Eveline Rondagh

Postcolonoscopy colorectal cancers are preventable: a population-based study

Objective The quality of colonoscopy is key for ensuring protection against colorectal cancer (CRC). We therefore aimed to elucidate the aetiology of postcolonoscopy CRCs (PCCRCs), and especially to identify preventable factors. Methods We conducted a population-based study of all patients diagnosed with CRC in South-Limburg from 2001 to 2010 using colonoscopy and histopathology records and data from the Netherlands Cancer Registry. PCCRCs were defined as cancers diagnosed within 5 years after an index colonoscopy. According to location, CRCs were categorised into proximal or distal from the splenic flexure and, according to macroscopic aspect, into flat or protruded. Aetiological factors for PCCRCs were subdivided into procedure-related (missed lesions, inadequate examination/surveillance, incomplete resection) and biology-related (new cancers). Results We included a total of 5107 patients with CRC, of whom 147 (2.9% of all patients, mean age 72.8 years, 55.1% men) had PCCRCs diagnosed on average 26 months after an index colonoscopy. Logistic regression analysis, adjusted for age and gender, showed that PCCRCs were significantly more often proximally located (OR 3.92, 95% CI 2.71 to 5.69), smaller in size (OR 0.78, 95% CI 0.70 to 0.87) and more often flat (OR 1.70, 95% CI 1.18 to 2.43) than prevalent CRCs. Of the PCCRCs, 57.8% were attributed to missed lesions, 19.8% to inadequate examination/surveillance and 8.8% to incomplete resection, while 13.6% were newly developed cancers. Conclusions In our experience, 86.4% of all PCCRCs could be explained by procedural factors, especially missed lesions. Quality improvements in performance of colonoscopy, with special attention to the detection and resection of proximally located flat precursors, have the potential to prevent PCCRCs.

Endoscopic appearance of proximal colorectal neoplasms and potential implications for colonoscopy in cancer prevention

BACKGROUND In everyday practice, the use of colonoscopy for the prevention of colorectal cancer (CRC) is less effective in the proximal than the distal colon. A potential explanation for this is that proximal neoplasms have a more subtle endoscopic appearance, making them more likely to be overlooked. OBJECTIVE To investigate the differences in endoscopic appearance, ie, diminutive size and nonpolypoid shape, of proximal compared with distal colorectal neoplasms. DESIGN Cross-sectional, single-center study. SETTING Endoscopists at the Maastricht University Medical Center in the Netherlands who were previously trained in the detection and classification of nonpolypoid colorectal lesions. PATIENTS Consecutive patients undergoing elective colonoscopy. MAIN OUTCOME MEASUREMENTS Endoscopic appearance, ie, diminutive size (<6 mm) or nonpolypoid shape (height less than half of the diameter) of colorectal adenomas and serrated polyps (SPs), with a focus on adenomas with advanced histology, ie, high-grade dysplasia or early CRC and SPs with dysplasia or large size. RESULTS We included 3720 consecutive patients with 2106 adenomas and 941 SPs. We found that in both men and women, proximal adenomas with high-grade dysplasia/early CRC (n = 181) were more likely to be diminutive or nonpolypoid than distal ones (76.3% vs 26.2%; odds ratio [OR] 9.24; 95% CI, 4.45-19.2; P < .001). Of the proximal adenomas, 84.4% were diminutive or nonpolypoid compared with 68.0% of the distal ones (OR 2.66; 95% CI, 2.14-3.29; P < .001). Likewise, large/dysplastic SPs in the proximal colon were more often nonpolypoid than distal ones (66.2% vs 27.8%; OR 5.51; 95% CI, 2.79-10.9; P < .001). LIMITATIONS Inclusion of both symptomatic and asymptomatic patients. CONCLUSIONS Proximal colorectal neoplasms with advanced histology frequently are small or have a nonpolypoid appearance. These findings support careful inspection of the proximal colon, if quality of cancer prevention with the use of colonoscopy is to be optimized.

Post-Colonoscopy Complications: A Systematic Review, Time Trends, and Meta-Analysis of Population-Based Studies.

OBJECTIVES:Many studies around the world addressed the post-colonoscopy complications, but their pooled prevalence and time trends are unknown. We performed a systematic review and meta-analysis of population-based studies to examine the pooled prevalence of post-colonoscopy complications (“perforation”, “bleeding”, and “mortality”), stratified by colonoscopy indication. Temporal variability in the complication rate was assessed.METHODS:We queried Pubmed, Embase, and the Cochrane library for population-based studies examining post-colonoscopy complications (within 30 days), performed from 2001 to 2015 and published by 1 December 2015. We determined pooled prevalence of perforations, post-colonoscopy bleeding, post-polypectomy bleeding, and mortality.RESULTS:We retrieved 1,074 studies, of which 21 met the inclusion criteria. Overall, pooled prevalences for perforation, post-colonoscopy bleeding, and mortality were 0.5/1,000 (95% confidence interval (CI) 0.4–0.7), 2.6/1,000 (95% CI 1.7–3.7), and 2.9/100,000 (95% CI 1.1–5.5) colonoscopies. Colonoscopy with polypectomy was associated with a perforation rate of 0.8/1,000 (95% CI 0.6–1.0) and a post-polypectomy bleeding rate of 9.8/1,000 (95% CI 7.7–12.1). Complication rate was lower for screening/surveillance than for diagnostic examinations. Time-trend analysis showed that post-colonoscopy bleeding declined from 6.4 to 1.0/1,000 colonoscopies, whereas the perforation and mortality rates remained stable from 2001 to 2015. Overall, considerable heterogeneity was observed in most of the analyses.CONCLUSIONS:Worldwide, the post-colonoscopy complication rate remained stable or even declined over the past 15 years. The findings of this meta-analysis encourage continued efforts to achieve and maintain safety targets in colonoscopy practice.

Endoscopic red flags for the detection of high-risk serrated polyps: an observational study

BACKGROUND AND STUDY AIMS In routine practice, colonoscopy may fail to prevent colorectal cancer (CRC), especially in the proximal colon. A better endoscopic recognition of serrated polyps is important, as this pathway may explain some of the post-colonoscopy cancers. In this study, the endoscopic characteristics of serrated polyps were examined. PATIENT AND METHODS This was a cross-sectional, single-center study of all consecutive patients referred for elective colonoscopy during 1 year. The endoscopists were familiarized with the detection and treatment of nonpolypoid colorectal lesions. Serrated polyps were classified into high risk serrated polyps, defined as dysplastic or large (≥ 6 mm) proximal nondysplastic serrated polyps, and low risk serrated polyps including the remaining nondysplastic serrated polyps. Advanced colorectal neoplasms were defined as multiple (at least three),≥ 10 mm in size, high grade dysplastic adenomas or CRC. RESULTS A total of 2309 patients were included (46.1 % men, mean age 58.4 years), of whom 2.5 % (57) had at least one high risk serrated polyp and 13.9 % (322) had at least one advanced neoplasm. Overall, serrated polyps were more often nonpolypoid than adenomas (16.2 % vs. 11.1 %; P = 0.002). In total, 65 high risk serrated polyps were found, of which 43.1 % (28) displayed a nonpolypoid endoscopic appearance. Patients with advanced neoplasms were more likely to have synchronous high risk serrated polyps than patients without advanced neoplasms: OR 3.66 (95 % CI 2.03 - 6.61, P < 0.001). CONCLUSIONS High risk serrated polyps are frequently nonpolypoid and are associated with synchronous advanced colorectal neoplasms. Advanced colorectal neoplasms may therefore be considered red flags for the presence of high risk serrated polyps. Detection, diagnosis, and treatment of high risk serrated lesions may be important targets to improve the quality of colonoscopic cancer prevention.

Tracking the Molecular Features of Nonpolypoid Colorectal Neoplasms: A Systematic Review and Meta-Analysis

OBJECTIVES:Nonpolypoid colorectal neoplasms (NP-CRNs) are proposed as a major contributor to the occurrence of interval cancers, but their underlying biology remains controversial. We conducted a systematic review and meta-analysis to clarify the major biological events in NP-CRNs.METHODS:We systematically searched for studies examining molecular characteristics of NP-CRNs. We performed random effect meta-analyses. We measured the heterogeneity among studies using I2 and possible publication bias using funnel plots.RESULTS:Fifty-three studies on KRAS, APC, or BRAF mutations, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), or DNA promoter hypermethylation were included. We observed less KRAS mutations (summary odds ratio (OR) 0.30, confidence interval (CI)=0.19–0.46, I2=77.4%, CI=70.1–82.9) and APC mutations (summary OR 0.42, CI=0.24–0.72, I2=22.6%, CI=0.0–66.7) in NP-CRNs vs. protruded CRNs, whereas BRAF mutations were more frequent (summary OR 2.20, CI=1.01–4.81, I2=0%, CI=0–70.8), albeit all with large heterogeneity. Less KRAS mutations were especially found in NP-CRNs subtypes: depressed CRNs (summary OR 0.12, CI=0.05–0.29, I2=0%, CI=0–67.6), non-granular lateral spreading tumors (LSTs-NG) (summary OR 0.61, CI=0.37–1.0, I2=0%, CI=0–74.6), and early nonpolypoid carcinomas (summary OR 0.11, CI=0.06–0.19, I2=0%, CI=0–58.3). MSI frequency was similar in NP-CRNs and protruded CRNs (summary OR 0.99, CI=0.21–4.71, I2=70.3%, CI=38.4–85.7). Data for promoter hypermethylation and CIMP were inconsistent, precluding meaningful conclusions.CONCLUSIONS:This meta-analysis provides indications that NP-CRNs are molecularly different from protruded CRNs. In particular, some subtypes of NP-CRNs, the depressed and LST-NG, are featured by less KRAS mutations than polypoid CRNs. Prospective, multicenter studies are needed to clarify the molecular pathways underlying nonpolypoid colorectal carcinogenesis and potential implications for surveillance intervals.

Endoscopic characterization of sessile serrated adenomas/polyps with and without dysplasia.

BACKGROUND AND STUDY AIMS Sessile serrated adenomas/polyps (SSA/Ps) are precursors of colorectal cancer (CRC), but their endoscopic detection can be difficult. We therefore examined the endoscopic characteristics of SSA/Ps with and without dysplasia in a cross-sectional study. PATIENTS AND METHODS We reviewed clinical, endoscopic, and histopathologic data from patients undergoing colonoscopy between February 2008 and February 2012. We categorized colorectal polyps according to anatomic site, size, and shape, and classified serrated polyps using the World Health Organization (WHO) classification. Multiple logistic regression analyses examined potential differences regarding site, size, and shape between SSA/Ps and colorectal adenomas (overall and advanced only). RESULTS We examined 7433 patients (mean age 59 years, 45.9 % men) with 5968 colorectal polyps. In total, we found 170 SSA/Ps (170/5968, 2.9 %), including 63 SSA/Ps with dysplasia (1.1 %) and 107 SSA/Ps without dysplasia (1.8 %). Compared with SSA/Ps with dysplasia, SSA/Ps without dysplasia were more often proximally located (odds ratio [OR] 3.3, 95 % confidence interval [95 %CI] 1.7 - 6.4), but less often < 6 mm in size (OR 0.6, 95 %CI 0.3 - 1.1). No significant differences were found regarding location between SSA/Ps with dysplasia and advanced adenomas (proximal colon, 47.6 % vs. 40.1 %). However, SSA/Ps with dysplasia were more often < 6 mm in size than advanced adenomas (OR 0.3, 95 %CI 0.2 - 0.5). Of the 63 dysplastic SSA/Ps, 6 (9.5 %) contained high grade dysplasia, but none invasive carcinoma. CONCLUSIONS SSA/Ps with dysplasia are frequently < 6 mm in size, located throughout the colon and 9.5 % of them contain high grade dysplasia. These findings underscore the importance of high quality colonoscopic examination to maximize protection against CRC.

Nonpolypoid colorectal neoplasms: a challenge in endoscopic surveillance of patients with Lynch syndrome

BACKGROUND AND STUDY AIMS Patients with Lynch syndrome may develop colorectal cancer (CRC), despite intensive colonoscopic surveillance. Nonpolypoid colorectal neoplasms might be a major contributor to the occurrence of these cancers. The aim of this case - control study was to compare the endoscopic appearance of colorectal neoplasms between patients with Lynch syndrome and control individuals at average risk for CRC. PATIENTS AND METHODS The endoscopists at the Maastricht University Medical Center were first given training to ensure familiarity with the appearance and classification of nonpolypoid lesions. Patients with Lynch syndrome and patients at average risk for CRC who underwent elective colonoscopy at the Center were prospectively included. Nonpolypoid lesions were defined as lesions with a height of less than half the diameter, and advanced histology was defined as the presence of high grade dysplasia or early cancer. RESULTS A total of 59 patients with Lynch syndrome (mean age 48.7 years, 47.5 % men) and 590 matched controls (mean age 50.2 years, 47.5 % men) were included. In patients with Lynch syndrome, adenomas were significantly more likely to be nonpolypoid than they were in controls: 43.3 % vs. 16.9 % (OR 3.60, 95 %CI 1.90 - 6.83; P < 0.001). This was particularly true for proximal adenomas: 58.1 % vs. 16.3 % (OR 6.93, 95 %CI 2.92 - 16.40; P < 0.001). Adenomas containing advanced histology were more often nonpolypoid in patients with Lynch syndrome than in controls (4/5, 80.0 % vs. 5/17, 29.4 %; P = 0.19). Serrated polyps were also more often nonpolypoid in patients with Lynch syndrome than in controls: 49.2 % vs. 20.4 % (OR 3.57, 95 %CI 1.91 - 6.68; P < 0.001). CONCLUSIONS In patients with Lynch syndrome, colorectal neoplasms are more likely to have a nonpolypoid shape than those from average risk patients, especially in the proximal colon. These findings suggest that proficiency in recognition and endoscopic resection of nonpolypoid colorectal lesions are needed to ensure colonoscopic prevention against CRC in this high risk population.

Development of expertise in the detection and classification of non-polypoid colorectal neoplasia: Experience-based data at an academic GI unit

At its core, quality improvement in gastrointestinal (GI) practice relies on continuous training, education, and information among all health care providers, whether gastroenterologists, GI trainees, endoscopy nurses, or GI pathologists. Over the past few years, it became clear that objective criteria are needed to assess the quality of colonoscopy, such as cecum intubation rate, quality of bowel preparation, withdrawal time, and adenoma detection rate. In this context, development of competence among practicing endoscopists to adequately detect and treat non-polypoid colorectal neoplasms (NP-CRNs) deserves special attention. We describe a summary of the path to develop expertise in detection and management of NP-CRNs, based on experience at our academic GI unit.

Simple clinical risk score identifies patients with serrated polyps in routine practice.

Large, proximal, or dysplastic (LPD) serrated polyps (SP) need accurate endoscopic recognition and removal as these might progress to colorectal cancer. Herewith, we examined the risk factors for having ≥1 LPD SP. We developed and validated a simple SP risk score as a potential tool for improving their detection. We reviewed clinical, endoscopic, and histologic features of serrated polyps in a study of patients undergoing elective colonoscopy (derivation cohort). A self-administered questionnaire was obtained. We conducted logistic regression analyses to identify independent risk factors for having ≥1 LPD SP and incorporated significant variables into a clinical score. We subsequently tested the performance of the SP score in a validation cohort. We examined 2,244 patients in the derivation and 2,402 patients in the validation cohort; 6.3% and 8.2% had ≥1 LPD SP, respectively. Independent risk factors for LPD SPs were age of more than 50 years [OR 2.2; 95% confidence interval (CI), 1.3–3.8; P = 0.004], personal history of serrated polyps (OR 2.6; 95% CI, 1.3–4.9; P = 0.005), current smoking (OR 2.2; 95% CI, 1.4–3.6; P = 0.001), and nondaily/no aspirin use (OR 1.8; 95% CI, 1.1–3.0; P = 0.016). In the validation cohort, a SP score ≥5 points was associated with a 3.0-fold increased odds for LPD SPs, compared with patients with a score <5 points. In the present study, age of more than 50 years, a personal history of serrated polyps, current smoking, and nondaily/no aspirin use were independent risk factors for having LPD SPs. The SP score might aid the endoscopist in the detection of such lesions. Cancer Prev Res; 6(8); 855–63. ©2013 AACR.

Nonpolypoid colorectal neoplasms: Gender differences in prevalence and malignant potential

Abstract Objective. Colonoscopy may fail to prevent colorectal cancer, especially in the proximal colon and in women. Nonpolypoid colorectal neoplasms may potentially explain some of these post-colonoscopy cancers. In the present study, we aimed to examine the prevalence and malignant potential of nonpolypoid colorectal neoplasms in a large population, with special attention to gender and location. Methods. We performed a cross-sectional study of all consecutive patients undergoing elective colonoscopy at a single academic medical center. The endoscopists were familiarized on the detection and treatment of nonpolypoid lesions. Advanced histology was defined by the presence of high-grade dysplasia or early cancer. Results. We included 2310 patients (53.9% women, mean age 58.4 years) with 2143 colorectal polyps. Prevalences of colorectal neoplasms and nonpolypoid colorectal neoplasms were lower in women than in men (20.9% vs. 33.7%, p < 0.001 and 3.0% vs. 5.5%, p = 0.002). In women, nonpolypoid colorectal neoplasms were significantly more likely to contain advanced histology than polypoid ones (OR 2.89, 95% CI 1.24–6.74, p = 0.01), while this was not the case in men (OR 0.91, 95% CI 0.40–2.06, p = 0.83). Proximal neoplasms with advanced histology were more likely to be nonpolypoid than distal ones (OR 4.68, 95% CI 1.54–14.2, p = 0.006). Conclusion. Nonpolypoid mechanisms may play an important role in colorectal carcinogenesis, in both women and men. Although women have fewer colorectal neoplasms than men, they have nonpolypoid colorectal neoplasms, which frequently contain advanced histology.