1. Neuroendocrine Tumours

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

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

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

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

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

7. 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)

8. Diagnosis Clinical symptoms Hormone concentrations Radiology
Histology – gold standard

9. 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

10. 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

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

12. 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

13. 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

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

15. 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%

16. 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%

17. 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

18. 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

19. Prognosis – 5 year survival