Endocrine tumors of the
gastrointestinal tract
Dr n med. JacekPytel
Endocrine tumors of the
gastrointestinal tract
• In 1902 secretin was discovered by Bayliss and
Starling
• Among the cells covering the gastrointestinal
tract are single cells with characteristic typical
endocrine cells
They create a kind of "diffuse"endocrine organ scattered intraepithelial endocrine glands
Endocrine tumors of the
gastrointestinal tract
• Thanks to cytochemicalimunohistochemistry- and fluorescent
reactions presence of these glands in the
epithelium were found in
gastrointestinal tract and in the islands of
Langerhans of pancreas, adrenal medulla,
bronchial epithelium, fallopian tubes,
vagina and uterus
Endocrine tumors of the
gastrointestinal tract
• These cells are characterized by the ability
to capture and metabolize biogenic amines
and their precursors, and synthesizing small
molecule and peptide hormone secretion
Endocrine tumors of the
gastrointestinal tract
• Properties:
Amine precursor uptake and
decarboxylation
APUD
Endocrine tumors of the
gastrointestinal tract
• APUD system cells origin from
neuroectoderm and migrate to the mucosa
of primitive gut and the buds of future organ
in embryonic development
Endocrine tumors of the
gastrointestinal tract
• This same origin as the cells of the nervous
system, chemoreceptors cells, adrenal
medulla cells
Endocrine tumors of the
gastrointestinal tract
• Digestive tract there are a lot of active
peptides
gastrin, secretin, cholecystokininpancreozymin (CCK-PZ) - classified as
hormones - regulate physiological functions
of the gastrointestinal tract
Endocrine tumors of the
gastrointestinal tract
• The epithelial cells of gastrointestinal tract
and pancreatic endocrine function
displaying can develop cancer of a
APUDoma
They can be „silent” or produce
characteristic symptoms of hormone
secretion
Endocrine tumors of the
gastrointestinal tract
• The incidence 5-20 cases per million
population per year
• In about 70% of patients have the
syndrome of multiple endocrine tumors type
I
(Multiple Endocrine Neoplasia - MEN)
• Hormonally inactive tumors - significantly
more
Endocrine tumors of the
gastrointestinal tract
• 3% of pancreatic cancers - neuroendocrine
tumors (ca. 76% - hormonally inactive)
• Resective in approximately 76% (pancreatic
cancer 19%)
• 30-50% located outside the pancreas
• About 50% - malignant
Endocrine tumors of the
gastrointestinal tract
• Treatment aimed at inhibiting grow tumor
and reduce the excessive production of
hormones
• Somatostatin analogs effectively control the
secretion of hormones
• The therapeutic target for tumor treatment
Endocrine tumors of the
gastrointestinal tract
• 80-90% of neuroendocrine tumors has
somatostatin receptor
Somatostatin analogues (octreotide,
lanreotide, RC-160)-for treatment,
Diagnostics - marked octreotide - to
scyntygraphy
Endocrine tumors of the
gastrointestinal tract
• Endocrine tumors serotonin capture
(precursor 5-hydroxytryptophan)
PET (positron emission tomography - PET)
for locating small changes
undetectable by scyntygraphy use octreotide
Endocrine tumors of the
gastrointestinal tract
Diagnostics
• Angiography of the celiac trunk
• USG
• Computed tomography CT
• MRI Magnetic resonance tomography
• Scyntygraphy (isotope indium-labeled
octreotide (In111)
• Endoscopic Ultrasonography - EUS
Endocrine tumors of the
gastrointestinal tract
Diagnostics:
- Arterial stimulation venossus sampling
ASVS
- Transhepatic portal venosus sampling
THPVS
- Intraoperative usltrasonography
- Intraoperative hormone measure
Endocrine tumors of the
gastrointestinal tract
• 20-60% insulinomas fails to specify the
position before the operation
10-20% intraoperatively (experienced
surgeon - 90% of the palpable sense)
Endocrine tumors of the
gastrointestinal tract
• Treatment:
chemotherapy: streptozotocin and 5
fluorouracil, doxorubicin, cispaltyna (partial
remission for about two years 40-60%)
Interferon alpha - 50% biochemical response,
tumor reduction 20%
Somatostatin analogues (octreotide),
symptomatic and biochemical response 3575%
Endocrine tumors of the
gastrointestinal tract
• Treatment: There is no uniform pattern of
diagnostic and therapeutic
- Removal of the tumor or tumors
- Liver metastases - arterial embolization,
liver transplant!
Endocrine tumors of the
gastrointestinal tract
• treatment:
- Radiation therapy - tumors generally
resistant to radiotherapy
- Isotope-labeled somatostatin analogue
itrium (Y90)
Insulinoma
• 1869-Langerhans - described the pancreatic
insulas
Insulinoma
• 1902 - Nicholls described a pancreatic
endocrine tumor cells
• The incidence of approx. 0.5-5 / 1 million
persons / year
• The most common tumor causing
hypoglycemia
• Other tumors - beyond the pancreas insulin-secreting growth factors (IGFinsulin-like growth factors)
Insulinoma
• 60% of all pancreatic insulomas
Tumor diameter 5-60 mm aprx. 20 mm
90% of cases does not exceed 20 mm
10% of multiple endocrine syndrome (MEN
1)
10-15% of malignant
Insulinoma
Clinical symptoms:
Whipple’ triad
- occurrence of spontaneous hypoglycemia
- low blood glucose levels below 50 mg%
- regression of hypoglycemia after oral or
intravenous administration of glucose
Insulinoma
• Treatment of choice - surgery
Insulinoma
• Approximately 70% of patients after
surgery recover
• Perioperative mortality rate is 10%
• In the case of malignant changes in the
average survival time is about 2 years
Insulinoma
Ultrasonografia przedoperacyjna
Insulinoma
Ultrasonografia przedoperacyjna
Tomografia komputerowa
Insulinoma
Tomografia komputerowa – guz w głowie trzustki
Insulinoma
Ultrasonografia śródoperacyjna
Guz o średnicy 13 mm na pograniczu głowy i trzonu trzustki
Insulinoma
Ultrasonografia śródoperacyjna
Dobrze odgraniczony guz o średnicy 10 mm w okolicy wyrostka haczykowatego
Insulinoma
Złośliwy guz naciekający śledzionę, liczne przerzuty w wątrobie
Insulinoma
Mały guz ostro odgraniczony od miąższu trzustki
Insulinoma
Mały guz trzustki – 21 mm
Insulinoma
Ultrasonografia endoskopowa
Insulinoma
Ultrasonografia endoskopowa
Insulinoma
Laparoskopia
Gastrinoma
• Gastrinoma - a tumor, which causes gastrin
releasing hypergastrinaemia and increased
gastric acid secretion
Tumors: ovarian cancer, bronchial carcinoid
may secrete gastrin, but in such quantity
that do not cause hypergastrinaemia
Gastrinoma
• In1955 Zollinger and Ellison described a
syndrome:
• - Persistent, recurrent ulcers stomach or
duodenum, even after partial gastric
resection and vagotomy
• - Excessive basal secretion of gastric acid
• - The presence of pancreatic cancer island
cells derived from D
Gastrinoma
• Frequency of gastrinoma 0.5-10 / 1mln/per
year
• About 0.1% of patients with peptic ulcer
disease
Gastrinoma
• Excessive production of gastrin by tumors derived
from not beta-cell (G cells) pancreatic islet
• 70% malignat tumors
• In 20% of single tumor
• Often develop slowly and multifocuses
• Metastasis in to lymph nodes and liver but rarely
to the lung.
• In about 20% occur in MEN I syndrome
Gastrinoma
Zolliner Ellison Syndrom:
-The presence of multiple peptic ulcers in the
esophagus, stomach or duodenum
-Hipersecretion gastrc acid
-The presence of pancreatic tumor secreting
gastrin
Gastrinoma
Symptoms:
- Abdominal pain associated with active
peptic ulceration or perforation in the
course of morbus ulcerosus
- Diarrhea caused by excessive production of
gastric juice
- Tarry stools due to bleeding from the upper
gastrointestinal tract
Gastrinoma
The symptoms and laboratory results gives rise to a suspicion
of ZES:
-Recurrent peptic ulcer disease resistant to treatment
-Basal secretion of gastric juice above 15 mmol HCl /h
-Ratio of primary to a maximum of gastric acid secretion
(BAO: MAO) does not exceed 0.6
-Gastrin concentration in serum above 500 pg / ml (normal up
to 200 pg / ml)
- In tests with intravenous administration calcium, glucagon,
or secretin in patients with ZES showed an increase in
gastrin
Gastrinoma
Treatment
The basic goal
Inhibition of gastric acid secretion with high acidity
by surgery
Tumor resection
Not always possible
Ectopic placement
metastases
Total gastric resection
Multifocus changes
Gastrinoma
Prognosis
In the case of ZES good provided hypersecretion and eradicate gastric
hyperacidity
Malignant neoplasms in many cases - may grow slowly
Survival can be long
Gastrinoma
Vipoma
Vernera-Morrisona Syndrom (1958), WDHA – watery
diarrhea hypokalemia achlorhydria
Tumor derived from pancreatic islet beta produced vasoactive
intestinal hormon, often malignant, usually single, 80% of
pancreatic APUDoma
Clinical symptoms
•persistent watery diarrhea (more than 3l / d)
•symptoms of hypokalaemia
•asthenie
achlorhydria
•Tetany (as a result of hypomagnesaemia)
WDHA syndrom diagnosed very rare o
Pure prognosis
Vipoma
Liczne przerzuty w wątrobie
Vipoma
Tomografia komputerowa
Glukagonoma
The tumors derived from pancreatic islet alpha cells secrete glucagon,
about 70% is malignant, approximately 100 cases yet documented in
the world
Clinical symptoms
•hiperglikemia
•skin lesion - erythema migrans with necrosis places
•stomatitis
•hemolytic anemia
•elevated glucagon levels above 500 pg / ml
diagnosis - Clinical signs + pancreatic tumor
Glukagonoma
Glukagonoma
Somatostatinoma
The tumors associated with tumor cell proliferation delta pancreatic islet
•are extremely rare
•large virulence
•previously documented in the world only a few dozen cases
Diagnosis and treatment is the same as in other pancreatic tumors
derived from the APUD system cells
Somatostatinoma
Carcinoid
• WHO classification term - carcinoid replaced - neuroendocrine tumors
Carcinoid
• 0,5-2,1 / 100 000 persons per year - on
alimentary tract
• 0.3 / 100 000 persons per year - bronchus
Carcinoid
Carcinoid
85% alimentary tract
- appendix 44%
- rectum 15%
- ileum 11%
10% lungs
30% non malignat tumors
Carcinoid
The incidence of
-appendix
- rectum, ileum
tumor below in diameter
1 cm
2 cm
metastase
2%
80 %
Slow growth - 5-year survival in
more than 70% of operated
patients
Carcinoid
• Carcinoid - of I part of the primitive gut
(respiratory system, thymus, stomach,
duodenum)
- Usually secrete corticotropin-CRH,
ACTH, somatolibertin (growth-releasing
hormone-GH-RH), serotonin, gastrin,
glucagon
Carcinoid
• Carcinoid tumors of the second part primary
gut (ileum, colon ascendens) usually secrete
serotonin, tachykinins, bradykinin,
chromogranin A
The final part of the primary gut (colon,
rectum) are often hormonal inactive, can
produce chromogranin A, human chorionic
gonadotropin
Carcinoid
Clinical symptoms
Carcinoid syndrome is caused by the action of vasoactive
substances - serotonin
•flush
•diarrhoea
•bronchospasmus - rare
•damage to the right side of the heart valves
Carcinoid
• Carcinoid crisis) in patients with
metastatses, usually to the liver. Usually
after induction (biopsy, surgery) - a
significant drop in pressure, feeling beat and
palpitations, massive watery diarrhea,
shortness of breath, abdominal cramps,
asthma attacks, flushing of the face, neck,
upper part, hyperthermia
Carcinoid
• Carcinoid crisis- a life-threatening
condition.
Requires intensive treatment.
- Octreotide 100 micro grams
- Histamine receptor blockers
Carcinoid
• Cardiac symptoms (carcinoid heart disease)
- subendocardial deposition of collagen –
thickening, distortion and narrowing of the
tricuspid valve and pulmonary trunk
Carcinoid
Treatment
Extensive excision of the primary tumor and regional lymph nodes
In the case of liver metastases
hepatic artery embolization
Adjuvant treatment - cytostatics
Symptomatic treatment - serotonin inhibitors (cyproheptydyna),
somatostatin analogues
Rakowiaki
Klinika Chirurgii Endokrynologicznej i Ogólnej UM w Łodzi
1974 - 2005
Apendektomie
3371
zagięcie śledzionowe
okrężnicy
1
guz śr. 120 mm
Hemikolektomie
512
jelito cienkie
1
guz śr. 30 mm
wyrostek robaczkowy
4
guzy o śr. od 5 do 15 mm
krezka jelita cienkiego
1
guz śr. 35 mm był przyczyną
martwicy jelita cienkiego
Rakowiak jelita cienkiego
Rakowiak oskrzela
Rakowiak oskrzela – obraz endoskopowy
Rakowiak wyrostka robaczkowego
Rakowiak jelita
Rakowiak jelita
Przerzuty do węzłów chłonnych