Utilization trend of prebiopsy multiparametric magnetic resonance imaging and its impact on prostate cancer detection: Real-world insights from a high-volume center in southwest China.

BACKGROUND: Data on the utilization and effects of prebiopsy prostate multiparametric magnetic resonance imaging (mpMRI) to support its routine use in real-world setting are still scarce. OBJECTIVE: To evaluate the change of clinical practice of prebiopsy mpMRI over time, and assess its diagnostic accuracy. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed data from 6168 patients who underwent primary prostate biopsy (PBx) between January 2011 and December 2021 and had prostate-specific antigen (PSA) values ranging from 3 to 100 ng/mL. INTERVENTION: Prebiopsy MRI at the time of PBx. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed general linear regression and to elucidate trends in the annual use of prebiopsy mpMRI and conducted multivariable logistic regression to evaluate the potential benefits of incorporating prebiopsy mpMRI for prostate cancer (PCa) detection. RESULTS AND LIMITATIONS: The utilization of prebiopsy mpMRI significantly increased from 9.2% in 2011 to 75.0% in 2021 (p < 0.001). In addition, prebiopsy mpMRI significantly reduced negative PBx by 8.6% while improving the detection of clinically significant PCa (csPCa) by 7.0%. Regression analysis showed that the utilization of prebiopsy mpMRI was significantly associated with a 48% (95% confidence interval [CI]: 1.19-1.84) and 36% (95% CI: 1.12-1.66) increased PCa detection rate in the PSA 3-10 ng/mL and 10-20 ng/mL groups, respectively; and a 34% increased csPCa detection rate in the PSA 10-20 ng/mL group (95% CI: 1.09-1.64). The retrospective design and the single center cohort constituted the limitations of this study. CONCLUSIONS: Our study demonstrated a notable rise in the utilization of prebiopsy mpMRI in the past decade. The adoption of this imaging technique was significantly associated with an increased probability of detecting prostate cancer. PATIENT SUMMARY: From 2011 to 2021, we demonstrated a steady increase in the utilization of prebiopsy mpMRI among biopsy-naïve men. We also confirmed the positive impact of prebiopsy mpMRI utilization on the detection of prostate cancer.

The Prognostic Value of Preoperative Naples Prognostic Score in Upper Tract Urothelial Carcinoma Patients after Radical Nephroureterectomy.

This study aims to determine the prognostic value of preoperative Naples prognostic score (NPS) on survival outcomes in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). We conducted a retrospective study about UTUC patients at West China Hospital from January 2015 to June 2019. The X-Tile program was used to identify the optimal cutoff value of NPS. Overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) were the endpoints of interest. Kaplan-Meier curves were used to estimate survival and Cox proportional hazard model was used for risk assessment. A total of 237 UTUC patients after RNU were identified and the threshold of NPS was determined to be 2. Preoperative high-NPS was associated with inferior OS (p = 0.004), CSS (p = 0.002) and PFS (p = 0.008), especially in locally advanced UTUC patients. Preoperative NPS was an independent predictor for OS (HR: 1.78; 95% CI: 1.08, 2.93), CSS (HR: 1.87; 95% CI: 1.11, 3.14) and PFS (HR: 1.60; 95% CI: 1.02, 2.50). The addition of NPS into the predictive model consisting of predictors from multivariate Cox regression resulted in better prediction performance. Preoperative NPS was a novel and reliable predictor for survival in UTUC patients after RNU, and should be further explored.

Serum α-hydroxybutyrate dehydrogenase as a biomarker for predicting survival outcomes in patients with UTUC after radical nephroureterectomy.

PURPOSE: We aimed to determine the prognostic value of α-hydroxybutyrate dehydrogenase (α-HBDH) in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively enrolled the data of 544 UTUC patients at West China Hospital from May 2003 to June 2019. Cancer-specific survival (CSS) was the endpoint of interest. The optimal cutoff value of α-HBDH was identified by X-Tile program. After propensity score matching (PSM), we utilized Kaplan‒Meier curves to estimate survival and Cox proportional hazard model for risk assessment. A nomogram was built based on the results of multivariate analysis, and calibration curve, time-dependent receiver operating characteristic (ROC) curves and decision curve analysis were also performed to evaluate the predictive accuracy. RESULTS: Overall, 394 and 150 patients were divided into the α-HBDH-low group and α-HBDH -high group at the cutoff value of 158 U/L, respectively. After PSM, the two groups were well matched for all confounding factors. High α-HBDH was associated with inferior CSS (P = 0.006), and preoperative α-HBDH was an independent predictor for CSS (HR: 1.36; 95% CI:1.08, 1.80), especially in localized UTUC patients (HR: 2.04; 95% CI:1.11, 3.74). Furthermore, the nomogram based on α-HBDH achieved great predictive ability for CSS with areas under the curves of 0.800 and 0.778 for 3-year and 5-year CSS, respectively. CONCLUSION: Serum α-HBDH was a novel and reliable biomarker for predicting survival outcomes in UTUC patients after RNU but should be further explored.

Ureteral urothelial carcinoma with squamous cell carcinoma and sarcomatoid carcinoma differentiation: a case report.

BACKGROUND: Upper urinary tract urothelial carcinoma (UTUC) with multiple pathological types is extremely rare in the clinic, but the recurrence rate and mortality these patients are high. At present, there is no standard treatment for such cases. CASE PRESENTATION: We reported a case of ureteral urothelial carcinoma with squamous cell carcinoma and sarcomatoid carcinoma differentiation and rapid ileal metastasis and reviewed the literature related to different pathological types of upper urinary tract tumours to explore the diagnosis, treatment and prognosis characteristics of the disease, enhance our understanding of its clinical manifestations and history of evolution and provide guidance for avoiding missed diagnosis and misdiagnosis. CONCLUSION: There is no standard treatment for urinary malignant tumours with multiple pathological types; radical surgery is considered a suitable choice. Chemotherapy, targeted drug therapy and immunotherapy may be beneficial to the survival of patients. In short, these patients have a high risk of recurrence and metastasis and a poor prognosis.

Water for preventing urinary stones.

BACKGROUND: Urinary stone disease is a common condition characterised by increasing prevalence and high rates of recurrence. Observational studies have reported that increased water intake played a role in the prevention of urinary stone formation but with limited strength of evidence. OBJECTIVES: To compare the effects of increased water intake with standard water intake for the prevention of urinary stone formation in participants with or without a history of urinary stones. SEARCH METHODS: We performed a systematic search of PubMed (MEDLINE), EMBASE (Ovid) and the Cochrane Library to 15 October 2019. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. We did not apply any restrictions to publication language or publication status. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs looking at the benefits and harms of increased water intake versus standard water intake for the prevention of urinary stone formation in participants with or without a history of urinary stones. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently extracted data and assessed the risk of bias of included studies. We pooled dichotomous outcomes (e.g. incidence/recurrence rate of urinary stones; adverse events) using risk ratios (RRs) with 95% confidence intervals (CIs). We calculated hazard ratio (HRs) and corresponding 95% CIs to assess the intervention effect for time-to-event outcomes. We assessed the certainty of the evidence by using the GRADE criteria. MAIN RESULTS: Our search identified no RCTs investigating the role of increased water intake for the prevention of urinary stone formation in participants with no history of urinary stones (primary prevention). We found one RCT assessing the effects of increased water intake versus standard water intake for the prevention of urinary stone formation in people with a history of urinary stones (secondary prevention). This trial randomised 220 participants (110 participants in the intervention group with increased water intake and 110 in the control group with standard water intake). Increased water intake was defined as achieving a urine volume of at least 2.0 L per day by drinking water. Based on this study, increased water intake may decrease stone recurrences (RR 0.45, 95% CI 0.24 to 0.84; 199 participants; low-certainty evidence); this corresponds to 149 fewer (43 fewer to 205 fewer) stone recurrences per 1000 participants with 270 stone recurrence per 1000 participants over five years in the control group. Increased water intake may also prolong the time to urinary stone recurrence compared to standard water intake (HR 0.40, 95% CI 0.20 to 0.79; 199 participants; low-certainty evidence); based on a stone recurrence rate of 270 per 1000 participants over five years, this corresponds to 152 fewer (209 fewer to 50 fewer) recurrences per 1000 participants. For both outcomes we downgraded the certainty of evidence for study limitations and imprecision. We found no evidence for the outcome of adverse events AUTHORS' CONCLUSIONS: We found no RCT evidence on the role of increased water intake for primary prevention of urinary stones. For secondary prevention, increased water intake achieving a urine volume of at least 2.0 L/day may reduce urinary stone recurrence and prolong time to recurrence for people with a history of urinary stone disease. However, our confidence in these findings is limited. We did not find evidence for adverse events.

Diagnostic Role of Magnetic Resonance Imaging-Targeted Biopsy for Prostate Cancer in Biopsy-Naïve Men: A Meta-Analysis.

OBJECTIVE: To investigate the diagnostic role of magnetic resonance imaging (MRI)-targeted biopsy (TB) for prostate cancer (PCa) in biopsy-naïve men. MATERIALS AND METHODS: Own control studies and randomized controlled trials (RCTs) up to December 2018 were identified via a systematic search of PubMed, Embase, Ovid, and the Cochrane Library. We pooled relative sensitivity (or risk ratio [RR]) to compare diagnostic efficiency for PCa and clinically significant PCa (csPCa) between TB and systematic biopsy (SB). The independent role of either biopsy pathway was evaluated for participants with positive/negative MRI. RESULTS: Thirty-one studies consisting of 25 own control studies and 6 RCTs were included. We identified 4,020 biopsy-naïve men with positive MRI who underwent two biopsies concurrently, with PCa/csPCa detection rates of 65.90 and 45.13%, respectively. TB and SB did not differ in the detection of any PCa (RR 0.98, 95% confidence interval [CI] 0.92-1.05). However, TB detected more csPCa (RR 1.19, 95% CI 1.10-1.30) and more PCa with a Gleason score ≥3+4 (RR 1.20, 95% CI 1.07-1.34). Using a combined test as a reference, omitting SB resulted in detecting 12.81% less csPCa and 20.76% less clinically insignificant PCa (cinsPCa), and omitting TB resulted in detecting 25.69% less csPCa and 10.8% more cinsPCa. For patients with negative MRI, omitting SB led to underdetection of 30.29% of any PCa (10.9% of csPCa). CONCLUSIONS: Combining TB and SB increased the diagnostic accuracy of csPCa for biopsy-naïve men with positive MRI, and omitting SB for patients with a negative MRI would lead to the underdetection of nearly 10% of csPCa.

Tumor-associated macrophages promote bladder tumor growth through PI3K/AKT signal induced by collagen.

The tumor microenvironment is associated with various tumor progressions, including cancer metastasis, immunosuppression, and tumor sustained growth. Tumor-associated macrophages (TAMs) are considered an indispensable component of the tumor microenvironment, participating in the progression of tumor microenvironment remodeling and creating various compounds to regulate tumor activities. This study aims to observe enriched TAMs in tumor tissues during bladder cancer development, which markedly facilitated the proliferation of bladder cancer cells and promoted tumor growth in vivo. We determined that TAMs regulate tumor sustained growth by secreting type I collagen, which can activate the prosurvival integrin α2ß1/PI3K/AKT signaling pathway. Furthermore, traditional chemotherapeutic drugs combined with integrin α2ß1 inhibitor showed intensive anticancer effects, revealing an innovative approach in clinical bladder cancer treatment.

Comparative efficacy and safety of phosphodiesterase type 5 inhibitors for erectile dysfunction in diabetic men: a Bayesian network meta-analysis of randomized controlled trials.

PURPOSE: To compare the efficacy and safety profiles of different phosphodiesterase-5 inhibitors (PDE5Is) administrations for erectile dysfunction (ED) in diabetic men, including on-demand (PRN) and regular regimens (OAD). MATERIALS AND METHODS: Searches were carried out in four electronic databases: PubMed (until April 17th, 2017); Scopus (until April 17th, 2017); Embase (until April 17th, 2017); and Cochrane (until April 18th, 2017). The outcomes for this study are as follows: (1) Global Assessment Question (GAQ) positive response rate; (2) changes from baseline to the end of the study in Erectile Function Domain of International Index of Erectile Function (IIEF-EF); and (3) treatment-related adverse events (TRAEs). The comparative effects of PDE5I regimens were analyzed with random-effect models in a Bayesian Framework using the GeMTC R package. RESULTS: We identified 1056 records, of which 15 randomized trials with 5274 patients were included. The included studies covered eight kinds of PDE5I administration: avanafil PRN; mirodenafil PRN; sildenafil PRN; tadalafil PRN; tadalafil OAD; udenafil PRN; udenafil OAD; vardenafil PRN; and placebo. In surface under the cumulative ranking curve analysis, vardenafil PRN ranked first, third and first, and mirodenafil PRN ranked second, first and second in GAQ, IIEF-EF, and TRAEs, respectively. CONCLUSIONS: PDE5I administrations were generally efficient and well-tolerated in diabetic men. Among these administrations, vardenafil PRN and mirodenafil PRN seem to have a possible advantage of efficacy and avoiding adverse effects compared to others. There is no significant difference between regular and on-demand regimens of PDE5Is.

Large Cell Neuroendocrine Carcinoma of the Prostate: A Systematic Review and Pooled Analysis.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the prostate is an extremely rare entity, and the clinicopathological course, potential effective treatment, and prognosis are yet to be elucidated. MATERIALS AND METHODS: A systematic search in Pubmed, Embase, and Ovid from inception to January 2019 was conducted. We reviewed each individual case of prostatic LCNEC and summarized specific features and outcomes for this rare pathologic entity. RESULTS: Thirteen studies with a total of 20 patients (mean age: 70.3, range 43-87) were included in our review. Seventeen patients harbored primary LCNEC of the prostate, of which 9 patients were diagnosed with de novo carcinoma, and 8 patients were with a history of prostatic adenocarcinoma treated with hormonal therapy (mean duration: 2.9 years, range 2-5). The other 3 patients were diagnosed with metastatic LCNEC originating from lung (2 cases) and bladder (1 case). All patients met the diagnostic criteria of the typical morphological features as well as immunohistochemical staining results. Nearly all primary de novo LCNEC of the prostate were at a late stage at initial diagnosis. The pattern of distant metastasis resembled that of prostatic adenocarcinoma with the most common sites as bone spread (8/16, 50%). Most patients received systematic chemotherapy after diagnosis; however, the prognosis remained poor and patients deteriorated rapidly but with exception. Three reported cases in the context of de novo LCNEC admixed with prostatic adenocarcinoma kept sustained response to androgen deprivation therapy (ADT) and achieved obviously better survival outcomes compared with other patients. CONCLUSIONS: LCNEC of the prostate is a rare entity that mostly occurs after long-standing hormonal therapy of prostatic adenocarcinoma. The prognosis was universally poor irrespective of the systematic chemotherapy. However, patients of de novo tumor mixed with prostatic adenocarcinoma may respond to ADT and harbor a better outcome than those of pure de novo or post-ADT LCNEC of the prostate.

Reversal of docetaxel resistance in prostate cancer by Notch signaling inhibition.

Acquired docetaxel (Doc) resistance in hormone-refractory prostate cancer (HRPC) remains an ongoing clinical challenge, resulting in failed chemotherapy and tumor recurrence. However, the mechanism of Doc-resistance development in prostate cancer cells is still unclear. Here, we observed a subpopulation of prostate cancer cells, in both Doc-resistant cell lines and the tumors of patients with HRPC, which show stem cell markers and greater tumorigenic potential. Those stem-like prostate cancer cells show high expression of ABCB1, which encodes multidrug resistance-related protein P-glycoprotein, leading to the Doc-resistance in prostate cancer. Moreover, we found that Notch signaling pathway activation in Doc-resistant cell lines and tumor tissues of patients with HRPC correlated with tumorigenicity and the development of Doc resistance. Here, we revealed that a combination of Doc and a Notch signaling inhibitor overcomes Doc resistance and increases the survival of mice with Doc-resistant xenografts. Therefore, targeting the Notch signaling pathway may be a promising strategy to overcome the Doc-resistant cancer in the clinic.

Efficacy of PDE5Is and SSRIs in men with premature ejaculation: a new systematic review and five meta-analyses.

PURPOSE: To clarify the efficacy of phosphodiesterase-5 inhibitors (PDE5Is) and selective serotonin reuptake inhibitors (SSRIs) in men with premature ejaculation (PE). METHODS: We searched the PubMed, Embase, and Cochrane Library databases to identify all randomized, controlled trials (RCTs) and compared the results, including intravaginal ejaculation latency time, satisfaction, intercourse per-week and side effects after treatment with PDE5I or SSRIs versus placebo, combined use of PDE5I with SSRIs versus PDE5I or SSRIs alone, and PDE5I versus SSRIs for treating PE. RESULTS: The study inclusion criteria were met by 23 studies (ten RCTs with five crossover studies) involving 6145 patients. The data synthesized from these studies indicated that the efficacy of PDE5Is and SSRIs was better than that of placebo (p < 0.00001; p < 0.00001); however, more patients had side effects while taking PDE5Is and SSRIs (p < 0.00001; p < 0.00001). The efficacy of the combined treatment was significantly better than that of PDE5Is or SSRIs alone (p < 0.00001; p < 0.00001); however, more patients had side effects from the combined treatment than from SSRIs (p = 0.0002), with no significant difference in PDE5Is (p = 0.5). The efficacy of PDE5Is was better than that of SSRIs (p = 0.006), and no significant difference was observed in the frequency of side effects (p = 0.93). CONCLUSIONS: PDE5Is were significantly more effective than placebo or SSRIs for treating PE, while SSRIs were better than placebo. The combined treatment had better efficacy than PDE5Is or SSRIs alone.

[The Feasibility of CT Attenuation Value to Predict the Composition of Upper Urinary Calculi and Success Rate of Extracorporeal Shock Wave Lithotripsy].

OBJECTIVE: To explore the feasibility of CT attenuation value (CTvalue) to predict the composition of upper urinary calculi and the number of shock waves (NSW) and success rate (SR) of extracorporeal shock wave lithotripsy (ESWL). METHODS: A total of 146 patients with upper urinary calculi treated by ESWL were included. CT scan was performed before ESWL. Upper urinary calculi with the maximum diameters of less than or equal to 2 cm were included. Infrared spectroscopy was used to analyze the composition of calculi. The effect of ESWL was estimated at 1 month followup. The factors that influence NSW and SR of ESWL were analyzed by correlation analysis. RESULTS: The CTvalue of calcium calculi were larger than that of noncalcium calculi ( P<0.001). The differences of NSW,SR of ESWL and CTvalues of calculi between the patients with different ages,skintostone distances and genders were not statistically significant. The partial correlation analysis found that CTvalue and long diameter of calculi were positively correlated with the NSW ( P<0.05). This result was consistent in subgroup analysis (stone site: kidney or ureter). CTvalue and long diameter of calculi were negatively correlated with SR of ESWL ( P<0.05). However,the CTvalue of ureteral calculi was not correlated with SR of ESWL in subgroup analysis. CONCLUSION: The power of CTvalue to predict upper urinary calculi composition is insufficient. Higher CTvalue suggests more NSW in ESWL,but CTvalue is not suitable to predict SR of ESWL.

Mycobacterium tuberculosis PE25/PPE41 protein complex induces activation and maturation of dendritic cells and drives Th2-biased immune responses.

Mycobacterium tuberculosis evades innate host immune responses by parasitizing macrophages and causes significant morbidity and mortality around the world. A mycobacterial antigen that can activate dendritic cells (DCs) and elicit effective host innate immune responses will be vital to the development of an effective TB vaccine. The M. tuberculosis genes PE25/PPE41 encode proteins which have been associated with evasion of the host immune response. We constructed a PE25/PPE41 complex gene via splicing by overlapping extension and expressed it successfully in E. coli. We investigated whether this protein complex could interact with DCs to induce effective host immune responses. The PE25/PPE41 protein complex induced maturation of isolated mouse DCs in vitro, increasing expression of cell surface markers (CD80, CD86 and MHC-II), thereby promoting Th2 polarization via secretion of pro-inflammatory cytokines IL-4 and IL-10. In addition, PE25/PPE41 protein complex-activated DCs induced proliferation of mouse CD4(+) and CD8(+) T cells, and a strong humoral response in immunized mice. The sera of five TB patients were also highly reactive to this antigen. These findings suggest that interaction of the PE25/PPE41 protein complex with DCs may be of great immunological significance.

The use of internal stents in chronic ureteral obstruction.

PURPOSE: Despite the lack of a well delineated definition, chronic ureteral obstruction imposes significant quality of life loss, increased pathological morbidity and risk of mortality as well as substantial economic burden. Ureteral stenting serves as an important therapeutic option to alleviate obstruction. Thus, we assessed the recently published literature on chronic ureteral obstruction; treatment options; types, benefits and shortcomings of current ureteral stents; as well as outcomes and complications of chronic ureteral stenting, with the goal of providing concise management guidelines. MATERIALS AND METHODS: A systemic literature review was performed on Embase™, PubMed®, Cochrane Controlled Trials Register and Google Scholar™ on ureteral obstruction and internal ureteral stents. Relevant reviews, original research articles and their cited references were examined, and a synopsis of original data was generated on a clinically oriented basis. RESULTS: Chronic ureteral obstruction can be classified into compression that is either intrinsic or extrinsic to the ureteral wall, or obstruction that is of a benign or malignant origin. Patients with malignant ureteral obstruction generally have a poor prognosis and are often difficult to treat. The aim of stenting is to adequately drain the upper urinary tracts while minimizing hospitalization and the negative impact on quality of life. Facing the challenge of chronic ureteral obstruction, novel stents with new compositions, materials, coatings and designs have been developed. Metallic stents are emerging as efficacious and financially viable alternatives. Early stent related complications include iatrogenic injury, stent migration or patient discomfort, while late complications include infection, difficulties with stent exchange, hardware malfunction, infection and stent encrustation. CONCLUSIONS: Stenting in chronic ureteral obstruction is a complex and challenging problem. Much work is being done in this area and many options are being explored.

A systematic review and meta-analysis for human epidermal growth factor receptor 2 on upper tract urothelial carcinoma patients.

OBJECTIVE: The expression and significance of human epidermal growth factor receptor 2 (Her2) in upper tract urothelial carcinoma (UTUC) remains controversial. Thus, we aimed to systemically review the Her2 expression in UTUC patients and its relationship with pathological characters and clinical outcomes with meta-analysis. MATERIALS AND METHODS: A systematically computerized search in PubMed, Scopus, Embase and Cochrane was conducted. From a total of 454 related articles, 35 articles were finally reviewed and 16 papers were chosen for further analysis. Pathological characters included tumor stage, grade, lymph node metastasis (LNM) and lymphovascular invasion (LVI). The clinical outcomes included overall survival (OS), recurrence-free survival (RFS), cancer specific survival (CSS), metastatic-free survival (MFS) and progression-free survival (PFS). RevMan software was used for meta-analyses. RESULTS: In total 16 studies from 1994 to 2020 were chosen, 14 studies used immunohistochemistry to assess the expression of Her2 and 5 studies used in situ hybridization, with a positive rate of 0 to 74.0% and 7.2 to 18.1%, respectively. Her2-positive was significantly associated with stage (pooled HR 1.86; 95 % CI 1.43-2.42), grade (pooled HR 2.81; 95 % CI 1.01-7.85) and LNM (pooled HR 1.93; 95 % CI 1.18-3.15). However, there was no statistically relationship between Her2-positive with LVI (pooled HR 1.48; 95 % CI 0.64-3.46) and RFS (pooled HR 1.41; 95 % CI 0.98-1.83). CONCLUSIONS: This review indicated that UTUC patients with Her2-positive tended to develop higher stage and grade tumors and LNM. The Her2 expression in UTUC patients deserves further investigation in the future.

Wnt/ß-catenin signaling pathway in carcinogenesis and cancer therapy.

The Wnt/ß-catenin signaling pathway plays a crucial role in various physiological processes, encompassing development, tissue homeostasis, and cell proliferation. Under normal physiological conditions, the Wnt/ß-catenin signaling pathway is meticulously regulated. However, aberrant activation of this pathway and downstream target genes can occur due to mutations in key components of the Wnt/ß-catenin pathway, epigenetic modifications, and crosstalk with other signaling pathways. Consequently, these dysregulations contribute significantly to tumor initiation and progression. Therapies targeting the Wnt/ß-catenin signaling transduction have exhibited promising prospects and potential for tumor treatment. An increasing number of medications targeting this pathway are continuously being developed and validated. This comprehensive review aims to summarize the latest advances in our understanding of the role played by the Wnt/ß-catenin signaling pathway in carcinogenesis and targeted therapy, providing valuable insights into acknowledging current opportunities and challenges associated with targeting this signaling pathway in cancer research and treatment.

The Impact of Prostate Volume on Prostate Cancer Detection: Comparing Magnetic Resonance Imaging with Transrectal Ultrasound in Biopsy-naïve Men.

Background and objective: This study aimed to determine the difference in prostate volume (PV) derived from transrectal ultrasound (TRUS) and multiparametric magnetic resonance imaging (mpMRI), and to further investigate the role of TRUS prostate-specific antigen density (PSAD) and mpMRI-PSAD in prostate cancer (PCa) detection in biopsy-naïve men. Methods: Patients who underwent an initial prostate biopsy within 3 mo after mpMRI between January 2016 and December 2021 were analyzed retrospectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of both TRUS-PSAD and mpMRI-PSAD for PCa detection were calculated and compared. The Pearson correlation coefficient, Bland-Altman plot, and receiver operating characteristic curve were also utilized to explore the interests of this study. Key findings and limitations: The median prostate-specific antigen level of 875 patients was 9.79 (interquartile range [IQR]: 7.09-13.50) ng/ml. The median mpMRI-PV and TRUS-PV were 41.92 (IQR: 29.29-60.73) and 41.04 (IQR: 29.24-57.27) ml, respectively, demonstrating a strong linear correlation (r = 0.831, 95% confidence interval: 0.809, 0.850; p < 0.01) and sufficient agreement. No significant difference was observed in terms of the sensitivity, specificity, PPV, and NPV between TRUS-PSAD and mpMRI-PSAD for any PCa and clinically significant PCa (csPCa) detection. The overall discriminative ability of TRUS-PSAD for detecting PCa or non-PCa, as well as csPCa and non-csPCa, was comparable with that of mpMRI-PSAD, and similar results were also observed in the subsequent analysis stratified by mpMRI-PV quartiles, prostate-specific antigen level, and age. The limitations include the retrospective and single-center nature and a lack of follow-up information. Conclusions and clinical implications: TRUS-PV and MRI-PV exhibited a strong linear correlation and reached sufficient agreement. The efficiency of TRUS-PSAD and mpMRI-PSAD for PCa detection was comparable. TRUS could be used for PV estimation and dynamic monitoring of PSAD, and TRUS-PSAD could effectively guide clinical decision-making and optimize diagnostic strategies. Patient summary: In this work, prostate volume (PV) derived from transrectal ultrasound (TRUS) exhibited a strong linear correlation with the PV derived from multiparametric magnetic resonance imaging (mpMRI). The efficiency of TRUS prostate-specific antigen density (PSAD) and mpMRI-PSAD for the detection of prostate cancer was comparable. TRUS could be used for PV estimation and TRUS-PSAD could help in clinical decision-making and optimizing diagnostic strategies.

DNA methylation urine test in the diagnosis of upper tract urothelial carcinoma: a systematic review and meta-analysis.

OBJECTIVE: The DNA methylation urine test, a non-invasive early detection method for upper tract urothelial carcinoma (UTUC), is currently in full swing. This study aimed to systematically assess its diagnostic performance on UTUC. MATERIALS AND METHODS: PubMed, Scopus, Embase, and Cochrane were our main databases when searching articles published from January 2000 to December 2023. Sensitivity and specificity were study primary endpoints. I2 was used to evaluated heterogeneity, meanwhile subgroup and meta-regression analyses were adopted to investigated the source of heterogeneity. Sensitivity analysis was performed to evaluate the result robustness, while Deeks' funnel plot asymmetry test was for the publication bias. RESULTS: Nine studies with 1326 patients were included. The pooled sensitivity was 0.89 (95% confidence interval (CI), 0.83-0.93) and specificity were 0.91 (95% CI, 0.83-0.96). The area under the receiver operating characteristic curve was 0.96 (95% CI, 0.93-0.97). Substantial heterogeneity was found during the data synthesis, whereas the pooled results remained robust in the sensitivity analysis. None of the potential covariates-urine sample collection method, population, country, methylation test method, or tumor grade-could account for the heterogeneity. CONCLUSION: DNA methylation urine test is a promising method with high efficiency for UTUC early detection. Nevertheless, owing to the significant heterogeneity, more well-organized studies are warranted to further explore its diagnostic efficiency and application context.

Preoperative Systemic Inflammation Score Predicts the Prognosis of Patients with Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy.

Background: To investigate the prognostic significance of systemic inflammation score (SIS) in upper tract urothelial carcinoma (UTUC) in patients undergoing radical nephroureterectomy (RNU). Methods: A total of 313 UTUC patients who underwent RNU at West China Hospital from May 2014 to June 2019 were retrospectively analyzed. The predictive value of SIS for relevant endpoints, including overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS), was assessed by Kaplan-Meier curves and the Cox proportional hazards model. Results: According to inclusion and exclusion criteria, 218 UTUC patients were ultimately included in this cohort study. Statistical analysis shows that increased SIS was significantly associated with higher TNM stage (p = 0.017), lower BMI (p = 0.037), absence of hemoglobin (p < 0.001), and pathologic necrosis (p = 0.007). Kaplan-Meier survival curves clearly visually stratified survival for the three outcomes. After adjusting for tumor grade, the multivariate Cox proportional hazards model results showed that SIS was an independent risk factor for poor OS and CSS (HR = 1.89, 95% CI: 1.11-3.21, p = 0.0183, HR = 1.89, 95% CI: 1.07-3.33, p = 0.0285) in the advanced group. Conclusions: SIS was an independent risk factor for OS and CSS after RNU in patients with high-grade UTUC. It may be a novel and conducive tool for preoperative risk stratification and guiding individualized therapy for high-risk UTUC patients.

Survival impact of variant histology in patients with upper tract urothelial carcinoma after radical nephroureterectomy.

OBJECTIVE: To investigate the prognostic impact of variant histology (VH) on survival outcomes in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). MATERIALS AND METHODS: Data from 635 UTUC patients who underwent RNU at our institution from May 2003 to June 2019 were retrospectively acquired and analyzed. After propensity score matching (PSM), we investigated the impact of VH on overall survival (OS) and cancer-specific survival (CSS) by using cumulative incidence plots with the log-rank test, Cox regression models, and competing risk regression models. RESULTS: Overall, 121 (19.1%) patients were diagnosed with VH, including 68 (10.7%) with squamous cell differentiation (SCD) and 28 (4.4%) with adenocarcinoma differentiation (AD). After PSM, the presence of VH was significantly associated with worse OS (HR 1.70, 95% CI 1.25-2.32) and CSS (HR 1.64, 95% CI 1.17-2.31) only in locally advanced UTUC patients (pT>2). In the subgroup analysis, SCD revealed inferior outcomes (OS: HR 1.81, 95% CI 1.28-2.57; CSS: HR 1.73, 95% CI 1.18-2.54) compared with pure urothelial carcinoma (pUC), whereas AD conferred comparable outcomes. In addition, compared with pUC patients, SCD patients with extensive squamous components had significantly decreased OS (HR 4.17, 95% CI 1.84-9.44) and CSS (HR 1.10, 95% CI 0.61-1.99), whereas those with regional squamous components had similar survival outcomes. CONCLUSION: For UTUC patients after RNU, the presence of VH is associated with aggressive clinicopathological features and inferior survival outcomes. However, the survival outcomes of localized UTUC patients (pT≤2) with VH, and patients with the AD or regional SCD subtype are comparable to those of patients with pUC.