for screening. Data were analyzed between March 7 and December 5, 2022. Exposure: Case report forms were used to capture enrolled participant data and reasons for declining participation among otherwise eligible individuals. Main Outcomes and Measures: Descriptive statistics were used to characterize the cohort overall and by intervention. Among individuals declining participation, logistic regression was used to compare preference for FOBT/FIT or colonoscopy by recruitment region and year. Results: A total of 50 126 participants were recruited (mean [SD] age, 59.1 [6.9] years; 46 618 [93.0%] male and 3508 [7.0%] female). The cohort was racially and ethnically diverse, with 748 (1.5%) identifying as Asian, 12 021 (24.0%) as Black, 415 (0.8%) as Native American or Alaska Native, 34 629 (69.1%) as White, and 1877 (3.7%) as other race, including multiracial; and 5734 (11.4%) as having Hispanic ethnicity. Of the 11 109 eligible individuals who declined participation (18.0%), 4824 (43.4%) declined due to a stated preference for a specific screening test, with FOBT/FIT being the most preferred method (2820 [58.5%]) vs colonoscopy (1958 [40.6%]; P < .001) or other screening tests (46 [1.0%] P < .001). Preference for FOBT/FIT was strongest in the West (963 of 1472 [65.4%]) and modest elsewhere, ranging from 199 of 371 (53.6%) in the Northeast to 884 of 1543 (57.3%) in the Midwest (P = .001). Adjusting for region, the preference for FOBT/FIT increased by 19% per recruitment year (odds ratio, 1.19; 95% CI, 1.14-1.25). Conclusions and Relevance: In this cross-sectional analysis of veterans choosing nonenrollment in the CONFIRM study, those who declined participation more often preferred FOBT or FIT over colonoscopy. This preference increased over time and was strongest in the western US and may provide insight into trends in CRC screening preferences.

Impact of withdrawal time on adenoma detection rate: results from a prospective multicenter trial.

BACKGROUND AND AIMS: Performing a high-quality colonoscopy is critical for optimizing the adenoma detection rate (ADR). Colonoscopy withdrawal time (a surrogate measure) of ≥6 minutes is recommended; however, a threshold of a high-quality withdrawal and its impact on ADR are not known. METHODS: We examined withdrawal time (excluding polyp resection and bowel cleaning time) of subjects undergoing screening and/or surveillance colonoscopy in a prospective, multicenter, randomized controlled trial. We examined the relationship of withdrawal time in 1-minute increments on ADR and reported odds ratio (OR) with 95% confidence intervals. Linear regression analysis was performed to assess the maximal inspection time threshold that impacts the ADR. RESULTS: A total of 1142 subjects (age, 62.3 ± 8.9 years; 80.5% men) underwent screening (45.9%) or surveillance (53.6%) colonoscopy. The screening group had a median withdrawal time of 9.0 minutes (interquartile range [IQR], 3.3) with an ADR of 49.6%, whereas the surveillance group had a median withdrawal time of 9.3 minutes (IQR, 4.3) with an ADR of 63.9%. ADR correspondingly increased for a withdrawal time of 6 minutes to 13 minutes, beyond which ADR did not increase (50.4% vs 76.6%, P < .01). For every 1-minute increase in withdrawal time, there was 6% higher odds of detecting an additional subject with an adenoma (OR, 1.06; 95% confidence interval, 1.02-1.10; P = .004). CONCLUSIONS: Results from this multicenter, randomized controlled trial underscore the importance of a high-quality examination and efforts required to achieve this with an incremental yield in ADR based on withdrawal time. (Clinical trial registration number: NCT03952611.).

Diagnostic performance of volumetric laser endomicroscopy for Barrett's esophagus dysplasia amongst gastroenterology trainees.

BACKGROUND: Volumetric laser endomicroscopy (VLE) is an advanced imaging modality used in Barrett's esophagus (BE) surveillance. VLE image interpretation is challenged by subtle grayscale image variation across a large amount of data. Training in VLE interpretation is not standardized. This study aims to determine if VLE training can be incorporated into a gastroenterology (GI) fellowship curriculum with the use of a self-directed module. METHODS: A standardized, self-directed training module (30 min) was created explaining the background and established VLE criteria for the diagnosis of BE dysplasia. A VLE image dataset was generated from a multicenter VLE database of targeted biopsies. GI trainees were asked to grade each image for the presence or absence of the following criteria (I) increased surface optical frequency domain imaging (OFDI) signal intensity and (II) atypical glands and provide a final diagnosis (dysplastic vs. non-dysplastic). Diagnostic performance was calculated and results compared to VLE expert interpretation using histology as the gold-standard. RESULTS: The dataset included 50 VLE images (10 high-grade dysplasia, 40 non-dysplastic BE). VLE images were reviewed in a randomized and blinded fashion by 5 GI trainees with no prior VLE experience and 5 experienced VLE users. Sensitivity, specificity and accuracy of GI trainees was 83.3% (95% CI: 71.5-91.7%), 59.0% (95% CI: 51.6-66.0%), and 64.8% (95% CI: 58.5-70.7%) compared to 80.0% (95% CI: 67.7-89.2%), 79.5% (95% CI: 73.0-85.0%), and 79.6% (95% CI: 74.1-84.4%) for VLE experts respectively. The difference in specificity and accuracy between the two groups were statistically significant with P<0.001. CONCLUSIONS: A brief training session on VLE is inadequate to reach competency in interpretation of VLE by GI trainees. Additional experience is required to accurately interpret VLE images.

High-Definition Colonoscopy Compared With Cuff- and Cap-Assisted Colonoscopy: Results From a Multicenter, Prospective, Randomized Controlled Trial.

BACKGROUND AND AIMS: Mucosal exposure devices including distal attachments such as the cuff and cap have shown variable results in improving adenoma detection rate (ADR) compared with high-definition white light colonoscopy (HDWLE). METHODS: We performed a prospective, multicenter randomized controlled trial in patients undergoing screening or surveillance colonoscopy comparing HDWLE to 2 different types of distal attachments: cuff (CF) (Endocuff Vision) or cap (CP) (Reveal). The primary outcome was ADR. Secondary outcomes included adenomas per colonoscopy, advanced adenoma and sessile serrated lesion detection rate, right-sided ADR, withdrawal time, and adverse events. Continuous variables were compared using Student's t test and categorical variables were compared using chi-square or Fisher's exact test using statistical software Stata version16. A P value <.05 was considered significant. RESULTS: A total of 1203 subjects were randomized to either HDWLE (n = 384; mean 62 years of age; 81.3% males), CF (n = 379; mean 62.7 years of age; 79.9% males) or CP (n = 379; mean age 62.1 years of age; 80.5% males). No significant differences were found among 3 groups for ADR (57.3%, 59.1%, and 55.7%; P = .6), adenomas per colonoscopy (1.4 ± 1.9, 1.6 ± 2.4, and 1.4 ± 2; P = .3), advanced adenoma (7.6%, 9.2%, and 8.2%; P = .7), sessile serrated lesion (6.8%, 6.3%, and 5.5%; P = .8), or right ADR (48.2%, 49.3%, and 46.2%; P = .7). The number of polyps per colonoscopy were significantly higher in the CF group compared with HDWLE and CP group (2.7 ± 3.4, 2.3 ± 2.5, and 2.2 ± 2.3; P = .013). In a multivariable model, after adjusting for age, sex, body mass index, withdrawal time, and Boston Bowel Preparation Scale score, there was no impact of device type on the primary outcome of ADR (P = .77). In screening patients, CF resulted in more neoplasms per colonoscopy (CF: 1.7 ± 2.6, HDWLE: 1.3 ± 1.7, and CP: 1.2 ± 1.8; P = .047) with a shorter withdrawal time. CONCLUSIONS: Results from this multicenter randomized controlled trial do not show any significant benefit of using either distal attachment devices (CF or CP) over HDWLE, at least in high-detector endoscopists. The Endocuff may have an advantage in the screening population. (ClinicalTrials.gov, Number: NCT03952611).

Diagnostic accuracy of a novel third generation esophageal capsule as a non-invasive detection method for Barrett's esophagus: A pilot study.

BACKGROUND AND AIM: Previous two generations of esophageal capsule did not show adequate detection rates for Barrett's esophagus (BE). We assessed the diagnostic accuracy of a novel third generation capsule with an improved frame rate of 35 frames per second for the detection of BE in a pilot study. METHODS: This was a blinded prospective pilot study conducted at a tertiary medical center. Patients with known BE (at least C0M > 1) who presented for endoscopic surveillance (May to October 2017) were included. All patients underwent novel esophageal capsule (PillCam™ UGI; Medtronic) ingestion using the simplified ingestion protocol followed by standard high-definition upper endoscopy (esophagogastroduodenoscopy [EGD]). Capsule endoscopy findings were interpreted by examiners blinded to endoscopy results and compared with endoscopic findings (gold standard). Following completion of both tests, a subjective questionnaire was provided to all patients regarding their experience. RESULTS: Twenty patients (95%males, mean age 66.3 [±7.9] years) with BE undergoing surveillance EGD were eligible. The mean BE length was 3.5 (±2.7) cm. Novel esophageal capsule detected BE in 75% patients when images were compared with endoscopy. Novel capsule detected BE in 82% patients when the BE length was ≥2 cm. The mean esophageal transit time was 0.59 s. On a subjective questionnaire, all 20 patients reported novel capsule as being more convenient compared with EGD. CONCLUSIONS: In this pilot, single-center study, novel esophageal capsule was shown to be not ready for population screening of BE. Studies integrating artificial intelligence into improved quality novel esophageal capsule should be performed for BE screening.

Efficacy and safety of over-the-scope clips for gastrointestinal bleeding: a systematic review and meta-analysis.

BACKGROUND: The over-the-scope clip (OTSC) has been increasingly utilized for the management of gastrointestinal (GI) bleeding. Limited efficacy data are currently available from large-scale studies. METHODS: An electronic database search was conducted for eligible articles using OTSCs for hemostasis in GI bleeding. The primary outcome was the rate of definitive hemostasis after primary hemostasis and without rebleeding at follow-up. Secondary outcomes were: primary technical success, primary clinical success, rebleeding, and failure rates. Pooled rates were expressed as proportions of patients with events over total patients, 95 % confidence limits (CI) with heterogeneity, and P values of < 0.05 for significance. RESULTS: A total of 21 studies (n = 851) were analyzed (62.2 % males), with a median patient age of 69.7 years. The definitive hemostasis rate was 87.8 % (95 %CI 83.7 % - 92 %) after a median follow-up of 56 days. The OTSC was successfully deployed in 97.8 % of patients (95 %CI 96.7 % - 98.9 %) and the primary clinical success rate was 96.6 % (95 %CI 95.1 % - 98.2 %). Rebleeding was seen in 10.3 % of patients (95 %CI 6.5 % - 14.1 %). The failure rate of OTSCs was 9 % (95 %CI 5.2 % - 12.8 %) when used as first-line treatment and 26 % (95 %CI 16.1 % - 36.0 %) when used as second-line treatment. CONCLUSION: This systematic review showed high rates of definitive hemostasis, technical success, and clinical success, along with low rebleeding rates when OTSCs were used for the treatment of GI bleeding. The lack of randomized controlled trials of OTSC vs. other therapies makes comparison with conventional treatment difficult.

Improving serrated adenoma detection rate in the colon by electronic chromoendoscopy and distal attachment: systematic review and meta-analysis.

BACKGROUND AND AIMS: The evidence for modification of conventional colonoscopy using either "distal attachments" (DAs; endocap, endocuff, and endoring) or "electronic chromoendoscopy" (EC; narrow-band imaging [NBI], iScan, blue-light imaging, autofluorescence imaging, and linked-color imaging) to improve the detection of serrated adenomas during colonoscopy has shown conflicting results. METHODS: A comprehensive literature search was performed using Medline, Google Scholar, Embase, and Cochrane Library based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized controlled trials (RCTs) comparing any DA or EC with high-definition white-light colonoscopy for detection of serrated adenomas (sessile serrated adenoma/polyp and traditional serrated adenoma) were included. The primary outcome was serrated adenoma detection rate (SADR) defined as the number of patients with at least 1 serrated adenoma of total patients in that group. The secondary outcome was the number of serrated adenomas per subject. Pooled rates were reported using risk ratio (RR) with 95% confidence interval. RESULTS: Seventeen studies with 13,631 patients (56% men; age range, 50-66 years) met the inclusion criteria. The use of DAs (RR, 1.21; P = .45) and EC (RR, 1.29; P = .09) during colonoscopy did not show a significant improvement in SADR. The SADR using EC was 6.9% (4 studies) and that with NBI alone was 3.7% (3 studies). CONCLUSIONS: The results indicate that, except for NBI, the use of DAs or EC during colonoscopy does not improve detection of serrated adenomas in the colon. More RCTs evaluating NBI are needed to explore the effect.

Hot snare vs. cold snare polypectomy for endoscopic removal of 4 - 10 mm colorectal polyps during colonoscopy: a systematic review and meta-analysis of randomized controlled studies.

Introduction In recent years, cold snare polypectomy (CSP) has increasingly been used over hot snare polypectomy (HSP) for the removal of colorectal polyps (4 - 10 mm in size). However, the optimal technique (CSP vs. HSP), in terms of complete polyp resection and complications, is uncertain. Our aim was to compare incomplete resection rate (IRR) of polyps and complications using CSP vs. HSP. Methods Randomized controlled studies (RCTs) comparing CSP and HSP for removal of 4 - 10 mm colorectal polyps were considered. Studies were included in the analysis if they obtained biopsy specimens from the resection margin to confirm the absence of residual tissue and reported complications. IRR and complication rate were the outcome measures. Pooled rates were reported as Odds Ratios (OR) or risk difference with 95 % Confidence Interval (CI). Results In total, three RCTs were included in the final analysis. A total of 1051 patients with 1485 polyps were randomized to either HSP group (n = 741 polyps) or CSP group (n = 744 polyps). The overall IRR did not differ between the two groups (HSP vs. CSP: 2.4 % vs. 4.7 %; OR 0.51, 95 %CI 0.13 - 1.99, P  = 0.33, I 2  = 73 %). The HSP group had a lower rate of overall complications compared to the CSP group (3.7 % vs. 6.6 %; OR 0.53, 95 % CI 0.3 - 0.94, P  = 0.03, I 2  = 0 %). Polyp retrieval rates were not different between the two groups (99 % vs. 98.1 %). Conclusion Our results suggest that HSP and CSP techniques can be effectively used for the complete removal of 4 - 10 mm colorectal polyps; however, HSP has a lower incidence of overall complications.

Significantly lower annual rates of neoplastic progression in short- compared to long-segment non-dysplastic Barrett's esophagus: a systematic review and meta-analysis.

BACKGROUND: Although shorter lengths of Barrett's esophagus (BE) have been associated with a lower risk of neoplastic progression, precise estimates have varied, especially for non-dysplastic BE (NDBE) only. Therefore, current US guidelines do not provide specific recommendations on surveillance intervals based on BE length. We performed a systematic review and meta-analysis of the published literature to examine neoplastic progression rates of NDBE based on BE length. METHODS: PubMed, Cochrane, Google Scholar, and Embase were comprehensively searched. Studies reporting progression rates in patients with NDBE and > 1 year of follow-up were included. The number of patients progressing to esophageal adenocarcinoma (EAC) and high grade dysplasia (HGD)/EAC in individual studies and the mean follow-up were recorded to derive person-years of follow-up. Pooled rates of progression to EAC and HGD/EAC based on BE length (< 3 cm vs. ≥ 3 cm) were calculated. RESULTS: Of the 486 initial studies identified, 10 met the inclusion/exclusion criteria. These included a total of 4097 NDBE patients; 1979 with short-segment BE (SSBE; 10 773 person-years of follow-up) and 2118 with long-segment BE (LSBE; 12 868 person-years). The annual rates of progression to EAC were significantly lower for SSBE compared with LSBE: 0.06 % (95 % confidence interval 0.01 % - 0.10 %) vs. 0.31 % (0.21 % - 0.40 %), respectively; odds ratio (OR) 0.25 (0.11 - 0.56); P < 0.001, as were the rates for the combined endpoint (HGD/EAC): 0.24 % (0.09 % - 0.32 %) vs. 0.76 % (0.43 % - 0.89 %), respectively; OR 0.35 (0.21 - 0.58); P < 0.001. There was no significant heterogeneity among studies. CONCLUSION: The results demonstrate significantly lower rates of neoplastic progression in NDBE patients with SSBE compared with LSBE. BE length can easily be used for risk stratification purposes for NDBE patients undergoing surveillance endoscopy and consideration should be given to tailoring surveillance intervals based on BE length in future US guidelines.

Characterising N-acetylglucosaminylphosphatidylinositol de-N-acetylase (CaGpi12), the enzyme that catalyses the second step of GPI biosynthesis in Candida albicans.

Candida albicans N-acetylglucosaminylphosphatidylinositol de-N-acetylase (CaGpi12) recognises N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI) from Saccharomyces cerevisiae and is able to complement ScGPI12 function. Both N- and C-terminal ends of CaGpi12 are important for its function. CaGpi12 was biochemically characterised using rough endoplasmic reticulum microsomes prepared from BWP17 strain of C. albicans. CaGpi12 is optimally active at 30°C and pH 7.5. It is a metal-dependent enzyme that is stimulated by divalent cations but shows no preference for Zn2+ unlike the mammalian homologue. It irreversibly loses activity upon incubation with a metal chelator. Two conserved motifs, HPDDE and HXXH, are both important for its function in the cell. CaGPI12 is essential for growth and viability of C. albicans. Its loss causes reduction of GlcNAc-PI de-N-acetylase activity, cell wall defects and filamentation defects. The filamentation defects could be specifically correlated to an upregulation of the HOG1 pathway.

Validation of Probe-based Confocal Laser Endomicroscopy (pCLE) Criteria for Diagnosing Colon Polyp Histology.

BACKGROUND: Validated probe-based confocal endomicroscopy (pCLE) criteria for distinguishing hyperplastic polyps (HPs) and tubular adenomas (TA) have not yet been developed. AIM: To develop pCLE criteria for distinguishing HP from TA and evaluate its performance characteristics among experts. METHODS: pCLE criteria for colon polyp histology were developed and tested in 2 phases prospectively. Phase I: 8 preliminary criteria were developed and tested internally. Criteria achieving an accuracy of >75% (epithelial surface: regular vs. irregular; goblet cells: increased vs. decreased; gland axis: horizontal vs. vertical; gland shape: slit/stellate vs. villiform; image scale: gray vs. dark) were evaluated in Phase II of study wherein external assessors evaluated these criteria in a separate set of pCLE videos. Accuracy and interobserver agreement (95% confidence intervals) were determined for colon histology prediction. RESULTS: Phase I (criteria development/internal testing): 8 criteria were assessed by 4 pCLE experts using 28 videos (14 HP/14 TA). Five of 8 pCLE criteria met selection for phase II (accuracy >75%). Phase II (external validation): 36 pCLE colon polyp videos (HP 16/TA 20) were evaluated by 8 external assessors. Overall accuracy in diagnosis of colon polyp histology was 84.9% (95% confidence interval, 81.7-87.7). Of predictions made with high confidence (75%), histology was predicted with an accuracy of 91%, sensitivity 83%, specificity 100%, negative predictive value 87% and positive predictive value 98%. Interobserver agreement was substantial (κ=0.73). CONCLUSIONS: We demonstrate the development and validation of pCLE criteria for prediction of colon polyp histology. Using these criteria, overall accuracy in differentiating TA from HP was high with substantial interobserver agreement.

Short-Term Clinical Response to Corticosteroids Can Predict Long-Term Natural History of Ulcerative Colitis: Prospective Study Experience.

BACKGROUND: Long-term outcome and natural history of steroid response in adult ulcerative colitis patients based on short-term response is largely unknown. AIM: To evaluate whether short-term clinical response at 30  days after steroid initiation for moderate to severe disease can predict long-term outcome. METHODS: This prospective observational study recruited 161 patients who received oral/intravenous steroid therapy at our institution from April 2005 to July 2009. Short-term response at 30 days and long-term response at the end of first and third years were measured. Risk factors for long-term outcome at 1 and 3 years were analyzed by multivariate regression model. RESULTS: At the end of 30 days, 90 patients (55.9%) had complete response, 47 (29.2%) partial response, and 24 (14.9%) did not respond at all. At the end of first year, 53/90 (60%) complete responders (at 30 days) maintained steroid-free remission when compared to 17/71 (23.9%, p < 0.001) partial/no responders. Similar result was observed at the end of third year (74.7 vs 55.1%, p = 0.017). On multivariable analysis, short-term outcome at 30 days was a predictor of outcome at the end of one year (RR 4.1, 95% CI 2.2-8.5) and 3 years (RR 2.1, 95% CI 1.02-4.5). CONCLUSIONS: Short-term response to steroids is a strong predictor of long-term outcome at 1 and 3 years in active ulcerative colitis patients.

Normal saline solution versus other viscous solutions for submucosal injection during endoscopic mucosal resection: a systematic review and meta-analysis.

BACKGROUND AND AIMS: EMR is being increasingly practiced for the removal of large colorectal polyps. A variety of solutions such as normal saline solution (NS) and other viscous and hypertonic solutions (VS) have been used as submucosal injections for EMR. A systematic review and meta-analysis is presented comparing the efficacy and adverse events of EMR performed using NS versus VS. METHODS: Two independent reviewers conducted a search of all databases for human, randomized controlled trials that compared NS with VS for EMR of colorectal polyps. Data on complete en bloc resection, presence of residual lesions, and adverse events were extracted using a standardized protocol. Pooled odds ratio (OR) estimates along with 95% confidence intervals (CI) were calculated using fixed effect or random effects models. RESULTS: Five prospective, randomized controlled trials (504 patients) met the inclusion criteria. The mean polyp sizes were 20.84 mm with NS and 21.44 mm with VS. On pooled analysis, a significant increase in en bloc resection (OR, 1.91; 95% CI, 1.11-3.29; P = .02; I2 = 0%) and decrease in residual lesions (OR, 0.54; 95% CI, 0.32-0.91; P = .02; I2 = 0%) were noted in VS compared with NS. There was no significant difference in the rate of overall adverse events between the 2 groups. CONCLUSIONS: Use of VS during EMR leads to higher rates of en bloc resection and lower rates of residual lesions compared with NS, without any significant difference in adverse events. Endoscopists could consider using VS for EMR of large colorectal polyps and NS for smaller polyps because there is no significant difference in the outcomes with lesions <2 cm.

Primary sclerosing cholangitis and the risk of colon neoplasia in patients with Crohn's colitis.

BACKGROUND AND AIM: Crohn's colitis (CC) is associated with primary sclerosing cholangitis (PSC). However the risk of colon cancer or dysplasia in CC and PSC is unclear. Our aim was to study the risk of colon neoplasia in CC in patients with and without PSC. METHODS: This is a nested, case-control cohort study of all patients diagnosed with concurrent CC and PSC, seen at the Cleveland Clinic between 1985 and 2012. Forty-three patients with both CC and PSC were compared with a random sample of 159 CC controls without PSC during the same period. RESULTS: Seven (16.3%) of 43 CC patients with PSC developed colon cancer or dysplasia, compared with 22 (13.8%) of 159 controls (P = 0.98). Of seven colon neoplasia cases in the PSC group, 100% occurred proximal to the splenic flexure, compared with 50% (11/22) cases of colon neoplasia in controls occurring in the proximal colon (P = 0.001). Based on Cox regression analysis, male gender independently increased the risk of neoplasia [hazard ratio (HR) = 2.68; 95% confidence interval (CI) 1.30-5.54; P = 0.008], as did age at CC diagnosis (HR = 1.29; 95% CI 1.14-1.47; P < 0.001), while the use of azathioprine/6-mercaptopurine was protective (HR = 0.30; 95% CI 0.13-0.70; P = 0.005). The presence of PSC did not increase the risk for colon neoplasia (HR = 0.45; 95% CI 0.18-1.13; P = 0.09). CONCLUSIONS: CC patients with PSC appear not to be at increased risk of developing colon neoplasia. Among patients in our cohort with colon neoplasia and concurrent PSC, the neoplasia occurred in the proximal colon in all cases.

Effect of quality of bowel preparation on quality indicators of adenoma detection rates and colonoscopy completion rates.

BACKGROUND AND AIM: Adequate bowel preparation is important for safe and effective colonoscopy. Quality indicators (QI) for colonoscopy include achieving at least 95% completion rate and an adenoma detection rate (ADR) of at least 25% in average-risk men and 15% in average-risk women aged over 50. Our aim was to investigate the impact of bowel preparation on ADR and colonoscopy completion rates. METHODS: This retrospective cohort study included patients who underwent colonoscopy between January 2008 and December 2009. The main outcome measurements were ADR and colonoscopy completion rates to the cecum. RESULTS: A total of 2519 patients was included; 1030 (41.0%) had excellent preparation, 1145 (45.5%) good-, 240 (9.5%) fair-, and 104 (4.1%) poor preparation. Colonoscopy completion rates were significantly lower in patients with poor or fair preparation (72.1% and 75.4%, respectively) than in those with good and excellent preparation (99.7% and 99.9%, respectively; P < 0.001), and significantly lower than the QI of 95% (P < 0.001). ADR in men and women combined was similar in all four grades of preparation (excellent, good, fair and poor) at 24.2% vs. 26.8% vs. 32.1% vs. 22.1%, respectively; P = 0.06. All the groups had ADR above the QI (25% for men and 15% for women) with evidence of significantly higher ADR in the women with excellent or good preparation and in men with excellent, good or fair preparation. On multivariate analysis, male gender was significantly associated with increased ADR (P < 0.001), while the quality of bowel preparation did not influence ADR. CONCLUSIONS: Patients with fair and poor standards of preparation have significantly lower colonoscopy completion rates than those with excellent and good preparation. However, there was no difference in ADR between the different grades of preparation.

Adenoma detection rate in high-risk patients differs from that in average-risk patients.

BACKGROUND: Adenoma detection rates (ADRs) are established as quality targets in average-risk (AR) individuals undergoing colorectal cancer (CRC) screening colonoscopy. Little is known about the ADR in high-risk (HR) individuals undergoing index or surveillance colonoscopy. OBJECTIVE: To determine and compare ADR in HR versus AR individuals undergoing colonoscopy. DESIGN AND SETTING: Retrospective study, tertiary care center. PATIENTS AND INTERVENTION: We reviewed records of 7357 patients who underwent colonoscopy by 66 multispecialty endoscopists at our institution during the period 2008 to 2009. Both screening and surveillance colonoscopies in AR and HR patients for CRC were studied. HR patients were further divided into 3 subgroups: those with a (1) personal history of polyps (PHP), (2) family history of polyps (FHP), and (3) family history of CRC (FHCRC). Multivariable logistic regression analysis was performed to evaluate differences in ADR between the groups after adjusting for possible confounders. MAIN OUTCOME MEASUREMENTS: ADR in HR patients. RESULTS: The study included 4141 patients, of whom 2170 were AR and 1971 were HR. Patients in the HR group were older (64.5 ± 9.1 years vs 59.1 ± 7.9 years, P < .001). HR patients were more likely to have adenomas (30.7% vs 25.6%, P < .001). Adenomas were detected more often in the proximal colon than in the distal colon (29.3% vs 21.0%, P < .001 and 22.8% vs 15.8%, P < .001, respectively). Patients with a PHP had the highest ADR (33.1%, P < .001). However, after adjusting for confounders, HR status was not found to be associated with ADR (odds ratio [OR] 1.2; 95% confidence interval [CI], 0.93-1.6; P = .15 for females and 0.93; 95% CI, 0.70-1.2; P = .61 for males). HR females were found to have a 40% greater likelihood of having proximal adenomas than AR females (1.4; 95% CI, 1.01-2; P = .04). LIMITATIONS: Retrospective design, single tertiary center. CONCLUSIONS: Patients with a PHP have a significantly higher ADR compared with AR patients. Defining a minimum target ADR for individuals with a PHP undergoing surveillance colonoscopy is important.

VSL#3 induces and maintains short-term clinical response in patients with active microscopic colitis: a two-phase randomised clinical trial.

BACKGROUND: The probiotic mixture VSL#3 has proven efficacious in inflammatory bowel diseases and irritable bowel syndrome; however, its efficacy in microscopic colitis (MC) is being investigated. OBJECTIVE: To evaluate the safety and efficacy of a multistrain probiotic, VSL#3, in inducing clinical remission and achieving clinical response, as compared with mesalamine, in patients with active MC. METHODS: A randomised, open labelled study comparing the efficacy of 900 billion colony-forming units/day of VSL#3 (group (Gp) A) or 1.6 g of mesalamine/day (Gp B) for 8 weeks in 30 patients with MC was conducted. After a washout period of 2 weeks, Gp B received 8 weeks of VSL#3 and Gp A was off medication for the next 8 weeks. The primary end points were clinical remission and clinical response at 8 weeks. RESULTS: Of 30 patients, 15 were randomised in each arm. 11 patients in Gp A and 13 patients in Gp B completed 8 weeks of treatment. 5 (46%) of 11 patients in Gp A and 1 (8%) of 13 patients in Gp B attained clinical remission (p=0.022). Clinical response was seen in Gp A, as evidenced by a lower stool weight (377.6±104.5 g) as compared with Gp B (507±168.2 g; p=0.03). VSL#3 was effective in maintaining clinical response up to 10 weeks, even after discontinuation of therapy. Secondary end points like stool parameters, histology and well-being improved in both treatment groups. CONCLUSIONS: The probiotic VSL#3 was found to offer the benefit of inducing as well as maintaining short-term clinical response in patients with active MC. TRIAL REGISTRATION NUMBER: The clinical trial is registered with CLINICAL TRIAL REGISTRY INDIA; http://ctri.nic.in, CTRI No. "CTRI/2008/091/000086" (registered on: 23/06/2008).

Frequency and risk factors of low immunoglobulin levels in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) are considered to be dysregulated, immune-mediated disorders; and immunosuppressive medications are the mainstay of their treatment. Clinically, we have often observed low serum immunoglobulin (Ig) levels in these patients. The aim of this study was to assess the frequency and risk factors of secondary humoral immunodeficiency in IBD patients. METHODS: We conducted a cross-sectional study of eligible IBD patients with Crohn's disease (CD), ulcerative colitis (UC), indeterminate colitis (IC) or restorative proctocolectomy with ileal pouch, who having serum Ig measured. Demographic and clinical variables were measured. Univariate and multivariate analyses were performed. RESULTS: A total of 324 patients was included, with a mean age of 38.8 years and 158 (48.8%) being male. Low IgG, IgG1, IgA, and IgM were found in 22.7%, 23.4%, 7.9%, and 10.9% of patients, respectively. The shared risk factors for a low IgG or IgM level were increasing age [odds ratio (OR) = 1.13; 95% confidence interval (CI) 1.03-1.23 for low IgG level and OR = 1.33; 95% CI 1.15-1.56 for low IgM level] and hypoalbuminemia (OR = 1.83; 95% CI 1.01-3.33 for low IgG level and OR = 3.17; 95% CI 1.23-8.15 for low IgM level). In addition, thioprine use was associated with low IgA level (OR = 2.76; 95% CI 1.03-7.39). IBD disease duration was a risk factor for low IgG1 level (OR = 1.40; 95% CI 1.12-1.76). The presence of concurrent primary sclerosing cholangitis (OR = 0.064; 95% CI 0.007-0.60) and the use of biologics (OR = 0.16; 95% CI 0.033-0.79) were associated with normal IgG1 level. IgG level was lower in CD patients than that in UC/IC and ileal pouch patients (P = 0.042). IgG and IgA levels were elevated in patients with inflammatory conditions of the pouch (P = 0.01; P = 0.003, respectively). CONCLUSIONS: Low Ig level appears to be common in IBD patients. Increasing age, disease duration and hypoalbuminemia appeared to be risk factors. The findings may provide rationale for targeted therapy to boost humoral immunity in selected patients with IBD.

Emergency department visits related to cirrhosis: a retrospective study of the nationwide emergency department sample 2006 to 2011.

There is scant literature about cirrhosis and its associated complications in a non-hospitalized population.To study the epidemiology of cirrhosis-associated Emergency Department visits in the US.Estimates were calculated in patients' ≥18 years using the Nationwide Emergency Department Sample.The number of visits associated with an International Classification of Diseases-9 diagnosis code of cirrhosis increased non-significantly from 23.81/10,000 population (2006) to 23.9/10,000 population (2011; P = 0.05). A majority of these patients (75.30%) underwent hospital admission, the greatest risk factor for this was the presence of ≥3 comorbidities (adjusted odds ratio 30.8; 95% Confidence Interval 30.4-31.2). Infection was the most frequent concurrent complicating diagnosis associated with cirrhosis (20.1%). There was a decreased incidence in most of the complicating conditions except for hepatorenal syndrome and spontaneous bacterial peritonitis.Our results indicate a stable trend for cirrhosis-associated Emergency Department visits from 2006 to 2011. Further studies are required to investigate the increased incidence of spontaneous bacterial peritonitis and hepatorenal renal syndrome in the cirrhotic population.

Induction with NCB-02 (curcumin) enema for mild-to-moderate distal ulcerative colitis - a randomized, placebo-controlled, pilot study.

BACKGROUND AND AIMS: Curcumin, an active ingredient of turmeric with anti-inflammatory properties, has been demonstrated to be useful in experimental models of ulcerative colitis (UC). It's efficacy in humans needs to be investigated. METHODS: A randomized, double-blind, single-centre pilot trial was conducted in patients with distal UC (<25 cm involvement) and mild-to-moderate disease activity. Forty-five patients were randomized to either NCB-02 (standardized curcumin preparation) enema plus oral 5-ASA or placebo enema plus oral 5-ASA. Primary end point was disease response, defined as reduction in Ulcerative Colitis Diseases Activity Index by 3 points at 8 weeks, and secondary end points were improvement in endoscopic activity and disease remission at 8 weeks. RESULTS: Response to treatment was observed in 56.5% in NCB-02 group compared to 36.4% (p=0.175) in placebo group. At week 8, clinical remission was observed in 43.4% of patients in NCB-02 group compared to 22.7% in placebo group (p=0.14) and improvement on endoscopy in 52.2% of patients in NCB-02 group compared to 36.4% of patients in placebo group (p=0.29). Per protocol analysis revealed significantly better outcomes in NCB-02 group, in terms of clinical response (92.9% vs. 50%, p=0.01), clinical remission (71.4% vs. 31.3%, p=0.03), and improvement on endoscopy (85.7% vs. 50%, p=0.04). CONCLUSION: In this pilot study we found some evidence that use of NCB-02 enema may tend to result in greater improvements in disease activity compared to placebo in patients with mild-to-moderate distal UC. The role of NCB-02 as a novel therapy for UC should be investigated further.