Fuchs K.H., Babic B., Breithaupt W., Dallemagne B., Fingerhut A., et al. EAES recommendations for the management of gastroesophageal reflux disease // Surg Endosc (2014) 28:1753-1773.

: Fuchs K.H. / Babic B. / Breithaupt W. / Dallemagne B. / Fingerhut A. / Furnée E.J.B. / Granderath F.A. / Horvath P. / Kardos P. / Pointner R. / Savarino E.V. / Van Herwaarden-Lindeboom M. / Zaninotto G. / EAES

PMID: 24789125 doi.org/10.1007/s00464-014-3431-z

EAES recommendations for the management of gastroesophageal reflux disease

Karl Hermann Fuchs, Benjamin Babic, Wolfram Breithaupt, Bernard Dallemagne, Abe Fingerhut, Edgar Furnee, Frank Granderath, Peter Horvath, Peter Kardos, Rudolph Pointner, Edoardo Savarino, Maud Van Herwaarden-Lindeboom, Giovanni Zaninotto

Received: 20 December 2013/Accepted: 8 January 2014/Published online: 2 May 2014 © Springer Science+Business Media New York 2014


Background Gastroesophageal reflux disease (GERD) is one of the most frequent benign disorders of the upper gastrointestinal tract. Management of GERD has always been controversial since modern medical therapy is very effective, but laparoscopic fundoplication is one of the few procedures that were quickly adapted to the minimal access technique. The purpose of this project was to analyze the current knowledge on GERD in regard to its pathophysiology, diagnostic assessment, medical therapy, and surgical therapy, and special circumstances such as GERD in children, Barrett’s esophagus, and enteroesophageal and duodenogastroesophageal reflux.

Methods The European Association of Endoscopic Surgery (EAES) has tasked a group of experts, based on their clinical and scientific expertise in the field of GERD, to establish current guidelines in a consensus development conference. The expert panel was constituted in May 2012 and met in September 2012 and January 2013, followed by a Delphi process. Critical appraisal of the literature was accomplished. All articles were reviewed and classified according to the hierarchy of level of evidence and summarized in statements and recommendations, which were presented to the scientific community during the EAES yearly conference in a plenary session in Vienna 2013. A second Delphi process followed discussion in the plenary session.

Results Recommendations for pathophysiologic and epi-demiologic considerations, symptom evaluation, diagnostic workup, medical therapy, and surgical therapy are presented. Diagnostic evaluation and adequate selection of patients are the most important features for success of the current management of GERD. Laparoscopic fundoplication is the most important therapeutic technique for the success of surgical therapy of GERD. Conclusions Since the background of GERD is multi-factorial, the management of this disease requires a complex approach in diagnostic workup as well as for medical and surgical treatment. Laparoscopic fundoplication in well-selected patients is a successful therapeutic option.

Keywords: GERD, Gastroesophageal reflux disease, Laparoscopic fundoplication, Barretts esophagus, Proton pump inhibitor, PPI

Gastroesophageal reflux disease (GERD) is one of the most frequent benign disorders of the upper gastrointestinal tract. Management of GERD has always been controversial since modern medical therapy is very effective, but laparoscopic fundoplication is one of the few procedures that was quickly adapted to the minimal access technique and developed a large following in surgery. There have been several consensus conferences in the past that parallel the new developments in the diagnostic and therapeutic management of the disease [1-6], including one from the EAES (European Association of Endoscopic Surgery and Allied Techniques) [1]. In view of the expanding amount of literature, the boards of the EAES have decided to renew its guidelines on GERD by establishing a new consensus conference in 2013.

The purpose of this project was to analyze current knowledge on GERD in regard to its pathophysiology, diagnostic assessment, medical therapy, and surgical therapy, and special circumstances such as GERD in children, Barretts esophagus, and enteroesophageal and duodeno-gastroesophageal reflux.

Material and methods

Constitution of the expert panel

A group of experts was determined based on their clinical and scientific expertise in the field of GERD. Members were to be independent from industry-driven methods, representative of different subspecialties involved in GERD, and be distributed throughout Europe. Accordingly, the expert panel consisted one gastroenterologist (ES), one pulmonologist (PK), nine surgeons (WB, BD, AF, KHF, EF, FG, PH, RP, and GZ), and one pediatric surgeon (MvH). The project was assisted in Frankfurt by a surgical coworker (BB). The group was finalized in early 2012.

A basic list of important items with respect to GERD was established by the members in Frankfurt and circulated to   the   others,   and   a   critical   response   and   possible corrections were requested. For the literature research we followed the concept as published in other EAES consensus projects [7, 8].

Initially, in 2012, the core group in Frankfurt (KHF, WB, and BB) performed a systematic search for information in Medline via PubMed and the Cochrane Library using the following items or search terms: GERD epidemiology, pathophysiology, natural course; hiatal hernia; GERD symptoms; GERD indication for surgery, GERD medical therapy, fundoplication; Redo fundoplication; Barretts esophagus, duodenogastroesophageal reflux, and GERD in children. A total of 18,490 leads were evaluated and, of these, 4,900 abstracts were read and selected for further analysis, following the hierarchy of research evidence and clinical evidence. All articles were reviewed and classified according to the hierarchy of level of evidence [9].

In May 2012 a project plan, together with a literature list and a preliminary list of GERD items, was distributed among the panelists. All panelists were given tasks and asked to focus on certain items according to their subspe-cialty. They were asked to check the literature list for completeness. A first-draft statement on the different items was created in August 2012 after collecting all the information from the panelists and circulated for evaluation and changes before the first face-to-face meeting.

A revised draft was circulated and the first face-to-face meeting was held in Frankfurt at the end of September 2012. On this occasion, an in-depth discussion on each item began during the one-and-a-half-day meeting. The selected literature underwent critical appraisal in regard to consistency and valid clinical background. This information and the results of these discussions were transformed into statements, along with the level of available evidence and comments for further explanation, as necessary. The resulting document was circulated for further completion of each item, including diagnostics, medical therapy, surgical therapy, failures, and Barretts esophagus. During the following months a second period of reassessment of the chosen statements, literature review and incoming additional information was performed by email exchange.

A second face-to-face meeting was organized in January 2013 to reevaluate all items, statements, and their corresponding evidence level as well as the possible consensus among the panelists. Again, there was an in-depth discussion on each item and the results were summarized in statements and comments. Some items were dropped and others were included in different sections.

The strength of an items recommendation was based on the level of evidence and indicated by the word ‘must, should, or can according to the grade A, B, or C [7– 9]. The degree of consensus was expressed as the percentage of agreement for or against a certain item. If the result of discussion led to controversial standpoints, it was clearly stated in the document. In the Results section, the grade of recommendation was expressed as GoR, the expert panels consensus as ExC, and the scientific community consensus as SCC, all three as percentage.

The results of the meeting were reformulated and summarized in an updated version of the document which was circulated for a final Delphi round prior to the EAES meeting in Vienna.

During the final consensus conference at the plenary session of the 22nd annual EAES congress in Vienna in June 2013, the consensus statements were presented to the scientific community for further discussion and input. To have measurable and representative input from the scientific community, a questionnaire presenting all items was distributed to the audience for assessment and feedback. The answer for each item was selected from agree, partially agree, indifferent, partially disagree, and completely disagree. The questionnaires were collected at the end of the session and evaluated. The results of the communitys agreement or disagreement on the items are documented in the Results section. A disagreement of more than 5 % led to revision of the statement.

After consideration of the feedback of the audience and further comments by the panel, an additional and final Delphi process was initiated to achieve a final consensus, which is presented here.



In spite of some inconsistencies (defined later), for the purpose of this consensus conference, we have adopted the Montreal definition of gastroesophageal reflux disease (GERD). GoR C; ExC 100 %; SCC 95 %

Endoscopic findings in GERD allow one to distinguish between Nonerosive reflux disease (NERD), erosive reflux disease (ERD), and Barretts esophagus (BE). In addition to normal endoscopy, diagnosis of NERD requires a satisfactory response to PPI therapy and/or an abnormal acid exposure and/or a positive symptom association with documented reflux episodes. GoR C; ExC 100 %; SCC 98 %

In Europe, the two most widely used endoscopic classifications of esophagitis in GERD are the Savary and Miller classification and the Los Angeles Classification. GoR C; ExC 100 %; 95 %

In the Montreal consensus meeting, the disease was classified into esophageal and extraesophageal syndromes. In addition, the group recognized laryngitis, cough, asthma, and dental erosions as possible GERD syndromes [5]. After in-depth discussion, the panel felt that this did not completely reflect the current clinical situation and differentiated the symptomatic presentation of GERD in more detail [46]. As endoscopic findings are assessed differently in many European countries, the most widely accepted classifications should be used [1013].


GERD is a multifactorial disorder, related mainly to failure of the antireflux mechanisms. The pathophysiologic components of GERD, which can be involved either alone or combined, are a defective antireflux barrier (mechanically defective LES, inappropriate transient LES relaxations, hiatal hernia), delayed gastric emptying, and impaired esophageal clearance. GoR C; ExC 100 %; SCC 100 %

GERD is a multifactorial process in which esophageal and gastric changes are involved. The major pathophysiologic causes are the incompetence of the lower esophageal sphincter (LES), transient sphincter relaxations, insufficient esophageal peristalsis, altered esophageal mucosal resistance, delayed gastric emptying, and antroduodenal motility disorders with pathologic duodenogastroesophageal reflux as well as altered hiatal and gastroesophageal anatomy [1419]. Changing and deteriorating hiatal anatomy involves the hiatal crura, the phrenoesophageal ligament, and esophageal shortening [1921]. Several factors such as stress, obesity, pregnancy, and diet as well as drugs play an aggravating role in this process [46].


Epidemiologic data on GERD are not reliable. Based on symptoms, the prevalence ranges between 0.1 and 20 % in industrial countries. GoR D; ExC: 100 %; SCC 89 %

Data are based merely on subjective symptoms such as heartburn and regurgitation [22, 23].

Natural course

GERD is a chronic disease. The majority of patients with GERD will remain within the initial level of severity of the disease. Only a proportion of patients will progress and develop furthercomplications.GoRB;ExC100 %;SCC98 % The majority of patients with GERD will remain stable over time and within the level of severity of the disease [24, 25]. However, a small proportion (4-7 %) of patients have progressive disease with usually deteriorating anatomy and function as well as increasing severity of symptoms and decreasing quality of life [19, 23, 25]. A few patients with severe GERD can even develop detrimental aspiration, most often associated with advanced age, other comorbidities, and large hiatal hernias, which aggravate the exposure to reflux, accounting for some deaths related to GERD [26].

Anatomy and hiatal hernias

In GERD, hiatal hernia is a very frequent finding, found in up to 80-90 % of the surgical patient population. GoR B; ExC 100 %; SCC 89 %

Hiatal hernia is defined as an anatomical abnormality consisting of a protrusion or migration of intra-abdominal contents through an enlarged hiatal opening at the diaphragm [14, 27, 29]. When this develops over time, a hernia sac forms while the hiatal phrenoesophageal membrane and mediastinal and abdominal connective tissue deteriorate. Hiatal hernia is found in up to 80-90 % of GERD patients [14, 20, 2729].

Even though the size and shape of a hernia can very markedly, the surgical principles of dissecting a hiatal hernia are similar for small and large hernias. A surgically relevant classification of hiatal hernia should be used, because indications for certain surgical and endoscopic techniques as well as patient information and informed consent may depend on the presence of symptoms and different types of hernias. GoR C; ExC 100 %; SCC 95 %

There are several classifications of hiatal hernia [14, 27 30]. The most frequently used is a topographic description [14, 27, 29]. Another very useful classification is an endoscopically generated, which allows for a more functional assessment [30]. In a sliding hiatal hernia, a circumferential insufficiency of the phrenoesophageal ligament has caused a complete circular migration of the gastroesophageal junction into the lower mediastinum, which can grow into an intrathoracic stomach translocation. In a true paraesophageal hernia there is a local failure of the phrenoesophageal ligament causing a paraesophageal herniation of the fundus, while the gastroesophageal junction remains at the hiatal level. In a partial or complete upside-down stomach, the stomach has turned into the hernia sac in the mediastinum and herniation of other organs such as the colon can occur.

Since the surgical principles of dissecting and taking down a hiatal hernia are similar independent of the hernias size and rotational status, the classification of a hiatal hernia is not of major importance with respect to its repair by an experienced surgeon. However, a surgically relevant classification may be useful when certain special surgical and endoscopic techniques are indicated and for patient information and obtaining informed consent, since size and shape still can play a role in the pathophysiology and symptomatic presence.

Surgical requirements are an adapted approximation of the crura to narrow the hiatal orifice with nonresorbable sutures and resection of the hernia sac with care being taken to preserve the vagal nerves. GoR C; ExC 100 %; SCC 98 %

Narrowing the hiatus by adapted crural closure with nonresorbable sutures in addition to resection of the hernia sac after extensive mobilization of the esophagus in the mediastinum has been documented [14, 21, 31]. Relevant surgical problems include careful preservation of the vagal nerves, attention to anatomical variations at the hiatus, and recurrence despite adequate surgical technique due to tissue weakness and failure to establish stable adhesion after surgery. Recently, new efforts to evaluate the hiatus more precisely in order to classify the risk of failure and possibly prevent this failure by the use of meshes have been emphasized [3235].

Clinical presentation of GERD: typical and atypical symptoms

GERD can cause a variety of gastroesophageal (typically heartburn and regurgitation) and extraesophageal symptoms. GoR B; ExC 100 %; SCC 100 %

Although heartburn and regurgitation are characteristic of GERD, they overlap substantially with other disorders such as dyspepsia or somatoform disorders. GoR C; ExC 100 %; SCC 100 %

Patients with GERD can also present with dysphagia, upper gastrointestinal bleeding, chest pain, and epigastric pain. These symptoms (red flag symptoms) attest to severe acute disease and should be clarified by immediate appropriate diagnostic investigations. GoR C; ExC 100 %; SCC 97 %

The multifactorial pathophysiologic background of GERD accounts for the manifold clinical presentation [14, 17, 19, 27, 3640]. In addition, symptoms suggestive of GERD show a considerable overlap with other disorders such as functional heartburn, esophageal hypersensitivity, functional dyspepsia, irritable bowel syndrome, respiratory disorders, eosinophilic esophagitis, and disorders of the mouth and throat [4147]. Thus, symptoms are not reliable for confirming the diagnosis of GERD.

In the Montreal consensus meeting [5], clinical manifestations of GERD were differentiated in only two syndromes, esophageal syndromes and extraesophageal syndromes, subject to the criticism of the panelists. The panelists found evidence to claim that there are esophageal, gastrointestinal, and extraesophageal (respiratory and oro-pharyngeal) symptoms associated with GERD [3653]. Esophageal symptoms are heartburn, regurgitation, and thoracic pain. Heartburn (also known as retrosternal burning and substernal burning) from the epigastrium upward is the most typical and frequent symptom in GERD. Heartburn can be present in 6-20 % of dyspepsia patients [36 38]. Regurgitation of refluxed gastroduodenal contents from the stomach into the hypopharynx and/or mouth is the second most important symptom in GERD, with a prevalence of 33-86 % [3638, 53].

Among the gastrointestinal symptoms, epigastric pain is present in 70.5 % of patients with foregut symptoms and in 12-67 % of those with documented pathologic acid reflux. The overlap with dyspepsia and somatoform disorders is large [38, 4147].

Dysphagia is also potentially related to GERD, indicating an impaired passage throughout the esophagus. It can also be a red flag symptom, potentially caused by a tumor, requiring immediate evaluation [5].

Extraesophageal symptoms (EES) (e.g., cough, hoarseness, globus, and shortness of breath) can be associated with syndromes such as reflux cough syndrome, reflux laryngitis syndrome, reflux asthma syndrome, and reflux dental erosion syndrome. Further potential extraesopha-geal manifestations include idiopathic pulmonary fibrosis, pharyngitis, sinusitis, and otitis, which are currently under scrutiny. GoR C; ExC 100 %; SCC 98 %

Extraesophageal symptoms (EES) include respiratory and oropharyngeal symptoms such as chronic cough, hoarseness, sore throat, and pharyngeal burning. In addition, a burning sensation of the tongue and mouth, a globus sensation, and dental erosions can be related to GERD [5]. The term extraesophageal reflux (EER) is used for respiratory-related symptoms. Although there is no consensus definition of EER, common sense leads to define EER as related to lesions and/or symptoms caused by gastro-esophageal reflux that reaches structures above the upper esophageal sphincter [5].

The Montreal consensus proposed several syndromes and association of syndromes in GERD [4]. The level of evidence, particularly for the latter, is low. Established associations are reflux-cough syndrome [5456], reflux-laryngitis syndrome [57, 58], reflux-asthma syndrome [59, 60], and reflux-dental erosion syndrome [61], while the proposed associations include pharyngitis [62, 63], sinusitis [62], idiopathic pulmonary fibrosis [64, 65], and otitis [62].

Today EER can be regarded as an important contributing factor to EES [66]. Of note, by far not all patients with reflux suffer from such syndromes. For example, in reflux-chronic cough syndrome, hypersensitivity of the anatomically closely related cough reflex circuit to the LES innervation may play a crucial role [67]. This changing paradigm of understanding reflux-respiratory disease correlations makes it very difficult to collect epidemiologic data [67, 68]. Sampling gaseous, aerosolized reflux in the pharynx might be more appropriate for the assessment of laryngopharyngeal reflux (LPR), further complicating sampling of epidemiologic data on EER [6870].

Diagnostic investigations

The most important diagnostic investigations to prove the presence of GERD are endoscopy and long-term impedance pH monitoring (or pH monitoring). For accurate placement of the impedance pH probe, manometry measurements are recommended. The test should be performed after adequate washout of PPI or antisecretory drugs (discontinuation 2 weeks before testing). GoR B; ExC 100 %; SCC 97 %

It is essential to differentiate between the investigations necessary to establish the diagnosis of GERD and those necessary to establish the indication for surgery or any other invasive therapy [5, 11, 17, 37, 71, 72]. Upper gastrointestinal endoscopy is an important investigative tool to document GERD when there is endoscopic visualization of mucosal damage such as signs of reflux esophagitis [11, 73, 74]. The other important diagnostic investigative tool is pH monitoring or impedance pH monitoring, which is necessary to objectively document pathologic acid exposure and/ or other pathologic reflux activities [7579]. Impedance pH monitoring increases the diagnostic value of these functional studies by quantifying acid and nonacid reflux [80] and by providing a correlation between symptoms and documented reflux episodes [8184]. In addition, esopha-geal pH monitoring has important prognostic value in patient selection for antireflux surgery [85].

Esophageal manometry is not important in establishing the diagnosis of GERD. It does, however, have some value as a marker of severity of the disease in that LES incompetence is associated with more severe disease and long-term progression [1517, 19, 86]. Manometry studies are important prior to any surgical procedure to evaluate motility disorders, especially spastic motility disorders or achalasia [31, 71, 72, 83, 8690].

When atypical symptoms are predominant, a symptom correlation with proven reflux episodes should be considered for accurate diagnosis. GoR B; ExC 100 %; SCC 92 %

The more atypical symptoms present in a given patient, the more detailed diagnostic assessment should be performed prior to surgery to detect all functional defects [72, 90]. When extraesophageal symptoms are present or, especially, are the chief complaints, it is extremely important to correlate the atypical symptoms with the reflux episodes to justify invasive antireflux therapies [91].

Further diagnostic investigations may be needed to verify functional abnormalities and establish the indication for surgery or other invasive therapies. Investigations that can evaluate the status of esophageal and gastric function include high-resolution manometry (HRM), video-radiography, scintigraphy, and others. GoR B; ExC 100 %; SCC 93 %

HRM facilitates the procedure for the patients. Dynamic barium sandwich videography is important in evaluating patients with dysphagia. In cases of large hernias, a barium study can provide information about the possibility of a short esophagus [21]. In GERD patients with nausea and vomiting as the major complaint, gastric emptying studies and duodenogastroesophageal reflux assessment should be done to evaluate the presence of a gastroduodenal motility disorder such as delayed gastric emptying [9295].

Medical therapy

The goal of medical therapy in GERD is to control heartburn, heal gastroesophageal mucosal injuries, and improve quality of life. GoR A; ExC 100 %; SCC 100 %

GERD, both ERD and NERD, is associated with significant impairment of quality of life [3, 4, 96101]. Thus, the goal of medical therapy in GERD is to control heartburn, heal gastroesophageal mucosal injuries, and improve quality of life [9698].

Lifestyle and dietary modifications may benefit some selected patients with GERD, but alone they are almost ineffective in relieving reflux symptoms. GoR B; ExC 100 %, SCC 97 %

Patients should avoid large meals and lying down within 3 h after eating. Moreover, ingestion of fatty or spicy foods, chocolate, coffee, peppermint, citrus fruits and juices, tomato, carbonated drinks, and alcohol may favor the occurrence of reflux events and GERD symptoms [35, 102, 103]. Changes in lifestyle may include sleeping with the head elevated and stopping smoking [103, 104]; however, there is little or no evidence for the efficacy of these interventions. Conversely, recent data suggest that a high BMI is an independent risk factor for the development of GERD and that the clinical efficacy of medical therapy seems to be influenced by the patient being overweight/ obese. Weight loss or avoidance of weight gain should be considered to reduce the risk of GERD and to obtain a better outcome from acid suppressant therapy [104106].

Antacids are well tolerated, safe, and effective in reducing heartburn and controlling acid regurgitation (typical symptoms of GERD) in patients with mild reflux disease. GoR B; ExC 100 %; SCC 96 %

Antacids such as alginate-based preparations are well tolerated and effective in reducing heartburn and improving quality of life [107110]. However, they are less effective in controlling nonacid reflux and regurgitation [111].

Acid suppressive drugs are safe and effective in patients with esophageal syndromes. Proton pump inhibitors (PPIs) are more powerful than H2 receptor antagonists in providing mucosal healing and symptomatic relief. GoR A; ExC 100 %; SCC 100 %

H2receptor antagonists (H2RAs) Acid suppression represents the mainstay of GERD medical treatment. H2RAs have shown lower efficacy than PPIs in acid suppression, but given in divided doses they may be effective in some patients with less severe forms of GERD [112, 113]. Moreover, as gastric acid is still secreted particularly during the night, despite twice-daily PPIs, it has been suggested that the addition of a nighttime H2RA might be helpful in suppressing this acid reflux, but insufficient data are available to recommend it [114]. However, it is important to note that continuous use of H2RAs is associated with the development of tolerance to them, limiting their long-term use and efficacy as add-on therapy [115].

Proton pump inhibitors (PPIs) By inhibiting the H?-K ? adenosine triphosphatase pump of the parietal cell, PPIs potently reduce gastric acid secretion and provide the most powerful symptomatic relief and heal esophagitis in the majority of the patients [35, 116, 117]. Moreover, they are safe and have been used world-wide for more than a decade [116, 118, 119]. Standard doses of omeprazole, lansoprazole, pantoprazole, esomeprazole, and rabeprazole for the most part have shown comparable rates of healing and remission of erosive esophagitis [119, 120], although there are several physiologic studies showing a mild to moderate benefit of one drug over another [121, 122]. Since PPIs are best absorbed in the absence of food, patients should be advised to take their PPI between 30 and 60 min prior to eating, usually before breakfast or prior to the evening meal [123].

In patients with a partial or unsatisfactory response to once-daily PPI dose, twice-daily PPI may be of help to improve symptom relief. Nonresponders should be further investigated. GoR B; ExC 100 %; SCC 98 %

Data supporting twice-daily PPIs (or H2RAs) rather than a standard dose for improving mucosal healing and symptom relief are weak [124, 125], even though the pharmacodynamics of the drugs logically supports twice-daily dosing [119, 126]. Expert opinion suggests twice-daily dosing of PPIs in patients with an esophageal syndrome and unsatisfactory response to once-daily dosing or in patients with atypical or extraesophageal symptoms [119, 127, 128]. Nonresponders to twice-daily PPI therapy should be considered treatment failures and further investigated [129, 130].

Promotility drugs as monotherapy or add-on therapy are not recommended for the routine management of GERD. Prokinetics may be used in selected patients in conjunction with antisecretory agents. GoR C; ExC 100 %; SCC 93 %

Esophageal and gastric motility abnormalities are relevant in the pathogenesis of GERD. Therefore, promotility drugs such as metoclopramide, bethanecol, and domperidone, given as mono- or add-on therapy, usually before a meal, may be useful to control reflux symptoms. However, the frequent side effects have largely limited the regular use of these drugs [131, 132].

Indication for surgical therapy in GERD

Prior to the indication for surgery or any other invasive therapy, it must be proven that patients are in need of long-term treatment of GERD. GoR B; ExC 100 %; SCC 98 %

Patients with continuous reduced quality of life, persistent troublesome symptoms, and/or progression of disease despite adequate PPI therapy in dosage and intake should be offered laparoscopic antireflux surgery after proper diagnostic testing. GoR A; ExC 100 %; SCC 98 %

The aim of therapy is to resolve the symptoms, treat and prevent complications, and improve the patients quality of life. If symptoms and a reduced quality of life persist despite an adequate PPI dosage and proper intake, patients should undergo further testing to evaluate the severity and complexity of the disease and possible indication for antireflux surgery. The basis for this is the available evidence that laparoscopic antireflux surgery can improve quality of life in patients with altered anatomy, massive acid exposure, nonacid reflux, severe reduction in quality of life, and progressive disease with need to increase PPI dosage over the years [31, 71, 72].

PPI therapy is always the primary therapy for acute GERD. If a patient needs long-term treatment, both medical and more invasive options must be considered. Several randomized trials comparing PPI therapy with antireflux surgery have been conducted. Three of these trials [133 135] showed an advantage for surgical therapy in outcome and cost-effectiveness after a few years, whereas one showed an advantage for PPI therapy after 5 years [117]. The conclusion from these studies and other large case-control series from experienced centers is that patients should be well selected for surgery so that they benefit from an increase in quality of life [117, 133138].

The following list of criteria drawn from the literature contains the most important and most frequently mentioned features leading to the indication for antireflux surgery:

  • Typical symptoms for GERD [85]
  • Documented symptom-reflux correlation [83]
  • Year-long reflux history [14, 16, 86]
  • Reduced quality of life [31, 71, 72]
  • Positive PPI response [85]
  • Need for PPI dosage increase [25, 117, 133, 134]
  • Hiatal hernia [14, 19, 20]
  • Documented esophagitis (in the past before PPI) [14, 19, 134136]
  • Proven LES incompetence [1417, 19, 86]
  • Documented acid reflux [14, 17, 19, 71, 72, 77, 92]

GoR B; ExC 100 %; SCC 95 %

These criteria should be evaluated in each patient who is a candidate for antireflux surgery to verify as much as possible the need for long-term therapy and surgical correction [1417, 19, 20, 25, 31, 37, 71, 72, 77, 83, 8587, 9294, 117, 133135].

Patients with proven GERD, good response to PPI, dependent on PPI, and acceptable quality of life under adequate PPI therapy may be considered for surgery if she/ he so desires. Information about the side effects and risks of antireflux surgery is particularly relevant in this category of patient. GoR C; ExC 100 %; SCC 91 %

Patient with documented GERD and sufficient quality of life under adequate PPI therapy can continue medical treatment. However, some patients may want surgical therapy. The indication for surgery—the patients wishis a critical issue since 5-10 % of these patients run the risk of reduced quality of life postoperatively [31, 71, 72, 117]. This risk should be part of the information presented to the patient before he/she gives informed consent.

In patients with proven GERD and impaired esophageal motility, a fundoplication (partial or total) can be performed without an increased risk of dysphagia. In cases of severe hypomotility, the data are controversial, but a partial fundoplication might be considered. GoR C; ExC 100 %; SCC 91 %

The influence of esophageal motility disorders on postoperative results was investigated in several randomized trials [139141]. Keeping the different definitions of esophageal motility disorders in mind, laparoscopic fundoplication can be either partial or total. However, for patients with aperistalsis, the results in the literature are controversial [139145].

In NERD patients and those with hypersensitive esophagus, antireflux procedures can improve quality of life if adequate indication criteria are fulfilled. GoR C; ExC 100 %; SCC 95 %

Limited evidence from preliminary data has shown good results from laparoscopic Nissen fundoplication in patients with NERD and in patients with normal acid exposure and positive symptom association with acid and/or nonacid reflux episodes (hypersensitive esophagus), if the patients are selected very carefully [146, 147].

Patients with documented pathologic laryngopharyngeal reflux (LPR) and positive symptom correlation may benefit from a laparoscopic fundoplication. There is only limited evidence on the efficacy of antireflux surgery in patients with documented LPR associated with nonacid reflux. GoR C; ExC 100 %; SCC 93 %

Several case-control studies have shown good results for laparoscopic Nissen fundoplication in carefully selected patients with LPR or GERD-related respiratory symptoms [67, 148-153].

Patients with GERD and who are obese can benefit from a bariatric procedure rather than from an antireflux procedure. Indications according to BMI and the best procedure to use (gastric bypass, sleeve, others) are currently being debated. GoR C; ExC 87 %; SCC 89 %

In obese patients with BMI >35 kg/m2 and GERD, a traditional antireflux operation may not be sufficient. In moderate cases, a combination of sleeve gastrectomy with sphincter and hiatal repair can be considered. In more severe cases, both problems can be solved by bariatric surgery [154, 155].

Standard technique of primary laparoscopic fundoplication

The rationale for surgery is to create a functional antireflux barrier. The reconstruction of the antireflux barrier consists of three fundamental components: (1) proper length of the intra-abdominal esophagus, (2) crural repair, and (3) fundoplication. GoR B; ExC 100 %; SCC 98 %

The operative strategy of mechanical augmentation of the cardia, as introduced by Nissen [156], is still valid and successful [31, 71, 72, 117, 133-135, 157]. Several modifications to fundoplication (complete, posterior, or anterior partial wraps) have been shown in randomized trials to efficiently reduce gastroesophageal reflux and improve quality of life over years [31, 71, 72, 117, 133-135, 157-160]. Both partial and total fundoplications must meet the basic standard of being efficient and providing longevity by restoring the intra-abdominal segment of the esophagus, using only the fundus to create the wrap, placing the valve at the level of the gastroesophageal junction, and adequately approximating the crura [157].

Laparoscopic partial and total fundoplications are currently the best available surgical techniques to treat severe GERD. GoR A; ExC 100 %; SCC 99 %

Randomized controlled trials (RCTs) have shown that partial fundoplication has fewer short-term side effects. However, the available RCTs are of limited quality and power. Due to the heterogeneity with respect to the definition of dysphagia and outcomes and/or different poorly defined technical details of the procedures, results are difficult to compare. As a consequence, experienced surgeons in high-volume centers may decide between total and partial posterior fundoplication according to their own experience and outcome. GoR B; ExC 100 %; SCC 97 %

Controversy exists about the optimal shape of the wrap, whether to use complete (360°) or partial, anterior or posterior, and whether the latter should cover 240, 180, or 90 of the esophageal circumference. Several randomized trials [159-174] and meta-analyses have been published [175-182].

The two major competing procedures are the laparoscopic Nissen fundoplication and the posterior partial Toupet hemifundoplication. Meta-analyses show a similar success rate at 5 years but a higher rate of side effects (dysphagia, bloating, and flatulence) and a higher reoperation rate in the Nissen group compared to the Toupet group [160, 162, 170, 176, 179]. In contrast, large case-control studies from experienced centers show a low level of side effects with minimal enduring dysphagia, a high long-term durability, and a low reoperative rate for the Nissen procedure [31, 71, 72, 157, 183189]. Since the data are controversial, consensus is difficult and the choice of which fundoplication technique to use should be left to the individual surgeon according to his/her expertise.

Hiatal repair (approximation) is obligatory in the surgical treatment of hiatal hernia. GoR B; ExC 100 %; SCC 100 %

There is only indirect evidence indicating that hiatal repair should be performed during antireflux surgery [1, 2, 117, 128]. In addition, whether a radiologic hiatal hernia recurrence is clinically relevant and requires therapeutic measures is controversial [190].

Hiatal repair with mesh reinforcement may reduce hernia recurrence. However, mesh-related complications have to be considered. GoR A; ExC 100 %; SCC 98 %

Frequent recurrences, especially in patients with a large hiatal hernia, have stimulated interest in mesh reinforcement as a possible solution [191198]. Two randomized trials and other reports have shown an advantage in the use of mesh reinforcement regarding the postoperative recurrence rate of hiatal hernias.

There is increasing evidence of mesh-related complications. As a consequence, indications for mesh should be limited to patients with weak crurae and a large hiatal defect. GoR C; ExC 100 %; SCC 95 %

More recently, clinical experience has shown that the use of mesh at the hiatus can cause severe problems (e.g., recurrent dysphagia and pain, mesh dislocation and penetration) sometimes requiring major resections [197201].

Collis gastroplasty in the short esophagus

A short esophagus (SE) is a rather rare phenomenon with reports showing it ranging from 1 to 20 %. Although the final diagnosis of SE is made intraoperatively, the presence of peptic strictures, Barretts esophagus, and large hiatal hernia are considered preoperative indicators of SE. When there is a suspicion of SE, the patient should be investigated with barium studies. GoR C; ExC 100 %; SCC 95 % In an anatomically normal adult, the intra-abdominal segment of the esophagus is 23 cm long, depending on the bodys length. In a patient with long-standing GERD and persistent or recurrent esophagitis, the esophagus can be shortened [21]. If the esophagus cannot be mobilized from the mediastinum in a tension-free fashion to obtain a 2-3-cm intra-abdominal segment during an antireflux procedure, it is classified as a short esophagus. While most authors consider this a rare phenomenon, the incidence reported in literature is controversial, ranging between 1 and 20 % [21, 202-206].

If sufficient length of the intra-abdominal esophagus cannot be obtained after extensive esophageal mobilization, a lengthening procedure using Collis gastroplasty should be considered, since patients can benefit from it. There is limited evidence on the technical aspects of a Collis gastroplasty. A Collis gastroplasty should be performed by an experienced surgeon in this field. GoR B; ExC 86 %, SCC 78 %

Two meta-analyses and several case-controlled studies have shown that patients with SE can benefit from antireflux surgery combined with a Collis gastroplasty [22, 202-207]. An alternative to gastroplasty can be esophageal lengthening by dividing the posterior and, if necessary, anterior vagal nerves [208].

New emerging techniques for antireflux therapy

There is not enough evidence available to recommend an alternative option to fundoplication for severe GERD. GoR B; ExC 100 %; SCC 97 %

Several endoscopic antireflux techniques have been developed beginning in the late 1990 s. Due to limited effectiveness and/or severe complications, most of these procedures, such as EndocinchT suturing (C.R. Bard, Inc., Murray Hill, NJ), the Stretta procedure (Mederi Therapeutics Inc., Norwalk, CT), the Enteryx injection (Boston Scientific, Natick, MA), the plicator, and the EsophyxT plication (EndoGastric Solutions, San Mateo, CA), have not survived. Some procedures have had limited success [209-213]. A new laparoscopic antireflux procedure using a device to reinforce the cardia has been introduced in recent years, the magnetic scarf LINXTM (Torax Medical Inc., Shoreview, MN). The initial clinical experience has produced promising results in patients with moderate GERD with or without small hiatal hernias [214, 215].

Failures of surgical therapy and management of redo surgery

Failure is usually defined as persistent, recurrent, or new-onset symptoms. Antireflux surgery has a failure rate of 10-15 %. The main symptoms of failure are recurrent reflux symptoms and/or dysphagia. GoR A; ExC 100 %; SCC 100 %

Persistent and recurrent reflux can be due to intratho-racic wrap migration,  disruption of the wrap,  slipping, and/or telescoping. Pain and/or dysphagia can be caused by intrathoracic wrap migration, slipping, telescoping, para-esophageal herniation, mesh migration, excessive fibrosis (mesh-related or not), and/or an overly tight wrap or overly tight crural repair. Dysphagia can also be due to initially unrecognized esophageal motility disorders such as acha-lasia. A variety of symptoms (gas-bloat syndrome, inability to belch, gastric fullness, early satiety, diarrhea, nausea, and vomiting) can occur postoperatively, some due to an overly tight wrap or an overly tight crural repair, others secondary to vagal damage. GoR B; ExC 100 %; SCC 98 %

Primary antireflux surgery has a successful outcome in 85-90 % of patients up to 5 years after surgery [31, 71, 72, 117, 133135, 157, 183188]. Consequently, that means there is a failure rate of 10-15 %. Redo antireflux surgery is required in 3-6 % of all patients who undergo primary antireflux surgery [216220]. Recurrent reflux symptoms such as heartburn and regurgitation are the main complaints after unsuccessful antireflux surgery and are found in 61 % of patients with failure [219, 220]. Troublesome dysphagia is the second most frequent symptom in failed antireflux surgery (24 %). Combined recurrent reflux and dysphagia is reported in 6 % of patients. Symptoms should be the primary indication for redo antireflux surgery.

All patients seeking treatment for symptomatic failure after antireflux surgery should be evaluated to identify the causes of failure. Investigative techniques include endos-copy, manometry (HRM), esophageal 24-h (impedance) pH monitoring, barium studies, and scintigraphy. Severe dysphagia requires early endoscopic exploration and, whenever appropriate, endoscopic dilatation. If symptoms persist, revisional surgery is recommended. Excessive dysphagia and intractable pain and/or dyspnea in the early postoperative course require immediate revision after appropriate investigations. In all other failure scenarios, first-line therapy should be medical and/or supportive. GoR B; ExC 100 %; SCC 98 %

The main reason for functional failure after primary antireflux surgery is misdiagnosis. These patients usually have a primary functional disorder other than GERD such as achalasia, diffuse esophageal spasm, nutcracker esophagus, eosinophilic esophagitis, or scleroderma [219221]. Another possible cause for failure after primary antireflux surgery is the wrong procedure was used in patients with severe esophageal dys- or motility [219].

All patients with symptomatic failure after primary antireflux surgery should be extensively evaluated with several procedures to identify the cause of the failure [219 227]. This diagnostic program should include manometry, possibly a high-resolution manometry, (impedance) pH monitoring, radiographic studies such as a barium sandwich, and scintigraphy in selected cases, as well as assessment of outcome and quality of life [216, 229233].

Redo antireflux surgery should always begin with a clear definition of the anatomy. Surgeons undertaking revisional laparoscopic surgery should be able to perform total and partial fundoplication, Collis gastroplasty, and resections as necessary. Revisional antireflux surgery should be performed by a well-experienced surgeon in the field. GoR C; ExC 100 %; SCC 86 %

Anatomical alterations such as recurrent hernia or a bilobed and twisted stomach have been described as reasons for failure and subsequent redo antireflux surgery [216229]. However, an anatomical disturbance without symptoms should never be the only reason for redo surgery. Symptoms should be the primary indication for redo antireflux surgery. Conversely, postoperative anatomy as evaluated by endoscopy and/or barium studies can be normal in patients who still have symptoms.

Anatomical changes after laparoscopic antireflux procedures can be classified into several categories, including intrathoracic wrap migration, wrap disruption, telescoping, paraesophageal herniation, a tight wrap or a tight crural repair, and a bilobed or twisted stomach. With all of these conditions there has to be dissection and proper rearrangement before creating a new fundoplication [216, 219, 220].

Revisional surgery should be performed by specialized gastrointestinal surgeons with extensive experience in the field. The surgeons technical armamentarium for revi-sional surgery should include all laparoscopic, endoscopic, and thoracoscopic procedures as well as all open procedures, including major resections, as necessary to solve the problem.

Barretts esophagus

Barretts esophagus (BE) is defined as the presence of columnar mucosa and intestinal metaplasia in the distal esophagus and is the final consequence of long-standing (duodeno-) gastroesophageal reflux disease (GERD). BE is associated with a 30-150-fold increase in the risk of esophageal adenocarcinoma. GoR B; ExC 100 %; SCC 97 %

There are two definitions of BE currently in use. One, adopted in the US and continental Europe, requires the presence of intestinal metaplasia (goblet cells) in biopsies from the columnar epithelium lining the distal esophagus [234]. In the UK, on the other hand, all histological types of metaplastic epithelium (cardiac or fundic) are defined as columnar epithelium lining the esophagus (i.e., Barretts esophagus) and the presence of intestinal metaplasia is not essential to the diagnosis [235]. Since intestinal metaplasia is the only type of esophageal columnar epithelium clearly predisposed to malignancy [236], we prefer to use the first definition. The incidence of BE progression to high-grade noninvasive neoplasia or invasive neoplasia is estimated to be between 1 and 5 per 1,000 patients/year, which is 40-50 times higher than in the normal population [237, 238].

The aims of medical or surgical therapy in Barretts esophagus are to control symptoms, heal any mucosal lesions (esophagitis), prevent complications, and limit progression of BE to neoplasia. Although medical therapy is highly effective in controlling symptoms, it may be less so in abolishing gastroesophageal reflux and the progression to neoplasia. GoR B; ExC 100 %; SCC 98 %

The current treatment for BE [proton pump inhibitors (PPIs) or antireflux surgery] aims to control GERD-related symptoms and to prevent complications such as ulcer, bleeding, and stricture. There have been anecdotal reports of acid suppression therapy being able to revert intestinal metaplasia to cardiac/fundic metaplasia or squamous epithelium (and thereby reduce the cancer risk) [239].

The usual therapy for BE consists of PPI in single or double doses. It is generally believed that BE patients are more difficult to manage with medical therapies than other GERD patients, and higher PPI doses may be required. Abnormal acid exposure in the distal esophagus of BE patients is particularly evident at night when nocturnal regurgitation and related respiratory symptoms (nocturnal acid breakthrough) may occur [240].

Antireflux surgery may be more effective than medical therapy for BE and should be considered, particularly for young patients. GoR C; ExC 100 %; SCC 89 %

Antireflux surgery is a valid alternative to PPI and has the advantage of correcting the LES failure and the frequently associated hiatal hernia, as well as controlling abnormal gastric and duodenal reflux in 80-90 % of patients. One controlled study [241] and several noncontrolled studies [242246] have demonstrated better symptom control and a lower incidence of stricture after surgery compared to medical therapy. Subgroup analysis of patients with BE enrolled in the recently reported LOTUS trial showed a comparable rate of symptom control between surgery and escalating doses of PPI [247]. Since BE is frequently found in older patients, surgery should be considered for younger and fit patients, particularly in cases at high risk of progression with large hiatal hernias, severe reflux symptoms, and a long history of disease [248, 249].

There is limited evidence to show that antireflux surgery can reduce the extent of BE and the risk of progression to cancer. After antireflux surgery, endoscopic surveillance has to be maintained. GoR C; ExC 100 %; SCC 98 %

There are conflicting data regarding the influence of surgical therapy on the regression or progression of BE [243, 245, 250257]. Epidemiological studies have recently shown that progression to cancer after antireflux surgery is due mainly to subsequent recurrence of reflux, which remains the Achilles heel of antireflux surgery [259].

Given such conflicting data, endoscopic surveillance should be maintained even after a patient has undergone antireflux surgery [258, 259].

Gastroesophageal reflux and antireflux surgery in children

Although most children with gastroesophageal reflux (GER) no longer have this condition by the age of 1 year, clinically troublesome GERD can occur in a significant proportion of children and adolescents. Contrary to adults, GERD symptoms are often nonspecific. The majority of pediatric GERD patients have neurological impairment. GoR C; ExC 100 %; SCC 100 %

Gastroesophageal reflux (GER) is a normal physiologic process and can occur in up to 70 % of completely healthy newborns and infants. This GER resolves spontaneously in 95 % of the individuals by 1214 months of age [260, 261]. When GER causes troublesome symptoms and/or complications, the diagnoses of GERD can be raised, according to the Montreal Definition of GERD in adults. This definition also applies to children but with several limitations [5].


Clinical diagnosis cannot be used in infants, young children, or neurologically impaired adolescents because these individuals cannot reliably report their symptoms. Although the verbal child can communicate pain, descriptions of the intensity, location, and severity may be unreliable until the age of at least 8 years, and sometimes even later [262264].

In infants and younger children or older children with neurologic impairment, symptoms and signs associated with reflux are often nonspecific and include vomiting, excessive regurgitation, refusing to eat, anorexia, unexplained crying, choking, gagging, coughing, disturbed sleep, and abdominal pain [265].

Typical symptoms of GERD in children include recurrent regurgitation with or without vomiting, swallowing difficulties that lead to weight loss or failure to thrive, respiratory problems (wheezing, asthma, or recurrent pneumonia), abdominal pain, irritability, and sleeping problems. Anorexia or refusing to eat is significantly (p<0.05) more common and severe in children aged 15 years than in older children or adolescents [266]. Sandifers syndrome (torticollis) is a specific manifestation of GERD in neurologically intact children and entails abnormal posturing (e.g., head tilt, torticollis), because of GERD [267, 268]. When assessing GERD, rumination should be distinguished from regurgitation. Rumination is common   in   infants   and   children   with   neurological impairment, but it can also occur in subjects without obvious neurologic deficits and is considered by some to lie within the spectrum of eating disorders [269]. Older children are more likely to experience symptoms similar to those in adults such as chronic heartburn, regurgitation with reswallowing, and dysphagia.


GERD pathophysiology in children differs from that in adults in that nearly 50 % of pediatric GERD patients are neurologically impaired. In these patients prolonged supine position, spasticity, and generalized gastrointestinal dysmotility contribute to GER [270]. The higher frequency of GERD in infants is associated with transient esophag-ogastric immaturity [271]. Although the pathophysiology of GERD has still not been completely unraveled, it is known to be a multifactorial disorder, even in childhood [271, 272].

Eosinophilic esophagitis (EE) is a chronic disease characterized by eosinophilic infiltration of the esophageal mucosa and associated with clinical and endoscopic manifestations [273, 274]. The incidence of EE appears to be increasing for as yet unknown reasons. EE can occur at any age, with a clinical presentation ranging from gastrointestinal symptoms (vomiting, feeding difficulties, dysphagia, or food bolus impaction) to coexisting atopic conditions (asthma, allergic rhinitis, or eczema).

Certain underlying disorders such as neurologic impairment, esophageal atresia, chronic lung disease, and genetic disorders predispose pediatric patients to the most severe and chronic GERD, and its complications [275277].

Normal values for most gastroesophageal functional tests are lacking, which limits diagnostic accuracy. Diagnosis is established by evaluation and interpretation of symptoms and results of diagnostic assessment. GoR C; ExC 100 %; SCC 98%

Established tests for assessing symptoms of GERD in adults may be used in children. However, there are several differences and limitations. For symptom evaluation, the reliability and validity of two age-specific reflux questionnaires have been described to diagnose GERD, the infant gastroesophageal reflux questionnaire (I-GERQ) and the GERD symptom questionnaire (GSQ) [278280]. Normal values for children over 18 months of age using pH monitoring have not been established. Reflux assessment should be performed by 24-h impedance pH-monitoring [280282].

Barium swallow X-ray is useful to detect anatomic abnormalities but not for the diagnosis of GERD, since sensitivity and specificity are limited [282, 283]. Gastric emptying is measured by the 13C-octanoic acid breath test, for which normal values in children have been established [283]. 

Esophagogastroscopy with esophageal biopsy should be performed to diagnose or rule out other conditions, including eosinophilic esophagitis, infection, and Crohns disease.

The therapeutic approach should start with medical therapy. The efficacy of pediatric antireflux surgery (ARS) has a wide range, which explains why the best approach is still under debate. Although there is a lack of well-designed studies, partial fundoplication shows less severe postoperative dysphagia while maintaining similar reflux control compared to complete fundoplication. GoR B; ExC 100 %; SCC 100 %

Most symptomatic children respond well to medical treatment. Either H2 antagonists or PPI may be used in children over 1 year of age [284286]. However, when medical treatment fails, ARS may be considered [285287]. ARS is one of the most frequently performed major operations in children. A systematic review of prospective studies on pediatric ARS showed a good overall success rate (median 86 %) in terms of complete relief of symptoms [288].

A systematic review and meta-analysis comparing the laparoscopic versus open approach in children showed a shorter hospital stay, less morbidity, and earlier feeding time after laparoscopic ARS. Recurrence of reflux after either procedure was similar [289].

Several different types of fundoplication (Nissen, Toupet, and Thal) can be performed in pediatric patients with GERD. The results of several studies are controversial as some reports show a higher risk of postoperative dysphagia with the Nissen procedure compared to partial fundoplication [290292]. Recently, a first randomized trial with pediatric GERD patients was performed comparing Nissen to Thal fundoplication [292]. A meta-analysis showed that reflux control was similar after both types of fundoplication. However, partial fundoplication required significantly fewer dilatations to treat postoperative dysphagia [292]. In summary, ARS in pediatric patients with GERD shows good reflux control.

Enteroesophageal and duodenogastroesophageal reflux

Duodenogastroesophageal reflux is associated with more severe esophageal mucosal damage and BE. Fundoplication can prevent both gastric and duodenal reflux and is indicated in BE with documented enteroesophageal reflux. GoR B; ExC 100 %; SCC 96 %

The damaging effect of combined acid and duodenal juice and its components has been proven and documented in several conditions such as GERD, BE, and postoperative syndromes [14, 1719, 93, 94, 293, 294]. Fundoplication can reduce gastroesophageal reflux very effectively and is therefore indicated in patients with severe mixed pathologic reflux.

Refluxate from the small bowel into the esophagus in patients with previous gastric surgery can cause severe damage in the esophagus. As a consequence, symptomatic patients after gastric surgery with reduced quality of life and enteroesophageal reflux should undergo functional diagnostic workup. If indicated by a positive correlation between functional defects and symptoms, surgical therapy can be resection and/or duodenal diversion eventually combined with fundoplication. GoR C; ExC 100 %; SCC 89 %

Refluxate from the stomach and the duodenum/jejunum contains a mixture of acid, bile, and pancreatic enzymes, which can have a toxic effect on the esophageal mucosa and other structures of the esophageal wall [14, 17, 18, 85, 93, 94]. The damaging potential of enteroesophageal reflux was studied in the past by studying the effects of different reconstruction methods after gastric and esophageal resections [294297]. In patients after gastric resection with a short (\50 cm) jejunal limb reconstruction, in patients with a small gastric remnant, or in patients with a distal esophagectomy and gastric pull-up with an anastomosis in the lower mediastinum, there is a high probability of excessive enteroesophageal reflux with symptoms and/or esophagitis, which should be investigated by the proper methods followed by surgical correction [297299].

Acknowledgments The panelists express their gratitude to the EAES and the scientific community during the 21st EAES Congress 2013 in Vienna for their support of this work.

Disclosures Karl Hermann Fuchs, Benjamin Babic, Wolfram Bre-ithaupt, Bernard Dallemagne, Abe Fingerhut, Edgar Furnee, Frank Granderath, Peter Horvath, Peter Kardos, Rudolph Pointner, Edoardo Savarino, Maud Van Herwaarden-Lindeboom, and Giovanni Zanin-otto have no conflicts of interest or financial ties to disclose.


  1. Eypasch E, Neugebauer E, Fischer F, Troidl H (1997) Laparo-scopic antireflux surgery for gastroesophageal reflux disease (GERD). Results of a consensus development conference. Surg Endosc 11:413426
  2. Fuchs KH, Feussner H, Bonavina L, Collard JM, Coosemans W, European Study Group for Antireflux Surgery (1997) Current status and trends in laparoscopic antireflux surgery: results of a consensus meeting. Endoscopy 29:298308
  3. Dent J, Brun J, Fendrick AM, Fennerry MB, Janssens J et al (1999) Genval Workshop Group: An evidence-based appraisal of reflux disease management. Gut 44:S1S16
  4. Kahrilas PJ, Shaheen NJ, Vaezi MF, Hiltz SW, Black E, Modlin IM, Johnson SP, Allen J, Brill JV (2008) American Gastroenterological Association Medical Position Statement on the management of gastroesophageal reflux disease. Gastroenterology 135:13831391
  5. Vakil N, van Zanten SV, Kahrilas PJ, Dent J, Jones R, Global Consensus Group (2006) The Montreal Definition and Classification of GERD: a global evidence-basedconsensus. Am J Gastroenterol 101:19001920
  6. Stefanidis D, Hope WW, Kohn GP, Reardon PR, Richardson WS, Fanelli RD, SAGES Guideline committee (2010) SAGES guidelines for surgical treatment of GERD. Surg Endosc 24(11):26472669
  7. Neudecker J, Sauerland S, Neugebauer E, Bergamaschi R, Bonjer HJ, Cuschieri A, Fuchs KH, Jacobi C, Jansen FW, Koivusalo AM, Lacy A, McMahon MJ, Millat B, Schwenk W (2002) The European Association for Endoscopic Surgery clinical practice guideline on the pneumoperitoneum for laparoscopic surgery. Surg Endosc 16:11211143
  8. Neugebauer AM, Becker M, Buess GF, Cuschieri A, Dauben HP, Fingerhut A, Fuchs KH, Habermalz B, Lantsberg L, Morino M, Reiter-Theil S, Soskuty G, Wayand W, Welsch T (2010) EAES recommendations on methodology of innovation management in endoscopic surgery. Surg Endosc 24:15941615
  9. Center for Evidence Based Medicine, University of Oxford (2011) Level of Evidence, Oxford criteria. www,cebm,net. Accessed 10 Oct 2013
  10. Savary M, Miller G (1977) Der Osophagus. Gassmann Verlag, Solothurn, Switzerland
  11. LundellLR, Dent J, Bennett JR, Blum AL, Armstrong D, Galmiche JP, Johnson F, Hongo M,Richter JE, Spechler SJ et al (1999) Endoscopic assessment of oesophagitis:clinical and functional correlates and further validation of the Los Angelesclassification. Gut 45:172180
  12. Savarino E, Zentilin P, Savarino V (2013) NERD: an umbrella term including heterogeneous subpopulations. Nat Rev Gastroenterol Hepatol 10:371380
  13. Zentilin P, Savarino V, Mastracci L, Spaggiari P, Dulbecco P, Ceppa P, Savarino E, Parodi A, Mansi C, Fiocca R (2005) Reassessment of the diagnostic value of histology in patients with GERD, using multiple biopsy sites and an appropriate control group. Am J Gastroenterol 100(10):22992306
  14. DeMeester TR (1987) Definition, detection and pathophysiology of gastroesophageal reflux disease. In: DeMeester TR, Matthews HR (eds) International trends in general thoracic surgery. Benign esophageal disease, vol 3. Mosby, St. Louis, pp 99127
  15. Zaninotto G, DeMeester TR, Schwizer W, Johansson KE, Cheng SC (1988) The lower esophageal sphincter in health and disease. Am J Surg 155:104111
  16. Kuster E, Ros E, Toledo-Pimentel V, Pujol A, Bordas JM, Grande IC (1994) Predictive factors of the long term outcome in gastro-oesophageal reflux disease: six year follow up of 107 patients. Gut 35(1):814
  17. Fuchs KH, Freys SM, Heimbucher J, Fein M, Thiede A (1995) Pathophysiologic spectrum in patients with gastroesophageal reflux disease in a surgical GI function laboratory. Dis Esophagus 8:211217
  18. Fein M, Ireland AP, Ritter MP, Peters JH, Hagen JA, Bremner CG, DeMeester TR (1997) Duodenogastric reflux potentiates the injurious effects of gastroesophageal reflux. J Gastrointest Surg 1:2733
  19. Lord RV, DeMeester SR, Peters JH, Hagen JA, Elyssnia D, Sheth CT, DeMeester TR (2009) Hiatal hernia, lower esopha-geal sphincter incompetence, and effectiveness of nissen fundoplication in the spectrum of gastroesophageal reflux disease. J Gastrointest Surg 13:602610
  20. Fein M, Ritter M, DeMeester TR, Oberg S, Peters JH, Hagen JA, Bremner CG (1999) Role of lower esophageal sphincter and hiatal hernia in the pathogenesis of GERD. J Gastrointest Surg 3(4):405410
  21. Mattioli S, Lugaresi ML, Costantini M, Del Genio A, Di Mar-tino N, Fei L, Fumagalli U, Maffettone V, Monaco L, Morino M, Rebecchi F, Rosati R, Rossi M, Sant S, Trapani V, Zaninotto G (2008) The short esophagus: intraoperative assessment of esophageal length. J Thorac Cardiovasc Surg 136:1610
  22. El-Serag H, Hill C, Jones R (2009) Systematic review: the epidemiology of gastro-oesophageal reflux disease in primary care, using the UK General Practice Research Database. Aliment Pharmacol Ther 29:470480
  23. Dent J, El-Serag HB, Wallander MA, Johansson S (2005) Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 54:710717
  24. Ruigomez A, Garcia Rodrıguez LA, Wallander MA, Johansson S, Graffner H, Dent J (2004) Natural history of gastro-oesoph-ageal reflux disease diagnosed in general practice. Aliment Pharmacol Ther 20:751760
  25. Malfertheiner P, Nocon M, Vieth M, Stolte M, Jaspersen D, Koelz HR, Labenz J, Leodolter A, Lind T, Richter K, Willich SN (2012) Evolution of gastro-oesophageal reflux disease over 5 years under routine medical carethe ProGERD study. Aliment Pharmacol Ther 35(1):15416
  26. Rantanen TK, Salo JA (1999) GERD as a cause of death: analysis of fatal cases under conservative therapy. Scand J Gastroenterol 34(3):229233
  27. Kahrilas PJ, Spiess AE (1992) Hiatus hernia. In: Castell DO, Richter J (eds) The Esophagus, 3rd edn. Lippincott Williams & Wilkins, Philadelphia, p 381
  28. Jones MP, Sloan SS, Rabine JC (2001) Hiatal hernia size is the dominant determinant of esophagitis presence and severity in gastroesophageal reflux disease. Am J Gastroenterol 96:17111717
  29. Stylopoulos N, Rattner DW (2005) The history of hiatal hernia surgery: from Bowditch to laparoscopy. Ann Surg 241:185193
  30. Hill LD (1994) The gastroesophageal flap valve: in vitro and in vivo observations. Gastrointest Endosc 44:541
  31. Kamolz T, Granderath Pointner R (2003) Laparoscopic antireflux surgery: disease-related quality of life assessment before and after surgery in GERD patients with and without Barretts esophagus. Surg Endosc 17:880885
  32. Oelschlager BK, Pellegrini CA, Hunter J, Soper N, Brunt M, Sheppard B, Jobe B, Polissar N, Mitsumori L, Nelson J, Swanstrom L (2006) Biologic prosthesis reduces recurrence after laparoscopic paraesophageal hernia repair: a multicenter, prospective, randomized trial. Ann Surg 244:481490
  33. Granderath FA, Carlson MA, Champion JK, Szold A, Basso N, Pointner R, Frantzides CT (2006) Prosthetic closure of the esophageal hiatus in large hiatal hernia repair and laparoscopic antireflux surgery. Surg Endosc 20:367379
  34. Shamiyeh A, Szabo K, Granderath FA, Syre´ G, Wayand W, Zehetner J (2010) The esophageal hiatus: what is the normal size? Surg Endosc 24(5):988
  35. Granderath FA (2007) Measurement of the esophageal hiatus by calculation of the hiatal surface area (HSA). Why, when and how? Surg Endosc 21:22242225
  36. Klauser AG, Schindlbeck NE, Mu¨ller-Lissner SA (1990) Symptoms in gastroesophageal reflux disease. Lancet 335:205208
  37. Costantini M, Crookes PF, Bremner RM, Hoeft SF, Ehsan A, Peters JH, Bremner CG, DeMeester TR (1993) Value of physiologic assessment of foregut symptoms in a surgical practice. Surgery 114(4):780786
  38. Fuchs KH, Ulbricht F, Breithaupt W, Reinisch A, Schulz T, Varga G, Babic B, Musial F (2014) Differentiation between GERD and somatoform disorders in patients with foregut symptoms. Dis Esophagus (in preparation)
  39. Savarino E, Zentilin P, Tutuian R, Pohl D, Casa DD, Frazzoni M, Cestari R, Savarino V (2008) The role of nonacid reflux in NERD: lessons learned from impedance-pH monitoring in 150 patients off therapy. Am J Gastroenterol 103(11): 26852693
  40. Vela MF, Camacho-Lobato L, Srinivasan R, Tutuian R, Katz PO, Castell DO (2001) Simultaneous intraesophageal impedance and pHmeasurement ofacid and nonacid gastroesophageal reflux: effect of omeprazole. Gastroenterology 120(7):15991606
  41. Tack J, Caenepeel P, Arts J, Lee KJ, Sifrim D, Janssens J (2005) Prevalence of acid reflux functional dyspepsia and its association with symptom profile. Gut 54(10):13701376
  42. Oustamanolakis P, Tack J (2012) Dyspepsiaorgan versus functional. J Clin Gastroenterol 46:175190
  43. Kahrilas PJ, Jonsson A, Denison H, Wernerson B, Hughes N, Howden CW (2012) Concomitant symptoms itemized in the Reflux Disease Questionnaire are associated with attenuated heartburn response to acid suppression. Am J Gastroenterol 107(9):13541360
  44. Mearin F, Ponce J, Ponce M, Balboa A, Go´nzalez MA, Zapardiel J (2012) Frequency and clinical implications of supra-esophageal and dyspeptic symptoms in gastroesophageal reflux disease. Eur J Gastroenterol Hepatol 24(6):665674
  45. Savarino E, Pohl D, Zentilin P, Dulbecco P, Sammito G, Sconfienza L, Vigneri S, Camerini G, Tutuian R, Savarino V (2009) Functional heartburn has more in common with functional dyspepsia than with non-erosive reflux disease. Gut 58(9):11851191
  46. Gasiorowska A, Poh CH, Fass R (2009) Gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) is it one disease or an overlap of two disorders? Dig Dis Sci 54(9):18291834
  47. Savarino V, Savarino E, Parodi A, Dulbecco P (2007) Functional heartburn and non-erosive reflux disease. Dig Dis 25(3):172174 (review)
  48. Grande M, Sileri P, Attina` GM, Villa M, de Luca E, Ciano P, Ciangola CI, Cadeddu F (2012) Nonerosive gastroesophageal reflux disease and mild degree of esophagitis: comparison of symptoms, endoscopic, manometric and pH-metric patterns. World J Surg Oncol 10:84
  49. Zerbib F, Belhocine K, Simon M, Capdepont M, Mion F, Bruley des Varannes S, Galmiche JP (2012) Clinical, but not oesoph-ageal pH-impedance, profiles predict response to proton pump inhibitors in gastro-oesophageal reflux disease. Gut 61(4):501506
  50. Lee JH, Park SY, Cho SB, Lee WS, Park CH, Koh YI, Joo YE, Kim HS, Choi SK, Rew JS (2012) Reflux episode reaching the proximal esophagus are associated with chronic cough. Gut Liver 6(2):197202
  51. Roberts JR, Aravapalli A, Pohl D, Freeman J, Castell DO (2012) Extraesophageal gastroesophageal reflux disease (GERD) symptoms are not more frequently associated with proximal esophageal reflux than typical GERD symptoms. Dis Esophagus 25(8):678681
  52. Agrawal A, Roberts J, Sharma N, Tutuian R, Vela M, Castell DO (2009) Symptoms with acid and nonacid reflux may be produced by different mechanisms. Dis Esophagus 22(5):467470
  53. Kahrilas PJ, Jonsson A, Denison H, Wernersson B, Hughes N, Howden CW (2012) Regurgitation is less responsive to acid suppression than heartburn in patients with gastroesophageal reflux disease. Clin Gastroenterol Hepatol 10(6):612619
  54. Ours TM, Kavuru MS, Schilz RJ, Richter JED (1999) A prospective evaluation of esophageal testing and a double-blind, randomized study of omeprazole in a diagnostic and therapeutic algorithm for chronic cough. Am J Gastroenterol 94:31313138
  55. Kiljander TO, Salomaa ER, Hietanen EK, Terho EO (2000) Chronic cough and gastro-esophageal reflux: A double-blind placebo-controlled study with omeprazole. Eur Respir J 16:633638
  56. Allen CJ, Anvari M (1998) Gastro-esophageal reflux related cough and its response to laparoscopic fundoplication. Thorax 53:963968
  57. Kamel PL, Hanson D, Kahrilas PJ (1994) Prospective trial of omeprazole in the treatment of posterior laryngitis. Am J Med 96:321326
  58. El-Serag HB, Lee P, Buchner A et al (2001) Lansoprazole treatment of patients with chronic idiopathic laryngitis: A placebo-controlled trial. Am J Gastroenterol 96:979983
  59. Sontag SJ, OConnell S, Khandelwal S et al (2003) Asthmatics with gastro-esophageal reflux: Long term results of a randomized trial of medical and surgical antireflux therapies. Am J Gastroenterol 98:987999
  60. Field SK, Sutherland LR (1998) Does medical antireflux therapy improve asthma in asthmatics with gastroesophageal reflux? A critical review of the literature. Chest 114:275283
  61. Munoz JV, Herreros B, Sanchiz V et al (2003) Dental and periodontal lesions in patients with gastro-esophageal reflux disease. Dig Liver Dis 35:461467
  62. Weaver EM (2003) Association between gastro-esophageal reflux and sinusitis, otitis media, and laryngeal malignancy: a systematic review of the evidence. Am J Med 115:81S89S
  63. Groen JN, Smout AJ (2003) Supra-oesophageal manifestations of gastro-esophageal reflux disease. Eur J Gastroenterol Hepatol 15:13391350
  64. Savarino E, Bazzica M, Zentilin P, Pohl D, Parodi A, Cittadini G, Negrini S, Indiveri F, Tutuian R, Savarino V, Ghio M (2009) Gastroesophageal reflux and pulmonary fibrosis in scleroderma: a study using pH-impedance monitoring. Am J Respir Crit Care Med 179(5):408413
  65. Savarino E, Carbone R, Marabotto E, Furnari M, Sconfienza L, Ghio M, Zentilin P, Savarino V (2013) Gastro-oesophageal reflux and gastric aspiration in idiopathic pulmonary fibrosis patients. Eur Respir J 42(5):13221331
  66. Katz PO, Gerson LB, Vela MF (2013) Guidelines for the diagnosis and management ofgastroesophageal reflux disease. Gastroenterology 108:308328
  67. Smith JA, Decalmer S, Kelsall A et al (2010) Acoustic cough-reflux associations in chronic cough: potential triggers and mechanisms. Gastroenterology 139:754762
  68. Pacheco-Galvan A, Hart SP, Morice AH (2011) Relationship between gastro-oesophageal reflux and airway diseases: the airway reflux paradigm. Arch Broncopneumol 47:195203
  69. Ayazi S, Hagen JA, Zehetner J et al (2010) Proximal esophageal pH monitoring: improved definition of normal values and determination of a composite pH score. J Am Coll Surg 210:345350
  70. Chang AB, Lasserson TJ, Gaffney J et al (2011) Gastro-oesoph-ageal reflux treatment for prolonged non-specific cough in children and adults. Cochrane Database Syst Rev 1:CD004823
  71. Dallemagne B, Weertz J, Markiewicz S, Dewandre JM, Wahlen C, Monami B, Jehaes C (2006) Clinical results of laparoscopic fundoplication ten years after surgery. Surg Endosc 20:159165
  72. Fein M, Bueter M, Thalheimer A, Pachmayer V, Heimbucher J, Freys SM, Fuchs KH (2008) Ten year outcome of laparoscopic antireflux procedures. J Gastrointest Surg 12:18931899
  73. Martinez SD, Malagon I, Garewal HS et al (2003) Non-erosive reflux disease (NERD)acid reflux and symptom patterns. Aliment Pharmacol Ther 17:537545
  74. Savarino E, Zentilin P, Mastracci L, Dulbecco P, Marabotto E, Gemignani L, Bruzzone L, de Bortoli N, Frigo AC, Fiocca R, Savarino V (2013) Microscopic esophagitis distinguishes patients with non-erosive reflux disease from those with functional heartburn. J Gastroenterol 48:473482
  75. Zerbib F, des Varannes SB, Roman S, Pouderoux P, Artigue F, Chaput U, Mion F, Caillol F, Verin E, Bommelaer G, Ducrotte´ P, Galmiche JP, Sifrim D (2005) Normal values and day-to-day variability  of  24-h  ambulatory  oesophageal  impedance-pH monitoring in a Belgian-French cohort of healthy subjects. Aliment Pharmacol Ther 22(10):10111021
  76. Zerbib F, Roman S, Ropert A, des Varannes SB, Pouderoux P, Chaput U, Mion F, Ve´rin E, Galmiche JP, Sifrim D (2006) Esophageal pH-impedance monitoring and symptom analysis in GERD: a study in patients off and on therapy. Am J Gastroen-terol 101(9):19561963
  77. Mainie I, Tutuian R, Shay S, Vela M, Zhang X, Sifrim D, Castell DO (2006) Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy: a multi-centre study using combined ambulatory impedance-pH monitoring. Gut 55(10):13981402
  78. Bredenoord AJ, Weusten BL, Timmer R, Smout AJ (2006) Characteristics of gastro-esophageal reflux in symptomatic patients with and without excessive esophageal acid exposure. Am J Gastroenterol 101:24702475
  79. Hemmink GJ, Bredenoord AJ, Weusten BL, Monkelbaan JF, Timmer R, Smout AJ (2008) Esophageal pH-impedance monitoring in patients with therapy-resistant reflux symptoms: on or off proton pump inhibitor? Am J Gastroenterol 103(10):24462453
  80. Kahrilas PJ, Sifrim D (2008) High-resolution manometry and impedance-pH/manometry: valuable tools in clinical and investigational esophagology. Gastroenterology 135(3):756769
  81. Savarino E, Tutuian R, Zentilin P, Dulbecco P, Pohl D, Mar-abotto E, Parodi A, Sammito G, Gemignani L, Bodini G, Sa-varino V (2010) Characteristics of reflux episodes and symptom association in patients with erosive esophagitis and nonerosive reflux disease: study using combined impedance-pH off therapy. Am J Gastroenterol 105:10531061
  82. Savarino E, Marabotto E, Zentilin P (2011) The added value of impedance-pH monitoring to Rome III criteria in distinguishing functional heartburn from non-erosive reflux disease. Dig Liver Dis 43:542547
  83. Broeders JA, Draaisma WA, Bredenoord AJ, Smout AJ, Broe-ders IA, Gooszen HG (2011) Impact of symptom-reflux-association analysis on long-term outcome after Nissen fundoplication. Br J Surg 98:247254
  84. Slaughter JC, Goutte M, Rymer JA, Oranu AC, Schneider JA, Garrett CG, Hagaman D, Vaezi MF (2011) Caution about overinterpretation of symptom indexes in reflux monitoring for refractory GERD. Clin Gastroenterol Hepatol 9(19):868874
  85. Campos GM, Peters JH, DeMeester TR et al (1999) Multivariate analysis of factors predicting outcome after laparoscopic Nissen fundoplication. J Gastrointest Surg 3(3):292300
  86. Stein HJ, Barlow AP, DeMeester TR, Hinder RA (1992) Complications of gastroesophageal reflux disease. Role of the lower esophageal sphincter, esophageal acid and acid/alkaline exposure, and duodenogastric reflux. Ann Surg 216(1):3543
  87. Raman A, Steinbach J, Babajide A, Sheth K, Schwaitzberg S (2010) When does testing for GERD become cost effective in an integrated health network? Surg Endosc 24:12451249
  88. Savarino E, Gemignani L, Pohl D, Zentilin P, Dulbecco P, Assandri L, Marabotto E, Bonfanti D, Inferrera S, Fazio V, Malesci A, Tutuian R, Savarino V (2011) Oesophageal motility and bolus transit abnormalities increase in parallel with the severity of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 34(4):476486
  89. Kessing BF, Bredenoord AJ, Smout AJ (2011) Erroneous diagnosis of gastroesophageal reflux disease in achalasia. Clin Gastroenterol Hepatol 9(12):10201024
  90. Ang D, Ang TL, Teo EK, Hsu PP, Tee A, Poh CH, Tan J, Ong J, Fock KM (2011) Is impedance pH monitoring superior to the conventional 24-h pH-monitoring in the evaluation of patients with laryngorespiratory symptoms suspected to be due to gastroesophageal reflux disease? J Dig Dis 12:341348
  91. de Bortoli N, Nacci A, Savarino E, Martinucci I, Bellini M, Fattori B, Ceccarelli L, Costa F, Mumolo MG, Ricchiuti A, Savarino V, Berrettini S, Marchi S (2012) How many cases of laryngopharyngeal reflux suspected by laryngoscopy are gas-troesophageal reflux disease-related? World J Gastroenterol 18(32):43634370
  92. Chan WW, Haroian LR, Gyawali CP (2011) Value of preoperative esophageal function studies before laparoscopic antireflux surgery. Surg Endosc 25:29432949
  93. Tack J, Koek G, Demedts I, Sifrim D, Janssens J (2004) Gastroesophageal reflux disease poorly responsive to single-dose proton pump inhibitors in patients without Barretts esophagus: acid reflux, bile reflux, or both? Am J Gastroenterol 99:981988
  94. Fein M, Maroske J, Fuchs KH (2006) Importance of duode-nogastric reflux in gastro-oesophageal reflux disease. Br J Surg 93(12):14751482
  95. Wayman J, Myers JC, Jamieson GG (2007) Preoperative gastric emptying and patterns of reflux as predictors of outcome after laparoscopic fundoplication. Br J Surg 94(5):592598
  96. DeVaultKR, Castell DO, American College of Gastroenterology (2005) Updated guidelinesfor the diagnosis and treatment of gastroesophageal reflux disease. Am JGastroenterol 100(1):190200
  97. Revicki DA, Crawley JA, Zodet MW, Levine DS, Joelsson BO (1999) Complete resolution of heartburn symptoms and health-related quality of life in patients with GERD. Aliment Pharmacol Ther 13(12):16211630
  98. Mathias SD, Colwell HH, Miller DP, Pasta DJ, Henning JM, Ofman JJ (2001) Health-related quality-of-life and quality-days incrementally gained in symptomatic nonerosive GERD patients treated with lansoprazole or ranitidine. Dig Dis Sci 46(11):24162423
  99. Savarino V, Dulbecco P (2004) Optimizing symptom relief and preventing complications in adults with gastro-oesophageal reflux disease. Digestion 69(Suppl 1):916
  100. Becher A, El-Serag H (2011) Systematic review: the association between symptomatic response to proton pump inhibitors and health-related quality of life in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther 34(6):618627
  101. Lind T, Havelund T, Carlsson R et al (1997) Heartburn without esophagitis: efficacy of omeprazole therapy and features determining therapeutic response. Scand J Gastroenterol 32:974979
  102. Kitchin LI, Castell DO (1991) Rationale and efficacy of conservative therapy for gastroesophageal reflux disease. Arch Intern Med 151(3):448454
  103. Harvey RF, Gordon PC, Hadley N, Long DE, Gill TR, Mac-pherson RI (1987) Effects of sleeping with the bed-head raised and of ranitidine in patients with severe peptic oesophagitis. Lancet 2:12001203
  104. El-Serag H (2008) Role of obesity in GORD-related disorders. Gut 57:281284
  105. Savarino E, Zentilin P, Marabotto E, Bonfanti D, Inferrera S, Assandri L, Sammito G, Gemignani L, Furnari M, Dulbecco P, Savarino V (2011) Overweight is a risk factor for both erosive and non-erosive reflux disease. Dig Liver Dis 43(12):940945
  106. Pace F, Coudsy B, DeLemos B et al (2011) Does BMI affect the clinical efficacy of proton pump inhibitor therapy in GERD? The case for rabeprazole. Eur J Gastroenterol Hepatol 23(10):845851
  107. Maton PN, Burton ME (1999) Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use. Drugs 57:855870
  108. Zentilin P, Dulbecco P, Savarino E, Parodi A, Iiritano E, Bilardi C, Reglioni S, Vigneri S, Savarino V (2005) An evaluation of the antireflux properties of sodium alginate by means of combined multichannel intraluminal impedance and pH-metry. Aliment Pharmacol Ther 21:2934
  109. Giannini EG, Zentilin P, Dulbecco P, Iiritano E, Bilardi C, Savarino E, Mansi C, Savarino V (2006) A comparison between sodium alginate and magaldrate anhydrous in the treatment of patients with gastroesophageal reflux symptoms. Dig Dis Sci 51:19041909
  110. Kwiatek MA, Roman S, Fareeduddin A, Pandolfino JE, Kahrilas PJ (2011) Analginate-antacid formulation (Gaviscon Double Action Liquid) can eliminate ordisplace the postprandial acid pocket in symptomatic GERD patients. AlimentPharmacol Ther 34:5966
  111. Savarino E, de Bortoli N, Zentilin P, Martinucci I, Bruzzone L, Furnari M, Marchi S, Savarino V (2012) Alginate controls heartburn in patients with erosive and nonerosive reflux disease. World J Gastroenterol 18(32):43714378
  112. DeVault KR, Castell DO (1995) Guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Practice Parameters Committee of the American College of Gastroenterology. Arch Intern Med 155(20):21652173
  113. Chiba N, De Gara CJ, Wilkinson JM, Hunt RH (1997) Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology 112(6):17981810
  114. Mainie I, Tutuian R, Castell DO (2008) Addition of a H2 receptor antagonist to PPI improves acid control and decreases nocturnal acid breakthrough. J Clin Gastroenterol 42(6):676679
  115. Qvigstad G, Arnestad JS, Brenna E, Waldum HL (1998) Treatment with proton pump inhibitors induces tolerance to histamine-2 receptor antagonists in Helicobacter pylori-negative patients. Scand J Gastroenterol 33:12441248
  116. Vigneri S, Termini R, Leandro G, Badalamenti S, Pantalena M, Savarino V, Di Mario F, Battaglia G, Mela GS, Pilotto A et al (1995) A comparison of five maintenance therapies for reflux esophagitis. N Engl J Med 333(17):11061110
  117. Galmiche JP, Hatlebakk J, Attwood S, Ell C, Fiocca R, Eklund S, La˚ngstro¨m G, Lind T, Lundell L, LOTUS Trial Collaborators (2011) Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: the LOTUS randomized clinical trial. JAMA 305(19):19691977
  118. Chen J, Yuan JC, Leontiadis GI, Howden CW (2012) Recent safety concerns with proton pump inhibitors. J Clin Gastroen-terol 46:93114
  119. Savarino V, Di Mario F, Scarpignato C (2009) Proton pump inhibitors in GORD: an overview of their pharmacology, efficacy and safety. Pharmacol Res 59(3):135153
  120. Edwards SJ, Lind T, Lundell L (2001) Systematic review of proton pump inhibitors for the acute treatment of reflux oesophagitis. Aliment Pharmacol Ther 15:17291736
  121. Castell DO, Kahrilas PJ, Richter JE, Vakil NB, Johnson DA, Zuckerman S et al (2002) Esomeprazole (40 mg) compared with lansoprazole (30 mg) in the treatment of erosive esophagitis. Am J Gastroenterol 97:575583
  122. Dekkers CP, Beker JA, Thjodleifsson B, Gabryelewicz A, Bell NE, Humphries TJ (1999) Double-blind comparison [correction of double-blind, placebo-controlled comparison] of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of erosive or ulcerative gastro-oesophageal reflux disease. The European Rabeprazole Study Group. Aliment Pharmacol Ther 13(1): 4957
  123. Hatlebakk JG, Katz PO, Camacho-Lobato L, Castell DO (2000) Proton pump inhibitors: better acid suppression when taken before a meal than without a meal. Aliment Pharmacol Ther 14(10):12671272
  124. 124. van Rensburg CJ, Honiball PJ, Grundling HD, van Zyl JH, Spies SK, Eloff FP, Simjee AE, Segal I, Botha JF, Cariem AK, Marks IN, Theron I, Bethke TD (1996) Efficacy and tolerability of pantoprazole 40 mg versus 80 mg in patients with reflux oesophagitis. Aliment Pharmacol Ther 10(3):397401
  125. Fass R, Murthy U, Hayden CW, Malagon IB, Pulliam G, Wendel C, Kovacs TO (2000) Omeprazole 40 mg once a day is equally effective as lansoprazole 30 mg twice a day in symptom control of patients with gastro-oesophageal reflux disease (GERD) who are resistant to conventional-dose lansoprazole therapy - a prospective, randomized, multi-centre study. Aliment Pharmacol Ther 14(12):15951603
  126. Frazzoni M, De Micheli E, Grisendi A, Savarino V (2003) Effective intra-oesophageal acid suppression in patients with gastro-oesophageal reflux disease: lansoprazole vs. pantoprazole. Aliment Pharmacol Ther 17(2):235241
  127. Katzka DA, Paoletti V, Leite L, Castell DO (1996) Prolonged ambulatory pH monitoring in patients with persistent gastro-esophageal reflux disease symptoms: testing while on therapy identifies the need for more aggressive anti-reflux therapy. Am J Gastroenterol 91(10):21102113
  128. Lundell L, Miettinen P, Myrvold HE, Pedersen SA, Thor K, Lamm M, Blomqvist A, Hatlebakk JG, Janatuinen E, Levander K, Nystro¨m P, Wiklund I (2000) Long-term management of gastro-oesophageal reflux disease with omeprazole or open an-tireflux surgery: results of a prospective, randomized clinical trial. The Nordic GORD Study Group. Eur J Gastroenterol Hepatol 12(8):879887
  129. Sifrim D, Zerbib F (2012) Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors. Gut 61(9):13401354
  130. Savarino E, Marabotto E, Zentilin P, Frazzoni M, Sammito G, Bonfanti D, Sconfienza L, Assandri L, Gemignani L, Malesci A, Savarino V (2011) The added value of impedance-pH monitoring to Rome III criteria in distinguishing functional heartburn from non-erosive reflux disease. Dig Liver Dis 43(7):542547
  131. Brogden RN, Carmine AA, Heel RC, Speight TM, Avery GS (1982) Domperidone. A review of its pharmacological activity, pharmacokinetics and therapeutic efficacy in the symptomatic treatment of chronic dyspepsia and as an antiemetic. Drugs 24(5):360400 (review)
  132. Ganzini L, Casey DE, Hoffman WF, McCall AL (1993) The prevalence of metoclopramide-induced tardive dyskinesia and acute extrapyramidal movement disorders. Arch Intern Med 153(12):14691475
  133. Metha S, Bennett J, Mahon D, Rhodes M (2006) Prospective trial of laparoscopic Nissen fundoplication versus proton pump inhibitor therapy for gastroesophageal reflux disease: seven-year follow-up. J Gastrointest Surg 10(9):13121317
  134. Anvari M, Allen C, Marshall J, Armstrong D, Goree R, Ungar W, Goldsmith C (2011) A randomized controlled trial of lapa-roscopic Nissen fundoplication versus proton pump inhibitors for the treatment of patients with chronic gastrooesophageal reflux disease (GERD): 3 year outcomes. Surg Endosc 25(8):25472554
  135. Faria R, Bojke L, Epstein D, Corbacho B, Sculpher M on behalf of the REFLUX trial group (2013) Cost effectiveness of laparoscopic fundoplication versus continued medical management for the treatment of GERD based on long-term follow-up of the REFLUX trial. Br J Surg 100:12051213
  136. Wileman SM, McCann S, Grant AM, Krukowski ZH, Bruce J (2010) Medical versus surgical management for GERD in adults. Cochrane Database Syst Rev 3:CD003243
  137. Frazzoni M, Piccoli M, Conigliaro R, Manta R, Frazzoni L, Melotti G (2013) Refractory gastroesophageal reflux disease as diagnosed by impedance-pH monitoring can be cured by laparoscopic fundoplication. Surg Endosc 27(8):29402946
  138. Broeders JA, Bredenoord AJ, Hazebroek EJ, Broeders IA, Gooszen HG, Smout AJ (2011) Effects of anti-reflux surgery on weakly acidic reflux and belching. Gut 60(4):435441
  139. Rydberg L, Ruth M, Abrahamsson H, Lundell L (1999) Tailoring antireflux surgery: a randomized clinical trial. World J Surg 23:612618
  140. Fibbe C, Layer P, Keller J, Strate U, Emmermann A, Zornig C (2001) Esophageal motility in reflux disease before and after fundoplication: a prospective, randomized, clinical, and manometric study. Gastroenterology 121:514
  141. Strate U, Emmermann A, Fibbe C, Layer P, Zornig C (2008) Laparoscopic fundoplication: Nissen versus Toupet two-year outcome of prospective randomized study of 200 patients regarding preoperative esophaegal motility. Surg Endosc 22:2130
  142. Novitsky YW, Wong J, Kercher KW, Litwin DE, Swanstrom LL, Heniford BT (2007) Severely disordered esophageal peristalsis is not a contraindication to laparoscopic Nissen fundo-plication. Surg Endosc 21:950954
  143. Watson DI, Jamieson GG, Bessell JR, Devitt PG (2006) Laparoscopic fundoplication in patients with an aperistaltic esophagus and gastroesophageal reflux. Dis Esophagus 19:9498
  144. Broeders JA, Sportel IG, Jamieson GG, Nijjar RS, Granchi N, Myers JC, Thompson SK (2011) Impact of ineffective oesophageal motility and wrap type on dysphagia after laparoscopic fundoplication. Br J Surg 98:14141421
  145. Pizza F, Rosetti G, Del Genio G, Maffettone V, Brusciano L, Del Genio A (2008) Influence of esophageal motility in the outcome of laparoscopic total fundoplication. Dis Esophagus 21:7885
  146. Broeders JA, Draaisma WA, Bredenoord AJ, Smout AJ, Broeders IA, Gooszen HG (2010) Long-term outcome of Nissen fundoplication in non-erosive and erosive gastro-oesophageal reflux disease. Br J Surg 97:845852
  147. Broeders JA, Draaisma WA, Bredenoord AJ, de Vries DR, Ri-jnhart-de Jong HG, Smout AJ, Gooszen HG (2009) Oesophageal acid hypersensitivity is not a contraindication to Nissen fundoplication. Br J Surg 96(9):10231030
  148. Allen CJ, Anvari M (2004) Does laparoscopic fundoplication provide long-term control of GERD related cough? Surg Endosc 18(4):633637
  149. Mainie I, Tutuian R, Agrawal A et al (2006) Combined multi-channel-intraluminal impedance-pH monitoring to select patients with persistent gastro-oesophageal reflux for laparo-scopic Nissen fundoplication. Br J Surg 93:14831487
  150. Kaufmann JA, Houghland JE, Quiroga E, Cahill M, Pellegrini CA, Oelschlager BK (2006) Long-term outcomes of laparo-scopic antireflux surgery for gastroesophageal reflux disease (GERD)-related airway disorder. Surg Endosc 20:18241830
  151. Catania RA, Kavic SM, Roth S, Lee TH, Meyer T, Fantry GT, Castellanos PF, Park A (2007) Laparoscopic Nissen fundopli-cation effectively relieves symptoms in patient with laryngo-pharyngeal reflux. J Gastrointest Surg 11:15791588
  152. Salminen P, Sala E, Koskenvuo J, Karvonen J, Ovaska J (2007) Reflux laryngitis: a feasible indication for laparoscopic antire-flux surgery. Surg Laparosc Endosc Percutan Tech 17:7378
  153. Barry DW, Vaezi MF (2010) Laryngopharyngeal reflux: more questions than answers. Cleve Clin J Med 77:327334
  154. 154. Zainabadi K, Courcoulas AP, Awais O, Raftopoulos I (2008) Laparoscopic revision of Nissen fundoplication to Roux-en-Y gastric bypass in morbidly obese patients. Surg Endosc 22(12):27372740
  155. Braghetto I, Korn O, Csendes A, Gutierrez L, Valladares H, Chacon M (2012) Laparoscopic treatment of obese patients with GERD and Barretts esophagus: a prospective study. Obes Surg 22(5):764772
  156. Nissen R (1956) Eine einfache operation zur Beeinflussung des Refluxösophagitis. Schweiz Med Wschr 86:590
  157. DeMeester TR, Bonavina L, Albertucci M (1986) Nissen fundoplication for gastroesophageal reflux disease. Evaluation of primary repair in 100 consecutive patients. Ann Surg 204(1):9-20
  158. Katkhouda N, Khalil N, Manhas S, Grant S, Velmahos GC, Umbach TW, Kaiser AM (2002) Andre Toupet: surgeon technician par excellence. Ann Surg 235:591-599
  159. Watson DI, Jamieson GG, Pike GK, Davies N, Richardson M, Devitt PG (1999) Prospective randomized double blind trial between laparoscopic Nissen fundoplication and anterior partial fundoplication. Br J Surg 86:123-130
  160. Zornig C, Strate U, Fibbe C, Emmermann A, Layer P (2002) Nissen vs Toupet laparoscopic fundoplication. Surg Endosc 16(5):758-766
  161. Laws HL, Clements RH, Swillie CM (1997) A randomized, prospective comparison of the Nissen fundoplication versus the Toupet fundoplication for gastroesophageal reflux disease. Ann Surg 225(6):647-653
  162. Watson DI, Jamieson GG, Ludemann R, Game PA, Devitt PG
  163. (2004)  Laparoscopic total versus anterior 180 degree fundoplication - Five year follow-up of a prospective randomised trial. Dis Esophagus 17(Suppl 1):A81 Ludemann R, Watson DI, Jamieson GG, Game PA, Devitt PG (2005)  Five-year follow up of a randomized clinical trial of laparoscopic total versus anterior 180 degrees fundoplication. Br J Surg 92(2):240-243
  164. Baigrie RJ, Cullis SN, Ndhluni AJ, Cariem A (2005) Randomized double-blind trial of laparoscopic Nissen fundoplication versus anterior partial fundoplication. Br J Surg 92:819-823
  165. Spence GM, Watson DI, Jamieson GG, Lally CJ, Devitt PG (2006)   Single center prospective randomized trial of laparoscopic Nissen versus anterior 90 degrees fundoplication. J Gas-trointest Surg 10:698-705
  166. Engstrom C, Lonroth H, Mardani, Lundell L (2007) An anterior or posterior approach to partial fundoplication? Long-term results of a randomized trial. World J Surg 31(6):1221-1225
  167. Guerin E, Betroune K, Closset J, Mehdi A, Lefebre JC, Houben JJ, Gelin M, Vaneukem P, El Nakadi I (2007) Nissen versus Toupet fundoplication: results of a randomized and multicenter trial. Surg Endosc 21:1985-1990
  168. Antanas M, Zilvinas E, Mindaugas, Laimas J, Limas K, Almantas M, Juzonas P (2008) Influence of wrap length on the effectiveness of Nissen and Toupet fundoplication: a prospective randomized study. Surg Endosc 22:2269-2276
  169. Booth MI, Stratford J, Jones L, Dehn TC (2008) Randomized clinical trial of laparoscopic Nissen versus posterior partial Toupet fundoplication for GERD based on preoperative manometry. Br J Surg 95:57-63
  170. Strate U, Emmermann A, Fibbe C, Layer P, Zornig (2008) Laparoscopic fundoplication: Nissen versus Toupet two-year outcome of prospective randomized study of 200 patients regarding preoperative esophageal motility. Surg Endosc 22:21-30
  171. Nijjar RS, Watson D, Jamieson GG, Archer S, Bessell JR, Booth M, Cade R, Cullingford GL, Cullingford GL, Devitt PG, Fletcher DR, Hurley J, Kiroff G, Martin JJ, Nathanson LK, Windsor JA, International Society for the Diseases of the Esophagus-Australasian Section (2010) Five-year follow-up of a multicenter, double-blind randomized clinical trial of laparoscopic Nissen vs. anterior 90 partial fundoplication. Arch Surg 145(6):552-557
  172. Shaw JM, Bornmann PC, Callanan MD, Beckingahm IJ, Metz DC (2010) Long-term outcome of laparoscopic Nissen and laparoscopic Toupet fundoplication for gastroesopahgeal reflux disease: a prospective, randomized trial. Surg Endosc 24:924932
  173. Markar SR, Karthikesalingam AP, Wagner OJ, Jackson D, He-wes JC, Vyas S et al (2011) Systematic review and meta-analysis of laparoscopic Nissen fundoplication with or without division of the short gastric vessels. Br J Surg 98:10561062
  174. Koch OO, Kaindlstorfer A, Antoniou SA, Asche KU, Granderath FA, Pointner R (2012) Laparoscopic Nissen versus Toupet fundoplication: objective and subjective results of a prospective randomized trial. Surg Endosc 26(2):413422
  175. Catarci M, Gentileschi P, Papi C, Carrara A, Marrese R, Gaspari AL, Grassi GB (2004) Evidence-based appraisal of antireflux fundoplication. Ann Surg 239:325337
  176. Neufeld M, Graham A (2007) Levels of evidence available for techniques in antireflux surgery. Dis Esophagus 20:161167
  177. Varin O, Velstra B, De Sutter S, Ceelen W (2009) Total vs partial fundoplication in the treatment of gastroesophageal reflux disease: a meta-analysis. Arch Surg 144(3):273278
  178. Davis CS, Baldea A, Johns JR, Joehl RJ, Fisichella PM (2010) The evolution and long-term results of laparoscopic antireflux surgery fort he treatment of gastroesophageal reflux disease. JSLS 14(3):332341
  179. 179. Fein M, Seyfried F (2010) Is there a role for anything other than a Nissen operation? J Gastrointest Surg 14(Suppl 1):S67S74
  180. Broeders JA, Mauritz FA, Ahmed Ali U, Draaisma WA, Ruurda JP, Gooszen HG, Smout AJ, Broeders IA, Hazebroek EJ (2002) Systematic review and meta-analysis of laparoscopic Nissen versus Toupet fundoplication for gastro-esophageal reflux disease. Br J Surg 97:13181330
  181. Tan G, Yang Z, Wang Z (2011) Meta-analysis of laparoscopic total Nissen versus posterior Toupet fundoplication for GERD based on randomized clinical trials. ANZ J Surg 81:246252
  182. Antoniou SA, Antoniou GA, Koch OO, Pointner R, Granderath FA (2012) Lower recurrence rates after mesh-reinforced versus simple hiatal hernia repair: a meta-analysis of randomized trials. Surg Laparosc Endosc Percutan Tech 22(6):498502
  183. Jobe BA, Wallace J, Hansen PD, Swanström LL (1997) Evaluation of laparoscopic Toupet fundoplication as a primary repair for all patients with medically resistant gastroesophageal reflux. Surg Endosc 11:10801083
  184. Horvath KD, Jobe BA, Herron DM, Swanström LL (1999) Laparoscopic Toupet fundoplication is an inadequate procedure for patients with severe reflux disease. J Gastrointest Surg 3:583591
  185. Peters JH, DeMeester TR, Crookes P, Oberg S, de Vos Shoop M, Hagen JA, Bremner CG (1998) The treatment of gastro-esophageal reflux disease with laparoscopic Nissen fundoplication. Ann Surg 228(1):4050
  186. Patti MG, Robinson T, Galvani C, Gorodner MV, Fisichella PM, Way LW (2004) Total fundoplication is superior to partial fundoplication even when esophageal peristalsis is weak. J Am Coll Surg 198:863869
  187. Fuchs KH, Breithaupt W, Fein M, Maroske J, Hammer I (2005) Laparoscopic Nissen repair: Indications, techniques and long term benefits. Langenbecks Arch Surg 390:197202
  188. Morgenthal CB, Shane MD, Stival A, Gletsu N, Milam G, Swafford S, Hunter JG, Smith CD (2007) The durability of laparoscopic Nissen fundoplication: 11-year outcome. J Gastrointest Surg 11:693700
  189. Sgromo B, Irvine L, Cuschieri A (2008) Long-term comparative outcome between laparoscopic total Nissen and Toupet fundo-plication: Symptomatic relief, patient satisfaction and quality of life. Surg Endosc 22:10481053
  190. Oelschlager BK, Petersen RP, Brunt LM, Soper NJ, Sheppard BC, Mitsumori L, Rohrmann C, Swanstrom LL, Pellegrini CA (2012) Laparoscopic paraesophageal hernia repair of large, complicated hiatal hernia. J Gastrointest Surg 16(3):453459
  191. Basso N, Rosato P, De Leo A, Genco A, Rea S, Neri T (1999) Tension-free hiatoplasty, gastrophenic anchorage and 360 degrees fundoplication in the laparoscopic treatment of para-esophageal hernia. Surg Laparosc Endosc Percutan Tech 9(4):257262
  192. Frantzides CT, Madan AK, Carlson MA, Stavropoulos GP (2002) A prospective randomized trial of laparoscopic polytet-rafluoroethylene (PTFE) patch repair vs simple cruroplasty for large hiatal hernia. Arch Surg 137(6):649652
  193. Granderath FA, Schweiger UM, Kamolz T, Asche KU, Pointner R (2005) Laparoscopic Nissen fundoplication with prosthetic hiatal closure reduces postoperative intrathoracic wrap herniation: preliminary results of a prospective randomized functional and clinical study. Arch Surg 140:4048
  194. Granderath FA, Carlson MA, Champion JK, Szold A, Basso N, Pointner R, Frantzides CT (2006) Prosthetic closure of the esophageal hiatus in large hiatal hernia repair and laparoscopic antireflux surgery. Surg Endosc 20:367379
  195. Soricelli E, Basso N, Genco A, Cipriano M (2009) Long-term results of hiatal hernia mesh repair and antireflux laparoscopic surgery. Surg Endosc 23:24992504
  196. Antoniou SA, Antoniou GA, Berger J, Asche U, Pointner R (2012) Lower recurrence rates after mesh-reinforced versus simple hiatal repair: a meta-analysis of randomized trials. Surg Laparosc Endosc Percutan Tech 22:498502
  197. Targarona EM, Bendahan G, Balague C, Garriga J, Trias M (2004) Mesh in the hiatus: a controversial issue. Arch Surg 139(12):12861296
  198. Pallabazzer G, Santi S, Parise P, Solito B, Giusti P, Rossi M (2011) Giant hiatal hernias: direct hiatus closure has an acceptable recurrent rate. Updates Surg 63(2):7581
  199. Tatum RP, Shalhub S, Oelschlager BK, Pellegrini CA (2008) Complications of PTFE mesh at the diaphragmatic hiatus. J Gastrointest Surg 12:953957
  200. Stadlhuber RJ, Sherif AE, Mittal SK, Fitzgibbons RJ, Brunt LM, Hunter JG, DeMeester TR, Swanstrom LL, Smith CD, Filipi CJ (2009) Mesh complications after prosthetic reinforcement of hiatal closure: a 28-case series. Surg Endosc 23:12191226
  201. Parker M, Bowers SP, Bray JM, Harris AS, Belli EV, Pfluke JM, Preissler S, Asbun HJ, Smith CD (2010) Hiatal mesh is associated with major resection at revisional operation. Surg Endosc 24(12):30953101
  202. Swanstrom LL, Marcus DR, Galloway GQ (1996) Laparoscopic Collis gastroplasty is the treatment of choice for the shortened esophagus. Am J Surg 171(5):477481
  203. Gastal OL, Hagen JH, Campos GM, Hashemi M, Theisen J, Bremner CG, DeMeester TR (1999) Short esophagus: analysis of predictors and clinical implications. Arch Surg 134(6):633636
  204. Youssef YK, Shekar N, Lutfi R, Richards WO, Torquati A (2006) Long-term evaluation of patient satisfaction and reflux symptoms after laparoscopic fundoplicatio with Collis gastro-plasty. Surg Endosc 20:17021705
  205. Metha S, Boddy A, Rhodes M (2006) Review of outcome after laparoscopic paraesophageal hiatal hernia repair. Surg Laparosc Endosc Percutan Tech 16(5):301306
  206. Rathore MA, Andrabi SI, Bhatti MI, Najfi SM, McMurray A (2007) Meta-analysis of recurrence after laparoscopic repair of paraesophageal hernia. JSLS 11(4):456460
  207. ORourke RW, Khajanchee YS, Urbach DR, Lee NN, Lockhart B, Hansen PD, Swanstrom LL (2003) Extended transmediastinal dissection: an alternative to gastroplasty for short esophagus. Arch Surg 138(7):735740
  208. Oelschlager BK, Yamamoto K, Woltman T, Pellegrini C (2008) Vagotomy during hiatal hernia repair: a benign esophageal lengthening procedure. J Gastrointest Surg 12(7):11551162
  209. Schiefke I, Zabel-Langhennig A, Neumann S, Feisthammel J, Moessner J, Caca K (2005) Long term failure of endoscopic gastroplication (EndoCinch). Gut 54(6):752758
  210. Triadafilopoulos G, DiBaise JK, Nostrant TT, Stollman NH, Anderson PK, Wolfe MM, Rothstein RI, Wo JM, Corley DA, Patti MG, Antignano LV, Goff JS, Edmundowicz SA, Castell DO, Rabine JC, Kim MS, Utley DS (2002) The Stretta procedure for the treatment of GERD: 6 and 12 months follow-up of the US open-label trial. Gastrointest Endosc 55(2):149156
  211. Schumacher B, Neuhaus H, Ortner M, Laugier R, Benson M, Boyer J, Ponchon T, Hagenmu¨ller F, Grimaud JC, Rampal P, Rey JF, Fuchs KH, Allgaier HP, Hochberger J, Stein HJ, Ar-mengol JA, Siersema PD, Deviere J (2005) Reduced medication dependency and improved symptoms and quality of life 12 months after ENTERYX implantation for GERD. J Clin Gastroenterol 39(3):212219
  212. von Renteln D, Schiefke I, Fuchs KH, Raczynski S, Philipper M, Breithaupt W, Caca K, Neuhaus H (2009) Endoscopic full-thickness plication for the treatment of gastroesophageal reflux disease using multiple plicator implants: 12-month multicenter study results. Surg Endosc 23(8):18661875
  213. Cadie`re GB, Van Sante N, Graves JE, Gawlicka AK, Rajan A (2009) Two-year results of a feasibility study on antireflux transoral incisionless fundoplication using EsophyX. Surg Endosc 23(5):957964
  214. Bonavina L, DeMeester T, Fockens P, Dunn D, Saino G, Bona D, Lipham J, Bemelman W, Ganz RA (2010) Laparoscopic sphincter augmentation device eliminates reflux symptoms and normalizes esophageal acid exposure: one- and 2-year results of a feasibility trial. Ann Surg 252(5):857862
  215. Ganz RA, Peters JH, Horgan S, Bemelmann WA, Dunst CM, Edmundowicz SA, Lipham JC, Luketich JD, Melvin WS, Oe-lschlager BK, Schlack-Haerer SC, Smith CD, Smith CC, Dunn D, Taiganides PA (2013) Esophageal sphincter device for GERD. N Engl J Med 368(8):719727
  216. Pointner R, Bammer T, Then P, Kamolz T (1999) Laparoscopic refundoplications after failed antireflux surgery. Am J Surg 178(6):541544
  217. Donkervoort SC, Bais JE, Rijnhart-de Jong H, Gooszen HG (2003) Impact of anatomical wrap position on the outcome of Nissen fundoplication. Br J Surg 90:854859
  218. Draaisma WA, Rijnhartde Jong HG, Broeders IA, Smout AJ, Furnee EJ, Gooszen HG (2006) Five-year subjective and objective results of laparoscopic and conventional Nissen fundoplication: a randomized trial. Ann Surg 244:3441
  219. Furnée EJ, Draaisma WA, Broeders IA, Smout AJ, Vlek AL, Gooszen HG (2008) Predictors of symptomatic and objective outcomes after surgical reintervention for failed antireflux surgery. Br J Surg 95:13691374
  220. Furnée EJ, Draaisma WA, Broeders IA, Gooszen HG (2009) Surgical reintervention after failed antireflux surgery: a systematic review of the literature. J Gastrointest Surg 13:15391549
  221. Kessing BF, Bredenoord AJ, Smout AJ (2011) Erroneous diagnosis of gastroesophageal reflux disease in achalasia. Clin Gastroenterol Hepatol 9(12):10201024
  222. Luostarinen ME, Isolauri JO, Koskinen MO, Laitinen JO, Matikainen MJ, Lindholm TS (1993) Refundoplication for recurrent gastroesophageal reflux. World J Surg 17:587593
  223. Bonavina L, Chella B, Segalin A, Incarbone R, Peracchia A (1998) Surgical therapy in patients with failed antireflux repairs. Hepatogastroenterology 45:13441347
  224. Hunter JG, Smith CD, Branum GD, Waring JP, Trus TL, Cornwell M, Galloway K (1999) Laparoscopic fundoplication failures: patterns of failure and response to fundoplication revision. Ann Surg 230:595604
  225. Heniford BT, Matthews BD, Kercher KW, Pollinger H, Sing RF (2002) Surgical experience in fifty-five consecutive reoperative fundoplications. Am J Surg 68:949954
  226. Dutta S, Bamehriz F, Boghossian T, Pottruff CG, Anvari M (2004) Outcome of laparoscopic redo fundoplication. Surg En-dosc 18:440443
  227. Byrne JP, Smithers BM, Nathanson LK, Martin I, Ong HS, Gotley DC (2005) Symptomatic and functional outcome after laparoscopic reoperation for failed antireflux surgery. Br J Surg 92:9961001
  228. Wykypiel H, Kamolz T, Steiner P, Klingler A, Granderath FA, Pointner R, Wetscher GJ (2005) Austrian experience with redo antireflux surgery. Surg Endosc 19(11):14391446
  229. Furnee EJ, Draaisma WA, Broeders IA, Smout AJ, Gooszen HG (2008) Surgical reintervention after antireflux surgery for gas-troesophageal reflux disease: a prospective cohort study in 130 patients. Arch Surg 143:267274
  230. Weusten BL, Roelofs JM, Akkermans LM, Van Berge-Hene-gouwen GP, Smout AJ (1994) The symptom-association probability: an improved method for symptom analysis of 24-hour esophageal pH data. Gastroenterology 107:17411745
  231. Kessing BF, Smout AJ, Bredenoord AJ (2012) Clinical applications of esophageal impedance monitoring and high-resolution manometry. Curr Gastroenterol Rep 14:197205
  232. Yang H, Meun C, Sun X, Watson DI (2012) Outcome following management of dysphagia after laparoscopic anti-reflux surgery. World J Surg 36:838843
  233. Velanovich V, Vallance SR, Gusz JR, Tapia FV, Harkabus MA (1996) Quality of life scale for gastroesophageal reflux disease. J Am Coll Surg 183:217224
  234. Association American Gastroenterological, Spechler SJ, Sharma P, Souza RF, Inadomi JM, Shaheen NJ (2011) American Gastroenterological Association medical position statement on the management of Barretts esophagus. Gastroenterology 140:10841091
  235. Playford RJ (2006) New British Society of Gastroenterology (BSG) guidelines for the diagnosis and management of Barretts oesophagus. Gut 3:442443
  236. Reid BJ, Haggitt RC, Rubin LE, Rabinovictch PS (1987) Barretts esophagus: correlation between flow cytometry and histology in detection of patients at risk for adenocarcinoma. Gastroenterology 93:111
  237. Hvid-Jensen F, Pedersen L, Drewes AM, Sorensen HT, Fuch-Jensen P (2011) Incidence of adenocarcinoma in patients with Barretts esophagus. New Engl J Med 365(15):13751383
  238. Rugge M, Zaninotto G, Parente P, Zanatta L et al (2012) Barretts esophagus and risk of adenocarcinoma: the experience of the North-East Italian registry (EBRA). Ann Surg 256:788794
  239. Horwhath JD, Baroni D, Maydonowitch C, Osgard E, Orsmeth E et al (2006) Normalization of intestinal metaplasia in the esophagus and esophagogastric junction: incidence and clinical data. Am J Gastroenterol 101:110
  240. Spechler SJ, Sharma P, Traxler B, Levine D, Falk GW (2006) Gastric and esophageal pH in patients with Barretts esophagus treated with three omeprazole dosages: a randomized double-blind crossover trial. Am J Gastroenterol 101:19641971
  241. Parrilla P, de Martınez Haro ML, Ortiz A, Munitiz V et al (2003) Long-term results of a randomized prospective study comparing medical and surgical treatment of Barretts esophagus. Ann Surg 237:2
  242. Farrell TM, Smith CD, Metreveli RE, Johnson AB et al (1999) Fundoplication provides effective and durable symptom relief in patients with Barretts esophagus. Am J Surg 178:1821
  243. Gurski RA, Peters JH, Hagen JA, DeMeester SD (2003) Barretts esophagus can and does regress after antireflux surgery: a study of prevalence and predictive features. J Am Coll Surg 196:706713
  244. Abbas EA, Deschamps C, Cassivi SD, Allen MS et al (2004) Barretts esophagus: the role of fundoplication. Ann Thorac Surg 77:393396
  245. Biertho L, Dallemagne B, Dewandre JM, Jehaes C et al (2007) Laparoscopic treatment of Barretts esophagus. Long-term results. Surg Endosc 21:1115
  246. Cowgill SM, Al-Saadi S, Villadolid D, Zervos EE, Rosemurgy AS (2006) Does Barretts esophagus impact outcome after lap-aroscopic Nissen fundoplication? Am J Surg 192:622626
  247. Attwood SE, Lundell L, Hatlebakk JG, Eklund S, Junghard O et al (2008) Medical or surgical management of GERD patients with Barretts esophagus: the LOTUS trial three-year experience. J Gastrointest Surg 12:16461655
  248. Caygill CP, Watson A, Lao-Siriex P, Fitzgerald RC (2004) Barretts oesophagus and adenocarcinoma. World J Surg Oncol 2:12
  249. Avidan B, Sonnenberg A, Schnell TG, Chejfeg G, Metz A, Sontag SJ (2002) Hiatal hernia size, Barretts length and severity of reflux are all risk factors for esophageal adenocarcinoma. Am J Gastroenterol 97:19301936
  250. Oelschlager BK, Barreca M, Chang L, Oleynikov D, Pellegrini CA (2003) Clinical and pathologic response of Barretts esophagus to laparoscopic antireflux surgery. Ann Surg 238:458466
  251. Zaninotto G, Parente P, Salvador R, Farinati F, Tieppo C et al (2012) Long-term follow-up of Barretts epithelium: medical versus antireflux surgical therapy. J Gastrointest Surg 16:715
  252. Csendes A, Braghetto I, Burdiles P, Smok G et al (2006) Regression of intestinal metaplasia to cardiac or fundic mucosa in patients with Barretts esophagus submitted to vagotomy, partial gastrectomy and duodenal diversion. A prospective study of 78 patients with more than 5 years of follow-up. Surgery 139:4653
  253. Zaninotto G, Cassaro M, Pennelli G, Battaglia G, Farinati F et al (2005) Barretts epithelium after antireflux surgery. J Gastroin-test Surg 9:12531261
  254. Chang EY, Morris CD, Seltman AK, ORourke RW et al (2007) The effect of antireflux surgery on esophageal carcinogenesis in patients with Barrett esophagus: a systematic review. Ann Surg 246:1121
  255. Corey KE, Schmitz SM, Shaheen NJ (2003) Does a surgical antireflux procedure decrease the incidence of esophageal ade-nocarcinoma in Barretts esophagus? A meta-analysis. Am J Gastroenterol 98:23902394
  256. Csendes A, Burdiles P, Braghetto I, Korn O (2004) Adenocarcinoma appearing very late after antireflux surgery for Barretts esophagus: long-term follow-up, review of the literature, and addition of six patients. J Gastrointest Surg 8:434441
  257. Ortiz A, Martinez de Haro LF, Parrilla P et al (1999) Conservative treatment versus antireflux surgery in Barretts oesophagus: long-term results of a prospective study. Br J Surg 83:274278
  258. McDonald ML, Trastek VF, Allen MS et al (1996) Barretts esophagus: does an antireflux procedure reduce the need for endo-scopic surveillance? J Thorac Cardiovasc Surg 111:11351138
  259. Lofdahl HE, Lu Y, Lagergren P, Lagergren J (2013) Risk factors for esophageal adenocarcinoma after antireflux surgery. Ann Surg 257:579582
  260. Nelson SP, Chen EH, Syniar GM (1997) Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group. Arch Pediatr Adolesc Med 151:569572
  261. Martin AJ, Pratt N, Kennedy JD (2002) Natural history and familial relationships of infant spilling to 9 years of age. Pediatrics 109:10611067
  262. Stanford EA, Chambers CT, Craig KD (2006) The role of developmental factors in predicting young childrens use of a self-report scale for pain. Pain 120:1623
  263. von Baeyer CL, Spagrud LJ (2007) Systematic review of observational (behavioral) measures of pain for children and adolescents aged 318 years. Pain 127:140150
  264. Vandenplas Y, Rudolph CD, Di Lorenzo C, Hassall E, Liptak G, Mazur L, Sondheimer J, Staiano A, Thomson M, Veereman-Wauters G, Wenzl TG, North American Society for Pediatric Gastroenterology Hepatology and Nutrition, European Society for Pediatric Gastroenterology Hepatology and Nutrition (2009) Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NAS-PHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr 49:498547
  265. Gupta SK, Hassall E, Chiu Y-L, Amer F, Heyman MB (2006) Presenting symptoms of nonerosive and erosive esophagitis in pediatric patients. Dig Dis Sci 51:858863
  266. Kinsbourne M (1964) Hiatus hernia with contortions of the neck. Lancet 13:10581061
  267. Cerimagic D, Ivkic G, Bilic E (2008) Neuroanatomical basis of Sandifers syndrome: a new vagal reflex? Med Hypotheses 70:957961
  268. Rasquin A, Di Lorenzo C, Forbes D (2006) Childhood functional gastrointestinal disorders: child/adolescent. Gastroenter-ology 130:15271537
  269. Sullivan PB (1997) Gastrointestinal problems in the neurologically impaired child. Baillieres Clin Gastroenterol 11(3):529546
  270. Vandenplas Y, Hassall E (2002) Mechanisms of gastroesopha-geal reflux and gastroesophageal reflux disease. J Paediatr Gastroenterol Nutr 35:119136
  271. Kawahara H, Dent J, Davidson G (1997) Mechanisms responsible for gastroesophageal reflux in children. Gastroenterology 113:399408
  272. Orenstein SR (1994) Gastroesophageal reflux. In: Hyman PE (ed) Pediatric gastrointestinal motility disorders. Academy Professional Information Services, New York, pp 5588
  273. Furuta GT, Liacouras CA, Collins MH et al (2007) Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 133:13421363
  274. Heine RG, Nethercote M, Rosenbaum J, Allen KJ (2011) Emerging management concepts for eosinophilic esophagitis in children. J Gastroenterol Hepatol 26(7):11061113
  275. Bohmer CJ, Klinkenberg-Knol EC, Niezen-de Boer MC et al (2000) Gastroesophageal reflux disease in intellectually disabled individuals: how often, how serious, how manageable? Am J Gastroenterol 95:18681872
  276. Koivusalo A, Pakarinen MP, Rintala RJ (2007) The cumulative incidence of significant gastrooesophageal reflux in patients with oesophageal atresia with a distal fistulaa systematic clinical, pH-metric, and endoscopic follow-up study.
  277. J Pediatr Surg 42:370374 significant problem in patients with cystic fibrosis before and after lung transplantation. J Heart Lung Transplant 24:15221529
  278. Orenstein SR, Shalaby TM, Cohn JF (1996) Reflux symptoms in 100 normal infants: diagnostic validity of the infant gastro-esophageal reflux questionnaire. Clin Pediatr 35:607614
  279. Deal L, Gremse DA, Gremse DA, Winter HS, Peters SB, Fraga PD, Mack ME, Gaylord SM, Tolia V, Fitzgerald JF (2005) Age-specific questionnaires distinguish GERD symptom frequency and severity in infants and young children: development and initial validation. J Pediatr Gastroenterol Nutr 41(2):178185
  280. Vandenplas Y, Goyvaerts H, Helven R (1991) Gastroesophageal reflux, as measured by 24-hour pH monitoring, in 509 healthy infants screened for risk of sudden infant death syndrome. Pediatrics 88(4):834840
  281. Loots CM, Benninga MA, Davidson GP, Omari TI (2009) Addition of pH-impedance monitoring to standard pH monitoring increases the yield of symptom association analysis in infants and children with gastroesophageal reflux. J Pediatr 154(2):248252
  282. Thompson JK, Koehler RE, Richter JE (1994) Detection of gastroesophageal reflux: value of barium studies compared with 24-hr pH monitoring. AJR Am J Roentgenol 162:621626
  283. Van Den Driessche M, Veereman-Wauters G (2003) Gastric emptying in infants and children. Acta Gastroenterol Belg 66(4):274282
  284. Sherman PM, Hassall E, Fagundes-Neto U et al (2009) A global, evidence-based consensus on the definition of gastroesophageal reflux disease in the pediatric population. Am J Gastroenterol 104(5):12781295
  285. Vandenplas Y (1993) Hiatal hernia and gastro-oesophageal reflux. Elsevier Science, Management of Digestive and Liver Disorders in Infants and Children, Amsterdam, pp 103116
  286. Kumar Y, Sarvananthan R (2008) GORD in children. Clin Evid (Online) Pii:0310
  287. Mauritz FA, van Herwaarden-Lindeboom MYA, Stomp W et al (2011) The effects and efficacy of antireflux surgery in children with gastroesophageal reflux disease: a systematic review. J Gastrointest Surg 15:18721878
  288. Siddiqui MR, Abdulaal Y, Nisar A et al (2011) A meta-analysis of outcomes after open and laparoscopic Nissens fundoplication for gastro-oesophageal reflux disease in children. Pediatr Surg Int 27(4):359366
  289. Esposito C, Montupet P, van Der Zee D, Settimi A, Paye-Jaouen A, Centonze A et al (2006) Long-term outcome of laparoscopic Nissen, Toupet, and Thal antireflux procedures for neurologi-cally normal children with gastroesophageal reflux disease. Surg Endosc 20(6):855858
  290. Fonkalsrud EW, Ashcraft KW, Coran AG et al (1998) Surgical treatment of gastroesophageal reflux in children: a combined hospital study of 7467 patients. Pediatrics 101(3 Pt 1):419422
  291. Kubiak R, Andrews J, Grant HW (2011) Long-term outcome of laparoscopic Nissen fundoplication compared with laparoscopic thal fundoplication in children: a prospective, randomized study. Ann Surg 253(1):4449
  292. Mauritz FA, Blomberg BA, van Herwaarden-Lindeboom MYA et al (2013) Complete versus partial fundoplication in children with gastroesophageal reflux disease: results of a systematic review and meta-analysis. J Gastrointest Surg 17(10):18831892
  293. Stein HJ, Kauer WK, Feussner H, Siewert JR (1999) Bile acids as components of duodenogastric refluate: detection, relationship to bilirubin, mechanism of injury, and clinical relevance. Hepatogastroenterology 46:6673
  294. Bektas H, Schrem H, Lehner F, Schmidt U, Kreczik H, Kle-mpenauer J, Becker T (2006) The value of reoperative procedures after unusual reconstructions in the gastrointestinal tract associated with substantial morbidity. J Gastrointest Surg 10:111122
  295. Fuchs KH, Thiede A, Engemann R, Deltz E, Stremme O, Hamelmann H (1995) Reconstruction of the food passage after total gastrectomy: randomized trial. World J Surg 19:698705
  296. De Corso E, Baroni S, Agostino S, Cammarota G, Mascagna G, Mannocci A, Rignate M, Galli J (2007) Bile acids and total bilirubin detection in saliva of patients submitted to gastric surgery and in particular to subtotal Billroth II resection. Ann Surg 245:880885
  297. Chan DC, Fan YM, Lin CK, Chen CJ, Chen CY, Chao YC (2007) Roux-en-Y reconstruction after distal gastrectomy to reduce enterogastric reflux and Helicobacter pylori infection. J Gastrointest Surg 11:17321740
  298. Fein M, Fuchs KH, Thalheimer A, Freys S, Heimbucher J, Thiede A (2008) Long-term benefits of Roux-en-Y pouch reconstruction after total gastrectomy: a randomized trial. Ann Surg 247:759765
  299. Awais O, Luketich JD, Tam J, Irshad K, Schuchert MJ, Landreneau RJ, Pennathur A (2008) Rouy-en-Y near esophago-jejunostomy for intractable gastroesophageal reflux after anti-reflux surgery. Ann Thorac Surg 85:19541961

For the European Association of Endoscopic Surgery.

K. H. Fuchs (H), B. Babic, W. Breithaupt Department of Surgery, AGAPLESION Markus Krankenhaus, Wilhelm-Epstein-Str. 4, 60431 Frankfurt, Germany e-mail: krl-hermann.fuchs@fdk,inf

B. Dallemagne

IRCAD Institute, Strasbourg, France

A. Fingerhut Poissy, France

E.  Furnee

University Medical Center Utrecht, Utrecht, The Netherlands

F.  Granderath

Department of Surgery, Krankenhaus Neuwerk, Monchengladbach, Germany

P. Horvath

Department of Surgery, University of Pecs, Pecs, Hungary

P. Kardos

Group Practice & Respiratory Unit, Maingau Krankenhaus,

Frankfurt, Germany

R. Pointner

Department of Surgery, Krankenhaus Zell am See, Zell am See, Austria

E. Savarino

Department of Gastroenterology, University of Padua, Padua,


M. Van Herwaarden-Lindeboom

Department of Pediatric Surgery, University of Utrecht, Utrecht,

The Netherlands

G. Zaninotto

Department of Surgery, Imperial College, London, UK


. : " ", " -",
" ", " " .