Urinary 5-HIAA for Diagnosis of Acute Appendicitis in Children, Does it Help?

BUILDING UP A DIAGNOSTIC MODEL OF ACUTE APPENDICITIS IN CHILDREN USING URINARY 5-HYDROXY INDOL ACETIC ACID

it is randomized control study. two groups of children (n=191) were divided into two groups A and B. Group A included children subjected to the classical protocol of diagnosis of acute appendicitis. this protocol consisted of pediatric appendicitis score evaluation, pelvi abdominal ultrasound and measurement of serum CRP. Group B, children had the same previous assessment plus measurement of urinary 5-HIAA.

Study Overview

• Status: Completed
• Conditions: Diagnosis of Acute Appendicitis in Children
• Intervention / Treatment: Diagnostic test: measurement of urinary 5-HIAA

Detailed Description

1.1- Study design: Patients were randomly categorized into two groups A and B. Randomization was achieved using closed envelop method.

Group A (n= 95) included patients that were evaluated using our institutional protocol. This protocol consists of assessment of children using PAS, ultrasound of abdomen and pelvis and serum levels of C-reactive protein.

Group B (n= 96) included children that were evaluated by our institutional protocol. In addition, all children gave a mid- stream urine sample for spot urinary 5-HIAA detection. Detailed history was taken. This mainly was to exclude cases with history of foods or drugs that may affect level of serotonin in urine such as mono amino oxidase inhibitors.

All related clinical data and laboratory investigations were recorded. 1.2- Quantitation of urinary 5-HIAA level: From each participant, a random urine sample was obtained to assess the urinary 5-HIAA level using a solid phase competitive enzyme-linked immunosorbent assay (ELISA) technique. The commercial kit was purchased and provided by LDN, DN Labor Diagnosika Nord GmbH & Co. Nordhorn, Germany; Catalog #: BA E-1900. As stated by the manufacturer, the urine samples were methylated to derivatize the 5-HIAA. On the provided microtitre plate, the methylated standards, controls and samples are added. 5-HIAA antiserum was then added and incubated for 1 hour. After equilibration, excess free antigen and antigen-antibody complexes are washed out. The affixed bounded antibodies to the solid phase were detected by an anti-rabbit IgG-peroxidase conjugate using TMB as a substrate. The reaction is measured on a microplate reader (Tecan Spectra II, Switzerland), at 450 nm. Quantification of unknown sample concentration is processed by drawing a standard curve with known standard concentrations. The results of 5-HIAA were divided by urinary creatinine and expressed as mg/g creatinine. The inter-assay and intra-assay coefficient of variation were 10.8% and 8.6% respectively.

1.3- Clinical outcome: Diagnosis of acute appendicitis was confirmed by histopathological examination of resected appendix. According to operative findings and pathological reports, the condition ranged from negative appendix to different types of acute appendicitis (catarrhal, suppurative, perforated or gangrenous).

Children did not full filling the requirements for diagnosis as acute appendicitis were discharged on symptomatic treatment or after referral to pediatric emergency department.

Readmitted cases were recorded. 1.4- Statistical analysis: Statistical analysis was done using IBM SPSS V. 24 (IBM, NY, USA). A descriptive analysis was obtained for patients included in the study. Shapiro-Wilk test was conducted to check for normal distribution of dependent variables, such as urinary 5-HIAA, CRP and histopathological findings. X2 test was used to compare the categorical data. Student T-test was used to compare the normally distributed variable between two groups. Mann-Whitney U test and Kruskal-Wallis test were used for comparing the non-normally distributed variables of two and more than two groups, respectively. Binary logistic regression was performed to determine the independent predictors for acute appendicitis and to combine 5-HIAA and PAS results in both groups. Pearson correlation was used for correlating the urinary 5-HIAA with other acute appendicitis predictors. Receiver operating characteristic (ROC) curve was constructed to assess the diagnostic efficacy of acute appendicitis predictors. The optimal cutoff value for each predictor was assessed via the Youden index. The value of AUC ranged from 0.5 to 1.0. The ability of a diagnostic test to identify patients with appendicitis was considered optimal as AUC value reached closer to 1.0. P-value <0.05 was considered significant

• Study Type: Interventional
• Enrollment (Actual): 191
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Gharbeya
    • Tanta, Gharbeya, Egypt, 31111
      • Tanta University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• all children with suspected acute appendicitis

Exclusion Criteria:

• children received drugs that may affect normal values of urinary 5-HIAA as mono mono oxidase inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: group A; subjected to institutional protocol of diagnosis of acute appendicitis	Diagnostic test: measurement of urinary 5-HIAA; urinary assessment of 5-HIAA
Active Comparator: group B; subjected to institutional protocol of diagnosis of acute appendicitis plus measurement of urinary 5-HIAA	Diagnostic test: measurement of urinary 5-HIAA; urinary assessment of 5-HIAA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
accurate diagnosis of acute appendicitis in children	number of cases that have been diagnosed as having acute appendicitis	1 day
decreasing incidence of negative appendectomy	number of cases that are not appendicitis and not operated	1 day
decreasing number of readmitted cases with diagnosis of acute appendicitis	number of cases that had been readmitted with diagnosis of acute appendicitis in both groups	3 days

Collaborators and Investigators

• Sponsor: Tanta University
• Investigators: Principal Investigator: Mohammad G Mohammad, Tanta University

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2017
• Primary Completion (Actual): July 1, 2020
• Study Completion (Actual): July 2, 2020

Study Registration Dates

• First Submitted: August 22, 2020
• First Submitted That Met QC Criteria: August 25, 2020
• First Posted (Actual): August 26, 2020

Study Record Updates

• Last Update Posted (Actual): August 26, 2020
• Last Update Submitted That Met QC Criteria: August 25, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: appendicitis, children, 5-HIAA, scoring systems
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Disease Attributes; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Cecal Diseases; Intraabdominal Infections; Disease; Acute Disease; Appendicitis
• Other Study ID Numbers: 33944/7/20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No