Esophagus and GI Cancer

Question 1

Describe the histology of Esophageal and GI cancers.

Answer 1

• Esophageal cancer
  
  • Squamous cell: cells lining the esophageal lumen
  • Adenocarcinoma: columnar cells that form glands
• Gastric cancer
  
  • Adenocarcinoma
    
    • Intestinal
    • Diffuse

Question 2

Differentiate between intestinal and diffuse type gastric cancers.

Answer 2

• Intestinal: cohesive neoplastic cells that form glands and tubular structures (associated with intestinal metaplasia)
• Diffuse: discohesive cells that invade individually
  
  • may lead to linitis plastica (associated with mucin production and signet rings)
  • linitis plastica is where the stomach can’t stretch, so sense of fullness is quickly achieved with meals

Question 3

What are the major risk factors for esophageal cancer?

Answer 3

• Either histology (SCC and adenocarcinoma)
  
  • Tobacco (9x increase for SCC, 4x increase for AC)
  • Smokeless tobacco
  • Mediastinal radiotherapy
• Squamous cell cancer
  
  • Tobacco (9x increase)
  • Alcohol (5x increase)
  • Both leads to a 20x increase!
  • A diet low in fruit and vegetables
  • Medical conditions
    
    • Tylosis
    • Plummer-Vinson syndrome
    • Achalasia
    • Celiac disease
    • HPV

Question 4

What is Barett’s esophagus and what is its role in esophageal cancer?

Answer 4

• Barrett’s esophagus is the acquired metaplasia of the transition zone between the squamous epithelium of the esophagus and the columnar cells of the stomach
  
  • GERD
  • achalasia
  • chemical injury
  • hiatal hernia
  • connective tissue disease
  • genetic factors
• Clinical risk factors for Barretts metaplasia and adenocarcinoma
  
  • Male
  • Obese
  • > 45 years of age
  • Drug therapy (beta-ag, benzo)
  • > 8 cm of Barretts
  • H pylori absent
  • GER > 3 times/week
  • Heavy tobacco
  • GER for > 10 years
  • Mucosal damage
  • White
  • Low fruit and veg diet

Question 5

What are the risk factors for gastric cancer?

Answer 5

• Universal demographic factors
  
  • Increasing age
  • Male sex
  • Deprivation
• Environmental factors
  
  • H. Pylori
  • Medical disease
  • Tobacco
  • Stomach surgery
  • Diet
  • Blood group A
  • Occupation
  • Medications
  • Radiation
  • BMI
  • Alcohol
  • Age at menopause

Question 6

What is H. pylori and its pathogenesis?

Answer 6

• Gram negative microaerophilic bacterium
  
  • Acquired in childhood
  • Highest in developing world, decreasing in developed world
  • Infection
    
    • Inflammation
    • Chronic infection
    • Chronic gastritis, atrophic gastritis, gastric atrophy
    • Loss of HCl, pepsin, intrinsic factor

Question 7

How does H. pylori increase risk for gastric cancer?

Answer 7

• Loss of infection with onset of cancer
  
  • H pylori does not colonise areas of cancer, intestinal metaplasia, or atrophy
• There is evidence that with the development of advanced gastric disease the organism can be lost from the stomach
• An overall odds ratio (OR) of around three was shown for non-cardia stomach cancer
  
  • OR of around six for those who were tested for H. pylori ten or more years prior to the development of stomach cancer
  • Infection with cytotoxin CagA-positive H. pylori carries a higher risk than infection with CagA-negative strains

Question 8

What are the common methods of workup for esophageal cancer?

Answer 8

• T-stage: EUS
  
  • dysphagia generally corresponds to T3
• N-stage: EUS, PET
  
  • mediastinal, celiac, not peritumoral
• M-stage: CT/MRI
  
  • not accurate for distant lymph nodes

Question 9

What are the most important aspects of treatment planning for esophageal cancer?

Answer 9

• 3 modalities for therapy
  
  • Chemotherapy
  • Radiation
  • Surgery
• Factors to consider in treatment planning
  
  • Stage of disease
  • Performance status
  • Medical co-morbidites
  • Goals of care

Question 10

What is the role of surgery in esophageal cancer?

Answer 10

• Only complete microscopic resection is curative
• Cervical and suprabifurcal
  
  • less likely to have complete resection
• No correlation with extent of lymphadenectomy
  
  • 2 field: abdominal and mediastinal
  • 3 field: cervical, mediastinal and abdominal
• Transthoracic or abdominal approach equivalent
• Correlation with surgical experience

Question 11

What is the role of surgery in gastric cancer?

Answer 11

• Subtotal: proximal or distal if 5 cm margin
• Total gastrectomy for all others
• Pancreatectomy and splenectomy increases complications
• D1-D4 lymph node dissection
  
  • D1 lesser and greater curvature, paracardial
  • D2 gastric, hepatic, celiac, splenic
  • D3 hepatoduodenal
  • D4 retropancreatic, root of mesentary, transverse mesocolon, paraaortic

Question 12

What is the mechanism of trastuzumab?

Answer 12

• Inhibits HER2-mediated signalling in HER2-positive tumors
• Prevents HER2 activation by blocking extracellular domain cleavage
• Activates antibody-dependent cellular cytotoxicity

Question 13

What is TNM staging for esophageal cancer?

Answer 13

• Tis
  
  • High grade dysplasia
• T1
  
  • Invades submucosa
• T2
  
  • Invades muscularis propria
• T3
  
  • Invades adventitia
• T4
  
  • Invades adjacent structures
• T4a
  
  • Resectable (pleura, pericardium, diaphragm)
• T4b
  
  • Unresectable (aorta, vertebral body, trachea)
• N0
  
  • No regional lymph nodes involved
• N1
  
  • 1-2 positive regional lymph nodes
• N2
  
  • 3-6 positive regional lymph nodes
• N3
  
  • ≥ 7 positive regional lymph nodes
• M0
  
  • No metastases
• M1
  
  • Distant metastases

Question 14

What is TNM staging for gastric cancer?

Answer 14

• Tis
  
  • Intraepithelial without invasion of the lamina propria
• T1
  
  • Invades lamina propria or submucosa
• T2a
  
  • Invades muscularis propria or subserosa
• T2b
  
  • Invades subserosa
• T3
  
  • Penetrates serosa (visceral peritoneum)
• T4
  
  • Invades adjacent structures (spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal, kidney, small intestine, retroperitoneum)
• N0
  
  • No regional lymph node metastases
• N1
  
  • 1-6 regional lymph nodes involved
• N2
  
  • 7-15 regional lymph nodes involved
• N3
  
  • > 15 regional lymph nodes involved