tbl 1 GERD, Barrett's Oesophagus, Achalasia and Oesophageal Cancers

Question 1

Gastro-Esophageal Reflux Disease – a condition when the reflux of stomach contents cause troublesome symptoms or complications (Montreal classification)
- Most common esophageal disorder – benign in nature
- Prevalence – more common in the West (10-20%) than in Asia (<5%)
o 0.5% in Singapore (Lim SL et al J Gastroenterol Hepatol 2005)
- Classic symptoms – heartburn (42%) and regurgitation (45%)
o Heartburn – burning sensation arising from the stomach or lower chest and radiating up to ___________
o Regurgitation – effortless return of food, acid, bilious material from the stomach into the mouth
o Together, these symptoms have a sensitivity 78%, specificity 60% for GERD
o Most commonly in the ______period (after meal)
o May be worse in supine position and when patient has just woken

Answer 1

retrosternal area/neck; postprandial

Question 2

Atypical clinical manifestations of GERD
- Alarm symptoms –
o Dysphagia – common in longstanding heartburn, often attributable to _________ but indicate esophageal stricture
o Odynophagia – unusual symptom of GERD but usually indicates an esophageal ulcer
o Weight loss and anaemia
§ Anaemia may be due to bleeding, reduced food intake and taking _____

Answer 2

reflux esophagitis; PPIs

Question 3

Clinical risk factors associated with GERD

Hiatus Hernia:

• Disruption of diaphragmatic sphincter, increasing susceptibility to reflux with raised __________
• Decreased threshold to induce transient lower esophageal sphincter relaxation (TLESR)
• Impairs esophageal acid clearance, ineffective esophageal motility and rereflux

Obesity

• Mechanism contributing to reflux incompletely understood
• Correlation of BMI/waist circumference with intragastric pressure and gastricoesophageal pressure gradient
• Associated with disruption of GEJ, leading to hiatus hernia and increased esophageal acid exposure Increased frequency of TLESR

Pregnancy

• Heartburn occurs in 30 to 50% of pregnancy
• Oestrogen and progesterone reduces LES tone and gravid uterus increasing intra-abdominal pressure

Diet and medication

• May induce LES hypotension
• Specific foods (fat, chocolate, peppermint), caffeine, alcohol, smoking
• Drugs e.g. anticholinergics, nitrates, Ca2+ blockers, TCA, opioids, ______

Answer 3

intra-abdominal pressure; diazepam

Question 4

Diagnosing GERD - based on classical symptoms alone
• Based on symptoms alone
– Classic clinical symptoms of heartburn, regurgitation
– Questionnaires eg _______

• Trial of proton pump inhibitors (PPI)
– 8 weeks in pts with classic reflux without alarm symptoms
• 78% sensitivity for GERD, specificity 54% (Numans et al. Ann Intern Med 2004)
– 3-4 months PPI trial for _________________-
– Not recommended for extra-esophageal syndrome without concomitant heartburn/regurgitation
– Resolution of symptoms is consistent with GERD
– Negative trial does not exclude GERD

• Look for __________
– Present: confirms GERD
– Severity of oesophagitis: LA classification
– Absent: does not exclude GERD

• Exclude complications of gerd
– Oesophageal ulcers, strictures, Barrett’s
oesophagus, adenocarcinoma

• Exclude other etiologies
– Infectious/pill/eosinophilic oesophagitis
– Oesophageal rings/webs/cancer

Answer 4

GERD-Q; extra-esophageal syndrome with concomitant heartburn/regurgitation; oesophagitis

Question 5

Tests for GERD 
• Indication for OGD: alarm symptoms
– Dysphagia, odynophagia, vomiting
– Loss of appetite, unintentional weight loss
– GI bleeding, iron deficiency anemia
– Not responding to PPI

• ______________
– Confirms diagnosis of GERD in patients with persistent symptoms (classic or atypical) despite PPI, no oesophagitis at endoscopy
– Determines presence of abnormal oesophageal acid exposure, reflux frequency and symptom association with reflux episodes

• Transnasal catheter
– Measures pH or impedence-pH over 24hrs
– Impedence-pH allows additional detection of ____________ (preferred modality)

• Wireless Capsule
– Extends pH monitoring to 48hrs and even up to 96hrs
– Increase yield of study

Answer 5

Ambulatory oesophageal pH monitoring; weakly acidic/non-acidic reflux

Question 6

Lifestyle modifications for GERD
• Strategies to reduce oesophageal acid exposure:
– weight loss (esp those with BMI>25, recent weight gain)
– raising head of bed
– avoid eating meals (esp with high ____ content) within 2-3 hrs of reclining

• Avoidance of food that precipitates reflux, worsens heartburn
– eg. coffee, alcohol, chocolate, fatty food
– eg. carbonated drinks, citrus food, spicy food
– Weak supporting evidence
– Selective elimination could be considered if patients noted correlation with reflux symptoms and improvement with elimination

Answer 6

fat

Question 7

Pharmacotherapy for GERD (part 1/2)

• Antacids
– Contains _________, aluminium hydroxide or calcium carbonate
– Neutralises gastric pH
– Effective in relieving heartburn symptoms within 5mins, short duration of effect 30- 60mins
– Do not prevent GERD nor heal oesophagitis

• Sodium alginate
– Forms viscous gum that floats within stomach and neutralises postprandial acid pocket in ________
– Relieves GERD symptoms in those with mild disease
– Often used in combination with antacids, eg. Gaviscon

• Histamine-2-receptor antagonist (H2RA)
– Eg Famotidine, ranitidine
– Inhibits H2 receptor on gastric parietal cell → decrease acid secretion
– Slower onset of action compared to antacids
– More effective than antacids at decreasing frequency and severity of heartburn
symptoms
– less effective at healing severe oesophagitis (grade 3-4 30-50%) compared to mild oesophagitis (grade 1-2 60-90%)
– Develops ______ within 2-6 wks, limits long term use

Answer 7

magnesium trisilicate; proximal stomach; tachyphylaxis

Question 8

Pharmacotherapy for GERD (part 2/2)

• Proton Pump Inhibitors (PPI)
– Eg. Omeprazole, esomeprazole, rabeprazole, pantoprazole, lansoprazole
– Inhibits H-K ATPase pump on _________→ decrease acid secretion
– Works best 30 mins before first meal of day
– More effective than H2RA: faster/more effective symptom relief, heals erosive oesophagitis
– No major difference in efficacy between various types of PPI
– Well tolerated – headaches, diarrhoea most common side effects
– Potential risks of hypochlorhydria
• Calcium malabsorption : OR 1.44 for hip fractures in pts > 1 yr on PPI ( age >50 )
• _______Deficiency : some pts show decreased levels after years of use
• Independent risk for ______ in antibiotic users
• Increased risk of community acquired pneumonia OR 1.73
• Acute interstitial nephritis (14%)
• Hypomagnesaemia (prolonged use >5 yrs, rare)

• Potassium-Competitive Acid Blocker (P-CAB)
– Eg Vonoprazan
– new generation of acid pump inhibitors
– Reversibly competes with the K+ channel of the H+K+ ATPase located in the apical membrane of parietal cells.
– Rapid rise in peak plasma concentration after oral dose
– Produce rapid acid inhibition and elevate intragastric pH generally to a higher level than PPIs
– T1/2 is 7-8hrs
– ADRs similar to long term high dose PPIs

Answer 8

gastric parietal cel; VitB12; C.Difficile diarrhoea

Question 9

Surgery for GERD
Surgery
• Indications:
– Failed optimal medical therapy
– Non-compliance, unwilling to take long term medication
– Presence of large hiatus hernia
– Oesophagitis refractory to medical therapy

• Type of surgery:
– Most common: _________________

• Recurrence of GERD post surgery can still occur
– Swedish study: 17.7% at median of 5.6yrs

Answer 9

laparoscopic Nissen Fundoplication

Question 10

Barrett’s Oesophagus
• Does not cause symptoms
• In 6-12% of pts undergoing OGD for symptomatic GERD
• In 1-2% of unselected pts going for OGD
• Predominantly a disease of ____________________
• Risk of adenocarcinoma 0.5% annually
– Long segment Barrett’s ( >3cm ) 30-125x risk compared to general population
– Short segment Barrett’s ( <3cm ) lower risk
• Rarely regresses even with _________

Answer 10

middle aged white males; high dose PPI

Question 11

Barrett’s Oesophagus Surveillance and Treatment

Surveillance via repeat ___________
– No dysplasia
• ________ surveillance

– Low grade dysplasia
• Endoscopic therapy
• _________ till no dysplasia is an acceptable alternative

– High grade dysplasia ( 30% risk of adenocarcinoma )
• Endoscopic therapy
• Endoscopic therapy
• Mucosal irregularity – Endoscopic mucosal resection
• Local ablative Tx – photodynamic therapy (PDT), radio-frequency ablation (RFA), Argon Plasma Coagulation (APC)
• Surgery – adenocarcinoma

Answer 11

gastroscopy (OGD); 3-5 yrly; 6-12mthly

Question 12

Achalasia
• Loss of peristalsis in the _______ + failure of lower oesophageal sphincter (LES) relaxation with swallowing
• Usually diagnosed between 25 and 60 years. Men = women.

• Clinical features:
– Insidious onset, gradual progressively worsening dysphagia for solids (91%) and liquids (85 %) and regurgitation of bland undigested food /saliva
– Retrosternal fullness after meal → induce vomiting
– Other symptoms: substernal chest pain, heartburn, and difficulty belching

• Suspect achalasia when:
– Dysphagia to both solids and liquids
– Refractory heartburn to trial of PPI
– Retained food in the oesophagus at upper endoscopy
– Increased resistance to passage of endoscope through the ____________

Answer 12

distal oesophagus; oesophagogastric junction

Question 13

Diagnosis of Achalasia

Manometry is required to establish the diagnosis of achalasia.
• Aperistalsis in the distal two-thirds of the oesophagus AND
• incomplete LES relaxation on conventional manometry (seen as elevated integrated relaxation pressure on high-resolution manometry, HRM)
• HRM has superceded conventional manometry nowadays

Barium esophagram
• Not a sensitive test. Normal in 1/3 of achalasia pts.
• Helps support diagnosis in equivocal manometry findings
• Aperistalsis, oesophageal dilatation, narrow EGJ junction, delayed emptying of barium

Exclude pseudo-achalasia
• Due to _______________
• OGD, endoscopic ultrasound, CT scan

Answer 13

cancer at the EGJ junction

Question 14

Achalasia – natural history
• Progressive dilation of oesophagus without treatment – Late/end stage disease: _____________, severe dilation/megaoesophagus (diameter >6cm)
– Some patients may require oesophagectomy
• Increased risk of oesophageal cancer
– Absolute risk remains low (annual incidence of 0.34% Leeuwenburgh I et al AJG 2010)
– Endoscopic surveillance not recommended

Answer 14

oesophageal tortuosity

Question 15

Achalasia - Treatment

• Aim: decrease resting pressure at lower oesophageal sphincter (LES)

• Mechanical disruption of muscle fibres of LES
– Pneumatic dilatation (PD)
– Laparoscopic Heller myotomy (LHM)
– Per-oral endoscopic myotomy (POEM) – increasing popularity with promising results in expert centres but not standard of care yet

• Pharmacologic reduction in LES pressure
– Botulinum toxin injection of the LES

• High risk for complications (eg elderly) for surgery, pneumatic dilation, POEM
– Medications
• Include nitrates, ___________
• Limited efficacy, temporizing, has side effects
• Can be considered if no other better options

Answer 15

calcium channel blockers

Question 16

Achalasia
●Type I (classic achalasia) – Swallowing results in no significant change in esophageal pressurization. By CC-3 criteria, type I achalasia has 100 percent failed peristalsis as indicated by a distal contractile integral (DCI, an index of the strength of distal esophageal contraction) <100 mmHg.

●Type II – Swallowing results in simultaneous pressurization that spans the entire length of the esophagus. According to CC-3, type II achalasia has 100 percent failed peristalsis and pan-esophageal pressurization seen in ≥20 percent of swallows.

●Type III (spastic achalasia) – Swallowing results in premature and often lumen-obliterating contractions or spasms. By CC-3 criteria, type III achalasia has no normal peristalsis and premature (spastic) contractions with distal latency <4.5 seconds and DCI >450 mmHg·s·cm seen in ≥20 percent of swallows.

Type I is the most frequent and best treatment response. For type III, it is the least common, worst treatment, least responsive to pneumatic dilation, most responsive to ___________

Answer 16

Heller myotomy

Question 17

Oesophageal cancer
• Squamous cell carcinoma (SCC) or oesophageal adenocarcinomas (EAC) accounts for >95% of oesophageal malignant tumors

• Incidence rates varies internationally:
– High risk area: From Northern Iran to North-Central China (oesophageal cancer belt) : 90% SCC
– Low risk area: United States, Western countries:

• SCC decreasing, EAC rising (from Barrett’s oesophagus), rising risk factors of overweight, obesity

• Risk factors:
– SCC risks: Blacks, Asians, alcohol, smoking, aerodigestive SCC, ________, _____, tylosis, dietary factors (lacking vegetables/fruits, hot beverages >65 °C(hot tea/coffee, chewing areca nuts/betel leaves). (OBESITY not linked to SCC)

– EAC risks: Whites, male gender, GERD, Barrett’s oesophagus, obesity, smoking,. (ALCOHOL not linked to EAC)

Answer 17

oesophageal caustic strictures; achalasia

Question 18

Oesophageal SCC and EAC

• Location:
– SCC occurs in _________
– EAC usually in distal esophagus, EGJ, gastric cardia region

• Both EAC and SCC have early lymphatic spread
– Lymphatics in the oesophagus located in the _______ in contrast to the rest of the GI tract, where they are located beneath the muscularis mucosa.

• Symptoms:
– early no symptoms, dysphagia (more solids), weight of loss, regurge of undigested food, voice hoarseness (__________ damage), aspiration, iron deficiency anaemia, rarely upper BGIT, cough with eating (trachea-esophageal fistula)

Answer 18

mid-portion esophagus; recurrent laryngeal nerve

Question 19

Oesophageal Cancer: Diagnosis
• Diagnosis: usually by ________ (>90% of cases)
• Early cancers may appear as _______, nodules, or ulcerations.
• Advanced lesions may appear as strictures, ulcerated masses, circumferential masses or large ulcerations.

Answer 19

endoscopic biopsy; superficial plaques

Question 20

Esophageal Cancer: Staging
• ___________scan to evaluate for the presence of metastatic disease (M)
• If no metastatic disease, consider __________ for more detailed tumour and nodal staging (T,N)
• Integrated PET/CT scans are useful to detect occult metastatic disease in patients who are otherwise believed to be surgical candidates after routine CT staging.
• Role of staging laparoscopy is controversial (no consensus on this)
• Preoperative bronchoscopy with biopsy and brush cytology for locally advanced non-metastatic tumours that are located at or above the level of the carina

Answer 20

Computed tomography (CT); endoscopic ultrasonography (EUS)

Question 21

Esophageal Cancer: Management
• Majority undergo some form of combined modality therapy rather than local therapy alone.
• However, the optimal management remains controversial.
• However, it remains unclear whether and how histology (SCC vs EAC) should be used to select the treatment approach.

• Thoracic oesophageal cancer
– Neoadjuvant chemo-RT followed by surgery rather than surgery alone, for patients with T3N0, T4aN0, and clinically node-positive thoracic esophageal cancer, regardless of histology
– Clinical stage T2N0 tumours is less clear but ___________- for patients showed survival benefit.
– T1N0 oesophageal or EGJ adenocarcinoma or SCC, ________ is recommended.
• Definitive chemo-RT is reasonable if not surgical candidate.

• EGJ (oesophagogastric junction) cancers
– Most clinicians now treat EGJ and proximal gastric(cardia) cancers as oesophageal cancers with preoperative chemo-RT.
– Institutional practice may vary due to different trials.

• Cervical oesophageal cancer
– This is more closely related to SCC of the head and neck than for malignancies involving the more distal portions of the esophagus.
– In general, chemo-RT is preferred over surgery alone for these patients since survival appears to be the same and major morbidity is avoided (no surgery).

Answer 21

preoperative chemo-RT; surgery alone