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The Vesical Imaging Reporting and Data System (VI-RADS) was launched in 2018 to standardize reporting of magnetic resonance imaging for bladder cancer. This study aimed to prospectively validate VI-RADS using a next-generation magnetic resonance imaging scanner and to investigate the usefulness of denoising deep learning reconstruction.We prospectively enrolled 98 patients who underwent bladder multiparametric magnetic resonance imaging using a next-generation magnetic resonance imaging scanner before transurethral resection of bladder tumor. Tumors were categorized according to VI-RADS, and we ultimately analyzed 68 patients with pathologically confirmed urothelial bladder cancer. We used receiving operating characteristic curve analyses to assess the predictive accuracy of VI-RADS for muscle invasion. Sensitivity, specificity, positive/negative predictive value, accuracy and area under the curve were calculated for different VI-RADS score cutoffs.Muscle invasion was detected in the transurethral resection of bladder tumor specimens of 18 patients (26%). The optimal cutoff value of the VI-RADS score was determined as ≥4 based on the receiver operating curve analyses. The accuracy of diagnosing muscle invasion using a cutoff of VI-RADS ≥4 was 94% (AUC 0.92). Additionally, we assessed the utility of denoising deep learning reconstruction. Combination with denoising deep learning reconstruction significantly improved the AUC of category by T2-weighted imaging, and of the 4 patients who were misdiagnosed by the final VI-RADS score 3 were correctly diagnosed by T2-weighted imaging+denoising deep learning reconstruction.In this prospective validation study with a next-generation magnetic resonance imaging scanner, VI-RADS showed high predictive accuracy for muscle invasion in patients with bladder cancer before transurethral resection of bladder tumor. Combining T2-weighted imaging with denoising deep learning reconstruction might further improve the diagnostic accuracy of VI-RADS.

Since the Gleason score was developed in 1966 as a histological classification for prostate cancer, it has been widely used in clinical practice and has evolved over time. The concept of a "tertiary Gleason pattern" (also known as a minor Gleason pattern) was first proposed in 2000, and has been used in clinical practice since the 2005 International Society of Urological Pathology conference. The prognostic significance of a tertiary Gleason pattern has been widely validated in various settings of prostate cancer, whereas its definition has yet to be fully established. Currently, a provisional definition of tertiary Gleason pattern is "

For the past decade, sarcopenia has been actively investigated in various cancers, including urothelial carcinoma (UC). Although skeletal muscle index (SMI) is the main parameter used to evaluate sarcopenia in oncology, the optimal definition of SMI-based sarcopenia is not entirely standardized. We recently highlighted the potential limitations of current definitions of SMI-based sarcopenia in another journal. In this study, we reviewed studies that assessed sarcopenia in UC patients. We then performed a comparative validation of three major SMI-based definitions of sarcopenia, including Prado's, the international and Martin's definitions in metastatic UC patients. We believe that the standardization of the sarcopenia definition is an urgent issue in oncology, and this paper discusses a possible new direction to address this issue.

Although the treatment strategy for advanced urothelial carcinoma (aUC) has drastically changed since pembrolizumab was introduced in 2017, studies revealing current survival rates in aUC are lacking. This study aimed to assess (1) the improvement in survival among real-world patients with aUC after the introduction of pembrolizumab and (2) the direct survival-prolonging effect of pembrolizumab.This multicenter retrospective study included 531 patients with aUC undergoing salvage chemotherapy, including 200 patients treated in the pre-pembrolizumab era (2003-2011; earlier era) and 331 patients treated in a recent 5-year period (2016-2020; recent era). Using propensity score matching (PSM), cancer-specific survival (CSS) and overall survival (OS) were compared between the earlier and recent eras, in addition to between the recent era, both with and without pembrolizumab use, and the earlier era.After PSM, the recent era cohort had significantly longer CSS (21 months) and OS (19 months) than the earlier era cohort (CSS and OS: 12 months). In secondary analyses using PSM, patients treated with pembrolizumab had significantly longer CSS (25 months) and OS (24 months) than those in the earlier era cohort (CSS and OS: 11 months), whereas patients who did not receive pembrolizumab in the recent era had similar outcomes (CSS and OS: 14 months) as the earlier era cohort (CSS and OS: 12 months).Patients with aUC treated in the recent era exhibited significantly longer survival than those treated before the introduction of pembrolizumab. The improved survival was primarily attributable to the use of pembrolizumab.

We aimed to determine whether the presence of metabolic syndrome (MS) affects the efficacy of mirabegron in treatment-naïve women with overactive bladder (OAB).Women being treated with mirabegron 50 mg were allocated to MS and non-MS groups, and the efficacy of treatment of OAB was compared using the OAB symptom score (OABSS) and a 3-day voiding diary before and 12 weeks after starting treatment. The Wilcoxon signed-rank and Mann-Whitney U tests and multivariate logistic regression were used for statistical analyses, and a p-value0.05 was considered to represent statistical significance.Of the 197 patients who completed the trial, 43 (23.9%) had MS. After 12 weeks of mirabegron treatment, both the MS and non-MS groups showed significant improvements in OABSS score, the number of incontinence episodes/24 h, the number of micturition episodes/24 h, and the number of episodes of urgency/24 h. The factors associated with clinically important differences in OABSS were the presence of hyperglycemia (odds ratio 2.43, 95% confidence interval [CI] 1.05-5.60) and OABSS score at baseline (odds ratio 1.23, 95% CI 1.09-1.39).Mirabegron is effective in patients with and without MS, and comorbid hyperglycemia and severe OAB symptoms before treatment are predictors of the efficacy of mirabegron treatment.

Purpose Urinary incontinence (UI) is a common health-related problem in the female population and has a negative impact on many aspects of patients' quality of life including mental problems. This study evaluated the mental effects of mid-urethral sling (MUS) surgery in female patients with stress UI or stress UI-dominant mixed UI. Patients and Methods Women with stress UI or stress UI-dominant mixed UI who underwent MUS surgery and were enrolled in this study and followed up for 12 months. The International Consultation of Incontinence Questionnaire-Short Form (ICIQ-SF) and the Hospital Anxiety and Depression Scale (HADS) at baseline and 12 months after the MUS to evaluate the efficacy of the surgery. Results At baseline, proportions of the patients with anxiety (HADS-Anxiety score of ≥8) and depression (HADS-Depression score of ≥8) were 21.6% (22/102) and 24.5% (25/102), respectively. At 12 months postoperatively, the median ICIQ-SF score, HADS-Anxiety score, and HADS-Depression score were significantly improved compared with their baseline values (p

Background Although the albumin-to-globulin ratio (AGR) is a promising biomarker for various malignancies, few studies have investigated its prognostic significance for upper tract urothelial carcinoma (UTUC). Methods This retrospective study conformed to the REporting recommendations for tumour MARKer prognostic studies (REMARK) guideline. We reviewed 179 patients with UTUC who underwent radical nephroureterectomy at our institution between 2008 and 2018. Associations of preoperative clinicopathological factors, including the AGR, with cancer-specific survival (CSS) and overall survival (OS) were assessed. The Cox proportional hazards model was used for univariate and multivariable analyses. AGR was dichotomized as Results During a median follow-up of 34 months after surgery, 37 patients died from UTUC and 13 died of other causes. The preoperative AGR significantly correlated with pathological T stage, pathological N stage, and adjuvant chemotherapy. Multivariate analyses demonstrated that a decreased (P P Conclusions Preoperative AGR

Radical prostatectomy and external beam radiotherapy are recognized as comparable treatment options for localized prostate cancer. Previous studies of oncological outcomes of surgery versus radiotherapy have reported their comparability or possible superiority of surgery. However, the issue of which treatment is better remains controversial. Several factors make fair comparison of their outcomes difficult: different patient backgrounds caused by selection bias, different definitions of biochemical recurrence and different complication profiles between the treatment modalities. In 2016, the first large randomized controlled trial was published, which compared radical prostatectomy, external beam radiotherapy and active monitoring in localized prostate cancer. More recently, another study has reported comparative outcomes of robot-assisted radical prostatectomy and volumetric modulated arc therapy, as the leading surgery and radiotherapy techniques, respectively. Furthermore, there has been a trend toward combining external beam radiotherapy with brachytherapy boost, especially in patients with high-risk prostate cancer. This review summarizes the updated evidence on oncological outcomes of surgery versus external beam radiotherapy for localized prostate cancer.

Introduction In the Mayo Imaging Classification (MIC) for autosomal dominant polycystic kidney disease (ADPKD), the height-adjusted total kidney volume (HtTKV) growth rate is estimated for classification. Estimated HtTKV slope, termed as eHTKV-α, is calculated by the equation [HtTKV at age t] = K(1+α/100)(t-A), where K = 150 and A = 0 are used in MIC. If eHTKV-α is nearly stable during a standard-of-care period, the change in eHTKV-α from baseline can be used for estimation of the treatment effect on the HtTKV slope. Methods The constancy of eHTKV-α (A = 0 and K = 150) was evaluated using 453 placebo-assigned subjects in the Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 3:4 trial. A and K were sought out respectively by a converged pattern of regression lines of log10(HtTKV) plotted against age for subgroups divided according to MIC, and by change in eHTKV-α from baseline. A total of 239 standard-of-care patients from the Kyorin University Cohort (KUC) served as validation. Changes in eHTKV-α from baseline were evaluated in 809 tolvaptan-treated subjects in TEMPO 3:4. Results In placebo-assigned subjects, eHTKV-α (A = 0 and K = 150) changed significantly from baseline at the third year. As regression lines of placebo-assigned subgroups converged around age 0, A was set as 0, which was confirmed by KUC. K = 130 was selected because of minimal change in eHTKV-α from baseline. The KUC validated the constancy of eHTKV-α (A = 0 and K = 130) but not that of eHTKV-α (A=0 and K=150). In tolvaptan-treated subjects, eHTKV-α remained significantly lower than baseline for 3 years. Conclusions eHTKV-α (A = 0 and K = 130) was nearly stable from baseline through follow-up in standard-of-care adults. Treatment effects on the HtTKV slope can be estimated by changes in eHTKV-α from baseline.

Purpose: The aim of the present study was to evaluate the pathological and oncological outcomes of laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP) performed by one surgeon at a single center. Subjects: We evaluated 700 patients with localized prostate cancer (i.e., 250 received LRP and 450 received RARP) in the study. The clinicopathological outcomes, positive surgical margin (PSM) frequency, and biochemical recurrence (BCR)–free survival were compared between LRP and RARP. Results: At diagnosis, the median patient age and level of prostate-specific antigsen in the serum for LRP were 68 years and 8.1 ng/ml, respectively, while those for RARP were 66 years and 7.7 ng/ml, respectively. In the LRP group, the overall PSM rate was 31.2% (11.1% for pT2a, 19.0% for pT2b, 25.0% for pT2c, 60.0% for pT3a, 64.3% for pT3b, and 50% for pT4). In the RARP group, the overall PSM rate was 20.7% (4.8% for pT2a, 15.9% for pT2b, 12.9% for pT2c, 36.9% for pT3a, 46.2% for pT3b, and 100% for pT4). The PSM rate was significantly lower for RARP in men with pT2c, pT3a, or pT3b disease (p = 0.006, p = 0.009, and p = 0.027, respectively). Based on the multivariate analysis, RARP reduced the risk of BCR (hazard ratio = 0.8, p = 0.014). Conclusions: We compared the pathological findings and rates of BCR-free survival between patients who received LRP and those who received RARP at a single center. The rate of BCR-free survival was significantly higher in men classified as D'Amico high-risk patients who received RARP versus that reported in D'Amico high-risk patients who received LRP. Keywords: Laparoscopic radical prostatectomy, Oncological outcome, Robot-assisted radical prostatectomy

Background: Tolvaptan was approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD). However, the official indication of “rapidly progressive disease” is described differently in the clinical guidelines. We aim to define “rapidly progressive disease” by risk of ESRD, which is evaluated using estimated height-adjusted total kidney volume (HtTKV) growth rate. Methods: The risk of ESRD was retrospectively analyzed in 617 initially non-ESRD adults with ADPKD and observed with standard of care between 2007 and 2018. The estimated annual growth rate of the HtTKV, termed as eHTKV-α (%/year), is derived from the following equation: [HtTKV at age t] = K(1 + eHTKV-α/100)t, where K = 150 mL/m is used in Mayo Imaging Classification and K = 130 mL/m is proposed for individually stable eHTKV-α value from baseline. The accuracy of eHTKV-α to predict ESRD for censored ages was analyzed using time-dependent receiver-operating characteristic curves (ROC). The cutoff point of initially measured eHTKV-α to predict ESRD was assessed using Kaplan-Meier and Cox’s proportional hazards models. Performance characteristics of the cutoff point for censored ages were calculated using time-dependent ROC and validated by the bootstrap method. Results: The area under the time-dependent ROC of eHTKV-α to predict ESRD at age 65 was 0.89 ± 0.04 (K = 130). The mean renal survival was less than 70 years at eHTKV-α ≥4.0%/year (K = 130). Mean renal survival was approximately 12 years shorter, and hazard ratio of ESRD was more than 5-time higher at this cutoff point than at lower point. Time-dependent sensitivity for age 65 and cutoff point of 4.0%/year (K = 130) was 93.4 ± 0.3%. Between cutoff points ≥4.0%/year (K = 130) and ≥3.5%/year (K = 150), there was no significant difference in performance characteristics and accuracy to predict ESRD. Conclusion: eHTKV-α well predicts ESRD. Initially, measured eHTKV-α ≥4.0%/year (K = 130) defines high-risk ESRD. Without additional conditions, a single eHTKV-α cutoff point identifies subjects that are most likely to benefit from tolvaptan.

Transurethral resection of bladder tumor (TURBT) is the essential first step in the current algorithm for the management of bladder cancer (BC). However, despite its necessity and significance, TURBT has several limitations, including cost, hospitalization, anesthesia, potential complications such as bladder perforation, and delay to radical cystectomy. The Vesical Imaging Reporting and Data System (VI-RADS) was developed to standardize the reporting of multiparametric magnetic resonance imaging for BC, and its diagnostic accuracy to predict muscle invasion has been validated. Given the high sensitivity of VI-RADS ≥ 3 and high specificity of VI-RADS ≥ 4 as clinically relevant cutoff values, we herein propose a new VI-RADS-based algorithm for the management of BC. Using this algorithm, patients with VI-RADS ≤ 2 may not need to undergo sampling of the detrusor muscle nor second TURBT even if there is no muscle in the initial TURBT specimen, whereas patients with VI-RADS ≥ 4 may skip conventional TURBT aimed at pathologic confirmation of muscle invasion and immediately undergo radical cystectomy. Our newly proposed algorithm enables the avoidance of unnecessary deep resection or second TURBT as well as delay to radical cystectomy. The VI-RADS-based algorithm enables a paradigm shift from the current TURBT-dependent practice in the management of BC.

Background Adenosquamous carcinoma of the prostate (ASCP) is an extremely rare and aggressive prostate cancer variant, whose genomic characteristics have not been elucidated. Although liquid biopsy of circulating tumor cells (CTCs) is an emerging topic in oncology, no study has assessed CTCs in patients with ASCP. Case presentation. A 76-year-old man presented with discomfort in his urethra. His prostate-specific antigen (PSA) level was 13.37 ng/mL. A computed tomography (CT) scan indicated a prostate mass with multiple lymph node and lung metastases. The patient underwent transurethral resection of the prostate and prostatic needle biopsy; both specimens demonstrated Gleason grade group 5 acinar adenocarcinoma of the prostate. Bone scintigraphy indicated bone metastasis in the ischium. Combined androgen blockade was implemented, and his serum PSA level rapidly decreased to 0.01 ng/mL. However, a CT scan 6 months after the initial diagnosis revealed worsening of the disease. The patient therefore underwent repeated prostatic needle biopsy; its specimen demonstrated prostatic adenocarcinoma together with squamous carcinoma components. As immunohistochemical analyses showed the tumor cells to be negative for CD56, chromogranin A, synaptophysin, and PSA, the definitive diagnosis was ASCP. Although the patient underwent chemotherapy (docetaxel and cabazitaxel), he died of the disease 3 months after the diagnosis of ASCP, or 13 months after the initial diagnosis of prostatic adenocarcinoma. His PSA values remained ≤ 0.2 ng/mL. CTCs from the patient’s blood (collected before starting docetaxel) were analyzed and genomically assessed. It showed 5 cytokeratin (CK)+ CTCs, 14 CK− CTCs, and 8 CTC clusters, per 10 mL. Next-generation sequencing identified a total of 14 mutations in 8 oncogenes or tumor suppressor genes: PIK3CB, APC, CDKN2A, PTEN, BRCA2, RB1, TP53, and CDK12. Of 14 mutations, 9 (64%) were detected on CK− CTCs and 5 (36%) were detected on CK+ CTCs. Conclusions This is the first report of CTC analysis and genomic assessment in ASCP. Although the prognosis of ASCP is dismal due to lack of effective treatment, genomic analysis of CTCs might lead to effective treatment options and improved survival.

Background The ureterovesical junction is the boundary between the urinary bladder and upper urinary tract. Because treatment strategies for bladder cancer and upper tract urothelial carcinoma are entirely different, urothelial carcinoma involving the ureterovesical junction requires special attention. Nevertheless, studies focusing on the disease are lacking. Methods We reviewed consecutive patients with urothelial carcinoma treated via either transurethral resection of bladder tumor (n = 2791) or radical nephroureterectomy (n = 292) between 2000 and 2020 and identified those with bladder cancer involving the ureteral orifice (n = 64) and those with upper tract urothelial carcinoma involving the intramural ureter (≤2 cm) (n = 41). After excluding overlapping cases (n = 24), 80 patients with urothelial carcinoma involving the ureterovesical junction were analyzed. Results The initial symptoms or reasons for diagnosing urothelial carcinoma involving the ureterovesical junction were hematuria (n = 30), hydronephrosis (n = 21), follow-up examinations for prior urothelial carcinoma (n = 13), screening examinations (n = 7), frequent urination (n = 6) and unknown causes (n = 3). During a median follow-up period of 42 months, 18 patients died of urothelial carcinoma. The definitive surgical treatments for urothelial carcinoma involving the ureterovesical junction were transurethral resection of bladder tumor alone (n = 26), radical nephroureterectomy (n = 41) and radical cystectomy (n = 13), with different treatments having different cancer-specific survivals. Multivariate analyses identified T stage (≥T2) as an independent predictor of shorter cancer-specific survival. Conclusions Given the positional property of urothelial carcinoma involving the ureterovesical junction, the profiles of patients with the disease were highly heterogeneous. Further optimization of treatment strategies for urothelial carcinoma involving the ureterovesical junction is urgently warranted for better clinical outcomes.

Although radical prostatectomy and external beam radiotherapy are recognized as comparable treatment options for localized prostate cancer, robot-assisted radical prostatectomy (RARP) and volumetric modulated arc therapy (VMAT) as the leading respective techniques have yet to be compared.We retrospectively analyzed 860 patients with cT1-4N0M0 prostate cancer who underwent RARP (n = 500) or VMAT (n = 360) between 2011 and 2016. Biochemical recurrence-free survival (bRFS; two consecutive prostate-specific antigen measurements ≥0.2 ng/ml for RARP and Phoenix definition for VMAT) and radiological recurrence-free survival (rRFS; radiologically diagnosed distant metastasis or local recurrence) were compared between the two modalities. Cox proportional hazards model was used for multivariate analysis.The median follow-up durations were 30 and 47.5 months, and median ages were 67 and 71 years (both P 0.0001) in the RARP and VMAT groups, respectively. VMAT patients had significantly better bRFS than RARP patients, though their definitions of biochemical recurrence differed. If a unified definition of biochemical recurrence (two consecutive prostate-specific antigen measurements ≥0.2 ng/ml) was applied, RARP patients had significantly better bRFS than VMAT patients. Regarding rRFS, RARP patients had significantly better outcomes than VMAT patients, however, multivariate analysis together with D'Amico's risk classification, age-adjusted Charlson's comorbidity index, and concomitant androgen-deprivation therapy, demonstrated no significant difference between RARP and VMAT.The rRFS outcomes of RARP and VMAT after a medium-term follow-up period were similar, despite their different patient backgrounds. Further studies with a longer follow-up period are needed to compare these techniques in terms of cancer-specific and overall survivals.

The most impressive initiative for polar scientific research in India is conspicuously evident from the execution of meticulously designed polar research programmes embedded with diverse style of their research applicability, which was successfully implemented in order to usher a new era of polar research in India by late Dr. S. Z. Qasim, a pioneering doyen of the Indian polar programme. His tireless contributions to polar science programme opened up new avenues to make significant advances in geophysical and geological observational network of the polar regions (Arctic and Antarctic) that helped achieve scientific breakthrough involving global issues and their impacts to climate science. In order to commemorate his pertinent contributions in polar scientific research, we organize and publish this special issue of Polar Science on “Recent advances in climate science of polar region”.

Objectives the prevalence of intracranial aneurysms and arachnoid cysts is higher in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the general population. A genotype correlation was reported for intracranial aneurysms, but it is unclear for arachnoid cysts. Therefore, the genotype correlation with intracranial aneurysms and arachnoid cysts was investigated in ADPKD. Materials and Methods intracranial aneurysms and arachnoid cysts were screened by magnetic resonance imaging (MRI), and PKD genotypes were examined using next-generation sequencing for 169 patients with ADPKD. Results PKD1-, PKD2- and no-mutation were identified in 137, 24 and 8 patients, respectively. Intracranial aneurysms and arachnoid cysts were found in 34 and 25 patients, respectively, with no significant difference in frequency. Genotype, sex, estimated glomerular filtration rate and age at ADPKD diagnosis significantly affected the age at brain MRI. The proportional hazard risk analyzed using the age at brain MRI adjusted by these four variables was 5.0-times higher in the PKD1 group than in the PKD2 group for arachnoid cysts (P = 0.0357), but it was not different for intracranial aneurysms (P = 0.1605). Arachnoid cysts were diagnosed earlier in the PKD1 group than in the PKD2 group (54.8 vs 67.7 years, P = 0.0231), but no difference was found for intracranial aneurysms (P = 0.4738) by Kaplan-Meier analysis. Conclusions this study demonstrated the correlation between arachnoid cysts and PKD1 mutation. The reported association of arachnoid cysts with advanced renal disease may be due to the common correlation of these factors with PKD1 mutation.

The purpose of this study was to investigate the association between xanthine oxidoreductase (XOR) activity and a high risk of cardiovascular disease (CVD) in a general Japanese population. The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a general population-based cohort study in Iwate prefecture. The cardiovascular risk was calculated using the Framingham risk score (FRS). A total of 1605 of the 1631 participants (98.4%) had detectable XOR activity. Multiple regression analysis demonstrated that XOR activity was independently associated with body mass index (β = 0.26, p &lt, 0.001), diabetes (β = 0.09, p &lt, 0.001), dyslipidemia (β = 0.08, p = 0.001), and uric acid (β = 0.13, p &lt, 0.001). Multivariate analysis showed that the highest quartile of XOR activity was associated with a high risk for CVD (FRS ≥15) after adjustment for baseline characteristics (OR 2.93, 95%CI 1.16–7.40). The area under the receiver operating characteristic curves of the FRS with XOR activity was 0.81 (p = 0.008). XOR activity is associated with a high risk for CVD, suggesting that high XOR activity may indicate cardiovascular risk in a general Japanese population.

Introduction: Management of patients with atypical urinary cytology (class III) of the upper urinary tract is often complicated because some patients develop upper urinary tract urothelial carcinoma (UTUC). Here, we aimed to help define the optimal management of these patients. Methods: We investigated 31 patients who underwent retrograde ureteropyelography (RP) and were diagnosed with atypical findings of upper urinary tract cytology. Results: UTUC was revealed in 17 of 31 patients during the follow-up period of 1 year or longer. Tumor-like lesions and wall thickening in the upper urinary tract on initial computed tomography (CT) were significant predictors of UTUC (p = 0.0002 and p = 0.012, respectively). All 11 patients with tumor-like lesions and 3 of 8 patients with wall thickening on initial CT underwent nephroureterectomy, and UTUC was confirmed histologically. Moreover, 3 of 12 patients with hydronephrosis only or with normal findings later went on to develop UTUC. Repeated RP performed within 6 months from the initial RP was able to distinguish patients with UTUC from those without, even in individuals with normal CT findings. Discussion/Conclusion: Repeated RP based on initial CT findings is recommended in patients with atypical urinary cytology of the upper urinary tract. Nephroureterectomy without repeated RP may be warranted in patients with tumor-like lesions on initial CT findings.

Acute kidney injury (AKI) is a serious postoperative complication that occurs following laparoscopic surgery. However, its association with robot-assisted radical prostatectomy (RARP), the gold standard surgery for prostate cancer, is controversial. The current cohort included 257 patients with prostate cancer who underwent either RARP (n=187) or open radical prostatectomy (ORP; n=70). Patient serum creatinine concentration was measured at the following six time points: Prior to surgery, on postoperative day 0 (immediately after surgery), on postoperative day 1, 3 months after surgery, 1 year after surgery and 2 years after surgery. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A total of 25 RARP and 0 ORP patients met the KDIGO criteria on postoperative day 0. On postoperative day 1, 3 RARP and 2 ORP patients met the criteria, suggesting that AKI after RARP was a transient phenomenon. At 1 and 2 years after surgery, 5 of 257 patients exhibited a significant increase in serum creatinine concentrations from baseline results. Clinicians should be aware of transient AKI occurring after RARP, rather than ORP, to ensure better perioperative management in patients undergoing radical prostatectomy.

Background While the new Gleason grade grouping (GGG), which started in 2016, has been widely validated in prostate cancer, it does not incorporate the concept of tertiary Gleason pattern 5. Furthermore, no study has “quantified” the individual risk of each Gleason pattern, including tertiary Gleason pattern 5, after radical prostatectomy. Methods We reviewed 1022 men with adjuvant-treatment-naïve prostate cancer who underwent radical prostatectomy between 2005 and 2017. The primary endpoint was biochemical recurrence-free survival, defined as two consecutive prostate-specific antigen measurements ≥0.2 ng/ml after surgery. The individual quantitative risk score (IQRS) of each amount (primary/secondary/tertiary) of each Gleason pattern (3/4/5) was calculated using the Cox regression model. On the basis of the IQRS, the modified Gleason grade grouping (mGGG) model was developed. As a robustness analysis of the mGGG model, salvage treatment-free survival was also assessed. Results During a median follow-up of 45 months, 229 of 1022 (22.4%) patients developed biochemical recurrence. The IQRS of each Gleason pattern was as follows: primary 5, 1.81 points (hazard ratio [HR] 6.13); secondary 5, 1.37 points (HR 3.92); tertiary 5, 0.87 points (HR 2.39); primary 4, 1.07 points (HR 2.91); secondary 4, 0.79 points (HR 2.21); and any Gleason pattern 3, 0 points (HR 1). Based on the IQRS, the mGGG model was developed, which classified patients into the following five groups: I (3 + 3 or less); II (3 + 4); III (4 + 3); IV (3 + 4 + t5, 4 + 3 + t5, 3 + 5, 5 + 3, and 4 + 4); V (4 + 4 + t5, 4 + 5, 5 + 4, and 5 + 5). The c-index for biochemical recurrence-free survival was significantly improved from 0.655 of the original GGG model to 0.672 of the mGGG model (P P Conclusions The quantitative risk of tertiary (

Background Acute pyelonephritis (APN) with obstructive uropathy often causes sepsis. Recently, sepsis was redefined using the sequential organ failure assessment (SOFA) score, based on the new Sepsis-3 criteria. We investigated predictors for sepsis using this new definition in patients with obstructive APN associated with upper urinary tract calculi. Methods We retrospectively evaluated patients who were admitted to our hospital for treatment of obstructive APN associated with upper urinary tract calculi. Blood and urine samples were collected before treatment of obstructive APN. Treatment included adequate antimicrobial therapy and emergency drainage to decompress the renal collecting system. We diagnosed sepsis using the new Sepsis-3 definition. We assessed predictors for sepsis by multivariate logistic regression analysis. Results Sixty-one patients were included in this study. Overall, all patients underwent emergency drainage, and 11 (18.0%) patients showed sepsis. There were no significant differences in performance status or comorbidities between sepsis and non-sepsis groups. Platelet count and serum albumin level were significantly lower in the sepsis group than in the non-sepsis group (p = 0.001 and p = 0.016, respectively). Procalcitonin (PCT) and presepsin (PSEP) levels were significantly higher in the sepsis group than in the non-sepsis group (p p p = 0.024) and PSEP elevation (OR = 13.13, p = 0.044) were independent predictors for sepsis. Conclusions Elevation of PCT and PSEP levels before treatment might predict the development of sepsis in patients with obstructive APN.

ObjectivesAlthough lymphovascular space invasion is a prognostic factor for the recurrence of resectable endometrial cancer, the differential impacts of lymphatic vessel invasion (LVI) and blood vessel invasion (BVI) on the recurrence of endometrial cancer are poorly described. We investigated the prognostic significance of LVI and BVI on the recurrence of endometrial cancer and their association with patterns of recurrence.MethodsWe retrospectively reviewed 376 patients with stage I to III endometrial cancer who underwent surgery with curative intent at our institution between 2007 and 2015. The associations of the presence of lymphovascular space invasion or LVI and BVI with recurrence-free survival and patterns of recurrence were evaluated.ResultsLymphovascular space invasion positivity was an independent prognostic factor for recurrence-free survival (hazards ratio [HR], 3.070; 95% confidence interval [CI], 1.404–6.824; P = 0.0048). However, when categorized by LVI versus BVI, the latter was a strong independent prognostic factor (HR, 2.697; CI, 1.288–5.798; P = 0.0081), whereas the former was not (HR, 1.740; CI, 0.795–3.721; P = 0.1637). Hematogenous metastasis was the most prevalent form of recurrence in endometrial cancer (24 [50%] of all 48 recurrent cases). Notably, 17 (19.5%) of 87 patients with BVI developed hematogenous metastases, compared with 7 (2.4%) of 289 without BVI (χ2 test, P < 0.0001).ConclusionsBlood vessel invasion rather than LVI was a strong predictor of postoperative recurrence in stage I to III endometrial cancer, probably due to its predisposition to hematogenous metastases.

Introduction Since pheochromocytomas present with various complications due to catecholamine hypersecretion, their perioperative management needs special attention. Case presentation A 45-year-old man visited our hospital with a complaint of abdominal swelling. Radiological and endocrinological assessments determined the tumor as a giant (>20 cm) cystic pheochromocytoma. After administration of doxazosin, the patient underwent radical surgery. Since the tumor was extremely large and fixed to surrounding structures, we punctured it and aspirated cystic fluid to improve the tumor's mobility. However, during the aspiration, the patient developed acute hypotension, which could be reversed by suction withdrawal and vasopressor administration. A similar event occurred during a second aspiration. Eventually, the tumor was successfully excised with negative surgical margin. The cystic fluid proved to contain extremely high concentrations of catecholamines, which might result in the hypotension. Conclusion We report the first case who developed acute hypotension due to aspiration of cystic fluid from giant pheochromocytoma.

Background: While semiannual 60 mg denosumab is a common treatment for osteoporosis, the impact of monthly 120 mg denosumab, the common treatment protocol for bone metastases from solid tumors, on bone metabolism is unclear. Materials and Methods: We reviewed 15 patients with bone-metastatic prostate cancer who initiated monthly 120 mg denosumab in conjunction with androgen deprivation therapy between 2013 and 2014. Bone mineral density (BMD) was measured at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry (DXA), before treatment and annually thereafter. Bone metabolism markers, including urine N-terminal telopeptide (uNTx) and bone type alkaline phosphatase (BAP), were monitored monthly. Results: Twelve of 15 (80%) patients had evaluable DXA before treatment, and of them, eight underwent DXA after a year of initiation without discontinuation of denosumab. Percent changes in BMD from baseline were +6.2% at the lumbar spine and +7.6% at the femoral neck, both of which were significant ncreases (both P

The future shoaling of surface mixed layer depth due to global warming will expose natural assemblages of phytoplankton to increased mean light. Under these conditions, photoprotective acclimation against high light can determine ecological success. We investigated photoprotective responses to sunlight and recovery from photodamage of photosystem II (PSII) in natural assemblages north and south of the Polar Front (PF). The decrease in the maximum quantum yield (Fv/Fm) of PSII during direct sunlight exposure for 2 h was moderated progressively by the enhancement of diatoxanthin synthesis. When the light-exposed cells were incubated under three reduced light conditions, Fv/Fm recovered to more than the initial values north of the PF but did not reach initial values south of the PF. Temperatures higher in the north than the south of the PF could have induced the faster recovery from photodamage of PSII in assemblages north of the PF. These northern assemblages may be able to acclimate to fast-changing light conditions.

To evaluate the efficacy of adjuvant systemic chemotherapy for locally advanced (pT3-4pN0/xM0) upper tract urothelial carcinoma (UTUC). We retrospectively reviewed the medical records of 109 patients with pT3-4pN0/xM0 UTUC who had undergone radical nephroureterectomy between 1996 and 2013 at our four institutions. The patients were divided into two groups: those who received adjuvant chemotherapy (AC group) and those who did not (surgery-alone: SA group). All chemotherapy regimens were cisplatin-based. Cox proportional hazards regression models addressed the associations between clinicopathological factors and recurrence-free survival (RFS) and cancer-specific survival (CSS). Forty-three (39.5%) out of the 109 patients underwent one to four cycles of adjuvant chemotherapy after nephroureterectomy. Median follow-up was 46.5 months. There were no significant differences in the background characteristics of the two groups, except for age. Recurrence developed in 11 (25.6%) and 29 (43.9%) patients in the AC and SA groups, respectively. Ultimately, six (14.0%) and 18 (27.3%) patients in the AC and SA groups, respectively, died of disease progression. On univariate analysis, hydronephrosis, nuclear grade, lymphovascular invasion, and adjuvant chemotherapy were significantly associated with both RFS and CSS. Charlson comorbidity index was associated only with CSS. On multivariate analysis, adjuvant chemotherapy was the only independent factor associated with improved RFS (p = 0.0178, HR = 0.41). Moreover, adjuvant chemotherapy (p = 0.0375, HR = 0.33), lower nuclear grade (p = 0.0070), and the absence of hydronephrosis (p = 0.0493) were independently associated with better CSS. Locally advanced (pT3-4pN0/xM0) UTUC patients who underwent cisplatin-based adjuvant chemotherapy demonstrated better RFS and CSS than those without adjuvant chemotherapy.

Oncolytic virus therapy has recently been recognized as a promising new option for cancer treatment. Oncolytic viruses replicate selectively in cancer cells, thus killing them without harming normal cells. Notably, T-VEC (talimogene laherparepvec, formerly called OncoVEXGM-CSF), an oncolytic herpes simplex virus type 1, was approved by the US Food and Drug Administration for the treatment of inoperable melanoma in October 2015, and was subsequently approved in Europe and Australia in 2016. The efficacies of many types of oncolytic viruses against urological cancers have been investigated in preclinical studies during the past decade, and some have already been tested in clinical trials. For example, a phase I trial of the third-generation oncolytic Herpes simplex virus type 1, G47Δ, in patients with prostate cancer was completed in 2016. We summarize the current status of clinical trials of oncolytic virus therapy in patients with the three major urological cancers: prostate, bladder and renal cell cancers. In addition to Herpes simplex virus type 1, adenoviruses, reoviruses, vaccinia virus, Sendai virus and Newcastle disease virus have also been used as parental viruses in these trials. We believe that oncolytic virus therapy is likely to become an important and major treatment option for urological cancers in the near future.

The aim of the present study was to elucidate the details of bone metastasis (BM) and the resulting skeletal-related events (SREs), and survival and prognostic factors, in urothelial cancer (UC) patients with BM. A total of 48 UC patients with BM who were treated at our institution between 1994 and 2013 were enrolled. Details of BM and SREs were investigated. The Kaplan–Meier method was used to estimate survival duration. Relationships between several clinical features and survival were analyzed using the log-rank test and the Cox hazard model. Of the 48 patients, 39 (81.3%) were male, with a median age at diagnosis of BM of 68 years [interquartile range (IQR), 61–75 years]. Frequent metastatic sites included the pelvis (31 patients, 64.6%) and spine (28, 58.3%). SREs occurred in 31 patients (64.6%) at a median duration of 0.9 months (IQR, 0.3–5.4 months) after diagnosis of BM, including radiation therapy (n = 23; 74.2%), spinal cord compression (n = 4; 12.9%), pathological fracture (n = 3; 9.7%) and hypercalcemia (n = 1; 3.2%). Median overall survival periods after diagnosis of BM and SREs were 6.2 and 5.6 months, respectively. On multivariate analysis, factors significantly associated with survival after BM were performance status [hazard ratio (HR) for ≥2 vs. 0–1, 4.94; P = 0.0003], liver metastasis (HR, 4.08; P = 0.0018), chemotherapy after BM (HR, 0.31; P = 0.0018), and use of bone-modifying agents (HR, 0.36; P = 0.0147). We revealed clinicopathological factors that are predictive of prognosis of UC patients with BM. Although the prognosis is poor, chemotherapy and bone-modifying agents may confer survival benefits.

Objectives To investigate intraocular pressure and visual function in patients with ocular diseases undergoing robot-assisted laparoscopic prostatectomy. Methods We carried out a prospective clinical study of patients undergoing robot-assisted laparoscopic prostatectomy for localized prostate cancer at The University of Tokyo Hospital from December 2015 to March 2017. An ophthalmologist measured intraocular pressure, and carried out visual field testing at 0-2 months before and 7 days after robot-assisted laparoscopic prostatectomy. During the surgery, an anesthesiologist measured intraocular pressure at specified time points. Results A total of 110 patients were enrolled and 98 eligible patients were analyzed; 37 were diagnosed with ocular diseases before robotic-assisted laparoscopic prostatectomy (17 with glaucoma, 20 with other ocular diseases). Intraocular pressure significantly increased during robot-assisted laparoscopic prostatectomy. Transient postoperative visual field defect was detected in 24 eyes of 17 patients, including six patients with ocular diseases at 7 days after surgery. At 3 months after surgery, one of 34 glaucomatous eyes and one of 40 eyes with non-glaucomatous ocular diseases continued to show visual field defect, although visual field defect in the remaining patients recovered to preoperative conditions within 3 months. Conclusions Our findings suggest that robot-assisted laparoscopic prostatectomy can be safely carried out in patients with ocular diseases, even those with glaucoma, after precautionary consultation with an ophthalmologist.

The purpose of the present study was to validate the new GRade, Age, Nodes and Tumor (GRANT) score for renal cell carcinoma (RCC) prognostication within a large population of patients. Within the Surveillance, Epidemiology, and End Results database, we identified patients with either clear-cell or papillary RCC, who underwent nephrectomy between 2001 and 2015. Harrell’s C-Index, calibration plot and decision curve analysis were used to validate the GRANT model using a five-risk group stratification (0 vs. 1 vs. 2 vs. 3 vs. 4 risk factors). The primary endpoint was overall survival (OS) at 60 months. The analyses were repeated according to the histologic subgroup. The overall population included 73217 cases; 60900 with clear-cell RCC and 12317 with papillary histology, respectively. According to a five-risk group stratification, 23985 patients (32.8%) had no risk factor (0), 35019 (47.8%) had only one risk factor (1), 13275 (18.1%) had risk score 2, 854 (1.2%) had 3 risk factors and 84 (0.1%) of cases had a GRANT score of 4, respectively. At 60 months, OS rates as determined by the GRANT score were respectively 94% (score 0) vs. 86% (score 1) vs. 76% (score 2) vs. 46% (score 3) vs. 16% (score 4). In both histologic subtypes, the GRANT score yielded good calibration and high net benefit. OS C-Index values were 0.677 and 0.650 for clear-cell and papillary RCC at 60 months after surgery, respectively. In conclusion, the GRANT score was validated with a five-risk group stratification in a huge population from the SEER database, offering a further demonstration of its reliability for prognostication in RCC.

Small cell carcinoma of the urinary bladder (SCCB) is known for its aggressive clinical features and poor prognosis. No prognostic factor has been established so far. The aim of this study was to assess the significance of possible prognostic factors, including serum neuron-specific enolase (NSE), an established biomarker for small cell lung carcinoma. We retrospectively reviewed 31 patients with primary SCCB treated at our eight affiliate institutions between 2001 and 2014. The association of various clinicopathological factors at diagnosis, including the serum NSE value, with cancer-specific survival (CSS) was assessed. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. Nineteen (61.3 %) died of SCCB during the follow-up, with a median survival time of 12.7 months. Prognostic factors were analyzed for the 25 patients after excluding six with missing data. Univariate analysis demonstrated that stage (extensive disease) and serum NSE ≥25 ng/ml were significantly associated with worse CSS. Multivariate analysis identified increased serum NSE value as a sole independent predictor of CSS (hazard ratio 18.52, p = 0.0022). Serum NSE value at diagnosis was an independent prognostic factor for primary SCCB and may serve as a useful biomarker in the management of SCCB.

The original version of this Article contained a typographical error in the Abstract. “According to a five-risk group stratification, 23985 patients (32.8%) had no risk factor (0), 35019 (47.8%) had only one risk factor (1), 13275 (18.1%) had risk score 2854 (1.2%) had 3 risk factors and 84 (0.1%) of cases had a GRANT score of 4, respectively.” now reads: “According to a five-risk group stratification, 23985 patients (32.8%) had no risk factor (0), 35019 (47.8%) had only one risk factor (1), 13275 (18.1%) had risk score 2, 854 (1.2%) had 3 risk factors and 84 (0.1%) of cases had a GRANT score of 4, respectively.” This has now been corrected in the PDF and HTML versions of the Article.

BACKGROUND/AIM The aim of this study was to demonstrate the clinical significance of latent Gleason pattern (GP) 5 occasionally found in prostatectomy specimens. MATERIALS AND METHODS Patients (n=605) undergoing radical prostatectomy were classified into three groups according to the presence of GP5 in the biopsy or in the prostatectomy specimens: 'GP5 negative', absence of GP in both specimens 'latent GP5', absence of GP5 in the biopsy specimen, but presense of GP5 in the prostatectomy specimen, and 'GP5 positive', presense of GP in both specimens. The characteristics of these three groups were analyzed. RESULTS There were 381 men in the GP5-negative group, 155 in the latent GP5 group, and 69 in the GP5-positive group. Low- or intermediate-risk for prostate cancer, latent GP5 and surgical margin positivity were independent predictors of biochemical recurrence (Hazard ratio (HR): 3.1, 5.8, respectively, p=0.001, 0.0002, respectively). CONCLUSION Latent GP5 is an important prognostic factor that should be evaluated in patients with low- and intermediate-risk for prostate cancer before the initiation of treatment.

Oncolytic virus therapy is a promising new option for cancer. It utilizes genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming normal cells. T-VEC (talimogene laherparepvec), a second-generation oncolytic herpes simplex virus type 1, was approved by the US Food and Drug Administration for the treatment of inoperable melanoma in 2015 and subsequently approved in Europe in 2016. Other oncolytic viruses using different parental viruses have also been tested in Phase III clinical trials and are ready for drug approval: Pexa-Vec (pexastimogene devacirepvec), an oncolytic vaccinia virus, CG0070, an oncolytic adenovirus, and REOLYSIN (pelareorep), an oncolytic reovirus. In Japan, as of May 2018, several oncolytic viruses have been developed, and some have already proceeded to clinical trials. In this review, we summarize clinical trials assessing oncolytic virus therapy that were conducted or are currently ongoing in Japan, specifically, T-VEC, the abovementioned oncolytic herpes simplex virus type 1, G47Δ, a third-generation oncolytic herpes simplex virus type 1, HF10, a naturally attenuated oncolytic herpes simplex virus type 1, Telomelysin, an oncolytic adenovirus, Surv.m-CRA, another oncolytic adenovirus, and Sendai virus particle. In the near future, oncolytic virus therapy may become an important and major treatment option for cancer in Japan.

Collecting (Bellini) duct carcinoma of the kidney is a rare lethal tumor, and its prognostic factors remain unclear. The present study investigated the prognostic significance of neutrophil-to-lymphocyte ratio, which has recently been recognized as a readily available prognostic marker in various malignancies, in patients with collecting duct carcinoma. Of 11 patients who were pathologically diagnosed with collecting duct carcinoma at our institution, nine died of collecting duct carcinoma, one died of a postoperative complication, and one was alive, with a median follow-up period of 6 (range: 0-97) months. Both univariate and multivariate analyses associated neutrophil-to-lymphocyte ratio ≥4 (median) with worse cancer-specific survival. Notably, the sole surviving patient maintained a low neutrophil-to-lymphocyte ratio (

Soil aggregate (SA) can be formed and stabilized when soil organic matter (SOM) is decomposed in the soil. However, the relationships between the SA dynamics and SOM with different decomposition rates have not been clarified. Therefore, this study examined the effects of the addition of polysaccharides to soil on SA formation and stability. A Japanese tropical soil was incubated for 99 d at 30 °C in a dark environment following the addition of 0.5% (w/w) starch or cellulose. The decomposition rates of the amendments, and SA formation and stability were evaluated by measuring soil respiration rates, and distribution fractions of soil aggregate sizes and mean weight diameter (MWD) of SA, respectively. The cumulative soil respirations with all treatments rapidly increased until Day 12 of the incubation. The initial slope of the cumulative soil respiration in the soil with starch was significantly higher than that in the soil with cellulose. In either soil with starch or cellulose, the fractions of macro-aggregates (>1000 μm in diameter) significantly increased, respectively, compared with control soil. However, the fractions of meso-aggregates (250–1000 μm) and nano-aggregate (

Several prognostic models predicting survival of patients with metastatic urothelial carcinoma (UC) have been developed; however, of them, the first model by Bajorin in 1999 is still the most representative and widely used, and validations of newer models are lacking. This study aimed to validate three major prognostic models for metastatic UC constructed based on clinical trials.We reviewed 200 patients with metastatic UC who received first-line chemotherapy at our five affiliate institutions between 2003 and 2011. Using this multi-institutional cohort, we validated the following models: the "Bajorin model," a model consisting of visceral metastasis and performance status; the "Apolo model," a nomogram including visceral metastasis, performance status, albumin and hemoglobin; and the "Galsky model," a nomogram including leukocyte count, number of sites of visceral metastases, site of primary tumor, performance status and lymph node metastasis. Harrell's c-index was calculated for each model. Cox proportional hazards regression model was used for multivariate analysis.Among 200 patients, 171 (85.5%) died during the follow-up, with a median survival of 12.0 months. Multivariate analysis demonstrated ECOG performance status, visceral metastasis and leukocyte count to be independent predictors of overall survival. C-index results (95% confidence interval) were Bajorin: 0.86 (0.74-0.95); Apolo: 0.89 (0.78-0.98); and Galsky: 0.82 (0.69-0.93).All models were demonstrated to have high external validities in real-world patients, and of them, the "Apolo model" achieved the highest c-index in the present population. Further studies with larger populations are needed for establishment of the next standard model.