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©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
Published online Sep 21, 2008. doi: 10.3748/wjg.14.5377
Table 1 WHO classification[12]
Site | Well differentiated endocrine tumor | Well-differentiated endocrine carcinoma | Poorly-differentiated endocrine carcinoma | |
BB | UB | |||
Pancreas | < 2 cm | ≥ 2 cm | Local invasion | Small cells |
< 2 mitoses1 | > 2 mitoses | 2-10 mitoses | > 10 mitoses | |
< 2% Ki-67 | > 2% Ki-67 | > 5% Ki-67 | > 15% Ki-67 | |
No vascular invasion | Vascular invasion | Vascular invasion ± metastases | Vascular/perineural invasion | |
Stomach | Mucosa/Submucosa | Mucosa/Submucosa | Invasion of muscularis propria ± metastases | Small cells |
≤ 1 cm | > 1 cm | |||
No vascular invasion | Vascular invasion | |||
Duodenum/ | Mucosa/Submucosa | Mucosa/Submucosa | Invasion of muscularis propria ± metastases | Small cells |
Jejunum | ≤ 1 cm | > 1 cm | ||
No vascular invasion | Vascular invasion | |||
Ileum/ | Mucosa/Submucosa | Mucosa/Submucosa | Invasion of muscularis propria ± metastases | Small cells |
Colon/ | ≤ 1 cm (ileum) | > 1 cm (ileum) | ||
Rectum | ≤ 2 cm (colon) | > 2 cm (colon) | ||
No vascular invasion | Vascular invasion | |||
Appendix | ≤ 2 cm | > 2 cm | Extensive invasion of mesoappendix ± metastases | Small cells |
No vascular invasion | Vascular invasion |
Pancreatic NETs | Foregut and midgut gastrointestinal carcinoids | |||||
T-primary tumor | ||||||
Tx | Primary tumor cannot be assessed | Primary tumor cannot be assessed | ||||
T0 | No evidence of primary tumor | No evidence of primary tumor | ||||
T1 | Tumor limited to the pancreas and size < 2 cm | Tumor invades mucosa or submucosa and size ≤ 1 cm | ||||
T2 | Tumor limited to the pancreas and size 2-4 cm | Tumor invades muscularis propria and size > 1 cm | ||||
T3 | Tumor limited to the pancreas and size > 4 cm or invading duodenum or bile duct | Tumor invades subserosa | ||||
T4 | Tumor 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 tumors | For any T, add (m) for multiple tumors | |||||
N-regional lymph nodes | ||||||
Nx | Regional lymph nodes cannot be assessed | Regional lymph nodes cannot be assessed | ||||
N0 | No regional lymph node metastases | No regional lymph node metastases | ||||
N1 | Regional lymph node metastases | Regional lymph node metastases | ||||
M- distant metastases | ||||||
Mx | Distant metastases cannot be assessed | Distant metastases cannot be assessed | ||||
M0 | No distant metastases | No distant metastases | ||||
M1 | Distant metastases | Distant metastases | ||||
Disease stage | ||||||
I | T1 | N0 | M0 | T1 | N0 | M0 |
IIa | T2 | N0 | M0 | T2 | N0 | M0 |
IIb | T3 | N0 | M0 | T3 | N0 | M0 |
IIIa | T4 | N0 | M0 | T4 | N0 | M0 |
IIIb | Any T | N1 | M0 | Any T | N1 | M0 |
IV | Any T | Any N | M1 | Any T | Any N | M1 |
Table 3 Carcinoid syndrome
Clinical features | Incidence (%) | Characteristics | Mediators |
Flushing | 90 | Foregut tumors: prolonged fit, red-purple, localized to face and trunk. Midgut tumors: quick fit, pink-red. | Serotonin, histamine, P substance, prostaglandins |
Diarrhea | 70 | Secretory | Serotonin, histamine, VIP, prostaglandins, gastrin |
Abdominal pain | 40 | Long lasting | Obstruction, hepatomegaly, intestinal ischemia, fibrosis |
Profuse sweating | 15 | Serotonin, histamine | |
Telangiectasias | 25 | Face | Unknown cause |
Heart disease | 30 (right) | Valvulopathies (tricuspid valve, pulmonary valve). Right heart failure. Dyspnea | P substance, serotonin |
10 (left) | |||
Pellagra | 5 | Dermatitis | Deficit of niacin |
Table 4 Clinical features of the main endocrine pancreatic tumors
Tumor (syndrome) | Clinical features and diagnostic tests | MEN-1 (%) | Metastases (%) | SnSRS (%) |
Insulinoma | Spontaneous or fasting hypoglycemia (Whipple's triad) | 8-10 | 10 | 50 |
Positive fasting test (hypoglycemia with hyperinsulinism) | ||||
Gastrinoma (Zollinger-Ellison syndrome) | Peptic ulcers, diarrhea, GERD, BAO > 15 mEq/h | 30 | 60 | 80 |
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, hypochlorhydria | Rare | 70 | 80 |
Glucagonoma | Necrolytic migratory erythema, diabetes, weight loss, anemia, hypoaminoacidemia, venous thrombosis | Rare | 60 | 80 |
Somatostatinoma | Diarrhea, steatorrhea, weight loss, diabetes, cholelithiasis | Not associated | 84 | 80 |
CRH/ACTH-oma | Cushing's syndrome | - | 90 | - |
GHRH-oma | Acromegaly | - | - | - |
Agent | Response rate (%) | PFS rate (%)/Duration |
VEGF monoclonal antibody | ||
Bevacizumab[56] | 18 | 95 at 18 wk |
mTOR inhibitor | ||
RAD001 (everolimus) | 13 | 71 at 24 wk |
Temsirolimus[57] | 5.6 | 50 at 6 mo |
VEGF TKI | ||
Sunitinib | 10 | Median, 42 wk |
Vatalanib | In progress | (time to progression) |
Sorafenib | In progress | |
Pazopanib | In progress | |
PDGFR/Kit/Abl inhibitor | ||
Imatinib[58] | 4 | Median, 5.9 mo |
EGFR inhibitor | ||
Gefitinib | 4 | 61 (carcinoids) and 31 (pancreatic tumor) at 6 mo |
Other | ||
Bortezomib[59] | 0 | Median, 3 mo |
(Time to treatment failure) |
- Citation: Massironi S, Sciola V, Peracchi M, Ciafardini C, Spampatti MP, Conte D. Neuroendocrine tumors of the gastro-entero-pancreatic system. World J Gastroenterol 2008; 14(35): 5377-5384
- URL: https://www.wjgnet.com/1007-9327/full/v14/i35/5377.htm
- DOI: https://dx.doi.org/10.3748/wjg.14.5377