Neuroendocrine Tumours

Neuroendocrine Tumours Heterogenous group of neoplasms Share certain characteristic features Originate from neuroendocrine cells Have secretory characteristics Frequently present with hypersectretory syndromes

Neuroendocrine Tumours Pancreatic islet cells Gastroenteric tissue Respiratory epithelium Gastroenteropancreatic NETs Includes carcinoid (serotonin secreting tumour)

Presentation Asymptomatic Symptoms Present with obstructive symptoms Usually due to liver metastases Release of hormones into circulation e.g. Serotonin, tachykinin

Symptoms Intermittent abdo pain 70% Diarrhoea 50% Flushing 30% Lacrimation Rhinorrhoea Episodic palpitations Wheezing Pellagra

“Carcinoid crisis” Precipitated by Anaesthetic induction Intraoperative tumour handling Therapeutic procedures, eg embolisation Profound flushing Bronchospasm Tachycardia Widely fluctuating BP

Aetiology and Genetics Poorly understood Most are sporadic Small increased familial risk for small intestinal / colonic tumours Aim to exclude complex cancer syndromes (e.g. MEN 1, MEN 2, NF1)

Diagnosis Clinical symptoms Hormone concentrations Radiology Histology – gold standard

Hormone concentrations Plasma chromagranin A (CgA) May correlate with response and relapse Fast rising levels = poor prognosis Urine 5-HIAA (24 hrs) Certain foods affect urinary excretion and may cause false positives Pancreatic polypeptide High concentration in 80% pancreatic and 50% carcinoid Should also measure other hormones for MEN syndromes. CgA – more useful in gastric carcinoids with mets. May correlate with response and relapse- fast rising levels poor prognosis Pan polypeptide – high conc in 80% of pancreatic and 50% of carcinoid

Imaging Sensitivites (%) of various imaging modalities for locating specific neuroendocrine tumours Primary carcinoid tumour Carcinoid liver mets Ultrasound 46 83 CT 64 88 MRI 56 85 SSRS 80 90 SSRS- tumours express somatostatin receptors- use of radiolabelled som. Analogues . 90% sensitivity noted for fore/hind/mid gut tumours. Good for assessing secondaries %-sensisitvities for primaries compared to liver mets

Imaging 40-70% of patients have nodal or liver metastases at time of presentation If <2 cm diameter: low incidence of metastases

Small intestinal carcinoid: Treatment Aim should be curative Palliation in majority of cases Majority are malignant Resection of primary and mesenteric lymph nodes despite liver mets For cure / delay progression (could endanger small bowel) Can alleviate symptoms ? Prolong survival

Symptomatic Treatment Used in patient with secretory symptoms Somatostatin analogues (e.g. Octreotide) Inhibits release of many hormones Can impair some exocrine functions Hormone response in 30-70% patients Symptom control in majority Rarely tumour shrinkage

Additional medication Ondansatron nausea Cyproheptadine Cholestyramine CREON Control of diarrhoea, esp after intestinal resection

Interferon alpha Sole use or with somatostatin analogues ? Efficacy (conflicting evidence) Some evidence better in tumour with low mitotic rates Biochemical response 40-60% Symptomatic improvement 40-70% Significant tumour shrinkage 10-15%

Other options Chemotherapy Hepatic artery embolisation Role uncertain but being actively researched Response short lived (8-10 months) Hepatic artery embolisation Indicated for non resectable & multiple hormone secreting tumours Causes ischaemia of tumour cells Symptomatic response 40-80% 5 year survival 50-60%

Radionucleotide therapy Palliative option Exploits increased uptake of radiolabelled isotopes I-MIBG or octreotide Symptom control 80% Radiotherapy Carcinoid – radioresistant Relief of pain from bone mets

Prognosis No TNM classification Slow growing, but survival depends on Histological type Degree of differentiation Mitotic rate Tumour size Depth and location Lymph node/ liver metastases

Prognosis – 5 year survival