Reflux of gastric contents to the esophagus is an event than can be put on a spectrum ranging from physiological to severely pathological leading to life threatening consequences. When reflux is pathological, it is referred to as gastroesophageal reflux disease (GERD). Due to little agreement as to what this term exactly includes, the Montreal Working Group issued a consensus statement defining GERD as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications; “troublesome symptoms” are defined as mild symptoms occurring two or more days a week, or moderate to severe symptoms occurring one or more days a week.
According to a review that included 15 epidemiological studies of GERD with strict inclusion criteria, GERD prevalence is 10-20% in the Western world, with an incidence of 0.5% per year. Not surprisingly, a steep increase in the incidence of esophageal adenocarcinoma, the most dreaded complication of GERD, has been observed. According to data from the Surveillance, Epidemiology, and End Results (SEER) Program, there has been a 56-fold, not 56%, but a 56-fold increase in the incidence of adenocarcinoma of the esophagus between 1984 and 2010. This high prevalence has led to enormous research about GERD and its optimal management options. There are clear, and potentially dangerous, misconceptions regarding this disease, and the purpose of this report is to address some of them.
Overview of GERD Symptoms, Diagnosis, and Management
The most common symptoms of GERD are heartburn, regurgitation and dysphagia. Other, less common symptoms of GERD include chest pain, hypersalivation, odynophagia, bronchospasm, laryngitis and chronic cough. GERD can be asymptomatic until complications reflecting advanced disease occur. Untreated or undertreated, GERD can lead to esophageal complications including erosive esophagitis, esophageal strictures as a result of chronic inflammation and healing, and Barrett’s esophagus, in which metaplastic columnar epithelium replaces the stratified squamous epithelium that normally lines the distal esophagus, predisposing to the development of esophageal adenocarcinoma. In addition, extra-esophageal complications may develop, including asthma (GERD is present in 34-89% of asthmatics), chest pain (i.e., noncardiac angina), hoarseness, globus pharyngeus (sensation of a lump or foreign body in the throat), chronic cough, and nonproductive throat clearing. Longstanding reflux can also lead to recurring pneumonia, chronic sinusitis, and voice changes.
The diagnosis of GERD can often be made empirically, based on a convincing clinical presentation with a good response to anti-acid therapy, making extensive radiologic and endoscopic investigations seemingly superfluous. Additional testing is needed to objectively confirm the diagnosis and severity of GERD, to assess for complications of GERD, and / or to establish alternative diagnoses.
The American Gastroenterological Association (AGA) recommends that endoscopy should be done for patients with GERD that have “alarm features” (e.g. dysphagia, odynophagia, gastrointestinal bleeding, anemia, weight loss) and for patients who have not responded to an empirical trial of twice-daily PPI therapy. Ambulatory pH monitoring is a “first-line” test to confirm or rule-out GERD in patients with or without symptoms, including those with symptoms persisting after initiation of PPI therapy and those who do not have evidence for mucosal damage on endoscopy. Ambulatory pH monitoring should be undertaken if proton pump inhibitor (PPI) therapy is considered for beyond the short-term. We have developed techniques to undertake endoscopy and Bravo pH probe placement in the office without sedation. This means patients do not lose control and are able to drive home or return to work immediately following the procedure.
Once GERD is diagnosed, lifestyle and dietary modifications are recommended, including weight loss, elevation of the head of the bed, avoidance of meals 2-3 hours before bedtime, selective elimination of dietary triggers that cause a relaxation of the gastroesophageal sphincter (such as fatty foods, caffeine, chocolate, alcohol, and peppermint), as well as smoking cessation. In a systematic review of six randomized trials, notably only weight loss and elevation of the head of the bed improved esophageal pH-metry and/or GERD symptoms. The next step in treatment usually involves anti-acid medications; the most commonly used being:
- Antacids, which neutralize gastric acid on contact, thereby decreasing (for a short time) the exposure of the esophageal mucosa to gastric acid during episodes of reflux.
- Surface agents, such as sucralfate, which adhere to and protect the gastric mucosal surface and protect it from peptic injury.
- Histamine – 2 receptor antagonists (H2RAs, H-2 blockers) decrease the secretion of acid by inhibiting the histamine 2 receptor on the gastric parietal cell, thereby reducing acid secretion.
- Proton pump inhibitors (PPIs) work by short-term irreversible binding to and inhibition of the hydrogen-potassium (H-K) ATPase pump of the gastric acid producing cells. They are the most potent inhibitors of gastric acid secretion. PPIs at standard doses for eight weeks relieve symptoms of GERD and heal esophagitis in up to 86% of patients with erosive esophagitis.
Traditionally, definitive control of reflux through surgical and/or endoscopic interventions were reserved for patients with complications of reflux such as recurrent or refractory esophagitis, stricture, Barrett’s metaplasia, persistent symptoms despite acid suppression, patients with GERD-induced asthma, as well as for patients unable to tolerate medication, noncompliant with medication, or unwilling to take lifelong medications
The most commonly used endoscopic intervention are Transoral Incisionless Fundoplication (TIF) and Stretta. We use these techniques selectively in patients that are not good surgical candidates because of serious medical comorbidities, for patients with a notable history of abdominal / gastric surgery, and for patients meeting strict eligibility requirements (e.g., a hiatal hernia of ≤ 2cm.
Laparoscopic anti-reflux surgery (e.g., laparoscopic Nissen fundoplication) is associated with very encouraging results from multiple centers across the United States. We have undertaken more than 2,000 of these operations over 25 years and have been very pleased by their efficacy and durability, and low complication rate. In recent years, robotics has been applied to anti-reflux surgery allowing surgeons with limited laparoscopic skills to safely undertake anti-reflux surgery through 4 to 5 small incisions. This is not our preference.
Our preference is a “scarless” laparoscoic approach: Laparo-Endoscopic Single Site (LESS) surgery. This approach allows for conventional laparoscopic operations to be undertaken through only one 12mm incision at the umbilicus, itself a scar. This approach has been very well received and results in less pain and a quicker recovery with a truly superior cosmetic outcome. Symptom control after LESS fundoplication is salutary, significant, and durable (note figure). “Scarless” anti-reflux surgery is possible only through this approach. We embraced this approach very early and have undertaken more anti-reflux operations using this approach than any other center in the United States, now more than 350 such operations. As experts in this surgical approach, we remain excited about the salutary benefits with outstanding cosmetic outcomes.
Misconceptions about PPI’s as a treatment for GERD
Despite documented efficacious outcomes after anti-reflux surgery, skeptics remain and promote the open-ended use of PPIs. However, enthusiasm regarding PPIs has led to their downsides being overlooked, and many misconceptions about them have spread, notably:
- Misconception #1:
“PPIs stop reflux.” Fact: They don’t. When used properly, they effectively eliminate gastric acidity in most people, but the reflux of gastric contents, which contain bile salts, continues. PPIs do not affect structural, mechanical, and motility abnormalities at the gastroesophageal junction responsible for gastroesophageal reflux (i.e. hiatal hernias, decreased lower esophageal sphincter pressure, transient lower esophageal relaxation). Therefore, PPIs do not decrease reflux; they simply change the acidity of the refluxate.
With PPI therapy, patients do not reflux acid, but rather bile salts and conjugated acids. These can cause heartburn and esophageal injury. In addition, because they still reflux, patients treated with PPIs still experience and suffer from some of the aforementioned extra-esophageal complications of reflux, such as asthma, pneumonia, laryngitis, chronic cough, dysphonia/hoarseness, globus pharyngeus, and nonproductive throat clearing.
- Misconception #2: “PPIs are harmless.” Fact: They are not. Long-term PPI therapy is associated with several complications:
- Community acquired colonic Clostridium difficile infections
- Community acquired and hospitalization-associated pneumonia >
- Magnesium malabsorption leading to hypomagnesemia has been documented in patients on prolonged PPI treatment, and an FDA safety alert has been issued in this regard.
- Calcium malabsorption resulting from hypochlorhydria has been documented, with an associated increased risk of low bone density (osteoporosis) and hip fractures. This is particularly a problem in postmenopausal women and men over 50 years of age.
- Vitamin B12 malabsorption.
- Iron malabsorption and iron-deficiency anemia.
- Acute interstitial nephritis.
- Dementia: a number of studies have found a significant association between use of PPIs and dementia
- Drug interactions: PPIs are metabolized via hepatic cytochrome P450 enzymes, with CYP2C19 having the dominant role. The activity of CYP2C19 is determined by gene polymorphism, and two known inactivating mutations which occur most commonly in Asian populations have been described. Five percent of Caucasians are homozygous for this mutation; as a result, the metabolism of drugs by this route may be delayed in these individuals, leading to higher plasma levels of PPIs in these patients with extended acid-suppression. While the latter sounds great, deleterious consequences may ensue, such as altered metabolism or activation of many drugs that are metabolized by the same pathway, including warfarin, diazepam, clopidogrel and phenytoin. In addition, PPIs may decrease the absorption of certain HIV protease inhibitors. Furthermore, the decreased acid environment of the stomach may limit pill or capsule degradation of some medications limiting their absorption.
- The reflux of unopposed bile salts and acids, possible because of acid suppression, can cause injury to the esophageal lining and predispose to adenocarcinoma of the esophagus, in part explaining the tremendous increase in the incidence of esophageal adenocarcinoma over the past 35 years.
- Misconception #3: “PPI’s are cost effective.” Fact: They are a huge economic burden. It is estimated that 11 billion dollars are spent annually on both prescribed and over the counter PPIs, an average cost of 60-160 dollars/month per patient. Moreover, a large proportion of the patients taking these drugs lack objective documentation of excess gastroesophageal reflux, and it is estimated that 30% of PPI prescriptions are appropriately prescribed.
In summary, GERD imparts a tremendous morbidity on our health system and our citizens. The indiscriminate and extended consumption of PPI therapy is not a solution, just a way to ‘kick the can down the road’, often to the tremendous detriment of the patients. Objective testing for reflux should be undertaken early to appropriately apply therapy, which should be definitive therapy for patients in need of ‘open-ended’ therapy or those with complications of reflux. Antireflux surgery is underutilized: it is efficacious, durable, and salutary.
By Alexander S. Rosemurgy, MD, FACS, Forat Swaid, MD, and Sharona B. Ross, MD, FACS
Dr. Rosemurgy has been a surgeon in the Greater Tampa Bay for almost 30 years. He has operated on over 27,000 patients and provided care and treatment to countless more from across the country. He is a thought leader in American Surgery, and has been a pioneer in minimally invasive surgery and Surgery of the foregut including esophageal cancer, reflux, achalasia, portal hypertension, liver tumors and pancreatic cancer. For more information or to refer a patient, please contact us at 813-615-7030.
More than 70 million Americans suffer from digestive disorders such as reflux, esophageal cancer, pancreatic cancer and many more. The Southeastern Center for Digestive Disorders and Pancreatic Cancer, Advanced Minimally Invasive and Robotic Surgery at Florida Hospital Tampa treats a wide variety of digestive conditions that include:
- GERD (Acid Reflux)
- Paraesophageal Hernias
- Esophageal Cancer
- Stomach Cancers and Tumors
- Small Bowel Disorders
- Gallbladder Disorders
- Hernias (Incisional and Inguinal)
- Pancreatic Cancer
- Bile Duct Disorders
- Liver Tumors (Hepatocellular Carcinoma and Metastatic Tumors)
- Portal Hypertension
- Complex Abdominal Disorders
The practice offers the most extensive experience in treating digestive disorders and pancreatic cancer in the Southeastern United States. We provide comprehensive care through a broad range of surgical techniques, including endo-lumnial, minimally invasive, robotic and open procedures. Pioneers and experts in Laparo-Endoscopic Single Site (LESS) and robotic surgery, Dr. Ross and Dr. Rosemurgy can provide patients with the most minimally invasive surgical procedures available today, many of which are “scarless” operations. Through innovative applications of anesthesia, they are able to operate on patients without the use of general anesthesia.