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Gastroenterology Jul 2023Colonic adenomatous polyps, or adenomas, are frequent precancerous lesions and the origin of most cases of colorectal adenocarcinoma. However, we know from epidemiologic...
BACKGROUND & AIMS
Colonic adenomatous polyps, or adenomas, are frequent precancerous lesions and the origin of most cases of colorectal adenocarcinoma. However, we know from epidemiologic studies that although most colorectal cancers (CRCs) originate from adenomas, only a small fraction of adenomas (3%-5%) ever progress to cancer. At present, there are no molecular markers to guide follow-up surveillance programs.
METHODS
We profiled, by mass spectrometry-based proteomics combined with machine learning analysis, a selected cohort of formalin-fixed, paraffin-embedded high-grade (HG) adenomas with long clinical follow-up, collected as part of the Danish national screening program. We grouped subjects in the cohort according to their subsequent history of findings: a nonmetachronous advanced neoplasia group (G0), with no new HG adenomas or CRCs up to 10 years after polypectomy, and a metachronous advanced neoplasia group (G1) where individuals developed a new HG adenoma or CRC within 5 years of diagnosis.
RESULTS
We generated a proteome dataset from 98 selected HG adenoma samples, including 20 technical replicates, of which 45 samples belonged to the nonmetachronous advanced neoplasia group and 53 to the metachronous advanced neoplasia group. The clear distinction of these 2 groups seen in a uniform manifold approximation and projection plot indicated that the information contained within the abundance of the ∼5000 proteins was sufficient to predict the future occurrence of HG adenomas or development of CRC.
CONCLUSIONS
We performed an in-depth analysis of quantitative proteomic data from 98 resected adenoma samples using various novel algorithms and statistical packages and found that their proteome can predict development of metachronous advanced lesions and progression several years in advance.
Topics: Humans; Proteome; Proteomics; Colorectal Neoplasms; Colonic Polyps; Adenoma; Neoplasms, Second Primary; Colonoscopy; Risk Factors
PubMed: 36966943
DOI: 10.1053/j.gastro.2023.03.208 -
Gastroenterology Nov 2023Since the early 2000s, there has been a rapid decline in colorectal cancer (CRC) mortality, due in large part to screening and removal of precancerous polyps. Despite...
DESCRIPTION
Since the early 2000s, there has been a rapid decline in colorectal cancer (CRC) mortality, due in large part to screening and removal of precancerous polyps. Despite these improvements, CRC remains the second leading cause of cancer deaths in the United States, with approximately 53,000 deaths projected in 2023. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review was to describe how individuals should be risk-stratified for CRC screening and post-polypectomy surveillance and to highlight opportunities for future research to fill gaps in the existing literature.
METHODS
This Expert Review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: All individuals with a first-degree relative (defined as a parent, sibling, or child) who was diagnosed with CRC, particularly before the age of 50 years, should be considered at increased risk for CRC. BEST PRACTICE ADVICE 2: All individuals without a personal history of CRC, inflammatory bowel disease, hereditary CRC syndromes, other CRC predisposing conditions, or a family history of CRC should be considered at average risk for CRC. BEST PRACTICE ADVICE 3: Individuals at average risk for CRC should initiate screening at age 45 years and individuals at increased risk for CRC due to having a first-degree relative with CRC should initiate screening 10 years before the age at diagnosis of the youngest affected relative or age 40 years, whichever is earlier. BEST PRACTICE ADVICE 4: Risk stratification for initiation of CRC screening should be based on an individual's age, a known or suspected predisposing hereditary CRC syndrome, and/or a family history of CRC. BEST PRACTICE ADVICE 5: The decision to continue CRC screening in individuals older than 75 years should be individualized, based on an assessment of risks, benefits, screening history, and comorbidities. BEST PRACTICE ADVICE 6: Screening options for individuals at average risk for CRC should include colonoscopy, fecal immunochemical test, flexible sigmoidoscopy plus fecal immunochemical test, multitarget stool DNA fecal immunochemical test, and computed tomography colonography, based on availability and individual preference. BEST PRACTICE ADVICE 7: Colonoscopy should be the screening strategy used for individuals at increased CRC risk. BEST PRACTICE ADVICE 8: The decision to continue post-polypectomy surveillance for individuals older than 75 years should be individualized, based on an assessment of risks, benefits, and comorbidities. BEST PRACTICE ADVICE 9: Risk-stratification tools for CRC screening and post-polypectomy surveillance that emerge from research should be examined for real-world effectiveness and cost-effectiveness in diverse populations (eg, by race, ethnicity, sex, and other sociodemographic factors associated with disparities in CRC outcomes) before widespread implementation.
PubMed: 37737817
DOI: 10.1053/j.gastro.2023.06.033 -
Frontiers in Oncology 2023In colorectal cancer (CRC) energy metabolism research, the precancerous stage of polyp has remained rather unexplored. By now, it has been shown that CRC has not fully...
In colorectal cancer (CRC) energy metabolism research, the precancerous stage of polyp has remained rather unexplored. By now, it has been shown that CRC has not fully obtained the glycolytic phenotype proposed by O. Warburg and rather depends on mitochondrial respiration. However, the pattern of metabolic adaptations during tumorigenesis is still unknown. Understanding the interplay between genetic and metabolic changes that initiate tumor development could provide biomarkers for diagnosing cancer early and targets for new cancer therapeutics. We used human CRC and polyp tissue material and performed high-resolution respirometry and qRT-PCR to detect changes on molecular and functional level with the goal of generally describing metabolic reprogramming during CRC development. Colon polyps were found to have a more glycolytic bioenergetic phenotype than tumors and normal tissues. This was supported by a greater , , , and expression. Despite the increased glycolytic activity, cells in polyps were still able to maintain a highly functional OXPHOS system. The mechanisms of OXPHOS regulation and the preferred substrates are currently unclear and would require further investigation. During polyp formation, intracellular energy transfer pathways become rearranged mainly by increasing the expression of mitochondrial adenylate kinase () and creatine kinase () isoforms. Decreased glycolysis and maintenance of OXPHOS activity, together with the downregulation of the CK system and the most common AK isoforms ( and ), seem to play a relevant role in CRC development.
PubMed: 37342183
DOI: 10.3389/fonc.2023.1171887 -
Biomedicine & Pharmacotherapy =... Nov 2023Colorectal cancer is a prevalent malignant tumor with a complex and diverse pathogenesis. In recent years, natural products have shown promising application prospects as... (Review)
Review
Colorectal cancer is a prevalent malignant tumor with a complex and diverse pathogenesis. In recent years, natural products have shown promising application prospects as sources of anticancer drugs. BBR, a class of benzoquinoline alkaloids extracted from various plants, is widely used in disease treatments owing to its pharmacological activities, including antibacterial, anti-inflammatory, antioxidant, anticancer, and anti-angiogenesis properties. Research has demonstrated that BBR exerts an anti-Salmonella and -Escherichia coli infection effect, attenuating inflammatory reactions by inhibiting harmful bacteria. During the stage of colorectal precancerous lesions, BBR inhibits the activity of cell cyclin by regulating the PI3K/AKT, MAPK, and Wnt signaling pathways, thereby decelerating the cell cycle progression of polyp or adenoma cells. Moreover, the inhibitory effect of BBR on colorectal cancer primarily occurs through the regulation of the cancer cell cycle, anti-angiogenesis, gut microbiota, and antioxidant pathways. The specific involved pathways include the MPK/ERK, NF-kB, and EGFR signaling pathways, encompassing the regulation of Bcl-2 family proteins, vascular endothelial growth factor, and superoxide dismutase. This study reviews and summarizes, for the first time, the specific mechanisms of action of BBR in the carcinogenesis process of colorectal cancer, providing novel insights for its clinical application in intestinal diseases.
PubMed: 37757496
DOI: 10.1016/j.biopha.2023.115571 -
PeerJ 2023Colorectal cancer (CRC), which develops from the gradual evolution of tubular adenomas and serrated polyps in the colon and rectum, has a poor prognosis and a high... (Review)
Review
Colorectal cancer (CRC), which develops from the gradual evolution of tubular adenomas and serrated polyps in the colon and rectum, has a poor prognosis and a high mortality rate. In addition to genetics, lifestyle, and chronic diseases, intestinal integrity and microbiota (which facilitate digestion, metabolism, and immune regulation) could promote CRC development. For example, enterotoxigenic , genotoxic , and , members of the intestinal microbiota, are highly correlated in CRC. This review describes the roles and mechanisms of these three bacteria in CRC development. Their interaction during CRC initiation and progression has also been proposed. Our view is that in the precancerous stage of colorectal cancer, ETBF causes inflammation, leading to potential changes in intestinal ecology that may provide the basic conditions for pks+ colonization and induction of oncogenic mutations, when cancerous intestinal epithelial cells can further recruit to colonise the lesion site and may contribute to CRC advancement by primarily the development of cancer cells, stemization, and proliferation, which could create new and tailored preventive, screening and therapeutic interventions. However, there is the most dominant microbiota in each stage of CRC development, not neglecting the possibility that two or even all three bacteria could be engaged at any stage of the disease. The relationship between the associated gut microbiota and CRC development may provide important information for therapeutic strategies to assess the potential use of the associated gut microbiota in CRC studies, antibiotic therapy, and prevention strategies.
Topics: Humans; Colorectal Neoplasms; Escherichia coli; Bacteria; Rectum
PubMed: 37554340
DOI: 10.7717/peerj.15777 -
Nutrients Sep 2023Colorectal cancer prevention is crucial for public health, given its high mortality rates, particularly in young adults. The early detection and treatment of... (Randomized Controlled Trial)
Randomized Controlled Trial
Colorectal cancer prevention is crucial for public health, given its high mortality rates, particularly in young adults. The early detection and treatment of precancerous lesions is key to preventing carcinogenesis progression. Natural compounds like curcumin and anthocyanins show promise in impeding adenomatous polyp progression in preclinical models. We conducted a randomized, double-blind, placebo-controlled, phase II presurgical trial in 35 patients with adenomatous polyps to explore the biological effects of curcumin and anthocyanins on circulating biomarkers of inflammation and metabolism. No significant difference in biomarker changes by treatment arm was observed. However, the network analysis before treatment revealed inverse correlations between adiponectin and BMI and glycemia, as well as direct links between inflammatory biomarkers and leptin and BMI. In addition, a considerable inverse relationship between adiponectin and grade of dysplasia was detected after treatment (corr = -0.45). Finally, a significant increase in IL-6 at the end of treatment in subjects with high-grade dysplasia was also observed ( = 0.02). The combined treatment of anthocyanins and curcumin did not result in the direct modulation of circulating biomarkers of inflammation and metabolism, but revealed a complex modulation of inflammatory and metabolic biomarkers of colon carcinogenesis.
Topics: Young Adult; Humans; Anthocyanins; Curcumin; Adiponectin; Adenoma; Colorectal Neoplasms; Biomarkers; Carcinogenesis; Hyperplasia; Inflammation
PubMed: 37764678
DOI: 10.3390/nu15183894 -
Clinical Endoscopy Sep 2023Colonoscopy plays an important role in reducing the incidence and mortality of colorectal cancer by detecting adenomas and other precancerous lesions. Image-enhanced... (Review)
Review
Colonoscopy plays an important role in reducing the incidence and mortality of colorectal cancer by detecting adenomas and other precancerous lesions. Image-enhanced endoscopy (IEE) increases lesion visibility by enhancing the microstructure, blood vessels, and mucosal surface color, resulting in the detection of colorectal lesions. In recent years, various IEE techniques have been used in clinical practice, each with its unique characteristics. Numerous studies have reported the effectiveness of IEE in the detection of colorectal lesions. IEEs can be divided into two broad categories according to the nature of the image: images constructed using narrowband wavelength light, such as narrowband imaging and blue laser imaging/blue light imaging, or color images based on white light, such as linked color imaging, texture and color enhancement imaging, and i-scan. Conversely, artificial intelligence (AI) systems, such as computer-aided diagnosis systems, have recently been developed to assist endoscopists in detecting colorectal lesions during colonoscopy. To better understand the features of each IEE, this review presents the effectiveness of each type of IEE and their combination with AI for colorectal lesion detection by referencing the latest research data.
PubMed: 37491990
DOI: 10.5946/ce.2023.055 -
Clinical and Translational... Oct 2023Colorectal cancer screening plays a vital role in early detection and removal of precancerous adenomas, contributing to decreased mortality rates. Most polyps found... (Review)
Review
Colorectal cancer screening plays a vital role in early detection and removal of precancerous adenomas, contributing to decreased mortality rates. Most polyps found during colonoscopies are small and unlikely to harbor advanced neoplasia or invasive cancer, leading to the development of "leave-in-situ" and "resect-and-discard" approaches. These strategies could lead to significant cost savings and efficiencies, but their implementation has been hampered by concerns around financial incentives, medical-legal risks, and local rules for tissue handling. This article reviews the potential of artificial intelligence to enhance the accuracy of polyp diagnosis through computer-aided diagnosis (CADx). While the adoption of CADx in optical biopsy has shown mixed results, it has the potential to significantly improve the management of colorectal polyps. Several studies reviewed in this article highlight the varied results of CADx in optical biopsy for colorectal polyps. Although artificial intelligence does not consistently outperform expert endoscopists, it has the potential to serve as a beneficial secondary reader, aiding in accurate optical diagnosis and increasing the confidence of the endoscopist. These studies indicate that although CADx holds great potential, it is yet to fully meet the performance thresholds necessary for clinical implementation.
Topics: Humans; Colonic Polyps; Artificial Intelligence; Colonoscopy; Adenoma; Narrow Band Imaging
PubMed: 37747097
DOI: 10.14309/ctg.0000000000000640 -
Endoscopy International Open Aug 2023Conventional endoscopic mucosal resection (C-EMR) is limited by low en-bloc resection rates, especially for large (> 20 mm) lesions. Underwater EMR (U-EMR) has emerged... (Review)
Review
Conventional endoscopic mucosal resection (C-EMR) is limited by low en-bloc resection rates, especially for large (> 20 mm) lesions. Underwater EMR (U-EMR) has emerged as an alternative for colorectal polyps and is being shown to improve en-bloc resection rates. We conducted a systematic review and meta-analysis comparing the two techniques. Multiple databases were searched through November 2022 for randomized controlled trials (RCTs) comparing outcomes of U-EMR and C-EMR for colorectal polyps. Meta-analysis was performed to determine pooled proportions and relative risks (RRs) of R0 and en-bloc resection, polyp recurrence, resection time, and adverse events. Seven RCTs with 1458 patients (U-EMR: 739, C-EMR: 719) were included. The pooled rate of en-bloc resection was significantly higher with U-EMR vs C-EMR, 70.17% (confidence interval [CI] 46.68-86.34) vs 58.14% (CI 31.59-80.68), respectively, RR 1.21 (CI 1.01-1.44). R0 resection rates were higher with U-EMR vs C-EMR, 58.1% (CI 29.75-81.9) vs 44.6% (CI 17.4-75.4), RR 1.25 (CI 0.99-1.6). For large polyps (> 20 mm), en-bloc resection rates were comparable between the two techniques, RR 1.24 (CI 0.83-1.84). Resection times were comparable between U-EMR and C-EMR, standardized mean difference -1.21 min (CI -2.57 to -0.16). Overall pooled rates of perforation, and immediate and delayed bleeding were comparable between U-EMR and C-EMR. Pooled rate of polyp recurrence at surveillance colonoscopy was significantly lower with U-EMR than with C-EMR, RR 0.62 (CI 0.41-0.94). Colorectal U-EMR results in higher en-bloc resection and lower recurrence rates when compared to C-EMR. Both techniques have comparable resection times and safety profiles.
PubMed: 37593155
DOI: 10.1055/a-2117-8327