Accompanied by the development of systemic therapy for metastatic renal cell carcinoma, the concept of focal treatment, including surgical treatment, has been changing. Although immediate ...cytoreductive nephrectomy was essentially considered for synchronous metastatic renal cell carcinoma patients, the CARMENA trial and SURTIME trial revealed the negative impact of immediate cytoreductive nephrectomy. Therefore, immediate cytoreductive nephrectomy is currently considered only for a limited number of patients. Besides, deferred cytoreductive nephrectomy seems to have efficacy for overall survival in prior retrospective studies. Two randomized controlled trials, the PROBE trial (NCT04510597) and the NORDIC‐SUN trial (NCT03977571), are underway to elucidate deferred cytoreductive nephrectomy. Metastasectomy is also considered in metastatic renal cell carcinoma patients because previous studies demonstrated the overall survival benefit of metastasectomy. However, since all reports were retrospective studies, physicians could exclude the patients who were not expected to show the efficacy of metastasectomy. Therefore, an adequate patient selection for metastasectomy is important. A common factor predicting better overall survival was complete resection. Radiotherapies for metastatic lesions during systemic therapy showed approximately 90% local disease control rate at 1 year. However, no report has demonstrated that radiotherapy improves survival so far. Since surgical and focal treatments for metastatic renal cell carcinoma patients generally have minimal evidence, further investigations are needed.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The aims of this study were to investigate prognosis and validate prognostic models Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic Renal Cell Carcinoma Data ...Consortium (IMDC), and Japanese metastatic renal cancer (JMRC) models in the targeted therapy era in Japanese patients with metastatic renal cell carcinoma.
Methods
We retrospectively analyzed 692 patients who were diagnosed with mRCC from January 2008 to August 2018 in the Michinoku Japan Urological Cancer Study Group database. Nivolumab as sequential therapy was widely used. Other immune checkpoint inhibitors were excluded from this study.
Results
The median overall survival (95% confident interval) in all, MSKCC favorable, intermediate, and poor risk patients was 41.0 months (33.9–46.8), not reached (63.5 to not estimable), 46.8 months (37.1–52.9), and 10.4 months (8.9–14.4), respectively. The median overall survival (95% confident interval) in IMDC favorable, intermediate, and poor risk patients was not reached (61.6 to not estimable), 47.4 months (41.4–56.5), and 11.5 (9.9–16.3), respectively. The c-index of the MSKCC, IMDC, and JMRC models calculated at mRCC diagnosis was 0.680, 0.689, and 0.700, respectively. No statistical differences were found in the c-index among the models.
Conclusion
While the real-world overall survival in Japanese patients with mRCC in the targeted therapy era improved compared to that previously reported in the cytokine era, there was no clear difference in the survival of poor risk patients between these eras. There were no differences in the superiority among the models.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We report a case of bacteremia caused by Bacillus subtilis variant natto after a gastrointestinal perforation in a patient in Japan. Genotypic and phenotypic studies of biotin identified B. subtilis ...var. natto. This case and 3 others in Japan may have been caused by consuming natto (fermented soybeans).
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The phase 3 JAVELIN Renal 101 trial of avelumab + axitinib vs sunitinib in patients with treatment‐naive advanced renal cell carcinoma (RCC) demonstrated significantly improved progression‐free ...survival (PFS) and higher objective response rate (ORR) with the combination vs sunitinib. Japanese patients enrolled in the study (N = 67) were randomized to receive avelumab + axitinib (N = 33) or sunitinib (N = 34); 67% vs 59% had PD‐L1+ tumors (≥1% of immune cells) and 6%/64%/27% vs 6%/82%/12% had International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable/intermediate/poor risk status. In patients who received avelumab + axitinib vs sunitinib, median PFS (95% confidence interval CI) was not estimable (8.1 months, not estimable) vs 11.2 months (1.6 months, not estimable) (hazard ratio HR, 0.49; 95% CI, 0.152, 1.563) in patients with PD‐L1+ tumors and 16.6 months (8.1 months, not estimable) vs 11.2 months (4.2 months, not estimable) (HR, 0.66; 95% CI, 0.296, 1.464) in patients irrespective of PD‐L1 expression. Median overall survival (OS) has not been reached in either arm in patients with PD‐L1+ tumors and irrespective of PD‐L1 expression. ORR (95% CI) was 60.6% (42.1%, 77.1%) vs 17.6% (6.8%, 34.5%) in patients irrespective of PD‐L1 expression. Common treatment‐emergent adverse events (all grade; grade ≥3) in each arm were hand‐foot syndrome (64%; 9% vs 71%; 9%), hypertension (55%; 30% vs 44%; 18%), hypothyroidism (55%; 0% vs 24%; 0%), dysgeusia (21%; 0% vs 56%; 0%) and platelet count decreased (3%; 0% vs 65%; 32%). Avelumab + axitinib was efficacious and tolerable in treatment‐naive Japanese patients with advanced RCC, which is consistent with results in the overall population.
The phase 3 JAVELIN Renal 101 trial of avelumab + axitinib vs sunitinib in patients with treatment‐naive advanced renal cell carcinoma (RCC) demonstrated significantly improved progression‐free survival (PFS) and higher objective response rate (ORR) with the combination vs sunitinib. In Japanese patients who received avelumab + axitinib vs sunitinib, median PFS (95% CI) was not estimable (8.1 months, not estimable) vs 11.2 months (1.6 months, not estimable) (HR, 0.49; 95% CI, 0.152, 1.563) in patients with PD‐L1+ tumors and 16.6 months (8.1 months, not estimable) vs 11.2 months (4.2 months, not estimable) (HR, 0.66; 95% CI, 0.296, 1.464) in patients irrespective of PD‐L1 expression. Avelumab + axitinib was efficacious and tolerable in treatment‐naive Japanese patients with advanced RCC, which is consistent with results in the overall population.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Accurate optical monitors are critical for automating operations of fiber-optic networks. Deep neural network (DNN) based optical monitors have been investigated as accurate optical monitors to ...leverage a large amount of data obtained from fiber-optic networks. Although DNN-based optical monitors have been trained and tested to ensure the given accuracy criteria, this does not ensure sufficient accuracy under unexpected conditions, that is, out of test conditions, e.g., a newly developed modulation format that is not included in the test dataset. Thus, it is necessary to prepare a monitor to assess the current accuracy of a DNN-based optical monitor's output for robust automation of networks. We present a DNN-based optical monitor that simultaneously outputs an optical signal-to-noise ratio and its uncertainty information using a dropout method at the inference phase. This monitor was evaluated in cases in which the DNNs were trained with either a limited number of records or partially missing records in a training dataset. The proposed monitor successfully informed that own output has large uncertainties due to a limited amount of training data or a missing part in training dataset. Additionally, to improve an accuracy of estimated uncertainty, the number of partial neural networks by dropout at the inference phase was optimized. This is a valuable step toward designing robust "self-driving" optical networks.
Background
The decline of health-related quality-of-life (QOL) during the year after radical prostatectomy is severe. General self-efficacy (GSE) is an effective psychological factor for long-term ...regulation of patient behavior and emotions. GSE is expected to facilitate enhanced health-related quality of life. We evaluated changes in GSE and analyzed the relationship between GSE and prostate cancer-specific and general health-related QOL.
Methods
We conducted a longitudinal survey with 104 patients who underwent radical prostatectomy and administered the General Self-efficacy Scale (GSES), Expanded Prostate Cancer Index Composite (EPIC), and SF8 Health Survey (SF-8). ANCOVA was performed to compare EPIC and SF-8 between GSES high and low-medium groups.
Results
GSES scores increased significantly after 6 months. Regarding EPIC urinary summary scores, high GSES group was significantly higher than low-medium group at 1 month (mean score difference MSD, 7.3; 95% CI 1.1–13.2,
P
= 0.016), 3 months (MSD, 6.8; 95% CI 0.7–12.8,
P
= 0.028), and 6 months (MSD, 6.3; 95% CI 0.9–11.7,
P
= 0.022). High GSES group had significantly higher SF-8 physical component summary score at 6 months (MSD, 3.2; 95% CI 1.4–5.0,
P
= 0.001), and significantly higher SF-8 mental component summary score at 1 month (MSD, 2.6; 95% CI 0.4–4.9,
P
= 0.022), 3 months (MSD, 2.7; 95% CI 0.8–4.6,
P
= 0.007), and 6 months (MSD, 2.8; 95% CI 1.0–4.6,
P
= 0.003).
Conclusion
This study suggests that high GSE was associated with better prostate cancer-specific and general health-related QOL after radical prostatectomy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Several clear cell renal cell carcinoma (ccRCC) cases harbour fibroblast growth factor receptor 4 (FGFR4) gene copy number (CN) gains. In this study, we investigated the functional contribution of ...FGFR4 CN amplification in ccRCC.
The correlation between FGFR4 CN determined via real-time PCR and protein expression evaluated using western blotting and immunohistochemistry was assessed in ccRCC cell lines (A498, A704, and 769-P), a papillary RCC cell line (ACHN), and clinical ccRCC specimens. The effect of FGFR4 inhibition on ccRCC cell proliferation and survival was assessed via either RNA interference or using the selective FGFR4 inhibitor BLU9931, followed by MTS assays, western blotting, and flow cytometry. To investigate whether FGFR4 is a potential therapeutic target, a xenograft mouse model was administered BLU9931.
60% of ccRCC surgical specimens harboured an FGFR4 CN amplification. FGFR4 CN was positively correlated with its protein expression. All ccRCC cell lines harboured FGFR4 CN amplifications, whereas ACHN did not. FGFR4 silencing or inhibition attenuated intracellular signal transduction pathways, resulting in apoptosis and suppressed proliferation in ccRCC cell lines. BLU9931 suppressed tumours at a tolerable dose in the mouse model.
FGFR4 contributes to ccRCC cell proliferation and survival following FGFR4 amplification, making it a potential therapeutic target for ccRCC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pulmonary hypertension (PH) is commonly associated with left heart disease. In this retrospective study, using the database of a clinical study conducted between January 2008 and July 2008, the ...phenotypes of PH were classified using non-invasive cardiac acoustic biomarkers (CABs) and compared with classification by echocardiography. Records with same-day measurement of acoustic cardiography and right heart catheterization (RHC) parameters were included; cases with congenital heart disease were excluded. Using the RHC measurements, PH was classified as pre-capillary PH (Prec-PH), isolated post-capillary PH (Ipc-PH), and combined pre-capillary and post-capillary PH (Cpc-PH). The first, second, third, and fourth heart sounds (S1, S2, S3, and S4) were quantified as CABs (intensity, complexity, and strength). Forty subjects were selected: 5 had Prec-PH, 5 had Ipc-PH, 8 had Cpc-PH, and 22 had No-PH. CABs were significantly correlated with RHC measurements, with significant differences among phenotypes. Phenotype classification was performed using various CABs, and the diagnostic performance as assessed by the area under the receiver operating characteristic curve was 0.674–0.720 for Prec-PH, 0.657–0.807 for Ipc-PH, and 0.742 for Cpc-PH. High negative and low positive predictive values for phenotype identification were observed. CABs may provide an ambulatory measurement method with home-monitoring friendliness which is more convenient than standard examinations to identify presence of PH and its phenotypes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PURPOSE:
METHODS:
RESULTS:Of 1,977 patients with rectal cancers, 930 underwent pelvic sidewall dissection without adjuvant radiotherapy. Positive lateral lymph nodes were found in 129. Multivariate ...analysis disclosed a significantly increased incidence of positive lateral lymph nodes in female gender, lower rectal cancers, non-well-differentiated adenocarcinoma, tumor size of ≥4 cm and T3-T4. The five-year survival rate for 1,977 patients was 79.7 percent. The survival of patients with positive lateral lymph nodes was significantly worse than that of Stage III patients with negative lateral lymph nodes (45.8 vs. 71.2 percent, P<0.0001). Multivariate analysis showed significantly worse prognosis in male gender, pelvic sidewall dissection, lower rectal cancers, T3-T4, perirectal lymph node metastasis, and positive lateral lymph nodes. During the median follow-up time of 57 months, recurrence developed in 19.7 percent17 percent in negative and 58.1 percent in positive lateral lymph nodes (P<0.0001). Local recurrence was found in 8 percent6.8 percent in negative and 25.6 percent in positive lateral lymph nodes (P<0.0001). Multivariate analysis disclosed that lower rectal cancers, non-well-differentiated adenocarcinoma, T3-T4, perirectal lymph node metastasis, and positive lateral lymph nodes were significantly associated with an increased local recurrence.
CONCLUSIONS:
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KISLJ, NUK, OILJ, PNG, SAZU, UL, UM, UPUK
Macrolides (MCs) are broad-spectrum antimicrobials with activity against many microorganisms. They are widely used, and the development of MC-resistant bacteria is a serious problem in Japan. It is ...therefore necessary to clarify the purpose and duration of administration, with the aim of promoting appropriate use.
Patients of all ages, for whom oral MCs were prescribed between 2016 and 2020 were included. They were divided into four groups based on the number of days per prescription. In the long-term treatment group, patients treated with MCs for ≥1000 days were specifically investigated for the purpose of treatment.
Macrolide prescriptions increased from 2019 to 2020. Most patients received ≥28 days of treatment based on one prescription. During the study period, 1212 patients (28.6%) received a total of ≥50 days and 152 patients (3.6%) received a total of ≥1000 days of treatment. Approximately a third of long-term administrations were for nontuberculous mycobacterial infections (NTMs), and 18.3% of patients with NTMs were treated with MCs alone. In addition, many MCs were administered for their anti-inflammatory effects on neutrophils.
Owing to their pleiotropic effects, MCs may also be administered for the treatment of noninfectious diseases. In general, the long-term administration of antimicrobials contradicts the strategy for the suppression of resistant bacteria. It is thus important to understand the actual clinical utility of MCs and the purpose and duration of administration. In addition, strategies for the appropriate use of MCs are required for each medical institution.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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