Pancreatic neuroendocrine tumors Pannets , PETs , or PNETs ), often referred to as "islet cell tumors", or "pancreatic endocrine tumor" is a neuroendocrine neoplasm arising from endocrine (hormonal) cells and the nervous system within the pancreas.
Pannet is a type of neuroendocrine tumor, representing about one-third of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Many PanNet are benign, while some are malignant. The aggressive PanNET tumor is traditionally called "islet cell carcinoma".
Pannets are quite different from the usual forms of pancreatic cancer, most of which are adenocarcinomas, which appear in the exocrine pancreas. Only 1 or 2% of clinically significant pancreatic neoplasms are Pannet.
Video Pancreatic neuroendocrine tumor
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The majority of PanNet is benign, while others are malignant. The World Health Organization (WHO) classification scheme places neuroendocrine tumors into three main categories, which emphasize tumor rates rather than the origin of anatomy. In practice, the tumors are called either differentiated or intermediate PanNets in the WHO scheme, sometimes called "islet cell tumors". A high level subtype, called neuroendocrine cancer (NEC) in the WHO scheme, is identical to "islet cell carcinoma".
Maps Pancreatic neuroendocrine tumor
Signs and symptoms
Some PanNet does not cause any symptoms, in which case they can be found by chance on CT scans performed for different purposes. Symptoms such as abdominal pain or back or pressure, diarrhea, indigestion, or yellowing of the skin and whites of the eyes may arise from the effects of larger PanNET tumors, either locally or on metastasis. Approximately 40% of PanNet has symptoms associated with excessive hormone secretion or active polypeptide and labeled as "functional"; symptoms reflect the type of hormone secreted, as discussed below. Up to 60% of Pannets are not nonsecretory or nonfunctional, where no secretion, or quantity or type of product, such as pancreatic polypeptide (PPoma), chromogranin A, and neurotensin, does not cause clinical syndrome even if the blood level may be elevated. In total, 85% of PanNet has a high blood marker.
Functional tumors are often grouped by the most secreted hormones, for example:
- gastrinoma: excessive gastrin causes Zollinger-Ellison syndrome (ZES) with peptic ulcer and diarrhea
- insulinoma: hypoglycemia occurs simultaneously with increased insulin, proinsulin, and peptide C
- glucagonoma: the symptoms are not all due to increased glucagon, and include rash, oral pain, changing bowel habits, venous thrombosis, and high blood glucose levels
- VIPoma, produces excessive vasoactive intestinal peptides, which can cause chronic pain w atery d iare and resultant dehydration, h ypokalemia, and a chlorhydria (WDHA or pancreas cholesterol syndrome)
- somatostatinoma: this rare tumor is associated with elevated blood glucose, achlorhydria, cholelithiasis, and diarrhea
- less common types include ACTHoma, CRHoma, calcitoninoma, GHRHoma, GRFoma, and parathyroid hormone-related peptide tumors
In various types of functional tumors, the frequency of malignancy and survival prognosis have been estimated not the same, but available relevant summaries.
Diagnosis
Because the symptoms are not specific, the diagnosis is often delayed.
Measurement of hormones including pancreatic polypeptide, gastrin, proinsulin, insulin, glucagon, and vasoactive venous peptide can determine whether the tumor causes hypersecretion.
CT and MRI can be used to determine the location and size of PNET.
Staging
The WHO 2010 classification of the gastrointestinal tumor assessed all neuroendocrine tumors into three categories, based on their cellular differentiation levels (from well-differentiated "NET G1" to "NET G3" poorly differentiated). The NCCN recommends the use of the same AJCC-UICC staging system as pancreatic adenocarcinoma. Using this scheme, the step-by-step results for PanNet are not the same as pancreatic exocrine cancer. The different TNM systems for PanNet have been proposed by The European Neuroendocrine Tumor Society.
- Pancreatic pancreatic neuroendocrine tumors (AJCC)
Treatment
In general, treatment for PanNet covers the same range of options as other neuroendocrine tumors, as discussed in the main article. However, there are some specific differences, which are discussed here.
In functioning PanNETs, ​​â € <â €
Pannet in multiple endocrine neoplasia type 1 is often multiple, and therefore requires different care and supervisory strategies.
Some PanNET are more responsive to chemotherapy than gastroenteric carcinoid tumors. Some agents have shown activity. In a well-differentiated PanNet, chemotherapy is generally provided when there are no other treatment options. Combinations of several drugs have been used, such as doxorubicin with streptozocin and fluorouracil (5-FU) and capecitabine with temozolomide. Although slightly effective in well-differentiated PET, cisplatin with etoposide has some activity in poorly differentiated neuroendocrine cancer (PDNECs), especially if PDNEC has a very high Ki-67 score above 50%.
Several targeted therapeutic agents have been approved at PanNet by the FDA based on the improvement of progression-free survival (PFS):
- everolimus (Afinitor) is labeled for the treatment of progressive neuroendocrine tumors from the pancreas in patients with localized or inoperable metastatic disease. The safety and effectiveness of everolymus in carcinoid tumors has not been established.
- sunitinib (Sutent) is labeled for the treatment of well-differentiated and differentiated differentiated pancreatic neuroendocrine tumors in patients with localized or inoperable metastatic disease. Sutent also received approval from the European Commission for the treatment of inoperable or metastatic pancreatic neuroendocrine tumors, well differentiated with the progression of the disease in adults. A phase III study of the treatment of sunitinib in well-differentiated pNET that has worsened in the last 12 months (either advanced or metastatic disease) suggests that sunitinib treatment increases progression-free survival (11.4 months vs. 5.5 months), overall survival, and goal response rate (9.3% vs. 0.0%) when compared with placebo.
Genetics
Pancreatic neuroendocrine tumors may appear in the context of some type of endocrine neoplasia 1 or Von Hippel-Lindau disease.
Analysis of somatic DNA mutations in well-differentiated pancreatic neuroendocrine tumors identifies four important findings:
- as expected, the mutated genes in NET, MEN1, ATRX, DAXX, TSC2, PTEN and PIK3CA, differ from mutated gene previously found in pancreatic adenocarcinoma.
- one of the six well-differentiated pancreatic webs has mutations in the mTOR path genes, such as TSC2, PTEN and PIK3CA. Sequence discovery might allow the selection of NETs that would benefit from mTOR inhibitors such as with everolymus, but this awaits validation in clinical trials.
- mutations that affect new cancer pathways involving the ATRX and DAXX genes are found in about 40% of the pancreatic NET. Proteins encoded by ATRX and DAXX participate in telomere chromatin remodeling; This mutation is associated with a telomerase-independent maintenance mechanism called ALT (an alternative telomere elongation) that produces a very long telomere end of the chromosome.
- ATRX/DAXX and MEN1 mutations are associated with a better prognosis.
References
External links
- Pancreatic neuroendocrine tumors in Curlie (based on DMOZ)
Source of the article : Wikipedia
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