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..

Grading of PNETs by the highest Ki-67 index in EUS-FNA specimens with adequate cellularity has a high concordance with grading of resected specimens, and can predict long term patient survival with high accuracy.

EUS-FNA for pancreatic solid lesions yielded a high accuracy and low complication rate. Both cytological and cell-block preparations and on-site cytopathological evaluation contributed to improve the accuracy. The diagnostic ability of EUS-FNA was less for smaller lesions, and repeated procedures may be needed if malignancy is suspected.

EUS-CDS is safe, feasible, and effective as an alternative to PTBD and EBD in cases of malignant distal biliary tract obstruction. Prospective randomized studies are needed to compare the safety and efficacy of various kinds of endoscopic devices used in EUS-CDS and to compare EUS-CDS with PTBD or EBD.

Pancreatic cysts are common and often pose a management dilemma, because some cysts are precancerous, whereas others have little risk of developing into invasive cancers. We used supervised machine learning techniques to develop a comprehensive test, CompCyst, to guide the management of patients with pancreatic cysts. The test is based on selected clinical features, imaging characteristics, and cyst fluid genetic and biochemical markers. Using data from 436 patients with pancreatic cysts, we trained CompCyst to classify patients as those who required surgery, those who should be routinely monitored, and those who did not require further surveillance. We then tested CompCyst in an independent cohort of 426 patients, with histopathology used as the gold standard. We found that clinical management informed by the CompCyst test was more accurate than the management dictated by conventional clinical and imaging criteria alone. Application of the CompCyst test would have spared surgery in more than half of the patients who underwent unnecessary resection of their cysts. CompCyst therefore has the potential to reduce the patient morbidity and economic costs associated with current standard-of-care pancreatic cyst management practices.