Randomized controlled study of gemcitabine plus S-1 combination chemotherapy versus gemcitabine for unresectable pancreatic cancer.

Purpose: The aim of this study was to evaluate efficacy and safety of gemcitabine plus S-1 (GS) combination chemotherapy in patients with unresectable pancreatic cancer.

Methods: Patients were randomly assigned to receive GS (oral S-1 60 mg/m(2) daily on days 1-15 every 3 weeks and gemcitabine 1,000 mg/m(2) on days 8 and 15) or gemcitabine (1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks). The primary endpoint was progression-free survival (PFS).

Metformin, a diabetes drug, eliminates tumor-initiating hepatocellular carcinoma cells.

Metformin has been widely used as an oral drug for diabetes mellitus for approximately 60 years. Interestingly, recent reports showed that metformin exhibited an anti-tumor action in a wide range of malignancies including hepatocellular carcinoma (HCC). In the present study, we investigated its impact on tumor-initiating HCC cells.

Hypertonic saline-epinephrine local injection therapy for post-endoscopic sphincterotomy bleeding: removal of blood clots using pure ethanol local injection.

Purpose: Bleeding following endoscopic sphincterotomy (EST) is a rare but unavoidable complication of the procedure. We routinely perform local injection of hypertonic saline-epinephrine (HSE) for the treatment of post-EST bleeding. Any blood clot is removed only by irrigation with water after local injection of pure ethanol into the blood clot to cause crusting.

Factors affecting the accuracy of endoscopic transpapillary sampling methods for bile duct cancer.

Background And Aim: Various methods for endoscopic transpapillary sampling have been developed. However, the factors affecting the accuracy of these methods for bile duct cancer are unknown. The aim of the present study was to determine the factors affecting the accuracy of endoscopic transpapillary sampling methods.

Erlotinib prolongs survival in pancreatic cancer by blocking gemcitabine-induced MAPK signals.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers worldwide. Although many regimens have been used for PDAC treatment, the combination of the EGF receptor (EGFR) inhibitor erlotinib with gemcitabine has been the only molecular-targeted drug tested so far that has been superior to gemcitabine alone. The mechanism underlying this effective combinational regimen remains unknown.

Use of F-18 fluorodeoxyglucose positron emission tomography with dual-phase imaging to identify intraductal papillary mucinous neoplasm.

Background & Aims: We investigated the usefulness of dual-phase F-18 fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) to differentiate benign from malignant intraductal papillary mucinous neoplasms (IPMNs) and to evaluate branch-duct IPMNs.

Methods: We used FDG-PET/CT to evaluate IPMNs in 48 consecutive patients who underwent surgical resection from May 2004 to March 2012. IPMNs were classified as benign (n = 16) or malignant (n = 32) on the basis of histology analysis.

Clinical usefulness of repeated pancreatic juice cytology via endoscopic naso-pancreatic drainage tube in patients with pancreatic cancer.

Background: Cytological examination of pancreatic juice obtained during endoscopic retrograde cholangiopancreatography (ERCP) is well established, but its sensitivity for pancreatic cancer has not been satisfactory. The aim of this study was to evaluate the usefulness of repeated pancreatic juice cytology (PJC) via the endoscopic naso-pancreatic drainage (ENPD) tube in patients with pancreatic cancer compared with conventional PJC.

Methods: We retrospectively investigated 139 patients with pancreatic disease.

Endoscopic sphincterotomy combined with large balloon dilation for removal of large bile duct stones.

Background/aims: Recently, there have been sporadic reports of lithotomy using endoscopic sphincterotomy combined with large balloon dilation (EPLBD) against large or multiple bile duct stones. However, there are not many reports so far concerning this procedure. Therefore, we decided to discuss the results of EPLBD against large or multiple bile duct stones.

Aldehyde dehydrogenase 1 is associated with recurrence-free survival but not stem cell-like properties in hepatocellular carcinoma.

Aim:   It has been reported that aldehyde dehydrogenase 1 A1 (ALDH1) could be not only a normal stem cell marker but also a cancer stem cell marker. ALDH1 expression could be a predictor of poor prognosis in a wide range of cancers. However, the role of ALDH1 in hepatocellular carcinoma (HCC) remains unclear.

Current situation of endoscopic treatment for common bile duct stones.

Background/aims: The progression of endoscopy and devices as well as newly developed treatment methods have enabled endoscopic lithotomy. In this study, we examined to what degree is it possible to endoscopically treat patients who are diagnosed as having common bile duct stones.

Methodology: Lithotomy was conducted using a backward side-viewing endoscope for patients without surgical history of upper gastrointestinal tract and patients with stomach reconstructed with Billroth-I method, using an ordinary endoscope for patients with stomach reconstructed with Billroth-II method (Bil-II) and using a double balloon endoscope for patients with difficulty in reaching the papilla or patients of Roux-en-Y anastomosis (R-Y).

New cannulation method for pancreatic duct cannulation-bile duct guidewire-indwelling method.

The patient was a 58-year-old male with symptomatic alcoholic chronic pancreatitis. Since a 10 mm calculus was observed in the pancreatic body and abdominal pain occurred due to congestion of pancreatic juice, endoscopic retrograde cholangiopancreatography was conducted for assessment of the pancreatic duct and treatment of pancreatic calculus. Pancreatogram was slightly and insufficiently obtained by injecting the contrast media via the common channel of the duodenal main papilla.

Different subtypes of intraductal papillary mucinous neoplasm in the pancreas have distinct pathways to pancreatic cancer progression.

Background: Intraductal papillary mucinous neoplasm (IPMN) is recognized as a precursor lesion to pancreatic cancer, a unique pathological entity. IPMN has subtypes with different clinical characteristics. However, the molecular mechanisms of cancer progression from IPMN remain largely unknown.

Transpancreatic precut papillotomy in patients with difficulty in selective biliary cannulation.

Background/aims: Transpancreatic precut papillotomy (TPPP) is considered as an effective method in patients with difficulty in selective biliary cannulation. However, the use of placing a pancreatic duct stent as a measure against post-ERCP pancreatitis has not been clarified. Here we examine the methods of implementing TPPP safely.

Inhibiting Cxcr2 disrupts tumor-stromal interactions and improves survival in a mouse model of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal neoplasms, is characterized by an expanded stroma with marked fibrosis (desmoplasia). We previously generated pancreas epithelium-specific TGF-β receptor type II (Tgfbr2) knockout mice in the context of Kras activation (mice referred to herein as Kras+Tgfbr2KO mice) and found that they developed aggressive PDAC that recapitulated the histological manifestations of the human disease. The mouse PDAC tissue showed strong expression of connective tissue growth factor (Ctgf), a profibrotic and tumor-promoting factor, especially in the tumor-stromal border area, suggesting an active tumor-stromal interaction.

Pancreatic duct guidewire-indwelling method for patients resistant to selective biliary cannulation and usefulness of pre-cut papillotomy following unsuccessful biliary cannulation with pancreatic duct guidewire-indwelling method.

Background/aims: Pancreatic duct guidewire-indwelling method (P-GW) is effective when selective biliary cannulation (SBC) has failed, but neither its true success rate nor a salvage technique have been established. In this study, we examined the usefulness of pre-cut papillotomy employing a pancreatic duct guidewire as the salvage treatment after unsuccessful SBC under P-GW.

Methodology: P-GW was conducted in 55 patients.

Utility of placement of pancreatic duct spontaneous dislodgement stent for prevention of post-ERCP pancreatitis in patients with difficulty in selective biliary cannulation.

Background/aims: To examine the utility of placement of pancreatic duct spontaneous dislodgement stents for prevention of post-ERCP pancreatitis in patients with difficulty in selective biliary cannulation.

Methodology: The incidence of pancreatitis was compared between the group with P(+) pancreatic duct spontaneous dislodgement stent placed for prevention of post-ERCP pancreatitis and the group without P(-) in patients with difficulty in selective biliary cannulation.

Results: The final success rate of selective biliary cannulation was 94.

3-Deazaneplanocin A is a promising therapeutic agent for the eradication of tumor-initiating hepatocellular carcinoma cells.

Recent advances in stem cell biology have identified tumor-initiating cells (TICs) in a variety of cancers including hepatocellular carcinoma (HCC). Polycomb group gene products such as BMI1 and EZH2 have been characterized as general self-renewal regulators in a wide range of normal stem cells and TICs. We previously reported that Ezh2 tightly regulates the self-renewal and differentiation of murine hepatic stem/progenitor cells.

Altered composition of fatty acids exacerbates hepatotumorigenesis during activation of the phosphatidylinositol 3-kinase pathway.

Background & Aims: Some clinical findings have suggested that systemic metabolic disorders accelerate in vivo tumor progression. Deregulation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is implicated in both metabolic dysfunction and carcinogenesis in humans; however, it remains unknown whether the altered metabolic status caused by abnormal activation of the pathway is linked to the protumorigenic effect.

Methods: We established hepatocyte-specific Pik3ca transgenic (Tg) mice harboring N1068fs*4 mutation.

Apoptosis signal-regulating kinase 1 and cyclin D1 compose a positive feedback loop contributing to tumor growth in gastric cancer.

Mitogen-activated protein kinase (MAPK) pathways regulate multiple cellular functions and are highly active in many types of human cancers. Apoptosis signal-regulating kinase 1 (ASK1) is an upstream MAPK involved in apoptosis, inflammation, and carcinogenesis. This study investigated the role of ASK1 in the development of gastric cancer.

Reduced expression of RAS protein activator like-1 in gastric cancer.

RAS signaling is frequently deregulated in human neoplasms. However, RAS mutations have been found in only a small proportion of human gastric cancers, implicating other mechanisms in the activation of RAS signaling in gastric tumorigenesis. We have previously reported that decreased expression of RAS protein activator like-1 (RASAL1), a member of the RAS-GTPase-activating proteins that switch off RAS activity, contributes to colon tumor progression.

Gastric cancer cell line Hs746T harbors a splice site mutation of c-Met causing juxtamembrane domain deletion.

Receptor tyrosine kinases (RTKs) are involved in oncogenesis and disease progression for many cancers. Inhibitors targeting them are vigorously developed and some of them are tested in the clinical setting. Amplifications of certain RTKs (c-Met, FGFR2 and ErbB2) have been associated with human gastric cancer progression.

Prognostic significance of genetic alterations detected by high-density single nucleotide polymorphism array in gastric cancer.

We sought to identify genomic changes that could be useful for clinical application, focusing on chromosomal instability and using a high-density single nucleotide polymorphism (SNP) array. We analyzed 34 gastric cancer cell lines for areas of DNA that exhibited copy number changes using the Affymetrix GeneChip Human Mapping 50 K Arrays. The results obtained with the cell lines were verified in 42 gastric cancer tissues using genomic PCR, quantitative real-time PCR, and loss of heterozygosity (LOH) analyses.

Macroscopic morphologic subtypes of laterally spreading colorectal tumors showing distinct molecular alterations.

Recent advances in colonoscopic techniques have resulted in more frequent detection of superficial-type colorectal tumors, that is, laterally spreading tumors (LSTs), although little is known about the characteristic clinical features and genetic alterations of LSTs. To elucidate the molecular characteristics of LSTs, genetic alterations in the KRAS, BRAF and PIK3CA genes and abnormal expression of the p53, beta-catenin and MYC proteins were analyzed using direct DNA sequencing and immunohistochemistry for 50 protruded-type tumors (Protruded), 35 granular-type LSTs (LST-G) and 19 nongranular-type LSTs (LST-NG). In addition, loss of heterozygosity (LOH) close to the adenomatous polyposis coli (APC) gene (5q21) was examined in these tumors.

Cholangiopancreatography troubleshooting: the usefulness of endoscopic retrieval of migrated biliary and pancreatic stents.

Background: Stent migration in the hepatopancreatic duct might arise as one of the rare complications associated with biliary or pancreatic stenting. Although there are some procedures to retrieve the migrated stent, including surgical, percutaneous, and endoscopic approaches, endoscopy should be attempted first because it is least invasive. This study set out to evaluate the usefulness of endoscopic retrieval of migrated biliary and pancreatic stents.