Endoscopic treatment modalities for GERD: Technologic score or scare?
2001; Elsevier BV; Volume: 53; Issue: 4 Linguagem: Inglês
10.1067/mge.2001.113917
ISSN1097-6779
Autores Tópico(s)Helicobacter pylori-related gastroenterology studies
ResumoSee Articles p. 407, 416, 423. Gastroesophageal reflux disease (GERD) has forged a commanding presence in clinical practice. Medical treatment with potent antacid medication or the surgical treatment with laparoscopic fundoplication appeared to be firmly established as the future therapeutic modalities for GERD and its complications. Not so, apparently! At Digestive Disease Week 2000 in San Diego, the latest technologic advances relevant to GI disorders were on display. One of the “hottest” technologic areas was the endoscopic treatment of GERD. A packed house was present for a 90-minute symposium1Lehman GA Hinder RA DDW combined clinical symposium: innovations in management of GERD [listed presentation].Gastroenterology. 2000; 118: 199Google Scholar devoted to this subject that sounded, initially, like a home economics course, that is, perendoscopic baking, sewing, and stuffing the gullet to prevent GERD! The pursuit of endoscopic treatments of GERD is not new. Endoscopic methods of altering the anatomy of the cardioesophageal junction in an attempt to prevent gastric reflux date back over a decade. This research conducted by both medical and surgical investigators has predominantly involved animal models with varying success. A variety of endoscopic techniques directed toward altering the structures at the gastroesophageal junction (GEJ) to prevent GERD (volume reduction techniques) have been previously reported. Gastric intussusception of the distal esophagus was accomplished endoscopically to form an antireflux valve in the pig2Jennings RW Flake AW Muasan G Harrison MR Adzick NS Pellegrini CA A novel endoscopic transgastric fundoplication procedure for gastroesophageal reflux: an initial animal evaluation.J Laparoscopic Surg. 1992; 2: 207-213Crossref PubMed Scopus (9) Google Scholar and Nd/YAG laser application resulted in scar formation of the dog cardia.3McGouran RC Galloway JM A laser-induced scar at the cardia increases the yield pressure of the lower esophageal sphincter.Gastrointest Endosc. 1990; 36: 439-443Abstract Full Text PDF PubMed Scopus (26) Google Scholar Injection of collagen into the lower esophageal sphincter (LES) zone4O'Connor KW Madison SA Smith DJ Ransburg RC Lehman GA An experimental endoscopic technique for reversing gastroesophageal reflux in dogs by injecting inert material in the distal esophagus.Gastrointest Endosc. 1984; 30: 275-280Abstract Full Text PDF PubMed Scopus (49) Google Scholar and sodium morrhuate into the proximal cardia has been performed in the canine model.5Donahue PE Carvalho PF Davis PE Shen YJ Miida I Bombeck CT et al.Endoscopic sclerosis of the gastric cardia for prevention of experimental gastroesophageal reflux.Endosc. 1990; 36: 253-256Scopus (28) Google Scholar Baboons have had gastric fundic sclerotherapy plus a stapling procedure,6Mason RJ Filipi CJ DeMeester TR Peters JH Lund RJ Flake AW et al.A new intraluminal antigastroesophageal reflux procedure in baboons.Gastrointest Endosc. 1997; 45: 283-290Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar and most recently “bulking sutures” have been placed immediately distal to the GEJ using the endoscopic sewing machine7Swain CP Mills TN An endoscopic sewing machine.Gastrointest Endosc. 1986; 32: 36-38Abstract Full Text PDF PubMed Scopus (92) Google Scholar in this model to better define optimal suture placement, number, or configuration of a gastric fold barrier to prevent GERD.8Martinez-Serna T Davis RE Mason R Perciais G Filyer C Lehman G et al.Endoscopic valvuloplasty for GERD.Gastrointest Endosc. 2000; 52: 663-670Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar Humans also have been involved in trials with endoscopic technology to prevent GERD. Collagen injection into the LES zone in 10 patients caused only temporary improvement in symptoms and acid reflux exposure,9O'Connor KW Lehman GA Endoscopic placement of collagen at the lower esophageal sphincter to inhibit gastroesophageal reflux: a pilot study of 10 medically intractable patients.Gastrointest Endosc. 1988; 34: 106-112Abstract Full Text PDF PubMed Scopus (110) Google Scholar and polytetrafluorethylene injections into the LES of 21 patients resulted in only short-term benefits.10Shafik A Intraesophageal polytef injection for the treatment of reflux esophagitis.Surg Endosc. 1996; 10: 529-531Crossref PubMed Scopus (38) Google Scholar However, in a recent preliminary report on the use of the endoscopic sewing machine on a large group of patients over a several-year period of time, there was significant improvement in symptoms and a decrease in duration of acid reflux exposure and use of antireflux medications.11Swain P Park P-O Kjellin T Gong F Kaderkamanathan S Appleyard M Endoscopic gastroplasty for gastro-esophageal reflux disease [abstract].Gastrointest Endosc. 2000; 51: AB14Google Scholar In this issue of Gastrointestinal Endoscopy, 3 investigations are presented concerning the latest results of endoscopic treatment of GERD in the human. A unique spectrum of technology has been adapted to perendoscopic delivery to the esophagus: transmission of radiofrequency energy for localized thermal injury to esophageal tissue,12Triadafilopoulous G DiBaise JK Nostrant TT Stollman NK Anderson PK Edmundowicz SA et al.Radiofrequency energy delivery to the gastroesophageal function for the treatment of gastroesopahgeal reflux disease.Gastrointest Endosc. 2001; 53: 407-415Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar suture plication of proximal fundic folds,13Filipi CJ Lehman G Rothstein RI Raijman I Stiegmann GV Waring JP et al.Transoral flexible endoscopic suturing for treatment of gastroesophageal reflux disease: a multicenter trial.Gastrointest Endosc. 2001; 53: 416-422Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar and implantation of microspheres into the lower sphincteric zone.14Feretis C Benakis P Dimopoulos C Dailianas A Filalithis P Stamou K et al.Endoscopic implantation of Plexiglas (PMMA) microspheres for treatment of GERD.Gastrointest Endosc. 2001; 53: 423-426Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar Is this the future treatment for GERD or are these examples of technology in search of a mission? The studies are interesting but pose significant problems of protocol design and serious questions about each technology, its application, and long-term affects. Unfortunately, none of these studies provided a randomized (sham) control group to validate their unique technologies. This is important in treatment trials involving patients with or without low-grade esophagitis. There can be a surprisingly high placebo response, for example, in studies that use acid suppression medications even when GERD patients have demonstrable esophagitis!15Euler AR Murdock RH Wilson TH Silver MT Parker SE Power L Ranitidine is effective therapy for erosive esophagitis.Am J Gastroenterol. 1993; 88: 520-524PubMed Google Scholar, 16Chiba N DeGara CJ Wilkinson JM Hunt RH Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease; a meta-analysis.Gastroenterology. 1997; 112: 1798-1810Abstract Full Text Full Text PDF PubMed Scopus (793) Google Scholar The GERD patients included in the two larger studies did not have severe erosive esophagitis; the presence of grade III or IV esophagitis or a hiatal hernia larger than 2 cm was criteria for exclusion. In the Triadafilopoulos report, for example, 22 patients (47%) had no detectable esophagitis and 15 patients (32%) had grade I esophagitis—a category debatable for significance of inflammation. Only 11% of patients had a hiatal hernia. In the Filipi study, their 64 patients were “with or without erosive esophagitis, grade 0-2”; no further information was supplied. In the Christos study of 10 patients, 3 patients apparently had grade C esophagitis (LA classification)17Lindell LR Dent J Bennett JR Blum AL Armstrong D Galmiche JP et al.Endoscopic assessment of esophagitis: clinical and functional correlates and further validation of the Los Angeles classification.Gut. 1999; 45: 172-180Crossref PubMed Scopus (1705) Google Scholar and 3 patients had grade B inflammation despite the absence of a significant hiatal hernia in the group. Patients selected for endoscopic therapy in the 3 studies varied in symptomatology and degree of response to medical treatments. In the radiofrequency (RF) trial, the patient group is described by the authors as representing a “heterogeneous spectrum” of clinical disease. These patients had classic heartburn symptoms and/or regurgitation, a daily requirement for antacids (eg., the median dose of proton pump inhibitor [PPI] was 40 mg/day), but “only a partial response” (not quantitated) to medical treatment. Twenty-two patients (49%) took more than a single daily dose of PPI! Patients were scrutinized before and after RF treatment by using the GERD-Health Related Quality of Life questionnaire (GERD-HROL). Medical outcomes study (SF-36) was completed while both on and off medications and at the end of the treatment trial. The 24-hour ambulatory pH monitoring test was also obtained before and after treatment (while off medication). The mean duration of acid exposure before entering the RF study on 24-hour pH monitoring was elevated (11.7%) and occurred more frequently with patients in the upright position. Interestingly, among the other symptoms recorded for the RF patients at baseline were dysphagia (cause?) 30% and flatulence 81%. Patients enlisted into the endoscopic suturing protocol were less well defined and appear to have marginal GERD problems, that is, the presence of 3 or more heartburn episodes per week (off medication), “dependence” on antisecretory medications, and documented acid reflux by 24-hour ambulatory pH measurement (>4% duration of acid exposure) were sufficient criteria for selection. Patients with dysphagia or obesity were excluded from the study. The patients who underwent endoscopic implantation of microspheres into the LES zone were deemed “medically intractable” according to the author. Apparently, the patients did not respond to a mixture of medical therapy (exactly what medications, dosage, or duration is not detailed) or “relapsed” more than 3 times after successful medical treatment within 1 year. Radiofrequency energy has been used extensively in medicine to alter tissue for various purposes, for example, heating myocardial tissue to create a lesion that interrupts conduction through a portion of the reentry circuit in patients with cardiac arrhythmias18Morady E Radiofrequency ablation as treatment for cardiac arrhythmias.New Engl J Med. 1999; 340: 534-544Crossref PubMed Scopus (244) Google Scholar or destroying unresectable primary or metastatic hepatic malignancies.19Curley SA Izzo F Delrio P Ellis LM Granchi J Vallone P et al.Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients.Ann Surg. 1999; 230: 1-8Crossref PubMed Scopus (1018) Google Scholar Recently, temperature-controlled RF delivery to the GEJ has been reported to reduce the frequency of transient lower esophageal sphincter relaxations (TLESRs) by almost 50% in the canine20Kim MS Dent J Holloway R Utley DS Radiofrequency energy delivery to the gastric cardia inhibits triggering of transient lower esophageal sphincter relaxation in a canine model [abstract].Gastroenterology. 2000; 118: A860Abstract Full Text PDF Google Scholar and human.21Dibaise JK Akromis I Quigley EM Efficacy of radiofrequency energy delivery to the lower esophageal sphincter in the treatment of GERD [abstract].Gastrointest Endosc. 2000; 51: AB896Google Scholar The exact mechanism of action is unknown, but the effect may be caused by ablation of nerve pathways responsible for TLESRs or may be a tissue “tightening” effect caused by heat-induced collagen contraction. (The latter has been reported in RF therapy of joint problems.) However, manometrically defined LES length and function are not altered by RF treatment. Despite the accompanying schematic drawing suggesting “thickening” at the GEJ after treatment, EUS evaluation of tissue depth of this esophageal zone was not part of the protocol. After identifying the squamo-columnar junction (SCJ) endoscopically, the 30F RF catheter (Curon Medical Inc., Sunnyvale, Calif.) is inserted on a nonvisualizing balloon probe. RF energy (temperature 85°) is applied through 4 stiletto-like 5.5 mm electrodes into the esophageal wall at multiple sites from 2 cm below to 2 cm above the SCJ for 2-minute intervals with the balloon inflated. The mucosa is cooled with water irrigation during RF thermal induction to prevent surface injury. (The instrument was deployed a mean of 13.8 “sets” in this report.) RF delivery time averaged 52 minutes, whereas total procedure time was 69 minutes. The investigator's systematic study reviewed and quantitated the results of RF therapy on GERD symptoms, acid exposure, quality of life scores, and inflammatory changes. There were significant improvements at 6 months follow-up in GERD scores (26 to 7) mental and physical SF-36 scores (46 to 56 and 41 to 52, respectively), acid exposure time (11.7%-4.8%), and esophagitis (11 of 15 grade I patients improved and 8 of 10 grade II patients improved). Importantly, 87% of patients no longer required medication. Although only 3 complications (self-limited) were reported in this multicenter series, the RF technique has potential problems and inherent dangers. The technique requires considerable time, frequent deploying of the sharp prongs, and balloon inflations. The esophagus is not static; it shortens 1 to 2 cm with deglutition or respiration. Multiple opportunities for esophageal laceration or perforation are presented during the procedure. Retching could be particularly dangerous, either while the instrument is impacted (within the wall) or is being deployed. Significant analgesia/sedation may be required during this time, especially if pain is experienced by the patient because of RF heat. Further concerns arise about potential long-term effects of RF on esophageal function. Does tissue “tightening” 2° to RF treatment eventually cause distal esophageal noncompliance—and possibly dysphagia for solids? However, the frequency of dysphagia decreased from a baseline value of 30% to a 6-month value of 2% in this study. Does RF treatment impair or ablate sensory receptors so that future GERD episodes may no longer be associated with the warning signals of heartburn and thus escape patient awareness? (Mean heartburn scores were “improved” at 6 months.) Finally, if TLESRs are significantly decreased, will belching be impaired or prevented? Will a gas/bloat syndrome become a problem? (Flatulence/bloating decreased from 83% to 34% at 6 months; eructation was not evaluated.) Endoscopic gastroplasty with the suturing device (Bard Interventional Endoscopic Suturing System; Billerica, Mass.) for GERD treatment is a more complex and demanding technique. The procedure requires placement of an oropharyngeal tube and requires 8 steps (count them) per plication. If a second or third gastric fold plication is performed, the above steps are repeated. Procedure time is extensive (mean time 68 minutes) and apparently requires more than the standard conscious sedation in a significant minority of patients (14% of patients had “monitored” anesthesia; 17% of patients had general anesthesia.) Ten of the 64 patients withdrew from the study before the 6-month follow-up. The procedure was completed in 1 day in 60 patients but required “more than 1 day” in 4 patients. A repeat procedure was apparently required in 11 patients (reason?) sometime after the first month. Heartburn severity frequency and regurgitation improved in this patient group at mean follow-up of 6 months after endoscopic gastroplasty. Twenty-four-hour pH monitoring showed improvement in percentage of total time pH <4.0 at 6 months. Sixty-two percent of patients were taking less than 4 doses of medication per month. There was no postplication dysphagia reported. The investigators theorize that the effectiveness of endoscopic gastroplasty may result from lesser gastric curvature plication buffering the muscularis of the LES zone and altering the anatomy to prevent TLESRs. (Neither linear nor circumferential plication configuration affected the study results.) To accomplish this goal, sutures need to be accurately placed. In this study, however, the “intended” suture location was accomplished in only 81% of plications. The efficacy of fundic plication is extremely “operator dependent.” The investigators discuss this situation, noting that accuracy and placement of plication stitches “was a challenge and highly dependent upon each investigator team in the multicenter study completing pre-study animal training” and appreciating “limited” visualization of stitch placement. Training experience ranged from 4 to 15 animals per physician. The adverse events associated with this procedure were not “device related,” but this was a significant associated morbidity including one case of suture perforation! Before acquiring this device, the manufacturers require each operator to obtain experience with the procedure in the animal laboratory. Endoscopic implantation of Plexiglas microspheres (bolstering the LES zone) by endoscopic injection to prevent GERD is a less demanding technical procedure. The authors averaged 20 minutes per procedure and a volume implant of 31.7 mL (range 24 to 39 mL). The volume per injection and the number of injection sites are not specified. For some reason, a sigmoidoscope was used (perhaps to accommodate the short [90 cm] catheter, which reduces flow resistance). A “high pressure capability” syringe was used but not described. Polymethylmethylacrylate (PMMA) 100 μm microspheres dispersed in gelatin solution (Rofi Medical Int., Breda, the Netherlands) was used as the bulking agent to “support” the LES zone. The small-sized spheres are thought to hinder phagocytosis and dislocation-migration away from the implantation site, which has been a problem in the past with this technique.9O'Connor KW Lehman GA Endoscopic placement of collagen at the lower esophageal sphincter to inhibit gastroesophageal reflux: a pilot study of 10 medically intractable patients.Gastrointest Endosc. 1988; 34: 106-112Abstract Full Text PDF PubMed Scopus (110) Google Scholar EUS performed immediately postprocedure and at 6 months showed “continuing presence” of PMMA at the injection sites, but this was strictly a qualified judgment. The results of bolstering the LES showed improvements in a number of GERD features in 9 of 10 patients, although quantification was not nearly as rigorous as that reported in the other two studies. For example, antireflux medication was reduced but not itemized. However, the elevated mean values obtained for the ambulatory pH study before implantation (24.5%) were reduced after injection therapy (7.2%) and the grade of esophagitis improved in 4 of 5 patients. Unfortunately, the precise time of posttreatment follow-up is extremely vague. The latest medical technologic developments can sometimes be approved for patient consumption before thorough validation of therapeutic benefit (or risks). Witness the Garron gastric balloon for treating obesity.22Mathus-Vliegen E Tytgat G Veldhuyzen-Offermans E Intragastric balloon in the treatment of super-morbid obesity. Double-blind, sham-controlled, crossover evaluation of 500 milliliter balloon.Gastroenterology. 1990; 99: 362-369Abstract PubMed Google Scholar It was a bust! Physicians at times are overeager in introducing the “newest” technology into their practices to provide better patient care. Often, this haste obviates appropriate training and experience as was noted with the introduction of the laparoscopic cholecystectomy procedure. Almost overnight, many U.S. surgeons developed these skills after a brief experience with several porcine models.23National Institutes of Health Consensus Development Conference statement on gallstones and laparoscopic cholecystectomy.Am J Surg. 1993; 165: 390-396Abstract Full Text PDF PubMed Google Scholar Is there a need for any of these endoscopic treatments in the majority of this patient group? A partial response to medical therapy suggests conducting a further trial of titrating medication to a higher dosage or substituting a different class of antacid drugs. Perhaps dyspepsia may be a major component of the GERD symptoms in some of these patients based on partial response to medical therapy.24Ritter MP Peters JH DeMeester TR Crookis PF Mason RJ Green I et al.Outcome after laparoscopic fundoplication is not dependent on structurally defective lower esophageal sphincter.J Gastrointest Surg. 1998; 2: 1567-1572Crossref Scopus (28) Google Scholar The majority of patients included in these 3 studies would not be referred by gastroenterologists for an operative fundoplication because they lack the features usually associated with severe GERD, for example, esophagitis greater than grade II, and hiatal hernia greater than 2.0 cm. These endoscopic therapies apparently are not currently suited for patients with severe GERD who would most benefit from conservative treatment. The hypothesis for the use of the endoscopic suturing trial, for example, was an expectation that “initial procedures should be half as effective as the well-established Nissen fundoplication.” These are not lofty expectations, especially in light of the morbidity reported with the initial trial results. Unfortunately, the problem has begun already. Two of the endoscopic treatment modalities for GERD are being openly promoted to physicians by vendors providing instrumentation or short-term tuition training courses involving animal models. These procedures are operator-dependent and require experienced, adroit endoscopists. The multicenter involvement in the endoscopic suturing study reflects this problem. Both of these studies are supported by industrial grants from respective vendors who are already distributing these devices to endoscopists. The public has become aware of nonsurgical GERD treatments and at least one major clinic has advertised the availability of gastric plication “as an outpatient procedure with results comparable to those achieved with laparoscopic surgery.”25Mayo Clinic Clinical trends in the practice of Medicine.in: Endoscopic fundoplication for gastroesophageal reflux disease. 16. Mayo Clinic Update, 2000: 1-3Google Scholar Before these endoscopic procedures for GERD become widely available to consumers there is a critical need for placebo-controlled studies and follow-up of outcomes longer than 6 months.26Lehman G Endoscopic and endoluminal techniques for the control of gastroesphageal reflux: are they ready for widespread clinical application?.Gastrointest Endosc. 2000; 52: 808-811Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar Until this information is available, there should be a moratorium on the general use of the endoscopic treatments of GERD in patients who, for the most part, have mild disease or who do not wish to take medication. Endoscopists have been critical of the problems associated with fundoplication surgery as “first line” therapy for GERD patients with symptom profiles similar to those involved in these 3 studies.27Hogan WJ Shaker R Life after antireflux surgery.Am J Med. 2000; 108: 181S-191SAbstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 28Johnson DA Younes Z Hogan WJ Endoscopic assessment of hiatal hernia repair.Gastrointest Endosc. 2000; 52: 650-659Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar The same accusations can be leveled at endoscopic therapy for GERD until further information is accrued concerning efficacy and risks. There may be a definitive role in the future for this endoscopic technology in the schema of GERD treatment. Unless the efficacy of these endoscopic procedures is scientifically validated by appropriately designed protocols and outcome studies, the GI community may once again see another technologic bust! Radiofrequency energy delivery to the gastroesophageal junction for the treatment of GERDGastrointestinal EndoscopyVol. 53Issue 4PreviewBackground: In this multi-center study, the feasibility, safety, and efficacy of radiofrequency (RF) energy delivery to the gastroesophageal junction (GEJ) for the treatment of gastroesophageal reflux disease (GERD) were investigated. Methods: Forty-seven patients with classic symptoms of GERD (heartburn and/or regurgitation), a daily anti-secretory medication requirement, and at least partial symptom response to drugs were enrolled. All patients had pathologic esophageal acid exposure by 24-hour pH study, a 2 cm or smaller hiatal hernia, grade 2 or less esophagitis, and no significant dysmotility or dysphagia. Full-Text PDF Transoral, flexible endoscopic suturing for treatment of GERD: A multicenter trialGastrointestinal EndoscopyVol. 53Issue 4PreviewBackground: A totally transoral outpatient procedure for the treatment of GERD would be appealing. Methods: A multicenter trial was initiated that included 64 patients with GERD treated with an endoscopic suturing device. Inclusion criteria were 3 or more heartburn episodes per week while not taking medication, dependency on antisecretory medicine, and documented acid reflux by pH monitoring. Exclusion criteria were dysphagia, grade 3 or 4 esophagitis, obesity, and hiatus hernia greater than 2 cm in length. Full-Text PDF Endoscopic implantation of Plexiglas (PMMA) microspheres for the treatment of GERDGastrointestinal EndoscopyVol. 53Issue 4PreviewBackground: A gelatinous implant containing polymethylmethacrylate (PMMA) beads is successfully used to augment the diminished thickness of the chorium in patients with skin defects and wrinkles. The aim of the present study was to determine whether submucosal injection of PMMA microspheres into the lower esophageal folds decreases the severity of symptoms and acid reflux in patients with GERD. Methods: Endoscopic submucosal implantation of PMMA was carried out in 10 patients with GERD who were either refractory to or dependent on proton pump inhibitors. Full-Text PDF
Referência(s)