Helicobacter pylori-negative Gastric Adenocarcinoma Mimicking Verrucous Gastritis in the Antrum: A Case Report and Literature Review.

A 46-year-old man was referred to our hospital for the examination of a flat elevated lesion with an erosion-like depression, located on the greater curvature of the antrum. Endoscopic submucosal dissection was performed. Histological findings of the resected specimen demonstrated a well-differentiated tubular adenocarcinoma with a diameter of 12 mm. No atrophy was observed in the tumor-adjacent mucosa. Serum Helicobacter pylori antibody estimation and 13C-urea breath tests yielded negative results. Immunohistochemical staining was positive for both gastric mucin and intestinal mucin. The final diagnosis was well-differentiated tubular adenocarcinoma with a gastrointestinal phenotype that originated in mucosa uninfected by H. pylori.

Gallbladder Cancer with Biliary Intraepithelial Neoplasia Complicated by Pancreaticobiliary Maljunction: A Case Report.

We report herein a case of gallbladder cancer with biliary intraepithelial neoplasia (BilIN) complicated by pancreaticobiliary maljunction (PBM). A 60-year-old woman was referred to our hospital for thickening of the gallbladder wall diagnosed via ultrasonography at the referring clinic. The Radiographic images showed thickening of the gallbladder wall and a high confluence of pancreaticobiliary ducts outside the duodenal wall without dilatation of the bile duct. The amylase level in the bile duct was highly elevated. The patient was initially diagnosed with PBM without biliary dilatation, and laparoscopic cholecystectomy was performed. Histopathology of the resected specimen revealed gallbladder cancer localized in the mucosa propria with widespread BilIN. Immunohistochemical analyses showed positive results for S100P,IMP3 and p16ink4a in tumor cells, but a positive result for only IMP3 in adenocarcinoma. Expression of p53 was negative. Oncogenic KRAS mutations were not detected in tumor cells. The patient was diagnosed with gallbladder cancer with BilIN complicated by PBM. This case report may be useful in clarifying the carcinogenic process and genetic mutations for gallbladder cancer associated with PBM.

[A case of hepatic angiosarcoma detected as a small lesion].

A 72-year-old man visited for imaging examination of alcoholic cirrhosis in April 2007. Enhanced CT images were revealed a 7 mm early enhanced lesion in segment 6 of the liver. The lesion was increased gradually to 40 mm on MRI images 21 months later. We performed ultrasound liver biopsy 3 times. Histology showed angiosarcoma with high-grade atypia and it was positive for CD31, CD34 and factor VIII-related antigen. The doubling time of this tumor was 42-108 days. Although we performed transarterial chemoembolization and interleukin-2 therapy, the patient died 34 months after the initial detection of tumor. We observed the clinical course with periodic imaging examination from the early stage of hepatic angiosarcoma and obtained a pathologic diagnosis by liver biopsy.

[A case of AFP-producing gastric cancer responding to the combination of systemic chemotherapy, transcatheter arterial embolization and hepatic infusion chemotherapy].

We report a case of a 64-year-old male with a-fetoprotein(AFP)-producing gastric cancer accompanied by large liver metastases and multiple lymph node metastases. The patient's serum AFP level was 42,307 ng/mL and a biopsy specimen showed AFP-positive tumor cells immunohistochemically. Systemic chemotherapy by tegafur gimeracil oteracil potassium(S-1)and local therapy for the hepatic metastases consisting of transcatheter arterial embolization (TAE)and infusion of epirubicin(EPI)to the hepatic arteries decreased the serum AFP level and reduced the gastric cancer and metastases. Due to the increase of AFP and lymph node metastases, we had to successively change the regimen to paclitaxel(PTX), a combination of cisplatin(CDDP)/irinotecan(CPT-11)and S-1. Continuous systemic chemotherapy in combination with various drugs for gastric cancer treatment followed by TAE and hepatic infusion chemotherapy for hepatic metastases proved effective. The patient survived for 3 years and 2 months.

[A case of splenic abscess in which percutaneous abscess drainage was an effective].

An eighty-six-year-old man was admitted to our hospital for bacterial septic shock due to splenic abscess. He had undergone percutaneous coronary intervention 3 weeks earlier. Percutaneous splenic abscess drainage was urgently performed under ultrasonography, and then the general state of the patient rapidly improved. Staphylococcus hemolyticus was isolated from the splenic abscess. We reported that percutaneous catheter drainage was effective for splenic abscess.

Aberrant expression of selenoproteins in the progression of colorectal cancer.

Since damage to DNA and other cellular molecules by reactive oxygen species ranks high as a major culprit in the onset and development of colorectal cancer, the aim of the present study is to clarify the role of antioxidant seleonoproteins including glutathione peroxidase (GPx), thioredoxin reductase (TXR) and selenoprotein P (SePP), and the effect of oxidative stress on the progression of colorectal cancer. Expression of 14 oxidative stress-related molecules in both tumorous and non-tumorous tissues in 41 patients was examined by immunohistochemistry and Western blot analysis. Expression levels of proteins modified by 4-hydroxy-2-nonenal (4-HNE), malonyldialdehyde (MDA) and 4-hydroxy-2-hexenal (4-HHE), and the positive rate of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in tumorous tissues were much higher than those in non-tumorous tissues. Glutathione (GSH) content in tumor tissues was much lower than that in non-tumorous tissues. Expression level of selenoproteins such as GPx-1, GPx-3, and SePP, which are rapidly degraded during selenium deprivation, was significantly decreased in tumorous tissues, whereas that of GPx-2, which is resistant to selenium deprivation, was increased. Expression of SePP was decreased at stage III and IV, compared to that of stage II. These data suggest that contrasting expression pattern of the antioxidant selenoproteins plays an important role in the progression of colorectal cancer.

[Two cases of primary T cell lymphoma of the small intestine diagnosed by perforated peritonitis].

We encountered 2 cases (a 28-year-old man and a 63-year-old woman) of primary T cell lymphoma of the small intestine diagnosed by perforated peritonitis. T cell lymphoma perforates the small intestine more easily than B cell lymphoma, because T cell lymphoma infiltrates the intestinal tract wall, and forms an ulcerative tumor.

Naked gene therapy of hepatocyte growth factor for dextran sulfate sodium-induced colitis in mice.

Ulcerative colitis (UC) is progressive and relapsing disease. To explore the therapeutic effects of naked gene therapy of hepatocyte growth factor (HGF) on UC, the SRalpha promoter driving HGF gene was intrarectally administered to the mice in which colitis was induced by dextran sulfate sodium (DSS). Expression of the transgene was seen in surface epithelium, lamina propria, and muscularis mucosae. The HGF-treated mice showed reduced colonic mucosal damage and increased body weights, compared with control mice (P < 0.01 and P < 0.05, respectively). The HGF-treated mice displayed increased number of PCNA-positive cells and decreased number of apoptotic cells than in control mice (P < 0.01, each). Phosphorylated AKT was dramatically increased after HGF gene administration, however, phosphorylated ERK1/2 was not altered. Microarray analysis revealed that HGF induced expression of proliferation- and apoptosis-associated genes. These data suggest that naked HGF gene delivery causes therapeutic effects through regulation of many downstream genes.

Therapeutic effect of adenoviral-mediated hepatocyte growth factor gene administration on TNBS-induced colitis in mice.

Inflammatory bowel disease is incurable and relapsing disease. In order to clarify the effect of HGF gene therapy for inflammatory bowel disease, the adenoviral-mediated HGF gene was intrarectally administered into TNBS-colitis-induced Balb/c mice. Adenoviral-mediated gene delivery targetted its expression mainly to intestinal epithelial cells. Mucosal damage of HGF-treated intestine was significantly improved, and compared with LacZ-treated and saline administered mice (P<0.05, each). The mice treated with intrarectal administration of pAxCAHGF showed an increased average of body weight in comparison with that of pAxCALacZ-treated and saline-treated mice (P<0.05, each). The PCNA-positive cells in pAxCALacZ-treated mice were 44.7+/-4.9%, 51.7+/-6.6%, and 53.9+/-4.5% at 10, 15, and 21 days after TNBS administration, however those in pAxCAHGF-treated mice were increased to 74.3+/-5.1%, 67.1+/-2.6%, and 69.2+/-4.6% (P<0.05, each). The TUNEL-positive cells in pAxCALacZ-treated mice were 13.3+/-5.2%, 11.5+/-2.1%, and 7.2+/-5.2%, respectively. However, those in pAxCAHGF-treated mice at 10, 15, and 21 days were significantly decreased to 5.4+/-1.8%, 3.8+/-1.3%, and 5.7+/-2.8% (P<0.05, respectively). Expression of ERK1/2 was stronger in pAxCAHGF mice than in pAxCALacZ. These data suggest that adenoviral-mediated HGF gene therapy via an intrarectal route is a promising therapy for inflammatory bowel disease.

Analyses to clarify rich fractions in hepatic progenitor cells from human umbilical cord blood and cell fusion.

Umbilical cord blood (UCB) is a source of hematopoietic stem cells and other stem cells, and human UCB cells have been reported to contain transplantable hepatic progenitor cells. However, the fractions of UCB cells in which hepatic progenitor cells are rich remain to be clarified. In the present study, first, the fractionated cells by CD34, CD38, and c-kit were transplanted via portal vein of NOD/SCID mice, and albumin mRNA expression was examined in livers at 1 and 3 months posttransplantation. At 1 and 3 months, albumin mRNA expression in CD34+UCB cells-transplanted livers was higher than that in CD34- cells-transplanted livers. Albumin mRNA expression in CD34+CD38+ cells-transplanted livers was higher than that in CD34+CD38- cells-transplanted [corrected] liver at 1 month. However, it was much higher [corrected] in CD34+CD38- cell-transplanted livers at 3 months. Similar expression of albumin mRNA was obtained between CD34+CD38+c-kit+ cells- and CD34+CD38-c-kit- cells-transplanted livers, and between CD34+CD38-c-kit+ cells- and CD34+CD38-c-kit- cells-transplanted livers, respectively. Second, fluorescence in situ hybridization and immunohistochemistry were performed to examine whether UCB cells really transdifferentiated into hepatocytes or they only fused with mouse hepatocytes. In mouse liver sections, of 1.2% cells which had human chromosomes, 0.9% cells were due to cell fusion, whereas 0.3% cells were transdifferentiated into human hepatocytes. These results suggest that CD34+UCB cells are rich fractions in hepatic progenitor cells, and that transdifferentiation from UCB cells into hepatocytes as well as cell fusion simultaneously occur in this situation.

Retinoic acid receptor alpha dominant negative form causes steatohepatitis and liver tumors in transgenic mice.

Although attention has focused on the chemopreventive action of retinoic acid (RA) in hepatocarcinogenesis, the functional role of RA in the liver has yet to be clarified. To explore the role of RA in the liver, we developed transgenic mice expressing RA receptor (RAR) alpha- dominant negative form in hepatocytes using albumin promoter and enhancer. At 4 months of age, the RAR alpha- dominant negative form transgenic mice developed microvesicular steatosis and spotty focal necrosis. Mitochondrial beta-oxidation activity of fatty acids and expression of its related enzymes, including VLCAD, LCAD, and HCD, were down-regulated; on the other hand, peroxisomal beta-oxidation and its related enzymes, including AOX and BFE, were up-regulated. Expression of cytochrome p4504a10, cytochrome p4504a12, and cytochrome p4504a14 was increased, suggesting that omega-oxidation of fatty acids in microsomes was accelerated. In addition, formation of H2O2 and 8-hydroxy-2'-deoxyguanosine was increased. After 12 months of age, these mice developed hepatocellular carcinoma and adenoma of the liver. The incidence of tumor formation increased with age. Expression of beta-catenin and cyclin D1 was enhanced and the TCF-4/beta-catenin complex was increased, whereas the RAR alpha/ beta-catenin complex was decreased. Feeding on a high-RA diet reversed histological and biochemical abnormalities and inhibited the occurrence of liver tumors. These results suggest that hepatic loss of RA function leads to the development of steatohepatitis and liver tumors. In conclusion, RA plays an important role in preventing hepatocarcinogenesis in association with fatty acid metabolism and Wnt signaling.