Gastroenteropancreatic neuroendocrine neoplasms: A clinical snapshot

Table 5 Endoscopic and surgical management of gastroenteropancreatic-neuroendocrine neoplasms based on the location, grade, and size of the tumor[112,113]

Site of NENs	Type of NENs	Laboratory tests required	Abnormal results expected	Surveillance	Endoscopy (EMR/ESD)	Operation
Gastric NEN	Type 1 and type 2	CgA and gastrin	Raised CgA and gastrin	< 1 cm	1-2 cm: EMR or ESD	> 2 cm; local wedge resection
	Type 3 and type 4	CgA and gastrin	Raised CgA, normal gastrin	-	< 1 cm G1/2 type 3	> 1 cm; treat as adenocarcinoma
Duodenal NENs	1st part duodenum	CgA, gastrin, PP, 5-HIAA	Raised CgA, consider MEN1	-	< 1 cm G1 (EMR, not ESD; ESD increase perforation)	< 1 cm any other grade; > 1 cm any grade; gastrinoma and NEC any size
	Ampullary	CgA, somatostatin	Consider MEN1/NF1/VHL/TSC	-	< 2 cm G1: Papillectomy	> 2 cm or < 2 cm with G2/3: Surgery
Jejunoileal NENs	-	CgA, 5-HIAA, NKA	Raised CgA, 5-HIAA and NKA	-	-	Preoperative SSAs, look for CaHD, peroperative palpation-multifocal
Appendiceal NENs	-	CgA, 5-HIAA, NKA, PP	Not raised unless metastatic	-	-	< 2 cm: Appendectomy; > 2 cm: Right hemicolectomy
Colonic NENs	-	CgA, 5-HIAA, NKA, PP	Raised CgA, 5-HIAA and NKA	-	< 1 cm for G1, lack of submucosa infiltration	< 1 cm for G2/G3, muscle infiltrate or angioinvasion; > 1 cm any grade: Treat as adenocarcinoma with segmental colectomy and wide regional lymphadenectomy
Rectal NENs	-	CgA, PP, enteroglucagon, β-hCG	Raised CgA, PP, β-hCG and enteroglucagon	-	< 1 cm G1/2 (EMR/ESD)	1-2 cm G1/2, no nodal metastasis: Transanal resection; > 2 cm G1/2 with nodal spread, any size G3: Treat as adenocarcinoma
Pancreatic NENs	Functional pNEN, Non-functional pNEN, pNEN with MEN1 and inherited conditions	CgA, insulin, gastrin, VIP, glucagon, somatostatin, glucose, calcium, PTH, PP, prolactin, MEN1 genetics	Raised CgA: Metastatic NENs Raised hormones: F-pNENs Raised calcium, prolactin, PTH: Consider MEN1	Sporadic or MEN1 related NF-pNENs asymptomatic and < 2 cm; MEN1 related ZES < 2 cm	Sporadic or MEN1 related asymptomatic NF-pNEN and < 2 cm; insulinoma (pNENs with very low cancer risk)	NF-pNENs symptomatic or ≥ 2 cm; functional pNEN of any size except insulinoma. Open or robot assisted surgery. Robot assisted surgery: For precise reconstruction

NENs: Neuroendocrine neoplasms; pNENs: Pancreatic NENs; F-pNENs: Functional pNENs; NF-pNENs: Non-functional pNENs; CgA: Chromogranin A; 5-HIAA: 5-hydroxy indole acetic acid; NKA: Neurokinin A; PTH: Parathyroid hormone; PP: Pancreatic polypeptide; VIP: Vasoactive intestinal peptide; hCG: Human chorionic gonadotrophin; MEN1: Multiple endocrine neoplasia 1; NF1: Type 1 neurofibromatosis; VHL: Von Hippel-Lindau; TSC: Tuberous sclerosis; ZES: Zollinger Ellison syndrome; NEC: Neuroendocrine carcinoma; SSAs: Somatostatin analogues; CaHD: Carcinoid heart disease; EMR: Endoscopic mucosal resection; ESD: Endoscopic submucosal dissection; G1: Grade 1; G2: Grade 2; G3: Grade 3.