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Gastric Cancer

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From AJCC Cancer Staging Manual, 6th ed. New York, Springer-Verlag, 2001. M1. Any N ... Peritoneal mets palpable by rectal exam (Blumer's shelf) ... – PowerPoint PPT presentation

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Title: Gastric Cancer


1
Gastric Cancer
  • Ahmet Kilic
  • October 12, 2005
  • UMMS Surgical Resident Conference

2
Gastric Neoplasia
  • Benign
  • Gastric polyps
  • Ectopic pancreas
  • Malignant
  • Gastric Adenocarcinoma
  • Gastric Lymphoma
  • Gastric Sarcoma

3
Gastric Cancer
  • Epidemiology
  • Risk Factors
  • Pathology
  • Clinical Presentation
  • Preoperative Evaluation
  • Staging
  • Treatment
  • Outcomes
  • Surveillance

4
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

7
Borrmann System
8
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

9
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

13
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

14
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

15
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

18
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

19
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

22
Surgical Treatment
  • Cardia / proximal 35-50 of gastric
    adenocarcinomas
  • Proximal
  • More advanced at presentation
  • Curative resection is rare
  • Total gastrectomy or proximal gastric resection

23
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

24
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

27
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

28
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)

29
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

30
Outcomes
31
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

32
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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39
Gastric Lymphomas
  • Epidemiology
  • Pathology
  • Evaluation
  • Staging
  • Treatment

40
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

41
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

42
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

43
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

44
Burkitts Lymphoma
  • EBV virus
  • Highly aggressive
  • Younger population
  • Cardia / body of stomach (rather than antrum)

45
Staging
  • Controversial
  • TNM like gastric adenocarcinoma

46
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

47
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

48
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

49
Gastric Sarcoma
  • Epidemiology
  • Pathology
  • Staging
  • Clinical Manifestation / Evaluation
  • Treatment

50
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

51
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

52
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,

53
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

54
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

55
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

56
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

57
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

58
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

59
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

60
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

61
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

62
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

63
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

64
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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