Preoperative Diagnostic Workup before AntirefluxSurgery: AnEvidenceandExperience-BasedConsensusof the Esophageal Diagnostic Advisory Panel

Blair A Jobe, MD, FACS, Joel E Richter, MD, Toshitaka Hoppo, MD, PhD, Jeffrey H Peters, MD, FACS,Reginald Bell, MD, FACS, William C Dengler, MD, FACS, Kenneth DeVault, MD, Ronnie Fass, MD,C Prakash Gyawali, MD, Peter J Kahrilas, MD, Brian E Lacy, MD, PhD, FACG, John E Pandolfino, MD,Marco G Patti, MD, FACS, Lee L Swanstrom, MD, FACS, Ashwin A Kurian, MD, Marcelo F Vela, MD,Michael Vaezi, MD, Tom R DeMeester, MD, FACS

BACKGROUND: Gastroesophageal reflux disease (GERD) is a very prevalent disorder. Medical therapyimproves symptoms in some but not all patients. Antireflux surgery is an excellent optionfor patients with persistent symptoms such as regurgitation, as well as for those with completesymptomatic resolution on acid-suppressive therapy. However, proper patient selection iscritical to achieve excellent outcomes.

STUDY DESIGN: A panel of experts was assembled to review data and personal experience with regard to appro-priate preoperative evaluation for antireflux surgery and to construct an evidence andexperience-based consensus that has practical application.

RESULTS: The presence of reflux symptoms alone is not sufficient to support a diagnosis of GERDbefore antireflux surgery. Esophageal objective testing is required to physiologically andanatomically evaluate the presence and severity of GERD in all patients being consideredfor surgical intervention. It is critical to document the presence of abnormal distal esophagealacid exposure, especially when antireflux surgery is considered, and reflux-related symptomsshould be severe enough to outweigh the potential side effects of fundoplication. Each testingmodality has a specific role in the diagnosis and workup of GERD, and no single test alonecan provide the entire clinical picture. Results of testing are combined to document thepresence and extent of the disease and assist in planning the operative approach.

CONCLUSIONS: Currently, upper endoscopy, barium esophagram, pH testing, and manometry are requiredfor preoperative workup for antireflux surgery. Additional studies with long-term follow-up are required to evaluate the diagnostic and therapeutic benefit of new technologies, such asoropharyngeal pH testing, multichannel intraluminal impedance, and hypopharyngealmultichannel intraluminal impedance, in the context of patient selection for antirefluxsurgery. (J Am Coll Surg 2013;217:586e597. � 2013 by the American College of Surgeons)

Disclosure Information:Given Imaging, Inc. provided funding for honorariaand logistical support and sponsored the meeting of the Esophageal Diag-nostic Advisory Panel. Members of Given Imaging, Inc. were present forthe meeting but they were not involved in constructing the consensus state-ment or preparing the manuscript. The authors have no other disclosures.

Presented at the Esophageal Diagnostic Advisory Panel, Digestive DiseaseWeek 2012, San Diego, CA, May 2012.

Received March 12, 2013; Revised May 1, 2013; Accepted May 28, 2013.From the Department of Surgery, The Western Pennsylvania Hospital,West Penn Allegheny Health System, Pittsburgh, PA (Jobe, Hoppo), JoyMcCann Culverhouse Center for Swallowing Disorders, Division of Diges-tive Diseases and Nutrition, University of South Florida, Tampa, FL(Richter), Department of Surgery, University of Rochester Medical Center,Rochester, NY (Peters), SurgOne, PC, Englewood, CO (Bell), LegatoMedical Systems, Inc., Rocky Mount, NC (Dengler), Division of Gastroen-terology and Hepatology, Mayo Clinic in Florida, Jacksonville, FL

(DeVault), Division of Gastroenterology, MetroHealth Medical Center,Cleveland, OH (Fass), Division of Gastroenterology, Washington Univer-sity School of Medicine, St Louis, MO (Gyawali), Division of Gastroenter-ology, Northwestern Memorial Hospital (Kahrilas, Pandolfino), Center forEsophageal Diseases, The University of Chicago Medicine (Patti), Chicago,IL, Section of Gastroenterology and Hepatology, Dartmouth-HitchcockMedical Center, Lebanon, NH (Lacy), Minimally Invasive SurgeryDivision, The Oregon Clinic, Portland, OR (Swanstrom, Kurian), Sectionof Gastroenterology, Baylor College of Medicine and Michael E DeBakeyVA Medical Center, Houston, TX (Vela), Division of Gastroenterology,Vanderbilt University Medical Center, Nashville, TN (Vaezi), andDepartment of Surgery, Keck School of Medicine of University of SouthernCalifornia, Los Angeles, CA (DeMeester).Correspondence address: Blair A Jobe, MD, FACS, Department of Surgery,The Western Pennsylvania Hospital, North Tower, 4800 Friendship, Suite4600, Pittsburgh, PA 15224. email: bjobe1@wpahs.org

586ª 2013 by the American College of Surgeons ISSN 1072-7515/13/$36.00

Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jamcollsurg.2013.05.023

Abbreviations and Acronyms

BE ¼ Barrett esophagusGERD ¼ gastroesophageal reflux diseaseHMII ¼ hypopharyngeal multichannel intraluminal

impedanceLA ¼ Los AngelesLES ¼ lower esophageal sphincterLPR ¼ laryngopharyngeal refluxMII ¼ multichannel intraluminal impedancePPI ¼ proton pump inhibitorSAP ¼ symptom association probabilitySI ¼ symptom index

Vol. 217, No. 4, October 2013 Jobe et al Preoperative Workup for Antireflux Surgery 587

Gastroesophageal reflux disease (GERD) is the mostcommon esophageal disorder in Western countries.Epidemiologic studies have demonstrated that as manyas 7% of Americans have episodes of heartburn everyday, and approximately 42% experience heartburn at leastonce a month.1,2 Symptoms of gastroesophageal refluxnegatively affect patient quality of life. Research studieshave established that some patients with GERD havea worse quality of life than those with angina or conges-tive heart failure.3 Gastroesophageal reflux disease is asso-ciated with the retrograde flow of gastric and duodenalcontents into the esophagus, and potentially reachingproximal organs, such as the larynx and airway, causinga wide variety of symptoms with or without tissuedamage.4,5 Gastroesophageal reflux disease causes typicalsymptoms, such as heartburn (a retrosternal burningsensation), regurgitation, and dysphagia, and atypicalsymptoms, such as cough, hoarseness, globus sensation,and throat clearing. Additionally, GERD can contributeto development of pulmonary diseases, such as adult-onset asthma6 and idiopathic pulmonary fibrosis.7 It isimportant to keep in mind that these extraesophagealpresentations can have multifactorial, often non-GERD,causes, and causality between reflux and these clinicalentities is difficult to prove.The primary treatment options for GERD include

medical therapy (eg, proton pump inhibitors [PPIs]and/or H2 receptor antagonists) and laparoscopic surgicalreconstruction (fundoplication). Most patients withGERD are initially treated with acid-suppressive therapyusing PPIs and/or H2 receptor antagonists. A recentsystematic review demonstrated that despite adequateacid suppression, 32% of patients in randomized studiesand 45% in observational studies were found to havepersistent symptoms.8 Although antisecretory medica-tions reduce or eliminate the symptom of heartburn byincreasing the pH of gastric secretions, this therapy doesnot address the anatomically defective antireflux barrier

and episodes of weakly acidic esophageal exposure thatcontinue unabated in some patients. That said, not allpatients who fail to respond to medical therapy haveGERD and, in some, the ongoing symptoms are due tonon-GERD causes or even a functional gastrointestinaldisorder. With this in mind, it is very important to studythese patients adequately to distinguish those withongoing symptoms due to GERD vs non-GERD causes.When performed by an experienced surgeon, laparoscopicfundoplication is highly effective in patients with typicalGERD symptoms (eg, heartburn and regurgitation) anddocumented abnormal esophageal acid exposure.However, the long-term outcomes of antireflux surgeryhave varied depending on the center, from a 61% patientsatisfaction rate in a US community setting9 to up to94% in experienced centers (>10 years postoperativefollow-up).10,11

Although GERD is a common entity, the diagnosis ofGERD is not easy or straightforward for a number ofreasons. First, symptoms are nonspecific.12 Second, clin-ical presentation is heterogeneous, depending in part onan individual’s perception of their symptoms. Third,there is considerable overlap with other upper gastrointes-tinal disorders, such as functional dyspepsia and gastropa-resis.13,14 In fact, up to 30% of patients who present witha primary report of GERD symptoms do not haveabnormal distal esophageal acid exposure and wouldnot benefit from fundoplication.15,16 Therefore, objectiveesophageal testing is critical to document the presence ofGERD, especially when surgical treatment is considered.The goal of preoperative esophageal testing is to establishthe presence of abnormal distal and proximal esophagealacid exposure and correlate reflux events with symptoms.The testing can include upper endoscopy, barium esopha-gram, pH testing, esophageal manometry (high-resolu-tion manometry if available), multichannel intraluminalimpedance (MII) pH, and, in selective cases, a radiola-beled gastric emptying study. Each testing modality hasa specific role in the evaluation of GERD and resultsare combined to “paint the picture” of disease and assistin planning the operative approach. The Society ofAmerican Gastrointestinal and Endoscopic Surgeons rec-ommended that the diagnosis of GERD can be acceptedif at least one of the following conditions exists: mucosalbreak seen on endoscopy in a patient with typical symp-toms, Barrett esophagus (BE) confirmed on histology,peptic stricture in the absence of malignancy, or positivepH testing. These recommendations were based ona review of existing literature.17 In the era of PPIs, theseverity of mucosal injury encountered in the workupof GERD has been reduced, and new technologies havebeen introduced in an attempt to improve the sensitivity

588 Jobe et al Preoperative Workup for Antireflux Surgery J Am Coll Surg

of GERD diagnosis in patients being considered for anti-reflux surgery. The purpose of this consensus conferenceand the subsequent article was to define the optimalpreoperative diagnostic evaluation before primary antire-flux surgery and to construct an evidence and experience-based consensus with practical application. The workupand management of reoperative antireflux surgery wasnot discussed as part of this consensus.

ESOPHAGEAL DIAGNOSTIC ADVISORY PANELExperts who manage GERD, including gastroenterolo-gists and surgeons, in both academic and communitypractices were assembled as the Esophageal DiagnosticAdvisory Panel to achieve a practical consensus on theoptimal preoperative diagnostic evaluation before antire-flux surgery at Digestive Disease Week 2012 in SanDiego, CA on May 19, 2012. Given Imaging, whoprovided funding for honoraria and logistical support toorganize the meeting, sponsored the Esophageal Diag-nostic Advisory Panel. Members of Given Imaging werepresent for the meeting, however, they were not involvedin constructing the consensus statement or preparing thearticle. Drs Richter and Jobe framed the topics and ques-tions addressed by the panel.To provide consensus for practice in the United States

with attention to Food and Drug Administration labelingissues and insurance considerations, the members of theEsophageal Diagnostic Advisory Panel were selectedfrom the United States based on criteria developed bythe 2 chairs of the meeting (Drs Jobe and Richter) toenhance the discussion and assemble the clinical experi-ence of each member to construct an evidence andexperience-based consensus. Chairs led a free discussionon each question and at the end of each discussion aninformal vote was held to determine a consensus. Themeeting was recorded and the chairs reviewed the tran-script. A draft was generated and distributed to eachmember for review and edits. Once all issues wereaddressed, a final document with consensus was generatedand sent back to the members for final approval.

Is a symptom-based diagnosis of gastroesophagealreflux disease sufficient for antireflux surgery?

Preoperative evaluation starts with meticulous historytaking, including clinical symptoms (typical vs atypical);use of antisecretory medication; existing comorbidities;and additional symptoms, such as bloating, nausea, vom-iting, and diarrhea, all of which can affect the outcomesof antireflux surgery (Table 1). The first panel discussioncentered on the question: are symptoms alone (typicaland atypical) or with PPI response sufficient to support

a diagnosis of GERD before antireflux surgery? It wasnoted that the clinical presentation of GERD is heteroge-neous and dependent on an individuals’ perception, withor without PPI response. In the DIAMOND study, thesensitivity and specificity for the symptom-based diag-nosis of GERD in patients with heartburn and/or regur-gitation is 49% and 74%, respectively, and symptomaticresponse to a 2-week course of PPI did not improve thediagnostic yield.19,20 In addition, previous work hasdemonstrated that PPI therapy is associated with a consid-erable placebo effect, especially in patients with extraeso-phageal symptoms.21,22 It is noted that the symptoms ofboth functional dyspepsia14 and irritable bowelsyndrome23 can overlap with those of GERD, anda GERD-specific questionnaire might not adequatelydistinguish these 3 entities. Based on these considerations,the consensus of the Esophageal Diagnostic AdvisoryPanel was that symptoms by themselves or their respon-siveness to PPIs are not sufficient criteria to supporta diagnosis of GERD before antireflux surgery.This statement is supported by the recent recommen-

dations issued by the Esophageal Diagnostic WorkingGroup,24 stating that symptom type or severity isa poor predictor of baseline GERD status, especially forextraesophageal symptoms, thereby highlighting thenecessity to document objective findings of GERD inpatients not responding to PPI therapy in whom an anti-reflux procedure is being contemplated. Although notformally addressed by the panel, some believed that theoutcomes of an antireflux procedure should be assessedbased not only on patient-reported symptomaticimprovement, but also with anatomic (eg, resolution ofesophagitis) and physiologic (eg, normalization of distalesophageal acid exposure using pH monitoring) bench-marks.25 Table 2 highlights the currently available testingmodalities, the rationales for performing the tests, theresult that would best support the decision to proceedwith antireflux surgery, and potential pitfalls associatedwith each test.

Testing for esophageal structural abnormalities

Upper endoscopy

Esophageal mucosal injury, such as esophagitis or BE, isa very specific but not sensitive indicator for the presenceof GERD. Mucosal injury occurs secondary to predispos-ing factors, including a mechanically defective loweresophageal sphincter (LES), poor esophageal motility,hiatal hernia, and a subsequent increase in esophagealexposure to gastric refluxate with a pH <4.26 To objec-tively describe the severity of esophagitis, the Los Angeles(LA) Classification was introduced into practice27;however, LA grades A and B esophagitis can be

Table 1. Approach to the Patient Being Evaluated forAntireflux Surgery

Goals in preoperative evaluation prior to ARSDefine symptoms potentially attributable to GERDUnderstand comorbid conditions as they relate to surgical riskObjectify GERD with physiology testingIdentify esophageal anatomic abnormalitiesIdentify esophageal functional abnormalitiesSet expectations with patientPlan surgical approach

History and expectation settingQuery typical versus atypical symptomsExclude non-GERD causes of typical and atypical symptomsUnderstand primary and secondary symptoms (“if you couldonly pick one to eliminate”)

Gauge the degree of response to and dependence uponantisecretory therapy

Query for non-GERD associated symptoms such as bloating,emesis, nausea, vomiting, diarrhea

Ask about eating disorderCounsel patient as to the probability of success

(Reprinted from Watson and Peters,18 with permission.)ARS, antireflux surgery; GERD, gastroesophageal reflux disease.

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diagnostically nonspecific,16 and there can be unaccept-able inter-observer variability.28 Based on this observationand much debate within the consensus panel, we reachedthe ultimate decision that patients with endoscopic find-ings of LA grade A or mild B esophagitis require pHtesting to document the presence of GERD, and thosewith LA grade C or D do not need it, providing thatpill esophagitis and achalasia have been excluded. It wasnoted that in the era of PPI therapy, endoscopic findingsof esophagitis are much less common, and the absence ofesophagitis in no way excludes a diagnosis of GERD.Ambulatory pH testing can be used with any classificationof esophagitis if there is ambiguity related to the diagnosisor if the clinician wishes to gauge the severity of reflux asa baseline before surgery.Nonerosive reflux disease is thought to be a distinct

phenotype of GERD that can be subcategorized intothe following types based on the results of pH testing:patients with an abnormal pH test but no mucosal injury;patients with a normal pH test but with symptoms andreflux events that temporally correlate, suggesting acidhypersensitivity; and patients with a normal pH testand no symptom correlation with reflux events.29 Patientswith an abnormal pH test but no mucosal injuryare commonly encountered, and these patients requireadditional testing to document the presence of patholog-ical GERD. In these patients, it is particularly importantthat a meticulous surgical history and/or history of othergastrointestinal symptoms (eg, irritable bowel syndrome)be obtained to carefully consider whether the correctionof abnormal acid exposure by antireflux surgery will

worsen the existing non-GERD gastrointestinal symp-toms. A patient with pH-negative nonerosive refluxdisease might not be adequately treated with antirefluxsurgery, and it is important to identify these patientswith objective testing. The Esophageal Diagnostic Advi-sory Panel did not formally discuss these subcategoriesof nonerosive reflux disease and, in post-hoc discussions,agreed that there might be insufficient data to supportclinical decision making based on this taxonomy;however, all participants agreed that the use of antirefluxsurgery in patients with a negative pH test should beavoided. In patients with suspected GERD and a negativepH test, it is critically important to eliminate any errors inpH testing, such as a misplaced pH probe, and tomeasure the esophageal acid exposure using thecomposite pH score.12 Because the differential betweennormal and abnormal acid exposure in early-stage diseaseis extremely small, errors in pH testing are more likely tooccur; the composite pH score might provide a moredetailed evaluation of the patterns of acid exposure inthese patients so that subtle differences are not over-looked. A pH probe should be carefully positioned basedon the manometric measurement of the upper border ofthe LES and a measured delivery catheter containing thepH capsule inserted through the nose. Alternatively,a measured nasogastric tube can be placed through thenose to target the site of attachment and the delivery cath-eter containing the pH capsule inserted through themouth and attached under endoscopic control.Barrett esophagus represents an advanced form of

GERD defined as a columnar-lined segment of esophagusvisible on endoscopy in conjunction with pathologic find-ings of intestinal metaplasia with the presence of gobletcells. There is a distinction between short-segment BE(<3 cm) and long-segment BE (�3 cm), and the vali-dated Prague classification has been used to objectivelydescribe the endoscopic appearance of BE. However,this classification system can be associated with inter-observer variability, especially involving short-segmentlesions with <1-cm length of BE.30 In addition, this studydemonstrated that approximately 50% of patients whohad endoscopic findings of short-segment BE wereconfirmed histologically.31 Based on these findings, webelieved that short-segment BE still requires additionaldocumentation to validate the presence of GERD,although histologically confirmed short-segment BE isdiagnostic of GERD. The consensus was that patientswith long-segment BE (�3 cm) do not require pHtesting; however, those with short-segment BE (<3 cm),including intestinal metaplasia of the cardia, requirepH testing to document the presence of GERD beforeantireflux surgery.

Table 2. Overview of Esophageal Testing Modalities to Be Considered in Patients Being Evaluated for Antireflux Surgery

Testing modalityRequired in every patient

considered for ARS Principal reasons the test is performed

Result that supports GERDdiagnosis and might suggest

success with ARS Potential pitfall

Symptom stratification Yes Symptom type is predictor of surgicaloutcomes

HB, regurgitation Symptoms unrelated to GERD

PPI test No Response supports diagnosis and is apredictor of surgical outcomes

PPI dependence to controlprimary symptom

Intolerance of PPI; placebo effect;symptomatic nonacid reflux

Barium esophagram Yes Evaluate global anatomy for structuralproblem

Hiatal hernia (any size) andreflux to level of clavicles

Normal examination; poor-qualityexamination

Upper endoscopy Yes Evaluate mucosa for BE and esophagitis Esophagitis Normal examination

Esophageal manometry Yes Rule out achalasia and plan surgicalapproach

Defective LES, intact effectiveperistalsis

Error in interpretation

Off-PPI pH testing Yes (unless LA C, LA D, orlong-segment BE on endoscopy)

Document pathologic acid reflux andcorrelate reflux events with symptoms,especially in patients with nonerosiveGERD

Positive pH test and/or positivesymptom correlation for HB,chest pain, or regurgitation

Atrophic gastritis; lactic acidproduction in achalasia; wrongposition of pH probe; positivetest in patients with eatingdisorder

Gastric emptying study No Evaluate for delayed gastric emptying inpatients with bloating and/or nausea inthe face of a normal LES pressure andlength

Normal gastric emptying study Gastric outlet obstruction“masquerading” as delayedgastric emptying

HMII-pH and MII-pH No (the addition of impedanceto standard pH testing mightbe advantageous, especially inpatients on PPI or those withlaryngeal symptoms)

Understand the contribution of symptomaticnonacid reflux in the face of PPI therapy

Symptom correlation withnonacid reflux eventscombined with a positivepH test

HMII distal pH probe misplacedleading to inaccurate pH test

ARS, antireflux surgery; BE, Barrett esophagus; HB, heartburn; HMII, hypopharyngeal multichannel intraluminal impedance; LA, Los Angeles; LES, lower esophageal sphincter; LPR,laryngopharyngeal reflux; PPI, proton pump inhibitor; MII, multichannel intraluminal impedance.

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Barium esophagram

Barium esophagram provides anatomic and functionalinformation on esophageal length, presence and size ofhiatal hernia, diverticulum, esophageal stricture, as wellas the presence of gastroesophageal reflux eventswith provocation. The esophagram is ideally a video-recorded examination to evaluate the dynamic changesof the esophagus in terms of esophageal peristalsis, bolustransport, and reducibility of hiatal hernia. One poten-tial objective of the preoperative esophagram is to differ-entiate between a type III paraesophageal (mixed) herniaand type I sliding hernia, as upper endoscopy can beinaccurate in this context.32 The consensus of the Esoph-ageal Diagnostic Advisory Panel was that all patientswho are considered for antireflux surgery require bariumesophagram. A type III paraesophageal (mixed) hernia isassociated with progression of symptoms (heartburn,dysphagia, chest pain, regurgitation) in up to 45% ofpatient without surgical intervention,33 and also signifi-cant, sometimes catastrophic, complications, such astorsion, gangrene, perforation, and massive hemor-rhage.34 Based on this, a paraesophageal hernia shouldbe electively repaired regardless of whether patientshave documented GERD; contrast esophagram, upperendoscopy, and manometry should be performed as forGERD because an antireflux procedure is most oftenperformed as an integral component of this procedure(pH is not required in these patients). It should be notedthat the optimal preoperative evaluation of paraesopha-geal hernia was not discussed as part of this consensuspanel.It is noted that barium esophagram is not dependable

in GERD patients with a large hiatal hernia or pepticstricture in the preoperative determination of shortesophagus that will require Collis gastroplasty. This issupported by previous studies demonstrating that preop-erative esophagram and manometry are not reliablepredictors of the short esophagus (sensitivity 66% and43%, respectively),35 and the endoscopic findings ofeither a stricture or BE are the most sensitive indicatorsthat a lengthening procedure might be necessary.35,36

This examination raises awareness of the possibility ofshort esophagus, thereby enabling more detailed preoper-ative counseling and planning. Because the quality ofa given esophagram is highly variable among radiologistsand institutions, a standardized protocol that highlightsthe important aspects of anatomy and function (presenceand type of hernia, reducibility of hernia in the uprightposition, signs of obstruction, presence and level ofgastroesophageal reflux, motility status, diverticulum,and provocative maneuvers) is suggested.

Testing for esophageal physiology abnormalities

Esophageal manometry

Esophageal manometry is the most reliable method toassess the function of the LES and the esophageal body.Patients with GERD might have manometric findings ofa defective LES (approximately 60%)26,37 or impairedesophageal motility that is associated with the severity ofesophagitis (25% of patients with mild esophagitis hadimpaired esophageal motility vs 48% of those with severeesophagitis).38 The primary purposes of performing esoph-ageal manometry before antireflux surgery are to excludeachalasia, which might be misdiagnosed as GERD; assessperistaltic coordination and contractile force of the esoph-ageal body based on which antireflux surgery can betailored (total vs partial fundoplication); and measure theprecise location of the gastroesophageal junction for accu-rate pH probe or impedance catheter placement. The clin-ical application of 32-channel high-resolution manometryhas made esophageal manometry easier, faster, and moreaccurate. High-resolution manometry provides real-timemonitoring of contractile activity over the entire esopha-geal length and, when coupled with impedance, measureseffectiveness of bolus clearance with each swallow.However, there have been no controlled data to supportthe therapeutic benefit of tailoring the degree of fundopli-cation based on preoperative esophageal motilitystatus.39,40 Based on these findings, the consensus of theEsophageal Diagnostic Advisory Panel was that esophagealmanometry should be performed in all patients beingconsidered for antireflux surgery to exclude achalasia,and esophageal manometry can be useful to guide thetype of antireflux surgery, as patients with frequent failedperistalsis and/or weak peristalsis with peristaltic defectsmight have less dysphagia with partial fundoplication.The Esophageal Diagnostic Advisory Panel did not discussthe type of partial fundoplication that should be used inthe context of peristaltic failure.

Esophageal pH testing with/without impedance

Ambulatory pH testing is the gold standard to determineif there is pathological GERD. This can be done viaa transnasal catheter for 24 hours or the wireless pHsystem, which collects 48 hours of pH data.41,42 It hasbeen reported that 48-hour pH testing can increase detec-tion accuracy and sensitivity for abnormal esophagealacid exposure by as much as 22%.43 Previous studiesdemonstrate that an abnormal 24-hour pH test ina PPI-dependent patient with typical symptoms predictssuccessful outcomes with antireflux surgery,44 and thosewith typical symptoms without an abnormal pH testare less likely to have successful outcomes.45 Recently,

Figure 1. The approach to patients with gastroesphogeal reflux disease symptoms notresponding to medical therapy, constructed by the Esophageal Diagnostic Working Group.

592 Jobe et al Preoperative Workup for Antireflux Surgery J Am Coll Surg

the Esophageal Diagnostic Working Group publishedtheir recommendations on the appropriate use of wirelesspH testing,24 stating that documentation of pathologicacid gastroesophageal reflux off acid suppression is animportant measurement in the management of GERDin patients not responding to PPI therapy and those beingconsidered for antireflux surgery (Fig. 1). Similarly, theconsensus of the Esophageal Diagnostic Advisory Panelwas that pH testing at least 7 days off acid suppressionshould be performed in all patients with nonerosiveGERD, those with LA Classification grade A or mildB esophagitis, and in patients with short-segment BE(<3 cm).Esophageal pH testing can be combined with MII-pH.

Because MII-PH can detect any type of reflux event (acid,pH <4; weak acid, pH 4 to 6; and nonacid, pH >6;nonacid) regardless of pH, it is a promising tool to eval-uate GERD, especially in patients who are refractory orunresponsive to PPI therapy.46,47 Three studies involvinghealthy subjects have established normative values forambulatory 24-hour MII-pH for a specific catheterconfiguration.48-50 Using these data as a reference point,subsequent studies have demonstrated that both thenumbers of reflux events and GERD symptomsimproved after antireflux surgery in patient groups withsymptomatic acid and nonacid reflux on PPI therapy.51,52

There are 3 studies (1 in abstract form) that have estab-lished the normative MII-pH values in patients on acid

suppression.53,54 However, a recent study involving 237patients with GERD did not show any benefit of24-hour MII-pH on acid suppression to predict theoutcomes of antireflux surgery; the implication of thisstudy is that the role of antireflux surgery in patientswith abnormal nonacid reflux on acid suppressionremains unclear.55 The consensus of the panel was thatthere is insufficient data to justify the decision to proceedwith antireflux surgery in patients with a positive MII-pH on acid suppression who are refractory to PPI therapyor in patients who had a negative pH test but anabnormal number of reflux events as measured by MII-pH. The Esophageal Diagnostic Advisory Panel recog-nized the need for additional studies to clarify the roleof MII-pH monitoring findings to select patients forantireflux surgery. They agreed that if a pH study wasperformed on acid suppression that resulted in a positivepH test, regardless of whether it is combined with imped-ance, that positive study could be used to select a patientfor antireflux surgery; however, the same abnormal valuesoff acid suppression should be used to determine if thereis pathologic GERD.

Symptom association and pH testing

It is important to determine if there is any correlationbetween patients’ symptoms and reflux events. Asymptom is usually considered to be associated witha reflux event if it occurs within a 2-minute interval after

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the reflux event. The Symptom Index (SI)56 and theSymptom Association Probability (SAP)57 are commonlyused to evaluate the temporal association between clinicalsymptoms and reflux events. The SI provides an assess-ment of the overall strength of the relationship, and anySI �50% is considered positive.58 The SAP determineswhether this relationship could have occurred by chance,and an SAP >95% is statistically significant.57 However,the SI and SAP, which are calculated by the analysis soft-ware without manual reading of the tracings, were vali-dated only for acid-related (not nonacid by MII-PH)heartburn, regurgitation, and chest pain, and are highlydependent on the numbers of symptoms provided bypatients during the testing period. Patients who havea positive SI and/or SAP in the evaluation of typicalsymptoms likely have GERD as the cause of their symp-toms; however, the primary issue of whether there ishypersensitivity to acid exposure or a component of func-tional heartburn is not addressed by this scoring system.Although there is some evidence to support the effective-ness of antireflux surgery in patients with esophagealhypersensitivity,59 this is a clinical scenario that requiresindividualization and careful preoperative counseling.The Esophageal Diagnostic Advisory Panel believed thatthe decision to proceed with antireflux surgery shouldnot be made based solely on a positive SI and/or SAP.It is noted that the reflux-related symptoms should besevere enough to outweigh the potential side effects ofantireflux surgery, and this should be reflected in long-term post-procedure quality of life improvement.60,61

Gastric emptying

Delayed gastric emptying causes bloating, abdominaldistension, and nausea; however, these symptoms arenot specific for gastroparesis, and functional dyspepsiahas the similar, nonspecific upper gastrointestinal symp-toms as gastroparesis. A 4-hour solid-phase gastricemptying study has been recommended62; however, itcannot distinguish patients with functional dyspepsiafrom those with nondiabetic gastroparesis, given that30% of patients with functional dyspepsia have delayedgastric emptying.63 Approximately 20% of patients withGERD have some degree of delayed gastric emptying byscintigraphic assessment. Fundoplication improvesgastric emptying in patients with GERD by reducingthe capacity of the fundus reservoir and/or the radius ofthe proximal stomach, generating a higher intraluminalpressure and promoting the passage of food bolus.64-66

However, persistent delayed gastric emptying can leadto unsatisfactory outcomes of antireflux surgery andworsen the gas-bloat symptoms that can occur afterthis operation. Currently, there are no established

preoperative gastric emptying study cut-off values thatpredict worsening of postoperative gas bloat, althoughdelayed gastric emptying is currently defined as tracerretention >90% at 1 hour, 60% at 2 hours, and 10%at 4 hours.67 A large prospective trial involving 372patients with GERD who had undergone fundoplication,demonstrated that 31% of patients were found to havedelayed gastric emptying preoperatively; however,there was no relationship between preoperative gastricemptying status and outcomes of fundoplication.68 Thegastric emptying study is not a routine part of the preop-erative workup before anti-reflux surgery. The consensusof Esophageal Diagnostic Advisory Panel was thata gastric emptying study should be obtained selectivelyin the preoperative evaluation of patients with signifi-cant nausea, vomiting, and bloating or those withretained food in the stomach after an overnight fast onendoscopy. The study should be performed for 4 hours,not 2 hours.

Objective testing for laryngopharyngeal reflux

Laryngopharyngeal reflux (LPR) has been recognized asa common entity, affecting approximately 20% of theAmerican population.69,70 However, these symptoms canalso be associated with coexisting causative factors otherthan GERD, such as tobacco/alcohol abuse, allergies,postnasal drip, and chronic sinusitis, which irritate thehypopharynx. A 3-month trial of empiric PPI therapyhas been recommended as an initial step in the diagnosisand treatment of LPR71; however, recent meta-analysesdemonstrated no therapeutic benefit of PPIs in thissetting.72,73 The outcomes of antireflux surgery when per-formed for LPR symptoms are less favorable comparedwith those achieved in patients with typical GERD symp-toms, because of the potentially multifactorial nature ofLPR symptoms (ie, non-GERD causes) and absence ofa testing modality with sufficient sensitivity to directlymeasure LPR events, establishing GERD as the under-lying cause. Recently, 2 promising tools includingoropharyngeal pH testing (Restech; Respiratory Tech-nology Corporation) and hypopharyngeal multichannelintraluminal impedance (HMII-pH) (Sandhill ScientificInc.) have been introduced and investigated.The oropharyngeal pH catheter is a device used to

measure oropharyngeal acid reflux and attempts to estab-lish the temporal relationship between extraesophagealreflux symptoms and LPR acid events. The device hasan ion flow sensor that enables accurate measurementof the pH in both liquid and aerosolized droplets in theoropharynx. Several studies to evaluate the diagnosticbenefit of oropharyngeal pH testing have been reportedin patients with LPR symptoms.74-76 However, there are

Table 3. Experience-Based Consensus Statements Developed by the Esophageal Diagnostic Advisory Panel

Testing approach Consensus statement based on provider experience

Symptom stratification and PPI test Symptoms with or without a PPI response are not sufficient to support a diagnosis of GERDwhen considering antireflux surgery.

Upper endoscopydesophagitis Endoscopic findings of Los Angeles grade A or mild B esophagitis require pH testing todocument the presence of GERD, and those with Los Angeles grade C or D do not, providedpill esophagitis and achalasia have been excluded.

Upper endoscopydBarrett esophagus Patients with long-segment BE (�3 cm) do not require pH testing; however, those with short-segment BE (<3 cm), including intestinal metaplasia of the cardia, require pH testing todocument the presence of GERD before antireflux surgery.

Barium esophagram Patients who are considered for antireflux surgery require esophagram.

Esophageal manometry Manometry should be performed in all patients being considered for antireflux surgery toexclude achalasia. Manometry can be useful to tailor antireflux surgery as patients withfrequent failed peristalsis and/or weak peristalsis with peristaltic defects can have less dysphagiawith partial fundoplication.

pH testing pH testing 7 days off acid suppression should be performed in all “nonerosive” GERD patientsand those with Los Angeles grade A or mild B esophagitis.

pH testing with or without MII A positive pH test on acid suppression, regardless of whether it is combined with impedance canbe used to select a patient for antireflux surgery. In this context, the same cut-offs as withtesting off acid suppression should be used to define pathologic GERD.

Symptom association scoring The decision to proceed with antireflux surgery should not be based solely on a positive SI and/orSAP. It is important that the reflux-related symptoms be severe enough to outweigh the sideeffects of antireflux surgery.

Gastric emptying A gastric emptying study should be obtained selectively in patients with significant nausea andbloating or those with retained food in the stomach after an overnight fast. When done, thetest should be performed for 4 hours, not 2 hours.

Dual pH probe and HMII A dual pH probe and/or HMII, not standard pH testing, can be performed in patients with LPRsymptoms, However, the minimum justification for antireflux surgery in patients whoundergo HMII is abnormal acid exposure in the distal esophagus with the pH monitor located5 cm proximal to the upper border of the LES.

BE, Barrett esophagus; HMII, hypopharyngeal multichannel intraluminal impedance; HRM, high-resolution manometry; LES, lower esophageal sphincter;LPR, laryngopharyngeal reflux; PPI, proton pump inhibitor; MII, multichannel intraluminal impedance; SAP, symptom association probability; SI, symptomindex.

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currently no data available to support the decision toproceed with antireflux surgery based on the results oforopharyngeal pH testing.The HMII-pH is a specialized impedance catheter that

has been introduced as a tool to directly measure refluxevents in the hypopharynx and proximal esophagus.53,54

The potential benefit of HMII-pH in detecting LPR eventshas been reported in the management of certain pulmo-nary and laryngeal conditions, such as end-stage lungdisease, adult-onset asthma, and chronic cough.53,77,78

However, there is a paucity of data supporting that theaddition of HMII-pH has improved patient selectionand outcomes of antireflux surgery. Well-designed,prospective studies with long-term follow-up are required.The Esophageal Diagnostic Advisory Panel did not

support making the decision to perform antireflux surgerybased on the results of either of these tests alone. TheEsophageal Diagnostic Advisory Panel agreed thata dual pH probe and/or MII-pH can be performed inpatients with LPR symptoms, however, the minimumjustification for antireflux surgery in patients who

undergo these studies is positive acid exposure in thedistal esophagus at a location 5 cm proximal to the upperborder of the LES as measured with manometry or upperendoscopy. The consensus of Esophageal DiagnosticAdvisory Panel was that these tests are promising, butobjective evidence of GERD as measured by standardesophageal physiology testing is still required before anti-reflux surgery.

CONCLUSIONSGastroesophageal reflux disease is a highly prevalentdisorder. Medical therapy improves symptoms in some,but not all patients. Antireflux surgery is a valid optionfor not only those with persistent symptoms, especiallypatients with volume regurgitation, but also those withcomplete symptomatic resolution on acid suppressivetherapy. However, proper patient selection is critical toobtain the best possible outcomes. For that reason, a panelof experts was assembled to review data and personalexperience with regard to the appropriate preoperativeevaluation for antireflux surgery. The consensus of

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Esophageal Diagnostic Advisory Panel is summarized inTable 3. Symptoms alone with or without PPI responseare not sufficient to support a diagnosis of GERD beforeantireflux surgery. Rather, objective esophageal testing isrequired to physiologically and anatomically evaluatethe presence and severity of GERD in all patients whoare considered for antireflux surgery. It is crucial to docu-ment the presence of abnormal distal esophageal acidexposure when antireflux surgery is considered, andreflux-related symptoms should be severe enough tooutweigh the potential side effects of fundoplication.Each testing modality has a specific role in the diagnosisand workup of GERD and no single test alone canprovide the entire clinical picture. The combined resultsof objective testing establish the presence of disease andassist with planning the operative approach. Currently,upper endoscopy, barium esophagram, pH testing, andmanometry are required for the preoperative evaluationfor antireflux surgery. Additional randomized studieswith long-term follow-up are required to evaluate thediagnostic and therapeutic benefit of new technologies,such as oropharyngeal pH testing and HMII-PH.

Author Contributions

Study conception and design: Jobe, RichterAcquisition of data: Jobe, Richter, HoppoAnalysis and interpretation of data: Peters, Bell, Dengler,DeVault, Fass, Gyawali, Kahrilas, Lacy, Pandolfino,Patti, Swanstrom, Kurian, Vela, Vaezi, DeMeester

Drafting of manuscript: Jobe, Hoppo, RichterCritical revision: Jobe, Richter, Hoppo, Peters, Bell,Dengler, DeVault, Fass, Gyawali, Kahrilas, Lacy,Pandolfino, Patti, Swanstrom, Kurian, Vela, Vaezi,DeMeester

REFERENCES

1. Isolauri J, Luostarinen M, Isolauri E, et al. Natural course ofgastroesophageal reflux disease: 17-22 year follow-up of 60patients. Am J Gastroenterol 1997;92:37e41.

2. Orlando RC. The pathogenesis of gastroesophageal refluxdisease: the relationship between epithelial defense, dysmotil-ity, and acid exposure. Am J Gastroenterol 1997;92[Suppl]:3Se5S; discussion 5S�7S.

3. Wiklund I. Review of the quality of life and burden ofillness in gastroesophageal reflux disease. Dig Dis 2004;22:108e114.

4. Moraes-Filho J, Cecconello I, Gama-Rodrigues J, et al. Brazil-ian consensus on gastroesophageal reflux disease: proposals forassessment, classification, and management. Am J Gastroen-terol 2002;97:241e248.

5. Vakil N, van Zanten SV, Kahrilas P, et al. The Montreal defi-nition and classification of gastroesophageal reflux disease:a global evidence-based consensus. Am J Gastroenterol 2006;101:1900e1920; quiz 1943.

6. Sontag SJ, O’Connell S, Khandelwal S, et al. Asthmatics withgastroesophageal reflux: long term results of a randomized trialof medical and surgical antireflux therapies. Am J Gastroen-terol 2003;98:987e999.

7. Raghu G. The role of gastroesophageal reflux in idiopathicpulmonary fibrosis. Am J Med 2003;115[Suppl 3A]:60Se64S.

8. El-Serag H, Becher A, Jones R. Systematic review: persistentreflux symptoms on proton pump inhibitor therapy in primarycare and community studies. Aliment Pharmacol Ther 2010;32:720e737.

9. Vakil N, Shaw M, Kirby R. Clinical effectiveness of laparo-scopic fundoplication in a US community. Am J Med 2003;114:1e5.

10. Dallemagne B, Weerts J, Markiewicz S, et al. Clinical results oflaparoscopic fundoplication at ten years after surgery. SurgEndosc 2006;20:159e165.

11. Morgenthal CB, Lin E, Shane MD, et al. Who will fail lapa-roscopic Nissen fundoplication? Preoperative prediction oflong-term outcomes. Surg Endosc 2007;21:1978e1984.

12. Johnson LF, DeMeester TR. Development of the 24-hourintraesophageal pH monitoring composite scoring system.J Clin Gastroenterol 1986;8:52e58.

13. Gerson LB, Kahrilas PJ, Fass R. Insights into gastroesophagealreflux disease-associated dyspeptic symptoms. Clin Gastroen-terol Hepatol 2011;9:824e833.

14. Lacy BE, Talley NJ, Locke GR 3rd, et al. Review article:current treatment options and management of functionaldyspepsia. Aliment Pharmacol Ther 2012;36:3e15.

15. DeMeester TR, Wang CI, Wernly JA, et al. Technique, indi-cations, and clinical use of 24 hour esophageal pH monitoring.J Thorac Cardiovasc Surg 1980;79:656e670.

16. Patti MG, Diener U, Tamburini A, et al. Role of esophagealfunction tests in diagnosis of gastroesophageal reflux disease.Dig Dis Sci 2001;46:597e602.

17. Stefanidis D, Hope WW, Kohn GP, et al. Guidelines forsurgical treatment of gastroesophageal reflux disease. SurgEndosc 2010;24:2647e2669.

18. Watson TJ, Peters JH. Evaluation of esophageal function forantireflux surgery. Gastrointest Endosc Clin N Am 2005;15:347e360.

19. Dent J, Vakil N, Jones R, et al. Accuracy of the diagnosis ofGORD by questionnaire, physicians and a trial of protonpump inhibitor treatment: the Diamond Study. Gut 2010;59:714e721.

20. Bytzer P, Jones R, Vakil N, et al. Limited ability of theproton-pump inhibitor test to identify patients with gastro-esophageal reflux disease. Clin Gastroenterol Hepatol 2012;10:1360e1366.

21. Fass R, Noelck N, Willis MR, et al. The effect of esomeprazole20 mg twice daily on acoustic and perception parameters of thevoice in laryngopharyngeal reflux. Neurogastroenterol Motil2010;22:134e141. e144�135.

22. Vaezi MF, Richter JE, Stasney CR, et al. Treatment of chronicposterior laryngitis with esomeprazole. Laryngoscope 2006;116:254e260.

23. Gasiorowska A, Poh CH, Fass R. Gastroesophageal refluxdisease (GERD) and irritable bowel syndrome (IBS)dis itone disease or an overlap of two disorders? Dig Dis Sci2009;54:1829e1834.

24. Richter JE, Pandolfino JE, Vela MF, et al. Utilization of wire-less pH monitoring technologies: a summary of the proceed-ings from the Esophageal Diagnostic Working Group. Dis

596 Jobe et al Preoperative Workup for Antireflux Surgery J Am Coll Surg

Esophagus 2012 Aug 7. http://dx.doi.org/10.1111/j.1442-2050.2012.01384.x [Epub ahead of print].

25. Eubanks TR, Omelanczuk P, Richards C, et al. Outcomes oflaparoscopic antireflux procedures. Am J Surg 2000;179:391e395.

26. Stein HJ, Barlow AP, DeMeester TR, Hinder RA. Complica-tions of gastroesophageal reflux disease. Role of the loweresophageal sphincter, esophageal acid and acid/alkaline expo-sure, and duodenogastric reflux. Ann Surg 1992;216:35e43.

27. DiBaise JK. The LA Classification for esophagitis: a call forstandardization. Am J Gastroenterol 1999;94:3403e3404.

28. Nasseri-Moghaddam S, Razjouyan H, Nouraei M, et al. Inter-and intra-observer variability of the Los Angeles classification:a reassessment. Arch Iran Med 2007;10:48e53.

29. Nwokediuko SC. Current trends in the management of gastro-esophageal reflux disease: a review. ISRN Gastroenterol 2012;2012:391631.

30. Sharma P, Dent J, Armstrong D, et al. The development andvalidation of an endoscopic grading system for Barrett’s esoph-agus: the Prague C & M criteria. Gastroenterology 2006;131:1392e1399.

31. Weston AP, Krmpotich P, Makdisi WF, et al. Short segmentBarrett’s esophagus: clinical and histological features, associ-ated endoscopic findings, and association with gastric intestinalmetaplasia. Am J Gastroenterol 1996;91:981e986.

32. Kahrilas PJ. The role of hiatus hernia in GERD. Yale J BiolMed 1999;72:101e111.

33. Treacy PJ, Jamieson GG. An approach to the management ofpara-oesophageal hiatus hernias. Aust N Z J Surg 1987;57:813e817.

34. Skinner DB, Belsey RH. Surgical management of esophagealreflux and hiatus hernia. Long-term results with 1,030patients. J Thorac Cardiovasc Surg 1967;53:33e54.

35. Mittal SK, Awad ZT, Tasset M, et al. The preoperativepredictability of the short esophagus in patients with strictureor paraesophageal hernia. Surg Endosc 2000;14:464e468.

36. Awad ZT, Mittal SK, Roth TA, et al. Esophageal shorteningduring the era of laparoscopic surgery. World J Surg 2001;25:558e561.

37. Zaninotto G, DeMeester TR, Schwizer W, et al. The loweresophageal sphincter in health and disease. Am J Surg 1988;155:104e111.

38. Kahrilas PJ, Dodds WJ, Hogan WJ, et al. Esophageal peri-staltic dysfunction in peptic esophagitis. Gastroenterology1986;91:897e904.

39. Patti MG, De Pinto M, de Bellis M, et al. Comparison of lapa-roscopic total and partial fundoplication for gastroesophagealreflux. J Gastrointest Surg 1997;1:309e314; discussion314�315.

40. Broeders JA, Sportel IG, Jamieson GG, et al. Impact of inef-fective oesophageal motility and wrap type on dysphagia afterlaparoscopic fundoplication. Br J Surg 2011;98:1414e1421.

41. Lacy BE, Dukowicz AC, Robertson DJ, et al. Clinical utility ofthe wireless pH capsule. J Clin Gastroenterol 2011;45:429e435.

42. Lacy BE, O’Shana T, Hynes M, et al. Safety and tolerability oftransoral Bravo capsule placement after transnasal manometryusing a validated conversion factor. Am J Gastroenterol 2007;102:24e32.

43. Tseng D, Rizvi AZ, Fennerty MB, et al. Forty-eight-hour pHmonitoring increases sensitivity in detecting abnormal

esophageal acid exposure. J Gastrointest Surg 2005;9:1043e1051; discussion 1051�1052.

44. Campos GM, Peters JH, DeMeester TR, et al. Multivariateanalysis of factors predicting outcome after laparoscopicNissen fundoplication. J Gastrointest Surg 1999;3:292e300.

45. Khajanchee YS, Hong D, Hansen PD, Swanstrom LL.Outcomes of antireflux surgery in patients with normal preop-erative 24-hour pH test results. Am J Surg 2004;187:599e603.

46. Agrawal A, Castell DO. Clinical importance of impedancemeasurements. J Clin Gastroenterol 2008;42:579e583.

47. Vela MF. Non-acid reflux: detection by multichannel intralu-minal impedance and pH, clinical significance and manage-ment. Am J Gastroenterol 2009;104:277e280.

48. Shay S, Tutuian R, Sifrim D, et al. Twenty-four hour ambu-latory simultaneous impedance and pH monitoring: a multi-center report of normal values from 60 healthy volunteers.Am J Gastroenterol 2004;99:1037e1043.

49. Zentilin P, Iiritano E, Dulbecco P, et al. Normal values of24-h ambulatory intraluminal impedance combined withpH-metry in subjects eating a Mediterranean diet. Dig LiverDis 2006;38:226e232.

50. Zerbib F, des Varannes SB, Roman S, et al. Normal values andday-to-day variability of 24-h ambulatory oesophagealimpedance-pH monitoring in a Belgian-French cohort of healthysubjects. Aliment Pharmacol Ther 2005;22:1011e1021.

51. del Genio G, Tolone S, del Genio F, et al. Prospective assess-ment of patient selection for antireflux surgery by combinedmultichannel intraluminal impedance pH monitoring.J Gastrointest Surg 2008;12:1491e1496.

52. Frazzoni M, Conigliaro R, Melotti G. Reflux parameters asmodified by laparoscopic fundoplication in 40 patients withheartburn/regurgitation persisting despite PPI therapy: a studyusing impedance-pH monitoring. Dig Dis Sci 2011;56:1099e1106.

53. Hoppo T, Sanz AF, Nason KS, et al. How much pharyngealexposure is “normal”? Normative data for laryngopharyngealreflux events using hypopharyngeal multichannel intraluminalimpedance (HMII). J Gastrointest Surg 2012;16:16e24;discussion 24�25.

54. Zerbib F, Roman S, Bruley Des Varannes S, et al. Normalvalues of pharyngeal and esophageal 24-hour pH impedancein individuals on and off therapy and interobserver reproduc-ibility. Clin Gastroenterol Hepatol 2013;11:366e372.

55. Francis DO, Goutte M, Slaughter JC, et al. Traditional refluxparameters and not impedance monitoring predict outcomeafter fundoplication in extraesophageal reflux. Laryngoscope2011;121:1902e1909.

56. Wiener GJ, Morgan TM, Copper JB, et al. Ambulatory 24-hour esophageal pH monitoring. Reproducibility and vari-ability of pH parameters. Dig Dis Sci 1988;33:1127e1133.

57. Weusten BL, Roelofs JM, Akkermans LM, et al. Thesymptom-association probability: an improved method forsymptom analysis of 24-hour esophageal pH data. Gastroen-terology 1994;107:1741e1745.

58. Singh S, Richter JE, Bradley LA, Haile JM. The symptom index.Differential usefulness in suspected acid-related complaints ofheartburn and chest pain. Dig Dis Sci 1993;38:1402e1408.

59. Broeders JA, Draaisma WA, Bredenoord AJ, et al. Oesopha-geal acid hypersensitivity is not a contraindication to Nissenfundoplication. Br J Surg 2009;96:1023e1030.

Vol. 217, No. 4, October 2013 Jobe et al Preoperative Workup for Antireflux Surgery 597

60. Kavitt RT, Higginbotham T, Slaughter JC, et al. Symptomreports are not reliable during ambulatory reflux monitoring.Am J Gastroenterol 2012;107:1826e1832.

61. Slaughter JC, Goutte M, Rymer JA, et al. Caution about over-interpretation of symptom indexes in reflux monitoring forrefractory gastroesophageal reflux disease. Clin GastroenterolHepatol 2011;9:868e874.

62. Abell TL, Camilleri M, Donohoe K, et al. Consensus recom-mendations for gastric emptying scintigraphy: a joint report ofthe American Neurogastroenterology and Motility Society andthe Society of Nuclear Medicine. Am J Gastroenterol 2008;103:753e763.

63. Lacy BE. Functional dyspepsia and gastroparesis: one diseaseor two? Am J Gastroenterol 2012;107:1615e1620.

64. Bais JE, Samsom M, Boudesteijn EA, et al. Impact of delayedgastric emptying on the outcome of antireflux surgery. AnnSurg 2001;234:139e146.

65. Farrell TM, Richardson WS, Halkar R, et al. Nissen fundopli-cation improves gastric motility in patients with delayed gastricemptying. Surg Endosc 2001;15:271e274.

66. Viljakka M, Saali K, Koskinen M, et al. Antireflux surgeryenhances gastric emptying. Arch Surg 1999;134:18e21.

67. Tougas G, Eaker EY, Abell TL, et al. Assessment of gastricemptying using a low fat meal: establishment of internationalcontrol values. Am J Gastroenterol 2000;95:1456e1462.

68. Wayman J, Myers JC, Jamieson GG. Preoperative gastricemptying and patterns of reflux as predictors of outcome afterlaparoscopic fundoplication. Br J Surg 2007;94:592e598.

69. Koufman JA, Amin MR, Panetti M. Prevalence of reflux in113 consecutive patients with laryngeal and voice disorders.Otolaryngol Head Neck Surg 2000;123:385e388.

70. Barry DW, Vaezi MF. Laryngopharyngeal reflux: more ques-tions than answers. Cleve Clin J Med 2010;77:327e334.

71. Ford CN. Evaluation and management of laryngopharyngealreflux. JAMA 2005;294:1534e1540.

72. Gatta L, Vaira D, Sorrenti G, et al. Meta-analysis: the efficacyof proton pump inhibitors for laryngeal symptoms attributedto gastro-oesophageal reflux disease. Aliment Pharmacol Ther2007;25:385e392.

73. Qadeer MA, Phillips CO, Lopez AR, et al. Proton pumpinhibitor therapy for suspected GERD-related chronic laryn-gitis: a meta-analysis of randomized controlled trials. Am JGastroenterol 2006;101:2646e2654.

74. Sun G, Muddana S, Slaughter JC, et al. A new pH catheter forlaryngopharyngeal reflux: normal values. Laryngoscope 2009;119:1639e1643.

75. Ummarino D, Vandermeulen L, Roosens B, et al. Gastro-esophageal reflux evaluation in patients affected by chroniccough: Restech versus multichannel intraluminal impedance/pH metry. Laryngoscope 2013;123:980e984.

76. Vailati C, Mazzoleni G, Bondi S, et al. Oropharyngeal pHmonitoring for laryngopharyngeal reflux: is it a reliable testbefore therapy? J Voice 2013;27:84e89.

77. Hoppo T, Jarido V, Pennathur A, et al. Antirefluxsurgery preserves lung function in patients with gastro-esophageal reflux disease and end-stage lung disease beforeand after lung transplantation. Arch Surg 2011;146:1041e1047.

78. Komatsu Y, Hoppo T, Jobe BA. Proximal reflux as a cause ofadult-onset asthma: the case for hypopharyngeal impedancetesting to improve the sensitivity of diagnosis. JAMA Surg2013;148:50e58.