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Magowan D, Abdulshafea M, Thompson D, Rajamoorthy SI, Owen R, Harris D, Prosser S. Blood-based biomarkers and novel technologies for the diagnosis of colorectal cancer and adenomas: a narrative review. Biomark Med 2024; 18:493-506. [PMID: 38900496 DOI: 10.1080/17520363.2024.2345583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Accepted: 03/12/2024] [Indexed: 06/21/2024] Open
Abstract
Aim: Blood-based biomarkers have shown promise for diagnosing colorectal cancer (CRC) and adenomas (CRA). This review summarizes recent studies in this area. Methods: A literature search was undertaken for 01/01/2017-01/03/2023. Criteria included CRC, CRA, liquid-biopsy, blood-based tests and diagnosis. Results: 12,378 studies were reduced to 178 for data extraction. Sixty focused on proteomics, 53 on RNA species, 30 on cfDNA methylation, seven on antigens and autoantibodies and 28 on novel techniques. 169 case control and nine cohort studies. Number of participants ranged 100-54,297, mean age 58.26. CRC sensitivity and specificity ranged 9.10-100% and 20.40-100%, respectively. CRA sensitivity and specificity ranged 8.00-95.70% and 4.00-97.00%, respectively. Conclusion: Sensitive and specific blood-based tests exist for CRC and CRA. However, studies demonstrate heterogenous techniques and reporting quality. Further work should concentrate on validation and meta-analyzes.
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Affiliation(s)
- Drew Magowan
- Swansea University, Singleton Park, SA2 8PP, Swansea, UK
- Swansea Bay University Health Board, Department of General Surgery, Morriston Hospital, SA6 6NL, Swansea, UK
| | - Mansour Abdulshafea
- Swansea Bay University Health Board, Department of General Surgery, Morriston Hospital, SA6 6NL, Swansea, UK
| | - Dominic Thompson
- Swansea Bay University Health Board, Department of General Surgery, Morriston Hospital, SA6 6NL, Swansea, UK
| | - Shri-Ishvarya Rajamoorthy
- Swansea Bay University Health Board, Department of General Surgery, Morriston Hospital, SA6 6NL, Swansea, UK
| | - Rhiannon Owen
- Swansea University, Singleton Park, SA2 8PP, Swansea, UK
| | - Dean Harris
- Swansea University, Singleton Park, SA2 8PP, Swansea, UK
- Swansea Bay University Health Board, Department of General Surgery, Morriston Hospital, SA6 6NL, Swansea, UK
| | - Susan Prosser
- Swansea Bay University Health Board, Department of General Surgery, Morriston Hospital, SA6 6NL, Swansea, UK
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Sullivan BA, Lieberman DA. Colon Polyp Surveillance: Separating the Wheat From the Chaff. Gastroenterology 2024; 166:743-757. [PMID: 38224860 DOI: 10.1053/j.gastro.2023.11.305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 11/20/2023] [Accepted: 11/22/2023] [Indexed: 01/17/2024]
Abstract
One goal of colorectal cancer (CRC) screening is to prevent CRC incidence by removing precancerous colonic polyps, which are detected in up to 50% of screening examinations. Yet, the lifetime risk of CRC is 3.9%-4.3%, so it is clear that most of these individuals with polyps would not develop CRC in their lifetime. It is, therefore, a challenge to determine which individuals with polyps will benefit from follow-up, and at what intervals. There is some evidence that individuals with advanced polyps, based on size and histology, benefit from intensive surveillance. However, a large proportion of individuals will have small polyps without advanced histologic features (ie, "nonadvanced"), where the benefits of surveillance are uncertain and controversial. Demand for surveillance will further increase as more polyps are detected due to increased screening uptake, recent United States recommendations to expand screening to younger individuals, and emergence of polyp detection technology. We review the current understanding and clinical implications of the natural history, biology, and outcomes associated with various categories of colon polyps based on size, histology, and number. Our aims are to highlight key knowledge gaps, specifically focusing on certain categories of polyps that may not be associated with future CRC risk, and to provide insights to inform research priorities and potential management strategies. Optimization of CRC prevention programs based on updated knowledge about the future risks associated with various colon polyps is essential to ensure cost-effective screening and surveillance, wise use of resources, and inform efforts to personalize recommendations.
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Affiliation(s)
- Brian A Sullivan
- Cooperative Studies Program Epidemiology Center-Durham, Durham VA Health Care System, Durham, North Carolina; Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
| | - David A Lieberman
- Portland Veteran Affairs Medical Center, Portland, Oregon; Division of Gastroenterology and Hepatology, School of Medicine, Oregon Health and Science University, Portland, Oregon
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Kildusiene I, Dulskas A, Smailyte G. Value of combined serum CEA, CA72-4, and CA19-9 marker detection in diagnosis of colorectal cancer. Tech Coloproctol 2024; 28:33. [PMID: 38358422 DOI: 10.1007/s10151-023-02873-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 10/18/2023] [Indexed: 02/16/2024]
Abstract
BACKGROUND The aim of this study was to examine whether the combination of serum tumor markers (carcinoembryonic antigen [CEA], carbohydrate antigen [CA]72-4, CA19-9) improves sensitivity and accuracy in the diagnosis of colorectal cancer and precancerous lesion tubular adenoma. METHODS An automatic electrochemiluminescence immunoassay with matched kits (ECLIA) was performed on a Roche Cobas e411 analyzer to determine the levels of serum CEA, CA72-4, and CA19-9 in 35 patients with early colorectal cancer, 87 patients with tubular adenoma, and 58 healthy people undergoing colonoscopy after positive fecal immunochemical test (FIT) in a colorectal cancer screening program 2021 January to April. The values of these three tumor markers in the diagnosis of colorectal cancer and tubular adenoma were analyzed. RESULTS 180 patients (92 female and 88 male) were included into the study. We compared serum CEA, CA72-4 and CA19-9 markers among 3 groups: healthy people (mean age 64,0 ±8,6), patients with tubular adenoma (mean age 62,7 ± 6,4) and colorectal cancer (mean age 59,2 ±6,2). The levels of serum CEA, CA72-4, and CA19-9 were higher in the colorectal cancer group than in the tubular adenoma group and healthy subjects, and these differences were significant (p < 0.05). The combination of CEA, CA72-4, and CA19-9 had a higher diagnostic value for colorectal cancer compared to single markers, and the positive detection rate was 54.3%. The diagnostic power when using all three markers was the best, and applied for colorectal cancer and tubular adenoma. CONCLUSIONS The combination of CA72-4, CEA, and CA19-9 markers increases the sensitivity and accuracy in the diagnosis of colorectal cancer and can thus be considered an important tool for early colorectal diagnosis.
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Affiliation(s)
- I Kildusiene
- Life Sciences Centre, Vilnius University, 03101, Vilnius, Lithuania.
- Laboratory of Cancer Epidemiology, National Cancer Institute, Vilnius, Lithuania.
| | - A Dulskas
- Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
- Department of Abdominal and General Surgery and Oncology, National Cancer Institute, Vilnius, Lithuania
| | - G Smailyte
- Laboratory of Cancer Epidemiology, National Cancer Institute, Vilnius, Lithuania
- Institute of Health Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
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Zhang J, Sun H, Xiong F, Lei S, Zhou G, Xiao X, Liu L, Wang P. The absolute number of small and diminutive adenomas with high-grade dysplasia is substantially higher compared with large adenomas: a retrospective pooled study. Front Oncol 2024; 14:1294745. [PMID: 38410098 PMCID: PMC10896556 DOI: 10.3389/fonc.2024.1294745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 01/22/2024] [Indexed: 02/28/2024] Open
Abstract
Introduction The risk that a large polyp (≥10 mm) evolves into high-grade dysplasia (HGD) is relatively high compared with that of a small/diminutive polyp (<10 mm). Recently, the detection of small and diminutive polyps has been substantially improved with the advancement of endoscopy. However, further research is needed on the role of the incidence of HGD caused by the co-occurrence of small and diminutive polyps in the progression of HGD. In this study, we aim to investigate whether and how the small and diminutive polyps correlate with the incidence of HGD in the population. Methods The pooled data were deeply analyzed from four published randomized controlled trials (RCTs) regarding colon polyp detection. All polyps detected were examined and confirmed by pathologists. The primary outcome was the composition ratio of the HGD polyps in each polyp size category. Results Among a total of 3,179 patients with 2,730 polyps identified, there were 83 HGD polyps confirmed, and 68 patients had at least one polyp with HGD. The risk of development of HGD was lower for a single small and diminutive polyp than for one large polyp (2.18% vs. 22.22%, P < 0.0001). On the contrary, the composition ratio for HGD from small and diminutive polyps was significantly higher than that from the large ones (68.67% vs. 31.33%, P < 0.0001). The combined number of HGD presented a trend negatively correlated to size. Conclusions Our data demonstrated that the absolute number of HGD significantly derives more from small and diminutive polyps than from the large ones, and the collective number of small and diminutive polyps per patient is indicative of his/her HGD exposure. These findings positively provide novel perspectives on the management of polyps and may further optimize the prevention of colorectal cancer. Systematic Review Registration http://www.chictr.org.cn, identifier ChiCTR1900025235, ChiCTR1800017675, ChiCTR1800018058, and ChiCTR1900023086.
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Affiliation(s)
- Jiancheng Zhang
- Department of Gastroenterology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Huajun Sun
- Department of Pathology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Fei Xiong
- Department of Gastroenterology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Shan Lei
- Department of Gastroenterology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Guanyu Zhou
- Department of Gastroenterology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Xun Xiao
- Department of Gastroenterology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Lin Liu
- Institute of Natural Sciences, MOE-LSC, School of Mathematical Sciences, CMA-Shanghai, and SJTU-Yale Joint Center for Biostatistics and Data Science, Shanghai Jiao Tong University, Shanghai, China and Shanghai Artificial Intelligence Laboratory, Shanghai, China
| | - Pu Wang
- Department of Gastroenterology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
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Xu J, Chi P, Qin K, Li B, Cheng Z, Yu Z, Jiang C, Yu Y. Association between lifestyle and dietary preference factors and conventional adenomas and serrated polyps. Front Nutr 2024; 10:1269629. [PMID: 38268677 PMCID: PMC10806101 DOI: 10.3389/fnut.2023.1269629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Accepted: 12/20/2023] [Indexed: 01/26/2024] Open
Abstract
Introduction Both conventional adenoma (AD) and serrated polyp (SP) were known precursor lesions of colorectal cancer (CRC). Modifiable lifestyle factors were significantly associated with CRC risk, but whether these factors were related to the risk of different precursors of CRC needed to be clarified. This study aimed to evaluate the risks of AD and SP caused by lifestyle factors and compare the risk differences between AD and SP. Methods The study population was from the CRC screening cohort in Hangzhou, China. A total of 458,457 eligible individuals volunteered to undergo initial screening including the fecal immunochemical test (FIT) and the CRC risk assessment. Finally, 13,993 participants who had undergone colonoscopy tests and had been diagnosed at designated hospitals were selected in this study. All participants were required to fill out a questionnaire during the initial screening for collecting their information. The generalized estimate equation (GEE) model was used to assess the association between lifestyle factors/dietary preferences and AD/SP. Results The body mass index (BMI) and smoking were positively associated with the risks of only SP (BMI: OR = 1.50, 95%CI: 1.23-1.84; smoking: OR = 1.29, 95%CI: 1.07-1.55), only AD (BMI: OR = 1.53, 95%CI: 1.28-1.82; OR = 1.24, 95%CI: 1.11-1.39), and synchronous SP and AD (BMI: OR = 1.97, 95%CI: 1.40-2.75; smoking: OR = 1.53, 95%CI: 1.27-1.85). In the case-group comparison, smoking was more strongly associated with the risk of synchronous SP and AD than only AD. Alcohol drinking was positively associated with the risk of AD (OR = 1.28, 95%CI: 1.14-1.44), but no statistically significant difference was observed in risks in the case-group comparison. Furthermore, whole-grain intake was associated with a decreased risk of only AD (OR = 0.78, 95%CI: 0.65-0.93). However, white meat intake was positively associated with risks of only SP when compared with AD cases (OR = 1.60, 95%CI: 1.15-2.23). Conclusion The current study identified common risk factors such as BMI and smoking as well as different risks of certain factors (e.g., alcohol drinking and whole-grain intake) for SP and AD. However, there were still some factors, especially diet-related factors, that have not been fully elucidated in their association with the two lesions. Further research is needed in future to confirm and develop prevention strategies for different lesions.
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Affiliation(s)
- Jue Xu
- HangZhou Center for Disease Control and Prevention, Hangzhou, China
| | - Peihan Chi
- Department of Epidemiology and Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China
| | - Kang Qin
- HangZhou Center for Disease Control and Prevention, Hangzhou, China
| | - Biao Li
- HangZhou Center for Disease Control and Prevention, Hangzhou, China
| | - Zhongxue Cheng
- HangZhou Center for Disease Control and Prevention, Hangzhou, China
| | - Zhecong Yu
- HangZhou Center for Disease Control and Prevention, Hangzhou, China
| | - Caixia Jiang
- HangZhou Center for Disease Control and Prevention, Hangzhou, China
| | - Yunxian Yu
- Department of Epidemiology and Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China
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Tiankanon K, Aniwan S. What are the priority quality indicators for colonoscopy in real-world clinical practice? Dig Endosc 2024; 36:30-39. [PMID: 37422906 DOI: 10.1111/den.14635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 07/06/2023] [Indexed: 07/11/2023]
Abstract
Colonoscopy is widely used as a colorectal cancer (CRC) screening tool. The effectiveness of a screening colonoscopy is associated with a decreased risk of CRC. However, colonoscopy is an operator-dependent procedure, and endoscopists' quality performance varies widely. This article reviewed the priority metrics and practices that contribute to high-quality screening colonoscopy in real-world clinical practice. With growing evidence, quality indicators have been subject to intense research and associated with reducing postcolonoscopy CRC incidence and mortality. Some quality metrics can reflect an endoscopy unit-based practice (i.e. quality of bowel preparation and withdrawal time). Other quality indicators primarily reflect individuals' skill and knowledge (i.e. cecal intubation rate, adenoma detection rate, and appropriately assigned follow-up colonoscopy interval). Measurement and improvement of priority quality indicators for colonoscopy should be made at both the endoscopist and unit levels. Substantial evidence supports the impact of high-quality colonoscopy in reducing the incidence of postcolonoscopy CRC.
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Affiliation(s)
- Kasenee Tiankanon
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Satimai Aniwan
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Aiba T, Hijiya N, Akagi T, Tsukamoto Y, Hirashita Y, Kinoshita K, Uchida T, Nakada C, Kurogi S, Ueda Y, Shiroshita H, Shiraishi N, Murakami K, Inomata M, Moriyama M. Overexpression of VSNL1 Enhances Cell Proliferation in Colorectal Carcinogenesis. Pathobiology 2023; 91:121-131. [PMID: 37797604 DOI: 10.1159/000533877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 08/28/2023] [Indexed: 10/07/2023] Open
Abstract
INTRODUCTION We have previously reported that overexpression of visinin-like protein 1 (VSNL1) is frequently observed in advanced colorectal adenocarcinomas and correlates with poorer prognosis. In this study, we determined the levels of VSNL1 expression in the earlier stages of colorectal tumors including adenomas and adenocarcinomas, and attempted to clarify the functional significance of VSNL1 overexpression in colorectal carcinogenesis. METHODS Levels of VSNL expression in colorectal tumor tissues were analyzed using immunohistochemistry. The effects of VSNL1 downregulation and overexpression on cell proliferation, resistance to apoptosis, and invasiveness were determined using two VSNL1-overexpressing colorectal cancer cell lines, CW-2 and HCT-116 and VSNL1 inducibly expressing SNU-C5, respectively. Gene expression signatures in VSNL1-downregulated CW-2 and HCT-116 were identified using transcriptome and gene set enrichment analyses. RESULTS VSNL1 expression was restricted to only a few crypt cells in the non-tumorous epithelium, whereas it became enhanced in adenomas and adenocarcinomas with the progression of tumorigenesis. Downregulation of VSNL1 in CW-2 and HCT-116 cells suppressed their proliferation through induction of apoptosis. Conversely, overexpression of VSNL1 in SNU-C5 cells enhanced resistance to anoikis. Transcriptome and gene set enrichment analyses revealed that downregulation of VSNL1 altered the expression level of the apoptosis-related gene set in CW-2 and HCT-116 cells. CONCLUSION VSNL1 plays a role in both the development and progression of colorectal tumors by enhancing cell viability.
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Affiliation(s)
- Takayuki Aiba
- Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan
- Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine, Oita University, Oita, Japan
| | - Naoki Hijiya
- Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan
| | - Tomonori Akagi
- Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine, Oita University, Oita, Japan
| | - Yoshiyuki Tsukamoto
- Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan
| | - Yuka Hirashita
- Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan
- Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan
| | - Keisuke Kinoshita
- Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan
- Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan
| | - Tomohisa Uchida
- Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan
- Department of Advanced Medical Sciences, Faculty of Medicine, Oita University, Oita, Japan
| | - Chisato Nakada
- Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan
- Department of Urology, Faculty of Medicine, Oita University, Oita, Japan
| | - Shusaku Kurogi
- Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan
| | - Yoshitake Ueda
- Department of Comprehensive Surgery for Community Medicine, Faculty of Medicine, Oita University, Oita, Japan
| | - Hidefumi Shiroshita
- Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine, Oita University, Oita, Japan
| | - Norio Shiraishi
- Department of Comprehensive Surgery for Community Medicine, Faculty of Medicine, Oita University, Oita, Japan
| | - Kazunari Murakami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan
| | - Masafumi Inomata
- Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine, Oita University, Oita, Japan
| | - Masatsugu Moriyama
- Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan
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Lanas Á, Balaguer F, Sánchez‐Luengo M, Hijos‐Mallada G, Hernández‐Mesa G, Piñero M, Castillo J, Ocaña T, Cubiella J, Crespo A, Iglesias Á, Medeiros I, Cacho G, Jover‐Martínez R, Alustiza M, Diaz‐Tasende J, Poves C, Macedo G, Quintero E. Fecal occult blood and calprotectin testing to prioritize primary care patients for colonoscopy referral: The advantage study. United European Gastroenterol J 2023; 11:692-699. [PMID: 37614054 PMCID: PMC10493338 DOI: 10.1002/ueg2.12446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 06/26/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND Colonoscopy is the gold standard for colorectal cancer (CRC) diagnosis and screening, but endoscopy services are usually overburdened. This study aims to investigate the usefulness of fecal hemoglobin (fHb) and calprotectin (FC) for the identification of patients with high probability of CRC who need urgent referral. METHODS In a multicenter prospective study, we enrolled symptomatic patients referred from primary care for colonoscopy. Prior to bowel preparation, fHb and FC quantitative tests were performed. The diagnostic performance was estimated for each biomarker/combination. We built a multivariable predictive model based on logistic regression, translated to a nomogram and a risk calculator to assist clinicians in the decision-making process. RESULTS The study included 1224 patients, of whom 69 (5.6%) had CRC. At the fHb cut-offs of >0 and 10 μg/g, the negative predictive values for CRC were 98.8% (95% confidence interval 97.8%-99.3%) and 98.6% (95%CI 97.7%-99.1%), and the sensitivities were 85.5% (95%CI 75.0%-92.8%) and 79.7% (95%CI 68.3%-88.4%), respectively. When we added the cut-off of 150 μg/g of FC to both fHb thresholds, the sensitivity of fecal tests improved. In the multivariate logistic regression model, the concentration of fHb was an independent predictor for CRC; age and gender were also independently associated with CRC. CONCLUSIONS fHb and FC are useful as part of a triage tool to identify those symptomatic patients with high probability of CRC. This can be easily applied by physicians to prioritize high-risk patients for urgent colonoscopy.
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Affiliation(s)
- Ángel Lanas
- University Clinic Hospital Lozano Blesa. University of Zaragoza. IIS Aragón. CIBERHEDZaragozaSpain
| | - Francesc Balaguer
- Department of GastroenterologyHospital Clínic de BarcelonaInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)University of BarcelonaBarcelonaSpain
| | - Marta Sánchez‐Luengo
- Department of GastroenterologyHospital Clínico Universitario Lozano BlesaZaragozaSpain
| | - Gonzalo Hijos‐Mallada
- Department of GastroenterologyHospital Clínico Universitario Lozano BlesaZaragozaSpain
| | - Goretti Hernández‐Mesa
- Department of GastroenterologyHospital Universitario de CanariasInstituto Universitario de Tecnologías Biomédicas (ITB) & Centro de Investigación Biomédica de Canarias (CIBICAN)Universidad de La LagunaTenerifeSpain
| | - Melisa Piñero
- Department of GastroenterologyHospital Universitario de CanariasInstituto Universitario de Tecnologías Biomédicas (ITB) & Centro de Investigación Biomédica de Canarias (CIBICAN)Universidad de La LagunaTenerifeSpain
| | - Joaquin Castillo
- Department of GastroenterologyHospital Clínic de BarcelonaInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)University of BarcelonaBarcelonaSpain
| | - Teresa Ocaña
- Department of GastroenterologyHospital Clínico Universitario Lozano BlesaZaragozaSpain
| | - Joaquín Cubiella
- Department of GastroenterologyComplexo Hospitalario Universitario de OurenseOurenseSpain
| | - Anais Crespo
- Department of GastroenterologyComplexo Hospitalario Universitario de OurenseOurenseSpain
| | - Águeda Iglesias
- Department of GastroenterologyComplexo Hospitalario Universitario de OurenseOurenseSpain
| | - Isabel Medeiros
- Department of GastroenterologyHospital Espirito Santo de ÉvoraÉvoraPortugal
| | - Guillermo Cacho
- Department of GastroenterologyHospital Universitario Fundación AlcorcónMadridSpain
| | | | - Miren Alustiza
- Department of GastroenterologyHospital General Universitario de AlicanteMadridSpain
| | - José Diaz‐Tasende
- Department of GastroenterologyHospital Universitario 12 de OctubreMadridSpain
| | - Carmen Poves
- Department of GastroenterologyHospital Clínico Universitario San CarlosMadridSpain
| | - Guilherme Macedo
- Department of GastroenterologyCentro Hospitalar São JoãoPortoPortugal
| | - Enrique Quintero
- Department of GastroenterologyHospital Universitario de CanariasInstituto Universitario de Tecnologías Biomédicas (ITB) & Centro de Investigación Biomédica de Canarias (CIBICAN)Universidad de La LagunaTenerifeSpain
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Berg EP, Mohammed A, Shipp ZJ, Tenegra JC. Colorectal Cancer Screening and Iron Deficiency Anemia. Prim Care 2023; 50:481-491. [PMID: 37516515 DOI: 10.1016/j.pop.2023.03.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/31/2023]
Abstract
In the United States, colorectal cancer has the fourth highest amount of annual new cancer cases per year between 2014 and 2018. In this article, the authors review the data and guidelines supporting effective direct visualization and stool-based testing methods of colon cancer screening along with work-up and management of Iron Deficiency Anemia.
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Affiliation(s)
- Ethan P Berg
- SIU Decatur Family Medicine Residency, 102 West Kenwood Avenue, Ste 100, Decatur, IL 62526, USA; Department of Family & Community Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA
| | - Asiya Mohammed
- Department of Family & Community Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA; SIU Springfield Family Medicine Residency, 520 N. 4th Street, Springfield, IL 62702, USA
| | - Zachary J Shipp
- SIU Decatur Family Medicine Residency, 102 West Kenwood Avenue, Ste 100, Decatur, IL 62526, USA; Department of Family & Community Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA
| | - Johnny C Tenegra
- SIU Decatur Family Medicine Residency, 102 West Kenwood Avenue, Ste 100, Decatur, IL 62526, USA; Department of Family & Community Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA; Department of Family & Community Medicine, Southern Illinois University School of Medicine Decatur Family Medicine Residency, Decatur, IL, USA.
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Heng D, Zhang M, Yuan Y, Qiu X. Alteration of Colonic Bacterial and Fungal Composition and Their Inter- and Intra-Kingdom Interaction in Patients with Adenomas with Low-Grade Dysplasia. Microorganisms 2023; 11:1327. [PMID: 37317301 DOI: 10.3390/microorganisms11051327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/08/2023] [Accepted: 05/15/2023] [Indexed: 06/16/2023] Open
Abstract
Colorectal cancer (CRC) develops from pre-cancerous cellular lesions in the gut epithelium and mainly originates from specific types of colonic adenomas with dysplasia. However, gut microbiota signatures among sampling sites in patients with colorectal adenomas with low-grade dysplasia (ALGD) and normal control (NC) remain uncharacterized. To characterize gut microbial and fungal profiles in ALGD and normal colorectal mucosa tissues. We used 16S and ITS1-2 rRNA gene sequencing and bioinformatics analysis on the microbiota of ALGD and normal colorectal mucosa from 40 subjects. Bacterial sequences in the ALGD group showed an increase in Rhodobacterales, Thermales, Thermaceae, Rhodobacteraceae, and several genera, including Thermus, Paracoccus, Sphingobium, and Pseudomonas, compared to the NC group. Fungal sequences in the ALGD group showed an increase in Helotiales, Leotiomycetes, and Basidiomycota, while several orders, families, and genera, including Verrucariales, Russulales, and Trichosporonales, were decreased. The study found various interactions between intestinal bacteria and fungi. The bacterial functional analysis showed increased glycogen and vanillin degradation pathways in the ALGD group. Meanwhile, the fungal functional analysis showed a decrease in pathways related to the biosynthesis of gondoate and stearate, as well as degradation of glucose, starch, glycogen, sucrose, L-tryptophan, and pantothenate, and an increase in the octane oxidation pathway in the ALGD group. The mucosal microbiota in ALGD exhibits altered fungal and microbial composition compared to the NC mucosa, potentially contributing to the development of intestinal cancer by regulating specific metabolic pathways. Therefore, these changes in microbiota and metabolic pathways may be potential markers for diagnosing and treating colorectal adenoma and carcinoma.
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Affiliation(s)
- Ding Heng
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing 210029, China
| | - Min Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing 210029, China
| | - Yuhan Yuan
- Department of Endoscopic Center, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing 210029, China
| | - Xinyun Qiu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing 210029, China
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
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11
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Schoenborn NL, Pollack CE, Gupta S, Boyd CM. Physician Decision-Making About Surveillance in Older Adults With Prior Adenomas: Results From a National Survey. Am J Gastroenterol 2023; 118:523-530. [PMID: 36662579 PMCID: PMC9992288 DOI: 10.14309/ajg.0000000000002193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 01/17/2023] [Indexed: 01/21/2023]
Abstract
INTRODUCTION There is no clear guidance on when surveillance colonoscopies should stop in older adults with prior adenomas. We aimed to examine physicians' decision-making regarding surveillance colonoscopies in older adults. METHODS In a national mailed survey of 1,800 primary care physicians (PCP) and 600 gastroenterologists, we asked whether physicians would recommend surveillance colonoscopy in vignettes where we varied patient age (75 and 85 years), health (good, medium, and poor), and prior adenoma risk (low and high). We examined the association between surveillance recommendations and patient and physician characteristics using logistic regression. We also assessed decisional uncertainty, need for decision support, and decision-making roles. RESULTS Of 1,040 respondents (response rate 54.8%), 874 were eligible and included. Recommendation for surveillance colonoscopies was lower if patient was older (adjusted proportions 20.6% vs 49.8% if younger), in poor health (adjusted proportions 7.1% vs 28.8% moderate health, 67.7% good health), and prior adenoma was of low risk (adjusted proportions 29.7% vs 41.6% if high risk). Family medicine physicians were most likely and gastroenterologists were least likely to recommend surveillance (adjusted proportions 40.0% vs 30.9%). Approximately 52.3% of PCP and 35.4% of gastroenterologists reported uncertainty regarding the benefit/harm balance of surveillance in older adults. Most (85.9% PCP and 77.0% gastroenterologists) would find a decision support tool helpful. Approximately 32.8% of PCP vs 71.5% of gastroenterologists perceived it as the gastroenterologist's role to decide about surveillance colonoscopies. DISCUSSION Studies to better evaluate the benefits/harms of surveillance colonoscopy in older adults and decisional support tools that help physicians and patients incorporate such data are needed.
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Affiliation(s)
- Nancy L Schoenborn
- Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Craig E Pollack
- Department of Health Policy and Management, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Samir Gupta
- Jennifer Moreno Veterans Affairs Medical Center, San Diego, California, USA
- Division of Gastroenterology and the Moores Cancer Center, University of California, San Diego, San Diego, California, USA
| | - Cynthia M Boyd
- Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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12
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Hu H, Gong X, Xu K, Luo S, Gao W, Li B, Jing D. Risk factor analysis of malignant adenomas detected during colonoscopy. Front Med (Lausanne) 2023; 10:1106272. [PMID: 36844218 PMCID: PMC9945521 DOI: 10.3389/fmed.2023.1106272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 01/13/2023] [Indexed: 02/10/2023] Open
Abstract
Background Several studies have shown that colorectal adenomas are the most important precancerous lesions. The colonoscopic identification of groups with the high risk of malignant colorectal adenomas remains a controversial issue for clinicians. Aims To evaluate the basic characteristics of colorectal adenomas with malignancy risk using high-grade dysplasia (HGD) as an alternative marker for malignant transformation. Methods Data from Shanghai General Hospital between January 2017 and December 2021 were retrospectively analyzed. The primary outcome was the incidence of HGD in adenomas, which was used as a surrogate marker for the risk of malignancy. Odds ratios (ORs) for the HGD rate in adenomas were analyzed in relation to adenoma-related factors. Results A total of 9,646 patients identified with polyps during 57,445 screening colonoscopies were included in the study. Patients with flat polyps, sessile polyps, and pedunculated polyps represented 27.3% (N = 2,638), 42.7% (N = 4,114), and 30.0% (N = 2,894) of the total number, respectively. HGD was found in 2.41% (N = 97), 0.92% (N = 24), and 3.51% (N = 98) of sessile adenomas, flat adenomas, and pedunculated adenomas, respectively (P < 0.001). Multivariable logistic regression showed that polyp size (P < 0.001) but not shape (P > 0.8), was an independent predictor of HGD. Contrast to the diameter ≤1 cm, the OR value for diameters 1-2, 2-3, and >3 cm was 13.9, 49.3, and 161.6, respectively. The HGD incidence also increased in multiple adenomas (>3 vs. >1, ORs 1.582) and distal adenomas (distal vs. proximal adenomas, OR 2.252). Adenoma morphology (pedunculated vs. flat) was statistically significant in univariate analysis but not when size was included in the multivariate analysis. Besides, the incidence of HGD was also significantly higher in older patients (>64 vs. <50 years old, OR = 2.129). Sex (P = 0.681) was not statistically significant. All these associations were statistically significant (P < 0.05). Conclusion The malignant potential of polyps is mostly affected by their size but not by their shape. In addition, distal location, multiple adenomas, and advanced age were also correlated with malignant transformation.
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Affiliation(s)
- Hong Hu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoyuan Gong
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kai Xu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shenzheng Luo
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Gao
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Baiwen Li
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Dadao Jing
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,*Correspondence: Dadao Jing,
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13
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Zhang Z, Ganguly E, Patel K, Dawsey S, Bledsoe J, Yang M. Sporadic hyperplastic polyp associated with above-average risk of developing metachronous colorectal cancer. Am J Cancer Res 2023; 13:669-677. [PMID: 36895974 PMCID: PMC9989619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Accepted: 01/08/2023] [Indexed: 03/11/2023] Open
Abstract
Post-colonoscopy surveillance interval for colorectal polyps depends on the size, number, and pathological classification of removed polyps. The risk of sporadic hyperplastic polyps (HPs) for developing colorectal adenocarcinoma remains debatable due to limited data. We aimed to evaluate the risk of metachronous colorectal cancer (CRC) in patients with sporadic HPs. A total of 249 patients with historical HP(s) diagnosed in 2003 were included as the disease group, and 393 patients without any polyp as the control group. All historical HPs were reclassified into SSA or true HP based on the recent 2010 and 2019 World Health Organization (WHO) criteria. Polyp size was measured under light microscope. Patients developed CRC were identified from the Tumor Registry database. Each tumor was tested for DNA mismatch repair proteins (MMR) by immunohistochemistry. Results showed that 21 (8%) and 48 (19%) historical HPs were reclassified as SSAs based on the 2010 and 2019 WHO criteria, respectively. The mean polyp size of SSAs (6.7 mm) was significantly larger than HPs (3.3 mm) (P<0.0001). For polyp size ≥5 mm, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for diagnosing SSA was 90%, 90%, 46%, and 99%, respectively. Left-sided polyps with size <5 mm were 100% of HPs. Five of 249 (2%) patients developed metachronous CRC during the 14-year follow-up from 2003 to 2017, including 2 of 21 (9.5%) patients with SSA diagnosed at intervals of 2.5 and 7 years, and 3 of 228 (1.3%) patients with HP(s) at 7, 10.3, and 11.9 years. Two of 5 cancers showed MMR deficiency with concurrent loss of MLH1/PMS2. Based on the 2019 WHO criteria, the rate of developing metachronous CRC in patients with SSA (P=0.0116) and HP (P=0.0384) was significantly higher than the control group, and no significant difference was observed between patients with SSA and with HP (P=0.241) in this cohort. Patients with either SSA or HP also had higher risk of CRC than average-risk US population (P=0.0002 and 0.0001, respectively). Our data add a new line of evidence that patients with sporadic HP are associated with above-average risk of developing metachronous CRC. Post-polypectomy surveillance for sporadic HP may be adjusted in future practice given the low but increased risk of developing CRC.
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Affiliation(s)
- Zhenwei Zhang
- Department of Pathology, University of Massachusetts Memorial Health Care Worcester 01605, MA, USA
| | - Eric Ganguly
- Gastroenterology, University of Vermont Medical Center Burlington 05401, VT, USA
| | - Krunal Patel
- Gastroenterology, University of Massachusetts Memorial Health Care Worcester 01605, MA, USA
| | - Sonja Dawsey
- Gastroenterology, University of Vermont Medical Center Burlington 05401, VT, USA
| | - Jacob Bledsoe
- Department of Pathology, Boston Children's Hospital Boston 02115, MA, USA
| | - Michelle Yang
- Department of Pathology, University of Massachusetts Memorial Health Care Worcester 01605, MA, USA.,Department of Pathology and Laboratory Medicine, University of Vermont Medical Center Burlington 05401, VT, USA
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14
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Chen C, Shi M, Liao Z, Chen W, Wu Y, Tian X. Oral sulfate solution benefits polyp and adenoma detection during colonoscopy: Meta-analysis of randomized controlled trials. Dig Endosc 2022; 34:1121-1133. [PMID: 35294782 PMCID: PMC9545996 DOI: 10.1111/den.14299] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 03/07/2022] [Accepted: 03/14/2022] [Indexed: 01/10/2023]
Abstract
OBJECTIVES Although oral sulfate solution (OSS) has been revealed to be not only safe and efficacious but also noninferior to polyethylene glycol with ascorbic acid (PEG + ASC), it is unclear whether OSS can ultimately increase the polyp detection rate (PDR) and adenoma detection rate (ADR). We performed this meta-analysis to estimate the effect of OSS on PDR and ADR during colonoscopy. METHODS We searched PubMed, EMBASE, and the Cochrane Library to identify relevant randomized controlled trials (RCTs) investigating the comparative effect of OSS versus PEG + ASC on the PDR and ADR during colonoscopy. Cecal intubation time (CIT), cecal intubation rate (CIR), and bowel preparation score were also evaluated. Review Manager (RevMan) version 5.3.0 was used to perform statistical analysis. RESULTS Eight RCTs involving 2059 patients fulfilled the selection criteria. Meta-analysis suggested that OSS significantly increased the PDR (47.34% vs. 40.14%, risk ratio [RR] 1.13, 95% confidence interval [CI] 1.03-1.24, P = 0.01) and ADR (44.60% vs. 38.14%, RR 1.17, 95% CI 1.03-1.33, P = 0.01) during colonoscopy. Subgroup analysis showed that the beneficial effects of OSS on PDR and ADR were consistent among patients with mean age >55 years and with body mass index <25 kg/m2 receiving outpatient colonoscopy, morning colonoscopy, and the 2-L bowel preparation protocol. Meanwhile, patients receiving OSS had a beneficial bowel preparation score. CONCLUSION Compared with polyethylene glycol-based regimens, the OSS bowel preparation regimen significantly increased the PDR and ADR in patients undergoing colonoscopy.
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Affiliation(s)
- Cheng Chen
- Department of Gastroenterology, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized TreatmentChongqing University Cancer HospitalChongqingChina
| | - Mengyang Shi
- Department of Gastroenterology, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized TreatmentChongqing University Cancer HospitalChongqingChina
| | - Zhongli Liao
- Department of Gastroenterology, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized TreatmentChongqing University Cancer HospitalChongqingChina
| | - Weiqing Chen
- Department of Gastroenterology, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized TreatmentChongqing University Cancer HospitalChongqingChina
| | - Yongzhong Wu
- Radiation Oncology CenterChongqing University Cancer HospitalChongqingChina
| | - Xu Tian
- Nursing DepartmentUniversitat Rovira I VirgiliTarragonaSpain
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15
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Meng S, Zheng Y, Wang W, Su R, Zhang Y, Zhang Y, Guo B, Han Z, Zhang W, Qin W, Jiang Z, Xu H, Bu Y, Zhong Y, He Y, Qiu H, Xu W, Chen H, Wu S, Zhang Y, Dong C, Hu Y, Xie L, Li X, Zhang C, Pan W, Wu S, Hu Y. A computer-aided diagnosis system using white-light endoscopy for the prediction of conventional adenoma with high grade dysplasia. Dig Liver Dis 2022; 54:1202-1208. [PMID: 35045951 DOI: 10.1016/j.dld.2021.12.016] [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: 10/19/2021] [Revised: 12/26/2021] [Accepted: 12/26/2021] [Indexed: 12/24/2022]
Abstract
OBJECTIVES We developed a computer-aided diagnosis system called ECRCCAD using standard white-light endoscopy (WLE) for predicting conventional adenomas with high-grade dysplasia (HGD) to optimise the patients' management decisions during colonoscopy. METHODS Pretraining model was used to fine-tune the model parameters by transfer learning. 2,397 images of HGD and 2,487 low-grade dysplasia (LGD) images were randomly assigned (8:1:1) to the training, optimising, and internal validation dataset. The prospective validation dataset is the frames accessed from colonoscope videoes. One independent rural hospital provided an external validation dataset. Histopathological diagnosis was used as the standard criterion. The capability of the ECRCCAD to distinguish HGD was assessed and compared with two expert endoscopists. RESULTS The accuracy, sensitivity and specificity for diagnosis of HGD in the internal validation set were 90.5%, 93.2%, 87.9%, respectively. While 88.2%, 85.4%, 89.8%, respectively, for the external validation set. For the prospective validation set, ECRCCAD achieved an AUC of 93.5% in diagnosing HGD. The performance of ECRCCAD in diagnosing HGD was better than that of the expert endoscopist in the external validation set (88.2% vs. 71.5%, P < 0.0001). CONCLUSION ECRCCAD had good diagnostic capability for HGD and enabled a more convenient and accurate diagnosis using WLE.
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Affiliation(s)
- Sijun Meng
- Center for Digestive Disease, the Seventh Affiliated Hospital of Sun Yat-sen University, No. 628, Zhenyuan Rd, Guangming (New) District, Shenzhen, Guangdong 518107, China
| | - Yueping Zheng
- The Third Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350004, China; Department of Gastroenterology, zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361004, China
| | - Wangyue Wang
- Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 of Shangtang Road, XiaCheng District, Hangzhou, Zhejiang 310014, China; Tongxiang First People's Hospital, Tongxiang City, Zhejiang 353000, China
| | - Ruizhang Su
- Department of Gastroenterology, the Second Affiliated Hospital of Xiamen Medical College, xiamen, China
| | - Yu Zhang
- Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 of Shangtang Road, XiaCheng District, Hangzhou, Zhejiang 310014, China
| | - Yi Zhang
- Pucheng County Hospital of Traditional Chinese Medicine, Pucheng, Fujian 353400, China
| | - Bingting Guo
- Jiying (XiaMen) Technology Co., LTD, Xiamen, Fujian 361004, China
| | - Zhaofang Han
- Xiamen Cingene Science and technology co., LTD, Xiamen, Fujian 361004, China; State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University, Xiamen 361102, China
| | - Wen Zhang
- Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
| | - Wenjuan Qin
- zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, xiamen, Fujian 361004, China
| | - Zhenghua Jiang
- Department of Clinical Pharmacy, First Hospital of Nanping, Fujian 314500, China
| | - Haineng Xu
- University of Pennsylvania Perelman School of Medicine, Philadelphia, United States
| | - Yemei Bu
- Jiying (XiaMen) Technology Co., LTD, Xiamen, Fujian 361004, China; The School of Pharmacy in Fujian Medical University, No.1 Qiuyang Road, Fujian 350122, China
| | - Yuhuan Zhong
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Shangjie University Town, Fuzhou, Fujian 350122, China
| | - Yulong He
- Center for Digestive Disease, the Seventh Affiliated Hospital of Sun Yat-sen University, No. 628, Zhenyuan Rd, Guangming (New) District, Shenzhen, Guangdong 518107, China
| | - Hesong Qiu
- Jiying (XiaMen) Technology Co., LTD, Xiamen, Fujian 361004, China
| | - Wen Xu
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Shangjie University Town, Fuzhou, Fujian 350122, China
| | - Hong Chen
- Center for Digestive Disease, the Seventh Affiliated Hospital of Sun Yat-sen University, No. 628, Zhenyuan Rd, Guangming (New) District, Shenzhen, Guangdong 518107, China
| | - Siqi Wu
- Xiamen Cingene Science and technology co., LTD, Xiamen, Fujian 361004, China; School of Life Sciences, Xiamen University, Xiamen, Fujian 36110, China
| | - Yongxiu Zhang
- Pucheng County Hospital of Traditional Chinese Medicine, Pucheng, Fujian 353400, China
| | - Chao Dong
- Pucheng County Hospital of Traditional Chinese Medicine, Pucheng, Fujian 353400, China
| | - Yongchao Hu
- Pucheng County Hospital of Traditional Chinese Medicine, Pucheng, Fujian 353400, China
| | - Lizhong Xie
- Pucheng County Hospital of Traditional Chinese Medicine, Pucheng, Fujian 353400, China
| | - Xugong Li
- Department of Financial Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, United States
| | - Changhua Zhang
- Center for Digestive Disease, the Seventh Affiliated Hospital of Sun Yat-sen University, No. 628, Zhenyuan Rd, Guangming (New) District, Shenzhen, Guangdong 518107, China.
| | - Wensheng Pan
- Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 of Shangtang Road, XiaCheng District, Hangzhou, Zhejiang 310014, China.
| | - Shuisheng Wu
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Shangjie University Town, Fuzhou, Fujian 350122, China.
| | - Yiqun Hu
- Department of Gastroenterology, zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361004, China.
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A Noninvasive Risk Stratification Tool Build Using an Artificial Intelligence Approach for Colorectal Polyps Based on Annual Checkup Data. Healthcare (Basel) 2022; 10:healthcare10010169. [PMID: 35052332 PMCID: PMC8776068 DOI: 10.3390/healthcare10010169] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 12/17/2021] [Accepted: 01/12/2022] [Indexed: 12/11/2022] Open
Abstract
Colorectal cancer is the leading cause of cancer-related deaths worldwide, and early detection has proven to be an effective method for reducing mortality. The machine learning method can be implemented to build a noninvasive stratifying tool that helps identify patients with potential colorectal precancerous lesions (polyps). This study aimed to develop a noninvasive risk-stratified tool for colorectal polyps in asymptomatic, healthy participants. A total of 20,129 consecutive asymptomatic patients who underwent a health checkup between January 2005 and August 2007 were recruited. Positive relationships between noninvasive risk factors, such as age, Helicobacter pylori infection, hypertension, gallbladder polyps/stone, and BMI and colorectal polyps were observed (p < 0.0001), regardless of sex, whereas significant findings were noted in men with tooth disease (p = 0.0053). A risk stratification tool was developed, for colorectal polyps, that considers annual checkup results from noninvasive examinations. For the noninvasive stratified tool, the area under the receiver operating characteristic curve (AUC) of obese females (males) aged <50 years was 91% (83%). In elderly patients (>50 years old), the AUCs of the stratifying tools were >85%. Our results indicate that the risk stratification tool can be built by using random forest and serve as an efficient noninvasive tool to identify patients requiring colonoscopy.
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17
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Knapp GC, Alatise O, Olopade B, Samson M, Olasehinde O, Wuraola F, Odujoko OO, Komolafe AO, Arije OO, Castle PE, Smith JJ, Weiser MR, Kingham TP. Feasibility and performance of the fecal immunochemical test (FIT) for average-risk colorectal cancer screening in Nigeria. PLoS One 2021; 16:e0243587. [PMID: 33434195 PMCID: PMC7802943 DOI: 10.1371/journal.pone.0243587] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 11/10/2020] [Indexed: 02/06/2023] Open
Abstract
Introduction There is a paucity of prospective data on the performance of the fecal immunochemical test (FIT) for colorectal cancer (CRC) screening in sub-Saharan Africa. The aim of this exploratory analysis was to evaluate the feasibility and performance of FIT in Nigeria. Methods This was a prospective, single-arm study. A convenience sample of asymptomatic, average-risk individuals between 40–75 years of age were enrolled at Obafemi Awolowo University Teaching Hospital. Study participants returned in 48 hours with a specimen for ova and parasite (O&P) and qualitative FIT (50ug/g) testing. Participants with a positive FIT had follow-up colonoscopy and those with intestinal parasites were provided treatment. Results Between May-June 2019, 379 individuals enrolled with a median age of 51 years (IQR 46–58). In total, 87.6% (n = 332) returned for FIT testing. FIT positivity was 20.5% (95% CI = 16.3%-25.2%). Sixty-one (89.7%) of participants with a positive FIT had a follow-up colonoscopy (n = 61), of whom 9.8% (95%CI:3.7–20.2%) had an adenoma and 4.9% (95%CI:1.0–13.7%) had advanced adenomas. Presence of intestinal parasites was inversely related to FIT positivity (6.5% with vs. 21.1% without parasites, p = 0.05). Eighty-two percent of participants found the FIT easy to use and 100% would recommend the test to eligible family or friends if available. Conclusions Asymptomatic, FIT-based CRC screening was feasible and well tolerated in this exploratory analysis. However, the high FIT positivity and low positive predictive value for advanced neoplasia raises concerns about its practicality and cost effectiveness in a low-resource setting such as Nigeria.
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Affiliation(s)
- Gregory C. Knapp
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
- * E-mail:
| | - Olusegun Alatise
- Department of Surgery, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Bolatito Olopade
- Department of Medical Microbiology and Parasitology, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Marguerite Samson
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
| | - Olalekan Olasehinde
- Department of Surgery, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Funmilola Wuraola
- Department of Surgery, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Oluwole O. Odujoko
- Department of Morbid Anatomy and Forensic Medicine, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Akinwunmi O. Komolafe
- Department of Morbid Anatomy and Forensic Medicine, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Olujide O. Arije
- Institute of Public Health, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Philip E. Castle
- Department of Epidemiology and Public Health, Albert Einstein College of Medicine, Bronx, New York, United States of America
| | - J. Joshua Smith
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
| | - Martin R. Weiser
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
| | - T. Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
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Chang JJ, Chien CH, Chen SW, Chen LW, Liu CJ, Yen CL. Long term outcomes of colon polyps with high grade dysplasia following endoscopic resection. BMC Gastroenterol 2020; 20:376. [PMID: 33172387 PMCID: PMC7656717 DOI: 10.1186/s12876-020-01499-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Accepted: 10/14/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The risk of recurrent colonic adenoma associated with high-grade dysplasia (HGD) colon polyps at baseline colonoscopy remains unclear. We conducted a clinical cohort study with patients who underwent polypectomy during screen colonoscopy to assess recurrent colonic adenoma risk factors. METHODS 11,565 patients at our facility underwent screen colonoscopy between September 1998 and August 2007. Data from patients with HGD colon polyps who had undergone follow-up colonoscopy were included for analysis. RESULTS Data from 211 patients was included. Rates of metachronous adenoma and advanced adenoma at follow-up were 58% and 20%, respectively. Mean follow-up period was 5.5 ± 1.8 (3-12) years. Univariate logistic regression analysis revealed that an adenoma count of ≥ 3 at baseline colonoscopy was strongly associated with overall recurrence, multiple recurrence, advanced recurrence, proximal recurrence, and distal adenoma recurrence with odds ratios of 4.32 (2.06-9.04 95% CI), 3.47 (1.67-7.22 95% CI), 2.55 (1.11-5.89 95% CI), 2.46 (1.16-5.22 95% CI), 2.89 (1.44-5.78 95% CI), respectively. Multivariate analysis revealed gender (male) [P = 0.010; OR 3.09(1.32-7.25 95% CI)] and adenoma count ≥ 3 [P = 0.002; OR 3.08(1.52-6.24 95% CI)] at index colonoscopy to be significantly associated with recurrence of advanced adenoma. CONCLUSION Recurrence of colonic adenoma at time of follow-up colonoscopy is common in patients who undergo polypectomy for HGD colon adenomas during baseline colonoscopy. Risk of further developing advanced adenomas is associated with gender and the number of colon adenomas present.
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Affiliation(s)
- Jia-Jang Chang
- Division of Hepatogastroenterology, Keelung Chang Gung Memorial Hospital, No. 222, Mai Chin Road, Keelung, 204, Taiwan.,Keelung Division, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Cheng-Hung Chien
- Division of Hepatogastroenterology, Keelung Chang Gung Memorial Hospital, No. 222, Mai Chin Road, Keelung, 204, Taiwan.,Keelung Division, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Shuo-Wei Chen
- Division of Hepatogastroenterology, Keelung Chang Gung Memorial Hospital, No. 222, Mai Chin Road, Keelung, 204, Taiwan.,Keelung Division, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Li-Wei Chen
- Division of Hepatogastroenterology, Keelung Chang Gung Memorial Hospital, No. 222, Mai Chin Road, Keelung, 204, Taiwan.,Keelung Division, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Ching-Jung Liu
- Division of Hepatogastroenterology, Keelung Chang Gung Memorial Hospital, No. 222, Mai Chin Road, Keelung, 204, Taiwan.,Keelung Division, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Cho-Li Yen
- Division of Hepatogastroenterology, Keelung Chang Gung Memorial Hospital, No. 222, Mai Chin Road, Keelung, 204, Taiwan. .,Keelung Division, Chang Gung Memorial Hospital, Keelung, Taiwan.
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Abstract
Colorectal cancer screening is essential to detect and remove premalignant lesions to prevent the development of colorectal cancer. Multiple screening modalities are available, including colonoscopy and stool-based testing. Colonoscopy remains the gold standard for detection and removal of premalignant colorectal lesions. Screening guidelines by the American Cancer Society now recommend initiating screening for all average-risk adults at 45 years old. Family history of colorectal cancer, other cancers, and advanced colon polyps are strong risk factors that must be considered in order to implement earlier testing. Epidemiologic studies continue to show disparities in colorectal cancer incidence and mortality and wide variability in screening rates.
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Affiliation(s)
- Eric M Montminy
- Division of Gastroenterology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA
| | - Albert Jang
- Department of Internal Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA
| | - Michael Conner
- Department of Internal Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA
| | - Jordan J Karlitz
- Southeast Louisiana Veterans Health Care System, Gastroenterology Section, 2400 Canal St, Medicine Service, Ste 3H, New Orleans, LA 70119, USA; Division of Gastroenterology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
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20
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Synbiotic VSL#3 and yacon-based product modulate the intestinal microbiota and prevent the development of pre-neoplastic lesions in a colorectal carcinogenesis model. Appl Microbiol Biotechnol 2020; 104:8837-8857. [DOI: 10.1007/s00253-020-10863-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 08/06/2020] [Accepted: 08/26/2020] [Indexed: 02/06/2023]
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Rasmussen L, Nielsen HJ, Christensen IJ. Early Detection and Recurrence of Colorectal Adenomas by Combination of Eight Cancer-Associated Biomarkers in Plasma. Clin Exp Gastroenterol 2020; 13:273-284. [PMID: 32884322 PMCID: PMC7434628 DOI: 10.2147/ceg.s251633] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 07/27/2020] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION Plasma levels of eight combined proteins have shown value as biomarkers for detection of colorectal cancer (CRC). However, their value in identifying colorectal adenoma needs further evaluation. The aim was to evaluate the eight proteins (AFP, CA19-9, CEA, CyFra21-1, Ferritin, Galectin-3, hs-CRP and TIMP-1) in detection of high-risk adenoma (HRA) and in prediction of recurrence of adenoma. Furthermore, the discrimination between HRA and low-risk adenoma (LRA) or CRC lesions was evaluated. METHODS The study included 4698 individuals undergoing diagnostic colonoscopy. Automated ELISA platforms were used in the determination of protein levels in samples collected just before colonoscopy. RESULTS Univariably, five proteins (AFP, CEA, CyFra21-1, hs-CRP and TIMP-1), respectively, significantly discriminated individuals with HRA from individuals with non-malignant findings. Multivariably, the combination of CEA and hs-CRP improved performance; AUC= 0.63 (sensitivity=0.19 at specificity=0.90). CyFra21-1, Ferritin and TIMP-1 demonstrated significant discrimination between individuals with HRA and LRA in univariable analyses, respectively. Performance was improved in multivariable analysis; AUC=0.61 (sensitivity=0.13 at specificity=0.90). Discrimination between individuals with colorectal adenomas and healthy individuals was significant for CA19-9, CEA, hs-CRP and TIMP-1, respectively, in univariable analyses. Multivariable analysis improved performance; AUC=0.63 (sensitivity=0.17 at specificity=0.90). All proteins except AFP demonstrated significant discrimination between individuals with HRA and CRC. Combination of CEA, CyFra21-1, Ferritin, hs-CRP and TIMP-1 in multivariable analysis improved discrimination; AUC=0.78 (sensitivity=0.34 at specificity=0.90). Association between plasma levels of any of the eight proteins and recurrence of colorectal adenomas after endoscopic removal could not be demonstrated. DISCUSSION The protein panel shows a promising potential in detection of colorectal adenomas in general, but specifically of HRA. However, improvements are needed for the panel to be valuable as a screening test. Finally, plasma levels of the eight proteins were not predictive of recurrence of colorectal adenomas.
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Affiliation(s)
- Louise Rasmussen
- Department of Surgical Gastroenterology 360, Hvidovre Hospital, University of Copenhagen, Hvidovre2650, Denmark
- Correspondence: Louise RasmussenDepartment of Surgical Gastroenterology 360, Hvidovre Hospital, University of Copenhagen, Hvidovre2650, Denmark Email
| | - Hans Jørgen Nielsen
- Department of Surgical Gastroenterology 360, Hvidovre Hospital, University of Copenhagen, Hvidovre2650, Denmark
| | - Ib Jarle Christensen
- Department of Surgical Gastroenterology 360, Hvidovre Hospital, University of Copenhagen, Hvidovre2650, Denmark
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No evidence for increased prevalence of colorectal carcinoma in 399 Dutch patients with Birt-Hogg-Dubé syndrome. Br J Cancer 2019; 122:590-594. [PMID: 31857718 PMCID: PMC7028712 DOI: 10.1038/s41416-019-0693-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 11/24/2019] [Accepted: 12/03/2019] [Indexed: 12/15/2022] Open
Abstract
Background Previously, it has been suggested that colorectal polyps and carcinomas might be associated with Birt-Hogg-Dubé syndrome. We aimed to compare the occurrence of colorectal neoplasms between Dutch patients with Birt-Hogg-Dubé syndrome and their relatives without Birt-Hogg-Dubé syndrome. Methods In all, 399 patients with a pathogenic FLCN mutation and 382 relatives without the familial FLCN mutation were included. Anonymous data on colon and rectum pathology was provided by PALGA: the Dutch Pathology Registry. Results No significant difference in the percentage of individuals with a history of colorectal carcinoma was found between the two groups (3.6% vs 2.6%, p = 0.54). There was also no significant difference between the age at diagnosis, diameter, differentiation and location of the colorectal carcinomas. Significantly more individuals with Birt-Hogg-Dubé syndrome underwent removal of colorectal polyps (12.2% vs 6.3%, p = 0.005). However, there was no significant difference between the number of polyps per person, the histology, grade of dysplasia and location of the polyps. Conclusion Our data do not provide evidence for an increased risk for colorectal carcinoma in Birt-Hogg-Dubé syndrome, arguing against the need for colorectal surveillance. The difference in polyps might be due to a bias caused by a higher number of colonoscopies in patients with Birt-Hogg-Dubé syndrome.
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The Efficacy of Split-Dose Bowel Preparations for Polyp Detection: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2019; 114:884-892. [PMID: 30865011 DOI: 10.14309/ajg.0000000000000155] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Split-dose bowel preparation leads to superior colon cleansing for colonoscopy. However, the magnitude of benefit in detecting colonic polyps is uncertain. We performed a systematic review to synthesize the data on whether using a split-dose bowel preparation regimen improves the detection of polyps when compared with other dosing methods or regimen products. METHODS We searched MEDLINE, EMBASE, and CENTRAL databases (from the inception to June 2017) for randomized controlled trials that assessed the following: split-dose vs day-before, split-dose vs same-day (as colonoscopy), or different types of split-dose regimens for patients undergoing colonoscopy. We excluded studies limited to inpatients, children, or individuals with inflammatory bowel disease. We compared the number of patients undergoing colonoscopy with recorded detection of polyps, adenomas, advanced adenomas, sessile serrated polyps (SSPs), right colonic adenomas, right colonic polyps, or right colonic SSPs. RESULTS Twenty-eight trials fulfilled the inclusion criteria (8,842 participants). Of the seven trials comparing split-dose vs day-before bowel preparation regimens, there was an increased detection rate of adenomas (risk ratio (RR) 1.26, 95% confidence intervals (CIs): 1.10-1.44; 4 trials; 1,258 participants), advanced adenomas (RR 1.53, 95% CI: 1.22-1.92; 3 trials; 1,155 participants), and SSPs (RR 2.48, 95% CI: 1.21-5.09; 2 trials; 1,045 participants). Pooled estimates from 8 trials (1,587 participants) evaluating split-dose vs same-day bowel preparations yielded no evidence of statistical difference. For various split-dose vs split-dose trials, 14 fulfilled the criteria (5,496 participants) and no superior split-regimen was identified. CONCLUSIONS Compared with day-before bowel preparation regimens, split-dose bowel preparations regimens increase the detection of adenomas, advanced adenomas, and have the greatest benefit in SSP detection.
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Rubio CA, Schmidt PT. Disparate cell proliferation and p53 overexpression in colonic crypts with normal epithelial lining found below the neoplastic canopy of conventional adenomas. JOURNAL OF PATHOLOGY CLINICAL RESEARCH 2019; 5:154-163. [PMID: 30821124 PMCID: PMC6648389 DOI: 10.1002/cjp2.128] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Revised: 02/18/2019] [Accepted: 02/25/2019] [Indexed: 12/20/2022]
Abstract
We previously found colonic crypts with normal epithelial lining but with corrupted shapes (NECS) beneath the adenomatous tissue of conventional adenomas (CoAs). Here we assessed the distribution of proliferating cells (PCs) and explored the possible occurrence of p53‐upregulated cells in the NECS in a cohort of CoAs. Sections from 70 CoAs and from 12 normal colon segments were immunostained with the proliferation marker Ki67. In 60 of the 70 CoAs, additional sections were immunostained for the tumor suppressor p53 protein. NECS with asymmetric, haphazardly distributed single PC or PC clusters were recorded in 80% of the CoAs, with a continuous PC domain in one or both slopes of the crypts in 17%, and with haphazardly distributed single PCs in the remaining 3% of the CoAs. In the 12 normal segments (controls), the colon crypts demonstrated normal shapes with symmetric PC domains limited to the lower third portion of the crypts. In 30% of the 60 CoAs immunostained with p53 the NECS revealed haphazardly distributed p53‐upregulated cells, singly or in clusters. In sum, the apparently normal epithelium of the NECS beneath the adenomatous tissue of CoAs revealed an unprecedented relocation of the normal PC domains. This unexpected event and the occurrence of p53‐upregulated cells strongly suggest that the crypts beneath the neoplastic tissue of CoAs harbor somatic mutations. The accretion of putative mutated NECS beneath the neoplastic canopy of CoA emerges as a previously unaddressed major event, an event that might play an important role in the histogenesis of CoA in the human colon.
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Affiliation(s)
- Carlos A Rubio
- Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden
| | - Peter T Schmidt
- Department of Medicine, Karolinska Institute and University Hospital, Centre for Digestive Diseases, Stockholm, Sweden
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25
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Rösch T, Altenhofen L, Kretschmann J, Hagen B, Brenner H, Pox C, Schmiegel W, Theilmeier A, Aschenbeck J, Tannapfel A, von Stillfried D, Zimmermann-Fraedrich K, Wegscheider K. Risk of Malignancy in Adenomas Detected During Screening Colonoscopy. Clin Gastroenterol Hepatol 2018; 16:1754-1761. [PMID: 29902640 DOI: 10.1016/j.cgh.2018.05.043] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 05/09/2018] [Accepted: 05/20/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS A higher incidence of proximal interval cancers after colonoscopy has been reported in several follow-up studies. One possible explanation for this might be that proximally located adenomas have greater malignant potential. The aim of the present study was to assess the risk of malignancy in proximal versus distal adenomas in patients included in a large screening colonoscopy database; adenoma shape and the patients' age and sex distribution were also analyzed. METHODS Data for 2007-2012 from the German National Screening Colonoscopy Registry, including 594,614 adenomas identified during 2,532,298 screening colonoscopies, were analyzed retrospectively. The main outcome measure was the rate of high-grade dysplasia (HGD) in adenomas, used as a surrogate marker for the risk of malignancy. Odds ratios (ORs) for the rate of HGD found in adenomas were analyzed in relation to patient- and adenoma-related factors using multivariate analysis. RESULTS HGD histology was noted in 20,873 adenomas (3.5%). Proximal adenoma locations were not associated with a higher HGD rate. The most significant risk factor for HGD was adenoma size (OR 10.36 ≥1 cm vs <1 cm), followed by patient age (OR 1.26 and 1.46 for age groups 65-74 and 75-84 vs 55-64 years) and sex (OR 1.15 male vs female). In comparison with flat adenomas as a reference lesion, sessile lesions had a similar HGD rate (OR 1.02) and pedunculated adenomas had a higher rate (OR 1.23). All associations were statistically significant (P ≤ .05). CONCLUSIONS In this large screening database, it was found that the rates of adenomas with HGD are similar in the proximal and distal colon. The presence of HGD as a risk marker alone does not explain higher rates of proximal interval colorectal cancer. We suggest that certain lesions (flat, serrated lesions) may be missed in the proximal colon and may acquire a more aggressive biology over time. A combination of endoscopy-related factors and biology may therefore account for higher rates of proximal versus distal interval colorectal cancer.
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Affiliation(s)
- Thomas Rösch
- Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
| | - Lutz Altenhofen
- Central Research Institute of Ambulatory Health Care, Berlin, Germany
| | - Jens Kretschmann
- Central Research Institute of Ambulatory Health Care, Berlin, Germany
| | - Bernd Hagen
- Central Research Institute of Ambulatory Health Care, Berlin, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research and Division of Preventive Oncology, German Cancer Research Center, Heidelberg, Germany; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany
| | - Christian Pox
- Department of Medicine, Ruhr University Bochum, Knappschaftskrankenhaus, Germany
| | - Wolff Schmiegel
- Department of Medicine, Ruhr University Bochum, Knappschaftskrankenhaus, Germany
| | | | | | | | | | | | - Karl Wegscheider
- Department of Medical Biometry and Epidemiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
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Plasminogen activator inhibitor-1 is associated with the metabolism and development of advanced colonic polyps. Transl Res 2018; 200:43-53. [PMID: 30670154 DOI: 10.1016/j.trsl.2018.05.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Revised: 04/30/2018] [Accepted: 05/30/2018] [Indexed: 12/31/2022]
Abstract
Implications of plasminogen activator inhibitor-1 (PAI-1) in colonic polyps remain elusive. A prospective study was conducted with 188 consecutive subjects who underwent colonoscopy at a tertiary referral center. Biochemical parameters, serum PAI-1 levels, PAI-1 single-nucleotide polymorphisms (rs-1799889), and colonic polyp profiles were analyzed at baseline and 24 and 48 weeks postpolypectomy. Of 188 patients (mean age: 56.8 years), 78.7% had adenomas; the median polyp number and size were 2 and 1.2cm, respectively. Multivariate analyses revealed the following baseline associations: PAI-1 levels (95% confidence interval [CI] for estimated β: 0.012-0.223) and polyp pathology (0.294-0.63) with polyp size; polyp size (0.085-0.498) and platelet count (0.013-0.027) with PAI-1 levels. At 24 weeks postpolypectomy, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and platelet count were independently associated with PAI-1 levels. Among patients with colonic adenomas, baseline PAI-1 levels (95% CI odds ratio: 1.06-1.686; cut-off value: >10.65 ng/mL, area under curve: 0.662, P = 0.032) and the PAI-1-rs-17998894G/4G genotype (0.036-0.912) were associated with high-grade dysplasia. Compared with baseline levels, repeated measures analysis of variance showed that PAI-1 levels increased, with concurrent increased HOMA-IR indexes, but decreased alanine transaminase levels and polyp size in follow-up colonoscopies at 24 weeks postpolypectomy. PAI-1 returned to baseline levels, and HOMA-IRs and triglyceride/high-density lipoprotein-cholesterol ratios decreased at 48 weeks postpolypectomy. Taken together, serum PAI-1 levels were positively associated with colonic polyp size and high-grade dysplasia, which was modulated by the PAI-1-rs-17998894G/4G genotype. The beneficial postpolypectomy inflammatory and metabolic alterations might be transiently counter regulated by elevated PAI-1 levels, with a link to HOMA-IR.
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Tariq H, Kamal MU, Patel H, Patel R, Ameen M, Elona S, Khalifa M, Azam S, Zhang A, Kumar K, Baiomi A, Shaikh D, Makker J. Predicting the presence of adenomatous polyps during colonoscopy with National Cancer Institute Colorectal Cancer Risk-Assessment Tool. World J Gastroenterol 2018; 24:3919-3926. [PMID: 30228785 PMCID: PMC6141329 DOI: 10.3748/wjg.v24.i34.3919] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Revised: 07/25/2018] [Accepted: 08/01/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the National Cancer Institute (NCI) Colorectal Cancer (CRC) Risk Assessment Tool as a predictor for the presence of adenomatous polyps (AP) found during screening or surveillance colonoscopy.
METHODS This is a retrospective single center observational study. We collected data of adenomatous polyps in each colonoscopy and then evaluated the lifetime CRC risk. We calculated the AP prevalence across risk score quintiles, odds ratios of the prevalence of AP across risk score quintiles, area under curves (AUCs) and Youden’s indexes to assess the optimal risk score cut off value for AP prevalence status.
RESULTS The prevalence of AP gradually increased throughout the five risk score quintiles: i.e., 27.63% in the first and 51.35% in the fifth quintile. The odd ratios of AP prevalence in the fifth quintile compared to the first and second quintile were 2.76 [confidence interval (CI): 1.71-4.47] and 2.09 (CI: 1.32-3.30). The AUC for all patients was 0.62 (CI: 0.58-0.66). Youden’s Index indicated the optimal risk score cutoff value discriminating AP prevalence status was 3.60.
CONCLUSION Patients with the higher NCI risk score have higher risk of AP and subsequent CRC; therefore, measures to increase the effectiveness of CRC detection in these patients include longer withdrawal time, early surveillance colonoscopy, and choosing flexible colonoscopy over other CRC screening modalities.
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Affiliation(s)
- Hassan Tariq
- Division of Gastroenterology, Department of Medicine, BronxCare Health system, Bronx, NY 10457, United States
| | - Muhammad Umar Kamal
- Department of Medicine, BronxCare Health system, Bronx, NY 10457, United States
| | - Harish Patel
- Division of Gastroenterology, Department of Medicine, BronxCare Health system, Bronx, NY 10457, United States
| | - Ravi Patel
- Department of Medicine, BronxCare Health system, Bronx, NY 10457, United States
| | - Muhammad Ameen
- Department of Medicine, BronxCare Health system, Bronx, NY 10457, United States
| | - Shehi Elona
- Department of Medicine, BronxCare Health system, Bronx, NY 10457, United States
| | - Maram Khalifa
- Department of Medicine, BronxCare Health system, Bronx, NY 10457, United States
| | - Sara Azam
- Department of Medicine, BronxCare Health system, Bronx, NY 10457, United States
| | - Aiyi Zhang
- Department of Medicine, BronxCare Health system, Bronx, NY 10457, United States
| | - Kishore Kumar
- Division of Gastroenterology, Department of Medicine, BronxCare Health system, Bronx, NY 10457, United States
| | - Ahmed Baiomi
- Department of Medicine, BronxCare Health system, Bronx, NY 10457, United States
| | - Danial Shaikh
- Department of Medicine, BronxCare Health system, Bronx, NY 10457, United States
| | - Jasbir Makker
- Division of Gastroenterology, Department of Medicine, BronxCare Health system, Bronx, NY 10457, United States
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Strzelczyk N, Kwiatek S, Latos W, Sieroń A, Stanek A. Does the Numerical Colour Value (NCV) correlate with preneoplastic and neoplastic colorectal lesions? Photodiagnosis Photodyn Ther 2018; 23:353-361. [PMID: 30055281 DOI: 10.1016/j.pdpdt.2018.07.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Revised: 07/18/2018] [Accepted: 07/20/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND White light endoscopy (WLE) is the gold standard for detection of colorectal cancer. Autofluorescence endoscopy (AFE) is among the novel methods expected to increase the sensitivity and specificity of endoscopic diagnosis. The main objective of the study was to determine the diagnostic efficacy of AFE for the detection of preneoplastic and neoplastic colorectal lesions and to identify high-grade neoplasia using Numerical Colour Value (NCV). METHODS This retrospective study included 188 patients with colorectal mucosal lesions diagnosed on WLE and assessed using AFE; they were included in the study if a complete patient record was available (description of visualized colorectal lesions, NCV and histopathology report). The NCV was compared with the histological result. RESULTS Histology revealed 38 hyperplastic colon polyps, 77 low-grade dysplastic lesions, 17 high-grade dysplastic lesions, 24 adenocarcinomas and 32 inflammatory lesions. The mean NCVs of high-grade dysplasia (HGD) and adenocarcinoma were 2.24 ± 0.22 and 2.73 ± 0.16, respectively, significantly higher than the NCV of hyperplastic colon polyps (0.95 ± 0.06), low-grade dysplasia (LGD) (1.27 ± 0.05) and inflammatory lesions (1.26 ± 0.17). The NCV cut-off value for HGD and adenocarcinoma was set at 1.7. The sensitivity, specificity, PPV (positive predictive value) and NPV (negative predictive value) were 95.2%, 87.9%, 97.5%, 84.8%, respectively. CONCLUSION Our study showed that AFE could provide useful diagnostic information regarding preneoplastic and neoplastic colorectal lesions. Additionally, the NCV significantly correlated with the histopathology results.
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Affiliation(s)
- Natalia Strzelczyk
- Specialist Hospital No 2, Department of Internal Diseases, Angiology and Physical Medicine, Center for Laser Diagnosis and Therapy, Batorego Street 15, 41-902 Bytom, Poland
| | - Sebastian Kwiatek
- Specialist Hospital No 2, Department of Internal Diseases, Angiology and Physical Medicine, Center for Laser Diagnosis and Therapy, Batorego Street 15, 41-902 Bytom, Poland
| | - Wojciech Latos
- Specialist Hospital No 2, Department of Internal Diseases, Angiology and Physical Medicine, Center for Laser Diagnosis and Therapy, Batorego Street 15, 41-902 Bytom, Poland
| | - Aleksander Sieroń
- School of Medicine with the Division of Dentistry in Zabrze, Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnosis and Therapy, Medical University of Silesia, Batorego Street 15, 41-902 Bytom, Poland
| | - Agata Stanek
- School of Medicine with the Division of Dentistry in Zabrze, Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnosis and Therapy, Medical University of Silesia, Batorego Street 15, 41-902 Bytom, Poland.
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Shifts of Faecal Microbiota During Sporadic Colorectal Carcinogenesis. Sci Rep 2018; 8:10329. [PMID: 29985435 PMCID: PMC6037773 DOI: 10.1038/s41598-018-28671-9] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Accepted: 06/27/2018] [Indexed: 12/18/2022] Open
Abstract
Gut microbiota has been implicated in the etiopathogenesis of colorectal cancer. The development of colorectal cancer is a multistep process by which healthy epithelium slowly develops into preneoplastic lesions, which in turn progress into malignant carcinomas over time. In particular, sporadic colorectal cancers can arise from adenomas (about 85% of cases) or serrated polyps through the "adenoma-carcinoma" or the "serrated polyp-carcinoma" sequences, respectively. In this study, we performed 16 S rRNA gene sequencing of bacterial DNA extracted from faecal samples to compare the microbiota of healthy subjects and patients with different preneoplastic and neoplastic lesions. We identified putative microbial biomarkers associated with stage-specific progression of colorectal cancer. In particular, bacteria belonging to the Firmicutes and Actinobacteria phyla, as well as members of the Lachnospiraceae family, proved to be specific of the faecal microbiota of patients with preneoplastic lesions, including adenomas and hyperplastic polyps. On the other hand, two families of the Proteobacteria phylum, Alcaligeneaceae and Enterobacteriaceae, with Sutterella and Escherichia/Shigella being the most representative genera, appeared to be associated with malignancy. These findings, once confirmed on larger cohorts of patients, can represent an important step towards the development of more effective diagnostic strategies.
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Maratt JK, Calderwood AH, Saini SD. When and How to Stop Surveillance Colonoscopy in Older Adults: Five Rules of Thumb for Practitioners. Am J Gastroenterol 2018; 113:5-7. [PMID: 29206812 PMCID: PMC5821058 DOI: 10.1038/ajg.2017.461] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
A 79-year-old obese man with obstructive sleep apnea, who ambulates with assistance comes to you to discuss post-polypectomy surveillance colonoscopy. His last colonoscopy was performed 5 years ago, during which two small adenomas were removed.
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Affiliation(s)
- Jennifer K. Maratt
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, Veterans Affairs Medical Center, Ann Arbor, Michigan, USA
| | - Audrey H. Calderwood
- Section of Gastroenterology, Department of Internal Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
| | - Sameer D. Saini
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, Veterans Affairs Medical Center, Ann Arbor, Michigan, USA
- Veterans Affairs Center for Clinical Management and Research, Ann Arbor, Michigan, USA
- Institute for Healthcare Policy and Innovation, Michigan Medicine, Ann Arbor, Michigan,USA
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