GERD: A New Understanding of Pathology, Pathophysiology, and Treatment transforms the assessment of gastroesophageal reflux disease (GERD) from its present state, which is largely dependent on clinical definition and management, to a more objective scientific basis that depends on pathologic assessment. Sequential chapters in this single-author book describe the fetal development of the esophagus, the normal adult state, and the way exposure to gastric juice causes epithelial and lower esophageal sphincter damage at a cellular level. It allows recognition of the pathologic manifestations of lower esophageal sphincter damage and develops new histopathologic criteria for quantitating such damage. This understanding provides new pathologic criteria for definition and diagnosis of GERD from its earliest cellular stage. Algorithms based on measurement of sphincter damage can identify, even before the onset of clinical GERD, persons who will never develop GERD during life, those who develop GERD but remain with mild and easily controlled disease, and those who will progress to severe GERD with failure to control symptoms, Barrett esophagus and adenocarcinoma. Aggressive early intervention in the last group with the objective of preventing disease progression to its end points of uncontrolled symptoms and adenocarcinoma becomes feasible.
1. Introduction: Discovery: A Path to a New Solution for Gastroesophageal Reflux Disease - p. xvii 2. Chapter 1. Definition of Gastroesophageal Reflux Disease: Past, Present, and Future - p. 1 3. Chapter 2. Present Diagnosis and Management of Gastroesophageal Reflux Disease: The Good, Bad, and Ugly - p. 25 4. Chapter 3. Fetal and Postnatal Development of the Esophagus and Proximal Stomach - p. 59 5. Chapter 4. Histologic Definition and Diagnosis of Epithelia in the Esophagus and Proximal Stomach - p. 73 6. Chapter 5. Definition of the Normal State—A Yet Unfinished Saga - p. 109 7. 1. Normal Cardiac Epithelium: A Myth Resulting in a Presently Held False Dogma - p. 110 8. 2. Eradication of the Myth That Cardiac Epithelium Normally Lines the Proximal Stomach - p. 114 9. 3. Study of the Region Distal to the Endoscopic Gastroesophageal Junction in Resected Specimens - p. 126 10. 4. Endoscopic Biopsy in Asymptomatic Volunteers - p. 129 11. 5. Endoscopic Biopsy Studies in Clinical Patients - p. 132 12. 6. Multilevel Endoscopic Biopsies Distal to the Endoscopic Gastroesophageal Junction - p. 135 13. 7. What Is the Significance of Cardiac Epithelium Distal to the Endoscopic Gastroesophageal Junction? - p. 135 14. 8. Reviews of the Meaning of Cardiac Epithelium Distal to the Endoscopic Gastroesophageal Junction - p. 140 15. 9. Does Cardiac Epithelium Have Features of Columnar-Lined Esophagus or Gastric Epithelium? - p. 141 16. 10. Relationship of Cardiac Epithelium to Gastroesophageal Reflux Disease and Gastritis - p. 145 17. 11. Relationship of Cardiac Epithelium to Visible Columnar-Lined Esophagus - p. 146 18. 12. Conclusion - p. 148 19. Chapter 6. Definition of the Gastroesophageal Junction - p. 153 20. Chapter 7. The Normal Lower Esophageal Sphincter - p. 183 21. Chapter 8. The Pathogenesis of Early GERD - p. 199 22. Chapter 9. Correlation of LES Damage and GERD - p. 231 23. Chapter 10. The Effect of Damage to the Abdominal Segment of the LES: The Dilated Distal Esophagus - p. 255 24. 1. Definition of the Dilated Distal Esophagus - p. 260 25. 2. Pathogenesis of the Dilated Distal Esophagus - p. 261 26. 3. Variation in Length of the Dilated Distal Esophagus - p. 261 27. 4. Mathematical Formulae to Define the Normal and Abnormal States - p. 263 28. 5. Anatomical Changes Associated With Abdominal Lower Esophageal Sphincter Damage - p. 264 29. 6. Clinical Syndromes Associated With the Dilated Distal Esophagus - p. 278 30. 7. Histologic Composition of the Dilated Distal Esophagus - p. 281 31. 8. Relationship Between the Dilated Distal Esophagus and Visible Columnar-Lined Esophagus - p. 290 32. Chapter 11. Columnar-Lined Esophagus (Microscopic and Visible) and Barrett Esophagus - p. 297 33. 1. The Past: Historical Evolution of Columnar-Lined Esophagus - p. 300 34. 2. The Present State of the Art - p. 314 35. 3. The Future: The Complete Understanding of Columnar-Lined Esophagus - p. 318 36. 4. Prevalence of Columnar-Lined Esophagus - p. 321 37. 5. Clinical Manifestations of Columnar-Lined Esophagus - p. 326 38. 6. Histology of Columnar-Lined Esophagus - p. 326 39. 7. The Detection of Intestinal Metaplasia in Columnar-Lined Esophagus by Endoscopic Biopsy - p. 329 40. 8. The Distribution of Epithelial Types in Visible Columnar-Lined Esophagus - p. 334 41. 9. Difference in the Prevalence of Intestinal Metaplasia With Different Length of Visible Columnar-Lined Esophagus - p. 336 42. 10. (Future) Definitions Based on the New Concepts - p. 337 43. 11. Relationship of Columnar-Lined Esophagus to Adenocarcinoma - p. 339 44. Chapter 12. Esophageal Adenocarcinoma - p. 341 45. 1. Does Present Medical Therapy Promote Esophageal Adenocarcinoma? - p. 341 46. 2. Should Adenocarcinoma Be Included in the Definition of Gastroesophageal Reflux Disease? - p. 348 47. 3. The Changing Definition of Esophageal Adenocarcinoma - p. 349 48. 4. Epidemiology of Esophageal Adenocarcinoma - p. 359 49. 5. Proposed New Terminology for Esophageal Adenocarcinoma - p. 362 50. 6. The Window of Opportunity for Preventing Esophageal Adenocarcinoma - p. 367 51. 7. Target Epithelium for Carcinogenesis: Intestinal Metaplasia - p. 370 52. 8. Increased Risk for Carcinogenesis: Decision for Surveillance - p. 376 53. 9. Risk Indicators for Esophageal Adenocarcinoma - p. 379 54. Chapter 13. Progression of GERD at the Clinical Level - p. 391 55. Chapter 14. Progression of GERD at a Pathological Level - p. 417 56. Chapter 15. Molecular Evolution of Esophageal Epithelial Metaplasia - p. 457 57. Chapter 16. Progression of GERD From the Perspective of LES Damage - p. 479 58. Chapter 17. New Pathologic Test of LES Damage - p. 503 59. Chapter 18. New Method of Functional Assessment of the LES - p. 527 60. Chapter 19. Prediction of Future Progression of LES Damage - p. 541 61. Chapter 20. Proof of Concept of the New Diagnostic Method - p. 559 62. Chapter 21. Application of the New Method to Present and Future Management of GERD - p. 583 63. Author Index - p. 601 64. Subject Index - p. 609
GERD: A New Understanding of Pathology, Pathophysiology, and Treatment transforms the assessment of gastroesophageal reflux disease (GERD) from its present state, which is largely dependent on clinical definition and management, to a more objective scientific basis that depends on pathologic assessment. Sequential chapters in this single-author book describe the fetal development of the esophagus, the normal adult state, and the way exposure to gastric juice causes epithelial and lower esophageal sphincter damage at a cellular level. It allows recognition of the pathologic manifestations of lower esophageal sphincter damage and develops new histopathologic criteria for quantitating such damage. This understanding provides new pathologic criteria for definition and diagnosis of GERD from its earliest cellular stage. Algorithms based on measurement of sphincter damage can identify, even before the onset of clinical GERD, persons who will never develop GERD during life, those who develop GERD but remain with mild and easily controlled disease, and those who will progress to severe GERD with failure to control symptoms, Barrett esophagus and adenocarcinoma. Aggressive early intervention in the last group with the objective of preventing disease progression to its end points of uncontrolled symptoms and adenocarcinoma becomes feasible.
1. Introduction: Discovery: A Path to a New Solution for Gastroesophageal Reflux Disease - p. xvii 2. Chapter 1. Definition of Gastroesophageal Reflux Disease: Past, Present, and Future - p. 1 3. Chapter 2. Present Diagnosis and Management of Gastroesophageal Reflux Disease: The Good, Bad, and Ugly - p. 25 4. Chapter 3. Fetal and Postnatal Development of the Esophagus and Proximal Stomach - p. 59 5. Chapter 4. Histologic Definition and Diagnosis of Epithelia in the Esophagus and Proximal Stomach - p. 73 6. Chapter 5. Definition of the Normal State—A Yet Unfinished Saga - p. 109 7. 1. Normal Cardiac Epithelium: A Myth Resulting in a Presently Held False Dogma - p. 110 8. 2. Eradication of the Myth That Cardiac Epithelium Normally Lines the Proximal Stomach - p. 114 9. 3. Study of the Region Distal to the Endoscopic Gastroesophageal Junction in Resected Specimens - p. 126 10. 4. Endoscopic Biopsy in Asymptomatic Volunteers - p. 129 11. 5. Endoscopic Biopsy Studies in Clinical Patients - p. 132 12. 6. Multilevel Endoscopic Biopsies Distal to the Endoscopic Gastroesophageal Junction - p. 135 13. 7. What Is the Significance of Cardiac Epithelium Distal to the Endoscopic Gastroesophageal Junction? - p. 135 14. 8. Reviews of the Meaning of Cardiac Epithelium Distal to the Endoscopic Gastroesophageal Junction - p. 140 15. 9. Does Cardiac Epithelium Have Features of Columnar-Lined Esophagus or Gastric Epithelium? - p. 141 16. 10. Relationship of Cardiac Epithelium to Gastroesophageal Reflux Disease and Gastritis - p. 145 17. 11. Relationship of Cardiac Epithelium to Visible Columnar-Lined Esophagus - p. 146 18. 12. Conclusion - p. 148 19. Chapter 6. Definition of the Gastroesophageal Junction - p. 153 20. Chapter 7. The Normal Lower Esophageal Sphincter - p. 183 21. Chapter 8. The Pathogenesis of Early GERD - p. 199 22. Chapter 9. Correlation of LES Damage and GERD - p. 231 23. Chapter 10. The Effect of Damage to the Abdominal Segment of the LES: The Dilated Distal Esophagus - p. 255 24. 1. Definition of the Dilated Distal Esophagus - p. 260 25. 2. Pathogenesis of the Dilated Distal Esophagus - p. 261 26. 3. Variation in Length of the Dilated Distal Esophagus - p. 261 27. 4. Mathematical Formulae to Define the Normal and Abnormal States - p. 263 28. 5. Anatomical Changes Associated With Abdominal Lower Esophageal Sphincter Damage - p. 264 29. 6. Clinical Syndromes Associated With the Dilated Distal Esophagus - p. 278 30. 7. Histologic Composition of the Dilated Distal Esophagus - p. 281 31. 8. Relationship Between the Dilated Distal Esophagus and Visible Columnar-Lined Esophagus - p. 290 32. Chapter 11. Columnar-Lined Esophagus (Microscopic and Visible) and Barrett Esophagus - p. 297 33. 1. The Past: Historical Evolution of Columnar-Lined Esophagus - p. 300 34. 2. The Present State of the Art - p. 314 35. 3. The Future: The Complete Understanding of Columnar-Lined Esophagus - p. 318 36. 4. Prevalence of Columnar-Lined Esophagus - p. 321 37. 5. Clinical Manifestations of Columnar-Lined Esophagus - p. 326 38. 6. Histology of Columnar-Lined Esophagus - p. 326 39. 7. The Detection of Intestinal Metaplasia in Columnar-Lined Esophagus by Endoscopic Biopsy - p. 329 40. 8. The Distribution of Epithelial Types in Visible Columnar-Lined Esophagus - p. 334 41. 9. Difference in the Prevalence of Intestinal Metaplasia With Different Length of Visible Columnar-Lined Esophagus - p. 336 42. 10. (Future) Definitions Based on the New Concepts - p. 337 43. 11. Relationship of Columnar-Lined Esophagus to Adenocarcinoma - p. 339 44. Chapter 12. Esophageal Adenocarcinoma - p. 341 45. 1. Does Present Medical Therapy Promote Esophageal Adenocarcinoma? - p. 341 46. 2. Should Adenocarcinoma Be Included in the Definition of Gastroesophageal Reflux Disease? - p. 348 47. 3. The Changing Definition of Esophageal Adenocarcinoma - p. 349 48. 4. Epidemiology of Esophageal Adenocarcinoma - p. 359 49. 5. Proposed New Terminology for Esophageal Adenocarcinoma - p. 362 50. 6. The Window of Opportunity for Preventing Esophageal Adenocarcinoma - p. 367 51. 7. Target Epithelium for Carcinogenesis: Intestinal Metaplasia - p. 370 52. 8. Increased Risk for Carcinogenesis: Decision for Surveillance - p. 376 53. 9. Risk Indicators for Esophageal Adenocarcinoma - p. 379 54. Chapter 13. Progression of GERD at the Clinical Level - p. 391 55. Chapter 14. Progression of GERD at a Pathological Level - p. 417 56. Chapter 15. Molecular Evolution of Esophageal Epithelial Metaplasia - p. 457 57. Chapter 16. Progression of GERD From the Perspective of LES Damage - p. 479 58. Chapter 17. New Pathologic Test of LES Damage - p. 503 59. Chapter 18. New Method of Functional Assessment of the LES - p. 527 60. Chapter 19. Prediction of Future Progression of LES Damage - p. 541 61. Chapter 20. Proof of Concept of the New Diagnostic Method - p. 559 62. Chapter 21. Application of the New Method to Present and Future Management of GERD - p. 583 63. Author Index - p. 601 64. Subject Index - p. 609
