Prostate-specific membrane antigen-targeted surgery in prostate cancer: Accurate identification, real-time diagnosis, and precise resection.

Radical prostatectomy (RP) combined with pelvic lymph node dissection (PLND) is the first step in multimodal treatment of prostate cancer (PCa) without distant metastases. For a long time, the surgical resection range has been highly dependent on the surgeon's visualization and experience with preoperative imaging. With the rapid development of prostate-specific membrane antigen positron emission tomography and single-photon emission computed tomography (PSMA-PET and PSMA-SPECT), PSMA-targeted surgery has been introduced for a more accurate pathological diagnosis and complete resection of positive surgical margins (PSMs) and micro-lymph node metastases (LNMs). We reviewed PSMA-targeted surgeries, including PSMA-PET-guided prostatic biopsy (PSMA-TB), PSMA-targeted radio-guided surgery (PSMA-RGS), PSMA-targeted fluorescence-guided surgery (PSMA-FGS), and multi-modality/multi-targeted PSMA-targeted surgery. We also discuss the strengths and challenges of PSMA-targeted surgery, and propose that PSMA-targeted surgery could be a great addition to existing surgery protocols, thereby improving the accuracy and convenience of surgery for primary and recurrent PCa in the near future.

Macrophage-Derived Nanosponges Adsorb Cytokines and Modulate Macrophage Polarization for Renal Cell Carcinoma Immunotherapy.

Renal cell carcinoma (RCC) is a hot tumor infiltrated by large numbers of CD8+ T cells and is highly sensitive to immunotherapy. However, tumor-associated macrophages (TAMs), mainly M2 macrophages, tend to undermine the efficacy of immunotherapy and promote the progression of RCC. Here, macrophage-derived nanosponges are fabricated by M2 macrophage membrane-coated poly（lactic-co-glycolic acid）（PLGA）, which could chemotaxis to the CXC and CC chemokine subfamily-enriched RCC microenvironment via corresponding membrane chemokine receptors. Subsequently, the nanosponges act like cytokine decoys to adsorb and neutralize broad-spectrum immunosuppressive cytokines such as colony stimulating factor-1(CSF-1), transforming growth factor-ß（TGF-ß）, and Lnterleukin-10（IL-10）, thereby reversing the polarization of M2-TAMs toward the pro-inflammatory M1 phenotype, and enhancing the anti-tumor effect of CD8+ T cells. To further enhance the polarization reprogramming efficiency of TAMs, DSPE-PEG-M2pep is conjugated on the surface of macrophage-derived nanosponges for specific recognition of M2-TAMs, and the toll like receptors 7/8（TLR7/8） agonist, R848, is encapsulated in these nanosponges to induce M1 polarization, which result in significant efficacy against RCC. In addition, these nanosponges exhibit undetectable biotoxicity, making them suitable for clinical applications. In summary, a promising and facile strategy is provided for immunomodulatory therapies, which are expected to be used in the treatment of tumors, autoimmune diseases, and inflammatory diseases.

Detecting MRI-Invisible Prostate Cancers Using a Weakly Supervised Deep Learning Model.

Background: MRI is an important tool for accurate detection and targeted biopsy of prostate lesions. However, the imaging appearances of some prostate cancers are similar to those of the surrounding normal tissue on MRI, which are referred to as MRI-invisible prostate cancers (MIPCas). The detection of MIPCas remains challenging and requires extensive systematic biopsy for identification. In this study, we developed a weakly supervised UNet (WSUNet) to detect MIPCas. Methods: The study included 777 patients (training set: 600; testing set: 177), all of them underwent comprehensive prostate biopsies using an MRI-ultrasound fusion system. MIPCas were identified in MRI based on the Gleason grade (≥7) from known systematic biopsy results. Results: The WSUNet model underwent validation through systematic biopsy in the testing set with an AUC of 0.764 (95% CI: 0.728-0.798). Furthermore, WSUNet exhibited a statistically significant precision improvement of 91.3% (p < 0.01) over conventional systematic biopsy methods in the testing set. This improvement resulted in a substantial 47.6% (p < 0.01) decrease in unnecessary biopsy needles, while maintaining the same number of positively identified cores as in the original systematic biopsy. Conclusions: In conclusion, the proposed WSUNet could effectively detect MIPCas, thereby reducing unnecessary biopsies.

Endosialin in Cancer: Expression Patterns, Mechanistic Insights, and Therapeutic Approaches.

Endosialin, also known as tumor endothelial marker 1 (TEM1) or CD248, is a single transmembrane glycoprotein with a C-type lectin-like domain. Endosialin is mainly expressed in the stroma, especially in cancer-associated fibroblasts and pericytes, in most solid tumors. Endosialin is also expressed in tumor cells of most sarcomas. Endosialin can promote tumor progression through different mechanisms, such as promoting tumor cell proliferation, adhesion and migration, stimulating tumor angiogenesis, and inducing an immunosuppressive tumor microenvironment. Thus, it is considered an ideal target for cancer treatment. Several endosialin-targeted antibodies and therapeutic strategies have been developed and have shown preliminary antitumor effects. Here, we reviewed the endosialin expression pattern in different cancer types, discussed the mechanisms by which endosialin promotes tumor progression, and summarized current therapeutic strategies targeting endosialin.

Efficacy and Safety of Disitamab Vedotin Combined with Programmed Death-1 Inhibitor for Advanced Urothelial Cancer: A Case-Series Study.

INTRODUCTION: Antibody-drug conjugate (ADC) and programmed death-1 (PD-1) inhibitors play crucial roles in the treatment of advanced urothelial cancer (aUC). Increasingly, combination treatment modalities are used in patients with aUC intolerant to platinum-based chemotherapy (PBC). However, clinical evidence on the efficacy and safety of disitamab vedotin plus PD-1 inhibitors for aUC is limited. This case series aims to address this knowledge gap. METHODS: Patients with aUC who were refractory or intolerant to PBC were included. All patients received combined treatment with disitamab vedotin (one of the ADC drugs) and PD-1 inhibitors for at least three cycles. The clinical characteristics of examination, histopathology, outcomes, and adverse events (AEs) were retrospectively collected. RESULTS: Among this case series, eight patients received disitamab vedotin plus PD-1 inhibitors, of which three achieved a complete response (CR) and two had a partial response (PR). The most common AE was peripheral neuropathy (4/8); the remaining AEs were mostly of mild to moderate severity or unknown and were manageable by supportive care. CONCLUSIONS: Disitamab vedotin combined with PD-1 inhibitors exhibits a favorable efficacy and safety profile, but subsequent larger cohort clinical studies are required to provide evidence-based medicine for the universal application of this regimen.

Avoiding unnecessary biopsy: the combination of PRIMARY score with prostate-specific antigen density for prostate biopsy decision.

BACKGROUND: Avoiding unnecessary biopsies for men with suspected prostate cancer remains a clinical priority. The recently proposed PRIMARY score improves diagnostic accuracy in detecting clinically significant prostate cancer (csPCa). The aim of this study was to determine the best strategy combining PRIMARY score or MRI reporting scores (Prostate Imaging Reporting and Data System [PI-RADS]) with prostate-specific antigen density (PSAD) for prostate biopsy decision making. METHODS: A retrospective analysis of 343 patients who underwent both 68Ga-PSMA PET/CT and MRI before prostate biopsy was performed. PSA was restricted to <20 ng/ml. Different biopsy strategies were developed and compared based on PRIMARY score or PI-RADS with PSAD thresholds. Decision curve analysis (DCA) was plotted to define the optimal biopsy strategy. RESULTS: The prevalence of csPCa was 41.1% (141/343). According to DCA, the strategies of PRIMARY score +PSAD (strategy #1, strategy #2, strategy #6) had a higher net benefit than the strategies of PI-RADS + PSAD at the risk threshold of 8-20%. The best diagnostic strategy was strategy #1 (PRIMARY score 4-5 or PSAD ≥ 0.20), which avoided 38.2% biopsy procedures while missed 9.2% of csPCa cases. From a clinical perspective, strategies with a lower risk of missing csPCa were strategy #2 (PRIMARY score ≥4 or PSAD ≥ 0.15), which avoided 28.6% biopsies while missed 5.7% of csPCa cases, or strategy #6 (PRIMARY score≥3 or PSAD ≥ 0.15), which avoided 20.7% biopsies while missed only 3.5% of csPCa cases. The limitations of the study were the retrospective single-center nature. CONCLUSIONS: The combination of PRIMARY score +PSAD allows individualized decisions to avoid unnecessary biopsy, outperforming the strategies of PI-RADS + PSAD. Further prospective trials are needed to validate these findings.

The PRIMARY Score: Diagnostic Performance and Added Value Compared With MRI in Detecting Clinically Significant Prostate Cancer.

PURPOSE: Multiparametric MRI is the current standard for detecting clinically significant prostate cancer (csPCa). However, men with negative or equivocal MRI often undergo unnecessary biopsies due to concerns about false-negative results. The recently proposed 68 Ga-PSMA PET/CT-based PRIMARY score exhibited good diagnostic performance for csPCa. This study aimed to externally validate the performance of the PRIMARY score and evaluate its added diagnostic value to MRI triage in detecting csPCa. PATIENTS AND METHODS: This retrospective cohort study included 431 men who underwent both 68 Ga-PSMA PET/CT and MRI before biopsy. Performance was assessed using the area under the receiver operating characteristic curve and the decision curve analysis. The PRIMARY score + MRI was considered positive for either PRIMARY score 3-5 or Prostate Imaging Reporting and Data System (PI-RADS) 4/5. RESULTS: The prevalence of csPCa was 51.7% (223/431). The area under the receiver operating characteristic curve of the 5-level PRIMARY score for csPCa was significantly higher than that of MRI (0.873 vs 0.786, P < 0.001). For the entire group, sensitivity, specificity, positive predictive value, and negative predictive value of the PRIMARY score were 90.6%, 61.1%, 71.4%, and 85.8%, respectively, which outperformed 87.9%, 49.0%, 64.9%, and 79.1% of PI-RADS on MRI. The PRIAMRY score + MRI improved sensitivity (96.0% vs 87.9%, P < 0.001) and negative predictive value (91.5% vs 79.1%, P < 0.001) without compromising specificity and positive predictive value compared with MRI alone. This combined approach avoided 24.6% (106/431) of unnecessary biopsies, while missing 4.0% (9/223) of csPCa cases. The addition of the PRIMARY score in men with PI-RADS 1-3 showed a net benefit, but not in men with PI-RADS 4/5. CONCLUSIONS: The PRIMARY score was superior to MRI in detecting csPCa, and its added diagnostic value was in men with negative or equivocal MRI results. The PRIMARY score + MRI improved negative predictive value and sensitivity for csPCa compared with MRI alone. Further prospective trials will validate whether men with clinical suspicion of csPCa but negative PRIMARY score + MRI can safely avoid unnecessary biopsies.

Reoperation after surgical treatment for benign prostatic hyperplasia: a systematic review.

Context: Surgical treatment is important for male lower urinary tract symptom (LUTS) management, but there are few reviews of the risks of reoperation. Objective: To systematically evaluate the current evidence regarding the reoperation rates of surgical treatment for LUTS in accordance with current recommendations and guidelines. Evidence acquisition: Eligible studies published up to July 2023, were searched for in the PubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), and Web of Science™ (Clarivate™, Philadelphia, PA, USA) databases. STATA® (StataCorp LP, College Station, TX, USA) software was used to conduct the meta-analysis. Random-effects models were used to calculate the pooled incidences (PIs) of reoperation and the 95% confidence intervals (CIs). Evidence synthesis: A total of 119 studies with 130,106 patients were included. The reoperation rate of transurethral resection of the prostate (TURP) at 1, 2, 3, and 5 years was 4.0%, 5.0%, 6.0%, and 7.7%, respectively. The reoperation rate of plasma kinetic loop resection of the prostate (PKRP) at 1, 2, 3, and 5 years was 3.5%, 3.6%, 5.7%, and 6.6%, respectively. The reoperation rate of holmium laser enucleation of the prostate (HoLEP) at 1, 2, 3, and 5 years was 2.4%, 3.3%, 5.4%, and 6.6%, respectively. The reoperation rate of photoselective vaporization of the prostate (PVP) at 1, 2, 3, and 5 years was 3.3%, 4.1%, 6.7%, and 7.1%, respectively. The reoperation rate of surgery with AquaBeam® at 1, 2, 3, and 5 years was 2.6%, 3.1%, 3.0%, and 4.1%, respectively. The reoperation rate of prostatic artery embolization (PAE) at 1, 2, 3, and 5 years was 12.2%, 20.0%, 26.4%, and 23.8%, respectively. The reoperation rate of transurethral microwave thermotherapy (TUMT) at 1, 2, 3, and 5 years was 9.9%, 19.9%, 23.3%, and 31.2%, respectively. The reoperation rate of transurethral incision of the prostate (TUIP) at 5 years was 13.4%. The reoperation rate of open prostatectomy (OP) at 1 and 5 years was 1.3% and 4.4%, respectively. The reoperation rate of thulium laser enucleation of the prostate (ThuLEP) at 1, 2, and 5 years was 3.7%, 7.7%, and 8.4%, respectively. Conclusion: Our results summarized the reoperation rates of 10 surgical procedures over follow-up durations of 1, 2, 3, and 5 years, which could provide reference for urologists and LUTS patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023445780.

Small Mitochondria-Targeting Fluorophore with Multifunctional Therapeutic Activities against Prostate Cancer via the HIF1α/OATPs Pathway.

Prostate cancer (PCa) is considered to be the most prevalent malignancy in males worldwide. Abiraterone is a 17α-hydroxylase/C17, 20-lyase (CYP17) inhibitor that has been approved for use in patients with prostate cancer. However, several negative aspects, such as drug resistance, toxicity, and lack of real-time monitoring of treatment responses, could appear with long-term use. Therefore, the development of anticancer agents with specific targeting to avoid side effects is imperative. Here, we used MHI-148, a type of heptamethine cyanine (HC) near-infrared fluorescence dye (NIRF), as a prototype structure to synthesize two theranostic agents, Abi-DZ-1 and Abi-783. The new compound Abi-DZ-1 retained the excellent photophysical characteristics and NIRF imaging property of MHI-148, and it could preferentially accumulate in prostate cancer cells but not in normal prostate epithelial cells via the HIF1α/organic anion-transporting polypeptides axis. NIRF imaging using Abi-DZ-1 selectively identified tumors in mice bearing PCa xenografts. Moreover, Abi-DZ-1 treatment significantly retarded the tumor growth in both a cell-derived xenograft model and a patient-derived tumor xenograft model. This finding demonstrated that Abi-DZ-1 may hold promise as a potential multifunctional theranostic agent for future tumor-targeted imaging and precision therapy. Constructing theranostic agents using the NIRF dye platform holds great promise in accurate therapy and intraoperative navigation.

Effects of Lentilactobacillus buchneri and Kazachstania bulderi on the Quality and Flavor of Guizhou Fermented Red Sour Soup.

In this study, the effects of Lentilactobacillus buchneri (L. buchneri: CCTCC M 2023228) and Kazachstania bulderi (K. bulderi: CCTCC M 2023227) on the quality characteristics and volatile flavor substances in fermented red sour soup were explored based on natural fermentation. Compared to natural fermentation (nitrite: 5.5 mg/kg; amino acid nitrogen: 0.17 g/100 g; lycopene: 63.73 µg/mL), three fortified fermentation methods using L. buchneri, K. bulderi, and both strains together significantly reduced the concentrations of nitrite (2.62, 2.49, and 2.37 mg/kg), amino acid nitrogen (0.03 g/100 g, 0.02 g/100 g, and 0.05 g/100 g), and lycopene (26.64, 32.45, and 51.89 µg/mL). Total acid content (11.53 g/kg) and lactic acid bacteria count (285.9 ± 1.65 × 106 CFU/mL) were the elements most significantly increased by fortified fermentation with L. buchneri relative to other fermentation methods. A total of 99 volatile compounds were determined in red sour soup and could be roughly classified into alcohols, aldehydes, ketones, and esters. Fortified fermentation with two strains and fortified fermentation with K. bulderi increased the content of methyl butanoate and 3-hydroxybutan-2-one-acetoin (D). This study confirmed the effects of L. buchneri and K. bulderi on the quality and flavor of fermented red sour soup and provided a theoretical basis for the fortified fermentation of red sour soup.

A Prostate-Specific Membrane Antigen PET-Based Approach for Improved Diagnosis of Prostate Cancer in Gleason Grade Group 1: A Multicenter Retrospective Study.

The preoperative Gleason grade group (GG) from transrectal ultrasound-guided prostate biopsy is crucial for treatment decisions but may underestimate the postoperative GG and miss clinically significant prostate cancer (csPCa), particularly in patients with biopsy GG1. In such patients, an SUVmax of at least 12 has 100% specificity for detecting csPCa. In patients with an SUVmax of less than 12, we aimed to develop a model to improve the diagnostic accuracy of csPCa. Methods: The study retrospectively included 56 prostate cancer patients with transrectal ultrasound-guided biopsy GG1 and an SUVmax of less than 12 from 2 tertiary hospitals. All [68Ga]Ga-PSMA-HBED-CC PET scans were centrally reviewed in Xijing Hospital. A deep learning model was used to evaluate the overlap of SUVmax (size scale, 3 cm) and the level of Gleason pattern (size scale, 500 µm). A diagnostic model was developed using the PRIMARY score and SUVmax, and its discriminative performance and clinical utility were compared with other methods. The 5-fold cross-validation (repeated 1,000 times) was used for internal validation. Results: In patients with GG1 and an SUVmax of less than 12, significant prostate-specific membrane antigen (PSMA) histochemical score (H-score) H-score overlap occurred among benign gland, Gleason pattern 3, and Gleason pattern 4 lesions, causing SUVmax overlap between csPCa and non-csPCa. The model of 10 × PRIMARY score + 2 × SUVmax exhibited a higher area under the curve (AUC, 0.8359; 95% CI, 0.7233-0.9484) than that found using only the SUVmax (AUC, 0.7353; P = 0.048) or PRIMARY score (AUC, 0.7257; P = 0.009) for the cohort and a higher AUC (0.8364; 95% CI, 0.7114-0.9614) than that found using only the Prostate Imaging Reporting and Data System (PI-RADS) score of 5-4 versus 3-1 (AUC, 0.7036; P = 0.149) and the PI-RADS score of 5-3 versus 2-1 (AUC, 0.6373; P = 0.014) for a subgroup. The model reduced the misdiagnosis of the PI-RADS score of 5-4 versus 3-1 by 78.57% (11/14) and the PI-RADS score of 5-3 versus 2-1 by 77.78% (14/18). The internal validation showed that the mean 5-fold cross-validated AUC was 0.8357 (95% CI, 0.8357-0.8358). Conclusion: We preliminarily suggest that the model of 10 × PRIMARY score + 2 × SUVmax may enhance the diagnostic accuracy of csPCa in patients with biopsy GG1 and an SUVmax of less than 12 by maximizing PSMA information use, reducing the misdiagnosis of the PI-RADS score, and thereby aiding in making appropriate treatment decisions.

[Research Progress in Preoperative Evaluation of Lymph Node Metastasis of Bladder Cancer].

Bladder cancer is a common malignant tumor of the urinary system.The prognosis of patients with positive lymph nodes is worse than that of patients with negative lymph nodes.An accurate assessment of preoperative lymph node statushelps to make treatmentdecisions,such as the extent of pelvic lymphadenectomy and the use of neoadjuvant chemotherapy.Imaging examination and pathological examination are the primary methods used to assess the lymph node status of bladder cancer patients before surgery.However,these methods have low sensitivity and may lead to inaccuate staging of patients.We reviewed the research progress and made an outlook on the application of clinical diagnosis,imaging techniques,radiomics,and genomics in the preoperative evaluation of lymph node metastasis in bladder cancer patients at different stages.

PI-RADS-Based Segmented Threshold of PSMA-PET SUVmax Is Better than Traditional Fixed Threshold for Diagnosing Clinically Significant Prostate Cancer Especially for PI-RADS 3 Lesions.

OBJECTIVES: Our purpose was to compare the performance of prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) traditional fixed threshold (FT) and newly established Prostate Imaging Reporting and Data System (PI-RADS)-based segmented threshold (ST) for diagnosing clinically significant prostate cancer (csPCa). METHODS: The study retrospectively included 218 patients who underwent multiparametric magnetic resonance imaging (mpMRI) and PSMA-PET examination for suspected prostate cancer (PCa) from January 2018 to November 2021. Lesions with Gleason score ≥ 3 + 4 were diagnosed as csPCa. In PSMA-PET maximum standardized uptake value (SUVmax), the FT for all the lesions and STs for lesions with different PI-RADS score for diagnosing csPCa were determined by receiver operating characteristic (ROC) curves analysis and compared with Z test. The McNemar test was used to compare sensitivity and specificity. RESULTS: Among the 218 patients, there were 113 csPCa and 105 non-csPCa. The PSMA-PET FT was SUVmax > 5.3 (area under the curve, AUC = 0.842) and STs for PI-RADS 3/4/5 were SUVmax > 4.2/5.7/6.0 (AUCs = 0.870/0.867/0.882), respectively. The AUC of PSMA-PET ST was higher than that of PSMA-PET FT (0.872 vs. 0.842), especially for PI-RADS 3 (0.870 vs. 0.653). Multimodality diagnostic criteria combining PSMA-PET ST and PI-RADS scores of mpMRI was established and its AUC was higher than that of PSMA-PET ST (0.893 vs. 0.872) and significantly higher than that of PSMA-PET FT (0.893 vs. 0.842) with an improvement in sensitivity (93% vs. 78%, p < 0.05) without significantly sacrificing specificity (86% vs. 91%, p > 0.05). CONCLUSIONS: For diagnosing csPCa, PI-RADS-based PSMA-PET segmented threshold achieved better performance than traditional fixed threshold, especially for PI-RADS 3 lesions. Multimodality diagnostic criteria demonstrated higher diagnostic performance than segmented threshold and significantly better than PSMA-PET fixed threshold for detecting csPCa.

The combination of NDUFS1 with CD4+ T cell infiltration predicts favorable prognosis in kidney renal clear cell carcinoma.

Background: Kidney renal clear cell carcinoma (KIRC) is an immunogenic tumor, and immune infiltrates are relevant to patients' therapeutic response and prognosis. NDUFS1, the core subunit of mitochondrial complex I, has been reported to be associated with KIRC patients' prognosis. However, the upstream regulator for NDUFS1 and their correlations with immune infiltration remain unclear. Methods: The expression of NDUFS genes in KIRC and their influences on patients' survival were investigated by UALCAN, ENCORI, Oncomine, TIMER as well as Kaplan-Meier Plotter. miRNAs regulating NDUFS1 were predicted and analyzed by TargetScan and ENCORI. The correlations between NDUFS1 expression and immune cell infiltration or gene marker sets of immune infiltrates were analyzed via TIMER. The overall survival in high/low NDUFS1 or hsa-miR-320b expressed KIRC patients with or without immune infiltrates were analyzed via Kaplan-Meier Plotter. The combined NDUFS1 expression and/or CD4+ T cell infiltration on KIRC patients' overall survival were validated by multiplexed immunofluorescence (mIF) staining in tissue microarray (TMA). Furthermore, the influences of NDUFS1 expression on the chemotaxis of CD4+ T cells to KIRC cells were performed by transwell migration assays. Results: We found that the low expression of NDUFS1 mRNA and protein in KIRC was correlated with unfavorable patients' survival and poor infiltration of CD4+ T cells. In patients with decreased CD4+ T cell infiltration whose pathological grade less than III, TMA mIF staining showed that low expression of NDUFS1 had significantly poor OS than that with high expression of NDUFS1 did. Furthermore, hsa-miR-320b, a possible negative regulator of NDUFS1, was highly expressed in KIRC. And, low NDUFS1 or high hsa-miR-320b consistently correlated to unfavorable outcomes in KIRC patients with decreased CD4+ T cell infiltration. In vitro, NDUFS1 overexpression significantly increased the chemotaxis of CD4+ T cell to KIRC cells. Conclusion: Together, NDUFS1, upregulated by decreased hsa-miR-320b expression in KIRC patients, might act as a biomarker for CD4+ T cell infiltration. And, the combination of NDUFS1 with CD4+ T cell infiltration predicts favorable prognosis in KIRC.

Comparison of prostate volume measured by transabdominal ultrasound and MRI with the radical prostatectomy specimen volume: a retrospective observational study.

BACKGROUND: Few studies have compared the use of transabdominal ultrasound (TAUS) and magnetic resonance imaging (MRI) to measure prostate volume (PV). In this study, we evaluate the accuracy and reliability of PV measured by TAUS and MRI. METHODS: A total of 106 patients who underwent TAUS and MRI prior to radical prostatectomy were retrospectively analyzed. The TAUS-based and MRI-based PV were calculated using the ellipsoid formula. The specimen volume measured by the water-displacement method was used as a reference standard. Correlation analysis and intraclass correlation coefficients (ICC) were performed to compare different measurement methods and Bland Altman plots were drawn to assess the agreement. RESULTS: There was a high degree of correlation and agreement between the specimen volume and PV measured with TAUS (r = 0.838, p < 0.01; ICC = 0.83) and MRI (r = 0.914, p < 0.01; ICC = 0.90). TAUS overestimated specimen volume by 2.4ml, but the difference was independent of specimen volume (p = 0.19). MRI underestimated specimen volume by 1.7ml, the direction and magnitude of the difference varied with specimen volume (p < 0.01). The percentage error of PV measured by TAUS and MRI was within ± 20% in 65/106(61%) and 87/106(82%), respectively. In patients with PV greater than 50 ml, MRI volume still correlated strongly with specimen volume (r = 0.837, p < 0.01), while TAUS volume showed only moderate correlation with specimen (r = 0.665, p < 0.01) or MRI volume (r = 0.678, p < 0.01). CONCLUSIONS: This study demonstrated that PV measured by MRI and TAUS is highly correlated and reliable with the specimen volume. MRI might be a more appropriate choice for measuring the large prostate.

Unambiguous radiologic extranodal extension determined by MRI could be a biomarker in predicting metastatic prostate cancer.

OBJECTIVE: To explore the relationship between unambiguous radiologic extranodal extension (rENE) and M1 staging in patients with metastatic PCa. METHODS: A respective analysis of 1073 patients of PCa N1 staging from January 2004 to May 2022 was retrospectively enrolled. They were divided into rENE + and rENE - groups and retrospectively analyzed the M staging with nuclear medicine data. The correlation index between unambiguous rENE and M1b staging was calculated. Logistic regression was used to evaluate the predictive performance of unambiguous rENE in M1b staging. ROC curves were used to investigate the relationship between unambiguous rENE and M staging in patients who underwent 68 Ga-PSMA PET/CT. RESULTS: A total of 1073 patients were included. Seven hundred and eighty patients were classified into the rENE + group (mean age, 69.6 years ± 8.7 [standard deviation]), and 293 were classified into rENE - group (mean age, 66.7 years ± 9.4 [standard deviation]). Relationship between unambiguous rENE and M1b existed (r = 0.58, 95%CI: 0.52-0.64, P < 0.05). Unambiguous rENE could be an independent predictor for M1b (OR = 13.64, 95%CI: 9.23-20.14, P < 0.05). The AUC of unambiguous rENE in predicting M1b and M staging was 0.835 and 0.915, respectively, in patients who underwent 68 Ga-PSMA PET/CT. CONCLUSIONS: Unambiguous rENE could be a strong biomarker to predict M1b and M staging in patients with PCa. When rENE came up, patients should perform nuclear medicine immediately, and a systematic treatment should be considered.

CD248 promotes migration and metastasis of osteosarcoma through ITGB1-mediated FAK-paxillin pathway activation.

BACKGROUND: Osteosarcoma (OS) is the most common malignant bone tumor with a high incidence in children and adolescents. Frequent tumor metastasis and high postoperative recurrence are the most common challenges in OS. However, detailed mechanism is largely unknown. METHODS: We examined the expression of CD248 in OS tissue microarrays by immunohistochemistry (IHC) staining. We studied the biological function of CD248 in cell proliferation, invasion and migration of OS cells by CCK8 assay, transwell and wound healing assay. We also studied its function in the metastasis of OS in vivo. At last, we explored the potential mechanism how CD248 promotes OS metastasis by using RNA-seq, western blot, immunofluorescence staining and co-immunoprecipitation using CD248 knockdown OS cells. RESULTS: CD248 was highly expressed in OS tissues and its high expression was correlated with pulmonary metastasis of OS. Knockdown of CD248 in OS cells significantly inhibited cell migration, invasion and metastasis, while had no obvious effect on cell proliferation. Lung metastasis in nude mice was significantly inhibited when CD248 was knocked down. Mechanistically, we found that CD248 could promote the interaction between ITGB1 and extracellular matrix (ECM) proteins like CYR61 and FN, which activated the FAK-paxillin pathway to promote the formation of focal adhesion and metastasis of OS. CONCLUSION: Our data showed that high CD248 expression is correlated with the metastatic potential of OS. CD248 may promote migration and metastasis through enhancing the interaction between ITGB1 and certain ECM proteins. Therefore, CD248 is a potential marker for diagnosis and effective target for the treatment of metastatic OS.

NPAS2 promotes aerobic glycolysis and tumor growth in prostate cancer through HIF-1A signaling.

BACKGROUND: Prostate cancer (PCa), one of the common malignant tumors, is the second leading cause of cancer-related deaths in men. The circadian rhythm plays a critical role in disease. Circadian disturbances are often found in patients with tumors and enable to promote tumor development and accelerate its progression. Accumulating evidence suggests that the core clock gene NPAS2 (neuronal PAS domain-containing protein 2) has been implicated in tumors initiation and progression. However, there are few studies on the association between NPAS2 and prostate cancer. The purpose of this paper is to investigate the impact of NPAS2 on cell growth and glucose metabolism in prostate cancer. METHODS: Quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) staining, western blot, GEO (Gene Expression Omnibus) and CCLE (Cancer Cell Line Encyclopedia) databases were used to analyze the expression of NPAS2 in human PCa tissues and various PCa cell lines. Cell proliferation was assessed using MTS, clonogenic assays, apoptotic analyses, and subcutaneous tumor formation experiments in nude mice. Glucose uptake, lactate production, cellular oxygen consumption rate and medium pH were measured to examine the effect of NPAS2 on glucose metabolism. The relation of NPAS2 and glycolytic genes was analyzed based on TCGA (The Cancer Genome Atlas) database. RESULTS: Our data showed that NPAS2 expression in prostate cancer patient tissue was elevated compared with that in normal prostate tissue. NPAS2 knockdown inhibited cell proliferation and promoted cell apoptosis in vitro and suppressed tumor growth in a nude mouse model in vivo. NPAS2 knockdown led to glucose uptake and lactate production diminished, oxygen consumption rate and pH elevated. NPAS2 increased HIF-1A (hypoxia-inducible factor-1A) expression, leading to enhanced glycolytic metabolism. There was a positive correlation with the expression of NPAS2 and glycolytic genes, these genes were upregulated with overexpression of NPAS2 while knockdown of NPAS2 led to a lower level. CONCLUSION: NPAS2 is upregulated in prostate cancer and promotes cell survival by promoting glycolysis and inhibiting oxidative phosphorylation in PCa cells.

Percutaneous nephroscopy combined with the laser used for right kidney bullet extraction: A case report.

RATIONALE: Wounds caused by firearms are intractable problems in treating war traumas and clinical management. Conventional open surgery inflicts large injury and leads to slow recovery. At the same time, most patients suffer from compound injuries with the critical condition and poor operation tolerance. Thus, it is crucial to probe into the minimally invasive surgical removal of residual kidney bullets. PATIENT CONCERNS: We report a case where a bullet remained in the right renal parenchyma on the patient, with penetrating injury in his liver. DIAGNOSIS: Obviously the patient has suffered gunshot wound with a bullet stuck in his kidney, while his liver function was impacted. INTERVENTIONS: Six months after the injury, we performed the minimally-invasive procedures on the patient with percutaneous nephroscope technology and laser technology under the guidance of ultrasound localization. The bullet and ammunition granulation and scar surrounding tissue were fully removed. Intraoperative bleeding was little, while the incision was small. The patient could leave the bed and walk on the 1st postoperative day. The drainage tube was removed on the 3rd postoperative day, after which the patient was discharged on the 4th postoperative day. OUTCOMES: The patient recovered well after surgery and was followed up for 5 years. The latest examination of his liver and kidney function was as follows: alanine aminotransferase 61IU/L, aspartate aminotransferase 33 IU/L, albumin/globulin 46.6/26.0, total bilirubin 19.1µmol/L, direct bilirubin 4.9µmol/L, indirect bilirubin 14.2µmol/L, alkaline phosphatase 111 IU/L, creatinine 57µmol/L, urea 5.16mmol/L, cystatin 0.73mg/L. The plain computed tomography scan showed a few calcifications in the liver and a patchy low-density shadow in the right kidney. It was proved that the liver and kidney function of the patient recovered well, and his living qualify has come back to the track, with no postoperative complications. LESSONS: Innovative integration of percutaneous nephroscopy technology and laser was used to remove kidney foreign bodies and developed the optimal surgical plan, small trauma, fast recovery, and the treatment of kidney foreign bodies was newly explored.