Experience and prognostic analysis with avelumab switch maintenance treatment in metastatic urothelial carcinoma.

INTRODUCTION: Avelumab is approved for metastatic urothelial carcinoma (mUC) maintenance therapy and prolongs overall survival (OS). We explored trends related to avelumab treatment of mUC patients. METHODS: A total of 72 patients with mUC treated with first-line chemotherapy, from January 2019 to November 2022, at our affiliated institutions, were analyzed. We compared clinical parameters and the prognosis of patients treated with avelumab (Ave; n=43), because of progression during first-line chemotherapy, with untreated patients (Ave-untreated; n=29). Among the Ave-treated group, we classified patients showing a complete or partial response or stable disease in their best response to avelumab maintenance therapy as avelumab (Ave)-suitable patients; these were retrospectively analyzed. Potential prognostic factors, including the geriatric nutritional risk index (GNRI) for determining patients suitable for Ave, were evaluated. RESULTS: The basic clinical parameters of patients when first-line treatment was initiated were not statistically different between the two groups. The Ave-suitable group (median 26.6 months, 95% confidence interval [CI]: 19.4-not reached [NR]) showed significantly longer median OS after first-line treatment than the Ave-untreated group (median 12.0 months, 95% CI: 7.5-NR) with tolerable adverse events. The cut-off values of prognostic factors were set by receiver operating characteristic curve. Low age and GNRI sustainability revealed as significant prognostic factors for being Ave-suitable both in univariate and multivariate analysis. CONCLUSION: In mUC, avelumab maintenance prolonged OS within tolerable safety profiles. GNRI sustainability may be used as biomarker to predict being Ave-suitable.

Three-dimensional computed tomography-based resection process map for robot-assisted partial nephrectomy: propensity score matching of a single-center retrospective study.

BACKGROUND AND OBJECTIVES: We aimed to examine the effect of preoperative three-dimensional (3D) computed tomography (CT)-based resection process map (RPM) imaging on the outcomes of robot-assisted partial nephrectomy (RAPN). METHODS: We retrospectively analyzed 177 patients (RPM group, n = 92; non-RPM group, n = 85) who underwent this surgery between November 2012 and April 2022. Patient-specific contrast-enhanced CT images were used to construct an RPM, a 3D representation of the kidney showing the planned tumor resection and a 5 mm safety margin. Outcome analyses were performed using propensity score matching. The primary endpoint was the trifecta achievement rate. RESULTS: We extracted 90 cases. The trifecta achievement rate showed no significant differences between the RPM (73.3%) and non-RPM groups (73.3%). However, the RPM group had fewer Grade 3 and higher complications (0.0% vs. 13.3%, p = 0.026). The da Vinci Xi (OR 3.38, p = 0.016) and tumor diameter (OR 0.95, p = 0.013) were independent factors affecting trifecta achievement in multivariate analysis. Using RPM imaging was associated with the absence of Grade 3 and higher perioperative complications (OR 5.33, p = 0.036) in univariate analysis. CONCLUSIONS: Using preoperative 3D CT-based RPM images before RAPN may not affect trifecta achievement, but may reduce serious complication occurrence by providing detailed information on tumor resection.

GNRI Sustainability during One Cycle of First-Line Chemotherapy as a Prognostic Indicator in Patients with Metastatic Urothelial Carcinoma.

INTRODUCTION: This study evaluated the prognostic value of a sustained high Geriatric Nutritional Risk Index (GNRI) during first-line chemotherapy for patients with metastatic urothelial carcinoma (mUC). METHODS: Between January 2018 and February 2022, 123 patients received platinum-based chemotherapy at Nagoya City University Hospital and affiliated institutions. Of these, 118 eligible patients who showed an Eastern Cooperative Oncology Group performance status (ECOG-PS) between 0 and 2 were retrospectively examined. Based on body mass index and serum albumin levels, GNRI was calculated immediately before and after the first primary chemotherapy cycle. Patients were divided into two groups based on GNRI: GNRI sustained ≥92 in sustainable (n = 63) and GNRI <92 in unsustainable (n = 55) groups, respectively. Clinical outcomes were compared. RESULTS: No significant differences were noted between the two groups for age, gender, cycle of first-line treatment, and type of series of sequential treatments after failure of first-line therapy. Median overall survival from the start of first-line chemotherapy was 30.2 months (95% confidence interval [CI]: 20.9-NA) for sustainable and 12.6 months (95% CI: 9.0-21.2) for unsustainable groups, respectively (p < 0.05). Multivariate analysis identified ECOG-PS:2 and fatigue, an adverse event, as independent predictors of unsustainable GNRI transition (95% CI: 1.29-90.6, odds ratio [OR]: 10.8; 95% CI: 1.06-26.9, OR: 5.34, respectively). CONCLUSION: Sustaining a high level of GNRI was an important prognostic indicator in patients with mUC receiving first-line chemotherapy. Appropriate intervention for controlling adverse events, including fatigue, may enhance physical strength during cancer treatment.

Clinical characteristics of Raoultella ornithinolytica bacteremia and antimicrobial susceptibility of Raoultellaornithinolytica.

Raoultella ornithinolytica (R. ornithinolytica) is a gram-negative rod that was considered related to Klebsiella oxytoca and was classified as R. ornithinolytica in 2001. R. ornithinolytica is known as a histamine-producing bacterium that causes mackerel poisoning. Although only few clinical cases of R. ornithinolytica infection in humans have been reported, the number of diagnosed cases is expected to increase owing to the advancements in identification methods. In the present study, we performed a retrospective analysis of cases of R. ornithinolytica infection detected at our hospital. From September 2019 to July 2021, 62 specimens positive for R. ornithinolytica were obtained after removing duplicates. The clinical courses of these cases were investigated retrospectively based on electronic medical records. Of the 62 specimens, 24 were sputum, 19 were urine, three were stool, six were blood, four were bile, and six were other specimens. All the six blood culture specimens in which R. ornithinolytica was detected were from male patients, and the causative diseases were cholangitis in four cases and complicated pyelonephritis in two cases. Of these, two patients with cholangitis succumbed to death due to the worsening of underlying cancer. Identification of R. ornithinolytica is reportedly difficult, and some instruments may misidentify it as Klebsiella oxytoca. The prognosis of R. ornithinolytica infection has been reported to be good when susceptible drugs are used. However, high mortality rates were also reported despite the use of these drugs, suggesting the need for further investigation of clinical features of R. ornithinolytica infection.

Elevated eosinophils proportion as predictor of immune-related adverse events after ipilimumab and nivolumab treatment of advanced and metastatic renal cell carcinoma.

OBJECTIVES: Ipilimumab and nivolumab treatment against advanced and metastatic renal cell carcinoma (RCC) causes severe and lethal immune-related adverse events (irAEs). Predicting irAEs might improve clinical outcomes, however no practical biomarkers exist. This study examined whether eosinophils could be effective biomarkers for ≥grade 2 irAEs in RCC. METHODS: We retrospectively analyzed 75 patients with RCC treated with ipilimumab and nivolumab between August 2018 and March 2021 in a multicenter study. Eosinophils were examined before and 2 weeks after treatment, and immediately after irAEs development. The optimal cut-off value for ≥grade 2 irAEs was determined by a receiver operating characteristic (ROC) curve. Univariate and multivariate analyses were undertaken to identify predictors of ≥grade 2 irAEs. RESULTS: Two weeks after treatment, eosinophils were significantly upregulated in patients who had experienced ≥grade 2 irAEs than in those who had not experienced irAEs (mean, 5.7% vs. 3.2%; p < 0.05). The optimal cut-off value for eosinophils against ≥grade 2 irAEs was 3.0% (area under the curve = 0.69). In multivariate analyses, an eosinophil level ≥ 3.0% was a risk factor for ≥grade 2 irAEs (odds ratio 4.18, 95% confidence interval 1.16-15.1). The eosinophil level 2 weeks after treatment was upregulated by the onset of any type of irAEs including endocrine, gastrointestinal, pulmonary and skin disorders. CONCLUSIONS: An increased eosinophil level 2 weeks after treatment might be an effective biomarker for ≥grade 2 irAEs in patients with RCC treated with ipilimumab and nivolumab.

Hemoglobin and neutrophil levels stratified according to International Metastatic Renal Cell Carcinoma Database Consortium risk predict the effectiveness of ipilimumab plus nivolumab in patients with advanced metastatic renal cell carcinoma.

OBJECTIVE: To identify biomarkers associated with the effectiveness of ipilimumab plus nivolumab against advanced metastatic renal cell carcinoma. METHODS: We retrospectively analyzed the data of 75 patients treated with ipilimumab plus nivolumab at seven hospitals between August 2018 and April 2021. Prognostic biomarkers were assessed prior to initiating treatment with ipilimumab plus nivolumab. Median overall survival and progression-free survival were examined using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify predictors of disease progression. The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors most important for predicting disease progression were determined using classification and regression tree analysis. RESULTS: Median overall survival and progression-free survival were longer in the intermediate IMDC risk group than in the poor IMDC risk group (overall: not reached vs. 18.3 months; progression-free: not reached vs. 13.5 months). The multivariate analysis identified poor IMDC risk as a risk factor for disease progression (hazard ratio 2.61, 95% confidence interval: 1.05-6.51). Based on the results of the classification and regression tree analysis, the cohort was divided into non-anemia, anemia + neutro-Low, and anemia + neutro-High groups. Median overall survival and progression-free survival were longer in the non-anemia and anemia + neutro-Low groups than in the anemia + neutro-High group (overall: not reached vs. 29.3 months vs. 4.3 months: progression-free: not reached vs. 29.0 months vs. 3.9 months). CONCLUSION: Hemoglobin and neutrophil levels may represent crucial biomarkers for predicting the effectiveness of ipilimumab plus nivolumab therapy in patients with renal cell carcinoma.

Survival Outcome after Reduced-Port Laparoscopic Radical Cystectomy for Bladder Cancer: Long-Term Follow-Up Analysis.

INTRODUCTION: This study had two objectives: (i) to evaluate oncological outcomes in a long-term follow-up of patients with bladder cancer after reduced-port laparoscopic radical cystectomy (RP-LRC) and (ii) to assess the effect of modified Glasgow prognostic scores (mGPS) on patient outcomes. METHODS: Consecutive patients (n = 100) who received RP-LRC between March 2012 and December 2018 at our institution and affiliated hospital were retrospectively reviewed. Preoperative serum albumin and C-reactive protein levels were determined. Patients were grouped based on clinical T stage (≤cT2: n = 75, ≥cT3: n = 25) using pooled cumulative data. Oncological outcomes and mGPS as a prognostic biomarker were analyzed retrospectively. Kaplan-Meier curves displayed recurrence and survival rates. Univariate and multivariate Cox regression analyses evaluated potential prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS). RESULTS: Patient characteristics between the two groups were statistically similar for preoperative hematological and mGPS status, blood loss level, rate of allogeneic transfusion, and pneumoperitoneum time. After a median follow-up period of 55 months, 40/100 patients experienced disease relapse. RFS and CSS for ≤cT2 were significantly less than for ≥cT3 (p < 0.001, p < 0.05, respectively). Distant metastasis occurred in 30 patients with similar distributions of relapse sites between T-stage cohorts. Median RFS for mGPS 1/2 were 18.9 (95% confidence interval [CI]: 8.8-not assessed [NA]) and 35.0 (95% CI: 8.7-NA) months, respectively, significantly worse than for mGPS 0 (median NA, 95% CI: NA-NA); CSS was similar. Univariate and multivariate analyses revealed ≥cT3 stage, worse clinical N stage, and poor mGPS status were significant prognostic factors for short RFS and CSS. CONCLUSIONS: A large proportion of bladder cancer patients who undergo RP-LRC experience relapse, with ≥cT3 stage, worse clinical N stage or poor mGPS status identified as significant prognostic factors. Our findings may contribute to improved surgical procedures for such patients.

Comparison of drug susceptibility between Escherichia coli detected in stool cultures of patients undergoing transrectal prostate needle biopsy and Escherichia coli in hospital-wide urine antibiograms.

A prostate biopsy is essential for prostate cancer diagnosis. However, infections are one of the biopsy-associated complications, and post-biopsy fever is estimated to occur in approximately 1% of all cases. It may thus be beneficial to perform a rectal swab culture before a transrectal prostate biopsy to confirm the presence of resistant bacteria and select preventive antibacterial agents according to the drug susceptibility results. This study aimed to determine whether there is a difference between the drug susceptibility of bacteria detected in the stool of patients who were scheduled to undergo prostate biopsy and the hospital-wide urine antibiogram. Patients suspected of having prostate cancer who underwent transrectal prostate biopsy via transrectal ultrasonography between August 1, 2016, and June 30, 2020, were included in this study. Stool samples were collected and cultured before biopsy. Overall, 99 patients underwent prostate biopsy, and of these, culture results were available for 81 patients (81.8%). Escherichia coli was detected in 74.0% (60 samples) of the stool culture samples, of which 4 samples were extended-spectrum ß-lactamase-producing types. We found greater susceptibility of Escherichia coli to ampicillin, fluoroquinolones, sulfamethoxazole/trimethoprim, and cefixime in the stool culture antibiogram than in the hospital-wide urine antibiogram. We also found a significantly low incidence of ESBL-positive Escherichia coli in the stool culture antibiogram with p-values of 0.009, 0.007, and 0.03 compared to the hospital-wide urine antibiograms for 2017, 2018, and 2019, respectively. Stool culture of prostate cancer patients undergoing biopsy may provide useful information for selecting prophylactic antimicrobial agents.

Chronological transition in outcome of second-line treatment in patients with metastatic urothelial cancer after pembrolizumab approval: a multicenter retrospective analysis.

BACKGROUND: After first-line chemotherapy failure, metastatic urothelial carcinoma (mUC) patients undergo pembrolizumab (PEM) or gemcitabine and docetaxel (GD) therapy. We retrospectively investigated outcomes of second-line GD or PEM for mUC patients. METHODS: A total of 198 mUC patients from Nagoya City University and affiliated hospitals who received second-line treatment were grouped according to immune check point inhibitor (ICI) availability: Groups A (pre-ICI: n = 104) and B (post-ICI: n = 94). We compared clinical outcomes using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses assessed potential prognostic factors for overall survival (OS). RESULTS: Median OS was significantly longer for Group B [median 13.6 months, 95% confidence interval (CI): 7.6-17.6] than A (7.6 months, 5.3-8.8). By sub-group analysis, patients received no additional treatment (Naïve, n = 70), or PEM or GD (Salvage, n = 24) in Group B, with median OS of Naïve and A groups similar. Compared to the Salvage group, significant differences in OS were observed (median 7.6 months, 95% CI 5.3-8.8; Group A, 7.6 months, 4.7-13.8; Naïve, 25.7 months, 14.0-31.0; p < 0.01). For the Salvage group, OS for sequential treatment of GD-salvage PEM and PEM-salvage GD patients was similar (p = 0.10). Multivariate analysis showed a low neutrophil-to-lymphocyte ratio (NLR) and high geriatric nutritional risk index (GNRI) as significant prognostic factors affecting long OS [95% CI 1.12-3.45, hazard ratio (HR): 1.97; 95% CI 0.24-0.71, 0.41, respectively]. CONCLUSION: Second-line GD or PEM therapy for mUC patients showed equivalent survival benefits. GNRI and NLR are prognostic biomarkers for survival outcome.

Efficacy of fosfomycin in preventing infection after endoscopic combined intrarenal surgery in periods of limited supply of first- and second-generation cephalosporins.

OBJECTIVES: In March 2019, cefazolin was unavailable owing to difficulty in procuring the active ingredient. Furthermore, the supply of alternative drugs, such as cefotiam and cefmetazole, was limited. In the Department of Nephro-Urology, fosfomycin-based drugs are used as substitutes for cefazolin, which is a perioperative prophylactic antibacterial drug. Herein, we investigated the effectiveness of fosfomycin sodium and cefotiam in preventing infection after endoscopic combined intrarenal surgery as a retrospective preliminary study. METHODS: A total of 200 patients who underwent endoscopic combined intrarenal surgery at our department between August 2017 and January 2021 were included. The patients were administered cefotiam (n = 95) or fosfomycin (n = 105) as perioperative antibacterial agents. There were no significant differences in the median age or surgery time between the cefotiam and fosfomycin groups. Propensity score matching was performed to match the preoperative urine bacterial counts of both groups. Sixty-eight patients were selected from each group. RESULTS: The median postoperative hospital stay duration was 4 days for the two groups. The median maximum postoperative temperatures were 37.5 and 37.4°C, respectively. There were no significant differences between the maximum postoperative temperatures in both groups. Furthermore, there were no differences between the groups regarding the white blood cell counts, C-reactive protein levels, and aspartate aminotransferase and alanine aminotransferase levels postoperatively, as well as in terms of postoperative fever requiring additional antibiotics. CONCLUSIONS: During a period of difficulty in acquiring cefazolin and cefotiam, the use of fosfomycin allowed us to continue with the procedure without increased clinical complications.

First Report of Oncological Outcome and Prognostic Analysis in a First-Line Setting of Short Hydration Gemcitabine and Cisplatin Chemotherapy for Patients with Metastatic Urothelial Carcinoma.

OBJECTIVES: The aim of the study was to examine the effectiveness of a modified-short hydration gemcitabine and cisplatin (m-shGC) regimen for patients with metastatic urothelial carcinoma (mUC) and to assess the efficacy of a geriatric nutritional risk index (GNRI) with regard to prognosis. PATIENTS AND METHODS: From January 2016 to July 2020, 68 patients with mUC underwent first-line m-shGC therapy with 70 mg/m2 cisplatin and 1,000 mg/m2 gemcitabine (days 1, 8, and 15), with 2,050 mL fluid replaced on the first day of each 28-day cycle. Prior to the start of treatment, the serum neutrophil-to-lymphocyte ratio (NLR), and levels of albumin and C-reactive protein (CRP) in serum, as well as body heights and weights were measured. Patients were grouped according to GNRI <92 (low) or ≥92 (high). The analysis of data was done retrospectively. RESULTS: Median follow-up was found to be 12.9 (range 1.7-50.2) months and the objective response rate (ORR) was 54.4% after m-shGC treatment. The ORR was significantly different when high and low-GNRI groups were compared (ORR: 28.0 vs. 69.8% in low- vs. high-GNRI groups). Median overall survival (OS) was calculated as 8.6 (95% confidence interval [CI]: 5.4-21.3) and 34.5 (95% CI: 20.5-NA) months for low- and high-GNRI groups, respectively (p < 0.0001). Unlike for NLR and CRP, univariate and multivariate analyses revealed that low GNRI and visceral metastases were significant prognostic factors for short OS. CONCLUSIONS: First-line m-shGC showed a survival benefit for mUC, with GNRI a useful prognostic biomarker.

Efficacy of fosfomycin in the prevention of postoperative infection following transurethral resection of bladder tumor during periods of limited cefazolin, cefotiam, and cefmetazole supply.

INTRODUCTION: In March 2019, cefazolin availability was limited owing to the contamination of the drug substance. In addition, there was a difficulty in supplying drugs alternative to cefazolin, such as cefotiam and cefmetazole. In our Department of Nephro-urology, we used fosfomycin-based drugs to substitute cefazolin as perioperative preventive antibacterial drugs. In this study, we aimed to evaluate the usage status of perioperative prophylactic antibacterial drugs before and after the period of limited cefazolin supply and to investigate the efficacy and safety of fosfomycin sodium in preventing infections following transurethral resection of bladder tumor. METHODS: We enrolled 346 patients who underwent transurethral resection of bladder tumor in our department from April 2018 to August 2020. The patients received the following perioperative antibacterial agents: cefotiam (n = 146), fosfomycin (n = 166), and other antibacterial agents (n = 34). There was no significant difference in the median age or surgery time. RESULTS: The median length of hospital stay was 6, 5, and 5 days in the cefotiam, fosfomycin, and other antibacterial groups, respectively, with significant difference. The median maximum postoperative temperature was 37.1 °C in all groups, with no significant difference. There were no differences in C-reactive protein, aspartate aminotransferase, and alanine aminotransferase levels determined by postoperative blood tests; preoperative and postoperative urinary white blood cell counts; preoperative urine bacterial counts; and surgery-related infection requiring additional antibiotic treatments among the groups. CONCLUSIONS: The use of fosfomycin-based agents helped overcome the limited supply of cefazolin without worsening clinical outcomes.

Recruitment of miR-8080 by luteolin inhibits androgen receptor splice variant 7 expression in castration-resistant prostate cancer.

A need exists for seeking effective treatments for castration-resistant prostate cancer (CRPC) in response to its emergence following androgen deprivation therapy as a major clinical problem. In the present study, we investigated the chemopreventive and chemotherapeutic potential of luteolin, a flavonoid with antioxidative properties, on prostate cancer, including CRPC. Luteolin inhibited the progression of rat prostate carcinogenesis by induction of apoptosis in a transgenic rat for adenocarcinoma of prostate (TRAP) model. Luteolin decreased cell proliferation in a dose-dependent manner and induced apoptosis with the activation of caspases 3 and 7 in both rat (PCai1, established from a TRAP prostate tumor) and human (22Rv1) CRPC cells. Dietary luteolin also suppressed tumor growth via an increase in apoptosis and inhibition of angiogenesis in PCai1 and 22Rv1 xenografts implanted in castrated nude mice. We also focused on androgen receptor splice variant 7 (AR-V7), which contributes to cell proliferation and therapeutic resistance in CRPC. Luteolin dramatically suppressed AR-V7 protein expression in 22Rv1 cells in vitro and ex vivo. Microarray analysis identified MiR-8080, which contains a possible target sequence for AR-V7 3'-UTR, as a gene upregulated by luteolin. MiR-8080 transfection decreased the AR-V7 expression level and the induction of apoptosis in 22Rv1 cells. Furthermore, miR-8080 knockdown canceled luteolin decreasing AR-V7 and the cell growth of 22Rv1. MiR-8080 induced by luteolin intake enhanced the therapeutic effect of enzalutamide on 22Rv1 xenografts under castration conditions. These results indicate luteolin inhibits CRPC by AR-V7 suppression through miR-8080, highlighting luteolin and miR-8080 as promising therapeutic agents for this disease.

Luteolin suppresses bladder cancer growth via regulation of mechanistic target of rapamycin pathway.

Luteolin is a natural flavonoid with strong anti-oxidative properties that is reported to have an anti-cancer effect in several malignancies other than bladder cancer. In this study, we describe the effect of luteolin on a human bladder cancer cell line, T24, in the context of the regulation of p21, thioredoxin-1 (TRX1) and the mechanistic target of rapamycin (mTOR) pathway. Luteolin inhibited cell survival and induced G2/M cell-cycle arrest, p21 upregulation and downregulation of phospho(p)-S6, which is downstream of mTOR signaling. Luteolin also upregulated TRX1 and reduced intracellular reactive oxygen species production. In a subcutaneous xenograft mouse model using the rat bladder cancer cell line, BC31, tumor volumes were significantly decreased in mice orally administered luteolin compared to control. Immunohistochemical analysis revealed that increased p21 and decreased p-S6 expression were induced in the luteolin treatment group. Moreover, in another in vivo N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder cancer model, the oral administration of luteolin led to a trend of decreased bladder tumor dimension and significantly decreased the Ki67-labeling index and p-S6 expression. Furthermore, the major findings on the metabolism of luteolin suggest that both plasma and urine luteolin-3'-O-glucuronide concentrations are strongly associated with the inhibition of cell proliferation and mTOR signaling. Moreover, a significant decrease in the squamous differentiation of bladder cancer is attributed to plasma luteolin-3'-glucuronide concentration. In conclusion, luteolin, and in particular its metabolized product, may represent another natural product-derived therapeutic agent that acts against bladder cancer by upregulating p21 and inhibiting mTOR signaling.

Efficacy of a Newly Modified Short Hydration Method for Gemcitabine and Cisplatin Combination Chemotherapy in Patients with Urothelial Carcinoma.

INTRODUCTION: Conventional first-line chemotherapy for patients with metastatic urothelial carcinoma (UC) is gemcitabine and cisplatin (GC). However, cisplatin can cause renal failure, necessitating abundant fluid replacement and hospitalization during treatment. Recent evidence exists for short hydration methods in cisplatin-based chemotherapy. OBJECTIVE: This study aims to analyze the efficacy of newly established modified short hydration GC (m-shGC) therapy in patients with UC. METHODS: From May 2017 to March 2019, 48 patients with UC who received m-shGC therapy were treated with 1,000 mg/m2 gemcitabine on days 1, 8, and 15, and 70 mg/m2 cisplatin and 2,000 mL fluid replacement on day 1, in each 28-day cycle. We retrospectively evaluated renal function, serum electrolyte abnormalities, and adverse events (AEs) following treatment, and retrospectively compared patients under m-shGC therapy with those under conventional GC (c-GC) therapy from 2015 to 2017. In addition, from April 2019 to August 2019 in a prospective analysis, 15 patients were newly enrolled, and AE profiles and physical activity during m-shGC therapy were quantified using a wearable tracker. RESULTS: In a retrospective analysis of 101 patients (53 c-GC and 48 m-shGC), patient characteristics were not statistically significant between the two groups. Myelosuppression, including predominant neutropenia and decreased platelets, fatigue, nausea, and constipation were the main common AEs. However, renal function and serum sodium levels in the m-shGC group remained unchanged. Grade 3-4 AEs were not more severe in the m-shGC compared with the c-GC group. Furthermore, in a prospective analysis using a wearable tracker, the amount of walking by patients on day 1 significantly declined. However, immediate recovery occurred reflecting the short hydration. CONCLUSION: Our m-shGC therapy has an acceptable AE profile compared with conventional therapy, with UC patients showing good physical activity.

Low Geriatric Nutritional Risk Index as a Poor Prognostic Marker for Second-Line Pembrolizumab Treatment in Patients with Metastatic Urothelial Carcinoma: A Retrospective Multicenter Analysis.

BACKGROUND: We evaluated the prognostic efficacy of the Geriatric Nutritional Risk Index (GNRI) in second-line pembrolizumab (PEM) therapy for patients with metastatic urothelial carcinoma (mUC). PATIENTS AND METHODS: From January 2018 to October 2019, 52 mUC patients, treated previously with platinum-based chemotherapy, underwent second-line PEM therapy. Peripheral blood parameters were measured at the start of treatment: serum neutrophil-to-lymphocyte ratio (NLR), serum albumin, serum C-reactive protein (CRP), and body height and weight. PEM was intravenously administered (200 mg every 3 weeks). The patients were organized into two groups based on their GNRI (<92 [low GNRI] and ≥92 [high GNRI]), and the data were retrospectively analyzed. Adverse events (AEs) were evaluated and imaging studies assessed for all patients. Analyses of survival and recurrence were performed using Kaplan-Meier curves. Potential prognostic factors affecting cancer-specific survival (CSS) were assessed by univariate and multivariate Cox regression analyses. RESULTS: patients' baseline characteristics, except for their BMI and objective response rate, did not significantly differ between the two groups. The median total number of cycles of PEM therapy was significantly higher for the high-GNRI group (n [range]: 6 [2-20] vs. 3 [1-6]). The median CSS with second-line PEM therapy was 3.6 months (95% confidence interval [CI]: 2.5-6.1) and 11.8 months (95% CI: 6.2-NA) in the low-GNRI and the high-GNRI group (p < 0.01), respectively. Significant differences in CSS between the low- and high-CRP or -NRL groups were not found. Multivariate Cox proportional-hazards regression analysis revealed that a poor Eastern Cooperative Oncology Group performance status, visceral metastasis, and a low GNRI were significant prognostic factors for short CSS (95% CI: 1.62-6.10, HR: 3.14; 95% CI: 1.13-8.11, HR: 3.03; 95% CI: 1.32-8.02, HR: 3.25, respectively). Of the AEs, fatigue showed a significantly higher incidence in the low-GNRI group. CONCLUSIONS: For mUC patients receiving second-line PEM therapy, the GNRI is a useful predictive biomarker for survival outcome.

Prognostic significance of hyponatremia induced by systemic chemotherapy in a hospital-based propensity score-matched analysis.

BACKGROUND: During chemotherapy, hyponatremia is one of the most frequently encountered adverse effects. This study aimed to investigate the prognostic impact of hyponatremia induced by systemic chemotherapy (HIC) using a propensity matching method in cumulative pooled data. METHODS: Between January 2011 and July 2017, 2129 patients were administered systemic chemotherapy for malignancy in various organs at Nagoya City University Hospital. Patients were divided into two groups: a grade 0-1 group (control group) and a grade 3-4 group (severe group) according to the severity of HIC appearing within 30 days after starting treatment. Kaplan-Meier curves were used for survival and recurrence analyses using a propensity case-matched analysis. RESULT: The number of severe HIC patients was 93 (4.4%). In platinum-containing regimens, HIC appeared at higher frequencies. In the 21.2 months median follow-up period, the median OS (mOS) in the severe group was 49.1 months, which was significantly worse than the mOS in the control group; the OS in the control group did not reach the median. Univariate and multivariate analyses of associated factors in patients with grade 3-4 HIC revealed that renal dysfunction, cisplatin-containing regimen, and infusion of more than 5000 mL fluid was associated with HIC. CONCLUSION: This study suggests that severe HIC in the first treatment cycle affects survival time. Chemotherapy patients receiving extensive hydration should be required to undergo frequent monitoring of serum sodium levels, especially patients receiving platinum-containing regimens.

Antimicrobial susceptibility of pathogens in acute uncomplicated cystitis cases in the urology department of a community hospital in Japan: Comparison with treatment outcome and hospital-wide antibiogram.

We hypothesized that cases of uncomplicated cystitis treated in a Urology Department would display higher antimicrobial susceptibility than those reported by the hospital antibiogram. This would suggest narrow spectrum antibiotics could still be an effective treatment for uncomplicated cystitis despite this era of antimicrobial resistance. The objective of this study was thus to evaluate the rates of antimicrobial susceptibility of isolates cultured from uncomplicated cystitis cases that presented to the Urology Department of a community hospital in Japan. We evaluated the efficacy of cefaclor, a narrow spectrum antibiotic, for uncomplicated cystitis. We further compared the rates of antimicrobial susceptibility of isolates from uncomplicated cystitis cases to those reported in a hospital-wide antibiogram. A retrospective chart review was performed of patients diagnosed with uncomplicated cystitis in the Urology Department. The patients were mainly treated orally by cefaclor at 750 mg/day for seven days. Significantly greater susceptibilities to cefazolin (87.0% vs 65.7%), trimethoprim-sulfamethoxazole (89.4% vs 79.1%) and levofloxacin (84.6% vs 66.9%) were observed in a cystitis antibiogram for Escherichia coli compared with a hospital-wide antibiogram. The clinical efficacy of cefaclor for acute cystitis was also demonstrated. The greater susceptibility of Escherichia coli to antimicrobials observed in this study supports the hypothesis that antimicrobial susceptibility rates in uncomplicated cystitis cases that present to the Urology Department would be greater than those reported in the hospital antibiogram. Therefore, uncomplicated acute cystitis can be treated by narrow spectrum antibiotics such as cefaclor even in this ''antimicrobial resistance era''.