Gastric Cancer

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Gastric Cancer

• Ahmet Kilic
• October 12, 2005
• UMMS Surgical Resident Conference

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Gastric Neoplasia

• Benign
• Gastric polyps
• Ectopic pancreas
• Malignant
• Gastric Adenocarcinoma
• Gastric Lymphoma
• Gastric Sarcoma

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Gastric Cancer

• Epidemiology
• Risk Factors
• Pathology
• Clinical Presentation
• Preoperative Evaluation
• Staging
• Treatment
• Outcomes
• Surveillance

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Epidemiology

• 1980s most common CA worldwide
• Geography (Japan / S. America)
• United States
• 10th most common dec. incidence in past 70 years
• Male Female 21

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Pathology

• Gastric Adenocarcinoma ( 95)
• Squamous Cell Carcinoma
• Adenoacanthoma
• Carcinoid
• Gastrointestinal stromal tumors (GISTs)
• Lymphoma

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Borrmann System
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Lauren System

• Intestinal
• Environmental
• Gastric atrophy, intestinal metaplasia
• Men gt women
• Increasing inc. w/ age
• Gland formation
• Hematogenous Spread
• Microsatellite instability
• APC gene mutations
• p53, p16 inactivation
• APC, adenomatous polyposis coli

• Diffuse
• Blood type A
• Women gt men
• Younger age group
• Poorly differentiated, signet ring cells
• Transmural / lymphatic spread
• Decreased E-cadhedrin
• p53, p16 inactivation

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WHO Classification

• 5 main categories
• Adenocarcinoma, Adenosquamous cell carcinoma,
  squamous cell carcinoma, undifferentiated
  carcinoma and unclassified carcinoma
• Adenocarcinoma subdivided
• Papillary, tubular, mucinous, signet ring
• Further subdivided based on differentiation

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Clinical Presentation

• Asymptomatic
• Early
• Vague epigastric discomfort / indigestion
• Pain is constant, nonradiating, unrelieved by
  food digestion
• More advanced disease
• Weight loss
• Anorexia
• Fatigue
• Emesis
• Symptoms dependent on location
• Proximal
• Distal
• Diffuse
• GI bleeding, obstruction

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Clinical Presentation

• Physical signs late
• Assoc. w/ locally advanced or mets
• Palpable abdominal mass
• Palpable supraclavicular (Virchows) LN
• Palpable periumbilical (Sister May Josephs) LN
• Peritoneal mets palpable by rectal exam (Blumers
  shelf)
• Palpable ovarian mass (Krukenbergs tumor)
• S/Sx of hepatomegaly

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Pre-operative Evaluation

• Once gastric cancer is suspected
• Flex. Upper endoscopy modality of choice
• Double contrast barium upper gi cost effective w/
  90 accuracy however can not distinguish benign
  from malignant gastric ulcers.
• Flex. Upper Endo w/ multiple biopsies (gt7) around
  ulcer crater for histo
• Biopsy of ulcer crater ? necrotic debris
• Accuracy (98) ? inc. w/ direct-brush cytology

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Pre-operative Evaluation

• Esophagogastroduodenoscopy palliation
• Laser ablation
• Dilation
• Tumor stenting
• EUS
• Aid in staging
• gastric wall tumor invasion
• LN status

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Diagnosis Gastric Cancer

• CBC, CMP, Coags
• CXR, CT scan of abdomen
• Women
• Pelvic CT / US
• CT chest for proximal gastric cancer
• Limitations
• lt 5 mm mets on liver/peritoneum
• Staging for LN mets 25 86
• Laparoscopy
• 23 37 mets
• Cytology of peritoneal fluid / peritoneal lavage
• finding ? poor prognosis

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Staging

• TNM system
• 1997
• Nodal status
• Location ? number of positive nodes
• Cardia vs distal - ? Survival
• R status
• R0 microscopically negative margin
• R1 micro , gross
• R2 gross residual disease

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Staging
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Surgical Treatment

• Absence of distant mets
• Resection margin w/ neg. microscopic margins
• Gastric tumors char. by extensive intramural
  spread
• Line of resection at least 6 cm from the tumor
  mass to decrease recurrence at anastomosis
• App surgery based on location / pattern of spread

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Surgical Treatment

• Cardia / proximal 35-50 of gastric
  adenocarcinomas
• Proximal
• More advanced at presentation
• Curative resection is rare
• Total gastrectomy or proximal gastric resection

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Proximal / Cardia

• Proximal Gastrectomy increased morbidity /
  mortality
• Buhl, et al.
• Dumping, heartburn, reduced appetite
• Norwegian Stomach Ca Trial
• Prox. gastrectomy morbid / mortal 52 16
• Total gastrectomy morbid / mortal 38 8
• Total gastrectomy considered procedure of choice
  for proximal gastric lesions

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Distal Tumors

• Account for 35 of all gastric cancers
• No 5-year survival difference b/n subtotal vs
  total gastrectomy
• Subtotal appropriate if negative margins
• Recurrence vs nonrecurrence depends on margin of
  3.5 cm vs 6.5 cm

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Extended Lymphadenectomy

• Controversial
• Japanese system
• D1 group 1 LN
• D2 groups 1 2
• D3 D2 plus para-aortic LN
• To remove station 10 11 LN splenectomy
• D2 resection partial pancreatectomy

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Extended Lymphadenectomy

• No longer routine
• Used for tumor extension
• Removal of station 10 LN
• Dutch
• D1 vs D2 resection
• Increased intra-hosp mortality
• Japan
• D2 improved survival over D1
• West
• No improvement

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Palliation

• 20 30 of gastric cancer presents w/ stage IV
  disease
• Relief of symptoms w/ minimal morbidity
• Surgical palliation
• Percutaneous, endoscopic, radiotherapuetic
  techniques
• Nonoperative tx
• Laser recanalization, endoscopic dilatation (/-
  stent)

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Adjuvant Therapy

• 1999
• 29 of gastrectomy pts underwent some type of
  adjuvant tx (71 sx alone)
• Southwest Cancer Oncology Group trial
• 5-FU, Leucovorin w/ chemorad for R0
• Sx 27 mos 3 yr survival 41
• Chem/Rad 36 mos 3 yr survival 50

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Outcomes
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Recurrence

• After gastrectomy quite high
• 40 80
• Most occur w/in first 3 years
• Locoregional failure 38 45
• Anastomosis, gastric bed and regional nodes
• Peritoneal dissemination 54

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Surveillance

• Recurrence high first 3 years
• Complete HP every 4 mos for 1 year
• Then every 6 mos for 2 years
• Annually after
• CBC, LFT as clinically indicated
• CXR, CT abd/pel - ? Routinely
• Annual endoscopy for subtotal gastrectomy

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Gastric Lymphomas

• Epidemiology
• Pathology
• Evaluation
• Staging
• Treatment

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Epidemiology

• Stomach most common site for lymphomas in GI
  system
• Primary gastric lymphoma uncommon
• 15 of gastric CA, 2 of lymphomas
• Vague symptoms
• Epigastric pain, early satiety and fatigue
• Bleeding uncommon
• 50 have anemia on presentation
• 6th and 7th decade (MF is 21)
• Most commonly in antrum

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Pathology

• Multiple classification systems
• Most common diffuse large B-cell 55
• Extranodal marginal cell lymphoma (MALT) 40
• Burkitts lymphoma 3
• Mantel cell 1
• Follicular lymphoma 1

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Pathology

• Diffuse large B-cell
• Usually primary
• May occur from progression of less aggressive
  lymphomas (chronic lymphocytic leukemia / small
  lymphocytic lymphoma, follicular lymphoma or
  MALT)
• Risk factors
• Immunodeficiencies, H. pylori

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Gastric MALT extranodal marginal zone lymphomas
of MALT type

• Commonly preceded by H. pylori associated
  gastritis
• t(114) (p22q32) and t(1118)(q21q21)
• Impaired response to apoptotic singaling
• Increased NF-?B
• t(1118)(q21q21)
• Predicts responsiveness to tx by H. pylori
  eradication

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Burkitts Lymphoma

• EBV virus
• Highly aggressive
• Younger population
• Cardia / body of stomach (rather than antrum)

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Staging

• Controversial
• TNM like gastric adenocarcinoma

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Treatment

• Multimodality early stage
• Resection controversial
• Chemo/rads alone
• Perforation w/ chemo 5
• CHOP cyclophosphamide, hydroxy- daunomycin,
  oncovin, predinose)
• 5 year survival
• Sx/Chemo/Rad 82
• Chemo/Rad 84.4

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Treatment

• Radiation
• Limited in large tumors
• Local control 100 lt 3 cm
• 60 70 if gt 6 cm
• Risk of complications 30 at 10 years

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Treatment

• Late-stage
• Not amenable to sx chemo
• MALT/very limited diffuse large B-cell
• H. pylori eradication alone
• 75
• Repeat endo in 2 mos. biannual endo for 3 years
• Failure of above increased if
• Transmural, node , transformation Bcl-10

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Gastric Sarcoma

• Epidemiology
• Pathology
• Staging
• Clinical Manifestation / Evaluation
• Treatment

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Epidemiology

• Arise from mesenchymal components of gastric wall
• 3 of all gastric CA
• GIST most common
• Stomach (60-70)
• After 4th decade
• Mean age 60

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GIST - Pathology

• Initially thought to arise from smooth muscle
  cells previously classified as leiomyoma /
  leiomyosarcoma
• Histo
• Muscularis propria likely from cells of Cajal
• GIST
• Cellular
• Spindle cell
• Pleomorphic mesenchymal tumors
• Kit protein, CD34

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Staging

• No current system
• Prognosis
• Mitotic frequency
• Low benign High malignant
• Other signs of malignancy
• Size gt 5 cm cellular atypia, necrosis or local
  invasion, c-kit,

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Clinical

• Most common presentation
• GI bleeding, pain dyspepsia
• Endoscopy first diagnostic test
• w/ biopsy 50
• CT best since neoplasm grows intramurally
• Double-contrast UGI smooth edged filling defect

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Treatment

• Surgery
• Negative margin (en-bloc if adjacent organs)
• Avoid rupture of tumor to prevent peritoneal
  seeding
• LN mets rare (lt10) no added benefit
• Most recurrences in first 2 years
• Local disease w/ assoc. liver mets
• 5 year survival 48 (19 56)
• Adjuvant tx
• Radiation no proven benefit
• 5 respond to doxorubicin
• Glivic/Gleevec 54 partial response
• Approved fro CD117 unresectbale, mets

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Questions

• A patient has an 8 mm lesion on the lesser
  curvature of the stomach near the
  gastroesophageal junction. CT of the abdomen is
  negative. Gastric biopsy is returned as mucosal
  associated lymphoid tumor (MALToma). The most
  appropriate initial treatment would be
• A. Radical gastrectomy, roux-en-Y
  esophagojejunostomy
• B. Proximal gastrectomy, esophagogastrostomy
• C. Metastatic work-up treatment for H. pylori
• chemotherapy radiotherapy
• D. Treatment for H. pylori
• E. Wedge resection

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Questions

• A patient has an 8 mm lesion on the lesser
  curvature of the stomach near the
  gastroesophageal junction. CT of the abdomen is
  negative. Gastric biopsy is returned as mucosal
  associated lymphoid tumor (MALToma). The most
  appropriate initial treatment would be
• A. Radical gastrectomy, roux-en-Y
  esophagojejunostomy
• B. Proximal gastrectomy, esophagogastrostomy
• C. Metastatic work-up treatment for H. pylori
• chemotherapy radiotherapy
• D. Treatment for H. pylori
• E. Wedge resection

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Questions

• Regarding gastric anatomy, physiology, and
  pathology, which of the following statements is
  correct?
• A. Helicobacter pylori, a gram-negative bacteria
  that produces urease, has
• been implicated in the genesis of
  gastric carcinoma
• B. The right and left gastroepiploic arteries
  branches of the
• gastroduodenal and left gastric
  arteries, respectively are responsible
• for the blood supply of the greater
  curvature of the stomach
• C. Truncal vagotomy accelerates emptying of
  solids and delays emptying of
• liquids
• D. In patients with Zollinger-Ellison
  syndrome, the treatment of choice for
• multiple ulcers is total gastrectomy
• E. Gastric cancers are the most common
  tumors in the GI tract to present
• with sub-mucosal spreading, needing at
  least 5 cm of resection margins

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Questions

• Regarding gastric anatomy, physiology, and
  pathology, which of the following statements is
  correct?
• A. Helicobacter pylori, a gram-negative bacteria
  that produces urease, has
• been implicated in the genesis of
  gastric carcinoma
• B. The right and left gastroepiploic arteries
  branches of the
• gastroduodenal and left gastric
  arteries, respectively are responsible
• for the blood supply of the greater
  curvature of the stomach
• C. Truncal vagotomy accelerates emptying of
  solids and delays emptying of
• liquids
• D. In patients with Zollinger-Ellison
  syndrome, the treatment of choice for
• multiple ulcers is total gastrectomy
• E. Gastric cancers are the most common
  tumors in the GI tract to present
• with sub-mucosal spreading, needing at
  least 5 cm of resection margins

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Questions

• Which of the following statements about the
  clinical
• evaluation of gastric lymphoma is MOST accurate?
• A. Best diagnosed by abdominal computed
• tomographic (CT) scan with oral contrast
• B. Accounts for approximately 20 of gastric
• malignancies
• C. Usually detected by upper gastrointestinal
  endoscopy and
• biopsy
• D. Abdominal pain is an infrequent presenting
  complaint
• E. Usually presents urgently with hemorrhage,
  perforation, or
• obstruction

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Questions

• Which of the following statements about the
  clinical
• evaluation of gastric lymphoma is MOST accurate?
• A. Best diagnosed by abdominal computed
• tomographic (CT) scan with oral contrast
• B. Accounts for approximately 20 of gastric
• malignancies
• C. Usually detected by upper gastrointestinal
  endoscopy and
• biopsy
• D. Abdominal pain is an infrequent presenting
  complaint
• E. Usually presents urgently with hemorrhage,
  perforation, or
• obstruction

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Questions

• A 42 year old physician has three month
  history of dark stools, vague abdominal pain, and
  early satiety. PE demonstrates heme positive
  stool. The patient is anemic. Upper endoscopy
  shows a 4.9 cm polypoid mass located in the
  distal antrum. Endoscopic biopsies of this
  lesion are inconclusive. At exploration, a
  gastric lymphoma confined to the stomach and
  regional nodes is confirmed. The most
  appropriate management is
• A. Chemotherapy
• B. Radiation therapy
• C. Chemotherapy and radiation
• D. Curative resection
• E. Resection plus adjuvant chemoradiation

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Questions

• A 42 year old physician has three month
  history of dark stools, vague abdominal pain, and
  early satiety. PE demonstrates heme positive
  stool. The patient is anemic. Upper endoscopy
  shows a 4.9 cm polypoid mass located in the
  distal antrum. Endoscopic biopsies of this
  lesion are inconclusive. At exploration, a
  gastric lymphoma confined to the stomach and
  regional nodes is confirmed. The most
  appropriate management is
• A. Chemotherapy
• B. Radiation therapy
• C. Chemotherapy and radiation
• D. Curative resection
• E. Resection plus adjuvant chemoradiation

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Questions

• The most common symptoms present at initial
  diagnosis of gastric carcinoma are
• A. Weight loss and vague abdominal pain
• B. Ulcer-type pain and early satiety
• C. Anorexia and vomiting
• D. Melena and lower abdominal pain
• E. Nausea and dysphagia

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Questions

• The most common symptoms present at initial
  diagnosis of gastric carcinoma are
• A. Weight loss and vague abdominal pain
• B. Ulcer-type pain and early satiety
• C. Anorexia and vomiting
• D. Melena and lower abdominal pain
• E. Nausea and dysphagia

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