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There are questions regarding whether grade group (GG) 4 prostate cancer (PC) is heterogeneous in terms of prognosis. We assessed prognostic differences in PC patients within GG 4 treated with radical prostatectomy (RP). Biochemical recurrence (BCR)-free, cancer-specific, and overall survival were analyzed in 787 PC patients with GG 4 based on RP pathology (Gleason score (GS) 3 + 5: 189, GS 4 + 4: 500, and GS 5 + 3: 98). Logistic regression analysis was performed to assess factors predictive of high-risk surgical pathological features. Cox regression models were used to evaluate potential prognostic factors of survival. Within a median follow-up of 86 months, 378 patients (48.0%) experienced BCR and 96 patients (12.2%) died, 42 of whom (5.3%) died of PC. GS 5 + 3 was significantly associated with worse BCR-free and cancer-specific survival, as well as higher positive surgical margin, lymph node metastasis, extraprostatic extension, and non-organ-confined disease rates, than GS 3 + 5 and higher positive surgical margin, lymph node metastasis, extraprostatic extension, and non-organ-confined disease rates than GS 4 + 4 (P < 0.05). GS 4 + 4 was significantly associated with worse BCR-free survival and higher extraprostatic extension, and non-organ-confined disease rates than GS 3 + 5 (P < 0.05). Inclusion of the different Gleason patterns improved the discrimination of a model for prediction of all survival outcomes compared to standard prognosticators. There is considerable heterogeneity within GG 4 in terms of oncological and surgical pathological outcomes. Primary and secondary Gleason patterns should be considered to stratify high-risk PC patients after RP. [ABSTRACT FROM AUTHOR]

Introduction Heparin-induced thrombocytopenia (HIT) is a rare but serious condition due to heparin use for treating thromboprophylaxis, regardless of the dosage. Here, we present a case of non-immune thrombocytopenia caused by thromboprophylaxis for urological surgery, which is sometimes difficult to discriminate from immune-mediated thrombocytopenia. Presentation of case A 55-year-old man with renal cancer underwent portless endoscopic radical nephrectomy through a single small incision and was subsequently administered unfractionated heparin as well as mechanical devices to prevent venous thromboembolism. On postoperative day 2, a subcutaneous hemorrhage developed around the surgical site and the lower abdomen, and the platelet count simultaneously decreased to 50% of the baseline value. We suspected HIT and immediately conducted the 4Ts score examination. The 4Ts score was 3 points (low probability), and the result of the platelet factor 4-heparin complex antibody assay was negative. The patient was diagnosed with non-immune mediated thrombocytopenia. We took precaution by discontinuing heparin, which fortunately did not result in any adverse effects, and this led to platelet count normalization. Discussion Due to the rarity of HIT, it is difficult to distinguish HIT from non-immune mediated thrombocytopenia. Conclusion This article emphasizes that early and accurate diagnosis of postoperative thrombocytopenia is important for accurate therapy. Hence, all surgeons should know that the HIT diagnosis is based on clinical and serologic findings. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To investigate the health-related quality of life of patients who underwent radical prostatectomy performed using retropubic, laparoscopic, and perineal approaches. Methods: A total of 218 men who underwent retropubic prostatectomy, 65 who underwent laparoscopic prostatectomy, and 66 who underwent perineal prostatectomy were enrolled in our survey. A baseline interview was conducted before treatment. Follow-up interviews were conducted in person at scheduled study visits 1, 3, 6, and 12 months after surgery. We measured two validated questionnaires that assessed the general and disease-specific health-related quality of life. Results: The retropubic group reported substantial deterioration in physical limitations, emotional limitations, social function, and bodily pain at 1 month. The perineal group reported less bodily pain just after surgery than the retropubic and laparoscopic groups. After 6 months, however, no significant differences were found among the three groups. Postoperative urinary function remained substantially lower than the baseline level in every treatment group. Each approach with a nerve-sparing procedure showed a similar recovery profile of urinary function postoperatively. The perineal group reported no significant difference in bowel function compared with the other two groups. All of the groups continued to have decrements in sexual function. Conclusions: The results of this study have demonstrated that retropubic, laparoscopic, and perineal prostatectomy have differences in the recovery of general and disease-specific quality of life in the early postoperative period. When performed by an experienced surgeon, the retropubic, laparoscopic, and perineal approaches appear to be equivalent in terms of health-related quality of life. [Copyright &y& Elsevier]

Abstract: Objectives: To compare the general and disease-specific health-related quality of life (HRQOL) after laparoscopic radical prostatectomy (LRP) with that after retropubic radical prostatectomy (RRP). Methods: A total of 45 patients who underwent LRP alone and 121 who underwent RRP alone were prospectively enrolled in an HRQOL survey. We measured the general and disease-specific HRQOL with the Medical Outcomes Study 36-Item Short Form and University of California, Los Angeles, Prostate Cancer Index, respectively. The participants were asked to complete the questionnaires before and 1, 3, 6, and 12 months after surgery. Results: No significant differences were found in the preoperative characteristics of the two groups. Repeated measures of analyses of variance revealed significantly different patterns of alteration in the several general HRQOL domains between the RRP and LRP groups. The LRP group tended to have a more delayed recovery than the RRP group in the domain of urinary function and bother. The sexual function and bother of both groups showed a substantially lower score throughout the postoperative period. When the LRP group was divided into two groups according to the surgical period, an apparent improvement in HRQOL was observed in the most recent LRP series. Conclusions: The two approaches showed different patterns of alteration regarding general HRQOL for 1 year after surgery. The LRP group reported delayed recovery of urinary and sexual function, which seemed to affect their general HRQOL. LRP appears to be still an evolving procedure. [Copyright &y& Elsevier]

We analyzed all 21 exons of the RET proto-oncogene of paired genomic DNA from tumors and normal tissues in 12 small cell lung cancer (SCLC) patients for the presence of genetic alteration. Polymerase chain reaction single-strand conformation polymorphism analysis and direct sequencing revealed that heterozygosity of the RET proto-oncogene was lost in the tumor tissues of six patients out of eight informative SCLC patients, although point mutation was not evident in any tumors. These results suggest that a deletion of the chromosomal region including the RET proto-oncogene is involved in the pathogenesis of SCLC. [Copyright &y& Elsevier]

Objectives. To determine the anatomic patterns of tumor distribution in radical prostatectomy specimens from nonpalpable prostate cancer.Methods. Tumor maps directly traced from histologic slides of 62 radical prostatectomy specimens were superimposed by a computer-assisted imaging technique to create an idealized prostate gland at three levels: apex, mid-prostate, and base. To investigate specific patterns of tumor distribution, the sites of tumor in each quadrant were compared according to risk group stratification. The tumor extent was compared with the patterns of positivity in routine sextant biopsies.Results. Among all patients, the tumor frequency was 85.5% in the mid-gland, 82.3% in the apex, and 48.4% in the base. Analysis by quadrant showed that tumors were significantly denser in the apex to mid-prostate. The primary extent of these tumors appeared to lie predominantly in the anterior half of the gland. Biopsy yields at the apex and mid-prostate appeared low compared with the frequency of cancers at these levels. No patterns specific to the different risk groups were found, but no tumors within the anterior base were found in the low-risk group.Conclusions. The primary extent of nonpalpable tumors appeared to lie predominantly in the anterior half of the gland at the apex to mid-prostate levels. Additional biopsy cores taken from more anterior regions of the gland may enhance the detection of nonpalpable cancers further. [Copyright &y& Elsevier]

We established a novel culture method for generating dendritic cells (DC) from mouse bone marrow (BM) cells. Unfractionated bulk BM cells were cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 5–7 days and a DC population was isolated by gradient centrifugation with 14.5% (w/v) metrizamide. Through this method, 30–40×106/mouse DC with 85–95% purity was obtained on day 7; this yield was higher than those of conventional DC generated by Inaba''s method either with GM-CSF alone (conventional-GM DC) or GM-CSF and IL-4 (conventional-GM/4 DC). Bulk-cultured DC have a more matured phenotype than both conventional-GM and -GM/4 DC as shown by higher expression of CD86, MHC class II and CD40. Functional analyses reveal that (1) bulk-DC show less ability in endocytosis than conventional-GM DC and are comparable in IL-12 p70 production with conventional-GM and -GM/4 DC. (2) Bulk-DC exhibit stronger stimulatory capacity in allogeneic T-cell proliferation than conventional DC. (3) By using ovalbumin (OVA) and OVA-specific T-cell receptor (TCR) transgenic mice (DO11.10) system, OVA protein-loaded bulk-DC stimulated CD4 T cells of DO11.10 mice more than conventional-GM DC and comparable with conventional-GM/4 DC. (4) Furthermore, OVA peptide-pulsed bulk-DC stimulated CD4 T cells more than conventional-GM and -GM/4 DC. These data indicate that bulk-DC are functionally more mature than conventional DC. Taken together, bulk-culture method is a simple technique for generating functionally mature BM–DC in large quantities and high purity. [Copyright &y& Elsevier]

Background: The programmed cell death ligand-1 (PD-L1)/programmed cell death-1 (PD-1) pathway is important in metastatic renal cell carcinoma (mRCC). However, some dissimilarities between anti-PD-1 and anti-PD-L1 inhibitors have emerged. We aimed to assess differences between anti-PD-1 and anti-PD-L1 combination immunotherapies as first-line treatments in mRCC patients.Methods: Multiple databases (PubMed, Web of Science, and Scopus) were searched for articles published until March 2021. Studies were eligible if they compared overall survival (OS), progression-free survival (PFS), objective response rates (ORR), complete response rates (CRR), and adverse events.Results: Five studies met the eligibility criteria. PD-1 combination therapy was associated with significantly better OS and PFS and higher ORR and CRR than sunitinib (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.40-0.89; HR: 0.52, 95% CI: 0.37-0.75; odds ratio [OR]: 3.20, 95% CI: 2.18-4.68; and OR: 3.05, 95% CI: 2.13-4.37, respectively; P < 0.001). For all oncological outcomes, anti-PD-1 agents were superior to anti-PD-L1 agents based on HR and OR (OS: HR = 0.88, PFS: HR = 0.76, ORR: OR = 1.85, and CRR: OR = 2.24). Conversely, anti-PD-L1 agents were superior to anti-PD-1 agents in their safety profiles. In network meta-analyses, pembrolizumab plus lenvatinib seemed the worst tolerated anti-PD-1 combination therapy.Conclusions: Our analysis indicates the superior oncologic benefits of first-line anti-PD-1 combination therapies over anti-PD-L1 combination therapies in mRCC patients. This biological difference is of vital importance for clinical treatment decision making and the design of future rational combination therapy trials in mRCC. [ABSTRACT FROM AUTHOR]

This phase 3 randomized investigation was designed to determine whether 30 months of androgen deprivation therapy (ADT) was superior to 6 months of ADT when combined with brachytherapy and external beam radiation therapy (EBRT) for localized high-risk prostate cancer. This study was conducted at 37 hospitals on men aged 40 to 79 years, with stage T2c-3a, prostate-specific antigen >20 ng/mL, or Gleason score >7, who received 6 months of ADT combined with iodine-125 brachytherapy followed by EBRT. After stratification, patients were randomly assigned to either no further treatment (short arm) or 24 months of adjuvant ADT (long arm). According to the Phoenix definition of failure, the primary endpoint was the cumulative incidence of biochemical progression. Secondary endpoints included clinical progression, metastasis, salvage treatment, disease-specific mortality, overall survival, and grade 3+ adverse events. An intention-to-treat analysis was conducted using survival estimates determined using competing risk analyses. Of 332 patients, 165 and 167 were randomly assigned to the short and long arms, respectively. The median follow-up period was 9.2 years. The cumulative incidence of biochemical progression at 7 years was 9.0% (95% CI, 5.5-14.5) and 8.0% (4.7-13.5) in the short and long arms, respectively (P =.65). The outcomes of secondary endpoints did not differ significantly between the arms. Incidence rates of endocrine- and radiation-related grade 3+ adverse events for the short versus long arms were 0.6 versus 1.8% (P =.62) and 1.2 versus 0.6% (P =.62), respectively. Both treatment arms showed similar efficacy among selected populations with high-risk features. The toxicity of the trimodal therapy was acceptable. The present investigation, designed as a superiority trial, failed to demonstrate that 30-month ADT yielded better biochemical control than 6-month ADT when combined with brachytherapy and EBRT. Therefore, a noninferiority study is warranted to obtain further evidence supporting these preliminary results. [ABSTRACT FROM AUTHOR]

• Sequential therapy with cabazitaxel improves OS in post-docetaxel mCRPC patients. • Poor PS, visceral metastasis, and symptomatic disease were prognostic factors for OS. • Pretreatment high PSA, ALP, LDH or CRP were blood-based prognostic factors for OS. • Pretreatment low hemoglobin or albumin were also blood-based prognostic factors for OS. • These findings might help guide the clinical decision-making for the use of cabazitaxel. Cabazitaxel is an effective treatment of post-docetaxel metastatic castration-resistant prostate cancer (mCRPC). We aimed to assess the sequencing impact and identify prognostic factors of oncologic outcomes in mCRPC patients treated with cabazitaxel. PUBMED, Web of Science, and Scopus databases were searched for articles published before January 2022 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they investigated pretreatment clinical or hematological prognostic factors of overall survival (OS) in mCRPC patients with progression after docetaxel treated with available treatments including cabazitaxel. Overall, 22 studies were eligible for the meta-analysis. In mCRPC patients treated with docetaxel, subsequent treatment with cabazitaxel was associated with better OS compared to that without cabazitaxel (pooled hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.56–0.89). Among the patients treated with cabazitaxel, several pretreatment clinical features and hematologic biomarkers were associated with worse OS as follows: poor performance status (PS) (pooled HR: 1.92, 95% CI: 1.33–2.77), presence of visceral metastasis (pooled HR: 2.13, 95% CI: 1.62–2.81), symptomatic disease (pooled HR: 1.47, 95% CI: 1.25–1.73), high PSA (pooled HR: 1.76, 95% CI: 1.27–2.44), high alkaline phosphatase (ALP) (pooled HR: 1.45, 95% CI: 1.28–1.65), high lactate dehydrogenase (LDH) (pooled HR: 1.54, 95% CI: 1.00–2.38), high c-reactive protein (CRP) (pooled HR: 4.40, 95% CI: 1.52–12.72), low albumin (pooled HR:1.09, 95% CI: 1.05–1.12) and low hemoglobin (pooled HR:1.55, 95% CI: 1.20–1.99). Sequential therapy with cabazitaxel significantly improves OS in post-docetaxel mCRPC patients. In mCRPC patients treated with cabazitaxel, patients with poor PS, visceral metastasis, and symptomatic disease were associated with worse OS. Further, pretreatment high PSA, ALP, LDH or CRP as well as low hemoglobin or albumin, were blood-based prognostic factors for OS. These findings might help guide the clinical decision-making for the use of cabazitaxel and prognostication of its OS benefit. [ABSTRACT FROM AUTHOR]

Background The approval of sipuleucel-T in conjunction with data from other immunotherapeutic trials for prostate cancer and other solid tumors demonstrates the potential of harnessing the patient׳s immune system for long-term survival. Thus, a range of therapeutic approaches are under evaluation. This review describes the rationale for immunotherapy for prostate cancer, summarizes the approaches under evaluation, and discusses sequencing options for immunotherapy in the current treatment paradigm. Design References for this review were identified through searches of PubMed with the search terms “prostate cancer,” “immune system,” “vaccine,” “immunotherapy,” and “T cells.” Articles were also identified through searches of the authors׳ own files. The final reference list was generated based on originality and relevance. Results The immune system can recognize and respond to prostate tumor antigens, effected through tumor-associated antigens and tumor infiltration of immune effector cells. However, evidence also suggests that prostate tumors are adept at escaping immunological recognition, thus hypothesizing multiple therapeutic strategies. Therapeutic approaches could include vaccination and modulation of T-cell function via the blockade of checkpoint receptors such as cytotoxic T-lymphocyte antigen-4 and programmed death 1. In phase III trials, sipuleucel-T improved overall survival for an M1 patient population with castration-resistant prostate cancer and ipilimumab also did so when given after radiotherapy in a subset of better risk patients. In randomized phase II trials, prostate-specific antigen-TRICOM improved overall survival and tasquinimod improved progression-free survival. Conclusion Although immunotherapy has the potential to affect advanced prostate cancer, additional research is needed to (1) identify predictive or surrogate markers of activity, (2) understand which agents are clinically effective alone or in combination with other therapies, and (3) define the optimal timing for an immunotherapy to achieve maximal benefit. [ABSTRACT FROM AUTHOR]

Purpose: To assess the differential clinical outcomes of patients treated with partial nephrectomy (PN) vs. those treated with ablation therapy (AT) such as radiofrequency ablation, cryoablation and microwave ablation for cT1b compared to cT1a renal tumors.Materials and Methods: Multiple databases were searched for articles published before August 2021. Studies were deemed eligible if they compared clinical outcomes in patients who underwent PN with those who underwent AT for cT1a and/or cT1b renal tumors.Results: Overall, 27 studies comprising 13,996 patients were eligible for this meta-analysis. In both cT1a and cT1b renal tumors, there was no significant difference in the percent decline of estimated glomerular filtration rates or in the overall/severe complication rates between PN and AT. Compared to AT, PN was associated with a lower risk of local recurrence in both patients with cT1a and cT1b tumors (cT1a: pooled risk ratio [RR]; 0.43, 95% confidence intervals [CI]; 0.28-0.66, cT1b: pooled RR; 0.41, 95%CI; 0.23-0.75). Subgroup analyses regarding the technical approach revealed no statistical difference in local recurrence rates between percutaneous AT and PN in patients with cT1a tumors (pooled RR; 0.61, 95%CI; 0.32-1.15). In cT1b, however, PN was associated with a lower risk of local recurrence (pooled RR; 0.45, 95%CI; 0.23-0.88). There was no difference in distant metastasis or cancer mortality rates between PN and AT in patients with cT1a, or cT1b tumors.Conclusions: AT has a substantially relevant disadvantage with regards to local recurrence compared to PN, particularly in cT1b renal tumors. Despite the limitations inherent to the nature of retrospective and unmatched primary cohorts, percutaneous AT could be used as a reasonable alternative treatment for well-selected patients with cT1a renal tumors. [ABSTRACT FROM AUTHOR]

The Urogenital Sub-committee and the Surveillance Committee of the Japanese Society of Chemotherapy, The Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology conducted the second nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis. In this second surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 26 hospitals and clinics from May 2016 to July 2017. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 41 isolates; the MICs (MIC 90) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, azithromycin and solithromycin were 2 μg/ml (2 μg/ml), 1 μg/ml (0.5 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.125 μg/ml (0.063 μg/ml), 0.125 μg/ml (0.125 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.031 μg/ml (0.031 μg/ml), 0.25 μg/ml (0.125 μg/ml), and 0.016 μg/ml (0.008 μg/ml), respectively. In summary, this surveillance project did not identify any strains resistant to fluoroquinolone, tetracycline, or macrolide agents in Japan. In addition, the MIC of solithromycin was favorable and lower than that of other antimicrobial agents. However, the MIC of azithromycin had a slightly higher value than that reported in the first surveillance report, though this might be within the acceptable margin of error. Therefore, the susceptibility of azithromycin, especially, should be monitored henceforth. [ABSTRACT FROM AUTHOR]

Platinum-based combination chemotherapy is the standard treatment for patients with chemotherapy-eligible metastatic urothelial carcinoma (mUC). Immune-checkpoint inhibitors (ICIs) are currently assessed in this setting. This review aimed to assess the role of ICIs alone or in combination as first-line treatment in chemotherapy-eligible patients with mUC. Multiple databases were searched for articles published until November 2020. Studies were deemed eligible if they compared overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), durations of response (DORs) and adverse events (AEs) in chemotherapy-eligible patients with mUC. Three studies met our eligibility criteria. ICI combination therapy was associated with significantly better OS and PFS, higher CRR and longer DOR than chemotherapy alone (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.76–0.94, P = 0.002; HR: 0.80, 95% CI: 0.71–0.90, P = 0.0002; odds ratio [OR]: 1.48, 95% CI: 1.12–1.96, P = 0.006; and mean difference: 1.39, 95% CI: 0.31–2.46, P = 0.01, respectively). ICI-chemotherapy combination therapy was also associated with significantly better OS and PFS, higher ORR and CRR and longer DOR than chemotherapy alone. Although OS and PFS benefits of ICI combination therapy were larger in patients with high expression of programmed death-ligand 1 (PD-L1), PD-L1 low expression patients also had a benefit; HR for OS (high PD-L1: HR 0.79 versus low PD-L1: HR 0.89) and PFS (high PD-L1: HR 0.74 versus low PD-L1: HR 0.82). ICI monotherapy was not associated with better oncological outcomes but was associated with better safety outcomes than chemotherapy alone. Our analysis indicates a superior oncologic benefit to first-line ICI combination therapies in patients with chemotherapy-eligible mUC over standard chemotherapy. In contrast, ICI monotherapy was associated with favorable safety outcomes compared with chemotherapy but failed to show its superiority over chemotherapy in oncological benefits. PD-L1 status alone cannot help guide treatment decision-making. However, caution should be exercised in interpreting the conclusions drawn from this study, given that there is the heterogeneity of the population of interest, risk of bias and the nature of the studies evaluated whose data remain immature or unpublished. • ICIs are currently assessed for patients with chemotherapy-eligible mUC. • ICIs used in combination are superior to chemotherapy in oncological benefits. • ICI monotherapy efficacy is not superior to that of chemotherapy alone. • PD-L1 alone is not a sufficiently robust, reliable and reproducible biomarker. • The analyses include the heterogeneity of the population and risk of bias. [ABSTRACT FROM AUTHOR]

Immune-checkpoint inhibitors (ICIs) are a mainstay treatment of metastatic renal cell carcinoma (mRCC). As not all patients benefit from ICIs, a biomarker-driven clinical decision-making strategy is desirable. To assess the predictive value of programmed death ligand 1 (PD-L1) in mRCC patients treated with ICIs. Multiple databases were searched for articles published up to April 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies comparing objective response rate (ORR), complete response rate (CRR), progressive disease rate (PDR), or progression-free survival (PFS) based on tumor PD-L1 status in mRCC patients were eligible. Six studies matched our eligibility criteria. Treatment with ICIs was associated with significantly higher ORRs and CRRs, and lower PDRs in patients with PD-L1–positive tumors than in those with PD-L1–negative status (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.48–2.28; OR 3.11, 95% CI 2.04–4.75; and OR 0.43, 95% CI 0.31–0.60, respectively). ICI treatment was associated with significantly better PFS in PD-L1–positive patients than in sunitinib-treated patients (hazard ratio 0.65, 95% CI 0.57–0.74), whereas this was not found in patients with PD-L1–negative tumors. Compared with sunitinib, ICI combination therapy improved ORRs and PFS significantly in PD-L1–positive patients of all examined ICIs. Nivolumab plus ipilimumab had the highest likelihood of providing the highest ORR and longest PFS in PD-L1–positive patients. PD-L1 positivity of the tumor is associated with improved ORRs and prolonged PFS in mRCC patients receiving ICI treatment and thus helps identify mRCC patients most likely to benefit from ICI treatment. The use of an immune-checkpoint inhibitor for the treatment of metastatic renal cell carcinoma (mRCC) improved oncological outcomes, and the status of programmed death ligand 1 could contribute to guiding patients and clinicians when determining personalized treatment strategies for mRCC. Patients with programmed death ligand 1–positive metastatic renal cell carcinoma show a good response to treatment with immune checkpoint inhibitors. The combination of nivolumab plus ipilimumab is highly effective in these patients. These findings could contribute to developing individualized treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review assessed compliance to guidelines for the management of nonmuscle-invasive bladder carcinoma (NMIBC).Methods: The PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched in November 2019 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis statement.Results: Fifteen studies incorporating a collective total of 10,575 NMIBC patients were eligible for inclusion in this systematic review. We found that the rates of compliance were 53.0% with a single immediate intravesical instillation in patients with presumed low or intermediate risk, 37.1% with intravesical bacillus Calmette-Guerin or chemotherapy in those with intermediate risk, 43.4% with performance of a second transurethral resection in high-risk patients, 32.5% with administration of adjuvant intravesical bacillus Calmette-Guerin in high-risk patients, 36.1% with radical cystectomy in highest-risk patients, and 82.2% with cystoscopy for follow-up.Conclusions: Compliance with NMIBC guidelines remains low. Better guideline education and understanding holds the key to achieving high compliance. Strategies to improve guideline compliance at the physician level are urgently required. [ABSTRACT FROM AUTHOR]

No standard therapy has been established for localised prostate cancer patients with prostate-specific antigen (PSA) failure after radical prostatectomy (RP). To determine whether radiotherapy ± hormone therapy is superior to hormone therapy alone in such patients. This study is a multicentre, randomised, open-label, phase 3 trial. Patients with localised prostate cancer whose PSA concentrations had decreased to <0.1 ng/ml after RP, and then increased to 0.4–1.0 ng/ml, were randomised to the salvage hormone therapy (SHT) group (80 mg bicalutamide [BCL] followed by luteinising hormone-releasing hormone agonist in case of BCL failure) or the salvage radiation therapy (SRT) ± SHT group (64.8 Gy of SRT followed by the same regimen as in the SHT group in case of SRT failure). From May 2004 to May 2011, 210 patients (105 in each arm) were registered, with the median follow-up being 5.5 yr. The primary endpoint was time to treatment failure (TTF) of BCL. TTF of BCL was significantly longer in the SRT ± SHT group (8.6 yr) than in the SHT group (5.6 yr; hazard ratio 0.56, 90% confidence interval [0.40–0.77]; one-sided p = 0.001). Thirty-two of 102 patients (31%) in the SRT ± SHT group did not have SRT treatment failure. However, clinical relapse-free survival and overall survival did not differ between the arms. The most frequent grade 3–4 adverse event was erectile dysfunction (83 patients [80%] in the SHT group vs. 76 [74%] in the SRT ± SHT group). Limitations include the short follow-up periods and surrogate endpoint setting to allow definitive conclusions. Initial SRT prolongs TTF of BCL in patients with post-RP PSA failure, indicating that SRT ± SHT is more beneficial than SHT alone. Patients who have prostate-specific antigen failure after radical prostatectomy benefit from salvage radiation therapy prior to salvage hormone therapy. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review and meta-analysis assessed the prognostic value of preoperative blood-based biomarkers in patients with upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy.Methods: PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched in June 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared cancer-specific survival in UTUC patients with and without pretreatment laboratory abnormalities. Formal meta-analyses were performed for this outcome.Results: The review identified 54 studies with 23,118 patients, of these, 52 studies with 22,513 patients were eligible for the meta-analysis. Several preoperative blood-based biomarkers were significantly associated with cancer-specific survival as follows: neutrophil-lymphocyte ratio (pooled hazard ratio [HR]: 1.66, 95% confidence interval [CI]: 1.34-2.06), C-reactive protein (pooled HR: 1.17, 95% CI: 1.07-1.29), platelet-lymphocyte ratio (pooled HR: 1.68, 95% CI: 1.30-2.17), white blood cell (pooled HR: 1.58, 95% CI: 1.02-2.46), De Ritis ratio (pooled HR: 2.40, 95% CI: 1.92-2.99), fibrinogen (pooled HR: 2.23, 95% CI: 1.86-2.68), albumin-globulin ratio (pooled HR: 3.00, 95% CI: 1.87-4.84), hemoglobin (pooled HR: 1.51, 95% CI: 1.22-1.87), and estimate glomerular filtration rate (pooled HR: 1.52, 95% CI: 1.19-1.94). The Cochrane's Q test and I2 test revealed significant heterogeneity for neutrophil-lymphocyte ratio, C-reactive protein, white blood cell, hemoglobin, and estimated glomerular filtration rate (P = 0.022; I2 = 50.7%, P = 0.000; I2 = 80.4%, P = 0.000; I2 = 88.3%, P = 0.010; I2 = 62.0%, P = 0.000; I2 = 83.9%, respectively).Conclusions: Several pretreatment laboratory abnormalities in patients with UTUC were associated with increased risks of cancer-specific mortality. Therefore, blood-based biomarkers may have the potential to serve as prognostic factors to assist patients and physicians in selecting appropriate treatment strategies for UTUC. However, considering the study limitations including heterogeneity and retrospective nature of the primary data, the conclusions should be interpreted with caution. [ABSTRACT FROM AUTHOR]

The antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using national surveillance data. The data consisted of 881 bacterial strains from eight clinically relevant species. The data were collected for the third national surveillance project from January 2015 to March 2016 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was undertaken with the cooperation of 41 medical institutions throughout Japan. Fluoroquinolone required a MIC 90 of 2–64 mg/L to inhibit the 325 Escherichia coli strains tested and the proportion of levofloxacin resistant E. coli strains increased to 38.5% from 29.6% in 2011 and 28.6% in 2008. The proportion of levofloxacin resistant strains of Pseudomonas aeruginosa and Enterococcus faecalis decreased from previous reports and the proportion of multidrug-resistant P. aeruginosa and carbapenem-resistant Enterobacteriaceae remained low. Among methicillin-resistant Staphylococcus aureus (MRSA) strains, strains with reduced susceptibility to vancomycin (minimum inhibitory concentration, 2 μg/mL) increased to 14.7% from 5.5%. Bacterial strains that produced extended-spectrum β-lactamase included E. coli (79 of 325 strains, 24.3%), Klebsiella pneumoniae (9 of 177 strains, 7.7%), and Proteus mirabilis (6 of 55 strains, 10.9%). The proportion of extended-spectrum β-lactamase producing E. coli and K. pneumoniae strains increased from previous surveillance reports. [ABSTRACT FROM AUTHOR]

Sitafloxacin (STFX) is an alternative treatment against azithromycin-resistant Mycoplasma genitalium (MG), whereas STFX-resistant MG have appeared recently. Therefore, another antimicrobial regimen for non-chlamydial non-gonococcal urethritis (NGU) is required. Garenoxacin (GRNX) is a fluoroquinolone against respiratory infections, not against urethritis in Japan, but its in-vitro antimicrobial activity against MG is known as similar to or higher than that of moxifloxacin. To clarify the efficiency of GRNX against MG, we examined the clinical efficacy of GRNX for NGU. Seventy-nine male patients with NGU were enrolled and treated with GRNX once daily for 7 days. For assessing microbiological and clinical efficacies, the bacteria including Chlamydia trachomatis (CT), MG, Mycoplasma hominis (MH), Ureaplasma urealyticum (UU) and Ureaplasma parvum (UP) were detected by means of nucleic acid amplification tests before- and after-treatment. After excluded 3 patients, seventy-six patients were evaluated: the median age; 31 (20–61) years, vaginal infection (66%); the most common infectious route and commercial sex worker (43%); the most common source. There were 50 bacteria-positive NGU cases, including 10 multiple bacterial infections. Clinical cure rate was 85.7% (36/42). Detection frequency of each bacterium was similar to the previous reported. The eradication rates of CT, MG, MH, UU and UP were 96.1%, 71.4%, 100%, 85.7% and 100%, respectively. These results indicate that GRNX has the excellent efficacies for NGU except those of MG. Further study of drug-resistant MG urethritis; for instance, studies on the clinical effectiveness of long-term such as 2-week medication of GRNX or the efficacy of alternative treatment regimens are necessary. [ABSTRACT FROM AUTHOR]

Abstract We aimed to clarify prophylactic antimicrobial effects of single-dose piperacillin (PIPC) for perioperative infections in the transurethral resection of bladder tumor (TURBT) in comparison with those of single-dose tazobactam/piperacillin (TAZ/PIPC) through a retrospective analysis. We analyzed data from 192 TURBT patients treated with single-dose (4 g) intravenous PIPC (P group) between April 2015 and April 2017. For comparison, we analyzed data from 50 TURBT patients treated with single-dose (4.5 g) intravenous TAZ/PIPC (T/P group) between June 2013 and April 2014. We compared the perioperative incidences of fever (≥38 °C) and bacteriuria in the two groups. The number of febrile patients was four (2.1%) in the P group and one (2.0%) in the T/P group, without significant difference (p = 0.970). Among these febrile patients, urine and blood samples of two patients in the P group tested positive for bacterial cultures of Citrobacter koseri and Enterococcus faecalis , respectively. None of the patients in the T/P group tested positive for urine culture, postoperatively. However, 22 patients (18.2%) in the P group tested positive for urine culture, and Staphylococcus epidermidis (six patients), E. faecalis (three patients), Escherichia coli (three patients), Streptococcus agalactiae (two patients), Staphylococcus aureus (two patients), and C. koseri (one patient) were isolated. There was no significant difference in the incidence of bacteriuria in these two groups (p = 0.055). Based on these results, single-dose PIPC administration for the prevention of perioperative infections in TURBT was as effective as TAZ/PIPC. [ABSTRACT FROM AUTHOR]

To describe the treatment-related toxicity in a multicenter randomized trial of tri-modality therapy with I-125 brachytherapy, external beam radiotherapy (EBRT), and short- or long-term androgen deprivation therapy (ADT) for high-risk localized prostate cancer (TRIP/TRIGU0907). This trial enrolled men, median age 70 years, with high-risk prostate cancer, who received three months neoadjuvant, and three months concurrent ADT combined with I-125 brachytherapy followed by EBRT. Patients were randomly assigned to either no further treatment (short arm) or 24 months of adjuvant ADT (long arm) after stratification. Primary endpoint was biochemical progression and secondary endpoints included adverse events. At clinic visits, investigators recorded toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. All analyses presented were prespecified. Radiation-related toxicity endpoints were the proportions of patients with grade 2 or worse toxicity up to 36 months. Assessments during radiotherapy were assigned to acute period; post EBRT were assigned to late period; between 12 and 33 months post EBRT were assigned to the 2-year timepoint. Other endpoints were the incidence of endocrine-related toxicity up to 36 months. The proportion of patients experiencing toxicity were compared between the arms using Fisher's exact test. A questionnaire about the usual quality of erectile (firm enough at least for foreplay or masturbation) was assessed at baseline and at five years. An intention-to-treat analysis was conducted. Of the assessable 332 patients, 165 were randomly allotted to short arm and 167 to long arm. The cumulative incidence of biochemical progression, and salvage ADT treatment were similar. There was no evidence of differences in grade 2+ radiation-related overall toxicity rates between the arms (23.6% for short vs 25.1% for long arm, p=0.799). The overall acute grade 2+ toxicity was 16.5% for genitourinary (GU) and 1.2% for gastrointestinal (GI). The overall late grade 2+ toxicity was 19.6% for GU and 4.5% for GI. The 2-year prevalence of grade 2+ toxicity was 13.0 % for GU and 3.0% for GI. No difference existed between arms for each period and prevalence. Radiation-related grade 3 GU toxicity was 0.9%, and no grade 4 GU toxicity or no grade 3 GI toxicity events were reported. The overall incidence of endocrine-related events was 37.0% for short arm, vs 46.7% for long arm (p=0.076). The incidence of hot flush was much higher in long arm (26.7% vs 40.7%, p=0.008)). The incidence of erectile dysfunction was 23.0% for short arm vs 29.3% for long arm (p=0.213). Number of patients with enough quality of erections in short vs long arm were 24 vs 30 before treatment (p=0.403), and 16 vs 8 at 5 years, respectively (p=0.076). Men with high-risk prostate cancer placed on 30 months of hormonal therapy in conjunction with combined radiation therapy had significantly more hot flushes when compared to men treated with only 6 months of ADT. Erectile function also seemed to be worse for the long arm according to the patients' reported outcomes at five years. As this investigation did not show a difference in oncologic outcomes between the two groups, a shorter course of hormone therapy should be considered given the decreased morbidity in the group. [ABSTRACT FROM AUTHOR]

Genital chlamydial infection is a principal sexually transmitted infection worldwide. Chlamydia trachomatis can cause male urethritis, acute epididymitis, cervicitis, and pelvic inflammatory disease as sexually transmitted infections. Fortunately, homotypic resistant C. trachomatis strains have not been isolated to date; however, several studies have reported the isolation of heterotypic resistant strains from patients. In this surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 51 hospitals and clinics in 2009 and 38 in 2012. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 19 isolates in 2009 and 39 in 2012. In 2009 and 2012, the MICs (MIC 90 ) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, and azithromycin were 2 μg/ml and 1 μg/ml, 0.5 μg/ml and 0.5 μg/ml, 0.125 μg/ml and 0.125 μg/ml, 0.063 μg/ml and 0.063 μg/ml, 0.125 μg/ml and 0.125 μg/ml, 0.125 μg/ml and 0.125 μg/ml, 0.016 μg/ml and 0.016 μg/ml, and 0.063 μg/ml and 0.063 μg/ml, respectively. In summary, this surveillance project did not identify any resistant strain against fluoroquinolone, tetracycline, or macrolide agents in Japan. [ABSTRACT FROM AUTHOR]

Background It is well known that the prognosis of castration-resistant prostate cancer (CRPC) is poor, and several immunotherapeutic strategies have been applied to the clinical trials. Research on immunotherapy has been of special interest for the treatment of CRPC for years. Objective To evaluate the safety of personalized peptide vaccine (PPV) immunotherapy and its clinical outcomes. Design, setting, and participants A phase 2 randomized controlled trial of PPV immunotherapy with low-dose dexamethasone versus dexamethasone alone for chemotherapy-naive CRPC began in 2008. Eligible patients (prostate-specific antigen [PSA] <10 ng/ml) were human leukocyte antigen (HLA) A02, A24, or A03 superfamily positive and had asymptomatic or minimally symptomatic CRPC. Patients were allocated (1:1) to PPV plus dexamethasone (1 mg/d) or to dexamethasone (1 mg/d) alone. A maximum of four HLA-matched peptides (each 3 mg) was selected based on the preexisting immunoglobulin G responses against the 24 warehouse peptides and administered every 2 wk. Outcome measurements and statistical analysis PSA, progression-free survival (PFS), time to initiation of chemotherapy, and overall survival (OS) were analyzed using the Kaplan-Meier method, a log-rank test, and proportional hazard analysis. Results and limitations Overall, 37 patients received peptide vaccinations and 35 received dexamethasone alone. The primary end point was PSA PFS, which was significantly longer in the vaccination group than in the dexamethasone group (22.0 vs 7.0 mo; p = 0.0076). Median OS was also significantly longer in the vaccination group (73.9 vs 34.9 mo; p = 0.00084). The relatively small number of patients enrolled is the major limitation of the study. Conclusions PPV immunotherapy was well tolerated and associated with longer PSA PFS and OS in men with chemotherapy-naive CRPC. A larger phase 3 study is needed to confirm our findings. Patient summary We compared clinical outcomes of the treatment with personalized peptide vaccine plus dexamethasone versus dexamethasone alone. Our data provide promising evidence of clinical benefit for peptide vaccines. Trial registration UMIN-CTR: 000000959. [ABSTRACT FROM AUTHOR]

To investigate antimicrobial susceptibility patterns of various bacterial pathogens isolated from complicated urinary tract infection (UTI) cases, the Japanese Society of Chemotherapy, the Japanese Association of Infectious Disease, and the Japanese Society of Clinical Microbiology conducted the second nationwide surveillance from January to September 2011. With the cooperation of 42 medical institutions throughout Japan, 1036 strains belonging to 8 clinically relevant bacterial species were collected. Among methicillin-resistant Staphylococcus aureus (MRSA) strain, the vancomycin (VCM) MIC for 5.5% (3/55) of the strains was 2 μg/mL. Ampicillin, VCM, and linezolid were relatively active against 209 Enterococcus faecalis strains. The proportion of fluoroquinolone (FQ)-resistant strains was >20%. The MIC 90 of FQs against the 382 Escherichia coli strains was 2–64 mg/L and the proportion resistant to FQs was approximately 30%. However, susceptibility of E. coli to sitafloxacin was still high (MIC 90 = 2 mg/L). Fifty-eight (15.2%) of 382 E. coli , 6 (4.5%) of 132 Klebsiella pneumoniae , 1 (2.4%) of 41 Klebsiella oxytoca and 4 (6.8%) of 59 Proteus mirabilis strains were suspected of producing extended-spectrum beta-lactamase. Of 93 Pseudomonas aeruginosa strains, the proportions resistant to imipenem, amikacin, and ciprofloxacin were 21.5%, 4.3%, and 20.4%, respectively. Four strains (4.3%) were found to be multidrug-resistant. In complicated UTI cases, all of MRSA and E. faecalis were susceptible to all anti-MRSA agents. Sitafloxacin was active against other FQ-resistant E. coli strains. The isolation of extended-spectrum beta-lactamase-producing and multidrug-resistant strains increased. [ABSTRACT FROM AUTHOR]

Degarelix is a gonadotropin-releasing hormone (GnRH) antagonist that is approved for the treatment of prostate cancer. GnRH antagonists bind directly to and block GnRH receptors, without causing the initial testosterone surge associated with GnRH agonists. A pivotal phase III study indicated that degarelix induced significantly faster reduction of testosterone and prostate-specific antigen level than GnRH agonist does. In addition, its 5-year extension trial suggested that patients could be safely switched from GnRH agonist to degarelix treatment with sustained efficacy, as measured by biochemical markers. Possible benefits of GnRH antagonists over agonists were suggested especially in patients with advanced prostate cancer with metastatic and symptomatic disease. Moreover, the recent reports including pooled data analyses on degarelix suggest improved disease control, quality of life, and lower urinary tract symptoms and decreased risk of cardiovascular diseases when compared with GnRH agonists. However, interpretation of these reports should be conducted cautiously because of the potential biases involved. This article critically reviews the results of the clinical trials and subsequent analyses and evaluates the points and counterpoints of the conclusions. [ABSTRACT FROM AUTHOR]