title: Evaluation of the diagnostic accuracy of plasma markers for early diagnosis in patients suspected for acute appendicitis.
abstract: OBJECTIVE
  The main objective of this study was to evaluate the diagnostic accuracy of two novel biomarkers, calprotectin (CP) and serum amyloid A (SAA), along with the more traditional inflammatory markers C-reactive protein (CRP) and white blood cell count (WBC), in patients suspected of having acute appendicitis (AA). The secondary objective was to compare diagnostic accuracy of these biomarkers with a clinical scoring system and radiologic imaging.
  
  
  METHODS
  A total of 233 patients with suspected AA, presenting to the emergency department (ED) between January 2010 and September 2010, and 52 healthy individuals serving as controls, were included in the study. Blood was drawn and CP and SAA-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). CRP and WBC concentrations were routinely measured and retrospectively abstracted from the electronic health record, together with physical examination findings and radiologic reports. The Alvarado score was calculated as a clinical scoring system for AA. Final diagnosis of AA was based on histopathologic examination. The Mann-Whitney U-test was used for between-group comparisons. Receiver operating characteristic (ROC) curves were used to measure the diagnostic accuracy for the tests and to determine the best cutoff points.
  
  
  RESULTS
  Seventy-seven of 233 patients (33%) had proven AA. Median plasma levels for CP and SAA-1 were significantly higher in patients with AA than in those with another final diagnosis (CP, 320.9 ng/mL vs. 212.9 ng/mL; SAA-1, 30 mg/mL vs. 0.6 mg/mL; p < 0.001). CRP and WBC were significantly higher in patients with AA as well. The Alvarado score was helpful at the extremes (<3 or >7). Ultrasound (US) had a sensitivity of 84% and a specificity of 94%. Computed tomography (CT) had a sensitivity of 100% and a specificity of 91%. The area under the ROC (95% confidence interval [CI]) was 0.67 (95% CI = 0.60 to 0.74) for CP, 0.76 (95% CI = 0.70 to 0.82) for SAA, 0.71 (95% CI = 0.64 to 0.78) for CRP, and 0.79 (95% CI = 0.73 to 0.85) for WBC. No cutoff points had high enough sensitivity and specificity to accurately diagnose AA. However, a high sensitivity of 97% was shown at 7.5 × 10(9) /L for WBC and 0.375 mg/mL for SAA.
  
  
  CONCLUSIONS
  CP, SAA-1, CRP, and WBC were significantly elevated in patients with AA. None had cutoff points that could accurately discriminate between AA and other pathology in patients with suspected AA. A WBC < 7.5 × 10(9) /L, with a low level of clinical suspicion for AA, can identify a subgroup of patients who may be sent home without further evaluation, but who should have available next-day follow-up.
authors.affiliation: Department of Surgery, Orbis Medical Center, Sittard-Geleen; Department of Surgery, Maastricht University Medical Center and Nutrition and Toxicology Research Institute Maastricht, Maastricht, the Netherlands.
authors.forename: Dirk H S M
authors.initials: DH
authors.lastname: Schellekens
authors.forename: Karel W E
authors.initials: KW
authors.lastname: Hulsewé
authors.forename: Bernadette A C
authors.initials: BA
authors.lastname: van Acker
authors.forename: Annemarie A
authors.initials: AA
authors.lastname: van Bijnen
authors.forename: Tom M H
authors.initials: TM
authors.lastname: de Jaegere
authors.forename: Suprapto H
authors.initials: SH
authors.lastname: Sastrowijoto
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
authors.forename: Joep P M
authors.initials: JP
authors.lastname: Derikx
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001062:Appendectomy / Q000379:methods; D001064:Appendicitis / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D042241:Early Diagnosis; D004636:Emergency Service, Hospital; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007958:Leukocyte Count; D039841:Leukocyte L1 Antigen Complex / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012680:Sensitivity and Specificity; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein