Tim D. Belderbos

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.

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.

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.

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 Crohns disease patients and its yield. METHODS A multicentre retrospective study was conducted in Crohns 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.

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.

Risk of post-colonoscopy colorectal cancer due to incomplete adenoma resection: A nationwide, population-based cohort study:

Background Most post-colonoscopy colorectal cancers (PC-CRCs) are thought to develop from missed or incompletely resected adenomas. Aims We aimed to assess the incidence rate of PC-CRC overall and per colorectal segment, as a proxy for PC-CRC due to incomplete adenoma resection, and to identify adenoma characteristics associated with these PC-CRCs. Methods We performed a nationwide, population-based cohort study, including all patients with a first colorectal adenoma between 2000–2010 in the Dutch Pathology Registry (PALGA). Outcomes were the incidence rate of PC-CRC overall and of PC-CRC in the same colorectal segment, occurring between six months and five years after adenoma resection. A multivariable Cox proportional hazard analysis was performed to identify factors associated with PC-CRCs in the same segment. Results We included 107,744 patients (mean age 63.4 years; 53.6% male). PC-CRC was detected in 1031 patients (0.96%) with an incidence rate of 1.88 per 1000 person years. PC-CRC in the same segment was found in 323 of 133,519 adenomas (0.24%) with an incidence rate of 0.56 per 1000 years of follow-up. High-grade dysplasia (hazard ratio (HR) 2.54, 95% confidence interval (CI) 1.99–3.25) and both villous (HR 2.63, 95% CI 1.79–3.87) and tubulovillous histology (HR 1.80, 95% CI 1.43–2.27) were risk factors for PC-CRC in the same segment. Conclusions Approximately one-third of PC-CRCs are found in the same colorectal segment after adenoma resection and could therefore be a consequence of incomplete adenoma resection, occurring in one in 400 adenomas. The risk of PC-CRC in the same segment is increased in adenomas with high-grade dysplasia or (tubulo)villous histology.

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.

Sa1962 Surgical Resection for T1 Colorectal Carcinoma Is Associated With Improved Recurrence Free Survival

Background & Aims Controversy exists on the adequate management in case of pathologically confirmed T1 colorectal carcinoma (pT1 CRC). It is not well known whether recurrence free survival after pT1 CRC is improved by performing primary or secondary surgical resection. We aimed to compare the recurrence free survival between patients undergoing surgical resection versus endoscopic resection or transanal endoscopic microsurgery (TEM) only. Secondary aims were to identify factors associated with surgery and recurrence free survival. Methods We identified all patients diagnosed with pT1 CRC between 1995 and 2011 in the Cancer Registry of the southern part of the Netherlands. Data of these patients were linked to PALGA, the Dutch Pathology Registry. Recurrence was defined as subsequent occurrence of CRC at the same location or site of anastomosis, or distant metastasis originating from the index tumor. Surgery was defined as resection of at least a segment of the colon. Multivariable logistic regression was performed to evaluate patientand tumor characteristics associated with surgery. Cox proportional hazard regression analysis was performed to assess the effect of surgery on the risk of recurrence after adjustment for relevant patient and tumor characteristics. Results A total number of 1,965 patients with pT1 CRC were identified. We excluded 183 patients in whom prevalent CRC with tumor stage >T1 was found or in whom the pT1 stage of the index tumor could not be confirmed in PALGA. Of the remaining 1782 patients, 56% were males and mean age was 68 years (SD 11). Endoscopic resection only was performed in 510 patients (29%); TEM only in 86 patients (5%); and surgery in 1186 patients (67%), of whom 238 (20%) underwent prior endoscopic resection. Surgical resection was more often performed in younger patients (OR per 10 years increase 0.86, 95%-CI 0.78-0.95), between 1995 and 2000 (OR 1.65, 95%-CI 1.27 2.14), and in poorly differentiated (OR 1.71, 95%-CI 1.00 2.98) and right-sided tumors (OR 6.59, 95%-CI 3.95 11.00). One or more positive lymph nodes were found in 89 (8%) of 1186 patients undergoing surgery. In the endoscopic resection / TEM group, 48 recurrences (8%) were found versus 50 recurrences (4%) in the surgery group (p<0.01). Surgical resection was significantly associated with increased recurrence free survival (HR 0.51, 95%-CI 0.34 0.76). A higher recurrence rate was found for pT1 CRC in the rectum (HR 3.35, 95%-CI 1.19 9.45). Conclusions In a large cohort of pT1 CRCs, two thirds of patients underwent primary or secondary surgery, which was more likely to be performed in younger patients with poorly differentiated and right-sided tumors. Surgical resection was associated with improved recurrence free survival, but as not all risk factors were available, further studies are needed to elucidate which patients benefit from surgery.