An 82-year-old woman presented to our hospital with chief complaints of lower abdominal pain and nausea. Contrast- enhanced CT showed ileus of sigmoid colon cancer and a solitary splenic tumor. A metallic stent was placed for the primary lesion.
View Article and Find Full Text PDFBackground: In distal pancreatectomy (DP), the position of the pancreas division line (PDL) changes depending on the location or nature of the tumor. Here, we investigated the relationship between PDL and postoperative complications after DP.
Methods: We retrospectively analyzed data of 140 patients who underwent DP at Tokyo Medical and Dental University Hospital between January 2011 and September 2018.
Background: Some patients with pancreatic ductal adenocarcinoma (PDAC) demonstrate a reticular pattern around the superior mesenteric artery (SMA) in computed tomography scans. This study aimed to clarify the clinical significance of the reticular pattern in pancreatic head cancer.
Methods: A total of 91 patients with pancreatic head cancer, who underwent upfront pancreaticoduodenectomy between 2004 and 2017, were included.
Genomic analyses have recently discovered the malignant subtype of human intrahepatic cholangiocarcinoma (ICC) characterized by frequent mutations of chromatin remodeling gene ARID1A; however, the biological and molecular functions still remain obscure. We here examined the clinical and biological significances of ARID1A deficiency in human ICC. Immunohistochemical analysis demonstrated that the loss of ARID1A was an independent prognostic factor for overall survival of ICC patients (P = 0.
View Article and Find Full Text PDFPurpose: Because it is unknown whether adjusting the dose of sunitinib can benefit patients with pancreatic neuroendocrine neoplasms (Pan-NENs), this retrospective study examined maximum tumor shrinkage rates and prognoses in patients with and without low doses of sunitinib administration.
Methods: Eighty-seven patients with metastatic and unresectable neoplasms, treated with sunitinib for > 1 month, were divided into a low-dose (LD) or high-dose (HD) group. The tumor response rates were investigated over time using computed tomography according to the response evaluation criteria in solid tumors criteria.
Objectives: Pancreatic fistula after distal pancreatectomy (DP) remains an unsolved problem, and postoperative CT imaging often demonstrates fluid collection (FC) around the pancreatic remnant. This study sought to clarify the clinical implications of FC.
Methods: This study enrolled 146 patients who underwent DP.
Background: The prognostic importance of the neuroendocrine (NE) markers involving neural cell adhesion molecule (NCAM) has been unclear enough to be adopted for WHO classification in patients with pancreatic neuroendocrine neoplasms (Pan-NENs). This study aimed to elucidate whether the three NE markers such as chromogranin A, synaptophysin, and NCAM decide prognoses for patients with well-differentiated tumors.
Methods: Between April 2002 and October 2018, 217 patients were included in this study.
Background: Hepatocellular carcinoma (HCC) is a heterogeneous disease with various etiological factors, and ranks as the second leading cause of cancer-related mortality worldwide due to multi-focal recurrence. We herein identified three major subtypes of HCC by performing integrative analysis of two omics data sets, and clarified that this classification was closely correlated with clinicopathological factors, immune profiles and recurrence patterns.
Methods: In the test study, 183 tumor specimens surgically resected from HCC patients were collected for unsupervised clustering analysis of gene expression signatures and comparative analysis of gene mutations.
Although genomic analysis have recently discovered the malignant subtype of human pancreatic ductal adenocarcinoma (PDAC) characterized by frequent mutations of histone demethylase KDM6A, the biological and molecular roles still remain obscure. We herein elucidated the clinical and biological impacts of KDM6A deficiency on human PDAC and identified the therapeutic potential by pathological and molecular evaluation. Immunohistochemical analysis suggested that loss of KDM6A in cancerous tissues was an independent prognostic factor for both recurrence-free and overall survival in the 103 tumor specimens surgically resected from patients with PDAC.
View Article and Find Full Text PDFBackground And Aim: To improve the prognosis of cholangiocarcinoma, we investigated potential biomarkers that may enable the selection of patients for whom postoperative adjuvant chemotherapy is likely effective.
Methods: The cohort of this retrospective study included 170 surgically resected cholangiocarcinoma patients, 26 with gemcitabine adjuvant chemotherapy (GEM group), 36 with S-1 adjuvant chemotherapy (S-1 group), and 103 receiving no adjuvant chemotherapy (NC group). Propensity score matching was performed to adjust patient backgrounds; 36 patients from the NC group then were selected.
Objective: To predict metachronous liver metastasis after pancreatectomy for pancreatic neuroendocrine neoplasms (Pan-NENs).
Summary Of Background Data: Liver metastasis determines the prognosis of patients with Pan-NENs, but no index exists in the WHO 2017 classification for this prediction.
Methods: Between April 2014 and March 2018, resected primary tumors from 20 patients with or without simultaneous liver metastasis were examined using genome-wide gene expression analysis.
Introduction: The use of laparoscopic distal pancreatectomy (LDP) is increasing worldwide. It is important for surgeons to predict preoperatively the difficulty and risks of a surgery. However, very few reports have evaluated the impact of patient or tumor factors on the difficulty of LDP.
View Article and Find Full Text PDFPurpose: The 2017 revised World Health Organization classification of pancreatic neuroendocrine neoplasms classified conventional G3 tumors into well-differentiated (NET-G3) and poorly differentiated (NEC-G3) tumors. However, guidelines for selection of drug therapy were not established in the 2017 revision. This study aimed to elucidate the rates of maximum tumor reduction of sunitinib, progression-free survival, and overall survival in the new classification.
View Article and Find Full Text PDFPancreatic neuroendocrine tumors (PanNETs) have considerable malignant potential. Frequent somatic mutations and loss of DAXX protein expression have been found in PanNETs. DAXX is known as a transcriptional repressor; however, molecular functions underlying DAXX loss remain unclear in PanNETs.
View Article and Find Full Text PDFMetabolic syndrome is a newly identified risk factor for hepatocellular carcinoma (HCC); however, tumor-specific biomarkers still remain unclear. We performed cross-species analysis to compare gene signatures of HCC from human patients and melanocortin 4 receptor-knockout mice, which develop HCC with obesity, insulin resistance, and dyslipidemia. Unsupervised hierarchical clustering and principle component analysis of 746 differentially expressed orthologous genes classified HCC of 152 human patients and melanocortin 4 receptor-knockout mice into two distinct subgroups, one of which included mouse HCC and was causatively associated with metabolic risk factors.
View Article and Find Full Text PDFDecrease in blood concentration of branched-chain amino acids, especially leucine, is known to promote liver carcinogenesis in patients with chronic liver disease, but the mechanism is unclear. We herein established hepatocellular carcinoma (HCC) cells knocked out for DEPDC5 by using the CRISPR/Cas9 system, and elucidated that cell viability of the DEPDC5 knockout (DEPDC5-KO) cells was higher than that of the DEPDC5 wild-type (DEPDC5-WT) under leucine starvation. Considering that autophagy deficiency might be involved in acquired resistance to leucine deprivation, we observed reduction of LC3-II followed by accumulation of p62 in the DEPDC5-KO, which induced reactive oxygen species (ROS) tolerance.
View Article and Find Full Text PDFBackground: A novel morphological classification using resected specimens predicted malignant potential and prognosis in patients with pancreatic neuroendocrine tumors (P-NETs). The aim of this study was to examine the predictive ability of morphological diagnoses made using non-invasive multi-detector computed tomography (MDCT) in P-NETs.
Methods: Between 2002 and 2015, 154 patients were diagnosed with P-NETs at the Tokyo Medical and Dental University, and 82 patients who underwent surgical treatment were enrolled.
J Hepatobiliary Pancreat Sci
July 2017
Background: Pancreaticoduodenectomy (PD) is the standard surgical procedure for treating pancreatic head cancers. Considerable knowledge of proximal jejunal and pancreatic vein anatomy is a prerequisite for performing PD surgery safely, yet there appear to be no detailed descriptions of first and second jejunal vein (J1V, J2V) anatomy available in the literature.
Study Design: Adults with hepatobiliary-pancreatic disease underwent multidetector-row computed tomography with intravenous contrast (n = 155), and SYNAPSE 3D (Fujifilm Medical, Tokyo, Japan) was used to generate 3D-CT images.
Antiangiogenic therapy is initially effective for several solid tumors including hepatocellular carcinoma; however, they finally relapse and progress, resulting in poor prognosis. We here established drug-tolerant subclones of human hepatocellular carcinoma cells by long-term treatment with VEGF receptor (VEGFR) inhibitor and serial transplantation in immunocompromised mice (total 12 months), and then compared them with the parental cells in molecular and biological features. Gene expression profiles elucidated a G-actin monomer binding protein thymosin β 4 (Tβ4) as one of the genes enriched in the resistant cancer cells relative to the initially sensitive ones.
View Article and Find Full Text PDFBackground & Aims: Recent genomic studies have identified frequent mutations of AT-rich interactive domain 2 (ARID2) in hepatocellular carcinoma (HCC), but it is not still understood how ARID2 exhibits tumor suppressor activities.
Methods: We established the ARID2 knockout human HCC cell lines by using CRISPR/Cas9 system, and investigated the gene expression profiles and biological functions.
Results: Bioinformatic analysis indicated that UV-response genes were negatively regulated in the ARID2 knockout cells, and they were sensitized to UV irradiation.
J Hepatobiliary Pancreat Sci
December 2016
Background: The most reliable index to predict the safety of hepatectomy for patients with poor liver function remains unknown. We aimed to construct a novel preoperative index to predict early liver failure (ELF) and mortality due to recurrence-free liver failure (MLF) after hepatectomy.
Methods: Between 2000 and 2012, 385 consecutive patients with hepatocellular carcinoma undergoing curative minor hepatectomy were divided into two sequential cohorts: training set (n = 143) and validation set (n = 242), and observed until 2015.
Background: For the establishment of personalized therapy, we investigated biomarkers that can contribute to the selection of adjuvant therapy for pancreatic ductal adenocarcinoma (PDAC).
Methods: Between 2005 and 2014, of 141 consecutive patients with PDAC who underwent R0 or R1 resection, 61 patients given gemcitabine and 31 patients given S-1 as adjuvant therapy were enrolled. We evaluated the correlation between treatment outcomes and the expressions of intratumoral human antigen R (HuR), human equilibrative nucleoside transporter 1 (hENT1), thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD).
Proteasome activity is significantly increased in advanced cancers, but its role in cancer initiation is not clear, due to difficulties in monitoring this process in vivo. We established a line of transgenic mice that carried the ZsGreen-degron(ODC) (Gdeg) proteasome reporter to monitor the proteasome activity. In combination with Pdx-1-Cre;LSL-Kras(G12D) model, proteasome activity was investigated in the initiation of precancerous pancreatic lesions (PanINs).
View Article and Find Full Text PDFPurpose: Pancreatic neuroendocrine neoplasm (Pan-NEN) representing approximately 1.3 % of pancreatic malignancy cases in incidence has been a so rare disease that it remains major problem to analyze the malignant potential. The aim of this study was to verify whether the macroscopic morphology of Pan-NEN, a novel pathological classification, contributes to malignant potential.
View Article and Find Full Text PDFPatients with pancreatic cancer typically develop tumor invasion and metastasis in the early stage. These malignant behaviors might be originated from cancer stem cells (CSCs), but the responsible target is less known about invisible CSCs especially for invasion and metastasis. We previously examined the proteasome activity of CSCs and constructed a real-time visualization system for human pancreatic CSCs.
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