Heartburn, GERD, Barrett’s Causes, Diagnosis and Treatment Jacque F Noel, MD Gastroenterologist

Heartburn Diagnosis Heartburn is an occasional condition with mild to moderate symptoms, usually of a burning sensation in the chest. Heartburn is often confused with indigestion. Although the two are related, indigestion is caused by general stomach upset, while heartburn is the burning sensation caused by gastric acid backing up into the esophagus. Diagnosis is made by frequency and intensity of discomfort, and a history of lifestyle and dietary habits assists in identifying heartburn triggers.

Common Heartburn Triggers Coffee Carbonated drinks Acidic foods Citrus foods Tomato products Chocolate, mints Fried or fatty foods Onion, garlic and spicy foods Certain medications, including aspirin or ibuprofen Alcohol Smoking Eating too much or too quickly Lying down soon after eating a large meal Pregnancy Excess weight-especially in abdominal area

Heartburn Treatment Most importantly, heartburn is an OCCASIONAL condition with mild to moderate symptoms. Occasional heartburn should be easily relieved by OTC antacids and moderate lifestyle and dietary changes. Additional tips for minimizing heartburn symptoms include: Wear loose-fitting clothing around waist Eat smaller, more frequent meals Raise the head of bed by putting blocks under headboard legs Limit the food and beverages that worsen symptoms Stop smoking and/or drinking alcohol Strive to lose excess weight

Heartburn Progression Heartburn symptoms are similar to those of GERD, a more serious condition. Some cardiac problems may also present with similar symptoms. The patient being treated for heartburn should be advised that persistent problems despite treatment signals a more serious condition, and should contact their physician if they experience: Heartburn that: Occurs twice a week or more Increases in intensity/discomfort Persists after taking antacids Returns as soon as the antacid wears off Wakes individual up at night Difficulty swallowing

Gastroesophageal Reflux Disease GERD Diagnosis GERD occurs when contents in the stomach flow back in the esophagus. This happens when the valve between the stomach and the esophagus-the lower esophageal sphincter (LES)-does not function properly The GERD diagnosis is distinguished from Heartburn by frequency and intensity-GERD is suspected when symptoms are occurring frequently versus occasionally and with more intense symptoms; symptoms are not being relieved by OTC antacids and modified lifestyle changes

Gastroesophageal Reflux Disease GERD Diagnosis (continued) Less common symptoms that may also be associated with GERD include unexplained chest pain, wheezing, sore throat, hoarseness and cough. There is also a proven correlation between sleep apnea and increase in GERD. Untreated GERD can allow development of the following: Ulcerative esophagitis Esophageal Strictures Barrett’s Esophagus Esophageal Cancer

What causes GERD? Gastroesophageal Reflux Disease occurs when there is an imbalance between the normal defense mechanism of the esophagus and the offensive factors of acid and other digestive juices and enzymes in the stomach. Situations that can contribute to the development of GERD include: LES (lower esophageal sphincter) malfunction Hiatal Hernia Excess abdominal fat increasing pressure on stomach Lifestyle and dietary habits Sleep apnea

Complications of GERD The goal of getting proper treatment for the patient with chronic reflux – GERD – is to promptly diagnosis the condition and attempt to eliminate the condition before inflammatory changes begin to occur in the esophagus from the invasion of acid in the stomach. Early signs of these changes would be seen during upper endoscopy as redness and irritation of the tissue (esophagitis) which can be mild or severe and be manifested by the presence of ulcers (ulcerative esophagitis). Strictures commonly form in the esophagus due to the inflammatory process and the patient may have difficulty swallowing or a sensation of food or medicine sticking or “hanging up” in the esophagus. Treatment with prescription medications and needed esophageal dilatation may be needed in these cases. Untreated GERD over time, allows development of Barrett’s Esophagus

Treatment of GERD Once patient presents with symptoms of GERD, not responding to conservative treatment of OTC medications with lifestyle and dietary changes, additional tests prior to initiating a treatment plan are recommended Diagnostic treatments prior to treatment could include: Upper endoscopy: Allows physician to visualize esophagus and stomach for structural abnormalities such as a hiatal hernia or open LES and detect an evidence of esophageal damage due to reflux, biopsies and/or brushings can be taken to check for microscopic signs of tissue damage pH Testing A small sensor attached to the esophagus during upper endoscopy or a pH probe placed into the esophagus at another time measures acid content in the esophagus for a 24 he period, sowing frequency, time and extent of reflux

Treatment of GERD After definitive diagnosis of GERD has been made, a treatment plan can be determined. Incorporating the dietary and lifestyle changes previously discussed and elevating the head of the bed for sleep are recommended in addition to three central areas of treatment Medication-commonly proton pump inhibitors (PPIs) alone or in combination Endoscopic anti-reflux therapy (endoluminal therapy or transoral incisionless fundoplication) Anti-reflux surgery (laparoscopic or open fundoplication)

Barrett’s Esophagus Biopsies may be taken to look for migration of gastric cells into the esophagus. This migration is a protective mechanism that develops due to chronic inflammation resulting from GERD, and the development of this change indicates a condition called Barrett’s esophagus. It becomes visible at he EG junction and then migrates upward in “tongue-like” protrusions resembling the tongues of a flame Barrett’s is more common in patients who have long-standing GERD. It is interesting to note that the frequency and intensity of GERD symptoms, such as heartburn, does not affect the likelihood of someone developing Barrett’s. As the gastric cells may replace esophageal cells, the symptoms of reflux actually decrease, although inflammation and damage is still progressing. In some patients with Barrett’s esophagus, a precancerous change in the tissue, dysplasia, will develop. Patients with dysplasia are more at risk for developing esophageal cancer.

Diagnosing Barrett’s At the current time, a diagnosis of Barrett’s can only be made using endoscopy to detect a change in the lining of the esophagus (Barrett’s tissue has a different appearance than normal esophageal tissue and is visible during endoscopy) and taking a tissue sample of the abnormal appearing areas by biopsy or brushings. The pathology interpretation is required to confirm the Barrett’s diagnosis.

Who should be screened for Barrett’s? Barrett’s is twice as common in men as women. It most commonly occurs in middle-aged Caucasian men with a history of heartburn for many years. Current recommendations suggest screening endoscopy for patients older than 50 with a history of significant heartburn or those who have required regular use of medications to control heartburn for several years. If that first screening is negative, another is not recommended for several years, but aggressive steps should be taken to eliminate GERD in the patient.

Following diagnosis of Barrett’s Once a patient has had a confirmed Barrett’s diagnosis, they are put on a repeat endoscopy schedule at set intervals determined by the physician based on the extent of Barrett’s present Multiple tissue samples are taken at levels of Barrett’s tissue to search for abnormal cells of dysplasia, a precancerous condition that can only be diagnosed by pathology interpretation. The interpretation will describe any dysplasia seen in the samples as being “high-grade,” low-grade” or “indefinite (or indeterminate) for dysplasia. High-grade dysplasia – indicates that abnormal changes are seen in many of the submitted cells and there is an abnormal growth pattern of the cells Low-grade dysplasia – means that there are some abnormal changes seen in the submitted tissue sample, but the changes do not involve most of the cells and the growth pattern of the cells is normal Indefinite (or indeterminate) for dysplasia – means that the pathologist cannot determine whether changes seen in the tissue are caused by dysplasia. Other conditions, such as inflammation, can make cells appear dysplastic when they may not be.

What is the risk for Esophageal Cancer? There are two types of esophageal cancer: squamous cell cancer and adenocarcinoma Squamous cell esophageal cancers occur most commonly in individuals who smoke cigarettes, use other tobaccos products or drink alcohol. In addition, African Americans are more at risk for development of this type of esophageal cancer; it is additionally very common in Asia. The frequency of squamous cell cancer of the esophagus in the United States has remained the same for many years; the decline of smoking in the population should show a decrease in the diagnosis Adenocarcinoma of the esophagus occurs most commonly in patients with long-lasting GERD-again most common in middle aged Caucasian males with excess abdominal girth. Adenocarcinoma of the esophagus is increasing in frequency in the United States in the last 10 years. It is estimated that 20% of American adults experience reflux symptoms at least twice a week. The majority of these people treat themselves for years with antacids, avoiding certain foods and sleeping in a recliner after a large meal, etc. Most only seek medical attention after no longer being able to tolerate the discomfort or developing a symptom such as difficulty swallowing. Although these individuals are at increased risk for developing esophageal cancer, the vast majority will not. In about 10-15% of patients with GERD, esophageal cells will change in response to repeated acid reflux and the Barrett’s condition will develop. Physicians now know that most cases of adenocarcinoma of the esophagus develop from Barrett’s esophagus The risk of esophageal cancer developing in Barrett’s patients is about 1 out of 200 per year, with the risk increasing 0.5% per year thereafter without intervention The risk is high enough that Barrett’s patients are advised to undergo periodic upper endoscopy with random biopsies of Barrett’s tissue to identify any dysplasia at the earliest possible stage

Barrett’s Surveillance for Dysplasia Looking for a needle in the haystack Interval surveillance with random forceps biopsies for dysplasia is the clinical standard for the management of patients with Barrett’s esophagus. Since dysplasia as no gross distinctive features, even strict adherence to “Seattle Protocol” for sample collection tests only 2-3% of the epithelium in targeted areas of the esophagus. Obviously, this leaves the majority of Barrett’s tissue untested, and a source of concern for the physician and patient. In an effort to overcome the problem of sampling error, specialty labs have developed in the last few years to specifically address this issue of concern. Last year at our facility, we chose to participate in a study wit EndoCDx® where a “WATS brush biopsy”, which obtains a “wide-area” tissue sample was taken in addition tot eh random forceps biopsy surveillance protocol on patients with Barrett’s This type of brush tissue collection was also used to obtain samples from GERD patients to test for the presence of Barrett’s, which can be difficult to diagnose from biopsy of small segments of Z-line irregularity Two things to note as an observation from the collection process—the techs that assist in obtaining the samples were trained in the technique—the brushings are collected in an aggressive “sawing-like” motion covering the entire area in question Additionally, the brush used has bristles that are much longer and stiffer than a standard cytology brush

ENDO CDx Sample Analysis The collection of the “wide-area” tissue sample increases the yield of abnormal findings in the esophagus and significantly reduces the “random” part of the interval surveillance of existing Barrett’s patients. Additionally, the analysis of the WATS tissue samples is aided by a proprietary high speed computer scan, originally developed for the missile defense industry The computer is able to identify abnormal cells when they pass through the high speed 3-D scan and isolate them – even when the cells are over-lapping. These specialized computers have routinely shown the ability to identify as few as 2 dysplastic cells in 100,000. Independent published clinical data has shown that, when used in conjunction with and compared to traditional forceps biopsy, the WATS biopsy detects an additional 39% of Barrett’s cases and 42% more diagnosis of dysplasia. Although our facility is still in the process of collecting enough data for a valid study comparison, it has been noted that we have seen more confirmed new cases of Barrett’s tissue in GERD patients as well as confirmed dysplasia in surveillance patients with existing Barrett’s.

ENDO CDx Sample Analysis

ENDO CDx Sample Analysis Unlike Cytology, WATS3D Obtains Complete Transepithelial Biopsy of the Entire Thickness of the Esophageal Mucosa Limitations of Standard Esophageal Cytology

Treatment For Barrett’s Esophagus Obviously the goal is to have physician intervention early in patients experiencing chronic reflux to prevent progression of Barrett’s disease, dysplasia or esophageal cancer. Medications and anti-reflux procedures/surgery can effectively control the symptoms of GERD, but neither can reverse the presence of Barrett’s esophagus or eliminate the risk of cancer associated with the diagnosis. Much research is presently being conducted in the area of treatment modalities to destroy Barrett’s tissue and eliminate this risk. Some methods are currently available, producing good outcomes and gaining favor with physicians and patients, but as of now there is no “Gold Standard” treatment accepted by a vast majority of physicians in the field. Current modalities include heat (radiofrequency ablation, thermal ablation with argon plasma coagulation and multipolar agulation), cold energy (cryotherapy) or the use of light and special chemicals (photodynamic therapy).

Treatment For Barrett’s Esophagus There has been an increase in the use of endoscopic techniques to locally remove Barrett’s tissue – endoscopic mucosal resection (EMR). The physician’s choice of treatment is based on extent of Barrett’s, pathology reports, availability and effectiveness of treatment and willingness and cooperation of patient in undergoing treatment. The partners at our facility were very interested in offering a treatment option to our Barrett’s patients. After evaluating research, published data, outcome statistics and speaking with GI colleagues, the Halo®Radiofrequency Ablation System seemed the best fit for our facility. The physicians did on-site visits to facilities using the system and then attended training to be certified in the technique. It is now being used in our endoscopy center and partner hospital.

HALO® Radiofrequency Ablation Halo ablation technology uses heat to eliminate diseased Barrett’s tissue. By targeting only Barrett’s tissue, the minimally invasive procedure leaves healthy tissue intact. Halo uses radiofrequency energy to deliver heat through a catheter to eliminate diseased tissue without harming healthy structures underneath it. While the patient is under conscious sedation, the gastroenterologist will insert an endoscope into the patient’s mouth. Depending on the extent of the Barrett’s the physician will choose either a balloon mounted Halo -360 catheter or an endoscope –mounted Halo-90 catheter which is plugged into a generator that delivers the radiofrequency energy. The Halo-360 has a balloon that is covered by a band of radiofrequency electrodes and is used to treat larger areas of Barrett’s. The Halo-90 the electrode is positioned on the smaller area of diseased tissue to deliver the energy.

HALO® Risks and Benefits The Halo radiofrequency ablation procedure is considered very safe. Patients may experience minor side effects, such as chest discomfort and swallowing difficulty for several days following the procedure. The physician provides the patient with diet instructions and medications to manage these symptoms, which usually go away in 3-4 days post treatment. Benefits: Data suggests elimination of Barrett’s tissue in 98.4% of patients (some require follow-up applications to smaller residual areas New, healthy tissue growth occurs 3-4 weeks post-procedure Quick recovery period with minimal side effects Minimally invasive, outpatient procedure No general anesthesia required Low rate of post-procedure complications Risks: Mucosal laceration Infection Narrowing of the esophagus Minor acute bleeding

HALO® Risks and Benefits Data has suggested HALO as a treatment option for Barrett’s disease with pathology detecting no dysplasia and few low dysplasia cells. A pathology finding of high grade dysplasia requires a higher level of aggressive treatment and patients in our practice would be referred for evaluation with EUS and either EMR or surgical intervention, dependent of findings from EUS.

Proton-Pump Inhibitors PPIs are the mainstay of anti-reflux treatment. PPIs are prescribed for once or twice daily use for significant reflux and may be reduced to “PRN” use when symptoms are under control. A large number of PPIs are available and frequently individuals respond and/or tolerate one brand over another When reflux is particularly difficult to control, other types of medications (prokinetics of H2-blockers) may be added to the medication regime to achieve better symptom reduction For those patients with severe GERD symptoms that can’t be controlled with medication, some type of procedural intervention or surgery may be indicated. Lifestyle Changes Pharmaceuticals Procedure Intervention Surgery Severe GERD MILD Early disease, no correction required Anatomic correction warranted

Endoscopic Anti-Reflux Therapy Stretta Procedure The Stretta procedure is a minimally invasive, endoscopic procedure that takes about 60 minutes to perform It is done on an outpatient basis, and patients typically for home 1-2 hours following procedure Under sedation, a flexible catheter is inserted through the mouth into the esophagus and is positioned at the lower esophageal sphincter valve at the junction to the stomach. The catheter has 4 small needles which deploy into the muscle of the LES and deliver radiofrequency energy into the muscle. Several areas in the region of the LES and cardia of the stomach are treated to create small thermal lesions Over time the lesions heal, causing collagen deposition in the area resulting in thickening of the LES area and surrounding muscle tissue Clinical studies show improvement in GERD symptoms at the 3 to 4 month post-procedure point, with acid exposure and elimination or reduction in the use of reflux medications continuing to improve until the 6 month period before stabilizing

Endoluminal Therapy: Stretta Pros: Minimally invasive-no incisions Does not require general anesthesia Outpatient procedure with minimal recovery Low risk of complications May be beneficial for gastroparesis May be repeated if required Does not limit future treatment options Cons: Contraindicated in patients with large hiatal hernias, erosive esophagus and severe dysphasia Small perforation risk May be minimally effective Results take time to evaluate

Endoluminal Gastroplication Surgery (ELGP), EndoCinch, (BARD); ESD, (Wilson-Cook) In the ELGP procedure, an experienced endoscopist or surgeon uses transoral endoscopic visualization and the suturing delivery system to place a series of adjacent mucosal sutures in opposition below the squamocolumnar junction. The adjacent sutures are then tied together, forming a plication (or “cinching”) which alters the tension on the valve, thus reducing the acid flow back from the stomach into the patient’s esophagus Upon first release after FDA approval, technical challenges in the knot tying of the sutures caused a large number of these plications to come undone. Additionally, the configuration of the plication’s directly affects outcome and results were widely varied based on the suture pattern and dexterity of the operator It appears, however, that the second-generation device has simplified the suture placement and knotting technique required—resulting in improved and more consistent outcomes

Endoluminal Gastroplication Surgery (ELGP), EndoCinch, (BARD); ESD, (Wilson-Cook) Pros: Minimally invasive-no incision Does not require general anesthesia Outpatient with minimal recovery Does not limit future treatment options Low risk of complications Cons: Operator-dependent results Sutures may come undone May be ineffective

Transoral Incisionless Fundoplication (TIF); Esophyx TIF is a surgical procedure performed through the mouth without incisions The procedure is typically performed in an outpatient setting under general anesthesia EsophyX is a form of Natural Orifice Surgery (NOS) and the device creates an esophagogastric fundoplication that is up to 270 degrees and 3 cm in length requiring no incisions In essence, the procedure reconstructs the antireflux valve at the EG junction, preventing reflux Unlike other endoluminal therapies that are solely focused on the LES, the TIF procedure reconstructs the dynamics of the body’s antireflux barrier similar to the Nissen procedure, with no internal dissection of natural anatomy

TIF Procedure http://www.youtube.com/v/vTUNwaZtILY

TIF;EsophyX Pros: Transoral, incisionless procedure Fast recovery Few complications Can be revised if required Does not limit future treatment options Cons: Small risk of perforation, sore throat, bleeding, N&V, swallowing difficulties Requires general anesthesia

Anti-reflux Surgery (Laparoscopic) LINX Procedure The LINX Reflux Management system is a medical device for use in patients 21 years and older who have been diagnosed with GERD and continue to have problematic symptoms of reflux despite treatment with medication or who have been on long-term medical therapy and are concerned about effects of long-term treatment The LINX device uses a small flexible band of magnetic beads that is implanted around the LES during a laparoscopic procedure When placed around the outside of the esophagus at the EG junction, the magnetic attraction between the beads keeps the sphincter stay close to prevent reflux The force of a swallow, belch or vomiting causes the beads to open, then close when pressure is relieved

LINX Procedure

LINX Pros: Minimally Invasive Well-tolerated Removable Patient able to eat a normal diet after surgery Few complications Does not limit future treatment options Cons: General anesthesia Band could migrate or erode into tissue

Laparoscopic Nissen Fundoplication When a surgical fundoplication is performed, the part of the stomach (the fundus) closest to the entry of the esophagus is gathered, and wrapped around the lower end of the esophagus and the LES, where it is sutured into place This technique strengthens the LES to prevent the malfunction that is causing GERD It is usually performed when medical therapy has failed, and is the first-line procedure when the patient also requires repair of a sizeable hiatal hernia The Nissen procedure is the most common fundoplication and involves a total 360 degree wrap used for GERD treatment A Dor or Toupet, in contrast, are partial fundoplication's used to correct achalasia If a patient has a hiatal hernia, it is repaired in conjunction with the fundoplication by pulling the herniated segment of the stomach from the chest and anchoring it with suture so that it is secured in the abdominal cavity

Laparoscopic Nissen Fundoplication The opening in the diaphragm through which the esophagus passes from the chest into the abdomen is also tightened The laparoscopic Nissen procedure is performed under general anesthesia and requires only 5 small holes in the abdomen where instruments and illumination enter into the operative site The advantage of the laparoscopic surgery is a speedier recovery and less post-operative pain The procedure usually takes somewhat longer that the open method and is harder for the surgeon to judge precisely how tight the wrap is around the esophagus Occasionally, a laparoscopic procedure will be switched to an open procedure by the surgeon if difficulty or complications are encountered

Open Nissen Fundoplication The open surgery Nissen Fundoplication requires a 4-8 inch upper abdominal incision The open method of Nissen has been greatly outnumbered by the laparoscopic version of the surgery due to the patient benefits Some surgeons prefer the open procedures, especially in obese patients and that that require hiatal hernia repair During open cases, surgeons may place a mesh to repair the enlarged diaphragm opening that allows the stomach access to the chest cavity Additionally, the surgeon can make a better determination of how tight or loose the wrap is around the LES

In Review Heartburn Occasional condition with mild to moderate symptoms of burning sensation in chest Successfully treated with OTC medications, dietary and lifestyle changes Does not increase in frequency or intensity of discomfort

In Review GERD Occurs frequently-twice a week or more Moderate to severe increase in intensity/discomfort Non-cardiac origin confirmed Persists after taking antacids or returns as soon as antacid wears off Wakes individual up at night Causes swallowing difficulty Common causes include: LES malfunction, Excess abdominal fat, Lifestyle and Dietary habits, sleep apnea Physician evaluation of cause and treatment to prevent GERD critical in preventing esophageal damage from reflux, such as esophagitis, ulcers, strictures, Barrett’s

In Review GERD Diagnostic testing may include: upper endoscopy, PH Testing Dietary and lifestyle modifications important in treatment plan Additional therapies include three central areas of treatment: Medication (PPIs or combinations) Endoscopic anti-reflux therapy (Stretta, Endoluminal Gastroplication-ELGP) Anti-reflux surgery (Transoral Incisionless Fundoplication –TIF, Linx Procedure, Laparoscopic and Open Nissen Fundoplication) Failure to control GERD increases risk of developing Barrett’s esophagus, and possible risk of esophageal cancer

In Review Barrett’s Esophagus Develops due to chronic inflammation from esophageal exposure to acid. Gastric cells migrate into esophagus causing cellular changes resulting in Barrett’s. Diagnosed by upper endoscopy with tissue samples for pathology evaluation More common in middle aged Caucasian men with abdominal fat and long-standing history of GERD symptoms Once diagnosis of Barrett’s is confirmed by pathology, patients are placed on a scheduled surveillance timeline for repeat endoscopy with random biopsies to screen for development of dysplasia, a precancerous condition Diagnosis of Barrett’s increases risk of esophageal cancer development Specialty pathology (ENDO CDx) collection and analysis techniques can be utilized to increase confirmation of first-time Barrett’s and presence of dysphasia in existing Barrett’s cases Current available treatment methods to destroy Barrett’s tissue: Heat (radiofrequency ablation, thermal ablation, argon plasma coagulation, multipolar agulation), Cold energy (cryotherapy), or the use of light and special chemicals (photodynamic therapy) Discussion of use of Halo therapy – a method of destroying Barrett’s tissue in use at presenter's facility

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