Purine-Rich Element Binding Protein Alpha, a Nuclear Matrix Protein, Has a Role in Prostate Cancer Progression.

Solid tumors as well as leukemias and lymphomas show striking changes in nuclear structure including nuclear size and shape, the number and size of nucleoli, and chromatin texture. These alterations have been used in cancer diagnosis and might be related to the altered functional properties of cancer cells. The nuclear matrix (NM) represents the structural composition of the nucleus and consists of nuclear lamins and pore complexes, an internal ribonucleic protein network, and residual nucleoli. In the nuclear microenvironment, the NM is associated with multi-protein complexes, such as basal transcription factors, signaling proteins, histone-modifying factors, and chromatin remodeling machinery directly or indirectly through scaffolding proteins. Therefore, alterations in the composition of NM could result in altered DNA topology and changes in the interaction of various genes, which could then participate in a cascade of the cancer process. Using an androgen-sensitive prostate cancer cell line, LNCaP, and its androgen-independent derivative, LN96, conventional 2D-proteomic analysis of the NM proteins revealed that purine-rich element binding protein alpha (PURα) was detected in the NM proteins and differentially expressed between the cell lines. In this article, we will review the potential role of the molecule in prostate cancer.

An atlas of transcribed enhancers across helper T cell diversity for decoding human diseases.

Transcribed enhancer maps can reveal nuclear interactions underpinning each cell type and connect specific cell types to diseases. Using a 5' single-cell RNA sequencing approach, we defined transcription start sites of enhancer RNAs and other classes of coding and noncoding RNAs in human CD4+ T cells, revealing cellular heterogeneity and differentiation trajectories. Integration of these datasets with single-cell chromatin profiles showed that active enhancers with bidirectional RNA transcription are highly cell type-specific and that disease heritability is strongly enriched in these enhancers. The resulting cell type-resolved multimodal atlas of bidirectionally transcribed enhancers, which we linked with promoters using fine-scale chromatin contact maps, enabled us to systematically interpret genetic variants associated with a range of immune-mediated diseases.

Predictive Factors for Extracapsular Extension of Prostate Cancer to Select the Candidates for Nerve-sparing Radical Prostatectomy.

Nerve-sparing radical prostatectomy (NSRP) for prostate cancer (PC) enables better postoperative recovery of continence and potency but may increase the risk of positive surgical margins. This study aimed to investigate preoperative predictive factors for extracapsular extension (ECE) of PC to select patients for NSRP. We retrospectively evaluated 288 patients with PC (576 lobes) diagnosed with 12-core transrectal ultrasound-guided biopsy and magnetic resonance imaging (MRI) who underwent laparoscopic or robot-assisted radical prostatectomy at our institution. Surgical specimens and preoperative parameters (prostate-specific antigen, prostate volume, biopsy and MRI findings, preoperative therapy) were analyzed. Of 576 prostate lobes, the incidence Ipsilateral ECE was identified in 97 (16.8%) lobes. The higher number of unilateral positive biopsy cores, the highest Gleason score 8 or more and positive unilateral findings on MRI are significant higher in prostate sides with ECE in univariate analysis. In multivariate analysis, positive unilateral MRI findings (odds ratio [OR], 2.86; p < 0.001) and unilateral biopsy positive core ≥ 3 (OR, 3.73; p < 0.001) were independent predictors of unilateral ECE. The detection rate of unilateral ECE in those cases with two factors (side-specific positive biopsy core 2 or less and side-specific MRI findings negative) was 7.1% (19/269). Patients with fewer unilateral positive biopsy cores and negative unilateral MRI findings might be good candidates for NSRP.

Prognostic impact of histological discordance between transurethral resection and radical cystectomy.

OBJECTIVE: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. PATIENTS AND METHODS: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. RESULTS: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). CONCLUSION: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS.

Pre-operative Plasma Fibrinogen Level as a Potential Predictor of Pathological T3 Upstaging in Clinically Localized Renal Cell Carcinoma.

BACKGROUND/AIM: We investigated pre-operative factors for predicting pathological T3 (pT3) upstaging in clinical T1 renal cell carcinoma (RCC). PATIENTS AND METHODS: We evaluated 181 patients with renal tumors suspected to be clinical T1 RCC. All patients had undergone a partial or radical nephrectomy. Pre-operative parameters, including patient characteristics, RENAL nephrometry score and blood tests were analyzed to determine factors predicting pT3 upstaging. RESULTS: Eight (4.4%) tumors were diagnosed as pT3. Large tumor diameter, less than 4 mm distance between the tumor and the renal collecting system and a high level of preoperative plasma fibrinogen were associated with pT3 stage. Multivariate analysis showed that a preoperative plasma fibrinogen level >330 mg/dl was a significant independent factor predicting upstage (p=0.041). Furthermore, among patients diagnosed with RCC (n=162), a preoperative plasma fibrinogen level >330 mg/dl was related to poor overall survival (p<0.001) and poor recurrence-free survival (p=0.002). CONCLUSION: A high preoperative plasma fibrinogen level may be a predictor of pT3 upstaging and may suggest the need for radical nephrectomy rather than partial nephrectomy because of the associated poor oncological outcomes.

Pretreatment Lymphocyte to C-Reactive Protein Ratio: An Independent Predictor of Overall Survival in Metastatic Hormone-Naïve Prostate Cancer Patients.

INTRODUCTION: The purpose of this study was to investigate the clinical value of combination of systematic inflammatory factors in predicting the outcomes of primary androgen deprivation therapy (ADT) plus first-generation antiandrogen treatment in metastatic hormone-naïve prostate cancer (mHNPC) patients. MATERIALS AND METHODS: A total of 361 consecutive mHNPC patients from the discovery (n = 165) and validation (n = 196) cohorts were analyzed. All patients received primary ADT with surgical castration or pharmacologic castration accompanied by first-generation antiandrogens. We evaluated the prognostic impact of pretreatment lymphocyte to C-reactive protein ratio (LCR) on overall survival (OS) in both cohorts. RESULTS: The median follow-up in the discovery and validation cohorts was 43.4 and 50.9 months, respectively. In the discovery cohort, low LCR (using an optimal cutoff threshold of 14,025) was significantly correlated with poor OS compared with high LCR (P < .001). Multivariate analysis revealed that the biopsy Gleason score and LCR were independent prognostic factors for OS. In the validation cohort, low LCR was also significantly correlated with poor OS compared with high LCR (P = .001). A multivariate analysis revealed that the extent of disease on bone scan grade, lactate dehydrogenase, and LCR were all independent predictors of OS. CONCLUSIONS: Pretreatment low LCR is an independent predictor of poor OS in mHNPC patients. This may be informative in predicting the susceptible patients' developing worse outcomes after being treated with primary ADT plus first-generation antiandrogen.

Roles of the PARP Inhibitor in BRCA1 and BRCA2 Pathogenic Mutated Metastatic Prostate Cancer: Direct Functions and Modification of the Tumor Microenvironment.

Cancer cells frequently exhibit defects in DNA damage repair (DDR), leading to genomic instability. Mutations in DDR genes or epigenetic alterations leading to the downregulation of DDR genes can result in increased dependency on other DDR pathways. Therefore, DDR pathways could be a treatment target for various cancers. In fact, polyadenosine diphosphatase ribose polymerase (PARP) inhibitors, such as olaparib (Lynparza®), have shown remarkable therapeutic efficacy against BRCA1/2-mutant cancers through synthetic lethality. Recent genomic analytical advancements have revealed that BRCA1/BRCA2 pathogenic variants are the most frequent mutations among DDR genes in prostate cancer. Currently, the PROfound randomized controlled trial is investigating the efficacy of a PARP inhibitor, olaparib (Lynparza®), in patients with metastatic castration-resistant prostate cancer (mCRPC). The efficacy of the drug is promising, especially in patients with BRCA1/BRCA2 pathogenic variants, even if they are in the advanced stage of the disease. However, olaparib (Lynparza®) is not effective in all BRCA1/2 mutant prostate cancer patients and inactivation of DDR genes elicits genomic instability, leading to alterations in multiple genes, which eventually leads to drug resistance. In this review, we summarize PARP inhibitors' basic and clinical mechanisms of action against prostate cancer cells and discuss their effects on the tumor microenvironment.

Simple and reliable predictive factor for early recovery of urinary continence after non-nerve-sparing robot-assisted laparoscopic radical prostatectomy.

Post-prostatectomy urinary incontinence is one of the greatest concerns for both patients and urologists. The aim of this study is to elucidate simple and reliable factors contributing to early recovery of urinary continence (UC) and to develop a prediction model for early continence recovery after robot-assisted laparoscopic non-nerve-sparing radical prostatectomy (non-NS RARP). A retrospective analysis of 212 consecutive patients who underwent non-NS RARP by a single surgeon was carried out. Early recovery of urinary continence was defined as using no pads or one security pad per day within 1 month. Preoperative membranous urethral length (MUL) was measured on MRI, and the urinary continence at the standing position (UCSP) after removal of the catheter was examined during cystourethrography 6 days after surgery. Multivariable analysis was performed to detect predictive and postoperative factors associated with early recovery of urinary continence. The early continence recovery rate was 56.1%. Multivariable analysis revealed that MUL ≥ 13 mm, UCSP, and age ≤ 67 were the independent factors for early continence recovery. Early recovery rates were 97.1% for good risk, 76.3% for intermediate risk, and 28.4% for poor risk when divided into three risk groups by the sum score of three independent factors. Preoperative MUL, UCSP, and age are independent predictors of early recovery of UC in non-NS RARP, and our simple prediction model with the combination of the three factors could be a useful tool in clinical practice.

Dramatic response to pembrolizumab after pseudoprogression in a patient with advanced metastatic castration-resistant prostate cancer.

Introduction: Prostate cancer with a microsatellite instability-high or mismatch repair-deficient status is not common. Few reports of the response to pembrolizumab in metastatic castration-resistant prostate cancer in a real-world setting have been reported. This case report describes a dramatic response to pembrolizumab after initial pseudoprogression in a patient with microsatellite instability-high metastatic castration-resistant prostate cancer. Case presentation: A 70-year-old man was administered pembrolizumab for metastatic castration-resistant prostate cancer after the genetic evaluation of lymphadenectomy revealed a microsatellite instability-high status. His general condition dramatically improved after pseudoprogression. His favorable condition has been maintained for 1 year since the final dose. Conclusion: We experienced a case of dramatic response to pembrolizumab after pseudoprogression in a patient with advanced metastatic castration-resistant prostate cancer. In patients with metastatic castration-resistant prostate cancer and the microsatellite instability-high/mismatch repair-deficient phenotype, a few months follow-up is necessary to evaluate the efficacy of pembrolizumab.

Neonatal adrenal hemorrhage presenting as an acute scrotum: A case report on the rare presentation of right adrenal hemorrhage and contralateral left scrotal hematoma.

Introduction: Acute swelling and discoloration of the scrotum in a newborn is a rare condition and can have several causes such as testicular torsion, trauma, inguinal hernia, hydrocele, or adrenal hemorrhage. Case presentation: We report a neonate of adrenal hemorrhage presenting clinically as the acute scrotum. Definitive diagnosis was defined by ultrasonography and computed tomography scan, and the conservative management was successfully performed. Conclusion: Adrenal hemorrhage should be considered as one of the causes of acute scrotum in newborns. The abdominal ultrasonography, as well as the scrotal ultrasonography, should be performed routinely to achieve a definitive diagnosis to avoid unnecessary invasive procedures.

Pre-operative Serum Albumin as a Potential Predictor of Benign Lesions in Renal Masses.

BACKGROUND/AIM: We investigated pre-operative factors for predicting whether renal masses are benign in order to facilitate the selection of optimal candidates for pre-operative biopsy. PATIENTS AND METHODS: We evaluated 278 patients with renal masses suspected to be clinically T1 or T2 renal cell carcinoma. All patients had undergone a partial or radical nephrectomy. Pre-operative parameters, including patient characteristics, tumor size, and blood tests, were utilized to predict which lesions were benign. RESULTS: Twenty-five lesions (9.0%) were benign. Multivariate analysis showed that female sex [odds ratio (OR)=2.92, p=0.016], serum albumin ≥4.3 g/dl (OR=3.50, p=0.013), and tumor size <23 mm (OR=3.96, p=0.002) were significant independent factors for benign renal masses. The incidence of benign lesions in cases with all three factors (female sex, higher serum albumin, and smaller tumor size) was 4 of 16 (25.0%), which was significantly higher (p=0.037) than that in all cases (25/278; 9.0%). CONCLUSION: Relatively high pre-operative serum albumin levels may be a predictor of benign lesions when associated with female sex and smaller tumor size.

Usefulness of Biparametric Magnetic Resonance Imaging Combined With Prostate Specific Antigen Density in Pre-biopsy Detection of Clinically Insignificant Prostate Cancer.

BACKGROUND/AIM: The aim of this study was to identify simple and reliable factors to detect clinically insignificant prostate cancer (PC) for avoiding immediate prostate biopsies using biparametric magnetic resonance imaging (MRI), which consists of T2-weighted and diffusion-weighted imaging. PATIENTS AND METHODS: We retrospectively evaluated 427 men with suspected PC, who underwent biparametric MRI and standard 12-core transrectal prostate biopsy. MRI and prostate specific antigen density (PSAD) were analysed. To evaluate the combination of the two parameters, patients were divided into three groups (Group A: MRI negative and PSAD <0.23, Group B: MRI positive or PSAD ≥0.23, Group C: MRI positive and PSAD ≥0.23). A grade of ≥2 was defined as clinically significant PC. RESULTS: Clinically significant PC was detected in 46.5% of men with positive MRI findings, and 60.0% of men with PSAD ≥0.23. When combining MRI and PSAD, detection rates of clinically significant PC were 10.0%, 28.4% and 65.3% in group A, B and, C, respectively. CONCLUSION: Negative biparametric MRI findings with PSAD <0.23 might be a reliable evidence for avoiding immediate prostate biopsies.

Impact of noninvasive down-staging after transurethral resection of bladder tumor plus systemic chemotherapy on bladder-sparing strategy in patients with muscle-invasive bladder cancer.

OBJECTIVE: To identify the optimal selection criteria for bladder sparing strategy with transurethral resection of bladder tumor (TURBT) and systemic chemotherapy in patients with muscle-invasive bladder cancer (MIBC). METHODS: We conducted a retrospective cohort study in 71 patients with MIBC (T2-4aN0M0) who desire to bladder preservation received neoadjuvant chemotherapy (NAC) after maximal TURBT, followed by clinical restaging and second-TURBT. Fifty-eight of 71 patients with no residual tumor on the second-TURBT were placed on conservative management for bladder sparing (BS). Noninvasive down-staging (NID) was defined as cT0/Ta/Tis/T1N0 at first-TURBT after NAC and no residual tumor on second-TURBT. Overall survival (OS) and cystectomy-free survival (CFS) were assessed according to the response of NAC in the BS group by using Kaplan-Meier methods. Cox proportional hazards regression model was used to identify independent variables predicting OS. RESULTS: At a median follow-up of 40 months 5-year OS and CFS in patients with NID and non-NID were 89.1% versus 20.8% and 84.8% versus 16.7%, respectively. Multivariate analysis showed that the ≥3 cycles of NAC (hazard ratio [HR] 0.14, 95% confidential index [CI] 0.03-0.7; P = 0.017) and achievement of NID (HR 0.11, 95% CI 0.03-0.46, P = 0.002) favorably associated with OS. CONCLUSIONS: Patients who achieved NID might be optimal candidates for the bladder sparing strategy with maximum TURBT plus NAC followed by second-TURBT.

Successful management of a fistula between an external iliac artery and an ileal conduit with endovascular embolization and vascular bypass.

INTRODUCTION: Fistula formation between an ileac artery and an ileal conduit after radical cystectomy is a rare complication. CASE PRESENTATION: A 72-year-old woman underwent laparoscopic radical cystectomy with ileal conduit. After surgery, leakage of ileal-ureteral anastomosis with infection was observed. Five months after surgery, sudden bleeding from the ileal conduit occurred that stopped spontaneously. Contrast-enhanced computed tomography suggested a pseudo aneurysm of the right external iliac artery in contact with the ileal conduit. A fistula between the artery and ileal conduit was suspected. She underwent embolization of the common iliac artery and femorofemoral bypass. She had a good clinical course and no sign of hematuria over 6 months of follow-up. CONCLUSION: An episode of warning hemorrhage from the urostomy is an important sign of fistula, and endovascular treatment is a feasible approach to treat this condition.

Successfully Treated Lung and Renal Metastases from Primary Chondrosarcoma of the Scapula with Radiofrequency Ablation and Surgical Resection.

Since chondrosarcoma is a relatively rare type of malignant bone tumors characterized by its ability to produce a cartilage matrix and aggressive behavior, a consensus clinical management strategy has not been established. We report a 55-year-old woman who presented with renal metastasis arising from chondrosarcoma of the scapula. Chondrosarcoma of the left scapula was diagnosed 15 years earlier. After surgical resection of a local recurrence in the left scapula, she received focal radiofrequency ablation (RFA). She underwent focal RFA and surgical resection for a total of 21 times for lung metastases. Because invasion of the renal pelvis was suspected from urine cytology, she underwent laparoscopic nephroureterectomy. The histopathological findings showed metastatic chondrosarcoma involving the right renal parenchyma. The patient has remained clinically stable without recurrence for 18 months. To the best of our knowledge, this is the first report of metastatic chondrosarcoma of the lung and renal parenchyma with involvement of the renal pelvis in which remission was achieved with multimodal treatment including RFA and surgical resection.

[LEIOMYOSARCOMA ARISING FROM THE RENAL VEIN].

A 47-year-old female presented to a clinic complaining of right back pain. A CT scan revealed a right retroperitoneal mass and she was referred to our department for further evaluation. Contrast-enhanced CT and MRI revealed a right retroperitoneal mass (6 cm) in the hilum of the right kidney that invaded the right renal vein and inferior vena cava (IVC). Suspecting a tumor arising from retroperitoneal tissues involving the right renal vein and IVC, the decision was made to excise the tumor with the right kidney, renal vein, and a portion of the IVC. The histologic findings indicated that the tumor was a leiomyosarcoma originating from the renal vein wall. The tumor cells were spindle-shaped and stained positive for desmin, caldesmon and HHF35. The post-operative course was uneventful and she was recurrence-free 20 months after surgery. In addition to presenting a case of a leiomyosarcoma of the renal vein, a short review of the literature is provided.

A Combination of Findings Obtained from Pre- and Postoperative Imaging Predict Recovery of Urinary Continence After Non-nerve-sparing Laparoscopic Radical Prostatectomy.

BACKGROUND/AIM: The aim of the study was to identify the reliable predictor for early recovery of urinary continence (UC) after non-nerve-sparing laparoscopic radical prostatectomy (NNS-LRP) according to the findings of pre- and postoperative imaging. MATERIALS AND METHODS: A retrospective analysis of 215 patients who underwent NNS-LRP was carried out. Early recovery of UC was defined as using no pads or one security pad per day within 3 months. Preoperative membranous urethral length (MUL) measured on MRI and postoperative bladder neck angle (BNA) identified by cystography were analyzed to evaluate the relationship with recovery of UC. Patients were divided into three groups based on MUL and BNA (Group A: MUL ≥12.1 mm and BNA ≥103°, Group B: either MUL ≥12.1 mm or BNA ≥103°, Group C: MUL <12.1 mm and BNA <103°. RESULTS: Early recovery rates were 80.3% in patients with MUL ≥12.1 mm, 37.5% in patients with MLU<12.1 (p<0.001), and 77.8% in patients with BNA ≥103°, 50% in patients with BNA <103°(p<0.001). In the combination of the two parameters, early recovery rates were 90.4%, 58%, and 36.1% in group A, B and C respectively (p<0.001). Kaplan-Meier curve of the time to recovery of UC showed significant differences among the three groups (log rank test: p<0.001). CONCLUSION: A combination of preoperative MUL and postoperative BNA was the reliable predictor of recovery of UC after NNS-LRP. Longer MUL with wider BNA is significantly and positively associated with an early recovery of UC.

The role of continuous saline bladder irrigation after transurethral resection in patients with high-grade non-muscle-invasive bladder cancer.

OBJECTIVE: To compare the efficacy and safety of continuous saline bladder irrigation (CSBI) to a single immediate instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) in patients with high grade primary non-muscle invasive bladder cancer (HG-NMIBC). MATERIALS AND METHODS: This study retrospectively reviewed 250 patients with primary NMIBC who were enrolled in a prospective randomized trial of CSBI vs single instillation of mitomycin C (SI-MMC) immediately after TURBT. Results of histopathology were re-reviewed using the World Health Organization (WHO) 2004/2016 classification. Of the 250 patients, 151 HG-NMIBC patients (78 in the CSBI group and 73 in the SI-MMC group) were evaluated according to the recurrence and progression rates and adverse events. RESULTS: The median follow-up period was 58 months. No significant differences for patients' characteristics were observed between the CSBI group and SI-MMC group. There was no statistically significant difference between the CSBI group and SI-MMC. group regarding recurrence rates of 12, 18 and 24 months (25.6% vs 23.3%、28.5% vs 23.3% and 32.1% vs 28.8%, respectively), time to first recurrence (12.6 ± 11 vs 12.4 ± 10.1 months) and progression rate (8.9% vs 8.2%). The incidence of adverse events was significantly lower in the C.S.B.I. group. CONCLUSION: The difference of recurrence and progression rate between CSBI and SI-MMC after TURBT was not statistically significant in HG-NMIBC, although a larger study is necessary to prove its equivalence or non-inferiority. CSBI after TURBT is easy to administer with a reduced risk of adverse events, and may be a treatment choice for patients with HG-NMIBC.