Relationships of dietary habits with prostate cancer risk: results from Mendelian randomization analyses and the National Health and Nutrition Examination Survey.

Background: Prior investigations identified correlations between dietary habits and the risk of prostate cancer (PCa); however, the causative dynamics are unclear. Methods: Utilizing the Mendelian randomization (MR) framework, we investigated the causal links between dietary habits, daily nutrient intakes, and risk of PCa (79 148 cases and 61 106 controls). Exposure and outcome data were obtained from the UK Biobank and the Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome (PRACTICAL) consortium, respectively. Univariable and multivariable MR analyses were employed. Sensitivity analyses were performed to detect outliers, evaluate heterogeneity, and discern potential pleiotropic effects. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) database (2009-2010), we selected 1294 and 1778 men aged ≥40 years from a pool of 10 537 participants, ensuring no missing information. Regression analyses examined the associations between leafy/lettuce salad intake, daily nutrient intake, and the odds of PCa. Results: Univariable MR (UVMR) analysis reveals that the intake of pork and salad/raw vegetable correlated with an elevated PCa risk. Subsequent to confounder adjustment via multivariable MR (MVMR) analysis, a causal link was established between salad/raw vegetable intake and an increased risk of PCa (odds ratio [OR]: 1.658, 95% confidence interval [95% CI]: 1.037-2.644, P = 0.046). The analysis based on NHANES datasets demonstrated a link between leafy/lettuce salad intake and heightened odds of PCa (OR: 1.025, 95% CI: 1.003-1.049, P = 0.038). Increased daily intakes of ß-carotene (original OR: 1.00006, 95% CI: 1.00001-1.00011, P = 0.024) and vitamin B1 (OR: 1.474, 95% CI: 1.104-1.967, P = 0.014) were associated with a higher likelihood of PCa. Conclusions: These MR analyses substantiate the causal nexus between salad/raw vegetable intake and PCa risk. Similarly, leafy/lettuce salad intake and the odds of PCa were significantly correlated in the cross-sectional observational study. Moreover, higher daily intakes of ß-carotene and vitamin B1 were linked to an increased likelihood of PCa. These findings provide practical dietary recommendations for PCa prevention and enhance early identification and diagnosis.

Cognitive interviewing validation of the Chinese version of the neurogenic bladder symptom score.

Background: The neurogenic bladder symptom score (NBSS) has been widely used to specifically measure symptoms and consequences of neurogenic bladder (NB). The cognitive interviewing (CI) is effective in assessing item clarity and identifying key issues related to the comprehension of the instrument. We aim to translate the NBSS into Chinese and use the CI approach to explore the thought processes of patients with NB in responding the Chinese Version of the NBSS, identify and modify the factors hinder the thought processes to enhance the face validity of the NBSS. Methods: The translation of the NBSS into Chinese was conducted with the guidance of the recommended frameworks. Patients with NB were recruited by purpose sampling. CI with the combination of thinking aloud and verbal probing techniques were used to explore thought processes. The interviews were transcribed and analyzed based on Tourangeau four-stage response model. Results: Two rounds of CI were carried out. The problems of comprehension, judgement and response mapping were identified in 8 items. Four items were revised based on the results of the interview. The revised items were verified and eventually integrated into the final version. Conclusion: The Chinese Version of the NBSS was easy to comprehend and use. The use of CI methodologies can increase the comprehensibility and cultural applicability of the NBSS, providing the evidence for the development of a clearer and more appropriate questionnaire.

Analysis of Variable Frequency Stimulation Sacral Neuromodulation for Different Genders: A Chinese Multicentric Prospective Clinical Study.

AIM: Sacral neuromodulation (SNM) is widely recognized as the essential treatment modality for patients suffering from various lower urinary tract disorders, particularly overactive bladder (OAB). This prospective study recruited patients who underwent variable frequency SNM treatment at six Chinese medical centers, aiming to evaluate the gender-specific effects of this intervention and provide precise guidance on its application for clinical management. METHODS: This prospective study was managed by Beijing Hospital, and six Chinese medical centers participated in this prospective research. Inclusion and exclusion criteria were established to screen patients based on the indication for SNM. During the research, all patients were required to record 72-h voiding diaries, urgency scores, and visual analogue scale (VAS) scores to reflect their disease symptoms. Additionally, subjective questionnaire surveys such as OAB symptom score (OABSS) and quality-of-life (Qol) score were recorded to reflect the patients' quality of life and treatment satisfaction. RESULTS: In this study, 52 patients (male patients: 25; female patients: 27) with OAB symptoms agreed to undergo variable frequency stimulation SNM therapy and finally convert to Stage II. Regarding the baseline outcomes, no significant differences were observed between the male and female groups. In terms of postoperative indicators, male patients showed a greater improvement in Qol scores compared to their female counterparts (20.06 ± 13.12 vs. 40.83 ± 26.06, p = 0.005). The results from VAS scores indicated that pain remission was more pronounced in male patients than in female patients (0.31 ± 0.87 vs. 1.67 ± 2.16, p = 0.02). Importantly, there was a statistically significant disparity in urinary urgency between males and females (male patients: 1.19 ± 1.56; female patients: 2.17 ± 1.52, p = 0.04). CONCLUSIONS: In our study, we found that variable frequency SNM treatment yielded sex-specific differences in therapeutic effects, with male patients having a better outcome in some metrics. This suggests that a patient's sex may influence when variable frequency SNM is used, and in the patient's follow-up. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ChiCTR2000036677.

Monoacylglycerol lipase blockades the senescence-associated secretory phenotype by interfering with NF-κB activation and promotes docetaxel efficacy in prostate cancer.

Metabolic reprogramming and cellular senescence greatly contribute to cancer relapse and recurrence. In aging and treated prostate, persistent accumulating senescence-associated secretory phenotype (SASP) of cancer cells often limits the overall survival of patients. Novel strategic therapy with monoacylglycerol lipase (MGLL) upregulation that counters the cellular and docetaxel induced SASP might overcome this clinical challenge in prostate cancer (PCa). With primary comparative expression and survival analysis screening of fatty acid (FA) metabolism signature genes in the TCGA PCa dataset and our single center cohort, MGLL was detected to be downregulated in malignancy prostate tissues and its low expression predicted worse progression-free and overall survival. Functionally, overexpression of MGLL mainly suppresses NF-κB-driven SASP (N-SASP) which mostly restricts the cancer cell paracrine and autocrine tumorigenic manners and the corresponding cellular senescence. Further investigating metabolites, we determined that MGLL constitutive expression prevents lipid accumulation, decreases metabolites preferably, and consequently downregulates ATP levels. Overexpressed MGLL inhibited IκBα phosphorylation, NF-κB p65 phosphorylation, and NF-κB nuclear translocation to deactivate NF-κB transcriptional activities, and be responsible for the repressed N-SASP, partially through reducing ATP levels. Preclinically, combinational treatment with MGLL overexpression and docetaxel chemotherapy dramatically delays tumor progression in mouse models. Taken together, our findings identify MGLL as a switch for lipase-related N-SASP suppression and provide a potential drug candidate for promoting docetaxel efficacy in PCa.

Cardiovascular disease burden in patients with urological cancers: The new discipline of uro-cardio-oncology.

Cancer remains a major cause of mortality worldwide, and urological cancers are the most common cancers among men. Several therapeutic agents have been used to treat urological cancer, leading to improved survival for patients. However, this has been accompanied by an increase in the frequency of survivors with cardiovascular complications caused by anticancer medications. Here, we propose the novel discipline of uro-cardio-oncology, an evolving subspecialty focused on the complex interactions between cardiovascular disease and urological cancer. In this comprehensive review, we discuss the various cardiovascular toxicities induced by different classes of antineoplastic agents used to treat urological cancers, including androgen deprivation therapy, vascular endothelial growth factor receptor tyrosine kinase inhibitors, immune checkpoint inhibitors, and chemotherapeutics. In addition, we discuss possible mechanisms underlying the cardiovascular toxicity associated with anticancer therapy and outline strategies for the surveillance, diagnosis, and effective management of cardiovascular complications. Finally, we provide an analysis of future perspectives in this emerging specialty, identifying areas in need of further research.

Causal relationship between anti-inflammatory drugs and cancer: a pan-cancer study with Mendelian randomization.

Background: Numerous epidemiological studies have elucidated the intricate connection between inflammation and cancer, highlighting how sustained inflammatory responses can fuel carcinogenesis by fostering proliferation, angiogenesis, and metastasis, while dampening immune responses and sensitivity to chemotherapy. Previous clinical investigations have underscored the potential of anti-inflammatory medications in either preventing or mitigating tumor formation. Here, the causal relationship between anti-inflammatory drugs and cancer was further explored through Mendelian randomization studies. Methods: Employing Mendelian randomization, we scrutinized the causal links between three anti-inflammatory drugs-NSAIDs, Aspirin, and Anilide-and 37 types of cancer. We primarily utilized inverse variance weighting (IVW) as the primary analytical approach to delineate the causal association between these drugs and cancer types. Concurrently, sensitivity analyses were conducted to ascertain the absence of horizontal pleiotropy and heterogeneity. Results: Our investigation revealed a discernible causal relationship between certain anti-inflammatory drugs and a subset of cancers, albeit without a pervasive impact across all cancer types. Specifically, NSAIDs exhibited a risk-reducing effect on non-small cell lung cancer (OR: 0.76, 95% CI: 0.59-0.97, p-value: 0.03) and gastric cancer (OR: 0.57, 95% CI: 0.34-0.98, p-value: 0.04). Conversely, aspirin was associated with an increased risk of oral malignant tumors (OR: 2.18, 95% CI: 1.13-4.21, p-value: 0.02). Notably, no statistically significant findings were observed for anilide drugs (p < 0.05). Conclusion: We identified several cancers with potential causal links to NSAIDs, including non-small cell lung cancer and gastric cancer. Despite our extensive analysis, we did not identify a substantial causal relationship between the use of anti-inflammatory drugs and the development of various cancers.

Development and validation of a nomogram to predict recurrence for clinical T1/2 clear cell renal cell carcinoma patients after nephrectomy.

OBJECTIVE: To develop and validate a nomogram for predicting recurrence-free survival (RFS) for clinical T1/2 (cT1/2) clear cell renal cell carcinoma (ccRCC) patients after nephrectomy. METHODS: Clinicopathological and survival data from 1289 cT1/2 ccRCC patients treated at the Second Hospital of Tianjin Medical University between 2017 and 2020 were included. Cox regression analysis was used to identify independent risk factors in 902 and 387 ccRCC patients in the training and validation cohorts, respectively, and construct the nomogram. The performance of the nomogram was assessed through calibration plots, time-dependent receiver operating characteristic (ROC) curves, C-index (concordance-index), and decision curve analysis (DCA). Kaplan-Meier curves were used to evaluate the probability of RFS in patients with different recurrence risks. RESULTS: Age, tumor size, surgical approach, Fuhrman grade, and pT3a upstage were identified as independent predictors of RFS. The area under the curve (AUC) for the 3-year and 5-year RFS ROC curves were 0.791 and 0.835 in the training cohort, and 0.860 and 0.880 in the validation cohort. The DCA and calibration plots demonstrated the optimal application and excellent accuracy of the nomogram for predicting 3-year and 5-year RFS. Kaplan-Meier curves revealed significant differences in RFS among the three risk groups in both the training and validation cohorts. Clinically, the developed nomogram provides a more precise tool for risk stratification, enabling tailored postoperative management and surveillance strategies, ultimately aiming to improve patient outcomes. CONCLUSIONS: We developed a nomogram for predicting RFS in cT1/2 ccRCC patients after nephrectomy with high accuracy. The clinical implementation of this nomogram can significantly enhance clinical decision-making, leading to improved patient outcomes and optimized resource utilization in the management of ccRCC.

Real-world clinical effectiveness of nonsurgical treatments for female with POP-Q stage II cystocele: a retrospective analysis of therapeutic efficacy.

Background: Patients with cystocele of pelvic organ prolapse quantification (POP-Q) stage II and below can be treated conservatively, but there are few reports on non-surgical treatment for these patients. This study aimed to present the real-world clinical effectiveness of nonsurgical treatment, including pelvic floor muscle training (PFMT), PFMT combined with pessary (PFMT + P), or non-ablative radiofrequency (PFMT + RF) for female with POP-Q stage II cystocele. Methods: We retrospectively analyzed females with POP-Q stage II cystocele between January 2020 and January 2022 who received PFMT, PFMT + P, or PFMT + RF treatment and were followed up for 12 months. Clinical parameters including Pelvic Floor Distress Inventory-20 questionnaire (PFDI-20), Persian version urinary incontinence quality of life questionnaire (I-QOL), POP-Q, pelvic floor Glazer evaluation, and trans-labial ultrasound at different time points were analyzed. Results: There were 147 participants enrolled. PFDI-20 and I-QOL scores were improved in all groups, but the mean decrement in the PFDI-20 scores (-14.28±8.57 and -9.78±8.25) was higher in the PFMT + P group than in the PFMT group and PFMT + RF group at both 6 and 12 months (P<0.05), and the mean I-QOL score (3.82±23.43 and 3.47±22.06) was higher in the PFMT + RP group at both 6 months and 12 months (P<0.05). The PFMT + P group also showed higher improvement rate (43.3%, P=0.03) in terms of changing the severity of cystocele (point Ba) and delta bladder neck-symphyseal distance (ΔBSD) (P<0.05) than the other 2 groups at 12 months. No statistical difference was found in the type-I and type-II myofiber function-based Glazer assessment among 3 groups. Conclusions: The combination of 2 treatment strategies seems to be superior to PFMT only for stage-II cystocele. Specific prolapse-related symptoms and objective indicators did improve more in the PFMT + P group, whereas stress urinary incontinence (SUI) symptoms and quality of life were improved in the PFMT + RP group.

Clinicopathological characteristics and typing of multilocular cystic renal neoplasm of low malignant potential.

BACKGROUND: Up until now, no research has been reported on the association between the clinical growth rate of multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) and computed tomography (CT) imaging characteristics. Our study sought to examine the correlation between them, with the objective of distinguishing unique features of MCRNLMP from renal cysts and exploring effective management strategies. AIM: To investigate optimal management strategies of MCRNLMP. METHODS: We retrospectively collected and analyzed data from 1520 patients, comprising 1444 with renal cysts and 76 with MCRNLMP, who underwent renal cyst decompression, radical nephrectomy, or nephron-sparing surgery for renal cystic disease between January 2013 and December 2021 at our institution. Detection of MCRNLMP utilized the Bosniak classification for imaging and the 2016 World Health Organization criteria for clinical pathology. RESULTS: Our meticulous exploration has revealed compelling findings on the occurrence of MCRNLMP. Precisely, it comprises 1.48% of all cases involving simple renal cysts, 5.26% of those with complex renal cysts, and a noteworthy 12.11% of renal tumors coexisting with renal cysts, indicating a statistically significant difference (P = 0.001). Moreover, MCRNLMP constituted a significant 22.37% of the patient population whose cysts demonstrated a rapid growth rate of ≥ 2.0 cm/year, whereas it only represented 0.66% among those with a growth rate below 2.0 cm/year. Of the 76 MCRNLMP cases studied, none of the nine patients who underwent subsequent nephron-sparing surgery or radical nephrectomy following renal cyst decompression experienced recurrence or metastasis. In the remaining 67 patients, who were actively monitored over a 3-year postoperative period, only one showed suspicious recurrence on CT scans. CONCLUSION: MCRNLMP can be tentatively identified and categorized into three types based on CT scanning and growth rate indicators. In treating MCRNLMP, partial nephrectomy is preferred, while radical nephrectomy should be minimized. After surgery, active monitoring is advisable to prevent unnecessary nephrectomy.

Phase 2 Study of Preoperative Tislelizumab in Combination with Low-dose Nab-Paclitaxel in Patients with Muscle-invasive Bladder Cancer.

BACKGROUND AND OBJECTIVE: Combinations of immune checkpoint inhibitors and nab-paclitaxel have achieved significant therapeutic effects in the treatment of advanced urothelial carcinoma. Our aim was to assess the efficacy and safety of tislelizumab combined with low-dose nab-paclitaxel in patients with muscle-invasive bladder cancer (MIBC). METHODS: TRUCE-01 was a single-arm phase 2 study that included 62 patients with T2-4a N0/X M0 MIBC tumors with predominant urothelial carcinoma histology. Eligible patients received three 21-d cycles of intravenous 200 mg tislelizumab on day 1 plus intravenous 200 mg nab-paclitaxel on day 2, followed by surgical assessment. The primary study endpoint was a clinical complete response (cCR). Treatment-related adverse event (TRAE) profiles were recorded according to Common Terminology Criteria for Adverse Events version 5.0. KEY FINDINGS AND LIMITATIONS: The safety analysis included all 62 patients and the efficacy analysis included 48 patients. The primary efficacy endpoint (cCR) was met by 25 patients (52%) patients. Among the 62 patients in the safety analysis, six (9.7%) had grade ≥3 TRAEs. CONCLUSIONS: Tislelizumab combined with low-dose nab-paclitaxel showed promising antitumor effectiveness and was generally well tolerated, which makes it an excellent preoperative therapy option for MIBC. PATIENT SUMMARY: We found that a combination of the drugs tislelizumab and low-dose nab-paclitaxel had satisfactory efficacy and safety for preoperative treatment of muscle-invasive bladder cancer.

Rationale for immune checkpoint inhibitors plus targeted therapy for advanced renal cell carcinoma.

Renal cell carcinoma (RCC) is a frequent urological malignancy characterized by a high rate of metastasis and lethality. The treatment strategy for advanced RCC has moved through multiple iterations over the past three decades. Initially, cytokine treatment was the only systemic treatment option for patients with RCC. With the development of medicine, antiangiogenic agents targeting vascular endothelial growth factor and mammalian target of rapamycin and immunotherapy, immune checkpoint inhibitors (ICIs) have emerged and received several achievements in the therapeutics of advanced RCC. However, ICIs have still not brought completely satisfactory results due to drug resistance and undesirable side effects. For the past years, the interests form researchers have been attracted by the combination of ICIs and targeted therapy for advanced RCC and the angiogenesis and immunogenic tumor microenvironmental variations in RCC. Therefore, we emphasize the potential principle and the clinical progress of ICIs combined with targeted treatment of advanced RCC, and summarize the future direction.

Expanding the Potential of Neoantigen Vaccines: Harnessing Bacille Calmette-Guérin Cell-Wall-Based Nanoscale Adjuvants for Enhanced Cancer Immunotherapy.

Personalized antitumor immunotherapy utilizing neoantigen vaccines holds great promise. However, the limited immunogenicity of existing recognized neoantigens and the inadequate stimulation of antitumor immune responses by conventional adjuvants pose significant challenges. To address these limitations, we developed a nanovaccine that combines a BCG bacterial cell wall skeleton (BCG-CWS) based nanoscale adjuvant (BCNA) with peptide neoantigens (M27 and M30). This integrated approach provides an efficient translational strategy for cancer immunotherapy. The BCNA nanovaccine, formulated with PLGA as an emulsifier, exhibits excellent biocompatibility and superior antigen presentation compared with conventional BCG-CWS adjuvants. Subcutaneous immunization with the BCNA-based nanovaccine effectively targets lymph nodes, eliciting robust innate and tumor-specific immune responses. Importantly, our findings demonstrate that BCNAs significantly enhance neoantigen immunogenicity while minimizing acute systemic toxicity. Furthermore, when combined with a mouse PD-L1 antibody, our strategy achieves complete tumor elimination in 60% of cases and prevents 25% of tumor growth in a melanoma mouse model. In conclusion, our BCNA-based nanovaccine represents a promising avenue for advancing personalized therapeutic neoantigen vaccines and holds significant implications for enhancing personalized immunotherapy and improving patient outcomes in the field of cancer treatment.

Multi-step strategies for synergistic treatment of urinary tract infections based on D-xylose-decorated antimicrobial peptide carbon dots.

Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC), often reoccur due to the formation of intracellular bacterial colonies (IBCs) and antibiotic resistance. Given the significance of YadC for UPEC infection in our previous study, we developed D-xylose-decorated ɛ-poly-L-lysine (εPL)-based carbon dots (D-xyl@εPLCDs) that can be traced, and employed multi-step approaches to elucidate the functional roles of D-xyl@εPLCDs in UPEC infection. Compared to undecorated particles, D-xyl@εPLCDs demonstrate YadC-dependent bacterial targeting and exhibit enhanced bactericidal activities both intracellularly and extracellularly. Moreover, pre-treatment of D-xyl@εPLCDs before infection blocked the subsequent adhesion and invasion of UPEC to bladder epithelial cells 5637. Increase of ROS production and innate immune responses were observed in bladder epithelial cells 5637 treated with D-xyl@εPLCDs. In addition, treatment of D-xyl@εPLCDs post-infection facilitated clearance of UPEC in the bladders of the UTI mouse model, and reduced ultimate number of neutrophils, macrophages and inflammatory responses raised by invaded bacteria. Collectively, we presented a comprehensive evaluating system to show that D-xyl@εPLCDs exhibits superior bactericidal effects against UPEC, making them a promising candidate for drug development in clinical UTI therapeutics.

Drug-Loaded Bacillus Calmette-Guérin Bacteria for Immuno-Chemo Combo Therapy in Bladder Cancer.

Intravesical Bacillus Calmette-Guérin (BCG) is a well-established strategy for managing high-risk nonmuscle-invasive bladder cancer (NMIBC); however, over half of patients still experience disease recurrence or progression. Although the combined intravesical instillation of various chemotherapeutic drugs is implemented in clinical trials to enhance the BCG therapy, the outcome is far from satisfying due to severe irritative effects and treatment intolerance at high doses. Therefore, it is adopted the "biotin-streptavidin strategy" to doxorubicin (DOX)-encapsulated nanoparticles within live BCG bacteria (DOX@BCG) to improve treatment outcomes. Adherence of BCG to the bladder epithelium helps precisely target DOX@BCG to the local tumor cells and simultaneously increases intratumoral transport of therapeutic drugs. DOX@BCG effectively inhibits cancer progression and prolongs the survival of rats/mice with orthotopic bladder cancer owing to synergism between BCG-immunotherapy, DOX-chemotherapy, and DOX-induced immunogenic tumor cell death; furthermore, it exhibits improved tolerance and biosafety, and establishes antitumor immunity in the tumor microenvironment. Therefore, the drug-loaded live BCG bacterial delivery system holds considerable potential for clinical translation in the intravesical treatment of bladder cancer.

Treatment patterns and healthcare resource utilization in patients with metastatic hormone-sensitive prostate cancer and nonmetastatic castration-resistant prostate cancer in China: a real-world observational study.

AIM: This study assessed the treatment patterns, healthcare resource utilization (HRU), costs, and annual prevalence and incidence of metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC) in China. METHODS: A retrospective study was conducted using electronic medical records (EMR) of patients with prostate cancer from three tertiary-care hospitals in China between January 2014 and March 2021. Descriptive statistics were used to analyze study outcomes. RESULTS: In total, 1086 patients with mHSPC and 679 patients with nmCRPC were included. From 2015 to 2020, the annual percentage of prevalent and incident cases of mHSPC decreased from 22.4% to 20.0% and 11.1% to 6.9%, respectively; for nmCRPC, these increased from 3.8% to 13.6% and 3.3% to 8.4%. Androgen-deprivation therapy and first-generation antiandrogens (bicalutamide or flutamide) were the most frequently prescribed prostate cancer-related medications at baseline and follow-up in patients with mHSPC. Bicalutamide was the most frequently prescribed prostate cancer-related medication during follow-up in patients with nmCRPC. For mHSPC, inpatient admission costs were the highest, with the median (interquartile range) costs per person-month being USD 403.00 (USD 85.50-1226.20), whereas outpatient visit costs were the highest for nmCRPC (USD 372.60 [USD 139.50-818.50]). LIMITATIONS: EMR-based study design did not capture treatment patterns, HRU and associated costs, and healthcare encounters that occurred outside of participating hospitals, which could have led to underestimation of the true disease burden. CONCLUSIONS: A contrasting trend of a decline in the prevalence and incidence of mHSPC and an increase in these for nmCRPC was observed between 2015 and 2020 in China. Androgen-deprivation therapy and first-generation antiandrogens were the most frequently prescribed prostate cancer-related medications. Healthcare resource utilization was driven by inpatient costs in mHSPC and outpatient costs in nmCRPC.

Tumor margin irregularity degree is an important preoperative predictor of adverse pathology for clinical T1/2 renal cell carcinoma and the construction of predictive model.

PURPOSE: To explore the critical role of the tumor margin irregularity degree (TMID) of renal tumors in predicting adverse pathology of patients with clinical T1/2 (cT1/2) renal cell carcinoma (RCC). METHODS: A total of 821 patients with cT1/2 RCC undergoing nephrectomy in the Second Hospital of Tianjin Medical University between January 2017 and December 2020 were reviewed. The tumor margin irregularity (TMI) was classified into renal mass with locally raised protrusion and smooth margin called 'lobular', sharply and unsmooth nodular margin called 'spiculation', blurred margins between tumor and renal parenchyma or a completely irregular and non-elliptical shape. The ratio between the number of irregular cross-sections (X) and the number of total cross-sections from top to bottom occupied (Y) was defined as TMID (X/Y). The logistic regression was performed to determine the independent predictors of adverse pathology, and the Kaplan-Meier curve and log-rank test were used to analyze the survival outcomes. RESULTS: Among 821 cT1/2 RCC patients, 245 (29.8%) had adverse pathology. The results of the univariate and multivariate logistic regressions showed that the age, tumor size, hemoglobin, and TMID were the independent predictors of adverse pathology. Incorporation of TMID could increase the discrimination of the predictive model with the area under curve (AUC) of ROC curves increasing from 0.725 to 0.808. Patients with adverse pathology or higher TMID both had significantly shorter recurrence-free survival (RFS). CONCLUSION: The nomogram model incorporated with TMID for predicting adverse pathology could increase its discrimination, calibration, and clinical application values, compared with the models without TMID.

CT features based preoperative predictors of aggressive pathology for clinical T1 solid renal cell carcinoma and the development of nomogram model.

BACKGROUND: We aimed to identify preoperative predictors of aggressive pathology for cT1 solid renal cell carcinoma (RCC) by combining clinical features with qualitative and quantitative CT parameters, and developed a nomogram model. METHODS: We conducted a retrospective study of 776 cT1 solid RCC patients treated with partial nephrectomy (PN) or radical nephrectomy (RN) between 2018 and 2022. All patients underwent four-phase contrast-enhanced CT scans and the CT parameters were obtained by two experienced radiologists using region of interest (ROI). Aggressive pathology was defined as patients with nuclear grade III-IV; upstage to pT3a; type II papillary renal cell carcinoma (pRCC), collecting duct or renal medullary carcinoma, unclassified RCC or sarcomatoid/rhabdoid features. Univariate and multivariate logistic analyses were used to determine significant predictors and develop the nomogram model. To evaluate the accuracy and clinical utility of the nomogram model, we used the receiver operating characteristic (ROC) curve, calibration plot, decision curve analysis (DCA), risk stratification, and subgroup analysis. RESULTS: Of the 776 cT1 solid RCC patients, 250 (32.2%) had aggressive pathological features. The interclass correlation coefficient (ICC) of CT parameters accessed by two reviewers ranged from 0.758 to 0.982. Logistic regression analyses showed that neutrophil-to-lymphocyte ratio (NLR), distance to the collecting system, CT necrosis, tumor margin irregularity, peritumoral neovascularity, and RER-NP were independent predictive factors associated with aggressive pathology. We built the nomogram model using these significant variables, which had an area under the curve (AUC) of 0.854 in the ROC curve. CONCLUSIONS: Our research demonstrated that preoperative four-phase contrast-enhanced CT was critical for predicting aggressive pathology in cT1 solid RCC, and the constructed nomogram was useful in guiding patient treatment and postoperative follow-up.

TNIK drives castration-resistant prostate cancer via phosphorylating EGFR.

The development of castration-resistant prostate cancer (CRPC) is driven by intricate genetic and epigenetic mechanisms. Traf2- and Nck-interacting kinase (TNIK) has been reported as a serine/threonine kinase associated with tumor cell proliferation or unfavorable cancer behavior. The microarray approach revealed a substantial upregulation of TNIK expression levels, enabling us to investigate the functional behaviors of the TNIK gene in CRPC. Specifically, we discovered that AR suppresses TNIK gene transcription in LNCaP and C4-2 cells by forming a complex with H3K27me3. Following the reduction of AR levels induced by androgen deprivation therapy (ADT), TNIK is recruited to activate EGFR signaling through phosphorylation in C4-2 cells, thereby promoting CRPC progression. Our findings unveil a regulatory role of AR as a repressor for TNIK while also highlighting how TNIK activates the EGFR pathway via phosphorylation to drive CRPC progression. Consequently, targeting TNIK may represent an appealing therapeutic strategy for CRPC.

Comparison of Regional Saturation Biopsy, Targeted Biopsy, and Systematic Biopsy in Patients with Prostate-specific Antigen Levels of 4-20 ng/ml: A Prospective, Single-center, Randomized Controlled Trial.

BACKGROUND: Despite the use of multiparametric magnetic resonance imaging (mpMRI)-guided targeted biopsy (TB) to identify suspicious prostate lesions, it may still miss clinically significant prostate cancer (csPCa) or result in false-negative findings. Recent evidence suggests that combining biopsies taken from within and around magnetic resonance imaging (MRI) lesions can improve the detection of csPCa. OBJECTIVE: This study aimed to compare the diagnostic performance of the regional saturation biopsy (RSB) method, involving template-based nine-core biopsies for suspected regions, with that of the MRI-directed TB and/or the systematic biopsy (SB) methods in biopsy-naïve patients with prostate-specific antigen (PSA) levels ranging from 4 to 20 ng/ml. DESIGN, SETTING, AND PARTICIPANTS: A prospective, single-center, randomized controlled trial included 434 biopsy-naïve patients with suspected lesions on mpMRI and PSA levels between 4 and 20 ng/ml (from January 2022 to July 2023). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The detection rates of csPCa for the RSB, TB, and SB methods were analyzed using the McNemar test for intrapatient comparisons. The Fisher's exact test was used for comparisons between RSB and TB. RESULTS AND LIMITATIONS: The RSB approach yielded a significantly higher detection rate of csPCa than both the TB approach (44.1% vs 31.8%, p = 0.01) and the SB approach (44.1% vs 34.1%, p = 0.03). The RSB approach exhibited a comparable detection rate of csPCa (44.1% vs. 40.7%, p = 0.3) to the combined approach (TB + SB), while requiring fewer biopsy cores and a higher positive core number to avoid sampling the entire prostate gland (32.7% vs 18.3%, p < 0.001). Upon conducting a whole-mount histopathological analysis, it was observed that the RSB approach successfully identified 97% (32 out of 33) of the prostate cancer foci as the index lesion, whereas only 59.18% (29 out of 49) were classified as index lesions using the SB approach. Furthermore, mpMRI underestimated the average diameter of histological tumor size by a median of 0.76 cm, highlighting the importance of an optimal biopsy area for the RSB procedure. CONCLUSIONS: For patients with suspected lesions on mpMRI and PSA levels between 4 and 20 ng/ml, the RSB approach has shown improved detection of clinically significant prostate cancer, accurately identifying index lesions, and minimizing biopsy cores compared with the MRI-directed TB and SB approaches. PATIENT SUMMARY: For patients with suspected lesions on multiparametric magnetic resonance imaging and prostate-specific antigen levels between 4 and 20 ng/ml, the regional saturation biopsy method provides enhanced detection of clinically significant prostate cancer, as well as precise identification of index lesions, surpassing both magnetic resonance imaging-directed targeted biopsy and the systematic biopsy method.

Investigating High-risk Factors, Precise Diagnosis, and Treatment of Castration-Resistant Prostate Cancer (CRPC).

BACKGROUND: The treatment of metastatic castration-resistant prostate cancer (mCRPC) in the actual world currently presents difficulties. In light of this, it is crucial to investigate high-risk factors for the progression of advanced prostate cancer and to identify methods for delaying the onset of CRPC. AIMS: This study aimed to explore the high-risk factors that impact the progression of prostate cancer and emphasize the significance of precise diagnosis and treatment based on etiological classification in the clinical management of castration-resistant prostate cancer. METHODS: A retrospective analysis was conducted on 277 newly diagnosed cases of PCa treated with endocrine therapy. A follow-up was done on prostate-specific antigen (PSA) levels and testosterone. Additionally, a prospective analysis was performed on the clinical data of 60 patients with CRPC. Following the principle of '4W1H', 30 patients were included in the precision treatment group for a second biopsy and related tests, while another 30 patients were included in the conventional treatment group. The therapeutic effect and prognosis of the two groups were observed. RESULTS: Distant metastasis (HR = 1.879, 95% CI: 1.311 ~ 2.694, P = 0.001), PSA nadir > 0.2 ng/mL (HR = 1.843, 95% CI: 1.338 ~ 2.540, P = 0.001), testosterone nadir > 20 ng/dL (HR = 1.403, 95% CI: 1.035 ~ 1.904, P = 0.029), and time to testosterone nadir > 6 months (HR = 1.919, 95% CI: 1.364 ~ 2.701, P = 0.001) were risk factors for the progression to CRPC. Patients in the CRPC group were treated with precision therapy and conventional therapy based on their molecular subtyping. The precision treatment group showed a significantly prolonged median PSA progression-free survival compared to the conventional treatment group (16.0 months vs. 13.0 months, P=0.025). The median radiographic progression-free survival was also significantly extended in the precision treatment group compared to the conventional treatment group (21.0 months vs. 16.0 months, P=0.042). CONCLUSION: Patients with prostate cancer diagnosed with distant metastasis at initial presentation require early intervention. Close monitoring of PSA and serum testosterone changes is necessary during the process of endocrine therapy. After entering the CRPC stage, the etiological classification precision treatment can improve the therapeutic effect and improve the prognosis of patients.