Structured management of patients with suspected acute appendicitis

127 Pages·2015·2.42 MB·English

by  Manne Andersson

Linköping University Medical Dissertations
No 1442

Structured management of patients with
suspected acute appendicitis

Manne Andersson

Division of Surgery and Clinical Oncology
Department of Clinical and Experimental Medicine
Faculty of Health Sciences
Linköping University, Sweden

Linköping 2015
Cover illustration: A farmer from Devon, England, 1942, with the divine power of finding water
using only his hands and a hazel twig.
With permission, © Imperial War Museum (D 9817)

© Manne Andersson, 2015
Printed by LiU-Tryck, Linköping University, Sweden, 2011
ISBN 978-91-7519-137-9
ISSN 0345-0082
To my family
Malin, Einar, Line and Elmer
This study has been carried out with the support of
Futurum - Academy for Health and Care, Jönköping County Council, Sweden and
FORSS - Medical Research Council of Southeast Sweden
CONTENTS

LIST OF PUBLICATIONS
ABSTRACT
ABBREVIATIONS
BACKGROUND ................................................................................................ 1
ANATOMY ..................................................................................................................... 1
HISTOLOGY .................................................................................................................. 2
PHYSIOLOGY ................................................................................................................ 2
APPENDICEAL CARCINOMAS .................................................................................. 3
APPENDICITIS .............................................................................................................. 6
Historical aspects ...................................................................................................... 6
Epidemiology ............................................................................................................ 6
Aetiology .................................................................................................................. 7
Definition of appendicitis ......................................................................................... 8
Natural history .......................................................................................................... 9
TREATMENT OF APPENDICITIS ............................................................................ 12
Morbidity and mortality ......................................................................................... 13
DIAGNOSING APPENDICITIS ................................................................................. 15
Signs and symptoms ............................................................................................... 15
Biochemical inflammatory markers ......................................................................... 16
Diagnostic imaging ................................................................................................. 18
Clinical scores ......................................................................................................... 21
PRESENTATION OF DIAGNOSTIC PROPERTIES ................................................ 23
Measures of diagnostic characteristics ..................................................................... 23
MISSING VALUES ...................................................................................................... 28
BOOTSTRAP ............................................................................................................... 29
AIMS OF THE THESIS ................................................................................... 31
PATIENTS AND METHODS .......................................................................... 33
OVERVIEW .................................................................................................................. 33
STUDY DESIGN .......................................................................................................... 34
PATIENTS AND SETTING ........................................................................................ 34
METHODS .................................................................................................................. 35
Data collection ........................................................................................................ 35
Diagnosis ................................................................................................................ 35
Biochemical analyses ............................................................................................... 36
Construction of the AIR score and the extended score (studies I–II) ....................... 37
Validation of the AIR score (studies I–III) .............................................................. 38
Interventions of the STRAPPSCORE study ........................................................... 39
Outcome measures of the STRAPPSCORE study .................................................. 40
Follow-up ............................................................................................................... 41
Statistical methods .................................................................................................. 41
ETHICS ........................................................................................................................ 43
RESULTS ......................................................................................................... 45
DEMOGRAPHIC OVERVIEW ................................................................................... 45
EXCLUDED PATIENTS ............................................................................................. 45
STUDY I ....................................................................................................................... 47
Construction of the score ........................................................................................ 47
Validation of the score ............................................................................................ 48
STUDY II ...................................................................................................................... 50
Discriminating capacity of new inflammatory markers ........................................... 50
Construction of the extended score ......................................................................... 51
Validation of the extended score ............................................................................. 51
STUDY III ..................................................................................................................... 54
STUDY IV ..................................................................................................................... 60
DISCUSSION .................................................................................................. 63
The framework of test development and evaluation ................................................ 63
METHODOLOGICAL CONSIDERATIONS ............................................................ 64
Study design ........................................................................................................... 64
Data collection ........................................................................................................ 67
Data analysis ........................................................................................................... 68
Interventions of the STRAPPSCORE study ........................................................... 69
Randomisation (study IV) ...................................................................................... 71
PRINCIPAL FINDINGS AND INTERPRETATION ................................................. 73
Internal validation and comparison with the Alvarado score ................................... 73
External validation .................................................................................................. 75
Assessment of new inflammatory markers (study ll) ................................................ 79
Effect on outcome (studies III and IV) .................................................................... 79
PROPOSED ALGORITHM.............................................................................. 83
CONCLUSIONS .............................................................................................. 85
FUTURE PERSPECTIVES ............................................................................... 87
SAMMANFATTNING PÅ SVENSKA ............................................................... 89
Delarbete I .............................................................................................................. 90
Delarbete II ............................................................................................................ 91
Delarbete III och IV (STRAPPSCORE-studien) .................................................... 91
Konklusion ............................................................................................................. 92
ACKNOWLEDGEMENTS ............................................................................... 93
REFERENCES .................................................................................................. 95
APPENDIXES ................................................................................................ 111

LIST OF PUBLICATIONS

This thesis is based on the following papers, which will be referred to by their Roman
numerals as indicated below:

I. Andersson M, Andersson RE.
The Appendicitis inflammatory response score: A tool for the diagnosis of acute
appendicitis that outperforms the Alvarado score
World Journal of Surgery. 2008;32(8):1843-49

II. Andersson M, Rubér M, Ekerfelt C, Hallgren HB, Olaison G, Andersson RE.
Can new inflammatory markers improve the diagnosis of acute appendicitis?
World Journal of Surgery. 2014;38(11):2777-83

III. Andersson M, Kolodziej B, Andersson RE.
Structured management of patients with suspected acute appendicitis using a clinical
score and selective imaging (STRAPPSCORE)
Manuscript

IV. Andersson M, Andersson RE.
Routine versus selective diagnostic imaging in patients with intermediate probability
of acute appendicitis. A randomised controlled multicentre study
Submitted manuscript

All previously published papers were reproduced with permission from the publisher
Copyright © Société International de Chirurgie 2008
Copyright © Société International de Chirurgie 2012
Copyright © Société International de Chirurgie 2014