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Background: Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance. Some patients with PJS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood and sometimes have serious complications that significantly reduce their quality of life. Hamartomatous polyps in the small bowel may cause bleeding, intestinal obstruction, and intussusception. Novel diagnostic and therapeutic endoscopic procedures such as small-bowel capsule endoscopy and balloon-assisted enteroscopy have been developed in recent years. Summary: Under these circumstances, there is growing concern about the management of PJS in Japan, and there are no practice guidelines available. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour and Welfare with specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of PJS together with four clinical questions and corresponding recommendations based on a careful review of the evidence and involved incorporating the concept of the Grading of Recommendations Assessment, Development and Evaluation system. Key Messages: Herein, we present the English version of the clinical practice guidelines of PJS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with PJS.

Here, we present a comprehensive study on atomic-scale in-situ biasing/heating scanning transmission electron microscopy ((S)TEM) of Al-amorphous SiO2–SiC interface. The investigation includes electrical, chemical, and structural analysis of the interface at different temperatures (25–600 °C). The results show that at ~ 500 °C the electrical (three-orders of magnitude resistivity drop), chemical (dissolution of SiO2 amorphous layer), and microstructural features (e.g. formation of Al2O3, Si and Al4C3) of the interface start to change. According to the results, amorphous SiO2 dissolves in Al, leading to formation of α-Al2O3 and Si within the Al. In contrast, elemental interdiffusion (Al3+ ⇄ Si4+) between Al and SiC occurs resulting in formation of Al4C3. From the results, we can infer that reaction mechanism between Al and crystalline SiC is different with that between Al and SiO2 amorphous phase. It is believed that structural similarities between SiC and Al4C3 play an important role in paving the way for elemental interdiffusion.

Primary eosinophilic gastrointestinal disorders (EGIDs) constitute chronic allergic inflammation. The number of eosinophils is one of the diagnostic criteria; more than 20 eosinophils per high-power field (HPF) in the gastrointestinal (GI) tract are considered abnormal in Japan. However, the quantity of eosinophils considered normal varies according to anatomical location and geographical region; such values have not been reported in Japanese pediatric patients, nor have the numbers of lymphocytes in the normal pediatric stomach. To establish a reference for defining diagnostic criteria for EGIDs, we evaluated the number of eosinophils in the normal Japanese pediatric GI tract.We examined 131 biopsy cases without significant clinical history, endoscopic abnormality, or histological abnormality. Immunohistochemical analysis of CD3 and CD20 was performed.The mean eosinophil density was highest in the cecum (49.5 ± 22.4 per HPF). Counts of more than 20 eosinophils per HPF were observed in the duodenum [bulb (20.0 ± 9.6) and second portion (30.0 ± 15.8)], terminal ileum (38.3 ± 22.7), cecum (49.5 ± 22.4), ascending colon (42.3 ± 25.3), transverse colon (29.4 ± 17.0), and descending colon (32.2 ± 17.9). Counts of fewer than 10 eosinophils per HPF were observed in the stomach and rectum; a count of fewer than one eosinophil per HPF was observed in the esophagus. More than 100 CD3-positive T cells per HPF were observed in the stomach.The mean numbers of eosinophils in the bowel were greater than 20 per HPF. For Japanese pediatrics, the current threshold eosinophil count should be revised.

This report describes a rare horizontal transmission of hepatitis B virus (HBV) from an unvaccinated 6-year-old boy to his father. The father had been diagnosed with acute hepatitis B 1 month earlier; therefore, when the child visited the clinic with fever, he was screened for HBV markers and diagnosed as an asymptomatic carrier. Neither the child nor his father was vaccinated against HBV, whereas the child’s mother and sister, having received the HBV vaccination as they were medical staff and a nursing student, respectively, tested negative for the hepatitis B surface antigen (HBsAg) and positive for anti-HBs. We performed a phylogenetic analysis of HBV in the child and his father, and identified 100% homologous strains of identical genotype C. At diagnosis, the father tested positive for IgM anti-hepatitis B core with a high titer, whereas the child tested negative for this marker. These data strongly indicated a child-to-father transmission. In this case, the HBV infection route was speculated as close contact including saliva-based transmission between the child and father, mainly attributed to their daily food habits. When clinicians diagnose patients with acute or chronic HBV infection, the household members should have been examined for HBV markers immediately. If some household members are susceptible to HBV infection, all members should be vaccinated against HBV.

BACKGROUND AND AIM We retrospectively determined the safety and efficacy of the endoscopic delivery (ED) of capsule endoscopes. METHODS We enrolled 10,156 patients who underwent small bowel capsule endoscopy (SBCE), 3182 who underwent patency capsule (PC), and 1367 who underwent colon capsule endoscopy (CCE), at 11 gastroenterological and nine pediatric centers. RESULTS Small bowel capsule endoscopies, PCs, and CCEs were endoscopically delivered to 546 (5.4%), 214 (6.7%), and 14 (1.0%) patients, respectively. Only mild complications occurred for 21.6% (167/774), including uneventful mucosal damage, bleeding, and abdominal pain. Successful ED of SBCE to the duodenum or jejunum occurred in 91.8% and 90.7% of patients aged

Capsule endoscopy (CE) and balloon-assisted enteroscopy (BAE) have become indispensable techniques for the diagnosis and management of small bowel disease in both adult and pediatric cases. However, relevant differences exist in the indications between these cohorts, with body weight and age having particular relevance in decisions for the latter. Both CE and BAE are designed for adult physique and they were not widely used among children. In addition, the types of small intestinal diseases differ between adults and children, and consequently, the indications also differ between them. This review focuses on the issues relevant to pediatric cases and describes the practical application of endoscopy in clinical practice. In conclusion, although there are age and weight restrictions, both CE and BAE are safe and useful devices for use in children, and their indications for use in children are likely to expand in the future.

BACKGROUND Although the prevalence of gastroesophageal reflux disease (GERD) has been increasing in Japan, little is known about the prevalence and severity of GERD in pediatric patients. This study compared the prevalence and severity of endoscopically proven GERD in pediatric patients seen at an endoscopy center in Japan over a 15-year period. METHODS This was a retrospective chart review of Japanese children aged 5-18 years undergoing esophagogastroduodenoscopy for upper gastrointestinal symptoms or anemia between 2005 and 2019. The prevalence and severity of reflux esophagitis and endoscopic Barrett's esophagus were compared between the periods 2005-2012 and 2013-2019. RESULTS A total of 564 patients were evaluated: 315 from 2005 to 2012 (mean ± SD) age 13.8 ± 3.0 (range, 5-18 years; 147 boys; and 249 from 2013 to 2019 (mean ± SD) 14.7 ± 2.8 (range, 5-18) years; 108 boys. Demographics and clinical features were similar between the two groups. The proportion with erosive esophagitis or endoscopic Barrett's esophagus increased significantly between the two periods (9.8% to 18.1% for GERD, P = 0.0045 and 2.5% to 9.6% for Barrett's esophagus, P = 0.0003). The proportion of GERD patients with endoscopic Barrett's esophagus also significantly increased between the two periods (24/45 [53.3%]) vs (8/31 [25.8%]), P = 0.017]. CONCLUSION The prevalence and severity of endoscopically proven GERDs has significantly increased over the past 15 years at an endoscopy center in Japan. Detailed population-based studies are needed to assess whether this is occurring throughout Japan.

Objectives Causes of early-onset refractory diarrhea include exudative diarrhea associated with very early-onset inflammatory bowel diseases, osmotic or secretory diarrhea, and protein-losing enteropathy. Monogenic disorders are included in these diseases, yet a comprehensive genetic analysis has not been fully established. Methods We established targeted gene panels covering all responsible genes for early-onset diarrhea. In total, 108 patients from 15 institutions were enrolled in this study. We collected clinical data from all patients. Seventy-three patients with exudative diarrhea, 4 with osmotic or secretory diarrhea and 8 with protein-losing enteropathy were subjected to genetic analysis. Results A total of 15 out of the 108 enrolled patients (13.9%) were identified as monogenic. We identified 1 patient with RELA, 2 with TNFAIP3, 1 with CTLA4, 1 with SLCO2A1, 4 with XIAP, 3 with IL10RA, 1 with HPS1, 1 with FOXP3, and 1 with CYBB gene mutations. We also identified 1 patient with NFKB2 and 1 with TERT mutations from the gene panel for primary immunodeficiency syndromes. The patient with refractory diarrhea caused by heterozygous truncated RelA protein expression is the first case identified worldwide, and functional analysis revealed that the mutation affected nuclear factor kappa B signaling. Genotypes were significantly associated with the clinical and pathological findings in each patient. Conclusions We identified variable monogenic diseases in the patients and found that genes responsible for primary immunodeficiency diseases were frequently involved in molecular pathogenesis. Comprehensive genetic analysis was useful for accurate molecular diagnosis, understanding of underlying pathogenesis, and selecting the optimal treatment for patients with early-onset refractory diarrhea.An infographic for this article is available at: http://links.lww.com/MPG/B853.

The first guidelines for care of pregnant women carrying the hepatitis C virus (HCV) and their infants were published in 2005 in Japan. Since then, evidence has gradually accumulated worldwide regarding the natural course and treatment of this condition and, especially in recent years, treatment for chronic hepatitis C in adult patients has made great progress. However, the clinical practice policy for children has not been standardized, and new clinical practice guidelines for children with mother-to-child (MTC) transmitted HCV infection have become necessary.In the development of the current guideline, we requested cooperation from The Japanese Society for Pediatric Infectious Diseases, The Japan Society of Hepatology, and the Japan Society of Obstetrics and Gynecology. The committee members were recommended and approved by each society to participate in developing the guidelines. The guideline was also created in accordance with the Minds Guide for Practice Guideline Development. The statements were prepared by consensus-building using the Delphi method, based on the comprehensively searched academic papers and guidelines. These articles were retrieved through searching the PubMed, Cochrane Library, and the Igaku Chuo Zasshi databases.Eight clinical questions (CQs) with clinical statements were developed regarding etiology (CQs 1-3), diagnosis (CQs 4 and 5), and treatment (two CQs 6 and 7). In each statement, the consensus rate, evidence level, and recommendation level were determined.The guidelines will be helpful in the management of children with hepatitis C MTC transmission.

Backgrounds Eosinophilic gastrointestinal disorders (EGID) are a group of conditions with increased eosinophilic infiltration in any part of the gastrointestinal tract. Although an allergic reaction to certain foods is considered the main cause of EGID, their detailed pathomechanism has not yet been elucidated, nor have proper management strategies been fully established. Moreover, some patients with intractable EGID are resistant to such therapies as an empirical elimination diet and corticosteroids. Methods We retrospectively analyzed the medical records of 4 children with intractable eosinophilic gastroenteritis (EGE) managed with elemental diet therapy (EDT) using an amino acid-based formula. Results All patients displayed resolution of their symptoms after 2 weeks of EDT. Three patients successfully completed food reintroduction and could return to their normal life. No adverse events related to EDT were recorded. Conclusions EDT appears effective and safe for treating pediatric intractable EGE symptoms. Afterwards, the patient's dietary habits should be considered during carefully monitored food reintroduction. With the relatively small number of published case reports and no randomized trials, more study is needed on EDT for EGE.

Several basic researches have indicated that there is a significant relationship between bile reflux and the pathogenesis of Barrett’s esophagus (BE). However, only few clinical studies have been reported regarding the endoscopic finding of bile reflux and Barrett’s esophagus. Our objective is to evaluate whether the endoscopic evidence of bile reflux is an independent factor associated with the presence of BE. Methods We conducted a retrospective analysis of a prospectively maintained database comprised of consecutive Japanese patients who underwent screening gastroscopy. Endoscopic findings of BE, reflux esophagitis, atrophic gastritis and sliding hernia were recorded. Evaluation of a BE was based on the Prague criteria. Endoscopic evidence of bile reflux was defined as the presence of yellow or green juice observed by white light image or red juice by narrow band image (NBI) in the gastric fundus. Univariate and multivariate analyses were performed to identify factors that differed significantly between patients with or without BE. Results A total of 454 patients were enrolled; 124 (27%) had BE and 126 (28%) had endoscopic evidence of bile reflux. Compared to patients without BE, patients with BE were more likely to be old, male and to have sliding hernia and endoscopic evidence of bile reflux on univariate analysis. On multivariate analysis, endoscopic evidence of bile reflux was a stronger independent factor associated with BE (odds ratio(OR) 11.3, 95% confidence interval(CI) 6.56–19.4) compared to the presence of sliding hernia (OR 3.58, 95%CI 2.14–6.0). Conclusion Endoscopic evidence of bile reflux identified by white light or NBI is a strong independent factor associated with the presence of BE, implying that this finding should be considered as an important parameter to determine the surveillance strategy for gastroesophageal reflux disease patients same as the presence of sliding hernia.

BACKGROUND Nodular gastritis is most often one of the manifestations of Helicobacter pylori (H. pylori) infection, which is a risk factor for gastric cancer. This study aimed to determine if the histological characteristics of nodular gastritis differed across classes of age. METHODS We conducted a retrospective analysis of consecutive patients who had undergone esophagogastroduodenoscopy with multiple mucosal biopsies of the stomach between 2003 and 2019 for evaluation of updated Sydney System scores. We analyzed and compared the histological characteristics of pediatric (≤15 years old), young (16-29 years old), and older (≥30 years old) patients. RESULTS Of the 1321 patients enrolled, 1027 patients (78%) had H. pylori infection, with 214 patients (21%) of them displaying nodular gastritis. Among nodular gastritis patients, mononuclear cell infiltration Sydney System scores in the gastric body were significantly higher in the older group than in the pediatric (p

Objectives This multicenter, cross-sectional study aimed to elucidate the efficacy and safety of the AdvanCE capsule endoscope delivery device for children in Japan. Methods The present study analyzed 183 cases of small bowel capsule endoscope (SBCE) insertion performed using the AdvanCE in 154 patients aged less than 18 years at participating institutions between 2013 and 2017. Statistical analyses were conducted to identify factors contributing to the completion rate for the entire small intestine examination, small intestine transit time, adverse events and technical issues. Results The commonest reason for using the AdvanCE was the patient's inability to swallow the SBCE, which was attributed to young age. SBCE was successfully delivered into the stomach or duodenum in 180 cases and was placed in the duodenum in 90% patients. In 89% patients, the entire small intestine was completely examined, and in 63% patients, findings leading to a new diagnosis or involving changing or maintaining the treatment strategy were obtained. No severe adverse events were observed; however, mild adverse events were observed in 35% patients. No factors considerably contributed to the completion rate for the entire small intestine examination or small intestine transit time and onset of technical issues. The factors that contributed to mild adverse events included intravenous anesthesia, technical issue, and absence of prior insertion of a patency capsule using the AdvanCE. Conclusion The AdvanCE is well tolerated and effective for children.

The benefit of balloon-assisted enteroscopy (BAE) had been recently documented in pediatric patients, but previous reports are based on single institution experiences. We evaluated the feasibility of pediatric BAE in 8 tertiary referral hospitals throughout Japan.This was a prospective, multi-institutional study. Patients younger than 18 years were enrolled between April 2014 and March 2017 to undergo double-balloon or single-balloon enteroscopy. Data were collected prospectively using a standardized questionnaire.We enrolled 79 pediatric patients (96 procedures, 70 boys, 26 girls; median age 12.7 years, range 1-17 years). Antegrade (oral-route) BAE was performed in 20 procedures (lowest body weight 12.9 kg, youngest age 3.7 years), and retrograde (anal-route) BAE in 76 (lowest body weight 10.8 kg, youngest age 1.6 years). Severe adverse events were associated with BAE in 2 patients: 1 with hemorrhage due to polypectomy and 1 with pancreatitis after double-balloon endoscopic retrograde cholangioscopy. No intestinal perforation was reported. Procedure duration of oral-route BAE for diagnosis was significantly longer than anal-route for diagnosis (P 0.001). The overall diagnostic yield for rectal bleeding/positive fecal occult blood test and abdominal pain was 48%. Among 40 patients referred for diagnosis who did not undergo capsule endoscopy, diagnoses were confirmed in 17 (42.5%) patients after BAE.This prospective multicenter observational study documents the efficacy of BAE in pediatric patients.

Hereditary colorectal cancer (HCRC) accounts for

A 13-year-old girl presented with sudden-onset colicky abdominal pain and biliary vomiting. She was diagnosed with Peutz-Jeghers syndrome 2 months previously based on mucocutaneous pigmentation and hamartomatous polyposis. On diagnosis of Peutz-Jeghers syndrome, in addition to colonoscopy and esophagogastroduodenoscopy, antegrade and retrograde double-balloon enteroscopies were performed, and >10 hamartomas were resected. She was scheduled for additional elective double-balloon enteroscopy for total small-bowel observation. On visiting the emergency unit, enhanced abdominal computed tomography showed jejuno-jejunal intussusception with a polyp. There were no ischemic signs in the invaginated bowel. Urgent antegrade double-balloon enteroscopy performed 5 hours after onset of acute abdominal symptoms revealed a large polyp with intussusception stalk in the jejunum, and simultaneous reduction of intussusception and endoscopic mucosal resection of the polyp were performed successfully. There were no endoscopy-related complications, and emergent laparotomy was avoided. The patient has been asymptomatic, and total gastrointestinal screening is scheduled every 2 years. This is the first case in which emergent laparotomy was avoided by urgent double-balloon enteroscopy in an adolescent with symptomatic jejuno-jejunal intussusception. Non-surgical management of small-bowel polyps in pediatric patients with Peutz-Jeghers syndrome is beneficial as laparotomy can cause bowel adhesion and increases risk of incomplete balloon-assisted enteroscopy.

This report describes a rare horizontal transmission of hepatitis B virus (HBV) from an unvaccinated 6-year-old boy to his father. The father had been diagnosed with acute hepatitis B 1 month earlier; therefore, when the child visited the clinic with fever, he was screened for HBV markers and diagnosed as an asymptomatic carrier. Neither the child nor his father was vaccinated against HBV, whereas the child's mother and sister, having received the HBV vaccination as they were medical staff and a nursing student, respectively, tested negative for the hepatitis B surface antigen (HBsAg) and positive for anti-HBs. We performed a phylogenetic analysis of HBV in the child and his father, and identified 100% homologous strains of identical genotype C. At diagnosis, the father tested positive for IgM anti-hepatitis B core with a high titer, whereas the child tested negative for this marker. These data strongly indicated a child-to-father transmission. In this case, the HBV infection route was speculated as close contact including saliva-based transmission between the child and father, mainly attributed to their daily food habits. When clinicians diagnose patients with acute or chronic HBV infection, the household members should have been examined for HBV markers immediately. If some household members are susceptible to HBV infection, all members should be vaccinated against HBV.

We fabricated successfully heterostructures of AlGaN/GaN and AlGaN/InGaN/GaN on AlN template/c-sapphire exhibiting the Shubnikov-de Haas (SdH) oscillation in the magnetic field at lower temperatures. In AlxGa1-xN/GaN system, the carrier density of two-dimensional electron gas (2DEG) was controlled from 4.0 × 1012 to 9.0 × 1012 cm−2, which was consistent with the theoretical simulation, with increase of Al composition in AlGaN barrier layer. In AlGaN/InGaN/GaN system, the surface morphology and alloy disorder on the InGaN were properly defined. The effective mass of 2DEG at the Al0.22Ga0.78N/In0.04Ga0.96N interface was estimated to be 0.24 m0 from the temperature dependence of SdH oscillation amplitude. Although the effective mass was comparable to that of AlGaN/GaN heterostructure, the mobility of 2DEG at the InGaN was drastically degraded in spite of the slight amount of indium incorporation. This reduction was attributed to larger scattering probably due to the interface roughness of InGaN layer caused by the step meandering and/or the potential fluctuation caused by random incorporation of indium atoms.

Human intestinal spirochetosis (HIS) is a condition in which spirochetes attach to and colonize the colorectal epithelium. To our knowledge, no comprehensive studies of HIS in young patient have been published in a developed country. This study aimed to determine the incidence and clinicopathological manifestations of HIS in Japanese patients aged less than 20 years. We retrospectively reviewed 3605 biopsy and 92 surgical specimens obtained from 479 patients admitted to Shinshu University Hospital between 1997 and 2014. All slides were reviewed independently by two pathologists to confirm the histological presence of spirochetes. Among 387 patients who underwent biopsy, the most common pathologic diagnosis was ulcerative colitis (12.6%, n = 49). Additionally, about half of the biopsy specimens showed non-specific, mildly inflamed mucosa (50.6%, n = 196); only one of these cases was HIS. On the other hand, among the surgical specimens, we found no cases of HIS. We concluded that the incidence of HIS in Japanese young patients was 0.2% (1/479 cases). The incidence of HIS in Japanese young patients was very low, and one HIS case was associated with colitis with abdominal pain.

Background and Aim Western studies have suggested two distinct etiologies of esophagogastric junction (EGJ) cancer: Helicobacter pylori-associated atrophic gastritis and non-atrophic gastric mucosa resembling esophageal adenocarcinoma. The present study investigated whether endoscopic gastric mucosal atrophy can distinguish between these two types of EGJ adenocarcinoma. Methods Data were collected from patients with Siewert type II, T1 EGJ adenocarcinoma who underwent endoscopic or surgical resection at eight Japanese institutions in 2010–2015. Clinicopathological characteristics of EGJ cancers with and without endoscopic gastric mucosal atrophy were compared. EGJ was defined as the lower end of the palisade vein and/or the top of the gastric folds. Results Of the 229 patients identified, 161 had endoscopic gastric mucosal atrophy and 68 did not. The latter group was younger (64 vs 70 years, P = 0.000); had a higher proportion of patients negative for H. pylori (90% vs 47%, P

Pediatric inflammatory bowel disease (IBD) is a heterogeneous disorder caused by multiple factors. Although genetic and immunological analyses are required for a definitive diagnosis, no reports of a comprehensive genetic study of a Japanese population are available. In total, 35 Japanese patients

Intussusception is a frequent and severe complication of Peutz–Jeghers syndrome (PJS). We herein present the case of a 3-year-old girl who experienced jejuno-jejunal intussusception due to PJS polyps. Despite no apparent family history of PJS, she had exhibited mucocutaneous pigmentation since infancy and recurrent abdominal pain and vomiting from 2 years of age. Segmental resection of the jejunum during emergency laparotomy for the intussusception revealed multiple hamartomatous polyps. Genetic analysis uncovered a germline nonsense mutation of c.247A>T in exon 1 of serine/threonine kinase 11 (STK11). Biannual follow-up surveillance for polyps by esophagogastroduodenoscopy, colonoscopy, and small bowel capsule endoscopy is ongoing. Reports describing the clinical and genetic features of extremely young PJS with intussusceptions are rare, although a literature review of STK11 germline mutations revealed several other pediatric cases of complicating intussusception at ≤ 8 years old. Considering the recent advances in surveillance and treatment options for the small bowel, earlier management of symptomatic children with PJS may be warranted to avoid surgical emergency.

BACKGROUND Previously, we conducted an epidemiological study screening for Helicobacter pylori antibody positivity among Japanese junior high school students. In this study, we updated the epidemiological data and assessed the clinical features of H pylori antibody-positive junior high school students. MATERIALS AND METHODS We assessed H pylori antibody-positive subjects who were identified between 2012 and 2015 at four junior high schools in Nagano Prefecture, Japan. H pylori infection was confirmed by urea breath test (UBT) or endoscopic examination. Endoscopy was performed after obtaining consent from the subject and their guardians. Eradication therapy consisted of triple therapy with proton pump inhibitor (PPI), amoxicillin (AMPC), and clarithromycin (CAM) or metronidazole (MNZ) for seven days. Eradication of H pylori was confirmed by UBT. We reviewed subjects' characteristics, endoscopic findings, histological findings, eradication regimes, outcomes, and adverse effects. RESULTS The overall prevalence of H pylori antibody positivity was 3.2% (42/1298). We assessed thirteen H pylori antibody-positive subjects. Eight subjects had a family history of H pylori infection. Six subjects had abdominal pain, and two subjects had iron deficiency anemia (IDA). Twelve subjects underwent endoscopy; one subject had duodenal ulcer, eleven subjects had antral nodular gastritis, and six subjects showed grade 2 closed type atrophic border according to the Kimura-Takemoto classification. All subjects received eradication therapy; CAM was used in five subjects with CAM susceptibility as well as in three subjects with unknown information on CAM susceptibility, and MNZ was used in five subjects with CAM resistance. Eradication was successful in twelve subjects (one unconfirmed). There were three mild adverse effects (abdominal pain or diarrhea). CONCLUSIONS Helicobacter pylori test for junior high school students represents an opportunity to diagnose the peptic ulcer, iron deficiency anemia, and gastric atrophy.

Background Proton pump inhibitors (PPI) are widely used for the treatment of gastric acid-related disease, but they are not approved for use in children in Japan. To assess the safety, pharmacokinetics, pharmacodynamics, and efficacy (gastrointestinal symptom improvement) of PPI in Japanese pediatric patients with gastric acid-related disease, we conducted an 8 week, open-label, parallel-group, multicenter, phase I/III study of once-daily oral esomeprazole use. Methods Japanese children, aged 1-14 years with gastric acid-related disease, were stratified by weight and age into five groups (10 patients/group) to receive esomeprazole as granules for suspension (10 mg) or capsules (10 mg or 20 mg) once daily. Results Esomeprazole was absorbed and eliminated rapidly in all groups, with a median time to reach maximum plasma concentration of 1.47-1.75 h, an arithmetic mean terminal elimination half-life of 0.80-1.37 h, and a weight-correlated apparent total body clearance of 0.216-0.343 L/h/kg. Area under the plasma concentration-time curve during a dosage interval and maximum plasma drug concentration were generally higher in groups given a higher dose (20 mg) or with a lower age/weight, but also in patients identified as poor metabolizers on cytochrome P450 2C19 genotype. Most patients who had any upper gastrointestinal symptoms at baseline were asymptomatic at the end of the study. Thirty-three patients (66%) reported ≥1 adverse events, including three patients who reported serious adverse events not judged to be causally related to esomeprazole. Conclusions Oral esomeprazole, at 10 mg or 20 mg once daily, had a similar safety, efficacy, and pharmacokinetic profile in Japanese pediatric patients to that previously seen in adults and Caucasian children.

We describe the cases of two childhood cancer survivors (CCS) who developed colorectal cancer at 21 and 30 years of age. They had been treated with 30 Gy abdominal irradiation and chemotherapy including platinum and high-dose alkylating agents at age 1 year, and 12 Gy total body irradiation and high-dose cyclophosphamide at age 15 years, respectively. Both had not been screened for colorectal cancer. One patient with advanced cancer died, whereas the other with early cancer was still alive at the time of writing. Two guidelines for long-term follow-up of CCS recommend that CCS who had >30 Gy irradiation receive periodic check-ups at age ≥ 35 years. The present cases suggest that CCS, even with irradiation

Human intestinal spirochetosis (HIS) is a condition in which spirochetes attach to and colonize the colorectal epithelium. To our knowledge, no comprehensive studies of HIS in young patient have been published in a developed country. This study aimed to determine the incidence and clinicopathological manifestations of HIS in Japanese patients aged less than 20 years. We retrospectively reviewed 3605 biopsy and 92 surgical specimens obtained from 479 patients admitted to Shinshu University Hospital between 1997 and 2014. All slides were reviewed independently by two pathologists to confirm the histological presence of spirochetes. Among 387 patients who underwent biopsy, the most common pathologic diagnosis was ulcerative colitis (12.6%, n = 49). Additionally, about half of the biopsy specimens showed non-specific, mildly inflamed mucosa (50.6%, n = 196); only one of these cases was HIS. On the other hand, among the surgical specimens, we found no cases of HIS. We concluded that the incidence of HIS in Japanese young patients was 0.2% (1/479 cases). The incidence of HIS in Japanese young patients was very low, and one HIS case was associated with colitis with abdominal pain.

Background The bleeding risk after cold snare polypectomy in anticoagulated patients is not known. Objective To compare the bleeding risk after cold snare polypectomy or conventional polypectomy for small colorectal polyps in anticoagulated patients. Design Prospective randomized controlled study. Setting Municipal hospital in Japan. Interventions Anticoagulated patients with colorectal polyps up to 10 mm in diameter were enrolled. Patients were randomized to polypectomy with either cold snare technique (Cold group) or conventional polypectomy (Conventional group) without discontinuation of warfarin. The primary outcome measure was delayed bleeding (ie, requiring endoscopic intervention within 2 weeks after polypectomy). Secondary outcome measures were immediate bleeding and retrieval rate of colorectal polyps. Results Seventy patients were randomized (159 polyps): Cold group (n = 35, 78 polyps) and Conventional group (n = 35; 81 polyps). The patients' demographic characteristics including international normalized ratio and the number, size, and shape of polyps removed were similar between the 2 techniques. Immediate bleeding during the procedure was more common with conventional polypectomy (23% [8/35]) compared with cold polypectomy (5.7% [2/35]) ( P = .042). No delayed bleeding occurred in the Cold group, whereas 5 patients (14%) required endoscopic hemostasis in the Conventional group ( P = .027). Complete polyp retrieval rates were identical (94% [73/78] vs 93% [75/81]). The presence of histologically demonstrated injured arteries in the submucosal layer with cold snare was significantly less than with conventional snare (22% vs 39%, P = .023). Limitation Small sample size, single-center study. Conclusions Delayed bleeding requiring hemostasis occurred significantly less commonly after cold snare polypectomy than conventional polypectomy despite continuation of anticoagulants. Cold snare polypectomy is preferred for removal of small colorectal polyps in anticoagulated patients. (Clinical trial registration number: NCT 01553565.)

Formation of an inter-diffusion phase of gadolinium-doped ceria (GDC) and yttria-stabilized zirconia (YSZ) during high-temperature sintering is a significant issue to deteriorate the electrochemical performance of solid oxide fuel cell electrodes. In the present study, microstructural change of GDC particles on a YSZ substrate and formation of a secondary phase during high-temperature sintering was observed by an in-situ transmission electron microscopy (TEM). A TEM sample was fixed on Nano-Chip (Wildfire, DENSsolutions), and the in-situ observation was carried out at 1300 °C. For comparison, an additional observation by TEM was also carried out using the sample prepared in ex-situ condition. Formation of inter-diffusion phase was observed in both experiments. However, grain growth and interfacial microstructure were different in each experiment. Based on the differences between the two tests, mechanisms of microstructural evolutions of GDC and interfacial structure are discussed.

We succeeded in fabricating 10-period coherent γ-Al2O3/Ga2O3 superlattices (SLs) on MgAl2O4 substrates by molecular beam epitaxy. By varying each layer thickness, we tuned the average Al composition (x ave) of the coherent SLs from 0.20 to 0.85, and obtained nearly-lattice-matched SLs to the substrate at x ave ~ 0.5. The lattice-matched SLs maintained coherent interfaces up to a period length of 7.2 nm in spite of a large lattice mismatch between the end members. Our results suggest lots of flexibility in designing γ-(Al x Ga1−x )2O3-based heterostructures for future functional heterojunction devices.

BACKGROUND: Endoscopic evaluation of swallowing (EES) is not commonly used by gastroenterologists to evaluate swallowing in patients with dysphagia.OBJECTIVE: To use transnasal endoscopy to identify factors predicting successful or failed swallowing of pureed foods in elderly patients with dysphagia.METHODS: EES of pureed foods was performed by a gastroenterologist using a small-calibre transnasal endoscope. Factors related to successful versus unsuccessful swallowing of pureed foods were analyzed with regard to age, comorbid diseases, swallowing activity, saliva pooling, vallecular residues, pharyngeal residues and airway penetration/aspiration. Unsuccessful swallowing was defined in patients who could not eat pureed foods at bedside during hospitalization. Logistic regression analysis was used to identify independent predictors of swallowing of pureed foods.RESULTS: During a six-year period, 458 consecutive patients (mean age 80 years [range 39 to 97 years]) were considered for the study, including 285 (62%) men. Saliva pooling, vallecular residues, pharyngeal residues and penetration/aspiration were found in 240 (52%), 73 (16%), 226 (49%) and 232 patients (51%), respectively. Overall, 247 patients (54%) failed to swallow pureed foods. Multivariate logistic regression analysis demonstrated that the presence of pharyngeal residues (OR 6.0) and saliva pooling (OR 4.6) occurred significantly more frequently in patients who failed to swallow pureed foods.CONCLUSIONS: Pharyngeal residues and saliva pooling predicted impaired swallowing of pureed foods. Transnasal EES performed by a gastroenterologist provided a unique bedside method of assessing the ability to swallow pureed foods in elderly patients with dysphagia.

Background There have been few reports on Helicobacter pylori (H. pylori) infection in asymptomatic Japanese children and adolescents. We hypothesized that the prevalence of H. pylori infection is very low among Japanese children and that clinical variables such as serum pepsinogen and iron levels are associated with H. pylori infection. Materials and Methods We conducted a cross-sectional analysis of a sample of 454 junior high school students aged 12-15 years in four areas in Nagano Prefecture. A commercial ELISA kit (E-plate Eiken H. pylori antibody) was used to measure IgG antibody against H. pylori. Serum pepsinogen and iron levels were also measured using standard methods. A urea breath test was performed for seropositive students. Results The overall prevalence of H. pylori was 3.1% (14/454). There were no significant differences in H. pylori prevalence among mountain, rural, and urban areas. The mean level of both serum pepsinogen (PG I) and PG II was significantly increased in the seropositive subjects compared with the seronegative subjects. When the cutoff values for adults (PG I: 70 ng/mL and PG I/II ratio: 3) were used, 4 of 14 subjects had PG I ≤70 ng/mL and PG I/II ratio ≤3. The results of a logistic regression analysis showed that low serum iron levels were significantly associated with H. pylori infection (P=.02). Conclusions The prevalence of H. pylori infection is as low as 3% among junior high school students aged 12-15 years in Japan. The disappearance of H. pylori is accelerating in Japanese children.

Colonoscopy is widely used to detect colorectal cancer and to remove precancerous lesions to reduce the risk of colonic cancer. To examine the benefits and limitations of cap-fitted colonoscopy compared to conventional colonoscopy in terms of technical performance and colorectal adenoma detection rate. Screening colonoscopies performed from 2009 to 2010 with or without a transparent cap were retrospectively examined to compare the rate of successful intubation, cecal intubation time, and number, size, shape, and location of adenomas detected. An inclusion criterion was visualization of >95 % of the right colon. Data from 2,301 colonoscopies (1,165 with cap-fitted colonoscopy, 1,136 without the transparent cap) were retrospectively analyzed. Procedures were performed by four experienced endoscopists. The subjects’ demographic characteristics and technical performances were similar between the two methods. The only significant difference in the technical performance between the two techniques was a shorter cecal intubation time with cap-fitted colonoscopy (5.3 vs. 6.6 min; p = 0.045) by one endoscopist. The total number of adenomas detected was significantly higher with cap-fitted colonoscopy than without the cap (586 vs. 484, respectively; p

Aim Colonoscopy may need to be rescheduledbecause of inadequate bowel preparation. We evaluatedthe effectiveness of colonoscopic enema as rescue foran inadequate 1-day bowel preparation before colonos-copy.Method Patients referred for afternoon colonoscopywere prospectively enrolled in the study during a 1-yearperiod. Patients took bowel preparation (polyethyleneglycol) solution on the morning of the endoscopy. Ifduring colonoscopy the bowel preparation was poor, anenema of polyethylene glycol solution (500 ml) wasinstilled into the colon at the level of the hepatic flexurevia the biopsy channel of the colonoscope which was thenremoved. The patient was allowed to recover from thepropofol sedation and used the bathroom to evacuatethe enema. The colonoscope was then introduced and theexamination continued.Results Of 504 patients undergoing colonoscopy, 26(4.9%) received an enema. The median age was 59(29–79) years and 19 (73%) were female. A subsequentsuccessful colonoscopy was achieved in 25 ⁄26 (96%).There were no complications. The mean time spent forthe entire colonoscopy from the initial preparation to theend of the examination including the enema was7.6 ± 1.1 h (5.4 h preparation, 0.2 h first colonos-copy + enema, 0.66 h waiting in the lavatory, 0.33 hsecond colonoscopy and 1 h for recovery).Conclusion Colonoscopic enema was highly successfulas rescue for patients with inadequate bowel preparationand avoided postponement of the procedure.Keywords Colonoscopy, bowel cleansing, enemaWhat is new in this paper?An enema given down the biopsy channel of thecolonoscope was highly successful as rescue in patientswith inadequate bowel preparation. It avoided postpone-ment of the procedure in 25 out of 26 patients whounderwent the procedure.

Aim Colonoscopy provides imperfect protection againstcolorectal cancer (CRC).In an attempt to improve cancer detection we evalu-ated the clinical features of invasive CRC detected within5 years of a negative colonoscopy.Method The details of colonoscopies performed in arural hospital in Japan were prospectively recorded at thetime of the examination. The patients were followed over5 years for the subsequent occurrence of cancer.Results In a 5-year period, 10 148 patients underwentcolonoscopy and 202 without previous colonoscopy werediagnosed with invasive CRC. Of 3212 patients with acolonoscopy negative for cancer, nine developed invasivecancer within 5 years. The ratios for invasive CRCdetected without ⁄with previous colonoscopy were 60:1in the rectum, 54:1 in the sigmoid colon, 15:1 in thedescending colon, 28:0 in the transverse colon, 31:5 inthe ascending colon and 14:1 in the caecum (P = 0.041).The ratio between left- and right-sided colonic cancer wasalso significantly different (129:3 and 45:6, P = 0.0078).Six (67%) of the invasive CRCs were in the ascendingcolon or caecum. Five of six patients with invasive CRC inthe ascending colon and caecum had right-sided smalladenomas at prior colonoscopy.Conclusion The majority of early ⁄missed CRCs wereright-sided and associated with prior right-sided colonicadenomas. Repeated colonoscopy of patients with right-sided adenomas at a shorter surveillance interval deservesconsideration.Keywords Colorectal cancer, colonoscopy, colonWhat is new in this paper?The majority of early ⁄missed colorectal cancers after anegative colonoscopy are right-sided and associated withthe presence of small adenomas in the area of the priorcolonoscopy. Improved methods for detecting small orflat lesions in the right-sided colon may reduce invasivecolorectal cancer after negative colonoscopy. The surveil-lance interval for those with right-sided adenomas shouldbe reconsidered.