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Clinical Interventions in Aging 2016Most colon tumors develop via a multistep process involving a series of histological, morphological, and genetic changes that accumulate over time. This has allowed for... (Review)
Review
Most colon tumors develop via a multistep process involving a series of histological, morphological, and genetic changes that accumulate over time. This has allowed for screening and detection of early-stage precancerous polyps before they become cancerous in individuals at average risk for colorectal cancer (CRC), which may lead to substantial decreases in the incidence of CRC. Despite the known benefits of early screening, CRC remains the second leading cause of cancer-related deaths in the United States. Hence, it is important for health care providers to have an understanding of the risk factors for CRC and various stages of disease development in order to recommend appropriate screening strategies. This article provides an overview of the histological/molecular changes that characterize the development of CRC. It describes the available CRC screening methods and their advantages and limitations and highlights the stages of CRC development in which each screening method is most effective.
Topics: Colonography, Computed Tomographic; Colorectal Neoplasms; Early Detection of Cancer; Genetic Testing; Humans; Mass Screening; Polyps; Precancerous Conditions; Risk Factors; Sigmoidoscopy; United States
PubMed: 27486317
DOI: 10.2147/CIA.S109285 -
Cureus Apr 2023Colorectal cancer (CRC) is a significant cause of morbidity and mortality worldwide. National screening guidelines have been implemented to identify and remove... (Review)
Review
Colorectal cancer (CRC) is a significant cause of morbidity and mortality worldwide. National screening guidelines have been implemented to identify and remove precancerous polyps before they become cancer. Routine CRC screening is advised for people with average risk starting at age 45 because it is a common and preventable malignancy. Various screening modalities are currently in use, ranging from stool-based tests (fecal occult blood test (FOBT), fecal immunochemical test (FIT), and FIT-DNA test), radiologic tests (computed tomographic colonography (CTC), double contrast barium enema), and visual endoscopic examinations (flexible sigmoidoscopy (FS), colonoscopy, and colon capsule endoscopy (CCE)) with their varying sensitivity and specificity. Biomarkers also play a vital role in assessing the recurrence of CRC. This review offers a summary of the current screening options, including biomarkers available to detect CRC, highlighting the benefits and challenges encompassing each screening modality.
PubMed: 37193451
DOI: 10.7759/cureus.37509 -
Nature Genetics Jul 2022To chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated...
To chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated single-cell chromatin accessibility profiles and single-cell transcriptomes from 1,000 to 10,000 cells per sample for 48 polyps, 27 normal tissues and 6 CRCs collected from patients with or without germline APC mutations. A large fraction of polyp and CRC cells exhibit a stem-like phenotype, and we define a continuum of epigenetic and transcriptional changes occurring in these stem-like cells as they progress from homeostasis to CRC. Advanced polyps contain increasing numbers of stem-like cells, regulatory T cells and a subtype of pre-cancer-associated fibroblasts. In the cancerous state, we observe T cell exhaustion, RUNX1-regulated cancer-associated fibroblasts and increasing accessibility associated with HNF4A motifs in epithelia. DNA methylation changes in sporadic CRC are strongly anti-correlated with accessibility changes along this continuum, further identifying regulatory markers for molecular staging of polyps.
Topics: Adenoma; Cell Transformation, Neoplastic; Colorectal Neoplasms; DNA Methylation; Humans; Single-Cell Analysis
PubMed: 35726067
DOI: 10.1038/s41588-022-01088-x -
The New England Journal of Medicine Apr 2014An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening.
BACKGROUND
An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening.
METHODS
We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings.
RESULTS
Of the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P=0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P=0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT.
CONCLUSIONS
In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results. (Funded by Exact Sciences; ClinicalTrials.gov number, NCT01397747.).
Topics: Actins; Aged; Aged, 80 and over; Bone Morphogenetic Protein 3; Chromosome Aberrations; Colorectal Neoplasms; DNA Mutational Analysis; DNA, Neoplasm; Early Detection of Cancer; Feces; Female; Genetic Predisposition to Disease; Humans; Immunologic Techniques; Male; Mass Screening; Middle Aged; Muscle Proteins; Mutation; Nerve Tissue Proteins; Occult Blood; Precancerous Conditions; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins
PubMed: 24645800
DOI: 10.1056/NEJMoa1311194 -
World Journal of Gastroenterology May 2020In recent years, the serrated neoplasia pathway where serrated polyps arise as a colorectal cancer has gained considerable attention as a new carcinogenic pathway.... (Review)
Review
In recent years, the serrated neoplasia pathway where serrated polyps arise as a colorectal cancer has gained considerable attention as a new carcinogenic pathway. Colorectal serrated polyps are histopathologically classified into hyperplastic polyps (HPs), sessile serrated lesions, and traditional serrated adenomas; in the serrated neoplasia pathway, the latter two are considered to be premalignant. In western countries, all colorectal polyps, including serrated polyps, apart from diminutive rectosigmoid HPs are removed. However, in Asian countries, the treatment strategy for colorectal serrated polyps has remained unestablished. Therefore, in this review, we described the clinicopathological features of colorectal serrated polyps and proposed to remove HPs and sessile serrated lesions ≥ 6 mm in size, and traditional serrated adenomas of any size.
Topics: Adenoma; Clinical Decision-Making; Colectomy; Colon; Colonic Polyps; Colorectal Neoplasms; Humans; Hyperplasia; Intestinal Mucosa; Narrow Band Imaging; Practice Guidelines as Topic; Precancerous Conditions; Proctectomy; Rectum; Treatment Outcome
PubMed: 32476792
DOI: 10.3748/wjg.v26.i19.2276 -
Circulation Aug 2018Heart failure (HF) survival has improved, and nowadays, many patients with HF die of noncardiac causes, including cancer. Our aim was to investigate whether a causal...
BACKGROUND
Heart failure (HF) survival has improved, and nowadays, many patients with HF die of noncardiac causes, including cancer. Our aim was to investigate whether a causal relationship exists between HF and the development of cancer.
METHODS
HF was induced by inflicting large anterior myocardial infarction in APC mice, which are prone to developing precancerous intestinal tumors, and tumor growth was measured. In addition, to rule out hemodynamic impairment, a heterotopic heart transplantation model was used in which an infarcted or sham-operated heart was transplanted into a recipient mouse while the native heart was left in situ. After 6 weeks, tumor number, volume, and proliferation were quantified. Candidate secreted proteins were selected because they were previously associated both with (colon) tumor growth and with myocardial production in post-myocardial infarction proteomic studies. Myocardial gene expression levels of these selected candidates were analyzed, as well as their proliferative effects on HT-29 (colon cancer) cells. We validated these candidates by measuring them in plasma of healthy subjects and patients with HF. Finally, we associated the relation between cardiac specific and inflammatory biomarkers and new-onset cancer in a large, prospective general population cohort.
RESULTS
The presence of failing hearts, both native and heterotopically transplanted, resulted in significantly increased intestinal tumor load of 2.4-fold in APC mice (all P<0.0001). The severity of left ventricular dysfunction and fibrotic scar strongly correlated with tumor growth ( P=0.002 and P=0.016, respectively). We identified several proteins (including serpinA3 and A1, fibronectin, ceruloplasmin, and paraoxonase 1) that were elevated in human patients with chronic HF (n=101) compared with healthy subjects (n=180; P<0.001). Functionally, serpinA3 resulted in marked proliferation effects in human colon cancer (HT-29) cells, associated with Akt-S6 phosphorylation. Finally, elevated cardiac and inflammation biomarkers in apparently healthy humans (n=8319) were predictive of new-onset cancer (n=1124) independently of risk factors for cancer (age, smoking status, and body mass index).
CONCLUSIONS
We demonstrate that the presence of HF is associated with enhanced tumor growth and that this is independent of hemodynamic impairment and could be caused by cardiac excreted factors. A diagnosis of HF may therefore be considered a risk factor for incident cancer.
Topics: Adenomatous Polyps; Adult; Aged; Animals; Anterior Wall Myocardial Infarction; Case-Control Studies; Cell Proliferation; Disease Models, Animal; Female; Genes, APC; HT29 Cells; Heart Failure; Humans; Inflammation Mediators; Intercellular Signaling Peptides and Proteins; Intestinal Neoplasms; Intestinal Polyps; Male; Mice, Inbred C57BL; Mice, Transgenic; Middle Aged; Prognosis; Risk Assessment; Risk Factors; Signal Transduction; Time Factors; Tumor Burden; Ventricular Remodeling
PubMed: 29459363
DOI: 10.1161/CIRCULATIONAHA.117.030816 -
Journal of Clinical Pathology Aug 2006A major proportion of the workload in many histopathology laboratories is accounted for by endometrial biopsies, either curettage specimens or outpatient biopsy... (Review)
Review
A major proportion of the workload in many histopathology laboratories is accounted for by endometrial biopsies, either curettage specimens or outpatient biopsy specimens. The increasing use of pipelle and other methods of biopsy not necessitating general anaesthesia has resulted in greater numbers of specimens with scant tissue, resulting in problems in assessing adequacy and in interpreting artefactual changes, some of which appear more common with outpatient biopsies. In this review, the criteria for adequacy and common artefacts in endometrial biopsies, as well as the interpretation of endometrial biopsies in general, are discussed, concentrating on areas that cause problems for pathologists. An adequate clinical history, including knowledge of the age, menstrual history and menopausal status, and information on the use of exogenous hormones and tamoxifen, is necessary for the pathologist to critically evaluate endometrial biopsies. Topics such as endometritis, endometrial polyps, changes that are induced by hormones and tamoxifen within the endometrium, endometrial metaplasias and hyperplasias, atypical polypoid adenomyoma, adenofibroma, adenosarcoma, histological types of endometrial carcinoma and grading of endometrial carcinomas are discussed with regard to endometrial biopsy specimens rather than hysterectomy specimens. The value of ancillary techniques, especially immunohistochemistry, is discussed where appropriate.
Topics: Algorithms; Artifacts; Biopsy; Curettage; Diagnosis, Differential; Endometrial Hyperplasia; Endometrial Neoplasms; Endometritis; Endometrium; Estrogen Replacement Therapy; Female; Humans; Precancerous Conditions
PubMed: 16873562
DOI: 10.1136/jcp.2005.029702 -
World Journal of Gastrointestinal... Feb 2022The most common histological type of gastric cancer (GC) is gastric adenocarcinoma arising from the gastric epithelium. Less common variants include mesenchymal,... (Review)
Review
The most common histological type of gastric cancer (GC) is gastric adenocarcinoma arising from the gastric epithelium. Less common variants include mesenchymal, lymphoproliferative and neuroendocrine neoplasms. The Lauren scheme classifies GC into intestinal type, diffuse type and mixed type. The WHO classification includes papillary, tubular, mucinous, poorly cohesive and mixed GC. Chronic atrophic gastritis (CAG) and intestinal metaplasia are recommended as common precancerous conditions. No definite precancerous condition of diffuse/poorly/undifferentiated type is recommended. Chronic superficial inflammation and hyperplasia of foveolar cells may be the focus. Presently, the management of early GC and precancerous conditions mainly relies on endoscopy including diagnosis, treatment and surveillance. Management of precancerous conditions promotes the early detection and treatment of early GC, and even prevent the occurrence of GC. In the review, precancerous conditions including CAG, metaplasia, foveolar hyperplasia and gastric hyperplastic polyps derived from the gastric epithelium have been concluded, based on the overview of gastric epithelial histological organization and its renewal.
PubMed: 35317321
DOI: 10.4251/wjgo.v14.i2.396 -
World Journal of Gastroenterology Aug 2021Colorectal cancer remains a leading cause of morbidity and mortality in the United States. Advances in artificial intelligence (AI), specifically computer aided... (Review)
Review
Colorectal cancer remains a leading cause of morbidity and mortality in the United States. Advances in artificial intelligence (AI), specifically computer aided detection and computer-aided diagnosis offer promising methods of increasing adenoma detection rates with the goal of removing more pre-cancerous polyps. Conversely, these methods also may allow for smaller non-cancerous lesions to be diagnosed and left in place, decreasing the risks that come with unnecessary polypectomies. This review will provide an overview of current advances in the use of AI in colonoscopy to aid in polyp detection and characterization as well as areas of developing research.
Topics: Adenoma; Artificial Intelligence; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Humans
PubMed: 34447227
DOI: 10.3748/wjg.v27.i29.4802