Treatment In the past, treatment options

for PETs have been limited, with hormonal treatment with octreotide (somatostatin analogues) as the primary therapeutic approach. Some PETs possess especially strong hormone receptors, such as somatostatin receptors and uptake hormones strongly (5). This avidity can assist in diagnosis and may make some tumors vulnerable to hormone targeted therapies. Although the optimal clinical management of PNETs involves a multidisciplinary approach, surgery remains the only curative treatment for early-stage disease. The surgical treatment continues to evolve for PETs, Inhibitors,research,lifescience,medical but the best outcome occurs in those treated with total tumor resection. Surgery may also have a role in patients with advanced-stage disease, including those with hepatic metastases (25). Alternative therapeutic approaches Inhibitors,research,lifescience,medical applied to PETs, including chemotherapy, radiofrequency ablation, transarterial chemoembolization, biotherapy, polypeptide radionuclide receptor therapy, antiangiogenic therapy, Inhibitors,research,lifescience,medical and selective internal radiotherapy (7). Chemotherapeutic agents have been used with limited efficacy (less effective

in well-differentiated tumors). Several agents have shown activity and combining several thearpies, particularly doxorubicin with streptozocin, is often more effective (26). Although marginally effective in well-differentiated PETs, cisplatin with etoposide is active in poorly-differentiated neuroendocrine Inhibitors,research,lifescience,medical cancers (5,26). Targeted therapy has a clear role as these tumors do overexpress receptors for EGF, PDGF, IGF-1, and VEGF. Recent studies demonstrate PI3K/Akt/mTOR pathway is involved in the pathogenesis of PETs (8,9). Based on the phase III clinical trials data, mTOR inhibitor

(Everolimus) significantly improved progression-free survival among patients with progressive advanced pancreatic neuroendocrine tumors as compared with placebo (9). This targeted chemotherapy agents have been approved by Inhibitors,research,lifescience,medical FDA in patients with progressive unresectable, locally advanced or metastatic pancreatic neuroendocrine tumors. The combination of an mTOR inhibitor and a VEGF Thalidomide inhibitor has also showed promising results (8). Conclusions In summary, pancreatic neuroendocrine tumors are generally indolent neoplasms, even though the majority do present at an advanced stage. Once PETs is suspected based on the histologic features, immunohistochemistry plays a critical role to confirm the diagnosis. The 2010 WHO classification of tumors of the digestive buy Pifithrin-�� system introduces grading and staging tools for pancreatic neuroendocrine neoplasms. A carcinoid is now defined as a grade 1 or 2 neuroendocrine tumor and grade 3, small-cell or large-cell carcinomas are defined as neuroendocrine carcinomas.