Carboxypeptidase E is a prognostic biomarker co-expressed with osteoblastic genes in osteosarcoma.

Osteosarcoma (OS) is a rare primary malignant bone tumor in adolescents and children with a poor prognosis. The identification of prognostic genes lags far behind advancements in treatment. In this study, we identified differential genes using mRNA microarray analysis of five paired OS tissues. Hub genes, gene set enrichment analysis, and pathway analysis were performed to gain insight into the pathway alterations of OS. Prognostic genes were screened using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, then overlapped with the differential gene dataset. The carboxypeptidase E (CPE) gene, found to be an independent risk factor, was further validated using RT-PCR and Gene Expression Omnibus (GEO) datasets. Additionally, we explored the specific expression of CPE in OS tissues by reanalyzing single-cell genomics. Interestingly, CPE was found to be co-expressed with osteoblast lineage cell clusters that expressed RUNX2, SP7, SPP1, and IBSP marker genes in OS. These results suggest that CPE could serve as a prognostic factor in osteoblastic OS and should be further investigated as a potential therapeutic target.

Development, In-Vitro Characterization and In-Vivo Osteoinductive Efficacy of a Novel Biomimetically-Precipitated Nanocrystalline Calcium Phosphate With Internally-Incorporated Bone Morphogenetic Protein-2.

The repair of large-volume bone defects (LVBDs) remains a great challenge in the fields of orthopedics and maxillofacial surgery. Most clinically available bone-defect-filling materials lack proper degradability and efficient osteoinductivity. In this study, we synthesized a novel biomimetically-precipitated nanocrystalline calcium phosphate (BpNcCaP) with internally incorporated bone morphogenetic protein-2 (BpNcCaP + BMP-2) with an aim to develop properly degradable and highly osteoinductive granules to repair LVBDs. We first characterized the physicochemical properties of the granules with different incorporation amounts of BMP-2 using scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. We evaluated the cytotoxicity and cytocompatibility of BpNcCaP by assessing the viability and adhesion of MC3T3-E1 pre-osteoblasts using PrestoBlue assay, Rhodamine-Phalloidin and DAPI staining, respectively. We further assessed the in-vivo osteoinductive efficacy in a subcutaneous bone induction model in rats. In-vitro characterization data showed that the BpNcCaP + BMP-2 granules were comprised of hexagonal hydroxyapatite with an average crystallite size ranging from 19.7 to 25.1 nm and a grain size at 84.13 ± 28.46 nm. The vickers hardness of BpNcCaP was 32.50 ± 3.58 HV 0.025. BpNcCaP showed no obvious cytotoxicity and was favorable for the adhesion of pre-osteoblasts. BMP-2 incorporation rate could be as high as 65.04 ± 6.01%. In-vivo histomorphometric analysis showed that the volume of new bone induced by BpNcCaP exhibited a BMP-2 amount-dependent increasing manner. The BpNcCaP+50 µg BMP-2 exhibited significantly more degradation and fewer foreign body giant cells in comparison with BpNcCaP. These data suggested a promising application potential of BpNcCaP + BMP-2 in repairing LVBDs.

Activity and safety of SHR3680, a novel antiandrogen, in patients with metastatic castration-resistant prostate cancer: a phase I/II trial.

BACKGROUND: Antagonizing the androgen-receptor (AR) pathway is an effective treatment strategy for patients with metastatic castration-resistant prostate cancer (CRPC). Here, we report the results of a first-in-human phase 1/2 study which assessed the safety, pharmacokinetics, and activity of SHR3680 (a novel AR antagonist) in patients with metastatic CRPC. METHODS: This phase 1/2 study enrolled patients with progressive metastatic CRPC who had not been previously treated with novel AR-targeted agents. In the phase 1 dose-escalation portion, patients received oral SHR3680 at a starting daily dose of 40 mg, which was subsequently escalated to 80 mg, 160 mg, 240 mg, 360 mg, and 480 mg per day. In phase 2 dose-expansion portion, patients were randomized to receive daily dose of 80 mg, 160 mg, or 240 mg of SHR3680. The primary endpoint in phase 1 was safety and tolerability and in phase 2 was the proportion of patients with a prostate-specific antigen (PSA) response (≥ 50% decrease of PSA level) at week 12. RESULTS: A total of 197 eligible patients were enrolled and received SHR3680 treatment, including 18 patients in phase 1 and 179 patients in phase 2. No dose-limiting toxicities were reported and the maximum tolerated dose was not reached. Treatment-related adverse events (TRAEs) occurred in 116 (58.9%) patients, with the most common one being proteinuria (13.7%). TRAEs of grade ≥ 3 occurred in only 23 (11.7%) patients, and no treatment-related deaths occurred. Antitumor activities were evident at all doses, including PSA response at week 12 in 134 (68.0%; 95% CI, 61.0-74.5) patients, stabilized bone disease at week 12 in 174 (88.3%; 95% CI, 87.2-95.5) patients, and responses in soft tissue lesions in 21 (34.4%, 95% CI, 22.7-47.7) of 61 patients. CONCLUSION: SHR3680 was well tolerated and safe, with promising anti-tumor activity across all doses tested in patients with metastatic CRPC. The dose of 240 mg daily was recommended for further phase 3 study. TRIAL REGISTRATION: Clinical trials.gov NCT02691975; registered February 25, 2016.

Mechanical Stimulation on Mesenchymal Stem Cells and Surrounding Microenvironments in Bone Regeneration: Regulations and Applications.

Treatment of bone defects remains a challenge in the clinic. Artificial bone grafts are the most promising alternative to autologous bone grafting. However, one of the limiting factors of artificial bone grafts is the limited means of regulating stem cell differentiation during bone regeneration. As a weight-bearing organ, bone is in a continuous mechanical environment. External mechanical force, a type of biophysical stimulation, plays an essential role in bone regeneration. It is generally accepted that osteocytes are mechanosensitive cells in bone. However, recent studies have shown that mesenchymal stem cells (MSCs) can also respond to mechanical signals. This article reviews the mechanotransduction mechanisms of MSCs, the regulation of mechanical stimulation on microenvironments surrounding MSCs by modulating the immune response, angiogenesis and osteogenesis, and the application of mechanical stimulation of MSCs in bone regeneration. The review provides a deep and extensive understanding of mechanical stimulation mechanisms, and prospects feasible designs of biomaterials for bone regeneration and the potential clinical applications of mechanical stimulation.

Correction: Anti-osteosarcoma effect of hydroxyapatite nanoparticles both in vitro and in vivo by downregulating the FAK/PI3K/Akt signaling pathway.

Correction for 'Anti-osteosarcoma effect of hydroxyapatite nanoparticles both in vitro and in vivo by downregulating the FAK/PI3K/Akt signaling pathway' by Renxian Wang et al., Biomater. Sci., 2020, 8, 4426-4437, DOI: 10.1039/D0BM00898B.

Analysis of Immune Gene Expression Subtypes Reveals Osteosarcoma Immune Heterogeneity.

BACKGROUND: Osteosarcoma (OS) patients have a poor response to immunotherapy due to the sheer complexity of the immune system and the nuances of the tumor-immune microenvironment. Methodology. To gain insights into the immune heterogeneity of OS, we identified robust clusters of patients based on the immune gene expression profiles of OS patients in the TARGET database and assessed their reproducibility in an independent cohort collected from the GEO database. The association of comprehensive molecular characterization with reproducible immune subtypes was accessed with ANOVA. Furthermore, we visualized the distribution of individual patients in a tree structure by the graph structure learning-based dimensionality reduction algorithm. RESULTS: We found that 87 OS samples can be divided into 5 immune subtypes, and each of them was associated with distinct clinical outcomes. The immune subtypes also demonstrated widely different patterns in tumor genetic aberrations, tumor-infiltrating, immune cell composition, and cytokine profiles. The immune landscape of OS uncovered the significant intracluster heterogeneity within each subtype and depicted a continuous immune spectrum across patients. CONCLUSION: The established five immune subtypes in our study suggested immune heterogeneity in OS patients and may provide optimal individual immunotherapy for patients exhibiting OS.

Building Osteogenic Microenvironments With Strontium-Substituted Calcium Phosphate Ceramics.

Bioceramics have experienced great development over the past 50 years. Modern bioceramics are designed to integrate bioactive ions within ceramic granules to trigger living tissue regeneration. Preclinical and clinical studies have shown that strontium is a safe and effective divalent metal ion for preventing osteoporosis, which has led to its incorporation in calcium phosphate-based ceramics. The local release of strontium ions during degradation results in moderate concentrations that trigger osteogenesis with few systemic side effects. Moreover, strontium has been proven to generate a favorable immune environment and promote early angiogenesis at the implantation site. Herein, the important aspects of strontium-enriched calcium phosphate bioceramics (Sr-CaPs), and how Sr-CaPs affect the osteogenic microenvironment, are described.

Anti-osteosarcoma effect of hydroxyapatite nanoparticles both in vitro and in vivo by downregulating the FAK/PI3K/Akt signaling pathway.

Numerous studies have reported that hydroxyapatite nanoparticles (nano-HAPs) can inhibit the proliferation of a variety of tumor cells and this effect is different in different carcinoma cells. However, the effect of nano-HAPs on osteosarcoma cell proliferation has not been well understood thus far. In this study, we first showed that our synthesized nano-HAPs reduced cell viability and inhibited migration and invasion of OS-732 cells in a concentration-dependent manner. Using a BALB/c nude mouse tumor model, we demonstrated that nano-HAPs could effectively suppress tumor growth in vivo. We also performed RNA-seq analysis to investigate the underlying mechanism of these effects and discovered that treatment of OS-732 cells with nano-HAPs significantly downregulated the FAK/PI3K/Akt signaling pathway. Collectively, our study suggests that treatment with nano-HAPs can inhibit osteosarcoma cell growth, migration and invasion in vitro and suppress osteosarcoma in vivo.

Therapeutic Potential of Circular RNAs in Osteosarcoma.

Osteosarcoma is the most common malignant bone tumor in children and adolescents. Multiagent chemotherapy, together with surgical removal of all detectable lesions, has improved the long-term survival rate to 65-70% in patients with localized osteosarcoma and to 25-30% in patients with metastatic osteosarcoma since the 1970s. However, the conventional strategy has not improved in recent decades. With accumulating knowledge of the natural circular RNA (circRNA) pathogenesis of osteosarcoma, the diagnostic and therapeutic potential of some circRNAs has been explored. Meanwhile, artificial circular RNAs have been designed as onco-microRNA inhibitors to exert antitumor functions. Therefore, natural and artificial circular RNAs, like other RNA counterparts, are attractive new classes of therapeutic molecules for the treatment of osteosarcoma. This review summarizes the latest progress in the relationship between circRNAs and the malignant phenotype of osteosarcoma and sheds light on the therapeutic potential of the two types of circular RNA in the clinic.

A polyethylenimine/salicylaldehyde modified cellulose Schiff base for selective and sensitive Fe3+ detection.

We describe a new solid-state colorimetric sensor synthesized by micro-crystalline cellulose (MCC) in the presence of polyethylenimine (PEI) and salicylaldehyde (SA) via an oxidation process and two successive Schiff base reactions. The formation of the Fe3+ complex led to color change detectable by eye, as well as an absorption peak at 501 nm causing fluorescence quenching. The signal was linear with the concentration ranging from 4 to 20 ppm; the detection limit is 0.01 ppm, making this a sensitivity and reliable monitoring platform for Fe3+ detection. Orbital electron distribution and computational studies were also carried out using density functional theory (DFT) to better supplement the sensor's detection performance. Finally, the sensing mechanism is discussed in detail.

Impact of different color fiber sleeves on beam hazards of 532-nm laser and vaporization efficiency.

The 532-nm laser has become increasingly popular for the treatment of urologic diseases. However, laser beam will pose significant hazards for the health of surgeons. In order to reduce beam hazards during surgery, we compared the beam hazards of laser fiber with black sleeves to the traditional fiber with transparent sleeves, and the vaporization efficiency. A total of 18 porcine kidney specimens were vaporized in normal saline at a room temperature under 532-nm laser delivered through a 760-µm core diameter side firing fiber. Two groups were divided according to the color of fiber sleeves: the transparent and the black. Each group was then divided into another three subgroups by laser power: the 80 W group, the 120 W group, and the 160 W group. The beam hazard was evaluated by light intensity measured in a sector area at a distance of 0 m, 0.5 m, and 1 m from the irradiation center. The vaporization efficiency was measured by the vaporization groove depth under the working power of 80 W, 120 W, and 160 W with a working distance of 5 mm and irradiation time of 10 s. The light intensity measured in the black fiber sleeve group is significantly lower than that in the transparent one (P < 0.01), regardless of the measuring distance (0 m, 0.5 m, and 1.0 m) and laser power (80 W, 120 W, and 160 W). No statistical difference was found on the vaporization efficiency between the groups protected by fiber sleeves of different colors (transparent/black, p > 0.05). Compared to the traditional transparent fiber sleeves, more beam hazards will be reduced in the operative region with the protection of black fiber sleeves, especially those from the irradiation center. The vaporization efficiency is not affected by the color of fiber sleeves. Such findings may offer a completely new idea for the protection of surgeons in surgeries with 532-nm lasers.

Photoselective Vaporesection of the Prostate via an End-firing Lithium Triborate Crystal Laser.

The occurrence of lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) is a common problem with a high incidence in the aging male population. Although it is not a life-threatening disease, BPH causes problems that seriously impact the quality of life. Here, we introduce a new technique called photoselective vaporesection of the prostate (PVRP) in treating BPH, which can be seen as a variation of photoselective vaporization of the prostate (PVP). This procedure presents several advantages compared to the PVP technique including less laser energy loss, less intraoperative complications as well as more tissue resection rate.

A comparative study of Gaussian and non-Gaussian diffusion models for differential diagnosis of prostate cancer with in-bore transrectal MR-guided biopsy as a pathological reference.

Background Although several studies have been reported on evaluating the performance of Gaussian and different non-Gaussian diffusion models on prostate cancer, few studies have been reported on the comparison of different models on differential diagnosis for prostate cancer. Purpose To compare the utility of various metrics derived from monoexponential model (MEM), biexponential model (BEM), stretched-exponential model (SEM) based diffusion-weighted imaging (DWI) and diffusion kurtosis imaging (DKI) in the differential diagnosis of prostate cancer. Material and Methods Thirty-three patients underwent magnetic resonance imaging (MRI) examination. Multi-b value and multi-direction DWIs were performed. In-bore MR-guided biopsy was performed. Apparent diffusion coefficient (ADC), pure molecular diffusion (ADCslow), pseudo-diffusion coefficient (ADCfast), perfusion fraction (f), water molecular diffusion heterogeneity index (α), distributed diffusion coefficient (DDC), non-Gaussian diffusion coefficient (MD), and mean kurtosis (MK) values were calculated and compared between cancerous and non-cancerous groups. Receiver operating characteristic (ROC) analysis was performed for all parameters and models. Results ADC, ADCslow, DDC, and MD values were significantly lower while MK value was significantly higher in prostate cancer than those of prostatitis and benign prostatic hyperplasia. ADC, ADCslow, DDC, MD, and MK could discriminate between tumor and non-tumorous lesions (area under the curve, 0.856, 0.835, 0.866, 0.918, and 0.937, respectively). MK was superior to ADC in the discrimination of prostate cancer. DKI was superior to MEM in the discrimination of prostate cancer. Conclusions Parameters derived from both Gaussian and non-Gaussian models could characterize prostate cancer. DKI may be advantageous than DWI for detection of prostate cancer.

Triptorelin relieves lower urinary tract symptoms in Chinese advanced prostate cancer patients: a multicenter, non-interventional, prospective study.

BACKGROUND: Although triptorelin is increasingly used in China for biochemical castration, its effects on primary prostate cancer symptoms remain unclear. This study aimed to assess the prevalence of lower urinary tract symptoms (LUTS) in Chinese prostate cancer patients and the effectiveness of triptorelin on LUTS. METHODS: In this 48-week multicenter, non-interventional, prospective study, we enrolled patients with locally advanced or metastatic prostate cancer. Patients received triptorelin (15 mg) intramuscularly at baseline and at weeks 12, 24, and 36 with symptom assessment using the International Prostate Symptoms Score (IPSS). The primary endpoints were the prevalence of LUTS at baseline per IPSS categories and the percentage of patients with moderate to severe LUTS (IPSS > 7) at baseline, having at least a 3-point reduction of IPSS score at week 48. RESULTS: A total of 398 patients were included; 211 (53.0%) and 160 (40.2%) among them had severe and moderate LUTS, respectively. Of the patients with IPSS scores available at baseline and at week 48 (n = 213), 81.2% achieved a reduction in IPSS of at least 3 points. Of the patients with moderate to severe LUTS at baseline and IPSS scores available at baseline and at week 48 (n = 194), 86.6% achieved a total IPSS reduction of at least 3 points. CONCLUSIONS: The vast majority of Chinese patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin as part of their standard treatment have severe or moderate LUTS. Triptorelin therapy resulted in sustained improvement of LUTS in these patients.

KIT performed as a driver gene candidate affecting the survival status of patients with stomach adenocarcinoma.

Stomach adenocarcinoma is estimated to cause 10,000 deaths in the US in 2016 and is the third most deadly cancer in China. We aim to identify the proteins and the genes that have impact on the prognosis of patients with stomach adenocarcinoma. Data of patients with stomach adenocarcinoma were retrieved from The Cancer Genome Atlas (TCGA). Proteins whose expression levels were highly correlated with survival status of patients were figured out. The expression levels of their mRNAs and their roles in the pathway were used to determine the driver gene candidates. The effects of mutations on the genes encoding KIT on mRNA expressions were carried. Ten antibodies were figured out to have significant correlation with stomach cancer prognosis. The coefficients of COXPH models matches their roles in the previous studies. The expression levels of mRNAs versus proteins suggested that KIT might act as a driver gene, which was also the central in the pathway of other selected proteins. The missense mutations on the gene encoding KIT led to the low expression of its mRNAs and there were much fewer nonsense mutations compared with other genes. It suggested that the important role of KIT as an oncogene in the progression of cancer, as well as a tyrosine-protein kinase during the normal activity. Ten antibodies, corresponding to fifteen proteins, were highly correlated with patients' survival time, within which KIT played a critical roles. It suggested that KIT might be used as biomarker or as target of cancer therapies.

Photoselective Vaporesection of the Prostate with an End-firing Lithium Triborate Crystal Laser.

BACKGROUND: Photoselective vaporization of the prostate is a technique that is widely used for the treatment of benign prostatic hyperplasia (BPH) and has pronounced advantages compared to the traditional transurethral resection of the prostate. Following the recent introduction of end-firing lithium triborate lasers, we have created a new technique called photoselective vaporesection of the prostate (PVRP). This study described our initial experience using the PVRP technique for the treatment of BPH. METHODS: This prospective study included a total of 35 patients with BPH who underwent PVRP from August 2013 to July 2014. The chief clinical parameters were obtained and evaluated during the perioperative period and follow-up, including the International Prostate Symptom Score (IPSS), quality of life (QoL) score, maximum urinary flow rate, and prostate volume. All variables were evaluated for statistically significant differences compared to baseline values using the analysis of variance. RESULTS: The mean subgroup IPSS and QoL scores significantly improved during follow-up; the respective decreases in IPSS storage score, IPSS voiding score, IPSS nocturia score, and QoL score were 75.3%, 83.6%, 51.4%, and 71.7%, respectively (all P < 0.001 compared with baseline). Three patients were diagnosed with prostate cancer based on postoperative pathological examinations. There were no serious perioperative complications. CONCLUSION: The PVRP technique demonstrates satisfactory short-term clinical outcomes and perioperative safety in the treatment of BPH.

Results of a randomized, double-blind, active-controlled clinical trial with propiverine extended release 30 mg in patients with overactive bladder.

OBJECTIVE: To compare the efficacy and safety of the 30 mg extended release (ER) formulation of propiverine hydrochloride with the 4 mg ER formulation of tolterodine tartrate in patients with overactive bladder (OAB) in a non-inferiority trial. PATIENTS AND METHODS: Eligible patients, aged 18-75 years and with symptoms of OAB, were enrolled in this multicentre, randomized, double-blind, parallel-group, active-controlled study. After a 2-week screening period, patients were randomized at a 1:1 ratio to receive either propiverine ER 30 mg or tolterodine ER 4 mg daily during the 8-week treatment period. Efficacy was assessed using a 3-day voiding diary and patient's self-reported assessment of treatment effect. Safety assessment included recording of adverse events, laboratory test results, measurement of post-void residual urine and electrocardiograms. RESULTS: A total of 324 patients (244 female and 80 male) were included in the study. Both active treatments improved the variables included in the voiding diary and in the patient's self-reported assessment. The change from baseline in the number of voidings per 24 h was significantly greater in the propiverine ER 30 mg group compared with the tolterodine ER 4 mg group after 8 weeks of treatment (full analysis set [FAS] -4.6 ± 4.1 vs -3.8 ± 5.1; P = 0.005). Significant improvements were also observed for the change of urgency incontinence episodes after 2 weeks (P = 0.026) and 8 weeks (P = 0.028) of treatment when comparing propiverine ER 30 mg with tolterodine ER 4 mg. Both treatments were well tolerated, with a similar frequency of adverse drug reactions in both the propiverine ER 30 mg and tolterodine ER 4 mg groups (FAS 40.7 vs 39.5%; P = 0.8). More patients treated with tolterodine ER 4 mg discontinued the treatment because of adverse drug reactions compared with propiverine ER 30 mg (7.4 vs 3.1%). CONCLUSIONS: Propiverine ER 30 mg was confirmed to be an effective and well-tolerated treatment option for patients with OAB symptoms. This first head-to-head study showed non-inferiority of propiverine ER 30 mg compared with tolterodine ER 4 mg.

Evaluation of the Prostate Imaging Reporting and Data System for Magnetic Resonance Imaging Diagnosis of Prostate Cancer in Patients with Prostate-specific Antigen <20 ng/ml.

BACKGROUND: The European Society of Urogenital Radiology has built the Prostate Imaging Reporting and Data System (PI-RADS) for standardizing the diagnosis of prostate cancer (PCa). This study evaluated the PI-RADS diagnosis method in patients with prostate-specific antigen (PSA) <20 ng/ml. METHODS: A total of 133 patients with PSA <20 ng/ml were prospectively recruited. T2-weighted (T2WI) and diffusion-weighted (DWI) magnetic resonance images of the prostate were acquired before a 12-core transrectal prostate biopsy. Each patient's peripheral zone was divided into six regions on the images; each region corresponded to two of the 12 biopsy cores. T2WI, DWI, and T2WI + DWI scores were computed according to PI-RADS. The diagnostic accuracy of the PI-RADS score was evaluated using histopathology of prostate biopsies as the reference standard. RESULTS: PCa was histologically diagnosed in 169 (21.2%) regions. Increased PI-RADS score correlated positively with increased cancer detection rate. The cancer detection rate for scores 1 to 5 was 2.8%, 15.0%, 34.6%, 52.6%, and 88.9%, respectively, using T2WI and 12.0%, 20.2%, 48.0%, 85.7%, and 93.3%, respectively, using DWI. For T2WI + DWI, the cancer detection rate was 1.5% (score 2), 13.5% (scores 3-4), 41.3% (scores 5-6), 75.9% (scores 7-8), and 92.3% (scores 9-10). The area under the curve for cancer detection was 0.700 (T2WI), 0.735 (DWI) and 0.749 (T2WI + DWI). The sensitivity and specificity were 53.8% and 89.2%, respectively, when using scores 5-6 as the cutoff value for T2WI + DWI. CONCLUSIONS: The PI-RADS score correlates with the PCa detection rate in patients with PSA <20 ng/ml. The summed score of T2WI + DWI has the highest accuracy in detection of PCa. However, the sensitivity should be further improved.

Diagnostic Yield and Complications Using a 20 Gauge Prostate Biopsy Needle versus a Standard 18 Gauge Needle: A Randomized Controlled Study.

PURPOSE: To compare and evaluate whether a 20 gauge (20G) biopsy needle maintains a similar detection rate as that of the commonly used 18G needle for transrectal ultrasound-guided prostate biopsy (TRUSPB) aimed at assessing prostate cancer (PCa) and decreasing pain and complications. MATERIALS AND METHODS: A total of 122 cases with indications of PCa were randomly allocated into two groups for this randomized controlled study. TRUSPB was performed randomly using either an 18G or 20G needle for core biopsies (62 cases with 18G and 60 cases with 20G). Detection rate, pain, and complications were assessed after the procedure. RESULTS: The cancer detection rate in the 18G group (40.3%) did not differ from that in the 20G group (35.0%). However, the number of patients with pain was significantly lower in 20G group (P < 0.05). The number of patients with self-limiting hematuria decreased in both groups after the biopsy procedure (18G: 38 cases; 20G: 16 cases; P < .0001). Hematochezia occurred in 11 cases (9 cases [14.5%] in the 18G group; 2 cases [3.4%] in the 20G group). The number of patients with infection, dysuria, and urinary retention tended to be lower in 20G group. CONCLUSION: Use of a 20G needle for TRUSPB yielded a comparable cancer detection rate to that of an 18G needle and led to less local injury, pain, and complications. A larger and more sensitive study is needed to verify our results.

Prophylactic intravesical chemotherapy decreases bladder tumor recurrence after nephroureterectomy for primary upper tract urothelial carcinoma: A systematic review and meta-analysis.

PURPOSE: A high incidence of bladder tumor (BT) occurs after radical nephroureterectomy (NU) for primary upper tract urothelial carcinoma (UTUC). Although some studies have shown that prophylactic intravesical chemotherapy could prevent BT recurrence, it has not become standard practice at this stage. The purpose of this study was to evaluate the effect of intravesical instillation chemotherapy in preventing BT recurrence in patients with primary UTUC after nephroureterectomy. METHODS: A comprehensive literature search was performed in July 2014 using the Medline, Embase, and Cochrane Library databases, as well as the China National Knowledge Infrastructure and Wanfang Data. All clinical trials compared the effect of prophylactic intravesical chemotherapy after radical NU for primary UTUC. Analysis was performed using the Stata 12.0 SE software. RESULTS: Eight trials were analyzed with a total of 979 patients including 521 patients receiving intravesical chemotherapy instillation and 458 without instillation. The BT incidence rate was 125 out of 521 patients (24.0%) with intravesical instillation chemotherapy after NU, and 169 out of 458 patients (36.9%) without intravesical chemotherapy after NU. Compared with those who didn't receive instillation, the pooled odds ratio (OR) of BT recurrence was 0.45 (95% confidence interval/CI 0.34-0.61, p<0.0001) in instillation patients. In the sub-analyses, the OR of single instillation was similar to repeated instillations (0.48 and 0.42). The OR of beginning the first instillation within 24 hrs, 48 hrs and 2 weeks was 0.34, 0.48 and 0.46, respectively. CONCLUSIONS: This systematic review demonstrates that prophylactic intravesical instillation chemotherapy can prevent BT recurrence in primary UTUC patients after NU. It also suggests that single instillation may have a similar effect to repeated instillations. The first instillation beginning within 24 hrs seems to show lower BT recurrence than at 48 hrs or 2 weeks. However, given that some limitations exist, well-designed randomized controlled trials are needed to further evaluate these results.