Capsule endoscopy for small‐intestinal disorders: Current status

Small‐bowel capsule endoscopy (SBCE) is used widely because of its non‐invasive and patient‐friendly nature. SBCE can visualize entire small‐intestinal mucosa and facilitate detection of small‐intestinal abnormalities. In this review article, we focus on the current status of SBCE. Several platforms for SBCE are available worldwide. Third‐generation SBCE (PillCam^® SB3) has a high‐resolution camera equipped with an adaptive frame rate system. Several software modes have been developed to reduce the reading time for capsule endoscopy and to minimize the possibility of missing lesions. The main complication of SBCE is capsule retention. Thus, the main contraindication for SBCE is known or suspected gastrointestinal obstruction unless intestinal patency is proven. Possible indications for SBCE are obscure gastrointestinal bleeding, Crohn's disease, small‐intestinal polyps and tumors, and celiac disease. Colon capsule endoscopy (CCE) can observe inflamed colonic mucosa non‐invasively, and allows for the continuous and non‐invasive observation of the entire intestinal tract (pan‐endoscopy). Recently, application of CCE as pan‐enteric endoscopy for inflammatory bowel diseases (including Crohn's disease) has been reported. In the near future, reading for CE will be assisted by artificial intelligence, and reading CE videos for long periods will not be required.     

Non-clinical pharmacokinetic profiles of rovatirelin,an orally available thyrotropin-releasing hormone analogue

1. The non-clinical pharmacokinetic profiles of rovatirelin, a novel thyrotropin-releasing hormone (TRH) analogue, were investigated in vivo and in vitro.

2. Rovatirelin orally administered to rats and dogs was rapidly absorbed and bioavailability was estimated to be 7.3 and 41.3%, respectively. The extent of plasma protein binding of rovatirelin in rats, dogs, and humans was low in all species (～15%). The permeability of rovatirelin from blood to brain (permeability-surface area) ranged from 1.04?±?0.14 to 1.29?±?0.28?μL/min/g in rats, and rovatirelin was stable in rat plasma and brain homogenates.

3. The metabolite pattern was qualitatively similar in vitro and in vivo. In animals, rovatirelin aminopentanoic acid (rovatirelin-acid), rovatirelin aminopentanone (rovatirelin-ketone), rovatirelin pyrrolidine (4S)-hydroxy (rovatirelin-OH), (thiazoylalanyl)methylpyrrolidine (TAMP), 3-(4-thiazoyl)-l-alanine (TA), and unknown metabolites were observed. In human hepatocytes, TAMP was mainly formed and no unique human metabolite was observed.

4. The radioactivity from administered [¹⁴C]rovatirelin was predominantly excreted in faeces in rats and dogs, and almost all radioactivity was recovered 168?h after administration. Absorption, brain penetration, and stability of rovatirelin in the brain were greater than for taltirelin.

5. Thus, orally administered rovatirelin is a potentially improved treatment for spinocerebellar degeneration compared with taltirelin.     

Japanese version of The Cancer Genome Atlas,JCGA, established using fresh frozen tumors obtained from 5143 cancer patients

This study aimed to establish the Japanese Cancer Genome Atlas (JCGA) using data from fresh frozen tumor tissues obtained from 5143 Japanese cancer patients, including those with colorectal cancer (31.6%), lung cancer (16.5%), gastric cancer (10.8%) and other cancers (41.1%). The results are part of a single‐center study called “High‐tech Omics‐based Patient Evaluation” or “Project HOPE” conducted at the Shizuoka Cancer Center, Japan. All DNA samples and most RNA samples were analyzed using whole‐exome sequencing, cancer gene panel sequencing, fusion gene panel sequencing and microarray gene expression profiling, and the results were annotated using an analysis pipeline termed “Shizuoka Multi‐omics Analysis Protocol” developed in‐house. Somatic driver alterations were identified in 72.2% of samples in 362 genes (average, 2.3 driver events per sample). Actionable information on drugs that is applicable in the current clinical setting was associated with 11.3% of samples. When including those drugs that are used for investigative purposes, actionable information was assigned to 55.0% of samples. Germline analysis revealed pathogenic mutations in hereditary cancer genes in 9.2% of samples, among which 12.2% were confirmed as pathogenic mutations by confirmatory test. Pathogenic mutations associated with non–cancerous hereditary diseases were detected in 0.4% of samples. Tumor mutation burden (TMB) analysis revealed 5.4% of samples as having the hypermutator phenotype (TMB ≥ 20). Clonal hematopoiesis was observed in 8.4% of samples. Thus, the JCGA dataset and the analytical procedures constitute a fundamental resource for genomic medicine for Japanese cancer patients.     

Oral plexiform schwannoma with unusual epithelial induction

Rare epithelial structures in benign nerve sheath tumors are almost always glandular in appearance. We describe a case of intraoral plexiform schwannoma with concurrent squamous epithelial hyperplasia. The lesion occurred as a pigmented nodule on the gingiva of a 35‐year‐old woman with no systemic involvement. Histologically, unencapsulated, plexiform fascicular proliferations of schwann cells could be traced from the submucosa to the lamina propria, finally making direct contact with heavily pigmented, elongated rete ridges of the overlying epithelium. Also noted was a schwannian network centered on clustered odontogenic epithelial rests of mature squamous‐type, the number and size of which had markedly increased. Impressive immunoprofiles of periepithelial neural microfascicles included the complete absence of axon and perineurium and the unexpected presence of endoneurial fibroblasts. The repertoire of epithelial changes was in a confined area with no extension beyond, supporting hyperplasia induction by an underlying/surrounding schwannoma.     

Clinical features of 22q11.2 deletion syndrome related to hearing and communication

Abstract

Background: Individuals with 22q11.2 deletion syndrome (22q11.2DS) exhibit various phenotypes.

Objective: To compare the clinical and otorhinolaryngological features of Japanese patients with 22q11.2DS with those of patients reported in Western literature.

Materials and methods: We retrospectively assessed the medical records of 17 Japanese patients with 22q11.2DS and compared our findings with previously reported findings in Western literature.

Results: Hearing loss was the most frequent complaint (n?=?8, 47%), followed by articulation disorders and/or nasopharyngeal closure failure (n?=?4, 24%) and language development delay (n?=?2, 12%). Ten patients (59%) had hearing loss regardless of the chief complaint (total 15 ears – mild, 9; moderate, 6). Four patients had bilateral hearing loss. One patient (6%) underwent tympanostomy tube placement for refractory exudative otitis media, another (6%) underwent myringoplasty, and three patients (18%) underwent tympanoplasties for chronic otitis media or middle ear malformation. Previous studies in Western countries reported similar results in terms of frequency of hearing loss, severity of hearing loss, and the percentage of middle ear malformations.

Conclusions: The otorhinolaryngological characteristics of Japanese patients with 22q11.2DS were similar to those in Western countries. Hearing loss was primarily caused by disorders like otitis media and middle ear malformation.

Significance: Our findings may aid treatment planning for Asian patients with 22q11.2DS.