Howden - GERD

Question 1

What are most common symptoms of GERD?

Answer 1

• Heartburn: burning, retrosternal discomfort (experienced in the chest, NOT the abdomen)
  1. Can be, and usually is, chronic
• Regurgitation: effortless movement of fluid up into the chest, and even into the back of the throat

Question 2

What do you see here?

Answer 2

• Erosive esophagitis: pretty much makes the dx of GERD, but most pts will have a normal-appearing esophagus
  1. 90-95% specific to GERD: clinical standard for excluding other causes
  2. Only 20-60% of pts w/acid esophageal reflux via pH testing are found to have endoscopic findings consistent with esophagitis
• Compare to normal (attached here): white, grey
• NOTE: there is an LA grading system for severity (from A being least severe to D, or most severe)

Question 3

What are some more severe symptoms of GERD?

Answer 3

• Weight loss
• Dysphagia
• Vomiting

Question 4

What questions might you ask a pt who is not responding well to PPI tx for GERD?

Answer 4

• What symptom(s) does he have?
• Was the diagnosis of GERD correctly established before PPI treatment was begun?
• Was there an initial response to the PPI?

Question 5

How can pts optimize PPI administration?

Answer 5

• Generally, best taken BEFORE FOOD
• Should be taken on a regular, ONCE DAILY basis
• Although many pts are on twice-daily PPI therapy for GERD, this is often unnecessary

Question 6

Which pts with GERD should be referred to a gastroenterologist?

Answer 6

• Pts with atypical symptoms
• Pts with unresponsive symptoms (to PPI)
• Pts w/alarm features: need to take adequate history
  1. Change in the nature of chronic symptoms
  2. Dysphagia, vomiting, unexplained weight loss, family hx of cancer, concerns about cancer, anemia
• Pts with typical chronic GERD symptoms, but no prior endoscopy (maybe – if it has been years)

Question 7

65-yo man with 10-yr hx of chronic GERD. Smoker. Takes PPI. Endoscopy 10 years ago w/grade B esophagitis. What should you do?

Answer 7

• Advise to take PPI each morning before eating
• Advise to stop smoking (not really evidence that stopping smoking does anything, but still advise pts to do so)
• See gastroenterologist -> repeat upper endoscopy to evaluate erosive esophagitis, verify no Barrett’s or cancer

Question 8

What histo changes are associated with reflux?

Answer 8

• Eosinophils: can have lymphs and neutros too
• Basal cell hyperplasia due to chronic irritation
• Elongated lamina propria papillae
• Edema/spongiosis
• Subepithelial vascular dilatation

Question 9

What is the difference b/t these 2 images?

Answer 9

• LEFT: normal
• RIGHT: gastroesophageal reflux
  1. Sm # of intraepithelial eosinophils
  2. Basal cell thickening due to chronic irritation (INC production)
  3. Lengthening of stromal papillae

Question 10

Can weight loss help relieve GERD symptoms?

Answer 10

• Dietary modification doesn’t contribute a great deal in GERD, unless the patient is overweight or obese (or if pt notes a distinct trigger to their symptoms, e.g., pts with EoE)

Question 11

When should tx be initiated in pts w/typical GERD symptoms? By whom?

Answer 11

• In pts with typical symptoms and no alarm features, treatment can and should be initiated in the primary care setting
• Primary care physicians are very comfortable doing this

Question 12

What is the role of endoscopy in patients with typical symptoms?

Can medical treatment be safely initiated before (or without) endoscopy?

Answer 12

• No urgent need for endoscopy in pts with typical symptoms -> medical tx can be safely initiated w/o endoscopy
• Reserve specialist referral (endoscopy) for pts with:
  1. Atypical/unusual symptoms
  2. Poorly responsive symptoms
  3. Alarm features: dysphagia, unexpected weight loss, family history of cancer, etc.
  4. Requirement for Barrett’s screening: reflux symptoms for >5 yrs. w/o endoscopy should probably have one

Question 13

What is the (limited) role of endoscopy in GERD?

Answer 13

• Might confirm diagnosis of GERD
  1. Good specificity: erosive esophagitis (90-95%)
  2. Poor sensitivity (most pts will not have erosions)
• Can evaluate some other symptoms, e.g. dysphagia
• Can help to rule out other conditions
  1. Ex: eosinophilic esophagitis (which can only be diagnosed by endoscopy and biopsy)
• Screening for Barrett’s esophagus

Question 14

What is going on here?

Answer 14

• Eosinophilic esophagitis (EoE): predominantly in young male patients
• Hx of atypical heartburn, intermittent dysphagia, and recurrent food impaction
• Ringed appearance to esophagus (trachealization)
• Linear furrows and narrow caliber lumen
• Eosinophilic infiltrate on biopsy; white spots are micro-abscesses filled w/eosinophils
• May respond to PPI’s (first-line) or may need topical steroids (if don’t respond to PPI’s)
• NOTE: this is a spectrum of disease -> overlap b/t EoE and GERD

Question 15

What is the difference b/t these 2 images? Arrow?

Answer 15

• LEFT: reflux
• RIGHT: EoE -> can be up to 70 eosinophils per high-power field (HPF; cut-off 20)
  1. Can get micro-abscesses of eos (arrow)
  2. Overlap w/reflux (edema, basal hyperplasia), but usually >20 eos per HPF, and usually affects the entire esophagus

Question 16

What is the role of diet in EoE?

Answer 16

• Some people treat this with elimination diets
• 6 most common foodstuffs that cause this: milk, soy, wheat, egg, peanut, and seafood

Question 17

What is Barrett’s esophagus? Epi? Dx?

Answer 17

• Intestinal metaplasia of distal esophagus that predisposes pt to esophageal adenocarcinoma
  1. 1 case in 300 pt-years in pts who do not have dysplasia -> most Barrett’s pts will never devo this cancer
• Male + white + obesity (poster = 65-yo, white, male w/20-yr hx of heartburn)
  1. Rare in women: esophageal adenocarcinoma also rare in F (about same risk as man getting breast cancer)
• DX: endoscopy + biopsies

Question 18

What do you see here?

Answer 18

• Barrett’s esophagus: typical endoscopic appearance
• Intestinal metaplasia with islands of normal-appearing squamous mucosa

Question 19

What do you see in this esophageal biopsy?

Answer 19

• Barrett’s esophagus: metaplastic columnar mucosa above gastroesophageal junction
• Goblet cells are diagnostic in US, but diagnosis varies from country-to-country
• Need to ensure biopsy is all from esophagus, and NOT from stomach

Question 20

Describe the dysplasia in these two esophageal biopsies. How are they different?

Answer 20

• LEFT: low-grade dysplasia (goblet cells)
  1. Hyperchromasia, INC N:C ratio (arrow) + start to lose polarity (nuclei no longer at basal side of epithelium)
  2. Normal glandular epi on right (arrowhead)
• RIGHT: high-grade dysplasia (abnormal gland architecture; almost a carcinoma in situ)
  1. Failure of epi cells to mature as they migrate to the esophageal surface
  2. Abnormal architecture: glands start to blend together
  3. Nuclear hyperchromasia
  4. INC nuclear to chromatin ratio
  5. Abnormal mitoses
• NOTE: p53 a major player in progression

Question 21

What do you see in this esophageal biopsy? Arrow?

Answer 21

• Abrupt transition from Barrett metaplasia (left) to low-grade dysplasia (arrow)
• Note the nuclear stratification and hyperchromasia
• Looks almost like a tubular adenoma of the colon

Question 22

What is going on in this esophageal biopsy?

Answer 22

• High-grade dysplasia: architectural irregularities, including gland-within-gland, or cribriform, profiles
• Cribriform: anatomical structure pierced by numerous small holes, in particular the plate of the ethmoid bone through which the olfactory nerves pass

Question 23

What are the risk factors for esophageal adenocarcinoma? Protective factors?

Answer 23

• RISK FACTORS: most cases arise from Barrett’s esophagus
  1. Obesity
  2. Tobacco
  3. Irradiation
• PROTECTIVE: fresh fruits and veggies
  1. Some H. pylori infections assoc w/DEC risk (if they affect gastric corpus and cause atrophy and reduced acid secretion) -> DEC reflux

Question 24

What is a major prognostic indicator for esophageal adenocarcinoma?

Answer 24

• Penetration into the submucosal lymphatic vessels
  1. By the time symptoms appear, usually already happened (even though this can take awhile) -> overall 5-yr survival at advanced stage <25%
• In contrast, 5-year survival approximates 80% in the few patients with adenocarcinoma limited to the mucosa or submucosa

Question 25

What is the going on in these two images?

Answer 25

- LEFT: adenocarcinoma -\> usually distal and, as in this case, involves the gastric cardia - RIGHT: squamous cell carcinoma -\> most frequently found in mid-esophagus, where it commonly causes strictures

Question 26

What is the difference b/t these two images?

Answer 26

- LEFT: adenocarcinoma -\> invasive here, with _glands_ all the way down to the muscle - RIGHT: squamous cell carcinoma -\> keratinizing cells (pearls), intercellular bridges (another image attached here)

Question 27

What are the epi and risk factors for SCC of the esophagus?

Answer 27

- EPI: adults \>age 45 1. M 4x more frequently than F 2. 8x more in AA - RISK FACTORS: alcohol and tobacco use, poverty, caustic esophageal injury, _achalasia_ 1. Previous radiation to mediastinum: 5-10 or more years after exposure 2. Pocket of extremely high esophageal SCC incidence in W Kenya linked to traditional fermented milk (mursik), which contains the carcinogen acetaldehyde (young men)