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Is there an added value of faecal calprotectin and haemoglobin in the diagnostic work-up for primary care patients suspected of significant colorectal disease? A cross-sectional diagnostic study

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ABSTRACT

Background: The majority of primary care patients referred for bowel endoscopy do not have significant colorectal disease (SCD), and are – in hindsight – unnecessarily exposed to a small but realistic risk of severe endoscopy-associated complications. We developed a diagnostic strategy to better exclude SCD in these patients and evaluated the value of adding a faecal calprotectin point-of-care (POC) and/or a POC faecal immunochemical test for haemoglobin (FIT) to routine clinical information.

Methods: We used data from a prospective diagnostic study in SCD-suspected patients from 266 Dutch primary care practices referred for endoscopy to develop a diagnostic model for SCD with routine clinical information, which we extended with faecal calprotectin POC (quantitatively in μg/g faeces) and/or POC FIT results (qualitatively with a 6 μg/g faeces detection limit). We defined SCD as colorectal cancer (CRC), inflammatory bowel disease, diverticulitis, or advanced adenoma (>1 cm).

Results: Of 810 patients, 141 (17.4 %) had SCD. A diagnostic model with routine clinical data discriminated between patients with and without SCD with an area under the receiver operating characteristic curve (AUC) of 0.741 (95 % CI, 0.694–0.789). This AUC increased to 0.763 (95 % CI, 0.718–0.809; P = 0.078) when adding the calprotectin POC test, to 0.831 (95 % CI, 0.791–0.872; P < 0.001) when adding the POC FIT, and to 0.837 (95 % CI, 0.798–0.876; P < 0.001) upon combined extension. At a ≥ 5.0 % SCD probability threshold for endoscopy referral, 30.4 % of the patients tested negative based on this combined POC-tests extended model (95 % CI, 25.7–35.3 %), with 96.4 % negative predictive value (95 % CI, 93.1–98.2 %) and 93.7 % sensitivity (95 % CI, 88.2–96.8 %). Excluding the calprotectin POC test from this model still yielded 30.1 % test negatives (95 % CI, 24.7–35.6 %) and 96.0 % negative predictive value (95 % CI, 92.6–97.9 %), with 93.0 % sensitivity (95 % CI, 87.4–96.4 %).

Conclusions: FIT – and to a much lesser extent calprotectin – POC testing showed incremental value for SCD diagnosis beyond standard clinical information. A diagnostic strategy with routine clinical data and a POC FIT test may safely rule out SCD and prevent unnecessary endoscopy referral in approximately one third of SCD-suspected primary care patients.

Conclusions: Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0694-3.

Electronic supplementary material: The online version of this article (doi:10.1186/s12916-016-0684-5) contains supplementary material, which is available to authorized users.

No MeSH data available.


Receiver operating characteristic curves for diagnosing SCD for the basic diagnostic model, and the POC FIT and the calprotectin POC test extended models. FIT faecal immunochemical test for haemoglobin; POC point-of-care; SCD significant colorectal disease. Areas under the curve (before optimism-correction): basic model 0.741 (95 % CI, 0.694–0.789); calprotectin POC test extended 0.763 (95 % CI, 0.718–0.809); POC FIT extended 0.831 (95 % CI, 0.791–0.872); Both faecal POC tests extended 0.837 (95 % CI, 0.798–0.876). Dashed line is reference line
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Fig2: Receiver operating characteristic curves for diagnosing SCD for the basic diagnostic model, and the POC FIT and the calprotectin POC test extended models. FIT faecal immunochemical test for haemoglobin; POC point-of-care; SCD significant colorectal disease. Areas under the curve (before optimism-correction): basic model 0.741 (95 % CI, 0.694–0.789); calprotectin POC test extended 0.763 (95 % CI, 0.718–0.809); POC FIT extended 0.831 (95 % CI, 0.791–0.872); Both faecal POC tests extended 0.837 (95 % CI, 0.798–0.876). Dashed line is reference line

Mentions: The basic model’s AUC increased from 0.741 (95 % CI, 0.694–0.789) to 0.763 (95 % CI, 0.718–0.809; P = 0.078) and 0.831 (95 % CI, 0.791–0.872; P < 0.001) upon extension with POC calprotectin and FIT, respectively, and to 0.837 (95 % CI, 0.798–0.876; P < 0.001) upon combined extension (Fig. 2 and Table 2). All three POC test extended models showed significant net reclassification improvement compared to the basic model. The FIT-only extended model and the combined POC extended model both yielded the highest NRI (both 0.38; see Additional file 1 for the corresponding reclassification tables). When adding FIT to the calprotectin POC extended model, both the AUC and NRI significantly increased, which was not true for adding calprotectin to the FIT extended model (Table 2). The basic model explained 19.0 % of the variation in SCD, which increased to 23.5, 34.5, and 35.8 % for the calprotectin, the FIT, and the combined POC extended models, respectively. All diagnostic models showed excellent calibration (Additional file 1).Fig. 2


Is there an added value of faecal calprotectin and haemoglobin in the diagnostic work-up for primary care patients suspected of significant colorectal disease? A cross-sectional diagnostic study
Receiver operating characteristic curves for diagnosing SCD for the basic diagnostic model, and the POC FIT and the calprotectin POC test extended models. FIT faecal immunochemical test for haemoglobin; POC point-of-care; SCD significant colorectal disease. Areas under the curve (before optimism-correction): basic model 0.741 (95 % CI, 0.694–0.789); calprotectin POC test extended 0.763 (95 % CI, 0.718–0.809); POC FIT extended 0.831 (95 % CI, 0.791–0.872); Both faecal POC tests extended 0.837 (95 % CI, 0.798–0.876). Dashed line is reference line
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Related In: Results  -  Collection

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Fig2: Receiver operating characteristic curves for diagnosing SCD for the basic diagnostic model, and the POC FIT and the calprotectin POC test extended models. FIT faecal immunochemical test for haemoglobin; POC point-of-care; SCD significant colorectal disease. Areas under the curve (before optimism-correction): basic model 0.741 (95 % CI, 0.694–0.789); calprotectin POC test extended 0.763 (95 % CI, 0.718–0.809); POC FIT extended 0.831 (95 % CI, 0.791–0.872); Both faecal POC tests extended 0.837 (95 % CI, 0.798–0.876). Dashed line is reference line
Mentions: The basic model’s AUC increased from 0.741 (95 % CI, 0.694–0.789) to 0.763 (95 % CI, 0.718–0.809; P = 0.078) and 0.831 (95 % CI, 0.791–0.872; P < 0.001) upon extension with POC calprotectin and FIT, respectively, and to 0.837 (95 % CI, 0.798–0.876; P < 0.001) upon combined extension (Fig. 2 and Table 2). All three POC test extended models showed significant net reclassification improvement compared to the basic model. The FIT-only extended model and the combined POC extended model both yielded the highest NRI (both 0.38; see Additional file 1 for the corresponding reclassification tables). When adding FIT to the calprotectin POC extended model, both the AUC and NRI significantly increased, which was not true for adding calprotectin to the FIT extended model (Table 2). The basic model explained 19.0 % of the variation in SCD, which increased to 23.5, 34.5, and 35.8 % for the calprotectin, the FIT, and the combined POC extended models, respectively. All diagnostic models showed excellent calibration (Additional file 1).Fig. 2

View Article: PubMed Central - PubMed

ABSTRACT

Background: The majority of primary care patients referred for bowel endoscopy do not have significant colorectal disease (SCD), and are &ndash; in hindsight &ndash; unnecessarily exposed to a small but realistic risk of severe endoscopy-associated complications. We developed a diagnostic strategy to better exclude SCD in these patients and evaluated the value of adding a faecal calprotectin point-of-care (POC) and/or a POC faecal immunochemical test for haemoglobin (FIT) to routine clinical information.

Methods: We used data from a prospective diagnostic study in SCD-suspected patients from 266 Dutch primary care practices referred for endoscopy to develop a diagnostic model for SCD with routine clinical information, which we extended with faecal calprotectin POC (quantitatively in &mu;g/g faeces) and/or POC FIT results (qualitatively with a 6&nbsp;&mu;g/g faeces detection limit). We defined SCD as colorectal cancer (CRC), inflammatory bowel disease, diverticulitis, or advanced adenoma (&gt;1&nbsp;cm).

Results: Of 810 patients, 141 (17.4&nbsp;%) had SCD. A diagnostic model with routine clinical data discriminated between patients with and without SCD with an area under the receiver operating characteristic curve (AUC) of 0.741 (95&nbsp;% CI, 0.694&ndash;0.789). This AUC increased to 0.763 (95&nbsp;% CI, 0.718&ndash;0.809; P&thinsp;=&thinsp;0.078) when adding the calprotectin POC test, to 0.831 (95&nbsp;% CI, 0.791&ndash;0.872; P&thinsp;&lt;&thinsp;0.001) when adding the POC FIT, and to 0.837 (95&nbsp;% CI, 0.798&ndash;0.876; P&thinsp;&lt;&thinsp;0.001) upon combined extension. At a&thinsp;&ge;&thinsp;5.0&nbsp;% SCD probability threshold for endoscopy referral, 30.4&nbsp;% of the patients tested negative based on this combined POC-tests extended model (95&nbsp;% CI, 25.7&ndash;35.3&nbsp;%), with 96.4&nbsp;% negative predictive value (95&nbsp;% CI, 93.1&ndash;98.2&nbsp;%) and 93.7&nbsp;% sensitivity (95&nbsp;% CI, 88.2&ndash;96.8&nbsp;%). Excluding the calprotectin POC test from this model still yielded 30.1&nbsp;% test negatives (95&nbsp;% CI, 24.7&ndash;35.6&nbsp;%) and 96.0&nbsp;% negative predictive value (95&nbsp;% CI, 92.6&ndash;97.9&nbsp;%), with 93.0&nbsp;% sensitivity (95&nbsp;% CI, 87.4&ndash;96.4&nbsp;%).

Conclusions: FIT &ndash; and to a much lesser extent calprotectin &ndash; POC testing showed incremental value for SCD diagnosis beyond standard clinical information. A diagnostic strategy with routine clinical data and a POC FIT test may safely rule out SCD and prevent unnecessary endoscopy referral in approximately one third of SCD-suspected primary care patients.

Conclusions: Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0694-3.

Electronic supplementary material: The online version of this article (doi:10.1186/s12916-016-0684-5) contains supplementary material, which is available to authorized users.

No MeSH data available.