The NANETS Consensus Guideline for the Diagnosis and Management of Neuroendocrine Tumors

Abstract

Well-differentiated neuroendocrine tumors (NETs) of the jejunum, ileum, and appendix are also collectively known as midgut carcinoids. Similar to NETs in general, the diagnosed incidence of the midgut NETs is on the rise. Their presenting symptoms vary depending on stage and primary site. Local-regional NETs often present with vague and nonspecific symptoms. Classic carcinoid syndrome is more likely to appear in patients with advanced disease. Local-regional NETs of the small bowel should be resected whenever possible. With the exception of small well-differentiated NETs of the appendix, NETs of the midgut have substantial risk of relapse after resection and need to be followed for at least 7 years.Metastatic/advanced NETs of the midgut are incurable. Optimal management requires a multidisciplinary approach. Somatostatin analogs are effective in the management of carcinoid syndrome. Octreotide long-acting release has also recently been shown to delay disease progression. Liver-directed therapy and surgical debulking can improve quality of life in selected patients. Pivotal phase 3 studies with bevacizumab targeting vascular endothelial growth factor and everolimus targeting mTOR (mammalian target of rapamycin) are ongoing and may lead to improved outcome. Further studies of novel approaches such as peptide receptor radiotherapy are also warranted.

Small bowel neuroendocrine tumors: From pathophysiology to clinical approach

“…It consists of a polypeptide widely expressed in secretory granules of neuroendocrine cells. Plasma CgA is elevated in 60%100% of patients with NET, either functioning or nonfunctioning, with a sensitivity and specificity for detecting NET of 70% to 100% [29] . However, CgA levels are influenced by the assay used [30] and are highly influenced by several common conditions, and false elevation of this marker has been reported in patients using proton pump inhibitors, with renal or liver failure and even in chronic gastritis [31] .…”

“…Currently, chromogranin A (CgA) is the most important of these markers, and current guidelines recommend measure ment of serum CgA at diagnosis [5,6,29] . It consists of a polypeptide widely expressed in secretory granules of neuroendocrine cells.…”

“…However, CgA levels are influenced by the assay used [30] and are highly influenced by several common conditions, and false elevation of this marker has been reported in patients using proton pump inhibitors, with renal or liver failure and even in chronic gastritis [31] . Other proposed markers are plasma neuronspecific enolase, urinary 5HIAA (as a marker of carcinoid syndrome) and a variety of other secreted amines such as chromogranin B and C, substance P, neurotensin, among others [29] .…”

“…Jejunal and ileal NETs have a greater propensity to metastasize and are more frequently multiple lesions therefore, even in small tumors, surgery should involve search for additional tumors by inspection and palp ation [29] as well as wide lymphadenectomy [5] . In patients with liver metastases curative surgery should still be attempted, and intraoperative ultrasonography should be performed for detection of all liver metastases [5] .…”

“…Concerning treatment, clinical societies state that curative surgery should be aimed for in patients with duo denal, jejunal and ileal NETs whenever possible [5,6,29,38] . For small (≤ 1 cm) duodenal NETs local endoscopic resection is an option but larger duodenal NETs (≥ 2 cm) or the presence of lymph node metastases should be treated surgically [6] .…”