Comparison of adenoma miss rate and adenoma detection rate between conventional colonoscopy and colonoscopy with second generation distal attachment cuff: a multicenter, randomized, back-to-back trial.

BACKGROUND AND AIMS: Endocuff VisionTM has been designed to enhance mucosal visualization thereby improving detection of (pre-)malignant colorectal lesions. This multicenter, international, back-to-back, randomized colonoscopy trial compared adenoma detection rate (ADR) and adenoma miss rate (AMR) between Endocuff Vision-assisted colonoscopy (EVC) and conventional colonoscopy (CC). METHODS: Patients aged 40-75 years referred for non-immunochemical fecal occult blood test-based screening, surveillance, or diagnostic colonoscopy were included at ten hospitals and randomized into four groups: Group 1; 2xCC, Group 2; CC followed by EVC, Group 3; EVC followed CC and Group 4; 2xEVC. Primary outcomes included ADR and AMR. RESULTS: A total of 717 patients were randomized of which 661 patients (92.2%) had one and 646 (90.1%) patients had two completed back-to-back colonoscopies. EVC did not significantly improve ADR compared to CC (41.1% [95%-CI;36.1-46.3] versus 35.5% [95%-CI;30.7-40.6], respectively, P=0.125), but EVC did reduced AMR by 11.7% (29.6% [95%-CI;23.6-36.5] versus 17.9% [95%-CI;12.5-23.5], respectively, P=0.049). AMR of 2xCC compared to 2xEVC was also not significantly different (25.9% [95%-CI;19.3-33.9] versus 18.8% [95%-CI;13.9-24.8], respectively, P=0.172). Only 3.7% of the polyps missed during the first procedures had advanced pathologic features. Factors affecting risk of missing adenomas were age (P=0.002), Boston Bowel Preparation Scale (P=0.008) and region where colonoscopy was performed (P<0.001). CONCLUSIONS: Our trial shows that EVC reduces the risk of missing adenomas but does not lead to a significant improved ADR. Remarkably, 25% of adenomas are still missed during conventional colonoscopies, which is not different from miss rates reported 25 years ago; reassuringly, advanced features were only found in 3.7% of these missed lesions. TRAIL REGISTRATION NUMBER: NCT03418948.

Split-dose preparation for colonoscopy increases adenoma detection rate: a randomised controlled trial in an organised screening programme.

OBJECTIVE: Although a split regimen of bowel preparation has been associated with higher levels of bowel cleansing, it is still uncertain whether it has a favourable effect on the adenoma detection rate (ADR). The present study was aimed at evaluating whether a split regimen was superior to the traditional 'full-dose, day-before' regimen in terms of ADR. DESIGN: In a multicentre, randomised, endoscopist-blinded study, 50-69-year-old subjects undergoing first colonoscopy after positive-faecal immunochemical test within an organised colorectal cancer organised screening programmes were 1:1 randomised to receive low-volume 2-L polyethylene glycol (PEG)-ascorbate solution in a 'split-dose' (Split-Dose Group, SDG) or 'day-before' regimen (Day-Before Group, DBG). The primary endpoint was the proportion of subjects with at least one adenoma. Secondary endpoints were the detection rates of advanced adenomas and serrated lesions at per-patient analysis and the total number of lesions. RESULTS: 690 subjects were included in the study. At per-patient analysis, the proportion of subjects with at least one adenoma was significantly higher in the SDG than in the DBG (183/345, 53.0% vs 141/345, 40.9%, relative risk (RR) 1.22, 95% CI 1.03 to 1.46); corresponding figures for advanced adenomas were 26.4% (91/345) versus 20.0% (69/345, RR 1.35, 95% CI 1.06 to 1.73). At per-polyp analysis, the total numbers of both adenomas and advanced adenomas per subject were significantly higher in the SDG (1.15 vs 0.8, p <0.001; 0.36 vs 0.22, p<0.001). CONCLUSIONS: In an organised screening setting, the adoption of a split regimen resulted into a higher detection rate of clinically relevant neoplastic lesions, thus improving the effectiveness of colonoscopy. Based on such evidence, the adoption of a split regimen for colonoscopy should be strongly recommended. CLINICAL TRIAL REGISTRATION NUMBER: NCT02178033.

Efficacy and safety of endoscopic resection of large colorectal polyps: a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of endoscopic resection of large colorectal polyps. DESIGN: Relevant publications were identified in MEDLINE/EMBASE/Cochrane Central Register for the period 1966-2014. Studies in which ≥20 mm colorectal neoplastic lesions were treated with endoscopic resection were included. Rates of postendoscopic resection surgery due to non-curative resection or adverse events, as well as the rates of complete endoscopic removal, invasive cancer, adverse events, recurrence and mortality, were extracted. Study quality was ascertained according to Newcastle-Ottawa Scale. Forest plot was produced based on random effect models. I2 statistic was used to describe the variation across studies due to heterogeneity. Meta-regression analysis was also performed. RESULTS: 50 studies including 6442 patients and 6779 large polyps were included in the analyses. Overall, 503 out of 6442 patients (pooled rate: 8%, 95% CI 7% to 10%, I2=78.6%) underwent surgery due to non-curative endoscopic resection, and 31/6442 (pooled rate: 1%, 95% CI 0.7% to 1.4%, I2=0%) to adverse events. Invasive cancer at histology, non-curative endoscopic resection, synchronous lesions and recurrence accounted for 58%, 28%, 2.2% and 5.9% of all the surgeries, respectively. Endoscopic perforation occurred in 96/6595 (1.5%, 95% CI 1.2% to 1.7%) polyps, while bleeding in 423/6474 (6.5%, 95% CI 5.9% to 7.1%). Overall, 5334 patients entered in surveillance, 502/5836 (8.6%, 95% CI 7.9% to 9.3%) being lost at follow-up. Endoscopic recurrence was detected in 735/5334 patients (13.8%, 95% CI 12.9% to 14.7%), being an invasive cancer in 14/5334 (0.3%, 95% CI 0.1% to 0.4%). Endoscopic treatment was successful in 664/735 cases (90.3%, 95% CI 88.2% to 92.5%). Mortality related with management of large polyps was reported in 5/6278 cases (0.08%, 95% CI 0.01% to 0.15%). CONCLUSIONS: Endoscopic resection of large polyps appeared to be an extremely effective and safe intervention. However, an adequate endoscopic surveillance is necessary for its long-term efficacy.

Faecal microbiota transplantation plus selected use of vancomycin for severe-complicated Clostridium difficile infection: description of a protocol with high success rate.

BACKGROUND: Severe and severe/complicated Clostridium difficile infection (CDI) can result in ICU admission, sepsis, toxic megacolon and death. In this setting, colectomy is the standard of care but it is associated with a 50% mortality. AIM: To evaluate safety and efficacy of a sequential faecal microbiota transplantation (FMT) and antibiotic protocol in severe and severe/complicated CDI patients who are at high risk for colectomy. METHODS: All patients with severe and severe/complicated CDI refractory to oral vancomycin ± rectal vancomycin and intravenous metronidazole therapy were offered FMT. Treatment consisted of sequential FMTs via colonoscopy with the need for repeat FMT and continued vancomycin guided by clinical response and pseudomembranes at colonoscopy. RESULTS: A total of 29 patients underwent FMT between July 2013 and August 2014. The overall treatment response of endoscopic sequential FMT was 93% (27/29), with 100% (10/10) for severe CDI and 89% (17/19) for severe/complicated CDI. A single FMT was performed in 62%, two FMTs were performed in 31% and three FMTs in 7% of patients. The use of non-CDI antibiotics predicted repeat FMT (odds ratio = 17.5). The 30-day all-cause mortality after FMT was 7%, and the cumulative 3-month survival was 76%. Of the two patients who died within 30 days, one underwent colectomy and succumbed to sepsis; the other died from septic shock related to CDI. CONCLUSION: The success of a treatment protocol for severe and severe/complicated involving faecal microbiota transplantation and continued vancomycin in selected patients was high, and it warrants further evaluation.

Systematic review with meta-analysis: the incidence of advanced neoplasia after polypectomy in patients with and without low-risk adenomas.

BACKGROUND: Patients with one to two tubular adenomas <1 cm in size without high-grade dysplasia (low-risk group) are considered at low risk for colorectal cancer. However, it is uncertain whether they have the same risk of subsequent advanced neoplasia as those with no neoplasia at baseline colonoscopy. AIM: To compare incidence of metachronous advanced neoplasia between patients in the low-risk adenoma group and those without neoplasia at index colonoscopy. METHODS: Relevant publications were identified by MEDLINE/EMBASE and other databases for the period 1992-2013. Studies comparing the incidence of post-polypectomy advanced neoplasia (adenomas ≥10 mm/high-grade dysplasia/villous or cancer) between the low-risk group and patients without colorectal neoplasia at the first colonoscopy were included. Detection rates for advanced neoplasia at endoscopic surveillance were extracted. Study quality was ascertained according to Newcastle-Ottawa Scale. Forest plot was produced based on random-effect models. Inter-study heterogeneity was assessed using the I(2) statistic. RESULTS: Seven studies provided data on 11 387 patients. Mean surveillance periods ranged between 2 and 5 years. Altogether, 267 patients with post-polypectomy advanced neoplasia were detected in the two groups. The incidence of advanced neoplasia was 1.6% (119/7308) in those without neoplasia and 3.6% (148/4079) in those with low-risk adenoma, respectively, corresponding to a relative risk of 1.8 (95% CI: 1.3-2.6). Inter-study heterogeneity was only moderate (I(2) : 37%). No publication bias was present. CONCLUSIONS: Patients with low-risk adenomas at baseline had a higher risk of metachronous advanced neoplasia than the group with no adenomas at baseline, though the absolute risk was low in both groups.

Meta-analysis: adherence to colorectal cancer screening and the detection rate for advanced neoplasia, according to the type of screening test.

BACKGROUND: A variety of tests have been proposed for colorectal cancer (CRC), giving rise to uncertainty regarding the optimal approach. The efficacy and effectiveness of different tests are related to both screened participation and the detection rate. AIM: To perform a meta-analysis on adherence and detection rates of CRC screening tests. METHODS: Relevant publications were identified by MEDLINE/EMBASE and other databases for the period 1999-2012. A previous systematic review was used for the period before 1966-1999. RCTs and controlled studies including a direct comparison of the uptake rates among different options for CRC screening were included. Adherence and detection rates for advanced neoplasia and cancer were extracted. Risk for bias was ascertained according to CONSORT guidelines. Forrest plots were produced based on random-effect models. RESULTS: Fourteen studies provided data on 197 910 subjects. Endoscopic strategies were associated with a lower participation (RR: 0.67, 95% CI: 0.56, 0.80) rate, but a higher detection rate of advanced neoplasia (RR: 3.21, 95% CI: 2.38, 4.32) compared with faecal tests. FIT was superior to g-FOBT with regard to both adherence (RR: 1.16, 95% CI 1.03, 1.30) and detection of advanced neoplasia (RR: 2.28, 95% CI 1.68, 3.10) and cancer (RR: 1.96, 95% CI: 1.2, 3.2). CONCLUSION: The superior accuracy of endoscopy compared with faecal tests minimised any impact of the participation rate in determining the detection rate of advanced neoplasia in a screening setting.

Endoscopist-directed propofol administration versus anesthesiologist assistance for colorectal cancer screening: a cost-effectiveness analysis.

BACKGROUND: Propofol for colonoscopy is largely administered by anesthesiologists or anesthesiology nurses in the United States (US) and Europe. Endoscopist-directed administration of propofol (EDP) by nonanesthesiologists has recently been proposed, with potential savings of anesthetist reimbursement costs. We aimed to assess potential EDP-related benefit in a screening setting. METHODS: In a Markov model the total number of screening and follow-up colonoscopies in a cohort of 100 000 US subjects were estimated. Anesthetist-assisted colonoscopy was compared with an EDP strategy. Model outputs were projected onto the 50 - 80-year-old US population, assuming 27 % as the current uptake for colonoscopy screening. Anesthetist costs were estimated using the mean reimbursement for the corresponding Medicare code (≥ 65-year-olds) and from commercial insurance information (50 - 64-year-olds). The proportion of colonoscopies with anesthesiologist assistance was estimated from the Medicare database. Mean nurse salary was used to estimate the cost of a 2-week EDP training. The absolute number of US endoscopists was estimated by inflating by 33 % the number of board-certified gastroenterologists. No EDP mortality was assumed in the reference scenario, and 0.0008 % mortality in the sensitivity analysis. US census data were adopted. Analogous inputs were used for France to assess EDP-related benefit in a European country. RESULTS: EDP training for 17 166 nurses (one for each US endoscopist) showed a cost of $ 47 million. Cost estimates for anesthesiologist assistance for colonoscopy were $ 95 (Medicare) and $ 450 (non-Medicare commercial insurance), with 34.8 % of colonoscopies requiring anesthesiologist assistance. US implementation of an EDP policy showed a 10-year saving of $ 3.2 billion (Monte Carlo analysis 5 - 95 % percentiles $ 2.7 - $ 11.9 billion). In the sensitivity analysis, assuming 50 % of colonoscopies were anesthetist-assisted showed an EDP benefit of $ 4.6 billion. Assuming a 0.0008 % mortality rate, the incremental cost - effectiveness of anesthetist-assisted colonoscopy versus an EDP policy was $ 1.5 million per life-year gained, supporting EDP as the optimal choice. A 31-fold increase of EDP-related mortality or a 17-fold cost reduction for anesthetist-assisted colonoscopy was required for EDP to become not cost-effective in this scenario. Implementation of an EDP policy in France, within a guaiac-fecal occult blood test (g-FOBT) screening program, was estimated to save € 0.8 billion in 10 years. CONCLUSIONS: The absolute economic benefit of EDP implementation in a screening setting is probably substantial with 10-year savings of $3.2 billion in the US and €0.8 billion in France. The impact of an eventual EDP-related mortality on EDP cost - effectiveness seems marginal. The huge economic and medical resources entailed by anesthetist-assisted colonoscopy could be more efficiently invested in other clinical fields.

Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and work-up of detected findings have not yet been standardized. The aim of this evidence-based and consensus-based guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting.

A quantitative assessment of the risks and cost savings of forgoing histologic examination of diminutive polyps.

BACKGROUND AND AIMS: Endoscopic prediction of polyp histology is rapidly improving to the point where it may not be necessary to submit all polyps for formal histologic assessment. This study aimed to quantify the expected costs and outcomes of removing diminutive polyps without subsequent pathologic assessment. METHODS: Cross-sectional analysis of a colonoscopy database for polyp histology; decision models that quantify effects on guideline-recommended surveillance and subsequent costs and consequences. The database was composed of consecutive colonoscopies from 1999 to 2004 at a single-institution tertiary care center. Patients were those found to have at least one diminutive polyp removed during colonoscopy, irrespective of indication. The main outcome measurements include up-front cost savings resulting from forgoing pathologic assessment; frequency and cost of incorrect surveillance intervals based on errors in histologic assessment; number needed to harm (NNH) for perforation and/or interval cancer. RESULTS: Incorrect surveillance intervals were recommended in 1.9% of cases when tissue was submitted for pathologic assessment and 11.8% of cases when it was not. Based on the annual volume of colonoscopy in the US, the annual up-front cost savings of forgoing the pathologic assessment would exceed a billion dollars. An upper estimate on the downstream costs and consequences of forgoing pathology suggests that less than 10% of the up-front savings would be offset and the NNH exceeds 11000. CONCLUSION: Endoscopic diagnosis of polyp histology during colonoscopy and forgoing pathologic examination would result in substantial up-front cost savings. Downstream consequences of the resulting incorrect surveillance intervals appear to be negligible.

A grading scale to evaluate colon cleansing for the PillCam COLON capsule: a reliability study.

BACKGROUND AND STUDY AIMS: The PillCam COLON capsule (Given Imaging, Ltd., Yoqneam, Israel) is an emerging technology for colon visualization. The aim of this prospective study was to assess the interobserver agreement of a new grading scale to evaluate colon cleansing for capsule use. PATIENTS AND METHODS: Healthy volunteers underwent colon preparation and ingested a PillCam COLON capsule. A RAPID 5 (Given Imaging, Ltd.) video was generated and de-identified, and the colon was divided into five segments. Two cleanliness grading scales were compared: a 2-point scale (adequate and inadequate) and a 4-point grading scale (poor, fair, good, and excellent). For assessment of interobserver variability, two experienced gastroenterologists independently rated the cleansing level for each colon segment and for the entire video. Investigators participated in a calibration session prior to reading the study videos. RESULTS: A total of 40 individuals (aged 40 - 74 years) completed the study. A total of 196 colon video segments were evaluated. Per segment, κ values for the 2-point and 4-point scales were 0.754 and 0.619, respectively, representing good interobserver agreement. For the overall grade of the 40 videos, κ values for the 2-point and 4-point scales were 0.647 and 0.44, respectively. CONCLUSIONS: This new cleanliness grading scale showed good interobserver agreement and may be used with the PillCam COLON capsule to assess preparation quality.

Colorectal anatomy in adults at computed tomography colonography: normal distribution and the effect of age, sex, and body mass index.

BACKGROUND AND STUDY AIMS: Computed tomography colonography (CTC) is an accurate tool for assessing the large intestinal anatomy. Our aims were to determine the normal distribution of in vivo colorectal anatomy and to investigate the effect of age, sex, and body mass index (BMI) on colorectal length. PATIENTS AND METHODS: Asymptomatic adults who underwent primary CTC examination at a single institution over an 8-month period were evaluated. The interactive three-dimensional map was used to determine total and segmental lengths and number of acute-angle flexures. The two-dimensional multiplanar display was used to measure luminal diameters. The effects of age, sex, and BMI on colorectal lengths were examined. RESULTS: The study cohort consisted of 505 consecutive adults (266 women, mean age 56.6 years). Mean total colorectal length was 189.5 +/- 26.3 cm and mean number of acute-angle flexures was 10.9 +/- 2.4. Total length for older adults (> 60 years) did not significantly differ from those who were younger than 60 years ( P = 0.22), although the transverse colon was significantly longer in older adults ( P = 0.04). Women had significantly longer colons than men (193.3 cm vs. 185.4 cm, P = 0.002), whereas overweight adults (BMI > 25) had significantly shorter colons compared with those with BMI

Colon cleansing before colonoscopy: does oral sodium phosphate solution still make sense?

Oral sodium phosphate (NaP) solution has been withdrawn from the market in the United States but remains available for over-the-counter purchase for bowel preparation for colonoscopy in Canada. The present review summarizes recent data regarding the renal toxicity of oral NaP as well as its efficacy and tolerability relative to other preparations. Given the availability of effective alternatives to NaP solution, its use for colonoscopy preparation in Canada should be limited. Candidate patients for oral NaP solution should be assessed for eligibility and preparation instructions should adhere to the current recommendations for maximizing the safety of oral NaP.

Review article: moderate sedation for endoscopy: sedation regimens for non-anaesthesiologists.

BACKGROUND: Moderate sedation is a drug-induced depression of consciousness during which patients respond purposefully to verbal commands with or without light tactile stimulation. Moderate sedation is typically accepted in the anaesthesia community as an appropriate target for sedation by non-anaesthesiologists. AIM: To describe drug regimens that can be successfully and safely targeted to moderate sedation for endoscopy by non-anaesthesiologists. RESULTS: Moderate sedation can be achieved using narcotics and benzodiazepines. There is interest in some countries in propofol for endoscopy, which is often viewed as an agent for deep sedation. Indeed, propofol cannot be targeted to moderate sedation for endoscopy as a single agent because of coughing during upper endoscopy and pain withdrawal responses during colonoscopy. Pre-treatment with low doses of narcotic and/or benzodiazepine blocks these effects, allowing propofol to be targeted to moderate sedation. Fospropofol, a prodrug of propofol in clinical development, can also be targeted to moderate sedation if co-administered with narcotic. CONCLUSION: Moderate sedation provides a safety margin when compared with deep sedation and general anaesthesia. Development of protocols that target agents such as propofol to moderate sedation will expand the sedation agents available to non-anaesthesiologists and help ensure that this expansion occurs safely.

Quality in the technical performance of screening flexible sigmoidoscopy: recommendations of an international multi-society task group.

BACKGROUND: Flexible sigmoidoscopy (FS) is a complex technical procedure performed in a variety of settings, by examiners with diverse professional backgrounds, training, and experience. Potential variation in technical quality may have a profound impact on the effectiveness of FS on the early detection and prevention of colorectal cancer. AIM: We propose a set of consensus and evidence based recommendations to assist the development of continuous quality improvement programmes around the delivery of FS for colorectal cancer screening. RECOMMENDATIONS: These recommendations address the intervals between FS examinations, documentation of results, training of endoscopists, decision making around referral for colonoscopy, policies for antibiotic prophylaxis and management of anticoagulation, insertion of the FS endoscope, bowel preparation, complications, the use of non-physicians as FS endoscopists, and FS endoscope reprocessing. For each of these areas, continuous quality improvement targets are recommended, and research questions are proposed.