Colorectal Cancer Precursor Lesions Research Articles

Different modifiable risk factors for the development of non-advanced adenoma, advanced adenomatous lesion, and sessile serrated lesions, on screening colonoscopy

The development of premalignant colorectal polyps is significantly influenced by various lifestyle and modifiable risk factors. In our study, we used a large cohort of 9025 patients, who underwent screening colonoscopies at a university hospital, to assess the risk factors associated with the development of three different colorectal cancer precursor lesions: non-advanced adenomas (NAs), advanced adenomatous lesions (ADLs), and sessile serrated lesions (SSLs). Among the participants, 3641 had NAs, 836 had ADLs, and 533 had SSLs. We identified obesity, current smoking, and appendicular skeletal muscle mass as modifiable lifestyle risk factors that increase the development of NAs and ADLs (all P < 0.05). Furthermore, we found a positive correlation between the degree of obesity and an increased risk of developing NAs and ADLs (all P for trend < 0.001), while non-smoking was associated with a decreased risk (P for trend < 0.001 and 0.003, respectively). Smoking was the only modifiable risk factor for developing SSLs (adjusted odds ratio [aOR] 1.58; 95% confidence interval [CI] 1.20–2.07), and the risk was even higher in patients with metabolic syndrome (aOR 1.71; 95% CI 1.05–2.77). Addressing modifiable lifestyle factors such as smoking and obesity could play an important role in reducing the risk of both non-advanced and advanced adenomatous lesions. Smoking cessation is especially important as it is a significant modifiable risk factor for sessile serrated lesions.

Analysis of Immunohistochemical Expression of BRAF (V600E) Mutation in Serrated Colorectal Polyps: A Study from Tertiary Hospital in Oman.

Colorectal cancer (CRC) is considered one of the most common cancers in the world. Serrated polyps were found to be precursor lesions for CRC. BRAF mutation (V600E) has been strongly linked to the development of these lesions. No previous study concerning BRAF immunohistochemical expression in serrated polyps- was done in Oman. The primary objective of our study was to assess the prevalence of BRAF (V600E) mutation in serrated colorectal polyps in the Omani population. The secondary objectives were to assess the prevalence of serrated polyps and their characteristic features: type, site and size as well as the relationship between BRAF (V600E) mutation and polyp type, site and size. Ninety-one hyperplastic polyps (HP) (76.5%), 24 sessile serrated lesions (SSL) (20.2%) and 4 cases of tubular adenomas with low grade dysplasia (3.4%) were studied for BRAF (V600E) immunohistochemical expression. No case of traditional serrated adenoma (TSA) was present. Control cases of craniopharyngioma and papillary thyroid carcinoma were included. BRAF (V600E) IHC was positive in 63 of the HP polyps (69.2%), 13 SSLs (54.2%) and none of the adenomatous polyps. The majority of positive polyps (75.0%) were ≤5 mm in size, 17.9% were 5-10 mm and 7.1% were ≥10 mm in size. The majority of BRAF (V600E) positive polyps (68.1 %) were in the distal colon and 31.9 % were in the proximal colon. The majority of positive cases for BRAF (V600E) were showing multiple polyps (61.8 %). None of the tubular adenomas showed any BRAF (V600E) positivity. Serrated polyps are now well known for their potential to develop CRC. Immunohistochemistry is an easy and reproducible way to detect BRAF (V600E) mutation. Our study showed there is high prevalence (64.3%) of BRAF mutation in serrated polyps in the Omani population. The majority of these polyps- were HP and SSL; and ≤5 mm in size and located in the distal colon.

Non-coding RNAs in Precursor Lesions of Colorectal Cancer: Their Role in Cancer Initiation and Formation.

Colorectal cancer (CRC) is one of the world's most common types of malignancy. The proliferation of precancerous lesions causes this type of cancer. Two distinct pathways for CRC carcinogenesis have been identified: the conventional adenoma-carcinoma pathway and the serrated neoplasia pathway. Recently, evidence has demonstrated the regulatory roles of noncoding RNAs (ncRNAs) in the initiation and progression of precancerous lesions, especially in the adenoma-carcinoma pathway and serrated neoplasia pathway. By expanding the science of molecular genetics and bioinformatics, several studies have identified dysregulated ncRNAs that function as oncogenes or tumor suppressors in cancer initiation and formation by diverse mechanisms via intracellular signaling pathways known to act on tumor cells. However, many of their roles are still unclear. This review summarizes the functions and mechanisms of ncRNAs (such as long non-coding RNAs, microRNAs, long intergenic non-coding RNAs, small interfering RNAs, and circRNAs) in the initiation and formation of precancerous lesions.

Machine learning-based identification of colorectal advanced adenoma using clinical and laboratory data: a phase I exploratory study in accordance with updated World Endoscopy Organization guidelines for noninvasive colorectal cancer screening tests.

The recent World Endoscopy Organization (WEO) guidelines now recognize precursor lesions of colorectal cancer (CRC) as legitimate screening targets. However, an optimal screening method for detecting advanced adenoma (AA), a significant precursor lesion, remains elusive. We employed five machine learning methods, using clinical and laboratory data, to develop and validate a diagnostic model for identifying patients with AA (569 AAs vs. 3228 controls with normal colonoscopy). The best-performing model was selected based on sensitivity and specificity assessments. Its performance in recognizing adenoma-carcinoma sequence was evaluated in line with guidelines, and adjustable thresholds were established. For comparison, the Fecal Occult Blood Test (FOBT) was also selected. The XGBoost model demonstrated superior performance in identifying AA, with a sensitivity of 70.8% and a specificity of 83.4%. It successfully detected 42.7% of non-advanced adenoma (NAA) and 80.1% of CRC. The model-transformed risk assessment scale provided diagnostic performance at different positivity thresholds. Compared to FOBT, the XGBoost model better identified AA and NAA, however, was less effective in CRC. The XGBoost model, compared to FOBT, offers improved accuracy in identifying AA patients. While it may not meet the recommendations of some organizations, it provides value for individuals who are unable to use FOBT for various reasons.

Association between lifestyle and dietary preference factors and conventional adenomas and serrated polyps.

Both conventional adenoma (AD) and serrated polyp (SP) were known precursor lesions of colorectal cancer (CRC). Modifiable lifestyle factors were significantly associated with CRC risk, but whether these factors were related to the risk of different precursors of CRC needed to be clarified. This study aimed to evaluate the risks of AD and SP caused by lifestyle factors and compare the risk differences between AD and SP. The study population was from the CRC screening cohort in Hangzhou, China. A total of 458,457 eligible individuals volunteered to undergo initial screening including the fecal immunochemical test (FIT) and the CRC risk assessment. Finally, 13,993 participants who had undergone colonoscopy tests and had been diagnosed at designated hospitals were selected in this study. All participants were required to fill out a questionnaire during the initial screening for collecting their information. The generalized estimate equation (GEE) model was used to assess the association between lifestyle factors/dietary preferences and AD/SP. The body mass index (BMI) and smoking were positively associated with the risks of only SP (BMI: OR = 1.50, 95%CI: 1.23-1.84; smoking: OR = 1.29, 95%CI: 1.07-1.55), only AD (BMI: OR = 1.53, 95%CI: 1.28-1.82; OR = 1.24, 95%CI: 1.11-1.39), and synchronous SP and AD (BMI: OR = 1.97, 95%CI: 1.40-2.75; smoking: OR = 1.53, 95%CI: 1.27-1.85). In the case-group comparison, smoking was more strongly associated with the risk of synchronous SP and AD than only AD. Alcohol drinking was positively associated with the risk of AD (OR = 1.28, 95%CI: 1.14-1.44), but no statistically significant difference was observed in risks in the case-group comparison. Furthermore, whole-grain intake was associated with a decreased risk of only AD (OR = 0.78, 95%CI: 0.65-0.93). However, white meat intake was positively associated with risks of only SP when compared with AD cases (OR = 1.60, 95%CI: 1.15-2.23). The current study identified common risk factors such as BMI and smoking as well as different risks of certain factors (e.g., alcohol drinking and whole-grain intake) for SP and AD. However, there were still some factors, especially diet-related factors, that have not been fully elucidated in their association with the two lesions. Further research is needed in future to confirm and develop prevention strategies for different lesions.

Systematic Evaluation of Clinical, Nutritional, and Fecal Microbial Factors for Their Association With Colorectal Polyps.

The identification of risk factors for precursor lesions of colorectal cancer (CRC) holds great promise in the context of prevention. With this study, we aimed to identify patient characteristics associated with colorectal polyps (CPs) and polyp features of potential malignant progression. Furthermore, a potential association with gut microbiota in this context was investigated. In this single-center study, a total of 162 patients with CPs and 91 control patients were included. Multiple variables including information on lifestyle, diet, serum parameters, and gut microbiota, analyzed by 16S-rRNA gene amplicon sequencing and functional imputations (Picrust2), were related to different aspects of CPs. We observed that elevated serum alkaline phosphatase (AP) levels were significantly associated with the presence of high-grade dysplastic polyps. This association was further seen for patients with CRC. Thereby, AP correlated with other parameters of liver function. We did not observe significant changes in the gut microbiota between patients with CP and their respective controls. However, a trend toward a lower alpha-diversity was seen in patients with CRC. Interestingly, AP was identified as a possible clinical effect modifier of stool sample beta diversity. We show for the first time an increased AP in premalignant CP. Furthermore, AP showed a significant influence on the microbial composition of the intestine. Relatively elevated liver enzymes, especially AP, may contribute to the detection of precancerous dysplastic or neoplastic changes in colorectal lesions. The association between elevated AP, premalignant CP, and the microbiome merits further study.

LOGISTICS AND RESULTS OF A COLORECTAL CANCER SCREENING PROGRAM IN A MUNICIPALITY IN THE HINTERLAND OF ALAGOAS.

Colorectal cancer (CRC) has high mortality rates worldwide. In Brazil, it is the second most common cancer in both sexes. Delay in detecting premalignant lesions contributes to increased morbidity and mortality. In this scenario, the Piranhas project was created to track CRC in a low-income population in the hinterland of Alagoas. The study aimed to establish the main strategies and verify the feasibility of implementing a CRC tracking program and demonstrate the results obtained in the CRC Prevention Campaign in Piranhas/AL. The program took place in Piranhas, Alagoas, Brazil, through public-private partnerships. Individuals aged between 50 and 70 years of age were included for screening with a fecal occult blood test (FOBT) and colonoscopy in positive cases. Patient data were collected on standard forms. A total of 2152 patients, aged between 50 and 70 years, were screened, 130 of which underwent colonoscopy. Several preneoplastic lesions were detected in 58 patients. The adenoma detection rate (ADR) was 33.85%. The study proved to be effective and viable since 44.6% of the program participants, who underwent screening with FOBT, followed by colonoscopy in positive cases, had some type of preneoplastic lesion. In addition, the program generated a significant social impact on the population of Piranhas due to the opportunity to diagnose and treat CRC precursor lesions.

ROLE OF INCISURA ANGULARIS BIOPSY IN GASTRITIS STAGING AND RISK ASSESSMENT OF GASTRIC CÂNCER.

Gastric atrophy (GA) and intestinal metaplasia (IM) are early stages in the development of gastric cancer. Evaluations are based on the Updated Sydney System, which includes a biopsy of the incisura angularis (IA), and the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis Assessment using Intestinal Metaplasia (OLGIM) gastric cancer risk staging systems. To compare the OLGA and OLGIM classifications with and without IA biopsy. In addition, to determine the prevalence of Helicobacter pylori (HP) and pre-neoplastic changes (GA and IM) in different biopsied regions and to identify the exclusive findings of IA. Observational, prospective, descriptive, unicentric study with 350 patients without a diagnosis of gastric cancer, who underwent upper digestive endoscopy with biopsies at Gastroclínica Itajaí, from March 2020 to May 2022. The histopathological classification of gastritis followed the Updated Sydney System, and the gastric cancer risk assessment followed the OLGA and OLGIM systems. The methodology applied evaluated the scores of the OLGA and OLGIM systems with and without the assessment of the IA biopsy. Statistical analysis was performed using descriptive measures (frequencies, percentages, mean, standard deviation, 95% confidence interval). Ranks were compared using the Kruskal-Wallis or Wilcoxon tests. To analyze the relationship between the frequencies, the bilateral Fisher’s exact test was used. Wilson’s score with continuity correction was applied to the confidence interval. The median age was 54.7 years, with 52.57% female and 47.43% male patients. The comparison between the used biopsies protocol (corpus + antrum [CA] vs corpus + antrum + incisura angularis [CAI]) and the OLGA and OLGIM stages showed a significant decrease in both staging systems when the biopsy protocol restricted to the corpus and antrum was applied (OLGA CAI vs CA; P=0.008 / OLGIM CAI vs CA; P=0.002). The prevalence of pre-malignant lesions (GA, IM and dysplasia) of the gastric mucosa was (33.4%, 34% and 1.1%, respectively) in the total sample. The antrum region exhibited significantly higher numbers of alteration (P<0.001), except for HP infection, which was present in 24.8% of the patients. Incisura angularis biopsy is important because it increased the number of cases diagnosed in more advanced stages of intestinal metaplasia and atrophy. The study had limitations, with the main one being the relatively small sample size, consisting mostly of healthy individuals, although mostly elderly.

Consensus molecular subtype transition during progression of colorectal cancer.

The consensus molecular subtype (CMS) classification divides colorectal cancer (CRC) into four distinct subtypes based on RNA expression profiles. The biological differences between CMSs are already present in CRC precursor lesions, but not all CMSs pose the same risk of malignant transformation. To fully understand the path to malignant transformation and to determine whether CMS is a fixed entity during progression, genomic and transcriptomic data from two regions of the same CRC lesion were compared: the precursor region and the carcinoma region. In total, 24 patients who underwent endoscopic removal of T1-2 CRC were included. Regions were subtyped for CMS and DNA mutation analysis was performed. Additionally, a set of 85 benign adenomas was CMS-subtyped. This analysis revealed that almost all benign adenomas were classified as CMS3 (91.8%). In contrast, CMS2 was the most prevalent subtype in precursor regions (66.7%), followed by CMS3 (29.2%). CMS4 was absent in precursor lesions and originated at the carcinoma stage. Importantly, CMS switching occurred in a substantial number of cases and almost all (six out of seven) CMS3 precursor regions showed a shift to a different subtype in the carcinoma part of the lesion, which in four cases was classified as CMS4. In conclusion, our data indicate that CMS3 is related to a more indolent type of precursor lesion that less likely progresses to CRC and when this occurs, it is often associated with a subtype change that includes the more aggressive mesenchymal CMS4. In contrast, an acquired CMS2 signature appeared to be rather fixed during early CRC development. Combined, our data show that subtype changes occur during progression and that CMS3 switching is related to changes in the genomic background through acquisition of a novel driver mutation (TP53) or selective expansion of a clone, but also occurred independently of such genetic changes. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Clinical and endoscopic characteristics and management of 220 cases with serrated polyps

BackgroundSerrated polyps are considered the precursor lesions of colorectal cancer through the serrated pathway. In the present study, we aimed to evaluate and discuss the clinical and endoscopic characteristics and management of serrated polyps. MethodsThe data of 220 cases with serrated polyps between September 2018 and November 2021 in Shenzhen People's Hospital were retrospectively analyzed. ResultsOf all these cases, 32 were hyperplastic polyps, 36 were traditional serrated adenomas, 126 were sessile serrated lesions, 25 were SSLs with dysplasia, and one was an unclassified serrated adenoma. Although most patients were males aged ≥50 years and most serrated polyps were located in the distal colon and rectum with a size of 6–10 mm and the shape of type 0-Is, there was no significant difference (P > 0.05). Serrated polyps of ≤5 mm in size and type 0-IIa were mostly removed by cold biopsy forceps. Cold snare polypectomy was primarily used for those of 6–10 mm in size. Endoscopic mucosal resection was used for those of 6–20 mm, and endoscopic submucosal dissection was used for those of ≥20 mm (P < 0.05). All complications occurred in SSL patients with or without dysplasia (P < 0.05). ConclusionsClinical and endoscopic characteristics were beneficial for distinguishing and diagnosing serrated polyps. In addition, management options were crucial to prevent recurrence and progression. However, the detection rate of serrated polyps was relatively low. Therefore, prospective multicenter studies with large samples are necessary to better assess colorectal serrated polyps.

Comparison of synchronous neoplasms at colonoscopic diagnosis of early-onset versus average-onset colorectal cancer.

3623 Background: Colorectal cancer (CRC) incidence has steadily increased in adults younger than 50 years (EO-CRC) since the 1990s, with a predominance in the left colon and rectum. Precursor lesions of CRCs are adenomas, including advanced adenomas, and sessile serrated polyps. Given that neoplastic development is age-related, we hypothesized that patients with early-onset CRC (EO-CRC) may have fewer adenomas compared to patients with average-onset CRC (AO-CRC) at diagnosis. Methods: We performed a retrospective review of electronic health records at Mayo Clinic or Mayo Health System [2012 to 2021] and randomly selected 150 patients with EO-CRC who met eligibility criteria and matched them with 150 AO-CRC patients based on gender and colonoscopy indication. Known hereditary syndromes or inflammatory bowel disease were excluded. At colonoscopy where CRC was diagnosed, we recorded findings of adenomas, advanced adenomas (&gt; 1 cm, villous histology, or high-grade dysplasia), and sessile serrated polyps (SSP). Results: Median age at diagnosis was 43 years for EO-CRC and 67 years for AO-CRC. No significant differences in BMI, family history of CRC, MMR, BRAFV 600E KRAS status or SSPs were found between groups (all p &gt; 0.05). Among patients with colon cancer, no difference was found for adenoma number yet patients with EO-colon cancer (EO-CC) had larger polyps [median of 10 mm vs 5 mm, p = 0.001] (Table) compared with AO-colon cancer (AO-CC). At least 1 adenoma was found in 56% and 47% of patients with EO-CC and AO-CC, respectively. Moreover, advanced adenomas were significantly more common in the EO-CC group compared with the AO-CC group (42% and 14%, p &lt; 0.001) [ Table]. Among patients with rectal cancer, non-advanced adenomas were less frequent and although advanced adenoma were similar in frequency, they were more commonly located in the rectum in EO-rectal compared to AO-rectal cancers (Table). Conclusions: Patients with EO-colon cancer had a significantly higher likelihood of a synchronous advanced adenoma in the colon compared to those with AO-CRC. Together, these data suggest accelerated carcinogenesis throughout the colorectum in early onset patients, with increased risk for development of synchronous and metachronous CRC. [Table: see text]

Pterostilbene and Probiotic Complex in Chemoprevention of Putative Precursor Lesions for Colorectal Cancer in an Experimental Model of Intestinal Carcinogenesis with 1,2-Dimethylhydrazine

Dietary supplementation with pterostilbene (PS) and/or a probiotic (PRO) may ameliorate the intestinal microbiota in disease conditions. This study aims to evaluate PS and PRO for the chemoprevention of putative precursor lesions for colorectal cancer (CRC) in an experimental model of intestinal carcinogenesis with 1,2-dimethylhydrazine (1,2-DMH). Sixty male Wistar rats were equally divided into five groups: Sham, 1,2-DMH, 1,2-DMH + PS, 1,2-DMH + PRO, and 1,2-DMH + PS + PRO. PRO (5 × 107/mL) was offered in water, and PS (300 ppm) was provided in the diet ad libitum. 1,2-DMH (20 mg/kg/week) was administered for 15 consecutive weeks. In the 25th week, proctocolectomy was conducted. PRO alone and PRO combined with PS were the best intervention strategies to improve experimental 1,2-DMH-induced CRC regarding several parameters of carcinogenesis. Our findings may contribute to the development of novel preventive strategies for CRC and may help to identify novel modulators of colon carcinogenesis.

Comparison of precursor neoplasms at colonoscopic diagnosis of early-onset and later-onset colon cancer.

74 Background: Colorectal cancer (CRC) incidence has steadily increased in adults younger than 50 years (EO-CRC) since the 1990s, with a reported higher prevalence in the left colon and rectum. Established precursor lesions of CRCs are adenomas, including advanced adenomas, and sessile serrated polyps. We hypothesized that patients at diagnosis of early-onset colon cancer (EO-CC) would have fewer adenomas compared to patients with later-onset colon cancer (LO-CC). Methods: We performed a retrospective review of electronic health records and identified 58 patients diagnosed with EO-CC who had colonoscopy at Mayo Clinic or Mayo Health System who were then matched with 58 LO-CC patients based on gender and procedure indication (diagnostic in 76%, surveillance 16%, screening 8%)[2012 to 2021]. At colonoscopy where colon cancer was diagnosed, we recorded findings of adenomas, advanced adenomas (≥ 1 cm, villous histology, and/or high-grade dysplasia) and sessile serrated polyps. On CCs, limited molecular data were available [mismatch repair (MMR); BRAFV600E, KRAS]. Results: Among 116 patients included in the EO-CC and LO-CC study arms, the median age at cancer diagnosis were 42 and 74 years, respectively. No significant differences were found between study arms and risk factors for CRC including tobacco, alcohol, BMI, genetic syndromes, family history of CRC, and MMR, BRAFV600E or KRAS status (all p&gt; 0.05). While no difference was found for polyp number by arm, patients with EO-CC had larger polyps (median of 10 mm vs 6 mm, p=0.001) compared with LO-CC. At least 1 adenoma was found in 50% and 52% of patients with EO-CC and LO-CC, respectively. Importantly, advanced adenomas were significantly more common in the EO-CC group compared with the LO-CC group (41% and 21%, p=0.027). Sidedness of all adenomas did not differ significantly for EO-CC vs LO-CCs. Conclusions: Patients found to have a primary EO-CC had a significantly higher likelihood of a synchronous advanced adenoma in the colon compared to those with a primary LO-CRC. Together, these data suggest accelerated carcinogenesis throughout the colorectum with increased risk of synchronous and metachronous patients with EO-CC. [Table: see text]

Association between atherogenic index of plasma and colorectal neoplasms in patients with hypertension.

Association between atherogenic index of plasma and colorectal neoplasms in patients with hypertension.

Adenoma Dysplasia Grading of Colorectal Polyps Using Fast Fourier Convolutional ResNet (FFC-ResNet)

Colorectal polyps are precursor lesions of colorectal cancer; hence, early detection and dysplasia grading of polyps are essential for determining cancer risk, the possibility of developing subsequent polyps, and follow-up recommendations. The significant contribution of this study is the development of an enhanced deep-learning model called Fast Fourier Convolutional ResNet (FFC-ResNet) to classify dysplasia grades of polyps. It is based on the ResNet-50 architecture and uses cross-feature fusion, which combines local features extracted using conventional spatial convolution with global features extracted using Fourier convolution. Because of the compensatory effect between local and global features, the learnability and performance of FFC-ResNet have increased. The proposed FFC-ResNet was developed and tested using UniToPatho, a dataset containing 7000 μm and 800 μm hematoxylin-and-eosin (H&E)-stained colorectal images. And a favourable performance of sensitivity 0.95, specificity 0.93, balance accuracy 0.94, precision 0.95, F1 score 0.95 and AUC 0.99 was obtained using 800 μm polyp patches.

Somatic targeted mutation profiling of colorectal cancer precursor lesions

BackgroundMost colorectal cancers (CRC) arise from precursor lesions. This study aimed to characterize the mutation profile of colorectal cancer precursor lesions in a Brazilian population.MethodsIn total, 90 formalin-fixed paraffin-embedded colorectal precursor lesions, including 67 adenomas, 7 sessile serrated lesions, and 16 hyperplastic polyps, were analyzed by next-generation sequencing using a panel of 50 oncogenes and tumor suppressor genes. The genetic ancestry of the patients was estimated.ResultsSomatic driver mutations were identified in 66.7% of cases, including alterations in APC (32.2%), TP53 (20.0%), KRAS (18.9%), BRAF (13.3%) and EGFR (7.8%). Adenomas displayed a higher number of mutations, mainly in APC, compared to serrated polyps (73.1% vs. 47.8%, p = 0.026). Advanced adenomas had a significantly higher frequency of mutation in KRAS and a high overall mutation rate than early adenomas (92.9% vs. 59%, p = 0.006). A high degree of ancestry admixture was observed in the population studied, with a predominance of European components (mean of 73%) followed by African (mean of 11.3%). No association between genetic ancestry and type of lesions was found. The mutation profile of Brazilian colorectal precursor lesions exhibits alteration in APC, KRAS, TP53, and BRAF at different frequencies according to lesion type.ConclusionsThese results bestow the knowledge of CRC's biologic history and support the potential of these biomarkers for precursor lesions detection in CRC screening of the Brazilian population.

Current Approaches in Managing Colonic Serrated Polyps and Serrated Polyposis.

For decades, conventional adenomas were the only known precursor lesions of colorectal cancer (CRC). Accordingly, education and research regarding CRC prevention were mainly focused on adenomas. The groundbreaking discovery that serrated polyps (SPs) also have the potential to develop into CRCs, and seem to account for a considerable proportion of sporadic CRCs, has led to a paradigm shift in the prevention, diagnosis, and treatment of CRC. Studies in recent years have led to our current understanding of SPs and associated CRC, but a lot of work is still to be done to further improve knowledge about this serrated neoplasia pathway and the clinical management of SPs and serrated polyposis syndrome (SPS). In this review, we reflect on the current understanding of SPs with respect to terminology, detection, resection, and surveillance and reflect on the management of SPS.

Expression of the EGFR-RAS Inhibitory Proteins DOK1 and MTMR7 and its Significance in Colorectal Adenoma and Adenoma Recurrence.

Colorectal adenomas are precursor lesions for colorectal cancer (CRC), a major cause of cancer-related death. Despite all molecular insights, there are still unknown variables in the development of CRC as well as uncertainties regarding adenoma recurrence after resection. We aimed to characterize the expression of docking protein 1 (DOK1) and myotubularin-related protein 7 (MTMR7), which share inhibiting functions on EGFR-RAS-signalling, a major oncogenic driver in CRC, and their association with clinical variables and adenoma recurrence. This observational study is based on clinical data obtained from patients who underwent routine endoscopy and consecutive follow-up examinations. Immunohistochemistry was conducted both in dysplastic tissue and adjacent non-dysplastic mucosa followed by microscopical assessment. Recurrence was differentiated between local, segmental and distant relapse. A total of 56 patients (23 females) gathering 96 adenomas/polyps were included. 36 patients experienced a metachronous lesion, 23 patients had simultaneous lesions in their index endoscopy. Female patients showed lower levels of MTMR7 in adenomas (p=0.0318). Adenomas of young patients showed lower DOK1 than those of older patients (p=0.0469). Big adenomas showed a higher expression of DOK1 than small lesions (p=0.0044). In serrated lesions, DOK1 was reduced (p=0.0026) and correlated with the quantity of lesions (p < 0.001). MTMR7 was significantly reduced in distant (p=0.05) and local segmental recurrence (p=0.0362), while DOK1 showed higher expression in recurrence (p=0.0291). We found ambivalent results regarding the role of the markers as potential tumor suppressors, implying a context-dependent function of these molecules which might change in the course of time. DOK1 may play an inhibiting role in the serrated pathway. Remarkably, molecular markers have the potential to predict recurrence, since a combined expression analysis of high DOK1 and low MTMR7 correlated with the likelihood of segmental adenoma recurrence.

Prevalence of Colorectal Polyps Based on Cardiorespiratory Fitness, Muscle Strength, Health Behavior, and Abdominal Obesity in Asymptomatic Elderly.

Colorectal polyps are precursor lesions of colorectal cancer and are known to be associated with obesity, low physical activity, and unhealthy behavior. This cross-sectional study analyzed the prevalence of colorectal polyps based on cardiorespiratory fitness (CRF), muscle strength, and health behavior in older adults. Participants were asymptomatic and included 1024 men and 472 women aged 65–80 years who visited the health care center. Colonoscopy was performed under conscious sedation, and cardiorespiratory fitness was measured as the maximum oxygen uptake using gas analysis. Muscle strength was determined using isokinetic equipment, and physical activity, alcohol consumption, and smoking status were investigated using questionnaires. Waist circumference was measured at the thickest part of the middle of the abdomen. Logistic regression analysis was used to calculate the prevalence of colorectal polyps using odds ratios (ORs) based on the variables. The incidence of colorectal polyps was 65.2% in men and 48.5% in women. The ORs of colorectal polyps for obesity were 1.151 (95% confidence interval [CI], 1.010–2.291) and 1.178 (95% CI, 1.015–2.612) in men and women, respectively. The OR for colorectal polyps in male current smokers was 1.884. The ORs for low CRF were 1.985 and 1.841 in men and women, respectively, compared with high CRF. The prevalence of polyps increased with low muscle strength (men’s OR 1.343 women’s OR 1.440) and physical activity in both men (OR 1.693) and women (OR 1.861). In conclusion, lower CRF and muscle strength were associated with an increased prevalence of colorectal polyps in men and women. In both sexes, high waist circumference and low physical activity increased the prevalence of colorectal polyps.

Automatic image and text-based description for colorectal polyps using BASIC classification

Colorectal polyps (CRP) are precursor lesions of colorectal cancer (CRC). Correct identification of CRPs during in-vivo colonoscopy is supported by the endoscopist's expertise and medical classification models. A recent developed classification model is the Blue light imaging Adenoma Serrated International Classification (BASIC) which describes the differences between non-neoplastic and neoplastic lesions acquired with blue light imaging (BLI). Computer-aided detection (CADe) and diagnosis (CADx) systems are efficient at visually assisting with medical decisions but fall short at translating decisions into relevant clinical information. The communication between machine and medical expert is of crucial importance to improve diagnosis of CRP during in-vivo procedures. In this work, the combination of a polyp image classification model and a language model is proposed to develop a CADx system that automatically generates text comparable to the human language employed by endoscopists. The developed system generates equivalent sentences as the human-reference and describes CRP images acquired with white light (WL), blue light imaging (BLI) and linked color imaging (LCI). An image feature encoder and a BERT module are employed to build the AI model and an external test set is used to evaluate the results and compute the linguistic metrics. The experimental results show the construction of complete sentences with an established metric scores of BLEU-1 = 0.67, ROUGE-L = 0.83 and METEOR = 0.50. The developed CADx system for automatic CRP image captioning facilitates future advances towards automatic reporting and may help reduce time-consuming histology assessment.