Keio University Hospital

The aim of this review was to clarify the differences in therapeutic intent and indications for salvage surgery following treatment with epidermal growth factor receptor tyrosine kinase inhibitor versus definitive chemoradiotherapy. Unresolved issues in molecular targeted therapy, including the optimal surgical procedure, timing of surgical intervention, and the relationship between surgery and radiotherapy, were examined to provide practical guidance for integrating systemic and local treatment in advanced lung cancer. This focused narrative review was developed by conducting a targeted PubMed search through October 2025 using terms associated with epidermal growth factor receptor, tyrosine kinase inhibitors (TKIs), and salvage or conversion surgery. Relevant studies were selectively examined to explore indications, patient selection, timing of surgery, extent of resection, and comparisons with radiotherapy as an alternative local treatment. Salvage surgery following definitive chemoradiotherapy is intended to cure isolated intrathoracic recurrences and typically excludes patients with uncontrolled distant metastases or unresectable lymph node disease. Conversely, salvage surgery following TKI therapy is increasingly included in strategies for systemic disease control. Its objectives include removing local lesions resistant to systemic treatment, prolonging the effectiveness of systemic therapy, and gathering pathological and genomic information. Importantly, the primary therapeutic goal is to prolong overall survival when performed after TKI therapy, rather than improve disease-free survival. As molecular targeted treatments advance, the role of salvage surgery following TKI therapy is expected to expand. Further evidence is required to guide patient selection, timing of intervention, and surgical strategy.

Giant cell tumor of bone (GCTB) induces overproduction of bone-resorbing osteoclasts through receptor activator of nuclear factor kappa B ligand (RANKL), leading to bone resorption and destruction. Consequently, denosumab, a neutralizing antibody against RANKL (a cytokine essential for osteoclast induction), is used to treat patients with GCTB. However, the activity of bone formation in GCTB remains poorly understood. Here, we show that GCTB antagonizes bone formation by expressing WNT5B, which inhibits bone formation. Co-culture of NCC-GCTB1-C1 (GCTB1s), a human GCTB cell line, with human adipose-derived stem cells (ADSCs) was performed with osteoblast induction medium. To identify the inhibitors of osteoblast differentiation, we reanalyzed the single-cell RNA sequencing data that was previously published. In addition, we performed spatial transcriptome analysis (Visium) against the section of paraffin block of GCTB. The targeted protein was knocked out using CRISPR/Cas9 and co-culture was performed. Co-culture of GCTB1s with ADSCs significantly inhibited mineralization of ADSCs. Reanalysis of single-cell RNA sequencing data indicated that GCTB tumors express WNT5B, and we observed that GCTB1s express WNT5B. We then knocked out WNT5B in GCTB1s using CRISPR/Cas9 and co-cultured them with ADSCs and observed significant rescue of mineralization in ADSCs relative to ADSCs cultured with GCTB1s expressing WNT5B. We also show that ADSC supernatants induce mineralization of GCTB1s. These studies indicate that GCTB not only induces osteoclasts, but also possesses activity that inhibits bone formation.

Although Japan has an established welfare system for individuals with visual impairments, medical-welfare coordination remains limited. To address this gap, the Low Vision Care Hub (LVCH) was established within a university hospital. We evaluated the impact of LVCH on visitor satisfaction before and after consultation STUDY DESIGN: A single-center, one-group pre-post study METHODS: Individuals with self-reported functional vision difficulties who visited LVCH between July 1 and December 20, 2024 were included. Consultation was provided based on seven domains of low vision care outlined by the Japan Society for Low-Vision Research and Rehabilitation. Satisfaction was measured on a custom 6-point ordinal scale (0-5) pre/post consultation. Changes in satisfaction scores were analyzed using the Wilcoxon signed-rank test. Multivariable logistic regression adjusted for potential confounders RESULTS: Ninety-three participants were included. Satisfaction scores significantly increased after consultation (p < .001) and improvements were consistent across sex, age groups, and visual impairment classification using the International Council of Ophthalmology (ICO) criteria (all p < .001). Notably, participants not meeting the ICO-defined low vision criteria also improved (p < .001). On multivariable logistic regression, only older age (≥ 60 years) remained significantly associated with a markedly improved satisfaction score (OR = 2.98, 95% CI 1.10-8.05, p = .03) CONCLUSION: Consultations provided at LVCH significantly improved visitor satisfaction, including those who did not meet the ICO low vision criteria. Consultation may be particularly effective in individuals aged over 60 years. Overall, early-stage intervention through structured consultation may benefit individuals with functional vision difficulties.

Humoral factors regulating cardiac myocytes have not yet been fully elucidated. Using mass spectrometry, we analyzed peptides released from primary neonatal rat cardiac fibroblasts to identify a 24-amino-acid peptide with an intramolecular disulfide bond. It is derived from the C-terminal end of integral membrane protein 2A (ITM2A), a single-pass type II membrane protein; the peptide sequence is identical between humans and rodents and N-terminally flanked by conserved dibasic residues KR. The ITM2A peptide stimulated secretion of atrial natriuretic peptide (ANP), the predominant hormone produced by cardiac myocytes, in a Langendorff rat heart perfusion system as well as a primary culture of neonatal rat ventricular myocytes. These ANP secretion changes were not accompanied by an alteration in the beating rate, a key determinant of ANP secretion. In a mouse cardiac infarction model, both plasma ANP concentration and ITM2A gene expression in heart tissue reached a peak level on day 7 after operation. Our findings provide new insight into cardiac cell-to-cell communication that regulates ANP secretion.

This study aimed to examine the effects of concomitant use of proton-pump inhibitors (PPIs) on the survival outcomes in patients with endocrine-sensitive chemotherapy-naïve advanced breast cancer (BC) treated with palbociclib or abemaciclib. This multicenter, retrospective study was conducted at five hospitals in Japan. Data were collected from consecutive patients treated with palbociclib or abemaciclib in combination with endocrine therapy as first-line treatment for endocrine-sensitive chemotherapy-naïve advanced BC between December 2017 and August 2022. Associations between concomitant PPI use and survival outcomes were analyzed. Among 202 patients, 38 (19%) were concomitant PPI users. In the palbociclib population (n = 123), concomitant PPI use was associated with a trend toward decreased progression-free survival (PFS) and a significant reduction in overall survival (OS; crude hazard ratio [HR], 1.67; 95% confidence interval [CI], 0.86–3.00 and crude HR, 3.51; 95% CI, 1.53–7.64, respectively). In multivariable analyses, consistent results were obtained (adjusted HR, 1.29; 95% CI, 0.66–2.53 and adjusted HR, 3.23; 95% CI, 1.28–7.67, respectively). In contrast, concomitant PPI use did not significantly affect either PFS or OS in the abemaciclib group (n = 79). Concomitant PPI use decreased the efficacy of palbociclib regardless of the formulation, with no such impact observed with abemaciclib.

Collagen fibers are significant constituents of connective tissues such as the skin, bone, and tendons. Their morphology and alignment are essential for understanding tissue function and pathology. Collagen fibers are conventionally observed using optical and electron microscopy, and Second-harmonic generation microscopy. This study introduces a novel microscopic imaging technique, Scattering Angle-Resolved Bioimaging (SARB), which utilizes the scattering properties of unstained specimens. The SARB is based on a conventional optical microscope with a structured illumination module that projects a checker pattern onto the sample. This allows the acquisition of images separated by the scattering angle, enabling the visualization of the scattering characteristics. We applied SARB and electron microscopy to thin, unstained formalin-fixed, paraffin-embedded (FFPE) sections of mouse skin. SARB successfully identified the location of collagen fiber bundles and revealed the scattering information within them. Importantly, these scattering patterns correlated with the orientation of the collagen fibrils, as observed in Transmission Electron Microscopy images. The use of unstained FFPE sections simplifies sample preparation, offering a practical advantage. Additionally, SARB provides access to fine structural information that is often difficult to obtain using conventional optical microscopy. These findings suggest that SARB has strong potential as a label-free, morphology-sensitive imaging method for evaluating fibrosis.

Approximately 30% of patients with schizophrenia do not respond to antipsychotics. While schizophrenia has been primarily explained by the dopamine dysfunction hypothesis, treatment-resistant schizophrenia (TRS) may involve a different pathophysiology. Neuromelanin (NM), a product of dopamine metabolism in the substantia nigra (SN), indirectly measures long-term dopamine synthesis capacity. Few studies have examined SN NM levels in TRS. Therefore, we investigated the relationship between SN NM levels and treatment responsiveness in schizophrenia. We included age- and sex-matched TRS, patients with schizophrenia in remission of positive symptoms (SZ-R), and healthy controls (HCs). Neuromelanin-sensitive magnetic resonance imaging was used to measure SN NM signals. We also evaluated clinical symptoms and cognitive impairment. We conducted voxel-wise analyses of NM contrast-to-noise ratio (CNR) to compare groups pairwise. Correlation analyses examined relationships between NM signals and symptom severity. Seventy-two participants (n = 24 per group) completed the study. The TRS group had higher dorsal SN CNR than the HC group (510 out of 1948 voxels at p < 0.05, corrected p = 0.005, permutation test). In contrast, no significant differences were observed in the other comparisons. No significant correlations were found between NM CNR and clinical severity. Our findings contrast with previous positron emission tomography studies on dorsal striatal dopamine function. Since the dorsal SN contributes to both the mesolimbic and nigrostriatal pathways, with a relatively greater role in the former, dopamine functions in these pathways may play different roles for treatment responsiveness. Further research with multimodal imaging is needed to examine dopamine function and antipsychotic treatment responsiveness in schizophrenia.