Vonoprazan-based triple therapy is non-inferior to susceptibility-guided proton pump inhibitor-based triple therapy for Helicobacter pylori eradication.

BACKGROUND: All Helicobacter pylori-infected patients are recommended for eradication with an appropriate regimen in each geographic area. The choice of the therapy is somewhat dependent on the antimicrobial susceptibility. The rate of clarithromycin resistance has been increasing and is associated with failure; thus, susceptibility testing is recommended before triple therapy with clarithromycin. However, antimicrobial susceptibility testing is not yet clinically available and an alternative newly developed acid inhibitor vonoprazan is used for triple therapy in Japan. The aim of this study was to determine whether vonoprazan-based triple therapy is plausible treatment in H. pylori eradication. METHODS: A retrospective observational study of H. pylori eradication was conducted in a single institute. The patients who requested antimicrobial susceptibility testing were treated with susceptibility-guided proton pump inhibitor-based triple therapy in International University of Health and Welfare Hospital from 2013 to 2016. Other patients were treated with empirical treatment with a proton pump inhibitor. From 2015 to 2016, vonoprazan-based triple treatment (vonoprazan, 20 mg; amoxicillin, 750 mg; and clarithromycin, 200 or 400 mg, b.i.d.) was conducted, and its effectiveness was compared with susceptibility-guided proton pump inhibitor-based triple therapy. We also investigated the improvement in eradication rate when antimicrobial susceptibility testing was performed, and compared the outcomes of vonoprazan-based and proton pump inhibitor-based empirical therapy. RESULTS: A total of 1355 patients who received first-line eradication treatment were enrolled in the present study. The eradication rates of the empirical proton pump inhibitor-based therapy and the vonoprazan-based therapy group in a per-protocol analysis were 86.3% (95% CI 83.8-88.8) and 97.4% (95% CI 95.7-99.1), respectively. In 212 patients who received antimicrobial susceptibility testing, the rate of clarithromycin resistant was 23.5% and the eradication rate in susceptibility-guided treatment was 95.7% (95% CI 92.9-98.4). The difference between susceptibility-guided and vonoprazan-based therapy was - 1.7% (95% CI - 4.9 to 1.5%), and the non-inferiority of vonoprazan-based triple therapy was confirmed. CONCLUSIONS: Vonoprazan-based triple therapy was effective as susceptibility-guided triple therapy for H. pylori eradication. An empirical triple therapy with vonoprazan is preferable even in area with high rates of clarithromycin-resistance. Trial registration The study was retrospectively registered in University Hospital Medical Information Network (UMIN000032351).

Laparoscopy-assisted total gastrectomy for advanced gastric cancer with carcinomatous ascites after S1 plus cisplatin chemotherapy: a case report.

A 29-year-old man with a type 4 tumor, in the lower third of the stomach, and carcinomatous ascites was diagnosed by aspiration cytology of the ascitic fluid. Curative resection was considered impossible, and S1 (120 mg/d) and cisplatin (90 mg/d) were given for 21 days in 1 course. The cancer lesion showed marked remission (partial response), and the ascites completely disappeared after the fourth course. Twenty-five days after completion of the S1 treatment, laparoscopy-assisted total gastrectomy was performed. Histopathological examination showed no remnant cancer cells in the resected specimen and no lymph node metastases. The tumor was replaced with fibrosis having a granulomatous change. The patient's postoperative course was uneventful. The patient was continued with S1 monotherapy after surgery, and no signs of recurrence or metastases have been seen on any examination 12 months after the surgery.

Possibility of preventing colorectal carcinogenesis with probiotics.

BACKGROUND/AIMS: There have been no reports on the relationship between the analyses of the intestinal flora of colorectal cancer patients and colorectal carcinogenesis. In this study we investigated the differences between the intestinal flora of colorectal cancer patients and healthy subjects and assessed the possibility of using probiotics to prevent colorectal carcinogenesis. METHODOLOGY: The subjects were 10 colorectal cancer patients and 20 healthy persons. A stool specimen and peripheral blood specimen were collected from the patients and 10 of the healthy subjects to analyze their intestinal flora and measure natural killer (NK) cell activity and IL-1 beta in their blood. Probiotics (Lactobacillus gasseri OLL2716: LG21) was then administered once daily to 10 of the healthy subjects for 12 weeks. Samples were collected after 4 weeks, 8 weeks, and 12 weeks of administration, and the same examinations were performed. RESULTS: The Lactobacillus detection rate was significantly higher in the healthy group than in the colorectal cancer group, and the total Clostridium perfringens was higher in the colorectal cancer group. The stool pH of the colorectal cancer group indicated alkalosis, and the total amount of short-chain fatty acids in the stools tended to be lower than in the healthy group. After ingestion of the probiotic, the Lactobacillus detection rate increased, a decrease in the total amount of Clostridium perfringens was seen, fecal pH indicated acidosis, synthesis of fecal putrefaction products was inhibited, and an increase in the short-chain fatty acid isobutyric acid was observed. The blood IL-1 beta and NK cell activity values were significantly higher from the 4th week onward than the values before ingestion of probiotics. CONCLUSIONS: A deterioration of the intestinal environment was observed in the colorectal cancer patients in comparison to the healthy controls, and the intestinal environment improved when probiotics was taken. These findings suggest the possibility of preventing colorectal carcinoma with probiotics.

Effects of Lansoprazole on the Lipopolysaccharide-Stimulated Toll-Like Receptor 4 Signal Transduction Systems: A Study Using the 293hTLR4/MD2-CD14 Cells.

The present study was undertaken to evaluate the effects of lansoprazole (LPZ) on lipopolysaccharide (LPS)-stimulated toll-like receptor 4 (TLR4) signal transduction systems using the 293hTLR4/MD2-CD14 cells. The cells were incubated and then divided into the following groups: (a) untreated group, (b) non-LPZ treated (1h) group, (c) LPZ-treated (1h) plus non LPS-stimulated (1h) group, (d) LPZ-treated (1h) plus non LPS-stimulated (6h) group, (e) LPZ-treated (1h) plus LPS-stimulated (1h) group, (f) LPZ-treated (1h) plus LPS-stimulated (6h) group, (g) non LPZ-treated (1h) plus LPS-stimulated (1h) group and (h) non LPZ-treated (1h) plus LPS-stimulated (6h) group. Samples from each group were subjected to western blotting for analysis of IkB phosphorylation, intranuclear transfer of NF-kB, phosphorylation of MAP kinase (MAPK), intranuclear transfer of interferon regulatory factor 5 (IRF5), and expression of suppressor of cytokine signaling-1 (SOCS1). In the LPZ-treated groups, neither phosphorylation of MAPK nor intranuclear transfer of IRF5 was suppressed under stimulation with LPS, and enhanced intranuclear transfer of NF-kB and increased expression of SOCS1 were noted by comparison with the group treated with LPS alone. These results suggest that LPZ stimulates the expression of SOCS1 and regulates protein phosphorylation through its activity on TLR4 signal transduction under LPS stimulation.

[Pre- and probiotics increase host-cell immunological competence, improve bowel movement, and prevent the onset of colon cancer--an analysis based on movements of intestinal microbiota].

The activation of host immunological competence through improvement of the intestinal environment by pre and probiotics has been reported. NK cell activity, the bactericidal phagocytic activities of neutrophils in peripheral blood, and bowel movements and short chain fatty acids (SCFAs) in intestinal microbiota increase after the administration of pre- and probiotics. SCFAs shift to acidosis of the intestinal environment and advance apoptosis. Furthermore, SCFAs promote intestinal peristaltic movements through SCFA receptors such as GPT 41 and GPR43, located in the intestinal epithelium. It is known that the acceleration of intestinal apoptosis prevents the onset of colon cancer. Improvement of the intestinal environment leads to an increase in host-cell immunological competence, bowel movements, and the prevention of colon cancer.

New double-stapling technique for esophagojejunostomy and esophagogastrostomy in gastric cancer surgery, using a peroral intraluminal approach with a digital stapling system.

In the abdominal-transhiatal approach for resection of adenocarcinoma of the cardia or subcardia, and in laparoscopy-assisted total gastrectomy (LATG), the use of a circular stapling device has potential problems with the placement of the purse-string suture and insertion of the anvil of the instrument. We describe a new double-stapling technique for esophagojejunostomy and esophagogastrostomy, using a peroral intraluminal approach with a digital stapling system, a flexible shaft remote-control stapler - the Surg-ASSIST and Power Circular Stapler 21 mm (PCS). The overtube of the flexible shaft of the PCS is prepared with a nylon tie and secured to a nasogastric (NG) tube. The flexible shaft is manually advanced down the esophagus with guidance by pulling the NG tube from the abdominal cavity side. The trocar of the flexible shaft is removed from the stump of the abdominal esophagus and connected to the anvil and they are approximated; the stapler device is then fired to form a double-stapled esophagojejunostomy and esophagogastrostomy. Our peroral intraluminal approach does not require a suturing technique, and it can make anastomosis after resection for carcinoma of the esophagogastric junction and after LATG safe and simple.

Single nucleotide polymorphism typing of the human toll-like receptor 4 gene at the 2-kb upstream region of the 5' untranslated region: New enclosure strategy for the risk grouping of poorly-differentiated gastric adenocarcinoma patients.

To date, no enclosure method for risk grouping patients with poorly-differentiated gastric adenocarcinoma has been identified. We examined the relationship between mutations in toll-like receptor 4 (TLR4) and patients with poorly-differentiated gastric adenocarcinoma. Genomic DNA was extracted from the peripheral blood of 38 patients, 20 with well-differentiated and 18 with poorly-differentiated gastric cancer, from 25 patients with colorectal cancer and from 10 healthy volunteers. The polymorphism of TLR4 up to the 2-kb upstream region of the 5' untranslated region (UTR) was analyzed. The results revealed the presence of single nucleotide polymorphisms (SNPs) only among patients with poorly-differentiated gastric adenocarcinoma. SNPs were found at 3 sites: -2081, -2026 and -1601 in 12, 15 and 15 of the 18 cases of poorly-differentiated gastric adenocarcinoma, respectively. The results of the determination of a consensus among the base sequences of the core promoter, basal promoter and upstream promoter elements reveal that the variant sites were present in the TLR4 mRNA promoter region, suggesting that they were biologically significant variations. Polymorphism analysis of the upstream region of the 5' UTR of TLR4 may be a useful new enclosure strategy for the risk grouping of poorly-differentiated gastric adenocarcinoma patients.

High incidence of Dieulafoy's lesions in upper gastrointestinal bleeding associated with polyarteritis--clinical examination of patients of polyarteritis nodosa with rapidly progressive glomerulonephritis.

BACKGROUND/AIMS: Polyarteritis nodosa (PN) has been classified into polyarteritis (PA) and microscopic polyarteritis (MA) histologically. To clarify of the characteristics of upper gastrointestinal bleeding lesions in PN, we investigated the patients of PN with rapidly progressive glomerulonephritis (RPGN) presenting with upper gastrointestinal bleeding. METHODOLOGY: The subjects of this study were 21 patients of PN with RPGN (PA: 11, MA: 10) who presented with upper gastrointestinal bleeding. The bleeding lesions and their locations were examined endoscopically in the study subjects, and the relationship of the bleeding to the severity of renal failure, the necessity of hemodialysis (HD), presence/ absence of H. pylori infection and the gender of the patients were analyzed. RESULTS: The bleeding lesions were endoscopically identified as esophageal ulcers in 2 cases, gastric ulcers in 15 cases and duodenal ulcers in 4 cases, respectively. In 10 of the 15 cases with gastric ulcers, the ulcer assumed the form of Dieulafoy's lesions affecting the gastric body, and the underlying disease was PA in all the 10 cases. In the remaining 5 cases of gastric ulcers and 2 cases of esophageal ulcer with underlying MA or 4 cases of duodenal ulcers, in whom assumed the bleeding form of oozing from the marginal zone of ulcers. In all of the 4 cases of duodenal ulcers, and the 1 case with underlying PA and the other cases with MA, no correlation was found between the onset of the upper gastrointestinal bleeding and the severity of renal failure or the necessity for HD, presence of H. pylori infection, or the gender of the patients. CONCLUSIONS: Dieulafoy's lesions are the most frequent sources of upper gastrointestinal bleeding in cases of PA.

[Early phase II dose-finding study of exemestane in postmenopausal patients with advanced/recurrent breast cancer].

Exemestane was administered orally to postmenopausal women with advanced/recurrent breast cancer at a dose of 10 mg/day or 25 mg/day once daily for more than 8 weeks in order to evaluate the drug's anti-tumor effects and safety in a dose-finding study. The response rate (CR + PR) in the 10 mg and 25 mg group was 25.0% (8/32) and 31.4% (11/35), respectively, demonstrating no significant differences between the two groups, yet a higher efficacy rate was observed in 25 mg group. The efficacy rate in hormone-treatment-resistant patients within the 10 mg and 25 mg groups was 14.3% (3/21) and 26.1% (6/23), respectively, demonstrating more than a 20% response rate in 25 mg group. Incidences of the adverse events of which relevance to the drug could not be excluded were 30.6% (11/36) in the 10 mg group. 13.9% (5/36) in the 25 mg group and 22.2% (16/72) in the total group. The major adverse events were, hot flashes, numbness of the limbs, nausea, headache etc. Abnormal findings in clinical laboratory tests were as follows: ALP increase; GOT increase; GPT increase; gamma-GTP increase; total cholesterol increase; urinary sediment present. Abnormal findings in endocrine function were as follows: aldosterone decrease; testosterone.cortisol.DHEA-S decrease. But discontinuation due to abnormal laboratory findings was not found. No abnormal findings in physical tests were observed. A significant decrease in plasma estrogen concentration at week 4 was observed in both the 10 mg and 25 mg groups compared with baseline. These low levels were maintained throughout the study period. On the basis of these results, the efficacy of exemestane 25 mg/day was verified to be slightly higher than 10 mg/day. In addition the safety profile had no major adverse events to notice. In these patients with advanced/recurrent breast cancer, 25 mg/day was recommended as the most appropriate dose to be used clinically.