Scandinavian Journal of Gastroenterology. 2015; 50: 272–277
ORIGINAL ARTICLE
Fecal calprotectin in patients with suspected small bowel disease – a selection tool for small bowel capsule endoscopy?
Scand J Gastroenterol Downloaded from informahealthcare.com by Nyu Medical Center on 04/13/15 For personal use only.
PAUL A. S. OLSEN1, REIDAR FOSSMARK1,2 & GUNNAR QVIGSTAD1,2 1
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway, and 2Department of Gastroenterology and Hepatology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
Abstract Objective. Fecal calprotectin (FC) has been proposed as a selection tool for gastrointestinal examinations, but the use of FC in the diagnosis of small bowel disease in particular is less studied. The aim of this study was to assess if FC could be used to predict findings on small bowel capsule endoscopy (SBCE). Material and methods. We retrospectively collected FC values, SBCE findings and clinical data in 161 patients with suspected small bowel disease referred for SBCE. Findings on SBCE were correlated with FC levels and the diagnostic value of FC was assessed. Results. Of the 161 patients, 37.3% had a positive FC and 29.8% had a finding on SBCE. Overall there was a significant difference in FC values between patients with any finding on SBCE and patients with a normal SBCE, but patients with ulcers/erosions was the only subgroup of patients with FC values significantly higher than patients with a normal SBCE. The proportion of patients with findings on SBCE increased with increasing FC value. A positive FC (‡50 mg/kg) had a sensitivity, specificity, positive predictive value and negative predictive value of 54.2%, 69.9%, 43.3% and 78.2%, respectively, for predicting findings on SBCE. Conclusions. FC alone cannot be used as a selection tool for SBCE in patients with suspected small bowel disease in a specialist setting. However, a high FC value implies a higher probability of finding significant pathology on SBCE, and thus strengthens the indication for performing the examination.
Key Words: calprotectin, capsule endoscopy, small bowel
Introduction Diseases of the small bowel are rare. It is estimated that about 5% of gastrointestinal (GI) bleedings and 1–2% of all primary GI tract malignancies originate in the small bowel. Similarly, in patients with Crohn’s disease, isolated involvement of the small intestine proximal to the distal ileum is rare. Previously, the diagnosis of small intestinal disease was challenging due to the inaccessibility of the small intestine to traditional endoscopy, as well as the lack of sensitive radiological methods. In recent years, improved radiological methods and new diagnostic modalities, including small bowel capsule endoscopy (SBCE) and balloon enteroscopy, have revolutionized small
bowel diagnostics and therapy. SBCE is by many considered as ‘gold standard’ for diagnosis of diseases of the small bowel due to its relatively high sensitivity. It is becoming widely available, is easy to perform and have a low complication rate. The method has however a few drawbacks. The specificity is rather low and the clinical significance of the findings can sometimes be difficult to interpret, as healthy individuals may have findings suggestive of disease [1-4]. Selection of patients for SBCE may also be difficult as most GI symptoms are nonspecific, very prevalent in the general population and in most cases caused by irritable bowel syndrome (IBS). Finally, SBCE is time consuming and rather expensive, so good selection tools are needed.
Correspondence: Gunnar Qvigstad, Department of Gastroenterology and Hepatology, St. Olavs Hospital, Trondheim University Hospital, Postboks 3250 Sluppen, N-7006 Trondheim, Norway. E-mail: [email protected]
(Received 21 September 2014; revised 16 November 2014; accepted 17 December 2014) ISSN 0036-5521 print/ISSN 1502-7708 online 2015 Informa Healthcare DOI: 10.3109/00365521.2014.1003395
Scand J Gastroenterol Downloaded from informahealthcare.com by Nyu Medical Center on 04/13/15 For personal use only.
Calprotectin and small bowel disease. Calprotectin is a 36 kDa heterodimer consisting of two proteins that are members of the S100 calciumbinding protein family [5]. It is mainly derived from neutrophils and, to a lesser extent, from monocytes and macrophages, and is released from activated granulocytes and inflamed epithelia as part of the initial innate immune response [6]. It has antimicrobial effects [7], inhibits different metalloproteinases [8] and induces apoptosis in malignant and nonmalignant cell cultures [9]. Since it has been shown that calprotectin is a marker of leukocyte influx into the bowel lumen and correlates well with the excretion of 111Indium-labeled leukocytes [10], it is looked upon as a reliable indicator of GI inflammation [11]. Several studies have shown the utility of measuring fecal calprotectin (FC), especially in the diagnosis and follow-up of patients suffering from inflammatory bowel disease (IBD) [12], and some publications have also found that FC levels may be affected by diseases and conditions like colorectal cancer [13], nonsteroidal anti-inflammatory drug (NSAID) enteropathy [14], diverticular disease [15] and bacterial diarrhea [16]. There is, however, less knowledge of the use of FC in the diagnosis of small bowel diseases. The aim of this study was to assess if FC could be used to predict findings on SBCE in patients with clinically suspected disease of the small bowel, and thus to assess if FC could be used as a selection tool for SBCE. Material and methods We retrospectively analyzed data from consecutive outpatients with clinically suspected disease of the small intestine referred to the Department of Gastroenterology, St. Olavs Hospital, Trondheim University Hospital, for capsule endoscopy between January 1, 2006 and December 31, 2008. During this time period, FC was measured before SBCE as part of the general diagnostic workup in most outpatients at our department, and the patients collected the fecal samples at home 2 weeks before the SBCE procedure. All patients had performed bidirectional flexible endoscopy and a CT or MR enterography without significant (negative or inconclusive) findings before referral to SBCE. Seventy-five of the patients were referred from local hospitals and had completed conventional diagnostic workup there. Clinical data were collected retrospectively for all patients, this included age, gender, indication for referral to capsule endoscopy and the use of antiplatelet drugs, NSAIDs, selective serotonin reuptake inhibitors (SSRIs) and anticoagulants. The highest C-reactive protein (CRP) and the lowest hemoglobin (HGB) concentrations in the symptomatic period and
273
the time from the debut of symptoms until SBCE were recorded. A positive CRP was defined as CRP ‡5 mg/l and anemia was defined as HGB
ORIGINAL ARTICLE
Fecal calprotectin in patients with suspected small bowel disease – a selection tool for small bowel capsule endoscopy?
Scand J Gastroenterol Downloaded from informahealthcare.com by Nyu Medical Center on 04/13/15 For personal use only.
PAUL A. S. OLSEN1, REIDAR FOSSMARK1,2 & GUNNAR QVIGSTAD1,2 1
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway, and 2Department of Gastroenterology and Hepatology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
Abstract Objective. Fecal calprotectin (FC) has been proposed as a selection tool for gastrointestinal examinations, but the use of FC in the diagnosis of small bowel disease in particular is less studied. The aim of this study was to assess if FC could be used to predict findings on small bowel capsule endoscopy (SBCE). Material and methods. We retrospectively collected FC values, SBCE findings and clinical data in 161 patients with suspected small bowel disease referred for SBCE. Findings on SBCE were correlated with FC levels and the diagnostic value of FC was assessed. Results. Of the 161 patients, 37.3% had a positive FC and 29.8% had a finding on SBCE. Overall there was a significant difference in FC values between patients with any finding on SBCE and patients with a normal SBCE, but patients with ulcers/erosions was the only subgroup of patients with FC values significantly higher than patients with a normal SBCE. The proportion of patients with findings on SBCE increased with increasing FC value. A positive FC (‡50 mg/kg) had a sensitivity, specificity, positive predictive value and negative predictive value of 54.2%, 69.9%, 43.3% and 78.2%, respectively, for predicting findings on SBCE. Conclusions. FC alone cannot be used as a selection tool for SBCE in patients with suspected small bowel disease in a specialist setting. However, a high FC value implies a higher probability of finding significant pathology on SBCE, and thus strengthens the indication for performing the examination.
Key Words: calprotectin, capsule endoscopy, small bowel
Introduction Diseases of the small bowel are rare. It is estimated that about 5% of gastrointestinal (GI) bleedings and 1–2% of all primary GI tract malignancies originate in the small bowel. Similarly, in patients with Crohn’s disease, isolated involvement of the small intestine proximal to the distal ileum is rare. Previously, the diagnosis of small intestinal disease was challenging due to the inaccessibility of the small intestine to traditional endoscopy, as well as the lack of sensitive radiological methods. In recent years, improved radiological methods and new diagnostic modalities, including small bowel capsule endoscopy (SBCE) and balloon enteroscopy, have revolutionized small
bowel diagnostics and therapy. SBCE is by many considered as ‘gold standard’ for diagnosis of diseases of the small bowel due to its relatively high sensitivity. It is becoming widely available, is easy to perform and have a low complication rate. The method has however a few drawbacks. The specificity is rather low and the clinical significance of the findings can sometimes be difficult to interpret, as healthy individuals may have findings suggestive of disease [1-4]. Selection of patients for SBCE may also be difficult as most GI symptoms are nonspecific, very prevalent in the general population and in most cases caused by irritable bowel syndrome (IBS). Finally, SBCE is time consuming and rather expensive, so good selection tools are needed.
Correspondence: Gunnar Qvigstad, Department of Gastroenterology and Hepatology, St. Olavs Hospital, Trondheim University Hospital, Postboks 3250 Sluppen, N-7006 Trondheim, Norway. E-mail: [email protected]
(Received 21 September 2014; revised 16 November 2014; accepted 17 December 2014) ISSN 0036-5521 print/ISSN 1502-7708 online 2015 Informa Healthcare DOI: 10.3109/00365521.2014.1003395
Scand J Gastroenterol Downloaded from informahealthcare.com by Nyu Medical Center on 04/13/15 For personal use only.
Calprotectin and small bowel disease. Calprotectin is a 36 kDa heterodimer consisting of two proteins that are members of the S100 calciumbinding protein family [5]. It is mainly derived from neutrophils and, to a lesser extent, from monocytes and macrophages, and is released from activated granulocytes and inflamed epithelia as part of the initial innate immune response [6]. It has antimicrobial effects [7], inhibits different metalloproteinases [8] and induces apoptosis in malignant and nonmalignant cell cultures [9]. Since it has been shown that calprotectin is a marker of leukocyte influx into the bowel lumen and correlates well with the excretion of 111Indium-labeled leukocytes [10], it is looked upon as a reliable indicator of GI inflammation [11]. Several studies have shown the utility of measuring fecal calprotectin (FC), especially in the diagnosis and follow-up of patients suffering from inflammatory bowel disease (IBD) [12], and some publications have also found that FC levels may be affected by diseases and conditions like colorectal cancer [13], nonsteroidal anti-inflammatory drug (NSAID) enteropathy [14], diverticular disease [15] and bacterial diarrhea [16]. There is, however, less knowledge of the use of FC in the diagnosis of small bowel diseases. The aim of this study was to assess if FC could be used to predict findings on SBCE in patients with clinically suspected disease of the small bowel, and thus to assess if FC could be used as a selection tool for SBCE. Material and methods We retrospectively analyzed data from consecutive outpatients with clinically suspected disease of the small intestine referred to the Department of Gastroenterology, St. Olavs Hospital, Trondheim University Hospital, for capsule endoscopy between January 1, 2006 and December 31, 2008. During this time period, FC was measured before SBCE as part of the general diagnostic workup in most outpatients at our department, and the patients collected the fecal samples at home 2 weeks before the SBCE procedure. All patients had performed bidirectional flexible endoscopy and a CT or MR enterography without significant (negative or inconclusive) findings before referral to SBCE. Seventy-five of the patients were referred from local hospitals and had completed conventional diagnostic workup there. Clinical data were collected retrospectively for all patients, this included age, gender, indication for referral to capsule endoscopy and the use of antiplatelet drugs, NSAIDs, selective serotonin reuptake inhibitors (SSRIs) and anticoagulants. The highest C-reactive protein (CRP) and the lowest hemoglobin (HGB) concentrations in the symptomatic period and
273
the time from the debut of symptoms until SBCE were recorded. A positive CRP was defined as CRP ‡5 mg/l and anemia was defined as HGB
