Diagnostic yield of endoscopy in patients with abdominal complaints: incremental value of faecal calprotectin on guidelines of appropriateness.

BACKGROUND: European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE) criteria have been developed to increase diagnostic yield, but their predictive value is limited. We investigated the incremental diagnostic value of faecal calprotectin to EPAGE criteria. METHODS: In a post-hoc analysis of a prospective study, EPAGE criteria were applied to 298 of 575 (51.8%) patients who had undergone esophagogastroduodenoscopy (EGD), colonoscopy or both for abdominal complaints at the Division of Gastroenterology & Hepatology at the University Hospital Basel in Switzerland. Faecal calprotectin was measured in stool samples collected within 24 hours before the investigation using an enzyme-linked immunosorbent assay. Final endoscopic diagnoses were blinded to calprotectin values. RESULTS: Of 149 EGDs and 224 colonoscopies, 17.6% and 14.7% respectively were judged inappropriate by EPAGE criteria. Appropriate or uncertain indications revealed more endoscopic findings in both EGD (46.3% vs. 23.1%, P = 0.049) and colonoscopy (23.6% vs. 6.1%, P = 0.041) than inappropriate indications. Median calprotectin levels were higher (81.5 µg/g, interquartile range 26-175, vs. 10 µg/g, IQR 10-22, P < 0.001) and testing was more often positive (>50 µg/g) in patients with endoscopic findings, both in EGD (58.2% vs. 33.0%, P = 0.005) and in colonoscopy (57.3% vs. 7.4%, P < 0.001). The use of faecal calprotectin in addition to EPAGE criteria improved the risk reclassification of patients by endoscopic findings. The calculated net reclassification index was 37.8% (P = 0.002) for EGD and 110.9% (P <0.001) for colonoscopy, thus improving diagnostic yield to 56.8% and 70.2%, respectively. CONCLUSIONS: The use of faecal calprotectin in addition to EPAGE criteria improved diagnostic yield in patients with abdominal complaints.

Value of fecal calprotectin in the evaluation of patients with abdominal discomfort: an observational study.

BACKGROUND: The evaluation of patients with abdominal discomfort is challenging and patient selection for endoscopy based on symptoms is not reliable. We evaluated the diagnostic value of fecal calprotectin in patients with abdominal discomfort. METHODS: In an observational study, 575 consecutive patients with abdominal discomfort referred for endoscopy to the Department of Gastroenterology & Hepatology at the University Hospital Basel in Switzerland, were enrolled in the study. Calprotectin was measured in stool samples collected within 24 hours before the investigation using an enzyme-linked immunosorbent assay. The presence of a clinically significant finding in the gastrointestinal tract was the primary endpoint of the study. Final diagnoses were adjudicated blinded to calprotectin values. RESULTS: Median calprotectin levels were higher in patients with significant findings (N = 212, median 97 µg/g, IQR 43-185) than in patients without (N = 326, 10 µg/g, IQR 10-23, P < 0.001). The area under the receiver operating characteristics curve (AUC) to identify a significant finding was 0.877 (95% CI, 0.85-0.90). Using 50 µg/g as cut off yielded a sensitivity of 73% and a specificity of 93% with good positive and negative likelihood ratios (10.8 and 0.29, respectively). Fecal calprotectin was useful as a diagnostic parameter both for findings in the upper intestinal tract (AUC 0.730, 0.66-0.79) and for the colon (AUC 0.912, 0.88-0.94) with higher diagnostic precision for the latter (P < 0.001). In patients > 50 years, the diagnostic precision remained unchanged (AUC 0.889 vs. 0.832, P = 0.165). CONCLUSION: In patients with abdominal discomfort, fecal calprotectin is a useful non-invasive marker to identify clinically significant findings of the gastrointestinal tract, irrespective of age.

Monoclonal antibody testing for fecal calprotectin is superior to polyclonal testing of fecal calprotectin and lactoferrin to identify organic intestinal disease in patients with abdominal discomfort.

BACKGROUND AND AIMS: Fecal calprotectin and lactoferrin are sensitive markers of mucosal inflammation. We compared three different assays in their ability to identify patients with organic intestinal disease. METHODS: In a post-hoc analysis of a prospective study, we examined 405 unselected patients with abdominal complaints referred for endoscopy to the University Hospital Basel, Switzerland. Calprotectin (EK-CAL, Bühlmann Laboratories, Switzerland; PhiCal, Calpro AS, Norway) and lactoferrin (IBD-Scan, Techlab, USA) were measured using enzyme-linked immunosorbent assays. The presence of a clinically significant endoscopic finding was the primary endpoint of the study. Final diagnoses were adjudicated blinded to calprotectin values. RESULTS: The prevalence of organic intestinal disease was 35.3%. Receiver operating characteristics analysis calculated an area under the curve (AUC) for EK-CAL of 0.918, which was significantly better than for PhiCal (AUC 0.842, P<0.001) and IBD-Scan (AUC 0.830, P=0.003) to identify patients with organic intestinal disease. Overall test accuracy was 88.1% for EK-CAL, 83.7% for PhiCal, and 81.3% for IBD-Scan. Optimal cut-off value calculated for PhiCal and IBD-Scan were lower than recommended by the manufacturer. CONCLUSIONS: Monoclonal testing of calprotectin is superior to both polyclonal calprotectin testing and fecal lactoferrin in identifying symptomatic patients with organic intestinal disease.

Fragility of the esophageal mucosa: a pathognomonic endoscopic sign of primary eosinophilic esophagitis?

BACKGROUND: Primary eosinophilic esophagitis, a chronic inflammatory disorder of the esophagus, evokes recurrent dysphagia. Endoscopy is often unremarkable, and no consensus exists regarding management of resultant dysphagia. The response of a series of patients with primary eosinophilic esophagitis to dilation is reported together with a description of a possibly pathognomonic sign: fragile esophageal mucosa, for which the term "crêpe-paper" mucosa is introduced. METHODS: Five men underwent endoscopy because of dysphagia confirmed (clinically, endoscopically, and histologically) to be caused by primary eosinophilic esophagitis and were treated by bouginage. OBSERVATIONS: All patients had extremely fragile, inelastic, and delicate mucosa, which tore easily even with minor trauma. After the procedure, patients remained asymptomatic for 3 to 24 months. CONCLUSIONS: Primary eosinophilic esophagitis is characterized by fragile esophageal mucosa that readily tears in response to minor trauma during otherwise uneventful diagnostic endoscopy. This "crêpe-paper" sign may alert endoscopists to the presence of the disease when other mucosal alterations are lacking. Dilation is effective for patients with symptoms with minimal morbidity, despite development of disquieting lesions in response to the procedure.

SPINK1/PSTI mutations are associated with tropical pancreatitis and type II diabetes mellitus in Bangladesh.

BACKGROUND & AIMS: Tropical pancreatitis, including tropical calcific pancreatitis and fibrocalculous pancreatic diabetes, is endemic in parts of Asia and Africa. In a preliminary study, we found serine protease inhibitor, Kazal type 1 (SPINK1) mutations in 6 of 8 patients with fibrocalculous pancreatic diabetes in Bangladesh. A more extensive investigation of patients with pancreatic diseases in Bangladesh, including non-insulin-dependent diabetes mellitus, was undertaken. METHODS: Patients with fibrocalculous pancreatic diabetes (n = 22), tropical calcific pancreatitis (n = 15), and non-insulin-dependent diabetes mellitus (n = 43) and controls (n = 76) from Bangladesh were studied. DNA was extracted, and the SPINK1 gene was sequenced in all patients and 50 controls. Exon 3 was sequenced in an additional 26 controls. RESULTS: SPINK1 N34S mutations appeared in 1 of 76 controls (1.3%), 12 of 22 patients with fibrocalculous pancreatic diabetes (55%; odds ratio, 83; P < 0.00001), 3 of 15 with tropical calcific pancreatitis (20%; odds ratio, 11.2; P = 0.04), and 6 of 43 with non-insulin-dependent diabetes mellitus (14%; odds ratio, 11.9; P = 0.009). P55S was present in 2 of 76 controls (3%) and in 1 of 22 patients with fibrocalculous pancreatic diabetes (5%; P = not significant). A novel Y54H (160T>C) mutation was identified in 1 of 15 tropical calcific pancreatitis patients. CONCLUSIONS: In Bangladesh, the SPINK1 N34S mutation increases the risk of several forms of pancreatic disease, including fibrocalculous pancreatic diabetes, tropical calcific pancreatitis, and non-insulin-dependent diabetes mellitus.