|
1
|
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. [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.
Collapse
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
| |
Collapse
|
|
2
|
Carvalho B, de Klaver W, van Wifferen F, van Lanschot MCJ, van Wetering AJP, van der Zander QEW, Lemmens M, Bolijn AS, Tijssen M, Delis-van Diemen P, Buekers N, Daenen K, van der Meer J, van Mulligen PG, Hijmans BS, de Ridder S, Meiqari L, Bierkens M, van der Hulst RWM, Kuyvenhoven JPH, van Berkel AM, Depla ACTM, van Leerdam ME, Jansen JM, Wientjes CA, Straathof JWA, Keulen ETP, Ramsoekh D, Moons LMG, Zacherl M, Masclee AAM, de Wit M, Greuter MJE, van Engeland M, Dekker E, Coupé VMH, Meijer GA. Stool-Based Testing for Post-Polypectomy Colorectal Cancer Surveillance Safely Reduces Colonoscopies: The MOCCAS Study. Gastroenterology 2025; 168:121-135.e16. [PMID: 39218164 DOI: 10.1053/j.gastro.2024.08.022] [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: 08/10/2023] [Revised: 07/23/2024] [Accepted: 08/05/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND & AIMS Colonoscopy-based surveillance to prevent colorectal cancer (CRC) causes substantial burden for patients and health care. Stool tests may help to reduce surveillance colonoscopies by limiting colonoscopies to individuals at increased risk of advanced neoplasia. METHODS This cross-sectional observational study included individuals aged 50-75 years with surveillance indication. Before bowel preparation, participants collected samples for a multitarget stool DNA test and 2 fecal immunochemical tests (FITs). Test accuracy was calculated for all surveillance indications. For the post-polypectomy indication only, which is the most common and is associated with a relatively low CRC risk, long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer (ASCCA) model. Stool-based strategies were simulated to tune each test's positivity threshold to obtain strategies at least as effective as colonoscopy surveillance. RESULTS There were 3453 individuals with results for all stool tests and colonoscopy; 2226 had previous polypectomy, 1003 had previous CRC, and 224 had a familial risk. Areas under the receiver operating characteristic curve for advanced neoplasia were 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test, 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR (Eiken Chemical Co, Tokyo, Japan) and 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold (Sentinel, Milan, Italy). Stool-based post-polypectomy surveillance strategies at least as effective as colonoscopy surveillance reduced the number of colonoscopies by 15%-41% and required 5.6-9.5 stool tests over a person's lifetime. Multitarget stool DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs. CONCLUSIONS This study found that stool-based post-polypectomy surveillance strategies can be safe and cost-effective, with potential to reduce the number of colonoscopies by up to 41%. CLINICALTRIALS gov, Number: NCT02715141.
Collapse
Affiliation(s)
- Beatriz Carvalho
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
| | - Willemijn de Klaver
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, The Netherlands
| | - Francine van Wifferen
- Department of Epidemiology and Data Science, Amsterdam University Medical Center, location Vrije Universiteit, Amsterdam, The Netherlands
| | - Meta C J van Lanschot
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, The Netherlands
| | - Alouisa J P van Wetering
- Department of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Quirine E W van der Zander
- Department of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Margriet Lemmens
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Anne S Bolijn
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Marianne Tijssen
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | | | - Nikkie Buekers
- Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Kathleen Daenen
- Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Jaleesa van der Meer
- Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands
| | | | - Brenda S Hijmans
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Sander de Ridder
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Lana Meiqari
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Mariska Bierkens
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - René W M van der Hulst
- Department of Gastroenterology and Hepatology, Spaarne Gasthuis, Haarlem, The Netherlands
| | - Johan P H Kuyvenhoven
- Department of Gastroenterology and Hepatology, Spaarne Gasthuis, Haarlem, The Netherlands
| | - Annemarie M van Berkel
- Department of Gastroenterology and Hepatology, Noordwest Ziekenhuis, Alkmaar, The Netherlands
| | - Annekatrien C T M Depla
- Department of Gastroenterology and Hepatology, Slotervaartziekenhuis, Amsterdam, The Netherlands
| | - Monique E van Leerdam
- Department of Gastroenterology and Hepatology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Jeroen M Jansen
- Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - Caroline A Wientjes
- Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - Jan W A Straathof
- Department of Gastroenterology and Hepatology, Maxima Medisch Centrum, Veldhoven, The Netherlands
| | - Eric T P Keulen
- Department of Gastroenterology and Hepatology, Zuyderland Medisch Centrum, Sittard-Geleen, The Netherlands
| | - Dewkoemar Ramsoekh
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, location Vrije Universiteit, Amsterdam, The Netherlands
| | - Leon M G Moons
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - Ad A M Masclee
- Department of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Meike de Wit
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Marjolein J E Greuter
- Department of Epidemiology and Data Science, Amsterdam University Medical Center, location Vrije Universiteit, Amsterdam, The Netherlands
| | - Manon van Engeland
- Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, The Netherlands
| | - Veerle M H Coupé
- Department of Epidemiology and Data Science, Amsterdam University Medical Center, location Vrije Universiteit, Amsterdam, The Netherlands
| | - Gerrit A Meijer
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
| |
Collapse
|
|
3
|
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.
Collapse
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.
| |
Collapse
|
|
4
|
Randel KR, Botteri E, de Lange T, Schult AL, Eskeland SL, El‐Safadi B, Norvard ER, Bolstad N, Bretthauer M, Hoff G, Holme Ø. Performance of Faecal Immunochemical Testing for Colorectal Cancer Screening at Varying Positivity Thresholds. Aliment Pharmacol Ther 2025; 61:122-131. [PMID: 39373173 PMCID: PMC11636076 DOI: 10.1111/apt.18314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 04/07/2024] [Accepted: 09/19/2024] [Indexed: 10/08/2024]
Abstract
BACKGROUND The positivity thresholds of faecal immunochemical testing (FIT) in colorectal cancer (CRC) screening vary between countries. AIMS To explore the trade-off between colonoscopies performed, adverse events and lesions detected at different FIT thresholds in a Norwegian CRC screening trial. METHODS We included first participation in biennial FIT screening for 47,265 individuals aged 50-74 years. Individuals with FIT > 15 μg Hb/g faeces were referred for colonoscopy. We estimated the number of colonoscopies, adverse events, screen-detected CRCs, advanced adenomas and serrated lesions expected at FIT thresholds currently or recently used in other European countries ranging between 20 and 150 μg/g. RESULTS At the 15 μg/g threshold (Norway), 3705 participants underwent colonoscopy, of whom 203 had CRC, 1119 advanced adenomas and 256 advanced serrated lesions. Using a 47 μg/g threshold, 1826 (49.3%) individuals would have undergone colonoscopy, and 154 (75.9%) would have been diagnosed with CRC, 702 (62.7%) with advanced adenoma and 128 (50.0%) with advanced serrated lesion compared to the 15 μg/g threshold. At 150 μg/g, the corresponding figures would have been 838 (22.6%) undergoing colonoscopy, 114 (56.2%) with CRC, 345 (30.8%) advanced adenoma and 54 (21.1%) advanced serrated lesions. The detection rate of stage I CRC was 0.22% at 15 μg/g and 0.11% at 150 μg/g. Post-colonoscopy bleeding rates were 0.8% and 1.7%, respectively. CONCLUSIONS Increasing the FIT threshold reduces colonoscopy demand, but substantially decreases lesion detection and unfavourably changes CRC stage distribution. The risk of adverse events at colonoscopy increased with FIT threshold, requiring country-specific information on adverse events. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT01538550.
Collapse
Affiliation(s)
- Kristin Ranheim Randel
- Department of Research and DevelopmentTelemark HospitalSkienNorway
- Institute of Health and SocietyUniversity of OsloOsloNorway
- Section for Colorectal Cancer Screening, Cancer Registry of NorwayNorwegian Institute of Public HealthOsloNorway
| | - Edoardo Botteri
- Section for Colorectal Cancer Screening, Cancer Registry of NorwayNorwegian Institute of Public HealthOsloNorway
- Department of Research, Cancer Registry of NorwayNorwegian Institute of Public HealthOsloNorway
| | - Thomas de Lange
- Department of MedicineSahlgrenska University Hospital‐MölndalRegion Västra GötalandSweden
- Department of Molecular and Clinical Medicine, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
| | - Anna Lisa Schult
- Section for Colorectal Cancer Screening, Cancer Registry of NorwayNorwegian Institute of Public HealthOsloNorway
- Department of MedicineVestre Viken Hospital Trust BærumGjettumNorway
| | | | | | - Espen R. Norvard
- Department of PathologyVestre Viken Hospital Trust DrammenDrammenNorway
| | - Nils Bolstad
- Department of Medical BiochemistryOslo University HospitalOsloNorway
| | - Michael Bretthauer
- Department of Transplantation MedicineOslo University HospitalOsloNorway
- Clinical Effectiveness Research Group, Institute of Health and SocietyUniversity of OsloOsloNorway
| | - Geir Hoff
- Department of Research and DevelopmentTelemark HospitalSkienNorway
- Section for Colorectal Cancer Screening, Cancer Registry of NorwayNorwegian Institute of Public HealthOsloNorway
| | - Øyvind Holme
- Institute of Health and SocietyUniversity of OsloOsloNorway
- Department of MedicineSørlandet Hospital KristiansandKristiansandNorway
| |
Collapse
|
|
5
|
Young GP, Benton SC, Bresalier RS, Chiu HM, Dekker E, Fraser CG, Frasa MAM, Halloran SP, Hoffmeister M, Parry S, Selby K, Senore C, Singh H, Symonds EL. Fecal Immunochemical Test Positivity Thresholds: An International Survey of Population-Based Screening Programs. Dig Dis Sci 2024:10.1007/s10620-024-08664-7. [PMID: 39528850 DOI: 10.1007/s10620-024-08664-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 09/23/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND The fecal immunochemical test for hemoglobin (FIT) is now a widely used non-invasive test in population-based organized screening programs for colorectal neoplasia. The positivity thresholds of tests currently in use are based on the fecal hemoglobin concentration (f-Hb), but the rationale for the adopted thresholds are not well documented. To understand current global usage of FIT in screening programs we conducted an international survey of the brands of FIT used, the f-Hb positivity threshold applied and the rationale for the choice. METHODS All members of the World Endoscopy Organization CRC Screening Committee were invited to complete an eight-element initial electronic survey exploring the key aims. Responses were obtained from 63 individuals, representing 38 specific locations in 28 countries. A follow-up survey on technical issues was offered to the 38 locations, with replies from 17 sites in 13 countries. RESULTS In-use quantitative FIT were provided by four main manufacturers; Minaris Medical (2 countries), Eiken Chemical Company/Polymedco (21), Alfresa Pharma (2) and Sentinel Diagnostics (4). Of the 38 screening sites, 15 used the threshold of 20 µg hemoglobin/g feces, while thresholds ranged between 8.5 and 120 ug/g in the remainder. Seven explanations were given for adopted FIT thresholds; maximizing the sensitivity for colorectal neoplasia (n = 23) was the most common followed by the availability of colonoscopy resources (n = 18). Predictive value, specificity, and cost effectiveness were less frequently reported as the rationale. Nine sites found it necessary to change the threshold that they had initially selected. CONCLUSIONS This international survey has documented the wide range of FIT positivity thresholds that are in current use. Quantitative FITs enable programs to achieve the desired program outcomes within available resource constraints by adjusting the positivity threshold. This supports the need for enabling positivity threshold adjustment of emerging new screening tests based on novel predictive biomarkers, rather than providing inflexible test endpoints.
Collapse
Affiliation(s)
- Graeme P Young
- Flinders University, Adelaide, SA, Australia.
- Flinders Cancer Research, Flinders University, Adelaide, SA, 5042, Australia.
| | - Sally C Benton
- NHS Bowel Cancer Screening South of England Hub, Guildford, England, UK
| | | | | | | | | | | | | | | | - Susan Parry
- University of Auckland, Auckland, New Zealand
| | - Kevin Selby
- University Center for Primary Care and Public Health (Unisanté), Lausanne, Switzerland
| | - Carlo Senore
- University hospital Città della salute e della Scienza, Turin, Italy
| | | | - Erin L Symonds
- Flinders University, Adelaide, SA, Australia
- Flinders Medical Centre, Adelaide, SA, Australia
| |
Collapse
|
|
6
|
Young GP, Senore C, Schoengold R, Laven-Law G, Saito H, Symonds EL. An Adjustable Positivity Threshold for Non-invasive Screening Tests for Colorectal Neoplasms Can Improve Screening Program Effectiveness and Feasibility. Dig Dis Sci 2024:10.1007/s10620-024-08657-6. [PMID: 39384709 DOI: 10.1007/s10620-024-08657-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 09/19/2024] [Indexed: 10/11/2024]
Abstract
BACKGROUND In two-step population screening for colorectal cancer (CRC), a simple non-invasive test, commonly a fecal immunochemical test for hemoglobin (FIT), is first undertaken to predict, based on the fecal hemoglobin concentration (f-Hb), who is more likely to have colorectal neoplasia and needs colonoscopy. AIM To evaluate the importance of being able to adjust the f-Hb threshold that triggers follow-up colonoscopy (the "positivity threshold"), we evaluated the predictive value of f-Hb for colorectal neoplasia and its implications for the configuration of new non-invasive tests. METHODS A literature review was conducted on the use of quantitative FIT to select the positivity threshold, followed by using f-Hb from a large population to model how adjusting the positivity threshold enabled achievement of the desired program outcomes in a feasible manner. RESULTS The literature review and the modeling found that while the f-Hb positivity threshold is predictive for colorectal neoplasia across a wide range of f-Hb, there is a complex relationship between program outcomes and f-Hb. The threshold determines not just clinical accuracy (including true- and false-positive results for CRC and/or advanced precursor lesions), but also the colonoscopy workload. A lower f-Hb threshold is associated with a higher sensitivity for neoplasia but a lower specificity and a heavier load of follow-up colonoscopies. Consequently, the threshold determines a program's impact on population CRC mortality and incidence, but also its feasibility and cost-effectiveness within a health-care system. DISCUSSION We are entering a new era of non-invasive screening tests, where multiple biomarkers found in biological samples such as blood as well as feces, are being developed and evaluated. These typically specify a non-transparent algorithm, developed with machine learning, to provide a predictive dichotomous positive/negative result with a fixed associated clinical accuracy and colonoscopy workload. This will restrict use of new tests in jurisdictions where the accuracy and workload implications do not match the desired screening program outcomes. CONCLUSION However, similar to flexible FIT positivity thresholds, it would be ideal if new tests also provide capacity for screening program providers to select the positivity threshold that delivers their desired screening outcomes in a feasible manner. How marketing, distribution and reimbursement of non-invasive tests are approved, funded and implemented varies widely across jurisdictions and must be taken into account.
Collapse
Affiliation(s)
- Graeme P Young
- Flinders Cancer Research, Flinders University, Bedford Park, Adelaide, SA, 5042, Australia.
| | - Carlo Senore
- University hospital Città della salute e della Scienza, Turin, Italy
| | | | - Geri Laven-Law
- Flinders Cancer Research, Flinders University, Bedford Park, Adelaide, SA, 5042, Australia
| | | | - Erin L Symonds
- Flinders Cancer Research, Flinders University, Bedford Park, Adelaide, SA, 5042, Australia
- Bowel Health Service, Flinders Medical Centre, Adelaide, SA, Australia
| |
Collapse
|
|
7
|
Levy BT, Xu Y, Daly JM, Hoffman RM, Dawson JD, Shokar NK, Zuckerman MJ, Molokwu J, Reuland DS, Crockett SD. Comparative Performance of Common Fecal Immunochemical Tests : A Cross-Sectional Study. Ann Intern Med 2024; 177:1350-1360. [PMID: 39222513 DOI: 10.7326/m24-0080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Despite widespread use of fecal immunochemical tests (FITs) for colorectal cancer (CRC) screening, data to guide test selection are limited. OBJECTIVE To compare the performance characteristics of 5 commonly used FITs, using colonoscopy as the reference standard. DESIGN Cross-sectional study. (ClinicalTrials.gov: NCT03264898). SETTING Three U.S. academic medical centers and affiliated endoscopy units. PARTICIPANTS Patients aged 50 to 85 years undergoing screening or surveillance colonoscopy. INTERVENTION Participants completed 5 different FITs before their colonoscopy, including 4 qualitative tests (Hemoccult ICT, Hemosure iFOB, OC-Light S FIT, QuickVue iFOB) and 1 quantitative test (OC-Auto FIT, which was run at the manufacturer's threshold for positivity of >100 ng/mL). MEASUREMENTS The primary outcome was test performance (sensitivity and specificity) for each of the 5 FITs for advanced colorectal neoplasia (ACN), defined as advanced polyps or CRC. Positivity rates, positive and negative predictive values, and rates of unevaluable tests were compared. Multivariable models were used to identify factors affecting sensitivity. RESULTS A total of 3761 participants were enrolled, with a mean age of 62.1 years (SD, 7.8); 63.2% of participants were female, 5.7% were Black, 86.4% were White, and 28.7% were Hispanic. There were 320 participants with ACN (8.5%), including 9 with CRC (0.2%). The test positivity rate varied 4-fold (3.9% to 16.4%) across FITs. Rates of unevaluable FITs ranged from 0.2% to 2.5%. The sensitivity for ACN varied from 10.1% to 36.7%, and specificity varied from 85.5% to 96.6%. Differences in sensitivity between FITs were all statistically significantly different except between Hemosure iFOB and QuickVue iFOB, and specificity differences were all statistically significantly different from one another. In addition to FIT brand, distal location of ACN was also associated with higher FIT sensitivity. LIMITATION The study did not assess the programmatic sensitivity of annual FIT. CONCLUSION Although considered a single class, FITs have varying test performance for detecting ACN and should not be considered interchangeable. PRIMARY FUNDING SOURCE National Institutes of Health.
Collapse
Affiliation(s)
- Barcey T Levy
- University of Iowa Carver College of Medicine; University of Iowa College of Public Health; and Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa (B.T.L.)
| | - Yinghui Xu
- University of Iowa Carver College of Medicine, Iowa City, Iowa (Y.X., J.M.D.)
| | - Jeanette M Daly
- University of Iowa Carver College of Medicine, Iowa City, Iowa (Y.X., J.M.D.)
| | - Richard M Hoffman
- University of Iowa Carver College of Medicine, and Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa (R.M.H.)
| | - Jeffrey D Dawson
- University of Iowa College of Public Health, Iowa City, Iowa (J.D.D.)
| | - Navkiran K Shokar
- Dell Medical School, University of Texas at Austin, Austin, Texas, and Texas Tech University Health Sciences Center, El Paso, Texas (N.K.S.)
| | - Marc J Zuckerman
- Texas Tech University Health Sciences Center, El Paso, Texas (M.J.Z., J.M.)
| | - Jennifer Molokwu
- Texas Tech University Health Sciences Center, El Paso, Texas (M.J.Z., J.M.)
| | - Daniel S Reuland
- University of North Carolina School of Medicine, Chapel Hill, North Carolina (D.S.R.)
| | - Seth D Crockett
- University of North Carolina School of Medicine, Chapel Hill, North Carolina; Oregon Health & Science University, Portland, Oregon; and Portland VA Medical Center, Portland, Oregon (S.D.C.)
| |
Collapse
|
|
8
|
Zarandi-Nowroozi M, Taghiakbari M, Barkun A, Pohl H, Nauche B, Chagnon M, von Renteln D. Effect of fecal immunochemical test cut-off levels on adenoma detection rate: a systematic review and meta-analysis. Scand J Gastroenterol 2024; 59:882-892. [PMID: 38775234 DOI: 10.1080/00365521.2024.2356649] [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: 12/04/2023] [Revised: 04/16/2024] [Accepted: 04/23/2024] [Indexed: 07/30/2024]
Abstract
BACKGROUND Adenoma detection rate (ADR) is higher after a positive fecal immunochemical test (FIT) compared to direct screening colonoscopy. OBJECTIVE This meta-analysis evaluated how ADR, the rates of advanced adenoma detection (AADR), colorectal cancer detection (CDR), and sessile serrated lesion detection (SSLDR) are affected by different FIT positivity thresholds. METHODS We searched MEDLINE, EMBASE, CINAHL, and EBM Reviews databases for studies reporting ADR, AADR, CDR, and SSLDR according to different FIT cut-off values in asymptomatic average-risk individuals aged 50-74 years old. Data were stratified according to sex, age, time to colonoscopy, publication year, continent, and FIT kit type. Study quality, heterogeneity, and publication bias were assessed. RESULTS Overall, 4280 articles were retrieved and fifty-eight studies were included (277,661 FIT-positive colonoscopies; mean cecal intubation 96.3%; mean age 60.8 years; male 52.1%). Mean ADR was 56.1% (95% CI 53.4 - 58.7%), while mean AADR, CDR, and SSLDR were 27.2% (95% CI 24.4 - 30.1%), 5.3% (95% CI 4.7 - 6.0%), and 3.0% (95% CI 1.7 - 4.6%), respectively. For each 20 μg Hb/g increase in FIT cut-off level, ADR increased by 1.54% (95% CI 0.52 - 2.56%, p < 0.01), AADR by 3.90% (95% CI 2.76 - 5.05%, p < 0.01) and CDR by 1.46% (95% CI 0.66 - 2.24%, p < 0.01). Many detection rates were greater amongst males and Europeans. CONCLUSIONS ADRs in FIT-positive colonoscopies are influenced by the adopted FIT positivity threshold, and identified targets, importantly, proved to be higher than most current societal recommendations.
Collapse
Affiliation(s)
- Melissa Zarandi-Nowroozi
- Division of Gastroenterology, University of Montreal Hospital Center (CHUM), Montreal, Quebec, Canada
| | - Mahsa Taghiakbari
- Department of Gastroenterology, University of Montreal Hospital Research Center (CRCHUM), Montreal, Quebec, Canada
| | - Alan Barkun
- Division of Gastroenterology and Hepatology, McGill University Health Centre, McGill University, Montreal, Quebec, Canada
| | - Heiko Pohl
- Dartmouth Geisel School of Medicine, Hanover, NH, USA
- Section of Gastroenterology and Hepatology, VA White River Junction, White River Junction, VT, USA
| | - Bénédicte Nauche
- Department of Library, University of Montreal Hospital Center (CHUM), Montreal, Quebec, Canada
| | - Miguel Chagnon
- Department of Mathematics and Statistics, University of Montreal, Montreal, Quebec, Canada
| | - Daniel von Renteln
- Division of Gastroenterology, University of Montreal Hospital Center (CHUM), Montreal, Quebec, Canada
| |
Collapse
|
|
9
|
Contran N, Arrigoni G, Battisti I, D'Incà R, Angriman I, Franchin C, Scapellato ML, Padoan A, Moz S, Aita A, Savarino E, Lorenzon G, Zingone F, Spolverato G, Pucciarelli S, Nordi E, Galozzi P, Basso D. Colorectal cancer and inflammatory bowel diseases share common salivary proteomic pathways. Sci Rep 2024; 14:17711. [PMID: 39085299 PMCID: PMC11291686 DOI: 10.1038/s41598-024-68400-z] [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: 06/09/2023] [Accepted: 07/22/2024] [Indexed: 08/02/2024] Open
Abstract
Inflammatory bowels diseases (IBD) are high risk conditions for colorectal cancer (CRC). The discovery of IBD and CRC noninvasive protein/peptide biomarkers using saliva and feces was the aim of this study involving 20 controls, 25 IBD (12 Crohn's Disease-CD), 37 CRC. By untargeted proteomic (LTQ-Orbitrap/MS), a total of 152 proteins were identified in saliva. Absent in controls, 73 proteins were present in both IBD and CRC, being mainly related to cell-adhesion, cadherin-binding and enzyme activity regulation (g-Profiler). Among the remaining 79 proteins, 14 were highly expressed in CD and 11 in CRC. These proteins clustered in DNA replication/expression and innate/adaptive immunity. In stool, endogenous peptides from 30 different proteins were identified, two being salivary and CD-associated: Basic Proline-rich Protein 1 (PRBs) and Acidic Proline-rich Phosphoprotein. Biological effects of the PRBs-related peptides GQ-15 and GG-17 found in CD stool were evaluated using CRC cell lines. These peptides induced cell proliferation and activated Erk1/2, Akt and p38 pathways. In conclusion, the salivary proteome unveiled DNA stability and immunity clusters shared between IBD and CRC. Salivary PRB-derived peptides, enriched in CD stool, stimulate CRC cell proliferation and the pro-oncogenic RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways suggesting a potential involvement of PRBs in IBD and cancer pathogenesis.
Collapse
Affiliation(s)
- Nicole Contran
- Department of Medicine (DIMED), University of Padova, 35128, Padova, Italy.
| | - Giorgio Arrigoni
- Department of Biomedical Sciences (DBS), University of Padova, 35128, Padova, Italy
| | - Ilaria Battisti
- Department of Biomedical Sciences (DBS), University of Padova, 35128, Padova, Italy
| | - Renata D'Incà
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, 35128, Padova, Italy
| | - Imerio Angriman
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, 35128, Padova, Italy
| | - Cinzia Franchin
- Department of Biomedical Sciences (DBS), University of Padova, 35128, Padova, Italy
| | - Maria L Scapellato
- Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padova, 35128, Padova, Italy
| | - Andrea Padoan
- Department of Medicine (DIMED), University of Padova, 35128, Padova, Italy
| | - Stefania Moz
- Department of Medicine (DIMED), University of Padova, 35128, Padova, Italy
| | - Ada Aita
- Department of Medicine (DIMED), University of Padova, 35128, Padova, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, 35128, Padova, Italy
| | - Greta Lorenzon
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, 35128, Padova, Italy
| | - Fabiana Zingone
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, 35128, Padova, Italy
| | - Gaya Spolverato
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, 35128, Padova, Italy
| | - Salvatore Pucciarelli
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, 35128, Padova, Italy
| | - Evelyn Nordi
- Department of Medicine (DIMED), University of Padova, 35128, Padova, Italy
| | - Paola Galozzi
- Department of Medicine (DIMED), University of Padova, 35128, Padova, Italy
| | - Daniela Basso
- Department of Medicine (DIMED), University of Padova, 35128, Padova, Italy
| |
Collapse
|
|
10
|
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.
Collapse
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
| |
Collapse
|
|
11
|
Ribe SG, Botteri E, Løberg M, Randel KR, Kalager M, Nilsen JA, Gulichsen EH, Holme Ø. Impact of time between faecal immunochemical tests in colorectal cancer screening on screening results: A natural experiment. Int J Cancer 2023; 152:1414-1424. [PMID: 36346118 PMCID: PMC10098820 DOI: 10.1002/ijc.34351] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 09/27/2022] [Accepted: 10/17/2022] [Indexed: 11/11/2022]
Abstract
Repeated rounds of faecal immunochemical testing (FIT) for occult blood is a common method for screening for colorectal cancer (CRC). However, the time interval between FIT rounds is not thoroughly investigated. In a CRC screening trial in South-Eastern Norway, individuals were invited for biennial FIT between 2012 and 2019. The positivity threshold was >15 mcg haemoglobin/g faeces (mcg/g). Due to organizational challenges, the interval between screening rounds randomly varied between 1.5 and 3.5 years, forming a natural experiment. We investigated the detection rate of CRC and advanced neoplasia (AN: CRC or advanced adenoma) at the subsequent round (FIT2 ), according to the faecal haemoglobin concentration (f-Hb) at the initial screening round (FIT1 ), and time between the two screening rounds. 18 522 individuals with negative FIT1 who attended FIT2 were included in this study. 245 AN were detected at FIT2 , of which 34 were CRC. The CRC detection rate at FIT2 for participants with FIT1 = 0 mcg/g was 0.09% while it was 0.28% for participant with 0 > FIT1 ≤ 15 mcg/g; odds ratio (OR) 3.22, 95% CI 1.49-6.95. For each 3 months' increment between FITs, the OR for detecting CRC was 1.33 (95% CI 0.98-1.79), while the OR was 1.13 (1.02-1.26) for AN. Individuals with FIT1 -value of 0 mcg/g, had a lower AN detection rate compared with participants with 0 > FIT1 ≤ 15 mcg/g, irrespective of time between tests. Although CRC and AN detection rates increase with increasing time interval between FITs, individuals with undetectable f-Hb at first screen have substantially lower risk of CRC at the next screening round compared with individuals with detectable f-Hb.
Collapse
Affiliation(s)
- Sara G Ribe
- Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway.,Center for Cancer Treatment, Sørlandet Hospital, Kristiansand, Norway.,Clinical Effectiveness Research Group, Institute for Health and Society, University of Oslo, Oslo, Norway
| | - Edoardo Botteri
- Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway.,Clinical Effectiveness Research Group, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Magnus Løberg
- Clinical Effectiveness Research Group, Institute for Health and Society, University of Oslo, Oslo, Norway.,Department of Research, Cancer Registry of Norway, Oslo, Norway
| | - Kristin R Randel
- Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway
| | - Mette Kalager
- Clinical Effectiveness Research Group, Institute for Health and Society, University of Oslo, Oslo, Norway.,Clinical Effectiveness Research Group, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | | | | | - Øyvind Holme
- Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway.,Clinical Effectiveness Research Group, Institute for Health and Society, University of Oslo, Oslo, Norway.,Department of Medicine, Sørlandet Hospital, Kristiansand, Norway
| |
Collapse
|
|
12
|
Gu Y, Duan B, Sha J, Zhang R, Fan J, Xu X, Zhao H, Niu X, Geng Z, Gu J, Huang B, Ren S. Serum IgG N-glycans enable early detection and early relapse prediction of colorectal cancer. Int J Cancer 2023; 152:536-547. [PMID: 36121650 DOI: 10.1002/ijc.34298] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 09/05/2022] [Accepted: 09/09/2022] [Indexed: 02/01/2023]
Abstract
Colorectal cancer (CRC) develops mainly from colorectal advanced adenomas (AA), which are considered precancerous lesions. Novel early diagnostic biomarkers are urgently needed to distinguish CRC and AA from healthy control (HC). Alternative glycosylation of serum IgG has been shown to be closely associated with CRC. We aimed to explore the potential of IgG N-glycan as biomarkers in the early differential diagnosis of CRC. The study population was strictly matched to the exclusion criteria process. Serum IgG N-glycan profiles were analyzed by a robust and reliable relative quantitative method based on ultra-performance liquid chromatography (UPLC). Relative quantification and classification performance of IgG N-glycans were evaluated by Mann-Whitney U tests and ROC curve based on directly detected and derived glycan traits, respectively. Six and 14 directly detected glycan traits were significantly changed in AA and CRC, respectively, compared with HC. GP1 and GP3 were able to accurately distinguish AA from HC for early precancerous lesions screening. GP4 and GP14 provided a high value in discriminating CRC from HC. A novel combined index named GlycoF, including GP1, GP3, GP4, GP14 and CEA was developed to provide a potential early diagnostic biomarker in discriminating simultaneously AA (AUC = 0.847) and CRC (AUC = 0.844) from HC. GlycoF also demonstrated a superior CRC detection rate across CRC all stages and conspicuous prediction ability of risk of relapse. Serum IgG N-glycans analysis provided powerful early screening biomarkers that can efficiently differentiate CRC and AA from HC.
Collapse
Affiliation(s)
- Yong Gu
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Bensong Duan
- Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jichen Sha
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Rongrong Zhang
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Jiteng Fan
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Xiaoyan Xu
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Huijuan Zhao
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Xiaoyun Niu
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Zhi Geng
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Jianxin Gu
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Ben Huang
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shifang Ren
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| |
Collapse
|
|
13
|
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.
Collapse
Affiliation(s)
| | | | | | | | - Andrea Loza
- Endoscopias/Digestivo, Hospital Santos Reyes
| | | |
Collapse
|
|
14
|
Bosch S, Acharjee A, Quraishi MN, Bijnsdorp IV, Rojas P, Bakkali A, Jansen EEW, Stokkers P, Kuijvenhoven J, Pham TV, Beggs AD, Jimenez CR, Struys EA, Gkoutos GV, de Meij TGJ, de Boer NKH. Integration of stool microbiota, proteome and amino acid profiles to discriminate patients with adenomas and colorectal cancer. Gut Microbes 2022; 14:2139979. [PMID: 36369736 PMCID: PMC9662191 DOI: 10.1080/19490976.2022.2139979] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Screening for colorectal cancer (CRC) reduces its mortality but has limited sensitivity and specificity. Aims We aimed to explore potential biomarker panels for CRC and adenoma detection and to gain insight into the interaction between gut microbiota and human metabolism in the presence of these lesions. METHODS This multicenter case-control cohort was performed between February 2016 and November 2019. Consecutive patients ≥18 years with a scheduled colonoscopy were asked to participate and divided into three age, gender, body-mass index and smoking status-matched subgroups: CRC (n = 12), adenomas (n = 21) and controls (n = 20). Participants collected fecal samples prior to bowel preparation on which proteome (LC-MS/MS), microbiota (16S rRNA profiling) and amino acid (HPLC) composition were assessed. Best predictive markers were combined to create diagnostic biomarker panels. Pearson correlation-based analysis on selected markers was performed to create networks of all platforms. RESULTS Combining omics platforms provided new panels which outperformed hemoglobin in this cohort, currently used for screening (AUC 0.98, 0.95 and 0.87 for CRC vs controls, adenoma vs controls and CRC vs adenoma, respectively). Integration of data sets revealed markers associated with increased blood excretion, stress- and inflammatory responses and pointed toward downregulation of epithelial integrity. CONCLUSIONS Integrating fecal microbiota, proteome and amino acids platforms provides for new biomarker panels that may improve noninvasive screening for adenomas and CRC, and may subsequently lead to lower incidence and mortality of colon cancer.
Collapse
Affiliation(s)
- Sofie Bosch
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Endocrinology Metabolism Institute, Amsterdam University Medical Centre, VU University Amsterdam, Amsterdam, The Netherlands,CONTACT Sofie Bosch Department of Gastroenterology and Hepatology, Amsterdam UMC, VU University Medical Center, De Boelelaan 1118, Amsterdam1081HZ, The Netherlands
| | - Animesh Acharjee
- College of Medical and Dental Sciences, Institute of Cancer and Genomic Sciences, Center for Computational Biology, University of Birmingham, Birmingham, UK,Institute of Translational Medicine, University Hospitals Birmingham NHS, Foundation Trust, UK,NIHR Surgical Reconstruction and Microbiology Research Center, University Hospital Birmingham, Birmingham, UK
| | - Mohammed Nabil Quraishi
- Department of Gastroenterology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK,Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK,Microbiome Treatment Center, University of Birmingham Microbiome Treatment Center, University of Birmingham, UK,Center for Liver and Gastroenterology Research, NIHR Birmingham Biomedical Research Center, University of Birmingham, Birmingham, UK
| | - Irene V Bijnsdorp
- Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands,Department of Urology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Patricia Rojas
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Abdellatif Bakkali
- Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
| | - Erwin EW Jansen
- Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
| | - Pieter Stokkers
- Department of Gastroenterology and Hepatology, OLVG West, Amsterdam, The Netherlands
| | - Johan Kuijvenhoven
- Spaarne Gasthuis, Department of Gastroenterology and Hepatology, Hoofddorp and Haarlem, The Netherlands
| | - Thang V Pham
- Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | - Andrew D Beggs
- Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
| | - Connie R Jimenez
- Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | - Eduard A Struys
- Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
| | - Georgios V Gkoutos
- College of Medical and Dental Sciences, Institute of Cancer and Genomic Sciences, Center for Computational Biology, University of Birmingham, Birmingham, UK,Institute of Translational Medicine, University Hospitals Birmingham NHS, Foundation Trust, UK,NIHR Surgical Reconstruction and Microbiology Research Center, University Hospital Birmingham, Birmingham, UK,Microbiome Treatment Center, MRC Health Data Research UK (HDR UK), Birmingham, UK,Microbiome Treatment Center, NIHR Experimental Cancer Medicine Center, Birmingham, UK,Microbiome Treatment Center, NIHR Biomedical Research Center, University Hospital Birmingham, Birmingham, UK
| | - Tim GJ de Meij
- Department of Paediatric Gastroenterology, AG&M Research Institute, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
| | - Nanne KH de Boer
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Endocrinology Metabolism Institute, Amsterdam University Medical Centre, VU University Amsterdam, Amsterdam, The Netherlands
| |
Collapse
|
|
15
|
van der Vlugt M, Carvalho B, Fliers J, Montazeri N, Rausch C, Grobbee EJ, Engeland MV, Spaander MCW, Meijer GA, Dekker E. Missed colorectal cancers in a fecal immunochemical test-based screening program: Molecular profiling of interval carcinomas. World J Gastrointest Oncol 2022; 14:2195-2207. [PMID: 36438700 PMCID: PMC9694267 DOI: 10.4251/wjgo.v14.i11.2195] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 09/06/2022] [Accepted: 10/03/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND For optimizing fecal immunochemical test (FIT)-based screening programs, reducing the rate of missed colorectal cancers (CRCs) by FIT (FIT-interval CRCs) is an important aspect. Knowledge of the molecular make-up of these missed lesions could facilitate more accurate detection of all (precursor) lesions.
AIM To compare the molecular make-up of FIT-interval CRCs to lesions that are detected by FIT [screen-detected CRCs (SD-CRCs)].
METHODS FIT-interval CRCs observed in a Dutch pilot-program of FIT-based screening were compared to a control group of SD-CRCs in a 1:2 ratio, resulting in 27 FIT-interval CRC and 54 SD-CRCs. Molecular analyses included microsatellite instability (MSI), CpG island methylator phenotype (CIMP), DNA sequence mutations and copy number alterations (CNAs).
RESULTS Although no significant differences were reached, FIT-interval CRCs were more often CIMP positive and MSI positive (33% CIMP in FIT-interval CRCs vs 21% in SD-CRCs (P = 0.274); 19% MSI in FIT-interval CRCs vs 12% in SD-CRCs (P = 0.469)), and showed more often serrated pathway associated features such as BRAF (30% vs 12%, P = 0.090) and PTEN (15% vs 2.4%, P = 0.063) mutations. APC mutations, a classic feature of the adenoma-carcinoma-sequence, were more abundant in SD-CRCs (68% vs 40% in FIT-interval CRCs P = 0.035). Regarding CNAs differences between the two groups; FIT-interval CRCs less often showed gains at the regions 8p11.22-q24.3 (P = 0.009), and more often gains at 20p13-p12.1 (P = 0.039).
CONCLUSION Serrated pathway associated molecular features seem to be more common in FIT-interval CRCs, while classic adenoma carcinoma pathway associated molecular features seem to be more common in SD-CRCs. This indicates that proximal serrated lesions may be overrepresented among FIT-interval CRCs.
Collapse
Affiliation(s)
- Manon van der Vlugt
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam 1105 AZ, Netherlands
| | - Beatriz Carvalho
- Department of Pathology, Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands
| | - Joelle Fliers
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam 1105 AZ, Netherlands
| | - Nahid Montazeri
- Biostatistics Unit, Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam 1105 AZ, Netherlands
| | - Christian Rausch
- Department of Pathology, Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands
| | - Esmée J Grobbee
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam 3015 CN, Netherlands
| | - Manon van Engeland
- Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht 6202 AZ, Netherlands
| | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam 3015 CN, Netherlands
| | - Gerrit A Meijer
- Department of Pathology, Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam 1105 AZ, Netherlands
| |
Collapse
|
|
16
|
van Wifferen F, Greuter MJE, Lissenberg-Witte BI, Carvalho B, Meijer GA, Dekker E, Campari C, Garcia M, Rabeneck L, Lansdorp-Vogelaar I, Senore C, Coupé VMH, Segnan N, McCarthy S, Puricelli-Perin DM, Portillo I, Jahn B. Guidance for setting international standards on reporting longitudinal adherence to stool-based colorectal cancer screening. Prev Med 2022; 164:107187. [PMID: 35963311 DOI: 10.1016/j.ypmed.2022.107187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 06/01/2022] [Accepted: 08/05/2022] [Indexed: 11/26/2022]
Abstract
Longitudinal adherence to colorectal cancer (CRC) screening is reported using different summarizing measures, which hampers international comparison. We provide evidence to guide recommendations on which longitudinal adherence measure to report. Using adherence data over four stool-based CRC screening rounds in three countries, we calculated six summarizing adherence measures; adherence over all rounds, adherence per round, rescreening, full programme adherence (yes/no), regularity (never/inconsistent/consistent screenees) and number of times participated. For each measure, we calculated the accuracy in capturing the observed adherence patterns. Using the ASCCA model, we predicted screening effectiveness when using summarizing measures as model input versus the observed adherence patterns. Adherence over all rounds in the Italian, Spanish and Dutch cohorts was 64.9%, 42.8% and 61.5%, respectively, and the proportion of consistent screenees was 50.9%, 26.3% and 45.7%. Number of times participated and regularity were most accurate and resulted in similar model-predicted screening effectiveness as simulating the observed adherence patterns of Italy, Spain and the Netherlands (mortality reductions: 24.4%, 16.9% and 23.5%). Adherence over all rounds and adherence per round were least accurate. Screening effectiveness was overestimated when using adherence over all rounds (mortality reductions: 26.8%, 19.4% and 25.7%) and adherence per round (mortality reductions: 26.8%, 19.5% and 25.9%). To conclude, number of times participated and regularity were most accurate and resulted in similar model-predicted screening effectiveness as using the observed adherence patterns. However they require longitudinal data. To facilitate international comparison of CRC screening programme performance, consensus on an accurate adherence measure to report should be reached.
Collapse
Affiliation(s)
- Francine van Wifferen
- Department of Epidemiology and Data Science, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands.
| | - Marjolein J E Greuter
- Department of Epidemiology and Data Science, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands
| | - Birgit I Lissenberg-Witte
- Department of Epidemiology and Data Science, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands
| | - Beatriz Carvalho
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Gerrit A Meijer
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam UMC location University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands
| | - Cinzia Campari
- Screening Unit, Azienda USL-IRCCS di Reggio Emilia, Italy
| | - Montse Garcia
- Cancer Screening Unit, Prevention and Control Programme, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Linda Rabeneck
- Prevention & Cancer Control, Ontario Health (Cancer Care Ontario), University of Toronto, Canada
| | - Iris Lansdorp-Vogelaar
- Department of Public Health, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands
| | - Carlo Senore
- SSD Epidemiology, screening unit - CPO, University Hospital "Città della Salute e della Scienza", Turin, Italy
| | - Veerle M H Coupé
- Department of Epidemiology and Data Science, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands
| | | | - Nereo Segnan
- Centre for Cancer Prevention, CPO, Piedmonte, Turin, Italy
| | - Sharon McCarthy
- Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, USA
| | | | - Isabel Portillo
- Osakidetza Basque Health Service, Basque Country Colorectal Cancer Screening Programme, 48011 Bilbao, Spain; Biocruces Health Research Institute, Cancer Biomarker Area, 48903 Barakaldo, Spain
| | - Beate Jahn
- Department of Public Health, Health Services Research and Health Technology Assessment, Institute of Public Health, Medical Decision Making and Health Technology Assessment, UMIT-University for Health Sciences, Medical Informatics and Technology, Eduard-Wallnoefer Zentrum 1, A-6060 Hall in Tirol, Austria
| |
Collapse
|
|
17
|
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.
Collapse
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
| |
Collapse
|
|
18
|
Han T, Cong H, Yu B, Shen Y. Application of peptide biomarkers in life analysis based on liquid chromatography-mass spectrometry technology. Biofactors 2022; 48:725-743. [PMID: 35816279 DOI: 10.1002/biof.1875] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 06/18/2022] [Indexed: 12/11/2022]
Abstract
Biomedicine is developing rapidly in the 21st century. Among them, the qualitative and quantitative analysis of peptide biomarkers is of considerable importance for the diagnosis and therapy of diseases and the quality evaluation of drugs and food. The identification and quantitative analysis of peptides have been going on for decades. Traditionally, immunoassays or biological assays are generally used to quantify peptides in biological matrices. However, the selectivity and sensitivity of these methods cannot meet the requirements of the application. The separation and analysis technique of liquid chromatography-mass spectrometry (LC-MS) supplies a reliable alternative. In contrast to immunoassays, LC-MS methods are capable of providing the analytical prowess necessary to satisfy the demands of peptide biomarker research in the life sciences arena. This review article provides a historical account of the in-roads made by LC-MS technology for the detection of peptide biomarkers in the past 10 years, with the focus on the qualification/quantification developments and their applications.
Collapse
Affiliation(s)
- Tingting Han
- Institute of Biomedical Materials and Engineering, College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao, China
| | - Hailin Cong
- Institute of Biomedical Materials and Engineering, College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao, China
- State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao University, Qingdao, China
| | - Bing Yu
- Institute of Biomedical Materials and Engineering, College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao, China
- State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao University, Qingdao, China
| | - Youqing Shen
- Institute of Biomedical Materials and Engineering, College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao, China
- Center for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China
| |
Collapse
|
|
19
|
Kuwabara H, Katsumata K, Iwabuchi A, Udo R, Tago T, Kasahara K, Mazaki J, Enomoto M, Ishizaki T, Soya R, Kaneko M, Ota S, Enomoto A, Soga T, Tomita M, Sunamura M, Tsuchida A, Sugimoto M, Nagakawa Y. Salivary metabolomics with machine learning for colorectal cancer detection. Cancer Sci 2022; 113:3234-3243. [PMID: 35754317 PMCID: PMC9459332 DOI: 10.1111/cas.15472] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 06/07/2022] [Accepted: 06/15/2022] [Indexed: 11/29/2022] Open
Abstract
As the worldwide prevalence of colorectal cancer (CRC) increases, it is vital to reduce its morbidity and mortality through early detection. Saliva‐based tests are an ideal noninvasive tool for CRC detection. Here, we explored and validated salivary biomarkers to distinguish patients with CRC from those with adenoma (AD) and healthy controls (HC). Saliva samples were collected from patients with CRC, AD, and HC. Untargeted salivary hydrophilic metabolite profiling was conducted using capillary electrophoresis–mass spectrometry and liquid chromatography–mass spectrometry. An alternative decision tree (ADTree)‐based machine learning (ML) method was used to assess the discrimination abilities of the quantified metabolites. A total of 2602 unstimulated saliva samples were collected from subjects with CRC (n = 235), AD (n = 50), and HC (n = 2317). Data were randomly divided into training (n = 1301) and validation datasets (n = 1301). The clustering analysis showed a clear consistency of aberrant metabolites between the two groups. The ADTree model was optimized through cross‐validation (CV) using the training dataset, and the developed model was validated using the validation dataset. The model discriminating CRC + AD from HC showed area under the receiver‐operating characteristic curves (AUC) of 0.860 (95% confidence interval [CI]: 0.828‐0.891) for CV and 0.870 (95% CI: 0.837‐0.903) for the validation dataset. The other model discriminating CRC from AD + HC showed an AUC of 0.879 (95% CI: 0.851‐0.907) and 0.870 (95% CI: 0.838‐0.902), respectively. Salivary metabolomics combined with ML demonstrated high accuracy and versatility in detecting CRC.
Collapse
Affiliation(s)
- Hiroshi Kuwabara
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Kenji Katsumata
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Atsuhiro Iwabuchi
- Center for Health Surveillance and Preventive Medicine, Tokyo Medical University Hospital, Tokyo, Japan
| | - Ryutaro Udo
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Tomoya Tago
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Kenta Kasahara
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Junichi Mazaki
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Masanobu Enomoto
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Tetsuo Ishizaki
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Ryoko Soya
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Miku Kaneko
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
| | - Sana Ota
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
| | - Ayame Enomoto
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
| | - Tomoyoshi Soga
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
| | - Masaru Tomita
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
| | - Makoto Sunamura
- Digestive Surgery and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan
| | - Akihiko Tsuchida
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Masahiro Sugimoto
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan.,Research and Development Center for Minimally Invasive Therapies Health Promotion and Preemptive Medicine, Tokyo Medical University, Shinjuku, Tokyo, Japan
| | - Yuichi Nagakawa
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| |
Collapse
|
|
20
|
Grobbee EJ, Wisse PHA, Schreuders EH, van Roon A, van Dam L, Zauber AG, Lansdorp-Vogelaar I, Bramer W, Berhane S, Deeks JJ, Steyerberg EW, van Leerdam ME, Spaander MC, Kuipers EJ. Guaiac-based faecal occult blood tests versus faecal immunochemical tests for colorectal cancer screening in average-risk individuals. Cochrane Database Syst Rev 2022; 6:CD009276. [PMID: 35665911 PMCID: PMC9169237 DOI: 10.1002/14651858.cd009276.pub2] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Worldwide, many countries have adopted colorectal cancer (CRC) screening programmes, often based on faecal occult blood tests (FOBTs). CRC screening aims to detect advanced neoplasia (AN), which is defined as CRC or advanced adenomas. FOBTs fall into two categories based on detection technique and the detected blood component: qualitative guaiac-based FOBTs (gFOBTs) and faecal immunochemical tests (FITs), which can be qualitative and quantitative. Screening with gFOBTs reduces CRC-related mortality. OBJECTIVES To compare the diagnostic test accuracy of gFOBT and FIT screening for detecting advanced colorectal neoplasia in average-risk individuals. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, BIOSIS Citation Index, Science Citation Index Expanded, and Google Scholar. We searched the reference lists and PubMed-related articles of included studies to identify additional studies. SELECTION CRITERIA We included prospective and retrospective studies that provided the number of true positives, false positives, false negatives, and true negatives for gFOBTs, FITs, or both, with colonoscopy as reference standard. We excluded case-control studies. We included studies in which all participants underwent both index test and reference standard ("reference standard: all"), and studies in which only participants with a positive index test underwent the reference standard while participants with a negative test were followed for at least one year for development of interval carcinomas ("reference standard: positive"). The target population consisted of asymptomatic, average-risk individuals undergoing CRC screening. The target conditions were CRC and advanced neoplasia (advanced adenomas and CRC combined). DATA COLLECTION AND ANALYSIS Two review authors independently screened and selected studies for inclusion. In case of disagreement, a third review author made the final decision. We used the Rutter and Gatsonis hierarchical summary receiver operating characteristic model to explore differences between tests and identify potential sources of heterogeneity, and the bivariate hierarchical model to estimate sensitivity and specificity at common thresholds: 10 µg haemoglobin (Hb)/g faeces and 20 µg Hb/g faeces. We performed indirect comparisons of the accuracy of the two tests and direct comparisons when both index tests were evaluated in the same population. MAIN RESULTS We ran the initial search on 25 June 2019, which yielded 63 studies for inclusion. We ran a top-up search on 14 September 2021, which yielded one potentially eligible study, currently awaiting classification. We included a total of 33 "reference standard: all" published articles involving 104,640 participants. Six studies evaluated only gFOBTs, 23 studies evaluated only FITs, and four studies included both gFOBTs and FITs. The cut-off for positivity of FITs varied between 2.4 μg and 50 µg Hb/g faeces. For each Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 domain, we assessed risk of bias as high in less than 20% of studies. The summary curve showed that FITs had a higher discriminative ability than gFOBTs for AN (P < 0.001) and CRC (P = 0.004). For the detection of AN, the summary sensitivity of gFOBTs was 15% (95% confidence interval (CI) 12% to 20%), which was significantly lower than FITs at both 10 μg and 20 μg Hb/g cut-offs with summary sensitivities of 33% (95% CI 27% to 40%; P < 0.001) and 26% (95% CI 21% to 31%, P = 0.002), respectively. Results were simulated in a hypothetical cohort of 10,000 screening participants with 1% CRC prevalence and 10% AN prevalence. Out of 1000 participants with AN, gFOBTs missed 850, while FITs missed 670 (10 μg Hb/g cut-off) and 740 (20 μg Hb/g cut-off). No significant differences in summary specificity for AN detection were found between gFOBTs (94%; 95% CI 92% to 96%), and FITs at 10 μg Hb/g cut-off (93%; 95% CI 90% to 95%) and at 20 μg Hb/g cut-off (97%; 95% CI 95% to 98%). So, among 9000 participants without AN, 540 were offered (unnecessary) colonoscopy with gFOBTs compared to 630 (10 μg Hb/g) and 270 (20 μg Hb/g) with FITs. Similarly, for the detection of CRC, the summary sensitivity of gFOBTs, 39% (95% CI 25% to 55%), was significantly lower than FITs at 10 μg and 20 μg Hb/g cut-offs: 76% (95% CI 57% to 88%: P = 0.001) and 65% (95% CI 46% to 80%; P = 0.035), respectively. So, out of 100 participants with CRC, gFOBTs missed 61, and FITs missed 24 (10 μg Hb/g) and 35 (20 μg Hb/g). No significant differences in summary specificity for CRC were found between gFOBTs (94%; 95% CI 91% to 96%), and FITs at the 10 μg Hb/g cut-off (94%; 95% CI 87% to 97%) and 20 μg Hb/g cut-off (96%; 95% CI 91% to 98%). So, out of 9900 participants without CRC, 594 were offered (unnecessary) colonoscopy with gFOBTs versus 594 (10 μg Hb/g) and 396 (20 μg Hb/g) with FITs. In five studies that compared FITs and gFOBTs in the same population, FITs showed a higher discriminative ability for AN than gFOBTs (P = 0.003). We included a total of 30 "reference standard: positive" studies involving 3,664,934 participants. Of these, eight were gFOBT-only studies, 18 were FIT-only studies, and four studies combined both gFOBTs and FITs. The cut-off for positivity of FITs varied between 5 µg to 250 µg Hb/g faeces. For each QUADAS-2 domain, we assessed risk of bias as high in less than 20% of studies. The summary curve showed that FITs had a higher discriminative ability for detecting CRC than gFOBTs (P < 0.001). The summary sensitivity for CRC of gFOBTs, 59% (95% CI 55% to 64%), was significantly lower than FITs at the 10 μg Hb/g cut-off, 89% (95% CI 80% to 95%; P < 0.001) and the 20 μg Hb/g cut-off, 89% (95% CI 85% to 92%; P < 0.001). So, in the hypothetical cohort with 100 participants with CRC, gFOBTs missed 41, while FITs missed 11 (10 μg Hb/g) and 11 (20 μg Hb/g). The summary specificity of gFOBTs was 98% (95% CI 98% to 99%), which was higher than FITs at both 10 μg and 20 μg Hb/g cut-offs: 94% (95% CI 92% to 95%; P < 0.001) and 95% (95% CI 94% to 96%; P < 0.001), respectively. So, out of 9900 participants without CRC, 198 were offered (unnecessary) colonoscopy with gFOBTs compared to 594 (10 μg Hb/g) and 495 (20 μg Hb/g) with FITs. At a specificity of 90% and 95%, FITs had a higher sensitivity than gFOBTs. AUTHORS' CONCLUSIONS FITs are superior to gFOBTs in detecting AN and CRC in average-risk individuals. Specificity of both tests was similar in "reference standard: all" studies, whereas specificity was significantly higher for gFOBTs than FITs in "reference standard: positive" studies. However, at pre-specified specificities, the sensitivity of FITs was significantly higher than gFOBTs.
Collapse
Affiliation(s)
- Esmée J Grobbee
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Pieter HA Wisse
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Eline H Schreuders
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Aafke van Roon
- Department of Gastroenterology and Hepatology, Albert Schweitzer Hospital, Dordrecht, Netherlands
| | - Leonie van Dam
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Ann G Zauber
- Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, USA
| | - Iris Lansdorp-Vogelaar
- Department of Public Health, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Wichor Bramer
- Medical Library , Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Sarah Berhane
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
| | - Jonathan J Deeks
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
| | - Ewout W Steyerberg
- Department of Public Health, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Monique E van Leerdam
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Manon Cw Spaander
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Ernst J Kuipers
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands
| |
Collapse
|
|
21
|
Knudsen MD, Kvaerner AS, Botteri E, Holme Ø, Hjartåker A, Song M, Thiis-Evensen E, Randel KR, Hoff G, Berstad P. Lifestyle predictors for inconsistent participation to fecal based colorectal cancer screening. BMC Cancer 2022; 22:172. [PMID: 35168592 PMCID: PMC8848967 DOI: 10.1186/s12885-022-09287-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 02/03/2022] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Consistent participation in colorectal cancer (CRC) screening with repeated fecal immunochemical test (FIT) is important for the success of the screening program. We investigated whether lifestyle risk factors for CRC were related to inconsistent participation in up to four rounds of FIT-screening. METHOD We included data from 3,051 individuals who participated in up to four FIT-screening rounds and returned a lifestyle questionnaire. Using logistic regression analyses, we estimated associations between smoking habits, body mass index (BMI), physical activity, alcohol consumption, diet and a healthy lifestyle score (from least favorable 0 to most favorable 5), and inconsistent participation (i.e. not participating in all rounds of eligible FIT screening invitations). RESULTS Altogether 721 (24%) individuals were categorized as inconsistent participants Current smoking and BMI ≥30 kg/m2 were associated with inconsistent participation; odds ratios (ORs) and 95% confidence intervals (CIs) were 1.54 (1.21-2.95) and 1.54 (1.20-1.97), respectively. A significant trend towards inconsistent participation by a lower healthy lifestyle score was observed (p < 0.05). CONCLUSIONS Lifestyle behaviors were associated with inconsistent participation in FIT-screening. Initiatives aimed at increasing participation rates among those with the unhealthiest lifestyle have a potential to improve the efficiency of screening.
Collapse
Affiliation(s)
- Markus Dines Knudsen
- Section for Colorectal Cancer Screening, Cancer Registry of Norway, P.O. Box 5313, 0304, Majorstuen, Oslo, Norway.
- Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Norwegian PSC Research Center, Oslo University Hospital, P.O. Box 4950, 0424, Rikshospitalet, Nydalen, Oslo, Norway.
- Departments of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, 02115, Boston, MA, USA.
| | - Ane Sørlie Kvaerner
- Section for Colorectal Cancer Screening, Cancer Registry of Norway, P.O. Box 5313, 0304, Majorstuen, Oslo, Norway
| | - Edoardo Botteri
- Section for Colorectal Cancer Screening, Cancer Registry of Norway, P.O. Box 5313, 0304, Majorstuen, Oslo, Norway
- Department of Research, Cancer Registry of Norway, P.O. Box 5313, 0304, Majorstuen, Oslo, Norway
| | - Øyvind Holme
- Department of Medicine, Sørlandet Hospital Kristiansand, P.O. Box 416, 4604, Lundsiden, Kristiansand, Norway
- Department of Health Management and Health Economis, Institute of Health and Society, University of Oslo, P.O. Box 1089, 0317, Blindern, Oslo, Norway
| | - Anette Hjartåker
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1046, 0317, Blindern, Oslo, Norway
| | - Mingyang Song
- Departments of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, 02115, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, 02114, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, 02114, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, MA, Boston, USA
| | - Espen Thiis-Evensen
- Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Norwegian PSC Research Center, Oslo University Hospital, P.O. Box 4950, 0424, Rikshospitalet, Nydalen, Oslo, Norway
| | - Kristin Ranheim Randel
- Section for Colorectal Cancer Screening, Cancer Registry of Norway, P.O. Box 5313, 0304, Majorstuen, Oslo, Norway
| | - Geir Hoff
- Section for Colorectal Cancer Screening, Cancer Registry of Norway, P.O. Box 5313, 0304, Majorstuen, Oslo, Norway
- Department of Health Management and Health Economis, Institute of Health and Society, University of Oslo, P.O. Box 1089, 0317, Blindern, Oslo, Norway
- Department of Research and Development, Telemark Hospital Trust, Ulefossvegen 55, 3710, Skien, Norway
| | - Paula Berstad
- Section for Colorectal Cancer Screening, Cancer Registry of Norway, P.O. Box 5313, 0304, Majorstuen, Oslo, Norway
| |
Collapse
|
|
22
|
Perez NP, Baez YA, Stapleton SM, Muniappan A, Oseni TS, Goldstone RN, Chang DC. Racially Conscious Cancer Screening Guidelines: A Path Towards Culturally Competent Science. Ann Surg 2022; 275:259-270. [PMID: 33064394 DOI: 10.1097/sla.0000000000003983] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To review the racial composition of the study populations that the current USPSTF screening guidelines for lung, breast, and colorectal cancer are based on, and the effects of their application across non-white individuals. SUMMARY OF BACKGROUND DATA USPSTF guidelines commonly become the basis for establishing standards of care, yet providers are often unaware of the racial composition of the study populations they are based on. METHODS We accessed the USPSTF screening guidelines for lung, breast, and colorectal cancer via their website, and reviewed all referenced publications for randomized controlled trials (RCTs), focusing on the racial composition of their study populations. We then used PubMed to identify publications addressing the generalizability of such guidelines across non-white individuals. Lastly, we reviewed all guidelines published by non-USPSTF organizations to identify the availability of race-specific recommendations. RESULTS Most RCTs used as basis for the current USPSTF guidelines either did not report race, or enrolled cohorts that were not representative of the U.S. population. Several studies were identified demonstrating the broad application of such guidelines across non-white individuals can lead to underdiagnosis and higher levels of advanced disease. Nearly all guideline-issuing bodies fail to provide race-specific recommendations, despite often acknowledging increased disease burden among non-whites. CONCLUSION Concerted efforts to overcome limitations in the generalizability of RCTs are required to provide screening guidelines that are truly applicable to non-white populations. Broader policy changes to improve the pipeline for minority populations into science and medicine are needed to address the ongoing lack of diversity in these fields.
Collapse
Affiliation(s)
- Numa P Perez
- Massachusetts General Hospital, Department of Surgery, Boston, Massachusetts
- Massachusetts General Hospital, Healthcare Transformation Lab, Boston, Massachusetts
- Massachusetts General Hospital, Codman Center for Clinical Effectiveness in Surgery, Boston, Massachusetts
| | - Yefri A Baez
- Massachusetts General Hospital, Codman Center for Clinical Effectiveness in Surgery, Boston, Massachusetts
- Harvard Medical School, Boston, Massachusetts
| | - Sahael M Stapleton
- Massachusetts General Hospital, Department of Surgery, Boston, Massachusetts
- Massachusetts General Hospital, Codman Center for Clinical Effectiveness in Surgery, Boston, Massachusetts
| | - Ashok Muniappan
- Massachusetts General Hospital, Department of Surgery, Boston, Massachusetts
| | - Tawakalitu S Oseni
- Massachusetts General Hospital, Department of Surgery, Boston, Massachusetts
| | - Robert N Goldstone
- Massachusetts General Hospital, Department of Surgery, Boston, Massachusetts
| | - David C Chang
- Massachusetts General Hospital, Codman Center for Clinical Effectiveness in Surgery, Boston, Massachusetts
| |
Collapse
|
|
23
|
Predictive Modeling of Colonoscopic Findings in a Fecal Immunochemical Test-Based Colorectal Cancer Screening Program. Dig Dis Sci 2022; 67:2842-2848. [PMID: 34350518 PMCID: PMC9237000 DOI: 10.1007/s10620-021-07160-6] [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: 05/11/2021] [Accepted: 07/06/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND The fecal immunochemical test (FIT) is the primary modality used by the Los Angeles County Department of Health Services (LADHS) for colorectal cancer (CRC) screening in average-risk patients. Some patients referred for FIT-positive diagnostic colonoscopy have neither adenomas nor more advanced pathology. We aimed to identify predictors of false-positive FIT (FP-FIT) results in our largely disenfranchised, low socioeconomic status population. METHODS We conducted a retrospective study of 596 patients who underwent diagnostic colonoscopy following a positive screening FIT. Colonoscopies showing adenomas (or more advanced pathology) were considered positive. We employed multiple logistic and linear regression as well as machine learning models (MLMs) to identify clinical predictors of FP-FIT (primary outcome) and the presence of advanced adenomas (secondary outcome). RESULTS Overall, 268 patients (45.0%) had a FP-FIT. Female sex and hemorrhoids (odds ratios [ORs] 1.59 and 1.89, respectively) were associated with increased odds of FP-FIT and fewer advanced adenomas (β = - 0.658 and - 0.516, respectively). Conversely, increasing age and BMI (ORs 0.94 and 0.96, respectively) were associated with decreased odds of FP-FIT and a greater number of advanced adenomas (β = 0.073 and 0.041, respectively). MLMs predicted FP-FIT with high specificity (93.8%) and presence of advanced adenoma with high sensitivity (94.4%). CONCLUSION Increasing age and BMI are associated with lower odds of FP-FIT and greater number of advanced adenomas, while female sex and hemorrhoids are associated with higher odds of FP-FIT and fewer advanced adenomas. The presence of the aforementioned predictors may inform the decision to proceed with diagnostic colonoscopy in FIT-positive patients.
Collapse
|
|
24
|
Zhou RC, Wang PZ, Li YY, Zhang Y, Ma MJ, Meng FY, Liu C, Yang XY, Lv M, Zuo XL, Li YQ. Quality Improvement of Sample Collection Increases the Diagnostic Accuracy of Quantitative Fecal Immunochemical Test in Colorectal Cancer Screening: A Pilot Study. Front Med (Lausanne) 2021; 8:762560. [PMID: 34765625 PMCID: PMC8575757 DOI: 10.3389/fmed.2021.762560] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 09/22/2021] [Indexed: 01/02/2023] Open
Abstract
Objective: The diagnostic efficiency of the quantitative fecal immunochemical test (qFIT) has large variations in colorectal cancer (CRC) screening. We aimed to explore whether the practical sample collection operant training could improve the diagnostic accuracy of the qFIT in CRC screening. Methods: Moderate-/high-risk individuals aged 50–75 years old were invited to participate in a prospective observational study between July 2020 and March 2021. Participants took a qFIT sample without fecal sample collection operant training in advance and then completed another qFIT sample after the operant training. The primary outcome was the sensitivity and specificity of the qFITs for CRC and advanced colorectal neoplasia (ACRN). The secondary outcome was the difference in the area under the curves (AUCs) and the concentrations of the fecal hemoglobin (Hb) between the qFIT without and after the operant training. Results: Out of 913 patients, 81 (8.9%) patients had ACRN, including 25 (2.7%) patients with CRC. For CRC, the sensitivities of the qFIT without and after the operant training at 10 μg/g were 80.4 and 100.0%, respectively, and the specificities were 90.1 and 88.4%, respectively. For ACRN, the sensitivities were 49.4 and 69.1% and the specificities were 91.7 and 91.3%, respectively. The AUC of the qFIT after the operant training was significantly higher than that without the operant training for CRC (p = 0.027) and ACRN (p = 0.001). After the operant training, the concentration of the fecal Hb was significantly higher than that without the operant training (p = 0.009) for ACRN, but there was no significant difference for CRC (p = 0.367). Conclusion: Practical sample collection operant training improves the diagnostic accuracy of the qFIT, which increases the detection of the low concentrations of fecal Hb. Improving the quality of the sample collection could contribute to the diagnostic efficiency of the qFIT in CRC screening.
Collapse
Affiliation(s)
- Ru-Chen Zhou
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Shandong University, Jinan, China
| | - Pei-Zhu Wang
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Shandong University, Jinan, China
| | - Yue-Yue Li
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Shandong University, Jinan, China
| | - Yan Zhang
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Shandong University, Jinan, China
| | - Ming-Jun Ma
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Shandong University, Jinan, China
| | - Fan-Yi Meng
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Shandong University, Jinan, China
| | - Chao Liu
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Shandong University, Jinan, China
| | - Xiao-Yun Yang
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Shandong University, Jinan, China
| | - Ming Lv
- Clinical Epidemiology Unit, Qilu Hospital, Shandong University, Jinan, China
| | - Xiu-Li Zuo
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Shandong University, Jinan, China
| | - Yan-Qing Li
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Shandong University, Jinan, China
| |
Collapse
|
|
25
|
Chetroiu D, Pop CS, Filip PV, Beuran M. How and why do we screen for colorectal cancer? J Med Life 2021; 14:462-467. [PMID: 34621368 PMCID: PMC8485384 DOI: 10.25122/jml-2021-0192] [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: 06/24/2021] [Accepted: 08/03/2021] [Indexed: 12/24/2022] Open
Abstract
After almost 50 years of data analysis, screening for colorectal cancer has proven to be an effective tool in reducing colorectal cancer mortality. However, implementing the optimal strategy represents a challenge for many healthcare facilities around the world. There is much discussion regarding how screening should be done, the optimal tools that should be used, and the proper timing for screening procedures. Another essential step is to maintain the adherence of patients to screening programs. Also, the recommendation for lowering the age to initiate screening is in progress, as there is an increase in colorectal incidence in people born after 1970.
Collapse
Affiliation(s)
- Diana Chetroiu
- Department of Medical Oncology, Bucharest Emergency University Hospital, Bucharest, Romania.,Department of Internal Medicine and Gastroenterology, Bucharest Emergency University Hospital, Bucharest, Romania.,Department of Surgery, Bucharest Emergency Clinical Hospital, Bucharest, Romania
| | - Corina-Silvia Pop
- Department of Internal Medicine and Gastroenterology, Bucharest Emergency University Hospital, Bucharest, Romania
| | - Petruta Violeta Filip
- Department of Internal Medicine and Gastroenterology, Bucharest Emergency University Hospital, Bucharest, Romania
| | - Mircea Beuran
- Department of Surgery, Bucharest Emergency Clinical Hospital, Bucharest, Romania
| |
Collapse
|
|
26
|
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.
Collapse
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.)
| |
Collapse
|
|
27
|
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.
Collapse
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
| |
Collapse
|
|
28
|
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.
Collapse
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.)
| |
Collapse
|
|
29
|
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: 318] [Impact Index Per Article: 79.5] [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.
Collapse
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
| |
Collapse
|
|
30
|
Levy BT, Daly JM, Xu Y, Crockett SD, Hoffman RM, Dawson JD, Parang K, Shokar NK, Reuland DS, Zuckerman MJ, Levin A. Comparative effectiveness of five fecal immunochemical tests using colonoscopy as the gold standard: study protocol. Contemp Clin Trials 2021; 106:106430. [PMID: 33974994 DOI: 10.1016/j.cct.2021.106430] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 04/26/2021] [Accepted: 05/04/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND There are nearly 50,000 colorectal cancer (CRC) deaths in the United States each year. CRC is curable if detected in its early stages. Fecal immunochemical tests (FITs) can detect precursor lesions and many can be analyzed at the point-of-care (POC) in physician offices. However, there are few data to guide test selection. Broader use of FITs could make CRC screening more accessible, especially in resource-poor settings. METHODS A total of 3600 racially and ethnically diverse individuals aged 50 to 85 years having either a screening or surveillance colonoscopy will be recruited. Each participant will complete five FITs on a single stool sample. Test characteristics for each FIT for advanced colorectal neoplasia (ACN) will be calculated using colonoscopy as the gold standard. RESULTS We have complete data from a total of 2990 individuals. Thirty percent are Latino and 5.3% are black/African American. We will present full results once the study is completed. CONCLUSIONS Our focus in this study is how well FITs detect ACN, using colonoscopy as the gold standard. Four of the five FITs being used are POC tests. Although FITs have been shown to have acceptable performance, there is little data to guide which ones have the best test characteristics and colonoscopy is the main CRC screening test used in the United States. Use of FITs will allow broader segments of the population to access CRC screening because these tests require no preparation, are inexpensive, and can be collected in the privacy of one's home. Increasing CRC screening uptake will reduce the burden of advanced adenomas and colorectal cancer.
Collapse
Affiliation(s)
- Barcey T Levy
- Department of Family Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, United States of America; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States of America.
| | - Jeanette M Daly
- Department of Family Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America
| | - Yinghui Xu
- Department of Family Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America
| | - Seth D Crockett
- Department of Gastroenterology and Hepatology, North Carolina School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America
| | - Richard M Hoffman
- Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States of America; Department of Gastroenterology and Hepatology, North Carolina School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America
| | - Jeffrey D Dawson
- Department of Biostatistics and Dean's Office, College of Public Health, University of Iowa, Iowa City, IA, United States of America
| | - Kim Parang
- Department of Family Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America
| | - Navkiran K Shokar
- Department of Family and Community Medicine, Texas Tech University Health Sciences Center, El Paso, TX, United States of America
| | - Daniel S Reuland
- Department of Medicine, Division of General Medicine and Clinical Epidemiology, University of North Carolina School of Medicine, Chapel Hill, NC, United States of America
| | - Marc J Zuckerman
- Division of Gastroenterology, Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, United States of America
| | - Avraham Levin
- Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America
| |
Collapse
|
|
31
|
Chehab H, BouDaher H, Mokahal AE, ElHaddad A, Rimmani H, Hamadeh G, Tawil A, Sharara AI. Positive predictive value of fecal immunochemical test for high-risk colonic adenomas and carcinoma: A health maintenance organization cohort screening study in Lebanon. Arab J Gastroenterol 2021; 22:174-176. [PMID: 33965367 DOI: 10.1016/j.ajg.2021.04.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 02/01/2021] [Accepted: 04/08/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND STUDY AIMS Fecal Immunochemical Test (FIT) is one of the leading modalities for colorectal cancer screening. Studies show that FIT is highly sensitive for the detection of colorectal cancer (CRC) but not similarly accurate for detection of pre-cancerous advanced adenomas (AA). We studied the performance metrics of FIT for the detection of CRC and AA in ahealth maintenance organization (HMO) cohort screening program. PATIENTS AND METHODS Retrospective cohort study of asymptomatic persons of screening age belonging to a HMO. Endoscopy and pathology reports of those who tested positive were used to calculate the positive predictive value (PPV) of FIT, and characterize endoscopic findings on colonoscopy. RESULTS Between 1995 and 2017, 3000 persons had screening fecal occult testing as part of their Employee Health Care plan. Of those, 150 had a positive qualitative FIT (cutoff 10 µg hemoglobin/g feces). All underwentcolonoscopy, and median time to colonoscopy was 27 days. 4 (2.6%) had carcinoma(2 stage IIIA and 2 stage IIIB), 106 (70.6%) had adenomas of which 40 (26.6% of the total cohort) had advanced adenomas (≥1 cm, villous features, or high-grade dysplasia) giving a PPV for AA and carcinoma of 29% and 3% respectively. When stratified by age, the PPV of AA; carcinoma was [50-59 (21.7%; 0.0%)], [60-69 (14.6%; 4.2%)], [70-79 (42.6%; 2.1%)], [80-89 (33.3%; 11.1%)]. CONCLUSION The performance characteristics of FIT testing are acceptable for population screening in resource-limited settings. The resultsof this study are helpful when discussing expectations prior to colonoscopy in people with positive FIT.
Collapse
Affiliation(s)
- Hamed Chehab
- Division of Gastroenterology, American University of Beirut Medical Center, P.O. Box 11-0236/16-B, Beirut, Lebanon
| | - Halim BouDaher
- Division of Gastroenterology, American University of Beirut Medical Center, P.O. Box 11-0236/16-B, Beirut, Lebanon
| | - Ali El Mokahal
- Division of Gastroenterology, American University of Beirut Medical Center, P.O. Box 11-0236/16-B, Beirut, Lebanon
| | - Aline ElHaddad
- Division of Gastroenterology, American University of Beirut Medical Center, P.O. Box 11-0236/16-B, Beirut, Lebanon
| | - Hussein Rimmani
- Division of Gastroenterology, American University of Beirut Medical Center, P.O. Box 11-0236/16-B, Beirut, Lebanon
| | - Ghassan Hamadeh
- Department of Family Medicine, American University of Beirut Medical Center, PO Box: 11-0236, Riad El Sol, 1107 2020 Beirut, Lebanon
| | - Ayman Tawil
- Department of Pathology & Laboratory Medicine, American University of Beirut Medical Center, PO Box 11-0236, Riad El Solh 11072020, Beirut, Lebanon
| | - Ala I Sharara
- Division of Gastroenterology, American University of Beirut Medical Center, P.O. Box 11-0236/16-B, Beirut, Lebanon.
| |
Collapse
|
|
32
|
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.
Collapse
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
| |
Collapse
|
|
33
|
Benamouzig R, Barré S, Saurin JC, Leleu H, Vimont A, Taleb S, De Bels F. Cost-effectiveness analysis of alternative colorectal cancer screening strategies in high-risk individuals. Therap Adv Gastroenterol 2021; 14:17562848211002359. [PMID: 33953799 PMCID: PMC8042553 DOI: 10.1177/17562848211002359] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 02/15/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND AND AIMS Current guidelines recommend colonoscopy every 3-5 years for colorectal cancer (CRC) screening of individuals with a familial history of CRC. The objective of this study was to compare the cost effectiveness of screening alternatives in this population. METHODS Eight screening strategies were compared with no screening: fecal immunochemical test (FIT), Stool DNA and blood-based screening every 2 years, colonoscopy, computed tomography colonography, colon capsules, and sigmoidoscopy every 5 years, and colonoscopy at 45 years followed, if negative, by FIT every 2 years. Screening test and procedures performance were obtained from the literature. A microsimulation model reproducing the natural history of CRC was used to estimate the cost (€2018) and effectiveness [quality-adjusted life-years (QALYs)] of each strategy. A lifetime horizon was used. Costs and effectiveness were discounted at 3.5% annually. RESULTS Compared with no screening, colonoscopy and sigmoidoscopy at a 30% uptake were the most effective strategy (46.3 and 43.9 QALY/1000). FIT at a 30 µg/g threshold with 30% uptake was only half as effective (25.7 QALY). Colonoscopy was associated with a cost of €484,000 per 1000 individuals whereas sigmoidoscopy and FIT were associated with much lower costs (€123,610 and €66,860). Incremental cost-effectiveness rate for FIT and sigmoidoscopy were €2600/QALY (versus no screening) and €3100/QALY (versus FIT), respectively, whereas it was €150,000/QALY for colonoscopy (versus sigmoidoscopy). With a lower threshold (10 µg/g) and a higher uptake of 45%, FIT was more effective and less costly than colonoscopy at a 30% uptake and was associated with an incremental cost-effectiveness ratio (ICER) of €4240/QALY versus no screening. CONCLUSION At 30% uptake, current screening is the most effective screening strategy for high-risk individuals but is associated with a high ICER. Sigmoidoscopy and FIT at lower thresholds (10 µg/g) and a higher uptake should be given consideration as cost-effective alternatives. PLAIN LANGUAGE SUMMARY Cost-effectiveness analysis of colorectal cancer screening strategies in high-risk individuals Fecal occult blood testing with an immunochemical test (FIT) is generally considered as the most cost-effective alternative in colorectal cancer screening programs for average risk individuals without family history.Current screening guidelines for high-risk individuals with familial history recommend colonoscopy every 3-5 years.Colonoscopy every 3-5 years for individuals with familial history is the most effective strategy but is associated with a high incremental cost-effectiveness ratio.Compared with colonoscopy, if screening based on FIT is associated with a higher participation rate, it can achieve a similar effectiveness at a lower cost.
Collapse
Affiliation(s)
- Robert Benamouzig
- Department of Gastroenterology, Hôpital Avicenne (AP-HP), Bobigny, France
| | | | - Jean-Christophe Saurin
- Department of Endoscopy and Gastroenterology, Pavillon L, Edouard Herriot Hospital (Hospices Civils de Lyon), Lyon, France
| | - Henri Leleu
- Public Health Expertise, 157 rue du faubourg saint-Antoine, Paris, 75011, France
| | | | | | | |
Collapse
|
|
34
|
PPV and Detection Rate of mt-sDNA Testing, FIT, and CT Colonography for Advanced Neoplasia: A Hierarchic Bayesian Meta-Analysis of the Noninvasive Colorectal Screening Tests. AJR Am J Roentgenol 2021; 217:817-830. [PMID: 33703913 DOI: 10.2214/ajr.20.25416] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND. Noninvasive tests for colorectal cancer (CRC) screening and prevention limit the need for invasive colonoscopy to follow up positive test results. However, the relative performance characteristics of available noninvasive tests have not yet been adequately compared. OBJECTIVE. We performed a systematic review and meta-analysis to compare the diagnostic performance of the available noninvasive CRC screening tests, including multitarget stool DNA (mt-sDNA) testing, fecal immunochemical testing (FIT), and CT colonography (CTC), with an emphasis on comparison of PPV and detection rate (DR) for advanced neoplasia (AN; encompassing cases of advanced adenomas and CRC). EVIDENCE ACQUISITION. After systematic searches of MEDLINE and Google Scholar databases, 10 mt-sDNA, 27 CTC, and 88 FIT published screening studies involving 25,132, 33,493, and 2,355,958 asymptomatic adults, respectively, were included. Meta-analysis with hierarchic Bayesian modeling was conducted in accordance with Cochrane Collaboration and PRISMA guidelines to determine test positivity rates (TPRs) leading to optical colonoscopy, as well as PPVs and DRs for both AN and CRC. Different positivity thresholds were considered for FIT and CTC. EVIDENCE SYNTHESIS. Point estimates (with 95% credible intervals) from pooled Bayesian meta-analysis combining all thresholds for FIT and stratifying CTC results by a polyp size threshold of 6 mm or larger (CTC6) and 10 mm or larger (CTC10) were calculated. TPR was 13.5% (10.9-16.6%) for mt-sDNA testing, 6.4% (5.8-7.2%) for FIT, 13.4% (11.4-15.6%) for CTC6, and 6.6% (5.2-7.7%) for CTC10. AN PPV was 26.9% (95% credible interval, 21.8-33.2%) for mt-sDNA testing, 31.8% (29.3-34.5%) for FIT, 34.4% (27.2-41.0%) for CTC6, and 61.0% (54.0-70.0%) for CTC10. CRC PPV was 2.4% (1.5-3.9%) for mt-sDNA testing, 4.9% (4.3-5.3%) for FIT, 3.5% (2.5-4.8%) for CTC6, and 6.0% (4.3-8.0%) for CTC10. The DR for AN was 3.4% (95% credible interval, 2.5-4.8%) for mt-SDNA, 2.0% (1.8-2.3%) for FIT, 4.8% (4.0-6.5%) for CTC6, and 4.0% (3.0-4.6%) for CTC10. When FIT is restricted to a lower threshold (< 10 μg Hb/g feces), its performance profile is similar to that of mt-sDNA testing, although available data are limited. AN PPV odds ratios (relative to CTC10 as the reference) were 0.24 (95% credible interval, 0.17-0.33) for mt-sDNA testing, 0.30 (0.24-0.45) for FIT, and 0.33 (0.25-0.47) for CTC6. CONCLUSION. Among noninvasive CRC screening tests, CTC with a polyp size threshold of 10 mm or larger most effectively targets AN, preserving detection while also decreasing unnecessary colonoscopies compared with mt-sDNA testing and FIT. CLINICAL IMPACT. CTC performed with a polyp size threshold for colonoscopy referral set at 10 mm or larger represents the most effective and efficient noninvasive screening test for CRC prevention and detection.
Collapse
|
|
35
|
Yeh JH, Lin CW, Wang WL, Lee CT, Chen JC, Hsu CC, Wang JY. Positive Fecal Immunochemical Test Strongly Predicts Adenomas in Younger Adults With Fatty Liver and Metabolic Syndrome. Clin Transl Gastroenterol 2021; 12:e00305. [PMID: 33570858 PMCID: PMC7861879 DOI: 10.14309/ctg.0000000000000305] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Accepted: 12/18/2020] [Indexed: 01/08/2023] Open
Abstract
INTRODUCTION The incidence of early-onset colorectal cancer is increasing. This study explored the feasibility of fecal immunochemical test (FIT) and risk factors for predicting colorectal neoplasm in younger adults. METHODS This single-center study included 6,457 participants who underwent health examination from 2013 to 2016 including index colonoscopy (3,307 individuals aged 30-49 years as the younger adult group and 3,150 aged ≥50 years as the average-risk group). Primary outcomes were adenoma detection rate (ADR) and advanced ADR (AADR). Findings of younger participants were stratified by the results of FIT and clinical risk factors and were compared with those of the average-risk group. RESULTS Among participants aged 30-49 years, a positive FIT was associated with significantly higher ADR (28.5% vs 15.5, P < 0.001) and AADR (14.5% vs 3.7%, P < 0.001) than a negative FIT. Moreover, a positive FIT was associated with higher AADR in younger participants than in average-risk counterparts (14.5% vs 9.8%, P = 0.028). Although no single risk factor predicted FIT positivity in younger participants, nonalcoholic fatty liver disease was independently associated with higher ADR (odds ratio = 2.60, 95% confidence interval = 1.27-5.34, P = 0.001), and metabolic syndrome was independently predictive of higher AADR in younger participants than in average-risk participants (odds ratio = 3.46, 95% confidence interval = 1.66-7.21, P = 0.001). DISCUSSION A positive FIT in people aged 30-49 years implies a higher risk of colorectal neoplasm, particularly among patients with nonalcoholic fatty liver disease and metabolic syndrome.
Collapse
Affiliation(s)
- Jen-Hao Yeh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Dachang Hospital, Kaohsiung, Taiwan
- Department of Medical Technology, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Dachang Hospital, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Wen-Lun Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Ching-Tai Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Jen-Chieh Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Dachang Hospital, Kaohsiung, Taiwan
- Department of Health Examination, E-DA Hospital, Kaohsiung, Taiwan
| | - Chia-Chang Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan
- Department of Health Examination, E-DA Hospital, Kaohsiung, Taiwan
| | - Jaw-Yuan Wang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| |
Collapse
|
|
36
|
Njor SH, Andersen B, Friis-Hansen L, de Haas N, Linnemann D, Nørgaard H, Roikjaer O, Søndergaard B, Rasmussen M. The optimal cut-off value in fit-based colorectal cancer screening: An observational study. Cancer Med 2021; 10:1872-1879. [PMID: 33534955 PMCID: PMC7940214 DOI: 10.1002/cam4.3761] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 01/15/2021] [Accepted: 01/16/2021] [Indexed: 01/26/2023] Open
Abstract
Background Colorectal cancer (CRC) screening programs using fecal immunochemical test (FIT) have to choose a cut‐off value to decide which citizens to recall for colonoscopy. The evidence on the optimal cut‐off value is sparse and based on studies with a low number of cancer cases. Methods This observational study used data from the Danish Colorectal Cancer Screening Database. Sensitivity and specificity were estimated for various cut‐off values based on a large number of cancers. Traditionally optimal cut‐off values are found by weighting sensitivity and specificity equally. As this might result in too many unnecessary colonoscopies we also provide optimal cut‐off values for different weighting of sensitivity and specificity/number of needed colonoscopies to detect one cancer. Results Weighting sensitivity and specificity equally gives an optimal cut‐off value of 45 ng Hb/ml. This, however, means making 24 colonoscopies to detect one cancer. Weighting sensitivity lower and for example, aiming at making about 16 colonoscopies to detect one cancer, gives an optimal cut‐off value of 125 ng Hb/ml. Conclusions The optimal cut‐off value in an FIT population‐based screening program is 45 ng Hb/ml, when as traditionally sensitivity and specificity are weighted equally. If, however, 24 colonoscopies needed to detect one cancer is too huge a burden on the health care system and the participants, 80, 125, 175, and 350 ng Hb/ml are optimal cut‐off values when only 19/16/14/10 colonoscopies are accepted to find one cancer.
Collapse
Affiliation(s)
- Sisse Helle Njor
- Department of Public Health Programmes, Randers Regional Hospital, Randers, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Danish Colorectal Cancer Screening Database (DCCSD) Steering Committee, Aarhus, Denmark
| | - Berit Andersen
- Department of Public Health Programmes, Randers Regional Hospital, Randers, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Danish Colorectal Cancer Screening Database (DCCSD) Steering Committee, Aarhus, Denmark
| | - Lennart Friis-Hansen
- Danish Colorectal Cancer Screening Database (DCCSD) Steering Committee, Aarhus, Denmark.,Department of Clinical Biochemistry, Hilleroed Hospital, Hillerød, Denmark
| | - Niels de Haas
- Danish Colorectal Cancer Screening Database (DCCSD) Steering Committee, Aarhus, Denmark.,Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Dorte Linnemann
- Danish Colorectal Cancer Screening Database (DCCSD) Steering Committee, Aarhus, Denmark.,Department of Pathology, Herlev and Gentofte Hospital, Herlev, Denmark
| | - Henrik Nørgaard
- Danish Colorectal Cancer Screening Database (DCCSD) Steering Committee, Aarhus, Denmark.,Department of Radiology, Herlev Hospital, Herlev, Denmark
| | - Ole Roikjaer
- Danish Colorectal Cancer Screening Database (DCCSD) Steering Committee, Aarhus, Denmark.,Department of Surgery, Zealand University Hospital, Roskilde, Denmark
| | - Bo Søndergaard
- Danish Colorectal Cancer Screening Database (DCCSD) Steering Committee, Aarhus, Denmark.,Gastrounit, Medical Division, Hvidovre University Hospital, Hvidovre, Denmark
| | - Morten Rasmussen
- Danish Colorectal Cancer Screening Database (DCCSD) Steering Committee, Aarhus, Denmark.,Bispebjerg University Hospital, Copenhagen, Denmark
| |
Collapse
|
|
37
|
Gini A, Buskermolen M, Senore C, Anttila A, Novak Mlakar D, Veerus P, Csanádi M, Jansen EEL, Zielonke N, Heinävaara S, Széles G, Segnan N, de Koning HJ, Lansdorp-Vogelaar I. Development and Validation of Three Regional Microsimulation Models for Predicting Colorectal Cancer Screening Benefits in Europe. MDM Policy Pract 2021; 6:2381468320984974. [PMID: 33598546 PMCID: PMC7863172 DOI: 10.1177/2381468320984974] [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: 03/18/2020] [Accepted: 11/18/2020] [Indexed: 12/22/2022] Open
Abstract
Background. Validated microsimulation models have been shown to be useful tools in providing support for colorectal cancer (CRC) screening decisions. Aiming to assist European countries in reducing CRC mortality, we developed and validated three regional models for evaluating CRC screening in Europe. Methods. Microsimulation Screening Analysis–Colon (MISCAN-Colon) model versions for Italy, Slovenia, and Finland were quantified using data from different national institutions. These models were validated against the best available evidence for the effectiveness of screening from their region (when available): the Screening for COlon REctum (SCORE) trial and the Florentine fecal immunochemical test (FIT) screening study for Italy; the Norwegian Colorectal Cancer Prevention (NORCCAP) trial and the guaiac fecal occult blood test (gFOBT) Finnish population-based study for Finland. When published evidence was not available (Slovenia), the model was validated using cancer registry data. Results. Our three models reproduced age-specific CRC incidence rates and stage distributions in the prescreening period. Moreover, the Italian and Finnish models replicated CRC mortality reductions (reasonably) well against the best available evidence. CRC mortality reductions were predicted slightly larger than those observed (except for the Florentine FIT study), but consistently within the corresponding 95% confidence intervals. Conclusions. Our findings corroborate the MISCAN-Colon reliability in supporting decision making on CRC screening. Furthermore, our study provides the model structure for an additional tool (EU-TOPIA CRC evaluation tool: http://miscan.eu-topia.org) that aims to help policymakers and researchers monitoring or improving CRC screening in Europe.
Collapse
Affiliation(s)
- Andrea Gini
- Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Maaike Buskermolen
- Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Carlo Senore
- SC Epidemiology, Screening, Cancer Registry, Città della Salute e della Scienza University Hospital, CPO, Turin, Italy
| | | | | | - Piret Veerus
- National Institute for Health Development, Tallinn, Estonia
| | | | - Erik E L Jansen
- Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Nadine Zielonke
- Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | | | | | - Nereo Segnan
- SC Epidemiology, Screening, Cancer Registry, Città della Salute e della Scienza University Hospital, CPO, Turin, Italy
| | - Harry J de Koning
- Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Iris Lansdorp-Vogelaar
- Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| |
Collapse
|
|
38
|
Risk of colorectal adenomas and cancer in monoallelic carriers of MUTYH pathogenic variants: a single-centre experience. Int J Colorectal Dis 2021; 36:2199-2204. [PMID: 34244858 PMCID: PMC8426294 DOI: 10.1007/s00384-021-03983-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/16/2021] [Indexed: 02/04/2023]
Abstract
PURPOSE The carrier frequency of MUTYH pathogenic variants in the population may be as high as one in 45. Some studies have found an increased risk of colorectal cancer (CRC) in monoallelic carriers of MUTYH pathogenic variants, but the role of early surveillance colonoscopy is not conclusive. This study aimed to assess the outcomes of colonoscopy surveillance in MUTYH carriers. METHODS Patients, with a monoallelic pathogenic variant in MUTYH, found at cascade testing, were identified from the St Mark's Hospital Polyposis Registry database. Findings at surveillance colonoscopy were reviewed. RESULTS Two hundred and forty-nine carriers were identified, of whom 125 had undergone at least one surveillance colonoscopy. Twenty-eight patients (22%) developed at least one adenoma; all adenomas had low-grade dysplasia (LGD). The median age at first colonoscopy was 36 years (range 16-75 years). The median age at first adenoma detection was 43 years (range 22-75 years). The cumulative incidence of adenoma development by age 30, 40, 50, 60 and 70 years was 3.2%, 8.8%, 15.2%, 18.4% and 20.8%, respectively. No CRCs were observed. CONCLUSIONS Our cohort of monoallelic carriers of MUTYH pathogenic variants is a relatively younger group than adults entering population screening colonoscopy, but a high adenoma rate was not observed. No CRCs were detected, suggesting that current guidance that these individuals should be managed in the same way as the general population is reasonable.
Collapse
|
|
39
|
Barré S, Leleu H, Benamouzig R, Saurin JC, Vimont A, Taleb S, De Bels F. Cost-effectiveness analysis of alternative colon cancer screening strategies in the context of the French national screening program. Therap Adv Gastroenterol 2020; 13:1756284820953364. [PMID: 33014138 PMCID: PMC7509710 DOI: 10.1177/1756284820953364] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 07/31/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND A nationwide colorectal cancer (CRC) screening program was set up in France from 2009 for average-risk, asymptomatic people aged 50-74 years based on an immunochemical fecal occult blood test [faecal immunochemical test (FIT)] every 2 years, followed by colonoscopy if positive. The European standard recommends a participation rate of 45% for the program to be cost-effective, yet the latest published rate in France was 34%. The objective of this study was to compare the cost effectiveness of screening alternatives taking real-world participation rates into account. METHODS Eight screening strategies were compared, based either on a screening test (Guaiac or FIT testing, blood-based, stool DNA, computed tomography colonography, colon capsules, and sigmoidoscopy) followed by full colonoscopy if positive or direct colonoscopy. A microsimulation model was used to estimate the cost effectiveness associated with each strategy. RESULTS Compared with no screening, FIT was associated with a 14.0 quality-adjusted life year (QALY) increase of €50,520 per 1000 individuals, giving an incremental cost-effectiveness ratio (ICER) of €3600/QALY. Only stool DNA and blood-based testing were associated with a QALY increase compared with FIT, with stool DNA weakly dominated by blood-based testing, and the latter associated with an ICER of €154,600/QALY compared with FIT. All other strategies were dominated by FIT. CONCLUSION FIT every 2 years appears to be the most cost-effective CRC screening strategy when taking into account a real-world participation rate of 34%.
Collapse
Affiliation(s)
| | - Henri Leleu
- Public Health Expertise, 157 Rue du Faubourg Saint-Antoine, Paris, 75011, France
| | - R. Benamouzig
- Department of Gastroenterology, Hôpital Avicenne (AP-HP), Bobigny, France
| | - Jean-Christophe Saurin
- Department of Endoscopy and Gastroenterology, Pavillon L, Edouard Herriot Hospital (Hospices Civils de Lyon), Lyon, France
| | | | | | | |
Collapse
|
|
40
|
Mattar R, Marques SB, Minata MK, Silva-Etto JMKD, Sakai P, DE Moura EGH. DIAGNOSTIC ACCURACY OF ONE SAMPLE OR TWO SAMPLES QUANTITATIVE FECAL IMMUNOCHEMICAL TESTS FOR INTESTINAL NEOPLASIA DETECTION. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:316-322. [PMID: 32935747 DOI: 10.1590/s0004-2803.202000000-58] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 06/05/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Rectal bleeding is the most important symptom of intestinal neoplasia; thus, tests of occult blood detection in stools are widely used for pre neoplastic lesions and colorectal cancer (CRC) screening. OBJECTIVE Evaluate the accuracy of OC-Sensor quantitative test (Eiken Chemical, Tokyo, Japan) at cut-off 10 µg Hb/g feces (50 ng/mL) in a cohort of subjects that had to undergo diagnostic colonoscopy, and if more than one sample collected in consecutive days would improve the diagnostic accuracy of the test. METHODS Patients (mean age 56.3±9.7 years) that underwent colonoscopy prospectively randomly received one (1-sample FIT, FIT 1) or two (2-sample FIT, FIT 2) collection tubes. They collected the stool sample before starting colonoscopy preparation. Samples were analyzed by the OC-Auto Micro 80 (Eiken Chemical, Tokyo, Japan). The performance of FIT 1 and FIT 2 were compared to the colonoscopy findings. RESULTS Among 289 patients, CRC was diagnosed in 14 (4.8%), advanced adenoma in 37 (12.8%), early adenoma in 71 (24.6%) and no abnormalities in 141 (48.8%). For FIT 1, the sensitivity for CRC was 83.3% (95%CI 36.5-99.1%), for advanced adenoma was 24% (95%CI 10.1-45.5%), with specificity of 86.9% (95%CI 77.3-92.9%). For FIT 2, the sensitivity for CRC was 75% (95%CI 35.6-95.5%), for advanced adenoma was 50% (95%CI 22.3-77.7%), with specificity of 92.9% (95%CI 82.2-97.7%). The positive likelihood ratios were 1.8 (95%CI 0.7-4.4 for FIT 1) and 7.1 (95%CI 2.4-21.4 for FIT 2) for advanced adenoma, and 6.4 (95%CI 3.3-12.3, for FIT 1) and 10.7 (95%CI 3.8-29.8, for FIT 2) for CRC. The negative likelihood ratio were 0.9 (95%CI 0.7-1, for FIT 1) and 0.5 (95%CI 0.3-0.9, for FIT 2) for advanced adenoma, and 0.2 (0.03-1.1, for FIT 1) and 0.3 (0.08-0.9, for FIT 2) for CRC. The differences between FIT 1 and FIT 2 performances were not significant. However, the comparison of the levels of hemoglobin in feces of patients of FIT 1 and FIT 2 showed that the differences between no polyp group and advanced adenoma and CRC were significant. CONCLUSION The accuracy of OCR Sensor with 10 µg Hb/g feces cut-off was comparable to other reports and two-sample collection improved the detection rate of advanced adenoma, a pre neoplastic condition to prevent CRC incidence.
Collapse
Affiliation(s)
- Rejane Mattar
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Gastroenterologia e Hepatologia Clínica, São Paulo, SP, Brasil
| | - Sergio Barbosa Marques
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Endoscopia, São Paulo, SP, Brasil
| | - Maurício Kazuyoshi Minata
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Endoscopia, São Paulo, SP, Brasil
| | - Joyce Matie Kinoshita da Silva-Etto
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Gastroenterologia e Hepatologia Clínica, São Paulo, SP, Brasil
| | - Paulo Sakai
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Divisão de Endoscopia, São Paulo, SP, Brasil
| | | |
Collapse
|
|
41
|
Barré S, Leleu H, Vimont A, Kaufmanis A, Gendre I, Taleb S, De Bels F. [Estimated impact of the current colorectal screening program in France]. Rev Epidemiol Sante Publique 2020; 68:171-177. [PMID: 32417153 DOI: 10.1016/j.respe.2020.04.053] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 03/13/2020] [Accepted: 04/29/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Colorectal cancer is the third most common cancer and the second most deadly in France. A Cochrane meta-analysis has confirmed the benefits of colorectal cancer screening. A nationwide colorectal screening program was set up in France in 2009 for medium-risk, asymptomatic people aged 50 to 74 years. It has been based, since 2015, on the Fecal Immunochemical Test. The participation rate for 2016-2017 was 34%, which is lower than the European objectives. The objective of this study was to evaluate the impact of the program at the current participation rate and at rates of 45% and 65%. METHODS The epidemiological impact of the program was estimated from the results of an individual simulation model adapted from the Microsimulation Screening Analysis Colon model, calibrated and transposed to the French context. An initial analysis was conducted to estimate the individual impact of screening and a second for the entire eligible population, at various participation rates. RESULTS The test is associated with a lifetime reduction in the risk of colorectal cancer of 24% for men and 21% for women, and a reduction in the risk of death from colorectal cancer of 51% and 43% respectively. At the current level of participation, the program reduces incidence by 5% and mortality by 14% compared to no organized screening. The impact would be reduced by an additional 3% and 8% for participation rates of 45% and 65% respectively. Similarly, mortality would decrease by an additional 8% and 22%. CONCLUSION These results confirm that in a population at medium risk for colorectal cancer, the organised programme is an effective strategy for reducing its incidence. They also confirm that the achievement of European objectives remains a key issue for improving the effectiveness of organized screening. An evolution of immunological test delivery modalities could help to achieve these participation objectives.
Collapse
Affiliation(s)
- S Barré
- Institut national du cancer, Boulogne-Billancourt, France
| | - H Leleu
- Public Health Expertise, Paris, France
| | - A Vimont
- Public Health Expertise, Paris, France
| | - A Kaufmanis
- Centre de coordination des dépistages des cancers - région Île-de-France, Paris, France
| | - I Gendre
- Centre de coordination des dépistages des cancers - région Grand-Est, Vandœuvre-lès-Nancy, France
| | - S Taleb
- Institut national du cancer, Boulogne-Billancourt, France.
| | - F De Bels
- Institut national du cancer, Boulogne-Billancourt, France
| |
Collapse
|
|
42
|
Abstract
BACKGROUND Faecal occult blood testing is widely used in colorectal cancer screening. However, there is little empirical long-term evidence on the accumulation of false-positive test results over several screening rounds. We aimed to systematically explore and quantify the cumulative false-positive rate for various scenarios of colorectal cancer screening. METHODS Using a Markov analysis, we estimated the lifetime cumulative number of false-positive test results (cumFP) per 100 000 50-year-old persons. We varied the screening interval and the specificity of a single screening test and the starting age of screening. RESULTS For a test with a specificity of 98% used from 50 to 74 years, the cumFP at age 74 was 26 260 (1-year interval), 15 102 (2-year interval), and 10 819 (3-year interval), respectively. For a test with a specificity of, respectively, 95 and 92% used at a 2-year interval, the cumFP at age 74 was 2.2 times and 3.0 times higher as compared to a test with a specificity of 98%. The cumFP at age 74 was 18% lower for screening persons aged 54-74 years vs. 50-74 years. CONCLUSION Our findings quantitatively illustrate the large variation of the cumFP in colorectal cancer screening between screening strategies, which is relevant to informed decision making and adequate resource planning.
Collapse
Affiliation(s)
- Ulrike Haug
- Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology – BIPS,Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany
| | - Veerle M.H. Coupé
- Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| |
Collapse
|
|
43
|
Grobbee EJ, van der Vlugt M, van Vuuren AJ, Stroobants AK, Mallant-Hent RC, Lansdorp-Vogelaar I, Bossuyt PMM, Kuipers EJ, Dekker E, Spaander MCW. Diagnostic Yield of One-Time Colonoscopy vs One-Time Flexible Sigmoidoscopy vs Multiple Rounds of Mailed Fecal Immunohistochemical Tests in Colorectal Cancer Screening. Clin Gastroenterol Hepatol 2020; 18:667-675.e1. [PMID: 31419575 DOI: 10.1016/j.cgh.2019.08.015] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 07/23/2019] [Accepted: 08/02/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We compared the diagnostic yields of colonoscopy, flexible sigmoidoscopy, and fecal immunochemical tests (FITs) in colorectal cancer (CRC) screening. METHODS A total of 30,007 asymptomatic persons, 50-74 years old, were invited for CRC screening in the Netherlands. Participants were assigned to groups that received 4 rounds of FIT (mailed to 15,046 participants), once-only flexible sigmoidoscopy (n = 8407), or once-only colonoscopy (n = 6600). Patients with positive results from the FIT (≥10 μg Hb/g feces) were referred for colonoscopy. Patients who underwent flexible sigmoidoscopy were referred for colonoscopy if they had a polyp of ≥10 mm; adenoma with ≥25% villous histology or high-grade dysplasia; sessile serrated adenoma; ≥3 adenomas; ≥20 hyperplastic polyps; or invasive CRC. The primary outcome was number of advanced neoplasia detected (diagnostic yield) by each test. Secondary outcomes were number of colonoscopies needed to detect advanced neoplasia and number of interval CRCs found during each primary screening test. Patients with interval CRCs were found through linkage with Netherlands Cancer Registry. Advanced neoplasia were defined as CRC, adenomas ≥ 10 mm, adenomas with high-grade dysplasia, or adenomas with a villous component of at least 25%. RESULTS The cumulative participation rate was significantly higher for FIT screening (73%) than for flexible sigmoidoscopy (31%; P < .001) or colonoscopy (24%; P < .001). The percentage of colonoscopies among invitees was higher for colonoscopy (24%) compared to FIT (13%; P < .001) or flexible sigmoidoscopy (3%; P < .001). In the intention to screen analysis, the cumulative diagnostic yield of advanced neoplasia was higher with FIT screening (4.5%; 95% CI 4.2-4.9) than with colonoscopy (2.2%; 95% CI, 1.8-2.6) or flexible sigmoidoscopy (2.3%; 95% CI, 2.0-2.7). In the as-screened analysis, the cumulative yield of advanced neoplasia was higher for endoscopic screening with colonoscopy (9.1%; 95% CI, 7.7-10.7) or flexible sigmoidoscopy (7.4%; 95% CI, 6.5-8.5) than with the FIT (6.1%; 95% CI, 5.7-6.6). All 3 screening strategies detected a similar proportion of patients with CRC. Follow-up times differed for each test (median 8.3 years for FIT and flexible sigmoidoscopy and 5.8 years for colonoscopy). Proportions of patients that developed interval CRC were 0.13% for persons with a negative result from FIT, 0.09% for persons with a negative result from flexible sigmoidoscopy, and 0.01% for persons with a negative result from colonoscopy. CONCLUSIONS Mailed multiple-round FITs detect significantly more advanced neoplasia, on a population level, compared with once-only flexible sigmoidoscopy or colonoscopy screening. Significantly fewer colonoscopies are required by individuals screened by multiple FITs. Trialregister.nl numbers: first round, NTR1096; second round and additional invitees, NTR1512; fourth round, NTR5874; COCOS trial NTR1829.
Collapse
Affiliation(s)
- Esmée J Grobbee
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Manon van der Vlugt
- Department of Gastroenterology and Hepatology, Academic Medical Centre Amsterdam, Amsterdam, The Netherlands
| | - Anneke J van Vuuren
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - An K Stroobants
- Clinical Chemistry, Academic Medical Centre Amsterdam, Amsterdam, The Netherlands
| | | | - Iris Lansdorp-Vogelaar
- Department of Public Health, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Patrick M M Bossuyt
- Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, University of Amsterdam, The Netherlands
| | - Ernst J Kuipers
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Academic Medical Centre Amsterdam, Amsterdam, The Netherlands
| | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
| |
Collapse
|
|
44
|
Zhong GC, Sun WP, Wan L, Hu JJ, Hao FB. Efficacy and cost-effectiveness of fecal immunochemical test versus colonoscopy in colorectal cancer screening: a systematic review and meta-analysis. Gastrointest Endosc 2020; 91:684-697.e15. [PMID: 31790657 DOI: 10.1016/j.gie.2019.11.035] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Accepted: 11/19/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS The fecal immunochemical test (FIT) and colonoscopy are the most commonly used strategies for colorectal cancer (CRC) screening worldwide. We aimed to compare their efficacy and cost-effectiveness in CRC screening in an average-risk population. METHODS PubMed, Embase, and National Health Services Economic Evaluation Database were searched. Risk ratio (RR) was used to evaluate the differences in detection rates of colorectal neoplasia between FIT and colonoscopy groups. A random-effects model was used to pool RRs. Incremental cost-effectiveness ratios (ICERs) were calculated to evaluate the cost-effectiveness of FIT versus colonoscopy. RESULTS Six randomized controlled trials and 17 cost-effectiveness studies were included. The participation rate in the FIT group was higher than that in the colonoscopy group (41.6% vs 21.9%). In the intention-to-treat analysis, FIT had a detection rate of CRC comparable with colonoscopy (RR, .73; 95% confidence interval, .37-1.42) and lower detection rates of any adenoma and advanced adenoma than 1-time colonoscopy. Most included cost-effectiveness studies showed that annual (13/15) or biennial (5/6) FIT was cost-saving (ICER < $0) or very cost-effective ($0 < ICER ≤ $25000/quality-adjusted life-year) compared with colonoscopy every 10 years. CONCLUSIONS FIT may be similar to 1-time colonoscopy in the detection rate of CRC, although it has lower detection rates of any adenoma and advanced adenoma than 1-time colonoscopy. Furthermore, annual or biennial FIT appears to be very cost-effective or cost-saving compared with colonoscopy every 10 years. These findings indicate, at least partly, that FIT is noninferior to colonoscopy in CRC screening in an average-risk population. Our findings should be treated with caution and need to be further confirmed.
Collapse
Affiliation(s)
- Guo-Chao Zhong
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wei-Ping Sun
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lun Wan
- Department of Hepatobiliary Surgery, the People's Hospital of Dazu district, Chongqing, China
| | - Jie-Jun Hu
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Fa-Bao Hao
- Pediatric Surgery Center, Qingdao Women and Children's Hospital, Qingdao University, Qingdao, Shandong, China
| |
Collapse
|
|
45
|
Abstract
OBJECTIVES Specific microRNA (miRNA) signatures in biological fluids can facilitate earlier detection of the tumors being then minimally invasive diagnostic biomarkers. Circulating miRNAs have also emerged as promising diagnostic biomarkers for colorectal cancer (CRC) screening. In this study, we investigated the performance of a specific signature of miRNA in plasma samples to design a robust predictive model that can distinguish healthy individuals from those with CRC or advanced adenomas (AA) diseases. METHODS Case control study of 297 patients from 8 Spanish centers including 100 healthy individuals, 101 diagnosed with AA, and 96 CRC cases. Quantitative real-time reverse transcription was used to quantify a signature of miRNA (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) in plasma samples. Binary classifiers (Support Vector Machine [SVM] linear, SVM radial, and SVM polynomial) were built for the best predictive model. RESULTS Area under receiving operating characteristic curve of 0.92 (95% confidence interval 0.871-0.962) was obtained retrieving a model with a sensitivity of 0.85 and specificity of 0.90, positive predictive value of 0.94, and negative predictive value of 0.76 when advanced neoplasms (CRC and AA) were compared with healthy individuals. CONCLUSIONS We identified and validated a signature of 6 miRNAs (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) as predictors that can differentiate significantly patients with CRC and AA from those who are healthy. However, large-scale validation studies in asymptomatic screening participants should be conducted.
Collapse
|
|
46
|
Ternes D, Karta J, Tsenkova M, Wilmes P, Haan S, Letellier E. Microbiome in Colorectal Cancer: How to Get from Meta-omics to Mechanism? Trends Microbiol 2020; 28:401-423. [PMID: 32298617 DOI: 10.1016/j.tim.2020.01.001] [Citation(s) in RCA: 136] [Impact Index Per Article: 27.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 12/20/2019] [Accepted: 01/10/2020] [Indexed: 02/07/2023]
Abstract
Mounting evidence from metagenomic analyses suggests that a state of pathological microbial imbalance or dysbiosis is prevalent in the gut of patients with colorectal cancer. Several bacterial taxa have been identified of which representative isolate cultures interact with human cancer cells in vitro and trigger disease pathways in animal models. However, how the complex interrelationships in dysbiotic communities may be involved in cancer pathogenesis remains a crucial question. Here, we provide a survey of current knowledge of the gut microbiome in colorectal cancer. Moving beyond observational studies, we outline new experimental approaches for gaining ecosystem-level mechanistic understanding of the gut microbiome's role in cancer pathogenesis.
Collapse
Affiliation(s)
- Dominik Ternes
- Molecular Disease Mechanisms Group, Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Jessica Karta
- Molecular Disease Mechanisms Group, Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Mina Tsenkova
- Molecular Disease Mechanisms Group, Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Paul Wilmes
- Eco-Systems Biology group, Luxembourg Center for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Serge Haan
- Molecular Disease Mechanisms Group, Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Elisabeth Letellier
- Molecular Disease Mechanisms Group, Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
| |
Collapse
|
|
47
|
Hasegawa R, Yashima K, Ikebuchi Y, Sasaki S, Yoshida A, Kawaguchi K, Isomoto H. Characteristics of Advanced Colorectal Cancer Detected by Fecal Immunochemical Test Screening in Participants with a Negative Result the Previous Year. Yonago Acta Med 2020; 63:63-69. [PMID: 32158335 PMCID: PMC7028528 DOI: 10.33160/yam.2020.02.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 01/24/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND There is sufficient evidence to show the mortality reduction effect of colorectal cancer (CRC) screening programs using the fecal occult blood test (FOBT). However, we see cases that are found to be advanced CRC despite yearly FOBT screening. METHODS The aim of this study was to investigate the characteristics of advanced CRC detected by a fecal immunochemical test (FIT) screening program in participants with a negative screening result the previous year, which we call "Negative advanced CRC". A total of 109,639 participants (10.0% required colonoscopy, of whom 76.9% received one) underwent a CRC screening program using a FIT from fiscal 2009 to 2017. Negative advanced CRC was compared with advanced CRC (First advanced CRC) found at the first visit in a person who had not had a FIT screening history for more than 3 years. In addition, we compared the characteristics of Negative advanced CRC with those of interval cancer: cancer cases detected after a negative screening result and before the date of the next recommended screening. RESULTS A total of 339 cases of CRC (175 male: 164 female, 173 early stage: 166 advanced stage) were detected in the nine-year CRC screening period. The rate of right-sided CRCs was significantly higher in female (P < 0.01), advanced stage (P < 0.01), negative result previous year (P < 0.01), and symptom-negative (P < 0.01) participants than in each counterpart, respectively. The ratio of female (22/35; 62.9%) patients in Negative advanced CRCs tended to be high compared with that (40/83; 48.2%) in First advanced CRCs (P = 0.145). Overall, 22 (62.9%) of 35 Negative advanced CRCs and 28 (33.7%) of 83 First advanced CRCs were located in the right-sided colon, and the rate was significantly higher in Negative advanced CRCs (P < 0.01). In addition, the frequency of female patients was significantly higher in right-sided Negative advanced CRCs than in right-sided First advanced CRCs (P = 0.03). CONCLUSION The characteristics of Negative advanced CRC cases (female and right-sided colon) were similar to those of interval cancer reported so far. In the future, it will be necessary to introduce a screening program that is highly sensitive to right-sided CRC.
Collapse
Affiliation(s)
- Ryosuke Hasegawa
- Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504 Japan
| | - Kazuo Yashima
- Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504 Japan
| | - Yuichiro Ikebuchi
- Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504 Japan
| | - Shuji Sasaki
- Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504 Japan
| | - Akira Yoshida
- Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504 Japan
| | - Koichiro Kawaguchi
- Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504 Japan
| | - Hajime Isomoto
- Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504 Japan
| |
Collapse
|
|
48
|
Komor MA, Bosch LJ, Coupé VM, Rausch C, Pham TV, Piersma SR, Mongera S, Mulder CJ, Dekker E, Kuipers EJ, van de Wiel MA, Carvalho B, Fijneman RJ, Jimenez CR, Meijer GA, de Wit M. Proteins in stool as biomarkers for non-invasive detection of colorectal adenomas with high risk of progression. J Pathol 2020; 250:288-298. [PMID: 31784980 PMCID: PMC7065084 DOI: 10.1002/path.5369] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 10/07/2019] [Accepted: 11/28/2019] [Indexed: 12/15/2022]
Abstract
Screening to detect colorectal cancer (CRC) in an early or premalignant state is an effective method to reduce CRC mortality rates. Current stool-based screening tests, e.g. fecal immunochemical test (FIT), have a suboptimal sensitivity for colorectal adenomas and difficulty distinguishing adenomas at high risk of progressing to cancer from those at lower risk. We aimed to identify stool protein biomarker panels that can be used for the early detection of high-risk adenomas and CRC. Proteomics data (LC-MS/MS) were collected on stool samples from adenoma (n = 71) and CRC patients (n = 81) as well as controls (n = 129). Colorectal adenoma tissue samples were characterized by low-coverage whole-genome sequencing to determine their risk of progression based on specific DNA copy number changes. Proteomics data were used for logistic regression modeling to establish protein biomarker panels. In total, 15 of the adenomas (15.8%) were defined as high risk of progressing to cancer. A protein panel, consisting of haptoglobin (Hp), LAMP1, SYNE2, and ANXA6, was identified for the detection of high-risk adenomas (sensitivity of 53% at specificity of 95%). Two panels, one consisting of Hp and LRG1 and one of Hp, LRG1, RBP4, and FN1, were identified for high-risk adenomas and CRCs detection (sensitivity of 66% and 62%, respectively, at specificity of 95%). Validation of Hp as a biomarker for high-risk adenomas and CRCs was performed using an antibody-based assay in FIT samples from a subset of individuals from the discovery series (n = 158) and an independent validation series (n = 795). Hp protein was significantly more abundant in high-risk adenoma FIT samples compared to controls in the discovery (p = 0.036) and the validation series (p = 9e-5). We conclude that Hp, LAMP1, SYNE2, LRG1, RBP4, FN1, and ANXA6 may be of value as stool biomarkers for early detection of high-risk adenomas and CRCs. © 2019 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Collapse
Affiliation(s)
- Malgorzata A Komor
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.,Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | - Linda Jw Bosch
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Veerle Mh Coupé
- Department of Epidemiology and Biostatistics, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | - Christian Rausch
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Thang V Pham
- Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | - Sander R Piersma
- Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | - Sandra Mongera
- Department of Pathology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | - Chris Jj Mulder
- Department of Gastroenterology and Hepatology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Ernst J Kuipers
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Mark A van de Wiel
- Department of Epidemiology and Biostatistics, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | - Beatriz Carvalho
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Remond Ja Fijneman
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Connie R Jimenez
- Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | - Gerrit A Meijer
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Meike de Wit
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| |
Collapse
|
|
49
|
Diagnostic Accuracy of Stool Tests for Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors. J Clin Med 2020; 9:jcm9010190. [PMID: 31936745 PMCID: PMC7019558 DOI: 10.3390/jcm9010190] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 01/06/2020] [Accepted: 01/08/2020] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Hodgkin lymphoma (HL) survivors have an increased colorectal cancer (CRC) risk. Diagnostic accuracy of quantitative fecal immunochemical testing (FIT, OC Sensor) and/or a multi-target stool DNA test (mt-sDNA, Cologuard®) for advanced neoplasia (AN) was evaluated. METHODS 101 HL survivors underwent a surveillance colonoscopy and were asked to perform two stool tests (FIT and mt-sDNA). Advanced adenoma (AA), advanced serrated lesion (ASL), and AN (AA, ASL, CRC) were evaluated. Sensitivity, specificity, and area under the curve (AUC) for AN were calculated for different FIT cut-offs and mt-sDNA with colonoscopy as reference. RESULTS FIT and mt-sDNA were analyzed in 73 (72%) and 82 (81%) participants, respectively. AN was detected in 19 (26%) and 22 (27%), respectively. AN sensitivities for FIT cut-off of 10 ug Hb/g feces (FIT10) and mt-sDNA were 37% (95% confidence interval (CI): 16-62) and 68% (95% CI: 45-86), with corresponding specificities of 91% (95% CI: 80-97) and 70% (95% CI: 57-86), respectively. AUC for FIT was 0.68 (95% CI: 0.54-0.82) and for mt-sDNA 0.76 (95% CI: 0.63-0.89). CONCLUSIONS In HL survivors, mt-sDNA showed highest sensitivity but with relatively low specificity for AN. Cost-effectiveness analyses is necessary to determine the optimal surveillance strategy.
Collapse
|
|
50
|
Kooyker AI, Toes-Zoutendijk E, Opstal-van Winden AWJ, Spaander MCW, Buskermolen M, van Vuuren HJ, Kuipers EJ, van Kemenade FJ, Ramakers C, Thomeer MGJ, Dekker E, Nagtegaal ID, de Koning HJ, van Leerdam ME, Lansdorp-Vogelaar I. The second round of the Dutch colorectal cancer screening program: Impact of an increased fecal immunochemical test cut-off level on yield of screening. Int J Cancer 2020; 147:1098-1106. [PMID: 31853977 PMCID: PMC7383838 DOI: 10.1002/ijc.32839] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 11/08/2019] [Accepted: 11/11/2019] [Indexed: 12/18/2022]
Abstract
The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information‐system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut‐off halfway through the first round from 15 to 47 μg Hb/g feces on outcomes in the second round. Second round screening was done with a 47 μg Hb/g feces FIT cut‐off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non‐participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut‐off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut‐off were detected in the subsequent round. What's new? In 2014, the Netherlands implemented colorectal cancer (CRC) screening based on non‐invasive fecal immunochemical testing (FIT), which offers a practical approach for population‐based CRC detection. In the Dutch program's first round, to match local resources, FIT cut‐off was increased, resulting in reduced positivity rates and reduced colonoscopy referrals, at the cost of missing advanced neoplasias. The current study shows that many of these missed advanced neoplasias were detected in subsequent screening, suggesting that increased FIT cut‐off had marginal impact on screening outcome. The findings could benefit other CRC screening programs in establishing effective FIT cut‐offs.
Collapse
Affiliation(s)
- Arthur I Kooyker
- Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands.,Department of Gastroenterology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands
| | - Esther Toes-Zoutendijk
- Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands
| | | | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Maaike Buskermolen
- Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Hanneke J van Vuuren
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Ernst J Kuipers
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | | | - Chris Ramakers
- Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Maarten G J Thomeer
- Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers - Academic Medical Center, Amsterdam, The Netherlands
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Harry J de Koning
- Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Monique E van Leerdam
- Department of Gastroenterology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands
| | - Iris Lansdorp-Vogelaar
- Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands
| |
Collapse
|