AP-2α gene deregulation is associated with renal cell carcinoma patient survival.

BACKGROUND: Renal cell carcinoma (RCC), one of the most fatal urologic tumors, accounts for approximately 3% of all adult cancers and exhibits a high metastatic index at diagnosis and a high rate of relapse. Radical or partial nephrectomy is a curative option for nonmetastatic RCCs. Targeted therapy has been shown to improve the survival of patients with metastatic RCCs. However, the underlying cellular and molecular events associated with RCC pathogenesis are not well known. METHODS: To investigate the clinical role of the transcription factor activator protein (AP)-2α in RCC, methylated CpG island recovery assays and microarray analysis were employed. COBRA and RT‒qPCR assays were performed to assess AP-2α expression in RCC. RESULTS: A negative correlation was noted between AP-2α mRNA expression levels and methylation status. Multivariate analyses showed that AP-2α mRNA was a major risk factor not only for overall and disease-free survival in RCC but also for disease-free survival in clear cell RCC. CONCLUSIONS: Our results indicated that AP-2α expression was deregulated in RCC and associated with overall patient survival and disease-free survival. Such findings suggest that AP-2α might play an important role in the pathogenesis of RCC.

Integrating clinical and image-based parameters for prediction of early post-prostatectomy incontinence recovery: simplified nomogram approach.

PURPOSE: This study aimed to develop a novel model that combines both clinical and image-based parameters to predict early recovery of urinary incontinence after robotic-assisted radical prostatectomy (RARP) more easily and precisely. MATERIALS AND METHODS: We retrospectively enrolled data from patients who underwent RARP performed by a single surgeon. Clinical parameters were collected through medical chart review. All patients received cystography one week after RARP to evaluate the anastomosis healing condition. All cystography images were analyzed by a single radiologist who was blinded to the clinical status of the patients. Multivariate analysis was performed to select significant predictors for early post-prostatectomy incontinence (PPI) recovery, defined as being pad-free within four weeks after surgery. RESULTS: A total of 293 patients were enrolled in this study. Among them, 26.7% experienced immediate dryness after surgery, while 47.6% achieved being pad-free within one month. The overall continence rate was over 90% six months after surgery. In univariate analysis, factors associated with early PPI recovery were BMI, T stage, NVB preservation, surgical margin status, downward bladder neck, and bladder neck angle on cystography. BMI, NVB preservation, and downward bladder neck remained significant in multivariate analysis (p-values = 0.041, 0.027, and 0.023, respectively). A nomogram model was established based on these three predictors. CONCLUSION: This is the first model to combine preoperative clinical factors, peri-surgical factors, and postoperative image-based factors to predict PPI recovery after RARP. This model can assist clinicians in taking optimal actions for PPI and also reduce patient anxiety.

Long-term use and risk of major adverse cardiac events: Comparing enzalutamide and abiraterone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer.

This is a retrospective cohort study by analyzing a multi-institutional electronic medical records database in Taiwan to compare long-term effectiveness and risk of major adverse cardiac events (MACE) in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients treated with enzalutamide (ENZ) or abiraterone (AA). Patients aged 20 years and older and newly receiving androgen receptor targeted therapies ENZ or AA from September 2016 to December 2019 were included. We followed patients from initiation of therapies to the occurrence of outcomes (prostate-specific antigen (PSA) response rate, PSA progression free survival (PFS), overall survival (OS), and MACE), death, the last clinical visit, or December 31, 2020. We performed multivariable Cox proportional hazard models to compare ENZ and AA groups for the measured outcomes. A total of 363 patients treated with either ENZ (n = 157) or AA (n = 206) were identified. The analysis found a significantly higher proportion of patients with a PSA response rate higher than 50% among those receiving ENZ than among those receiving AA (ENZ vs AA: 75.80% vs 63.59%, P = .01). However, there was no significant difference in PSA PFS (adjusted hazard ratio: 0.86; 95% CI 0.63-1.17) and OS (0.68: 0.41-1.14) between the use of ENZ and AA in chemotherapy-naïve mCRPC patients. Regarding the cardiovascular (CV) safety outcome, there was a significantly lower risk of MACE in patients receiving ENZ, compared to patients receiving AA (0.20: 0.07-0.55). The findings suggest that enzalutamide may be more efficacious for PSA response and suitable for chemotherapy-naïve mCRPC patients with high CV risk profile.

Should Patients with Renal Cell Carcinoma and Pathological Nodal Invasion Be Classified As Having Stage IV Disease?

BACKGROUND: Lymph node invasion is associated with poor outcome in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients with RCC within a single center from 2001 to 2018 were retrospectively obtained from the Chang Gung Research Database. Patient gender, physical status, Charlson Comorbidity Index, tumor side, histology, age at diagnosis, and body mass index (BMI) were compared. The overall survival (OS) and cancer-specific survival (CSS) of each group were estimated using the Kaplan-Meier method. Log-rank tests were used to compare between the subgroups. RESULTS AND CONCLUSIONS: A total of 335 patients were enrolled, of whom 76 had pT3N0M0, 29 had pT1-3N1M0, 104 had T1-4N0M1, and 126 had T1-4N1M1 disease. Significant OS difference was noted between pT3N0M0 and pT1-3N1M0 groups with 12.08 years [95% confidence interval (CI), 8.33-15.84] versus 2.58 years (95% CI, 1.32-3.85), respectively (P < 0.005). No significant difference was observed in OS between pT1-3N1M0 and T1-4N0M1 groups with 2.58 years (95% CI, 1.32-3.85) versus 2.50 years (95% CI, 1.85-3.15, P = 0.72). The OS of N1M1 group was worse than that of N0M1 group with 1.00 year (95% CI, 0.74-1.26) versus 2.50 years (95% CI, 1.85-3.15, P < 0.05). Similar results were also observed in CSS. In summary, we claim that RCC with lymph node (LN) invasion should be reclassified as stage IV disease in terms of survival outcome.

Development and assessment of a self-management intervention for urinary incontinence among patients with prostate cancer: protocol for a randomized feasibility study.

BACKGROUND: Urinary incontinence is a common complication among patients with prostate cancer who have undergone radical prostatectomy. Guided by social cognitive theory and a framework for the recovery of health and well-being, we propose to develop and test a self-management intervention for patients with prostate cancer who experience urinary incontinence after undergoing radical prostatectomy. METHODS: In this study, a self-management intervention for urinary incontinence (SMI-UI) is developed, comprising a mobile self-management application, a self-management handbook, and professional support. The feasibility, acceptability, and effectiveness of this intervention will be assessed. Patient data from the urology departments of two hospitals will be collected through convenience sampling by adopting an experimental, parallel, and random assignment research design. Patients experiencing urinary incontinence after undergoing radical prostatectomy will be invited to participate. After completing the pretest questionnaire, patients will be randomly divided into the experimental and attention control groups. The experimental group will undergo a 12-week SMI-UI, whereas the attention control group will receive an intervention consisting of a single dietetic education information package. The two groups will be tested 12 and 16 weeks after the pretest. In this study, we recorded the sociodemographic and clinical variables; recruitment rate; retention rate; satisfaction with the intervention; cancer-related self-efficacy; urination symptoms and disturbance; social participation and satisfaction; resilience; and demoralization. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05335967 [date of registration 04-04-2022].

Is decompressive craniectomy necessary in malignant posterior reversible encephalopathy syndrome with brain edema caused uncal herniation? A case report of reversible coma without surgical decompression.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is considered a benign entity and is usually reversible with only medical management, but persistent neurologic deficits and disability or death can occur without adequate treatment. Favorable outcomes have been associated with surgical decompression in malignant-type PRES in which hemorrhagic transformation or brain stem compression has developed. CASE DESCRIPTION: Here we report a case of malignant PRES in a 61-year-old female of Asian descent in which the disease rapidly progressed to coma and a near-fatal condition with uncal herniation caused by severe brain edema; however, this patient achieved a dramatic recovery without surgical decompression. CONCLUSION: After reviewing previous reports regarding malignant PRES, we propose that hemorrhagic transformation is a crucial indicator for surgical decompression and an important prognostic factor in malignant PRES.

Emotional state and cancer-related self-efficacy as affecting resilience and quality of life in kidney cancer patients: a cross-sectional study.

OBJECTIVE: To assess the relationship between resilience and quality of life (QOL) of kidney cancer patients, including influencing factors. METHODS: Based on a cross-sectional study design, participants (N = 103) were recruited from patients who were admitted to the urology clinic of a medical center in Taiwan between April 2020 and January 2021. Data collection was accomplished via a questionnaire. The study variables included demographic information, disease attributes, happiness level, depression, cancer-related self-efficacy, resilience, and QOL. One-way analysis of variance, Pearson correlation coefficients, independent-sample t-tests, hierarchical regression, and process analysis were the statistical methods used to analyze the data. RESULTS: Kidney cancer patients who were less depressed exhibited better cancer-related self-efficacy and have better resilience. In non-depressed individuals, higher levels of happiness and better resilience resulted in better QOL. Resilience is a mediator that affects the relationship between depression and QOL. CONCLUSIONS: Patients with better emotional state experience better resilience and QOL. Patients' better cancer-related self-efficacy is related to better resilience while better resilience is associated with better QOL. Clinical care providers need to evaluate and improve cancer-related self-efficacy, emotional state, and resilience of kidney cancer patients, which will improve their resilience and QOL.

Exploring psychological resilience and demoralisation in prostate cancer survivors.

OBJECTIVE: This study aimed to investigate psychological resilience and demoralisation and their predictors and mediators in prostate cancer survivors (PCSs). METHODS: A cross-sectional research design was used. PCSs (N = 122; mean time since diagnosis = 54.79 months, range in 13 years and 2 months) were recruited using convenience sampling at the outpatient department of a hospital in Taiwan. Data collection was conducted using self-report structured questionnaires, including one for demographic and disease characteristics, the Expanded Prostate Cancer Index Composite, Cancer Survivors' Self-Efficacy Scale, Connor-Davidson Resilience Scale and the Demoralisation Scale. RESULTS: In PCSs, a lower most-recent level of prostate-specific antigen and higher cancer-specific self-efficacy were associated with better psychological resilience. Further, fewer hormonal, bowel and urinary symptoms and bother; higher cancer-specific self-efficacy; and better psychological resilience were associated with less demoralisation. Cancer-specific self-efficacy was a mediator for the relationship between urinary symptoms and bother and demoralisation, while psychological resilience mediated the relationship between cancer-specific self-efficacy and demoralisation. CONCLUSIONS: The results reveal that cancer-specific self-efficacy is a protective factor against demoralisation and increases psychological resilience in PCSs. Better psychological resilience and fewer physical symptoms and bother are associated with less demoralisation in PCSs.

Comparison between 68Ga-PSMA-11 PET/CT and multiparametric magnetic resonance imaging in patients with biochemically recurrent prostate cancer following robot-assisted radical prostatectomy.

BACKGROUND/PURPOSE: We sought to compare the diagnostic performances of 68Ga-PSMA-11 PET/CT and prostate/whole-abdomen multiparametric magnetic resonance imaging (PWAmpMRI) in Taiwanese patients with biochemically recurrent prostate cancer following robot-assisted radical prostatectomy. METHODS: Between June 2017 and December 2018, we prospectively enrolled 34 patients. Upon review of all available clinical and imaging data, a best valuable comparator (BVC) was defined on an individual basis in the light of a consensus reached by a multidisciplinary tumor board. Diagnostic positivity was investigated in relation to the different lesion types. RESULTS: On a patient-based analysis, 68Ga-PSMA-11 PET/CT and PWAmpMRI showed a moderate agreement (kappa coefficient = 0.62). 68Ga-PSMA-11 PET/CT identified local recurrences, regional, and non-regional lymph node metastases, and bone metastases in 15, 10, 1, and 5 patients, respectively. Conversely, PWAmpMRI detected these lesions in 26, 8, 1, and 4 patients, respectively. When the BVC was used as reference standard, the positive diagnostic rates for local recurrences, regional lymph node metastases, non-regional lymph node metastases, and bone metastases were 57.7%, 90.9%, 100%, and 100%, respectively for 68Ga-PSMA-11 PET/CT, and 100%, 72.7%, 100%, and 80% for PWAmpMRI, respectively. The use of both PWAmpMRI and 68Ga-PSMA-11 PET/CT showed a complete diagnostic yield for detecting both local recurrence and systemic failure when PSA levels reached 0.5 ng/mL. CONCLUSION: Due to urine radioactivity, 68Ga-PSMA-11 PET/CT performs less than PWAmpMRI on local recurrences. However, it can have a complementary diagnostic role in the detection of lymph node metastases and in identifying non-axial bone metastases beyond the PWAmpMRI scanning field.

Renal cell carcinoma and pathologic nodal disease: Implications for American Joint Committee on Cancer staging.

BACKGROUND: Lymph node (LN) metastases are associated with poor outcomes for patients with renal cell carcinoma (RCC). This study compared the survival outcomes of patients with stage III, node-positive disease (pT123 N1 M0 ) and patients with stage III, node-negative disease (pT3 N0 M0 ). METHODS: A database of 4652 patients with RCC of any histological subtype treated with surgery at The University of Texas MD Anderson Cancer Center from 1993 to 2012 was retrospectively assessed. A total of 115 patients with pT123 N1 M0 disease, 274 patients with pT3 N0 M0 disease, and 523 patients with pT123 N0/x M1 disease were included. Overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between each cohort. RESULTS: Median OS and CSS times were significantly better for pT3 N0 M0 patients than pT123 N1 M0 patients (OS, 10.2 vs 2.4 years, P < .0001; CSS, not reached vs 2.8 years, P < .0001). Similar median OS and CSS times were noted for pT123 N1 M0 and pT123 N0/x M1 patients (OS, 2.4 vs 2.4 years; P = .62; CSS, 2.8 vs 2.4 years; P = .10). In a multivariate analysis, tumor grade (hazard ratio [HR] for OS, 2.47; P < .0001; HR for CSS, 2.99; P < .0001) and pathologic LN involvement (HR for OS, 2.44; P < .0001; HR for CSS, 2.85; P < .0001) were associated with worse OS and CSS. CONCLUSIONS: Among RCC patients classified with stage III disease, those with pT123 N1 M0 disease had significantly worse survival than those with pT3 N0 M0 disease. OS and CSS were similar for patients with pT123 N1 M0 disease and patients with pT123 N0/x M1 disease (stage IV). If validated, these findings suggest that RCC patients with nodal disease should be reclassified as having stage IV disease.

Oncologic outcomes of patients with positive surgical margin after partial nephrectomy: a 25-year single institution experience.

PURPOSE: To evaluate oncologic outcomes and management of patients with microscopic positive surgical margin (PSM) after partial nephrectomy (PN) for renal cell carcinoma (RCC). METHODS: We reviewed our database to identify patients who underwent PN between 1990 and 2015 for RCC and had PSM on final pathology. A 1:3 matching was performed to a negative surgical margin (NSM) cohort. Kaplan-Meier method and log-rank test were used to estimate survival and differences in outcomes, respectively. Cox proportional hazards models were conducted to estimate the Hazards ratio. RESULTS: A total of 2297 patients underwent PN at our institution, of which 1863 (81%) had RCC. Microscopic PSM was found in 34 (1.8%) RCC patients who were matched to 100 patients with NSM. Of these 34 patients, local recurrence (n = 4), distant kidney recurrences (n = 4), and metastases (n = 5) developed during a median follow-up of 62 months. Bilateral tumors/tumors in a solitary kidney (n = 12/13, 92%), and multifocal tumors (n = 7/13, 54%) were found in patients who developed recurrence/metastasis. PSM patients were at a higher risk of shorter overall survival (p = 0.001), local recurrence-free survival (p = 0.003), distant recurrence-free survival (p = 0.032) and metastasis-free survival (p = 0.018). There was statistically significant association between PSM and bilateral tumors, prior treated RCC at presentation and higher nephrometry score in multivariable model. CONCLUSIONS: There was a low rate of microscopic PSM in our large cohort of patients undergoing PN despite tumor complexity. Higher nephrometry score, bilateral tumors, and prior treated RCC independently predicted PSM which showed worse survival, recurrence and metastasis compared to patients with NSM.

Outcomes of Patients with Renal Cell Carcinoma and Sarcomatoid Dedifferentiation Treated with Nephrectomy and Systemic Therapies: Comparison between the Cytokine and Targeted Therapy Eras.

PURPOSE: We studied overall survival and prognostic factors in patients with sarcomatoid renal cell carcinoma treated with nephrectomy and systemic therapy in the cytokine and targeted therapy eras. MATERIALS AND METHODS: This is a retrospective study of patients with sarcomatoid renal cell carcinoma who underwent nephrectomy and received systemic therapy at our center in the cytokine era (1987 to 2005) or the targeted therapy era (2006 to 2015). Multivariate regression models were used to determine the association of covariables with survival. RESULTS: Of the 199 patients with sarcomatoid renal cell carcinoma 167 (83.9%) died (median overall survival 16.5 months, 95% CI 15.2-20.9). Survival of patients with clear cell histology was significantly longer vs those with nonclear cell histology (p = 0.034). Patients with synchronous metastatic disease had significantly shorter survival than patients with metachronous metastatic disease (median 12.1 vs 23.3 months, p = 0.0064). Biopsy of the primary tumor or a metastatic site could detect the presence of sarcomatoid features in only 7.5% of cases. Although a significant improvement in survival rate was observed in the first year in patients treated in the targeted therapy era (p = 0.011), this effect was attenuated at year 2, disappeared at years 3 to 5 after diagnosis and was not evident in patients with poor risk features. CONCLUSIONS: Patients with sarcomatoid renal cell carcinoma still have poor prognosis with no clear long-term benefit of targeted therapy. This underscores the need to develop more effective systemic therapies for these patients.

Assessment of the psychometric properties of the traditional Chinese version of the cancer survivors' self-efficacy scale.

BACKGROUND: The reliability and validity of the traditional Chinese version of the Cancer Survivors' Self-Efficacy Scale (CS-SES-TC) has not been assessed. OBJECTIVE: To assess the psychometric properties of the Traditional Chinese version of the CS-SES-TC. METHODS: Participants were recruited from the outpatient departments of a hospital in Taiwan. A single questionnaire was administered to 300 genitourinary cancer survivors. The scales included in the initial questionnaire were the CS-SES-TC, the General Self-Efficacy Scale, the Center for Epidemiologic Studies Depression Scale (CES-D), and the Functional Assessment of Cancer Therapy-General scale (FACT-G). Data obtained from 300 survivors were used to confirm the structure through confirmatory factor analysis (CFA). RESULTS: The CFA results indicate that the 11-item CS-SES-TC is consistent with the original scale. Furthermore, it was identified as a unidimensional scale, with the model showing acceptable goodness-of-fit (CFI = 0.99, TLI = 0.97). The factor loading of each item in the CS-SES-TC was above 0.6 and had convergent validity. Based on multiple-group CFA testing, the change (ΔCFI) between the unconstrained and constrained models was ≤ 0.01, indicating that measurement invariance holds for gender. The participants' CS-SES-TC scores were positively correlated with their FACT-G scores and negatively correlated with their CES-D scores. The scales exhibited concurrent validity and discriminant validity. The CS-SES-TC had a Cronbach's α in the range of .97-.98. CONCLUSION: The CS-SES-TC had acceptable reliability and validity. Healthcare workers can use this scale for ongoing assessment of the cancer-related self-efficacy of cancer survivors.

Body image in patients with prostate cancer undergoing treatment with hormone therapy: Observational study using both a cross-sectional and longitudinal design.

This study aims to examine changes in body image (BI) over time and factors related to BI among patients with prostate cancer who receive hormone therapy (HT). A cross-sectional design and longitudinal design were utilized. Patients with prostate cancer who received HT were recruited from the urology outpatient departments in two hospitals in Taiwan between August 2017 and December 2020. Cross-sectional data were collected from 177 patients who had started HT for prostate cancer. Longitudinal data were collected from 34 newly diagnosed patients before receiving HT and at 1, 3, 6, and 12 months after HT. The variables measured included hormonal symptoms and distress, self-efficacy, and BI. The results showed that BI dissatisfaction ranged from 6.1% to 17.2%. Hormonal symptoms and distress (e.g. lack of vitality) were correlated with BI dissatisfaction. Education on the side effects of HT and coping strategies can be provided to patients to prevent BI dissatisfaction.

Integration of the cancer cell secretome and transcriptome reveals potential noninvasive diagnostic markers for bladder cancer.

PURPOSE: Bladder cancer (BLCA) is a major cancer of the genitourinary system. Although cystoscopy is the standard protocol for diagnosing BLCA clinically, this procedure is invasive and expensive. Several urine-based markers for BLCA have been identified and investigated, but none has shown sufficient sensitivity and specificity. These observations underscore the importance of discovering novel BLCA biomarkers and developing a noninvasive method for detection of BLCA. Exploring the cancer secretome is a good starting point for the development of noninvasive biomarkers for cancer diagnosis. EXPERIMENTAL DESIGN: In this study, we established a comprehensive secretome dataset of five representative BLCA cell lines, BFTC905, TSGH8301, 5637, MGH-U1, and MGH-U4, by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Expression of BLCA-specific secreted proteins at the transcription level was evaluated using the Oncomine cancer microarray database. RESULTS: The expressions of four candidates-COMT, EWSR1, FUSIP1, and TNPO2-were further validated in clinical human specimens. Immunohistochemical analyses confirmed that transportin-2 was highly expressed in tumor cells relative to adjacent noncancerous cells in clinical tissue specimens from BLCA patients, and was significantly elevated in BLCA urine compared with that in urine samples from aged-matched hernia patients (controls). CONCLUSIONS: Collectively, our findings suggest TNPO2 as a potential noninvasive tumor-stage or grade discriminator for BLCA management.

Lesion size may affect diagnostic capabilities of MRI-guided ultrasound fusion biopsy and cognitive targeted biopsy for clinically significant prostate cancer.

MRI-guided targeted biopsy (MRGB) was recommended as part of biopsy paradigm of prostate cancers by current guidelines. This study aimed to analyze the diagnostic efficacy of MRGB and systemic biopsy (SB), and to compare diagnostic capabilities within subgroups of MRGB: MRI-cognitive biopsy (MRCB) and MRI-fusion biopsy (MRFB). We retrospectively enrolled patients who underwent MRGB for suspicious malignant lesion(s) identified on MRI in a single tertiary center, sample size was 74 patients. An mpMRI was performed prior to biopsy and reviewed by an experienced radiologist specialized in prostate cancer. Per-person results of MRGB and each concomitant SB were analyzed as independent biopsies for its positive biopsy rate and positive core percentage. Per-lesion results of MRFB and MRCB were compared for the detection rate. Variables of interest were analyzed with t-test, chi-squared test, and logistic regression analysis. Statistical analyses were performed with IBM Statistical Product and Service Solutions (SPSS), Version 23 (IBM, Armonk, New York). Total of 74 patients fulfilled the inclusion criteria and were enrolled. MRFB had higher PCa detection rate comparing to both MRCB and SB (56.1%, 30.3%, and 33.9% respectively, p value = 0.036); clinically significant prostate cancer (csPCa) detection rate was also significantly higher in MRFB group (43.9%, 24.2%, and 16.9% in each group respectively, p value = 0.011). In per-lesion analysis, MRCB and MRFB had no significant difference in PCa and csPCa detection rate (41.0% vs. 26.2% and 29.5% vs. 16.7% respectively, p value = 0.090 and 0.103). In the lesion ≦ 1.3 cm group, MRFB could achieve higher PCa detection rate, comparing to MRCB (36.4% vs. 14.3%, p value = 0.047); there were also higher positive rates for PCa and csPCa per biopsied cores (22.1% vs. 6.8% and 15.6% vs. 2.7%, p value = 0.029 and 0.028, respectively). Further logistic regression of multi-variate analysis in subgroup of lesion ≦ 1.3 cm revealed that PIRADS score and biopsy method were significant predictors of positive biopsy result for PCa (p value = 0.045 and 0.026, respectively) and for csPCa (p value = 0.043 and 0.025, respectively). In patients receiving trans-perineal prostate biopsy, MRFB had higher cancer detection rate than MRCB and SB. In per lesion comparison, MRFB and MRCB had similar diagnostic accuracy. However, in lesions with diameter less than 1.3 cm, MRFB can provided better diagnose value for PCa and csPCa than MRCB.

Paraneoplastic leukocytosis induces NETosis and thrombosis in bladder cancer PDX model.

Paraneoplastic leukocytosis (PNL) in genitourinary cancer, though rare, can indicate aggressive behavior and poor outcomes. It has been potentially linked to cancer expressing G-CSF and GM-CSF, along with their respective receptors, exerting an autocrine/paracrine effect. In our study, we successfully established four patient-derived xenograft (PDX) lines and related cell lines from urothelial cancer (UC), conducting next-generation sequencing (NGS) for genetic studies. UC-PDX-LN1, originating from bladder cancer, exhibited two druggable targets - HRAS and ERCC2 - responding well to chemotherapy and targeted therapy, though not to tipifarnib, an HRAS inhibitor. Transcriptome analysis post-treatment illuminated potential mechanisms, with index protein analysis confirming their anticancer pathways. Mice implanted with UC-PDX-LN1 mirrored PNL observed in the patient's original tumor. Cytokine array and RT-PCR analyses revealed high levels of G-CSF and GM-CSF in our PDX and cell lines, along with their presence in culture media and tumor cysts.Leukocytosis within small vessels in and around the tumor, associated with NETosis and thrombus formation, suggested a mechanism wherein secreted growth factors were retained, further fueling tumor growth via autocrine/paracrine signaling. Disrupting this cancer cell-NETosis-thrombosis cycle, we demonstrated that anti-neutrophil or anticoagulant interventions enhanced chemotherapy's antitumor effects or prolonged survival in mice, even though these drugs lacked direct antitumor efficacy when used independently. Clinical observations in bladder cancer patients revealed PNL in 1.61% of cases (35/2162) with associated poor prognosis. These findings propose a novel approach, advocating for the combination of anticancer/NETosis/thrombosis strategies for managing UC patients presenting with PNL in clinical settings.

Periprostatic adipose tissue inhibits tumor progression by secreting apoptotic factors: A natural barrier induced by the immune response during the early stages of prostate cancer.

Prostate cancer (PCa) is the second most prevalent malignancy in men worldwide. The risk factors for PCa include obesity, age and family history. Increased visceral fat has been associated with high PCa risk, which has prompted previous researchers to investigate the influence of body composition and fat distribution on PCa prognosis. However, there is a lack of studies focusing on the mechanisms and interactions between periprostatic adipose tissue (PPAT) and PCa cells. The present study investigated the association between the composition of pelvic adipose tissue and PCa aggressiveness to understand the role played by this tissue in PCa progression. Moreover, PPAT-conditioned medium (CM) was prepared to assess the influence of the PPAT secretome on the pathophysiology of PCa. The present study included 50 patients with localized PCa who received robot-assisted radical prostatectomy. Medical records were collected, magnetic resonance imaging scans were analyzed and body compositions were calculated to identify the associations between adipose tissue volume and clinical PCa aggressiveness. In addition, CM was prepared from PPAT and perivesical adipose tissue (PVAT) collected from 25 patients during surgery, and its effects on the PCa cell lines C4-2 and LNCaP, and the prostate epithelial cell line PZ-HPV-7, were investigated using a cell proliferation assay and RNA sequencing (RNA-seq). The results revealed that the initial prostate-specific antigen level was significantly correlated with pelvic and periprostatic adipose tissue volumes. In addition, PPAT volume was significantly higher in patients with extracapsular tumor extension. PCa cell proliferation was significantly reduced when the cells were cultured in PPAT-CM compared with when they were cultured in control- and PVAT-CM. RNA-seq revealed that immune responses, and the cell death and apoptosis pathways were enriched in PPAT-CM-cultured cells indicating that the cytokines or other factors secreted from PPAT-CM induced PCa cell apoptosis. These findings revealed that the PPAT secretome may inhibit PCa cell proliferation by activating immune responses and promoting cancer cell apoptosis. This mechanism may act as a first-line defense during the early stages of PCa.

Association of regional anesthesia with oncological outcomes in patients receiving surgery for bladder cancer: A meta-analysis of observational studies.

Background: This meta-analysis was conducted to compare cancer recurrence and survival rates in patients with bladder cancer receiving surgery under general anesthesia alone (i.e., GA group) or regional anesthesia (RA) with or without GA (i.e., RA ± GA group). Methods: Literature search on Cochrane library, EMBASE, Google scholar, and Medline databases was performed to identify all relevant studies from inception to April 30, 2022. The primary outcome was cancer recurrence rate, while the secondary outcomes included overall survival rate and cancer-specific survival rate. Subgroup analyses were performed based on study design [(Propensity-score matching (PSM) vs. no-PSM)] and type of surgery [transurethral resection of bladder tumor (TURBT) vs. radical cystectomy]. Results: Ten retrospective studies with a total of 13,218 patients (RA ± GA group n=4,884, GA group n=8,334) were included. There was no difference between RA ± GA group and GA group in age, the proportion of males, severe comorbidities, the proportion of patients receiving chemotherapy, and the pathological findings (all p >0.05). Patients in the RA ± GA group had significantly lower rate of bladder cancer recurrence [odds ratio (OR): 0.74, 95%CI: 0.61 to 0.9, p=0.003, I2 = 24%, six studies] compared to those in the GA group. Subgroup analyses based on study design revealed a consistent finding, while the beneficial effect of RA ± GA on reducing cancer recurrence was only significant in patients receiving TURBT (p=0.02), but not in those undergoing radical cystectomy (p=0.16). There were no significant differences in overall survival rate and cancer-specific survival rate between RA ± GA and GA groups. Conclusions: For patients receiving surgery for bladder cancer, the application of regional anesthesia with or without general anesthesia is associated with significant decrease in cancer recurrence, especially in patients undergoing TURBT for non-muscle invasive bladder cancer. Because of the limited number of studies included and potential confounding factors, our results should be interpreted carefully. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022328134.

Can the Sandwich Method Be an Alternative Treatment Choice for BPH Patients With Large Prostates?

OBJECTIVE: To compare the efficacy and safety of the sandwich method with GreenLight photoselective vaporization (GLPVP) and bipolar transurethral resection (B-TURP) with those of the enucleation method in patients with BPH and a prostate volume ≥ 80 g. METHODS: Patients with BPH who underwent either the sandwich method with GLPVP and B-TURP or the enucleation method between 2014 and 2021 were included in the analysis. The primary outcome was the comparison of uroflowmetry results between the 2 groups. Safety analysis of the complication rates was also compared. RESULTS: The cohort included 55 patients in the sandwich group and 41 patients in the enucleation group. In the efficacy analysis, both groups showed comparable uroflowmetry results, except for a higher postoperative average flow rate in the enucleation group. Regarding perioperative parameters, the sandwich method required a longer operating time, and the enucleation group had a higher incidence of manual Foley irrigation. Both groups demonstrated similar postoperative complications. CONCLUSION: The sandwich method exhibited comparable efficacy and safety to the enucleation method in patients with BPH with a prostate volume ≥ 80 g. Thus, for surgeons who are familiar with GLPVP and B-TURP, the sandwich method may be an alternative surgical approach for BPH patients with large prostates.