Small-bowel capsule endoscopy: A ten-point contemporary review

Table 4 Studies evaluating the clinical application of faecal calprotectin in the setting of small-bowel capsule endoscopy

Ref.	Country	Centre	Study type	Design	Participants	FC	CE	Objective(s)	Outcome(s)
Goldstein et al[41]	United States	Multi-centre	Prospective	Double-blind, triple-dummy, placebo controlled	334 healthy subjects	N/A	M2A®; Given®Imaging, Yokneam, Israel	Evaluate incidence of SB injury and correlation with FC in healthy subjects on celecoxib or ibuprofen + omeprazole	►Mean increase in FC higher in subjects on ibuprofen+omeprazole compared with celecoxib alone (P < 0.001);
									►No correlation between FC and SB mucosal breaks
Hawkey et al[42]	Germany, United Kingdom	Multi-centre	Prospective	Double-blind, double-dummy, placebo controlled	139 healthy subjects	Phical Calprotectin Test Kit NovaTec Immunodiagnostica, GmbH Dietzenbac, Germany	M2A®; Given®Imaging, Yokneam, Israel	Investigate SB injury lumiracoxib reduces vs naproxen + omeprazole	►More SB mucosal breaks on naproxen+omeprazole (77.8% vs 40.4%, P < 0.001);
									►Furthermore, higher FC vs placebo (96.8 vs 14.5 μg/g, P < 0.001);
									►27.7% on lumiracoxib had SB mucosal breaks (vs placebo, P = 0.196; vs naproxen, P < 0.001)
									►No increase in FC (-5.7 μg/g; vs placebo, P = 0.377; vs naproxen, P < 0.001)
Smecuol et al[43]	Argentina, Spain, Canada	Multi-centre	Prospective	Non-blinded study	20 healthy subjects	Calprest® Eurospital SpA, Trieste, Italy	M2A®; Given®Imaging, Yokneam, Israel	Determine SB damage by low-dose ASA (on a short-term basis)	►Short-term administration of low-dose ASA associated with mucosal abnormalities of the SB mucosa;
									►Median baseline FC (6.05 μg/g; range: 1.9-79.2 μg/g) increased significantly after ASA use
Werlin et al[44]	United States, Israel, United Kingdom	Multi-centre	Prospective	N/A	42 pts with CF* (aged 10-36 yr); 29 had pancreatic insufficiency	Calprest® Eurospital SpA, Trieste, Italy	PillCam®SB; Given®Imaging, Yokneam, Israel	Examine the SB of pts with CF without overt evidence of GI disease using CE	►Varying degrees of diffuse areas of inflammatory findings in the SB: oedema, erythema, mucosal breaks and frank ulcerations;
									►No adverse events recorded;
									FC markedly high in pts with pancreatic insufficiency, 258 μg/g (normal < 50)
Koulaouzidis et al[45]	United Kingdom	Single centre	Retrospective	Chart review	70 pts with suspected CD and (-) ve bi-directional endoscopy	CALPRO NovaTec Immunodiagnostica GmbH, Dietzenbac, Germany	(1) PillCam®SB; Given®Imaging, Yokneam, Israel; (2) MiroCam®; IntroMedic Co., Seoul, South Korea	Value of FC as selection tool for further investigation of the SB with SBCE, in a cohort of pts with suspected CD	►FC = 50-100 μg/g: normal SBCE, despite symptoms suggestive of IBD;
									►FC > 100 μg/g: good predictor of positive SBCE;
									►FC > 200 μg/g: associated with higher SBCE DY (65%); confirmed CD in 50%;
									►Measurement of FC prior SBCE: useful tool to select patients for referral. If FC < 100 μg/g: SBCE is not indicated (NPV 1.0)
Jensen et al[46]	Denmark	Single centre	Prospective	Blinded study	83 pts from GI OPD clinics with suspected CD	Calprotectin ELISA, BÜHLMANN Laboratories AG, Basel, Switzerland	PillCam®SB; Given®Imaging, Yokneam, Israel	Determine FC levels in CD restricted to SB compared to colonic CD, in pts on first diagnostic work-up; Assess the Sens and Spec of FC in suspected CD	►In pts with SB or colonic CD FC is equal: median 890 μg/g vs 830 mg/kg, respectively (P = 1.0);
									►FC cut-off = 50 μg/g: 92% and 94% Sens for SB and colonic CD, respectively;
									►Overall, Sens and Spec for FC: 95% and 56%;
									►CD was ruled out with NPV of 92%;
									►In suspected CD, FC is effective marker to r/o CD and select patients for endoscopy
Koulaouzidis et al[47]	United Kingdom	Single centre	Retrospective	Chart review	49 pts; known or suspected CD	CALPRO NovaTec Immunodiagnostica GmbH, Dietzenbac, Germany	PillCam®; Given®Imaging, Yokneam, Israel; MiroCam®; IntroMedic Co., Seoul, South Korea	Assess performance of 2 SBCE inflammation scoring systems (LS and CECDAI) correlating them with FC; Define threshold levels for CECDAI	►LS performs better than CECDAI in describing SB inflammation, especially at FC < 100 μg/g
									►CECDAI levels of 3.8 and 5.8 correspond to LS thresholds of 135 and 790, respectively
Sipponen et al[48]	Finland	Single centre	Prospective	Blinded study	84 pts; known or suspected CD	Calprest® Eurospital SpA, Trieste, Italy	PillCam®; Given®Imaging, Yokneam, Israel; MiroCam®; IntroMedic Co., Seoul, South Korea	Study the role of FC and S100A12 in predicting SB inflammatory lesions	►CE abnormal in 35/84 (42%) pts: 14 CD, 8 NSAID-enteropathy, 8 angioectasias, 4 polyps/tumours, 1 ischemic stricture
									►Median FC/S100A12: 22 μg/g (range: 2-342 μg/g)/0.048 μg/g (range: 0.003-1.215 μg/g)
									►FC significantly higher in CD pts (median 91, range: 2-312) compared with pts with normal CE or other abnormalities (P = 0.008)
									►Faecal S100A12 (0.087 μg/g, range: 0.008-0.896 μg/g): no difference between the groups (P = 0.166)
									►Sens, Spec, PPV, NPV in detecting SB inflammation; FC (cut-off 50 μg/g): 59%, 71%, 42%, 83%; S100A12 (cut-off 0.06 μg/g): 59%, 66%, 38%, 82%, respectively

CF: Cystic Fibrosis; CD: Crohn’s disease; GI: Gastrointestinal; OPD: Out-Patient Department; SB: Small-bowel; FC: Faecal calprotectin; ASA: Acetyl-salycylic acid; CE: Capsule endoscopy/e; Pts: Patients; Sens: Sensitivity; Spec: Specificity; SBCE: Small-bowel capsule endoscopy; LS: Lewis score; CECDAI: Capsule endoscopy Crohn’s disease activity index; NPV: Negative predictive value; PPV: Positive predictive value; N/A: Not available or not applicable; NSAID: Non-steroidal anti-inflammatory drug.