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Geogenic contaminants, such as arsenic, are often found in soil recovered from coastal areas. These contaminants may leach out when the soil is used as embankment material. Moreover, the leaching of such contaminants might be influenced by environmental changes, such as dry-wet cycles, and higher environmental risks due to a larger amount of leaching are anticipated in some cases. In this study, therefore, soil recovered from tsunami deposits was subjected to dry-wet cycles under three different drying conditions to investigate how environmental changes affect the leaching behavior. To evaluate the physical and chemical changes in the soil surface, microscopic/spectroscopic studies were conducted. Batch leaching tests revealed that dry-wet cycles slightly alter the leaching behavior of most elements, such as Fe, Si, Na, Ca, etc. Arsenic leaching was seen to increase in certain dry-wet cycles before decreasing, and microscopic/spectroscopic confirmed that this increase was likely due to pyrite oxidation. These dry-wet cycles can disintegrate pyrite morphology and cause pyrite oxidation, leading to a more acidic leaching condition that accelerates arsenic leaching. After a certain oxidation procedure, the resulting ferric hydroxide may prevent the pyrite surfaces from further oxidation. The Fe oxides and hydroxides can also act as arsenic adsorbents, preventing the increase in arsenic concentration. [ABSTRACT FROM AUTHOR]

The leaching behavior of arsenic and boron is evaluated in this work through two types of excavated rocks with geogenic contaminants under different temperatures. Excavated rocks with geogenic contaminants are expected to be used in embankments with appropriate countermeasures being taken against the risks brought about by geogenic contamination. The leaching behavior might change because of changes in the ground temperature. However, the effects of temperature on the leaching behavior of such rocks have not been well examined. Herein, batch leaching tests at temperatures between 5 and 60 °C were performed under shaking and nonshaking conditions. Mudstone and shale rock were crushed into particles smaller than 2 mm, which were required for the tests. The tests were carried out for durations ranging from 6 h to 15 days because changes in leaching kinetics also require careful evaluation. After conducting the nonshaking tests for 15 days at 40 °C, the mudstone sample leached arsenic and boron at concentrations of approximately 0.7 and 1.0 mg/L, respectively. The arsenic and boron concentrations were about 20 and 40% higher than those of the sample leached at a temperature of 20 °C. Elevated temperatures were seen to increase the leaching kinetics of the toxic elements. For the shale rock sample, the leaching rate for arsenic was 7.7 × 10-2/h at 40 °C, which was about 2.5 times greater than the value at 30 °C. The nonshaking tests showed higher leaching amounts of arsenic and boron than the shaking tests, especially at elevated temperatures. As unrealistic estimations should be avoided, nonshaking tests are suggested. Moreover, nonshaking tests lasting longer than 6 h are necessary due to the relatively slow dissolution of minerals. [ABSTRACT FROM AUTHOR]

An attenuation layer composed of ground mixed with stabilising agents can prevent the contamination of the surrounding area when using soils and rocks with geogenic contaminants in embankments. The optimum particle size of the stabilising agent must be selected based on the requirements of the construction site because the mechanical and chemical properties of the attenuation layer are site-specific. However, the relationship between the particle size of the stabilising agent and the attenuation performance of soil–agent mixtures has yet to be fully clarified. This study employs batch sorption tests to evaluate the attenuation of arsenic by a soil mixed with a calcium–magnesium composite with different particle sizes, ranging from powder particles (<0.075 mm in size) to granular particles with diameters between 2.0 and 9.5 mm. Amended soil more effectively attenuates the contaminant than the original soil. In one experiment, a stabilising agent of granular particles (between 2.0 and 9.5 mm) for the amendment increased the soil's partition coefficient K d from 14.5 to 22.2 cm3/g, which is more than a 50% improvement in the attenuation. Using a stabilising agent with a smaller particle size for the amendment has a greater impact. K d increases linearly as the particle size of the stabilising agent decreases down to 0.075 mm. Using the K d from laboratory tests, simulations with a one-dimensional advection–dispersion equation demonstrate the durability of the attenuation layer. Both the powder and the granular particles show promise as attenuation layer materials. [ABSTRACT FROM AUTHOR]

Lenvatinib was recently approved as a novel first-line molecular targeted agent (MTA) for treating hepatocellular carcinoma (HCC). The importance of relative dose intensity (RDI) has been shown in the treatment of various types of cancers. However, RDI may not accurately reflect the treatment intensity of lenvatinib, as it is the first oral MTA where the dose is based on the patient's weight. We aimed to evaluate the utility of 2M-DBR (the delivered dose intensity/body surface area ratio at 60 days) by comparing the relationship between 2M-DBR, 2M-RDI (RDI at 60 days), and the therapeutic response. The therapeutic response to lenvatinib was evaluated in 45 patients who underwent computed tomography 8–12 weeks after treatment initiation. We also investigated the clinical factors associated with high 2M-DBR. The area under the receiver operating characteristic of 2M-DBR that predicts the response to lenvatinib was higher than that of 2M-RDI (0.8004 vs. 0.7778). Patients with high 2M-DBR achieved significantly better objective responses and disease control rates than those with low 2M-DBR (p < 0.0001 and 0.0008). Patients with high 2M-DBR experienced significantly longer progression-free survival (PFS) than those with low 2M-DBR (p = 0.0001), while there was no significant correlation between 2M-RDI levels and PFS (p = 0.2198). Patients who achieved higher levels of 2M-DBR had a significantly better modified ALBI grade (p = 0.0437), better CONUT score (p = 0.0222), and higher BTR (p = 0.0281). Multivariate analysis revealed that high 2M-DBR was the only significant factor associated with longer PFS. In conclusion, 2M-DBR could be an important factor that reflects treatment intensity and useful for predicting the response to lenvatinib against HCC, instead of 2M-RDI. [ABSTRACT FROM AUTHOR]

Aim: The diagnosis of drug‐induced liver injury (DILI) is challenging. We modified the revised electronic version of the Roussel Uclaf Causality Assessment Method (RUCAM) for the diagnosis of DILI (RECAM), the scoring system developed in US and Spanish cohorts in 2022, and developed RECAM‐J 2023 to align with the clinical practice in Japan. In the current study, we introduce RECAM‐J 2023 and verify its performance in the context of Japanese patients with DILI. Methods: After translation of RECAM into Japanese, modifications were made to develop RECAM‐J 2023 without any alteration to the scores. To examine the validity and performance of RECAM‐J 2023, clinical information on DILI and non‐DILI cases in Japan were retrospectively collected. The diagnosis of DILI was made by expert's decision. Then we scored each case using RECAM‐J 2023, and calculated area under curve (AUC) values for identification for DILI. Results: We collected data from 538 DILI and 128 non‐DILI cases. The sum of highly probable (HP) and probable (PR) cases categorized by RECAM‐J 2023 were only 206 (38%) in DILI cases. As the primary cause of low scores was the deduction with missing hepatitis virus markers, which is unlikely to be an issue in prospective applications, we rescored without these deductions. At this time, the sum of HP and PR was raised to 421 (78%). The AUCs of RECAM‐J 2023 without deductions were 0.70 and 0.88 for identifying at least HP, and at least PR, respectively. Conclusion: RECAM‐J 2023, when prospectively used without any missing hepatitis virus markers, provides acceptable performance for identifying at least PR DILI cases in Japanese daily clinical practice. [ABSTRACT FROM AUTHOR]

Aim: Combined hepatocellular‐cholangiocarcinoma (cHCC‐CCA) is a rare primary liver cancer that has two different tumor phenotypes in a single tumor nodule. The relationship between genetic mutations and clinicopathological features of cHCC‐CCA remains to be elucidated. Methods: Whole‐exome sequencing analyses were carried out in 13 primary and 2 recurrent cHCC‐CCAs. The whole‐exome analyses and clinicopathological information were integrated. Results: TP53 was the most frequently mutated gene in this cohort, followed by BAP1, IDH1/2, and NFE2L2 mutations in multiple cases. All tumors with diameters <3 cm had TP53 mutations. In contrast, six of seven tumors with diameters ≥3 cm did not have TP53 mutations, but all seven tumors had mutations in genes associated with various pathways, including Wnt, RAS/PI3K, and epigenetic modulators. In the signature analysis, the pattern of mutations shown in the TP53 mutation group tended to be more similar to HCC than the TP53 nonmutation group. Mutations in recurrent cHCC‐CCA tumors were frequently identical to those in the primary tumor, suggesting that those tumors originated from identical clones of the primary cHCC‐CCA tumors. Recurrent and co‐occurrent HCC tumors in the same patients with cHCC‐CCA had either common or different mutation patterns from the primary cHCC‐CCA tumors in each case. Conclusions: The study suggested that there were two subtypes of cHCC‐CCA, one involving TP53 mutations in the early stage of the carcinogenic process and the other not involving such mutations. The comparison of the variants between primary and recurrent tumors suggested that cHCC‐CCA was derived from an identical clone. [ABSTRACT FROM AUTHOR]

The attenuation layer method has been considered an effective countermeasure to deal with excavated soils and rocks containing geogenic toxic elements like arsenic (As). The geosynthetic sorption sheet is a geosynthetic product that can be employed in the attenuation layer method applications as a sorption material. The sorption sheets used in the attenuation layer will be inevitably subjected to overburdened loads in the field. In this study, laboratory column experiments are conducted to evaluate the attenuation performance of the geosynthetic sorption sheets coated with hydrotalcite as sorbent against As under different overburden pressure conditions (10, 100, and 200 kPa). Experimental results showed that the cumulative sorption masses of As for 200 kPa cases are approximately 10.5–13.3 times greater than that for 10 kPa cases. Microstructure characterizations of the geosynthetic sorption sheet before and after loading were also detected. More compacted and involved fiber configuration as a result of higher loading produces a more effective contact between As solution and hydrotalcite. The presence of partial dissolution of hydrotalcite is confirmed through the chemical analysis of effluent. However, hydrotalcite would gradually become stable during continuous use. • Geosynthetic sorption sheet is a promising material applied in the attenuation layer method. • Compressive stress is beneficial in the sorption performance of geosynthetic sorption sheets. • Compacted fabric structure caused by loadings can effectively promote arsenic sorption. • Geosynthetic sorption sheet is more efficient in As(V) sorption compared with As(III). • Mineral stability of hydrotalcite-based material in an aqueous matrix deserves attention. [ABSTRACT FROM AUTHOR]

• We present a rare case of donor-origin intrahepatic cholangiocarcinoma in a liver allograft after hepatocellular carcinoma transplantation. • The tumor was derived from the donor according to fluorescence in situ hybridization and whole exome sequencing analysis. • Donor-origin cancer after liver transplantation is extremely rare, but it must be considered to provide proper treatment. Tumors may develop in the grafted liver after liver transplantation for hepatocellular carcinoma, most of which are hepatocellular carcinoma recurrences and are rarely of donor origin. We report a rare case of donor-origin intrahepatic cholangiocarcinoma in a liver allograft after liver transplantation for hepatocellular carcinoma. A man in his 60s underwent liver transplantation for hepatocellular carcinoma with hepatitis C virus cirrhosis. The donor was a braindead woman in her 60s who had no history of malignancy. Three years and 5 months after liver transplantation, a tumor developed in the allograft. Computed tomography scans showed a 40-mm tumor that was atypical for hepatocellular carcinoma. Tumor biopsy was most suggestive of intrahepatic cholangiocarcinoma. Fluorescence in situ hybridization of the tumor showed an XX signal pattern, suggesting that it originated from the donor liver. Whole exome sequencing analysis strongly suggested that the tumor was an intrahepatic cholangiocarcinoma derived from the donor. Although donor-origin cancer after liver transplantation is extremely rare, it should be considered for adequate treatment. [ABSTRACT FROM AUTHOR]