International Alliance of Urolithiasis (IAU) guideline on staghorn calculi management.

BACKGROUND: The stone burden based management strategy reported in the guidelines published by different associations is well known for a long time. Staghorn calculi, representing the largest burden and most complex stones, is one of the most challenging cases to practicing urologists in clinical practice. The International Alliance of Urolithiasis (IAU) has released a series of guidelines on the management of urolithiasis. PURPOSE: To develop a series of recommendations for the contemporary management management of staghorn calculi and to provide a clinical framework for urologists treating patients with these complex stones. METHODS: A comprehensive literature search for articles published in English between 01/01/1976 and 31/12/2022 in the PubMed, OVID, Embase and Medline database is performed. A series of recommendations are developed and individually graded following the review of literature and panel discussion. RESULTS: The definition, pathogenesis, pathophysiology, preoperative evaluation, intraoperative treatment strategies and procedural advice, early postoperative management, follow up and prevention of stone recurrence are summarized in the present document. CONCLUSION: A series of recommendations regarding the management of staghorn calculi, along with related commentary and supporting documentation offered in the present guideline is intended to provide a clinical framework for the practicing urologists in the management of staghorn calculi.

Validation of hyperthermia as an enhancer of chemotherapeutic efficacy: insights from a bladder cancer organoid model.

OBJECTIVE: This study aimed to evaluate the combined efficacy of hyperthermia and chemotherapy using a bladder cancer organoid model and to explore hyperthermia-related molecular pathways. METHOD: Tumor organoids were generated by embedding RT4 bladder cancer cells into Matrigel. The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Proliferation was determined by Ki67 immunofluorescence staining, and apoptosis was assessed using a TdT-mediated dUTP nick end labeling (TUNEL) assay. RNA sequencing was used to identify the differentially expressed genes. RESULTS: Bladder cancer organoids were successfully established and exhibited robust proliferative abilities. Treatment with gemcitabine or pirarubicin under hyperthermic conditions caused pronounced structural damage to the organoids and increased cell death compared to that in the normothermically treated group. Furthermore, Ki67 labeling and TUNEL assays showed that the hyperthermia chemotherapy group showed a significantly reduced proliferation rate and high level of apoptosis. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia. CONCLUSION: Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.

Revolutionizing cancer treatment: nanotechnology-enabled photodynamic therapy and immunotherapy with advanced photosensitizers.

Nanotechnology-enhanced photodynamic therapy (PDT) and immunotherapy are emerging as exciting cancer therapeutic methods with significant potential for improving patient outcomes. By combining these approaches, synergistic effects have been observed in preclinical studies, resulting in enhanced immune responses to cancer and the capacity to conquer the immunosuppressive tumor microenvironment (TME). Despite challenges such as addressing treatment limitations and developing personalized cancer treatment strategies, the integration of nanotechnology-enabled PDT and immunotherapy, along with advanced photosensitizers (PSs), represents an exciting new avenue in cancer treatment. Continued research, development, and collaboration among researchers, clinicians, and regulatory agencies are crucial for further advancements and the successful implementation of these promising therapies, ultimately benefiting cancer patients worldwide.

Apalutamide for metastatic castration-sensitive prostate cancer: final analysis of the Asian subpopulation in the TITAN trial.

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.

Partial and radical cystectomy provides equivalent oncologic outcomes in bladder cancer when combined with adequate lymph node dissection: A population-based study.

PURPOSE: To compare the oncologic outcomes of bladder cancer (BCa) patients after partial cystectomy (PC) or radical cystectomy (RC) combined with lymph node dissection (LND). METHODS: Relevant data from BCa patients who had >3 lymph nodes (LNs) removed were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Different thresholds of LN count in LND were tested to eliminate potential selection bias, and the optimal threshold was applied to screen patients who underwent adequate LND. After propensity score matching, the oncologic outcomes after PC or RC were compared in patients who underwent adequate LND. RESULTS: After preliminary screening, 6,785 BCa cases diagnosed between 2004 and 2015 with removal of > 3 LNs were enrolled in the analysis, including 633 (9.3%) PC cases and 6,152 (90.7%) RC cases. The PC and RC groups presented entirely different profiles in clinical parameters such as sex, T stage, number of lymph nodes (LNs) removed, and adjuvant therapy. In particular, the LN-positive rate and count were higher in the RC group, even after adjusting for other confounding factors. After comparison using different thresholds, the LN positive rate and count were similar when the LN count in LND was restricted to > 12. In patients who had > 12 LNs removed, after propensity score matching, PC and RC presented similar oncologic outcomes. Further exploration found that the prognosis of patients was associated with age, T stage, and the number of positive LNs. CONCLUSION: PC and RC could provide equivalent oncologic outcomes in BCa when combined with adequate LND. The conclusion needs further validation in future studies.

International Alliance of Urolithiasis Guideline on Shockwave Lithotripsy.

Different international associations have proposed their own guidelines on urolithiasis. However, the focus is primarily on an overview of the principles of urolithiasis management rather than step-by-step technical details for the procedure. The International Alliance of Urolithiasis (IAU) is releasing a series of guidelines on the management of urolithiasis. The current guideline on shockwave lithotripsy (SWL) is the third in the IAU guidelines series and provides a clinical framework for urologists and technicians performing SWL. A total of 49 recommendations are summarized and graded, covering the following aspects: indications and contraindications; preoperative patient evaluation; preoperative medication; prestenting; intraoperative analgesia or anesthesia; intraoperative position; stone localization and monitoring; machine and energy settings; intraoperative lithotripsy strategies; auxiliary therapy following SWL; evaluation of stone clearance; complications; and quality of life. The recommendations, tips, and tricks regarding SWL procedures summarized here provide important and necessary guidance for urologists along with technicians performing SWL. PATIENT SUMMARY: For kidney and urinary stones of less than 20 mm in size, shockwave lithotripsy (SWL) is an approach in which the stone is treated with shockwaves applied to the skin, without the need for surgery. Our recommendations on technical aspects of the procedure provide guidance for urologists and technicians performing SWL.

International Alliance of Urolithiasis guideline on retrograde intrarenal surgery.

OBJECTIVES: To set out the second in a series of guidelines on the treatment of urolithiasis by the International Alliance of Urolithiasis that concerns retrograde intrarenal surgery (RIRS), with the aim of providing a clinical framework for urologists performing RIRS. MATERIALS AND METHODS: After a comprehensive search of RIRS-related literature published between 1 January 1964 and 1 October 2021 from the PubMed database, systematic review and assessment were performed to inform a series of recommendations, which were graded using modified GRADE methodology. Additionally, quality of evidence was classified using a modification of the Oxford Centre for Evidence-Based Medicine Levels of Evidence system. Finally, related comments were provided. RESULTS: A total of 36 recommendations were developed and graded that covered the following topics: indications and contraindications; preoperative imaging; preoperative ureteric stenting; preoperative medications; peri-operative antibiotics; management of antithrombotic therapy; anaesthesia; patient positioning; equipment; lithotripsy; exit strategy; and complications. CONCLUSION: The series of recommendations regarding RIRS, along with the related commentary and supporting documentation, offered here should help provide safe and effective performance of RIRS.

GAS1RR, an immune-related enhancer RNA, is related to biochemical recurrence-free survival in prostate cancer.

Prostate cancer (PCa) is one of the malignant tumors of urinary system with a high morbidity. Enhancer RNA is a subclass of long non-coding RNA transcribed from active enhancer regions, which plays a critical role in gene transcriptional regulation. However, the role of enhancer RNA (eRNA) in PCa remains extremely mysterious. This study is aimed at exploring key prognostic eRNAs in PCa. First, we downloaded gene expression data and clinical data of 33 cancer types from UCSC Xena platform. Second, we selected reported putative eRNA-target pairs and performed the Kaplan-Meier survival and correlation analysis to determine the crucial eRNAs most related to biochemical recurrence (BCR)-free survival. Third, we explored the clinical characteristics with the key eRNA GAS1 adjacent regulatory RNA (GAS1RR) and performed a computational difference algorithm and the Cox regression analysis. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the underlying mechanisms. Finally, we used the pan-cancer data from The Cancer Genome Atlas (TCGA) and performed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) of 18 pairs of specimens to prove the results we acquired. Among all 2695 putative eRNAs, 6 pairs of eRNA-target genes were prominently related to BCR-free survival. Growth arrest-specific protein 1 (GAS1) was a target gene of GAS1RR (r = 0.86, P < 0.001). Patients with low GAS1RR expression were likely to have unfavorable clinical characteristics. The result of computational Cox regression analysis demonstrated that GAS1RR may predict the prognosis of PCa independently. RT-qPCR results illuminated that GAS1RR and GAS1 were both downregulated in PCa tissues, and they show a strong positive correlation. GO and KEGG analyses revealed biological processes that GAS1RR was mainly associated with. Immune infiltration analysis indicated that GAS1RR expression is correlated with the infiltration level of six kinds of immune cells. Our results suggest that GAS1RR may be clinically useful in the prediction of PCa prognosis. Moreover, it may also be a prognostic predictor and theoretic target with great promise in PCa.

International Alliance of Urolithiasis (IAU) guidelines on the metabolic evaluation and medical management of urolithiasis.

The aim of this study was to construct the fourth in a series of guidelines on the treatment of urolithiasis by the International Alliance of Urolithiasis (IAU) that by providing a clinical framework for the metabolic evaluation, prevention, and follow-up of patients with urolithiasis based on the best available published literature. All recommendations were summarized following a systematic review and assessment of the literature in the PubMed database from January 1976 to June 2022. Each generated recommendation was graded using a modified GRADE methodology. Guideline recommendations were developed that addressed the following topics: initial evaluation, metabolic testing, dietary measures, medical management, and follow-up of recurrent stone formers. It was emphasized by the Panel that prevention of new stone formation is as important as the surgical removal of the stones. Although general preventive measures may be effective in reducing stone recurrence rates in some patients, specific medical and dietary management should be well considered and eventually applied in an individualized manner based on the outcomes of metabolic work-up, stone analysis and some certain patient related factors. A detailed follow-up of each case is essential depending on the metabolic activity of each individual patient.

Corrigendum: Transcription factors BARX1 and DLX4 contribute to progression of clear cell renal cell carcinoma via promoting proliferation and epithelial-mesenchymal transition.

[This corrects the article DOI: 10.3389/fmolb.2021.626328.].

[Corrigendum] MicroRNA­10b promotes migration and invasion through KLF4 and HOXD10 in human bladder cancer.

Following the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 2 on p. 1835, which was designed to show how miR­10b promotes the migration and invasion of human bladder cancer cell lines in vitro, there appeared to be several overlapping panels such that certain of the data may have been derived from the same original sources, even though they were intended to show the results obtained under different experimental conditions. The authors have re­examined their original data, and have realized that the errors arose as a consequence of inadvertently misfiling and mishandling the data. The corrected version of Fig. 2 is shown below. Note that these errors did not affect the overall conclusions reported in the study. All the authors agree to the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish it; furthermore, they apologize for any inconvenience caused to the readership of the Journal. [the original article was published in Oncology Reports 31: 1832­1838, 2014; DOI: 10.3892/or.2014.3048].

Identification of Resolvin D1 and Protectin D1 as Potential Therapeutic Agents for Treating Kidney Stones.

Intrarenal calcium oxalate (CaOx) crystals induce renal tubular epithelial cell (TEC) inflammatory and oxidative injury. This study is aimed at exploring potential therapeutic lipid components in kidney stones because lipids are involved in the development of several diseases and indicate the risk of kidney stones. Serum specimens were collected from 35 kidney stone patients and 35 normal controls. The lipid components in serum were measured, and differences were analyzed. The documented biological importance was comprehensively reviewed to identify lipids that differed significantly between the two groups to find potential agents associated with kidney stones. CaOx nephrocalcinosis mouse model was established to examine the therapeutic effects of specific lipids on CaOx deposition and CaOx-induced oxidative renal injury. Several lipids with significantly different levels were present in the serum of patients with stones and normal controls. Resolvin D1 (RvD1) (4.93-fold change, P < 0.001) and protectin D1 (PD1) (5.06-fold change, P < 0.001) were significantly decreased in the serum of patients with kidney stones, and an integrative review suggested that these factors might be associated with inflammatory responses, which is a crucial mechanism associated with stone damage. The administration of RvD1 and PD1 significantly inhibited kidney CaOx deposition and suppressed CaOx-induced renal tubular cell inflammatory injury and necrosis in a CaOx nephrocalcinosis mouse model. Furthermore, RvD1 and PD1 facilitated the expression of the oxidative indicator superoxide dismutase 2 (SOD2), inhibited NADPH oxidase 2 (NOX2) expression, and diminished intracellular reactive oxygen species (ROS) levels. This study preliminarily elucidated the role of lipids in kidney stones. The inhibitory effects of RvD1 and PD1 on oxidative damage induced by CaOx deposition provide a promising perspective for kidney stone treatment strategies.

Erratum: Inhibition of SMYD2 suppresses tumor progression by down-regulating microRNA-125b and attenuates multi-drug resistance in renal cell carcinoma: Erratum.

[This corrects the article DOI: 10.7150/thno.37628.].

Erratum: Sulforaphane elicts dual therapeutic effects on Renal Inflammatory Injury and crystal deposition in Calcium Oxalate Nephrocalcinosis: Erratum.

[This corrects the article DOI: 10.7150/thno.44054.].

European Association of Urology Section of Urolithiasis and International Alliance of Urolithiasis Joint Consensus on Percutaneous Nephrolithotomy.

CONTEXT: Although percutaneous nephrolithotomy (PCNL) has been performed for decades and has gone through many refinements, there are still concerns regarding its more widespread utilization because of the long learning curve and the potential risk of severe complications. Many technical details are not included in the guidelines because of their nature and research protocol. OBJECTIVE: To achieve an expert consensus viewpoint on PCNL indications, preoperative patient preparation, surgical strategy, management and prevention of severe complications, postoperative management, and follow-up. EVIDENCE ACQUISITION: An international panel of experts from the Urolithiasis Section of the European Association of Urology, International Alliance of Urolithiasis, and other urology associations was enrolled, and a prospectively conducted study, incorporating literature review, discussion on research gaps (RGs), and questionnaires and following data analysis, was performed to reach a consensus on PCNL. EVIDENCE SYNTHESIS: The expert panel consisted of 36 specialists in PCNL from 20 countries all around the world. A consensus on PCNL was developed. The expert panel was not as large as expected, and the discussion on RGs did not bring in more supportive evidence in the present consensus. CONCLUSIONS: Adequate preoperative preparation, especially elimination of urinary tract infection prior to PCNL, accurate puncture with guidance of fluoroscopy and/or ultrasonography or a combination, keeping a low intrarenal pressure, and shortening of operation time during PCNL are important technical requirements to ensure safety and efficiency in PCNL. PATIENT SUMMARY: Percutaneous nephrolithotomy (PCNL) has been a well-established procedure for the management of upper urinary tract stones. However, according to an expert panel consensus, core technical aspects, as well as the urologist's experience, are critical to the safety and effectiveness of PCNL.