Publications by authors named "Barod R"

39 Publications

Urinary fistula after robot-assisted partial nephrectomy: a multicentre analysis of 1 791 patients.

BJU Int 2016 Jan 6;117(1):131-7. Epub 2015 Sep 6.

Division of Urology, Washington University School of Medicine, St. Louis, MO, USA.

Objective: To evaluate the incidence of and risk factors for a urine leak in a large multicentre, prospective database of robot-assisted partial nephrectomy (RPN).

Patients And Methods: A database of 1 791 RPN from five USA centres was reviewed for urine leak as a complication of RPN. Patient and tumour characteristics were compared between patients with and those without postoperative urine leaks. Fisher's exact test was used for qualitative variables and Wilcoxon sum-rank tests were used for quantitative variables. A review of the literature on PN and urine leak was conducted.

Results: Urine leak was noted in 14/1 791 (0.78%) patients who underwent RPN. The mean (sd) nephrometry score of the entire cohort was 7.2 (1.9), and 8.0 (1.9) in patients who developed urine leak. The median (range) postoperative day of presentation was 13 (3-32) days. Patients with urine leak presented in delayed fashion with fever (two of the 14 patients, 14%), gastrointestinal complaints (four patients, 29%), and pain (five patients, 36%). Eight of the 14 patients (57%) required admission, while eight (57%) and nine (64%) had a drain or stent placed, respectively. Drains and stents were removed after a median (range) of 8 (4-13) days and 21 (8-83) days, respectively. Variables associated with urine leak included tumour size (P = 0.021), hilar location (P = 0.025), operative time (P = 0.006), warm ischaemia time (P = 0.005), and pelvicalyceal repair (P = 0.018). Upon literature review, the historical incidence of urine leak ranged from 1.0% to 17.4% for open PN and 1.6-16.5% for laparoscopic PN.

Conclusion: The incidence of urine leak after RPN is very low and may be predicted by some preoperative factors, affording better patient counselling of risks. The low urinary leak rate may be attributed to the enhanced visualisation and suturing technique that accompanies the robotic approach.
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http://dx.doi.org/10.1111/bju.13249DOI Listing
January 2016

Endovascular Extraction of Caval Tumor Thrombus to Facilitate Minimally Invasive Cytoreductive Nephrectomy for Metastatic Kidney Cancer.

Eur Urol 2015 Jul 3;68(1):167-8. Epub 2015 Apr 3.

Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI, USA.

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http://dx.doi.org/10.1016/j.eururo.2015.03.039DOI Listing
July 2015

Primary prevention and vaccination for penile cancer.

Ther Adv Urol 2013 Jun;5(3):161-9

Department of Urology, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.

The outcome of penile cancer is proportional to the stage at presentation. Strategies aimed at primary prevention would have a clear advantage, both for the individual and in terms of health economics. A number of preventative measures could be employed, including circumcision, smoking cessation, education on hygiene and human papillomavirus (HPV) prevention. There is a high prevalence of HPV infection associated with penile cancer worldwide. The recent development of HPV vaccines has facilitated interest in their use for the prevention of penile cancer. In this article we review the literature surrounding penile cancer prevention and HPV vaccination in men.
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http://dx.doi.org/10.1177/1756287212465456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655354PMC
June 2013

Epigenetic regulation of HIF-1α in renal cancer cells involves HIF-1α/2α binding to a reverse hypoxia-response element.

Oncogene 2012 Feb 15;31(8):1065-72. Epub 2011 Aug 15.

Stem Cell and Cancer Biology Group, Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, GuangzhouInstitutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, China.

Inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene underlies the majority of sporadic clear cell renal cell carcinomas (CCRCCs) and is also responsible for the hereditary VHL cancer syndrome. VHL loss of function results in constitutive stabilization of hypoxia-inducible factors (HIF-1α and HIF-2α) due to insufficient proteolysis in the presence of oxygen. This activates multiple genes relevant to tumorigenesis, allowing cells to acquire further mutations and undergo malignant transformation. However, the specific role of each HIF-α subunit in CCRCC tumorigenesis is not yet well understood. The current paradigm supports that in the first stages of CCRCC formation the stabilization of HIF-1α is dominant and this limits proliferation, but later on HIF-2α increases and this induces a more aggressive cell behavior. Understanding how this transition happens is highly relevant, as it may provide novel ways to treat these cancers. Here, we show that VHL inactivation in CCRCC cells results in HIF-1α/2α-dependent downregulation of HIF-1α mRNA through direct binding of either subunit to a reverse hypoxia-response element in the HIF-1α proximal promoter. This binding activates a series of repressive histone modification marks including histone 3 lysine 27 trimethylation (H3K27me3) to make the changes stable, and if overturned reduces CCRCC cell proliferation due to excessive HIF-1α expression level. Our findings thus help understand how HIF-α subunits influence each other and also reinforce the idea that epigenetic mechanisms are a key step of CCRCC progression.
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http://dx.doi.org/10.1038/onc.2011.305DOI Listing
February 2012

Factor inhibiting HIF (FIH-1) promotes renal cancer cell survival by protecting cells from HIF-1α-mediated apoptosis.

Br J Cancer 2011 Mar 8;104(7):1151-9. Epub 2011 Mar 8.

Centre for Cell Signalling and Molecular Genetics, Rayne Institute, University College London, London, WC1E 6JF, UK.

Background: Clear cell renal cell carcinoma (CCRCC) is the commonest form of kidney cancer. Up to 91% have biallelic inactivation of VHL, resulting in stabilisation of HIF-α subunits. Factor inhibiting HIF-1 is an enzyme that hydroxylates HIF-α subunits and prevents recruitment of the co-activator CBP/P300. An important question is whether FIH-1 controls HIF activity in CCRCC.

Methods: Human VHL defective CCRCC lines RCC10, RCC4 and 786-O were used to determine the role of FIH-1 in modulating HIF activity, using small interfering RNA knockdown, retroviral gene expression, quantitative RT-PCR, western blot analysis, Annexin V and propidium iodide labelling.

Results: Although it was previously suggested that FIH-1 is suppressed in CCRCC, we found that FIH-1 mRNA and protein are actually present at similar levels in CCRCC and normal kidney. The FIH-1 inhibition or knockdown in the VHL defective CCRCC lines RCC10 and RCC4 (which express both HIF-1α and HIF-2α) resulted in increased expression of HIF target genes. In the 786-O CCRCC cell line, which expresses only HIF-2α, FIH-1 attenuation showed no significant effect on expression of these genes; introduction of HIF-1α resulted in sensitivity of HIF targets to FIH-1 knockdown. In RCC4 and RCC10, knockdown of FIH-1 increased apoptosis. Suppressing HIF-1α expression in RCC10 prevented FIH-1 knockdown from increasing apoptosis.

Conclusion: Our results support a unifying model in which HIF-1α has a tumour suppressor action in CCRCC, held in check by FIH-1. Inhibiting FIH-1 in CCRCC could be used to bias the HIF response towards HIF-1α and decrease tumour cell viability.
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http://dx.doi.org/10.1038/bjc.2011.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068507PMC
March 2011

A report of succinate dehydrogenase B deficiency associated with metastatic papillary renal cell carcinoma: successful treatment with the multi-targeted tyrosine kinase inhibitor sunitinib.

BMJ Case Rep 2009 16;2009. Epub 2009 Feb 16.

Royal Marsden NHS Foundation Trust, Medical Oncology, London, SW3 6JJ, UK.

Unlabelled: We report a patient who initially presented with an abdominal paraganglioma and subsequently metastatic papillary cell renal cancer. Genetic analysis revealed a 141 G>A (exon 2) Trp47X mutation within the succinate dehydrogenase B gene. Treatment with the novel multi-targeted tyrosine kinase inhibitor sunitinib resulted in a sustained partial response and reduced the level of the angiogenic marker PIGF.

Trial Registration Number: a6181037.
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http://dx.doi.org/10.1136/bcr.08.2008.0732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028009PMC
November 2011

Regulation of renal epithelial tight junctions by the von Hippel-Lindau tumor suppressor gene involves occludin and claudin 1 and is independent of E-cadherin.

Mol Biol Cell 2009 Feb 10;20(3):1089-101. Epub 2008 Dec 10.

Division of Medicine, Rayne Institute, University College London, WC1E 6JJ, London, United Kingdom.

Epithelial-to-mesenchymal transitions (EMT) are important in renal development, fibrosis, and cancer. Loss of function of the tumor suppressor VHL leads to many features of EMT, and it has been hypothesized that the pivotal mediator is down-regulation of the adherens junction (AJ) protein E-cadherin. Here we show that VHL loss-of-function also has striking effects on the expression of the tight junction (TJ) components occludin and claudin 1 in vitro in VHL-defective clear cell renal cell carcinoma (CCRCC) cells and in vivo in VHL-defective sporadic CCRCCs (compared with normal kidney). Occludin is also down-regulated in premalignant foci in kidneys from patients with germline VHL mutations, consistent with a contribution to CCRCC initiation. Reexpression of E-cadherin was sufficient to restore AJ but not TJ assembly, indicating that the TJ defect is independent of E-cadherin down-regulation. Additional experiments show that activation of hypoxia inducible factor (HIF) contributes to both TJ and AJ abnormalities, thus the VHL/HIF pathway contributes to multiple aspects of the EMT phenotype that are not interdependent. Despite the independent nature of the defects, we show that treatment with the histone deacetylase inhibitor sodium butyrate, which suppresses HIF activation, provides a method for reversing EMT in the context of VHL inactivation.
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http://dx.doi.org/10.1091/mbc.e08-06-0566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633394PMC
February 2009

The clinical value and cost of a district hospital urodynamic unit.

Br J Urol 1982 Dec;54(6):635-7

A retrospective review has shown that urodynamic studies were useful in the diagnosis of 87% of our patients and were diagnostic in 43%. The cost per patient was 43 pounds, which compares favourably with urography (35 pounds) an in-patient cystoscopy (104 pounds). Provided that more than 200 patients a year are studied, the expense and effort of running the urodynamic unit are justified. We now perform urodynamic studies routinely in patients with complex lower urinary tract symptoms, prior to intravenous urography and cystoscopy.
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http://dx.doi.org/10.1111/j.1464-410x.1982.tb13613.xDOI Listing
December 1982
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