Nephron-Sparing Surgery Strategy: The Current Standard for the Treatment of Localised Renal Cell Carcinoma

In the past few years, there has been a trend towards nephron-sparing surgery (NSS) strategies in renal cell carcinoma (RCC). The previous standard treatment—radical nephrectomy (RN)—has been abandoned, because a number of studies have shown similar oncologic outcomes after NSS for localised RCCs at least up to 7 cm. RN is recommended only in patients with locally advanced tumour growth; those who have an unfavourable tumour location; or for other clinical reasons, such as general health.


The major advantage of NSS is the preservation of renal function.

Evidence acquisition

Medical literature was retrieved from PubMed.

Evidence synthesis

Already, one-fourth of patients in the current RCC population having tumours <4 cm in size have significantly impaired renal function diagnostic for stage 3 chronic kidney disease. Patients who have and those at risk for impaired renal function of the contralateral kidney have a higher risk for cardiovascular events and decreased overall mortality after RN.


In general, NSS is currently advocated for patients with pT1 RCCs whenever technically feasible. This recommendation is based on the evidence that preserving kidney function in the long term results in reduced frequency of cardiovascular events and decreased overall mortality than after RN. Compared with RN, NSS has slightly higher complication rates but is a safe technique offering similar oncologic results.

Take Home Message

Current wisdom is that preserving kidney function results in reduced long-term frequency of cardiovascular events after renal surgery. Nephron-sparing surgery, which offers similar oncologic results to radical nephrectomy, is advocated in the treatment of renal cell carcinoma whenever possible.

source: European journal supplement


Incentives for promoting smoking cessation: what we still do not know

thumbnail image: Incentives for promoting smoking cessation: what we still do not know

In a newly updated Cochrane Review, Cahill and Perera summarise the effectiveness of incentives for smoking cessation.[1] Their disappointing conclusion is that while there is some evidence that incentives work in the short term, the effects generally dissipate, and there is still insufficient evidence to recommend their adoption into routine practice. Much therefore remains to be discovered, but what are the particular questions that this review highlights?

Behaviour change has been divided into ‘simple’ (single actions at a point in time) and ‘complex’ (requiring effort over a sustained period).[2] Adherence to medication is an example of a simple behaviour change. A systematic review in the BMJ, which assessed financial incentives to motivate adherence to medical instructions, identified 11 randomised controlled trials.[3] The incentives ranged from USD 5 to about USD 1,000. Of the 11 studies included in the review, 10 demonstrated a positive effect. The studies incentivised several types of interventions, such as immunisation, engaging with antihypertensive treatment, attending postpartum appointments, completing cocaine dependency treatment, and dental care for children.

Complex behaviour change requires both sustained effort and typically the adoption of multiple strategies to achieve change. Like smoking cessation, weight loss to reduce obesity requires complex behaviour change. A systematic review of trials of incentives for weight loss found that larger incentives seemed more effective but that the effectiveness of interventions seemed to decline when the incentive was withdrawn,[4] paralleling the data in the Cahill and Perera review.[1] Might we conclude that incentives are effective for simple but not complex behaviour change?

This conclusion may seem at odds with the strong evidence for the efficacy of incentives for the management of drug misuse.[5] While there is clear evidence that incentives increase adoption of simple behaviours, such as immunisations against tuberculosis or hepatitis, there is also evidence for improved abstinence from problem drug use, clearly a complex behavioural change. Although ceasing to use illicit drugs does require complex change, some actions are simple. Deciding to engage in a treatment programme in the first place is simple, and attending regularly for supervised dispensing of methadone, for example, is also a simple behaviour. These behaviours are part of the set of behaviours that have been effectively rewarded in previous trials of incentives in drug misuse. The shining exception to the rather negative findings in the Cochrane Review of incentives for smoking cessation is the trial by Volpp and colleagues.[6] In this study, participants gained rewards for attending a smoking cessation clinic as well as for validated abstinence and, as a result, nearly three times as many in the intervention group attended as in the control group. The intervention also increased the rate at which participants achieved abstinence at short-term follow-up. Although a somewhat lower proportion of people who achieved early abstinence returned to smoking in the intervention group than the control group, it seems the main effect was inducing two simple behavioural changes. The first prompted people to decide to quit smoking and the second prompted people to use evidence-based treatment.

Cahill and Perera also hint that other studies support the conclusion that incentives seem to work by drawing people into a cessation attempt. This is valuable because, while most smokers regret smoking and want to stop,[7] only a minority of these take action and try to quit in any one year. Other Cochrane Reviews testify to the effectiveness of both behavioural support and medication in enhancing smoking cessation (e.g. Stead and Lancaster[8] and Stead et al.[9]), but these aids are infrequently used by people to support their cessation attempt. In the UK, for example, there is a widespread network of (free) cessation clinics dispensing (reimbursed) medication to support cessation, and their availability is advertised and promoted by healthcare professionals. Despite this, fewer than 10% of quitters use these clinics.[10] It might be helpful for future studies to consider specific behaviours that they are trying to reward rather than cessation generally, perhaps focusing early in the process of quitting. Volpp and colleagues paid study participants up to USD 750 each.[6] Perhaps the incentives required for simple behaviour change could be less than this. Simple behaviour changes may be sufficient to increase the proportion of quitters who attempt to stop or who use aids to cessation, either of which will increase the number of long-term abstainers. Even interventions of marginal effectiveness in smoking cessation are cost-effective because the benefits of cessation are so great,[11] so this is an important area where further research would be useful.

Many people are sceptical about financial incentives to support behaviour change. One factor that might reinforce this is obvious ‘gaming’ the system to gain incentives. People who do not smoke may claim to smoke in order to have the chance to ‘stop’ smoking and claim a reward. Unlike in opioid addiction, smokers do not typically face confirmatory tests to show that they are smokers. Cahill and Perera report few studies that addressed this issue. The studies did, however, more commonly use biochemical tests to confirm that when participants reported that they were abstinent, they were in fact abstinent. One problem with these tests is that they can confirm abstinence over the previous few hours only, in the case of carbon monoxide, or days only, in the case of cotinine.[12] Furthermore, because participants had to make appointments to declare and prove their non-smoking status, participants were effectively warned of the testing, and this leaves the door open for gaming. Only surprising smokers with tests can really appease sceptics, and such data are not yet available.

Smoking in pregnancy is a relatively intractable public health problem. A Cochrane Review of smoking cessation in pregnancy found that many of the interventions that are known to be effective in adult smokers are not known to be effective in pregnant women.[13] Financial incentives seemed the most effective intervention, increasing abstinence over three-fold. However, the outcomes of these trials were abstinence for the previous seven days, so the data are preliminary. Many women who smoke in pregnancy are among the most disadvantaged in society. If incentives have a place in smoking cessation, it is perhaps this group who might be seen as the most deserving. Both this review and the Cahill and Perera review show us the potential value of incentives. They appear to work sometimes for some smokers. Understanding how they work, whether the benefits are sustained, and that their effects are not due to gaming the system, is a public health priority.

source: cochrane library

Benefits of Olmesartan Outweigh Potential Risk for Cardiovascular Death

The benefits of olmesartan (Benicar) “continue to outweigh its potential risks when used for the treatment of patients with high blood pressure according to the drug label,” the FDA announced on Thursday.

The agency began a safety review of the angiotensin-receptor blocker in June 2010 after two studies showed a higher rate of cardiovascular death among patients taking olmesartan, compared with those taking placebo; the trials aimed to show whether olmesartan would slow progression of kidney disease in patients with diabetes. In its update on Thursday, the FDA cautions against using olmesartan to delay or prevent microalbuminuria in patients with diabetes.

The agency advises that clinicians “follow the recommendations in the drug label” when prescribing the drug. The manufacturer has agreed to conduct further studies on olmesartan’s cardiovascular risk profile.

Source: FDA MedWatch alert

More Cancer Cases in Young Adults Under Treatment for Crohn’s, Ulcerative Colitis

The FDA says it continues to receive reports of hepatosplenic T-cell lymphoma in patients receiving treatment with tumor necrosis-factor (TNF) blockers, azathioprine, or mercaptopurine.

The agency lists a total of 43 cases of the aggressive cancer, mostly among young people, but with some among older adults. Most had been under treatment for Crohn’s disease or ulcerative colitis with a combination of immunosuppressants, but cases were reported in patients taking azathioprine or mercaptopurine alone.

Two years ago, the FDA added a boxed warning to TNF blockers on the risk for cancer in children and adolescents using the drugs. TNF blockers include Remicade (infliximab), Enbrel (etanercept), Humira (adalimumab), Cimzia (certolizumab pegol) and Simponi (golimumab).

The agency says “risks and benefits of using TNF blockers, azathioprine, and/or mercaptopurine should be carefully weighed when prescribing these drugs to children and young adults, especially for the treatment of Crohn’s disease and ulcerative colitis.”

Source:FDA MedWatch alert

Treating High Blood Pressure May Delay Alzheimer’s

Treatment Reduced Risk of Progression to Alzheimer’s by 39% in Study.
senior woman having bp checked

Treating high blood pressure and other so-called vascular risk factors in people who have mild cognitive impairment may reduce their risk of progressing to Alzheimer’s disease, according to a new study.

“Recent animal studies suggest that vascular risk factors play roles in the development of Alzheimer’s disease,” says researcher Yan-Jiang Wang, MD, PhD, a professor of neurology at Third Military Medical University in Chongqing, China.

“But it still remains unclear whether vascular risk factors cause Alzheimer’s disease in humans,” he tells WebMD in an email. “Our study provides important evidence in humans which supports the idea that vascular risk factors play a critical role in the development of Alzheimer’s disease.”

Reducing the Risk of Alzheimer’s Disease: Study Details

The researchers enrolled 837 men and women, all aged 55 and older.

All had a condition known as mild cognitive impairment (MCI), which is a mental condition less severe than dementia, with symptoms such as forgetting recent events, difficulty multitasking, and taking longer to perform mental tasks. MCI increases the risk of progressing to Alzheimer’s disease.

At the start of the study, 414 had one or more vascular risk factors, such as high blood pressure, high cholesterol, or diabetes.

Wang’s team evaluated the participants each year for five years with standard tests of cognitive function and their ability to do daily activities.

After some dropped out, 650 completed the follow-up. During that time, 298 progressed to Alzheimer’s, while the others remained with mild cognitive impairment. Participants who had vascular risk factors were twice as likely to develop Alzheimer’s over the five-year follow-up as those who did not have any of the vascular risk factors.

However, study participants who received treatment for all their vascular risk factors were 39% less likely to get Alzheimer’s disease over the follow-up period than those who got no treatment.

Even treating some of the risk factors helped. It reduced the risk of progression by 26%.

The study is strictly observational, the researchers say. Therefore, it cannot prove cause and effect. However, they write, ”active intervention for vascular risk factors might reduce progression in MCI to Alzheimer’s disease dementia.”

Although the link is not proven, Wang tells WebMD ”there would be no downside to treating the vascular risk factors.”

Vascular Risk Factors and Delaying Alzheimer’s: Explaining the Link

Researchers say it’s unclear why the risk factors appear to speed the progression from MCI to Alzheimer’s disease.

Some of the vascular risk factors may directly affect the metabolism of a protein known as beta-amyloid. The protein has been linked with Alzheimer’s disease. When it accumulates in the brain, it is believed to disrupt cells and cellular functioning.

That may indicate that vascular risk factors play a pivotal or causal role in Alzheimer’s, the researchers write.

Delaying Alzheimer’s Disease: Perspective

The new study findings offer a great message for people, says William Thies, PhD, chief medical and scientific officer for the Alzheimer’s Association. “Get your cardiovascular risk factors checked, and get treatment if you need it,” he says.”The benefits for you may be far more than [preventing] vascular disease.”

He reviewed the study for WebMD but was not involved in the research.

He adds, however, that the study is simply observational, not a clinical trial. So it does not prove that treating vascular risks will definitely delay the progression to Alzheimer’s.

source: webMD

FDA Explains Why It Approved the Higher Dose of Dabigatran

The RE-LY study that led to the FDA’s approval of dabigatran compared two different regimens of the drug — 110 or 150 mg twice daily — against warfarin. Both were noninferior to warfarin, so why didn’t the FDA approve both, giving clinicians and patients a choice?

Writing in the New England Journal of Medicine, FDA scientists explain that the 110-mg dose, while superior to both warfarin and the 150-mg dose in reducing risk for major bleeding, carried a greater risk for stroke. The higher bleeding risk with the 150-mg dose, in the FDA’s judgment, was acceptable, given “that the irreversible effects of strokes and systemic emboli have greater clinical significance than nonfatal bleeding.”

In addition, patients who suffered a bleeding event while on the higher dose were unlikely to suffer another, even when they continued taking the medication at the higher dose.

Source: NEJM perspective

Value of GFR and Albuminuria in Predicting Cardiovascular Outcomes

Glomerular filtration rate and albuminuria did not add value to traditional risk factors.

Multiple studies have shown that albuminuria and low estimated glomerular filtration rate (eGFR) predict development of adverse cardiovascular outcomes. Using data from two large studies — ONTARGET) and TRANSCEND) — involving more than 27,000 patients (age, >55) who had vascular disease or diabetes with symptoms of end-organ involvement, researchers evaluated whether eGFR and albuminuria added predictive power beyond that of traditional risk factors.

Mean follow-up was 4.6 years. Low eGFR and elevated urine albumin–creatinine ratios were associated with excess risk for cardiovascular-related death, myocardial infarction, stroke, or hospitalization for heart failure. However, after controlling for traditional cardiovascular risk factors (i.e., age, sex, diabetes, cardiovascular disease, smoking status, blood glucose and LDL cholesterol levels), addition of eGFR or urine albumin–creatinine ratio failed to improve classification of individuals who did or did not experience adverse cardiovascular outcomes during follow-up.

Comment: In this study, eGFR and albuminuria failed to significantly improve risk stratification beyond that of traditional cardiovascular risk factors. Of note, the study was conducted among a high-risk population, and the findings might not apply to lower-risk individuals.


Source:Journal Watch General Medicine