Upper Gastrointestinal Cancers

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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
• Order a barium esophagram
• Refer to a gastroenterologist
• Order a CT scan
• Prescribe a PPI and f/u in 6 weeks

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Question 2

• The patients symptoms in Q1 are most likely NOT
  secondary to
• GERD
• Adenocarcinoma of the esophagus
• Squamous Cell Cancer of the esophagus
• Zenkers 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 Barretts 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 31
  71
• Black-to-white ratio 61
  14
• 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 1970s
• 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
Rates per 100,000
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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
• Surgical resection
• Endoscopic Mucosal Resection (EMR)
• Chemotherapy
• Radiation
• 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, Menetriers
  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
• Menetriers 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/Barretts 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 (Trousseaus syndrome)
• Sister Mary Josephs node
• Virchows 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-Hodgkins 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
• Crohns disease
• Celiac disease
• Neuroendocrine tumors
• Gardners, Peutz-Jeghers, Juvenile Polyposis
  syndrome, Cowden disease