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The advantage of endoscopic submucosal dissection (ESD) is that it is less invasive than surgery. ESD is one of the best treatments for older patients as surgery in this age group of patients is difficult. However, it is unclear how much lower the physical stress of ESD is compared with that of surgery. Thus, objective methods are required to assess physical stress in patients who have undergone ESD. The current review of ESD aimed to summarize the recent advancements in the assessment of physical stress during the perioperative period, focusing on changes in energy metabolism and serum opsonic activity (SOA). Based on metabolic changes, resting energy expenditure (REE) was measured using an indirect calorimeter. The stress factor calculated from the REE and the basal energy expenditure computed using the Harris-Benedict equation can be used to assess physical stress. SOA was assessed using the chemiluminescence method, wherein the use of chemiluminescent probes (

A number of studies have revealed the association between Helicobacter pylori (H. pylori) infection and the gut microbiota. More than half of the investigations on the impact of H. pylori on the gut microbiota have been the sub-analyses of the influence of eradication therapy. It was observed that H. pylori eradication altered gut microbiota within a short period after eradication, and majority of the alterations took a long period of time to reverse back to the original. Changes in the gut microbiota within a short period after eradication may be attributed to antibiotics and proton pump inhibitors. Modification of gastric acidity in the stomach caused by a long-term H. pylori infection alters the gut microbiota. Analysis of the gut microbiota should be conducted in a large population, adjusting for considerable biases associated with the composition of the gut microbiota, such as age, sex, body mass index, diet and the virulence of H. pylori.

Esophageal endoscopic submucosal dissection (ESD) is considered to be more complex than gastric ESD. This study aimed to assess the physical invasiveness of esophageal ESD during perioperative periods by measuring resting energy expenditure (REE). The factors affecting REE that could be used to identify patients requiring perioperative management were also investigated. Overall, 75 patients who had undergone esophageal ESD were prospectively enrolled. REE, body weight, and basal energy expenditure were measured on the day of and the day following ESD. The mean REE/body weight was 20.2 kcal/kg/day on the day of ESD and significantly increased to 23.0 kcal/kg/day one day after ESD. The stress factor on the day after ESD was 1.11. White blood cell, neutrophil, and C-reactive protein levels increased on the day after ESD and correlated with the changes in REE. Among the factors including age, body mass index, total resection area, operation time, and sarcopenia, only the total resection area was associated with changes in REE. In conclusion, energy metabolism increases during the perioperative period for esophageal ESD. The increase in the stress factor for esophageal ESD was higher than that in gastric and colorectal ESD. Furthermore, patients with large resection areas require greater attention in perioperative management.

Background: Because no therapeutic regimens have an eradication rate of 100%, post-treatment evaluation is necessary to ensure that adequate eradication therapy for Helicobacter pylori has been provided. The fact that not all patients are evaluated after eradication therapy is a serious concern for both the medical care system and medical economy. Method: We performed a retrospective study of 411 patients who received first-line H. pylori eradication therapy at Fuyoukai Murakami Hospital from October 1, 2014 to March 31, 2016. We calculated the rate of post-treatment follow-up at 1 year after completing the eradication therapy. In addition, we excluded 76 patients who definitely received post-treatment evaluation because of follow-up appointments with gastroenterologists (n = 29) or return visits to other physicians (n = 47) and included 335 patients in the final study population. We used logistic regression models for identifying the relevant factors contributing to the completion of post-eradication follow-up. Results: The rate of completion of post-eradication follow-up was 78.8% (324/411). Multivariate analysis revealed that the adjusted odds ratios for age (≥ 48 years), gender (female) and preventive measures for gastric cancer (esophagogastroduodenoscopy after radiographic screening for gastric cancer and a desire to be examined for H. pylori infection) were 1.85 [95% confidence interval (CI): 1.11–3.09; p < 0.05], 1.89 [95% CI: 1.07–3.34; p < 0.05] and 4.01 [95% CI: 1.61–10.0; p < 0.01], respectively. Conclusion: Age ≥ 48 years, female gender and preventive measures for gastric cancer were independently related to a higher rate of completion of post-eradication follow-up.

A 76-year-old man was referred to our hospital for examination and treatment of dysphagia. He has been taking enteric-coated aspirin for myocardial infarction. Esophagogastroduodenoscopy (EGD) revealed the presence of esophageal ulcers in the distal esophagus and five to six tablets of enteric-coated aspirin. The esophageal ulcers were believed to have been caused by the retention of aspirin within the esophagus due to achalasia. We substituted enteric-coated aspirin with powdered aspirin. A follow-up EGD performed 1 month later showed improvement of esophageal mucosa. The patient was diagnosed with type I achalasia. Per-oral endoscopic myotomy was performed, and his symptoms improved after the procedure. Although a few studies have investigated the direct effect of aspirin, none of them has reported on the direct effect of aspirin on the esophagus. It might be effective to administer powdered aspirin for patients with achalasia to prevent esophageal ulcers caused by the direct effect of aspirin.

Background: Although infection with Helicobacter pylori and subsequent atrophic gastritis modulate the gastric conditions, their relationship with the gut microbiota in ­Japanese population has not been clearly characterized. Methods: A cohort of 1,123 subjects who participated in a health survey was studied. Infection of H. pylori was defined by both serum antibody and stool antigen test. The presence and severity of atrophic gastritis were defined by serum levels of pepsinogens. The relative abundance of each bacterial species in fecal samples was calculated by using 16S ribosomal RNA amplification, and the composition ratios of bacterial taxa were evaluated using propensity score matching. Results: The abundance of 3 orders, 4 families, and 4 genera was significantly higher in H. pylori-infected subjects than in noninfected subjects (false discovery rate [FDR] H. pylori-infected subjects with severe atrophic gastritis, the abundance of the class Bacilli, order Lactobacillales, family Streptococcaceae, and genus Streptococcus was significantly higher than that in H. pylori-infected subjects without atrophic gastritis (FDR < 0.05). Conclusions: A significant increase in the relative abundance of several taxa was observed in gut microbiota of Japanese subjects with H. pylori infection. Among the subjects with severe atrophic gastritis, the increase in the genus Streptococcus is a remarkable characteristic.

This study aimed to elucidate whether changes in serum opsonic activity measured by lucigenin-dependent chemiluminescence and luminol-dependent chemiluminescence are useful for estimating physical stress during the perioperative period of gastric endoscopic submucosal dissection. Serum opsonic activity in the peripheral blood of 87 patients was examined in the morning of the day of endoscopic submucosal dissection, the next day, and at 4 days after endoscopic submucosal dissection. Peak height and area under the curve for lucigenin-dependent chemiluminescence were 106.1 ± 22.7% and 102.0 ± 24.7% on the day of endoscopic submucosal dissection, which increased significantly to 113.6 ± 29.4% and 111.0 ± 29.1% on the next day (both p

A number of studies have revealed the association between Helicobacter pylori (H. pylori) infection and the gut microbiota. More than half of the investigations on the impact of H. pylori on the gut microbiota have been the sub-analyses of the influence of eradication therapy. It was observed that H. pylori eradication altered gut microbiota within a short period after eradication, and majority of the alterations took a long period of time to reverse back to the original. Changes in the gut microbiota within a short period after eradication may be attributed to antibiotics and proton pump inhibitors. Modification of gastric acidity in the stomach caused by a long-term H. pylori infection alters the gut microbiota. Analysis of the gut microbiota should be conducted in a large population, adjusting for considerable biases associated with the composition of the gut microbiota, such as age, sex, body mass index, diet and the virulence of H. pylori.

Background The clinical significance of non-Helicobacter pylori Helicobacter (NHPH) is still unknown. There are many reports of NHPH-infected patients suffering from gastric diseases. Here, we investigated the polymerase chain reaction (PCR) positivity of NHPH infection in gastric disease patients who were negative for H. pylori (Hp) by the rapid urease test and by pathological observation. Materials and methods We collected the 296 endoscopically obtained gastric mucosal samples of Hp-negative gastric disease patients diagnosed based on a rapid urease test and pathology from 17 hospitals in Japan from September 2013 to June 2019, and we analyzed the existence of Hp and NHPH by PCR. The samples were also treated by indirect immunohistochemistry using an anti-Helicobacter suis VacA paralog antibody and were observed by confocal laser microscopy. Results Among the 236 non-Hp-eradicated cases, 49 cases (20.8%) were positive for NHPH. Among them, 20 cases were positive for Helicobacter suis, 7 cases were positive for Helicobacter heilmannii sensu stricto/ Helicobacter ailurogastricus (Hhss/Ha), and the other 22 cases could not be identified. The regional differences in the infection rates were significant. Forty percent of the nodular gastritis cases, 24% of the MALT lymphoma, 17% of the chronic gastritis cases, and 33% of the gastroduodenal ulcer cases were NHPH positive. Forty-five patients had been treated with one of the four types of combinations of a proton pump inhibitor and two antibiotics, and in all of these cases, the NHPH diagnosed by PCR was successfully eradicated. Immunohistochemistry using the Helicobacter suis-specific HsvA antibody coincided well with the PCR results. Among the 29 post-Hp eradication cases, three were NHPH positive, including one Hhss/Ha-positive case. Thus, approx. 20% of the Hp-negative non-Hp-eradicated gastric disease patients treated at 17 hospitals in Japan were infected with NHPH.

The clinical significance of non-Helicobacter pylori Helicobacter (NHPH) is still unknown. There are many reports of NHPH-infected patients suffering from gastric diseases. Here, we investigated the polymerase chain reaction (PCR) positivity of NHPH infection in gastric disease patients who were negative for H. pylori (Hp) by the rapid urease test and by pathological observation.We collected the 296 endoscopically obtained gastric mucosal samples of Hp-negative gastric disease patients diagnosed based on a rapid urease test and pathology from 17 hospitals in Japan from September 2013 to June 2019, and we analyzed the existence of Hp and NHPH by PCR. The samples were also treated by indirect immunohistochemistry using an anti-Helicobacter suis VacA paralog antibody and were observed by confocal laser microscopy.Among the 236 non-Hp-eradicated cases, 49 cases (20.8%) were positive for NHPH. Among them, 20 cases were positive for Helicobacter suis, 7 cases were positive for Helicobacter heilmannii sensu stricto/ Helicobacter ailurogastricus (Hhss/Ha), and the other 22 cases could not be identified. The regional differences in the infection rates were significant. Forty percent of the nodular gastritis cases, 24% of the MALT lymphoma, 17% of the chronic gastritis cases, and 33% of the gastroduodenal ulcer cases were NHPH positive. Forty-five patients had been treated with one of the four types of combinations of a proton pump inhibitor and two antibiotics, and in all of these cases, the NHPH diagnosed by PCR was successfully eradicated. Immunohistochemistry using the Helicobacter suis-specific HsvA antibody coincided well with the PCR results. Among the 29 post-Hp eradication cases, three were NHPH positive, including one Hhss/Ha-positive case. Thus, approx. 20% of the Hp-negative non-Hp-eradicated gastric disease patients treated at 17 hospitals in Japan were infected with NHPH.

ABC classification has been used to assess the risk for gastric cancer. The current problem of ABC classification is that Group A contains individuals with current and past H. pylori infection. The aims of this study were to assesse the proportion of current and past infection in Group A and to establish a criteria for the identification of subjects with past infection from Group A subjects with negative results of urea breath test (UBT) and/or stool antigen test. 201 subjects classified into Group A received UBT and/or stool antigen test, and also subsequent upper gastrointestinal endoscopy. The subjects were classified by the status of H. pylori infection defined by endoscopic findings. Levels of pepsinogen (PG) I, PG II and PG I/II ratio were compared between the groups, and receiver operating characteristic curves were constructed to extract the corresponding cutoff values. 22 subjects were tested positive by UBT and/or stool antigen test. Endoscopic images of 157 out of 179 subjects were studied. 15 of the subjects were regarded to have past H. pylori infection. The optimal cut-off value of PG I and PG I/II ratio for the determination of past H. pylori infection were ≤ 31.2 ng/mL and ≤ 4.6, respectively. Approximately 20% of Group A subjects have current or past H. pylori infection. Addition of UBT and/or stool antigen test can identify current but not past infection. Serum PG levels would be useful to identify subjects with past H. pylori infection.

The aim of this study was to assess the perioperative invasiveness of endoscopic submucosal dissection for colorectal cancer quantitatively by using energy metabolism. In fifty-three patients who underwent endoscopic submucosal dissection for colorectal cancer, resting energy expenditure using an indirect calorimeter, body weight and basal energy expenditure using the Harris-Benedict equation before and after endoscopic submucosal dissection. Resting energy expenditure/body weight and resting energy expenditure/basal energy expenditure were 19.7 ± 2.5 kcal/kg/day and 0.96 ± 0.12 on the day of endoscopic submucosal dissection, whereas one day after the endoscopic submucosal dissection they increased to 21.0 ± 2.9 kcal/kg/day and 1.00 ± 0.13 (p

A reddish depressed lesion was found in the corpus of the stomach of a 56-year-old man. Gastric biopsy showed no findings of mucosa-associated lymphoid tissue lymphoma, including lympho-epithelial lesions. A urea breath test, stool antigen test and serum IgG antibody to Helicobacter pylori test were negative. Magnifying endoscopy using narrow-band-imaging showed no malignant structures. Gastric biopsy specimens were subjected to immunohistochemistry and a polymerase chain reaction, which identified Helicobacter suis infection. Triple therapy with esomeprazole, metronidazole, and amoxicillin was administered for 10 days. Three months later, endoscopy showed the significant improvement of the lesion. H. suis infection should be considered in chronic gastritis patients without H. pylori infection.

Objective CYP2C19 metabolic activity influences the efficacy of Helicobacter pylori eradication therapies comprising PPIs. Rabeprazole (RPZ) and esomeprazole (EPZ) are PPIs not extensively metabolized by CYP2C19. The aim of this study was to elucidate whether or not first-line triple therapies using RPZ or EPZ are equally effective in Japanese patients with different CYP2C19 genotypes. Methods Two-hundred patients infected with H. pylori were randomized to receive one of the following regimens: amoxicillin (750 mg), clarithromycin (200 mg), and either esomeprazole (20 mg) (EAC group) or rabeprazole (10 mg) (RAC group), twice a day for one week. The CYP2C19 polymorphisms were determined by polymerase chain reaction and the serum level of pepsinogens was measured. Results The eradication rates of the EAC and RAC regimens were 79.8% (95% confidential interval: 71.7-89.0%) and 74.7% (66.0-83.4%), respectively, in a per protocol (PP) analysis (p=0.488). The eradication rates of the EAC and RAC regimens were not significantly different between patients with the homo EM genotype (p=0.999) or hetero IM or PM genotypes (p=0.286). A lower PG I/II ratio was associated with lower eradication rates (p=0.025). Conclusion Although the eradication rate was less than 80%, the EAC and RAC regimens were equally effective in each CYP2C19 genotype group. The PG I/II ratio was associated with the results of EAC and RAC therapy in this series of patients.

Background: The primary cause of osteoporosis in women is increased bone resorption and decreased bone density associated with reduced estrogen secretion. Several studies have demonstrated a relationship between Helicobacter pylori infection and osteoporosis regardless of estrogen levels. This study examined the relationship between H. pylori infection and osteopenia together with estrogen levels, calcium intake, and several lifestyle factors. Methods: This study included 473 healthy women who underwent a general health examination. Multivariate analysis was performed, with age, body mass index (BMI), smoking habit, drinking habit, exercise habit, schooling duration, estradiol levels, birth history, calcium intake, schooling duration, smoking habit, drinking habit, exercise habit, and H. pylori infection as independent variables and the presence of osteopenia as a dependent variable. Results: The adjusted OR for osteopenia with H. pylori infection was 0.95 (95% CI 0.55-1.63, p = 0.84). In contrast, osteopenia was significantly associated with age, low BMI, lesser schooling period, low estradiol levels, and low calcium intake. Conclusions:H. pylori infection was not a significant risk for osteopenia by the multivariate analysis, which included the primary confounding factors. Significant factors, such as estradiol and calcium intake, should be assessed together to study the association of H. pylori infection and osteopenia.

Vonoprazan (VPZ)-based triple therapy has been reported to have greater efficacy than a proton pump inhibitor (PPI)-based triple therapy for Helicobacter pylori (H. pylori) eradication. However, because VPZ is more expensive than PPIs such as rabeprazole (RPZ), economic evaluation is essential.We performed a retrospective study on 209 patients who underwent first-line eradication of H. pylori infection in Fuyoukai Murakami Hospital from 1 March 2015 to 31 March 2016. Patients who received VPZ, amoxicillin (AMPC) and clarithromycin (CAM) were assigned to the VPZ/AC group (n = 111) and patients who received RPZ, AMPC and CAM to the RPZ/AC group (n = 98). We compared the patients' backgrounds, including age, gender, use of high-dose CAM, past history of peptic ulcer, smoking and drug-related adverse events between the two groups. We defined cost as direct medical costs per patient and effectiveness as the first-line eradication rate in the intention-to-treat (ITT) analysis and analyzed the cost-effectiveness using the cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER).There was no significant difference in the patients' backgrounds. The ITT analysis revealed an eradication rate of 94.6% for VPZ/AC and 86.7% for RPZ/AC. VPZ/AC cost 1155.4 Japanese yen (JPY) higher than RPZ/AC (34063.4 vs. 32908.0, JPY). CER of VPZ/AC was less than that of RPZ/AC (360.1 vs. 379.4, JPY per percent) and ICER of VPZ/AC was 147.0 JPY (1.28 Euro (EUR), 1 EUR =115 JPY) per percent.VPZ/AC was more cost-effective than RPZ/AC as first-line therapy for H. pylori eradication.

A 69-year-old woman had received hemodialysis for chronic renal failure and was taking lanthanum carbonate since 63 years of age. She presented with appetite loss and nausea. We performed esophagogastroduodenoscopy, which revealed multiple longitudinal white plaques in the esophagus. Lesion biopsies showed lanthanum deposition, and lanthanum carbonate was found histologically by energy-dispersive X-ray spectroscopy. The plaques of this patient appeared like those of dabigatran-induced esophagitis, and may have occurred due to long-term contact of the esophageal epithelium with lanthanum carbonate because patient spent time in lying state. Although a few studies regarding lanthanum deposition in the stomach have been conducted, there are no reports on lanthanum deposition in the esophagus. This case suggests that the presence of longitudinal white plaques in the esophagus may indicate lanthanum deposition.

Endoscopic sub-mucosal dissection (ESD) is considered as a low-invasive treatment for early-stage colorectal cancer, but the degree of invasiveness has not been well investigated. The aim of this study was to evaluate the physical stress due to colorectal ESD based on changes in serum opsonic activity (SOA). SOA was examined by measuring reactive oxygen species (ROS) produced by neutrophils using lucigenin-dependent chemiluminescence (LgCL) and luminol-dependent chemiluminescence (LmCL). Sixty-nine patients were enrolled into the study and examined SOA in the morning of the day of ESD, the next day, and at four days after ESD. The peak height (PH) and area under the curve (AUC) of LgCL showed no significant difference between the day and the next day, whereas the PH and AUC for LgCL were significantly higher four days after ESD than on the day of ESD (

Although decreased calcium absorption, decreased bone formation, alcohol drinking, and smoking have been considered as causes of osteopenia in men, the cause is unknown in half of the cases. Many reports highlighted the association between Helicobacter pylori infection and osteoporosis, mainly in East Asia and Japan. To identify relevant factors of osteoporosis in men, we examined estrogen and calcium intakes and other lifestyle factors together with gastric mucosal atrophy caused by Helicobacter pylori infection. This study is a cross-sectional study design of 268 healthy men who underwent general medical examinations. Multivariate analysis was performed, with age, body mass index, smoking habit, drinking habit, exercise habit, estradiol level, calcium intake, and Helicobacter pylori infection and its associated gastric mucosal atrophy as the independent variables and the presence of osteopenia as the dependent variable. The adjusted odds ratio was 0.74 (95% Confidence Interval [0.29, 1.90], p = .531) and 1.31 (95% Confidence Interval [0.54, 3.21], p = .552), when Helicobacter pylori infection was positive without and with gastric mucosal atrophy, respectively. Helicobacter pylori infection and gastric mucosal atrophy were not significant factors. Low body mass index, smoking habit, and low calcium intake were significantly associated with decreased bone density. In conclusion, Helicobacter pylori infection was not a significant risk, whereas low body mass index, current smoking, and lower calcium intake had a significant influence on the development of osteopenia in men.

Background Since "Helicobacter pylori (H. pylori) infection" was set as the indication in the Japanese Society for Helicobacter Research (JSHR) Guidelines 2009, eradication treatment for H. pylori gastritis is covered under insurance since 2013 in Japan, and the number of H. pylori eradication has rapidly increased. Under such circumstances, JSHR has made the third revision to the "Guidelines for diagnosis and treatment of H. pylori infection" for the first time in 7 years. Methods The Guideline Committee held 10 meetings. Articles published between the establishment of the 2009 Guidelines and March 2016 were reviewed and classified according to the evidence level; the statements were revised on the basis of this review. After inviting public comments, the revised statements were finalized using the Delphi method. Results There was no change in the basic policy that H. pylori infectious disease is an indication for eradication. Other diseases presumed to be associated with H. pylori infection were added as indications. Serum pepsinogen level, endoscopic examination, and X-ray examination were added to the diagnostic methods. The effects of 1-week triple therapy consisting of potassium-competitive acid blocker (P-CAB), amoxicillin, and clarithromycin have improved, and high eradication rates can also be expected with proton pump inhibitors (PPI) or P-CAB combined with amoxicillin and metronidazole. If the susceptibility test is not performed, the triple PPI or P-CAB/amoxicillin/metronidazole therapy should be chosen, because the PPI/amoxicillin/metronidazole combination demonstrated a significantly higher eradication rate than PPI/amoxicillin/clarithromycin. In the proposal for gastric cancer prevention, we divided gastric cancer prevention measures by age from adolescent to elderly, who are at an increased gastric cancer risk, and presented measures for gastric cancer prevention primarily based on H. pylori eradication. Conclusion We expect the revised guidelines to facilitate appropriate interventions for patients with H. pylori infection and accomplish its eradication and prevention of gastric cancer.

Equol is a metabolite of isoflavone daidzein and has an affinity to estrogen receptors. Although equol is produced by intestinal bacteria, the association between the status of equol production and the gut microbiota has not been fully investigated. The aim of this study was to compare the intestinal bacteria responsible for equol production in gut microbiota between equol producer and non-producer subjects regarding the intake of daidzein. A total of 1044 adult subjects who participated in a health survey in Hirosaki city were examined. The concentration of equol in urine was measured by high-performance liquid chromatography. The relative abundances of 8 bacterial species responsible for equol production in the gut microbiota was assessed using 16S rRNA amplification. There were 458 subjects identified as equol producers. The proportion of equol production status and the intake of daidzein increased with age. Daily intake of daidzein was larger in equol-producer. The intestinal bacteria, which convert daidzein to equol were present in both equol producers and non-producers. However, the relative abundance and the prevalence of Asaccharobacter celatus and Slackia isoflavoniconvertens were significantly higher in equol producers than those in equol non-producers. The intestinal bacteria that convert daidzein to equol are present in not only the equol producers but also in the non-producers. The daidzein intake is associated with the equol production status through an increase of A. celatus and S. isoflavoniconvertens in the gut microbiota.

We describe herein a case of severe relapsed pyoderma gangrenosum (PG) concomitantly with severe pouchitis treated by tacrolimus. A 25-year-old woman had undergone proctocolectomy with construction of ileo-anal pouch surgery for refractory ulcerative colitis (UC). She first developed PG with refractory pouchitis, and infliximab (IFX) was administered to induce remission due to resistance to glucocorticoid therapy. After achieving remission, IFX was stopped. Five years later, severe skin ulcers concomitantly with severe pouchitis recurred and treatment with 30 mg oral prednisolone (PSL) combined with topical tacrolimus showed partial improvement. When PSL was tapered to 15 mg, the skin ulcers and diarrhea aggravated. Endoscopy revealed multiple ulcers in the ileal pouch. Treatment with oral tacrolimus was initiated for severe pouchitis and refractory PG. Forty days later, all skin ulcers became scars and multiple ulcers in the ileal pouch were also improved. Our case suggests that oral tacrolimus treatment could be a valuable treatment option for UC patients with refractory PG and pouchitis.

In Japan, both a stick-type kit and an enzyme-linked immunosorbent assay (ELISA) kit are available for the detection of antibodies to Helicobacter pylori in urine. However, the accuracy of these tests has not been fully examined in northern Japanese populations. Urine samples from 359 subjects were tested using a stick-type H. pylori-antibody detection kit (RAPIRUN), and urine samples from 201 subjects were tested using an ELISA-based test (URINELISA). The prevalence of H. pylori infection was determined by the 13C-urea breath test (UBT) and a monoclonal antibody-based stool antigen test (TPAg). Subjects were considered to have the infection if either the UBT or rapid TPAg results were positive. The percentage of positive test results for RAPIRUN and URINELISA was 54.0% and 40.8%, respectively. Sensitivity and specificity were 83.3% and 67.0%, respectively, for RAPIRUN and 86.5% and 85.8% for URINELISA. Nineteen subjects had cut-off index values of between 0.4 and 0.9 by URINELISA, and 4 of these subjects (21.1%) were found to be infected with H. pylori. The urine-based ELISA was more accurate than the rapid stick-type kit in these patients. If negative ELISA results are near the cut-off value, subjects should receive an additional test to determine whether they are infected with H. pylori.

BACKGROUND: Febrile neutropenia (FN) is often observed in patients with hematological malignancies (HEM), especially in those with acute leukemia (AL). Monotherapy with antipseudomonal beta-lactams, such as cefepime, carbapenem, or piperacillin-tazobactam, is recommended as first-line empiric antibacterial therapy in FN patients. The efficacy of meropenem (MEPM) as empiric monotherapy for FN patients with cancer has been assessed in randomized comparative trial against cefepime, imipenem/cilastain, ceftazidime with or without amikacin, and piperacillin-tazobactom. Because of those studies, MEPM is considered a standard antibiotic for the empiric treatment of FN patients with HEM.In contrast, doripenem (DRPM) is a relatively new carbapenem, and the clinical study about efficacy and safety of DRPM in FN patients with HEM is limited. Therefore, we conducted a randomized, cooperative group, open-label trial comparing DRPM (1.0 g every 8 hours) with MEPM (1.0 g every 8 hours) as the first-line empirical antibacterial therapy for high-risk FN patients with AL and myelodysplastic syndrome (MDS). METHODS: One hundred and thirty-three hospitalized patients with acute leukemia or high-risk myelodysplastic syndrome, who developed high-risk FN during or after chemotherapy (AML 77, ALL 43, APL 9, ATL 1, MDS (RAEB-2) 3cases) were randomized to each drug group (DRPM, 65; MEPM, 68). The study drug was started to administer as a mono-therapy and continued at least for 5 days without drug toxicity, and the efficacy and safety were evaluated. RESULTS: The success rate (Resolution of fever within 3 to 5 days without treatment modification: the primary endpoint) was higher in the DRPM group than in the MEPM group (60.0% vs. 45.6%), although the difference was not significant (P = 0.136). However, resolution of fever within 7 days of treatment was significantly higher in the DRPM group than in the MEPM group (78.4% vs. 60.2%, respectively, P = 0.037). Otherwise, the cumulative number of afebrile cases by day14 was 87.7% and 83.8% in the DRPM and MEPM group, respectively (P = 0.523). The success rate did not depend on neutrophil recovery: success rates for the DRPM group were 58.3% and 60.9%, with and without neutrophil recovery, respectively; success rates for the MEPM group were 33.3% and 40.9%, with and without neutrophil recovery, respectively (P = 0.233, P = 0.346). In all, 40.0% of the DRPM group and 32.3% of the MEPM group received anti-MRSA agent, as empiric or targeted antibacterial therapy of persistent or recurrent fever considering of infections by gram-positive bacteria, including methicillin-resistant species. Antifungal medications were added to 21.5% of the DRPM group and 13.2% of the MEPM group, as empiric or preemptive therapy of persistent or recurrent fevers believed to be caused by fungal infections. Survival rates at 30 days after the start of administration were 98.5% and 100% in the DRPM and MEPM group, respectively (P = 0.304). The rates of adverse events did not significantly differ between the DRPM and MEPM group (38.5% vs. 41.2%, respectively, P = 0.749), and these adverse events were clinically acceptable in the two groups, and most of patients could continue the treatment by both study drugs. CONCLUSIONS: Our clinical study suggested that DRPM had the non-inferiority of efficacy in comparison with MEPM as the first-line therapy in high-risk FN patients with AL and MDS, and both drugs could be well tolerated clinically. Disclosures Oyake: Kyowa-Hakko Kirin: Honoraria; Celgene: Honoraria; Chugai: Honoraria; Astellas: Speakers Bureau. Hanamura:Sanofi: Research Funding; Taiho: Research Funding; MSD: Research Funding; Chugai: Research Funding; Eli Lilly: Research Funding; Fujimoto: Research Funding; Zenyaku: Research Funding; Yamada Yohojo: Research Funding; Chugai: Research Funding; Astellas: Research Funding; Shionogi: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Eisai: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Kyowa-Hakko Kirin: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Ono: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; AbbVie: Honoraria; Mundi: Honoraria; Nihon Shinyaku: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding. Ito:Bristol-Myers Squibb: Honoraria; Ono: Honoraria; Celgene: Honoraria.

Despite the recent development of biological modifiers for inflammatory bowel diseases (IBD), there continues to be considerable interest in fermented medicines because of its negligible adverse effects. We previously showed that the synbiotic Gut Working Tablet (GWT) alleviates experimental colitis. Here we show that GWT is capable of ameliorating jejunoileal mucosal injury, which is frequently seen with IBD. We created experimental jejunoileal mucositis in rats by injection of methotrexate (MTX) which increases intestinal permeability, a hallmark finding of IBD. Administering GWT to MTX-injected rats restored intestinal integrity by reversing villi shortening, crypt loss, and goblet cell depletion in the mucosa. Also GWT reduced activities of myeloperoxidase and lipid peroxidase and increased superoxide dismutase activity, which is critical for maintaining intestinal function. We further found that GWT suppressed mRNA expression of tumor necrosis factor-α(TNF-α) and interleukin-12 (IL-12) in macrophage and reduced TNF-αmRNA expression in specimens with experimental colitis, which is in contrast to VSL#3 that enhanced TNF-αproduction. Together, the current and previous animal studies clearly demonstrate the protective role of GWT in chemically induced enterocolitis. Crohn’s disease, a well-known IBD, can affect any portion of the intestine, and these results suggest that GWT may be useful as a novel therapeutic or maintenance therapy for IBD.

Background and study aims Although endoscopic transpapillary gallbladder drainage (ETGBD) is reportedly useful in patients who have acute cholecystitis, its efficacy has not been compared to that of percutaneous transhepatic gallbladder drainage (PTGBD). We retrospectively compared the efficacy and safety of ETGBD and PTGBD in patients with acute cholecystitis. Patients and methods We studied 75 patients who required gallbladder drainage for acute cholecystitis between January 2014 and December 2016. Using propensity score matching analysis, we compared the clinical efficacy and length of hospitalization in patients successfully treated with ETGBD and PTGBD. Moreover, we assessed the predictive factors for hospitalization period Results ETGBD and PTGBD were successfully performed in 33 patients (77 %) and 42 patients (100 %) (P Conclusions ETGBD was shown to be as useful as PTGBD for treatment of acute cholecystitis and was associated with shorter hospitalization period. ETGBD can be an alternative treatment option for acute cholecystitis at times when PTGBD is not possible.

Objective Although several pre-endoscopic scoring systems have been used to predict the mortality or the need for intervention for upper gastrointestinal bleeding, their usefulness to predict the failure of endoscopic hemostasis in bleeding gastroduodenal peptic ulcers has not yet been fully investigated. In this study, we evaluated the usefulness of the Glasgow-Blatchford score (GBS), the clinical Rockall score (CRS), and the AIMS65 score in predicting the failure of endoscopic hemostasis in patients with bleeding gastroduodenal peptic ulcers. Methods We retrospectively evaluated 226 consecutive emergency endoscopic cases with bleeding gastroduodenal peptic ulcers between April 2010 and September 2016. The study outcome was the failure of first endoscopic hemostasis. The GBS, CRS, and AIMS65 scores were assessed for their ability to predict the failure of endoscopic hemostasis using a receiver-operating characteristic curve. Results Eight cases (3.5%) failed to achieve first endoscopic hemostasis. Surgery was required in six cases, and interventional radiology was required in two cases. The GBS was superior to both the CRS and the AIMS65 score in predicting the failure of endoscopic hemostasis [area under the curve, 0.77 (95% confidence interval, 0.64-0.90), 0.65 (0.56-0.74) and 0.75 (0.56-0.95), respectively]. No failure of endoscopic hemostasis was noted in cases in which the patient scored less than GBS 10 and CRS 2. Conclusion The GBS was the most useful scoring system for the prediction of failure of endoscopic hemostasis in patients with bleeding gastroduodenal peptic ulcers. The GBS was also useful in identifying the patients who did not require surgery or interventional radiology.

CD56, the neural cell adhesion molecule (NCAM), is a member of the immunoglobulin superfamily and is associated with cell-to-cell adhesion and migration.1 Among haematological malignancies, CD56 expression has been described mainly in NK/T cell lymphoma, plasma cell myeloma and acute myeloid leukaemia, and rarely in B cell lymphomas, accounting for no more than 0.5% of all B lymphomas.2–8 Malignant lymphoma constitutes

Background and Aim Gut Working Tablet (GWT) is a Japanese traditional fermented medicine based on Aspergillus oryzae NK-fermented grain germ. Although GWT has been used by patients with constipation, the mechanism has not been investigated. The aim of this study was to examine the possible mechanisms of the effect of GWT on constipation. Methods The effect of GWT water extracts on gut contractility using ileum strips from guinea pig and on the growth of Bifidobacterium longum were examined in vitro. The 14 Sprague Dawley rats were administered loperamide at 10 mg/day per kg for 3 days. They were fed with and without 5% of GWT before and during administration of loperamide. Number of stools and weight of feces were measured before and during administration of loperamide. The concentrations of short-chain fatty acids (SCFAs) in the feces and cecal contents were measured by gas chromatography. Results GWT water extracts dose-dependently induced ileal contractile responses, which were inhibited by atropine. The growth of B. longum was increased in the presence of GWT water extracts in a dose-dependent manner (P

Background and Aim In Japan, the prevalence of Helicobacter pylori infection is decreasing and the number of patients who receive eradication therapy is increasing. Although the serum level of gastrin is affected by H. pylori infection, the normal level has been unchanged for more than 20 years. The aim of this study was to study whether the present normal range for the serum gastrin level is appropriate for Japanese at present or in the near future. Methods We studied 810 adults (40–80 years old) who participated in a health survey in 2012. We measured H. pylori stool antigen, titer of serum antibody to H. pylori, and serum level of gastrin. The patient's H. pylori status was defined as positive or negative when the results of both stool antigen and serology were concordant. Subjects who were taking proton-pump inhibitor and had a previous history of gastric surgery were excluded. Results Mean serum level of gastrin was 66.2 ± 49.6 pg/mL in 281 H. pylori-negative subjects and 69.7 ± 42.2 pg/mL in 115 patients who had H. pylori eradicated at least 2 years ago. The level of gastrin was 134.4 ± 145.6 pg/mL in 224 patients with H. pylori infection and the level was significantly higher when compared with those in uninfected subjects and eradicated patients (P

A reddish depressed lesion was found in the corpus of the stomach of a 56-year-old man. Gastric biopsy showed no findings of mucosa-associated lymphoid tissue lymphoma, including lympho-epithelial lesions. A urea breath test, stool antigen test and serum IgG antibody to Helicobacter pylori test were negative. Magnifying endoscopy using narrow-band-imaging showed no malignant structures. Gastric biopsy specimens were subjected to immunohistochemistry and a polymerase chain reaction, which identified Helicobacter suis infection. Triple therapy with esomeprazole, metronidazole, and amoxicillin was administered for 10 days. Three months later, endoscopy showed the significant improvement of the lesion. H. suis infection should be considered in chronic gastritis patients without H. pylori infection.

The primary cause of osteoporosis in women is increased bone resorption and decreased bone density associated with reduced estrogen secretion. Several studies have demonstrated a relationship between Helicobacter pylori infection and osteoporosis regardless of estrogen levels. This study examined the relationship between H. pylori infection and osteopenia together with estrogen levels, calcium intake, and several lifestyle factors.This study included 473 healthy women who underwent a general health examination. Multivariate analysis was performed, with age, body mass index (BMI), smoking habit, drinking habit, exercise habit, schooling duration, estradiol levels, birth history, calcium intake, schooling duration, smoking habit, drinking habit, exercise habit, and H. pylori infection as independent variables and the presence of osteopenia as a dependent variable.The adjusted OR for osteopenia with H. pylori infection was 0.95 (95% CI 0.55-1.63, p = 0.84). In contrast, osteopenia was significantly associated with age, low BMI, lesser schooling period, low estradiol levels, and low calcium intake.H. pylori infection was not a significant risk for osteopenia by the multivariate analysis, which included the primary confounding factors. Significant factors, such as estradiol and calcium intake, should be assessed together to study the association of H. pylori infection and osteopenia.

OBJECTIVES Esophageal variceal bleeding is one of the most severe complications of liver cirrhosis, with high mortality. However, there is no established scoring system for short-term mortality in patients with esophageal variceal bleeding. The aim of this study was to evaluate the usefulness of the Glasgow-Blatchford score (GBS), the Model for End-Stage Liver Disease (MELD) score, and the Child-Pugh score for predicting short-term and hospital mortality in patients with esophageal variceal bleeding. METHODS A total of 47 patients with esophageal variceal bleeding were studied between September 2009 and March 2015. The GBS, the MELD score, and the Child-Pugh score were assessed for their ability to predict 1- and 6-week mortality rates using a receiver operating characteristic curve. RESULTS The 1- and 6-week mortality rates were 17.0 and 31.9%, respectively. The median GBS, MELD, and Child-Pugh scores were 13 (range: 4-19), 10 (range: 0-34), and 9 (range: 5-13), respectively. The GBS was superior to both the MELD and the Child-Pugh scores for prediction of 1-week mortality [area under the curve=0.82 (95% confidence interval: 0.66-0.98) vs. 0.71 (0.47-0.96) and 0.72 (0.53-0.91)]. The MELD score was superior to both the Child-Pugh score and the GBS for prediction of 6-week mortality [area under the curve=0.83 (95% confidence interval: 0.69-0.97) vs. 0.69 (0.52-0.85) and 0.67 (0.50-0.83)]. CONCLUSION For 1-week mortality, the GBS was superior to the Child-Pugh and the MELD scores in patients with esophageal variceal bleeding. However, for 6-week mortality, the MELD score was superior in patients with esophageal variceal bleeding.

An 88-year-old woman with dementia was diagnosed as having perforated emphysematous cholecystitis with localized peritonitis. Because she was at high risk for surgery, gallbladder drainage was required before surgery. Endoscopic transpapillary gallbladder drainage instead of percutaneous transhepatic biliary drainage was performed because bile could leak from the puncture site to free space around the perforated gallbladder. After the insertion of a nasobiliary drainage tube, the gallbladder was drained and cleaned with saline solution. Subsequently, a nasobiliary drainage tube was replaced with a double-pigtail stent because she was at high risk of dislodging the nasobiliary drainage tube. Although clinical improvement was observed, she was treated conservatively without surgery. She was followed up for 6 months without developing cholecystitis. For perforated cholecystitis without developing panperitonitis, endoscopic transpapillary gallbladder drainage would be an effective option as a bridge to surgery for the initial treatment and as an alternative to surgery for long-term management for a later treatment. This is the first reported case of perforated emphysematous cholecystitis with localized peritonitis treated with endoscopic transpapillary gallbladder drainage.

The aim of this study was to investigate the change in the energy metabolism and invasiveness in the perioperative period of endoscopic submucosal dissection for early gastric cancer. Fifty-two consecutive patients were enrolled into the study between July 2013 and May 2014 and examined resting energy expenditure using an indirect calorimeter, body weight and basal energy expenditure using the Harris-Benedict equation before and after endoscopic submucosal dissection. Resting energy expenditure/body weight and resting energy expenditure/basal energy expenditure were 20.2 ± 3.0 kcal/kg/day and 0.96 ± 0.11 on the day of endoscopic submucosal dissection, whereas one day after the endoscopic submucosal dissection they were 21.7 ± 3.2 kcal/kg/day and 1.03 ± 0.14, showing significant increases (p

Bortezomib is a potent proteasome inhibitor that has been extensively used to treat multiple myeloma. One of the most common grade 3 adverse events is cyclic thrombocytopenia. In this study, we studied the mechanism by which bortezomib induces thrombocytopenia in a mouse model. After the intravenous administration of bortezomib (2.5 mg/kg) via tail vein, platelet counts significantly decreased on days 2-4 and recovered to the normal range on day 6. Bortezomib (2.5 mg/kg) injected into mice in vivo did not affect colony-forming unit-megakaryocytes (CFU-Mk) or megakaryocytes in the bone marrow. However, proplatelet formation (PPF) significantly decreased on days 2 and 4, after bortezomib administration to mice. Meanwhile, CFU-Mk formation and the ploidy distribution of cultured megakaryocytes in vitro were not affected by bortezomib used at concentrations of ≤ 1 ng/mL. The PPF of megakaryocytes in vitro significantly decreased with 0.1, 1, 10, and 100 ng/mL bortezomib. Considering the bortezomib concentration in clinical studies, these data strongly suggest that decreased PPF activity induces thrombocytopenia. To elucidate the mechanism behind decreased PPF, Western blot was performed. Activated Rho expression increased after the incubation of murine platelets with bortezomib. Decreased PPF activity was eliminated by the addition of Y27632, a Rho kinase inhibitor, in vitro. Given that the Rho/Rho kinase pathway is a negative regulator of PPF, bortezomib increases activated Rho, inducing decreased PPF, which results in decreased platelet count.

A 65-year-old male was admitted for hemorrhagic gastric ulcer. Since anti-Helicobacter pylori-immunoglobulin G antibody tested positive, eradication therapy was administered using rabeprazole, amoxicillin, and clarithromycin. During hospitalization, colonoscopy showed normal colonic mucosa except for a polyp of the sigmoid colon. He was discharged 4 days after finishing eradication therapy, but fever up and diarrhea appeared on the following day. After re-admission, colonoscopy revealed multiple yellowish-white, small circular membranous elevations, and a diagnosis of pseudomembranous colitis was made. He was successfully treated by oral administration of vancomycin. Concomitant use of antibiotics and a proton pump inhibitor for a hospitalized patient is a risk for pseudomembranous colitis. However, H. pylori eradication therapy should be started at re-introduction of oral feeding in cases of bleeding ulcers because rebleeding can be mortal in patients in 'poor general condition'. Physicians should consider pseudomembranous colitis as a diagnosis for the patients with diarrhea and high fever following H. pylori eradication therapy.