廣岡 芳樹

The new Kyoto guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) provide evidence-based recommendations for the diagnosis and treatment of IPMN. Endoscopic ultrasonography (EUS) is a diagnostic modality with a high spatial resolution that allows detailed observation and obtaining cyst fluid or tissue samples via EUS-guided fine needle aspiration (EUS-FNA). Currently, EUS is an indispensable examination method for the diagnosis of pancreatic diseases. On the other hand, there have been concerns that EUS imaging tends to be highly operator-dependent, and may lack objectivity. Previous guidelines have assigned EUS as an option for patients with worrisome features. However, recent reports indicate that the sensitivity of EUS for the diagnosis of mural nodules (MNs) is more than 90%, comparable or superior to that of contrast-enhanced computed tomography or magnetic resonance cholangiopancreatography. The specific advantages of EUS in the diagnosis of IPMN are: (1) high spatial resolution imaging for the diagnosis of MNs, (2) contrast-enhanced EUS for differentiation of intra-cystic MNs from mucous clots, and (3) pathological diagnosis using EUS-FNA and differential diagnosis of a pancreatic cystic tumor by cystic fluid analysis. In order to utilize EUS in the diagnosis of IPMN, endoscopists are required to have the skills to provide sufficiently objective imaging findings.

PURPOSE: This study aimed to clarify the current treatment status for biliary tract cancers based on data from the National Clinical Database (NCD) in Japan. METHODS: Total 3895 cases of biliary tract cancers registered in the NCD during 2021 were included. We identified the rates of resection, R0 resection, postoperative complications, and incidences of lymph node metastasis for gallbladder carcinoma, perihilar cholangiocarcinoma, distal bile duct carcinoma, and ampullary carcinoma. RESULTS: The number of biliary tract cancers registered in the NCD during 2021 was 3895 (1775 in extrahepatic bile duct carcinoma, 1422 in gallbladder carcinoma, and 698 in ampullary carcinoma). In gallbladder carcinoma, the resection (89.59%) and R0 resection rates (87.99%) were favorable, and the complication rate (6.05%) was lower than that of others. However, the postoperative complication rate could be higher in T3-T4 cases and when extrahepatic bile duct resection was performed concomitantly. Lymph node metastasis was frequently seen in 12.60% at the No. 13a lymph node. In perihilar cholangiocarcinoma, the R0 resection (69.82%) and complication rates (16.75%) were significantly lower and higher, respectively. In distal cholangiocarcinoma and ampullary carcinoma, metastasis was observed in approximately 2% and 10% of the dissected No. 16b1 para-aortic lymph nodes, respectively. In conclusion, although short-term surgical outcomes for biliary tract cancers in Japan might be acceptable, the significantly lower R0 resection and higher complication rates of perihilar cholangiocarcinomas indicate additional challenges for surgeons in the future and should continue to be monitored by the Japanese Society of Hepatobiliary and Pancreatic Surgery.

Feline atopic skin syndrome (FASS) is a chronic inflammatory skin disease characterized by itching and dermatitis. While the relationship between the gut microbiota and atopic dermatitis (AD) has been highlighted, exploring gut-targeted therapies for FASS remain limited. This study aimed to evaluate the effects of a parasynbiotic containing 1-kestose and heat-killed Lactobacillus plantarum FM8 on clinical symptoms and gut microbiota in cats with FASS. Eleven FASS cats were treated with a parasynbiotic containing 1-kestose (400 mg/day) and heat-killed FM8 (2.0 × 1010 CFU/day) for 8 weeks. Clinical symptoms were assessed using the SCORing Feline Allergic Dermatitis (SCORFAD), investigator pruritus score (IPS), and rating of global assessment of improvement (GAI). Fecal microbiota composition was analyzed through 16S rRNA sequencing, with 16 healthy cats serving as controls. Parasynbiotic intervention significantly reduced SCORFAD and IPS scores. GAI scores improved in 10 of 11 cats, with the most severe case maintaining a score of 3. The β-diversity analysis showed no significant differences; however, a trend toward variation was observed between the healthy control cats and the baseline group of FASS cats, as well as between the healthy control cats and post- intervention groups. The abundance of Collinsella stercoris was significantly higher in FASS cats than in healthy controls, and it significantly decreased after parasynbiotic intervention, suggesting potential improvements in gut health and inflammation. This study is the first to demonstrate the potential benefits of parasynbiotic administration in FASS, showing improvements in clinical symptoms and partial modulation of the gut microbiota. These findings highlight parasynbiotic administration as a compelling therapeutic approach for FASS, offering new possibilities for innovative interventions aimed at the gut–skin axis.

Recent studies have linked Ruminococcus gnavus to inflammatory bowel disease and Fusobacterium nucleatum to various cancers. Agarooligosaccharides (AOS), derived from the acid hydrolysis of agar, have shown significant inhibitory effects on the growth of R. gnavus and F. nucleatum at concentrations of 0.1 and 0.2%, respectively. RNA sequencing and quantitative reverse-transcription PCR analyses revealed the downregulation of fatty acid biosynthesis genes (fab genes) in these bacteria when exposed to 0.1% AOS. Furthermore, AOS treatment altered the fatty acid composition of R. gnavus cell membranes, increasing medium-chain saturated fatty acids (C8, C10) and C18 fatty acids while reducing long-chain fatty acids (C14, C16). In contrast, no significant growth inhibition was observed in several strains of Bifidobacteria and Lactobacillales at AOS concentrations of 0.2 and 2%, respectively. Co-culture experiments with R. gnavus and Bifidobacterium longum in 0.2% AOS resulted in B. longum dominating the population, constituting over 96% post-incubation. In vivo studies using mice demonstrated a significant reduction in the Lachnospiraceae family, to which R. gnavus belongs, following AOS administration. Quantitative PCR also showed lower levels of the nan gene, potentially associated with immune disorders, in the AOS group. These findings suggest that AOS may introduce a novel concept in prebiotics by selectively inhibiting potentially pathogenic bacteria while preserving beneficial bacteria such as Bifidobacteria and Lactobacillales.

Aim: This study aimed to establish a non-invasive, rapid, and cost-effective method to assess the potential risk of immune and psychiatric disorders by quantifying nan gene levels in gut microbiota, specifically focusing on Ruminococcus gnavus and other Lachnospiraceae species associated with mucin degradation. Methodology: We first designed a primer set targeting the consensus sequence of the nanA gene, which is highly conserved within nan gene clusters. To validate this primer set, we performed Next-Generation Sequencing (NGS) on the PCR-amplified fragments. To explore the association between nan levels and immune or psychiatric disorders, we conducted qPCR to quantify nan levels in the intestines, analyzing intestinal DNA from both allergy-induced mice with or without fructan treatment, and dogs with or without aggressive behavior. Additionally, to assess whether nan levels reflect the clinical status of immune disorders, fecal samples were collected from 45 patients with ulcerative colitis (UC) and analyzed for nan levels. Results: NGS analysis of DNA fragments amplified from various intestinal samples using the nan primer set confirmed the presence of nanA sequences from R. gnavus and other members of the Lachnospiraceae family, including Blautia and Dorea species. The qPCR quantification of nan levels using this primer set revealed that allergy-induced mice treated with fructans, which are known to be associated with lower allergy scores compared to untreated mice, exhibited significantly reduced nan levels. Additionally, the nan levels of aggressive dogs were substantially higher than those of non-aggressive dogs. Notably, nan levels were also substantially elevated in patients with UC in comparison to the healthy control individuals. Conclusion: qPCR-based measurement of nan levels in gut microbiota shows potential for selectively detecting pathogenic nan-harboring strains and may reflect the clinical status of immune and psychiatric disorders. This approach could provide a non-invasive, rapid, and cost-effective method for assessing the risk of these disorders.