Synchronous Polyps Research Articles

Risk factors for synchronous high-risk polyps in patients with colorectal cancer.

Colorectal cancer (CRC) patients may experience inadequate preoperative colonoscopy due to bowel obstruction or inadequate bowel preparation, leading to potential oversight of other polyps. We aimed to identify risk factors for CRC complicated with synchronous high-risk polyps. A retrospective analysis of 6,674 CRC patients from December 2014 to September 2018 was conducted. High-risk polyps were defined as adenomas or serrated polyps that were ≥10 mm, or with tubulovillous/villous components or high-grade dysplasia. All other polyps were defined as low-risk polyps. Patients with complete pathological and clinical information were categorized into three groups: the no polyp group, the low-risk polyp group, and the high-risk polyp group. Univariate and multivariate logistic regression analyses were performed to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for all potential risk factors. Among the 4,659 eligible patients, 848 (18.2%) were found to have low-risk polyps, while 675 (14.5%) were diagnosed with high-risk polyps. In a multivariate logistic regression model, compared to patients without polyps, those with synchronous high-risk polyps were more likely to be male (OR = 2.07), aged 50 or older (OR = 2.77), have early-stage tumors (OR = 1.46), colon tumors (OR = 1.53), NRAS mutant tumors (OR = 1.66), and BRAF wild-type tumors (OR = 2.43). Our study has identified several risk factors associated with the presence of synchronous high-risk polyps in CRC patients. Based on these findings, we recommend that patients who exhibit these high-risk factors undergo early follow-up of colonoscopy to detect synchronous polyps early.

Risk of advanced neoplasia after removal of colorectal adenomas with high-grade dysplasia

BackgroundMany studies reported the presence of adenomas with high-grade dysplasia (HGD) at index colonoscopy increased the incidence of advanced neoplasia (AN) and colorectal cancer (CRC) following. However, the conclusion remains obscure due to lack of studies on the specific population of adenomas with HGD. This study aimed to assess the long-term risk of AN and CRC after removal of adenomas with HGD.MethodsA total of 814 patients who underwent adenomas with HGD removal between 2010 and 2019 were retrospectively analyzed. The outcomes were the incidences of AN and CRC during surveillance colonoscopy. Cox proportional hazards models were utilized to identify risk factors associated with AN and CRC.ResultsDuring more than 2000 person-years of follow-up, we found that AN and CRC incidence densities were 44.3 and 4.4 per 1000 person-years, respectively. The 10-year cumulative incidence of AN and CRC were 39.1% and 5.5%, respectively. In the multivariate model, synchronous low-risk polyps (HR 1.80, 95% CI 1.10–2.93) and synchronous high-risk polyps (HR 3.99, 95% CI 2.37–6.72) were risk factors for AN, whereas participation in surveillance colonoscopy visits (HR 0.56, 95% CI 0.36–0.88 for 1 visit; HR 0.10, 95% CI 0.06–0.19 for ≥ 2 visits) were associated with decreased AN incidence. Additionally, elevated baseline carcinoembryonic antigen (CEA) level (HR 10.19, 95% CI 1.77–58.59) was a risk factor for CRC, while participation in ≥ 2 surveillance colonoscopy visits (HR 0.11, 95% CI 0.02–0.56) were associated with decreased CRC incidence. Interestingly, for 11 patients who developed CRC after removal of adenomas with HGD, immunohistochemistry revealed that 8 cases (73%) were deficient mismatch repair CRCs.ConclusionsPatients who have undergone adenoma with HGD removal are at higher risk of developing AN and CRC, while surveillance colonoscopy can reduce the risk. Patients with synchronous polyps, or with elevated baseline CEA level are considered high-risk populations and require more frequent surveillance.

Assessment of Patient Referrals with Large Numbers of Non-pedunculated Colorectal Lesions

Background: Large (≥20mm) non-pedunculated colorectal lesions are frequently referred to specialty centers for endoscopic resection. These lesions are technically challenging to resectand associated with substantially greater risk than smaller lesions. Patients with such polypsoften have synchronous lesions. We sought to identify evidence for whether synchronouslesions were sometimes the true basis for referral of large non-pedunculated colorectal polypsfrom community endoscopists to a tertiary center.
 Methods: We utilized a prospectively collected database of 1356 consecutive referred patients to an expert colonoscopist at our tertiary center between August 2019 and May 2023. We identified patients with ≥30 precancerous lesions resected from the colorectum during their first two colonoscopies at our center. Patients in the database with the same gender, within 3 yearsof age, and with the same location (proximal vs. distal colon) of the index large lesion referred for resection were identified as controls. Groups were compared for the size of index lesion, number of polyps resected by both centers, and size of polyps resected.
 Results: Among 1356 patients, 49 (3.6%) had ≥30 precancerous lesions resected at our center. Compared to controls, the index lesion was smaller in patients with ≥30 lesions (mean 28.9mmvs 23.3mm). Among patients with ≥30 synchronous polyps, the referring physician resected 10.6% of all synchronous lesions, compared to 47.8% in the control group (p<0.0001). Inpatients with ≥30 lesions, 84% of all synchronous lesions were <10mm, 15% were 10-19mm, and only 1% were >20mm.
 Conclusion: Our results suggest a subset of patients with large non-pedunculated colorectal precancerous lesions referred to tertiary centers are referred because of the number of lesions present, rather than technical challenges associated with resection of individual lesions. The rationale for these referrals is uncertain. It may lie in the reimbursement system, which only compensates physicians for the first polypectomy.

Risk of total metachronous advanced neoplasia at surveillance colonoscopy after detection of serrated lesions: a matched case-cohort study.

BACKGROUND : Serrated lesions are potential colorectal cancer precursors. This study evaluated the presence of total metachronous advanced neoplasia (T-MAN) at follow-up in patients with index serrated lesions compared with a matched cohort without serrated lesions. METHODS : Patients aged 45-74 years with serrated lesions were matched 2:1 by sex, age, synchronous polyps, and timing of index colonoscopy, to patients without serrated lesions. The primary outcome was T-MAN (advanced adenoma or high-risk serrated lesion) at follow-up. Secondary outcomes included presence of T-MAN stratified by synchronous polyps and serrated lesion characteristics. RESULTS : 1425 patients were included (475 patients, 642 serrated lesions; 950 controls; median follow-up 2.9 versus 3.6 years). Patients with serrated lesions had greater risk of T-MAN than those without (hazard ratio [HR] 6.1, 95 %CI 3.9-9.6). Patients with serrated lesions and high-risk adenoma (HRA) had higher risk of T-MAN than those with HRA alone (HR 2.6, 95 %CI 1.4-4.7); similarly, patients with serrated lesions plus low-risk adenoma (LRA) had higher risk than those with LRA alone (HR 7.0, 95 %CI 2.8-18.4), as did patients with serrated lesions without adenoma compared with no adenoma (HR 14.9, 95 %CI 6.5-34.0). Presence of proximal sessile serrated lesion (SSL; HR 9.3, 95 %CI 5.4-15.9), large SSL (HR 17.8, 95 %CI 7.4-43.3), and proximal large SSL (HR 25.0, 95 %CI 8.8-71.3), but not distal SSL, were associated with greater risk for T-MAN. CONCLUSION : Patients with serrated lesions had higher risk for T-MAN regardless of synchronous adenomas. Patients with serrated lesions and HRA, and those with large or proximal SSLs, were at greatest risk.

A232 RISK OF TOTAL METACHRONOUS ADVANCED NEOPLASIA AT SURVEILLANCE COLONOSCOPY AFTER DETECTION OF SERRATED LESIONS: A MATCHED COHORT STUDY

Abstract Background Serrated lesions (SLs), including sessile serrated lesions (SSL) and traditional serrated adenomas (TSA) have become subject of increased interest for their role as CRC precursors. Purpose Study aim was to evaluate the risk to develop total metachronous advanced neoplasia (T-MAN) at follow-up in patients with index SL compared to a matched cohort without SL. Method Patients 45-74y with SLs were identified through pathology database search. SL patients were matched 2:1 by sex; age; synchronous polyps (high-risk adenoma [HRA], low-risk adenoma [LRA], no-adenoma); timing of index, to patients without SL. Primary outcome was risk of T-MAN (advanced adenoma or high-risk SL) at follow-up. Secondary outcomes included risk of T-MAN stratified by synchronous polyps and SL characteristics. Result(s) 1425 patients were included (475 patients, 642 SLs; 950 controls (mean follow-up 2.9 vs 3.9y). The SL group had greater risk of T-MAN compared to the non-SL group [Hazard-ratio (HR)=6.12 (95%confidence-interval (CI)3.91-9.58)]. Patients with SL+HRA had higher risk of T-MAN compared to HRA alone [HR=2.62 (95%CI 1.45-4.71)], as well as patients with SL+LRA compared to LRA alone [HR=7.03 (95%CI 2.78-18.44)], and SL without adenoma compared to no-adenoma [HR=14.87 (95%CI 6.51-33.95)]. Presence of proximal SSL (HR=9.30), large SSL (HR=17.87) and proximal large SSL (HR=24.99), but not distal SSL, was associated with greater risk for T-MAN. Conclusion(s) Patients with SLs are at greater risk for developing T-MAN regardless of synchronous adenomas. Patients with SL and HRA, and those with large or proximal SSLs appear to be at greatest risk for T-MAN. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; ACG Disclosure of Interest R. Djinbachian Grant / Research support from: Grant from the American College of Gastroenterology for the conduction of this project, M.-L. Lafontaine: None Declared, J. Anderson: None Declared, H. Pohl: None Declared, T. Dufault: None Declared, M. Boivin: None Declared, M. Bouin: None Declared, D. von Renteln Grant / Research support from: Daniel von Renteln is supported by a “Fonds de Recherche du Québec Santé” (FRQS) career development award and has received research funding from ERBE, Ventage, Pendopharm, Fujifilm, and Pentax., Consultant of: Boston Scientific and Pendopharm,

Prevalence of synchronous neoplasia in patients with large pedunculated colorectal polyps.

Large (≥ 20 mm) nonpedunculated colorectal lesions have high rates of synchronous neoplasia and advanced neoplasia. Synchronous neoplasia prevalence in patients with large pedunculated lesions is uncertain. We describe synchronous neoplasia in patients with large pedunculated colorectal polyps, using a cohort of patients with large nonpedunculated lesions as controls. This study was a retrospective assessment of a prospectively recorded database listing synchronous findings in patients with ≥ 20 mm colorectal lesions referred to a tertiary center for endoscopic resection. At least one synchronous precancerous lesion was identified in 66/78 patients with large pedunculated index lesions (84.6 %, 95 %CI 74.9-91.1) and 726/814 patients with large nonpedunculated index lesions (89.2 %, 95 %CI 87.1-91.3). Patients with a large pedunculated index lesion had mean of 4.8 synchronous conventional adenomas, 56.4 % had ≥ 1 synchronous high risk lesion (advanced adenoma or advanced serrated lesion), 48.7 % had ≥ 1 synchronous advanced conventional adenoma, and 19.2 % had a synchronous neoplastic lesion ≥ 20 mm. Compared with patients with nonpedunculated index lesions, patients with large pedunculated index lesions had comparable rates of synchronous polyps, adenomas, and sessile serrated lesions, and higher rates of synchronous adenomas with villous elements (15.6 % [95 %CI 13.3-18.3] vs. 26.9 % [95 %CI 18.3-37.7]; P = 0.01) and synchronous pedunculated polyps (9.5 % [95 %CI 7.6-11.7] vs. 33.3 % [95 %CI 23.8-44.4]; P < 0.001). In patients with large (≥ 20 mm) pedunculated colorectal lesions, rates of synchronous neoplasia and advanced synchronous neoplasia were high and comparable to or higher than rates of synchronous neoplasia in patients with large nonpedunculated colorectal lesions.

Clinical, pathological genetics and intratumoral immune milieu of serrated adenocarcinoma of the colon.

Serrated adenocarcinoma (SAC), a recognised WHO variant of colonic adenocarcinoma, is the purported end-product of serrated neoplasia. However, the diagnosis of SAC is infrequently rendered, and little is known about its prognosis, immune microenvironment and molecular alterations. We assessed 903 consecutive colon carcinomas and recognised tumours with ≥ 5% (n = 77) serrated and ≥ 50% serrated patterns (n = 13). We assessed precursor polyps and synchronous polyps. We recorded demographic/clinical parameters, histological features and mismatch repair (MMR) status. We performed immunohistochemistry and quantification on tissue microarray for HLA class I/II proteins, B2MG, CD8, CD163, LAG3, FoxP3, PD-L1 and BRAF V600E. We identified ≥ 5% epithelial serration prevalence in 8.5% of cases and ≥ 50% epithelial serration prevalence in 1.4% of cases. Precursor lesions were present in 21.4% of cases; these were mostly tubular adenomas with two traditional serrated adenomas identified. SAC with ≥ 5% serrations exhibited lower numbers of CD8-positive lymphocytes (P = 0.002) and lower B2MG expression (P = 0.048), although neither value was significant at ≥ 50% serration threshold. There was no difference in HLA class I/II, or PD-L1 expression on tumour cells and no difference in PD-L1, LAG3, FoxP3 and CD163 expression on immune cells. There was no association with MMR status, or BRAFV600E relative to conventional adenocarcinoma. There was improved disease-specific survival on univariate (but not multivariate) analysis between carcinomas with serrated pattern and non-mucinous conventional colonic carcinomas at ≥ 5% epithelial serrations (P = 0.04). SAC category shows a limited impact on survival, and this phenotype may harbour a unique immunological milieu.

An end-to-end tracking method for polyp detectors in colonoscopy videos

Deep learning based computer-aided diagnosis technology demonstrates an encouraging performance in aspect of polyp lesion detection on reducing the miss rate of polyps during colonoscopies. However, to date, few studies have been conducted for tracking polyps that have been detected in colonoscopy videos, which is an essential and intuitive issue in clinical intelligent video analysis task (e.g. lesion counting, lesion retrieval, report generation). In the paradigm of conventional tracking-by-detection system, detection task for lesion localization is separated from the tracking task for cropped lesions re-identification. In the multi object tracking problem, each target is supposed to be tracked by invoking a tracker after the detector, which introduces multiple inferences and leads to external resource and time consumption. To tackle these problems, we proposed a plug-in module named instance tracking head (ITH) for synchronous polyp detection and tracking, which can be simply inserted into object detection frameworks. It embeds a feature-based polyp tracking procedure into the detector frameworks to achieve multi-task model training. ITH and detection head share the model backbone for low level feature extraction, and then low level feature flows into the separate branches for task-driven model training. For feature maps from the same receptive field, the region of interest head assigns these features to the detection head and the ITH, respectively, and outputs the object category, bounding box coordinates, and instance feature embedding simultaneously for each specific polyp target. We also proposed a method based on similarity metric learning. The method makes full use of the prior boxes in the object detector to provide richer and denser instance training pairs, to improve the performance of the model evaluation on the tracking task. Compared with advanced tracking-by-detection paradigm methods, detectors with proposed ITH can obtain comparative tracking performance but approximate 30% faster speed. Optimized model based on Scaled-YOLOv4 detector with ITH illustrates good trade-off between detection (mAP 91.70%) and tracking (MOTA 92.50% and Rank-1 Acc 88.31%) task at the frame rate of 66 FPS. The proposed structure demonstrates the potential to aid clinicians in real-time detection with online tracking or offline retargeting of polyp instances during colonoscopies.

Genetic Obesity Variants and Risk of Conventional Adenomas and Serrated Polyps.

Higher body mass index (BMI) is associated with increased risk of colorectal cancer. How genetically predicted BMI may be associated with colorectal cancer precursors is unknown. Our objective was to quantify the association of genetically predicted and measured BMI with risk of colorectal cancer precursors. We evaluated the association of genetically predicted and measured BMI with risk of conventional adenomas, serrated polyps, and synchronous polyps among 27,426 participants who had undergone at least one lower gastrointestinal endoscopy in the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study. Genetic risk score was derived from 97 BMI-related single nucleotide polymorphisms. Multivariable logistic regression evaluated each polyp subtype compared to non-polyps. For conventional adenomas, the OR per 2-kg/m2 increase was 1.03 (95% CI, 1.01-1.04) for measured BMI and 0.98 (95% CI, 0.88-1.10) for genetically predicted BMI; for serrated polyps, the OR was 1.06 (95% CI, 1.04-1.08) and 1.04 (95% CI, 0.90-1.20), respectively; for synchronous polyps, the OR was 1.10 (95% CI, 1.07-1.13) and 1.09 (95% CI, 0.89-1.34), respectively. Genetically predicted BMI was associated with synchronous polyps in women (OR = 1.37, 95% CI: 1.05-1.79). Genetically predicted BMI was not associated with colorectal cancer precursor lesions. The confidence intervals were wide and encompassed those for measured BMI, indicating that null findings may be due to insufficient power.

Rectal aberrant crypt foci (ACF) as a predictor of benign and malignant neoplastic lesions in the large intestine

BackgroundThe importance of ACF is not fully explained, however, their number may be a good predictor of synchronous and metachronic adenoma or other polyps whose removal reduces the risk of CRC. Due to the epidemiological and genetic association of ACF with pre-cancer lesions, they may be a potential CRC biomarker. The aim of our study was to show that the number and type of rectal ACF may be a good predictive factor for the presence of polyps located proximally from the splenic flexure and that the type and number of ACF can correlate with the number and specific types of polyps in the large intestine.MethodsThe study included 131 patients who underwent colonoscopy combined with rectal mucosa staining with 0.25% methylene blue. The number of rectal ACF was determined and bioptats were sampled for histopathological examination to assess the type of ACF. Endoscopic ACF assessment criteria given by L. Roncucci were used. The obtained material was subjected to statistical analysis using probability distribution, U-test, t-student test, and chi 2 as well as the Statistica 7.1 software package.ResultsThe study population was divided into three subgroups according to the number of ACF observed, i.e. ACF < 5, 5–10 and > 10. ACF < 5 were found in 35 patients (29.41%), 5–10 ACF in 70 (58.82%) and ACF > 10 in 14 individuals (11.76%).The study revealed the presence of normal ACF (p = 0.49), hyperplastic ACF (p = 0.34), dysplastic ACF (p = 0.11), and mixed ACF (p = 0.06). A single type of ACF was most commonly observed (n = 88, p = 0.74). In the researched group a larger number of ACF is concurrent with adenomas and hyperplastic polyps. The number of ACF clearly correlates with the dysplasia advancement in the adenoma and the number of polyps found.ConclusionsRectal ACF are a useful marker for the presence of cancerous lesions in the proximal and distal sections of the large intestine.

Characterization of Mucosal Dysbiosis of Early Colonic Neoplasia.

Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesions in the colon that can be detected by high-definition chromoendoscopy with contrast dye spray. Although frequently associated with synchronous adenomas, their role in colorectal tumor development, particularly in the proximal colon, is still not clear. The goal of this study was to evaluate the profile of colon-adherent bacteria associated with proximal ACF and to investigate their relationship to the presence and subtype of synchronous polyps present throughout the colon. Forty-five subjects undergoing a screening or surveillance colonoscopy were included in this retrospective study. Bacterial cells adherent to the epithelia of ACF and normal mucosal biopsies were visualized by in situ hybridization within confocal tissue sections. ACF showed significantly greater heterogeneity in their bacterial microbiome profiles compared with normal mucosa. One of the bacterial community structures we characterized was strongly correlated with the presence of synchronous polyps. Finally, using DNA mass spectrometry to evaluate a panel of colorectal cancer hotspot mutations present in the ACF, we found that three APC gene mutations were positively associated with the presence of Instestinibacter sp., whereas KRAS mutations were positively correlated with Ruminococcus gnavus. This result indicates a potential relationship between specific colon-associated bacterial species and somatically acquired CRC-related mutations. Overall, our findings suggest that perturbations to the normal adherent mucosal flora may constitute a risk factor for early neoplasia, demonstrating the potential impact of mucosal dysbiosis on the tissue microenvironment and behavior of ACF that may facilitate their progression towards more advanced forms of neoplasia.

Quality of Preoperative Colonoscopy Affects Missed Postoperative Adenoma Detection in Colorectal Cancer Patients.

Despite thorough preoperative screening, 19-30% of synchronous polyps or adenomas are detected after colon cancer surgery. Remnant synchronous lesions require additional colonoscopy procedures or surgery. To investigate factors of preoperative colonoscopy potentially affecting the detection of missed lesions in patients subjected to colorectal cancer surgery. Of 1147 colorectal cancer patients subjected to curative open or laparoscopic colectomy and colonoscopy at the Chungnam National University Hospital from January 2012 to December 2016, 518 patients underwent pre- and postoperative colonoscopy. The index colonoscopy was defined as the last preoperative endoscopy performed. We analyzed pre- and postoperative medical charts for colonoscopy and pathological data. The effects of patient, procedure, and tumor factors on the postoperative adenoma detection rate, advanced adenoma detection rate, and adenoma miss rate (AMR) were analyzed. The overall AMR was 25.7% (95% confidence interval, 22.2-29.8%). Comparing optimal and non-optimal bowel preparation groups, the latter had greater postoperative polyp missed rate (PMR), AMR (p < 0.01), and AAMR (p = 0.272). The optimal preparation group allowed identification of more synchronous adenomas than in the fair (OR 5.72) and poor (OR 11.39) preparation groups. On univariate analysis, patient age and left-sided colectomy (p < 0.01) influenced AMR. Multivariate analysis showed that age, preoperative bowel preparation, and left colon resection influenced postoperative AMR. A better quality of index colonoscopy had a positive effect on lowering the detection rate of postoperative adenoma. Older age and suboptimal bowel preparation at the index colonoscopy and left-sided colectomy had negative effects on lowering the postoperative AMR.

Colonic Mucosa With Polypoid Hyperplasia.

Define the morphologic and molecular features of colonic polyps with subtle histologic features. Two hundred specimens were obtained of surveillance colonoscopies. Endoscopic findings were reviewed. Histologic features of the polyps were compared with the flat mucosa. Next-generation sequencing was performed on 30 study polyps and 20 control samples. Polyps with subtle changes comprised 12% of all polyps. All polyps were sessile and small (<0.5 cm) and were located predominantly in the distal colon (60%). Synchronous hyperplastic, sessile serrated, and dysplastic polyps were found in 30%, 7%, and 51% of patients, respectively. A total of 169 (84.5%) polyps showed wide, nonserrated crypts, increased intraluminal mucus, and patent openings. KRAS alterations were present in 30% of polyps. Most polyps with subtle histologic features have recognizable morphologic changes. About one-third harbored KRAS alterations. These polyps should not be regarded as variants of hyperplastic polyps.

French comment on article The clinical significance and synchronous polyp burden of large (≥ 20mm) sessile serrated polyps in patients without serrated polyposis syndrome

French comment on article The clinical significance and synchronous polyp burden of large (≥ 20mm) sessile serrated polyps in patients without serrated polyposis syndrome

Feasibility and Safety of Intraoperative Colonoscopy after Segmental Colectomy and Primary Anastomosis

Patients presenting with near-obstructing colon lesions requiring segmental colectomy may benefit from intraoperative colonoscopy (IOC) after primary anastomosis for a more timely and accurate diagnosis of synchronous lesions. The aim of this study is to demonstrate the feasibility and safety of this technique. A retrospective cohort study of patients undergoing single-stage segmental colectomy and anastomosis at a single tertiary care institution from 2011 to 2013 was performed. One Hundred and sixty-eight consecutive patients underwent segmental colectomy and primary anastomosis of which 78 (46%) were unable to receive preoperative colonoscopy (POC) because of near-obstructing lesions and received IOC after the anastomosis. IOC detected synchronous adenomatous polyps in 24.4 per cent, diverticular disease in 19 per cent, and colitis/proctitis in 2.5 per cent. The IOC group was not significantly different from the POC group with regard to overall morbidity (31% vs 39% P = 0.45), anastomotic leakage (1.3% vs 0%, P = 0.46), or wound infection (5.1% vs 1.1%, P = 0.18). Operation time was 19 minutes longer in the intraoperative group, but overall length of hospital stay was not significantly different (6.4 ± 2.9 days vs 7.3 ± 4.6 days). In patients unable to receive POC because of partial obstruction, IOC after primary anastomosis is both feasible and safe for detecting proximal synchronous lesions.

Synchronous Polyps in Patients with Large Sessile Serrated Polyps Not Meeting SPS Criteria

The World Health Organization (WHO) defines serrated polyposis syndrome (SPS) as presence of at least five serrated polyps located proximally to the

The clinical significance and synchronous polyp burden of large (≥ 20 mm) sessile serrated polyps in patients without serrated polyposis syndrome.

Sessile serrated polyps (SSPs) are important precursors of colorectal carcinoma and interval cancer. Large SSPs (≥ 20 mm) outside the definition of serrated polyposis syndrome (SPS) have not been studied in comparison with SPS. We aimed to describe the characteristics of patients with large SSPs in this context. Patients with at least one SSP (≥ 20 mm) were eligible. Data from three consecutive colonoscopies were used to compare clinical and endoscopic characteristics in three patient groups: SPS, a solitary large SSP, and patients with at least two SSPs without fulfilling the criteria for SPS (oligo-SSP). Data on the diagnostic colonoscopy were collected retrospectively, whereas the remaining data was collected prospectively. 67/146 patients (45.9 %) had SPS, 53/146 (36.3 %) had a solitary SSP, and 26/146 (17.8 %) were categorized as oligo-SSP. Personal (16.4 %, 9.4 %, and 11.5 %, respectively) and family (17.9 %, 17.0 %, and 23.1 %, respectively) history of colorectal carcinoma did not differ significantly between groups. Polyp burden was greater in SPS compared with solitary SSP but was not different from oligo-SSP (advanced adenomas: SPS 32.8 % vs. solitary SSP 9.4 % [P = 0.002] vs. oligo-SSP 34.6 % [P = 0.87]; ≥ 10 conventional adenomas: 11.9 % vs. 0 % [P = 0.01] vs. 3.8 % [P = 0.44], respectively). Dysplasia in large SSPs was frequent in all groups (41.1 % overall). SPS was recognized by referring endoscopists in only 9.0 % of cases. Patients with oligo-SSPs have similar synchronous polyp burden and clinical characteristics as patients with SPS and may require similar surveillance. Modification of the criteria for the diagnosis of SPS to include this group seems warranted. Patients with a solitary SSP have a lower risk of synchronous polyps, including advanced adenomas. Larger studies are warranted to determine whether these patients may return to standard surveillance following complete examination and clearance of the colon.

Acquired somatic TP53 or PIK3CA mutations are potential predictors of when polyps evolve into colorectal cancer.

Colorectal cancer (CRC) develops from accumulated mutations. However, which gene determines the malignant transformation from adenoma to carcinoma is still uncertain. Fifty-three formalin fixed paraffin-embedded polyps that had pathological findings from patients with hyperplasia, adenomatous, and tubular adenoma < 1 cm (non-neoplasia polyps, NNP, n = 27) or tubular adenoma ≥ 1 cm, tubulovillous and villous adenoma (neoplastic polyps, NP, n = 26) were recruited. Six paired synchronous polyps and cancer tissues and 50 independent fresh CRC tumors were also collected. All tissues were analyzed for their mutation genomes using next generation sequencing with a 50-gene panel. There were 40 types of somatic variants found in 7 genes, APC (43%), KRAS (28%), TP53 (11%), FBXW7 (8%), GNAS (4%), SMAD4 (2%), and BRAF (2%), and they were detected in 32 (60%) polyps. If combined with the mutation spectrum found in CRC tissues, a significant increase in the mutation rate in TP53 and PIK3CA from NNP, NP, early and late stage carcinoma (7%, 15%, 33.3% and 65% for TP53, p < 0.001; 0%, 0%, 23.3% and 25% for PIK3CA, p = 0.002) were noticed. Furthermore, distinct molecular features can be found in five pairs of synchronous polyps and tumors. However, TP53 or PIK3CA mutations can be found in tumor tissues but not in polyps. By systematically investigating the genome from polyps to tumor tissues, we demonstrated that acquired TP53 or PIK3CA somatic mutations are potential predictors for malignancy development. These results may aid in the identification of high risk individuals with tissues harboring mutations in these two genes.

Risk factors for metachronous colorectal cancer or polyp: A systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to identify personal, lifestyle, and tumor-related risk factors for metachronous colorectal cancer (CRC) and polyp. Relevant studies were identified by searching MEDLINE, Web of Science and Cochrane Central Register through 15 May 2016. Estimates for associations were summarized using random effects models. Fifty-five studies were included in the review. For individuals who had a CRC resection, having a synchronous polyp was a risk factor for metachronous CRC or polyp (relative risk [RR], 2.04; 95% confidence interval [CI], 1.48-2.82) and having a synchronous CRC (RR, 1.90; 95% CI, 1.25-2.91) and proximally located CRC (RR, 2.12; 95% CI, 1.24-3.64) were risk factors for metachronous CRC. For individuals who had a polypectomy, larger size (RR, 4.26; 95% CI, 2.11-8.57) or severe dysplasia of the initial polyp (RR, 5.15; 95% CI, 2.02-13.14), and having a synchronous polyp (RR, 2.52; 95% CI, 1.35-4.73) were risk factors for metachronous CRC; and a family history of CRC (RR, 1.90; 95% CI, 1.26-2.87), having a synchronous polyp (RR, 2.47; 95% CI, 1.74-3.50) and a larger size (RR, 1.49; 95% CI, 1.03-2.15) and proximal location of the initial polyp (RR, 1.20; 95% CI, 1.02-1.40) were risk factors for metachronous polyp. Meta-regression showed duration of follow-up was not a source of heterogeneity for most associations. There was no evidence that lifestyle factors were associated with metachronous CRC or polyp risk. A comprehensive list of risk factors identified for metachronous CRC or polyp may have important clinical implications.

Attenuated polyposis of the large bowel: a morphologic and molecular approach.

Attenuated polyposis could be defined as a variant of familial adenomatous polyposis (FAP) in which synchronous polyps of the large bowel range between 10 and 99. We analysed all cases of attenuated polyposis observed over the last 30years with the objectives: (A) to classify the disease according to different type and proportion of polyps; (B) To ascertain the contribution of APC and MutYH genes; (C) to discover features which could arise the suspicion of mutations; (D) To obtain indications for management and follow-up. 84 individuals in 82 families were studied. Polyps were classified into four groups as adenoma, hyperplastic, other serrated lesions or others; APC and MutYH mutations were assessed. Mean age at diagnosis was 54±14years in men and 48±13 in women (P=0.005). Polyps were more numerous in women (37±26 vs 29±22). Sixty % of patients underwent bowel resection, mainly for cancer; the remaining were managed through endoscopy. A total of 2586 polyps were detected at diagnostic endoscopy: 2026 (80%) were removed and analysed. Adenomas were diagnosed in 1445 (70%), hyperplastic polyps in 541 (26%), other serrated lesions in 61 (2.9%). Adenomas and hyperplastic lesions were detected in the majority of patients. In 68 patients (81%) in whom studies were executed, APC mutations were found in 8 and MutYH mutations in 10. Genetic variants were more frequent in women (12 vs 6, P=0.039). Taking into consideration the prevalent (>50%) histology and presence of mutations, patients could be subdivided into four groups: (1) APC mutated polyposis (AFAP), when adenomas were >50% and APC mutations detected (no. 8, 10%); (2) MutYH mutated polyposis (MAP), adenomas >50% and biallelic MutYH mutations (no. 10, 12%); (1) attenuated polyposis without detectable mutations, prevalence of adenomas, 48 cases (57%); (1) hyperplastic-serrated polyposis, with prevalence (>50%) of hyperplastic/other serrated lesions and no constitutional mutation (no. 18, 21%). Aggregation of tumors, cancer in probands, distribution of polyps and other clinical characteristics showed no difference among the four groups. In conclusions, AFAP and MAP, the polyposis labeled by constitutional mutations, represented about 25% of all attenuated polyposis. Mutation-associated cases showed an earlier age of onset of polyps and were more frequent in the female sex.