C-Reactive Protein Is a Potential Prognostic Marker in Patient with Advanced or Metastatic Urothelial Carcinoma Treated with Enfortumab Vedotin: A Multi-Center Retrospective Study.

BACKGROUND: In the EV-301 trial, enfortumab vedotin prolonged survival in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based therapy and programmed cell death 1/programmed death-ligand 1 inhibitor. However, real-world Asian data are limited, and potential prognostic markers are non-existent. We aimed to investigate potential prognostic markers for enfortumab vedotin therapy in Asian patients. METHODS: We retrospectively enrolled 61 Japanese patients treated with enfortumab vedotin therapy at our hospital and affiliated hospitals between January 2019 and September 2023. RESULTS: Enrolled patients (38 men, 23 women; median age 74 [IQR: 68-79] years) had bladder cancer (26 patients) or upper-tract urothelial carcinoma (35 patients). Fifty-four patients reported adverse events (grade >3 in 12). Skin disorders, pruritus, and neuropathy were common adverse effects. The median overall survival was 17.1 months (95% confidence interval: 10.0-not applicable). In multivariate analysis, the C-reactive protein level was an independent marker predicting favorable overall survival with enfortumab vedotin. Patient characteristics did not differ between C-reactive protein-high and -low groups. CONCLUSIONS: Our study provides real-world data showing that enfortumab vedotin prolonged survival in Asian patients similar to the EV-301 trial. Additionally, the C-reactive protein level might be considered a prognostic marker of enfortumab vedotin therapy in such patients.

Proton pump inhibitors and potassium competitive acid blockers decrease pembrolizumab efficacy in patients with metastatic urothelial carcinoma.

We elucidated the efficacy of gut microbiome-altering drugs on pembrolizumab efficacy in patients with metastatic urothelial carcinoma (mUC). Clinical data were analyzed retrospectively from 133 patients with mUC who received second-line pembrolizumab therapy between January 2018 and January 2021, following failed platinum-based chemotherapy. We evaluated the effects of gut microbiome-altering drugs (proton pump inhibitors [PPI]/potassium-competitive acid blockers [P-CAB], H2 blockers, antibiotics, non-steroidal anti-inflammatory drugs [NSAIDs], metformin, antipsychotics, steroids, and opioids), taken by patients within 30 days before/after pembrolizumab treatment, on progression-free survival (PFS) and overall survival (OS). Fifty-one patients received PPI/P-CAB (37/14, respectively); H2 blockers, 7; antibiotics, 35; NSAIDs, 22; antipsychotics, 8; metformin, 3; steroids, 11; and opioids, 29. Kaplan-Meier curves revealed PPI or P-CAB users showed shorter PFS than non-PPI-P-CAB users (p = 0.001, p = 0.005, respectively). Multivariate analysis highlighted PPI/P-CAB use as the only independent prognostic factor for disease progression (hazards ratio: 1.71, 95% confidence interval: 1.14-2.07, p = 0.010) but not death (p = 0.177). Proton pump inhibitors/potassium-competitive acid blockers may decrease the efficacy of pembrolizumab therapy for mUC, possibly via gut microbiome modulation.

Heterozygous c.175C>T variant in PURA gene causes severe developmental delay.

Key Clinical Message: This case report presents a child with PURA-related neurodevelopmental disorder, caused by the heterozygous pathogenic variant c.175C>T (p.Gln59*). The clinical symptoms included microcephaly, brachygnathia, central and peripheral hypotonia, and developmental delay (non-verbal), among others. On comparison with published literature, even patients with the same mutation present different clinical symptoms. Abstract: This case report presents a child with PURA-related neurodevelopmental disorder, caused by the heterozygous pathogenic variant c.175C>T (p.Gln59*), whose symptoms included microcephaly, brachygnathia, the development of a high anterior hairline, hip dysplasia, strabismus, severe hypotonia, developmental delay (non-meaningful verbal), feeding difficulties, and respiratory difficulties. His development ceased with age, such that his development at 10 years corresponded to an infant of 6 months. Moreover, even patients with the same variant can have different clinical symptoms, such as the presence or absence of epilepsy or congenital malformations. Therefore, we should follow his long-term clinical course and provide medical support as necessary.

Dynamic cord compression induced by proximal junctional failure and loose pedicle screws after thoracolumbar fusion surgery: a case report.

BACKGROUND: One of the common mechanical complications following spinal fusion surgery is proximal junctional failure (PJF). The incidence of neurological deficit associated with PJF has been poorly described in the literature. Here, we report a case in which numbness in the lower extremities was recognized as the first symptom, but the discrepancy in the imaging findings made PJF difficult to diagnose. METHODS: A 71-year-old female underwent corrective fusion surgery. Three weeks later, she complained of persistent right leg numbness. Standing X-ray showed the back-out of the pedicle screws (PSs) in the upper instrumented vertebra (UIV), but there was no obvious evidence of cord compression on computed tomography (CT), which caused the delay of diagnosis. Five weeks later, magnetic resonance image (MRI) did not show cord compression on an axial view, but there were signal changes in the spinal cord. RESULTS: The first reason for the delayed diagnosis was the lack of awareness that leg numbness could occur as the first symptom of PJF. The second problem was the lack of evidence for spinal cord compression in various imaging tests. Loosened PSs were dislocated on standing, but were back to their original position on supine position. In our case, these contradictory images led to a delay in diagnosis. CONCLUSION: Loosened PSs caused dynamic cord compression due to repeated deviation and reduction. Supine and standing radiographs may be an important tool in the diagnosis of PJF induced by dynamic cord compression.

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.

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.

Spinopelvic fusion surgery from lower thoracic spine to pelvis increased hip joint moment-motion analysis.

PURPOSE: Spinal fusion surgery is often performed with pelvic fixation to prevent distal junctional kyphosis. The inclusion of spinopelvic fixation has been reported to induce progression of hip joint arthropathy in a radiographic follow-up study. However, its biomechanical mechanism has not yet been elucidated. This study aimed to compare the changes in hip joint moment before and after spinal fusion surgery. METHODS: This study was an observational study and included nine patients (eight women and one man) who were scheduled to undergo spinopelvic fusion surgery. We calculated the three-dimensional external joint moments of the hip during gait, standing, and climbing stairs before and 1 year after surgery. RESULTS: During gait, the maximum extension moment was 0.51 ± 0.29 and 0.63 ± 0.40 before and after spinopelvic fusion surgery (p = 0.011), and maximum abduction moment was 0.60 ± 0.33 and 0.83 ± 0.34 before and after surgery (p = 0.004), respectively. During standing, maximum extension moment was 0.76 ± 0.32 and 1.04 ± 0.21 before and after spinopelvic fusion surgery (p = 0.0026), and maximum abduction moment was 0.12 ± 0.20 and 0.36 ± 0.22 before and after surgery (p = 0.0005), respectively. During climbing stairs, maximum extension moment was - 0.31 ± 0.30 and - 0.48 ± 0.15 before and after spinopelvic fusion surgery (p = 0.040), and maximum abduction moment was 0.023 ± 0.18 and - 0.02 ± 0.13 before and after surgery (p = 0.038), respectively. CONCLUSION: This study revealed that hip joint flexion-extension and abduction-adduction moments increased after spinopelvic fixation surgery in the postures of standing, walking, and climbing stairs. The mechanism was considered to be adjacent joint disease after spinopelvic fusion surgery including sacroiliac joint fixation.

Salvage Surgery for Symptomatic Recurrence of Retro-Odontoid Pseudotumor after a C1 Laminectomy.

We provide the first report of successful salvage surgery for a post-C1 laminectomy symptomatic recurrence of a retro-odontoid pseudotumor (ROP) that caused myelopathy. The 72-year-old Japanese woman presented with an ROP causing symptomatic cervical myelopathy. With ultrasonography support, we performed the enucleation of the ROP via a transdural approach and fusion surgery for the recurrence of the mass. At the final observation 2-year post-surgery, MRI demonstrated the mass's regression and spinal cord decompression, and the patient's symptoms had improved. Our strategy is an effective option for a symptomatic recurrence of ROP.

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.

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.

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.

Modified Glasgow Prognostic Score 2 as a Prognostic Marker in Patients With Metastatic Urothelial Carcinoma.

BACKGROUND/AIM: Predicting the prognosis of metastatic urothelial carcinoma (mUC) patients is needed for clinical decisions. We examined the value of a modified Glasgow prognostic score (mGPS) as a predictive marker for mUC patients. PATIENTS AND METHODS: In a multicenter study, 68 mUC patients received short hydration gemcitabine/cisplatin (shGC) and 74 received pembrolizumab (PEM). Patients were allocated according to mGPS. Progression-free (PFS) and cancer-specific (CSS) survival were examined. RESULTS: Higher mGPS reflected poorer PFS and CSS in shGC (p=0.03, p<0.0001, respectively) and PEM (p=0.02, p<0.001, respectively) patients. PFS for the high mGPS group was longer than that of the low mGPS group in the two cohorts (p <0.0001 for both), with similar CSS results (p<0.0001 and p<0.001, respectively). Multivariate analyses revealed high mGPS was a risk factor for poor CSS in both cohorts (HR=3.55, p<0.001, and HR=2.21, p<0.01, respectively). CONCLUSION: In the mUC patients receiving shGC or PEM, mGPS was a predictive prognostic marker.

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.

UroVysion fluorescence in situ hybridization in urothelial carcinoma: a narrative review and future perspectives.

The number of patients with urothelial carcinoma (UC) is high, with a corresponding demand for detecting UC easily and non-invasively. Cystoscopy and urine cytology, with widely known diagnostic accuracies, are the gold standards for identifying UC originating from the bladder. However, cystoscopy or other tests, such as ureteroscopy or retrograde pyelography, are uncomfortable for patients. Tests for urinary biomarkers are expected to satisfy the demand for less invasive tests that will benefit patients with anxiety for invasive tests such as cystoscopy or ureteroscopy. Although several urinary biomarkers have been reported to support the diagnosis or follow-up of UC, their use in the clinic is uncommon. The UroVysion test examines urinary biomarkers using a multitarget, multicolor fluorescence in situ hybridization (FISH) assay. The test uses exfoliated cells found in urine and is a mixture of centromeric fluorescent denatured chromosome enumeration probes for chromosomes 3, 7, and 17 (labelled stratum red, spectrum green and spectrum aqua, respectively), and a locus-specific identifier probe for 9p21 (spectrum gold). It is used for the initial diagnosis of patients with hematuria or the monitoring of patients previously diagnosed with bladder cancer. Almost 20 years have passed since UroVysion was approved by the U.S. Food and Drug Administration, and so this is a well-established test. However, room exists for further research, with numerous reports on this test having been recently published. In order to update our knowledge, we herein present a brief overview of UroVysion and its features that follows the latest findings as they relate to UC.

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.

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.

Rare case of carcinoma in situ originated in right retrocaval ureter successfully managed with laparoscopic procedure.

INTRODUCTION: A retrocaval ureter is a rare congenital abnormality characterized by the persistence of the posterior subcardinal vein on the right, which causes the proximal ureter to deviate medially behind the inferior vena cava. The presence of retrocaval ureter is usually found because of the development of progressive hydronephrosis, but many cases are clinically silent. In addition, an urothelial malignancy associated with retrocaval ureter is very rare. CASE PRESENTATION: Herein we report a very rare case of a 57-year-old male with retrocaval ureter and carcinoma in situ diagnosed by ureteroscopy. In spite of strong adhesion in the area of the ureter behind the inferior vena cava, dissection was successfully managed by a laparoscopic procedure after cutting the ureter and separating it into two segments. CONCLUSION: Early histopathological diagnosis and radical laparoscopic surgery based on the results of ureteroscopy may lead to a good outcome, even in retrocaval ureter cases with a carcinoma in situ.

Improvement in early urinary continence recovery after robotic-assisted radical prostatectomy based on postoperative pelvic anatomic features: a retrospective review.

BACKGROUND: We investigated the impact of postoperative membranous urethral length and other anatomic characteristics of the pelvic floor shape as measured by magnetic resonance imaging on the improvement in continence following robotic-assisted radical prostatectomy. METHODS: We retrospectively reviewed data from 73 patients who underwent postoperative prostate magnetic resonance imaging following robotic-assisted radical prostatectomy between 2013 and 2018. Patient demographics; pre-, peri-, and post-operative parameters; and pelvic anatomic features on magnetic resonance imaging were reviewed. Patients who used no urinary incontinence pads or pads for protection were considered to have achieved complete continence. RESULTS: Urinary continence was restored in 27.4, 53.4, 68.5, and 84.9% of patients at 1, 3, 6, and 12 months after robotic-assisted radical prostatectomy, respectively. When patients were divided into early and late continence groups based on urinary continence at 3 months after robotic-assisted radical prostatectomy, no significantly different clinical characteristics or surgical outcomes were found. However, the mean membranous urethral length (18.5 mm for the early continence group vs. 16.9 mm for the late continence group), levator muscle width (7.1 vs. 6.5 mm, respectively), and bladder neck width on the trigone side (7.2 mm vs. 5.4 mm, respectively) were significantly different between groups (all p < 0.05). Multivariate logistic regression analysis showed that membranous urethral length (odds ratio, 1.227; 95% confidence interval, 1.011-1.489; p = 0.038) and bladder neck width (odds ratio, 1.585; 95% confidence interval, 1.050-2.393; p = 0.028) were associated with the period of early urinary continence. CONCLUSIONS: Postoperative membranous urethral length and bladder neck width were significantly associated with early urinary continence recovery after robotic-assisted radical prostatectomy. It is highly recommended that surgeons focus on preserving the membranous urethral length and increasing the bladder neck width on the trigone side during surgery to achieve optimal continence outcomes after robotic-assisted radical prostatectomy.

Cationic peptides from enzymatic hydrolysates of soybean proteins exhibit LPS-neutralizing and angiogenic activities.

In this study, we prepared fractions containing multifunctional cationic peptides by separating the commercial soybean protein hydrolysate Hinute-AM into 20 fractions. These fractions contained peptides with various isoelectric points (pI), as indicated by ampholyte-free isoelectric focusing (autofocusing). Thus, we purified and identified the cationic peptides from fractions 19 and 20, which had pH values greater than 10, using reversed-phase high-performance liquid chromatography and matrix-assisted laser/desorption ionization-time-of-flight mass spectroscopy. Among 19 identified cationic peptides, NKNAKPPSPR, PGKKNAIV, KSGPGMSPR, NVSKPPRVV, RKVGAGGRKPLG, and LPCVIGGVPKRV had high pI values and were included as chemically synthesized peptides in assays of various functions, including lipopolysaccharide (LPS)-neutralizing and angiogenic activities. Chromogenic LPS-neutralizing assays using Limulus amebocyte lysates showed that 50% effective concentrations of these six peptides were between 1.63 and 2.65 µM, and were higher than that (0.12 µM) of polymyxin B. Moreover, in tube-formation assays in human umbilical vein endothelial cells, all of the six cationic peptides except LPCVIGGVPKRV exhibited angiogenic activities similar to those of the positive control LL-37. In addition, the six identified cationic peptides had no hemolytic activity at concentrations up to 500 µM in mammalian red blood cells. Our results demonstrate that five of the identified cationic peptides, excluding LPCVIGGVPKRV, have multiple functions and little or no hemolytic activity. These data indicate that fractions containing cationic peptides from Hinute-AM have the potential to be used as dietary supplements and functional ingredients in food products.