Importance of Management of Lifestyle-Related Diseases After Kidney Donation to Living Donors.

BACKGROUND: Living kidney transplant donors are classified as stage 3 chronic kidney disease after kidney donation. For this reason, we provide daily lifestyle guidance, such as blood pressure and weight management before surgery, and dietary counseling focused on salt restriction. We emphasize providing lifestyle guidance after kidney donation. METHOD: At Osaka Medical and Pharmaceutical University Hospital, living kidney donors are scheduled for their first postoperative visit 1 month after kidney donation, followed by regular checkups every 6 months after that, starting 3 months after the initial visit. When living kidney donors come to the Renal Replacement Therapy Selection Outpatient Clinic before kidney transplantation, we provide sufficient explanations of the potential risks that may arise after kidney donation and ensure that they understand the importance of regular postoperative checkups. Apart from cases where patients reside far away, and we ask another hospital to provide postoperative follow-up, we can achieve regular checkups for almost all cases. RESULTS: Eighty-four living kidney transplant donors are being followed up at Osaka Medical and Pharmaceutical University Hospital. The average age is 59.8 ± 11.8 years, showing a trend of aging. Among the donors under follow-up, 7 developed hyperlipidemia, 2 developed hypertension, and 1 developed diabetes as new-onset lifestyle diseases after kidney donation. CONCLUSION: The ability to empathize with and support the anxieties associated with kidney donation and build a strong relationship of trust with the donors has become a significant factor in achieving a high rate of regular checkups after kidney donation. As a result, it has led to early detection and intervention for donor diseases, contributing to the maintenance of their health. Managing lifestyle-related diseases after kidney donation is essential for living kidney donors.

Nephron-sparing ureteroscopic surgery vs. radical nephroureterectomy: comparable survival-outcomes in upper tract urothelial carcinoma.

PURPOSE: This study investigates the utility of ureteroscopic surgery (URS) as an alternative to radical nephroureterectomy (RNU) in managing upper tract urothelial carcinoma (UTUC), with a focus on survival outcomes and re-evaluation of current the European Association of Urology guidelines criteria. METHODS: We conducted a retrospective, multi-institutional review of 143 UTUC patients treated with URS (n = 35) or RNU (n = 108). Clinicopathological factors were analyzed, and survival outcomes were assessed using Kaplan-Meier analysis and Cox proportional-hazards models. RESULTS: The median follow-up period was 27 months. Overall survival (OS) and radiographic progression-free survival (rPFS) were comparable between the URS and RNU groups (OS: HR 2.42, 95% CI 0.63-9.28, P = 0.0579; rPFS: HR 1.82, 95% CI 0.60-5.47, P = 0.1641). URS conferred superior renal function preservation. In patients characterized by factors such as radiographically invisible lesions, negative cytology, pTa stage, low-grade tumors, and multiple lesions, the OS outcomes with URS were comparable to those with RNU as follows: radiographically invisible lesions (P = 0.5768), negative cytology (P = 0.7626), pTa stage (P = 0.6694), low-grade tumors (P = 0.9870), and multiple lesions (P = 0.8586). CONCLUSION: URS offers survival outcomes similar to RNU, along with better renal function preservation, especially in low-risk UTUC patients. These findings underscore the urgency of re-evaluating the current EAU guidelines and encourage further research into determining the ideal patient selection for URS in UTUC treatment.

Usefulness of Dietary Salt Restriction in Kidney Transplant Recipients: Analysis of Blood Pressure Levels Depending on the Differences in the Levels of Salt Intake.

BACKGROUND: Sodium retention causes post-transplant hypertension, and sodium restriction is recommended in kidney transplantation recipients. We investigated the changes in salt intake and age-specific differences in salt intake over the post-transplant periods and considered what guidance is important for salt reduction tailored to individual recipients. METHODS: We calculated salt intake for 38 recipients who underwent kidney transplantation from August 2013 to August 2018 using Tanaka's equation and extracted their blood pressure (BP) levels. RESULTS: The rate of achieving the desired level of salt intake (<6 g/d) was 7.9%. The average salt intake was 7.8 ± 1.4 g. Average BP by salt intake was as follows: <6 g/d, 109/71 mm Hg; 6 to <7 g/d, 127/84 mm Hg; 7 to <8 g/d, 124/79 mm Hg, 8 to <9 g/d, 130/73 mm Hg; 9 to <10 g/d, 133/83 mm Hg; and >10g/d, 137/81 mm Hg. DISCUSSION: Awareness of the need for salt restriction diminishes as time passes after transplantations, leading to increased salt uptake; therefore, regular guidance for keeping salt intake low is necessary for patients to maintain the awareness of salt restriction. The recipients with higher salt intake had higher blood pressure, suggesting the need for managing salt reduction. CONCLUSIONS: Dietary counseling showed a short-term efficacy for reducing sodium intake and clinically relevant BP improvement in renal allograft recipients.

Unplanned hemodialysis initiation and low geriatric nutritional risk index scores are associated with end-stage renal disease outcomes.

Patients with end-stage renal disease (ESRD) have a low nutritional status and a high mortality risk. The geriatric nutritional risk index (GNRI) is a predictive marker of malnutrition. However, the association between unplanned hemodialysis (HD) and GNRI with mortality remains unclear. In total, 162 patients underwent HD at our hospital. They were divided into two groups: those with unplanned initiation with a central venous catheter (CVC; n = 62) and those with planned initiation with prepared vascular access (n = 100). There were no significant differences in sex, age, malignant tumor, hypertension, and vascular disease, while there were significant differences in the times from the first visit to HD initiation (zero vs. six times, p < 0.001) and days between the first visit and HD initiation (5 vs. 175 days, p < 0.001). The CVC insertion group had significantly lower GNRI scores at initiation (85.7 vs. 99.0, p < 0.001). The adjusted hazard ratios were 4.002 and 3.018 for the GNRI scores and frequency, respectively. The 3-year survival rate was significantly lower in the CVC + low GNRI group (p < 0.0001). The GNRI after 1 month was significantly inferior in the CVC insertion group. Inadequate general management due to late referral to the nephrology department is a risk factor for patients with ESRD.

Increased BUB1B/BUBR1 expression contributes to aberrant DNA repair activity leading to resistance to DNA-damaging agents.

There has been accumulating evidence for the clinical benefit of chemoradiation therapy (CRT), whereas mechanisms in CRT-recurrent clones derived from the primary tumor are still elusive. Herein, we identified an aberrant BUB1B/BUBR1 expression in CRT-recurrent clones in bladder cancer (BC) by comprehensive proteomic analysis. CRT-recurrent BC cells exhibited a cell-cycle-independent upregulation of BUB1B/BUBR1 expression rendering an enhanced DNA repair activity in response to DNA double-strand breaks (DSBs). With DNA repair analyses employing the CRISPR/cas9 system, we revealed that cells with aberrant BUB1B/BUBR1 expression dominantly exploit mutagenic nonhomologous end joining (NHEJ). We further found that phosphorylated ATM interacts with BUB1B/BUBR1 after ionizing radiation (IR) treatment, and the resistance to DSBs by increased BUB1B/BUBR1 depends on the functional ATM. In vivo, tumor growth of CRT-resistant T24R cells was abrogated by ATM inhibition using AZD0156. A dataset analysis identified FOXM1 as a putative BUB1B/BUBR1-targeting transcription factor causing its increased expression. These data collectively suggest a redundant role of BUB1B/BUBR1 underlying mutagenic NHEJ in an ATM-dependent manner, aside from the canonical activity of BUB1B/BUBR1 on the G2/M checkpoint, and offer novel clues to overcome CRT resistance.

Risk Classification for Overall Survival by the Neutrophil-Lymphocyte Ratio and the Number of Metastatic Sites in Patients Treated with Pembrolizumab-A Multicenter Collaborative Study in Japan.

Pembrolizumab has emerged as the new standard of care in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas the optimal risk stratification to predict survival outcomes is still controversial. We examined a risk model for overall survival (OS) in mUC treated with pembrolizumab using our multi-institutional dataset (212 patients). The median age was 72 years old. Median OS from the initiation of pembrolizumab treatment was 11.7 months. The objective response rate (ORR) was 26.4%. On multivariate analysis, multiple metastatic sites and an NLR > 3.50 at the initiation of pembrolizumab treatment were identified as independent predictors for OS. We next developed a risk model using those two predictors. Patients without any factors were assigned to the favorable-risk group (26.5%). Patients with either factor and both factors were assigned to the intermediate-risk group (44.3%), and poor-risk group (29.2%), respectively. Kaplan-Meier curves showed clear discrimination of OS among the risk groups (p < 0.001). The ORR in each group was 35.7% in the favorable-risk group, 27.7% in the intermediate-risk group, and 17.7% in the poor-risk group. Given that the model can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice.

Distinct effect of body mass index by sex as a prognostic factor in localized renal cell carcinoma treated with nephrectomy ~ data from a multi-institutional study in Japan ~.

BACKGROUND: We assessed the prognostic value of body mass index (BMI) in Asian patients with localized RCC who underwent nephrectomy. METHODS: A total of 665 patients who underwent nephrectomy for localized RCC were enrolled in the present study and divided into the two BMI groups: i.e., BMI < 25 in 463 (69.6%) and BMI > 25 in 202 (30.4%) patients. RESULTS: In total, there were 482 (72.5%) males and 183 (27.5%) females. Five-year cancer-specific survival (CSS) rates were significantly higher in increased BMI than the lower BMI group (97.1 and 92.5%: P = 0.007). When stratified by sex, significantly longer CSS in higher BMI was confirmed in males (5-year CSS of 92.7% in BMI < 25 and 98.1% in BMI > 25, p = 0.005), while there was no difference in CSS between BMI groups for female patients. Multivariable analysis exhibited that higher BMI was an independent predictor for favorable CSS in male (cox model: p = 0.041, Fine & Gray regression model: p = 0.014), but not in the female. Subgroup analysis for CSS revealed that favorable CSS with higher BMI was observed in patient subgroups of age < 65 (p = 0.019), clear cell histology (p = 0.018), and tumor size > 4 cm, p = 0.020) as well as male (p = 0.020). CONCLUSION: Our findings collected from the multi-institutional Japanese dataset demonstrated longer survival in patients with higher BMI than lower BMI for non-metastatic RCC treated with nephrectomy. Intriguingly, this finding was restricted to males, but not to females.

Early Prostate-Specific Antigen (PSA) Change at Four Weeks of the First-Line Treatment Using Abiraterone and Enzalutamide Could Predict Early/Primary Resistance in Metastatic Castration-Resistant Prostate Cancer.

The identification of early or primary resistance to androgen signaling inhibitors (ASIs) is of great value for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the predictive value of prostate-specific antigen (PSA) response at dour weeks of first-line ASIs treatment for mCRPC patients. A total of 254 patients treated with ASIs (abiraterone acetate: AA and enzalutamide: Enz) at the first-line treatment are retrospectively analyzed. Patients are stratified according to the achievement of >30% PSA decline at 4 and 12 weeks from the treatment initiation. At four weeks of the treatment, 157 patients (61.8%) achieved >30% PSA decline from the baseline. Thereafter, 177 patients (69.7%) achieved >30% PSA decline at 12 weeks of the treatment. A multivariate analysis exhibits >30% PSA decline at four weeks as an independent predictor for overall survival (OS). We note that 30 of 97 (30.9%) patients who did not achieve >30% PSA decline at four weeks consequently achieved >30% PSA decline at 12 weeks, and had a comparable favorable three years OS rate as the 147 patients achieving >30% PSA decline at both 4 and 12 weeks. To identify the variables that discriminate the patient survival in 97 patients without achieving >30% PSA decline at four weeks, a multivariate analysis is performed. The duration of androgen deprivation therapy before CRPC ≤ 12 months and Eastern Cooperative Oncology Group Performance Status ≥ 1 are identified as independent predictors for shorter OS for those patients. These data offer a concept of early treatment switch after four weeks of first-line ASIs when not observing >30% PSA decline at four weeks-particularly in patients with a modest effect of ADT and poor performance status.

Risk stratification for the prediction of overall survival could assist treatment decision-making at diagnosis of castration-resistant prostate cancer: a multicentre collaborative study in Japan.

OBJECTIVES: To assess whether a new risk stratification system according to predictors for overall survival (OS) at the diagnosis of metastatic castration-resistant prostate cancer (mCRPC) could determine treatment outcomes and assist in treatment decision-making. PATIENTS AND METHODS: Two independent clinical cohorts of patients, treated with androgen signalling inhibitors (ASIs: abiraterone and enzalutamide) or docetaxel as a first-line treatment for mCRPC, were used in this study: a derivation cohort (196 patients with mCRPC) and an external validation cohort (211 patients with mCRPC). RESULTS: Three independent predictors for OS, including duration of initial androgen deprivation therapy <12 months before mCRPC diagnosis, alkaline phosphatase level >350 U/dL and haemoglobin level <11 g/dL at the diagnosis of mCRPC, were defined as risk factors. Patients with zero, one and multiple risk factors were assigned to a favourable-, intermediate- and poor-risk group, respectively. The median OS values in each risk group were well separated in the derivation cohort (P < 0.001) as well as in the validation cohort (P < 0.001). Of a total of 407 patients with mCRPC, 84 were assigned to the poor-risk group with the median OS of 12 months. In this group, a trend towards longer OS favouring docetaxel compared to ASIs as the first-line treatment (medians of 17 and 12 months, respectively) was observed. CONCLUSION: The new risk group stratification system could predict patient survival at the diagnosis of mCRPC. Given the convenience of these risk definitions, physicians may be encouraged to consider these risk groups in daily practice.

Effectiveness of Factor XIII Infusion in Treatment of Refractory Ureteral Leakage after Kidney Transplantation.

Despite the evolution of transplantation techniques, urological complications are common and result in loss of graft. We report the case of a 57-year-old man who developed continuous urine leakage despite pyeloureteral neoanastomosis and stenting after kidney transplantation from his dizygotic twin. Suspecting ureteral leakage, we performed pyeloureteral neoanastomosis using his native right ureter and a ureteral stent 5 days after the kidney transplant. However, urine leakage continued for several days. Because the plasma factor XIII level decreased to 48%, we administered factor XIII products (Fibrogammin P; CSL Behring, King of Prussia, PA) after the surgery. Although its utility and safety in patients with renal failure and/or transplantation are unclear, urine leakage stopped after the infusion of fibrogammin without any side effects. This is the first case report of the use of factor XIII for refractory urine leakage after kidney transplantation. Although further studies are needed, administration of factor XIII products could be one option for refractory urine leakage after transplantation.

Successful Treatment of Antibody-Mediated Rejection by De Novo Donor Specific Antibody After Primary Renal Transplantation in a Recipient From a Cadaveric Donor: A Case Report.

A 19-year-old Japanese male recipient, who received a living related kidney transplantation from his father at 5 years old, was hospitalized for second renal transplantation from a cadaveric donor. The recipient had had an antibody-mediated rejection (AMR) to the first transplanted kidney. HLA typing of A, B, and DRB showed 2 of 6 mismatches. Lymphocyte cytotoxicity test (LCT) and flow cytometry crossmatches (FCXM) were negative on T cells. Tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab induction were used as the standard immunosuppressive therapy. After second renal transplantation, his serum creatinine level favorably decreased until postoperative day (POD) 7, but his serum creatinine level raised from POD 8. We performed steroid pulse and intravenous immunoglobulin (IVIG). The episode biopsy showed AMR although FCXM and LCT were still negative on T cell. To determine the cause of AMR, we examined LABScreen single antigen test (One Lambda, Canoga Park, Calif., United States), and there was a donor-specific antibody (DSA) that is DQB8 in pre- and post-second renal transplantation. The DSA was suspected de novo DSA for the first transplanted kidney. AMR was successfully treated with plasma exchange, IVIG, and rituximab.

Adjuvant chemotherapy improves overall survival in patients with localized upper tract urothelial carcinoma harboring pathologic vascular invasion: a propensity score-matched analysis of multi-institutional cohort.

OBJECTIVE: Whether adjuvant chemotherapy (AC) for patients with upper tract urothelial carcinoma (UTUC) offers survival benefit is still controversial. To explore the impact of AC on overall survival (OS) of cN0M0 UTUC patients, we conducted a propensity score-matched analysis using the regression model, including pathologic features such as lymphatic and vascular invasion. METHODS: A multi-institutional cohort of 413 UTUC patient record was used. Propensity score matching was performed to reduce bias by potential confounding factors for survival, including pathologic features from the specimen of radical nephroureterectomy (RNU), RESULTS: Ninety-eight patients were identified as pair-matched groups (49 patients in RNU and 49 patients in RNU + AC). Kaplan-Meier curves demonstrated that a 5-year OS rate of 72.7% for patients treated with RNU + AC was significantly higher than 51.6% for those treated with RNU (p = 0.0156). On multivariate analysis, pathologic vascular invasion (HR 3.41, 95% CI 1.24-10.66, p = 0.0166) and administration of AC (HR 0.45, 95% CI 0.19-0.98, p = 0.0438) still remained as the significant predictors for OS. In patients with pathologic vascular invasion (51 of 98 patients), a significantly longer OS in RNU + AC groups was observed (median OS of 30 and 70 months in RNU and RNU + AC groups, respectively: p = 0.0432), whereas there was no significant difference in the OS between RNU (median OS: not reached) and RNU + AC (median OS: not reached) groups in patients without the invasion (p = 0.4549). CONCLUSION: The result indicates a significant benefit for OS by the administration of AC, and pathologic vascular invasion in the specimen of RNU could help the patient selection to better predict the effect of AC.

Prognostic impact of C-reactive protein-albumin ratio for the lethality in castration-resistant prostate cancer.

This study aimed to assess the clinical value of C-reactive protein-albumin ratio (CAR) at the initiation of first-line treatment for castration-resistant prostate cancer (CRPC). We identified 221 CRPC patients treated with either androgen-signaling inhibitors (ASIs: abiraterone and enzalutamide) or docetaxel as the first-line treatment. The value of CAR was evaluated at the initiation of first-line treatment. The optimal cutoff value of CAR for the prediction of lethality was defined by the receiver operating characteristic curve and the Youden Index. The primary endpoints of the study included overall survival (OS) and cancer-specific survival (CSS). The median age was 74 years. The optimal cutoff value of CAR in newly diagnosed CRPC patients was 0.5 (CAR > 0.5: n = 77 and CAR ≤ 0.5: n = 144). The 3-year OS and CSS rate in patients with CAR > 0.5 were significantly lower than those with CAR ≤ 0.5 (OS: 30.9% vs 55.5%, p < 0.001) (CSS: 42.5% vs 65.4%, p < 0.001). A multivariate analysis consistently demonstrated that CAR was an independent predictor for both OS and CSS. When stratified by the first-line treatments, patients with CAR > 0.5 has significantly shorter CSS than those with CAR ≤ 0.5 in abiraterone (median of 23 vs 49 months, p < 0.001) and enzalutamide (median of 23 vs 41 months, p = 0.0016), whereas no difference was observed in patients treated with docetaxel as the first-line treatment (median of 34 and 37 months, p = 0.7708). Despite the limited cohort size and retrospective design, increased CAR seemed to serve as an independent predictor of OS and CSS for patients newly diagnosed with CRPC.

Comparison of Radiographic Progression-Free Survival and PSA Response on Sequential Treatment Using Abiraterone and Enzalutamide for Newly Diagnosed Castration-Resistant Prostate Cancer: A Propensity Score Matched Analysis from Multicenter Cohort.

Background: There is emerging evidence that radiographic progression-free survival (rPFS) is highly correlated with overall survival (OS), potentially serving as an indicator of treatment outcome for castration-resistant prostate cancer (CRPC). The objective of this study is to assess rPFS and prostate specific antigen (PSA) response in sequential treatment using androgen signaling inhibitors (ASIs) including abiraterone and enzalutamide in newly diagnosed CRPC. Methods: Propensity score matching was performed to reduce bias by confounding factors between first-line ASIs. The primary endpoints of the study included rPFS, time to PSA progression (TTPP), and PSA response. Results: A paired-matched group of 184 patients were identified. From the initiation of first-line ASIs, there was no significant difference in rPFS, TTPP, and PSA response between treatment arms. From the initiation of second-line ASIs, enzalutamide following abiraterone consistently exhibited longer rPFS (median: 7 and 15 months, p = 0.04), TTPP, and better PSA response compared to the reverse, whereas OS did not reach significance (median: 14 and 23 months, p = 0.35). Conclusion: Although the effect of ASIs as the first line was similar, the extent of cross-resistance might differ towards less resistance in enzalutamide following abiraterone than the reverse.

The CANLPH Score, an Integrative Model of Systemic Inflammation and Nutrition Status (SINS), Predicts Clinical Outcomes After Surgery in Renal Cell Carcinoma: Data From a Multicenter Cohort in Japan.

BACKGROUND: A myriad of studies have demonstrated the clinical association of systemic inflammatory and nutrition status (SINS) including C-reactive protein/albumin ratio (CAR), the neutrophil/lymphocyte ratio (NLR), and the platelet/hemoglobin ratio (PHR). This study aimed to investigate the predictive value of the score integrating these variables (CANLPH) in patients with renal cell carcinoma (RCC). METHODS: Using cohort data from a multi-institutional study, 757 of 1109 patients were retrospectively analyzed. The optimal cutoff value for outcome prediction of continuous variables in CAR, NLR, and PHR was determined and the CANLPH score was then calculated as the sum score of 0 or 1 by the cutoff value in each ratio. RESULTS: The median follow-up time was 76 months for the patients who survived (n = 585) and 31 months for those who died (n = 172). The Youden Index offered an optimal cutoff of 1.5 for CAR and 2.8 for NLR, and a higher value from the cutoff was assigned as a score of 1. The cutoff value of the PHR was defined as 2.1 for males and 2.3 for females. The patients were assigned a CANLPH score of 0 (47.2%), 1 (31.3%), 2 (13.1%), or 3 (8.5%). In the multivariate analysis, the CANLPH score served as an independent predictor of cancer-specific mortality in both localized and metastatic RCC. CONCLUSION: The score was well-correlated with clinical outcome for the RCC patients. Because this score can be concisely measured at the point of diagnosis, physicians may be encouraged to incorporate this model into the treatment for RCC.

C-reactive protein-albumin ratio as a prognostic factor in renal cell carcinoma - A data from multi-institutional study in Japan.

INTRODUCTION: The C-reactive protein to albumin ratio (CAR) has been shown to provide prognostic information in several cancers. The objective in the study is to examine the prognostic value of CAR in patients with RCC who underwent nephrectomy. MATERIAL AND METHODS: The record data from multi-institutional study of 1,028 patients was analyzed in the study. The cut-off value of the CAR was defined by receive operating characteristic (ROC) analysis. Overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were evaluated, and univariate and multivariate analyses were conducted to assess the predictive value of the variables including CAR. RESULT: The optimal cut-off value of 0.073 in CAR was defined according to the ROC analysis. The AUC in CAR for CSS was greater than that of NLR and PLR, and that for RFS was also greater than GPS and mGPS. Multivariate analysis demonstrated that the CAR was an independent prognostic factor for OS (P < 0.001), CSS (P < 0.001) in total cohort and RFS (P = 0.029) in nonmetastatic cohort. CONCLUSION: The findings of the present study suggested that the preoperative CAR is an independent prognostic indicator of OS, CSS and RFS for patients with RCC. Since CAR can be assessed prior to surgery, clinicians should this take into account for the treatment decision making.

A Panel of MicroRNA Signature as a Tool for Predicting Survival of Patients with Urothelial Carcinoma of the Bladder.

INTRODUCTION AND OBJECTIVES: MicroRNA (miRNA) expression is altered in urologic malignancies, including urothelial carcinoma of the bladder (UCB). Individual miRNAs have been shown to modulate multiple signaling pathways that contribute to BC. To identify a panel of miRNA signature that can predict aggressive phenotype from normal nonaggressive counterpart using miRNA expression levels and to assess the prognostic value of this specific miRNA markers in patients with UCB. METHODS: To determine candidate miRNAs as prognostic biomarkers for dividing aggressive type of UCB, miRNA expression was profiled in patients' samples with an aggressive phenotype or nonaggressive phenotype using 3D-Gene miRNA labeling kit (Toray, Japan). To create a prognostic index model, we used the panel of 9-miRNA signature based on Cancer Genome Atlas (TCGA) data portal (TCGA Data Portal (https://tcgadata.nci.nih.gov/tcga/tcgaHome2.jsp)). miRNA expression data and corresponding clinical data, including outcome and staging information of 84 UCB patients, were obtained. The Kaplan-Meier and log-rank test were performed to quantify the survival functions in two groups. RESULTS: Deregulation of nine miRNAs (hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-145-5p, hsa-miR-4324, hsa-miR-34b-5p, hsa-miR-29c-3p, hsa-miR-135a-3p, and hsa-miR-33b-3p) was determined in UCB patients with aggressive phenotype compared with nonaggressive subject. To validate the prognostic power of the nine-signature miRNAs using the TCGA dataset of bladder cancer, the survival status and tumor miRNA expression of all 84 TCGA UCB patients were ranked according to the prognostic score values. Of nine miRNAs, six were associated with high risk (hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-4324, hsa-miR-34b-5p, and hsa-miR-135a-3p) and three were shown to be protective (hsa-miR-145-5p, hsa-miR-29c-3p, and hsa-miR-33b-3p). Patients with the high-risk miRNA signature exhibited poorer OS than patients expressing the low-risk miRNA profile (HR = 7.05, p < 0.001). CONCLUSIONS: The miRNA array identified nine dysregulated miRNAs from clinical samples. This panel of nine-miRNA signature provides predictive and prognostic value of patients with UCB.

Preoperative Measurement of the Modified Glasgow Prognostic Score Predicts Patient Survival in Non-Metastatic Renal Cell Carcinoma Prior to Nephrectomy.

PURPOSE: The modified Glasgow Prognostic Score (mGPS) by measurement of serum C-reactive protein and albumin levels has been shown to provide prognostic value in various cancer types. The purpose of this study was to evaluate whether preoperative assessment of the mGPS predicts patient survival outcome in renal cell carcinoma (RCC). MATERIALS AND METHODS: Clinicopathological and follow-up data in 219 RCC patients, all of whom underwent curative or non-curative nephrectomy, were collected. Overall survival (OS) and cancer-specific survival (CSS) after nephrectomy were evaluated, and univariate and multivariate analyses were conducted to assess the predictive value of the variables, including the mGPS. RESULTS: During the median follow-up of 57 months, 53 patients (24.2%) were deceased within 22 months of the median OS. The 5-year OS rate from nephrectomy was 85.9 and 18.8% in non-metastatic (n = 195) and metastatic (n = 24) patients, respectively. Increasing mGPS was associated with shorter OS in non-metastatic patients (2-year OS rate of 98.2% in mGPS0, 73.3% in mGPS1, and 44.4% in mGPS2; hazard ratio [HR] 9.96, 95% confidence interval [CI] 4.88-20.13, p < 0.001), whereas no significant difference in OS according to the mGPS was seen in metastatic patients (HR 2.01, 95% CI 0.79-5.16, p = 0.137). On multivariate analysis, the mGPS remained as an independent predictor for OS (HR 5.24, 95% CI 1.39-19.77, p = 0.015) and CSS (HR 4.69, 95% CI 1.13-20.96, p = 0.034) in non-metastatic RCC patients. CONCLUSIONS: The mGPS appeared to be a reliable, preoperatively defined predictive marker with widely standardized protocol in non-metastatic RCC, and should therefore be considered in treatment decision making for RCC patients.

Remarkable response to fluorouracil, leucovorin, oxaliplatin, and irinotecan therapy in urothelial cancer of the renal pelvis: a case report.

BACKGROUND: No standard chemotherapy regimen for advanced urothelial cancer has been established, except for cisplatin-based regimens. We report the case of a patient with double primary cancer, urothelial carcinoma of the upper urinary tract and colorectal cancer, who underwent oxaliplatin-based chemotherapies. CASE PRESENTATION: A 56-year-old Japanese man presented to our hospital with the diagnosis of a left renal pelvic tumor and rectal cancer. Several examinations including ureteroscopic biopsy and computed tomography-guided biopsy were performed; however, the diagnosis of renal pelvic cancer could not be made. Because the rectal cancer had been growing during the course of examination, he underwent five cycles of neoadjuvant chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan. The volumes of both the rectal cancer and renal pelvic tumor drastically decreased. He then underwent pelvic evisceration with colostomy and ureterocutaneostomy. The histological diagnosis of the renal pelvic tumor was urothelial carcinoma. He is free of disease at 12 months after the treatment. CONCLUSIONS: To the best of our knowledge, this is the first report describing a remarkable response to fluorouracil, leucovorin, oxaliplatin, and irinotecan therapy for renal pelvic cancer. We suggest fluorouracil, leucovorin, oxaliplatin, and irinotecan is an effective therapy for patients with advanced urothelial cancer.

The combination of preoperative platelet count and neutrophil lymphocyte ratio as a prognostic indicator in localized renal cell carcinoma.

INTRODUCTION: The combination of platelet count and neutrophil to lymphocyte ratio (COP-NLR) has been shown to provide prognostic information in several cancers, whereas its prognostic value in renal cell carcinoma (RCC) has not been reported. The objective of the present study was to examine the preoperative prognostic value of the COP-NLR in patients with localized RCC undergoing nephrectomy. MATERIAL AND METHODS: The record of 268 patients, who underwent nephrectomy due to a diagnosis of RCC at our institute was analyzed in the study. The cut-off value of platelet count and NLR were defined by receive operating characteristic (ROC) analysis and the areas under the curve (AUC). Patients with both an increased platelet count (> 310×109/l) and an elevated NLR (> 3.85) were assigned to the score 2, and patients with one or neither of these indicators were assigned to the score 1 or 0, respectively. The impact of the COP-NLR and other clinicopathological characteristics on overall survival (OS) and recurrence-free survival (RFS) were evaluated using the univariate and multivariate Cox regression analysis. RESULT: The median follow-up duration after surgical resection was 60 months. Multivariate analysis using the 10 clinicopathological findings selected by univariate analyses demonstrated that the preoperative COP-NLR was an independent prognostic factor for OS (HR: 2.32, 95%CI: 1.22 to 4.26, p=0.011) and RFS (HR: 1.91, 95%CI: 1.02 to 3.53, p=0.044). CONCLUSION: The findings of the current study suggested that the preoperative COP-NLR is an independent prognostic indicator of OS and RFS for patients with localized RCC.