Patient Information
1. What is GERD?
Gastroesophageal Reflux Disease (GERD) is the reflux of gastric contents back into the esophagus frequently enough to disrupt your quality of life. GERD occurs when the sling musculature of the GastroEsophageal Junction (GEJ) becomes stretched and loose, and the Angle of His is lost. The Angle of His is the angle at which the base of the esophagus enters the stomach.
In a healthy individual, the tissue at the base of the esophagus doubles back as it enters the stomach, creating a double-layer of tissue that serves as a valve by resting against the lesser curve of the stomach. This valve opens during swallowing and then remains closed to prevent reflux of gastric contents into the esophagus. Reflux of gastric acid, pepsin and other enzymes and caustic agents irritate the squamous epithelium of the esophagus, and may lead to erosion and ulceration of esophageal mucosa.
Eventually, in a subset of about 10% of the refluxing population, the squamous epithelium may be progressively replaced by a columnar or intestinal epithelium. The presence of this columnar or intestinal epithelium in the esophagus is a premalignant condition named Barrett's Esophagus (BE), and yields a ~10% risk of progression to adenocarcinoma of the esophagus, which is much higher than the risk of the general population.
2. What causes GERD?
GERD is caused by a failure of the antireflux barrier (ARB) and its primary component, the GastroEsophageal valve (GEV). The understanding of the GEV has continued to progress in recent years, and more focus is currently being placed on the GEV, rather than the lower esophageal sphincter (LES) as the largest contributor to the ARB. In healthy patients, the Angle of His, the angle at which the esophagus enters the stomach, is intact creating a valve that prevents duodenal bile, enzymes, and stomach acid from traveling back into the esophagus where it can cause burning and inflammation of the sensitive esophageal tissue.
Previous endoluminal treatments focused predominantly on the LES. However, failure to effectively treat reflux long-term with endoluminal therapies which focused only on the LES combined with the fact that surgical approaches like Nissen fundoplication recreate the GEV and have excellent long-term efficacy, has led to an awareness that the GEV is probably the most powerful component of the ARB.
Researchers have demonstrated the robust nature of the GEV and have shown that the intact GEV alone is highly competent to stop reflux. For example, in cadavers, where no muscle tone or LES pressure is present, the stomach ruptured when filled with water before reflux would occur.[1] This displays the power of the GEV to stop reflux even in the absence of any LES pressure.
Proper function of the ARB to prevent reflux is dependent upon the geometry of the GEV. In healthy patients, the base of the esophagus extends into the stomach such that the Angle of His is maintained, and a 180-270 degree musculo-mucosal ridge is present. This ridge normally rests closed against the lesser curve of the stomach to prevent reflux of the stomach contents.
When the cardia sling musculature becomes stretched or attenuated, the Angle of His deteriorates into a funnel shaped GEJ and the GEV is lost. Loss of the GEV, with or without hiatal hernia, dilation of the stomach, or a consistent increase in intraabdominal pressure, such as with pregnancy or morbid obesity, can lead to reduced resistance to reflux. Consequently, one of the major tenants of antireflux surgery is to restore normal geometry to the GEJ anatomy.
Endoluminal fundoplication (ELF) procedures performed using the EsophyXTM device restore the geometry of the GEJ and recreate the natural, unidirectional valve mechanism necessary to stop GERD. The presence of hiatal hernia can also cause increased acid exposure of the esophagus and is generally correlated with more severe GERD symptoms. Hiatal hernias reduce the efficiency of esophageal contraction due to a loss of anchoring, and an acid space often develops above the diaphragm, which increases the likelihood of reflux by allowing gastric juices to be swept into the lower esophagus. In this case, a GEV is usually not present any longer or is highly insufficient (Hill Grade III or IV).
 
Hill Grade III, IV
3. What are the consequences of GERD?
In severe or chronic GERD, regurgitation occurs regularly, spilling acid, bile, and other stomach contents not only into the esophagus but also into the lungs, mouth, pharynx and/or nose. Thus, GERD can lead to a variety of complications including esophagitis, anemia, peptic stenosis, Barrett's esophagus, cough, asthma, recurrent bronchitis, ENT manifestations and sleep disturbance, and in the worst case, even esophageal adenocarcinoma.
‘Atypical' symptoms associated with GERD can include sore throat, cough, laryngitis, dental erosions, discomfort in the ears and nose, and asthma like symptoms caused by the aspiration of stomach contents into the lungs. These atypical symptoms are typically not resolved through drug treatment alone and require reflux cessation to prevent reoccurrence and progression.
The complications associated with untreated GERD are well documented and can have a significant impact on the quality of life and, in extreme cases, life expectancy. During the early stages of GERD, patients often feel a burning sensation in their chest typically referred to as heartburn. As the disease progresses, the normal anatomy of the GEJ can change reducing the capacity of the ARB to prevent acid from refluxing into the esophagus. When the caustic gastric contents enter the esophagus they damages the esophageal tissue and causes inflammation known as esophagitis. Esophagitis can quickly become a chronic condition and, if the damage is severe, esophageal ulcers can form.
Esophageal ulcers can cause bleeding, sometimes severe, and discomfort which can result in esophageal scaring. This scar tissue forms on the inside of the esophagus and can result in strictures, or narrowing, of the esophagus. Strictures can make it difficult and painful to swallow and often require endoscopic or surgical intervention in the form of dilatations or surgical widening (myotomy) to restore the normal esophageal passage. In addition, reflux must be stopped in order to prevent strictures from reoccurring.
The impact of GERD on the esophageal mucosa depends on various factors including the number of reflux episodes, duration of contact, pepsin, and acid content of the gastric fluid, and esophageal peristalsis. If GERD is left untreated, the cells that line the esophagus can begin to change and become similar to the cells of the stomach or intestine. This condition is known as Barrett's Esophagus.
Although it may be present in the absence of GERD, BE can be a severe complication of GERD and, once manifested, can cause malignant degeneration which increases the risk of progression to esophageal adenocarcinoma 30 to 125 times.[2] Because Barrett's esophagus is a pre-cancerous condition, it requires regular endoscopic examinations and biopsies to monitor the progression of the disease.
When progression from Barrett's esophagus to adenocarcinoma occurs, the onset is typically rapid and, once manifested, is difficult to treat. Since pharmacological treatment does not stop reflux, including highly caustic duodenal reflux, it also does not prevent progression to GERD related BE.[3] Therefore, patients should seek a medical evaluation as soon as GERD symptoms appear and should continue treatment and surveillance as prescribed by a physician.
4. What is the socio-economic impact of GERD?
While GERD is rarely a life threatening disease it does have far reaching impacts on both suffers as well as their family, friends, employers, and many others. Because GERD is a chronic disease, both the direct and indirect costs are often quite high. Until recently, the most common treatment option, drug therapy, involves a daily regime of pharmaceutical(s), regular examinations, dietary restrictions, and other significant lifestyle modifications.
The direct and indirect costs of this approach are significant on both a micro- and macroeconomic level. The American Gastroenterological Association estimates the direct costs of GERD to be $9.8 Billion per year in the
US alone. The indirect costs, while much more difficult to quantify, are estimated at $13.8 Billion per year.[4] Because of the chronic nature of the disease and the fact that the pharmaceutical approach requires frequent treatment, medication makes up 64% of the total cost burden, followed by hospitalization at 19%, doctor visits at 7%, and days off work 10%.[5]
From a microeconomic perspective GERD is estimated to cost $3,441 per patient/employee per year including both direct and indirect costs. This includes time away from work, loss of productivity, and hard costs associated with the treatment of the disease itself.[6] These costs demonstrate a significant burden on individuals and employers. When GERD is treated through a pharmaceutical approach these burdens are typically lifelong.
From a quality of life perspective, GERD sufferers who qualify for and elect a laparoscopic Nissen fundoplication (LNF) procedure often score at or near as well as non-GERD sufferers in human-quality of life (HRQL) indices seven to 20 years post-operatively.[7,8] This is attributed to a reduction or elimination of daily drug therapy, restoration of normal sleep, reduction in anxiety, and lessened psychological distress and disorders.
5. What GERD treatment options are available?
The initial GERD treatment algorithm typically involves a combination of lifestyle changes, over the counter medications (OTC), and prescription drug regimens. Beginning with the initial visit, qualitative and quantitative benchmarks are established with the aim of exposing the patient to the lowest dose of medication as well as to identify extraesophageal GERD manifestations and other complications. For patients who are dissatisfied with their GERD medications, continue to have manifestations and/or complications, or are dissatisfied with the impact traditional treatment regimens have on their lifestyle, an anatomical solution is available.
5.1 Lifestyle:
Lifestyle modifications can significantly decrease the occurrence and severity of GERD in many patients and are usually the appropriate first step in the treatment process. Many of the known causes of GERD are directly related to diet, lifestyle, and everyday activities. By working with a physician, many patients are able to reduce the occurrence and severity of GERD symptoms by modifying their daily activities and behaviors.
5.2 Drugs:
Drug therapies such as proton pump inhibitors (PPI) or H2 (H2RA) blockers reduce ‘typical' GERD symptoms which are caused by acid exposure, but are not effective in treating non-acidic or alkaline reflux, and ‘atypical symptoms' like asthma, cough, or chronic obstructive pulmonary disease (COPD), since these symptoms result from the presence of reflux contents, regardless of the acidity. For some patients with motility disorders, prokinetic drugs, which help strengthen the esophageal motility and to some degree the lower esophageal sphincter and accelerate gastric emptying can also be helpful. Even if drug therapy is effective, patients will likely need drug therapy for the rest of their life, since symptoms and disease return as soon as medication is stopped.
5.2.1 OTC:
Some patients with mild, uncomplicated GERD can be appropriately treated with over -the-counter medications such as a combination of antacids, H2 receptor antagonists (H2RA) and, lately, OTC proton pump inhibitors (PPIs). Although H2RA's and PPI's were originally only available in prescription strength, in recent years lower doses have been approved for OTC sales. OTC medications are an easily accessible, palliative (pain reducing) option for people who suffer from occasional, mild to moderate GERD. Many OTC treatments work to neutralize the acid, reduce gas, and coat the lining of the esophagus and stomach thereby reducing the symptoms. These medications can be effective for reducing symptoms short-term. If GERD symptoms persist or worsen, it is important to see your doctor who will determine if a more aggressive approach is necessary.
5.2.2 PPI & H2RA:
Prescription medications offer many patients relief from the symptoms of GERD, but do not prevent alkaline and other stomach contents from entering the esophagus. Prescription doses of Proton Pump Inhibitors (PPI's) and/or H2RA's are effective palliative treatment options for moderate and recurrent heartburn because they reduce the amount of acid produced in the stomach.
Both PPI's and H2RA's work to inhibit secretion of acid by the parietal cells in the stomach mucosa. These medications, however, do not prevent neutralized acid from refluxing up into the esophagus, lungs, mouth, and/or nasal cavities. They also do not prevent reflux of other caustic agents, including bile, pepsin and digestive enzymes. While stomach tissue is designed to handle most of these caustic stomach acids, the tissue of the esophagus is. The continued reflux, although it doesn't ‘burn' because the acid is neutralized, may continue to damage esophageal tissue. In other words, medication treats the symptoms of GERD without addressing the root cause of GERD, reflux and regurgitation.
In addition, 10-20% of patients do not respond to these prescription medications and symptoms remain. Even on prescription medication, some patients are not able to eat large meals, eat late at night, drink alcohol, coffee, carbonized drinks etc., or eat fatty foods, chocolate, strawberries, or spicy foods without having symptoms return. Some patients may also have break-through symptoms at night, and regurgitate while sleeping. Some even find a pool of yellow fluid (bile) on the pillow when experiencing reflux at night. So called "silent aspiration" is often cited as the reason for GERD-related asthma. Raising the head of the bed is one option to help in reducing this nighttime reflux.
Some patients who respond well to prescription medication may find the efficacy of the drugs waning over time. The doctor may increase the dose of the drugs in efforts to obtain symptom control. Sometimes after increasing the dose a few times, it may be necessary to switch to a different medication to get control of symptoms again. The body has feedback loops designed to maintain balance, which sense the reduced acidity of the stomach contents and try to put out more acid. This feedback loop may be partially responsible for the loss of effectiveness of PPI's and H2RA's over time. Even in those patients where medication is highly effective, these medications must be taken every day if symptoms are frequent. When the medication is stopped, the effects of the drug also stop. Missing even a single dose can cause symptoms to reoccur. There can also be a delay between when medication is started and when the symptoms stop. In patients with severe GERD this can be quite problematic, since symptoms can remain for a few days after the start of medication.
6. What surgical solutions are available:
Open and laparoscopic surgical procedures are highly effective but are rather invasive, expensive, and adverse events like gas bloat syndrome and dysphagia are common. For this reason, less than 1% of the relevant GERD patients currently choose surgical therapy to treat GERD. Typically, open and laparoscopic surgeries have been performed on patients who suffer from severe GERD, whose symptoms occur almost every day, and who have tried lifestyle changes, OTC, and prescription medicines. Open and laparoscopic surgery carries surgical risk to patients and can result in side effects including pain, difficulty swallowing, the inability to belch or vomit. Despite these risks, surgical treatment of GERD has been utilized for more than 50 years and can be effective in up to 90% of patients.
Nissen fundoplication, introduced in 1951 as an open procedure, demonstrated that reconstructing the natural anatomy of the gastro-esophageal junction not only reduces the occurrence of symptoms but also improves the physiological conditions necessary to prevent reflux. In the early 1990's, the Laparoscopic Nissen Fundoplication (LNF) was introduced and became the most widely used surgical procedure for the treatment of GERD.[9, 10] LNF attempts to recreate the natural anatomy of the gastroesophageal junction as well as reduce hiatal hernia. In studies, LNF has been show to be effective in 75 to 90 percent of patients in alleviating heartburn and 50 to 75 percent in alleviating cough, asthma, and laryngitis.[11]
In addition, anti-reflux surgery has been shown to be superior to drug therapy in preventing Barrett's metaplasia.[12] The etiology of Barrett's metaplasia, a precancerous condition, presents strong evidence linking alkaline duodenogastric reflux to the development of esophageal mucosal damage which can best be prevented by restoring the ARB.[13]
Nissen, both LNF and open, requires significant changes to the natural anatomy in order to recreate the gastroesophageal valve. During the procedure, the fundus of the stomach, the short gastric vessels, and the phrenoesophageal membrane are typically dissected. The fundus is then wrapped around the esophagus and stitched to the anterior aspect of the stomach creating a loose wrap around the distal esophagus and the GEJ. Complications may include a long-lasting dysphagia, gas bloat syndrome, scarring, and, rarely, achalasia. The fundus is lost and belching may be impossible. In addition, LNF results in permanent anatomical modifications that are difficult to undo.
A 5-year longitudinal study of LNF determined the five-year cost-benefit of LNF to be higher in comparison with PPIs (omeprazol), largely due to the costs associated directly with the procedure itself as well as indirect costs, such as time away from work.[14] A recent UK study did conclude that by year eight the cost of LNF was break even with a PPI regimen and included as determining factors both the cost of the surgery (which may vary greatly) and the increase/decrease in cost and/or patient use of PPI into the future.[15]
The effectiveness and long-term cost-savings of LNF compared to a lifelong regimen of drugs demonstrate the need for an endoluminal solution to GERD that emulates LNF, but without incisions. Solutions are needed that provide substantive anatomical changes to restore the ARB and which address the underlying cause of GERD.
7. What about endoluminal approaches?
Until recently, endoluminal technologies for the treatment of GERD primarily focused on tightening the Lower Esophageal Sphincter (LES) with the aim of improving this component of the compromised antireflux barrier (ARB) through one of three methods:
- Thermal tissue remodeling by delivering radiofrequency
- Injection/implantation of resorbable material
- Plication of esophageal folds at the LES level by endoscopic suturing
- Many of these products were voluntarily removed from the marketplace due to unfavorable results and/or safety concerns.[16]
These previously mentioned technologies do not emulate surgery. EsophyXTM however is the first endoluminal therapy to provide:
- Reduction of hiatal hernia
- Creation of a robust antireflux barrier and valve resulting in serosa-to-serosa fusion
- Capability of creating numerous suture lines with multiple tissue fasteners
- Procedures that can be customized to the anatomy of the individual
8. What is TIF? (Transoral Incisionless Fundoplication)
EsophyXTM Transoral Incisionless Fundoplication (TIF) is the third wave in the evolution of surgical procedures for the treatment of GERD and builds upon the principles of open and laparoscopic surgical procedures. EsophyXTM TIF delivers similar benefits as the time-proven laparoscopic antireflux procedures, by reducing hiatal hernia, recreating the Angle of His, and creating a Gastroesophageal Valve (GEV). The key differences are that EsophyXTM TIF is a transorally performed non-invasive procedure (through the mouth), does not require incisions, and does not dissect any part of the natural internal anatomy.
EsophyXTM TIF is a surgical procedure for the treatment of GERD that aims to restore the antireflux (ARB) by creating a GEV. In addition to restoring the GEV, the EsophyXTM TIF procedure:
- establishes the Angle of His
- achieves serosa-to-serosa fusion
- lengthens the intraabdominal esophagus
- reduces hiatal hernia
While emulating principles of the Antireflux Surgery (ARS), the EsophyXTM TIF procedure is intended to reduce invasiveness, allow for faster recovery, and be more versatile than open or laparoscopic surgery.
The device has been designed to deploy multiple tissue fasteners to create a robust and durable ARB valve and the TIF procedures can be tailored for the specific patient and anatomy. Histological samples of preclinical studies confirmed that EsophyXTM TIF procedure creates a valve that incorporates serosa-to-serosa fusion.
In addition it could be demonstrated that the phrenoesophageal ligament is incorporated into the valves, stabilizing and strengthening the valve, firmly anchoring it to the diaphragm. Based on EU phase II Multi-Center data, EsophyXTM TIF procedures reduce adverse effects known from ARS like dysphasia and gas bloat syndrome, reduce pain, and reduce hospital stays as compared to ARS. EsophyXTM TIF is a very physiological approach to restoring the natural anatomical configuration of the ARB of the Gastroesophageal Junction (GEJ).
EsophyXTM TIF is an alternative to surgical, or pharmaceutical approaches to treating GERD. Because it is less invasive compared to surgery, EsophyXTM significantly expands the group of GERD patients that can benefit from an anatomical repair. Transoral Incisionless Fundoplication employs mechanical techniques to reinstate the anatomy observed in healthy individuals by restoring the mechanical gastroesophageal barrier, a GEV.
EsophyXTM is FDA cleared and CE marked, and available in the USA and the European Union. For more information please contact EndoGastric SolutionsTM by clicking the link below.
Citations:
[1] Reappraisal of the Flap Valve Mechanism in the Gastroesophageal Junction: A Study of a New Valvuloplasty Procedure in Cadavers, Thor, B.A., Hill Lucius D, Mercer, Dale D., and Kozarek, Richard D.; Acta Chir Scand 153: 25-28, ©1987
[2] Practice guidelines on the diagnosis, surveillance, and therapy of Barrett's esophagus. Sampliner R., Am J Gastroenterol 1998; 93: 1028-1032
[3] Efficacy of Medical Therapy and Antireflux Surgery to Prevent Barrett's Metaplasia in Patients With Gastroesophageal Reflux Disease, Gerold J. Wetscher, MD, Michael Gadenstaetter, MD, Paul J. Klingler, MD, Helmut Weiss, MD, Peter Obrist, MD, Heinz Wykypiel, MD, Alexander Klaus, MD, and Christoph Profanter, MD, Annals of Surgery Vol. 234, No. 5, 627-632 ©2001 Lippincott Williams & Wilkins, Inc.
[4] The Burden of Gastrointestinal Diseases, The American Gastroenterological Association, ©2001
[5] Cost-of-disease analysis in patients with gastro-oesophageal reflux disease and Barrett's mucosa. S. N. WILLICH, M. NOCON, M. KULIG*, D. JASPERSEN_, J. LABENZ, W. MEYER-SABELLEK, M. STOLTE-, T. LIND & P. MALFERTHEINER, Aliment Pharmacol Ther 23, 371-376. ©2006 The Authors 371Journal compilation 2006 Blackwell Publishing Ltd doi:10.1111/j.1365-2036.2006.02763.x
[6] The economic impact of GERD and PUD: examination of direct and indirect costs using a large integrated employer claims database. Vijay N Joish, Gary Donaldson, William Stockdale, Gary M Oderda, Joseph Crawley, Rahul Sasane, Sandra Joshua-Gotlib, Diana I Brixner. Curr Med Res Opin. 2005 Apr; 21:535-44.
[7] Quality of life for patients with gastroesophageal reflux disease 2 years after laparoscopuc fundoplication. S. Contini, A. Bertele, G. Nervi, R. Zinicola, C.Scarpignato. Surg. Endosc (2002) 16: 1555-1560.
[8] Surgery of Gastroesophageal Reflux Disease: A Competative or Complementary Procedure?, Lundell, Lars, Division of Surgery, Karolinska University Hsopital, Dig Dis 2004; 22: 161-170
[9] Laparoscopic Nissen Fundoplication, Glyn G. Jamieson, M.S., F.A.C.S., F.R.A.C.S., David I. Watson, M.B., B.S., F.R.A.C.S., Robert Britten-Jones, M.B., B.S., F.R.C.S., F.R.A.C.S., Philip C. Mitchell, M.D., F.R.C.S.C., and Mehran Anvari, M.B., B.S., F.R.C.S.C. From the University Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia; ANNALS OF SURGERY Vol. 220, No. 2, 137-145 ©1994 J. B. Lippincott Company
[10] Clinical Results of Laparoscopic Fundoplication at Ten Year After Surgery, Dallemagne, Bernard; CHC-Les Cliniques Saint Joseph, Digestive Surgery, Surg End
[11] Management of Gastroesophageal Reflux Disease, Joel J. Heidelbaugh, M.D., Timothy T. Nostrant, M.D., Clara Kim, M.D., and R. Van Harrison, PH.D., University of Michigan Medical School, Ann Arbor,Michigan, Am Fam Physician 2003;68:1311-8,1321-2. ©2003 American Academy of Family Physicians
[12] Efficacy of Medical Therapy and Antireflux Surgery to Prevent Barrett's Metaplasia in Patients With Gastroesophageal Reflux Disease. Wetscher, Gerold J. MD *; Gadenstaetter, Michael MD *; Klingler, Paul J. MD *; Weiss, Helmut MD *; Obrist, Peter MD +; Wykypiel, Heinz MD *; Klaus, Alexander MD *; Profanter, Christoph MD *. Annals of Surgery. 234(5):627-632, November 2001.
[13] Mixed Reflux of Gastric and Duodenal Juices Is More Harmful to the Esophagus than Gastric Juice Alone: The Need for Surgical Therapy Re-Emphasized. Werner K. H. Kauer, M.D., Jeffrey H. Peters, M.D., Tom R. DeMeester, M.D., Adrian P. Ireland, M.D., Cedric G. Bremner, M.D., and Jeffrey A. Hagen, M.D. Annals of Surgery Vol. 222, No. 4, 525-5333 ©1995 Lippincott-Raven Publishers
[14] The Cost of Long Term Therapy for Gastro-Oesophageal Reflux Disease: A Randomized Trial Comparing Omeprazole and Open Antireflux Surgery, Julkunen, K Levander, M Lamm, C Mattson, J Carlsson, N O Ståhlhammar and H E Myrvold, L Lundell, P Miettinen, S A Pedersen, B Liedman, J Hatlebakk, R, doi:10.1136/gut.49.4.488 Gut 2001;49;488-494.
[15] Short-term cost effectiveness and long-term cost analysis comparing laparoscopic Nissen fundoplication with proton-pump inhibitor maintenance for gastro-oesophageal reflux disease, R. Cookson1, C. Flood1, B. Koo, D. Mahon, and M. Rhodes, British Journal of Surgery 2005; 92: 700-706 Published by JohnWiley & Sons Ltd, ©2005 British Journal of Surgery Society Ltd
[16] Endoscopic treatment modalities for gastroesophageal reflux disease (GERD), B. H. A. von Rahden and H. J. Stein Department of Surgery, University Hospital, Paracelsus Private Medical University (PMU), Salzburg, Austria Received April 21, 2006; accepted July 17, 2006 © Springer-Verlag 2006, European Surgery.
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