Gastroesophageal reflux disease (GERD) is caused by the backflow of gastric contents into the esophagus, resulting in heartburn and regurgitation that affects 30% of the population. Common complications of long-term and severe GERD include esophagitis, Barrett's esophagus which increases cancer risk, and benign esophageal strictures. Lifestyle modifications and medications like PPIs are first-line treatments for GERD symptoms and healing esophagitis, while surgery may be considered for refractory cases or complications.

1. Gastroesophageal Reflux Disease (GERD) Any symptoms or esophageal mucosal damage,causing discomfort, that results from reflux of gastric acid into the esophagus GERD resulting in heartburn affects 30% of the general population Classic GERD symptoms Heartburn (pyrosis): substernal burning discomfort Regurgitation: bitter, acidic fluid in the mouth when lying down or bending over

2. High Prevalence of Gastroesophageal Reflux Symptoms

4. Important Reasons to Diagnose and Treat GERD Negative impact on health-related quality of life 1 Risk factor for esophageal adenocarcinoma 2 Revicki et al. Am J Med 1998;104:252. Lagergren et al. N Engl J Med 1999;340:825.

5. Pathophysiology: Occasional episodes of GERD are common in health. Reflux is normally followed by oesophageal peristaltic waves which efficiently clear the eso, alkaline saliva neutralises residual acid& symptoms do not occur. GERD develops when the oesophageal mucosa is exposed to gastric contents for prolonged periods of time, resulting in symptoms & in a proportion of cases, oesophagitis. Several factors are known to be involved:

7. 1.AbnormaL LES: In health, LES is tonically contracted, relaxing only during swallowing. Some patients with GERD have reduced LES, permitting reflux when intra-abdominal pressure rises. In others, basal sphincter tone is normal but reflux occurs in response to frequent episodes of inappropriate sphincter relaxation

8. 2.HH: Hiatus hernia causes reflux because: A. The pressure gradient between the abdominal & thoracic cavities, which normally pinches the hiatus, is lost. B. The oblique angle between the cardia& oesophagus disappears. Many patients who have large hiatus hernias develop reflux symptoms, but the relationship between the presence of a HH& symptoms is poor. Hiatus hernia is very common in individuals who have no symptoms& some symptomatic patients have only a very small or no hernia. Nevertheless, almost all patients who develop oesophagitis, Barrett's oesophagus or peptic strictures have a hiatus hernia.

9. 2.HH: IMPORTANT FEATURES OF HIATUS HERNIA Herniation of the stomach through the diaphragm into the chest Occurs in 30% of the population > 50 years Often asymptomatic Heartburn & regurgitation can occur Gastric volvulus may complicate large para-oesophageal hernias

11. 3.Delayed oesophageal clearance : Defective oesophageal peristaltic activity is commonly found in patients who have oesophagitis. It is a primary abnormality, since it persists after oesophagitis has been healed by PPI. Poor oesophageal clearance leads to increased acid exposure time.

12. 4.Gastric contents Is the most important oesophageal irritant& there is a close relationship between acid exposure time & symptoms.

13. 5. Defective gastric emptying Gastric emptying is delayed in GERD. The reason for this is unknown.

14. 6. Others Recent attention on the importance of duodenogastro-oesophageal reflux, containing bile, pancreatic enzymes&pepsin in addition to acid.

15. 7. Increased inra abd pressure: Pregnancy Obesity: Weight loss may improve symptoms

16. 6. Diet / environmental factors : Dietary fat, chocolate, alcohol , coffee relax LES & provoke symptoms. There is little evidence to incriminate smoking or NSAIDs as a causes.

17. Clinical features The major symptoms are heartburn /regurgitation, often provoked by bending, straining or lying down. 'Waterbrash‘: salivation from reflex salivary gland stimulation as acid enters the eso, is often present. A history of weight gain is common. Some patients are woken at night by choking as refluxed fluid irritates the larynx. Others develop odynophagia or dysphagia. A few present with atypical chest pain which may be severe, can mimic angina probably due to reflux-induced oesophageal spasm.

18. Clinical features Classic GERD Extraesophageal/Atypical GERD Complicated GERD Clinical Presentations of GERD

20. Extraesophageal Manifestations of GERD Pulmonary Asthma Aspiration pneumonia Chronic bronchitis Pulmonary fibrosis Other Chest pain Dental erosion ENT Hoarseness Laryngitis Pharyngitis Chronic cough Globus sensation Dysphonia Sinusitis Subglottic stenosis Laryngeal cancer

21. Potential Oral & Laryngopharyngeal Signs Associated with GERD Edema /hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia & lymphoid hyperplasia of posterior pharynx Interarytenyoid changes Dental erosion Subglottic stenosis Laryngeal cancer Vaezi MF, Hicks DM, Abelson TI, Richter JE. Clin Gastro Hep 2003;1:333-344.

22. Pathophysiology of Extraesophageal GERD

23. Complications: 1. Oesophagitis A range of endoscopic findings, from mild redness to severe. With bleeding, ulceration &stricture formation. There is a poor correlation between symptoms, histological &endoscopic findings. Significant GERD may be present despite normal endoscopy / normal oesophageal histology.

24. Complications: Oesophagitis

25. Complications:2.Barrett's oesophagus ‘ Columnar lined oesophagus'-CLO, is a pre-malignant glandular intestinal metaplasia of the lower oeso, in which the normal squamous lining is replaced by columnar mucosa. Occurs as an adaptive response to chronic GERD,found in 10% undergoing gastroscopy for reflux symptoms. CLO is the major risk factor for oesophageal adenocarcinoma, with a lifetime cancer risk of 10%, more closely related to the severity& duration of reflux rather than the CLO per se. The cancer incidence is estimated at 1/200 patient years (0.5% /year), being low& > 95% with CLO die of causes other than oesophageal cancer. Prevalence is increasing, more in men (especially white) &> 50. It is weakly associated with smoking but not alcohol. E-cadherin polymorphisms, p53 mutations, TGF-β, EGF receptors, COX-2& TNF-α may play roles.

26. Barrett Diagnosis:diagnosis Requires multiple systematic biopsies to maximise the chance of detecting intestinal metaplasia /or dysplasia.

27. Barret:Management Neither PPI nor antireflux surgery will stop progression or induce regression of CLO& treatment is only indicated for symptoms of reflux or complications such as stricture. Endoscopic ablation therapy or photodynamic therapy can induce regression but 'buried islands' of glandular mucosa may persist underneath the squamous epithelium& cancer risk is not eliminated. At present these therapies remain experimental but show promise; they are also used in patients with high-grade dysplasia (HGD) or early malignancy who are not suitable for surgery.

28. Barret: Management Regular endoscopic surveillance can detect dysplasia& malignancy at an early stage & improve 2-year survival but, because most CLO is undetected until cancer develops, surveillance strategies are unlikely to influence the overall mortality rate of oesophageal cancer. Surveillance is expensive &cost-effectiveness conflicting. Surveillance is currently recommended every 2-3 years for those without dysplasia & at 6-12-monthly intervals for those with low-grade dysplasia. Oesophagectomy is widely recommended for those with HGD as the resected specimen harbours cancer in up to 40%. Recent data suggest that HGD often remains stable & may not progress to cancer, at least in the medium term. Close follow-up with biopsies every 3 months is an alternative strategy for those with HGD.

29. Complications:3. IDA Occurs as a consequence of chronic, insidious blood loss from long-standing oesophagitis. Almost all such patients have a large hiatus hernia& bleeding can occur from subtle erosions in the neck of the sac ('Cameron lesions

30. Complications: 4.Benign oesophageal stricture Develop as a consequence of long-standing oesophagitis. Most elderly & have poor oesophageal peristaltic activity. Present with dysphagia which is worse for solids than liquids. Bolus obstruction following ingestion of meat causes absolute dysphagia. A history of heartburn is common but not invariable;as in many elderly patients. Diagnosis is made by endoscopy, with biopsies to exclude Cancer. Endoscopic balloon dilatation or bouginage is helpful. Subsequently, long-term therapy with a PPI at full dose should be started to reduce the risk of recurrent oesophagitis & stricture formation.

31. GERD:Investigations Young patients with typical symptoms, without worrying features such as dysphagia, weight loss or anaemia, can be treated empirically without investigation. Investigation is advisable if patients present in middle or late age, if symptoms are atypical or if a complication is suspected. Endoscopy is the investigation of choice, performed to exclude other upper GI diseases & identify complications. A normal endoscopy in a patient with compatible symptoms should not preclude treatment for GERD. Twenty-four-hour pH monitoring is indicated if, despite endoscopy, the diagnosis is not clear. A pH of < 4 for > 6-7% of the study time is diagnostic of GERD.

33. When to Perform Diagnostic Tests Uncertain diagnosis Atypical symptoms Symptoms associated with complications Inadequate response to therapy Recurrent symptoms Prior to anti-reflux surgery

34. Diagnostic Tests for GERD Barium swallow Endoscopy Ambulatory pH monitoring Esophageal manometry

35. Barium Swallow Useful first diagnostic test for patients with dysphagia Stricture (location, length) Mass (location, length) Bird’s beak Hiatal hernia (size, type) Limitations Detailed mucosal exam for erosive esophagitis, Barrett’s esophagus

36. Endoscopy Indications for endoscopy Alarm symptoms Empiric therapy failure Preoperative evaluation Detection of Barrett’s esophagus Detect grade: LA grading classification system for GERD.

37. The LA Classification system – Grade A reflux esophagitis Stomach Grade A : One (or more) mucosal break, no longer than 5 mm, that does not extend between the tops of two mucosal folds.

38. The LA Classification system – Grade B reflux esophagitis Stomach Grade B : One (or more) mucosal break, more than 5 mm long, that does not extend between the tops of two mucosal folds.

39. The LA Classification system – Grade C reflux esophagitis Stomach Grade C : One (or more) mucosal break that is continuous between the tops of two or more mucosal folds, but which involves less than 75% of the circumference.

40. The LA Classification system – Grade D reflux esophagitis Stomach Grade D : One (or more) mucosal break that involves at least 75% of the esophageal circumference.

41. Ambulatory 24 hr. pH Monitoring Physiologic study Quantify reflux in proximal/distal esophagus % time pH < 4 DeMeester score Symptom correlation

42. Ambulatory 24 hr. pH Monitoring Normal GERD

43. Wireless, Catheter-Free Esophageal pH Monitoring Improved patient comfort / acceptance Continued normal work, activities&diet study Longer reporting periods possible (48 hours) Maintain constant probe position . Potential Advantages

44. Esophageal Manometry Assess LES pressure, location / relaxation Assist placement of 24 hr. pH catheter Assess peristalsis Prior to antireflux surgery Limited role in GERD

45. Treatment Goals for GERD Eliminate symptoms Heal esophagitis Manage or prevent complications Maintain remission

46. Management: Life-style Weight loss Avoidance of dietary items that worsen symptoms. Elevation of the bed head in those who experience nocturnal symptoms Avoidance of late meals Modify diet Eat more frequent but smaller meals Avoid fatty/fried food, peppermint, chocolate, alcohol, carbonated beverages, coffee and tea. Avoid eating within 2-3 hours of bedtime. Giving up smoking.

47. Management: antacids Proprietary antacids &alginates also provide symptomatic benefit. H2-receptor antagonist drugs also help symptoms without healing oesophagitis. PPI are the treatment of choice for severe symptoms &for complicated reflux disease PPI are better than H2Bs in healing oesophagitis& relieving symptoms. Symptoms almost invariably resolve& oesophagitis heals in the majority of patients. Recurrence of symptoms is common when therapy is stopped& some require life-long treatment at the lowest acceptable dose.

48. Effectiveness of Medical Therapies for GERD Treatment Response Lifestyle modifications/antacids 20 % H 2 -receptor antagonists 50 % Single-dose PPI 80 % Increased-dose PPI up to 100 %

49. Treatment Modifications for Persistent Symptoms Improve compliance Optimize pharmacokinetics Adjust timing of medication to 15 – 30 minutes before meals (as opposed to bedtime) Allows for high blood level to interact with parietal cell proton pump activated by the meal Consider switching to a different PPI as esmo or rebeprazol.

50. GERD is a Chronic Relapsing Condition Esophagitis relapses quickly after cessation of therapy > 50 % relapse within 2 months > 80 % relapse within 6 months Effective maintenance therapy is imperative

51. GERD IN OLD AGE Prevalence: higher. Severity of symptoms: does not correlate with the degree of mucosal inflammation. Complications: late complications as peptic strictures or bleeding from oesophagitis are more common. Recurrent pneumonia: consider aspiration from occult GERD.

53. Erosive Esophagitis

54. Peptic Stricture Barium Swallow Endoscopy

55. Esophageal Stricture: Dilating Devices

56. TTS Balloon Dilation of a Peptic Stricture

57. Barrett’s Esophagus

58. Esophageal Cancer Barium Swallow Endoscopy

60. When to Discuss Anti-Reflux Surgery with Patients Intractable GERD – rare Difficult to manage strictures Severe bleeding from esophagitis Non-healing ulcers GERD requiring long-term PPI-BID in a healthy young patient Persistent regurgitation/aspiration symptoms Not Barrett’s esophagus alone

61. Endoscopic GERD Therapy Endoscopic antireflux therapies Radiofrequency energy delivered to the LES Stretta procedure Suture ligation of the cardia Endoscopic plication Submucosal implantation of inert material in the region of the lower esophageal sphincter Enteryx

62. Time is cruel: