Salivary biomarker for acute appendicitis in children: a pilot study.

PURPOSE: Assays of salivary biomarkers for diagnosis are gaining popularity in pediatric diseases due to their non-invasive nature. Our pilot project aims to evaluate the utility of salivary leucine-rich-alpha-2-glycoprotein (LRG) in the diagnosis of pediatric acute appendicitis (AA). METHODS: We prospectively recruited 34 patients, aged between 4 and 16 years, admitted with acute abdominal pain suspicious of appendicitis. The patients' demography, clinical characteristics, laboratory investigations, imaging examination results, operative findings, and discharge diagnoses were recorded. We compared the diagnostic performance of the patients' total white counts, neutrophil percentages, C-reactive protein, and saliva LRG levels. Saliva samples were obtained using the SalivaBio Children's Swab and LRG levels were quantified using a commercially available LRG enzyme-linked immunosorbent assay (ELISA) kit. IRB approval was obtained. RESULTS: Seventeen patients had a confirmed diagnosis of appendicitis on histology. Another 17 were confirmed not to have appendicitis after a minimum of 24 h of hospitalization, with further verification via telephone interview 2 weeks later. The median levels of saliva LRG were elevated in patients with AA as compared to those without (P = 0.008). At a cutoff of LRG 0.33 ng/µg, we obtained a diagnostic specificity of 100% and sensitivity of 35.3%. CONCLUSION: Our proof-of-concept study demonstrated the diagnostic potential of saliva LRG for appendicitis in children. The distinct advantage of saliva LRG assays is that the procedure is simple, pain-free, and requires no specialized skill. Further study with a larger cohort is needed to verify our results.

A novel noninvasive appendicitis score with a urine biomarker.

PURPOSE: The aim of our study was to develop an appendicitis score incorporating a urine biomarker, Leucine rich alpha-2-glycoprotein (LRG), for evaluation of children with abdominal pain. METHODS: From January to August 2017 we prospectively enrolled children aged 4-16 years old admitted for suspected appendicitis. Urine samples for LRG analysis were obtained preoperatively and quantified by enzyme-linked immunosorbent assay (ELISA) after correction for patient hydration status. The diagnosis of appendicitis was based on operative findings and histology. Logistic regression was used to identify prospective predictors. RESULTS: A total of 148 patients were recruited, of which 42(28.4%) were confirmed appendicitis. Our Appendicitis Urinary Biomarker (AuB) model incorporated urine LRG with 3 clinical predictors: 'constant pain', 'right iliac fossa tenderness', 'pain on percussion'. Area under the ROC curve for AuB was 0.82 versus 0.78 for the Pediatric Appendicitis Score (PAS) on the same cohort of patients. A model-calculated risk score of <0.15 is interpreted as low risk of appendicitis. Sensitivity for the AuB at this cutoff was 97.6%, specificity 37.7%, negative predictive value 97.6%, positive predictive value 38.3%, and negative likelihood ratio 0.06. CONCLUSION: The noninvasive AuB score appears promising as a diagnostic tool for excluding appendicitis in children without the need for blood sampling. TYPE OF STUDY: Study of diagnostic test. LEVEL OF EVIDENCE: Level III.

The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile.

BACKGROUND: Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints. METHODS: Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides) was used for validation. RESULTS: By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (p < 0.01). Multimarker clustering showed two distinctive proteomic profiles independent of age and ethnicity. Eighteen of 19 cancer samples clustered together (sensitivity 95%) while 27/36 of non-cancer samples clustered in a second group. Nine non-cancer samples that clustered with cancer samples included 5 pre-malignant lesions (1 adenomatous polyp and 4 intestinal metaplasia). Validation using a second sample set showed the sensitivity and specificity to be 88% and 93%, respectively. Positive predictive value of the combined data was 0.80. Selected peptide sequencing identified pepsinogen C and pepsin A activation peptide as significantly down-regulated and alpha-defensin as significantly up-regulated. CONCLUSION: This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.