GI malignancy
Description
| Cancer | Dominant histology | Key driver |
|---|---|---|
| Oesophageal | SCC (upper/mid) vs adenocarcinoma (lower/GOJ) | SCC: alcohol, smoking, HPV. Adeno: obesity + GORD -> Barrett |
| Gastric | Adenocarcinoma - intestinal vs diffuse (signet ring) | *H. pylori, salt, smoking; CDH1* for diffuse |
| HCC | Hepatocellular | Cirrhosis of any cause; HBV without cirrhosis |
| Cholangiocarcinoma | Adenocarcinoma | PSC, liver flukes, choledochal cysts |
| Pancreatic | Ductal adenocarcinoma | Smoking, chronic pancreatitis, BRCA2, new-onset diabetes |
| Colorectal | Adenocarcinoma | Adenoma-carcinoma sequence; Lynch, FAP |
| NET / GIST | Neuroendocrine; KIT/PDGFRA | Carcinoid syndrome; GIST -> imatinib |
| Lymphoma | MALT (gastric), DLBCL | *H. pylori* (MALT); coeliac (EATL) |
- In children the commonest GI malignancy is lymphoma - crampy pain, vomiting/obstruction, bleeding, palpable mass
Epidemiology
- Colorectal cancer - the commonest GI malignancy in Australia; ~15,000 cases/yr
- In Australia, chronic HBV and HCV together cause ~70% of HCC; MASH and alcohol-related liver disease make up most of the remainder
- Oesophageal adenocarcinoma rising in the West (obesity/GORD); SCC falling
- Gastric cancer falling with H. pylori eradication and refrigeration; still dominant in East Asia
- Pancreatic cancer incidence rising; among the leading causes of cancer death despite low incidence
Aetiopathogenesis
HCC
- Cirrhosis of any aetiology is the dominant risk
- HBV causes HCC without cirrhosis (viral DNA integration -> direct oncogenesis)
- Aflatoxin (TP53 R249S), haemochromatosis, alpha-1 antitrypsin deficiency, MASH, alcohol
- Genotype C HBV, high HBV DNA, male sex, age, diabetes, obesity
Oesophageal
- SCC: alcohol, smoking (synergistic), HPV (~3x), achalasia, caustic stricture, Plummer-Vinson, hot beverages, tylosis
- Adenocarcinoma: obesity, chronic GORD -> Barrett -> dysplasia -> carcinoma
- ~10% of Barrett with dysplasia progresses to adenocarcinoma
Gastric
- **H. pylori -> chronic gastritis -> atrophy -> intestinal metaplasia -> dysplasia -> carcinoma** (Correa cascade)
- Pernicious anaemia, partial gastrectomy, EBV, smoked/salted food
- CDH1 (E-cadherin) germline -> hereditary diffuse gastric cancer -> prophylactic gastrectomy
Colorectal
- Adenoma-carcinoma sequence: APC -> KRAS -> TP53; serrated pathway (BRAF, CIMP)
- Lynch (MMR: MLH1, MSH2, MSH6, PMS2) - MSI-high, right-sided, endometrial cancer
- FAP (APC); MUTYH-associated polyposis; IBD; obesity, red/processed meat, alcohol, smoking
Diagnosis
HCC - the only solid tumour routinely diagnosed on imaging alone
- Lesion >1 cm on multiphase CT or contrast-enhanced MRI with arterial phase hyperenhancement + washout on portal venous/delayed phase = diagnostic
- No biopsy needed
- Biopsy only for indeterminate imaging (seeding risk ~1-3%)
- AFP is neither sensitive nor specific - an adjunct to ultrasound, not a diagnostic test
- Surveillance: 6-monthly liver ultrasound +/- AFP
- All cirrhosis (Child-Pugh A and B; C only if awaiting transplant)
- Non-cirrhotic chronic HBV: Asian men >40, Asian women >50, African/Black ancestry from diagnosis, active hepatitis, family history of HCC
- Non-cirrhotic chronic HCV with advanced fibrosis
- Also haemochromatosis, alpha-1 antitrypsin deficiency, stage 4 PBC
Oesophageal
- Often asymptomatic or reflux/dyspepsia early
- Locally advanced: dysphagia (solids -> liquids), weight loss, hoarseness (recurrent laryngeal nerve), hiccups (phrenic), post-prandial cough (oesophago-bronchial/tracheal fistula)
- Gastroscopy + biopsy; staging with CT, PET, and EUS for T and N stage
Gastric
- Dyspepsia, early satiety, weight loss, iron deficiency anaemia
- Virchow node (left supraclavicular), Sister Mary Joseph nodule, Krukenberg tumour, Blumer shelf, acanthosis nigricans
- Gastroscopy + multiple biopsies; linitis plastica may look normal - take deep biopsies
Pancreatic
- Painless obstructive jaundice (head), back pain, weight loss, new-onset diabetes, Courvoisier sign, migratory thrombophlebitis (Trousseau)
- Pancreatic-protocol CT; EUS + FNA; CA 19-9 for monitoring (not screening; falsely raised in cholestasis; absent in Lewis-antigen-negative people)
Colorectal
- Iron deficiency anaemia, change in bowel habit, PR bleeding, obstruction
- Colonoscopy + biopsy; CT chest/abdomen/pelvis; MRI rectum for rectal cancer; CEA baseline
- Universal MMR/MSI testing on every new colorectal cancer - Lynch screening + immunotherapy eligibility
Management
HCC - by BCLC stage
Verified against the BCLC 2026 update. The major change from older teaching: immunotherapy combinations have replaced sorafenib as first-line systemic therapy.
| Stage | Definition | Treatment |
|---|---|---|
| Very early (0) | Single lesion <2 cm, preserved function | Ablation or resection |
| Early (A) | Single <3 cm, or 2-3 lesions each <3 cm, preserved function | Resection if a surgical candidate; otherwise transplant; or ablation |
| Intermediate (B) | Multinodular, unresectable, preserved function | TACE (transarterial chemoembolisation) |
| Advanced (C) | Portal invasion or extrahepatic spread | Systemic therapy |
| Terminal (D) | Decompensated, non-transplantable | Supportive care |
Resection vs transplant for a lesion <5 cm
- Resection: immediate, ~70% 5-year survival, but recurrence or new tumour 50-60% at 5 years and ongoing decompensation risk from the cirrhosis
- Transplant: ~75% 5-year survival and treats the cirrhosis, but waiting-list time risks progression beyond criteria (Milan: single <5 cm, or up to 3 lesions each <3 cm)
- Predictors of successful resection: appropriate size/location, preserved synthetic function (albumin, bilirubin), and absence of portal hypertension
Systemic therapy (Child-Pugh A, ECOG 0-1 only)
- First line: atezolizumab + bevacizumab (IMbrave150), or durvalumab + tremelimumab (STRIDE/HIMALAYA)
- Sorafenib and lenvatinib are now second line, or used where immunotherapy/anti-VEGF is contraindicated
- Gastroscopy with banding before starting bevacizumab - antiangiogenic bleeding risk
- Toxicities: sorafenib - hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash; lenvatinib - less hand-foot, more hypertension, QT prolongation, diarrhoea, anorexia, proteinuria; immunotherapy - immune-related adverse events, and checkpoint inhibitors are avoided post-transplant (rejection)
- Only ~20-30% respond to first-line immunotherapy, and ~50% of responders progress by 6 months
Oesophageal / gastric
- Early (T1a) -> endoscopic mucosal resection / submucosal dissection
- Locally advanced -> neoadjuvant chemoradiotherapy (SCC/adeno, CROSS) or perioperative chemotherapy (FLOT) then oesophagectomy/gastrectomy
- Metastatic -> palliative chemotherapy; HER2 testing -> trastuzumab; PD-L1 -> checkpoint inhibitor; stent or radiotherapy for dysphagia
- *Gastric MALT lymphoma -> eradicate H. pylori*** (regresses in ~70-80% if t(11;18) negative)
Pancreatic
- Only ~20% resectable -> Whipple / distal pancreatectomy + adjuvant chemotherapy (mFOLFIRINOX)
- Borderline resectable -> neoadjuvant chemotherapy
- Metastatic -> FOLFIRINOX or gemcitabine/nab-paclitaxel; germline BRCA -> platinum, then olaparib maintenance
- Palliative: biliary stent, coeliac plexus block, pancreatic enzyme replacement
Colorectal
- Colon: resection + adjuvant chemotherapy for stage III (and high-risk II)
- Rectal: neoadjuvant chemoradiotherapy / total neoadjuvant therapy; watch-and-wait for complete clinical response
- Metastatic: resect liver/lung oligometastases; chemotherapy + biologics by RAS/BRAF status; dMMR/MSI-high -> checkpoint inhibitor
Associations
- PSC -> cholangiocarcinoma and gallbladder cancer (and colorectal cancer with IBD)
- Coeliac disease -> enteropathy-associated T-cell lymphoma, small bowel adenocarcinoma
- **H. pylori -> gastric adenocarcinoma and gastric MALT lymphoma**
- Barrett oesophagus -> adenocarcinoma
- Achalasia -> oesophageal SCC (long latency)
- Chronic pancreatitis, hereditary pancreatitis (PRSS1) -> pancreatic cancer
- Lynch syndrome - colorectal, endometrial, gastric, small bowel, urothelial, ovarian
- FAP - colorectal, duodenal/ampullary, desmoid, thyroid
- Peutz-Jeghers (STK11) - GI, breast, pancreas; mucocutaneous pigmentation
- Paraneoplastic: acanthosis nigricans, dermatomyositis, Trousseau syndrome
Natural history & complications
Prognosis
- Pancreatic - worst; 5-year survival ~10%
- Oesophageal ~20-25%; gastric ~30-35% in the West
- HCC depends entirely on stage and liver function - many patients die of the cirrhosis, not the tumour
- Colorectal - best, ~70% overall; >90% for stage I
Key numbers
- HCC after resection: recurrence 50-60% at 5 years (a field defect, not just residual tumour)
- Barrett with dysplasia: ~10% progress to adenocarcinoma
- HCC in cirrhosis: ~2-4% per year (1-2%/yr in MASH or autoimmune cirrhosis)
Follow-up
- CRC: colonoscopy at 1 year then by findings; CEA 3-monthly for 3 years; CT surveillance
- HCC: imaging 3-monthly initially after curative therapy
- Post-oesophagectomy/gastrectomy: B12, iron, calcium, dumping syndrome, nutritional support
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