Screening uptake of colonoscopy versus fecal immunochemical testing in first-degree relatives of patients with non-syndromic colorectal cancer: A multicenter, open-label, parallel-group, randomized trial (ParCoFit study).

BACKGROUND: Colonoscopy screening is underused by first-degree relatives (FDRs) of patients with non-syndromic colorectal cancer (CRC) with screening completion rates below 50%. Studies conducted in FDR referred for screening suggest that fecal immunochemical testing (FIT) was not inferior to colonoscopy in terms of diagnostic yield and tumor staging, but screening uptake of FIT has not yet been tested in this population. In this study, we investigated whether the uptake of FIT screening is superior to the uptake of colonoscopy screening in the familial-risk population, with an equivalent effect on CRC detection. METHODS AND FINDINGS: This open-label, parallel-group, randomized trial was conducted in 12 Spanish centers between February 2016 and December 2021. Eligible individuals included asymptomatic FDR of index cases <60 years, siblings or ≥2 FDR with CRC. The primary outcome was to compare screening uptake between colonoscopy and FIT. The secondary outcome was to determine the efficacy of each strategy to detect advanced colorectal neoplasia (adenoma or serrated polyps ≥10 mm, polyps with tubulovillous architecture, high-grade dysplasia, and/or CRC). Screening-naïve FDR were randomized (1:1) to one-time colonoscopy versus annual FIT during 3 consecutive years followed by a work-up colonoscopy in the case of a positive test. Randomization was performed before signing the informed consent using computer-generated allocation algorithm based on stratified block randomization. Multivariable regression analysis was performed by intention-to-screen. On December 31, 2019, when 81% of the estimated sample size was reached, the trial was terminated prematurely after an interim analysis for futility. Study outcomes were further analyzed through 2-year follow-up. The main limitation of this study was the impossibility of collecting information on eligible individuals who declined to participate. A total of 1,790 FDR of 460 index cases were evaluated for inclusion, of whom 870 were assigned to undergo one-time colonoscopy (n = 431) or FIT (n = 439). Of them, 383 (44.0%) attended the appointment and signed the informed consent: 147/431 (34.1%) FDR received colonoscopy-based screening and 158/439 (35.9%) underwent FIT-based screening (odds ratio [OR] 1.08; 95% confidence intervals [CI] [0.82, 1.44], p = 0.564). The detection rate of advanced colorectal neoplasia was significantly higher in the colonoscopy group than in the FIT group (OR 3.64, 95% CI [1.55, 8.53], p = 0.003). Study outcomes did not change throughout follow-up. CONCLUSIONS: In this study, compared to colonoscopy, FIT screening did not improve screening uptake by individuals at high risk of CRC, resulting in less detection of advanced colorectal neoplasia. Further studies are needed to assess how screening uptake could be improved in this high-risk group, including by inclusion in population-based screening programs. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT02567045).

Quality of Colonoscopy Is Associated With Adenoma Detection and Postcolonoscopy Colorectal Cancer Prevention in Lynch Syndrome.

BACKGROUND & AIMS: Colonoscopy reduces colorectal cancer (CRC) incidence and mortality in Lynch syndrome (LS) carriers. However, a high incidence of postcolonoscopy CRC (PCCRC) has been reported. Colonoscopy is highly dependent on endoscopist skill and is subject to quality variability. We aimed to evaluate the impact of key colonoscopy quality indicators on adenoma detection and prevention of PCCRC in LS. METHODS: We conducted a multicenter study focused on LS carriers without previous CRC undergoing colonoscopy surveillance (n = 893). Incident colorectal neoplasia during surveillance and quality indicators of all colonoscopies were analyzed. We performed an emulated target trial comparing the results from the first and second surveillance colonoscopies to assess the effect of colonoscopy quality indicators on adenoma detection and PCCRC incidence. Risk analyses were conducted using a multivariable logistic regression model. RESULTS: The 10-year cumulative incidence of adenoma and PCCRC was 60.6% (95% CI, 55.5%-65.2%) and 7.9% (95% CI, 5.2%-10.6%), respectively. Adequate bowel preparation (odds ratio [OR], 2.07; 95% CI, 1.06-4.3), complete colonoscopies (20% vs 0%; P = .01), and pan-chromoendoscopy use (OR, 2.14; 95% CI, 1.15-3.95) were associated with significant improvement in adenoma detection. PCCRC risk was significantly lower when colonoscopies were performed during a time interval of less than every 3 years (OR, 0.35; 95% CI, 0.14-0.97). We observed a consistent but not significant reduction in PCCRC risk for a previous complete examination (OR, 0.16; 95% CI, 0.03-1.28), adequate bowel preparation (OR, 0.64; 95% CI, 0.17-3.24), or previous use of high-definition colonoscopy (OR, 0.37; 95% CI, 0.02-2.33). CONCLUSIONS: Complete colonoscopies with adequate bowel preparation and chromoendoscopy use are associated with improved adenoma detection, while surveillance intervals of less than 3 years are associated with a reduction of PCCRC incidence. In LS, high-quality colonoscopy surveillance is of utmost importance for CRC prevention.

Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study.

BACKGROUND: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed. OBJECTIVE: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergies. METHODS: The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization from Canadian (n = 150) and Austrian (n = 50) tertiary pediatric centers. BAT using %CD63+ basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000 ng/mL protein). BAT results were assessed against confirmed allergic status in a blinded fashion to develop a generalizable statistical model for comparison to extract and marker allergen-specific IgE. RESULTS: A mixed effect model integrating BAT results for 10 and 100 ng/mL of peanut and individual tree nut extracts was optimal. The area under the ROC curve (AUROC) was 0.98 for peanut, 0.97 for cashew, 0.92 for hazelnut, 0.95 for pistachio, and 0.97 for walnut. The BAT outperformed sIgE testing for peanut or hazelnut and was comparable for walnut (AUROC 0.95, 0.94, 0.92) in a sub-analysis in sensitized patients undergoing OFC. CONCLUSIONS: Basophil activation test can predict allergic clinical status to peanut and tree nuts in multi-nut-sensitized children and may reduce the need for high-risk OFCs in patients.

Variation in Colonoscopy Performance Measures According to Procedure Indication.

BACKGROUND & AIMS: Most fulfillment and benchmarking information for colonoscopy quality indicators has been obtained from studies of primary screening colonoscopies. We analyzed differences in the fulfillment of colonoscopy quality indicators based on the indication for endoscopy. METHODS: We performed an observational, multicenter, cross-sectional study of 14,867 patients who underwent endoscopy procedures for gastrointestinal symptoms (40.3%), a positive result from a fecal immunochemical test (36.0%), postpolypectomy surveillance (15.3%), or primary screening (8.4%), from February 2016 through December 2017 at 14 centers in Spain. We evaluated rates of adequate colon cleansing, cecal intubation, adenoma detection, and colorectal cancer detection, among others. We used findings from primary screening colonoscopies as the reference standard. RESULTS: Fewer than 90% of patients had adequate bowel preparation; 83.1% of patients with gastrointestinal symptoms had adequate bowel preparation (odds ratio [OR] compared with patients with primary screening colonoscopies, 0.62; 95% CI, 0.49-0.78) and 85.3% of patients receiving postpolypectomy surveillance had adequate bowel preparation (OR, 0.71; 95% CI, 0.55-0.91). The cecal intubation rate was also lower in patients with gastrointestinal symptoms (93.1%) (OR, 0.34; 95% CI, 0.22-0.52). The adenoma detection rate was higher in patients with a positive result from a fecal immunochemical test (46.4%) (OR, 2.01; 95% CI, 1.71-2.35) and in patients undergoing postpolypectomy surveillance (48.2%) (OR, 1.41; 95% CI, 1.20-1.67). The highest proportion of patients with colorectal cancer was in the gastrointestinal symptom group (5.1%) (OR, 5.24; 95% CI, 2.30-11.93) and the lowest was in patients undergoing surveillance (0.8%) (OR, 0.83; 95% CI, 0.32-2.14). CONCLUSIONS: Fulfillment of colonoscopy performance measures varies substantially by indication. Policies addressing performance measures beyond colonoscopy screening procedures should be developed. Benchmarking recommendations could be adjusted according to colonoscopy indication.

Clinical and Pathological Characterization of Lynch-Like Syndrome.

BACKGROUND & AIMS: Lynch syndrome is characterized by DNA mismatch repair (MMR) deficiency. Some patients with suspected Lynch syndrome have DNA MMR deficiencies but no detectable mutations in genes that encode MMR proteins-this is called Lynch-like syndrome (LLS). There is no consensus on management of patients with LLS. We collected data from a large series of patients with LLS to identify clinical and pathology features. METHODS: We collected data from a nationwide-registry of patients with colorectal cancer (CRC) in Spain. We identified patients whose colorectal tumors had loss of MSH2, MSH6, PMS2, or MLH1 (based on immunohistochemistry), without the mutation encoding V600E in BRAF (detected by real-time PCR), and/or no methylation at MLH1 (determined by methylation-specific multiplex ligation-dependent probe amplification), and no pathogenic mutations in MMR genes, BRAF, or EPCAM (determined by DNA sequencing). These patients were considered to have LLS. We collected data on demographic, clinical, and pathology features and family history of neoplasms. The χ2 test was used to analyze the association between qualitative variables, followed by the Fisher exact test and the Student t test or the Mann-Whitney test for quantitative variables. RESULTS: We identified 160 patients with LLS; their mean age at diagnosis of CRC was 55 years and 66 patients were female (41%). The Amsterdam I and II criteria for Lynch syndrome were fulfilled by 11% of cases and the revised Bethesda guideline criteria by 65% of cases. Of the patients with LLS, 24% were identified in universal screening. There were no proportional differences in sex, indication for colonoscopy, immunohistochemistry, pathology findings, or personal history of CRC or other Lynch syndrome-related tumors between patients who met the Amsterdam and/or Bethesda criteria for Lynch syndrome and patients identified in universal screening for Lynch syndrome, without a family history of CRC. CONCLUSIONS: Patients with LLS have homogeneous clinical, demographic, and pathology characteristics, regardless of family history of CRC.

Weedy ferns (Polypodiopsida) in Argentina: diversity, distribution and impact on human activities and ecosystems.

Currently, in Argentina 368 species of true ferns (i.e. Polypodiopsida class) are distributed throughout the country, however, only four of them have been mentioned until now as weeds and ruderal species. The goal of this work was to generate an update of weedy ferns from Argentina, including morphology, distribution, and type of weed according to their impact on natural habitats and/or human activities. All Argentinian fern species were analyzed based on references, herbarium specimens, and field trips. As a result of our study 25 species were recorded from Argentina and classified as segetal, ecological, or aquatic weeds, and ruderal and/or toxic species. Current taxonomic identity, diagnostic characters, origins, habitats, geographical distribution, common names, and impact and potential risks were indicated by species. In addition, we provide a dichotomous key to species, presence of these species in southern South American countries, as well as and photographs in natural habitat. This work represents the first review on native and exotic ferns from Argentina that cause an impact on human activities or disturbe native habitats. The results provide information for the development of weed management tools and priority areas to implement them.

Only α-Gal bound to lipids, but not to proteins, is transported across enterocytes as an IgE-reactive molecule that can induce effector cell activation.

BACKGROUND: The oligosaccharide galactose-α-1,3-galactose (α-Gal), present in mammalian proteins and lipids, causes an unusual delayed allergic reaction 3 to 6 hours after ingestion of mammalian meat in individuals with IgE antibodies against α-Gal. To better understand the delayed onset of allergic symptoms and investigate whether protein-bound or lipid-bound α-Gal causes these symptoms, we analyzed the capacity of α-Gal conjugated proteins and lipids to cross a monolayer of intestinal cells. METHODS: Extracts of proteins and lipids from beef were prepared, subjected to in vitro digestions, and added to Caco-2 cells grown on permeable supports. The presence of α-Gal in the basolateral medium was investigated by immunoblotting, thin-layer chromatography with immunostaining and ELISA, and its allergenic activity was analyzed in a basophil activation test. RESULTS: After addition of beef proteins to the apical side of Caco-2 cells, α-Gal containing peptides were not detected in the basolateral medium. Those peptides that crossed the Caco-2 monolayer did not activate basophils from an α-Gal allergic patient. Instead, when Caco-2 cells were incubated with lipids extracted from beef, α-Gal was detected in the basolateral medium. Furthermore, these α-Gal lipids were able to activate the basophils of an α-Gal allergic patient in a dose-dependent manner. CONCLUSION: Only α-Gal bound to lipids, but not to proteins, is able to cross the intestinal monolayer and trigger an allergic reaction. This suggests that the slower digestion and absorption of lipids might be responsible for the unusual delayed allergic reactions in α-Gal allergic patients and identifies glycolipids as potential allergenic molecules.

Preventive sublingual immunotherapy with House Dust Mite extract modulates epitope diversity in pre-school children.

BACKGROUND: The preventive effect of allergen immunotherapy (AIT) on allergy and asthma development is currently assessed using primary and secondary AIT approaches. Knowledge of the immunological effects of these interventions is limited and the impact on epitope diversity remains to be defined. METHODS: We used high-density peptide arrays that included all known Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f) allergens and the whole proteome of Der f to study changes in House Dust Mite (HDM) linear peptide recognition during a 2-year preventive double-blind placebo-controlled sublingual HDM AIT pilot study in 2-5-year-old children with sensitization to HDM but without symptoms. RESULTS: Preventive AIT-treated patients showed significantly higher IgG epitope diversity to HDM allergens compared to placebo-treated individuals at 24 months of treatment (P < 0.05), while no increase in IgE diversity was seen. At 24 months of treatment, IgG4 diversity for HDM allergens was significantly higher in the pAIT-treated patients compared to placebo group (P < 0.05). Potentially beneficial changes in epitope recognition throughout the treatment are also seen in peptides derived from Der f proteome. CONCLUSION: These data suggest a beneficial immunomodulation of preventive sublingual immunotherapy at a molecular level by favoring a broader blocking repertoire and inhibiting epitope spreading.

"Virtual ileostomy" combined with early endoscopy to avoid a diversion ileostomy in low or ultralow colorectal anastomoses. A preliminary report.

PURPOSE: Despite the benefits of a loop ileostomy after total mesorectal excision (TME), it carries a significant associated morbidity. A "virtual ileostomy" (VI) has been proposed to avoid ileostomies in low-risk patients, which could then be converted into a real ileostomy (RI) in the event of anastomotic leak (AL). The aim of the present study is to evaluate safety and efficacy of VI associated with early endoscopy in patients undergoing rectal surgery with anastomosis to detect subclinical AL prior to the onset of clinical symptoms for sepsis. METHODS: This is a single-center, retrospective study of a consecutive series of patients undergoing elective or emergent colorectal surgery with low or ultralow colorectal or ileorectal anastomosis between September 2015 and September 2016. RESULTS: We included 44 consecutive, unselected patients. Eight patients (18.2%) required conversion into RI and one required terminal colostomy because of AL, of whom 44.4% were asymptomatic and AL was detected with early endoscopy. Fashioning of RI was not associated with further morbidity. All patients with AL converted into RI (n = 8/9) (88.9%), had adequate healed anastomosis, and later underwent stoma closure with no complications. A stoma was avoided in 79.6% of VI. Endoscopy was associated with 55% sensitivity and 100% specificity, with a global accuracy of 88%. CONCLUSIONS: The combination of VI with early postoperative endoscopy could avoid unnecessary ileostomies in patients with low or ultralow anastomoses and reveal AL before the onset of symptoms, thus reducing associated morbidity.

A long-term prospective study of the efficacy and safety of endoscopic septotomy using the LigaSure® system for the treatment of Zenker's diverticulum.

BACKGROUND AND OBJECTIVES: endoscopic septotomy of the cricopharyngeal muscle (ESCM) is a technique used for the treatment of Zenker's diverticulum (ZD). The experience with computerized vascular sealing systems (LigaSure® type) is limited. The objective of this study was to evaluate the efficacy and safety of ESCM using LigaSure®. METHODS: this was a long-term prospective study of 18 patients with ZD, who were referred to our hospital due to ESCM between 2010 and 2016. The severity of the symptoms was determined using the Dakkak-Bennett validated scale for dysphagia and the rest with numerical scales. The rates of relapse and retreatment were evaluated. RESULTS: ESCM with LigaSure® was performed in 17 cases, one case was excluded due to technical difficulties. The median age was 72 years and regurgitation, dysphagia and respiratory symptoms were found in 100%, 89% and 56% of cases, respectively. The median size of the diverticulum was 28 mm (20-60 mm). The median time of the procedure was 35 minutes (25-45 minutes). There were four complications, two hemorrhages and two perforations. The median follow-up was 13 months (range: 12-82 months). Clinical improvements were observed for all symptoms and were maintained 12 months after treatment (p < 0.05). There was no relapse during follow-up in 13 patients. A complete section was not achieved and clinical relapse occurred after a median time of seven months that required retreatment in the remaining patients. CONCLUSIONS: ESCM with LigaSure® may be a safe and effective technique in long-term follow-up situations, with low rates of relapse.

Periendoscopic management of antiplatelet therapy: Prospective evaluation of adherence to guidelines.

INTRODUCCIóN: Adherence to guidelines on the periendoscopic management of antiplatelet therapy (APT) has not been analyzed in detail. Our aim was to assess adherence to guidelines in patients referred to our Endoscopy Unit on a case-by-case basis, describing in detail the detected deviations and identifying areas of improvement. PATIENTS AND METHODS: Cross-sectional study of outpatients consecutively scheduled for an unsedated upper or lower gastrointestinal endoscopy between January and June 2015. Patients on anticoagulant therapy were excluded. RESULTS: 675 patients were evaluated, including 91 (13.5%) patients on APT [upper GI endoscopy 25 (27.5%), lower GI endoscopy 66 (72.5%)]. Contrary to the clinical guidelines, aspirin was discontinued in 25 of the 77 patients previously prescribed the drug (32.5%) but this modification was patient's own decision in 11 cases. Most of the apparent deviations in the management of clopidogrel and dual antiplatelet therapy (DAPT) were not true non-adherence cases. The Primary Care physician modified an APT prescribed by another physician in 8 of 9 cases (88.9%), always in cases with aspirin. No relationship was found between the endoscopic procedure's predicted risk of bleeding or the patient's thrombotic risk and modification of therapy. DISCUSSION: In many patients, the peri-procedural management of APT goes against current guidelines, but some of these inconsistencies cannot be considered true deviations from practice. Identified areas for improvement are increasing patient awareness about APT, disseminating the guidelines in Primary Care, and underscoring the significance of thrombotic risk related to APT withdrawal.

Endoscopist characteristics that influence the quality of colonoscopy.

BACKGROUND AND STUDY AIM: Several factors have been shown to be related to colonoscopy quality; however, little is known about the effects of endoscopist factors. This study analyzed the influence of endoscopist-related characteristics on quality indicators for colonoscopy. PATIENTS AND METHODS: The study included 48 endoscopists who each performed at least 20 colonoscopies in the colonoscopy arm of a randomized controlled trial comparing fecal immunochemical test vs. colonoscopy in colorectal cancer screening. These endoscopists performed a total of 3838 procedures in the trial. The following were calculated for each endoscopist: adenoma detection rate (ADR), advanced ADR, proximal ADR, distal ADR, and adenoma per colonoscopy rate (APCR). The characteristics of endoscopists were assessed with regard to colonoscopy quality using multivariate regression analysis. Endoscopist characteristics included age, sex, exclusive endoscopy practice, years as a physician, years as a specialist, specialty, total (life-long) number of colonoscopies performed, annual colonoscopy volume, number of hours/week dedicated to endoscopy and number of educational activities in the previous year. RESULTS: Factors associated with ADR were age of the endoscopist (odds ratio [OR] 1.11, 95 % confidence interval [CI] 1.01 - 1.21; P = 0.01) and life-long number of colonoscopies (OR 1.06, 95 %CI 1.01 - 1.11; P = 0.01). Only exclusive dedication to endoscopy practice was found to be independently related to proximal ADR (OR 1.71, 95 %CI 1.15 - 2.74; P = 0.001). Life-long number of colonoscopies was independently related to detection of distal adenomas (OR 1.07, 95 %CI 1.01 - 1.13; P = 0.01). None of the analyzed endoscopist characteristics was associated with advanced ADR or APCR. CONCLUSIONS: This study found that the experience of the endoscopist and exclusive dedication to endoscopy practice, but not annual colonoscopy volume, were associated with better colonoscopy quality.

Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening.

BACKGROUND: Colonoscopy and fecal immunochemical testing (FIT) are accepted strategies for colorectal-cancer screening in the average-risk population. METHODS: In this randomized, controlled trial involving asymptomatic adults 50 to 69 years of age, we compared one-time colonoscopy in 26,703 subjects with FIT every 2 years in 26,599 subjects. The primary outcome was the rate of death from colorectal cancer at 10 years. This interim report describes rates of participation, diagnostic findings, and occurrence of major complications at completion of the baseline screening. Study outcomes were analyzed in both intention-to-screen and as-screened populations. RESULTS: The rate of participation was higher in the FIT group than in the colonoscopy group (34.2% vs. 24.6%, P<0.001). Colorectal cancer was found in 30 subjects (0.1%) in the colonoscopy group and 33 subjects (0.1%) in the FIT group (odds ratio, 0.99; 95% confidence interval [CI], 0.61 to 1.64; P=0.99). Advanced adenomas were detected in 514 subjects (1.9%) in the colonoscopy group and 231 subjects (0.9%) in the FIT group (odds ratio, 2.30; 95% CI, 1.97 to 2.69; P<0.001), and nonadvanced adenomas were detected in 1109 subjects (4.2%) in the colonoscopy group and 119 subjects (0.4%) in the FIT group (odds ratio, 9.80; 95% CI, 8.10 to 11.85; P<0.001). CONCLUSIONS: Subjects in the FIT group were more likely to participate in screening than were those in the colonoscopy group. On the baseline screening examination, the numbers of subjects in whom colorectal cancer was detected were similar in the two study groups, but more adenomas were identified in the colonoscopy group. (Funded by Instituto de Salud Carlos III and others; ClinicalTrials.gov number, NCT00906997.).

Rate of detection of advanced neoplasms in proximal colon by simulated sigmoidoscopy vs fecal immunochemical tests.

BACKGROUND & AIMS: We compared the ability of biennial fecal immunochemical testing (FIT) and one-time sigmoidoscopy to detect colon side-specific advanced neoplasms in a population-based, multicenter, nationwide, randomized controlled trial. METHODS: We identified asymptomatic men and women, 50-69 years old, through community health registries and randomly assigned them to groups that received a single colonoscopy examination or biennial FIT. Sigmoidoscopy yield was simulated from results obtained from the colonoscopy group, according to the criteria proposed in the UK Flexible Sigmoidoscopy Trial for colonoscopy referral. Patients who underwent FIT and were found to have ≥75 ng hemoglobin/mL were referred for colonoscopy. Data were analyzed from 5059 subjects in the colonoscopy group and 10,507 in the FIT group. The main outcome was rate of detection of any advanced neoplasm proximal to the splenic flexure. RESULTS: Advanced neoplasms were detected in 317 subjects (6.3%) in the sigmoidoscopy simulation group compared with 288 (2.7%) in the FIT group (odds ratio for sigmoidoscopy, 2.29; 95% confidence interval, 1.93-2.70; P = .0001). Sigmoidoscopy also detected advanced distal neoplasia in a higher percentage of patients than FIT (odds ratio, 2.61; 95% confidence interval, 2.20-3.10; P = .0001). The methods did not differ significantly in identifying patients with advanced proximal neoplasms (odds ratio, 1.17; 95% confidence interval, 0.78-1.76; P = .44). This was probably due to the lower performance of both strategies in detecting patients with proximal lesions (sigmoidoscopy detected these in 19.1% of patients and FIT in 14.9% of patients) vs distal ones (sigmoidoscopy detected these in 86.8% of patients and FIT in 33.5% of patients). Sigmoidoscopy, but not FIT, detected proximal lesions in lower percentages of women (especially those 50-59 years old) than men. CONCLUSIONS: Sigmoidoscopy and FIT have similar limitations in detecting advanced proximal neoplasms, which depend on patients' characteristics; sigmoidoscopy underperforms for women 50-59 years old. Screening strategies should be designed on the basis of target population to increase effectiveness and cost-effectiveness. ClinicalTrials.gov number: NCT00906997.

Modifiable endoscopic factors that influence the adenoma detection rate in colorectal cancer screening colonoscopies.

BACKGROUND: Adenoma detection rate (ADR) has become the most important quality indicator for colonoscopy. OBJECTIVE: The aim of this study was to investigate which modifiable factors, directly related to the endoscopic procedure, influenced the ADR in screening colonoscopies. DESIGN: Observational, nested study. SETTING: Multicenter, randomized, controlled trials. PATIENTS: Asymptomatic people aged 50 to 69 years were eligible for a multicenter, randomized, controlled trial designed to compare colonoscopy and fecal immunochemical testing in colorectal cancer screening. A total of 4539 individuals undergoing a direct screening colonoscopy were included in this study. INTERVENTION: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Bowel cleansing, sedation, withdrawal time in normal colonoscopies, and cecal intubation were analyzed as possible predictors of adenoma detection by using logistic regression analysis, adjusted for age and sex. RESULTS: In multivariate analysis, after adjustment for age and sex, factors independently related to the ADR were a mean withdrawal time longer than 8 minutes (odds ratio [OR] 1.51; 95% CI, 1.17-1.96) in normal colonoscopies and split preparation (OR 1.26; 95% CI, 1.01-1.57). For advanced adenomas, only withdrawal time maintained statistical significance in the multivariate analysis. For proximal adenomas, withdrawal time and cecal intubation maintained independent statistical significance, whereas only withdrawal time longer than 8 minutes and a <10-hour period between the end of preparation and colonoscopy showed independent associations for distal adenomas. LIMITATIONS: Only endoscopic variables have been analyzed. CONCLUSION: Withdrawal time was the only modifiable factor related to the ADR in colorectal cancer screening colonoscopies associated with an increased detection rate of overall, advanced, proximal, and distal adenomas.

Relationship of colonoscopy-detected serrated polyps with synchronous advanced neoplasia in average-risk individuals.

BACKGROUND: Serrated cancers account for 10% to 20% of all colorectal cancers (CRC) and more than 30% of interval cancers. The presence of proximal serrated polyps and large (≥10 mm) serrated polyps (LSP) has been correlated with colorectal neoplasia. OBJECTIVE: To evaluate the prevalence of serrated polyps and their association with synchronous advanced neoplasia in a cohort of average-risk population and to assess the efficacy of one-time colonoscopy and a biennial fecal immunochemical test for reducing CRC-related mortality. This study focused on the sample of 5059 individuals belonging to the colonoscopy arm. DESIGN: Multicenter, randomized, controlled trial. SETTING: The ColonPrev study, a population-based, multicenter, nationwide, randomized, controlled trial. PATIENTS: A total of 5059 asymptomatic men and women aged 50 to 69 years. INTERVENTION: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Prevalence of serrated polyps and their association with synchronous advanced neoplasia. RESULTS: Advanced neoplasia was detected in 520 individuals (10.3%) (CRC was detected in 27 [0.5%] and advanced adenomas in 493 [9.7%]). Serrated polyps were found in 1054 individuals (20.8%). A total of 329 individuals (6.5%) had proximal serrated polyps, and 90 (1.8%) had LSPs. Proximal serrated polyps or LSPs were associated with male sex (odds ratio [OR] 2.08, 95% confidence interval [CI], 1.76-4.45 and OR 1.65, 95% CI, 1.31-2.07, respectively). Also, LSPs were associated with advanced neoplasia (OR 2.49, 95% CI, 1.47-4.198), regardless of their proximal (OR 4.15, 95% CI, 1.69-10.15) or distal (OR 2.61, 95% CI, 1.48-4.58) locations. When we analyzed subtypes of serrated polyps, proximal hyperplasic polyps were related to advanced neoplasia (OR 1.61, 95% CI, 1.13-2.28), although no correlation with the location of the advanced neoplasia was observed. LIMITATIONS: Pathology criteria for the diagnosis of serrated polyps were not centrally reviewed. The morphology of the hyperplasic polyps (protruded or flat) was not recorded. Finally, because of the characteristics of a population-based study carried out in average-risk patients, the proportion of patients with CRC was relatively small. CONCLUSION: LSPs, but not proximal serrated polyps, are associated with the presence of synchronous advanced neoplasia. Further studies are needed to determine the risk of proximal hyperplastic polyps.

The appropriateness of colonoscopies at a teaching hospital: magnitude, associated factors, and comparison of EPAGE and EPAGE-II criteria.

BACKGROUND: The growing demand for colonoscopies and inappropriate colonoscopies have become a significant problem for health care. OBJECTIVES: To assess the appropriateness of colonoscopies and to analyze the association with some clinical and organizational factors. To compare the results of the European Panel of Appropriateness of Gastrointestinal Endoscopy (EPAGE) and the EPAGE-II criteria. DESIGN: Cross-sectional study. SETTING: Endoscopy unit of a teaching hospital in Spain. PATIENTS: Patients referred for colonoscopy, excluding urgent, therapeutic indications, and poor cleansing. MAIN OUTCOME MEASUREMENTS: Appropriateness of colonoscopies according to the EPAGE criteria. RESULTS: From 749 colonoscopies, 619 were included. Most patients were referred by gastroenterologists (66.1%) in an outpatient setting (80.6%). Hematochezia was the most frequent indication (31.5%) followed by colorectal cancer-related indications (27.3%); a clinically relevant diagnosis was established in 41%. Inappropriate use was higher with EPAGE (27.0%) than EPAGE-II (17.4%) criteria. Surveillance after colonic polypectomy and uncomplicated lower abdominal pain were the indications exhibiting higher inadequacy. Inappropriate use was less with older age, in hospitalized patients, with referrals from internal medicine, and in colonoscopies with clinically relevant diagnoses. Agreement between EPAGE and EPAGE-II was fair (weighted κ = 0.31) but improved to moderate (simple κ = 0.60) after grouping appropriate and uncertain levels. LIMITATIONS: The appropriateness criteria are based on panel opinions. Some patients (12%) could not be evaluated with the EPAGE criteria. CONCLUSIONS: Our study identifies substantial colonoscopy overuse, especially in tumor disease surveillance. The EPAGE-II criteria decrease the inappropriate rate and the possibility of overlooking potentially severe lesions.

Factors associated with lesion detection in colonoscopy among different indications.

BACKGROUND AND OBJECTIVE: Different factors may influence colonoscopy performance measures. We aimed to analyze procedure- and endoscopist-related factors associated with detection of colorectal lesions and whether these factors have a similar influence in the context of different colonoscopy indications: positive fecal immunochemical test (+FIT) and post-polypectomy surveillance colonoscopies. METHODS: This multicenter cross-sectional study included adults aged 40-80 years. Endoscopists (N = 96) who had performed ≥50 examinations were assessed for physician-related factors. Adenoma detection rate (ADR), adenomas per colonoscopy rate (APCR), advanced ADR, serrated polyp detection (SDR), and serrated polyps per colonoscopy rate (SPPCR) were calculated. RESULTS: We included 12,932 procedures, with 4810 carried out after a positive FIT and 1967 for surveillance. Of the 96 endoscopists evaluated, 43.8% were women, and the mean age was 41.9 years. The ADR, advanced ADR, and SDR were 39.7%, 17.7%, and 12.8%, respectively. Adenoma detection rate was higher in colonoscopies after a +FIT (50.3%) with a more than doubled advanced ADR compared to non-FIT procedures (27.6% vs. 13.0%) and similar results in serrated lesions (14.7% vs. 13.5%). Among all the detection indicators analyzed, withdrawal time was the only factor independently related to improvement (p < 0.001). Regarding FIT-positive and surveillance procedures, for both indications, withdrawal time was also the only factor associated with a higher detection of adenomas and serrated polyps (p < 0.001). Endoscopist-related factors (i.e., weekly hours dedicated to endoscopy, annual colonoscopy volume and lifetime number of colonoscopies performed) had also impact on lesion detection (APCR, advanced ADR and SPPCR). CONCLUSIONS: Withdrawal time was the factor most commonly associated with improved detection of colonic lesions globally and in endoscopies for + FIT and post-polypectomy surveillance. Physician-related factors may help to address strategies to support training and service provision. Our results can be used for establishing future benchmarking and quality improvement in different colonoscopy indications.

Assessing gut microbial diversity from feces and rectal mucosa.

Gut microbiota is the most complex bacterial community in the human body and its study may give important clues to the etiology of different intestinal diseases. Most studies carried out so far have used fecal samples, assuming that these samples have a similar distribution to the communities present throughout the colon. The present study was designed to test this assumption by comparing samples from the rectal mucosa and feces of nine healthy volunteers by sequencing libraries of 16S rRNA genes. At the family taxonomic level, where rarefaction curves indicate that the observed number of taxa is close to the expected one, we observe under different statistical analyses that fecal and mucosal samples cluster separately. The same is found at the level of species considering phylogenetic information. Consequently, it cannot be stated that both samples from a given individual are of similar composition. We believe that the evidence in support of this statement is strong and that it would not change by increasing the number of individuals and/or performing massive sequencing. We do not expect clinicians to stop using feces for research, but we think it is important to caution them on their potential lack of representativeness with respect to the bacterial biofilm on the rectal mucosa.

Clinical patterns and outcomes of ischaemic colitis: results of the Working Group for the Study of Ischaemic Colitis in Spain (CIE study).

BACKGROUND: There is a lack of prospective studies evaluating the natural history of colonic ischaemia (CI). We performed such a study to evaluate the clinical presentation, outcome, and mortality as well as clinical variables associated with poor prognosis. METHODS: An open, prospective, and multicentre study was conducted in 24 Spanish hospitals serving a population of 3.5 million people. The study included only patients who met criteria for definitive or probable CI. A website (www.colitisisquemica.org) provided logistical support. RESULTS: A total of 364 patients met criteria for inclusion. CI was suspected clinically in only 24.2% of cases. The distribution of clinical patterns was as follows: reversible colopathy (26.1%), transient colitis (43.7%), gangrenous colitis (9.9%), fulminant pancolitis (2.5%), and chronic segmental colitis (17.9%). A total of 47 patients (12.9%) had an unfavorable outcome as defined by mortality and/or the need for surgery. Multivariate analysis identified the following signs as independent risk factors for an unfavorable outcome: abdominal pain without rectal bleeding [odds ratio (OR) 3.9; 95% confidence interval (CI) = 1.6-9.3], non-bloody diarrhoea (OR 10; 95% CI = 3.7-27.4), and peritoneal signs (OR 7.3; 95% CI = 2.7-19.6). Unfavorable outcomes also were more frequent in isolated right colon ischaemia (IRCI) compared with non-IRCI (40.9 vs. 10.3%, respectively; p < 0.0001). The overall mortality rate was 7.7%. CONCLUSIONS: The clinical presentation of CI is very heterogeneous, perhaps explaining why clinical suspicion of this disease is so low. The presence of IRCI, and occurrence of peritoneal signs or onset of CI as severe abdominal pain without bleeding, should alert the physician to a potentially unfavorable course.