関: pancreatic endocrine tumor

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small room in which a monk or nun lives (同)cubicle
a device that delivers an electric current as the result of a chemical reaction (同)electric cell
a room where a prisoner is kept (同)jail cell, prison cell
(biology) the basic structural and functional unit of all organisms; they may exist as independent units of life (as in monads) or may form colonies or tissues as in higher plants and animals
any small compartment; "the cells of a honeycomb"
a small unit serving as part of or as the nucleus of a larger political movement (同)cadre
an abnormal new mass of tissue that serves no purpose (同)tumour, neoplasm
a small island (同)islet

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(刑務所の)『独房』;(修道院の)小さい独居室 / (ミツバチの)みつ房,巣穴 / 小さい部屋 / 『細胞』 / 電池 / 花粉室 / (共産党などの)細胞
《詩》島(island)
小島

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/11 11:33:39」(JST)

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Pancreatic neuroendocrine tumors (PanNETs, PETs, or PNETs), often referred to as "islet cell tumors",^[1]^[2] or "pancreatic endocrine tumors"^[3]^[4] are neuroendocrine neoplasms that arise from cells of the endocrine (hormonal) and nervous system within the pancreas.

PanNETs are a type of neuroendocrine tumor, representing about one third of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Many PanNETs are benign, while some are malignant. Aggressive PanNET tumors have traditionally been termed "islet cell carcinoma".

PanNETs are quite distinct from the usual form of pancreatic cancer, the majority of which are adenocarcinomas, which arises in the exocrine pancreas. Only 1 or 2% of clinically significant pancreas neoplasms are PanNETs.

Types

PanNETs are sometimes abbreviated as PETs or PNETs: such use should not to be confused with the primitive neuroectodermal tumor (PNET).

The majority of PanNETs are benign, while some are malignant. The World Health Organization (WHO) classification scheme places neuroendocrine tumors into three main categories, which emphasize the tumor grade rather than the anatomical origin.^[3] In practice, those tumors termed well or intermediately differentiated PanNETs in the WHO scheme are sometimes called "islet cell tumors." The high grade subtype, termed neuroendocrine cancer (NEC) in the WHO scheme, is synonymous with "islet cell carcinoma".

Signs and symptoms

Some PanNETs do not cause any symptoms, in which case they may be discovered incidentally on a CT scan performed for a different purpose.^[5]^:43–44 Symptoms such as abdominal or back pain or pressure, diarrhea, indigestion, or yellowing of the skin and whites of the eyes can arise from the effects of a larger PanNET tumor, either locally or at a metastasis.^[6]^{[medical citation needed]} About 40%^{[medical citation needed]} of PanNETS have symptoms related to excessive secretion of hormones or active polypeptides and are accordingly labeled as "functional"; the symptoms reflect the type of hormone secreted, as discussed below. Up to 60%^{[medical citation needed]} of PanNETs are nonsecretory or nonfunctional, in which there is no secretion, or the quantity or type of products, such as pancreatic polypeptide (PPoma), chromogranin A, and neurotensin, do not cause a clinical syndrome although blood levels may be elevated.^[7] In total, 85% of PanNETs have an elevated blood marker.^[2]

Functional tumors are often classified by the hormone most strongly secreted, for example:

gastrinoma: the excessive gastrin causes Zollinger–Ellison syndrome (ZES) with peptic ulcers and diarrhea
insulinoma:^[8] hypoglycemia occurs with concurrent elevations of insulin, proinsulin and C peptide^[9]
glucagonoma: the symptoms are not all due to glucagon elevations,^[9] and include a rash, sore mouth, altered bowel habits, venous thrombosis, and high blood glucose levels^[9]
VIPoma, producing excessive vasoactive intestinal peptide, which may cause profound chronic watery diarrhea and resultant dehydration, hypokalemia, and achlorhydria (WDHA or pancreatic cholera syndrome)
somatostatinoma: these rare tumors are associated with elevated blood glucose levels, achlorhydria, cholelithiasis, and diarrhea^[9]
less common types include ACTHoma, CRHoma, calcitoninoma, GHRHoma, GRFoma, and parathyroid hormone–related peptide tumor

In these various types of functional tumors, the frequency of malignancy and the survival prognosis have been estimated dissimilarly, but a pertinent accessible summary is available.^[10]

Diagnosis

Imaging

CT, MRI, EUS, SRS^[11]
Octreotide scaning

Biochemical evaluation

MEN1

Personal and family history should be evaluated for MEN1.

Staging

The 2010 WHO classification of tumors of the digestive system grades all the neuroendocrine tumors into three categories, based on their degree of cellular differentiation (from well-differentiated "NET G1" through to poorly-differentiated "NET G3"). The NCCN recommends use of the same AJCC-UICC staging system as pancreatic adenocarcinoma.^[5]^:52 Using this scheme, the stage by stage outcomes for PanNETs are dissimilar to pancreatic exocrine cancers.^[12] A different TNM system for PanNETs has been proposed by The European Neuroendocrine Tumor Society.^[13]

Pancreatic neuroendocrine tumor staging (AJCC)
Stage T1
Stage T2
Stage T3
Stage T4
Involvement of nearby lymph nodes – Stage N1
Metastasis – stage M1

Treatment

In general, treatment for PanNET encompasses the same array of options as other neuroendocrine tumors, as discussed in that main article. However, there are some specific differences, which are discussed here.^[5]

In functioning PanNETs, octreotide is usually recommended prior to biopsy^[5]^:21 or surgery^[5]^:45 but is generally avoided in insulinomas to avoid profound hypoglycemia.^[5]^:69

PanNETs in MEN1 are often multiple, and thus require different treatment and surveillance strategies.^[5]

Some PanNETs are more responsive to chemotherapy than are gastroenteric carcinoid tumors. Several agents have shown activity.^[9] In well differentiated PanNETs, chemotherapy is generally reserved for when there are no other treatment options. Combinations of several medicines have been used, such as doxorubicin with streptozocin and fluorouracil (5-FU)^[9]^[14] and capecitabine with temozolomide.^[14] Although marginally effective in well-differentiated PETs, cisplatin with etoposide has some activity in poorly differentiated neuroendocrine cancers (PDNECs),^[9] particularly if the PDNEC has an extremely high Ki-67 score of over 50%.^[5]^:30

Several targeted therapy agents have been approved in PanNETs by the FDA based on improved progression-free survival (PFS):

everolimus (Afinitor) is labeled for treatment of progressive neuroendocrine tumors of pancreatic origin in patients with unresectable, locally advanced or metastatic disease.^[15]^[16] The safety and effectiveness of everolimus in carcinoid tumors have not been established.^[15]^[16]
sunitinib (Sutent) is labeled for treatment of progressive, well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease.^[17]^[18] Sutent also has approval from the European Commission for the treatment of 'unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumors with disease progression in adults'.^[19] A phase III study of sunitinib treatment in well differentiated pNET that had worsened within the past 12 months (either advanced or metastatic disease) showed that sunitinib treatment improved progression-free survival (11.4 months vs. 5.5 months), overall survival, and the objective response rate (9.3% vs. 0.0%) when compared with placebo.^[20]

Genetics

DNA mutation analysis in well-differentiated pancreatic neuroendocrine tumors identified four important findings:^[21]^[22]

as expected, the genes mutated in NETs, MEN1, ATRX, DAXX, TSC2, PTEN and PIK3CA,^[21] are different from the mutated genes previously found in pancreatic adenocarcinoma.^[23]^[24]

one in six well-differentiated pancreatic NETs have mutations in mTOR pathway genes, such as TSC2, PTEN and PIK3CA.^[21] The sequencing discovery might allow selection of which NETs would benefit from mTOR inhibition such as with everolimus, but this awaits validation in a clinical trial.

mutations affecting a new cancer pathway involving ATRX and DAXX genes were found in about 40% of pancreatic NETs.^[21] The proteins encoded by ATRX and DAXX participate in chromatin remodeling of telomeres;^[25] these mutations are associated with a telomerase-independent maintenance mechanism termed ALT (alternative lengthening of telomeres) that results in abnormally long telomeric ends of chromosomes.^[25]

ATRX/DAXX and MEN1 mutations were associated with a better prognosis.^[21]

References

^ Burns WR, Edil BH (March 2012). "Neuroendocrine pancreatic tumors: guidelines for management and update". Current treatment options in oncology 13 (1): 24–34. doi:10.1007/s11864-011-0172-2. PMID 22198808.
^ ^a ^b Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment (PDQ) Health Professional Version. National Cancer Institute. March 7, 2014. [1]
^ ^a ^b The PanNET denomination is in line with current WHO guidelines. Historically, PanNETs have also been referred to by a variety of terms, and are still often called "islet cell tumors" or "pancreatic endocrine tumors". See: Klimstra DS, Modlin IR, Coppola D, et al. (August 2010). "The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems" (PDF). Pancreas 39 (6): 707–12. doi:10.1097/MPA.0b013e3181ec124e. PMID 20664470.
^ Oberg, K (2010). "Pancreatic endocrine tumors". Seminars in Oncology 37 (6): 594–618. doi:10.1053/j.seminoncol.2010.10.014. PMID 21167379.
^ ^a ^b ^c ^d ^e ^f ^g ^h "Neuroendocrine tumors, NCCN Guidelines Version 1.2015" (PDF). NCCN Guidelines. National Comprehensive Cancer Network, Inc. November 11, 2014. Retrieved December 25, 2014.
^ Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment (PDQ®) National Cancer Institute [2]
^ Jensen RT, Berna MJ, Bingham DB, Norton JA (2008). "Inherited pancreatic endocrine tumor syndromes: Advances in molecular pathogenesis, diagnosis, management, and controversies". Cancer 113 (7 Suppl): 1807–1843. doi:10.1002/cncr.23648. PMC 2574000. PMID 18798544.
^ Grant C (2005). "Insulinoma". Best Practice & Research Clinical Gastroenterology 19 (5): 783–798. doi:10.1016/j.bpg.2005.05.008. PMID 16253900.
^ ^a ^b ^c ^d ^e ^f ^g Benson AB, Myerson RJ, and Sasson AR. Pancreatic, neuroendocrine GI, and adrenal cancers. Cancer Management: A Multidisciplinary Approach 13th edition 2010. ISBN 978-0-615-41824-7 Text is available electronically (but may require free registration) at http://www.cancernetwork.com/cancer-management/pancreatic/article/10165/1802606
^ Ramage JK, Davies AH, Ardill J, et al. (Jun 2005). "Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours". Gut. 54. Suppl 4 (suppl_4): iv1–16. doi:10.1136/gut.2004.053314. PMC 1867801. PMID 15888809.
^ Ong, ES Neoplasms of the Endocrine Pancreas Workup - Imaging Studies
^ National Cancer Institute. Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment (PDQ®) Incidence and Mortality [3]
^ Öberg K, Knigge U, Kwekkeboom D, Perren A (October 2012). "Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up". Annals of Oncology: Official Journal of the European Society for Medical Oncology / ESMO. 23 Suppl 7: vii124–30. doi:10.1093/annonc/mds295. PMID 22997445. (Table 5 outlines the proposed TNM staging system for PanNETs.)
^ ^a ^b Tejani MA, Saif MW (2014). "Pancreatic neuroendocrine tumors: Does chemotherapy work?". JOP : Journal of the pancreas 15 (2): 132–4. doi:10.6092/1590-8577/2301 (inactive 2014-12-26). PMID 24618436. Missing or empty |title= (help)
^ ^a ^b Everolimus Approved for Pancreatic Neuroendocrine Tumors. The ASCO Post. May 15, 2011, Volume 2, Issue 8 http://ascopost.com/articles/may-15-2011/everolimus-approved-for-pancreatic-neuroendocrine-tumors/
^ ^a ^b http://www.pharma.us.novartis.com/product/pi/pdf/afinitor.pdf
^ National Cancer Institute. Cancer Drug Information. FDA Approval for Sunitinib Malate. Pancreatic Neuroendocrine Tumors http://www.cancer.gov/cancertopics/druginfo/fda-sunitinib-malate
^ http://labeling.pfizer.com/ShowLabeling.aspx?id=607
^ "Pfizer Scores New Approval for Sutent in Europe". 2 Dec 2010.
^ Raymond E, Dahan L, Raoul JL, et al. (2011). "Sunitinib malate for the treatment of pancreatic neuroendocrine tumors". N Engl J Med 364 (6): 501–13. doi:10.1056/NEJMoa1003825. PMID 21306237.
^ ^a ^b ^c ^d ^e Jiao, Y.; Shi, C.; Edil, B. H.; De Wilde, R. F.; Klimstra, D. S.; Maitra, A.; Schulick, R. D.; Tang, L. H.; Wolfgang, C. L.; Choti, M. A.; Velculescu, V. E.; Diaz Jr, L. A.; Vogelstein, B.; Kinzler, K. W.; Hruban, R. H.; Papadopoulos, N. (2011). "DAXX/ATRX, MEN1, and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine Tumors". Science 331 (6021): 1199–1203. doi:10.1126/science.1200609. PMID 21252315.
^ McKenna, L. R.; Edil, B. H. (2014). "Update on pancreatic neuroendocrine tumors". Gland surgery 3 (4): 258–275. doi:10.3978/j.issn.2227-684X.2014.06.03. PMID 25493258.
^ Jones, S.; Zhang, X.; Parsons, D. W.; Lin, J. C. -H.; Leary, R. J.; Angenendt, P.; Mankoo, P.; Carter, H.; Kamiyama, H.; Jimeno, A.; Hong, S. -M.; Fu, B.; Lin, M. -T.; Calhoun, E. S.; Kamiyama, M.; Walter, K.; Nikolskaya, T.; Nikolsky, Y.; Hartigan, J.; Smith, D. R.; Hidalgo, M.; Leach, S. D.; Klein, A. P.; Jaffee, E. M.; Goggins, M.; Maitra, A.; Iacobuzio-Donahue, C.; Eshleman, J. R.; Kern, S. E.; Hruban, R. H. (2008). "Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses". Science 321 (5897): 1801–1806. doi:10.1126/science.1164368. PMC 2848990. PMID 18772397.
^ Harada, T.; Chelala, C.; Crnogorac-Jurcevic, T.; Lemoine, N. R. (2009). "Genome-Wide Analysis of Pancreatic Cancer Using Microarray-Based Techniques". Pancreatology 9 (1–2): 13–24. doi:10.1159/000178871. PMID 19077451.
^ ^a ^b Heaphy CM, De Wilde RF, Jiao Y, et al. (2011). "Altered Telomeres in Tumors with ATRX and DAXX Mutations". Science 333 (6041): 425. doi:10.1126/science.1207313. PMID 21719641.

External links

Pancreatic neuroendocrine tumor at DMOZ

UpToDate Contents

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1. 膵神経内分泌腫瘍（膵島細胞腫瘍）の分類、疫学、臨床症状、局在、および病期分類 classification epidemiology clinical presentation localization and staging of pancreatic neuroendocrine tumors islet cell tumors
2. 転移性膵神経内分泌腫瘍および低分化胃腸膵管神経内分泌腫瘍：腫瘍増殖をコントローするための全身療法およびホルモン分泌過剰の症状 metastatic pancreatic neuroendocrine tumors and poorly differentiated gastroenteropancreatic neuroendocrine carcinomas systemic therapy options to control tumor growth and symptoms of hormone hypersecretion
3. VIP産生腫瘍症候群 the vipoma syndrome
4. ゾリンジャー - エリソン症候群（ガストリノーマ）の臨床症状および診断 clinical manifestations and diagnosis of zollinger ellison syndrome gastrinoma
5. インスリノーマ insulinoma

English Journal

Over-expression of insulin-response element binding protein-1 (IRE-BP1) in mouse pancreatic islets increases expression of RACK1 and TCTP: Beta cell markers of high glucose sensitivity.

Villafuerte BC1, Barati MT1, Rane MJ1, Isaacs S2, Li M2, Wilkey DW2, Merchant ML3.
Biochimica et biophysica acta.Biochim Biophys Acta.2017 Feb;1865(2):186-194. doi: 10.1016/j.bbapap.2016.10.015. Epub 2016 Nov 3.
BACKGROUND: A targeted analysis of the 50kDa C-terminal fragment of insulin-response element binding protein-1 (IRE-BP1) activation of target genes through the insulin receptor substrate receptor/PI-3 kinase/Akt pathway has been demonstrated for the insulin growth factor-1 receptor. The broader effe
PMID 27816562

Prkar1a gene knockout in the pancreas leads to neuroendocrine tumorigenesis.

Saloustros E1, Salpea P1, Starost M2, Liu S1, Faucz FR1, London E1, Szarek E1, Song WJ3, Hussain M3, Stratakis CA4.
Endocrine-related cancer.Endocr Relat Cancer.2017 Jan;24(1):31-40. Epub 2016 Nov 1.
Carney complex (CNC) is a rare disease associated with multiple neoplasias, including a predisposition to pancreatic tumors; it is caused most frequently by the inactivation of the PRKAR1A gene, a regulator of the cyclic AMP (cAMP)-dependent kinase (PKA). The method used was to create null alleles o
PMID 27803029

A new scaffold containing small intestinal submucosa and mesenchymal stem cells improves pancreatic islet function and survival in vitro and in vivo.

Wang D1, Ding X1, Xue W1, Zheng J1, Tian X1, Li Y1, Wang X1, Song H1, Liu H1, Luo X1.
International journal of molecular medicine.Int J Mol Med.2017 Jan;39(1):167-173. doi: 10.3892/ijmm.2016.2814. Epub 2016 Nov 29.
It is unknown whether a scaffold containing both small intestinal submucosa (SIS) and mesenchymal stem cells (MSCs) for transplantation may improve pancreatic islet function and survival. In this study, we examined the effects of a SIS-MSC scaffold on islet function and survival in vitro and in
PMID 27909715

Japanese Journal

非膵臓腫瘍に伴う低血糖症 (特集低血糖症の鑑別診断)

内分泌・糖尿病・代謝内科 = Endocrinology, diabetology & metabolism 41(3), 192-197, 2015-09
NAID 40020603842

Non-Islet Cell Tumor Hypoglycemia Is Caused by Big IGF-II in a Patient with a Carcinosarcoma of the Uterus

Internal Medicine 54(24), 3165-3169, 2015
NAID 130005114256

F344/DuCrlCrljラットの自然発生腫瘍

産業衛生学雑誌 57(3), 85-96, 2015
NAID 130005075466

Related Pictures

★リンクテーブル★

リンク元	「膵島細胞腫瘍」「島細胞腫瘍」「膵ラ島腫瘍」「nesidioblastoma」
拡張検索	「malignant islet cell tumor」
関連記事	「islet cell」「islet」「tumor」「cell」

「膵島細胞腫瘍」

Pancreatic neuroendocrine tumor
Classification and external resources
Specialty	Oncology
ICD-10	C25.4
eMedicine	med/

　　[★]

英: islet cell tumor, pancreatic endocrine tumor
同: 膵島細胞腫、膵島細胞腺腫、膵島腫瘍、膵小島腫瘍、島細胞腫瘍
関: 膵臓; ランゲルハンス島腫瘍、ランゲルハンス島細胞腫瘍; ガストリン産生腫瘍、グルカゴン産生腫瘍、ソマトスタチン産生腫瘍

[show details]

膵島腫瘍 : 約 12,800 件
膵島細胞腫瘍 : 約 107,000 件

多血性
造影CTの同脈相で強く濃染する
膵臓から発生する内分泌腫瘍。
ランゲルハンス島由来の細胞から由来するが、一部膵管上皮や腺房細胞の間に存在する細胞に由来するものがある

「島細胞腫瘍」

　　[★]

英: islet cell tumor
関: 膵島細胞腫瘍、膵ラ島腫瘍、膵島腫瘍

「膵ラ島腫瘍」

　　[★]

英: islet cell tumor
関: 膵島細胞腫瘍、島細胞腫瘍、膵島腫瘍

「nesidioblastoma」

　　[★]

膵ラ氏島細胞腺腫

関: islet cell adenoma、islet cell tumor

「malignant islet cell tumor」

　　[★]

膵島細胞悪性腫瘍

関: islet cell carcinoma

「islet cell」

　　[★]

島細胞

関: endocrine pancreas、islets of Langerhans、pancreatic islet

同: islet cell, regeneration of

「islet」

　　[★]

n.

島

adj.

島状の

関: insula、insulae

「tumor」

　　[★]

n.

腫瘍、腫瘤、腫脹

「cell」

　　[★] 細胞　　　　　　　

[Burns2012-1] Burns WR, Edil BH (March 2012). "Neuroendocrine pancreatic tumors: guidelines for management and update". Current treatment options in oncology 13 (1): 24–34. doi:10.1007/s11864-011-0172-2. PMID 22198808.

[PDQ-2] Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment (PDQ) Health Professional Version. National Cancer Institute. March 7, 2014. [1]

[Klimstra2010-3] The PanNET denomination is in line with current WHO guidelines. Historically, PanNETs have also been referred to by a variety of terms, and are still often called "islet cell tumors" or "pancreatic endocrine tumors". See: Klimstra DS, Modlin IR, Coppola D, et al. (August 2010). "The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems" (PDF). Pancreas 39 (6): 707–12. doi:10.1097/MPA.0b013e3181ec124e. PMID 20664470.

[4] Oberg, K (2010). "Pancreatic endocrine tumors". Seminars in Oncology 37 (6): 594–618. doi:10.1053/j.seminoncol.2010.10.014. PMID 21167379.

[NCCN_NET201501-5] ^ ^a ^b ^c ^d ^e ^f ^g ^h "Neuroendocrine tumors, NCCN Guidelines Version 1.2015" (PDF). NCCN Guidelines. National Comprehensive Cancer Network, Inc. November 11, 2014. Retrieved December 25, 2014.

[6] Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment (PDQ®) National Cancer Institute [2]

[Jensen2008-7] Jensen RT, Berna MJ, Bingham DB, Norton JA (2008). "Inherited pancreatic endocrine tumor syndromes: Advances in molecular pathogenesis, diagnosis, management, and controversies". Cancer 113 (7 Suppl): 1807–1843. doi:10.1002/cncr.23648. PMC 2574000. PMID 18798544.

[Grant2005-8] Grant C (2005). "Insulinoma". Best Practice & Research Clinical Gastroenterology 19 (5): 783–798. doi:10.1016/j.bpg.2005.05.008. PMID 16253900.

[Benson2010-9] ^ ^a ^b ^c ^d ^e ^f ^g Benson AB, Myerson RJ, and Sasson AR. Pancreatic, neuroendocrine GI, and adrenal cancers. Cancer Management: A Multidisciplinary Approach 13th edition 2010. ISBN 978-0-615-41824-7 Text is available electronically (but may require free registration) at http://www.cancernetwork.com/cancer-management/pancreatic/article/10165/1802606

[Ramage2005-10] Ramage JK, Davies AH, Ardill J, et al. (Jun 2005). "Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours". Gut. 54. Suppl 4 (suppl_4): iv1–16. doi:10.1136/gut.2004.053314. PMC 1867801. PMID 15888809.

[11] Ong, ES Neoplasms of the Endocrine Pancreas Workup - Imaging Studies

[NCI_FIG1-12] National Cancer Institute. Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment (PDQ®) Incidence and Mortality [3]

[Oberg-2012-13] Öberg K, Knigge U, Kwekkeboom D, Perren A (October 2012). "Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up". Annals of Oncology: Official Journal of the European Society for Medical Oncology / ESMO. 23 Suppl 7: vii124–30. doi:10.1093/annonc/mds295. PMID 22997445. (Table 5 outlines the proposed TNM staging system for PanNETs.)

[Tejani2014-14] Tejani MA, Saif MW (2014). "Pancreatic neuroendocrine tumors: Does chemotherapy work?". JOP : Journal of the pancreas 15 (2): 132–4. doi:10.6092/1590-8577/2301 (inactive 2014-12-26). PMID 24618436. Missing or empty |title= (help)

[ASCOPost20110515Evero-15] Everolimus Approved for Pancreatic Neuroendocrine Tumors. The ASCO Post. May 15, 2011, Volume 2, Issue 8 http://ascopost.com/articles/may-15-2011/everolimus-approved-for-pancreatic-neuroendocrine-tumors/

[Afinitor-PI-16] ttp://www.pharma.us.novartis.com/product/pi/pdf/afinitor.pdf

[NCIPET-17] National Cancer Institute. Cancer Drug Information. FDA Approval for Sunitinib Malate. Pancreatic Neuroendocrine Tumors http://www.cancer.gov/cancertopics/druginfo/fda-sunitinib-malate

[Sutent-PI-18] ttp://labeling.pfizer.com/ShowLabeling.aspx?id=607

[EU2010-19] "Pfizer Scores New Approval for Sutent in Europe". 2 Dec 2010.

[Raymond2011-20] Raymond E, Dahan L, Raoul JL, et al. (2011). "Sunitinib malate for the treatment of pancreatic neuroendocrine tumors". N Engl J Med 364 (6): 501–13. doi:10.1056/NEJMoa1003825. PMID 21306237.

[Jiao2011-21] Jiao, Y.; Shi, C.; Edil, B. H.; De Wilde, R. F.; Klimstra, D. S.; Maitra, A.; Schulick, R. D.; Tang, L. H.; Wolfgang, C. L.; Choti, M. A.; Velculescu, V. E.; Diaz Jr, L. A.; Vogelstein, B.; Kinzler, K. W.; Hruban, R. H.; Papadopoulos, N. (2011). "DAXX/ATRX, MEN1, and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine Tumors". Science 331 (6021): 1199–1203. doi:10.1126/science.1200609. PMID 21252315.

[McKenna2014-22] McKenna, L. R.; Edil, B. H. (2014). "Update on pancreatic neuroendocrine tumors". Gland surgery 3 (4): 258–275. doi:10.3978/j.issn.2227-684X.2014.06.03. PMID 25493258.

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islet cell tumor