OBJECTIVE:To evaluate the feasibility and preliminary perioperative outcomes of a traction pre-bladder suturing technique for managing the intramural ureter during single-position robot-assisted laparoscopic nephroureterectomy (RALNU) in patients with early-stage upper tract urothelial carcinoma (UTUC). METHODS:10 consecutive patients with early-stage UTUC underwent RALNU (Oct 2022-Aug 2023). The technique involves four steps: mucosal tenting, a purse-string suture for containment, en bloc resection of the protruding mucosa and ureter, and reinforced double-layer bladder closure. RESULTS:All procedures were successful. Mean operative time was 145 min, with 38 min dedicated to the intramural segment. Mean blood loss was 35 mL, with no conversions or major complications. Pathology confirmed R0 resection of low-grade noninvasive carcinoma. Two metachronous bladder recurrences occurred during a median 12-month follow-up. CONCLUSION:This technique appears to be a feasible approach in patients with early-stage UTUC, with the potential to minimise urine spillage and facilitate secure bladder closure during RALNU.

Rationale and Objectives To investigate the clinical significance of Di Distance, defined as the projected craniocaudal distance along the inferior vena cava (IVC) between the confluence levels of the left and right renal veins, in patients with Nutcracker Syndrome (NCS) and its potential role in disease pathogenesis. Materials and Methods In this retrospective study from January 2022 to January 2026, 46 patients with NCS confirmed by renal venography and 55 control participants who underwent abdominal CTA/CTV and renal venography but had negative venographic findings, defined as an LRV-IVC pressure gradient of <3 mmHg, were included. Conventional imaging parameters and Di Distance were compared between NCS patients and controls. Diagnostic performance was assessed using ROC analysis. Results Di Distance was significantly larger in patients with NCS than in controls. Incorporating Di Distance improved the diagnostic performance of conventional imaging parameters. These findings suggest that Di Distance may serve as an additional anatomical marker associated with Left renal vein (LRV) compression. Conclusion Di Distance was significantly increased in patients with NCS and may serve as a supplementary anatomical parameter associated with LRV compression. Incorporating Di Distance may improve the diagnostic performance of conventional imaging indicators. These findings suggest a potential anatomical explanation for NCS patients with relatively normal aortomesenteric angles, but further prospective studies integrating hemodynamic validation are required.

BACKGROUND:This study compares outcomes of robotic Robotic-assisted left renal vein (LRV) transposition with and without proximal left gonadal vein (LGV) transposition for Nutcracker Syndrome (NCS). METHODS:A retrospective analysis was conducted on 24 NCS patients. Group A (n = 13) had LRV transposition. Group B (n = 11) had combined LRV+ proximal LGV transposition. Outcomes including operative details, complications, symptom resolution, and renocaval pressure gradient (RPG) reduction. RESULTS:Operative time and hospital stay were similar between the groups. However, group B had a higher lymphatic leakage rate (64% vs. 8%; p = 0.0078) and required longer drainage (median 5 vs. 3 days; p = 0.02). Clinical symptoms improved in both groups. Group B achieved substantially greater RPG reduction (70% ± 15% vs. 55% ± 8%; p = 0.004). CONCLUSIONS:Robotic LRV and proximal LGV transposition for significant dilation is safe and effective. Despite higher short-term lymphatic morbidity, the combined approach offers greater reduction in RPG, providing a valuable alternative for selected patients. TRIAL REGISTRATION:This research was also registered at the Chinese Clinical Trial Registry. The registration number is ChiCTR2500099335 (Link: https://www.chictr.org.cn/bin/project/edit?pid=261879).

Chronic allograft rejection (CAR) is characterized by progressive fibrosis and remains a major cause of long-term graft failure after transplantation. Here, we investigated the contribution of recipient TLR9 signaling to macrophage-associated fibrotic remodeling in CAR and evaluated pharmacological modulation of this pathway. Using murine heterotopic heart transplantation models of acute and chronic rejection, combined with single-cell RNA sequencing, global TLR9-deficient recipients, and primary cell co-culture systems, we found that macrophages with high TLR9 pathway activity were enriched in the chronic rejection microenvironment. Although TLR9 deficiency did not significantly affect acute rejection survival, it markedly reduced collagen deposition, vascular remodeling features visible on H&E staining, and prolonged graft survival in chronic rejection. Mechanistically, TLR9 activation was associated with macrophage-to-myofibroblast transition via the TGF-β1/Smad3 axis and enhanced IL-6 secretion, which activated resident fibroblasts through Stat3 signaling in a paracrine manner. Hydroxychloroquine (HCQ), an endolysosomal immunomodulatory agent that can interfere with nucleic-acid sensing pathways including endosomal TLR signaling, suppressed macrophage transition and fibroblast activation, attenuated graft fibrosis, and improved survival in vivo. These findings identify recipient TLR9 signaling as an important regulator of macrophage-associated chronic cardiac allograft fibrotic remodeling and support further investigation of this pathway as a therapeutic target.

Background:Nutcracker syndrome (NCS) diagnosis remains challenging due to the lack of non-invasive, reliable methods. Current techniques, including Doppler ultrasound and computed tomography angiography (CTA), lack hemodynamic data, with invasive measurement of the left renal vein-inferior vena cava (LRV-IVC) pressure gradient (true pressure gradient, TPG) being the gold standard. This study aimed to validate a novel non-invasive approach using finite element analysis (FEA) to simulate the LRV-IVC pressure gradient (SPG) to assist in diagnosing and monitoring NCS. Methods:This retrospective study included 46 patients (35 NCS, 11 controls) who underwent CTA and invasive TPG measurement. Patient-specific 3D left renal vein (LRV) models were reconstructed from CTA data using MIMICS and 3-matic software. Hemodynamic simulations were performed via ANSYS (an engineering simulation software) to calculate SPG. Diagnostic performance of SPG and imaging parameters (e.g., beak sign, LRV diameter ratio) was evaluated using receiver operating characteristic (ROC) analysis. Results:SPG showed no significant difference from TPG (5.6±3.9 vs. 5.5±1.9 mmHg, P>0.05) in NCS patients. Postoperative SPG and TPG decreased comparably (P<0.05). SPG achieved an area under the curve (AUC) of 0.808 [95% confidence interval (CI): 0.69-0.92] with 81.8% sensitivity and 80.0% specificity at a cutoff of 3.3 mmHg, outperforming traditional imaging markers. The aortomesenteric angle, LRV diameter ratio, and beak sign also demonstrated diagnostic utility. Conclusions:FEA-derived SPG correlates closely with invasive TPG, offering a reliable, non-invasive alternative for NCS diagnosis and postoperative monitoring. This approach enhances objectivity, reduces reliance on operator-dependent techniques, and may facilitate early intervention. Further refinement of FEA models and multicenter validation are warranted.

Prostate cancer (PCa) remains a significant clinical challenge, particularly in localized therapy, where unmet medical needs persist for effective and targeted treatments. This study introduces an innovative solution by developing the first responsive spermine (Spm) hydrogel with an autonomous sensing function, designed to advance local therapy for PCa. Our hydrogel effectively loads Spm and releases Spm in the acidic tumor microenvironment (TME), providing a responsive therapeutic platform. Incorporating the di-lysine-7-nitrobenzofurazan (NBD-KK) dye, which is initially quenched by aggregate formation within the hydrogel, the release of Spm can be monitored in real time. With its autonomous sensing capability within the tumor, re-administration of the hydrogel can be determined based on real-time monitoring of Spm release. Notably, in vivo results indicate a safe and effective dosage of 0.53 mg of Spm in the hydrogel for prostate tumor inhibition. This novel approach holds promise for enhancing local therapy in PCa and improving the quality of life for patients.

Castration-resistant prostate cancer (CRPC) remains lethal due to adaptive resistance mechanisms such as stress-induced autophagy and NF-κB survival signaling. Here, an injectable fiber-in-hydrogel depot is developed for sequential delivery of a multi-enzyme nanozyme (cobalt-epigallocatechin gallate coordination nanozyme, CoNZ) and the lysosomal inhibitor chloroquine (CQ). The preferentially released CoNZ catalytically generates reactive oxygen species, including hydroxyl radicals, and oxygen in situ, inflicting oxidative damage while relieving tumor hypoxia. Simultaneously, it depletes antioxidants (glutathione, NADPH) and impedes NF-κB nuclear translocation, priming CRPC cells for apoptosis. The subsequently released CQ impedes enzymatic degradation or cleavage in endolysosomes and autolysosomes and blocks TLR9/NF-κB signaling, preventing tumor cells from repairing damage or activating pro-survival pathways. In vitro and in vivo, this two-pronged approach synergistically overcomes CRPC's defenses, achieving markedly enhanced cancer cell apoptosis and ∼80% tumor suppression (with occasional complete regression), resulting in an approximately 10-fold reduction in final tumor volume compared to the untreated control, without systemic toxicity, far surpassing single or co-administered treatments. This work demonstrates a spatiotemporally orchestrated combination of nanocatalytic therapy and lysosomal inhibition that dismantles CRPC's resistance mechanisms, highlighting a broadly applicable paradigm for overcoming therapeutic resistance in aggressive cancers.

The grading classification of clear cell renal cell carcinoma (CCRCC) is a crucial prognostic factor. However, manual observation can lead to subjective and inconsistent diagnoses. In this study, we aimed to develop a deep-learning-based grading system for CCRCC using whole-slide image (WSI) and to predict disease progression. A total of 305 CCRCC cases were used to develop the renal cell carcinoma artificial intelligence diagnosis (RCCAID) model for grading (188 training, 47 verification, and 70 testing cases) and the renal cell carcinoma artificial intelligence prognostic (RCCAIP) progression prediction model (288 cases). Progression was defined as the presence of distant and/or lymph node metastasis. Xception, ResNet50, and Inception V3 were employed. Model performance was assessed via confusion matrix, receiver operator characteristic curve (ROC) curve, and classification map. RCCAID achieved area under the curve (AUC) values of 0.987 (internal), 0.996 (in-house), and 0.967 (external). The quadratic weighted Cohen’s kappa was 0.864, comparable to senior pathologists (0.871). RCCAIP achieved an AUC of 0.94 for progression prediction. Higher grades correlated with worse prognosis. RCCAID can accurately grade CCRCC in whole-slide images, and RCCAIP is effective in progression prediction, even for low-grade tumors.

Renal cell carcinoma (RCC) is highly vascular and prone to venous invasion and tumor thrombus (TT) formation, though its underlying molecular mechanisms remain unclear. In this study, we found suprabasin (SBSN) was upregulated in RCC and enriched in TT, associated with poor prognosis. SBSN promoted RCC cell proliferation, migration, and invasion via the NF-κB-CD44 axis, and its knockdown inhibited tumor growth and affected epithelial-mesenchymal transition in vivo. Clinically, SBSN expression in RCC tissue positively correlates with microvessel density. Mechanistically, SBSN drove angiogenesis paracrinally by upregulating interferon alpha-inducible protein 6 (IFI6) in endothelial cells, which in turn inhibits endothelial cell apoptosis and promotes tube formation. Collectively, SBSN acts both intrinsically (NF-κB-CD44 axis) to boost tumor aggressiveness and extrinsically (SBSN-IFI6 axis) to promote angiogenesis. This study positions SBSN as a potential prognostic biomarker and therapeutic target to disrupt both tumor growth and vascular support in advanced RCC.

e17103 Background: Apalutamide (APA) combined with androgen deprivation therapy (ADT) is the standard care for mHSPC and is associated with significant survival benefits. Given limited data from Chinese patients (pts), this study aimed to conduct the largest observational investigation to date to assess the real-world effectiveness and safety of APA plus ADT in Chinese pts with mHSPC, with a focus on prostate-specific antigen (PSA) decline and disease progression. Methods: This retrospective, multicenter observational study enrolled adult pts with mHSPC who initiated on APA plus ADT between 1 Jan 2022 and 31 May 2024 (index date), with follow-up through 31 May 2025, utilizing data from chart review. The observation period for each pt spanned from the index date to loss to follow-up, death, or 1-year follow-up. The primary endpoint was the proportion of pts achieving PSA≤0.2 ng/mL (PSA0.2) at Month (M) 3. Other endpoints included proportion of pts achieving a decrease in PSA ≥50% or ≥90% (PSA50/90), PSA progression, clinical and radiographic disease progression events within 12 mo. The number and proportion of pts achieving PSA0.2 or PSA50/90 along with their 95% confidence intervals (CIs) were determined by using Clopper–Pears on exact method on the basis of observed case data. Subgroup analyses were performed by age ( < 65, ≥65 to < 75, and ≥75 yr) and Gleason score (≤7 or > 7) on PSA0.2. Adverse drug reactions (ADRs) were collected for safety evaluation. Results: There were 300 pts with mHSPC treated with APA plus ADT analyzed. Median treatment duration was 12.8 (range 0.1–13.5) mo. Baseline characteristics were as follows: median age 72 (range 40–97) yr, Gleason score > 7 in 84% (172/204) of pts, tumor stage T3 in 22/84 and T4 in 51/84 pts, median PSA100 (range 0.1–5000) ng/mL. PSA0.2 response was 41.1% at M3, increasing to 62% at M6 and 69.7% at M12. PSA50 and PSA90 responses were 98.8% and 92% at M3, respectively. PSA progression (increase ≥50% and ≥5 ng/mL above nadir) occurred in 7 pts; clinical and radiographic disease progression occurred in 2 pts and 1 pt. Regarding safety analysis, ADRs were reported in 13% of pts, with ADRs (grade 3–4) reported in 1%. 4 deaths were reported. PSA0.2 response did not show meaningful difference across subgroups. Conclusions: The CAPABLE, the largest published APA real-world study in China, reveals a notably high PSA response for APA plus ADT, with infrequent progression reported, indicating a favorable prognosis for pts with mHSPC. The regimen also has a tolerable safety profile. PSA response among pts with mHSPC after APA plus ADT treatment. % (n/N) 95% CI PSA0.2M3M6M12 41.1% (76/185)62% (98/158)69.7% (99/142) 33.9%–48.5%54%–69.6%61.5%–77.1% PSA50M3M6M12 98.8% (160/162)97.1% (134/138)95.3% (121/127) 95.6%–99.9%92.7%–99.2%90%–98.2% PSA90M3M6M12 92% (149/162)91.3% (126/138)92.9% (118/127) 86.7%–95.7%85.3%–95.4%87%–96.7%

The diagnostic rate of prostate cancer (PCa) remains suboptimal, particularly for patients whose serum prostate-specific antigen (PSA) concentration is less than 10 ng/mL. Single-cell sequencing, machine learning, and Mendelian randomization have emerged in recent years as excellent methods for identifying tumour markers. We identified 3 genes (RAB3B, SPON2, and SLC4A4) through single-cell sequencing and a machine learning screen. Among them, RAB3B (Ras-related protein, Rab-3B) had a higher area under the diagnostic curve for PSA < 10 ng/mL PCa (0.763) than the other two genes did. Mendelian randomization analysis revealed that the occurrence of PCa led to an increase in circulating levels of the RAB3B protein. Western blot and immunohistochemical analyses demonstrated that RAB3B was overexpressed in PCa tumour. Subsequently, elevated levels of RAB3B were detected in the culture medium of PCa cells. Furthermore, urinary RAB3B protein levels were significantly increased in PCa patients. For patients with PSA levels < 10 ng/mL, urinary RAB3B exhibited an area under the receiver operating characteristic curve (AUC) of 0.733 for PCa diagnosis, outperforming both PSA concentration (AUC = 0.682) and age (AUC = 0.651). Notably, the AUC of the multivariate model urine RAB3B + PSA + Age is 0.8. GSEA at al analysis and functional experiments, including gain-of-function and loss-of-function studies revealed that RAB3B promotes the proliferation and migration of PCa cells. In summary, urinary RAB3B, discovered through a multiomics approach, is a promising biomarker that is complementary to serum PSA, and together these factors can improve diagnostic decision-making in the PSA grey zone.

OBJECTIVE:To evaluate the feasibility of a novel robotic-assisted laparoscopic technique-side clamp two-step vascular method-for left renal vein (LRV) transposition in nutcracker syndrome (NCS). METHODS:Between May and December 2023, three male NCS patients (median age: 14 years) underwent robot-assisted LRV transposition using the Di's technique. The key procedure included a side clamp two-step technique to selectively occlude the infrarenal inferior vena cava and LRV without right renal vein manipulation. Surgical outcomes, including operative time, blood loss, anastomosis duration, and postoperative complications, were retrospectively analysed. RESULTS:All procedures were successfully completed. Median operative time was 125 min, with LRV anastomosis completed in 23 min. Postoperative imaging confirmed the resolution of LRV compression, with pressure gradients reduced to < 3 mmHg. Symptoms resolved completely within 4 weeks. CONCLUSIONS:The robotic-assisted side clamp two-step technique offers a minimally invasive alternative for LRV transposition in NCS, minimising vascular dissection and preserving right renal venous flow. TRIAL REGISTRATION:This clinical trial has been registered in the Chinese Clinical Trial Registry (ChiCTR, registration number: ChiCTR2500099335).

This study aimed to investigate the value of integrating computed tomography (CT)-based tumor radiomics features with clinical parameters for preoperative prediction of microvascular invasion (MVI) in clear cell renal cell carcinoma (ccRCC). We retrospectively analyzed data from a single-center cohort of ccRCC patients. Radiomics features were extracted from preoperative multiphasic CT scans (unenhanced, corticomedullary, and nephrographic phases). Following dimensionality reduction and feature selection, eight machine learning algorithms were evaluated to identify the optimal radiomics model. Independent clinical predictors were determined through univariate and multivariate analyses. A nomogram integrating the radiomics signature (rad-score) with significant clinical parameters was subsequently developed. Model performance was assessed using the area under the curve (AUC), decision curve analysis (DCA), and calibration curve analysis (CAC). Of 143 initially enrolled patients, 110 met inclusion criteria after screening, with 5502 radiomics features extracted. The support vector classifier (SVM) model demonstrated the highest discriminative ability, achieving mean AUCs of 0.976 (training cohort) and 0.892 (test cohort), significantly outperforming the clinical model (training AUC = 0.935, test AUC = 0.933). The nomogram showed superior diagnostic performance, with AUCs of 0.958 (test). DCA and CAC confirmed its clinical utility and robustness. Multiparametric CT radiomics models enable non-invasive prediction of MVI status in ccRCC, with the SVM-based algorithm showing optimal performance. The integrated nomogram provides excellent and consistent diagnostic accuracy, offering a valuable preoperative tool for clinical decision-making.

No non-invasive biomarkers are clinically available to distinguish aggressive prostate cancer (PCa) from the indolent PCa, as thus may lead the misdiagnose and overtreatment to the patients. This study aims to identify secreted proteins and assess their potentials to discriminate two PCa subtypes. Microarray assay on tissue specimens of the discovery cohort identified secreted genes associated with invasive PCa and macrophage polarization, and the results were validated in an independent cohort. As elevated expression of ΔC499 has been linked to metastatic PCa and poorer prognosis, the relationship of key secretory genes and ΔC499 was investigated. Their roles on macrophage polarization were studied in co-cultured cells, PCa mouse model and patient blood samples. Finally, a multi-gene secreted signature model was developed and tested in training and validation cohorts. ITGB5 was upregulated and TIMP1/TMEM176B were downregulated at RNA level in aggressive Pca, with bioinformatics linking these changes to M2 macrophage polarization. Additionally, we found that ITGB5 expression was positively regulated while TIMP1 and TMEM176B were negatively regulated through distinct transcriptional pathways. Further, we revealed that ΔC499 contributes to ITGB5-driven M2 macrophage polarization, enhancing PCa invasion in vitro and in vivo. Lastly, a multi-gene model integrating ITGB5, TIMP1, and TMEM176B distinguished indolent from aggressive PCa in training cohort (AUC = 0.88) and validation cohort (AUC = 0.90). ΔC499 induces M2 macrophage polarization and drives PCa invasiveness by modulating ITGB5, TIMP1, and TMEM176B. Three genes signature is differentially expressed between aggressive and indolent tumors, providing potential non-invasive biomarkers to discriminate aggressive from indolent PCa.

OBJECTIVE:To evaluate the feasibility and outcomes of a novel robotic-assisted laparoscopic technique-Di's II robotic-assisted left renal vein (LRV) transposition with distal gonadal vein (GV) anastomosis-creating dual venous drainage for treating nutcracker syndrome (NCS). METHODS:Between December 2023 and October 2024, three male patients (median age, 14 years) with NCS underwent robotic-assisted LRV transposition using the Di's II technique. Key procedural innovations included selective occlusion of the infrarenal inferior vena cava (IVC) and LRV without right renal vein clamping, combined with distal GV anastomosis to enhance venous drainage. Operative parameters, including anastomosis time, blood loss, and postoperative outcomes, were analyzed retrospectively. RESULTS:All procedures were successfully completed robotically. Median total operative time was 145 minutes (range, 135-160 minutes), with LRV and GV anastomosis times of 25 minutes (range, 24-27 minutes). The median estimated blood loss was 40 mL (range, 30-50 mL). Postoperative imaging confirmed resolution of LRV compression, with pressure gradients reduced to ≤2.8 mm Hg. Symptoms (hematuria, proteinuria, and varicocele) resolved within 6 months, and no perioperative complications occurred during follow-up. CONCLUSIONS:The Di's II technique represents a safe and effective minimally invasive approach for NCS, combining robotic precision with dual venous drainage to alleviate LRV hypertension and pelvic congestion. Preliminary outcomes demonstrate technical feasibility, a lower ischemia risk, and symptom resolution, supporting further validation in larger cohorts.

BackgroundThis retrospective cohort study and meta-analysis aims to explore the association between microvascular invasion (MVI) and clinicopathologiccal features, as well as survival outcomes of patients with renal cell carcinoma (RCC).Material and methodsThe retrospective cohort study included 30 RCC patients with positive MVI and another 75 patients with negative MVI as controls. Clinicopathological features and follow-up data were compiled. The meta-analysis conducted searches on PubMed, Cochrane Library, Web of Science, Embase, and WanFang Data from the beginning to 30 September 2023, for comparative studies relevant to MVI patients. The Newcastle-Ottawa Scale and Egger Test were used to assess the risk of biases and certainty of evidence in the included studies.ResultsThe cohort study showed that MVI was associated with advanced primary tumor stage, high pathological grades, high tumor size, high clinical symptoms and lymph node invasion (P <0.05). Kaplan-Meier analyses demonstrated MVI was associated with worse CSS rates when compared to MVI negative group (P <0.05). However, in the multivariate analysis it was not presented as an independent predictor of cancer survival mortality (P >0.05). The meta-analysis part included 11 cohort studies. The results confirmed that patients with MVI positive had worse 12 and 60 mo CSS rates (HR12mo = 0.86, 95%CI 0.80–0.92; HR60mo = 0.63, 95% CI 0.55–0.72; P < 0.00001). Moreover, the meta-analysis also confirmed that MVI group was associated with higher rate of advanced tumor stage, pathological grades, tumor size diameter, higher rate of clinical symptoms and lymph node invasion (P <0.05).ConclusionsThe presence of MVI in renal cell carcinoma patients is linked to poorer survival outcomes and worse clinicopathological features. In spite of this, it does not seem to be an independent predictor for cancer survival mortality in renal cell carcinoma.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023470640, identifier CRD42023470640.

Objectives: To identify the cooperation of authors, countries, institutions and explore the hot spots regarding research of renal cell carcinoma with venous tumor thrombus. Methods: Relevant articles were obtained from the Web of Science Core database (WoSC) from 1999 to 2024. CiteSpace was used to perform the analysis and visualization of scientific productivity and emerging trends. Network maps were generated to evaluate the collaborations between different authors, countries, institutions, and keywords. Results: A total of 2180 related articles were identified. We observed an increased enthusiasm in related fields during the past two decades. The USA dominated the field in all countries, and the University of Miami was the core institution. Ciancio G might have a significant influence with more publications and co-citations. Current research hotspots in this field mainly included thrombectomy, tyrosine kinase inhibitors, immune checkpoint inhibitors, vena cava inferior, and microvascular invasion. Thrombectomy complications, thrombectomy survival outcome, and preoperative neoadjuvant immunotherapy represented the frontiers of research in this field, undergoing an explosive phase. Conclusion: This is the first bibliometric study that comprehensively visualize the research trends and status of RCC with VTT. We hope that this work will provide new ideas for advancing the scientific research and clinical application.

Metastatic prostate cancer (PCa) remains incurable and causes considerably diminished overall survival. Despite significant progress in pharmacotherapy, the disease prognosis remains unchanged. Immune checkpoint inhibitors (ICIs) have demonstrated effectiveness in treating various advanced malignancies, but their efficacy in metastatic PCa is relatively limited. Previous studies have confirmed the immunosuppressive role of tumor-infiltrating B cells (TIL-Bs) in the PCa microenvironment, which accounts for their poor immunogenic potency. In this study, we demonstrated that an oral kinase agent, ibrutinib, strongly potentiated anti-PD-1 checkpoint blockade efficacy and successfully controlled tumor growth in a murine orthotopic PCa model constructed using a metastatic and hormone-independent cell line (RM-1). We identified close relationships between TIL-Bs, Bruton's tyrosine kinase (BTK), and immunosuppressive molecules by bioinformatics and histological analysis. An in vitro study showed that a low dose of ibrutinib significantly inhibited B cell proliferation and activation as well as IL-10 production through the BTK pathway. Moreover, ibrutinib-treated B cells promoted CD8+ T cell proliferation and inhibitory receptor (IR) expression. However, the same dose of ibrutinib was insufficient to induce apoptosis in cancer cells. An in vivo study showed that ibrutinib monotherapy failed to achieve tumor regression in murine models but decreased B cell infiltration and inhibited activation and IL-10 production. More importantly, CD8+ T cell infiltration increased with high IR expression. Ibrutinib synergized with anti-PD-1 checkpoint blockade enormously improved antitumor immunity, thereby reducing tumor volume in the same scenario. These data set the scene for the clinical development of ibrutinib as an immunogenic trigger to potentiate anti-PD-1 checkpoint blockade for metastatic PCa immunotherapy.

Background: The aim of the study was to identify the cooperation of authors, countries, institutions and explore the hot spots regarding research of tyrosine kinase inhibitors (TKIs) for renal cell carcinoma (RCC) treatment in the past 22 years. Summary: Relevant original and review articles were obtained from the Web of Science Core Collection from 2000 to 2022. CiteSpace software was used to perform the visualization of scientific productivity and emerging trends. Network maps were generated to evaluate the collaborations between different authors, countries, institutions, and keywords. Key Messages: A total of 4,951 articles related to TKI for RCC treatment were identified. We observed a gradual increase in the number of publications from 2000 to 2022. The USA dominated the field in all countries, and Mem Sloan Kettering Cancer Centre (USA) had more extensive cooperating relationships with other institutions. Motzer RJ and Escudier B were two of the authority scholars in this specific field with the most publications and co-citations. Journal of Clinical Oncology had the most citations of all the journals. A total of 10 major clusters were explored based on the reference co-citation analysis. From 2000 to 2022, the research hot spots have undergone two dramatic shifts during 2006 and 2019, respectively, relevant topics were TKI and TKI combined with immune checkpoint inhibitors (CPIs). At present, the research hot spots focus on CPI and targeted therapies. Bibliometric analysis is allowing researchers to recognize the current research status by providing a comprehensive overview of the development of scientific literature related to TKI for RCC treatment, and information for further research be demonstrated as well.

Objective:To explore the technical essentials of robot-assisted radical prostatectomy via posterior and completely intrafascial for organ-confined prostate cancer, and to evaluate the oncological and functional outcomes.Methods:Fifteen prostate cancer patients with T1-2bN0M0 were scheduled for robot-assisted radical prostatectomy via posterior and completely intrafascial approach, and their international index of erectile function (IIEF) were performed before operation. All patient was placed in a supine position and the robotic system was established. Firstly, expose the Douglas fossa, free bilateral vas deferens and seminal vesicles, blunt dissection of the Denonvillier fascia, severed lateral ligament and visceral pelvic fascia, then exposed and disconnected urethra, continuous suture bladder neck urethra. Perioperative complications and functional outcome data were recorded. All patients were regularly followed up for tPSA testing, daily urine pads and IIEF-5 scores.Results:All of the 15 patients were successfully completed the operations. The median (range) operation time was 86(65-116) min, and estimated blood loss was 20 (10-60) ml, and no serious complications occurred. Postoperative pathology was 18.Conclusions:Robot-assisted radical prostatectomy via posterior and completely intrafascial approach is technically feasible for patients with low-risk localized prostate cancer and demonstrates promising functional outcomes regarding continence and potency.