A genomic and epigenomic atlas of prostate cancer in Asian populations.

Prostate cancer is the second most common cancer in men worldwide1. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients2,3. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.

Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter, randomized, open-label, phase 2 trial.

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).

Quantum Control of Graphene Plasmon Excitation and Propagation at Heaviside Potential Steps.

Quantum mechanical effects of single particles can affect the collective plasmon behaviors substantially. In this work, the quantum control of plasmon excitation and propagation in graphene is demonstrated by adopting the variable quantum transmission of carriers at Heaviside potential steps as a tuning knob. First, the plasmon reflection is revealed to be tunable within a broad range by varying the ratio γ between the carrier energy and potential height, which originates from the quantum mechanical effect of carrier propagation at potential steps. Moreover, the plasmon excitation by free-space photos can be regulated from fully suppressed to fully launched in graphene potential wells also through adjusting γ, which defines the degrees of the carrier confinement in the potential wells. These discovered quantum plasmon effects offer a unified quantum-mechanical solution toward ultimate control of both plasmon launching and propagating, which are indispensable processes in building plasmon circuitry.

The development of plasma pseudotargeted GC-MS metabolic profiling and its application in bladder cancer.

Bladder cancer (BC) is a fatal malignancy with considerable mortality. BC urinary metabolomics has been extensively investigated for biomarker discovery, but few BC blood metabolomic studies have been performed. Hence, a plasma pseudotargeted metabolomic method based on gas chromatography-mass spectrometry with selected ion monitoring (GC-MS-SIM) was developed to study metabolic alterations in BC. The analytical performance of the developed method was compared with that of a nontargeted method. The relative standard deviation (RSD) values of 89 and 70.7 % of the peaks obtained using the pseudotargeted and nontargeted methods, respectively, were less than 20 %. The Pearson correlations of 90.7 and 78.3 % of the peaks obtained using the pseudotargeted and nontargeted methods, respectively, exceeded 0.90 in the linearity evaluation. Compared with the nontargeted method, the signal-to-noise ratios (S/N) of 97.9 and 69.3 % of the peaks increased two- and fivefold, respectively. The developed method was fully validated, with good precision, recovery, and stability of the trimethylsilyl (TMS) derivatives. The method was applied to investigate BC. Significant increases in the contents of metabolites involved in, for example, the pentose phosphate pathway (PPP) and nucleotide and fatty acid synthesis were found in the high-grade (HG) BC group compared to the healthy control (HC) group. These differences imply that the activated PPP may regulate BC cell proliferation by promoting lipid and nucleotide biosynthesis and the detoxification of reactive oxygen species (ROS). These results illustrate that the plasma pseudotargeted method is a powerful tool for metabolic profiling. Graphical abstract The plasma pseudotargeted metabolic profiling suggested the metabolic alterations in bladder cancer (BC) and the significantly differential metabolites for BC discrimination.

[Surgical treatment of azoospermia caused by iatrogenic injury to bilateral vas deferens].

OBJECTIVE: To investigate the treatment of azoospermia induced by iatrogenic injury to the bilateral vas deferens. METHODS: We retrospectively analyzed 11 cases of azoospermia caused by iatrogenic injury to bilateral vas deferens. The patients were aged 20－33 years, all diagnosed with azoospermia preoperatively and none with a history of pelvic operation. Seven of them had received bilateral inguinal hernia repair and the other 4 undergone bilateral orchidopexy in the childhood. RESULTS: Intraoperative exploration of the bilateral inguinal region was performed in all the patients. Bilateral vas deference atresia was found in the inguinal canal in 6 cases, which was treated by microscopic vasovasostomy following removal of the atresic segment. Vas deferens residual was observed in or near the deep inguinal ring in the other 5 cases, with the distal vas deferens inaccessible, which was treated by bilateral vasovasostomy in 3 cases and unilateral vasovasostomy in 2 (for longer defect segment than could be anastomosed) following combined laparoscopic exploration of the abdominal cavity. The patients were followed up for 3－12 months postoperatively, during which sperm were detected in 7 cases, with sperm concentration ranging from 0.4×106/ml to 35×106/ml and grade a+b sperm from 15% to 46%. CONCLUSIONS: For the diagnosis of azoospermia, especially in patients with no history of pelvic operation, special attention should be paid to iatrogenic injury to the vas deferens. For the treatment of the disease, non-tension vasovasostomy is essential and, when necessary, the vas deferens can be reconstructed by changing its anatomical path and shortening its length.

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.

Propensity-score matched analysis comparing robot-assisted with laparoscopic partial nephrectomy.

OBJECTIVES: To compare the peri-operative and early renal functional outcomes of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) for kidney tumours. MATERIALS AND METHODS: A total of 237 patients fulfilling the selection criteria were included, of whom 146 and 91 patients were treated with LPN and RAPN, respectively. To adjust for potential baseline confounders, propensity-score matching was performed. A favourable outcome was defined as a warm ischaemia time (WIT) of ≤20 min, negative surgical margins, no surgical conversion, no Clavien ≥3 complications and no postoperative chronic kidney disease (CKD) upstaging. Descriptive statistics and multivariable logistic regression analyses were performed before and after propensity-score matching. RESULTS: Within the propensity-score-matched cohort, the RAPN group was associated with significantly lower estimated blood loss (EBL; 156 vs 198 mL, mean difference [MD] = -42; P = 0.025), a shorter WIT (22.8 vs 31 min, MD = -8.2; P < 0.001) and a higher proportion of malignant lesions (88.4 vs 67.5%; odds ratio [OR]: 2.6; 95% confidence interval [CI]: 1.2-5.67; P = 0.023). With regard to early renal functional outcomes, the mean last estimated glomerular filtration rate was 95.8 and 89.4 mL/min per 1.73 m(2) (MD = 6.4; P = 0.01), with a mean ± sd percentage change of -4.8 ± 17.9 and -12.2 ± 16.6 (MD = 7.4; P = 0.018) in the RAPN and LPN groups, respectively. The intra-operative complication rate was significantly lower in the RAPN group (1.3 vs 11.7%; OR 0.1, 95% CI 0.01-0.81; P = 0.018). On multivariable analysis, surgical approach (RAPN vs LPN, OR 5.457, 95% CI 2.075-14.346; P = 0.001), Charlson Comorbidity Index (OR 0.223; 95% CI 0.062-0.811; P = 0.023), diameter-axial-polar score (OR 0.488, 95% CI 0.329-0.723; P < 0.001) and preoperative CKD stage (OR 3.189, 95% CI 1.204-8.446; P = 0.020) were found to be independent predictors of obtaining a favourable outcome. CONCLUSIONS: After adjusting for potential treatment selection biases, RAPN was found to be superior to LPN for peri-operative outcomes (EBL, WIT and intra-operative complications) and early renal functional preservation.

Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer.

PURPOSE: To understand the role of MALAT-1 in prostate cancer we evaluated its expression in prostate cancer tissues and cell lines. We also studied the therapeutic effects of MALAT-1 silencing on castration resistant prostate cancer cells in vitro and in vivo. MATERIALS AND METHODS: Quantitative reverse transcriptase-polymerase chain reaction was used to detect MALAT-1 expression in prostate cancer tissues and cell lines. siRNA against MALAT-1 was designed and the silencing effect was examined by quantitative reverse transcriptase-polymerase chain reaction. The biological effects of MALAT-1 siRNA on cells were investigated by examining cell proliferation using a cell counting kit and cell colony assays as well as cell migration by in vitro scratch assay, cell invasion by Transwell® invasion assay and cell cycle by flow cytometry. We further investigated the effect of therapeutic siRNA targeting MALAT-1 on castration resistant prostate cancer in vivo. RESULTS: MALAT-1 was up-regulated in human prostate cancer tissues and cell lines. Higher MALAT-1 expression correlated with high Gleason score, prostate specific antigen, tumor stage and castration resistant prostate cancer. MALAT-1 down-regulation by siRNA inhibited prostate cancer cell growth, invasion and migration, and induced castration resistant prostate cancer cell cycle arrest in the G0/G1 phases. Importantly, intratumor delivery of therapeutic siRNA targeting MALAT-1 elicited delayed tumor growth and reduced metastasis of prostate cancer xenografts in castrated male nude mice, followed by the concomitant prolongation of survival of tumor bearing mice. CONCLUSIONS: MALAT-1 may be needed to maintain prostate tumorigenicity and it is involved in prostate cancer progression. Thus, MALAT-1 may serve as a potential therapeutic target for castration resistant prostate cancer.

Establishment and characterization of clear cell renal cell carcinoma cell lines with different metastatic potential from Chinese patients.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) cell lines with distinct metastatic potential are essential to study the mechanism of ccRCC metastasis. However, none of them originated from Chinese. METHODS: Primary cell cultures were performed using a primary tumor of a 49-year-old male ccRCC patient and a metastatic tumor of a 62-year-old male patient who had received nephrectomy to excise primary ccRCC 10 years ago. Cell growth, microstructure, cytogenetics, cytometry, expression of metastasis-associated molecules, tumorigenesis and metastasis were subsequently characterized. RESULTS: Two successive cell lines named NRCC from the primary ccRCC and MRCC from the metastatic ccRCC were established, respectively. Compared to NRCC, MRCC exhibited stronger anchorage-independent growth and invasion potentials and contained more glycogen granules in the cytoplasm. Gains of chromosomes and some translocations were the major chromosomal aberrations in both cell strains. CD24 expression was more frequent in MRCC than in NRCC and the same was true for CD56. The transcriptional levels of TNFα, IL-6, VEGF, HIF2α, MMP2, and RhoC were significantly higher in MRCC than in NRCC. Cytosolic IκBα protein was more degraded in MRCC than in NRCC following TNFα treatment. Both cell lines had strong tumorigenicity in athymic nude mice. However, MRCC had strong potential in generating metastasis to lung and hemorrhagic ascites than NRCC following orthotopic transplantations. CONCLUSIONS: Cancer cells isolated from metastatic ccRCC have more malignant and metastatic potential than those from the primary tumor from the patients who shared the similar race background. Establishment of MRCC and NRCC may provide suitable models with which to investigate molecular mechanisms of ccRCC metastasis.

Dishevelled-2 silencing reduces androgen-dependent prostate tumor cell proliferation and migration and expression of Wnt-3a and matrix metalloproteinases.

To identify Dishevelled-2 (Dvl2) is a prostate cancer-associated gene and analyze the effects on the growth and invasive capacity of human prostate cancer (PCa) cells. Dvl2 mRNA expression was measured in PCa cell lines and tissue samples, by real-time reverse transcription PCR (qRT-PCR). Immunohistochemistry was used to examine the distribution of Dvl2 in PCa specimens. Silencing Dvl2 in LNCaP cells, proliferation was measured by the CCK-8 assay, cell motility and invasiveness by scratch wound and transwell migration assays, and Wnt-3a, AR, and matrix metalloproteinase (MMP) expression by western blotting. Dvl2 was overexpressed in LNCaP cells compared with the AI PCa lines DU-145 and PC-3, as well as in the majority of PCa tissue specimens examined by qRT-PCR (14/27, 51.9 %). Dvl2 expression was low in all 10 BPH specimens, weakly positive in 26/104 AD PCa specimens (23.8 %), positive in 60/104 AD PCa specimens (55 %), and strongly positive in all 5 AI PCa specimens. Dvl2 expression was significantly correlated with combined Gleason score (p = 0.02), lymph node metastasis (p = 0.005), and TNM stage (p = 0.015). Silencing of Dvl2 mRNA expression significantly reduced LNCaP cell proliferation, motility, invasiveness and Wnt-3a, AR, MMP-2, and MMP-9 expression. Dvl2 may increase PCa growth and metastasis potential, possibly by upregulating Wnt-3a, AR, and MMP expression. Silencing Dvl2 expression may be an effective treatment strategy for PCa.

Nondecaying long range effect of surface decoration on the charge state of NV center in diamond.

On the basis of density functional theory, stability and electronic structure of nitrogen-vacancy (NV) centers in surface modified diamond have been studied. Surface decoration is traditionally expected to only have influence on those NV centers close to the surface. However, our calculations indicate that its effect to charged NV centers is nondecaying and long-range, where the formation energy of the charged NV center converges to a value typically different for different types of surface decoration. Such a nondecaying long range effect is due to the electrostatic potential shift induced by the surface dipole layer, and it leads to the preference of NV(-) center for oxygen saturated diamond and NV(0) for hydrogenated one. Our work demonstrates that surface functionalization can be used to modify the relative stabilities of differently charged defects in nonmetallic materials.

Polyacrylic Acid/Polyaniline-Coated Multimode Interferometer for Ammonia Detection.

A coaxial optical fiber interferometer (COFI) is proposed here for ammonia sensing, which comprises two light-carrying single-mode fibers (SMF) fused to a section of no-core fiber (NCF), thus forming an optical interferometer. The outer surface of the COFI is coated with a layer of polyacrylic acid (PAA)/polyaniline (PAni) film. The refractive index (RI) of the sensitive layer varies when PAA/PAni interacts with ammonia, which leads to the resonance wavelength shift. The surface morphology and structure of the PAA/PAni composites were characterized by using a scanning electron microscope (SEM) and Fourier-transform infrared (FTIR) spectroscopy. When the sensor was exposed to an ammonia atmosphere of different concentrations at room temperature, the sensing performance of the PAA/PAni composite film was superior to that of a sensitive film formed by single-component PAA or PAni. According to the experimental results, the composite film formed by 5 wt% PAA mixed with 2 wt% PAni shows better performance when used for ammonia sensing. A maximum sensitivity of 9.8 pm/ppm was obtained under the ammonia concentration of 50 ppm. In addition, the sensor shows good performance in response time (100 s) and recovery time (180 s) and has good stability and selectivity. The proposed optical fiber ammonia sensor is adapted to monitor leakage in its production, storage, transportation, and application.

Advanced Integration of Glutathione-Functionalized Optical Fiber SPR Sensor for Ultra-Sensitive Detection of Lead Ions.

It is crucial to detect Pb2+ accurately and rapidly. This work proposes an ultra-sensitive optical fiber surface plasmon resonance (SPR) sensor functionalized with glutathione (GSH) for label-free detection of the ultra-low Pb2+ concentration, in which the refractive index (RI) sensitivity of the multimode-singlemode-multimode (MSM) hetero-core fiber is largely enhanced by the gold nanoparticles (AuNPs)/Au film coupling SPR effect. The GSH is modified on the fiber as the sensing probe to capture and identify Pb2+ specifically. Its working principle is that the Pb2+ chemically reacts with deprotonated carboxyl groups in GSH through ligand bonding, resulting in the formation of stable and specific chelates, inducing the variation of the local RI on the sensor surface, which in turn leads to the SPR wavelength shift in the transmission spectrum. Attributing to the AuNPs, both the Au substrates can be fully functionalized with the GSH molecules as the probes, which largely increases the number of active sites for Pb2+ trapping. Combined with the SPR effect, the sensor achieves a sensitivity of 2.32 × 1011 nm/M and a limit of detection (LOD) of 0.43 pM. It also demonstrates exceptional specificity, stability, and reproducibility, making it suitable for various applications in water pollution, biomedicine, and food safety.

Modulation of nanocavity plasmonic emission by local molecular states of C60 on Au(111).

We investigate the modulation of C60 monolayers on the nanocavity plasmonic (NCP) emission on Au(111) by tunneling electron excitation from a scanning tunneling microscope (STM) tip. STM induced luminescence spectra show not only suppressed emission, but also significant redshift of NCP emission bands on the C60 molecules relative to the bare metal surface. The redshift, together with the bias- and coverage-dependent emission feature, indicates that the C60 molecules act beyond a pure dielectric spacer, their electronic states are heavily involved in the inelastic tunneling process for plasmonic emission. A modified quantum cutoff relation is proposed to explain qualitatively the observed emission feature at both bias polarities. We also demonstrate molecularly resolved optical contrast on the C60 monolayer and discuss the contrast mechanism briefly.

Design and control of electron transport properties of single molecules.

We demonstrate in this joint experimental and theoretical study how one can alter electron transport behavior of a single melamine molecule adsorbed on a Cu (100) surface by performing a sequence of elegantly devised and well-controlled single molecular chemical processes. It is found that with a dehydrogenation reaction, the melamine molecule becomes firmly bonded onto the Cu surface and acts as a normal conductor controlled by elastic electron tunneling. A current-induced hydrogen tautomerization process results in an asymmetric melamine tautomer, which in turn leads to a significant rectifying effect. Furthermore, by switching on inelastic multielectron scattering processes, mechanical oscillations of an N-H bond between two configurations of the asymmetric tautomer can be triggered with tuneable frequency. Collectively, this designed molecule exhibits rectifying and switching functions simultaneously over a wide range of external voltage.

Tracing and Forecasting Metabolic Indices of Cancer Patients Using Patient-Specific Deep Learning Models.

We develop a patient-specific dynamical system model from the time series data of the cancer patient's metabolic panel taken during the period of cancer treatment and recovery. The model consists of a pair of stacked long short-term memory (LSTM) recurrent neural networks and a fully connected neural network in each unit. It is intended to be used by physicians to trace back and look forward at the patient's metabolic indices, to identify potential adverse events, and to make short-term predictions. When the model is used in making short-term predictions, the relative error in every index is less than 10% in the L∞ norm and less than 6.3% in the L1 norm in the validation process. Once a master model is built, the patient-specific model can be calibrated through transfer learning. As an example, we obtain patient-specific models for four more cancer patients through transfer learning, which all exhibit reduced training time and a comparable level of accuracy. This study demonstrates that this modeling approach is reliable and can deliver clinically acceptable physiological models for tracking and forecasting patients' metabolic indices.

Rapid-Response and Wide-Range pH Sensors Enabled by Self-Assembled Functional PAni/PAA Layer on No-Core Fiber.

The measurement of pH has received great attention in diverse fields, such as clinical diagnostics, environmental protection, and food safety. Optical fiber sensors are widely used for pH sensing because of their great advantages. In this work, an optical fiber pH sensor is fabricated, by combining the merits of the multimode interference configuration and pH-sensitive polyaniline/polyacrylic acid (PAni/PAA) coatings, which was successfully in situ deposited on the no-core fiber (NCF) by the layer-by-layer (LBL) self-assembly method. The sensors' performance was experimentally characterized when used for pH detection. It has a high sensitivity of 0.985 nm/pH and a great linear response in a universal pH range of 2-12. The response time and recovery time is measured to be less than 10 s. In addition, its temperature sensitivity is tested to be about 0.01 nm/°C with a low temperature crosstalk effect, which makes it promising for detecting pH in the liquid phase with temperature variation. The sensors also demonstrated easy fabrication, good stability, and repeatability, which are adapted to pH detection in most practical applications.

Propensity-matched pair analysis of safety and efficacy between laparoscopic and open radical nephrectomy for the treatment of large renal masses (>10 cm): a retrospective cohort study.

Background: Open radical nephrectomy (ORN) is a practical procedure for treating patients with large renal carcinomas >10 cm in size, and few studies have focused on feasibility and safety of laparoscopic radical nephrectomy (LRN). The current study was to assess the safety and effectiveness of LRN and ORN in large renal carcinoma patients by propensity matched pair analysis. Methods: In this cohort study, a retrospective review of radical nephrectomy data from October 2010 to October 2018 at Changhai Hospital was conducted. Patients with renal carcinomas >10 cm in size by pre-operative images were included. Patients' demographics including age, gender, body mass index (BMI), tumor size, operation time, hospitalization days, etc. were collected. Renal tumor patients undergoing LRN or ORN were match-paired by gender, BMI, age, and tumor size. Peri-operative outcomes including estimated blood loss and complications were compared. The follow-up contents included survival time, disease progression, and cause of death, and cancer-specific and progression-free survival were estimated via Kaplan-Meier curve analysis. Results: Among 92 patients with clinical T2b renal masses, 37 pairs were matched. The average tumor sizes of the LRN and ORN groups were 11.37±0.30 and 11.67±0.33 cm (P=0.375), respectively. The average operating time for LRN was slightly longer (204.32±11.17 vs. 192.78±8.50 min, P=0.414). Estimated blood loss (EBL) (336.49±63.58 mL for LRN vs. 545.95±74.52 mL for ORN, P=0.036), the length of postoperative stay [6.0 (5.0-9.0) for LRN vs. 9.0 (6.0-11.5) days for ORN, P=0.015], and removal time of the drainage tube [4.0 (3.0-5.0) days for LRN vs. 5.0 (4.0-6.0) for ORN, P<0.001] were less than in the LRN group. The pathological subtype and Fuhrman grade were comparable. Both groups were followed up for a similar period, and no difference was observed in 5-year survival rates. Conclusions: Considering the conversion rates and overall complication rates, it seems that LRN for large renal carcinomas demonstrated equivalent peri-operative safety and effectiveness compared with ORN, with no adverse effects on midterm oncological outcomes.

D9S168 microsatellite alteration predicts a poor prognosis in patients with clear cell renal cell carcinoma and correlates with the down-regulation of protein tyrosine phosphatase receptor delta.

BACKGROUND: The role of microsatellite alterations in surgically excised tumors in predicting the prognosis of patients with clear cell renal cell carcinoma (ccRCC) remains largely unknown. METHODS: Specimens from 93 patients with sporadic ccRCC were used to screen microsatellite alterations using 12 markers on chromosomes 3p, 9p, and 14q according to disease stage. Survival was evaluated by using the Kaplan-Meier method and Cox regression analysis. The expression of targeted genes was examined using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. RESULTS: Of the markers that were screened, D9S168 (9p23-22) had the highest frequency (36.9%) of microsatellite alteration in the specimens. D9S168 alterations were frequent in high-stage tumors. Seventy-eight patients who had ccRCC without distant metastasis at the time of surgery were followed for a median of 31.7 months. Overall survival and disease-free survival were poorer for patients with D9S168 alteration than for those without alteration (P < .001 for each; log-rank test). Cox regression analysis indicated that D9S168 alteration was associated independently with cancer-related death (P = .010). The D9S168 alteration, which was located at the 5'-untranslated region of a gene that encodes protein tyrosine phosphatase (PTP) receptor delta (PTPRD), was associated significantly with low expression of PTPRD at the messenger RNA level (P = .001). Immunohistochemistry revealed that the expression of PTPRD was strong in normal kidney proximal tubular epithelial cells, from which ccRCC originated, and was greatly down-regulated in ccRCC (P < .001; Wilcoxon rank-sum test). CONCLUSIONS: D9S168 microsatellite alteration in tumors predicted a poor prognosis for patients with ccRCC after curative nephrectomy. The authors concluded that PTPRD is a putative tumor suppressor in ccRCC and has therapeutic potential.