Real-World Analysis of the Correlation between Overall Survival and Progression-Free Survival in Advanced Pancreatic Cancer: Results of NAPOLEON-1 and 2 Studies.

Introduction: Fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) improve overall survival (OS) and progression-free survival (PFS) in patients with pancreatic cancer, compared with gemcitabine (GEM). However, whether PFS is a surrogate marker of OS in pancreatic cancer chemotherapy focusing on FOLFIRINOX or GEM plus nab-paclitaxel remains unknown. We aimed to verify whether PFS can be a surrogate marker of OS in prognosis prediction.

A multicenter retrospective observational NAPOLEON2 study of nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable pancreatic cancer.

Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer. However, there are limited clinical data on its efficacy and safety in the real-world. We therefore initiated a retrospective and prospective observational study (NAPOLEON-2).

Rectal Paraganglioma.

A 57-year-old woman was admitted with lower abdominal pain and bloody bowel discharge. She was diagnosed with rectal tumor by colonoscopy, and a biopsy was performed. Surgery was performed, resulting in a diagnosis of rectal paraganglioma.

A Prospective, Multicenter Phase II Study of the Efficacy and Feasibility of 15-minute Panitumumab Infusion Plus Irinotecan for Oxaliplatin- and Irinotecan-refractory, KRAS Wild-type Metastatic Colorectal Cancer (Short Infusion of Panitumumab Trial).

Background: In some recently updated clinical guidelines, the fully humanized monoclonal antibody panitumumab, combined with irinotecan, has been recommended as an optional third-line chemotherapy for KRAS wild-type metastatic colorectal cancer (mCRC). The present prospective, multicenter phase II study evaluated the effectiveness and safety of short 15-minute panitumumab infusions.

Patients And Methods: From January 2011 to December 2011, patients with KRAS wild-type mCRC were enrolled at 8 centers.

[A case of a patient with splenic arteriovenous fistula associated with portal hypertension who developed refractory ascites and diarrhea as initial symptom].

A 55-year-old woman was admitted to our hospital because of diverse symptoms of portal hypertension, such as refractory ascites, diarrhea, and general malaise. Blood test revealed liver and renal dysfunction and glucose tolerance. Contrast enhancement computed tomography revealed splenic arteriovenous fistula with dilated splenic artery and vein, causing portal hypertension.

Branched-chain amino acid deficiency stabilizes insulin-induced vascular endothelial growth factor mRNA in hepatocellular carcinoma cells.

Abnormal sugar metabolism is closely related to chronic liver diseases, including hepatocellular carcinoma (HCC). We previously reported that fasting hyperinsulinemia is a poor prognostic factor for HCC patients. A recent large-scale study has shown that long-term administration of branched chain amino acids (BCAA) reduces the risk of HCC development in obese cirrhotic patients who have been diagnosed with diabetes mellitus, although the mechanism by which it does so is unclear.

Insulin-induced mTOR activity exhibits anti-hepatitis C virus activity.

The mammalian target of rapamycin (mTOR) is one of the influential molecules for the anti-hepatitis C virus (HCV) action of interferon (IFN). IFN-induced mTOR activity, independent of phosphatidylinositol-3-kinase (PI3K) and Akt, is a critical factor for anti-HCV activity. mTOR activity is involved in signal transducers and activators of transcription (STAT)-1 phosphorylation and nuclear localization, and then double-stranded RNA-dependent protein kinase (PKR) is expressed in hepatocytes.

Geranylgeranylacetone has anti-hepatitis C virus activity via activation of mTOR in human hepatoma cells.

Background: Geranylgeranylacetone (GGA), an isoprenoid compound which includes retinoids, has been used orally as an anti-ulcer drug in Japan. GGA acts as a potent inducer of anti-viral gene expression by stimulating ISGF3 formation in human hepatoma cells. This drug has few side effects and reinforces the effect of IFN when administered in combination with peg-IFN and ribavirin.

Second-line chemotherapy with irinotecan plus cisplatin after the failure of S-1 monotherapy for advanced gastric cancer.

Background: For advanced gastric cancer (AGC), second-line chemotherapy after the failure of S-1 has not yet been established. The present study aimed to retrospectively evaluate the efficacy and safety of irinotecan plus cisplatin (IP) therapy after the failure of S-1 in patients with AGC.

Methods: The subjects included 87 patients with AGC who received IP therapy as second-line chemotherapy.

Differences in prognostic factors according to viral status in patients with hepatocellular carcinoma.

The number and ratio of both HBsAg- and HCV Ab-negative hepatocellular carcinoma (HCC-nonBC) cases have been steadily increasing in Japan. The aim of this study was to examine the frequency of detection of HCC-nonBC by screening methods and to elucidate the clinical characteristics of HCC-nonBC compared with those of hepatitis C and/or B virus-associated HCC (HCC-virus). We recruited 624 patients with HCC who were diagnosed between 1982 and 2007 at the Department of Gastroenterology and Hepatology, Nagasaki University Hospital.

Relationship between regulatory T cells and the combination of pegylated interferon and ribavirin for the treatment of chronic hepatitis type C.

Background/aim: The frequency of regulatory T cells (Tregs) may be related to persistent hepatitis C virus (HCV) infection. We studied the alteration of the Treg ratio in peripheral blood mononuclear cells (PBMCs) from chronic hepatitis C patients during combination therapy compared with the Treg ratio in liver-infiltrating lymphocytes (LILs) before therapy.

Method: The study group consisted of 20 patients who were treatment-naive and had high virus titers of HCV genotype 1.

The level of fasting serum insulin, but not adiponectin, is associated with the prognosis of early stage hepatocellular carcinoma.

Impaired glucose tolerance influences the prognosis of hepatocellular carcinoma (HCC), but this mechanism is still not fully understood. We investigated the impact of the fasting serum levels of insulin and adiponectin on the prognosis of HCC and its recurrence. One hundred and forty patients with newly diagnosed HCC were enrolled in the prognosis study.

Hepatitis C virus kinetics during the first phase of pegylated interferon-alpha-2b with ribavirin therapy in patients with living donor liver transplantation.

Aim: To identify the problems of pegylated interferon (PEG IFN) with ribavirin therapy against hepatitis C virus (HCV) reinfection in living donor liver transplantation (LDLT) patients. HCV kinetics during the PEG IFN with ribavirin therapy were analyzed in LDLT patients, as well as in chronic hepatitis C (CHC) patients.

Methods: The study included 80 consecutive HCV infected patients undergoing PEG IFN with ribavirin therapy (64 CHC and 16 LDLT patients) who attended the Nagasaki University Hospital for an initial visit between January 2005 and December 2007.

Predictive value of suppressor of cytokine signal 3 (SOCS3) in the outcome of interferon therapy in chronic hepatitis C.

Aims: Suppressor of cytokine signaling 3 (SOCS3) can suppress Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling by blocking an IFN-induced protein. In this study, the relationship between SOCS3 and phosphorylation of STAT1 in the liver and outcome of interferon therapy were examined.

Methods: Prior to interferon treatment, we immunostained for SOCS3 and phosphorylated-STAT1 (P-STAT1) in 59 liver specimens from chronic hepatitis C virus (CHC) patients and compared the expression of SOCS3 and clinicopathological factors.

Portal hypertensive gastropathy with portal thrombosis successfully treated with partial splenic embolization.

A 60-year-old man with alcoholic liver cirrhosis was admitted to our hospital with severe anemia and tarry stool. Upper gastrointestinal endoscopy revealed grade 4 esophageal varices without bleeding and severe portal hypertensive gastropathy (PHG) of the fornix of the stomach with oozing. These findings suggested that PHG was the cause of progression of anemia.

Interferon-alpha-induced mTOR activation is an anti-hepatitis C virus signal via the phosphatidylinositol 3-kinase-Akt-independent pathway.

Object: The interferon-induced Jak-STAT signal alone is not sufficient to explain all the biological effects of IFN. The PI3-K pathways have emerged as a critical additional component of IFN-induced signaling. This study attempted to clarify that relationship between IFN-induced PI3-K-Akt-mTOR activity and anti-viral action.

A snack enriched with oral branched-chain amino acids prevents a fall in albumin in patients with liver cirrhosis undergoing chemoembolization for hepatocellular carcinoma.

Nutritional support may play an important role in management of liver cirrhosis (LC) associated with unresectable hepatocellular carcinoma (HCC). Total protein and albumin deteriorate in patients with LC undergoing trans-arterial chemoembolization (TACE). Therefore, in this study, we examined the hypothesis that short-term administration of branched-chain amino acids (BCAA) will prevent a fall in total protein and albumin in the perioperative period.

Predictive value of the phosphorylation of signal transducers and activators of transcription in the outcome of interferon therapy for chronic hepatitis C.

Objective: Signal transducers and activators of transcription (STATs) play a critical role in antiviral defense. To better understand pegylated interferon (IFN)-alpha and ribavirin combination therapy resistance, we examined the STAT expression in the liver.

Methods: We immunostained Phospho-STAT1 (P-STAT1) and Phospho-STAT3 (P-STAT3) in 59 hepatitis C virus (HCV)-infected liver tissues and compared the expression of these STATs proteins and the clinicopathological factors.

Study of liver-targeted regulatory T cells in hepatitis B and C virus in chronically infected patients.

Introduction: Regulatory T cells (Tregs) play a critical role in chronic viral infections. The role of Tregs in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) is unknown. This study examined the distribution and frequency of forkhead box p3(+) (Foxp3(+)) Tregs in the liver tissue and compared the clinicopathological characteristics of CHB and CHC patients.

Significance of trans-hepatic arterial chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombus.

Portal vein tumor thrombus (PVTT) is observed in a considerable number of hepatocellular carcinoma (HCC) cases. It is an exacerbating factor for patients afflicted with HCC. The sequelae of PVTT are considered to be a contraindication for the treatment of HCC in such patients.

A high glucose condition sensitizes human hepatocytes to hydrogen peroxide-induced cell death.

Oxidative stress is known to play a key role in the progression of liver disease, including non-alcoholic steatohepatitis (NASH), which is often accompanied by hyperglycemia. This study examined the influence of high glucose on oxidative stress-induced hepatic cell death. Hc cells, a normal human hepatocyte-derived cell line, were cultured in normal-to-high glucose (5.

Hepatitis B-related polyarteritis nodosa presenting necrotizing vasculitis in the hepatobiliary system successfully treated with lamivudine, plasmapheresis and glucocorticoid.

A 64-year-old man was admitted for alithiasic cholecystitis. Necrotizing vasculitis was detected in a gallbladder obtained at the cholecystectomy. Slight elevation of transaminases, HBe antigens and hepatitis B-DNA (HBV-DNA) were detected in the patient.