departmental bulletin paper

Background: Deterioration of swallowing function markedly impairs quality of life, a problem particularly significant in Japanʼs rapidly aging population. Dysphagia management remains challenging due to limited clinical resources and lack of an organized support system. Objective: To illustrate the effectiveness of multidisciplinary collaboration in facilitating the transition from home parenteral nutrition (HPN) to complete oral intake. Case Presentation: A 66-year-old woman with severe dysphagia secondary to submandibular gland inflammation and prolonged impaired consciousness was maintained on total parenteral nutrition (TPN) during hospitalization because oral intake was deemed impossible. After discharge on HPN, a multidisciplinary home-care team─comprising physicians, nurses, registered dietitians, and certified dysphagia nurses─ initiated structured dietary and swallowing interventions. The patient restored full oral feeding within one year through structured assessment and staged texture advancement. Results: Swallowing ability improved from Repetitive Saliva Swallowing Test (RSST) 0, Modified Water Swallowing Test (MWST) 0 and Kuchikara Taberu Balance Chart (KTBC) 22 to RSST 3, MWST 4 and KTBC 53. Oral intake reached 1200 kcal/day, allowing discontinuation of HPN. Conclusion: Coordinated multidisciplinary collaboration with continuous information sharing between care settings enabled safe restoration of oral intake in a patient previously judged unable to eat orally. Regular reassessment of swallowing function is crucial to identify patients with recovery potential.

Transient receptor potential vanilloid 4 (TRPV4) channels, expressed in presynaptic membranes and astrocytes, have attracted attention as factors involved in epilepsy. We investigated the role of TRPV4 channels as therapeutic targets for epilepsy. We injected Penicillin G (PG) into the cortex of wild-type (WT) mice or TRPV4 KO mice. We also injected RN 1734, a TRPV4 antagonist, before and after PG injection. We recorded epileptic discharges (EDs) and the concentration of extracellular glutamate in the mice. In WT mice, the glutamate concentration increased after PG injection and EDs occurred. In TRPV4 KO mice, the glutamate concentration and beta-band power of the EDs were lower than that in WT mice. When WT mice were administered RN 1734 prior to PG injection, both the glutamate concentration and spike amplitude at late phase following PG injection were comparable to those in TRPV4 KO mice. However, when RN 1734 was administered after the onset of EDs, the alleviation of EDs lasted for only 10 min, and the glutamate concentration did not decrease. RN 1734 modulated EDs in a timing-dependent manner, with significant effects during ongoing EDs and limited effects following pre-treatment. These results indicate that TRPV4 antagonists modulate glutamate dynamics in an activity-dependent manner.

Background: Eosinophilic chronic rhinosinusitis (ECRS) is generally characterized by refractory type 2 inflammation along with severe asthma. Although tezepelumab, an anti-thymic stromal lymphopoietin (TSLP) monoclonal antibody, has broad efficacy in severe asthma, its effects on sinonasal inflammation in ECRS remain unclear. In this retrospective observational study, we investigated the radiological and clinical changes in patients with ECRS and severe asthma treated with tezepelumab. Methods: Clinical data, blood eosinophil counts, fractional exhaled nitric oxide (FeNO), total serum IgE levels, lung function, and paranasal sinus CT findings of seven patients with ECRS who received tezepelumab for comorbid severe asthma at a single tertiary care center between 2022 and 2024, were collected. Radiologic severity was assessed using the Lund-Mackay score (LMS) at baseline and ≥6 months after treatment initiation. Results: The median LMS showed a trend toward reduction from baseline to ≥6 months, although this difference did not reach statistical significance (p = 0.051). In contrast, blood eosinophil counts, serum IgE levels, FeNO levels, and the FEV_1/FVC ratio did not show statistically significant changes during the observation period. Conclusion: Tezepelumab therapy showed a trend toward reduction in the Lund-Mackay score in patients with ECRS and severe asthma, although statistical significance was not reached. Systemic biomarkers and lung function remained stable.

Surgical resection is the most effective treatment for gastrointestinal cancer; however, a novel treatment is needed for unresectable cases. We have developed an immunotherapy for gastrointestinal cancers. In 1990, we devised a combination immunotherapy for hepatocellular carcinoma using interleukin-2, OK-432, Adriamycin, cyclophosphamide, and famotidine, which resulted in complete response in 4 out of 24 patients. Subsequently, we developed immune cell therapies for gastrointestinal cancers. Tumor antigen-specific immunity was first reported in 1991. We administered cancer vaccines using epitope peptides derived from oncoantigens for colorectal and pancreatic cancers. As a result, antigen-specific immunity was induced at a high frequency, and cases showing long-term antitumor effects were observed, whereas cases that were ineffective were also observed; therefore, we searched for the cause. A comprehensive analysis of lymphocytes, serum, and tumor tissues revealed the presence of many immunosuppressive factors. Therefore, we developed an immune adjuvant that induces cytotoxic T lymphocytes without fatigue markers and tumor antigen-specific peptides. This vaccine was administered preoperatively in 20 cases of hepatocellular carcinoma; 12 cases showed significant lymphocyte invasion into tumors and tumor necrosis in 6 cases, and these results suggested that hepatocellular carcinoma changed into a hot tumor. This immunotherapy is expected to be useful in combination with checkpoint inhibitors.

The fecal immunochemical test for hemoglobin (FIT) is widely used for colorectal cancer screening but shows limited sensitivity for detecting advanced colorectal adenomas. To overcome this limitation, we evaluated a combined approach using FIT and fecal DNA testing for methylated somatostatin (SST). Fecal samples were collected from healthy subjects, patients with non-advanced adenoma, advanced adenoma, and colorectal cancer. SST methylation levels were quantified using droplet digital PCR after treatment with methylation-sensitive restriction enzymes. Using logistic multivariate analysis, we developed the FAMS (FIT, age, methylated SST) index. The FAMS index improved sensitivity for detecting advanced adenoma compared with FIT alone while maintaining high specificity. Even at higher specificity, the sensitivity of the FAMS index remained higher than that of FIT. These results suggest that the FAMS index can non-invasively enhance early detection of advanced colorectal adenoma and may serve as a promising tool for screening.