Clinical Guidelines for Diagnosis and Management of Peutz-Jeghers Syndrome in Children and Adults.

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.

Serum positivity of serum anti-tissue transglutaminase immunoglobulin A antibodies in Japanese children with inflammatory bowel disease.

BACKGROUND: Serum anti-tissue transglutaminase immunoglobulin A antibody (tTG-IgA) is a screening test for celiac disease (CeD). In recent years, there have several reports of combined inflammatory bowel disease (IBD) and CeD in children. The purposes of this study are to research the positivity of the tTG-IgA antibody in Japanese children, and whether IBD and CeD co-occur. METHODS: We examined tTG-IgA as a screening test for CeD in symptomatic pediatric patients with IBD (cases) and those without IBD (controls, non-IBD). Those with tTG-IgA levels of 10 U/mL or higher were considered positive. All patients had routine biopsy specimens taken from the second part and bulbus of the duodenum, and were evaluated histologically based on the Marsh classification. RESULTS: Thirty-one patients in the IBD group and 53 patients in the non-IBD group were included. The tTG-IgA was positive in five cases (5.9%) and median titer of positive cases was 12.3 U/mL (10.2-41.7). One patient in the IBD group (3.2%) and four patients in the non-IBD group (7.8%) were positive for tTG-IgA. No cases showed histological features of CeD. There were no statistically significant differences in age, sex, symptoms and laboratory tests between the tTG-IgA positive and negative groups. Patients among the IBD and the non-IBD groups that were tTG-IgA positive demonstrated symptoms after wheat consumption. CONCLUSIONS: We identified a patient who was positive for tTG-IgA antibodies who experienced abdominal symptoms due to wheat ingestion, indicative of subclinical CeD. Further investigation is needed to clarify the co-occurrence of IBD and CeD among Japanese children.

Small bowel endoscopy for children: Collaboration of capsule endoscopy and device-assisted enteroscopy.

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.

Elemental diet therapy for eosinophilic gastroenteritis and dietary habits.

BACKGROUND: 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 analyzed retrospectively the medical records of four 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: Elemental diet therapy 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.

Clinical practice guidelines for the management of children with mother-to-child transmitted hepatitis C virus infection.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The guidelines will be helpful in the management of children with hepatitis C MTC transmission.

Safety and efficacy of the endoscopic delivery of capsule endoscopes in adult and pediatric patients: Multicenter Japanese study (AdvanCE-J study).

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 <16 years and ≥16 years, respectively (P = 0.6661), but the total enteroscopy rate was higher in the first group (91.7%) than in the second (76.2%, P < 0.0001), for whom impossible ingestion (87.3%) was significantly more common than prolonged lodging in the stomach (64.2%, P = 0.0010). Successful PC and CCE delivery to the duodenum occurred in 84.1% and 28.6%, thereafter the patency confirmation rate and total colonoscopy rate was 100% and 61.5%, respectively. The height, weight, and age cutoff points in predicting spontaneous ingestion were 132 cm, 24.8 kg, and 9 years 2 months, respectively, in patients aged <16 years. Patients aged ≥16 years could not swallow the SBCEs mainly due to dysphagia (75.0%); those who retained it in the esophagus due to cardiac disease (28.6%), etc. and in the stomach due to diabetes mellitus (15.7%), etc. CONCLUSIONS: This large-scale study supports the safety and efficacy of ED in adult and pediatric patients. UMIN000042020.

Clinicopathological features of nodular gastritis in three classes of age.

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 < .001) and young (p < .001) groups. Similar results were seen for neutrophil infiltration scores in the gastric body. To clarify the characteristics of older nodular gastritis, we investigated 1056 older patients (66 with nodular gastritis, 754 with atrophic gastritis, and 236 H. pylori-negative). The scores for mononuclear and neutrophil cell infiltration in the gastric body were significantly higher in nodular gastritis patients than in atrophic gastritis patients (both p < .001) and patients negative for H. pylori (both p < .001). CONCLUSIONS: The inflammatory changes in the gastric body in older nodular gastritis patients were more severe as compared with those in pediatric and young nodular gastritis patients in addition to older atrophic gastritis patients.

Nationwide survey of pediatric gastrointestinal endoscopy in Japan.

BACKGROUND AND AIM: The implementation rates of pediatric gastrointestinal endoscopy are increasing with advancements in the devices used and pediatricians' skills. As part of the Japan Pediatric Endoscopy Study Group, we aimed to investigate the rates of pediatric gastrointestinal endoscopy use and the associated adverse events through a nationwide survey. METHODS: A questionnaire was sent to 630 institutions in Japan. The numbers of pediatric gastrointestinal endoscopy cases and adverse events occurring during endoscopy, from April 2011 to March 2016, were investigated. RESULTS: Responses were obtained from 445 facilities. The total number of pediatric gastrointestinal endoscopies was 37 447 and that of endoscopic examinations was 32 219 (86.0%), with esophagogastroduodenoscopy accounting for 18 484 cases; ileal colonoscopy, 11 936; endoscopic retrograde cholangiopancreatography, 389; wireless capsule endoscopy, 897; and balloon-assisted enteroscopy, 513. The number of endoscopic treatments was 5228, followed by balloon dilatation (1703), foreign body removal (989), and polypectomy (822); 201 adverse events (0.54%) occurred, 79 of which presented during endoscopic examination (0.25%). Eight serious perforations were noted in 0.0054% and 0.025% of those undergoing esophagogastroduodenoscopy and colonoscopy, respectively. Overall, 122 adverse events (2.33%) occurred in association with endoscopic treatment. One case of cardiopulmonary arrest occurred because of accidental extubation. However, no deaths occurred. CONCLUSION: Endoscopic examinations had a slightly higher adverse event rate, because of an increase in endoscopic retrograde cholangiopancreatography and small intestine enteroscopy, than that reported in previous studies, but the adverse event rate of endoscopic treatment did not increase.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2020 for the Clinical Practice of Hereditary Colorectal Cancer.

Hereditary colorectal cancer (HCRC) accounts for < 5% of all colorectal cancer cases. Some of the unique characteristics commonly encountered in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics necessitate different management approaches, including diagnosis, treatment or surveillance, from sporadic colorectal cancer management. There are two representative HCRC, named familial adenomatous polyposis and Lynch syndrome. Other than these two HCRC syndromes, related disorders have also been reported. Several guidelines for hereditary disorders have already been published worldwide. In Japan, the first guideline for HCRC was prepared by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), published in 2012 and revised in 2016. This revised version of the guideline was immediately translated into English and published in 2017. Since then, several new findings and novel disease concepts related to HCRC have been discovered. The currently diagnosed HCRC rate in daily clinical practice is relatively low; however, this is predicted to increase in the era of cancer genomic medicine, with the advancement of cancer multi-gene panel testing or whole genome testing, among others. Under these circumstances, the JSCCR guidelines 2020 for HCRC were prepared by consensus among members of the JSCCR HCRC Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR guidelines 2020 for HCRC.

Comprehensive Targeted Sequencing Identifies Monogenic Disorders in Patients With Early-onset Refractory Diarrhea.

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.

Trends in gastroesophageal reflux disease in Japanese children and adolescents.

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.

The updated JSPGHAN guidelines for the management of Helicobacter pylori infection in childhood.

The Japan Pediatric Helicobacter pylori Study Group published the first guidelines on childhood H. pylori infection in 1997. They were later revised by the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition (JSPGHAN). The H. pylori eradication rates, when employing triple therapy with amoxicillin and clarithromycin, currently recommended as the first-line therapy of H. pylori infection in Japan, have substantially decreased, creating an important clinical problem worldwide. In Japanese adults, the "test-and-treat" strategy for H. pylori infection is under consideration as an approach for gastric cancer prevention. However, the combined North American and European pediatric guidelines have rejected such a strategy for asymptomatic children. As risk for gastric cancer development is high in Japan, determining whether the "test-and-treat" strategy can be recommended in children has become an urgent matter. Accordingly, the JSPGHAN has produced a second revision of the H. pylori guidelines, which includes discussion about the issues mentioned above. They consist of 19 clinical questions and 34 statements. An H. pylori culture from gastric biopsies is recommended, not only as a diagnostic test for active infection but for antimicrobial susceptibility testing to optimize eradication therapy. Based upon antimicrobial susceptibility testing of H. pylori strains (especially involving clarithromycin), an eradication regimen including use of the antibiotics to which H. pylori is susceptible is recommended as the first-line therapy against H. pylori-associated diseases. The guidelines recommend against a "test-and-treat" strategy for H. pylori infection for asymptomatic children to protect against the development of gastric cancer because there has been no evidence supporting this strategy.

Clinical features of Helicobacter pylori antibody-positive junior high school students in Nagano Prefecture, Japan.

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.

Clinical Safety and Utility of Pediatric Balloon-assisted Enteroscopy: A Multicenter Prospective Study in Japan.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: This prospective multicenter observational study documents the efficacy of BAE in pediatric patients.

Oral esomeprazole in Japanese pediatric patients with gastric acid-related disease: Safety, efficacy, and pharmacokinetics.

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.

Targeted Sequencing and Immunological Analysis Reveal the Involvement of Primary Immunodeficiency Genes in Pediatric IBD: a Japanese Multicenter Study.

PURPOSE: 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. METHODS: In total, 35 Japanese patients <16 years of age suffering from IBD, including 27 patients aged <6 years with very early-onset IBD, were enrolled in this multicenter study. Exome and targeted gene panel sequencing was performed for all patients. Mutations in genes responsible for primary immunodeficiency diseases (PID) and clinical and immunological parameters were evaluated according to disease type. RESULTS: We identified monogenic mutations in 5 of the 35 patients (14.3 %). We identified compound heterozygous and homozygous splice-site mutations in interleukin-10 receptor A (IL-10RA) in two patients, nonsense mutations in X-linked inhibitor of apoptosis protein (XIAP) in two patients, and a missense mutation in cytochrome b beta chain in one patient. Using assays for protein expression levels, IL-10 signaling, and cytokine production, we confirmed that the mutations resulted in loss of function. For each patient, genotype was significantly associated with clinical findings. We successfully treated a patient with a XIAP mutation by allogeneic cord blood hematopoietic stem cell transplantation, and his symptoms were ameliorated completely. CONCLUSIONS: Targeted sequencing and immunological analysis are useful for screening monogenic disorders and selecting curative therapies in pediatric patients with IBD. The genes responsible for PID are frequently involved in pediatric IBD and play critical roles in normal immune homeostasis in the gastrointestinal tract.

Helicobacter pylori infection and its related factors in junior high school students in Nagano Prefecture, Japan.

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.

Human intestinal spirochetosis in Japanese patients aged less than 20 years: Histological analysis of colorectal biopsy and surgical specimens obtained from 479 patients.

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.

Endoscopic findings of esophagogastric junction in children.

Esophagogastric landmarks are recognizable in the same way both in children and in adults, and palisade-shaped vessels can be observed at the distal position of esophageal mucosa, even in infants. Few studies have been done in respect to Barrett's esophagus (BE) in children. Incidence of endoscopically suspected BE among all children undergoing esophagogastroduodenoscopy (EGD) is approximately 0.25-1.4%, but can be up to 9.7% in patients with gastroesophageal reflux disease (GERD). Some data suggest that BE is an acquired disorder and point to the possibility of a congenital component in combination with severe mucosal injury. Recent reports noted that multilayered epithelium (ME), which shows morphological and immunocytochemical characteristics of both squamous and columnar epithelium, is associated with goblet cell metaplasia in adult patients with columnar-lined esophagus. The role of ME in the development of intestinal metaplasia in children is uncertain. Furthermore, detailed mechanisms about how short-segment BE (SSBE) changes to long-segment BE (LSBE) are not yet well understood. Further studies are required to understand the pathological esophagogastric junction (EGJ) and BE in children based on reliable epidemiological data and analysis especially in children who have reflux symptoms. Better understanding of the pediatric EGJ and BE may allow improved diagnosis, monitoring, therapy and, therefore, prognosis of GERD-related disorders in adulthood.

Endoscopic gastric mucosal atrophy distinguishes the characteristics of superficial esophagogastric junction adenocarcinoma.

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 < 0.0001); and had higher rates of gastroesophageal reflux disease symptoms (43% vs 12%, P = 0.017), mucosal breaks (25% vs 15%, P = 0.009), Barrett's esophagus (BE, 78% vs 42%, P < 0.0001), and tumors above the EGJ (81% vs 19%, P < 0.0001) and on the upper-right side (74% vs 38%, P < 0.0001) than the former group. Multivariate analysis showed that H. pylori positivity (odds ratio [OR] = 13.0, P < 0.001), long-segment BE (OR = 0.025, P = 0.033), and longitudinal (OR = 8.6, P = 0.001) and circumferential (OR = 4.7, P = 0.006) tumor locations were independently associated with gastric mucosal atrophy. CONCLUSION: Two distinct types of EGJ cancer were identified, with and without endoscopic gastric mucosal atrophy. These types were associated with different tumor locations.