Preserving or Resecting the Normal Appendix in Patients Undergoing Laparoscopy Surgery for Suspected Appendicitis

Completed

• Conditions: Acute Appendicitis; Diagnostic Laparoscopy; Neoplasms; Abdominal Pain (AP); Laparoscopic Appendectomy

• Registration Number: NCT06917612
• Lead Sponsor: Herlev Hospital

Brief Summary

When appendicitis is suspected, patients are typically planned for emergency surgery preferably using a laparoscopic approach. Up to 20% of these patients will have a normal appendix, thus not suffering from appendicitis. Surgeons can either perform a normal diagnostic laparoscopy (leave the appendix in situ) or perform a negative appendectomy (resect the normal appendix). International guidelines recommend negative appendectomy based on weak evidence due to the risk of appendix cancer, but some countries and researchers advocate against negative appendectomy as these patients may experience more harm than if the appendix is left in situ. There are limited national guidelines and the decision is often left to the operating surgeon. Surgeons performing negative appendectomies argue that these prevent microappendicitis and the risk of a subsequent episode of appendicitis. As appendix cancers are rare, and a randomised controlled trial including this subgroup of patients with normal appendices undergoing emergency surgery for suspected appendicitis is unfeasible, an emulated target trial is planned.

This target trial aims to evaluate the effect of a normal diagnostic laparoscopy versus negative appendectomy during laparoscopic surgery for suspected appendicitis regarding cancer in the appendix and other complications such as death, reoperation, and readmission.

Detailed Description

The target trial emmulates an unfeasible randomised controlled trial by using observational data to investigate the two treatment strategies (two groups) normal diagnostic laparoscopy versus negative appendectomy when a normal appendix is seen during surgery for suspected appendicitis. The assignment to the treatment strategies during surgery for suspected appendicitis is treated as randomised within the levels of the following baseline covariates; sex, age, year of index surgery, and hospital through inverse probability weighting. We will analyse data according to treatment assignment at baseline (intention-to-treat). Because the treatment strategies in this target trial are surgical, all participants will adhere to the surgical treatment strategy: neither a normal diagnostic laparoscopy nor a negative appendectomy at index surgery can be reversed. However, both may be followed by a reoperation, e.g., a new normal diagnostic laparoscopy or a laparoscopic appendectomy (for suspected appendicitis or stump appendicitis). However, this will not influence analyses but be recorded as an outcome.

As inverse probability weighting has been applied, no further adjustment in the pre-specified analyses below is needed.

The continuous outcome, delay of cancer diagnosis for the normal diagnostic laparoscopy group, will be descriptively reported as mean (SD) or median (IQR).

For dichotomous outcomes, the following analyses are planned:

* Kaplan-Meier curves for each group

* Incidence proportion (risk) including 95% CI for each group

* Relative risk

* Risk difference

* Number needed to treat

* Number needed to harm

* Test chi-square

Study Timeline

• Study Start: 2005-01-01
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31
• Status Verified: 2025-04
• Study First Submitted: 2025-04-01
• Study First Submitted QC: 2025-04-01
• Last Update Submitted: 2025-04-01
• Study First Posted: 2025-04-08
• Last Update Posted: 2025-04-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20000

Inclusion Criteria

• All ages and sexes
• Undergoing laparoscopic surgery for suspected appendicitis from 2005 to 2021
• Resected appendix without inflammation e.g., without appendicitis

Exclusion Criteria

• Previous resection of the appendix (e.g., previous appendectomy, or resection of the gut including the appendix before January 1, 2005) based on data from surgical codes in the Danish National Patient Register
• Unable to be tracked in the Danish registers, such as a replacement personal identification number, or for those not residing in Denmark based on data from the Civil Registration System
• Diagnostic codes indicating appendix cancer at index surgery (C181), thus, not operated for suspected appendicitis
• Laparoscopic appendectomy converted to open surgery or other surgical procedures conducted contaminated with laparoscopic appendectomy, indicated a need for other surgical interventions because of disease

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Cancer in the appendix	2 years	Histopathologically verified cancer in the appendix (primary or metastasis) in the nationwide register the Danish Pathology Data Bank e.g., SNOMED morphology codes for cancer (M8\*\*\*\* or M9\*\*\*\*) in relation to the topography code of the appendix (T66000)
Appendix cancer	2 years	Histopathologically verified appendix cancer (primary) in the nationwide register the Danish Pathology Data Bank e.g., SNOMED morphology codes for cancer (M8\*\*\*\* or M9\*\*\*\*) in relation to the topography code of the appendix (T66000)

Secondary Outcome Measures

Name	Time	Method
Delay in diagnosis of cancer	2 years	Time from index normal diagnostic laparoscopy to histopathologically verified cancer in the appendix in the nationwide register Danish Pathology Data Bank, e.g., SNOMED morphology codes for cancer (M8\*\*\*\* or M9\*\*\*\*) in relation to the topography code of the appendix (T66000)
Death	2 years	All-cause death registered in the nationwide The Civil Registration System
Any reoperation	1 year	Any reoperations registered in the nationwide Danish National Patient Register
Abdominal reoperation	1 year	Abdominal reoperations registered in the nationwide Danish National Patient Register e.g., with surgical codes KJ\*\*\* (gastrointestinal tract), KK\*\*\* (urological), or KL\*\*\*(gynecological)
Resected appendix	2 years	Histopathological record of an appendix in the nationwide register the Danish Pathology Data Bank e.g., record with topography code of the appendix (T66000) after index surgery, including subdivision of morphology codes into appendicitis, negative appendectomy, appendix cancer, and other
Readmission	1 year	Any readmissions registered in the nationwide Danish National Patient Register, including subdivisions into diagnostic codes relating to different diseases