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Steller sea lions (SSLs) migrate to the Hokkaido coast to spend the winter there, leading to conflicts arising with fishermen over herring. This study analyzed the trends in the SSLs’ use of a haulout as a rest site under human pressure. From January to March in 2017, 2018, and 2019, we recorded the SSL behavior at the haulout site off Otaru City, Hokkaido, for 24 h a day using a fixed-point video recorder. We investigated three years of data to analyze the relationships between the SSL behaviors (attendance/landing–entry timings/remaining on land) and herring caught. We also monitored the SSL behaviors during changes in weather conditions and under human pressure. Throughout the three years, the SSLs used the haulout site during harsher weather or under human pressure. In 2017 and 2018, there was a correlation between the herring caught and the maximum number of SSLs on the haulout, but not in 2019. The number of SSLs on the haulout increased from evening to night; most individuals entered the water in the morning. The SSLs probably return to the water around sunrise not only for foraging but also to avoid anthropogenic pressure. The damage caused to the herring fishery by the SSLs was severe, but it is also clear that human pressure changed their behavior in response.

Abstract Background Although rare, cytomegalovirus (CMV) reactivation can be lethal in patients with cancer. However, the criteria for the prevention of cytomegalovirus reactivation during cancer treatment are unclear. This study aimed to identify factors associated with CMV reactivation in patients with esophageal cancer who were receiving chemoradiotherapy. Methods This retrospective study included esophageal cancer patients receiving definitive or palliative chemoradiotherapy during April 2013–March 2020. Patients with fever during chemoradiotherapy underwent a systemic work‐up to detect the primary focus of infection, and CMV antigenemia was assessed in cases of unidentifiable infection. Results Among 132 patients (80.3% male, median age 69 years [range, 39–86 years]), 124 received 5‐fluorouracil plus cisplatin and 8 received oxaliplatin–5‐fluorouracil–levofolinate chemotherapy. Overall, 19 patients had CMV reactivation, 37 had other infections, and 76 had no identified infection (groups 1, 2, and 3, respectively). Median minimum lymphocyte counts were 81.0/µl (interquartile range: 52.0–144.0/µl), 120.0/µl (81.0–162.5/µl), and 185.5/µl (120.5–328.0/µl) in groups 1, 2, and 3, respectively, with counts being significantly lower in groups 1 and 2 than in group 3 (p

BackgroundWe previously reported that a high tumor burden is a prognostic factor based on an analysis of 26 patients with radioactive iodine-refractory differentiated thyroid cancer (RR-DTC) who were treated with lenvatinib. However, the optimal tumor burden for starting lenvatinib still remains to be defined. The aim of this retrospective study was to further explore in the same patient cohort the optimal timing for the start of lenvatinib by focusing on the pre- and post-treatment tumor burden.MethodsThe 26 patients were treated with lenvatinib from 2012 to 2017. We explored the optimal timing for the start of lenvatinib by comparing the characteristics of long-term responders who were defined as patients with progression-free survival ≥ 30 months and non-long-term responders.ResultsLong-term responders had a smaller post-treatment tumor burden at maximum shrinkage than non-long-term responders. Further, post-treatment tumor burden had a strong linear correlation with baseline tumor burden. We created an estimation formula for baseline tumor burden related to prognosis, using these regression lines. Patients with a sum of diameters of target lesions < 60 mm or maximum tumor diameter < 34 mm at baseline were estimated to have significantly better survival outcomes.ConclusionsWe found a strong linear correlation between pre- and post-treatment tumor burden. Our results suggested a cut-off value for baseline tumor burden for long-term prognosis among patients treated with lenvatinib.

Standard therapy for radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) is multi-targeted kinase inhibitors (m-TKIs), represented by sorafenib and lenvatinib. One of the main target molecules of m-TKIs is vascular endothelial growth factor receptor (VEGF-R). m-TKIs are known to cause adverse reactions such as hypertension and proteinuria as a class effect. In particular, proteinuria is thought to result from vascular endothelial damage and podocytopathy in glomeruli, and the development of thrombotic microangiopathy (TMA) has been reported for VEGF inhibitors. We encountered a patient with RAI-refractory (RR) papillary thyroid carcinoma (PTC) who developed proteinuria and renal dysfunction due to lenvatinib. Renal biopsy demonstrated that these changes were caused by TMA. To our knowledge, this is the first reported case of TMA due to lenvatinib in a Japanese patient with RR-PTC. A 70-year-old woman developed proteinuria, renal impairment and hypertension while receiving lenvatinib for RR-PTC. Her proteinuria and renal damage continued to worsen despite dose reductions and dose interruptions. Renal biopsy was consistent with the chronic type of TMA. These findings indicate that TMA is a possible cause of proteinuria due to lenvatinib, as has been reported for the VEGF inhibitors.

Simple Summary: The Steller sea lion (SSL) is the largest Otariidae family species widely distributed in the cold North Pacific Ocean. SSLs also migrate to Hokkaido, Japan, in the winter. SSLs travel south along the Sea of Japan coast for winter to catch the herring that spawn near the coast. SSLs utilize haulouts as rest sites during herring season, but this can be affected by weather- and human-related pressures. In this study, we investigated the haulout use patterns of SSLs and the effect of human disturbance over a period of three years. The behavior of the SSLs on the haulouts differed from when they were on rookeries. Furthermore, the number of SSLs on the haulout and the duration of time they spent there reduced from the first year (lower human pressure) to the third year (human presence increased). Based on these findings, the SSLs may adjust the timing of when they enter the water to around sunrise, following the ecology of the herring and to avoid human disturbance. Therefore, it is necessary to continue investigating the relationship between the ecology of the SSLs and environmental changes in order to determine the damage that the SSLs cause to fishery interests. Steller sea lions (SSLs) migrate to the Hokkaido coast to spend the winter there, leading to conflicts arising with fishermen over herring. This study analyzed the trends in the SSLs' use of a haulout as a rest site under human pressure. From January to March in 2017, 2018, and 2019, we recorded the SSL behavior at the haulout site off Otaru City, Hokkaido, for 24 h a day using a fixed-point video recorder. We investigated three years of data to analyze the relationships between the SSL behaviors (attendance/landing–entry timings/remaining on land) and herring caught. We also monitored the SSL behaviors during changes in weather conditions and under human pressure. Throughout the three years, the SSLs used the haulout site during harsher weather or under human pressure. In 2017 and 2018, there was a correlation between the herring caught and the maximum number of SSLs on the haulout, but not in 2019. The number of SSLs on the haulout increased from evening to night; most individuals entered the water in the morning. The SSLs probably return to the water around sunrise not only for foraging but also to avoid anthropogenic pressure. The damage caused to the herring fishery by the SSLs was severe, but it is also clear that human pressure changed their behavior in response. [ABSTRACT FROM AUTHOR]

We evaluated the neutron bang time in fast-ignition inertial confinement fusion and the response function of deuterium-deuterium (DD) neutrons for burn history monitoring applications with a single-crystal CVD diamond detector. Signals were successfully obtained for the first time with a single-crystal diamond detector for DD neutrons of above 108 neutrons/shot. [ABSTRACT FROM AUTHOR]

We report a mediastinal germ cell tumor (GCT) that exhibited a discrepancy between the time course of serum human chorionic gonadotropin (hCG) levels and clinical consequences. An otherwise healthy man, aged 34 years, was diagnosed with a nonseminomatous GCT, most likely embryonal carcinoma (EC), based on a mediastinal tumor biopsy. Standard chemotherapy resulted in an optimal decrease in serum hCG levels. However, multiple lesions in the liver continued to enlarge, which led to his death. Autopsy revealed few viable tumor cells in the liver, with the great majority of the tumor cells appearing to have undergone necrosis, suggesting that they responded to the chemotherapy. The residual tumor cells in the mediastinum and the liver were similar to syncytiotrophoblast cells, suggesting a choriocarcinoma (CC). On immunohistochemical analysis, the mediastinal tumor cells in the diagnostic biopsy specimen expressed both CD30 and hCG, whereas residual mediastinal and hepatic tumor cells in the autopsy specimen after chemotherapy also expressed hCG, but not CD30. These findings suggested that the patient suffered from a primary mixed GCT consisting of an EC and a CC. Both pre- and postchemotherapy tumors strongly expressed matrix metalloproteinase-2, supporting the aggressive and invasive features of the tumor phenotype. We speculate that the extremely invasive tumor destroyed normal liver structure, whereas chemotherapy and central necrosis reduced the number of viable cells themselves, causing a discordant decrease in serum hCG levels.

Objectives: The irinotecan (CPT-11) + 5-fluorouracil (5-FU)/leucovorin (LV) + UFT/LV chemotherapy, in which repetitive oral administration of UFT/LV replaces the infusion of 5-FU/LV in the FOLFIRI regimen, has been proposed previously. In this study, five of 10 patients were injected with a bolus of 5-FU and the other were not injected with it in order to examine the effect of omitting it in terms of pharmacokinetics of 5-FU.Methods: The treatment consisted of the intravenous infusions of CPT-11 at 100 mg/m2 and l-LV at 15 mg/m2, and the injection of a bolus of 5-FU at 500 mg/m2 on day 1, and the repetitive oral administration of UFT/LV (300 mg/m2/day as tegafur + 75 mg/day of LV) on days 1-5. A total of 13 measurements of the plasma concentrations of uracil, 5-FU and tegafur were made per patient within 48 hr after the start of chemotherapy and the value of area under the concentration-time curve (AUC0-48) was evaluated. The plasma concentration was also determined at 2 weeks to assess long-term exposure to 5-FU.Results: The plasma concentrations of 5-FU at 24 hr after the start of treatment were 27.4 ng/mL and 9.4 ng/mL in the patients with and without the bolus injection, respectively. At 48 hr, they were 31.3 ng/mL and 10.4 ng/mL with the AUC0-48 values of 22.16 mg*h/L and 0.65 mg*h/L, respectively. The 5-FU was detected in the plasma at 226 hr after the last administration of UFT/LV for the patients with the bolus injection, but not for those without.Conclusion: A bolus of 5-FU on day 1 provided long-term exposure to 5-FU.

Objective: The effects of dose-escalation of 5-fluorouracil (5-FU) on the clinical outcome and pharmacokinetics of 5-FU were investigated in Japanese patients with Stage III/IVa esophageal squamous cell carcinoma. Methods: Thirty-five patients with Stage III/IVa were enrolled, who were treated with a definitive 5-FU/cisplatin-based chemoradiotherapy. A course consisted of continuous infusion of 5-FU at 400 mg/m2/day (the standard dose group, N=27) or 500-550 mg/m2/day (the high dose group, N=8) for days 1-5 and 8-12, infusion of cisplatin at 40 mg/m2/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week interval. Plasma concentrations of 5-FU were determined by high performance liquid chromatography at 5:00 PM on days 3, 10, 38 and 45, and at 5:00 AM on days 4, 11, 39 and 46. Results and conclusions: No patient with Stage IVa achieved a complete response in the standard dose group, whereas a complete response was observed at a rate of 50% in the high dose group, and this can be explained by a higher plasma concentration of 5-FU. The circadian rhythm in the concentrations found at the standard dose was not observed for a higher dose.

Objective: The effects of replacing cisplatin (CDDP) with cis-diammineglycolatoplatinum (nedaplatin, NDP), a second-generation platinum complex, on the pharmacokinetics of 5-fluorouracil (5-FU) were investigated in Japanese patients with esophageal squamous cell carcinoma, who were treated with a definitive 5-FU/CDDP-based chemoradiotherapy. Methods: Fifty-six patients were enrolled, 49 treated with CDDP and 7 treated with NDP. A course consisted of continuous infusion of 5-FU at 400 mg/m2/day for days 1-5 and 8-12, infusion of CDDP or NDP at 40 mg/m2/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week interval. Plasma concentrations of 5-FU were determined by high performance liquid chromatography at 5 PM on days 3, 10, 38 and45, and at 5 AM on days 4, 11, 39 and 46. Results and conclusions: The circadian rhythm in plasma concentrations of 5-FU observed in the case of CDDP was altered when NDP was used instead. The clinical response can be predicted by monitoring plasma concentrations of 5-FU in the CDDP group, but not in the NDP group.