Laparoscopic sleeve gastrectomy and gastroesophageal reflux disease: a systematic review and meta-analysis

Accepted Manuscript Laparoscopic Sleeve Gastrectomy and Gastroesophageal Reflux Disease: a Systematic Review and Meta-Analysis J.E. Oor, D.J. Roks, Ç. Unlu, E.J. Hazebroek PII:

S0002-9610(15)00422-5

DOI:

10.1016/j.amjsurg.2015.05.031

Reference:

AJS 11614

To appear in:

The American Journal of Surgery

Received Date: 30 April 2015 Accepted Date: 17 May 2015

Please cite this article as: Oor JE, Roks DJ, Unlu Ç, Hazebroek EJ, Laparoscopic Sleeve Gastrectomy and Gastroesophageal Reflux Disease: a Systematic Review and Meta-Analysis, The American Journal of Surgery (2015), doi: 10.1016/j.amjsurg.2015.05.031. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Laparoscopic Sleeve Gastrectomy and Gastroesophageal Reflux Disease: a Systematic Review and Meta-Analysis

J.E. Oor1, D.J. Roks2, Ç. Unlu1, E.J. Hazebroek1 1

RI PT

Running head: Sleeve Gastrectomy and Reflux

Department of Surgery, St. Antonius Hospital, Koekoekslaan 1, 3430VB Nieuwegein, The Nether-

lands; 2Department of Surgery, Meander Medical Center, Maatweg 3, 3813 TZ Amersfoort, The Neth-

TE D

M AN U

SC

erlands

CORRESPONDING AUTHOR:

EP

J.E. Oor, M.D.

St. Antonius Hospital Nieuwegein

AC C

Department of Surgery Koekoekslaan 1

3430 VB Nieuwegein The Netherlands

Telephone: +31(0)883201925 Fax: +31(0)306036578 Email: [email protected]

1

ACCEPTED MANUSCRIPT Abstract BACKGROUND: The effect of sleeve gastrectomy (SG) on the prevalence of GERD remains unclear. We aimed to outline the currently available literature. DATA SOURCES: All relevant databases were searched for publications examining the ef-

RI PT

fect of laparoscopic SG on GERD. Primary outcome measure was change in prevalence of GERD symptoms, anti-reflux medication use and esophageal function tests. Secondary outcomes were prevalence of new-onset GERD and esophagitis. Thirty-three articles were in-

SC

cluded. Eleven studies used questionnaires to assess changes in prevalence of GERD symptoms, with a risk difference in prevalence of 4.3%. Eight studies used esophageal function

M AN U

tests, with paradoxical results. Pooled incidence of new-onset GERD symptoms was 20%, with a strong suggestion of heterogeneity. New-onset esophagitis ranged from 6.3 to 63.3%. CONCLUSIONS: Due to high heterogeneity among available studies and paradoxical outcomes of objective esophageal function tests, the exact effect of laparoscopic SG on the prev-

TE D

alence of GERD remains unanswered. Surgeons should carefully evaluate pre-operative

Keywords:

EP

GERD symptoms when choosing the proper bariatric technique.

AC C

Gastroesophageal reflux disease, laparoscopic gastric sleeve, sleeve gastrectomy; GERD

2

ACCEPTED MANUSCRIPT Introduction Gastroesophageal reflux disease (GERD) has been shown to have a significant impact on the quality of life of patients suffering from this chronic disease of the upper digestive tract.1 GERD is a frequently encountered problem in Western populations, with a reported preva-

RI PT

lence of 10- 20 % in the general population and an increase in prevalence of 4% each year for the past two decades.2,3 Obese patients show a significant higher prevalence of GERD, ranging from 37 to 72%, thereby making GERD a potential public health problem.4,5 Through a

SC

cross-sectional study using questionnaires and endoscopy, El-Serag et al. concluded that increased BMI increases the risk of GERD symptoms and erosive esophagitis (EE), independ-

M AN U

ent of demographic features and dietary intake.6 Edelstein et al. showed central adiposity to be associated with the development of Barrett’s esophagus and a subsequent increased odds ratio was found for the development of esophageal adenocarcinoma in obese individuals.7,8 The possible pathological mechanisms involved in the higher prevalence of GERD in this group of

TE D

patients includes increased intra-abdominal pressure causing disruption of the esophagogastric junction, a hypotensive lower esophageal sphincter (LES), an increase in intragastric pressure and esophageal motor disorders.9-13

EP

Several studies showed good results after laparoscopic Roux-en-Y gastric bypass (LRYGB) procedures on GERD symptoms in (morbidly) obese patients and conclude that it is a safe

AC C

procedure for inducing weight-loss in morbidly obese adolescents as well as treating the concomitant gastro-intestinal co-morbidities, including GERD.14-18 Sleeve gastrectomy (SG) was first introduced in 1988 by Hess as part of the biliopancreatic diversion duodenal switch (BPD-DS) procedure. In 1999 it was first performed laparoscopically and has gradually become a stand-alone bariatric procedure.19,20 Laparoscopic SG is a bariatric procedure that is fast gaining popularity worldwide for treating (morbidly) obese patients due to being a relatively technically simple and fast procedure compared to LRYGB.

3

ACCEPTED MANUSCRIPT SG acts in a different way compared to LRYGB, since it uses restriction of the stomach size to induce satiety and decreases appetite through resection of ghrelin-producing cells, thereby inducing weight-loss and improvement of obesity-related comorbidities.21,22 However, there still remains controversy about the exact effect of SG on postoperative GERD symptoms. In a

RI PT

previous systematic review in 2011, Chiu et al. found differing outcomes among the studies analyzing GERD and SG, and conclude that the evidence of the effect of SG on GERD did not consolidate to a consensus.23 In the past three years, multiple retrospective and prospec-

SC

tive studies have reported on the influence of laparoscopic SG on GERD, including studies using objective esophageal function tests. The aim of the present review is to evaluate the

M AN U

effect of laparoscopic SG on postoperative GERD symptoms in (morbidly) obese patients by

AC C

EP

TE D

systematically reviewing the current available literature concerning this important topic.

4

ACCEPTED MANUSCRIPT Materials and Methods Literature search Two authors (JO and DR) independently performed a literature search to identify studies investigating GERD in obese patients undergoing LSG with a BMI of more than 35. Both au-

RI PT

thors were experienced with performing systematic reviews and meta-analyses. MEDLINE databases were searched for papers published between November 2005 and November 2014, using the following keywords: ("sleeve gastrectomy AND ("Gastroesophageal reflux”

SC

(Mesh)). Free text words, including sleeve gastrectomy or gastric sleeve, were also used instead of Mesh terms to avoid missing recent articles that had not yet been given a Mesh label.

M AN U

EMBASE database was searched with the following terms: Sleeve Gastrectomy and Gastroesophageal Reflux. CINAHL database was also checked for relevant studies with the following keywords: (“sleeve gastrectomy” AND “gastroesophageal reflux disease”). The Cochrane database of Systematic Reviews was searched with the following words: “sleeve

TE D

gastrectomy” AND “gastroesophageal reflux disease”. The search was not restricted to any language, but in the systematic review, only studies published in English were taken into ac-

EP

count.

Validity assessment

AC C

After identifying relevant titles, all abstracts were read and eligible articles were retrieved. A manual cross-reference search of the references of relevant articles was performed to identify other studies not found in the search. Only studies published in English were included. No unpublished data were included. A full search strategy is available at request. Two authors independently assessed the methodological quality of the articles using the checklist of the Cochrane collaboration and MINORS quality score, with a global ideal score of 16 for noncomparative studies and 24 for comparative studies.24

5

ACCEPTED MANUSCRIPT Definition GERD is defined as the condition developing when reflux of stomach contents causes the characteristic symptoms retrosternal burning (heartburn) and regurgitation. Recalcitrant GERD concerns GERD-symptoms not adequately responding to medical therapy. GERD-

RI PT

symptoms can be diagnosed through patient symptom reporting, chart review or standardized questionnaires. A patient was considered “obese” and “morbidly obese” if the patient had a BMI of more than 30 and more than 35 respectively. LSG is defined as the (stand alone) lapa-

SC

roscopic surgical technique in which the stomach is vertically divided, leading to an average

Inclusion and exclusion criteria Types of studies

M AN U

reduction of stomach size of approximately 25% of the original size.

Articles were eligible for inclusion if the following criteria were met: publications dealing

TE D

with patients undergoing laparoscopic SG, publications describing pre- and postoperative GERD-symptoms and/or esophageal function tests, articles in English, human studies and available full text. The following exclusion criteria were used for study selection: abstracts,

EP

case-series, articles describing laparoscopic SG after prior fundoplication, laparoscopic SG with concomitant anti-reflux procedures, laparoscopic SG following previous surgical bari-

AC C

atric procedures, open sleeve gastrectomy and non-English articles.

Types of participants

Obese and morbidly obese patients (BMI > 30 and BMI > 35 respectively) undergoing laparoscopic SG.

Types of bariatric surgical procedure

6

ACCEPTED MANUSCRIPT Only articles reporting the prevalence of GERD symptoms, the use of anti-reflux medication and/or outcome of esophageal function tests before and after laparoscopic SG were included.

Types of outcome measures

RI PT

Primary outcome was the difference in prevalence of GERD following laparoscopic SG, reported through either changes in reported GERD symptoms, changes in the use of anti-reflux medication or by changes in outcome of esophageal function tests. Secondary outcomes were

SC

pre- and postoperative prevalence of esophagitis and the incidence of new-onset esophagitis and new-onset GERD. If an article only mentioned the number or percentage of patients with

M AN U

postoperative improvement and remission of GERD-symptoms, we considered the postoperative prevalence to consist of the number / percentage of patients with pre-operative GERDsymptoms minus the number / percentage of patients with complete remission of GERD-

Data analysis

TE D

symptoms.

MetaAnalysist software version 3.1 was used for the meta-analysis. To provide a reliable out-

EP

come, and to gain sufficient homogeneity of the pooled data only 2 or more randomized controlled clinical trials (RCT) or 5 or prospective / retrospective comparable studies were used

AC C

for pooled analyses. Therefore, for the primary outcome, only studies using (validated) questionnaires for the pre- and postoperative evaluation of GERD symptoms were used. For studies reporting on the outcome of esophageal function test, only 5 or more studies providing functional outcome of patients were pooled. In order to gain sufficient studies for the secondary outcome, only 5 or more studies using either validated questionnaires or oesophageal function tests were pooled. Rates were pooled using a random-effects model. If a study reported mean and standard deviation (SD) for two subgroups within the same study, pooled

7

ACCEPTED MANUSCRIPT mean and SD were calculated by using the variance. We determined the presence of heterogeneity between the studies by using a forest plot and by performing a

("chi-squared") het-

AC C

EP

TE D

M AN U

SC

RI PT

erogeneity test and the I2–index was calculated.

8

ACCEPTED MANUSCRIPT Results Description of studies The flowchart for the systematic review is shown in Figure 1. A total of 385 publications were initially identified in the literature search, from which 226 articles were screened based

RI PT

upon the title or abstract. In total, 65 articles were retrieved for more detailed information. Electronic links to related articles and references of selected articles were hand searched as well. Duplicate publications and papers that reported on (parts of) the same study population

SC

were excluded from the study. After reading the retrieved articles and the application of our inclusion criteria, we found 33 relevant articles.25-57 There was complete agreement among

M AN U

the authors as to the inclusion of these studies.

Included studies

The included studies describe a total of 8092 obese patients undergoing laparoscopic SG. Fif-

TE D

teen studies reported pre-operative comorbid conditions, consisting of the typical obesityrelated comorbidities hypertension, type 2 diabetes, dyslipidemia and sleep apnea. The mean pre-operative BMI ranged from 36 kg/m2 to 60 kg/m2 , with each individual study demonstrat-

EP

ing a wide range of reported BMI among patients. The excess weight loss (EWL) among the included studies ranged from 19% to 83.3%, with follow-up ranging from 1 to 60 months. Of

AC C

the included 33 studies, 30 studies report the effect of laparoscopic SG on the prevalence of GERD symptoms, 4 studies report differences in the use of anti-reflux medication and 8 studies present data of esophageal function tests.

Of the included studies reporting on the difference in prevalence of GERD symptoms, 12 report a decrease in the postoperative prevalence of GERD-symptoms, whereas 16 studies reported an increase. The relative difference in prevalence of GERD-symptoms ranged from a

9

ACCEPTED MANUSCRIPT relative decrease of 97% to an increase of 300% following surgery. The results are summarized in Table 1.25-57 The results of studies describing changes in anti-reflux medication use and outcome of esophageal function tests are summarized in Table 2-5. All studies were of

Studies using questionnaires for assessing prevalence of GERD

RI PT

moderate quality using the MINORS scoring scale (Table 6).

A total of 11 studies using standardized questionnaires to monitor pre- and postoperative

SC

prevalence of GERD-symptoms were identified, containing a total of 641 patients. Howard et al. used symptom reporting and validated questionnaires pre- and postoperative and found a

M AN U

relative increase in GERD symptoms of 57.1%.33 Both Braghetto et al. and Tai et al. used preand postoperative questionnaires and endoscopy and found an increase in the prevalence of GERD-symptoms of 27.5% and 34.9%, respectively.26,38 Burgerhart et al. and Gorodner et al. used questionnaires, pH-metry and manometry and found an increase in prevalence of 20%

TE D

and 7%, respectively (table 3-5).29,32 Carabotti et al. and Mohos et al. only used questionnaires pre- and postoperatively and found a decrease in prevalence of 1.3% and 12.7% respectively.43,51 Santonicola et al. and Sharma et al. used questionnaires, endoscopy and scintigra-

EP

phy and found a decrease of the prevalence of GERD-symptoms of 19.6% and 15.6%, respectively.55,56 Moon et al. found an increase in reported GERD symptoms of 11.8% following

AC C

laparoscopic SG.37 Rebecchi et al. used questionnaires, endoscopy, manometry and 24-hr pHmetry (table 3 and 4) and found a relative decrease of 56% in reported symptoms.54 Because of the high number of studies using validated questionnaires and their relative comparability due to the use of standardized questionnaires, data were pooled. For the difference in prevalence of GERD before and after laparoscopic SG, a pooled risk difference of 4.3 % was found. There was a strong suggestion of heterogeneity among these studies (I2=89 %)(Figure 2).

10

ACCEPTED MANUSCRIPT

New-onset GERD-symptoms New-onset GERD symptoms is presented as a percentage of the total group of patients undergoing laparoscopic SG (Table 1). A total of 24 studies reported the incidence of new-onset

RI PT

GERD symptoms or the percentage of new-onset GERD could be calculated, with an incidence ranging from 0 % to 34.9% and follow-up varying between 1 and 60 months. Seven studies reporting the incidence of new-onset GERD symptoms using (standardized) question-

SC

naires could be pooled.28,29,32,33,38,43,54 The pooled incidence of new-onset GERD symptoms for these patients was 20%. There was a strong suggestion of heterogeneity among these stud-

M AN U

ies (I2=68 %)(Figure 3).

New-onset esophagitis

Four studies reported the incidence of new-onset esophagitis, ranging from 6.3% to

TE D

63.3%.27,38,54,56 All 4 studies used pre- and postoperative questionnaires and endoscopy to monitor esophagitis, with the study performed by Braghetto et al. not reporting the follow-up period and 12 months of follow-up in the study of Tai et al., Sharma et al. and Rebecchi et al..

AC C

pooled.

Due to the limited number of studies reporting new-onset EE, data could not be

EP

27,38,54,56

Changes in the use of anti-reflux medication Four of the included studies reported on the effect of laparoscopic SG on the use of anti-reflux medication (table 2).31,42,39,54 Catheline et al. analysed the resolution of co-morbidities among 45 patients who had undergone a primary SG, with a total follow-up of 5 years.31 With a mean EWL of 60% at 5 year follow-up, a 200% increase of patients requiring PPI therapy was found.31 Zhang et al. compared the resolution of co-morbidities between patients under-

11

ACCEPTED MANUSCRIPT going laparoscopic SG and LRYGB with a follow-up of 1 year.42 No significant difference between pre- and postoperative use of anti-reflux medication was found. Sheppard et al. found a significant increase in PPI use in patients following SG compared to LRYGB at 1 month to 2 years postoperative, with a peak at 6 months.39 Rebecchi et al. prospectively ana-

RI PT

lysed 71 patients undergoing laparoscopic SG, of who 65 were included.54 At 24 months of

pooled.

Included studies reporting on 24-hr pH results

SC

follow-up, a decrease of 71% of patients requiring PPI therapy was found.54 Data could not be

M AN U

Three studies reported data following 24-hr pH measuring as an objective instrument for determining the effect of LSG on the prevalence of GERD (table 3).29,32,54 With a follow-up of 3 and 12 months after laparoscopic SG, Burgerhart et al. and Gorodner et al. found an increase in total acid exposure of 193% and 102% respectively.29,32 Furthermore, an increase in the

TE D

DeMeester score of 125% was found, together with 36% of the patients demonstrating “denovo” pathologic 24-hr pH-results at 12 months follow-up.32 Rebecchi et al. included 28 patients with pre-operative pathologic esophageal acid exposure and 37 patients with normal pH-

EP

results.54 Within the pathologic group and the normal group, a postoperative decrease in total esophageal acid exposure of 58.8% and an increase of 9.4% respectively were found. “De

AC C

novo” pathologic pH-results were found in 10.8% of the patients with normal esophageal acid exposure prior to surgery.54 Data could not be pooled.

Included studies reporting on manometry results Seven studies describe manometric changes in patients following LSG (table 4).27,29,32,47,49,52,54 Three studies report a significant decrease in lower esophageal resting pressure (LESP) ranging from 26.1 to 39.9% with a follow-up ranging from 3 to 12 months following laparoscopic

12

ACCEPTED MANUSCRIPT SG. Within both their two subgroups of patients, Rebecchi et al. found no significant difference in pre- and postoperative LESP.54 Paradoxically, Petersen et al. found a significant increase of LESP of 118% and 153% at 6 days and 8 months following laparoscopic SG, respectively.52 Kleidi et al. also report a significant increase in LESP of 12% at 1.5 month of

RI PT

follow-up.49 A significant increase in ineffective esophageal motility was only found by Del Genio et al..47 Lower esophageal sphincter length only significantly changed in the study of

SC

Kleidi et al., with an increase of 37.5% at 1.5 month follow up.49 Data could not be pooled.

Included studies reporting on combined pH-Impedance results

measurements (table 5).

29,47

M AN U

In 2 studies, the effect of LSG on GERD was determined using combined pH-Impedance Only Del Genio et al. found a significant change in the total

number of reflux episodes, with a reported increase of 60% at 13 months following LSG.47

Excluded studies

TE D

Data could not be pooled.

AC C

EP

The excluded studies are summarized in Table 7.58-89

13

ACCEPTED MANUSCRIPT Discussion Since the introduction of SG as a stand alone bariatric procedure, the exact effect of SG on GERD symptoms remains controversial. In 2011, Chiu et al. performed a systematic review on this topic, and concluded that there was too much heterogeneity of the included studies and

RI PT

a proper conclusion concerning the effect of laparoscopic SG on (pre-operative) GERD symptoms could not be made.23 Since then, many studies, including those with a prospective design, (standardized) questionnaires and objective esophageal function tests, have tried to deal

SC

with this problem in recent years. Of the 33 included studies in this review, a total of 16 studies report an increase of GERD symptoms following LSG.25-27,29-41 These studies include both

M AN U

prospective studies using (standardized) questionnaires and objective function tests as well as retrospective analysis based on chart reviews. A total of 12 studies report a decrease in the prevalence of GERD symptoms following laparoscopic SG.43-46,48,50,51,53-57 When performing a meta-analysis of the included studies describing the difference in reported prevalence of

TE D

GERD-symptoms through standardized questionnaires that are eligible for pooling, this suspected heterogeneity was confirmed by a high I2-value (figure 3). We can only state, based upon the performed meta-analysis, that there appears to be a minimal trend towards an in-

EP

creased prevalence of GERD symptoms following laparoscopic SG among the pooled studies,

AC C

without any statistical difference.

One can advocate that the presence of GERD symptoms does not necessarily mean a patient is indeed suffering from GERD, but instead suffers from other conditions such as functional heartburn. Therefore, 24-hr pH measuring remains the ‘golden standard’ for the diagnosis of GERD. Taking this into account, together with the high suspicion of heterogeneity among the included studies reporting on the changes in prevalence of GERD symptoms alone, we analysed changes in the use of anti-reflux medication and changes in outcome of esophageal function tests to further determine the influence of laparoscopic SG on GERD. The effect of

14

ACCEPTED MANUSCRIPT SG on objective esophageal function tests have not been previously described in a systematic review.

RI PT

Changes in the use of anti-reflux medication Concerning the changes in the use of anti-reflux medication before and after laparoscopic SG, the reported data are paradoxical. Whereas Sheppard et al. and Catheline et al. report a sub-

SC

stantial increase in the use of anti-reflux medication at 6 and 60 months of follow-up respectively, Rebecchi et al. found a significant decrease.39,31,54 Since the usage of anti-reflux medi-

M AN U

cation by patients not necessarily means a patient is indeed suffering from GERD, and so PPIusage correlates poorly with the presence of objectified GERD, esophageal function tests pro-

Changes 24-hr pH results

TE D

vide the most objective answer to the influence of LSG on GERD in our opinion.

There appear to be controversial results regarding the effect of laparoscopic SG on total acid

EP

exposure and DeMeester score. Burgerhart et al. and Gorodner et al. report a significant in-

AC C

crease in total acid exposure at 3 and 12 months follow-up respectively, while Rebecchi et al. find a significant decrease in total acid exposure within the group of patients with pathologic pre-operative 24-hr pH results at 24 months follow-up.29,32,54 A possible explanation for these paradoxical results could be the difference in follow-up, in which a long-term follow-up is associated with a relative higher EWL, although the reported EWL by Gorodner et al. is even higher than the EWL reported by Rebecchi et al.32,54 Furthermore, a lack of a standardized technique for SG may be responsible for these differences. This also includes the use of concomitant hiatal hernia repair. Rebecchi et al. excluded all patients with large hiatal hernia’s,

15

ACCEPTED MANUSCRIPT whereas as Gorodner et al. and Burgerhart et al. did not, which might have influenced the outcomes. These possible explanations also account for the difference in change of DeMeester score between Gorodner et al. and Rebecchi et al.. Concerning the influence of bougie size, Rebecchi et al. and Gorordner both used a 36 Fr bougie, whereas Burgerhart et al. used a 34Fr

RI PT

bougie.54,32,29

SC

Manometric changes

Only Del Genio et al. report on changes in esophageal motility following laparoscopic SG and

M AN U

found a significant increase of ineffective esophageal motility at 13 months follow-up.47 Concerning changes in lower esophageal sphincter pressure (LESP), controversial data are presented by the included studies, with 3 studies reporting a significant decrease in LESP, 2 studies reporting a significant increase and 2 studies reporting no significant changes in LESP

TE D

following laparoscopic SG. The most frequently mentioned explanation for changes in LESP following laparoscopic SG concerns the performed surgical technique. Braghetto et al. correlated their significant decrease of LESP with partial section of the cardia.27 The only signifi-

EP

cant change in LES length is reported by Kleidi et al., who found a significant increase at 1.5

AC C

months follow-up.49

Combined pH-Impedance

Only Burgerhart et al. and Del Genio et al. used combined pH-Impedance studies at 3 and 13 months following laparoscopic SG respectively.29,47 Only Del Genio et al. found a significant increase in total reflux episodes following surgery, most likely to be caused by stasis and

16

ACCEPTED MANUSCRIPT postprandial regurgitation, which is again caused by changes in esophageal motility and increased gastric pressure.47

Proposed responsible mechanisms

RI PT

When performing this systematic review, the following possible mechanisms responsible for an increase in postoperative prevalence of GERD were mentioned. Both Braghetto et al. and Gorodner. et al. demonstrated a decline of lower esophageal sphincter pressure (LESP) and

SC

consider this to be an important factor contributing to the development of GERD.27,32 Burgerhart et al. used pre- and postoperative 24-h pH/impedance monitoring and esophageal ma-

M AN U

nometry, as well as a validated questionnaire and found that GERD symptoms did not significantly change following laparoscopic SG, but other gastrointestinal symptoms increased [29]. Furthermore, esophageal acid exposure significantly increased and the distal contractile integral as well as the LESP significantly decreased. They hypothesize that disruption of the an-

TE D

gle of His as well as the development of new hiatal hernias with subsequent migration of the proximal sleeve above the level of the hiatus following laparoscopic SG could explain newonset GERD.29 Himpens et al. also suggest that removal of the angle of His and a subsequent

EP

decline in gastric compliance potentially causes increased reflux.71 The fact that this increase

AC C

in GERD would slowly start to decrease again at 3 years following surgery would be explained by a subsequent increase in gastric compliance.70 Furthermore, they state that another important cause of both postoperative GERD and weight regain is ‘neofundus’ formation. A ‘neofundus’ develops when there is to much fundus left due to stapling away from the left crus, causing a sleeve-tube with a conical shape. This could potentially cause proximal dilatation and ‘neofundus’ formation70. Hamoui et al. also accounted the altered anatomy of the angle of His as the potential cause of increased reflux following laparoscopic SG and recommend to be cautious when offering SG to patients with pre-operative GERD.69 Braghetto et al.

17

ACCEPTED MANUSCRIPT state that GERD following LSG is secondary to either the development of high intra-gastric pressure following laparoscopic SG or due to disruption of the sling fibres responsible for the competency of EGJ, during dissection around the angle of His.27 The following mechanisms are stated to potentially cause a decrease in postoperative GERD symptoms. Petersen et al.

RI PT

found that laparoscopic SG significantly increases LESP independently of weight loss and conclude that this may protect patients from gastroesophageal reflux.52 Del Genio et al. conclude that LSG creates delayed esophageal emptying without impairing LES function and

SC

state that a correctly fashioned sleeve does not induce de novo GERD, with the increased acid

M AN U

exposure most likely to be caused by stasis and postprandial regurgitation.47

New-onset GERD

A total of 24studies reported the incidence of new-onset GERD symptoms or the incidence

TE D

could be calculated, with incidence ranging from 0 % to 34.9%. Despite the high amount of heterogeneity among the included studies and a large variation in terms of follow-up, we can conclude that SG could induce serious GERD symptoms among patients without pre-

EP

operative GERD complaints. This is further supported by two included studies providing data on changes in 24-hr pH results following laparoscopic SG (table 3). Both Gorodner et al. and

AC C

Rebecchi et al. report on the development of ‘de novo’ pathologic pH-results in 36% and 10.5% of the patients respectively.32,54

Role of concomitant hiatal hernia repair We included studies reporting on laparoscopic SG with concomitant hiatal hernia repair (HHR). However, in most included studies, patients suffering from a large HH were excluded, or data on the presence of HH is missing. A number of studies reporting on laparoscopic SG

18

ACCEPTED MANUSCRIPT with concomitant HHR were excluded based upon our previous stated exclusion criteria (table 7). Sheppard et al. report that 15% of their 378 patients were found to have a significant hiatal hernia requiring repair.39 They report that there were no significant differences in reflux rates between patients with and without a HH, and no differences between those who had their HH

RI PT

repaired during surgery compared to does who did not.39 Daes et al. report that of the 137 patients treated with laparoscopic SG, 25.3% was diagnosed with a HH, of which 85.3% patients reported pre-operative GERD symptoms.46 At 6-12 months follow-up, 2 patients report-

SC

ed persistent GERD symptoms, with both patients suffering from a large HH pre-operatively. No patient with small or no HH reported postoperative GERD symptoms. The authors con-

M AN U

clude that with careful attention to the technical aspects of SG, including HH repair and the proper angle under which to staple the sleeve, significantly reduced occurrence of GERD symptoms can be achieved.46 Soricelli et al. compared patients undergoing SGH with patients undergoing SG and HHR.87 Of the patients diagnosed with a HH, 42% reported pre-operative

TE D

GERD symptoms, which disappeared in more than 80% of them at a mean follow-up of 18 months. De novo GERD symptoms developed in 22.9% of the patients treated with SG alone, compared to 0% in the patients treated with SH and HHR.87 Santonicola et al. however, report

EP

that laparoscopic SG with concomitant HHR in patients with HH did not led to an improvement in GERD symptoms, and even resulted in a higher heartburn frequency-intensity scores This is the only study not supporting positive results of HHR in terms of GERD control . In

AC C

55

their systematic review, in which case series and case reports were also included, Mahawar et al. conclude that concomitant HHR is a safe procedure and can be recommended as an acceptable management strategy for obese patients with hiatus hernia, providing acceptable postoperative GORD rates.90 Of all participants in the International Sleeve Gastrectomy Expert Panel, 83% of participants agreed on an aggressive approach to identify and subsequently repair intra-operatively diagnosed HH when performing laparoscopic SG and consider HH a

19

ACCEPTED MANUSCRIPT relative contraindication to laparoscopic SG unless repaired adequately.91 Concomitant hiatal repair is challenging, since loose approximation of the hiatus predisposes to migration of the sleeve, whereas tight approximation predisposes to stenosis and dysphagia. Although the above mentioned studies overall indeed support the positive effect of concomitant HHR, fur-

RI PT

ther randomized controlled trials comparing different techniques and providing long-term follow-up, as well as standardisation of the technique of both laparoscopic SG and HHR are

SC

necessary to provide adequate information regarding the additional effect of HHR on GERD.

M AN U

Role of bougie-size

All included studies except for one reported the size of the bougie used during surgery, with a bougie-size ranging from 26.4 Fr to 50 Fr. This illustrates the current lack of standardisation of the laparoscopic SG among the included studies, thereby contributing to the heterogeneity

TE D

among the studies. One could hypothesize that using a small-sized bougie leads to disruption of a relative larger portion of the angle of His and a relative higher intragastric pressure, thereby potentially causing (new-onset) GERD symptoms. On the other hand, using a larger

EP

bougie-size can cause weight regain and GERD symptoms due to an increased number of residual parietal cells [110]. Due to a relatively small amount of studies using objective

AC C

esophageal function tests, no conclusions regarding the association between bougie size and gastroesophageal function can be made.

LSG with anti-reflux procedure Only one study performed an additional anti-reflux procedure. Santoro et al. selected obese patients with pre-operative GERD.84 In addition to a laparoscopic SG they also performed an anti-reflux procedure, consisting of hiatoplasty and cardioplication. They conclude that this

20

ACCEPTED MANUSCRIPT did not ad any morbidity nor influence weight loss, but that it does lead to a significant reduction in the occurrence of GERD symptoms compared to laparoscopic SG alone, with a mean follow-up of 22 months.84

RI PT

Study limitations

This review carries certain limitations. First, the included studies report a wide variability in

SC

results. Our meta-analysis of changes in reported GERD symptoms showed substantial heterogeneity among the included studies, making it impossible to make definitive conclusions

M AN U

regarding the exact effect of laparoscopic SG. Despite the fact that there is substantial heterogeneity, we can state that there appears to be a slight trend towards an increase in prevalence after laparoscopic SG. This also accounts for the incidence of new-onset GERD, with a pooled incidence of 20%, but again with substantial heterogeneity among the included stud-

TE D

ies. Overall, the quality of the included studies was moderate, mainly due to a relative lack of prospectively based studies and the use of symptom reporting and retrospective chart analysis instead of standardized questionnaires. Since 24-hr pH-measuring is considered the ‘gold

EP

standard’ test for diagnosing GERD, we analysed esophageal function tests to examine the effect of laparoscopic SG on GERD, which have not been previously included in a systematic

AC C

review. However, the included studies provided paradoxically results and data could not be pooled. An important explanation for the wide variability of the included studies is the lack of a standardized technique of laparoscopic SG. Multiple authors postulate the possible negative effect of laparoscopic SG on the angle of His. The difference among different surgeons concerning the angle under which the sleeve is being stapled could thereby possible explain the wide variability in the reported prevalence of postoperative GERD symptoms and paradoxical outcomes of esophageal function tests. This also accounts for the use of concomitant HHR. Furthermore, follow-up ranged from 1 month to 60 months, which might influence the

21

ACCEPTED MANUSCRIPT reported prevalence of GERD, since it has been shown that this is related to BMI. Another possible explanation is the wide variability in reported BMI among the patients who underwent laparoscopic SG, since this will not only influence the pre-operative prevalence of GERD, but performing a laparoscopic SG in a patient with a BMI of 60 kg/m2 will be techni-

RI PT

cally more challenging compared to a patient with a BMI of 40 kg/m2, thereby potentially

AC C

EP

TE D

M AN U

SC

affecting the performed technique.

22

ACCEPTED MANUSCRIPT Conclusion Through this systematic review and meta-analysis, we can only state that there appears to be a slight trend towards an increased prevalence of GERD symptoms following LSG, but due to

RI PT

the suspected high heterogeneity of the included studies, no definitive conclusion can be made. Objective esophageal function tests, with 24-hr pH studies being the ‘gold standard’, appear to report paradoxical results, making it impossible to determine the exact effect of laparoscopic SG on the gastroesophageal function. New-onset GERD symptoms and pathologic

SC

24-hr pH results are reported however, including in studies reporting an overall decrease in

M AN U

prevalence of GERD following laparoscopic SG. Standardisation of the technique in terms of bougie size, concomitant HHR and the angle under which to staple of the fundus when performing laparoscopic SG, as well as further prospectively designed studies using both standardized questionnaires and objective esophageal function tests are needed to provide a definitive answer to this important question. Since there is a paucity of these studies, and with the

TE D

knowledge that new-onset GERD symptoms are a relatively frequently described phenomenon, bariatric surgeons should carefully evaluate any potential pre-operative GERD-related

EP

complaints, and take this into account when making an individual consideration in choosing the proper bariatric surgical technique. Furthermore, patients should be informed regarding

AC C

the possible GERD-related effects of laparoscopic SG, including the development of newonset GERD symptoms in the postoperative period.

Acknowledgments: none Author Disclosure: drs. J.E. Oor, drs. D.J. Roks, dr. C. Unlu and dr. E.J. Hazebroek have no conflicts of interest or financial ties to disclose.

23

ACCEPTED MANUSCRIPT Legends Table 1. Study characteristics of included studies

Table 2. Included studies reporting on changes in the use of anti-reflux medication

Table 4. Included studies reporting on manometric studies

SC

Table 5. Included studies reporting on pH-Impedance studies

RI PT

Table 3. Included studies reporting on 24-hr pH-results

Table 7. Excluded studies

TE D

Figure 1. Flow sheet literature search

M AN U

Table 6. Quality assessment

Figure 2. Forrest plot of the effect of laparoscopic SG on the prevalence of GERD symptoms

AC C

EP

Figure 3. Forrest plot of the pooled incidence of new-onset GERD symptoms

24

ACCEPTED MANUSCRIPT References 1. Wiklund I. Review of the quality of life and burden of illness in gastroesophageal reflux disease. Dig. Dis. 2004;22:108-114 2. Dent J, El-Serag HB, Wallander MA, Johansson SE. Epidemiology of gastro-oesophageal reflux

RI PT

disease: a systematic review. Gut. 2005;54:710-717 3. El-Serag HB. Time trends of gastroesophageal reflux disease: a systematic review. Clin. Gastroenterol. Hepatol. 2007;5:17-26

troesophageal reflux? Dig. Dis. Sci. 1995;40:1632-1635

SC

4. Lundell L, Ruth M, Sandberg N, Bove-Nielsen M. Does massive obesity promote abnormal gas-

2008;8:233-239

M AN U

5. Anand G, Katz PO. Gastroesophageal reflux disease and obesity. Rev. Gastroenterol. Disord.

6. El-Serag HB, Graham DY, Satia JA, Rabeneck L. Obesity is an independent risk factor for GERD symptoms and erosive esophagitis. Am. J. Gastroenterol. 2005;100:1243-1250 7. Edelstein ZR, Farrow DC, Bronner MP et al. Central adiposity and risk of Barrett's esophagus. Gas-

TE D

troenterology. 2007;133:403-411

8. Lagergren J, Bergstrom R, Nyren O. Association between body mass and adenocarcinoma of the esophagus and gastric cardia. Ann. Intern. Med. 1999;130:883-890

1987;72:1-3

EP

9. Hagen J, Deitel M, Khanna RK, Ilves R. Gastroesophageal reflux in the massively obese. Int. Surg.

AC C

10. Jaffin BW, Knoepflmacher P, Greenstein R. High prevalence of asymptomatic esophageal motility disorders among morbidly obese patients. Obes. Surg. 1999;9:390-395 11. Mercer CD, Wren SF, DaCosta LR, Beck IT. Lower esophageal sphincter pressure and gastroesophageal pressure gradients in excessively obese patients. J. Med. 1987;18:135-146 12. de Vries DR, van Herwaarden MA, Smout AJ, Samsom M. Gastroesophageal pressure gradients in gastroesophageal reflux disease: relations with hiatal hernia, body mass index, and esophageal acid exposure. Am. J. Gastroenterol. 2008;103:1349-1354

25

ACCEPTED MANUSCRIPT 13. Pandolfino JE, El-Serag HB, Zhang Q et al. Obesity: a challenge to esophagogastric junction integrity. Gastroenterology. 2006;130:639-649 14. Perry Y, Courcoulas AP, Fernando HCet al. Laparoscopic Roux-en-Y gastric bypass for recalcitrant gastroesophageal reflux disease in morbidly obese patients. JSLS. 2004;8:19-23

RI PT

15. Wittgrove AC, Clark GW, Schubert KR. Laparoscopic Gastric Bypass, Roux-en-Y: Technique and Results in 75 Patients With 3-30 Months Follow-up. Obes. Surg. 1996;6:500-504

16. Nijhawan S, Martinez T, Wittgrove AC. Laparoscopic gastric bypass for the adolescent patient: long-term results. Obes. Surg. 2012;22:1445-1449

SC

17. De Groot NL, Burgerhart JS, Van De Meeberg PC et al. Systematic review: the effects of conservative and surgical treatment for obesity on gastro-oesophageal reflux disease. Aliment. Pharmacol.

M AN U

Ther. 2009;30:1091-1102

18. Tai CM, Lee YC, Wu MS. et al. The effect of Roux-en-Y gastric bypass on gastroesophageal reflux disease in morbidly obese Chinese patients. Obes. Surg. 2009;19:565-570 19. Hess DS, Hess DW. Biliopancreatic diversion with a duodenal switch. Obes. Surg. 1998;8:267-

TE D

282

20. Gumbs AA, Gagner M, Dakin G et al. Sleeve gastrectomy for morbid obesity. Obes. Surg. 2007;17:962-969

EP

21. Abu-Jaish W, Rosenthal RJ. Sleeve gastrectomy: a new surgical approach for morbid obesity. Expert Rev. Gastroenterol. Hepatol. 2010;4:101-119

AC C

22. Langer FB, Reza Hoda MA, Bohdjalian A, et al. Sleeve gastrectomy and gastric banding: effects on plasma ghrelin levels. Obes. Surg. 2005;15:1024-1029 23. Chiu S, Birch DW, Shi X et al. Effect of sleeve gastrectomy on gastroesophageal reflux disease: a systematic review. Surg. Obes. Relat. Dis. 2011;7:510-515 24. Slim K, Nini E, Forestier D et al. Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J. Surg. 2003;73:712-716 25. Abrahim A, Sperker C, Kees-Belyus M, et al. Technique and results of single-step Laparoscopic sleeve resection: 1-Year single-centre experience. Eur. Surg. Acta Chir. Austriaca. 2012;44:23-27

26

ACCEPTED MANUSCRIPT 26. Arias E, Martinez PR, Ka Ming Li V et al. Mid-term follow-up after sleeve gastrectomy as a final approach for morbid obesity. Obes. Surg. 2009;19:544-548 27. Braghetto I, Csendes A, Korn O et al. Gastroesophageal reflux disease after sleeve gastrectomy. Surg. Laparosc. Endosc. Percutan. Tech. 2010;20:148-153

RI PT

28. Braghetto I, Lanzarini E, Korn O et al. Manometric changes of the lower esophageal sphincter after sleeve gastrectomy in obese patients. Obes Surg. 2010 Mar;20(3):357-62

29. Burgerhart JS, Schotborgh CA, Schoon EJ et al. Effect of sleeve gastrectomy on gastroesophageal reflux. Obes. Surg. 2014;24:1436-1441

SC

30. Carter PR, Leblanc KA, Hausmann MG et al. Association between gastroesophageal reflux disease and laparoscopic sleeve gastrectomy. Surg. Obes. Relat. Dis. 2011;7:569-572

M AN U

31. Catheline JM, Fysekidis M, Bachner I et al. Five-year results of sleeve gastrectomy. J. Visc Surg. 2013;150:307-312

32. Gorodner V, Buxhoeveden R, Clemente G et al. Does laparoscopic sleeve gastrectomy have any influence on gastroesophageal reflux disease? Preliminary results. Surg. Endosc. 2014

TE D

33. Howard DD, Caban AM, Cendan JC, Ben-David K. Gastroesophageal reflux after sleeve gastrectomy in morbidly obese patients. Surg. Obes. Relat. Dis. 2011;7:709-713 34. Kehagias I, Spyropoulos C, Karamanakos S, Kalfarentzos F. Efficacy of sleeve gastrectomy as

2013;9:363-369

EP

sole procedure in patients with clinically severe obesity (BMI
AC C

35. Kular KS, Manchanda N, Rutledge R. Analysis of the five-year outcomes of sleeve gastrectomy and mini gastric bypass: a report from the Indian sub-continent. Obes. Surg. 2014;24:1724-1728 36. Lakdawala MA, Bhasker A, Mulchandani D et al.Comparison between the results of laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass in the Indian population: a retrospective 1 year study. Obes. Surg. 2010;20:1-6 37. Moon RC, Teixeira AF, Jawad MA. Is preoperative manometry necessary for evaluating reflux symptoms in sleeve gastrectomy patients? Surg. Obes. Relat. Dis. 2014

27

ACCEPTED MANUSCRIPT 38. Tai CM, Huang CK. Increase in gastroesophageal reflux disease symptoms and erosive esophagitis 1 year after laparoscopic sleeve gastrectomy among obese adults. Surg. Endosc. 2013;27:3937-0133022-4. Epub 2013 May 25 39. Sheppard CE, Sadowski DC, de Gara CJ et al. Rates of Reflux Before and After Laparoscopic

RI PT

Sleeve Gastrectomy for Severe Obesity. Obes. Surg. 2014 40. Soricelli E, Iossa A, Casella G et al. Sleeve gastrectomy and crural repair in obese patients with gastroesophageal reflux disease and/or hiatal hernia. Surg. Obes. Relat. Dis. 2013;9:356-361

41. Vage V, Sande VA, Mellgren G et al. Changes in obesity-related diseases and biochemical varia-

SC

bles after laparoscopic sleeve gastrectomy: a two-year follow-up study. BMC Surg. 2014;14:8-248214-8

M AN U

42. Zhang N, Maffei A, Cerabona T et al. Reduction in obesity-related comorbidities: is gastric bypass better than sleeve gastrectomy? Surg. Endosc. 2013;27:1273-1280

43. Carabotti M, Silecchia G, Greco F et al. Impact of laparoscopic sleeve gastrectomy on upper gastrointestinal symptoms. Obes. Surg. 2013;23:1551-1557

TE D

44. Chopra A, Chao E, Etkin Y et al. Laparoscopic sleeve gastrectomy for obesity: can it be considered a definitive procedure? Surg. Endosc. 2012;26:831-837 45. Cottam D, Qureshi FG, Mattar SG et al. Laparoscopic sleeve gastrectomy as an initial weight-loss

EP

procedure for high-risk patients with morbid obesity. Surg. Endosc. 2006;20:859-863 46. Daes J, Jimenez ME, Said N, Dennis R. Improvement of gastroesophageal reflux symptoms after

AC C

standardized laparoscopic sleeve gastrectomy. Obes. Surg. 2014;24:536-540 47. Del Genio G, Tolone S, Limongelli P. et al. Sleeve gastrectomy and development of "de novo" gastroesophageal reflux. Obes. Surg. 2014;24:71-77 48. DuPree CE, Blair K, Steele SR, Martin MJ. Laparoscopic sleeve gastrectomy in patients with preexisting gastroesophageal reflux disease : a national analysis. JAMA Surg. 2014;149:328-334 49. Kleidi E, Theodorou D, Albanopoulos K et al.The effect of laparoscopic sleeve gastrectomy on the antireflux mechanism: Can it be minimized? Surg. Endosc. Interv. Tech. 2013;27:4625-4630 50. Moon Han S, Kim WW, Oh JH. Results of laparoscopic sleeve gastrectomy (LSG) at 1 year in morbidly obese Korean patients. Obes. Surg. 2005;15:1469-1475 28

ACCEPTED MANUSCRIPT 51. Mohos E, Schmaldienst E, Prager M. Quality of life parameters, weight change and improvement of co-morbidities after laparoscopic roux y gastric bypass and laparoscopic gastric sleeve resectioncomparative study. Obes. Surg. 2011;21:288-294 52. Petersen WV, Meile T, Kuper MA et al. Functional importance of laparoscopic sleeve gastrectomy

RI PT

for the lower esophageal sphincter in patients with morbid obesity. Obes. Surg. 2012;22:360-366 53. Rawlins L, Rawlins MP, Brown CC, Schumacher DL. Sleeve gastrectomy: 5-year outcomes of a single institution. Surg. Obes. Relat. Dis. 2013;9:21-25

54. Rebecchi F, Allaix ME, Giaccone C et al. Gastroesophageal reflux disease and laparoscopic sleeve

SC

gastrectomy: a physiopathologic evaluation. Ann. Surg. 2014;260:909-915

55. Santonicola A, Angrisani L, Cutolo P et al.The effect of laparoscopic sleeve gastrectomy with or

M AN U

without hiatal hernia repair on gastroesophageal reflux disease in obese patients. Surg. Obes. Relat. Dis. 2014;10:250-255

56. Sharma A, Aggarwal S, Ahuja V, Bal C. Evaluation of gastroesophageal reflux before and after sleeve gastrectomy using symptom scoring, scintigraphy, and endoscopy. Surg. Obes. Relat. Dis.

TE D

2014;10:600-605

57. Weiner RA, Weiner S, Pomhoff I et al. Laparoscopic sleeve gastrectomy - Influence of sleeve size and resected gastric volume. Obes. Surg. 2007;17:1297-1305

EP

58. Abd Ellatif ME, Abdallah E, Askar W et al. Long term predictors of success after laparoscopic sleeve gastrectomy. Int. J. Surg. 2014;12:504-508

AC C

59. Bohdjalian A, Langer FB, Shakeri-Leidenmühler S et al. Sleeve gastrectomy as sole and definitive bariatric procedure: 5-year results for weight loss and ghrelin. Obes. Surg. 2010;20:535-540 60. Braghetto I, Csendes A, Lanzarini E et al. Is laparoscopic sleeve gastrectomy an acceptable primary bariatric procedure in obese patients? Early and 5-year postoperative results. Surg. Laparosc. Endosc. Percutan. Tech. 2012;22:479-486 61. Boza C, Salinas J, Salgado N et al. Laparoscopic sleeve gastrectomy as a stand-alone procedure for morbid obesity: Report of 1,000 cases and 3-year follow-up. Obes. Surg. 2012;22:866-871 62. Clapp B. Prosthetic bioabsorbable mesh for hiatal hernia repair during sleeve gastrectomy. JSLS. 2013;17:641-644

29

ACCEPTED MANUSCRIPT 63. Cuenca-Abente F, Parra JD, Oelschlager BK. Laparoscopic sleeve gastrectomy: an alternative for recurrent paraesophageal hernias in obese patients. JSLS. 2006;10:86-89 64. Daes J, Jimenez ME, Said N et al. Laparoscopic sleeve gastrectomy: symptoms of gastroesophageal reflux can be reduced by changes in surgical technique. Obes. Surg. 2012;22:1874-79

RI PT

65. Dhahri A, Verhaeghe P, Hajji H et al. Sleeve gastrectomy: technique and results. J. Visc Surg. 2010;147:e39-46

66. Eisenberg D, Bellatorre A, Bellatorre N. Sleeve gastrectomy as a stand-alone bariatric operation for severe, morbid, and super obesity. J. Soc. Laparoendoscopic Surg. 2013;17:63-67

gle surgeon Australian practice. ANZ J. Surg. 2013

SC

67. Gibson SC, Le Page PA, Taylor CJ. Laparoscopic sleeve gastrectomy: review of 500 cases in sin-

M AN U

68. Gluck B, Movitz B, Jansma S et al. Laparoscopic sleeve gastrectomy is a safe and effective bariatric procedure for the lower BMI (35.0-43.0 kg/m2) population. Obes. Surg. 2011;21:1168-1171 69. Hamoui N, Anthone GJ, Kaufman HS, Crookes PF. Sleeve gastrectomy in the high-risk patient. Obes. Surg. 2006;16:1445-1449

TE D

70. Himpens J, Dapri G, Cadiere GB. A prospective randomized study between laparoscopic gastric banding and laparoscopic isolated sleeve gastrectomy: results after 1 and 3 years. Obes. Surg. 2006;16:1450-1456

EP

71. Himpens J, Dobbeleir J, Peeters G. Long-term results of laparoscopic sleeve gastrectomy for obesity. Ann. Surg. 2010;252:319-324

AC C

72. Kotak R, Murr M. Recurrent hiatal hernia repair after sleeve gastrectomy. Surg. Obes. Relat. Dis. 2013;9:1027-1028

73. Korwar V, Peters M, Adjepong S, Sigurdsson A. Laparoscopic hiatus hernia repair and simultaneous sleeve gastrectomy: a novel approach in the treatment of gastroesophageal reflux disease associated with morbid obesity. J. Laparoendosc. Adv. Surg. Tech. A. 2009;19:761-763 74. Lazoura O, Zacharoulis D, Triantafyllidis G et al. Symptoms of gastroesophageal reflux following laparoscopic sleeve gastrectomy are related to the final shape of the sleeve as depicted by radiology. Obes. Surg. 2011;21:295-299

30

ACCEPTED MANUSCRIPT 75. Mizrahi I, Alkurd A, Ghanem M et al. Outcomes of laparoscopic sleeve gastrectomy in patients older than 60 years. Obes. Surg. 2014;24:855-860. 76. Melissas J, Koukouraki S, Askoxylakis J et al. Sleeve gastrectomy: a restrictive procedure? Obes. Surg. 2007;17:57-62

RI PT

77. Melissas J, Daskalakis M, Koukouraki S. et al. Sleeve gastrectomy-a "food limiting" operation. Obes. Surg. 2008;18:1251-1256

78. Menenakos E, Stamou KM, Albanopoulos K, et al. Laparoscopic sleeve gastrectomy performed

follow-up of 1 year. Obes. Surg. 2010;20:276-282

SC

with intent to treat morbid obesity: A prospective single-center study of 261 patients with a median

79. Merchant AM, Cook MW, Srinivasan J et al. Comparison between laparoscopic paraesophageal

tients. Am. Surg. 2009;75:620-625

M AN U

hernia repair with sleeve gastrectomy and paraesophageal hernia repair alone in morbidly obese pa-

80. Nocca D, Krawczykowsky D, Bomans B. et al. A prospective multicenter study of 163 sleeve gastrectomies: results at 1 and 2 years. Obes. Surg. 2008;18:560-565

TE D

81. Omana JJ, Nguyen SQ, Herron D, Kini S. Comparison of comorbidity resolution and improvement between laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding. Surg. Endosc. Interv. Tech. 2010;24:2513-2517

EP

82. Pallati PK, Shaligram A, Shostrom VK et al. Improvement in gastroesophageal reflux disease symptoms after various bariatric procedures: Review of the Bariatric Outcomes Longitudinal Data-

AC C

base. Surg. Obes. Relat. Dis. 2014;10:502-507 83. Pham DV, Protyniak B, Binenbaum SJ et al. Simultaneous laparoscopic paraesophageal hernia repair and sleeve gastrectomy in the morbidly obese. Surg. Obes. Relat. Dis. 2014;10:257-261 84. Santoro S, Lacombe A, Aquino CG, Malzoni CE. Sleeve gastrectomy with anti-reflux procedures. Einstein (Sao. Paulo). 2014;12:287-294 85. Shitrit AB, Magen A, Swartzs E et al. Long-term reflux-related symptoms after bariatric surgery: comparison of sleeve gastrectomy versus laparoscopic adjustable gastric banding. Lung. 2013;191:289-293

31

ACCEPTED MANUSCRIPT 86. Sieber P, Gass M, Kern B et al. Five-year results of laparoscopic sleeve gastrectomy. Surg. Obes. Relat. Dis. 2014;10:243-249 87. Soricelli E, Casella G, Rizzello M et al. Initial experience with laparoscopic crural closure in the management of hiatal hernia in obese patients undergoing sleeve gastrectomy. Obes. Surg.

RI PT

2010;20:1149-1153 88. Varban OA, Hawasli AA, Carlin AM et al. Variation in utilization of acid-reducing medication at 1 year following bariatric surgery: results from the Michigan Bariatric Surgery Collaborative. Surg. Obes. Relat. Dis. 2014

with hiatal hernia. Surg. Obes. Relat. Dis. 2009;5:707-709

SC

89. Varela JE. Laparoscopic biomesh hiatoplasty and sleeve gastrectomy in a morbidly obese patient

M AN U

90. Mahawar KK, Carr WR, Jennings N et al. Simultaneous Sleeve Gastrectomy and Hiatus Hernia Repair: a Systematic Review. Obes. Surg. 2014

91. Rosenthal RJ, International Sleeve Gastrectomy Expert Panel, Diaz AA. International Sleeve Gastrectomy Expert Panel Consensus Statement: best practice guidelines based on experience of >12,000

AC C

EP

TE D

cases. Surg. Obes. Relat. Dis. 2012;8:8-19

32

ACCEPTED MANUSCRIPT

GERD symptoms post-LSG, n (%)

83

Symptom reporting

4 (4.8)

130

Symptom reporting

167

6. Carter et al. 2011 30 7. Catheline et al. 2013 31 8. Gorodner et al. 2014 32

176

9. Howard et al. 2011 33

28

10. Kehagias et al. 2013 34 11. Kular et al. 2014 35 12. Lakdawala et al. 2010 36

203

13. Moon et al. 2014 37

26

45 14

76 50

3 (2.1)

(I)

2.1

Questionnaire, endoscopy Manometry

0 (0)

46 (27.5)

(I)

27.5

NA

NA

NA

Questionnaire, manometry, pHImpedance Follow-up surveys, chart review Follow-up surveys, chart review Questionnaire, manometry, 24hr pH Symptom reporting, questionnaires Chart review

14 (70)

18 (90)

28.6 (I)

61 (34.6)

83 (47.2)

5 (11.1)

15 (33.3)

7 (50)

8 (57)

7 (25)

11 (39.3)

0 (0)

Retrospective chart review Symptom reporting, medication use Questionnaire, preoperative manometry

4 (5.5)

10.9

New-onset esophagitis %

FU* (months)

Excess weight -loss (%)

Bougie size (Fr)

Design

MINORS

NA

12

62

38

P

9

NA

24

67.9

40

P

13

15.5

NA

NA

32

P

9

NA

NA

6

NA

32

P

13

20

NA

3

19

34

P

11

36.1 (I)

12.6

NA

12

60.7

34

R

8

200 (I)

22.2

NA

60

50.7

34

RP

11

14.3 (I)

14

NA

12

74

36

P

12

57.1 (I)

14.3

NA

1

40

38

R

10

15 (7.4)

(I)

7.4

NA

60

57.6

32

RP

10

16 (21)

300 (I)

15.7

NA

60

51.2

37

RP

8

M AN U

20

0 (0)

TE D

20

New onset GERD (%)

13 (15.7)

Effect on GERD symptoms, relative difference (%) 225 (I)

RI PT

GERD symptoms pre-LSG, n (%)

SC

Methods

EP

1. Abrahim et al. 2012 25 2. Arias et al. 2009 26 3. Braghetto et al. 2010 27 4. Braghetto et al. 2010 28 5. Burgerhart et al. 2014 29

N

AC C

Study

3 (5)

5 (9)

66.7 (I)

4

NA

12

76.1

36

R

9

17 (65,4)

19 (73.1)

11.8 (I)

NA

NA

9

NA

NA

P

12

ACCEPTED MANUSCRIPT

66

Questionnaire, endoscopy

8 (12.1)

31 (47)

287,5 (I)

34.9

63.6

12 (median)

NA

36

P

11

15. Sheppard et al. 2014 39

378

Medication use

28.4

61

114.8 (I)

NA

NA

6

NA

50

R

12

16. Soricelli et al. 2013 40

378

60 (15.9)

76 (20.1)

26.7 (I)

15.9

NA

18

NA

48

R

12

17. Vage et al. 2014 41 18. Zhang et al. 2013 42

117

Symptom reporting, endoscopy Chart review

15 (12.8)

32 (27.4)

113.3 (I)

14.6

NA

24

NA

32

P

10

26 (13)

26 (13.2)

No difference

NA

12

NA

38-40

RP

10

19. Carabotti et al. 2013 43 20. Chopra et al. 2012 44 21. Cottam et al. 2006 45 22. Daes et al. 2012 46

74

Symptom reporting, medication use Questionnaire

20 (27)

19 (25.7)

42

P

10

185

Symptom reporting

24 (13)

17 (9.2)

69.181.3 44.8

34

R

10

126

Symptom reporting

45 (36)

38 (30)

10

134

66 (49.2)

2 (1.5)

0

0

2150 (44,5)

1807 (37,4)

60 47 37

4832

NA

NA

SC

M AN U

26. Moon Han et al. 2005 50 27. Mohos et al. 2011 51 28. Petersen et al. 2012 52

25

5 (D)

16.2

NA

29.2 (D)

3.2

NA

13 (median) 6

15.5 (D)

NA

NA

12

45

46-50

RP

97 (D)

0

NA

6-12

73.5

32

P

No difference 16 (D)

0

NA

13

56

40

P

14

4.8

NA

6

NA

NA

R

9

NA

NA

NA

1.5

NA

34

P

11

TE D

23

23. Del Genio et al 2014 47 24. DuPree et al. 2014 48

0.2

5 (8.3)

0 (0)

(D)

0

NA

12

83.3

48

P

8

Questionnaire

AC C

25. Kleidi et al. 2013 49

Symptom reporting, esophagitis Manometry, pHImpedance Symptom reporting, chart review Symptom reporting, manometry Symptom reporting

EP

200

RI PT

14. Tai et al, 2013 38

24 (51)

18 (38.3)

25 (D)

NA

NA

70

42

P

13

Questionnaire, manometry

17

NA

NA

NA

NA

38 (average) 0.3 / 8

NA

35

P

12

ACCEPTED MANUSCRIPT

53

Symptom reporting

15 (28.3)

13 (24.5)

13.3 (D)

11

NA

60

81

26.4

R

8

65

25 (38.5)

11 (16.9)

56 (D)

10

7.7

24

54-56

36

P

12

31.Santonicola et al. 2014 55

102

40 (39.2)

20 (19.6)

50 (D)

10.8

6

67.8

40

P

13

32. Sharma et al. 2014 56

32

5 (15.6)

3 (9.4)

40 (D)

33. Weiner et al. 2007 57

120

Questionnaire, medication use, endoscopy, manometry and 24hr pH Questionnaire, endoscopy, barium swallow Questionnaires (2 types), endoscopy, scintigraphy Symptom reporting

42 (35)

6 (5)

86 (D)

EP

AC C

SC

NA

NA

6.3

12

64.3

36

P

12

NA

NA

24

NA

44

P

10

M AN U

N= total number of included patients *= Follow-up Fr= French I= Increase D= Decrease NA= not answered P= prospective design R= retrospective design RP= retrospective analysis of prospectively collected data

TE D

Table 1. Study characteristics of included studies

RI PT

29. Rawlins et al. 2013 53 30. Rebecchi et al. 2014 54

ACCEPTED MANUSCRIPT

Table 2. Included studies reporting on changes in anti-reflux medication use

Post-operative medication use, n (%)

FU* (months)

Bougie size (Fr)

15 (33.3)

Effect on medication use, relative difference (%) 200 (I)

45

5 (11.1)

60

34

200

26 (13)

26 (13.2)

1.5 (I)

12

38-40

71

38 (53)

11 (15.5)

71 (D)

24

36

378

58 (28.4)

125 (61)

114,8 (I)

N= number of patients *= follow-up

AC C

EP

I= increase in medication usage following LSG D= decrease in medication usage following LSG P= prospective R= retrospective RP= retrospective analysis of prospectively collected database N/A= not answered

6

TE D

Fr= French

Design

50

MINORS

RI PT

Pre-operative medication use, n (%)

RP

11

P

10

P

12

R

12

SC

Catheline et al. 2013 31 Zhang et al. 2013 42 Rebecchi et al. 2014 54 Sheppard et al. 2014 39

N

M AN U

Study

ACCEPTED MANUSCRIPT

Table 3. Included studies reporting on 24-hr pH-results

Gorodner et al. 2014 32

14

3.8 (3.1)

Postoperative total acid exposure, mean (SD)B 7.7 (5.4)

Burgerhart et al. 2014 29 Rebechhi et al. 2014 54

20

4.1 (3.5)

12 (10.4)

37/65

3.2 (1.2)

3.5 (1.1)

28/65

10.2 (3.7)

4.2 (2.6)

Relative difference of effect (%)

Preoperative DeMeester score, mean (SD) 12.6 (10.1)

Postoperative DeMeester score, mean (SD) 28.4 (19)

193 (I) P=0.004 9.4 (I)

NA

NA

11.9 (2.1)

12 (2.3)

58.8 (D) p<0.001

39.5 (16.5)

102.6 (I) P≤0.05

A

Relative difference of effect (%)

‘de novo’ pathologic pH-results (%)

Excess weight-loss (%)

FU* (months)

Bougie size (Fr)

125,4 (I) p≤0.05

36

74

12

36

NA

NA

19

3

34

0.8 (I)

10.8

56

24

36

73.2 (D)

NA

54

24

36

RI PT

Pre-operative total acid exposure, mean (SD)A

SC

N

M AN U

Study

10.6 (5.8)

= pre-operative pathologic results from 24-hr pH-study, defined as the total acid exposure with pH<4, mean = post-operative pathologic results from 24-hr pH-study, defined as total acid exposure with pH<4, mean * = median follow-up (months) x = median I= increase D= decrease Fr= French

AC C

EP

TE D

B

ACCEPTED MANUSCRIPT

Table 4. Included studies reporting on manometric studies

Del genio et al. 2014 47 Kleidi et al. 2013 49 *

Relative difference of effect (%)

LES resting pressure pre-LSG, mean (SD)

LES resting pressure post-LSG, mean (SD)

Relative difference of effect (%)

20

NA

NA

NA

14.2 (5.8)

10.5 (6.06)

20

14

15

18.3 (9.2)

11 (7)

14

NA (n=0)

(n=1)

7.1 (I) p=0.9 p= NS

17.1 (5.3)

12.4 (4.5)

37/65

NA

NA

NA

16.7 (6.5)

16.4 (4.5)

28/65

NA

NA

NA

10.4 (4.6)

10.1 (4.2)

17/37

NA

NA

NA

11,0 (NA)

24,0 (NA)

20/37

NA

NA

NA

8.4 (NA)

21.2 (NA)

25

10

46

21.3 (NA)

22 (NA)

23

NA

NA

360 (I) p=0.0001 NA

18.1 (NA)

21.1 (NA)

26.1 (D) p=0.01 39.9 (D) p=0.02 27.5 (D) p≤0.05 1.8 (D) p=0,8 2.9 (D) p=0,8 118.2 (I) p<0.0001 153,4 (I) p<0.0001 3.28 (I) p=0.9 12.2 (I) p=0.01

LES length pre-LSG (cm), mean (SD) NA

LES length postLSG cm, mean, (SD) NA

Relative difference of effect (%)

FU* (months)

Bougie size (Fr)

NA

6

32

NA

NA

NA

3

34

2.7 (0.9)

3.2 (1.3)

12

36

4.1 (0.3)

4.0 (0.4)

24

36

3.2 (0.5)

3.1 (0.4)

24

36

NA

NA

18.5 (I) p=NS 2.4 (D) p=0,228 3.1 (D) p=0,412 NA

0.3

35

NA

NA

NA

8

35

4.1 (NA)

3.8 (NA)

13

40

3.0 (0.8)

4,1 (1.0)

7.3 (D) p=0,741 36.7 (I) p≤0,001

1.5

34

SC

RI PT

Ineffective motility postLSGB (median %)

M AN U

Petersen et al. 2012 52

Ineffective motility preLSGA (median %)

TE D

Braghetto et al 2010 27 Burgerhart et al. 2014 29 Gorodner et al. 2014 32 Rebecchi et al. 2014 54

N

EP

Study

AC C

= follow-up N= total number of included patients A = pre-operative ineffective motility, number of patients B = post- operative ineffective motility, number of patients EWL= excess weight loss NS= non-significant, *= median follow-up (months), x= median, I= increase, D= decrease , Fr= French, NA= not answered

ACCEPTED MANUSCRIPT

Table 5. Included studies reporting on pH-Impedance studies

15

pH/impedance

Total reflux episodes preLSG 45.5

25

MII-pH

33

Total reflux episodes postLSG 59.5 53

Relative difference of effect (%) 30.8 (I) p=0.47 60 (I) p= 0.0001

Excess weight-loss (%) 19

FU* (months) 3

Bougie size (Fr) 34

56

13

40

RI PT

Methods

SC

Burgerhart et al. 2014 29 Del Genio et al. 2014 47

N

N= total number of included patients * = median follow-up (months) I= increase D= decrease

Fr= French

AC C

EP

TE D

MII-pH= combined 24-h pH and multichannel intraluminal impedance

M AN U

Study

ACCEPTED MANUSCRIPT

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

A clearly stated aim Inclusion of consecutive patients Prospective collection of data Endpoints appropriate to the aim of the study Unbiased assessment of the study endpoint Follow-up period appropriate to the aim of the study Loss to follow up less than 5% Prospective calculation of the study size Total

0

2

1

2

2

1

2

2

1

2

2

2

2

1

2

2

2

2

0

2

1

1

0

1

2

1

2

2

0

1

0

0

1

1

1

1

2

2

2

2

2

1

1

2

1

1

1

1

2

2

1

1

2

1

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

1

1

2

2

2

1

1

2

2

1

1

1

2

2

2

0

2

1

2

2

2

1

2

2

2

2

2

2

2

2

2

0

1

1

1

0

1

0

2

0

0

0

0

0

0

0

0

0

0

0

9

13

9

13

11

8

11

12

10

10

8

19

23

24

25

26

27

28

29

30

31

32

33

2

M AN U

2

22

RI PT

MINORS score

SC

Table 6. MINORS score of included studies 20

21

2

1

2

2

2

1

2

2

2

2

2

2

2

2

2

2

1

1

1

2

0

0

1

0

0

1

2

0

1

1

1

2

1

2

2

1

2

2

1

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

2

1

2

1

1

1

2

2

1

2

2

1

2

2

2

2

1

1

2

2

2

2

2

2

2

2

2

2

2

1

2

2

2

2

2

2

2

2

2

2

2

0

0

0

1

0

1

2

1

2

2

0

2

2

0

2

0

0

TE D

2

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

9

12

11

12

12

10

10

10

10

10

12

14

9

11

8

13

12

8

12

13

12

10

EP

0

AC C

1 Abrahim et al., 2 Arias et al., 3 Braghetto et al., 4 Braghetto et al., 5 Burgerhart et al., 6 Carter et al., 7 Catheline et al., 8 Gorodner et al., 9 Howard et al., 10 Kehagias et al., 11. Kular et al., 12 Lakdawala et al., 13 Moon et al. 14 Tai et al., 15 Sheppard et al., 16 Soricelli et al., 17 Vage et al., 18 Zhang et al., 19 Carabotti et al. 20 Chopra et al., 21 Cottam et al., 22 Daes et al.,21 Cottam et al., 22 Daes et al., 23 Del Genio et al, 24 DuPree et al., 25 Kleidi et al., 26 Moon Han et al., 27 Mohos et al., 28 Petersen et al., 29 Rawlins et al., 30 Rebecchi et al. 31 Santonicola et al., 32 Sharma et al., 33 Weiner et al. The items are scored 0 (not reported), 1 (reported but inadequate) or 2 (reported and adequate). The global ideal score being 16 for non-comparative studies and 24 for comparative studies.

ACCEPTED MANUSCRIPT

Table 7. Excluded studies

1. Abd Ellatif et al. 2014 58

Cohort includes patients undergoing conversion to gastric bypass or re-sleeve. Furthermore, the authors did not report the number of patients with pre-operative GERD No pre-operative prevalence of GERD reported. Cohort also includes open procedures, patients with previous bariatric surgery and patients who underwent conversion to LRYGB

3. Braghetto et al. 2012 60 4. Boza et al. 2012 61 5. Clapp et al. 2013 62

No comparison with pre-operative GERD symptoms or preoperative 24-hr pH results No reports on GERD in full text.

1395

26

560

M AN U

2. Bohdjalian et. 2010 59

N

773

7. Daes et al. 2014 64

Includes previous banding and previous sleeve gastrectomy.

382

8. Dhahri et al. 2010 65

Review and single instate data with no reports on pre- and postoperative GERD in full text. No prevalence of postoperative GERD reported

230

Population includes 36 patients undergoing LSG as a revision of failed gastric banding No pre-operative GERD reported, no reports on number of patients with GERD after LSG without GERD prior to surgery No reports on GERD, follow-up also includes patients undergoing conversion to duodenal switch Re-operation (total gastrectomy, conversion to duodenal switch) within FU period not excluded Patient group includes re-sleeve and duodenal switch

500

11. Gluck et al. 2011 68 12. Hamoui et al. 2006 69 13. Himpens et al. 2006 70 14. Himpens et al. 2010 71

EP

AC C

10. Gibson et al. 2013 67

TE D

6. Cuenca-Abente et al. 2006 63

Case series of 3 patients with hiatal hernia undergoing a primary sleeve gastrectomy with posterior crural closure including prosthetic bio absorbable mesh. Case report describing sleeve gastrectomy with concomitant repair of a large paraoesophageal hernia.

9. Eisenberg et al. 2013 66

Conclusion

RI PT

Reason of exclusion

GERD symptoms appeared immediately in the majority of the patients. 11.4% of the patients had reflux-syptoms at 1 year FU, which decreased progressively to 2% at 4 year. We observed clinically significant reflux in a large number of patients in this series, as almost a third of the patients were on chronic anti-acid medication after the procedure. Severe reflux might necessitate conversion to gastric bypass or duodenal switch. GERD could appear following LSG, patients with GERD prior to surgery must be considered for other procedures than LSG. No information regarding effect of LSG on GERD.

SC

Study

3

At 12 months follow-up, there were no mesh-related complications, one of the patients needed to resume proton pump inhibitors to control reflux.

1

At 18 months follow-up, patient was completely free of symptoms

36

Careful attention to surgical technique can result in significantly reduced GERD symptoms up to 22 months postoperatively suggesting that LSG does not predispose patients to GERD during that period. Initial results of LSG seem encouraging but long-term results are needed.

204

LSG induces remission or improvement in comorbidities of nearly all patients, translating to a decrease in medication use. GERD-symptoms decreased from 45% prevalence pre-operatively to 6% postoperatively, due to the aggressive approach of HH. LSG is a safe and effective stand-alone procedure.

118

Caution when offering open sleeve gastrectomy to patients with GERD

40

GERD is more frequent at 1 year after LSG, but at 3 years after gastric banding. LSG is a safe, effective, but appears to be associated with weight regain and

41

ACCEPTED MANUSCRIPT

quite often with reflux symptoms in long-term follow-up.

20. Melissas et al. 2008 77 21. Menenakos et al. 2010 78

22. Merchant et al. 2009 79 23. Nocca et al. 2008 80 24. Omana et al. 2010 81 25. Pallati et al. 2014 82 26. Pham et al. 2014 83

1

No postoperative recurrence of GERD

85

52

RI PT

No postoperative symptoms following secondary surgery

Case series of 5 patients with paraoesophageal hernia repair with simultaneous SG, of which 2 had undergone previous antireflux surgery Study includes patients with previous laparoscopic gastric banding Study only provides postoperative resolution or improvement of symptoms, no post-operative GERD prevalence. Analyzes difference in GERD-score before and after LSG. No data presented regarding the pre- and postoperative prevalence of GERD. Study describes 23 patients who underwent hiatal hernia repair next to sleeve gastrectomy, no clear reports concerning pre- and postoperative GERD symptoms or esophageal function tests.

LSG affects the behaviour of the esophagogastric junction in a way that is not clear and predictable, which may have to do with variations in the final shape of the sleeve. Older patients had a significantly higher rate of a concurrent hiatal hernia repair. LSG is safe and very efficient in patients aged >60, despite higher rates of perioperative comorbidities, and Pre-existing GERD symptoms were either treated or significantly improved following SG, some patients developed GER symptoms after SG.

SC

19. Melissas et al. 2007 76

Retrospective analysis comparing patients > 60 years undergoing LSG with younger patients. No reports on pre- and postoperative GERD. Study focusses on changes in gastric emptying following SG, no reports concerning reported GERD or changes in 24-hr pH results Study focusses on changes in gastric emptying following SG, no reports concerning reported GERD or changes in 24-hr pH results Study includes patients who underwent previous bariatric surgery

1

23

M AN U

18. Mizrahi et al . 2014 75

TE D

17. Lazoura et al. 2011 74

EP

16. Korwar et al. 2009 73

Case report describing recurrent HH after previous SG and HHR, treated with posterior hiatoplasty Case report concerning SG with concomitant HHR using biologic mesh No post-operative prevalence of GERD presented

AC C

15. Kotak et al. 2013 72

14

261

5

163

49 8207

23

GERD-symptoms were evident in two patients preoperatively, which dissolved completely. Five patients developed new-onset GERD at 6 months postoperatively, which was resolved at 24 months postoperatively. GERD-symptoms are common especially in the first few months, what could be the result of anatomic disruption of the lower esophageal sphincter, disruption of the angle of His, alterations in gastric emptying, and entrapment of food in the small pouch. At six months follow-up, none of the 5 patients suffered from GERD.

Long-term morbidity was caused by GERD (11.8%) treated by Omeprazole. Ten patients (6.1%) presented this problem before the surgery. Four patients had complete remission. LSG resulted in postoperative improvement or resolution of comorbidities associated with obesity. All common bariatric surgical procedures improve GERD, with LRYGB being superior compared to LSG. Laparoscopic sleeve gastrectomy combined with a paraesophageal hernia repair is feasible in morbidly obese patients.. Surgeons with the skill set to repair paraesophageal hernias should do a combined procedure because it is feasible, and can reduce the cost of multiple hospital admissions

ACCEPTED MANUSCRIPT

29. Sieber et al. 2014 86 30. Soricelli et al. 2010 87

Cohort also includes redo after failed laparoscopic gastric banding Case series of 6 patients undergoing SG with concomitant HHR

31 Varban et al. 2014 88

Study includes open sleeve gastrectomy

32.Varela et al. 2009 89

Case report of morbidly obese patient with HH undergoing SG with biomesh hiatoplasty

88

The addition of anti-reflux procedures (hiatoplasty / cardioplication) significantly reduced GERD.

114

Both LSG as gastric banding are safe without major reflux-related pulmonary symptoms. Lower incidence of cough with LSG. Considerable improvement or even remission of comorbidities.

68 6

RI PT

28. Shitrit et al, 2013 85

All patients were selected on pre-operative GERD and LSG was performed together with antireflux procedure. It is unknown what the exact pre- and postoperative prevalence of GERD in control group is. No data concerning prevalence of pre-operative GERD.

1567 1

M AN U

AC C

EP

TE D

N= total number of included patients

After four months of follow-up, GERD symptoms resolved in 75% of the symptomatic patients. Overall acid-reducing medication went from 37% to 36.7 % during one year FU. GERD symptoms are common after SG.

SC

27. Santoro et al. 2014 84

There was no postoperative recurrence of GERD at 6 months follow-up

ACCEPTED MANUSCRIPT Figure 1. Flow sheet literature search

RI PT

Records identified through database searching n= 385 Pubmed n= 149 Embase n= 226 Cochrane n= 1 CINAHL n= 9

M AN U

Records screened based on title or abstract n= 230

SC

Duplicate records removed n= 155

Records removed due to irrelevance n= 165

EP

TE D

Full text articles assessed for eligibility n= 65

AC C

Studies included in qualitative and quantitative analysis n= 33

Articles excluded n= 32

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

Figure 2. Forrest plot of the effect of laparoscopic SG on the prevalence of GERD symptoms

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

Figure 3. Forrest plot of the pooled incidence of new-onset GERD symptoms