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Supplemental Digital Content is available in the text, Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become one of the most useful diagnostic modalities for the diagnosis of pancreatic mass. The aim of this study was to investigate the role of analyzing the minimal specimens obtained by EUS-FNA for the diagnosis of solid masses of pancreas. This study consisted of retrospective and prospective analyses. The retrospective study was performed on 116 patients who underwent EUS-FNA of solid masses for cytological smear, histological analysis, and combined analysis including immunohistochemical (IHC) staining. In the prospective study, 79 patients were enrolled to evaluate the quality and accuracy of EUS-FNA histological analysis and feasibility of IHC staining. The final diagnoses of all patients included pancreatic cancer (n = 126), nonpancreatic cancer (n = 21), other neoplasm (n = 27), and benign lesions (n = 21). In our retrospective study, the combined analysis was more sensitive than cytological analysis alone (P

Neuroblastoma (NB) is one of the most common malignant pediatric tumors that show aggressive behavior. Most advanced-stage NBs have proven refractory to many treatment modalities, and a fundamental alternative therapy, such as inhibition of biological pathways, is now being explored. Anaplastic lymphoma kinase (ALK) has recently been identified as an activation mutation in familial or high-risk sporadic NBs. We examined the prevalence of the ALK mutation in 54 NB cases (23 pre-treatment cases and 31 cases for which specimens were available before and after treatment) and the presence of the ALK mutation in various pediatric tumors. We detected the ALK mutation (F1174C and R1275Q) in 2 (3.7%) of the 54 NB specimens. Both cases showed poorly differentiated and advanced-stage NBs. No ALK mutations were detected in other pediatric tumors. The frequency of the ALK mutation was somewhat lower than that expected in Korean patients with NBs. The mutation detected in the present study was one of the hotspot mutations, including positions of F1174 and R1275 reported previously. The results of the present study suggest the possibility of potential roles of ALK inhibitors in the therapeutics of a small population of neuroblastoma carrying mutated ALK kinases.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are classified into the following four histopathologic subtypes: gastric, intestinal, pancreatobiliary, and oncocytic. However, the clinicopatholgic characteristics of IPMN subtypes have not been fully clarified. Recently, a subgroup classification of minimally invasive intraductal papillary mucinous carcinomas (MI-IPMCs) was suggested in contrast to overt invasive carcinoma from IPMCs (IC-IPMCs). The purpose of this study was to determine whether or not the pathologic subtype classification can predict prognosis and to validate the usefulness of the newly proposed diagnostic criteria of MI-IPMCs. We reviewed the clinicopathologic characteristics of 142 surgically resected cases of IPMNs. There were 54, 56, 30, and two cases of the gastric, intestinal, pancreatobiliary, and oncocytic types of IPMNs, respectively. The intestinal and pancreatobiliary types were more likely to have a main duct type. All gastric type tumors were adenomas or moderate dysplasia, whereas greater than one half of the intestinal and pancreatobiliary types were carcinomas in situ or invasive carcinomas. A significant difference in recurrence and death rate was noted for invasive carcinoma between the intestinal and pancreatobiliary types. The majority of MI-IPMCs were the intestinal type, whereas the majority of IC-IPMCs were the pancreatobiliary type. The IC-IPMC group showed a decreased recurrence-free and overall survival with statistically significance (p < 0.001 and p = 0.001, respectively). Our results suggest that the pathologic subtype classification and the newly proposed diagnostic criteria for minimal invasion may also be useful to predict prognosis of IPMNs of the pancreas.

Ataxia telangiectasia mutated kinase (ATM) and cyclin B1 are involved in cell cycle control. The prognostic significance of both molecules has not yet been investigated in pancreatic neuroendocrine tumors. The aim of this study was to evaluate the clinical and prognostic significance of ATM and cyclin B1 in patients with pancreatic neuroendocrine tumors. A total of 107 pancreatic neuroendocrine tumor specimens that were surgically resected were immunohistochemically investigated using the tissue microarray technique. Clinicopathologic results and survival were evaluated retrospectively. High expression of ATM and cyclin B1 was related to well-differentiated endocrine tumors of the World Health Organization (WHO) classification, but not related to TNM stages. The high ATM expression group (ATM ≥ 4) had a significantly smaller tumor size, lower recurrence rate, more number of functioning tumor, and well differentiation of WHO classification. The high cyclin B1 expression group (cyclin B1 ≥ 5) was related to smaller tumor size, less vascular invasion, less recurrence rate, and less death rate. However, cyclin B1 was the only significant factor for survival following multivariate analysis (p = 0.008; OR, 0.54; 95 % CI, 0.35-0.85). The current results suggested that expression of ATM and cyclin B1 may be useful markers to identify patients with poor prognosis who may benefit from close follow-up and aggressive therapy in pancreatic neuroendocrine tumors.

Objective: To compare results of liquid-based cytology (LBC) and the conventional smear method (SMEAR) when performing endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for lesions of suspected pancreatic malignancy without an on-site cytopathologist. Study Design: Fifty-eight patients were prospectively enrolled between July and December 2009. Aspirates obtained from the first needle pass were randomized either to SMEAR or LBC. Another sample from the second needle pass was allocated to the other method. The rest of the aspirates from the third or later needle passes were used for SMEAR. Diagnostic accuracy was compared and related factors were pursued. Results: Although both methods were 100% specific, LBC was inferior to SMEAR in terms of sensitivity, negative predictive value, and accuracy. However, LBC provided correct diagnoses in 2 out of 3 cases of false negatives for malignancy by SMEAR in which blood was highly contaminated. Although no factor was identified for LBC, low blood contamination and more than 3 needle passes were related with accurate diagnosis in SMEAR. Conclusion: LBC was less accurate than SMEAR when performing pancreatic EUS-FNA without an on-site cytopathologist. However, LBC might serve as a good complement to SMEAR if blood contamination is profound.

In patients with hilar cholangiocarcinoma (HC), longitudinal tumor extent is important for curative resection. The purpose of this study was to evaluate the longitudinal extents of HC using transpapillary intraductal ultrasonography (IDUS) for optimal surgical planning.From July 2006 to April 2010, a total of 42 patients with borderline resectable HC were enrolled at Samsung Medical Center, a tertiary referral hospital in Seoul, Korea. All patients were evaluated using multi-detector computed tomography (MDCT), endoscopic retrograde cholangiopancreatography (ERCP) and IDUS. The new modified Bismuth Type (MBT) classification, in which the traditional Bismuth type IV stage is divided into stages IVa and IVb, was used to determine whether the tumor invaded the left lateral section. Among the subtypes of HC, the periductal infiltrative type (PDI) and intraductal papillary neoplasm of the bile duct (IPN-B) were compared. The accuracies of CT, ERCP, and IDUS were assessed through comparison with the postoperative histology findings.A total of 42 patients were prospectively enrolled, and the tumor extent could be assessed histologically in 30 patients. The accuracies of CT, ERCP, and IDUS were 66.6%, 60%, and 90%, respectively. The accuracy of IDUS was 85.7% in 21 patients with PDI and 100% in nine patients with IPN-B.Hilar cholangiocarcinoma staging based on IDUS findings was highly accurate. We therefore highly recommend using IDUS for optimal surgical planning in patients with borderline resectable HC.