The Prevalence of Appendiceal Tumours in Periappendicular Abscess

Study Overview
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Brief Summary
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Complicated and uncomplicated appendicitis follow different epidemiological trends also suggesting different pathophysiology behind these two different forms of appendicitis. In 3-10% of patients complicated acute appendicitis is enclosed by formation of a circumscribed periappendicular abscess. The clinically established practice of antibiotic therapy and drainage, if necessary, has been shown safe and effective, allowing the acute inflammatory process to subside in more than 90% of cases without surgery. The need of subsequent interval appendectomy has been questioned with appendicitis recurrence risk varying between 5-26%. During trial enrollment in our randomized Peri-APPAC trial based on the interim analysis results with 17% appendiceal tumor rate in the study population, the trial was prematurely terminated based on ethical concerns. All the follow-up group patients were re-evaluated and surgery was offered and recommended to all follow-up group patients. After this assessment and additional appendectomies, two more tumors were diagnosed resulting in neoplasm rate of 20% in the whole study group all diagnosed in patients over 40 years and the neoplasm rate in patients over 40 years was 29%. Based on high appendiceal tumor rate in patients over 40 years, the appendiceal neoplasm rate needs to be further evaluated in prospective patient cohorts undergoing interval appendectomy as interval appendectomy is generally well tolerated and obliterates the risk of missing a possible tumor. In a recent systematic review of retrospective cohort studies with 13.244 acute appendicitis patients the overall appendiceal tumor rate was 1% after appendectomy, but in patients presenting with appendiceal inflammatory mass the neoplasm rate varied from 10% to 29%. This nationwide prospective multicenter cohort study is designed to assess the prevalence of appendiceal tumors associated with a periappendicular abscess. All consecutive patients presenting with a periappendicular abscess are recommended to undergo interval appendectomy after initial conservative treatment with antibiotic therapy and drainage, if necessary. All patients older than 35 years will undergo laparoscopic interval appendectomy at 2 to 3 months and this is also recommended for the patients between 18 and 35 years of age. Asymptomatic patients under 35 years not willing to undergo interval appendectomy, will undergo a follow-up MRI at 1 year after the initial non-operative treatment.

Detailed Description
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Complicated and uncomplicated appendicitis follow different epidemiological trends also suggesting different pathophysiology behind these two different forms of appendicitis. In 3-10% of patients complicated acute appendicitis is enclosed by formation of a circumscribed periappendicular abscess. The clinically established practice of antibiotic therapy and drainage, if necessary, has been shown safe and effective, allowing the acute inflammatory process to subside in more than 90% of cases without surgery. The need of subsequent interval appendectomy has been questioned with appendicitis recurrence risk varying between 5-26%. During trial enrollment in our randomized Peri-APPAC trial, the high incidence of appendiceal tumors in the study population alarmed the researchers. Based on the interim analysis results with 17% appendiceal tumor rate in the study population, the trial was prematurely terminated based on ethical concerns. All the follow-up group patients were re-evaluated and surgery was offered and recommended to all follow-up group patients. After this assessment and additional appendectomies, two more tumors were diagnosed resulting in neoplasm rate of 20% in the whole study group all diagnosed in patients over 40 years and the neoplasm rate in patients over 40 years was 29%. Based on high appendiceal tumor rate in patients over 40 years, the appendiceal neoplasm rate needs to be further evaluated in prospective patient cohorts undergoing interval appendectomy as interval appendectomy is generally well tolerated and obliterates the risk of missing a possible tumor. In a recent systematic review of retrospective cohort studies with 13.244 acute appendicitis patients the overall appendiceal tumor rate was 1% after appendectomy, but in patients presenting with appendiceal inflammatory mass the neoplasm rate varied from 10% to 29%. This nationwide prospective multicenter cohort study is designed to assess the prevalence of appendiceal tumors associated with a periappendicular abscess. All of the study hospitals will have a common clinical protocol of recommending interval appendectomy to all patients presenting with a periappendicular abscess after initial conservative treatment with antibiotic therapy and drainage, if necessary. Considering the high rate of appendiceal neoplasms, all patients older than 35 years will undergo laparoscopic interval appendectomy at 2 to 3 months after the successful initial non-operative treatment and this is also recommended for the patients between 18 and 35 years of age. Asymptomatic patients under 35 years not willing to undergo interval appendectomy, will undergo a follow-up MRI at 1 year after the initial non-operative treatment.

Official Title
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The Prevalence of Appendiceal Tumours in Patients Presenting With a Periappendicular Abscess - A Nationwide Prospective Cohort Study

Conditions
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Appendix Abscess, Appendicitis, Appendix Mass, Appendix Cancer, Appendix Nec, Appendix Tumor, Appendix Diseases

Intervention / Treatment
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* Procedure: Interval appendectomy
* Diagnostic Test: Follow-up MRI at 1 year


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: periappendiceal abscess proven by CT, Mri or US Exclusion Criteria: patient declines to participate, complicated appendicitis without periappendiceal abscess

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective clinical cohort study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Interval appendectomy<br>For all patients presenting with a periappendicular abscess, an interval appendectomy is planned at 2 to 3 months after initial conservative treatment, which is considered mandatory for all patients over 35 years of age. If a patient is under 35 and asymptomatic and does not want to undergo surgery, a follow-up MRI at 1 year will be performed. | Procedure: Interval appendectomy<br>* interval appendectomy at 2 to 3 months after the initial non-operative treatment<br>|
| Other: Follow-up MRI<br>For all patients presenting with a periappendicular abscess, an interval appendectomy is planned at 2 to 3 months after initial conservative treatment, which is considered mandatory for all patients over 35 years of age. If a patient is under 35 and asymptomatic and does not want to undergo surgery, a follow-up MRI at 1 year will be performed. | Diagnostic Test: Follow-up MRI at 1 year<br>* follow-up MRI at 1 year for asymptomatic patients under 35 years of age not wanting to undergo surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Prevalence of Appendiceal Tumours in Periappendicular Abscess | The Prevalence of Appendiceal Tumours in Patients Presenting With a Periappendicular Abscess - A Nationwide Prospective Cohort Study | 2-3 months (interval appendectomy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tympanic temperature | All patients | Day 0 (on primary admission) | 
| Imaging (primary diagnosis) finding | All patients | Day 0 (on primary admission) | 
| Duration of symptoms on admission | All patients | Day 0 (on primary admission) | 
| Laboratory value: CRP | CRP | Day 0 (on primary admission) up to 3-5 days (discharge from the hospital) | 
| Laboratory value: leuckocytes | leuk | Day 0 (on primary admission) up to 3-5 days (discharge from the hospital) | 
| Laboratory value: neutrophils | neutr | Day 0 (on primary admission) up to 3-5 days (discharge from the hospital) | 
| Laboratory value: hemoglobin | Hb | Day 0 (on primary admission) up to 3-5 days (discharge from the hospital) | 
| Laboratory value: kreatinine | Krea | Day 0 (on primary admission) up to 3-5 days (discharge from the hospital) | 
| Laboratory value: CEA | CEA | Day 0 (on primary admission) up to 3-5 days (discharge from the hospital) and up to 1 year, if no interval appendectomy | 
| Laboratory value. Cg-A | Cg-A | Day 0 (on primary admission) up to 3-5 days (discharge from the hospital)and up to 1 year, if no interval appendectomy | 
| Primary nonoperative treatment | All patients, treatment details | Day 0 and up to one week | 
| Colonoscopy: endoscopic findings and histology | In both intervention groups | 2 weeks to 2 months prior to planned interval appendectomy | 
| Interval appendectomy specimen histology | Interval appendectomy patients | At 3 months | 
| Complications after interval appendectomy | Clavien-Dindo classification, interval appendectomy group | at the time of surgery | 
| Duration of hospital stay | All patients both at primary treatment, interval appendectomy and follow-up | up to 2 years | 
| Follow-up MRI findings | In case the patient does not under interval appendectomy | at 1 year | 
| follow-up CEA | Follow-up MRI patients | at 1 year | 
| follow-up CgA | Follow-up MRI patients | at 1 year | 
| Surgery after follow-up MRI | Follow-up with MRI patients | up to 10 years |