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We aimed to identify prognostic predictive factors of patients with penile squamous cell carcinoma (PSCC). This retrospective study reviewed the clinical and pathological data of patients with PSCC at 10 institutions in Japan between January 2008 and December 2019. The primary endpoint was cancer-specific survival (CSS). We also identified useful predictive factors for CSS in patients with PSCC. In total, 64 patients with PSCC were enrolled. At the end of the follow-up period, 15 patients (23.4%) died owing to PSCC and six (9.4%) died owing to other causes. The 2- and 3-year CSS rates were 78.9% and 76.6%, respectively. Using the Kaplan–Meier method, the Eastern Cooperative Oncology Group performance status 0, serum albumin levels ≥4.2 g/dL, hemoglobin levels ≥13.2 g/dL, C-reactive protein levels

We conducted a multicenter, retrospective study to evaluate the efficacy and safety of combination nivolumab plus ipilimumab (NIVO+IPI) in 35 patients with advanced or metastatic renal cell carcinoma (mRCC). In this study, we focused on patients who received NIVO+IPI and were stratified into intermediate- or poor-risk disease according to the International Metastatic Renal Cell Carcinoma Database Consortium model at five institutions in Japan. The primary endpoint was overall survival (OS). Secondary endpoints were disease control rate (DCR), best overall response (BOR), objective response rate (ORR), and progression-free survival (PFS). In addition, we evaluated the role of inflammatory cell ratios, namely neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as predictive biomarkers in patients with mRCC. The median follow-up period was 1 year, and the 1-year OS rate was 95.8%. The ORR and DCR were 34.3% and 80.0%, respectively. According to BOR, four patients (11.4%) achieved complete response. According to NLR stratification, the 1-year PFS rates were 82.6% and 23.7% when the NLR was ≤4.6 and >4.6, respectively (p = 0.04). Based on PLR stratification, the 1-year PFS rates were 81.7% and 34.3% when the PLR was ≤188.1 and >188.1, respectively (p = 0.033). Although 71.4% of the patients experienced treatment-related adverse events (TRAEs) with NIVO+IPI, only four patients discontinued NIVO+IPI due to grade 3/4 TRAEs. Patients treated with NIVO+IPI as a first-line therapy for advanced or mRCC achieved relatively better oncological outcomes. Therefore, NIVO+IPI may have potential advantages and may lead to a treatment effect compared to those receiving targeted therapies. In addition, PLR >188.1 may be a useful predictive marker for mRCC patients who received NIVO+IPI.

We evaluated the efficacy and safety of combination therapy with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKI) as first-line therapy for patients diagnosed as having advanced or metastatic renal cell carcinoma (mRCC). We enrolled 51 patients to receive ICI+TKI therapy for mRCC at 9 Japanese institutions. The overall survival (OS) of the patients treated with ICI+TKI was the primary endpoint., and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Furthermore, we analyzed the clinical prognostic and predictive factors in patients with mRCC treated with ICI+TKI therapy. Seven months was the median follow-up period. The OS rates at 6, 12, and 18 months were 93.1, 82.5, and 68.8%, respectively. The median PFS for patients who received ICI+TKI was 19.0 months, ORR was 68.6%, and DCR was 88.2%. ICI+TKI-related adverse events occurred in 43 patients (84.3%) with any grade and in 22 patients (43.1%) with grade ≥3. Treatment selection with poor prognostic factors may be prudent, even though ICI+TKI is an efficacious and safe first-line treatment in patients with mRCC.

A multicenter retrospective study was conducted to evaluate the efficacy and safety of cabozantinib in patients with advanced or metastatic renal cell carcinoma (mRCC). We enrolled 53 patients with mRCC who received cabozantinib at eight institutions in Japan. The primary endpoint was overall survival (OS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). In addition, we analyzed prognostic factors in patients with mRCC treated with cabozantinib. The median follow-up period was 8 months, and the median OS was 20.0 months. The ORR and DCR were 39.6% and 83.0%, respectively. The median PFS was 11.0 months. PFS was significantly shorter in patients previously treated with at least two tyrosine kinase inhibitors and in those with C-reactive protein (CRP) ≥ 1.27 mg/dL (p = 0.021 and p = 0.029, respectively). Adverse events of any grade and grades ≥3 occurred in 42 (79.2%) and 10 (18.9%) patients, respectively. Cabozantinib is a useful treatment option for patients with mRCC and may benefit from earlier use. In this study, CRP ≥ 1.27 mg/dL is a poor prognostic factor in patients treated with cabozantinib, and careful follow-up may be required in treating patients with high CRP.

This study aimed to evaluate the effectiveness and safety of molecular-targeted therapies (MTTs) after the discontinuation of nivolumab and ipilimumab (NIVO+IPI) combination therapy in patients who had been diagnosed with advanced/metastatic renal cell carcinoma as real-world outcomes. We enrolled patients treated with MTTs following initial therapy with NIVO+IPI at nine institutions in Japan. We evaluated the objective response rate (ORR) as the primary endpoint and disease control rate (DCR), best overall response, and oncological outcomes (overall survival (OS) and progression-free survival (PFS)) as the secondary endpoints. We also evaluated factors predictive of disease progression after the administration of MTTs. Patients were followed up for a median of 8 months. The ORR was 44.8%, and the DCR was 72.4%. The median OS and PFS of MTTs after NIVO+IPI were 18 months and 8 months, respectively. A total of 31% of patients experienced grade 3/4 MTT-related adverse events. The median PFS in patients with bone metastases was significantly shorter than that in those without bone metastases (4 vs. 12 months, p = 0.012). MTTs may be a useful secondary treatment option after the discontinuation of NIVO+IPI.

Background/Aim: A genomic analysis based on next-generation sequencing is important for deciding cancer treatment strategies. Cancer tissue sometimes displays intratumor heterogeneity and a pathologic specimen may contain more than two tumor grades. Although tumor grades are very important for the cancer prognosis, the impact of higher tumor grade distribution in a specimen used for a genomic analysis is unknown. Patients and Methods: We retrospectively analyzed the data of 61 clear cell carcinoma and 46 prostate cancer patients that were diagnosed between December 2018 and August 2022 using the GeneRead Human Comprehensive Cancer Panel or SureSelect PrePool custom Tier2. Genome annotation and curation were performed using the GenomeJack software. Results: Tumor mutation burden (TMB) was increased in proportion to the higher tumor grade distribution in grade 2 clear cell renal cell carcinoma (ccRCC). In PC, Grade Group 3/4 specimens that included an increased distribution of Gleason pattern 4 had more frequent gene mutations. Conclusion: Our results suggest the importance of selecting the maximum distribution of higher tumor grade areas to obtain results on the precise gene alterations for genomics-focused treatments. [ABSTRACT FROM AUTHOR]

Introduction A patient undergoing hemodialysis and being treated with everolimus for metastatic epithelioid angiomyolipoma has never been described in the literature, to our knowledge. Case presentation A 53‐year‐old woman who had undergone trans‐arterial embolization for epithelioid angiomyolipoma was referred with a chief complaint about right knee pain. Hemodialysis had been started after the embolization. Needle biopsy specimens of tumors obtained from behind the right kidney and in the right femur were diagnosed as epithelioid angiomyolipoma metastases. The patient underwent treatment with everolimus and achieved a partial response after 6 months of treatment without serious adverse events. Conclusion Everolimus might be effective for patients with metastatic epithelioid angiomyolipoma who are undergoing hemodialysis.

Biochar (BC) is used as a soil amendment to enhance plant growth by improving mainly soil chemical and hydrophysical properties. In this work the effects of two types of BCs on soil water retention properties were analysed. The first type of BC was made from sugarcane bagasse. It was added to a clay "Shimajiri Maji" soil at an application rate of 3 w%. The second type of BC was made from paper fiber sludge and grain husks. It was added into a loam soil at rates of 3.6, and 7.3 w%. It was assumed that the effect of BC amendment will be more pronounced in coarse-grained soil than in fine-grained one. Therefore, the second type of BC was applied additionally in the silica sand, in a textured contrast material compared with the loam soil. The BC amendment caused statistically significant increase of water content in the transmission pores of the clay soil, in the storage pores of the loam soil, and in the macropores and the storage pores in the silica sand. Despite of the positive effect on soil water retention, statistically significant increase of available water capacity (AWC) was identified only in the loam soil with the larger BC amendment rate. Possible reasons are discussed.

The aim of this study was to assess the utility of neutrophil-to-lymphocyte ratio (NLR), plate-let-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) as predictive biomarkers with oncological outcomes for metastatic renal cell carcinoma (mRCC) patients treated with nivolumab and ipilimumab (NIVO + IPI). We conducted a retrospective multicenter cohort study assessing patients with mRCC treated with NIVO + IPI at eight institutions in Japan. In this study, the follow-up period was median 14 months. The 1-year overall- and progression-free survival (PFS) rates were 89.1% and 63.1, respectively. The objective response rate (ORR) and disease control rate (DCR) were 41.9% and 81.4%, respectively. The 1-year PFS rates were 85.7% and 49.1% for NLR ≤ 2.8 and >2.8, respectively (p = 0.005), and 75.5% and 49.7% for PLR ≤ 215.6 and >215.6, respectively (p = 0.034). Regarding SII, the 1-year PFS rates were 90.0% and 54.8% when SII was ≤561.7 and >561.7, respectively (p = 0.023). Therefore, NLR, PLR, and SII levels in mRCC patients treated with NIVO + IPI may be useful in predicting oncological outcomes.

Abstract Background Exosomes or extracellular vesicles have the potential as a diagnostic marker for various diseases including cancer. In order to identify novel exosomal markers for prostate cancer (PC), we performed proteomic analysis of exosomes isolated from PC cell lines and examined the usefulness of the marker in patients. Methods Exosomes isolated by differential centrifugation from the culture medium of androgen-dependent LNCaP prostate cancer cell line and its sublines of partially androgen-independent C4, androgen-independent C4–2 and bone metastatic C4–2B were subjected to iTRAQ-based proteomic analysis. Exosomes were also isolated by immunocapture and separated by size exclusion chromatography and density gradient centrifugation. Protein expression was determined by Western blot analysis. GGT activity was measured using a fluorescent probe, γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG). Immunohistochemical analysis of tissues was performed using anti-GGT1 antibody. Results Among proteins upregulated in C4–2 and C4–2B cells than in LNCaP cells, we focused on gamma-glutamyltransferase 1 (GGT1), a cell-surface enzyme that regulates the catabolism of extracellular glutathione. The levels of both GGT1 large and small subunits were elevated in exosomes isolated from C4–2 and C4–2B cells by differential centrifugation and by immunocapture with anti-CD9 or -prostate-specific membrane antigen (PSMA) antibody. In cell lysates and exosomes, GGT1 expression correlated with GGT activity. Size exclusion chromatography of human serum demonstrated the presence of GGT activity and GGT1 subunits in fractions positive for CD9. Density gradient centrifugation revealed the co-presence of GGT1 subunits with CD9 in exosomes isolated by differential centrifugation from human serum. Since GGT activity correlated with GGT1 expression in serum exosomes isolated by differential centrifugation, we measured serum exosomal GGT activity in patients. Unexpectedly, we found that serum exosomal GGT activity was significantly higher in PC patients than in benign prostatic hyperplasia (BPH) patients. In support of this finding, immunohistochemical analysis showed increased GGT1 expression in PC tissues compared with BPH tissues. Conclusions Our results suggest that serum exosomal GGT activity could be a useful biomarker for PC.

The time domain reflectometry (TDR) method measures the soil apparent permittivity (), which is the basis for estimation of soil volumetric water content (θ) via an empirical calibration equation or dielectric mixing model. The relationship between and θ [i.e., (θ)] in soils with significant volumetric fractions of bound water and with bimodal pore-size distributions displays a distinct increase in slope after θ exceeds a threshold value. The interpretation of this change in slope has been aided with application of dielectric mixing models through the inclusion of a bound water phase and/or θ-dependent changes in phase configuration. However, measured with time-domain reflectometry (TDR) in soils with significant volumetric fractions of bound water has been previously observed to change as a function of the effective frequency of the soil-attenuated bandwidth. Therefore, the main objective of this work was to investigate the influence of bound water and phase configuration in four, high-surface-area Japanese Andisols with bimodal pore-size distributions using dielectric mixing models alone or coupled with a dielectric damping model. Soil-specific (θ) relationships were measured in the laboratory using standard methods and were simulated with two frequency-independent, real-valued dielectric mixing models and a complex-valued, frequency-dependent model coupled with a dielectric damping model. The results of the simulations indicate that frequency-dependent dielectric permittivity of the bound water phase significantly influences TDR-measured (θ), suggesting that soil- and probe-specific calibrations may be required for soils with significant volumetric fractions of bound water.

Physicochemical properties of biochar, which are used as a soil amendment material in agricultural fields, are different depending on biomass feedstock and pyrolysis processes. In this study, we evaluated the influence of feedstock type and pyrolysis temperature on the water-retention related properties of biochar. Wood-chips [cedar (CE) and cypress (CY)]; moso bamboo (MB); rice husk (RH); sugarcane bagasse (SB); poultry manure (PM) and agricultural wastewater sludge (WS) were each pyrolysed at 400, 600 and 800 °C with a retention time of two hours. Scanning electron microscopy micrographs (SEM), hydrophobicity indices, pore-size distribution measured by mercury-intrusion porosimetry, water-retention curves (WRCs) and plant-available water capacities (AWCs) of the biochars were measured to evaluate their potentials as soil-amendment materials for improving soils’ water-retention. As the pyrolysis temperature was increased, the hydrophobicity index decreased. On the other hand, pyrolysis temperature did not affect the distribution of micrometre-range pores, which are useful for plant-available water, of biochars. The AWCs of the biochars formed from CE, CY and SB were greater than those produced from other feedstocks, at 600 and 800 °C. Therefore, we can suggest that the biochars derived from wood-chips (CE and CY) and SB have greater potential for enhancing soils’ water-retention.

A 26-year-old woman with gross hematuria was seen in a previous hospital. Magnetic resonance imaging (MRI) showed a tumor at the dome of the urinary bladder with invasion outside of the bladder wall. The patient underwent transurethral resection of the bladder tumor (TUR-BT). From the result of the pathological examination, the tumor was suggested to be carcinosarcoma of the bladder. The patient was then referred to our hospital for treatment. We performed radical cystectomy and ileal conduit diversion. Pathological examination of the excised specimen revealed an inflammatory myofibroblastic tumor as the basis for immunostaining of anaplastic lymphoma kinase (ALK).

Background/Aim: The Von Hippel-Lindau (VHL) gene encodes a protein (pVHL) that plays an important role in proteasome degradation of hypoxia inducible factor α (HIFα) through E3 activation. Accumulation of HIFα by loss of functional pVHL promotes tumorigenesis, thus, VHL has tumor suppressor gene capability in clear cell renal cell carcinoma (ccRCC). VHL is the most frequently mutated gene in ccRCC. The complete loss of VHL is mainly achieved by loss of chromosome 3p, which has a VHL coding region in combination with mutation or hypermethylation of the remaining copy of VHL. Given the risk of constitutional chromosome 3 translocation for RCC, it is important to detect the translocation and understand the mechanism underlying the development of multifocal ccRCC. Case Report: A 67-year-old female patient diagnosed with multifocal RCC underwent robot-assisted partial nephrectomy (RAPN) for three kidney tumors. A cancer gene panel test using next generation sequencing (NGS) detected differential VHL mutations (c.533T>G; p.L178R, c.465_466insTA; p.T157Ifs*3, c.343C>A; p.H115N), while VHL mutation was not detected in peripheral blood DNA. A tendency toward copy number loss of genes on der(3) was also detected in all tumors, but not in the germline one. A karyotype analysis revealed a germline translocation between 3 and 6, t(3;6)(q12;q14). Conclusion: Chromosome 3 translocation and loss of derivative chromosome containing 3p and subsequent somatic differential VHL mutations in this case strongly support the previously proposed three-step model to explain the development of familial conventional ccRCC. [ABSTRACT FROM AUTHOR]

Biochar (BC) is used as a soil amendment to enhance plant growth by improving mainly soil chemical and hydrophysical properties. In this work the effects of two types of BCs on soil water retention properties were analysed. The first type of BC was made from sugarcane bagasse. It was added to a clay "Shimajiri Maji" soil at an application rate of 3 w%. The second type of BC was made from paper fiber sludge and grain husks. It was added into a loam soil at rates of 3.6, and 7.3 w%. It was assumed that the effect of BC amendment will be more pronounced in coarse-grained soil than in fine-grained one. Therefore, the second type of BC was applied additionally in the silica sand, in a textured contrast material compared with the loam soil. The BC amendment caused statistically significant increase of water content in the transmission pores of the clay soil, in the storage pores of the loam soil, and in the macropores and the storage pores in the silica sand. Despite of the positive effect on soil water retention, statistically significant increase of available water capacity (AWC) was identified only in the loam soil with the larger BC amendment rate. Possible reasons are discussed. [ABSTRACT FROM AUTHOR]