Total Fundoplication Controls Acid & Nonacid Reflux-del Genio 2008

NEW TECHNOLOGYTotal fundoplication controls acid and nonacid reflux:evaluation by pre-and postoperative 24-h pH–multichannel intraluminal impedanceGianmattia del Genio ÆSalvatore Tolone ÆFederica del Genio ÆGianluca Rossetti ÆLuigi Brusciano ÆFrancesco Pizza ÆLandino Fei ÆAlberto del GenioReceived:6January 2008/Accepted:10April 2008ÓSpringer Science+Business Media,LLC 2008AbstractBackground Studies have demonstrated that Nissen fun-doplication controls acid gastroesophageal reflux (GER).Combined 24-h pH and multichannel intraluminal imped-ance (MII-pH)allows detection of both acid and nonacid GER.Antireflux surgery is considered for any patient whose medical therapy is not efficient,particularly patients with nonacid gastroesophageal reflux disease (GERD).Nevertheless,fundoplication used to control nonacid reflux has not been reported to date.Methods In this study,15consecutive patients who underwent laparoscopic Nissen-Rossetti fundoplication had MII-pH both before and after the surgical procedure.The numbers of acid and nonacid GER episodes were calcu-lated with the patient in both upright and recumbent positions.Results The 24-h pH monitoring confirmed the postop-erative reduction of exposure to acid (p \0.05).Postoperatively,the total,acid,and nonacid numbers of GER episodes were reduced (p \0.05).Conclusion According to the findings,MII-pH is feasible and well tolerated.It provides an objective means for evaluating the effectiveness of Nissen-Rossetti fundopli-cation in controlling both acid and nonacid GER.Keywords Fundoplication ÁGERD ÁMII-ph ÁpH monitoringNissen fundoplication currently is the most popular surgi-cal procedure for the treatment of gastroesophageal reflux disease (GERD).It is assumed that creation of a new 360°high-pressure zone restores the competence of the esoph-agogastric junction,thus eliminating both acid and nonacid gastroesophageal reflux (GER)[1].However,this concept has been supported for years only by indirect observation of postoperative healing for every type of symptom asso-ciated with GER independently of its acidic or nonacidic nature.Combined multichannel intraluminal impedance and pH (MII-pH)is the most sophisticated instrument for studying GER.Over 24h of monitoring,it enables detection of every antegrade or retrograde movement into the esophagus.Furthermore,using a pH sensor located in the catheter,each movement can be assigned a degree of acidity.Using this technology,some authors recently have established the normal values for healthy volunteers [2,3]and described the patterns for patients with GERD [4]Recently,Roman et al.[5]reported the postoperative MII-pH evaluation of patients who underwent Nissen-Rossetti fundoplication.Grubel et al.[6]performed a pre-and postoperative study of patients who underwent an uncommon procedure (anterior fundophrenicopexy and mesh-augmented hiatoplasty).However,no pre-or postoperative evaluation of fundoplication has been reported to date.We undertook the current study to evaluate by means of MII-pH the efficacy of fundoplication in controlling acid and nonacid GER.An objective doc-umentation of the worth of the antireflux procedures may be helpful in refining the correct indications of the surgical therapy and the usefulness of MII-pH for surgery candidates.G.del Genio (&)ÁS.Tolone ÁF.del Genio ÁG.Rossetti ÁL.Brusciano ÁF.Pizza ÁL.Fei ÁA.del GenioFirst Division of General and Gastrointestinal Surgery,Second University of Naples,via Pansini,5,80131Naples,Italy e-mail:gdg@Surg EndoscDOI 10.1007/s00464-008-9958-0Materials and methodsFrom July1,2005,15consecutive patients(8women and7 men;mean age,43.7±14.5years;range,22–65years) underwent laparoscopic Nissen-Rossetti fundoplication at the First Division of General and Gastrointestinal Surgery of the Second University of Naples.Patients who for at least12months had experienced typical or atypical symptoms requiring daily medical therapy for symptom control and those not responding to medical therapy were offered the alternative of continuing with medical therapy or undergoing antireflux surgery.Evaluation of the symptoms was accomplished by a standardized questionnaire based on the modified DeMeester symptom scoring system(Table1).The sur-gical technique used has already been described[7].In short,a2-cm Nissen-Rossetti fundoplication was per-formed laparoscopically with extensive transhiatal mobilization of the esophagus and preservation of short gastrics.Fundoplication was calibrated by intraoperative manometry at20to40mmHg.No esophageal bougie was used for calibration of the valve.An intraoperative endoscope controlled the wrap.The demographic data are detailed in Table2.Before subjects entered the study,a specific informed consent was obtained from each.The exclusion criteria specified paraesophageal(type2),mixed(type3),or giant ([5cm)hernias;Barrett’s esophagus;and a history of abdominal surgery.Statistical analysis was performed using SPSS for Windows(version12.0;SPSS Inc.,Chicago,IL,USA). The results are expressed as mean±standard deviation unless otherwise indicated.Student’s t-test,the chi-square test,and Fischer’s exact test were used as appropriate.The p values were calculated from the means,and all p values less than0.05were considered statistically significant.Instrumental assessmentPreoperatively,all patients underwent upper endoscopy, esophageal manometry,and MII-pH.Stationary esophageal manometry was performed using eight channel-perfusion catheters:four positioned radially and oriented at90°to each other and four positioned longitudinally at intervals of5cm.The catheter was perfused with distilled water using a low-compliance capillary pump at a constant infusion rate of0.8ml/min at1.2kg/cm2.A system of pressure trans-ducers transmitted data to an acquisition device (ACQ1TM;Menfis Biomedical,Bologna,Italy)and ana-lyzed the data using specific software(Dyno2000TM; Menfis BioMedica).The following variables were asses-sed:location and pressure of the lower esophageal sphincter(LES),relaxation of the LES in response to swallowing,and the amplitude and propagation of peri-stalsis(esophageal peristalsis less than30mmHg indicated impairment).The LES was studied using the stationary pull-through method.Combined multichannel intraluminal impedance and24-h pHAll proton pump inhibitor,prokinetics or any other drugs effective for GER had to be stopped at least7to8days before MII-pH.A dedicated catheter(Sandhill Scientific Inc.,Highlands Ranch,CO,USA)with a pH sensor5cmTable1Modified DeMeester scoring systemSymptoms Score DescriptionDysphagia0None1Occasional transient episodes2Liquids required to clear3Impaction requiring medical attention Heartburn0None1Occasional brief episodes2Frequent episodes requiring medicaltreatment3Interference with daily activities Regurgitation0None1Occasional brief episodes2Episodes predictable by posture3Interference with daily activities Chest pain0None1Occasional brief episodes2Frequent episodes requiring medicaltreatment3Interference with daily activitiesRespiratory complications 0None1Occasional brief episodes2Frequent episodes requiring medicaltreatment3Interference with daily activitiesTable2Clinical assessment by the modified DeMeester scoringsystem before and after surgeryPreoperative(n=15)Postoperative(n=15)Heartburn 2.3±0.80.2±0.2aAcid regurgitation 1.8±0.90.3±0.2aChest pain 1.6±0.80.3±0.2aRespiratorycomplication1.1±0.90.3±0.1aSolid food dysphagia 1.4±0.50.4±0.1aa p\0.05Surg Endoscabove the LES/fundoplication and six pairs of impedance sensors positioned in the esophagus 3,5,7,9,15,and 17cm above the upper limit of the high-pressure zone was placed transnasally (Fig.1).The data were transmitted by the catheter into a software program included in the device (Sleuth;Sandhill Scientific,Inc.)worn by the patient for 24h.The patients were invited to go through a ‘‘normal’’activity and diet.They were invited to register the symp-toms carefully into the device by digital input and to note on a prescribed paper form the meal periods,the time they spent in the recumbent position,and every symptom that occurred.All subjects tolerated the procedure well without complications.Data were analyzed using the Bioview GERD Anal-ysis Software (Sandhill Scientific Inc.).Meal periods and swallows were excluded from the analysis.All tracings were reviewed individually to verify the correspondence between the result of the computer evaluation (Autoscan,Bioview GERD Analysis Software;Sandhill Scientific,Inc.,Highlands Ranch,CO,USA)and the morphology of every single reflux episode by one investigator (G.d.G.).After a careful analysis of these episodes,we were able to distinguish four different types of postoperative wave-forms detected by Autoscan:‘‘nonacid reflux’’in the case of a true nonacid GER (Fig.2A),‘‘swallow-induced reflux’’if a swallow occurred in the preceding 30s and an esophageal retrograde movement was in the same area of measurement (mimicking a GER)(Fig.2B),‘‘intraesoph-ageal reflux’’in the case of an esophageal retrograde movement not detected by the two most distal impedance channels (channels 5and 6)(Fig.2C),and ‘‘no retrograde movement’’if the automatic software detected an area without significance or not corresponding to a nonacid reflux,swallow-induced reflux,or intraesophageal move-ment (Fig.2D).The symptom index was calculated as the percentage of symptoms preceded by a reflux event detected by MII.A positive symptom index was defined as one of 50%or more (i.e.,at least half of the events were preceded by reflux)[8].ResultsThe evaluations were performed a median of 15days (range,2–45days)before the fundoplication and 7months (range,5–12months)afterward.All the preoper-ative evaluations showed a normal peristalsis with 100%complete LES relaxations.The mean LES pressure was 8.1±3.6mmHg preoperatively and 28.6±5.2mmHg postoperatively.The pre-and postoperative modified DeMeester symptom scoring system is reported in Table 2.The mean MII-pH time of monitoring was not different between the preoperative (1,223±62min)and postoper-ative (1,267±126min)groups.The mean registration for the recumbent position was similar in the preoperative (580±204)and postoperative (535±197)groups.The preoperative (65.8±5.1kg)and postoperative (62.6±7.2kg)weights were essentially the same.A comparison of the pre-and postsurgical 24-h pH monitoring results is shown in Table 3.In the postoperative group,542(mean,39.3±17.6)nonacid reflux episodes were automatically detected by the Autoscan.Of these,36(6.6%)corresponded to true nonacid reflux,242(44.6%)to swallow-induced reflux,98(18.1%)to intraesophageal reflux retrograde movements,and 166(30.6%)to no ret-rograde movements.Table 3summarizes the total acid and nonacid GER episodes detected by MII-pH.The NissenantirefluxFig.1A 24-h pH-multichannel intraluminal impedance (MII-pH)catheter with the six impedance segments and the pH sensor 5cm above the fundoplicationSurg Endoscprocedure produced an improvement in all categories of the MII-pH over the patients’preoperative values.The overall number of GER episodes was statistically reduced in both the upright and recumbent positions (p \0.05).This reduction was obtained due to the postoperative control of both the acid (p \0.05)and nonacid (p \0.05)GER episodes (Fig.3).The preoperative symptoms showed a positive symp-tom index ([50%)by combined MII-pH for 12of the 15patients.Postoperatively,symptom occurrence fell con-siderably (Table 2).None of the patients had a positive symptom index.The proportion of physical reflux char-acteristics (liquid,mixed,gas)did not change after surgery.DiscussionCurrent gastroenterologic research investigating GERD is focused primarily on finding effective drugs for patientsnot responding to proton pump inhibitors.It is likely that a large portion of these patients are affected by transient lower esophageal sphincter relaxation,nonacid reflux episodes,or both [4].Currently,the most effective treatment for these patients is antireflux surgery.How-ever,although the effects of fundoplication in eliminating acid reflux [9]and preventing occurrences of transient lower esophageal sphincter relaxation [10]had been reported,its role on nonacid reflux blocking had not been clarified [11].Data from this study clearly demonstrate that the an-tireflux wrap acts as an effective functional barrier capable of protecting the esophageal mucosa from both the acid and nonacid GER events,and that this reduction was obtained in both the upright and recumbent positions.This complete protective effect is not surprising.Indeed,the Nissen procedure increases the distal esophageal sphincter pressure to a height three times the preoperative levels and restores the esophagogastric junction compe-tence [7].There is no reason to suspect that aftertheFig.2Postoperative waveform types of the episodes detected as nonacid GER by Autoscan.(A )Nonacid GER.(B )Swallow-induced retrograde movement.(C )Intraesophageal retrograde movement.(D )No refluxSurg Endoscprocedure for these patients the acid GER disappears (at pH monitoring)whereas the nonacid GER remains unchanged.This is consistent with the recent observation of Mainie and Castell [12]on the potential worth of fundoplication for patients not responsive to a proton pump inhibitor with a MII-pH positive for nonacid GER.Furthermore,the MII-pH was a well-tolerated procedure in both the pre-and postoperative settings but added more information than the traditional pH monitoring (e.g.,nonacid reflux).Therefore,we suggest its routine use for selecting and following up the candidates for antireflux surgery.If confirmed by more extensive evaluations,the data of this study may have important clinical implications.Because fundoplication can control also the nonacid reflux,the diagnostic role of MII-pH to identify the correct can-didates for surgery is crucial.Indeed,a patient unresponsive to proton pump inhibitors with a pathologic number of nonacid reflux or a positive correlation of the symptoms with nonacid type GER events can be sent to surgery with an objective indication.For this reason,the mean preoperative DeMeester score may appear surpris-ingly low.Moreover,the data of this study highlight the fact that patients not responsive to medical treatment and with a diagnosis of nonacid GER at MII-pH need to be addressed with an antireflux procedure until new effective drugs become available.Notably,although the automatic analysis software (Autoscan)is reliable for evaluating patients with GERD [13],it has some limitations for analyzing tracing from patients who underwent surgery.This is mainly due to the complexity of the MII waveforms generated above the fundoplication.Indeed,in the presence of the fundoplica-tion,the liquid bolus pushed by the force generated from the pharyngeal pump progresses rapidly down because it encounters the antireflux wrap.Here,the tail of the liquid swallow undergoes a change of direction forced by the high-pressure zone of the fundoplication (retrograde escape),which we have called the ‘‘phenomenon of the tail inversion.’’The MII-pH software is not able to discern these retro-grade movements above the fundoplication from the true nonacid GER episodes,so a careful manual analysis is mandatory.Another bias of the study results from the short interval between the surgical procedure and the MII-pH postoperative evaluation.In summary,data from this study confirm that fun-doplication controls both acid and nonacid GER as measured using MII-pH.Appropriate preoperative investigation and selection are important for securing goodresults.Fig.3Total,acid,and nonacid reflux episodes detected in upright and recumbent positionsSurg EndoscAcknowledgments Special thanks go to Susanna Capasso(Biolo-gist,Medimar)for her continuous technical support and to the continuous work of Vincenzo Maffettone,M.D.,PhD,Vincenzo Napolitano,M.D.,PhD,Federica Russo,M.D.,and Maria Di Martino, M.D.,in collecting the data and daily assisting the patients. References1.del Genio A,Maffettone V,Izzo G(1991)Intraoperativeesophageal manometry.Minerva Chir46:201–2102.Zentilin P,Iiritano E,Dulbecco P,Giannini E,Savarino V(2006)Normal values of24-h ambulatory intraluminal impedance combined with pH-metry in subjects eating a Mediterranean diet.Dig Liver Dis38:226–2323.Shay S,Tutuian R,Sifrim D,Vela M,Wise J,Balaji N,Zhang X,Adhami T,Murray J,Peters J,Castell D(2004)Twenty-four-hour ambulatory simultaneous impedance and pH monitoring:a mul-ticenter report of normal values from60healthy volunteers.Am J Gastroenterol99:1037–10434.Mainie I,Tutuian R,Shay S,Vela M,Zhang X,Sifrim D,CastellDO(2006)Acid and nonacid reflux in patients with persistent symptoms despite acid suppressive therapy:a multicentre study using combined ambulatory impedance-pH monitoring.Gut 55:1398–14025.Roman S,Poncet G,Serraj I,Zerbib F,Boulez J,Mion F(2007)Characterization of reflux events after fundoplication using combined impedance-pH recording.Br J Surg94:48–526.Gruebel C,Linke G,Tutuian R,Hebbard G,Zerz A,Meyen-berger C,Borovicka J(2007)Prospective study examining the impact of multichannel intraluminal impedance on antireflux surgery.Surg Endosc22:1241–12477.del Genio G,Rossetti G,Brusciano L,Limongelli P,Pizza F,Tolone S,Fei L,Maffettone V,Napolitano V,del Genio A(2007) Laparoscopic Nissen-Rossetti fundoplication with routine use of intraoperative endoscopy and manometry:technical aspects of a standardized technique.World J Surg31:1099–11068.Wiener GJ,Richter JE,Copper JB,Wu WC,Castell DO(1988)The symptom index:a clinically important parameter of ambu-latory24-hour esophageal pH monitoring.Am J Gastroenterol 83:358–3619.DeMeester TR,Johnson LF(1975)Evaluation of the Nissenantireflux procedure by esophageal manometry and twenty-four-hour pH monitoring.Am J Surg129:94–10010.Bahmeriz F,Dutta S,Allen CJ,Pottruff CG,Anvari M(2003)Does laparoscopic antireflux surgery prevent the occurrence of transient lower esophageal sphincter relaxation?Surg Endosc 17:1050–105411.Okholm M,Sorensen H,Wallin L,Boesby S(1999)Bile refluxinto the esophagus:Bilitec2000measurements in normal subjects and in patients after Nissen fundoplication.Scand J Gastroenterol 34:653–65712.Mainie I,Castell DO(2006)Do we need to rethink fundoplica-tion for patients who have failed proton pump inhibitor therapy?Nat Clin Pract Gastroenterol Hepatol3:2–313.Roman S,Bruley des Varannes S,Pouderoux P,Chaput U,MionF,Galmiche JP,Zerbib F Consortium de Recherche Inde´pendant sur le Traitement et l’Exploration du Reflux gastro-oesophagien et de l’Endobrachyoesophage(CRITERE)(2006)Ambulatory 24-h esophageal impedance-pH recordings:reliability of auto-matic analysis for gastro-oesophageal reflux assessment.Neurogastroenterol Motil18:978–986Table3Pre-and postoperative detailedfindings at24-h combined multichannel intraluminal impedance and pH(MII-pH)Preoperative(n=15)Postoperative(n=15)%Time pH\4total 5.9±2.90.4±0.3a%Time pH\4upright 6.5±3.50.7±0.8a%Time pH\4recumbent 3.3±2.50.2±0.2aNumber of reflux(pH)33.5±15.7 2.0±1.5aDeMeester score(pH)17.4±8.5 1.6±1.5aMean±SD Median(25th–75th)Mean±SD Median(25th–75th)All reflux total(MII)65.2±45.447(31–79)10±10a5(5–12)All reflux upright(MII)53.1±43.036(22–60) 5.1±6.0a2(1–7)All reflux recumbent(MII)12.1±5.011(9–15) 4.9±7.3a3(2–3)Acid reflux total(MII)33.4±21.430(18–40) 1.6±3.6a0(0–1)Acid reflux upright(MII)26.5±21.023(15–39) 1.3±3.6a0(0–0)Acid reflux recumbent(MII) 6.9±6.06(3–10)0.3±0.8a0(0–0)Nonacid reflux total(MII)31.8±34.117(13–33)8.3±9.3a5(3–11)Nonacid reflux upright(MII)26.7±34.215(10–27) 3.8±3.6a2(1–7)Nonacid reflux recumbent(MII) 5.1±3.74(3–6) 4.6±7.42(2–3)a p\0.05Surg Endosc。