Long-term Recurrence-free Survival After Standard Endoscopic Resection Versus Surgical Resection of Submucosal Invasive Colorectal Cancer: A Population-based Study.

BACKGROUND & AIMS: There is controversy over the optimal management for T1 colorectal cancer (T1 CRC). This study compared initial endoscopic resection with or without additional surgery, or initial surgery for T1 CRC, and assessed risk factors for lymph node metastases (LNMs) and long-term recurrence. METHODS: We performed a registration study that included all patients diagnosed with T1 CRC from 1995 through 2011 in the southeast area of The Netherlands (n = 1315). High-risk histology (with regard to LNM) was defined as the presence of poor differentiation, lymphangio-invasion, and/or deep submucosal invasion. The primary outcome measure was the combined rate of local and distant CRC recurrence during a mean follow-up period of 6.6 years. Logistic regression and Cox proportional hazards regression analyses were performed to evaluate independent risk factors for LNM and CRC recurrence, respectively. RESULTS: Endoscopic resection was performed in 590 patients (44.9%); of these, 220 (16.7%) underwent additional surgery. Initial surgery was performed in 725 patients (55.1%). The risk of LNM was higher in T1 CRC with histologic risk factors (15.5% vs 7.1% without histologic risk factors; odds ratio, 2.21; 95% confidence interval, 1.33-3.70). Thirty-day mortality did not differ between patients who received additional surgery (0.9%) and those who underwent only endoscopic resection (1.4%; P = .631). Rates of CRC recurrence were 6.2% (9.8/1000 patient-years) after only endoscopic resection vs 6.4% (9.4/1000 patient-years) after additional surgery (P = .912), and 3.4% (5.2/1000 patient-years) after initial surgery (P = .031). In multivariate analysis, this difference was not significant. The only independent risk factor for long-term recurrence was a positive resection margin (hazard ratio, 6.88; 95% confidence interval, 2.27-20.87). CONCLUSIONS: Based on a population analysis of patients diagnosed with T1 CRC, additional surgery after endoscopic resection should be considered only for patients with high-risk histology or a positive resection margin.

The "golden retriever" study: improving polyp retrieval rates by providing education and competitive feedback.

BACKGROUND AND AIMS: Although optical diagnosis of small colorectal polyps can be achieved at expert centers, accurate prediction of histopathological outcomes has not been achieved in all practice settings. It is therefore important that resected polyps are retrieved for histology. The aims of this study were to evaluate the effect of education and competitive feedback on the overall polyp retrieval rate and to determine which polyp-related and procedure-related factors are associated with retrieval. METHODS: We prospectively included consecutive colonoscopies performed at a single center between April 1, 2013 and April 1, 2014. Patients with inflammatory bowel disease or familial polyposis syndromes were excluded from analysis. Six months after the start of the study, all endoscopists were educated on the importance of polyp retrieval, and a competition was started by publicly providing feedback on the retrieval rate of all endoscopists and the monthly best 3 performers (or "golden retrievers") in particular. We compared overall retrieval rates in the 6 months before and after the start of the competition. RESULTS: The overall polyp retrieval rate improved from 88% (525/594) to 93% (978/1047), comparing consecutive colonoscopies performed in the 6 months before and during the polyp retrieval competition (P < .01). The histopathological outcomes of retrieved polyps were not different before and during the competition. The retrieval rate of right-sided polyps increased from 85% to 95% during the competition (odds ratio [OR], 3.3; 95% confidence interval [CI], 2.0-5.4), whereas the left-sided retrieval rate remained 92%. On multivariable analysis, polyp size greater than 5 mm (OR, 4.1; 95% CI, 1.8-9.6) and in competition resection (OR, 1.8; 95% CI, 1.3-2.6) were significantly associated with polyp retrieval, respectively. CONCLUSION: Providing education and competitive feedback to endoscopists will improve polyp retrieval rates, especially for clinically relevant, right-sided polyps.

Multicenter, randomized, tandem evaluation of EndoRings colonoscopy--results of the CLEVER study.

BACKGROUND AND STUDY AIMS: Adenoma miss rate during colonoscopy has become a widely acknowledged proxy measure for post-colonoscopy colorectal cancer. Among other reasons, this can happen because of inadequate visualization of the proximal aspects of colonic folds and flexures. EndoRings (EndoAid Ltd., Caesarea, Israel) is a silicone-rubber device that is fitted onto the distal end of the colonoscope. Its flexible circular rings engage and mechanically stretch colonic folds during withdrawal. The primary aim of this study was to compare adenoma miss rates between standard colonoscopy and colonoscopy using EndoRings. METHODS: In this multicenter, randomized, tandem colonoscopy study, we performed same-day, back-to-back colonoscopies with EndoRings followed by standard colonoscopy, or vice versa. RESULTS: After exclusion of 10 patients for protocol violations, 116 patients (38.8% female; mean age 58.7) remained for analysis. The adenoma miss rate of EndoRings colonoscopy (7/67; 10.4%) was significantly lower (P<0.001) compared with standard colonoscopy (28/58; 48.3%). Similar results were found for polyp miss rates: EndoRings (9.1%) and standard colonoscopy (52.8%; P<0.001). Mean cecal intubation times (9.3 vs. 8.4 minutes; P=0.142) and withdrawal times (7.4 vs. 7.2 minutes; P=0.286), respectively, were not significantly different between EndoRings and standard colonoscopy. Mean total procedure time was longer with EndoRings than with standard colonoscopy (21.6 vs. 18.5 minutes, P=0.001) as more polyps were removed. CONCLUSIONS: This study demonstrates that colonoscopy with EndoRings has lower adenoma and polyp miss rates than standard colonoscopy, which may improve the efficacy particularly of screening and surveillance colonoscopies. ClinicalTrials.gov NCT01955122.

Comparison of cecal intubation and adenoma detection between hospitals can provide incentives to improve quality of colonoscopy.

BACKGROUND AND STUDY AIMS: Cecal intubation rate (CIR) and adenoma detection rate (ADR) have been found to be inversely associated with the occurrence of post-colonoscopy colorectal cancer. Depicting differences in CIR and ADR between hospitals could provide incentives for quality improvement. The aim of this study was to compare quality parameters of routine colonoscopies between seven hospitals in The Netherlands in order to determine the extent to which possible differences were attributable to procedural and institutional factors. PATIENTS AND METHODS: Consecutive patients undergoing colonoscopy were prospectively included between November 2012 and January 2013 at two academic and five nonacademic hospitals. Patients with inflammatory bowel disease or hereditary colorectal cancer syndromes were excluded. Main outcome measures were CIR and ADR. RESULTS: A total of 3129 patients were included (mean age 59 ±â€Š15 years; 45.5 % male). The majority of patients (86.2 %) had a Boston Bowel Preparation Scale (BBPS) score ≥ 6. Overall CIR was 94.8 %, ranging from 89.4 % to 99.2 % between hospitals. After adjustment for case mix (age, sex, American Society of Anesthesiologists score, and indication for colonoscopy), factors associated with CIR were hospital and a BBPS score ≥ 6. Overall ADR was 31.8 % and varied between hospitals, ranging from 24.8 % to 46.8 %. Independent predictors for ADR were hospital, BBPS score ≥ 6, and cecal intubation. By combining CIR and ADR for each hospital, a colonoscopy quality indicator (CQI) was developed, which can be used by hospitals to stimulate quality improvement. CONCLUSION: Differences in the quality of colonoscopy between hospitals can be demonstrated using CIR and ADR. As both indicators are affected by institution and bowel preparation, a comparison between hospitals based on the newly developed CQI could assist in further improving the quality of colonoscopy.

Local recurrence after endoscopic mucosal resection of nonpedunculated colorectal lesions: systematic review and meta-analysis.

BACKGROUND AND STUDY AIMS: Local recurrence has been observed after endoscopic mucosal resection (EMR) of nonpedunculated colorectal lesions. The indications for follow-up colonoscopy and the optimal time interval are currently unclear. The aims of this systematic review were to assess the frequency of local recurrence after EMR, to identify risk factors for recurrence, and to provide follow-up recommendations. METHODS: A literature search was performed in PubMed, EMBASE, and the Cochrane Library. EMR was defined as endoscopic snare resection after submucosal fluid injection for removal of nonpedunculated adenomas and early carcinomas. Local recurrence was subdivided into early recurrence (detected at the first follow-up colonoscopy) and late recurrence (detected after ≥ 1 previous normal colonoscopy). A random effects meta-analysis was performed to calculate the pooled estimate of risk of recurrence. RESULTS: A total of 33 studies were included. The mean recurrence risk after EMR was 15 % (95 % confidence interval [CI] 12 % - 19 %). Recurrence risk was higher after piecemeal resection (20 %; 95 %CI 16 % - 25 %) than after en bloc resection (3 %; 95 %CI 2 % - 5 %; P < 0.0001). In 15 studies that differentiated between early and late recurrences, 152/173 recurrences (88 %) occurred early. In four studies with follow-up at 3, 6, and ≥ 12 months, 19/25 (76 %) recurrences were detected at 3 months, increasing to 24 (96 %) at 6 months. In multivariable analysis, only piecemeal resection was associated with recurrence (3 of 3 studies). CONCLUSION: Local recurrence after EMR of nonpedunculated colorectal lesions occurs in 3 % of en bloc resections and 20 % of piecemeal resections. Piecemeal resection was the only independent risk factor for recurrence. As more than 90 % of recurrences are detected at 6 months after EMR, we propose that 6 months is the optimal initial follow-up interval.

Optimizing screening for tuberculosis and hepatitis B prior to starting tumor necrosis factor-α inhibitors in Crohn's disease.

BACKGROUND AND AIMS: Treatment with tumor necrosis factor-α (TNF-α) inhibitors in patients with Crohn's disease (CD) is associated with potentially serious infections, including tuberculosis (TB) and hepatitis B virus (HBV). We assessed the cost-effectiveness of extensive TB screening and HBV screening prior to initiating TNF-α inhibitors in CD. METHODS: We constructed two Markov models: (1) comparing tuberculin skin test (TST) combined with chest X-ray (conventional TB screening) versus TST and chest X-ray followed by the interferon-gamma release assay (extensive TB screening) in diagnosing TB; and (2) HBV screening versus no HBV screening. Our base-case included an adult CD patient starting with infliximab treatment. Input parameters were extracted from the literature. Direct medical costs were assessed and discounted following a third-party payer perspective. The main outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity and Monte Carlo analyses were performed over wide ranges of probability and cost estimates. RESULTS: At base-case, the ICERs of extensive screening and HBV screening were €64,340 and €75,760 respectively to gain one quality-adjusted life year. Sensitivity analyses concluded that extensive TB screening was a cost-effective strategy if the latent TB prevalence is more than 12 % or if the false positivity rate of TST is more than 20 %. HBV screening became cost-effective if HBV reactivation or HBV-related mortality is higher than 37 and 62 %, respectively. CONCLUSIONS: Extensive TB screening and HBV screening are not cost-effective compared with conventional TB screening and no HBV screening, respectively. However, when targeted at high-risk patient groups, these screening strategies are likely to become cost-effective.

Implementation of real-time probe-based confocal laser endomicroscopy (pCLE) for differentiation of colorectal polyps during routine colonoscopy.

BACKGROUND AND AIMS: Probe-based confocal laser endomicroscopy (pCLE) is used to differentiate between neoplastic and non-neoplastic colorectal polyps during colonoscopy. We aimed to assess the accuracy of two endoscopists starting to use real-time pCLE for differentiation of colorectal polyps and to determine the negative predictive value (NPV) for neoplasia in polyps ≤ 5 mm. METHODS: Patients undergoing colonoscopy in a tertiary hospital were included in this prospective trial. After a training session, two colonoscopists assessed 50 polyps between August 2012 and April 2014. They sequentially used narrow-band imaging (NBI) and real-time pCLE to differentiate non-adenomatous, adenomatous, and carcinomatous polyps during colonoscopy. Histologic diagnosis by a gastrointestinal pathologist was the gold standard. Results were compared to post-hoc pCLE by a panel of gastroenterologists and pathologists. RESULTS: The accuracy of real-time pCLE was 76 %, compared to 73 % for NBI, and was not significantly different between the first 50 cases (74 %) and the last 50 cases (78 %, P  = 0.64). The accuracy in polyps > 5 mm was 87 % versus 59 % in polyps ≤ 5 mm ( P  = 0.04) and increased from 45 % (13/29) in poor quality images to 86 % (44/51) in fair quality images and 95 % (19/20) in good quality images ( P  < 0.01). The post-hoc pCLE accuracy was 62 %. The NPV for polyps ≤ 5 mm was 58 % for real-time pCLE and 54 % for post-hoc pCLE. CONCLUSION: Although a fair accuracy of real-time pCLE for differentiation of colorectal polyps can be achieved within 50 cases, low NPV and difficulty in obtaining high-quality pCLE images hamper implementation in routine clinical practice.

Screening prior to biological therapy in Crohn's disease: adherence to guidelines and prevalence of infections. Results from a multicentre retrospective study.

BACKGROUND: Screening for opportunistic infections prior to starting biological therapy in patients with inflammatory bowel disease is recommended. AIMS: To assess adherence to screening for opportunistic infections prior to starting biological therapy in Crohn's disease patients and its yield. METHODS: A multicentre retrospective study was conducted in Crohn's disease patients in whom infliximab or adalimumab was started between 2000 and 2010. Screening included tuberculin skin test, interferon-gamma release assay or chest X-ray for tuberculosis. Extended screening included screening for tuberculosis and viral infections. Patients were followed until three months after ending treatment. Primary endpoints were opportunistic and serious infections. RESULTS: 611 patients were included, 91% on infliximab. 463 (76%) patients were screened for tuberculosis, of whom 113 (24%) underwent extended screening. Screening for tuberculosis and hepatitis B increased to, respectively, 90-97% and 36-49% in the last two years. During a median follow-up of two years, 64/611 (9%, 3.4/100 patient-years) opportunistic infections and 26/611 (4%, 1.6/100 patient-years) serious infections were detected. Comorbidity was significantly associated with serious infections (hazard ratio 3.94). CONCLUSIONS: Although screening rates for tuberculosis and hepatitis B increased, screening for hepatitis B was still suboptimal. More caution is required when prescribing biologicals in patients with comorbid conditions.

Adenomas in patients with inflammatory bowel disease are associated with an increased risk of advanced neoplasia.

BACKGROUND: It is still unclear whether inflammatory bowel disease (IBD) patients with adenomas have a higher risk of developing high-grade dysplasia (HGD) or colorectal cancer (CRC) than non-IBD patients with sporadic adenomas. We compared the risk of advanced neoplasia (AN, defined as HGD or CRC) in IBD patients with adenomas to IBD patients without adenomas and patients without IBD with adenomas. METHODS: IBD patients with a histological adenoma diagnosis (IBD + adenoma), age-matched IBD patients without adenoma (IBD-nonadenoma), and adenoma patients without IBD (nonIBD + adenoma) were enrolled in this study. Medical charts were reviewed for adenoma characteristics and development of AN. The endoscopic appearance of the adenomas was characterized as typical (solitary sessile or pedunculated) or atypical (all other descriptions). RESULTS: A total of 110 IBD + adenoma patients, 123 IBD-nonadenoma patients, and 179 nonIBD + adenoma patients were included. Mean duration of follow-up was 88 months (SD ±41). The 5-year cumulative risks of AN were 11%, 3%, and 5% in IBD + adenoma, IBD-nonadenoma, and nonIBD + adenoma patients, respectively (P < 0.01). In IBD patients atypical adenomas were associated with a higher 5-year cumulative risk of AN compared to IBD patients with typical adenomas (18% vs. 7%, P = 0.03). CONCLUSIONS: IBD patients with a histological diagnosis of adenoma have a higher risk of developing AN than adenoma patients without IBD and IBD patients without adenomas. The presence of atypical adenomas in particular was associated with this increased risk, although patients with typical adenomas were found to carry an additional risk as well.