Gastric Cancer
Adenocarcinoma of the stomach; H. pylori-driven; often diagnosed late with poor prognosis.
Also known as: gastric cancer, stomach cancer, gastric adenocarcinoma
Overview
Malignant neoplasm of the stomach, predominantly adenocarcinoma (>90%). Lauren classification: intestinal type (well-differentiated, glandular, associated with H. pylori/atrophic gastritis) and diffuse type (poorly cohesive, signet-ring cells, linitis plastica, hereditary CDH1 mutation in some).
Epidemiology
~27,000 new cases and ~11,000 deaths annually in the US. Worldwide, 5th most common cancer; high incidence in East Asia, Eastern Europe, and Latin America. 5-year survival ~33% (US); >60% in countries with screening (Japan, South Korea).
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Risk factors
- H. pylori infection (Group 1 carcinogen) — strongest risk factor for non-cardia gastric cancer
- Chronic atrophic gastritis with intestinal metaplasia
- Pernicious anemia / autoimmune metaplastic atrophic gastritis
- Diet: high salt, smoked/cured foods, nitrosamines, low fruits/vegetables
- Smoking, alcohol
- Obesity (cardia cancer)
- Family history; CDH1 mutation (hereditary diffuse gastric cancer)
- Lynch syndrome, FAP, Peutz-Jeghers
- EBV infection (~10% of cases)
- Previous gastric surgery (post-gastrectomy stump cancer)
- Ménétrier disease, gastric adenomatous polyps
Pathophysiology
Intestinal-type follows the Correa cascade: H. pylori-induced chronic gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → carcinoma. Diffuse type arises de novo, often associated with CDH1 (E-cadherin) loss producing poorly cohesive signet-ring cells infiltrating the stomach wall (linitis plastica — leather bottle stomach).
Clinical presentation
Symptoms
- Often asymptomatic until advanced
- Epigastric pain or dyspepsia
- Early satiety, postprandial fullness
- Anorexia, weight loss
- Nausea, vomiting (gastric outlet obstruction)
- Hematemesis, melena, occult GI bleeding (iron-deficiency anemia)
- Dysphagia (cardia tumors)
Signs / physical exam
- Palpable epigastric mass (late)
- Virchow node (left supraclavicular)
- Sister Mary Joseph nodule (periumbilical)
- Blumer shelf (rectal exam — pelvic peritoneal spread)
- Krukenberg tumor (ovarian metastasis, signet-ring cells)
- Irish node (left axillary)
- Acanthosis nigricans, Leser-Trélat sign (paraneoplastic)
- Hepatomegaly if liver metastases
Classic findings
Older adult with new dyspepsia, weight loss, and iron-deficiency anemia.
Differential diagnosis
- Peptic ulcer disease — Benign ulcers can mimic; biopsy ALL gastric ulcers; repeat EGD to confirm healing
- Gastric lymphoma (MALT or DLBCL) — H. pylori association; biopsy with immunohistochemistry; MALT may regress with H. pylori treatment
- GIST (gastrointestinal stromal tumor) — Submucosal mass; KIT/PDGFRA+; biopsy via EUS; treat with imatinib
- Functional dyspepsia — Normal EGD; same symptoms; diagnosis of exclusion
- Gastroparesis — Early satiety, vomiting undigested food; gastric emptying study
- Pancreatic cancer (with gastric outlet obstruction) — Painless jaundice, weight loss; pancreatic mass on CT
Diagnostic workup
Diagnostic criteria
Histologic confirmation on biopsy. HER2, MMR/MSI, PD-L1 testing on all advanced/metastatic cases to guide systemic therapy. Staging by AJCC 8th edition TNM.
Labs
- CBC (microcytic anemia)
- BMP, LFTs, albumin
- H. pylori testing
- CEA, CA 19-9, CA 72-4 — not diagnostic; may aid in surveillance
Imaging
- Upper endoscopy with biopsy — diagnostic; multiple biopsies of any ulcer or mass
- Endoscopic ultrasound (EUS) — accurate T and N staging; allows FNA of lymph nodes
- CT chest/abdomen/pelvis with contrast — staging, metastases
- PET-CT — selected cases; useful for detecting distant disease
- Diagnostic laparoscopy with peritoneal washings — recommended for T3/T4 or node-positive disease before definitive therapy (10-30% have occult peritoneal disease)
Diagnostic algorithm
| Lauren Subtype | Intestinal | Diffuse |
|---|---|---|
| Histology | Well-differentiated glands | Poorly cohesive, signet-ring cells |
| Distribution | Sporadic, regional clusters | More uniform global incidence |
| Precursor | H. pylori → atrophic gastritis → metaplasia → dysplasia | Often de novo; CDH1 mutation in hereditary |
| Age | Older | Younger |
| Sex | Male > female | Equal |
| Prognosis | Better | Worse (linitis plastica) |
| Pattern | Mass lesion | Diffuse infiltration |
Treatment
First-line
- Multidisciplinary management
- H. pylori eradication if present
- Stage-directed treatment (see by_subtype)
Early gastric cancer (T1a, well-differentiated, non-ulcerated, <2 cm)
- Endoscopic submucosal dissection (ESD) — curative in carefully selected lesions
- Surveillance EGD
Locally advanced (T2-T4 or node-positive)
- Perioperative chemotherapy with FLOT (5-FU/leucovorin/oxaliplatin/docetaxel) × 4 cycles before and after surgery — current standard (FLOT4 trial)
- Total or subtotal gastrectomy with D2 lymphadenectomy
- Adjuvant chemoradiation (capecitabine + RT) — alternative for patients who did not receive neoadjuvant therapy (MAGIC/INT-0116)
Metastatic / unresectable
- First-line palliative: fluoropyrimidine + platinum (FOLFOX, CAPOX) ± trastuzumab if HER2+ (ToGA trial)
- Immunotherapy — nivolumab or pembrolizumab added to chemotherapy depending on PD-L1 CPS and MSI status
- Second-line: ramucirumab + paclitaxel; trifluridine/tipiracil
- Palliative care, nutritional support (enteral access), management of obstruction (stent or palliative gastrojejunostomy)
Complications
- Gastric outlet obstruction
- Upper GI bleeding (acute or chronic)
- Perforation
- Malnutrition and cachexia
- Peritoneal carcinomatosis with malignant ascites
- Krukenberg tumors (bilateral ovarian metastases)
- Liver, lung, bone metastases
- Paraneoplastic: DVT (Trousseau), acanthosis nigricans, Leser-Trélat
PANCE pearls
- Biopsy ALL gastric ulcers — 4% are malignant; repeat EGD in 8-12 weeks to confirm healing.
- H. pylori eradication reduces gastric cancer risk; effect strongest when treated before atrophic gastritis or metaplasia develops.
- FLOT regimen replaced ECF as preferred perioperative chemotherapy for resectable disease (FLOT4 trial).
- HER2-positive metastatic gastric cancer benefits from trastuzumab — test all advanced cases.
- Diagnostic laparoscopy detects peritoneal disease missed by CT in 10-30% of locally advanced cases.
- Linitis plastica (diffuse infiltration) carries the worst prognosis and is typically not amenable to curative resection.
- Hereditary diffuse gastric cancer (CDH1 mutation): consider prophylactic total gastrectomy in carriers.
- Japan/Korea perform screening EGD due to high prevalence; not cost-effective in low-incidence US population.
References
- NCCN 2024 — NCCN Guidelines Version 2.2024 — Gastric Cancer
- FLOT4 — Al-Batran SE et al. Perioperative chemotherapy with FLOT versus ECF/ECX for resectable gastric or GEJ adenocarcinoma. Lancet 2019;393:1948-1957
- ToGA Trial — Bang YJ et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or GEJ cancer. Lancet 2010;376:687-697
- MAGIC Trial — Cunningham D et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. NEJM 2006;355:11-20
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