Gastric Cancer

Gastric adenocarcinoma is the prototypical "silent" GI malignancy — often presenting late with metastatic stigmata. For NEET PG, the high-yield clusters are: risk factors (H. pylori, nitrosamines, pernicious anaemia), the Lauren and Borrmann classifications, the constellation of metastatic eponymous signs, and the surgical decision-making around subtotal vs total gastrectomy and D1 vs D2 lymphadenectomy.

Definition & epidemiology

Gastric cancer is a malignant neoplasm arising from the stomach wall; >90–95% are adenocarcinomas arising from the glandular epithelium. The remainder include lymphoma (MALT), gastrointestinal stromal tumour (GIST), carcinoid, and rare squamous/adenosquamous lesions.

• Globally a leading cancer in East Asia (Japan, Korea, China); Japan has the highest incidence and runs national endoscopic screening, which is why early gastric cancer is far more commonly detected there.
• In India the incidence is moderate but higher in the South (Chennai) and North-East (Mizoram, Nagaland — smoked/salted foods).
• Male:female ≈ 2:1; peak incidence in the 6th–7th decade.
• There has been a global shift: distal (antral/body) cancers are falling (linked to falling H. pylori prevalence and refrigeration), while proximal/cardia and gastro-oesophageal junction (GEJ) cancers are rising (linked to obesity and reflux/Barrett's).

High-yield: H. pylori is a Group 1 (definite) carcinogen (IARC/WHO) and the single most important risk factor for distal/non-cardia gastric adenocarcinoma and gastric MALT lymphoma. It is not associated with proximal/cardia cancer.

Etiology & risk factors

Category	Specific factors
Infection	Helicobacter pylori (esp. CagA+ strains); EBV-associated gastric carcinoma
Dietary	Nitrosamines / N-nitroso compounds, salted/smoked/pickled foods, high salt; low intake of fresh fruit & vegetables (protective: vitamin C, refrigeration)
Premalignant conditions	Chronic atrophic gastritis, intestinal metaplasia, pernicious anaemia (≈ 3× risk), gastric adenomatous polyps, Ménétrier's disease, prior partial gastrectomy (gastric stump cancer, latency 15–20 yrs)
Lifestyle	Smoking, alcohol, obesity (cardia)
Genetic / familial	Hereditary diffuse gastric cancer (HDGC) — CDH1 (E-cadherin) germline mutation; HNPCC/Lynch, FAP, Li-Fraumeni, Peutz-Jeghers; blood group A

High-yield: Germline CDH1 (E-cadherin) mutation → hereditary diffuse gastric cancer (signet-ring/diffuse type) and lobular breast cancer. Prophylactic total gastrectomy is offered to carriers.

High-yield: Correa's cascade (the classic intestinal-type sequence): Normal mucosa → chronic gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → carcinoma, driven by H. pylori and nitrosamines.

Pathology & classification

Lauren classification (most tested)

Feature	Intestinal type	Diffuse type
Architecture	Gland-forming, cohesive cells	Poorly cohesive, signet-ring cells
Spread	Expanding/exophytic	Infiltrative
Site	Distal stomach, antrum	Whole stomach / cardia
Background	H. pylori, atrophic gastritis, intestinal metaplasia (Correa cascade)	CDH1 loss; younger patients
Epidemiology	Endemic, older, male, environmental	Sporadic, younger, F≈M
Prognosis	Better	Worse
Classic lesion	Polypoid/ulcerative mass	Linitis plastica ("leather-bottle stomach")

High-yield: Linitis plastica = diffuse infiltration giving a rigid, non-distensible "leather-bottle" stomach; it is a diffuse-type (signet-ring) cancer with a poor prognosis. Signet-ring cell = nucleus pushed to periphery by intracytoplasmic mucin.

Borrmann classification (macroscopic, for advanced gastric cancer)

1. Type I — Polypoid / fungating
2. Type II — Ulcerated with sharply demarcated raised margins
3. Type III — Ulcerated with infiltration of the wall (most common)
4. Type IV — Diffusely infiltrating (linitis plastica)

Early gastric cancer (EGC)

Defined as carcinoma limited to mucosa and/or submucosa, irrespective of lymph node status (i.e. T1, any N). The Japanese (Paris) endoscopic classification: Type I (protruded), Type II a/b/c (superficial elevated/flat/depressed), Type III (excavated). EGC carries an excellent prognosis (5-yr survival >90%) and is the rationale for Japanese screening.

WHO / histologic grade

Tubular, papillary, mucinous, poorly cohesive (incl. signet-ring) types; graded G1–G3.

Spread & metastasis (eponyms — extremely high-yield)

Sign / node	Description
Virchow's node (Troisier's sign)	Enlarged left supraclavicular node (via thoracic duct)
Sister Mary Joseph nodule	Metastatic periumbilical nodule
Krukenberg tumour	Transcoelomic spread to ovaries (bilateral, signet-ring cells)
Blumer's shelf	Drop metastasis to rectovesical / rectouterine pouch, palpable on PR
Irish node	Left axillary node
Acanthosis nigricans / Leser-Trélat sign	Paraneoplastic dermatoses (sudden eruptive seborrhoeic keratoses)

Routes: direct extension; lymphatic (regional perigastric → coeliac nodes); haematogenous (liver most common, then lung, bone); transcoelomic (peritoneal carcinomatosis, Krukenberg, Blumer's shelf).

Mnemonic — metastatic nodes: "Virchow Is Seriously Killer Bad" → Virchow, Irish, Sister Mary Joseph, Krukenberg, Blumer.

Clinical features

• Early disease is usually asymptomatic or has vague dyspepsia.
• Advanced: weight loss, persistent epigastric pain, early satiety, anorexia, iron-deficiency anaemia (occult bleeding), haematemesis/melaena.
• Site-specific: proximal/cardia → dysphagia; antral/pyloric → gastric outlet obstruction (vomiting, succussion splash).
• Signs of advanced disease: palpable epigastric mass, hepatomegaly, Virchow's node, ascites, Sister Mary Joseph nodule.
• Paraneoplastic: acanthosis nigricans, Leser-Trélat sign, migratory thrombophlebitis (Trousseau's syndrome), microangiopathic haemolytic anaemia, membranous nephropathy.

High-yield (alarm/red-flag dyspepsia): New-onset dyspepsia >55 years OR dyspepsia with Anaemia, Loss of weight, Anorexia, Recent persistent symptoms, Melaena/haematemesis, Swallowing difficulty (mnemonic ALARMS) → mandates urgent upper GI endoscopy.

Diagnosis & investigations

Investigation of choice for diagnosis → Upper GI endoscopy (OGD) with multiple biopsies.

• Take ≥6–8 biopsies from the ulcer edge (a single biopsy may miss diffuse type). Brush cytology adds yield. Every gastric ulcer needs biopsy, and benign-looking ulcers need repeat endoscopy to confirm healing.
• Endoscopic ultrasound (EUS) → best for assessing depth of invasion (T stage) and perigastric nodes; guides whether endoscopic resection is feasible.
• Staging investigation of choice → CECT chest/abdomen/pelvis for M staging.
• Staging (diagnostic) laparoscopy with peritoneal washings/cytology — done before major resection to detect occult peritoneal metastases (a frequent cause of CT-occult M1 disease).
• PET-CT — useful in intestinal type; less sensitive in diffuse/signet-ring & mucinous tumours (low FDG avidity).
• Tumour markers (CEA, CA 19-9, CA 72-4) — for follow-up, not diagnosis.

Staging (AJCC TNM, simplified)

• T: T1 mucosa/submucosa (T1a/T1b) → T2 muscularis propria → T3 subserosa → T4 serosa/adjacent organs.
• N: by number of positive nodes (N1 = 1–2, N2 = 3–6, N3 = ≥7).
• M0/M1. Positive peritoneal cytology = M1.

High-yield: EUS is the best test for T and N local staging; CECT + diagnostic laparoscopy detect distant/peritoneal M disease.

Management

Approach (resectable, non-metastatic): Staging (EUS + CECT + laparoscopy) → Multidisciplinary team → Perioperative (neoadjuvant) chemotherapy → Surgical resection with adequate margins + D2 lymphadenectomy → Adjuvant chemo/chemoradiation → Surveillance.

Surgical principles

• Goal: R0 resection (microscopically clear margins) — aim for a proximal margin of ≥5 cm (≥6–8 cm in diffuse type) of grossly normal stomach.

Tumour location	Recommended resection
Distal third (antrum/body)	Subtotal (distal) gastrectomy — equivalent survival to total, lower morbidity
Proximal third / cardia / diffuse / linitis plastica	Total gastrectomy (often with Roux-en-Y oesophagojejunostomy)
Early gastric cancer (T1a, well-differentiated, no ulcer, ≤2 cm, no LVI)	Endoscopic mucosal resection (EMR) / ESD

High-yield: For distal gastric cancer, subtotal gastrectomy is preferred over total gastrectomy — it gives equivalent oncological survival with lower morbidity/mortality and better nutrition, provided an adequate proximal margin is achievable.

D1 vs D2 lymphadenectomy

• D1 = removal of perigastric nodes (stations 1–6).
• D2 = D1 + nodes along the named coeliac axis vessels (left gastric, common hepatic, splenic artery, coeliac — stations 7–11).
• D2 is the standard of care. Modern spleen- and pancreas-preserving D2 dissection improves locoregional control without the excess mortality seen in older Western trials (which routinely removed spleen/pancreatic tail). A minimum of ≥15 nodes should be examined for adequate staging.

High-yield: Routine splenectomy/distal pancreatectomy is NOT done during D2 dissection unless directly involved — it increased morbidity/mortality in the early Dutch & MRC trials without survival benefit.

Reconstruction

• Subtotal gastrectomy → Billroth I (gastroduodenostomy) or Billroth II / Roux-en-Y gastrojejunostomy.
• Total gastrectomy → Roux-en-Y oesophagojejunostomy (preferred to limit bile reflux).

Chemotherapy / chemoradiation (drug regimens)

• Perioperative (neoadjuvant + adjuvant) chemotherapy is the Western standard: the FLOT regimen (5-FU, Leucovorin, Oxaliplatin, Docetaxel) has superseded the older ECF/MAGIC (Epirubicin, Cisplatin, 5-FU) regimen.
• East Asian practice favours surgery + adjuvant chemotherapy (e.g. S-1, or capecitabine + oxaliplatin — CLASSIC trial).
• Adjuvant chemoradiation (5-FU based — INT-0116/Macdonald) for patients who had inadequate (<D2) nodal dissection.

Metastatic / palliative & targeted therapy

• Palliative chemotherapy (platinum + fluoropyrimidine) ± targeted agents.
• HER2-positive tumours → add trastuzumab (ToGA trial).
• Anti-angiogenic ramucirumab (anti-VEGFR2), and immunotherapy (nivolumab/pembrolizumab — esp. MSI-high, PD-L1+, EBV+ tumours).
• Palliative measures: stenting/bypass for obstruction, endoscopic haemostasis, nutritional support.

High-yield: Test HER2 status in all advanced/metastatic gastric adenocarcinoma → if positive, add trastuzumab to chemotherapy.

Complications

• Of the disease: gastric outlet obstruction, dysphagia, perforation, bleeding/anaemia, peritoneal carcinomatosis with malignant ascites, malnutrition/cachexia.
• Post-gastrectomy syndromes (high-yield):
  • Dumping syndrome — early (osmotic, 15–30 min: cramps, diarrhoea, vasomotor) and late (reactive hypoglycaemia, 1–3 h). Management: small frequent meals, low simple-carbohydrate, separate fluids from solids; octreotide if refractory.
  • Afferent loop syndrome / blind loop (after Billroth II).
  • Bile (alkaline) reflux gastritis — managed by conversion to Roux-en-Y.
  • Vitamin B12 deficiency (loss of intrinsic factor; needs lifelong parenteral B12 after total gastrectomy), iron & folate deficiency, osteoporosis/osteomalacia.
  • Anastomotic leak, duodenal stump blowout.

Prognosis

• Overall poor because of late presentation — depends mainly on stage (depth of invasion + nodal status) and completeness of resection (R0).
• Early gastric cancer 5-yr survival >90%; advanced node-positive disease <20–30%.
• Diffuse/signet-ring (linitis plastica) and proximal tumours fare worse than intestinal/distal.

Key differentials

• Benign gastric ulcer (must biopsy to exclude malignancy).
• Gastric lymphoma (MALT) — H. pylori-driven; low-grade MALT may regress with H. pylori eradication alone (key MCQ point).
• GIST — submucosal, c-KIT (CD117)/DOG1 positive, treated with imatinib; spreads haematogenously, rarely to nodes.
• Gastric carcinoid (neuroendocrine tumour), metastasis to stomach (e.g. melanoma, breast lobular), Ménétrier's disease, hypertrophic gastritis.

Feature	Adenocarcinoma	MALT lymphoma	GIST
Cell of origin	Glandular epithelium	B lymphocytes (MALT)	Interstitial cells of Cajal
Key association	H. pylori, nitrosamines	H. pylori	c-KIT/PDGFRA mutation
Marker	CEA, CK	CD20	CD117 (c-KIT), DOG1
Spread	Lymphatic/transcoelomic	Nodal	Haematogenous (liver)
First-line treatment	Surgery + chemo	H. pylori eradication (low-grade)	Imatinib + surgery

Recently asked / exam angle

• Lauren classification intestinal vs diffuse — link diffuse type to signet-ring cells, linitis plastica, CDH1/E-cadherin, younger patients, worse prognosis.
• Match the eponymous metastases: Virchow (left supraclavicular), Sister Mary Joseph (umbilical), Krukenberg (ovary), Blumer's shelf (rectouterine pouch), Irish (axillary).
• "Most common site of distant (haematogenous) metastasis" → liver.
• Investigation matching: EUS = best for T staging; OGD + biopsy = diagnosis of choice; staging laparoscopy detects peritoneal disease.
• Subtotal vs total gastrectomy based on tumour location; D2 over D1; no routine splenectomy.
• Definition of early gastric cancer (limited to mucosa/submucosa irrespective of node status).
• HER2 → trastuzumab (ToGA); perioperative FLOT; low-grade MALT regresses with H. pylori eradication.
• H. pylori as a Group 1 carcinogen, not linked to cardia cancer.

Rapid revision

1. Most common gastric malignancy = adenocarcinoma; H. pylori is the chief risk factor for distal cancer and a Group 1 carcinogen.
2. Correa cascade: gastritis → atrophy → intestinal metaplasia → dysplasia → intestinal-type carcinoma.
3. Lauren: intestinal (better, distal, Correa) vs diffuse (worse, signet-ring, CDH1, linitis plastica).
4. Borrmann IV = linitis plastica = leather-bottle stomach.
5. Early gastric cancer = confined to mucosa ± submucosa, any node status; 5-yr survival >90%.
6. Eponyms: Virchow (L supraclavicular), Sister Mary Joseph (umbilicus), Krukenberg (ovary), Blumer's shelf (pelvic pouch), Irish (L axilla), Troisier's sign.
7. Diagnosis of choice = OGD + multiple biopsies; EUS = best T-staging; CECT + laparoscopy for M staging.
8. CDH1 mutation → hereditary diffuse gastric cancer → consider prophylactic total gastrectomy.
9. Distal cancer → subtotal gastrectomy (≥5 cm margin); proximal/diffuse → total gastrectomy with Roux-en-Y.
10. D2 lymphadenectomy is standard; spleen/pancreas preserved; examine ≥15 nodes.
11. Perioperative chemo = FLOT; HER2+ → add trastuzumab; MALT (low-grade) → eradicate H. pylori.
12. After total gastrectomy → lifelong parenteral vitamin B12; watch for dumping syndrome.