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Mechanistic Deep Dive
LES Anatomy + Function
- Intrinsic (LES smooth muscle) + extrinsic (diaphragm crura)
- Coordinated relaxation during swallowing
- TLESRs occur 4-8 times per hour normally
- Hiatal hernia impairs barrier
Pepsin in Esophagitis
- Active at acidic pH
- Damages esophageal mucosa
- Causes inflammation
Barrettâs Pathogenesis
- Chronic acid exposure â cellular changes
- Specialized intestinal metaplasia (goblet cells with mucin)
- CDX2 transcription factor activation
- Progression to dysplasia â adenocarcinoma
Achalasia Pathophysiology
- Loss of inhibitory neurons (myenteric plexus)
- LES fails to relax
- Absent peristalsis
- Etiology: autoimmune, post-viral, idiopathic
Recent Trials & Updates
LIBERTY-EoE-TREET (2022) â Dupilumab for EoE
- FDA approval 2022
- â Eosinophil count + symptoms
- For ⥠12 yo, refractory to PPI
KEYNOTE-590 (2021) â Pembrolizumab Esophageal Cancer
- First-line for advanced esophageal
- Both SCC + adenocarcinoma
- â OS
CheckMate 577 (2021) â Adjuvant Nivolumab
- Post-chemoradiation/surgery for esophageal/GEJ cancer
- â DFS
Vonoprazan FDA 2022 + 2024
- 2022: H. pylori treatment
- 2024: erosive esophagitis
POEM Long-Term Data
- Comparable to Heller myotomy
- Less invasive
- Risk of GERD post-POEM
Cendakimab + Tezepelumab for EoE
High-Yield Specialist Points
Functional Heartburn Treatment
- TCAs (amitriptyline)
- SSRIs
- Gabapentin / pregabalin
- CBT
Reflux Hypersensitivity
- Symptomatic without pathologic acid exposure
- Visceral hypersensitivity
- Pain modulators
PPI Side Effects (Long-Term)
- B12 deficiency
- Hypomagnesemia
- C. diff
- Hip fracture (debated)
- Pneumonia (mild â)
- CKD (controversial, observational)
- Gastric polyps
- Recommend: lowest effective dose; step-down
Anti-Reflux Surgery Selection
- Refractory or PPI-intolerant
- Hiatal hernia + symptoms
- Pre-op manometry to exclude motility disorder
- Considerations: dysphagia post-op, gas-bloat
LINX Device
- Magnetic beads encircling LES
- Allows swallowing + reflux barrier
- Less side effects than Nissen
- MRI compatibility considerations
TIF (Transoral Incisionless Fundoplication)
- Endoscopic
- Less invasive
- Mixed long-term outcomes
Achalasia Type III
- Spastic
- POEM preferred over Heller (better outcomes for type III)
Pseudoachalasia
- Malignancy at GEJ mimics achalasia
- Older onset
- Rapid weight loss
- Workup: CT, EUS, biopsy
Esophageal Manometry
- High-resolution manometry (HRM) standard
- Chicago Classification 4.0 (2020)
- Distinguishes motility disorders
Eosinophilic Esophagitis Diet
- 6-food elimination (cow milk, wheat, egg, soy, peanut/tree nut, seafood)
- Less restrictive 4-food or 2-food approaches
- Add back one at a time with EGD
Barrettâs Screening Recommendations
- High-risk: ⥠50 yo, GERD ⥠5 yr, male, white, central obesity, smoker, family history
- ACG, AGA guidelines
Esophageal Cancer Lymph Node Mapping
- Multiple levels
- Important for staging
- EUS-FNA
Endoscopic Therapy Stages
- T1a (mucosal): EMR or ESD curative
- T1b (submucosal): often requires esophagectomy (deeper invasion)
- More advanced: multimodal
Palliation
- Stenting for dysphagia
- PEG tube for nutrition
- Pain management
- Hospice
Caustic Esophageal Injury
- Alkali: deep penetrating
- Acid: superficial
- Severity assessment with endoscopy
- Avoid gastric lavage
- Long-term: stricture, cancer risk
Pearls
- GERD: TLESRs main mechanism; PPI first-line
- Vonoprazan (PCAB): newer; faster + more sustained acid suppression
- Barrettâs: surveillance + RFA for dysplasia; lifelong PPI
- EoE: dysphagia + food impaction; ⥠15 eos/HPF; dupilumab (LIBERTY-EoE) FDA 2022
- Achalasia: bird beak + manometry; POEM/Heller/dilation
- Esophageal cancer: smoking + alcohol (SCC) vs GERD + Barrettâs (adeno)
- KEYNOTE-590: pembrolizumab + chemo for esophageal cancer
- CheckMate 577: adjuvant nivolumab