BACKGROUND:Persistent infection with Helicobacter pylori (H. pylori) causes chronic gastric inflammation, gastric mucosal atrophy (GMA), intestinal metaplasia, and finally progression to gastric cancer. Genetic factors associated with GMA have been identified using a genome wide approach or candidate gene approach based on known functions. In this study, data-driven selection of candidate genes was conducted using publicly available databases, not based on known functions. METHOD:We hypothesized that the expression levels of some genes in the stomach may vary depending on single nucleotide polymorphisms (SNPs) and may differentially respond to H. pylori infection. Thus, the Gene Expression Omnibus database, which showed differentially expressed genes in response to H. pylori infection, and cis-expression Quantitative Trait Locus data of the stomach from the GTEx Portal were retrieved, and shared genes between the two lists were selected as candidate genes for further study. This study included 195 individuals diagnosed as H. pylori-positive. RESULT AND CONCLUSION:Four SNPs in four genes (ADORA2B, ZFAND2A, APOBEC3B, and PRMT6) were selected and examined for association with susceptibility to GMA. Among the SNPs, rs9435441 in PRMT6 was closely associated with GMA in the minor allele dominant model (p = 0.0004, OR = 2.858). This association could be difficult to identify using an approach based on the known function of PRMT6 because there have been no reports showing direct effects or function of the gene on GMA and/or related conditions. Validation using other populations and experiments to reveal the function of the gene is needed in future studies.

Cytotoxin-associated gene A (CagA) is an oncoprotein that H. pylori injects into the host’s gastric epithelial cells and that induces proinflammatory cytokines, such as interleukin (IL)-18 and IL-1β. As a result, it leads to atrophic gastritis (AG), a precancerous lesion of gastric cancer. On the other hand, host cells degrade CagA using autophagy systems. However, few studies exist about the single nucleotide polymorphisms (SNPs) in MAP1LC3A, MAP1LC3B, ATG4A, ATG4B, ATG4C, ATG7, and ATG13, which belong to the autophagy-related genes concerning AG. This study aimed to detect biomarkers associated with AG. Herein, H. pylori-positive subjects (n = 200) were divided into the AG (n = 94) and non-AG (n = 106) groups. Thirty tag SNPs were selected from the above seven candidate genes. The SNP frequency between the two groups was analyzed. The frequency of the C/T or T/T genotype at rs4683787 of ATG7 was significantly lower in the AG group than in the non-AG group (p = 0.034, odds ratio = 0.535). Based on multivariate analysis, the C/C genotype of rs4684787 and age were independently associated with gastric mucosal atrophy. This finding helps stratify the patients needing timely endoscopic screening or early eradication of H. pylori.

Background: Chronic gastritis caused by Helicobacter pylori (H. pylori) infection can progress to gastric cancer through atrophic gastritis (AG). The risk of gastric cancer increases with the progression of AG. Therefore, investigating the risk factors for the progression of AG is important. Methods: Using the GTEx and GEO databases, we extracted thirty-four candidate genes involved in the progression of AG. Then, with in silico analysis using HaploReg v4.1 and JASPAR (Matrix ID: MA0113.3), we extracted rs1231760 of RGS2 as a key single-nucleotide polymorphism (SNP) that could be involved in the functional change in the candidate gene. A correlation analysis between the selected SNP and AG in 200 H. pylori-positive and 302 H. pylori-negative participants was conducted. For functional analysis of the SNP, a dual-luciferase assay using reporter plasmids with a major or minor allele sequence was carried out. Results: The frequency of the C/C genotype of rs1231760 was higher in the AG group than in the non-AG group (p = 0.0471). Functional analysis showed that the transcriptional activities were higher at the dexamethasone-stimulating C allele than at the others (p < 0.05). Conclusions: The C/C genotype of rs1231760 in RGS2 could be a biomarker of high-risk H. pylori-positive AG because of an increase in RGS2 expression.

Helicobacter pylori (H. pylori) infection causes a progression to atrophic gastritis and results in gastric cancer. Cytotoxin-associated gene A (CagA), a major virulence factor of H. pylori, is injected into gastric epithelial cells using the type IV secretion system. On the other hand, gastric epithelial cells degrade CagA using an autophagy system, which is strictly regulated by the autophagy-related (ATG) genes. This study aimed to identify SNPs in ATG5, ATG10, ATG12, and ATG16L1 associated with gastric mucosal atrophy (GMA). Here, two-hundred H. pylori-positive participants without gastric cancer were included. The degree of GMA was evaluated via the pepsinogen method. Twenty-five SNPs located in the four candidate genes were selected as tag SNPs. The frequency of each SNP between the GMA and the non-GMA group was evaluated. The rs6431655, rs6431659, and rs4663136 in ATG16L1 and rs26537 in ATG12 were independently associated with GMA. Of these four SNPs, the G/G genotype of rs6431659 in ATG16L1 has the highest odd ratio (Odds ratio = 3.835, 95% confidence intervals = 1.337-1.005, p = 0.008). Further functional analyses and prospective analyses with a larger sample size are required.

Helicobacter pylori secretes cytotoxin-associated gene A (CagA) into the gastric epithelium, causing gastric mucosal atrophy (GMA) and gastric cancer. In contrast, host cells degrade CagA via autophagy. However, the association between polymorphisms in autophagy-related genes and GMA must be fully elucidated. We evaluated the association between single nucleotide polymorphisms (SNPs) in autophagy-related genes (low-density lipoprotein receptor-related protein 1, LRP1; capping actin protein of muscle Z-line alpha subunit 1, CAPAZ1; and lysosomal-associated membrane protein 1, LAMP1) and GMA in 200 H. pylori-positive individuals. The frequency of the T/T genotype at rs1800137 in LRP1 was significantly lower in the GMA group than in the non-GMA group (p = 0.018, odds ratio [OR] = 0.188). The frequencies of the G/A or A/A genotype at rs4423118 and T/A or A/A genotype at rs58618380 of CAPAZ1 in the GMA group were significantly higher than those in the non-GMA group (p = 0.029 and p = 0.027, respectively). Multivariate analysis revealed that C/C or C/T genotype at rs1800137, T/A or A/A genotype at rs58618380, and age were independent risk factors for GMA (p = 0.038, p = 0.023, and p = 0.006, respectively). Furthermore, individuals with the rs1800137 C/C or C/T genotype of LRP1 had a 5.3-fold higher susceptibility to GMA. These genetic tests may provide future directions for precision medicine for individuals more likely to develop GMA. LRP1 and CAPZA1 polymorphisms may be associated with the development of GMA.

Helicobacter pylori infection results in gastric cancer (GC) with gastric mucosal atrophy (GMA). Some single-nucleotide polymorphisms (SNPs) in the prostate stem cell antigen gene (PSCA) are associated with GC and duodenal ulcers. However, the relationship of other identified SNPs in PSCA with these diseases remains unclear. Herein, the association between PSCA SNPs and GMA among 195 Japanese individuals with H. pylori infection was evaluated. The definition of GMA or non-GMA was based on serum pepsinogen levels or endoscopic findings. Five tag PSCA SNPs were analyzed using PCR high-resolution melting curve analysis with nonlabelled probes. The frequencies of alleles and the genotypes of each tag SNP were compared between the GMA and non-GMA groups. Subsequently, a genetic test was performed using associated SNPs as biomarkers to detect patients developing GMA. Two tag PSCA SNPs (rs2920280 and rs2294008) were related to GMA susceptibility. Individuals with the rs2920280 G/G genotype or the rs2294008 T/T genotype in PSCA had 3.5- and 2.1-fold susceptibility to GMA, respectively. In conclusion, SNP rs2920280 is a possible biomarker for detecting individuals developing GMA. PSCA polymorphisms may be useful biomarkers for predicting GMA linked to GC risk and a screening endoscopy strategy to detect GC related to early stage H. pylori associated GMA.

Duodenogastric reflux (DGR) causes bile reflux gastritis (BRG) and may develop into gastric cancer. DGR is classified as primary in non-operated stomachs or secondary to surgical intervention. Primary DGR and Helicobacter pylori (H. pylori) infection are reportedly related. However, the mechanism is not fully understood. This study aimed to elucidate the relationship between H. pylori infection and pyloric incompetence in a non-operated stomach. A total of 502 non-operated participants who underwent an upper intestinal endoscopy were prospectively enrolled. Endoscopic findings (EAC, endoscopic atrophy classification; nodular gastritis; xanthoma; fundic gland polyp; and incompetence of pylorus), sex, age, gastrin, pepsinogen (PG) I and PG II levels were evaluated. PG I/PG II ratio, anti-H. pylori-Ab positivity, and atrophic gastritis status were significantly different between the normal and incompetent pylori (p = 0.043, <0.001, and 0.001, respectively). Open-type atrophic gastritis was significantly higher in the incompetent pylori. Incompetence of the pylorus and EAC were moderately correlated (Cramer’s V = 0.25). Multivariate analysis revealed that the presence of anti-H. pylori-Ab was the only independent factor associated with the incompetence of the pylorus, with an adjusted odds ratio of 2.70 (95% CI: 1.47–4.94, p = 0.001). In conclusion, pyloric incompetence was associated with H. pylori infection and moderately correlated to the severity of atrophic gastritis in non-operated stomachs.

Background: Helicobacter pylori is one of the most prevalent global pathogens and treatment failure is increasing due to rising antibiotic resistance.Polaprezinc is a gastric mucosal protective agent complex of zinc and L-carnosine, shown to improve efficacy when combined with triple therapy in Japan.Aim: To compare the clinical efficacy and safety of the polaprezinc combined to triple therapy versus standard triple therapy in the eradication of H. pylori.Methods: This is a randomized, parallel-group controlled, prospective multicenter study in 11 cities of China.Treatment-naïve patients with H. pylori-associated gastritis were randomly assigned to the following groups: Arm A which consists of triple-therapy (omeprazole 20mg, amoxicillin 1g, and clarithromycin 500mg twice daily) plus polaprezinc 75mg twice daily, Arm B which consists of the same triple-therapy plus polaprezinc 150mg twice daily, or Arm C which is the standard triple-therapy for 14 days.Eradication was considered successful if C 13 or C 14 urea breath test was negative 4 weeks after completion of therapy as the primary outcome.Digestive symptoms improvement 7, 14, 28 days after completion of intervention and rates of adverse effects were the secondary outcomes.Results: 332 enrolled, and 303 patients completed the study, with 106, 96, and 101 patients in Arm A, Arm B, and Arm C. In the intention-to-treat (ITT) analysis, the rate of H. pylori eradication was significantly higher for Arm A (77.0%) and Arm B (75.9%) vs Arm C (58.6%) (p<0.01),whereas there was no difference between Arm A and Arm B (P=0.90) (Table 1, Figure 1).In the per-protocol (PP) analysis, the rate of H. pylori eradication was significantly higher for Arm A (81.1%) and Arm B (83.3%) vs Arm C (61.4%) (P<0.01), while there was no difference between Arm A and Arm B (P=0.62) (Table 1, Figure 1).In all three groups, there were significant symptomatic improvement including abdominal pain, acid reflux, belching, heartburn, bloating, nausea, and vomiting at 7 days, 14 days and 28 days after treatment compared to baseline (P<0.0001).The adverse event rate of Arm B was higher than Arm A (P=0.04) and Arm C (P=0.02), including mild leukopenia, elevated liver enzymes, elevated serum uric acid, and high blood pressure, but there were no serious adverse events.Conclusions: Standard dose polaprezinc combined with standard triple therapy can significantly improve H. pylori eradication rate without an increase in adverse event and is well-tolerated.H. pylori eradication rate in the ITT and PP populations

Stable suppression of gastric acid secretion is a crucial factor in Helicobacter pylori eradication. Vonoprazan is a potassium-competitive acid blocker recently approved for use in Japan. As vonoprazan has a long duration of action and causes rapid and strong inhibition of gastric acid secretion, it has gained clinical attention for treating erosive oesophagitis, peptic ulcers, and H. pylori infection. In this review, we discuss the recent knowledge regarding the safety and efficacy of vonoprazan, focusing on its use in H. pylori eradication. The latest literature and our clinical experience have shown that vonoprazan-based therapies have satisfactory eradication rates. Additionally, vonoprazan-based therapies are associated with similar rates of adverse events as standard triple therapies with conventional proton-pump inhibitors.

Stable suppression of gastric acid secretion is a crucial factor in eradication. Vonoprazan is a potassium-competitive acid blocker recently approved for use in Japan. As vonoprazan has a long duration of action and causes rapid and strong inhibition of gastric acid secretion, it has gained clinical attention for treating erosive oesophagitis, peptic ulcers, and infection. In this review, we discuss the recent knowledge regarding the safety and efficacy of vonoprazan, focusing on its use in eradication. The latest literature and our clinical experience have shown that vonoprazan-based therapies have satisfactory eradication rates. Additionally, vonoprazan-based therapies are associated with similar rates of adverse events as standard triple therapies with conventional proton-pump inhibitors.

腸管子宮内膜症は，腸管で子宮内膜組織が異所性に増殖するまれな疾患である．症例は38歳の女性で，3か月前から腸閉塞症状を繰り返すため精査目的で当院へ紹介された．腹部造影CTで回盲部の腫瘤影と多発子宮筋腫を認めた．月経に随伴する腹部症状と，CA125の上昇より腸管子宮内膜症を疑い回盲部切除術を施行した．組織学的診断では回盲部に粘膜下層から漿膜下層にかけて子宮内膜組織の増生を認め，一部リンパ管侵襲を伴っていた．腸管子宮内膜症のリンパ行性進展を示唆する貴重な症例であり，文献的考察を加え報告する．

In era of systemic chemotherapy for colorectal liver metastasis (CLM), role of hepatic intraarterial infusion chemotherapy (HAIC) remains important. We examined treatment effects of HAIC in 36 patients with non-resectable CLM using 5-FU or CPT-11. Tumor response was complete response (CR) in 4, partial response (PR) in 19, stable disease (SD) in 6, and progressive disease (PD) in 7. Tumor control rate was 81% and response rate was 64%. Six patients showed catheter-related complications. Median survival period was 62 months in CR, and 25 with PR. HAIC has a major impact in high chemotherapy response and prolonging survival.

BACKGROUND/AIMSDespite recent advances in surgical techniques, blood loss is an important factor associated with postoperative outcomes in pancreatectomy. It is useful to identify risk factors of increased blood loss.METHODOLOGYThe clinical records of 161 patients who underwent an elective pancreatectomy for peripancreatic diseases between 1994 and March 2011 were retrospectively examined. Univariate and multivariate analysis of clinicopathological and surgical parameters influencing intraoperative blood loss were performed. We determined the cut-off value of the amount of blood loss based on the analyzed results.RESULTSThe mean and median blood loss was 1346±901 and 1070 mL, respectively. Red cell blood transfusion was performed in 72 patients (45%). Based on ROC analysis, the predictive value of blood loss in patients who received red cell blood transfusion was 880 mL (p <0.001); however, blood loss was not significantly associated with postoperative complications (p = 0.40). The cut-off level of estimated amount of blood loss in the present study was set at 880 mL. Male patients, fatty pancreas, higher serum alkaline phosphatase level, longer operating time, performance of pancreaticoduodenectomy (PD) and combined resections of adjacent major vessels were associated with significantly more increased blood loss (p <0.05). Based on multivariate analysis, longer operation time over 480 minutes and performance of PD were significantly associated with increased blood loss (p <0.05).CONCLUSIONSAttempting to reduce operating time in cases of PD is necessary to reduce intraoperative blood loss.

BACKGROUND/AIMS:The present study aimed to elucidate the relationship between microvessel count (MVC) according to CD34 expression and clinicopathological characteristics or prognosis in pancreatic carcinoma (PC) patients who underwent hepatectomy.METHODOLOGY:CD34 expression was analyzed using immunohistochemical methods. Mean MVC in 5 areas per specimen and clinicopathological factors were consecutively examined in 42 PC patients.RESULTS:Median MVC for PC patients was 123/mm2, which was applied as a cut-off value. Higher MVC was significantly associated with the advanced Japanese tumor-node-metastasis stage IVa and IVb (p=0.034). Univariate survival analysis identified higher carcinoembryonic antigen (CEA) and CA19-9 level, infiltrative type on macroscopic examination, invasive ductal carcinoma, node metastasis and higher tumor-node-metastasis classification were significantly associated with poor survival. The 5-year overall survival rate in the higher MVC group tended to be lower than that in the higher MVC group (37 vs. 55%), but not statistically significant (p=0.15).CONCLUSIONS:Tumor MVC might be a candidate prognostic marker of PC patient survival after pancreatectomy and further investigation in a larger series is warranted to clarify the significance of this marker.