The Prevalence of Appendiceal Tumours in Periappendicular Abscess (PeriAPPAC-T)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Appendicitis; Appendix Cancer; Appendix Mass; Appendix Abscess; Appendix Nec; Appendix Tumor; Appendix Diseases
• Intervention / Treatment: Procedure: Interval appendectomy; Diagnostic test: Follow-up MRI at 1 year

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Paulina Salminen, prof, MD; Phone Number: +35823130000; Email: paulina.salminen@tyks.fi
• Study Contact Backup: Name: Jenny Alajääski, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• periappendiceal abscess proven by CT, Mri or US

Exclusion Criteria:

• patient declines to participate, complicated appendicitis without periappendiceal abscess

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Interval appendectomy; 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; interval appendectomy at 2 to 3 months after the initial non-operative treatment
Other: Follow-up MRI; 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; follow-up MRI at 1 year for asymptomatic patients under 35 years of age not wanting to undergo surgery

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Collaborators: Oulu University Hospital; Kuopio University Hospital; Seinajoki Central Hospital; Tampere University Hospital; Päijänne Tavastia Central Hospital; Vaasa Central Hospital, Vaasa, Finland; Satakunta Central Hospital; Jyväskylä Central Hospital; North Karelia Central Hospital; South Carelia Central Hospital; Mikkeli Central Hospital; Lapland Central Hospital
• Investigators: Principal Investigator: Paulina Salminen, prof, MD, Turku University Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2020
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2035

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 18, 2020

Study Record Updates

• Last Update Posted (Actual): November 18, 2020
• Last Update Submitted That Met QC Criteria: November 17, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Neoplasms; Neoplasms by Site; Inflammation; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Intestinal Neoplasms; Suppuration; Cecal Diseases; Intraabdominal Infections; Cecal Neoplasms; Abscess; Appendicitis; Appendiceal Neoplasms
• Other Study ID Numbers: PeriAPPAC-T

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD is available from the PI upon request, if needed.
• IPD Sharing Time Frame: At study completion
• IPD Sharing Access Criteria: Please see above.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

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