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      Fecal occult blood and calprotectin testing to prioritize primary care patients for colonoscopy referral: The advantage study

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          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.

          Abstract

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          Most cited references29

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          Assessment of Time-to-Treatment Initiation and Survival in a Cohort of Patients With Common Cancers

          Key Points Question What is the association between delays in treatment initiation for common cancers, as are necessary in resource-limited settings and pandemic conditions, with mortality? Findings In this cohort study including 2 241 706 patients with breast, prostate, non-small cell lung, and colon cancer, generally higher all-cause mortality was associated with increasing time to treatment, although the degree varied by cancer type and stage. Patients with colon and lung cancer had the highest mortality associated with increased time to treatment. Meaning These findings emphasize the importance of timely cancer treatment, and, in contrast to current pandemic-related guidelines, support more prompt definitive treatment for intermediate-risk and high-risk prostate cancer.
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            Evidence of advanced stage colorectal cancer with longer diagnostic intervals: a pooled analysis of seven primary care cohorts comprising 11 720 patients in five countries

            Background: The benefits from expedited diagnosis of symptomatic cancer are uncertain. We aimed to analyse the relationship between stage of colorectal cancer (CRC) and the primary and specialist care components of the diagnostic interval. Methods: We identified seven independent data sets from population-based studies in Scotland, England, Canada, Denmark and Spain during 1997–2010 with a total of 11 720 newly diagnosed CRC patients, who had initially presented with symptoms to a primary care physician. Data were extracted from patient records, registries, audits and questionnaires, respectively. Data sets were required to hold information on dates in the diagnostic interval (defined as the time from the first presentation of symptoms in primary care until the date of diagnosis), symptoms at first presentation in primary care, route of referral, gender, age and histologically confirmed stage. We carried out reanalysis of all individual data sets and, using the same method, analysed a pooled individual patient data set. Results: The association between intervals and stage was similar in the individual and combined data set. There was a statistically significant convex (∩-shaped) association between primary care interval and diagnosis of advanced (i.e., distant or regional) rather than localised CRC (P=0.004), with odds beginning to increase from the first day on and peaking at 90 days. For specialist care, we saw an opposite and statistically significant concave (∪-shaped) association, with a trough at 60 days, between the interval and diagnosis of advanced CRC (P<0.001). Conclusions: This study provides evidence that longer diagnostic intervals are associated with more advanced CRC. Furthermore, the study cannot define a specific ‘safe’ waiting time as the length of the primary care interval appears to have negative impact from day one.
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              Faecal haemoglobin and faecal calprotectin as indicators of bowel disease in patients presenting to primary care with bowel symptoms

              Objective In primary care, assessing which patients with bowel symptoms harbour significant disease (cancer, higher-risk adenoma or IBD) is difficult. We studied the diagnostic accuracies of faecal haemoglobin (FHb) and faecal calprotectin (FC) in a cohort of symptomatic patients. Design From October 2013 to March 2014, general practitioners were prompted to request FHb and FC when referring patients with bowel symptoms to secondary care. Faecal samples were analysed for haemoglobin (EIKEN OC-Sensor io) and calprotectin (BÜHLMANN Calprotectin ELISA). Patients triaged to endoscopy were investigated within 6 weeks. All clinicians and endoscopists were blind to the faecal test results. The diagnostic accuracies of FHb and FC for identification of significant bowel disease were assessed. Results 1043 patients returned samples. FHb was detectable in 57.6% (median 0.4 µg/g, 95% CI 0.4 to 0.8; range 0–200). FC at 50 µg/g or above was present in 60.0%. 755 patients (54.6% women, median age 64 years (range 16–90, IQR 52–73)) returned samples and completed colonic investigations. 103 patients had significant bowel disease; the negative predictive values of FHb for colorectal cancer, higher-risk adenoma and IBD were 100%, 97.8% and 98.4%, respectively. Using cut-offs of detectable FHb and/or 200 µg/g FC detected two further cases of IBD, one higher-risk adenoma and no additional cancers. Conclusions In primary care, undetectable FHb is a good ‘rule-out’ test for significant bowel disease and could guide who requires investigation.
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                Author and article information

                Contributors
                fprunes@clinic.cat
                Journal
                United European Gastroenterol J
                United European Gastroenterol J
                10.1002/(ISSN)2050-6414
                UEG2
                United European Gastroenterology Journal
                John Wiley and Sons Inc. (Hoboken )
                2050-6406
                2050-6414
                23 August 2023
                September 2023
                : 11
                : 7 ( doiID: 10.1002/ueg2.v11.7 )
                : 692-699
                Affiliations
                [ 1 ] University Clinic Hospital Lozano Blesa. University of Zaragoza. IIS Aragón. CIBERHED Zaragoza Spain
                [ 2 ] Department of Gastroenterology Hospital Clínic de Barcelona Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) University of Barcelona Barcelona Spain
                [ 3 ] Department of Gastroenterology Hospital Clínico Universitario Lozano Blesa Zaragoza Spain
                [ 4 ] Department of Gastroenterology Hospital Universitario de Canarias Instituto Universitario de Tecnologías Biomédicas (ITB) & Centro de Investigación Biomédica de Canarias (CIBICAN) Universidad de La Laguna Tenerife Spain
                [ 5 ] Department of Gastroenterology Complexo Hospitalario Universitario de Ourense Ourense Spain
                [ 6 ] Department of Gastroenterology Hospital Espirito Santo de Évora Évora Portugal
                [ 7 ] Department of Gastroenterology Hospital Universitario Fundación Alcorcón Madrid Spain
                [ 8 ] Department of Gastroenterology Hospital General Universitario de Alicante Madrid Spain
                [ 9 ] Department of Gastroenterology Hospital Universitario 12 de Octubre Madrid Spain
                [ 10 ] Department of Gastroenterology Hospital Clínico Universitario San Carlos Madrid Spain
                [ 11 ] Department of Gastroenterology Centro Hospitalar São João Porto Portugal
                Author notes
                [*] [* ] Correspondence

                Francesc Balaguer, Department of Gastroenterology, Hospital Clínic, Villarroel 170, 08036 Barcelona, Catalonia, Spain.

                Email: fprunes@ 123456clinic.cat

                Author information
                https://orcid.org/0000-0002-0206-0539
                https://orcid.org/0000-0003-2743-9593
                https://orcid.org/0000-0003-0639-1906
                Article
                UEG212446
                10.1002/ueg2.12446
                10493338
                37614054
                cf3fcf8f-b773-4357-93f2-ee494f0f975d
                © 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 24 March 2023
                : 26 June 2023
                Page count
                Figures: 2, Tables: 3, Pages: 8, Words: 4716
                Funding
                Funded by: Sysmex
                Award ID: This work was supported by Sysmex.
                Funded by: Instituto de Salud Carlos III , doi 10.13039/501100004587;
                Categories
                Original Article
                Endoscopy
                Custom metadata
                2.0
                September 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.3 mode:remove_FC converted:11.09.2023

                colon cancer,colonoscopy,fecal calprotectin,fecal hemoglobin,fecal occult blood

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