Tokyo Metropolitan Komagome Hospital

Pancreatic cancer remains one of the most lethal malignancies, with a 5-year survival rate of less than 9 %, primarily due to its aggressive metastasis and drug resistance. Circulating tumor cells (CTCs), which are key mediators of metastasis, are critical for understanding these clinical challenges. In this study, we applied a single-cell transcriptome analysis platform combining a microcavity array (MCA) and gel-based cell manipulation (GCM) technique for marker-independent cell recovery to analyze CTCs from patients with metastatic pancreatic cancer. Using pancreatic cancer cell lines, we demonstrated that this microcavity-gel manipulation platform enables high-quality single-cell RNA sequencing while preserving intrinsic molecular characteristics. Furthermore, spiking experiments with cancer cells in blood confirmed that the process minimizes contamination from non-target blood cells. Application of this platform to patient-derived CTCs revealed that most CTCs exhibited epithelial-mesenchymal transition (EMT)-like features and high expression of platelet-related genes such as PF4 and PPBP, suggesting platelet-driven EMT activation. In addition, CTCs were consistently arrested in the G1 phase of the cell cycle, implying a potential survival mechanism under therapeutic stress. These findings highlight the utility of microcavity-gel manipulation platform for robust single-cell transcriptomic profiling and provided novel insights into the biology of pancreatic CTCs.

Objective IgG4-related disease (IgG4-RD) is a systemic condition that frequently involves multiple organs. This study examined the utility of diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) for the diagnosis and monitoring of IgG4-RD. Methods Twenty patients underwent DWIBS for the diagnosis of IgG4-RD. Of these, six did so after steroid therapy. The extent of high-intensity areas visible on DWIBS was compared to that on computed tomography (CT). Changes in signal enhancement and apparent diffusion coefficient (ADC) values on DWIBS were analyzed following steroid therapy. Results In addition to 20 main IgG4-RD lesions, areas of high intensity were detected on DWIBS in 28 lesions in 8 organs and the retroperitoneum. The high-intensity areas on DWIBS also appeared as a mass or thickness on CT, except in three areas in the kidneys and retroperitoneum, but segmental wall thickness of the bile duct in two patients was undetectable on DWIBS. On the second DWIBS procedure following steroid therapy, all 16 high-intensity areas displayed some degree of improvement, including complete resolution (n=3), disappearance of high signal intensity and a decrease in the size of the lesion (n=6), and a decrease in both signal intensity and lesion size (n=7). Furthermore, the ADC value of 13 areas significantly increased after steroid therapy (1.32±0.24×10^-3 mm²/s vs. 1.68±0.25×10^-3 mm²/s; p<0.05). Conclusion DWIBS can readily detect IgG4-RD lesions throughout the body simultaneously and provide information about disease activity and therapeutic effects. DWIBS is an indispensable tool in the treatment of IgG4-RD.

This study evaluated the dose calculation accuracy of a Monte Carlo (MC)-based independent dose calculation system (IDCS) for CyberKnife brain stereotactic treatment plans and compared it with ray-tracing (RT) and MC algorithms within the MultiPlan treatment planning system (TPS). Beam modeling accuracy was validated for 11 circular fields using measured output factors (OPF), percentage depth dose (PDD), and off-center ratio (OCR). A total of 200 retrospective brain stereotactic treatment plans were analyzed (50 prescribed 23 Gy in 1 fraction, 50 prescribed 35 Gy in 3 fractions, and 100 prescribed 41.5 Gy in 5 fractions). Among these, 24 quality assurance (QA) plans were evaluated using homogeneous cylindrical phantoms and ionization chambers. Dose-volume histogram (DVH) was calculated, and gamma analysis (3%/1 mm, 10% threshold) was performed. IDCS aligned with measured data, with OPF and PDD/OCR errors within 3% and 4%, respectively, except for small-field underestimations in the build-up region. For QA plans, TPS overestimated the measured dose (RT: 0.5% ± 2.6%, p = 0.58, MC: 1.7% ± 3.1%, p = 0.07), while IDCS underestimated it (- 1.3% ± 2.3%, p = 0.07). Gamma passing rates were 98.9% ± 1.5% (TPS-RT vs. IDCS) and 99.9% ± 0.3% (TPS-MC vs. IDCS). DVH metrics (planning target volume [PTV]: D_98%, D_95%, and D_2%) showed clinically acceptable differences. IDCS showed greater dose calculation accuracy than the TPS-RT algorithm and could identify dose discrepancies in specific cases, thereby confirming its reliability for CyberKnife QA.