Colorectal neuroendocrine tumours

Overview

•Arise from enterochromaffin (Kulchitsky) cells of the gut - formerly called 'carcinoid tumours'

•Rectum is the most common colorectal site; many small rectal NETs found incidentally on colonoscopy

•Carcinoid syndrome = hepatic (or distant) metastases until proven otherwise - serotonin bypasses hepatic first-pass metabolism

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Right-sided cardiac disease (tricuspid regurgitation, pulmonary stenosis) occurs because the pulmonary bed inactivates serotonin before it reaches the left heart - mitral/aortic involvement is rare.

Presentation

•Asymptomatic - most small (<1 cm) rectal NETs found incidentally

•Local symptoms - rectal bleeding, altered bowel habit, abdominal pain

•Carcinoid syndrome (hepatic metastases): episodic flushing, watery diarrhoea, bronchospasm, right-sided valvular disease

•Pellagra - dermatitis, diarrhoea, dementia from niacin deficiency (tryptophan diverted to serotonin synthesis)

Investigations

🥇 First-line

•Chromogranin A (CgA) - most sensitive serum marker; elevated in >80%; note PPIs cause false elevation

•24-hour urinary 5-HIAA - urinary serotonin metabolite; use when carcinoid syndrome suspected

•Colonoscopy with biopsy - histological diagnosis + Ki-67 grading + immunohistochemistry (synaptophysin, CgA)

•CT chest/abdomen/pelvis - staging; MRI liver more sensitive for hepatic metastases

•Echocardiogram - all patients with suspected carcinoid syndrome to assess tricuspid/pulmonary valve disease

🏆 Gold standard

•Ga-68 DOTATATE PET-CT (superseded Octreoscan) - detects occult metastases; guides eligibility for PRRT

Management

•Localised rectal NETs - size-based:

•<1 cm, submucosal: endoscopic resection (EMR or ESD) - curative, <2% metastatic risk

•1-2 cm or muscularis propria invasion: surgical resection (transanal or low anterior resection); metastatic risk 10-15%

•>2 cm: radical resection with lymphadenectomy; metastatic risk >60%; MDT decision required

•Symptom control (carcinoid syndrome): octreotide 100-200 micrograms SC three times daily (short-acting) or lanreotide 120 mg deep SC every 28 days - suppresses hormone secretion and antiproliferative (CLARINET/PROMID trials show PFS benefit in G1/G2)

•Loperamide - symptomatic diarrhoea control alongside somatostatin analogues

•Progressive/metastatic somatostatin receptor-positive disease: PRRT with lutetium-177 DOTATATE (Lutathera) - NICE-approved; targeted radiotherapy to tumour cells

•Progressive G1/G2 not amenable to PRRT: everolimus (mTOR inhibitor) or sunitinib (tyrosine kinase inhibitor)

•Poorly differentiated NEC (G3): etoposide + cisplatin or carboplatin - analogous to small-cell lung cancer treatment

•Liver-dominant metastases: hepatic-directed therapy (transarterial embolisation, radiofrequency ablation)

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Carcinoid crisis - life-threatening perioperative emergency (massive vasoactive mediator release during tumour manipulation). Features: severe flushing, profound hypo/hypertension, bronchospasm, tachyarrhythmia. Prevent with octreotide infusion perioperatively (100-500 micrograms IV bolus then infusion); treat acute crisis with IV octreotide immediately.

Prognosis

•Small well-differentiated rectal NETs (<1 cm, G1): 5-year survival ~95-100% after endoscopic resection

•Hepatic metastases: 5-year survival ~20-40%

•Poorly differentiated NEC: median survival <12 months even with chemotherapy

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PPIs cause false elevation of chromogranin A - always check medication history before interpreting CgA results.