Explanations for Negative Laparoscopic Appendectomies and Normal Laparoscopies

NCT03349814 | Completed DMC

• 1 other identifier: HEH-TR-1
• Study Type: observational
• Target: 225
• Locations: 1 country
• Sites: 1

Brief Summary

Trial The aim of the study is to investigate which infectious diseases might mimic the symptoms of acute appendicitis to a degree to cause a diagnostic laparoscopy or laparoscopic appendectomy. The primary outcome is to compare the incidence of Yersinia spp. infection in patients, who undergo surgery due to suspected appendicitis, between those with and without appendicitis detected by polymerase chain reaction on rectal swabs. The secondary outcomes are comparison of the incidence of bacterial pathogens (Campylobacter spp., Salmonella spp., Shigella spp., Aeromonas spp.) and Enterobius vermicularis in the two groups. Rectal swabs, appendix swabs, and blood samples are collected prospectively and research biobanks will be established. Initially, the rectal samples and serology samples will be investigated, and possible biomarkers and results of the appendix swabs will be evaluated at a later time point. Ethics The trial will be conducted according to the Helsinki II Declaration after approval from both the local Health Research Ethics Committee and the Danish Data Protection Agency. An informed written consent will be collected from the participants prior to inclusion in the study. Data will be stored according to the approval from the Danish Data Protection Agency. This study is conducted in patients with suspected appendicitis. These patients are fully awake and conscious at time of inclusion. The patients included in this study will not experience any adverse effects due to their participation.

Conditions

Appendicitis; Yersinia Enterocolitica Infection; Yersinia Pseudotuberculosis Infections; Appendectomy

Keywords

appendicitis; appendectomy; yersinia

Outcome Measures

Primary Outcomes (1)

• Detection of infection with Yersinia spp. (enterocolitica and/or pseudotuberculosis) by microbiological investigation of rectal swab

  Specimens (rectal swab) collected prior to surgery are immediately frozen at -80°C and stored at Herlev Hospital in a research biobank. When the last patient has concluded the trial, a fraction of the collected specimens from each patient is sent to the Department of Clinical Microbiology, Hvidovre Hospital and thereafter investigated with a real time PCR for Yersinia spp. These results are noted in the patient's eCRF, but not in the patient's medical record. Samples with a positive PCR result will be cultured for Yersinia spp. and in case of positive culture results, susceptibility testing will be performed (secondary outcome). Hereafter, the collected human material and the cultured Yersinia enterocolitica will be frozen at -80°C and stored for ten years at Hvidovre Hospital as a biobank for future research.

  We follow every patient from admission through surgery and until pathology report approximately ten days after surgery. The analyses are done after the last patient has concluded the trial. We expect the data collection process to take about a year.

Secondary Outcomes (6)

• Serology of Yersinia enterocolitica

  We follow every patient from admission through surgery and until pathology report approximately ten days after surgery. The analyses are done after the last patient has concluded the trial. We expect the data collection process to take about a year.

• Detection of infection with Yersinia spp. by either serology or PCR for Yersinia spp.

  We follow every patient from admission through surgery and until pathology report approximately ten days after surgery. The analyses are done after the last patient has concluded the trial. We expect the data collection process to take about a year.

• Detection of Campylobacter spp.

  We follow every patient from admission through surgery and until pathology report approximately ten days after surgery. The analyses are done after the last patient has concluded the trial. We expect the data collection process to take about a year.

• Detection of Salmonella spp.

  We follow every patient from admission through surgery and until pathology report approximately ten days after surgery. The analyses are done after the last patient has concluded the trial. We expect the data collection process to take about a year.

• Detection of Shigella spp.

  We follow every patient from admission through surgery and until pathology report approximately ten days after surgery. The analyses are done after the last patient has concluded the trial. We expect the data collection process to take about a year.

Study Arms (2)

Appendicitis group

Patients, who undergo a diagnostic laparoscopy, which because of the operative findings leads to an appendectomy, and the appendix is found to be inflamed in the pathology report. A diagnostic laparoscopy where the appendix seems inflamed, and therefore is removed.

Procedure: Diagnostic laparoscopy with appendectomy

Normal appendix group

Patients, who undergo a diagnostic laparoscopy, that either because of the operative findings (mesenteric lymphadenitis or normal diagnostic laparoscopy) does not lead to appendectomy, or leads to appendectomy, but the appendix is not found to be inflamed in the pathology report. A diagnostic laparoscopy where the appendix is not found to be inflamed, and therefore is not removed. OR A diagnostic laparoscopy where the appendix seems inflamed, and therefore is removed, but is not found to be inflamed in the pathology report.

Procedure: Diagnostic laparoscopy without appendectomy; Procedure: Diagnostic laparoscopy with appendectomy

Interventions

Diagnostic laparoscopy without appendectomy PROCEDURE

A diagnostic laparoscopy where the appendix is not found to be inflamed, and therefore is not removed.

Normal appendix group

Diagnostic laparoscopy with appendectomy PROCEDURE

A diagnostic laparoscopy where the appendix seems inflamed, and therefore is removed

Appendicitis group; Normal appendix group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Any adult with suspection of acute appendicits can be included in the study, unless they have known inflammatory bowel disease or another intra-abdominal pathology that appendicitis.

You may qualify if:

• Suspicion of acute appendicitis and planned for diagnostic laparoscopy
• Written informed consent after written and verbal information

You may not qualify if:

• Cannot understand, read or speak Danish
• Known with inflammatory bowel disease
• Other intra-abdominal pathology than appendicitis requiring other surgical intervention or treatment (diagnosed either perioperatively, at a preoperative CT-scan, or shortly after the surgery in the histopathological examination)
• Not undergoing diagnostic laparoscopy, laparoscopic appendectomy, or open appendectomy

Sponsors & Collaborators

• Herlev Hospital: lead

Study Sites (1)

Herlev Hospital

Herlev, Capital Region of Denmark, 2730, Denmark

Location

Related Publications (5)

• Humes DJ, Simpson J. Acute appendicitis. BMJ. 2006 Sep 9;333(7567):530-4. doi: 10.1136/bmj.38940.664363.AE. No abstract available.

  PMID: 16960208 BACKGROUND

• Frisch M, Pedersen BV, Andersson RE. Appendicitis, mesenteric lymphadenitis, and subsequent risk of ulcerative colitis: cohort studies in Sweden and Denmark. BMJ. 2009 Mar 9;338:b716. doi: 10.1136/bmj.b716.

  PMID: 19273506 BACKGROUND

• Slotboom T, Hamminga JT, Hofker HS, Heineman E, Haveman JW; Apple Study Group Appendicitis and Laparoscopic Evaluation. Intraoperative motive for performing a laparoscopic appendectomy on a postoperative histological proven normal appendix. Scand J Surg. 2014 Dec;103(4):245-8. doi: 10.1177/1457496913519771. Epub 2014 Apr 15.

  PMID: 24737848 BACKGROUND

• Fonnes S, Mollerup S, Paulsen SJ, Petersen AM, Holzknecht BJ, Westh H, Rosenberg J. A prospective cohort study of the rectal microbiome in patients with suspected appendicitis. Clin Res Hepatol Gastroenterol. 2025 Sep-Oct;49(8):102675. doi: 10.1016/j.clinre.2025.102675. Epub 2025 Aug 21.

  PMID: 40848874 DERIVED

• Fonnes S, Mollerup S, Paulsen SJ, Holzknecht BJ, Westh H, Rosenberg J. The microbiome of the appendix differs in patients with and without appendicitis: A prospective cohort study. Surgery. 2024 Jun;175(6):1482-1488. doi: 10.1016/j.surg.2024.02.020. Epub 2024 Apr 1.

  PMID: 38565493 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Serology samples: collected for the current research project, analyzed at Statens Serum Institut (SSI), and thereafter anonymized and transferred to the biobank of SSI. EDTA-blood samples, serum-blood samples and buffycoat: collected only for the biobank for future research. Stored for 10 years at Herlev Hospital, and thereafter destroyed. Rectal swab: collected for the current research project. Appendix swab: collected only for the biobank for future research. Stored at Herlev Hospital in the biobank for future research for 10 years, thereafter destroyed.

MeSH Terms

Conditions

Appendicitis; Yersinia Infections; Yersinia pseudotuberculosis Infections

Interventions

Laparoscopy; Appendectomy

Condition Hierarchy (Ancestors)

Intraabdominal Infections; Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Cecal Diseases; Intestinal Diseases; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Endoscopy; Diagnostic Techniques, Surgical; Diagnostic Techniques and Procedures; Diagnosis; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Digestive System Surgical Procedures

Study Officials

• Siv Fonnes, MD

  Centre for Perioperative Optimization, Department of Surgery, Herlev and Gentofte Hospitals, University of Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD-student

Study Record Dates

• First Submitted: November 1, 2017
• First Posted: November 22, 2017
• Study Start: November 21, 2017
• Primary Completion: May 15, 2019
• Study Completion: May 28, 2019
• Last Updated: May 29, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)