Internal Medicine

Gastric cancer

Cancer developing from the lining of the stomach.

Cancer developing from the lining of the stomach.


  • 4th M/C malignancy worldwide
  • 2nd M/C cancer-related deaths worldwide

↓ Incidence of gastric cancer:

  • Successful reduction of H. pylori infections
  • Changes in food preservation, such as less pickling of vegetables, and less smoking and processing of meat
  • Greater availability of fresh fruits and vegetables

Gastric cancer survival rates:

  • Earlier detection
  • Better treatment options
Bar chart of stomach cancer, age-standardized 5-year net survival, adults (aged 15–99), England and Wales, 1971–2011 | Cancer Research UK


  • Adenocarcinoma (M/C, 90%): Columnar glandular epithelium
  • Lymphoma (3-5%): B-lymphocytes (B-cells)
    • Mucosa-associated lymphoid tissue (MALT) lymphoma
    • DLBCL (diffuse large B cell lymphoma)
  • Carcinoid tumour: G-cells in stomach
  • Leiomyosarcoma: Smooth muscle cells

Lauren’s histopathologic classification (M/C):

  • Intestinal (with intercellular junctions) (M/C)
    • Mass lesions: Polyploid tumours/ulcers (glands/tubules lined by epithelium resembling the intestinal mucosa)
  • Diffuse (without intercellular junctions)
    • No mass lesions
    • Poor prognosis
Chen, YC., Fang, WL., Wang, RF. et al. Clinicopathological Variation of Lauren Classification in Gastric Cancer. Pathol. Oncol. Res. 22, 197–202 (2016).

World Health Organization (WHO) classification:

  • Adenocarcinoma
  • Signet ring-cell carcinoma
  • Undifferentiated carcinoma
Heterogeneity of histopathological classification systems in gastric cancer | Heterogeneity in Gastric Cancer: From Pure Morphology to Molecular Classifications – Scientific Figure on ResearchGate. Available from: [accessed 3 Mar, 2021]

Japanese classification:

For early gastric cancer (Cancer limited to mucosa and submucosa with/without lymph node involvement (T1 & any N)
Macroscopic classification of early gastric cancer according to the Japanese Research Society for gastric cancer. | EVERETT, S. M. and AXON, A. T. R. (1997) ‘Early gastric cancer in Europe’, Gut, 41(2), p. 142 LP-150. Available at:

Bormann classification (4 basic growth patterns):

Indiacted for advanced gastric cancer
  1. Polypoid (type I)
  2. Fungating (type II)
  3. Ulcerated (type III)
  4. Diffusely infiltrative (type IV): Linitis plastica appearance (worst prognosis)
Borrmann four-stage macroscopic classification of advanced gastric carcinoma: I: Protruding type; II: Ulcerative & localised type; III: Ulcerative & infiltrative type; IV: Diffusely infiltrative type | Clinical Gate. (2015). Epithelial Neoplasms of the Stomach. [online] Available at: [Accessed 21 Oct. 2017].

Molecular subtypes

  • Subtype 1: Microsatellite instability (MSI) (best prognosis)
  • Subtype 2: EBV associated
  • Subtype 3: Chromosomal instability (CIN)
  • Subtype 4: Genomic instability (GS) (worst prognosis)
This schematic lists some of the salient features associated with each of the four molecular subtypes of gastric cancer. Distribution of molecular subtypes in tumours obtained from distinct regions of the stomach is represented by inset charts. | Network, T. C. G. A. R. (2014) ‘Comprehensive molecular characterization of gastric adenocarcinoma’, Nature. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved., 513(7517), pp. 202–209. Available at:


Etiology is multifactorial, although infection with Helicobacter pylori is the primary cause.


  • H. pylori infection (M/C, 80% cases)
    • Gastric cancer is one of a few types of neoplasms directly linked to an infectious agent.
    • Also MALT lymphoma
    • Protective against gastro-esophageal reflux (GERD) and esophageal adenocarcinoma
  • Epstein-Barr virus (EBV) (5-16% cases)
    • ~90% in gastric lymphoepitheliomas (carcinomas with lymphoid stroma)


  • Tobacco (11% cases)
  • Moderate-high alcohol consumption (39% ↑ risk)
  • High salt diet
    • Salt erodes mucosal barrier of stomach → inflammation → ↑ gastritis and carcinogenic effects of known gastric carcinogens like N-methyl-N-nitro-N-nitrosoguanidine (MNNG)
  • Processed & smoked meat
  • Fresh fruits and vegetables ↓ incidence

Host factors:

  • Male (2x more likely)
  • Old age
  • Blood group A (20% more cases)
    • Blood group O associated with ↑ risk of peptic ulcers
  • Diet high in smoked/salty foods

Family history/hereditary (5-10% cases):

  • Hereditary familial gastric cancer:
    • Hereditary diffuse gastric cancer (HDGC)
    • Gastric adenocarcinoma & proximal polyposis of the stomach (GAPPS)
    • Familial intestinal gastric cancer (FIGC)
  • Other hereditary cancer syndromes:


Prolonged precancerous process takes place, with well-defined sequential stages:

(Initiated & sustained by infection with H pylori)

Chronic active gastritis

Chronic atrophic gastritis

Intestinal metaplasia
(Complete/small intestinal type → incomplete/colonic intestinal type

Dysplasia or intraepithelial neoplasia

Invasive carcinoma

Multifactorial pathway leading to gastric carcinoma. Many host, bacterial, and environmental factors act in combination to contribute to the precancerous cascade leading to development of gastric cancer. | Wroblewski, L. E., Peek, R. M. J. and Wilson, K. T. (2010) ‘Helicobacter pylori and gastric cancer: factors that modulate disease risk.’, Clinical microbiology reviews. United States, 23(4), pp. 713–739. doi: 10.1128/CMR.00011-10.
This cancer presented in a 40-year-old woman complaining of abdominal pain. Endoscopically it was a “very suspicious” ulcer. Biopsy showed diffusely infiltrating signet ring cell adenocarcinoma. These are gross photos of the subtotal gastrectomy specimen. The photo above is asen face view of the ulcer. The pyloric margin is to the left. The ulcer is on the lesser curvature. | By, Public Domain,


    • Spleen, diaphragm, omentum, transverse colon, liver, lung
    • Kruckenberg tumour: Ovary
    • Blummer shelf tumour: Pouch of Douglas
    • Sister Mary Joseph node: Periumbilical region
      • Also found in:
        • Gastric cancer
        • Colon cancer
        • Pancreatic cancer
        • Gynaecological cancer
    • Virchow node: Left supraclavicular lymph node
    • Irish node: Left anterior axillary lymph node


  • Epigastric pain
  • Anaemia
  • Fatigue
  • Early satiety
  • Anorexia
  • Dysphagia
  • Vomiting

Dermatological signs:

  • Lesser Trelat sign: Multiple seborrhoeic keratosis
  • Tripe palms: Hyperkeratotic palms
  • Sister Mary Joseph nodules: Periumbilical metastasis
  • Irish nodules: Left axillary LN
  • Troisier sign: Clinical finding of a hard and enlarged left supraclavicular node (Virchow node)



  • Contrast radiography and endoscopy
  • Serum pepsinogen levels
  • H. pylori serology
    • ELISA or HelicoTest
    • Benchmark urea breath test (UBT)
  • Serum trefoil factor 3
Possible non-invasive diagnostic biomarkers for early-stage gastric cancer. Genetic and epigenetic alterations, microRNAs, long non-coding RNAs and circular RNA, circulating tumor cells and tumor DNA represent promising candidates for the development of new non-invasive methods in early-diagnosis of gastric cancer. GC: Gastric cancer; miRNAs: MicroRNAs; lncRNAs: Long non-coding RNAs; circRNA: circular RNA; CTCs: Circulating tumor cells; cfDNAs: Cell-free circulating DNA. | Necula, L., Matei, L., Dragu, D., Neagu, A. I., Mambet, C., Nedeianu, S., … Chivu-Economescu, M. (2019). Recent advances in gastric cancer early diagnosis. World Journal of Gastroenterology, 25(17), 2029–2044.

EGD + biopsy:

Best initial diagnostic for any elderly patient with dysphagia


  • Upper GI seies “Barium roentgenogram”
    • Series of radiographs used to examine the gastrointestinal tract for abnormalities
  • Endoscopic ultrasound (EUS)
  • CT scan
Sequence of 123-iodide total-body scintiscans of a woman after intravenous injection of 123-iodide (half-life: 13 hours); (from left) respectively at 30 minutes, and at 6, 20 and 48 hours. High and rapid concentration of radio-iodide (in white) in extra-thyroidal organs is evident in gastric mucosa of the stomach, epidermis, salivary glands, periencephalic and cerebro-spinal fluid, choroid plexus and oral mucosa. In gastric mucosa 131-iodide (half-life: 8 days) persists in scintiscans for more than 72 hours. In the thyroid, iodide-concentration is more progressive, as in a reservoir [from 1% (after 30 minutes) to 5.8 % (after 48 hours) of the total injected dose]. High iodide-concentration by the mammary gland is evident only in pregnancy and lactation. High excretion of radio-iodide is observed in the urine. | By Venturi Sebastiano – Own work, CC BY-SA 3.0,


  • Eradication of H pylori infection

Dietary changes:

  • Increase fresh fruits & vegetables
  • Reduce salt consumption

Surgical management:

  • No metastasis: Subtotal or total gastrectomy
  • Metastasis: Palliative surgery


  • 5-FU or leucovorin


Early gastric cancer:

  • 5-year survival rate: 90%

Late gastric cancer:

  • Average 5-year survival rate: <20%
    • Mainly because of late diagnosis, because the early stages are clinically silent
Chen, YC., Fang, WL., Wang, RF. et al. Clinicopathological Variation of Lauren Classification in Gastric Cancer. Pathol. Oncol. Res. 22, 197–202 (2016).

Gastric adenocarcinoma. (2017). Nature Reviews Disease Primers, 3(1), 17037.

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