Gastroenterologia Japonica

REACH evaluated ramucirumab in the second-line treatment of patients with advanced hepatocellular carcinoma. In the intent-to-treat population (n = 565), a significant improvement in overall survival (OS) was not observed. In patients with an elevated baseline α-fetoprotein (AFP) level (400 ng/mL or greater), an improvement in OS was demonstrated. An analysis of the Japanese patients in REACH was performed. An analysis was performed with the subset of the intent-to-treat population enrolled in Japan (n = 93). The median OS was 12.9 months for the ramucirumab arm (n = 45) and 8.0 months for the placebo arm (n = 48) [hazard ratio (HR) 0.621 (95 % confidence interval (CI) 0.391–0.986); P = 0.0416]. The median progression-free survival was 4.1 months for the ramucirumab arm and 1.7 months for the placebo arm [HR 0.449 (95 % CI 0.285–0.706); P = 0.0004]. The objective response rates were 11 % for the ramucirumab arm and 2 % for the placebo arm (P = 0.0817). The grade 3 or higher treatment-emergent adverse events occurring in more than 5 % of patients with a higher incidence for the ramucirumab arm (n = 44) than for the placebo arm (n = 47) were ascites (7% vs 2 %), hypertension (7 % vs 2 %), and cholangitis (7 % vs 0 %). In patients with a baseline AFP level of 400 ng/mL or greater, the median OS was 12.9 months for the ramucirumab arm (n = 20) and 4.3 months for the placebo arm (n = 22) [HR 0.464 (95 % CI 0.232–0.926); P = 0.0263]. In the Japanese patients in REACH, ramucirumab treatment improved OS, including in patients with a baseline AFP level of 400 ng/mL or greater; improvements in progression-free survival and objective response rate were also demonstrated. The safety profile of ramucirumab was acceptable and well tolerated in Japanese patients. ClinicalTrials.gov identifier NCT01140347.

The major difficulty of mapping parallel gene expression obtained from solid tumors is mainly due to contaminating cells. In this study, by applying a strategy of parallel gene expression at a cell-cluster or colony level, we have identified the gene expression pattern of T cells within tumor-infiltrating lymphocytes (TILs) obtained from two liver cancer patients. Methods. Here a new method was utilized to analyze the parallel gene expression. By using bioinformatics analysis, the data were also compared with T-cell gene expression present in UniGene. Results. Our results demonstrated that 18 genes in specimen A and 13 genes in specimen B were highly expressed after the removal of a nonspecific TIL cDNA library, by pairing gene hybridization; the genes were expressed in CD3+ cells from peripheral blood mononuclear cells (PBMC). By using BlastN search, 17 of the 18, and 12 of the 13 sequences were exhibited, respectively, in Homo sapiens, with a range of BlastN E values of 0 to 4 × 10−13. The LocusLink distribution in chromosomes obtained from both specimens was not significantly different; 17 of 19 putative genes (both specimen A and specimen B) were observed in the UniGene cluster in Homo sapiens, except for dihydropyrimidinase-related protein-3 and diacyglycerol kinase alpha. Interestingly, only 4 of 19 (21%) putative genes were displayed in the T-cell UniGene database (i.e., LD-78 in Hs. 73817, IL-8 in Hs. 624, TRAIL in Hs. 83429, and Fas ligand in Hs. 2007). Conclusions. By comparison with the reported data and UniGene, the parallel gene expression of T cells obtained from TIL can provide essential new insights into T-cell activity, T-cell extravasation into tumor tissues, and T-cell cytotoxicity against tumor cells.

Pancreatic carcinomas have a high incidence of Ki-ras mutations, and the genetic change is thought to occur at an early stage in the carcinogenesis. The aim of this study was to evaluate the usefulness of detecting genetic mutations in pure pancreatic juice (PPJ). DNA was extracted from tissue specimens of pancreatic carcinomas and from cells in PPJ, and subjected to polymerase chain reaction-single-strand conformation polymorphism analysis. Two types of mobility shifts that indicate Ki-ras mutations were observed in 13 of the 20 (65%) tissue specimens obtained by operation or autopsy. Ten of 15 specimens (67%) of PPJ collected from patients with pancreatic carcinomas showed two types of mobility shifts. Conventional imaging techniques did not show two in 10 of these patients. PPJ from patients with non-cancerous pancreatic diseases showed no Ki-ras mutations. The p53 tumor suppressor gene, examined by PCR-SSCP analysis, was mutated in 8 of the 20 tissue specimens obtained by operation or autopsy (40%). The detection of Ki-ras and p53 mutations in PPJ could be useful for the early diagnosis of pancreatic carcinomas, especially for neoplastic lesions of the intraductal type.

The present study was conducted to determine whether the leucocyte adherence inhibition (LAI) assay was dependent on cell-mediated immunity and whether it was of potential use in diagnosis of pancreatic cancer. The LAI response was significantly positive in 15 PPD skin-test positive individuals but it was abated by pretreatment of sensitized mononuclear cells with anti-T cell antibody (OKT3) or by depletion of monocytes. Therefore, the LAI assay is probably related to cell-mediated immunity. The LAI assay was positive in 13 of 16 patients with pancreatic cancer using pancreatic cancer extract; however, a positive reaction was not found in 11 cases of chronic pancreatitis and 10 cases of hepatocellular carcinoma. Thus, the LAI assay appears rather specific. Mononuclear cells of pancreatic and gastric cancer patients showed LAI reactivity to autologous tumor extracts.

We aimed to determine the incidence and causative factors of reflux esophagitis following Helicobacter pylori eradication in Japanese patients. In patients in whom reflux esophagitis could not be detected endoscopically, we conducted an annual follow-up observation in 326 H. pylori-cured patients, 199 H. pylori-positive patients, and 151 H. pylori-negative patients, to study the incidence and causative factors of reflux esophagitis. Development of reflux esophagitis was observed in 74 (22.7%) of the H. pylori-cured patients during a median follow-up period of 6.0 years, in 16 (8.0%) of the H. pylori-positive patients during a median follow-up period of 5.0 years, and in 29 (19.2%) of the H. pylori-negative patients during a median follow-up period of 5.4 years. The results, after correction for sex and age, showed that H. pylori-cured patients had a significantly higher risk of reflux esophagitis than H. pylori-positive patients (risk ratio, 2.43; P < 0.01), but their risk did not differ from that in the H. pylori-negative patients. It was also shown that hiatal hernia (risk ratio, 4.01; P < 0.01) and smoking history (risk ratio, 1.77; P < 0.05) were significant risk factors for the development of reflux esophagitis. With regard to the development of reflux esophagitis following H. pylori eradiation therapy, we observed that the frequency was higher in H. pylori-cured patients than in H. pylori-positive patients, but the frequency in H. pylori-cured patients and H. pylori-negative patients was the same. We elucidated that hiatal hernia and smoking history are important risk factors for reflux esophagitis.