Precursors Of Colorectal Cancer Research Articles

Endoscopic management of colorectal polyps: From benign to malignant polyps.

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer related death in the world. The early detection and removal of CRC precursor lesions has been shown to reduce the incidence of CRC and cancer-related mortality. Endoscopic resection has become the first-line treatment for the removal of most precursor benign colorectal lesions and selected malignant polyps. Detailed lesion assessment is the first critical step in the evaluation and management of colorectal polyps. Polyp size, location and both macro- and micro- features provide important information regarding histological grade and endoscopic resectability. Benign polyps and even malignant polyps with superficial submucosal invasion and favorable histological features can be adequately removed endoscopically. When compared to surgery, endoscopic resection is associated with lower morbidity, mortality, and higher patient quality of life. Conversely, malignant polyps with deep submucosal invasion and/or high risk for lymph node metastasis will require surgery. From a practical standpoint, the most appropriate strategy for each patient will need to be individualized, based not only on polyp- and patient-related characteristics, but also on local resources and expertise availability. In this review, we provide a broad overview and present a potential decision tree algorithm for the evaluation and management of colorectal polyps that can be widely adopted into clinical practice.

Association between body mass index and colorectal adenomas: Findings from a case-control study in Vietnam.

Colorectal cancer is a leading cancer worldwide and in Vietnam. Adenomas (adenomatous polyps) is an important precursor of colorectal cancer. There is currently no study to determine the modifiable risk factors for colorectal adenomas, including body mass index (BMI) in Vietnam. We conducted an individually matched case-control study of 1149 colorectal adenomas and 1145 controls in a large-scale colorectal screening program involving 103 542 individuals aged 40-75 years old in Hanoi, Vietnam. Conditional logistic regression was used to evaluate the association between BMI and colorectal adenomas prevalence, after controlling for potential confounders. Overall, comparing to normal weight (ie, 18.5-22.9kg/m2 ), underweight (ie, BMI < 18.5) was associated with a non-statistically significant increased prevalence of colorectal adenomas (odd ratio [OR]=1.29 and 95% confident interval [CI]: 0.88-1.87). This association became significant among male (OR=1.98, 95% CI: 1.20-3.27), male who were ever smokers (OR=2.59, 95% CI: 1.33-5.03), nonregular exercise (OR=2.44, 95% CI: 1.26-4.73) and individuals with cardiometabolic disorders (OR=3.46, 95% CI: 1.19-10.00). The association between underweight and colorectal adenomas did not vary by smoking status, drinking status, family history of cancer, adenomas types or cardiometabolic disorders. No association was observed among obese individuals (BMI ≥ 25). In the population with low prevalence of obesity, we found that the association between BMI and colorectal adenomas followed a reversed J-shape that underweight was associated with increased prevalence. Further studies are, therefore, warranted to replicate our results and to investigate the biologic mechanism the effect of underweight on colorectal adenomas prevalence.

CME Exam 2: The Sulfur Microbial Diet Is Associated with Increased Risk of Early-Onset Colorectal Cancer Precursors

CME Exam 2: The Sulfur Microbial Diet Is Associated with Increased Risk of Early-Onset Colorectal Cancer Precursors

Clinical yield of screening colonoscopies in Jamaica.

There is still no organised national screening programme for colorectal cancer in Jamaica. We sought to evaluate the detection of colorectal cancer precursor lesions in patients who underwent opportunistic screening over three years. Patients with colorectal polyps were selected for further study. In 431 procedures, there were 84 (19.5%) patients with colorectal polyps identified at screening colonoscopy, which gave a 19.5% sensitivity to identify patients with polyps at risk of developing colorectal cancer, 9.5% being <50 years of age. At the time of examination, 16.7% had already developed invasive adenocarcinoma. We conclude that it is time for policy makers to develop a national colorectal cancer screening programme to diagnose patients early and improve their therapeutic outcomes.

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.

The Sulfur Microbial Diet Is Associated With Increased Risk of Early-Onset Colorectal Cancer Precursors

Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H2S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking. We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses' Health Study II (1991-2015), a prospective cohort study with dietary assessment every 4 years through validated food frequency questionnaires and an assessment of dietary intake during adolescence in 1998. The sulfur microbial diet was characterized by intake high in processed meats, foods previously linked to CRC development, and low in mixed vegetables and legumes. Multivariable logistic regression for clustered data was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). We documented 2911 cases of early-onset adenoma. After adjusting for established risk factors, higher sulfur microbial diet scores were associated with increased risk for early-onset adenomas (ORquartile [Q]4 vs Q1, 1.31; 95% CI, 1.10-1.56, Ptrend= .02), but not serrated lesions. Compared with the lowest, women in the highest quartile of sulfur microbial diet scores had significantly increased risk of early-onset adenomas with greater malignant potential (ORQ4 vs Q1, 1.65 for villous/tubulovillous histology; 95% CI, 1.12-2.43; Ptrend= .04). Similar trends for early-onset adenoma were observed based on diet consumed during adolescence. In contrast, no clear association for adenomas was identified after age50. Our findings in a cohort of young women support a role for dietary interactions with gut sulfur-metabolizing bacteria in early-onset colorectal carcinogenesis, possibly beginning in adolescence.

Total Vitamin D Intake and Risks of Early-Onset Colorectal Cancer and Precursors

Vitamin D has been implicated in colorectal cancer (CRC) pathogenesis, but it remains unknown whether total vitamin D intake is associated with early-onset CRC and precursors diagnosed before age50. We prospectively examined the association between total vitamin D intake and risks of early-onset CRC and precursors among women enrolled in the Nurses' Health Study II. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for early-onset CRC were estimated with Cox proportional hazards model. Multivariable-adjusted odds ratios (ORs) and 95% CIs for early-onset conventional adenoma and serrated polyp were estimated with logistic regression model. We documented 111 incident cases of early-onset CRC during 1,250,560 person-years of follow-up (1991 to 2015). Higher total vitamin D intake was significantly associated with a reduced risk of early-onset CRC (HR for ≥450 IU/day vs <300 IU/day, 0.49; 95% CI, 0.26-0.93; P for trend= .01). The HR per 400 IU/day increase was 0.46 (95% CI, 0.26-0.83). The inverse association was significant and appeared more evident for dietary sources of vitamin D (HR per 400 IU/day increase, 0.34; 95% CI, 0.15-0.79) than supplemental vitamin D (HR per 400 IU/day increase, 0.77; 95% CI, 0.37-1.62). For CRC precursors, the ORs per 400 IU/day increase were 0.76 (95% CI, 0.65-0.88) for conventional adenoma (n= 1,439) and 0.85 (95% CI, 0.75-0.97) for serrated polyp (n= 1,878). In a cohort of younger women, higher total vitamin D intake was associated with decreased risks of early-onset CRC and precursors.

Methylation profile of colon cancer genes in colorectal precursor lesions and tumor tissue: perspectives for screening

Aims Epigenetic alterations of genes involved in colorectal carcinogenesis are likely to be informative biomarkers for early detection. We assessed the methylation profile of a panel of seven colon cancer-related genes comparing normal colon, colorectal cancer (CRC) precursor lesions and cancer tissues from a Brazilian cohort. Methods The cohort comprised 114 CRC patients, including 40 matched normal tissue, 47 patients with adenomas, 33 with serrated polyps and 8 with normal colonic biopsy. DNA methylation status of SEPT9, ALX4, NDRG4, BMP3, APC, p16 and MLH1 was determined by pyrosequencing and correlated with clinicopathological features. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for all genes using cancer endpoint. Results The most frequently methylated genes in cancer and in precancer lesions were SEPT9, ALX4, NDRG4, and BMP3, ranging from 55.3 to 95% of the samples. Overall, the frequency of methylation of these four genes in normal colonic tissue was significantly lower as compared to cancer or precursor lesions both in adenoma–carcinoma (p < .001 and p < .050) and serrated (sessile-serrated lesion) (p < .001 and p < .050) pathways. Additionally, sensitivity for the cancer endpoint ranged from 65.6 to 91.8%, and specificity from 17.9 to 62.9% for SEPT9, ALX4, NDRG4, and BMP3 genes. Moreover, the comethylation of ≥4 genes was higher in sessile-serrated lesion (87.5%) and conventional adenomas (78.7%) than in hyperplastic polyps (43.7%) (p = .025) and was significantly associated with proximal cancers (p = .042). Conclusions Our study suggests the DNA methylation can constitute potential biomarkers in CRC screening of Brazilian population.

Risk Factors of Inadequate Bowel Preparation for Screening Colonoscopy.

The success of a colonoscopy in detecting and removing pre-cancerous and cancerous lesions depends heavily on the quality of bowel preparation. Despite efforts, 20–44% of colonoscopy participants have an inadequate bowel preparation. We aimed to assess and compare risk factors for inadequate bowel preparation and for the presence of advanced colorectal neoplasms in routine screening practice. In this cross-sectional study, among 8125 participants of screening colonoscopy in Germany with a comprehensive assessment of sociodemographic factors, lifestyle and medical history, we examined factors associated with inadequate bowel preparation and with findings of advanced neoplasms using adjusted log-binomial regression models. Among the identified risk factors assessed, three factors were identified that were significantly associated with inadequate bowel preparation: age ≥ 70 years (adjusted prevalence ratios, aPR, 1.50 95%CI 1.31–1.71), smoking (aPR 1.29 95%CI 1.11–1.50) and abdominal symptoms (aPR 1.14 95%CI 1.02–1.27). The same risk factors were also associated with the prevalence of advanced neoplasms in our study (aPR 1.72, 1.62 and 1.44, respectively). The risk factors associated with inadequate bowel preparation in this study were also associated with a higher risk for advanced neoplasms. Inadequate bowel preparation for colonoscopy might lead to missed colorectal cancer (CRC) precursors and the late diagnosis of CRC. People at high risk of advanced neoplasms are in particular need of enhanced bowel preparation.

Dairy Consumption and Risk of Conventional and Serrated Precursors of Colorectal Cancer: A Systematic Review and Meta-Analysis of Observational Studies.

Objective The consumption of dairy is associated with decreased risk of colorectal cancer (CRC), but few studies have assessed the relationship between dairy consumption and precursors of CRC. Therefore, we performed the first meta-analysis to further evaluate this association. Methods PubMed, Embase, Scopus, and Web of Science databases were searched through July 2020 for observational studies. Study-specific risk estimates for the highest versus lowest category were pooled using the random-effects and fixed-effects model. The methodological quality of included studies was assessed using the ROBINS-I Scale. Results A total of 12 studies were included (3 cohort studies and 9 case-control studies). Compared with the lowest level consumption, fermented dairy products had a decreased risk of precursors of CRC in both cohort (RR = 0.92 95% CI: 0.87–0.97) and case-control studies (RR = 0.98 95% CI: 0.96–0.99). Total dairy (RR = 0.80 95% CI: 0.68–0.96) and cheese (RR = 0.96 95% CI: 0.93–0.99) consumption was inversely associated with the risk in case-control studies whereas yogurt consumption was inversely associated with the risk in cohort studies (RR = 0.91 95%CI: 0.86–0.96). No significant associations were found for consumption of total milk and non/low-fat milk. For dose-response analyses, evidence of linear association was found in total dairy and yogurt consumption. The risk decreased by 12% for an increment of 200 g/d total dairy consumption (RR = 0.88 95% CI: 0.81–0.95) and decreased by 8% for an increment of 50 g/d yogurt consumption (RR = 0.92 95% CI: 0.85–0.99). Conclusions Fermented dairy products, specifically yogurt and cheese, were significantly associated with decreased risk of conventional and serrated precursors of colorectal cancer.

ID: 3521647 EFFECT OF CLIP CLOSURE ON OUTCOMES AFTER RESECTION OF LARGE SERRATED POLYPS: RESULTS FROM A RANDOMIZED TRIAL

Serrated polyps, particularly sessile serrated lesions (SSL), are important colorectal cancer precursors. Endoscopic management of serrated polyps often differs from that of adenomatous polyps due to morphology and other specific endoscopic features. SSLs are most commonly located in the proximal colon, where post-polypectomy bleeding rates are higher. There is limited clinical trial evidence to guide best practices for resection of large serrated polyps.

Simple Sugar and Sugar-Sweetened Beverage Intake During Adolescence and Risk of Colorectal Cancer Precursors

Recent increasing trends in early-onset colorectal cancer (CRC) strongly supports that early-life diet is involved in CRC development. However, data are lacking on the relationship with high sugar intake during early life. We prospectively investigated the association of adolescent simple sugar (fructose, glucose, added sugar, total sugar) and sugar-sweetened beverage (SSB) intake with CRC precursor risk in 33,106 participants of the Nurses' Health Study II who provided adolescent dietary information in 1998 and subsequently underwent lower gastrointestinal endoscopy between 1999 and 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression for clustered data. During follow-up, 2909 conventional adenomas (758 high-risk) and 2355 serrated lesions were identified (mean age at diagnoses, 52.2 ± 4.3 years). High sugar and SSB intake during adolescence was positively associated with risk of adenoma, but not serrated lesions. Per each increment of 5% of calories from total fructose intake, multivariable ORs were 1.17 (95% CI, 1.05-1.31) for total and 1.30 (95% CI, 1.06-1.60) for high-risk adenoma. By subsite, ORs were 1.12 (95% CI, 0.96-1.30) for proximal, 1.24 (95% CI, 1.05-1.47) for distal, and 1.43 (95% CI, 1.10-1.86) for rectal adenoma. Per 1 serving/day increment in SSB intake, ORs were 1.11 (95% CI, 1.02-1.20) for total and 1.30 (95% CI, 1.08-1.55) for rectal adenoma. Contrary to adolescent intake, sugar and SSB intake during adulthood was not associated with adenoma risk. High intake of simple sugars and SSBs during adolescence was associated with increased risk of conventional adenoma, especially rectal adenoma.

Evaluation of blue laser endoscopy for detecting colorectal non-pedunculated adenoma

Background and Study AimsNon-pedunculated lesions are easily missed on endoscopy, and histopathological examination shows that some of these lesions are adenomas. Adenoma is a precursor of colorectal cancer, a common tumor of the digestive tract. This study was conducted to compare the detection efficacy of non-pedunculated lesions in the same patient under different modes of blue laser endoscopy and to determine whether the surface pattern of the sample was consistent with its histopathological results. Patients and MethodsA total of 91 patients with non-pedunculated lesions diagnosed at our hospital between April 2018 and March 2019 were included in this study. White light imaging (WLI), linked color imaging (LCI), and blue laser imaging (BLI) modes were used to record the location, number, and Hiroshima classification of the surface patterns of the non-pedunculated lesions. The lesions were removed by different endoscopic excision methods for histopathological examination; the histopathological results were compared with the surface patterns. ResultsA total of 105, 198, and 223 lesions were detected using the WLI, BLI, and LCI modes, respectively. The Wilcoxon signed rank test revealed a significant difference in the number of lesions detected using each observation mode (p < 0.01). The non-pedunculated lesions were primarily located in the rectum and transverse colon, followed by the sigmoid, descending, and ascending colon. The efficacy of LCI and BLI modes was better than that of WLI mode for detecting the non-pedunculated lesions measuring < 5 mm in size (p < 0.05). The surface pattern was not detected by the WLI mode. The surface patterns detected using the LCI and BLI modes were primarily types A and B. Histopathological results of the non-pedunculated lesions included inflammatory polyp, hyperplastic polyp, tubular adenoma, and adenoma. Surface patterns could not be detected using the WLI mode. The McNemar’s test revealed a significant difference between the WLI mode findings and the histopathological results (p < 0.01). No significant difference was observed between the histopathological results and the surface patterns detected using the LCI mode (kappa = 0.57); the agreement was poor. There was also no significant difference between the histopathological results and the surface patterns detected using the BLI mode (kappa test, p < 0.01; kappa = 0.88); hence, there was good agreement between the surface patterns detected using the BLI mode and the histopathological results. ConclusionThe detection rate of colorectal non-pedunculated lesions may be improved using blue laser endoscopy. Non-pedunculated colorectal adenomas could be identified more accurately using the BLI mode, which might improve the adenoma detection rate, thus indicating that BLI is a feasible option in the practical settings.

Methylation Status of miR-200b Promoter in Colorectal Polyp and Adenocarcinoma Tissues

Background: Aberrant DNA methylation is a common molecular feature in colorectal cancer (CRC). Hypermethylation of miR-200b promoter, as an epigenetic factor, is involved in CRC tumorigenesis. The methylation status of miR-200b has been examined in CRC and adjacent normal tissues. Objectives: This study aimed to investigate miR-200b methylation in a series of colorectal adenomatous polyps, hyperplastic polyps, and adenocarcinoma tissues as precursors of CRC in the Iranian population for the first time. Materials and Methods: In this cross-sectional study (2017-2018), the methylation status of the miR-200b promoter was investigated using methylation-specific PCR in 131 fresh samples, including 30 adenocarcinoma specimens, 17 tumor-adjacent normal tissues, 78 primary lesions (55 adenomatous polyps and 23 hyperplastic polyps) and 6 healthy individuals. Results: Methylation of miR-200b was detected in adenocarcinoma samples (86%) and adenomatous polyps (85%); however, most of the hyperplastic polyps were unmethylated (69.6%). Neither control individuals nor tumor-adjacent normal tissues exhibited methylation in the miR-200b promoter. Aberrant methylation of miR-200b was significantly more common in tumor tissues and adenomatous polyps than in hyperplastic polyps (P&lt;0.0001) and tumor-adjacent normal samples (P&lt;0.0001). Conclusion: Methylation status of the miR-200b promoter was significantly altered during CRC development and may be identified as an attractive biomarker for the early detection of the disease.

Network Pharmacology and Molecular Docking on the Molecular Mechanism of Luo-hua-zi-zhu (LHZZ) Granule in the Prevention and Treatment of Bowel Precancerous Lesions.

The Luo-hua-zi-zhu (LHZZ) granule has been widely used for the treatment of colorectal adenoma (CRA), which is a precursor of colorectal cancer (CRC). However, the active components of LUZZ and its mechanism of action against CRA have not yet been elucidated. This study was designed to investigate the effect of LHZZ on CRA and explore its pharmacological mechanisms. First, a total of 24 chemical constituents were identified in the 50% aqueous methanol extract of LHZZ granule based on the mass fragment patterns and mass spectral library using the high resolution UPLC-Q-TOF MS/MS system. Subsequently, based on a network pharmacology study, 16 bioactive compounds and 28 targets of the LHZZ associated with CRA were obtained, forming a compound-target network. Molecular docking tests showed tight docking of these compounds with predicted targeted proteins. The protein–protein interaction (PPI) network identified AKT1, CASP3, TP53 and EGFR as hub targets. The Kyoto Encyclopedia of Genes and Genomes pathway network and pathway-target-compound network revealed that the apoptosis pathway was enriched by multiple signaling pathways and multiple targets, including the hub targets. Finally, the reliability of the core targets was evaluated using molecular docking technology and in vitro studies. Our study indicated that the LHZZ particle has preventive and treatment effect on colorectal adenoma through multi-component, multi-target and multi-pathway.

Phosphodiesterase 5 Inhibitor Use and Risk of Conventional and Serrated Precursors of Colorectal Cancer.

Phosphodiesterase 5 (PDE5) inhibitors have been hypothesized to have chemoprotective effects in colorectal cancer. Current population-based epidemiologic evidence is, however, limited and inconsistent. Among 18,123 men in the Health Professionals Follow-up Study who had at least one lower gastrointestinal endoscopy, we evaluated the association between PDE5 inhibitor use and risk of conventional adenoma and serrated lesion between 2000 and 2010, adjusted for repeated observations and multiple risk factors. We stratified by erectile dysfunction to account for potential "confounding by indication." We documented 2,595 conventional adenomas and 1,395 serrated lesion polyps during the follow-up period. Using people without erectile dysfunction as reference group, recent PDE5 inhibitor use at baseline was not associated with lower risk of conventional adenoma [erectile dysfunction with PDE5 inhibitors: OR = 1.08; 95% confidence interval (CI) = 0.92-1.26; erectile dysfunction without PDE5 inhibitors: OR = 0.95; 95% CI, 0.85-1.06], serrated lesions (erectile dysfunction with PDE5 inhibitors: OR = 1.19; 95% CI = 0.97-1.45; erectile dysfunction without PDE5 inhibitors: OR = 1.03; 95% CI = 0.89-1.19), or advanced conventional adenomas (erectile dysfunction with PDE5 inhibitors: OR = 1.20; 95% CI = 0.94-1.53; erectile dysfunction without PDE5 inhibitors: OR = 0.95; 95% CI = 0.79-1.14). No association was found for PDE5 inhibitor use ever before as well. We found no evidence of an association between PDE5 inhibitor use and risk of conventional and serrated precursors of colorectal cancer. We show that PDE5 inhibitor use is not associated with precursors of colorectal cancer adjusted for medical and lifestyle risk factors among a large population of men with 10 years of follow-up.

Plasma sex hormones and risk of conventional and serrated precursors of colorectal cancer in postmenopausal women

BackgroundSex hormones have been suggested to play a role in colorectal cancer (CRC), but their influence on early initiation of CRC remains unknown.MethodsWe retrospectively examined the associations with risk of CRC precursors, including conventional adenomas and serrated polyps, for plasma estrone, estradiol, free estradiol, testosterone, free testosterone, sex hormone-binding globulin (SHBG), and the ratio of estradiol to testosterone among 5404 postmenopausal women from the Nurses’ Health Study I and II. Multivariable logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI). Given multiple testing, P < 0.005 was considered statistically significant.ResultsDuring 20 years of follow-up, we documented 535 conventional adenoma cases and 402 serrated polyp cases. Higher concentrations of SHBG were associated with lower risk of conventional adenomas, particularly advanced adenomas (multivariable OR comparing the highest to the lowest quartile, 0.40, 95% CI 0.24–0.67, P for trend < 0.0001). A nominally significant association was found for SHBG with lower risk of large serrated polyps (≥ 10 mm) (OR, 0.47, 95% CI 0.17–1.35, P for trend = 0.02) as well as free estradiol and free testosterone with higher risk of conventional adenomas (OR, 1.54, 95% CI 1.02–2.31, P for trend = 0.03 and OR, 1.33, 95% CI 0.99–1.78, P for trend = 0.03, respectively).ConclusionsThe findings suggest a potential role of sex hormones, particularly SHBG, in early colorectal carcinogenesis.

An \u201cexpressionistic\u201d look at serrated precancerous colorectal lesions

BackgroundApproximately 60% of colorectal cancer (CRC) precursor lesions are the genuinely-dysplastic conventional adenomas (cADNs). The others include hyperplastic polyps (HPs), sessile serrated lesions (SSL), and traditional serrated adenomas (TSAs), subtypes of a class of lesions collectively referred to as “serrated.” Endoscopic and histologic differentiation between cADNs and serrated lesions, and between serrated lesion subtypes can be difficult.MethodsWe used in situ hybridization to verify the expression patterns in CRC precursors of 21 RNA molecules that appear to be promising differentiation markers on the basis of previous RNA sequencing studies.ResultsSSLs could be clearly differentiated from cADNs by the expression patterns of 9 of the 12 RNAs tested for this purpose (VSIG1, ANXA10, ACHE, SEMG1, AQP5, LINC00520, ZIC5/2, FOXD1, NKD1). Expression patterns of all 9 in HPs were similar to those in SSLs. Nine putatively HP-specific RNAs were also investigated, but none could be confirmed as such: most (e.g., HOXD13 and HOXB13), proved instead to be markers of the normal mucosa in the distal colon and rectum, where most HPs arise. TSAs displayed mixed staining patterns reflecting the presence of serrated and dysplastic glands in the same lesion.ConclusionsUsing a robust in situ hybridization protocol, we identified promising tissue-staining markers that, if validated in larger series of lesions, could facilitate more precise histologic classification of CRC precursors and, consequently, more tailored clinical follow-up of their carriers. Our findings should also fuel functional studies on the pathogenic significance of specific gene expression alterations in the initiation and evolution of CRC precursor subtypes.

The Effect of Smoking on the Number and Type of Rectal Aberrant Crypt Foci (ACF)-First Identifiable Precursors of Colorectal Cancer (CRC).

Background: The problem of smoking and its influence on the occurrence of precursors and advanced colorectal cancer is often discussed in the medical literature. Tobacco smoke can provide a non-nutritional source of polycyclic hydrocarbons and other substances which, when combined with an incorrect diet, may play a role in promoting carcinogenesis at the level of the genetic control mechanism. The aim of our study was to assess the effect of smoking on the frequency and type of aberrant crypt foci (ACF) in the rectum and polyps in the large intestine in people who smoke more than 20 cigarettes a day for more than 20 years. Methods and Findings: A colonoscopy combined with rectal mucosa staining with 0.25% methylene blue was performed in 131 patients. Each of the study participants gave informed consent to participate in the study. Three bioptates were collected from the foci defined macroscopically as ACF; in cases where there were fewer foci, the number of collected foci was respectively lower. On the colonoscopy day, patients completed the questionnaire regarding epidemiological data used for analysis of factors affecting the occurrence of ACF in the study group. The number of ACF in the colon was divided into three groups: −ACF < 5, 5 < ACF < 10, ACF > 10. In the statistical analysis, numerical data were presented and real numbers, range of arrhythmic means, mean standard deviation, and results of probability distribution. The Student’s test, U test, and chi2 were applied in order to determine the significance of differences of means and frequency of events in both groups. The level of significance was set at α = 0.05. Statistica 7.1 and Excel 2010 were used. Most smokers are in the age groups between 51–70 years. In the youngest (31–40 years), single ACF appear first (ACF <5) ACF in the number of 5–10 appear a little later (around 50 years of age) and dynamically increase, reaching a maximum at the age of 60–65.ACF in the number >10 appear at the latest age (55 years old) and their number gradually increases with age (linear growth). The probability of occurrence of ACF in all groups is greater in smokers, and the difference for the ACF group 5-10 and ACF >10 is statistically significant with a significance level of p < 0.05. Apart from ACF normal, all types of ACF are more likely in this group than in non-smokers and these differences are statistically significant with p < 0.05. Conclusions: Smoking has a significant impact on the number and type of rectal ACF. Smokers have a greater number of ACFs in the rectum than non-smokers, and the most common type is hyperplastic ACF. Smokers are more likely to develop polyps in all sections of the colon compared to non-smokers.

Features associated with high-risk sessile serrated polyps at index and follow-up colonoscopy.

Clinically significant serrated polyps are precursors of colorectal cancers, with features considered high risk including size ≥10mm, dysplasia, and presence of synchronous conventional adenoma. While these features have been described in cohorts undergoing screening colonoscopy, there is little information regarding the prevalence and patient characteristics associated with high-risk sessile serrated polyps (SSPs) in those undergoing surveillance colonoscopy. Polyp pathology at the index and first follow-up colonoscopy performed between 2004 and 2019 were examined in patients enrolled in a surveillance program because of an index finding of adenoma and/or SSP. Demographics and pathology features for SSP were compared between the colonoscopies. Of 6297 patients undergoing index colonoscopy, 2035 underwent follow-up colonoscopy after 3.3years (interquartile range 2.1-4.8years). The proportion with SSP decreased from 7.6% at index to 5.0% at follow-up (P<0.001); however, the proportion of SSPs that were considered high risk was not different between the colonoscopies (62.8% vs 62.4%). Female gender was associated with the presence of high-risk SSP at index colonoscopy (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.28-2.06), while age ≥75years (OR 3.38, 95% CI 1.67-6.81) and previous high-risk SSP (OR 9.40, 95% CI 4.23-20.88) were independently associated with high-risk SSP at follow-up. The prevalence of SSP falls by one-third at first follow-up colonoscopy although the proportion of SSP with high-risk features remains the same. While females were more likely to have a high-risk SSP at the index colonoscopy, those at greatest risk for high-risk SSP at follow-up colonoscopy were age >75years and an index high-risk SSP.