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Digby J, Nobes J, Strachan JA, McCann R, Hall C, Fraser CG, Mowat C. Combining faecal haemoglobin, iron deficiency anaemia status and age can improve colorectal cancer risk prediction in patients attending primary care with bowel symptoms: a retrospective observational study. Gut 2025:gutjnl-2024-334248. [PMID: 40139747 DOI: 10.1136/gutjnl-2024-334248] [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: 11/04/2024] [Accepted: 03/13/2025] [Indexed: 03/29/2025]
Abstract
BACKGROUND In primary care, National Institute for Health and Care Excellence suspected cancer guidelines recommend measuring faecal haemoglobin (f-Hb) if colorectal cancer (CRC) is suspected, with a referral threshold of ≥10 µg Hb/g faeces defining a 3% risk, but most have a normal colonoscopy. OBJECTIVE Examine whether combining f-Hb, patient age and iron-deficient anaemia (IDA) status improves risk prediction. DESIGN Retrospective single-centre observational study of symptomatic patients who submitted contemporaneous f-Hb and full blood count (FBC) samples between December 2015 and December 2019. f-Hb was estimated using HM-JACKarc (Hitachi Chemical Diagnostics Systems). Patients were categorised by presence/absence of IDA. Incident CRC was identified via record linkage to the Scottish Cancer Registry. Kaplan-Meier estimates determined cumulative 1-year CRC risk by patient age, f-Hb result and presence of IDA. RESULTS Of 34 647 valid f-Hb results retrieved; 7889 (22.8%) had f-Hb≥10 µg Hb/g. Of these, 33 285 samples (96.1%) had associated FBC results of which 3000 (9.0%) had IDA. Overall, 571 incident CRC were recorded. The risk of CRC breached 3% in patients with f-Hb>99 µg Hb/g aged >40 years and reached 30% (19.4-41.0) with f-Hb>99 µg Hb/g in age >55 years plus IDA. 2029 f-Hb results (25.7%) were in the 10-19 µg Hb/g range of which 27 (1.3%) had CRC. In this subgroup, CRC risk did not exceed 3% in patients <85 years and no IDA. CONCLUSION Combining f-Hb, patient age and IDA status improves CRC risk prediction, identifies a low-risk group with f-Hb<20 µg Hb/g and no IDA and could inform revised referral guidance.
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Affiliation(s)
- Jayne Digby
- Centre for Research into Cancer Prevention and Screening, University of Dundee, Dundee, Scotland, UK
| | - Jennifer Nobes
- Division of Respiratory Medicine and Gastroenterology, University of Dundee, Dundee, UK
| | | | | | - Christopher Hall
- Health Informatics Centre, University of Dundee, Dundee, Scotland, UK
| | - Callum G Fraser
- Centre for Research into Cancer Prevention and Screening, University of Dundee, Dundee, Scotland, UK
| | - Craig Mowat
- Division of Respiratory Medicine and Gastroenterology, University of Dundee, Dundee, UK
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Arasaradnam RP, Krishnamoorthy A, Hull MA, Wheatstone P, Kvasnik F, Persaud KC. The Development and Optimisation of a Urinary Volatile Organic Compound Analytical Platform Using Gas Sensor Arrays for the Detection of Colorectal Cancer. SENSORS (BASEL, SWITZERLAND) 2025; 25:599. [PMID: 39943238 PMCID: PMC11820771 DOI: 10.3390/s25030599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 01/16/2025] [Accepted: 01/18/2025] [Indexed: 02/16/2025]
Abstract
The profile of Volatile Organic Compounds (VOCs) may help prioritise at-risk groups for early cancer detection. Urine sampling has been shown to provide good disease accuracy whilst being patient acceptable compared to faecal analysis. Thus, in this study, urine samples were examined using an electronic nose with metal oxide gas sensors and a solid-phase microextraction sampling system. A calibration dataset (derived from a previous study) with CRC-positive patients and healthy controls was used to train a radial basis function neural network. However, a blinded analysis failed to detect CRC accurately, necessitating an enhanced data-processing strategy. This new approach categorised samples by significant bowel diseases, including CRC and high-risk polyps. Retraining the neural network showed an area under the ROC curve of 0.88 for distinguishing CRC versus non-significant bowel disease (without CRC, polyps or inflammation). These findings suggest that, with appropriate training sets, urine VOC analysis could be a rapid, low-cost method for early detection of precancerous colorectal polyps and CRC.
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Affiliation(s)
- Ramesh P. Arasaradnam
- Institute of Precision Diagnostics & Translational Medicine, University Hospitals Coventry & Warwickshire, Coventry CV2 2DX, UK
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Leicester Cancer Research Centre, University of Leicester, Leicester LE1 7RH, UK
| | - Ashwin Krishnamoorthy
- Institute of Precision Diagnostics & Translational Medicine, University Hospitals Coventry & Warwickshire, Coventry CV2 2DX, UK
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
| | - Mark A. Hull
- Leeds Institute of Medical Research, St James’s University Hospital, University of Leeds, Leeds LS9 7TF, UK
| | - Peter Wheatstone
- Leeds Institute of Medical Research, St James’s University Hospital, University of Leeds, Leeds LS9 7TF, UK
| | - Frank Kvasnik
- Department of Chemical Engineering, The University of Manchester, Manchester M13 9PL, UK
| | - Krishna C. Persaud
- Department of Chemical Engineering, The University of Manchester, Manchester M13 9PL, UK
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Farkas NG, O'Brien J, Norman J, Steinke J, Yu KS, Whyte M, Jourdan I, Rockall T, Benton SC. Faecal haemoglobin concentration and colorectal cancer site, stage and grade in a symptomatic cohort. Colorectal Dis 2024; 26:2039-2045. [PMID: 39323004 DOI: 10.1111/codi.17187] [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: 06/23/2023] [Revised: 03/14/2024] [Accepted: 09/02/2024] [Indexed: 09/27/2024]
Abstract
AIM Minimal evidence exists regarding faecal immunochemical tests (FITs) for colorectal cancer (CRC) site, stage and grade in symptomatic patients. The primary aim is to determine any association between faecal haemoglobin concentration (f-Hb) (analysed with OC-Sensor™ Pledia) and these prognostic factors. The secondary aim is to determine the association between f-Hb and anaemia, microcytosis and iron deficiency (Hb, mean corpuscular volume [MCV] and ferritin). METHODOLOGY Symptomatic 2-week wait CRC patients with FIT were included (July 2019-October 2022). Median f-Hb and interquartile range according to sex, stage, grade and site (right-sided, caecum to transverse colon, R-CRC; left-sided, splenic flexure to rectum, L-CRC) were compared using the Mann-Whitney U test. Hb, MCV and ferritin were categorized into two groups and the median f-Hb was compared using the Mann-Whitney U test. RESULTS In all, 114 patients (57 women, 57 men) were studied; 46 had R-CRC (f-Hb = 113 μg Hb/g) and 68 had L-CRC (f-Hb = 342 μg Hb/g) (P = 0.07). Sixty-nine were moderately differentiated CRC (f-Hb = 183 μg Hb/g) and 29 were poorly differentiated (f-Hb = 866 μg Hb/g) (P = 0.04). By T-stage, 35 were early (T1/2) (f-Hb = 170 μg Hb/g) and 79 were advanced (T3/4) (f-Hb = 200 μg Hb/g) (P = 0.06). The relationship between f-Hb and Hb, MCV and ferritin was not significant. Poorly differentiated (P = 0.04) and later stage (P = 0.02) R-CRC had significantly lower f-Hb compared to L-CRC. CONCLUSIONS Right-sided CRC is associated with lower f-Hb than left. Poorly differentiated and later staged L-CRC had higher median f-Hb. These data add to existing evidence suggesting that FIT may be less sensitive for right-sided CRC. Strategies to mitigate the potential for missed or FIT-negative right-sided CRC are required.
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Affiliation(s)
- Nicholas G Farkas
- Minimal Access Therapy and Training Unit (MATTU), Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - James O'Brien
- Minimal Access Therapy and Training Unit (MATTU), Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - James Norman
- Minimal Access Therapy and Training Unit (MATTU), Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Jackie Steinke
- Minimal Access Therapy and Training Unit (MATTU), Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Kai Shing Yu
- Minimal Access Therapy and Training Unit (MATTU), Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
| | - Martin Whyte
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Iain Jourdan
- Minimal Access Therapy and Training Unit (MATTU), Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
| | - Tim Rockall
- Minimal Access Therapy and Training Unit (MATTU), Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
| | - Sally C Benton
- Department of Clinical Biochemistry, Royal Surrey County Hospital, Berkshire and Surrey Pathology Services, Guildford, Surrey, UK
- NHS Bowel Cancer Screening South of England Hub, Berkshire and Surrey Pathology Services, Royal Surrey County Hospital, Guildford, Surrey, UK
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Limsrivilai J, Yodmalai C, Chaemsupaphan T, Sattayalertyanyong O, Subdee N, Permpim P, Phaophu P, Kaosombatwattana U, Pausawasdi N, Riansuwan W, Charatcharoenwitthaya P, Pongprasobchai S. Evaluating the Efficacy of Fecal Immunochemical Test, Fecal Calprotectin, and Serum C-Reactive Protein in Diagnosing Patients With Chronic Lower Gastrointestinal Symptoms. Clin Transl Gastroenterol 2024; 15:e00747. [PMID: 38994833 PMCID: PMC11346899 DOI: 10.14309/ctg.0000000000000747] [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: 02/14/2024] [Accepted: 06/27/2024] [Indexed: 07/13/2024] Open
Abstract
INTRODUCTION Accurate early detection of ileocolonic lesions in patients with chronic lower gastrointestinal symptoms (LGISs) is often difficult due to the rarity of early-stage alarm signs. This study assesses the effectiveness of noninvasive blood and stool biomarkers in diagnosing ileocolonic lesions in patients with chronic LGISs undergoing colonoscopy. METHODS We conducted a prospective study between April 2020 and July 2022 involving patients with LGISs lasting a month or more. Before colonoscopy, we gathered clinical data, blood samples for C-reactive protein (CRP) and stool samples for fecal immunochemical test (FIT) and fecal calprotectin (FC) analysis. RESULTS Of 922 participants analyzed (average age 62 years, 37% male), 130 (14.1%) had significant colonoscopy findings, including cancer, advanced adenoma, and inflammatory conditions. Test effectiveness showed an area under the curve of 0.630 for alarm features, 0.643 for CRP, 0.781 for FIT, and 0.667 for FC. Combining stool tests with alarm features improved diagnostic precision. Those without alarm features had a high negative predictive value of 0.97 with low threshold FIT and FC, missing minimal significant lesions, and no cancer. For patients with alarm features, dual high-cutoff test positivity showed a positive predictive value of 0.67. Adding CRP to fecal tests did not enhance accuracy. DISCUSSION FIT and FC are valuable in evaluating LGISs. Negative results at low cutoffs can delay colonoscopy in limited resource settings while positive results at dual high cutoffs substantiate the need for the procedure.
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Affiliation(s)
- Julajak Limsrivilai
- Division of Gastroenterology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Chatrawee Yodmalai
- Division of Gastroenterology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Thanaboon Chaemsupaphan
- Division of Gastroenterology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Onuma Sattayalertyanyong
- Division of Gastroenterology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nichcha Subdee
- Division of Gastroenterology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Parinya Permpim
- Division of Gastroenterology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Phutthaphorn Phaophu
- Division of Gastroenterology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Uayporn Kaosombatwattana
- Division of Gastroenterology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nonthalee Pausawasdi
- Division of Gastroenterology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Woramin Riansuwan
- Colorectal Surgery Unit, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | | | - Supot Pongprasobchai
- Division of Gastroenterology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Kononova E, Mežmale L, Poļaka I, Veliks V, Anarkulova L, Vilkoite I, Tolmanis I, Ļeščinska AM, Stonāns I, Pčolkins A, Mochalski P, Leja M. Breath Fingerprint of Colorectal Cancer Patients Based on the Gas Chromatography-Mass Spectrometry Analysis. Int J Mol Sci 2024; 25:1632. [PMID: 38338911 PMCID: PMC10855950 DOI: 10.3390/ijms25031632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 01/25/2024] [Accepted: 01/26/2024] [Indexed: 02/12/2024] Open
Abstract
The human body emits a multitude of volatile organic compounds (VOCs) via tissues and various bodily fluids or exhaled breath. These compounds collectively create a distinctive chemical profile, which can potentially be employed to identify changes in human metabolism associated with colorectal cancer (CRC) and, consequently, facilitate the diagnosis of this disease. The main goal of this study was to investigate and characterize the VOCs' chemical patterns associated with the breath of CRC patients and controls and identify potential expiratory markers of this disease. For this purpose, gas chromatography-mass spectrometry was applied. Collectively, 1656 distinct compounds were identified in the breath samples provided by 152 subjects. Twenty-two statistically significant VOCs (p-xylene; hexanal; 2-methyl-1,3-dioxolane; 2,2,4-trimethyl-1,3-pentanediol diisobutyrate; hexadecane; nonane; ethylbenzene; cyclohexanone; diethyl phthalate; 6-methyl-5-hepten-2-one; tetrahydro-2H-pyran-2-one; 2-butanone; benzaldehyde; dodecanal; benzothiazole; tetradecane; 1-dodecanol; 1-benzene; 3-methylcyclopentyl acetate; 1-nonene; toluene) were observed at higher concentrations in the exhaled breath of the CRC group. The elevated levels of these VOCs in CRC patients' breath suggest the potential for these compounds to serve as biomarkers for CRC.
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Affiliation(s)
- Elīna Kononova
- Institute of Clinical and Preventive Medicine, University of Latvia, LV-1586 Riga, Latvia; (E.K.); (I.P.); (V.V.); (L.A.); (A.M.Ļ.); (I.S.); (A.P.); (M.L.)
- Faculty of Medicine, Riga Stradins University, LV-1007 Riga, Latvia;
| | - Linda Mežmale
- Institute of Clinical and Preventive Medicine, University of Latvia, LV-1586 Riga, Latvia; (E.K.); (I.P.); (V.V.); (L.A.); (A.M.Ļ.); (I.S.); (A.P.); (M.L.)
- Riga East University Hospital, LV-1038 Riga, Latvia
- Health Centre 4, LV-1012 Riga, Latvia;
| | - Inese Poļaka
- Institute of Clinical and Preventive Medicine, University of Latvia, LV-1586 Riga, Latvia; (E.K.); (I.P.); (V.V.); (L.A.); (A.M.Ļ.); (I.S.); (A.P.); (M.L.)
- Department of Modelling and Simulation, Riga Technical University, LV-1048 Riga, Latvia
| | - Viktors Veliks
- Institute of Clinical and Preventive Medicine, University of Latvia, LV-1586 Riga, Latvia; (E.K.); (I.P.); (V.V.); (L.A.); (A.M.Ļ.); (I.S.); (A.P.); (M.L.)
| | - Linda Anarkulova
- Institute of Clinical and Preventive Medicine, University of Latvia, LV-1586 Riga, Latvia; (E.K.); (I.P.); (V.V.); (L.A.); (A.M.Ļ.); (I.S.); (A.P.); (M.L.)
- Health Centre 4, LV-1012 Riga, Latvia;
- Liepaja Regional Hospital, LV-3414 Liepaja, Latvia
| | - Ilona Vilkoite
- Health Centre 4, LV-1012 Riga, Latvia;
- Department of Doctoral Studies, Riga Stradins University, LV-1007 Riga, Latvia
- Digestive Diseases Centre GASTRO, LV-1079 Riga, Latvia
| | - Ivars Tolmanis
- Faculty of Medicine, Riga Stradins University, LV-1007 Riga, Latvia;
- Digestive Diseases Centre GASTRO, LV-1079 Riga, Latvia
| | - Anna Marija Ļeščinska
- Institute of Clinical and Preventive Medicine, University of Latvia, LV-1586 Riga, Latvia; (E.K.); (I.P.); (V.V.); (L.A.); (A.M.Ļ.); (I.S.); (A.P.); (M.L.)
- Riga East University Hospital, LV-1038 Riga, Latvia
- Digestive Diseases Centre GASTRO, LV-1079 Riga, Latvia
| | - Ilmārs Stonāns
- Institute of Clinical and Preventive Medicine, University of Latvia, LV-1586 Riga, Latvia; (E.K.); (I.P.); (V.V.); (L.A.); (A.M.Ļ.); (I.S.); (A.P.); (M.L.)
| | - Andrejs Pčolkins
- Institute of Clinical and Preventive Medicine, University of Latvia, LV-1586 Riga, Latvia; (E.K.); (I.P.); (V.V.); (L.A.); (A.M.Ļ.); (I.S.); (A.P.); (M.L.)
- Riga East University Hospital, LV-1038 Riga, Latvia
- Faculty of Medicine, University of Latvia, LV-1586 Riga, Latvia
| | - Pawel Mochalski
- Institute for Breath Research, University of Innsbruck, 6020 Innsbruck, Austria;
- Institute of Chemistry, Jan Kochanowski University of Kielce, 25-369 Kielce, Poland
| | - Mārcis Leja
- Institute of Clinical and Preventive Medicine, University of Latvia, LV-1586 Riga, Latvia; (E.K.); (I.P.); (V.V.); (L.A.); (A.M.Ļ.); (I.S.); (A.P.); (M.L.)
- Riga East University Hospital, LV-1038 Riga, Latvia
- Digestive Diseases Centre GASTRO, LV-1079 Riga, Latvia
- Faculty of Medicine, University of Latvia, LV-1586 Riga, Latvia
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Hampton JS, Kenny RP, Rees CJ, Hamilton W, Eastaugh C, Richmond C, Sharp L. The performance of FIT-based and other risk prediction models for colorectal neoplasia in symptomatic patients: a systematic review. EClinicalMedicine 2023; 64:102204. [PMID: 37781155 PMCID: PMC10541467 DOI: 10.1016/j.eclinm.2023.102204] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 08/21/2023] [Accepted: 08/28/2023] [Indexed: 10/03/2023] Open
Abstract
Background Colorectal cancer (CRC) incidence and mortality are increasing internationally. Endoscopy services are under significant pressure with many overwhelmed. Faecal immunochemical testing (FIT) has been advocated to identify a high-risk population of symptomatic patients requiring definitive investigation by colonoscopy. Combining FIT with other factors in a risk prediction model could further improve performance in identifying those requiring investigation most urgently. We systematically reviewed performance of models predicting risk of CRC and/or advanced colorectal polyps (ACP) in symptomatic patients, with a particular focus on those models including FIT. Methods The review protocol was published on PROSPERO (CRD42022314710). Searches were conducted from database inception to April 2023 in MEDLINE, EMBASE, Cochrane libraries, SCOPUS and CINAHL. Risk of bias of each study was assessed using The Prediction study Risk Of Bias Assessment Tool. A narrative synthesis based on the guidelines for Synthesis Without Meta-Analysis was performed due to study heterogeneity. Findings We included 62 studies; 23 included FIT (n = 22) or guaiac Faecal Occult Blood Testing (n = 1) combined with one or more other variables. Twenty-one studies were conducted solely in primary care. Generally, prediction models including FIT consistently had good discriminatory ability for CRC/ACP (i.e. AUC >0.8) and performed better than models without FIT although some models without FIT also performed well. However, many studies did not present calibration and internal and external validation were limited. Two studies were rated as low risk of bias; neither model included FIT. Interpretation Risk prediction models, including and not including FIT, show promise for identifying those most at risk of colorectal neoplasia. Substantial limitations in evidence remain, including heterogeneity, high risk of bias, and lack of external validation. Further evaluation in studies adhering to gold standard methodology, in appropriate populations, is required before widespread adoption in clinical practice. Funding National Institute for Health and Care Research (NIHR) [Health Technology Assessment Programme (HTA) Programme (Project number 133852).
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Affiliation(s)
- James S. Hampton
- Population Health Sciences Institute, Newcastle University, United Kingdom
- Department of Gastroenterology, South Tyneside and Sunderland NHS Foundation Trust, United Kingdom
| | - Ryan P.W. Kenny
- Evidence Synthesis Group, The Catalyst, Population Health Sciences Institute, Newcastle University, United Kingdom
- National Institute for Health and Care Research Innovation Observatory, The Catalyst, Newcastle University, United Kingdom
| | - Colin J. Rees
- Population Health Sciences Institute, Newcastle University, United Kingdom
- Department of Gastroenterology, South Tyneside and Sunderland NHS Foundation Trust, United Kingdom
| | - William Hamilton
- College of Medicine and Health, University of Exeter, United Kingdom
| | - Claire Eastaugh
- Evidence Synthesis Group, The Catalyst, Population Health Sciences Institute, Newcastle University, United Kingdom
- National Institute for Health and Care Research Innovation Observatory, The Catalyst, Newcastle University, United Kingdom
| | - Catherine Richmond
- Evidence Synthesis Group, The Catalyst, Population Health Sciences Institute, Newcastle University, United Kingdom
- National Institute for Health and Care Research Innovation Observatory, The Catalyst, Newcastle University, United Kingdom
| | - Linda Sharp
- Population Health Sciences Institute, Newcastle University, United Kingdom
| | - COLOFIT Research Team
- Population Health Sciences Institute, Newcastle University, United Kingdom
- Department of Gastroenterology, South Tyneside and Sunderland NHS Foundation Trust, United Kingdom
- Evidence Synthesis Group, The Catalyst, Population Health Sciences Institute, Newcastle University, United Kingdom
- National Institute for Health and Care Research Innovation Observatory, The Catalyst, Newcastle University, United Kingdom
- College of Medicine and Health, University of Exeter, United Kingdom
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Lanas Á, Balaguer F, Sánchez‐Luengo M, Hijos‐Mallada G, Hernández‐Mesa G, Piñero M, Castillo J, Ocaña T, Cubiella J, Crespo A, Iglesias Á, Medeiros I, Cacho G, Jover‐Martínez R, Alustiza M, Diaz‐Tasende J, Poves C, Macedo G, Quintero E. Fecal occult blood and calprotectin testing to prioritize primary care patients for colonoscopy referral: The advantage study. United European Gastroenterol J 2023; 11:692-699. [PMID: 37614054 PMCID: PMC10493338 DOI: 10.1002/ueg2.12446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 06/26/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND Colonoscopy is the gold standard for colorectal cancer (CRC) diagnosis and screening, but endoscopy services are usually overburdened. This study aims to investigate the usefulness of fecal hemoglobin (fHb) and calprotectin (FC) for the identification of patients with high probability of CRC who need urgent referral. METHODS In a multicenter prospective study, we enrolled symptomatic patients referred from primary care for colonoscopy. Prior to bowel preparation, fHb and FC quantitative tests were performed. The diagnostic performance was estimated for each biomarker/combination. We built a multivariable predictive model based on logistic regression, translated to a nomogram and a risk calculator to assist clinicians in the decision-making process. RESULTS The study included 1224 patients, of whom 69 (5.6%) had CRC. At the fHb cut-offs of >0 and 10 μg/g, the negative predictive values for CRC were 98.8% (95% confidence interval 97.8%-99.3%) and 98.6% (95%CI 97.7%-99.1%), and the sensitivities were 85.5% (95%CI 75.0%-92.8%) and 79.7% (95%CI 68.3%-88.4%), respectively. When we added the cut-off of 150 μg/g of FC to both fHb thresholds, the sensitivity of fecal tests improved. In the multivariate logistic regression model, the concentration of fHb was an independent predictor for CRC; age and gender were also independently associated with CRC. CONCLUSIONS fHb and FC are useful as part of a triage tool to identify those symptomatic patients with high probability of CRC. This can be easily applied by physicians to prioritize high-risk patients for urgent colonoscopy.
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Affiliation(s)
- Ángel Lanas
- University Clinic Hospital Lozano Blesa. University of Zaragoza. IIS Aragón. CIBERHEDZaragozaSpain
| | - Francesc Balaguer
- Department of GastroenterologyHospital Clínic de BarcelonaInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)University of BarcelonaBarcelonaSpain
| | - Marta Sánchez‐Luengo
- Department of GastroenterologyHospital Clínico Universitario Lozano BlesaZaragozaSpain
| | - Gonzalo Hijos‐Mallada
- Department of GastroenterologyHospital Clínico Universitario Lozano BlesaZaragozaSpain
| | - Goretti Hernández‐Mesa
- Department of GastroenterologyHospital Universitario de CanariasInstituto Universitario de Tecnologías Biomédicas (ITB) & Centro de Investigación Biomédica de Canarias (CIBICAN)Universidad de La LagunaTenerifeSpain
| | - Melisa Piñero
- Department of GastroenterologyHospital Universitario de CanariasInstituto Universitario de Tecnologías Biomédicas (ITB) & Centro de Investigación Biomédica de Canarias (CIBICAN)Universidad de La LagunaTenerifeSpain
| | - Joaquin Castillo
- Department of GastroenterologyHospital Clínic de BarcelonaInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)University of BarcelonaBarcelonaSpain
| | - Teresa Ocaña
- Department of GastroenterologyHospital Clínico Universitario Lozano BlesaZaragozaSpain
| | - Joaquín Cubiella
- Department of GastroenterologyComplexo Hospitalario Universitario de OurenseOurenseSpain
| | - Anais Crespo
- Department of GastroenterologyComplexo Hospitalario Universitario de OurenseOurenseSpain
| | - Águeda Iglesias
- Department of GastroenterologyComplexo Hospitalario Universitario de OurenseOurenseSpain
| | - Isabel Medeiros
- Department of GastroenterologyHospital Espirito Santo de ÉvoraÉvoraPortugal
| | - Guillermo Cacho
- Department of GastroenterologyHospital Universitario Fundación AlcorcónMadridSpain
| | | | - Miren Alustiza
- Department of GastroenterologyHospital General Universitario de AlicanteMadridSpain
| | - José Diaz‐Tasende
- Department of GastroenterologyHospital Universitario 12 de OctubreMadridSpain
| | - Carmen Poves
- Department of GastroenterologyHospital Clínico Universitario San CarlosMadridSpain
| | - Guilherme Macedo
- Department of GastroenterologyCentro Hospitalar São JoãoPortoPortugal
| | - Enrique Quintero
- Department of GastroenterologyHospital Universitario de CanariasInstituto Universitario de Tecnologías Biomédicas (ITB) & Centro de Investigación Biomédica de Canarias (CIBICAN)Universidad de La LagunaTenerifeSpain
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Murray J, Kok KB, Ayling RM. Fecal Calprotectin in Gastrointestinal Disease. Clin Chem 2023:7179811. [PMID: 37228058 DOI: 10.1093/clinchem/hvad051] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 03/14/2023] [Indexed: 05/27/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) comprises a group of chronic conditions characterized by relapsing and remitting inflammation of the gastrointestinal tract. The incidence is increasing worldwide, and the therapeutic options for management are expanding. Endoscopy is the gold standard investigation for diagnosis of IBD and for assessing mucosal healing, which is increasingly being used as a measure of disease control. However, it is an invasive procedure that is unpleasant for patients and expensive and time-consuming for hospitals. Fecal calprotectin has been shown to be an accurate surrogate marker of gastrointestinal inflammation in IBD. CONTENT Fecal calprotectin was initially used for the diagnosis of IBD but is now recognized as having a role in assisting in assessment of disease activity, prediction of relapse, and informing decisions around therapy and may help to minimize requirement for endoscopy. However, there are various preanalytical and analytical factors that can affect interpretation of the results; these need to be understood to optimize clinical care. SUMMARY Preanalytical and analytical factors that can potentially influence fecal calprotectin concentrations are examined, and an overview is provided of clinical situations in which fecal calprotectin is commonly measured.
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Affiliation(s)
- Jennifer Murray
- Department of Gastroenterology, Barts Health NHS Trust, Royal London Hospital, London, United Kingdom
| | - Klaartje B Kok
- Department of Gastroenterology, Barts Health NHS Trust, Royal London Hospital, London, United Kingdom
| | - Ruth M Ayling
- Department of Clinical Biochemistry, Barts Health NHS Trust, Royal London Hospital, London, United Kingdom
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9
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Zhu M, Fan L, Han M, Zhu S, Zhang S, Shi H. The usefulness of fecal hemoglobin and calprotectin tests in diagnosing significant bowel diseases: a prospective study. Scand J Gastroenterol 2023; 58:368-374. [PMID: 36260495 DOI: 10.1080/00365521.2022.2133551] [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] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Although colonoscopy remains the gold standard for determining bowel diseases, it's invasive and expensive. New non-invasive diagnostic methods are urgently needed as an initial screening modality. We aimed to investigate the value of fecal calprotectin (FC) and fecal immunochemical test (FIT) in differentiation of significant and non- significant bowel diseases. METHODS In this prospective study, consecutive individuals were included if they underwent colonoscopy for symptoms of lower gastrointestinal (GI) tract, positive fecal occult blood test, surveillance for IBD or colorectal cancer (CRC) screening. Diagnostic value of FC and FIT in discriminating significant bowel diseases (advanced neoplasia, active inflammatory bowel diseases or bowel inflammation due to other causes) and non-significant bowel diseases (normal, asymptomatic diverticulum, non-adenomatous polyp, or non-advanced neoplasia) were evaluated. RESULTS Among 201 individuals included, 107 patients had significant bowel diseases. FC and FIT had an area under the curve (AUC) of 0.722 (95% confidence interval [CI] 0.653-0.792) and 0.797 (95%CI 0.734-0.860), respectively, for determining significant bowel diseases. Combination of FC and FIT predicted significant bowel diseases with an AUC, sensitivity, specificity, and accuracy of 0.832 (95% CI 0.775-0.890), 77.6%, 74.5%, and 76.1%, respectively. Moreover, combination of FC and FIT was more sensitive among patients with lower GI symptoms than asymptomatic individuals (80.8% vs. 74.1%) to identify significant bowel diseases. CONCLUSIONS A single measurement of FC or FIT is not sufficiently accurate to identify patients with significant bowel disease. However, combination of FC and FIT can help increase the sensitivity, especially in patients with lower GI symptoms.
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Affiliation(s)
- Min Zhu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China
| | - Liqiaona Fan
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China
| | - Muzhou Han
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China
| | - Siying Zhu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China
| | - Haiyun Shi
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China
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10
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Hijos-Mallada G, Saura N, Lué A, Velamazan R, Nieto R, Navarro M, Arechavaleta S, Chueca E, Gomollon F, Lanas A, Sostres C. A Point-of-Care Faecal Test Combining Four Biomarkers Allows Avoidance of Normal Colonoscopies and Prioritizes Symptomatic Patients with a High Risk of Colorectal Cancer. Cancers (Basel) 2023; 15:cancers15030721. [PMID: 36765678 PMCID: PMC9913693 DOI: 10.3390/cancers15030721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 01/18/2023] [Accepted: 01/21/2023] [Indexed: 01/26/2023] Open
Abstract
Most colonoscopies performed to evaluate gastrointestinal symptoms detect only non-relevant pathologies. We aimed to evaluate the diagnostic accuracy of a qualitative point-of-care (POC) test combining four biomarkers (haemoglobin, transferrin, calprotectin, and lactoferrin), a quantitative faecal immunochemical test (FIT) for haemoglobin, and a quantitative faecal calprotectin (FC) test in symptomatic patients prospectively recruited. Colorectal cancer (CRC), adenoma requiring surveillance, inflammatory bowel disease (IBD), microscopic colitis, and angiodysplasia were considered significant pathologies. A total of 571 patients were included. Significant pathology was diagnosed in 118 (20.7%), including 30 CRC cases (5.3%). The POC test yielded the highest negative predictive values: 94.8% for a significant pathology and 100% for CRC or IBD if the four markers turned negative (36.8% of the patients). Negative predictive values of FIT, FC, and its combination for diagnosis of a significant pathology were 88.4%, 87.6%, and 90.8%, respectively. Moreover, the positive predictive value using the POC test was 82.3% for significant pathology when all biomarkers tested positive (6% of the patients), with 70.6% of these patients diagnosed with CRC or IBD. The AUC of the POC test was 0.801 (95%CI 0.754-0.848) for the diagnosis of a significant pathology. Therefore, this POC faecal test allows the avoidance of unnecessary colonoscopies and prioritizes high risk symptomatic patients.
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Affiliation(s)
- Gonzalo Hijos-Mallada
- Servicio de Aparato Digestivo, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain
- Correspondence:
| | - Nuria Saura
- Servicio de Aparato Digestivo, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain
| | - Alberto Lué
- Servicio de Aparato Digestivo, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain
| | - Raúl Velamazan
- Servicio de Aparato Digestivo, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain
| | - Rocío Nieto
- Departamento de Medicina, Universidad de Zaragoza, 50009 Zaragoza, Spain
| | - Mercedes Navarro
- Servicio de Aparato Digestivo, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain
| | | | - Eduardo Chueca
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain
| | - Fernando Gomollon
- Servicio de Aparato Digestivo, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain
- Departamento de Medicina, Universidad de Zaragoza, 50009 Zaragoza, Spain
- CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
| | - Angel Lanas
- Servicio de Aparato Digestivo, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain
- Departamento de Medicina, Universidad de Zaragoza, 50009 Zaragoza, Spain
- CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
| | - Carlos Sostres
- Servicio de Aparato Digestivo, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain
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11
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Delson D, Ward M, Haddock R, Nobes J, Digby J, Strachan JA, Mowat C. Impact of faecal haemoglobin based triage of bowel symptoms presenting to primary care on colorectal cancer diagnosis. Colorectal Dis 2022; 25:787-793. [PMID: 36495081 DOI: 10.1111/codi.16451] [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: 02/28/2022] [Revised: 10/20/2022] [Accepted: 11/02/2022] [Indexed: 12/30/2022]
Abstract
AIM Faecal immunochemical testing (FIT) for faecal haemoglobin was introduced into primary care in National Health Service Tayside in 2015 as an adjunct to clinical assessment of new bowel symptoms. We aimed to assess the impact of FIT-based triage in primary care on colorectal cancer (CRC) diagnosis. METHOD Cancer audit data between January 2016 and December 2019 were reviewed to identify all patients diagnosed locally with CRC. The mode of presentation and stage at diagnosis were noted and patient records were interrogated to identify whether FIT and full blood count (FBC) had been performed prior to referral. Results were compared between the FIT and non-FIT groups. RESULTS In all, 1245 patients were diagnosed with CRC of whom 581 (46.7%) presented through primary care. FIT was performed prior to referral in 440/581 (75.7%), with the proportion increasing from 62.3% in 2016 to 85.8% in 2019. At faecal haemoglobin ≥10 μg Hb/g faeces, sensitivity for CRC was 94.1%. Over the study period the annual proportion of non-emergency presentations increased significantly; presentations from primary care increased from 43.1% to 53.5% (P = 0.0096). After excluding non-FIT patients who had an overt CRC at referral, there was no difference in stage at diagnosis between FIT and non-FIT cancers. Safety-netting with FBC was widely used in our cohort with 97.3% of FIT patients having also had FBC. CONCLUSION FIT-based triage of new bowel symptoms in primary care is associated with increased non-emergency presentation of CRC but this did not influence stage at diagnosis.
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Affiliation(s)
- Dwi Delson
- School of Medicine, University of Dundee, Dundee, UK
| | - Mark Ward
- School of Medicine, University of Dundee, Dundee, UK
| | | | - Jennifer Nobes
- School of Medicine, University of Dundee, Dundee, UK.,Department of Blood Sciences, Ninewells Hospital, Dundee, UK
| | - Jayne Digby
- School of Medicine, University of Dundee, Dundee, UK
| | - Judith A Strachan
- School of Medicine, University of Dundee, Dundee, UK.,Department of Blood Sciences, Ninewells Hospital, Dundee, UK
| | - Craig Mowat
- School of Medicine, University of Dundee, Dundee, UK.,Department of Gastroenterology, Ninewells Hospital, Dundee, UK
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12
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Booth R, Carten R, D'Souza N, Westwood M, Kleijnen J, Abulafi M. Role of the faecal immunochemical test in patients with risk-stratified suspected colorectal cancer symptoms: A systematic review and meta-analysis to inform the ACPGBI/BSG guidelines. THE LANCET REGIONAL HEALTH. EUROPE 2022; 23:100518. [PMID: 36212984 PMCID: PMC9535300 DOI: 10.1016/j.lanepe.2022.100518] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Background The UK National Institute for Health and Care Excellence (NICE), recommended in 2017 the use of the faecal immunochemical test (FIT) to guide investigations in patients presenting with NICE-defined low-risk symptoms suspicious for colorectal cancer (CRC). At that time, NICE did not recommend FIT use for high-risk symptoms. This is the first systematic review to evaluate the diagnostic accuracy of FIT in NICE-defined high and low-risk symptoms and was designed to inform the joint ACPGBI/BSG guidelines. Methods We performed a systematic literature review and meta-analysis. PROSPERO registration number CRD42021224674. Medline and EMBASE databases were searched from inception to 31st March 2022. We included studies recruiting adult patients presenting with suspected CRC symptoms in whom FIT was performed and diagnostic accuracy data for CRC detection could be derived at a limit of detection (LoD) and/or 10 µg haemoglobin/gram faeces threshold in four commonly used analysers. FIT performance was assessed for high-risk, low-risk and individual symptoms where possible. Bivariate meta-analysis was performed where study numbers allowed. Findings Thirty-one studies (79566 patients) met inclusion criteria. At 10 µg/g, for "all symptoms" (n = 35,945) sensitivity and specificity were 91.0% (95% CI: 88.9, 92.7) and 75.2% (95% CI: 69.6, 80.1); for "high-risk" symptoms (n = 18,264), 88.7% (95% CI: 84.4, 92.0) and 78.5% (95% CI: 73.0, 83.2); and for "low-risk" symptoms (n = 2161), 88.7% (95% CI: 78.1, 95.3) and 88.5% (95% CI: 87.1, 89.9), respectively. At LoD, for "all symptoms" (n = 26,056) sensitivity and specificity were 94.7% (95% CI: 90.5, 97.1) and 66.5% (95% CI: 58.7, 73.6); for "high-risk" symptoms (n = 16,768), 92.8% (95% CI: 86.4, 96.3) and 70.3% (95% CI: 66.5, 73.8); and for "low-risk" symptoms (n = 2082), 94.7% (95% CI: 85.4, 98.9) and 71.9% (95% CI: 69.9, 73.9), respectively. Summary estimates were similar across different analysers. Interpretation FIT sensitivity for CRC detection is maximised at the LoD; its performance is similar in high and low-risk symptoms, and across different analysers where a common threshold is used. FIT performance for CRC detection is adequate and transferrable to clinical diagnostic pathways. Funding This review was part-funded by NHS England awarded to RM Partners. RB and RC were funded by research fellowships awarded by Croydon University Hospital.
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13
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Shu T, Wu K, Guo Y, He Q, Song X, Shan J, Wu L, Liu J, Wang Z, Liu L, Sun X. Evaluation of fecal SYPL1 as a diagnostic biomarker in colorectal cancer. Clin Biochem 2022; 103:8-15. [PMID: 35218739 DOI: 10.1016/j.clinbiochem.2022.02.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 02/06/2022] [Accepted: 02/21/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND At present, there is still no ideal non-invasive biomarker for colorectal cancer (CRC) screening. Previously, we foundserum synaptophysin like 1 (SYPL1) served as a potential biomarker for CRC diagnosis. However, whether fecal SYPL1 (fSYPL1) are more sensitive and specific for CRC remains unclear. METHODS We analyzed fSYPL1 in controls (n = 70), adenoma patients (n = 80), CRC patients (n = 150) and postoperative CRC patients (n = 25) by ELISA. RESULTS SYPL1 was stable in feces. The fSYPL1 levels were significantly higher in CRC patients than in either controls or adenoma patients (P < 0.0001). ROC curves showed that fSYPL1 performed superbly in distinguishing CRC patients from controls (AUC = 0.947; 95% CI: 0.920-0.974, P < 0.0001, sensitivity: 80.67%, specificity: 100.00%), which showed much stronger performance than the traditional biomarkers (FOBT, CEA and CA19-9). Meanwhile, the fSYPL1 level positively correlated with tumor size, tumor invasion, lymph node invasion and clinical stage (P < 0.05). In addition, the detection rate of fSYPL1 was high in early CRC (75.00% in stage I and II). The fSYPL1 levels in CRC patients declined substantially after surgery (P = 0.0002). By means of a lower cut off level, 73.58% of high-risk adenomas were detected. The combination of fSYPL1 and FOBT performed better than the combination of plasma SYPL1, CEA and CA199 in distinguishing CRC patients from controls. CONCLUSION The fSYPL1 might be a potential biomarker for CRC screening, early diagnosis, prognosis prediction and therapeutic effect monitoring.
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Affiliation(s)
- Tao Shu
- Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Kaiwen Wu
- School of Medicine, Southwest Jiaotong University, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan 610031, China
| | - Yuanbiao Guo
- Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Affiliated Hospital of Chongqing Medical University, Chengdu, Sichuan 610031, China
| | - Qiao He
- Department of Clinical Laboratory, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610031, China
| | - Xiaoyu Song
- Department of Clinical Laboratory, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610031, China
| | - Jing Shan
- Department of Gastroenterology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Affiliated Hospital of Chongqing Medical University, Chengdu, Sichuan 610031, China
| | - Liping Wu
- Department of Gastroenterology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Affiliated Hospital of Chongqing Medical University, Chengdu, Sichuan 610031, China
| | - Jia Liu
- School of Medicine, Southwest Jiaotong University, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan 610031, China
| | - Zhiming Wang
- School of Medicine, Southwest Jiaotong University, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan 610031, China
| | - Lei Liu
- Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Affiliated Hospital of Chongqing Medical University, Chengdu, Sichuan 610031, China.
| | - Xiaobin Sun
- Department of Gastroenterology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Department of Gastroenterology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Affiliated Hospital of Chongqing Medical University, Chengdu, Sichuan 610031, China.
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14
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Ross FA, Park JH, Mansouri D, Combet E, Horgan PG, McMillan DC, Roxburgh CSD. The role of faecal calprotectin in diagnosis and staging of colorectal neoplasia: a systematic review and meta-analysis. BMC Gastroenterol 2022; 22:176. [PMID: 35397505 PMCID: PMC8994317 DOI: 10.1186/s12876-022-02220-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 03/16/2022] [Indexed: 11/10/2022] Open
Abstract
Introduction The presence of inflammation is a key hallmark of cancer and, plays an important role in disease progression and survival in colorectal cancer (CRC). Calprotectin detected in the faeces is a sensitive measure of colonic inflammation. The role of FC as a diagnostic test that may categorise patients by risk of neoplasia is poorly defined. This systematic review and meta-analysis aims to characterise the relationship between elevations of FC and colorectal neoplasia. Methods A systematic review was performed using the keywords (MESH terms) and a statistical and meta-analysis was performed. Results A total of 35 studies are included in this review. CRC patients are more likely than controls to have an elevated FC OR 5.19, 95% CI 3.12–8.62, p < 0.001 with a heterogeneity (I2 = 27%). No tumour characteristics significantly correlated with FC, only stage of CRC shows signs that it may potentially correlate with FC. Conclusion FC levels are significantly higher in CRC, with high sensitivity. Its low specificity prevents it from being used to diagnose or screen for CRC. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-022-02220-1.
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15
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Bradley C, Hee SW, Andronis L, Persaud K, Hull MA, Todd J, Taylor-Phillips S, Smith S, Constable R, Waugh N, Arasaradnam RP. REducing Colonoscopies in patients without significant bowEl DiseasE: the RECEDE Study - protocol for a prospective diagnostic accuracy study. BMJ Open 2022; 12:e058559. [PMID: 35354626 PMCID: PMC8968545 DOI: 10.1136/bmjopen-2021-058559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
INTRODUCTION Demand for colonoscopies and CT colonography (CTC) is exceeding capacity in National Health Service Trusts. In many patients colonoscopies and CTCs show no significant bowel disease (SBD). Faecal Immunochemical Testing (FIT) is being introduced to prioritise patients for colonoscopies but is insufficient to identify non-SBD patients meaning colonoscopy and CTC demand remains high. The REducing Colonoscopies in patients without significant bowEl DiseasE (RECEDE) study aims to test urine volatile organic compound (VOC) analysis alongside FIT to improve detection of SBD and to reduce the number of colonoscopies and CTCs. METHODS AND ANALYSIS This is a multicentre, prospective diagnostic accuracy study evaluating whether stool FIT plus urine VOC compared with stool FIT alone improves detection of SBD in patients referred for colonoscopy or CTC due to persistent lower gastrointestinal symptoms. To ensure SBD is not missed, the dual test requires a high sensitivity, set at 97% with 95% CI width of 5%. Our assumption is that to achieve this sensitivity requires 200 participants with SBD. Further assuming 19% of all participants will have SBD and 55% of all participants will return both stool and urine samples we will recruit 1915 participants. The thresholds for FIT and VOC results diagnosing SBD have been pre-set. If either FIT or VOC exceeds the respective threshold, the participant will be classed as having suspected SBD. As an exploratory analysis we will be testing different thresholds. The reference comparator will be a complete colonoscopy or CTC. Secondary outcomes will look at optimising the FIT and VOC thresholds for SBD detection. An economic evaluation, using a denovo decision analytic model, will be carried out determine the costs, benefits and overall cost-effectiveness of FIT +VOC vs FIT followed by colonoscopy. ETHICS AND DISSEMINATION Ethical approval was obtained by Liverpool Central Research Ethics Committee (20/NW/0346). TRIAL REGISTRATION NUMBER RECEDE is registered on Clinicaltrials.gov NCT04516785 & ISRCTN14982373. This protocol was written and published before results of the trial were available.
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Affiliation(s)
- Christopher Bradley
- Research & Development, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Siew Wan Hee
- Warwick Clinical Trials Unit, University of Warwick, Coventry, UK
| | - Lazaros Andronis
- Warwick Clinical Trials Unit, University of Warwick, Coventry, UK
| | - Krishna Persaud
- Department of Chemical Engineering, The University of Manchester, Manchester, UK
| | - Mark A Hull
- School of Medicine, University of Leeds, Leeds, UK
| | - John Todd
- Research & Development, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | | | - Steve Smith
- Research & Development, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
- Bowel Cancer Screening Hub, NW Bowel Cancer Screening Hub, Hospital of St. Cross, Rugby, UK
| | - Rachel Constable
- Research & Development, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Norman Waugh
- Warwick Clinical Trials Unit, University of Warwick, Coventry, UK
| | - Ramesh P Arasaradnam
- Research & Development, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
- Warwick Medical School, University of Warwick, Coventry, UK
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16
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Ying HQ, Chen W, Xiong CF, Wang Y, Li XJ, Cheng XX. Quantification of fibrinogen-to-pre-albumin ratio provides an integrating parameter for differential diagnosis and risk stratification of early-stage colorectal cancer. Cancer Cell Int 2022; 22:137. [PMID: 35346200 PMCID: PMC8961931 DOI: 10.1186/s12935-022-02532-y] [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: 10/08/2021] [Accepted: 02/24/2022] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Circulating fibrinogen to pre-albumin ratio (FPR) and albumin to fibrinogen ratio (AFR) are effective factors for predicting the prognosis of colorectal cancer (CRC). However, the role of these two ratios in diagnosing early-stage CRC and identifying the stage II CRC subgroup with high relapse risk remains unknown. This study aimed to assess the potential of FPR and AFR in differential diagnosis and risk stratification of early-stage CRC. METHODS A discovery (694 and 512 patients with benign colorectal polyps and stage I-II CRC, respectively) and validation (201 benign colorectal polyps cases and 202 stage I-II CRC individuals) cohorts were enrolled in this study. Receiver operating characteristic curve (ROC), Kaplan-Meier curve, and time-dependent ROC were used to evaluate the diagnostic efficacy of AFR and FPR in the two cohorts and overall population, and the discriminating role of FPR in identifying clinical high-relapse risk patients in comparison with common clinical characteristics in stage II CRC patients. RESULTS The area under the curve (AUC) of the preoperative circulating FPR was higher than that of AFR in the diagnosis of stage I-II CRC from colorectal adenomas and benign colorectal polyps in the discovery and validation cohorts and overall population. Carcinoembryonic antigen (CEA) combined with FPR could effectively discriminate early-stage CRC from colorectal adenomas or benign polyps. Preoperative FPR could effectively distinguish stage II subgroups with high and low relapse risk. It was superior to common clinical characteristics in identifying high-risk surgical patients who could benefit from adjuvant chemotherapy (CT) [time-dependent AUC: 0.637 vs. 0.511, p < 0.001 for predicting recurrence-free survival (RFS); 0.719 vs. 0.501, p < 0.001 for predicting overall survival (OS)]. Furthermore, CT treated stage II patients with FPR > 20 had the highest recurrence (31.16%) and death rates (21.88%), with similar highest recurrence (30.70%) and death (26.82%) rates found in non-CT-treated patients with FPR > 20. Stage II CRC patients with 20 ≥ FPR > 15 could significantly benefit from postoperative CT, as the recurrence (33.30%) and death (35.71%) rates within non-CT treated patients were approximately five times higher than those of the CT-treated cases (6.77% and 7.41% for the recurrence and death rates, respectively). No significant difference in recurrence rate was observed between L-FPR (≤ 15) patients with (10.00%) or without CT (9.76%), indicating that these patients might not require to receive adjuvant CT after curative resection. CONCLUSIONS Preoperative FPR combined with CEA is superior to common tumor biomarkers, FPR, or AFR in distinguishing early-stage CRC from benign colorectal polyps. Circulating FPR can be an effective biomarker for identifying high-risk patients and choosing suitable therapeutics for early-stage CRC.
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Affiliation(s)
- Hou-Qun Ying
- Department of Nuclear Medicine, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Wei Chen
- Department of Nuclear Medicine, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Cui-Fen Xiong
- Jiangxi Medical College, Nanchang University, Nanchang, 330006, People's Republic of China
| | - Yuanyuan Wang
- Department of Laboratory Medicine, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Xiao-Juan Li
- Department of Clinical Laboratory, Kunming Children's Hospital, Kunming, 650103, Yunnan, China
| | - Xue-Xin Cheng
- Biological Resource Center, The Second Affiliated Hospital of Nanchang University, No.1 of Minde Road, Nanchang, 330006, Jiangxi, China.
- School of Public Health, Nanchang University, Nanchang, 330006, People's Republic of China.
- Jiangxi Provincial Key Laboratory of Preventive Medicine, Nanchang University, Nanchang, 330006, People's Republic of China.
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17
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Blad N, Palmqvist R, Karling P. Pre-diagnostic faecal calprotectin levels in patients with colorectal cancer: a retrospective study. BMC Cancer 2022; 22:315. [PMID: 35331198 PMCID: PMC8944005 DOI: 10.1186/s12885-022-09440-4] [Citation(s) in RCA: 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: 08/24/2021] [Accepted: 03/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Faecal calprotectin (FC) is a potential biomarker for colorectal cancer (CRC) screening. There is uncertainty if tumor characteristics are associated with FC levels. We investigated how tumor stage and tumor localization influence the extent of FC levels in patients with CRC in clinical practice. METHODS In two cohorts of patients with CRC, we retrospectively analyzed FC tests (CALPRO®) performed within three months prior to diagnosis. One hundred twenty-four patients with CRC were included (mean age 68 years, 44% women). RESULTS Ninety-eight patients with CRC (79%) had a FC ≥ 50 µg/g. FC correlated positively with tumor stage (UICC based on WHO TNM classification) (rs 0.24; p = 0.007) and with CRP levels (rs 0.31, p = 001), and a negatively with B-haemoglobin (rs -0.21; p = 0.019). The patients with right-sided CRC had significantly more often a FC ≥ 50 µg/g than patients with left-sided CRC (92% vs 74% p = 0.027). In a binary logistic regression analysis, tumor stage III/IV (adjusted OR 3.47; CI 1.27-9.42) and right-sided tumor localization (adjusted OR 3.80; CI 1.01-14.3) were associated with FC ≥ 50 µg/g. Tumor stage III/IV (adjusted OR 2.30; CI 1.04-5.10) and acetylsalicylic use (adjusted OR 3.54; CI 1.03-12.2) were associated with FC ≥ 100 µg/g. In a cox regression analysis, a FC ≥ 100 µg/g was not associated with survival (Hazard OR 0.61; CI 0.24-1.52). CONCLUSIONS Elevated pre-diagnostic FC levels were common in patients with CRC in close proximity to diagnosis. Right-sided localization and tumor stage were significantly associated with a rise in FC levels.
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Affiliation(s)
- Nathalie Blad
- Department of Public Health and Clinical Medicine/Medicine, Umeå University, S90185, Umeå, Sweden
| | - Richard Palmqvist
- Department of Medical Biosciences/ Pathology, Umeå University, Umeå, Sweden
| | - Pontus Karling
- Department of Public Health and Clinical Medicine/Medicine, Umeå University, S90185, Umeå, Sweden.
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18
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Stoltzfus KC, Popalis ML, Reiter PL, Moss JL. Perspectives on self-sampling for cancer screening among rural and urban women: Multilevel factors related to acceptability. J Rural Health 2022; 38:391-397. [PMID: 34002407 PMCID: PMC8599503 DOI: 10.1111/jrh.12590] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
PURPOSE Self-sampling tests may be used to overcome barriers to screening that are more prevalent in rural populations compared to urban populations. This study aims to qualitatively examine the attitudes toward established and novel self-sampling tests for cervical and colorectal cancer among women, comparing themes from rural versus urban areas. METHODS We recruited women (ages 45-65) from 28 counties in Pennsylvania. Four focus groups were conducted with women from metropolitan counties, and 7 focus groups were conducted with women from nonmetropolitan counties. A brief survey was conducted prior to the focus group regarding general health and willingness to complete self-sampling tests for cervical and colorectal cancer. FINDINGS We identified 3 themes about the potential for self-sampling for cancer screening: advantages and disadvantages of self-sampling compared to traditional testing, impact of self-sampling on patient interactions with their health care providers/clinics, and implications for improving/worsening access to quality health care services. We detected differences in responses from rural versus urban participants in the potential impact of self-sampling for cancer screening. CONCLUSIONS There are several barriers and facilitators at the individual, interpersonal, and organizational levels that influence the feasibility of implementing self-sampling for cancer screening in routine clinical practice. Rural participants face unique barriers to cancer screening across all levels. These findings can be used to guide interventions aimed at increasing the use of self-sampling methods.
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Affiliation(s)
- Kelsey C Stoltzfus
- Department of Family and Community Medicine, Penn State College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania, USA
| | - Madyson L Popalis
- Department of Family and Community Medicine, Penn State College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania, USA
| | - Paul L Reiter
- College of Public Health, The Ohio State University, Columbus, Ohio, USA
| | - Jennifer L Moss
- Department of Family and Community Medicine, Penn State College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania, USA
- Department of Public Health Sciences, Penn State College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania, USA
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19
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Comparison of faecal protein biomarkers' diagnostic accuracy for colorectal advanced neoplasms: a systematic review and meta-analysis. Sci Rep 2022; 12:2623. [PMID: 35173276 PMCID: PMC8850428 DOI: 10.1038/s41598-022-06689-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Accepted: 02/03/2022] [Indexed: 11/16/2022] Open
Abstract
Early diagnosis of colorectal advanced neoplasms (ANs), including colorectal cancer (CRC) and advanced adenoma (AA), has a positive effect on the survival rate. As a first attempt, the aim of this meta-analysis was to compare the diagnostic accuracy of faecal protein biomarkers for the detection of colorectal neoplasms with consideration of a wide range of covariates. A systematic literature search was performed up to Jun 10, 2021 on Web of Sciences, Scopus and PubMed. The diagnostic accuracies were calculated using the bivariate/hierarchical random effect model. Biomarkers were determined to be clinically applicable (CA) if they had areas under the curve > 0.70 and positive and negative likelihood ratios > 2 and < 0.5, respectively. A total of 47,059 test results were extracted from 16 immunochemical faecal occult blood test (iFOBT), 26 pyruvate kinase-M2 (PK-M2) and 23 faecal calprotectin (FC) studies. Only iFOBT, PK-M2 and FC for CRC plus iFOBT and PK-M2 for AN were CA. iFOBT had significantly superior accuracy (P = 0.02 versus PK-M2 and P < 0.01 versus FC for CRC; P < 0.01 versus PK-M2 for AN). Regarding covariates, the lateral flow method of PK-M2 measurement increased its accuracy for CRC detection compared to the enzyme-linked immunosorbent assay (P < 0.01). iFOBT is recommended as the most accurate faecal biomarker for CRC and AN diagnosis.
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20
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Ross FA, Park JH, Mansouri D, Little C, Di Rollo DG, Combet E, Van Wyk H, Horgan PG, McMillan DC, Roxburgh CSD. The role of faecal calprotectin in the identification of colorectal neoplasia in patients attending for screening colonoscopy. Colorectal Dis 2022; 24:188-196. [PMID: 34614299 DOI: 10.1111/codi.15942] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 08/12/2021] [Accepted: 09/27/2021] [Indexed: 12/29/2022]
Abstract
AIM Although the relationship between colorectal neoplasia and inflammation is well described, the role of faecal calprotectin (FC) in clinical practice to diagnose or screen patients for colorectal neoplasia is less defined. This prospective study characterizes the relationship between FC and colorectal neoplasia in patients within the faecal occult blood testing (FOBT) positive patients in the Scottish Bowel Screening Programme. METHODS All FOBT positive patients attending for colonoscopy between February 2016 and July 2017 were invited to participate. Patients provided a stool sample for FC before commencing bowel preparation. All demographics and endoscopic findings were collected prospectively. RESULTS In all, 352 patients were included. 210 patients had FC > 50 µg. Colorectal cancer (CRC) patients had a higher median FC (138.5 μg/g, P < 0.05), in comparison to those without CRC, and 13/14 had an FC > 50 µg/g (93%). FC had a high sensitivity (92.8%) and negative predictive value (99.3%) for CRC, but with a low specificity (41.7%) and positive predictive value (6.2%). FC sensitivity increased sequentially as neoplasms progressed from non-advanced to malignant neoplasia (48.6% non-advanced adenoma vs. 92.9% CRC). However, no significant relationship was observed between FC and non-cancer neoplasia. CONCLUSION In an FOBT positive screening population, FC was strongly associated with CRC (sensitivity 92.8%, specificity 41.7% for CRC, at 50 µg/g). However, although sensitive for the detection of CRC, FC failed to show sufficient sensitivity or specificity for the detection of non-cancer neoplasia. Based on these results we cannot recommend routine use of FC in a bowel screening population to detect cancer per se, but it is apparent that, with further optimization, faecal assessments including quantification of haemoglobin and inflammation could form part of a risk assessment tool aimed at refining the selection of patients for colonoscopy in both symptomatic and screening populations.
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Affiliation(s)
- Fiona A Ross
- Academic Unit of Surgery, School of Medicine, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK
| | - James H Park
- Academic Unit of Surgery, School of Medicine, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK
| | - David Mansouri
- Academic Unit of Surgery, School of Medicine, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK
| | - Cariss Little
- Academic Unit of Surgery, School of Medicine, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK
| | - Domenic G Di Rollo
- Academic Unit of Surgery, School of Medicine, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK
| | - Emilie Combet
- Academic Unit of Surgery, School of Medicine, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK
| | - Hester Van Wyk
- Academic Unit of Surgery, School of Medicine, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK
| | - Paul G Horgan
- Academic Unit of Surgery, School of Medicine, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK
| | - Donald C McMillan
- Academic Unit of Surgery, School of Medicine, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK
| | - Campbell S D Roxburgh
- Academic Unit of Surgery, School of Medicine, Glasgow Royal Infirmary, University of Glasgow, Glasgow, UK
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21
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Ranjbar R, Ghasemian M, Maniati M, Hossein Khatami S, Jamali N, Taheri-Anganeh M. Gastrointestinal disorder biomarkers. Clin Chim Acta 2022; 530:13-26. [DOI: 10.1016/j.cca.2022.02.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 02/11/2022] [Accepted: 02/15/2022] [Indexed: 01/19/2023]
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22
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Biomarkers to Detect Early-Stage Colorectal Cancer. Biomedicines 2022; 10:biomedicines10020255. [PMID: 35203465 PMCID: PMC8869393 DOI: 10.3390/biomedicines10020255] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 01/17/2022] [Accepted: 01/20/2022] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer is a leading cause of mortality worldwide. The high incidence and the acceleration of incidence in younger people reinforces the need for better techniques of early detection. The use of noninvasive biomarkers has potential to more accurately inform how patients are prioritised for clinical investigation, which, in turn, may ultimately translate into improved survival for those subsequently found to have curable-stage CRC. This review surveys a wide range of CRC biomarkers that may (alone or in combination) identify symptomatic patients presenting in primary care who should be progressed for clinical investigation.
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23
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Faecal immunochemical test for patients with 'high-risk' bowel symptoms: a large prospective cohort study and updated literature review. Br J Cancer 2021; 126:736-743. [PMID: 34903843 PMCID: PMC8888593 DOI: 10.1038/s41416-021-01653-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 10/21/2021] [Accepted: 11/23/2021] [Indexed: 02/06/2023] Open
Abstract
Background We evaluated whether faecal immunochemical testing (FIT) can rule out colorectal cancer (CRC) among patients presenting with ‘high-risk’ symptoms requiring definitive investigation. Methods Three thousand five hundred and ninety-six symptomatic patients referred to the standard urgent CRC pathway were recruited in a multi-centre observational study. They completed FIT in addition to standard investigations. CRC miss rate (percentage of CRC cases with low quantitative faecal haemoglobin [f-Hb] measurement) and specificity (percentage of patients without cancer with low f-Hb) were calculated. We also provided an updated literature review. Results Ninety patients had CRC. At f-Hb < 10 µg/g, the miss rate was 16.7% (specificity 80.1%). At f-Hb < 4 µg/g, the miss rate was 12.2% (specificity 73%), which became 3.3% if low FIT plus the absence of anaemia and abdominal pain were considered (specificity 51%). Within meta-analyses of 9 UK studies, the pooled miss rate was 7.2% (specificity 74%) for f-Hb < 4 µg/g. Discussion FIT alone as a triage tool would miss an estimated 1 in 8 cases in our study (1 in 14 from meta-analysis), while many people without CRC could avoid investigations. FIT can focus secondary care diagnostic capacity on patients most at risk of CRC, but more work on safety netting is required before incorporating FIT triage into the urgent diagnostic pathway.
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24
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Maclean W, Mackenzie P, Limb C, Zahoor Z, Whyte MB, Rockall T, Benton SC, Jourdan I. Diagnostic accuracy of point of care faecal immunochemical testing using a portable high-speed quantitative analyser for diagnosis in 2-week wait patients. Colorectal Dis 2021; 23:2376-2386. [PMID: 34157205 DOI: 10.1111/codi.15780] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 05/26/2021] [Accepted: 06/16/2021] [Indexed: 02/08/2023]
Abstract
AIM Laboratory-based faecal immunochemical testing (FIT) is the gold standard for detecting the presence of blood in the stool. The aim was to perform a diagnostic accuracy study to confirm if a point of care (POC) analyser for FIT could be safely used as an adjunct in the triage and management of 2-week wait (TWW) colorectal patients. METHODS The Point of Care Faecal Immunochemical Testing (POC FIT) prospective observational cohort study was designed for TWW patients at a regional referral centre. Between July 2019 and March 2020, patients were invited to perform and bring a FIT sample to clinic. FIT was completed within the clinic appointment using a POC quantitative analyser that has a 2-min processing time (QuikRead go®). Patients and clinicians were blinded to results within the clinic appointment. The results were compared with subsequent diagnostic outcomes. Faecal haemoglobin of <10 µg haemoglobin/g of faeces was considered a negative result. Sensitivities for colorectal cancer (CRC) and combined serious bowel disease (SBD) were calculated using this pre-determined cut-off. RESULTS A total of 553 patients were included for analytical comparison with diagnostic outcomes. There were 14 (2.5%) patients with CRC and 52 (9.4%) with SBD. The sensitivities for CRC and SBD were 92.9% (95% CI 68.5%-98.7%) and 76.9% (95% CI 63.9%-86.3%) respectively. 379 (68.5%) patients had a negative FIT result (negative predictive value for CRC was 99.7%). CONCLUSIONS This POC FIT device is a useful adjunct to better manage TWW patients. The high observed sensitivity for CRC offers opportunities, within a single consultation, for improved triage and rationalization of investigation for those with bowel symptoms.
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Affiliation(s)
- William Maclean
- General Surgery at Royal Surrey NHS Foundation Trust, Guildford, UK
| | - Paul Mackenzie
- General Surgery at Royal Surrey NHS Foundation Trust, Guildford, UK
| | - Chris Limb
- General Surgery at Royal Surrey NHS Foundation Trust, Guildford, UK
| | - Zahida Zahoor
- Bowel Cancer Screening Hub at Royal Surrey NHS Foundation Trust, Guildford, UK
| | - Martin B Whyte
- Metabolic Medicine at University of Surrey, Guildford, UK
| | - Timothy Rockall
- General Surgery at Royal Surrey NHS Foundation Trust, Guildford, UK
| | - Sally C Benton
- Bowel Cancer Screening Hub at Royal Surrey NHS Foundation Trust, Guildford, UK
| | - Iain Jourdan
- General Surgery at Royal Surrey NHS Foundation Trust, Guildford, UK
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25
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Tyagi H, Daulton E, Bannaga AS, Arasaradnam RP, Covington JA. Non-Invasive Detection and Staging of Colorectal Cancer Using a Portable Electronic Nose. SENSORS (BASEL, SWITZERLAND) 2021; 21:5440. [PMID: 34450881 PMCID: PMC8398649 DOI: 10.3390/s21165440] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 07/30/2021] [Accepted: 07/30/2021] [Indexed: 12/24/2022]
Abstract
Electronic noses (e-nose) offer potential for the detection of cancer in its early stages. The ability to analyse samples in real time, at a low cost, applying easy-to-use and portable equipment, gives e-noses advantages over other technologies, such as Gas Chromatography-Mass Spectrometry (GC-MS). For diseases such as cancer with a high mortality, a technology that can provide fast results for use in routine clinical applications is important. Colorectal cancer (CRC) is among the highest occurring cancers and has high mortality rates, if diagnosed late. In our study, we investigated the use of portable electronic nose (PEN3), with further analysis using GC-TOF-MS, for the analysis of gases and volatile organic compounds (VOCs) to profile the urinary metabolome of colorectal cancer. We also compared the different cancer stages with non-cancers using the PEN3 and GC-TOF-MS. Results obtained from PEN3, and GC-TOF-MS demonstrated high accuracy for the separation of CRC and non-cancer. PEN3 separated CRC from non-cancerous group with 0.81 AUC (Area Under the Curve). We used data from GC-TOF-MS to obtain a VOC profile for CRC, which identified 23 potential biomarker VOCs for CRC. Thus, the PEN3 and GC-TOF-MS were found to successfully separate the cancer group from the non-cancer group.
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Affiliation(s)
- Heena Tyagi
- School of Engineering, University of Warwick, Coventry CV4 7AL, UK; (H.T.); (E.D.)
| | - Emma Daulton
- School of Engineering, University of Warwick, Coventry CV4 7AL, UK; (H.T.); (E.D.)
| | - Ayman S. Bannaga
- Department of Gastroenterology, University Hospital Coventry & Warwickshire, Coventry CV2 2DX, UK; (A.S.B.); (R.P.A.)
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
| | - Ramesh P. Arasaradnam
- Department of Gastroenterology, University Hospital Coventry & Warwickshire, Coventry CV2 2DX, UK; (A.S.B.); (R.P.A.)
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- School of Health Sciences, Coventry University, Coventry CV1 5FB, UK
- Leicester Cancer Centre, University of Leicester, Leicester LE1 7RH, UK
| | - James A. Covington
- School of Engineering, University of Warwick, Coventry CV4 7AL, UK; (H.T.); (E.D.)
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26
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Turvill JL, Turnock D, Cottingham D, Haritakis M, Jeffery L, Girdwood A, Hearfield T, Mitchell A, Keding A. The Fast Track FIT study: diagnostic accuracy of faecal immunochemical test for haemoglobin in patients with suspected colorectal cancer. Br J Gen Pract 2021; 71:e643-e651. [PMID: 33798091 PMCID: PMC8279659 DOI: 10.3399/bjgp.2020.1098] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 03/24/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The faecal immunochemical test (FIT) is now available to support clinicians in the assessment of patients at low risk of colorectal cancer (CRC) and within the bowel cancer screening programme. AIM To determine the diagnostic accuracy of FIT for CRC and clinically significant disease in patients referred as they were judged by their GP to fulfil National Institute for Health and Care Excellence guideline 12 (NG12) criteria for suspected CRC. DESIGN AND SETTING Patients referred from primary care with suspected CRC, meeting NG12 criteria, to 12 secondary care providers in Yorkshire and Humber were asked to complete a FIT before investigation. METHOD The diagnostic accuracy of FIT based on final diagnosis was evaluated using receiver operating characteristics analysis. This permitted a statistically optimal cut-off value for FIT to be determined based on the maximisation of sensitivity and specificity. Clinicians and patients were blinded to the FIT results. RESULTS In total, 5040 patients were fully evaluated and CRC was detected in 151 (3.0%). An optimal cut-off value of 19 µg Hb/g faeces for CRC was determined, giving a sensitivity of 85.4% (95% confidence interval [CI] = 78.8% to 90.6%) and specificity of 85.2% (95% CI = 84.1% to 86.2%). The negative predictive value at this cut-off value was 99.5% (95% CI = 99.2% to 99.7%) and the positive predictive value 15.1% (95% CI = 12.8% to 17.7%). Sensitivity and specificity of FIT for CRC and significant premalignant polyps at this cut-off value were 62.9% (95% CI = 57.5% to 68.0%) and 86.4% (95% CI = 85.4% to 87.4%), respectively; and when including all organic enteric disease were 35.7% (95% CI = 32.9% to 38.5%) and 88.6% (95% CI = 87.5% to 89.6%), respectively. CONCLUSION FIT used in patients fulfilling NG12 criteria should allow for a more personalised CRC risk assessment. FIT should permit effective, patient-centred decision-making to inform the need for, type, and timing of further investigation.
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Affiliation(s)
- James L Turvill
- Department of Gastroenterology, York and Scarborough Teaching Hospitals NHS Foundation Trust, York
| | - Daniel Turnock
- Department of Gastroenterology, York and Scarborough Teaching Hospitals NHS Foundation Trust, York
| | - Dan Cottingham
- Macmillan GP Cancer and End of Life lead, Vale of York Clinical Commissioning Group, West Offices Station Rise, York
| | - Monica Haritakis
- Department of Research and Development, York and Scarborough Teaching Hospitals NHS Foundation Trust, York
| | - Laura Jeffery
- Department of Research and Development, York and Scarborough Teaching Hospitals NHS Foundation Trust, York
| | - Annabelle Girdwood
- Department of Research and Development, York and Scarborough Teaching Hospitals NHS Foundation Trust, York
| | - Tom Hearfield
- Department of Research and Development, York and Scarborough Teaching Hospitals NHS Foundation Trust, York
| | - Alex Mitchell
- Department of Health Sciences, Faculty of Sciences, University of York, York
| | - Ada Keding
- Department of Health Sciences, Faculty of Sciences, University of York, York
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27
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Chandrapalan S, Hee SW, Widlak MM, Farrugia A, Alam MT, Smith S, Arasaradnam RP. Performance of the faecal immunochemical test for the detection of colorectal neoplasms and the role of proton pump inhibitors in their diagnostic accuracy. Colorectal Dis 2021; 23:1649-1657. [PMID: 33991166 DOI: 10.1111/codi.15735] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 04/19/2021] [Accepted: 05/08/2021] [Indexed: 02/06/2023]
Abstract
AIM The faecal immunochemical test (FIT) is currently utilized in both symptomatic and screening populations, but little is known about factors that affect its performance. For example, proton pump inhibitor (PPI) therapy has been purported to increase false negative rates. This has significant implications given the extent of PPI prescriptions. The aim of this work was to evaluate the performance of the FIT for the detection of colorectal neoplasms and the impact of PPI therapy on its diagnostic accuracy. METHOD Symptomatic patients referred on the suspected cancer pathway and those on polyp surveillance between 2015 and 2019 were approached to participate. Estimates of the accuracy of FIT at different cut-off levels in diagnosing colorectal neoplasms were made. Logistic regression was used to assess the effect of PPIs on the FIT results. RESULTS A total of 667 participants were eligible for the final analysis. At a cut-off of 10 μg/g faeces, the overall sensitivity and specificity of FIT for the detection of colorectal cancer (CRC) was 0.85 (95% CI 0.71-0.94) and 0.81 (95% CI 0.78-0.84), respectively. For the detection of advanced neoplasia, the sensitivity was 0.70 (95% CI 0.58-0.79) and the specificity was 0.83 (95% CI 0.80-0.86). At higher thresholds, the sensitivity steadily declined whilst specificity increased. PPI therapy did not have a significant effect on performance of the FIT. CONCLUSION FIT is a good rule-out test for the detection of CRC and advanced neoplasia at lower thresholds. PPI therapy does not appear to have an effect on its diagnostic performance.
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Affiliation(s)
- Subashini Chandrapalan
- Warwick Medical School, University of Warwick, Coventry, UK.,University Hospital of Coventry and Warwickshire, Coventry, UK
| | - Siew Wan Hee
- Warwick Medical School, University of Warwick, Coventry, UK
| | - Monika M Widlak
- Warwick Medical School, University of Warwick, Coventry, UK.,University Hospital of Coventry and Warwickshire, Coventry, UK
| | - Alexia Farrugia
- Warwick Medical School, University of Warwick, Coventry, UK.,University Hospital of Coventry and Warwickshire, Coventry, UK
| | - Mohammed T Alam
- Department of Biology, College of Science, United Arab Emirates University, Al-Ain, UAE
| | - Steve Smith
- Midlands and North West Bowel Cancer Screening Hub, University Hospital of Coventry and Warwickshire, Coventry, UK
| | - Ramesh P Arasaradnam
- Warwick Medical School, University of Warwick, Coventry, UK.,University Hospital of Coventry and Warwickshire, Coventry, UK.,Health, Biological and Experimental Sciences, University of Coventry, Coventry, UK.,School of Health Sciences, University of Leicester, Leicester, UK
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28
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Chandrapalan S, Bosch S, Cubiella J, Guardiola J, Kimani P, Mulder C, Persaud K, de Meij TGJ, Altomare DF, Brenner H, de Boer NKH, Ricciardiello L, Arasaradnam RP. Systematic review with meta-analysis: volatile organic compound analysis to improve faecal immunochemical testing in the detection of colorectal cancer. Aliment Pharmacol Ther 2021; 54:14-23. [PMID: 34004036 DOI: 10.1111/apt.16405] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 03/20/2021] [Accepted: 04/24/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND Faecal immunochemical test (FIT) is emerging as a valid test to rule-out the presence of colorectal cancer (CRC). However, the accuracy of FIT is dependent on the cut-off applied. An additional low-cost test could improve further detection of CRC. AIMS To evaluate the efficacy of combined FIT and volatile organic compounds (VOC) in the detection of CRC within symptomatic populations. METHODS Systematic reviews on the diagnostic accuracy of FIT and VOC, for the detection of CRC, were updated. Meta-analyses were performed adopting a bivariate model for sensitivity and specificity. Clinical utility of combined FIT and VOC was estimated using Fagan's nomogram. Post-test probability of FIT negatives was used as a pre-test probability for VOC. RESULTS The pooled sensitivity and specificity of FIT at 10 µg/g faeces, for the detection of CRC, were 0.914 (95% confidence interval [CI] = 0.894-0.936) and 0.783 (CI = 0.850-0.696), respectively. For VOC, the sensitivity was 0.837 (CI = 0.781-0.881) and the specificity was 0.803 (CI = 0.870-0.712). The area under the curve for FIT and VOC were 0.926 and 0.885, respectively. In a population with 5% CRC prevalence, the estimated probability of having CRC following a negative FIT was 0.5% and following both negative FIT and VOC was 0.1%. CONCLUSIONS In a FIT-negative symptomatic population, VOC can be a good test to rule-out the presence of CRC. The estimated probability reduction by 0.4% when both tests being negative offers adequate safety netting in primary care for the exclusion of CRC. The number needed to colonoscope to identify one CRC is eight if either FIT or VOC positive. Cost-effectiveness and clinical accuracy of this approach will need further evaluation.
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Hicks G, D'Souza N, Georgiou Delisle T, Chen M, Benton SC, Abulafi M. Using the faecal immunochemical test in patients with rectal bleeding: evidence from the NICE FIT study. Colorectal Dis 2021; 23:1630-1638. [PMID: 33605522 DOI: 10.1111/codi.15593] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 02/10/2021] [Accepted: 02/11/2021] [Indexed: 12/13/2022]
Abstract
AIM The aim of this work was to investigate whether the faecal immunochemical test (FIT) could safely rule out colorectal cancer (CRC) in patients with rectal bleeding (RB). METHOD This was a multicentre, double-blinded diagnostic accuracy study in 50 National Health Service hospitals. Patients referred from primary care with suspected CRC on an urgent 2-week-wait pathway were asked to perform a FIT prior to colonoscopy. The primary outcome measure was the sensitivity of the FIT for CRC in patients with RB versus nonrectal bleeding symptoms (NRB). The secondary outcome measures included the diagnostic accuracy of the FIT for CRC and other serious bowel disease. RESULTS Of 9822 patients included in the study, 3143 (32.0%) were referred with RB. CRC was present in 4.7% of patients with RB versus 2.7% of patients with NRB (p < 0.05). Faecal haemoglobin (f-Hb) was detectable (>2 µg/g) in 44.1% of patients with RB and 33.9% with NRB (p < 0.05). In RB patients, CRC was present in 10.4% when f-Hb was >2 µg/g compared with 0.1% when f-Hb was not detected. Flexible sigmoidoscopy in this group would further reduce the risk of CRC to 0.03%. The sensitivity of the FIT for CRC in RB versus NRB groups was 98.6% (95% CI 95.2%-99.8%) vs 95.6% (91.5%-98.1%) for f-Hb >2 µg/g and 96.6% (92.2%-98.9%) vs 86.3 (80.4%-90.9%) for f-Hb >10 µg/g. CONCLUSION Faecal haemoglobin is not always detectable in patients with RB; 56% of patients had undetectable f-Hb (<2 µg/g) and CRC was present in 0.1%. The high sensitivity of the FIT can be used to rule out CRC in patients with RB and triage them more appropriately for investigation.
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Affiliation(s)
| | - Nigel D'Souza
- Croydon University Hospital, Croydon, UK.,University Hospital Southampton NHS Foundation Trust, Southampton, UK.,Imperial College London, London, UK
| | | | - Michelle Chen
- RM Partners, The West London Cancer Alliance, London, UK
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Hijos-Mallada G, Lué A, Velamazan R, Saura N, Abril C, Lorenzo M, Navarro M, Chueca E, Arechavaleta S, Gomollón F, Lanas Á, Sostres C. The Addition of Other Fecal Biomarkers Does Not Improve the Diagnostic Accuracy of Immunochemical Fecal Occult Blood Test Alone in a Colorrectal Cancer Screening Cohort. Front Med (Lausanne) 2021; 8:665786. [PMID: 34150803 PMCID: PMC8212973 DOI: 10.3389/fmed.2021.665786] [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: 02/08/2021] [Accepted: 05/11/2021] [Indexed: 01/13/2023] Open
Abstract
Background: Screening with fecal occult blood test reduces colorectal cancer (CRC) incidence and mortality, and is currently implemented in most countries. However, around 40% of screening colonoscopies are normal. Thus, strategies to avoid these colonoscopies are highly necessary. Adding other fecal biomarkers, such as fecal calprotectin (FC), lactoferrin, and transferrin may be useful, but evidence is scarce. Aims: To evaluate the diagnostic accuracy of fecal occult blood immunochemical test (FIT), FC, and a one-step combo card test for the simultaneous semi-qualitative detection of human hemoglobin (hHb), transferrin (hTf), calprotectin (hCp) and lactoferrin (hLf) in a CRC screening program population. Methods: Single-center, prospective observational study, enrolling patients included in a CRC screening program, referred for a colonoscopy due to a positive FIT test. Participants collected a stool sample prior to bowel preparation, and FIT, FC and the combo semi-qualitative tests were performed on the sample. Sensitivity, specificity, positive and negative predictive values and area under receiver operator curve (AUC) for diagnosis of advanced neoplasia, advanced adenoma and CRC were estimated for each biomarker and their combinations. The primary endpoint of the study was to assess whether these biomarkers could improve the diagnostic accuracy of FIT alone. Results: 336 consecutive patients (64% males) were recruited. Advanced neoplasia was found in 129/336 (38.4%) patients, and of these, 22/336 (6.5%) were diagnosed of CRC. 153/336 (45.5%) colonoscopies were completely normal. The AUC for the diagnosis of advanced neoplasia were 0.725 (95%CI 0.665–0.784) for FIT, 0.477 (95%CI 0.413–0.541) for FC and 0.732 (95%CI 0.674–0.791) for the combination of both (FIT + FC) quantitative tests. The AUCs for the combo test were 0.70 (95%CI 0.641–0.760) for hHb, 0.625 (95%CI 0.562–0.698) for hTf, 0.532 (95%CI 0.469–0.595) for hCp, 0.531 (95%CI 0.466–0.595 ) for hLf and 0.681 (95%CI 0.620–0.741) for the combination of the four biomarkers. Conclusion: In average-risk population, FIT appears to be the best fecal marker for the diagnosis of CRC and advanced adenoma. None of the other biomarkers explored or their combinations provided a better diagnostic accuracy. Only hTF showed an acceptable diagnostic accuracy. FC and hLF were not useful in this setting.
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Affiliation(s)
- Gonzalo Hijos-Mallada
- Digestive Diseases Service, University Clinic Hospital, Zaragoza, Spain.,Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain
| | - Alberto Lué
- Digestive Diseases Service, University Clinic Hospital, Zaragoza, Spain.,Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain
| | - Raul Velamazan
- Digestive Diseases Service, University Clinic Hospital, Zaragoza, Spain.,Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain
| | - Nuria Saura
- Digestive Diseases Service, University Clinic Hospital, Zaragoza, Spain.,Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain
| | | | | | - Mercedes Navarro
- Digestive Diseases Service, University Clinic Hospital, Zaragoza, Spain.,Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain
| | - Eduardo Chueca
- Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.,CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), Zaragoza, Spain
| | - Samantha Arechavaleta
- Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.,CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), Zaragoza, Spain
| | - Fernando Gomollón
- Digestive Diseases Service, University Clinic Hospital, Zaragoza, Spain.,Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.,University of Zaragoza, Zaragoza, Spain.,CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), Zaragoza, Spain
| | - Ángel Lanas
- Digestive Diseases Service, University Clinic Hospital, Zaragoza, Spain.,Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.,University of Zaragoza, Zaragoza, Spain.,CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), Zaragoza, Spain
| | - Carlos Sostres
- Digestive Diseases Service, University Clinic Hospital, Zaragoza, Spain.,Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.,University of Zaragoza, Zaragoza, Spain.,CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), Zaragoza, Spain
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Jiwa N, Takats Z, Leff DR, Sutton C. Breast health screening: a UK-wide questionnaire. BMJ Nutr Prev Health 2021; 4:206-212. [PMID: 34308128 PMCID: PMC8258049 DOI: 10.1136/bmjnph-2021-000266] [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: 03/02/2021] [Revised: 04/12/2021] [Accepted: 04/15/2021] [Indexed: 11/04/2022] Open
Abstract
Background Currently, there is an unmet clinical need in identifying and screening women at high risk of breast cancer, where tumours are often aggressive and treatment intervention is too late to prevent metastasis, recurrence and mortality. This has been brought into sharp focus by the SARS-CoV-2 global pandemic, constantly changing hospital policies and surgical guidelines in reducing access to established screening and treatment regimens. Nipple aspirate fluid (NAF), is thought to provide a unique window into the biological processes occurring within the breast, particularly in the context of a developing neoplasm. Evaluation of NAF in asymptomatic women, for novel chemical biomarkers of either early disease and/or cancer risk offers tremendous promise as a tool to facilitate early detection and to supplement screening. However, it is acceptability as a method of collection and screening by women is critical and yet unknown. A breast health questionnaire was disseminated to women through breast cancer charities, patient support groups and social media platforms, with the aim of collecting opinions on the acceptability of use of NAF as a potential screening tool. Method Following ethical approval a questionnaire was prepared using online surveys consisting of four parts: (a) introduction on breast health screening in the UK, (b) core demographic data, (c) questions regarding screening and the acceptability of using NAF and (d) opinions about the process of collecting and using nipple fluid for screening. The voluntary and anonymous questionnaire was disseminated through social media, professional networks, charity websites and by individuals between October 2019 and December 2020. Survey responses were collected electronically, and the data analysed using online surveys statistical tools. Results A total of 3178 women completed the questionnaire (65.9% Caucasian, 27.7% Asian/British Asian, 0.6% black and 5.0% other). Of these, 2650 women (83.4%) had no prior knowledge of NAF and 89.4% were unaware that NAF can be expressed in up to 90% of all women. Concerning their risk of breast cancer, 89.8% of women were keen to know their future risk of breast cancer, 8.5% were unsure whether they wanted to know their risk and a further, 1.6% did not want to know. Regarding screening, 944 women (29.8%) were unaware of the lack of routine National Health Service Breast Screening for those under the age of 47 years. Furthermore, 53.0% of women were unaware that mammographic screening is affected by breast density. In terms of the acceptability of home testing for breast health, 92.0% were keen to undergo a home test. Both 79.7% and 70.9% stated they would consider hand massage and a breast pump to acquire nipple fluid samples, respectively. A further 48.6% of women would consider the use of a hormonal nasal spray for the same purpose. However, with regards to acquiring results from NAF testing, 42.6% of women would prefer to receive results at home and 34.2% in a medical facility. Finally, 91.6% of women believed that breast health should be incorporated as part of school education curriculum. Conclusion Public awareness regarding breast screening protocols and limitations of mammography could be improved. Many women were unaware that NAF might be a useful biofluid for future risk prediction, and yet the concept of self-testing of nipple fluid, with either hand massage or a breast pump was well received. Efforts should be made to increase awareness of the benefits of alternative and supplementary tests, especially in the context of high-risk individuals and younger patients.
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Affiliation(s)
- Natasha Jiwa
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Zoltan Takats
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Daniel R Leff
- Department of Surgery and Cancer, Imperial College London, London, UK.,Department of Breast Surgery, Imperial College Healthcare NHS Trust, London, UK
| | - Christopher Sutton
- Department of Chemistry and Biosciences, University of Bradford, Bradford, UK
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Bailey JA, Khawaja A, Andrews H, Weller J, Chapman C, Morling JR, Oliver S, Castle S, Simpson JA, Humes DJ, Banerjea A. GP access to FIT increases the proportion of colorectal cancers detected on urgent pathways in symptomatic patients in Nottingham. Surgeon 2021; 19:93-102. [PMID: 32327303 DOI: 10.1016/j.surge.2020.03.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 03/13/2020] [Indexed: 12/27/2022]
Abstract
OBJECTIVE Service evaluation of GP access to Faecal Immunochemical Test (FIT) for colorectal cancer (CRC) detection in Nottinghamshire and use of FIT for "rule out", "rule in" and "first test selection". DESIGN Retrospective audit of FIT results, CRC outcomes and resource utilisation before and after introduction of FIT in Primary Care in November 2017. Data from the new pathway up to December 2018 was compared with previous experience. RESULTS Between November 2017 and December 2018, 6747 GP FIT test requests yielded 5733 FIT results, of which 4082 (71.2%) were <4.0 μg Hb/g faeces, 579 (10.1%) were 4.0-9.9 μg Hb/g faeces, 836 (14.6%) were 10.0-149.9 μg Hb/g faeces, and 236 (4.1%) were ≥150.0 μg Hb/g faeces. The proportion of "rule out" results <4.0 μg Hb/g faeces was significantly higher than in the Getting FIT cohort (71.2% vs 60.4%, Chi squared 42.8, p < 0.0001) and the proportion of "rule in" results ≥150.0 μg Hb/g faeces was significantly lower (4.1% vs 8.1%, Chi squared 27.3,P < 0.0001). There was a 33% rise in urgent referrals across Nottingham overall during the evaluation period. 2 CRC diagnoses were made in 4082 patients who had FIT<4.0 μg Hb/g faeces. 58.4% of new CRC diagnoses associated with a positive FIT were early stage cancers (Stage I and II). The proportion of all CRC diagnoses that follow an urgent referral s rose after introduction of FIT. CONCLUSIONS FIT allows GP's to select a more appropriate cohort for urgent investigation without a large number of missed diagnoses. FIT appears to promise a "stage migration" effect which may ultimately improve CRC outcomes.
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Affiliation(s)
- J A Bailey
- Nottingham Colorectal Service, E Floor West Block, QMC Campus, Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK.
| | - A Khawaja
- Nottingham Colorectal Service, E Floor West Block, QMC Campus, Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK
| | - H Andrews
- Nottingham Colorectal Service, E Floor West Block, QMC Campus, Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK
| | - J Weller
- Nottingham Colorectal Service, E Floor West Block, QMC Campus, Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK
| | - C Chapman
- Eastern Hub, Bowel Cancer Screening Programme, A Floor West Block, QMC Campus, Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK
| | - J R Morling
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, NG7 2UH, UK; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Clinical Sciences Building 2, City Hospital, Nottingham, NG5 1PB, UK
| | - S Oliver
- Nottingham City Clinical Commissioning Group, Nottingham, UK
| | - S Castle
- Nottingham City Clinical Commissioning Group, Nottingham, UK
| | - J A Simpson
- Nottingham Colorectal Service, E Floor West Block, QMC Campus, Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK
| | - D J Humes
- Nottingham Colorectal Service, E Floor West Block, QMC Campus, Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, NG7 2UH, UK; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Clinical Sciences Building 2, City Hospital, Nottingham, NG5 1PB, UK
| | - A Banerjea
- Nottingham Colorectal Service, E Floor West Block, QMC Campus, Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK
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D'Souza N, Delisle TG, Chen M, Benton SC, Abulafi M. Faecal immunochemical testing in symptomatic patients to prioritize investigation: diagnostic accuracy from NICE FIT Study. Br J Surg 2021; 108:804-810. [PMID: 33755051 DOI: 10.1093/bjs/znaa132] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 10/01/2020] [Accepted: 11/15/2020] [Indexed: 11/13/2022]
Abstract
BACKGROUND This study investigated whether a quantitative faecal immunochemical test (FIT) could be used to select patients with either high- or low-risk symptoms of colorectal cancer for urgent investigation. METHODS A double-blinded diagnostic accuracy study was conducted in 50 hospitals in England between October 2017 and December 2019. Patients were eligible for inclusion if they had been referred to secondary care with suspected colorectal cancer symptoms meeting national criteria for urgent referral and triaged to investigation with colonoscopy. RESULTS The study included 9822 patients, of whom 7194 (73.2 per cent) had high-risk symptoms, 1994 (20.3 per cent) low-risk symptoms, and 634 (6.5 per cent) had other symptoms warranting urgent referral. In patients with high-risk symptoms, the sensitivity of FIT for colorectal cancer at cut-off values of 2 and 10 μg haemoglobin per g faeces was 97.7 (95 per cent c.i. 95.0 to 99.1) and 92.2 (88.2 to 95.2) per cent respectively, compared with 94.3 (84.3 to 98.8) and 86.8 (74.7 to 94.5) per cent in patients with low-risk symptoms at the same cut-off points. At cut-off values of 2, 10, and 150 μg/g, the positive predictive value for colorectal cancer was 8.9, 16.2, and 30.5 per cent respectively for those with high-risk symptoms, and 8.4, 16.9, and 35.5 per cent for those with low-risk symptoms. CONCLUSION FIT safely selects patients with high or low risk symptoms of colorectal cancer for investigation.
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Affiliation(s)
- N D'Souza
- Department of Colorectal Surgery, Croydon University Hospital, Croydon, UK.,Department of Colorectal Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK.,Department of Surgery and Cancer, Imperial College London, London, UK
| | - T Georgiou Delisle
- Department of Colorectal Surgery, Croydon University Hospital, Croydon, UK.,School of Public Health, Imperial College London, London, UK
| | - M Chen
- Department of Research and Development, RM Partners, West London Cancer Alliance, London, UK
| | - S C Benton
- Department of Biochemistry, Royal Surrey County Hospital, Guildford, UK
| | - M Abulafi
- Department of Colorectal Surgery, Croydon University Hospital, Croydon, UK
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Bailey JA, Weller J, Chapman CJ, Ford A, Hardy K, Oliver S, Morling JR, Simpson JA, Humes DJ, Banerjea A. Faecal immunochemical testing and blood tests for prioritization of urgent colorectal cancer referrals in symptomatic patients: a 2-year evaluation. BJS Open 2021; 5:6162967. [PMID: 33693553 PMCID: PMC7947575 DOI: 10.1093/bjsopen/zraa056] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 11/15/2020] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND A novel pathway incorporating faecal immunochemical testing (FIT) for rapid colorectal cancer diagnosis (RCCD) was introduced in 2017. This paper reports on the service evaluation after 2 years of pathway implementation. METHODS The RCCD protocol was based on FIT, blood results and symptoms to stratify adult patients in primary care. Two-week-wait (2WW) investigation was indicated for patients with rectal bleeding, rectal mass and faecal haemoglobin (fHb) level of 10 µg Hb/g faeces or above or 4 µg Hb/g faeces or more in the presence of anaemia, low ferritin or thrombocytosis, in all other symptom groups. Patients with 100 µg Hb/g faeces or above had expedited investigation . A retrospective audit of colorectal cancer detected between 2017 and 2019 was conducted, fHb thresholds were reviewed and critically assessed for cancer diagnoses. RESULTS In 2 years, 14788 FIT tests were dispatched with 13361 (90.4 per cent) completed returns. Overall, fHb was less than 4 µg Hb/g faeces in 9208 results (68.9 per cent), 4-9.9 µg Hb/g in 1583 (11.8 per cent), 10-99.9 µg Hb/g in 1850 (13.8 per cent) and 100 µg Hb/g faeces or above in 720 (5.4 per cent). During follow-up (median 10.4 months), 227 colorectal cancers were diagnosed. The cancer detection rate was 0.1 per cent in patients with fHb below 4 µg Hb/g faeces, 0.6 per cent in those with fHb 4-9.9 µg Hb/g faeces, 3.3 per cent for fHb 10-99.9 µg Hb/g faeces and 20.7 per cent for fHb 100 µg Hb/g faeces or above. The detection rate in the cohort with 10-19.9 µg Hb/g faeces was 1.4 per cent, below the National Institute for Health and Care Excellence threshold for urgent referral. The colorectal cancer rate in patients with fHb below 20 µg Hb/g faeces was less than 0.3 per cent. CONCLUSION Use of FIT to "rule out" urgent referral from primary care misses a small number of cases. The threshold for referral may be adjusted with blood results to improve stratification .
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Affiliation(s)
- J A Bailey
- Nottingham Colorectal Service, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - J Weller
- Nottingham Colorectal Service, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - C J Chapman
- Eastern Hub, Bowel Cancer Screening Programme, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - A Ford
- Eastern Hub, Bowel Cancer Screening Programme, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - K Hardy
- Eastern Hub, Bowel Cancer Screening Programme, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - S Oliver
- Nottingham City Clinical Commissioning Group, Nottingham,UK
| | - J R Morling
- National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK,Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK
| | - J A Simpson
- Eastern Hub, Bowel Cancer Screening Programme, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - D J Humes
- Nottingham Colorectal Service, Nottingham University Hospitals NHS Trust, Nottingham, UK,National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK,Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK,Correspondence to: Nottingham Colorectal Service, E Floor West Block, Queen’s Medical Centre Campus, Nottingham University Hospitals NHS Trust, Derby Road, Nottingham NG7 2UH, UK (e-mail: )
| | - A Banerjea
- Nottingham Colorectal Service, Nottingham University Hospitals NHS Trust, Nottingham, UK
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The Multiomics Analyses of Fecal Matrix and Its Significance to Coeliac Disease Gut Profiling. Int J Mol Sci 2021; 22:ijms22041965. [PMID: 33671197 PMCID: PMC7922330 DOI: 10.3390/ijms22041965] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 02/08/2021] [Accepted: 02/11/2021] [Indexed: 12/15/2022] Open
Abstract
Gastrointestinal (GIT) diseases have risen globally in recent years, and early detection of the host’s gut microbiota, typically through fecal material, has become a crucial component for rapid diagnosis of such diseases. Human fecal material is a complex substance composed of undigested macromolecules and particles, and the processing of such matter is a challenge due to the unstable nature of its products and the complexity of the matrix. The identification of these products can be used as an indication for present and future diseases; however, many researchers focus on one variable or marker looking for specific biomarkers of disease. Therefore, the combination of genomics, transcriptomics, proteomics and metabonomics can give a detailed and complete insight into the gut environment. The proper sample collection, sample preparation and accurate analytical methods play a crucial role in generating precise microbial data and hypotheses in gut microbiome research, as well as multivariate data analysis in determining the gut microbiome functionality in regard to diseases. This review summarizes fecal sample protocols involved in profiling coeliac disease.
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Mowat C, Digby J, Strachan JA, McCann RK, Carey FA, Fraser CG, Steele RJ. Faecal haemoglobin concentration thresholds for reassurance and urgent investigation for colorectal cancer based on a faecal immunochemical test in symptomatic patients in primary care. Ann Clin Biochem 2021; 58:211-219. [PMID: 33334134 PMCID: PMC8114428 DOI: 10.1177/0004563220985547] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Background Faecal haemoglobin concentration (f-Hb), estimated using a faecal immunochemical test, can be safely implemented in primary care to assess risk of colorectal cancer (CRC). Clinical outcomes of patients presenting with symptoms of lower gastrointestinal disease were examined using an extensive range of f-Hb thresholds to decide on reassurance or referral for further investigation. Methods All patients who attended primary care and submitted a single faecal specimen faecal immunochemical test in the first year of the routine service had f-Hb estimated using HM-JACKarc: f-Hb thresholds from <2 to ≥ 400 µg Hb/g faeces (µg/g) were examined. Results Low f-Hb thresholds of <2, <7, <10 and <20 µg/g gave respective CRC risks of 0.1, 0.3, 0.3 and 0.4%, numbers needed to scope for one CRC of 871, 335, 300 and 249, and ‘false negative’ rates of 2.9, 11.4, 13.3 and 17.1%. With thresholds of <2, <7, <10 and <20 µg/g, 48.6, 74.6, 78.1 and 83.2% respectively of symptomatic patients could be managed without further investigation. With reassurance thresholds of <2 µg/g, <7 µg/g and <10 µg/g, the thresholds for referral for urgent investigation would be >400 µg/g, ≥200 µg/g and ≥100 µg/g. However, patients with a f-Hb concentration of <10 or <20 µg/g with iron deficiency anaemia, or with severe or persistent symptoms, should not be denied further investigation. Conclusions In primary care, f-Hb, in conjunction with clinical assessment, can safely and objectively determine individual risk of CRC and decide on simple reassurance or urgent, or routine referral.
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Affiliation(s)
- Craig Mowat
- Department of Gastroenterology, University of Dundee, School of Medicine Ninewells Hospital and Medical School, Dundee, Scotland, UK
| | - Jayne Digby
- Centre for Research into Cancer Prevention and Screening, University of Dundee, School of Medicine, Ninewells Hospital and Medical School, Dundee, Scotland, UK
| | - Judith A Strachan
- Department of Blood Sciences, Ninewells Hospital and Medical School, NHS Tayside, Dundee, Scotland, UK
| | - Rebecca K McCann
- Department of Blood Sciences, Ninewells Hospital and Medical School, NHS Tayside, Dundee, Scotland, UK
| | - Francis A Carey
- Department of Pathology, Ninewells Hospital and Medical School, NHS Tayside, Dundee, Scotland, UK
| | - Callum G Fraser
- Centre for Research into Cancer Prevention and Screening, University of Dundee, School of Medicine, Ninewells Hospital and Medical School, Dundee, Scotland, UK
| | - Robert Jc Steele
- Centre for Research into Cancer Prevention and Screening, University of Dundee, School of Medicine, Ninewells Hospital and Medical School, Dundee, Scotland, UK
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O'Reilly SM, MacNally S, O'Donoghue D, Mooney T, Fitzpatrick P, Mulcahy HE, Cullen G. Correlation of Fecal Immunochemical Testing Levels With Pathology Results in a National Colorectal Cancer Screening Program. Clin Transl Gastroenterol 2021; 12:e00277. [PMID: 33512944 PMCID: PMC7806233 DOI: 10.14309/ctg.0000000000000277] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 06/08/2020] [Indexed: 12/31/2022] Open
Abstract
INTRODUCTION Fecal immunochemical testing (FIT) positivity is determined by a threshold decided by individual screening programs. Data are limited on correlation between FIT levels and pathology identified at colonoscopy. Our aim was to examine the correlation between FIT levels and pathology identified in a national colorectal cancer screening program. METHODS FIT levels (n = 9,271) were analyzed and correlated with patient demographics and pathology identified, including adenomas, sessile serrated lesions, number/size of adenomas, and presence of dysplasia. Levels were divided into 2 categories: FIT levels were defined as "high" or "low" based on whether they were above or below the median (479 ngHb/mL). Multivariate analysis was performed. RESULTS A total of 8,084 patients (87%) underwent colonoscopy. Those younger than 65 years (odds ratio [OR] 1.267, 95% confidence interval [CI] 1.107-1.45, P = 0.001), those with an adenoma >10 mm (OR 1.736, 95% CI 01.512-1.991, P < 0.001), and those with left-sided adenomas (OR 1.484, 95% CI 1.266-1.74, P < 0.001) had higher FIT levels. Cancers (OR 2.8, 95% CI 2.09-3.75, P < 0.001) and high-grade dysplasia (OR 1.356, 95% CI 1.08-1.7, P = 0.008) had higher FIT levels, but varied greatly. The number of adenomas was not significant. DISCUSSION In this study, FIT levels were high for left-sided and large adenomas, suggesting that FIT has poor sensitivity for detection of diminutive and right-sided neoplasia. FIT levels had no association with gender and declined with age. Adenoma burden did not correlate with FIT levels; this is a novel finding. FIT levels vary greatly even in those with advanced neoplasia; therefore, FIT is unlikely to be useful as a risk stratification tool.
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Affiliation(s)
- Susanne M. O'Reilly
- Center for Colorectal Disease, St Vincent's University Hospital, Dublin 4, Ireland
| | - Sara MacNally
- National Screening Service, Kings Inn House, Dublin 1, Ireland
| | | | - Therese Mooney
- National Screening Service, Kings Inn House, Dublin 1, Ireland
| | | | - Hugh E. Mulcahy
- Center for Colorectal Disease, St Vincent's University Hospital, Dublin 4, Ireland
| | - Garret Cullen
- Center for Colorectal Disease, St Vincent's University Hospital, Dublin 4, Ireland
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Högberg C, Gunnarsson U, Jansson S, Thulesius H, Cronberg O, Lilja M. Diagnosing colorectal cancer in primary care: cohort study in Sweden of qualitative faecal immunochemical tests, haemoglobin levels, and platelet counts. Br J Gen Pract 2020; 70:e843-e851. [PMID: 33139332 PMCID: PMC7643823 DOI: 10.3399/bjgp20x713465] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 05/13/2020] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) diagnostics are challenging in primary care and reliable diagnostic aids are desired. Qualitative faecal immunochemical tests (FITs) have been used for suspected CRC in Sweden since the mid-2000s, but evidence regarding their effectiveness is scarce. Anaemia and thrombocytosis are both associated with CRC. AIM To evaluate the usefulness of qualitative FITs requested for symptomatic patients in primary care, alone and combined with findings of anaemia and thrombocytosis, in the diagnosis of CRC. DESIGN AND SETTING A population-based cohort study using electronic health records and data from the Swedish Cancer Register, covering five Swedish regions. METHOD Patients aged ≥18 years in the five regions who had provided FITs requested by primary care practitioners from 1 January 2015 to 31 December 2015 were identified. FIT and blood-count data were registered and all CRC diagnoses made within 2 years were retrieved. Diagnostic measurements were calculated. RESULTS In total, 15 789 patients provided FITs (four different brands); of these patients, 304 were later diagnosed with CRC. Haemoglobin levels were available for 13 863 patients, and platelet counts for 10 973 patients. Calculated for the different FIT brands only, the sensitivities for CRC were 81.6%-100%; specificities 65.7%-79.5%; positive predictive values 4.7%-8.1%; and negative predictive values 99.5%-100%. Calculated for the finding of either a positive FIT or anaemia, the sensitivities increased to 88.9-100%. Adding thrombocytosis did not further increase the diagnostic performance. CONCLUSION Qualitative FITs requested in primary care seem to be useful as rule-in tests for referral when CRC is suspected. A negative FIT and no anaemia indicate a low risk of CRC.
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Affiliation(s)
| | - Ulf Gunnarsson
- Department of Surgical and Perioperative Sciences, Umeå University, Umeå
| | - Stefan Jansson
- University Health Care Research Centre, Örebro University, Örebro
| | - Hans Thulesius
- Department of Clinical Sciences, Lund University, Malmö; professor of primary care, Department of Medicine and Optometry, Linnaeus University, Kalmar
| | - Olof Cronberg
- Department of Clinical Sciences, Lund University, Malmö
| | - Mikael Lilja
- Department of Public Health and Clinical Medicine
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Hull MA, Rees CJ, Sharp L, Koo S. A risk-stratified approach to colorectal cancer prevention and diagnosis. Nat Rev Gastroenterol Hepatol 2020; 17:773-780. [PMID: 33067592 PMCID: PMC7562765 DOI: 10.1038/s41575-020-00368-3] [Citation(s) in RCA: 86] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/08/2020] [Indexed: 02/06/2023]
Abstract
Population screening and endoscopic surveillance are used widely to prevent the development of and death from colorectal cancer (CRC). However, CRC remains a major cause of cancer mortality and the increasing burden of endoscopic investigations threatens to overwhelm some health services. This Perspective describes the rationale for and approach to improved risk stratification and decision-making for CRC prevention and diagnosis. Limitations of current approaches will be discussed using the UK as an example of the challenges faced by a particular health-care system, followed by discussion of novel risk biomarker utilization. We explore how risk stratification will be advantageous to current health-care providers and users, enabling more efficient use of limited colonoscopy resources. We discuss risk stratification in the setting of population screening as well as the surveillance of high-risk groups and investigation of symptomatic patients. We also address challenges in the development and validation of risk stratification tools and identify key research priorities.
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Affiliation(s)
- Mark A Hull
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
| | - Colin J Rees
- Population Health Sciences Institute, Newcastle University, Newcastle, UK
| | - Linda Sharp
- Population Health Sciences Institute, Newcastle University, Newcastle, UK
| | - Sara Koo
- Population Health Sciences Institute, Newcastle University, Newcastle, UK
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40
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Khan AA, Klimovskij M, Harshen R. Accuracy of faecal immunochemical testing in patients with symptomatic colorectal cancer. BJS Open 2020; 4:1180-1188. [PMID: 32949085 PMCID: PMC7709370 DOI: 10.1002/bjs5.50346] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Accepted: 07/23/2020] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND The aim of this study was to determine the diagnostic accuracy of the faecal immunochemical test (FIT) for detecting colorectal cancer in symptomatic patients. METHODS This was a prospective study of patients with bowel symptoms. Stool samples were collected during rectal examination. The HM-JACKarc assay (Kyowa Medex, Tokyo, Japan) was used to quantify faecal haemoglobin (Hb); positive results were those with at least 10 μg Hb/g faeces. Two-by-two tables and receiver operating characteristic (ROC) curve analysis were used to determine diagnostic accuracy; χ2 and Mann-Whitney U tests were used to compare other parameters. RESULTS A total of 928 patients were included (M : F ratio 1 : 1·5; median age 72 (i.q.r. 64-80) years). The overall prevalence of colorectal cancer was 5·1 per cent. The FIT had sensitivity of 85·1 per cent, specificity of 83·5 per cent, positive predictive value of 22·6 per cent and negative predictive value of 99·0 per cent. ROC analysis of FIT for diagnosing colorectal cancer gave an area under the curve value of 0·89 (95 per cent c.i. 0·84 to 0·94). Significant bowel pathology was detected more frequently in FIT-positive patients (35·1 per cent versus 7·1 per cent in FIT-negative patients; P < 0·001). There were sex differences in FIT positivity (23·7 per cent in men versus 17·4 per cent in women; P = 0·019); the sensitivity of FIT for colorectal cancer in women was also low. False-negative FIT results were found mainly in women referred with iron-deficiency anaemia, who were found to have caecal cancer. CONCLUSION FIT effectively excluded colorectal cancer in symptomatic patients. Integration of FIT into the diagnostic pathway for colorectal cancer would direct resources appropriately to patients with a greater likelihood of having the disease.
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Affiliation(s)
- A. A. Khan
- Departments of SurgeryConquest Hospital, St Leonards‐on‐Sea, and Eastbourne District General HospitalEastbourneUK
| | - M. Klimovskij
- Departments of SurgeryConquest Hospital, St Leonards‐on‐Sea, and Eastbourne District General HospitalEastbourneUK
| | - R. Harshen
- Departments of SurgeryConquest Hospital, St Leonards‐on‐Sea, and Eastbourne District General HospitalEastbourneUK
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Navarro M, Hijos G, Sostres C, Lué A, Puente-Lanzarote JJ, Carrera-Lasfuentes P, Lanas A. Reducing the Cut-Off Value of the Fecal Immunochemical Test for Symptomatic Patients Does Not Improve Diagnostic Performance. Front Med (Lausanne) 2020; 7:410. [PMID: 32984360 PMCID: PMC7492376 DOI: 10.3389/fmed.2020.00410] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 06/29/2020] [Indexed: 12/17/2022] Open
Abstract
Introduction: The fecal immunochemical test (FIT) has been established as a cost-effective test in colon cancer screening programmes. This test could also be helpful in symptomatic patients prior to colonoscopy, but data about diagnostic performance, and accurate cut-off values for these patients are still scarce. Materials and Methods: Prospective study that included consecutive unselected patients with gastrointestinal symptoms referred for colonoscopy between November 2016 and June 2018. We performed a FIT (FOB Gold® test, cut-off 20 micrograms of Hb/gram of feces) prior to colonoscopy and determined the accuracy of FIT in terms of sensitivity, specificity, positive and negative predictive value for clinically significant pathology, advanced neoplasia, and colorectal cancer in symptomatic patients, using two different cut-off values. Results: A total of 727 patients (44.3% men, aged 58.5 ± 14.9 years) was included in the study. The main symptom was history of previous (non-active) rectal bleeding (34.7%), followed by diarrhea (15.0%). Over one quarter of the patients (25.9%) had a positive FIT result. The caecal intubation rate was 95.5%. Clinically significant pathology was identified in 142 colonoscopies (19.5%), advanced neoplasia in 115 (15.8%) and colorectal cancer in 36 colonoscopies (5.0%). FIT performed very well for clinically significant pathology, advanced neoplasia and cancer, with a high negative predictive value (NPV). Reducing the cut-off value to 10 μg/g yielded similar NPV results, with a decrease in specificity. Using a combination of symptoms with a positive FIT result did not improve FIT performance. Only specificity was slightly higher compared to FIT alone, but this was paralleled by a decrease in sensitivity and NPV for cancer and clinically significant pathology. The odds of presenting clinically significant pathology, advanced neoplasia, or cancer increased with FIT concentration. Conclusions: The specificity and NPV of FIT for clinically significant pathology, advanced neoplasia, and cancer are high in symptomatic patients. FIT is a helpful test for determining the need to perform further studies. It may not be necessary to reduce the cut-off value for symptomatic patients, since FIT performance with the current standard cut-off value used in colorectal cancer screening was accurate. FIT can be used to avoid or prioritize colonoscopy procedures.
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Affiliation(s)
- Mercedes Navarro
- Digestive Diseases Service, University Clinic Hospital, Zaragoza, Spain
| | - Gonzalo Hijos
- Digestive Diseases Service, University Clinic Hospital, Zaragoza, Spain
| | - Carlos Sostres
- Digestive Diseases Service, University Clinic Hospital, Zaragoza, Spain
| | - Alberto Lué
- Digestive Diseases Service, University Clinic Hospital, Zaragoza, Spain
| | | | | | - Angel Lanas
- Digestive Diseases Service, University Clinic Hospital, Zaragoza, Spain.,CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), Zaragoza, Spain.,Department of Medicine, University of Zaragoza, Zaragoza, Spain.,IIS Aragón, Zaragoza, Spain
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Nicholson BD, James T, Paddon M, Justice S, Oke JL, East JE, Shine B. Faecal immunochemical testing for adults with symptoms of colorectal cancer attending English primary care: a retrospective cohort study of 14 487 consecutive test requests. Aliment Pharmacol Ther 2020; 52:1031-1041. [PMID: 32677733 DOI: 10.1111/apt.15969] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 06/02/2020] [Accepted: 06/25/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Faecal immunochemical testing (FIT) is recommended by the National Institute for Health and Care Excellence (NICE) to triage symptomatic primary care patients for further investigation of colorectal cancer. AIM To ascertain the diagnostic performance of FIT in symptomatic adult primary care patients. METHODS Faecal samples from routine primary care practice in Oxfordshire, UK were analysed using the HM-JACKarc FIT method between March 2017 and March 2020. Clinical details were recorded. Patients were followed for up to 36 months in linked hospital records for evidence of benign and serious (colorectal cancer, high-risk adenomas and bowel inflammation) colorectal disease. The diagnostic accuracy of FIT is reported by gender, age group and FIT threshold. RESULTS In 9896 adult patients with at least 6-month follow-up, a FIT result ≥10 µg Hb/g faeces had a sensitivity for colorectal cancer of 90.5% (95% CI 84.9%-96.1%), specificity 91.3% (90.8%-91.9%), positive predictive value (PPV) 10.1% (8.15%-12.0%) and negative predictive value (NPV) 99.9% (99.8%-100.0%). The PPV and specificity for serious colorectal disease were higher and the sensitivity and NPV lower than for colorectal cancer alone. The area under the curve for all adults did not change substantially by gender or by increasing the minimum age of testing. Using ≥10 µg Hb/g faeces, 10% of adults would be investigated to detect 91% of cancers, a number needed to scope of ten to detect one cancer. Using ≥7, ≥50 and ≥150 µg Hb/g faeces, 11%, 4% and 3% of adults would be investigated, and 91%, 74% and 54% cancers detected, respectively. CONCLUSION A FIT threshold of ≥10 µg Hb/g faeces would be appropriate to triage adult patients presenting to primary care with symptoms of serious colorectal disease. FIT may be used to reprioritise patients referred with colorectal cancer symptoms whose investigations have been delayed by the COVID-19 pandemic.
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Affiliation(s)
- Brian D Nicholson
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Tim James
- Department of Clinical Biochemistry, John Radcliffe Hospital, Oxford University Hospitals Trust, Oxford, UK
| | - Maria Paddon
- Department of Clinical Biochemistry, John Radcliffe Hospital, Oxford University Hospitals Trust, Oxford, UK
| | - Steve Justice
- Department of Clinical Biochemistry, John Radcliffe Hospital, Oxford University Hospitals Trust, Oxford, UK
| | - Jason L Oke
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - James E East
- Translational Gastroenterology Unit, and Oxford NIHR Biomedical Research Centre, John Radcliffe Hospital, University of Oxford, Oxford, UK.,Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Brian Shine
- Department of Clinical Biochemistry, John Radcliffe Hospital, Oxford University Hospitals Trust, Oxford, UK
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McFarlanE M, MozdiaK E, Daulton E, Arasaradnam R, Covington J, Nwokolo C. Pre-analytical and analytical variables that influence urinary volatile organic compound measurements. PLoS One 2020; 15:e0236591. [PMID: 32735600 PMCID: PMC7394370 DOI: 10.1371/journal.pone.0236591] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 07/08/2020] [Indexed: 01/25/2023] Open
Abstract
There has been rapidly accelerating interest in the utilization of volatile organic compounds (VOCs) as non-invasive methods for rapid point-of-care medical diagnostics. There is widespread variation in analytical methods and protocols, with little understanding of the effects of sample storage on VOC profiles. This study aimed to determine the effects on VOC profiles of different storage times, at room temperature, prior to freezing, of sealed urine samples from healthy individuals. Analysis using Field Asymmetric Ion Motility Spectrometry (FAIMS) determined the alterations in VOC and total ion count profiles as a result of increasing room temperature storage times. Results indicated that increasing exposure time to room temperature prior to freezing had a threefold effect. Firstly, increased urinary VOC profile variability, with a plateau phase between 12 and 48 hours, before further degradation. Secondly, an increase in total ion count with time exposed to room temperature. Finally, a deterioration in VOCs with each sample run during the analysis process. This provides new insight into the effect of storage of urine samples for VOC analysis using FAIMS technology. Results of this study provide a recommendation for a 12-hour maximum duration at room temperature prior to storage.
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Affiliation(s)
- Michael McFarlanE
- Department of Gastroenterology, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom
- * E-mail:
| | - Ella MozdiaK
- Department of Gastroenterology, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom
| | - Emma Daulton
- School of Engineering, University of Warwick, Coventry, United Kingdom
| | - Ramesh Arasaradnam
- Department of Gastroenterology, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom
- Department of Health Sciences, University of Leicester, United Kingdom
- Faculty of Health Science, University of Coventry, United Kingdom
| | - James Covington
- School of Engineering, University of Warwick, Coventry, United Kingdom
| | - Chuka Nwokolo
- Department of Gastroenterology, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom
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44
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Högberg C, Karling P, Rutegård J, Lilja M. Patient-reported and doctor-reported symptoms when faecal immunochemical tests are requested in primary care in the diagnosis of colorectal cancer and inflammatory bowel disease: a prospective study. BMC FAMILY PRACTICE 2020; 21:129. [PMID: 32611307 PMCID: PMC7331274 DOI: 10.1186/s12875-020-01194-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 06/15/2020] [Indexed: 01/19/2023]
Abstract
BACKGROUND Rectal bleeding and a change in bowel habits are considered to be alarm symptoms for colorectal cancer and they are also common symptoms for inflammatory bowel disease. However, most patients with these symptoms do not have any of these diseases. Faecal immunochemical tests (FITs) for haemoglobin are used as triage tests in Sweden and other countries but little is known about the symptoms patients have when FITs are requested. OBJECTIVE Firstly, to determine patients' symptoms when FITs are used as triage tests in primary care and whether doctors record the symptoms that patients report, and secondly to evaluate the association between symptoms, FIT results and possible prediction of colorectal cancer or inflammatory bowel disease. METHODS AND MATERIALS This prospective study included 364 consecutive patients for whom primary care doctors requested a FIT. Questionnaires including gastrointestinal symptoms were completed by patients and doctors. RESULTS Concordance between symptoms reported from patients and doctors was low. Rectal bleeding was recorded by 43.5% of patients versus 25.6% of doctors, FITs were negative in 58.3 and 52.7% of these cases respectively. The positive predictive value (PPV) of rectal bleeding recorded by patients for colorectal cancer or inflammatory bowel disease was 9.9% (95% confidence interval [CI] 5.2-14.7); for rectal bleeding combined with a FIT the PPV was 22.6% (95% CI 12.2-33.0) and the negative predictive value (NPV) was 98.9% (95% CI 96.7-100). For patient-recorded change in bowel habits the PPV was 6.1% (95% CI 2.4-9.8); for change in bowel habits combined with a FIT the PPV was 18.2% (95% CI 9.1-30.9) and the NPV 100% (95% CI 90.3-100). CONCLUSIONS Doctors should be aware that, during consultations, they do not record all symptoms experienced by patients. FITs requested in primary care, when found positive, may potentially be of help in prioritising referrals, also when patients present with rectal bleeding or change in bowel habits.
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Affiliation(s)
- Cecilia Högberg
- Department of Public Health and Clinical Medicine, Unit of Research, Education and Development – Östersund, Östersund Hospital, Umeå University, Umeå, Sweden
| | - Pontus Karling
- Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden
| | - Jörgen Rutegård
- Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden
| | - Mikael Lilja
- Department of Public Health and Clinical Medicine, Unit of Research, Education and Development – Östersund, Östersund Hospital, Umeå University, Umeå, Sweden
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Chapman C, Thomas C, Morling J, Tangri A, Oliver S, Simpson JA, Humes DJ, Banerjea A. Early clinical outcomes of a rapid colorectal cancer diagnosis pathway using faecal immunochemical testing in Nottingham. Colorectal Dis 2020; 22:679-688. [PMID: 31876975 DOI: 10.1111/codi.14944] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Accepted: 11/29/2019] [Indexed: 12/29/2022]
Abstract
AIM We introduced primary care access to faecal immunochemical testing (FIT) as a stratification tool for symptomatic patients considered to be at risk of colorectal cancer (CRC) prior to urgent referral. We aimed to evaluate clinical and pathway outcomes during the first 6 months of this novel approach. METHOD FIT was recommended for all patients who consulted their general practitioner with lower gastrointestinal symptoms other than rectal bleeding and rectal mass. We undertook a retrospective audit of the results of FIT, related clinical outcomes and resource utilization on prospectively logged cases between November 2017 and May 2018. RESULTS Of the 1862 FIT kits dispatched by post 91.4% were returned, with a median return time of 7 days (range 2-110 days); however, 1.3% of returned kits could not be analysed. FIT results ≥ 150.0 μg haemoglobin (Hb)/g faeces identified patients with a significantly higher risk of CRC (30.9% vs 1.4%, chi-square 167.1, P < 0.0001). FIT results ≥ 10.0 μg Hb/g faeces identified patients with significantly higher risk of significant noncancer bowel pathology (24.1% vs 4.9%, chi-square 73.6, P < 0.0001) and FIT results < 4.0 μg Hb/g faeces identified a group more likely to have non-CRC pathology (5.1% vs 2.4%, chi-square 3.9, P < 0.05). The CRC detection rate in 531 patients investigated after a FIT result of < 4.0 μg Hb/g faeces was 0.2%. In 899 investigated patients, a FIT result with a threshold of 4.0 μg Hb/g faeces had sensitivity 97.2% (85.5-99.9% CI), specificity 61.4% (58.1-64.7% CI), negative predictive value 99.8% (98.7-100.0% CI) and positive predictive value 9.5% (8.7-10.4% CI). CONCLUSION A symptomatic pathway incorporating FIT is feasible and appears more clinically effective than pathways based on age and symptoms alone.
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Affiliation(s)
- C Chapman
- Eastern Hub, Bowel Cancer Screening Programme, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - C Thomas
- Nottingham Colorectal Service, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - J Morling
- Eastern Hub, Bowel Cancer Screening Programme, Nottingham University Hospitals NHS Trust, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
- Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK
| | - A Tangri
- Riverlyn Medical Centre, Nottingham, UK
| | - S Oliver
- Nottingham City Clinical Commissioning Group, Nottingham, UK
| | - J A Simpson
- Nottingham Colorectal Service, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - D J Humes
- Nottingham Colorectal Service, Nottingham University Hospitals NHS Trust, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
- Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK
| | - A Banerjea
- Eastern Hub, Bowel Cancer Screening Programme, Nottingham University Hospitals NHS Trust, Nottingham, UK
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Lué A, Hijos G, Sostres C, Perales A, Navarro M, Barra MV, Mascialino B, Andalucia C, Puente JJ, Lanas Á, Gomollon F. The combination of quantitative faecal occult blood test and faecal calprotectin is a cost-effective strategy to avoid colonoscopies in symptomatic patients without relevant pathology. Therap Adv Gastroenterol 2020; 13:1756284820920786. [PMID: 32523623 PMCID: PMC7235671 DOI: 10.1177/1756284820920786] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 03/20/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Faecal occult blood test (FOBT) has demonstrated effectiveness in colorectal cancer (CRC) screening. Faecal calprotectin (FC) has proven efficient for evaluating activity in inflammatory bowel disease (IBD), but its value in CRC detection is less established. Most symptomatic patients have benign pathologies, but still undergo colonoscopy in many settings. AIMS To evaluate the diagnostic accuracy and cost-effectiveness of the combination of FOBT plus FC in symptomatic patients. METHODS Patients who completed colonic investigations and returned stool samples, on which FOBT and FC were performed, were recruited prospectively. CRC, advanced adenoma, IBD and angiodysplasia were considered as relevant pathologies. RESULTS A total of 404 patients were included, of whom 87 (21.5%) had relevant pathologies. Sensitivity and specificity were 50.6% and 69.6% for FOBT, 78.2% and 54.4% for FC. Negative predictive value (NPV) was 90.1% for FC and 86.9% for FOBT. NPV for the combination of FOBT and FC was 94.1%, with a sensitivity and specificity of 88.5% and 50.3%. The area under ROC (receiver operator curve) (AUC) was 0.741 for FOBT, 0.736 for FC and 0.816 for the combination. The total cost for visits and procedures was €233,016 (€577/patient). Using a combination of FOBT and FC as pre-endoscopic tool allows colonoscopies to be reduced by 39.4%, reducing total costs by 20.5%. CONCLUSION The combination of FOBT and FC has a better diagnostic accuracy compared with each test alone. Performing both tests before colonoscopy is a less costly and more effective strategy, reducing unnecessary procedures and complications.
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Affiliation(s)
- Alberto Lué
- Hospital Clínico Universitario Lozano Blesa, Servicio de Aparato Digestivo, Zaragoza, Spain,Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain
| | | | - Carlos Sostres
- Hospital Clínico Universitario Lozano Blesa, Servicio de Aparato Digestivo, Zaragoza, Spain,Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain,CIBERehd, Madrid, Spain
| | | | - Mercedes Navarro
- Hospital Clínico Universitario Lozano Blesa, Servicio de Aparato Digestivo, Zaragoza, Spain,Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain
| | - Maria Victoria Barra
- Hospital Clínico Universitario Lozano Blesa, Servicio de Bioquímica, Zaragoza, Spain
| | | | | | - Juan José Puente
- Hospital Clínico Universitario Lozano Blesa, Servicio de Bioquímica, Zaragoza, Spain
| | - Ángel Lanas
- Hospital Clínico Universitario Lozano Blesa, Servicio de Aparato Digestivo, Zaragoza, Spain,Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain,CIBERehd, Madrid, Spain Universidad de Zaragoza, Zaragoza, Spain
| | - Fernando Gomollon
- Hospital Clínico Universitario Lozano Blesa, Servicio de Aparato Digestivo, Zaragoza, Spain,Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain,CIBERehd, Madrid, Spain Universidad de Zaragoza, Zaragoza, Spain
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Public preferences for using quantitative faecal immunochemical test versus colonoscopy as diagnostic test for colorectal cancer: evidence from an online survey. BJGP Open 2020; 4:bjgpopen20X101007. [PMID: 32019773 PMCID: PMC7330201 DOI: 10.3399/bjgpopen20x101007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Accepted: 09/12/2019] [Indexed: 10/31/2022] Open
Abstract
BACKGROUND There has been interest in using the non-invasive, home-based quantitative faecal immunochemical test (FIT) to rule out colorectal cancer (CRC) in high-risk symptomatic patients. AIM To elicit public preferences for FIT versus colonoscopy (CC) and its delivery in primary care. DESIGN & SETTING A cross-sectional online survey in England. METHOD A total of 1057 adults (without CRC symptoms and diagnosis) aged 40-59 years were invited from an English online survey panel. Responders were asked to imagine they had been experiencing CRC symptoms that would qualify them for a diagnostic test. Participants were presented with choices between CC and FIT in ascending order of number of CRCs missed by FIT (from 1-10%). It was measured at what number of missed CRCs responders preferred CC over FIT. RESULTS While 150 participants did not want either of the tests when both missed 1% CRCs, the majority (n = 741, 70.0%) preferred FIT to CC at that level of accuracy. However, this preference reduced to 427 (40.4%) when FIT missed one additional cancer. Women were more likely to tolerate missing CRC when using FIT. Having lower numeracy and perceiving a higher level of risk meant participants were less likely to tolerate a false negative test. Most of those who chose FIT preferred to return it by mail (62.2%), to be informed about normal test results by letter (42.1%), and about abnormal test results face to face (32.5%). CONCLUSION While the majority of participants preferred FIT over CC when both tests had the same sensitivity, tolerance for missed CRCs was low.
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Tsapournas G, Hellström PM, Cao Y, Olsson LI. Diagnostic accuracy of a quantitative faecal immunochemical test vs. symptoms suspected for colorectal cancer in patients referred for colonoscopy. Scand J Gastroenterol 2020; 55:184-192. [PMID: 31906738 DOI: 10.1080/00365521.2019.1708965] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objective: Determine diagnostic accuracy of a quantitative faecal immunochemical haemoglobin test (QuikRead go® FIT, Orion Diagnostica Oy) in symptomatic patients referred for colonoscopy, at various cut-offs and for one or two tests.Methods: Patients referred to four endoscopy units in mid-Sweden between 2013 and 2017 provided information on lower abdominal symptoms and faecal samples from two separate days prior to colonoscopy.Results: In all, 5.4% (13/242) patients had colorectal cancer (CRC). For one FIT at cut-off 10 µg Hb/g faeces, sensitivity for CRC was 92% (95% CI 78-100%) and specificity 77% (95% CI 72-83%); equal to 74%; 95% CI 68-80 (178/242) colonoscopies potentially avoidable and one CRC missed. Based on the maximal outcome of two FITs, sensitivity was 100%, specificity 71% (66-77%) and 68%; 95% CI 62-74 (160/237) colonoscopies potentially avoidable. Among 17% (42/242) patients with one FIT of >200 µg Hb/g faeces, 85% (11/13) had CRC. Positive predictive values of FIT varied 16.9-26.2% depending on cut-off and one or two FITs, whereas NPVs were 99% and above in all scenarios.In 60 patients reporting rectal bleeding, one FIT at cut-off 10 µg Hb/g discriminated well between CRC and other conditions (p = .001). In regression models, FIT was more important than age, sex and all symptoms.Conclusion: One or two FITs in symptomatic patients referred for colonoscopy imply powerful risk stratification abilities for CRC, even among patients reporting rectal bleeding. Larger studies in various settings will clarify how to make the best use of this opportunity. Trial registration: Clinicaltrails.gov NCT02491593.
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Affiliation(s)
| | - Per M Hellström
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Yang Cao
- Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Sweden
| | - Louise I Olsson
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Camtö, Örebro University Hospital, Örebro, Sweden
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Qualitative faecal immunochemical tests (FITs) for diagnosing colorectal cancer in patients with histories of rectal bleeding in primary care: a cohort study. Int J Colorectal Dis 2020; 35:2035-2040. [PMID: 32602056 PMCID: PMC7541370 DOI: 10.1007/s00384-020-03672-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/10/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Rectal bleeding is considered an alarm symptom for colorectal cancer (CRC) but it is common and mostly caused by benign conditions. Qualitative faecal immunochemical tests (FITs) for occult blood have been used as diagnostic aids for many years in Sweden when CRC is suspected. The study aimed to evaluate the usefulness of FITs requested by primary care physicians for patients with and without histories of rectal bleeding, in the diagnosis of CRC. METHODS Results of all FITs requested in primary care for symptomatic patients in the Örebro region during 2015 were retrieved. Data on each patient's history of rectal bleeding was gathered from electronic health records. Patients diagnosed with CRC within 2 years were identified from the Swedish Cancer Register. The analysis focused on three-sample FITs, the customary FIT in Sweden. RESULTS A total of 4232 patients provided three-sample FITs. Information about the presence/absence of rectal bleeding was available for 2027 patients, of which 59 were diagnosed with CRC. For 606 patients with the presence of rectal bleeding, the FIT showed sensitivity 96.2%, specificity 60.2%, positive predictive value 9.8% (95% CI 6.1-13.4) and negative predictive value 99.7% (95% CI 99.2-100) for CRC. For 1421 patients without rectal bleeding, the corresponding figures were 100%, 73.6%, 8.3% (95% CI 5.6-10.9) and 100% (95% CI 99.6-100). CONCLUSION The diagnostic performance of a qualitative three-sample FIT provided by symptomatic patients in primary care was similar for those with and without a history of rectal bleeding. FITs seem useful for prioritising patients also with rectal bleeding for further investigation.
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D'Souza N, Abulafi M. The faecal immunochemical test in low risk patients with suspected bowel cancer. Br J Hosp Med (Lond) 2019; 80:22-26. [PMID: 30592674 DOI: 10.12968/hmed.2019.80.1.22] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The National Institute for Health and Care Excellence produced guidance recommending use of the faecal immunochemical test in patients with low risk symptoms for colorectal cancer. At a cut off of 10 μg haemoglobin per gram of faeces, the National Institute for Health and Care Excellence estimated that the sensitivity of the faecal immunochemical test to detect colorectal cancer ranged from 89% to 100%. The authors evaluated the evidence and noted that the data for the use of the faecal immunochemical test were extrapolated from all comers including high risk patients. Data on low risk patients were scarce and weak. Furthermore, faecal immunochemical test results vary by age, sex, deprivation, ethnicity and symptoms. Large national cohort studies are currently underway investigating the role of the faecal immunochemical test in the English population. Clear clinical pathways and rigorous safety netting are essential and should be part of implementing these guidelines to avoid missed cancers.
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Affiliation(s)
- Nigel D'Souza
- Colorectal Research Fellow, Department of Colorectal Surgery, Croydon University Hospital, Croydon CR7 7YE
| | - Muti Abulafi
- Consultant Colorectal Surgeon, Department of Colorectal Surgery, Croydon University Hospital, Croydon
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