PLoS One. 2012; 7(1): e30712
Fitzgerald JP, Nayak B, Shanmugasundaram K, Friedrichs W, Sudarshan S, Eid AA, Denapoli T, Parekh DJ, Gorin Y, Block K

Inflammatory cytokines are detected in the plasma of patients with renal cell carcinoma (RCC) and are associated with poor prognosis. However, the primary cell type involved in producing inflammatory cytokines and the biological significance in RCC remain unknown. Inflammation is associated with oxidative stress, upregulation of hypoxia inducible factor 1-alpha, and production of pro-inflammatory gene products. Solid tumors are often heterogeneous in oxygen tension together suggesting that hypoxia may play a role in inflammatory processes in RCC. Epithelial cells have been implicated in cytokine release, although the stimuli to release and molecular mechanisms by which they are released remain unclear. AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy status and a role for AMPK in the regulation of cell inflammatory processes has recently been demonstrated.We have identified for the first time that interleukin-6 and interleukin-8 (IL-6 and IL-8) are secreted solely from RCC cells exposed to hypoxia. Furthermore, we demonstrate that the NADPH oxidase isoform, Nox4, play a key role in hypoxia-induced IL-6 and IL-8 production in RCC. Finally, we have characterized that enhanced levels of IL-6 and IL-8 result in RCC cell invasion and that activation of AMPK reduces Nox4 expression, IL-6 and IL-8 production, and RCC cell invasion.Together, our data identify novel mechanisms by which AMPK and Nox4 may be linked to inflammation-induced RCC metastasis and that pharmacological activation of AMPK and/or antioxidants targeting Nox4 may represent a relevant therapeutic intervention to reduce IL-6- and IL-8-induced inflammation and cell invasion in RCC.

PLoS One. 2012; 7(1): e29623
Montecinos VP, Godoy A, Hinklin J, Vethanayagam RR, Smith GJ

Characterization of the mechanism(s) of androgen-driven human angiogenesis could have significant implications for modeling new forms of anti-angiogenic therapies for CaP and for developing targeted adjuvant therapies to improve efficacy of androgen-deprivation therapy. However, models of angiogenesis by human endothelial cells localized within an intact human prostate tissue architecture are until now extremely limited. This report characterizes the burst of angiogenesis by endogenous human blood vessels in primary xenografts of fresh surgical specimens of benign prostate or prostate cancer (CaP) tissue that occurs between Days 6-14 after transplantation into SCID mice pre-implanted with testosterone pellets. The wave of human angiogenesis was preceded by androgen-mediated up-regulation of VEGF-A expression in the stromal compartment. The neo-vessel network anastomosed to the host mouse vascular system between Days 6-10 post-transplantation, the angiogenic response ceased by Day 15, and by Day 30 the vasculature had matured and stabilized, as indicated by a lack of leakage of serum components into the interstitial tissue space and by association of nascent endothelial cells with mural cells/pericytes. The angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for α-SMA, Vimentin, Tenascin, Calponin, Desmin and Masson's trichrome, but the reactive stroma phenotype appeared to be largely independent of androgen availability. Transplantation-induced angiogenesis by endogenous human endothelial cells present in primary xenografts of benign and malignant human prostate tissue was preceded by induction of androgen-driven expression of VEGF by the prostate stroma, and was concurrent with and the appearance of a reactive stroma phenotype. Androgen-modulated expression of VEGF-A appeared to be a causal regulator of angiogenesis, and possibly of stromal activation, in human prostate xenografts.

J Minim Access Surg. 2012 Jan; 8(1): 25-6
Ganpule AP

J Minim Access Surg. 2012 Jan; 8(1): 13-5
Patankar SB, Shah RB, Oza NN

Today, in the era of minimally invasive surgery, paediatric laparoscopy has become widely popular. Extra-adrenal pheochromocytoma is a very rare entity, especially in the paediatric age group and utility of the laparoscopic approach is not established in this population. Early diagnosis and surgical excision are integral part of treatment of childhood pheochromocytoma. We present a case study of a child with hormonally active extra-adrenal pheochromocytoma that was resected laparoscopically. Laparoscopic approach provides excellent exposure with magnification and allows proper identification of the tumour and its relation to surrounding structures; complete resection of tumour was achieved with adequate vascular control. With our initial experience, we suggest laparoscopic resection is an appropriate and feasible tool in such cases.

J Infect Chemother. 2012 Feb 4;
Hamasuna R, Takahashi S, Uehara S, Matsumoto T

Detection of Neisseria gonorrhoeae (NG) or Chlamydia trachomatis (CT) from the pharynx of women or men is not uncommon. However, there is no recommendation how urologists should care for the pharyngeal infection of men with urethritis in Japan. The aim of this study is to clarify the prevalence of NG or CT infection in the pharynx of men and to show a recommendation for urologists. The Japanese reports about the detection of NG or CT from the pharynx or the oral cavity of men in Japan are reviewed in the literature from 1990 to 2011. The prevalence of NG or CT in the pharynx was 4% or 6% in men who attended clinics, and 20% or 6% in men who were positive for NG or CT from genital specimens, respectively. Single 1-g dose ceftriaxone was recommended to treat pharyngeal NG, but no evidence was found for pharyngeal CT. There was not enough evidence for recommendation. However, when men with urethritis only caused by NG or CT are treated through the guideline of the Japanese Society of Sexually Transmitted Infection, we do not think additional tests or treatment for the pharynx are needed when a single 1-g dose ceftriaxone for gonococcal urethritis or a single 1- or 2-g dose azithromycin is prescribed for chlamydial urethritis in Japan.

Jpn J Radiol. 2012 Feb 3;
Nomura T, Hirai K, Yamasaki M, Inoue T, Takahashi M, Kawashima T, Sato F, Mimata H

PURPOSE: There is little definitive evidence to guide the use of prophylactic antibiotics for prostate brachytherapy. The purpose of this study is to evaluate the incidence of postimplant infections in patients who receive antimicrobial prophylaxis with pazufloxacin (PZFX). MATERIALS AND METHODS: A total of 84 patients who underwent prostate brachytherapy received a single intravenous dose of PZFX at 500 mg perioperatively for 1 day. No postimplant antibiotic medication was prescribed. Urinalysis, plasma white blood cell (WBC) count, and C reactive protein (CRP) levels were evaluated before the implantation, on the day after implantation, and on the 7th and 28th days after brachytherapy. RESULTS: None of the 84 patients (0.0%) developed a symptomatic urinary tract infection or had febrile infectious complications after brachytherapy. There were statistically significant elevations in the levels of erythrocytes, leukocytes, bacteria in urine, plasma WBC and CRP postoperatively, but these values did not exceed the normal range or were only slightly elevated on the day after brachytherapy (day 1) and on day 7. All laboratory examinations had returned to the normal range on day 28. CONCLUSION: Single-dose therapy with fluoroquinolone helps to prevent infections after prostate brachytherapy.

J Am Soc Nephrol. 2012 Feb 2;
Sedrakyan S, Da Sacco S, Milanesi A, Shiri L, Petrosyan A, Varimezova R, Warburton D, Lemley KV, De Filippo RE, Perin L

Injection of amniotic fluid stem cells ameliorates the acute phase of acute tubular necrosis in animals by promoting proliferation of injured tubular cells and decreasing apoptosis, but whether these stem cells could be of benefit in CKD is unknown. Here, we used a mouse model of Alport syndrome, Col4a5(-/-) mice, to determine whether amniotic fluid stem cells could modify the course of progressive renal fibrosis. Intracardiac administration of amniotic fluid stem cells before the onset of proteinuria delayed interstitial fibrosis and progression of glomerular sclerosis, prolonged animal survival, and ameliorated the decline in kidney function. Treated animals exhibited decreased recruitment and activation of M1-type macrophages and a higher proportion of M2-type macrophages, which promote tissue remodeling. Amniotic fluid stem cells did not differentiate into podocyte-like cells and did not stimulate production of the collagen IVa5 needed for normal formation and function of the glomerular basement membrane. Instead, the mechanism of renal protection was probably the paracrine/endocrine modulation of both profibrotic cytokine expression and recruitment of macrophages to the interstitial space. Furthermore, injected mice retained a normal number of podocytes and had better integrity of the glomerular basement membrane compared with untreated Col4a5(-/-) mice. Inhibition of the renin-angiotensin system by amniotic fluid stem cells may contribute to these beneficial effects. In conclusion, treatment with amniotic fluid stem cells may be beneficial in kidney diseases characterized by progressive renal fibrosis.

Urol Int. 2012 Jan 31;
Shigemura K, Motoyama S, Yamashita M

Background: The comparison of systematic prostate biopsies (PBx) with PBx including additional cores based on magnetic resonance imaging (MRI) of lesions suspicious for prostate cancer (PCa) has been controversial. This study focuses on additional cores based on MRI findings for better cancer detection. Methods: Data were collected from 491 men who underwent transrectal ultrasound-guided PBx: a 12-core PBx (group 1: 395 cases) and a 12-core PBx plus 1-3 additional cores based on MRI (group 2: 96 cases). Comparison of two groups revealed how the additional cores taken with MRI findings affected PCa detection. Results: Group 1 had 205 cases (51.9%) and group 2 had 55 cases (57.3%) of PCa detected. This difference was not statistically significant (p = 0.3444). Only 1 of the 55 patients (1.82%) in group 2 had cancer only in the additional cores based on MRI. In other words, only 1/96 (1.04%) patients was diagnosed with PCa only by the additional core PBx. Conclusions: We suggest that systematic 12-core PBx (sextant peripheral zone + 4 transitional zone + 2 far lateral peripheral zone) can be considered an excellent tool for PCa detection and there may be no need for additional cores based on MRI findings for PCa detection.

Genome Res. 2012 Feb; 22(2): 183-7
Brooks JD

Early detection and definitive treatment of cancer have been shown to decrease death and suffering in epidemiologic and intervention studies. Application of genomic approaches to many malignancies has produced thousands of candidate biomarkers for detection and prognostication, yet very few have become established in clinical practice. Fundamental issues related to tumor heterogeneity, cancer progression, natural history, and biomarker performance have provided challenges to biomarker development. Technical issues in biomarker assay detection limits, specificity, clinical deployment, and regulation have also slowed progress. The recent emergence of biomarkers and molecular imaging strategies for treatment selection and monitoring demonstrates the promise of cancer biomarkers. Organized efforts by interdisciplinary teams will spur progress in cancer diagnostics.

Actas Urol Esp. 2012 Jan 31;
Paick JS, Park K, Kim SW, Park JW, Kim JJ, Kim MS, Park JY

OBJECTIVE: We investigated hypoxia inducible factor-1α (HIF-1α), connective tissue growth factor (CTGF) expression and fibrosis in the testis of rats with surgically induced varicocele. MATERIAL AND METHODS: A total of 47 adult male Sprague-Dawley rats were arranged in 3 groups, namely group 1 (varicocele operation 4 weeks ago, n=10; sham operation 4 weeks ago, n=5), group 2 (8 weeks, n=11; n=5), and group 3 (12 weeks, n=11; n=5). The rats in every group underwent bilateral orchiectomy 4, 8, and 12 weeks after the operations, respectively. HIF-1α and CTGF expression of both testes in group 3 were studied by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Fibrotic change was assessed by quantitative image analysis. RESULTS: HIF-1α mRNA expression in testes tissues in varicocele operation and sham controls showed no significant differences in RT-PCR. However, CTGF mRNA expressions in left testes were found to be significantly different between varicocele operation and sham controls. HIF-1α staining was present in both testes of all specimens and CTGF staining was present in 10 left and 8 right testes of 11 specimens. However HIF-1α and CTGF staining were absent in control group. There were significant fibrotic changes of both testes in groups 2 and 3. There were significant differences in fibrotic change along the durations of surgical varicocele. CONCLUSIONS: This study reveals that experimental varicocele in the rat is associated with HIF-1α and CTGF expression and it is accompanied by fibrotic change in the testis.

Urol Oncol. 2012 Jan 31;
Straub J, Strittmatter F, Karl A, Stief CG, Tritschler S

OBJECTIVES: To determine accuracy of upper tract cytology and ureteroscopic biopsy according to the 2004 World Health Organization (WHO) classification in predicting the correct tumor grade in patients with urothelial cancer of the upper urinary tract (UUT-UC). METHODS: Pathology reports of 77 nephroureterectomy specimens were retrospectively analyzed for tumor grade and compared with preoperatively gained cytology and ureteroscopic biopsy results. For analysis, the 2004 WHO classification was used. RESULTS: Overall sensitivity of cytology and biopsy in diagnosis of UUT-UC was 64% and 74%, respectively. Accuracy of cytology and biopsy in predicting high grade cancer was 53% and 58%, respectively. Combination of cytology and biopsy could improve sensitivity (84%) and accuracy (68%), but even for this combination, 15% of high grade tumors were misinterpreted as low grade cancer. CONCLUSION: Our results show only limited accuracy for preoperative cytology and ureterorenoscopically performed biopsies in the prediction of the correct tumor grading of an UUT-UC. Therefore, we suggest the use of additional diagnostic procedures before the decision for definitive surgical treatment in patients with UUT-UC is made.

Urol Oncol. 2012 Jan 31;
Svatek RS, Rosenberg JE, Galsky MD, Lee CT, Latini DM, Bochner BH, Weizer AZ, Apolo AB, Sridhar SS, Kamat AM, Hansel D, Flaig TW, Smith ND, Lotan Y

The 6th Annual Bladder Cancer Think Tank brought together a multidisciplinary group of clinicians, researchers, and representatives from the National Cancer Institute and Industry in an effort to advance bladder cancer research efforts. This year's meeting comprised panel discussions and research involving 5 separate working groups, including the Survivorship, Clinical Trials, Standardization of Care, Data Mining, and Translational Science working groups. In this manuscript, the accomplishments and objectives of the working groups are summarized. Notable efforts include: (1) the development of a survivorship care plan for early and late-stage bladder cancer; (2) the development of consensus criteria for eligibility and endpoints for bladder cancer clinical trials; (3) an improved understanding of current practice patterns regarding the use of perioperative chemotherapy in an effort to standardize care; (4) creation of a comprehensive handbook to assist researchers with developing bladder cancer databases; and (5) identification of response to therapy of high-grade non muscle invasive disease through a collaborative exchange of expertise and resources.