1. DISEASES OF THE ESOPHAGUS
Prof. Ferenc Szalay MD, PhD
1st Department of Medicine of Semmelweis University Budapest, Hungary
Budapest, lecture for students

2. Diseases of the esophagus
GERD Motility disorders Esophagitis (infection, chemicals, pills) Neurological disorders Skeletal muscle disorders Varices Mallory-Weiss sy. Barrett’s Tumors
Common complains Wide range of symptoms

3. Swallowing
Many muscle 5 nerves : V, VII, IX, X, XII Stages oral voluntary pharyngeal involuntary esophageal LES relaxed 1 second 5 steps

4. 5 steps within 1 second
1. Soft palate is elevated + retracted to prevent nasopharingeal reflux 2. Vocal cords are closed Epiglottis swings backward  closure the larynx 3. UES relaxes 4. Larynx is pulled upward streching, opening E and UES 5. Contractions of pharyngeal muscle

5. Anatomy

6. Anatomy

8. Motility disorders of oropharynx
Dysfunction of the UES
Zenker’s diverticulum, Cricopharingeal bar
Neurologic disorders (stroke)
Cerebrovascular diseases, Poliomyelitis
Amyotrophic lateral sclerosis, Multiple sclerosis, Brain stem tumor
Skeletal musclular disorders
Myastenia gravis, Metabolic myopathy (T4 toxicosis, myxedema, steroid)
Muscular dystrophies
Local structural lesions
Neoplasms, extinsic compression (Thyroid, cervical spur), Surgery
Common problem in the elderly patients and frequently associated with poor prognosis owing to a high incidence of aspiration

9. Zenker’s diverticulum

10. Motility disorders of the esophagus
 Smooth muscle diseases (scleroderma)  Intrinsic nervous system Achalasia, Chagas disease  loss of ganglion cells in Auerbach plexus  LES   no peristalsis Diffuse esophagus spasm and its variants

11. Esophagus motility disorder: scleroderma

12. Achalasia: Chagas’ disease
Cause:
Tripanosoma Cruzi inf.

13. Diffuse esophageal spasms

14. Rings and Webs
Schatzki’s ring - proximal or distal - congenital or secondary to GERD Plummer Vinson syndrome - upper E web - dysphagia - irondeficiency anemia Symptoms if diameter < 13 mm - intermittent dysphagia for solid food - sudden: “steak house syndrome” Treatment - mechanical dilators

15. Schatzki’s ring

16. Endoscopic image of the narrow area in mid-esophagus

17. Post-mortem specimen from a similar case of esophageal narrowing in a young boxer.

18. Map of lymph nodes near the oesophagus

19. Radiographic evaluation in suspected esophageal cancer

20. Gastroesophageal junction type II tumors

21. Esophageal cancer

23. AJCC Staging of Esophagus: TNM Staging
Regional lymph nodes (N)
Nx Regional lymph nodes cannot be assassed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
Distant metastasis (M)
Mx Distant metastasis cannot be assassed
M0 No distant metastasis
M1 Distant metastasis
Tumors of lower or upper esophagus
M1a Metastasis in nonregional lymph node
M1b Distant metastasis (eg: liver, bone, brain)
Tumors of middle esophagus
M1a Not applicable
M1b Metastasis in nonregional lymph node or distant metastasis (eg: liver, bone, brain)

24. AJCC Staging of Esophagus: TNM Staging
Stage Tumor Node Metastasis
Stage 0 Tis N0 M0
Stage I T1 N0 M0
T2 N0 M0
Stage IIA T3 N0 M0
T1 N1 M0
Stage IIB T2 N1 M0
T3 N1 M0
Stage III T4 Any N M0
Stage IV Any T Any N M1
Stage IV A Any T Any N M1a
Stage IV B Any T Any N M1b

25. Resected esophageal specimen

26. Other esophageal disorders

27. Coin in upper oesophagus

28. INFECTIONS OF THE OESOPHAGUS
Viral herpes, CMV
Fungal Candida
Most common in immuncompromized patients:
AIDS
Immunosuppressive treatment
Immune defects
Antibiotic os steroid treatment

29. Candida oesophagitis

30. Acid-related
diseases of the
oesophagus
GERD / GORD

31. Definitions Heartburn: Oesophagitis:
Burning retrosternal pain radiating upward due to exposure of the oesophagus to acid
Oesophagitis:
Endoscopically demonstrated damage to the oesophageal mucosa
Gastro-oesophageal reflux disease (GORD):
Pathological reflux ranges from simple to erosive to Barrett’s
Non-erosive reflux disease (NERD):
Reflux disease in which erosion does not occur
The primary symptom of acid-related diseases of the oesophagus is heartburn. The pain of heartburn can be severe and frightening for the patient. It can mimic the pain of a heart attack, so it is important to take seriously any symptoms with sudden onset.
On examination, many patients with heartburn have oesophagitis – inflammation of the oesophagus that can be seen on endoscopy.
Gastro-oesophageal reflux disease (GORD) is the pathological mechanism by which acid arrives in the oesophagus to cause inflammation/erosion of the oesophageal mucosa.
Many patients with GORD do not have evidence of oesophagitis and are classified as having non-erosive or negative-endoscopy reflux disease (NERD).
Barrett’s oesophagus is a pre-cancerous lesion.
Throughout this presentation, GORD is equivalent to gastro-esophageal reflux disease, GERD.
Talley et al., BMJ 2001; 323: 1294–7.
de Caestecker, BMJ 2001; 323: 736–9.
Nathoo, Int J Clin Pract 2001; 55: 465–9.
Quigley, Eur J Gastroenterol Hepatol 2001; 13(Suppl 1): S13–18.

32. Pathophysiology of GORD
salivary HCO3
Impaired mucosal defence
oesophageal clearance of acid
(lying flat, alcohol, coffee)
Impaired LOS (smoking, fat, alcohol)
– transient LOS relaxations
– basal tone
Hiatus hernia
acid output
(smoking, coffee)
H+ Pepsin
Bile and pancreatic enzymes
There are several possible mechanisms that can account for increased gastro-oesophageal reflux. These include:
reduced salivary bicarbonate impairs neutralisation of gastric acid (may be caused by reduced secretion or impaired peristalsis and reduced saliva transport)
impaired mucosal defence/acid clearance in the oesophagus (normal peristaltic activity in the oesophagus causes acid to be cleared back into the stomach – lying flat and agents such as alcohol and caffeine impair this mechanism
increased reflux of acid from the stomach due to impaired pressure at the lower oesophageal sphincter, to increased back pressure from the stomach or to delayed gastric emptying (which allows acid to stay longer in the stomach and hence have more opportunity to reflux into the oesophagus).
Many lifestyle factors, such as smoking, alcohol intake, fat intake and obesity can cause GORD.
LOS = lower oesophageal sphincter.
intragastric pressure (obesity, lying flat)
bile reflux
gastric emptying (fat)
de Caestecker, BMJ 2001; 323:736–9.
Johanson, Am J Med 2000; 108(Suppl 4A): S99–103.

33. Diagnosis of GORD History Barium swallow
1. Does reflux exist?
2. Is acid R responsible for symptoms?
3. Has R led to esophagus damage?
Barium swallow
Radionuclide scintigraphy (99mTc sulfur colloid)
E. manometry
Bernstein test
pH monitoring
Endoscopy

34. Bernstein test
Retrosternal pain for
0.1 N HCl

35. Los Angeles classification system for oesophagitis
Grade A
Grade B
One or more mucosal breaks, no longer than 5 mm, that do not extend between the tops of two mucosal folds
One or more mucosal breaks, more than 5 mm long, that do not extend between the tops of two mucosal folds
Grade C
Grade D
One or more mucosal breaks, that are continuous between the tops of two or more mucosal folds, but which involve less than 75% of the circumference
One or more mucosal breaks, that involve at least 75% of the oesophageal circumference
The Los Angeles classification system can be used to describe varying severities of reflux oesophagitis.
The Savary-Miller classification can also be used to classify oesophagitis (see next slide) and is more commonly used in Europe.
Lundell et al., Gut 1999; 45: 172–80.

36. Savary-Miller classification of oesophagitis
Grade I
One or several erosions in one mucosal fold
Grade II
Several erosions in several mucosal folds, the erosions can merge
Grade III
Erosions surrounding the oesophageal circumference
Grade IV
Ulcer(s), strictures, shortening of the oesophagus
Grade V
Barrett’s epithelium
Grade I - V
The Savary-Miller classification system for oesophagitis is most often used in Europe.
Savary & Miller. The Esophagus. In: Handbook & Atlas of Endoscopy. Solothurn, Switzerland: Verlag Gassman AG, 1978: 119–205.

37. Grade I oesophagitis
Savary-Miller classification One or several erosions in one mucosal fold
Reflux oesophagitis grade I.
The most common cause of oesophagitis is gastro-oesophageal reflux.
Of people with GORD, roughly 40% will develop oesophagitis (histologically proven), while 60% will have non-erosive oesophagitis.
The most common symptoms of GORD are heartburn and regurgitation.
The major complications are Barrett's epithelium, stricture, ulceration and bleeding.
Reproduced with permission.
Quigley, Eur J Gastroenterol Hepatol 2001; 13(Suppl 1): S13–18.
Nathoo, Int J Clin Pract 2001; 55: 465–9.

38. Grade II oesophagitis
Savary-Miller classification Several erosions in several mucosal folds, the erosions can merge
Reflux oesophagitis grade II.
Numerous, confluent, erosive, partly fibrin-covered lesions are visible.
The observation that lesions do not cover the whole oesophageal circumference distinguishes this severity of oesophagitis as grade II rather than grade III.
Reproduced with permission.

39. Grade III oesophagitis
Savary-Miller classification Erosions surrounding the oesophageal circumference
Reflux oesophagitis grade III.
Erosive, fibrin-covered lesions affect the whole oesophageal circumference.
Reproduced with permission.
Freytag et al., Atlas of gastrointestinal endoscopy.

40. Savary-Miller classification Ulcer(s), shortening of the oesophagus
Grade IV oesophagitis
Savary-Miller classification Ulcer(s), shortening of the oesophagus
Reflux oesophagitis grade IV.
Severe, haematin covered, ulcerous lesions are observed.
These lesions cause a scarred shortening of the oesophagus (brachyoesophagus).
Other cases show a singular ulcer.
Reproduced with permission.
Freytag et al., Atlas of gastrointestinal endoscopy.

41. Savary-Miller classification Stricture
Grade IV oesophagitis
Savary-Miller classification Stricture
Grade IV oesophagitis.
The oesophageal junction viewed from the distal oesophagus. The opening is not obviously narrowed, but when the scope touched the mucosa, the normal reflex opening did not occur, indicating stricture.
Strictures may be peptic, caustic, post-radiation, inflammatory (non-peptic) including infectious and congenital.
Peptic irritation is a major cause of oesophageal stricture through exposure of the oesophageal epithelium to the caustic effect of gastric acid.
Stricture follows fibrous repair and is more likely to occur when significant necrosis or repeated episodes of oesophagitis have occurred.
Stricture occurs most commonly in the lower third of the oesophagus, often near the gastro-oesophageal junction consistent with its origin in GORD.
Dysphagia is the primary symptom of stricture with a gradual increase in difficulty of swallowing.
Treatment is establishment of an adequate lumen by progressive dilatation of the stricture.
Recurrent dilatation is often necessary.
Treatment of the primary cause of oesophagitis should also be undertaken.
Reproduced with permission.
Nadel, UCHC

42. Savary-Miller classification Moderate Barrett’s oesophagus
Grade V oesophagitis
Savary-Miller classification Moderate Barrett’s oesophagus
Grade V oesophagitis.
Barrett’s mucosa is a metaplastic columnar epithelium that has replaced the native squamous cells at the oesophagocardiac junction. It is thought to provide greater resistance to gastro-oesophageal reflux, which in turn is likely to be the causal agent.
The picture shows dark red, finger-like epithelial islands among areas of normal, non-inflamed, whitish, squamous epithelium.
Only 15% of patients present with GORD-type symptoms.
There is no correlation between the severity of symptoms and the severity grade of the endoscopic findings.
Reproduced with permission.
Freytag et al., Atlas of gastrointestinal endoscopy.

43. Savary-Miller classification Moderate Barrett’s oesophagus
Grade V oesophagitis
Savary-Miller classification Moderate Barrett’s oesophagus
Grade V oesophagitis
Methylene blue staining of a Barrett’s oesophagus.
The normal squamous epithelium is stained only weakly, whereas the columnar Barrett’s epithelium takes up more dye.
Reproduced with permission.
Chromoendoscopic picture
Freytag et al., Atlas of gastrointestinal endoscopy.

44. Columnar cells instead of squamous cells
Barrett’s dysplasia
Columnar cells instead of squamous cells

45. Savary-Miller classification Severe Barrett’s oesophagus
Grade V oesophagitis
Savary-Miller classification Severe Barrett’s oesophagus
Grade V oesophagitis.
In this severe case, all of the squamous epithelium of the lower oesophagus has been replaced by metaplastic Barrett’s epithelium (columnar epithelium).
Reproduced with permission.
Freytag et al., Atlas of gastrointestinal endoscopy.

46. Adenocarcinoma of the oesophagus
Adenocarcinoma of the gastro-oesophageal junction.
The oesophageal mucosa to the left is labelled ‘E’. The gastric mucosa to the right is labelled ‘G’. The arrows point to the heaped up edge of the ulcerated lesion which is the carcinoma (located in the centre of the image).
Most cases of oesophageal adenocarcinoma arise in the lower third of the oesophagus in the setting of pre-existent Barrett's oesophagus secondary to reflux oesophagitis.
Dysphagia and weight loss are the two most common symptoms.
Symptoms of pre-existing reflux are present in less than 50% of patients.
Five-year survival is dismal at less than 15%.
Primary therapy is surgery or chemotherapy with radiation therapy, but chemotherapy and radiation therapy are less effective in adenocarcinoma than in squamous cancer.
Reproduced with permission.
Nadel/Saint Francis Hospital. In: Gastrointestinal Pathology. Fenoglio-Preiser, New York: Raven Press, 1989: 96–100.

47. Range of presentations of GORD
Typical symptoms
(Heartburn/regurgitation)
Atypical symptoms
Complications
With oesophagitis
Chest pain (visceral hyperalgesia)
Oesophageal erosions and/or ulcers
Without oesophagitis
Hoarseness
(‘reflux laryngitis’)
Stricture
The primary symptom of GORD is heartburn with or without regurgitation.
However, there is a range of atypical symptoms, so it is important to consider GORD in patients presenting with these.
Although heartburn is in itself a relatively benign complaint and simple to manage in primary care, a range of complications are associated with GORD, some of which are very serious.
Background information on some of these symptoms is given in the next few slides.
Barrett’s oesophagus
Asthma, chronic cough, wheezing
Oesophageal adenocarcinoma
Dental erosions
Nathoo, Int J Clin Pract 2001; 55: 465–9.

48. Prevalence of heartburn or acid regurgitation%
Women: at least weekly episodes
Men: at least weekly episodes 40
Prevalence (%)
Heartburn due to acid reflux is common in men and women of all ages.
Data from a population-based study conducted in the USA indicate that the prevalence of heartburn is about 42%.
Acid regurgitation was reported by an additional 28% of patients.
These data are in line with prevalence rates of 34–44% heartburn reported in other studies.
The age- and sex-adjusted prevalence of frequent (at least once weekly) heartburn or acid regurgitation is about 20%.
These data are in line with age- and sex-adjusted prevalence rates of 15–21% frequent heartburn or acid regurgitation reported in other studies.
Most GPs will have many patients on their lists with GORD-related conditions.
It is important to treat this condition with respect – as the complications can be serious and are potentially fatal.
25–34 35–44 45–54 55–64 65–74
Age (years)
Locke et al., Gastroenterology 1997; 112: 1448–56.

49. GORD can be a trigger for asthma
100 80 77 72 65 60
Asthma patients experiencing GORD symptoms (%) 40
Asthma is an inflammatory disease with multiple triggers, one of which is GORD.
Data from three studies conducted among 448 adult asthma patients from France, Canada and the USA indicate that roughly 72% of asthma patients have GORD symptoms.
Modified from Harding & Sontag. Am J Gastroenterol 2000; 95 (Suppl): S23–32. 20
Perrin-Fayolle et al.
(n=150)
O’Connell et al.
(n=189)
Field et al.
(n=109)
Harding & Sontag, Am J Gastroenterol 2000; 95(Suppl): S23–32.

50. Correlation of respiratory and oesophageal symptoms with oesophageal acid events
Asthmatic patients with GORD (n=118)
Wheezing or
shortness of breath 65
Cough 98
Chest pain 60
Heartburn 83
Regurgitation 87
Nausea 91
Respiratory and oesophageal symptoms associated with oesophageal acid events (%)
Harding et al., Chest 1999; 115: 654–9.

51. Mechanism of asthma symptoms on exposure to oesophageal acid
Asthma symptoms plus oesophageal acid
Oesophageal acid-induced bronchoconstriction:
vagally mediated oesophageal bronchial reflex
heightened bronchial reactivity
microaspiration
Evidence of airway inflammation:
Substance P and tachykinin release
Increase:
minute ventilation
respiratory rate
Oesophageal acid has two major effects on respiratory symptoms:
bronchoconstriction
increasing minute ventilation and respiratory rate.
This results in a worsening of the symptoms of asthma.
Reproduced with permission.
Harding & Sontag, Am J Gastroenterol 2000; 95(Suppl): S23–32.

52. Chronic cough and GORD  Receptors  Cough centre VN Vagus nerve
N Cortical input
Using an anatomic diagnostic protocol, the cause of chronic cough can be determined in most cases, often leading to successful therapy.
GORD is one of the three most common causes of chronic cough – post-nasal drip syndrome and asthma are the other two most common causes.
When GORD is the cause of chronic cough, there may be no GI symptoms up to 75% of the time, leading to the term ‘silent GORD’.
24-hour oesophageal pH monitoring provides a sensitive and specific test for the presence of GORD and allows the evaluation of the temporal relationship between reflux and cough.
GORD-related cough may take 2–3 months to resolve with therapy.
A definitive diagnosis of cough resulting from GORD can only be made if the cough resolves with anti-GORD therapy.
Reproduced with permission.
Irwin & Madison, Am J Med 2000; 108(Suppl 4A): S126–30.

53. Effect of PPI on pulmonary and GI symptoms in asthma patients 14
Pulmonary symptoms score
Gastric symptom score 12 10
Symptom score 8 6 4 2
A double-blind, placebo-controlled, crossover study conducted with omeprazole 40 mg/day in 107 asthma patients with GORD.
Weekly pulmonary (cough, dyspnoea and wheezing) and gastric (regurgitation, heartburn and chest pain) symptoms scores fell during omeprazole therapy.
There was a significant improvement in the gastric symptom score with omeprazole compared to placebo (p=0.0001).
While pulmonary symptom scores also improved with omeprazole compared to placebo, this improvement was not significant (p=0.14). There was a small but statistically significant improvement in night-time asthma (p=0.04).
Note: Asthma is not an approved indication for omeprazole.
Reproduced with permission.
Weeks
Placebo
PPI
Kiljander et al., Chest 1999; 16: 1257–64.

54. Consequences of severe and prolonged GORD
Savary-Miller Grade IV and above
Oesophageal stricture
Barrett’s OE
OE Adenocarcinoma
Anemia
Oesophageal stricture
Barrett’s oesophagus
Oesophageal adenocarcinoma
Anaemia
Most patients present to the GP with heartburn or other symptoms of GORD.
Relatively few will present for the first time with the more serious symptoms of these conditions.
Management of these sequelae of GORD generally falls to the specialist.
Nathoo, Int J Clin Pract 2001; 55: 465–9.

55. Differential diagnosis of oesophageal stricture
Oesophageal cancer
Oesophageal spasm
GORD
Globus hystericus
Epiglottitis
Ingestion of caustic substances
Pharyngitis
Peritonsillar abscess
Foreign body
Oesophageal candidiasis
The differential diagnoses of oesophageal stricture are primarily conditions that restrict or block the oesophagus and impair swallowing.

56. Prevalence and risks of Barrett’s oesophagus in Europe/USA
Barrett’s found at endoscopy: 0.5–2%1
Barrett’s found while investigating GORD: 10–15%2,3
Barrett’s is common in white males4
Prevalence of adult heartburn: 20–40%3
Barrett’s increases the risk of oesophageal cancer 50–100-fold4
Barrett’s oesophagus is a condition in which the normal squamous epithelium of the oesophagus is replaced by metaplastic columnar epithelium.
This is a pre-malignant condition with a 50–100-fold (possibly even higher) increased risk of oesophageal cancer.
About 10–15% of patients with GORD will have Barrett’s oesophagus.
The condition is most common in white men.
20–40% of the adult population experience heartburn, the primary symptom of GORD. Barrett’s oesophagitis, along with stricture, is one of the complications of GORD.
Due to the increased risk of developing oesophageal adenocarcinoma, many gastroenterologists recommend regular (yearly or biennial) endoscopic screening with multiple biopsies to detect dysplasia in patients with Barrett’s oesophagus.
1. Jankowski et al., The Lancet 2000; 356: 2079–85.
2. Gore et al., Aliment Pharmacol Ther 1993; 7: 623–8.
3. Spechler. Digestion 1992; 51(Suppl 1): 24–9.
4. Peters et al., Gut 1999; 45: 489–94.

57. Mortality due to oesophageal adenocarcinoma in England and Wales
4000
3500
3000
Mortality
2500
2000
1500
1000
The number of patients developing adenocarcinoma of the oesophagus is increasing year on year.
500 79 84 89 94 97
Year
Office of National Statistics, 1999.

58. Heartburn as a risk factor for oesophageal adenocarcinoma
Frequency and duration of symptoms 20
Frequency
Chronicity
16.7
16.4
Odds ratio
7.5
6.3
5.1
5.2
Evidence shows that patients with a high frequency of episodes of heartburn or a long duration of heartburn symptoms are at increased risk of developing oesophageal adenocarcinoma.
Heartburn is one of the primary symptoms of GORD, so effective long-term management of GORD is likely to reduce the risk of the development of oesophageal cancer. 1 1
None 1 2–3 >3 0 <12 12–20 >20
Heartburn episodes/week Duration of symptoms (years)
Lagergren et al., N Engl J Med 1999; 340: 825–31.

59. Management of upper GI symptoms in primary care
Clinical history
Heartburn (GORD)
Upper abdominal pain/dyspepsia
Alarm features
Age >45
This algorithm summarizes the recommended management strategies for patients presenting to primary care physicians with upper GI symptoms.
Initial management of heartburn is in general practice – usually with a therapeutic trial of an antisecretory agent, such as a histamine-2-receptor antagonist (H2RA) or a proton pump inhibitor (PPI).
Early endoscopy is indicated if alarm features or atypical symptoms are present.
Alarm features include anaemia, weight loss, anorexia, recent onset of progressive symptoms (<3 months) melaena or haematemesis and dysphagia.
Manage with antisecretory agents
Early endoscopy
Test-and-treat for H. pylori
Treat empirically
Appropriate treatment

60. Alarm features for GORD
Odynophagia
Dysphagia
Bleeding
Alarm features
Alarm features for GORD include:
Dysphagia – difficulty swallowing
Odynophagia – pain on swallowing
Bleeding, which may present as melaena or haematemesis or result in anaemia.
Weight loss can also include anorexia.
The presence of one or more of these symptoms might indicate:
underlying cardiac disease that is presenting as heartburn
blockage of the oesophagus, possibly due to stricture or adenocarcinoma of the oesophagus.
Vomiting
Weight loss
Nathoo, Int J Clin Pract 2001; 55: 465–9.

61. European practice guidelines: GORD
Careful analysis of symptoms and history is key to diagnosis
Diagnosis based on symptoms can be aided by a trial of treatment
Clear endoscopic abnormalities are found in <50% of patients
Treatment should start with a proton pump inhibitor (PPI)
Most patients will require long-term treatment; anti-reflux surgery may be as effective as PPIs, but is less predictable
European practice guidelines are reflected in the conclusions of an international multidisciplinary workshop held in Genval, Belgium 1999.
This workshop took European and USA/Canadian guidelines into account, plus information from literature reviews and experience.
Like the USA guidelines, these guidelines also recommend the use of PPIs as first-line therapy.
PPIs are considered to be more effective than H2RAs for GORD therapy.
Summary of conclusions from a multidisciplinary workshop held in Genval, Belgium in 1999.
Dent et al., BMJ 2001; 322: 344–7.

62. When should endoscopy be considered in patients with GORD?
Alarm symptoms (e.g. dysphagia, weight loss, bleeding, abdominal mass)
Diagnostic problems (e.g. atypical symptoms)
Heartburn for 5 years or longer
Failure to respond to initial treatment
Pre-operative assessment
Early endoscopy should be considered in the situations outlined above.
Fewer than half of patients with GORD will have diagnostic endoscopic abnormalities, so endoscopy has a limited role in diagnosis.
Dent et al., BMJ 2001; 322: 344–7.

63. Differential diagnosis of GORD
Hiatus hernia
Oesophageal stricture
Oesophageal cancer
Chest pain of cardiac origin
Functional dyspepsia
Patients presenting with symptoms of GORD may have a range of underlying conditions, so it is important to take a careful history, including the duration, location and severity of symptoms.
If a simple trial of acid suppression is not successful in treating the symptoms, endoscopy will probably be required to establish a firm diagnosis.
Nathoo, Int J Clin Pract 2001; 55: 465–9.

64. Treatment options in GORD
Simple (lifestyle) measures
Medical treatment
antacids
acid secretion suppressors -
PPI, H2RAs, H.p. erad.
prokinetics
Surgery (laparascopic)

65. Lifestyle modifications for the management of GORD
Reduce weight
Elevate head
of bed
Stop smoking
Modifications
Avoid reflux-promoting agents (e.g. alcohol, coffee, some foods) (not evidence based)
Consider alternatives to reflux-promoting drugs (e.g. theophylline, anticholinergics)
As in all fields of medicine, lifestyle modifications are effective in the short term, but in the long term they require the patient to be highly motivated.
Changing diet, stopping smoking and losing weight are all difficult for patients to achieve long term.
Often patients will require counselling support and the use of antisecretory agents to remove symptoms while the lifestyle changes take effect.
Eat small meals,
no late meals, reduce fat

66. Antacids Antacids Increase the pH of gastric refluxate
Reduce the erosive effect and hence reduce symptoms
Suitable for quick relief of mild symptoms
Most antacids are not suitable therapies for established GORD or oesophagitis
Less effective than H2RAs or PPIs for treatment of GORD
Adverse effects include:
Accumulation in patients with renal impairment
Milk-alkali syndrome with high doses
Constipation
Diarrhoea
Antacids are effective for short-term relief of GORD symptoms, although their effectiveness has not been confirmed in controlled trials.
Many patients, particularly those who have not consulted their GP, rely on self-medication with antacids to control their symptoms.
Sonnenberg A, Pharmacoeconomics 2000; 17: 391–401.
de Caestecker, BMJ 2001; 323: 736–9.
Hatlebakk & Berstad, Clin Pharmacokinet 1996; 31: 386–406.
Scott & Gelhot, Am Fam Physic 1999; 59: 1161–9.

67. Mosapride: a novel prokinetic motility agent
1st selective 5-HT4 agonist
Available in Japan since 1998
Enhances gastrointestinal motility and emptying
Improved effect on gastric emptying vs cisapride
Better tolerated than cisapride
No cardiotoxicity issues (unlike cisapride)
Cisapride was available for many years, but has not achieved widespread first-line use in GORD.
Mosapride, which is better tolerated than cisapride may provide a good alternative.
Mine et al., Pharmacol Exper Ther 1997; 283: 1000–8.
Ruth et al., Aliment Pharmacol Ther 1998; 12: 35–40.

68. H2-receptor antagonists (H2RAs) H2-receptor antagonists (H2RAs)
Inhibit histamine stimulation of gastric parietal cell, resulting in reduced gastric acid secretion
Slower onset but longer duration of action than antacids
Cimetidine is associated with more drug interactions than other H2RAs, such as ranitidine
H2RAs are generally not as effective as PPIs for symptom relief or healing
Before the development of the PPIs, the H2RAs were the mainstay of antisecretory therapy.
Ranitidine is still extensively used by GPs in many countries, and remains on formularies and in local and national guidelines. However, there is good evidence that H2RAs provide poorer acid suppression than PPIs, and thus are less desirable for short- or long-term treatment.
de Caestecker, BMJ 2001; 323: 736–9.
Sonnenberg, Pharmacoeconomics 2000; 17: 391–401.

69. Available PPIs in Europe in 2002 Available PPIs in Europe in 2002
Omeprazole
Lansoprazole
Pantoprazole
Rabeprazole
Esomeprazole
But are they all the same?
These are the main PPIs currently available in Europe.

70. PPI bioavailability after the first dose90 80 70 60 50 40 30 20 10 80 77 64 52
Bioavailability (%) 40
Bioavailability following the first dose varies depending on the PPI.
Lansoprazole Pantoprazole Esomeprazole Rabeprazole Omeprazole
Tolman et al, J Clin Gastroenterol 1997; 24: 65–70.
Fitton & Wiseman, Drugs 1996; 51: 460–82.
Hassan-Alin et al, Gastroenterology 2000; 118: A16.
Swan et al., Aliment Pharmacol Ther 1999; 13(Suppl 3): 11–7.
Howden, Clin Pharmacokinet 1991; 20: 38–49.

71. Lansoprazole metabolism is unaltered with repeated dosing
CYP3A4
CYP2C19
Liver enzymes unaffected
Lansoprazole does not affect the liver enzymes that clear it from the blood.
Clinically, this means that there may be a reduced likelihood for drug interactions in patients taking lansoprazole.
Lansoprazole sulphone
Hydroxy lansoprazole
LAN
Tolman et al., J Clin Gastroenterol 1997; 24: 65–70.
Welage & Berardi, J Am Pharm Assoc 2000; 40: 52–62.

72. Healing rates for various PPIs in GORD Patients healed at 8 weeks (%)
L = lansoprazole P = pantoprazole O = omeprazole R = rabeprazole
30 = 30 mg/day, 20 = 20 mg/day, 40 = 40 mg/day
Petite et al. L30/O20
Castell et al. L30/O20
Mee et al. L30/O20
Mulder et al. L30/O40
Mossneret al. P40/O20
Corinaldesi et al. P40/O20
Hotz et al. P40/O20
Data from double-blind, randomised, multicentre controlled trials comparing GORD healing rates for PPIs.
Healing rates are generally comparable for lansoprazole and omeprazole, although there may be a trend for faster symptom relief with lansoprazole.
No difference in healing rates or symptom relief with pantoprazole and omeprazole, and rabeprazole and omeprazole.
Vicari et al. P40/O20
Thjodleifsson et al. R20/O20
Dekkers et al. R20/O20
Patients healed at 8 weeks (%)
Thomson, Curr Gastroenterol Rep 2000; 2: 482–93.

73. Nissen’s fundoplication for GORD

74. Clinical management of Barrett’s oesophagus
Acid suppression therapy with PPIs1
Surveillance endoscopy with biopsies
Mucosal ablation (electrocautery, laser or photodynamic therapy) combined with high-dose acid suppression
Oesophageal resection
Barrett’s oesophagus is one of the complications of GORD.
It can be managed in a number of ways, as listed here. Some of these management options are discussed in more detail in the following slides.
Note: PPIs are not indicated for Barrett’s oesophagus in all countries.
1. de Caestecker, BMJ 2001; 323: 736–9.

75. Conclusions Reflux symptoms are frequent throughout life
Incidence of oesophageal adenocarcinoma is rising:
Associated with increasing incidence of reflux and decreasing incidence of H. pylori
Heartburn is a risk factor for oesophageal adenocarcinoma:
Frequency
Duration
Severity
In summary:
GORD is common in adults of all ages.
The incidence of oesophageal adenocarcinoma – a complication of GORD – is rising.
Heartburn – the primary symptom of GORD – is a risk factor for oesophageal adenocarcinoma.
Oesophageal adenocarcinoma is associated with increased frequency, duration and severity of heartburn.
Hennessy, Postgrad Med J 1996; 72: 458–63.
Malfertheiner & Gerards, Baillière’s Clin Gastroenterol 2000; 14: 731–41.

76. Key points
Long-term GORD can result in serious complications, which may prove fatal
Early treatment of GORD is associated with excellent outcomes
Late treatment is associated with an increased risk of complications and potentially poor outcomes
Early intervention relieves symptoms and helps prevent serious complications
Early diagnosis and treatment is effective and prevents the serious, potentially fatal complications of GORD.

77. Mallory-Weiss syndrome
Bleeding from rupture of esophageal mucosa

78. Pill induced esophageal mucosal lesion

79. Portal hypertension – Esophageal varices

80. Esophageal varices