Adenoma Detection Rate and Colorectal Cancer Risk in Fecal Immunochemical Test Screening Programs : An Observational Cohort Study.

BACKGROUND: Colorectal cancer (CRC) screening programs based on fecal immunochemical tests (FITs) represent the standard of care for population-based interventions. Their benefit depends on the identification of neoplasia at colonoscopy after FIT positivity. Colonoscopy quality measured by adenoma detection rate (ADR) may affect screening program effectiveness. OBJECTIVE: To examine the association between ADR and postcolonoscopy CRC (PCCRC) risk in a FIT-based screening program. DESIGN: Retrospective population-based cohort study. SETTING: Fecal immunochemical test-based CRC screening program between 2003 and 2021 in northeastern Italy. PATIENTS: All patients with a positive FIT result who had a colonoscopy were included. MEASUREMENTS: The regional cancer registry supplied information on any PCCRC diagnosed between 6 months and 10 years after colonoscopy. Endoscopists' ADR was categorized into 5 groups (20% to 39.9%, 40% to 44.9%, 45% to 49.9%, 50% to 54.9%, and 55% to 70%). To examine the association of ADR with PCCRC incidence risk, Cox regression models were fitted to estimate hazard ratios (HRs) and 95% CIs. RESULTS: Of the 110 109 initial colonoscopies, 49 626 colonoscopies done by 113 endoscopists between 2012 and 2017 were included. After 328 778 person-years follow-up, 277 cases of PCCRC were diagnosed. Mean ADR was 48.3% (range, 23% and 70%). Incidence rates of PCCRC from lowest to highest ADR group were 13.13, 10.61, 7.60, 6.01, and 5.78 per 10 000 person-years. There was a significant inverse association between ADR and PCCRC incidence risk, with a 2.35-fold risk increase (95% CI, 1.63 to 3.38) in the lowest group compared with the highest. The adjusted HR for PCCRC associated with 1% increase in ADR was 0.96 (CI, 0.95 to 0.98). LIMITATION: Adenoma detection rate is partly determined by FIT positivity cutoff; exact values may vary in different settings. CONCLUSION: In a FIT-based screening program, ADR is inversely associated with PCCRC incidence risk, mandating appropriate colonoscopy quality monitoring in this setting. Increasing endoscopists' ADR may significantly reduce PCCRC risk. PRIMARY FUNDING SOURCE: None.

Colonoscopy-related adverse events and mortality in an Italian organized colorectal cancer screening program.

BACKGROUND: Post-colonoscopy adverse events are a key quality indicator in population-based colorectal cancer screening programs, and affect safety and costs. This study aimed to assess colonoscopy-related adverse events and mortality in a screening setting. METHODS: We retrieved data from patients undergoing colonoscopy within a screening program (fecal immunochemical test every 2 years, 50-69-year-olds, or post-polypectomy surveillance) in Italy between 2002 and 2014, to assess the rate of post-colonoscopy adverse events and mortality. Any admission within 30 days of screening colonoscopy was reviewed to capture possible events. Mortality registries were also matched with endoscopy databases to investigate 30-day post-colonoscopy mortality. Association of each outcome with patient-/procedure-related variables was assessed using multivariable analysis. RESULTS: Overall, 117 881 screening colonoscopies (66 584, 56.5 %, with polypectomy) were included. Overall, 497 (0.42 %) post-colonoscopy adverse events occurred: 281 (0.24 %) bleedings (3.69‰/0.68‰, operative/diagnostic procedures) and 65 (0.06 %) perforations (0.75‰/0.29‰, respectively). At multivariable analysis, bleeding was associated with polyp size (≥ 20 mm: odds ratio [OR] 16.29, 95 % confidence interval [CI] 9.38-28.29), proximal location (OR 1.46, 95 %CI 1.14-1.87), and histology severity (high risk adenoma: OR 5.6, 95 %CI 2.43-12.91), while perforation was associated with endoscopic resection (OR 2.91, 95 %CI 1.62-5.22), polyp size (OR 4.34, 95 %CI 1.46-12.92), and proximal location (OR 1.94, 95 %CI 1.12-3.37). Post-colonoscopy mortality occurred in 15 /117 881 cases (1.27/10 000 colonoscopies). CONCLUSIONS: In an organized screening program, post-colonoscopy adverse events were rare but not negligible. The most frequent event was post-polypectomy bleeding, especially after resection of large (≥ 20 mm) and proximal lesions.

Offering people a choice for colorectal cancer screening.

OBJECTIVES: To assess the population coverage and diagnostic yield of offering an immunochemical faecal occult blood test (FIT) to non-responders to a flexible sigmoidoscopy (FS) invitation. DESIGN: A cohort study conducted in a population-based colorectal cancer (CRC) screening programme. In this programme, eligible men and women aged 58 (Turin; 43,748 subjects) or 60 (Verona; 19,970 subjects) are invited, with a personal letter signed by their general practitioner, to undergo an FS. Bowel preparation is limited to a single enema self-administered at home. Subjects in whom one distal polyp >5 mm (≥ 10 mm in Turin) or at least one adenoma (one advanced adenoma or more than two adenomas in Turin) is detected at FS are referred for colonoscopy. People who do not respond to the invitation to undergo an FS are invited to have an FIT (OC-Sensor; Eiken, Tokyo, Japan; single sample, cut-off 100 ng/ml). Attendance rate and neoplasia yield were analysed in four consecutive birth cohorts. RESULTS: Overall participation rate for the FS invitation was 39.3% in Verona and 29.9% in Turin. Of the eligible non-responders to the FS invitation, 19.3% (95% CI 18.9% to 19.7%) underwent an FIT. As a result, the proportion of people undergoing screening by FS or FIT was 55.2% in Verona and 39.3% in Turin, with no gender differences in either centre. FIT detected 8.3% of all advanced adenomas and 20.4% of all CRCs diagnosed at screening. CONCLUSIONS: A strategy involving the sequential offer of FS and FIT is a feasible and efficient approach. FIT in people not attending for FS increases screening uptake and detection of advanced adenomas and CRCs.

Can calprotectin predict relapse risk in inflammatory bowel disease?

OBJECTIVE: Assessing the clinical course of inflammatory bowel disease (IBD) patients consists of periodical clinical evaluations and laboratory tests. We aimed to assess the role of calprotectin tests in predicting clinical relapse in IBD patients. METHODS: Ninety-seven patients with ulcerative colitis (UC) and 65 with Crohn's disease (CD) in clinical remission were prospectively included in the study. A 10-g stool sample was collected for calprotectin assay. The cutoff level was set at 130 mg/kg of feces. Patients were followed up for 1 yr after the test or until relapse. The cumulative proportion of relapses was estimated by the Kaplan-Meier analysis. Statistics for equality of survival distribution were tested using the log-rank test. RESULTS: The calprotectin test was positive in 44 UC patients and 26 of them relapsed within a year, while 11 of 53 UC patients with a negative calprotectin test relapsed within the same time frame. Thirty CD patients had a positive calprotectin test and 13 of them relapsed within a year, as did 7 of the 35 with a negative test result. A significant correlation emerged between a positive calprotectin test and the probability of relapse in UC patients (P= 0.000). In CD patients, only cases of colonic CD showed a significant correlation between a positive calprotectin test and the probability of relapse, i.e., 6 colonic CD patients were positive for the calprotectin test and 4 relapsed (P= 0.02). CONCLUSIONS: Measuring calprotectin may help to identify UC and colonic CD patients at higher risk of clinical relapse.

Oxidative DNA damage in the mucosa of ulcerative colitis increases with disease duration and dysplasia.

BACKGROUND: Chronic inflammation may contribute to cancer risk through the accumulation of specific products as a result of DNA damage. The role of free radical mediated oxidative DNA damage during inflammation was determined in patients with ulcerative colitis by measuring 8-hydroxydeoxyguanosine (8-OHdG). METHODS: Patients with ulcerative colitis were compared according to age, gender, duration and extent of disease, endoscopic and histologic activity, presence or absence of dysplasia/cancer, and biochemical parameters of inflammation. Patients with sporadic colon cancer and irritable bowel syndrome served as controls. Levels of 8-OHdG were assessed by high pressure liquid chromatography with electrochemical detection (mean number of adducts/10(5) dG residues). RESULTS: Patients with ulcerative colitis and dysplasia had significantly higher mucosal 8-OHdG concentrations (P = 0.011). 8-OHdG concentrations were significantly higher in older patients (P = 0.010), patients with long-standing disease (P = 0.015), active endoscopic (P = 0.006) or histologic disease (P = 0.003). Covariance analysis showed significant effect of dysplasia on 8-OHdG levels: values higher than 100 adducts/10(5) dG had a diagnostic value of 80.9% (SE 6.2%). CONCLUSIONS: Oxidative DNA damage accumulates with the duration of the disease in ulcerative colitis reaching maximal increase if dysplastic lesions are found with possible implications for mutagenic and carcinogenic progression.

Role of Magnetic Resonance Enterography in Differentiating between Fibrotic and Active Inflammatory Small Bowel Stenosis in Patients with Crohn's Disease.

OBJECTIVE: To assess the diagnostic accuracy of magnetic resonance imaging (MRI) in prospectively differentiating between fibrotic and active inflammatory small bowel stenosis in patients with Crohn's disease (CD). MATERIALS AND METHODS: A total of 111 patients with histologically proven CD presenting with clinical and plain radiographic signs of small bowel obstruction underwent coronal and axial MRI scans after oral administration of polyethylene glycol solution. A stenosis was judged present if a small bowel segment had >80% lumen reduction as compared to an adjacent normal loop and mural thickening of >3 mm. At the level of the stenosis, both T2 signal intensity and post-gadolinium T1 enhancement were quantified using a 5-point scale (0: very low; 1: low; 2: moderate; 3: high; and 4: very high). A stenosis was considered fibrotic if the sum of the two values (activity score: AS) did not exceed 1. RESULTS: A small bowel stenosis was identified in 48 out of 111 patients. Fibrosis was confirmed at histology in all of the 23 patients with AS of 0 or 1, who underwent surgery within 3 days of the MRI examination. In the remaining 25 patients (AS: 2-8), an active inflammatory stenosis was suspected and remission of the obstructive symptoms was obtained by means of medical treatment. One of these patients (AS: 2), however, underwent surgery after 14 days, due to recurrence. MRI had 95.8% sensitivity, 100% specificity, and 97.9% accuracy in the diagnosis of fibrotic stenosis. CONCLUSION: MRI is reliable in differentiating fibrotic from inflammatory small bowel stenosis in CD.

Efficacy of Infliximab treatment in patients with severe Fistulizing Hidradenitis Suppurativa.

BACKGROUND: The association of Crohn's disease with Fistulizing Hidradenitis Suppurativa (FHS) was established in the 90s. FHS is a chronic disease, characterized by the formation of multiple abscesses and sinus tracts in apocrine gland-bearing areas. The aetiology and pathogenesis is unknown. The disease is painful and often socially disabling implying a poor Quality of Life. Treatment of FHS with Infliximab - a chimeric antibody to TNFα - has recently been proposed as alternative to surgery. AIM: To describe efficacy of Infliximab treatment in the first 2 Danish patients with resistant severe FHS. METHODS: Two patients with severe FHS previously unsuccessfully treated with conventional therapies. Infliximab 5 mg/kg was given as induction treatment. Clinical response was measured by MRI and modified Quality of Life scoring before and after the Infliximab. RESULTS: The first patient obtained partial remission after the first infusion, with 2 active sinus tracts of 20 detected by MRI. The patient became INF dependent and continued on maintenance treatment every 8th week. In total 8 infusions. The second patient obtained partial remission after 3 infusions and did not experience relapse after withdrawal of Infliximab. The clinical findings of remission were underscored by showing improvement on MRI. The Quality of Life has been increased in both patients. CONCLUSION: Infliximab treatment seems to be efficacious in patients with severe FHS. Maintenance treatment may be necessary. Infliximab can lead to improvement in Quality of Life, partial remission of disease verified by closure of fistula in MRI and keeping the patients from mutilating surgery.