Gastrointestinal · PANCE / PANRE

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).

🔒 Free preview limit reached

Keep reading — start your free trial

You've read your 2 free diagnosis previews. Create your free account to unlock the full Gastric Cancer outline — plus all 514 diagnoses, 3,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.

Free to start · No credit card · Cancel anytime

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 SubtypeIntestinalDiffuse
HistologyWell-differentiated glandsPoorly cohesive, signet-ring cells
DistributionSporadic, regional clustersMore uniform global incidence
PrecursorH. pylori → atrophic gastritis → metaplasia → dysplasiaOften de novo; CDH1 mutation in hereditary
AgeOlderYounger
SexMale > femaleEqual
PrognosisBetterWorse (linitis plastica)
PatternMass lesionDiffuse infiltration
Lauren classification of gastric adenocarcinoma — intestinal vs diffuse type.

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

Practice Gastrointestinal questions on FirstPassPA

Turn this outline into retention. 3,500+ board-style questions with an AI tutor that explains every answer — free to start, no card required.

Start studying free → Browse all 514 diagnoses

Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants.