What is a Neuroendocrine Tumor?

The neuroendocrine system consists of highly specialized neuroendocrine cells which act as an interface or junction between the nervous system and the endocrine system. The endocrine system is made up of cells whose function is to produce and secrete hormones into the bloodstream. Hormones are biochemical messengers that help to regulate many different processes within the body. The nervous system is composed of specialized cells (neurons) that control the activities of all body parts.  A neuroendocrine cell is a cell which receives neuronal input (a signal from a nerve cell) and releases hormones in response to this signal.

A neuroendocrine tumor can develop anywhere there are neuroendocrine cells. The most common sites from which neuroendocrine tumors arise are the lungs, appendix, small intestine, rectum and pancreas (Yao, Hassan, Phan, Dagohoy, Leary, Mares, Abdalla, Fleming, Vauthey, Rashid, & Evans, 2008). Neuroendocrine tumors that arise in the pancreas are called pancreatic neuroendocrine tumors or islet cell tumors. When neuroendocrine tumors originate in other areas, they are often classified as carcinoid tumors.

Since neuroendocrine tumor cells are derived from neuroendocrine cells, many of these tumor cells can behave like cells they originated from and can secrete a variety of hormones. A functioning neuroendocrine tumor is one that secretes biologically active hormones causing a clinical syndrome. Non-functioning neuroendocrine tumors do not cause clinical syndromes.

Carcinoid tumors and pancreatic neuroendocrine tumors share similarities including often indolent behavior, ability to secrete biologically active hormones, and well-differentiated histology (Reidy, Tang & Saltz, 2009).

Pancreatic neuroendocrine tumors (PNET)  are a rare subgroup of tumors found in the pancreas and can be either functional or non-functional.  Their appearance in histology sections has little to contribute to their malignant potential since this traditionally depends on the extent of their spread. However, recent WHO   classification   classifies   PNET   into   well differentiated tumors,  well differentiated carcinomas and poorly differentiated carcinomas in an attempt to predict natural history from the pathology report.

They are usually sporadic but they may also appear among   other   features   of   genetic   syndromes   like multiple endocrine neoplasia type I or von Hippel-Lindau   disease.  Patients   usually   present   with syndromes   induced   by   hormones   secreted   from functional tumors,  or with mass effects from nonfunctional   tumors.  Functional   PNET   can   secrete biologically   active   peptides   like   insulin,  gastrin, glucagon,    somatostatin,    vasoactive     intestinal polypeptide (VIP), whereas non-functional tumors also express   and   secrete   peptides   like   neurotensin   or chromogranin A, which are not active.

Most of the PNET are already metastatic by the time they are diagnosed and liver is the most common site of metastasis.  Regional lymph node spread is also common.  PNET are non-functional in their majority and the absence of a distinct functional syndrome as well as their indolent course and subsequent delay in diagnosis is mainly responsible for the advanced stage at the time of diagnosis.  PNET have a 5-year survival   that   can   range   from   97%  in   benign insulinomas   to   as   low   as   30%  in   non-functional metastatic PNET.  In addition,  more recent data demonstrate that poorly differentiated PNET can have similar   prognosis   with   adenocarcinomas   of   the gastrointestinal tract.

Surgery   with   curative   intent   is   the   mainstay   of treatment for localized or loco-regional disease.

Surgery as well as other forms of local treatment like transarterial   chemoembolization   or   radiofrequency ablation can also improve prognosis in patients with liver metastases [2,  4,  5].  For the inoperable cases, cytotoxic therapy with compounds like streptozotocin, 5-fluorouracil   or   doxorubicin   can   achieve   modest outcome [6,  7,  8,  9].  Treatment with somatostatin analogues like octreotide has been proven to prolong progression-free survival in patients with metastatic neuroendocrine tumors of midgut origin.

This is a review of the recent advances in PNET as they were reported in four abstracts presented at the 2010   ASCO   Gastrointestinal   Cancers   Symposium.

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Oberg, K. E., Reubi, J. C., Kwekkeboom, D. J., Krenning, E. P. (2010) Role of somatostatins in gastroenteropancreatic neuroendocrine tumor development and therapy. Gastroenterology, 139(3), 742-753.

Ramage, J., Davies, A., Ardill, J., Caplin, M., Grossman, A., Hawkins, R., McNicol, A., Reed, N., Sutton, R., Thakker, R., Aylwin, S., Breen. D., Britton, K., Buchanan, K., Corie, P., Gillams, A., Lewington, V., McCance, D., Meeran, K., Watkinson, A., and UKNETwork for Neuroendocrine Tumors (2005).  Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut, 54(4), 1-16.

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