Chromoendoscopy versus autofluorescence imaging for neoplasia detection in patients with longstanding ulcerative colitis (FIND-UC): an international, multicentre, randomised controlled trial

Background: Patients with longstanding ulcerative colitis (UC) undergo regular dysplasia surveillance because of increased colorectal cancer risk. Previous studies demonstrated that autofluorescence imaging (AFI) and chromoendoscopy (CE) increased dysplasia detection. The aim of this study was to determine whether AFI should be further studied as an alternative method for dysplasia surveillance in patients with longstanding UC. Methods: In this prospective international, randomised trial, 210 patients undergoing colonoscopy surveillance for longstanding UC were randomised between 1 August 2013 and 10 March 2017 for inspection with either AFI or CE (105:105). Randomisation was minimised for a previous history of dysplasia and a previous history of primary sclerosing cholangitis. The main outcome was the relative dysplasia detection rate calculated by the ratio of AFI versus CE. This relative dysplasia detection rate was determined for the proportion of UC patients in which at least one dysplastic lesion was detected and for the mean number of dysplastic lesions per patient. The relative dysplasia detection rate needed to be above 0·67 for both outcomes to support performing a subsequent large non-inferiority trial, using an 80% confidence interval. Analysis was performed per protocol. The trial is registered at Netherlands Trial Register (NTR4062). Findings: AFI detected dysplasia in 13 (12·4%) patients, compared to 20 patients (19·1%) with CE. The relative dysplasia detection rate of CE versus AFI for the proportion of UC patients with at least one dysplastic lesion was 0·65 (80% CI; 0·43-0·99). The mean number of detected dysplastic lesions per patient was 0·13 for AFI compared to 0·37 for CE (relative dysplasia detection rate 0·36, 80% CI; 0·21-0·61). Two patients experienced an adverse event (intraprocedural mild bleeding = 1, abdominal pain = 1) in the AFI-arm and three patients (intraprocedural mild bleeding = 2, perforation = 1) in the CE-arm. Interpretation: In this randomised study comparing AFI with CE for dysplasia surveillance in patients with longstanding UC, AFI did not meet criteria for proceeding to a large non-inferiority trial. Therefore, current AFI technology should not be further investigated as an alternative dysplasia surveillance method. Funding: Olympus Europe and Olympus Keymed, Oxford and Nottingham NIHR biomedical research centres

Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT):a multicentre, open-label, randomised, controlled trial

Background: A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia. Methods: In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1–2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment. Findings: Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11–22) before surgery for intravenous iron and 19 days (IQR 13–27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55–2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87–4·58]; p&lt;0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202). Interpretation: Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation. Funding: Vifor Pharma.</p

Study designs to compare new colonoscopic techniques: clinical considerations, data analysis, and sample size calculations

Novel imaging techniques need to be evaluated for their ability to improve the detection of polyps. Critical appraisal of reported studies reveals remarkable differences in study designs, despite their similar objectives. The aim of the current study was to compare frequently used study designs for their required sample size to detect relevant differences in polyp detection rates. Three commonly reported study designs were compared: design 1, the parallel randomized design; design 2, the randomized cross-over design with direct removal of polyps; and design 3, the randomized cross-over design without direct removal of polyps. A total of five different scenarios were analyzed per study design, representing a variety of clinical settings. Each scenario was repeated 1000 times for each study design and the sample size that produced a significant result per study design in each scenario was recorded. In many scenarios, study design 1 required 10-15 times more patients to reach the same statistical power of 80% compared with study design 2. Further reductions in sample size could be achieved when study design 3 was used, although this design is limited by its impracticality. The randomized parallel design requires a larger sample size to achieve equivalent power to the cross-over design. Researchers should carefully consider whether the latter design could be used instead, as it requires a lower number of subjects, although it may be more cumbersome for patients, endoscopists, and researcher

Limited applicability of chromoendoscopy-guided confocal laser endomicroscopy as daily-practice surveillance strategy in Crohn's disease

Patients with longstanding ulcerative colitis have an increased risk for developing colorectal cancer (CRC). Although the risk for ulcerative colitis is well-established, for Crohn's disease data are contradictory. This study aimed to determine the number of patients with Crohn's disease with dysplasia who are undergoing surveillance and to assess the diagnostic accuracy of chromoendoscopy (CE) combined with integrated confocal laser endomicroscopy (iCLE) for differentiating dysplastic versus nondysplastic lesions. Patients with longstanding Crohn's colitis undergoing surveillance colonoscopy were included in this multicenter, prospective, cohort study. Surveillance was performed with CE, and lesions were assessed with iCLE for differentiation. All lesions were removed and sent for pathology as the reference standard. Between 2010 and 2014, a total of 61 patients with Crohn's colitis were included in 5 centers. Seventy-two lesions, of which 7 were dysplastic, were detected in 6 patients (dysplasia detection rate 9.8%); none included high-grade dysplasia or cancer. Combined CE with iCLE for differentiating neoplastic from nonneoplastic lesions had accuracy of 86.7% (95% confidence interval [CI], 78.1-95.3), sensitivity of 42.9% (95% CI, 11.8-79.8), and specificity of 92.4% (95% CI, 80.9-97.6). For CE alone, this was 80.3% (95% CI, 70.7-89.9), 28.6% (95% CI, 5.1-69.7), and 86.4% (95% CI, 80.9-97.6). The study terminated early because of frequent failure of the endoscopic equipment. This study shows a low incidence of dysplastic lesions found during surveillance colonoscopy in patients with longstanding extensive Crohn's colitis. The accuracy of both CE alone and CE in combination with iCLE was relatively good, although the sensitivity for both was poor. Because of frequent equipment failure, iCLE has limited applicability in daily practice as a surveillance strateg

Endoscopically removed rectal NETs: a nationwide cohort study

Purpose: Rectal neuroendocrine tumours (NETs) often present as an incidental finding during colonoscopy. Complete endoscopic resection of low-grade NETs up to 10 mm is considered safe. Whether this is also safe for NETs up to 20 mm is unclear. We performed a nationwide study to determine the risk of lymph node and distant metastases in endoscopically removed NETs. Methods: All endoscopically removed rectal NETs between 1990 and 2010 were identified using the national pathology database (PALGA). Each NET was stratified according to size, grade and resection margin. Follow-up was until February 2016. Results: Between 1990 and 2010, a total of 310 NETs smaller than 20 mm were endoscopically removed. Mean size of NETs was 7.4 mm (SD 3.5). In 49% of NETs (n = 153), no grade (G) could be assessed from the pathology report, 1% was G2 (n = 3), and the remaining NETs were G1. Median follow up was 11.6 years (range 4.9–26.0). During follow-up, 30 patients underwent surgical resection. Lymph node or distant metastasis was seen in 3 patients (1%) which all had a grade 2 NET. Mean time from endoscopic resection to diagnosis of metastases was 6.1 years (95% CI 2.9–9.2). Conclusion: No lymph node or distant metastases were seen in endoscopically removed G1 NETs up to 20 mm during the long follow-up of this nationwide study. This adds evidence to the ENET guideline that endoscopic resection of G1 NETs up to 20 mm appears to be safe

Endoscopic Trimodal Imaging Detects Colonic Neoplasia as Well as Standard Video Endoscopy

BACKGROUND & AIMS: Endoscopic trimodal imaging (ETMI) is a novel endoscopic technique that combines high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow-band imaging (NBI) that has only been studied in academic settings. We performed a randomized, controlled trial in a nonacademic setting to compare ETMI with standard video endoscopy (SVE) in the detection and differentiation of colorectal lesions. METHODS: The study included 234 patients scheduled to receive colonoscopy who were randomly assigned to undergo a colonoscopy in tandem with either ETMI or SVE. In the ETMI group (n = 118), first examination was performed using HRE, followed by AFI. In the other group, both examinations were performed using SVE (n = 116). In the ETMI group, detected lesions were differentiated using AFI and NBI. RESULTS: In the ETMI group, 87 adenomas were detected in the first examination (with HRE), and then 34 adenomas were detected during second inspection (with AFI). In the SVE group, 79 adenomas were detected during the first inspection, and then 33 adenomas were detected during the second inspection. Adenoma detection rates did not differ significantly between the 2 groups (ETMI: 1.03 vs SVE: 0.97, P = .360). The adenoma miss-rate was 29% for HRE and 28% for SVE. The sensitivity, specificity, and accuracy of NBI in differentiating adenomas from nonadenomatous lesions were 87%, 63%, and 75%, respectively; corresponding values for AFI were 90%, 37%, and 62%, respectively. CONCLUSIONS: In a nonacademic setting, ETMI did not improve the detection rate for adenomas compared with SVE. NBI and AFI each differentiated colonic lesions with high levels of sensitivity but low levels of specificit