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E-cigarettes and Urologic Health: A Collaborative Review of Toxicology, Epidemiology, and Potential Risks

Abstract Context

Use of electronic cigarettes (ECs) is on the rise in most high-income countries. Smoking conventional cigarettes is a known risk factor for urologic malignancy incidence, progression, and mortality, as well as for other urologic health indicators. The potential impact of EC use on urologic health is therefore of clinical interest to the urology community.

Objective

To review the available data on current EC use, including potential benefits in urologic patients, potential issues linked to toxicology of EC constituents, and how this might translate into urologic health risks.

Evidence acquisition

A Medline search was carried out in August 2016 for studies reporting urologic health outcomes and EC use. Snowballing techniques were also used to identify relevant studies from recent systematic reviews. A narrative synthesis of data around EC health outcomes, toxicology, and potential use in smoking cessation and health policy was carried out.

Evidence synthesis

We found no studies to date that have been specifically designed to prospectively assess urologic health risks, even in an observational setting. Generating such data would be an important contribution to the debate on the role of ECs in public health and clinical practice. There is evidence from a recent Cochrane review of RCTs that ECs can support smoking cessation. There are emerging data indicating that potentially harmful components of ECs such as tobacco-specific nitrosamines, polyaromatic hydrocarbons, and heavy metals could be linked to possible urologic health risks.

Conclusions

ECs might be a useful tool to encourage cessation of conventional cigarette smoking. However, data collection around the specific impact of ECs on urologic health is needed to clarify the possible patient benefits, outcomes, and adverse events.

Patient summary

While electronic cigarettes might help some people to stop smoking, their overall impact on urologic health is not clear.

Take Home Message

While electronic cigarettes might help some people to stop smoking, it is not clear if they may be bad for urologic health.

Keywords: Electronic cigarettes, Smoking cessation, Toxicology, Urologic health.

Footnotes

a Faculty of Health and Wellbeing, Sheffield Hallam University, Sheffield, UK

b Institute for Social Marketing and UK Centre for Tobacco and Alcohol Studies, University of Stirling, Stirling, UK

c National Institute for Health Innovation, University of Auckland, Auckland, New Zealand

d Academic Urology Unit, Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

e Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

f Surveillance and Health Services Research, American Cancer Society, Atlanta, GA, USA

g Wolfson Institute of Preventative Medicine and UK Centre for Tobacco and Alcohol Studies, Queen Mary University of London, London, UK

h Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

Corresponding author. Faculty of Health and Wellbeing, Sheffield Hallam University, Collegiate Crescent, Sheffield S10 2BP, UK. Tel. +44 114 2255396.

Article information

PII: S0302-2838(16)30926-5
DOI: 10.1016/j.eururo.2016.12.022
© 2017 Published by Elsevier B.V.

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Liquid Biopsy Analysis of FGFR3 and PIK3CA Hotspot Mutations for Disease Surveillance in Bladder Cancer

Abstract Background

Disease surveillance in patients with bladder cancer is important for early diagnosis of progression and metastasis and for optimised treatment.

Objective

To develop urine and plasma assays for disease surveillance for patients with FGFR3 and PIK3CA tumour mutations.

Design, setting, and participants

Droplet digital polymerase chain reaction (ddPCR) assays were developed and tumour DNA from two patient cohorts was screened for FGFR3 and PIK3CA hotspot mutations. One cohort included 363 patients with non–muscle-invasive bladder cancer (NMIBC). The other cohort included 468 patients with bladder cancer undergoing radical cystectomy (Cx). Urine supernatants (NMIBC n = 216, Cx n = 27) and plasma samples (NMIBC n = 39, Cx n = 27) from patients harbouring mutations were subsequently screened using ddPCR assays.

Outcome measurements and statistical analysis

Progression-free survival, recurrence-free survival, and overall survival were measured. Fisher's exact test, the Wilcoxon rank-sum test and Cox regression analysis were applied.

Results and limitations

In total, 36% of the NMIBC patients (129/363) and 11% of the Cx patients (44/403) harboured at least one FGFR3 or PIK3CA mutation. Screening of DNA from serial urine supernatants from the NMIBC cohort revealed that high levels of tumour DNA (tDNA) were associated with later disease progression in NMIBC (p = 0.003). Furthermore, high levels of tDNA in plasma samples were associated with recurrence in the Cx cohort (p = 0.016). A positive correlation between tDNA levels in urine and plasma was observed (correlation coefficient 0.6). The retrospective study design and low volumes of plasma available for analysis were limitations of the study.

Conclusions

Increased levels of FGFR3 and PIK3CA mutated DNA in urine and plasma are indicative of later progression and metastasis in bladder cancer.

Patient summary

Urine and plasma from patients with bladder cancer may be monitored for diagnosis of progression and metastasis using mutation assays.

Take Home Message

Detection of hotspot mutations in FGFR3 and PIK3CA in liquid biopsies may allow efficient prediction of aggressiveness and surveillance of relapse in patients with bladder cancer.

Keywords: Biomarker, Cell-free DNA, Liquid biopsy, Personalised analysis, FGFR3, PIK3CA, Droplet digital polymerase chain reaction.

Footnotes

a Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark

b Department of Pathology, Aarhus University Hospital, Aarhus, Denmark

c Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands

d Department of Oncology, Aarhus University Hospital, Aarhus, Denmark

e Department of Urology, Aarhus University Hospital, Aarhus, Denmark

Corresponding author. Department of Molecular Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard, DK-8200 Aarhus N, Denmark. Tel. +45 78455320.

Article information

PII: S0302-2838(16)30920-4
DOI: 10.1016/j.eururo.2016.12.016
© 2016 European Association of Urology, Published by Elsevier B.V.

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Scientists uncover new way to defeat therapy-resistant prostate cancer

MedicalNewsToday - Fri, 01/06/2017 - 08:00
A new study led by scientists from the Florida campus of The Scripps Research Institute (TSRI) sheds light on a signaling circuit in cells that drives therapy resistance in prostate cancer.
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Urolithiasis in Children: Metabolic Workup is Essential in All!

Urology (Gold Journal) In Press - Fri, 01/06/2017 - 00:00
We read the recent paper by Bevill et al.[1] on pediatric urolithiasis with great interest. Evaluation in children with urolithiasis is considered mandatory[2], as this may reveal modifiable risk factors that can guide preventive therapy. With such prevention, stone recurrence and urolithiasis associated renal damage may be minimalized.
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Our Metabolic Findings in First Time Pediatric Stone Formers Questions the Need for a Full Metabolic Evaluation in Every Child

Urology (Gold Journal) In Press - Fri, 01/06/2017 - 00:00
In response, we agree, and the literature would suggest, that there are several different ways to define hypercalciuria1. We chose to use 250 mg/day, which is the standard value utilized in adults, as most of our study cohort was older. However, if we were to use >4 mg/kg/day to define hypercalciuria in our study population, we believe that it is better to use actual data, rather than to make assumptions. Within our cohort we found an average urine calcium level of 1.7 mg/kg/day (0.1-6.2 mg/kg day) and only 3 (3%) of our patients were found to have hypercalciuria (as defined as > 4 mg/kg/day).
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Villous Adenoma in Renal Pelvis with Manifestation of Percutaneous Fistula and Mucus Secretion

Urology (Gold Journal) In Press - Fri, 01/06/2017 - 00:00
A 70-year-old man, complaining of percutaneous fistula with jelly-like yellow mucus in right kidney for a month, was admitted to our department. From computer tomography, stones and severe hydronephrosis but no suspicious mass was found in right kidney. Nephrectomy of right kidney was performed and pathological examination revealed a villous adenoma in renal pelvis with moderate to severe atypical hyperplasia of glandular epithelium. Primary villous adenoma in renal pelvis is rare and believed to be related to chronic irritation of stone and inflammation.
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, , and are Novel Prognostic Markers in Renal Cell Carcinoma

Urology (Gold Journal) In Press - Fri, 01/06/2017 - 00:00
To identify and validate novel prognostic marker genes in clear cell renal cell carcinoma (RCC) that are increasingly expressed during tumor progression.
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Re: A miR-192-EGR1-HOXB9 Regulatory Network Controls the Angiogenic Switch in Cancer

S. Y. Wu, R. Rupaimoole, F. Shen, S. Pradeep, C. V. Pecot, C. Ivan, A. S. Nagaraja, K. M. Gharpure, E. Pham, H. Hatakeyama, M. H. McGuire, M. Haemmerle, V. Vidal-Anaya, C. Olsen, C. Rodriguez-Aguayo, J. Filant, E. A. Ehsanipour, S. M. Herbrich, S. N. Maiti, L. Huang, J. H. Kim, X. Zhang, H. D. Han, G. N. Armaiz-Pena, E. G. Seviour, S. Tucker, M. Zhang, D. Yang, L. J. Cooper, R. Ali-Fehmi, M. Bar-Eli, J. S. Lee, P. T. Ram, K. A. Baggerly, G. Lopez-Berestein, M. C. Hung and A. K. Sood
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Re: Genomic Characterization of Sarcomatoid Transformation in Clear Cell Renal Cell Carcinoma

M. Bi, S. Zhao, J. W. Said, M. J. Merino, A. J. Adeniran, Z. Xie, C. B. Nawaf, J. Choi, A. S. Belldegrun, A. J. Pantuck, H. M. Kluger, K. Bilgüvar, R. P. Lifton and B. Shuch
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Re: mTORC1-Mediated Inhibition of Polycystin-1 Expression Drives Renal Cyst Formation in Tuberous Sclerosis Complex

M. Pema, L. Drusian, M. Chiaravalli, M. Castelli, Q. Yao, S. Ricciardi, S. Somlo, F. Qian, S. Biffo and A. Boletta
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Re: Daniel E. Spratt, Herbert A. Vargas, Zachary S. Zumsteg, et al. Patterns of Lymph Node Failure after Dose-escalated Radiotherapy: Implications for Extended Pelvic Lymph Node Coverage. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2016.07...

Refers to article:

Patterns of Lymph Node Failure after Dose-escalated Radiotherapy: Implications for Extended Pelvic Lymph Node Coverage

Daniel E. Spratt, Hebert A. Vargas, Zachary S. Zumsteg, Jennifer S. Golia Pernicka, Joseph R. Osborne, Xin Pei and Michael J. Zelefsky

Accepted 22 July 2016

January 2017 (Vol. 71, Issue 1, pages 37 - 43)

Footnotes

a Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy

b Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy

c Department of Nuclear Medicine, San Raffaele Scientific Institute, Milan, Italy

Corresponding author. Department of Radiation Oncology, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy. Tel. +39 022 6437634; Fax: +39 022 6433855.

Article information

PII: S0302-2838(16)30925-3
DOI: 10.1016/j.eururo.2016.12.021
© 2016 European Association of Urology, Published by Elsevier B.V.

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Re: Inherited DNA-repair Gene Mutations in Men with Metastatic Prostate Cancer

Footnotes

Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

Corresponding author. Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.

Article information

PII: S0302-2838(16)30922-8
DOI: 10.1016/j.eururo.2016.12.018
© 2016 Published by Elsevier B.V.

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