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Gastroenterology Mar 2020Endoscopic screening reduces incidence and mortality of colorectal cancer (CRC) because precursor lesions, such as conventional adenomas or serrated polyps, are removed....
BACKGROUND & AIMS
Endoscopic screening reduces incidence and mortality of colorectal cancer (CRC) because precursor lesions, such as conventional adenomas or serrated polyps, are removed. Individuals with polypectomies are advised to undergo colonoscopy surveillance to prevent CRC. However, guidelines for surveillance intervals after diagnosis of a precursor lesion, particularly for individuals with serrated polyps, vary widely, and lack sufficient supporting evidence. Consequently, some high-risk patients do not receive enough surveillance and lower-risk subjects receive excessive surveillance.
METHODS
We examined the association between findings from first endoscopy and CRC risk among 122,899 participants who underwent flexible sigmoidoscopy or colonoscopy in the Nurses' Health Study 1 (1990-2012), Nurses' Health Study 2 (1989-2013), or the Health Professionals Follow-up Study (1990-2012). Endoscopic findings were categorized as no polyp, conventional adenoma, or serrated polyp (hyperplastic polyp, traditional serrated adenoma, or sessile serrated adenoma, with or without cytological dysplasia). Conventional adenomas were classified as advanced (≥10 mm, high-grade dysplasia, or tubulovillous or villous histology) or nonadvanced, and serrated polyps were assigned to categories of large (≥10 mm) or small (<10 mm). We used a Cox proportional hazards regression model to calculate the hazard ratios (HRs) of CRC incidence, after adjusting for various potential risk factors.
RESULTS
After a median follow-up period of 10 years, we documented 491 incident cases of CRC: 51 occurred in 6161 participants with conventional adenomas, 24 in 5918 participants with serrated polyps, and 427 in 112,107 participants with no polyp. Compared with participants with no polyp detected during initial endoscopy, the multivariable HR for incident CRC in individuals with an advanced adenoma was 4.07 (95% confidence interval [CI] 2.89-5.72) and the HR for CRC in individuals with a large serrated polyp was 3.35 (95% CI 1.37-8.15). In contrast, there was no significant increase in risk of CRC in patients with nonadvanced adenomas (HR 1.21; 95% CI 0.68-2.16, P = .52) or small serrated polyps (HR 1.25; 95% CI 0.76-2.08; P = .38).
CONCLUSIONS
These findings provide support for guidelines that recommend repeat lower endoscopy within 3 years of a diagnosis of advanced adenoma and large serrated polyps. In contrast, patients with nonadvanced adenoma or small serrated polyps may not require more intensive surveillance than patients without polyps.
Topics: Adenoma; Aged; Aged, 80 and over; Colonic Polyps; Colorectal Neoplasms; Female; Follow-Up Studies; Humans; Incidence; Male; Mass Screening; Middle Aged; Neoplasm Seeding; Practice Guidelines as Topic; Precancerous Conditions; Prospective Studies; Retrospective Studies; Risk Assessment; Risk Factors; Sigmoidoscopy; Time Factors
PubMed: 31302144
DOI: 10.1053/j.gastro.2019.06.039 -
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 -
Oncotarget Feb 2017The hypothesis of the local recurrence of preneoplastic lesions was first put forward in the 1950s. Disease recurrence may result from an inherent imbalance in cell... (Review)
Review
The hypothesis of the local recurrence of preneoplastic lesions was first put forward in the 1950s. Disease recurrence may result from an inherent imbalance in cell proliferation that promotes carcinogenesis in apparently normal mucosa. Our review sheds light on how early preneoplastic lesions could be used to diagnose relapsed preneoplastic and, developing neoplastic lesions. We focus in detail on the clinical-pathological and molecular features of adenoma subtypes and their role in relapsed adenoma and their development into colorectal carcinoma. Moreover, we include the data available on microbiota and its metabolites and their role in recurrence. We strongly believe that a significant improvement could be achieved in colorectal screening by introducing personalized endoscopic surveillance for polyp-bearing patients on the basis of the presence of molecular markers that are predictive of recurrence.
Topics: Adenoma; Colon; Colorectal Neoplasms; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Recurrence, Local; Precancerous Conditions; Rectum; Tumor Suppressor Proteins
PubMed: 27902488
DOI: 10.18632/oncotarget.13628 -
Medical Image Computing and... Sep 2022Colonoscopy is a gold standard procedure but is highly operator-dependent. Automated polyp segmentation, a precancerous precursor, can minimize missed rates and timely...
Colonoscopy is a gold standard procedure but is highly operator-dependent. Automated polyp segmentation, a precancerous precursor, can minimize missed rates and timely treatment of colon cancer at an early stage. Even though there are deep learning methods developed for this task, variability in polyp size can impact model training, thereby limiting it to the size attribute of the majority of samples in the training dataset that may provide sub-optimal results to differently sized polyps. In this work, we exploit and features in the form of text attention during training. We introduce an auxiliary classification task to weight the text-based embedding that allows network to learn additional feature representations that can distinctly adapt to differently sized polyps and can adapt to cases with multiple polyps. Our experimental results demonstrate that these added text embeddings improve the overall performance of the model compared to state-of-the-art segmentation methods. We explore four different datasets and provide insights for size-specific improvements. Our proposed (TGANet) can generalize well to variable-sized polyps in different datasets. Codes are available at https://github.com/nikhilroxtomar/TGANet.
PubMed: 36780239
DOI: 10.1007/978-3-031-16437-8_15 -
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 -
Anticancer Research 2006Colon cancer evolves through epithelial cell deregulation and inappropriate proliferation. These histopathological characteristics are exemplified in the biochemical,... (Review)
Review
Colon cancer evolves through epithelial cell deregulation and inappropriate proliferation. These histopathological characteristics are exemplified in the biochemical, immunohistochemical, genetic and epigenetic elements detected within colonic mucosa. Early detection is paramount for the prevention of colon cancer deaths. Aberrant crypt foci (ACF) are thought to be the earliest identifiable neoplastic lesions in the colon carcinogenetic model. The progression of ACF to polyp and, subsequently, to cancer parallels the accumulation of several biochemical alterations and mutations whereby a small fraction of ACF evolve to colon cancer. Recent data indicate that, not uncommonly, some ACF bypass the polyp stage in their carcinogenesis thus reinforcing the importance of their early detection and our understanding of their pathogenesis. Since ACF were first detected in carcinogen-treated mice, research efforts have focused on these microscopically visible lesions both in animal and human models. ACF show variable histological features, characterized by Kudo (20) and, therefore, can be grouped into differing categories by in vivo examination with high-magnification-chromoscopic-colonoscopy (HMCC). As expected, ACF are more frequently detected in distal animal and human colons coinciding with the geographic distribution of colorectal cancer (CRC). Various proteomic (Prot) markers may be altered within ACF suggesting possible prospective pathological changes. These markers include Calreticulin, Transgelin, Serotransferrin, Triphosphate isomerase and Carbonic anhydrase II. Other markers of importance include carcinoembryonic antigen (CEA), B-catenin, placental cadherin (P-cadherin), epithelial cadherin (E-cadherin), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2) and P16INK4a. Genetic mutations of K-ras, B-Raf APC and p53 have been demonstrated in ACF as well as the epigenetic alterations of CpG island methylation. Genomic instabilities (GI), illustrated by a higher GI Index (GII), microsatellite instability (MSI), loss of heterozygosity (LOH) and defects in mismatch repair (MMR) systems, are also expressed. These transformations may lead to the identification of the earliest pathological features initiating colon tumorigenesis. In this review, the advances in ACF research as precursors of CRCs are highlighted.
Topics: Animals; Colorectal Neoplasms; Humans; Intestinal Mucosa; Precancerous Conditions
PubMed: 16475686
DOI: No ID Found -
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 -
Gastrointestinal Endoscopy Clinics of... Oct 2019Colonoscopic polypectomy is fundamental to effective prevention of colorectal cancer. Polypectomy reduces colorectal cancer incidence and mortality by altering the... (Review)
Review
Colonoscopic polypectomy is fundamental to effective prevention of colorectal cancer. Polypectomy reduces colorectal cancer incidence and mortality by altering the natural history and progression of precancerous precursor polyps. Epidemiologic data from the United States, where colorectal cancer rates have been steadily declining in parallel with screening efforts, provide indisputable evidence about the effectiveness of polypectomy. Randomized controlled trials of fecal occult blood tests and flexible sigmoidoscopy, and observational colonoscopy studies, provide additional support. Longitudinal studies have shown variable levels of protection after polypectomy, highlighting the central importance of high quality and adequate surveillance of higher-risk patients.
Topics: Aged; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Evidence-Based Medicine; Female; Humans; Longitudinal Studies; Male; Middle Aged; Precancerous Conditions; Primary Prevention; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; SEER Program; Sigmoidoscopy; Treatment Outcome; United States
PubMed: 31445683
DOI: 10.1016/j.giec.2019.05.001 -
Surgical Endoscopy Feb 2021Removal of pre-cancerous polyps on screening colonoscopy is a mainstay of colorectal cancer (CRC) prevention. Complex polyps may require surgical removal with colectomy,...
BACKGROUND
Removal of pre-cancerous polyps on screening colonoscopy is a mainstay of colorectal cancer (CRC) prevention. Complex polyps may require surgical removal with colectomy, an operation with a 17% morbidity and 1.5% mortality rate. Recently, advanced endoscopic techniques have allowed some patients with complex polyps to avoid the morbidity of colectomy. However, the rate of colectomy for benign polyp in the United States is unclear, and variation in this rate across geographic regions has not been studied. We compared regional variation in colectomy rates for CRC versus benign polyp.
METHODS
We performed a retrospective population-based study of Medicare beneficiaries undergoing colectomy for CRC or benign polyp, using the 100% Medicare Provider Analysis and Review files from 2010 to 2015. We used multivariable linear regression to obtain population-based colectomy rates for CRC and benign polyp at the hospital referral region (HRR) level, adjusted for age, sex, and race.
RESULTS
Of 280,815 patients, 157,802 (65.8%) underwent colectomy for CRC compared to 81,937 (34.2%) for benign polyp. Across HRRs, colectomy rates varied 5.8-fold for cancer (0.32-1.84 per 1000 beneficiaries). However, there was a 69-fold variation for benign polyp (0.01-0.69). While the rate of colectomy for CRC was correlated with the rate of colectomy for benign polyp (slope = 0.61, 95% CI 0.48-0.75), HRRs with the lowest or highest rates of colectomy for CRC did not necessarily have similarly low or high rates for benign polyp.
CONCLUSIONS
The use of colectomy for benign polyp is much more variable compared to CRC, suggesting overuse of colectomy for benign polyp in some regions. This variation may stem from provider-level differences, such as endoscopists' referral practice or skill or surgeons' decision to perform colectomy, or from limited access to advanced endoscopists. Interventions to increase endoscopic resection of benign polyps may spare some patients the morbidity and cost of surgery.
Topics: Aged; Colectomy; Colonic Polyps; Colorectal Neoplasms; Female; Humans; Male; Retrospective Studies
PubMed: 32076864
DOI: 10.1007/s00464-020-07451-5 -
World Journal of Gastroenterology Aug 2018Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in colorectal carcinomas with mutations,... (Review)
Review
Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in colorectal carcinomas with mutations, methylation for DNA repair genes, a CpG island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potentials. Detecting serrated lesions, including SSA/Ps with and without dysplasia/carcinoma, is critical, but SSA/Ps can be difficult to detect, are inconsistently identified by endoscopists and pathologists, and are often incompletely resected. Therefore, SSA/Ps are considered to be major contributors to "interval cancers". If colonoscopists can identify the specific endoscopic characteristics of SSA/Ps, their detection and the effectiveness of colonoscopy may improve. Here, the endoscopic features of SSA/Ps with and without dysplasia/carcinoma, including the characteristics determined using magnifying endoscopy, are reviewed in the context of previous reports. Endoscopically, these subtle polyps are like hyperplastic polyps, because they are slightly elevated and pale. Unlike hyperplastic polyps, SSA/Ps are usually larger than 5 mm, frequently covered by a thin layer called the ''mucus cap'', and are more commonly located in the proximal colon. Magnifying narrow-band imaging findings, which include dark spots inside the crypts and varicose microvascular vessels, in addition to the type II-open pit patterns detected using magnifying chromoendoscopy, effectively differentiate SSA/Ps from hyperplastic polyps. The lesions' endoscopic characteristics, which include their (semi)pedunculated morphologies, double elevations, central depressions, and reddishness, and the use of magnifying endoscopy, might help to detect dysplasia/carcinoma within SSA/Ps. Greater awareness may promote further research into improving the detection, identification, and complete resection rates of SSA/Ps with and without dysplasia/carcinoma and reduce the interval cancer rates.
Topics: Adenoma; Colon; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Humans; Hyperplasia; Mutation; Narrow Band Imaging; Precancerous Conditions; Proto-Oncogene Proteins B-raf
PubMed: 30090005
DOI: 10.3748/wjg.v24.i29.3250