Combination of [18F]FDG and [18F]PSMA-1007 PET/CT predicts tumour aggressiveness at staging and biochemical failure postoperatively in patients with prostate cancer.

PURPOSE: [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has limitations in prostate cancer (PCa) detection owing to low glycolysis in the primary tumour. Recently, prostate-specific membrane antigen (PSMA) PET/CT has been useful for biochemical failure detection and radioligand therapy (RLT) guidance. However, few studies have evaluated its use in primary prostate tumours using PSMA and [18F]FDG PET/CT. This study aimed to evaluate [18F]PSMA-1007 and [18F]FDG PET/CT for primary tumour detection and understand the association of metabolic heterogeneity with clinicopathological characteristics at staging and postoperatively. METHOD: This prospective study included 42 index tumours (27 acinar and 15 ductal-dominant) in 42 patients who underwent [18F]PSMA-1007 and [18F]FDG PET/CT and subsequent radical prostatectomy. All patients were followed for a median of 26 mo, and serum prostate-specific antigen levels were measured every 3 mo to evaluate biochemical failure. One-way analysis of variance, Tukey's multiple comparison test, and Fisher's exact test were performed. RESULTS: All 42 index tumours were detected on [18F]PSMA-1007 PET/CT, whereas only 15 were detected on [18F]FDG PET/CT (62.3% vs. 37.7%, p < 0.0001). A high SUVmax for [18F]PSMA-1007 was observed in tumours with high Gleason scores (GS 6-7 vs. GS 8-10; 12.1 vs. 20.1, p < 0.05). Tumours with [18F]FDG uptake were mostly ductal dominant (acinar-dominant 4/27; ductal-dominant; 11/15, p < 0.001), with lower [18F]PSMA-1007 uptake than tumours without [18F]FDG uptake (SUVmax 16.58 vs. 11.19, p < 0.001). There were 16.6% (7/42) of patients with pStage IV in whom the primary tumours were [18F]FDG positive. Biochemical failure was observed in 14.8% (4/27) of patients with [18F]FDG negative tumours but in 53.3% (8/15) of patients with [18F]FDG positive tumours (p = 0.013). CONCLUSIONS: [18F]PSMA-1007 PET/CT was superior to [18F]FDG PET/CT in detecting primary PCa. In contrast, tumours with [18F]FDG uptake are associated with larger size, a ductal-dominant type, and likely to undergo metastasis at staging and biochemical failure postoperatively.

Effects of exercise during active surveillance for prostate cancer: A systematic review and meta-analysis.

PURPOSE: The efficacy of exercise in men with prostate cancer (PCa) on active surveillance (AS) remains unclear. In this meta-analysis, we aimed to examine the effects of exercise in PCa patients on AS. METHODS: A literature search was conducted in PubMed, EMBASE, and the Cochrane Library using search terms, including exercise, PCa, AS, and randomized controlled trials (RCTs). The means and standard deviations for peak oxygen consumption (VO2peak), prostate-specific antigen (PSA) levels, and quality of life (QoL) were extracted for the intervention and control groups. A random-effects model was used to summarize the effects of exercise. RESULTS: Of the 158 identified studies, six RCTs with 332 patients were included. The interventions included lifestyle modifications (aerobic exercise + diet) in three studies and different exercise modalities in three studies. The intervention duration was 2-12 months; three interventions were supervised and three were self-directed. The pooled weighted mean difference between exercise and usual care for VO2peak was 1.42 mL/kg/min (95% confidence interval [CI]: 0.30 to 2.54, P ≤ 0.001). A non-significant effect was observed for QoL (pooled standardized mean difference [SMD]: 0.24, 95% CI: - 0.03 to 0.51, P = 0.08) which became statistically significant and stronger after excluding one outlier study (P < 0.001). Exercise also had a positive effect on PSA levels (pooled SMD: - 0.43, 95% CI: - 0.87 to 0.01, P = 0.05). CONCLUSION: Exercise improves cardiorespiratory fitness and may improve QoL and PSA levels in men with PCa on AS. Further studies with larger sample sizes are warranted to obtain more reliable results.

Deciphering the Role of ERBB3 Isoforms in Renal Cell Carcinoma: A Comprehensive Genomic and Transcriptomic Analysis.

ERBB3, a key member of the receptor tyrosine kinase family, is implicated in the progression and development of various human cancers, affecting cellular proliferation and survival. This study investigated the expression of ERBB3 isoforms in renal clear cell carcinoma (RCC), utilizing data from 538 patients from The Cancer Genome Atlas (TCGA) Firehose Legacy dataset. Employing the SUPPA2 tool, the activity of 10 ERBB3 isoforms was examined, revealing distinct expression patterns in RCC. Isoforms uc001sjg.3 and uc001sjh.3 were found to have reduced activity in tumor tissues, while uc010sqb.2 and uc001sjl.3 demonstrated increased activity. These variations in isoform expression correlate with patient survival and tumor aggressiveness, indicating their complex role in RCC. The study, further, utilizes CIBERSORTx to analyze the association between ERBB3 isoforms and immune cell profiles in the tumor microenvironment. Concurrently, Gene Set Enrichment Analysis (GSEA) was applied, establishing a strong link between elevated levels of ERBB3 isoforms and critical oncogenic pathways, including DNA repair and androgen response. RT-PCR analysis targeting the exon 21-23 and exon 23 regions of ERBB3 confirmed its heightened expression in tumor tissues, underscoring the significance of alternative splicing and exon utilization in cancer development. These findings elucidate the diverse impacts of ERBB3 isoforms on RCC, suggesting their potential as diagnostic markers and therapeutic targets. This study emphasizes the need for further exploration into the specific roles of these isoforms, which could inform more personalized and effective treatment modalities for renal clear cell carcinoma.

External validation of yonsei nomogram predicting chronic kidney disease development after partial nephrectomy: An international, multicenter study.

OBJECTIVE: To externally validate Yonsei nomogram. METHODS: From 2000 through 2018, 3526 consecutive patients underwent on-clamp PN for cT1 renal masses at 23 centers were included. All patients had two kidneys, preoperative eGFR ≥60 ml/min/1.73 m2, and a minimum follow-up of 12 months. New-onset CKD was defined as upgrading from CKD stage I or II into CKD stage ≥III. We obtained the CKD-free progression probabilities at 1, 3, 5, and 10 years for all patients by applying the nomogram found at https://eservices.ksmc.med.sa/ckd/. Thereafter, external validation of Yonsei nomogram for estimating new-onset CKD stage ≥III was assessed by calibration and discrimination analysis. RESULTS AND LIMITATION: Median values of patients' age, tumor size, eGFR and follow-up period were 47 years (IQR: 47-62), 3.3 cm (IQR: 2.5-4.2), 90.5 ml/min/1.73 m2 (IQR: 82.8-98), and 47 months (IQR: 27-65), respectively. A total of 683 patients (19.4%) developed new-onset CKD. The 5-year CKD-free progression rate was 77.9%. Yonsei nomogram demonstrated an AUC of 0.69, 0.72, 0.77, and 0.78 for the prediction of CKD stage ≥III at 1, 3, 5, and 10 years, respectively. The calibration plots at 1, 3, 5, and 10 years showed that the model was well calibrated with calibration slope values of 0.77, 0.83, 0.76, and 0.75, respectively. Retrospective database collection is a limitation of our study. CONCLUSIONS: The largest external validation of Yonsei nomogram showed good calibration properties. The nomogram can provide an accurate estimate of the individual risk of CKD-free progression on long-term follow-up.

Optical genome mapping identifies clinically relevant genomic rearrangements in prostate cancer biopsy sample.

BACKGROUND: Prostate cancer (PCa) is characterized by complex genomic rearrangements such as the ETS oncogene family fusions, yet the clinical relevance is not well established. While paneled genetic tests of DNA repair genes are recommended in advanced PCa, conventional genomic or cytogenetic tools are not ideal for genome-wide screening of structural variations (SVs) such as balanced translocation due to cost and/or resolution issues. METHODS: In this study, we tested the feasibility of whole-genome optical genomic mapping (OGM), a newly developed platform for genome-wide SV analysis to detect complex genomic rearrangements in consecutive unselected PCa samples from MRI/US-fusion targeted biopsy. RESULTS: We tested ten samples, and nine (90%) passed quality check. Average mapping rate and coverage depth were 58.1 ± 23.7% and 157.3 ± 97.7×, respectively (mean ± SD). OGM detected copy number alterations such as chr6q13 loss and chr8q12-24 gain. Two adjacent tumor samples were distinguished by inter/intra-chromosomal translocations, revealing that they're from the same ancestor. Furthermore, OGM detected large deletion of chr13q13.1 accompanied by inter-chromosomal translocation t(13;20)(q13.1;p13) occurring within BRCA2 gene, suggesting complete loss of function. CONCLUSION: In conclusion, clinically relevant genomic SVs were successfully detected in PCa samples by OGM. We suggest that OGM can complement panel sequencing of DNA repair genes BRCA1/2 or ATM in high-risk PCa.

Characteristics of BRCA2 Mutated Prostate Cancer at Presentation.

Genetic alterations of DNA repair genes, particularly BRCA2 in patients with prostate cancer, are associated with aggressive behavior of the disease. It has reached consensus that somatic and germline tests are necessary when treating advanced prostate cancer patients. Yet, it is unclear whether the mutations are associated with any presenting clinical features. We assessed the incidences and characteristics of BRCA2 mutated cancers by targeted sequencing in 126 sets of advanced prostate cancer tissue sequencing data. At the time of diagnosis, cT3/4, N1 and M1 stages were 107 (85%), 54 (43%) and 35 (28%) samples, respectively. BRCA2 alterations of clinical significance by AMP/ASCO/CAP criteria were found in 19 of 126 samples (15.1%). The BRCA2 mutated cancer did not differ in the distributions of TNM stage, Gleason grade group or histological subtype compared to BRCA2 wild-type cancers. Yet, they had higher tumor mutation burden, and higher frequency of ATM and BRCA1 mutations (44% vs. 10%, p = 0.002 and 21% vs. 4%, p = 0.018, respectively). Of the metastatic subgroup (M1, n = 34), mean PSA was significantly lower in BRCA2 mutated cancers than wild-type (p = 0.018). In the non-metastatic subgroup (M0, n = 64), PSA was not significantly different (p = 0.425). A similar trend was noted in multiple metastatic prostate cancer public datasets. We conclude that BRCA2 mutated metastatic prostate cancers may present in an advanced stage with relatively low PSA.

Clinical Outcomes After Urinary Diversion for Malignant Ureteral Obstruction Secondary to Non-urologic Cancer: An Analysis of 778 Cases.

BACKGROUND: This study investigated patient outcomes after urinary diversion in order to manage malignant ureteral obstruction caused by non-urologic cancers and to evaluate predictive factors for overall survival. METHODS: The study retrospectively reviewed patients with non-urologic malignancies who underwent ureteral stenting or percutaneous nephrostomy for ureteral obstruction between 2006 and 2014. The variables for predicting overall survival were identified by Cox regression analysis. RESULTS: The study enrolled 778 patients, including 522 patients who underwent ureteral stenting and 256 patients who underwent percutaneous nephrostomy. Renal function was assessed immediately and then 2 weeks after urinary diversion. The median survival period was 5 months (interquartile range [IQR] 2-12 months). A total of 708 patients died. The patients who received chemotherapy after urinary diversion had a survival gain of 7 months compared with the patients who did not receive subsequent chemotherapy (p < 0.001). The survival rate did not differ between the various types of urinary diversion (p = 0.451). In the multivariate analysis, lower survival rates were significantly associated with male sex; previous chemotherapy without radiotherapy; an increasing number of events related to malignant dissemination; low preoperative hemoglobin (< 10 mg/dL), albumin (< 3 g/dL), and estimated glomerular filtration (< 60 mL/min/1.73 m2) rates; and no subsequent chemotherapy or radiotherapy. CONCLUSIONS: In cases of ureteral obstruction caused by non-urologic malignancies, the overall survival was poor. However, the patients who received chemotherapy after urinary diversion had a survival gain of 7 months. Therefore, urinary diversion could be considered to preserve renal function for subsequent chemotherapy, whereas patients with the poor prognostic factors should be presented with the option of no intervention.

Retzius Sparing Robot-Assisted Radical Prostatectomy Conveys Early Regain of Continence over Conventional Robot-Assisted Radical Prostatectomy: A Propensity Score Matched Analysis of 1,863 Patients.

PURPOSE: We compared early continence recovery after surgical treatment of prostate cancer with Retzius sparing robot-assisted radical prostatectomy and conventional robot-assisted radical prostatectomy. MATERIALS AND METHODS: Robot-assisted radical prostatectomy was done by a single surgeon in 1,863 cases between October 2005 and May 2018 using the conventional and the Retzius sparing technique in 1,150 and 713, respectively. To compare continence outcomes between the groups propensity score matching was performed using 9 preoperative variables, including age, body mass index, prostate specific antigen, biopsy Gleason Grade Group, clinical T stage, prostate volume on transrectal ultrasound, and the I-PSS (International Prostate Symptom Score), I-PSS quality of life score and International Index of Erectile Function-5 scores. Continence was assessed by the pad count every month postoperatively until month 6 and was converted to a binary outcome. RESULTS: After propensity score matching 609 cases per group were matched with no significant difference in all 9 variables. The Kaplan-Meier curve analysis revealed that Retzius sparing robot-assisted radical prostatectomy was associated with a significantly better continence recovery rate than conventional robot-assisted radical prostatectomy during the 6-month study period (p <0.001). CONCLUSIONS: Based on propensity score matching with multiple variables and a large case series, Retzius sparing robot-assisted radical prostatectomy can be a candidate for future robot-assisted radical prostatectomy. It achieves better early continence recovery, a short operative time and early recovery compared to conventional robot-assisted radical prostatectomy.

Lessons learned from clinical outcome and tumor features of patients underwent selective artery embolization due to postoperative bleeding following 2076 partial nephrectomies: propensity scoring matched study.

PURPOSE: To evaluate the clinical and tumor characteristics in patients undergoing selective artery embolization (SAE) for bleeding after partial nephrectomy (PN). METHODS: We retrospectively evaluated patients who underwent SAE from 2076 patients who underwent PN. The clinical and tumor characteristics of these patients were analyzed using entire data and propensity score matching (PSM). 76 patients who underwent PN (control, n = 38 patients; SAE, n = 38) were enrolled in PSM. RESULTS: SAE was performed in 41 patients who underwent open (19/1171), laparoscopic (4/60), and robot-assisted PN (18/845). The median period from PN to SAE was 12 days (interquartile range 8-24 day). The most common symptom of 31 (75.61%) patients was gross hematuria, followed by flank pain (3/41). Follow-up imaging revealed large pseudoaneurysm in 7 asymptomatic patients. The main reason for SAE on angiography was pseudoaneurysm (32/41), followed by arteriovenous fistula (5/41). Technical and clinical success was achieved in all patients. There was no statistical difference in the estimated glomerular filtration rate after 1 year, surgical methods, or baseline characteristics between the two groups. Conversely, there was statistically significant difference in ischemic time in the entire data and PSM. In the embolization group, renal masses showed statistically significant endophytic (p = 0.006) and posterior (p = 0.028) characteristics. CONCLUSIONS: SAE is an effective method for controlling postoperative bleeding while preserving renal function after PN. And, we suggest more attentive postoperative surveillance about vascular complications in patients with longer ischemia time or renal masses with endophytic and posterior locations.

Comparison of Biochemical Recurrence After Robot-assisted Laparoscopic Radical Prostatectomy with Volatile and Total Intravenous Anesthesia.

Aims: Recurrence after cancer surgery is a major concern in patients with cancer. Growing evidence from preclinical studies has revealed that various anesthetics can influence the immune system in different ways. The current study compared the long-term biochemical recurrence of prostate cancer after robot-assisted laparoscopic radical prostatectomy (RALP) in terms of selection of anesthetic agent between total intravenous anesthesia (TIVA) with propofol/remifentanil and volatile anesthetics (VA) with sevoflurane or desflurane/remifentanil. Methods: We followed up oncologic outcomes of patients who underwent RALP from two previous prospective randomized controlled trials, and the outcomes of those who received TIVA (n = 64) were compared with those who received VA (n = 64). The follow-up period lasted from November 2010 to March 2019. Results: Both TIVA and VA groups showed identical biochemical recurrence-free survivals at all-time points after RALP. The following predictive factors of prostate cancer recurrence were determined by Cox regression: colloid input [hazard ratio (HR)=1.002, 95% confidence interval (CI): 1.000-1.003; P = 0.011], initial prostate-specific antigen level (HR=1.025, 95% CI: 1.007-1.044; P = 0.006), and pathological tumor stage 3b (HR=4.217, 95% CI:1.207-14.735; P = 0.024), but not the anesthetic agent. Conclusions: Our findings demonstrate that both TIVA with propofol/remifentanil and VA with sevoflurane or desflurane/remifentanil have comparable effects on oncologic outcomes in patients undergoing RALP.

Effect of different general anaesthetics on ventricular repolarisation in robot-assisted laparoscopic prostatectomy.

BACKGROUND: Ventricular repolarisation is affected differently by the types of anaesthetics used. This study aimed to compare the effect of different types of anaesthetics on ventricular repolarisation during robot-assisted laparoscopic radical prostatectomy (RALP). METHODS: Sixty-nine patients were randomly assigned in a 1:1:1 ratio to the Sevoflurane (sevoflurane/remifentanil), Desflurane (desflurane/remifentanil) or total intravenous anaesthesia (TIVA [propofol/remifentanil]) groups; however, only 67 patients completed the study. The primary outcome was heart rate-corrected QT (QTc) interval collected at nine time points during RALP. Bazett's (QTcB) and Fridericia's (QTcF) formulae were used for QT interval correction. The secondary outcomes were Tpeak-Tend (Tp-e) interval and Tp-e/QT ratio that were collected at the same time points. RESULTS: The QTcB and QTcF intervals were significantly prolonged during surgery in all groups; however, these values showed significant intergroup differences with time. After assuming the Trendelenburg position, the QTcB and QTcF intervals were significantly longer in the Desflurane group than in the other two groups, and this prolongation continued until the end of surgery. Intra-operatively, the QTcB and QTcF intervals exceeded 450 ms in six and five patients, respectively, in the Desflurane group, but in none in the TIVA group. Moreover, the incidence of intra-operative QTc interval prolongation >20 ms and >60 ms was significantly higher in the Desflurane group than in the TIVA group. There were no significant differences in Tp-e intervals and Tp-e/QT ratio among the three groups during surgery. CONCLUSIONS: To minimise QTc interval prolongation during RALP, TIVA with propofol/remifentanil is recommended for general anaesthesia.

The prognostic impact of downgrading and upgrading from biopsy to radical prostatectomy among men with Gleason score 7 prostate cancer.

BACKGROUND: Recently, a new prostate cancer (PC) grading system was introduced, where Gleason score (GS) 7 was divided into 3 + 4 = 7 and 4 + 3 = 7 due to the different prognoses associated with each tumor type. However, whether downgrading or upgrading from needle biopsy (NB) to radical prostatectomy (RP) affects oncologic outcomes is currently unknown. Herein, we investigated the prognostic impact of downgrading and upgrading from NB to RP among men with GS 7 PC. METHODS: We retrospectively reviewed the medical records of 3003 patients with localized PC who underwent RP between 2005 and 2014. We included 692 patients with GS 7 PC on both NB and RP specimens. We analyzed the data using Kaplan-Meier methods and Cox proportional hazard models. RESULTS: Of the 692 patients enrolled in this study, 389 (56.2%) and 303 (43.8%) patients had RP GS 3 + 4 = 7 and RP GS 4 + 3 = 7 PC, respectively. On the basis of NB and RP GS, 264 (38.1%), 125 (18.1%), 142 (20.5%), and 161 (23.3%) patients were classified as 3 + 4/3 + 4, 4 + 3/3 + 4, 3 + 4/4 + 3, and 4 + 3/4 + 3, respectively. Kaplan-Meier curves showed significant differences in biochemical recurrence (BCR)-free survival across the groups (P < .001). In the multivariate analyses, these groups were significantly associated with BCR (4 + 3/3 + 4: hazard ratio [HR], 1.675; 3 + 4/4 + 3: HR, 1.908; and 4 + 3/4 + 3: HR, 2.699). CONCLUSIONS: Downgrading and upgrading from NB to RP was an independent predictor of BCR in men with GS 7 PC, which could be due to the amount of Gleason pattern 4.

Probe-Based Confocal Laser Endomicroscopy During Transurethral Resection of Bladder Tumors Improves the Diagnostic Accuracy and Therapeutic Efficacy.

PURPOSE: This study was designed to assess the diagnostic accuracy and therapeutic efficacy of probe-based confocal laser endomicroscopy (pCLE), which provides real-time, in vivo histological information during transurethral resection of bladder tumors. METHODS: We performed a prospective study between August 2013 and August 2014. pCLE was performed on a total of 119 lesions in 75 patients. We analyzed the diagnostic accuracy of pCLE by comparing the confocal image reports with the pathology reports of surgical specimen. Confocal images were interpreted by a single urologist blinded to the pathology reports. The therapeutic efficacy was analyzed by comparing the outcomes in pCLE and non-pCLE groups. RESULTS: In a total of 119 lesions, 23 were benign and 96 were malignant. The detection accuracy for malignant lesions with pCLE was determined with a sensitivity and a positive predictive value (PPV) of 91.7% and 93.6%, respectively. For high-grade versus low-grade bladder cancer, sensitivity and PPV of pCLE were 94.5% and 89.7%, respectively. Distinguishing carcinoma in situ from inflammatory lesions also was accurate with sensitivity, specificity, and PPV of 71.4%, 81.3%, and 83.3%, respectively. The Kaplan-Meier curves revealed that the recurrence-free survival rate was significantly higher in the pCLE group than in the non-pCLE group (p = 0.031). CONCLUSIONS: Probe-based confocal laser endomicroscopy is a promising method to provide the surgeon during the transurethral resection of a bladder tumor with real-time tumor histology, regardless of the tumor's gross appearance. Furthermore, it also may improve the therapeutic efficacy with longer recurrence-free periods.

Differences in the Efficacies of Pazopanib and Gemcitabine/Docetaxel as Second-Line Treatments for Metastatic Soft Tissue Sarcoma.

BACKGROUND: We retrospectively investigated the treatment outcomes of second-line treatment with pazopanib or gemcitabine/docetaxel in patients with advanced soft tissue sarcoma (STS). METHODS: Ninety-one patients who were treated with pazopanib or gemcitabine/docetaxel for advanced STS between 1995 and 2015 were analyzed. RESULTS: Forty-six and 45 patients received pazopanib and gemcitabine/docetaxel, respectively. The median progression-free survival for the group treated with pazopanib was 4.5 months compared with 3.0 months for the gemcitabine/docetaxel group (p = 0.593). The median overall survival for the group treated with pazopanib was 12.6 months compared with 14.2 months for the gemcitabine/docetaxel group (p = 0.362). The overall response rates (ORRs) were 6.5 and 26.7% in the pazopanib and gemcitabine/docetaxel groups, respectively. The following parameters had ORRs favoring gemcitabine/docetaxel: age ≥50 years (31.6 vs. 2.9%, p = 0.006), histologic grade 1-2 (40.9 vs. 0%, p = 0.001), and poor first-line treatment response (23.3 vs. 3.0%, p = 0.022). Gemcitabine/docetaxel was associated with better ORRs for the following histologic subtypes: leiomyosarcoma (p = 0.624), malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma (p = 0.055), and angiosarcoma (p = 0.182). However, the ORR of synovial sarcoma favored pazopanib (p = 0.99). CONCLUSIONS: The efficacies of pazopanib and gemcitabine/docetaxel as second-line treatments after doxorubicin or ifosfamide failure differed among clinical and histologic subgroups and appeared to facilitate a more personalized treatment approach for advanced STS.

Effect of prostate gland weight on the surgical and oncological outcomes of extraperitoneal robot-assisted radical prostatectomy.

BACKGROUND: Robot-assisted radical prostatectomy (RARP) is performed by urologists as one of the surgical procedures for treating prostate cancer. Numerous studies have been published with regard to the impact of prostate weight on performing RARP but were limited by the insufficient number of patients and use of the transperitoneal approach. This study aimed to determine the effect of prostate gland weight on the surgical and short-term oncological outcomes of RARP using the extraperitoneal approach. METHODS: In total, 1168 patients who underwent extraperitoneal RARP (EP-RARP) performed by a single surgeon at Yonsei University Severance Hospital between May 2009 and May 2016 were included in the study. The patients were divided into 4 groups according to the prostate weight measured by transrectal ultrasonography preoperatively. Intraoperative and postoperative outcomes were analyzed retrospectively. One-way analysis of variance and the chi-square test were used in the statistical analyses. RESULTS: Age, the Gleason score, clinical stage, and pathological stage were significantly different. Patients with a larger prostate size had a longer console time and higher estimated blood loss (P < 0.05). There were no significant differences between the 4 groups in length of hospital stay, duration of catheterization, blood transfusion, body mass index, prostate-specific antigen (PSA) level, history of abdominal surgery, intraoperative complications, positive surgical margin, incidence of lymphocele, and PSA recurrence after 1 year. CONCLUSIONS: The console time and estimated blood loss were significantly increased with a larger prostate size. However, there were no significant differences in the oncologic outcome and intraoperative complications, suggesting that EP-RARP requires meticulous bleeding control in patients with a prostate weighing > 75 g, and if appropriate management is implemented for blood loss intraoperatively, EP-RARP can be performed regardless of the prostate size.

Clinical significance and predictors of oncologic outcome after radical prostatectomy for invisible prostate cancer on multiparametric MRI.

BACKGROUND: The objective of our study was to evaluate the clinical significance of invisible prostate cancer (iPCa) on multiparametric magnetic resonance imaging (mpMRI) by analyzing clinical parameters and oncologic outcomes. METHODS: We retrospectively reviewed the records of patients treated with radical prostatectomy (RP) from 2010 to 2015 at our institution. Before RP, all patients were confirmed to have prostate cancer based on prostate biopsy. We excluded patients who underwent neoadjuvant therapy. Additionally, we excluded patients who had incomplete mpMRI based on PI-RADS (Prostate Imaging Reporting and Data System). iPCa was defined as having no grade 3 or higher region of interests using a scoring system established by PI-RADS without limitations on interpretation from mpMRI by radiologists. We selected patients with iPCa using this protocol. We analyzed data using univariate and multivariate cox regression analysis, logistic analysis, Kaplan-Meier curves, and receiver operator characteristic curves to predict biochemical recurrence (BCR). RESULTS: A total of 213 patients with iPCa were selected according to the patient selection protocol. Among them, pathological findings showed that Gleason score (GS) G6, G7 and ≥ G8 were present in 115 cases (54.0%), 78 cases (36.6%), and 20 cases (9.4%), respectively. Further, extracapsular extension (ECE), positive surgical margins (PSM), and lymphovascular invasion (LVI) were present in 28 (13.1%), 18 (8.5%), and 3 cases (1.4%), respectively. Seminal vesicle invasion (SVI) was observed in one case (0.5%). During a median follow-up time of 51 months, BCR was observed 29 cases. Adverse pathology (AP) was defined as GS ≥8, ECE, SVI and LVI. AP and prostate specific antigen (PSA) were significantly associated with BCR. Moreover, PSA > 6.2 ng/ml was suggested as a cut-off value for predicting BCR. CONCLUSIONS: In our results, cases of iPCa had clinically significant PCa, and AP and poor prognosis were also observed in some. Additionally, we found that PSA is the most clinically reliable predictor of oncologic outcome. We suggest that active treatment and diagnosis should be considered for patients with iPCa with PSA > 6.2 ng/ml.

Predictors of adverse pathologic features after radical prostatectomy in low-risk prostate cancer.

BACKGROUND: Prostate-specific antigen (PSA) screening more frequently detects early stage prostate cancer (PC). However, adverse pathologic features (APFs) after radical prostatectomy (RP) in low-risk PC occur. Previous related studies had utilized outdated staging criteria or small sample cohorts. In this study, we analyzed predictors of APFs after RP in low-risk PC using classification under the current criteria. MATERIALS AND METHODS: We retrospectively reviewed medical records of 546 low-risk PC patients who had undergone RP. Low-risk PC was defined as PC with clinical T1-T2a, Gleason score ≤ 6, and PSA levels < 10 ng/mL. Clinical and pathological parameters were analyzed to predict APFs. APFs were defined as extracapsular extension (ECE), seminal vesicle invasion (SVI), or positive surgical margins (PSM). We analyzed our data using univariable and multivariable logistic regression analyses, as well as receiver operator characteristics to predict APFs. RESULTS: Among 546 patients, ECE, SVI, and PSM were present in 199 (36.4%), 8 (1.5%), and 179 cases (32.8%), respectively. PSM had a significant correlation with preoperative high PSA levels and number of positive cores obtained. ECE/SVI was also significantly correlated with PSA levels and number of positive cores. As a result, presence of APFs after RP was associated with high PSA levels and large number of positive cores. PSA > 4.5 ng/mL and number of positive cores > 2 in low-risk PC were significantly associated with APFs, and suggested as cut-off values for predicting APFs. CONCLUSIONS: PSA > 4.5 ng/mL and number of positive cores > 2 in low-risk PC were associated with presence of APFs and patients with such records should be considered carefully to provide active surveillance.

Prognostic implications of polycomb proteins ezh2, suz12, and eed1 and histone modification by H3K27me3 in sarcoma.

BACKGROUND: Polycomb repressive complex 2 (PRC2; formed by EZH2, SUZ12, and EED protein subunits) and PRC1 (BMI1 protein) induce gene silencing through histone modification by H3K27me3. In the present study, we characterized the PRC expression pattern and its clinical implication in sarcoma. METHODS: Using immunohistochemistry, we analyzed PRC expression in 105 sarcoma patients with 5 subtypes: synovial sarcoma (n = 18), rhabdomyosarcoma (n = 28), Ewing sarcoma (n = 15), osteosarcoma (n = 30), and others (n = 14). RESULTS: The median age at diagnosis in the patient cohort was 26.8 years (range: 1-78 years) and the male-to-female ratio was 1:4. Initial disease presentation was locoregional disease in 83% of patients and initial metastatic disease in the remaining 17%. PRC expression was not significantly different according to histologic subtype (P = 0.400). Overall survival (OS) was significantly poor for SUZ12 high (P = 0.001), EED1 high (P = 0.279), and H3K27me3 high (P = 0.009). Ultimately, patients with PRC2high had significantly inferior OS than the no expression group (P = 0.009). In the Cox proportional hazard model adjusted for stage, histologic grade, surgery, margin and initial metastasis, SUZ12 expression (P = 0.020, HR 29.069, 95% CI 1.690-500.007), H3K27me3 (P = 0.010, HR 3.743, 95% CI 1.370-10.228) expression was significantly associated with shorter OS. CONCLUSION: We detected PRC expression in various sarcomas and demonstrated its independent negative prognostic role, suggesting the PRC axis as promising therapeutic target for treating sarcoma.

Retzius-sparing robot-assisted radical prostatectomy using the Revo-i robotic surgical system: surgical technique and results of the first human trial.

OBJECTIVE: To evaluate the safety and proficiency of the Revo-i® robotic platform (Meere Company Inc.) in the treatment of prostate cancer (PCa). PATIENTS AND METHODS: A prospective study was carried out on 17 patients with clinically localized PCa treated between 17 August 2016 and 23 February 2017 at our urology department using the Revo-i. Patients underwent Retzius-sparing robot-assisted radical prostatectomy (RS-RARP). The primary objective was to describe the RS-RARP step-by-step surgical technique using the Revo-i. In addition, the safety of the Revo-i was assessed according to intra-operative and the postoperative complications within 30 days of surgery. Early oncological outcomes were also assessed according to surgical margin status and biochemical recurrence (BCR). Continence was defined as use of no or only one pad. Surgeons' satisfaction with the Revo-i was assessed using the Likert scale. RESULTS: All surgeries were completed successfully, with no conversion to open or laparoscopic surgery. The median patient age was 72 years. The median docking time, console time, urethrovesical anastomosis time and estimated blood loss were 8 min, 92 min, 26 min and 200 mL, respectively. One patient was transfused intra-operatively as a result of blood loss of 1 500 mL. Postoperatively, two patients received blood transfusion, and there were no other serious/major complications. The median hospital stay was 4 days. At 3 months, four patients had positive surgical margins, one patient had BCR, and 15 patients were continent. Most of surgeons were satisfied with the Revo-i performance. CONCLUSIONS: The first human study for the treatment of patients with localized PCa using the Revo-i robotic surgical system was carried out successfully. The peri-operative, early oncological and continence outcomes are encouraging. Further prospective studies are warranted to support our preliminary results.

Does robot-assisted radical prostatectomy benefit patients with prostate cancer and bone oligometastases?

OBJECTIVE: To investigate the peri-operative and oncological outcomes of robot-assisted radical prostatectomy (RARP) in patients with oligometastatic prostate cancer (PCa). PATIENTS AND METHODS: We retrospectively reviewed the records of 79 patients with oligometastatic PCa treated with RARP or androgen deprivation therapy (ADT) between 2005 and 2015 at our institution. Of these 79 patients, 38 were treated with RARP and 41 were treated with ADT without local therapy. Oligometastatic disease was defined as the presence of five or fewer hot spots detected by preoperative bone scan. We evaluated peri-operative outcomes, progression-free survival (PFS), and cancer-specific survival (CSS). We analysed data using Kaplan-Meier methods, with log-rank tests and multivariate Cox regression models. RESULTS: Patients treated with RARP experienced similar postoperative complications to those previously reported in RP-treated patients, and fewer urinary complications than ADT-treated patients. PFS and CSS were longer in RARP-treated compared with ADT-treated patients (median PFS: 75 vs 28 months, P = 0.008; median CSS: not reached vs 40 months, P = 0.002). Multivariate analysis further identified RARP as a significant predictor of PFS and CSS (PFS: hazard ratio [HR] 0.388, P = 0.003; CSS: HR 0.264, P = 0.004). CONCLUSIONS: We showed that RARP in the setting of oligometastatic PCa is a safe and feasible procedure which improves oncological outcomes in terms of PFS and CSS. In addition, our data suggest that RARP effectively prevents urinary tract complications from PCa. The study highlights results from expert surgeons and highly selected patients that cannot be extrapolated to all patients with oligometastatic PCa; to confirm our findings, large, prospective, multicentre studies are required.