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The follow-up and results of laparoscopic

antireflux surgery

Jan Harm Koetje

The follow-up and results of

laparoscopic antireflux surgery

Jan Harm Koetje2016

The follow-up and results of laparoscopic antireflux surgeryKoetje, J.H. (Jan)

ISBN: 978-90-367-9197-7ISBN E-book: 978-90-367-9196-0

Thesis, University of Groningen, The Netherlands

Financial support for printing this thesis was kindly provided by: Erbe BV Nederland, Rijksuniversiteit Groningen, University Medical Center Groningen, ZWIK, Vakgroep Chirurgie Isala, De Research Manager, ChipSoft BV, 11-48 Dental Wellness

Cover design: J.H. KoetjeLayout: J.H. KoetjePrinted by: Gildeprint

© 2016 - Jan Harm Koetje - The Netherlands

All rights reserved. No part of this thesis may be reproduced, stored in a retrieval system or transmitted in any form or by any means, without prior permission of the author.

The follow-up and results of laparoscopic antireflux surgery

Proefschrift

ter verkrijging van de graad van doctor aan deRijksuniversiteit Groningen

op gezag van derector magnificus prof. dr. E. Sterken

en volgens besluit van het College voor Promoties.

De openbare verdediging zal plaatsvinden op

woensdag 16 november 2016 om 16.15 uur

door

Jan Harm Koetje

geboren op 15 juli 1988te Winschoten

PromotorProf. dr. G.M. van Dam

CopromotorDr. V.B. Nieuwenhuijs

BeoordelingscommissieProf. dr. D.I. Watson Prof. dr. M.P. Schijven Prof. dr. J.H. Kleibeuker

ParanimfenJart OosterhavenFloris Poelmann

To Nissen my tummy, the world my tongueAlbert Einstein to dr. Rudolf Nissen

Contents

Chapter 1: General introduction

Chapter 2: Double-blind randomised clinical trial of laparoscopic Toupet versus 180º anterior fundoplication for gastro-oesophageal reflux disease Accepted British Journal of Surgery

Chapter 3: Equal patient satisfaction, quality of life and objective recurrence rate after laparoscopic hiatal hernia repair with and without mesh Accepted Surgical Endoscopy

Chapter 4: Quality of life following repair of large hiatal hernia is improved but not influenced by use of mesh: results from a randomised controlled clinical trial World Journal of Surgery 2015

Chapter 5: Laparoscopic repair of hiatal hernia repair in the elderly patient World Journal of Surgery 2016

Chapter 6: Measuring outcomes of laparoscopic antireflux surgery: quality of life versus symptom scores? World Journal of Surgery 2016

Chapter 7: Online collection of PROM’s: an effective method for follow-up of benign surgery Submitted for publication

Chapter 8: Laparoscopic antireflux surgery as an effective treatment for chronic cough Submitted for publication

Chapter 9: Summary, general discussion, and final conclusions

Chapter 10: Summary in Dutch – Nederlandse samenvatting

Appendices: List of abbreviations Questionnaires List of publications

Acknowledgements – Dankwoord

Curriculum vitae auctoris

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1General introduction

13

General introduction

1

INTRODUCTIONThe introduction of laparoscopy in antireflux surgery caused a revival in the surgical treatment of gastro-

oesofageal reflux disease and symptomatic hiatal hernia. While open antireflux surgery was reserved as a last

resort for the patients that suffered severe reflux or had serious complications, laparoscopy made antireflux

surgery more acceptable because of less morbidity and faster recovery after the operation. This minimal

invasive approach showed equal effectiveness, which made it an appropriate treatment in an earlier stage of

disease. Therefore, laparoscopic antireflux surgery (LARS) quickly gained momentum as an applicable

treatment for moderate to severe reflux disease.1-3 It has become standard clinical practice and nowadays

LARS is the treatment of choice for patients who do not respond to medical therapy with acid suppression,

together with patients that suffer non-acid reflux, have extra-oesophageal complaints, and the patients who

are not willing to take lifelong medication.4-7 Despite the extensive research in LARS the last decades, there

are still questions that need to be answered. This thesis focuses on the follow-up and results of antireflux

surgery and tries to extend the knowledge that is gained so far. The following questions are adressed:

•• What is the best fundoplication?

•• Is laparoscopic hiatal hernia repair with and without mesh save and effective?

•• What is the appropriate method of follow-up for patients following laparoscopic antireflux

surgery?

•• Do patients suffering from chronic cough benefit from laparoscopic antireflux surgery?

GASTRO-OESOPHAGEAL REFLUX DISEASEGastro-oesophageal reflux disease (GORD) is a common chronic disease with increasing incidence in

Western countries, affecting around 40% of the population monthly, 20% weekly, and 7% daily.8,9 Heartburn

and regurgitation are the most frequent symptoms of GORD. Excessive reflux of gastric content (including

acid and activated pepsin) causes damage of oesophageal squamous mucosa.10,11 The pathogenesis of GORD

is complex and multifactorial. Overall, the disbalance originating from the failure of antireflux barriers

combined with oesophageal and gastric factors, causes GORD.12,13 Antireflux barriers include the intrinsic

lower oesophageal sphincter (LOS, the main component that is tonically contracted in rest, as the intrinsic

sphincter), the diaphragmatic crura (with extrinsic pressure of the LOS in rest and with increasing

compression of the LOS during increasing intra-abdominal pressure, as the extrinsic sphincter), the phreno-

oesophageal ligaments (that secures the LOS at the oesophageal hiatus of the diaphragm), and the angle of

His (forming a flap-valve effect).14-16 Aside from the prevention of excessive reflux, these antireflux barriers,

located at the gastro-oesophageal junction (GOJ), are important for allowing substances to pass through the

oesophagus to the stomach. This is achieved by swallow-induced LOS relaxations (SI-LOSR’s).17,18 Transient

LOS relaxations (TLOSR’s) provide the mechanism of belching. These relaxations are not combined with

oesophageal peristalsis, the TLOSR’s persist longer than SI-LOSR’s, and they are accompanied by

inhibition of the diaphragm.19,20 GORD is the result of excessive reflux and is caused in three different ways.

An increased number of TLOSR’s (stimulated by distention of the stomach, fat, stress, and subtreshold

stimulation of the pharynx) is one of the pathophysiologic mechanisms that cause disbalance at the GOJ

14

Chapter 1

and therefore excessive reflux. TLOSR’s are present in 80-100% of reflux episodes.12,21,22 Another important

mechanism of GORD is the hypotensive LOS pressure (HLOSP), that either causes reflux provoked by strain

(when intra-abdominal pressure exceeds the LOS pressure) or ‘free reflux’ (when there is a constant HLOSP

that is lower than intra-abdominal pressure).21,23,24 The third mechanism is weakening of the phreno-

oesophageal ligaments, creating a sliding hiatal hernia with displacement of the LOS to the intrathoracic

cavity. In Hiatal hernia the extrinsic compression of the diaphragm to the LOS is missing. Therefore, this

insufficient antireflux barrier causes reflux as well. 25,26 Delayed oesophageal volume and acid clearance is

accompanied with more oesophageal damage by refluxate.12 Delayed gastric emptying may increase the

number of TLOSR’s.27-30

LAPAROSCOPIC ANTIREFLUX SURGERYOpen antireflux surgery was the only effective treatment for reflux until proper acid suppressors were

introduced. Proton pump inhibitors (PPI’s) became the standard medical therapy in GORD, because it lead

to long term reflux control in 95% of the patients, had a low price and few side-effects.31-33 Despite these

good results, 5% of the patients do not benefit from PPI’s. For this group, along with patients that suffer from

non-acid (bile) reflux, patients with extra-oesophageal symptoms (like cough, hoarseness or dental erosion),

and patients that are unwilling to take lifelong medication, surgery is indicated. Laparoscopic

fundoplication demonstrated better relieve of GORD symptoms compared to PPI’s.34-36 Fundoplication is

the surgical antireflux treatment of choice, since it reconstructs an effective antireflux valve at the GOJ, works

for non-acid reflux and can cure GORD, in contrast to treatment with medicines.37,38 The first fundoplication

was described by dr. Rudolph Nissen in 1956.39 In the ‘Schweizer Medizinische Wochenschrift’ he calls this

technique, a procedure in which the fundus is wrapped around the oesophagus for 360º, a ‘simple operation

to control reflux oesophagitis’. It was the most frequently performed type of fundoplication until 2010.5 In

1991 Dallemagne reported the first laparoscopic Nissen fundoplication (LNF).40 It demonstrated comparable

effectiveness to the open Nissen fundoplication, but less morbidity. This caused increasing interest in surgical

treatment of GORD.

The Nissen fundoplication was associated with a serious incidence of postfundoplication symptoms, like

dysphagia, bloating, flatulence, and inability to belch.41-43 With the aim to reduce these postfundoplication

symptoms, Toupet developed a partial posterior fundoplication and Dor developed a partial anterior

fundoplication.44,45 These procedures were modified for laparoscopy and eventually the best partial

fundoplication were the 180º anterior fundoplication and 270º posterior fundoplication.46,47 Reflux control

on long term was similar with both the 180º anterior laparoscopic fundoplication (180ºLAF) and the

laparoscopic 270º posterior Toupet fundoplication (LTF) compared to the LNF, but less postfundoplication

symptoms were demonstrated with the partial fundoplications in several studies,48-53 randomised trials,50,54-65

and systematic reviews.42,43,47,66 Whether 180ºLAF or LTF provides the best reflux control combined with

minimal postfundoplication symptoms remains unclear.66,67 A recent randomised clinical trial aimed to com-

pare 180ºLAF and LTF but failed to include enough patients, and therefore underpowered results were

presented.68 In CHAPTER 2 the results of the MANTA-trial are described. This double-blind randomised

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1

clinical trial compares the 180ºLAF with the LTF, with the goal to determine which procedure provides the

most effective reflux control with the least postfundoplication side effects.

HIATAL HERNIA REPAIRHiatal hernias can be categorised in four types.69 Laparoscopic repair of symptomatic large hiatal hernias

(type II-IV) covered around 50% of laparoscopic antireflux procedures in the last decade.3 Laparoscopic

repair became standard therapy for patients with symptomatic large hiatal hernia. Surgical correction is the

only therapy that can be curative for these patients and it consists of dissection of the hernial sac from the

mediastinum into the abdomen, followed by cruroplasty with sutures and fundoplication.70 Additional partial

fundoplication is recommended, given the frequent reflux-symptoms and the risk of inducing pathologic

oesophageal acid exposure and oesophagitis.70-72 Different types of mesh were used to reinforce the

cruraplasty in attempt to reduce recurrence rates, with promising results in the first clinical trials.73-77 But use

of mesh was associated with serious complications (like oesophageal stenosis and erosion of the mesh into

the oesophagus) that could result in partial or total gastrectomy or even oesophagectomy.78-81 Studies with

objective outcome measures demonstrated that there is still doubt about routinely use of mesh in large hiatal

hernia repair.82,83 Only few studies describe the results of health-related QoL questionnaires as outcome,

although this might be more important for follow-up than radiologic follow-up.77 In CHAPTER 3 the results

of a cohort of patients after laparoscopic hiatal hernia correction are presented. Symptomatic outcome

measures using health-related QoL questionnaires, radiologic recurrence, symptomatic recurrence, and

reoperation rate are compared between primary cruraplasty and cruraplasty reinforced with mesh.

CHAPTER 4 describes the patient reported outcome of a randomised controlled trial that compared

primary cruraplasty, use of biologic absorbable mesh, and prosthetic non-absorbable mesh.

Hiatal hernia is more common in the elderly patient, with increasing incidence with age.84,85 It is likely that

more elderly patients with a large hiatal hernia will be referred to the surgeon. The results of our study that

addresses the risk of morbidity and mortality after hiatal hernia repair in the elderly patient are described in

CHAPTER 5.

PATIENT REPORTED OUTCOME MEASURESObjective measurements such as upper gastrointestinal endoscopy and 24-hour oesophageal pH test are

invasive and therefore poorly tolerated by patients. For that reason, these invasive techniques are less suit-

able to assess the effect of antireflux surgery over a longer period of time. Standardised symptom scores

and quality of life measures are more acceptable to patients and can be used repeatedly to assess outcome

at different time points, with high levels of compliance.59,86 Quality of care through the eyes of the patient

is considered as a better outcome measure for medical treatment, and has a different perception than the

professionally defined quality measures.87,88 This can be measured with Patient Reported Outcome Measures

(PROM’s). PROM’s are important for assessing quality of care and outcome of treatments in the perspective

of what the therapy really meant for the patient.89,90 PROM’s are reported by the patient and not influenced

by a researcher or clinician.91 PROM’s can consist symptom assessment and patient satisfaction scores by

using Likert or Visual Analog Scales, but can comprise specific validated quality of life (QoL)

16

Chapter 1

questionnaires as well. QoL includes a physical, psychological and social dimension. As a chronic disease

affecting all three dimensions, GORD has a great impact on QoL.92-94 In evaluating the outcome of LARS,

QoL should therefore be used as an outcome. As a secondary outcome, QoL was reported to improve

following LARS,95-98 but only a few studies used QoL as a primary outcome to compare different surgical

techniques or medical treatment versus surgical treatment.49,51,52,98,99 Both generic and disease-specific

questionnaires are being developed, to make QoL somehow quantitative and comparable for use in

research.100 Whether the generic QoL questionnaires, health-related QoL questionnaires or symptom scores

are most effective for follow-up after LARS remains uncertain. CHAPTER 6 describes the results of a

correlation study that compares the generic SF-36 questionnaire with symptom scores, patient satisfaction

and the ‘gastro-esophaeal reflux disease health-related quality of life questionnaire’ (GERD-hr-QoL).

Complete data is important for reliable and representative results. To gain high response rates and complete

data during follow-up, several data collection methods were used, with varying results.101-105 Since many

people have access to the internet nowadays, using it for follow-up is likely. Response rates and

completeness rates of our cohort of patients following LARS using an online data collection system are

described in CHAPTER 7.

GASTRO-OESOPHAGEAL REFLUX INDUCED CHRONIC COUGHSelection of patients for antireflux surgery does not require objective evidence of GORD. Patients with

negative 24-hour opesophageal pH test or negative endoscopy could still benefit from laparoscopic

fundoplication if they have typical reflux symptoms.106,107 Watson described that patients considered for

surgery can usually be categorised as either (I) failing to respond fully to medical therapy, or (II) unwilling

to take lifelong medication, despite full response to medication.2 Extra-oesophageal symptoms like chronic

cough could also be caused by GORD and are also reason for LARS.108-111 In up to 41% of the patients

suffering from chronic cough it is caused by GORD.112 LARS for this so-called gastro-oesophageal reflux

induced chronic cough (GORC) was believed to show poor results. Varying outcomes were described by

several studies.113-121 However, the majority of this studies included patients with typical GORD symptoms as

their main complaint. Airway symptoms were additional complaints. Only three papers described a positive

outcome for LNF as a treatment for cough as primary complaint.116,117,121 Use of a partial fundoplication and

evaluation using PROM’s is not described. CHAPTER 8 describes a cohort of 50 patients, who underwent

partial fundoplication for chronic cough as their main complaint, using PROM’s as primary outcome

measure. We hypothesised that LARS was an effective treatment for these patient.

THIS THESIS STUDIES THE FOLLOW-UP AND RESULST OF LAPAROSCOPIC ANTIREFLUX

SURGERY.

It discusses how results of laparoscopic antireflux surgery should be measured. The following chapters also

address which type of partial fundoplication should be used, whether the use of mesh in hiatal hernia is save

and whether the use of mesh is required. The safety of laparoscopic hiatal hernia repair in elderly and

laparoscopic antireflux surgery as treatment for chronic cough are evaluated.

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62. Mardani J, Lundell L, Engstrom C. Total or posterior partial fundoplication in the treatment of GERD: results of a randomized trial after 2 decades of follow-up. Ann Surg 2011 May;253(5):875-878.63. Raue W, Ordemann J, Jacobi CA, Menenakos C, Buchholz A, Hartmann J. Nissen versus Dor fundoplication for treatment

of gastroesophageal reflux disease: a blinded randomized clinical trial. Dig Surg 2011;28(1):80-86.64. Koch OO, Kaindlstorfer A, Antoniou SA, Asche KU, Granderath FA, Pointner R. Laparoscopic Nissen versus Toupet fundoplication: objective and subjective results of a prospective randomized trial. Surg Endosc 2012 Feb;26(2):413-422.65. Mickevicius A, Endzinas Z, Kiudelis M, Jonaitis L, Kupcinskas L, Pundzius J, et al. Influence of wrap length on the effectiveness of Nissen and Toupet fundoplications: 5-year results of prospective, randomized study. Surg Endosc 2013

Mar;27(3):986-991.66. Stefanidis D, Hope WW, Kohn GP, Reardon PR, Richardson WS, Fanelli RD, et al. Guidelines for surgical treatment of

gastroesophageal reflux disease. Surg Endosc 2010 Nov;24(11):2647-2669.67. Thompson SK, Watson DI. What is the best anti-reflux operation? All fundoplications are not created equal. World J Surg

2015 Apr;39(4):997-999.68. Daud WN, Thompson SK, Jamieson GG, Devitt PG, Martin IJ, Watson DI. Randomized controlled trial of laparoscopic

anterior 180 degrees partial versus posterior 270 degrees partial fundoplication. ANZ J Surg 2015 Sep;85(9):668-672.69. Kohn GP, Price RR, Demeester SR, Zehetner J, Muensterer OJ, Awad ZT, et al. Guidelines for the Management of Hiatal

Hernia - A SAGES guideline. 2013; Available at: http://www.sages.org/publications/guidelines/guidelines-for-the- management-of-hiatal-hernia. Accessed 06/15, 2016.70. Wijnhoven BP, Watson DI. Laparoscopic repair of a giant hiatus hernia--how I do it. J Gastrointest Surg 2008

Aug;12(8):1459-1464.71. Watson DI, Davies N, Devitt PG, Jamieson GG. Importance of dissection of the hernial sac in laparoscopic surgery for large

hiatal hernias. Arch Surg 1999 Oct;134(10):1069-1073.72. Furnee EJ, Draaisma WA, Gooszen HG, Hazebroek EJ, Smout AJ, Broeders IA. Tailored or routine addition of an antireflux

fundoplication in laparoscopic large hiatal hernia repair: a comparative cohort study. World J Surg 2011 Jan;35(1):78-84.73. Carlson MA, Richards CG, Frantzides CT. Laparoscopic prosthetic reinforcement of hiatal herniorrhaphy. Dig Surg

1999;16(5):407-410.74. Frantzides CT, Madan AK, Carlson MA, Stavropoulos GP. A prospective, randomized trial of laparoscopic polytetrafluoro-

ethylene (PTFE) patch repair vs simple cruroplasty for large hiatal hernia. Arch Surg 2002 Jun;137(6):649-652.75. Granderath FA, Schweiger UM, Kamolz T, Asche KU, Pointner R. Laparoscopic Nissen fundoplication with prosthetic hiatal

closure reduces postoperative intrathoracic wrap herniation: preliminary results of a prospective randomized functional and clinical study. Arch Surg 2005 Jan;140(1):40-48.

76. Oelschlager BK, Pellegrini CA, Hunter J, Soper N, Brunt M, Sheppard B, et al. Biologic prosthesis reduces recurrence after laparoscopic paraesophageal hernia repair: a multicenter, prospective, randomized trial. Ann Surg 2006 Oct;244(4):

481-490.77. Oelschlager BK, Pellegrini CA, Hunter JG, Brunt ML, Soper NJ, Sheppard BC, et al. Biologic prosthesis to prevent recurrence after laparoscopic paraesophageal hernia repair: long-term follow-up from a multicenter, prospective, randomized trial. J Am Coll Surg 2011 Oct;213(4):461-468.78. Tatum RP, Shalhub S, Oelschlager BK, Pellegrini CA. Complications of PTFE mesh at the diaphragmatic hiatus. J Gastrointest Surg 2008 May;12(5):953-957.

20

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79. Stadlhuber RJ, Sherif AE, Mittal SK, Fitzgibbons RJ,Jr, Michael Brunt L, Hunter JG, et al. Mesh complications after prosthetic reinforcement of hiatal closure: a 28-case series. Surg Endosc 2009 Jun;23(6):1219-1226.

80. Hazebroek EJ, Leibman S, Smith GS. Erosion of a composite PTFE/ePTFE mesh after hiatal hernia repair. Surg Laparosc Endosc Percutan Tech 2009 Apr;19(2):175-177.

81. Frantzides CT, Carlson MA, Loizides S, Papafili A, Luu M, Roberts J, et al. Hiatal hernia repair with mesh: a survey of SAGES members. Surg Endosc 2010 May;24(5):1017-1024.

82. Memon MA, Memon B, Yunus RM, Khan S. Suture Cruroplasty Versus Prosthetic Hiatal Herniorrhaphy for Large Hiatal Hernia: A Meta-analysis and Systematic Review of Randomized Controlled Trials. Ann Surg 2016 Feb;263(2):258-266.

83. Tam V, Winger DG, Nason KS. A systematic review and meta-analysis of mesh vs suture cruroplasty in laparoscopic large hiatal hernia repair. Am J Surg 2016 Jan;211(1):226-238.

84. Lal DR, Pellegrini CA, Oelschlager BK. Laparoscopic repair of paraesophageal hernia. Surg Clin North Am 2005 Feb;85(1):105-18, x.

85. Grotenhuis BA, Wijnhoven BP, Bessell JR, Watson DI. Laparoscopic antireflux surgery in the elderly. Surg Endosc 2008 Aug;22(8):1807-1812.

86. Yang H, Watson DI, Lally CJ, Devitt PG, Game PA, Jamieson GG. Randomized trial of division versus nondivision of the short gastric vessels during laparoscopic Nissen fundoplication: 10-year outcomes. Ann Surg 2008 Jan;247(1):38-42.

87. Patrick D.L. BM. Measurement of health status in the 1990s. Annu Rev Public Health 1990;11:165-183.88. Garratt A, Schmidt L, Mackintosh A, Fitzpatrick R. Quality of life measurement: bibliographic study of patient assessed

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92. Dimenas E, Glise H, Hallerback B, Hernqvist H, Svedlund J, Wiklund I. Well-being and gastrointestinal symptoms among patients referred to endoscopy owing to suspected duodenal ulcer. Scand J Gastroenterol 1995 Nov;30(11):1046-1052.

93. Revicki DA, Wood M, Maton PN, Sorensen S. The impact of gastroesophageal reflux disease on health-related quality of life. Am J Med 1998 Mar;104(3):252-258.

94. Kamolz T, Pointner R, Velanovich V. The impact of gastroesophageal reflux disease on quality of life. Surg Endosc 2003 Aug;17(8):1193-1199.

95. Glise H, Hallerback B, Johansson B. Quality-of-life assessments in evaluation of laparoscopic Rosetti fundoplication. Surg Endosc 1995 Feb;9(2):183-8; discussion 188-9.

96. Hunter JG, Trus TL, Branum GD, Waring JP, Wood WC. A physiologic approach to laparoscopic fundoplication for gastro-esophageal reflux disease. Ann Surg 1996 Jun;223(6):673-85; discussion 685-7.

97. Kamolz T, Wykypiel H,Jr, Bammer T, Pointner R. Quality of life after laparoscopic antireflux surgery--Nissen fundoplication. Chirurg 1998 Sep;69(9):947-950.

98. Granderath FA, Kamolz T, Schweiger UM, Pointner R. Quality of life, surgical outcome, and patient satisfaction three years after laparoscopic Nissen fundoplication. World J Surg 2002 Oct;26(10):1234-1238.

99. Zugel N, Jung C, Bruer C, Sommer P, Breitschaft K. A comparison of laparoscopic Toupet versus Nissen fundoplication in gastroesophageal reflux disease. Langenbecks Arch Surg 2002 Jan;386(7):494-498.

100. Ware JE,Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992 Jun;30(6):473-483.101. Kleinman L, Leidy NK, Crawley J, Bonomi A, Schoenfeld P. A comparative trial of paper-and-pencil versus computer administration of the Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire. Med Care 2001 Feb;39(2): 181-189.102. Bushnell DM, Martin ML, Parasuraman B. Electronic versus paper questionnaires: a further comparison in persons with

asthma. J Asthma 2003;40(7):751-762.103. Marks RG. Validating electronic source data in clinical trials. Control Clin Trials 2004 Oct;25(5):437-446.104. Bushnell DM, Reilly MC, Galani C, Martin ML, Ricci JF, Patrick DL, et al. Validation of electronic data capture of the Irritable

Bowel Syndrome--Quality of Life Measure, the Work Productivity and Activity Impairment Questionnaire for Irritable Bowel Syndrome and the EuroQol. Value Health 2006 Mar-Apr;9(2):98-105.

105. Welker JA. Implementation of electronic data capture systems: barriers and solutions. Contemp Clin Trials 2007 May;28(3):329-336.

106. Booth MI, Stratford J, Thompson E, Dehn TC. Laparoscopic antireflux surgery in the treatment of the acid-sensitive oesophagus. Br J Surg 2001 Apr;88(4):577-582.

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107. Leeder PC, Watson DI, Jamieson GG. Laparoscopic fundoplication for patients with symptoms but no objective evidence of gastroesophageal reflux. Dis Esophagus 2002;15(4):309-314.

108. Napierkowski J, Wong RK. Extraesophageal manifestations of GERD. Am J Med Sci 2003 Nov;326(5):285-299.109. Irwin RS. Chronic cough due to gastroesophageal reflux disease: ACCP evidence-based clinical practice guidelines. Chest

2006 Jan;129(1 Suppl):80S-94S.110. Blondeau K, Dupont LJ, Mertens V, Tack J, Sifrim D. Improved diagnosis of gastro-oesophageal reflux in patients with unexplained chronic cough. Aliment Pharmacol Ther 2007 Mar 15;25(6):723-732.111. Farrokhi F, Vaezi MF. Extra-esophageal manifestations of gastroesophageal reflux. Oral Dis 2007 Jul;13(4):349-359.112. Morice AH, Kastelik JA. Cough. 1: Chronic cough in adults. Thorax 2003 Oct;58(10):901-907.113. Johnson WE, Hagen JA, DeMeester TR, Kauer WK, Ritter MP, Peters JH, et al. Outcome of respiratory symptoms after

antireflux surgery on patients with gastroesophageal reflux disease. Arch Surg 1996 May;131(5):489-492.114. Chen RY, Thomas RJ. Results of laparoscopic fundoplication where atypical symptoms coexist with oesophageal reflux.

Aust N Z J Surg 2000 Dec;70(12):840-842.115. Farrell TM, Richardson WS, Trus TL, Smith CD, Hunter JG. Response of atypical symptoms of gastro-oesophageal reflux to

antireflux surgery. Br J Surg 2001 Dec;88(12):1649-1652.116. Novitsky YW, Zawacki JK, Irwin RS, French CT, Hussey VM, Callery MP. Chronic cough due to gastroesophageal reflux

disease: efficacy of antireflux surgery. Surg Endosc 2002 Apr;16(4):567-571.117. Allen CJ, Anvari M. Does laparoscopic fundoplication provide long-term control of gastroesophageal reflux related cough?

Surg Endosc 2004 Apr;18(4):633-637.118. Kaufman JA, Houghland JE, Quiroga E, Cahill M, Pellegrini CA, Oelschlager BK. Long-term outcomes of laparoscopic antireflux surgery for gastroesophageal reflux disease (GERD)-related airway disorder. Surg Endosc 2006

Dec;20(12):1824-1830.119. Brown SR, Gyawali CP, Melman L, Jenkins ED, Bader J, Frisella MM, et al. Clinical outcomes of atypical extra-esophageal

reflux symptoms following laparoscopic antireflux surgery. Surg Endosc 2011 Dec;25(12):3852-3858.120. Ratnasingam D, Irvine T, Thompson SK, Watson DI. Laparoscopic antireflux surgery in patients with throat symptoms: a

word of caution. World J Surg 2011 Feb;35(2):342-348.121. Faruqi S, Sedman P, Jackson W, Molyneux I, Morice AH. Fundoplication in chronic intractable cough. Cough 2012 Jul

19;8(1):3-9974-8-3.

2Double-blind randomised clinical trial of laparoscopic Toupet versus 180º anterior fundoplication for gastro-oesophageal reflux disease

Oral presentation at Chirurgendagen 2016, Veldhoven

Oral presentation at European Association of Endoscopic Surgery Congress 2016, Amsterdam

Oral presentation at ANZGOSA/SUGSS Conference 2016, Sydney, Australia

D.J. RoksJ.H. Koetje J.E. OorJ.A. BroedersV.B. NieuwenhuijsE.J. Hazebroek

Accepted in British Journal of Surgery

24

Chapter 2

ABSTRACT

BACKGROUND Meta-analyses have demonstrated that partial fundoplications provide similar reflux

control with less postfundoplication symptoms compared to Nissen fundoplication for

gastro-oesophageal reflux disease (GORD). It remains unclear which partial

fundoplication is surgical therapy of choice. Aim was to compare outcome of 270°

posterior laparoscopic Toupet (LFT) with 180° anterior fundoplication (180ºLAF).

METHODS A double-blind randomised clinical trial (RCT) was conducted between 2012 and

2015 in two hospitals specialised in antireflux surgery. Patients were randomised to

undergo primary LTF or 180ºLAF. Subjective outcome was analysed at one, three, six,

and 12 months following surgery. Objective reflux control was assessed before and three

months after surgery.

RESULTS 94 patients were randomised to LTF (n=47) or 180ºLAF (n=47). Subjective outcome at

12 months demonstrated no significant differences in control of reflux or post-

fundoplication symptoms, except for an increased prevalence of increased flatulence

and chest pain after LTF at one and six months respectively (71% vs. 49%, p=0.034;

23% vs. 7%, p=0.039). Furthermore, there were no significant differences in

satisfaction and willingness to undergo surgery again. Postoperative endoscopy and

24-hr pH-monitoring demonstrated no significant differences in mean oesophageal

acid exposure time or recurrent pathological oesophageal acid exposure.

CONCLUSIONS The results of this trial provide evidence for equal short-term outcomes of LTF and

180ºLAF as surgical procedures for GORD, with similar subjective and objective

reflux control, postfundoplication symptoms and patient satisfaction. The long-term

results of this RCT need to be awaited to evaluate whether differences develop with

extension of follow-up.

25

MANTA: Double-blind RCT of laparoscopic Toupet fundoplication versus 180º anterior fundoplication for GORD

2

INTRODUCTIONFor patients suffering from gastro-oesophageal reflux disease (GORD) who are not responding to medical

treatment or not willing to take life-long medication, laparoscopic fundoplication is currently considered the

treatment of choice.1,2 Previous studies have demonstrated comparable and durable subjective and objective

reflux control, with a lower risk for surgical reintervention after laparoscopic fundoplication compared to

open fundoplication.1,3 Until 2010, 360˚ posterior laparoscopic Nissen fundoplication (LNF) has been the

most frequently performed antireflux procedure.1,4,5 However, LNF is associated with a high incidence of

troublesome dysphagia and gas-related symptoms, like gas bloating, flatulence and inability to belch.6-8

Partial fundoplications have been developed as alternatives for LNF, with the aim to reduce the incidence

of these postfundoplication symptoms.6,9-15 The most commonly used partial fundoplications are posterior

270˚ Toupet fundoplication (LTF) and anterior 180˚ fundoplication(180˚ LAF).10,16

Several randomized clinical trials (RCTs)9,14,17-23 and meta-analyses6,10,24 have evaluated whether partial wraps

reduce postfundoplication symptoms and whether this is at the expense of inferior reflux control compared

to LNF.25 Both LTF6 and 180˚ LAF10 provide similar reflux control with a lower prevalence of postoperative

dysphagia and gas-related symptoms compared to LNF.6 However, it is unclear which of these two partial

fundoplications yields the best reflux control with minimal postoperative side effects. Currently, only two

trials have previously compared laparoscopic anterior and posterior partial fundoplication.26,27 The first trial

compared 120˚ anterior fundoplication to LTF and reported poor results after the anterior approach.

However, the technique applied in the anterior arm might be inferior to a wrap with 180˚ circumference.27

The second trial had identical surgical techniques to the current study but was underpowered.26 Therefore

the current trial was conducted to compare the anterior variant which seems to yield the best results with LTF.

The aim of the present study was to determine whether LTF or 180˚ LAF offers the best subjective and

objective reflux control, with the least postfundoplication symptoms.

METHODSThis multicenter double-blind randomized clinical trial compared two laparoscopic antireflux procedures:

270˚ posterior LTF28 and the 180˚ anterior partial LAF.29 Differences in short-term reflux control, post-

operative dysphagia and gas-related symptoms and patient satisfaction were examined using upper gastro-

intestinal endoscopy, oesophageal manometry and 24-hr pH-monitoring, and questionnaires. This trial was

designed in a similar fashion as the trial conducted in Australia.26

STUDY DESIGN

The study was performed as a multicenter trial in two large teaching hospitals in the Netherlands, with all

patients operated by one experienced (annual 60 fundoplications / year / surgeon; surgeon total case

load > 400) gastrointestinal surgeon per centre (VBN and EJH). Adult patients with GORD which was

objectively proven by either endoscopy and/or 24 hr oesophageal pH-monitoring and with an indication for

antireflux surgery, were considered eligible for inclusion. Patients who had undergone previous antireflux

surgery and/or suffered from a large hiatal hernia (more than 50% of the stomach in the chest), oesophageal

aperistalsis, spasms or achalasia were excluded.

26

Chapter 2

After informed consent, 1:1 randomization to LTF or 180˚ LAF was performed using web-based

randomisation. Only patients who were deemed to be suitable for both procedures were randomized. Pre-

operative workup was as per standard clinical practice, which included upper gastrointestinal endoscopy,

oesophageal manometry and 24-hr pH-monitoring. Oesophagitis was graded based upon the Los Angeles

classification.30 The pH electrode was positioned 5 cm above the manometrically determined upper margin

of the lower oesophageal sphincter. Preoperative barium swallows were only performed if clinically indicated,

given that barium swallows are insufficient as screening for GORD.31 Patients were not informed regarding the

type of fundoplication that was performed, and objective follow-up investigations were performed by a

blinded observer. Both hospitals had similar pre- and postoperative care and workup.

SURGICAL PROCEDURES

All fundoplications were performed using standardized laparoscopic techniques. Tutoring and a convention

meeting between the two participating surgeons ensured similar techniques in both participating hospitals.

In all instances, the procedure commenced with dissection of the lower oesophagus and routine posterior

hiatal repair using non-absorbable sutures. If present, the size and type of a hiatal hernia (HH) was assessed

by the surgeon and noted in the case record forms (CRF’s). LTF entailed the creation of a posterior partial

fundoplication of the gastric fundus, which was anchored to the oesophagus on the left and right sides, as

well as to the crus postero-laterally on the right side, while leaving the anterior oesophagus uncovered. When

constructing a 180˚ LAF, the ventral wall of the gastric fundus was sutured to the anterior oesophagus and

the right crus.32 If laparoscopy had to be converted to an open procedure, the patient remained included in

the study. If the performed fundoplication type was not consistent with the allocated fundoplication type, the

patient was not excluded and remained in the allocated group for intention-to-treat analysis.

POSTOPERATIVE CARE

Patients were allowed oral fluids directly, and soft solid food the next day. Early discharge from the hospital

was usual (day 1 or 2 postoperatively). Barium meal X-ray was not routinely performed before discharge.

POSTOPERATIVE FOLLOW-UP

Primary outcome of this trial was the difference in Dakkak dysphagia scores between the two study groups, as

assessed using validated questionnaires. Reflux control was assessed using upper gastrointestinal endoscopy

and oesophageal 24-hr pH-monitoring three months following surgery. All postoperative examinations were

performed by gastroenterologists with extensive expertise in antireflux surgery and the associated changes

in oesophagogastric anatomy. The presence of reflux, dysphagia and gas related symptoms was assessed at

one, three, six, and 12 months following surgery using standardized questionnaires. All patients were

interviewed preoperatively and received these standardized questionnaires through mail. If a patient did not

return these questionnaires within one month, telephone calls were used to remember the patient to

complete their questionnaires. The presence or absence of the following symptoms was determined:

heartburn, chest pain, epigastric pain, regurgitation, dysphagia, satiety, inability to belch, gas bloating,

anorexia, nausea, vomiting, nocturnal coughing, flatulence and diarrhea. Furthermore, the presence and

quantification of heartburn and dysphagia for liquids and solids was assessed using 0 to 10 visual analog

27


2

scales (0= no symptoms; 10=severe symptoms). The presence and quantification of dysphagia was further

examined using the validated Dakkak dysphagia score, addressing the difficulty (0= never; 1=sometimes,

2=always) of swallowing nine types of liquids and solids.33 Overall outcome of surgery was ranked using an

analog satisfaction score (0= dissatisfied, 10= satisfied), a modified Visick grading score34 (1= no symptoms,

5= worse symptoms following surgery), the question if patients would undergo surgery again (0=no, 1= yes),

and an overall outcome score (1= perfect; 4= bad outcome). Changes in the use of proton pump inhibitors

and histamine-2 blockers were also addressed.

SAMPLE SIZE CALCULATION AND STATISTICS

Sample size calculation was based on an estimated reduction in Dakkak dysphagia scores at 6 months of

follow-up. A previous study found a Dakkak dysphagia score of 7.0 following LTF.27 The aim was to reduce

this Dakkak dysphagia score by a clinically relevant 50% to 3.5 following 180 degrees anterior fundoplication

based on another clinical study that found a dysphagia score of 3.5 following 180 degrees anterior

fundoplication.35 A two sample T-test power analysis with a power of 0.8 and α of 0.05 was performed,

resulting in a sample size of 47 versus 47 (PASS 2008, version 8.0.8.). All data were entered in a

computerised database and analyzed using the statistical software package SPSS version 22.0 (SPSS, Inc.,

Chicago, IL, USA). All included patients were analyzed based on an intention-to-treat, with a separate

per-protocol analysis. No stratification analyses for centre were conducted. Data were expressed as mean (95%

confidence interval) or total number of patients (%), unless stated otherwise. The Chi square test, or Fisher’s

exact test where necessary, were used for comparing binary variables between groups, and the

Mann-Whitney U test for continues variables. The Wilcoxon signed rank test was used to determine

significant effects of surgery within either the LTF or the 180˚ LAF group. Statistical significance was defined

as p< 0.05. The protocol for this study was approved by the Medical Ethics Committees (METC) of the St.

Antonius Hospital, Nieuwegein and the Isala Clinics, Zwolle (RCT number NL39193.100.12). To guarantee

the safety and quality throughout the study an independent data safety monitoring board (DSMB) was

established which has monitored the trials quality and followed the occurrence of all patient safety related

endpoints. A safety analysis has been performed by the DSMB and reported to the METC when 50% of the

patients were included. This trial has been registered in the Netherlands Trial Register, number NTR5702

(www.trialregister.nl).

RESULTSBetween August 2012 and May 2015, a total of 94 patients were included (Figure 1). Forty-seven patients

were randomized to LTF and 47 to 180˚ LAF. Of the included 94 patients, 85 patients (90%) completed the

questionnaires at one month, 85 (90%) at three months, 85 patients (90%) at six months, and 85 patients

(90%) at 12 months following surgery. Objective follow-up data was available for 76 patients (81%).

CONSORT flow diagram of symptomatic and objective follow-up has been summarized in Figure 1. During

the 12 month follow-up period, one patient withdrew from the study. Missing symptomatic or objective

follow-up data was caused by patients being lost to follow-up or unwillingness of patients to complete

questionnaires or undergo postoperative investigations.

28

Chapter 2

SUBJECTS

The baseline characteristics of the included patients are summarized in Table 1, with no differences between

the two groups.

TABLE 1. BASELINE CHARACTERISTICS

LTF (n=47) 180ºLAF (n=47)

Sex (M/F) 24 / 23 23 / 24

Age (yr.) 48.8 (15.3) 53.3 (12.4)

BMI (kg/m2) 27.4 (5.0) 27.4 (4.0)

Duration of symptoms (yr.) 7.5 (7.4) 8.6 (7.8)

Previous surgery* 17 (36.2%) 22 (46.8%)

ASA-classification I 21 (44.7%) 14 (29.8%)

II 24 (51.1%) 27 (57.4%)

III 2 (4.3%) 3 (6.4%)

All data are expressed as mean (SD) or n (%); LTF (laparoscopic Toupet fundoplication); 180ºLAF (180º laparoscopic anterior fundoplication); *= History of thoracic or abdominal surgery other than antireflux surgery

159 patients assessed for eligibility

Randomisation

1 month follow-up

3 months follow-up

6 months follow-up

35 patients excluded:- not meeting inclusion criteria (n=4)- declined to participate (n=20)- language barrier (n=2)- combination with other surgical procedure (n=9)

159 patients assessed for eligibility

LTF (n=47) 180ºLAF(n=47)

41 (87%) completedquestionnaire


42 (89%) completedquestionnaire;1 patient end of trial;32 (68%) endoscopy23 (49%) manometry35 (75%) 24h-pH-metry

43 (92%) completedquestionnaire;

32 (68%) endoscopy28 (60%) manometry41 (87%) 24h-pH-metry





12 months follow-up

LTF (Laparoscopic Toupet fundoplication); 180ºLAF (180º Laparoscopic anterior fundoplication)

FIGURE 1. CONSORT DIAGRAM OF ENROLMENT AND FOLLOW-UP OF PATIENTS

29


2

PERIOPERATIVE OUTCOME

All of the 94 included patients underwent the allocated surgical treatment and there were no conversions to

open surgery. In none of the patients a bougie was used. Mean operating time did not significantly differ

between the two procedures (53 min. vs. 48 min., p=0.091, Table 2). A HH was present in 36 (77%) patients

in the LTF-group and 42 patients (89%) in the 180˚ LAF-group (p=0.251, Table 2). Cruroplasty using non-

absorbable sutures was performed in all patients, with posterior cruroplasty being performed in 22 (47%)

and 34 (72%) patients respectively, and posterior and anterior cruroplasty performed more frequently

after LTF, in 25 patients (53%) and 13 (28%) respectively (p=0.012, Table 2). None of the HH repairs was

performed using mesh. An intraoperative complication occurred in one patient in the 180˚ LAF-group

(p=1.000) and consisted of a diaphragmatic bleeding (blood loss 600cc). Postoperative complications

within 30 days following surgery occurred in three patients in the LTF-group, including acute dysphagia

(n=2) and acute obstruction based on food stasis (n=1), and one patient in the 180˚ LAF-group developed

gastroenteritis (6% vs. 2%, p=0.617). Revision fundoplication was performed in the two patients within the

LTF-group suffering from acute dysphagia at five and 14 days following primary surgery. In both patients the

LTF was converted to an 180˚ LAF without complications, after which the dysphagia resolved.

TABLE 2. PERIOPERATIVE OUTCOME

LTF (n=47) 180ºLAF (n=47) P-value

Hiatal hernia <10% 26 (55.3%) 28 (59.6%) 0.251

10-25% 10 (21.3%) 11 (23.4%)

25-49% 0 (0%) 2 (4.3%)

50-75% 0 (0%) 1 (2.1%)

Crural closure Posterior 22 (46.8%) 34 (72.3%) 0.012

Posterior + anterior 25 (53.2%) 13 (27.7%)

Procedure time (min) 52.9 (19) 47.7 (19) 0.091

Intraoperative complications 0 (0%) 1 (2.1%) 1.000

Postoperative complications within 30 days 3 (6.4%) 1 (2.1%) 0.617

Length of hospital stay 1.5 (1.1) 1.2 (0.6) 0.136

Need for surgical reintervention 2 (4.3%) 0 (0%) 0.495

All data are expressed as n (%) or mean (SD)LTF (laparoscopic Toupet fundoplication); 180ºLAF (180º laparoscopic anterior fundoplication)

SYMPTOMATIC OUTCOME

The preoperative symptom scores of both groups and symptomatic outcome up to 12 months following

surgery are summarized in Tables 3 to 5. Only increased flatulence (71% vs. 49%, p=0.034) and chest pain

(23% vs. 7%, p=0.039) were significantly more prevalent in the LTF-group compared to the 180˚ LAF-group

at one month and six months following surgery respectively (Table 3). In both groups there was a significant

decrease in mean visual analog scale score for heartburn at 12 months follow-up compared to the pre-

operative score (5.1 vs. 1.3, p=<0.001, LTF; 4.6 vs. 1.2, p=<0.001, 180˚ LAF). Mean heartburn-score between

the two groups was similar at one, three, six months and 12 months following surgery (p=0.759, Table 4).

30

Chapter 2

TABLE 3. PRE- AND POSTOPERATIVE SYMPTOMS

Preop 1 month postop 3 months postop 6 months postop 12 months postop

LTF LAF LTF LAF LTF LAF LTF LAF LTF LAF

Heartburn 93.6% 87.2% 20.0% 12.2% 25.6% 12.2% 7.0% 9.5% 20.9% 14.3%

Chest pain 66.0% 74.5% 35.6% 31.7% 30.2% 17.1% 23.3%|| 7.1%|| 16.3% 16.7%

Epigastric pain 48.9% 59.6% 53.3% 53.7% 32.6% 26.8% 25.6% 28.6% 16.3% 16.7%

Regurgitation 66.0% 78.7% 24.4% 24.4% 14.0% 22.0% 18.6% 16.7% 20.9% 16.7%

Pain during swallowing 6.4% 12.8% 15.6% 14.6% 9.3% 7.3% 2.3% 0.0% 7.0% 0.0%

Postprandial satiety 25.5% 38.3% 68.9% 63.4% 65.1% 51.2% 41.9% 31.0% 44.2% 26.2%

Inability to belch - - 20.0% 26.8% 9.3% 14.6% 7.0% 14.3% 14.0% 9.5%

Gas bloating 34.0% 38.3% 48.9% 43.9% 27.9% 31.7% 32.6% 33.3% 32.6% 26.2%

Anorexia 6.4% 8.5% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

Nausea 38.3% 29.8% 33.3% 26.8% 16.3% 17.1% 16.3% 23.8% 14.0% 9.5%

Vomiting 17.0% 31.9% 8.9% 17.1% 2.03% 2.4% 2.3% 2.4% 4.7% 0.0%

Nocturnal coughing 36.2% 25.5% 11.1% 17.1% 9.3% 12.2% 18.6% 9.8% 16.3% 7.1%

Increased flatulence - - 71.1%* 48.8%* 65.1% 61.0% 58.1% 63.4% 60.5% 50.2%

Diarrhea - - 15.6% 22.0% 23.3% 14.6% 14.0% 14.6% 11.6% 14.3%

Data are presented as n (%). All significant differences (p<0.05) are highlighted in bold. * p=0.034, || p=0.039LTF (laparoscopic Toupet fundoplication); LAF (180º laparoscopic anterior fundoplication)

TABLE 4. PRE- AND POSTOPERATIVE CONTROL OF HEARTBURN AND PRESENCE OF DYSPHAGIA



Control of heartburn 34.0% 23.4% 79.1% 89.7% 85.7% 86.8% 93.0% 92.7% 90.7% 90.2%

VAS for heartburn

Mean 5.0 4.6 2.0 1.6 1.6 2.0 1.1 1.4 1.3 1.2

95% CI 4.1-6.0 3.7-5.1 1.1-2.8 0.7-2.5

0.8-2.3 1.0-2.9 0.6-1.7 0.7-2.0 0.8-1.8 0.6-1.7

Presence of dysphagia 34.0% 38.3% 55.6% 41.5% 23.8% 22.0% 16.7% 23.8% 16.3% 16.7%

VAS for liquids

Mean 0.8 1.0 2.4 2.3 0.9 1.4 0.8 1.2 0.5 1.1

95% CI 0.2-1.3 0.4-1.7 1.4-3.0 1.5-3.2

0.3-1.3 0.8-2.1 0.4-1.4 0.7-2.0 0.2-0.8

0.4-1.6

VAS for solids

Mean 1.9 1.9 4.3 3.4 2.1 2.0 1.5 2.1 1.1 1.1

95% CI 1.1-2.9 1.2-2.7 3.3-5.2 2.7-4.6

1.2-2.7 1.4-2.8 1.0-2.4 1.3-2.7 0.6-1.6 0.3-1.7

Dakkak score

Mean 8.0 8.4 15.9 12.6 8.3 8.1 6.6 7.1 5.9 6.4

95% CI 5.5-11.6 5.3-11.6 12.4-19.4

9.0-16.3

5.7-10.8

5.7-10.5

3.9-9.2 4.7-9.5 3.5-8.3 3.8-8.9

Data are presented as n (%) or mean with 95% CI. There were no significant differences between the two groups (p≥0.05) LTF (Laparoscopic Toupet fundoplication); LAF (180º Laparoscopic anterior fundoplication); VAS (Visual Analog Scale); Dakkak dysphagia score (0-45)

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At 12 months of follow-up, approximately 90% of all included patients reported control of heartburn.

At 12 months following surgery, 16% of the LTF-group and 17% of the 180˚ LAF-group respectively reported

the presence of dysphagia (p=0.962). The 12 month visual analog score for dysphagia for liquids did not

change in both the LTF- and 180˚ LAF-group compared to the preoperative score (0.8 vs. 0.5, p=0.471, LTF;

1.0 vs. 1.0, p=0.411, 180˚ LAF), nor for solids (2.0 vs. 1.1, p=0.194, LTF; 1.9 vs. 1.0, p=0.107, 180˚ LAF, Table

4). There were no differences between the two-groups at each of the four follow-up periods, with a mean

score of 0.5 and 1.0 for liquids (p=0.313) and a mean score of 1.1 and 1.0 for solids (p=0.535) in the LTF and

180˚ LAF-group respectively at 12 months. The mean Dakkak dysphagia score also did not significantly differ

between the two groups at all four follow-up intervals, with a mean score of 5.9 and 6.4 in the two groups

at 12 months (p=0.773,Table 4). The patient satisfaction score (p=0.679), the Visick score (p=0.934) and

overall outcome (p=0.544) were similar between the two groups at 12 months follow-up, and at the other

three follow-up periods (Table 5).

TABLE 5. SATISFACTION SCORE, VISICK SCORE AND OVERALL OUTCOME



Patient satisfaction

Mean N/A N/A 7.2 7.8 8.0 8.2 8.7 8.3 8.2 8.2

95% CI N/A N/A 6.4-8.0

6.9-8.6

7.2-8.7 7.4-9.0 8.1-9.2

7.5-9.0 7.5-8.9 7.4-9.1

Visick score 1 0.0% 0.0% 9.1% 17.9% 14.6% 28.2% 31.7% 29.7% 29.3% 28.9%

2 7.0% 14.3% 43.2% 46.2% 41.5% 41.0% 39.0% 43.2% 43.9% 47.4%

3 23.3% 9.5% 15.9% 12.% 22.0% 15.4% 17.1% 16.2% 12.2% 7.9%

4 69.8% 76.2% 31.8% 20.5% 22.0% 15.4% 9.8% 10.8% 14.6% 15.8%

5 N/A N/A 0.0% 2.6% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

Overall outcome

Perfect N/A N/A 9.5% 20.5% 17.5% 22.0% 32.6% 28.9% 24.4% 21.4%

Good N/A N/A 66.7% 48.7% 60.0% 53.7% 51.2% 55.3% 58.5% 59.5%

Fair N/A N/A 16.7% 20.5% 15.0% 17.1% 16.3% 10.5% 17.1% 14.3%

Poor N/A N/A 7.1% 10.3% 7.5% 7.3% 0.0% 5.3% 0.0% 4.8%

Undergo surgery again?

Yes N/A N/A 92.7% 94.9% 92.9% 100% 95.3% 95.0% 90.5% 95.1%

No N/A N/A 7.3% 5.1% 7.1% 0.0% 4.7% 5.0% 9.5% 4.9%

Data are presented as n (%) or mean with 95% CI. There were no statistically significant differences between the two groups (p≥0.05 at all follow-up periods). N/A = not applicable . LTF (laparoscopic Toupet fundoplication); LAF (180º laparoscopic anterior fundoplication)

At 12 months, 91% and 95% of the patients in both groups reported that they would undergo surgery again

(p=0.676). Compared to the preoperative usage, the use of acid suppressing drugs, decreased in both

groups at 12 months follow-up (94% to 20%, LTF; 91% to 21%, 180˚ LAF), with no significant difference

in medication usage between the two groups at 12 months (P=0.950). Per-protocol-analysis based on the

type of procedure patients had undergone at the time of completing follow-up, including the two cross-over

patients in whom the LTF was converted to 180˚ LAF, did not influence the results of this trial, apart from the

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Chapter 2

fact that the higher rate of flatulence at one month (P=0.078) and chest pain at six months (P= 0.120) in the

LTF-group compared to 180˚ LAF-group were no longer significant.

UPPER GASTROINTESTINAL ENDOSCOPY

Preoperative upper gastrointestinal endoscopy was performed in 95% of all included patients (Table 6).

Preoperatively, reflux oesophagitis was present in 27 patients (29%), with no differences between the two

groups. Nineteen patients (20%) suffered from Barrett’s oesophagus. Out of the group of 7 patients who did

not have pH studies, endoscopy was used to verify reflux disease. In this group there were no patients with

grade A, 3 with grade B, 1 with grade C and 0 with grade D oesophagitis. Another 3 patients demonstrated

Barrett oesophagus. Three months following surgery, endoscopy was performed in 64 patients (68%). Of

these patients, nine (14%) showed signs of oesophagitis and in 14 patients (22%) Barrett’s oesophagus was

found, with no differences between the two groups (P=1.000 and P=1.000 respectively; Table 6).

Per-protocol-analysis did not change these results.

TABLE 6. PRE- AND POSTOPERATIVE OUTCOME OF OBJECTIVE STUDIES

Preop 6 months postop

LTF LAF LTF LAF

ENDOSCOPY

Studied, n (%) 45 (95.7%) 45 (95.7%) 32 (68.1%) 32 (68.1%)

Oesophagitis Grade A 3 (6.7%) 5 (11.1%) 3 (9.4%) 3 (9.4%)

Grade B 5 (11.1%) 7 (15.6%) 1 (3.1%) 1 (3.1%)

Grade C 2 (4.4%) 3 (6.7%) 0 (0.0%) 1 (3.1%)

Grade D 0 (0.0%) 1 (2.2%) 0 (0.0%) 0 (0.0%)

Barrett’s oesophagus 10 (22.2%) 9 (20.0%) 7 (21.9%) 7 (21.9%)

Hiatal hernia 32 (71.1%) 37 (82.2%) 1 (3.1%) 3 (9.4%)

24-HR PH-STUDY

Studied, n (%) 43 (91.5%) 44 (93.6%) 41 (87.2%) 35 (74.5%)

pH<4 for >4%, n (%) 36 (83.7)* 43 (97.7)* 4 (9.8) 4 (11.4)

Normalisation of acid exposure, n (%) - - 37 (90.2) 31 (88.6)

% acid upright 14.5 (10.2-17.7) 13.7 (11.5-16.0) 2.0 (0.7-3.3) 2.2 (1.1-3.3)

% acid supine 10.4 (4.9-15.8) 14.9 (7.6-22.1) 1.7 (0.3-3.2) 3.5 (0.2-7.6)

% acid total 13.0 (9.7-16.4) 14.1 (10.6-17.5) 1.9 (0.6-3.2) 2.6 (0.8-4.3)

MANOMETRY

Studied, n (%) 27 (57.4%) 28 (59.6%) 28 (59.6%) 23 (48.9%)

LOS resting pressure in kPa 0.8 (0.5-1.1) 0.9 (0.5-1.3) 1.3 (1.0-1.6) 2.1 (1.6-2.6)

LOS residual resting pressure in kPa 0.3 (0.1-0.4) 0.3 (0.1-0.5) 0.3 (0.2-0.5) ^ 1.1 (0.5-1.7) ^

Data are presented as n (%) or mean (95% CI); *p= 0.030; ^ p= 0.008; LTF (laparoscopic Toupet fundoplication); LAF (180º laparoscopic anterior fundoplication)

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OESOPHAGEAL PH-MONITORING AND MANOMETRY

A total of 76 patients (81%) underwent 24-hr oesophageal pH-monitoring three months following surgery.

Postoperative pH<4 more than 4% of the time was found in four patients (10%) within the LTF-group and

four patients (11%) within the 180˚ LAF-group, with a mean percentage time of pH<4 of 1.9% in the LTF-

group versus 2.6% in the 180˚ LAF-group (P=0.483, Table 6). Of these eight patients, one had normal

oesophageal acid exposure pre-operatively. Only one (13%) reported typical reflux symptoms (regurgitation)

at three and six months following surgery and none of these patients reported heartburn. Per-protocol-

analysis did not change these results. Preoperative oesophageal manometry was performed in 55 (59%)

of the included patients and did not demonstrate abnormalities or significant differences between the two

groups (Table 6). Three months following surgery, 51 patients (54%) underwent oesophageal manometry

again, only revealing a significant lower mean residual resting pressure in the LTF-group compared to the

LAF-group (P=0.005;Table 6). Per-protocol-analysis did not change these results.

DISCUSSIONMeta-analyses have demonstrated that LTF and 180˚ LAF provide less side effects and similar reflux control

compared to LNF.6,10 LTF and 180˚ LAF have not been compared in a head-to-head fashion in an adequately

powered RCT. Furthermore, the SAGES guideline for treatment of GORD concluded that there is a paucity

on data and controlled studies with long-term follow-up.36 In a recent comment on a systematic review and

meta-analysis of laparoscopic anterior versus posterior fundoplication37, the need for a well-constructed trial

directly comparing LTF with 180° LAF was again mentioned. The present trial is the only adequately powered

trial comparing laparoscopic partial fundoplications and did not demonstrate any major differences between

LTF and 180˚ LAF during the first 12 months following surgery.

The Dakkak dysphagia score was the primary outcome of this trial and no differences between the two

groups were identified at one-, three, six and 12 months of follow-up. There were no differences in secondary

outcomes like reflux control, overall outcome and patient satisfaction. The only differences that were

observed included a higher prevalence of flatulence one month after LTF and chest pain six months after LTF.

At 12 months these differences were no longer present. The presence of typical post-fundoplication

symptoms also did not significantly differ between the two groups.

In 2015, Daud et al. published the results of a RCT comparing LTF with 180˚ LAF, and found no significant

differences in terms of dysphagia, but a trade-off between reflux versus inability to belch and nausea.26

Heartburn scores were higher after 180˚ LAF accompanied with a trend towards higher pH scores.

Satisfaction after both procedures was similarly high.26 The current study randomized twice as many patients

and the results are in line with the findings of Daud et al, with no major differences in reflux control and

postfundoplication-symptoms between LTF and 180˚ LAF.

Another trial has addressed the differences between open Toupet and anterior fundoplication.38 The anterior

fundoplication was performed in a different way compared to the 180˚ LAF in the current study, with a wrap

circumference of only 120 degrees. This is an important difference since the long-term results of RCTs have

demonstrated that 180˚ LAF offers better reflux control compared to an anterior wrap with a 90 degree

34

Chapter 2

circumference.35 The long-term results of the trial that compared open Toupet and 120˚ anterior

fundoplication demonstrated better reflux control after LTF with less postfundoplication symptoms after

LAF, and similar patient satisfaction in both groups.38

A possible advantage of 180˚ LAF over LTF could be the fact that 180˚ LAF requires less division of short

gastric vessels compared to LTF. However, we did not find a significant difference in total procedure time

between LTF and 180˚ LAF, indicating equal technical feasibility of both procedures. Manometric studies at

three months after surgery demonstrated a significantly lower LOS residual resting pressure in the LTF-group

compared to the 180˚ LAF-group. A possible explanation for this finding could be the fact that significantly

more patients in the LTF-group underwent cruroplasty using both posterior and anterior non-absorbable

sutures. We hypothesized that by using both posterior and anterior sutures, the oesophagus passes the hiatus

in a more horizontal position, with less angulation near the LOS, and a subsequent lower LOS residual resting

pressure compared to patients in whom only posterior sutures were used for cruroplasty. The manometric

studies are in line with the trial of Daud et al, reporting a trend to a lower LOS resting- and residual pressure

after LTF compared to 180˚ LAF.26 These manometric results are in contrast with the Swedish trial in which a

trend toward a higher LOS resting- and residual pressure after LTF was found compared to LAF.39 A possible

explanation for these conflicting results may be the fact that the latter trial used an 120˚ anterior

fundoplication technique that might be inferior to the 180˚ LAF approach used in Daud et al and current

trial.26 This might have resulted in different LOS resting- and residual pressures postoperatively.39 Despite

a significantly lower LOS residual resting pressure in the LTF-group compared to the 180˚ LAF-group, no

difference was found in oesophageal acid exposure during 24-hr oesophageal pH-monitoring, indicating that

the decrease in LOS residual resting pressure did not cause an increase in acidic reflux episodes. Continuing

follow-up, including the oesophageal function tests, will determine whether this finding has any long-term

clinical implications. LOS length was not adequately registered in manometric studies. Therefore we cannot

investigate whenever lower LOS-pressure in the LTF arm is due to a shortening of LOS length.

A possible weakness of our study is the fact that not all of the included patients underwent their post-

operative oesophageal 24-hr pH-study, which is considered the gold standard for diagnosing GORD. It

remains difficult to convince patients of the necessity of invasive postoperative oesophageal function tests

if they experience no postoperative symptoms. This is a common problem in prospective studies describing

outcome of anti-reflux surgery. We did, however, obtain postoperative 24-hr oesophageal pH-studies for

approximately 81% of the patients, demonstrating no significant differences between the two groups and

demonstrating pH<4 for >4% of total time in 10% of the patients after LTF and 11% after 180˚ LAF, of whom

only one patient reported regurgitation and none reported heartburn. A study by our group that compared

the results of laparoscopic Nissen and 180˚ LAF has demonstrated that there are no differences in outcome

between patient who only had subjective outcome assessment and those who completed subjective and

objective follow-up.40 Furthermore, there were no significant difference in symptomatic outcome between

the LTF- and the 180˚ LAF-group, making it unlikely that a higher rate of patients undergoing a post-

operative pH-study would cause a significant difference in recurrent pathological acid exposure between the

two groups.

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2

Investigator bias is deemed unlikely since both surgeons conducted the operations in a similar fashion after

both procedures were trained together and performed surgery on patients together, as well as discussing

intra-operative videos of both techniques before the trial commenced. There was no learning curve as both

surgeons are highly trained in reflux- and upper gastrointestinal surgery.41 In addition, multicenter design and

intention to treat analysis is likely the best reflection of clinical practice.

In the present study, only increased flatulence and chest pain were found to more frequently occur following

LTF compared to 180˚ LAF at one and six months following surgery respectively. There were no differences in

typical reflux symptoms like heartburn and regurgitation and oesophageal acid exposure. Based on

objectified oesophageal studies three months postoperatively, only LOS residual resting pressure was found

to be lower compared to 180˚ LAF. These findings were not reported in other comparable trials.26,38

Unfortunately, two patients who underwent LTF required revision surgery due to acute dysphagia on day five

and 14 postoperative. Both fundoplications were converted to 180˚ LAF with good clinical results. A possible

explanation for these two revisions could be difficulty in creating a “floppy” posterior wrap. However, analysis

of the intraoperative video-material of both primary procedures by EJH and VBN did not demonstrate any

technical errors. Per protocol analysis however, demonstrated that these crossover patients did not influence

the results of this trial.

The effectiveness on patient’s wellbeing of both procedures is demonstrated by high patient satisfaction

and Visick scores. These findings are in line with other trials.26,38 At least 95% of all includes patients would

undergo surgery again under similar conditions. Furthermore, approximately 93% of all patients reported

control of heartburn and a significant reduction in mean heartburn-scores was seen after 12 months, demon-

strating the excellent reflux controlling potential of both procedures.

This trial demonstrates that both LTF and 180˚ LAF are safe and effective in controlling GORD symptoms

and oesophageal acid exposure, with comparably low postoperative side-effects in the short-term and high

patient satisfaction rates. Based on the short-term results of this trial, authors suggest that selecting a LTF or

180˚ LAF should be based on local experience and expertise.

In conclusion, the results of this trial demonstrate equality of LTF and 180˚ LAF as surgical procedures for

GORD, with similar subjective and objective reflux control, post-fundoplication symptoms and patient sat-

isfaction. The long-term results of this RCT need to be awaited to evaluate whether differences develop with

extension of follow-up beyond 12 months.

36

Chapter 2

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28. Toupet A. [Technic of esophago-gastroplasty with phrenogastropexy used in radical treatment of hiatal hernias as a supplement to Heller’s operation in cardiospasms]. Mem Acad Chir (Paris) 1963; 89:384-389.29. Watson A, Jenkinson LR, Ball CS et al. A more physiological alternative to total fundoplication for the surgical correction of resistant gastro-oesophageal reflux. Br J Surg 1991; 78:1088-1094.30. Lundell LR, Dent J, Bennett JR et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut 1999; 45:172-180.31. Johnsson F, Holloway RH, Ireland AC et al. Effect of fundoplication on transient lower oesophageal sphincter relaxation and gas reflux. Br J Surg 1997; 84:686-689.32. Gatenby PA, Bright T, Watson DI. Anterior 180 degrees partial fundoplication--how I do it. J Gastrointest Surg 2012; 16:2297-2303.33. Dakkak M, Bennett JR. A new dysphagia score with objective validation. J Clin Gastroenterol 1992; 14:99-100. 34. Rijnhart-de Jong HG, Draaisma WA, Smout AJ et al. The Visick score: a good measure for the overall effect of antireflux surgery? Scand J Gastroenterol 2008; 43:787-793.35. Broeders JA, Roks DJ, Jamieson GG et al. Five-year outcome after laparoscopic anterior partial versus Nissen fundoplication: four randomized trials. Ann Surg 2012; 255(4):637-42.36. Stefanidis D, Hope WW, Kohn GP et al. Guidelines for surgical treatment of gastroesophageal reflux disease. Surg Endosc 2010; 24:2647-2669.37. Thompson SK, Watson DI. What is the best anti-reflux operation? All fundoplications are not created equal. World J Surg 2015; 39:997-999.38. Engström C, Lönroth H, Mardani J et al. An anterior or posterior approach to partial fundoplication? Long-term results of a randomized trial. World J Surg 2007; 31:1221-1225.39. Engström C, Ruth M, Lönroth H et al. Manometric characteristics of the gastroesophageal junction after anterior versus posterior partial fundoplication. Dis Esophagus 2005; 18:31-36.40. Broeders JA, Broeders EA, Watson DI et al. Objective outcomes 14 years after laparoscopic anterior 180-degree partial versus nissen fundoplication: results from a randomized trial. Ann Surg 2013; 258:233-239.41. Broeders JA, Draaisma WA, Rijnhart-de Jong HG et al. Impact of surgeon experience on 5-year outcome of laparoscopic Nissen fundoplication. Arch Surg 2011; 146:340-346.

3Equal patient satisfaction, quality of life and objective recurrence rate after laparoscopic hiatal hernia repair with and without mesh

J.H. Koetje J.E. OorD.J. RoksH.L. van WestreenenE.J. Hazebroek V.B. Nieuwenhuijs

Accepted in Surgical Endoscopy

Oral presentation at NVGE autumn congress 2016, Veldhoven

40

Chapter 3

ABSTRACT

INTRODUCTION Laparoscopic hiatal hernia repair has become standard practice for most surgeons

performing antireflux surgery. Hiatal hernia repair consists of cruraplasty with

sutures only, or additional reinforcement using mesh. Use of mesh was initiated to

reduce recurrence rates. Recent analyses showed that use of mesh may influence

radiologic recurrence rates, but it does not seem to prevent symptomatic

recurrences and the need for reoperation. This study compares a cohort of patients

regarding clinical and radiological outcomes of primary cruraplasty and cruraplasty with

non-absorbable mesh after laparoscopic hiatal hernia repair.

METHODS Retrospective analysis of prospective followed patients after laparoscopic correction of

hiatal hernia type II-IV in two tertiary referral centers. Radiologic recurrence, symptom

atic recurrence, reoperation rate, complications and patient reported outcome

measures were analyzed for all patients.

RESULTS 189 patients were analysed after laparoscopic hiatal hernia correction with an additional

fundoplication (127 (67.2%) primary correction, 62 (32.8%) with mesh reinforcement).

After a mean follow-up of 39.3 months the overall radiologic recurrence rate was

24.3% and equal in both groups (25.8% (mesh) versus 23.6% (no mesh) P=0.331).

Symptomatic recurrence rate was 13.2% (16.1% versus 11.8%, p=0.495) and reoperation

rate 7.4% (9.7% versus 6.3%), which was comparable between groups. Complications

were equal and no serious mesh-related complications were seen. Health-related

quality of life improved after surgery, dysphagia decreased and patient satisfaction was

high for both groups without significant differences.

CONCLUSION Radiologic recurrence, symptomatic recurrence, and reoperation rate are equal with or

without non-absorbable mesh reinforcement after laparoscopic hiatal hernia repair,

irrespective of hernia size and type. Quality of life, dysphagia and patient satisfaction

was comparable. No serious mesh-related complications occurred. The results of this

study do not support routine use of mesh in hiatal hernia.

41

Equal patient satisfaction, QoL and objective recurrence rate after lap. hiatal hernia repair with and without mesh

3

INTRODUCTIONLaparoscopic repair of large hiatal hernia has become standard therapy for patients with symptomatic hiatal

hernia, and covered around 50% of laparoscopic antireflux procedures in the last decade.1 Hiatal hernia is

associated with impaired quality of life, caused by symptoms including dysphagia, chest pain, reflux,

regurgitation and airway symptoms like cough and dyspnea. It is more common in the elderly patient with a

higher incidence with increasing age.2,3 Surgery consists of dissection of the hernial sac from the mediastinum

into the abdomen, followed by cruraplasty with sutures and fundoplication.4 This procedure has

demonstrated acceptable morbidity and low symptomatic recurrence rate.5-7 More recent studies providing

radiologic follow-up with barium-swallow X-rays, reported high numbers of radiologic, asymptomatic

recurrence hiatal hernia, with rates up to 30-42%.8,9 Although only 5% of these patients had symptomatic

recurrence. An asymptomatic recurrence can become symptomatic over time and can lead to severe c

omplications like strangulation.9,10 In attempt to reduce recurrence rates, several surgeons were looking for

firmer crural repair using mesh. It showed promising results in the first clinical trials.11-15 The use of mesh was

associated with certain rare, but serious complications such as stenosis and erosion that could result in

partial or total gastrectomy or even oesophagectomy.16-19 For that reason, several randomised clinical trials

have compared primary suturing versus prosthetic, non-absorbable and absorbable mesh, not just for

comparing recurrence rates, but to analyse the incidence of mesh-related complications as well.12-14,20 Two

recent meta-analyses demonstrated that all procedures provide comparable results, with a possible favorable

outcome for use of mesh in asymptomatic recurrence rate, but not for reoperation rate.21,22 Patient

satisfaction and quality of life was equal after primary cruraplasty, use of biologic absorbable mesh, and

prosthetic non-absorbable mesh in a recent randomised controlled trial.23

This study describes the symptomatic and objective results of a large cohort of patients that underwent

laparoscopic repair for a symptomatic type II-IV hiatal hernia. Data were prospective collected and retro-

spective analysed. In contrast to many studies we used patient reported outcome measures (PROM’s), to

evaluate patient satisfaction and quality of life after surgery. We hypothesised that clinical outcome between

primary cruraplasty and cruraplasty reinforced with a non-absorbable mesh would be equal. Therefore, the

aim was to analyse radiologic and symptomatic recurrence, and compare reoperations, complications, and

PROM’s to find which factors could be associated with symptomatic recurrence and reoperation.

MATERIALS AND METHODSPATIENT SELECTION

Patients that underwent laparoscopic hiatal hernia repair of a type II, III or IV hiatal hernia with a minimal

follow-up of six months were included in this study. All patients were operated in two tertiary referral centers

for antireflux surgery (both centers >80 cases per year). Patients that were mentally incapable, younger than

18 years old at time of surgery, incapable to speak the Dutch language or patients that were diagnosed with

a different disease during preoperative investigations or during surgery were excluded. Also, patients with

previous antireflux surgery were excluded.

42

Chapter 3

PREOPERATIVE WORKUP

The majority of patients were referred by the gastroenterologist. Preoperative upper gastrointestinal

endoscopy, barium-swallow X-ray, and/or computed tomography (CT) were performed preoperative to

confirm the diagnosis of hiatal hernia. Oesophageal manometry and 24-hours-pH-metric were only

performed on clinical indication. Hiatal hernia was categorised according to the Guidelines for the

management of hiatal hernia by the Society of American Gastrointestinal and Endoscopic Surgeons.24

DATA COLLECTION

Collection of data using questionnaires was prospective. Completion of data was done retrospective using

electronic patient files. Comorbidity was categorised as presence of cardiovascular disease (including

hypertension, cardiac arrhythmias, coronary artery disease, peripheral vascular disease, cerebrovascular

disease); presence of diabetes mellitus (including type I and II); presence of Chronic Obstructive Pulmonary

Disease (COPD); and a history of previous abdominal surgery (either laparoscopic or open surgery). Primary

symptoms were categorised into dysphagia, airway symptoms (coughing and dyspnea), reflux, chest pain and

anaemia.

SURGICAL TECHNIQUE

All procedures were performed laparoscopic, no conversions to laparotomy were needed. First step in the

procedure was reduction of the stomach, and if present other abdominal organs, followed by dissection

of the hernia sac. When exposure of the hiatus was gained and the oesophagus was sufficiently mobilised,

posterior cural repair, and anterior repair when deemed necessary, was performed using non-absorbable

sutures. When there was too insufficient or weak crural tissue, a U-shaped, non-absorbable mesh was used

for posterior crural reinforcement (TiMESH®, pfm medical titanium gmbh, Nürnberg, Germany). This was

fixed using non-absorbable sutures or absorbable tackers, while carefully avoiding direct contact to the

oesophagus. In addition a fundoplication was performed to avoid recurrent reflux. According to the

preference of the surgeon this was either a 180° anterior partial fundoplication (180°LAF),25,26 a 270°

posterior partial Toupet fundoplication (LTF)27 or a 360° total Nissen fundoplication (LNF).28

FOLLOW-UP

Barium-swallow X-rays were performed three to six months postoperative. Postoperative endoscopy, CT,

24-hours-pH-metric, and/or oesophageal manometry were performed only on indication given the invasive

character of these investigations. One hospital prospectively followed patients using validated

questionnaires, including the validated Gastro-Esophageal Reflux Disease health related Quality of Life

(GERD-hr-QoL) for GERD-related quality of life,29-32 and the validated QLQ-OES-24 for scoring

dysphagia.33,34 Furthermore, symptoms were scored on a 10-point Visual Analogue Scales,35 and assessed

their satisfaction about preoperative information, quality of care (outpatient, surgical department, ward, etc),

waiting time for the operation, and postoperative care on 10-point Visual Analogue Scales were assessed.

Finally, patients were asked in retrospect if they would undergo the same operation again, should have

undergone this operation earlier and if they would recommend this operation to a close relative or good

friend with equal symptoms, knowing what the results are after surgery. Patients were asked to complete

43


3

these questionnaires preoperatively, and at three months postoperative, one year postoperative and then

yearly up until five years postoperative. Data collection was either on paper or online.

STATISTICS

Parametrically distributed data were analysed using Student t tests. Non-parametric data were analysed using

Mann-Whitney U tests. Categorical data were analysed using Fisher´s exact tests or Chi-square tests.

Univariate logistic regression analyses were performed to predict risk factors. Multivariate logistic regressions

were performed with factors that showed significant univariate regression (P<0.05). Statistical analyses were

performed using IBM´s Statistical Package for Social Sciences (SPSS), version 22 for Apple Macintosh OS

(IBM corp., Armonk, New York, USA). A p value of less than 0.05 was considered to be statistically

significant.

ETHICAL APPROVAL

Patients gave informed consent and were informed about the purposes of the completed questionnaires and

securely saved data. The Institutional Review Board of the hospitals has evaluated our study protocol and

approved it without further obligations.

RESULTSPATIENT CHARACTERISTICS

Between July 2009 and December 2015, a total of 189 patients with a mean age of 66.0 ± 11.2 years

underwent laparoscopic hiatal hernia repair with additional fundoplication. Mean follow-up was 39.3

months ± 17.2. Patients were equally distributed over both hospitals (109 patients (57.7%) in hospital 1 versus

80 patients (42.3%) in hospital 2). 145 patients (76.7%) were female, 44 were male (23.3%), and mean

body mass index (BMI) was 28.8 ± 4.3. Age, gender, and BMI did not differ between the two groups. The

proportion of ASA II patients was higher in the non-mesh group and a higher percentage of ASA I and

III in the mesh group (P=0.038). Presence of cardiovascular disease was higher in the non-mesh group

(P=0.008). Indications for surgery for the overall group were dysphagia in 29.3% of patients, chest pain in

28.3%, reflux and regurgitation complaints in 20.1%, airway complaints like dyspnea or coughing in 17.4%,

and anaemia or bleeding in 4.9% of patients. These indications for surgery were equal in the non-mesh and

the mesh group. Hiatal hernia type and percentage of the stomach in the thoracic cavity was equal for both

groups. The majority of patients had a type III hiatal hernia (67.2%) and more than 50% of the stomach

displaced (77.1%). A non-absorbable mesh was used in 62 patients (32.8%). Baseline characteristics are

described in table 1.

PERIOPERATIVE OUTCOME

Table 2 demonstrates perioperative outcome. The majority of patients received a 180° anterior

fundoplication (67.9%), which was most frequently conducted in the non-mesh group (89.7% versus

23.0%). A Toupet fundoplication was performed in 30.5% of patients and more common in the mesh group

(77.0% versus 7.9% in the non-mesh group; P<0.001). Laparoscopic Nissen fundoplication was performed

in three cases of severe Barrett’s oesophagus (2.4%). Intra-operative complications occurred in 9.8% of

44

Chapter 3

TABLE 1. PATIENT CHARACTERISTICS

Mesh (n=62)

No Mesh (n=127)

P-value

Agea 64.1 ±12.8 66.9 ±10.3 0.140

Genderb Male 15 (24.2%) 29 (22.8%) 0.856

Female 47 (75.8%) 98 (77.2%)

BMIa 28.9 ± 4.7 28.7 ± 4.2 0.873

ASAa I 9 (14.5%) 10 (7.9%) 0.038

II 38 (61.3%) 100 (78.7%)

III 15 (24.2%) 17 (13.4%)

Comorbidityb Cardiovascular 21 (33.9%) 70 (55.1%) 0.008

Diabetes Mellitus 4 (6.5%) 10 (7.9%) 1.000

Abdominal surgery 27 (43.5%) 65 (51.6%) 0.353

COPD 10 (16.1%) 19 (15.0%) 0.832

Primary symptomb

Dysphagia 16 (27.1%) 38 (30.4%) 0.929

Airway 12 (20.3%) 20 (16.0%)

Reflux 12 (20.3%) 25 (20.0%)

Chest pain 17 (28.8%) 35 (28.0%)

Anemia 2 (3.4%) 7 (5.6%)

Hernia typeb II 6 (9.7%) 13 (10.2%) 0.483

III 45 (72.6%) 82 (64.6%)

IV 11 (17.7%) 32 (25.2%)

Percentage intra-thoracic stomachb

0-24% 1 (1.6%) 7 (5.6%) 0.113

25-74% 26 (42.6%) 68 (72.3%)

75-100% 34 (55.7%) 51 (40.5%)

BMI = Body Mass Index; ASA = American Society of Anesthesiologists physical status score; COPD = Chronic Obstructive Pulmonary Disease; Data presented as either a:mean ± standard deviation, or b:number (percentage).

operations, without any major complications and were equal in both groups. Minor intra-operative compli-

cations consisted of asymptomatic pleural tear (3.2%, n=6); bleeding (1.6%, n=3); atrial fibrillation de novo

(1.6%, n=3); small lesion of the spleen (1.1%, n=2); perforation of the oesophagus (0.5%; n=1); gastric

perforation (0.5%; n=1). Complications were recognised and repaired if necessary. Median hospital stay was

two days (IQR 2.0), and median duration of surgery was 100 minutes (IQR 42.5). Operation times were

longer in the mesh-group (110 minutes versus 95 minutes; P=0.045). Postoperative complications were

present in 11.6% of patients (n=22) and were equal in both groups. Postoperative complications consisted of

urinary tract infection (2.6%; n= 5); pneumonia (1.6%; n=3); asymptomatic atelectasis (1.1%; n=2);

pulmonary oedema (1.1%; n=2); dysphagia requiring reoperation in one case (1.1%; n=2); mediastinal bleeding

requiring reoperation (0.5%; n=1); distal oesophageal stenosis requiring oesophageal stenting (0.5%; n=1);

45


3

recurrent hiatal hernia causing pain requiring reoperation (0.5%; n=1); and five other rare complications (e.g.

pulmonary embolus, gastro-enteritis, oesophageal oedema, atrial fibrillation de novo, and constipation).

There were no mesh-related complications during short- or long-term follow-up. Duration of follow-up was

different between the two groups.

TABLE 2: PERIOPERATIVE CHARACTERISTICS AND OUTCOME

Mesh (n=62) No Mesh (n=127) P-value

Fundoplication typea 180°LAF 14 (23.0%) 113 (89.7%) <0.001

LTF 47 (77.0%) 10 (7.9%)

LNF 0 3 (2.4%)

Minor intra-operative complicationsa 5.0 (8.1%) 12 (9.4%) 1.000

Time of surgeryb 110 (30) 95 (50) 0.045

Hospital daysb 2.0 (2.0) 2.0 (2.0) 0.273

Postoperative complicationsa 8 (12.9%) 14 (11.0%) 0.810

Radiologic recurrencea 16 (25.8%) 30 (23.6%) 0.331

Symptomatic recurrencea 10 (16.1%) 15 (11.8%) 0.495

Reoperationa 6 (9.7%) 8 (6.3%) 0.393

Satisfaction after surgery (n=88)b 8.5 (3.0) 9.0 (2.0) 0.946

Follow-up after surger (months)c 49.2 (16.2) 34.5 (15.6) <0.001

180°LAF = 180° anterior fundoplicationLTF = Toupet (270° posterior) fundoplicionLNF = Nissen (360°) fundoplication Data presented as either a: number (percentage), b: median (interquartile range), or c: mean (SD).

SYMPTOMATIC AND OBJECTIVE OUTCOME

109 patients were invited for follow-up using PROM’s (57.7%). Response rate was 80.7% (n=88) and mean

follow-up was 33.3 months ± 13.6. Median satisfaction of surgery was 9.0 (IQR 2.0) and equal in both

groups. GERD-hr-QoL improved significant postoperatively (P<0.001, n=77) from median 7.0 (IQR 15.0)

preoperative, to 2.0 (IQR 2.0) postoperative. This improvement was equal for primary cruraplasty and use of

mesh (figure 1). The QLQ-OES-24 also showed significant improvement after surgery (P<0.001, n=74) from

49 (IQR 15.0) to 34 (IQR 12.0). No differences were seen between the groups with crural repair with sutures

only and the group with crural reinforcement using mesh (figure 2).Radiologic recurrence was investigated

in 153 patients (81.0%). Radiologic recurrence was present in 46 patients (24.3%) and was equal for both

groups (25.8%, n=16 in mesh versus 23.6%, n=30 in sutures; P=0.749). Symptomatic recurrence rate was

13.2% and equal in both groups as well (P=1.000). Reoperation rate was 7.4% (n=14) and comparable in the

group with and without mesh. 13 reoperations were late (after > 4 weeks), mean time between primary op-

eration and reoperation was 19.4 months ± 13.8, this was equal in the mesh- and sutures-group (P=0.902).

Only one reoperation was done early (after five days). This was for acute recurrence of hiatal hernia with

obstruction.

46

Chapter 3

0

1

2

3

4

5

6

7

8

9Primary cruroplasty

Mesh

T3T2T1Preoperative

FIGURE 1. GERD-HR-QOL BEFORE AND AFTER LAPAROSCOPIC HIATAL HERNIA REPAIRT1 = three months postoperative (n=69); T2 = 12 months postoperative (n=55); T3 = 24 months postoperative (n=32)GERD-hr-QoL = Gastroesophageal Reflux Disease health-related quality of life questionnaire. All postoperative scores show significant improvement compared to preoperative (P<0.001; preop vs T2 P=0.001). No difference in postoperative scores. No difference between mesh and primary cruroplasty.

0

5

10

15

20

25

30

35

40

45

50Primary cruroplasty

Mesh

T3T2T1Preoperative

FIGURE 2. QLQ-OES24 SCORES BEFORE AND AFTER LAPAROSCOPIC HIATAL HERNIA REPAIRT1 = three months postoperative (n=69); T2 = 12 months postoperative (n=55); T3 = 24 months postoperative (n=32).QLQ-OES24 = Quality of Life questionnaire scoring dysphagia after surgery. All postoperative scores show significant improvement compared to preoperative (P<0.001). No difference in postoperative scores. No difference between mesh and primary cruroplasty.

RISK FACTOR ANALYSES

Univariate analyses demonstrated that age, BMI and previous abdominal surgery might be predictive factors

for reoperation (table 3). Specific predictive factors for radiologic recurrence and symptomatic recurrence

were not found. Use of mesh is not found to be a risk factor for radiologic recurrence, symptomatic

recurrence or reoperation. Multivariate analyses showed comparable results and did not alter the influence of

these predictive factors.

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3

TABLE 3. UNIVARIATE ANALYSES

Radiologic recurrence Symptomatic recurrence Reoperation

OR (95% CI) P-value OR (95% CI) P-value OR 95% CI P-value

Age 0.985 (0.954-1.017) 0.348 0.971 (0.936-1.007) 0.108 0.954 (0.912-0.998) 0.042

Sex 0.734 (0.334-1.611) 0.441 0.586 (0.233-1.469) 0.254 0.370 (0.121-1.131) 0.081

BMI 0.923 (0.848-1.005 0.065 0.942 (0.850-1.044) 0.256 0.869 (0.756-0.999) 0.049

ASA 1.106 (0.525-2.329 0.791 1.276 (0.563-2.894) 0.559 0.754 (0.260-2.186) 0.603

Cardiovascular comorbidity

1.019 (0.510-2.034) 0.958 1.440 (0.617-3.362) 0.399 0.794 (0.265-2.384) 0.681

Abdominal surgery history

0.727 (0.363-1.458) 0.369 0.453 (0.185-1.110) 0.083 0.260 (0.070-0.966) 0.044

Hernia type 0.766 (0.408-1.437) 0.406 0.989 (0.465-2.104) 0.977 0.825 (0.310-2.191) 0.699

Percentage intra-thoracic stomach

1.018 (0.778-1.331) 0.898 0.851 (0.610-1.186) 0.341 0.810 (0.526-1.247) 0.338

Fundo 1.637 (0.824-3.251) 0.159 1.291 (0.582-2.862) 0.529 1.433 (0.525-3.911) 0.483

Intra-operative complications

1.064 (0.348-3.257) 0.913 2.183 (0.651-7.323) 0.206 3.136 (0.782-12.573) 0.107

Mesh 1.505 (0.715-3.167) 0.282 1.410 (0.594-3.351) 0.436 1.594 (0.528-4.812) 0.408

Postoperative complications

0.542 (0.171-1.719) 0.298 1.026 (0.280-3.757) 0.969 1.292 (0.269-6.194) 0.749

BMI = Body Mass Index; ASA = American Society of Anesthesiologists physical status score; OR = Odds ratio; CI = confidence interval.

LARGE HIATAL HERNIAS

Table 4 shows a subanalysis of 85 patients suffering of a large hiatal hernia, categorised as more than 75% of

intrathoracic stomach. Intra-operative and postoperative complication rates were comparable with the overall

group, with no differences in complication rate between reinforcement with mesh and primary cruraplasty.

Radiologic recurrence, symptomatic recurrence and reoperation rates were all equal in both groups,

comparable with the analyses in the complete cohort.

TABLE 4. SUBANALYSIS FOR LARGE HIATHAL HERNIA (>75% INTRATHORACIC STOMACH);

PERIOPERATIVE CHARACTERISTICS AND OUTCOME

Mesh (n=34) No Mesh (n=51) P-value

Minor intra-operative complicationsa 3 (8.8%) 5 (9.8%) 1.000

Time of surgeryb 120 (43.3) 104 (45) 0.232

Hospital daysb 2.0 (2.8) 2.0 (2.0) 0.949

Postoperative complicationsa 5 (14.7%) 5 (9.8%) 0.512

Radiologic recurrencea 8 (23.5%) 13 (25.4%) 0.749

Symptomatic recurrencea 4 (11.8%) 5 (9.8%) 1.000

Reoperationa 2 (5.9%) 4 (7.8%) 1.000

Data presented as either a:mean ± standard deviation, or b:number (percentage).

48

Chapter 3

DISCUSSIONThis study describes the results of a large cohort of patients suffering from a symptomatic hiatal hernia. After

laparoscopic correction of these large hiatal hernias, radiologic recurrence rate was 24.3%, symptomatic

recurrence rate was 13.2%, but only 7.4% of patients needed reoperation due to hiatal hernia recurrence.

This was equal for primary cruraplasty and for cruraplasty with the use of prosthetic mesh. Univariate and

multivariate analyses could not reveal a reduction of a symptomatic recurrence or reoperation rate with use of

mesh. Age, previous abdominal surgery and body mass index were associated with higher symptomatic

recurrence and reoperation. This is explained by difficulties during surgery in patients after previous

abdominal surgery, higher BMI that is associated with higher complication rates after surgery, and weakening

of muscular and fascia tissue with increasing age. However, a recent study demonstrated laparoscopic

correction of large hiatal hernias to be safe in the elderly patient, when carefully selected.36 Minor

perioperative (9.8%) and postoperative complications (11.2%) were comparable in both groups and no major

mesh-related complications occurred, similar with the previously mentioned trials. Only the time of surgery

was significantly different between the groups. Prolonged operation time in the mesh-group was expected,

as the reinforcement with mesh carries an extra step in the procedure. This was also described in the study of

Frantzides et al,12 but not in other studies nor in pooled data in meta-analyses.7,13,21,22

A subanalyis of the large hiatal hernias in this cohort showed comparable results. Except for time of surgery,

which was prolonged for both procedures, but not significantly longer for repair with mesh when compared

to primary cruraplasty. Patient reported satisfaction was high for both groups. Health related quality of life on

both the reflux-scores (GERD-hr-QoL) and the dysphagia-scores showed significant improvement following

surgery. All scores were comparable between primary cruraplasty and reinforcement with mesh.

This study demonstrates no difference in objective en symptomatic recurrence after laparoscopic hiatal

hernia repair with primary cruraplasty versus non-absorbable mesh. This is in contrast to most previously

published trials and meta-analyses. Granderath et al13 and Frantzides et al12 found lower recurrence rate with

use of prosthesis compared to primary cruraplasty. Frantzides even found a 0% recurrence rate using a

“keyhole” polytetrafluorethylene (PTFE) mesh, that surrounded the whole oesophagus. Since no

long-term follow-up was reported, it is unclear whether mesh related complications occurred on later term

or recurrence rates altered in time. Comparable reduction in recurrence rate has not been published yet. Two

meta-analyses described higher recurrence rates after use of sutures only. Antoniou et al. found 24.3%

recurrence following primary cruraplasty after six months, compared to 5.8% after use of mesh.37 Furnee

et al described comparable results with recurrence rate of 26.3% following primary crural correction and

14.6% with use of mesh.38 Oelschlager et al reported promising results after six months using an absorbable

mesh, with 9% recurrence in the mesh-reinforced group and 24% recurrence rate in the primary cruraplasty

group.14 But the five-year results that were published in 2011 revealed different numbers: 54% recurrence in

the group that received a mesh, 59% recurrence in the group after primary correction.15 Reoperation rates

for recurrence were low: only 3.5% in the group after primary cruraplasty. Watson et al published 12 months

results of a three-armed trial using primary correction, absorbable mesh and non-absorbable mesh, showing

comparable results with our study. They found no difference in recurrence, radiologic nor symptomatic.7

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3

Meta-analyses of Memon et al and Tam et al confirmed these findings.21,22

A possible weakness of this study is that the groups are not randomised for the different treatments. It was

the surgeon’s decision to perform primary cruraplasty or reinforce the cruraplasty with mesh. However, we

did analyse both groups and did not find major differences in patient characteristics and perioperative

characteristics. Primary symptoms, hiatal hernia size and percentage of intrathoracic stomach was equal in

both groups. We therefore suggest that the groups are comparable. Another possible weakness might be

the difference in fundoplication type, although it is not known that this could influence recurrence rate after

hiatal hernia correction. In the univariate analyses fundoplication type did not influence recurrence rate.

Duration of follow-up is not equal. Follow-up is shorter in the group without mesh, what can be explained

due to the difference in group size and therefore more recent patients that underwent surgery without mesh.

The majority of studies that describe results after laparoscopic hiatal hernia repair focus on clinical and

objective outcome. However, patient-reported outcome measures (PROM’s) like quality of life and

satisfaction scores are important as a reflection of outcome that is more relevant to the individual patient.39

Few studies describe quality of life using the Short-Form 36.15,23 However, this might not be an adequate

measure for symptom and quality of life alteration after laparoscopic antireflux surgery.32 Health-related

quality of life measures like the GERD-hr-QoL and the Gastrointestinal Quality of Life Index (GIQLI) and

symptom scores using Visual Analog Scores are more reliable for outcome measurement. In our

prospective data collection we use PROM’s to evaluate outcome. This study describes significant

improvement of health-related quality of life and high patient satisfaction, using validated questionnaires.

In conclusion: our study demonstrates comparable recurrence rates, both radiologic (objective) and

symptomatic, after primary cruraplasty and mesh reinforced cruraplasty. Reoperation rate is also equal.

Patient reported outcome measures reflecting patient satisfaction after surgery and quality of life are equal in

both groups as well. The data in this study do not support the routine use of mesh. Randomised clinical trials

comparing mesh and primary crural repair, using health-related quality of life measures and symptom scores,

as well as radiologic versus symptomatic recurrence rates and reoperation rates have been undertaken. Long-

term results of these randomised trials should be awaited before drawing definite conclusions about the use

of mesh in hiatal hernia repair.

50

Chapter 3

REFERENCES 1. Engstrom C, Cai W, Irvine T, et al. Twenty years of experience with laparoscopic antireflux surgery. Br J Surg. 2012;99(10):1415-1421.2. Lal DR, Pellegrini CA, Oelschlager BK. Laparoscopic repair of paraesophageal hernia. Surg Clin North Am. 005;85(1): 105-18, x.3. Grotenhuis BA, Wijnhoven BP, Bessell JR, Watson DI. Laparoscopic antireflux surgery in the elderly. Surg Endosc. 2008;22(8):1807-1812.4. Wijnhoven BP, Watson DI. Laparoscopic repair of a giant hiatus hernia--how I do it. J Gastrointest Surg. 2008;12(8): 1459-1464.5. Edye M, Salky B, Posner A, Fierer A. Sac excision is essential to adequate laparoscopic repair of paraesophageal hernia. Surg Endosc. 1998;12(10):1259-1263.6. Watson DI, Davies N, Devitt PG, Jamieson GG. Importance of dissection of the hernial sac in laparoscopic surgery for large hiatal hernias. Arch Surg. 1999;134(10):1069-1073.7. Watson DI, Thompson SK, Devitt PG, et al. Laparoscopic repair of very large hiatus hernia with sutures versus absorbable mesh versus nonabsorbable mesh: A randomized controlled trial. Ann Surg. 2015;261(2):282-289.8. Hashemi M, Peters JH, DeMeester TR, et al. Laparoscopic repair of large type III hiatal hernia: Objective followup reveals high recurrence rate. J Am Coll Surg. 2000;190(5):553-60; discussion 560-1.9. Aly A, Munt J, Jamieson GG, Ludemann R, Devitt PG, Watson DI. Laparoscopic repair of large hiatal hernias. Br J Surg. 2005;92(5):648-653.10. Stylopoulos N, Gazelle GS, Rattner DW. Paraesophageal hernias: Operation or observation? Ann Surg. 2002;236(4):492-500; discussion 500-1.11. Carlson MA, Richards CG, Frantzides CT. Laparoscopic prosthetic reinforcement of hiatal herniorrhaphy. Dig Surg. 1999;16(5):407-410.12. Frantzides CT, Madan AK, Carlson MA, Stavropoulos GP. A prospective, randomized trial of laparoscopic polytetrafluoro ethylene (PTFE) patch repair vs simple cruroplasty for large hiatal hernia. Arch Surg. 2002;137(6):649-652.13. Granderath FA, Schweiger UM, Kamolz T, Asche KU, Pointner R. Laparoscopic nissen fundoplication with prosthetic hiatal closure reduces postoperative intrathoracic wrap herniation: Preliminary results of a prospective randomized functional and clinical study. Arch Surg. 2005;140(1):40-48.14. Oelschlager BK, Pellegrini CA, Hunter J, et al. Biologic prosthesis reduces recurrence after laparoscopic paraesophageal hernia repair: A multicenter, prospective, randomized trial. Ann Surg. 2006;244(4):481-490.15. Oelschlager BK, Pellegrini CA, Hunter JG, et al. Biologic prosthesis to prevent recurrence after laparoscopic paraesophageal hernia repair: Long-term follow-up from a multicenter, prospective, randomized trial. J Am Coll Surg. 2011;213(4):461-468.16. Tatum RP, Shalhub S, Oelschlager BK, Pellegrini CA. Complications of PTFE mesh at the diaphragmatic hiatus. J Gastrointest Surg. 2008;12(5):953-957.17. Stadlhuber RJ, Sherif AE, Mittal SK, et al. Mesh complications after prosthetic reinforcement of hiatal closure: A 28-case series. Surg Endosc. 2009;23(6):1219-1226.18. Hazebroek EJ, Leibman S, Smith GS. Erosion of a composite PTFE/ePTFE mesh after hiatal hernia repair. Surg Laparosc Endosc Percutan Tech. 2009;19(2):175-177.19. Frantzides CT, Carlson MA, Loizides S, et al. Hiatal hernia repair with mesh: A survey of SAGES members. Surg Endosc. 2010;24(5):1017-1024.20. Watson DI, Thompson SK, Devitt PG, et al. Laparoscopic repair of very large hiatus hernia with sutures versus absorbable mesh versus nonabsorbable mesh: A randomized controlled trial. Ann Surg. 2015;261(2):282-289.21. Memon MA, Memon B, Yunus RM, Khan S. Suture cruroplasty versus prosthetic hiatal herniorrhaphy for large hiatal hernia: A meta-analysis and systematic review of randomized controlled trials. Ann Surg. 2016;263(2):258-266.22. Tam V, Winger DG, Nason KS. A systematic review and meta-analysis of mesh vs suture cruroplasty in laparoscopic large hiatal hernia repair. Am J Surg. 2016;211(1):226-238.23. Koetje JH, Irvine T, Thompson SK, et al. Quality of life following repair of large hiatal hernia is improved but not influenced by use of mesh: Results from a randomized controlled trial. World J Surg. 2015;39(6):1465-1473.24. Kohn GP, Price RR, Demeester SR, et al. Guidelines for the management of hiatal hernia - A SAGES guideline. http://www.sages.org/publications/guidelines/guidelines-for-the-management-of-hiatal-hernia. Updated 2013. Accessed 06/15/2016.25. Watson A, Jenkinson LR, Ball CS, Barlow AP, Norris TL. A more physiological alternative to total fundoplication for the surgical correction of resistant gastro-oesophageal reflux. Br J Surg. 1991;78(9):1088-1094.26. Gatenby PA, Bright T, Watson DI. Anterior 180 degrees partial fundoplication--how I do it. J Gastrointest Surg. 2012;16(12): 2297-2303.

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27. Toupet A. Technic of esophago-gastroplasty with phrenogastropexy used in radical treatment of hiatal hernias as a supplement to heller’s operation in cardiospasms. Mem Acad Chir (Paris). 1963;89:384-389.28. Jamieson GG, Watson DI, Britten-Jones R, Mitchell PC, Anvari M. Laparoscopic nissen fundoplication. Ann Surg. 1994;220(2):137-145.29. Velanovich V, Vallance SR, Gusz JR, Tapia FV, Harkabus MA. Quality of life scale for gastroesophageal reflux disease. J Am Coll Surg.1996;183(3):217-224.30. Mouli VP, Ahuja V. Questionnaire based gastroesophageal reflux disease (GERD) assessment scales. Indian J Gastroenterol. 2011;30(3):108-117.31. Rentz AM, Battista C, Trudeau E, et al. Symptom and health-related quality-of-life measures for use in selected gastrointestinal disease studies: A review and synthesis of the literature. Pharmacoeconomics. 2001;19(4):349-363.32. Koetje JH, Nieuwenhuijs VB, Irvine T, Mayne GC, Watson DI. Measuring outcomes of laparoscopic anti-reflux surgery: Quality of life versus symptom scores? World J Surg. 2016;40(5):1137-1144.33. Blazeby JM, Alderson D, Winstone K, et al. Development of an EORTC questionnaire module to be used in quality of life assessment for patients with oesophageal cancer. the EORTC quality of life study group. Eur J Cancer. 1996;32A(11):1912- 1917.34. Viklund P, Lindblad M, Lagergren J. Influence of surgery-related factors on quality of life after esophageal or cardia cancer resection. World J Surg. 2005;29(7):841-848.35. Grant S, Aitchison T, Henderson E, et al. A comparison of the reproducibility and the sensitivity to change of visual ana logue scales, borg scales, and likert scales in normal subjects during submaximal exercise. Chest. 1999;116(5):1208-1217.36. Oor JE, Koetje JH, Roks DJ, Nieuwenhuijs VB, Hazebroek EJ. Laparoscopic hiatal hernia repair in the elderly patient. World J Surg. 2016;40(6):1404-1411.37. Antoniou SA, Antoniou GA, Koch OO, Pointner R, Granderath FA. Lower recurrence rates after mesh-reinforced versus simple hiatal hernia repair: A meta-analysis of randomized trials. Surg Laparosc Endosc Percutan Tech. 2012;22(6): 498-502.38. Furnee E, Hazebroek E. Mesh in laparoscopic large hiatal hernia repair: A systematic review of the literature. Surg Endosc. 2013;27(11):3998-4008.39. Kamolz T, Granderath F, Pointner R. Laparoscopic antireflux surgery: Disease-related quality of life assessment before and after surgery in GERD patients with and without barrett’s esophagus. Surg Endosc. 2003;17(6):880-885.

4Quality of life following repair of large hiatal hernia is improved but not influenced by use of mesh: results from a randomised controlled clinical trial

J.H. KoetjeT. IrvineS.K. ThompsonP.G. DevittS.D. WoodsA. AlyG.G. JamiesonD.I. Watson

World Journal of Surgery, 2015; 39 (6): 1465-1473

54

Chapter 4

ABSTRACT

INTRODUCTION Laparoscopic surgery is the treatment of choice for repair of large hiatus hernia, but

can be followed by recurrence. Repair with prosthetic mesh has been recommended

to prevent recurrence, although complications following mesh repair have generated

disagreement about whether or not mesh should be used. The early objective and

clinical results of a randomised trial of repair with mesh vs. sutures have been reported,

and revealed few differences. In the current study we evaluated quality of life outcomes

within this trial at follow-up to 2 years.

METHODS In a multicenter prospective double-blind randomised trial three methods for repair of

large hiatus hernia were compared: sutures vs. repair with absorbable mesh (Surgisis)

vs. non-absorbable (Timesh). Quality of life assessment using the Short Form 36

(SF-36) questionnaire was undertaken at 3, 6, 12 and 24 months after surgery.

SF-36 outcomes (8 individual scales and 2 composite scales) were determined for each

group, and compared between groups, and across different follow-up points.

RESULTS 126 patients were enrolled - 43 sutures, 41 absorbable mesh and 42 non-absorbable

mesh. 115 (91.3%) completed a preoperative questionnaire, and 113 (89.7%)

completed the post-operative questionnaire at 3 months, 116 (92.1%) at 6 months, 114

(90.5%) at 12 months, and 91 (72.2%) at 24 months. The SF-36 Physical and Mental

Component scores (PCS and MCS) improved significantly following surgery, and this

improvement was sustained across 24 months follow-up (p<0.001 for PCS and MCS

at each follow-up point). There were no significant differences between the groups for

the component scores or the eight SF-36 subscale scores at each follow-up time. 29

individuals had a recurrence at 6 months follow-up, of which 9 were symptomatic. The

PCS were higher in patients with recurrence versus without (p<0.01), and in patients

with a symptomatic recurrence vs. asymptomatic recurrence versus no recurrence

(p=0.001).

CONCLUSION SF-36 measured quality of life improved significantly after repair of large hiatal hernia

at up to 2 years follow-up, and there were no differences in outcome for the different

repair techniques. The use of mesh vs. no mesh in repair of large hiatal hernia did not

influence quality of life.

55

QoL following repair of large hiatal hernia is improved but not influenced by use of mesh: results from a RCT

4

INTRODUCTION

Laparoscopic approaches are standard for the surgical treatment of gastro-oesophageal reflux disease

(GORD) and hiatus hernia (HH), and achieve good clinical outcomes in most patients.1,2 A subgroup

undergoing surgery present with a very large hiatus hernia and when more than 50% of the stomach

herniates, the stomach can rotate and lead to mechanical symptoms including chest pain, early satiety,

dysphagia, vomiting, and gastric volvulus. A standard approach to laparoscopic repair of very large hiatus

hernias entails complete dissection of the hernia sac from the mediastinum, hiatal repair with posteriorly

placed sutures, followed by construction of a fundoplication.3 Initial clinical outcomes following this

approach are good, but objective follow-up using barium meal X-ray has demonstrated radiological

recurrence rates of 25-45% at late follow-up, although less than 5% of patients actually develop symptoms

from a recurrent hernia.4-6 However, there are concerns that radiological hernia recurrences could become

symptomatic or progress to complications at later follow-up,4-6 and for this reason “tension-free” repair

techniques using prosthetic mesh have been proposed.7 Whilst uncontrolled studies suggest mesh

reinforcement might be followed by lower recurrence rates,7-9 the use of mesh can also be followed by

significant complications such as erosion of mesh into the oesophageal or gastric lumen, and surgery to deal

with this can lead to oesophagectomy.10,11 Absorbable biomeshes are advocated by some surgeons for hiatal

hernia repair to avoid mesh erosion.12 To date, only a few randomised controlled trials have compared mesh

vs. sutures for repair of large hiatal hernias. Frantzides et al and Oeschlager et al both reported reductions in

hernia recurrence at short term follow-up,12,13 although at later follow-up Oeschlager et al identified no

differences.14 We recently reported the outcomes for a trial which randomised 126 patients to repair with

sutures vs. absorbable vs. non-absorbable mesh, and showed no differences in hernia recurrence rates at 12

months follow-up for patients undergoing sutured vs. mesh repair.15 All previous papers reporting outcomes

from randomised trials have focused on objective investigations and hernia recurrence rates.

There can, however, be differences between objectively assessed surgical outcomes and patient reported

outcomes. It is also known that quality of life is impaired in patients suffering gastro-oesophageal reflux,16-18

and improves following laparoscopic antireflux surgery.19,20 In our randomised trial of large hiatus hernia repair

with sutures vs. absorbable mesh vs. non-absorbable mesh, we also measured quality of life using the

Short Form 36 (SF-36) questionnaire, a widely used and well-validated questionnaire which evaluates

general well-being and functional status.21,22 In this paper we evaluated the impact of three different methods

of repair of large hiatal hernia on changes in SF-36 measured quality of life within the setting of a randomised

controlled trial.

METHODS

In a prospective double-blind randomised controlled trial we compared three laparoscopic methods of repair

of very large hiatus hernias: repair using sutures vs. Biomesh vs. non-absorbable mesh. The full details of the

trial protocol and the objective and clinical symptom outcomes to 12 months follow-up have been reported

elsewhere.15 In the current study we determined the impact of the 3 different methods on SF-36 measured

quality of life at follow-up of up to two years.

56

Chapter 4

SUMMARY OF TRIAL PROTOCOL

The trial was undertaken in 4 centers in Adelaide and Melbourne, Australia, with surgery performed or

supervised by one of 9 surgeons. Individuals undergoing elective laparoscopic repair of a very large hiatus

hernia were enrolled, with a very large hiatus hernia defined as containing at least 50% of the stomach.

Patients were randomised 1:1:1 to repair using sutures vs. repair using sutures reinforced by absorbable mesh

(4 ply Surgisis® ES, Cook Biotech, Indiana, USA) vs. repair using sutures reinforced by non-absorbable mesh

(Timesh®, PFM Medical, Köln, Germany). Patients were blinded to the operation variant and clinical

follow-up was undertaken by a research nurse who was also blinded to the procedure type. Surgical

techniques were standardised, and included full dissection of the hernia sac from the mediastinum, and

complete reduction of the sac’s contents into the abdomen.1,3 Oesophageal lengthening procedures were

not added. The hiatal defect was narrowed using posterior hiatal sutures, supplemented by anterior hiatal

sutures if needed. When randomised to mesh repair, a rectangular piece of mesh (Surgisis or Timesh)

measuring 2-3cm high x 4-5cm wide was placed over the posterior hiatal repair sutures and the hiatal pillars

(but not encircling the oesophagus), and anchored in place using either sutures or a mechanical “tacker”. A

fundoplication was then added. If any procedure varied from the trial allocation, the patient remained in the

allocated group for intention to treat analysis.

FOLLOW-UP AND QUALITY OF LIFE ASSESSMENT

Follow-up using Barium meal X-ray, upper gastrointestinal endoscopy and clinical symptom scores has been

reported elsewhere.15 Symptom scores were obtained with a Visual Analog Scale (VAS) of 0-10, by a

‘blinded’ research nurse using a structured questionnaire 3, 6, 12 and 24 months after surgery. In addition,

patients completed SF-36 Quality of Life (QoL) questionnaires before surgery and at the same follow-up

time points.The SF-36 questionnaire is a widely used and well validated questionnaire,23,24 consisting of 36

items. The questionnaire is summarised in table 1. Thirty five questions contribute to eight subscales, and the

other question stands alone and assesses “Reported Health Transition” (RHT). The scores of the eight sub-

scales and the RHT question are each converted into a 0-100 score. A higher score indicates a better QoL on

that subscale. The subscales can also be converted into two summarising component scales: a “Physical

Component Scale” (PCS) and a “Mental Component Scale” (MCS). The PCS and the MCS have been

validated by Ware et al.22 The component scales provide summary overviews of the SF-36 outcomes. For

calculation of the PCS and MCS, the 8 subscales are standardised using a z-score transformation: population

means are subtracted from the subscale scores, and this difference is divided by the standard deviations of

the norm population. The computed z-scores are then aggregated into the physical and mental component

scales. Each SF-36 subscale z-score is multiplied by its respective physical factor score coefficient and the

eight products are summed. Similarly, this is done for the mental component scale by using the mental factor

score coefficients. The last step is transforming each component score to norm-based scoring. This is

accomplished by multiplying each aggregate component scale score by 10 and adding the resulting product

to 50. To provide a comparable study population for our study, population norm scores were derived from

the Australian population aged 65-74 years, with equal numbers of males and females collected by the

57


4

TABLE 1. PARAMETERS MEASURED BY SHORT-FORM 36

Concept Summary

Physical Functioning Extent to which health limits physical activities

Role Functioning-Physical Extent to which physical healthy interferes with work or other daily activities

Bodily Pain Intensity of pain and effect of pain on normal work

General Health Personal evaluation of health

Vitality Feeling energetic

Social functioning Extent to which physical health or emotions interfere with social activities

Role Functioning-Emotional

Extent to which emotional problems interfere with work or daily activities

Mental Health General mental health

Reported Health Transition

Evaluation of current health compared to one year ago

Australian Bureau of Statistics in 1995. For data analysis, pre- and postoperative PCS and MCS scores as

well as the individual sub-scales were compared for the overall population to assess changes in quality of life

before vs. after hiatal hernia repair, and also for the three trial groups separately to determine differences in

quality of life between the different repair techniques at each follow-up point.

RECURRENCE OF HIATAL HERNIA

As part of the trial protocol, patients underwent objective assessment using upper gastrointestinal

endoscopy and barium meal radiology 6 months after surgery. The presence or absence of a recurrent

hiatus hernia was determined, and patients with a recurrence were classified as symptomatic or

asymptomatic based on symptom scores. Barium meal radiology was reported by radiologists blinded to

the hiatal repair technique, and endoscopy was undertaken in a blinded fashion by upper gastrointestinal

surgeons experienced in assessing anatomy after fundoplication. A recurrent hiatus hernia was defined as any

evidence of the stomach sitting above the level of the diaphragm, irrespective of size. A symptomatic

recurrent hiatus hernia was defined as (1) objective evidence of a recurrent hernia, and (2) heartburn

symptoms scored as 3 or greater using a 0-10 analogue scale (details published elsewhere).15 PCS and MCS

scores determined six months after surgery in patients with a recurrence were compared to scores in patients

without recurrence. PCS and MCS scores in patients with a symptomatic recurrence were compared to

scores in patients with asymptomatic recurrence, and also to those without recurrence.

STATISTICS AND ETHICS

All analyses were performed on an intention-to-treat basis, with all patients remaining in their initial

allocated trial group for data analysis. Parametrically distributed data were analysed using Paired Samples

T-tests, One-way ANOVA tests and Student T-tests. Non-parametric data were analysed using

58

Chapter 4

Kruskal-Wallis tests and Mann-Whitney U-tests. Statistical analyses were performed using IBM’s Statistical

Package for Social Sciences (SPSS), version 19 for Apple Macintosh OS (IBM corp., Armonk, New York,

USA). A P-value of less than 0.05 was considered to be statistically significant.

The protocol for this study was approved by the Human Research Ethics Committee at each participating

hospital. The study was conducted in accordance with the World Medical Association declaration of Helsinki

(revised 1989), and the National Health and Medical Research Council of Australia’s guidelines on human

experimentation.

RESULTS

From July 2006 to September 2012, 126 patients were enrolled in the randomised trial. Forty three were

randomised to undergo hiatal repair with sutures (‘Sutures only’ cohort), 41 to repair with Surgisis (‘Biomesh’

cohort), and 42 to repair with Timesh (‘Timesh’ cohort). As reported elsewhere15 baseline characteristics

were comparable for the three study groups. 115 (91.3%) completed a preoperative SF-36 questionnaire, 113

(89.7%) a questionnaire at 3 months, 116 (92.1%) at 6 months, 114 (90.5%) at 12 months, and 91 (72.2%) at

24 months. Data analysis was undertaken using a paired analysis comparing baseline preoperative scores vs.

postoperative scores. Hence, data was only analysed for patients who completed both the

preoperative questionnaire and at least one of the postoperative questionnaires. This yielded 105 (83.3%)

patients who completed preoperative and 3 months postoperative questionnaires, 106 (84.1%) preoperative

and 6 months postoperative questionnaires, 104 (82.5%) preoperative and 12 months postoperative

questionnaires, and 83 (65.9%) who completed both the preoperative and the 24 months postoperative

SF-36 questionnaire. Completion rates were comparable for the three groups. Missing data were due to

inability to contact patients at specific time points or because patients chose not to complete and return the

questionnaire.

PHYSICAL AND MENTAL COMPONENT SCORE OUTCOMES

Figures 1 and 2 summarise the outcomes for the PCS and MCS scores. For the entire trial cohort the post-op-

erative PCS and MCS scores were significantly higher than the pre-operative scores at all follow-up points

(paired t-tests; p<0.001 for PCS and MCS at each follow-up point). When the trial groups were compared

separately, the PCS scores for all three groups improved significantly at 3, 6, 12 and 24 months postoper-

atively compared to the pre-operative scores (P<0.001-0.044). The follow-up MCS scores were not sig-

nificantly different (P>0.05) to the pre-operative scores at all time points in the ‘Sutures only’ group. In the

‘Biomesh’ group, the MCS score was significantly higher at 12 months (p=0.012, posthoc alpha=0.013) but

not at other time points, whereas in the ‘Timesh’ group the MCS scores were significantly higher at 12 and 24

months, but not at 3 and 6 months (P=0.028 P=0.168, P<0.001, P<0.001 respectively). When the 3 trial

groups were compared at each time point, there were no significant differences between the three groups for

either the PCS or the MCS scores (One-Way ANOVA comparing the three cohorts pre-operative vs.

postoperative scores (3, 6, 12 & 24 months)).

59


4SF-36 SUBSCALE OUTCOMES

The SF-36 subscale outcomes are summarised in figures 3A-3I. There were no significant differences

between the three groups with respect to the pre-operative scores for each of the eight subscales of the

SF-36, with the exception of the ‘sutures only’ vs. the ‘Biomesh’ group for the “Reported Health Transition”

scale (p=0.003, Mann Whitney-U, post-hoc correction alpha=0.017). All eight subscales of the SF-36

improved significantly at 3, 6, and 12 months following surgery, compared to the respective pre-operative

scores. Seven subscales also improved significantly at 24 months, but not the “Role Functioning-Emotional”

scale. There were no significant differences between the three trial groups for scores at any postoperative

follow-up time point.

RECURRENCE

Twenty nine patients were found to a recurrent hiatus hernia (any size) six months after surgery. Nine (31%) of

these were symptomatic. Patients with a recurrent hernia had significantly lower PCS scores, compared to

patients without recurrence (46.9 versus 51.2; p<0.01). For the MCS scores, however, there was no

significant difference for recurrence vs. no-recurrence (48.8 versus 50.7; p=0.213). For the 3-way

comparison of symptomatic versus asymptomatic recurrence versus no recurrence, patients with

symptomatic recurrences had significantly lower PCS scores (p=0.001), whereas for the MCS scores there

was no difference (p=0.453).

Follow-up (months)

2 41 263Preoperative

Mea

n PC

S-sc

ore

58.00

54.00

50.00

46.00

42.00

TimeshBiomeshSutures

FIG. 1 ‘‘PHYSICAL COMPONENT SCALE’’

(PCS) VERSUS FOLLOW-UP

FIG. 2 ‘‘MENTAL COMPONENT SCALE’’

(MCS) VERSUS FOLLOW-UP

Follow-up (months)

241263Pre operative

Mea

n M

CS-

scor

e

58.0 0

54.0 0

50.0 0

46.0 0

42.0 0

TimeshBiomeshSutures

60

Chapter 4

Follow-up (months)

2 41 263Pre-operative

Mea

n R

P-sc

ore

100.00

80.00

60.00

40.00

20.00

. 0 0

Timesh/PTFESurgisis/Biomeshsutures onlyoverall

Cohort

Follow-up (months)


Mea

n BP

-sco

re

100.00

80.00

60.00

40.00

20.00

. 0 0


Cohort

Follow-up (months)


Mea

n PF

-sco

re

100.00

80.00

60.00

40.00

20.00

. 0 0


Cohort

Follow-up (months)


Mea

n G

H-s

core

100.00

80.00

60.00

40.00

20.00

. 0 0


Cohort

A B

C D

Follow-up (months)


Mea

n SF

-sco

re

100.00

80.00

60.00

40.00

20.00

. 0 0


Cohort

Follow-up (months)


Mea

n V

-sco

re

100.00

80.00

60.00

40.00

20.00

. 0 0


Cohort

E F

61


4

DISCUSSION

Laparoscopic approaches are now the standard surgical approach to repair of very large hiatus hernias.

However, the choice of laparoscopic repair techniques can vary between different groups, and consensus

is yet to be reached about the role of mesh vs. sutured repair, synthetic vs. biological meshes, and mesh

configurations - encircling vs. placed posteriorly. In our randomised trial we compared three different ap-

proaches to repair, including sutures vs. synthetic vs. biological mesh. We recently reported no significant

differences for hernia recurrence or clinical outcomes for the three repair methods in the trial,15 and these

results were similar to the late follow-up outcomes reported previously by Oelschlager et al.14 In both our trial

and Oelschlager’s trial the mesh configuration reinforced the hiatal repair posteriorly, a different technique to

that used by Frantzides et al who fully encircled the oesophagus with mesh.13 Our decision to use a posterior

mesh reinforcement technique was based on encouraging early trial outcomes from both Oelschlager et al14

Follow-up (months)


Mea

n R

E-sc

ore

100.00

80.00

60.00

40.00

20.00

. 0 0


Cohort

2 41 263operativePre-

Mea

n M

H-s

core

s

100.00

80.00

60.00

40.00

20.00

. 0 0

Timesh/PTFE

sutures onlyoverall

Cohort

Surgisis/Biomesh

Follow-up (months)


Mea

n R

HT

-sco

re

100.00

80.00

60.00

40.00

20.00

. 0 0


Cohort

I

G HFIG. 3 SF-36 SCORES PER COHORT:A =‘‘PHYSICAL FUNCTIONING’’ (PF) SCORES;B = ‘‘ROLE FUNCTIONING—PHYSICAL’’ (RP) SCORES;C = ‘‘BODILY PAIN’’ (BP) SCORESD = ‘‘GENERAL HEALTH’’ (GH) SCORESE = SF-36 ‘‘VITALITY’’ (V) SCORESF = ‘‘SOCIAL FUNCTIONING’’ (SF) SCORESG = ‘‘ROLE FUNCTIONING—EMOTIONAL’’ (RE) SCORESH = ‘‘MENTAL HEALTH’’ (MH) SCORESI = ‘‘REPORTED HEALTH TRANSITION’’ (RHT) SCORES

62

Chapter 4

and Granderath et al,23 as well as concern that encircling the oesophagus with mesh might increase the risk of

mesh erosion11.

Previous reports from randomised trials,13,14,15,23 and other studies4,6,10 have all focussed on clinical and

objective outcome parameters. However, quality of life is an alternative patient reported outcome, which

reflects the general well-being and the functional status of patients. It also provides complementary

information which informs surgical outcomes, and provides a perspective that might be more relevant to the

individual patient.24 In our randomised trial we used the Short Form 36 (SF-36) questionnaire to assess

general quality of life across various follow-up points. The SF-36 questionnaire is a general quality of life,

rather than a disease specific quality of life questionnaire, and it has been widely validated in a range of

different countries and language groups.25,26 It has been used elsewhere to evaluate quality of life following

laparoscopic surgery, including laparoscopic anti-reflux surgery.20,22

Our current study revealed a general improvement in quality of life following laparoscopic repair of large

hiatus hernias, and this manifested at all follow-up time points from three months to 2 years. Apart from

the “Role Functioning-Emotional” subscale at 24 months follow-up, there was a significant improvement in

all subscales of the SF-36 questionnaire, the two composite scales and the Reported Health Transition at

three, six, 12, and 24 months postoperatively, when compared to the pre-operative scores. This confirms the

effectiveness of laparoscopic repair of large hiatal hernias, and supports other studies that have shown good

clinical and objective outcomes following this surgery.14,15

When comparing quality of life improvements across the different trial cohorts, however, no significant dif-

ferences were seen between the three groups at each follow-up point, although following surgery, the SF-36

scores did improve in a similar fashion in each group. This suggested that each surgical technique (Sutures vs.

Surgisis vs. Timesh) yielded a similar improvement in quality of life, and these results are consistent with the

lack of significant clinical and objective outcome differences that we have reported elsewhere.15

Recurrence of hiatus hernia was the primary outcome of this trial, and this outcome has been reported in

detail elsewhere.15 Analysis of this outcome versus quality of life revealed significantly lower quality of life

scores in patients with a recurrence compared to those without. However, this was seen solely for the physical

component score, not for the mental component score. In the same manner, patients with a symptomatic

recurrence had a poorer quality of life outcome compared to those with an asymptomatic recurrence, again

only for the physical component score. After considering the lack of differences seen for quality of life, clinical

outcomes and objective outcomes for mesh vs. sutured repair of very large hiatus hernia in our randomised

trial, and the lack of significant differences for mesh vs. sutured repair in the 5 year outcomes reported by

Oelschlager,14 we now find it difficult to use mesh for the repair of very large hiatus hernias. It could be argued

that the alternative technique of completely encircling the oesophagus with mesh might yield a different

outcome. However, the data supporting this approach is only from the trial reported by Frantzides et al in

2002 which enrolled 72 patients and then followed them for a median 2.5 years.13 Good results at late

follow-up, or other trials have not been reported, and are needed to confirm the safety of encircling the

oesophagus with polytetrafluoroethylene mesh. Others have reported significant problems with mesh

erosion which we would prefer to avoid.11

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4

Overall quality of life was significantly better at up to two years follow-up after laparoscopic repair of very

large hiatal hernias, with or without posteriorly placed mesh. Whilst the use of mesh did not improve the

quality of life, the overall data from this trial has revealed a sustained improvement in quality of life following

laparoscopic repair of very large hiatus hernia, and this supports the liberal use of surgical repair of large

hiatus hernia in this cohort of patients. However, recurrence of hiatus hernia did impact on physically related

aspects of quality of life. Longer follow-up will be required to confirm the durability of these outcomes.

ACKNOWLEDGEMENTS

This randomised trial was supported by Research Project Grants from the National Health and Medical

Research Council (NHMRC) of Australia - Grant numbers 375111 and 1022722. We are grateful for the as-

sistance of Ms Lorelle Smith, Ms Nicky Carney and Ms Lorraine Sheehan-Hennessy who contributed to data

collection, and Drs Susan Gan and Philip Game who helped with enrolment of patients into the randomised

trial.

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Chapter 4

REFERENCES1. Watson DI, Davies N, Devitt PG, Jamieson GG. Importance of dissection of the hernial sac in laparoscopic surgery for large hiatal hernias. Arch Surg 1999;134:1069-10732. Andujar JJ, Papasavas PK, Birdas T, et al. Laparoscopic repair of large paraesophageal hernia is associated with a low incidence of recurrence and reoperation. Surg Endosc 2004;18:444-447.3. Wijnhoven BP, Watson DI. Laparoscopic repair of a giant hiatus hernia--how I do it. J Gastrointest Surg 2008;12: 1459-1464.4. Hashemi M, Peters JH, DeMeester TR, Huprich JE, Quek M, Hagen JA, et al. Laparoscopic repair of large type III hiatal hernia: objective followup reveals high recurrence rate. J Am Coll Surg 2000;190:553-60.5. Smith GS, Isaacson JR, Draganic BD, Baladas HG, Falk GL. Symptomatic and radiological follow-up after para-esophageal hernia repair. Dis Esophagus 2004;17:279-284.6. Aly A, Munt J, Jamieson GG, Ludemann R, Devitt PG, Watson DI. Laparoscopic repair of large hiatal hernias. Br J Surg 2005;92:648-653.7. Carlson MA, Richards CG, Frantzides CT. Laparoscopic prosthetic reinforcement of hiatal herniorrhaphy. Dig Surg 1999;16:407-410.8. Granderath FA, Carlson MA, Champion JK, Szold A, Basso N, Pointner R, et al. Prosthetic closure of the esophageal hiatus in large hiatal hernia repair and laparoscopic antireflux surgery. Surg Endosc 2006;20:367-379.9. Furnee E, Hazebroek E. Mesh in laparoscopic large hiatal hernia repair: a systematic review of the literature. Surg Endosc 2013;27:3998-4008.10. Hazebroek EJ, Leibman S, Smith GS. Erosion of a composite PTFE/ePTFE mesh after hiatal hernia repair. Surg Laparosc Endosc Percutan Tech 2009;19:175-177.11. Stadlhuber RJ, Sherif AE, Mittal SK, Fitzgibbons RJ,Jr, Michael Brunt L, Hunter JG, et al. Mesh complications after prosthetic reinforcement of hiatal closure: a 28-case series. Surg Endosc 2009;23:1219-1226.12. Oelschlager BK, Pellegrini CA, Hunter J, Soper N, Brunt M, Sheppard B, et al. Biologic prosthesis reduces recurrence after laparoscopic paraesophageal hernia repair: a multicenter, prospective, randomized trial. Ann Surg 2006;244:481-490.13. Frantzides CT, Madan AK, Carlson MA, Stavropoulos GP. A prospective, randomized trial of laparoscopic polytetrafluoro ethylene (PTFE) patch repair vs simple cruroplasty for large hiatal hernia. Arch Surg 2002;137:649-652.14. Oelschlager BK, Pellegrini CA, Hunter JG, et al. Biologic prosthesis to prevent recurrence after laparoscopic paraesopha geal hernia repair: long-term follow-up from a multicenter, prospective, randomized trial. J Am Coll Surg. 2011;213: 461-468.15. Watson DI, Thompson SK, Devitt PG, et al. Laparoscopic repair of very large hiatus hernia with sutures versus absorbable mesh versus non-absorbable mesh:- a randomized controlled trial. Ann Surg 2015;261(2):282-289.16. Kamolz T, Pointner R, Velanovich V. The impact of gastroesophageal reflux disease on quality of life. Surg Endosc 2003;17:1193-1199.17. Kaplan-Machlis B, Spiegler GE, Revicki DA. Health-related quality of life in primary care patients with gastroesophageal reflux disease Ann Pharmacother 1999;33:1032-1036.18. Revicki DA, Wood M, Maton PN, Sorensen S. The impact of gastroesophageal reflux disease on health-related quality of life. Am J Med 1998;104:252-258.19. Kamolz T, Wykypiel H,Jr, Bammer T, Pointner R. Quality of life after laparoscopic antireflux surgery-Nissen fundoplication. Chirurg 1998;69:947-950.20. Granderath FA, Kamolz T, Schweiger UM, Pointner R. Quality of life, surgical outcome, and patient satisfaction three years after laparoscopic Nissen fundoplication. World J Surg 2002;26:1234-1238.21. Ware JE,Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473-483.22. Woodcock SA, Watson DI, Lally C, Archer S, Bessell JR, Booth M, et al. Quality of life following laparoscopic anterior 90 degrees versus Nissen fundoplication: results from a multicenter randomized trial. World J Surg 2006;30:1856-1863.23. Granderath FA, Schweiger UM, Kamolz T, et al. Laparoscopic Nissen fundoplication with prosthetic hiatal closure reduces postoperative intrathoracic wrap herniation: preliminary results of a prospective randomized functional and clinical study. Arch Surg 2005;140:40-48.24. Kamolz T, Granderath F, Pointner R. Laparoscopic antireflux surgery: disease-related quality of life assessment before and after surgery in GERD patients with and without Barrett’s esophagus. Surg Endosc 2003;17:880-885.25. Brazier JE, Harper R, Jones NM, O’Cathain A, Thomas KJ, Usherwood T, et al. Validating the SF-36 health survey questionnaire: new outcome measure for primary care. BMJ 1992;305:160-164.26. Ware JE,Jr, Kosinski M, Bayliss MS, McHorney CA, Rogers WH, Raczek A. Comparison of methods for the scoring and statistical analysis of SF-36 health profile and summary measures: summary of results from the Medical Outcomes Study. Med Care 1995;33(4 Suppl):AS264-79.

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5Laparoscopic hiatal hernia repair in the elderly patient

J.E. OorJ.H. KoetjeD.J. RoksV.B. NieuwenhuijsE.J. Hazebroek

World Journal of Surgery 2016; 40 (6): 1404-1411

68

Chapter 5

ABSTRACT

BACKGROUND Hiatal hernias (HH) are more common among elderly patients, with an increase in

incidence with advancing age. Elderly patients frequently suffer from comorbidity,

causing them to have an increased risk of perioperative mortality and morbidity. The aim

of this study is to assess the safety of this procedure within elderly patients.

METHODS We performed a retrospective analysis of all patients with HH operated between July

2009 and May 2015 at two hospitals in the Netherlands specialised in antireflux surgery

and HH repair. Mortality rates and short- and long term morbidity rates were compared

between patients aged under 70 years and aged over 70.

RESULTS A total of 204 consecutive patients underwent laparoscopic HH repair at our

institutions, of whom 121 were aged under 70 years and 83 were aged over 70. There

was no mortality intraoperatively, nor during 30-days follow-up. Intraoperative

complications occurred in 7 patients aged 70 years and over, with no significant

differences compared to the patients aged under 70. The 30-day morbidity rate did not

significantly differ between the age groups, with an overall postoperative complication

rate of 9.3% . Only length of stay was significantly longer in the elderly patients.

Performing univariate analysis, only the occurrence of intraoperative complications was

associated with 30-day morbidity.

CONCLUSION In the present study, age was not associated with increased 30-day morbidity or

mortality following HH repair. Therefore, in carefully selected patients, age should not

be used as an argument to withhold laparoscopic HH repair.

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Laparoscopic hiatal hernia repair in the elderly patient

5

INTRODUCTION

Hiatal hernias (HH) can be classified into the sliding type (type I), being the most frequent, the ‘true’

para-oesophageal type (type II), which can be further graded according to the severity of the hernia, and the

mixed type (type III), consisting of both a sliding and para-oesophageal component. Type IV hiatal hernias are

characterised by the presence of an upside-down- stomach and possibly omentum or colon. Type IV hernias

pose a challenge to repair due to the large hernial sac, with increased risk of perforation and insufficient tissue

for adequate hiatal closure following dissection.1,2 Hiatal hernias may cause a variety of symptoms, including

obstruction with dysphagia, chest pain, dyspnea, and anemia due to gastric bleeding caused by Cameron

lesions, which can all significantly influence quality of life.

Hiatal hernias, and especially para-oesophageal hernias (POH), are more common among elderly patients,

with an increase in incidence with advancing age.3,4 With the global increase in life expectancy, it can be ex-

pected that the laparoscopic surgeon will more frequently encounter elderly patients suffering from a HH.5

Elderly patients frequently suffer from age-related comorbidity, reflected by an increased American Society

of Anesthesiologists (ASA) score. Compared to younger patients, elderly can therefore be considered to be

more at risk for perioperative complications.

Over the last decades, open repair of HH has been replaced by the laparoscopic approach.6-11 Although

laparoscopy has been shown to be safe in elderly patients, previous studies have reported increased age,

extensive comorbidity and ASA score to be associated with increased morbidity following laparoscopic HH

repair.12,13

Based upon our own experience, we hypothesised that there was no difference in outcome following HH

repair between elderly and younger patients. Therefore, the aim of the present study was to evaluate the

outcome in elderly patients in our centers, with special emphasis on the association between age and 30-day

morbidity.

MATERIAL AND METHODSDESIGN AND PARTICIPANTS

All adult patients who underwent HH repair between July 2009 and July 2015 in two large teaching hospitals

in the Netherlands were analysed. Patients were operated by two gastrointestinal surgeons (EJH,VBN)

specialised in antireflux surgery and HH repair, and who each have performed more than 500 HH repairs and

antireflux procedure. Patients suffering from a type I HH, or who had previously undergone oesophageal or

gastric surgery were excluded.

Details of each patient were retrospectively collected. Based on previous studies, patients were grouped

according to age under 70 years and 70 years and older.13 Comorbidity was grouped into categories that

were separately analysed. Cardiovascular disease included a history of hypertension, coronary artery disease,

arrhythmia, cerebrovascular accident, and peripheral vascular disease. Diabetes mellitus included both type

I and type II diabetes. The presence of chronic obstructive pulmonary disease (COPD) included all types of

GOLD-classifications.

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Chapter 5

DIAGNOSIS

A HH was diagnosed based upon symptoms suggestive of HH confirmed by endoscopy, barium meal

examination and/or a computed tomography (CT) scan.

OPERATIVE TECHNIQUE

Surgical repair compromised full dissection of the hernial sac from the mediastinum and reduction of the

sac’s content into the abdominal cavity, while carefully avoiding vagal or pleural injury. The crural defect was

repaired using posterior non-absorbable hiatal sutures, supplemented by anterior sutures if necessary. A

currently running trial in our institutions compares HH repair using non-absorbable sutures versus sutures

reinforced with non-absorbable mesh (Timesh®, PFM Medical, Köln, Germany). Therefore, participating

patients could have been randomised for sutures reinforced with mesh. Mesh repair was also used when it

was suspected that there was not enough tissue left to adequately approximate the crura following

dissection. Mesh repair involved a sutured posterior hiatal repair followed by placement of a U-shaped piece

of non-absorbable mesh (Timesh®) over the sutures and the hiatal pillars, but not circumferential. The mesh

was anchored with sutures or absorbable tackers to reinforce the repair. Because of the risk of de novo oe-

sophageal acid exposure, all patients underwent an additional partial fundoplication consisting of either a

270 degrees posterior (Toupet) or 180 degrees anterior fundoplication, based upon the surgeon’s

preference.14

POSTOPERATIVE CARE

Postoperative admission to the intensive care unit (ICU) was only performed if clinically necessary. Patients

were allowed oral fluids directly, and soft solid food the next day. Early discharge from the hospital was usual

(day 1 or 2 postoperatively).

OUTCOME

The primary outcome was 30-day morbidity, counting all postoperative events that differed from the

standard postoperative course, including bleeding requiring transfusion or re-intervention, oesophageal

obstruction or stenosis requiring endoscopy, cardiac events, pneumonia, pneumothorax, pulmonary

embolism, deep venous thrombosis, surgical site infection (SSI) and urinary tract infection. Intraoperative

morbidity, 30-day mortality, length of hospital stay and blood loss were secondary outcomes. Follow-up

data were based upon chart review regarding routine postoperative outpatients visits or recurrent visits to the

emergency department (ED).

STATISTICAL ANALYSIS

Statistical analysis was performed after consulting a statistician. The statistical software package SPSS version

22.0 (SPSS, Inc., Chicago, IL, USA) was used. Values are presented as numbers (with prevalence) or median

with range. The Chi square test, or Fisher’s exact test where necessary, were used for comparing binary

variables between groups, and the Mann-Whitney U test for continues variables. Using uni- and multivariate

analysis, the association between 30-day morbidity and different risk factors were analysed. Statistical

significance was defined as p< 0.05.

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5

RESULTSPATIENT CHARACTERISTICS

Between July 2009 and July 2015, 204 consecutive patients underwent HH repair in our institutions. There

were 155 females (76%) and 49 males (24%). Of all patients, mean age at time of surgery was 66.2±11 years.

One hundred and twenty-one patients were under the age of 70, with a mean age of 59.4±9 years, and

83 were aged 70 years and over, with a mean age of 76.0±5.0. Mean follow-up of all patients was 26±16

months. In 28% of the patients, the primary indication for surgery was the presence of obstructive symptoms,

in 24% chest pain, in 22% reflux or regurgitation, in 18% coughing or dyspnea, and in 3% anemia based on

Cameron lesions. The majority of patients (72%) suffered from a mixed-type hernia (type III).

All demographics are summarised in table 1. There were no significant differences in sex, BMI, the number

of patients actively smoking, suffering from COPD, diabetes mellitus (DM) or using systemic corticosteroids

between the two groups.

TABLE 1. BASELINE CHARACTERISTICS OF STUDY GROUPS BASED ON AGE

Age <70 years (n=121) Age ≥70 years (n=83) P-value

Menb 32 (26) 17 (20) 0.39

BMIª 29±4.8 28±4.4 0.43

Active smokerb 10 (8) 5 (7) 0.67

COPDb 19 (16) 12 (14) 0.71

Cardiovascular diseaseb 42 (35) 56 (67) <0.001

ASA-scoreb* 1+2 108 (89) 59 (71) 0.002

3 13 (11) 23 (28)

Previous abdominal surgeryb 57 (47) 43 (52) 0.55

Non-elective surgeryb 8 (7) 7 (8) 0.62

Hernia typeb 2 12 (10) 5 (6) 0.36

3 88 (73) 58 (70)

4 21 (17) 20 (24)

Intrathoracic stomachb^

25-49% 24 (20) 15 (18) 0.70

50-75% 44 (36) 27 (33)

76-100% 48 (40) 41(49)

Approachb Laparoscopic 119 (98) 83 (100) 0.17

Open 2 (2) 0

Conversionb 0 0

Meshb 48 (40) 27 (33) 0.33

BMI = Body Mass Index; COPD = Chronic Obstructive Pulmonary Disease; ASA = American Society of Anesthesiologists physical status score; Data presented as either ª:mean ± standard deviation, orb:number (percentage).*:N missing=1 ; ^: N missing=5.

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Chapter 5

Fifty percent had a history of abdominal surgery. Patients suffering from cardiovascular disease were

significantly more prevalent in the over-70-group compared to the under-70-group (p=<0.001), as were the

patients with ASA-score III (p=0.002). There was no significant difference in the hernia types or size between

the two groups (p=0.36 and 0.70 resp.). Fifteen patients (7.4%) required non-elective surgery, of whom

eight were aged under 70 and seven were aged 70 years and older (p=0.62). All patients presented with

symptoms of obstruction with persistent vomiting and nausea. Of the patients undergoing non-elective

surgery, five (2.4%) required urgent surgery (within 48 hours) because of the suspicion of strangulation or

torsion of the intrathoracic stomach, while the other patients underwent semi-urgent surgery due to

persistent obstruction and vomiting. All patients except for one underwent decompression through

gastroscopy with duodenal tube placement prior to urgent or semi-urgent surgery. Only two patients, both

aged under 70, underwent primary open repair. All other patients underwent laparoscopic repair, in whom

no conversions to open surgery had to be performed. The use of non-absorbable mesh did not significantly

differ between the groups. A 360 degrees Nissen fundoplication was performed in one patient (0.5%), a

posterior 270 degrees Toupet fundoplication in 79 patients (38%), and a 180 degrees anterior

fundoplication in 123 patients (60%).

OUTCOME

There were no intraoperative mortalities. The 30-day mortality rate was 0% for the entire group. Only

one patient (1%) in the over-70-group died more than three months following surgery. This included an

out-of-hospital death secondary to pre-existing heart failure, with subsequent reduced intake, eventually

followed by palliation and death (see table 2). There was no significant difference in mean operating time and

occurrence of intra-operative complications (table 2).

TABLE 2. OUTCOME IN PATIENTS AGED UNDER 70 AND OVER 70

Age <70 years(n=121)

Age ≥70(n=83)

P-value

30-day mortality ª 0 (0) 0 (0) 1.00

Total mortalityª 0 (0) 1 (1) 0.40

Intraoperative complicationsª 5 (4) 7 (8) 0.20

Operative time, minutesb 80 [30-240] 90 [30-213] 0.24

Blood lossª,^ 0-30 cc 76 (63) 67 (81) 0.039

31-100 cc 24 (19) 8 (10)

101-200 cc 10 (8) 4 (5)

201-500 cc 5 (4) 0

>1000 cc 1 (1) 0

30-day morbidityª 10 (8) 9 (10) 0.53

Hospital stay, daysb, x 2.0 [0-9] 2.0 [1-38] 0.007

Recurrent surgeryª 3 (2) 3 (4) 0.69

Data presented as either ª: number (percentage), or b: median [range];*: N missing=14; ^: N missing=9; x: N missing=18.

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5

Intraoperative complications (5.9%) consisted of perforation of the stomach (n=1), bleeding (n=2), atrial

fibrillation (AF) de novo (n=4), capsular tear of the spleen (n=2), pleural tears (n=2), and perforation of the

oesophagus (n=1). Blood loss did significantly differ, with relatively more blood loss in the under-70-group

(p=0.039). Post-operative complications occurred in 19 patients (9.3%). The 30-day morbidity did not

significantly differ between the two groups (8% vs. 11%, p=0.53). Postoperative complications consisted of

mediastinal bleeding requiring surgery (n=1), obstruction (n=3), oesophageal stenosis requiring dilatation

(n=1), pneumonia (n=4),atelectasis (n=2), pulmonary edema (n=2), pulmonary embolus (n=1), cardiac

decompensation (n=1), urinary tract infection (n=2), AF de novo (n=1) and gastro-enteritis (n=1). The length

of hospital stay was significantly longer for older patients compared to the younger patients (p=0.007) (table

2). To compensate for possible bias caused by categorising patients based on age, we re-analysed the above

mentioned outcome variables using 75 years as a cut-off age, after which there were still no significan

differences in outcome between elderly and younger patients apart from a significantly longer hospital stay

for the patients aged 75 and older (see table 3).

TABLE 3. OUTCOME IN PATIENTS AGED UNDER 75 AND OVER 75

Age <75 years (n=159)

Age ≥75 (n=45)

P-value

30-day mortality ª 0 (0) 0 (0) 1.00

Total mortalityª 0 (0) 1 (2) 0.22

Intraoperative complicationsª 7 (4) 5 (11) 0.10

Operative time, minutesb 90 [35-240] 90 [30-150] 0.75

Blood lossª,^ 0-30 cc 108 (68) 35 (83) 0.48

31-100 cc 27 (17) 5 (12)

101-200 cc 12 (8) 2 (5)

201-500 cc 5 (3) 0

>1000 cc 1 (1) 0

30-day morbidityª 15 (9) 4 (9) 0.91

Hospital stay, daysb, x 2.0 [0-13] 2.0 [1-38] 0.004

Recurrent surgeryª 3 (2) 3 (7) 0.56

Data presented as either ª: number (percentage), or b: median [range];*: N missing=14; ^: N missing=9; x: N missing=18.

Furthermore, we analysed the relation between age as a continues variable and 30-day-morbidity using

receiver operating characteristics (ROC) curve analysis, demonstrating low sensitivity and specificity of age as

a risk factor for 30-day morbidity (figure 1).

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Chapter 5

RISK FACTORS ASSOCIATED WITH MORBIDITY

Performing univariate analysis, only the occurrence of intra-operative complications was strongly associated

with 30-day morbidity (table 4). Multivariate analysis could not influence these relations.

TABLE 4. UNIVARIATE ANALYSIS OF RISK FACTORS ASSOCI-

ATED WITH 30-DAY MORBIDITY

Univariate analysis (OR (95%CI))

P-value

Gender 1.3 (0.4-4.0) 0.75

Age ≥70 1.3 (0.5-3.2) 0.54

BMI ≥ 30 1.7 (0.6-4.3) 0.41

Active smoking 1.4 (0.3-6.8) 0.64

COPD 1.4 (0.4-4.5) 0.96

ASA classification III 2.4 (0.9-6.7) 0.09

Previous abdominal surgery 1.0 (0.4-2.5) 0.86

Intra-operative complications 13 (3.7-45.6) <0.001

BMI = Body Mass Index; COPD = Chronic Obstructive Pulmonary Disease; ASA = American Society of Anesthesiologists physical status score.

DISCUSSIONWe found no significant differences in mortality and morbidity rates in elderly patients compared to the

younger patients. This was despite the fact that the elderly group included more patients suffering from

cardiovascular disease and an ASA score of III, being the principal demographic differences between these

two groups in our cohort. There was also no increased rate of intra-operative morbidity or conversions in the

FIG 1. RECEIVER-OPERATING CHARACTERISTICS (ROC) CURVE

OF THE PREDICTIVE VALUE OF AGE FOR 30-DAY MORBIDITY

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5

elderly patients, despite the fact that half of them had a history of abdominal surgery. While some studies

reported equally outcome of foregut surgery in elderly compared to younger patients, others have shown

worse outcome.11,13,15-17 After analysing 19,388 patients undergoing antireflux surgery or HH repair using the

National Surgical Quality Improvement Program (NSQIP) database, Molena et al. found advanced age to be

associated with increased rates of 30-day mortality and morbidity and length of hospital stay.18 They found

higher complication and mortality rates among all patients aged over 70, and report longer mean procedure

times compared to our data (≥150 min. vs. 90-92 min.). However, there are mportant differences in the

casemix of our study compared to the study of Molena et al. which could explain these differences in

morbidity rate and operating time. The population of Molena et al. includes more patients with ASA III-IV

(46.4% vs. 28.0%), a BMI≥30 (48.5% vs. 28.9%), and more patients operated through an open approach

(24.6% vs. 0%) in the over-70-group. Furthermore, no differentiation can be made between patients

operated in low-volume hospitals, with less experience in HH repair, and those who underwent surgery in

specialised centers, such as our hospitals (approximately 80 procedures per year). Larusson et al. specifically

focused on the outcome of laparoscopic HH repair in elderly, based upon a national database.11 In their

analysis, the patients aged over 70 showed a significant higher postoperative morbidity of 24.4%, compared

to the 10.1% found in the younger patients. Both advanced age and ASA-score significantly influenced

mortality and morbidity rates following surgery. They also report a significant higher postoperative morbidity

rate in the over-70-group compared to our results (24.4% vs. 10%), possibly explained by the fact that their

cohort of elderly patients included more patients with an ASA-score of III or IV (41.8% vs. 28%), and more

conversions to laparotomy (4.7% vs. 0%). Overall, morbidity rates following laparoscopic repair of HH in

elderly patients vary among available studies, ranging from 6.7% to 24.4%, which is mainly because of the

heterogeneity of included patients, reflected by differences in ASA scores, urgent versus elective surgery and

conversion rates between studies.12, 13, 15, 17

The only perioperative variable that significantly differed between the two age groups within our cohort

was the mean hospital stay (2.0 days versus 3.6 days), most likely caused by the domestic setting of elderly

patients. We found no association between age and increased mortality or morbidity rates. We believe this

is mainly caused by the following principles implemented in our current selection and treatment strategies

for (elderly) patients suffering from HH. First of all, urgent surgery should be avoided as much as possible.

Only in case of acute intestinal obstruction or strangulation, with the risk of ischemic necrosis, urgent surgery

should be performed19 The risk of incarceration requiring urgent surgery is estimated to be 1% among patients

suffering from a HH.20 Poulose et al. demonstrated that non-elective surgery was associated with a higher

mortality rate and longer hospital stay of 16% and 14.3 days respectively, compared to elective surgery, and

that non-elective surgery was the sole predictor of inpatient mortality in their study.21 In our study, only five

patients (2.4%) underwent urgent surgery, which is a significantly lower rate compared to other studies that

describe higher postoperative morbidity rates.18, 22 In case of acute presentation, decompression using

endoscopy or nasogastric tube placement frequently causes a stable situation allowing elective or semi-

elective surgery.23 In patients who have been symptomatic for prolonged periods of time, with subsequent

reduced dietary intake, elective or semi-elective surgery creates time to optimise the patient’s nutritional

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Chapter 5

status, thereby reducing the risk of postoperative events. Also, optimisation of lung function through

preoperative pulmonary rehabilitation can be organised in patients suffering from COPD. Secondly, we

believe that despite a history of abdominal surgery, laparoscopy should be the primary approach.24 Previous

studies have demonstrated superiority of laparoscopic abdominal surgery in terms of morbidity, post-

operative pain and length of hospital stay compared to conventional abdominal surgery in elderly patients

[25, 26]. These advantages also account for laparoscopic antireflux surgery and HH repair, with lower

morbidity rates and shorter hospital stay following the laparoscopic approach.18,27,28,29 Indeed our data show a

very low overall complication rate, and despite the fact that 50% of the patients reported a history of

abdominal surgery, there were no conversions to open surgery, indicating that it is legitimate to initially

perform laparoscopic surgery in these patients. Since the fundamental work of Nissen and others, dating

back to 1956, concerning the surgical treatment of gastro-oesophageal reflux disease and HH, multiple

techniques and principles concerning HH repair have been established and further developed.24, 30-34 Based

upon the currently available evidence, we believe HH repair should be performed according to the following

principles: (1) complete reduction of the hernial sac, stomach and associated herniated structures with

extensive dissection to optimise oesophageal mobility, (2) primary closure of the crura using non-absorbable

sutures and (3) performing a fundoplication following crural closure.14, 35, 36 Extensive dissection of the hernial

sac is vital for preventing recurrent HH. There are certain limitations of the present study. Due to the retro-

spective design there is a potential for selection bias. Despite the fact that less than 1% of the patients referred

to our two centers did not receive surgical treatment (data not shown), selection bias might have arisen from

selective referral by gastroenterologists, only referring those patients with the best physical condition. We did,

however, include consecutive patients in our analysis, thereby reducing this risk of additional selection bias.

Despite our relatively small sample size compared to national studies, including those using the NSQIP data-

base, we have been able to provide a detailed follow-up of patients, with a low risk of missing data and

underreporting morbidity. The fact that these nationwide databases also include low-volume hospitals could

cause overestimation of the true mortality and morbidity rates of HH repair in elderly patients compared to

surgery performed in high-volume centers. Careful selection of patients, balancing the risks of perioperative

morbidity against functional outcome, and referral to specialised centers experienced with HH repair and

antireflux surgery, could possible reduce perioperative morbidity and lead to better functional outcome in

these potential high risk patients. In the present study, age was not associated with an increased risk of

postoperative mortality and morbidity following HH repair. We can therefore conclude that in a carefully

selected elderly cohort of patients, being operated in specialised centers, laparoscopic HH repair is as safe as

HH repair in younger patients.

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REFERENCES1. Klein T, Semaan A, Kellner M, Ritgen J, Boemers TM, Stressig R. Coincidence of congenital left-sided diaphragmatic hernia and ductus venosus agenesis: Relation between altered hemodynamic flow and lung-to-head-ratio?. J Pediatr Surg Case Rep 2015; 3:245-248 2. Tay CKJ, Teoh HL, Su S. A common problem in the elderly with an uncommon cause: Hypoglycaemia secondary to the Doege-Potter syndrome. BMJ Case Rep 2015 3. Grotenhuis BA, Wijnhoven BPL, Bessell JR, Watson DI. Laparoscopic antireflux surgery in the elderly. Surg Endosc Interv Tech 2015; 22:1807-1812 4. Lal DR, Pellegrini CA, Oelschlager BK. Laparoscopic repair of paraesophageal hernia. Surg Clin North Am 2005; 85: 105-118 5. Evers BM, Townsend CM,Jr, Thompson JC. Organ physiology of aging. Surg Clin North Am 1994; 74:23-39 6. Rezaie A, Hom C, Huang L, Chang C, Chua KS, Pimentel M. Physiologic esophageal length in adults is associated with gender and presence of hiatal hernia but not with age. Gastroenterology 2015; 148:S885 7. Perdikis G, Hinder RA, Filipi CJ, Walenz T, McBride PJ, Smith SL, Katada N, Klingler PJ. Laparoscopic paraesophageal hernia repair. Arch Surg 1997; 132:586-9; discussion 590-1 8. Andujar JJ, Papasavas PK, Birdas T, Robke J, Raftopoulos Y, Gagne DJ, Caushaj PF, Landreneau RJ, Keenan RJ. Laparoscopic repair of large paraesophageal hernia is associated with a low incidence of recurrence and reoperation. Surg Endosc 2004; 18:444-447 9. Targarona EM, Novell J, Vela S, Cerdan G, Bendahan G, Torrubia S, Kobus C, Rebasa P, Balague C, Garriga J, Trias M. Mid term analysis of safety and quality of life after the laparoscopic repair of paraesophageal hiatal hernia. Surg Endosc 2004; 18:1045-1050 10. Sugimoto M, Sahara S, Ichikawa H, Uotani T, Yamade M, Kagami T, Sugimoto K, Furuta T. Efficacy of surgical spinal correction in patients with severe spinal kyphotic deformity for gastroesophageal reflux disease and bowel habi. Gastroenterology 2015; 148:S619 11. Oelschlager BK, Petersen RP, Brunt LM, Soper NJ, Sheppard BC, Mitsumori L, Rohrmann C, Swanstrom LL, Pellegrini CA. Laparoscopic paraesophageal hernia repair: defining long-term clinical and anatomic outcomes. J Gastrointest Surg 2012; 16:453-459 12. Gangopadhyay N, Perrone JM, Soper NJ, Matthews BD, Eagon JC, Klingensmith ME, Frisella MM, Brunt LM. Outcomes of laparoscopic paraesophageal hernia repair in elderly and high-risk patients. Surgery 2006; 140:491-499 13. Larusson HJ, Zingg U, Hahnloser D, Delport K, Seifert B, Oertli D. Predictive factors for morbidity and mortality in patients undergoing laparoscopic paraesophageal hernia repair: Age, ASA score and operation type influence morbidity.World J Surg 2009; 33:980-985 14. Furnee EJ, Draaisma WA, Gooszen HG, Hazebroek EJ, Smout AJ, Broeders IA. Tailored or routine addition of an antireflux fundoplication in laparoscopic large hiatal hernia repair: a comparative cohort study. World J Surg 2011; 35:78-84 15. Trus TL, Laycock WS, Wo JM, Waring JP, Branum GD, Mauren SJ, Katz EM, Hunter JG.Laparoscopic antireflux surgery in the elderly. Am J Gastroenterol 1998; 93:351-353 16. Tedesco P, Lobo E, Fisichella PM, Way LW, Patti MG.Laparoscopic fundoplication in elderly patients with gastroesophageal reflux disease. Arch Surg 2006; 141:289-92; discussion 292 17. Brunt LM, Quasebarth MA, Dunnegan DL, Soper NJ. Is laparoscopic antireflux surgery for gastroesophageal reflux disease in the elderly safe and effective?. Surg Endosc 1999; 13:838-842 18. Molena D, Mungo B, Stem M, Feinberg RL, Lidor AO. Outcomes of operations for benign foregut disease in elderly patients: A National Surgical Quality Improvement Program database analysis. Surgery 2014; 156:352-360 19. Allaix ME, Patti MG. Laparoscopic paraesophageal hernia repair. Surg Laparosc Endosc Percutan Tech 2013; 23:425-428 20. Stylopoulos N, Gazelle GS, Rattner DW. Paraesophageal hernias: operation or observation?. Ann Surg 2002; 236:492- 500; discussion 500-1 21. Poulose BK, Gosen C, Marks JM, Khaitan L, Rosen MJ, Onders RP, Trunzo JA, Ponsky JL. Inpatient mortality analysis of paraesophageal hernia repair in octogenarians. J Gastrointest Surg 2008; 12:1888-1892 22. Louie BE, Blitz M, Orlina J, Farivar A, Aye RW. Repair of symptomatic giant paraesophageal hernias in elderly (> 70 Yrs) patients results in improved quality of life. Gastroenterology 2010; 138:S851 23. Bawahab M, Mitchell P, Church N, Debru E. Management of acute paraesophageal hernia. Surg Endosc Interv Tech 2009; 23:255-259 24. Patti MG, Fisichella PM. Laparoscopic paraesophageal hernia repair. How I do it. J Gastrointest Surg 2009; 13:1728-1732 25. Ballesta Lopez C, Cid JA, Poves I, Bettonica C, Villegas L, Memon MA. Laparoscopic surgery in the elderly patient. Surg Endosc 2003; 17:333-337 26. Weber DM.Laparoscopic surgery: an excellent approach in elderly patients. Arch Surg 2003; 138:1083-1088 27. Nguyen NT, Christie C, Masoomi H, Matin T, Laugenour K, Hohmann S. Utilization and outcomes of laparoscopic versus open paraesophageal hernia repair. Am Surg 2011; 77:1353-1357

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28. Karmali S, McFadden S, Mitchell P, Graham A, Debru E, Gelfand G, Graham J, Martin S, Tiruta C, Grondin S. Primary laparoscopic and open repair of paraesophageal hernias: a comparison of short-term outcomes. Dis Esophagus 2008; 21:63-68 29. Ferri LE, Feldman LS, Stanbridge D, Mayrand S, Stein L, Fried GM. Should laparoscopic paraesophageal hernia repair be abandoned in favor of the open approach?. Surg Endosc 2005; 19:4-8 30. Nissen R. Hiatus hernia and its surgical indication. Dtsch Med Wochenschr 1955; 80:467-469 31. Nissen R .Gastropexy as the lone procedure in the surgical repair of hiatus hernia. Am J Surg 1956; 92:389-392 32. Luketich JD, Nason KS, Christie NA, Pennathur A, Jobe BA, Landreneau RJ, Schuchert MJ. Outcomes after a decade of laparoscopic giant paraesophageal hernia repair. J Thorac Cardiovasc Surg 2010; 139:395-404, 404.e1 33. Auyang ED, Pellegrini CA. How I do it: laparoscopic paraesophageal hernia repair. J Gastrointest Surg 2012; 16:1406-1411 34. Targarona EM, Balague C, Martinez C, Garriga J, Trias M. The massive hiatal hernia: dealing with the defect. Semin Laparosc Surg 2004; 11:161-169 35. Horgan S, Eubanks TR, Jacobsen G, Omelanczuk P, Pellegrini CA. Repair of paraesophageal hernias. Am J Surg 1999; 177:354-358 36. Casabella F, Sinanan M, Horgan S, Pellegrini CA. Systematic use of gastric fundoplication in laparoscopic repair of paraesophageal hernias. Am J Surg 1996; 171:485-489

6Measuring outcomes of laparoscopic antireflux surgery: quality of life versus symptom scores?

J.H. KoetjeV.B. NieuwenhuijsT. IrvineG.C. MayneD.I. Watson

World Journal of Surgery, 2016; 40 (5): 1137-1144

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ABSTRACT

INTRODUCTION Outcome following fundoplication for gastro-oesophageal reflux can be measured

using objective tests, symptom scores, and quality of life (QoL) measures. Which is best

and how these assessments correlate is uncertain. To determine the utility of

assessment measures we compared a general QoL measure (SF-36) and a disease

specific measure (GERD-hr-QoL) with symptom and satisfaction scores in individuals

following fundoplication.

METHODS 329 individuals underwent fundoplication between 2000 and 2015 in 2 centres in

Australia and the Netherlands. Patients were assessed before and 3, 12 and 24 months

after surgery using 10-point Likert-scales to assess heartburn and satisfaction, the SF-36

questionnaire and the GERD-hr-QoL questionnaire. SF-36 scores were converted into

component scores: Physical Component Summary (PCS)-score and Mental

Component Summary (MCS)-score. Correlations between QoL measures and clinical

outcomes were determined.

RESULTS Surgery relieved heartburn (7.0 vs. 0.0 median, P<0.001) and patients were highly

satisfied with the outcome (median 9.0). PCS- and MCS-scores improved after surgery

(PCS 40.9 vs. 46.0, P<0.001; MCS 47.6 vs. 50.3, P=0.027). GERD-hr-QoL scores

also improved after surgery (15.7 vs. 3.7 (P<0.001). Correlations between PCS- and

MCS-scores vs. heartburn and satisfaction-scores were generally weak or absent.

However, correlations between GERD-hr-QoL vs. heartburn and satisfaction scores

were moderate to strong.

CONCLUSION Despite improvements in scores, the SF-36 correlated poorly with clinical outcome

measures, and its use to measure outcome following fundoplication is questioned.

However, the GERD-hr-QoL correlated well with the symptom scores, suggesting this

disease specific QoL measure is a better tool for assessing anti-reflux surgery outcome.

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Measuring outcomes of laparoscopic antireflux surgery: quality of life versus symptom scores?

6

INTRODUCTION

Gastro-oesophageal reflux disease (GORD) is common in Western countries, with up to 40% of individuals

experiencing reflux symptoms at least monthly, and 7% daily.1 A subset with more severe symptoms undergo

a laparoscopic fundoplication. Surgery offers effective reflux control, but can be followed by side effects, and

reflux can recur in some individuals.2 In an attempt to improve outcome a range of fundoplication variants

have been suggested, and many of these have been assessed within randomised trials. When assessing

outcomes, robust comparisons rely on reliable outcome measures. Outcome can be measured using

objective investigations (endoscopy or pH monitoring), standardised clinical assessments and symptom

scores, or Quality of Life (QoL) measures.3,4 Each addresses outcome from a different perspective, and some

outcome measures might be better than others. Unfortunately, it is difficult to get high levels of compliance

with objective measures.3,5 Objective measures such as endoscopy and pH monitoring are invasive and when

used for follow-up, compliance is generally poor, and repeated use of these measures is not practical.

However, standardised symptom scores and quality of life measures are more acceptable to patients and can

be used repeatedly to assess outcome at different time points, and high levels of compliance are achievable.6,7

For more than 20 years we have used standardised clinical assessment scores to measure outcome following

laparoscopic fundoplication, and have found these outcomes correlate well with the findings from objective

studies.2,3,5 We have also used the Short-Form 36 (SF-36), a widely used general QoL measure, and the

GERD-hr-QoL, a GORD health related quality of life measure, to assess quality of life in subsets of patients

enrolled in specific studies.4,8 QoL is an important clinical research outcome.9,10 In 1948 the World Health

Organization defined health as a state of complete physical, mental and social well-being, and not merely the

absence of disease or infirmity.11 Hence, QoL differs from symptom assessment and includes physical,

psychological and social dimensions. However, as it can be a highly subjective outcome, generic and

disease-specific QoL questionnaires have been developed to quantitate QoL so that it can be better assessed

in the research setting.12 As gastro-oesophageal reflux can impact all three dimensions of QoL, assessing QoL

as an outcome for antireflux surgery makes sense.13 QoL can be assessed using general or disease specific

measures. Which method is best applied and how well QoL measures correlate with clinical symptoms is

uncertain. Comparisons of pre- versus postoperative QoL following laparoscopic fundoplication have

confirmed improvement after surgery.9,14,15 However, few studies have assessed how well QoL measures

correlate with symptoms or global satisfaction measures after surgery, and the validity of the SF-36 in this

context is also largely untested. Velanovich et al previously compared the GERD-hr-QoL with the SF-36 in

a small cohort of patients suffering GORD.16 In their study patients were treated with medication or surgery,

and scores were compared at just one random time point. Correlations between the GERD-hr-QoL and

SF-36 with other measures of heartburn and satisfaction pre- and postoperatively, as well as across multiple

time points following antireflux surgery are not clear. Hence, to determine how well different QoL measures

(SF-36 and GERD-hr-QoL) perform as outcome assessment measures following anti-reflux surgery, we

compared QoL outcomes with a widely used symptom-score and global patient satisfaction measure at a

range of pre- and post-operative time points in a much larger cohort of patients.

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METHODSPATIENTS

Patients who underwent laparoscopic fundoplication for GORD between 2000 and 2015 in one of two

cities in Australia (Adelaide) or the Netherlands (Isala, Zwolle) were identified and included in this study.

Data were collected prospectively in both Centres and pooled for analysis.

Patients were included if they;

Underwent laparoscopic fundoplication for objectively proven gastro-oesophageal reflux (pH study showing

excessive acid exposure, or ulcerative oesophagitis at endoscopy)

Had matched symptom scores and QoL scores (SF-36 and/or GERD-hr-QoL scores) collected at at least

one of 3 time points - before surgery (baseline), 3 months after surgery and/or 12 months after surgery

Patients less than 18 years old at surgery, and those whose first operation at our hospitals was a revision

anti-reflux procedure were excluded. Data from Australia was collected within two previously reported

randomised controlled trials; laparoscopic anterior 90º partial vs. Nissen fundoplication,17 and laparoscopic

anterior 180º partial vs. posterior partial vs. Nissen fundoplication.18 The protocol for the second trial was

altered by dropping the Nissen fundoplication arm to improve recruitment, but the patients who underwent

a Nissen fundoplication were still included in the current study. Data from the Netherlands was collected

prospectively as part of a standardised follow-up protocol within the clinical practice of one of the authors

(VBN).

DATA COLLECTED AND FOLLOW-UP METHODS

Collected data included pre-operative and operative details, the SF-36 questionnaire, the GERD-

hr-QoL questionnaire, and symptom scores for heartburn and satisfaction with the surgical

outcome. The symptom scores comprised previously described 10-point Likert scales;

Heartburn - 0 = no heartburn, 10 = severe heartburn; and Satisfaction - 0 = highly unsatisfied with

the outcome of surgery, 10 = highly satisfied.6 Questionnaires were completed before surgery

(SF-36, GERD-hr-QoL, and heartburn score), and at 3, 12 and 24 months (SF-36, GERD-hr-QoL,

heartburn score and satisfaction score). Patients received and completed the questionnaires using

a range of methods; mail, face to face contact at hospital visits, telephone interview, or via e-mail

using a secure online database managing system ‘Research Manager’.

The surgical procedures were standardised within trial protocols and the procedures performed

in the Netherlands were undertaken by a surgeon (VBN) who was trained in anti-reflux surgery in

Adelaide, South Australia. A range of fundoplication variants were used, including Nissen , anterior

900 partial, anterior 1800 partial and posterior partial fundoplication (Toupet). The technical

details for each fundoplication type have been described elsewhere.3,5,17,18

Two QoL measures were used, SF-36 and the GERD-hr-QoL questionnaire. Version 1.0 of the

SF-36 was used. This validated, widely used general QoL questionnaire consists of 36 items. Thirty five of these contribute to eight subscales (Table 1), and the other question stands alone and

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assesses the Reported Health Transition (RHT). The scores of the eight subscales and the RHT-question are

converted into 0-100 scores. A higher score on each subscale indicates a better QoL for that subscale, and a

score of 50 is equivalent to the population median. The subscales can also be converted into two

summarizing component scales: a Physical Component Scale (PCS) and a Mental Component Scale (MCS).

The PCS and the MCS have been validated by Ware et al.19 The component scales provide a more concise

overview of the SF-36 outcomes, and both the subscales and the component scales were calculated and

used in this study. For these calculations we used the population norm scores of the USA 1991, since the

included patients were both Australian and Dutch. This approach is advised in the SF-36 manual.

TABLE 1. SUBSCALES INCLUDED IN THE SHORT FORM-36 (SF-36) QUESTIONNAIRE

Concept Abbreviation Summary

Physical functioning PF Limitations in physical activities because of health problems

Social functioning SF Limitations in social activities because of physical or emotional problems

Role functioning - physical RP Limitations in usual role activities (work or other daily activities) because of physical health problems

Bodily pain BP The effect on pain on work and the severity of pain

General mental health MH Psychological distress and well-being

Role functioning - emotional RE Limitations in usual role activities because of emotional problems

Vitality V Energy and fatigue

General health GH Perception of general health

Reported health transition RHT Current health compared to the situation one year before

GORD health-related quality of life was assessed by using the GERD-hr-QoL questionnaire. This is a disease

specific, validated questionnaire, that consists of nine questions. Each question can be scored from 0 to

5. This questionnaire has been used in previously published studies, and often in conjunction with the SF-

36.20,21


Analysis compared both SF-36 derived outcomes and GERD-hr-QoL outcomes vs. clinical symptom

outcomes. Statistical analysis was performed using IBM’s Statistical Package for Social Sciences (SPSS),

version 22 for Apple Macintosh OS (IBM corp., Armonk, New York, USA). Parametrically distributed

continuous data are summarised as mean ± standard deviation (SD). Non-parametric continuous data are

summarised as median with interquartile ranges (IQR). Categorical data are summarised as frequencies with

percentages. The Paired Samples T-tests was used to compare parametrically distributed paired continuous

data. Non-parametrically distributed paired continuous data sets were compared using the Wilcoxon Signed

Rank test. The Independent Samples T-test was used to compare unpaired parametrically distributed

continuous data, and unpaired non-parametrically distributed continuous data was assessed using the

Mann-Whitney-U tests. Post-hoc analyses were performed using the Holm-Bonferonni correction. The

Chi-square test or Fisher’s exact test were used to compare proportions of categorical data. Correlations

between non-parametrically distributed continuous data sets were determined using Spearman’s Rank

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Chapter 6

correlation test, and presented as Spearman rho correlation coefficient (rs). A r

s less than 0.40 was

considered to be weak, rs of 0.40 to 0.59 to be a moderate correlation, r

s>0.60 to be strong, and r

s>0.80 to

be very strong. Correlations with rs>0.35 are considered to be of clinical importance, as for these correlations

the association exceeds 10%. A P-value of <0.05 was considered statistically significant. However, to reduce

the chance of a type 1 error due to a large number of tests, we only considered a P-value of <0.01 to be

statistically significant for the correlation analyses. All calculated P-values were two-sided.

ETHICAL APPROVAL

Data was collected with approval of the human research ethics committees of the participating hospitals. All

patients provided written informed consent and agreed to the use of their data for research.

RESULTS329 patients met the study inclusion criteria. 276 had matched preoperative data, 219 had matched data at 3

months, 141 at 12 months and 115 at 24 months after surgery, for paired analyses.

BASELINE CHARACTERISTICS

Table 2 summarises the baseline characteristics of the patients included in the study. Age, height, weight and

BMI were at the day of surgery. Mean age in the Australian cohort was older than in the Dutch cohort.

Gender distribution was similar for both cohorts. The Dutch patients were significant taller than the

Australian patients, and as body weight was similar, the BMI was lower in the Dutch cohort. The

fundoplication types differed for the 2 cohorts, with the Dutch cohort mainly undergoing an anterior 180º

partial fundoplication (80.2%), and no Dutch patients undergoing a posterior partial or an anterior 90º

partial fundoplication. Re-operation rates were similar for both cohorts. The Dutch patients reported a higher

baseline heartburn score than the Australian patients (median 8.0 vs. 5.0), and also a higher score

postoperative. Heartburn scores in the overall group, as well as individually in both cohorts, improved

significantly following surgery (P<0.001). Patients from both Centres were highly satisfied with the outcome

of their surgery (median satisfaction-score 9.0 at 24 months).

SF-36 PHYSICAL COMPONENT SCALE AND MENTAL COMPONENT SCALE

Table 3 summarises the scores for the PCS and the MCS at the different time points. Compared to pre-

operative scores there was a significant increase in PCS-score at three, 12 and 24 months (P<0.001). The

increase in the MCS-score was also significant at three months (P=0.002) and 24 months (P=0.027)

postoperative, but not at 12 months (P=0.575). The MCS-score was below the population norm (score of

50) before surgery, but just above the population norm at both at 3 and 24 months postoperative. However,

the PCS-score remained below the population norm score both before and after surgery.

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TABLE 2. BASELINE CHARACTERISTICS

Overall cohort (n=329)

Australian cohort (n=167)

Dutch cohort (n=162)

P-value

Age1 50.15 (13.31) 50.61 (12.54) 49.69 (14.07) 0.5364

Gender² Male 162 (49.2%) 84 (50.3%) 78 (48.1%) 0.6965

Female 167 (50.8%) 83 (49.7%) 84 (51.9%)

Height1 1.71 (0.10) 1.68 (0.10) 1.74 (0.10) <0.0014

Weight1 82.27 (15.55) 82.63 (13.46) 81.95 (17.19) 0.7054

BMI1 28.02 (4.84) 29.28 (4.31) 26.99 (5.02) <0.0014

Type of fundoplication²

Anterior 90º partial 58 (17.6%) 58 (34.7%) 0 (0%) <0.0015

Anterior 180º partial 154 (46.8%) 24 (14.4%) 130 (80.2%)

Posterior partial 39 (11.9%) 23 (13.8%) 16 (9.9%)

Nissen 78 (23.7%) 62 (37.1%) 16 (9.9%)

Re-operation² 24 (7.3%) 13 (7.8%) 11 (6.8%) 0.8805

Heartburn3 Pre-op 7.0 (4.0) 5.0 (5.0) 8.0 (2.0) <0.0016

3 months 0.0 (2.0)* 0.0 (0.0)* 1.0 (2.0)* <0.0016

12 months 0.0 (2.0)* 0.0 (2.0)* 1.0 (3.0)* <0.0016

24 months 0.0 (3.0)* 0.0 (2.0)* 2.0 (2.0)* <0.0016

Satisfaction3 3 months 9.0 (3.0) 9.25 (2.0) 8.0 (3.0) 0.0036

12 months 9.0 (3.0) 9.25 (2.0) 8.0 (3.75) 0.0396

24 months 9.0 (3.0) 9.0 (3.0) 8.0 (3.75) 0.1606

BMI = Body Mass Index; Data presented as either 1mean (standard deviation), 2number (percentage), or 3median (interquartile range).P-values are for comparisons between the Australian and Dutch cohorts; 4 P-value using independent samples T-Test; 5 P-value using Chi-Square Test; 6 P-value using Mann-Whitney-U-Test; * = Significant (P<0.001) difference for comparison of pre-operative vs. postoperative scores using the Wilcoxon Signed Rank Test.

TABLE 3. MEAN PHYSICAL AND MENTAL COMPONENT SCORES FOR THE OVERALL POPULATION

Pre-operative (n=276) 3 months (n=219) 12 months (n=141) 24 months (n=115)

PCS 40.9 (9.8) 44.5 (10.9)** 44.7 (11.4)** 46.0 (11.5)**

MCS 47.6 (11.9) 50.3 (9.8)* 48.7 (11.2) 50.3 (10.3)*

Data presented as mean (SD). PCS = Physical Component Scale; MCS = Mental Component Scale; *P<0.05 for Pre-operative vs. post-operative QoL-score (Paired samples T-Test); **P<0.001 for Pre-operative vs. post-operative QoL-score (Paired samples T-Test)

GERD-HR-QOL

Table 4 summarises the scores for the GERD-hr-QoL at the different time points. Compared to

preoperative scores there was a significant improvement (decrease) in the GERD-hr-QoL score at three, 12,

and 24 months (P<0.001).

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TABLE 4. MEAN GERD-HR-QOL SCORES FOR THE OVERALL POPULATION

Pre-operative (n=276) 3 months (n=219) 12 months (n=141) 24 months (n=115)

GERD-hr-QoL 15.7 (8.3) 3.2 (4.7)* 2.6 (4.9)* 3.7 (3.8)*

Data presented as mean (SD). *P<0.001 for Pre-operative vs. post-operative score (Paired samples T-Test).

CORRELATIONS BETWEEN SF-36 AND SYMPTOM SCORES

Correlations between the heartburn-score and the satisfaction-score vs. the PCS- and MCS-scores are

summarised in Table 5. Before surgery, the majority of patients reported high heartburn scores, but a wide

variation in PCS- and MCS-scores. Following surgery, the majority of patients reported low heartburn scores,

and again a wide variation across the PCS- and MCS-scores. Using the satisfaction score, the majority of

patients were highly satisfied with results of the surgery, but also with a wide variation seen in PCS- and MCS-

scores. More dissatisfied patients (low satisfaction grade <3) also reported highly variable PCS- and MCS-

scores. The Spearman rho correlation coefficient for the tested correlations did not exceed 0.314, indicating

that any statistically significant correlation between the variables was either clinically weak or absent. For the

PCS-score statistically significant (but clinically weak) correlations were seen with both the heartburn and

satisfaction scores at 3 months postoperative. For the MCS-score a statistically significant correlation was

seen with the Satisfaction-score at 3 months, but this was also clinically weak.

TABLE 5. CORRELATIONS BETWEEN SF-36 COMPONENT SCORES AND CLINICAL OUTCOME SCORES

PCS MCS

rs

P-value rs

P-value

0-10 Heartburn score Preoperative (n=262) -0.124 0.046 -0.106 0.088

3 months (n=200) -0.231 0.001 -0.067 0.347

12 months (n=131) 0.032 0.716 0.087 0.324

24 months (n=110) -0.087 0.364 -0.054 0.573

0-10 Satisfaction score 3 months (n=211) 0.314 <0.001 0.237 0.001

12 months (n=137) 0.066 0.446 0.083 0.337

24 months (n=110) 0.231 0.015 -0.025 0.795

PCS = Physical Component Scale; MCS = Mental Component Scale. rs = Spearman rho correlation coefficient. P-values indicate statistical

significance of Spearman Rank’s correlation test outcomes for each correlation.

Table 6 summarises correlations between the symptom scores and SF-36 subscales. Statistically significant

correlations were seen between the satisfaction score and all SF-36 subscales except “Role Emotional” at

3 months follow-up. Statistically significant correlations were seen between the satisfaction score and the

“General Health” and “Reported Health Transition” scores at 12 and none at 24 months follow-up.

No correlations were identified with any other subscales. The correlations identified with the satisfaction

score were all clinically weak (rs<0.3), except for the “Social Functioning”, “General Health”, and “Reported

Health Transition” scores for which moderate correlations were identified. Statistically significant correlations

were seen between the heartburn score and “Social Functioning”, “Bodily Pain”, “General Health” and

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“Reported Health Transition” at 3 months follow-up. All of these correlations were clinically weak (rs<0.3).

No correlations with heartburn were identified for any subscale measured before surgery, at 12 months and at

24 months after surgery.

TABLE 6. CORRELATIONS BETWEEN SF-36 SUBSCALES AND CLINICAL OUTCOME SCORES

PF SF RE BP MH RP V GH RHT

0-10 Heartburn score

Preop (n=262)

-0.109 -0.146 -0.124 -0.010 -0.068 -0.138 -0.119 -0.151 -0.107

3 months (n=200)

-0.084 -0.234* -0.036 -0.195* -0.071 -0.159 -0.078 -0.226* -0.246**

12 months (n=131)

0.032 0.121 0.068 0.066 0.058 0.038 0.149 -0.129 -0.159

24 months (n=110)

-0.111 -0.071 -0.008 -0.057 -0.110 0.012 -0.053 -0.176 -0.266

0-10 Satisfaction score

3 months (n=211)

0.186* 0.323** 0.140 0.236* 0.209* 0.274** 0.280** 0.328** 0.562**

12 months (n=137)

0.009 0.032 0.036 0.097 0.069 -0.043 0.038 0.264* 0.418**

24 months (n=110)

0.178 0.108 -0.126 0.187 0.049 0.083 0.131 0.212 0.331

All data is Spearman rho correlation coefficients; *P<0.01, **P<0.001. PF = Physical functioning, SF = Social functioning, RE = Role functioning - emotional, BP = Bodily pain, MH = General mental health, RP = Role functioning - physical, V = Vitality, GH = General health, RHT = Reported health transition.

CORRELATIONS BETWEEN GERD-HR-QOL AND SYMPTOM SCORES

Table 7 summarises the correlations between the heartburn-score and the satisfaction-score vs. the

GERD-hr-QoL-scores. Significant correlations were identified for all scores at all time points. Postoperative

scores for heartburn correlated moderately or strongly with the GERD-hr-QoL and were likely to be clinical

significant. There was a moderate correlation between Satisfaction at 3 and 24 months postoperative vs.

GERD-hr-QoL, and this also exceeded the threshold for clinical significance. Preoperative heartburn scores

vs. preoperative GERD-hr-QoL scores, and satisfaction scores vs. GERD-hr-QoL score at 12 months postop-

erative correlated weakly.

DISCUSSIONAs GORD is a chronic disease that impairs quality of life, formal quality of life measurement seems to be an

appropriate method for assessment of surgical outcomes.10 The aim of antireflux surgery is to fix each

individual’s symptoms, and at the same time not add any new problem or side effect. An important outcome

for surgery is control of reflux symptoms, and this can be quantitated using disease specific symptom

questionnaires.3 However, focussing on reflux symptoms ignores post-fundoplication side effects which can

also impact on the outcome of surgery. To address this, more general measures of satisfaction such as the

Likert satisfaction scale or a general QoL assessment are needed. Previous studies have shown that patients

suffering gastro-oesophageal reflux report a poorer quality of life than a matched healthy population, with

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TABLE 7. CORRELATIONS BETWEEN GERD-HR-QOL SCORES AND CLINICAL OUTCOME SCORES

GERD-hr-QoL

rs

P-value

0-10 Heartburn score Preoperative (n=262) 0.360 <0.001

3 months (n=200) 0.581 <0.001

12 months (n=131) 0.464 0.001

24 months (n=110) 0.745 <0.001

0-10 Satisfaction score 3 months (n=211) -0.539 <0.001

12 months (n=137) -0.359 0.007

24 months (n=110) -0.503 0.009

rs = Spearman rho correlation coefficient.

P-values indicate statistical significance of Spearman Rank’s correlation test outcomes for each correlation.

decreased scores for both the physical and mental components of the SF-36 questionnaire.13,22 This suggests

that the SF-36 should be a valid method for outcome assessment after antireflux surgery, and other studies

have shown improvements in SF-36 scores following laparoscopic anti-reflux surgery.6,14,15 Other studies,

however, have used disease specific QoL assessment, with the GERD-hr-QoL frequently used to evaluate the

outcome of laparoscopic anti-reflux surgery. In our study QoL, quantified by the PCS- and MCS-scores of

the SF-36, improved significantly following laparoscopic fundoplication, as did QoL measured by the GERD-

hr-QoL. Heartburn scores also fell significantly following surgery, and anti-reflux surgery was associated with

a high rate of satisfaction at 3, 12 and 24 months postoperative. These outcomes are similar to those

reported in previous randomised trials and outcome studies.8,15,23 In our current study, the MCS-scores 3 and

24 months after surgery were equivalent to the ‘healthy population’ norms, but the PCS-scores remained

below this norm score, mainly due to lower scores on the Vitality, General Health and Bodily Pain subscales.

Whilst it is expected that these subscales will be impaired during early follow-up, it is to be expected that

these scores should reach norm-scores by 12 to 24 months after surgery. This outcome is somewhat at odds

with the high level of heartburn control and high level of satisfaction with the outcome of surgery.

In general, clinically significant correlations between the SF-36 outcomes and the heartburn-score were not

identified. This suggests a poor relationship between general quality of life measured by the SF-36, and

reflux symptoms. More correlations between the SF-36 component scores and the subscales were seen with

the satisfaction score. However, most of the correlations were still only clinically weak, and largely seen at 3

months, but not at 12 or 24 months follow-up. Somewhat stronger correlations were seen at 3 months for

Satisfaction vs. “Reported Health Transition” (rs=0.562), “General Health” (r

s=0.328), “Social Functioning”

(rs=0.323) and the “Physical Composite Scale” (r

s=0.314), and at 12 and 24 months for Satisfaction vs.

“Reported Health Transition”. This might indicate some validity for the SF-36 scores as a global outcome

measure, rather than as a disease specific measure, but the magnitude of the correlations should be

recognised to be modest at best. In comparison, the GERD-hr-QoL correlated more strongly with the

Heartburn scores, and also with the Satisfaction scores at all time points. Although the preoperative

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correlation between Heartburn score and GERD-hr-QoL was somewhat weaker, the postoperative

correlations were certainly strong, and likely to be indicative of clinical symptom outcomes. This almost

certainly reflects the more disease specific questions used in the GERD-hr-QoL questionnaire, which focus

on symptoms like heartburn, rather than more generic QoL issues. A reasonable conclusion to draw from our

study is that generic quality of life measures such as the SF-36 are not specific enough to be used as robust

outcome assessment tools following surgery for gastro-oesophagal reflux, whereas disease specific measures

such as the GERD-hr-QoL questionnaire appear better suited to assessment of outcome following antireflux

surgery, and correlate better with validated symptom scores.12 In general, the disease specific measures such

as the GERD-hr-QoL appear to grade the severity of outcomes such as Heartburn and other reflux

symptoms, in a similar manner to the Likert Heartburn score used in the current study. A difficulty with our

current study is that there is no agreed “gold standard” for assessment of outcome after anti-reflux surgery.

We have, however, reported extensively using the Likert scores applied in the current study, and have shown

a good correlation between these scores and clinically meaningful outcomes, as well as with the outcomes

from objective measures such as pH monitoring.3,5 It seems likely therefore, that the conclusion that the SF-

36 performs poorly for the assessment of outcomes following surgery for reflux is valid, and a disease specific

QoL measure such as the GERD-hr-QoL would be a better choice for outcome assessment.As the current

study combined cohorts from two different countries, there are differences in the populations undergoing

surgery, based on case selection and other factors. These differences account for the differences highlighted

in Table 2. Obesity is a known risk factor for reflux, and the higher BMI in the Australian cohort might have

adversely influenced the preoperative heartburn scores, but the converse was seen. Differences in pre-op-

erative heartburn scores might reflect earlier referral for surgery in Australia where fundoplication is a more

common procedure than in the Netherlands. However, even though there were differences between the 2

cohorts included in the study, it is unlikely that these differences impacted on the study outcomes, as data

were pooled and outcomes were not compared between countries. In conclusion, whilst quality of life and

heartburn improved following anti-reflux surgery, and patients expressed high rates of satisfaction, the SF-36

questionnaire performed poorly as an outcome assessment tool in this context. This is probably because the

SF-36 is a questionnaire which assesses generic quality of life, and it is not specific enough to be used for

reliable measurement of outcome after laparoscopic anti-reflux surgery. In general, correlations between clin-

ical outcome scores and SF-36 parameters were either poor or absent, suggesting that the changes in SF-36

scores did not consistently reflect disease specific outcomes following surgery. In contrast, the disease specif-

ic GERD-hr-QoL questionnaire performed much better, and along with disease specific clinical assessments,

is recommended for assessment of outcome following surgery for gastro-oesophageal reflux.

ACKNOWLEDGEMENTSWe are grateful for our colleagues who contributed patients to this study, and for the assistance of Ms Lorelle

Smith and Ms Nicky Ascott who maintained the database and obtained the SF-36 follow-up for the

Australian cohort. Follow-up of the Australian cohort was supported by Research Project Grants from the

National Health and Medical Research Council (NHMRC) of Australia - Grant numbers 375111 and 1022722.

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REFERENCES

1. Camilleri M, Dubois D, Coulie B, Jones M, Kahrilas PJ, Rentz AM, et al. Prevalence and socioeconomic impact of upper gastrointestinal disorders in the United States: results of the US Upper Gastrointestinal Study. Clin Gastroenterol Hepatol 2005;3:543-552.2. Engström C, Cai W, Irvine T, Devitt PG, Thompson SK, Game PA, Bessell JR, Jamieson GG, Watson DI. Twenty years of experience with laparoscopic antireflux surgery. Br J Surg 2012;99:1415-1421.3. Watson DI, Pike GK, Baigrie RJ, Mathew G, Devitt PG, Britten-Jones R & Jamieson GG. Prospective double blind random ized trial of laparoscopic Nissen fundoplication with division and without division of short gastric vessels. Ann Surg 1997;226:642-652.4. Koetje JH., Irvine T, Thompson SK, Devitt PG, Woods SD, Aly A, Jamieson GG, Watson DI. Quality of life following repair of large hiatal hernia is improved but not influenced by use of mesh: Results from a randomized controlled trial. to World J Surg 2015;39:1465-1473.5. Watson DI, Jamieson GG, Pike GK, Davies N, Richardson M, Devitt PG. Prospective randomized double-blind trial between laparoscopic Nissen fundoplication and anterior partial fundoplication. Br J Surg 1999;86:123-130.6. Yang H, Watson DI, Lally CJ, Devitt PG, Game PA, Jamieson GG. Randomized trial of division versus non-division of the short gastric vessels during laparoscopic Nissen fundoplication – 10 year outcomes. Ann Surg 2008;247:38-42.7. Cai W, Watson DI, Lally CJ, Devitt PG, Game PA, Jamieson GG. Ten-year clinical outcome of a prospective randomized clinical trial of laparoscopic Nissen versus anterior 180° partial fundoplication. Br J Surg 2008;95:1501-1505.8. Woodcock SA, Watson DI, Lally C, Archer S, Bessell JR, Booth M, et al. Quality of life following laparoscopic anterior 90 degrees versus Nissen fundoplication: results from a multicenter randomized trial. World J Surg 2006;30:1856-1863.9. Kamolz T, Wykypiel H, Jr, Bammer T, Pointner R. Quality of life after laparoscopic antireflux surgery--Nissen fundoplication. Chirurg 1998;69:947-950.10. Kamolz T, Pointner R, Velanovich V. The impact of gastroesophageal reflux disease on quality of life. Surg Endosc 2003;17:1193-1199.11. Preamble to the Constitution of the World Health Organization as adopted by the International Health Conference, New York, 19 June - 22 July 1946; signed on 22 July 1946 by the representatives of 61 States (Official Records of the World Health Organization, no. 2, p. 100) and entered into force on 7 April 1948.12. Velanovich V, Vallance SR, Gusz JR, Tapia FV, Harkabus MA. Quality of life scale for gastroesophageal reflux disease. J Am Coll Surg 1996;183:217-224.13. Revicki DA, Wood M, Maton PN, Sorensen S. The impact of gastroesophageal reflux disease on health-related quality of life. Am J Med 1998;104:252-258.14. Glise H, Hallerback B, Johansson B. Quality-of-life assessments in evaluation of laparoscopic Rosetti fundoplication. Surg Endosc 1995;9:183-8.15. Granderath FA, Kamolz T, Schweiger UM, Pointner R. Quality of life, surgical outcome, and patient satisfaction three years after laparoscopic Nissen fundoplication. World J Surg 2002;26:1234-1238.16. Velanovich V. Comparison of generic (SF-36) vs. disease-specific (GERD-HRQL) quality-of-life scales for gastroesophageal reflux disease. J Gastrointest Surg. 1998;2:141-5.17. Watson DI, Jamieson GG, Lally C, Archer S, Bessell JR, Booth M, Cade R, Cullingford G, Devitt PG, Fletcher DR, Hurley J, Kiroff G, Martin C, Martin IJG, Nathanson LK, Windsor J. Multicentre prospective double blind randomized trial of laparoscopic Nissen versus anterior 90 degree partial fundoplication. Arch Surg 2004;139:1160-1167.18. Daud WMBW, Thompson SK, Jamieson GG, Devitt PG, Martin IJG, Watson DI. Randomized controlled trial of laparoscopic anterior 180° partial vs. posterior 270° partial fundoplication. ANZ J Surg (2014) DOI: 10.1111/ans.12476. 19. Ware JE, Jr, Kosinski M, Bayliss MS, McHorney CA, Rogers WH, Raczek A. Comparison of methods for the scoring and statistical analysis of SF-36 health profile and summary measures: summary of results from the Medical Outcomes Study. Med Care 1995;33 (4 Suppl):AS264-79.20. Tosato F, Marano S, Mattacchine S, Luongo B, Mingarelli V, Campagna G. Quality of life after Nissen-Rossetti fundoplication. Surg Laparosc Endosc Percutan Tech 2012;22:205-209.21. Rossetti G, Limongelli P, Cimmino M, Napoletano D, Bondanese MC, Romano G, Pratilas M, Guerriero L, Orlando F, Conzo G, Amato B, Docimo G, Tolone S, Brusciano L, Docimo L, Fei L. Outcome of medical and surgical therapy of GERD: predictive role of quality of life scores and instrumental evaluation. Int J Surg 2014;12:112-116.22. Kamolz T , Pointner R, Velanovich V. The impact of gastroesophageal reflux disease on quality of life. Surg Endosc 2003;17:1193-1199.23. Korolija D, Sauerland S, Wood-Dauphinee S, Abbou CC, Eypasch E, Caballero MG, et al. Evaluation of quality of life after laparoscopic surgery: evidence-based guidelines of the European Association for Endoscopic Surgery. Surg Endosc 2004;18:879-897.

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7Online collection of Patient Reported Outcome Measures: an effective method for follow-up of benign surgery

Oral presentation at Chirurgendagen 2015, Veldhoven

Poster presentation at NVEC congres 2015, Amsterdam

J.H. Koetje G.M. van DamJ. DilleV.B. Nieuwenhuijs

Submitted

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ABSTRACT

BACKGROUND: Long-term follow-up for benign surgery is of importance, but due to small

administrative and logistic capacity not available. This study describes the results of our

online data collection system used in a cohort of patients after antireflux surgery. We

compared the online system with the previously used paper based data collection.

METHODS: This study included 294 patients following laparoscopic antireflux surgery. It compares

response rates and completeness of collected data between a group that uses an online

data collection system, using automated e-mails, and a group that completed data on

paper. Also, improvement and satisfaction after surgery are compared between both

methods of data collection.

RESULTS: Response rates with online data collection were 86.3%-90.4%. This is significant

higher when compared to collection with paper questionnaires (11.9%-66.4%;

P<0.001). Completeness of collected data is higher with the online system as well

(94.9%-99.3% vs. 54.5%-75.0%; P<0.05). Improvement of GORD-related quality of

life, improvement of dysphagia complaints, satisfaction of surgery and the number of

patients that would undergo this operation again (based on their postoperative

situation) are equal in the online and paper group.

CONCLUSIONS: Online follow-up leads to high response rates and high completeness of data. It is a user

friendly way to collect data in large cohorts of patient with benign pathology. This data

can be used to inform patients on the surgeon or hospital results for a specific treatment

and is useful for healthcare providers to evaluate treatments.

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Online collection of Patient Reported Outcome Measures: an effective method for follow-up of benign surgery

7

INTRODUCTIONPatient Reported Outcome Measures (PROMs) are increasingly used as valuable parameters of quality of

medical care.1-4 The main advantage of PROMs is that the patient’s opinion is not interpreted or influenced

by a researcher or clinician.5 For malignant diseases, data collection and evaluation of care is an integrated

and established part of clinical practice. Funded by health care companies, it is well-organized, validated and

reliable according to (inter-) national guidelines and databases.6-13

However, for benign pathology, follow-up after treatment is often not available. In benign surgery the balance

of surgical harm and change in quality of life is more important, since surgery is not lifesaving. The outcomes

of treatments could be registered, amongst others to inform other patients. The increasing demand of clinical

results in health care by National Health Agencies and insurance companies to justify hospital contracts may

be another interesting reason to report outcome of treatment in benign disease. 14 Active follow-up after

benign surgery carries a considerable high logistic and administrative burden, making it often impossible

to follow patients yearly, notwithstanding the impact on costs of data managers and hospital visits. For this

reason an unmet need exists for alternative methods for follow-up. As a consequence, we have attempted to

provide potential solutions for this problem.

In our practice, we have chosen to use routine questionnaires, printed on paper, and handed these to the

patients during their visit to the outpatient clinic before and after laparoscopic antireflux surgery or sent the

questionnaires by regular mail. These data were collected prospectively for all patients on yearly base, and

consisted of questionnaires, both validated health-related, quality of life and disease specific as well as

questions to evaluate quality of care. Since not all questionnaires were completed by all patients and

therefore often not useable, we were searching for a better follow-up method. In our hospital an online data

collection system was developed (Research Manager®) with an option for online questioning per e-mail. We

hypothesised that this online follow-up would lead to a better response rate and more complete data. In this

study we describe the response rate and completeness of the collected data between the online and ‘offline’

questionnaires in a large cohort of patients after laparoscopic antireflux surgery.

MATERIAL AND METHODSAll patients that were planned for antireflux surgery suffering gastro-oesophageal reflux disease (GORD),

hiatal hernia oeophagei (HHO) or achalasia in our hospital were asked to join the follow-up program. Patients

who were mentally incapable to fill in questionnaires, younger than 18 years, incapable to speak the Dutch

language or patients that were diagnosed for a different disease during preoperative investigations or during

surgery were excluded. QoL measurements consisted of one preoperative questionnaire, and six

postoperative questionnaires. The first postoperative questionnaire was send three months postoperative,

the following questionnaires were send one year up until five years postoperative. Patients were seen in the

outpatient clinic four weeks and three months postoperative, and again if needed. All patients received yearly

telephone calls up until five years postoperatively.

SURGICAL PROCEDURES

All surgical procedures were performed laparoscopically. Fundoplications were performed in three different

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methods. The most used is the 180º anterior fundoplication as described by Gatenby et al.15

The laparoscopic 360º Nissen fundoplication has been described by Jamieson et al.16 The Toupet

fundoplication is a partial posterior (270º) fundoplication.17 We performed this type of fundoplication mostly

in 2013 and 2014 in a multicenter trial that compared the 180º anterior fundoplication with the Toupet

fundoplication (MANTA trial). For patients suffering achalasia we performed a laparoscopic Heller myoto-

my18, followed by a 180º anterior Dor fundoplication, as described by Rosati.19

OBJECTIVE FOLLOW-UP

Barium-swallow X-rays were performed three to six months postoperative. Objective investigations such as

24-hours-pH-metric, endoscopy, oesophageal manometry were performed postoperatively only on

indication given the invasive character.

QUESTIONNAIRES

The questionnaires included the validated Gastro-Esophageal Reflux Disease health related Quality of Life

(GERD-hr-QoL) for GERD-related quality of life20-23, and the validated QLQ-OES-24 for scoring

dysphagia.24,25 We used 10-point Visual Analogue Scales26, and asked patients to score their symptoms,

satisfaction about preoperative information, quality of care (outpatient, surgical department, ward, etc),

waiting time for the operation, postoperative care, and satisfaction after surgery. Also, we asked patients

if they would undergo the same operation again, should have undergone this operation earlier and if they

would recommend this operation to a close relative or good friend with equal symptoms, knowing what the

results are after surgery. All questionnaires were given at all time points.

FOLLOW-UP ON PAPER

Paper questionnaires were handed to the patients during their visit to the outpatient clinic before and after

surgery. The could use the prepaid envelope to return the questionnaires. When needed, patients were

reminded by telephone to complete their questionnaire. The returned questionnaires were entered in an

electronic database.

ONLINE FOLLOW-UP

Our software program (Research Manager®) is an online database in which we prospectively collect all

patient characteristics and surgical details. Patients received an automatically generated e-mail with a secured

link to the online questionnaire, on set time points, based on the date of operation. Patients were reminded

by email after seven days and more often, if needed. Patient responses are saved automatically in the online

database. Preoperative details, surgical details and clinical details are filled in by the surgeon or ward

physician. All data are exportable to an Excel or SPSS file, which makes it easy to analyze for scientific

purposes.

ANALYSES

For this study we selected all patients who underwent laparoscopic antireflux surgery in our clinic. We

compared the response rate of a cohort of patients that used paper follow-up with a cohort that used online

follow-up. Furthermore, we compared the completeness of the received questionnaires between the

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paper-collected and the online-collected data. Few patients switched from paper follow-up to online

follow-up. We performed a subanalysis with all switchers in which we compared the completeness of their

questionnaires that were done on paper to the latter, completed online. We compared baseline

characteristics and results of the questionnaires between the paper and the online group. Furthermore, we

analysed the improvement after surgery which we also compared between the paper group and the online

group.

STATISTICS

Continuous data were analysed using normalcy tests to see which data were parametrically and non-

parametrically distributed. Parametrically distributed data were analysed using Student t tests.

Non-parametric data were analysed using Mann–Whitney U tests. Categorical data were analysed using

Chi-square tests and Fisher’s exact tests ( in figure 2 and 3). Statistical analyses were performed using IBM’s

Statistical Package for Social Sciences (SPSS),version 22 for Apple Macintosh OS (IBM corp., Armonk,New

York, USA). A p value of less than 0.05 was considered to be statistically significant.

ETHICAL APPROVAL

Patients gave informed consent and were informed about the purposes of the completed questionnaires and

securely saved data. All data (both on paper and online) were coded before exported to the database. The

Institutional Review Board of our hospital has evaluated our study protocol and approved it without further

obligations.

RESULTSBASELINE CHARACTERISTICS

294 patients were included in our follow-up. Six patients were excluded (mentally incapability to fill in

questionnaires (n=2); age younger than 18 years (n=1); incapability to speak and read the Dutch language

(n=1); blindness (n=1); peroperative other diagnosis (n=1)). All patients underwent laparoscopic antireflux

surgery, for either gastro-oesophageal reflux disease (GORD, n=148), hiatal hernia oesophagei (HHO,

n=126) or achalasia (n=20). 143 patients started in the paper follow-up, 151 started in the online follow up.

151151151

151151157

151128

73

143

114

91

67

26

17

14 1

Preop: n= 294

3 months: n=271

12 months: n=219

24 months: n=140

x

xPaper follow-upOnline follow-upswitch between follow-up method

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During follow-up in time, 57 patients switched from paper to online follow-up and one patient switched from

online to paper follow-up (figure 1). Patient characteristics were equal in both groups, except for operation

type (table 1). This was mainly because the number of Toupet fundoplications was higher in the online group

due to participation in the MANTA- trial as described above.

TABLE 1. PATIENT CHARACTERISTICS

Overall (n=294) Paper (n=143) Online (n=151) P-value

Age¹ 56.3 ± 15.3 56.1 ± 17.2 56.5 ± 13.3 .831

Gender² Male 108 (36.7%) 48 (33.6%) 60 (39.7%) .279

Female 186 (63.3%) 95 (66.4%) 91 (60.3%)

Height¹ 1.71 ± 0.10 1.71 ± 0.10 1.72 ± 0.10 .244

Weight¹ 81.2 ± 13.9 80.6 ± 14.2 81.7 ± 13.7 .511

BMI¹ 27.7 ± 4.3 27.7 ± 4.6 27.6 ± 4.1 .804

Pathology² HHO 126 (42.9%) 62 (43.4%) 64 (42.7%) .726

GORD 148 (50.3%) 73 (51.0%) 74 (49.3%)

Achalasia 20 (6.8%) 8 (5.6%) 12 (7.9%)

Procedure² Anterior 180º partial 238 (81.0%) 118 (82.5%) 120 (79.5%) <0.001

Nissen 19 (6.5%) 17 (11.9%) 2 (1.3%)

Heller myotomy & Dor 20 (6.8%) 8 (5.6%) 12 (7.9%)

Toupet 17 (5.8%) 0 (0%) 17 (11.3%)

Re-operation² 13 (4.5%) 8 (5.6%) 6 (4.0%) .653

Re-operation from other clinic² 15 (5.1%) 6 (4.2%) 9 (6.0%)

BMI = Body Mass Index; HHO = Hiatal Hernia Oesophagei; GORD = Gastro-Oesophageal Reflux Disease; Data presented as either 1:mean (standard deviation), or 2:number (percentage).

RESPONSE RATE & COMPLETENESS OF DATA

Response rates of the group using online follow up were significant higher compared to the group using

follow-up on paper preoperatively, three months, one year and two years postoperatively (P<0.001

(Figure 2)). The completeness of the collected data was significant better for the online group compared to

the paper group (P<0.05 (figure 3)). 57 patients switched between follow-up method, from paper to online.

Of these patients, 36 (63.2%) responded their initial questionnaire on paper. Their next questionnaires were

filled in using the online system. Subsequently, 50 of these ‘switchers’ (87.7%) responded using the online

system. Table 2 shows that the completeness of the received data for this group had increased significant

with use of the online follow-up (77.8% on paper vs. 100% online; P=0.001). At three months postoperative

GERD-hr-QoL was lower in the paper group when compared to the online group (1.0 vs. 2.0; P=0.046).

Preoperative and at 12 and 24 months postoperative the scores were equal. OES-24 scores were

comparable in the paper and the online group. Satisfaction of surgery was better in the paper group at three

months postoperative (9.0 vs. 8.0; P=0.009), but equal at 12 and 24 months postoperative. The majority

of the patients would undergo the operation again, with the knowledge of what the effects were on their

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personal complaints. This is equal in the paper and the online group. Improvement of the GERD-hr-QoL and

OES-24 was equal in the paper group and the online group (table 3).

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%Online

Paper

24 months (n=140)12 months (n=219)3 months (n=271)Preop (n=294)

****

FIGURE 2. RESPONSE RATE* = P<0.001

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%Online

Paper

24 months (n=71)12 months (n=135)3 months (n=197)Preop (n=231)

*****

FIGURE 2. COMPLETENESS OF RECEIVED DATA* = P<0.001; ** = P<0.05

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TABLE 3. OVERALL RESULTS OF QUESTIONNAIRES

Preoperative 3 months postop 12 months postop 24 months postop

GERD-hr-QoLª 13.0 (13) ‡ 1.0 (5.0)* † 2.0 (7.0)* † ‡ 2.0 (5.8)* † ‡

OES-24ª 46.0 (14)‡ 36.0 (11.0)* † ‡ 34.0 (12.0)* † ‡ 33.0 (11.0)* † ‡

Satisfactionª - 8.0 (3.0) 8.0 (3.0)‡ 8.0 (2.3)‡

Operation againb - 175 (90.7%)‡ 119 (89.5%)‡ 66 (94.3%)‡

GERD-hr-QoL = Gastro-oesophageal reflux disease health related quality of life questionnaire. OES-24 = dysphagia questionnaire.Satisfaction = satisfaction after surgery (VAS 1-10).Operation again = number of patients that would undergo the operation again, knowing the results afterwards. Data presented as either a:median (interquartile range), or b:number (percentage).* = significant difference when compared to preoperative scores ( P<0.001)† = no difference in improvement when compared to preoperative scores between paper and online follow-up (P>0.05).‡ = equal in paper and online follow-up (P>0.05).

DISCUSSIONOnline follow-up leads to high completeness of data in this cohort following laparoscopic antireflux surgery.

This is due to higher response rates, but also due to less missing data. Patients that initially start with paper

follow-up show significant higher completeness of data when switching to online follow-up for their next

questionnaires. Patient Reported Outcome Measures (PROMs) are important to assess quality of care and

outcome of treatments.1-5,27 This can be measured with both validated questionnaires and Visual Analogue

Scales, Likert-scores or Visick-scores.26,28,29 In oncological surgery, PROMs are widely used. Registration of

outcome is common and research with PROMs in cancer patients shows that its use enhances patient-

clinician communication, patient-satisfaction and eventually quality of care.6-13,30-35 Partly due to the lack of

capacity or funding for traditional follow-up, long-term follow-up is generally not available for high-volume

elective treatments such as cholecystectomy, inguinal hernia repair, rubber band ligation of hemorrhoids

etc. Since National Health Agencies and insurance companies put more pressure on health care providers to

warrant their results of treatment, it might be interesting to report those results.14 Also, benign surgery is often

performed to improve quality of life. Therefore, PROMs, and specifically health-related quality of life

measures, are suitable for this follow-up. In the past, several methods of collecting data were used, with

different results. This varies from paper questionnaires sent by conventional mail, patient-reported diaries,

telephone interviews, clinical or home interviews and to online, web-based questionnaires.36,37 Electronic

data collection methods were used as well, and showed to be reliable and valid with good patient

participation.38-42 Follow-up after surgery for benign diseases may ask for administrative and logistic

challenges in a time with a lot of pressure on healthcare for budget cuts. Therefore inventive and efficient

methods of data collection with a low workload are needed. Russel et al found that an interactive automated

telephone system was effective for a high response rate, and analysed the sociodemographic differences

between patients that preferred different methods of data collections. In our cohort, availability of internet

or computers was not an issue, so a socio-economic bias is not probable.In this study baseline characteristics

were comparable between the ‘online’ group and the ‘offline’ group (that completed follow-up on paper),

except for the type of operation due to the multicenter MANTA-trial. Our results show higher response rates

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and completeness of received data using online follow-up. Also, a group of switching patients show

improvement in response rate and completeness of data with use of the online follow-up. This can be

explained by the automated reminders for patients that did not complete their questionnaires, but also by the

fact that it takes less effort for patients to complete their questionnaire. They can fill in the questionnaires on

their smartphone and do not need to return the questionnaires during their next visit to the outpatient clinic

nor have to bring the envelope to the mailbox. The higher response and completeness rates are also

accompanied by low efforts for researchers, due to automated e-mails and automated reminders for patients.

Since a few patients favor follow-up on paper due to difficulties using the computer and accessing the

internet, online follow-up should not be the only method offered to patients, and optional ‘offline’

follow-up on paper should still be available. Postoperative improvement of scores were not different between

the groups, which means the effects of antireflux surgery are comparable in the online and offline group.

For the lower GERD-hr-QoL score three months postoperative for the paper follow-up group we do not

have a good explanation. However, improvement of this score when compared to the preoperative score is

comparable with the online follow-up. The OES-24 was the questionnaire that was most often incomplete.

This can be explained by the length of this questionnaire: it is the section with the most questions. Antireflux

surgery has been overshadowed by bad results in the past, with poor follow-up. A strong belief that antireflux

surgery should not be recommended to patients has dominated the referral pattern in the Netherlands.43 We

chose to prospectively collect all data after antireflux surgery to provide objective and subjective high quality

data for the referring physicians and for patients. The results of this follow-up can be used to rectify these

thoughts, and restore the place of antireflux surgery as effective treatment. The patient-reported-

outcome-measures in this study can be used to adjust perioperative care and, if needed, surgical techniques,

like it has done in the past.44 It is valuable for patients to present results directly derived from other patients,

and to show the opinion of patients on success of their treatment. Instead of using

common numbers from literature, this will lead to more precise data to inform patients about outcome,

complications, PROMs and therefore patient satisfaction. The data that are collected could be used for

research purposes and health-standards, and for direct patient-care as well, since the results of the

questionnaires can be directly accessed in the database during outpatient follow-up or other patient

contacts.The results of this study could be used to stimulate health professionals to create online data-

collecting systems for follow-up of benign diseases. It could be widely used, with other options for more

accurate and complete follow-up.

In conclusion, online follow-up leads to high response rates and high completeness of data. It is a user

friendly way to collect data in large cohorts of patient with benign pathology. This data can be used to inform

patients on the surgeon or hospital results for a specific treatment. Further studies for other treatments than

antireflux surgery are warranted.

ACKNOWLEDGEMENTSThe authors thank Dr. Marco H. Blanker for his advice on the revision of this manuscript.

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26. Grant S, Aitchison T, Henderson E, Christie J, Zare S, McMurray J, et al. A comparison of the reproducibility and the sensitivity to change of visual analogue scales, Borg scales, and Likert scales in normal subjects during submaximal exercise. Chest 1999 Nov;116(5):1208-1217.27. Fitzpatrick R, Davey C, Buxton MJ, Jones DR. Evaluating patient-based outcome measures for use in clinical trials. Health Technol Assess 1998;2(14):i-iv, 1-74.28. Reips UD, Funke F. Interval-level measurement with visual analogue scales in Internet-based research: VAS Generator. Behav Res Methods 2008 Aug;40(3):699-704.29. Rijnhart-De Jong HG, Draaisma WA, Smout AJ, Broeders IA, Gooszen HG. The Visick score: a good measure for the overall effect of antireflux surgery? Scand J Gastroenterol 2008;43(7):787-793.30. Bulman CH. A ten year audit of the management of cancers of the larynx and pharynx. J Laryngol Otol 1998 Oct;112(10):948-953.31. Detmar SB, Muller MJ, Schornagel JH, Wever LD, Aaronson NK. Health-related quality-of-life assessments and patient-physician communication: a randomized controlled trial. JAMA 2002 Dec 18;288(23):3027-3034.32. Velikova G, Booth L, Smith AB, Brown PM, Lynch P, Brown JM, et al. Measuring quality of life in routine oncology practice improves communication and patient well-being: a randomized controlled trial. J Clin Oncol 2004 Feb;22(4):714-724.33. Simunovic M, Goldsmith C, Thabane L, McLeod R, Denardi F, Whelan TJ, et al. The Quality Initiative in Rectal Cancer (QIRC) trial: study protocol of a cluster randomized controlled trial in surgery. BMC Surg 2008 Feb 15;8:4-2482-8-4.34. Jakobsen E, Palshof T, Osterlind K, Pilegaard H. Data from a national lung cancer registry contributes to improve outcome and quality of surgery: Danish results. Eur J Cardiothorac Surg 2009 Feb;35(2):348-52; discussion 352.35. Campbell I, Scott N, Seneviratne S, Kollias J, Walters D, Taylor C, et al. Breast cancer characteristics and survival differences between Maori, Pacific and other New Zealand women included in the Quality Audit program of Breast Surgeons of Australia and New Zealand. Asian Pac J Cancer Prev 2015;16(6):2465-2472.36. Weinberger M, Oddone EZ, Samsa GP, Landsman PB. Are health-related quality-of-life measures affected by the mode of administration? J Clin Epidemiol 1996 Feb;49(2):135-140.37. Leidy NK, Elixhauser A, Rentz AM, Beach R, Pellock J, Schachter S, et al. Telephone validation of the Quality of Life in Epilepsy Inventory-89 (QOLIE-89). Epilepsia 1999 Jan;40(1):97-106.38. Kleinman L, Leidy NK, Crawley J, Bonomi A, Schoenfeld P. A comparative trial of paper-and-pencil versus computer administration of the Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire. Med Care 2001 Feb;39(2): 181-189.39. Bushnell DM, Martin ML, Parasuraman B. Electronic versus paper questionnaires: a further comparison in persons with asthma. J Asthma 2003;40(7):751-762.40. Marks RG. Validating electronic source data in clinical trials. Control Clin Trials 2004 Oct;25(5):437-446.41. Bushnell DM, Reilly MC, Galani C, Martin ML, Ricci JF, Patrick DL, et al. Validation of electronic data capture of the Irritable Bowel Syndrome--Quality of Life Measure, the Work Productivity and Activity Impairment Questionnaire for Irritable Bowel Syndrome and the EuroQol. Value Health 2006 Mar-Apr;9(2):98-105.42. Welker JA. Implementation of electronic data capture systems: barriers and solutions. Contemp Clin Trials 2007 May;28(3):329-336.43. Boote MC. Surgery rarely performed in reflux disease (“Zelden chirurgie bij antirefluxziekte”). Magma 2006;12(2):34-35.44. Watson DI, Jamieson GG, Devitt PG, Mitchell PC, Game PA. Paraoesophageal hiatus hernia: an important complication of laparoscopic Nissen fundoplication. Br J Surg 1995 Apr;82(4):521-523.

8Laparoscopic antireflux surgery as an effective treatment for chronic cough

Poster discussion presentation at European Respiratory Society Congress 2015, Amsterdam

Poster presentation at Chirurgendagen 2015, Veldhoven

J.H. Koetje V.B. NieuwenhuijsH.L. van WestreenenK.W. PatbergJ.W.K. van den Berg

Submitted

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ABSTRACTINTRODUCTION Previous research that describes laparoscopic antireflux surgery for chronic cough as

extra-oesophageal complaint of gastro-oesophageal reflux disease show various results.

The majority of these studies analysed patients that suffered of GORD and had

additional airway symptoms, or only describe results after total fundoplication, which

is inferior to partial fundoplication. This study describes a cohort of patients with

chronic cough as primary complaint that underwent partial fundoplication.

METHODS Patients were referred to the surgeon for chronic cough, with the suspicion that it was

caused by GORD. Patients underwent partial fundoplication. The validated Leicester

Cough Questionnaire (LCQ), cough on Visual Analogue Scale (VAS), and the vaidated

Gastro-esophageal Reflux Disease health-related Quality of Life questionnaire (GERD-

hr-QoL) were used to analyse cough and reflux related quality of life.

RESULTS 50 patients underwent laparoscopic partial fundoplication. Total LCQ scores improved

significant (10.3 preoperative versus 15.9 postoperative; P<0.001). Physical (4.0

preoperative versus 5.1 postoperative), psychological (3.7 versus 5.5), and social (3.3

versus 5.5) also demonstrated significant improvement (P<0.001). GERD-hr-QoL

showed significant improvement (10.5 versus 0.5; P<0.001) and cough symptoms

decreased significant postoperative (8.0 versus 5.0; P<0.001). Over 70% of the

patients report a high satisfaction and over 90% of the patients would undergo this

operation again with the knowledge what the results are.

CONCLUSION Laparoscopic partial fundoplication is an effective treatment for chronic cough induced

by GORD. This study could not find preoperative and perioperative parameters that

correlate with better outcome after surgery. Positive 24-hr-pH-metric and careful

history of GORD are helpful in decision making.

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Laparoscopic antireflux surgery as an effective treatment for chronic cough

8

INTRODUCTIONChronic cough can be very debilitating and can have great impact on quality of life for patients.1 It is a

common problem in both primary and secondary care. In 5-41% of the patients suffering chronic cough, it is

thought to be caused by Gastro-Oesophageal Reflux Disease (GORD).2 This specific group of patients often

has a long history of diagnoses and treatments with help from general practitioners and pulmonologists.

This so-called Gastro-Oesophageal Reflux-induced Chronic cough (GORC) is a variant of GORD, with

cough as the primary symptom.3,4 The pathophysiology is still unclear, but many hypotheses have been

proposed. There is a ‘reflux hypothesis’ which states that micro-aspiration of refluxate into the larynx and the

airways leads to atypical throat symptoms. In contrast, there is a ‘reflex hypothesis’. The latter is explained by

oesphageal-tracheobronchial reflexes that are initiated by the afferent nerves in the distal oesophagus that

are stimulated by refluxate.2,4-6 The ‘hypersensitivity syndrome’ is a more general cause of cough, in which

reflux disease could be a part.7 Also, it has been shown that typical GORD symptoms like heartburn and

regurgitation are often absent in patients demonstrating chronic cough as primary complaint. A non-acid or a

gaseous refluxate might be an explanation for these patients. Therefore GORC is often refractory to anti-acid

medication.8-10

Refractory GORD and typical GORD symptoms are established indications for antireflux surgery. Surgery

exists of laparoscopic fundoplication, which has become the treatment of choice, demonstrating good

improvement in symptoms and high patient satisfaction.11-14 Partial fundoplications (the 180° anterior and the

270° posterior (Toupet)) have shown to be superior compared to the 360° Nissen fundoplication, showing

equal reflux control and less postfundoplication symptoms like dysphagia, bloating, flatulence and inability

of belching.15-18 However, laparoscopic Nissen fundoplication could sometimes be indicated, for example in

recurrent reflux after partial fundoplication.

Several studies describe the results of antireflux surgery for cough complaints, with different outcome.10,19-26

In most studies however only patients with typical GORD symptoms as their main complaint, and additional

atypical, throat or airway symptoms were included. Three studies report good results after laparoscopic

Nissen fundoplication as treatment for cough as primary complaint.10,22,23 In addition, the use of a partial

fundoplication has not been studied before. This study describes a cohort of 50 consecutive patients who

underwent partial fundoplication for chronic cough as the main complaint. The aim of this study was to

analyse wether laparoscopic partial fundoplication was a good treatment for patients suffering chronic cough

caused by GORD. Secondary aim was to analyse which preoperative and peroperative parameters correlated

with better outcome after surgery.

METHODSPREOPERATIVE SELECTION AND WORK-UP

Patients with suspicion of chronic cough related to GORD were referred to the surgeon by the dedicated

‘cough clinic’ in our hospital. Non-GORD-related causes of chronic cough were excluded by a extensive

anatomic diagnostic protocol consisting of a metacholine challenge test, exhaled nitric oxide-fraction, and

standard bloodwork (including eosinophils), and X-ray of chest and sinus. When indicated a high-definition

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computo-tomography (HD-CT) of the thorax. GORD-related cough was also suspected when other

possible causes were not responsive to standard therapy trials. Preoperative workup included 24-hr-pH-

metry, and oesophago-gastric endoscopy. A barium swallow test, oesophageal manometry and CT-scan were

performed on indication (Table 1). If GORD as a cause of cough was doubtful, surgery was not offered to

patients.

TABLE 1. PREOPERATIVE WORKUP AND FOLLOW-UP

Diagnostics Preop Postop

Endoscopy X On indication

24-hr-pH-metry X On indication

Barium swallow On indication X

Manometry On indication On indication

Follow-up Preop Postop

Symptom scoring X X

LCQ X X

GERD-hr-Qol: X X

OES-24 X X

SF-36 X X

SURGICAL PROCEDURE

All fundoplications were performed laparoscopically. The first step is exposure of the oesophageal hiatus,

mobilisation of the oesophagus and, if needed, hiatal hernia oesophagei repair. The actual fundoplication is

performed in three different methods. The most used is the 180º anterior fundoplication (180ºLAF) as

described by Gatenby et al.27 The gastric fundus is placed loosely over the gastro-oesophageal junction at

the ventral side. Sutures through the fundus, oesophagus and hiatal cruris secure the fundoplication. The

270º posterior Toupet fundoplication (LTF) is a partial posterior fundoplication.28 The fundus is pulled

behind the oesophagus and sutures are placed through the fundus and the right and left wall of the

oesophagus at two and ten o’clock positions. Separate sutures are placed to attach the fundus to the right

hiatal pillar. The anterior oesophagus is not covered with this

procedure.

POSTOPERATIVE CARE

Patients returned to the surgical ward when they recovered from the general aneasthesia. A nasal-gastric tube

was usually not needed. Patients received standard anti-emetical medication after surgery. Oral fluids were

allowed on the day of surgery. The next day they started a soft diet. Discharge from the hospital was normally

at the second or third day postoperative. They continued the soft diet for four weeks.

FOLLOW-UP

All data were collected prospectively. Data collection started preoperatively. Patients completed different

questionnaires including Likert-scales to score cough, reflux and satisfaction, and validated questionnaires for

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cough (Leicester Cough Questionnaire (LCQ)),29 reflux (GERD-health related-Quality of Life questionnaire

(GERD-hr-QoL)), and dysphagia (OES-24). Also, patients were asked if they would undergo the operation

again. Follow-up data collection with this questionnaires was either online or on paper. Follow-up in our

outpatient clinic was at four weeks and three months after surgery with the surgeon, only when indicated

with the pulmonologist. Thereafter yearly by phone interview. At three months follow-up a routine barium

swallow X-ray was performed to document the position of the fundoplication, all other investigations were

performed on indication (Table 1).

DATA ANALYSIS

All data was collected using Research Manager, an online datacollection system witch has been described

elsewhere(ref), and the electronic patient files. Data was exported into Excel and SPSS for analysis.

Electronical hospital files were checked for further data and also used for analysis. LCQ-scores were

converted into three subdomains (physical, psychological, and social; scoring 0-7) and a total score (sum

of the three domains; scoring 0-21). Difference in preoperative and postoperative score was calculated. An

improvement in total LCQ score of 2.56 or more was considered significant.29 This value was used in further

analysis. A satisfaction of 7 or higher was considered as ‘good’.


Parametrically distributed continuous data are summarised as mean ± standard deviation (SD).

Non-parametric continuous data are summarised as median with interquartile ranges (IQR). Categorical data

are summarised as frequencies with percentages.Paired preoperative an postoperative scores were compared

using Wilcoxon Signed Rank tests. Variables were correlated with outcome postoperative to find out what

factors could influence a good result after surgery. Non-parametric data, nominal and categorical data were

tested using Spearman’s Rank correlation tests, and presented as Spearman rho correlation coefficient (rs).

Parametric data that were correlated with dichotome variables were tested using Point-biserial correlation

tests, and presented as Point-biserial correlation coefficient (rp) . A r

less than 0.40 was considered to be

weak or very weak, r of 0.40 to 0.59 to be a moderate correlation, r>0.60 to be strong, and r>0.80 to be

very strong. Correlations with r>0.35 are considered to be of clinical importance, as for these correlations the

association exceeds 10%. A P-value of <0.05 was considered statistically significant. Statistical analysis was

performed using IBM’s Statistical Package for Social Sciences (SPSS), version 22 for Apple Macintosh OS

(IBM corp., Armonk, New York, USA).

ETHICAL APPROVAL

The Institutional Research Board of our hospital approved our study without further obligations.

RESULTSBetween 2012 and 2016 we performed laparoscopic fundoplication for chronic cough as primary complaint

in 50 patients with a mean age of 57.4 years and mean body mass index (BMI) of 28.0. Mean follow-up was

26.1 months (± 10.8). The majority of the patients were female (60%, n= 30). Patient and peroperative

characteristics are shown in Table 2. A history of reflux was 86% of the patients (n=43). In 7 patients a large

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hiatal hernia (type II-IV) was present. Preoperative 24-hr-pH-metric was performed in 38 patients (76%).

Pathologic 24-hr-pH-metric was reported in 33 patients (86.8%). In 72% of patients there was an effect of

PPI (with or without a pro-kinetic drug) on complaints, but in only 34% there was a good (often temporary)

effect on cough complaints. Referall to the surgeon was mainly by a pulmonologist (76%). One patient was

directly referred from the general practitioner. 180ºLAF was performed in 42 patients (84%), 8 patients

underwent LTF. No reoperations were reported during follow-up.

TABLE 2. PATIENT AND PREOPERATIVE CHARACTERISTICS

n=50

Age1 57.4 ± 10.2

Gender2 Male 20 (40.0%)

Female 30 (60.0%)

Height1 1.72 ± 0.09

Weight1 82.9 ± 11.9

BMI1 28.0 ± 4.5

ASA-score2 1 15 (30.0%)

2 31 (62.0%)

3 4 (8.0%)

Active smoker2 4 (3.9%)

History of reflux2 43 (86.0%)

Pathology2 GORD 43 (86.0%)

HHO 7 (14.0%)

24hr-pH-metric pathologic (n=38) 2 33 (86.8%)

PPI-effect2 None 14 (28.0%)

Reflux only 19 (38.0%)

Cough 17 (34.0%)

Referred by2 Pulmonogist 38 (76.0%)

Gastro-enterologist 11 (22.0%)

Other 1 (2.0%)

Type of fundoplication2 Anterior 180º partial 42 (84.0%)

Posterior 270º partial 8 (16.0%)

Peroperative HHO2 34 (68.0%)

Reoperation2 0

BMI = Body Mass Index; ASA = American Society of Anaesthesiologists physical status classification; HHO = Hiatal Hernia Oesophagei; GORD = Gastro-Oesophageal Reflux Disease; Pathologic 24hr-pH-metric = positive when more than 4.4% of time reflux (pH<4.0); PPI-effect = effect of PPI on either cough or reflux only, or no effect; Data presented as either 1:mean ± standard deviation, or 2:number (percentage).

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Table 3 shows the results of paired pre- and postoperative scores of the LCQ the three different domains, the

GERD-hr-QoL, the OES-24, and the cough VAS. Total LCQ scores improved significant after surgery (10.3

preoperative versus 15.9 postoperative; P<0.001). Physical (4.0 preoperative versus 5.1 postoperative),

psychological (3.7 preoperative versus 5.5 postoperative), and social (3.3 preoperative versus 5.5 post-

operative) also demonstrated significant improvement (P<0.001). Cough symptoms on VAS decreased

significant postoperative (8.0 versus 5.0; P<0.001). QoL related to GORD improved significant, which was

measured with the GERD-hr-QoL that showed significant improvement following surgery (10.5 versus 0.5;

P<0.001). Dysphagia, measured with the OES24 questionnaire, showed significant improvement after

surgery (41.5 versus 35; p=0.003).

TABLE 3. PRE- AND POSTOPERATIVE SCORES OF THE LCQ, GERD-HR-QOL, OES-24, AND COUGH ON VAS

Preoperative Postoperative P-value

LCQ Total 10.3 (4.0) (n=33) 15.9 (6.53) (n=44) <0.001

Physical 4.0 (1.45) 5.1 (2.05) <0.001

Psychological 3.7 (1.55) 5.5 (2.75) 0.001

Social 3.3 (2.0) 5.3 (2.88) <0.001

GERD-hr-QoL 10.5 (10.3) (n=42) 0.5 (4.75) (n=32) <0.001

OES-24 41.5 (10.5) (n=34) 35 (7.50) (n=25) 0.003

Cough VAS 8.0 (3.0) (n=50) 5.0 (5.0) (n=46) <0.001

LCQ = Leicester Cough Questionnaire; GERD-hr-QoL = Gastro-esophageal reflux disease health related quality of life questionnaire; OES-24 = dysphagia score; Scores are compared using Related Samples Wilcoxon Signed Rank tests. Data is presented as median (interquartile range).

Table 4 shows satisfaction of surgery. Median satisfaction was 8.0 and over 70% of the patients report a high

satisfaction. More than 90% of the patients had such an clinical improvement that they would undergo this

operation again based on their current experience, after surgery.

TABLE 4. SATISFACTION OF SURGERY

n=46

Satisfaction1 8.0 (3.0)

Satisfaction > 72 33 (71.7%)

Would undergo operation again2 42 (91.3%)

Satisfaction > 7 = a score of 7 or higher for satisfaction of surgery; Data presented as either ¹:median (interquartile range), or ²:number (percentage).

Table 5 shows the correlations between the outcome scores and variables. Only ASA-score and the percent-

age of time of pH less than 4 in 24hr-pH-metric shows a correlation of clinical importance with the improve-

ment in LCQ-scores. There are also a few other significant correlations, but they do not show a correlation

coefficient > 0.35. However, sample sizes for these correlations are small.

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TABLE 5. CORRELATIONS BETWEEN OUTCOME SCORES AND DIFFERENT VARIABLES

LCQ-sign improvement (n=30)1

Cough pre- vs postop (n=46) 1

Satisfaction >7 (n=46) 1

Recommend surgery (n=46) 1

ASA .487** (.006) .304* (.040) .178 (.237) .291* (.050)

pH % time < 4 .424** (.027) .219 (.221) .186 (.300) .171 (.341)

reflux symptoms .177 (.350) -.099 (.512) .137 (.363) .299* (.044)

PPI effect on cough .154 (.416) -.110 (.466) -.048 (.749) .063 (.676)

PPI reflux and cough .100 (.599) -.252 (.091) -.043 (.776) .168 (.264)

HHO -.144 (.447) .057 (.706) .150 (.320) .099 (.514)

Data presented as correlation coefficient (P-value); * significant correlation, ** significant correlation of clinical importance1 except voor pH%, n27 for LCQ, n33 for Cough, Satisfaction, and Recommend Surgery; Spearman Rho correlations, except for Cough vs ASA, anamn reflux, PPI effect on cough, PPI effect on reflux and cough, and HHO (Point-biserial correlations)

DISCUSSION

This study presents excellent outcomes after laparoscopic antireflux surgery for patients suffering from

chronic cough based on gastro-oesophageal reflux disease. We found a significant improvement after surgery

on the Leicester Cough Questionnaires, in all three domains and for the total scores. This is also shown in

significant decrease in cough on the VAS scores. Over 90% of patients would recommend this operation to a

relative or a close friend and the satisfaction after surgery was scored 8 out of 10. These results indicate that

in carefully selected patients, laparoscopic fundoplication is a good treatment for chronic cough. Although

we describe a medium size cohort of 50 patients, it is one of the very few that describes results after antireflux

surgery as a treatment for cough as primary complaint.

Novitsky et al,22 Allen et al,23 and Faruqi et al10 have demonstrated that laparoscopic fundoplication is a

succesful treatment for patients that have cough complaints as indication for surgery. Novitsky et al describe

21 patients with cough complaints as reason for laparoscopic Nissen fundoplication. Improvement after

surgery was seen in 86% of patients. The Adverse Cough Outcome Survey (ACOS, to determine the

impact of cough on health-related disfunction) showed significant improvement (postoperative 15.1 to 5.8, 12

months after surgery). The Sickness Impact Profile score (SIP-score, to determine health-related disfunction)

improved following surgery as well (15.1 preoperative to 5.8 (6-12 weeks postoperative) to 4.2 (12 months

postoperative)). PROM’s are well documented, but follow-up is short.

Allen et al describe a large cohort of 905 patients that underwent laparoscopic Nissen fundoplication. 209

of these patients had respiratory complaints as primary reason for surgery, 173 of those patients had cough

complaints. 335 of the patients with GORD as indication for fundoplication complaint of cough. Cough

complaints in the respiratory group decreased from 10 to 3.5 after six months, 4.9 two years postoperative

and 6.1 five years after surgery. This was equal with the cough complaints in the GORD group. Unfortunately,

significance of the improvement in cough score is not presented and validated health-related questionnaires

were not used. 71% of the patients that complained of cough were improved five years after surgery (74%

after two years and 83% after six months). These numbers were not separately described for the group with

cough as primary complaint and the GORD group with concomitant cough complaints.

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Faruqi et al describe 47 patients with cough complaints as the primary indication for surgery. Improvement

after laparoscopic Nissen fundoplication was high, with decrease in VAS score for cough from 94 to 44

(P<0.001, on a 0-100 scale). The Hull Airway Reflux Questionnaire (HARQ) showed significant

improvement after surgery.

Our study shows comparable outcome with these three previous studies. One major difference is the type

of fundoplication. All studies describe results of 360º Nissen fundoplication, whilst we describe results after

partial fundoplication, which has become standard treatment, with equal reflux control and patient

satisfaction, but less post-fundoplication symptoms like bloating or dysphagia.17,30-32

Previous studies could not distinguish the patient and/or surgical characteristics that were predictive for

good result after surgery, but suggested that 24-hr-pH-metric is important to prove presence of GORD. In

our study, correlation subanalyses showed correlations of clinical importance for ASA-score and the 24hr-

pH-metric only. Unfortunately, the groups used in these correlations were small, with sizes of 27 and 30

patients. It is too early to conclude that only these two variables are of clinical importance. A history of reflux,

the effect of PPI on cough and/or reflux, and the presence of a HHO might prove to be relevant as well. This

should be analysed in the future with a larger cohort.

Our suggestion is, based on our experience in this study and data presented in previous studies, that a 24-hr-

pH-metric test during a period without use of proton-pump-inhibitors or other anti-GORD medication

should be performed in all patients that are candidate for laparoscopic fundoplication with chronic cough as

reason for surgery. Although it shows an important correlation, a positive 24-hr-pH-metric should not always

be guiding in shared decision making. Some patients suffer chronic cough for many years with great impact

on quality of life and are desperate for a treatment. If 24-hr-pH-metric is negative, but history is suggestive

for cough based on GORD, fundoplication may be helpful. But there is a risk of non-response. That should

be carefully discussed with patients. Other ways of functional assessment of oesophageal motility could be

helpful, but need further validation and were not performed routinely in this cohort.

In conclusion, this study shows good results of laparoscopic partial fundoplication as a treatment for chronic

cough induced by GORD. It promises to find the preoperative and perioperative parameters that correlate

with better outcome after surgery, and thus how to select the right patients with chronic cough for antireflux

surgery in the future. Positive 24-hr-pH-metric and careful history of GORD are helpful in decision making.

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REFERENCES

1. Chamberlain SA, Garrod R, Douiri A, et al. The impact of chronic cough: A cross-sectional european survey. Lung. 2015;193(3):401-408.2. Morice AH, Kastelik JA. Cough. 1: Chronic cough in adults. Thorax. 2003;58(10):901-907.3. Irwin RS. Chronic cough due to gastroesophageal reflux disease: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 Suppl):80S-94S.4. Blondeau K, Dupont LJ, Mertens V, Tack J, Sifrim D. Improved diagnosis of gastro-oesophageal reflux in patients with unexplained chronic cough. Aliment Pharmacol Ther. 2007;25(6):723-732.5. Scott DR, Simon RA. Supraesophageal reflux disease: A review of the literature. Allergy Asthma Proc. 2014;35(2):104-110.6. Lv HJ, Qiu ZM. Refractory chronic cough due to gastroesophageal reflux: Definition, mechanism and management. World J Methodol. 2015;5(3):149-156.7. Morice AH, Millqvist E, Belvisi MG, et al. Expert opinion on the cough hypersensitivity syndrome in respiratory medicine. Eur Respir J. 2014;44(5):1132-1148.8. Faruqi S, Molyneux ID, Fathi H, Wright C, Thompson R, Morice AH. Chronic cough and esomeprazole: A double-blind placebo-controlled parallel study. Respirology. 2011;16(7):1150-1156.9. Waring JP, Lacayo L, Hunter J, Katz E, Suwak B. Chronic cough and hoarseness in patients with severe gastroesophageal reflux disease. diagnosis and response to therapy. Dig Dis Sci. 1995;40(5):1093-1097.10. Faruqi S, Sedman P, Jackson W, Molyneux I, Morice AH. Fundoplication in chronic intractable cough. Cough. 2012;8(1):3- 9974-8-3.11. Broeders JA, Bredenoord AJ, Hazebroek EJ, Broeders IA, Gooszen HG, Smout AJ. Effects of anti-reflux surgery on weakly acidic reflux and belching. Gut. 2011;60(4):435-441.12. Galmiche JP, Hatlebakk J, Attwood S, et al. Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: The LOTUS randomized clinical trial. JAMA. 2011;305(19):1969-1977.13. Grant AM, Cotton SC, Boachie C, et al. Minimal access surgery compared with medical management for gastro- oesophageal reflux disease: Five year follow-up of a randomised controlled trial (REFLUX). BMJ. 2013;346:f1908.14. Schijven MP, Gisbertz SS, van Berge Henegouwen MI. Laparoscopic surgery for gastro-esophageal acid reflux disease. Best Pract Res Clin Gastroenterol. 2014;28(1):97-109.15. Baigrie RJ, Cullis SN, Ndhluni AJ, Cariem A. Randomized double-blind trial of laparoscopic nissen fundoplication versus anterior partial fundoplication. Br J Surg. 2005;92(7):819-823.16. Ludemann R, Watson DI, Jamieson GG, Game PA, Devitt PG. Five-year follow-up of a randomized clinical trial of laparoscopic total versus anterior 180 degrees fundoplication. Br J Surg. 2005;92(2):240-243.17. Broeders JA, Mauritz FA, Ahmed Ali U, et al. Systematic review and meta-analysis of laparoscopic nissen (posterior total) versus toupet (posterior partial) fundoplication for gastro-oesophageal reflux disease. Br J Surg. 2010;97(9):1318-1330.18. Koch OO, Kaindlstorfer A, Antoniou SA, Asche KU, Granderath FA, Pointner R. Laparoscopic nissen versus toupet fundoplication: Objective and subjective results of a prospective randomized trial. Surg Endosc. 2012;26(2):413-422.19. Johnson WE, Hagen JA, DeMeester TR, et al. Outcome of respiratory symptoms after antireflux surgery on patients with gastroesophageal reflux disease. Arch Surg. 1996;131(5):489-492.20. Chen RY, Thomas RJ. Results of laparoscopic fundoplication where atypical symptoms coexist with oesophageal reflux. Aust N Z J Surg. 2000;70(12):840-842.21. Farrell TM, Richardson WS, Trus TL, Smith CD, Hunter JG. Response of atypical symptoms of gastro-oesophageal reflux to antireflux surgery. Br J Surg. 2001;88(12):1649-1652.22. Novitsky YW, Zawacki JK, Irwin RS, French CT, Hussey VM, Callery MP. Chronic cough due to gastroesophageal reflux disease: Efficacy of antireflux surgery. Surg Endosc. 2002;16(4):567-571.23. Allen CJ, Anvari M. Does laparoscopic fundoplication provide long-term control of gastroesophageal reflux related cough? Surg Endosc. 2004;18(4):633-637.24. Kaufman JA, Houghland JE, Quiroga E, Cahill M, Pellegrini CA, Oelschlager BK. Long-term outcomes of laparoscopic antireflux surgery for gastroesophageal reflux disease (GERD)-related airway disorder. Surg Endosc. 2006;20(12): 1824-1830.25. Brown SR, Gyawali CP, Melman L, et al. Clinical outcomes of atypical extra-esophageal reflux symptoms following laparoscopic antireflux surgery. Surg Endosc. 2011;25(12):3852-3858.26. Ratnasingam D, Irvine T, Thompson SK, Watson DI. Laparoscopic antireflux surgery in patients with throat symptoms: A word of caution. World J Surg. 2011;35(2):342-348.27. Gatenby PA, Bright T, Watson DI. Anterior 180 degrees partial fundoplication--how I do it. J Gastrointest Surg. 2012;16(12): 2297-2303.28. Toupet A. Technic of esophago-gastroplasty with phrenogastropexy used in radical treatment of hiatal hernias as a supplement to heller’s operation in cardiospasms. Mem Acad Chir (Paris). 1963;89:384-389.

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29. Birring SS, Prudon B, Carr AJ, Singh SJ, Morgan MD, Pavord ID. Development of a symptom specific health status measure for patients with chronic cough: Leicester cough questionnaire (LCQ). Thorax. 2003;58(4):339-343.30. Stefanidis D, Hope WW, Kohn GP, et al. Guidelines for surgical treatment of gastroesophageal reflux disease. Surg Endosc. 2010;24(11):2647-2669.31. Broeders JA, Roks DJ, Ahmed Ali U, Draaisma WA, Smout AJ, Hazebroek EJ. Laparoscopic anterior versus posterior fundoplication for gastroesophageal reflux disease: Systematic review and meta-analysis of randomized clinical trials. Ann Surg. 2011;254(1):39-47.32. Broeders JA, Roks DJ, Ali UA, et al. Laparoscopic anterior 180-degree versus nissen fundoplication for gastroesophageal reflux disease: Systematic review and meta-analysis of randomized clinical trials. Ann Surg. 2013;257(5):850-859.

9 Summary,General discussion, andFinal conclusions

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Summary, general discussion, and final conclusions

9

GENERAL DISCUSSION

The studies in this thesis focus on the follow-up and results of laparoscopic antireflux surgery. In this chapter

these studies will be summarised by answering the questions that were drafted in CHAPTER 1.

WHAT IS THE BEST FUNDOPLICATION?

Laparoscopic antireflux surgery (LARS) in the form of laparoscopic fundoplication has proven itself as an

effective therapy for gastro-oesophageal reflux disease (GORD).1-8 It has become standard treatment for

patients who do not respond to medical therapy with acid suppression, together with patients that suffer

non-acid reflux, have extra-oesophageal complaints of GORD, and the patients who are not willing to take

lifelong medication.9-12 Partial fundoplications, like the laparoscopic 270º posterior Toupet fundoplication

(LTF) and the laparoscopic 180º anterior fundoplication (180ºLAF) demonstrated equal reflux control

compared to laparoscopic 360º Nissen fundoplication (LNF), but less dysphagia and other post-

fundoplication symptoms in a number of randomised trials13-25 and reviews.26-29 Whether the 180ºLAF or

the LTF is best fundoplication remained unclear.27,30 A recent randomised clinical trial aimed to compare

180ºLAF and LTF but failed to include enough patients.31 In CHAPTER 2 the short-term results of a

randomised clinical trial that evaluated the 180ºLAF and the LTF are demonstrated. This randomised

controlled trial is the first trial with sufficient sample size that compares 180ºLAF and LTF directly. Both

procedures provide similar reflux control, postfundoplication symptoms, and patient satisfaction. This is

comparable with the underpowered results of the previous mentioned trial. A new finding was that increased

flatulence and chest pain occurred more frequently after LTF. This might be a negative side effect of the LTF.

LOS residual resting pressure was lower in the LTF group, but it is uncertain whether this is of clinical

importance. Patient reported outcome measures (PROM’s), measured by Dakak dysphagia score and

satisfaction and symptoms scores using visual analogue scales, were equal after both procedures: patients

were highly satisfied and reported a significant reduction in symptoms. Dysphagia score was the primary

outcome. These were equal in the two groups. However, two patients needed reoperation for acute

dysphagia following LTF as initial operation. After conversion to 180ºLAF, outcome was good as reported

by the patients, demonstrating no dysphagia and effective reflux control. Operation video analysis did not

find explanations for perioperative errors, and per protocol analysis showed no difference in outcome due

to these crossover patients. Despite the lack of significant difference between 180ºLAF and LTF, this acute

dyspagia in the LTF group might be important and needs to be addressed in future research in to exclude

coincidence. Short-term results are not enough to conclude that both procedures lead to similar outcome.

Long-term results of this trial need to be awaited and further research with larger cohorts might find clinical

significant differences between the 180ºLAF and LTF. A preliminary conclusion is that the 180ºLAF and the

LTF tied for first place in treatment for GORD and that the surgeon’s expertise should decide which

procedure is best suitable for the individual patient.

IS LAPAROSCOPIC HIATAL HERNIA REPAIR WITH AND WITHOUT MESH SAFE AND EFFECTIVE?

Laparoscopic hiatal hernia repair, performed by dissection of the hernial sac from the mediastinum into the

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abdomen, followed by cruroplasty with sutures and additional fundoplication,32-34 is the standard treatment

for symptomatic hiatal hernia type II-IV35 Due to high recurrence rates use of mesh has gained popularity,

aiming to reduce these recurrence rates. Randomised controlled trials from 200236 and 200537 reported

lower recurrence rate with use of mesh. The first paper even reported 0% recurrence rate at short-term

follow-up after use of key-hole mesh (which is associated with more mesh-related complications compared

to use of U-shaped mesh for reinforcement at posterior crura).38-40 But no long-term follow-up was

published and use of mesh was associated with higher incidence of postoperative dysphagia. In 2011

long-term results of a randomised controlled trial were demonstrated equal recurrence and complication

rates with or without use of a biologic mesh,41 whereas on short-term use of mesh provided significant less

recurrence rates.42 A number of several prospective and retrospective studies demonstrated varying

results.43-49 Although mesh can lead to serious complications,39,40,50,51 two recent meta-analyses concluded

a possible favorable outcome for use of mesh in recurrence rate, but not for reoperation rate.52,53 Only few

studies used PROM’s as outcome.41,44,46,54 CHAPTER 3 and CHAPTER 4 demonstrate that use of mesh in

laparoscopic large hiatal hernia repair does not influence radiologic or symptomatic recurrence rate, and has

equal numbers of reoperation. Quality of life (QoL) and dysphagia improve significant after surgery, and are

equal between primary cruraplasty and use of either absorbable or non-absorbable mesh.

In CHAPTER 3 the reported patient satisfaction is high and no mesh-related complications were seen in a

large cohort of consecutive patients. Although the study is a non-randomised cohort analysis, it describes the

largest retrospective cohort of prospective followed consecutive patients. Results are comparable with the

previously published randomised controlled trials that provide long-term follow-up. It uses PROM’s as

outcome, which is important to provide a perspective that might be more relevant to the individual patient,

compared to objective outcome measurements.55 This will be discussed later in this chapter.

In CHAPTER 4 the PROM’s of a randomised controlled trial that compares primary cruraplasty,

absorbable bio-mesh, and non-absorbable prosthetic mesh are described. Like the objective outcome that

was reported previously,54 the QoL is comparable between the three different techniques. All procedures

provide improvement of QoL. Primary outcome of this trial was recurrence rate, which was equal in all three

groups. In a subanalysis, patient with recurrent hiatal hernia demonstrated lower QoL compared to patients

without recurrence. However, patients with symptomatic recurrence report reduced QoL compared to

asymptomatic recurrent and non-recurrent hiatal hernia. Asymptomatic recurrence rate should therefore

not be used as outcome measure for studies that evaluate use of mesh in hiatal hernia repair. As a criterion

to consider reoperation symptomatic recurrence (that is confirmed with objective investigations) should be

used. This demonstrates the benefit of reporting the PROM’s and reporting both the symptomatic and

asymptomatic recurrence rates.

Although increased age is associated with higher morbidity during surgery, our study that is described in

CHAPTER 5 concludes that laparoscopic hiatal hernia repair is save in the elderly patient. Other studies

report different results, but also describe very heterogeneous groups with more primary open procedures,

more conversions to laparotomy, longer operation time, and higher ASA-scores.56-60 A number of patients in

those studies underwent surgery in hospitals that had only little experience with laparoscopic hiatal hernia

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repair. In our cohort, surgeons that are specialised in LARS and hiatal hernia correction performed all the

procedures. A bias might be a possible pre-selection that was done by referring physicians that did not refer

the most morbidly patients. The use of mesh did not demonstrate serious complications in the studies

addressed in the previous chapters, but it has been reported previously. In order to avoid these

complications, in conjunction with the results reported in chapter 3, 4 and 5, and the five-year follow-up of

a RCT,41 use of mesh in primary large hiatal hernia correction should be discouraged. Long-term follow-up of

multiple trials using different types of mesh and different placement techniques might change this

perspective. In conclusion, laparoscopic hiatal hernia repair is effective without the use of mesh. Performing

laparoscopic hiatal hernia repair in the elderly patient is safe.

WHAT IS THE APPROPRIATE METHOD OF FOLLOW-UP FOR PATIENTS FOLLOWING

LAPAROSCOPIC ANTIREFLUX SURGERY?

Many studies that evaluate LARS focus on objective outcome measurements. However, since GORD and

hiatal hernia impair QoL, using the QoL as outcome seems to appropriate.55,61,62 Since QoL and other

PROM’s provide a better reflection of the results after surgery for the individual patient, these outcomes

might be more relevant.55,61,63 General measures of satisfaction as the Likert satisfaction scale or Visual

Analogue Scales, and general QoL assessments with the SF-36 were used in heaps of studies reporting on

LARS.63-65 In CHAPTER 6, however, the use of the SF-36 for follow-up of LARS is discouraged, since

clinically significant correlations between the SF-36 and reflux symptoms were not identified in large cohort

of 329 consecutive patients. Correlation of the SF-36 component scores with satisfaction showed weak

correlation at three months follow-up, but no correlation at longer-term follow-up as well. The health-related

questionnaire that was used in this study (the GERD-hr-QoL) demonstrates high correlation with the

postoperative symptom scores and the patient satisfaction and should therefore be used in future research to

assess QoL after LARS. Although preoperative correlations were weak, the postoperative correlations were

very strong. The SF-36 reflects many generic issues and is not specific enough to assess results of LARS. In

an earlier study the SF-36 and the GERD-hr-QoL were also compared to evaluate whether the outcomes

were useful in LARS. However, this study only used a small cohort of patients, only evaluated outcome at

one follow-up moment, and did not perform direct correlations between the validated questionnaires and

reflux symptoms and patient satisfaction. Since there is not agreed upon a standard measure for follow-up of

LARS, the results of the study in chapter 6 could not be compared with a “gold standard”. Likert scores and

Visual Analoque Scales that were correlated with the SF-36 and the GERD-hr-QoL in this study have

previously shown a good correlation with clinically important outcome following LARS, as well as with

objective measurements, such as 24-hour oesophageal pH test.66-68

To obtain PROM’s it is important that as many patients as possible are included in follow-up. Complete data

is important in research, but for validated questionnaires complete data is often essential to present reliable

and grounded results. CHAPTER 7 presents the significant higher response rates and completeness rates

with the use of an online data collection system that automatically sends questionnaires per e-mail on pre-

planned moments, compared to the old-fashioned paper based questionnaires that were send by post.

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Privacy needs to be warranted, but with use of secure servers, online data collection is an effective method

for collection of PROM’s, which takes little effort for researchers and patients.

In the past, antireflux surgery had a bad reputation in the Netherlands. In particular because of high

complication rates after surgery, which was thought to be due to limited experience of the surgeons who

carried out this antireflux surgery. Recently, conceptual guidelines are drafted to set volume standards for

LARS. The implementation of a national, online database for all patients that undergo LARS in the

Netherlands is under consideration. Combining the follow-up data in a shared database using the same

PROM’s would lead to a large database that could provide accurate information about the results of LARS.

The online data collection system that is described in chapter 7 is analysed for follow-up after LARS, but

could be implemented for all types of (benign) surgery. Since benign surgery is often performed to

improve QoL, it seems relevant to evaluate this QoL after surgery. Lacking capacity and funding in the

current health-care system, the follow-up of high-volume elective surgery is generally unavailable. Follow-up

usually comprises a single visit to the outpatient clinic or evaluation by phone after surgery, to ensure that no

complications have occurred. But the use of an online system could provide a simple mechanism for

collection of many data including PROM’s. It could help to develop quality control systems and provide

patients with accurate information (supplied by other patients) regarding hospital- or surgeon-specific results

per treatment. Physicians could use these data to evaluate their treatments. They could provide National

health agencies and insurance companies (that put more pressure on health care providers to warrant their

results) with reliable outcome after surgery, reported by patients. Thus, PROM’s should be used for

follow-up of laparoscopic antireflux surgery, preferably using health-related quality of life questionnaires and

symptom scores. Objective outcome is important, but symptomatic outcomes, reported by patients, should

be used to evaluate LARS. Online follow-up is a highly effective and easy method for collection of PROM’s.

It should be implemented as standard follow-up for all patients that undergo LARS to easily collect a large

amount of valuable data.

DO PATIENTS SUFFERING FROM CHRONIC COUGH BENEFIT FROM LAPAROSCOPIC

ANTIREFLUX SURGERY?

Several studies describe the results of antireflux surgery for cough complaints, but most studies actually

describe a cohort of patients with typical GORD symptoms as their main complaint, and additional atypical,

throat or airway symptoms. Various outcomes are reported.69-77 Only three studies describe good results

after laparoscopic Nissen fundoplication as treatment for cough as primary complaint,72,73,77 but use of a

partial fundoplication was not described. CHAPTER 8 presents the outcomes after laparoscopic antireflux

surgery for patients suffering from this so-called gastro-oesophageal reflux induced chronic cough (GORC)

as primary complaint. There is a significant improvement after surgery on the validated Leicester Cough

Questionnaires, in all three domains and for the total scores. Also cough symptoms on a VAS decrease

significant, GERD-hr-QoL improves significant and patient satisfaction was high following LARS. Although

this study was performed in a medium size, non-randomised cohort of 50 patients, it is one of the few studies

that describe results after antireflux surgery as a treatment for cough as primary complaint. It is the first study

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that describes these results after partial fundoplication for chronic cough. Previous studies could not

distinguish the patient and/or surgical characteristics that predict a good result after surgery, but suggested

that 24-hour opesophageal pH test is important to prove presence of GORD. In our study, the groups that

were used for correlation analyses were small, and therefore results of this correlation are not representative.

Our suggestion, based on our experience in this study and data presented in previous studies, is that a 24-

hour opesophageal pH test during a period without use of proton-pump-inhibitors (PPI’s) or other anti-

GORD medication should be performed in all patients that are candidate for laparoscopic fundoplication

with chronic cough as reason for surgery. If 24-hour opesophageal pH test is negative, but a patient’s history

is suggestive for cough based on GORD, fundoplication may be helpful, but the risk of non-response should

be carefully discussed. The effect of PPI on cough and/or reflux, and the presence of a hiatal hernia might be

relevant as well. This should be analysed in the future with a larger cohort. Conclusion of this study is that

laparoscopic antireflux surgery is an effective treatment for carefully selected patients suffering chronic cough

caused by GORD.

IMPLICATIONS FOR THE CURRENT CLINICAL PRACTICE

The conclusions that were drafted in this thesis can be translated to the clinical practice as follows:

•• Laparoscopic 180º anterior fundoplication and laparoscopic 270º Toupet fundoplication should

be used as preferred surgical treatment for LARS. The expertise of the surgeon should decide

which partial fundoplication to perform, until long-term results of the MANTA-trial are available.

•• Use of mesh in laparoscopic hiatal hernia repair does not lead to a reduced rate of symptomatic

recurrence or reoperation. Mesh can cause serious complications. Therefore, mesh should not be

routinely used in hiatal hernia repair.

•• Symptomatic recurrence rates measured with PROM’s should be used in studies that report on

hiatal hernia repair. Radiologic, or asymptomatic recurrence is not a good outcome measurement.

•• Laparoscopic antireflux surgery should be considered as a treatment for patients suffering from

gastro-oesophageal reflux induced chronic cough.

•• Patient reported outcome measures with validated health-related quality of life questionnaires,

symptom scores and patient satisfaction scores, should be used for follow-up of laparoscopic

antireflux surgery.

•• A shared, national online data collection system that uses PROM’s should be implemented for all

patients that undergo laparoscopic antireflux surgery in The Netherlands.

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SUGGESTIONS FOR FUTURE RESEARCH

The studies that are addressed in this thesis do not provide definitive answers to all research objectives.

Future research is needed to gain more knowledge and certainty to provide funded advices for the clinical

practice. The four questions that were drafted in the introduction are shortly discussed below with advices

for future research.

What is the best fundoplication?

The long-term results of the MANTA-trial should provide the answer to this question.

Is hiatal hernia repair with and without mesh safe and effective?

A double-blind randomised clinical trial that compares primary cruraplasty with cruraplasty reinforced with

mesh, powered for symptomatic recurrence could answer this question. Outcome should be measured in

PROM’s using health-related quality of life questionnaires and symptom scores. Objective investigations,

with barium swallow X-rays, should be performed to confirm hiatal hernia recurrence in symptomatic

patients.

What is the appropriate method of follow-up for patients following laparoscopic antireflux surgery?

Future research should use PROM’s with health-related quality of life questionnaires, symptom scores and

patient satisfaction scores, and avoid generic quality of life questionnaires. If large randomised studies that

compare different laparoscopic antireflux surgery procedures would implement this PROM’s together with

objective investigations, these symptomatic quality of life measurements could be correlated with symptom

scores and objective measurements. Larger cohorts will provide more accurate results. In addition, a

randomised trial that includes patients in either online follow-up or paper follow-up would strengthen the

results of the study addressed in chapter 7.

Do patients suffering from chronic cough benefit from laparoscopic antireflux surgery?

The study in chapter 8 answers this question, but a larger cohort may confirm the results. Long-term

follow-up needs to be awaited. A trial that compares laparoscopic antireflux surgery and conservative

treatment using medications (including protonpump inhibitors) might consolidate our conclusion that anti-

reflux surgery is beneficial for selected patients with gastro-oesophageal reflux induced chronic cough. In a

larger cohort, univariate and multivariate analyses could demonstrate predictive factors for good outcome

after laparoscopic antireflux surgery for patients with chronic cough. This could ease the selection of patients

that are expected to show a good postoperative result.

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REFERENCES 1. Ireland AC, Holloway RH, Toouli J, Dent J. Mechanisms underlying the antireflux action of fundoplication. Gut 1993 Mar;34(3):303-308.2. Watson DI, Jamieson GG. Antireflux surgery in the laparoscopic era. Br J Surg 1998 Sep;85(9):1173-1184.3. Lundell L, Miettinen P, Myrvold HE, Pedersen SA, Liedman B, Hatlebakk JG, et al. Continued (5-year) followup of a randomized clinical study comparing antireflux surgery and omeprazole in gastroesophageal reflux disease. J Am Coll Surg 2001 Feb;192(2):172-9; discussion 179-81.4. Watson DI. Laparoscopic treatment of gastro-oesophageal reflux disease. Best Pract Res Clin Gastroenterol 2004 Feb;18(1):19-35.5. Engstrom C, Cai W, Irvine T, Devitt PG, Thompson SK, Game PA, et al. Twenty years of experience with laparoscopic antireflux surgery. Br J Surg 2012 Oct;99(10):1415-1421.6. Grant AM, Cotton SC, Boachie C, Ramsay CR, Krukowski ZH, Heading RC, et al. Minimal access surgery compared with medical management for gastro-oesophageal reflux disease: five year follow-up of a randomised controlled trial (REFLUX). BMJ 2013 Apr 18;346:f1908.7. Schijven MP, Gisbertz SS, van Berge Henegouwen MI. Laparoscopic surgery for gastro-esophageal acid reflux disease. Best Pract Res Clin Gastroenterol 2014 Feb;28(1):97-109.8. Hatlebakk JG, Zerbib F, Bruley des Varannes S, Attwood SE, Ell C, Fiocca R, et al. Gastroesophageal Acid Reflux Control 5 Years After Antireflux Surgery, Compared With Long-term Esomeprazole Therapy. Clin Gastroenterol Hepatol 2016 May;14(5):678-685.e3.9. Fass R. Proton pump inhibitor failure--what are the therapeutic options? Am J Gastroenterol 2009 Mar;104 Suppl 2: S33-8.10. Broeders JA, Rijnhart-de Jong HG, Draaisma WA, Bredenoord AJ, Smout AJ, Gooszen HG. Ten-year outcome of laparoscopic and conventional nissen fundoplication: randomized clinical trial. Ann Surg 2009 Nov;250(5):698-706.11. Fass R. Therapeutic options for refractory gastroesophageal reflux disease. J Gastroenterol Hepatol 2012 Apr;27 Suppl 3:3-7.12. Sifrim D, Zerbib F. Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors. Gut 2012 Sep;61(9):1340-1354.13. Hagedorn C, Lonroth H, Rydberg L, Ruth M, Lundell L. Long-term efficacy of total (Nissen-Rossetti) and posterior partial (Toupet) fundoplication: results of a randomized clinical trial. J Gastrointest Surg 2002 Jul-Aug;6(4):540-545.14. Zornig C, Strate U, Fibbe C, Emmermann A, Layer P. Nissen vs Toupet laparoscopic fundoplication. Surg Endosc 2002 May;16(5):758-766.15. Baigrie RJ, Cullis SN, Ndhluni AJ, Cariem A. Randomized double-blind trial of laparoscopic Nissen fundoplication versus anterior partial fundoplication. Br J Surg 2005 Jul;92(7):819-823.16. Ludemann R, Watson DI, Jamieson GG, Game PA, Devitt PG. 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Laparoscopic fundoplication: Nissen versus Toupet two-year outcome of a prospective randomized study of 200 patients regarding preoperative esophageal motility. Surg Endosc 2008 Jan;22(1):21-30.21. Shaw JM, Bornman PC, Callanan MD, Beckingham IJ, Metz DC. Long-term outcome of laparoscopic Nissen and laparoscopic Toupet fundoplication for gastroesophageal reflux disease: a prospective, randomized trial. Surg Endosc 2010 Apr;24(4):924-932.22. Mardani J, Lundell L, Engstrom C. Total or posterior partial fundoplication in the treatment of GERD: results of a randomized trial after 2 decades of follow-up. Ann Surg 2011 May;253(5):875-878.23. Raue W, Ordemann J, Jacobi CA, Menenakos C, Buchholz A, Hartmann J. Nissen versus Dor fundoplication for treatment of gastroesophageal reflux disease: a blinded randomized clinical trial. Dig Surg 2011;28(1):80-86.24. Koch OO, Kaindlstorfer A, Antoniou SA, Asche KU, Granderath FA, Pointner R. 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Stadlhuber RJ, Sherif AE, Mittal SK, Fitzgibbons RJ,Jr, Michael Brunt L, Hunter JG, et al. Mesh complications after prosthetic reinforcement of hiatal closure: a 28-case series. Surg Endosc 2009 Jun;23(6):1219-1226.40. Frantzides CT, Carlson MA, Loizides S, Papafili A, Luu M, Roberts J, et al. Hiatal hernia repair with mesh: a survey of SAGES members. Surg Endosc 2010 May;24(5):1017-1024.41. Oelschlager BK, Pellegrini CA, Hunter JG, Brunt ML, Soper NJ, Sheppard BC, et al. Biologic prosthesis to prevent recurrence after laparoscopic paraesophageal hernia repair: long-term follow-up from a multicenter, prospective, randomized trial. J Am Coll Surg 2011 Oct;213(4):461-468.42. Oelschlager BK, Pellegrini CA, Hunter J, Soper N, Brunt M, Sheppard B, et al. Biologic prosthesis reduces recurrence after laparoscopic paraesophageal hernia repair: a multicenter, prospective, randomized trial. Ann Surg 2006 Oct;244(4): 481-490.43. Carlson MA, Richards CG, Frantzides CT. Laparoscopic prosthetic reinforcement of hiatal herniorrhaphy. Dig Surg 1999;16(5):407-410.44. Morino M, Giaccone C, Pellegrino L, Rebecchi F. Laparoscopic management of giant hiatal hernia: factors influencing long- term outcome. Surg Endosc 2006 Jul;20(7):1011-1016.45. Muller-Stich BP, Holzinger F, Kapp T, Klaiber C. Laparoscopic hiatal hernia repair: long-term outcome with the focus on the influence of mesh reinforcement. Surg Endosc 2006 Mar;20(3):380-384.46. Soricelli E, Basso N, Genco A, Cipriano M. Long-term results of hiatal hernia mesh repair and antireflux laparoscopic surgery. Surg Endosc 2009 Nov;23(11):2499-2504.47. Braghetto I, Korn O, Csendes A, Burdiles P, Valladares H, Brunet L. Postoperative results after laparoscopic approach for treatment of large hiatal hernias: is mesh always needed? Is the addition of an antireflux procedure necessary? Int Surg 2010 Jan-Mar;95(1):80-87.48. Dallemagne B, Kohnen L, Perretta S, Weerts J, Markiewicz S, Jehaes C. Laparoscopic repair of paraesophageal hernia. Long- term follow-up reveals good clinical outcome despite high radiological recurrence rate. Ann Surg 2011 Feb;253(2): 291-296.49. Gouvas N, Tsiaoussis J, Athanasakis E, Zervakis N, Pechlivanides G, Xynos E. Simple suture or prosthesis hiatal closure in laparoscopic repair of paraesophageal hernia: a retrospective cohort study. Dis Esophagus 2011 Feb;24(2):69-78.50. Tatum RP, Shalhub S, Oelschlager BK, Pellegrini CA. Complications of PTFE mesh at the diaphragmatic hiatus. J Gastrointest Surg 2008 May;12(5):953-957.

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51. Hazebroek EJ, Leibman S, Smith GS. Erosion of a composite PTFE/ePTFE mesh after hiatal hernia repair. Surg Laparosc Endosc Percutan Tech 2009 Apr;19(2):175-177.52. Memon MA, Memon B, Yunus RM, Khan S. Suture Cruroplasty Versus Prosthetic Hiatal Herniorrhaphy for Large Hiatal Hernia: A Meta-analysis and Systematic Review of Randomized Controlled Trials. Ann Surg 2016 Feb;263(2):258-266.53. Tam V, Winger DG, Nason KS. A systematic review and meta-analysis of mesh vs suture cruroplasty in laparoscopic large hiatal hernia rrepair. Am J Surg 2016 Jan;211(1):226-238.54. Watson DI, Thompson SK, Devitt PG, Smith L, Woods SD, Aly A, et al. Laparoscopic repair of very large hiatus hernia with sutures versus absorbable mesh versus nonabsorbable mesh: a randomized controlled trial. Ann Surg 2015 Feb;261(2):282-289.55. Kamolz T, Granderath F, Pointner R. Laparoscopic antireflux surgery: disease-related quality of life assessment before and after surgery in GERD patients with and without Barrett’s esophagus. Surg Endosc 2003 Jun;17(6):880-885.56. Gangopadhyay N, Perrone JM, Soper NJ, Matthews BD, Eagon JC, Klingensmith ME, et al. Outcomes of laparoscopic paraesophageal hernia repair in elderly and high-risk patients. Surgery 2006 Oct;140(4):491-8; discussion 498-9.57. Poulose BK, Gosen C, Marks JM, Khaitan L, Rosen MJ, Onders RP, et al. Inpatient mortality analysis of paraesophageal hernia repair in octogenarians. J Gastrointest Surg 2008 Nov;12(11):1888-1892.58. Larusson HJ, Zingg U, Hahnloser D, Delport K, Seifert B, Oertli D. Predictive factors for morbidity and mortality in patients undergoing laparoscopic paraesophageal hernia repair: age, ASA score and operation type influence morbidity. World J Surg 2009 May;33(5):980-985.59. Oelschlager BK, Petersen RP, Brunt LM, Soper NJ, Sheppard BC, Mitsumori L, et al. Laparoscopic paraesophageal hernia repair: defining long-term clinical and anatomic outcomes. J Gastrointest Surg 2012 Mar;16(3):453-459.60. Molena D, Mungo B, Stem M, Feinberg RL, Lidor AO. Outcomes of operations for benign foregut disease in elderly pa tients: a National Surgical Quality Improvement Program database analysis. Surgery 2014 Aug;156(2):352-360.61. Kamolz T, Pointner R, Velanovich V. The impact of gastroesophageal reflux disease on quality of life. Surg Endosc 2003 Aug;17(8):1193-1199.62. Revicki DA, Wood M, Maton PN, Sorensen S. The impact of gastroesophageal reflux disease on health-related quality of life. Am J Med 1998 Mar;104(3):252-258.63. Granderath FA, Kamolz T, Schweiger UM, Pointner R. Quality of life, surgical outcome, and patient satisfaction three years after laparoscopic Nissen fundoplication. World J Surg 2002 Oct;26(10):1234-1238.64. Glise H, Hallerback B, Johansson B. Quality-of-life assessments in evaluation of laparoscopic Rosetti fundoplication. Surg Endosc 1995 Feb;9(2):183-8; discussion 188-9. 65. Yang H, Watson DI, Lally CJ, Devitt PG, Game PA, Jamieson GG. Randomized trial of division versus nondivision of the short gastric vessels during laparoscopic Nissen fundoplication: 10-year outcomes. Ann Surg 2008 Jan;247(1):38-42.66. Velanovich V. Comparison of generic (SF-36) vs. disease-specific (GERD-HRQL) quality-of-life scales for gastroesophageal reflux disease. J Gastrointest Surg 1998 Mar-Apr;2(2):141-145.67. Watson DI, Jamieson GG, Pike GK, Davies N, Richardson M, Devitt PG. Prospective randomized double-blind trial between laparoscopic Nissen fundoplication and anterior partial fundoplication. Br J Surg 1999 Jan;86(1):123-130.68. Rentz AM, Battista C, Trudeau E, Jones R, Robinson P, Sloan S, et al. Symptom and health-related quality-of-life measures for use in selected gastrointestinal disease studies: a review and synthesis of the literature. Pharmacoeconomics 2001;19(4):349-363.69. Johnson WE, Hagen JA, DeMeester TR, Kauer WK, Ritter MP, Peters JH, et al. Outcome of respiratory symptoms after antireflux surgery on patients with gastroesophageal reflux disease. Arch Surg 1996 May;131(5):489-492.70. Chen RY, Thomas RJ. Results of laparoscopic fundoplication where atypical symptoms coexist with oesophageal reflux. Aust N Z J Surg 2000 Dec;70(12):840-842.71. Farrell TM, Richardson WS, Trus TL, Smith CD, Hunter JG. Response of atypical symptoms of gastro-oesophageal reflux to antireflux surgery. Br J Surg 2001 Dec;88(12):1649-1652.72. Novitsky YW, Zawacki JK, Irwin RS, French CT, Hussey VM, Callery MP. Chronic cough due to gastroesophageal reflux disease: efficacy of antireflux surgery. Surg Endosc 2002 Apr;16(4):567-571.73. Allen CJ, Anvari M. Does laparoscopic fundoplication provide long-term control of gastroesophageal reflux related cough? Surg Endosc 2004 Apr;18(4):633-637.74. Kaufman JA, Houghland JE, Quiroga E, Cahill M, Pellegrini CA, Oelschlager BK. Long-term outcomes of laparoscopic antireflux surgery for gastroesophageal reflux disease (GERD)-related airway disorder. Surg Endosc 2006 Dec;20(12):1824-1830.75. Brown SR, Gyawali CP, Melman L, Jenkins ED, Bader J, Frisella MM, et al. Clinical outcomes of atypical extra-esophageal reflux symptoms following laparoscopic antireflux surgery. Surg Endosc 2011 Dec;25(12):3852-3858.76. Ratnasingam D, Irvine T, Thompson SK, Watson DI. Laparoscopic antireflux surgery in patients with throat symptoms: a word of caution. World J Surg 2011 Feb;35(2):342-348.77. Faruqi S, Sedman P, Jackson W, Molyneux I, Morice AH. Fundoplication in chronic intractable cough. Cough 2012 Jul 19;8(1):3-9974-8-3.

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NEDERLANDSE SAMENVATTING

Gastro-oesofageale refluxziekte is een veel voorkomende chronische aandoening in de Westerse wereld.

De belangrijkste klachten zijn zuurbranden met een pijnlijk gevoel achter het borstbeen en oprispingen.

Ongeveer 40% van de bevolking heeft maandelijks dergelijke klachten, 20% wekelijks en 7% dagelijks. De

medicamenteuze behandeling bestaat uit protonpompremmers, die de maagzuursecretie remmen. Deze

middelen zorgen bij 95% van de patiënten voor een langdurige controle van de reflux-klachten, gaan gepaard

met weinig bijwerkingen en bovendien zijn deze medicijnen goedkoop. Echter, bij 5% van de patiënten werken

protonpompremmers niet. Voor deze groep, evenals de patiënten die niet-zure (gallige) reflux hebben,

patiënten met extra-oesofageale klachten (bijvoorbeeld hoesten, heesheid of tanderosie) en patiënten die

niet levenslang protonpompremmers willen slikken, is chirurgische behandeling geïndiceerd. In tegenstelling

tot medicatie, kan een operatie patiënten genezen van hun klachten omdat de anatomie rond de overgang

van de slokdarm naar de maag wordt veranderd. Hier bevindt zich namelijk vaak het onderliggende probleem

van gastro-oesofageale reflux ziekte. De meest geschikte chirurgische antirefluxoperatie is een fundoplicatie.

HOOFDSTUK 1 geeft een overzicht van de huidige kennis en beschrijft de achtergronden van de studies in

dit proefschrift. Tevens worden de doelstellingen van dit proefschrift benoemd aan de hand van vier vragen:

•• Wat is de beste fundoplicatie?

•• Is herstel van een hernia hiatus oesofageï met én zonder mat veilig?

•• Hebben patiënten met chronische hoestklachten baat bij laparoscopische antireflux chirurgie?

•• Wat is de beste methode om de resultaten van laparoscopische antirefluxchirurgie te meten?

LAPAROSCOPISCHE ANTIREFLUX CHIRURGIE

In 1956 is deze operatie voor het eerst beschreven door dr. Nissen in het ‘Schweizer Medizinische

Wochenschrift’. De fundoplicatie beschrijft hij dan als ‘een simpele operatie om reflux te controleren’. De

fundoplicatie beschreven door Nissen betreft een volledige fundoplicatie, waarbij de fundus van de maag

360º om de slokdarm wordt gevouwen. In eerste instantie wordt deze operatie alleen uitgevoerd als laatste

redmiddel bij patiënten met hevige klachten of ernstige complicaties door reflux ziekte. In 1991 werd de eerste

laparoscopische fundoplicatie uitgevoerd, waarbij er veel minder complicaties werden gezien en het herstel

na de operatie versnelde. Sindsdien is de laparoscopische fundoplicatie veel breder toepasbaar. Vanwege

‘post-fundoplicatiesymptomen’ (zoals passageklachten, het onvermogen om te kunnen opboeren, een

opgeblazen gevoel en winderigheid) die veel voorkwamen na de 360º Nissen fundoplicatie, werd er gezocht

naar alternatieven waarbij de fundus gedeeltelijk rond de oesofagus werd geplaatst. Van deze gedeeltelijke

fundoplicaties bleken de 180º anterieure fundoplicatie en de 270º posterieure (Toupet) fundoplicatie de

beste resultaten te geven. Tot nu toe was er geen goed onderzoek verricht waarbij deze twee fundoplicaties

vergeleken werden.

In HOOFDSTUK 2 wordt de MANTA-trial beschreven. Deze dubbel-blinde gerandomiseerde studie

vergelijkt de 180º anterieure fundoplicatie en de 270º posterieure fundoplicatie. De korte termijn resultaten

laten zien dat er geen duidelijk verschil is tussen beide operaties. De passageklachten en andere post-

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fundoplicatiesymptomen zijn gelijk, het verminderen van de refluxklachten is gelijk en patiënten zijn na beide

operaties net zo tevreden. De lange termijn resultaten leveren wellicht meer informatie op en laten misschien

een verschil zien. Tot die tijd kan geconcludeerd worden dat deze enige volledige studie die deze twee

operaties vergelijkt aantoont dat zowel de 180º anterieure fundoplicatie als de 270º posterieure Toupet

fundoplicatie geschikt zijn.

HERNIA HIATUS OESOFAGEÏ

Een middenrifsbreuk (een hernia diafragmatica of in dit geval een hernia hiatus oesofageï) geeft ook

refluxklachten, maar kan ook gepaard gaan met slikklachten (dysfagie). Tegenwoordig bestaat ongeveer

50% van alle laparoscopische antirefluxoperaties uit correcties van een hernia hiatus oesofageï die klachten

geeft. Het herstel van een hernia hiatus oesofageï bestaat uit dissectie van de breukzak en het redresseren

van de gehernieerde abdominale organen vanuit de thorax terug naar het abdomen. Vervolgens wordt een

cruraplastiek verricht met niet-oplosbare hechtingen, waarbij de hernia hiatus oesofageï wordt verkleind. Een

fundoplicatie is ook een belangrijk onderdeel van deze procedure en hierbij geldt ook dat een 180º anterieure

of 270º posterieure fundoplicatie het meest geschikt zijn. De curaplastiek kan verstevigd worden met een

oplosbare of niet-oplosbare mat. Dit is bedacht om het aantal recidieven van een hernia hiatus oesofageï

te verminderen. Helaas kan het gebruik van een mat gepaard gaan met ernstige bijwerkingen. Door de mat

niet in contact te laten komen met de slokdarm komt dit minder voor. Er is nog geen consensus bereikt in de

huidige literatuur of gebruik van een mat bij de cruraplastiek nodig is.

HOOFDSTUK 3 beschrijft een studie waarin een cohort patiënten met cruraplastiek met hechtingen

vergeleken wordt met een cohort patiënten met cruraplastiek met hechtingen én een niet-oplosbare mat.

Hierin wordt duidelijk dat het aantal recidieven dat tot een heroperatie leidt gelijk is in beide groepen. Het

aantal recidieven dat op beeldvorming wordt gezien en niet altijd klachten veroorzaakt is gelijk. En ook het

aantal symptomatische recidieven is gelijk tussen de groep met mat en de groep zonder mat. De kwaliteit van

leven is ook gelijk in beide groepen, net als de patiënttevredenheid en de mate van dysfagie.

HOOFDSTUK 4 beschrijft de subjectieve resultaten van een dubbel-blinde gerandomiseerde studie waarin

drie behandeling werden vergeleken: (1) cruraplastiek met enkel oplosbare hechtingen, (2) cruraplastiek

verstevigd met een oplosbare mat, en (3) cruraplastiek verstevigd met een niet-oplosbare mat. De kwaliteit

van leven verbetert na de operatie en is postoperatief gelijk tussen de drie groepen. Wel bleek er een

significant lagere kwaliteit van leven te zijn bij patiënten met een symptomatische recidief hernia hiatus

oesofageï na de operatie, in vergelijking met zowel patiënten zonder recidief als patiënten met een

asymptomatisch recidief. De bevolking van Westerse landen vergrijst. Aangezien de incidentie van een hernia

hiatus oesofageï toeneemt bij een stijgende leeftijd, zullen er meer oudere patiënten verwezen worden naar

de chirurg voor laparoscopische correctie hiervan. Ouderen hebben vaak meer comorbiditeiten en daardoor

meer kans op complicaties tijdens en na de operatie. HOOFDSTUK 5 beschrijft dat het veilig is om oudere

patiënten met een hiatus hernia oesofageï te opereren, mits de operateur ruime ervaring heeft in het

uitvoeren van deze operaties.

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10

HET METEN VAN RESULTATEN NA LAPAROSCOPISCHE ANTIREFLUX CHIRURGIE

De meeste studies die resultaten van laparoscopische antireflux chirurgie beschrijven richten zich op

objectieve uitkomstmaten. Maar door gebruik te maken van zogenaamde ‘Patient Reported Outcome

Measures’ (PROM’s) wordt een betere weerspiegeling gegeven van wat de operatie heeft betekend voor

de individuele patiënt. Een voorbeeld hiervan is het meten van de kwaliteit van leven. Verscheidene studies

beschrijven het gebruik van de Short Form 36 als uitkomstmaat voor laparoscopische antireflux chirurgie.

In HOOFDSTUK 6 wordt aangetoond dat deze generieke kwaliteit van leven vragenlijst echter niet goed

correleert met de resultaten van de operatie en een ziekte-gerelateerde vragenlijst (zoals de GERD-health-

related-Quality-of-Life questionnaire) en symptoomscores beter gebruikt kunnen worden.

De studie die wordt beschreven in HOOFDSTUK 7 laat zien dat het gebruik van een online systeem om

patiënten automatisch vragenlijsten te sturen via e-mail een veel betere respons oplevert en zorgt voor meer

complete data dan het gebruik van papieren vragenlijsten die via de post gestuurd moeten worden.

CHRONISCHE HOESTKLACHTEN BEHANDELD MET LAPAROSCOPISCHE ANTIREFLUX CHIRURGIE

Chronische hoestklachten kunnen veroorzaakt worden door gastro-oesofageale refluxziekte. In het verleden

zijn wisselende resultaten gepresenteerd van onderzoekers die trachten patiënten met hoestklachten te

behandelen met laparoscopische antireflux chirurgie. Het betreft echter meestal patiënten die primair

refluxklachten als zuurbranden of oprispingen hebben, met daarnaast klachten als hoesten of heesheid.

De enkele studies die wel patiënten beschrijven die geopereerd zijn vanwege primaire hoestklachten maken

gebruik van de laparoscopische Nissen fundoplicatie, waarvan reeds is aangetoond dat deze ondergeschikt is

aan partiële fundoplicaties.

Het cohort van 50 patiënten dat beschreven is in HOOFDSTUK 8 betreft enkel patiënten met primaire

hoestklachten die een partiële 180º anterieure fundoplicatie of een 270º posterieure fundoplicatie hebben

ondergaan. De resultaten zijn goed. Er is een significante afname van hoestklachten op de gevalideerde

Leicester Cough Questionnaire en op de 10-punts hoestscore. Bovendien is er ook een significante

verbetering van de reflux-gerelateerde kwaliteit van leven en zijn de patiënten tevreden. Helaas is er met de

data in deze studie nog geen advies te geven over hoe patiënten met chronische hoestklachten het beste

geselecteerd kunnen worden voor laparoscopische antireflux chirurgie.

Appendices

•• List of abbreviations

••Questionnaires

•• List of publications

141

List of abbreviations

LIST OF ABBREVIATONS

180ºLAF - Laparoscopic 180º anterior fundoplication

95% CI - 95% confidence interval

AF - Atrial fibrillation

ASA - American Society of Anesthesiologists

BMI - Body mass index

COPD - Chronic Obstructive Pulmonary Disease

CRF - Case report form

CT - Computed tomography

GERD-hr-QoL - Gastro-esophageal reflux disease health related quality of life

GOJ - Gastro-oesophageal junction

GORC - Gastro-oesophageal reflux induced chronic cough

GORD - Gastro-oesophageal reflux disease

HH - Hiatal hernia

HHO - Hiatal hernia oesophagei

HLOSP - Hypotensive lower oesophageal sphincter pressure

LARS - Laparoscopic antireflux surgery

LNF - Laparoscopic 360º Nissen fundoplication

LOS - Lower oesophageal sphincter

LTF - Laparoscopic 270º posterior Toupet fundoplication

POH - Para-oesophageal hiatal hernia

PPI - Protonpump inhibitor

PROM’s - Patient reported outcome measures

QoL - Quality of life

RCT - Randomised controlled trial

SD - Standard deviation

SF-36 - Short Form 36

SI-LOSR - Swallow-induced lower oesophageal sphincter relaxation

TLOSR - Transient lower oesophageal sphincter relaxation

Questionnaires

••Quality of care

•• Short Form 36

••GERD-hr-QoL

••OES-24

145

Questionnaires

VRAAG 1 HOOFDKLACHT

Wat was voor de operatie uw belangrijkste klacht?…………………………………………………………………………………………………Kunt U een cijfer van 1 tot 10 geven hoeveel last u had van deze klacht? (1 betekent geen of nauwelijks last en 10 betekent verschrikkelijk veel last)

1 2 3 4 5 6 7 8 9 10

Hoeveel last had U na de operatie nog van deze klacht?…………………………………………………………………………………………………..Kunt U een cijfer van 1 tot 10 geven hoeveel last u had van deze klacht? (1 betekent geen of nauwelijks last en 10 betekent verschrikkelijk veel last) 1 2 3 4 5 6 7 8 9 10

VRAAG 2 ANDERE KLACHTENHad u nog andere klachten voor de operatie?

Klacht 1: ………………………………………………………………………………………………Kunt U een cijfer van 1 tot 10 geven hoeveel last u had van deze klacht? (1 betekent geen of nauwelijks last en 10 betekent verschrikkelijk veel last)

1 2 3 4 5 6 7 8 9 10

Hoeveel last had U na de operatie nog van deze klacht (klacht 1)?…………………………………………………………………………………………………..

Kunt U een cijfer van 1 tot 10 geven hoeveel last u had van deze klacht? (1 betekent geen of nauwelijks last en 10 betekent verschrikkelijk veel last)

1 2 3 4 5 6 7 8 9 10

Klacht 2: ………………………………………………………………………………………………

Kunt U een cijfer van 1 tot 10 geven hoeveel last u had van deze klacht? (1 betekent geen of nauwelijks last en 10 betekent verschrikkelijk veel last)

1 2 3 4 5 6 7 8 9 10 Hoeveel last had U na de operatie nog van deze klacht (klacht 2)?…………………………………………………………………………………………………..Kunt U een cijfer van 1 tot 10 geven hoeveel last u had van deze klacht? (1 betekent geen of nauwelijks last en 10 betekent verschrikkelijk veel last)

1 2 3 4 5 6 7 8 9 10

146

Appendices

Klacht 3: ………………………………………………………………………………………………Kunt U een cijfer van 1 tot 10 geven hoeveel last u had van deze klacht? (1 betekent geen of nauwelijks last en 10 betekent verschrikkelijk veel last) 1 2 3 4 5 6 7 8 9 10

Hoeveel last had U na de operatie nog van deze klacht (klacht 3)?…………………………………………………………………………………………………..Kunt U een cijfer van 1 tot 10 geven hoeveel last u had van deze klacht? (1 betekent geen of nauwelijks last en 10 betekent verschrikkelijk veel last)

1 2 3 4 5 6 7 8 9 10

VRAAG 3 MEDICIJNEN

Gebruikte u voor de operatie een of meerdere zuurremmende medicijnen? Zo ja welke en hoe vaak?

Nexium/ Esomeprazol dagelijks/ zonodig * … x per dag dosis: … mg

Losec/ Omeprazol dagelijks/ zonodig* … x per dag dosis: … mg

Pantozol/Pantoprazol dagelijks/ zonodig* … x per dag dosis: … mg

Zantac/Ranitidine dagelijks/ zonodig* … x per dag dosis: … mgAndere medicijnen voor de maag: ……………………………………………………..* doorhalen wat niet van toepassing is

Gebruikt u na de operatie een of meerdere zuurremmende medicijnen? Zo ja welke en hoe vaak? Nexium/ Esomeprazol dagelijks/ zonodig * … x per dag dosis: … mg

Losec/ Omeprazol dagelijks/ zonodig* … x per dag dosis: … mg

Pantozol/Pantoprazol dagelijks/ zonodig* … x per dag dosis: … mg

Zantac/Ranitidine dagelijks/ zonodig* … x per dag dosis: … mgAndere medicijnen voor de maag: ……………………………………………………..* doorhalen wat niet van toepassing is

VRAAG 4 TEVREDENHEIDKunt U een cijfer van 1 tot 10 geven hoe tevreden u bent met de operatie? (1 betekent zeer ontevreden en 10 zeer tevreden)

1 2 3 4 5 6 7 8 9 10

Nu u weet wat deze operatie voor u heeft gedaan, zou de operatie deze operatie weer ondergaan? Ja / Nee*

147

Questionnaires

Zo niet, wat is daar de reden voor (omcirkel het best passende antwoord): 1. Zware operatie2. Complicaties na de operatie, zijnde ………………………………………………...3. Andere reden, namelijk…………………………………………………………………………

Hoe lang heeft u klachten gehad voor de operatie? ............................maanden/jaar*

Nu u weet wat deze operatie voor u heeft gedaan, zou deze operatie eerder hebben willen ondergaan?Ja/Nee*Zo ja, hoeveel eerder ................................maanden/jaar

Nu u weet wat deze operatie voor u heeft gedaan, zou deze operatie aan een goede bekende of familielid met

een soortgelijke probleem aanraden?Ja / Nee*

Kunt tenslotte rapportcijfers (van 1 tot 10) uitdelen aan de verschillende onderdelen van de zorg?

Wachttijd tot eerste polikliniek bezoek?

1 2 3 4 5 6 7 8 9 10

Poliklinische zorg/ begeleiding?

1 2 3 4 5 6 7 8 9 10

Voorlichting voor de operatie?

1 2 3 4 5 6 7 8 9 10

Wachttijd tot de operatie?

1 2 3 4 5 6 7 8 9 10

Zorg op de verpleegafdeling (vanaf opname tot ontslag)

1 2 3 4 5 6 7 8 9 10

Nazorg op de polikliniek

1 2 3 4 5 6 7 8 9 10

Wij waarderen uw oordeel over de zorg die wij leveren. Als u opmerkingen heeft die niet in de bovenstaande

enquete heeft kunnen uiten dan kunt u hieronder uw opmerkingen kwijt...........................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................

148

Appendices

SHORT FORM 36INSTRUCTIE

Deze vragenlijst gaat over uw standpunten t.a.v. uw gezondheid. Met behulp van deze gegevens kan worden bijgehouden hoe u zich voelt en hoe goed u in staat bent uw gebruikelijke bezigheden uit te voeren.

Beantwoordt elke vraag op de aangegeven manier. Als u een vraag niet precies kunt beantwoorden, geef dan het best mogelijke antwoord.

1. Hoe zou u over het algemeen uw gezondheid noemen? (Omcirkel één cijfer)

Uitstekend……………………………………….. 1

Zeer goed………………………………………… 2

Goed……………………………………………… 3

Redelijk…………………………………………… 4

Slecht……………………………………………... 5

2. Hoe beoordeelt u nu uw gezondheid over het algemeen, vergeleken met een jaar geleden? (Omcirkel één cijfer)

Veel beter dan een jaar geleden…………………... 1

Iets beter dan een jaar geleden…………………… 2

Ongeveer hetzelfde als een jaar geleden…………. 3

Wat slechter dan een jaar geleden……………….. 4

Veel slechter dan een jaar geleden………………. 5

3. De volgende vragen gaan over uw bezigheden die u misschien doet op een willekeurige dag. Wordt

u door uw gezondheid op dit moment beperkt in deze bezigheden? Zo ja, in welke mate?

(Omcirkel één cijfer)

Bezigheden Ja, ernstig beperkt

Ja, een beetje beperkt

Nee, helemaal niet beperkt

Forse inspanning, zoals hardlopen, tillen van zware voorwerpen, een veeleisende sport beoefenen

1 2 3

Matige inspanning, zoals een tafel verplaatsen, stofzuigen, zwemmen of fietsen

1 2 3

Boodschappen tillen of dragen 1 2 3

Een paar trappen oplopen 1 2 3

Eén trap oplopen 1 2 3

Bukken, knielen of hurken 1 2 3

Meer dan een kilometer lopen 1 2 3

Een paar honderd meter lopen 1 2 3

Ongeveer honderd meter lopen 1 2 3

Uzelf wassen of aankleden 1 2 3

149

Questionnaires

4. Heeft u in de afgelopen 4 weken één van de volgende problemen bij uw werk of andere dagelijkse bezigheden gehad, ten gevolge van uw lichamelijke gezondheid?

(Omcirkel één cijfer)

JA NEE

U besteedde minder tijd aan werk of andere bezigheden

U heeft minder bereikt wat u zou willen

U was beperkt in bepaald werk of bij bepaalde andere bezigheden

U had moeite om uw werk of andere bezigheden uit te voeren (het kostte u bijvoorbeeld extra inspanning)

5. Heeft u in de afgelopen 4 weken een van de volgende problemen ondervonden bij uw werk of andere dagelijkse bezigheden ten gevolge van emotionele problemen (zoals depressieve of angstige gevoelens) (Omcirkel één cijfer)

JA NEE

U besteedde minder tijd aan werk of andere dagelijkse bezigheden

U heeft minder bereikt dan u zou willen

U deed uw werk of andere bezigheden niet zo zorgvuldig als gewoonlijk

6. In hoeverre hebben uw lichamelijke gezondheid of emotionele problemen u gedurende de afgelopen 4 weken gehinderd in uw normale omgang met familie, vrienden of buren, of bij activiteiten in groepsverband? (Omcirkel één cijfer)

Helemaal niet……………………………………. 1

Enigszins………………………………………… 2

Nogal……………………………………………. 3

Veel……………………………………………… 4

Heel veel………………………………………… 5

7. Hoeveel lichamelijke pijn heeft u de afgelopen 4 weken gehad? (Omcirkel één cijfer)

Geen……………………………………………... 1

Heel licht………………………………………… 2

Licht……………………………………………... 3

Nogal wat………………………………………... 4

Ernstig…………………………………………… 5

Heel ernstig……………………………………… 6

8. In welke mate bent u de afgelopen 4 weken door pijn gehinderd in uw normale werk (zowel werk

buitenshuis als huishoudelijk werk) (Omcirkel één cijfer)

Helemaal niet……………………………………. 1

Een klein beetje………………………………… 2

Nogal……………………………………………. 3

Vrij veel……….………………………………… 4

Ernstig…………………………………………… 5

150

Appendices

9. Deze vragen gaan over hoe u zich voelt en hoe het met u ging in de afgelopen 4 weken. Geef bij

elke vraag het antwoord dat het best benadert hoe u zich voelde. Hoe vaak gedurende de afge

lopen 4 weken? (Omcirkel één cijfer op elke regel)

De hele tijd

Meestal Vaak Soms Heel soms

Geen enkel moment

Voelde u zich vitaal? 1 2 3 4 5 6

Was u erg zenuwachtig? 1 2 3 4 5 6

Zat u zo in de put dat niets u kon opvrolijken? 1 2 3 4 5 6

Voelde u zich rustig en tevreden? 1 2 3 4 5 6

Had u veel energie? 1 2 3 4 5 6

Voelde u zich somber en neerslachtig? 1 2 3 4 5 6

Voelde u zich uitgeput? 1 2 3 4 5 6

Was u opgewekt? 1 2 3 4 5 6

Voelde u zich moe? 1 2 3 4 5 6

10. Hoe vaak hebben uw lichamelijke gezondheid of emotionele problemen u gedurende de afgelopen 4 weken gehinderd bij uw sociale activiteiten (zoals familie, vrienden, bezoeken, etc.) (Omcirkel één cijfer)

De hele tijd..…….………………………………. 1

Meestal………. ………………………………… 2

Soms.……………………………………………. 3

Heel soms..…….………………………………… 4

Geen enkel moment…………………………… 5

11. Hoe JUIST of ONJUIST is elk van de volgende uitspraken voor u? (Omcirkel één cijfer op elke

regel)

Volkomen juist

Grotendeels juist

Weet ik niet

Grotendeels onjuist

Volkomen onjuist

Ik lijk wat gemakkelijker ziek te worden dan andere mensen

Ik ben even gezond als andere mensen die ik ken

Ik verwacht dat mijn gezondheid achteruit zal gaan

Mijn gezondheid is uitstekend

12. Hoe tevreden bent u met uw huidige toestand? (Omcirkel één antwoord)

Zeer tevreden…………………………… 1

Tevreden………………………………... 2

Neutraal………………………………… 3

Ontevreden……………………………... 4

Zeer ontevreden………………………... 5

151

Questionnaires

13. Heeft u momenteel betaald werk? (Kruis het voor u juiste antwoord aan) ja, mijn beroep is: Zo ja, bent u door uw ziekte genoodzaakt geweest neen om minder uren per week te gaan werken ja

neen Zo nee, in hoeverre wordt dit veroorzaakt door uw volledig gezondheidstoestand? gedeeltelijk helemaal niet

14. Zoals mensen een idee kunnen hebben over de kwaliteit van bijvoorbeeld fruit of wijn, zo kunnen ze ook een idee hebben over de kwaliteit van hun leven. Deze kan heel goed of heel slecht zijn, of ergens er tussenin. Zou u op de lijn hieronder willen aangeven hoe de kwaliteit van uw leven was de afgelopen 4 weken. U doet dat door een kruisje (X) te zetten tussen slechtst denkbare kwaliteit en best denkbare kwaliteit.

Slechts denkbare Best denkbare kwaliteit kwaliteit

15. Als u uw huidige algemene gezondheidstoestand vergelijkt met die van voor de operatie, is deze nu beter geworden

hetzelfde gebleven slechter geworden

16. Als u uw huidige situatie vergelijkt met die van voor de operatie is uw ziekte nu volledig genezen

verbeterd, maar niet genezen onveranderd gebleven slechter geworden

152

Appendices

GERD – HR QOLINSTRUCTIEWilt u alle vragen zelf beantwoorden door het getal te omcirkelen dat het meest op u van toepassing is? Er zijn geen “juiste” of “onjuiste” antwoorden.

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153

Questionnaires

QLQ – OES 24Instructie

Soms zeggen patiënten dat ze de volgende klachten hebben. Wilt u aangeven in welke mate u deze klachten de afgelopen week heeft ervaren?

Gedurende de afgelopen week

Helemaal niet Een beetje Nogal Heel erg

Had u problemen met het eten van vast voedsel? 1 2 3 4

Had u problemen met het eten van gepureerd of gemalen voedsel?

1 2 3 4

Had u problemen met normaal drinken? 1 2 3 4

Had u problemen met het doorslikken van uw speeksel? 1 2 3 4

Heeft u zich verslikt? 1 2 3 4

Had u er moeite mee van uw maaltijden te genieten? 1 2 3 4

Had u te snel een vol gevoel? 1 2 3 4

Had u problemen met eten? 1 2 3 4

Had u problemen om in aanwezigheid van anderen te eten? 1 2 3 4

Had u een droge mond? 1 2 3 4

Had u problemen met smaakvermogen? 1 2 3 4

Had u last van hoesten? 1 2 3 4

Had u moeite met praten? 1 2 3 4

Had u last van oprispingen? 1 2 3 4

Had u indigestie of maagzuur? 1 2 3 4

Had u last van zuur of gal in de mond? 1 2 3 4

Had u pijn tijdens het eten? 1 2 3 4

Had u pijn in uw borst? 1 2 3 4

Had u problemen met boeren? 1 2 3 4

Heeft u meer last van winderigheid dan voor de operatie? 1 2 3 4

Had u pijn in uw maagstreek? 1 2 3 4

Heeft u zich zorgen gemaakt dat uw gewicht te laag was? 1 2 3 4

In welke mate is uw ziekte een belasting voor u? 1 2 3 4

Maakte u zich zorgen over uw gezondheid in de toekomst? 1 2 3 4

List of publications

157

List of publications

LIST OF PUBLICATIONS

Koetje JH, Irvine T, Thompson SK, Devitt PG, Woods SD, Aly A, Jamieson GG, Watson DI.

Quality of Life Following Repair of Large Hiatal Hernia is Improved but not Influenced by Use of Mesh: Results

From a Randomised Controlled Trial.

World J Surg. 2015 Jun;39(6):1465-73

Koetje JH, Ottink KD, Feenstra I, Fritschy WM.

Negative Pressure Incision Management System in the Prevention of Groin Wound Infection in

Vascular Surgery Patients.

Surg Res Pract. 2015;2015:303560

Koetje JH, Nieuwenhuijs VB, Irvine T, Mayne GC, Watson DI.

Measuring Outcomes of Laparoscopic Anti-reflux Surgery: Quality of Life Versus Symptom Scores?

World J Surg. 2016 May;40(5):1137-44

Oor JE, Koetje JH, Roks DJ, Nieuwenhuijs VB, Hazebroek EJ

Laparoscopic Hiatal Hernia Repair in the Elderly Patient.

World J Surg. 2016 Jun;40(6):1404-11

Roks DJ, Koetje JH, Oor JE, Broeders JA, Nieuwenhuijs VB, Hazebroek EJ.

Double-Blind randomised clinical trial of laparoscopic Toupet versus 180º anterior fundoplication for

gastro-oesophageal reflux disease.

Accepted for publication in British Journal of Surgery

Koetje JH, Oor JE, Roks DJ, Van Westreenen HL, Hazebroek EJ, Nieuwenhuijs VB.

Equal patient satisfaction, quality of life and objective recurrence rate after laparoscopic hiatal hernia repair

with and without mesh.

Accepted for publication in Surgical Endoscopy

Koetje JH, Van Dam GM, Dille J, Nieuwenhuijs VB.


Submitted for publication

Koetje JH, Nieuwenhuijs VB, Van Westreenen HL, Patberg KW, Van den Berg JWK.


Submitted for publication

Acknowledgements

Dankwoord

160

Acknowledgements

DANKWOORDMet de proefdruk van dit proefschrift in mijn hand kan ik wel zeggen dat dit boekje bijna ‘klaar’ is. Een heerlijk

gevoel, want ik heb hier jaren hard aan gewerkt. Dat dit onderzoek in een promotie zou resulteren wist niet

iedereen, zelf had ik dat ook niet bedacht toen ik hieraan begon. Het begin van dit promotieonderzoek gaat

terug naar mijn studiejaren in Groningen. Daarom wil ik ook veel mensen bedanken die, wellicht onbewust,

bijgedragen hebben aan dit resultaat. De vage zin “ik moet nog wat doen voor mijn onderzoek” die jullie

waarschijnlijk meermaals van mij gehoord hebben is nu eindelijk tastbaar geworden.

Onderstaande lijst is ongetwijfeld niet compleet, toch wil ik de volgende personen graag hier noemen:

Mijn co-promotor, dr. V.B. Nieuwenhuijs. Beste Vincent, door jouw ideeën, begeleiding en inzet is dit

proefschrift tot stand gekomen. Tijdens mijn coschap bij de chirurgie in het UMCG adviseerde jij mij om

onderzoek te gaan doen. Het begon met het ontwerpen van een eenvoudige website met informatie voor

patiënten over antireflux chirurgie en ging hierna geruisloos over in het bijhouden van een database. Toen ik in

Zwolle mijn coschappen moest lopen volgde jij niet veel later door daar te gaan werken. Een perfecte situatie

om het onderzoek voort te zetten. Jij hebt mij in contact gebracht met professor Watson voor mijn

wetenschappelijke stage in Australië. Terug in Nederland kon ik in Zwolle aan de slag als ANIOS en hebben

wij een plan uitgestippeld voor dit proefschrift. Met strakke deadlines en veel motiverende gesprekken, maar

vooral door veel vertrouwen in mij heb jij ervoor gezorgd dat mij dit gelukt is. Bij de overdrachten en de

besprekingen van de manuscripten let jij altijd op de spelling en grammatica. Regelmatig heb ik "taal is belan-

grijk" van je gehoord, een zin die ik vaak herhaal en probeer goed toe te passen. Vincent, ik wil je danken voor

alle ruimte en alle kansen die je mij hebt gegeven. Ik hoop nog lang met je te mogen samenwerken, zowel op

chirurgisch als op wetenschappelijk gebied.

Mijn promotor, hooggeleerde prof. dr. G.M. van Dam. Beste Go, jij was direct enthousiast toen Vincent

en ik onze plannen met jouw besproken. Door jouw goede adviezen, coördinatie en visie is dit proefschrift

realiteit geworden. Bedankt voor al je hulp.

Hooggeleerde leden van de beoordelingscommissie, prof. dr. J.H. Kleibeuker, prof. dr. M.P. Schijven,

prof. dr. D.I. Watson. Hartelijk dank voor jullie kritische en snelle beoordeling.

Highly learned prof. dr. D.I. Watson, dear David. It is an honour to welcome you in The Netherlands in

November to join my defence and the symposium we have organised. During my time at Flinders Medical

Center in Adelaide, you always created moments to discuss the progress of the studies I worked on. Because

of your expertise, patience, and quick responses I could write two manuscripts in that short period, of which

one was accepted outright (the ‘clean slate’). Many thanks for all your help and advices for finishing this

thesis.

Collega’s uit Nieuwegein, dr. E.J. Hazebroek, J.E. Oor, D.J. Roks, beste Eric, Jelmer en David. Zonder de

samenwerking met jullie was dit proefschrift niet volledig. Hartelijk dank voor de mogelijkheden om samen te

schrijven, data te verzamelen en wederzijds mee te werken aan de studies. Een vruchtbare samenwerking, die

hopelijk in de toekomst tot meer mooie resultaten zal leiden.

161

Dankwoord

Mrs. T. Irvine, dear Tanya. I would like to thank you for all the help regarding the database and for tracing

and resolving the odd, outlying scores of the Australian cohort.

Dr. G.C. Mayne, dear George. Heaps of thanks for all the help and advice on the statistics and with SPSS,

for supplying technical support, guiding me through the hospital and all the inspiring travel tips for Australia.

Dr. H.L. van Westreenen, beste Erik. De laatste jaren ben jij ook nauw betrokken geraakt bij de “antireflux

kliniek” in Zwolle. Ook op wetenschappelijk gebied ben jij erg betrokken geraakt. Bedankt voor je mateloze

enthousiasme en het snel nakijken van de manuscripten.

Annalie Joldersma, bedankt voor je betrokkenheid bij de follow-up van de patiënten en je scherpte op het

voltooien van de vragenlijsten. Daarnaast was je op een goede manier kritisch over hoe dit proces verbeterd

kon worden, wat onder andere resulteerde in de ‘fundo-bespreking’.

Dr. J.W.K. van den Berg, dr. K.W. Patberg. Hartelijk dank voor jullie samenwerking met betrekking tot

hoofdstuk 8. De follow-up is nog kort en de patiëntengroep nog klein, maar de resultaten zijn veelbelovend.

Dit krijgt ongetwijfeld een vervolg.

Dr. J.G.M. Burgerhof, Sander Brink, Mireille Edens. Bedankt voor jullie adviezen met betrekking tot de

studie-opzet en statistiek.

De personen achter de Research Manager. Bedankt voor jullie begeleiding en adviezen met betrekking tot

de online follow-up en de opzet van de databases.

Tom Huisman. Voor mijn gevoel ben jij altijd in de DISC (medische bibliotheek in de Isala) te vinden. Je

hebt vaak geholpen met het zoeken naar de volledige manuscripten van titels waar ik niet verder mee kwam

en attendeerde mij regelmatig op ander materiaal dat bruikbaar was. Altijd positief en ontzettend snel met

reageren. Bedankt!

All other co-authors, J. Dille, dr. J.A. Broeders, dr. S.K. Thompson, dr. P.G. Devitt, dr. S.D. Woods,

dr. A.Aly, dr. G.G. Jamieson. Thanks for the contribution to the relevant manuscripts.

Alle chirurgen en collega arts-assistenten in Zwolle. Bedankt voor al jullie bijdragen aan dit proefschrift,

mijn werkplezier, de opleidingsmomenten en de vele gezellige momenten in de kliniek, maar ook vooral

daarbuiten.

Alle secretaresses, verpleegkundigen en doktersassistentes op de poli, het secretariaat en de

afdelingen: bedankt voor jullie hulp en bijdragen. Door jullie inzet zijn veel vragenlijsten ingevuld.

Stans, in het bijzonder een dankwoord voor jou. Voordat ik er naar kon vragen had jij de vragenlijsten alweer

verwerkt en zorgde jij ervoor dat de juiste patiënten de vragenlijsten ontvingen en deze ingevuld weer bij mij

terecht kwamen.

162

Acknowledgements

Fiets-maten, oud-teamgenoten, oud-commissie- en bestuursleden, oud-huisgenoten, medemusici

en alle andere vrienden en vriendinnen. Door alle mooie momenten samen op de fiets, op het veld, in

het clubhuis, op het podium, thuis op de bank, aan de bar of ergens anders kreeg ik weer energie om aan dit

project te werken. Bedankt daarvoor!

Housemates at 52 Pier Street in Glenelg. Thanks for all the great fun! I will never forget the Christmas that

we spent together. You made my time Down Under unforgettable.

Groove Department, beste bandleden Eric, Nico, SJ, Folkert, Jart, Floris, Hans O. Maaike, fantastische

geluidsmannen Hans W. en Gup en niet te vergeten oud-bandgenoot Pieter. Het is heerlijk om met jullie op

het podium te staan en van ieder optreden weer een feest te maken. Al negen jaar maken wij samen muziek

en is het ook backstage gezellig. Elke verandering is tot nu toe spannend geweest, maar ik hoop dat wij nog

heel veel jaren door kunnen gaan. Bedankt voor alle mooie momenten en al jullie begrip als ik weer druk met

andere zaken was. Bert de Vries, ik wil jou bedanken voor alle keren dat jij voor mij hebt willen invallen.

Jeroen, Wouter, Rolf, Matthijs, Pascal, Jart, Floris. Jeroen en Wouter: wij gaan snel die triatlon doen! Jart,

daarna wat drinken kan ook hoor. Matthijs, Pascal, Floris: wij zijn nu alle vier in opleiding tot chirurg: prachtig!

Wij gaan nog vele congressen samen meemaken. Rolf, een jaar huisgenoten geweest in Zwolle. Mooi dat jij bij

mijn promotie/feest bent, voor die van jou kom ik graag opnieuw naar Marseille.

Mannen, het wordt hoog tijd om weer eens met zijn allen weg te gaan, jullie zijn geweldige vrienden. Sinds

onze studententijd is er veel veranderd, maar nog steeds herleven oude tijden zodra wij samen zijn. Bedankt

voor jullie steun en begrip als ik toch weer eens af moest haken.. jullie zien nu waar het voor geweest is!

Rude, Stoof, Kraker, Borrel, Dirkic, Wallie, Serboss, PP, Spits. Met Gieren 3 als basis. Het

maandelijkse diner sinds het vertrek uit Groningen heeft nog niet helemaal zijn regelmaat gevonden. Gelukkig

hebben wij sindsdien nog wel wat mooie tripjes gemaakt die altijd voor de broodnodige ontspanning zorgen.

Bedankt voor de mooie onvergetelijke momenten, dat er nog maar veel mogen volgen.

Mijn paranimfen, Jart en Floris. Op de middelbare school in Sneek waren wij klasgenoten en al snel

vrienden. Samen speelden wij in de Bogerman Bigband en begonnen wij ons eigen funkbandje. Met zijn

drieën zijn wij geneeskunde gaan studeren in Groningen waar wij al snel onze band Groove Department

oprichtten. Daarna met zijn drieën coschappen lopen in Zwolle.

Jart, jij bent altijd eerlijk en duidelijk en dat waardeer ik enorm. Als je iets doet neem je dat serieus en doe je

het grondig. Zo heb jij mij ook fantastisch geholpen met enkele hoofdstukken uit dit proefschrift.

Floris, onze vriendschap is als onze zeilboot. Al heel oud, er is veel aan veranderd, maar hij het gaat nog altijd

voor de wind. Samen klussen, sporten, muziek maken of niets doen: Hakuna Matata!

Opa en oma en pake en beppe. Ik ben trots dat ik dit moment met jullie mag vieren.

163

Dankwoord

Pieter en Margriet. Met jullie als schoonouders heb ik veel geluk. Behalve dat jullie een fantastische dochter

hebben, zijn jullie ook altijd bereid om te helpen met van alles en nog wat. Dat heeft er zeker voor gezorgd dat

ik dit proefschrift heb kunnen afronden. Bedankt!

Gert en Maaike, lieve broer en zus. Het is heerlijk om met jullie weer eens lekker ‘thuis’ te zijn en dan ook

even niet over ‘de geneeskunde’ te praten maar te gaan sporten of de stad in te gaan. Nu dit proefschrift klaar

is heb ik daar hopelijk vaker tijd voor!

Papa en mama. Wat ben ik ontzettend blij met jullie als ouders. Jullie hebben mij altijd alle ruimte gegeven

om mijn dingen te doen. Wellicht begrijpen jullie niet altijd waar ik nu allemaal mee bezig ben, maar jullie

steunen mij in alles. Mama, je bent altijd gastvrij en staat altijd klaar met goede adviezen, zonder mij te

remmen of opdringerig te zijn. En papa, altijd geïnteresseerd en nieuwsgierig. Ook bij dit schrijfwerk heb je

weer met goede feedback geholpen! Hopelijk kan ik net zo’n goede ouder zijn als jullie!

Maaike, allerliefste Maaike. Waar zou ik zijn zonder jou? Wij zijn al vele jaren gelukkig samen en binnenkort

met zijn drieën! Ik geniet van alle tijd die wij samen doorbrengen. Jij geeft mij de ruimte om zo nu en dan hard

te werken, maar weet mij ook altijd op de juiste momenten te doordringen van de noodzaak om te genieten

van het leven en te ontspannen. De afgelopen periode heb je mij aan alle kanten ondersteund, terwijl ik

eigenlijk voor jou had moeten zorgen. Als een soort eindredacteur heb jij mij met dit proefschrift geholpen.

Bedankt voor alle liefde en blijdschap die jij mij geeft. Ik hoop voor altijd bij jou te mogen blijven!

Curriculum VitaeAuctoris

167

Curriculum vitae auctoris

CURRICULUM VITAE AUCTORIS

Jan Harm Koetje werd op 15 juli 1988 geboren in Winschoten. Hij groeide op in Sneek en behaalde aldaar op

het Bogerman College zijn gymnasium diploma. In 2006 is hij gestart met de studie Geneeskunde aan de

Rijksuniversiteit te Groningen. Tijdens zijn bachelor heeft hij onderzoekservaring opgedaan bij verschillende

projecten in het UMCG, deed hij tweemaal een medische stage in Tanzania en was hij een jaar bestuurslid van

studentenhockeyvereniging G.C.H.C.. Tevens was hij actief saxofonist en contactpersoon van de band ‘Groove

Department’.

Tijdens zijn eerste coschap bij de abdominale chirurgie in het UMCG werd hij enthousiast voor het heelkunde

vak en is onder leiding van dr. Vincent Nieuwenhuijs een onderzoeksproject begonnen, het begin van dit

proefschrift (promotor prof.dr. G.M. van Dam). Na zijn coschappen in de Isala in Zwolle heeft hij zijn keuze-co-

schap op de intensive care en de afdeling chirurgie gevolgd, eveneens in de Isala in Zwolle. Vervolgens heeft

hij zijn studie op 11-12-'13 afgerond met een wetenschappelijke stage in Adelaide, Australië, onder leiding van

prof.dr. D.I. Watson.

Vanaf april 2014 werkte Jan als ANIOS bij de chirurgie in Isala te Zwolle en vanaf 1 januari 2016 is hij in

opleiding tot chirurg. In 2014 is Jan benoemd tot 'Werkpaard van Isala', een prijs die jaarlijks uitgereikt wordt

aan een arts-assistent die naast klinisch werk veel onderzoek verricht. Tijdens deze uitreiking op de

Wetenschapsavond van Isala ontving hij tevens de prijs voor 'Beste posterpresentatie'. In 2015 heeft hij op het

NVEC congres in de Beurs van Berlage in Amsterdam de prijs voor 'Meest innovatieve onderzoek' gewonnen

met de studie naar de online follow-up na antireflux chirurgie.

Naast zijn studie en werk is Jan saxofonist, sport hij veel waaronder wielrennen en hardlopen en als er niet

geklust moet worden aan de boot, zeilt hij graag. Ook heeft hij in verscheidene commissies en besturen gezeten.

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The follow-up and results of laparoscopic

antireflux surgery

Jan Harm Koetje

the of laparoscopic antireﬂux surgery · accepted british journal of surgery chapter 3: equal...

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