Preface

**Section 3 Other Disorders of the Esophagus 117**

Chapter 7 **Congenital Diseases of Esophagus 119**

Grati, Ali Amouri and Nabil Tahri

**Department 131**

**VI** Contents

Chapter 9 **Caustic Ingestion in Children 151**

**Section 4 Esophageal Tissue Engineering 171**

Chapter 11 **Tissue Engineering of Esophagus 173**

Yabin Zhu, Mi Zhou and Ruixia Hou

Chapter 10 **Lymphocytic Esophagitis 163**

Mehrdad Hosseinpour and Bahareh Ahmadi

Mesa-Magaña and Edgar M Vasquez-Garibay

Dane Christina Daoud and Mickael Bouin

Chapter 8 **Prescription of Proton Pump Inhibitors in Elderly Subjects in Real Life: A Retrospective Study in a Gastroenterology**

Mona Boudabous, Héla Gdoura, Leila Mnif, Lassad Chtourou, Amal

Alfredo Larrosa-Haro, Carmen A Sánchez-Ramírez, Johnatan M

The word *esophagus* (or oesophagus) derives from twoGreek words, *eosin* and *phagos,* mean‐ ing to carry and eat. Now itrefers to the tubular structure between thepharynxand thestom‐ ach. It begins at the back of the mouth, goes down behind the mediastinum, passes through the diaphragm, and ends into the stomach. There is a muscular ring at each end, known as the upper esophageal sphincter and the lower esophageal sphincter, respectively, which controls what gets in and what gets out. With the aid from peristaltic contractions, this pipe sendsfood to a long journey of digestion.

We open this book with the chapter "Anatomy of the Esophagus," written by Dr. Fehatoglu and Dr. Kivilcim (Okan University, Turkey), because we think it is absolutely essential to have such knowledge before getting into the rest of the book.

In human adults, the esophagus is about 25 cm in length, with a wall consisting of the muco‐ sa, the submucosa, the muscularis propria, and an outer layer of connective tissue called the adventitia. The mucosa is astratified squamous epithelium composed of three layers of squ‐ amous cells, which can be easily distinguished from thesingle layer of columnar cellsof the stomach at the gastroesophageal junction. Unlike in other animals, the human esophageal epithelium is not covered with keratin, because it needs to turn over rapidly to minimize the abrasive effects of food. Within the esophageal wall, there are glands producing mucus to facilitate food passing through.

When food is being swallowed, the upper sphincter relaxes, allowing food to enter the pipe. Peristaltic contractions of the esophageal muscle push the food down through the lower sphincter into the stomach. The lower esophageal sphincter is like a dam sitting in between the esophagus and the stomach to prevent the stomach contents to back up into the esopha‐ gus. When this muscular structure does not hold well, gastroesophageal reflux disease (GERD) takes place, in which case stomach acid mixed with duodenal content gets into the esophagus. If this happens frequently and substantially enough, it can lead to esophagitis and then to Barrett's esophagus, a premalignant metaplasia of the esophageal lining chang‐ ing from stratified squamous epithelium to simple columnar epithelium. Compared to nor‐ mal people, individuals with Barrett's esophagus can have as high as 400-fold increased risk to develop esophageal cancer.

Esophageal cancer is globally ranked as number nine by its prevalence and number six by its mortality. Therefore, we dedicate the next five chapters of the book to this deadliest dis‐ ease. There are two types of esophageal cancer commonly seen. Esophageal squamous cell carcinoma (ESCC) is the predominant one, accounting for 90–95% of all cases of esophageal cancer. It occurs in the squamous cell lining of the middle section of the esophagus and is more often found in Asia and Africa. China alone is responsible for more than 50% of the patient population. Esophageal adenocarcinoma (EAC), on the other hand, takes place in the cuboidal cells of the esophageal glands near the gastroesophageal junction and has been

growing rapidly in western countries in recent years. We start this section with an overall commentary, written by Romanian scholars, on current treatment options for esophageal cancer, including chemotherapy, radiotherapy, resection surgery, and minimally invasive approach, followed by two chapters, contributed by Dr. Calduch et al. (Hospital Clinic Uni‐ versity of Valencia, Spain) and Dr. Buruzovic et al. (Harvard Medical School, USA), which go into more details about minimally invasive surgery and radiotherapy, respectively. There is a bundle of evidence showing that minimally invasive surgery is a more favorable ap‐ proach to treat cancer in contrast to open surgery, and a combination of external beam radia‐ tion therapy and moderate-dose rate brachytherapy can achieve a better outcome.

The progress of esophageal cancer is staged based on metastasis, i.e., how far the cancer cells have invaded into the esophageal wall or other organs, how many lymph nodes are affect‐ ed, etc. Chapter 5, written by Dr. Makino et al. (Nippon Medical School, Japan), demon‐ strates how lymph node dissection is performed as a part of the treatment for esophageal cancer. They explain the technical differences in ESCC versus EAC so clearly that a profes‐ sional reader would not have much difficulty to perform the surgery on his own just using the chapter as a reference.

Because of the critical location of the esophagus, any abnormalities associated with this or‐ gan can seriously obstruct food uptake and thereby impair the nutritional balance of the in‐ dividual. For esophageal cancer patients, this is particularly devastating because either chemo-radiotherapy or surgical treatment can cause severe damage to the already problem‐ atic organ. Chapter 6 from Dr. Schizas and his associates (National and Kapodistrian Uni‐ versity of Athens, Greece) has a long discussion on this topic and provides clear guidelines for nutritional management in different situations, including dietary counseling, oral sup‐ plementation, tube feeding, and combination of all.

Besides cancer, the other common abnormalities associated with the esophagus include esophagitis, varices,constrictions, motility disorders, as well as congenital diseases like atre‐ sia, trachea-esophageal fistula, achalasia, and diverticula. In the next chapter, Dr. Hossein‐ pour and Dr. Ahmadi (Isfahan University of Medical Sciences, Iran) present a full description on these birth defects, based on their years of experience in the pediatric world. Esophageal atresia refers to the situations in which esophageal tube closes itself before reaching the stomach. So, whatever eaten or drunk cannot get into the rest of the digestive system. It happens in 1 in about 2500 newborns. Trachea-esophageal fistula, on the other hand, refers to a condition in which the esophageal tube accidentally hooks up with the tra‐ chea; as a result, whatever eaten or drunk goes into the respiratory system. These two events could take place together or separately. The common treatment is surgically separating the esophagus from the trachea and reconnecting the esophagus to the stomach. Esophageal achalasia is not a connection problem, rather a case of muscular malfunction in which the lower esophageal sphincter is constantly closed so that whatever eaten or drunk remains in the esophagus and, consequently, the esophagus becomes massively stretched and acts like a "pseudo-stomach." Besides surgical treatment, agents like calcium channel blockers can be used to relax the sphincter. However, while achalasia is relieved, GERD could step in to take the place because after such medication, the lower sphincter would not be able to hold the stomach acid below the esophagus. Fortunately, this is a rare disease, only happens in 1 per 100,000 people. Esophageal diverticulum occurs in response to inflammation or high inter‐ nal pressure. A protruding pouch forms from the side of the esophageal wall. Surgical treat‐ ment is usually the way of management.

GERD is largely associated with the fast-growing obese/overweight population. The excess fat in the abdominal area puts a constant pressure on the stomach and creates a high frequency of esophageal acid exposure. A recent study showed that global obesity rates have doubled since 1980. It is predicted that by the year 2020, 77.6% of American men and 71.1% of American women will be overweight. A similar trend is also seen in China, the most populated state. According to the statistics in 2013, at least 46 million of Chinese adults were suffering from obesity, and another 300 million were considered as overweight. Current GERD treatment primarily relies on acid-suppressive medications (i.e., proton pump inhibitors or PPI) and repair surgery, but neither is a clear winner thus far. In fact, increasing evidence shows multi‐ ple side effects associated with this line of drugs, such as decreased absorption of vitamins/ minerals, susceptibility to infections, bone fracture, and even elevated risk of developing can‐ cer. For these reasons, the Food and Drug Administration of the United States has repeatedly issued warnings on the use of PPI. For people who have responded to medication but contin‐ ue to experience GERD symptoms, surgery to reconstruct the esophageal sphincter is usually an option. However, only 5% of GERD patients undergo surgery, and follow-up study found that almost two-thirds of the surgery patients were back on medication. In Chapter 8, Tunisi‐ an scholars present a retrospective study on PPI use in elderly people, raising alert on these drugs despite their effectiveness in control of GERD symptoms.

growing rapidly in western countries in recent years. We start this section with an overall commentary, written by Romanian scholars, on current treatment options for esophageal cancer, including chemotherapy, radiotherapy, resection surgery, and minimally invasive approach, followed by two chapters, contributed by Dr. Calduch et al. (Hospital Clinic Uni‐ versity of Valencia, Spain) and Dr. Buruzovic et al. (Harvard Medical School, USA), which go into more details about minimally invasive surgery and radiotherapy, respectively. There is a bundle of evidence showing that minimally invasive surgery is a more favorable ap‐ proach to treat cancer in contrast to open surgery, and a combination of external beam radia‐

The progress of esophageal cancer is staged based on metastasis, i.e., how far the cancer cells have invaded into the esophageal wall or other organs, how many lymph nodes are affect‐ ed, etc. Chapter 5, written by Dr. Makino et al. (Nippon Medical School, Japan), demon‐ strates how lymph node dissection is performed as a part of the treatment for esophageal cancer. They explain the technical differences in ESCC versus EAC so clearly that a profes‐ sional reader would not have much difficulty to perform the surgery on his own just using

Because of the critical location of the esophagus, any abnormalities associated with this or‐ gan can seriously obstruct food uptake and thereby impair the nutritional balance of the in‐ dividual. For esophageal cancer patients, this is particularly devastating because either chemo-radiotherapy or surgical treatment can cause severe damage to the already problem‐ atic organ. Chapter 6 from Dr. Schizas and his associates (National and Kapodistrian Uni‐ versity of Athens, Greece) has a long discussion on this topic and provides clear guidelines for nutritional management in different situations, including dietary counseling, oral sup‐

Besides cancer, the other common abnormalities associated with the esophagus include esophagitis, varices,constrictions, motility disorders, as well as congenital diseases like atre‐ sia, trachea-esophageal fistula, achalasia, and diverticula. In the next chapter, Dr. Hossein‐ pour and Dr. Ahmadi (Isfahan University of Medical Sciences, Iran) present a full description on these birth defects, based on their years of experience in the pediatric world. Esophageal atresia refers to the situations in which esophageal tube closes itself before reaching the stomach. So, whatever eaten or drunk cannot get into the rest of the digestive system. It happens in 1 in about 2500 newborns. Trachea-esophageal fistula, on the other hand, refers to a condition in which the esophageal tube accidentally hooks up with the tra‐ chea; as a result, whatever eaten or drunk goes into the respiratory system. These two events could take place together or separately. The common treatment is surgically separating the esophagus from the trachea and reconnecting the esophagus to the stomach. Esophageal achalasia is not a connection problem, rather a case of muscular malfunction in which the lower esophageal sphincter is constantly closed so that whatever eaten or drunk remains in the esophagus and, consequently, the esophagus becomes massively stretched and acts like a "pseudo-stomach." Besides surgical treatment, agents like calcium channel blockers can be used to relax the sphincter. However, while achalasia is relieved, GERD could step in to take the place because after such medication, the lower sphincter would not be able to hold the stomach acid below the esophagus. Fortunately, this is a rare disease, only happens in 1 per 100,000 people. Esophageal diverticulum occurs in response to inflammation or high inter‐ nal pressure. A protruding pouch forms from the side of the esophageal wall. Surgical treat‐

tion therapy and moderate-dose rate brachytherapy can achieve a better outcome.

the chapter as a reference.

VIII Preface

plementation, tube feeding, and combination of all.

ment is usually the way of management.

There is an old Chinese saying, "All diseases come from the mouth." In modern civilization, this may not be absolutely true, but it tells how important eating/drinking is to our health. The next chapter (Larrosa-Haro and Sanchez-Ramirez, Mexico) has a discussion on the issue of caustic ingestion in underaged population. In developing and underdeveloped countries, this happens more often than we think, and it demands attention from both parents and the health professionals. Finally, we close this section with a rare topic called lymphocytic esophagitis, contributed by Dr. Daoud and Dr. Bouin (University of Montreal, Canada), which is not yet considered as a disease because the esophagus looks perfectly normal un‐ der the endoscope. However, patients experience discomfort in the chest as well as dyspha‐ gia, and histological examination reveals accumulation of peripapillary lymphocytic infiltrate within esophageal mucosa. Although "it is a condition in search of a disease" at this point, this topic demands a more vigorous study.

The human body is like a machine, and when it has a problem, health professionals like en‐ gineers will step in to fix it. However, all living organisms, including humans, age, and vari‐ ous diseases and other incidences will consume our bodies till a point where they are unrepairable, and then we die. This has made a lot of people think of alternatives. Some engineers with adequate knowledge of bioscience started to think of a possibility of using nonbiological materials to replace those sick or unrepairable organs. Then a new discipline was born, i.e., tissue engineering. In our last chapter of the book, professor Zhu and his team (Ningbo University, China) introduce some recent progress in this field, particularly about esophageal engineering. It is exciting to learn that in the near future, we could have some parts in our body that can never get sick.

> **Jianyuan Chai, PhD** University of California, USA Baotou Medical College, China
