Copyright ©2008 The WJG Press and Baishideng.
World J Gastroenterol. Sep 21, 2008; 14(35): 5377-5384
Published online Sep 21, 2008. doi: 10.3748/wjg.14.5377
Table 1 WHO classification[12]
SiteWell differentiated endocrine tumor
Well-differentiated endocrine carcinomaPoorly-differentiated endocrine carcinoma
Pancreas< 2 cm≥ 2 cmLocal invasionSmall cells
< 2 mitoses1> 2 mitoses2-10 mitoses> 10 mitoses
< 2% Ki-67> 2% Ki-67> 5% Ki-67> 15% Ki-67
No vascular invasionVascular invasionVascular invasion ± metastasesVascular/perineural invasion
StomachMucosa/SubmucosaMucosa/SubmucosaInvasion of muscularis propria ± metastasesSmall cells
≤ 1 cm> 1 cm
No vascular invasionVascular invasion
Duodenum/Mucosa/SubmucosaMucosa/SubmucosaInvasion of muscularis propria ± metastasesSmall cells
Jejunum ≤ 1 cm> 1 cm
No vascular invasionVascular invasion
Ileum/Mucosa/SubmucosaMucosa/SubmucosaInvasion of muscularis propria ± metastasesSmall cells
Colon/ ≤ 1 cm (ileum)> 1 cm (ileum)
Rectum ≤ 2 cm (colon)> 2 cm (colon)
No vascular invasionVascular invasion
Appendix ≤ 2 cm> 2 cmExtensive invasion of mesoappendix ± metastasesSmall cells
No vascular invasionVascular invasion
Table 2 TNM staging for pancreatic NETs[13], foregut and midgut gastrointestinal carcinoids[14]
Pancreatic NETsForegut and midgut gastrointestinal carcinoids
T-primary tumor
TxPrimary tumor cannot be assessedPrimary tumor cannot be assessed
T0No evidence of primary tumorNo evidence of primary tumor
T1Tumor limited to the pancreas and size < 2 cmTumor invades mucosa or submucosa and size ≤ 1 cm
T2Tumor limited to the pancreas and size 2-4 cmTumor invades muscularis propria and size > 1 cm
T3Tumor limited to the pancreas and size > 4 cm or invading duodenum or bile ductTumor invades subserosa
T4Tumor invading adjacent organs (stomach, spleen, colon, adrenal gland) or the wall of large vessels (celiac axis or superior mesenteric artery)Tumor invades adjacent structures
For any T, add (m) for multiple tumorsFor any T, add (m) for multiple tumors
N-regional lymph nodes
NxRegional lymph nodes cannot be assessedRegional lymph nodes cannot be assessed
N0No regional lymph node metastasesNo regional lymph node metastases
N1Regional lymph node metastasesRegional lymph node metastases
M- distant metastases
MxDistant metastases cannot be assessedDistant metastases cannot be assessed
M0No distant metastasesNo distant metastases
M1Distant metastasesDistant metastases
Disease stage
IIIbAny TN1M0Any TN1M0
IVAny TAny NM1Any TAny NM1
Table 3 Carcinoid syndrome
Clinical featuresIncidence (%)CharacteristicsMediators
Flushing90Foregut tumors: prolonged fit, red-purple, localized to face and trunk. Midgut tumors: quick fit, pink-red.Serotonin, histamine, P substance, prostaglandins
Diarrhea70SecretorySerotonin, histamine, VIP, prostaglandins, gastrin
Abdominal pain40Long lastingObstruction, hepatomegaly, intestinal ischemia, fibrosis
Profuse sweating15Serotonin, histamine
Telangiectasias25FaceUnknown cause
Heart disease30 (right)Valvulopathies (tricuspid valve, pulmonary valve). Right heart failure. DyspneaP substance, serotonin
10 (left)
Pellagra5DermatitisDeficit of niacin
Table 4 Clinical features of the main endocrine pancreatic tumors
Tumor (syndrome)Clinical features and diagnostic testsMEN-1 (%)Metastases (%)SnSRS (%)
InsulinomaSpontaneous or fasting hypoglycemia (Whipple's triad)8-101050
Positive fasting test (hypoglycemia with hyperinsulinism)
Gastrinoma (Zollinger-Ellison syndrome)Peptic ulcers, diarrhea, GERD, BAO > 15 mEq/h306080
Positive secretin test (serum gastrinemia > 200 ng/L within 10 min from secretin venous infusion, 2 U/kg per min)
VIP-oma (Verner Morrison syndrome)Severe watery diarrhea (> 1L/die), hypokalemia, hypochlorhydriaRare7080
GlucagonomaNecrolytic migratory erythema, diabetes, weight loss, anemia, hypoaminoacidemia, venous thrombosisRare6080
SomatostatinomaDiarrhea, steatorrhea, weight loss, diabetes, cholelithiasisNot associated8480
CRH/ACTH-omaCushing's syndrome-90-
Table 5 Results of studies of molecularly targeted agents in patients with neuroendocrine tumours[54,55]
AgentResponse rate (%)PFS rate (%)/Duration
VEGF monoclonal antibody
Bevacizumab[56]1895 at 18 wk
mTOR inhibitor
RAD001 (everolimus)1371 at 24 wk
Temsirolimus[57]5.650 at 6 mo
Sunitinib10Median, 42 wk
VatalanibIn progress(time to progression)
SorafenibIn progress
PazopanibIn progress
PDGFR/Kit/Abl inhibitor
Imatinib[58]4Median, 5.9 mo
EGFR inhibitor
Gefitinib461 (carcinoids) and 31 (pancreatic tumor) at 6 mo
Bortezomib[59]0Median, 3 mo
(Time to treatment failure)