GORD

Definitions:

GORD: When reflux of stomach contents causes troublesome symptoms and/or complications
- Progressive disease if no intervention
- Real risk of primary and secondary complications
Refractory GORD: Defined as partial or lack of response to PPI BD

Anatomy:

Defective lower oesophageal sphincter has:
- Pressure <6mm Hg or
- Total length <2cm or
- Abdominal length <1cm

Risk factors

Factors increasing intra-abdominal pressure
- Obesity
  - Increased intra-abdominal pressure, decreased LOS pressure, impaired oesophageal body peristalsis, more frequent transient LOS relaxations
  - Can often be asymptomatic - 45% of patients getting worked up for bariatric surgery have silent reflux
- Pregnancy
  - Oestrogen and progesterone decrease LOS tone
  - Gravid uterus
Factors compromising GOJ
- Smoking
- Hiatus hernia
  - Severity correlates with size of hernia
  - Impaired crural diaphragmatic component of GOJ, low LOS pressure, reduced threshold for eliciting transient LOS relaxation in response to gastric distension
- Drugs
  - Anticholinergics
  - Nitrates
  - Calcium channel blockers
  - Tricyclic antidepressants
  - Opioids
  - Theophylline
  - Diazepam
  - Barbiturates
Factors increasing acidity of gastric secretions
- Lifestyle
  - Fat, chocolate, peppermint, caffeine, alcohol
- Zollinger-Ellison syndrome
Other
- Structural
- Mechanical
- Genetic
- H Pylori possibly protective - negative risk factor for reflux - thought to be due to atrophic gastritis

Physiology

Gastric acid production - parietal cells in fundus and body of stomach
- Neurological - vagus stimulates parietal cells through ACh
- Endocrine - gastrin activates parietal cells
- Paracrine - histamine from enterochromaffin-like cells
Normal mechanisms clearing acid from oesophagus:
- Peristalsis is usually effective in returning fluid to stomach
- Swallowed saliva contains bicarbonate, which can neutralise acid

Pathophysiology

GORD occurs when intra-gastric pressure is greater than high-pressure zone of the distal oesophagus
- Resting LOS pressure is too low (frequently associated with hiatal hernia - displacement of GOJ into the posterior mediastinum)
- Inappropriate relaxation of LOS in the absence of peristaltic contraction of the oesophagus (can occur in normal anatomic position)
Some degree of GORD is physiological, occurring in the setting of a normal LOS. Allows us to rapidly evacuate swallowed air from the stomach, that would otherwise cause bloating and flatulence.
- Pathological GORD occurs with greater oesophageal acid exposure, worse symptoms, and the presence of mucosal damage of the oesophagus
Hiatal hernias often associated with GORD - abnormal anatomy compromises the LOS
- See separate topic

Symptoms - oesophageal, extra-oesophageal and complications

Typical symptoms: heartburn, regurgitation, water brash
- Volume reflux which is worse lying down and responds to PPIs
- Heartburn - epigastric or retrosternal caustic or stinging sensation, which does not typically radiate to the back, and is not described as a pressure sensation
- Water brash - sour taste described as either acid or bile
- Regurgitation - generally of digested food. Regurgitation of undigested food suggests oesophageal diverticulum or achalasia.
Differentiate between pathological and physiological:
- Physiological - short-lived, asymptomatic, post-prandial, not during sleep
- Pathological - often occurs nocturnally. A/w symptoms or mucosal injury
Atypical symptoms: consider GORD in dysphagia, chest pain, globus, odynophagia, cough/hoarseness/wheeze, sometimes nausea
- Dysphagia occurs with reflux-associated inflammatory processes of the oesophageal wall (Schatzki ring, diffuse distal oesophageal inflammation, peptic stricture - pathognomic for long-standing reflux). Can functionally shorten the oesophagus, making operations harder.
Extra-oesophageal symptoms:
- Laryngeal - hoarseness/dysphonia, throat clearing, throat pain, globus, choking, post-nasal drip, laryngeal and tracheal stenosis, laryngospasm, contact ulcers.
- Pulmonary - cough, shortness of breath, wheezing, pulmonary disease (asthma)
  - Patients with asthma and GORD can see an improvement rate of 90% of children and 70% of adults in their asthma symptoms after anti-reflux surgery
  - Idiopathic pulmonary fibrosis is possibly caused by GORD in some cases (as many as 94% of patients with IPF have been shown to have GORD)
- Occur due to
  - Proximal oesophageal reflux and micro-aspiration of gastroduodenal contents causing direct caustic injury to the larynx and lower respiratory tract
  - Distal oesophageal acid exposure triggering a vagal cough/bronchospasm reflux, due to common vagal innervation of trachea and oesophagus
- Variable response to PPI, even if these symptoms are due to GORD
- Need to thoroughly evaluate these patients for other causes (?ENT/resp referral). If no other cause found, Sabiston says anti-reflux surgery has a 70% success rate.
Alarm symptoms (complications): dysphagia, early satiety, haematemesis, melaena, vomiting, weight loss

Examination

Not really helpful
Supraclavicular lymphadenopathy
Yellow/poor dentition

Differentials:

Dysphagia: Oesophageal rings/webs, oesophageal motility disorder
Slowly progressive dysphagia: Strictures/cancers
Odynophagia: infectious or medication-induced oesophagitis
PUD
Coronary artery disease
Cholelithiasis

Workup:

Barium swallow
- Not diagnostic, although mucosal changes may be seen. Useful for excluding differentials (diverticula, tumours, strictures, achalasia, dysmotility, gastroparesis)
- Allows definition of hiatal hernia
Gastroscopy
- Indications for gastroscopy:
  - Alarm features present and no endoscopy within three months
    - New onset of dyspepsia in patient >60 years
    - Evidence of GI bleeding
    - Iron deficiency anaemia
    - Anorexia
    - Unexpained weight loss
    - Dysphagia
    - Odynophagia
    - Persistent vomiting
    - Gastrointestinal cancer in first-degree relative
  - Screen for Barrett's oesophagus if they have multiple risk factors and also have had GORD for 5-10 years:
    - Age >50
    - Male
    - White
    - Hiatal hernia
    - Obesity
    - Nocturnal reflux
    - Smoker
    - First-degree relative with Barrett's and/or adenocarcinoma
- Findings:
  - 70-85% of patients with symptoms defined as GORD have no evidence of oesophagitis on endoscopy
  - Should be classified on upper endoscopy to
    - Erosive oesophagitis - visible breaks in distal oesophageal mucosa
    - Nonerosive reflux disease - no visible breaks
  - Ulcerations in distal oesophagus
  - Look for peptic strictures, Barrett's metaplasia, oesophageal adenocarcinoma
  - Assess GOJ - retroflex 180 degrees in the stomach to visualise from below, and grade according to Hill classification (see 'gastroscopy technique')
  - Note any hiatus hernia
  - Grade severity of erosive oesophagitis. Most common scheme is Los Angeles classification (LA)

A
B
C
D

Peptic strictures and LA class C and D oesophagitis can be considered pathognomic for GORD, rendering pH monitoring unnecessary

Oesophageal manometry
- Assesses function of oesophageal body and LOS
- Indications:
  - Can be used in patients that might have a motility disorder - chest pain, dysphagia, normal upper endoscopy.
  - Also should be done prior to anti-reflux surgery
  - Main reason is to exclude motility disorders which might be made worse by an operation
Ambulatory pH monitoring - gold standard
- Indications:
  - Refractory GORD/typical symptoms but no improvement with PPI
  - Useful to correlate symptoms with reflux and quantify oesophageal acid exposure
  - Doubt over cause of oesophagitis - as in LA class A and B oesophagitis
- Technique:
  - Need to stop PPI/antisecretory/antacids 2 weeks before
  - One way is via trans-nasal probe, alternatively implant a Bravo capsule just above GOJ which communicates with a bluetooth device
  - Patient also tracks their symptoms for correlation
  - Calculate DeMeester score: >14.72 confirms pathologic GORD
    - Uses factors for the score such as total number of reflux episodes, length of episodes, number of episodes lasting >5 minutes, percentage of time spent in reflux in upright and supine positions
- Peptic strictures can cause false-negative pH studies - ideally done after dilatation of the stricture and biopsied
Oesophageal impedance monitoring
- Identifies episodes of non-acid reflux
- Often done in conjunction with pH monitoring
Gastric emptying study
CT
Colonoscopy

Approach:

New patients with GORD:

- Consider gastroscopy if:
  - Alarm features
  - Risk factors for Barrett's and no endoscopy past 5-10 years
  - Atypical symptoms
- Consider investigation to exclude alternative diagnoses
- Trial 8 weeks PPI
  - Improvement - no further investigation
  - No improvement - more extensive investigation
  - Still no improvement or diagnosis - treat as refractory GORD

Refractory GORD:

- Review PPI compliance - serum gastrin level should generally be 200-400pg/mL and only rarely above 500
- Gastroscopy if not already done
- Consider manometry and ambulatory pH monitoring
- Review associated factors below
- Manage medically as per UTD algorithm
- Consider whether they are likely to have a good response from surgery

Management:

Lifestyle (not proven very much)

- Weight loss (if overweight)
- Elevation of bed head
- Eliminate fatty foods, caffeine, chocolate, spicy foods, etc
- Don't eat right before bed
- Smaller, more frequent meals
- Quit smoking and drinking
- Elimination of constipation

Medical

- PPI
  - Irreversibly binds the H+, K+-ATPase proton pump in parietal cells
  - Require an acidic environment to be activated - may not work properly with sucralfate/antacids
  - Maximal pharmacologic effect occurs about 4 days after initiation, and effect lasts for the life of the parietal cell (1 week)
  - Maximal: BD PPI
  - Side effects
    - Short-term: headache, abdo pain, flatulence, constipation, diarrhoea
    - Reports of long-term associations with dementia and bone density issues are based on observational studies and are hard to prove. 2024 expert opinion is that these risks should be de-emphasised. The true long-term risks are probably slightly higher risk of gut infection and electrolyte irregularities, including hypomagnesaemia.
- H2-receptor antagonists
  - Inhibit the histamine receptor on the parietal cell
  - Famotidine is the most potent, followed by ranitidine, nizatidine, and cimetidine
- Antacids
  - Contain aluminium hydroxide, calcium carbonate, or magnesium trisilicate
  - Magnesium antacids - best buffers, but can cause diarrhoea
  - Phosphorus antacids - occasionally result in hypophosphataemia and constipation
  - Neutralise gastric acid and decrease acid delivery to the duodenum, although the precise mechanism is unclear
- Sucralfate
  - Sucrose octasulfate complexed with aluminium hydroxide
  - Binds to injured gastric tissue and simulates angiogenesis and granulation tissue formation
  - Lasts for about 6 hours

Surgery

- Indications:
  - Typical symptoms + objective signs (significant oesophagitis, Barrett's, hiatus hernia) = offer operation if medical management fails, generally with a screening Barium swallow beforehand to exclude dysmotility (manometry if concerning features for dysmotility)
  - Atypical symptoms and/or lack of objective signs: refer for oesophageal manometry and pH, and operate based on DeMeester score
  - Haematemesis
  - Iron deficiency anaemia due to Cameron lesions
  - Chest pain due to recurrent volvulus
- Predictors of good response:
  - Best results in those with abnormal 24-hr pH score, typical primary symptoms and response to PPI (=90% will have good or excellent result)
    - Typical symptoms = heartburn, acid regurgitation
    - Atypical is cough, globus, hoarse voice, odynophagia, sore throat, etc = less predictive of good result from surgery
    - Be very wary of patients with atypical symptoms or a history of not responding to PPI - should confirm pathological acid reflux with at least two objective tests prior to offering surgery
  - Best chance of positive outcome in those <50yo
  - Recurrent reflux more common in women, obese
- Hiatus hernia and GORD
  - Plan intervention based on the degree that each problem is thought to be contributing to symptoms
  - Hiatus hernia is likely to be the dominant process when main symptoms are dysphagia, food sticking, early satiety, regurgitation, chest pain and vomiting
    - Will likely have relief with abdominal gastropexy and partial wrap
- Obesity and GORD
  - RYGB can be a good way of simultaneously controlling GORD and obesity - excludes most parietal cells from contact with oesophagus, and also prevents duodenal acid from contacting oesophagus
  - Consider RYGB instead of fundoplication
  - Fundoplication should rarely be considered in patients with BMI > 40
  - Avoid doing a sleeve gastrectomy in patients with GORD
  - GORD with previous RYGB
    - Cause - overly large gastric pouch, gastrogastric fistula, hiatal hernia
    - Hard to do fundoplication due to lack of fundus
    - Options - close gastrogastric fistula, correct hiatal hernia, revise large gastric pouch, magnetic sphincter implantation
  - GORD with previous sleeve gastrectomy
    - Hard to do fundoplication due to lack of fundus
    - Options - convert to RYGB or fix the hiatus hernia or magnetic sphincter implantation
- Ineffective oesophageal motility
  - Toupet/Dor might be safer than Nissen, to prevent dysphagia
  - However, remains controversial, and total fundoplication will probably give better control in the long run
  - If there is a total absence of oesophageal body contractility, much stronger indication for partial fundoplication only
- Barrett's oesophagus
  - About half of patients with BE see endoscopic regression after anti-reflux surgery
  - Should not be considered an indication for anti-reflux surgery alone
  - If you do operate, need to continue endoscopic surveillance
- Young healthy patient with small HH and GORD
  - Manage with PPI and lifestyle until requiring BD PPI and getting breakthrough symptoms

Refractory GORD:

Note that recurrence of reflux symptoms and/or reflux oesophagitis on PPIs is closely related to status of LOS and oesophageal motility. If both are abnormal, 80% recurrence. If both are normal, 8% recurrence.
- ?medication timing and adherence
- ?Differences in PPI metabolism
- ?Residual acid reflux
- ?Non-acid reflux
- ?Reflux hypersensitivity
- ?Functional heartburn

Complications:

Oesophageal
- Erosive oesophagitis - reflux causes necrosis of mucosa
- Barrett's oesophagus - metaplastic columnar epithelium replaces stratified squamous epithelium after chronic GORD.
  - See separate topic
  - Predisposes to CA
  - No specific symptoms to allow it to be differentiated from GORD
  - Can be complicated in turn by ulcerations, strictures, haemorrhage
- Strictures
  - Occur as part of the healing process of ulcers - collagen is deposited, then contracts
  - May get symptomatic eg obstruction
  - Should be biopsied to exclude malignancy
  - Treat with dilatation and acid-suppressive therapy, majority effectively
  - Dilatation can be done with either a balloon dilator or Savary dilator
  - Refractor strictures can be treated with anti-reflux surgery or steroid injections
Extra-oesophageal
- Asthma
- Chronic laryngitis
- Laryngo-tracheal stenosis
- Chronic cough
- Etc