[Voluntary inoculation of hepatitis B vaccine at pediatric medical institutions].

We conducted a questionnaire survey on voluntary inoculation of hepatitis B (HB) vaccine to children at 79 pediatric clinics. The voluntary vaccination rate was 65.2%, the desired vaccination target was "all infants" at 84.8% of clinics, the recommended method was "only when the patient wishes" at a rate of 80.0%, and "actively recommended" at 20.0%. If there was a request, 71.7% of clinics answered that they would like to recommend it in the future, and 38.9% said that it was difficult to recommend it because of the voluntary nature of vaccination. The requests were "expansion of the scope of regular vaccination" at 60.9% of clinics and "enlightenment activities and information provision" at 54.3%. Since it was suggested that voluntary vaccination is difficult to recommend, it is necessary to proactively provide information and public relations activities regarding its necessity to medical personnel and parents.

[Early onset of metronidazole-induced peripheral neuropathy in a patient with amoebic colitis:a case report].

Peripheral neuropathy reportedly develops after a long period of metronidazole administration. Here, we report a case of amoebic colitis in which peripheral neuropathy occurred approximately 24 hours after administering metronidazole. A 76-year-old man presented with mucous and bloody stool. Initially, lower gastrointestinal endoscopy and stool analysis confirmed the occurrence of amoebic colitis, and metronidazole was then intravenously administered. The following day, however, the patient experienced a diminished sensation in a glove-and-stocking distribution in his extremities, followed by bilateral burning foot pain. After the withdrawal of metronidazole, the symptoms improved and finally disappeared 3 months later.

[The effect of introducing an on-call system for attending physicians].

Gastroenterologists working in hospitals that have adopted the chief physician system are often required to work overtime during the night and on holidays treating critically ill patients and ordering emergency tests. To help alleviate the attending physician's duties, our hospital initiated an on-call system in October 2019 to replace the existing system. Changes in overtime hours worked and business stress before and after the introduction of the on-call system were verified. After the introduction of the on-call system, both overtime hours and the number of holidays worked decreased and work stress was reduced. We report that the on-call system is a suitable alternative to the attending physician system because it increases the work efficiency and satisfaction of attending physicians.

[Questionnaire survey on hepatitis B vaccine in clinics].

We conducted a questionnaire survey on the status of implementation of hepatitis B vaccination and HBs antibody testing. It involved medical personnel covering 484 regional medical institutions in the Osaka Province. Results showed that the recognition rate was 30.1%, the hepatitis B vaccination implementation rate was 38.9%, and that of HBs antibody testing was 38.9%. Although 42.5% of the medical institutions had experienced needle-stick injuries, some medical institutions did not respond properly. The low implementation rate of hepatitis B vaccination and HBs antibody test could be explained by lack of recognition for hepatitis B infection control guidelines. Therefore, we can achieve a possible improvement in the control of infection in the Province, if sensitization programs on hepatitis B infection control are organized in the various regional medical institutions in order to provide adequate information and raise awareness on the importance of respecting these guidelines.

[A case of cholangiolocellular carcinoma found to be hepatic hemangioma at 16-month follow up].

We report a rare case of hepatic cholangiolocellular carcinoma (CoCC) with long-term observation. A 73-year-old woman was found to have a solitary hepatic tumor with a diameter of 10mm on dynamic computed tomography (CT), which showed peripheral enhancement in the arterial phase and enhancement retention in the delayed phase. Although it was initially diagnosed as hepatic hemangioma, the follow up examination conducted 16 months later revealed that the tumor had grown to 18mm. Doubling time of the tumor was calculated to be 177 days. Because magnetic resonance imaging results were not typical for hepatic hemangioma, hepatocellular carcinoma was suspected and partial hepatectomy was performed. Histologically, the tumor was comprised dense proliferation of small irregular tubules with fibrous stroma. Immunohistochemistry revealed that the carcinoma cells were positive for cytokeratin (CK) 7, CK19, and neurnal cell adhesion molecule. Cells were negative for hepatocyte paraffin 1. Periodic acid-Schiff and Alcian blue staining showed an absence of mucin in the tumor cells, and epithelial membrane antigen was strongly positive on the luminal surface of tubules. These findings were typical of CoCC;therefore, CoCC should be ruled out when dynamic CT images suggest hepatic hemangioma.

[A case of a gas-forming liver abscess caused by Clostridium perfringens after transcatheter arterial chemoembolization].

An 80-year-old man had a medical history of chronic hepatitis C and pancreatoduodenectomy. We detected recurrence of hepatocellular carcinoma, and performed transcatheter arterial chemoembolization, instead of radiofrequency ablation or surgery, because of the patient's medical history of bile duct reconstruction and liver dysfunction. On the second day, he was diagnosed with a gas-forming liver abscess and underwent liver abscess drainage. Clostridium perfringens and sordellii were detected by aspiration and the blood culture. Meropenem and Clindamycin were administered intravenously. He was treated shortly after the occurrence before the involvement of severe hemolysis and recovered from the acute phase.

Association between endoscopic findings related to colonic diverticula and bowel habits: A multicenter study in Japan.

BACKGROUND AND AIM: Few studies have shown the associations between colonic diverticula and endoscopic findings such as location, inflammation, number of diverticula, sigmoid colon rigidity, and bowel habits. METHODS: Japanese subjects who underwent total colonoscopies at six centers in Japan from November 2015 to October 2016 were analyzed. Bowel habits were evaluated using the Gastrointestinal Symptom Rating Scale. Location and number of diverticula, inflammation, and sigmoid colon rigidity were evaluated from endoscopy results. RESULTS: A total of 762 subjects (486 men and 276 women [ratio, 1.76:1]) whose mean age was 65.5 ± 11.4 years were evaluated. In multivariate analysis, presence of constipation was associated with a significantly lower likelihood of left-sided colonic diverticula (odds ratio = 0.40, 95% confidence interval 0.20-0.82, P = 0.012), whereas right-sided and bilateral-sided colonic diverticula, multiple colonic diverticula, inflammation findings, and sigmoid colon rigidity were not related to bowel habits. CONCLUSIONS: Among endoscopic findings related to colonic diverticula and bowel habits, only left-sided colonic diverticula were inversely associated with constipation, whereas inflammation findings, multiple diverticula, and sigmoid colon rigidity were not related to bowel habits. However, the association of inflammation findings with colonic diverticula and bowel habits should be further studied. Investigation of changes in left-sided colonic diverticula may lead to new treatments for constipation.

[A case of gastrointestinal amyloidosis and hypoproteinemia improved by tocilizumab].

A woman in her 70s presented with dehydration and malnutrition due to watery diarrhea. She was examined and diagnosed with gastrointestinal amyloidosis accompanied by a protein-losing gastroenteropathy secondary to rheumatoid arthritis. She first underwent treatment with an anti-tumor necrosis factor alpha (TNF-α) antibody for secondary amyloidosis, but due to lack of adequate response, she was switched to an anti-interleukin (IL)-6 receptor antibody. Her clinical symptoms subsequently improved, and endoscopy revealed a marked decrease of amyloid protein deposits in the digestive tract. She was followed up for 3 years while continuing to receive the anti-IL-6 receptor antibody, with no recurrence. Although secondary amyloidosis is a fatal disease associated with chronic inflammatory diseases, clinical symptoms and prognosis have recently been improved by intervention with biological therapies. In particular, anti-IL-6 receptor antibodies have been reported to be superior to anti-TNF-α antibodies in the treatment of secondary amyloidosis and are expected to play a central role in treating secondary amyloidosis in the future.

[A case of disseminated carcinomatosis of bone marrow with disseminated intravascular coagulation caused by advanced colon cancer treated by mFOLFOX6].

A 45-year-old man was admitted to our hospital because of disseminated intravascular coagulation syndrome (DIC) and severe pain in his back and lumbar. Abdominal CT scan demonstrated lymph node enlargement in the whole body. FDG-PET revealed abnormal uptake of FDG in the thickening wall of the descending colon and the entire skeleton. Colonoscopy was performed continuously and revealed a poorly-differentiated adenocarcinoma of the descending colon. He was treated with the systemic chemotherapy of modified FOLFOX6 (mFOLFOX6). After one course of the treatment, DIC was resolved and severe back pain and lumbargo were improved.

Increased expression of microRNA in the inflamed colonic mucosa of patients with active ulcerative colitis.

BACKGROUND AND AIMS: MicroRNA (miRNA) are endogenous, approximately 22-nucleotide non-coding RNA that suppress gene expression at post-transcriptional levels by binding to the 3'-untranslated region of specific mRNA targets through base-pairing. It has been recently reported that miRNA have critical functions in key biological processes such as cell proliferation and cell death in various cancer cells. However, the relationship between intestinal inflammation and miRNA expression remains unclear. In the present study, we used microarray technology to identify miRNA induced in the colonic mucosa of patients with active ulcerative colitis (UC). METHODS: Two colonic biopsy specimens from patients with active stage (>Matts grade 2) of UC under colonoscopy and two colonic biopsy specimens from healthy volunteers were obtained for gene expression profiles. Total RNA was extracted, and miRNA expression profiles were investigated using miRNA Microarray. Subsequently, to confirm the result of the Microarray investigation, we checked the expression of several selected miRNA using real-time polymerase chain reaction (PCR) in 12 colonic biopsy specimens from patients with active UC under colonoscopy and 12 specimens from the healthy volunteers. RESULTS: In the microarray study, the expression of several miRNA was upregulated in the colonic mucosa of patients with active UC. Furthermore, two miRNA (miR-21, miR-155) were selected in the study using real-time PCR. CONCLUSION: Upregulated miRNA may be responsible for the development of intestinal inflammation in UC.

Familial Mediterranean Fever without Fever.

Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease commonly observed around the Mediterranean basin presenting as recurrent febrile episodes. We herein describe a Japanese case of genetically-confirmed FMF, in which fever was lacking during attacks. An otherwise healthy 34-year-old man presented with frequent episodes of abdominal pain, which resolved spontaneously. During the attacks, the patient was afebrile, but the inflammatory marker levels in his blood were increased. Abdominal CT demonstrated enhancement of the jejunal membrane. After the initiation of colchicine therapy, the patient experienced no attacks for more than one year. The diagnosis of FMF was confirmed by a genetic analysis.

Synergistic effect of HLA class II loci and cytokine gene polymorphisms on the risk of gastric cancer in Japanese patients with Helicobacter pylori infection.

It has been reported that polymorphisms of human leukocyte antigen (HLA) genes and several cytokine genes are associated with an increased risk of developing gastric cancer (GC). However, the results of studies from different geographic regions, ethnic groups and study groups are inconsistent. The aim of this study was to evaluate the influence of H. pylori infection and host genetic factors on GC susceptibility in Japanese patients with GC. We analyzed genotypes for HLA class I and II, tumor necrosis factor alpha, interleukin (IL)-1beta, IL-1 receptor, IL-4, IL-4Ralpha and IL-10 in 330 H. pylori-infected noncardia patients with GC and 190 H. pylori-infected nonulcer dyspeptic controls. Haplotype analyses indicated that the frequencies of the HLA DRB1*0405 and DQB1*0401 alleles were increased in the patients with intestinal-type GC when compared with controls (both DRB1*0405 and DQB1*0401: p = 0.015, OR = 1.57, 95% CI = 1.09-2.26), but the changes were not statistically significant after correction for multiple comparisons. None of the cytokine gene polymorphisms were associated with GC susceptibility, whether patients with GC were analyzed as a group according to the histological subtype. Of interest was the comparison of controls and patients with intestinal-type GC. The frequency of an IL-10-592AA homozygote showing concomitant carriage of the HLA DRB1*0405-DQB1*0401 haplotype was significantly higher in patients with intestinal-type GC (chi(2) = 6.369, p = 0.0116, p(c) = 0.0464, OR = 2.43, 95% CI = 1.21-4.48). Our results suggest that the HLA class II and IL-10-592A/C polymorphisms synergistically affect the susceptibility to GC development of H. pylori-infected individuals in the Japanese population.

[A case of inflammatory myofibroblastic tumor of the lesser omentum with intratumoral hemorrhage].

A 24-year-old man presented complaining of epigastralgia and tenderness in the epigastric region. An abdominal computed tomography revealed a low density tumor, extending between the anterior wall of the stomach and the abdominal wall. Because the tumor was found to enlarge, an operation was performed to remove the tumor. During the operation, it was revealed that the tumor was connected with the lesser omentum, which suggested that it had originated from the lesser omentum. We diagnosed an inflammatory myofibroblastic tumor based on the pathological examination, which revealed infiltration of inflammatory cells, sparse proliferation of spindle cells and limited proliferation of collagen fibers, characterized by an irregular arrangement.

[A case of advanced gastric cancer with pulmonary carcinomatous lymphangitis responding remarkably to combination chemotherapy of docetaxel, CDDP and S-1].

A 31-year-old woman suffering from stomach pain was admitted to our hospital, and diagnosed with unresectable advanced gastric cancer. She was initially treated with combination therapy of S-1 and CDDP, and a partial response was achieved. After two courses of the chemotherapy, however, she complained of dyspnea, and pulmonary carcinomatous lymphangitis was confirmed by computed tomography. As second-line chemo-therapy, we attempted combination therapy with docetaxel, CDDP and S-1(DCS). After one course of the combination therapy, a remarkable response in the pulmonary carcinomatous lymphangitis was achieved. Treatment of patients with advanced gastric cancer associated with pulmonary carcinomatous lymphangitis is quite difficult and there is no scientific evidence to select anti-cancer drugs for these patients. We concluded that DCF could be a useful regimen for patients with gastric cancer associated with pulmonary carcinomatous lymphangitis.

CV-11974, angiotensin II type I receptor antagonist, protects against ischemia-reperfusion injury of the small intestine in rats.

BACKGROUND: Angiotensin II has been implicated in the pathogenesis of vascular inflammation in various organs. The aim of the present study was to examine the effect of angiotensin II type I receptor antagonist, CV-11974, on reperfusion-induced small intestinal injury in rats. METHODS: Intestinal damage was induced by clamping both the superior mesenteric artery and the celiac trunk for 30 min followed by reperfusion for 60 min in male Wistar rats. CV-11974 was given to the rats by intravenous injection 1 h before the vascular clamping. The intestinal mucosal injury and inflammation were evaluated by biochemical markers and histological findings. Thiobarbituric acid reactive substances and tissue-associated myeloperoxidase (MPO) activity were measured in the gastric mucosa as indices of lipid peroxidation and neutrophil infiltration. The expressions of pro-inflammatory cytokines (CINC-1) in intestinal mucosa were measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-PCR (RT-PCR). In additional experiments with an in vitro flow system, human neutrophils were perfused on human umbilical vein endothelial cells (HUVEC) pretreated with anoxia-reoxygenation with or without CV-11974 and then the adhesive neutrophils were counted. RESULTS: Reperfusion after ischemia resulted in an increase in luminal protein concentrations, hemoglobin concentrations, thiobarbituric acid reactive substances, and MPO activity. Pretreatment with CV-11974 significantly inhibited the increases in these parameters. CV-11974 also inhibited increases in intestinal CINC-1 protein and mRNA expression induced by ischemia-reperfusion. Moreover, in an in vitro study, CV-11974 significantly inhibited the adherence of neutrophils to HUVEC exposed to reoxygenation after anoxia. CONCLUSIONS: These results suggest that the blockade of angiotensin II type I receptor by treatment with CV-11974 remarkably reduced the reperfusion-induced intestinal injury.

Effect of a novel water-soluble vitamin E derivative as a cure for TNBS-induced colitis in rats.

Lipid peroxidation mediated by oxygen free radicals plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Vitamin E is a lipid-soluble antioxidant and is generally considered to protect against lipid peroxidation of the cell membrane and to scavenge singlet oxygen and superoxide anion radical. Therefore, vitamin E or its derivatives are expected to have particular application for patients suffering from IBD. The aim of this study was to investigate the antioxidative effects of the water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetra-methylchroman-6-ol(TMG), on the therapy of experimental colitis in rats. Colitis was induced in male Wistar rats weighing 200 g using an enema of trinitrobenzene sulfonic acid (TNBS) dissolved in 50% ethanol; TMG dissolved in physiological saline was injected intra-peritoneally every day from 24 h after the enema of TNBS. The damage score, wet weight of the colon, and increase in body weight were estimated 1 week after the enema of TNBS. Thiobarbituric acid-reactive substances (TBA-RS), an index of lipid peroxidation, and tissue-associated myeloperoxidase (MPO) activity in the colonic mucosa were measured 1 week after the induction of colitis. As a result, increase in body weight was inhibited by the induction of colitis, although the inhibition was reduced in the group treated with TMG. The damage score, wet weight, TBA-RS and MPO activity were increased significantly in the colitis group; however, they were inhibited by the administration of TMG. These results suggest that TMG is effective for the treatment of colitis in rats induced by TNBS. In the future, TMG could be a new therapeutic agent for IBD.

Rosuvastatin, a new HMG-CoA reductase inhibitor, reduces the colonic inflammatory response in dextran sulfate sodium-induced colitis in mice.

The aim of the present study was to elucidate the beneficial effects of rosuvastatin, a new HMG-CoA reductase inhibitor, on colonic mucosal damage and on the inflammatory response in a dextran sulfate sodium (DSS) colitis model. Acute colitis was induced using 8% DSS in female BALB/c mice. Colonic mucosal inflammation was evaluated clinically, biochemically, and histologically. Mucosal protein contents and mRNA levels of tumor necrosis factor (TNF)-alpha were determined by immunoassay and real time-PCR. The mRNA levels of endothelial nitric oxide synthase (eNOS) were determined by real-time PCR. Disease activity scores in DSS-induced colitis model mice, as determined by weight loss, stool consistency, and blood in stool, were significantly lower in the rosuvastatin-treated mice than in control mice. Shortening of the colon was significantly reversed by rosuvastatin. Increases in tissue-associated myeloperoxidase activity and thiobarbituric acid-reactive substances after DSS administration were both significantly inhibited by treatment with rosuvastatin. Rosuvastatin also inhibited increases in intestinal TNF-alpha protein and mRNA expression after DSS administration, respectively. The mucosal mRNA levels of eNOS were decreased after DSS administration, but preserved in mice treated with rosuvastatin. These results suggest that rosuvastatin prevents the development of DSS-induced colitis in mice via the inhibition of mucosal inflammatory responses associated with the preservation of eNOS transcription.

A novel water-soluble vitamin E derivative protects against aspirin-induced gastric mucosal injury in rats.

Oxygen radical-mediated lipid peroxidation and neutrophil activation may be involved in the development of gastric mucosal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs). Vitamin E is one of the lipid-soluble antioxidants and is generally considered to protect against lipid peroxidation of the cell membrane and to scavenge singlet oxygen and superoxide anion radicals. Our object was to investigate the antioxidative effects of water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetra-methylchroman-6-ol (TMG), on aspirin-induced gastric mucosal injury in rats. Gastric injury was induced by intragastric administration of aspirin and 0.15 N HCl in male Sprague-Dawley rats. TMG dissolved in physiological saline was injected intraperitoneally 0.5 h before the aspirin administration. The intragastric administration of acidified aspirin induced hyperemia and hemorragic erosions in rat stomach. The increase in total area of gastric erosions was reduced by pretreatment with TMG in a dose-dependent manner. The increases of thiobarbituric acid-reactive substances (TBA-RS) and myeloperoxidase (MPO) activity 3 h after aspirin administration were significantly inhibited by pretreatment with TMG. The gastric concentration of cytokine-induced neutrophil chemoattractants-1 (CINC-1) increased after aspirin administration, and the increase was also inhibited by pretreatment with TMG. These results suggest that TMG is effective for the treatment of aspirin-induced gastric injury. This anti-inflammatory effect of TMG seems to be related to impairment of lipid peroxidation, neutrophil function and cytokine production in gastric mucosa.

Edaravone, a newly developed radical scavenger, protects against ischemia-reperfusion injury of the small intestine in rats.

Although edaravone (3-methyl-1-phenyl-pyrazolin-5-one), a newly developed radical scavenging agent, has been widely used for protection against ischemia-reperfusion (I-R) injury in patients with cerebral infarction, its effects on gastrointestinal I-R injury have not been evaluated. In the present study, we examined the effects of edaravone on experimental intestinal I-R damage in rats. In male Wistar rats with and without edaravone treatment, intestinal damage was induced by clamping the superior mesenteric artery for 30 min, followed by reperfusion. Edaravone was administered via intravenous infusion at 5 min before reperfusion was achieved by removal of the clamp. The rats were sacrificed after 60 min of reperfusion. Luminal protein and hemoglobin concentrations were measured as an index of mucosal injury and histological examination of hematoxylin and eosin-stained sections was performed. Thiobarbituric acid (TBA)-reactive substances and tissue-associated myeloperoxidase (MPO) activity were measured in the mucosa as indicators of lipid peroxidation and neutrophil infiltration, respectively. The mucosal concentration of cytokine-induced neutrophil chemoattractant (CINC)-1 (a member of the IL-8 family) was determined by enzyme-linked immunosorbent assay (ELISA). Additionally, CINC-1 messenger RNA (mRNA) was measured by the reverse-transcription polymerase chain reaction (RT-PCR). As a result, the levels of luminal protein and hemoglobin, TBA-reactive substances, and MPO activity were all increased significantly by I-R injury, and these increases were significantly inhibited by treatment with edaravone. Multiple erosions and bleeding were observed macroscopically after the small intestine was exposed to I-R injury, and these changes were inhibited by administration of edaravone. Microscopic I-R damage was also reduced by treatment with edaravone. CINC-1 protein and CINC-1 mRNA were both increased by I-R injury, while edaravone markedly reduced the levels of both protein and mRNA. In summary, these results suggest that edaravone can protect the small intestine against I-R injury by scavenging oxygen-derived free radicals.

Rotenone, a mitochondrial electron transport inhibitor, ameliorates ischemia-reperfusion-induced intestinal mucosal damage in rats.

In ischemia-reperfusion (I/R)-induced tissue injury, oxygen radicals can be generated by several mechanisms. One of the important sources of oxygen radicals is thought to be mitochondrial respiration. The aim of this study was to investigate the antioxidative defense effect of the mitochondrial electron transport inhibitor, rotenone using the I/R-induced rat intestinal mucosal injury model in vivo. Intestinal ischemia was induced for 30 min by applying a small clamp to the superior mesenteric artery in rats. Rotenone at a dose of 100 mg/kg was given to rats orally 2 h before the ischemia. Intraluminal hemoglobin and protein levels, the mucosal content of thiobarbituric acid-reactive substances (TBARS), the mucosal myeloperoxidase activity, and the content of inflammatory cytokines (CINC-1, TNF-alpha) were all significantly increased from mean basal levels after 60 min of reperfusion. These increases after I/R were inhibited by treatment with rotenone at a dose of 100 mg/kg. Co-administration with succinate (100 mg/kg), a substrate of the mitochondrial electron transport system, cancelled significant reduction of intraluminal hemoglobin and mucosal TBARS treated with rotenone alone. The results of the present study indicate that rotenone inhibited lipid peroxidation and reduced development of the intestinal mucosal inflammation induced by I/R in rats. This investigation suggests that rotenone has potential as a new therapeutic agent for reperfusion injury.