Efficacy of Vonoprazan-Based Triple Therapy for <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Eradication: A Multicenter Study and a Review of the Literature

Background

Eradication therapies for Helicobacter pylori infection are advancing as new acid inhibitory reagents approved. The aim of this study was to assess the efficacy and safety of vonoprazan-based triple treatment.

Materials and Methods

Triple therapy with vonoprazan and two antibiotics (amoxicillin and clarithromycin or metronidazole) received focus in this analysis. We performed a multicenter retrospective study of patients who received vonoprazan-based eradication therapy between February 2015 and February 2016 and conducted a review of the literature.

Results

The eradication rate among the 799 patients in our multicenter study was 94.4% (95% confidence interval [CI] 92.6–96.2%) in the per-protocol analysis for first-line treatment (with vonoprazan 20 mg, amoxicillin 750 mg, and clarithromycin 200 or 400 mg, twice a day for 7 days) and 97.1% (95% CI 93.0–101.1%) for second-line treatment (with vonoprazan 20 mg, amoxicillin 750 mg, and metronidazole 250 mg, twice a day for 7 days). The overall incidence of adverse events was 4.4% in an intention-to-treat analysis with no patients hospitalized. In a literature review, six reports, in which 1380 patients received vonoprazan-based first-line eradication therapy, were included and were all reported by Japanese researchers. The eradication success rates in per-protocol analysis were between 85 and 93%, which was roughly the same among the studies.

Conclusions

Vonoprazan-based triple therapy was effective and safe for Helicobacter pylori eradication in real-world experience, confirmed by a multicenter study and a review of the pertinent literature.

     

A prospective,multicenter survey on the validity of shorter periendoscopic cessation of antithrombotic agents in Japan

Journal of Gastroenterology - The management of antithrombotic agents for endoscopic procedures has recently focused on preventing periprocedural thrombosis in Western countries. However, this...     

Contribution of the toxic advanced glycation end-products-receptor axis in nonalcoholic steatohepatitis-related hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The main etiologies of HCC are hepatitis B virus and hepatitis C virus (HCV), and non-hepatitis B/non-hepatitis C HCC (NBNC-HCC) has also been identified as an etiological factor. Although the incidence of HCV-related HCC in Japan has decreased slightly in recent years, that of NBNC-HCC has increased. The onset mechanism of NBNC-HCC, which has various etiologies, remains unclear; however, nonalcoholic steatohepatitis (NASH), a severe form of nonalcoholic fatty liver disease, is known to be an important risk factor for NBNC-HCC. Among the different advanced glycation end-products (AGEs) formed by the Maillard reaction, glyceraldehyde-derived AGEs, the predominant components of toxic AGEs (TAGE), have been associated with NASH and NBNC-HCC, including NASH-related HCC. Furthermore, the expression of the receptor for AGEs (RAGE) has been correlated with the malignant progression of HCC. Therefore, TAGE induce oxidative stress by binding with RAGE may, in turn, lead to adverse effects, such as fibrosis and malignant transformation, in hepatic stellate cells and tumor cells during NASH or NASH-related HCC progression. The aim of this review was to examine the contribution of the TAGE-RAGE axis in NASH-related HCC.     

Functional glycine receptor in cultured human keratinocytes

We previously demonstrated that a series of neural receptors, those play a crucial role in nerve system, also expressed in epidermal keratinocytes. We also demonstrated that topical application of glycine on hairless mice skin after the barrier disruption also accelerated the barrier recovery and it was blocked by the strychnine. Glycine is known as one of the most important inhibitory neurotransmitters in the mammalian central nervous system. Thus, we hypothesized that glycine receptor also functionally expressed in the epidermal keratinocytes. In the present study, we first studied the expression of glycine receptor message in cultured human keratinocytes. Then we demonstrate for the first time the existence of a functional receptor with electrophysiological properties of glycine receptors in cultured human epidermal keratinocytes. Finally, we demonstrated immune‐histochemical study against anti‐glycine receptor subunits in human skin. Results of the present study might indicate new target of the clinical dermatology.     

Esophageal intramural pseudodiverticulosis of the residual esophagus after esophagectomy for esophageal cancer

A 91-year-old man was referred to our hospital with intermittent dysphagia. He had undergone esophagectomy for esophageal cancer(T3N2M0 Stage Ⅲ) 11 years earlier. Endoscopic examination revealed an anastomotic stricture; signs of inflammation,including redness,erosion,edema,bleeding,friability,and exudate with white plaques; and multiple depressions in the residual esophagus. Radiographical examination revealed numerous fine,gastrografinfilled projections and an anastomotic stricture. Biopsy specimens from the area of the anastomotic stricture revealed inflammatory changes without signs of malignancy. Candida glabrata was detected with a culture test of the biopsy specimens. The stricture was diagnosed as a benign stricture that was caused by esophageal intramural pseudodiverticulosis. Accordingly,endoscopic balloon dilatation was performed and antifungal therapy was started in the hospital. Seven weeks later,endoscopic examination revealed improvement in the mucosal inflammation; only the pseudodiverticulosis remained. Consequently,the patient was discharged. At the latest follow-up,the patient was symptomfree and the pseudodiverticulosis remained in the residual esophagus without any signs of stricture or inflammation.     

Characteristics of Classical Swine Fever Virus Variants Derived from Live Attenuated GPE− Vaccine Seed

The GPE⁻ strain is a live attenuated vaccine for classical swine fever (CSF) developed in Japan. In the context of increasing attention for the differentiating infected from vaccinated animals (DIVA) concept, the achievement of CSF eradication with the GPE⁻ proposes it as a preferable backbone for a recombinant CSF marker vaccine. While its infectious cDNA clone, vGPE⁻, is well characterized, 10 amino acid substitutions were recognized in the genome, compared to the original GPE⁻ vaccine seed. To clarify the GPE⁻ seed availability, this study aimed to generate and characterize a clone possessing the identical amino acid sequence to the GPE⁻ seed. The attempt resulted in the loss of the infectious GPE⁻ seed clone production due to the impaired replication by an amino acid substitution in the viral polymerase NS5B. Accordingly, replication-competent GPE⁻ seed variant clones were produced. Although they were mostly restricted to propagate in the tonsils of pigs, similarly to vGPE⁻, their type I interferon-inducing capacity was significantly lower than that of vGPE⁻. Taken together, vGPE⁻ mainly retains ideal properties for the CSF vaccine, compared with the seed variants, and is probably useful in the development of a CSF marker vaccine.     

Durable complete response to immunotherapy with anti‐PD‐1 antibody nivolumab in a patient with oral squamous cell carcinoma presenting with lung metastasis: A case report

Although the optimal treatment method for metastatic oral cancer remains largely unknown, the present case suggests that immunotherapy is a potentially promising alternative for metastatic oral cancer in which other therapies are no longer effective.     

Characterization of two cytochrome P450 monooxygenase genes of the pyripyropene biosynthetic gene cluster from Penicillium coprobium

Pyripyropenes are potent inhibitors of acyl-CoA:cholesterol acyltransferase, which were initially discovered to be produced by Aspergillus fumigatus. Recently, Penicillium coprobium PF1169 has also found to produce pyripyropene A (PyA), which exhibits insecticidal properties. Pyripyropenes are natural hybrid products of both terpenoid and polyketide origin. In our research, based on data generated using the Genome Sequencer FLX for P. coprobium PF1169, we predicted the biosynthetic gene cluster of PyA by blast analysis comparing with polyketide synthase and prenyltransferase of other species. By screening the genomic fosmid library, nine open reading frames (ppb1 to ppb9) related to the biosynthesis of PyA were deduced. Among them, two cytochrome P450 monooxygenase genes (ppb3 and ppb4) were separately introduced into the model fungus A. oryzae. Bioconversion of certain predicted intermediates in the transformants has elucidated the manner of hydroxylation in the biosynthetic pathway by the expressed products of these two genes (P450-1 and P450-2). That is, P450-1 exhibits monooxygenase activity and plays the hydroxylation role at C-11 of pyripyropene E. While P450-2 plays an active role in the hydroxylation of C-7 and C-13 of pyripyropene O.     

A toxicological evaluation of a claudin modulator, the C-terminal fragment of Clostridium perfringens enterotoxin, in mice

Tight junctions (TJs) maintain cellular polarity between the apical and basolateral region of epithelial cells. Claudin, a tetra-transmembrane protein, plays a pivotal role in the barrier function of TJs. We previously found that a claudin modulator, the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE), may be a promising candidate for improving the mucosal absorption of drugs. C-CPE is a fragment of enterotoxin, and putative CPE claudin receptors are highly expressed in liver and kidney. The safety and antigenicity of C-CPE must be evaluated for future clinical application. Therefore, we evaluated whether C-CPE administration in mice leads to tissue injury or production of antibodies. Intravenous administration of C-CPE at 5 mg/kg, which is a more than 25-fold higher dose than that used in a murine mucosal absorption model, did not increase biochemical markers of liver and kidney injury even after 11 injections once a week. Nasal C-CPE administration (2 mg/kg) once a week for 11 administrations also did not increase these biochemical markers, but 6 administrations of C-CPE resulted in elevation of C-CPE-specific serum IgG. These results indicate that development of a less antigenic claudin modulator will be essential for future clinical application of a C-CPE-based mucosal absorption enhancer.