The efficacy of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) has been reported, but insertion of fiducial markers in the liver is usually required. We evaluated the efficacy and toxicity of respiratory-gated PBT without fiducial markers for HCC located within 2 cm of the gastrointestinal tract. From March 2011 to December 2015 at our institution, 40 patients were evaluated (median age, 72 years; range, 38–87 years). All patients underwent PBT at a dose of 60 to 80 cobalt gray equivalents (CGE) in 20 to 38 fractions. The median follow-up period was 19.9 months (range, 1.2–72.3 months). The median tumor size was 36.5 mm (range, 11–124 mm). Kaplan–Meier estimates of the 2-year overall survival, progression-free survival, and local tumor control rates were 76%, 60%, and 94%, respectively. One patient (2.5%) developed a grade 3 gastric ulcer and one (2.5%) developed grade 3 ascites retention; none of the remaining patients developed grade >3 toxicities (National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.0.). This study indicates that PBT without fiducial markers achieves good local control without severe treatment-related toxicity of the gastrointestinal tract for HCC located within 2 cm of the gastrointestinal tract.

An experimental setup of an air shower array, hadron calorimeter, and emulsion chamber is being carried out at Mt. Chacaltaya (5200 m, Bolivia), in order to study the hadron interaction and the primary cosmic rays in the energy region exceeding ${10}^{15}$ eV. The number of hadrons in the air shower, detected by the hadron calorimeter, is discussed mainly in this paper. A comparison with the simulation shows that the number of hadrons in the air shower is not compatible with that of the simulation, indicating that the Feynman scaling law is violated more strongly than the one assumed in the simulation at ${10}^{16}$ eV. The average mass number of the primary cosmic rays, estimated from the distribution of the number of hadrons, is $〈\ln A〉=2.8\mathrm{}\pm 0.5$ at ${10}^{16}$ eV.

At the Fukui Prefectural Hospital Proton Therapy Center, neutron doses behind the concrete shields and at the maze were measured with three types of radiation monitors (DARWIN, Wendi-2, and a rem meter) along with solid-state nuclear track detectors. The measured data were compared with estimations of analytical models and the Monte Carlo code, Particle and Heavy-Ion Transport code System (PHITS). The analytical model, using the parameters employed in the shielding design of the facility, gave considerably larger values than the measured data. This means that the facility was designed with a sufficient margin of safety. The results calculated by PHITS were less than those of the analytical model and were about three times larger than the measured data. From a perspective that seeks conservative estimation with less margin, the Monte Carlo simulation is a good tool for shielding design of accelerator-based proton treatment facilities.

Proton beam therapy (PBT) achieves good local control for hepatocellular carcinoma (HCC), and toxicity tends to be lower than for photon radiotherapy. Focal liver parenchymal damage in radiotherapy is described as the focal liver reaction (FLR); the threshold doses (TDs) for FLR in the background liver have been analyzed in stereotactic ablative body radiotherapy and brachytherapy. To develop a safer approach for PBT, both TD and liver volume changes are considered clinically important in predicting the extent of damage before treatment, and subsequently in reducing background liver damage. We investigated appearance time, TDs and volume changes regarding FLR after PBT for HCC. Patients who were treated using PBT and were followed up using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA MRI) after PBT were enrolled. Sixty-eight lesions in 58 patients were eligible for analysis. MRI was acquired at the end of treatment, and at 1, 2, 3 and 6 months after PBT. We defined the FLR as a clearly depicted hypointense area on the hepatobiliary phase of Gd-EOB-DTPA MRI, and we monitored TDs and volume changes in the FLR area and the residual liver outside of the FLR area. FLR was depicted in all lesions at 3 months after PBT. In FLR expressed as the 2-Gy equivalent dose (α/β = 3 Gy), TDs did not differ significantly (27.0±6.4 CGE [10 fractions [Fr] vs. 30.5±7.3 CGE [20 Fr]). There were also no correlations between the TDs and clinical factors, and no significant differences between Child-Pugh A and B scores. The volume of the FLR area decreased and the residual liver volume increased, particularly during the initial 3 months. This study established the FLR dose for liver with HCC, which might be useful in the prediction of remnant liver volume for PBT.

Objective: The adhesive interaction of monocytes and vascular smooth muscle cells (VSMCs) has been suggested to be a regulatory signal in the cellular activation that is involved in the pathogenesis of atherosclerosis. We investigated the effects of monocyte–VSMC interaction on inducible nitric oxide (NO) synthase expression. Methods: NO production by the cultured cells was determined by measuring the nitrite content of the culture media using the Griess reagent. The expression of inducible NO synthase protein was assayed by Western blotting. Results: Interleukin-1β (IL-1β) induced nitrite production by VSMCs in a time-dependent manner. The addition of the mouse monocyte cell line J774 to IL-1β-stimulated VSMCs further increased nitrite production in a monocyte number-dependent manner. Enhanced nitrite production by coculture was accompanied by increased inducible NO synthase protein accumulation. Addition of tumor necrosis factor-α (TNF-α) also enhanced IL-1β-induced nitrite production by VSMCs, but TNF-α showed no effect in the presence of monocytes. Coculture of monocytes and VSMCs in the presence of IL-1β secreted substantial amounts of TNF-α. The production of nitrite by coculture was markedly inhibited by an anti-TNF-α antibody. Conclusions: The present study revealed that direct cell-to-cell interaction between monocytes and VSMCs enhances NO production, suggesting an important role for their interaction in the pathogenesis of atherosclerosis.