Carcinoid Tumours / NET
Tumours mostly of the GI tract, which secrete bioactive peptides
resulting in a number of endocrine syndromes, including carcinoid Syndrome.
Carcinoid = "carcinoma-like"; this because of relatively indolent
nature cf carcinoma.
Preferred term is now
Neuroendocrine Tumours ("NET") (WHO)
Formerly also APUDoma
See also pancreatic neuroendocrine tumours
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Peaks in 50s.
But can occur at any age.
Increasing; possibly due to better diagnosis.
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Diverse range of slow-growing neoplasms from enterochromaffin
- these cells are normally found throughout the crypts of
Most commonly GI origin, occasionally in other organs, eg lungs,
thymus, biliary tree, testicles or even liver.
- Of GI carcinoids, commonly in small intestine (45%), also appendix
(>10%), less likelihood in stomach, colon and rectum
- 1/3 of intestinal ones are multi-centric, others tend to be
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Cells making peptide and non-peptide bioactive hormones are found
along the entire GI tract normally.
- are derived from endothelial cells, but called 'endocrine' because
of their function and resemblance.
Synthesise and secrete a variety of bioactive peptides.
- serotonin is most common
- multiple factors may also be synthesised by a single tumour
- but more likely to produce a predominant clinical syndrome, eg
gastrinoma, somatostanoma, insulinoma.
- with GI carcinoids, liver metabolises products, so hepatic mets
must exist before symptoms.
All are potentially malignant
- average size at presentation is <2cm
- and up to 50% have spread by diagnosis
Tendency for aggressive behaviour correlates to:
- site of origin
- depth of local penetration
Eg appendiceal and rectal carcinoids less likely to metastasize (but may show extensive local
Mesenteric nodal spread is otherwise common.
5-year survival is 90%
- >50% with small bowel tumours and hepatic mets
- widespread disease is however rarely curable
In appendix, tend to be bulbous swellings of the tip
Elsewhere they can be polypoid elevations rarely over 3cm.
- characteristically yellow-tan on transection.
Visceral mets are usually small and dispersed.
Cells arranged in islands / glands or sheets etc, and are fairly
regular in most cases.
Mets favour liver
- thereafter, bone, lungs, CNS, many possible locations.
Agarophilia; serotonin stains with silver
May induce stricturing or kinking sufficient to induce obstruction.
can cause shortening of mesentery, fixation of mesentery to
- often a cause of the kinking
- this is because involvement of serosa causes an intense
- due to infiltration and local release of serotonin and other
--> fibrosis may cause venous congestion and ischaemia
May encase retroperitoneal
vessels if severe
- venous stasis and venous ischaemia
Produce a variety of symptoms dependent on site and type of
bioactive amine produced.
- zollinger-ellison syndrome
from excess gastrin.
- cushing's syndrome
Presentation in 10% of patients
- or 20% of those with widespread mets
Most arise from excess 5-hydroxytryptamine (5-HTP) secretion
- also produce histamine, bradykinin, kallikrein, prostaglandins;
virtually any vasoactive
Generally (not exclusively) requires liver mets; avoids clearance of
tumour secretions by liver
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Grow slowly in intestine wall so often asymptomatic at first.
Can have a prolonged history of vague pains, cramping, distension,
nausea and vomiting, diarrhoea and weight loss,
Possibly might obstruct, bleed or become ischaemic
Features of endocrinopathies above.
- may be provoked by stress, coffee, aged cheese, alcohol
vomiting (most), diarrhoea, food / alcohol intolerances
wheeze, dyspnoea (1/3)
Systemic fibrosis: heart,
lung, retroperitoneal fibrosis, collagenous pleural / intimal
- heart disease (2/3 untreated) --> fibrous cardiac plaques,
pulmonary stenosis or tricuspid regurge.
--> responsible for 50% deaths in these pts.
Excessive flushing, hyperthermia, shock, arrhythmia, bronchial
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30-50% simply found at laparotomy as a cause of bowel
But its metabolite 5-HIAA
(5-hydroxyindoleacetic acid) is measured
- 24 hr urinary collection
73% sensitive, 100% if liver mets; very specific.
Chromogranin A blood level
- chromogranins are neuroendocrine markers; glycoprotein released by
- superior screening test.
- sensitivity >80%, but specificity decreased by atrophic
gastritis, renal impairment, IBD, PPIs
- but currently requires pt consent as they have to pay in Aus.
- also used for disease monitoring and surveillance for recurrence.
- primaries are often small and not readily seen; good for
examination large masses and resectability
- mesenteric lesions highly suggestive, with calcification in 50%
- contrast can help inform extent and resectability
- role of MRI more restricted to assessing possibility of liver
--> tumour necrosis may give lesions a rim-pattern of
Ocreatide scan; sensitivity 80-90%
- ie '
somatostatin receptor scintigraphy'
Routine used to identify degree of
Also helps to predict response to treatment
with somatostatin receptor analogs (ocreotide)
Less of a role in well differentiated tumours
But can be used with special neuroendocrine markers
eg labeled HTP
Feasible for duodenal carcinoids
Perform on all patients with carcinoid syndrome
To rule out synchronous disease, going well into TI if possible.
- increasingly, double-balloon enteroscopy being used to assess SB
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Treatment depends on size, location and symptoms
Tumours <1cm are generally benign
1. Assess extent of local and distal disease
2. Identify synchronous and non-synchronous carcinoid tumours
- need to exclude concurrent adenoCa; 10-15% in this group
3. Fluid and electrolyte repletion
4. Pharmacologic treatments
5. Detect cardiac abnormalities
Prophylactic measures against
Can be precipitated by operative stress
All at risk, though much higher in carcinoid syndrome
1. Give peri-operative somatostatin analogs (ie ocreotide); 100ug
2. Carcinoid crisis can be treated with bolus IV ocreotide (100ug IV
push), followed by ocreotide infusion, antihistamines,
hydrocortisone, and albuterol as reqd.
Surgery is most effective therapy when possible.
- relieves obstruction bleeding and secretory effects
Metastatic nodal spread is common
--> requires extensive lymphadenectomy and wide resection of the
--> carefully inspect abdomen for multicentric lesions and liver
May be extremely difficult to find.
Small lesions can be removed endoscopically.
- ie <1cm unless there is evidence of lymph node mets by imaging
1-2 cm may require transduodenal excision (if no nodes)
Larger lesions should be surgically removed until short life
expectancy or widespread metastatic disease.
- if close to ampulla, pancreaticoduodenectomy may be required.
- if localised resectable disease in liver, resect all.
- resection helps to minimize chance of complications such as
Jejunum / ileum
Many present with obstruction and should undergo limited bowel
resection and wedge excision of mesentery.
May be a small mass with large mass in mesentery and fibrosis
Want to take nodes high, up to around the SMA +/- its branches
- radical resection not possible if SMA surrounded by fibrotic
reaction, do not want infarction and short gut post op
- unless close to end of ileum, in which case it should be possible
to do a limited ileocolic resection
Evaluate rest of bowel carefully for additional lesions
Should be considered if unresectable because many patients on
long-term long-term somatostatin analogs will develop problematic
Appendiceal NETs review (BJS 2003):
1. lesions at the base of the appendix with tumour-positive margins
2. mesoappendiceal invasion
3. any high-grade malignant carcinoid (including those with a high
4. 2 cm in size (up to 30% chance of mets if >2cm; vs ~0% chance
5. atypical goblet cell adenocarcinoids (do not express somatostatin
Examine every 3m for 1y
- hx, exam +/- tumour markers +/- scans
Then every 6m from 2-5y
- yearly thereafter
Management of Metastatic Disease
50% of pts seen initially will have liver disease
There are liver mets:
Resect the primary tumour anyway, to prevent later local
Resection of liver mets is the gold standard treatment.
- must have resectable disease with acceptable remnant liver,
inflow, outflow, biliary drainage; 2 stage procedures acceptable
- and acceptable comorbidities, including lack of R heart
- and no diffuse carcinomatosis
Other options for liver mets, if not all surgical resectable,
include ablation, embolization, transplantation (may be in
combination with surgery)
- RFA most common approach; can be delivered under radiological
- but not for large tumours or those close to vital structures
- TACE is also affective, as liver met course is predominantly
--> effective control achieved in 50% through selective use of
Resection of bowel, mesentery, nodes, hepatic mets and fibrosis may
all improve quality of life.
- debulking ok, including with liver resection, but would need to
eradicate / debulk most of it to achieve effective palliation; makes
drugs more effective.
- aggressive resections may
Transplantation is reasonable in selected patients with fulminant
- but long-term survival is exceptional.
Long-Acting Somatostatin Analogs
Highly effective in symptom control; response rate ~60%
- stabilization of progression may also be seen in ~1/3
Depot administrations can be given every 4 weeks
Side effects can include abdo discomfort, gallstones, malabsorption
Monitor response with urinary 5-HIAA, plasma serotonin, plasma
Interferons second line therapy
Chemo efficacy is very limited.
Promising, may soon become treatment of choice in advanced disease
Treatment response in up to a third, often for >2 years
Depends on how reactive tumour is with SRS
5-yr survival is ~60% but 'stage' dependent
- 90% for good down to 40% for bad.
- there is actually no formal staging system, tumours are lumped by
extent of spread.
Age >55, male, tumour primary >1cm, distant mets, positive
Yes. 85% will ultimately develop liver mets.
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