Patients with pancreatic neuroendocrine neoplasm grade-3 (PanNEN-G3) show variable responses to platinum-based chemotherapy. Recent studies indicated that PanNEN-G3 includes well-differentiated neuroendocrine tumor with G3 (NET-G3). Here, we examined the clinicopathologic and molecular features of PanNEN-G3 and assessed the responsiveness to chemotherapy and survival. A total of 100 patients with PanNEN-G3 were collected from 31 institutions, and after central review characteristics of each histologic subtype [NET-G3 vs. pancreatic neuroendocrine carcinoma (NEC-G3)] were analyzed, including clinical, radiological, and molecular features. Factors that correlate with response to chemotherapy and survival were assessed. Seventy patients analyzed included 21 NETs-G3 (30%) and 49 NECs-G3 (70%). NET-G3 showed lower Ki67-labeling index (LI; median 28.5%), no abnormal Rb expression (0%), and no mutated (0%), whereas NEC-G3 showed higher Ki67-LI (median 80.0%), Rb loss (54.5%), and mutations (48.7%). Chemotherapy response rate (RR), platinum-based chemotherapy RR, and prognosis differed significantly between NET-G3 and NEC-G3. Chemotherapeutic outcomes were worse in NET-G3 ( < 0.001). When we stratified PanNEN-G3 with Rb and , PanNENs-G3 with Rb loss and those with mutated showed significantly higher RRs to platinum-based chemotherapy than those without (Rb loss, 80% vs. normal Rb, 24%, = 0.006; mutated, 77% versus wild type, 23%, = 0.023). Rb was a predictive marker of response to platinum-based chemotherapy even in NEC-G3 ( = 0.035). NET-G3 and NEC-G3 showed distinct clinicopathologic characteristics. Notably, NET-G3 does not respond to platinum-based chemotherapy. Rb and are promising predictors of response to platinum-based chemotherapy for PanNEN-G3, and Rb for NEC-G3..

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BackgroundEndoscopic ultrasound-guided fine needle aspiration (EUS-FNA) provides high diagnostic accuracy with a low incidence of procedural complications. However, it occasionally causes serious complications, and factors that increase the susceptibility to such adverse events remain unknown.AimsWe aimed to examine post-procedural events and determine risk factors associated with EUS-FNA of pancreatic solid lesions.MethodsThis single-center retrospective study included 316 consecutive patients with pancreatic solid lesions who underwent 327 EUS-FNA procedures from April 2003 to September 2011. We registered all patients undergoing EUS-FNA in the database and retrospectively ascertained the presence/absence of post-procedural adverse events.ResultsThe incidence of post-procedural adverse events, including moderate to mild pancreatitis, mild abdominal pain, and mild bleeding, was 3.4 %. Univariate analysis showed that the incidence of post-procedural events was significantly increased in patients with tumors less than or equal to 20 mm in diameter (P < 0.001), those with pancreatic neuroendocrine tumors (PNET) (P = 0.012), and patients who had intervening normal pancreas for accessing the lesion (P = 0.048). Multivariate analysis identified tumors measuring less than or equal to 20 mm in diameter (OR 18.48; 95 % CI 3.55–96.17) and case of PNETs (OR 36.50; 95 % CI 1.73–771.83) were an independent risk factors.ConclusionsEUS-FNA of pancreatic solid lesions is a safe procedure. However, pancreatic lesions with small diameters and pancreatic neuroendocrine tumors are important factors associated with adverse events after EUS-FNA.

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