Gastric Adenocarcinoma

In 1879, Jules Emile Pean performed the first gastric resection for cancer. The first partial gastrectomy occurred in 1881 and was by Theodor Billroth.

Etiology

  • Genetic syndromes
    • Hereditary diffuse gastric cancer
    • Lynch syndrome
    • Familial adenomatous polyposis
    • MUTYH-associated polyposis
    • Peutz-Jeghers syndrome
    • Li-Fraumeni syndrome
  • Risk factors
    • H. pylori (most common)
    • Smoked meats, pickled foods, high sodium
    • Tobacco
    • Blood type A
    • Chronic gastritis and pernicious anemia
    • Epstein-Barr virus

Epidemiology

  • Male predominance (60%)
  • Seventh decade
  • Higher associated mortality in
    • African Americans
    • Asian Americans
    • Hispanics

Pathogenesis

  • Four genomic subtypes
    • EBV-infected tumors
    • Microsatellite unstable (MSI-high) tumors
    • Genomically stable tumors
    • Chromosomally unstable tumors

Presentation

  • Nonspecific
    • Abdominal pain
    • Nausea, vomiting
    • Anorexia
    • Dyspepsia
    • Acid reflux
    • Fatigue 
    • Weight loss
    • Early satiety
    • Anemia
    • GI bleeding
  • Metastatic disease
    • Cachexia
    • Jaundice
    • Ascites
    • Hepatomegaly 
  • Classic symptoms (that are rarely present) → advanced metastatic disease
    • Virchow’s node
    • Sister Mary Joseph’s periumbilical node
    • Blumer’s shelf: peritoneal metastasis in pouch of Douglas on rectal exam
    • Krukenberg tumor: ovary metastasis

Workup

  • Flexible upper endoscopy
    • Establishes the diagnosis most easily
    • More costly
    • Localizes primary tumor and helps with surgical planning
      • Siewert-Steini classification (1996)
        • Type I: distal esophagus 1-5 cm above GEJ
        • Type II: cardia up to 1 cm above and 2 cm below GEJ
        • Type III: subcardial 2-5 cm below GEJ
    • Can biopsy during evaluation
      • Benign ulcers: round/oval shape with smooth rim that projects beyond lumen
      • Malignant ulcers: irregular shape with associated mass that projects inside lumen 
    • More sensitive and specific for gastric cancer than any radiographic study
  • Double contrast upper GI
    • May be better to diagnose linitis plastica than flexible upper endoscopy
  • Biopsy
    • Sensitivity 70% (single biopsy)
    • Sensitivity 98% (seven biopsies)

Staging

  • Physical exam
  • Lab studies
  • H. pylori status
  • Endoscopy with EUS staging and biopsy
    • More accurate to evaluate T stage
    • Recommended in treatment guideline as part of pretreatment staging of gastric cancer in patients who have no evidence of metastatic disease
  • CT C/A/P ± PET
    • CT evaluates for distant metastasis to lungs, liver, peritoneum, or lymph nodes
    • CT is less accurate in T stage is 60%
    • Resectable → T1 tumor → resection with EMR or partial gastrectomy
    • T2-4 or N+ tumors → laparoscopy with cytology ± J-tube
  • Diagnostic laparoscopy
    • Skip if T1a
    • Stage ≥T1b prior to gastrectomy or perioperative chemoradiation
    • Prior to preoperative chemotherapy
    • Presence of GE-junction tumor or tumor involving entire stomach
    • Lymphadenopathy ≥1 cm

Treatment

  • Immediate resection
    • Indications
      • Early stage (T1/T2 N0) gastric cancers
      • Immediate palliation of bleeding 
      • High-grade tumor-associated luminal obstruction
    • Should undergo adjuvant chemotherapy if T3/T4 and/or node-positive
  • Staging laparoscopy
    • All gastric cancers of clinical tumor stage T1b or greater
    • Peritoneal carcinomatosis is a common pattern of metastasis and CT scans have a low sensitivity for detecting this
    • Peritoneal washings for cytology should be obtained
  • Locoregionally advanced gastric cancers → perioperative chemotherapy with four cycles of FLOT (5-Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel) delivered before and after surgery
  • Resectable gastric cancer
    • Approach
      • T1a (superficially invasive) → endoscopic mucosal resection or wedge excision +/- SLNB
      • Proximal tumor → total gastrectomy (reconstruct with Roux-en-Y)
      • Distal tumor → distal gastrectomy (reconstruct with Roux-en-Y or Billroth II)
    • Margins: 4-6 cm
    • Residual disease
      • R0 → no residual disease
      • R1 → microscopic residual disease
      • R2 → gross residual disease
    • Lymph node dissection
      • D1
        • Gastrectomy, resection of greater and lesser omenta
        • Resection of perigastric nodes
        • Stations 1-7
      • D2
        • D1 + named vessels of celiac axis (common hepatic, left gastric, celiac, and splenic arteries)
        • Stations 1-12; generally recommended
      • D3
        • D1 + D2 + periaortic nodes (porta hepatis nodes and those adjacent to aorta)
        • Stations 1-16; no survival benefit
  • Chemotherapy
    • Neoadjuvant: ≥T2 or N1
    • Adjuvant: ≥T3 or N1
      • FLOT: 5-Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel
      • CAPOX: Capecitabine, Oxaliplatin
      • FOLFOX: 5-Fluorouracil, Leucovorin, Oxaliplatin
      • ECF: Epirubicin, Cisplatin, 5-Fluorouracil

Relevant Information

  • Metastases
    • Sister Mary Joseph nodule: metastasis to umbilicus – suggests carcinomatosis
    • Krukenberg tumor: metastasis to ovary
    • Virchow node: metastasis to supraclavicular node
    • Irish nodule: metastasis to left axilla
  • Complete, margin-negative (R0) resection is only potentially curative surgical option for gastric adenocarcinoma
  • Per AJCC guidelines, accurate staging requires at least 16 lymph nodes in order to assess N stage
  • Postoperative surveillance
    • H&P, basic labs, and CT every 3-6 months for 1-2 years followed by 
    • H&P, basic labs, and CT every 6-12 months until 5 years out from treatment
    • Recurrence usually presents within first 4-5 years and is treated with two drug chemotherapy regimens as first-line

Borrmann Classification (1926)

  • Type I: polypoid
  • Type II: fungating lesion
  • Type III: ulceration
  • Type IV: diffusely infiltrating (linitis plastica)
    • Diffuse-type gastric cancer
    • Difficult to diagnose endoscopically as the tumors originate and spread in submucosa which can make the mucosa biopsies falsely negative
    • Tumors originate and spread within submucosa

Lauren Classification (1965)

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