Title: Aucun titre de diapositive
1Management of pancreatic endocrine tumors
Guillaume Cadiot Reims
2Different types of endocrine tumors of the
duodeno-pancreatic area
Type Incidence
(per million) Insulinoma
1-2 Zollinger-Ellison 0,5-1,5 VIPom
a 0,05-0,2 Glucagonoma
0,01-0,1 Somatostatinoma Very
rare Non functioning ?
3Endocrine tumors of the duodeno-pancreatic area
Liver mets MEN1 () () Insulinomas 10 5-8 ZES
25 25 VIPomas 25 10 Glucagonomas gt 50 lt
5 Somatostatinomas 50 lt 5 Non functioning ? ?
4(No Transcript)
5Plan
1- Think to the diagnosis 2- Control functioning
syndrome 3- Confirm the diagnosis 4- Search for
MEN 1 5- Extension assessment 6- Specific therapy
6Plan
1- Think to the diagnosis 2- Control functioning
syndrome 3- Confirm the diagnosis 4- Search for
MEN 1 5- Extension assessment 6- Specific therapy
7Signs at diagnosis
- Functioning tumors
- functioning signs
- liver metastases
- Non functioning tumors
- signs due to the size or location of the tumor,
liver metastases - fortuitous
8Signs of the endocrine tumors of the
duodeno-pancreatic area
Type Functioning
symptoms Insulinoma
Hypoglycemia Zollinger-Ellison Ul
cers, diarrhoea VIPoma Diarrhoea
Glucagonoma Cutaneous,
diabetes Somatostatinoma Diarrhoea,
diabetes Non functioning None
9Zollinger-Ellison syndrome
Duodenal ulcer
Esophagitis
Diarrhoea
- Complicated
- Resistant
- Beyond 1st duod
- Recurrence after HP eradication
- HP/NSAIDs neg
- Frequent
- Reduced by PPI
- Isolated (3)
- Vomitting
- Weight loss
- Kydney stone
10(No Transcript)
11Plan
1- Think to the diagnosis 2- Control functioning
syndrome 3- Confirm the diagnosis 4- Search for
MEN 1 5- Extension assessment 6- Specific therapy
12Plan
1- Think to the diagnosis 2- Control functioning
syndrome 3- Confirm the diagnosis 4- Search for
MEN 1 5- Extension assessment 6- Specific therapy
13Diagnosis of functioning PET
- Peptide measurement
- Not enough in ZES
14Main causes of hypergastrinemia
15Hypergastrinemia and pernicious anemia
N
Sjöblom et al. Gut 1993
16Basal gastrinemia DU vs ZES
Bichat series
17H. pylori-related DU with hypergastrinemia and
high BAO
David Metz et al. Dig Dis Sci 1995
18Secretin test (3 U/kg/h infusion)
94 of ZES patients gt 1 specific criteria at
99-100
19Biochemical investigations. Pancreatic
tumor French recommendations
- REFERENCE
- If functioning tumor dosage of the specific
peptide - dynamic test (secretin test, prolonged fast)
- Glycemia, calcemia, phosphoremia
- PTH
- Chromogranin A
- ALTERNATIVE
- Â All peptidesÂ
20Chromogranin A Sensibility in pancreatic
endocrine tumor
72
8
0
52
45
6
0
35
C
g
A
4
0
N
S
E
2
0
0
Functioning
Non functioning
Baudin et al. Ann Oncol 2001
21Chromogranin A
- Sensibility small tumor low ??
- Specificity pancreatic tumor
- CgA 70
- NSE 100
- Correlation between evolution of CgA levels and
that of tumor mass
22Plan
1- Think to the diagnosis 2- Control functioning
syndrome 3- Confirm the diagnosis 4- Search for
MEN 1 5- Extension assessment 6- Specific therapy
23Prevalence of MEN 1
MEN 1 () ZES 25 Insulinoma 5-8 VIPoma 10 Gluca
gonoma lt 5 Somatostatinoma lt 5 Non functioning
tumors ?
M Mignon et al
24MEN 1 assessment French recommendations
- Reference
- Only if stomach (and ZES), duodenum, pancreas
- Search for symptoms in patients and relatives
- Basal ionized calcium levels and PTH levels
- Large suspicion of MEN 1 or high risk
conditions dosage of all peptides, MEN 1 gene
mutations, imagery (pituitary, adrenals, chest)
25ZES MEN 1 other endocrinopathy frequency
other series
26Plan
1- Think to the diagnosis 2- Control functioning
syndrome 3- Confirm the diagnosis 4- Search for
MEN 1 5- Extension assessment 6- Specific therapy
27Extension assessment
- Searching primary tumor(s)
- Searching liver metastases
- Synchronous 24
- Metachronous 6 (mean F-U 9 years)
data for ZES
28Primary tumors Sporadic ZES (75)
- Unique except associated lymph nodes
- 65 duodenum and/or lymph nodes
- 25 pancreas lymph nodes
- 10 not found
- Duodenal gastrinoma lt 1 cm 77
- Pancreatic gastrinoma gt 3 cm 73
29Primary tumors ZES and MEN 1 (25)
- Multiple
- Duodenum gt 80 (gastrinomas)
- Pancreas gt 80 (gastrinomas 20 ?)
- Small 90 pancreatic tumors lt 3 cm
30French recommendations
- Initial morphological explorations
- Abdominal ultrasound
- Abdominal and pelvic CT-scan
- Somatostatin receptor scintigraphy
- Endoscopic ultrasonography (stomach, duodenal,
pancreatic tumors)
31Localization of duodeno-pancreatic tumors
Duodenum - EUS 50 Pancreas - EUS
75-100 - CT-scan, MRI 60-85
(mean tumor size 2 cm) Octreoscan - gt
15-20 mm 90-100 - lt 15 mm 40
32Endoscopic ultrasonography of the pancreas in MEN
1
Isoechogenic small pancreatic tumor
Lymph node
Hyperechogenic small pancreatic tumor
Hypoechogenic small pancreatic tumor
Thomas-Marques et al. Am J Gastroenterol 2005 (in
press)
33Insulinoma
34Gastrinomes duodénaux
35Sporadic Zollinger-Ellison syndrome
Posterior view
Lymph node
Lymph node
Duodenal gastrinoma
Lymph node
36RT Jensen, NIH
37Detection of duodenal gastrinoma and lymph
nodes Cadiot et al. Gastroenterology
1996111845-54
- All Duodenum Lymph nodes
- gastrinomas (n8) duodenum
- (n19) (n11)
- EUS 11Â (58) 5 (63) 6 (55)
- SRS 11Â (58) 3 (38) 8 (73)
- EUS SRS 17Â (90) 7 (88) 10 (91)
Lymph nodes duodenum (n5) US and CT-scan
always negative
38Detection of liver metastases (gastrinoma) Gibril
et al. Ann Intern Med 199612526-34
46
42
71
62
83
92
96
12
4
0
25
50
75
100
Percentage of positive patients
39Liver metastases
40Magnetic resonance imaging Endocrine liver
metastases
41Bone metastases
42Plan
1- Think to the diagnosis 2- Control functioning
syndrome 3- Confirm the diagnosis 4- Search for
MEN 1 5- Extension assessment 6- Specific therapy
43Sporadic pancreatic endocrine tumor
Surgery, even when tumor is invasive, except
contra-indications due to poor condition
44Surgery in MEN 1 ?
45Development of liver metastases according to
primary tumor size
No pancreatic tumor
Pancreatic tumor lt 3 cm
Pancreatic tumor gt 3 cm
77 patients with ZES and MEN 1
Cadiot et al. Gastroenterology 1999
46Risk of metastases according to non-functioning
PET size
Triponez, GTE, Ann Surg 2005
47Life expectancy
P 0.33
No pancreatic tumorNFPET 2 cm
Cumulative survival
Age
48Indications for surgery in MEN 1 ?
- All functioning tumors except ZES
- For ZES and non-functioning tumors
- Tumor size gt 2 cm or increasing size assessed by
EUS - Probably take into account liver metastases in
first degree relatives
49Which operation ?
50(No Transcript)
51Insulinoma
- Hypoglycemia
- Sporadic tumor (not MEN 1-related) (95)
- Single, small
- Pancreatic (99)
- Benign (90)
52VIPoma
- Diarrhoea often profuse (gt 5 litres 37 )
- Déshydratation, troubles ioniques
- Diarrhée intermittente (50)
- Flushs (23 )
- Elévation de la VIPémie
- Tumeur pancréatique (84 ), gt 3 cm (78 ),
maligne (50 ), sporadique (gt 85)
53Glucagonome
- Erythème nécrolytique migrateur (90 )
- Amaigrissement massif (96 )
- Diabète (87 )
- Manifestations thrombo-emboliques
- Anémie normochrome normocytaire (40)
- Hyperglucagonémie franche
- Tumeur unique, grosse, maligne, sporadique
- Tum. asymptomatiques hyperglucagonémie ?
54Glucagonome Erythème nécrolytique migrateur
55Somatostatinome Vinik et al Sem Oncol
198714263-81
Pancréas Duodénum (n27) (n21) Diabète 21/27 3
/14 Lithiase vésiculaire 17/18 6/14 Diarrhée 11/12
3/8 Stéatorrhée 10/12 1/8 Amaigrissement 9/10 4/9
Ictère - 3/9 Siège Tête, corps Ampullaire
5 Métastases Foie 19/23 3/16
56Autres tumeurs fonctionnelles exceptionnelles !
- GRF
- ACTH
- Sérotonine
- Thyrocalcitonine (fonctionnelles ?)
- PTHrp