Surg Endosc (2008) 22:2518–2523 DOI 10.1007/s00464-008-9958-0
NEW TECHNOLOGY
Total fundoplication controls acid and nonacid reflux: evaluation by pre- and postoperative 24-h pH–multichannel intraluminal impedance Gianmattia del Genio Æ Salvatore Tolone Æ Federica del Genio Æ Gianluca Rossetti Æ Luigi Brusciano Æ Francesco Pizza Æ Landino Fei Æ Alberto del Genio
Received: 6 January 2008 / Accepted: 10 April 2008 / Published online: 14 May 2008 Ó Springer Science+Business Media, LLC 2008
Abstract Background Studies have demonstrated that Nissen fundoplication controls acid gastroesophageal reflux (GER). Combined 24-h pH and multichannel intraluminal impedance (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, 15 consecutive 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 calculated with the patient in both upright and recumbent positions. Results The 24-h pH monitoring confirmed the postoperative 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 fundoplication in controlling both acid and nonacid GER. Keywords Fundoplication GERD MII-ph pH monitoring
G. del Genio (&) S. Tolone F. del Genio G. Rossetti L. Brusciano F. Pizza L. Fei A. del Genio First Division of General and Gastrointestinal Surgery, Second University of Naples, via Pansini, 5, 80131 Naples, Italy e-mail:
[email protected]
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Nissen fundoplication currently is the most popular surgical 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 esophagogastric 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 associated 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 24 h 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 NissenRossetti 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 documentation 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.
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Materials and methods
2519 Table 2 Clinical assessment by the modified DeMeester scoring system before and after surgery
From July 1, 2005, 15 consecutive patients (8 women and 7 men; mean age, 43.7 ± 14.5 years; range, 22–65 years) underwent laparoscopic Nissen-Rossetti fundoplication at the First Division of General and Gastrointestinal Surgery of the Second University of Naples. Patients who for at least 12 months 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 (Table 1). The surgical technique used has already been described [7]. In short, a 2- cm Nissen-Rossetti fundoplication was performed laparoscopically with extensive transhiatal mobilization of the esophagus and preservation of short gastrics. Fundoplication was calibrated by intraoperative manometry at 20 to 40 mmHg. No esophageal bougie was used for calibration of the valve. An intraoperative endoscope controlled the wrap. The demographic data are detailed in Table 2.
Preoperative(n = 15) Postoperative(n = 15) Heartburn
2.3 ± 0.8
0.2 ± 0.2a
Acid regurgitation
1.8 ± 0.9
0.3 ± 0.2a
Chest pain
1.6 ± 0.8
0.3 ± 0.2a
Respiratory complication
1.1 ± 0.9
0.3 ± 0.1a
Solid food dysphagia
1.4 ± 0.5
0.4 ± 0.1a
a
p \ 0.05
Before subjects entered the study, a specific informed consent was obtained from each. The exclusion criteria specified paraesophageal (type 2), mixed (type 3), or giant ([5 cm) hernias; Barrett’s esophagus; and a history of abdominal surgery. Statistical analysis was performed using SPSS for Windows (version 12.0; 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 than 0.05 were considered statistically significant. Instrumental assessment
Table 1 Modified DeMeester scoring system Symptoms
Score Description
Dysphagia
0
None
1
Occasional transient episodes
2
Liquids required to clear
Heartburn
3
Impaction requiring medical attention
0
None
1
Occasional brief episodes
2
Frequent episodes requiring medical treatment Interference with daily activities
3 Regurgitation
Chest pain
Respiratory complications
0
None
1
Occasional brief episodes
2
Episodes predictable by posture
3
Interference with daily activities
0
None
1
Occasional brief episodes
2
Frequent episodes requiring medical treatment
3
Interference with daily activities
0
None
1 2
Occasional brief episodes Frequent episodes requiring medical treatment
3
Interference with daily activities
Preoperatively, 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 at 90° to each other and four positioned longitudinally at intervals of 5 cm. The catheter was perfused with distilled water using a low-compliance capillary pump at a constant infusion rate of 0.8 ml/min at 1.2 kg/cm2. A system of pressure transducers transmitted data to an acquisition device (ACQ1TM; Menfis Biomedical, Bologna, Italy) and analyzed the data using specific software (Dyno 2000TM; Menfis BioMedica). The following variables were assessed: location and pressure of the lower esophageal sphincter (LES), relaxation of the LES in response to swallowing, and the amplitude and propagation of peristalsis (esophageal peristalsis less than 30 mmHg indicated impairment). The LES was studied using the stationary pull-through method. Combined multichannel intraluminal impedance and 24-h pH All proton pump inhibitor, prokinetics or any other drugs effective for GER had to be stopped at least 7 to 8 days before MII-pH. A dedicated catheter (Sandhill Scientific Inc., Highlands Ranch, CO, USA) with a pH sensor 5 cm
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above the LES/fundoplication and six pairs of impedance sensors positioned in the esophagus 3, 5, 7, 9, 15, and 17 cm 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 24 h. The patients were invited to go through a ‘‘normal’’ activity and diet. They were invited to register the symptoms 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 Analysis 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,
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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 waveforms 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 30 s and an esophageal retrograde movement was in the same area of measurement (mimicking a GER) (Fig. 2B), ‘‘intraesophageal reflux’’ in the case of an esophageal retrograde movement not detected by the two most distal impedance channels (channels 5 and 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 movement (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].
Results
Fig. 1 A 24-h pH-multichannel intraluminal impedance (MII-pH) catheter with the six impedance segments and the pH sensor 5 cm above the fundoplication
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The evaluations were performed a median of 15 days (range, 2–45 days) before the fundoplication and 7 months (range, 5–12 months) afterward. All the preoperative evaluations showed a normal peristalsis with 100% complete LES relaxations. The mean LES pressure was 8.1 ± 3.6 mmHg preoperatively and 28.6 ± 5.2 mmHg 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 ± 62 min) and postoperative (1,267 ± 126 min) groups. The mean registration for the recumbent position was similar in the preoperative (580 ± 204) and postoperative (535 ± 197) groups. The preoperative (65.8 ± 5.1 kg) and postoperative (62.6 ± 7.2 kg) 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 retrograde movements. Table 3 summarizes the total acid and nonacid GER episodes detected by MII-pH. The Nissen antireflux
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Fig. 2 Postoperative waveform types of the episodes detected as nonacid GER by Autoscan. (A) Nonacid GER. (B) Swallowinduced retrograde movement. (C) Intraesophageal retrograde movement. (D) No reflux
procedure 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 symptom index ([50%) by combined MII-pH for 12 of the 15 patients. Postoperatively, symptom occurrence fell considerably (Table 2). None of the patients had a positive symptom index. The proportion of physical reflux characteristics (liquid, mixed, gas) did not change after surgery.
Discussion Current gastroenterologic research investigating GERD is focused primarily on finding effective drugs for patients
not 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. However, 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 antireflux 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 competence [7]. There is no reason to suspect that after the
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Fig. 3 Total, acid, and nonacid reflux episodes detected in upright and recumbent positions
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procedure 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 candidates 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 surprisingly 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 fundoplication, 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 retrograde 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 fundoplication controls both acid and nonacid GER as measured using MII-pH. Appropriate preoperative investigation and selection are important for securing good results.
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Table 3 Pre- and postoperative detailed findings at 24-h combined multichannel intraluminal impedance and pH (MII-pH) Preoperative(n = 15)
Postoperative(n = 15)
% Time pH \4 total
5.9 ± 2.9
0.4 ± 0.3a
% Time pH \4 upright
6.5 ± 3.5
0.7 ± 0.8a
% Time pH \4 recumbent
3.3 ± 2.5
0.2 ± 0.2a
Number of reflux (pH)
33.5 ± 15.7
2.0 ± 1.5a
DeMeester score (pH)
17.4 ± 8.5
1.6 ± 1.5a
Mean ± SD
Median (25th–75th)
Mean ± SD a
Median (25th–75th) 5 (5–12)
All reflux total (MII)
65.2 ± 45.4
47 (31–79)
10 ± 10
All reflux upright (MII)
53.1 ± 43.0
36 (22–60)
5.1 ± 6.0a
2 (1–7)
a
All reflux recumbent (MII)
12.1 ± 5.0
11 (9–15)
4.9 ± 7.3
3 (2–3)
Acid reflux total (MII)
33.4 ± 21.4
30 (18–40)
1.6 ± 3.6a
0 (0–1)
Acid reflux upright (MII)
26.5 ± 21.0
23 (15–39)
1.3 ± 3.6a
0 (0–0)
6.9 ± 6.0
6 (3–10)
0.3 ± 0.8a
0 (0–0)
31.8 ± 34.1
17 (13–33)
8.3 ± 9.3a
5 (3–11)
26.7 ± 34.2
15 (10–27)
a
3.8 ± 3.6
2 (1–7)
5.1 ± 3.7
4 (3–6)
4.6 ± 7.4
2 (2–3)
Acid reflux recumbent (MII) Nonacid reflux total (MII) Nonacid reflux upright (MII) Nonacid reflux recumbent (MII) a
p \ 0.05
Acknowledgments Special thanks go to Susanna Capasso (Biologist, 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.
References 1. del Genio A, Maffettone V, Izzo G (1991) Intraoperative esophageal manometry. Minerva Chir 46:201–210 2. Zentilin P, Iiritano E, Dulbecco P, Giannini E, Savarino V (2006) Normal values of 24-h ambulatory intraluminal impedance combined with pH-metry in subjects eating a Mediterranean diet. Dig Liver Dis 38:226–232 3. 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 multicenter report of normal values from 60 healthy volunteers. Am J Gastroenterol 99:1037–1043 4. Mainie I, Tutuian R, Shay S, Vela M, Zhang X, Sifrim D, Castell DO (2006) Acid and nonacid reflux in patients with persistent symptoms despite acid suppressive therapy: a multicentre study using combined ambulatory impedance-pH monitoring. Gut 55:1398–1402 5. 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 Surg 94:48–52 6. Gruebel C, Linke G, Tutuian R, Hebbard G, Zerz A, Meyenberger C, Borovicka J (2007) Prospective study examining the impact of multichannel intraluminal impedance on antireflux surgery. Surg Endosc 22:1241–1247
7. 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 Surg 31:1099–1106 8. Wiener GJ, Richter JE, Copper JB, Wu WC, Castell DO (1988) The symptom index: a clinically important parameter of ambulatory 24-hour esophageal pH monitoring. Am J Gastroenterol 83:358–361 9. DeMeester TR, Johnson LF (1975) Evaluation of the Nissen antireflux procedure by esophageal manometry and twenty-fourhour pH monitoring. Am J Surg 129:94–100 10. 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 17:1050–1054 11. Okholm M, Sorensen H, Wallin L, Boesby S (1999) Bile reflux into the esophagus: Bilitec 2000 measurements in normal subjects and in patients after Nissen fundoplication. Scand J Gastroenterol 34:653–657 12. Mainie I, Castell DO (2006) Do we need to rethink fundoplication for patients who have failed proton pump inhibitor therapy? Nat Clin Pract Gastroenterol Hepatol 3:2–3 13. Roman S, Bruley des Varannes S, Pouderoux P, Chaput U, Mion F, 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 automatic analysis for gastro-oesophageal reflux assessment. Neurogastroenterol Motil 18:978–986
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