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Palaniappan A, Muthamilselvan S, Sarathi A. COADREADx: A comprehensive algorithmic dissection of colorectal cancer unravels salient biomarkers and actionable insights into its discrete progression. PeerJ 2024; 12:e18347. [PMID: 39484215 PMCID: PMC11526798 DOI: 10.7717/peerj.18347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 09/27/2024] [Indexed: 11/03/2024] Open
Abstract
Background Colorectal cancer is a common condition with an uncommon burden of disease, heterogeneity in manifestation, and no definitive treatment in the advanced stages. Renewed efforts to unravel the genetic drivers of colorectal cancer progression are paramount. Early-stage detection contributes to the success of cancer therapy and increases the likelihood of a favorable prognosis. Here, we have executed a comprehensive computational workflow aimed at uncovering the discrete stagewise genomic drivers of colorectal cancer progression. Methods Using the TCGA COADREAD expression data and clinical metadata, we constructed stage-specific linear models as well as contrast models to identify stage-salient differentially expressed genes. Stage-salient differentially expressed genes with a significant monotone trend of expression across the stages were identified as progression-significant biomarkers. The stage-salient genes were benchmarked using normals-augmented dataset, and cross-referenced with existing knowledge. The candidate biomarkers were used to construct the feature space for learning an optimal model for the digital screening of early-stage colorectal cancers. The candidate biomarkers were also examined for constructing a prognostic model based on survival analysis. Results Among the biomarkers identified are: CRLF1, CALB2, STAC2, UCHL1, KCNG1 (stage-I salient), KLHL34, LPHN3, GREM2, ADCY5, PLAC2, DMRT3 (stage-II salient), PIGR, HABP2, SLC26A9 (stage-III salient), GABRD, DKK1, DLX3, CST6, HOTAIR (stage-IV salient), and CDH3, KRT80, AADACL2, OTOP2, FAM135B, HSP90AB1 (top linear model genes). In particular the study yielded 31 genes that are progression-significant such as ESM1, DKK1, SPDYC, IGFBP1, BIRC7, NKD1, CXCL13, VGLL1, PLAC1, SPERT, UPK2, and interestingly three members of the LY6G6 family. Significant monotonic linear model genes included HIGD1A, ACADS, PEX26, and SPIB. A feature space of just seven biomarkers, namely ESM1, DHRS7C, OTOP3, AADACL2, LPHN3, GABRD, and LPAR1, was sufficient to optimize a RandomForest model that achieved > 98% balanced accuracy (and performant recall) of cancer vs. normal on external validation. Design of an optimal multivariate model based on survival analysis yielded a prognostic panel of three stage-IV salient genes, namely HOTAIR, GABRD, and DKK1. Based on the above sparse signatures, we have developed COADREADx, a web-server for potentially assisting colorectal cancer screening and patient risk stratification. COADREADx provides uncertainty measures for its predictions and needs clinical validation. It has been deployed for experimental non-commercial use at: https://apalanialab.shinyapps.io/coadreadx/.
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Affiliation(s)
- Ashok Palaniappan
- Systems Computational Biology Lab, Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, India
| | - Sangeetha Muthamilselvan
- Systems Computational Biology Lab, Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, India
| | - Arjun Sarathi
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Zhu L, Yuhan J, Yu H, Zhang B, Zhu L, He X, Huang K, Xu W. Aptamer functionalized nucleic acid nano drug for targeted synergistic therapy for colon cancer. J Nanobiotechnology 2023; 21:182. [PMID: 37280622 DOI: 10.1186/s12951-023-01941-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 05/29/2023] [Indexed: 06/08/2023] Open
Abstract
Due to its complicated pathophysiology, propensity for metastasis, and poor prognosis, colon cancer is challenging to treat and must be managed with a combination of therapy. Using rolling circle transcription (RCT), this work created a nanosponge therapeutic medication system (AS1411@antimiR-21@Dox). Using the AS1411 aptamer, this approach accomplished targeted delivery to cancer cells. Furthermore, analysis of cell viability, cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) content, and mitochondrial membrane potential (MMP) levels revealed that functional nucleic acid nanosponge drug (FND) can kill cancer cells. Moreover, transcriptomics uncovered a putative mechanism for the FND anti-tumor effect. These pathways, which included mitotic metaphase and anaphase as well as the SMAC-mediated dissociation of the IAP: caspase complexes, were principally linked to the cell cycle and cell death. In conclusion, by triggering cell cycle arrest and apoptosis, the nano-synergistic therapeutic system allowed for the intelligent and effective targeted administration of RNA and chemotherapeutic medicines for colon cancer treatment. The system allowed for payload efficiency while being customizable, targeted, reliable, stable, and affordable.
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Affiliation(s)
- Liye Zhu
- Food Laboratory of Zhongyuan, Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, No. 17 Qinghua Donglu, Beijing, 100083, China
- College of Veterinary Medicine, China Agricultural University, Beijing, 100094, China
| | - Jieyu Yuhan
- Food Laboratory of Zhongyuan, Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, No. 17 Qinghua Donglu, Beijing, 100083, China
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
| | - Hao Yu
- Food Laboratory of Zhongyuan, Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, No. 17 Qinghua Donglu, Beijing, 100083, China
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
| | - Boyang Zhang
- Food Laboratory of Zhongyuan, Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, No. 17 Qinghua Donglu, Beijing, 100083, China
| | - Longjiao Zhu
- Food Laboratory of Zhongyuan, Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, No. 17 Qinghua Donglu, Beijing, 100083, China
| | - Xiaoyun He
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
| | - Kunlun Huang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
| | - Wentao Xu
- Food Laboratory of Zhongyuan, Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, No. 17 Qinghua Donglu, Beijing, 100083, China.
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.
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Niedermaier T, Gredner T, Hoffmeister M, Mons U, Brenner H. Impact of Reducing Intake of Red and Processed Meat on Colorectal Cancer Incidence in Germany 2020 to 2050-A Simulation Study. Nutrients 2023; 15:nu15041020. [PMID: 36839378 PMCID: PMC9966277 DOI: 10.3390/nu15041020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/10/2023] [Accepted: 02/12/2023] [Indexed: 02/22/2023] Open
Abstract
BACKGROUND According to the International Agency for Research on Cancer (IARC), there is sufficient evidence for the carcinogenicity of processed meat consumption in humans, specifically regarding colorectal cancer (CRC) risk. Evidence for the carcinogenicity of red meat consumption is more limited but points in the same direction. METHODS A macro-simulation approach was used to calculate age- and sex-specific potential impact fractions in a 30-year period (2020-2050). AIMS We estimated numbers and proportions of future CRC cases preventable under different scenarios of reducing the intake of processed and red meat in the German population. RESULTS Eliminating processed meat intake could reduce the burden of CRC by approximately 205,000 cases in Germany (9.6%) in 2020-2050, 2/3 among males (145,000) and 1/3 among females (60,000). Without red meat intake, approximately 63,000 CRC cases could be avoided (2.9%), 39,000 among males and 24,000 among females. Reductions in the mean consumption of both processed and red meat by one or two servings (each 11 or 22 g) per day would be expected to reduce CRC case numbers by 68,000 (3.1%) and 140,000 (6.5%), respectively. CONCLUSION A reduction in red and processed meat intake might substantially reduce the incidence of CRC in Germany. The means of achieving such a reduction might include price and taxation policies, food labeling, and clearer risk communication aiming to reduce individual intake.
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Affiliation(s)
- Tobias Niedermaier
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Correspondence:
| | - Thomas Gredner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Ute Mons
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Cancer Prevention Unit, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
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Katsaounou K, Nicolaou E, Vogazianos P, Brown C, Stavrou M, Teloni S, Hatzis P, Agapiou A, Fragkou E, Tsiaoussis G, Potamitis G, Zaravinos A, Andreou C, Antoniades A, Shiammas C, Apidianakis Y. Colon Cancer: From Epidemiology to Prevention. Metabolites 2022; 12:metabo12060499. [PMID: 35736432 PMCID: PMC9229931 DOI: 10.3390/metabo12060499] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 05/23/2022] [Accepted: 05/24/2022] [Indexed: 02/01/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most prevalent cancers affecting humans, with a complex genetic and environmental aetiology. Unlike cancers with known environmental, heritable, or sex-linked causes, sporadic CRC is hard to foresee and has no molecular biomarkers of risk in clinical use. One in twenty CRC cases presents with an established heritable component. The remaining cases are sporadic and associated with partially obscure genetic, epigenetic, regenerative, microbiological, dietary, and lifestyle factors. To tackle this complexity, we should improve the practice of colonoscopy, which is recommended uniformly beyond a certain age, to include an assessment of biomarkers indicative of individual CRC risk. Ideally, such biomarkers will be causal to the disease and potentially modifiable upon dietary or therapeutic interventions. Multi-omics analysis, including transcriptional, epigenetic as well as metagenomic, and metabolomic profiles, are urgently required to provide data for risk analyses. The aim of this article is to provide a perspective on the multifactorial derailment of homeostasis leading to the initiation of CRC, which may be explored via multi-omics and Gut-on-Chip analysis to identify much-needed predictive biomarkers.
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Affiliation(s)
- Kyriaki Katsaounou
- Department of Biological Sciences, University of Cyprus, Nicosia 2109, Cyprus; (K.K.); (S.T.)
| | | | - Paris Vogazianos
- Stremble Ventures Ltd., Limassol 4042, Cyprus; (P.V.); (C.B.); (A.A.)
| | - Cameron Brown
- Stremble Ventures Ltd., Limassol 4042, Cyprus; (P.V.); (C.B.); (A.A.)
| | - Marios Stavrou
- Department of Electrical and Computer Engineering, University of Cyprus, Nicosia 2109, Cyprus; (M.S.); (C.A.)
| | - Savvas Teloni
- Department of Biological Sciences, University of Cyprus, Nicosia 2109, Cyprus; (K.K.); (S.T.)
| | - Pantelis Hatzis
- Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center Alexander Fleming, Vari 16672, Greece;
| | - Agapios Agapiou
- Department of Chemistry, University of Cyprus, Nicosia 2109, Cyprus;
| | | | | | | | - Apostolos Zaravinos
- Department of Life Sciences, European University Cyprus, Nicosia 1516, Cyprus;
- Basic and Translational Cancer Research Center, Nicosia 1516, Cyprus
| | - Chrysafis Andreou
- Department of Electrical and Computer Engineering, University of Cyprus, Nicosia 2109, Cyprus; (M.S.); (C.A.)
| | - Athos Antoniades
- Stremble Ventures Ltd., Limassol 4042, Cyprus; (P.V.); (C.B.); (A.A.)
| | | | - Yiorgos Apidianakis
- Department of Biological Sciences, University of Cyprus, Nicosia 2109, Cyprus; (K.K.); (S.T.)
- Correspondence:
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The interplay of pineal hormones and socioeconomic status leading to colorectal cancer disparity. Transl Oncol 2022; 16:101330. [PMID: 34990909 PMCID: PMC8741600 DOI: 10.1016/j.tranon.2021.101330] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Despite increased screening options and state-of-art treatments offered in clinics, racial differences remain in CRC. African Americans (AAs) are disproportionately affected by the disease; the incidence and mortality are higher in AAs than Caucasian Americans (CAs). At the time of diagnosis, AAs more often present with advanced stages and aggressive CRCs, primarily accounting for the racial differences in therapeutic outcomes and mortality. The early incidence of CRC in AAs could be attributed to race-specific gene polymorphisms and lifestyle choices associated with socioeconomic status (SES). Altered melatonin-serotonin signaling, besides the established CRC risk factors (age, diet, obesity, alcoholism, and tobacco use), steered by SES, glucocorticoid, and Vitamin D status in AAs could also account for the early incidence in this racial group. This review focuses on how the lifestyle factors, diet, allelic variants, and altered expression of specific genes could lead to atypical serotonin and melatonin signaling by modulating the synthesis, secretion, and signaling of these pineal hormones in AAs and predisposing them to develop more aggressive CRC earlier than CAs. Crosstalk between gut microbiota and pineal hormones and its impact on CRC pathobiology is addressed from a race-specific perspective. Lastly, the status of melatonin-focused CRC treatments, the need to better understand the perturbed melatonin signaling, and the potential of pineal hormone-directed therapeutic interventions to reduce CRC-associated disparity are discussed.
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Islam MR, Aziz MA, Shahriar M, Islam MS. Polymorphisms in IL-17A Gene and Susceptibility of Colorectal Cancer in Bangladeshi Population: A Case-Control Analysis. Cancer Control 2022; 29:10732748221143879. [PMID: 36458977 PMCID: PMC9720807 DOI: 10.1177/10732748221143879] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 10/25/2022] [Accepted: 11/15/2022] [Indexed: 09/18/2023] Open
Abstract
OBJECTIVE Interleukin-17A (IL-17A) genetic polymorphisms are associated with multiple cancer types, including colorectal cancer (CRC). However, no previous study was performed in the Bangladeshi population to evaluate the association. Our study aimed to find the association between two IL-17A variants (rs10484879 C/A and rs3748067 G/A) and susceptibility of CRC. METHODS AND MATERIALS This retrospective case-control study comprised 292 CRC patients and 288 age, sex, and BMI matched healthy volunteers. Genotyping of both variants was done by the tetra-primer ARMS-PCR method, and the results were analyzed by the SPSS software package (version-25.0). RESULTS Logistic regression analysis indicated that in case of IL-17A rs10484879 polymorphism, AC and AA genotype carriers showed 2.44- and 3.27-times significantly increased risk for CRC development (OR = 2.44, P = .0008 and OR = 3.27, P = .0133, individually). A significant association was also observed for AC + AA genotype (OR = 2.58, P = .0001). Again, over-dominant and allelic model revealed statistically significant link to CRC risk (OR = 2.13, P = .0035 and OR = 2.22, P = .001). For rs3748067 polymorphism, AG and AA genotype carriers showed 2.30- and 2.45-times enhanced risk for CRC (OR = 2.30, P = .005 and OR = 2.45, P = .031). A statistically significant association was also observed for AG + AA genotype (OR = 2.35, P = .001), over-dominant model (OR = 2.05, P = .014), and allelic model (OR = 2.11, P = .0004). CONCLUSION This study highlights that IL-17A rs10484879 and rs3748067 polymorphisms may be associated with CRC development. However, further functional research with larger samples may reveal more statistically significant outcomes.
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Affiliation(s)
- Md. Robiul Islam
- Department of Pharmacy,
University of Asia Pacific, Dhaka,
Bangladesh
- Department of Pharmacy,
State
University of Bangladesh, Dhaka,
Bangladesh
| | - Md. Abdul Aziz
- Department of Pharmacy,
State
University of Bangladesh, Dhaka,
Bangladesh
| | - Mohammad Shahriar
- Department of Pharmacy,
University of Asia Pacific, Dhaka,
Bangladesh
| | - Mohammad Safiqul Islam
- Department of Pharmacy,
Noakhali
Science and Technology University,
Noakhali, Bangladesh
- Laboratory of Pharmacogenomics and
Molecular Biology, Department of Pharmacy, Noakhali Science and Technology
University, Noakhali, Bangladesh
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Stott K, Phillips B, Parry L, May S. Recent advancements in the exploitation of the gut microbiome in the diagnosis and treatment of colorectal cancer. Biosci Rep 2021; 41:BSR20204113. [PMID: 34236075 PMCID: PMC8314433 DOI: 10.1042/bsr20204113] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 07/05/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
Over the last few decades it has been established that the complex interaction between the host and the multitude of organisms that compose the intestinal microbiota plays an important role in human metabolic health and disease. Whilst there is no defined consensus on the composition of a healthy microbiome due to confounding factors such as ethnicity, geographical locations, age and sex, there are undoubtably populations of microbes that are consistently dysregulated in gut diseases including colorectal cancer (CRC). In this review, we discuss the most recent advances in the application of the gut microbiota, not just bacteria, and derived microbial compounds in the diagnosis of CRC and the potential to exploit microbes as novel agents in the management and treatment of CRC. We highlight examples of the microbiota, and their derivatives, that have the potential to become standalone diagnostic tools or be used in combination with current screening techniques to improve sensitivity and specificity for earlier CRC diagnoses and provide a perspective on their potential as biotherapeutics with translatability to clinical trials.
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Affiliation(s)
- Katie J. Stott
- European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff CF24 4HQ, U.K
| | - Bethan Phillips
- European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff CF24 4HQ, U.K
| | - Lee Parry
- European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff CF24 4HQ, U.K
| | - Stephanie May
- CRUK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, U.K
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Chadha S, Kumar A, Srivastava SA, Behl T, Ranjan R. Inulin as a Delivery Vehicle for Targeting Colon-Specific Cancer. Curr Drug Deliv 2021; 17:651-674. [PMID: 32459607 DOI: 10.2174/1567201817666200527133719] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 03/11/2020] [Accepted: 04/01/2020] [Indexed: 12/12/2022]
Abstract
Natural polysaccharides, as well as biopolymers, are now days widely developed for targeting colon cancer using various drug delivery systems. Currently, healing conformations are being explored that can efficiently play a multipurpose role. Owing to the capability of extravagance colonic diseases with the least adverse effects, biopolymers for site specific colon delivery have developed an increased curiosity over the past decades. Inulin (INU) was explored for its probable application as an entrapment material concerning its degradation by enzymes in the colonic microflora and its drug release behavior in a sustained and controlled manner. INU is a polysaccharide and it consists of 2 to 1 linkage having an extensive array of beneficial uses such as a carrier for delivery of therapeutic agents as an indicative/investigative utensil or as a dietary fiber with added well-being aids. In the main, limited research, as well as information, is available on the delivery of therapeutic agents using inulin specifically for colon cancer because of its capability to subsist in the stomach's acidic medium. This exceptional steadiness and robustness properties are exploited in numerous patterns to target drugs securely for the management of colonic cancer, where they effectively act and kills colonic tumor cells easily. In this review article, recent efforts and inulin-based nano-technological approaches for colon cancer targeting are presented and discussed.
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Affiliation(s)
- Swati Chadha
- Department of Pharmaceutics, Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Arun Kumar
- Department of Pharmaceutics, Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | | | - Tapan Behl
- Department of Pharmaceutics, Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Rishu Ranjan
- Department of Pharmaceutics, Chitkara College of Pharmacy, Chitkara University, Punjab, India
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Laparoscopic ileo-cecectomy for ileo-ceco-colic double intussusception due to a cecal adenoma harboring multifocal high grade dysplasia in a 24 years old male: A case report. Int J Surg Case Rep 2020; 77:362-366. [PMID: 33217654 PMCID: PMC7683281 DOI: 10.1016/j.ijscr.2020.10.119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 10/25/2020] [Indexed: 11/23/2022] Open
Abstract
Bowel intussusception is defined as invagination of the intussusceptum into the intussuscepien. Responsible of 1% of all bowel obstructions. Colonic involvement is majorly due to malignant lesions. Colonoscopy has a role in diagnosing the cause and location of leading point, as well as non-operative reduction in selected cases. Oncological surgical resection is the most agreeable definitive treatment method. Introduction Intestinal Intussusception is defined as invagination of the intussusceptum into the intussuscepien, and is responsible of 1% of all bowel obstructions. It is rare in adults and common in children. It is mostly due to organic causes in adults that form lead points. Enteroenteric intussusception is the most common type. Signs and symptoms are more classic in children but nonspecific in adults. Usually diagnosis is made intraoperatively, while abdomino-pelvic CT scan is the best preoperative imaging modality. Intestinal Intussusception in adults, especially when the colon is involved, is best treated by surgical resection. Case presentation A 24 years old previously healthy male with no surgical or documented familial history presenting for severe crampy abdominal pain and distention, obstipation and palpable right lower quadrant abdominal mass. Abdominal Multi-slice CT diagnosed an ileo-colic intussusception without signs of bowel suffering. Laparoscopic ileo-cecetomy. Final Pathology showed a 4 cm cecal tubular adenomatous polyp with multifocal high grade dysplasia. Conclusion Intestinal intussusception in adults is an interesting rare entity that have the interest of general surgeons. Malignant lesions can be lead-points and they form a great counterpart among other colonic lesions. Minimally invasive laparoscopic surgery is gaining interest in management, and surgical resection remains the gold standard while reduction before surgery is debatable and can be considered in selected cases.
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Hull R, Francies FZ, Oyomno M, Dlamini Z. Colorectal Cancer Genetics, Incidence and Risk Factors: In Search for Targeted Therapies. Cancer Manag Res 2020; 12:9869-9882. [PMID: 33116845 PMCID: PMC7553623 DOI: 10.2147/cmar.s251223] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 08/21/2020] [Indexed: 01/04/2023] Open
Abstract
Each year, colorectal cancers (CRCs) affect over a quarter of a million people. The risk of developing CRC in industrialized nations is approximately 5%. When the disease is localised, treatment success rates range from 70-90%; however, advanced CRC has a high mortality rate, consistently ranking in the top three causes of cancer-related deaths. There is a large geographic difference in global distribution, and CRC is predominantly associated with developed countries and a Western lifestyle and diet. As such, the developed world accounts for more than 63% of all cases of CRC. Geographic variations also predict cancer outcomes, which differ between racial and ethnic groups. This variation is due to inequalities in wealth, differences in the exposure to risk factors and barriers to high-quality cancer prevention, early detection and treatment. The aim of this paper was to review CRC in low- and middle-income countries such as South Africa, India, Brazil and China, and compare them with high-income countries such as the United States of America and the United Kingdom. It is important to note that these economically less developed countries, with historically low CRC rates, are experiencing an increased frequency of CRC. The review also discusses biological markers and genetic pathways involved in the development of colorectal cancer. Genes known to be responsible for the most common forms of inherited CRCs have also been identified but more remain to be identified. This would provide more candidate genes to be added to known biomarkers. CRC burden can be controlled through the widespread application of existing knowledge, such as reduced smoking habits, vaccination, early detection and promoting physical activity, accompanied by a healthy diet. An increased understanding of the molecular mechanisms and events underlying colorectal carcinogenesis will enable the development of new targets and therapeutic drugs.
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Affiliation(s)
- Rodney Hull
- SAMRC/UP Precision Prevention & Novel Drug Targets for HIV-Associated Cancers (PPNDTHAC) Extramural Unit, Pan African Cancer Research Institute (PACRI), University of Pretoria, Faculty of Health Sciences, Hatfield 0028, South Africa
| | - Flavia Zita Francies
- SAMRC/UP Precision Prevention & Novel Drug Targets for HIV-Associated Cancers (PPNDTHAC) Extramural Unit, Pan African Cancer Research Institute (PACRI), University of Pretoria, Faculty of Health Sciences, Hatfield 0028, South Africa
| | - Meryl Oyomno
- Department of Surgery, Faculty of Health Sciences, Steve Biko Academic Hospital and the University of Pretoria, Pretoria 0007, South Africa
| | - Zodwa Dlamini
- SAMRC/UP Precision Prevention & Novel Drug Targets for HIV-Associated Cancers (PPNDTHAC) Extramural Unit, Pan African Cancer Research Institute (PACRI), University of Pretoria, Faculty of Health Sciences, Hatfield 0028, South Africa.,Faculty of Health Sciences, School of Clinical Medicine, University of the Witwatersrand, Parktown 2193, South Africa
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Guo P, Tian Z, Kong X, Yang L, Shan X, Dong B, Ding X, Jing X, Jiang C, Jiang N, Yu Y. FadA promotes DNA damage and progression of Fusobacterium nucleatum-induced colorectal cancer through up-regulation of chk2. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2020; 39:202. [PMID: 32993749 PMCID: PMC7523382 DOI: 10.1186/s13046-020-01677-w] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 08/17/2020] [Indexed: 12/14/2022]
Abstract
Background Globally, colorectal cancer (CRC) affects more than 1 million people each year. In addition to non-modifiable and other environmental risk factors, Fusobacterium nucleatum infection has been linked to CRC recently. In this study, we explored mechanisms underlying the role of Fusobacterium nucleatum infection in the progression of CRC in a mouse model. Methods C57BL/6 J-Adenomatous polyposis coli (APC) Min/J mice [APC (Min/+)] were treated with Fusobacterium nucleatum (109 cfu/mL, 0.2 mL/time/day, i.g., 12 weeks), saline, or FadA knockout (FadA−/−) Fusobacterium nucleatum. The number, size, and weight of CRC tumors were determined in isolated tumor masses. The human CRC cell lines HCT29 and HT116 were treated with lentiviral vectors overexpressing chk2 or silencing β-catenin. DNA damage was determined by Comet assay and γH2AX immunofluorescence assay and flow cytometry. The mRNA expression of chk2 was determined by RT-qPCR. Protein expression of FadA, E-cadherin, β-catenin, and chk2 were determined by Western blot analysis. Results Fusobacterium nucleatum treatment promoted DNA damage in CRC in APC (Min/+) mice. Fusobacterium nucleatum also increased the number of CRC cells that were in the S phase of the cell cycle. FadA−/− reduced tumor number, size, and burden in vivo. FadA−/− also reduced DNA damage, cell proliferation, expression of E-cadherin and chk2, and cells in the S phase. Chk2 overexpression elevated DNA damage and tumor growth in APC (Min/+) mice. Conclusions In conclusion, this study provided evidence that Fusobacterium nucleatum induced DNA damage and cell growth in CRC through FadA-dependent activation of the E-cadherin/β-catenin pathway, leading to up-regulation of chk2.
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Affiliation(s)
- Pin Guo
- Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People's Republic of China
| | - Zibin Tian
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, Shandong Province, People's Republic of China
| | - Xinjuan Kong
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, Shandong Province, People's Republic of China
| | - Lin Yang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, Shandong Province, People's Republic of China
| | - Xinzhi Shan
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, Shandong Province, People's Republic of China
| | - Bingzi Dong
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People's Republic of China
| | - Xueli Ding
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, Shandong Province, People's Republic of China
| | - Xue Jing
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, Shandong Province, People's Republic of China
| | - Chen Jiang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, Shandong Province, People's Republic of China
| | - Na Jiang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, Shandong Province, People's Republic of China
| | - Yanan Yu
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266003, Shandong Province, People's Republic of China.
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Mahmood S, MacInnis RJ, Karahalios A, English DR, Lynch BM. Leisure-Time Physical Activity Versus Sedentary Behaviour in Relation to Colorectal Adenoma and Cancer: Are these Two Distinct Risk Factors? CURRENT COLORECTAL CANCER REPORTS 2020. [DOI: 10.1007/s11888-020-00454-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Heisser T, Peng L, Weigl K, Hoffmeister M, Brenner H. Outcomes at follow-up of negative colonoscopy in average risk population: systematic review and meta-analysis. BMJ 2019; 367:l6109. [PMID: 31722884 PMCID: PMC6853024 DOI: 10.1136/bmj.l6109] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/09/2019] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To review and summarise the evidence on the prevalence of colorectal adenomas and cancers at a follow-up screening colonoscopy after negative index colonoscopy, stratified by interval between examinations and by sex. DESIGN Systematic review and meta-analysis of all available studies. DATA SOURCES PubMed, Web of Science, and Embase. Two investigators independently extracted characteristics and results of identified studies and performed standardised quality ratings. ELIGIBILITY CRITERIA Studies assessing the outcome of a follow-up colonoscopy among participants at average risk for colorectal cancer with a negative previous colonoscopy (no adenomas). RESULTS 28 studies were identified, including 22 cohort studies, five cross sectional studies, and one case-control study. Findings for an interval between colonoscopies of one to five, five to 10, and more than 10 years were reported by 17, 16, and three studies, respectively. Summary estimates of prevalences of any neoplasm were 20.7% (95% confidence interval 15.8% to 25.5%), 23.0% (18.0% to 28.0%), and 21.9% (14.9% to 29.0%) for one to five, five to 10, and more than 10 years between colonoscopies. Corresponding summary estimates of prevalences of any advanced neoplasm were 2.8% (2.0% to 3.7%), 3.2% (2.2% to 4.1%), and 7.0% (5.3% to 8.7%). Seven studies also reported findings stratified by sex. Summary estimates stratified by interval and sex were consistently higher for men than for women. CONCLUSIONS Although detection of any neoplasms was observed in more than 20% of participants within five years of a negative screening colonoscopy, detection of advanced neoplasms within 10 years was rare. Our findings suggest that 10 year intervals for colonoscopy screening after a negative colonoscopy, as currently recommended, may be adequate, but more studies are needed to strengthen the empirical basis for pertinent recommendations and to investigate even longer intervals. STUDY REGISTRATION Prospero CRD42019127842.
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Affiliation(s)
- Thomas Heisser
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Le Peng
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Korbinian Weigl
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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Çaykara B, Alsaadoni H, Pençe HH, Pençe S, Yılmaz Aydoğan H, Taştekin D. Investigation of JAM-A (rs790056) and LFA-1 (rs8058823) gene variants in Turkish colorectal cancer patients. TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 30:872-876. [PMID: 31625931 DOI: 10.5152/tjg.2019.19141] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND/AIMS Lymphocyte function-associated antigen 1 (LFA-1) is a transmembrane glycoprotein expressed on the surface of leukocytes and containing the binding domain for junctional adhesion molecule-A (JAM-A). The aim of the present study was to evaluate the effects of JAM-A and LFA-1 variants on the formation of colorectal cancer and metastasis. MATERIALS AND METHODS A total of 82 subjects with colorectal cancer and 67 healthy subjects were studied. DNA was isolated from blood samples, and variations were determined using the polymerase chain reaction and restriction fragment length polymorphism method. RESULTS JAM-A rs790056 CC genotype and C allele were found to be higher in the colorectal cancer group (p<0.05), and approximately 3-fold increased colorectal cancer risk with CC genotype was determined (p=0.029). Haplotype analysis showed that GC haplotype (LFA-1 rs8058823G and JAM-A rs790056C) frequency was significantly higher in the patient group (p=0.041) than in controls. CONCLUSION JAM-A rs790056 variation may be effective in the development of colorectal cancer.
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Affiliation(s)
- Burcu Çaykara
- Department of Physiology, İstanbul Medeniyet University School of Medicine, İstanbul, Turkey
| | - Hani Alsaadoni
- Department of Molecular Medicine, İstanbul University Aziz Sancar Institute of Experimental Medicine (ASDETAE), İstanbul, Turkey
| | - Halime Hanım Pençe
- Department of Medical Biochemistry, University of Health Sciences School of Medicine, İstanbul, Turkey
| | - Sadrettin Pençe
- Department of Physiology, University of Health Sciences School of Medicine, İstanbul, Turkey
| | - Hülya Yılmaz Aydoğan
- Department of Molecular Medicine, İstanbul University Aziz Sancar Institute of Experimental Medicine (ASDETAE), İstanbul, Turkey
| | - Didem Taştekin
- Department of Clinical Oncology, İstanbul University Institute of Oncology, İstanbul, Turkey
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A Review of the Management of Sporadic Colorectal Adenomas in Young People: Is Surveillance Wasted on the Young? Dig Dis Sci 2019; 64:2107-2112. [PMID: 30788685 DOI: 10.1007/s10620-019-05521-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 02/05/2019] [Indexed: 12/25/2022]
Abstract
The national incidence of colorectal cancer is increasing in people younger than 50 years old. Although diagnostic colonoscopy is detecting more sporadic adenomas in young adults, there are no guidelines for post-polypectomy surveillance. The aim of this review was to survey the medical literature on the prevalence of sporadic adenomas in young adults, subsequent risk of metachronous neoplasia, and lastly to provide several concluding recommendations for clinical practice. We found that the prevalence of sporadic adenomas in young adults is greater than initially estimated and dependent upon factors such as colonoscopy indication and age. The incidence of metachronous colorectal neoplasia following polypectomy is unclear but does not appear to be greater than that of older adults. Risk factors for metachronous neoplasia include findings on index colonoscopy, male gender, smoking status, and certain medical comorbidities. Upon finding a colorectal adenoma in a young person, we suggest that a detailed family history be obtained to confirm that it is truly sporadic. Testing adenomas for evidence of Lynch syndrome is low yield. Strategies to inform surveillance intervals may include an assessment of risk factors for metachronous neoplasia, although surveillance intervals shorter than those recommended in current guidelines are not warranted. Future research should focus on obtaining long-term, prospective data on the incidence of metachronous neoplasia in diverse patient populations.
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Roslan NH, Makpol S, Mohd Yusof YA. A Review on Dietary Intervention in Obesity Associated Colon Cancer. Asian Pac J Cancer Prev 2019; 20:1309-1319. [PMID: 31127882 PMCID: PMC6857900 DOI: 10.31557/apjcp.2019.20.5.1309] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Accepted: 04/22/2019] [Indexed: 12/13/2022] Open
Abstract
Background: Colorectal cancer (CRC) is one of the major causes of morbidity and mortality. According to National Cancer Registry, the incidence of colorectal cancer in Peninsular Malaysia increases with age. The incidence is highest among Chinese population but lower among Indians and Malays. Many reviews have suggested that obesity may be associated with a higher risk (>50%) of colorectal cancer. Methods: This study collects a comprehensive data from the literature review available from respective journals on dietary intervention and the chemo-protective mechanisms of a few natural resources in obesity -associated colon cancer based on previous and current studies. Results: In obesity-associated colon cancer, the genes of interest and pathways that are mainly involved include NFκB, P13K/Akt, and MAPK pathways, and FTO, leptin, Cyclin D, MMPs, and STAT3 genes. Dietary modification is one of the alternative steps in early prevention of colon cancer. It has been proposed that the components present in certain foods may have the ability to protect against many diseases including the prevention of cancer. Conclusion: There are many factors that lead to obesity-associated colon cancer and the mechanisms behind it is still undergoing intensive research. This review aims to scrutinize research as well as reviews that have been previously reported on obesity associated colorectal cancer and the beneficial effects of including antioxidants-rich foods such as vegetables and fruits in the diet to reduce the risk of obesity associated colorectal cancer.
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Affiliation(s)
- N H Roslan
- Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Bandar Tun Razak, Cheras, Kuala Lumpur, Malaysia.
| | - S Makpol
- Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Bandar Tun Razak, Cheras, Kuala Lumpur, Malaysia.
| | - Y A Mohd Yusof
- Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Bandar Tun Razak, Cheras, Kuala Lumpur, Malaysia.
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Kim NH, Jung YS, Yang HJ, Park SK, Park JH, Park DI, Sohn CI. Prevalence of and Risk Factors for Colorectal Neoplasia in Asymptomatic Young Adults (20-39 Years Old). Clin Gastroenterol Hepatol 2019; 17:115-122. [PMID: 30025922 DOI: 10.1016/j.cgh.2018.07.011] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Revised: 06/30/2018] [Accepted: 07/04/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS The incidence of colorectal cancer is increasing among persons 50 years old or younger. However, data on the epidemiology of young-onset colorectal neoplasia (CRN) are limited. Although some studies have investigated the epidemiology of CRN in persons younger than 50 years, most have focused on persons 40 years or older. We evaluated the prevalence of and risk factors for CRN in adults younger than 40 years. METHODS We performed a cross-sectional analysis of 72,356 asymptomatic individuals, 20-39 years old, who underwent colonoscopies as participants in the Kangbuk Samsung Health Study in South Korea, from August 2004 through December 2015. Data on medical history and health-related behavior were collected from self-administered questionnaires. Patients were divided into groups based on age (20-29 years, n = 7340 or 30-39 years, n = 65,016), and χ2 tests were used to compare categorical variables between groups. A multivariate logistic regression model was used to assess the risk factors for overall and advanced CRN. RESULTS The prevalence of overall CRN in group of 20-29 years was 5.9% and in the group of 30-39 years was 9.5% (P < .001); prevalence values for advanced CRN were 0.6% and 0.9%, respectively (P = .005). In the group of 30-39 years, age, smoking, alcohol intake, obesity, and abdominal obesity were independent risk factors for overall and advanced CRN. Additionally, male sex and metabolic syndrome were independent risk factors for overall CRN, whereas regular exercise reduced risk of overall CRN. Even in the 20-29 years group, obesity, abdominal obesity, and increased levels of triglycerides were independent risk factors for overall and advanced CRN, whereas age, increased blood pressure, and increased fasting blood glucose level were independent risk factors for overall CRN. CONCLUSION In a retrospective analysis of 72,356 asymptomatic persons under 40 years of age evaluated by colonoscopy in Korea, we found modifiable factors, such as smoking, alcohol intake, obesity, and metabolic syndrome, to be significant risk factors for CRN-even in persons of 20-39 years old. Colorectal cancer screening strategies should consider these risk factors.
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Affiliation(s)
- Nam Hee Kim
- Preventive Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
| | - Hyo-Joon Yang
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Soo-Kyung Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung Ho Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Il Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chong Il Sohn
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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18
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Kim NH, Jung YS, Park JH, Park DI, Sohn CI. Risk of developing metachronous advanced colorectal neoplasia after colonoscopic polypectomy in patients aged 30 to 39 and 40 to 49 years. Gastrointest Endosc 2018; 88:715-723. [PMID: 29857003 DOI: 10.1016/j.gie.2018.05.018] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 05/19/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Current guidelines define postpolypectomy surveillance intervals in patients aged ≥50 years. The risk of metachronous colorectal neoplasia (CRN) and the optimal postpolypectomy surveillance interval in patients aged <50 years remain unclear. We compared the risk of metachronous CRN in patients aged 30 to 39, 40 to 49, and ≥50 years. METHODS We studied patients who underwent ≥1 adenoma removal between 2010 and 2014 and follow-up colonoscopic surveillance until 2017. RESULTS Among 10,014 patients studied, 3242, 4606, and 2166 were 30 to 39, 40 to 49, and ≥50 years old, respectively. After high-risk adenoma removal, the 3-year risk of metachronous advanced CRN (ACRN) in patients aged 30 to 39 and 40 to 49 years was lower than in patients ≥50 years old (1.9% and 3.6% vs 8.1%, respectively; P < .001 and .008). After low-risk adenoma removal, the 5-year risk of metachronous ACRN in patients aged 30 to 39 and 40 to 49 years was lower than in patients ≥50 years old (2.8% and 3.3% vs 5.9%, respectively; P = .010 and .031). The risk of metachronous ACRN or ≥3 adenomas in patients aged 30 to 39 years was significantly lower than in patients aged 40 to 49 years. Age remained significantly associated with the risk of metachronous ACRN despite adjustments for potential confounders. CONCLUSIONS The risk of metachronous ACRN was lower in patients aged <50 years than in those aged ≥50 years; thus, the postpolypectomy surveillance interval may be extendable to >3 and 5 years in high-risk and low-risk adenoma groups, respectively, in patients aged <50 years.
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Affiliation(s)
- Nam Hee Kim
- Preventive Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung Ho Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Il Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chong Il Sohn
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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Abstract
BACKGROUND Although adenoma prevalence is lower in younger people compared with screening-aged adults 50 years old and above, there is no adjustment recommendation for the target adenoma detection rate (ADR) in young people. Herein, we estimated a different target ADR for adults below 50 years old based on screening colonoscopy findings. MATERIALS AND METHODS Asymptomatic, average-risk adults below 50 years old who underwent screening colonoscopy were enrolled at 12 endoscopy centers in Korea between February 2006 and March 2012. Screening colonoscopies were stratified into low or high ADR groups with ADR levels of 20% and 25%, respectively. RESULTS The ADRs from 12 endoscopy centers ranged from 12.1% to 43.8% (median ADR, 24.1%) based on 5272 young adults receiving screening colonoscopies. Using 20% as an ADR level, the risks for metachronous adenoma and advanced adenoma were significantly higher in the low ADR group than the high ADR group (35.4% vs. 25.7%, P<0.001; 8.3% vs. 3.7%, P=0.001, respectively). However, using ADR level of 25%, the risk for metachronous neoplasia was similar in the high and low ADR groups in young adults according to screening colonoscopy. In subgroup analysis, similar findings were found in males, but not in females. CONCLUSIONS Optimal target ADR may be different between younger and older populations, and the adoption of a 20% target ADR could be used as a performance indicator for young populations.
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Kim HG, Cho YS, Cha JM, Shin JE, Kim KO, Yang HJ, Koo HS, Joo YE, Boo SJ. Risk of metachronous neoplasia on surveillance colonoscopy in young patients with colorectal neoplasia. Gastrointest Endosc 2018; 87:666-673. [PMID: 28619245 DOI: 10.1016/j.gie.2017.05.053] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Accepted: 05/24/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Few prior reports exist that address the appropriate colonoscopy surveillance interval for individuals <50 years old. We compared the risk of metachronous neoplasia between younger (20-49 years) and older (50-54 years) cohorts. METHODS This multicenter retrospective cohort study compared the incidence of metachronous neoplasia in younger and older cohorts according to baseline risk stratification. Subjects were eligible if they underwent their first colonoscopy between June 2006 and May 2010 and had at least 1 or more surveillance colonoscopy up to June 2015. RESULTS Among a total of 10,477 subjects who underwent baseline colonoscopy, 9722 were eligible after excluding 755 subjects. Of those 9722 subjects, 43% underwent surveillance colonoscopy. In the baseline high-risk adenoma group (n = 840), the 3-year risk of metachronous advanced neoplasia was 10.7% in the younger patients on screening colonoscopy and 8.9% in the older patients (P > .1). In the baseline low-risk adenoma group (n = 1869), the 5-year risk of metachronous advanced neoplasia was 4.9% in the younger patients on screening colonoscopy and 5.1% in the older patients (P > .1). Similarly, in the baseline no neoplasia group (n = 7013), the 5-year risk of metachronous advanced neoplasia was 4.1% in the younger patients on screening colonoscopy and 5.6% in the older patients (P > .1). CONCLUSIONS Considering the similar risk of metachronous advanced neoplasia in younger and older individuals, we suggest a 3-year surveillance interval for high-risk adenoma and a 5-year surveillance interval for low-risk adenoma in young individuals without a strong family history.
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Affiliation(s)
- Hyun Gun Kim
- Department of Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Young-Seok Cho
- Department of Medicine, Catholic University College of Medicine, Seoul, Korea
| | - Jae Myung Cha
- Department of Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jeong Eun Shin
- Department of Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Kyeong Ok Kim
- Department of Internal, Yeungnam University College of Medicine, Daegu, Korea
| | - Hyo-Joon Yang
- Department of Medicine, Kangbuk Samsung Hospital, Seoul, Korea
| | - Hoon Sup Koo
- Department of Medicine, Konyang University College of Medicine, Daejeon, Korea
| | - Young-Eun Joo
- Department of Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Sun-Jin Boo
- Department of Medicine, Jeju National University School of Medicine, Jeju, Korea
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Challa S, Ajumeera R, Venna N. Phytoestrogens as a Natural Source for the Possible Colon Cancer Treatment. ANTICANCER PLANTS: MECHANISMS AND MOLECULAR INTERACTIONS 2018:259-281. [DOI: 10.1007/978-981-10-8417-1_11] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Daly PE, Samiee S, Cino M, Gryfe R, Pollett A, Ng A, Constine LS, Hodgson DC. High prevalence of adenomatous colorectal polyps in young cancer survivors treated with abdominal radiation therapy: results of a prospective trial. Gut 2017; 66:1797-1801. [PMID: 27411369 DOI: 10.1136/gutjnl-2016-311501] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Revised: 06/14/2016] [Accepted: 06/15/2016] [Indexed: 01/08/2023]
Abstract
OBJECTIVE Cancer survivors treated with abdominal/pelvic radiation therapy (ART) have increased the risks of colorectal cancer (CRC), although evidence supporting early CRC screening for these patients is lacking. We sought to determine whether there is an elevated prevalence of adenomatous colorectal polyps in young survivors prior to the age when screening would be routinely recommended. DESIGN We conducted a prospective study of early colonoscopic screening in cancer survivors aged 35-49 who had received ART ≥10 years previously. The planned sample size was based on prior studies reporting a prevalence of adenomatous polyps of approximately 20% among the average-risk population ≥50 years of age, in contrast to ≤10% among those average-risk people aged 40-50 years, for whom screening is not routinely recommended. RESULTS Colonoscopy was performed in 54 survivors, at a median age of 45 years (range 36-49) and after median interval from radiation treatment of 19 years (10.6-43.5). Forty-nine polyps were detected in 24 patients, with 15 patients (27.8%; 95% CI 17.6% to 40.9%) having potentially precancerous polyps. Fifty-three per cent of polyps were within or at the edge of the prior ART fields. CONCLUSIONS Young survivors treated with ART have a polyp prevalence comparable with the average-risk population aged ≥50 years and substantially higher than previously reported for the average-risk population aged 40-50 years. These findings lend support to the early initiation of screening in these survivors. CLINICAL TRIAL REGISTRATION NUMBER NCT00982059; results.
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Affiliation(s)
- Patricia E Daly
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Sara Samiee
- Hematology Oncology and BMT Research Centre, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Maria Cino
- Department of Gastroenterology, Toronto Western Hospital, Toronto, Ontario, Canada
| | - Robert Gryfe
- Department of Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Aaron Pollett
- Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Andrea Ng
- Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA
| | - Louis S Constine
- Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York, USA
| | - David C Hodgson
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
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Skyrud KD, Myklebust TÅ, Bray F, Eriksen MT, de Lange T, Larsen IK, Møller B. How Many Deaths from Colorectal Cancer Can Be Prevented by 2030? A Scenario-Based Quantification of Risk Factor Modification, Screening, and Treatment in Norway. Cancer Epidemiol Biomarkers Prev 2017; 26:1420-1426. [PMID: 28626069 DOI: 10.1158/1055-9965.epi-17-0265] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Revised: 05/24/2017] [Accepted: 06/06/2017] [Indexed: 11/16/2022] Open
Abstract
Background: Colorectal cancer mortality can be reduced through risk factor modification (adherence to lifestyle recommendations), screening, and improved treatment. This study estimated the potential of these three strategies to modify colorectal cancer mortality rates in Norway.Methods: The potential reduction in colorectal cancer mortality due to risk factor modification was estimated using the software Prevent, assuming that 50% of the population in Norway-who do not adhere to the various recommendations concerning prevention of smoking, physical activity, body weight, and intake of alcohol, red/processed meat, and fiber-started to follow the recommendations. The impact of screening was quantified assuming implementation of national flexible sigmoidoscopy screening with 50% attendance. The reduction in colorectal cancer mortality due to improved treatment was calculated assuming that 50% of the linear (positive) trend in colorectal cancer survival would continue to persist in future years.Results: Risk factor modification would decrease colorectal cancer mortality by 11% (corresponding to 227 prevented deaths: 142 men, 85 women) by 2030. Screening and improved treatment in Norway would reduce colorectal cancer mortality by 7% (149 prevented deaths) and 12% (268 prevented deaths), respectively, by 2030. Overall, the combined effect of all three strategies would reduce colorectal cancer mortality by 27% (604 prevented deaths) by 2030.Conclusions: Risk factor modification, screening, and treatment all have considerable potential to reduce colorectal cancer mortality by 2030, with the largest potential reduction observed for improved treatment and risk factor modification.Impact: The estimation of these health impact measures provides useful information that can be applied in public health decision-making. Cancer Epidemiol Biomarkers Prev; 26(9); 1420-6. ©2017 AACR.
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Affiliation(s)
- Katrine Damgaard Skyrud
- Department of Registration, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Majorstuen, Oslo, Norway.
| | - Tor Åge Myklebust
- Department of Registration, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Majorstuen, Oslo, Norway
| | - Freddie Bray
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - Morten Tandberg Eriksen
- Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Thomas de Lange
- Department of Registration, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Majorstuen, Oslo, Norway
| | - Inger Kristin Larsen
- Department of Registration, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Majorstuen, Oslo, Norway
| | - Bjørn Møller
- Department of Registration, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Majorstuen, Oslo, Norway
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Khan AA, Khan Z, Malik A, Kalam MA, Cash P, Ashraf MT, Alshamsan A. Colorectal cancer-inflammatory bowel disease nexus and felony of Escherichia coli. Life Sci 2017; 180:60-67. [PMID: 28506682 DOI: 10.1016/j.lfs.2017.05.016] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2017] [Revised: 04/24/2017] [Accepted: 05/12/2017] [Indexed: 12/19/2022]
Abstract
Colorectal cancer (CRC) has a multifactorial etiology. Although the exact cause of CRC is still elusive, recent studies have indicated microbial involvement in its etiology. Escherichia coli has emerged as an important factor in CRC development since the bacterium can cause changes in the gut that lead to cancerous transformation. A number of studies indicate that chronic inflammation induced by microorganisms, including E. coli, during inflammatory bowel disease (IBD) predisposes an individual to CRC. The evidence that support the role of E. coli in the etiology of CRC, through IBD, is not limited only to chronic inflammation. The growth of E. coli as an intracellular pathogen during IBD and CRC enable the bacteria to modulate the host cell cycle, induce DNA damage and accumulate mutations. These are some of the contributing factors behind the etiology of CRC. The present article considers the current status of the involvement of E. coli, through IBD, in the etiology of CRC. We discuss how intracellular E. coli infection can cause changes in the gut that can eventually lead to cellular transformation. In addition, the recent management strategies that target E. coli for prevention of CRC are also discussed.
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Affiliation(s)
- Abdul Arif Khan
- Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, PO Box 2457, King Saud University, Riyadh 11451, Saudi Arabia.
| | - Zakir Khan
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Baverly Blvd., Los Angeles, CA 90048, USA
| | - Abdul Malik
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11451, Saudi Arabia
| | - Mohd Abul Kalam
- Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, PO Box 2457, King Saud University, Riyadh 11451, Saudi Arabia
| | - Phillip Cash
- The Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom
| | | | - Aws Alshamsan
- Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, PO Box 2457, King Saud University, Riyadh 11451, Saudi Arabia; King Abdullah Institute for Nanotechnology, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia
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Wang H, Chen Z, Chang H, Mu X, Deng W, Yuan Z, Yao F, Liu Y, Mai R, Wu B. Expression of glia maturation factor γ is associated with colorectal cancer metastasis and its downregulation suppresses colorectal cancer cell migration and invasion in vitro. Oncol Rep 2017; 37:929-936. [PMID: 28075454 DOI: 10.3892/or.2017.5361] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Accepted: 11/11/2016] [Indexed: 11/05/2022] Open
Abstract
Glia maturation factor γ (GMFG) functions to reorganize the actin cytoskeleton and appears to play a causative role in cell migration and adherence. The present study assessed GMFG expression in colorectal cancer cells and tissue specimens and then explored the role of GMFG in colorectal cancer progression in vitro. GMFG protein was highly expressed in colorectal cancer tissues and a metastatic colon cancer cell line. Knockdown of GMFG expression using GMFG siRNA or anti-GMFG antibody decreased the capacity of colon cancer LoVo cell migration and invasion in vitro, while recombinant GMFG treatment induced LoVo cell migration. Furthermore, GMFG knockdown also decreased expression of MMP2 protein and reversed epithelial-mesenchymal transition (EMT) phenotypes in LoVo cells. Co-culture of LoVo cells with human umbilical vein endothelial cells (HUVECs) and exogenous GMFG treatment promoted LoVo cell migration and invasion. The data from the present study indicate that GMFG should be further evaluated as a biomarker for detection of colorectal cancer metastasis and that the targeting of GMFG expression or function could be a novel strategy in the future control of colorectal cancer.
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Affiliation(s)
- Huili Wang
- Research Center of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510000, P.R. China
| | - Zhijiang Chen
- Pediatric Center of Zhujiang Hospital, Southern Medical University, Guangzhou 510000, P.R. China
| | - Hongen Chang
- Department of Neurology, Liuzhou Hospital of Traditional Chinese Medicine, Guangxi 545001, P.R. China
| | - Xiaoping Mu
- Guangdong Women and Children Hospital, Guangzhou 510000, P.R. China
| | - Wenyu Deng
- Guangdong Women and Children Hospital, Guangzhou 510000, P.R. China
| | - Zhaohu Yuan
- Department of Blood Transfusion Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510000, P.R. China
| | - Fang Yao
- Research Center of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510000, P.R. China
| | - Yan Liu
- Guangdong Women and Children Hospital, Guangzhou 510000, P.R. China
| | - Rongjia Mai
- Guangdong Women and Children Hospital, Guangzhou 510000, P.R. China
| | - Bingyi Wu
- Research Center of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510000, P.R. China
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Kwak JY, Kim KM, Yang HJ, Yu KJ, Lee JG, Jeong YO, Shim SG. Prevalence of colorectal adenomas in asymptomatic young adults: a window to early intervention? Scand J Gastroenterol 2016; 51:731-8. [PMID: 26863602 DOI: 10.3109/00365521.2015.1130163] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The prevalence of colorectal adenoma is increasing in the average-risk population. However, little research is available on colorectal adenoma in young adults under age 40. The aim of this study was to investigate the prevalence and risk factors of colorectal adenoma in 20- to 39-year-old adults. METHODS We evaluated 4286 asymptomatic young adults aged 20 to 39 years who underwent first colonoscopy screening as part of an employer-provided health wellness programme at the Health Promotion Centre of Samsung Changwon Hospital, Korea from January 2011 to December 2013. Logistic regression modelling was used to identify risk factors for colorectal adenoma in asymptomatic young adults. RESULTS The prevalence of colorectal adenoma and advanced adenoma was 11.6% (497/4286) and 0.9% (39/4286), respectively. By age group, the prevalence of colorectal adenoma was 5.4% (33/608) in participants aged 20 to 29 years and 12.6% (464/3678) in participants aged 30 to 39. Colorectal adenoma was found in 13.1% (403/3072) of men and 7.7% (94/1214) of women. Increased risk of colorectal adenoma was associated with age over 30 years (OR, 2.37; 95% CI, 1.64-3.42), current smoker status (OR, 1.48; 95% CI, 1.14-1.91), and alcohol consumption (OR, 1.29; 95% CI, 1.03-1.63). CONCLUSIONS Our findings indicate that even if the prevalence of colorectal adenoma was low in young adults aged 20 to 39, being over 30, cigarette smoking, and alcohol consumption can affect young adults who have no other CRC risks.
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Affiliation(s)
- Ji Yeong Kwak
- a Health Promotion Centre, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine , Changwon , Korea
| | - Kwang Min Kim
- b Department of Medicine , Samsung Changwon Hospital, Sungkyunkwan University School of Medicine , Changwon , Korea
| | - Hae Jin Yang
- c Department of Medicine , Hanheart Hospital , Changwon , Korea
| | - Kil Jong Yu
- b Department of Medicine , Samsung Changwon Hospital, Sungkyunkwan University School of Medicine , Changwon , Korea
| | - Jae Gon Lee
- b Department of Medicine , Samsung Changwon Hospital, Sungkyunkwan University School of Medicine , Changwon , Korea
| | - Yeon Oh Jeong
- b Department of Medicine , Samsung Changwon Hospital, Sungkyunkwan University School of Medicine , Changwon , Korea
| | - Sang Goon Shim
- b Department of Medicine , Samsung Changwon Hospital, Sungkyunkwan University School of Medicine , Changwon , Korea
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Leshno A, Moshkowitz M, David M, Galazan L, Neugut AI, Arber N, Santo E. Prevalence of colorectal neoplasms in young, average risk individuals: A turning tide between East and West. World J Gastroenterol 2016; 22:7365-7372. [PMID: 27621582 PMCID: PMC4997636 DOI: 10.3748/wjg.v22.i32.7365] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 05/11/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the prevalence of colorectal neoplasia in average risk persons 40-59 years of age in Israel and to compare the results with other populations.
METHODS We reviewed the results of asymptomatic average-risk subjects, aged 40 to 59 years, undergoing their first screening colonoscopy between April 1994 and January 2014. The detection rates of adenoma, advanced adenoma (AA) and colorectal cancer (CRC) were determined in the 40’s and 50’s age groups by gender. The prevalence of lesions was compared between age groups. After meticulous review of the literature, these results were compared to published studies addressing the prevalence of colorectal neoplasia in similar patient groups, in a variety of geographical locations.
RESULTS We included first screening colonoscopy results of 1750 individuals. The prevalence of adenomas, AA and CRC was 8.3%, 1.0% and 0.2% in the 40-49 age group and 13.7%, 2.4% and 0.2% in the 50-59 age group, respectively. Age-dependent differences in adenoma and AA rates were significant only among men (P < 0.005). Literature review disclosed 17 relevant studies. As expected, in both Asian and Western populations, the risks for overall adenoma and advanced adenoma was significantly higher in the 50's age group as compared to the 40's age group in a similar fashion. The result of the current study were similar to previous studies on Western populations. A substantially higher rate of adenoma, was observed in studies conducted among Asian populations in both age groups.
CONCLUSION The higher rate of colorectal neoplasia in Asian populations requires further investigation and reconsideration as to the starting age of screening in that population.
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Bayar B, Yılmaz KB, Akıncı M, Şahin A, Kulaçoğlu H. An evaluation of treatment results of emergency versus elective surgery in colorectal cancer patients. ULUSAL CERRAHI DERGISI 2015; 32:11-7. [PMID: 26985154 DOI: 10.5152/ucd.2015.2969] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/31/2014] [Accepted: 02/16/2015] [Indexed: 12/28/2022]
Abstract
OBJECTIVE Colorectal cancer is still one of the most common causes of cancer related deaths in the world despite improvements in diagnosis and treatment modalities, and application of community-based screening methods. Symptoms of colorectal cancer are non-specific and usually manifest following local progression. A number of patients with advanced stage colorectal cancer present to emergency departments with obstruction as the first sign of disease without any previous symptoms. This presentation is an indication for emergency surgery that has a high rate of morbidity and mortality. In this study, we aimed to determine the factors associated with early diagnosis and survival by comparing postoperative results of colorectal cancer patients who underwent surgery under emergency or elective situation. MATERIAL AND METHODS Files of colorectal patients treated between 2009-2013 were retrospectively analyzed. Data on patient age, gender, operation type, intraoperative results, length of hospital stay, co-morbidities, postoperative complications and pathological results were evaluated and compared. RESULTS There was no statistical difference between groups in terms of age, gender, and pathology results (p>0.05). The difference between groups in terms of postoperative length of hospital stay, presence of co-morbid diseases, pathological stage, and postoperative complications was statistically significant (p<0.05). Length of hospital stay, advanced stage on admission, complications such as surgical site infection, evisceration, and anastomosis leakage rates were higher in patients in the emergency surgery group. CONCLUSION Risk groups should be determined in order to diagnose colorectal cancer patients at an early stage while they are still asymptomatic, and this information should be incorporated into effective screening programs. This approach will be beneficial to treatment outcomes, complication rates, length of hospital stay, and survival and treatment results.
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Affiliation(s)
- Bahattin Bayar
- Clinic of General Surgery, Muş State Hospital, Muş, Turkey
| | - Kerim Bora Yılmaz
- Clinic of General Surgery, Ankara Dışkapı Training and Research Hospital, Ankara, Turkey
| | - Melih Akıncı
- Clinic of General Surgery, Ankara Dışkapı Training and Research Hospital, Ankara, Turkey
| | - Alpaslan Şahin
- Clinic of General Surgery, Konya Training and Research Hospital, Konya, Turkey
| | - Hakan Kulaçoğlu
- Clinic of General Surgery, Ankara Dışkapı Training and Research Hospital, Ankara, Turkey
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29
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Charepalli V, Reddivari L, Radhakrishnan S, Vadde R, Agarwal R, Vanamala JKP. Anthocyanin-containing purple-fleshed potatoes suppress colon tumorigenesis via elimination of colon cancer stem cells. J Nutr Biochem 2015; 26:1641-9. [PMID: 26383537 DOI: 10.1016/j.jnutbio.2015.08.005] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Revised: 07/15/2015] [Accepted: 08/05/2015] [Indexed: 12/15/2022]
Abstract
Cancer stem cells (CSCs) are shown to be responsible for initiation and progression of tumors in a variety of cancers. We previously showed that anthocyanin-containing baked purple-fleshed potato (PP) extracts (PA) suppressed early and advanced human colon cancer cell proliferation and induced apoptosis, but their effect on colon CSCs is not known. Considering the evidence of bioactive compounds, such as anthocyanins, against cancers, there is a critical need to study anticancer activity of PP, a global food crop, against colon CSCs. Thus, isolated colon CSCs (positive for CD44, CD133 and ALDH1b1 markers) with functioning p53 and shRNA-attenuated p53 were treated with PA at 5.0 μg/ml. Effects of baked PP (20% wt/wt) against colon CSCs were also tested in vivo in mice with azoxymethane-induced colon tumorigenesis. Effects of PA/PP were compared to positive control sulindac. In vitro, PA suppressed proliferation and elevated apoptosis in a p53-independent manner in colon CSCs. PA, but not sulindac, suppressed levels of Wnt pathway effector β-catenin (a critical regulator of CSC proliferation) and its downstream proteins (c-Myc and cyclin D1) and elevated Bax and cytochrome c, proteins-mediating mitochondrial apoptosis. In vivo, PP reduced the number of crypts containing cells with nuclear β-catenin (an indicator of colon CSCs) via induction of apoptosis and suppressed tumor incidence similar to that of sulindac. Combined, our data suggest that PP may contribute to reduced colon CSCs number and tumor incidence in vivo via suppression of Wnt/β-catenin signaling and elevation of mitochondria-mediated apoptosis.
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Affiliation(s)
- Venkata Charepalli
- Department of Food Science, The Pennsylvania State University, University Park, PA 16802, USA
| | - Lavanya Reddivari
- Department of Plant Science, The Pennsylvania State University, University Park, PA 16802, USA
| | - Sridhar Radhakrishnan
- Department of Food Science, The Pennsylvania State University, University Park, PA 16802, USA
| | - Ramakrishna Vadde
- Department of Food Science, The Pennsylvania State University, University Park, PA 16802, USA; Department of Biotechnology & Bioinformatics, Yogi Vemana University, Kadapa, 516003 AP, India
| | - Rajesh Agarwal
- Pharmaceutical Sciences, University of Colorado, Aurora, CO 80045, USA
| | - Jairam K P Vanamala
- Department of Food Science, The Pennsylvania State University, University Park, PA 16802, USA; The Pennsylvania State Hershey Cancer Institute, Penn State Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
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30
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18 F-FDG PET/contrast enhanced CT in the standard surveillance of high risk colorectal cancer patients. Eur J Radiol 2014; 83:2224-2230. [DOI: 10.1016/j.ejrad.2014.08.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2014] [Revised: 08/16/2014] [Accepted: 08/27/2014] [Indexed: 12/16/2022]
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A comparative overview of general risk factors associated with the incidence of colorectal cancer. Tumour Biol 2013; 34:2469-76. [PMID: 23832537 DOI: 10.1007/s13277-013-0876-y] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Accepted: 05/16/2013] [Indexed: 12/14/2022] Open
Abstract
Cancers found in colorectal region remain largely localized to the large intestine and rectum. They are derived from the epithelium and are considered to be among the most frequently detected cancers. They are known to occur in approximately 5 % population of the Western world. After metastasis, a patient's 5-year postsurgical survival chances unfortunately fall from 90 to 10 % or even less. Adenocarcinoma, the most common cell type of colon cancer, alone constitutes 95 % of the cases. Lymphoma and squamous cell carcinoma can also be found in some cases. Because 5 % of persons are predisposed to development of colorectal cancer, this disease has often been addressed as an important public health issue. Factors that are known in particular to increase a person's risk to develop this cancer are as follows: an individual's age, dietary habits, any complaint of obesity, diabetes, previous history of cancer or intestinal polyps, personal habit of alcohol consumption and smoking, family history of colon cancer, race, sex, and ethnicity. Since the risk of colorectal cancer is increasing steadily in Kashmir, India, like in some other corners of Asia, exhaustive efforts are being made to find the association of above given and other risk factors with the development of this gastrointestinal tract cancer. Adoption of Western life style, diet mimicry, together with a habit of having physically inactive life style and consumption of red meat in particular can be blamed as being active players to a considerable extent.
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32
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Ling W, Mooney L, Zhao M, Nielsen S, Torrington M, Miotto K. Selective review and commentary on emerging pharmacotherapies for opioid addiction. Subst Abuse Rehabil 2011; 2:181-8. [PMID: 24474855 PMCID: PMC3846315 DOI: 10.2147/sar.s22782] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Pharmacotherapies for opioid addiction under active development in the US include lofexidine (primarily for managing withdrawal symptoms) and Probuphine®, a distinctive mode of delivering buprenorphine for six months, thus relieving patients, clinicians, and regulatory personnel from most concerns about diversion, misuse, and unintended exposure in children. In addition, two recently approved formulations of previously proven medications are in early phases of implementation. The sublingual film form of buprenorphine + naloxone (Suboxone®) provides a less divertible, more quickly administered, more child-proof version than the buprenorphine + naloxone sublingual tablet. The injectable depot form of naltrexone (Vivitrol®) ensures consistent opioid receptor blockade for one month between administrations, removing concerns about medication compliance. The clinical implications of these developments have attracted increasing attention from clinicians and policymakers in the US and around the world, especially given that human immunodeficiency virus/acquired immunodeficiency syndrome and other infectious diseases are recognized as companions to opioid addiction, commanding more efforts to reduce opioid addiction. While research and practice improvement efforts continue, reluctance to adopt new medications and procedures can be expected, especially considerations in the regulatory process and in the course of implementation. Best practices and improved outcomes will ultimately emerge from continued development efforts that reflect input from many quarters.
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Affiliation(s)
- Walter Ling
- Integrated Substance Abuse Programs, University of California, Los Angeles, CA, USA
| | - Larissa Mooney
- Integrated Substance Abuse Programs, University of California, Los Angeles, CA, USA
| | - Min Zhao
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Suzanne Nielsen
- Integrated Substance Abuse Programs, University of California, Los Angeles, CA, USA
| | - Matthew Torrington
- Integrated Substance Abuse Programs, University of California, Los Angeles, CA, USA
| | - Karen Miotto
- Integrated Substance Abuse Programs, University of California, Los Angeles, CA, USA
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Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg 2011; 22:191-7. [PMID: 21037809 DOI: 10.1055/s-0029-1242458] [Citation(s) in RCA: 1380] [Impact Index Per Article: 98.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In this article, the incidence, mortality, and survival rates for colorectal cancer are reviewed, with attention paid to regional variations and changes over time. A concise overview of known risk factors associated with colorectal cancer is provided, including familial and hereditary factors, as well as environmental lifestyle-related risk factors such as physical inactivity, obesity, smoking, and alcohol consumption.
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Affiliation(s)
- Fatima A Haggar
- Department of Surgery, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
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34
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Day LW, Espey DK, Madden E, Segal M, Terdiman JP. Screening prevalence and incidence of colorectal cancer among American Indian/Alaskan natives in the Indian Health Service. Dig Dis Sci 2011; 56:2104-13. [PMID: 21234688 PMCID: PMC3112488 DOI: 10.1007/s10620-010-1528-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2010] [Accepted: 12/09/2010] [Indexed: 12/14/2022]
Abstract
BACKGROUND Studies on colorectal cancer (CRC) screening and incidence among American Indian/Alaska Natives (AI/AN) are few. AIMS Our aim was to determine CRC screening prevalence and to calculate CRC incidence among AI/AN receiving care within the Indian Health Service (IHS). METHODS A retrospective cohort study of AI/AN who utilized IHS from 1996 to 2004. AI/AN who were average-risk for CRC and received primary care within IHS were identified by searching the IHS Resource Patient Management System for selected ICD-9/CPT codes (n = 142,051). CRC screening prevalence was calculated and predictors of screening were determined for this group. CRC incidence rates were ascertained for the entire AI/AN population ages 50-80 who received IHS medical care between 1996 and 2004 (n = 283,717). RESULTS CRC screening was performed in 4.0% of average-risk AI/AN. CRC screening was more common among women than men (RR = 1.6, 95% CI 1.4-1.7) and among AI/AN living in the Alaska region compared to the Pacific Coast region (RR = 2.5, 95% CI 2.2-2.8) while patients living in the Northern Plains (RR = 0.4, 95% CI 0.3-0.4) were less likely to have been screened. CRC screening was less common among patients with a greater number of primary care visits. The age-adjusted CRC incidence among AI/AN ages 50-80 was 227 cancers per 100,000 person-years. CONCLUSIONS CRC was common among AI/AN receiving medical care within IHS. However, CRC screening prevalence was far lower than has been reported for the U.S. population.
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Affiliation(s)
- Lukejohn W Day
- Division of Gastroenterology, San Francisco General Hospital (3D), 1001 Potrero Avenue, San Francisco, CA 94110, USA.
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Middeldorp A, Jagmohan-Changur SC, van der Klift HM, van Puijenbroek M, Houwing-Duistermaat JJ, Webb E, Houlston R, Tops C, Vasen HFA, Devilee P, Morreau H, van Wezel T, Wijnen J. Comprehensive genetic analysis of seven large families with mismatch repair proficient colorectal cancer. Genes Chromosomes Cancer 2010; 49:539-48. [PMID: 20222047 DOI: 10.1002/gcc.20763] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Approximately 40% of colorectal cancer (CRC) families with a diagnosis of hereditary nonpolyposis CRC on the basis of clinical criteria are not a consequence of mismatch repair (MMR) deficiency. Such families provide supporting evidence for the existence of a hitherto unidentified highly penetrant gene mutation. To gain further understanding of MMR-competent familial colorectal cancer (FCC), we studied seven large families with an unexplained predisposition for CRC to identify genetic regions that could harbor CRC risk factors. First, we conducted a genome-wide linkage scan using 10K single-nucleotide polymorphism (SNP) arrays to search for disease loci. Second, we studied the genomic profiles of the tumors of affected family members to identify commonly altered genomic regions likely to harbor tumor suppressor genes. Finally, we studied the possible role of recently identified low-risk variants in the familial aggregation of CRC in these families. Linkage analysis did not reveal clear regions of linkage to CRC. However, our results provide support linkage to 3q, a region that has previously been linked to CRC susceptibility. Tumor profiling did not reveal any genomic regions commonly targeted in the tumors studied here. Overall, the genomic profiles of the tumors show some resemblance to sporadic CRC, but additional aberrations were also present. Furthermore, the FCC families did not appear to have an enrichment of low-risk CRC susceptibility loci. These data suggest that factors other than a highly penetrant risk factor, such as low or moderate-penetrance risk factors, may explain the increased cancer risk in a subset of familial CRCs.
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Affiliation(s)
- Anneke Middeldorp
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
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Sint Nicolaas J, Tjon ASW, Metselaar HJ, Kuipers EJ, de Man RA, van Leerdam ME. Colorectal cancer in post-liver transplant recipients. Dis Colon Rectum 2010; 53:817-21. [PMID: 20389217 DOI: 10.1007/dcr.0b013e3181cc90c7] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
PURPOSE Several malignancies have been reported to occur more often after liver transplantation. Whether this is also true for colorectal carcinoma is controversial. Our aims were 1) to compare the observed rate of colorectal carcinoma in a post-liver transplantation cohort with incidence data from the general Dutch population, and 2) to stratify for patients with and without primary sclerosing cholangitis, because primary sclerosing cholangitis is well established as a risk factor for colorectal carcinoma. METHODS We searched the medical records of liver transplantation patients who had a liver transplantation in our center between 1986 and 2007 with a follow-up of at least 3 months. Incidence data from the general population were retrieved from the Dutch Comprehensive Cancer Registry. Outcome measures were defined as standardized incidence ratio and incidence rate per 100,000 person-years. RESULTS Three hundred ninety-four patients (58% men; mean age at liver transplantation, 46.6 y) were included in the 1986 to 2007 period. Bowel investigation before liver transplantation had been performed in 73% of patients. Median follow-up was 5.1 years (range, 0.25-20 y). The mean age at the end of follow-up was 52 years (SD, 13 y). Colorectal carcinoma was diagnosed in four patients (1%) during follow-up. The overall standardized incidence ratio for colorectal carcinoma in post-liver transplant recipients was 2.16 (95% CI: 0.81-5.76) compared with the general population and 1.26 (95% CI: 0.31-5.03) for nonprimary sclerosing cholangitis post-liver transplant recipients. CONCLUSION This study suggests that the incidence of colorectal carcinoma is not increased in non-primary sclerosing cholangitis post-liver transplantation compared with the general population. A more intense colorectal carcinoma surveillance program based on this result remains controversial in nonprimary sclerosing cholangitis post-liver transplant recipients.
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Affiliation(s)
- Jerome Sint Nicolaas
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
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Adenoma-infiltrating lymphocytes (AILs) are a potential marker of hereditary nonpolyposis colorectal cancer. Am J Surg Pathol 2008; 32:1661-6. [PMID: 18753941 DOI: 10.1097/pas.0b013e31816ffa80] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Patients with hereditary nonpolyposis colorectal cancer syndrome (HNPCC) develop microsatellite-unstable colorectal cancers that tend to be more proximally located and are histologically more likely to show high numbers of tumor-infiltrating lymphocytes, a lack of dirty necrosis, mucinous or poor differentiation, and a Crohn-like host immune response, when compared with microsatellite-stable cancers. However, histologic features that are characteristic of and can perhaps distinguish colorectal adenomas in HNPCC patients from those occurring in the general population have not been previously reported. We compared 16 adenomas endoscopically removed from patients with genetically proven HNPCC to 32 control adenomas, group-matched for patient age and sex, along with endoscopic size, shape, anatomic location, and presence of high-grade dysplasia. Adenomas from HNPCC patients were more likely to contain high numbers of adenoma-infiltrating lymphocytes (AILs) with 12 of 16 (75%) adenomas having >or=5 AILs per high-power field (HPF) as opposed to 4 of 32 (12%) adenomas in the control group (P=0.00003). HNPCC adenomas were also less likely to contain increased numbers of apoptotic bodies: 7 of 16 (44%) contained >or=5 apoptoses per HPF, compared with 27 of 36 (84%) control adenomas (P=0.006). The presence of necrosis or serrated architecture, percent villous component, and numbers of mitotic figures per HPF did not differ significantly between the 2 groups. Therefore, increased numbers of AILs and decreased numbers of apoptoses in colorectal adenomas are simple and inexpensive markers that raise the possibility of HNPCC.
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Meurs-Szojda MM, Terhaar sive Droste JS, Kuik DJ, Mulder CJJ, Felt-Bersma RJF. Diverticulosis and diverticulitis form no risk for polyps and colorectal neoplasia in 4,241 colonoscopies. Int J Colorectal Dis 2008; 23:979-84. [PMID: 18594842 DOI: 10.1007/s00384-008-0510-4] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/29/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS There are conflicting data concerning the association between diverticular disease and colorectal carcinoma (CRC). This study was performed to determine the prevalence and association of diverticulosis, diverticulitis, polyps, and CRC. MATERIALS AND METHODS In a cross-sectional, retrospective study, we analyzed the colonoscopy reports of complete colonoscopies and patho-histological results of all patients referred for colonoscopy in a period of 3 months in 18 hospitals in The Netherlands. Diverticulosis was defined as three or more diverticula present and diverticulitis as diverticulosis with inflammation. Polyps were also coded according to localization and size. Advanced neoplastic lesions were defined as polyps >or=10 mm in diameter and/or villous architecture and/or adenomas with high grade dysplasia and/or invasive cancer. Actual and previous described CRC were registered. RESULTS A total of 4,241 patients were included in the study [1,996 (47%) male], mean age of 59 and range 18-95. Diverticula, diverticulitis, and polyps were seen in 1,052 (25%), 75 (2%), and 1,282 (30%) patients, respectively. No association was found between patients with polyps and those with and without diverticulosis (p=0.478). Invasive adenocarcinoma and adenomas >or=10 mm were most frequently observed. CRC was present in 372 (9%) patients. Negative relation between diverticulosis and CRC and invasive adenocarcinoma was observed. No association was found between polyps and CRC and patients with diverticulitis and CRC. In conclusion, there is no relation between patients with diverticulosis and higher incidence of polyps or CRC when using age-stratified analysis. No increased risk for polyps or CRC was found in patients with diverticulitis.
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Affiliation(s)
- M M Meurs-Szojda
- Department of Gastroenterology and Hepatology, VU University Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands
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Santos Jr JCM. Câncer ano-reto-cólico: aspectos atuais IV - câncer de cólon - fatores clínicos, epidemiológicos e preventivos. ACTA ACUST UNITED AC 2008. [DOI: 10.1590/s0101-98802008000300019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
O câncer colorretal tem alta incidência populacional e alto índice de mortalidade, com diferenças pouco relevantes entre os povos de diversas nações, como atestam os estudos epidemiológicos dessa doença. Embora a abordagem médico-cirúrgica do câncer colorretal tenha sido favorecida pelos novos conhecimentos adquiridos com a engenharia genética, pelos progressos que aprimoraram o tratamento, principalmente na área de neo-adjuvância, com as inovações nos aparelhos de radioterapia e com a constante introdução de novas e potentes substâncias quimioterápicas, o prognóstico da doença continua sombrio. Todavia, dados colhidos em estudos sobre a biologia do tumor - sua origem, crescimento e desenvolvimento e comportamento biológico - têm acenado para a possibilidade de cura quando os métodos preventivos, em prática, facilitam a abordagem precoce da lesão. Nesse contexto, o câncer colorretal é passível de cura, podendo, inclusive dispensar, para tanto, o tratamento adjuvante ou aliviar o paciente da abordagem cirúrgica mutilante. Assim, o maior esforço posto em ação no início desse século está sendo representado pelos movimentos de educação popular em massa para a prevenção do câncer de reto e dos cólons com incentivo para o teste de sangue oculto nas fezes.
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Szojda MM, Kuik DJ, Mulder CJJ, Felt-Bersma RJF. Colonic lavage with two polyethylene glycol solutions prior to colonoscopy makes no difference: a prospective randomized controlled trial. Scand J Gastroenterol 2008; 43:622-6. [PMID: 18415758 DOI: 10.1080/00365520701843001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE It is suggested that bowel preparations for colonoscopy are easier to tolerate when a smaller volume of solution with a more pleasant taste is used. The aim of this study was to establish equivalence between a 3-l sulphate-free polyethylene glycol solution (SF-PEG) and a 4-l PEG solution in effectiveness, patients' acceptability and tolerability. MATERIAL AND METHODS The study comprised 110 patients scheduled for elective colonoscopy and randomized to receive either SF-PEG or PEG. Before colonoscopy, the patients completed a questionnaire on stool frequency, medication, concomitant diseases, the amount of solution ingested, willingness to re-take it, volume of other fluid taken and tolerance of bowel preparation, taste of the laxative and occurrence of abdominal cramps. Three experienced endoscopists, blinded to the type of preparation, assigned bowel-cleansing scores using a validated 5-point scale to assess cleansing effect. RESULTS Data were available for 102 patients (44 M (40%), mean age 53 years, range 23-83 years). No significant differences were found in cleansing the rectosigmoid (p = 0.71) or complete colon (p = 0.79). Diverticulosis, constipation, gender and body mass index (BMI) did not influence cleansing. There was no significant difference in compliance between the two groups (p = 0.61). No differences were found for tolerance, taste and abdominal cramps. Patients who received SF-PEG had a preference for the same preparation next time in comparison with patients who had PEG cleansing (17 (33%) versus 4 (8%), respectively) (p = 0.03). CONCLUSIONS Both preparations are comparable in their cleansing effect and toleration. However, patients prefer cleansing with a smaller volume of solution. Improving the acceptability of colonic preparation could improve willingness to undergo colonoscopies in the future.
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Affiliation(s)
- Maria M Szojda
- Department of Gastroenterology and Hepatology, VU University Medical Centre, Amsterdam, The Netherlands
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Mecklin JP, Aarnio M, Läärä E, Kairaluoma MV, Pylvänäinen K, Peltomäki P, Aaltonen LA, Järvinen HJ. Development of colorectal tumors in colonoscopic surveillance in Lynch syndrome. Gastroenterology 2007; 133:1093-8. [PMID: 17919485 DOI: 10.1053/j.gastro.2007.08.019] [Citation(s) in RCA: 102] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2006] [Accepted: 07/12/2007] [Indexed: 12/02/2022]
Abstract
BACKGROUND & AIMS Mutation carriers in Lynch syndrome families have a high risk for developing colorectal cancer during their lifetime. This study was designed to assess the cumulative risk for the development of colorectal adenoma or carcinoma in prospective colonoscopic surveillance. METHODS Data from the Finnish Hereditary Colorectal Cancer Registry electronic database on 420 Lynch syndrome mutation carriers without previous colorectal tumors were reviewed. Between March 1982 and May 2005 the mutation carriers underwent a total of 1252 colonoscopies. The total follow-up time was 3150 years (mean, 6.7 y/patient). RESULTS The cumulative risk of adenoma by age 60 was estimated as 68% (95% confidence interval [CI], 50%-80%) in men and 48% (95% CI, 29%-62%) in women. The estimated cumulative risk up to age 60 years for the development of cancer found as a result of surveillance at an interval of 2-3 years was 35% (95% CI, 16%-49%) in men and 22% (95% CI, 7%-34%) in women. Half of the adenomas were located proximal to the splenic flexure. Extracolonic cancer was diagnosed in 73 patients (18%). CONCLUSIONS Adenoma would appear to be the most important lesion preceding cancer formation in Lynch syndrome and removal of adenomas decreases the risk for colorectal cancer (CRC). The Finnish surveillance protocol of colonoscopies at 2- to 3-year intervals facilitates patient adherence but includes an essential risk for CRC up to 60 years of age, but without CRC-related mortality when the surveillance instructions are followed.
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Shah M, Zhu K, Palmer RC, Jatoi I, Shriver C, Wu H. Breast, colorectal, and skin cancer screening practices and family history of cancer in U.S. women. J Womens Health (Larchmt) 2007; 16:526-34. [PMID: 17521256 DOI: 10.1089/jwh.2006.0108] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Several national medical organizations recommend more intensive screening or screening at an earlier age for individuals with a family history of breast, colorectal, or skin cancer. This study examined whether women with a family history of cancer were more likely to use breast, colorectal, or skin cancer screenings compared with those without such a family history. METHODS The data for this study came from female respondents who participated in the 2000 National Health Interview Survey. The age range of the study subjects and the definitions of cancer screening were determined based on the American Cancer Society recommendations on cancer screening. RESULTS When compared with women without a family history of breast cancer, women with a family history were more likely to undergo a screening mammogram. Women who had a family history of colorectal cancer were twice as likely to use colorectal cancer screening than women without a family history of colorectal cancer. The association of family history with colorectal and breast cancer screening was stronger among the younger age group for which a screening test is recommended if one has such a family history. The association between skin cancer screening and family history of skin cancer was significant only in younger women. CONCLUSIONS Women with a family history of cancer were more likely to have colorectal, breast, and skin cancer screening examinations. This may be a result of more physicians' recommendations and higher personal motivation for getting cancer screening, suggesting that the efficacy of national guidelines has been increasing somewhat.
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Affiliation(s)
- Mona Shah
- United States Military Cancer Institute, Walter Reed Army Medical Center, Washington, DC, USA.
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Koornstra JJ, Wesseling J, de Jong AE, Vasen HFA, Kleibeuker JH, Haagsma EB. Increased risk of colorectal neoplasia in asymptomatic liver-transplant recipients. Gut 2007; 56:892-3. [PMID: 17519499 PMCID: PMC1954848 DOI: 10.1136/gut.2007.120121] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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A procedure for the detection of linkage with high density SNP arrays in a large pedigree with colorectal cancer. BMC Cancer 2007; 7:6. [PMID: 17222328 PMCID: PMC1784097 DOI: 10.1186/1471-2407-7-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2006] [Accepted: 01/12/2007] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The apparent dominant model of colorectal cancer (CRC) inheritance in several large families, without mutations in known CRC susceptibility genes, suggests the presence of so far unidentified genes with strong or moderate effect on the development of CRC. Linkage analysis could lead to identification of susceptibility genes in such families. In comparison to classical linkage analysis with multi-allelic markers, single nucleotide polymorphism (SNP) arrays have increased information content and can be processed with higher throughput. Therefore, SNP arrays can be excellent tools for linkage analysis. However, the vast number of SNPs on the SNP arrays, combined with large informative pedigrees (e.g. >35-40 bits), presents us with a computational complexity that is challenging for existing statistical packages or even exceeds their capacity. We therefore setup a procedure for linkage analysis in large pedigrees and validated the method by genotyping using SNP arrays of a colorectal cancer family with a known MLH1 germ line mutation. METHODS Quality control of the genotype data was performed in Alohomora, Mega2 and SimWalk2, with removal of uninformative SNPs, Mendelian inconsistencies and Mendelian consistent errors, respectively. Linkage disequilibrium was measured by SNPLINK and Merlin. Parametric linkage analysis using two flanking markers was performed using MENDEL. For multipoint parametric linkage analysis and haplotype analysis, SimWalk2 was used. RESULTS On chromosome 3, in the MLH1-region, a LOD score of 1.9 was found by parametric linkage analysis using two flanking markers. On chromosome 11 a small region with LOD 1.1 was also detected. Upon linkage disequilibrium removal, multipoint linkage analysis yielded a LOD score of 2.1 in the MLH1 region, whereas the LOD score dropped to negative values in the region on chromosome 11. Subsequent haplotype analysis in the MLH1 region perfectly matched the mutation status of the family members. CONCLUSION We developed a workflow for linkage analysis in large families using high-density SNP arrays and validated this workflow in a family with colorectal cancer. Linkage disequilibrium has to be removed when using SNP arrays, because it can falsely inflate the LOD score. Haplotype analysis is adequate and can predict the carrier status of the family members.
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