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Objective: To investigate the prognosis and prognostic factors of patients with metastatic renal cell carcinoma who underwent metastasectomy. Methods: We sent questionnaires to Japanese hospitals. The questionnaires included data of patients with metastatic renal cell carcinoma who had their metastatic lesions removed between January 1988 and December 2009. We collected them and retrospectively analyzed these data and calculated the overall survival from the first metastasectomy until death or last follow-up. We also analyzed the relationship between survival and clinico-pathologic features and determined adverse prognostic factors. Furthermore, we identified a poor prognostic group by counting the number of prognostic factors. Results: A sample size of 556 patients from 48 institutions was studied. The median overall survival was 80 months. Four adverse prognostic factors were detected: incomplete resection by metastasectomy (hazard ratio [HR], 2.15), brain metastasis (HR, 3.73), >1.0 mg/dL C-reactive protein (HR, 2.45), and the highest histologic grade in Japanese classification (nuclei of tumor cells are larger than nuclei of normal tubular cells; HR, 1.88). The median overall survivals of patients with 3 or 4 prognostic factors, 2 factors, and 0 and 1 factors were 10 months, 42 months, and 105 months, respectively. Conclusion: Four adverse prognostic factors for predicting the survival of patients with removed metastases were identified. Patients with 3 or 4 of these adverse prognostic factors had a worse prognosis. [Copyright &y& Elsevier]

Abstract: Background: Incidence rate of renal cell carcinoma (RCC) differs among countries. The rates of Asian countries are lower than those of countries in North America or Europe but are exceptionally high in Japanese males. Approximately 30% of patients with RCC have metastasis at initial diagnosis, and another 30% have metastasis after nephrectomy. Clinical studies of risk factors in patients with metastatic RCC (mRCC) are mainly based on data from non-Asian patients. Objectives: We aimed to investigate the prognosis of Japanese patients and their prognostic factors. Design, setting, and participants: The subjects of this study were 1463 patients who were clinically diagnosed with RCC with metastasis in 40 Japanese hospitals between January 1988 and November 2002. Measurements: The primary end point was overall survival calculated from first diagnosis of mRCC to death or last follow-up. We also investigated the relationship between survival and clinical features. Results and limitations: The median overall survival time was 21.4 mo. The estimated survival rates at 1, 3, 5, and 10 yr were 64.2%, 35.2%, 22.5%, and 9.1%, respectively; they contrasted with data from the United States of 54%, 19%, 10%, and 6%, respectively for the same periods. A high percentage of patients had undergone nephrectomy (80.5%) and metastasectomy (20.8%), both of which were shown to prolong survival. Conclusions: The median survival time in the present study was approximately twice as long as that of previous studies from North America or Europe. Early diagnosis of metastasis, nephrectomy, metastasectomy, and cytokine-based therapy seemed to improve the prognosis of RCC patients in the present study. [Copyright &y& Elsevier]

3D-HDTV is regarded as the high-definition image application to succeed HDTV. Narrowband real-time transmission of 3D-HDTV is expected to be implemented by highly efficient compression techniques that utilize the features of a stereoscopic moving image. In this paper, the principal objectives are to reduce the image quality differences between the channels and to develop more advanced element technologies based on disparity compensation. Within the MPEG-2 multiview profile framework, which is the international standard for stereoscopic coding, a 3D-HDTV moving image coding scheme was investigated and its performance evaluated based on simulation test results. First, in addition to introducing common buffer control given the objective of reducing the image quality difference between the channels, the optimum GOP setting for 3D-HDTV coding is explained. Furthermore, advanced techniques for motion estimation and rate control implemented based on disparity compensation are proposed and shown to be effective in implementing highly efficient 3D-HDTV coding. © 2001 Scripta Technica, Electron Comm Jpn Pt 1, 85(2): 51–60, 2002 [ABSTRACT FROM AUTHOR]

It remains unknown whether the early response to vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR‐TKI) management in malignancies links to long‐term survival. The objective of this study was to investigate the survival rates and predictive factors of early response in patients with metastatic renal cell carcinoma (mRCC) managed by VEGFR‐TKIs. From Jan. 2008 to Oct. 2018, 496 patients were treated with VEGFR‐TKIs as first‐line treatment at the eight Japanese hospitals (Michinoku RCC). Early cessation was defined as VEGFR‐TKIs being given up within 3 months after their initiation. The number of patients in early cessation VEGFR‐TKIs (Cohort I) was 173 (34.9%), and in long‐term use (Cohort II) was 323 (65.1%). The cancer‐specific survival (CSS) and overall survival (OS) were better in Cohort II. IMDC Poor‐risk was at risk of early cessation of a first‐line VEGFR‐TKI. Axitinib was the most preferred drug for long‐term treatment. On closer examination, both Cohort I and II were divided into two groups, the patients ceased VEGFR‐TKI due to adverse events (Group A [67 from Cohort I] and Group C [51 from Cohort II]) and disease progression (Group B [106 from Cohort I] and Group D [272 from Cohort II]). Despite that the cessation was adverse events, CSS and OS in Group A were worse than both Group C and D. Axitinib was administered with the safer profile. IMDC Poor risk was the risk factor for the early disease progression. Managing early adverse events may contribute to a better prognosis in mRCC patients treated VEGFR‐TKIs. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions We evaluated whether a history of low‐dose rituximab treatment affected herpes zoster development after living kidney transplantation.We enrolled 103 living kidney transplant recipients. Patients were divided into two groups according to their history of rituximab treatment; rituximab was administered to 50 living kidney transplant recipients. We assessed the difference in herpes zoster events between the two groups and determined the risk factors for herpes zoster using multivariate regression analysis.The total dose of rituximab in each kidney transplant recipient who received rituximab therapy was 200–400 mg. The rate of herpes zoster events after transplantation in recipients who received rituximab therapy (4 of 50, 8%) was not higher than that in recipients who did not receive rituximab (9 of 53, 17%) (p = 0.238). Herpes zoster‐free survival did not significantly differ between the two groups (p = 0.409). In the multivariate regression analysis, the association between varicella zoster vaccination before transplantation and herpes zoster events after transplantation was confirmed, whereas rituximab therapy was not associated with herpes zoster events.Low‐dose rituximab therapy in kidney transplant recipients did not influence herpes zoster development after transplantation. Varicella zoster vaccination before transplantation may play an important role in preventing herpes zoster after transplantation. [ABSTRACT FROM AUTHOR]

Background: Kidney transplantation (KT) leads to body composition change, particularly increasing the fat mass. However, limited researches have focused on the long-term follow-up of these changes and factors influencing body composition after KT. Methods: This study evaluated body composition in 31 adult KT recipients, measuring body mass index (BMI), the psoas muscle mass index (PMI) representing muscle mass, visceral and subcutaneous adipose tissue (VAT and SAT) representing fat mass, and skeletal muscle radiodensity (SMR) representing muscle quality before KT and at 2, 4, and 6 years posttransplantation using computed tomography. Linear mixed models (LMM) analyzed temporal changes and contributing factors, while growth curve models assessed influence of these factors on body composition changes posttransplantation. Results: Following KT, BMI, and PMI remained stable, while SAT increased significantly, revealing a 1.30-fold increase from baseline 2 years after transplantation. Similarly, a substantial increase in VAT was observed, with a 1.47-fold increase from baseline 2 years after transplantation with a further 1.75-fold increase 6 years after transplantation. In contrast, SMR decreased with a 0.86-fold decrease from baseline after 2 years. VAT increase was significantly influenced by the interaction between posttransplantation and dialysis duration. Growth curve models confirmed this interaction effect persistently influenced VAT increase posttransplantation. Conclusions: The study revealed that KT promoted significant alterations in body composition characterized by increase in the VAT and SAT and a decline in SMR. Notably, dialysis duration and its interaction with posttransplantation duration emerged as significant factors influencing VAT increase. [ABSTRACT FROM AUTHOR]

Data on the outcomes of third- or fourth-line therapy for metastatic renal cell carcinoma (mRCC) are limited. The aim of our study was to evaluate the efficacy of therapy beyond the second line. We retrospectively analysed data of mRCC patients who underwent systemic therapy at Yamagata University Hospital. The best objective response (BOR), response rate (RR), and progression-free survival (PFS) were assessed for each line of treatment. To investigate the correlation between overall survival (OS) and the number of treatment lines during a patient's lifetime, the median OS was assessed using univariate and multivariate analyses. In the first-, second-, and third-line therapies, approximately 20% of patients had long PFS of >15 months. In targeted treatments beyond the third line, only one treatment suppressed disease progression for >10 months. Among patients who died during the follow-up period, those treated with triple and quadruple lines had similar OS (42.5 months vs. 48.4 months, respectively). Multivariate analysis showed that patients with triple or more lines of therapy had better OS; however, quadruple or more lines of therapy was not an independent prognostic factor. We concluded that third-line systemic therapy could improve OS; however, fourth-line therapy could not. [ABSTRACT FROM AUTHOR]

Although combination immune checkpoint inhibitor (immuno‐oncology [IO]) therapy is the first‐line treatment for metastatic renal cell carcinoma (mRCC), it mostly causes resistance and tumor regrowth. Therefore, an optimal second‐line therapy is necessary. Such therapy typically comprises vascular endothelial growth factor receptor‐tyrosine kinase inhibitors (VEGFR‐TKIs). This study was aimed at comparing the efficacy of two TKIs—axitinib and sunitinib—in mRCC patients. From January 2008 to October 2018, we registered 703 mRCC patients from 8 Japanese institutes. Of these, 408 patients received axitinib or sunitinib as the first‐line treatment. Thereafter, efficacy and survival rate were compared between the axitinib and sunitinib groups. To reduce the effects of selection bias and potential confounders, propensity score matching analysis was performed. Axitinib and sunitinib were administered in 274 and 134 patients, respectively. More than 25% of the patients received nivolumab sequence therapy. To calculate the propensity scores for each patient, we performed multivariate logistic regression analysis. The objective response rate, progression‐free survival (PFS), cause‐specific survival, and overall survival (OS) were significantly better in the axitinib group than in the sunitinib group. Furthermore, the OS was better in the nivolumab‐treated patients in the axitinib group. Axitinib showed higher efficacy and afforded greater survival benefits than did sunitinib when administered as first‐line therapy in mRCC patients. Thus, from among VEGFR‐TKIs, axitinib might be a possible option for application in the middle of IO drug‐based treatment sequences. [ABSTRACT FROM AUTHOR]

Background: Nivolumab plus ipilimumab (NIVO + IPI) is the first-line treatment for patients with metastatic renal cell carcinoma (mRCC). While approximately 40% of patients treated with NIVO + IPI achieve a durable response, 20% develop primary resistance with severe consequences. Therefore, there is a clinical need for criteria to select patients suitable for NIVO + IPI therapy to optimize its therapeutic efficacy. Accordingly, our aim was to evaluate the association between candidate biomarkers measured before treatment initiation and survival. Methods: This was a multi-institutional, retrospective, cohort study of 183 patients with mRCC treated with systematic therapies between August 2015 and July 2023. Of these, 112 received NIVO + IPI as first-line therapy: mean age, 68 years; men, 83.0% (n = 93), and clear cell histology, 80.4% (n = 90). Univariable and multivariable analyses were used to evaluate associations between biomarkers and survival. Results: On univariate analysis, high C-reactive protein and systemic index, a high neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio, and a low lymphocyte-to-monocyte ratio (LMR) were associated with shorter overall survival (OS). On multivariable analysis, a LMR ≤ 3 was retained as an independent factor associated to shorter OS with the highest accuracy (C-index, 0.656; hazard ratio, 7.042; 95% confidence interval, 2.0–25.0; p = 0.002). Conclusion: A low LMR may identify patients who would be candidate for NIVO + IPI therapy for mRCC. [ABSTRACT FROM AUTHOR]

Objectives: Immune checkpoint inhibitors and enfortumab vedotin have opened new avenues for sequential treatment strategies for locally advanced/metastatic urothelial carcinoma (la/mUC). In the pre‐enfortumab vedotin era, many patients could not receive third‐line treatment owing to rapid disease progression and poor general status. This study aimed to analyze real‐world sequential treatment practices for la/mUC in Japan, with a focus on patients who do not receive third‐line treatment. Methods: We analyzed data for 1023 la/mUC patients diagnosed between January 2020 and December 2021 at 54 institutions from a Japanese nationwide cohort. Results: At the median follow‐up of 28.5 months, the median overall survival from first‐line initiation for 905 patients who received systemic anticancer treatment was 19.1 months. Among them, 81% and 32% received second‐ and third‐line treatment. Notably, 52% had their treatment terminated before the opportunity for third‐line treatment. Multivariate logistic regression analysis revealed that low performance status (≥1), elevated neutrophil‐to‐lymphocyte ratio (≥3), and low body mass index (<21 kg/m2) at the start of first‐line treatment were independent risk factors for not proceeding to third‐line treatment (p = 0.0024, 0.0069, and 0.0058, respectively). In this cohort, 33% had one of these factors, 36% had two, and 15% had all three. Conclusions: This study highlights the high frequency of factors associated with poor tolerance to anticancer treatment in la/mUC patients. The findings suggest the need to establish optimal sequential treatment strategies, maximizing efficacy within time and tolerance constraints, while concurrently providing strong supportive care, considering immunological and nutritional aspects. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we evaluated whether SARS‐CoV‐2 mRNA vaccines induce anti‐human leukocyte antigen (HLA) antibodies and anti‐ ABO blood type antibodies (ABOAb) in kidney transplant recipients (KTRs). Methods: Sixty‐three adult KTRs with functioning grafts who received two doses of the SARS‐CoV‐2 mRNA vaccine were enrolled in this cohort. Changes in anti‐ABO blood type immunoglobulin IgM and IgG antibody titers, flow panel reactive antibody (PRA), de novo donor‐specific anti‐human leukocyte antigen antibodies (DSA), and kidney allograft function before and after vaccination were evaluated. Results: Only one patient experienced conversion from negative to positive flow PRA after vaccination. However, there was no DSA in single antigen flow‐bead assays. The mean fluorescence intensity (MFI) in the eight DSA‐positive recipients did not significantly change before and after vaccination (p =.383), and no additional DSA was produced after vaccination in those patients. No significant elevation of ABOAb titer was observed for either IgM (p =.438) or IgG (p =.526) after vaccination. There was no significant deterioration in estimated glomerular filtration rate (eGFR) after vaccination (p =.877) or elevation of the urine protein‐to‐creatinine ratio (p =.209) after vaccination. One episode of AMR was observed in addition to a preexisting acute cellular rejection. Conclusions: The SARS‐CoV‐2 mRNA vaccine did not induce anti‐HLA antibody or ABOAb production in KTRs. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated whether the treatment history of low‐dose rituximab affected safety profiles, and humoral and cellular responses induced by severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid vaccine in healthy controls and kidney transplant recipients. Methods: We enrolled 10 healthcare workers as controls, 22 kidney transplant recipients with rituximab, and 36 kidney transplant recipients without rituximab without history of coronavirus disease 2019 who received two doses of vaccine. We assessed anti‐severe acute respiratory syndrome coronavirus 2 spike antibody and the antigen‐specific T cells using enzyme‐linked immunospot against spike protein at baseline and after two doses of vaccine. Results: All controls showed anti‐severe acute respiratory syndrome coronavirus 2 antibody seroconversion and enzyme‐linked immunospot positivity. Only 19/58 (33%) kidney transplant recipients experienced anti‐severe acute respiratory syndrome coronavirus 2 antibody seroconversion and 31/58 (53%) kidney transplant recipients developed enzyme‐linked immunospot assay positivity after vaccination. The anti‐severe acute respiratory syndrome coronavirus 2 antibody seroconversion rate and enzyme‐linked immunospot assay positivity rate after vaccination were not significantly different between kidney transplant recipients with or without rituximab. Multivariate regression analysis demonstrated rituximab was not associated with a lack of humoral and cellular responses to the vaccine. Conclusions: Low‐dose rituximab in kidney transplant recipients did not affect humoral or cellular responses to the severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid vaccine without severe systemic adverse events including the deterioration of kidney function. [ABSTRACT FROM AUTHOR]

Objectives: To assess the impact of histological variants on survival and response to treatment with pembrolizumab in patients with chemo‐resistant urothelial carcinoma (UC). Patients and Methods: The medical records of 755 patients with advanced UC who received pembrolizumab were reviewed retrospectively. Patients were classified into pure UC (PUC) and each variant. Best overall response (BOR) and overall survival (OS) were compared between the groups using a propensity score matching (PSM). Results: Overall, 147 (19.5%) patients harboured any histological variant UC (VUC). After PSM, there were no significant differences in the objective response rate (ORR, 24.5% vs 17.3%, P = 0.098) or disease control rate (DCR, 36.7% vs 30.2%, P = 0.195) when comparing patients with any VUC and PUC. Furthermore, any VUC, as compared with PUC, was associated with a similar risk of death (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.68–1.20; P = 0.482). Squamous VUC, which was the most frequent variant in the cohort, had a comparable ORR, DCR and OS as compared with PUC or non‐squamous VUC. The patients with sarcomatoid VUC (n = 19) had significantly better ORR (36.8%, P = 0.031), DCR (52.6%, P = 0.032), and OS (HR 0.37, 95% CI 0.15–0.90; P = 0.023) compared to patients with PUC. Conclusions: The presence of variant histology did not seem to affect BOR or OS after pembrolizumab administration in patients with chemo‐resistant UC. The patients with sarcomatoid VUC achieved favourable responses and survival rates compared to PUC. [ABSTRACT FROM AUTHOR]

• We evaluated the outcomes of 4 kidney transplant recipients with mitochondrial disease. • None of the recipients experienced rejection. • The grafted kidney of the patient who received it from her mother lost function at 5 years post-transplantation due to focal segmental glomerular sclerosis. • A patient with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes died 2 years after transplantation due to encephalopathy progression with stable kidney function. Mitochondrial disease can affect many organs, including the brain, nerves, heart, liver, eyes, ears, pancreas, and kidneys. Kidney transplantation is a treatment option for renal failure due to mitochondrial disease; however, the prognosis of patients who undergo kidney transplantation for mitochondrial disease is unknown. Here we evaluated the outcomes of kidney transplant recipients with mitochondrial disease. Clinical data were obtained from 4 kidney transplantation recipients who were followed at our department. Of the 4 transplantations, 3 were performed in our department: 2 patients received kidneys from their fathers, and a third from his wife. The fourth recipient received a kidney from her mother—who had a mitochondrial genetic abnormality—at another hospital. Of the 4 recipients, 3 were diagnosed with mitochondrial disease before the transplantation, and the fourth was diagnosed after. All recipients had sensorineural deafness and diabetes mellitus, and only 1 had a history of encephalopathy and stroke-like episodes before the transplantation. One patient died 2 years after transplantation due to encephalopathy progression with stable kidney function. The grafted kidney of the patient who received it from her mother lost function at 5 years post-transplantation. A graft biopsy revealed focal segmental glomerular sclerosis due to mitochondrial disease. The other patients' kidney functions remained stable. None of the recipients experienced rejection. In kidney transplantation for mitochondrial disease, attention should be paid to the exacerbation of comorbidities, while careful consideration should be given to donors with a mitochondrial genetic abnormality. [ABSTRACT FROM AUTHOR]