Bladder cancer and arsenic through drinking water: A systematic review of epidemiologic evidence

Exposure to inorganic arsenic (As) through drinking water is a major international public health issue. We carried out a systematic review of the existing literature examining the association between the risk of bladder cancer in humans and exposure to arsenic through drinking water.We searched electronic databases for studies published from January 2000 up to April 2013. Eight ecological studies, six case-control studies, four cohort studies and two meta-analyses were identified. The vast majority of the studies were carried out in areas with high arsenic concentrations in drinking water such as southwestern and northeastern Taiwan, Pakistan, Bangladesh, Argentina (Cordoba Province), USA (southeastern Michigan, Florida, Idaho) and Chile. Most of the studies reported higher risks of bladder cancer incidence or mortality in areas with high arsenic concentrations in drinking water compared to the general population or a low arsenic exposed control group. The quality assessment showed that among the studies identified, arsenic exposure was assessed at the individual level only in half of them and only three assessed exposure using a biomarker. Further, five out of eight ecological studies presented results with adjustment for potential confounders except for age; all cohort and case-control studies presented results with adjustment for cigarette smoking status in the analysis. The majority of the studies with varying study designs carried out in different areas provided evidence of statistically siginificant increases in bladder cancer risk at high concentrations of arsenic (>50 μg L−1). Assessing bladder cancer risk at lower exposure concentrations requires further investigation

Highlights from the 24th conference on retroviruses and opportunistic infections, 13-16 February 2017, Seattle, Washington, USA

From the 13th to 16th February 2017, researchers from around the world convened for the 24th annual Conference on Retroviruses and Opportunistic Infections (CROI) at the Washington State Convention Center in Seattle, Washington. The conference was organised by the International Antiviral Society-USA (IAS-USA) in partnership with the CROI Foundation. The conference included over 1000 oral and poster presentations of peer-reviewed original research as well as lectures and symposia featuring insights from leading basic, translational and clinical researchers. Highlighted here are key data presented at the conference

Online Advertising for Cancer Prevention: Google Ads and Tanning Beds

Google receives more than 3.5 billion Internet searches daily, and the advertisements on their results pages may provide a unique opportunity to transmit targeted public health information to a large audience. Skin cancer is more common than all other cancers combined, and indoor tanning is a preventable risk factor that accounts for more than 450 000 new malignant neoplasms each year. Tanning bed use remains common, with 1 in 5 adolescents and more than half of college students exposed. Awareness of the dangers of tanning beds is one of the factors that can lead to behavior change. The goals of this study were to examine the volume of tanning bed–related searches on Google and pilot the use of Google’s advertising service for dissemination of skin cancer prevention messages to users entering searches related to tanning beds

Clinical use of HIV integrase inhibitors : a systematic review and meta-analysis

Background: Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. Methods: MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. Results: 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59-0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11-0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89-2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. Conclusion: In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment

Solitary fibrous tumour of the genitourinary tract: a clinicopathological study of 11 cases and their association with the NAB2-STAT6 fusion gene

Aims To characterise clinicopathological features and clinical outcomes of the genitourinary tract solitary fibrous tumours, incorporating NAB2-STAT6 gene fusion status. Methods The presence of the molecular hallmark NAB2-STAT6 gene fusion and for the defining fusion partner product STAT6 was assessed in 11 cases of the genitourinary tract solitary fibrous tumours. NAB2-STAT6 gene fusion analysis was performed using a break-apart fluorescence in situ hybridisation (FISH) probe using a probe cocktail with Bacterial artificial chromosome (BAC) clones for STAT6 and NAB2. Results Eleven solitary fibrous tumours were diagnosed in eight male patients and three female patients with a mean age of 46 years (range: 11–64 years). Four of the tumours had malignant histological features, and three were considered moderate risk for metastasis. With a mean follow-up time of 61 months, 1 recurred locally and 2 presented at distant metastatic sites. Using a break-apart FISH probe cocktail, we found the NAB2-STAT6 gene fusion and nuclear STAT6 expression in 58% and 91% of cases, respectively. However, the NAB2-STAT6 fusion status was not correlated with STAT6 expression or useful in discriminating between malignant histological features or subsequent clinical outcomes in the genitourinary solitary fibrous tumours. Conclusions A subset of solitary fibrous tumours of the genitourinary tract behaved aggressively. Using a break-apart FISH probe cocktail, we found the NAB2-STAT6 gene fusion in 64% of cases. However, the NAB2-STAT6 fusion status was not correlated with STAT6 expression or useful in discriminating between low-risk or high-risk tumours and subsequent clinical outcomes

LKB1 as the ghostwriter of crypt history

Familial cancer syndromes present rare insights into malignant tumor development. The molecular background of polyp formation and the cancer prone state in Peutz-Jeghers syndrome remain enigmatic to this day. Previously, we proposed that Peutz-Jeghers polyps are not pre-malignant lesions, but an epiphenomenon to the malignant condition. However, Peutz-Jeghers polyp formation and the cancer-prone state must both be accounted for by the same molecular mechanism. Our contribution focuses on the histopathology of the characteristic Peutz-Jeghers polyp and recent research on stem cell dynamics and how these concepts relate to Peutz-Jeghers polyposis. We discuss a protracted clonal evolution scenario in Peutz-Jeghers syndrome due to a germline LKB1 mutation. Peutz-Jeghers polyp formation and malignant transformation are separately mediated through the same molecular mechanism played out on different timescales. Thus, a single mechanism accounts for the development of benign Peutz-Jeghers polyps and for malignant transformation in Peutz-Jeghers syndrome

Modifiable risk factors for RA: prevention, better than cure?

Objective. To perform a meta-synthesis of the evidence for modifiable lifestyle risk factors for inflammatory polyarthritis (IP) and RA