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GLOBAL VALUE DOSSIER FOR MINIMALLY INVASIVE SURGERY (MIS)
NISSEN FUNDOPLICATION
Global Value Dossier: Nissen Fundoplication 2
Prepared by: Jayne Smith-Palmer and William Valentine
Ossian Health Economics and Communications, Bäumleingasse 20, 4051 Basel, Switzerland
Phone: +41 61 271 6214
E-mail: [email protected]
Version No. 2.1
Date: April 02, 2016
Global Value Dossier: Nissen Fundoplication 3
Contents
1. Nissen fundoplication ........................................................................................................ 4
1.1. Overview of procedure .............................................................................................. 4
1.2. Clinical and economic outcomes associated with laparoscopic versus open fundoplication ............................................................................................................ 7
1.1.1. Clinical and economic evidence tables for fundoplication .............................. 11
1.3. References ............................................................................................................... 18
List of Tables
Table 7-1 Summary of key meta-analyses studies comparing open versus laparoscopic fundoplication ...................................................................................................... 11
Table 7-2 Summary of key clinical studies comparing open versus laparoscopic fundoplication ...................................................................................................... 12
Table 7-3 Summary of key studies comparing economic outcomes of open versus laparoscopic fundoplication ................................................................................. 16
List of Figures
Figure 1-1 Laparoscopic Nissen and Troupet fundoplication ............................................ 5
Figure 1-2 Laparoscopic ort positions for fundoplication .................................................. 6
Figure 1-3 Length of hospital stay with open versus laparoscopic fundoplication ............ 9
Figure 1-4 Patient evaluation of surgical result for laparscopic versus open Nissen fundoplication .................................................................................................. 10
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1. Nissen fundoplication
1.1. Overview of procedure
Gastro-esophageal reflux disease (GERD) is a relatively common condition in the Western world, with a prevalence ranging between 10% and 20% in Europe and North America.1 It can have a substantial impact on quality of life, as sufferers often experience sleep disturbance, lower concentration and difficulties with exercise.2 If the condition is left untreated, persistent GERD can lead to complications such as ulceration, erosive esophagitis, esophageal strictures, hemorrhage and, ultimately, esophageal adenocarcinoma.3 Treatment commonly depends on the severity of symptoms, and includes both medical and surgical management. The majority of individuals with GERD use regular or continuous medication, particularly proton pump inhibitors, to suppress acid production and control the condition. Although these medicines are generally considered to be safe and effective, questions have been raised regarding the long-term side-effects of prolonged acid suppression.4 Moreover, pharmacotherapy to control the symptoms of GERD do not result in regression of Barrett's esophagus and as a result the risk of cancer is not eliminated by any of these treatments.
Rudolph Nissen was the first to pioneer antireflux surgery in 1956, pioneering the approach in which the fundus of the stomach is wrapped around the lower end of the esophagus and stitched in place, reinforcing the closing function of the lower esophageal sphincter and preventing the reflux of gastric acid.5 Nissen’s initial technique would come to be modified several times in subsequent decade, including the first laparoscopic procedures in 1991 by Dallemagne, and currently a range of different procedures are used regarding the wrap (total, partial anterior, or partial posterior) and the technique (open or laparoscopic fundoplication).6,7,8
Medical therapy is the first line of management for GERD.9 Since it is a chronic condition, medical therapy involving acid suppression and/or pro-motility agents may be required for the rest of a patient's life. Despite the fact that current medical management is very effective for the majority a small number of patients do not get complete relief of symptoms and, as a result, there is increasing interest in the surgical management of GERD. It has been estimated that between 10 and 50% of patients with GERD require long-term treatment or surgical intervention.9 However, referral rates remain low (approximately 3%) due to concerns around negative outcomes including bloating, inability to belch and inability to vomit. Indications for surgical management of GERD are:10
Failed medical management (inadequate symptom control, severe regurgitation not controlled with acid suppression, or medication side effects)
Patients who opt for surgery despite successful medical management (due to quality of life considerations, life-long need for medication intake, expense of medication etc.)
Complications of GERD (Barrett's esophagus, peptic stricture)
Extraesophageal manifestations, e.g. the coexistence of Barrett's esophagus with reflux symptoms is considered by many as clear indication for antireflux surgery
The widespread availability of laparoscopic technology may well have increased the overall numbers of Nissen fundoplication procedures for GERD. For example, data from Finland directly supports this assertion.11 The fundoplication rate per 100,000 population rose from 8.8 to 15.4 between 1988 and 1993, leading to 784 fundoplications and 43 other antireflux procedures being performed in a total population of approximately 5 million in 1993. There are currently two main methods of fundoplication in common use:
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Classical open methods
Laparoscopic techniques
In both procedures, the fundus of the stomach, which is on the left of the esophagus and main portion of the stomach, is wrapped around the back of the esophagus until it is once again in front of the structure (Figure 1-1 and Figure 1-2).9 The portion of the fundus that is now on the right side of the esophagus is sutured to the portion on the left side to keep the wrap in place. This has the effect of creating a one way valve in the esophagus to allow food to pass into the stomach, but prevents stomach acid from flowing into the esophagus and thus preventing GERD.
Following tissue dissection and mobilization, the lesser sac is opened and a sling inserted round behind the esophagus and held up with forceps. Graspers are then used to wrap the fundus, by pulling the tip, around the esophagus and the crura is approximated behind the esophagus using two or three sutures. The fundus is then sutured to the crura to hold it in place and the sling is removed before closing. Five ports are recommended to complete the
procedure laparoscopically (Figure 1-2).
Figure 1-1 Laparoscopic Nissen and Troupet fundoplication
The upper panel shows the 360 degree Nissen fundoplication where the fundus of the stomach is wrapped fully round the esophagus and sutured. The lower panel shower Toupet fundoplication, a 270 degree posterior wrap of the fundus, which is preferred in some cases due to reduced complication rates (e.g. gas bloat, gagging and dysphasia).9
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Figure 1-2 Laparoscopic port positions for fundoplication
Five ports are recommended for the laparoscopic procedure: 1) 10mm camera port 5cm above the umbilicus; 2) 5mm port in the right upper quadrant, 3) variable 5-10 mm is in the left upper quadrant - a mirror image of the one on the patient's right; 4) Nathanson liver retractor is inserted through a 5 mm incision in the midline, extending from skin to the peritoneal cavity; and 5) 5 mm port is positioned in the left mid clavicular line immediately below the costal margin. This port is mainly used for a forceps which will hold the tape encircling the esophagus.9
Laparoscopic fundoplication is a useful method for reducing hospital stay, complications and return to normal activity.
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1.2. Clinical and economic outcomes associated with laparoscopic versus open fundoplication
Key findings
Clinical outcomes
Length of stay: Laparoscopic fundoplication was associated with a significantly shorter LoS than open surgery in six out of seven studies where it was reported (
Figure 1-3)12,15,16,22,23,24
Operating time: Operating times were longer for laparoscopic fundoplication in studies in the US and UK14,22, but no significant differences was reported in other studies12,16,17,,24
GERD symptoms: The resolution of reflux symptoms was comparable across four studies with open and laparoscopic surgery both short- and long-term,20,21,22,24 with two further analysis providing conflicting evidence13,16
Mortality: Mortality rates were low in all of the studies identified and no significant differences in mortality rates were reported
Post-operative pain: Significantly less wound pain was reported following laparoscopic than open fundoplication22
Re-intervention: Two studies reported no significance difference in re-intervention rates13,14, and one study indicated that significantly more patients underwent reoperation after open than laparoscopic fundoplication (however the mean interval between operation and re-intervention was longer after open surgery)21
Patient satisfaction: Long-term patient satisfaction was significantly higher in laparoscopic fundoplication patients than in those who underwent open surgery,20 though no difference was reported in other studies13,16,19,22
Economic outcomes
Total costs: Findings from studies reporting economic data are inconsistent o United States: Data from the US has shown that total hospital costs may
be lower with laparoscopic surgery15 but that surgical costs are likely to be higher than with open surgery.14,15
o Europe: Laparoscopic fundoplication was found to be cost-effective in the Netherlands and cost saving in Sweden compared with open surgery.23,24
Savings due to clinical benefits: Clinical benefits of laparoscopic Nissen fundoplication, including shorter length of hospital stay have been shown to translate into economic benefits (cost savings from the payer perspective) in the US).15
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Other findings
Proton pump inhibitor use: Long-term studies have shown a trend towards an increasing need for the regular use of a proton pump inhibitor with the passage of time after both open and closed Nissen fundoplication.20
Long-term outcomes: Long-term symptomatic outcomes of open and laparoscopic Nissen fundoplication appear to remain unaltered after the first 10 post-operative years.16,20
Surgeon volume: Laparoscopic operating time decreased as surgeons became more experienced with the procedure, which would have significant benefits in terms of health economic and, potentially, clinical outcomes.22
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Figure 1-3 Length of hospital stay with open versus laparoscopic fundoplication
NR, not reported. Blomqvist p=NR, Ackroyd p=<0.001, Draaisma p=0.029, Fox p=NR, Ruiz-Tover P=<0.001.
8.0
5.0
5.8
10.09.5
2.0
3.0
4.54.0
3.0
Blomqvist et al.1998
Ackroyd et al.2004
Draaisma et al.2006
Fox et al. 2010 Ruiz-Tover et al.2010
Le
ng
th o
f h
osp
ita
l sta
y (
da
ys)
Open Laparoscopic
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Figure 1-4 Patient evaluation of surgical result for laparoscopic versus open Nissen fundoplication
31.6
29.0
15.8
18.4
5.2
41.7
38.0
13.0
6.3
2.1
Excellent Good Satisfactory Fair Poor
Pa
tie
nt
ev
alu
ati
on
of
surg
ica
l re
sult
(%)
Open Laparoscopic
p=0.0484 for difference between groups on total excellent or good evaluations. Source: Salminen et al. 2012 (20)
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1.1.1. Clinical and economic evidence tables for fundoplication
Table 1-1 Summary of key meta-analyses studies comparing open versus laparoscopic fundoplication
Authors Details Procedures Outcome Standardized mean differences (95% CI)
P value
Siddiqui et al. 201112 6 studies of which 4 were retrospective studies and two were prospective trials (466 patients in the laparoscopic group and 255 in the open group)
Open versus laparoscopic Nissen fundoplication for GERD in children
Operative time (hours) Hospital stay (days) Start of feeding (hours) 30-day morbidity 12-month recurrence
−0.55 (−1.69, 0.60), no significant difference 0.93 (0.41, 1.44) shorter with laparoscopy 4.13 (1.00, 7.27) sooner with laparoscopy Relative risk 3.22 (1.98,5.25) higher with open Relative risk 2.49 (0.50, 12.37), no significant difference
0.35 0.93 <0.01 <0.01 0.26
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Table 1-2 Summary of key clinical studies comparing open versus laparoscopic fundoplication Study Setting Study details Procedure (year
performed) Summary of clinical findings
Endpoint Open MIS P value
Fyhn et al. 201513
Norway RCT in children, n=43 open, n=44 laparoscopic, 4 years follow up
Laparoscopic versus open Nissen fundoplication (2003–2009)
Post-operative Recurrence of GERD, % Repeat fundoplication, % Able to burp, % Increased flatulence, % Retching (4-7 days/week), % Meal-related discomfort, % Improved well-being, %
7 17 71% 67 11 25 97
37 5 92 57 0 29 100
0.001 0.16 0.05 NS NS NS NS
Papandria et al. 201514
United States
RCT in children <2 years old, n=21 open, n=18 laparoscopic
Laparoscopic versus open Nissen fundoplication (2005–2012)
Operative and peri-operative outcomes Median operating room time (minutes) Median surgery length (minutes) Median duration of epidural catheter (days) Median duration of narcotic use (days) Median time to full enteral feeds (days) Median LoS (days) Median operating room charges (USD) Median total hospital charges (USD) 30-day re-admissions, % Post-operative outcomes Mortality, % Re-operation, %
165 91 2 3 3 4 2,722 13,906 13.6 14 4
209 173 2 4 4 6 4,450 26,445 29.4 18 12
0.002 <0.001 0.78 0.26 0.91 0.08 0.002 0.18 0.26 0.99 0.57
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Table 1-2 Summary of key clinical studies comparing open versus laparoscopic fundoplication Study Setting Study details Procedure (year
performed) Summary of clinical findings
Endpoint Open MIS P value
Continued symptomatic reflux, % Antacid use, %
4 68
6 76
0.99 0.72
Fox et al. 201015
United States
Retrospective database analysis in children, n=3,105 open, n=3,978 laparoscopic
Laparoscopic versus open Nissen fundoplication (2005–2008)
Unadjusted outcomes Infection, % Surgical complications, % Post-procedure length of stay (days) Total LoS (days) Total costs (USD)
27.6 25.5 6 10 22,487
15.7 12.0 3 4 13,003
NA NA NA NA NA
Ruiz-Tover et al. 201016
Spain Retrospective database analysis, n=88 open, n=78 laparoscopic
Laparoscopic versus open Nissen fundoplication (1996–1998)
Mean surgical time (minutes) Complication rate, % Median post-operative stay (days) Post-operative (10 years) Occasional symptoms (e.g. heartburn/regurgitation), % Proton pump inhibitor, % Increased abdominal meteorism or flatulence, % Satisfaction rate, %
151 5 9.5 24 16 34 96
142 5 3 11 7 40 97
NS NS <0.001 <0.05 <0.05 NS NS
Thatch et al. 201017
United States
Retrospective medical records review, n=32 open, n=25 laparoscopic
Laparoscopic versus open Nissen fundoplication (2002–2008)
Time to goal feed (days) 24-hour post-operative narcotics (mg/kg) Blood loss (mL) Surgical time (minutes)
6.1 0.55 13 111
4.3 0.24 11 113
0.04 0.007 0.33 0.76
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Table 1-2 Summary of key clinical studies comparing open versus laparoscopic fundoplication Study Setting Study details Procedure (year
performed) Summary of clinical findings
Endpoint Open MIS P value
Knatten et al. 201418
Norway RCT in children, n=13 open, n=16 laparoscopic
Laparoscopic versus open Nissen fundoplication (2003–2007)
Post-operative (3 days) Pulmonary complications, % Gastrostomy infection, % Blood transfusion, % Repeat gastrostomy, % Other complications Infection, %
6 6 12 6 25
46 0 15 0 46
NR NR NR NR NR
Pacilli et al. 201419
United Kingdom
RCT in children, n=20 open, n=19 laparoscopic
Laparoscopic (n=15) versus open (n=16) Nissen fundoplication (2008–2009)
Post-operative Retching, % Gas bloat syndrome, % Dumping syndrome, % Any of the above, %
50 31 6 56
7 13 6 27
0.01 NS NS NS
Salminen et al. 201220
Finland RCT, n=38 open, n=86 laparoscopic
Laparoscopic versus open Nissen fundoplication (1992–1995)
Post-operative Positive evaluation of surgical result, % Barrett's esophagus, % Hiatal hernia, % Partial plication disruption, % Total plication disruption, % Would choose surgery again, %
76 7.1 57 32.1 14.3 66
92 19.4 31 8.3 2.8 77
0.0484 0.2778 0.0326 0.0035 0.0035 0.1384
Broeders et al. 200921
Netherlands RCT, n=69 open, n=79 laparoscopic
Laparoscopic versus open Nissen fundoplication (1997–1999)
Post-operative GERD symptoms relieved, % Relief of regurgitation, % Quality of life (VAS) Would choose surgery again, % Re-operation, % Mean interval between surgery and reintervention
91 91 61 73 34.8 50.6 months
92 99 65 79 15.2 22.9 months
NS 0.030 NS NS 0.006 0.047
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Table 1-2 Summary of key clinical studies comparing open versus laparoscopic fundoplication Study Setting Study details Procedure (year
performed) Summary of clinical findings
Endpoint Open MIS P value
Ackroyd et al. 200422
United Kingdom
RCT, n=47 open, n=52 laparoscopic
Laparoscopic versus open Nissen fundoplication (dates not reported)
Peri-operative Median operating time, minutes Time to oral fluid intake Time to solid food intake LoS Recovery time Post-operative Positive outcome at 12 months, % Median acid exposure times (pH<4), % Median reflux episodes Amplitude distal esophageal motility, mmHg
46 1 day 2 days 5 days 7 weeks 91 0.4 3 (0, 27) 70.5
82 1 day 2 days 4 days 4 weeks 90 0.1 1 (0, 17) 80
0.001 0.084 0.004 <0.001 0.002 NS 0.250 0.169 0.038
LoS, length of stay; RCT, randomized controlled trial.
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Table 1-3 Summary of key studies comparing economic outcomes of open versus laparoscopic fundoplication Study Setting Study details Procedures Currency
(Cost year) Cost Outcome Open Laparoscopic P value
Draaisma et al. 200623
Netherlands Cost-effectiveness analysis based on RCT and cohort study data n=46 open, n=57 laparoscopic, plus n=121 laparoscopic from the cohort study
Laparoscopic versus open Nissen fundoplication (1997–1999)
EUR (2004) Open versus laparoscopic Nissen fundoplication, RCT mean hospital costs Cohort mean hospital costs RCT mean sick leave costs Cohort mean hospital costs RCT mean total costs Cohort mean total costs RCT mean QALYs in one year (VAS) Cohort mean QALYs in one year RCT ICER (cost per QALY gained) Cohort ICER (cost per QALY gained)
6,989 6,951 13,940 0.59
9,126 7,782 6,351 6,560 15,477 14,342 0.63 0.66 ≈38,400 ≈5,700
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Table 1-3 Summary of key studies comparing economic outcomes of open versus laparoscopic fundoplication Study Setting Study details Procedures Currency
(Cost year) Cost Outcome Open Laparoscopic P value
Blomqvist et al. 199824
Sweden Prospective observational study, n=28 open, n=28 laparoscopic
Laparoscopic versus open fundoplication (1991–1993)
SEK (1995) Direct costs Laboratory tests Blood transfusions Post-op recovery unit Operating theatre Disposables Hospital stay Doctors' visits Endoscopies Total direct costs Indirect costs Lost productivity due to surgery, doctors' visits and endoscopies Total costs
664 189 3,677 12,856 0 18,102 1,929 65 37,482 37,126 74,608
157 12 1,481 18,363 5,850 5,558 1,993 129 27,693 12,596 40,289
EUR, Euros; ICER, incremental cost-effectiveness ratio; RCT, randomized controlled trial; QALY, quality-adjusted life year; SEK, Swedish Kronor
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1.3. References
1 Dent J, El-Serag HB, Wallander MA, JohanssonS. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 2005; 54: 710–712 (PMID:15831922)
2 Quigley EM, Hungin AP. Review article:quality-of-life issues in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2005; 22: 41–47 (PMID: 16042658)
3 Pisegna J, Holtmann G, Howden CW, Katelaris PH, Sharma P, Spechler S et al. Review article: oesophageal complications and consequences of persistent gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2004; 20(Suppl 9): 47 – 56 (PMID: 15527464)
4 Ali T, Roberts DN, Tierney WM. Long-term safety concerns with proton pump inhibitors. Am J Med 2009; 122: 896 – 903 (PMID: 19786155)
5 Nissen R. Eine einfache Operation zur Beeinflussung der Re- fluxoesophagitis. Schweiz Med Wochenschr. 1956; 86: 590–592. (PMID: 13337262)
6 Dallemagne B, Weerts JM, Jehaes C, Markiewicz S, Lombard R. Laparoscopic Nissen fundoplication: preliminary report. Surg Laparosc Endosc. 1991; 1(3): 138–143. (PMID: 1669393)
7 Neufel M, Graham A. Levels of evidence available for techniques in antireflux surgery. Dis Esophagus 2007; 20: 161–167 (PMID: 17439601)
8 Koch OO, Kaindlstorfer A, Antoniou SA, Luketina RR, Em- manuel K, Pointner R. Comparison of results from a ran- domized trial 1 year after laparoscopic Nissen and Toupet fundoplications. Surg Endosc 2013; 27(7): 2383–2390 (PMID: 23361260)
9 World Laproscopy Hospital Online. How to do laparoscopic fundoplication? Available at: http://www.laparoscopyhospital.com/lap_fundo.htm [Last accessed December 18, 2015]
10 Nwokediuko SC. Current Trends in the Management of Gastroesophageal Reflux Disease: A Review. ISRN Gastroenterol. 2012; 2012: 391631 (PMCID: PMC3401535)
11 Viljakka M, Luostarinen M, Isolauri J. Incidence of Antireflux Surgery in Finland 1988-1993: Influence of Proton-Pump Inhibitors and Laparoscopic Technique. Scand J Gastroenterol 1997; 32(5): DOI:10.3109/00365529709025074
12 Siddiqui MRS, Abdulaal Y, Nisar A, Ali H, Hasan F. A meta-analysis of outcomes after open and laparoscopic Nissen’s fundoplication for gastro-oesophageal reflux disease in children. Pediatr Surg Int (2011) 27:359–366. (PMID: 20734053)
13 Fyhn TJ, Knatten CK, Edwin B, Schistad O, Aabakken L, Kjosbakken H, Pripp AH, Emblem R, Bjørnland K. Randomized Controlled Trial of Laparoscopic and Open Nissen Fundoplication in Children. Ann Surg. 2015; 261(6): 1061-7. (PMID: 26291953)
14 Papandria D, Goldstein SD, Salazar JH, Cox JT, McIltrot K, Stewart FD, Arnold M, Abdullah F, Colombani P. A randomized trial of laparoscopic versus open Nissen fundoplication in children under two years of age. J Pediatr Surg. 2015; 50(2): 267-71. (PMID: 25638616)
15 Fox D, Morrato E, Campagna EJ, Rees DI, Dickinson LM, Partrick DA, Kempe A. Outcomes of laparoscopic versus open fundoplication in children's hospitals: 2005-2008. Pediatrics. 2011; 127(5): 872-80. (PMID: 21502226)
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16 Ruiz-Tovar J, Diez-Tabernilla M, Chames A, Morales V, Martinez-Molina E. Clinical outcome at 10 years after laparoscopic versus open Nissen fundoplication. J Laparoendosc Adv Surg Tech A. 2010; 20(1): 21-3. (PMID: 19916741)
17 Thatch KA, Yoo EY, Arthur LG 3rd, Finck C, Katz D, Moront M, Prasad R, Vinocur C, Schwartz MZ. A comparison of laparoscopic and open Nissen fundoplication and gastrostomy placement in the neonatal intensive care unit population. J Pediatr Surg. 2010; 45(2): 346-9. (PMID: 20152349)
18 Knatten CK, Hviid CH, Pripp AH, Emblem R, Bjørnland K. Inflammatory response after open and laparoscopic Nissen fundoplication in children: a randomized study. Pediatr Surg Int. 2014; 30(1): 11-7. (PMID: 24240577)
19 Pacilli M, Eaton S, McHoney M, Kiely EM, Drake DP, Curry JI, Lindley KJ, Pierro A. Four year follow-up of a randomised controlled trial comparing open and laparoscopic Nissen fundoplication in children. Arch Dis Child. 2014; 99(6): 516-21. (PMID: 24532685)
20 Salminen P, Hurme S, Ovaska J. Fifteen-year outcome of laparoscopic and open Nissen fundoplication: a randomized clinical trial. Ann Thorac Surg. 2012; 93(1): 228-33. (PMID: 22098922)
21 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; 250(5): 698-706. (PMID: 19801931)
22 Ackroyd R, Watson DI, Majeed AW, Troy G, Treacy PJ, Stoddard CJ. Randomized clinical trial of laparoscopic versus open fundoplication for gastro-oesophageal reflux disease. Br J Surg. 2004 Aug;91(8):975-82. (PMID: 15286957)
23 Draaisma WA, Buskens E, Bais JE, Simmermacher RK, Rijnhart-de Jong HG, Broeders IA, Gooszen HG. Randomized clinical trial and follow-up study of cost-effectiveness of laparoscopic versus conventional Nissen fundoplication. Br J Surg. 2006 Jun;93(6):690-7. (PMID: 16671071)
24 Blomqvist AM, Lönroth H, Dalenbäck J, Lundell L. Laparoscopic or open fundoplication? A complete cost analysis. Surg Endosc. 1998; 12(10): 1209-12. (PMID: 9745058)
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