Hiroko Nebiki

Effects of zincl-carnosine on gastric mucosal and cell damage caused by ethanol in rats

The effects of zincl-carnosine on ethanol-induced damage and the correlation of these effects with endogenous prostaglandin E2 were evaluated in rat gastric mucosain vivo andin vivo. When given either intragastrically or intraperitoneally, zincl-carnosine (10 or 30 mg/kg) prevented gross visible damage to gastric mucosa caused by ethanol without affecting the mucosal prostaglandin E2 level. This protective effect of zincl-carnosine was not inhibited by indomethacin. Histological assessment showed that zincl-carnosine inhibited deep mucosal necrosis, as did 16,16-dimethyl-prostaglandin E2. Zincl-carnosine (10−6 or 10−5 M) inhibited the damage caused by ethanol to gastric cells isolated from rat gastric mucosain vivo; this effect was not inhibited by indomethacin. The results suggested that zincl-carnosine protects the gastric mucosa and enhances cellular resistance to ethanol without the mediation of endogenous prostaglandins.

Spontaneous Regression of Hepatocellular Carcinoma: Report of a Case

A spontaneous regression of hepatocellular carcinoma is an extremely rare phenomenon. A 69-year-old Japanese man with hepatitis C virus-related chronic hepatitis presented with a liver tumor. We diagnosed the tumor to be hepatocellular carcinoma in the course of spontaneous regression, by imaging studies and changes in the tumor markers. Because the possible presence of viable cancer cells could not be ruled out, we recommended surgery. He refused all treatments at first, but finally agreed to undergo surgery about 10 months after presentation. A hepatectomy was performed. Histologically, no viable tumor cells were found. In our case, the vascularity of the tumor according to the imaging findings was followed up during the clinical course. The patient is now doing well and without any evidence of recurrence at 37 months after surgery.

Cap polyposis cured by Helicobacter pylori eradication therapy.

Helicobacter pylori eradication. A 63-year-old man was diagnosed as having cap polyposis with mucoid stool, diarrhea, and bleeding on defecation. Following 5 weeks of total parenteral nutrition, his symptoms and hypoproteinemia improved and he was discharged, although follow-up colonoscopic findings revealed no improvement. Subsequent gastroscopy revealed diffusely erosive polyps with cap-like “fur” from the angle to the antrum of the stomach, similar to the lesions observed in the colon. Because H. pylori infection was demonstrated in the stomach, eradication therapy was administered. After this treatment, his symptoms immediately disappeared, and the polypoid lesions in the colon and stomach had completely disappeared 8 months later. Because there have been no previous reports of a relationship between H. pylori and cap polyposis, this case is of great interest.

Sleep Dysfunction in Japanese Patients with Gastroesophageal Reflux Disease: Prevalence, Risk Factors, and Efficacy of Rabeprazole

Background and Aim: Several studies performed in Western countries demonstrate the association between sleep dysfunction and gastroesophageal reflux disease (GERD), especially when nighttime heartburn is present. The purpose of this study was to examine the prevalence and risk factors of sleep dysfunction, and the effect of rabeprazole on reflux symptoms and sleep dysfunction in Japanese GERD patients. Methods: A total of 134 GERD patients, including 82 patients with non-erosive reflux disease (NERD), were enrolled. Patients received rabeprazole 10 mg daily for 8 weeks. Patients were asked to complete both a frequency scale for symptoms of GERD (FSSG) questionnaire and a Pittsburgh Sleep Quality Index (PSQI) questionnaire at baseline and 8 weeks after treatment. Results: Sleep dysfunction defined as a PSQI score >5.5 was found in 70 (52.2%) of the GERD patients. NERD was significantly associated with sleep dysfunction compared to erosive reflux disease (OR 2.18, 95% CI 1.05–4.53). However, other factors, including nighttime heartburn, were not associated with sleep dysfunction. Rabeprazole treatment significantly decreased both the FSSG and the PSQI score. Conclusion: The prevalence of sleep dysfunction was high among GERD patients. NERD was identified as a risk factor for sleep dysfunction. Use of a proton-pump inhibitor led to an effective decrease in sleep dysfunction. These results suggest a different pathogenesis of sleep dysfunction in Japanese GERD patients compared to GERD patients in Western countries. However, acid plays an important role in sleep dysfunction in all patients with GERD.

Quality of ulcer healing influences the relapse of gastric ulcers in humans

The usefulness of dye‐contrast endoscopy for the evaluation of the quality of gastric ulcer healing and the prediction of relapse was investigated. Sixty consenting patients whose ulcers healed during 3 months of treatment underwent endoscopy for the identification of the pattern of mucosal regeneration. Patients were monitored for relapses for up to 18 months after antiulcer therapy had ended. The pattern of regeneration was flat in 24 patients, nodular in 25 and intermediate in 11. Internal hypoechoic areas seen by endoscopic ultrasonography were less common and histological maturity was better in the patient group with the flat pattern compared with the patient group with the nodular pattern of mucosal regeneration. Prostaglandin E, synthesis was highest in the group with the flat pattern of mucosal regeneration and the relapse rate was lowest in this group. We conclude that the evaluation of the quality of ulcer healing is possible and that findings in individuals may aid the prediction of relapse for particular patients.

Gastric Cytoprotection by Tetraprenylacetone in Human Subjects

We assessed the inhibition by tetraprenylacetone (TPA) of gastric mucosal damage caused by ethanol in human subjects. Seventeen healthy volunteers were given either TPA (a 50-mg capsule) or a placebo 3 times daily for 5 days. Then, 20 ml of 70% ethanol were sprayed onto the gastric antrum and 15 min later, visible mucosal lesions were evaluated with an endoscope, and biopsy specimens were taken from mucosa that looked normal but had been sprayed with ethanol. The specimens were observed by light microscopy and scanning electron microscopy. The gross mucosal damage was significantly less (p less than 0.05) in the subjects given TPA than in those given the placebo. Hyperemia and hemorrhage in the mucosa and surface epithelial damage were also significantly less (p less than 0.05) in the subjects given TPA. The results suggested that TPA protects the gastric mucosa from damage by ethanol as judged not only by the gross appearance of the mucosa but also by microscopic observation.

Regression of gastric MALT lymphoma after unsuccessful anti-H. pylori therapy

rates vary more than 50-fold worldwide (3). Variation of this magnitude, with the highest rates in developed countries, suggests that risk is principally determined by exposure to carcinogenic agents moderated by protective factors. For colon cancer, heterocyclic amines formed in the charring of meat and fish products may represent an important causal agent with physical activity (4) and cereals protective.

Protection of gastric surface epithelial cells of rats by 16,16-dimethyl prostaglandin E2 and sofalcone, a synthetic flavonoid derivative of sophoradin, against ethanol

We studied the effects of 16,16-dimethyl prostaglandin E2 (dm-PGE2) and sofalcone, a new antiulcer agent developed in Japan, on ethanol damage to isolated surface epithelial cells (SEC) in vitro and gastric mucosa of rats in vivo. Rats were given 5 micrograms/kg dm-PGE2, 30, 100, or 300 mg/kg sofalcone, or the vehicle, intraperitoneally. In the in vitro study, damage of the SEC isolated from rats given dm-PGE2 or sofalcone was significantly less after exposure to 15% ethanol than for the SEC from the control rats. In the in vivo study, the 15% ethanol did not induce gross visible damage, but did cause surface epithelial damage in the control rats as judged by scanning electron microscopy. This damage was inhibited by dm-PGE2 or sofalcone. Damage from absolute ethanol was inhibited by both of the agents as judged by the gross appearance, but the surface epithelium was damaged in all rats. We concluded that dm-PGE2 and sofalcone protect gastric mucosa from gross damage caused by absolute ethanol, and protect SEC both in vivo and in vitro from being damaged by ethanol when the concentration of ethanol is 15%.

Multicenter, randomized, open-label Phase II study comparing S-1 alternate-day oral therapy with the standard daily regimen as a first-line treatment in patients with unresectable advanced pancreatic cancer

PurposeNon-inferiority for overall survival (OS) following alternate-day treatment with the oral anticancer drug S-1 compared with standard daily treatment was assessed in Japanese patients with unresectable advanced pancreatic cancer in a multicenter, randomized, phase II study. This trial was registered at the UMIN Clinical Trials Registry (no. 000008604).MethodsChemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned 2:1 to treatment with alternate-day (twice daily on alternate days from days 1 through 42 of a 42-day cycle) or daily (twice daily on days 1 through 28 of a 42-day cycle) treatment with S-1. The primary endpoint was OS. Secondary endpoints were progression-free survival (PFS), time to treatment failure, response rate, quality of life assessments, and safety.ResultsA total of 190 patients were enrolled, of which 185 were included in the final analysis (alternate-day: 121; daily: 64). Median OS was 9.4 for the alternate-day group and 10.4 months for the daily group [hazard ratio (HR), 1.19; 95% credible interval, 0.86 to 1.64], indicating that non-inferiority of alternate-day treatment to daily treatment was not demonstrated. Median PFS was 3.0 for the alternate-day group and 4.2 months for the daily group (HR, 1.65; 95% credible interval, 1.20–2.29). The incidence of anorexia, fatigue, neutrophils, pigmentation, and pneumonitis was lower in alternate-day treatment compared with daily treatment.ConclusionS-1 for advanced pancreatic cancer should be taken daily as recommended, based on the decreased OS and PFS and marginal improvement in safety observed in the alternate-day group.

The Efficacies and Issues for Endoscopic Assessment of Mucosal Healing in Patients with Crohn’s Disease

Mucosal healing has been a focus of attention as an emerging ideal treatment goal of Crohn’s disease. Endoscopy is the gold standard for evaluating mucosal lesion. Objective precise monitoring, especially for the small bowel, is important for stratifying the treatment strategy. Some limitations and issues for definition of mucosal healing, accessibility of stricture or adhesion, feasible endoscopic score still remain. It is important in clinical practice to identify the appropriate time for intensifying the CD treatment for small ulcerative lesion endoscopically. There are characters for each imaging modality, for instance assessment of intestinal tract wall and extrawall information. The combination with other complementary imaging modalities or biomarkers is useful in optimizing the CD treatment strategy. An appropriate accelerated step-up treatment strategy combined with stratified precise monitoring of the SB should provide optimal prognosis in patients with CD. Endoscopic prediction of long-term prognosis or efficacy of treatment is an important subject for investigation.