Alternative Lengthening of Telomeres in Primary Pancreatic Neuroendocrine Tumors Is Associated with Aggressive Clinical Behavior and Poor Survival.

Alternative lengthening of telomeres (ALT), a telomerase-independent telomere maintenance mechanism, is strongly associated with ATRX and DAXX alterations and occurs frequently in pancreatic neuroendocrine tumors (PanNET). In a Korean cohort of 269 surgically resected primary PanNETs and 19 sporadic microadenomas, ALT status and nuclear ATRX and DAXX protein expression were assessed and compared with clinicopathologic factors. In PanNETs, ALT or loss of ATRX/DAXX nuclear expression was observed in 20.

Generation and molecular characterization of pancreatic cancer patient-derived xenografts reveals their heterologous nature.

Pancreatic ductal adenocarcinoma (PDAC) is the most challenging type of cancer to treat, with a 5-year survival rate of <10%. Furthermore, because of the large portion of the inoperable cases, it is difficult to obtain specimens to study the biology of the tumors. Therefore, a patient-derived xenograft (PDX) model is an attractive option for preserving and expanding these tumors for translational research.

Malignant pancreatic serous cystic neoplasms: systematic review with a new case.

Background: This study analyzes the clinicopathologic and radiologic characteristics of malignant serous cystic neoplasm (SCN) of the pancreas through systematic review and an institutional case report.

Methods: A comprehensive literature search was performed in the MEDLINE database to identify studies on malignant SCNs of the pancreas that had detailed clinicopathologic and radiologic information. A computerized systematic search of our institutional database was also performed to identify cases of malignant SCN for addition to the systematic review.

A melanin-bleaching methodology for molecular and histopathological analysis of formalin-fixed paraffin-embedded tissue.

Removal of excessive melanin from heavily pigmented formalin-fixed paraffin-embedded (FFPE) melanoma tissues is essential for histomorphological and molecular diagnostic assessments. Although there have been efforts to address this issue, current methodologies remain complex and time-consuming, and are not suitable for multiple molecular applications. Herein, we have developed a robust and rapid melanin-bleaching methodology for FFPE tissue specimens.

Variability in the lymph node retrieval after resection of colon cancer: Influence of operative period and process.

The purpose of this study was to evaluate variations in the number of retrieved lymph nodes (LNs) over time and to determine the factors that influence the retrieval of <12 LNs during colon cancer resection.Patients with colon cancer who were surgically treated between 1997 and 2013 were identified from our institutional tumor registry. Patient, tumor, and pathologic variables were evaluated.

Chronic intractable diarrhea caused by gastrointestinal mastocytosis.

As mast cells have been highlighted in the pathogenesis of diarrhea-predominant irritable bowel syndrome, a new term "mastocytic enterocolitis" was suggested by Jakate and colleagues to describe an increase in mucosal mast cells in patients with chronic intractable diarrhea and favorable response to treatment with antihistamines. Although it is not an established disease entity, two cases have been reported in the English medical literature. Here, for the first time in Asia, we report another case of chronic intractable diarrhea caused by gastrointestinal mastocytosis.

Paired Primary and Metastatic Tumor Analysis of Somatic Mutations in Synchronous and Metachronous Colorectal Cancer.

Purpose: Although the mutation status of is highly concordant in primary and metastatic lesions, it has not been generalized to other major pathway genes.

Materials And Methods: In this study, 41 genes were evaluated and the mutational profiles were compared in 46 colorectal cancer patients with paired surgical specimens of primary and metastatic lesions: synchronous (n=27) and metachronous (n=19) lesions. A high-throughput mass spectrometry-based genotyping platform validated by orthogonal chemistry, OncoMap v.

Overexpression of ankyrin1 promotes pancreatic cancer cell growth.

The methylation status of a promoter influences gene expression and aberrant methylation during tumor development has important functional consequences for pancreatic and other cancers. Using methylated CpG island amplification and promoter microarrays, we identified ANK1 as hypomethylated in pancreatic cancers. Expression analysis determined ANK1 as commonly overexpressed in pancreatic cancers relative to normal pancreas.

Recent Updates on Neuroendocrine Tumors From the Gastrointestinal and Pancreatobiliary Tracts.

Context: -Gastrointestinal (GI) and pancreatobiliary tracts contain a variety of neuroendocrine cells that constitute a diffuse endocrine system. Neuroendocrine tumors (NETs) from these organs are heterogeneous tumors with diverse clinical behaviors. Recent improvements in the understanding of NETs from the GI and pancreatobiliary tracts have led to more-refined definitions of the clinicopathologic characteristics of these tumors.

Clinicopathologic and prognostic associations of KRAS and BRAF mutations in small intestinal adenocarcinoma.

Activating KRAS and/or BRAF mutations have been identified as predictors of resistance to anti-epidermal growth factor receptor (EGFR) chemotherapy in colorectal cancer. But the status of KRAS and BRAF mutations and their clinicopathologic and prognostic significance has not been extensively evaluated in small intestinal adenocarcinomas. In this work, the KRAS and BRAF genes in 190 surgically resected small intestinal adenocarcinoma cases were sequenced and their association with various clinicopathologic variables, including survival of the patients, was analyzed.

Surgical and Oncological Factors Affecting the Successful Engraftment of Patient-derived Xenografts in Pancreatic Ductal Adenocarcinoma.

Background: To effectively use pancreatic cancer patient-derived xenograft (PDX) models in translational research, successful PDX engraftment of surgical specimens in immune-deficient mice is needed.

Materials And Methods: A total of 102 patients underwent pancreatic cancer resection using various procedures. Tumor tissue from all patents was implanted subcutaneously into mice.

Intravoxel incoherent motion MRI for monitoring the therapeutic response of hepatocellular carcinoma to sorafenib treatment in mouse xenograft tumor models.

Background With the introduction of targeted therapies, there has been a growing need for non-invasive imaging methods which accurately evaluate therapeutic effects and overcome the limitations of tumor size-based therapeutic response assessments. Purpose To assess diagnostic values of intra-voxel incoherent motion (IVIM) imaging in evaluating therapeutic effects of sorafenib on hepatocellular carcinoma (HCC) using mouse xenograft model. Material and Methods Twenty-four mice bearing Huh-7 were divided into a control group and two treatment groups received sorafenib doses of 5 mg/kg (5 mg-Tx) or 30 mg/kg (30 mg-Tx).

Thread sign in biliary intraductal papillary mucinous neoplasm: a novel specific finding for MRI.

Objectives: To evaluate thread sign of biliary intraductal papillary mucinous neoplasm (B-IPMN) on magnetic resonance imaging (MRI).

Methods: Thread sign was defined as intraductal linear or curvilinear hypointense striations. Two radiologists independently evaluated the presence and location of thread sign on MR cholangiography (thin-slice, thick-slab and 3D MRC) and axial MR images (T2 TSE, T2 HASTE and DWI) in patients with B-IPMN (n = 38) and in matched control groups with benign (n = 36) or malignant (n = 35) biliary diseases.

Alpha-synuclein in gastric and colonic mucosa in Parkinson's disease: Limited role as a biomarker.

Background: Gastric and colonic alpha-synuclein immunoreactivity has been reported in patients with Parkinson's disease (PD). However, enteric alpha-synuclein also has been reported in healthy individuals.

Objectives: We aimed to investigate the utility of alpha-synuclein immunoreactivity from gastric and colonic mucosal tissues obtained by routine endoscopy to detect PD, and to correlate the pathological burden of alpha-synuclein with motor and nonmotor features of PD.

Is Pathologic Near-Total Regression an Appropriate Indicator of a Good Response to Preoperative Chemoradiotherapy Based on Oncologic Outcome of Disease?

We evaluated the oncologic outcomes of patients with rectal cancer who demonstrated pathologic near-total regression (NTR) after preoperative chemoradiotherapy (PCRT) and compared with total regression (TR). Pathologic NTR in rectal cancer by tumor regression grade (TRG) is usually considered to indicate a good response, when evaluating tumor response to PCRT. We retrospectively analyzed the outcomes in 263 patients who received PCRT for advanced T3/4 or N+ rectal cancer followed by radical resection.

Postresection Outcomes of Combined Hepatocellular Carcinoma-Cholangiocarcinoma, Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

Introduction: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is rare. This study investigated the clinicopathological features of cHCC-CC and compared the postresection survival outcomes of cHCC-CC, hepatocellular carcinoma (HCC), and intrahepatic cholangiocarcinoma (IHC).

Methods: Between January 2000 and September 2012, 53 patients with cHCC-CC underwent tumor resection, accounting for 1.

A Revised Classification System and Recommendations From the Baltimore Consensus Meeting for Neoplastic Precursor Lesions in the Pancreas.

International experts met to discuss recent advances and to revise the 2004 recommendations for assessing and reporting precursor lesions to invasive carcinomas of the pancreas, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, and other lesions. Consensus recommendations include the following: (1) To improve concordance and to align with practical consequences, a 2-tiered system (low vs. high grade) is proposed for all precursor lesions, with the provision that the current PanIN-2 and neoplasms with intermediate-grade dysplasia now be categorized as low grade.

Prognostic Value of Somatostatin Receptor Subtypes in Pancreatic Neuroendocrine Tumors.

Objectives: Studies on the expression of somatostatin receptor (SSTR) subtypes in pancreatic neuroendocrine tumors (PNETs) are rare. The aim of this study was to determine the expression of the SSTR subtypes via immunohistochemistry analyses and assess the correlation between SSTR subtype expression and prognosis.

Methods: We examined 199 patients with PNET who underwent surgical resection between January 1995 and December 2010 at the Asan Medical Center.

Shear Wave Elastography for Assessment of Steatohepatitis and Hepatic Fibrosis in Rat Models of Non-Alcoholic Fatty Liver Disease.

The purpose of this study was to evaluate shear wave elastography (SWE) as a method for determining the severity of non-alcoholic fatty liver disease (NAFLD) and the stage of hepatic fibrosis, as well as the major determinants of liver elasticity among the various histologic and biomolecular changes associated with NAFLD. Rat NAFLD models with various degrees of NAFLD severity were created and imaged using SWE. The explanted livers were subjected to histopathologic evaluation and RNA expression analysis.

Hypervascular solid-appearing serous cystic neoplasms of the pancreas: Differential diagnosis with neuroendocrine tumours.

Purpose: To describe imaging findings of arterial hypervascular solid-appearing serous cystic neoplasms (SCNs) of the pancreas on CT and MR and determine imaging features differentiating them from neuroendocrine tumours (NETs).

Materials And Methods: We retrospectively identified 15 arterial hypervascular solid-appearing SCNs and randomly chose 30 size-matched pancreatic NETs. On CT, two radiologists in consensus assessed the size, morphology, and CT attenuation.

A combination of molecular markers and clinical features improve the classification of pancreatic cysts.

Background & Aims: The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients.

Methods: We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms).

Prognostic value of CT findings to predict survival outcomes in patients with pancreatic neuroendocrine neoplasms: a single institutional study of 161 patients.

Objectives: To evaluate the prognostic value of CT to predict recurrence-free and overall survival in patients with pancreatic neuroendocrine neoplasms (PanNENs).

Methods: Between January 2004 and December 2012, 161 consecutive patients who underwent preoperative triphasic CT and surgical resection with curative intent for PanNENs were identified. The tumour consistency, margin, presence of calcification, pancreatic duct dilatation, bile duct dilatation, vascular invasion, and hepatic metastases were evaluated.

Pyruvate kinase isoenzyme M2 is a therapeutic target of gemcitabine-resistant pancreatic cancer cells.

Despite its wide use as a first-line therapeutic agent, gemcitabine has shown limited efficacy in advanced pancreatic cancer due to chemoresistance by as yet unidentified mechanisms. Our goal here was to identify molecular features involved in gemcitabine chemoresistance. Pyruvate kinase M2 (PKM2), a key enzyme of aerobic glycolysis, has recently emerged as an important therapeutic target for cancer treatment.

Intraductal tubulopapillary neoplasms of the bile ducts: clinicopathologic, immunohistochemical, and molecular analysis of 20 cases.

Intraductal tubulopapillary neoplasm is a well-established entity in the pancreas. A similar, if not identical, tumor occurs also in the biliary tract. We conducted a multicenter study of 20 such lesions, focusing on their clinicopathologic characteristics and molecular profile.