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This systematic review and meta-analysis aimed to assess and compare the perioperative and oncological outcomes of intracorporeal (ICUD) and extracorporeal (ECUD) urinary diversion following robot-assisted radical cystectomy (RARC). A systematic literature search of articles was performed in PubMed®, Web of Science®, and Scopus® databases according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. We included studies that compared patients who underwent RARC with ICUD to those with ECUD. Twelve studies including 3067 patients met the eligibility criteria. There were no significant differences between ICUD and ECUD in overall and major complications, regardless of the period (short-term [≤ 30 days] or mid-term [> 30 days]). Subgroup analyses demonstrated that ICUD performed by high-volume centers exhibited a significantly reduced risk of major complications (short-term: OR 0.57, 95% CI 0.37–0.86, p = 0.008, mid-term: OR 0.66, 95% CI 0.46–0.94, p = 0.02). Patients who underwent ICUD had lower estimated blood loss (MD -102.3 ml, 95% CI − 132.8 to − 71.8, p < 0.00001), less likely to receive blood transfusion rates (OR 0.36, 95% CI 0.20–0.62, p = 0.00003); and these findings were consistent in subgroup analyses by low-volume centers (MD-121.6 ml, 95% CI − 160.9 to − 82.3, p < 0.00001 and OR 0.36, 95% CI 0.20–0.62, p = 0.00003, respectively). ICUD had a higher lymph node yield (MD 3.68, 95% CI 0.80–6.56, p = 0.01). Patients receiving ICUD provided comparable complications, superior perioperative outcomes, and similar oncological outcomes compared with ECUD. Centralization of patients may contribute to a reduction of postoperative complications, while maintaining the advantages.

BackgroundThe aim of this study is to compare the perioperative outcomes and learning curves between intracorporeal and extracorporeal urinary diversion at our medium-sized institution.MethodsBetween January 2018 and September 2020, a single surgeon at our institution performed 46 consecutive robot-assisted radical cystectomies with ileal conduit. We compared the perioperative outcomes between patients who underwent intracorporeal versus extracorporeal urinary diversion. We also investigated learning curves for the first and last 10 patients in each group.ResultsThe extracorporeal group had shorter overall operative time (P = 0.003) and urinary diversion time (P < 0.0001) than the intracorporeal group. The intracorporeal group had shorter length of hospital stay (P = 0.02). There was no difference in complication and readmission rates. The extracorporeal group demonstrated no difference between the first and last 10 patients for overall operative time or time for cystectomy, lymph node dissection, or urinary diversion. However, the intracorporeal group had shorter urinary diversion time for the last 10 patients compared with the first 10 patients. The first 10 patients in the extracorporeal group had shorter overall operative time than the first 10 in the intracorporeal group, but there was no difference for the last 10 patients.ConclusionsIntracorporeal urinary diversion requires longer overall operative time than extracorporeal diversion for the first 10 patients, due to longer urinary diversion time. However, there is no difference in overall operative time for the last 10 patients. The benefit of intracorporeal over extracorporeal urinary diversion was not confirmed at our medium-sized institution.

BackgroundContrast-enhanced CT is necessary before donor nephrectomy and is usually combined with a Tc-99m-mercapto-acetyltriglycine (MAG3) scan to check split renal function (SRF). However, all transplant programs do not use MAG3 because of its high cost and exposure to radiation. We examined whether CT volumetry of the kidney can be a new tool for evaluating SRF.MethodsSixty-three patients underwent live donor nephrectomy. Patients without a 1.0 mm slice CT or follow-up for <12 months were excluded leaving 34 patients’ data being analyzed. SRF was measured by MAG3. Split renal volume (SRV) was calculated automatically using volume analyzer software. The correlation between SRF and SRV was examined. The association between the donor’s postoperative estimated glomerular filtration rate (eGFR) and predicted eGFR calculated by MAG3 or CT volumetry was analyzed at 1, 3, and 12 months post nephrectomy.ResultsStrong correlations were observed preoperatively in a Bland–Altman plot between SRF measured by MAG3 and either CT cortex or parenchymal volumetry. In addition, eGFR after donation correlated with SRF measured by MAG3 or CT volumetry. The correlation coefficients (R) for eGFR Mag3 split were 0.755, 0.615, and 0.763 at 1, 3 and 12 months, respectively. The corresponding R values for cortex volume split were 0.679, 0.638, and 0.747. Those for parenchymal volume split were 0.806, 0.592, and 0.764.ConclusionMeasuring kidney by CT volumetry is a cost-effective alternative to MAG3 for evaluating SRF and predicting postoperative donor renal function. Both cortex and parenchymal volumetry were similarly effective.

A novel cancer vaccine consisting of 20 mixed peptides (KRM-20) was designed to induce cytotoxic T lymphocytes (CTL) against twelve different tumor-associated antigens. The aim of this phase II trial was to examine whether KRM-20 in combination with docetaxel and dexamethasone enhances the antitumor effects in patients with castration-resistant prostate cancer (CRPC). In this double-blind, placebo-controlled, randomized phase II study, we enrolled chemotherapy-naïve patients with CRPC from ten medical centers in Japan. Eligible patients were randomly assigned 1:1 centrally to receive either KRM-20 combined with docetaxel and dexamethasone (n = 25) or placebo with docetaxel and dexamethasone (n = 26). The primary endpoint was the difference in prostate-specific antigen (PSA) decline between each treatment. The rates of > 50% PSA decline in the two arms were similar (56.5% versus 53.8%; P = 0.851). Human leukocyte antigen (HLA)-matched peptide-specific immunoglobulin G (P = 0.018) and CTL (P = 0.007) responses in the KRM-20 arm significantly increased after treatment. The addition of KRM-20 did not increase toxicity. There were no between-group differences in progression-free or overall survival (OS). The addition of KRM-20 was safe, and similar PSA decline and HLA-matched peptide-specific CTL and IgG responses increased in combination with docetaxel and dexamethasone in CRPC patients. Subgroup analysis suggested that this treatment is favorable for CRPC patients with ≥ 26% lymphocytes or PSA levels of < 11.2 ng/ml, but further clinical trials comparing OS are required.

PurposeWe assessed the prognostic value of systemic immune-inflammation index (SII) to refine risk stratification of the heterogeneous spectrum of patients with non-muscle-invasive bladder cancer (NMIBC)MethodsIn this multi-institutional cohort, preoperative blood-based SII was retrospectively assessed in 1117 patients with NMIBC who underwent transurethral resection of bladder (TURB) between 1996 and 2007. The optimal cut-off value of SII was determined as 580 using the best Youden index. Cox regression analyses were performed. The concordance index (C-index) and decision curve analysis (DCA) were used to assess the discrimination of the predictive models.ResultsOverall, 309 (28%) patients had high SII. On multivariable analyses, high SII was significantly associated with worse PFS (hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.23–2.77; P = 0.003) and CSS (HR 2.53; 95% CI 1.42–4.48; P = 0.001). Subgroup analyses, according to the European Association of Urology guidelines, demonstrated the main prognostic impact of high SII, with regards to PFS (HR 3.39; 95%CI 1.57–7.31; P = 0.002) and CSS (HR 4.93; 95% CI 1.70–14.3; P = 0.005), in patients with intermediate-risk group; addition of SII to the standard predictive model improved its discrimination ability both on C-index (6% and 12%, respectively) and DCA. In exploratory intergroup analyses of patients with intermediate-risk, the improved discrimination ability was retained the prediction of PFS and CSS.ConclusionPreoperative SII seems to identify NMIBC patients who have a worse disease and prognosis. Such easily available and cheap standard biomarkers may help refine the decision-making process regarding adjuvant treatment in patients with intermediate-risk NMIBC.

Programmed cell death protein 1 (PD-1) blockade is a promising therapeutic strategy against prostate cancer. Nitroxoline has been found to have effective anticancer properties in several cancer types. We investigated the efficacy of a combination therapy involving nitroxoline and PD-1 blockade in a prostate cancer mouse model. In our analysis we found that nitroxoline inhibited the viability and proliferation of the mouse prostate cancer cell line RM9-Luc-PSA. Additionally, nitroxoline downregulated the expressions of phospho-PI3 kinase, phospho-Akt (Thr308), phospho-Akt (Ser473), phospho-GSK-3β, Bcl-2, and Bcl-xL. Nitroxoline also downregulated programmed death-ligand 1 (PD-L1) expression levels in prostate cancer cell line and tumor tissue. In our murine prostate cancer orthotopic model, nitroxoline plus PD-1 blockade synergistically suppressed tumor growth when compared with nitroxoline or PD-1 blockade alone, leading to reductions in tumor weight, bioluminescence tumor signals, and serum prostate-specific antigen levels. Furthermore, fluorescence-activated cell sorting analysis showed that the combination strategy significantly enhanced antitumor immunity by increasing CD44 CD62L CD8 memory T cell numbers and reducing myeloid-derived suppressor cell numbers in peripheral blood. In conclusion, our findings suggest that nitroxoline plus PD-1 blockade may be a promising treatment strategy in patients with prostate cancer.

BackgroundExcessive visceral fat may decrease renal function because of metabolic derangements. The aim of this study was to evaluate the impact of abdominal fat distribution on renal function of recipients after kidney transplantation using the visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT) ratio.MethodsSeventy-nine patients underwent living kidney transplantation from 2009 to 2017. Patients without a correct measurement of VAT and SAT, follow-up of < 6 months, or with kidney transplant rejection or a virus infection were excluded. VAT and SAT were calculated automatically by 3-D volume analyzer software in recipients prior to living kidney transplantation. Our primary aim was to identify abdominal fat distribution measured by CT associated with renal dysfunction (estimate glomerular filtration rate; eGFR < 45) at 6 month post renal transplantation in recipient.ResultsFifty-eight living kidney recipients were included in this retrospective study: 30 for the high VAT/SAT ratio group; 28 for the VAT/SAT low group. Multiple logistic regression analysis showed the VAT/SAT ratio and pre-donor eGFR were associated with eGFR < 45 ml/min/1.73 m2. An increase in VAT/SAT ratio was associated independently with the incidence of decreased renal function.ConclusionThis finding indicates that adipose tissue distribution is an important predictor of the outcome of living kidney transplantation in recipients.

To determine the impact of sarcopenia on erectile functional outcomes after a nerve-sparing (NS) robot-assisted radical prostatectomy (RARP) using patient-reported validated questionnaires. In this retrospective study, RARP was performed on 841 patients at Okayama University Hospital, of which 132 underwent NS RARP. Erectile functional outcomes were assessed using the 5-item version of the International Index of Erectile Function (IIEF-5) and the Expanded Prostate Cancer Index Composite before and 1, 3, 6, and 12 months after surgery. Automated measurement of skeletal muscle at L3 was achieved using volume analyzer software and normalizing for height (cm²/m²) to calculate skeletal muscle index (SMI). Patients who had an IIEF-5≤4 comprised the group with erectile dysfunction (ED), and those with an IIEF-5≤5 made up the non-ED group. This study enrolled 95 patients of median age 65 years with a preoperative IIEF-5 of 16. There were no significant differences between patients with and without sarcopenia among those with preoperative IIEF-5. Postoperatively, in the ED group, SMI and preoperative IIEF-5 were significantly lower than in the non-ED group. Multiple linear regression analysis revealed that (1) both SMI and preoperative IIEF-5 were independent predictors of ED, and (2) sarcopenia and preoperative IIEF-5 were predictors of ED at 12 months after NS RARP. Patients with sarcopenia can have worse erectile functional outcomes after NS RARP. Sarcopenia and a lower preoperative IIEF-5 score may be predictive of postoperative ED.

This study aimed to compare the interobserver variabilities in magnetic resonance imaging (MRI)/computed tomography (CT) fusion image–based post-implant dosimetry of permanent prostate brachytherapy (PPB) between 1.5-T and 3.0-T MRI. The study included 60 patients. Of these patients, 30 underwent 1.5-T MRI and CT 30 days after seed implantation (1.5-T group), and 30 underwent 3.0-T MRI and CT 30 days after seed implantation (3.0-T group). All patients received PPB alone. Two radiation oncologists performed MRI/CT fusion image–based post-implant dosimetry, and the interobserver variabilities of dose–volume histogram (DVH) parameters [dose (Gy) received by 90% of the prostate volume (prostate D90)], percentage of the prostate volume receiving at least the full prescribed dose (prostate V100), percentage of the prostate volume receiving at least 150% of the prescribed dose (prostate V150), dose (Gy) received by 5% of the urethral volume (urethral D5) and the urethral volume receiving at least 150% of the prescribed dose (urethral V150)] were retrospectively estimated using the paired Student’s t test and Pearson’s correlation coefficient. The Pearson’s correlation coefficients of all DVH parameters were higher in the 3.0-T group than in the 1.5-T group (1.5-T vs 3.0-T: prostate D90, 0.65 vs 0.93; prostate V100, 0.62 vs 0.82; prostate V150, 0.97 vs 0.98; urethral D5, 0.92 vs 0.93; and urethral V150, 0.88 vs 0.93). In the paired Student’s t test, no significant differences were observed in any of the DVH parameters between the two radiation oncologists in the 3.0-T group (0.068 ≤ P ≤ 0.842); however, significant differences were observed in prostate D90 (P = 0.004), prostate V100 (P = 0.011) and prostate V150 (P = 0.002) between the oncologists in the 1.5-T group. The interobserver variability of DVH parameters in the MRI/CT fusion image–based post-implant dosimetry analysis of brachytherapy was lower with 3.0-T MRI than with 1.5-T MRI.

Prostate cancer is usually androgen‐dependent and responds well to androgen ablation therapy based on castration. However, at a certain stage some prostate cancers eventually acquire a castration‐resistant phenotype where they progress aggressively and show very poor response to any anticancer therapies. To characterize the molecular features of these clinical castration‐resistant prostate cancers, we previously analyzed gene expression profiles by genome‐wide cDNA microarrays combined with microdissection and found dozens of trans‐activated genes in clinical castration‐resistant prostate cancers. Among them, we report the identification of a new biomarker, stanniocalcin 2, as an overexpressed gene in castration‐resistant prostate cancer cells. Real‐time polymerase chain reaction and immunohistochemical analysis confirmed overexpression of stanniocalcin 2, a 302‐amino‐acid glycoprotein hormone, specifically in castration‐resistant prostate cancer cells and aggressive castration‐naïve prostate cancers with high Gleason scores (8–10). The gene was not expressed in normal prostate, nor in most indolent castration‐naïve prostate cancers. Knockdown of stanniocalcin 2 expression by short interfering RNA in a prostate cancer cell line resulted in drastic attenuation of prostate cancer cell growth. Concordantly, stanniocalcin 2 overexpression in a prostate cancer cell line promoted prostate cancer cell growth, indicating its oncogenic property. These findings suggest that stanniocalcin 2 could be involved in aggressive phenotyping of prostate cancers, including castration‐resistant prostate cancers, and that it should be a potential molecular target for development of new therapeutics and a diagnostic biomarker for aggressive prostate cancers. (Cancer Sci 2009; 100: 914–919)