Quality of Colonoscopy Is Associated With Adenoma Detection and Postcolonoscopy Colorectal Cancer Prevention in Lynch Syndrome.

BACKGROUND & AIMS: Colonoscopy reduces colorectal cancer (CRC) incidence and mortality in Lynch syndrome (LS) carriers. However, a high incidence of postcolonoscopy CRC (PCCRC) has been reported. Colonoscopy is highly dependent on endoscopist skill and is subject to quality variability. We aimed to evaluate the impact of key colonoscopy quality indicators on adenoma detection and prevention of PCCRC in LS. METHODS: We conducted a multicenter study focused on LS carriers without previous CRC undergoing colonoscopy surveillance (n = 893). Incident colorectal neoplasia during surveillance and quality indicators of all colonoscopies were analyzed. We performed an emulated target trial comparing the results from the first and second surveillance colonoscopies to assess the effect of colonoscopy quality indicators on adenoma detection and PCCRC incidence. Risk analyses were conducted using a multivariable logistic regression model. RESULTS: The 10-year cumulative incidence of adenoma and PCCRC was 60.6% (95% CI, 55.5%-65.2%) and 7.9% (95% CI, 5.2%-10.6%), respectively. Adequate bowel preparation (odds ratio [OR], 2.07; 95% CI, 1.06-4.3), complete colonoscopies (20% vs 0%; P = .01), and pan-chromoendoscopy use (OR, 2.14; 95% CI, 1.15-3.95) were associated with significant improvement in adenoma detection. PCCRC risk was significantly lower when colonoscopies were performed during a time interval of less than every 3 years (OR, 0.35; 95% CI, 0.14-0.97). We observed a consistent but not significant reduction in PCCRC risk for a previous complete examination (OR, 0.16; 95% CI, 0.03-1.28), adequate bowel preparation (OR, 0.64; 95% CI, 0.17-3.24), or previous use of high-definition colonoscopy (OR, 0.37; 95% CI, 0.02-2.33). CONCLUSIONS: Complete colonoscopies with adequate bowel preparation and chromoendoscopy use are associated with improved adenoma detection, while surveillance intervals of less than 3 years are associated with a reduction of PCCRC incidence. In LS, high-quality colonoscopy surveillance is of utmost importance for CRC prevention.

Clinical and Pathological Characterization of Lynch-Like Syndrome.

BACKGROUND & AIMS: Lynch syndrome is characterized by DNA mismatch repair (MMR) deficiency. Some patients with suspected Lynch syndrome have DNA MMR deficiencies but no detectable mutations in genes that encode MMR proteins-this is called Lynch-like syndrome (LLS). There is no consensus on management of patients with LLS. We collected data from a large series of patients with LLS to identify clinical and pathology features. METHODS: We collected data from a nationwide-registry of patients with colorectal cancer (CRC) in Spain. We identified patients whose colorectal tumors had loss of MSH2, MSH6, PMS2, or MLH1 (based on immunohistochemistry), without the mutation encoding V600E in BRAF (detected by real-time PCR), and/or no methylation at MLH1 (determined by methylation-specific multiplex ligation-dependent probe amplification), and no pathogenic mutations in MMR genes, BRAF, or EPCAM (determined by DNA sequencing). These patients were considered to have LLS. We collected data on demographic, clinical, and pathology features and family history of neoplasms. The χ2 test was used to analyze the association between qualitative variables, followed by the Fisher exact test and the Student t test or the Mann-Whitney test for quantitative variables. RESULTS: We identified 160 patients with LLS; their mean age at diagnosis of CRC was 55 years and 66 patients were female (41%). The Amsterdam I and II criteria for Lynch syndrome were fulfilled by 11% of cases and the revised Bethesda guideline criteria by 65% of cases. Of the patients with LLS, 24% were identified in universal screening. There were no proportional differences in sex, indication for colonoscopy, immunohistochemistry, pathology findings, or personal history of CRC or other Lynch syndrome-related tumors between patients who met the Amsterdam and/or Bethesda criteria for Lynch syndrome and patients identified in universal screening for Lynch syndrome, without a family history of CRC. CONCLUSIONS: Patients with LLS have homogeneous clinical, demographic, and pathology characteristics, regardless of family history of CRC.

High incidence of advanced colorectal neoplasia during endoscopic surveillance in serrated polyposis syndrome.

BACKGROUND: Serrated polyposis syndrome (SPS) has been associated with an increased risk of colorectal cancer (CRC). Accordingly, intensive surveillance with annual colonoscopy is advised. The aim of this multicenter study was to describe the risk of advanced lesions in SPS patients undergoing surveillance, and to identify risk factors that could guide the prevention strategy. METHODS: From March 2013 to April 2015, 296 patients who fulfilled criteria I and/or III for SPS were retrospectively recruited at 18 centers. We selected patients in whom successful clearing colonoscopy had been performed and who underwent subsequent endoscopic surveillance. Advanced neoplasia was defined as CRC, advanced adenoma, or advanced serrated lesion that were ≥ 10 mm and/or with dysplasia. Cumulative incidence of advanced neoplasia was calculated and independent predictors of advanced neoplasia development were identified. RESULTS: In 152 SPS patients a total of 315 surveillance colonoscopies were performed (median 2, range 1 - 7). The 3-year cumulative incidence of CRC and advanced neoplasia were 3.1 % (95 % confidence interval [CI] 0 - 6.9) and 42.0 % (95 %CI 32.4 - 51.7), respectively. Fulfilling both I + III criteria and the presence of advanced serrated lesions at baseline colonoscopy were independent predictors of advanced neoplasia development (odds ratio [OR] 1.85, 95 %CI 1.03 - 3.33, P  = 0.04 and OR 2.62, 95 %CI 1.18 - 5.81, P  = 0.02, respectively). During follow-up, nine patients (5.9 %) were referred for surgery for invasive CRC (n = 4, 2.6 %) or because of polyp burden (n = 5, 3.3 %). After total colectomy, 17.9 % patients developed advanced neoplasia in the retained rectum. CONCLUSIONS: Patients with SPS have a substantial risk of developing advanced neoplasia under endoscopic surveillance, whereas CRC incidence is low. Personalized endoscopic surveillance based on polyp burden and advanced serrated histology could help to optimize prevention in patients with SPS.

Colorectal cancer risk factors in patients with serrated polyposis syndrome: a large multicentre study.

OBJECTIVE: Serrated polyposis syndrome (SPS) is associated with an increased colorectal cancer (CRC) risk, although the magnitude of the risk remains uncertain. Whereas intensive endoscopic surveillance for CRC prevention is advised, predictors that identify patients who have high CRC risk remain unknown. We performed a multicentre nationwide study aimed at describing the CRC risk in patients with SPS and identifying clinicopathological predictors independently associated with CRC. DESIGN: From March 2013 through September 2014, patients with SPS were retrospectively recruited at 18 Spanish centres. Data were collected from medical, endoscopy and histopathology reports. Multivariate logistic regression was performed to identify CRC risk factors. RESULTS: In 296 patients with SPS with a median follow-up time of 45 months (IQR 26-79.7), a median of 26 (IQR 18.2-40.7) serrated polyps and 3 (IQR 1-6) adenomas per patient were detected. Forty-seven patients (15.8%) developed CRC at a mean age of 53.9±12.8, and 4 out of 47 (8.5%) tumours were detected during surveillance (cumulative CRC incidence 1.9%). Patients with >2 sessile serrated adenomas/polyps (SSA/Ps) proximal to splenic flexure and ≥1 proximal SSA/P with high-grade dysplasia were independent CRC risk factors (incremental OR=2, 95% CI 1.22 to 3.24, p=0.006). Patients with no risk factors showed a 55% decrease in CRC risk (OR=0.45, 95% CI 0.24 to 0.86, p=0.01). CONCLUSIONS: Patients with SPS have an increased risk of CRC, although lower than previously published. Close colonoscopy surveillance in experienced centres show a low risk of developing CRC (1.9% in 5 years). Specific polyp features (SSA/P histology, proximal location and presence of high-grade dysplasia) should be used to guide clinical management.

Diagnostic performance of fecal immunochemical test and sigmoidoscopy for advanced right-sided colorectal neoplasms.

BACKGROUND: Colorectal cancer screening effect on right-sided colorectal neoplasia is limited. We compared fecal immunochemical test and simulated sigmoidoscopy diagnostic accuracy for advanced right-sided neoplasia detection. METHODS: We analyzed 1,292 individuals with complete screening colonoscopy with a fecal immunochemical test determination before colonoscopy. Sigmoidoscopy and "hybrid strategy" (sigmoidoscopy or fecal hemoglobin concentration ≥ 20 µg hemoglobin/g) diagnostic yield were simulated according to UK Flexible Sigmoidoscopy, Screening for COlon REctum (SCORE), and Norwegian Colorectal Cancer Prevention (NORCCAP) trials criteria to complete colonic examination. We compared sensitivity and specificity of both strategies and of "hybrid strategy" for advanced right-sided neoplasia with McNemar test. RESULTS: An advanced right-sided neoplasia was detected in 47 (3.6 %) subjects. A fecal hemoglobin concentration ≥ 20 µg hemoglobin/g was determined in 6.6 % of the subjects and 10.1, 12.7, and 23.5 % met UK, SCORE, and NORCCAP criteria, respectively. Fecal immunochemical test was statistically more specific than sigmoidoscopy strategies (93.8 %, UK 90.3 %, SCORE 87.7 %, NORCCAP 77.8 %; p < 0.001). In contrast, fecal immunochemical test sensitivity for advanced right-sided neoplasia (17 %) was not statistically different than UK (21.3 %; p = 0.7) or SCORE (23.4 %; p = 0.5), although it was inferior than NORCCAP strategy (42.5 %; p < 0.001). Adding fecal immunochemical test to sigmoidoscopy increased number of positives (8.5-25.7 %), sensitivity (10-30 %), and significantly reduced advanced right-sided neoplasia specificity (p < 0.001). CONCLUSIONS: Fecal immunochemical test and sigmoidoscopy diagnostic yield for advanced right-sided neoplasia are low. Fecal immunochemical test is more specific than sigmoidoscopy but less sensitive than sigmoidoscopy according to NORCCAP criteria.

Diagnostic accuracy of fecal immunochemical test in average- and familial-risk colorectal cancer screening.

BACKGROUND: There is little information about the fecal immunochemical test (FIT) in familial-risk colorectal cancer (CRC) screening. OBJECTIVES: The objective of this article is to investigate whether FIT diagnostic accuracy for advanced neoplasia (AN) differs between average and familial-risk (first-degree relative) patients. METHODS: A total of 1317 consecutive participants (595 familial) who collected one stool sample before performing a colonoscopy as a CRC screening test were included. FIT diagnostic accuracy for AN was evaluated with Chi-square test at a 20 µg hemoglobin/g of feces cut-off value. Finally, we determined which variables were independently related to AN. RESULTS: An AN was found in 151 (11.5%) patients. The overall accuracy was not statistically different between both cohorts for AN (88.4%, 91.7%; p = 0.051). At the cut-off stablished, differences in FIT sensitivity (31.1%, 40.6%; p = 0.2) or specificity (96.5%, 97.3%; p = 0.1) were not statistically significant. Finally, independent variables such as sex (male) (odds ratio (OR) 2.1, 95% confidence interval (CI) 1.4-3.1), age (50-65, >65 years) (OR 2.1, 95% CI 1.1-4.3; OR 2.7, 95% CI 1.2-6.1), previous colonoscopy (OR 0.4, 95% CI 0.2-0.9) and FIT ≥20 µg/g feces (OR 17.7, 95% CI 10.8-29.1) were associated with AN diagnosis. CONCLUSIONS: FIT accuracy for AN detection is equivalent in average and familial-risk CRC screening cohorts.

Characteristics of adenomas detected by fecal immunochemical test in colorectal cancer screening.

BACKGROUND: Fecal immunochemical test (FIT) diagnostic accuracy for colorectal adenoma detection in colorectal cancer screening is limited. METHODS: We analyzed 474 asymptomatic subjects with adenomas detected on colonoscopy in two blinded diagnostic tests studies designed to assess FIT diagnostic accuracy. We determined the characteristics of adenomas (number, size, histology, morphology, and location) and the risk of metachronous lesions (according to European guidelines). Finally, we performed a logistic regression to identify those variables independently associated with a positive result. RESULTS: Advanced adenomas were found in 145 patients (75.6% distal and 24.3% only proximal to splenic flexure). Patients were classified as low (59.5%), intermediate (30.2%), and high risk (10.3%) according to European guidelines. At a 100-ng/mL threshold, FIT was positive in 61 patients (12.8%). Patients with advanced adenomas [odds ratio (OR), 8.8; 95% confidence interval (CI), 4.76-16.25], distal advanced adenomas (OR, 6.7; 95% CI, 1.9-8.8), high risk (OR, 20.1; 95% CI, 8.8-45.8), or intermediate risk lesions (OR, 6; 95% CI, 2.9-12.4) had more probabilities to have a positive test. The characteristics of adenomas independently associated were number of adenomas (OR, 1.22; 95% CI, 1.04-1.42), distal flat adenomas (OR, 0.44; 95% CI, 0.21-0.96), pedunculated adenomas (OR, 2.28; 95% CI, 1.48-3.5), and maximum size of distal adenomas (mm; OR, 1.24; 95% CI, 1.16-1.32). CONCLUSIONS: European guidelines classification and adenoma location correlates with the likelihood of a positive FIT result. IMPACT: This information allows us to understand the FIT impact in colorectal cancer prevention. Likewise, it should be taken into account in the development of new colorectal adenomas biomarkers.

Fecal immunochemical test accuracy in average-risk colorectal cancer screening.

AIM: To assess the fecal immunochemical test (FIT) accuracy for colorectal cancer (CRC) and advanced neoplasia (AN) detection in CRC screening. METHODS: We performed a multicentric, prospective, double blind study of diagnostic tests on asymptomatic average-risk individuals submitted to screening colonoscopy. Two stool samples were collected and the fecal hemoglobin concentration was determined in the first sample (FIT1) and the highest level of both samples (FITmax) using the OC-sensor™. Areas under the curve (AUC) for CRC and AN were calculated. The best FIT1 and FITmax cut-off values for CRC were determined. At this threshold, number needed to scope (NNS) to detect a CRC and an AN and the cost per lesion detected were calculated. RESULTS: About 779 individuals were included. An AN was found in 97 (12.5%) individuals: a CRC in 5 (0.6%) and an advanced adenoma (≥ 10 mm, villous histology or high grade dysplasia) in 92 (11.9%) subjects. For CRC diagnosis, FIT1 AUC was 0.96 (95%CI: 0.95-0.98) and FITmax AUC was 0.95 (95%CI: 0.93-0.97). For AN, FIT1 and FITmax AUC were similar (0.72, 95%CI: 0.66-0.78 vs 0.73, 95%CI: 0.68-0.79, respectively, P = 0.34). Depending on the number of determinations and the positivity threshold cut-off used sensitivity for AN detection ranged between 28% and 42% and specificity between 91% and 97%. At the best cut-off point for CRC detection (115 ng/mL), the NNS to detect a CRC were 10.2 and 15.8; and the cost per CRC was 1814€ and 2985€ on FIT1 and FITmax strategies respectively. At this threshold the sensitivity, NNS and cost per AN detected were 30%, 1.76, and 306€, in FIT1 strategy, and 36%, 2.26€ and 426€, in FITmax strategy, respectively. CONCLUSION: Performing two tests does not improve diagnostic accuracy, but increases cost and NNS to detect a lesion.

Seguridad y efectividad de los balones gástricos asociados a una dieta hipocalórica en el tratamiento de la obesidad / Safety and effectiveness of gastric balloons associated with hypocaloric diet for the treatment of obesity

Introducción: el balón gástrico produce saciedad precoz favoreciendo la pérdida de peso en un corto plazo de tiempo. El objetivo de este estudio fue evaluar la seguridad y la efectividad del tratamiento mediante balón gástrico y dieta hipocalórica en la obesidad. Material y métodos: estudio de cohortes prospectivo en 91 pacientes obesos sometidos a balón gástrico durante 6 meses. Como criterio de efectividad se consideró el porcentaje de peso perdido (PPP) >= 5 % 6 meses tras su colocación y 6 y 12 meses tras su retirada. Analizamos los resultados por intención de tratar, considerando significativos los valores de p < 0,05. Resultados: empleamos 73 balones rellenos de líquido (80,2 %) y 18 de aire (19,8 %). Tras 6 meses un 73,7 % de pacientes alcanzó el objetivo terapéutico mostrando descenso de peso (13,3 ± 8,8 kg) e IMC (5 ± 3,4 kg/m2) (p < 0,0001), con PPP 11 ± 7 %. Transcurridos 6 y 12 meses de la retirada un 45,1 % y 28,6 % mantenían un PPP >= 5 %. La efectividad a corto y medio plazo se asoció negativamente con obesidad en familiares (p = 0,003 y p = 0,04). La pérdida ponderal lograda tras 6 meses se asoció con efectividad a medio plazo (p = 0,0001). No existió mortalidad, observando 2 desinflados espontáneos y 8 retiradas complicadas, requiriendo cirugía 1 paciente. Los balones rellenos de aire presentaron más complicaciones (p = 0,0005). Conclusiones: la efectividad del tratamiento combinando balón gástrico y dieta hipocalórica en la obesidad disminuye a lo largo del tiempo. Las complicaciones ocurrieron mayoritariamente durante la retirada endoscópica y con el empleo de balones rellenos de aire (AU)

Introduction: intragastric balloons provide early satiety and thereby induce short-term weight loss. The aim of this study was to evaluate safety and short and medium-term effectiveness of gastric balloons associated to hypocaloric diet in obesity. Material and methods: from May 2004 to June 2011 91 obese patients, body mass index [BMI] 45.2 ± 7.2 kg/m2 were prospectively followed after endoscopic implantation of a gastric balloon associated to restricted diet. Successful therapy was defined as percent loss of total weight (%LTW) >= 5 % at six months after balloon placement and 6 and 12 months after their withdrawal. All analyses followed intention-to treat principles considering significant p-values < 0.05. Results: we placed 73 fluid-filled balloons (80.2 %) and 18 air-filled ones (19.8 %). Compared to baseline values, at 6-month 73.7 % subjects succeeded, showing significant reductions in weight (13.3 ± 8.8 kg), BMI (5 ± 3.4 kg/m2) (p < 0.0001), with % LTW 11 ± 7 %. Six and twelve months after retrieval 45.1 % and 28.6 % patients reached % LTW >= 5 %. Short-term and medium-term effectiveness was negatively associated to obesity in first-grade relatives (p = 0.003 and p = 0.04). Higher weight loss 6 months after balloon placement independently predicted medium-term effectiveness (p = 0.0001). Mortality was absent but there were two spontaneous deflations of air-filled balloons and severe withdrawal difficulties in 8 patients, leading to surgery in one case. Retrieval complications associated to air-filled balloons (p = 0.0005). Conclusions: in obesity, effectiveness of gastric balloons associated to hypocaloric diet decreases over time. Complications occurred mainly in the retrieval endoscopic procedure and related to air-filled balloons (AU)

Risk of advanced proximal neoplasms according to distal colorectal findings: comparison of sigmoidoscopy-based strategies.

BACKGROUND: Screening for colorectal cancer with sigmoidoscopy benefits from the fact that distal findings predict the risk of advanced proximal neoplasms (APNs). This study was aimed at comparing the existing strategies of postsigmoidoscopy referral to colonoscopy in terms of accuracy and resources needed. METHODS: Asymptomatic individuals aged 50-69 years were eligible for a randomized controlled trial designed to compare colonoscopy and fecal immunochemical test. Sigmoidoscopy yield was estimated from results obtained in the colonoscopy arm according to three sets of criteria of colonoscopy referral (from those proposed in the UK Flexible Sigmoidoscopy, Screening for COlon REctum [SCORE], and Norwegian Colorectal Cancer Prevention [NORCCAP] trials). Advanced neoplasm detection rate, sensitivity, specificity, and number of individuals needed to refer for colonoscopy to detect one APN were calculated. Logistic regression analysis was performed to identify distal findings associated with APN. All statistical tests were two-sided. RESULTS: APN was found in 255 of 5059 (5.0%) individuals. Fulfillment of UK (6.2%), SCORE (12.0%), and NORCCAP (17.9%) criteria varied statistically significantly (P < .001). The NORCCAP strategy obtained the highest sensitivity for APN detection (36.9%), and the UK approach reached the highest specificity (94.6%). The number of individuals needed to refer for colonoscopy to detect one APN was 6 (95% confidence interval [CI] = 4 to 7), 8 (95% CI = 6 to 9), and 10 (95% CI = 8 to 12) when the UK, SCORE, and NORCCAP criteria were used, respectively. The logistic regression analysis identified distal adenoma ≥10 mm (odds ratio = 3.77; 95% CI = 2.52 to 5.65) as the strongest independent predictor of APN. CONCLUSIONS: Whereas the NORCCAP criteria achieved the highest sensitivity for APN detection, the UK recommendations benefited from the lowest number of individuals needed to refer for colonoscopy.

Safety and effectiveness of gastric balloons associated with hypocaloric diet for the treatment of obesity.

INTRODUCTION: intragastric balloons provide early satiety and thereby induce short-term weight loss. The aim of this study was to evaluate safety and short and medium-term effectiveness of gastric balloons associated to hypocaloric diet in obesity. MATERIAL AND METHODS: from May 2004 to June 2011 91 obese patients, body mass index (BMI) 45.2 +/- 7.2 kg/m2 were prospectively followed after endoscopic implantation of a gastric balloon associated to restricted diet. Successful therapy was defined as percent loss of total weight (%LTW) > or = 5 % at six months after balloon placement and 6 and 12 months after their withdrawal. All analyses followed intention-to treat principles considering significant p-values < 0.05. RESULTS: we placed 73 fluid-filled balloons (80.2 %) and 18 air-filled ones (19.8 %). Compared to baseline values, at 6-month 73.7 % subjects succeeded, showing significant reductions in weight (13.3 +/- 8.8 kg), BMI (5 +/- 3.4 kg/m2) (p < 0.0001), with % LTW 11 +/- 7 %. Six and twelve months after retrieval 45.1 % and 28.6 % patients reached % LTW > or = 5 %. Short-term and medium-term effectiveness was negatively associated to obesity in first-grade relatives (p = 0.003 and p = 0.04). Higher weight loss 6 months after balloon placement independently predicted medium-term effectiveness (p = 0.0001). Mortality was absent but there were two spontaneous deflations of air-filled balloons and severe withdrawal difficulties in 8 patients, leading to surgery in one case. Retrieval complications associated to air-filled balloons (p = 0.0005). CONCLUSIONS: in obesity, effectiveness of gastric balloons associated to hypocaloric diet decreases over time.Complications occurred mainly in the retrieval endoscopic procedure and related to air-filled balloons.