Gastric cancer

Overview

•H. pylori - WHO Group 1 carcinogen; most important modifiable cause; follows Correa cascade (chronic gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → adenocarcinoma)

•Pernicious anaemia - 2-3 fold increased risk; B12 replacement corrects anaemia but does NOT reverse atrophic gastritis; persistent achlorhydria and parietal cell loss sustains malignant transformation risk

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Pernicious anaemia = low B12 + macrocytic anaemia + angular cheilitis. Even with adequate B12 injections, the underlying atrophic gastritis persists - the gastric cancer risk remains.

Presentation

•Dyspepsia - persistent, refractory to PPIs; PPI failure is a red flag

•Unintentional weight loss - red flag

•Anorexia / early satiety - especially characteristic of linitis plastica

•Nausea and vomiting - vomiting of undigested food suggests gastric outlet obstruction

•Haematemesis / melaena / iron deficiency anaemia - tumour ulceration

•Acanthosis nigricans - velvety, hyperpigmented thickening of skin folds (axilla, groin, neck); paraneoplastic; 90% of malignant cases are gastrointestinal adenocarcinoma

•Virchow's node - enlarged left supraclavicular node (Troisier's sign); lymphatic spread via thoracic duct

•Krukenberg tumour - ovarian metastasis via transcoelomic spread; signet ring cells; diffuse-type gastric cancer

•Sister Mary Joseph nodule - periumbilical nodule; peritoneal metastasis

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Velvety hyperpigmented skin in the axilla or groin + weight loss + epigastric symptoms = gastric adenocarcinoma until proven otherwise. Gastric squamous cell carcinoma is associated with acrokeratosis paraneoplastica, NOT acanthosis nigricans.

Investigations

🏆 Gold standard

•OGD with biopsy - histology (adenocarcinoma, signet ring cells), CLO test (H. pylori), HER2/neu expression

•First-line staging: CT chest-abdomen-pelvis - TNM staging

•Staging laparoscopy - mandatory before curative surgery; detects peritoneal metastases not visible on CT

•NICE NG12 2WW referral: age ≥55 with weight loss + upper abdominal pain/reflux/dyspepsia; any age with dysphagia or upper abdominal mass

Management

•First-line (resectable disease): perioperative FLOT (docetaxel, oxaliplatin, leucovorin, fluorouracil) - 4 cycles neoadjuvant + surgery + 4 cycles adjuvant

•Surgery: total gastrectomy (proximal tumours) or subtotal/distal gastrectomy (antral/distal tumours)

•Palliative chemotherapy: cisplatin + fluorouracil ± trastuzumab if HER2-positive - for metastatic disease

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All metastatic gastric adenocarcinoma should have HER2/neu tested at biopsy. HER2-positive (~15-20%) = add trastuzumab to palliative chemotherapy.

Complications

•Vitamin B12 deficiency post-gastrectomy - removal of parietal cells eliminates intrinsic factor; lifelong IM B12 replacement required after total gastrectomy

•Dumping syndrome - early (10-30 min): vasomotor symptoms from rapid osmotic fluid shift; late (1-3 h): reactive hypoglycaemia from insulin surge

•Gastric outlet obstruction - antral tumour; projectile vomiting of undigested food, succussion splash