Neuroendocrine GEP-Tumors (GEP-NET)

PPoma / pancreatic Polypeptidoma
Definition	pancreatic NET originating from PP-cells with elevated secretion of pancreatic polypeptide (PP) - PP discovered in 1975
Incidence	incidence of "true" PPoma difficult to delineate, PPoma incidence estimated as 1 - 2 % of all pancreatic NET
	© www.gep-net.com / www.gep-net.de
Pathology - Pathophysiology	solitary, frequently large tumors ( <1 cm to > 10 cm) mostly in the pancreatic head, rarely extrapancreatic ( < 10% ) neoplastic PP-cells or PP-secretion frequently found in other NETs (Glucagonoma - 70 %, Vipoma - 42 %, Somatostatinom, Insulinoma - 37 %, Gastrinoma - 34 %, non-functioning NETs - 43 %, Carcinoid): PP may serve as a marker for the diagnosis of NETs Many assumed non-functioning GEP-NETs of the pancreas may represent clinically silent PPomas PP inhibits pancreatic and biliary secretion, CCK-antagonism, stimulation of PP via oral nutrient intake (proteins)
Clinical	no typical clinical syndrome mostly clinically silent PPomas abdominal pain, icterus due to tumor mass and hepatic rmetastases skin rash, watery diarrhea mediated through elevated PP-secretion ? oberserved: ulcer-diathesis, weight loss, diabetes mellitus
Diagnosis	preprandial PP-concentration > 300 pmol/l typical and diagnostic failure to inhibit PP by atropin, overstimulation with secretin iv. imaging techniques
Therapy	surgical resection (partial pancreatectomy, duodeno-pancreatectomy) - liver surgery (metastases) - chemoperfusion and -embolisation Somatostatin-Analogs, streptozotocin

Neurotensinoma / Ntoma
Definition	ectopic pancreatic NET with elevated secretion of neurotensin - first reported in 1981
Incidence	"pure" Ntomas very rare and often associated with gastrinomas, vipomas; > 50 Ntomas being described as GEP-NET
Pathology - Pathophysiology	Neurotensin: peptide of jejunal and ileal N-cells; stimulated by food intake; action: intestinal secretion, ileal contractions, duodenal relaxation & gastrooesophageal sphincter relaxation; inhibits interdigestive myoelectrical complex of the intestine, stimulates insulin mostly solitary, large tumors ( > 4 - 10 cm ) located in entire pancreas, extrapancreatic location extremely rare postulated symptoms: exaggerated intestinal secretion (diarrhea), reduced intestinal motility (obstipation), retarded stomach emptying; symptoms associated with ZES (gastrinoma) and VMS (vipoma); rarely hypoglycemia-syndrome (insulin) cosecreted peptides of Ntomas: gastrin, VIP, PP, calcitonin, bombesin, motilin
Clinical	clinical syndrome - variations 1. Zollinger-Ellison-Syndrome, Verner-Morrison-Syndrome 2. diarrhea with loss of electrolytes; obstipation possible symptoms (due to pharmacologic neurotensin actions): vasodilation, hypotension, edemas, cyanosis, tachycardia, hypoglycemia abdominal pain, icterus due to tumor mass and liver metastases
Diagnosis	many neurotensinomas remain undetected due to lacking assay analysis, which may be difficult (rapid degradation of a rather small peptide containing only 13 amino acids, AA) no established diagnostic tests available addressing stimulation or inhibition of NT - elevation of general markers of GEP-NET correct postsurgical diagnosis often only by means of specific immunohistochemical staining in neuroendocrine tumor cells imaging techniques
Therapy	surgical resection (partial pancreatectomy, e.g. duodeno-pancreatectomy) - liver surgery (metastases) - chemoperfusion and -embolisation Somatostatin analogs (?), streptozotocin (?)

Top