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  • Optimal treatment of

    acute cholecystitis

    Charlotte Susan Loozen

  • OPTIMAL TREATMENT OF ACUTE CHOLECYSTITIS

    Thesis, Utrecht University, The Netherlands

    Copyright © by C. S. Loozen, 2017

    Printed by Ipskamp printing

    ISBN 978-94-028-0704-2

    The studies described in Chapter 2, Chapter 3 and Chapter 9 were financially

    supported by the St. Antonius Research Foundation (St. Antonius Onderzoeksfonds)

    Publication of this thesis was financially supported by maatschap heelkunde van het St.

    Antonius Ziekenhuis, raad van bestuur van het St. Antonius Ziekenhuis, Nederlandse

    Vereniging voor Endoscopische Chirurgie and Chipsoft B.V.

  • Optimal treatment of

    acute cholecystitis

    Optimale behandeling van cholecystitis acuta

    (met een samenvatting in het Nederlands)

    PROEFSCHIFT

    Ter verkrijging van de graad van doctor

    aan de Universiteit Utrecht

    op gezag van de rector magnificus, prof. Dr. M.R. Vriens,

    ingevolge het besluit van het college voor promoties

    in het openbaar te verdedigen

    op dinsdag 5 september 2017

    des middags te 4.15

    door

    Charlotte Susan Loozen

    Geboren op 3 februari 1988

    te Haarlem

  • PROMOTOR:

    Prof. dr. M.R. Vriens

    CO-PROMOTOREN:

    Dr. D. Boerma

    Dr. H. C. van Santvoort

  • Aan mijn lieve moedertje

    (en ‘n beetje aan papa)

  • 6 OPTIMAL TREATMENT OF ACUTE CHOLECYSTITIS

    CONTENTS

    CHAPTER 1 General introduction and thesis outline

    9

    PART I TREATMENT STRATEGIES FOR ACUTE CHOLECYSTITIS

    CHAPTER 2 Randomized clinical trial of extended versus single-dose

    perioperative antibiotic prophylaxis for acute calculous

    cholecystitis

    British Journal of Surgery, 2017

    19

    CHAPTER 3 The use of perioperative antibiotic prophylaxis in the

    treatment of acute cholecystitis (PEANUTS II trial): study

    protocol for a randomized controlled trial

    Accepted for publication in Trials (minor revisions)

    35

    CHAPTER 4 Conservative treatment of acute cholecystitis: a systematic

    review and pooled analysis

    Surgical endoscopy, 2017

    53

    CHAPTER 5 The optimal treatment of patients with mild and moderate

    acute cholecystitis: time for a revision of the Tokyo

    Guidelines

    Surgical Endoscopy, 2017

    73

    CHAPTER 6 Stand van Zaken: behandeling van cholecystitis acuta

    Accepted for publication in Nederlands Tijdschrift Voor

    Geneeskunde (minor revisions)

    87

    PART II MANAGEMENT OF HIGH-RISK PATIENTS WITH ACUTE

    CHOLECYSTITIS

    CHAPTER 7 Acute cholecystitis in elderly patients: a case for early

    cholecystectomy

    Journal of visceral surgery, 2017

    103

    https://www-ncbi-nlm-nih-gov.proxy.library.uu.nl/pubmed/28121041 https://www-ncbi-nlm-nih-gov.proxy.library.uu.nl/pubmed/28121041 https://www-ncbi-nlm-nih-gov.proxy.library.uu.nl/pubmed/28121041 https://www-ncbi-nlm-nih-gov.proxy.library.uu.nl/pubmed/27317033 https://www-ncbi-nlm-nih-gov.proxy.library.uu.nl/pubmed/27317033 https://www-ncbi-nlm-nih-gov.proxy.library.uu.nl/pubmed/28127715 https://www-ncbi-nlm-nih-gov.proxy.library.uu.nl/pubmed/28127715 https://www-ncbi-nlm-nih-gov.proxy.library.uu.nl/pubmed/28127715

  • OPTIMAL TREATMENT OF ACUTE CHOLECYSTITIS 7

    CHAPTER 8 Early cholecystectomy for acute cholecystitis in the elderly

    population: a systematic review and meta-analysis

    Digestive surgery, 2017

    115

    CHAPTER 9 Laparoscopic cholecystectomy versus percutaneous catheter

    drainage for acute calculous cholecystitis in high-risk patients

    Submitted

    133

    PART III SURGICAL TREATMENT OF COMMON BILE DUCT

    STONES

    CHAPTER 10 Surgical treatment of common bile duct stones

    Gallstones: recent advance in epidemiology, pathogenesis,

    diagnosis and management (book), 2016

    163

    CHAPTER 11 Summary and general discussion

    191

    APPENDICES

    Dutch Summary (Nederlandse samenvatting) 202

    Review Committee 209

    Authors and affiliations 210

    Acknowledgements (dankwoord) 213

    Curriculum Vitae 215

    https://www-ncbi-nlm-nih-gov.proxy.library.uu.nl/pubmed/28095385 https://www-ncbi-nlm-nih-gov.proxy.library.uu.nl/pubmed/28095385

  • CHAPTER 1

    General introduction

    and thesis outline

  • CHAPTER 1

    10 OPTIMAL TREATMENT OF ACUTE CHOLECYSTITIS

    INTRODUCTION

    Acute cholecystitis is a common indication for hospital admission and an increasing

    burden on the Western health care system. More than 90% of cases of acute cholecystitis

    are associated with cholelithiasis; a condition that afflicts at least 10% of the people in

    Western countries. 1 The prevalence of gallstones increases with age; in patients aged ≥ 60

    the prevalence rate ranges from 20% to 30% 2,3

    and increases to 80% in institutionalized

    individuals aged ≥ 90. 4

    The key element in the pathogenesis of acute calculous cholecystitis seems to be an

    obstruction of the cystic duct in the presence of bile supersaturated with cholesterol. 4

    Brief impaction may cause pain only, whereas prolonged impaction can result in

    inflammation. With inflammation, the gallbladder becomes enlarged and tense, and wall

    thickening and an exudate of pericholecystic fluid may develop. 5 While in most cases the

    inflammation initially is sterile, secondary infection occurs in approximately 30-50% of

    the patients, 6 most commonly caused by E. coli and K. pneumoniae. Bacterial

    superinfection with gas-forming organisms may lead to gas in the wall or lumen of the

    gallbladder (emphysematous cholecystitis). The wall of the gallbladder may undergo

    necrosis and gangrene (gangrenous cholecystitis). Without appropriate treatment, the

    gallbladder may perforate, leading to the development of an abscess or generalized

    peritonitis. 5

    Acute cholecystitis usually starts with an attack of biliary colic, often in a patient who had

    previous attacks. The pain persists and localizes in the right upper quadrant. Besides a

    positive Murphy’s sign and tenderness in the right upper quadrant, also fever and

    elevation in the white blood cell count are classically described. 7 According to the

    international guidelines for the management of acute cholecystitis, the "Tokyo

    guidelines", acute cholecystitis is clinically suspected if at least one local sign of

    inflammation (Murphy’s sign or pain, tenderness or mass in the right upper quadrant) and

    one sign of systematic inflammation (fever, leucocytosis, elevated C-reactive protein

    level) is present. 8 Only if confirmed by imaging, the diagnosis is definitive. Several

    imaging modalities can be used. Ultrasonography is usually favoured as the first test

    because it is relatively inexpensive and widely available, it involves no radiation exposure

    and has high sensitivity and specificity (81% and 83%, respectively). 9 Typical diagnostic

    findings include thickening of the gallbladder wall, presence of pericholecystic fluids and

    a sonographic Murphy’s sign. Scintigraphy and CT-tomography are usually reserved for

  • GENERAL INTRODUTION AND THESIS OUTLINE

    OPTIMAL TREATMENT OF ACUTE CHOLECYSTITIS 11

    patients in whom the diagnosis after ultrasonography is unclear or in patients suspected of

    complications. 10

    The severity of acute cholecystitis varies widely among patients. According to the Tokyo

    Guidelines, the severity is divided in three grades based on the degree of local and

    systemic inflammation and the presence of organ dysfunction. 8 Mild (grade I) acute

    cholecystitis is defined as acute cholecystitis in a healthy patient with no organ

    dysfunction and mild inflammatory changes in the gallbladder. Moderate (grade II) acute

    cholecystitis is defined as acute cholecystitis associated with any of the following

    conditions: elevated white blood cell count (>18.000/mm3), palpable tender mass in the

    right upper abdominal quadrant, duration of complaints > 72 hours, or marked local

    inflammation (gangrenous cholecystitis, pericholecystic abscess, hepatic abscess, biliary

    peritonitis, emphysematous cholecystitis). Severe (grade III) acute cholecystitis is defined

    as acute cholecystitis associated with organ dysfunction. The definition and grading as

    proposed by the Tokyo Guidelines are adapted in the Dutch Guidelines for the treatment

    of gallstone related disease. 11

    Laparoscopic cholecystectomy is the gold standard treatment of acute cholecystitis. This

    procedure can be performed either at the time of the initial attack (early cholecystectomy)

    or several weeks after the initial attack has subsided (delayed cholecystectomy). In the

    latter case, during the acute phase patients are treated with intraven