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

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
  • 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

Workup

• Flexible upper endoscopy
  • Establishes the diagnosis most easily
  • More costly
  • Localizes primary tumor
  • 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 T2 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-FU, 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: perigastric nodes (stations 1-6)
    • D2: common hepatic, left gastric, celiac, and splenic arteries (stations 7-11; generally recommended)
    • D3: porta hepatis nodes and those adjacent to aorta (stations 12-16; no survival benefit)
• Chemotherapy
  • Neoadjuvant: ≥T2 or N1
  • Adjuvant: ≥T3 or N1

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

Lauren Classification

• 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

Resources

• Current management of gastric adenocarcinoma: A Narrative Review (Journal of Gastrointestinal Oncology – 2023)
• Stomach Cancer (American Cancer Society)