Bladder stone formation around polyethylene glycol after use of SpaceOAR Hydrogel.

Introduction: Radiation therapy is used as primary, adjuvant, and salvage therapy for prostate cancer. When using radiation therapy, the SpaceOAR® system is considered easy to use and useful for reducing the irradiated dose and toxicity to the rectum. Although SpaceOAR® system have been reported some adverse event including death. Case presentation: A 74-year-old male was diagnosed with prostate cancer of clinical stage cT2aN0M0 and intermediate risk by the National Comprehensive Cancer Network guidelines. We inserted the SpaceOAR® Hydrogel before performing intensity-modulated radiation therapy, as the patient had ulcerative colitis. We did not recognize any complications during or after the procedure, although magnetic resonance imaging revealed hydrogel in the bladder retrospectively. Fourteen months after the procedure, the patient was presented with macrohematuria and we found a bladder stone including hydrogel. Conclusion: We report the first case of a bladder stone after use of SpaceOAR® Hydrogel. We must be careful of taking place it.

Comparison of single- and multiple-dose cefazolin as prophylaxis for transurethral enucleation of prostate: A multicenter, prospective, randomized controlled trial by the Japanese Research Group for Urinary Tract Infection.

OBJECTIVES: To compare the optimal administration period of antimicrobial prophylaxis in patients undergoing transurethral enucleation of the prostate for benign prostatic hyperplasia. METHODS: We carried out a randomized controlled trial to compare the differences in incidence of perioperative genitourinary tract infection between single and multiple (3 days) administrations of cefazolin for transurethral enucleation of the prostate in benign prostatic hyperplasia patients without pyuria or bacteriuria between January 2015 and December 2018. RESULTS: This multicenter randomized controlled trial included 203 patients who underwent a transurethral enucleation of the prostate procedure. All received antimicrobial prophylaxis, and were randomized into those who received single-dose (n = 101) or multiple-dose (n = 102) therapy. The rate of genitourinary tract infection after transurethral enucleation of the prostate for all patients was 1.5%, whereas that in the single-dose group was 1.0% and in the multiple-dose group was 2.0%, which were not significantly different (P = 1.00). CONCLUSIONS: A single dose of antimicrobial prophylaxis as a prophylactic antibacterial drug is sufficient for patients undergoing transurethral enucleation of the prostate who do not have presurgical pyuria or bacteriuria.

Oncological impact of neoadjuvant hormonal therapy on permanent iodine-125 seed brachytherapy in patients with low- and intermediate-risk prostate cancer.

OBJECTIVES: To determine whether neoadjuvant hormonal therapy improves oncological outcomes of patients with localized prostate cancer treated with permanent brachytherapy. METHODS: Between January 2004 and November 2014, 564 patients underwent transperineal ultrasonography-guided permanent iodine-125 seed brachytherapy. We retrospectively analyzed low- or intermediate-risk prostate cancer based on the National Comprehensive Cancer Network guidelines. The clinical variables were evaluated for influence on biochemical recurrence-free survival, progression-free survival, cancer-specific survival and overall survival. RESULTS: A total of 484 patients with low-risk (259 patients) or intermediate-risk disease (225 patients) were evaluated. Of these, 188 received neoadjuvant hormonal therapy. With a median follow up of 71 months, the 5-year actuarial biochemical recurrence-free survival rates of patients who did and did not receive neoadjuvant hormonal therapy were 92.9% and 93.6%, respectively (P = 0.2843). When patients were stratified by risk group, neoadjuvant hormonal therapy did not improve biochemical recurrence-free survival outcomes in low- (P = 0.8949) or intermediate-risk (P = 0.1989) patients. The duration or type of hormonal therapy was not significant in predicting biochemical recurrence. In a multivariate analysis, Gleason score, pretreatment prostate-specific antigen, clinical T stage, and prostate dosimetry, primary Gleason score and positive core rate were significant predictive factors of biochemical recurrence-free survival, whereas neoadjuvant hormonal therapy was insignificant. Furthermore, neoadjuvant hormonal therapy did not significantly influence progression-free survival, cancer-specific survival or overall survival. CONCLUSIONS: In patients with low- or intermediate-risk disease treated with permanent prostate brachytherapy, neoadjuvant hormonal therapy does not improve oncological outcomes. Its use should be restricted to patients who require prostate volume reduction.

Synergistic effects of the immune checkpoint inhibitor CTLA-4 combined with the growth inhibitor lycorine in a mouse model of renal cell carcinoma.

Renal cell carcinoma (RCC) management has undergone a major transformation over the past decade; immune checkpoint inhibitors are currently undergoing clinical trials and show promising results. However, the effectiveness of immune checkpoint inhibitors in patients with metastatic RCC (mRCC) is still limited. Lycorine, an alkaloid extracted from plants of the Amaryllidaceae family, is touted as a potential anti-cancer drug because of its demonstrative growth inhibition capacity (induction of cell cycle arrest and inhibition of vasculogenic mimicry formation). Moreover, T cell checkpoint blockade therapy with antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA-4) has improved outcomes in cancer patients. However, the anti-tumor efficacy of combined lycorine and anti-CTLA-4 therapy remains unknown. Thus, we investigated a combination therapy of lycorine hydrochloride and anti-CTLA-4 using a murine RCC model. As a means of in vitro confirmation, we found that lycorine hydrochloride inhibited the viability of various RCC cell lines. Furthermore, luciferase-expressing Renca cells were implanted in the left kidney and the lung of BALB/c mice to develop a RCC metastatic mouse model. Lycorine hydrochloride and anti-CTLA-4 synergistically decreased tumor weight, lung metastasis, and luciferin-staining in tumor images. Importantly, the observed anti-tumor effects of this combination were dependent on significantly suppressing regulatory T cells while upregulating effector T cells; a decrease in regulatory T cells by 31.43% but an increase in effector T cells by 31.59% were observed in the combination group compared with those in the control group). We suggest that a combination of lycorine hydrochloride and anti-CTLA-4 is a viable therapeutic option for RCC patients.

Efficacy and safety of 3 day versus 7 day cefditoren pivoxil regimens for acute uncomplicated cystitis: multicentre, randomized, open-label trial.

BACKGROUND: Fluoroquinolone-non-susceptible Escherichia coli isolated from patients with acute uncomplicated cystitis are a matter of increasing concern. Cefditoren pivoxil is an oral, ß-lactamase-stable, extended-spectrum cephalosporin that is effective against fluoroquinolone-non-susceptible bacteria. OBJECTIVES: To evaluate the clinical and microbiological efficacies of cefditoren pivoxil against acute uncomplicated cystitis and to determine the optimal duration of cefditoren pivoxil treatment. METHODS: We compared 3 and 7 day regimens of cefditoren pivoxil in a multicentre, randomized, open-label study. RESULTS: A total of 104 female patients with acute uncomplicated cystitis were enrolled and randomized into 3 day (n = 51) or 7 day (n = 53) treatment groups. At first visit, 94 bacterial strains were isolated from the 104 participants of which 81.7% (85/104) were E. coli. Clinical and microbiological efficacies were evaluated 5-9 days following administration of the final dose of cefditoren pivoxil. The clinical efficacies of the 3 and 7 day groups were 90.9% (40/44) and 93.2% (41/44), respectively (P = 1.000). The microbiological efficacies of the 3 and 7 day groups were 82.5% (33/40) and 90.2% (37/41), respectively (P = 0.349). There were no adverse events due to cefditoren pivoxil treatment, with the exception of a mild allergic reaction in one patient, after which the cefditoren pivoxil was exchanged for another antimicrobial. CONCLUSIONS: Cefditoren pivoxil is safe and effective for uncomplicated cystitis, with no significant differences in clinical and microbiological efficacies between 3 and 7 day regimens.

Distribution of oral streptococci highly resistant to amoxicillin in dental plaque specimens from Japanese children and adolescents.

Oral streptococci are major pathogens of infective endocarditis. Prophylactic antibiotics are commonly given to subjects with certain kinds of heart disorders when invasive dental treatments are performed, with amoxicillin (AMPC) being widely used for this purpose. However, there is little information regarding AMPC-resistant oral streptococci. Here, a total of 344 dental plaque specimens collected from 253 healthy Japanese children, adolescents and young adults (aged 2-22 years) were diluted and streaked onto culture medium containing high-dose AMPC. The MICs for the isolated strains were evaluated using a macrodilution broth method described by the Clinical and Laboratory Standards Institute. Bacterial DNA was extracted from each strain and the entire sequences of the 16S rRNA gene were compared with those in GenBank to identify the species. The results showed that strains with AMPC MICs >16 µg ml(-1) were isolated from 18 specimens from 14 patients. Analyses of the 16S rRNA gene sequences of these strains identified them as major oral streptococcal species, including Streptococcus oralis and Streptococcus mitis. These findings indicate that oral streptococci with elevated MICs for AMPC exist in certain small populations of healthy children, and highlight the need for further studies to determine risk factors that lead to the appearance of such strains.

Long-term combination therapy of ezetimibe and acarbose for non-alcoholic fatty liver disease.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome that is closely associated with multiple factors such as obesity, hyperlipidemia, type 2 diabetes mellitus and hypertension, making it difficult to treat NAFLD effectively using any monotherapy available to date. In this study, we propose a novel combination therapy for NAFLD comprising ezetimibe (EZ), a cholesterol absorption inhibitor, and acarbose (AC), an alpha-glucosidase inhibitor. METHODS: C57BL/6J mice were divided into five treatment groups as follows: basal diet (BD), high-fat diet (HFD) only, HFD with EZ (5mg/kg/day), HFD with AC (100mg/kg/day), and HFD with both EZ and AC for 24 weeks. RESULTS: Long-term combination therapy with EZ and AC significantly reduced steatosis, inflammation and fibrosis in the liver, compared with long-term monotherapy with either drug, in an HFD-induced NAFLD mouse model; the combination therapy also significantly increased the expression of microsomal triglyceride transfer protein (MTP) and peroxisome proliferators-activated receptor-alpha1 (PPAR-alpha1) in the liver, compared with either monotherapy, which may have led to the improvement in lipid metabolic disorder seen in this model. CONCLUSIONS: Combination therapy with EZ and AC for 24 weeks improved the histopathological findings in a mouse model of NAFLD.

Chemoprevention of precursors to colon cancer by dehydroepiandrosterone (DHEA).

Although dehydroepiandrosterone (DHEA) is recognized as one of the major adrenal androgens, its precise physiological role in the human endocrine system remains to be elucidated. In particular, the effect of DHEA on carcinogenesis has not been fully characterized. We undertook this study to determine whether DHEA has a chemopreventative effect on the precursors of colon cancer in a murine model of azoxymethane (AOM)-induced aberrant crypt foci (ACF). The number of ACF was significantly decreased in mice treated with 0.4% (p < 0.001) and 0.8% DHEA (p < 0.001), but there were no significant differences between DHEA-treated and control mice in terms of the ACF size, 3-catenin expression or level of dysplasia. This is the first study of colon cancer carcinogenesis demonstrating that DHEA treatment can decrease the number of ACF without apparently modifying their malignant potential. These data strongly suggest that DHEA might be a potential chemopreventative agent against human colon cancer.

PPAR gamma ligands inhibit nitrotyrosine formation and inflammatory mediator expressions in adjuvant-induced rheumatoid arthritis mice.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor, whose activation has been linked to several physiologic pathways including those related to the regulation of insulin sensitivity. Here, we investigate effects of PPARgamma specific ligands, rosiglitazone and pioglitazone, on formation of nitrotyrosine and increased expression of inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 and intercellular adhesion molecule-1 (ICAM-1) in adjuvant-induced murine arthritis. Administration of rosiglitazone or pioglitazone (30 mg/kg, p.o.) significantly inhibited the adjuvant-induced increase in formation of nitrotyrosine and expression of iNOS on both ankle and temporomandibular joints. Rosiglitazone also inhibited the adjuvant-induced expression of M30 positive cells, as a marker of apoptosis, in the joint tissues. In addition, treatment with rosiglitazone or pioglitazone (30 microM) inhibited lipopolysaccharide plus tumor necrosis factor (TNF)-alpha-induced protein expression of iNOS, cyclooxygenase-2, ICAM-1 and nitrotyrosine formation in RAW 264 cells, a murine macrophage-like cell line. Rosiglitazone or pioglitazone inhibited increase in phosphorylated I-kappaB (pI-kappaB) expression, as an index of activation of nuclear factor (NF)-kappaB, in both joint tissues and RAW264 cells. Furthermore, in PPARgamma-transfected HEK293 cells, rosiglitazone inhibited the TNF-alpha-stimulated response using NF-kappaB-mediated transcription reporter assay. These results indicate that PPARgamma ligands may possess anti-inflammatory activity against adjuvant-induced arthritis via the inhibition of NF-kappaB pathway.