Neuroendocrine TumoursNeuroendocrine Tumours

Neuroendocrine TumoursNeuroendocrine Tumours

Heterogenous group of neoplasmsHeterogenous group of neoplasms Share certain characteristic featuresShare certain characteristic features

– Originate from neuroendocrine cellsOriginate from neuroendocrine cells– Have secretory characteristicsHave secretory characteristics– Frequently present with hypersectretory Frequently present with hypersectretory

syndromessyndromes

Neuroendocrine TumoursNeuroendocrine Tumours

Pancreatic islet cells Pancreatic islet cells Gastroenteric tissueGastroenteric tissue Respiratory epitheliumRespiratory epithelium

Gastroenteropancreatic NETsGastroenteropancreatic NETs Includes carcinoid (serotonin Includes carcinoid (serotonin

secreting tumour)secreting tumour)

PresentationPresentation

AsymptomaticAsymptomatic– Present with obstructive symptomsPresent with obstructive symptoms

SymptomsSymptoms– Usually due to liver metastases Usually due to liver metastases – Release of hormones into circulation e.g. Release of hormones into circulation e.g.

Serotonin, tachykininSerotonin, tachykinin

SymptomsSymptoms

Intermittent abdo pain Intermittent abdo pain 70%70% DiarrhoeaDiarrhoea 50%50% FlushingFlushing 30%30% LacrimationLacrimation RhinorrhoeaRhinorrhoea Episodic palpitationsEpisodic palpitations Wheezing Wheezing PellagraPellagra

““Carcinoid crisis”Carcinoid crisis”

Precipitated byPrecipitated by Anaesthetic inductionAnaesthetic induction

Intraoperative tumour handlingIntraoperative tumour handlingTherapeutic procedures, eg embolisationTherapeutic procedures, eg embolisation

Profound flushingProfound flushingBronchospasmBronchospasmTachycardiaTachycardiaWidely fluctuating BPWidely fluctuating BP

Aetiology and GeneticsAetiology and Genetics

Poorly understoodPoorly understood Most are sporadicMost are sporadic Small increased familial risk for small Small increased familial risk for small

intestinal / colonic tumoursintestinal / colonic tumours Aim to exclude complex cancer Aim to exclude complex cancer

syndromes (e.g. MEN 1, MEN 2, NF1)syndromes (e.g. MEN 1, MEN 2, NF1)

DiagnosisDiagnosis

Clinical symptomsClinical symptoms Hormone concentrationsHormone concentrations RadiologyRadiology HistologyHistology – gold standard – gold standard

Hormone concentrationsHormone concentrations Plasma chromagranin A (CgA)Plasma chromagranin A (CgA)

– May correlate with response and relapseMay correlate with response and relapse– Fast rising levels = poor prognosisFast rising levels = poor prognosis

Urine 5-HIAA (24 hrs)Urine 5-HIAA (24 hrs)– Certain foods affect urinary excretion and may Certain foods affect urinary excretion and may

cause false positivescause false positives Pancreatic polypeptidePancreatic polypeptide

– High concentration in 80% pancreatic and 50% High concentration in 80% pancreatic and 50% carcinoidcarcinoid

Should also measure other hormones for Should also measure other hormones for MEN syndromes. MEN syndromes.

ImagingImaging Sensitivites (%) of various imaging modalities for Sensitivites (%) of various imaging modalities for

locating specific neuroendocrine tumourslocating specific neuroendocrine tumours

Primary carcinoid Primary carcinoid tumourtumour

Carcinoid liver Carcinoid liver metsmets

UltrasoundUltrasound 4646 8383

CTCT 6464 8888

MRIMRI 5656 8585

SSRSSSRS 8080 9090

ImagingImaging

40-70% 40-70% of patients have nodal or of patients have nodal or liver metastases at time of liver metastases at time of presentationpresentation

If <2 cm diameter: low incidence of If <2 cm diameter: low incidence of metastasesmetastases

Small intestinal carcinoid: Small intestinal carcinoid: TreatmentTreatment

Aim should be curativeAim should be curative Palliation in majority of casesPalliation in majority of cases Majority are malignantMajority are malignant Resection of primary and mesenteric Resection of primary and mesenteric

lymph nodes despite liver metslymph nodes despite liver mets– For cure / delay progression (could For cure / delay progression (could

endanger small bowel)endanger small bowel)– Can alleviate symptomsCan alleviate symptoms– ? Prolong survival ? Prolong survival

Symptomatic TreatmentSymptomatic Treatment

Used in patient with secretory symptomsUsed in patient with secretory symptoms Somatostatin analogues (e.g. Octreotide)Somatostatin analogues (e.g. Octreotide)

– Inhibits release of many hormonesInhibits release of many hormones– Can impair some exocrine functionsCan impair some exocrine functions

Hormone response in 30-70% patientsHormone response in 30-70% patients Symptom control in majoritySymptom control in majority Rarely tumour shrinkageRarely tumour shrinkage

Additional medicationAdditional medication

Ondansatron Ondansatron – nauseanausea

CyproheptadineCyproheptadine CholestyramineCholestyramine CREONCREON

– Control of diarrhoea, esp after intestinal Control of diarrhoea, esp after intestinal resectionresection

Interferon alphaInterferon alpha

Sole use or with somatostatin Sole use or with somatostatin analoguesanalogues

? Efficacy (conflicting evidence)? Efficacy (conflicting evidence) Some evidence better in tumour with Some evidence better in tumour with

low mitotic rateslow mitotic rates Biochemical response 40-60% Biochemical response 40-60% Symptomatic improvement 40-70%Symptomatic improvement 40-70% Significant tumour shrinkage 10-15% Significant tumour shrinkage 10-15%

Other optionsOther options

Chemotherapy Chemotherapy – Role uncertain but being actively Role uncertain but being actively

researchedresearched– Response short lived (8-10 months)Response short lived (8-10 months)

Hepatic artery embolisationHepatic artery embolisation– Indicated for non resectable & multiple Indicated for non resectable & multiple

hormone secreting tumourshormone secreting tumours– Causes ischaemia of tumour cellsCauses ischaemia of tumour cells– Symptomatic response 40-80%Symptomatic response 40-80%– 5 year survival 50-60%5 year survival 50-60%

Radionucleotide therapyRadionucleotide therapy– Palliative optionPalliative option– Exploits increased uptake of Exploits increased uptake of

radiolabelled isotopes I-MIBG or radiolabelled isotopes I-MIBG or octreotideoctreotide

– Symptom control 80%Symptom control 80% Radiotherapy Radiotherapy

– Carcinoid – radioresistantCarcinoid – radioresistant– Relief of pain from bone metsRelief of pain from bone mets

PrognosisPrognosis

No TNM classificationNo TNM classification Slow growing, but survival depends Slow growing, but survival depends

on on – Histological type Histological type – Degree of differentiationDegree of differentiation– Mitotic rateMitotic rate– Tumour sizeTumour size– Depth and locationDepth and location– Lymph node/ liver metastasesLymph node/ liver metastases

Prognosis – 5 year survivalPrognosis – 5 year survival