Preface

Gastroesophageal reflux disease (GERD) is the most common digestive disorder worldwide. Despite efforts made over the years in GERD treatment and prevention, GERD incidence is still growing steadily. According to the latest report, GERD increased by 77.53% globally during 1990–2019, from 440 million to 780 million. Most of the cases came from India and China, the two most populated countries, accounting for 180 million and 80 million cases, respectively. Due to the lack of a unifying standard for diagnosis, the actual number of GERD sufferers is likely much higher. Based on a recent meta-analysis, GERD potentially affects 0.9–1.1 billion people worldwide, which is about 14% of the current global population. The impact of GERD on word health and economy is great. In Europe, for example, GERD caused a 26% reduction in productivity, costing employers approximately 4.4 billion dollars in 2018.

GERD mainly affects two organs: the esophagus and the stomach. Although these two organs are neighboring parts of the digestive tract and both are involved in transporting food from the mouth to the intestine for digestion and absorption, they constitute a one-way street. Food can only go from the esophagus to the stomach, otherwise, it will cause damage to the epithelial lining of the esophagus because the ingested food becomes highly acidic once reaching the stomach. The squamous epithelium in the esophagus is not made to stand such a highly acidic condition and, as a result, esophagitis develops. When these reflux episodes take place again and again, the esophageal lining gradually changes from squamous to columnar, becoming the intestinal-like phenotype, which is called Barrett's Esophagus. When this happens, the patient is 400 times more likely to develop esophageal cancer.

The lower esophageal sphincter (LES) is a muscular structure sitting between the esophagus and the stomach that prevents the stomach content from going into the esophagus. Therefore, anything that interrupts LES function is a potential cause of GERD. Obesity or overweight is the number one factor. The excessive weight in the abdominal region puts constant pressure on the stomach, forcing the stomach content to break the LES barrier and erupt into the esophagus, causing esophagitis. Other factors include eating habits, lifestyle, taking certain drugs, esophageal or gastric motility weakness, and so on. Some common food and drinks (e.g., coffee, tea, soda, juices, alcoholic beverages, chocolates, tomatoes, high-fat or high-calorie food, or spicy food) can create occasional GERD episodes in healthy individuals or worsen the condition of GERD patients. Many medications can also interfere with the LES function and result in GERD symptoms, such as nitrates, calcium channel blockers, anticholinergic drugs, benzodiazepines, nitroglycerin, albuterol, antidepressants, glucagon, and non-steroidal anti-inflammatory drugs (NSAIDs).

For these reasons, the current strategies for GERD management and prevention mainly rely on changing eating habits, modifying lifestyle, suppressing gastric acid secretion, and surgically restoring LES function. However, none of these have achieved satisfaction so far. GERD incidence is still growing day by day, year after year. Why? Let's look at these strategies one by one.

**Chapter 1**

**1. Introduction**

Introductory Chapter: Do We

Gastroesophageal reflux disease (GERD), commonly known as heartburn, has been one of the most prevalent digestive disorders for the past few decades. Despite various definitions in different parts of the world, GERD generally refers to the effortless movement of stomach contents into the esophagus causing troublesome symptoms, typically a burning sensation in the chest, which may radiate toward the neck, throat, and the back, inducing pain. Chronic GERD can lead to several complications, including erosive esophagitis, esophageal strictures, and esophageal epithelial transformation into Barrett's Esophagus (squamous epithelium turning into columnar epithelium), a precancerous condition to adenocarcinoma. Therefore, early diagnosis and proper treatment are critical for the prevention of these potential complications and malignancy. Due to its popularity, GERD has not only deteriorated the quality of life for many people all over the world, but it has also brought up tremendous economic pressure on many countries and regions. European Digestive Health Summit 2018 reported a 26% reduction in productivity across Europe because of GERD, costing employers ~\$4.4 billion [1]. In the United States, the expenses on

Really Know GERD?

GERD were estimated to be at least \$24 billion/year [2].

**2. How many people are affected by GERD? we do not know**

There has never been a unifying definition for GERD; consequently, GERD diagnosis has never had a gold standard. Mostly, it is made based on questionnaires in combination with a few additional examinations and tests, including responsiveness to acid-suppressive drugs, esophagogastroduodenoscopy (EGD), and ambulatory reflux monitoring. Weekly heartburn or acid regurgitation is the first indicator of GERD. Heartburn refers to a retrosternal burning sensation that typically occurs after a meal or when in a reclined position, and regurgitation is the backflow of stomach contents into the mouth or throat. However, some GERD patients are asymptomatic. As reported in Europe, 44–46% of the patients with Barrett's Esophagus never showed any sign of heartburn or acid regurgitation [3]. Among those presenting these symptoms, on the other hand, a significant proportion is caused by other pathological conditions rather than GERD. As evidenced in the United Kingdom, only 66% of the patients with heartburn or regurgitation were confirmed to be GERD by endoscopic examination and 24-hr pH monitoring [4]. Likewise, among the real GERD patients, only 49% ever experienced heartburn or

*Xianmei Meng and Jianyuan Chai*

First, let's ask ourselves a question: can we really quit eating and drinking coffee, tea, soda, juice, alcohol, chocolate, tomatoes, and high-fat, high-calorie, or spicy food? Will we still be able to enjoy our lives if we eliminate these foods and beverages from our daily diet? We have been eating and drinking this stuff for generation after generation, for as long as we can remember. Giving all these up is impossible for most of us and thus we must think of a new way to deal with the problem of GERD.

Now, let's look at acid-suppressive drugs. From antacids to H2 blockers (famotidine and cimetidine) to proton pump inhibitors (omeprazole, lansoprazole, esomeprazole, pantoprazole, dexlansoprazole, and rabeprazole), the basic idea is to lower or neutralize gastric acid secretion and thereby reduce the esophageal damage caused by refluxes. First, we must know that pathological GERD is not due to acid secretion. We need gastric acid to sterilize our ingested food and create a suitable environment for enzymatic digestion. Acid suppression will definitely interfere with these purposes. Growing evidence has shown multiple side effects in association with taking acidsuppressing drugs, including decreased absorption of vitamins/minerals, susceptibility to infections, bone fracture, and even greater risk of developing cancer. Once they stop taking these drugs, 70%–100% of patients will experience GERD episodes again. We must think of a new way to deal with the GERD problem.

Laparoscopic Nissen Fundoplication is now considered to be the gold standard for the surgical treatment of GERD. This is a great idea because this procedure intends to solve the problem by restoring LES function so that gastric contents will be unable to get into the esophagus. However, this technique has not gained success as expected. After surgery, many patients have developed postoperative adverse symptoms such as bloating, dysphagia, and belching. As a result, 62% of patients had to go back to taking acid-suppressive drugs. We must think of a new way to deal with the GERD problem.

Compared to all these therapeutic ideas, modifying lifestyle seems the most achievable. We can do more exercises to control our weight, we can avoid lying down right after meals, we can raise our pillows before sleep, and so on. These actions are typically easy to implement; however, will they eliminate GERD? Unfortunately, the answer is no. We must think of a new way to deal with the GERD problem.

This book provides a comprehensive overview of GERD and discusses the various techniques employed to relieve associated symptoms.

> **Jianyuan Chai** Professor, Inner Mongolia Institute of Digestive Diseases, Baotou Medical College, Baotou, China
