Identification of the optimal treatment strategy for complex appendicitis in the paediatric population: a protocol for a multicentre prospective cohort study (CAPP study)

Paul van Amstel, Roel Bakx, Johanna H van der Lee, Marijke C van der Weide, Rik van Eekelen, Joep P M Derikx, Ernest L W van Heurn, Ramon R Gorter, CAPP collaborative study group, H A Rippen, J Berkhof, B G P Koot, M van der Kuip, R R van Rijn, H J Bonjer, J Jansen, M A Lijkwan, P Boele van Hensbroek, M Springer, F C van Eijck, M D P Luyer, A Jairam, L M de Widt, M Knaapen, C M G Keyzer-Dekker, R Wijnen, G M P Diepenhorst, K M A Dreuning, M M Poelman, D Verver, P van Duijvendijk, M E van der Sande, J W A Oosterhuis, G W Zijp, E H Pasveer, R P R Groenendijk, J L A van Vugt, W J Vles, C A Selles, V B Nieuwenhuijs, J T Hoffman, J W A Leijtens, E G M Vosbeek, C C van Rossem, M P Gaspersz, M H M Bender, B J Corten, E C J Consten, M F J Seesing, T S Bijlsma, S M L The, L E Janssen, V J Leijdekkers, M V Nijenhuis, S M B I Botden, M Joosten, A L A Bloemendaal, C F J M Blanken-Peeters, W M IJgosse, A Meij-de Vries, M M Bruntink, P M N Y H Go, M Pool, S J Oosterling, T C Derksen, A A W van Geloven, T T Poels, J B F Hulscher, F C den Boer, S F Hardon, F P Garssen, T Wagner, M F Lutke Holzik, M B G M Decaestecker, E G Boerma, D Schweitzer, G D Musters, Paul van Amstel, Roel Bakx, Johanna H van der Lee, Marijke C van der Weide, Rik van Eekelen, Joep P M Derikx, Ernest L W van Heurn, Ramon R Gorter, CAPP collaborative study group, H A Rippen, J Berkhof, B G P Koot, M van der Kuip, R R van Rijn, H J Bonjer, J Jansen, M A Lijkwan, P Boele van Hensbroek, M Springer, F C van Eijck, M D P Luyer, A Jairam, L M de Widt, M Knaapen, C M G Keyzer-Dekker, R Wijnen, G M P Diepenhorst, K M A Dreuning, M M Poelman, D Verver, P van Duijvendijk, M E van der Sande, J W A Oosterhuis, G W Zijp, E H Pasveer, R P R Groenendijk, J L A van Vugt, W J Vles, C A Selles, V B Nieuwenhuijs, J T Hoffman, J W A Leijtens, E G M Vosbeek, C C van Rossem, M P Gaspersz, M H M Bender, B J Corten, E C J Consten, M F J Seesing, T S Bijlsma, S M L The, L E Janssen, V J Leijdekkers, M V Nijenhuis, S M B I Botden, M Joosten, A L A Bloemendaal, C F J M Blanken-Peeters, W M IJgosse, A Meij-de Vries, M M Bruntink, P M N Y H Go, M Pool, S J Oosterling, T C Derksen, A A W van Geloven, T T Poels, J B F Hulscher, F C den Boer, S F Hardon, F P Garssen, T Wagner, M F Lutke Holzik, M B G M Decaestecker, E G Boerma, D Schweitzer, G D Musters

Abstract

Introduction: In daily practice large heterogeneity in the treatment of children with complex appendicitis exists. Complex appendicitis can be divided into two subtypes; complex appendicitis with and without appendiceal mass and/or abscess. As complex appendicitis is associated with high morbidity and costs, identification of the optimal treatment strategy is essential. In this article, we present the study protocol for the CAPP (Complex Appendicitis in the Pediatric Population) study.

Methods and analysis: This nation-wide, multi-centre, comparative, non-randomised prospective cohort study includes all children <18 years old with a preoperative suspicion of complex appendicitis, which is based on imaging confirmed acute appendicitis and predefined criteria regarding the severity of appendicitis. Eligible patients are recruited in more than 30 hospitals. Open appendectomy will be compared with laparoscopic appendectomy for children without appendiceal mass and/or abscess and initial non-operative treatment (ie, intravenous antibiotics with or without percutaneous drainage) to direct appendectomy for children with appendiceal mass and/or abscess. Based on historical data supplied by the participating hospitals and an inclusion period of 2 years and 9 months, a sample size of 1308 patients is aimed. Primary outcome is the proportion of patients experiencing any complication at 3 months follow-up. Reported complications will be assessed by an independent adjudication committee. Secondary outcomes include, but are not limited to, quality of life, and (in)direct costs. To adjust for baseline differences and selection bias, outcomes will be compared after propensity score analysis (inverse probability weighting and stratification).

Ethics and dissemination: The Medical Ethics Review Committee of the Amsterdam UMC, location AMC, declared that the Medical Research involving Human Subjects Act (WMO) did not apply to this study. Therefore, no official approval was required by national law. Study results will be presented in peer-reviewed scientific journals and at (inter)national conferences.

Trial registration numbers: NCT04755179; NL9371.

Keywords: paediatric colorectal surgery; paediatric gastroenterology; paediatric surgery.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flowchart of standardised treatment protocol.
Figure 2
Figure 2
Patient flowchart.
Figure 3
Figure 3
Direct Acyclic Graph subgroup 1. ASA, American Society of Anesthesiologists. BMI, Body Mass Index. SIRS, Systemic Inflammatory Response Syndrome.
Figure 4
Figure 4
Direct Acyclic Graph subgroup 2. BMI, Body Mass Index. SIRS, Systemic Inflammatory Response Syndrome

References

    1. Addiss DG, Shaffer N, Fowler BS, et al. . The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol 1990;132:910–25. 10.1093/oxfordjournals.aje.a115734
    1. Anderson JE, Bickler SW, Chang DC, et al. . Examining a common disease with unknown etiology: trends in epidemiology and surgical management of appendicitis in California, 1995-2009. World J Surg 2012;36:2787–94. 10.1007/s00268-012-1749-z
    1. van Rossem CC, Bolmers MDM, Schreinemacher MHF, et al. . Prospective nationwide outcome audit of surgery for suspected acute appendicitis. Br J Surg 2016;103:144–51. 10.1002/bjs.9964
    1. Andersson RE. The natural history and traditional management of appendicitis revisited: spontaneous resolution and predominance of prehospital perforations imply that a correct diagnosis is more important than an early diagnosis. World J Surg 2007;31:86–92. 10.1007/s00268-006-0056-y
    1. Cobben LP, de Van Otterloo AM, Puylaert JB. Spontaneously resolving appendicitis: frequency and natural history in 60 patients. Radiology 2000;215:349–52. 10.1148/radiology.215.2.r00ma08349
    1. Rubér M, Andersson M, Petersson BF, et al. . Systemic Th17-like cytokine pattern in gangrenous appendicitis but not in phlegmonous appendicitis. Surgery 2010;147:366–72. 10.1016/j.surg.2009.09.039
    1. Di Saverio S, Podda M, De Simone B, et al. . Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines. World J Emerg Surg 2020;15:27. 10.1186/s13017-020-00306-3
    1. Gorter RR, Eker HH, Gorter-Stam MAW, et al. . Diagnosis and management of acute appendicitis. EAES consensus development conference 2015. Surg Endosc 2016;30:4668–90. 10.1007/s00464-016-5245-7
    1. Bolmers MD, van Rossem CC, Gorter RR, et al. . Imaging in pediatric appendicitis is key to a low normal appendix percentage: a national audit on the outcome of appendectomy for appendicitis in children. Pediatr Surg Int 2018;34:543–51. 10.1007/s00383-018-4244-2
    1. Markar SR, Blackburn S, Cobb R, et al. . Laparoscopic versus open appendectomy for complicated and uncomplicated appendicitis in children. J Gastrointest Surg 2012;16:1993–2004. 10.1007/s11605-012-1962-y
    1. Cheng Y, Xiong X, Lu J, et al. . Early versus delayed appendicectomy for appendiceal phlegmon or abscess. Cochrane Database Syst Rev 2017;6:CD011670. 10.1002/14651858.CD011670.pub2
    1. Simillis C, Symeonides P, Shorthouse AJ, et al. . A meta-analysis comparing conservative treatment versus acute appendectomy for complicated appendicitis (abscess or phlegmon). Surgery 2010;147:818–29. 10.1016/j.surg.2009.11.013
    1. Bom WJ, Knaapen M, Gorter RR. Revised guideline for acute appendicitis. Amendments to diagnostics and treatment]. Ned Tijdschr Geneeskd 2020;164
    1. Knaapen M, Hall NJ, van der Lee JH, et al. . Establishing a core outcome set for treatment of uncomplicated appendicitis in children: study protocol for an international Delphi survey. BMJ Open 2019;9:e028861. 10.1136/bmjopen-2018-028861
    1. Gorter RR, van den Boom AL, Heij HA, et al. . A scoring system to predict the severity of appendicitis in children. J Surg Res 2016;200:452–9. 10.1016/j.jss.2015.08.042
    1. Dindo D, Demartines N, Clavien P-A. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205–13. 10.1097/
    1. Berríos-Torres SI, Umscheid CA, Bratzler DW, et al. . Centers for disease control and prevention guideline for the prevention of surgical site infection, 2017. JAMA Surg 2017;152:784–91. 10.1001/jamasurg.2017.0904
    1. Varni JW, Seid M, Rode CA. The PedsQL: measurement model for the pediatric quality of life inventory. Med Care 1999;37:126–39. 10.1097/00005650-199902000-00003
    1. Wille N, Badia X, Bonsel G, et al. . Development of the EQ-5D-Y: a child-friendly version of the EQ-5D. Qual Life Res 2010;19:875–86. 10.1007/s11136-010-9648-y
    1. Thayaparan AJ, Mahdi E. The patient satisfaction questionnaire short form (PSQ-18) as an adaptable, reliable, and validated tool for use in various settings. Med Educ Online 2013;18:21747. 10.3402/meo.v18i0.21747
    1. Bouwmans C, Hakkaart-van Roijen L, Koopmanschap M. Handleiding iMTA medical cost questionnaire (iMCQ. Rotterdam: iMTA, Erasmus Universiteit Rotterdam, 2013.
    1. Bouwmans C, Krol M, Severens H, et al. . The iMTA productivity cost questionnaire: a standardized instrument for measuring and Valuing health-related productivity losses. Value Health 2015;18:753–8. 10.1016/j.jval.2015.05.009
    1. Bhangu A, Søreide K, Di Saverio S, et al. . Acute appendicitis: modern understanding of pathogenesis, diagnosis, and management. The Lancet 2015;386:1278–87. 10.1016/S0140-6736(15)00275-5
    1. Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika 1983;70:41–55. 10.1093/biomet/70.1.41
    1. Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res 2011;46:399–424. 10.1080/00273171.2011.568786
    1. Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med 2015;34:3661–79. 10.1002/sim.6607
    1. Castor EDC. Castor electronic data capture, 2019. Available: [Accessed 28 Aug 2019].
    1. van Amstel P, Sluckin TC, van Amstel T, et al. . Management of appendiceal mass and abscess in children; early appendectomy or initial non-operative treatment? A systematic review and meta-analysis. Surg Endosc 2020;34:5234–49. 10.1007/s00464-020-07822-y
    1. Lintula H, Kokki H, Vanamo K, et al. . Laparoscopy in children with complicated appendicitis. J Pediatr Surg 2002;37:1317–20. 10.1053/jpsu.2002.34998
    1. Oka T, Kurkchubasche AG, Bussey JG, et al. . Open and laparoscopic appendectomy are equally safe and acceptable in children. Surg Endosc 2004;18:242–5. 10.1007/s00464-003-8140-y
    1. Minneci PC, Hade EM, Lawrence AE, et al. . Association of Nonoperative management using antibiotic therapy vs laparoscopic appendectomy with treatment success and disability days in children with uncomplicated appendicitis. JAMA 2020;324:581–93. 10.1001/jama.2020.10888
    1. Blakely ML, Williams R, Dassinger MS, et al. . Early vs interval appendectomy for children with perforated appendicitis. Arch Surg 2011;146:660–5. 10.1001/archsurg.2011.6
    1. St Peter SD, Sharp SW, Holcomb GW, et al. . An evidence-based definition for perforated appendicitis derived from a prospective randomized trial. J Pediatr Surg 2008;43:2242–5. 10.1016/j.jpedsurg.2008.08.051
    1. Rasmussen T, Fonnes S, Rosenberg J. Long-Term complications of appendectomy: a systematic review. Scand J Surg 2018;107:189–96. 10.1177/1457496918772379
    1. Hall NJ, Eaton S, Stanton MP, et al. . Active observation versus interval appendicectomy after successful non-operative treatment of an appendix mass in children (China study): an open-label, randomised controlled trial. Lancet Gastroenterol Hepatol 2017;2:253–60. 10.1016/S2468-1253(16)30243-6
    1. Fouad D, Kauffman JD, Chandler NM. Pathology findings following interval appendectomy: should it stay or go? J Pediatr Surg 2020;55:737–41. 10.1016/j.jpedsurg.2019.05.001
    1. Gorter RR, van Amstel P, van der Lee JH, et al. . Unexpected findings after surgery for suspected appendicitis rarely change treatment in pediatric patients; results from a cohort study. J Pediatr Surg 2017;52:1269–72. 10.1016/j.jpedsurg.2017.02.012
    1. Kim SS, Kays DW, Larson SD, et al. . Appendiceal carcinoids in children--management and outcomes. J Surg Res 2014;192:250–3. 10.1016/j.jss.2014.06.031
    1. Otake S, Suzuki N, Takahashi A, et al. . Histological analysis of appendices removed during interval appendectomy after conservative management of pediatric patients with acute appendicitis with an inflammatory mass or abscess. Surg Today 2014;44:1400–5. 10.1007/s00595-014-0950-0
    1. Ein SH, Langer JC, Daneman A. Nonoperative management of pediatric ruptured appendix with inflammatory mass or abscess: presence of an appendicolith predicts recurrent appendicitis. J Pediatr Surg 2005;40:1612–5. 10.1016/j.jpedsurg.2005.06.001
    1. Mahida JB, Lodwick DL, Nacion KM, et al. . High failure rate of nonoperative management of acute appendicitis with an appendicolith in children. J Pediatr Surg 2016;51:908–11. 10.1016/j.jpedsurg.2016.02.056
    1. Tanaka Y, Uchida H, Kawashima H, et al. . Long-term outcomes of operative versus nonoperative treatment for uncomplicated appendicitis. J Pediatr Surg 2015;50:1893–7. 10.1016/j.jpedsurg.2015.07.008

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever