Robot-assisted single-port retroperitoneal partial nephrectomy with a novel purpose-built single-port robotic system with deformable surgical instruments.

OBJECTIVE: To investigate the safety and feasibility of using a novel purpose-built single-port robotic system (the SHURUI Robotic Surgical System) with deformable surgical instruments to perform retroperitoneal single-port partial nephrectomy. MATERIALS AND METHODS: A prospective study was conducted to recruit patients with a single renal tumor no more than 4 cm. Robot-assisted single-port partial nephrectomy was performed by using the novel purpose-built single-port robotic system with deformable surgical instruments. Patients' demographics, tumor characteristics, and perioperative parameters were recorded and analyzed. RESULTS: Sixteen patients were recruited to the study. The median tumor size was 2.0 cm (IQR: 1.2-2.4 cm). The median R.E.N.A.L score was 6 (IQR: 4-4.5). In 3 cases, pure single-port surgery was carried out, and all the assistance was through the robotic port. Median docking time was 15.5 min (IQR: 14.25-22.25 min). Median operating time was 148.5 min (IQR: 178-238.5 min). Median console time was 107 min (IQR: 92.75-149.75 min). Median warm ischemic time was 26.5 min (IQR: 24.5-30 min). Median blood loss was 17.5 ml (IQR: 10-50 ml). CONCLUSIONS: Retroperitoneal partial nephrectomy can be safely performed with this novel purpose-built single-port robotic system (SHURUI) with deformable surgical instruments. Further studies are needed to fully evaluate the role of this new platform.

Prognostic Significance of Grade Discrepancy Between Primary Tumor and Venous Thrombus in Nonmetastatic Clear-cell Renal Cell Carcinoma: Analysis of the REMEMBER Registry and Implications for Adjuvant Therapy.

BACKGROUND: Further stratification of the risk of recurrence of clear-cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) will facilitate selection of candidates for adjuvant therapy. OBJECTIVE: To assess the impact of tumor grade discrepancy (GD) between the primary tumor (PT) and VTT in nonmetastatic ccRCC on disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of a multi-institutional nationwide data set for patients with pT3N0M0 ccRCC who underwent radical nephrectomy and thrombectomy. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Pathology slides were centrally reviewed. GD, a bidirectional variable (upgrading or downgrading), was numerically defined as the VTT grade minus the PT grade. Multivariable models were built to predict DFS, OS, and CSS. RESULTS AND LIMITATIONS: We analyzed data for 604 patients with median follow-up of 42 mo (excluding events). Tumor GD between VTT and PT was observed for 47% (285/604) of the patients and was an independent risk factor with incremental value in predicting the outcomes of interest (all p < 0.05). Incorporation of tumor GD significantly improved the performance of the ECOG-ACRIN 2805 (ASSURE) model. A GD-based model (PT grade, GD, pT stage, PT sarcomatoid features, fat invasion, and VTT consistency) had a c index of 0.72 for DFS. The hazard ratios were 8.0 for GD = +2 (p < 0.001), 1.9 for GD = +1 (p < 0.001), 0.57 for GD = -1 (p = 0.001), and 0.22 for GD = -2 (p = 0.003) versus GD = 0 as the reference. According to model-converted risk scores, DFS, OS, and CSS significantly differed between subgroups with low, intermediate, and high risk (all p < 0.001). CONCLUSIONS: Routine reporting of VTT upgrading or downgrading in relation to the PT and use of our GD-based nomograms can facilitate more informed treatment decisions by tailoring strategies to an individual patient's risk of progression. PATIENT SUMMARY: We developed a tool to improve patient counseling and guide decision-making on other therapies in addition to surgery for patients with the clear-cell type of kidney cancer and tumor invasion of a vein.

Single-Port Robot-Assisted Radical Prostatectomy with the Novel Shurui Single-Port Robotic Surgical System.

Purpose: The aim of this study was to explore the safety and efficacy of radical prostatectomy with a novel Shurui single-port (SR-SP) robotic surgical system. Methods: A total of 11 patients with prostate cancer were enrolled in this study. Extraperitoneal radical prostatectomy was performed using the SR-SP robotic surgical system for all patients. Clinicopathologic data, perioperative data, and short-term surgical outcomes were prospectively collected and analyzed. Results: Of the 11 patients, the median age was 65 years (range 52-73), and the median body mass index was 22.6 kg/m2 (range 20.2-26.7). The median operative time was 229 minutes (range 194-317), and the median console time was 167 minutes (range 141-265). The median blood loss was 40 mL (range 10-120), and none of the patients required intraoperative transfusion. There was no conversion to open surgery during the operation, and no assistant ports were added. The surgeons reported a good task load rating with a National Aeronautics and Space Administration Task Load Index (NASA-TLX) score of 25.1 ± 3.3 points. The median postoperative hospital stay time was 7 days (range 4-15). There were no severe intraoperative or postoperative complications (Clavien grade ≥3). Postoperative positive surgical margin occurred in 4 (36.4%) patients. No biochemical recurrence occurred within 1 month of surgery. The continence rate was 72.7% (8/11) 1 month after surgery. Conclusions: The new SR-SP robotic surgical system is safe, effective, flexible, and stable for application in radical prostatectomy.

Development and validation of a prognostic model incorporating tumor thrombus grading for nonmetastatic clear cell renal cell carcinoma with tumor thrombus: A multicohort study.

There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole-exome sequencing on normal-tumor-thrombus-metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C-index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501-0.610, 0.667 versus 0.544-0.651, and 0.719 versus 0.511-0.700 for Training, China-Validation, and Poland-Validation cohorts, respectively). We constructed a risk predicting model, TT-GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT-GPS score displayed better discriminatory ability (OS, c-index: 0.706-0.840, AUC: 0.788-0.874; DFS, c-index: 0.691-0.717, AUC: 0.771-0.789) than previously reported models in risk assessment. In conclusion, we identified for the first-time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT-GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.

Preliminary Experience of Partial Nephrectomy Through a New Single-Port Surgical Robot System.

Purpose: To explore the preliminary safety and efficacy of the Shurui single-port (SP) surgical robot in partial nephrectomy (PN). Methods: This study prospectively enrolled patients with T1a renal tumors who met the inclusion criteria from February to July 2022 in The First Affiliated Hospital School of Medicine Zhejiang University. The operative outcomes and perioperative data, including clinical and histological data, were prospectively collected and analyzed. Results: A total of 13 patients were included in this study, including 7 males and 6 females. The median age was 53 (33-74) years, and the average body mass index was 24.9 ± 4.2 kg/m2. There were 6 cases of left kidney tumors and 7 cases of right kidney tumors in the 13 patients. The average tumor diameter was 1.9 ± 0.9 cm. In all operations, the diseased tissue was removed according to the established surgical plan. The average warm ischemia time was 26.2 ± 9.7 minutes; the average device docking time was 3.6 ± 1.8 minutes; and the average robotic arm operation time was 124.7 ± 40.4 minutes. All operations were successfully completed; there was no conversion to open surgery during the operation; and no operation holes were added. The National Aeronautics and Space Administration Task Load Index (NASA-TLX) score was 26.3 ± 2.6 points, and no device-related adverse events occurred during the operation. The median time to discharge was 6 days (range, 4-11 days). Postoperative pathological examination showed that all tumor margins were negative. There were no Clavien grade ≥3 surgical complications in any of the patients during the perioperative period or at the 1-month postoperative follow-up. Conclusion: The new SP surgical robot system is safe, effective, flexible, and stable for application in PN.

Ganoderma lucidum polysaccharide ameliorated diabetes mellitus-induced erectile dysfunction in rats by regulating fibrosis and the NOS/ERK/JNK pathway.

Background: Diabetes mellitus-induced erectile dysfunction (DMED) is a frequent complication of diabetes mellitus (DM), with limited therapy at present. This study aimed to explore the role and mechanism of Ganoderma lucidum polysaccharide (GLP) on DMED. Methods: DMED was induced in the experimental rats [male 12-week-old Sprague-Dawley (SD) rats] by treatment with streptozotocin (60 mg/kg) and apomorphine (APO). Next, rats in the GLP low dose (GLP-L)/GLP high dose (GLP-H) groups were treated with GLP (100 or 400 mg/kg/d, respectively) for 8 weeks. Subsequently, erectile function was assessed by APO and electrostimulation of the cavernous nerve (CN). Serum or penile testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and cyclic guanosine monophosphate (cGMP) contents were evaluated by enzyme-linked immunosorbent assay (ELISA). The levels of oxidative stress indicators in the corpus cavernosum (CC) were measured by corresponding kits, and histological changes in the CC were observed by hematoxylin-eosin (HE) and Masson staining. Additionally, the apoptosis index, caspase-3, caspase-9, and eNOS expression, and mitochondrial membrane potential (MMP) were also detected. Furthermore, quantitative polymerase chain reaction (qPCR) and western blot assays were conducted to determine the NOS, TGF-ß1 mRNA expression, ERK1/2, eNOS, JNK phosphorylation, and arginase II protein expression. Results: The erectile function test revealed that erectile dysfunction (ED) was alleviated in the DMED rats following treatment with GLP. Moreover, GLP upregulated the T and cGMP content, improved the oxidative stress and histological injuries of CC, and also inhibited the apoptosis and MMP loss of penile tissues in DMED rats. Furthermore, GLP treatment enhanced the mRNA expression of NOS and TGF-ß1 and suppressed the phosphorylation of ERK1/2, eNOS, and JNK, as well as the protein expression of arginase II in DMED rats. Conclusions: GLP ameliorated DMED by repairing the CC pathological damage and upregulating NOS expression and ERK/JNK phosphorylation, indicating that GLP may be a candidate drug for DMED therapy.

Retroperitoneal robot-assisted resection of a lower posterior mediastinal benign schwannoma using a transdiaphragmatic approach: A case report.

INTRODUCTION: Neurogenic tumors are the most frequent neoplasms of the lower posterior mediastinum. Traditionally, lower posterior mediastinal tumors are excised by video-assisted thoracic surgery. However, the available robotic treatment for the lower posterior mediastinum tumors to date are rare. Herein, we report a case of a right lower posterior mediastinal tumors successfully treated with retroperitoneal robot-assisted surgery using a transdiaphragmatic approach. PATIENT CONCERNS: A 54-year-old male patient without any symptoms was admitted into our department with a right lower posterior mediastinal paravertebral tumor that was detected during a medical check-up. DIAGNOSIS: A right lower posterior mediastinal paravertebral tumor. INTERVENTIONS: Retroperitoneal robot-assisted resection using a transdiaphragmatic approach was performed. OUTCOMES: The patient was treated with retroperitoneal robot-assisted surgery using a transdiaphragmatic approach and remained disease-free throughout a 6-month follow-up. His postoperative course was uneventful. Histopathological examination revealed a benign schwannoma. CONCLUSION: Our initial experience showed that retroperitoneal robot-assisted resection of a lower posterior mediastinal tumor using a transdiaphragmatic approach is technically feasible and can be considered a potential alternative for either video-assisted thoracic surgery or a thoracotomy.

Robot-Assisted Laparoscopic Excision of Complicated Retroperitoneal Tumors with Four Arms Via Retroperitoneal Way: A Unique Minimal-Invasive Approach.

Background: Surgical management of complicated retroperitoneal mass is one of the most challenging urologic oncologic surgeries. This study aims to describe our technique and experience in dealing with retroperitoneal mass. Methods: Three patients with complicated retroperitoneal mass were treated with robot-assisted surgery with four arms through retroperitoneal approach. Surgical Procedure: Our standardized anatomic-based "kidney safe first, then mass resection" technique for robot-assisted complicated retroperitoneal mass resection focused on minimizing the chance of renal pedicle injury. Baseline demographics, pathology data, and latest follow-up outcome were obtained. Results: In this retrospectively reviewed case series, all 3 patients were successfully treated with robot-assisted surgery with four arms during retroperitoneal space. One patient received paravertebral mass resection 2 weeks after the robotic surgery. Mean data included operative time of 175 minutes, estimated blood loss was 133 mL, and hospital stay was 4 days. No complications occurred. Conclusions: Robot-assist surgery for complicated retroperitoneal mass with four arms is a safe and feasible way. Patient Summary: Mini-invasive treatment for retroperitoneal mass with robotic four arms through retroperitoneal approach is a feasible way. The approach reduces interruption of intracorporeal structure and organs. And patients could benefit from the retroperitoneal approach with a quicker recovery.

The margin strategy in laparoscopic partial nephrectomy with selective renal artery clamping: Anatomical basis, surgical technique and comparative outcomes.

OBJECTIVE: To evaluate the possibility and efficiency of a modified margin strategy in laparoscopic partial nephrectomy with selective renal artery clamping. METHODS: Seventy-six cases of laparoscopic partial nephrectomy with segmental renal artery clamping in Shanghai Changhai Hospital between July 2014 and September 2017 were retrospectively reviewed. Relevant clinical data were recorded including baseline patient and tumor characteristics, and surgical outcomes (segmental artery mobilization time, operating time, warm ischemic time, estimated blood loss, complications, and so on). A comparative analysis between standard technique and margin strategy was performed. RESULTS: In 38 cases, margin strategy to mobilize segmental artery was successfully performed. In the other 38 cases, the surgery was performed in traditional method. The use of new strategy led to a shortened segmental artery mobilization time (5 min vs 12 min, p < 0.001). There was no difference in terms of perioperative complications between the two techniques. CONCLUSIONS: The margin strategy is a practical method in laparoscopic partial nephrectomy with selective renal artery clamping. It provides a simplified way of finding segmental arteries. Further studies are needed to confirm these preliminary findings.

Retroperitoneal robot-assisted laparoscopic upper pole heminephrectomy in adult patients with duplex kidneys.

Background: To report our experience with retroperitoneal robot-assisted laparoscopic upper pole heminephrectomy in adult patients with duplex kidneys. Methods: We retrospectively reviewed the medical records of 7 patients who underwent retroperitoneal robot-assisted laparoscopic upper pole heminephrectomy at our institution between September 2014 and July 2017. Of the robot-assisted laparoscopic procedures, 5 were on the left and 2 on the right side. Results: All patients underwent robot-assisted laparoscopic surgery successfully in a totally retroperitoneal manner without conversion to open surgery. The mean operative time was 175 mins (range 140-270). The mean estimated blood loss was 84 mL (range 20-200). The mean postoperative hospital stay was 7 days (range 5-9). No major intraoperative and postoperative complications occurred. All patients had a resolution of their presenting symptoms after surgery at a mean follow-up of 24 months (range 14-38). Conclusion: Our initial clinical experience suggests that robot-assisted laparoscopic upper pole heminephrectomy using a retroperitoneal approach for a duplex kidney appears to be safe with acceptable perioperative outcomes.

Protective effect of urolithin a on cisplatin-induced nephrotoxicity in mice via modulation of inflammation and oxidative stress.

Limitation of widely used anti-cancer agent cisplatin for a patient is nephrotoxicity. Nephrotoxicity is presentable in mice by injecting cisplatin at 25 mg/kg with 3 days endpoint. We used the same model to understand the protective role of urolithin A. Cisplatin-induced renal damages measured by histological damage in proximal tubular cells and by the increase in serum neutrophil gelatinase-associated lipocalin (NGAL), blood urea nitrogen (BUN), creatinine and urinary Kidney Injury Molecule-1 (KIM-1). Urolithin A pretreatment reduced all the above renal damage parameters in a significant way. Urolithin A attenuated cisplatin-induced pro-inflammatory cytokine/chemokine tumor necrosis factor α (TNFα), interleukin 23 (IL-23), interleukin 18 (IL-18) and macrophage inflammatory protein 2 (MIP2). Cisplatin-induced CD11b positive macrophages in kidneys reduced by urolithin A. Urolithin A also attenuated cisplatin-induced renal oxidative/nitrative stress, which was measured by lipid peroxidation(4-hydroxy-2-nonenal or 4-HNE protein adducts) and protein nitration. Urolithin A cisplatin-induced kidney injury in mice through the down regulation of inflammatory cytokines/chemokine, immune cells, and oxidative/nitrative stress thus improving cisplatin-induced proximal tubular cell death.

Robotic-assisted Urethra-sparing Simple Prostatectomy Via an Extraperitoneal Approach.

OBJECTIVE: To present an original technique of robotic-assisted urethra-sparing simple prostatectomy (RAUSP) for treating patients with benign prostatic hyperplasia. MATERIALS AND METHODS: From April 2015 to December 2016, 27 patients underwent RAUSP via an extraperitoneal approach. Baseline patient characteristics, perioperative outcomes, pathologic outcomes, postoperative Clavien complications, International Prostate Symptom Score, International Index of Erectile Function, and ejaculatory function were assessed. RESULTS: Twenty-six patients (96.3%) successfully underwent RAUSP, one patient (3.7%) was converted to simple prostatectomy. Median operative time was 169 minutes (interquartile range: 150-185); median estimated blood loss was 235 mL (interquartile range: 180-300). Seven cases (26.9%) required urethral repair secondary to inadvertent urethrotomy. Mean catheterization time was 1.6 days (range 1-5). Clavien complications were reported, 6 being low grade (grade 1 or 2) with a single 3a complication (gross hematuria requiring bladder irrigation). Mean follow-up duration was 16.4 months (range 9-30). Postoperative questionnaire demonstrated that international prostate symptom score (P < .001) and quality of life score (P < .001) were significantly improved postoperatively. A total of 14 patients reported erectile function, 13 of which had normal ejaculation, only 1 complained retrograde ejaculation. CONCLUSION: RAUSP is technically feasible for patients with benign prostatic hyperplasia. Our data indicate that patients have short catheterization time, an acceptable risk profile, significant improvements of voiding function and maintaining antegrade ejaculation following this urethral-sparing technique.

Extraperitoneal robot-assisted laparoscopic retroperitoneal lymph node dissection for early-stage testicular nonseminomatous germ cell tumors: A case report and literature review.

RATIONALE: Typically robot-assisted laparoscopic retroperitoneal lymph node dissection (R-RPLND) has been performed via a transperitoneal approach. Herein we report the first case of a novel R-RPLND using an extraperitoneal approach. PATIENT CONCERNS: A 38-year-old man presented with an enlarging right scrotal mass. DIAGNOSES: Scrotal ultrasonography demonstrated a 5.5-cm solid mass of the right testis. The patient underwent right radical inguinal orchiectomy. Pathologic examination demonstrated a mixed germ cell tumor, predominately embryonal carcinoma with yolk sac tumor. INTERVENTIONS: Extraperitoneal R-PRLND was performed 3 weeks after the radical orchiectomy. OUTCOME: The final pathologic examination showed a count of 19 lymph nodes, all of them negative. Normal antegrade ejaculation returned within 4 weeks postoperatively. No retroperitoneal recurrence or elevation of tumor marker levels were seen via surveillance imaging. LESSONS: Our study shows that extraperitoneal R-RPLND is a safe and feasible procedure using an extraperitoneal approach that provides minimal invasion and rapid recovery of patients.

A Novel Retrieval Technique for Ureteral Stents Under Ultrasound Guidance in Male Patients.

OBJECTIVE: To simply retrieve double-J stents in male patients under ultrasound guidance, a novel technique is developed and evaluated for efficiency, safety, and tolerability. METHODS: Fifty-six male patients, ranging in age from 23 to 65 years old, were recruited from March to December 2015. Thirty patients (32 stents) underwent double-J stent retrieval by ultrasound guidance and 26 patients (28 stents) underwent cystoscopy retrieval separately. Clinical outcomes were compared between groups. Hematuria and leukocytosis were assessed every day postoperatively. A visual analog pain scale on a scale of 0-10 was used to assess procedure-related pain. RESULTS: In the experimental group, 87.5% of ureteral stents were successfully removed. Using our novel technique without any local anesthesia, male patients experienced less pain compared with the cystoscopy group significantly (P < .001). The majority of complications were microscopic hematuria (39.28%), less than that in the cystoscopy group (69.23%, P = .027). Meanwhile, only few patients have leukocytosis in both groups (14.3% vs 11.5%, P > .05). Average procedure time was 7.35 ± 2.59 minutes longer than that of the standard group (5.13 ± 1.29 minutes; P < .001). However, it had been improved with increasing experience (r = 0.618, P < .001). In addition, this novel technique is cost-effective for clinical practice. CONCLUSION: This is the first study to assess the possibility of ultrasound-guided retrieval technique in male patients. The safety and success rate of this new technique is similar to that of a conventional procedure. Whereas it is tolerable and cost effective for male and disabled patient bear with lithotomy position.

Prostate cancer antigen 3 moderately improves diagnostic accuracy in Chinese patients undergoing first prostate biopsy.

Prostate cancer antigen 3 (PCA3) is a biomarker for diagnosing prostate cancer (PCa) identified in the Caucasian population. We evaluated the effectiveness of urinary PCA3 in predicting the biopsy result in 500 men undergoing initial prostate biopsy. The predictive power of the PCA3 score was evaluated by the area under receiver operating characteristic (ROC) curve (AUC) and by decision curve analysis. PCA3 score sufficed to discriminate positive from negative prostate biopsy results but was not correlated with the aggressiveness of PCa. The ROC analysis showed a higher AUC for the PCA3 score than %fPSA (0.750 vs 0.622, P = 0.046) in patients with a PSA of 4.0-10.0 ng ml-1 , but the PCA3-based model is not significantly better than the base model. Decision curve analysis indicates the PCA3-based model was superior to the base model with a higher net benefit for almost all threshold probabilities, especially the threshold probabilities of 25%-40% in patients with a PSA of 4.0-10.0 ng ml-1 . However, the AUC of the PCA3 score (0.712) is not superior to %fPSA (0.698) or PSAD (0.773) in patients with a PSA >10.0 ng ml-1 . Our results confirmed that the RT-PCR-based PCA3 test moderately improved diagnostic accuracy in Chinese patients undergoing first prostate biopsy with a PSA of 4.0-10.0 ng ml-1 .

Robotic-assisted Laparoscopic Transposition of the Left Renal Vein for Treatment of the Nutcracker Syndrome.

Nutcracker syndrome is a rare condition of left renal vein entrapment manifesting with hematuria and flank pain. We report a case of nutcracker syndrome, where a robotic-assisted laparoscopic transposition of the left renal vein was performed. To our knowledge, this is the first case of robotic-assisted laparoscopic surgery of a nutcracker syndrome.

Clinical utility of a novel urine-based gene fusion TTTY15-USP9Y in predicting prostate biopsy outcome.

OBJECTIVE: In recent years, great effort has been made to explore new biomarkers for early detection of prostate cancer. Our previous study has demonstrated the high prevalence of TTTY15-USP9Y in prostate cancer samples from a Chinese population. Our aim was to evaluate the clinical utility of TTTY15-USP9Y in predicting the prostate biopsy outcome. MATERIALS AND METHODS: We retrospectively examined the expression of TTTY15-USP9Y in 226 qualified urine sediment samples. Total RNA was extracted from the urine sediment by using TRIzol reagent, and complementary DNA was synthesized using TransPlex Complete Whole Transcriptome Amplification Kit (WTA2). Real-time quantitative polymerase chain reaction was performed to evaluate the expression of TTTY15-USP9Y and the prostate cancer-specific antigen (PSA) level. The TTTY15-USP9Y score was calculated as 2(Ct(PSA)-Ct(TTTY15-USP9Y))× 1,000. RESULTS: The TTTY15-USP9Y score was statistically significantly higher in men with positive biopsy outcome than in men with negative biopsy outcome (P<0.001). The area under the curve was 0.828 for the TTTY15-USP9Y score in the entire patient cohort. The TTTY15-USP9Y score׳s cutoff of 90.28 provided the optimal balance between sensitivity (84.0%) and specificity (77.5%). The combination of PSA level and the TTTY15-USP9Y score significantly improved the diagnostic performance of PSA level (P = 0.001). The TTTY15-USP9Y score alone was superior to PSA level, percent free PSA, and PSA density (serum PSA/prostate volume) in the subgroup of clinical interest (PSA level: 4-10ng/ml, gray zone). Univariable and multivariable logistic analyses indicated that TTTY15-USP9Y score, PSA level, age, and prostate volume were independent predictors of PCa. Adding the TTTY15-USP9Y score in the clinical base model (PSA level, age, and prostate volume) could bring a higher net benefit and reduce more unnecessary biopsies in the defined range of interest (10%-40% threshold probability). CONCLUSION: In conclusion, our study explored the potential utility of measuring the TTTY15-USP9Y score in post-digital rectal examination urine samples to predict biopsy outcome and provided the basis for the utility of this novel gene fusion in multicenter and large cohort studies.

A novel urinary long non-coding RNA transcript improves diagnostic accuracy in patients undergoing prostate biopsy.

BACKGROUND: Long non-coding RNA (LncRNA) PCA3 has been a well-established urine biomarker for the detection of prostate cancer (PCa). Our previous study showed a novel LncRNA FR0348383 is up-regulated in over 70% of PCa compared with matched benign tissues. The aim of this study was to evaluate the diagnostic value of urinary FR0348383 for men undergoing prostate biopsy due to elevated PSA (PSA > 4.0 ng/ml) and/or abnormal digital rectal examination (DRE). METHODS: Post-DRE first-catch urine specimens prior to prostate biopsies were prospectively collected. After the whole transcriptome amplification, quantitative real time polymerase chain reaction was applied to quantify urine FR0348383 and PSA levels. The FR0348383 score was calculated as the ratio of PSA and FR0348383 mRNA (PSA mRNA/FR0348383 mRNA × 1000). The diagnostic value of FR0348383 score was evaluated by logistic regression and decision curve analysis. RESULTS: 213 cases with urine samples containing sufficient mRNA were included, 94 cases had serum PSA level 4.0-10.0 ng/ml. PCa was identified in 72 cases. An increasing FR0348383 score was correlated with an increasing probability of a positive biopsy (P < 0.001). Multivariable logistic analysis indicated FR0348383 score (P < 0.001), PSA (P = 0.004), age (P = 0.007), prostate volume (P < 0.001) were independent predictors of PCa. ROC analysis demonstrated FR0348383 score outperformed PSA, %free PSA, and PSA Density in the prediction of PCa in the subgroup of patients with grey area PSA (AUC: 0.815 vs. 0.562 vs. 0.599 vs. 0.645). When using a probability threshold of 30% in the grey zone cohort, The FR0348383 score would save 52.0% of avoidable biopsies without missing any high grade cancers. CONCLUSIONS: FR0348383 transcript in post-DRE urine may be a novel biomarker for detection of PCa with great diagnostic value, especially in the grey zone cohort. The application of FR0348383 score in clinical practice might avoid unnecessary prostate biopsies and increase the specificity of PCa diagnosis.

Development and prospective multicenter evaluation of the long noncoding RNA MALAT-1 as a diagnostic urinary biomarker for prostate cancer.

The current strategy for diagnosing prostate cancer (PCa) is mainly based on the serum prostate-specific antigen (PSA) test. However, PSA has low specificity and has led to numerous unnecessary biopsies. We evaluated the effectiveness of urinary metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), a long noncoding RNA, for predicting the risk of PCa before biopsy. The MALAT-1 score was tested in a discovery phase and a multi-center validation phase. The predictive power of the MALAT-1 score was evaluated by the area under receiver operating characteristic (ROC) curve (AUC) and by decision curve analysis. As an independent predictor of PCa, the MALAT-1 score was significantly higher in men with a positive biopsy than in those with a negative biopsy. The ROC analysis showed a higher AUC for the MALAT-1 score (0.670 and 0.742) vs. the total PSA (0.545 and 0.601) and percent free PSA (0.622 and 0.627) in patients with PSA values of 4.0-10 ng/ml. According to the decision curve analysis, using a probability threshold of 25%, the MALAT-1 model would prevent 30.2%-46.5% of unnecessary biopsies in PSA 4-10 ng/ml cohorts, without missing any high-grade cancers. Our results demonstrate that urine MALAT-1 is a promising biomarker for predicting prostate cancer risk.