[A case report of adult-onset IgA vasculitis with repeated migrating abdominal lesions and manifestations].

A 68-year-old woman was referred to our hospital due to widespread purpura on her legs. A diagnosis of IgA vasculitis was made based on the findings of a skin biopsy. However, after being admitted to our hospital, abdominal pain and lower gastrointestinal hemorrhaging developed. The purpura disappeared gradually, whereas the abdominal pain migrated and persisted. Treatment with prednisolone was initiated, and the clinical course improved temporarily. However, her severe abdominal symptoms recurred while, in addition, the intestinal tract lesions migrated after the prednisolone dosage was tapered. Therefore, intravenous high-dose methylprednisolone was administered followed by oral steroids. The dose was thereafter carefully tapered, and the steroid dose reduction was successful with this treatment. We herein report the clinical course of the case along with a review of the relevant literature.

Helicobacter pylori eradication improves gastric atrophy and intestinal metaplasia in long-term observation.

BACKGROUND AND AIM: Helicobacter pylori has been shown to cause atrophic gastritis and intestinal metaplasia (IM), both of which are precancerous lesions. To clarify the mechanism by which H. pylori eradication prevents gastric cancer, we monitored atrophy and IM improvement in gastric mucosa over a long period after H. pylori eradication. METHODS: We monitored 118 patients (72 males, 46 females; mean age 61.3 ± 5.1 years) for a mean of 8.6 years (range 5-13) after successful H. pylori eradication. Biopsy specimens were taken from the greater curvatures of the antrum (A2) and the corpus (B2). RESULTS: Atrophy was significantly decreased in patients with successful H. pylori eradication, both at A2 (from 1.60 ± 0.09 to 1.02 ± 0.08; p < 0.001) and B2 (from 0.71 ± 0.10 to 0.02 ± 0.02; p < 0.001), and IM score was significantly decreased at B2 (from 0.17 ± 0.12 to 0.00 ± 0.00; p < 0.05), but not at A2 (from 0.60 ± 0.11 to 0.43 ± 0.09; p = NS). In patients without successful eradication, however, there were no differences in scores over time. Before eradication, IM score was significantly higher in males than in females, both at A2 (0.81 ± 0.12 vs. 0.25 ± 0.10; p < 0.05) and B2 (0.32 ± 0.08 vs. 0.07 ± 0.04; p < 0.05). CONCLUSION: We were able to monitor the gastric mucosa for a mean of 8.6 years after H. pylori eradication, the longest period reported to date. Significant improvements in gastric atrophy and IM after H. pylori eradication may decrease the risk of gastric cancer.

Endoscopic Removal of Multiple Ingested Cylindrical Batteries.

Button battery ingestion accidents have been reported in multiple previous reports. However, ingestion of cylindrical-type batteries is significant less described in the literature. Cylindrical batteries can reportedly cause corrosive damage to the gastrointestinal mucosa after long-term retention, leading to ulceration and perforation. Here, we present a case of endoscopic removal of eight AA batteries that had been ingested and caused corrosive changes in the gastrointestinal mucosa. A 45-year-old man with mental retardation was brought to our hospital due to the suspicion of cylindrical battery ingestion. A plain abdominal x-ray revealed a total of eight cylindrical batteries. Esophagogastroduodenoscopy was performed approximately 24 hours after ingestion, and four AA batteries were removed using a polypectomy snare. The remaining four batteries were followed up and removed under colonoscopy after confirming that they had reached the rectum. Leaked components of retained cylindrical batteries can cause chemical mucosal damage in the gastrointestinal tract. Therefore, early extraction should be considered in case of cylindrical battery ingestion. On the other hand, when the cylindrical battery has passed the pyloric ring, conservative management with close monitoring is acceptable if there are no clinical symptoms. Additionally, a polypectomy snare is useful in the extraction of ingested cylindrical batteries.

Impact of Helicobacter pylori CagA diversity on gastric mucosal damage: an immunohistochemical study of East-Asian-type CagA.

BACKGROUND AND AIMS: Recently, we successfully produced an anti-East-Asian-type CagA-specific antibody called α-EAS Ab, which is specifically immunoreactive only with East-Asian-type CagA but not Western-type CagA. In this study, the correlations between Helicobacter pylori CagA protein diversity and gastric mucosal condition was investigated using immunohistochemical staining with α-EAS Ab in Japan. METHODS: There were 254 H. pylori-positive patients enrolled in this study. α-EAS Ab was used to determine the CagA phenotype instead of cagA sequencing, and, moreover, the histological findings and endoscopic gastric mucosal condition were evaluated according to the updated Sydney System and the Kimura-Takemoto classification system, respectively. RESULTS: A total of 224 (88.2%) of the patients were immunoreactive for α-EAS Ab. The remaining 30 (11.8%) were negative for α-EAS Ab, suggesting that they were infected with either Western-type CagA or CagA-negative strains (i.e. non-East-Asian-type CagA strains). The grades of activity of gastritis, mucosal atrophy and intestinal metaplasia according to the updated Sydney System were significantly higher in patients infected with East-Asian-type CagA strains than those infected with non-East-Asian-type CagA strains. The grade of endoscopic gastric mucosal atrophy evaluated using the Kimura-Takemoto classification system was similar. All 28 strains isolated from patients with gastric cancer possessed the East-Asian-type CagA. CONCLUSIONS: Infection with East-Asian-type CagA H. pylori was more closely associated with gastric mucosal atrophy and gastric cancer than infection with non-East-Asian-type CagA H. pylori. The efficiency of immunohistochemical analysis for CagA should be equivalent to that of cagA sequencing.

Monomorphic epitheliotropic intestinal T-cell lymphoma presenting as melena with long-term survival: A case report and review of literature.

BACKGROUND: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare primary intestinal T-cell lymphoma, previously known as enteropathy-associated T-cell lymphoma type II. MEITL is an aggressive T-cell lymphoma with a poor prognosis and high mortality rate. The known major complications of MEITL are intestinal perforation and obstruction. Here, we present a case of MEITL that was diagnosed following upper gastrointestinal bleeding from an ulcerative duodenal lesion, with recurrence-free survival for 5 years. CASE SUMMARY: A 68-year-old female was admitted to our hospital with melena and mild anemia. An urgent esophagogastroduodenoscopy (EGD) revealed bleeding from an ulcerative lesion in the transverse part of the duodenum, for which hemostatic treatment was performed. MEITL was diagnosed following repeated biopsies of the lesion, and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy was administered. She achieved complete remission after eight full cycles of CHOP therapy. At the last follow-up examination, EGD revealed a scarred ulcer and 18Fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography showed no abnormal FDG accumulation. The patient has been in complete remission for 68 mo after initial diagnosis. CONCLUSION: To rule out MEITL, it is important to carefully perform histological examination when bleeding from a duodenal ulcer is observed.

Evaluation of a new tumor necrosis factor-alpha-inducing membrane protein of Helicobacter pylori as a prophylactic vaccine antigen.

BACKGROUND: Tumor necrosis factor (TNF)-alpha-inducing protein (Tip alpha) is a newly identified carcinogenic factor present in Helicobacter pylori. Tip alpha has the unique function of inducing TNF-alpha production by gastric cells in vitro and is assumed to be related with the development of gastritis and gastric cancer. We investigated the effects of vaccination with Tip alpha against H. pylori infection and analyzed the immune responses. METHODS: C57BL/6 mice were immunized via the intranasal route with CpG, recombinant Tip alpha + CpG, and recombinant del-Tip alpha (a mutant of Tip alpha) + CpG. Eight weeks after the mice were infected with H. pylori (5 x 10(7) CFU), the number of colonizing bacteria in the stomach was calculated, and the histological severity of gastritis was evaluated. Levels of Tip alpha-specific IgG and IgA antibodies in mouse serum were measured by an enzyme-linked immunosorbent assay (ELISA). Local production of cytokines including Interleukin (IL)-10, TNF-alpha and Interferon (IFN)-gamma in gastric mucosa was also measured by real time-PCR. RESULTS: Levels of Tip alpha-specific antibodies were significantly higher in Tip alpha-immunized and del-Tip alpha-immunized mice than in the infection control group. The numbers of colonizing bacteria were significantly reduced in Tip alpha-immunized mice (4.29 x 10(5) CFU/g) and del-Tip alpha immunized mice (2.5 x 10(5 )CFU/g) compared with infection control mice (5.7 x 10(6) CFU/g). The levels of IFN-gamma and IL-10 were significantly higher in del-Tip alpha-immunized mice than the infection control group. CONCLUSION: Vaccinations with Tip alpha and del-Tip alpha were effective against H. pylori infection. The inhibition of H. pylori colonization is associated mainly with Th1 cell-mediated immunity.

Helicobacter pylori and NSAID-induced gastric ulcer in a Japanese population.

A recent meta-analysis by Huang et al. clarified that Helicobacter pylori infection and nonsteroidal antiinflammatory drugs (NSAIDs) are important factors for peptic ulcer. The results showed that the risk for ulcer in NSAID(+)/H. pylori(+) patients was 61.1 fold higher when compared with NSAID(-)/H. pylori(-) patients. Some gastric ulcers detected in patients on NSAID therapy may actually be caused by H. pylori, but it is difficult to differentiate NSAID-induced gastric ulcer from H. pylori-induced gastric ulcer. Several studies have investigated the effects of H. pylori eradication on ulcer healing. One study reported that H. pylori eradication actually lowered the healing rate of gastric ulcers. Because there have been no studies finding that H. pylori eradication facilitates healing, H. pylori eradication is not recommended for NSAID users. Concerning the efficacy of H. pylori eradication in the prevention of NSAID-induced gastric ulcer, a meta-analysis concluded that among all patients on NSAID therapy, H. pylori eradication lowered the prevalence of ulcer, which was particularly marked in NSAID-naïve patients. When compared with those of proton pump inhibitors (PPIs), the preventative effects of H. pylori eradication were inferior. In Japan, national health insurance does not cover procedures that prevent or lower the risk for NSAID-induced ulcer. When administering NSAID to patients with risk factors, it is desirable to administer antiulcer agents.

Commensal microbiota contributes to chronic endocarditis in TAX1BP1 deficient mice.

Tax1-binding protein 1 (Tax1bp1) negatively regulates NF-κB by editing the ubiquitylation of target molecules by its catalytic partner A20. Genetically engineered TAX1BP1-deficient (KO) mice develop age-dependent inflammatory constitutions in multiple organs manifested as valvulitis or dermatitis and succumb to premature death. Laser capture dissection and gene expression microarray analysis on the mitral valves of TAX1BP1-KO mice (8 and 16 week old) revealed 588 gene transcription alterations from the wild type. SAA3 (serum amyloid A3), CHI3L1, HP, IL1B and SPP1/OPN were induced 1,180-, 361-, 187-, 122- and 101-fold respectively. WIF1 (Wnt inhibitory factor 1) exhibited 11-fold reduction. Intense Saa3 staining and significant I-κBα reduction were reconfirmed and massive infiltration of inflammatory lymphocytes and edema formation were seen in the area. Antibiotics-induced 'germ free' status or the additional MyD88 deficiency significantly ameliorated TAX1BP1-KO mice's inflammatory lesions. These pathological conditions, as we named 'pseudo-infective endocarditis' were boosted by the commensal microbiota who are usually harmless by their nature. This experimental outcome raises a novel mechanistic linkage between endothelial inflammation caused by the ubiquitin remodeling immune regulators and fatal cardiac dysfunction.

Aspirin-induced small bowel injuries and the preventive effect of rebamipide.

AIM: To evaluate the influence of taking low-dose aspirin for 4 wk on small intestinal complications and to examine the preventive effect of rebamipide. METHODS: This study was conducted as a single-center, randomized, double-blind, cross-over, placebo-controlled study. Eleven healthy male subjects were enrolled. Each subject underwent video capsule endoscopy after 1 and 4 wk of taking aspirin and omeprazole, along with either rebamipide or placebo therapy. The primary endpoint was to evaluate small bowel damage in healthy subjects before and after taking low-dose aspirin for 4 wk. RESULTS: The number of subjects with mucosal breaks (defined as multiple erosions and/or ulcers) were 1 at 1 wk and 1 at 4 wk on the jejunum, and 6 at 1 wk (P = 0.0061) and 7 at 4 wk on the ileum (P = 0.0019). Rebamipide significantly prevented mucosal breaks on the ileum compared with the placebo group (P = 0.0173 at 1 wk and P = 0.0266 at 4 wk). CONCLUSION: Longer-term, low-dose aspirin administration induced damage in the small bowel. Rebamipide prevented this damage, and may be a candidate drug for treating aspirin-induced small bowel complications.

Comparison of amoxicillin-metronidazole plus famotidine or lansoprazole for amoxicillin-clarithromycin-proton pump inhibitor treatment failures for Helicobacter pylori infection.

BACKGROUND: Proton pump inhibitor-amoxicillin-metronidazole is recommended as second-line Helicobacter pylori therapy in Japan. The authors assessed the efficacy and safety of second-line eradication using the H2-receptor antagonist famotidine as a substitute for proton pump inhibitor. MATERIALS AND METHODS: Sixty-one patients who failed in first-line H. pylori eradication using proton pump inhibitor-clarithromycin-amoxicillin were randomly assigned to either second-line therapy including metronidazole: a 7-day course of lansoprazole 30 mg, amoxicillin 750 mg, and metronidazole 250 mg, b.i.d. (lansoprazole group); or a 7-day course of famotidine 40 mg, amoxicillin 750 mg, and metronidazole 250 mg, b.i.d. (famotidine group). Eradication was assessed for each group at least 4 weeks after completing eradication therapy. Drug susceptibility test was performed using 57 strains in pretreatment to clarithromycin, metronidazole, and amoxicillin. RESULTS: Prior to second-line H. pylori eradication, the rate of resistance to clarithromycin was high at 84% (48/57). Similarly, resistance to metronidazole was low at 5.3% (3/57); however, no amoxicillin-resistant strains were found. The eradication rates for both lansoprazole and famotidine treatment groups were high at 97% (29/30) and 94% (29/31), respectively. CONCLUSIONS: Famotidine treatment including metronidazole-amoxicillin as second-line therapy provided a high eradication rate similar to lansoprazole therapy. Famotidine is therefore expected to serve as a useful H. pylori eradication regimen in patients with proton pump inhibitor allergy, an economic benefit in terms of reduced health-care costs is also anticipated.