upper gastrointestinal cancers niraj jani, md
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Upper Gastrointestinal Cancers
Niraj Jani, MD
Division of Gastroenterology
Sinai Hospital
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Question 1
• 56 yo WM presents with new onset solid food dysphagia and weight loss. He smokes 1 PPD, weekly alcohol intake and uses antacids frequently. As his internist, you should first:
A. Order a barium esophagramB. Refer to a gastroenterologistC. Order a CT scanD. Prescribe a PPI and f/u in 6 weeks
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Question 2
• The patient’s symptoms in Q1 are most likely NOT secondary to:
A. GERD
B. Adenocarcinoma of the esophagus
C. Squamous Cell Cancer of the esophagus
D. Zenker’s diverticulum
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Esophageal Cancer
• Two types:• Squamous Cell Carcinoma (SCC)- previously the
most dominant esophageal cancer and worldwide accounts for 30-40% of esophageal ca
• Adenocarcinoma- over past two decades incidence is rising. Incidence within Barrett’s is 0.4-0.5%/yr
• Now both tumors occur with equal frequency
• Differ in tumor location, predisposing factors, prognosis and treatment
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Pathogenesis
• SCC- mutations in the cyclin D1 gene which is involved in cell cycling and cyclin-dependent kinases
• This complex phosphorylates the retinoblastoma gene (Rb) which leads to increased cell cycling
• Other abnormalities include mutations in the B-catenin/E-cadherin gene and activation of tumor angiogenesis factors (VEGF/EGF)
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Pathogenesis
• Adenocarcinoma- inactivation of the p16 gene through hypermethylation of its promoter
• This leads to increased cell cycling, genetic instability and formation of p53 mutations, aneuploidy
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Risk Factors
Epidemiology of esophageal cancer in the United States
Squamous cell Adenocarcinoma
New cases per year 6000 6000
Male-to-female ratio 3:1 7:1
Black-to-white ratio 6:1 1:4
Most common location Middle esophagus Distal esophagus
Major risk factors Smoking, alcohol Barrett's esophagus
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Esophageal Cancer and BE
• Incidence of Adenocarcinoma of esophagus is increasing- 3.2/100,000 people from 0.7/100,000 in the 1970’s
• Overall risk of adenoca in BE is 30-52 times higher than general population, however most people with BE will never develop dysplasia or cancer
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Trends in Age-adjusted Incidence Rates of Adenocarcinoma
0.1
1
10
1975 1980 1985 1990
White WomenBlack MenWhite Men
Rat
es p
er 1
00,0
00
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Clinical Presentation
• Dysphagia occurs in 90% of patients, odynophagia 50%
• Solids more problematic than liquids
• Other symptoms may include hoarseness, hematemesis, and nausea
• More advanced disease may cause feeling of “food getting stuck” or regurgitation
• Weight loss common
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Diagnosis/Staging
• Barium Esophagram- more accurate with larger lesions- may serve as initial test to w/u dysphagia
• Endoscopy with biopsies
• Endoscopic Ultrasound
• CT/PET
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Diagnosis/Staging
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Histology
Squamous Cell Cancer
Adenocarcinoma
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EUS-Esophageal Cancer
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EUS-Esophageal Cancer
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Diagnosis/Staging
• EUS- Sensitivity for T staging is 90%, N (lymph node) staging is 80%
• Limitations: cannot detect distant disease and overstages T3 lesions
• CT- T staging sensitivity 60%. Useful for detecting distant disease and T4 lesions
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Diagnosis/Staging
• PET- used with CT to create a fusion image that allows the CT image to be correlated with the nuclear scan
• Valuable in detecting nodal mets and detecting residual cancer after treatment
• Poor at T staging and for lesions less than 1 cm
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PET Scan –Esophageal Ca
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Treatment
• Chemotherapy- cisplatin based results in 42-64% response rate. Combination therapy for advanced disease
• Other agents include fluorouracil, taxanes, irinotecan
• Radiotherapy- used in combination with chemo- main benefit is relieving dysphagia by shrinking tumor
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Treatment
• Endoscopic Therapy- T1 lesions - Photodynamic therapy or EMR
• Surgery- esophagectomy (Ivor-Lewis) is primary treatment
• Overall mortality rate from procedure is 5-10%, morbidity 10% from anastomotic leakage, pulmonary problems, cardiac events
• Survival rate- 20% at 1 yr, 5% at 5 years
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Treatment
• Most beneficial in Stage I, II disease• Debate is whether pre-operative
neoadjuvant therapy affects outcome• Resectable lesions- improves survival 7-
9% at 2 years• Goal is to make pt node negative• Main Problem- 50-60% present with
incurable locally advanced or metastatic disease
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Question 3
• The most common malignancy of the stomach is:
A. Lymphoma
B. Carcinoid tumor
C. Adenocarcinoma
D. MALToma
E. GIST
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Question 4
• Primary treatment of a MALT lymphoma of the stomach is:
A. Surgical resection
B. Endoscopic Mucosal Resection (EMR)
C. Chemotherapy
D. Radiation
E. Eradication of H. Pylori
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Gastric Cancer
• 750,000 cases annually. 22,000 new cases in the US each year
• Rise in cancer of the proximal stomach and GEJ
• Risk Factors: Diet, Genetics, H. Pylori infection, Pernicious anemia, Pts with partial gastrectomy, Atrophic gastritis, Menetrier’s disease
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Risk Factors
• Dietary Factors- foods rich in nitrates, nitrites, preserved meat and vegetables
• Genetic Factors- Lynch syndrome II. Microsatellite instability (MSI) is present in up to 33% of gastric cancers
• Pernicious Anemia- auto-immune atrophic gastritis increased risk by 2-3x
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Risk Factors
• Partial gastrectomy- slightly increased risk
• Menetrier’s Disease- rugal fold hypertrophy, hypochlorhydria and protein-losing enteropathy
• Adenomatous Gastric Polyps
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Pathologic Features
• Distal cancer- H. Pylori related
• Proximal cancer- GERD/Barrett’s dz
• Chronic gastritis Atrophic Gastritis Intestinal Metaplasia Dysplasia/Cancer
• Intestinal type vs diffuse type
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Gastric Cancer
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Clinical Features
• Vague symptoms- early satiety, abdominal pain, bloating, dyspepsia, wt loss, anorexia
• GI bleeding, microcytic anemia, vomiting if GOO present
• Associated paraneoplastic syndromes- • Acanthosis Nigricans• Venous Thrombi (Trousseau’s syndrome)• Sister Mary Joseph’s node• Virchow’s node
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Diagnostic Studies
• Contrast radiograpy- may be initial test for vague symptoms
• Endoscopy
• CT- cannot determine depth of invasion. Good for detecting distant disease
• EUS- more accurate and T and N staging than CT
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Staging/Prognosis
• Early gastric cancer- 5-yr survival rate of 80-90%
• Survival for Stage III or IV disease is 5-20% at 5 years
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Treatment
• Surgical resection and lymph node removal are the only chance for cure
• 66% of patients present with advanced disease that is incurable by surgery alone
• Resistant to radiotherapy- used mostly for palliation
• Chemo- decreases tumor burden in 15% of patients at best
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Gastric Cancer
• Gastric Lymphoma- most of B-cell origin
• Primary gastric lymphoma rare
• Non-Hodgkin’s most common type
• 5 year survival rate is 50%
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MALTomas
• Low grade B-cell lymphoma associated with chronic H. Pylori infection
• EUS is most reliable method for staging
• Treatment of H. Pylori eradicates the tumor
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Other Gastric Tumors
• Carcinoid Tumors- 0.3% of all gastric tumors. Produce 5-HIAA and can cause carcinoid syndrome. May lead to hyper-gastrinemia
• GIST- originate usually from the muscularis propria- need to differentiate from leiomyoma, leiomyosarcoma, lipoma
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Other Gastric Lesions
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EUS-Stomach
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Small Bowel Cancers
• Adenocarcinoma- know about FAP, HNPCC
• Lymphomas- especially in AIDS pt
• Crohn’s disease
• Celiac disease
• Neuroendocrine tumors
• Gardner’s, Peutz-Jegher’s, Juvenile Polyposis syndrome, Cowden disease