Multiple endocrine neoplasia type 2B diagnosed after small intestinal volvulus with progressive megacolon in an adolescent.

Multiple endocrine neoplasia type 2B is a rare autosomal dominant disease characterized by the presence of medullary thyroid carcinoma, pheochromocytoma, Marfan-like fatigue, a peculiar face with thickening of the lips, mucosal neuromas on the lips and tongue, and gastrointestinal phenomena. Most patients harbor pathological variants of the RET gene. Herein, we present the first case of a 14 year-old boy who experienced small intestinal volvulus along with a megacolon, and he was diagnosed with multiple endocrine neoplasia type 2B. The patient complained of constipation since he was 2 years old and slowly progressive abdominal distension at school age. At 14 years of age, he presented with remarkable megacolon mimicking Hirschsprung's disease and complicated with small intestinal volvulus. The volvulus was successfully repaired, and the particularly dilated transverse colon was resected following a rectal biopsy. Histopathological evaluation of the resected transverse colon revealed to be compatible with ganglioneuromatosis. After emergency surgery, the patient was diagnosed with multiple endocrine neoplasia type 2B with medullary thyroid carcinoma, and a de novo variant of RET was confirmed. Gastroenterologists should consider it when treating patients with constipation, especially those with megacolon. Therefore, timely diagnosis may lead to appropriate treatment of medullary thyroid carcinoma and improve mortality.

Safety and efficacy of vedolizumab in pediatric patients with ulcerative colitis: multicenter study in Japan.

BACKGROUND: Vedolizumab (VDZ) is a humanized monoclonal antibody that binds to α4ß7 integrin expressed in T-lymphocytes and is gut selective. Few studies have evaluated the safety and efficacy of VDZ in pediatric ulcerative colitis (UC) patients, especially from Asia. METHODS: A longitudinal multicenter retrospective study was conducted at 10 Japanese tertiary medical institutions. Patients aged ≤18 years old who received VDZ for UC between January 2019 and July 2021 were enrolled. Information on the clinical characteristics, prior/concomitant treatment, and safety during the observation period was collected. RESULTS: The data obtained from 48 patients (males, n = 30; females, n = 18) were analyzed. The median age at VDZ induction was 14 (range 4-18) years old. VDZ was indicated in 73% of patients as switching from previous biologics due to primary failure, loss of response, and adverse events (AEs) and was the first biologic in 27%. Remission was achieved or maintained at weeks 14, 30, and 54 in 79.2%, 75.0%, and 65.8% of patients, respectively. There were no significant differences between the number of previous biologics exposures and VDZ effectiveness. The hematocrit, serum albumin concentrations, and erythrocyte sedimentation rate (ESR) at baseline differed significantly by VDZ effectiveness. Nine AEs, including infusion reaction, were noted in seven (14.3%) patients. There were no severe AEs related to VDZ administration. CONCLUSIONS: VDZ was safe and effective in children with UC. The hematocrit, albumin, and ESR at VDZ initiation might be predictors for VDZ effectiveness. VDZ may be an important option for pediatric patients and can be used as an alternative to immunomodulators.

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.

Number and distribution of eosinophils and lymphocytes in the Japanese pediatric gastrointestinal tract: in search of a definition for "abnormally increased eosinophils".

BACKGROUND: 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. METHODS: We examined 131 biopsy cases without significant clinical history, endoscopic abnormality, or histological abnormality. Immunohistochemical analysis of CD3 and CD20 was performed. RESULTS: 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. CONCLUSIONS: 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.

Extremely young case of small bowel intussusception due to Peutz-Jeghers syndrome with nonsense mutation of STK11.

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.

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.

Concentrations of various forms of vitamin B6 in ginkgo seed poisoning.

A 2-year-old girl required medical attention for a sudden onset of repetitive tonic-clonic convulsions after ingesting 20-30 ginkgo seeds. Concentrations of the major forms of circulating vitamin B6, pyridoxal-5'-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid, as well as the known ginkgo seed toxin 4'-O-methylpyridoxine (MPN) were measured in the serum and cerebrospinal fluid (CSF). PLP is an active form of vitamin B6 and necessary for γ-aminobutyric acid (GABA) production. High MPN concentrations were observed in both the serum and CSF. As the PLP to PL ratio was markedly decreased in serum and CSF examinations, we suspected the ratio to be important in GABA production. This case report provides novel information on the metabolism of vitamin B6 in humans as a result of ginkgo seed poisoning.