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NCT Number: NCT06917612

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

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.

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Key information

Conditions

Acute Appendicitis Abdominal Pain Abdominal Pain (AP) Appendicitis Cecal Diseases Diagnostic Laparoscopy Digestive System Diseases Gastroenteritis Gastrointestinal Diseases Infections Intestinal Diseases Intraabdominal Infections Laparoscopic Appendectomy Neoplasms Neurologic Manifestations Pain Pathological Conditions, Signs and Symptoms Signs and Symptoms Signs and Symptoms, Digestive

Sex eligibility

All sexes

Study type

Observational

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Normal diagnostic laparoscopy

Procedure

The appendix is left in situ e.g., not resected and no other surgical resection is needed to treat other diseases

Negative appendectomy

Procedure

The appendix is resected but is without histopathological-confirmed inflammation and no other surgical resection is needed to treat other diseases

Primary outcomes

  1. Cancer in the appendix

    Time frame: 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)

  2. Appendix cancer

    Time frame: 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 outcomes

  1. Delay in diagnosis of cancer

    Time frame: 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)

  2. Death

    Time frame: 2 years

    All-cause death registered in the nationwide The Civil Registration System

  3. Any reoperation

    Time frame: 1 year

    Any reoperations registered in the nationwide Danish National Patient Register

  4. Abdominal reoperation

    Time frame: 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)

  5. Resected appendix

    Time frame: 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

  6. Readmission

    Time frame: 1 year

    Any readmissions registered in the nationwide Danish National Patient Register, including subdivisions into diagnostic codes relating to different diseases

Other outcomes

  1. Subgroup analysis for outcomes at 1 year follow-up

    Time frame: 1 year

    Subgroup analyses of all primary and secondary outcomes at the time-point 1 year after index surgery, including 100% of the included participants in the target trial

  2. Subgroup analysis for outcomes at 2 years follow-up

    Time frame: 2 year

    Subgroup analyses of all primary and secondary outcomes at the time-point 2 years after index surgery, including 75% to <100% of the included participants in the target trial

  3. Subgroup analysis for outcomes at 5 years follow-up

    Time frame: 5 year

    Subgroup analyses of all primary and secondary outcomes at the time-point 5 years after index surgery, including as few as 75% of the included participants in the target trial

  4. Sensitivity analysis on comorbidity

    Time frame: 1 year

    For the secondary outcomes (death (2 years), reoperation, and readmission), confounding due to comorbidity will be explored for patients undergoing index surgery from January 1, 2010, and onwards, thus, allowing for calculating Charlson Comorbidity Index based data in the nationwide Danish National Patient Register from 5 years before to index surgery

  5. Sensitivity analysis on umeasured confounding

    Time frame: 2 years

    For the primary outcomes, unmeasured confounding e.g., due to preoperative imaging or perioperative macroscopic suspicion of cancer, will be addressed by calculating the E value

Sponsors and collaborators

Lead sponsor

Herlev Hospital

Other

Collaborators

  • Danish Institute for Public Health

Registry information

Official study title

Normal Diagnostic Laparoscopy Versus Negative Appendectomy in Patients With a Normal Appendix Undergoing Laparoscopic Surgery for Suspected Appendicitis: a Target Trial

Important dates

Study start
2005
Primary completion
2023
Study completion
2023
First posted
Apr 8, 2025
Registry last updated
Apr 8, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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