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Upadhyay KG, Desai DC, Ashavaid TF, Dherai AJ. Evaluating the role of kynurenine/tryptophan ratio as an indicator of disease activity in Indian patients with inflammatory bowel disease. A case-control study. Scand J Gastroenterol 2025; 60:454-462. [PMID: 40214291 DOI: 10.1080/00365521.2025.2491784] [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: 01/20/2025] [Revised: 02/23/2025] [Accepted: 04/06/2025] [Indexed: 04/30/2025]
Abstract
BACKGROUND Tryptophan (T), an essential amino acid, is primarily metabolized (∼90%) to kynurenine (K) by indoleamine 2,3-dioxygenase 1 (IDO1) mainly in intestinal cells. In inflammatory bowel disease (IBD), there is an increase in IDO1 activity which would increase Kynurenine levels and Kynurenine/Tryptophan (K/T) ratio. We hypothesize that alteration in K/T may be an indicator of disease severity in IBD. METHODS 55 healthy controls (HC), 55 Ulcerative colitis (UC) (35 active and 20 remission) and 30 Crohn's disease (CD) (20 active and 10 remission) were enrolled from November 2020 to March 2023. Plasma Kyn & Trp were simultaneously estimated using ultra-high-pressure liquid chromatography (UPLC). K/T ratio was correlated with disease activity and fecal calprotectin. In 25 patients follow-up samples were also collected with change in disease activity. RESULTS Median K/T ratio was significantly higher in patients with active disease as compared to those in remission and HC (p < .0001). A cut-off of ≤41 distinguished remission/healthy controls with a sensitivity of 92.73%, specificity of 76.36%, and an AUC of 0.9 (95% CI: 0.83-0.95, p < .001). The K/T ratio correlated with FC levels at a diagnostic cut-off of 250 µg/g. A significant reduction in K/T ratio with disease activity was noted in 80% of follow-up patients. CONCLUSION The K/T ratio with a cut-off of 41, correlated with the disease activity in 82% of patients, suggesting that the K/T ratio alters remarkably with disease activity in IBD patients. These findings can be further assessed for disease marker in a larger cohort of IBD patients.
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Affiliation(s)
- Khushboo G Upadhyay
- Research Department, P. D. Hinduja Hospital and Medical Research Centre, Mahim, India
| | - Devendra C Desai
- Department of Gastroenterology, P. D. Hinduja Hospital and Medical Research Centre, Mahim, India
| | - Tester F Ashavaid
- Research Department, P. D. Hinduja Hospital and Medical Research Centre, Mahim, India
- Department of Biochemistry, P. D. Hinduja Hospital and Medical Research Centre, Mahim, India
| | - Alpa J Dherai
- Research Department, P. D. Hinduja Hospital and Medical Research Centre, Mahim, India
- Department of Biochemistry, P. D. Hinduja Hospital and Medical Research Centre, Mahim, India
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Wang SY, Dong XT, Yuan Z, Jin LX, Gao WF, Han YK, Ni KM, Liu ZC, Wang JY, Wei XM, Su XM, Peng X, Zhang CZ. Factors associated with false fecal immunochemical test results in colorectal cancer screening. World J Gastrointest Oncol 2025; 17:101487. [PMID: 40235883 PMCID: PMC11995355 DOI: 10.4251/wjgo.v17.i4.101487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 12/10/2024] [Accepted: 01/22/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Certain subgroups are at an increased risk of false fecal immunochemical test (FIT) results; however, related studies are limited, and the available evidence is conflicting. AIM To evaluate factors associated with false-positive and false-negative FIT results. METHODS This retrospective study was based on the database of the Tianjin Colorectal Cancer Screening Program from 2012 to 2020. A total of 4129947 residents aged 40-74 years completed at least one FIT. Of these, 24890 asymptomatic participants who underwent colonoscopy examinations and completed lifestyle questionnaires were included in the analysis. Multivariable logistic regression was performed to identify the factors associated with false FIT results. RESULTS Among the overall screening population, 88687 (2.15%) participants tested positive for FIT. The sensitivity, specificity, positive predictive value, and negative predictive value of FIT for advanced neoplasms were 58.2%, 44.8%, 9.7%, and 91.3%, respectively. Older age, female sex, smoking, alcohol consumption, higher body mass index, and hemorrhoids were significantly associated with increased odds of false-positive and lower odds of false-negative FIT results. Moreover, features of high-grade dysplasia or villous for advanced adenoma and the presence of cancer were also associated with lower odds of false-negative results, while irregular exercise and diverticulum were associated with higher odds of false-positive results. CONCLUSION FIT results may be inaccurate in certain subgroups. Our results provide important evidence for further individualization of screening strategies.
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Affiliation(s)
- Shu-Yuan Wang
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Xue-Tao Dong
- Department of Gastroenterology, Tianjin Union Medical Center, Tianjin 300121, China
| | - Zhen Yuan
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Lei-Xin Jin
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Wei-Feng Gao
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - You-Kui Han
- Department of General Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Ke-Min Ni
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Zhao-Ce Liu
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Jun-Ying Wang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Xiao-Meng Wei
- Hospital Infection Management Division, Tianjin Union Medical Center, Tianjin 300121, China
| | - Xiao-Min Su
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Xi Peng
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Chun-Ze Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
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Senthakumaran T, Tannæs TM, Moen AEF, Brackmann SA, Jahanlu D, Rounge TB, Bemanian V, Tunsjø HS. Detection of colorectal-cancer-associated bacterial taxa in fecal samples using next-generation sequencing and 19 newly established qPCR assays. Mol Oncol 2025; 19:412-429. [PMID: 38970464 PMCID: PMC11793011 DOI: 10.1002/1878-0261.13700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 05/15/2024] [Accepted: 06/28/2024] [Indexed: 07/08/2024] Open
Abstract
We have previously identified increased levels of distinct bacterial taxa within mucosal biopsies from colorectal cancer (CRC) patients. Following prior research, the aim of this study was to investigate the detection of the same CRC-associated bacteria in fecal samples and to evaluate the suitability of fecal samples as a non-invasive material for the detection of CRC-associated bacteria. Next-generation sequencing (NGS) of the 16S ribosomal RNA (rRNA) V4 region was performed to evaluate the detection of the CRC-associated bacteria in the fecal microbiota of cancer patients, patients with adenomatous polyp and healthy controls. Furthermore, 19 novel species-specific quantitative PCR (qPCR) assays were established to detect the CRC-associated bacteria. Approximately, 75% of the bacterial taxa identified in biopsies were reflected in fecal samples. NGS failed to detect low-abundance CRC-associated taxa in fecal samples, whereas qPCR exhibited high sensitivity and specificity in identifying all targeted taxa. Comparison of fecal microbial composition between the different patient groups showed enrichment of Fusobacterium nucleatum, Parvimonas micra, and Gemella morbillorum in cancer patients. Our findings suggest that low-abundance mucosa-associated bacteria can be detected in fecal samples using sensitive qPCR assays.
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Affiliation(s)
| | - Tone M. Tannæs
- Section for Clinical Molecular Biology (EpiGen)Akershus University HospitalLørenskogNorway
- Department of Clinical Molecular Biology, Institute of Clinical MedicineUniversity of OsloNorway
| | - Aina E. F. Moen
- Section for Clinical Molecular Biology (EpiGen)Akershus University HospitalLørenskogNorway
- Department of Clinical Molecular Biology, Institute of Clinical MedicineUniversity of OsloNorway
- Department of Methods Development and AnalyticsNorwegian Institute of Public HealthOsloNorway
| | - Stephan A. Brackmann
- Department of Gastroenterology, Division of MedicineAkershus University HospitalLørenskogNorway
- Institute for Clinical MedicineUniversity of OsloNorway
| | - David Jahanlu
- Department of Life Sciences and HealthOslo Metropolitan UniversityNorway
| | - Trine B. Rounge
- Department of Pharmacy, Centre for BioinformaticsUniversity of OsloNorway
- Department of ResearchCancer Registry of NorwayOsloNorway
| | - Vahid Bemanian
- Department of PathologyAkershus University HospitalLørenskogNorway
| | - Hege S. Tunsjø
- Department of Life Sciences and HealthOslo Metropolitan UniversityNorway
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Junhai Z, Fei L, Jixiang Z, Huabing X, Cheng T, Weiguo D. Negative predictive value of fecal immunochemical testing in significant bowel disease screening: a systematic review and meta-analysis. Int J Surg 2025; 111:1182-1190. [PMID: 38920326 PMCID: PMC11745644 DOI: 10.1097/js9.0000000000001844] [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: 04/23/2024] [Accepted: 06/12/2024] [Indexed: 06/27/2024]
Abstract
OBJECTIVES General practitioners (GPs) must assess significant bowel disease (SBD) in patients with lower bowel symptoms during primary care. Studies have evaluated the efficacy of fecal immunochemical testing (FIT) for SBD screening. However, the effectiveness of FIT remains controversial. This study aimed to investigate the value of FIT in SBD screening. METHODS PubMed, the Cochrane Database, and EMBASE were systematically searched. Studies that estimated FIT values in screening for SBD among patients with lower bowel symptoms were included. Sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), diagnostic odds ratio (DOR), and negative predictive value (NPV) were calculated. Additionally, the pooled area under the summary receiver operating characteristic (SROC) curve was analyzed. RESULTS A total of 8615 patients with lower bowel symptoms who underwent FIT and colonoscopy to screen for SBD were enrolled and assessed in this meta-analysis; of these, 1226 patients were ultimately diagnosed with SBD. The pooled sensitivity, specificity, PLR, NLR, DOR, and NPV of FIT in SBD screening were 0.65 (95% CI: 0.50-0.78), 0.85 (95% CI: 0.72-0.92), 4.2 (95% CI: 2.60-6.90), 0.41 (95% CI: 0.29-0.58), 10 (95% CI: 6-17), and 0.90 (95% CI: 0.87-0.94), respectively. Besides, the pooled SROC was 0.82 (95% CI: 0.78-0.85). CONCLUSIONS This study indicates that the FIT provides a favorable NPV for SBD screening and could be a valuable technique for GPs to rule out SBD in primary care. At the same time, GPs need to remain vigilant and refer patients to gastroenterologists when necessary.
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Affiliation(s)
- Zhen Junhai
- Department of General Practice, Renmin Hospital of Wuhan University
| | - Liao Fei
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China
| | - Zhang Jixiang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China
| | - Xie Huabing
- Department of General Practice, Renmin Hospital of Wuhan University
| | - Tan Cheng
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China
| | - Dong Weiguo
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China
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Liu KS, George R, Shin C, Xiong JQ, Jamali T, Liu Y, Roy P, Singh S, Ma S, El-Serag HB, Tan MC. Interval Advanced Adenomas and Neoplasia in Patients with Negative Colonoscopy Following Positive Stool-Based Colorectal Cancer Screening Test. Dig Dis Sci 2025; 70:350-359. [PMID: 39581897 PMCID: PMC11854550 DOI: 10.1007/s10620-024-08748-4] [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: 08/27/2024] [Accepted: 11/07/2024] [Indexed: 11/26/2024]
Abstract
BACKGROUND/AIMS Fecal occult blood test (FOBT) and fecal immunohistochemical test (FIT) are used for colorectal cancer (CRC) screening. However, when no adenomas are found following a positive FOBT/FIT, the future risk of advanced adenomas or colorectal cancer (CRC) is unclear. We determined the incidence and determinants of advanced adenomas or CRC after a negative index colonoscopy following a positive FOBT/FIT. METHODS We identified patients in the Harris Health System (Houston, Texas) who underwent a colonoscopy following a positive FOBT/FIT from 01/2010 to 01/2013. We compared the incidence rates of advanced adenomas (≥ 1 cm, villous histopathology, or high-grade dysplasia) or CRC through 12/2023 for patients without polyps on index colonoscopy (negative colonoscopy) to patients with polyps (positive colonoscopy). We examined risk factors for incident adenomas using Cox regression models. RESULTS Of 2096 patients, 1293 (61.7%) had negative index colonoscopy and 803 (38.3%) had positive index colonoscopy. Overall, 411 patients (19.6%) underwent subsequent colonoscopy with incident adenomas in 241 patients and no incident CRC over mean 12.5 years. The incidence rate of advanced adenomas was 2.08 per 100 person-years after positive index colonoscopy compared to 0.65 per 100 person-years after negative index colonoscopy (age-adjusted incidence rate ratio 3.08, 95% CI 1.27-7.48). Non-Hispanic white race was the strongest risk factor for incident adenomas among patients with negative index colonoscopy. CONCLUSIONS We found a low likelihood of advanced adenomas and no interval CRC following negative index colonoscopy after positive FOBT/FIT. Non-Hispanic white race was a risk factor for incident adenomas, and these patients may warrant closer surveillance.
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Affiliation(s)
- Kyle S Liu
- Department of Internal Medicine, Washington University in St. Louis, St. Louis, MO, USA
| | - Rollin George
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM 285, Houston, TX, USA
| | - Caleb Shin
- Department of Orthopedic Surgery, HCA Medical City Denton, Denton, TX, USA
| | - Jia Q Xiong
- Department of Internal Medicine, Washington University in St. Louis, St. Louis, MO, USA
| | - Taher Jamali
- Divison of Gastroenterology, Henry Ford Hospital, Detroit, MI, USA
| | - Yan Liu
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM 285, Houston, TX, USA
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Priya Roy
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM 285, Houston, TX, USA
| | - Sonia Singh
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM 285, Houston, TX, USA
| | - Samuel Ma
- School of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM 285, Houston, TX, USA
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Mimi C Tan
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM 285, Houston, TX, USA.
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6
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Imagawa A, Takahashi S, Mabe K. Clinical Utility of Helicobacter pylori Stool Antigen Testing with a Bioluminescent Enzyme Immunoassay Using a Fecal Occult Blood Test Container. Intern Med 2024; 63:3271-3275. [PMID: 38719598 PMCID: PMC11729169 DOI: 10.2169/internalmedicine.3480-24] [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: 01/09/2024] [Accepted: 03/17/2024] [Indexed: 12/17/2024] Open
Abstract
Objective A dedicated stool container is required for Helicobacter pylori stool antigen testing. If H. pylori fecal antigen can be measured from a fecal occult blood test container (S fecal collection container or S container), which is widely used for colorectal cancer screening, screening of the upper and lower gastrointestinal tract can be performed with a single stool sample. We investigated the clinical usefulness of an H. pylori stool antigen assay using an S container. Materials A total of 347 patients who underwent esophagogastroduodenoscopy (EGD) were included. After the procedure, H. pylori stool antigen was measured using the S container and collection container recommended for H. pylori stool antigen (BL-stool collection container or BL container), and the qualitative outcomes of each were compared. A bioluminescent enzyme immunoassay (BLEIA) was used to measure H. pylori stool antigen. Results The overall agreement between S containers and BL containers was 100% (347/347), indicating that the qualitative outcomes were equivalent. As a secondary analysis, the results of the S container samples were evaluated according to the diagnosis made by physicians, and the overall agreement rate was 99.7% (345/346), indicating a high correlation. Conclusion The detection of H. pylori stool antigen using the S container is clinically useful because the results are equivalent to those obtained by the usual method. Screening of the upper and lower gastrointestinal tract is expected to be possible with a single stool sample in the future.
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Affiliation(s)
| | - Sho Takahashi
- Sapporo Shiroishi Internal Medicine and Gastroenterology Clinic, Japan
| | - Katsuhiro Mabe
- Junpukai Health Maintenance Center-Kurashiki, Japan
- Mabe Goryokaku Gastrointestinal Endoscopy Clinic, Japan
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Inoue Y, Ishiguro A, Suehiro Y, Kunimune Y, Yamaoka Y, Hashimoto S, Nakamura K, Goto A, Hamabe K, Matsumoto T, Tomochika S, Higaki S, Fujii I, Suzuki C, Koga M, Tsutsumi T, Lim LA, Matsubara Y, Yotsuyanagi H, Nagano H, Yamamoto N, Sakaida I, Takami T, Nishioka M, Yamasaki T. A novel index combining fecal immunochemical test, DNA test, and age improves detection of advanced colorectal adenoma. Cancer Sci 2024; 115:3682-3694. [PMID: 39180368 PMCID: PMC11531960 DOI: 10.1111/cas.16322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Revised: 07/30/2024] [Accepted: 08/08/2024] [Indexed: 08/26/2024] Open
Abstract
Although the fecal immunochemical test for hemoglobin (FIT) is a widely used screening test for colorectal cancer, it is not sensitive enough to detect advanced colorectal adenoma. To address this issue, we performed this study to investigate whether combining the FIT and fecal DNA testing of methylated somatostatin (SST) could improve diagnostic performance for advanced colorectal adenoma. We collected feces from 79 healthy subjects with negative results on colonoscopy, 43 patients with non-advanced colorectal adenoma, 117 patients with advanced colorectal adenoma, and 126 patients with colorectal cancer. After fecal DNA was incubated with methylation-sensitive restriction enzymes, SST methylation levels were measured by droplet digital PCR. Using logistic multivariate analysis, we established a prediction formula for detecting colorectal neoplasia and named it the FAMS (FIT, age, methylated SST) index. The diagnostic performance of a single use of FIT for advanced colorectal adenoma showed a sensitivity of 29.1% (34/117) and specificity of 89.3% (109/122). In contrast, the FAMS index showed a sensitivity of 56.4% (66/117) at a similar specificity point of 91.0% (111/122). Furthermore, even at the higher specificity point of 94.3% (115/122), the sensitivity was still higher than that of FIT, reaching 42.7% (50/117). As the FAMS index showed better diagnostic performance for advanced colorectal adenoma than a single use of FIT, the FAMS index could be a promising tool for detecting advanced colorectal adenoma.
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Affiliation(s)
- Yukari Inoue
- Faculty of MedicineYamaguchi University School of MedicineUbeJapan
| | - Akiyo Ishiguro
- Department of Oncology and Laboratory MedicineYamaguchi University Graduate School of MedicineUbeJapan
| | - Yutaka Suehiro
- Department of Oncology and Laboratory MedicineYamaguchi University Graduate School of MedicineUbeJapan
- Division of LaboratoryYamaguchi University HospitalUbeJapan
| | - Yuki Kunimune
- Department of Oncology and Laboratory MedicineYamaguchi University Graduate School of MedicineUbeJapan
- Division of LaboratoryYamaguchi University HospitalUbeJapan
| | - Yuko Yamaoka
- Department of Gastroenterology and HepatologyYamaguchi University Graduate School of MedicineUbeJapan
| | - Shinichi Hashimoto
- Department of Gastroenterology and HepatologyYamaguchi University Graduate School of MedicineUbeJapan
| | - Katsuhiko Nakamura
- Department of Gastroenterology and HepatologyYamaguchi University Graduate School of MedicineUbeJapan
| | - Atsushi Goto
- Department of Gastroenterology and HepatologyYamaguchi University Graduate School of MedicineUbeJapan
| | - Koichi Hamabe
- Department of Gastroenterology and HepatologyYamaguchi University Graduate School of MedicineUbeJapan
| | - Toshihiko Matsumoto
- Department of Gastroenterology and HepatologyYamaguchi University Graduate School of MedicineUbeJapan
| | - Shinobu Tomochika
- Department of Gastroenterological, Breast and Endocrine SurgeryYamaguchi University Graduate School of MedicineUbeJapan
| | - Shingo Higaki
- Department of GastroenterologySt. Hill HospitalUbeJapan
| | | | | | - Michiko Koga
- Division of Infectious Diseases, Advanced Clinical Research CenterThe Institute of Medical Science, The University of TokyoTokyoJapan
- Department of Infectious Diseases and Applied ImmunologyIMSUT Hospital of The Institute of Medical Science, The University of TokyoTokyoJapan
| | - Takeya Tsutsumi
- Division of Infectious Diseases, Advanced Clinical Research CenterThe Institute of Medical Science, The University of TokyoTokyoJapan
- Department of Infectious Diseases and Applied ImmunologyIMSUT Hospital of The Institute of Medical Science, The University of TokyoTokyoJapan
- Department of Infection Control and PreventionThe University of TokyoTokyoJapan
| | - Lay Ahyoung Lim
- Department of ResearchKitasato Institute Hospital, Kitasato UniversityTokyoJapan
| | - Yasuo Matsubara
- Department of Oncology and General MedicineIMSUT Hospital of The Institute of Medical Science, The University of TokyoTokyoJapan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research CenterThe Institute of Medical Science, The University of TokyoTokyoJapan
- Department of Infectious Diseases and Applied ImmunologyIMSUT Hospital of The Institute of Medical Science, The University of TokyoTokyoJapan
- Department of Oncology and General MedicineIMSUT Hospital of The Institute of Medical Science, The University of TokyoTokyoJapan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine SurgeryYamaguchi University Graduate School of MedicineUbeJapan
- Research Institute for Cell Design Medical ScienceYamaguchi UniversityUbeJapan
| | - Naoki Yamamoto
- Department of Gastroenterology and HepatologyYamaguchi University Graduate School of MedicineUbeJapan
- Health Science CenterYamaguchi UniversityYamaguchiJapan
| | - Isao Sakaida
- Department of Gastroenterology and HepatologyYamaguchi University Graduate School of MedicineUbeJapan
| | - Taro Takami
- Department of Gastroenterology and HepatologyYamaguchi University Graduate School of MedicineUbeJapan
- Research Institute for Cell Design Medical ScienceYamaguchi UniversityUbeJapan
| | | | - Takahiro Yamasaki
- Department of Oncology and Laboratory MedicineYamaguchi University Graduate School of MedicineUbeJapan
- Division of LaboratoryYamaguchi University HospitalUbeJapan
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8
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Chen M, Zhang J, Xu B, Yao B, Wang Z, Chen Y, Cai K, Zhang C. Performance of DNA methylation and blood-borne tumor indicators in detecting colorectal neoplasia and adenomas: a comparative study with the fecal occult blood test. Front Oncol 2024; 14:1373088. [PMID: 39544297 PMCID: PMC11560867 DOI: 10.3389/fonc.2024.1373088] [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: 01/19/2024] [Accepted: 10/11/2024] [Indexed: 11/17/2024] Open
Abstract
Objectives To evaluate the performance of stool methylated syndecan2 (mSDC2), methylated septin9 (mSEPT9), fecal occult blood test (FOBT), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) in detecting colorectal neoplasia and adenomas. Methods Blood-borne CEA, CA125, and CA199 levels were measured by electrochemiluminescence. The SDC2 methylation was detected by Methylation Detection Kit for Human SDC2 Gene (Real time PCR), and the SEPT9 methylation was detected by the Septin9 Gene Methylation Detection Kit based on PCR fluorescent probe assay. The colonoscopy combined with tissue biopsy pathology was used as a validation criterion for colorectal neoplasia. Results In detecting colorectal neoplasia, the AUCs of mSDC2, FOBT and mSEPT9 were 0.935 (95% CI: 0.915-0.956, P<0.001), 0.824 (95% CI: 0.617-1.000, P<0.001) and 0.671 (95% CI: 0.511-0.831, P<0.001), respectively. The sensitivity of mSDC2, FOBT and mSEPT9 were 100.0%, 66.7% and 40.0%, respectively. But the AUC of CEA, CA125 and CA199 were not statistically significant for colorectal neoplasia (all P>0.05). The combined application of mSEPT9 and mSDC2 showed the best predictive performance (AUC: 0.956, 95% CI: 0.887~1.000). For adenomas, the AUC of FOBT was extremely low (AUC: 0.524, 95% CI: 0.502-0.545, P=0.004). The CEA, CA125, CA199, mSEPT9 and mSDC2 were not statistically significant in detecting adenomas (all P>0.05). Conclusions For individual tests, FOBT and mSDC2 are relatively better indicators for detecting colorectal neoplasia compared to mSEPT9, CEA, CA125 and CA199. The combined form of mSEPT9 and mSDC2 to detect colorectal neoplasia has good predictive performance. However, none of these indicators demonstrated significant predictive power for detecting adenomas in our study.
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Affiliation(s)
| | | | | | | | | | | | | | - Chenli Zhang
- Department of General Practice, Ruijin Hospital, Shanghai Jiao Tong University School
of Medicine, Shanghai, China
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9
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Zhen J, Li J, Liao F, Zhang J, Liu C, Xie H, Tan C, Dong W. Development and validation of machine learning models for young-onset colorectal cancer risk stratification. NPJ Precis Oncol 2024; 8:239. [PMID: 39438621 PMCID: PMC11496529 DOI: 10.1038/s41698-024-00719-2] [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: 01/26/2024] [Accepted: 09/19/2024] [Indexed: 10/25/2024] Open
Abstract
Incidence of young-onset colorectal cancer (YOCRC, younger than 50) has significantly increased worldwide. The performance of fecal immunochemical test in detecting YOCRC is unsatisfactory. Using routine clinical data, we aimed to develop machine learning (ML) models to identify individuals with high-risk YOCRC who require further colonoscopy. We retrospectively extracted data of 10,874 young individuals. Multiple supervised ML techniques were devised to distinguish individuals with and without CRC, classifiers were trained, internally validated and temporally validated. In internal validation cohort, Random Forest (RF) ML model demonstrated good performance with AUC of 0.859 and highest recall of 0.840. In temporal validation cohort, the RF ML model also exhibited good classification performance, achieving AUC of 0.888 and highest recall of 0.872. RF algorithm-based approach is effective and feasible in YOCRC risk stratification. This could be valuable in assessing the risk of YOCRC so that clinical management, including further colonoscopy, can be subsequently made. (Registration: This study was registered with ClinicalTrials.gov (NCT06342622) on March 15, 2024.).
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Affiliation(s)
- Junhai Zhen
- Department of General Practice, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China
| | - Jiao Li
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China
| | - Fei Liao
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China
| | - Jixiang Zhang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China
| | - Chuan Liu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China
| | - Huabing Xie
- Department of General Practice, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China
| | - Cheng Tan
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China
| | - Weiguo Dong
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
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10
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Yamakawa T, Miyake T, Yokoyama Y, Kazama T, Hayashi Y, Hirayama D, Yoshii S, Yamano HO, Takahashi S, Nakase H. Clinical performance of fecal calprotectin, lactoferrin, and hemoglobin for evaluating the disease activity of IBD and detecting colorectal tumors. JGH Open 2024; 8:e13077. [PMID: 38835337 PMCID: PMC11148478 DOI: 10.1002/jgh3.13077] [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: 12/25/2023] [Revised: 03/20/2024] [Accepted: 04/18/2024] [Indexed: 06/06/2024]
Abstract
Background and Aim Recently, noninvasive fecal markers have been used as indicators of intestinal inflammation in patients with inflammatory bowel disease (IBD). We conducted a clinical validation study to measure fecal calprotectin (Cp), lactoferrin (Lf), and hemoglobin (Hb) levels using an all-in-one kit in patients with IBD and colorectal tumors and aimed to clarify the utility of these fecal markers. Methods In this study, 104 patients were analyzed, including 25 patients with ulcerative colitis (UC), 20 with Crohn's disease (CD), 48 with colorectal tumors, and 13 healthy controls (HC). Of the 48 patients with colorectal tumors, 14 had invasive cancer. We validated the utility of fecal Cp, Lf, and Hb levels by simultaneously measuring fecal markers in patients with IBD and colorectal tumors. Results Fecal Cp and Lf had almost equivalent abilities in detecting clinical remission in patients with UC; however, fecal Cp was slightly superior to Lf. Regarding colorectal tumors, fecal Cp and Lf levels tended to be higher in patients with adenomas and colorectal cancer than in HCs. Although fecal Hb alone had the best sensitivity and specificity for detecting colorectal cancer, it had relatively low sensitivity for detecting advanced neoplasms and colorectal cancer. Conclusion Fecal Cp and Lf can be used as almost equivalent biomarkers to assess the clinical activity in patients with UC. Fecal Hb is the most useful marker for screening colorectal cancer; however, adding fecal Cp and Lf may compensate for the low sensitivity of detecting for advanced colorectal tumors based on Hb alone.
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Affiliation(s)
- Tsukasa Yamakawa
- Department of Gastroenterology and Hepatology Sapporo Medical University School of Medicine Sapporo Japan
| | - Takakazu Miyake
- Department of Gastroenterology and Hepatology Sapporo Medical University School of Medicine Sapporo Japan
| | - Yoshihiro Yokoyama
- Department of Gastroenterology and Hepatology Sapporo Medical University School of Medicine Sapporo Japan
| | - Tomoe Kazama
- Department of Gastroenterology and Hepatology Sapporo Medical University School of Medicine Sapporo Japan
| | - Yuki Hayashi
- Department of Gastroenterology and Hepatology Sapporo Medical University School of Medicine Sapporo Japan
| | - Daisuke Hirayama
- Department of Gastroenterology and Hepatology Sapporo Medical University School of Medicine Sapporo Japan
| | - Shinji Yoshii
- Department of Gastroenterology and Hepatology Sapporo Medical University School of Medicine Sapporo Japan
| | - Hiro-O Yamano
- Department of Gastroenterology and Hepatology Sapporo Medical University School of Medicine Sapporo Japan
| | - Satoshi Takahashi
- Department of Infection Control and Laboratory Medicine Sapporo Medical University School of Medicine Sapporo Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology Sapporo Medical University School of Medicine Sapporo Japan
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11
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Clough J, Colwill M, Poullis A, Pollok R, Patel K, Honap S. Biomarkers in inflammatory bowel disease: a practical guide. Therap Adv Gastroenterol 2024; 17:17562848241251600. [PMID: 38737913 PMCID: PMC11085009 DOI: 10.1177/17562848241251600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 04/12/2024] [Indexed: 05/14/2024] Open
Abstract
Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), is a costly condition in terms of morbidity and healthcare utilization, with an increasing prevalence now approaching 1% in the Western world. Endoscopic assessment of IBD remains the gold standard for diagnosis, evaluation of treatment response and determination of post-operative recurrence, but is expensive and invasive. Biomarkers can facilitate non-invasive disease assessment, with C-reactive protein and faecal calprotectin as the most widely available biomarkers in current clinical practice. This narrative review summarizes the evidence for their use in both UC and CD and offers practical guidance for healthcare providers taking into account the limitations of biomarker interpretation. We present evidence for the future use of novel biomarkers in IBD and discuss how biomarker discovery could deliver the goal of precision medicine in IBD.
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Affiliation(s)
- Jennie Clough
- St George’s University Hospitals NHS Foundation Trust, London, UK
- School of Immunology and Microbial Sciences, King’s College London, London, UK
| | - Michael Colwill
- St George’s University Hospitals NHS Foundation Trust, London, UK
| | - Andrew Poullis
- St George’s University Hospitals NHS Foundation Trust, London, UK
| | - Richard Pollok
- St George’s University Hospital NHS Foundation Trust
- Institute of Infection and Immunity, St George’s University, London, UK
| | - Kamal Patel
- St George’s University Hospitals NHS Foundation Trust, London, UK
| | - Sailish Honap
- St George’s University Hospitals NHS Foundation Trust, London, UK
- School of Immunology and Microbial Sciences, King’s College London, London, UK
- INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France
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12
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Soares J, Eiras M, Ferreira D, Santos DAR, Relvas-Santos M, Santos B, Gonçalves M, Ferreira E, Vieira R, Afonso LP, Santos LL, Dinis-Ribeiro M, Lima L, Ferreira JA. Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer. Int J Mol Sci 2024; 25:3722. [PMID: 38612533 PMCID: PMC11012158 DOI: 10.3390/ijms25073722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 03/22/2024] [Accepted: 03/25/2024] [Indexed: 04/14/2024] Open
Abstract
Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen-a short-chain O-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection.
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Affiliation(s)
- Janine Soares
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal; (J.S.); (M.E.); (D.F.); (D.A.R.S.); (M.R.-S.); (B.S.); (M.G.); (E.F.); (L.P.A.); (L.L.S.)
- Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal
- REQUIMTE-LAQV, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Mariana Eiras
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal; (J.S.); (M.E.); (D.F.); (D.A.R.S.); (M.R.-S.); (B.S.); (M.G.); (E.F.); (L.P.A.); (L.L.S.)
| | - Dylan Ferreira
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal; (J.S.); (M.E.); (D.F.); (D.A.R.S.); (M.R.-S.); (B.S.); (M.G.); (E.F.); (L.P.A.); (L.L.S.)
- Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal
- Center for Applied Medical Research, University of Navarra, 31008 Pamplona, Spain
- i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
- INEB-Instituto Nacional de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal
| | - Daniela A. R. Santos
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal; (J.S.); (M.E.); (D.F.); (D.A.R.S.); (M.R.-S.); (B.S.); (M.G.); (E.F.); (L.P.A.); (L.L.S.)
- Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal
- Faculty of Medicine (FMUP), University of Porto, 4200-072 Porto, Portugal;
| | - Marta Relvas-Santos
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal; (J.S.); (M.E.); (D.F.); (D.A.R.S.); (M.R.-S.); (B.S.); (M.G.); (E.F.); (L.P.A.); (L.L.S.)
- Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal
- i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
- INEB-Instituto Nacional de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal
- REQUIMTE-LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal
| | - Beatriz Santos
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal; (J.S.); (M.E.); (D.F.); (D.A.R.S.); (M.R.-S.); (B.S.); (M.G.); (E.F.); (L.P.A.); (L.L.S.)
| | - Martina Gonçalves
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal; (J.S.); (M.E.); (D.F.); (D.A.R.S.); (M.R.-S.); (B.S.); (M.G.); (E.F.); (L.P.A.); (L.L.S.)
| | - Eduardo Ferreira
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal; (J.S.); (M.E.); (D.F.); (D.A.R.S.); (M.R.-S.); (B.S.); (M.G.); (E.F.); (L.P.A.); (L.L.S.)
| | - Renata Vieira
- Department of Pathology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal;
| | - Luís Pedro Afonso
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal; (J.S.); (M.E.); (D.F.); (D.A.R.S.); (M.R.-S.); (B.S.); (M.G.); (E.F.); (L.P.A.); (L.L.S.)
- Department of Pathology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal;
| | - Lúcio Lara Santos
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal; (J.S.); (M.E.); (D.F.); (D.A.R.S.); (M.R.-S.); (B.S.); (M.G.); (E.F.); (L.P.A.); (L.L.S.)
- Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal
- FF-I3ID, University Fernando Pessoa, 4249-004 Porto, Portugal
- GlycoMatters Biotech, 4500-162 Espinho, Portugal
- Department of Surgical Oncology, Portuguese Oncology Institute of Porto (IPO-Porto), 4200-072 Porto, Portugal
| | - Mário Dinis-Ribeiro
- Faculty of Medicine (FMUP), University of Porto, 4200-072 Porto, Portugal;
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI-IPOP), Rise@CI-IPOP (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal
- Department of Gastroenterology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal
| | - Luís Lima
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal; (J.S.); (M.E.); (D.F.); (D.A.R.S.); (M.R.-S.); (B.S.); (M.G.); (E.F.); (L.P.A.); (L.L.S.)
| | - José Alexandre Ferreira
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal; (J.S.); (M.E.); (D.F.); (D.A.R.S.); (M.R.-S.); (B.S.); (M.G.); (E.F.); (L.P.A.); (L.L.S.)
- Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal
- GlycoMatters Biotech, 4500-162 Espinho, Portugal
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Bae S, Lee K, Kim BC, Jun JK, Choi KS, Suh M. Cost-Utility Analysis for Colorectal Cancer Screening According to the Initiating Age of National Cancer Screening Program in Korea. J Korean Med Sci 2024; 39:e98. [PMID: 38501184 PMCID: PMC10948257 DOI: 10.3346/jkms.2024.39.e98] [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: 08/31/2023] [Accepted: 01/17/2024] [Indexed: 03/20/2024] Open
Abstract
BACKGROUND This study aimed to identify the most cost-effective strategy for colorectal cancer screening using the fecal immunochemical test (FIT), focusing on screening initiation age in Korea. METHODS We designed Markov simulation models targeting individuals aged 40 years or older. Twelve strategies combining screening initiation ages (40, 45, or 50 years old), termination ages (80 or no limit), and intervals (1 or 2 years) were modeled, and the most cost-effective strategy was selected. The robustness of the results was confirmed using one-way and probabilistic sensitivity analyses. Furthermore, the cost-effectiveness of the qualitative and quantitative FIT methods was verified using scenario analysis. RESULTS The 2-year interval strategy with a screening age range of 45-80 years was the most cost-effective (incremental cost-utility ratio = KRW 7,281,646/quality adjusted life years). The most sensitive variables in the results were transition rate from advanced adenoma to local cancer and discount rate. The uncertainty in the model was substantially low. Moreover, strategies starting at the age of 40 years were also cost-effective but considered suboptimal. The scenario analysis showed that there was no significant difference in cost-effectiveness between strategies with various relative screening ratio of quantitative and qualitative method. CONCLUSION The screening method for advancing the initiation age, as presented in the 2015 revised national screening recommendations, was superior regarding cost-effectiveness. This study provides a new paradigm for the development of a national cancer screening system in Korea, which can be utilized as a scientific basis for economic evaluations.
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Affiliation(s)
- Seowoo Bae
- National Cancer Control Institute, National Cancer Center, Goyang, Korea
- Department of Health Convergence, Ewha Womans University, Seoul, Korea
| | - Kyeongmin Lee
- Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
| | - Byung Chang Kim
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Jae Kwan Jun
- National Cancer Control Institute, National Cancer Center, Goyang, Korea
- Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
| | - Kui Son Choi
- National Cancer Control Institute, National Cancer Center, Goyang, Korea
- Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
| | - Mina Suh
- National Cancer Control Institute, National Cancer Center, Goyang, Korea
- Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
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14
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Cao X, Meng P, Liu Y, Li X, Shi X, Sun X, Zhang T, Wang J, Jiao H, Wang H, Zheng H. Adenoma location, size, and morphology are risk factors for FOBT false-negative results in inpatients with advanced colorectal adenoma. Sci Rep 2024; 14:831. [PMID: 38191805 PMCID: PMC10774257 DOI: 10.1038/s41598-024-51377-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 01/04/2024] [Indexed: 01/10/2024] Open
Abstract
Recently, advanced adenoma (AA) has been recognized as a target for colorectal cancer (CRC) screening. However, the fecal occult blood test (FOBT), the primary non-invasive screening method, shows limited sensitivity in detecting AA. This study investigates the relationship between adenoma characteristics and FOBT false-negative results. In a retrospective cohort study conducted from 2015 to 2022, we examined 342 inpatients with AA who underwent colonoscopy and received qualitative FOBT. FOBT sensitivity was analyzed about various adenoma characteristics, and logistic regression models were employed to investigate the relationship between adenoma features and FOBT false-negative outcomes. FOBT sensitivity in AA inpatients was 52.63%. Significant differences in sensitivity were observed based on adenoma location (left vs. right), morphology (with or without pedunculation), and size (≤ 10 mm vs. > 10 mm). After adjusting for several potential confounders, FOBT showed a reduced false-negative rate in AA with large-sized (OR, 0.49; 95% CI 0.31-0.77), left-sided location (OR, 0.53; 95% CI 0.31-0.89), and pedunculated morphology (OR, 0.73; 95% CI 0.43-1.24). AA with large size, left-sided location, and pedunculated morphology independently contribute to a decreased rate of FOBT false-negative results. However, these adenoma characteristics are not actively modifiable. Therefore, novel non-invasive methods are needed to improve AA detection accuracy.
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Affiliation(s)
- Xu Cao
- Department of Endoscopy, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, 050000, China
| | - Ping Meng
- Department of Gastroenterology, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, 050000, China
| | - Yong Liu
- Department of Endoscopy, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, 050000, China
| | - Xiaofang Li
- Department of Endoscopy, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, 050000, China
| | - Xiaoyang Shi
- Department of Endoscopy, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, 050000, China
| | - Xiaoxing Sun
- Department of Endoscopy, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, 050000, China
| | - Tianpeng Zhang
- Department of Anorectum, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, 050000, China
| | - Jinfeng Wang
- Department of Surgery, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, 050000, China
| | - Hao Jiao
- Department of Anorectum, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, 050000, China
| | - Huijie Wang
- Department of Endoscopy, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, 050000, China.
| | - Huanwei Zheng
- Department of Gastroenterology, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, 050000, China.
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15
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Li B, Liu S, Gao Y, Zheng L, Lu Y. Combined detection of SDC2/ADHFE1/PPP2R5C methylation in stool DNA for colorectal cancer screening. J Cancer Res Clin Oncol 2023; 149:10241-10253. [PMID: 37270460 DOI: 10.1007/s00432-023-04943-4] [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: 05/04/2023] [Accepted: 05/26/2023] [Indexed: 06/05/2023]
Abstract
BACKGROUND Colorectal cancer (CRC) is a disease of global concern, and its increasing incidence suggests the need for early and accurate diagnosis. The aim of this study was to investigate the value of combined detection of SDC2, ADHFE1 and PPP2R5C gene methylation in stool samples for early CRC screening. METHODS Stool samples from patients with CRC (n = 105), advanced adenoma (AA) (n = 54), non-advanced adenoma (NA) (n = 57), hyperplastic or other polyps (HOP) (n = 47) or no evidence of disease (NED) (n = 100) were collected from September 2021 to September 2022. The methylation levels of SDC2, ADHFE1 and PPP2R5C were quantified by quantitative methylation-specific polymerase chain reaction (qMSP), and faecal immunochemical testing (FIT) was performed. The diagnostic value was assessed using reporter operating characteristic (ROC) curve analysis. RESULTS The sensitivity of combined detection of SDC2/ADHFE1/PPP2R5C methylation in predicting CRC (0-IV) was 84.8%, the specificity was 98.0%, and the AUC was 0.930 (95% CI 0.889-0.970). Compared to FIT and serum tumour biomarkers, it showed better diagnostic performance for different stages of CRC. CONCLUSION The results of this study verified that the methylation levels of SDC2, ADHFE1 and PPP2R5C in stool DNA were significantly increased in CRC patients. Combined detection of SDC2/ADHFE1/PPP2R5C methylation is a potential non-invasive diagnostic method for CRC and precancerous lesion screening. CLINICAL TRIAL REGISTRATION Chinese Clinical Trials Registry, ChiCTR2100046662, registered on 26 May 2021, prospective registration.
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Affiliation(s)
- Ben Li
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shanglong Liu
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yuan Gao
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Longbo Zheng
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yun Lu
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
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Ribeiro U, Safatle-Ribeiro AV, Sorbello M, Kishi PHR, Cohend DD, Mattar R, Castilho VLP, Goncalves EMDN, Kawaguti F, Marques CFS, Alves VAF, Nahas SC, Eluf-Neto J. Implementation of an organized colorectal cancer screening program through quantitative fecal immunochemical test followed by colonoscopy in an urban low-income community: Guidance and strategies. Clinics (Sao Paulo) 2023; 78:100278. [PMID: 37639912 PMCID: PMC10474066 DOI: 10.1016/j.clinsp.2023.100278] [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: 04/19/2023] [Revised: 07/24/2023] [Accepted: 08/08/2023] [Indexed: 08/31/2023] Open
Abstract
Fecal Immunochemical Test (FIT) followed by a colonoscopy is an efficacious strategy to improve the adenoma detection rate and Colorectal Cancer (CRC). There is no organized national screening program for CRC in Brazil. The aim of this research was to describe the implementation of an organized screening program for CRC through FIT followed by colonoscopy, in an urban low-income community of São Paulo city. The endpoints of the study were: FIT participation rate, FIT positivity rate, colonoscopy compliance rate, Positive Predictive Values (PPV) for adenoma and CRC, and the rate of complications. From May 2016 to October 2019, asymptomatic individuals, 50-75 years old, received a free kit to perform the FIT. Positive FIT (≥ 50 ng/mL) individuals were referred to colonoscopy. 10,057 individuals returned the stool sample for analysis, of which (98.2%) 9,881 were valid. Women represented 64.8% of the participants. 55.3% of individuals did not complete elementary school. Positive FIT was 7.8% (776/9881). The colonoscopy compliance rate was 68.9% (535/776). There were no major colonoscopy complications. Adenoma were detected in 63.2% (332/525) of individuals. Advanced adenomatous lesions were found in 31.4% (165/525). CRC was diagnosed in 5.9% (31/525), characterized as adenocarcinoma: in situ in 3.2% (1/31), intramucosal in 29% (9/31), and invasive in 67.7% (21/31). Endoscopic treatment with curative intent for CRC was performed in 45.2% (14/31) of the cases. Therefore, in an urban low-income community, an organized CRC screening using FIT followed by colonoscopy ensued a high participation rate, and high predictive positive value for both, adenoma and CRC.
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Affiliation(s)
- Ulysses Ribeiro
- Departments of Gastroenterology, Universidade de São Paulo, São Paulo, SP, Brazil; Fundação Oncocentro de São Paulo (FOSP), São Paulo, SP, Brazil; Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (ICESP-HCFMUSP), São Paulo, SP, Brazil.
| | - Adriana Vaz Safatle-Ribeiro
- Departments of Gastroenterology, Universidade de São Paulo, São Paulo, SP, Brazil; Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (ICESP-HCFMUSP), São Paulo, SP, Brazil
| | - Maurício Sorbello
- Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (ICESP-HCFMUSP), São Paulo, SP, Brazil
| | | | - Diane Dede Cohend
- Preventive Medicine, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Rejane Mattar
- Departments of Gastroenterology, Universidade de São Paulo, São Paulo, SP, Brazil
| | | | | | - Fábio Kawaguti
- Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (ICESP-HCFMUSP), São Paulo, SP, Brazil
| | - Carlos Frederico Sparapan Marques
- Departments of Gastroenterology, Universidade de São Paulo, São Paulo, SP, Brazil; Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (ICESP-HCFMUSP), São Paulo, SP, Brazil
| | | | - Sérgio Carlos Nahas
- Departments of Gastroenterology, Universidade de São Paulo, São Paulo, SP, Brazil; Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (ICESP-HCFMUSP), São Paulo, SP, Brazil
| | - José Eluf-Neto
- Fundação Oncocentro de São Paulo (FOSP), São Paulo, SP, Brazil; Preventive Medicine, Universidade de São Paulo, São Paulo, SP, Brazil
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17
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Alhuzaim WM, Alloqmany GA, Almedemgh NI, Aldaham W, Alkhenaizan S, Hadal S. Positive Fecal Occult Blood Test and Colonoscopy With Histopathology Findings in Saudi Adults. Cureus 2023; 15:e43312. [PMID: 37700965 PMCID: PMC10492901 DOI: 10.7759/cureus.43312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2023] [Indexed: 09/14/2023] Open
Abstract
Background/aims Colorectal cancer cases are on the rise in developing countries, necessitating dependable detection tests. Moreover, medical procedures have become increasingly burdensome for both patients and healthcare professionals. This study aims to delve deeper into the fecal occult blood test (FOBT) as a potential solution. Settings and design The research took place at the Gastroenterology Specialized Clinic (Human Clinic) in Riyadh, Saudi Arabia. The study gathered results from colonoscopy/sigmoidoscopy, histopathology, and FOBT screening. Essential variables linked to colorectal cancer, including gastrointestinal symptoms, chronic diseases, hemoglobin (Hgb), body mass index (BMI), and medication usage, were documented to evaluate their potential predictive significance for positive outcomes. Methods and materials In line with the study aims, inclusion criteria covered Saudi adults aged 18 and above, experiencing lower GI symptoms, with colonoscopy or sigmoidoscopy, FOBT, and histopathological results. The resultant sample size was 72 patients. Non-Saudi individuals, symptoms-free patients, and those below 18 years were excluded. This retrospective analysis spanned from September 2021 to September 2022. For statistical analysis, after the data rationality was checked, parametric or non-parametric tests were used. P ≤ 0.05 was set as the significant level. Results Among the 72 patients, ranging in age from 18 to 80 (mean 42.94), males (57) outnumbered females (15). The average BMI was 27.56, with one-third of patients classified as overweight or obese. A majority of 47 (65.2%) exhibited normal Hgb levels while only five (7%) had abnormal levels. Results from colonoscopy or sigmoidoscopy and FOBT displayed statistical similarity between positive and negative outcomes. Additionally, the notable prevalence of positive results compared to negative ones underscores the resemblance between FOBT and colonoscopy/sigmoidoscopy findings. Conclusion Chronic illness, constitutional symptoms, BMI, and Hgb did not display a significant predictive value, However, the group with GI symptoms exhibited a strong prediction for favorable colonoscopy/sigmoidoscopy and histology outcomes. Additional research is necessary to validate these observed patterns.
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Affiliation(s)
- Waleed M Alhuzaim
- Department of Medicine, Imam Mohammed bin Saud Islamic University, Riyadh, SAU
| | - Ghaida A Alloqmany
- College of Medicine, Imam Mohammed Bin Saud Islamic University, Riyadh, SAU
| | - Norah I Almedemgh
- College of Medicine, Imam Mohammed Bin Saud Islamic University, Riyadh, SAU
| | - We'am Aldaham
- College of Medicine, Imam Mohammed Bin Saud Islamic University, Riyadh, SAU
| | | | - Shahad Hadal
- College of Medicine, Imam Mohammed bin Saud Islamic University, Riyadh, SAU
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18
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Santos DAR, Gaiteiro C, Santos M, Santos L, Dinis-Ribeiro M, Lima L. MicroRNA Biomarkers as Promising Tools for Early Colorectal Cancer Screening-A Comprehensive Review. Int J Mol Sci 2023; 24:11023. [PMID: 37446201 DOI: 10.3390/ijms241311023] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 06/30/2023] [Accepted: 06/30/2023] [Indexed: 07/15/2023] Open
Abstract
Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide. Early detection of this neoplasia has proven to improve prognosis, resulting in a 90% increase in survival. However, available CRC screening methods have limitations, requiring the development of new tools. MicroRNA biomarkers have emerged as a powerful screening tool, as they are highly expressed in CRC patients and easily detectable in several biological samples. While microRNAs are extensively studied in blood samples, recent interest has now arisen in other samples, such as stool samples, where they can be combined with existing screening methods. Among the microRNAs described in the literature, microRNA-21-5p and microRNA-92a-3p and their cluster have demonstrated high potential for early CRC screening. Furthermore, the combination of multiple microRNAs has shown improved performance in CRC detection compared to individual microRNAs. This review aims to assess the available data in the literature on microRNAs as promising biomarkers for early CRC screening, explore their advantages and disadvantages, and discuss the optimal study characteristics for analyzing these biomarkers.
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Affiliation(s)
- Daniela A R Santos
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal
- School of Health, Polytechnic Institute of Porto, Rua Dr. António Bernardino de Almeida, 400, 4200-072 Porto, Portugal
| | - Cristiana Gaiteiro
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal
| | - Marlene Santos
- School of Health, Polytechnic Institute of Porto, Rua Dr. António Bernardino de Almeida, 400, 4200-072 Porto, Portugal
- Centro de Investigação em Saúde e Ambiente (CISA), Escola Superior de Saúde, Instituto Politécnico do Porto, 4200-072 Porto, Portugal
- Molecular Oncology & Viral Pathology, IPO-Porto Research Center (CI-IPO), Portuguese Institute of Oncology, 4200-072 Porto, Portugal
| | - Lúcio Santos
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal
- Department of Surgical Oncology, Portuguese Institute of Oncology (IPO-Porto), 4200-072 Porto, Portugal
| | - Mário Dinis-Ribeiro
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI-IPOP), Rise@CI-IPOP (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal
- Department of Gastroenterology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal
| | - Luís Lima
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal
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19
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Lee E, Lee GH, Park B, Ahn SS, Noh CK. Positive faecal immunochemical test predicts the onset of inflammatory bowel disease: A nationwide, propensity score-matched study. Front Immunol 2023; 14:1128736. [PMID: 36860865 PMCID: PMC9968927 DOI: 10.3389/fimmu.2023.1128736] [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: 12/21/2022] [Accepted: 01/27/2023] [Indexed: 02/15/2023] Open
Abstract
Background & aims The faecal immunochemical test (FIT), a non-invasive test for screening colorectal cancer (CRC), is being increasingly understood to reflect heightened inflammation. We aimed to investigate the association between abnormal FIT results and onset of inflammatory bowel disease (IBD), a disease characterized with chronic gut mucosal inflammation. Methods Participants in the Korean National Cancer Screening Program for CRC between 2009-2013 were analysed and divided into positive and negative FIT result groups. The incidence rates of IBD after screening were calculated after excluding cases of haemorrhoids, CRC, and IBD at baseline. Cox proportional hazard analyses were used to identify independent risk factors for IBD occurrence during follow-up, and 1:2 propensity score matching was performed as a sensitivity analysis. Results In total, 229,594 and 815,361 participants were assigned to the positive and negative FIT result groups, respectively. The age- and sex-adjusted incidence rates of IBD in participants with positive and negative test results were 1.72 and 0.50 per 10,000 person-years, respectively. Adjusted Cox analysis revealed that FIT positivity was associated with a significantly higher risk of IBD (hazard ratio 2.93, 95% confidence interval: 2.46, 3.47, P <.001), which was consistent for both disease subtypes of ulcerative colitis and Crohn's disease. The results of Kaplan-Meier analysis in the matched population yielded identical findings. Conclusions Abnormal FIT results could be a preceding sign of incident IBD in the general population. Those with positive FIT results and suspected IBD symptoms could benefit from regular screening for early disease detection.
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Affiliation(s)
- Eunyoung Lee
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea,Office of Biostatistics, Ajou Research Institute for Innovative Medicine, Ajou University Medical Center, Suwon, Republic of Korea
| | - Gil Ho Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Bumhee Park
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea,Office of Biostatistics, Ajou Research Institute for Innovative Medicine, Ajou University Medical Center, Suwon, Republic of Korea
| | - Sung Soo Ahn
- Division of Rheumatology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea,*Correspondence: Sung Soo Ahn, ; Choong-Kyun Noh,
| | - Choong-Kyun Noh
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea,*Correspondence: Sung Soo Ahn, ; Choong-Kyun Noh,
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20
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Min L, Chen J, Yu M, Liu D. Using Circulating Tumor DNA as a Novel Biomarker to Screen and Diagnose Colorectal Cancer: A Meta-Analysis. J Clin Med 2023; 12:408. [PMID: 36675337 PMCID: PMC9860998 DOI: 10.3390/jcm12020408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/27/2022] [Accepted: 12/31/2022] [Indexed: 01/06/2023] Open
Abstract
(1) Background: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for many kinds of tumors. However, whether ctDNA could be an accurate diagnostic biomarker in colorectal cancer (CRC) remains to be clarified. The aim of this study was to evaluate the diagnostic accuracy of ctDNA in CRC. (2) Methods: PubMed, Web of Science, and Cochrane databases were searched to identify studies reporting the use of ctDNA to screen and diagnose CRC, and all relevant studies published until October 2022 were enrolled for our analysis. These studies were divided into three primer subgroups: the subgroup of quantitative or qualitative analysis of ctDNA and the subgroup of septin9 (SEPT9) methylation assay. (3) Results: A total of 79 qualified articles with 25,240 subjects were incorporated into our meta-analysis. For quantitative studies, the combined sensitivity (SEN), specificity (SPE), and diagnostic odds ratio (DOR) were 0.723 (95% CI: 0.623-0.803), 0.920 (95% CI: 0.827-0.966), and 23.305 (95% CI: 9.378-57.906), respectively, yielding an AUC of 0.860. The corresponding values for qualitative studies were 0.610 (95% CI: 0.566-0.651), 0.891 (95% CI: 0.878-0.909), 12.569 (95% CI: 9.969-15.848), and 0.823, respectively. Detection of SEPT9 methylation depicted an AUC of 0.879, with an SEN of 0.679 (95% CI: 0.622-0.732), an SPE of 0.903 (95% CI: 0.878-0.923), and a DOR of 20.121 (95% CI:14.404-28.106), respectively. (4) Conclusion: Blood-based ctDNA assay would be a potential novel biomarker for CRC screening and diagnosis. Specifically, quantitative analysis of ctDNA or qualitative analysis of SEPT9 methylation exhibited satisfying diagnostic efficiency. Larger sample studies are needed to further confirm our conclusions and to make the ctDNA approach more sensitive and specific.
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Affiliation(s)
- Liang Min
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha 410011, China
- Research Center of Digestive Disease, Central South University, Changsha 410011, China
| | - Jinghua Chen
- Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha 410013, China
| | - Meihong Yu
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha 410011, China
- Research Center of Digestive Disease, Central South University, Changsha 410011, China
| | - Deliang Liu
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha 410011, China
- Research Center of Digestive Disease, Central South University, Changsha 410011, China
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21
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Núñez Rodríguez MªH, Díez Redondo P, Riu Pons F, Cimavilla M, Loza A, Perez-Miranda M. Findings in the distal and proximal colon in colonoscopy screening after positive FIT and related pre-procedure factors. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS : ORGANO OFICIAL DE LA SOCIEDAD ESPANOLA DE PATOLOGIA DIGESTIVA 2022; 114:719-724. [PMID: 35285657 DOI: 10.17235/reed.2022.8409/2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Colonoscopy is the gold standard method for the early diagnosis and prevention of colorectal cancer (CRC). Screening programs include immune determination of blood in feces. Regardless of the method used, proximal colon lesions appear to be detected less frequently. OBJECTIVE Analyze the characteristics of proximal and distal lesions and possible predisposing factors. METHODS A cross-sectional study was performed of 692 patients from the CRC screening program with FIT ≥ 100ngHb/ml (October 2017 - October 2018). The right colon was examined twice as patients were participating in a randomized clinical trial to re-evaluate the right colon by forward-viewing endoscope or proximal retroflexion. The adenoma detection rate (ADR), advanced neoplasia (AN) and CRC in the proximal and distal colon, the histological and morphological characteristics in each section were analyzed. RESULTS 52.9% of the patients were male, with a mean age of 59.5 years (SD: 7.6). 1490 polyps were found and the ADR was 57.7% (distal 42% and proximal 37%). Detection rates were 45.8% for AN, 40.9% for advanced adenomas, 5.2% for advanced SSL and CRC was diagnosed in 4.8% of patients. Males had more AN than females. The mean age of patients with AN was significantly higher. AN were associated with smoking and alcohol consumption (p=0.0001). Globally, FIT levels were higher in patients with AN (p=0.003). Sixty-six per cent of cancers were distally located and 61.3% of CRC were diagnosed in the early stages. CONCLUSIONS In an average-risk asymptomatic population undergoing colonoscopy after positive FIT, AN were more common in the distal colon in males, older patients, smokers and those with alcohol intake.
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Affiliation(s)
| | | | | | | | - Andrea Loza
- Endoscopias/Digestivo, Hospital Santos Reyes
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22
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Performance of circulating methylated Septin9 gene DNA in diagnosis and recurrence monitoring of colorectal cancer in Western China. Clin Chim Acta 2022; 537:118-126. [DOI: 10.1016/j.cca.2022.10.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 09/22/2022] [Accepted: 10/21/2022] [Indexed: 12/24/2022]
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Yaghoobi M, Mehraban Far P, Mbuagbaw L, Yuan Y, Armstrong D, Thabane L, Moayyedi P. Potential Modifiers and Different Cut-offs in Diagnostic Accuracy of Fecal Immunochemical Test in Detecting Advanced Colon Neoplasia: A Diagnostic Test Accuracy Meta-analysis. Middle East J Dig Dis 2022; 14:382-395. [PMID: 37547494 PMCID: PMC10404105 DOI: 10.34172/mejdd.2022.299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 07/29/2022] [Indexed: 08/08/2023] Open
Abstract
Background: Fecal immunoglobulin test (FIT) has been advocated as the first line of screening for colorectal cancer (CRC) in several jurisdictions. Most studies have focused on CRC as the outcome of interest. Our goal was to quantify the diagnostic accuracy of different thresholds of FIT as compared with colonoscopy for detection of advanced colonic neoplasia and potential modifiers using proper Cochrane methodology. Methods: A comprehensive electronic search was performed for studies on FIT using colonoscopy as the reference standard to detect advanced neoplasia. Cochrane methodology was used to perform a diagnostic test accuracy (DTA) meta-analysis. Diagnostic accuracy of different cut-offs of FIT, including 25, 50, 75, 100, 150, and 200 ng/mL, were calculated separately. Meta-regression analysis was also performed to detect potential a priori modifiers, including age, location of the tumor, and time from FIT to colonoscopy. Results: Twenty-four studies were included with no evidence of publication bias. The sensitivity of FIT did not decrease with lowering the cut-off, although specificity increased in higher cut-offs. Commonly used cut-offs of 50 ng/mL, 75 ng/mL, and 100 ng/mL for FIT provided sensitivity of 39%, 36%, 27% and specificity of 92%, 94%, 96%, respectively. Diagnostic accuracy of FIT did not significantly differ in proximal versus distal lesions or in individuals below or over the age of 50 years. The results remained robust in a meta-regression of the location of the study, time from FIT to colonoscopy, and methodological quality. Conclusion: The sensitivity of FIT might have been overestimated in previous studies focusing on CRC, and it seems to be independent of age, location of neoplasia, or cut-offs, contrary to some previous studies. Lowering the cut-off will reduce the diagnostic odds ratio (DOR) by increasing specificity but without any effect on sensitivity.
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Affiliation(s)
- Mohammad Yaghoobi
- Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada
- Cochrane GUT, Hamilton, Ontario, Canada
- The Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada
| | - Parsa Mehraban Far
- Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
- Division of Medicine, Queen’s University, Kingston, Ontario, Canada
| | - Lawrence Mbuagbaw
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada
- Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada
- Biostatistics Unit/The Research Institute, St Joseph’s Healthcare, Hamilton, Ontario, Canada
| | - Yuhong Yuan
- Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
- Cochrane GUT, Hamilton, Ontario, Canada
- The Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada
| | - David Armstrong
- Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
- The Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada
| | - Lehana Thabane
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada
- Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada
- Biostatistics Unit/The Research Institute, St Joseph’s Healthcare, Hamilton, Ontario, Canada
- Departments of Anesthesia/Pediatrics; Schools of Nursing/Rehabilitation Sciences, Master University, Hamilton, Ontario, Canada
| | - Paul Moayyedi
- Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada
- Cochrane GUT, Hamilton, Ontario, Canada
- The Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada
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24
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Tran CTD, Nguyen MVT, Tran MT, Tuong TTV, Tran QH, Le LC, Pham HTT, Bui NC, Vu HH, Nguyen TTC, Ta PQ, Ha HTT, Trinh DT, Bui HTM, Trinh DQ, Van Nguyen K, Le SH, Van Vu K, Van Tran T, Tran HTT, Shrubsole MJ, Ye F, Cai Q, Zheng W, Boffetta P, Shu XO, Luu HN. Findings from the first colorectal cancer screening among 103 542 individuals in Vietnam with systematic review of colorectal cancer screening programs in Asia-Pacific region. Jpn J Clin Oncol 2022; 52:707-715. [PMID: 35383373 PMCID: PMC9264238 DOI: 10.1093/jjco/hyac043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 03/17/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Colorectal cancer is a leading cancer incidence and cause of death worldwide and in Vietnam. Although screening is considered an effective measure to prevent and control colorectal cancer, there is no such effort in Vietnam. METHODS Between 01 January 2018 and 31 October 2019, a population-based colorectal cancer screening program was conducted in Hanoi, Vietnam. A health advocacy campaign and follow-up phone calls were used to enroll residents aged ≥40 years old to complete an immunochemical-fecal occult blood testing. Positive immunochemical-fecal occult blood testing was followed by a colonoscopy. We also conducted a systematic review of the colorectal cancer screening programs in the Asia-Pacific region that used similar approach by searching Ovid Medline and PubMed databases. RESULTS During study period, 103 542 individuals among 672 742 eligible residents attended the screening of whom 81.5% participants finished immunochemical-fecal occult blood testing test and the positive rate was 6.1%. The coverage rate for immunochemical-fecal occult blood testing test was 11.9%. Among 2278 individuals who underwent colonoscopy, 3.5% were histologically diagnosed with cancer, 17.8% with advanced adenomas, and 23.1% with non-advanced adenomas. Males had significantly higher detection rate of advanced adenomas, cancer or ≥ two polyps/tumor than females (P < 0.0001). The systematic review showed that in two-step modality (i.e. immunochemical-fecal occult blood testing/fecal immunochemical test and colonoscopy), the test positive was from 4.1 to 10.6%. Once colonoscopy was performed subsequently, the rate of cancer among positive participants was from 1.7 to 16.4% and that of advanced adenomas was from 7.1 to 23.1%. CONCLUSION We showed that the two-step modality is a promising strategy for colorectal cancer screening in Vietnam that might apply to similar settings with limited resources.
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Affiliation(s)
- Chi Thi-Du Tran
- Vietnam Colorectal Cancer and Polyps Research Program, Vinmec Healthcare System, Hanoi, Vietnam
- College of Health Sciences, VinUniversity (VinUni), Hanoi, Vietnam
- Center of Applied Sciences, Regenerative Medicine and Advanced Technology (CARA), Vinmec Healthcare System, Hanoi, Vietnam
| | - Mai Vu-Tuyet Nguyen
- Vietnam Colorectal Cancer and Polyps Research Program, Vinmec Healthcare System, Hanoi, Vietnam
| | - Mo Thi Tran
- Vietnam Colorectal Cancer and Polyps Research Program, Vinmec Healthcare System, Hanoi, Vietnam
| | - Thuy Thi-Van Tuong
- Vietnam Colorectal Cancer and Polyps Research Program, Vinmec Healthcare System, Hanoi, Vietnam
| | - Quang Hong Tran
- Vietnam Colorectal Cancer and Polyps Research Program, Vinmec Healthcare System, Hanoi, Vietnam
| | - Linh Cu Le
- College of Health Sciences, VinUniversity (VinUni), Hanoi, Vietnam
| | - Huong Thi-Thu Pham
- Department of Gastroenterology, Vinmec International Hospital at Times City, Vinmec Healthcare System, Hanoi, Vietnam
| | - Nam Chi Bui
- Department of Gastroenterology, Vinmec International Hospital at Times City, Vinmec Healthcare System, Hanoi, Vietnam
| | - Hien Huy Vu
- Department of Gastroenterology, Vinmec International Hospital at Times City, Vinmec Healthcare System, Hanoi, Vietnam
| | - Tu Thi-Cam Nguyen
- Department of Gastroenterology, Vinmec International Hospital at Times City, Vinmec Healthcare System, Hanoi, Vietnam
| | - Phuong Que Ta
- Department of Gastroenterology, Vinmec International Hospital at Times City, Vinmec Healthcare System, Hanoi, Vietnam
| | - Hien Thi-Thu Ha
- Department of Histopathology, Vinmec International Hospital at Times City, Vinmec Healthcare System, Hanoi, Vietnam
| | - Dung Tuan Trinh
- Department of Histopathology, Vinmec International Hospital at Times City, Vinmec Healthcare System, Hanoi, Vietnam
- Department of Histopathology, Tam Anh General Hospital, Hanoi, Vietnam
| | - Hanh Thi-My Bui
- Department of Histopathology, Vinmec International Hospital at Times City, Vinmec Healthcare System, Hanoi, Vietnam
| | - Dien Quang Trinh
- Department of Histopathology, Vinmec International Hospital at Times City, Vinmec Healthcare System, Hanoi, Vietnam
| | - Khanh Van Nguyen
- Department of Histopathology, Vinmec International Hospital at Times City, Vinmec Healthcare System, Hanoi, Vietnam
| | - Song Huu Le
- Center of Molecular and Genetic Research, 108 Hospital, Hanoi, Vietnam
| | - Khien Van Vu
- Department of Gastroenterology, 108 Hospital, Hanoi, Vietnam
| | - Thuan Van Tran
- Vietnam Ministry of Health, Hanoi, Vietnam
- Vietnam National Cancer Institute, Vietnam National Cancer Hospital, Hanoi, Vietnam
| | - Huong Thi-Thanh Tran
- Vietnam National Cancer Institute, Vietnam National Cancer Hospital, Hanoi, Vietnam
| | - Martha J Shrubsole
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Fei Ye
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Qiuyin Cai
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Paolo Boffetta
- Stony Brook Cancer Center, Stony Brooke University, Stony Brook, NY, USA
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Xiao-Ou Shu
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Hung N Luu
- UPMC Hillman Cancer Center, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
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25
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Methylated Septin 9 as a Promising Biomarker in the Diagnosis and Recurrence Monitoring of Colorectal Cancer. DISEASE MARKERS 2022; 2022:7087885. [PMID: 35818587 PMCID: PMC9271001 DOI: 10.1155/2022/7087885] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 04/29/2022] [Accepted: 06/01/2022] [Indexed: 12/24/2022]
Abstract
Purpose. The clinical utility of plasma methylated septin 9 (mSEPT9) DNA in screening and recurrence monitoring for colorectal cancer (CRC) is highly promising. The present study was performed to determine the diagnostic value of mSEPT9 in CRC detection and recurrence monitoring in Chinese patients. Methods. Overall, 616 patients newly diagnosed with CRC and 122 individuals with no evidence of disease were recruited from October 1, 2019, to May 31, 2021, at Fujian Medical University Union Hospital. Plasma and serum samples were collected for analyzing mSEPT9, carcinoembryonic antigen (CEA), and carbohydrate antigen-19-9 (CA19-9). Data on clinicopathological characteristics were collected and analyzed. Sensitivity and specificity were calculated to evaluate the diagnostic potential of each marker; the receiver operating characteristic (ROC) curve was applied for the assessment of diagnostic value, and comparisons among mSEPT9, CEA, CA19-9, and their combination were assessed via ROC curves. Results. mSEPT9 achieved an overall sensitivity and specificity of 72.94% and 81.97%, respectively, with an area under the curve (AUC) value of 0.826, which were higher than those of CEA (sensitivity: 43.96%; specificity: 96.72%; AUC: 0.789) and CA19-9 (sensitivity: 14.99%; specificity: 96.61%; AUC: 0.590). The combination of mSEPT9, CEA, and CA19-9 further improved sensitivity, specificity, and AUC value (sensitivity: 78.43%; specificity: 86.07%; AUC: 0.878), respectively. Notably, the mSEPT9 positivity rate was significantly associated with TNM stage, T stage, N stage, tumor size, vascular invasion, and nerve invasion among patients with CRC. A 100% correlation was observed between the positive results of the mSEPT9 test and recurrence or metastasis in patients after therapeutic intervention. Conclusion. Our findings suggest that mSEPT9 may represent a potential biomarker for the diagnosis and prognosis of CRC compared with CEA and CA19-9. Postoperative mSEPT9 status may represent the first noninvasive marker of CRC recurrence or metastasis.
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Jiang HH, Xing SW, Tang X, Chen Y, Lin K, He LW, Lin MB, Tang EJ. Novel multiplex stool-based assay for the detection of early-stage colon cancer in a Chinese population. World J Gastroenterol 2022; 28:2705-2732. [PMID: 35979157 PMCID: PMC9260868 DOI: 10.3748/wjg.v28.i24.2705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 01/14/2022] [Accepted: 05/14/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Stool DNA (sDNA) methylation analysis is a promising, noninvasive approach for colorectal cancer screening; however, reliable biomarkers for detecting early-stage colon cancer (ECC) are lacking, particularly in the Chinese population.
AIM To identify a novel stool-based assay that can improve the effectiveness of ECC screening.
METHODS A blinded case-control study was performed using archived stool samples from 125 ECC patients, and 125 control subjects with normal colonoscopy. The cohort was randomly divided into training and test sets at a 1.5:1 ratio. Targeted bisulfite sequencing (TBSeq) was conducted on five pairs of preoperative and postop-erative sDNA samples from ECC patients to identify DNA methylation biomarkers, which were validated using pyrosequencing. By logistic regression analysis, a multiplex stool-based assay was developed in the training set, and the detection performance was further assessed in the test set and combined set. The χ2 test was used to investigate the association of detection sensitivity with clinico-pathological features.
RESULTS Following TBSeq, three hypermethylated cytosine-guanine sites were selected as biomarkers, including paired box 8, Ras-association domain family 1 and secreted frizzled-related protein 2, which differed between the groups and were involved in important cancer pathways. An sDNA panel containing the three biomarkers was constructed with a logistic model. Receiver operating characteristic (ROC) analysis revealed that this panel was superior to the fecal immunochemical test (FIT) or serum carcinoembryonic antigen for the detection of ECC. We further found that the combination of the sDNA panel with FIT could improve the screening effectiveness. In the combined set, the sensitivity, specificity and area under the ROC curve for this multiplex assay were 80.0%, 93.6% and 0.918, respectively, and the performance remained excellent in the subgroup analysis by tumor stage. In addition, the detection sensitivity did not differ with tumor site, tumor stage, histological differentiation, age or sex, but was significantly higher in T4 than in T1-3 stage tumors (P = 0.041).
CONCLUSION We identified a novel multiplex stool-based assay combining sDNA methylation biomarkers and FIT, which could detect ECC with high sensitivity and specificity throughout the colon, showing a promising application perspective.
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Affiliation(s)
- Hui-Hong Jiang
- Department of General Surgery, Yangpu Hospital, Tongji University, Shanghai 200090, China
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
| | - Si-Wei Xing
- Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University, Shanghai 200090, China
| | - Xuan Tang
- Department of General Surgery, Yangpu Hospital, Tongji University, Shanghai 200090, China
| | - Ying Chen
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University, Shanghai 200090, China
| | - Kang Lin
- Department of General Surgery, Yangpu Hospital, Tongji University, Shanghai 200090, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University, Shanghai 200090, China
| | - Lu-Wei He
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University, Shanghai 200090, China
| | - Mou-Bin Lin
- Department of General Surgery, Yangpu Hospital, Tongji University, Shanghai 200090, China
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University, Shanghai 200090, China
| | - Er-Jiang Tang
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University, Shanghai 200090, China
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Wang L, Liu Y, Zhang D, Xiong X, Hao T, Zhong L, Zhao Y. Diagnostic accuracy of DNA-based SDC2 methylation test in colorectal cancer screening: a meta-analysis. BMC Gastroenterol 2022; 22:314. [PMID: 35754025 PMCID: PMC9235166 DOI: 10.1186/s12876-022-02395-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 06/20/2022] [Indexed: 12/24/2022] Open
Abstract
Background A growing body of research suggests that methylated genes can be used as early diagnostic markers for cancer. Some studies on methylated Syndecan 2 (SDC2) have shown that it has a great diagnostic ability in colorectal cancer. This meta-analysis was aimed to estimate the diagnostic performance of methylated SDC2 as a potential novel biomarker to screen for the colorectal cancer. Methods Two independent researchers conducted a comprehensive literature search to identify all relevant studies on SDC2 methylation for the diagnosis of colorectal cancer from inception to March 1, 2021. By using STATA and Revman software, the data were analyzed using a Bivariate mixed model. The quality of each study was also evaluated. Results A total of 12 studies comprised of 1574 colorectal cancer patients and 1945 healthy people were included in our meta-analysis. Bivariate analysis showed a pooled sensitivity of 0.81 [95% confidence interval (CI) 0.74–0.86], specificity of 0.95 (95% CI 0.93–0.96), positive likelihood ratio of 15.29 (95% CI 10.83–21.60), and negative likelihood ratio of 0.21 (95% CI 0.15–0.27). The diagnostic odds ratio and the area under the summary ROC curve for diagnosing colorectal cancer were 74.42 (95% CI45.44–121.89) and 0.96 (95% CI 0.94–0.97), respectively. For adenomas, the pooled sensitivity and specificity were 0.47 (95% CI 0.34–0.61) and 0.95 (95% CI 0.92–0.97), respectively. Conclusions Our analysis revealed that methylated SDC2 could be considered as a potential novel biomarker to screen for colorectal cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-022-02395-7.
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Affiliation(s)
- Lixing Wang
- Department of Nuclear Medicine, The Second Hospital of Jilin University, Changchun, 130041, China
| | - Yu Liu
- Department of Nuclear Medicine, The Second Hospital of Jilin University, Changchun, 130041, China
| | - Duohan Zhang
- Department of Nuclear Medicine, The Second Hospital of Jilin University, Changchun, 130041, China
| | - Xiaoliang Xiong
- Department of Nuclear Medicine, The Second Hospital of Jilin University, Changchun, 130041, China
| | - Tingting Hao
- Department of Nuclear Medicine, The Second Hospital of Jilin University, Changchun, 130041, China
| | - Lili Zhong
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University, Changchun, 130041, China.
| | - Yinlong Zhao
- Department of Nuclear Medicine, The Second Hospital of Jilin University, Changchun, 130041, China.
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Lu DC, Zhang QF, Li L, Luo XK, Liang B, Lu YH, Hu BL, Jiang HX. Methylated Septin9 has moderate diagnostic value in colorectal cancer detection in Chinese population: a multicenter study. BMC Gastroenterol 2022; 22:232. [PMID: 35546391 PMCID: PMC9097435 DOI: 10.1186/s12876-022-02313-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 04/26/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The detection rate of methylated Septin9 (mSEPT9) in colorectal cancer (CRC) is varied greatly across the studies. This study aimed to evaluate the diagnostic ability of mSEPT9 in CRC, and compare the diagnostic efficacy with fecal immunochemical test (FIT). METHODS 326 subjects from four centers were prospectively recruited, including 179 CRC and 147 non-CRC subjects. The plasma was collected for mSEPT9 and CEA, AFP, CA125, CA153 and CA199 test, and fecal samples for FIT tests. Sensitivity, specificity and area under the curve (AUC) of receiver operating characteristic curve were calculated to evaluate the diagnostic value of each biomarker. RESULTS The positive rate in mSEPT9 and FIT, and the level of CEA, CA125 and CA199 were significantly higher in CRC compared with non-CRC subjects. The mSEPT9 positive rate was not associated with TNM stage and tumor stage. The sensitivity, specificity and AUC of mSEPT9 in diagnostic CRC were 0.77, 0.88 and 0.82, respectively, while the value in FIT was 0.88, 0.80 and 0.83, respectively. mSEPT9 and FIT have higher AUC value than that of CEA, CA125 and CA199. Combination of both mSEPT9 and FIT positive increased sensitivity and AUC to 0.98 and 0.83, respectively, but the specificity was declined. mSEPT9 has a slightly low sensitivity in diagnosis of colon cancer (0.87) compared with rectal cancer (0.93). CONCLUSION mSEPT9 demonstrated moderate diagnostic value in CRC detection, which was similar to the FIT but superior to the CEA, CA125 and CA199. Combination of mSEPT9 and FIT further improved diagnostic sensitivity in CRC. TRIAL REGISTRATION ChiCTR2000038319.
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Affiliation(s)
- Dong-Cheng Lu
- Department of Gastroenterology, First Affiliated Hospital of Guangxi Medical University, Shuangyong Road 6, Nanning, 530021, Guangxi, China
| | - Qi-Fang Zhang
- Department of Gastroenterology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, 541002, China
| | - Li Li
- Department of Gastroenterology, Jiangbin Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
| | - Xian-Ke Luo
- Department of Gastroenterology, Minzu Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530001, China
| | - Bin Liang
- Department of Gastroenterology, First Affiliated Hospital of Guangxi Medical University, Shuangyong Road 6, Nanning, 530021, Guangxi, China
| | - Yi-Han Lu
- Department of Gastroenterology, First Affiliated Hospital of Guangxi Medical University, Shuangyong Road 6, Nanning, 530021, Guangxi, China
| | - Bang-Li Hu
- Department of Research, Guangxi Medical University Cancer Hospital, Hedi Road 71, Nanning, 530021, China.
| | - Hai-Xing Jiang
- Department of Gastroenterology, First Affiliated Hospital of Guangxi Medical University, Shuangyong Road 6, Nanning, 530021, Guangxi, China.
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Takei D, Harada K, Nouso K, Miyahara K, Dohi C, Matsushita H, Kinugasa H, Hiraoka S, Nishimura SI, Okada H. Clinical utility of a serum glycome analysis in patients with colorectal cancer. J Gastroenterol Hepatol 2022; 37:727-733. [PMID: 35064597 DOI: 10.1111/jgh.15781] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 10/12/2021] [Accepted: 01/07/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Serum glycans are known to be good markers for the early diagnosis and prognostic prediction in many cancers. The aims of this study were to reveal the serum glycan changes comprehensively during the process of carcinogenesis from colorectal adenoma (CRA) to colorectal cancer (CRC) and to evaluate the usefulness of the glycan profiles as clinical markers for CRC. METHODS Serum samples were obtained from 80 histologically proven CRC and 36 CRA cases. The levels of glycans in the serum were examined with a comprehensive, quantitative, high-throughput unique glycome analysis, and their diagnostic and prognostic abilities were evaluated. RESULTS Among 34 stably detected glycans, nine were differentially expressed between CRC and CRA. Serum levels of hybrid type glycans were increased in patients with CRC compared with those with CRA (P < 0.001), and both hybrid-type and multi-antennary glycans were significantly increased in advanced cancer cases. The glycan, m/z 1914, showed the highest diagnostic value among the decreased glycans, whereas m/z 1708 showed the highest among the increased glycans. The glycan ratio m/z 1708/1914 showed a higher area under the receiver operating characteristic curve (0.889) than any other single glycan or conventional tumor marker, such as carcinoembryonic antigen (0.766, P = 0.040) and carbohydrate antigen 19-9 (0.615, P < 0.001). High m/z 1708/1914 was also correlated with an advanced cancer stage and short overall survival. CONCLUSION Serum glycans, especially the m/z 1708/1914 ratio, were useful for the diagnosis, staging, and prognosis prediction of CRC.
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Affiliation(s)
- Daisuke Takei
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Keita Harada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Kazuhiro Nouso
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Koji Miyahara
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Chihiro Dohi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroshi Matsushita
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hideaki Kinugasa
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Sakiko Hiraoka
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Shin-Ichiro Nishimura
- Field of Drug Discovery Research, Faculty of Advanced Life Science and Graduate School of Life Science, Hokkaido University, Sapporo, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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Blad N, Palmqvist R, Karling P. Pre-diagnostic faecal calprotectin levels in patients with colorectal cancer: a retrospective study. BMC Cancer 2022; 22:315. [PMID: 35331198 PMCID: PMC8944005 DOI: 10.1186/s12885-022-09440-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 03/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Faecal calprotectin (FC) is a potential biomarker for colorectal cancer (CRC) screening. There is uncertainty if tumor characteristics are associated with FC levels. We investigated how tumor stage and tumor localization influence the extent of FC levels in patients with CRC in clinical practice. METHODS In two cohorts of patients with CRC, we retrospectively analyzed FC tests (CALPRO®) performed within three months prior to diagnosis. One hundred twenty-four patients with CRC were included (mean age 68 years, 44% women). RESULTS Ninety-eight patients with CRC (79%) had a FC ≥ 50 µg/g. FC correlated positively with tumor stage (UICC based on WHO TNM classification) (rs 0.24; p = 0.007) and with CRP levels (rs 0.31, p = 001), and a negatively with B-haemoglobin (rs -0.21; p = 0.019). The patients with right-sided CRC had significantly more often a FC ≥ 50 µg/g than patients with left-sided CRC (92% vs 74% p = 0.027). In a binary logistic regression analysis, tumor stage III/IV (adjusted OR 3.47; CI 1.27-9.42) and right-sided tumor localization (adjusted OR 3.80; CI 1.01-14.3) were associated with FC ≥ 50 µg/g. Tumor stage III/IV (adjusted OR 2.30; CI 1.04-5.10) and acetylsalicylic use (adjusted OR 3.54; CI 1.03-12.2) were associated with FC ≥ 100 µg/g. In a cox regression analysis, a FC ≥ 100 µg/g was not associated with survival (Hazard OR 0.61; CI 0.24-1.52). CONCLUSIONS Elevated pre-diagnostic FC levels were common in patients with CRC in close proximity to diagnosis. Right-sided localization and tumor stage were significantly associated with a rise in FC levels.
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Affiliation(s)
- Nathalie Blad
- Department of Public Health and Clinical Medicine/Medicine, Umeå University, S90185, Umeå, Sweden
| | - Richard Palmqvist
- Department of Medical Biosciences/ Pathology, Umeå University, Umeå, Sweden
| | - Pontus Karling
- Department of Public Health and Clinical Medicine/Medicine, Umeå University, S90185, Umeå, Sweden.
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Konishi Y, Okumura S, Matsumoto T, Itatani Y, Nishiyama T, Okazaki Y, Shibutani M, Ohtani N, Nagahara H, Obama K, Ohira M, Sakai Y, Nagayama S, Hara E. Development and evaluation of a colorectal cancer screening method using machine learning-based gut microbiota analysis. Cancer Med 2022; 11:3194-3206. [PMID: 35318827 PMCID: PMC9385600 DOI: 10.1002/cam4.4671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 01/17/2022] [Accepted: 01/18/2022] [Indexed: 12/02/2022] Open
Abstract
Accumulating evidence indicates that alterations of gut microbiota are associated with colorectal cancer (CRC). Therefore, the use of gut microbiota for the diagnosis of CRC has received attention. Recently, several studies have been conducted to detect the differences in the gut microbiota between healthy individuals and CRC patients using machine learning‐based gut bacterial DNA meta‐sequencing analysis, and to use this information for the development of CRC diagnostic model. However, to date, most studies had small sample sizes and/or only cross‐validated using the training dataset that was used to create the diagnostic model, rather than validated using an independent test dataset. Since machine learning‐based diagnostic models cause overfitting if the sample size is small and/or an independent test dataset is not used for validation, the reliability of these diagnostic models needs to be interpreted with caution. To circumvent these problems, here we have established a new machine learning‐based CRC diagnostic model using the gut microbiota as an indicator. Validation using independent test datasets showed that the true positive rate of our CRC diagnostic model increased substantially as CRC progressed from Stage I to more than 60% for CRC patients more advanced than Stage II when the false positive rate was set around 8%. Moreover, there was no statistically significant difference in the true positive rate between samples collected in different cities or in any part of the colorectum. These results reveal the possibility of the practical application of gut microbiota‐based CRC screening tests.
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Affiliation(s)
- Yusuke Konishi
- Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Japan
| | - Shintaro Okumura
- Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Japan.,The Cancer Institute, Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan.,Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Tomonori Matsumoto
- Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Japan
| | | | | | - Yuki Okazaki
- Osaka City University Graduate School of Medicine, Osaka, Japan
| | | | - Naoko Ohtani
- Osaka City University Graduate School of Medicine, Osaka, Japan
| | | | - Kazutaka Obama
- Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Masaichi Ohira
- Osaka City University Graduate School of Medicine, Osaka, Japan
| | | | - Satoshi Nagayama
- The Cancer Institute Hospital, JFCR, Tokyo, Japan.,Uji-Tokushukai Medical Center, Uji, Japan
| | - Eiji Hara
- Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Japan.,The Cancer Institute, Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan.,Immunology Frontier Research Centre (IFReC), Osaka University, Suita, Japan.,Center for Infectious Disease Education and Research (CiDER), Osaka University, Suita, Japan
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Ballerini P, Contursi A, Bruno A, Mucci M, Tacconelli S, Patrignani P. Inflammation and Cancer: From the Development of Personalized Indicators to Novel Therapeutic Strategies. Front Pharmacol 2022; 13:838079. [PMID: 35308229 PMCID: PMC8927697 DOI: 10.3389/fphar.2022.838079] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 02/09/2022] [Indexed: 12/15/2022] Open
Abstract
Colorectal (CRC) and hepatocellular carcinoma (HCC) are associated with chronic inflammation, which plays a role in tumor development and malignant progression. An unmet medical need in these settings is the availability of sensitive and specific noninvasive biomarkers. Their use will allow surveillance of high-risk populations, early detection, and monitoring of disease progression. Moreover, the characterization of specific fingerprints of patients with nonalcoholic fatty liver disease (NAFLD) without or with nonalcoholic steatohepatitis (NASH) at the early stages of liver fibrosis is necessary. Some lines of evidence show the contribution of platelets to intestinal and liver inflammation. Thus, low-dose Aspirin, an antiplatelet agent, reduces CRC and liver cancer incidence and mortality. Aspirin also produces antifibrotic effects in NAFLD. Activated platelets can trigger chronic inflammation and tissue fibrosis via the release of soluble mediators, such as thromboxane (TX) A2 and tumor growth factor (TGF)-β, and vesicles containing genetic material (including microRNA). These platelet-derived products contribute to cyclooxygenase (COX)-2 expression and prostaglandin (PG)E2 biosynthesis by tumor microenvironment cells, such as immune and endothelial cells and fibroblasts, alongside cancer cells. Enhanced COX-2-dependent PGE2 plays a crucial role in chronic inflammation and promotes tumor progression, angiogenesis, and metastasis. Antiplatelet agents can indirectly prevent the induction of COX-2 in target cells by inhibiting platelet activation. Differently, selective COX-2 inhibitors (coxibs) block the activity of COX-2 expressed in the tumor microenvironment and cancer cells. However, coxib chemopreventive effects are hampered by the interference with cardiovascular homeostasis via the coincident inhibition of vascular COX-2-dependent prostacyclin biosynthesis, resulting in enhanced risk of atherothrombosis. A strategy to improve anti-inflammatory agents' use in cancer prevention could be to develop tissue-specific drug delivery systems. Platelet ability to interact with tumor cells and transfer their molecular cargo can be employed to design platelet-mediated drug delivery systems to enhance the efficacy and reduce toxicity associated with anti-inflammatory agents in these settings. Another peculiarity of platelets is their capability to uptake proteins and transcripts from the circulation. Thus, cancer patient platelets show specific proteomic and transcriptomic expression profiles that could be used as biomarkers for early cancer detection and disease monitoring.
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Affiliation(s)
- Patrizia Ballerini
- Center for Advanced Studies and Technology (CAST), Chieti, Italy
- Department of Innovative Technologies in Medicine and Dentistry, Chieti, Italy
| | - Annalisa Contursi
- Center for Advanced Studies and Technology (CAST), Chieti, Italy
- Department of Neuroscience, Imaging and Clinical Science, G. d’Annunzio University, Chieti, Italy
| | - Annalisa Bruno
- Center for Advanced Studies and Technology (CAST), Chieti, Italy
- Department of Neuroscience, Imaging and Clinical Science, G. d’Annunzio University, Chieti, Italy
| | - Matteo Mucci
- Center for Advanced Studies and Technology (CAST), Chieti, Italy
- Department of Neuroscience, Imaging and Clinical Science, G. d’Annunzio University, Chieti, Italy
| | - Stefania Tacconelli
- Center for Advanced Studies and Technology (CAST), Chieti, Italy
- Department of Neuroscience, Imaging and Clinical Science, G. d’Annunzio University, Chieti, Italy
| | - Paola Patrignani
- Center for Advanced Studies and Technology (CAST), Chieti, Italy
- Department of Neuroscience, Imaging and Clinical Science, G. d’Annunzio University, Chieti, Italy
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Beltrán-García J, Osca-Verdegal R, Mena-Mollá S, Seco-Cervera M, Peiró-Chova L, García-Giménez JL, Laurent-Puig P, Cervantes A. Translational epigenetics in precision medicine of colorectal cancer. EPIGENETICS IN PRECISION MEDICINE 2022:19-41. [DOI: 10.1016/b978-0-12-823008-4.00018-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Role of Biomarkers in the Diagnosis and Treatment of Inflammatory Bowel Disease. Life (Basel) 2021; 11:life11121375. [PMID: 34947906 PMCID: PMC8707558 DOI: 10.3390/life11121375] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 11/28/2021] [Accepted: 12/07/2021] [Indexed: 12/12/2022] Open
Abstract
The number of patients with inflammatory bowel disease (IBD) is increasing worldwide. Endoscopy is the gold standard to assess the condition of IBD. The problem with this procedure is that the burden and cost on the patient are high. Therefore, the identification of a reliable biomarker to replace endoscopy is desired. Biomarkers are used in various situations such as diagnosis of IBD, evaluation of disease activity, prediction of therapeutic effect, and prediction of relapse. C-reactive protein and fecal calprotectin have a lot of evidence as objective biomarkers of disease activity in IBD. The usefulness of the fecal immunochemical test, serum leucine-rich glycoprotein, and urinary prostaglandin E major metabolite have also been reported. Herein, we comprehensively review the usefulness and limitations of biomarkers that can be used in daily clinical practice regarding IBD. To date, no biomarker is sufficiently accurate to replace endoscopy; however, it is important to understand the characteristics of each biomarker and use the appropriate biomarker at the right time in daily clinical practice.
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35
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Low potency of fecal immunological surveillance testing soon after negative colonoscopy or resection of low-risk adenoma in average-risk patients. Eur J Gastroenterol Hepatol 2021; 33:e933-e938. [PMID: 34750324 DOI: 10.1097/meg.0000000000002310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Postcolonoscopy surveillance colonoscopy based on positive fecal occult blood testing (FOBT) is often performed, although its long-term efficacy has not been established. The aim of this study was to clarify the low potency of FOBT surveillance at short intervals after colonoscopy. METHODS Colonoscopy was performed in 1308 average-risk patients, based on positive results of immunological FOBT [fecal immunological test (FIT)]. Patients were stratified according to the length of time since their last colonoscopy and their colonoscopy results [no adenoma or 1-2 small (<10 mm) adenomas]. Tumor detection rates were determined. RESULTS The baseline patients characteristics did not differ between the groups. The advanced lesion detection rate (ALDR) among the patients who had never undergone a colonoscopy was 21.9% [95% confidence interval (CI), 19.1-25.0%]. Among the patients who had no adenoma detected in the previous colonoscopy within the past 5 years, the past 5-10 years and over 10 years, the ALDRs were 2.5% (95% CI, 1.0-5.5%), 4.1% (95% CI, 1.5-9.4%) and 9.3% (95% CI, 3.1-22.2%), respectively. Among the patients who had 1-2 small adenomas, the ALDRs were 7.4% (95% CI, 3.4-14.8%), 12.1% (95% CI, 4.2-27.9%) and 27.8% (95% CI, 12.2-51.2%), respectively. Invasive cancer was not observed in any patients within 5 years since the prior colonoscopy. CONCLUSION In average-risk patients whose prior colonoscopy detected no adenomas or low-risk adenomas, postcolonoscopy surveillance by FIT has a low positive predictive value within a 5-year interval.
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Imperiale TF, Daggy JK, Imler TD, Sherer EA, Kahi CJ, Larson J, Cardwell J, Johnson CS, Ahnen DJ, Antaki F, Ashley C, Baffy G, Dominitz JA, Hou J, Korsten MA, Nagar A, Promrat K, Robertson DJ, Saini S, Shergill A, Smalley WE. Prevalence of Advanced Colorectal Neoplasia in Veterans: Effects of Age, Sex, and Race/Ethnicity. J Clin Gastroenterol 2021; 55:876-883. [PMID: 34049372 DOI: 10.1097/mcg.0000000000001402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 06/29/2020] [Indexed: 12/10/2022]
Abstract
GOAL We sought to quantify the independent effects of age, sex, and race/ethnicity on risk of colorectal cancer (CRC) and advanced neoplasia (AN) in Veterans. STUDY We conducted a retrospective, cross-sectional study of Veterans aged 40 to 80 years who had diagnostic or screening colonoscopy between 2002 and 2009 from 1 of 14 Veterans Affairs Medical Centers. Natural language processing identified the most advanced finding and location (proximal, distal). Logistic regression was used to examine the adjusted, independent effects of age, sex, and race, both overall and in screening and diagnostic subgroups. RESULTS Among 90,598 Veterans [mean (SD) age 61.7 (9.4) y, 5.2% (n=4673) were women], CRC and AN prevalence was 1.3% (n=1171) and 8.9% (n=8081), respectively. Adjusted CRC risk was higher for diagnostic versus screening colonoscopy [odds ratio (OR)=3.79; 95% confidence interval (CI), 3.19-4.50], increased with age, was numerically (but not statistically) higher for men overall (OR=1.53; 95% CI, 0.97-2.39) and in the screening subgroup (OR=2.24; 95% CI, 0.71-7.05), and was higher overall for Blacks and Hispanics, but not in screening. AN prevalence increased with age, and was present in 9.2% of men and 3.9% of women [adjusted OR=1.90; 95% CI, 1.60-2.25]. AN risk was 11% higher in Blacks than in Whites overall (OR=1.11; 95% CI, 1.04-1.20), was no different in screening, and was lower in Hispanics (OR=0.74; 95% CI, 0.55-0.98). Women had more proximal CRC (63% vs. 39% for men; P=0.03), but there was no difference in proximal AN (38.3% for both genders). CONCLUSIONS Age and race were associated with AN and CRC prevalence. Blacks had a higher overall prevalence of both CRC and AN, but not among screenings. Men had increased risk for AN, while women had a higher proportion of proximal CRC. These findings may be used to tailor when and how Veterans are screened for CRC.
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Affiliation(s)
- Thomas F Imperiale
- Center for Innovation, Health Services Research and Development, Richard L. Roudebush VA Medical Center
- Department of Medicine, Division of Gastroenterology and Hepatology
- Regenstrief Institute Inc., Indianapolis, IN
| | | | - Timothy D Imler
- Department of Medicine, Division of Gastroenterology and Hepatology
- Regenstrief Institute Inc., Indianapolis, IN
| | | | - Charles J Kahi
- Center for Innovation, Health Services Research and Development, Richard L. Roudebush VA Medical Center
- Department of Medicine, Division of Gastroenterology and Hepatology
| | - Jason Larson
- Center for Innovation, Health Services Research and Development, Richard L. Roudebush VA Medical Center
| | - Jon Cardwell
- Center for Innovation, Health Services Research and Development, Richard L. Roudebush VA Medical Center
| | | | - Dennis J Ahnen
- Department of Medicine, University of Colorado and Denver VAMC, Boulder, CO
| | - Fadi Antaki
- Department of Medicine, John D. Dingell VAMC, Wayne State University, Detroit
| | | | - Gyorgy Baffy
- Department of Gastroenterology, VA Boston Healthcare System, Harvard Medical School, Boston, MA
| | - Jason A Dominitz
- Department of Medicine, VA Puget Sound Health Care System, University of Washington, Seattle, WA
| | - Jason Hou
- Department of Medicine, Michael E. DeBakey VAMC, Baylor University, Houston, TX
| | - Mark A Korsten
- James J. Peters VA Medical Center, Icahn School of Medicine at Mt. Sinai, Bronx, NY
| | - Anil Nagar
- West Haven VA Medical Center, Yale University School of Medicine, West Haven, CT
| | - Kittichai Promrat
- Section of Gastroenterology, Providence VAMC, Alpert Medical School of Brown University, Providence, RI
| | - Douglas J Robertson
- Geisel School of Medicine at Dartmouth and The Dartmouth Institute and the White River Junction VAMC, White River Junction, VT
| | - Sameer Saini
- VA HSR&D Center for Clinical Management Research
- Department of Internal Medicine and Institute of Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI
| | - Amandeep Shergill
- Department of Medicine, San Francisco VA Medical Center, University of California at San Francisco, San Francisco, CA
| | - Walter E Smalley
- Department of Medicine, VA Tennessee Valley Healthcare System and Vanderbilt University, Nashville, TN. ✠ Dennis J. Ahnen deceased
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Results of Compliant Participation in Five Rounds of Fecal Immunochemical Test Screening for Colorectal Cancer. Clin Gastroenterol Hepatol 2021; 19:2361-2369. [PMID: 32827723 DOI: 10.1016/j.cgh.2020.08.038] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 08/13/2020] [Accepted: 08/17/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We investigated the magnitude and temporal patterns of the decreasing trend in main performance measures of fecal immunochemical test (FIT) screening for colorectal cancer (CRC) observed in second and subsequent rounds. METHODS We followed up 494,187 participants from the first round of a regional biennial FIT screening program in Italy (cut-off value for positivity, 20 μg hemoglobin/g feces) for 5 total rounds (2005-2016). At each round, only compliant participants were eligible. Performance measures from the first, third, fourth, and fifth rounds were compared with those from the second round (the first incidence round) using rate ratios from multivariate Poisson regression models and relative risk ratios from multinomial logistic regression models. RESULTS Between the second and the third rounds, a significant 20% to 30% decrease was found in the proportion of men with a positive FIT result (from 5.2% to 4.3%) and in detection rates of advanced adenoma (from 13.4 to 10.2 per 1000), CRC (from 1.7 to 1.4 per 1000), and advanced neoplasia (from 15.1 to 11.6 per 1000). Positive predictive values (PPVs) decreased by 10% or less between the second and third rounds. Detection rates and PPVs for adenoma stabilized by the fourth and fifth rounds. The PPVs for advanced adenoma, CRC, and advanced neoplasia decreased slightly in men and women by the fourth and fifth rounds. The detection rate of proximal colon cancer stabilized after the second round, whereas the detection rate of distal colon cancer decreased until the fourth round in men (from 0.7 to 0.3 per 1000), and the fifth round in women. CONCLUSIONS These findings support the notion that FIT screening prevents progression of a subset of advanced adenomas. Screening intensity could be modulated based on results from previous rounds, with a risk-based strategy.
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Cheng YC, Wu PH, Chen YJ, Yang CH, Huang JL, Chou YC, Chang PK, Wen CC, Jao SW, Huang HH, Tsai YH, Pai TW. Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test. Genes (Basel) 2021; 12:1539. [PMID: 34680934 PMCID: PMC8535797 DOI: 10.3390/genes12101539] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 09/26/2021] [Accepted: 09/27/2021] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide in 2020. Colonoscopy and the fecal immunochemical test (FIT) are commonly used as CRC screening tests, but both types of tests possess different limitations. Recently, liquid biopsy-based DNA methylation test has become a powerful tool for cancer screening, and the detection of abnormal DNA methylation in stool specimens is considered as an effective approach for CRC screening. The aim of this study was to develop a novel approach in biomarker selection based on integrating primary biomarkers from genome-wide methylation profiles and secondary biomarkers from CRC comorbidity analytics. A total of 125 differential methylated probes (DMPs) were identified as primary biomarkers from 352 genome-wide methylation profiles. Among them, 51 biomarkers, including 48 hypermethylated DMPs and 3 hypomethylated DMPs, were considered as suitable DMP candidates for CRC screening tests. After comparing with commercial kits, three genes (ADHFE1, SDC2, and PPP2R5C) were selected as candidate epigenetic biomarkers for CRC screening tests. Methylation levels of these three biomarkers were significantly higher for patients with CRC than normal subjects. The sensitivity and specificity of integrating methylated ADHFE1, SDC2, and PPP2R5C for CRC detection achieved 84.6% and 92.3%, respectively. Through an integrated approach using genome-wide DNA methylation profiles and electronic medical records, we could design a biomarker panel that allows for early and accurate noninvasive detection of CRC using stool samples.
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Affiliation(s)
- Yi-Chiao Cheng
- Division of Colon and Rectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan; (Y.-C.C.); (P.-H.W.); (P.-K.C.); (C.-C.W.); (S.-W.J.)
| | - Po-Hsien Wu
- Division of Colon and Rectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan; (Y.-C.C.); (P.-H.W.); (P.-K.C.); (C.-C.W.); (S.-W.J.)
| | - Yen-Ju Chen
- Department of Computer Science and Information Engineering, National Taipei University of Technology, Taipei 10608, Taiwan; (Y.-J.C.); (Y.-H.T.)
| | - Cing-Han Yang
- Department of Computer Science and Engineering, National Taiwan Ocean University, Keelung 20224, Taiwan; (C.-H.Y.); (J.-L.H.)
| | - Jhen-Li Huang
- Department of Computer Science and Engineering, National Taiwan Ocean University, Keelung 20224, Taiwan; (C.-H.Y.); (J.-L.H.)
| | - Yu-Ching Chou
- School of Public Health, National Defense Medical Center, Taipei 11490, Taiwan;
| | - Pi-Kai Chang
- Division of Colon and Rectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan; (Y.-C.C.); (P.-H.W.); (P.-K.C.); (C.-C.W.); (S.-W.J.)
| | - Chia-Cheng Wen
- Division of Colon and Rectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan; (Y.-C.C.); (P.-H.W.); (P.-K.C.); (C.-C.W.); (S.-W.J.)
| | - Shu-Wen Jao
- Division of Colon and Rectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan; (Y.-C.C.); (P.-H.W.); (P.-K.C.); (C.-C.W.); (S.-W.J.)
| | - Hsin-Hui Huang
- Department of Biochemistry and Molecular Cell Biology, School of Medicine, Taipei Medical University, Taipei 11042, Taiwan;
| | - Yi-Hsuan Tsai
- Department of Computer Science and Information Engineering, National Taipei University of Technology, Taipei 10608, Taiwan; (Y.-J.C.); (Y.-H.T.)
| | - Tun-Wen Pai
- Department of Computer Science and Information Engineering, National Taipei University of Technology, Taipei 10608, Taiwan; (Y.-J.C.); (Y.-H.T.)
- Department of Computer Science and Engineering, National Taiwan Ocean University, Keelung 20224, Taiwan; (C.-H.Y.); (J.-L.H.)
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Abstract
Mortality from colorectal cancer is reduced through screening and early detection; moreover, removal of neoplastic lesions can reduce cancer incidence. While understanding of the risk factors, pathogenesis, and precursor lesions of colorectal cancer has advanced, the cause of the recent increase in cancer among young adults is largely unknown. Multiple invasive, semi- and non-invasive screening modalities have emerged over the past decade. The current emphasis on quality of colonoscopy has improved the effectiveness of screening and prevention, and the role of new technologies in detection of neoplasia, such as artificial intelligence, is rapidly emerging. The overall screening rates in the US, however, are suboptimal, and few interventions have been shown to increase screening uptake. This review provides an overview of colorectal cancer, the current status of screening efforts, and the tools available to reduce mortality from colorectal cancer.
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Affiliation(s)
- Priyanka Kanth
- Division of Gastroenterology, University of Utah, Salt Lake City, UT, USA
- Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
| | - John M Inadomi
- Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA
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Bjørsum-Meyer T, Baatrup G, Koulaouzidis A. Colon Capsule Endoscopy as a Diagnostic Adjunct in Patients with Symptoms from the Lower Gastrointestinal Tract. Diagnostics (Basel) 2021; 11:diagnostics11091671. [PMID: 34574011 PMCID: PMC8467213 DOI: 10.3390/diagnostics11091671] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 09/08/2021] [Accepted: 09/09/2021] [Indexed: 02/07/2023] Open
Abstract
Prompted by the core idea of wireless capsule endoscopy as a painless gastrointestinal examination, and the easy adoption of small bowel capsule endoscopy, the armamentarium of the capsule-based imaging platforms has grown to include colon capsule devices as well [...].
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Affiliation(s)
- Thomas Bjørsum-Meyer
- Department of Surgery, Odense University Hospital, 5700 Svendborg, Denmark;
- Department of Clinical Research, University of Southern Denmark, 5230 Odense M, Denmark
- Correspondence: ; Tel.: +45-27896080
| | - Gunnar Baatrup
- Department of Surgery, Odense University Hospital, 5700 Svendborg, Denmark;
- Department of Clinical Research, University of Southern Denmark, 5230 Odense M, Denmark
| | - Anastasios Koulaouzidis
- Department of Social Medicine & Public Health, Pomeranian Medical University, 70-204 Szczecin, Poland;
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Kobayashi N, Oike T, Kubo N, Miyasaka Y, Mizukami T, Sato H, Adachi A, Katoh H, Kawamura H, Ohno T. Colorectal Cancer Screening Outcomes of 2412 Prostate Cancer Patients Considered for Carbon Ion Radiotherapy. Cancers (Basel) 2021; 13:cancers13174481. [PMID: 34503291 PMCID: PMC8431542 DOI: 10.3390/cancers13174481] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 09/03/2021] [Accepted: 09/03/2021] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) screening is effective for detecting cancer in average-risk adults. For prostate cancer (PCa) patients considered for carbon ion radiotherapy (CIRT), pre-treatment CRC screening is performed empirically to avoid post-treatment colonoscopic manipulation. However, the outcomes of screening this population remain unclear. Here, we compared the outcomes of routine pre-CIRT CRC screening of 2412 PCa patients at average risk for CRC with data from two published datasets: the Japan National Cancer Registry (JNCR) and a series of 17 large-scale screening studies analyzing average-risk adults. The estimated prevalence rate was calculated using the pooled sensitivity elucidated by a previous meta-analysis. Consequently, 28 patients (1.16%) were diagnosed with CRC. CRC morbidity was significantly associated with high pre-treatment levels of prostate-specific antigen (p = 0.023). The screening positivity rate in this study cohort exceeded the annual incidence reported in the JNCR for most age brackets. Furthermore, the estimated prevalence rate in this study cohort (1.46%) exceeded that reported in all 17 large-scale studies, making the result an outlier (p = 0.005). These data indicate the possibility that the prevalence of CRC in PCa patients is greater than that in general average-risk adults, warranting further research in a prospective setting.
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Affiliation(s)
- Nao Kobayashi
- Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showamachi, Maebashi 371-8511, Japan; (N.K.); (N.K.); (A.A.); (T.O.)
| | - Takahiro Oike
- Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showamachi, Maebashi 371-8511, Japan; (N.K.); (N.K.); (A.A.); (T.O.)
- Gunma University Heavy Ion Medical Center, 3-39-22 Showa-machi, Maebashi 371-8511, Japan; (Y.M.); (H.S.); (H.K.)
- Correspondence: ; Tel.: +81-27-220-8383
| | - Nobuteru Kubo
- Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showamachi, Maebashi 371-8511, Japan; (N.K.); (N.K.); (A.A.); (T.O.)
| | - Yuhei Miyasaka
- Gunma University Heavy Ion Medical Center, 3-39-22 Showa-machi, Maebashi 371-8511, Japan; (Y.M.); (H.S.); (H.K.)
| | - Tatsuji Mizukami
- Department of Radiology, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan;
| | - Hiro Sato
- Gunma University Heavy Ion Medical Center, 3-39-22 Showa-machi, Maebashi 371-8511, Japan; (Y.M.); (H.S.); (H.K.)
| | - Akiko Adachi
- Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showamachi, Maebashi 371-8511, Japan; (N.K.); (N.K.); (A.A.); (T.O.)
| | - Hiroyuki Katoh
- Department of Radiation Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama 241-8515, Japan;
| | - Hidemasa Kawamura
- Gunma University Heavy Ion Medical Center, 3-39-22 Showa-machi, Maebashi 371-8511, Japan; (Y.M.); (H.S.); (H.K.)
| | - Tatsuya Ohno
- Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showamachi, Maebashi 371-8511, Japan; (N.K.); (N.K.); (A.A.); (T.O.)
- Gunma University Heavy Ion Medical Center, 3-39-22 Showa-machi, Maebashi 371-8511, Japan; (Y.M.); (H.S.); (H.K.)
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Okuda Y, Shimura T, Iwasaki H, Katano T, Kitagawa M, Nishigaki R, Fukusada S, Natsume M, Tanaka M, Nishie H, Ozeki K, Yamada T, Kataoka H. Serum Exosomal Dicer Is a Useful Biomarker for Early Detection of Differentiated Gastric Adenocarcinoma. Digestion 2021; 102:640-649. [PMID: 33049740 DOI: 10.1159/000510993] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 08/16/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIM A recent basic study identified that Dicer is contained in exosomes derived from cancer cells and plays crucial roles in microRNA maturation and cancer development. Based on this novel basic concept, we analyzed the usefulness of serum exosomal Dicer as a diagnostic biomarker for gastrointestinal cancers. METHODS Enrolled participants (691) were categorized into 3 groups: gastric cancer (GC) cohort, 183 patients (90 healthy controls (HCs) and 93 GC patients); esophageal cancer (EC) cohort, 115 patients (90 HCs and 25 EC patients); and colorectal cancer (CRC) cohort, 188 patients (92 HCs and 96 CRC patients) after age- and sex matching using the propensity score. The quality of isolated serum exosomes was validated with an electron microscope, particle size analyzer, and exosome marker, CD63. RESULTS Serum exosomal Dicer was significantly higher in the GC group than in the HC group (p = 0.004), whereas no significant differences were found in both EC and CRC cohorts. Serum exosomal Dicer was significantly higher in only differentiated gastric adenocarcinoma and not in the undifferentiated type. Moreover, serum exosomal Dicer showed no significant differences regardless of Helicobacter pylori (H. pylori) status. The biomarker panel combining serum exosomal Dicer with H. pylori status distinguished between HC and differentiated GC patients with an area under the curve (AUC) of 0.762. As for early-stage diagnosis, this combination distinguished between HC and stage I differentiated GC with an AUC = 0.758. CONCLUSIONS Serum exosomal Dicer is a potential noninvasive diagnostic biomarker for early detection of differentiated gastric adenocarcinoma.
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Affiliation(s)
- Yusuke Okuda
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takaya Shimura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan,
| | - Hiroyasu Iwasaki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takahito Katano
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Mika Kitagawa
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Ruriko Nishigaki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shigeki Fukusada
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Makoto Natsume
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Mamoru Tanaka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hirotada Nishie
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Keiji Ozeki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | | | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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Sin RWY, Foo DCC, Iyer DN, Fan MSY, Li X, Lo OSH, Law WL, Ng L. A Pilot Study Investigating the Expression Levels of Pluripotency-Associated Genes in Rectal Swab Samples for Colorectal Polyp and Cancer Diagnosis and Prognosis. Stem Cells Int 2021; 2021:4139528. [PMID: 34335790 PMCID: PMC8324395 DOI: 10.1155/2021/4139528] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 12/11/2020] [Accepted: 06/09/2021] [Indexed: 02/06/2023] Open
Abstract
Change in gene expression is inevitable in cancer development. With more studies demonstrating the contributions of cancer stem cells (CSCs) in colorectal cancer (CRC) development, this study is aimed at investigating whether rectal swab specimen serves as a tool for detection of dysregulation of CSC or stem cell (SC) markers and at evaluating its potential as a new promising screening method for high-risk patients. Expression levels of 15 pluripotency-associated genes were assessed by quantitative PCR in 53 rectal swab specimens referred for endoscopic screening. Dysregulated genes and joint panels based on such genes were examined for their diagnostic potentials for both polyp and CRC. Out of 15 genes, Oct4, CD26, c-MYC, and CXCR4 showed significantly differential expression among normal, polyp, and CRC patients. A panel of Oct4 and CD26 showed an AUC value of 0.80 (p = 0.003) in identifying CRC patients from polyp/normal subjects, with sensitivity and specificity of 84.6% and 69.2%. A panel of c-MYC and CXCR4 achieved CRC/polyp identification with an AUC value of 0.79 (p = 0.002), with a sensitivity of 82.8% and specificity of 80.0%. The sensitivity for polyp and CRC was 80.0% and 85.7%, respectively. Further analysis showed that higher c-MYC and CXCR4 level was detected in normal subjects who developed polyps after 5-6 years, in comparison with subjects with no lesion developed, and the AUC of the c-MYC and CXCR4 panel increased to 0.88 (p < 0.001), with sensitivity and specificity of 84.4% and 92.3%, respectively, when these patients were included in the polyp group. This study suggests that the Oct4 and CD26 panel is a promising biomarker for distinguishing CRC from normal and polyp patients, whereas the c-MYC and CXCR4 panel may identify polyp and CRC from normal individuals.
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Affiliation(s)
- Ryan Wai-Yan Sin
- Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Dominic Chi-Chung Foo
- Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Deepak Narayanan Iyer
- Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - May Sau-Yee Fan
- Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Xue Li
- Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Oswens Siu-Hung Lo
- Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Wai-Lun Law
- Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Lui Ng
- Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
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Imperiale TF, Monahan PO, Stump TE, Ransohoff DF. Derivation and validation of a predictive model for advanced colorectal neoplasia in asymptomatic adults. Gut 2021; 70:1155-1161. [PMID: 32994311 DOI: 10.1136/gutjnl-2020-321698] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 08/27/2020] [Accepted: 08/30/2020] [Indexed: 12/26/2022]
Abstract
OBJECTIVE Knowing risk for advanced colorectal neoplasia (AN) could help patients and providers choose among screening tests, improving screening efficiency and uptake. We created a risk prediction model for AN to help decide which test might be preferred, a use not considered for existing models. DESIGN Average-risk 50-to-80-year olds undergoing first-time screening colonoscopy were recruited from endoscopy units in Indiana. We measured sociodemographic and physical features, medical and family history and lifestyle factors and linked these to the most advanced finding. We derived a risk equation on two-thirds of the sample and assigned points to each variable to create a risk score. Scores with comparable risks were collapsed into risk categories. The model and score were tested on the remaining sample. RESULTS Among 3025 subjects in the derivation set (mean age 57.3 (6.5) years; 52% women), AN prevalence was 9.4%. The 13-variable model (c-statistic=0.77) produced three risk groups with AN risks of 1.5% (95% CI 0.72% to 2.74%), 7.06% (CI 5.89% to 8.38%) and 27.26% (CI 23.47% to 31.30%) in low-risk, intermediate-risk and high-risk groups (p value <0.001), containing 23%, 59% and 18% of subjects, respectively. In the validation set of 1475 subjects (AN prevalence of 8.4%), model performance was comparable (c-statistic=0.78), with AN risks of 2.73% (CI 1.25% to 5.11%), 5.57% (CI 4.12% to 7.34%) and 25.79% (CI 20.51% to 31.66%) in low-risk, intermediate-risk and high-risk subgroups, respectively (p<0.001), containing proportions of 23%, 59% and 18%. CONCLUSION Among average-risk persons, this model estimates AN risk with high discrimination, identifying a lower risk subgroup that may be screened non-invasively and a higher risk subgroup for which colonoscopy may be preferred. The model could help guide patient-provider discussions of screening options, may increase screening adherence and conserve colonoscopy resources.
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Affiliation(s)
- Thomas F Imperiale
- Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA .,Center for Innovation, Health Services Research and Development, Richard L Roudebush VA Medical Center, Indianapolis, IN, USA.,The Regenstrief Institute Inc, Indianapolis, IN, USA
| | - Patrick O Monahan
- Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Timothy E Stump
- Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - David F Ransohoff
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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Druce P, Calanzani N, Snudden C, Milley K, Boscott R, Behiyat D, Martinez-Gutierrez J, Saji S, Oberoi J, Funston G, Messenger M, Walter FM, Emery J. Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Lower Gastrointestinal Cancers: A Systematic Review and Meta-Analysis. Adv Ther 2021; 38:3032-3065. [PMID: 33907946 PMCID: PMC8078393 DOI: 10.1007/s12325-021-01645-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 01/30/2021] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Lower gastrointestinal (GI) cancers are a major cause of cancer deaths worldwide. Prognosis improves with earlier diagnosis, and non-invasive biomarkers have the potential to aid with early detection. Substantial investment has been made into the development of biomarkers; however, studies are often carried out in specialist settings and few have been evaluated for low-prevalence populations. METHODS We aimed to identify novel biomarkers for the detection of lower GI cancers that have the potential to be evaluated for use in primary care. MEDLINE, Embase, Emcare and Web of Science were systematically searched for studies published in English from January 2000 to October 2019. Reference lists of included studies were also assessed. Studies had to report on measures of diagnostic performance for biomarkers (single or in panels) used to detect colorectal or anal cancers. We included all designs and excluded studies with fewer than 50 cases/controls. Data were extracted from published studies on types of biomarkers, populations and outcomes. Narrative synthesis was used, and measures of specificity and sensitivity were meta-analysed where possible. RESULTS We identified 142 studies reporting on biomarkers for lower GI cancers, for 24,844 cases and 45,374 controls. A total of 378 unique biomarkers were identified. Heterogeneity of study design, population type and sample source precluded meta-analysis for all markers except methylated septin 9 (mSEPT9) and pyruvate kinase type tumour M2 (TuM2-PK). The estimated sensitivity and specificity of mSEPT9 was 80.6% (95% CI 76.6-84.0%) and 88.0% (95% CI 79.1-93.4%) respectively; TuM2-PK had an estimated sensitivity of 81.6% (95% CI 75.2-86.6%) and specificity of 80.1% (95% CI 76.7-83.0%). CONCLUSION Two novel biomarkers (mSEPT9 and TuM2-PK) were identified from the literature with potential for use in lower-prevalence populations. Further research is needed to validate these biomarkers in primary care for screening and assessment of symptomatic patients.
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Affiliation(s)
- Paige Druce
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Melbourne, VIC, Australia.
| | - Natalia Calanzani
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Claudia Snudden
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Kristi Milley
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Melbourne, VIC, Australia
| | - Rachel Boscott
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Dawnya Behiyat
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Javiera Martinez-Gutierrez
- Department of Family Medicine, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Smiji Saji
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Jasmeen Oberoi
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Melbourne, VIC, Australia
| | - Garth Funston
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Mike Messenger
- Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | - Fiona M Walter
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Melbourne, VIC, Australia
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Jon Emery
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Melbourne, VIC, Australia
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
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Toyoshima O, Yamaji Y, Nishizawa T, Yoshida S, Yamada T, Kurokawa K, Obata M, Kondo R, Toba M, Koike K. Priority stratification for colonoscopy based on two-sample faecal immunochemical test screening: results from a cross-sectional study at an endoscopy clinic in Japan. BMJ Open 2021; 11:e046055. [PMID: 34011594 PMCID: PMC8137156 DOI: 10.1136/bmjopen-2020-046055] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 04/20/2021] [Accepted: 04/29/2021] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVES Little has been reported on the yield and characteristics of colorectal neoplasia detected by the two-sample faecal immunochemical test (FIT), particularly the difference between subjects with two-positive results on the two-sample FIT and those with one-positive results. We aimed to assess risk stratification among patients with positive two-sample FIT to prioritise colonoscopy. DESIGN A retrospective cross-sectional study. SETTING A single-centre, representative endoscopy clinic in Japan. PARTICIPANTS Consecutive patients who underwent colonoscopy were enrolled. Indications for colonoscopy included two-positive results on the two-sample FIT (FIT (+/+)), one-positive results on the two-sample FIT (FIT (+/-)), and other reasons (non-FIT group, including presence of symptoms, screening or surveillance). PRIMARY AND SECONDARY OUTCOME MEASURES Primary outcomes were detection rates of colorectal cancers, including in situ (all cancers) and invasive cancers, based on the indications for colonoscopy. Secondary outcomes were cancer features, such as location, size, T stage and histological subtype. RESULTS Of the 8724 patients, 264 underwent colonoscopy following FIT (+/+), 1018 following FIT (+/-) and 7442 for reasons other than positive FIT. Detection rates of all (and invasive) cancers in the FIT (+/+), FIT (+/-) and non-FIT groups were 12.1% (8.3%), 1.9% (0.3%) and 0.4% (0.2%), respectively. The cancer detection rates were much higher in the FIT (+/+) group than in the FIT (+/-) group, which in turn had higher rates than the non-FIT group. Moreover, the FIT (+/+) group showed more advanced T stages on tumour, node, metastasis (TNM) classification (Tis/T1/T2/T3/T4: 10/7/4/10/1) than the FIT (+/-) group (16/1/2/0/0, p<0.001). CONCLUSIONS Two-positive results for two-sample FIT showed a much higher yield for more advanced colorectal cancers than the one-positive result. High priority for diagnostic colonoscopy should be assigned to patients with two-positive-FIT results.
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Affiliation(s)
- Osamu Toyoshima
- Department of Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yutaka Yamaji
- Health Development Center, Tokyo Pharmaceutical Industry Health Insurance Society, Tokyo, Japan
| | - Toshihiro Nishizawa
- Department of Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology and Hepatology, International University of Health and Welfare, Narita Hosapital, Narita, Japan
| | - Shuntaro Yoshida
- Department of Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
| | - Tomoharu Yamada
- Department of Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ken Kurokawa
- Department of Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Miho Obata
- Department of Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryo Kondo
- Department of Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
| | - Masahito Toba
- Department of Gastroenterology, Toba Clinic, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Lin JS, Perdue LA, Henrikson NB, Bean SI, Blasi PR. Screening for Colorectal Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 2021; 325:1978-1998. [PMID: 34003220 DOI: 10.1001/jama.2021.4417] [Citation(s) in RCA: 336] [Impact Index Per Article: 84.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
IMPORTANCE Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the US. OBJECTIVE To systematically review the effectiveness, test accuracy, and harms of screening for CRC to inform the US Preventive Services Task Force. DATA SOURCES MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2015, to December 4, 2019; surveillance through March 26, 2021. STUDY SELECTION English-language studies conducted in asymptomatic populations at general risk of CRC. DATA EXTRACTION AND SYNTHESIS Two reviewers independently appraised the articles and extracted relevant study data from fair- or good-quality studies. Random-effects meta-analyses were conducted. MAIN OUTCOMES AND MEASURES Colorectal cancer incidence and mortality, test accuracy in detecting cancers or adenomas, and serious adverse events. RESULTS The review included 33 studies (n = 10 776 276) on the effectiveness of screening, 59 (n = 3 491 045) on the test performance of screening tests, and 131 (n = 26 987 366) on the harms of screening. In randomized clinical trials (4 trials, n = 458 002), intention to screen with 1- or 2-time flexible sigmoidoscopy vs no screening was associated with a decrease in CRC-specific mortality (incidence rate ratio, 0.74 [95% CI, 0.68-0.80]). Annual or biennial guaiac fecal occult blood test (gFOBT) vs no screening (5 trials, n = 419 966) was associated with a reduction of CRC-specific mortality after 2 to 9 rounds of screening (relative risk at 19.5 years, 0.91 [95% CI, 0.84-0.98]; relative risk at 30 years, 0.78 [95% CI, 0.65-0.93]). In observational studies, receipt of screening colonoscopy (2 studies, n = 436 927) or fecal immunochemical test (FIT) (1 study, n = 5.4 million) vs no screening was associated with lower risk of CRC incidence or mortality. Nine studies (n = 6497) evaluated the test accuracy of screening computed tomography (CT) colonography, 4 of which also reported the test accuracy of colonoscopy; pooled sensitivity to detect adenomas 6 mm or larger was similar between CT colonography with bowel prep (0.86) and colonoscopy (0.89). In pooled values, commonly evaluated FITs (14 studies, n = 45 403) (sensitivity, 0.74; specificity, 0.94) and stool DNA with FIT (4 studies, n = 12 424) (sensitivity, 0.93; specificity, 0.85) performed better than high-sensitivity gFOBT (2 studies, n = 3503) (sensitivity, 0.50-0.75; specificity, 0.96-0.98) to detect cancers. Serious harms of screening colonoscopy included perforations (3.1/10 000 procedures) and major bleeding (14.6/10 000 procedures). CT colonography may have harms resulting from low-dose ionizing radiation. It is unclear if detection of extracolonic findings on CT colonography is a net benefit or harm. CONCLUSIONS AND RELEVANCE There are several options to screen for colorectal cancer, each with a different level of evidence demonstrating its ability to reduce cancer mortality, its ability to detect cancer or precursor lesions, and its risk of harms.
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Affiliation(s)
- Jennifer S Lin
- Kaiser Permanente Evidence-based Practice Center, Center for Health Research, Kaiser Permanente, Portland, Oregon
| | - Leslie A Perdue
- Kaiser Permanente Evidence-based Practice Center, Center for Health Research, Kaiser Permanente, Portland, Oregon
| | - Nora B Henrikson
- Kaiser Permanente Evidence-based Practice Center, Center for Health Research, Kaiser Permanente, Portland, Oregon
| | - Sarah I Bean
- Kaiser Permanente Evidence-based Practice Center, Center for Health Research, Kaiser Permanente, Portland, Oregon
| | - Paula R Blasi
- Kaiser Permanente Evidence-based Practice Center, Center for Health Research, Kaiser Permanente, Portland, Oregon
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Fecal DNA Testing of TWIST1 Methylation Identifies Patients With Advanced Colorectal Adenoma Missed by Fecal Immunochemical Test for Hemoglobin. Clin Transl Gastroenterol 2021; 11:e00176. [PMID: 32467409 PMCID: PMC7339193 DOI: 10.14309/ctg.0000000000000176] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION We have reported previously that fecal DNA testing of TWIST1 methylation in combination with the fecal immunochemical test for hemoglobin (FIT) (combination test) is useful for colorectal neoplasia screening. In this study, using larger sample sizes, we studied the clinical performance of the combination test for the detection of colorectal neoplasia and, especially, advanced colorectal adenoma. METHODS We performed a prospective study in which FIT, fecal DNA testing of TWIST1 methylation, and colonoscopy were performed on 372 patients with colorectal neoplasia and 71 subjects without colorectal neoplasia. We assessed the individual clinical performance of each of FIT and fecal DNA testing of TWIST1 methylation and of the combination test for the detection of colorectal neoplasia including advanced adenoma based on morphologic subtypes. RESULTS The FIT alone had a sensitivity of 7.5% (3/40) for nonadvanced adenoma, 32.3% (41/127) for advanced adenoma, and 93.7% (192/205) for colorectal cancer and a specificity of 87.3% (62/71). The combination test had a sensitivity of 35.0% (14/40) for nonadvanced adenoma, 68.5% (87/127) for advanced adenoma, and 95.6% (196/205) for colorectal cancer and a specificity of 80.3% (57/71). For morphological subtypes of advanced adenoma, the sensitivity of FIT was only 28.2% (20/71) for polypoid type and 16.1% (5/31) for nonpolypoid type, whereas the combination test increased the sensitivities to 64.8% (46/71) and 71.0% (22/31), respectively. DISCUSSION The combination of the fecal DNA test with FIT seemed to be useful to detect colorectal neoplasia and, especially, advanced adenoma of the nonpolypoid type.
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Redwood DG, Dinh TA, Kisiel JB, Borah BJ, Moriarty JP, Provost EM, Sacco FD, Tiesinga JJ, Ahlquist DA. Cost-Effectiveness of Multitarget Stool DNA Testing vs Colonoscopy or Fecal Immunochemical Testing for Colorectal Cancer Screening in Alaska Native People. Mayo Clin Proc 2021; 96:1203-1217. [PMID: 33840520 DOI: 10.1016/j.mayocp.2020.07.035] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 06/17/2020] [Accepted: 07/13/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To estimate the cost-effectiveness of multitarget stool DNA testing (MT-sDNA) compared with colonoscopy and fecal immunochemical testing (FIT) for Alaska Native adults. PATIENTS AND METHODS A Markov model was used to evaluate the 3 screening test effects over 40 years. Outcomes included colorectal cancer (CRC) incidence and mortality, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). The study incorporated updated evidence on screening test performance and adherence and was conducted from December 15, 2016, through November 6, 2019. RESULTS With perfect adherence, CRC incidence was reduced by 52% (95% CI, 46% to 56%) using colonoscopy, 61% (95% CI, 57% to 64%) using annual FIT, and 66% (95% CI, 63% to 68%) using MT-sDNA. Compared with no screening, perfect adherence screening extends life by 0.15, 0.17, and 0.19 QALYs per person with colonoscopy, FIT, and MT-sDNA, respectively. Colonoscopy is the most expensive strategy: approximately $110 million more than MT-sDNA and $127 million more than FIT. With imperfect adherence (best case), MT-sDNA resulted in 0.12 QALYs per person vs 0.05 and 0.06 QALYs per person by FIT and colonoscopy, respectively. Probabilistic sensitivity analyses supported the base-case analysis. Under varied adherence scenarios, MT-sDNA either dominates or is cost-effective (ICERs, $1740-$75,868 per QALY saved) compared with FIT and colonoscopy. CONCLUSION Each strategy reduced costs and increased QALYs compared with no screening. Screening by MT-sDNA results in the largest QALY savings. In Markov model analysis, screening by MT-sDNA in the Alaska Native population was cost-effective compared with screening by colonoscopy and FIT for a wide range of adherence scenarios.
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Kim SY, Kim HS, Kim YT, Lee JK, Park HJ, Kim HM, Kang DR. Colonoscopy Versus Fecal Immunochemical Test for Reducing Colorectal Cancer Risk: A Population-Based Case-Control Study. Clin Transl Gastroenterol 2021; 12:e00350. [PMID: 33928919 PMCID: PMC8088829 DOI: 10.14309/ctg.0000000000000350] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 03/12/2021] [Indexed: 12/22/2022] Open
Abstract
INTRODUCTION Use of colonoscopy or the fecal immunochemical test (FIT) for colorectal cancer (CRC) prevention is supported by previous studies. However, there is little specific evidence regarding comparative effectiveness of colonoscopy or FIT for reducing CRC risk. In this study, we compared the association of CRC risk with colonoscopy and FIT using a nationwide database. METHODS This population-based case-control study used colonoscopy and FIT claims data from the Korean National Health Insurance System from 2002 to 2013. Data were analyzed from 61,221 patients with newly diagnosed CRC (case group) and 306,099 individuals without CRC (control group). Multivariable logistic regression models were used to evaluate the association between CRC and colonoscopy or FIT. RESULTS Colonoscopy was associated with a reduced subsequent CRC risk (adjusted odds ratio [OR] 0.29). Stronger associations were found between colonoscopy and distal CRC, compared with proximal CRC (0.24 vs 0.47). In an analysis stratified by sex, the association was weaker in female subjects compared with male subjects (0.33 vs 0.27). Any FIT exposure was associated with CRC risk with an OR of 0.74; this association was stronger for distal cancer. As the frequency of cumulative FIT assessments increased (from 1 to ≥5), the OR of FIT exposure for CRC gradually decreased from 0.81 to 0.45. DISCUSSION The association of colonoscopy or FIT with reduced CRC risk was stronger for distal CRC than for proximal CRC. FIT showed less CRC risk reduction than colonoscopy. However, as the frequency of cumulative FIT assessments increased, the association with CRC prevention became stronger.
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Affiliation(s)
- Su Young Kim
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hyun-Soo Kim
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Yun Tae Kim
- Center of Biomedical Data Science, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Jung Kuk Lee
- Center of Biomedical Data Science, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hong Jun Park
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hee Man Kim
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Dae Ryoung Kang
- Center of Biomedical Data Science, Yonsei University Wonju College of Medicine, Wonju, Korea
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