Upper Gastrointestinal Cancers

Niraj Jani, MD

Division of Gastroenterology

Sinai Hospital

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

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

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

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)

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

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

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

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

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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

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

Diagnosis/Staging

Histology

Squamous Cell Cancer

Adenocarcinoma

EUS-Esophageal Cancer

EUS-Esophageal Cancer

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

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

PET Scan –Esophageal Ca

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

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

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

Question 3

• The most common malignancy of the stomach is:

A. Lymphoma

B. Carcinoid tumor

C. Adenocarcinoma

D. MALToma

E. GIST

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

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

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

Risk Factors

• Partial gastrectomy- slightly increased risk

• Menetrier’s Disease- rugal fold hypertrophy, hypochlorhydria and protein-losing enteropathy

• Adenomatous Gastric Polyps

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

Gastric Cancer

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

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

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

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

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%

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

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

Other Gastric Lesions

EUS-Stomach

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