Diagnostic Atlas of Gastroesophageal Reflux Disease -  Parakrama T. Chandrasoma

Diagnostic Atlas of Gastroesophageal Reflux Disease (eBook)

A New Histology-based Method
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2011 | 1. Auflage
320 Seiten
Elsevier Science (Verlag)
978-0-08-087803-4 (ISBN)
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159,89 inkl. MwSt
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Gastroesophageal reflux is one of the most common maladies of mankind. Approximately 40% of the adult population of the USA suffers from significant heartburn and the numerous antacids advertised incessantly on national television represents a $8 billion per year drug market. The ability to control acid secretion with the increasingly effective acid-suppressive agents such as the H2 blockers (pepcid, zantac) and proton pump inhibitors (nexium, prevacid) has given physicians an excellent method of treating the symptoms of acid reflux.

Unfortunately, this has not eradicated reflux disease. It has just changed its nature. While heartburn, ulceration and strictures have become rare, reflux-induced adenocarcinoma of the esophagus is becoming increasingly common. Adenocarcinoma of the esophagus and gastric cardia is now the most rapidly increasing cancer type in the Western world.

At present, there is no histologic test that has any practical value in the diagnosis of reflux disease. The only histologic diagnostic criteria are related to changes in the squamous epithelium which are too insensitive and nonspecific for effective patient management. It is widely recognized that columnar metaplasia of the esophagus (manifest histologically as cardiac, oxyntocardiac and intestinal epithelia) is caused by reflux. However, except for intestinal metaplasia, which is diagnostic for Barrett esophagus, these columnar epithelia are not used to diagnose reflux disease in biopsies. The reason for this is that these epithelial types are indistinguishable from normal gastric cardiac mucosa. In standard histology texts, this normal gastric cardia is 2-3 cm long.

In the mid-1990s, Dr. Chandrasoma and his team at USC produced autopsy data suggesting that cardiac and oxyntocardiac mucosa is normally absent from this region and that their presence in biopsies was histologic evidence of reflux disease. From this data, they determined that the presence of cardiac mucosa was a pathologic entity caused by reflux and could therefore be used as a highly specific and sensitive diagnostic criterion for the histologic diagnosis of reflux disease. They call this entity reflux carditis. In addition, the length of these metaplastic columnar epithelia in the esophagus was an accurate measure of the severity of reflux disease in a given patient.

At present, there is some controversy over whether cardiac mucosa is totally absent or present normally to the extent of 0-4 mm. While this should not be a deterrent to changing criteria which are dependent on there normally being 20-30 cm of cardiac mucosa, there has been little mainstream attempt to change existing endoscopic and pathologic diagnostic criteria in the mainstream of either gastroenterology or pathology.

The ATLAS will be the source of easily digestible practical information for pathologists faced with biopsies from this region. It will also guide gastroenterologists as they biopsy these patients.

* The American Gastroenterological Association claims there are 14,500 members worldwide who are practicing physicians and scientists who research, diagnose and treat disorders of the gastrointestinal tract and liver
* According to the American Society for Clinical Pathology, there are 12,000 board certified pathologists in the U.S.
* Adenocarcinoma of the esophagus and gastric cardia is now the most rapidly increasing cancer type in the Western world
* Approximately 40% of the adult population of the U.S. suffers from significant heartburn and the numerous antacids advertised on national television represents an $8 billion per year drug market
Gastroesophageal reflux is one of the most common maladies of mankind. Approximately 40% of the adult population of the USA suffers from significant heartburn and the numerous antacids advertised incessantly on national television represents a $8 billion per year drug market. The ability to control acid secretion with the increasingly effective acid-suppressive agents such as the H2 blockers (pepcid, zantac) and proton pump inhibitors (nexium, prevacid) has given physicians an excellent method of treating the symptoms of acid reflux.Unfortunately, this has not eradicated reflux disease. It has just changed its nature. While heartburn, ulceration and strictures have become rare, reflux-induced adenocarcinoma of the esophagus is becoming increasingly common. Adenocarcinoma of the esophagus and gastric cardia is now the most rapidly increasing cancer type in the Western world.At present, there is no histologic test that has any practical value in the diagnosis of reflux disease. The only histologic diagnostic criteria are related to changes in the squamous epithelium which are too insensitive and nonspecific for effective patient management. It is widely recognized that columnar metaplasia of the esophagus (manifest histologically as cardiac, oxyntocardiac and intestinal epithelia) is caused by reflux. However, except for intestinal metaplasia, which is diagnostic for Barrett esophagus, these columnar epithelia are not used to diagnose reflux disease in biopsies. The reason for this is that these epithelial types are indistinguishable from "e;normal"e; "e;gastric"e; cardiac mucosa. In standard histology texts, this "e;normal gastric cardia"e; is 2-3 cm long.In the mid-1990s, Dr. Chandrasoma and his team at USC produced autopsy data suggesting that cardiac and oxyntocardiac mucosa is normally absent from this region and that their presence in biopsies was histologic evidence of reflux disease. From this data, they determined that the presence of cardiac mucosa was a pathologic entity caused by reflux and could therefore be used as a highly specific and sensitive diagnostic criterion for the histologic diagnosis of reflux disease. They call this entity "e;reflux carditis"e;. In addition, the length of these metaplastic columnar epithelia in the esophagus was an accurate measure of the severity of reflux disease in a given patient.At present, there is some controversy over whether cardiac mucosa is totally absent or present normally to the extent of 0-4 mm. While this should not be a deterrent to changing criteria which are dependent on there normally being 20-30 cm of cardiac mucosa, there has been little mainstream attempt to change existing endoscopic and pathologic diagnostic criteria in the mainstream of either gastroenterology or pathology. The ATLAS will be the source of easily digestible practical information for pathologists faced with biopsies from this region. It will also guide gastroenterologists as they biopsy these patients. - The American Gastroenterological Association claims there are 14,500 members worldwide who are practicing physicians and scientists who research, diagnose and treat disorders of the gastrointestinal tract and liver- According to the American Society for Clinical Pathology, there are 12,000 board certified pathologists in the U.S. - Adenocarcinoma of the esophagus and gastric cardia is now the most rapidly increasing cancer type in the Western world- Approximately 40% of the adult population of the U.S. suffers from significant heartburn and the numerous antacids advertised on national television represents an $8 billion per year drug market

Cover 1
About the Author 8
Other Publications by the Author 10
Table of contents 12
CHAPTER 1: Reflux-Induced Cancer: An Epidemic We Need to Address Now 18
Epidemiology of Reflux-Induced Cancer 19
The Problem 23
The Reflux-to-Adenocarcinoma Sequence 27
The Future Without Change 36
Can Reflux-Induced Adenocarcinoma Be Prevented? 39
Objections to Anti-Reflux Surgery 43
A Plea for an Aggressive Approach 44
Expectation of Change 51
REFERENCES 51
CHAPTER 2: The Present State of Diagnosis of Reflux Disease 53
Presently Used Diagnostic Criteria of Reflux Disease 53
Columnar-Lined Esophagus: An Inexplicably Ignored Diagnostic Criterion for Reflux Disease 69
REFERENCES 76
CHAPTER 3: Histologic Definition and Diagnosis of Epithelial Types in the Esophagus and Stomach 78
The Importance of Histology in Understanding Disease 78
Embryologic Development 78
Histologic Definition of Epithelial Types in Postnatal Esophagus and Proximal Stomach 82
Diagnosis of Columnar Epithelial Types 98
CASE STUDY 106
Application of Histologic Definitions 109
Problems in Differential Diagnosis Between Columnar Epithelial Types 110
CASE STUDY 120
CASE STUDY 126
REFERENCES 128
CHAPTER 4: Definition of Normal and Reflux-Induced Anatomy and Histology 129
Normal Anatomy 129
Normal Histology of the Esophagus and Proximal Stomach 136
Definition of the Gastroesophageal Junction 140
Pathogenesis of Reflux Disease 149
The Mechanism of Gastroesophageal Reflux 150
Anatomic Location and Significance of Epithelial Types: Resolution of Controversy 158
New Definitions of the Normal State and Gastroesophageal Reflux Disease 171
REFERENCES 171
CHAPTER 5: Cellular Changes of Non-Neoplastic Gastroesophageal Reflux Disease 174
Squamous Epithelial Injury 175
Sequence of Columnar Metaplasia of the Esophagus 175
Distribution of Columnar Epithelial Types 182
Relationship Between Prevalence of Intestinal Metaplasia and Length of Columnar-Lined Esophagus 183
Historical Differences in Epithelial Composition of Columnar-Lined Esophagus 185
Mechanism of the Genetic Switches in Columnar-Lined Esophagus 187
CASE STUDY 193
Reversibility of Genetic Switches 196
Barrett Esophagus: Five Decades of Medical Failure 197
REFERENCES 199
CHAPTER 6: Reflux-Induced Adenocarcinoma of the Esophagus 201
CASE STUDY 201
The Target Cell 206
The Carcinogen 207
CASE STUDY 208
Interaction Between Carcinogens and Target Cells 213
CASE STUDY 215
Factors Associated with an Increased Cancer Risk in Gastroesophageal Reflux Disease 218
Factors that Are Protective Against Development of Cancer in Barrett Esophagus 224
Assessment of Cancer Risk in Barrett Esophagus 227
Prevalent Cancer in Barrett Esophagus 242
Conclusion 246
REFERENCES 246
CHAPTER 7: New Histology-Based Definitions and Method of Diagnosis of Reflux Disease 249
A New Histologic Definition of Gastroesophageal Reflux Disease 249
Reflux Carditis: The Perfect Definition of Gastroesophageal Reflux Disease 253
A New Definition of Barrett Esophagus 259
CASE STUDY 262
A New Diagnostic Method for Reflux Disease 266
CASE STUDY 281
CASE STUDY 301
REFERENCES 306
Index 308

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