Pancreatic neuroendocrine carcinoma G3 may be heterogeneous and could be classified into two distinct groups.

BACKGROUND/OBJECTIVES: Pancreatic neuroendocrine carcinoma (PanNEC)-G3 often presents along with genetic abnormalities such as KRAS, RB1, and TP53 mutations. However, the association between these genetic findings and response to chemotherapy and prognosis has not been clarified. This study aimed to clarify the clinicopathological features of PanNEC-G3. METHODS: We performed a subgroup analysis of the Japanese PanNEN-G3 study (multicenter, retrospective study), which revealed that Rb loss and KRAS mutation were predictors of the response to platinum-based regimen in PanNEN-G3. We re-classified WHO grades of PanNENs using the 2017 WHO classification and then analyzed the clinicopathological features and prognostic factors in 49 patients with PanNEC-G3. RESULTS: The rates of Rb loss and KRAS mutation in PanNEC-G3 were 54.5% and 48.7%, respectively. Patients with Rb loss and/or KRAS mutation showed a higher response rate to first-line platinum-based regimen than those without Rb loss or KRAS mutation (object response rate 70.0% vs 33.3%, odds ratio 9.22; 95% CI 1.26-67.3, P = 0.029), but tended to have shorter overall survival rates than those without Rb loss or KRAS mutation (median 239 vs 473 days, hazard ratio 2.11; 95% CI 0.92-4.86, P = 0.077). CONCLUSIONS: Patients with PanNEC-G3 have varied clinical outcomes for platinum-based regimen. When grouped based on Rb loss and KRAS mutation, there seemed to be two groups with distinct prognoses and responses to the platinum-based regimen. PanNEC-G3 could, therefore, be classified into two distinct groups based on immunohistochemical and genetic findings.

Surgery for Pancreatic Neuroendocrine Tumor G3 and Carcinoma G3 Should be Considered Separately.

BACKGROUND: The role of surgery in pancreatic neuroendocrine neoplasm grade 3 (pNEN-G3) treatment remains unclear. We aimed to clarify the role of surgery for pNEN-G3, which has recently been reclassified as pancreatic neuroendocrine tumor-G3 (pNET-G3) and pancreatic neuroendocrine carcinoma-G3 (pNEC-G3), with and without metastases, respectively. METHODS: We analyzed a subgroup of patients from the Japanese pancreatic NEC study, a Japanese multicenter case-series study of pNEN-G3. Pathologists subclassified 67 patients as having pNET-G3 or pNEC-G3 based on morphological features. We compared the overall survival (OS) rates among patients who were grouped according to whether they had undergone tumor-targeted surgery for tumors without (SwoM) or with (SwM) metastases, or non-surgical procedures (NS). RESULTS: Data from 21 patients with pNET-G3 (SwoM, n = 6; SwM, n = 5; NS, n = 10) and 46 patients with pNEC-G3 (SwoM, n = 8; SwM, n = 5; NS, n = 33) were analyzed. OS of patients with pNET-G3 was significantly longer after SwoM and SwM than with NS (p = 0.018 and p = 0.022). In contrast, OS did not significantly differ between either SwoM or SwM and NS (p = 0.093 and p = 0.489) among patients with pNEC-G3. CONCLUSION: The role of surgery should be considered separately for pNET-G3 and pNEC-G3. Although SwoM and SwM can be considered for pNET-G3, caution is advised before considering SwM and SwoM for pNEC-G3.

Impact of retroflexion in the right colon after repeated forward-view examinations.

BACKGROUND AND AIM: Right colon polyps can especially be overlooked when they are located on the backs of haustral folds. Previous studies have reported that repeated forward-view examinations in the right colon were effective in reducing adenoma miss rates. The aim of this study was to clarify the impact of retroflexion in the right colon after repeated forward-view examinations. METHODS: This multicenter, prospective, observational study was conducted at three institutions in Kumamoto, Japan, between February 2014 and December 2015. Subjects who were over 40 years old and scheduled for colonoscopy were recruited. For the forward view, after cecal intubation, the colonoscope was withdrawn to the hepatic flexure. The colonoscope was sequentially reinserted to the cecum and then withdrawn to the hepatic flexure. For the retroflexion view (RV), the colonoscope was reinserted to the cecum, retroflexed, and then withdrawn to the hepatic flexure. All polyps were resected at the time of detection. The primary outcome of this study was the adenoma miss rate for the repeated forward-view examinations. RESULTS: Of the 777 enrolled participants, retroflexion was successful in 730 (94.0%). The repeated forward-view withdrawal technique detected 291 adenomas, while the third withdrawal in the RV detected 53. The adenoma miss rate for the repeated forward-view withdrawal was 15.4%. No severe adverse events occurred during retroflexion. CONCLUSION: Because adenomas located on potential blind spots can be missed when only using forward-view examinations, retroflexion in the right colon after repeated forward-view examinations might improve colonoscopy detection rates.

Rb Loss and KRAS Mutation Are Predictors of the Response to Platinum-Based Chemotherapy in Pancreatic Neuroendocrine Neoplasm with Grade 3: A Japanese Multicenter Pancreatic NEN-G3 Study.

Purpose: 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.Experimental Design: 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.Results: 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 KRAS (0%), whereas NEC-G3 showed higher Ki67-LI (median 80.0%), Rb loss (54.5%), and KRAS 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 (P < 0.001). When we stratified PanNEN-G3 with Rb and KRAS, PanNENs-G3 with Rb loss and those with mutated KRAS showed significantly higher RRs to platinum-based chemotherapy than those without (Rb loss, 80% vs. normal Rb, 24%, P = 0.006; mutated KRAS, 77% versus wild type, 23%, P = 0.023). Rb was a predictive marker of response to platinum-based chemotherapy even in NEC-G3 (P = 0.035).Conclusions: NET-G3 and NEC-G3 showed distinct clinicopathologic characteristics. Notably, NET-G3 does not respond to platinum-based chemotherapy. Rb and KRAS are promising predictors of response to platinum-based chemotherapy for PanNEN-G3, and Rb for NEC-G3. Clin Cancer Res; 23(16); 4625-32. ©2017 AACR.

Prospective, randomized, comparative study of delineation capability of radial scanning and curved linear array endoscopic ultrasound for the pancreaticobiliary region.

BACKGROUND AND STUDY AIMS: There are two types of endoscopic ultrasound (EUS) endoscope, the radial scanning (RS) and the curved linear array (CL). The type of EUS endoscope used at a first intent depends on local expertise, local habits and sometimes on how the examination is reimbursed. In Japan, RS is mainly used for observation, whereas CL is primarily used for histopathological diagnosis and treatment. We compared the imaging capabilities of RS and CL in evaluating the pancreaticobiliary region, a study which has not been performed previously. PATIENTS AND METHODS: This prospective and randomized trial included 200 patients undergoing endoscopic ultrasonography of the pancreaticobiliary region by RS (n = 99) or CL (n = 101). The primary end point was the basal imaging capability of each technique. Eleven pancreaticobiliary areas were assessed and scored (range, 0 - 2). Endoscopists evaluated each criterion, and a transcriber recorded the decisions in real time. RESULTS: The mean imaging scores in the RS and CL groups were 18.39 and 19.62, respectively (significantly higher in CL, 95 %CI: 0.82 - 1.64). Although no significant difference in imaging capability for the pancreatic head, body, or tail was observed between CL and RS, the imaging capability of CL for the pancreatic head - body transition region was superior to that of RS. Although no significant difference in imaging capability for the middle and inferior bile duct or the cystic duct was observed between CL and RS, the imaging capability of RS for the major duodenal papilla and gallbladder was superior to that of CL. For the area from the hepatic portal region to the superior bile duct, the imaging capability of CL was superior. In the delineation of the branch area of the celiac and superior mesenteric arteries, CL was also superior to RS. CONCLUSIONS: The non-inferiority of the overall imaging capability of CL to that of RS was demonstrated. CL was superior in the delineation of the pancreatic head - body transition region, the area from the hepatic portal region to the superior bile duct, and the vascular bifurcation, whereas RS was superior in the delineation of the major duodenal papilla and gallbladder. Thus, for detailed evaluations of specific areas, the choice of scope should probably be considered.

Large balloon dilation for the treatment of recurrent bile duct stones prevents short-term recurrence in patients with previous endoscopic sphincterotomy.

BACKGROUND/PURPOSE: Our previous study revealed the efficacy and safety of the large balloon dilation (LBD) technique. However, there is insufficient objective data about the recurrence rate. The aim of this study was to compare the recurrence rate of common bile duct (CBD) stones between patients treated with and without LBD. METHODS: Patients with recurrent CBD stones treated between April 2006 and August 2010, and who had a history of endoscopic sphincterotomy (ES), were enrolled. Patients were excluded if they had a CBD diameter of less than 10 mm or if the diameter of their largest CBD stone was <10 mm. RESULTS: A total of 62 consecutive patients were investigated. From April 2006 to November 2007, 32 patients were treated without LBD (non-LBD group; historical control). From December 2007 to August 2010, 30 patients underwent LBD (LBD group). The median follow-up times in the LBD and non-LBD groups were 517 and 1034 days (p < 0.001), respectively. Kaplan-Meier analysis revealed a significantly lower incidence of recurrent CBD stones in the LBD group than in the non-LBD group (p = 0.048). CONCLUSIONS: LBD reduces the short-term recurrence of CBD stones in patients with previous ES.

Safety and long-term outcomes of endoscopic papillary balloon dilation in children with bile duct stones.

BACKGROUND: Although experience with diagnostic and therapeutic ERCP in children is growing, little is known about the safety and technical outcomes of endoscopic papillary balloon dilation (EPBD) in pediatric patients with bile duct stones (BDSs). OBJECTIVE: To assess the safety and long-term outcomes of EPBD in pediatric patients with BDSs. DESIGN: Case study. SETTING: Tertiary referral center. PATIENTS AND INTERVENTIONS: This study involved 5 children who had BDSs combined with gallstones who underwent EPBD. MAIN OUTCOME MEASUREMENTS: Successful EPBD, successful stone removal, procedure-related complications, and long-term outcomes. RESULTS: ERCP was successful in all cases, with cannulation and subsequent EPBD. Stone removal was performed in 1 session in all patients. No EPBD-related complications were observed in any patient. After EPBD, 1 patient subsequently underwent laparoscopic cholecystectomy for gallstones. The remaining 4 were followed without surgery. In 2 patients, gallstones were spontaneously passed from the bile duct into the duodenum. During the follow-up period, over a mean of 7.1 years (range 3.7-9.3 years), no recurrence of BDSs was observed in any patient. LIMITATIONS: Small number of patients. CONCLUSIONS: Although BDSs are rare in pediatric patients, EPBD may be a safe and effective technique for the management of such stones in some children.

[One case of pancreatic mucinous carcinoma discovered due to acute pancreatitis].

The patient was a woman, aged 69, diagnosed with acute pancreatitis by a local physician; simultaneously, with US, a low-echo tumor was indicated in the pancreas' uncinate process. Diagnosis was made of acute pancreatitis resulting from a pancreatic IPMN, and the patient was referred. Ultrasound showed hypoechoic tumor images accompanied by posterior echo enhancement. With radiography-CT, from the pancreas parenchymal phase, the peripheral portion was densely stained, while internally, images showed densely stained dendriforms towards the equilibrium phase. With MRI T1-weighted images, there was appearance at low intensity, and with T2-weighted images, there was appearance at high intensity; with MRCP, there was depiction at relatively high intensity. In the final pathological diagnosis, there was prominent formation of mucinous nodules, and mucinous carcinoma including large quantity of mucous.