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1.  Feasibly of axitinib as first-line therapy for advanced or metastatic renal cell carcinoma: a single-institution experience in Japan 
BMC Urology  2015;15:32.
Clinical benefit of axitinib as a first line agent to treat patients with metastatic renal cell carcinoma (mRCC), or locally advanced renal cell carcinoma (RCC) have not been clearly demonstrated. The aim of this study was to evaluate the efficacy and safety of axitinib as first-line therapy in Japanese patients with locally advanced RCC or mRCC.
In this retrospective study, we focused on eighteen patients who underwent first-line therapy with axitinib between May 2012 and May 2014 at Hirosaki University. Axitinib was orally administered at a dose of 10 mg daily. Progression-free survival (PFS) was the primary endpoint, while secondary endpoints included overall response rate (ORR) and adverse events (AEs).
All patients had histologically proven clear cell RCC. The median duration of the administration of axitinib was 10.8 months. According to the response evaluation criteria for solid tumors, five patients (27.8%) achieved a partial response and nine (50%) had stable disease. The 1-year PFS rate was 84.4%, and the median PFS was 20.4 months (95% confidence interval, 17.5 – 21.7). No serious AEs were reported during the study, and there were no toxicity-related deaths.
In the current study, axitinib showed acceptable oncological outcomes and favorable safety profile as first-line therapy for locally advanced RCC or mRCC in treatment-naïve Japanese patients. Thus, first-line therapy with axitinib may provide a feasible option for treatment of advanced RCC or mRCC patients.
PMCID: PMC4417199  PMID: 25887125
Axitinib renal cell carcinoma; First-line; Vascular endothelial growth factor receptor; Advanced renal cell carcinoma; Metastatic renal cell carcinoma
2.  Tramadol for premature ejaculation: a systematic review and meta-analysis 
BMC Urology  2015;15:6.
Tramadol is a centrally acting analgesic prescribed off-label for the treatment of premature ejaculation (PE). However, tramadol may cause addiction and difficulty in breathing and the beneficial effect of tramadol in PE is yet not supported by a high level of evidence. The purpose of this study was to systematically review the evidence from randomised controlled trials (RCT) for tramadol in the management of PE.
We searched bibliographic databases including MEDLINE to August 2014 for RCTs. The primary outcome was intra-vaginal ejaculatory latency time (IELT). Methodological quality of RCTs was assessed. Between-group differences in IELT and other outcomes were pooled across RCTs in a meta-analysis. Statistical and clinical between-trial heterogeneity was assessed.
A total of eight RCTs that evaluated tramadol against a comparator were included. The majority of RCTs were of unclear methodological quality due to limited reporting. Pooled evidence (four RCTs, 721 participants), suggests that tramadol is significantly more effective than placebo at increasing IELT over eight to 12 weeks (p = 0.0007). However, a high level of statistical heterogeneity is evident (I-squared = 74%). Single RCT evidence indicates that tramadol is significantly more effective than paroxetine taken on-demand, sildenafil, lidocaine gel, or behavioural therapy on IELT in men with PE. Tramadol is associated with significantly more adverse events including: erectile dysfunction, constipation, nausea, headache, somnolence, dry mouth, dizziness, pruritus, and vomiting, than placebo or behavioural therapy over eight to 12 weeks of treatment. However, addiction problems or breathing difficulties reported by patients for PE is not assessed in the current evidence base.
Tramadol appears effective in the treatment of PE. However, these findings should be interpreted with caution given the observed levels of between-trial heterogeneity and the reporting quality of the available evidence. The variability across placebo-controlled trials in terms of the tramadol dose evaluated and the treatment duration does not permit any assessment of a safe and effective minimum daily dose. The long-term effects and side effects, including addiction potential, for men with PE have not been evaluated in the current evidence base.
Trial registration
The review is registered on PROSPERO 2013:CRD42013005289.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2490-15-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4417346  PMID: 25636495
Premature ejaculation; Tramadol; Systematic review; Meta-analysis; Efficacy; Safety
3.  Haemaphysalis longicornis Ticks as Reservoir and Vector of Severe Fever with Thrombocytopenia Syndrome Virus in China 
Emerging Infectious Diseases  2015;21(10):1770-1776.
Transstadial and transovarial virus transmission occur among ticks, and transmission to mice can occur through a tick bite.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in East Asia caused by SFTS virus (SFTSV), a newly discovered phlebovirus. The Haemaphysalis longicornis tick has been suspected to be the vector of SFTSV. To determine whether SFTSV can be transmitted among ticks, from ticks to animals, and from animals to ticks, we conducted transmission studies between developmental stages of H. longicornis ticks and between ticks and mice. Using reverse transcription PCR, we also analyzed the prevalence of SFTSV infection among H. longicornis ticks collected from vegetation in Shandong Province, China. Our results showed a low prevalence of SFTSV among collected ticks (0.2%, 8/3,300 ticks), and we showed that ticks fed on SFTSV-infected mice could acquire the virus and transstadially and transovarially transmit it to other developmental stages of ticks. Furthermore, SFTSV-infected ticks could transmit the virus to mice during feeding. Our findings indicate ticks could serve as a vector and reservoir of SFTSV.
PMCID: PMC4593435  PMID: 26402039
bunyavirus; phlebovirus; severe fever with thrombocytopenia syndrome; severe fever with thrombocytopenia syndrome virus; SFTSV; ticks; Haemaphysalis longicornis; viruses; vector-borne infections; transmission; transstadial transmission; transovarial transmission; tickborne transmission; vector; host; larvae; nymphs; adult ticks; China
4.  Using mathematical models to understand metabolism, genes, and disease 
BMC Biology  2015;13:79.
Mathematical models are a useful tool for investigating a large number of questions in metabolism, genetics, and gene–environment interactions. A model based on the underlying biology and biochemistry is a platform for in silico biological experimentation that can reveal the causal chain of events that connect variation in one quantity to variation in another. We discuss how we construct such models, how we have used them to investigate homeostatic mechanisms, gene–environment interactions, and genotype–phenotype mapping, and how they can be used in precision and personalized medicine.
PMCID: PMC4580265  PMID: 26400419
6.  The influence of finfish aquaculture on benthic fish and crustacean assemblages in Fitzgerald Bay, South Australia 
PeerJ  2015;3:e1238.
The influence of sea-cage aquaculture on wildfish assemblages has received little attention outside of Europe. Sea-cage aquaculture of finfish is a major focus in South Australia, and while the main species farmed is southern bluefin tuna (Thunnus maccoyii), there is also an important yellowtail kingfish (Seriola lalandi) industry. Yellowtail kingfish aquaculture did not appear to have any local or regional effects on demersal assemblages (primarily fish, but also some crustaceans) surveyed by baited remote underwater video (BRUV) in Fitzgerald Bay. We did, however, detect small scale spatial variations in assemblages within the bay. The type of bait used strongly influenced the assemblage recorded, with significantly greater numbers of fish attracted to deployments where sardines were used as the bait to compared to those with no bait. The pelleted feed used by the aquaculture industry was just as attractive as sardines at one site, and intermediate between sardines and no bait at the other. There was significant temporal variability in assemblages at both farm sites and one control site, while the second control site was temporally stable (over the 9 weeks of the study). Overall, the results suggested that aquaculture was having little if any impact on the abundance and assemblage structure of the demersal macrofauna in Fitzgerald Bay.
PMCID: PMC4579018  PMID: 26401452
Yellowtail kingfish; Seriola lalandi; Wildfish; Aquaculture impacts; BRUVs; Finfish aquaculture
7.  Annual trends of human brucellosis in pastoralist communities of south-western Uganda: a retrospective ten-year study 
Human brucellosis is prevalent in both rural and urban Uganda, yet most cases of the disease in humans go unnoticed and untreated because of inaccurate diagnosis, which is often due to the disease not manifesting in any symptoms. This study was undertaken to describe trends in laboratory-confirmed human brucellosis cases at three health facilities in pastoralist communities in South-western, Uganda.
Data were collected retrospectively to describe trends of brucellosis over a 10-year period (2003–2012), and supplemented with a prospective study, which was conducted from January to December 2013. Two public health facilities and a private clinic that have diagnostic laboratories were selected for these studies. Annual prevalence was calculated and linearly plotted to observe trends of the disease at the health facilities. A modified Poisson regression model was used to estimate the risk ratio (RR) and 95 % confidence intervals (CIs) to determine the association between brucellosis and independent variables using the robust error variance.
A total of 9,177 persons with suspected brucellosis were identified in the retrospective study, of which 1,318 (14.4 %) were confirmed cases. Brucellosis cases peaked during the months of April and June, as observed in nearly all of the years of the study, while the most noticeable annual increase (11–23 %) was observed from 2010 to 2012. In the prospective study, there were 610 suspected patients at two public health facilities. Of these, 194 (31.8 %) were positive for brucellosis. Respondents aged 45–60 years (RR = 0.50; CI: 0.29–0.84) and those that tested positive for typhoid (RR = 0.68; CI: 0.52–0.89) were less likely to have brucellosis.
With the noticeable increase in prevalence from 2010 to 2012, diagnosis of both brucellosis and typhoid is important for early detection, and for raising public awareness on methods for preventing brucellosis in this setting.
PMCID: PMC4559071  PMID: 26337179
Trends; Brucellosis; Pastoralist communities
8.  Impacts of the 13-Valent Pneumococcal Conjugate Vaccine in Children 
Journal of Immunology Research  2015;2015:591580.
Applications of the heptavalent pneumococcal conjugate vaccine (PCV7) in the pediatric immunization schedule have dramatically reduced the incidence of pneumococcal diseases in both vaccinated children and unvaccinated individuals of all ages. However, increased infections caused by non-PCV7 serotypes have been reported by several groups. To overcome this problem, new vaccines covering more serotypes including the emerging serotypes have been developed. The 13-valent pneumococcal conjugate vaccine (PCV13) currently covers the 7 PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional serotypes 1, 3, 5, 6A, 7F, and 19A. After the first year of PCV13 applications in the immunization schedule in young children, global evaluation studies demonstrated that PCV13 provided a wider coverage and more effective prevention than PCV7 against invasive pneumococcal diseases (IPDs), mucosal pneumococcal diseases, and pneumococcal carriage. We reviewed the effects of PCV13 in the control of pneumococcal diseases in children based on previous studies.
PMCID: PMC4553318  PMID: 26351648
9.  Vitamin D and Alzheimer's Disease: Neurocognition to Therapeutics 
Alzheimer's disease (AD), the major cause of dementia worldwide, is characterized by progressive loss of memory and cognition. The sporadic form of AD accounts for nearly 90% of the patients developing this disease. The last century has witnessed significant research to identify various mechanisms and risk factors contributing to the complex etiopathogenesis of AD by analyzing postmortem AD brains and experimenting with animal and cell culture based models. However, the treatment strategies, as of now, are only symptomatic. Accumulating evidences suggested a significant association between vitamin D deficiency, dementia, and AD. This review encompasses the beneficial role of vitamin D in neurocognition and optimal brain health along with epidemiological evidence of the high prevalence of hypovitaminosis D among aged and AD population. Moreover, disrupted signaling, altered utilization of vitamin D, and polymorphisms of several related genes including vitamin D receptor (VDR) also predispose to AD or AD-like neurodegeneration. This review explores the relationship between this gene-environmental influence and long term vitamin D deficiency as a risk factor for development of sporadic AD along with the role and rationale of therapeutic trials with vitamin D. It is, therefore, urgently warranted to further establish the role of this potentially neuroprotective vitamin in preventing and halting progressive neurodegeneration in AD patients.
PMCID: PMC4553343  PMID: 26351614
10.  Advances in Breast Cancer: Pathways to Personalized Medicine 
Breast cancer is a complex disease caused by the progressive accumulation of multiple gene mutations combined with epigenetic dysregulation of critical genes and protein pathways. There is substantial interindividual variability in both the age at diagnosis and phenotypic expression of the disease. With an estimated 1,152,161 new breast cancer cases diagnosed worldwide per year, cancer control efforts in the postgenome era should be focused at both population and individual levels to develop novel risk assessment and treatment strategies that will further reduce the morbidity and mortality associated with the disease. The discovery that mutations in the BRCA1 and BRCA2 genes increase the risk of breast and ovarian cancers has radically transformed our understanding of the genetic basis of breast cancer, leading to improved management of high-risk women. A better understanding of tumor host biology has led to improvements in the multidisciplinary management of breast cancer, and traditional pathologic evaluation is being complemented by more sophisticated genomic approaches. A number of genomic biomarkers have been developed for clinical use, and increasingly, pharmacogenetic end points are being incorporated into clinical trial design. For women diagnosed with breast cancer, prognostic or predictive information is most useful when coupled with targeted therapeutic approaches, very few of which exist for women with triple-negative breast cancer or those with tumors resistant to chemotherapy. The immediate challenge is to learn how to use the molecular characteristics of an individual and their tumor to improve detection and treatment, and ultimately to prevent the development of breast cancer. The five articles in this edition of CCR Focus highlight recent advances and future directions on the pathway to individualized approaches for the early detection, treatment, and prevention of breast cancer.
PMCID: PMC4535810  PMID: 19088015
11.  A new duck circovirus sequence, detected in velvet scoter (Melanitta fusca) supports great diversity among this species of virus 
Virology Journal  2015;12:121.
The aim of this study was to investigate the presence of circoviruses in wild bird populations, in Poland. Circoviruses possess immuno-suppressive properties and might interfere with the health of wild birds.
83 birds, which belonged to 23 species, were tested with broad-range, nested PCR. The obtained PCR products were sequenced and new primers designed, to analyse the full-length, viral genome. A phylogenetic analysis was conducted, to find any relationship to known circoviruses.
The circovirus DNA sequence was found in 4 birds. All samples originated from the velvet scoter (Melanitta fusca) a marine duck from the Merginae sub-family. Birds which tested positive for the circovirus were found dead in fishing nets, off the Baltic coast. During post-mortem examination, carcasses of two of the scoters showed only light emaciation, while the two other birds appeared healthy. The obtained, full-length, circovirus sequence revealed 1,988 nucleotides and the presence of typical features (i.e. Cap, Rep and ORF3). Nucleotide similarity to other duck circoviruses was 84 to 86 %. Phylogenetic analysis of the complete genome and cap gene, indicated that the new circovirus is related to known duck circoviruses, especially to sub-types sometimes referred to as duck circovirus genotype 1, but not genotype 2.
In this study, we have reported a new duck circovirus sequence detected in the velvet scoter, a species of marine duck. Sequence comparison and phylogenetic analysis of the new virus sequence support previous reports that duck circovirus (DuCV) is a species with a high degree of diversity. The viral sequence obtained from the velvet scoter suggests that DuCV may infect birds from the Anatinae sub-family. More studies are needed to prove if the velvet scoter and other marine ducks act as a reservoir for DuCV.
PMCID: PMC4528844  PMID: 26253134
12.  Performance of 5-aminolevulinic-acid-based photodynamic diagnosis for radical prostatectomy 
BMC Urology  2015;15:78.
The aim of this study was to investigate whether we could detect positive surgical margins during open and laparoscopic radical prostatectomy by 5-aminolevulinic acid (ALA) photodynamic diagnosis (PDD) and mapping of red fluorescence in human prostate cancer cells.
All 52 patients were diagnosed with prostate cancer by biopsy. They had a positive core in the apex or highly suspicious positive margins. Open and laparoscopic radical prostatectomy was performed in 18 and 34 cases, respectively. One gram of ALA solution was given intraoperatively, orally through a stomach tube. An endoscopic PDD system, including a D-Light C, CCU Tricam SLII/3CCD CH Tricam-P PDD, and HOPKINS II Straight Forward Telescope 0°, was used. The D-Light C light source was equipped with a band-pass filter. The CCU Tricam SLII/3CCD CHTricam-P PDD video camera system was equipped with a long-pass filter. The laparoscopy optic component was equipped with a yellow long-pass filter.
One of the 52 patients had a red-fluorescent-positive margin of the excised whole prostate and the positive surgical margin was histologically confirmed. In the section of excised prostate, we obtained 141 biopsied samples. The sensitivity and specificity were 75.0 % and 87.3 %, respectively.
Intraoperative ALA-PDD is feasible. However, heat degeneration and length of positive surgical margin have crucial influences on red fluorescence. In future, a randomized clinical trial should be carried out.
PMCID: PMC4521460  PMID: 26232024
13.  Oncologic outcomes in men with metastasis to the prostatic anterior fat pad lymph nodes: a multi-institution international study 
BMC Urology  2015;15:79.
The presence of lymph nodes (LN) within the prostatic anterior fat pad (PAFP) has been reported in several recent reports. These PAFP LNs rarely harbor metastatic disease, and the characteristics of patients with PAFP LN metastasis are not well-described in the literature. Our previous study suggested that metastatic disease to the PAFP LN was associated with less severe oncologic outcomes than those that involve the pelvic lymph node (PLN). Therefore, the objective of this study is to assess the oncologic outcome of prostate cancer (PCa) patients with PAFP LN metastasis in a larger patient population.
Data were analyzed on 8800 patients from eleven international centers in three countries. Eighty-eight patients were found to have metastatic disease to the PAFP LNs (PAFP+) and 206 men had isolated metastasis to the pelvic LNs (PLN+). Clinicopathologic features were compared using ANOVA and Chi square tests. The Kaplan-Meier method was used to calculate the time to biochemical recurrence (BCR).
Of the eighty-eight patients with PAFP LN metastasis, sixty-three (71.6 %) were up-staged based on the pathologic analysis of PAFP and eight (9.1 %) had a low-risk disease. Patients with LNs present in the PAFP had a higher incidence of biopsy Gleason score (GS) 8–10, pathologic N1 disease, and positive surgical margin in prostatectomy specimens than those with no LNs detected in the PAFP. Men who were PAFP+ with or without PLN involvement had more aggressive pathologic features than those with PLN disease only. However, there was no significant difference in BCR-free survival regardless of adjuvant therapy. In 300 patients who underwent PAFP LN mapping, 65 LNs were detected. It was also found that 44 out of 65 (67.7 %) nodes were located in the middle portion of the PAFP.
There was no significant difference in the rate of BCR between the PAFP LN+ and PLN+ groups. The PAFP likely represents a landing zone that is different from the PLNs for PCa metastasis. Therefore, the removal and pathologic analysis of PAFP should be adopted as a standard procedure in all patients undergoing radical prostatectomy.
Electronic supplementary material
The online version of this article (doi:10.1186/s12894-015-0070-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4521494  PMID: 26231860
Lymph node metastases; Prostate anterior fat pad; Prostate cancer
14.  Treatment patterns and outcomes in BRAF V600E-mutant melanoma patients with brain metastases receiving vemurafenib in the real-world setting 
Cancer Medicine  2015;4(8):1205-1213.
Brain metastases are a common and serious complication among patients with metastatic melanoma. The selective BRAF inhibitor vemurafenib has demonstrated clinical efficacy in patients with BRAF V600E-mutant melanoma brain metastases (MBM). We examined the real-world application and clinical outcomes of vemurafenib in this patient population. Demographic, treatment patterns, response, and survival data were collected from medical charts. Clinical data on 283 patients with active BRAF V600E-mutant MBM treated with vemurafenib were provided by 70 US oncologists. Mean age was 57.2 years, 60.8% were male, 67.5% had ECOG performance status of 0–1, and 43.1% used corticosteroids at vemurafenib initiation. Median follow-up was 5.7 months. Following vemurafenib initiation, 48.1% of patients experienced intracranial response and 45.6% experienced extracranial response. The Kaplan–Meier estimate for overall survival was 59% at 12 months. Multivariate analyses showed associations between intracranial response and both corticosteroid use and vemurafenib as initial therapy after MBM diagnosis. Larger size (5–10 mm vs. <5 mm) and number of brain metastases (≥5 vs. <2) and progressive extracranial disease at treatment initiation were associated with decreased intracranial response and increased risk of disease progression. Multiple extracranial sites (2 vs. <2) and the absence of local treatments were also associated with increased risk of progression. Increased risk of death was associated with ≥2 extracranial disease sites, progressive extracranial disease, and ≥5 brain metastases. Subgroups of MBM patients may derive more benefit with vemurafenib, warranting prospective investigation.
PMCID: PMC4559032  PMID: 25991583
BRAF mutation; brain metastases; melanoma brain metastases; metastatic melanoma; vemurafenib
15.  Comparison of continence outcomes of early catheter removal on postoperative day 2 and 4 after laparoscopic radical prostatectomy: a randomized controlled trial 
BMC Urology  2015;15:77.
The optimal timing of catheter removal following laparoscopic radical prostatectomy (LRP) has not yet been determined. This prospective study was designed to compare the efficacy and safety of catheter removal on postoperative day (POD) 2 versus POD 4 after LRP and its impact on urinary continence outcomes.
One hundred and thirteen patients underwent LRP and were prospectively randomized into two groups: group 1 (n = 57) had the urinary catheter removed on POD 2 while group 2 (n = 56) had the catheter removed on POD 4. The urine loss ratio (ULR) was defined as the weight of urine loss in the pad divided by the daily micturition volume. Continence was defined as a pad-free status.
No significant differences were observed in clinical features between groups 1 and 2. Acute urinary retention (AUR) after catheter removal occurred in 21 patients (18.6 %) (13 (22.8 %) in group 1 and 8 (14.3 %) in group 2 (p = 0.244). The first-day mean ULR values were 1.16 ± 4.95 in group 1 and 1.02 ± 3.27 in group 2 (p = 0.870). The last-day mean ULR values were 0.57 ± 1.60 in group 1 and 2.78 ± 15.49 in group 2 (p = 0.353). Continence rates at 3, 6, 9, and 12 months were 21.8, 41.1, 58.0, and 71.4 % in group 1 and 34.5, 66.0, 79.2, and 83.7 % in group 2 (p = 0.138, 0.009, 0.024, and 0.146, respectively). In AUR cases, continence rates at 3, 6, 9, and 12 months were 0, 23.1, 38.5, and 54.5 % in group 1 and 37.5, 75.0, 87.5, and 87.5 % in group 2 (p = 0.017, 0.020, 0.027, and 0.127, respectively). A multivariate analysis identified AUR after catheter removal on POD 2 as the only predictive factor for incontinence 6 and 9 months after LRP (p = 0.030 and 0.018, respectively).
Our results demonstrated that early catheter removal on POD 2 after LRP may increase the risk of incontinence.
Trial registration
The study was registered as Clinical trial: (UMIN000014944); registration date: 12 March 2012.
PMCID: PMC4520008
Laparoscopic radical prostatectomy; Early catheter removal; Urinary incontinence; Prostate cancer
16.  Computer-aided transrectal ultrasound: does prostate HistoScanning™ improve detection performance of prostate cancer in repeat biopsies? 
BMC Urology  2015;15:76.
An imaging tool providing reliable prostate cancer (PCa) detection and localization is necessary to improve common diagnostic pathway with ultrasound targeted biopsies. To determine the performance of transrectal ultrasound (TRUS) augmented by prostate HistoScanningTM analysis (PHS) we investigated the detection of prostate cancer (PCa) foci in repeat prostate biopsies (Bx).
97 men with a mean age of 66.2 (44 – 82) years underwent PHS augmented TRUS analysis prior to a repeat Bx. Three PHS positive foci were defined in accordance with 6 bilateral prostatic sectors. Targeted Bx (tBx) limited to PHS positive foci and a systematic 14-core backup Bx (sBx) were taken. Results were correlated to biopsy outcome. Sensitivity, specificity, predictive accuracy, negative predictive value (NPV) and positive predictive value (PPV) were calculated.
PCa was found in 31 of 97 (32 %) patients. Detection rate in tBx was significantly higher (p < .001). Detection rate in tBx and sBx did not differ on patient level(p ≥ 0.7). PHS sensitivity, specificity, predictive accuracy, PPV and NPV were 45 %, 83 %, 80 %, 19 % and 95 %, respectively.
PHS augmented TRUS identifies abnormal prostatic tissue. Although sensitivity and PPV for PCa are low, PHS information facilitates Bx targeting to vulnerable foci and results in a higher cancer detection rate. PHS targeted Bx should be considered in patients at persistent risk of PCa.
PMCID: PMC4518605  PMID: 26223353
Prostate; Prostate cancer; Transrectal ultrasonography; HistoScanning; Prostate biopsy
17.  Autoimmune hemolytic anemia associated with renal urothelial cancer: A case report and literature review 
BMC Urology  2015;15:75.
Autoimmune hemolytic anemia (AIHA) is hemolytic anemia characterized by autoantibodies directed against red blood cells. AIHA can be induced by hematological neoplasms such as malignant lymphoma, but is rarely observed in the urological field. We report a case of renal urothelial cancer inducing Coombs-positive warm AIHA and severe thrombocytopenia that was responsive to nephroureterectomy.
Case presentation
A 52-year-old man presented with a 1-month history of general weakness and dizziness. Hemoglobin level was 4.2 g/dL, and direct and indirect Coombs tests both yielded positive results. Abdominal computed tomography revealed huge left hydronephrosis due to a renal pelvic tumor measuring 4.0 x 4.0 x 3.0 cm, and renal regional lymph-node involvement was also observed and suspected as metastasis. Corticosteroid therapy was administered, and nephroureterectomy was performed. After surgical resection, the hemoglobin level gradually normalized, and direct and indirect Coombs tests yielded negative results. We thus diagnosed warm AIHA associated with renal urothelial cancer.
To the best of our knowledge, this represents the first report of AIHA associated with renal urothelial cancer and severe thrombocytopenia responsive to nephroureterectomy. Renal urothelial cancer needs to be included in the differential diagnoses for warm AIHA, and nephroureterectomy represents a treatment option for AIHA.
PMCID: PMC4515913  PMID: 26215157
Autoimmune hemolytic anemia; Paraneoplastic syndromes; Renal urothelial cancer; Nephroureterectomy
18.  Therapeutic Effect of Saponin Rich Fraction of Achyranthes aspera Linn. on Adjuvant-Induced Arthritis in Sprague-Dawley Rats 
Autoimmune Diseases  2015;2015:943645.
Objective. Achyranthes aspera Linn. (AA) is used in folklore for the treatment of various inflammatory ailments and arthritis like conditions. Anti-inflammatory activity of saponin rich (SR) fraction of AA has been previously reported. The objective of this study was to assess the antiarthritic effect of SR fraction of Achyranthes aspera in adjuvant-induced arthritic rats. Methods. Arthritis was assessed by arthritis score, paw volume, changes in tibiotarsal joint thickness, hyperalgesic parameters, and spleen and thymus index. Haematological, serum, biochemical, and inflammatory cytokine and in vivo antioxidant parameters were measured on the last day of the study. Results. SR fraction significantly suppressed paw swelling and arthritic score and improved the pain threshold in motility and stair climbing tests. There was a reversal in the levels of altered parameters, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and antioxidant parameters like superoxide dismutase, catalase, glutathione, malondialdehyde, and nitric oxide. SR fraction significantly decreased plasma levels of tumor necrosis factor-alpha and interleukin-6. Moreover, histopathology revealed a significant reduction in synovial hyperplasia, inflammatory cell infiltration, and bone destruction in the joints. Conclusion. These observations explain the therapeutic benefit of SR fraction of AA in suppressing the progression of adjuvant-induced arthritis in rats.
PMCID: PMC4529882  PMID: 26273477
19.  The role of diagnostic ureteroscopy in the era of computed tomography urography 
BMC Urology  2015;15:74.
To examine the contemporary role of ureteroscopy in the diagnosis of upper urinary tract urothelial carcinoma.
We retrospectively evaluated 116 diagnostic ureteroscopies, performed in our institution to rule out primary UTUC. Demographics, cytological findings and interpretation of preoperative imaging were obtained. Ureteroscopic diagnosis and histological results were recorded and the predictive values of diagnostic studies were determined. Follow-up data was reviewed to evaluate the oncological outcomes in patients treated endoscopically.
The pre-ureteroscopic evaluation included CTU in 91 (78 %) patients. Positive and Negative predictive values of CTU were 76 and 80 %, respectively. Typical filling defect on CTU was demonstrated in 38 of 89 patients. UTUC has been ruled out in 9 patients (24 %) with suspicious filling defect on CTU. Endoscopic approach was implemented in 7 patients (18 %). During a median follow up period of 17 months (IQR, 9–25) none of the followed patients experienced disease progression.
Nephroureterectomy was spared from 42 % of patients who underwent diagnostic ureteroscopy for suspected UTUC, demonstrated on CTU. In about half of those patients tumor has been ruled out and the others were managed endoscopically. Therefore, diagnostic ureteroscopy is advised as a crucial step in confirming UTUC and treatment planning.
PMCID: PMC4515021  PMID: 26209444
Upper urinary tract urothelial carcinoma; Ureteroscopy; Computed tomography urography
20.  Extravascular stent management for migration of left renal vein endovascular stent in nutcracker syndrome 
BMC Urology  2015;15:73.
Nutcracker syndrome is an entity resulting from left renal vein compression by the aorta and the superior mesenteric artery, which leads to symptoms of hematuria or left flank pain. The alternative option of endovascular or extravascular stenting is very appealing because of the minimal invasive procedures. Stents in the renal vein can cause fibromuscular hyperplasia, proximal migration or embolization.
Case presentation
A 30-year-old female was diagnosed with nutcracker syndrome for severe left flank pain. After failed conservative approach, she underwent endovascular stenting and subsequently developed recurrent symptom for stent migration one month postoperatively. She underwent successful extravascular stenting with complete symptom resolution.
The extravascular stenting is an alternative option after migration of left renal vein endovascular stenting. The computed tomographic imaging was closely correlated to therapeutic interventions and stent migration.
PMCID: PMC4512087  PMID: 26205510
Nutcracker syndrome; Stent migration; Management
21.  Primary renal squamous cell carcinoma mimicking the renal cyst: a case report and review of the recent literature 
BMC Urology  2015;15:69.
Renal squamous cell carcinoma is a rare neoplasm with poor prognosis. Chronic irritation from nephrolithiasis and/or pyelonephritis is the leading cause.
Case presentation
We described a 51-year-old male patient who was admitted because of left flank pain. Ultrasonography showed a renal cyst containing calculus. However, contrast-enhanced ultrasonography and CT scan revealed an irregular-shaped mass derived from a calculi-containing cyst. Ultrasound guided biopsy confirmed the diagnosis of renal squamous cell carcinoma. The patient refused any further therapeutic management and died six months later.
Our present case emphasizes that the careful diagnostic work-up and use of multiple imaging modalities in cases of unusual renal calculi is quite necessary, since they may carry the risk of co-existing hidden malignancy.
PMCID: PMC4511242  PMID: 26201315
Kidney; Squamous cell carcinoma
22.  How do stone attenuation and skin-to-stone distance in computed tomography influence the performance of shock wave lithotripsy in ureteral stone disease? 
BMC Urology  2015;15:72.
Shock wave lithotripsy (SWL) is a noninvasive, safe, and efficient treatment option for ureteral stones. Depending on stone location and size, the overall stone-free rate (SFR) varies significantly. Failure of stone disintegration results in unnecessary exposure to shock waves and radiation and requires alternative treatment procedures, which increases medical costs. It is therefore important to identify predictors of treatment success or failure in patients who are potential candidates for SWL before treatment. Nowadays, noncontrast computed tomography (NCCT) provides reliable information on stone location, size, number, and total stone burden. The impact of additional information provided by NCCT, such as skin-to-stone distance (SSD) and mean attenuation value (MAV), on stone fragmentation in ureteral stone disease has hardly been investigated separately so far. Thus, the objective of this study was to assess the influence of stone attenuation, SSD and body mass index (BMI) on the outcome of SWL in ureteral stones.
We reviewed the medical records of 104 patients (80 men, 24 women) with ureteral stone disease treated consecutively at our institution with SWL between 2010 and 2013. MAV in Hounsfield Units (HU) and SSD were determined by analyzing noncontrast computed tomography images. Outcome of SWL was defined as successful (visible stone fragmentation on kidney, ureter, and bladder film (KUB)) or failed (absent fragmentation on KUB).
Overall success of SWL was 50 % (52 patients). Median stone attenuation was 956.9 HU (range 495–1210.8) in the group with successful disintegration and 944.6 (range 237–1302) in the patients who had absent or insufficient fragmentation. Median SSD was 125 mm (range 81–165 mm) in the group treated successfully and 141 mm (range 108–172 mm) in the patients with treatment failure. Unlike MAV (p = 0.37), SSD (p < 0.001) and BMI (p = 0.008) significantly correlated with treatment outcome.
The choice of treatment for ureteral stones should be based on stone location and size as considered in the AUA and EAU guidelines on urinary stone disease. In ambiguous cases, SSD and BMI can be used to assist in the decision. In this study, MAV showed no correlation with fragmentation rate of SWL.
PMCID: PMC4511972  PMID: 26201514
Ureteral stones; Treatment outcome; Shock wave lithotripsy; Hounsfield Units; Skin-to-stone distance
23.  Review by urological pathologists improves the accuracy of Gleason grading by general pathologists 
BMC Urology  2015;15:70.
Urologists use biopsy Gleason scores for patient counseling, prognosis prediction, and decision making. The accuracy of Gleason grading is very important. However, the variability of Gleason grading between general pathologists cannot be overlooked. Here we evaluate the discrepancy in the Gleason grading between 2 urologic pathologists and general pathologists as well as improvement in the accuracy of Gleason grading by general pathologists as a result of review by urologic pathologists.
The subjects enrolled in the study were 755 patients who underwent prostate needle biopsy at affiliate hospitals of Nara Medical University over a period of 2 years. The biopsy samples were diagnosed by general pathologists. All biopsy samples were sent to Nara Medical University where they were diagnosed by 2 urologic pathologists. The results were then returned to the general pathologists. We compared the diagnostic accuracy of the general pathologists with that of the urologic pathologists for the parameters of no malignancy, atypical small acinar proliferation, high grade prostatic intraepithelial neoplasia and Gleason score (6, 3 + 4, 4 + 3 and 8–10). We then evaluated the concordance rate between the general and urologic pathologists for each of four consecutive 6-month periods.
The overall concordance rate of urologic pathologists and general pathologists in the first, second, third and last 6-month periods was 71.8 % (140/198), 79.8 % (168/225), 89.7 % (166/185) and 89.9 % (133/148), respectively. The concordance rate of the Gleason score between urologic pathologists and general pathologists in the first, second, third and last 6-month periods was 47.5 %(38/80), 62.6 %(57/91),76.9 %(50/65) and 78.7 %(48/61), respectively, and the kappa value was 0.55, 0.68, 0.81 and 0.84, respectively. The concordance rate improved significantly over the course of each period (P = 0.04).
The concordance rate of the Gleason grading between the general pathologists and the urologic pathologists was 47.5 %. However, improvement of the concordance rate as a result of review by the urological pathologist could be seen.
PMCID: PMC4511985  PMID: 26201393
Gleason score; Prostate biopsy; General pathologist; Urological pathologist
24.  Flexible ureteroscopy training for surgeons using isolated porcine kidneys in vitro 
BMC Urology  2015;15:71.
To evaluate the feasibility of flexible ureteroscopy training by using isolated porcine kidneys and ureters in vitro.
Twenty young urologists were randomly divided into four groups. Overall performance was assessed based on a global rating scale, pass/fail rating, total time to complete task, learning curve, incidence of trauma, and perforations. The effect of training was determined by comparing their performance in baseline with that in the post-test.
After the training, average operation time significantly decreased from 18 ± 3.4 min to 11 ± 1.2 min (P < 0.05). The urologists exhibited a relatively stable performance level after the sixth operation. Significant differences were observed between pre-test and post-test with respect to the global rating scale and the pass/fail rating (P < 0.05). However, the incidence of mucosal trauma and perforations did not change significantly (P = 0.26 and 0.35, respectively).
The isolated porcine kidneys are convenient and intuitive models for young urologists to practice flexible ureteroscopy on.
Electronic supplementary material
The online version of this article (doi:10.1186/s12894-015-0067-9) contains supplementary material, which is available to authorized users.
PMCID: PMC4512109  PMID: 26201465
Ureteroscopes; Training; Porcine kidney; Teaching
25.  Primary melanoma of the prostate: case report and review of the literature 
BMC Urology  2015;15:68.
Primary melanoma of the prostate has an extremely rare incidence. Only five cases have been reported in the literature and prognosis is poor. The most likely origin of prostatic melanoma is the transitional epithelium of the prostatic urethra. Surgical care for primary melanoma of mucosal sites is less well established than for primary cutaneous melanoma, but excision of the primary is recommended if the patient has no systemic disease.
Case presentation
Here, we describe a case of primary malignant melanoma of the prostate. A 37-year-old male patient with history of both chemo- and radiation therapy for Hodgkin’s disease was admitted to the University Hospital Heidelberg on suspicion of pleomorphic sarcoma of the bladder. In-house diagnostic work-up revealed a malignant melanoma of the prostate. We then performed radical prostatectomy with extended lymphadenectomy. Despite presumably curative surgery, the patient suffered from early relapse of disease with pulmonary metastasis. Systemic chemotherapy and subsequent immuno-oncologic treatment was thereafter initiated.
Since prostatic melanoma is a rare disease and a melanoma metastasis of unknown primary is the differential diagnosis, a multidisciplinary approach including early imaging to rule out possible metastases and to search for another potentially existing primary is advisable. To prevent complications related to local tumor progression and to receive tissue for mutational analysis, we recommend complete surgical resection to reduce the tumor mass. Novel immune and targeted oncologic therapies can lead to an improved survival in some cases and support of clinical trials is needed.
PMCID: PMC4501120  PMID: 26169921
Prostate; Prostatic neoplasm; Prostatectomy; Ipilimumab; Nivolumab

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