Impact of Tumor Grade Distribution on Genetic Alterations in Clear Cell Renal Cell Carcinoma and Prostate Cancer.

BACKGROUND/AIM: A genomic analysis based on next-generation sequencing is important for deciding cancer treatment strategies. Cancer tissue sometimes displays intratumor heterogeneity and a pathologic specimen may contain more than two tumor grades. Although tumor grades are very important for the cancer prognosis, the impact of higher tumor grade distribution in a specimen used for a genomic analysis is unknown. PATIENTS AND METHODS: We retrospectively analyzed the data of 61 clear cell carcinoma and 46 prostate cancer patients that were diagnosed between December 2018 and August 2022 using the GeneRead Human Comprehensive Cancer Panel or SureSelect PrePool custom Tier2. Genome annotation and curation were performed using the GenomeJack software. RESULTS: Tumor mutation burden (TMB) was increased in proportion to the higher tumor grade distribution in grade 2 clear cell renal cell carcinoma (ccRCC). In PC, Grade Group 3/4 specimens that included an increased distribution of Gleason pattern 4 had more frequent gene mutations. CONCLUSION: Our results suggest the importance of selecting the maximum distribution of higher tumor grade areas to obtain results on the precise gene alterations for genomics-focused treatments.

The Efficacy and Safety of Immune Checkpoint Inhibitor and Tyrosine Kinase Inhibitor Combination Therapy for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Real-World Cohort Study.

We evaluated the efficacy and safety of combination therapy with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKI) as first-line therapy for patients diagnosed as having advanced or metastatic renal cell carcinoma (mRCC). We enrolled 51 patients to receive ICI+TKI therapy for mRCC at 9 Japanese institutions. The overall survival (OS) of the patients treated with ICI+TKI was the primary endpoint., and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Furthermore, we analyzed the clinical prognostic and predictive factors in patients with mRCC treated with ICI+TKI therapy. Seven months was the median follow-up period. The OS rates at 6, 12, and 18 months were 93.1, 82.5, and 68.8%, respectively. The median PFS for patients who received ICI+TKI was 19.0 months, ORR was 68.6%, and DCR was 88.2%. ICI+TKI-related adverse events occurred in 43 patients (84.3%) with any grade and in 22 patients (43.1%) with grade ≥3. Treatment selection with poor prognostic factors may be prudent, even though ICI+TKI is an efficacious and safe first-line treatment in patients with mRCC.

Evaluation of physical and psychological status of health care workers infected with COVID-19 during a hospital outbreak in Japan.

PURPOSE: COVID-19 causes physical and psychological impacts on health care workers (HCWs), especially when it occurs during an outbreak. As there are few reports on outcomes of HCWs infected with COVID-19 during a hospital outbreak, we investigated the physical and psychological impacts on HCWs infected with COVID-19 during an outbreak in our hospital. METHODS: During the outbreak in our hospital, 231 people were infected with COVID-19 including patients, HCWs and their families. Among them, 83 HCWs were enrolled in this study. Current quality of life (QOL) was assessed with the EuroQol-visual analogue scales (EQ-VAS), and motivation to keep on working was evaluated by a 10-point analogue scale. Physiological recovery rates including return to work (RTW) period were also analyzed. RESULTS: One nurse quit work due to anxiety regarding re-infection with COVID-19. The median period to RTW from the diagnosis was 14.0 (12.0-17.0) days. Motivation to keep on working was slightly reduced, and the EQ-VAS was 75.0 (65.0-83.6). There were no significant differences in QOL and motivation between male and female HCWs, nurses and other HCWs, treatment and non-treatment group, and supplemental and non-supplemental oxygen group. The most frequent persistent symptoms at 1,3 and 6 months after infection were anosmia followed by fatigue. CONCLUSION: Although QOL and motivation to keep on working were slightly reduced, only one HCW quit work. No severe persistent symptoms were observed, and the RTW period was relatively short.

Efficacy and Safety of Cabozantinib in Patients with Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Cohort Study.

A multicenter retrospective study was conducted to evaluate the efficacy and safety of cabozantinib in patients with advanced or metastatic renal cell carcinoma (mRCC). We enrolled 53 patients with mRCC who received cabozantinib at eight institutions in Japan. The primary endpoint was overall survival (OS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). In addition, we analyzed prognostic factors in patients with mRCC treated with cabozantinib. The median follow-up period was 8 months, and the median OS was 20.0 months. The ORR and DCR were 39.6% and 83.0%, respectively. The median PFS was 11.0 months. PFS was significantly shorter in patients previously treated with at least two tyrosine kinase inhibitors and in those with C-reactive protein (CRP) ≥ 1.27 mg/dL (p = 0.021 and p = 0.029, respectively). Adverse events of any grade and grades ≥3 occurred in 42 (79.2%) and 10 (18.9%) patients, respectively. Cabozantinib is a useful treatment option for patients with mRCC and may benefit from earlier use. In this study, CRP ≥ 1.27 mg/dL is a poor prognostic factor in patients treated with cabozantinib, and careful follow-up may be required in treating patients with high CRP.

Effectiveness and Safety of Molecular-Targeted Therapy after Nivolumab Plus Ipilimumab for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter, Retrospective Cohort Study.

This study aimed to evaluate the effectiveness and safety of molecular-targeted therapies (MTTs) after the discontinuation of nivolumab and ipilimumab (NIVO+IPI) combination therapy in patients who had been diagnosed with advanced/metastatic renal cell carcinoma as real-world outcomes. We enrolled patients treated with MTTs following initial therapy with NIVO+IPI at nine institutions in Japan. We evaluated the objective response rate (ORR) as the primary endpoint and disease control rate (DCR), best overall response, and oncological outcomes (overall survival (OS) and progression-free survival (PFS)) as the secondary endpoints. We also evaluated factors predictive of disease progression after the administration of MTTs. Patients were followed up for a median of 8 months. The ORR was 44.8%, and the DCR was 72.4%. The median OS and PFS of MTTs after NIVO+IPI were 18 months and 8 months, respectively. A total of 31% of patients experienced grade 3/4 MTT-related adverse events. The median PFS in patients with bone metastases was significantly shorter than that in those without bone metastases (4 vs. 12 months, p = 0.012). MTTs may be a useful secondary treatment option after the discontinuation of NIVO+IPI.

Derivative Chromosome 3 Loss from t(3;6)(q12;q14) Followed by Differential VHL Mutations Underlie Multifocal ccRCC.

BACKGROUND/AIM: The Von Hippel-Lindau (VHL) gene encodes a protein (pVHL) that plays an important role in proteasome degradation of hypoxia inducible factor α (HIFα) through E3 activation. Accumulation of HIFα by loss of functional pVHL promotes tumorigenesis, thus, VHL has tumor suppressor gene capability in clear cell renal cell carcinoma (ccRCC). VHL is the most frequently mutated gene in ccRCC. The complete loss of VHL is mainly achieved by loss of chromosome 3p, which has a VHL coding region in combination with mutation or hypermethylation of the remaining copy of VHL. Given the risk of constitutional chromosome 3 translocation for RCC, it is important to detect the translocation and understand the mechanism underlying the development of multifocal ccRCC. CASE REPORT: A 67-year-old female patient diagnosed with multifocal RCC underwent robot-assisted partial nephrectomy (RAPN) for three kidney tumors. A cancer gene panel test using next generation sequencing (NGS) detected differential VHL mutations (c.533T>G; p.L178R, c.465_466insTA; p.T157Ifs*3, c.343C>A; p.H115N), while VHL mutation was not detected in peripheral blood DNA. A tendency toward copy number loss of genes on der(3) was also detected in all tumors, but not in the germline one. A karyotype analysis revealed a germline translocation between 3 and 6, t(3;6)(q12;q14). CONCLUSION: Chromosome 3 translocation and loss of derivative chromosome containing 3p and subsequent somatic differential VHL mutations in this case strongly support the previously proposed three-step model to explain the development of familial conventional ccRCC.

Clinical Lymph Node Involvement as a Predictor for Cancer-Specific Survival in Patients with Penile Squamous Cell Cancer.

We aimed to identify prognostic predictive factors of patients with penile squamous cell carcinoma (PSCC). This retrospective study reviewed the clinical and pathological data of patients with PSCC at 10 institutions in Japan between January 2008 and December 2019. The primary endpoint was cancer-specific survival (CSS). We also identified useful predictive factors for CSS in patients with PSCC. In total, 64 patients with PSCC were enrolled. At the end of the follow-up period, 15 patients (23.4%) died owing to PSCC and six (9.4%) died owing to other causes. The 2- and 3-year CSS rates were 78.9% and 76.6%, respectively. Using the Kaplan−Meier method, the Eastern Cooperative Oncology Group performance status 0, serum albumin levels ≥4.2 g/dL, hemoglobin levels ≥13.2 g/dL, C-reactive protein levels <0.21 mg/dL, clinical T stage ≤2, clinically negative lymph node (LN) status, and tumor size <30 mm were associated with a significantly better CSS. In the multivariate analysis, the clinically positive LN status was a significant predictive factor for CSS in patients with PSCC. Further prospective large-scale and long-term studies are required to validate our findings.

[A Case of Metastasis of Gastric Cancer to the Bladder].

A 62-year-old woman was diagnosed with peritoneal dissemination of gastric cancer and was treated with anticancer drugs. Eleven months after the start of the treatment, follow-up computed tomography newly showed thickening of the bladder wall and left hydronephrosis even though the chemotherapy reduced peritoneal dissemination. Therefore, she was referred to our hospital for further evaluation. Cystoscopy and magnetic resonance imaging showed the tumor arising from the bladder neck to trigone. A few days later, she was admitted to our hospital because of bladder tamponade. Transurethral coagulation was carried out, and we resected part of the bladder tumor for pathological examination at the same time. As the pathological features of the bladder tumor were similar to those of the primary stomach cancer and peritoneal dissemination, the diagnosis of the bladder tumor was metastatic gastric adenocarcinoma. She died three months after visiting our hospital.

Utility of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Systemic Immune Inflammation Index as Prognostic, Predictive Biomarkers in Patients with Metastatic Renal Cell Carcinoma Treated with Nivolumab and Ipilimumab.

The aim of this study was to assess the utility of neutrophil-to-lymphocyte ratio (NLR), plate-let-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) as predictive biomarkers with oncological outcomes for metastatic renal cell carcinoma (mRCC) patients treated with nivolumab and ipilimumab (NIVO + IPI). We conducted a retrospective multicenter cohort study assessing patients with mRCC treated with NIVO + IPI at eight institutions in Japan. In this study, the follow-up period was median 14 months. The 1-year overall- and progression-free survival (PFS) rates were 89.1% and 63.1, respectively. The objective response rate (ORR) and disease control rate (DCR) were 41.9% and 81.4%, respectively. The 1-year PFS rates were 85.7% and 49.1% for NLR ≤ 2.8 and >2.8, respectively (p = 0.005), and 75.5% and 49.7% for PLR ≤ 215.6 and >215.6, respectively (p = 0.034). Regarding SII, the 1-year PFS rates were 90.0% and 54.8% when SII was ≤561.7 and >561.7, respectively (p = 0.023). Therefore, NLR, PLR, and SII levels in mRCC patients treated with NIVO + IPI may be useful in predicting oncological outcomes.

Efficacy and Safety of Nivolumab and Ipilimumab for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Cohort Study.

We conducted a multicenter, retrospective study to evaluate the efficacy and safety of combination nivolumab plus ipilimumab (NIVO+IPI) in 35 patients with advanced or metastatic renal cell carcinoma (mRCC). In this study, we focused on patients who received NIVO+IPI and were stratified into intermediate- or poor-risk disease according to the International Metastatic Renal Cell Carcinoma Database Consortium model at five institutions in Japan. The primary endpoint was overall survival (OS). Secondary endpoints were disease control rate (DCR), best overall response (BOR), objective response rate (ORR), and progression-free survival (PFS). In addition, we evaluated the role of inflammatory cell ratios, namely neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as predictive biomarkers in patients with mRCC. The median follow-up period was 1 year, and the 1-year OS rate was 95.8%. The ORR and DCR were 34.3% and 80.0%, respectively. According to BOR, four patients (11.4%) achieved complete response. According to NLR stratification, the 1-year PFS rates were 82.6% and 23.7% when the NLR was ≤4.6 and >4.6, respectively (p = 0.04). Based on PLR stratification, the 1-year PFS rates were 81.7% and 34.3% when the PLR was ≤188.1 and >188.1, respectively (p = 0.033). Although 71.4% of the patients experienced treatment-related adverse events (TRAEs) with NIVO+IPI, only four patients discontinued NIVO+IPI due to grade 3/4 TRAEs. Patients treated with NIVO+IPI as a first-line therapy for advanced or mRCC achieved relatively better oncological outcomes. Therefore, NIVO+IPI may have potential advantages and may lead to a treatment effect compared to those receiving targeted therapies. In addition, PLR >188.1 may be a useful predictive marker for mRCC patients who received NIVO+IPI.

Comparison of plant Cd accumulation from a Cd-contaminated soil amended with biochar produced from various feedstocks.

The bioavailability of cadmium (Cd) in agricultural soils is a significant health concern due to the potential risk of human exposure via foods grown in Cd-contaminated fields. Biochar has been known to have a highly porous structure and high pH, as well as containing various functional groups; as such, it can immobilize heavy metals. Although it has found that biochar amendment in Cd-contaminated agricultural soils could be effective in reducing Cd bioavailability in previous studies, differences in plant Cd accumulation from Cd-contaminated soils amended with biochars produced from various types of biomass have not been fully discussed yet; we aimed to address this shortcoming in the present work. The soil investigated was an acid soil (pH 5.1) and had an elevated concentration of Cd (total Cd: 3.3 mg kg-DW-1). Six kinds of biochar were produced, i.e., from woodchips (Japanese cedar [CE] and Japanese cypress [CY]), moso bamboo (MB), rice husk (RH), poultry manure (PM), and wastewater sludge (WS), at a pyrolysis temperature of 600 °C. Biochars were incorporated into the Cd-contaminated soil at 3% (w/w) and pot experiments using Brassica rapa var. perviridis were conducted for 28 days in a growth chamber. The Cd concentrations in the above-ground portion of the plants were significantly decreased as a result of the incorporation of all biochars compared to the unamended soil, with reduction ratios following the order PM (78%) > > WS (31%) ≈ RH (29%) ≈ MB (28%) ≈ CY (26%) > CE (19%). Among all biochar-amended soils, soil pH and shoot biomass were highest for those amended with PM-derived biochar. These results suggest that in Cd-contaminated soils, PM-derived biochar may offer significant potential in reducing plant Cd accumulation due to the immobilization of soil Cd and an effect of dilution resulting from enhanced plant shoot biomass.

The Preliminary Study of Water-Retention Related Properties of Biochar Produced from Various Feedstock at Different Pyrolysis Temperatures.

Physicochemical properties of biochar, which are used as a soil amendment material in agricultural fields, are different depending on biomass feedstock and pyrolysis processes. In this study, we evaluated the influence of feedstock type and pyrolysis temperature on the water-retention related properties of biochar. Wood-chips [cedar (CE) and cypress (CY)]; moso bamboo (MB); rice husk (RH); sugarcane bagasse (SB); poultry manure (PM) and agricultural wastewater sludge (WS) were each pyrolysed at 400, 600 and 800 °C with a retention time of two hours. Scanning electron microscopy micrographs (SEM), hydrophobicity indices, pore-size distribution measured by mercury-intrusion porosimetry, water-retention curves (WRCs) and plant-available water capacities (AWCs) of the biochars were measured to evaluate their potentials as soil-amendment materials for improving soils' water-retention. As the pyrolysis temperature was increased, the hydrophobicity index decreased. On the other hand, pyrolysis temperature did not affect the distribution of micrometre-range pores, which are useful for plant-available water, of biochars. The AWCs of the biochars formed from CE, CY and SB were greater than those produced from other feedstocks, at 600 and 800 °C. Therefore, we can suggest that the biochars derived from wood-chips (CE and CY) and SB have greater potential for enhancing soils' water-retention.

Urinary exosome as a potential biomarker for urinary tract infection.

Unlike urinary tract infection (UTI), asymptomatic bacteriuria (ABU) should not be treated, with some exceptions such as pregnant women and patients who will undergo traumatic urologic interventions. However, there has been no clinically available marker for their differential diagnosis. Exosomes or small extracellular vesicles carry proteins contained in cells from which they are derived, thus having the potential as a biomarker of several diseases. On the basis of the hypothesis that the molecular signature of exosomes in urine may differ between UTI and ABU patients, we examined if urinary exosomes could serve as a marker for their differential diagnosis. Exosomes were isolated by ultracentrifugation or affinity-based method from cell culture medium of monocytic THP-1 and uroepithelial SV-HUC-1 cells and human urine. Protein expression was examined by Western blot analysis, ELISA, and CLEIA. The results showed that the levels of intracellular signalling molecules Akt and ERK and transcription factor NF-κB increased in exosomes isolated from THP-1 and SV-HUC-1 cells cocultured with Escherichia coli and/or treated with lipopolysaccharide. In urinary exosomes of UTI patients, Akt significantly diminished, and an exosomal marker CD9 showed a trend to decrease after treatment with antimicrobial agents. More importantly, Akt and CD9 levels in urinary exosomes were higher in UTI patients than in ABU patients, which was also observed after correction by urine creatinine. Collectively, these results suggest that Akt and CD9 in urinary exosomes could be useful markers for differential diagnosis of UTI and ABU.

Metastatic epithelioid angiomyolipoma treated with everolimus in a patient receiving hemodialysis: A case report.

INTRODUCTION: A patient undergoing hemodialysis and being treated with everolimus for metastatic epithelioid angiomyolipoma has never been described in the literature, to our knowledge. CASE PRESENTATION: A 53-year-old woman who had undergone trans-arterial embolization for epithelioid angiomyolipoma was referred with a chief complaint about right knee pain. Hemodialysis had been started after the embolization. Needle biopsy specimens of tumors obtained from behind the right kidney and in the right femur were diagnosed as epithelioid angiomyolipoma metastases. The patient underwent treatment with everolimus and achieved a partial response after 6 months of treatment without serious adverse events. CONCLUSION: Everolimus might be effective for patients with metastatic epithelioid angiomyolipoma who are undergoing hemodialysis.

Oral administration of cernitin pollen extract (Cernilton® ) for 30 days might be useful to avoid unnecessary biopsy in prostate biopsy candidates: A preliminary study.

OBJECTIVES: To assess the effect of cernitin pollen extract on serum prostate-specific antigen level prostate biopsy candidates, and to develop an ideal protocol to avoid an unnecessary biopsy procedure. METHODS: A total of 61 patients were administrated cernitin pollen extract tablets (two tablets t.i.d.) for 30 days, and then underwent a prostate biopsy with ≥12 systematic and targeted biopsy cores obtained. Serum prostate-specific antigen levels were examined before and after administration of the pollen extract, and the change in serum prostate-specific antigen and the rate of change were analyzed in relation to negative and positive biopsy results for cancer. RESULTS: The mean change in serum prostate-specific antigen and rate of change after administration of cernitin pollen extract in all patients were -0.6 ± 1.4 ng/mL and -7.6 ± 16.1%, respectively, which were significantly different from the baseline values (P = 0.0003 and P = 0.0005, respectively). When prostate-specific antigen change values and rates were compared between patients negative and positive for cancer, a significant difference between those groups was observed (P = 0.04 and P = 0.03, respectively). CONCLUSIONS: The present study is the first to show that an ideal protocol using cernitin pollen extract has the potential to avoid an unnecessary prostate biopsy procedure in patients with elevated prostate-specific antigen, possibly caused by inflammation. Additional studies with greater numbers of participants are required to confirm our findings and develop an ideal protocol.

Organ-confined plasmacytoid urothelial carcinoma: implication of the lack of expression of the receptor tyrosine kinase MET.

Plasmacytoid urothelial carcinoma (PUC), a morphological variant of urothelial carcinoma (UC), is composed of cancer cells that resemble plasma cells, monocytes, or both, and is clinicopathologically distinguished by its aggressive, non-organ-confined features. Here, we present a case of a patient with PUC with early invasion at diagnostic transurethral resection. Histopathologically, no residual cancer or lymph node metastasis was observed by total cystectomy. The patient remains disease-free after 18 months, without undergoing adjuvant chemotherapy. Interestingly, the immunoreactivity of MET, a receptor tyrosine kinase expressed in many invasive UCs, was minimal in the cancer cells. In contrast, archival pathological, non-organ-confined PUC cells exhibited strong MET immunoreactivity. The present case may imply a role for the MET protein in the aggressive behavior of PUCs. We propose the putative usefulness of MET inhibitors for the treatment of aggressive PUCs.

Exosomes expressing carbonic anhydrase 9 promote angiogenesis.

Exosomes or microvesicles that are secreted from cells are considered to play important roles in tumor microenvironment. Carbonic anhydrase 9 (CA9), which is induced by hypoxia-inducible factor 1 (HIF1) in response to hypoxia, is overexpressed in many types of cancer including renal cell carcinoma (RCC). We examined the expression level of CA9 in several RCC cell lines and found that the basal level of CA9 was much higher in OSRC-2 cells than in Caki-1, KMRC-1 and 786-O cells. Consistent with the intracellular expression levels, CA9 was abundantly detected in exosomes isolated by ultracentrifugation from OSRC-2 cells. Density gradient centrifugation of OSRC-2 and 786-O exosomes confirmed the co-presence of CA9 with exosomal markers. Upon hypoxia and treatment with CoCl2, a hypoxia mimic agent, the CA9 level in exosomes was increased for all cell lines. In order to examine the effects of CA9 exosomes on angiogenesis, we generated stably transfected HEK293 cells expressing CA9. Immunocytochemical staining demonstrated the uptake of CA9 exosomes by human umbilical vein endothelial cells (HUVEC). In vitro angiogenesis assays using HUVEC revealed that CA9 exosomes promoted migration and tube formation. Lastly, MMP2 expression was increased by treatment with CA9 exosomes in HUVEC. Taken together, our results suggest the possibility that CA9 exosomes released from hypoxic RCC may enhance angiogenesis in microenvironment, thereby contributing to cancer progression.

Gamma-glutamyltransferase activity in exosomes as a potential marker for prostate cancer.

BACKGROUND: Exosomes or extracellular vesicles have the potential as a diagnostic marker for various diseases including cancer. In order to identify novel exosomal markers for prostate cancer (PC), we performed proteomic analysis of exosomes isolated from PC cell lines and examined the usefulness of the marker in patients. METHODS: Exosomes isolated by differential centrifugation from the culture medium of androgen-dependent LNCaP prostate cancer cell line and its sublines of partially androgen-independent C4, androgen-independent C4-2 and bone metastatic C4-2B were subjected to iTRAQ-based proteomic analysis. Exosomes were also isolated by immunocapture and separated by size exclusion chromatography and density gradient centrifugation. Protein expression was determined by Western blot analysis. GGT activity was measured using a fluorescent probe, γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG). Immunohistochemical analysis of tissues was performed using anti-GGT1 antibody. RESULTS: Among proteins upregulated in C4-2 and C4-2B cells than in LNCaP cells, we focused on gamma-glutamyltransferase 1 (GGT1), a cell-surface enzyme that regulates the catabolism of extracellular glutathione. The levels of both GGT1 large and small subunits were elevated in exosomes isolated from C4-2 and C4-2B cells by differential centrifugation and by immunocapture with anti-CD9 or -prostate-specific membrane antigen (PSMA) antibody. In cell lysates and exosomes, GGT1 expression correlated with GGT activity. Size exclusion chromatography of human serum demonstrated the presence of GGT activity and GGT1 subunits in fractions positive for CD9. Density gradient centrifugation revealed the co-presence of GGT1 subunits with CD9 in exosomes isolated by differential centrifugation from human serum. Since GGT activity correlated with GGT1 expression in serum exosomes isolated by differential centrifugation, we measured serum exosomal GGT activity in patients. Unexpectedly, we found that serum exosomal GGT activity was significantly higher in PC patients than in benign prostatic hyperplasia (BPH) patients. In support of this finding, immunohistochemical analysis showed increased GGT1 expression in PC tissues compared with BPH tissues. CONCLUSIONS: Our results suggest that serum exosomal GGT activity could be a useful biomarker for PC.

Enzalutamide inhibits proliferation of gemcitabine-resistant bladder cancer cells with increased androgen receptor expression.

Advanced bladder cancer is treated mainly with gemcitabine and cisplatin, but most patients eventually become resistance. Androgen receptor (AR) signaling has been implicated in bladder cancer as well as other types of cancer including prostate cancer. In this study, we investigated the expression and role of AR in gemcitabine-resistant bladder cancer cells and also the potential of enzalutamide, an AR inhibitor, as a therapeutic for the chemoresistance. First of all, we established gemcitabine-resistant T24 cells (T24GR) from T24 bladder cancer cells and performed gene expression profiling. Microarray analysis revealed upregulation of AR expression in T24GR cells compared with T24 cells. AR mRNA and protein expression was confirmed to be increased in T24GR cells, respectively, by quantitative RT-PCR and western blot analysis, which was associated with more potent AR transcriptional activity as measured by luciferase reporter assay. The copy number of AR gene in T24GR cells determined by PCR was twice as many as that of T24 cells. AR silencing by siRNA transfection resulted in inhibition of proliferation of T24GR cells. Cell culture in charcoal-stripped serum and treatment with enzalutamide inhibited growth of T24GR cells, which was accompanied by cell cycle arrest. AR transcriptional activity was found to be reduced in T24GR cells by enzalutamide treatment. Lastly, enzalutamide also inhibited cell proliferation of HTB5 bladder cancer cells that express AR and possess intrinsic resistance to gemcitabine. Our results suggest that enzalutamide may have the potential to treat patients with advanced gemcitabine-resistant bladder cancer with increased AR expression.

Postoperative infectious complications in patients undergoing holmium laser enucleation of the prostate: Risk factors and microbiological analysis.

OBJECTIVES: To examine the incidence of postoperative bacteriuria and febrile complications, and to investigate bacterial strains in the urine of patients undergoing holmium laser enucleation of the prostate. METHODS: We retrospectively analyzed 190 evaluable patients treated with holmium laser enucleation of the prostate at the Gifu University Hospital, Gifu, Japan, between September 2005 and May 2014. All patients presented with lower urinary tract symptoms as a result of benign prostatic hyperplasia. We also evaluated the causative bacteria and compared the findings with the results of preoperative urine cultures. We analyzed the relationship between the emergence of postoperative febrile complications, antibiotic prophylaxis, patient background and surgical procedure. RESULTS: The frequency of bacterial isolation in preoperative and postoperative urine cultures was 41% and 23%, respectively. Preoperatively, Enterococcus faecalis was the most frequently cultured bacteria, second was methicillin-resistant Staphylococcus epidermidis, and third was Escherichia coli. Postoperatively, Enterococcus faecalis was still the most frequently cultured bacteria, whereas the second was Escherichia coli. Risk factors for postoperative bacteriuria were evaluated. Multivariate analysis showed that the rate of postoperative bacteriuria in patients who had taken dutasteride preoperatively was significantly lower than that in the other patients. Risk factors for febrile complications could not be identified. CONCLUSIONS: The use of perioperative prophylactic antibacterial agents for holmium laser enucleation of the prostate keeps the rate of postoperative infectious complications low. Dutasteride treatment administered before surgery might reduce the risk of postoperative bacteriuria.