THE WORD ON GERD
From the 5th Annual Creighton University Medical Center Esophageal Conference
| MEDICAL THERAPY FOR GASTROESOPHAGEAL REFLUX DISEASE (GERD)—Peter J. Kahrilas, MD, Gilbert H
Marquardt Professor of Medicine, Division of Gastroenterology, Department of Medicine, Northwestern University Feinberg
School of Medicine, Chicago, IL
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Esophageal Disease
| Erosive esophagitis: treatment focuses on improving rates of tissue healing; data show—antacids relatively ineffective
(placebo response ≈20%; therapeutic gain ≈10%); H2 -receptor antagonists (H2 RA; therapeutic gain ≈20% regardless of
disease severity); proton pump inhibitors (PPIs; achieve best healing rates [up to 95%]); AZD0865—experimental drug;
new class of acid inhibitors; more potent acid inhibitor than esomeprazole 40 mg, but did not enhance clinical efficacy
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 | Clinical efficacy and ceiling effect: once acid-inhibition ceiling reached, additional increases in dosing do not provide
added benefit; esomeprazole vs lansoprazole for managing heartburn associated with esophagitis—equally effective;
results suggestive of therapeutic ceiling
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| Nonerosive reflux disease (NERD): PPIs—achieve ≈25% therapeutic gain, compared to placebo (response does
not increase with dose); reduce acid secretions, ie, therapeutic response varies directly with acid exposure; conceptual
subgroups include patients with—treated esophagitis; NERD as originally conceived (ie, naive to treatment but without
erosive esophagitis); volume reflux (symptoms presumably caused by reflux volume, not excessive acid; patients
generally show partial response to PPIs, ie, burning will resolve, chest pain and regurgitation will not); hypersensitivity;
not acid reflux disease (NARD; includes patients with functional heartburn or unrelated disease processes that have been
diagnosed as reflux based on limited evidence); establish correlation between reflux and symptoms by using—pH
monitoring to evaluate patients not on PPI therapy; impedance monitoring to evaluate patients treated with PPIs;
pathophysiology—symptoms develop when reflux stimulates chemoreceptors in esophagus and produces mechanostimulation
by distending esophagus; heartburn occurs mainly in response to chemostimulation (element of mechanostimulation
exists); regurgitation or chest pain produced by balanced input from chemostimulation and mechanostimulation;
cough caused predominantly by mechanostimulation
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Extraesophageal Syndromes
| Observations drawn from study data: established extraesophageal syndromes include cough, laryngitis, and
asthma; vocal fold erythema relatively specific for abnormal condition; many findings (eg, arytenoid erythema, interarytenoid
bars, and cobblestoning) also detected in many patients without reflux disease; response to treatment—study
showed no difference between response rates with esomeprazole or placebo among patients with reflux laryngitis (individuals
with dominant esophageal symptomatology excluded); those without heartburn did not respond to PPI therapy;
conclusion—in absence of heartburn or regurgitation, unexplained asthma and laryngitis probably unrelated to GERD
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| Risk management in GERD: esophageal adenocarcinoma—rare; existing treatment options do not decrease risk;
cases rarely develop via sequential progression from symptomatic problem to esophagitis, Barrett’s esophagitis, and
cancer; focus should be on balancing incremental risk of GERD treatment against benefit derived from controlling
manifestations of GERD, not on preventing cancer
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| Risks associated with chronic PPI therapy (as evaluated by Food and Drug Administration Gastrointestinal Advisory
Panel): hypergastrinemia and increased risk for cancer (species-specific to laboratory rats; problem does not occur
in humans); accelerated progression of Helicobacter pylori gastritis to intestinal metaplasia and gastric cancer
(PPIs increase corpus inflammation in presence of H. pylori infection; because H pylori infections have not been
associated with increased risk for atrophic gastritis, evaluation for H pylori not recommended for patients undergoing
PPI therapy); achlorhydria and increased risk for cancer (achlorhydria promotes growth of bacteria that convert
nitrates to carcinogenic N-nitrosamine; link between PPI use, increased levels of gastric N-nitrosamine, and
cancer remains speculative); achlorhydria and enteric infections (achlorhydria disables gastric barrier to ingested
pathogens; occasional cases of enteric infection reported among patients taking PPIs; PPI use considered independent
risk factor for Clostridium difficile diarrhea in patients taking antibiotics); community-acquired pneumonia
(presumably, gastric colonization associated with achlorhydria can increase risk for aspiration pneumonia; but,
people who take PPIs also more likely to drink alcohol, smoke tobacco, be obese, and have GERD; small effect remains
once confounding factors controlled); malabsorption of fat, minerals, and vitamins (concern existed that PPI
use would compromise absorptive processes requiring acid; in fact, effect of PPIs on absorption of fat, calcium,
iron, and B12 considered trivial); calcium malabsorption (concern about correlation between prolonged use of
PPIs, calcium malabsorption, and increased risk for hip fracture; limited data suggest association increases with
duration of PPI therapy); drug-drug interactions (clinically significant interactions rare); pregnancy (omeprazole category
C drug [other PPIs category B]; data show PPIs do not present major teratogenic risk); acute interstitial nephritis
(side effect associated with drug class; risk ≈1 in 12500 patients)
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| Conclusions: PPIs safe; chronic use associated with slight risk for enteric infection and interaction with warfarin; overuse
remains main concern
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| SURGICAL THERAPY FOR GERD—Jeffrey H. Peters, MD, Seymour I. Schwartz Professor, and Chair, Department of
Surgery, University of Rochester School of Medicine and Dentistry, Rochester, NY
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| Fundoplication: most surgical candidates have undergone trial with PPI and have acid-related symptoms, volume-related
symptoms, or symptoms unrelated to GERD; predictors of successful surgical outcome include positive pH study
(most important factor), types of symptoms, and response to other therapy; some factors previously thought to significantly
affect outcome of antireflux surgery (eg, incompetent lower esophageal sphincter) now considered less important;
many factors involved in pathophysiology of reflux disease
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| Nissen fundoplication: gold standard; more effective than partial fundoplication and Collis gastroplasty; does not require
individual modifications for patients who have been diagnosed with GERD, ie, approach can be performed on most
patients regardless of underlying physiology
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| Symptom assessment: key; surgeon must understand symptoms before operating for GERD; characterization of type
and degree of symptoms critical to treatment outcome; typical symptoms include heartburn, regurgitation, and dysphasia;
outcomes less predictable in patients with atypical symptoms
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| Patient evaluation: problem—each symptom responds differently to surgery; most patients with GERD present with
multiple symptoms of gastrointestinal (GI) disease; some symptoms (eg, irritable bowel symptoms) unrelated to reflux
and will remain after antireflux procedure; let patient know—antireflux procedures stop reflux and improve symptoms
caused by reflux, but symptoms not related to reflux likely will not improve; factors associated with poor surgical
outcomes—strictured and shortened esophagus; severe motility disorders; intrathoracic stomach; severe gastric abnormalities;
history of failed repair
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| Issues with Nissen fundoplication: approach becoming standardized; correlating relief of specific symptoms to particular
aspect of surgical procedure can be challenging research effort (eg, mobilization of fundus probably reduces incidence
of dysphagia); technical problems associated with ≈15% surgical failure rate include—inadequate or absent
crural repair; failure to perform short gastric division, lengthening shortened esophagus, or carrying out sac excision during
repair of large paraesophageal hernia; hiatal hernia—present in most patients who undergo antireflux surgery; repair
remains key component of successful surgery; failure to repair hernia may result in adverse effects (eg, some
postoperative dysphagia and hiatal problems traceable to diaphragm, not fundoplication); keys to successful surgery—
be as certain as possible that reflux is source of patient’s symptoms; identify symptoms related to factors other than
GERD; make sure patient has realistic expectations about which factors surgery will address; carefully perform standardized
technique in patients with severe disease or complex anatomy and physiology; note—when fundoplication does not
resolve symptoms related to distention, use imaging and pH studies to show patient reflux has been eliminated
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| Altered physiology after fundoplication: Nissen fundopli-cation—stops reflux; achieves durable results; helps
normalize function of gastroesophageal junction (GEJ), ie, resistance and flow characteristics improve; changes in resistance
and postoperative side effects—dysphagia associated with postoperative delay in transit times of liquids
and solids in esophagus and around GEJ; altered physiologic function of wraps also may cause obstruction
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| Gastric physiology: patients with reflux have subtle abnormality in stomach function (ie, when patient eats, gastric fundus
distends more and corrects less than in patients without reflux); fundoplication restores gastric function to better
than normal (observation provides physiologic correlate to increased gastric emptying and early postoperative diarrhea)
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| Current data suggest fundoplication: achieves good results; should be considered for managing individuals with
severe GERD; probably underutilized
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| ENDOSCOPIC THERAPY FOR GERD: PRESENT AND FUTURE —Richard I. Rothstein, MD, Professor of Medicine,
Dartmouth Medical School, Hanover, and Chief, Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical
Center, Lebanon, NH
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| Endoscopic options: categories—plication or sewing techniques; radiofrequency thermal treatment to GEJ; injectable
or implantable biopolymers; effects—alter tone, length, or frequency of transient relaxations of lower esophageal
sphincter (LES); change cardia (compliance or anatomy); provide mechanical obstructors to refluxate
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| Devices in use: EndoCinch (CR Bard)—requires 2 videoendoscopes (one attaches to EndoCinch capsule; one used to
perform cinching); achieves mucosa-to-mucosa apposition; typically places 2 to 4 pleats; sham-controlled data suggest
no effect of EndoCinch proved superior to sham; ability of device to provide durable results questionable; associated
with fewer complications than any other device evaluated (include vomiting, transient dysphagia, and oxygen desaturation
during procedure); Plicator (NDO)—surgeon passes low-profile 5.9-mm pediatric gastroscope through device;
serosa-to-serosa apposition achieved (associated with better results than EndoCinch); 50% of patients in treated group
experienced improvement in GERD Health-Related Quality of Life (HRQL) scores (vs 20% of patients in sham
group); 50% of treated patients no longer required PPIs (vs 23% of controls); treatment associated with improved pH;
5-yr data suggest durable results; current design and surgeon education has reduced complications associated with first
version of instrument
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| Stretta device (CSM): delivers radiofrequency energy to GEJ; expensive; improved heartburn, heartburn scores, and SF
36 quality of life scores; at ≈ 6 mo—collagen deposition takes place; changes in compliance and activity occur; overall
percentage of time when pH was <4 and percentage of patients able to discontinue daily medications were similar in
both sham and treatment groups; additional points—long-term data suggest device achieved better results than previous
treatment used by patient; proper surgeon education eliminated procedure-related mortality
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| Devices no longer used: Wilson-Cook endoscopic suturing device (data insufficient to justify use); Enteryx biopolymer
(Boston Scientific)—injected with Gatekeeper (Medtronic) hydrogel implants; withdrawn because of complications
associated with inaccurate injection of material; Gatekeeper system—not sufficiently robust to change parameters
of lower esophageal sphincter (LES) length; did not change pH profiles or eliminate esophagitis and other symptoms; implanted
devices relatively inert and should probably be left in place (ie, procedure to remove device relatively simple, but
is associated with high risk for hemorrhaging and perforation)
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| Devices under evaluation: Olympus suction device—suctions tissue in and fires T-tag-like pledgeted devices; modest
level of efficacy suggested in one study; Syntheon Anti-Reflux Device (ARD)—placed with individualized catheter;
can be used with any gastroscope; profoundly changes cardia; trial data insufficiently robust to demonstrate superiority
over other options; utility of device not maximized; EsophyX (EndoGastric Solutions)—available in Europe, but not in
United States; achieved profound remolding; early results less promising than had been hoped; SafeStitch—tries to address
shortcomings of previous endoscopic therapies; draws mucosa and submucosa into window where it can be held in
place, injected, stripped of mucosa, and stitches placed in one passage
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| Future developments: new devices—Boston Scientific direct-drive system (used on standard endoscope to provide
accessories with multiple ranges of motion); EndoVia device (computer-designed robotic unit that can manipulate instruments);
USGI Medical TransPort unit; surgeons will—achieve access through stomach, colon, and vascular walls;
learn to use new procedures (eg, transgastric and transvaginal colocystectomies; T tag delivery, crural closure, and
mesh placement performed through natural orifices); use new tools (eg, Eagle Claw suturing device; T-tag backloaded
in hollow needle that can revolutionize intra- and extraluminal laparoscopic surgery)
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| Additional observations about endoscopic surgery: ideal candidates have—classic symptoms; nonerosive disease;
ability to respond well to acid suppression and conventional surgery; poor candidates do not—respond well to
acid suppression; have proven reflux disease; less important issues include—short segment metaplasia; manometry
profile; predictors of better response include—LES pressure; typical symptomatology; response to acid suppression;
additional uses to investigate include—managing supraesophageal reflux disease, children, pregnant women, patients
who have undergone bariatric surgery (ie, small stomach leaves little area to work in and creates difficulties when redoing
surgery); altering reflux volume; providing alternative following failed laparoscopic Nissen surgery
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| Endoscopic options: can provide symptom relief and reduce use of GERD medication (sham options have demonstrated
similar efficacy); has not demonstrated ability to heal esophagitis (potential value may depend on more experience
and better technique); will provide durable effect if technique can be optimized; requires better tools and techniques
to improve ability to normalize pH; points—necessity of normalizing pH (combination of volume reduction and PPI
therapy may be sufficient to make people feel better); accuracy of pH monitoring in assessing patient status (impedance
may be more accurate assessment tool); ability of endoscopic GERD surgery to survive (endoscopic technology can play
role in managing reflux disease, but research must continue to find appropriate endoscopic techniques)
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Suggested Reading
Fennerty MB et al: Efficacy of esomeprazole 40 mg vs. lansoprazole 30 mg for healing moderate to severe erosive
esophagitis. Aliment Pharmacol Ther 21:455, 2005; Filipi CJ et al: Endoscopic antireflux repairs. Minerva Gastroenterol
Dietol 53:189, 2007; Håkanson BS et al: Open vs laparoscopic partial posterior fundoplication. A prospective
randomized trial. Surg Endosc 21:289, 2007; Kahrilas PJ Lee TJ: Pathophysiology of gastroesophageal reflux disease.
Thorac Surg Clin 15:323, 2005; Kahrilas PJ et al: A randomized, comparative study of three doses of AZD0865
and esomeprazole for healing of reflux esophagitis. Clin Gastroenterol Hepatol; 2007; Peters JH: The importance of
symptom assessment in the surgical treatment of gastroesophageal reflux disease and Barrett’s esophagus. Surg Endosc
20Suppl 2:S456, 2006; Robertson DJ et al: Proton pump inhibitor use and risk of colorectal cancer: a population-based,
case-control study. Gastroenterology 133:755, 2007; Rothstein RI, Dukowicz AC: Endoscopic therapy for gastroesophageal
reflux disease. Surg Clin North Am 85:949, 2005; Rothstein RI, Filipi CJ: Endoscopic suturing for gastroesophageal
reflux disease: clinical outcome with the Bard EndoCinch. Gastrointest Endosc Clin N Am 13:89, 2003;
Salminen PT et al: Comparison of long-term outcome of laparoscopic and conventional Nissen fundoplication: a prospective
randomized study with an 11-year follow up. Ann Surg 246:201, 2007.
Educational Objectives
| The goal of this program is to improve the management of gastroesophageal reflux disease (GERD). After hearing
and assimilating this program, the clinician will be better able to:
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| 1. Discuss current data on the medical management of esophageal and extraesophageal syndromes associated
with GERD.
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| 2. Assess benefits and potential risks of proton pump inhibitor therapy for GERD.
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| 3. Define the role of Nissen fundoplication in the management of GERD.
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| 4. Review key concepts for performing successful Nissen fundoplication.
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| 5. Describe the past, present, and future of endoscopic surgical technology for managing GERD.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose relevant
financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified
conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business
or commercial interest. For this program, the following has been disclosed: Dr. Kahrilas is affiliated with AstraZeneca; Dr.
Rothstein is affiliated with Bard, BARRX Medical, Boston Scientific, Ethicon, NDO, Olympus, and SafeStitch LLC.
Acknowledgments
Drs. Kahrilas, Peters, and Rothstein gave their scientific presentations at the 5th Annual Creighton University School of
Medicine Esophageal Conference held September 6-7, 2007, in Omaha, NE. The Audio-Digest Foundation thanks the
speakers and Creighton University School of Medicine for their cooperation in the production of this program.
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