Esophageal, Gastric, and Pancreatic Neoplasia Flashcards
Recognize and name the different pathologic subtypes of esophageal cancer.
Squamous cell
o Previously the majority of cases
Adenocarcinoma
o Fastest growing cancer over past 4 decades (especially in Caucasians)
Describe the risk factors for the different subtypes of esophageal cancer.
For squamous cell: Chronic inflammatory irriation “Field cancerization effect” when used together increases risk • Smoking • Alcohol • Lye ingestion • HPV infection • HNSCC Other dietary factors Male gender (2-4x more likely) Age African Americans (4-5x increased risk)
For adenocarcinoma:
o Male gender
o Obesity
o Chronic GERD
Barrett esophagus:
• Metaplastic precursor lesion
• Columnar epithelium with goblet cells replace normal squamous epithelium in distal esophagus
• Visible endoscopically (see salmon-colored muscoas with paler, normal epithelium)
“Intestinal Metaplasia” on biopsy
• Progressing to low grade or high grade dysplasia
• High grade dysplasia increases risk of conversion to malignancy to 10-30% per year
• So = treat like cancer
Management:
• Acid suppression (chronically)
• Weight loss (minimize reflux)
• Frequent surveillance endoscopy with biopsy
• Endoscopic interventions for dysplasia
Understand the changing epidemiology regarding esophageal cancer in light of the change in modifiable risk factors.
7th most common cancer death among U.S. males
Up to 400K deaths/year worldwide
o Especially in developing countries (highest in East Asia and East Africa)
o “Esophageal cancer belt” = from Iran to North Central China
o Primarily squamous cell type
o Due to high prevalence of smoking, ingestion of really hot beverages, poor nutrition
Esophageal cancer: clinical presentation
o Dysphagia (most common) and regurgitation
• With any risk factor → evaluation with endoscopy
o Reflux
o Weight loss
o Midback discomfort
o Bleeding/melenic stools (dark, tarry, odorous)
o Later signs: skeletal complications (bony metastases), jaundice (liver metastases)
Esophageal cancer: Diagnosis
Upper endoscopy with biopsy
• Pathology for adeno- or squamous carcinoma
Endoscopic ultrasound
• Evaluate extent of nodal disease (staging)
CT, PET/CT
• Evaluate for any metastatic disease
Staging = essential
• Use the TNM system:
• Stage 1: (small primary) = 5 year survival of ~70%
• Stage 2: (bigger primary, no nodes) = 45-50%
• Stage 3: (nodes) = 20%
• Stage 4: (metastatic disease) = <5%
Describe the incidence and risk factors for developing gastric cancer, including regions of the world where gastric cancer may be endemic.
Incidence: o Primarily adenocarcinoma o In U.S. = relatively rare o In developing world = higher rates • Ex: East Asia (Japan, China, Mongolia, Russian Federation)
Risk factors: o H. pylori = 2-6x risk o High salt, high nitrate foods, poorer food preparation o Atrophic gastritis o Low SES Familial syndromes: • Hereditary Diffuse Gastric cancer • Truncating mutation in CDH1 → inactivates e-cadherin • Lifetime risk of gastric cancer: 83% • More often diffuse histology • Earlier median age (38 years) • May be associated with other malignancies (ex: breast cancer)
Gastric Cancer: subtypes
Intestinal • More mass-like • Intraluminal • Prone to bleeding • Higher association with H. pylori
Diffuse • Often submucosal • Presenting complaint = early satiety • More often presents at late stage • Thought to be more aggressive
Gastric Cancer: clinical presentation
o Frequently asymptomatic o Abdominal pain o Weight loss o Nausea o Bloating o Bleeding/melena o Ulcers refractory to PPI therapy or triple/quad therapy
Gastric Cancer: diagnosis
EGD (upper endoscopy) with tissue biopsy = gold standard
• Diffuse vs. intestinal
• HER-2-Neu
EUS (endoscopic ultrasound) for T stage and assessment of local nodal burden
CT/PET for distant staging
• Since frequently presents as metastatic disease
Esophageal Cancer treatment
For localized disease:
o Careful multidisciplinary evaluation
o Most often already have T3 or greater tumor by time of presentation
o Local recurrence rates high with surgery alone
o Preoperative (neoadjuvant) treatment = Chemotherapy + radiotherapy
• About 1/3 have no evidence of tumor at surgery
Surgery to follow
• Esophagectomy with gastric pullup
• Complications:
• Can never lie flat again (have to be elevated >30°)
• Decreased appetite, early satiety, significant weight loss
For metastatic disease
o See gastric cancer below
Symptom management
For dysphagia and metastatic disease = short course radiotherapy or esophageal stenting
• Improves symptoms
• But does NOT improve survival
• Stents use lower in esophagus (because somatosensory nerves in upper → pain)
Gastric Cancer treatment
For localized disease = Surgical therapy
o Partial or total gastrectomy
o Depends on size/location of tumor
Type of lymph node dissection = debated
• D1: local nodes and adjacent omentum removed (preferred in U.S. and most of Europe)
• D2: peripancreatic, perisplenic nodes; may involve taking spleen and vascular pedicle of stomach (in areas where gastric cancer endemic)
Perioperative therapy: Chemotherapy pre-op and post-op: • Provides some tumor shrinkage • “Cleans up” micrometastatic disease • Test of time for metastases to develop Chemoradiotherapy post-op • 5-FU based chemotherapy + radiation Both approaches = improve long-term outcomes but neither is clear “winner”
For metastatic disease:
Palliative Chemotherapy: lots of different drug options
• Fluoropyrimidines, taxanes, platinums, irinotecan, anthrayclines
Targeted therapies?
• Ex: Her-2 used in breast cancer also demonstrated improved survival
Median overall survival still around 1 year (without treatment ~4-6 months)
Identify non-malignant pancreatic neoplasms.
- Intraductal papillary mucinous neoplasms (IPMNs)
- Mucinous cystic neoplasms
- Serous cystic neoplasms
Identify risk factors for pancreatic adenocarcinoma.
Adenocarcinoma = most common primary pancreatic malignancy (95%)
o About 75-80% arise in pancreatic head
o Arise from ductular epithelium
o Quickly invasive
o Intense fibrous, scar forming reaction in surrounding stroma
o Often infiltrates along nerves and vessels
More people die from pancreatic cancer in WI than breast cancer = public health problem
Risk factors: o Age (median 72 years) o Smoking o Obesity o Diabetes o Note: alcohol is NOT a risk o African-Americans have 2x risk Some familial syndromes: • BRCA2, CF, HNPCC, FAP, atypical familial mole melanoma (p16 mutation)
Pancreatic adenocarcinoma: clinical presentation
Jaundice (due to biliary obstruction) • Clay colored stools (no bilirubin in bile/GI tract) • Tea colored urine (due to urobiligen) o Epigastric pain radiating to back o New onset diabetes o Weight loss o Nausea and vomiting o Palpable gallbladder (Courvoisier sign)
Pancreatic adenocarcinoma: diagnosis
Endoscopic retrograde cholangiopancreatography (ERCP)
• Diagnostic AND therapeutic procedure
Endoscopic ultrasound
• Assess nodes and vascular pedicle for local invasion
• Visualize small lesions
CT scan with pancreatic protocol
