Index Colonoscopy Research Articles

Impact of nonalcoholic fatty liver disease on the risk of metachronous colorectal neoplasia after polypectomy.

Background/AimsMetabolic syndrome has been reported to be a risk factor for metachronous colorectal neoplasia (CRN). However, the impact of nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, on the development of metachronous CRN after polypectomy has been rarely examined. We evaluated the association between NAFLD and the development of metachronous CRN after polypectomy.MethodsAsymptomatic subjects who underwent abdominal ultrasonography and endoscopic removal of ≥ 1 adenomas at the index colonoscopy between 2010 and 2014, and had a follow-up surveillance colonoscopy until 2017 were analyzed.ResultsOf 6,182 participants, 2,642 (42.7%) had NAFLD at the time of the index colonoscopy. Patients with NAFLD had significantly higher cumulative incidence rates of metachronous overall CRN than those without NAFLD in both men (19.4% vs. 18.2% at 3 years and 49.2% vs. 44.0% at 5 years; p = 0.001) and women (18.7% vs. 10.5% at 3 years and 56.1% vs. 29.8% at 5 years; p < 0.001). Even after adjusting for confounders, NAFLD remained independently associated with an increased risk of metachronous overall CRN in both men (adjusted hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.06 to 1.29) and women (adjusted HR, 1.63; 95% CI, 1.27 to 2.07). Additionally, NAFLD was an independent risk factor for metachronous advanced CRN (ACRN) in women (adjusted HR, 2.61; 95% CI, 1.27 to 5.37).ConclusionsNAFLD is related to an increased risk of metachronous CRN after polypectomy. Especially, women with NAFLD are at an increased risk of developing metachronous ACRN. Our results indicate a possible effect of NAFLD on the pathogenesis of CRN.

ACE (Angiotensin-Converting Enzyme) Inhibitors/Angiotensin Receptor Blockers Are Associated With Lower Colorectal Cancer Risk: A Territory-Wide Study With Propensity Score Analysis.

Whether ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers modify colorectal cancer risk remains controversial. We aimed to determine association between their use and colorectal cancer risk after a negative baseline colonoscopy. This is a territory-wide retrospective cohort study recruiting patients aged ≥40 who had undergone colonoscopy between 2005 and 2013. Exclusion criteria included colorectal cancer detected <6 months of index colonoscopy, prior colorectal cancer, inflammatory bowel disease, and prior colectomy. The primary outcome was colorectal cancer diagnosed between 6 and 36 months after index colonoscopy. Sites of colorectal cancer were categorized as proximal (proximal to splenic flexure) and distal cancer. The adjusted hazard ratio of colorectal cancer with ACE inhibitor/angiotensin receptor blocker use (≥180-day use within 5 years before index colonoscopy) was derived by propensity score regression adjustment of 23 covariates (including patient's factors, concurrent medication use, and endoscopy center's performance). Of 187 897 eligible patients, 30 856 (16.4%) were ACE inhibitors/angiotensin receptor blocker users. Eight hundred fifty-four (0.45%) developed colorectal cancer between 6 and 36 months after index colonoscopy (proximal cancer: 147 [17.2%]). These drugs were associated with lower risk of colorectal cancer that developed <3 years after index colonoscopy (adjusted hazard ratio, 0.78 [95% CI, 0.64-0.96]), but not colorectal cancer that developed >3years (adjusted hazard ratio, 1.18 [95% CI, 0.88-1.57]); every single year increase in the drug use was associated with 5% reduction in adjusted hazard ratio risk. ACE inhibitors/angiotensin receptor blocker were associated with a lower colorectal cancer risk in a duration-response manner.

Relationship between colonic diverticulosis and colon neoplasms in Japanese patients.

Colonic diverticulosis (CD) has been reported to be associated with presence of colon neoplasms (CNs) in Western patients, since most of the associated risk factors are common between them. However, such correlation has not been fully investigated in Asian patients. In this study, the association of CNs with CD was evaluated in a multicenter investigation. We enrolled 5633 patients who underwent both colonoscopy and esophagogastroduodenoscopy due to annual follow-up, screening for positive occult blood testing and abdominal symptoms between January 2016 and December 2017 at three institutions. The relationship between the presence of CNs and CD was investigated, and predictors for presence of CNs were determined by multivariate logistic analysis. The enrolled patients consisted of 1799 (31.9%) with CD (average age 70.0years, male 64.0%) and 3834 without CD (66.0years, male 52.9%), with the prevalence of CNs in those groups 46.6% and 44.2%, respectively (P=0.090). Predictors for early colon cancer were shown to be age (OR 1.02, 95%CI 1.01-1.04, P=0.010), laxatives use (OR 1.76, 95%CI 1.17-2.64, P=0.007), gastric neoplasms (OR 2.16, 95%CI 1.23-3.81, P=0.008), and CD (OR 1.64, 95%CI 1.16-2.31, P=0.005). Early colon cancer in the distal colon was most frequently detected in patients with right-sided CD (RR 2.50, P=0.001). In Japanese patients, early colon cancer was more frequently found in those with as compared to those without CD. The presence of CD may be an important indicator for an index colonoscopy examination to detect colon cancer. (Clinical-trial-registry: UMIN000038985).

Diagnostic yield of early repeat colonoscopy after suboptimal bowel preparation in a fecal immunochemical test-based screening program.

Current guidelines regarding surveillance after screening colonoscopy assume adequate bowel preparation. However, follow-up intervals after suboptimal cleansing are highly heterogeneous. We aimed to determine the diagnostic yield of early repeat colonoscopy in patients with suboptimal bowel preparation in fecal immunochemical test (FIT)-based screening colonoscopy. An observational study including patients who underwent colonoscopy with suboptimal bowel preparation after positive FIT screening and then repeat colonoscopy within 1 year. Suboptimal preparation was defined as a Boston Bowel Preparation Scale (BBPS) score of 1 in any segment. Patients with a BBPS score of 0 in any segment or incomplete examination were excluded. The adenoma detection rate (ADR), advanced ADR (AADR), and colorectal cancer rate were calculated for the index and repeat colonoscopies. Of the 2474 patients with FIT-positive colonoscopy at our center during this period, 314 (12.7 %) had suboptimal preparation. Of the 259 (82.5 %) patients who underwent repeat colonoscopy, suboptimal cleansing persisted in 22 (9 %). On repeat colonoscopy, the ADR was 38.7 % (95 %CI 32.6 % to 44.8 %) and the AADR was 14.9 % (95 %CI 10.5 % to 19.4 %). The per-adenoma miss rate was 27.7 % (95 %CI 24.0 % to 31.6 %), and the per-advanced adenoma miss rate was 17.6 % (95 %CI 13.3 % to 22.7 %). After repeat colonoscopy, the post-polypectomy surveillance recommendation changed from 10 to 3 years in 14.7 % of the patients with previous 10-year surveillance recommendation. Patients with suboptimal bowel preparation on FIT-positive colonoscopy present a high rate of advanced adenomas in repeat colonoscopy, with major changes in post-polypectomy surveillance recommendations.

Postcolonoscopy Colorectal Cancer in Sweden From 2003 to 2012: Survival, Tumor Characteristics, and Risk Factors

The rate of postcolonoscopy colorectal cancer (PCCRC) is a measure of colonoscopy quality, but there are conflicting results from studies of survival times of patients with PCCRC. We assessed survival times of patients with PCCRC and characterized the microscopic and macroscopic features of postcolonoscopy colorectal tumors. We performed a population-based cohort study using data from a database in Sweden, on 458,937 colonoscopies (54.0% women) performed from 2003 through 2012. Rates of colorectal cancer within 3 years of a colonoscopy were calculated based on the World Endoscopy Organization guidelines. Risk factors were evaluated using Poisson regression analysis. We used Cox regression models and Kaplan-Meier analyses, stratified by sex, to assess conditional survival. Logistic regression models were used to evaluate features of postcolonoscopy colorectal tumors, including stage location (right, left, or rectum) differentiation grade (high or low), synchronous tumors, perineural growth, resection margins, and mucinous and vessel characteristics. Within 36 months after a colonoscopy, there were 19,184 individuals who had received a diagnosis of CRC; 1384 of these were PCCRCs (7.2%). The proportion of individuals with PCCRC decreased from 9.4% in 2003 to 6.1% in 2012. The largest risk factors for PCCRC were a prior diagnosis of CRC (relative risk [RR], 3.31; 95% CI, 2.71-4.04), ulcerative colitis (RR, 5.44; 95% CI, 4.75-6.23), Crohn's disease (RR, 3.81; 95% CI, 2.98-4.87), and prior polypectomy (RR, 2.32; 95% CI, 1.97-2.72). Individuals with PCCRCs had shorter survival times than individuals with CRCs detected during the index colonoscopy. Multivariate hazard ratios for PCCRC were 2.75 for men (95% CI, 2.21-3.42) and 2.00 for women (95% CI, 1.59-2.52), respectively. Individuals with left-side PCCRC had shorter survival times than patients with CRC detected during the index colonoscopy. Postcolonoscopy colorectal tumors had increased odds of low differentiation grade (odds ratio, 1.27; 95% CI, 1.09-1.49) compared with colorectal tumors detected during the index colonoscopy. In an analysis of colonoscopies in Sweden, the rate of PCCRCs decreased from 9.4% in 2003 to 6.1% in 2012. Diseases that require surveillance (such as prior colorectal neoplasms and inflammatory bowel diseases) are the largest risk factors for PCCRC. Patients with PCCRC have shorter survival times than patients with CRC detected during their initial colonoscopy-especially women and patients with left-side tumors.

Mo1690 ENDOSCOPIST-RELATED FEATURES ASSOCIATED WITH METACHRONOUS ADENOMA DETECTION ON SURVEILLANCE COLONOSCOPIES

Patients with a history of a colon adenoma are at risk of showing metachronous adenomas on surveillance colonoscopies. The risk of such a finding - and thus the interval of time in which surveillance colonoscopy should be carried out – is estimated upon the number and histologic type of resected adenomas. However, other factors could influence the risk of metachronous adenoma detection on surveillance colonoscopies. To describe the prevalence of metachronous colon adenomas and the potential factors associated with it. Endoscopy database of our institution was reviewed from January 2017 to March 2019. Patients undertaking a surveillance colonoscopy were enrolled. The prevalence of metachronous adenomas on patients fulfilling inclusion criteria was described. The following variables were assessed: age, gender, number of adenomas on index colonoscopy, at least one advanced adenoma on index colonoscopy, smoking, obesity, diabetes, family history of colorectal cancer, adequate bowel cleansing on both index and surveillance colonoscopy, adenoma detection rate and multiple adenoma detection rate of the endoscopist who performed index colonoscopy. We included 544 patients who fulfilled inclusion criteria. Both index and surveillance colonoscopies were performed by twelve experienced endoscopists. Overall, 46.32% had at least one metachronous adenoma. There were no differences in terms of age and gender when comparing patients with and without metachronous adenomas. Smoking was more frequent among the former (15.07% versus 6.16%, p=0.02). An advanced adenoma on index colonoscopy (36.51% versus 24.66%, p=0.03) and more than three adenomas on index colonoscopy (28.57% versus 15.07%, p=0.007) were also more prevalent in the metachronous adenoma group. When analysing endoscopists performance-related features, we found that an adenoma detection rate of less than 25 among endoscopists who performed index colonoscopies was more frequent in the metachronous adenoma group (43.65% versus 32.19%, p=0.05). Additionally, a multiple adenoma detection rate of less than 2 was also more frequent in the metachronous adenoma group (56.35% versus 41.78%, p=0.02). On multivariate analysis, advanced adenoma on index colonoscopy [OR 1.73 (1.01-3.02)], more than three adenomas on index colonoscopy [OR 2.29 (1.21-4.32)] and a multiple adenoma detection rate of less than 2 [OR 1.75 (1.01-2.32)] were significantly associated with an increased odds of metachronous adenoma. Some endoscopist performance-related features may have an influence on the odds of identifying metachronous adenomas on surveillance colonoscopies. Further evidence is needed to determine whether these features should be taken into account when deciding time of endoscopic surveillance after adenoma resection.

Mo1662 PATIENT AND ENDOSCOPIC CHARACTERISTICS OF POST-COLONOSCOPY COLON CANCER: A CASE-CONTROL STUDY

There is good evidence that screening programs are successful at reducing the risk of colorectal cancer (CRC). Colonoscopy is the gold standard, however it remains imperfect and colon cancers are still detected after screening or surveillance exams. Developing CRC within 10 years of a prior colonoscopy without cancer is considered post colonoscopy colorectal cancer (PCCRC). Possible explanations include missed lesions, new lesions, incomplete resection, and aggressive biology. The aim of this study was to compare patient characteristics and endoscopic findings of PCCRC cases with those from controls who did not develop CRC. Using a tumor registry dataset, we extracted all CRCs diagnosed at our medical center from 2012–2017. We identified those with prior colonoscopy without cancer within 10 years (index colonoscopy), which were considered PCCRC cases. Major exclusions were prior CRC or hereditary CRC syndromes, IBD, colonoscopies not done at our institution and incomplete polyp resection. Controls were collected from a cohort of all colonoscopies performed from 2003–2019. They never had CRC or high risk adenomas, had colonoscopy for screening indications, and were still followed in our medical record when they were identified (3/2019). The date of index colonoscopy, age and sex for cases was matched in a 3:1 fashion with controls and data were analyzed using conditional logistic regression. Index colonoscopies of 54 PCCRCs were matched with 162 controls. Patient characteristics were similar for both groups (age, sex, smoking, EtOH). The following features were significantly associated with risk of PCCRC: ever history of polyps (OR=3.84), ever history of serrated adenomas (OR=5.33), 2 v 0 polyps (OR=4.55), having a tubular adenoma (TA) (OR=3.53) or sessile serrated adenoma (SSA) (OR=8.49) on index colonoscopy, or having a follow-up recommendation from the endoscopist that did not correlate with the AGA guidelines (OR=5.40). 61% of PCCRC cases had polyps on their index colonoscopy in the same location as their PCCRC. Features that were not significantly associated with risk of PCCRC included: first degree relative with CRC, prep quality, proximal v distal location of polyp, 1 v 0 polyp, hyperplastic polyps, and polyp size (<5mm v 5-9mm). Not surprisingly, patients with TAs/SSAs or multiple polyps have higher risk of developing cancer, including PCCRC. We also show that when comparing TAs to SSAs, there is no significantly elevated risk of developing PCCRC. Given that patient and endoscopic characteristics do not differ between the groups, these data indicate that endoscopy-related factors such as missed or incompletely resected polyps may explain most PCCRC. Increased risk of PCCRC in patients who had incorrect follow-up recommendations should be further investigated.

Mo1678 EVALUATING RECOMMENDATIONS FOR SURVEILLANCE FOR PATIENTS WITH LOW RISK ADENOMAS

Significance: Current practice guidelines recommend surveillance colonoscopies among patients with adenomas removed and intervals vary based on polyp classification. High risk adenomas (HRAs) (≥1 cm, villous features, or high-grade dysplasia) are most likely to progress to cancer and have a recommended 3-year follow-up whereas low risk adenomas (LRAs) (1-2 tubular adenomas ≤1 cm), have a recommended surveillance interval of 5-10 years. Over-performance of surveillance colonoscopies in patients with LRAs increases medical risk and carries significant societal cost. This study examined surveillance recommendations in practice for low risk adenomas. A retrospective chart review in an academic health system of 284 participants [median age: 57.4 (41.6-75.2); 54.6% female] with 1-2 tubular adenomas ≤1 centimeter on index colonoscopy, and a completed surveillance colonoscopy, was performed. Data were collected from exams between January 2011-June 2019. Exclusion criteria included family history of colon cancer, or personal history of polyps, inflammatory bowel disease, adenomas, or colon cancer. The recommended follow-up interval at index colonoscopy and surveillance colonoscopy findings were abstracted. Almost half of participants were recommended to follow up in 5 years (43.3%, n=123). Other recommendations were: 3 years (18.7%), “await pathology results” (19.0%), 5-10 years (8.5%), 3-5 years depending on pathology (3.5%), <3 years (3.2%), 3-5 years (1.4%), 10 years (0.7%), and other (1.8%). The median duration (months) between colonoscopies was 60.07 (12.19 – 88.07). On surveillance, number of LRAs discovered varied: zero (52.1%), one (25.0%), two (12.3%), three (4.6%), four (3.2%), five (0.7%), six or more (1.4%), and uncertain (0.7%). Fifteen participants (5.3%) had one HRA and one (0.4%) had two. No colorectal cancer was detected. Variables significantly associated (p<0.05) with adenomas on surveillance exam included older age, recommendation for follow up after index exam, and worse surveillance exam Boston Bowel Preparation Score (BBPS). Variables with no significant association included sex, race, ethnicity, index exam BBPS, quantity of LRAs and hyperplastic polyps on index exam, LRA size, duration of time between index and surveillance exams, diabetes, smoking history, and body mass index. The majority of participants with LRAs at baseline did not develop HRAs between colonoscopies, supporting a longer surveillance interval. No participants developed colon cancer. Although the current recommended interval is 5-10 years, <10% had a surveillance recommendation of 10 years. Many were told to follow up before 5 years. The findings support the current guidelines of performing a surveillance exam after 5-10 years and suggest that there is low risk in waiting to perform a surveillance exam until closer to the 10 year mark.

Mo1675 COLONOSCOPIC SURVEILLANCE AMONG INDIVIDUALS WITH LARGE TUBULAR ADENOMAS

Individuals with high risk adenomas (HRA) detected during screening colonoscopy have increased risk for the future development of colorectal cancer (CRC). Thus, national guidelines recommend that patients with HRA undergo surveillance colonoscopy at 3 years. Large tubular adenomas (TA), a subcategory of HRA often defined in the literature as size≥2cm, have been associated with greater risk of malignancy. However, little is known about adherence to 3-year surveillance for individuals in this group. In this study, we examined colonoscopic surveillance uptake in patients with large TAs in a large, academic health center to determine if additional strategies are needed to improve surveillance uptake. We identified a random sample of patients: (1) age 50-75; (2) with a diagnosis of HRA on index colonoscopy (1 or more TA with villous histology or high grade dysplasia, TA ≥1 cm, or 3 or more TA of any size) between 3/1/2013 and 1/1/2016; and (3) assignment to a primary care provider (PCP). We then selected the subgroup of patients with TA ≥2cm on either colonoscopy or pathology report. Several trained chart abstractors performed a manual electronic health record (EHR) chart review to collect data on patient demographics (age, gender, race, ethnicity, insurance), clinical factors (family history, healthcare utilization, index colonoscopy findings), and completion and timing of surveillance colonoscopy. The primary outcome was surveillance colonoscopy within 3.5 years of index colonoscopy (a 0.5-year grace period was allowed). We summarized patient characteristics and calculated surveillance uptake. The HRA cohort included 405 patients. There were 36 patients that met large TA size criteria. Mean age was 62.1 years, 63.9% (23/36) were male, and 77.8 (28/36) were white. In all, 50.0% (18/36) completed surveillance by 3.5 years, which is higher than the overall HRA surveillance rate at our institution (42.5%). By 5 years, 58.3% (21/36) of individuals with large TAs had completed surveillance. Surveillance increased sharply from 38.9% (14/36) by 3 years to 50% (18/36) by 3.5 years. We also observed that 36.1% (13/36) TAs were resected piecemeal (Table). For the subgroup of HRA patients with large TAs≥2cm, completion of surveillance colonoscopy was suboptimal, however higher than the mean HRA surveillance rate. In addition, one-third of large TAs were resected piecemeal. Future work will include the development of a larger cohort of large TAs as well as bigger studies to investigate surveillance in this subgroup and factors that influence patients and providers to pursue timely surveillance when polyps are large. In addition, there is need for consensus guidelines and provider education regarding large polyp resection.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Mo1716 SAFETY AND EFFICACY OF COLD SNARE VERSUS HOT SNARE ENDOSCOPIC MUCOSAL RESECTION (EMR) FOR NON-PEDUNCULATED POLYPS ≥ 20MM

Traditional endoscopic mucosal resection (EMR) using hot snare (HS-EMR) is associated with increased risks of bleeding and perforation for large polyps. Cold snare EMR (CS-EMR), which entails submucosal injection followed by cold snare polypectomy, is a newer technique that may be safer due to lack of electrocautery use and may be preferable in high-risk patients (i.e. elderly, patients on anticoagulants/antiplatelets). While data shows CS-EMR may be effective for polyps 10-20mm, there is little data on the use of CS-EMR for large polyps ≥ 20mm. This study aims to assess the safety and efficacy of CS-EMR versus HS-EMR for non-pedunculated polyps ≥ 20mm. We performed a retrospective study at a tertiary care referral center including patients undergoing piecemeal or en bloc CS-EMR or HS-EMR of non-pedunculated polyps ≥ 20mm from January 2015 to March 2019. Adverse events (AEs) were defined by presence of post-polypectomy syndrome, perforation, or delayed bleeding requiring hospitalization, blood transfusions or repeat colonoscopy, within 30 days of index colonoscopy. Efficacy was assessed by the absence of residual adenomatous tissue at follow-up colonoscopy completed from January 2015 to November 2019. Statistical comparison was performed using Fisher’s exact test. 209 patients (97 CS-EMR; 112 HS-EMR) with 220 colonic polyps ≥ 20mm (103 CS-EMR; 117 HS-EMR) were included. In the CS-EMR group, mean patient age was 66.7 years ± 11.3, 57.7% were male, and 36.1% were on anticoagulants/antiplatelets. In the HS-EMR group, mean patient age was 65.9 years ± 11.0, 56.3% were male, and 49.2% were on anticoagulants/antiplatelets. Mean polyp size was 29.3mm ± 10.2 in the CS-EMR group and 25.6mm ± 7.8 in the HS-EMR group. 140 (63.6%) colonic polyps had follow-up surveillance colonoscopies with a median of 271 (56 – 1316) days from index colonoscopy. Residual adenomas during follow-up (determined via biopsy at prior EMR site) were found in 14 (21.8%) CS-EMR cases and 23 (30.2%) HS-EMR cases, which were not significantly different (p=0.337). Post-polypectomy bleeding (9.4% vs. 0%, p < 0.001) and composite adverse events of bleeding, perforation and post-polypectomy syndrome (12.0 % vs. 0%, p < 0.001) were higher in the HS-EMR group compared to the CS-EMR group. CS-EMR appears to be safe for resection of polyps ≥ 20mm with low rates of AEs and similar rates of adenoma clearance compared to HS-EMR. CS-EMR may be especially beneficial in high-risk patients. Significant rates of residual adenoma were present in both groups, which may be due to a tertiary referral center population with polyps previously manipulated, difficult locations including appendiceal orifice, and larger size of polyps. Additional randomized comparative studies are needed to demonstrate the safety and efficacy of CS-EMR compared to HS-EMR polypectomy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The risk of residual or recurring adenoma after piecemeal endoscopic mucosal resection of large non-pedunculated colorectal polyps is predictable.

Piecemeal endoscopic mucosal resection is a safe and effective procedure for the management of large non-pedunculated colorectal polyps. Its major limitation is the possibility of residual or recurrent adenoma and the consequent need for scheduled surveillance colonoscopies, with the implied burden for the patient and health systems. We aimed to evaluate if the Size/Morphology/Site/Access (SMSA) and Sydney EMR Recurrence Tool (SERT) scores are effective in predicting residual/recurrent adenoma after piecemeal endoscopic resection of large non-pedunculated colorectal polyps. Prospective observational cohort study of piecemeal endoscopic mucosal resection of large non-pedunculated colonic polyps performed in a tertiary center. SMSA and SERT scores were calculated in the index colonoscopy and evaluated regarding the ability to predict residual/recurrent adenoma. One hundred fifty-eight procedures were included. Lesions mean size was 31.6 ± 10.1 mm. 65.8% were flat and 61.4% were located in the right colon. Residual/recurrent adenoma was present in 17 (10.8%) cases. SMSA 2 and SERT 0 lesions had 0.0% and 5.7% of residual/recurrent adenoma rate at 6 months, respectively, while SMSA 3-4 and SERT 1-4 lesions had a 11.5% and 14.8% rate, respectively, at 6 months. SMSA grade 2 and SERT grade 0 had a negative predictive value of 100% and 94%, respectively, for residual/recurrent adenoma. SMSA score had an area under the receiver-operating characteristics curve of 0.732 (P = 0.003), while SERT score had a value of 0.730 (P = 0.002) for residual/recurrent adenoma. SMSA and SERT scores are effective tools to identify lesions with a low risk of residual/recurrent adenoma.

Associations between molecular characteristics of colorectal serrated polyps and subsequent advanced colorectal neoplasia.

BRAF mutation and DNA hypermethylation have linked sessile serrated adenomas/polyps (SSA/Ps) to serrated colorectal cancer (CRC) in cross-sectional studies, but they have not been evaluated in a longitudinal study. We aimed to evaluate the associations between molecular markers of serrated polyps and subsequent advanced colorectal neoplasia. Study subjects included Kaiser Permanente Washington members aged 20-75years who received an index colonoscopy between 1/1/1998 and 12/31/2007 and had hyperplastic polyps (HPs) or SSA/Ps according to study pathology review. Polyps from index colonoscopies were removed and assayed for BRAF mutation, CpG island methylator phenotype (CIMP), and MLH1 methylation. Pathology reports and biopsies from the subsequent lower gastrointestinal endoscopy through 1/1/2013 were reviewed for advanced colorectal neoplasia. We identified additional incident CRC cases through linkage to the Seattle-Puget Sound Surveillance Epidemiology and End Results registry. We used generalized estimating equations to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for subsequent advanced colorectal neoplasia, comparing index serrated polyps with different molecular markers. We included 553 individuals with index serrated polyps (420 HPs and 133 SSA/Ps) and 795 subsequent endoscopies. The prevalence of BRAF-mutant, CIMP-high, and MLH1-methylated serrated polyps were 51%, 4%, and 2%, respectively. BRAF and CIMP were not associated with subsequent advanced colorectal neoplasia. MLH1-methylated SSP/As were significantly more likely to have subsequent advanced neoplasia (OR = 4.66, 95% CI 1.06-20.51). Our results suggest that BRAF-mutant and CIMP-high serrated polyps are not associated with subsequent advanced colorectal neoplasia. Among SSA/Ps, MLH1 methylation may be an important marker to identify high-risk CRC precursors.

Increased risk of metachronous large serrated polyps in individuals with 5- to 9-mm proximal hyperplastic polyps: data from the New Hampshire Colonoscopy Registry

Because data on metachronous risk for patients with index proximal 5- to 9-mm hyperplastic polyps (HPs) are limited, the clinical significance of these polyps is unclear. Conversely, published data suggest that sessile serrated polyps (SSPs), traditional serrated adenomas (TSAs), and large (≥1 cm) HPs are high-risk lesions requiring close surveillance. We used data from the New Hampshire Colonoscopy Registry (NHCR) to examine the risk of metachronous large SPs and advanced neoplasias (ANs) in patients with 5- to 9-mm proximal HPs. We included adults with at least 1 polyp resected at index colonoscopy and a surveillance examination 12 months or more after index. Outcomes were risk for metachronous large (≥1 cm) SPs and ANs (≥1 cm, villous elements, high-grade dysplasia, or colorectal cancer [CRC]). Individuals were hierarchically stratified by the most significant index SP. The risks for adults with proximal 5- to 9-mm HPs at index examination were compared with individuals with index findings of large (≥1 cm) HPs or any SSPs or TSAs, nonsignificant HPs (<1 cm in rectosigmoid or<5mm anywhere in colon), high-risk adenomas (AAs or≥3 adenomas, no SPs), and low-risk adenomas (no SPs). We present absolute and adjusted risks of metachronous polyps from a regression model that included age, sex, body mass index, smoking, previous polyp history, family history of CRC, year of diagnosis, endoscopist SP detection rates, and months to surveillance examination. A total of 8560 NHCR participants were included (44.8% women; average age, 59.0 years; standard deviation, 9.1). Similar to those with large HPs or any SSPs/TSAs at index examination (odds ratio, 7.63; 95% confidence interval, 4.78-12.20), individuals with proximal 5- to 9-mm HPs had an elevated risk for metachronous large SPs (odds ratio, 4.77; 95% confidence interval, 2.54-8.94) as compared with adults with low-risk conventional adenomas. NHCR data suggest that similar to adults with large HPs or any SSPs or TSAs at index examination, individuals with index 5- to 9-mm HPs proximal to the sigmoid are at an increased risk for metachronous large SPs. These novel data suggest that close surveillance intervals may be appropriate for patients with 5- to 9-mm proximal HPs.

Comparative systematic review and meta-analysis of 1- to 5-mm versus 6- to 9-mm adenomas on the risk of metachronous advanced colorectal neoplasia

The current guidelines recommend the same surveillance interval for≥3 nonadvanced adenomas (NAAs), without discriminating between diminutive (1-5mm) and small (6-9mm) adenomas. Additionally, the same surveillance interval is recommended for patients with≤2 diminutive NAAs and those with≤2 small NAAs. However, it is questionable whether these recommendations are appropriate. We searched all relevant studies published through September 2019 that examined the risk of metachronous advanced colorectal neoplasia (ACRN) according to the size (diminutive vs small) and the number of adenomas found during an index colonoscopy. Low-risk adenomas (LRAs) were subclassified into 2 categories (LRA-1,≤2 diminutive NAAs; and LRA-2,≤2 small NAAs), and high-risk adenomas (HRAs) were subclassified into 3 categories (HRA-1,≥3 diminutive NAAs; HRA-2,≥3 small NAAs; and HRA-3, advanced adenoma). Eight studies involving 36,142 patients were evaluated. The LRA-2 group had a higher risk of metachronous ACRN than the LRA-1 group (risk ratio, 1.49; 95% confidence interval [CI], 1.23-1.81). Additionally, the HRA-2 and HRA-3 groups had a higher risk of metachronous ACRN than the HRA-1 group (hazard ratios [HRs], 1.51 [95% CI, 1.002-2.28] and 1.92 [95% CI, 1.11-3.33], respectively). However, there was no significant difference between the HRA-1 versus LRA-2 groups (HR, 1.23; 95% CI, .78-1.94). Among the HRA and LRA groups, those with diminutive NAAs had a lower risk of metachronous ACRN than those with small NAAs. We believe that clinical guidelines should consider extending the surveillance intervals in patients with diminutive NAAs only.

Associations Between Mutations in MSH6 and PMS2 and Risk of Surveillance-detected Colorectal Cancer

Lynch syndrome is the most common inherited cause of colorectal cancer (CRC). Contemporary and mutation-specific estimates of CRC-risk in patients undergoing colonoscopy would optimize surveillance strategies. We performed a prospective national cohort study, using data from New Zealand, to assess overall and mutation-specific risk of CRC in patients with Lynch syndrome undergoing surveillance. We performed a prospective study of 381 persons with Lynch syndrome in New Zealand (98 with Lynch-syndrome associated variants in MLH1, 159 in MSH2, 103 in MSH6, and 21 in PMS2). Participants were offered annual colonoscopy starting at age 25 y, and those who underwent 2 or more colonoscopies before December 31, 2017 were included in the final analysis. Patients with previous colonic resection, history of CRC or diagnosis of CRC at index colonoscopy were excluded. Study participants underwent 2061 colonoscopies during 2296 person-y; the median observation-period was 4.43 y and mean-age at enrollment was 43 y. Eighteen patients developed CRC (8 with variants in MLH1, 8 in MSH2, and 2 in MSH6) after a median follow-up period of 6.5 y (range 1-16 y). Eighty-three percent of patients had a surveillance colonoscopy in preceding 24 months before diagnosis of CRC; 94% were diagnosed with stage 0-II CRC and there was no CRC-related mortality. The overall-risk of developing CRC in the 5 y after first surveillance colonoscopy was 2.49% (95% CI, 1.18-5.23); cumulative risks for CRC in patients with Lynch syndrome-associated variants in MLH1, MSH2, or MSH6 by age 70 y were 17.7%, 17.8%, and 8.5%, respectively. Age-adjusted CRC-risk in patients with variants in MSH6 was lower than in MLH1 (hazard ratio, 0.2; 95% CI, 0.04-0.94; P = .02). Of patients with CRC, 33% had an adenomatous polyp resected from same segment in which a colorectal tumor later developed. The risk of CRC in patients with Lynch syndrome-associated mutations in MSH6 or PMS2 was significantly lower than in patients with mutations in MLH1. Incomplete adenomatous polyp resection might be responsible for one third of surveillance-detected CRCs.

Don’t judge a book by its cover: except during optical evaluation

A healthy 41-year-old female was referred for the endoscopic management of a large rectal laterally spreading lesion (LSL). On index colonoscopy, performed for the evaluation of rectal bleeding, multiple proximal...

Cancer-related diagnostic and treatment capabilities of hospitals in the context of racial residential segregation

ObjectiveTo evaluate distribution of hospital-level cancer diagnosis and treatment technologies along dimensions of racial residential segregation. Study designCross-sectional analysis of residential segregation and availability of technologies associated with cancer diagnosis and treatment. MethodsAmerican Hospital Association data were merged with American Community Survey data, and hospital was the unit of analysis. Isolation index and Atkinson's index were calculated for racial residential segregation for the census tract in which the hospital is located based on the composite census block groups. Logistic regression was used to model presence of cancer technologies as a function of percent below poverty (scaled 1–10), number of neighboring hospitals, and rural status. ResultsSegregation measured by isolation index was associated with the availability of some technologies, independent of percentage below 125% poverty line, number of neighboring hospitals, and rural status. Diagnostic cancer technologies, such as CT scan (odds ratio [OR] = 0.928, 95% confidence interval [CI]: 0.894, 0.964), ultrasound (OR = 0.961, 95% CI: 0.927, 0.997), mammography (OR = 0.943, 95% CI: 0.914, 0.974), optical colonoscopy (OR = 0.932, 95% CI: 0.904, 0.961), and full-field digital mammography (OR = 0.948, 95% CI: 0.920, 0.977) and therapeutic cancer technology such as chemo therapy (OR = 0.963, 95% CI: 0.934, 0.992) appear to be less available in neighborhoods with higher isolation index. However, when segregation is measured by Atkinson's index, CT scan (OR = 1.064, 95% CI: 1.010, 1.121), ultrasound (OR = 1.087, 95% CI: 1.035, 1.141), mammography (OR = 1.094, 95% CI: 1.049, 1.141), and optical colonoscopy (OR = 1.053, 95% CI: 1.012, 1.095) are more available in neighborhoods with higher Atkinson's index. ConclusionThese results suggest that cancer diagnostic capabilities in segregated areas are in the pathway between residential segregation and cancer treatment process, and future studies should evaluate individual-level associations.

Nonsteroidal anti-inflammatory drugs but not aspirin are associated with a lower risk of post-colonoscopy colorectal cancer.

Although nonsteroidal anti-inflammatory drugs (NSAIDs) reduce colorectal cancer (CRC) risk, their role in preventing post-colonoscopy CRC (PCCRC) remains undetermined. To investigate whether NSAIDs reduce PCCRC risk after a negative baseline colonoscopy METHODS: This is a retrospective cohort study based on a territory-wide healthcare database of Hong Kong. All patients (aged 40 or above) who underwent colonoscopies between 2005 and 2013 were identified. Exclusion criteria included CRC detected within 6months of index colonoscopy, prior CRC, inflammatory bowel disease and prior colectomy. The primary outcome was PCCRC-3y diagnosed between 6 and 36months after index colonoscopy. Sites of CRC were categorised as proximal (proximal to splenic flexure) and distal. The adjusted hazards ratio (aHR) of PCCRC-3y with NSAID and aspirin use (defined as cumulative use for ≥90days within 5years before index colonoscopy) was derived by propensity score (PS) regression adjustment of 22 covariates (including patient factors, concurrent medication use and endoscopy centre's performance). Of 187897 eligible patients, 21757 (11.6%) were NSAID users. 854 (0.45%) developed PCCRC-3y (proximal cancer: 147 [17.2%]). NSAIDs were associated with a lower PCCRC-3y risk (aHR: 0.54, 95% CI: 0.41-0.70), but not CRC that developed >3years (aHR: 0.78, 95% CI 0.56-1.09). The aHR was 0.48 (95% CI: 0.24-0.95) for proximal and 0.55 (95% CI: 0.40-0.74) for distal cancer. A duration- and frequency response relationship was observed (Ptrend <0.001). For aspirin, the aHR was 1.01 (95% CI: 0.80-1.28). Non-aspirin NSAIDs were associated with lower PCCRC risk after a negative baseline colonoscopy.

Association between improved adenoma detection rates and interval colorectal cancer rates after a quality improvement program

Although colonoscopy reduces colorectal cancer (CRC) risk, interval CRCs (iCRCs) still occur. We aimed to determine iCRC incidence, assess the relationship between adenoma detection rates (ADRs) and iCRC rates, and evaluate iCRC rates over time concomitant with initiation of an institutional colonoscopy quality improvement (QI) program. We performed a retrospective cohort study of patients who underwent colonoscopy at an academic medical center (January 2003 to December 2015). We identified iCRCs through our data warehouse and reviewed charts to confirm appropriateness for study inclusion. iCRC was defined as a cancer diagnosed 6 to 60 months and early iCRC as a cancer diagnosed 6 to 36 months after index colonoscopy. We measured the relationship between provider ADRs and iCRC rates and assessed iCRC rates over time with initiation of a QI program that started in2010. A total of 193,939 colonoscopies were performed over the study period. We identified 186 patients with iCRC. The overall iCRC rate was .12% and the early iCRC rate .06%. Average-risk patients undergoing colonoscopy by endoscopists in the highest ADR quartile (34%-52%) had a 4-fold lower iCRC risk (relative risk, .23; 95% confidence interval, .11-.48) than those undergoing colonoscopy by endoscopists in the lowest quartile (12%-21%). After QI program initiation, overall iCRC rates improved from .15% to .08% (P< .001) and early iCRC rates improved from .07% to .04% (P= .004). We confirmed that iCRC rate is inversely correlated with provider ADR. ADRs increased and iCRC rates decreased over time, concomitant with a QI program focused on split-dose bowel preparation, quality metric measurement, provider education, and feedback. iCRC rate measurement should be considered a feasible, outcomes-driven institutional metric of colonoscopy quality.

Quality indicators in colonoscopy: an evolving paradigm.

The year 1969 marked a revolution in the diagnosis of colorectal cancer (CRC). It is when Dr Wolff developed the colonoscope and quickly realized its potential in both diagnosis and treatment of colonic neoplasms. Over the past 50 years there has been exponential increase in utilization of colonoscopy with over 1 million colonoscopies performed annually throughout Australasia. Endoscopic removal of pre-malignant lesions has been proven to reduce the incidence and mortality of colorectal. Although timing and frequency of surveillance colonoscopy plays a crucial role in risk reduction of CRC, this is dependent upon the findings of the index colonoscopy. The goal of screening colonoscopy is to detect CRC and identify and remove pre-malignant neoplasms that risk progression to CRC. With increasing uptake of bowel screening throughout Australasia, there is increasing pressure to ensure all endoscopists and endoscopy units perform at a universal high-quality. All too often high demand and constant delays compromise colonoscopy quality. Without clear and concise quality indicators with transparent measurement and audit, these flaws can quickly jeopardize screening goals and patient outcomes. This review aims to explore six key quality indicators and explore the evidence behind the current recommended standards. These key indicators include; rate of adequate bowel preparation, caecal intubation rate, adenoma detection rate, withdrawal time, complication rates and surveillance intervals.