- Most common
gastrointestinal endocrine tumor (75% of such neoplasms)
- Presenting
symptoms:
- Gastrointestinal bleeding
- Abdominal pain
- GI obstruction due to:
- tumor growth
- tumor-induced
mesenteric fibrosis
- Symptoms associated with
hormones secreted by the tumor
- Carcinoid refers to tumor
slow growth (4-5 years between onset of symptoms
and diagnosis) and initial underestimation of
malignant potential.
- Tumor properties:
- Arise from
neuroendocrine cells {neuroendocrine cells are
most common in: the gastrointestinal
tract, pulmonary bronchi, pancreas}
- Tumors are most
commonly found in the appendix, ileum,
and rectum (may
be found anywhere from the stomach to the
rectum)
- In the small
intestine: carcinoid tumors -- one of the
two most common malignancies.
- 90% of
carcinoid tumors derived from
enterochromaffin (Kulchitsky cells)
within the gastrointestinal tract
- From a small, primary
tumor, peritoneal and mesenteric spread
induces by fibrotic reactions (causing obstruction,
vascular compromise, intestinal kinking)
- Gastric
carcinoid tumor may arise from:
- enterochromaffin
cells or
- histamine-secreting enterochromaffin-like cells
- increased
risk factors for this etiology:
- chronic
atrophic gastritis
- tumorigenesis
due to the combination of
chronic inflammation and
hypergastriemia
associated with atrophic
gastritis.
- achlorhydria
due to:
- pernicious
anemia
- Helicobacter
pylori infection
- Carcinoid
Syndrome:
- Enterochromaffin cells:
- embryologically
related to:
- thyroid C
cells
- adrenal
medullary cells
- melanocytes
- secrete
many hormones, causing symptoms
of hormone excess, including:
- cutaneous
flushing, diarrhea,
valvular heart disease (endocardial
fibrosis --tricuspid
insufficiency, pulmonary
stenosis, right-sided
heart failure}"classic
triad"
- (less
commonly): wheezing,
paroxysmal hypotension,
telangiectasis (spot
formed on the skin by a
dilated capillary or
terminal artery)
- Serotonin:
most common secretory product (tumor
serotonin synthesis from circulating tryptophan)
- up to 50%
of dietary tryptophan may be
converted to serotonin by the
tumor, leading insufficient amino
acid substrate for protein
synthesis and conversion to
niacin. Consequently:
- patients
may exhibit protein
malnutrition or
- mild
pellagra
- (niacin
deficiency -- erythema on
portions of the body
exposed to light,
subsequent dermal
exfoliation;also,
weakness, digestive
disturbance, spinal pain,
convulsions, melancholia)
- Diagnosis:
- abdominal pain,
nausea, weight loss, obstruction,
gastrointestinal bleeding
- imaging studies
(CT, barium studies)
- endoscopy
- Most
useful diagnostic test:serotonin
metabolite (urinary
5-hydroxyindoleacetic acid
{5-HIAA} concentration -- > 15
mg per day
- plasma and
platelet serotonin levels
- biopsy
- octreotide
scintigraphy (octreotide binds to
type 2 somatostatin receptors
(highly expressed by most carcinoids)
- Treatment:
- tumor
resection (rarely curative due to
metastasis)
- loperamide, diphenoxylate/atropine
for mild diarrhea:
- cholestyramine
(Questran, Questran
Light)(following ileal resection)
- H1
and H2 receptor
blockers (e.g. diphenhydramine
and ranitidine)-- inhibit
cutaneous flushing.
- phenoxybenzamine (Dibenzyline)--
inhibition of bradykinin release
- methylxanthine
bronchodilators and
glucocorticoids: relief of
dyspnea and wheezing due to
pulmonary carcinoids
- cyproheptadine
(Periactin) and methysergide
(Sansert): relief from diarrhea
- note that methysergide
can promote fibrosis
(similar to that caused
by the tumor)
- Octreotide:
potent inhibitor of carcinoid
hormone secretion. Effective in:
- treating
life-threatening
carcinoid syndrome
manifestations, e.g.:
- hypotension
with resulting angina.
- Transient
exacerbation due to
general anesthesia for
example.
- Systemic chemotherapy:
- streptozocin,
flurouracil (5-FU),
cyclophosphamide
(Cytoxan), and
doxorubicin (Adriamycin, Rubex, Doxil)--
- best response: combination
of doxorubicin and
streptozocin {tumor
regression in 40% of
patients}
- IFN-alpha
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