Viagra could help women too, but not how you think…

Metastatic Breast Cancer in Pleural FluidSince first coming on the market in 1998, the erectile dysfunction drug Viagra has improved the sex lives of countless men. Now new research has suggested that phosphodiesterase 5 (PDE5) inhibitors like Viagra could also help women – but not how you think.

Researchers in California have shown that sildenafil (Viagra) and a similar drug called vardenafil can improve the delivery of the chemotherapeutic drug Herceptin (trastuzumab) in women with breast cancer that has spread to the brain. Their studies in mice have found that PDE5 inhibitors help Herceptin cross the blood vessels of brain tumours into the heart of the cancer, thus improving the therapeutic efficacy of Herceptin for brain metastases from primary tumors.

Although only about 22,000 patients in the US are diagnosed with a primary brain tumor each year, nearly 10 times that many people develop brain tumors from cancers that began elsewhere in the body. For example, one study found that 36% of women receiving Herceptin for breast cancer developed brain metastases.

These secondary brain tumours are very hard to treat thanks to the fact that chemotherapy drugs can’t cross the walls of the tumour’s blood vessels – the blood-brain tumor barrier – and into the cancer. “Mother Nature created this barrier to protect our brains from dangerous substances, but here we need to get through the barrier to deliver the drugs, and that’s a problem,” said study author Julia Y Ljubimova, a research scientist at the Cedars-Sinai Maxine Dunitz Neurosurgical Institute in Los Angeles.  This means that drugs that can kill the primary tumour in the breast or lung aren’t effective on secondary tumours in the brain.

Ljubimova and her colleagues looked at the effects of PDE5 inhibitors on drug delivery in mice whose brains had been implanted with human lung and breast tumors. Oral administration of vardenafil to such mice doubled the uptake of Herceptin by brain tumours. Importantly, vardenafil had no effect on the uptake of Herceptin in neighbouring healthy tissue, an unfortunate effect of many chemotherapy drugs that is responsible for making cancer patients feel so awful and lose their hair.

Furthermore, combination treatment of mice with vardenafil and Herceptin increased the survival time of these mice by 20% compared with those that received Herceptin only.  This effect was only seen in mice whose brain tumours were positive for HER2, the growth factor targeted by Herceptin, and not those that were HER negative, indicating that the survival benefit was indeed due to an increase in the amount of Herceptin reaching the tumors.

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“Now that we’ve demonstrated that big molecules can cross the blood-brain tumor barrier, we’re going to continue this strategy with other big molecule drugs, such as nanomedicine drugs” said Ljubimova. “This opens a new world for brain tumor treatments.”

Hu J et al. (2010) Phosphodiesterase Type 5 Inhibitors Increase Herceptin Transport and Treatment Efficacy in Mouse Metastatic Brain Tumor Models. PLoS ONE 5 (4). DOI: 10.1371/journal.pone.0010108

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News reports on cancer don’t give the full story

NewspapersCancer stories seem to make the news on a daily basis.  For example, just today in the UK there are stories about a gene that could predispose non-smokers to lung cancer, how infertile men are at raised risk of prostate cancer, and how testing for the HPV virus during cervical screening doesn’t help pick up women who might go on to develop cervical cancer.

But it’s not just a case of “all publicity is good publicity.” Research published recently in Archives of Internal Medicine has shown that newspaper and magazine stories on cancer tend to focus on survival and aggressive treatments but steer clear of covering treatment failure, side effects of treatment, end of life care, and death.

The authors of this study looked at 436 500-word articles from top American newspapers and magazines, such as Chicago Tribune, New York Times, Newsweek, and Time. The 312 newspaper articles and 124 magazine pieces largely covered breast cancer (35.1%) and prostate cancer (14.9%), two of the most common types of cancer in the US.

Articles were more likely to focus on people who had survived or been cured of cancer than on people who had died of the disease (32.1% vs 7.6%).  In fact, those articles that covered individual patients (173 articles; 216 individuals), more than three quarters covered success stories and only a fifth told the story of someone who had died of cancer.

Few articles (13.1%) pointed out that aggressive treatments such as chemotherapy can fail or that late stage cancer can be incurable. Moreover, less than a third highlighted the side effects associated with such treatments, like pain, hair loss, and nausea.

Only two articles (0.5%) exclusively covered palliative or hospice care for when treatment options had run out, whereas more than half (57.1%) instead focused solely on aggressive treatment.

Given that one in every two men and one in every three women in the US will be diagnosed with cancer in their lifetime, half of whom will die from their cancer or related complications, this optimistic skew in media reporting of cancer is somewhat misleading.

Cancer news coverage is known to affect the beliefs and behaviours of patients; for example, media coverage of mammography screening is known to increase the use of mammography in women. As such, “The tendency of the news to report on aggressive cancer treatments and survival but not on alternatives is also noteworthy given that unrealistic information may mislead the public about the trade-offs between attempts at heroic cures and hospice care,” say the authors.

Fishman, J., Ten Have, T., & Casarett, D. (2010). Cancer and the Media: How Does the News Report on Treatment and Outcomes? Archives of Internal Medicine, 170 (6), 515-518 DOI: 10.1001/archinternmed.2010.11

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A picture is worth a thousand words: comic books for medical and patient education

Patient communicationThe BMJ has just published an interesting feature about comics in medicine – the history, the approaches, and their use in medical and patient education.

The authors Michael J Green and Kimberly R Myers call such comics “graphic pathographies”: illness narratives in graphic form. “These graphic pathographies can be helpful to patients wanting to learn more about their illness and find a community of similarly affected people,” they say. “Graphic pathographies also provide doctors with new insights into the personal experience of illness and misconceptions about disease and treatment that could affect compliance and prognosis.”

Mom's cancerThe two examples they discuss are Marisa Acocella Marchetto’s Cancer Vixen, in which Marchetto describes her experiences as “a shoe-crazy, lipstick-obsessed, wine-swilling, pasta-slurping, fashion-fanatic big-city girl cartoonist” with breast cancer, and Brain Fies’ Mom’s Cancer, which documents Fies’ mother’s metastatic lung cancer. Both provide actually quite moving and at times subtle personal accounts of illness, and in a more succinct and engaging way than the same tale in prose form.

Medikidz diabetesMedical comics are proving particularly useful in patient education, both to promote public awareness and to help patients and their families understand what to expect from a disease. Apparently, combining pictures and text enhances understanding because reading and viewing activate different information processing systems within the brain. “This combination also fosters connections between new information and existing knowledge,” say the authors, “thereby increasing recall of health information, especially among those with low literacy.”

The series Medikidz is a prime example of the latter approach. Medikidz comics provide quite complex medical information for kids about a variety of different diseases, such as osteosarcoma, scoliosis, and type 1 diabetes.

The “Medikidz” are a group of five larger-than-life superheroes who journey around Mediland, a planet shaped like the human body. These heroes battle against villainous characters representing aspects of disease. For example, Chi is the Medikidz lungs specialist whose secret power is hypnotic relaxation, whereas her nemesis is Anna Phalaxis.

Comics can also be used to educate medical students and doctors. For example, personal patient stories in comic book form could reinforce to junior doctors that fact that healing a patient entails more than treating a body. Also, as the authors point out, “In keeping with research in medical education showing that visual art improves students’ diagnostic skills, reading graphic stories may likewise enhance students’ observational and interpretive abilities.”

I find these comic fun to read, and they certainly seem a novel and creative way to communicate patients experiences and information about diseases.

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A diagnosis of prostate cancer ups the risk of fatal heart attack or suicide

Prostate cancerReceiving a diagnosis of prostate cancer is a very stressful and upsetting event, so much so that some men go on to have a fatal heart attack or kill themselves.

Two pieces of research by the same study group, one conducted in 340,000 men in the US and the other in 170,000 men from Sweden, have found that the risk of dying from a heart attack is raised by 2 to 11 times in men with a diagnosis of prostate cancer.

In addition, the risk of suicide in the first year after diagnosis in American men with prostate cancer was 40% higher than the national average and the risk in the first three months 90% higher. Astoundingly, Swedish guys were twice as likely to kill themselves in the first three months after diagnosis than men who were cancer free.

Interestingly, the US study found that the risk of suicide was only raised between 1979 and 1992, before the widespread use of screening to detect prostate cancer early.  There was no link between prostate cancer and suicide once screening, known as prostate-specific antigen (PSA) testing, was being used across the board.

So does this mean that screening for prostate cancer reduces the risk of suicide after a diagnosis? The authors think so, suggesting that early screening detects less aggressive tumors that are still treatable, thus less stress inducing.

On the other hand, the use of PSA testing has long been controversial. Many men will have small prostate tumours that never do them any harm and the test itself isn’t very reliable, so screening is associated with overdiagnosis and overtreatment.

By extension, some studies reckon that routine testing for prostate cancer causes undue stress and anxiety among patients who do not understand the implications of an abnormal result.  In fact, the Swedish study did not find any difference in suicide risk between the pre-screening era and after screening had been introduced.

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The authors aren’t sure about this difference between their two studies, admitting “The reason for this discrepancy is unclear.” However, it could potentially be caused by the large number of nonaggressive prostate cancers diagnosed during the later years in the US study or improved access to emotional support after diagnosis come the late 80s, which might have lessened despair among patients and reduced their suicide risk.

“These results add to the complex debate of pros and cons of extensive prostate-specific antigen testing and the many nonlethal prostate cancers thus detected,” say the authors.

Fall K et al. (2009) Immediate Risk for Cardiovascular Events and Suicide Following a Prostate Cancer Diagnosis: Prospective Cohort Study PLoS Medicine 6 (12). DOI: 10.1371/journal.pmed.1000197

Fang F et al. (2010). Immediate Risk of Suicide and Cardiovascular Death After a Prostate Cancer Diagnosis: Cohort Study in the United States JNCI Journal of the National Cancer Institute DOI: 10.1093/jnci/djp537

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Watching too much TV increases risk of death within the next six years

A study of nearly 9,000 Australian adults has reported that people who watched 4 hours of TV a day or more were 46% more likely to die within the next six and a half years than those who watched less than 2 hours a day.  Each one hour increase in daily television viewing increased the risk of death from any cause by 11% and death by cardiovascular disease by 18%.

Previous studies have suggested that sedentary behaviour is associated with a mortality risk.  Furthermore, surveys in the US and the UK indicate that, aside from sleeping, lounging around watching television takes up the most of our time at home – about 3 hours a day in the UK and up to 8 hours a day in the US, apparently.

This study, published in the journal Circulation, examined 8,800 adults aged 25 years or older who were in the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). All participants were interviewed at the start of the study to find out their lifestyle habits, medical history, and the amount of time they had spent watching television or videos in the previous 7 days.

About six and a half years later, on average, mortality status and cause of death for each participant was established from the Australian National Death Index.

Each one hour increase in television viewing time was associated with an 11% increase in the risk of death from any cause and an 18% increase in the likelihood of death related to cardiovascular disease. However, these relationships were attenuated once other factors like medical history and smoking habits were taken into account, but the association between TV time and death from any cause did remain important. The link between television viewing time and cancer mortality was negligible though.

Strikingly, the risk of mortality was much higher in people who watched at least 4 hours of TV a day than in those who watched less than 2 hours – the risk of death from any cause was 46% higher and the risk of death from cardiovascular disease was a whopping 80% more.

Individuals who watched 4 hours of TV a day or more were more likely to be a current or ex-smoker, have a poor diet, be overweight, or have raised blood pressure than those who watched less than 2 hours daily – that is, they seemed generally less healthy and, in theory, would be more likely to just drop dead. However, none of these factors affected the associations between television viewing and mortality.

The public health implications of this study are pretty serious – get TV addicts to cut their viewing in half and they could considerably reduce their risk of death over the next 6 years or so. As the authors say, “our findings suggest that reducing time spent watching television (and possibly other prolonged sedentary behaviors) may also be of benefit in preventing CVD and premature death.” They recommend that as well as promoting exercise, public health bodies should also “focus on reducing sitting time, particularly prolonged television viewing.”

Dunstan D et al. (2010) Television Viewing Time and Mortality: The Australian Diabetes, Obesity and Lifestyle Study (AusDiab). Circulation 121 (3): 384-391. DOI: 10.1161/CIRCULATIONAHA.109.894824

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Metal causes cancer, but iron prevents it. Courtesy of the Daily Mail.

dailymailHere’s a Friday funny for you: my friend put me onto a hilarious website called “Kill or cure“, which classifies inanimate objects on the basis of whether British newspaper the Daily Mail says they cause cancer or cure it.

Metal, according to the Daily Mail, causes cancer, but nobody panic, iron and zinc prevent it.

Nuts prevent cancer, but peanuts cause it.  Cod liver oil can give you cancer, but fish oils will protect you.  Are you still with me?!

Absolutely hilarious.

See also: the Daily Mail Oncological Ontology Project

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Aspirin in colorectal cancer – a new trick for an old dog

AspirinA new study published in JAMA this week has shown that in patients with colorectal cancer, taking an aspirin a day after diagnosis reduces the risk dying from the cancer or from any cause by at least 20%.  Taking aspirin before diagnosis, however, did not have any effect of prognosis.

It has been known for a few years that regular aspirin use can reduce the risk of developing colorectal cancer.  This drug isn’t a good idea as a preventive strategy though as it is associated with gastrointestinal irritation and bleeding – pretty serious side effects.  What this new study shows is that when it comes to colorectal cancer, aspirin might be just as effective and more practical as a treatment for people who already have the disease.

In this study, the authors first followed a whopping 170,000 health professionals for 20 years.  The 1279 men and women who developed colorectal cancer then completed a survey on aspirin use every two years for a further 7-10 years.

The majority of people who used aspirin reported taking the drug as an analgesic, mostly for headache or arthritis and other musculoskeletal pain.  A notable proportion, men in particular, took aspirin for cardiovascular disease prevention, which this handy little drug has also proved effective at.

Compared with participants who did not use aspirin, people who regularly used aspirin either after diagnosis only or both before and after diagnosis were 29% less likely to die from colorectal cancer and 21% less likely to die from any cause.  On the other hand, aspirin had no effect on mortality risks in people who took aspirin before cancer diagnosis only or both before and after diagnosis.

When the analysis was restricted to people who started taking aspirin after diagnosis only,  the risks of cancer-specific mortality and overall mortality were 47% and 32% lower than in those who didn’t take aspirin at all.  Conversely, there was no benefit seen specifically in the group that took aspirin before diagnosis and continued once they knew they had colorectal cancer.

The effect of aspirin in colorectal cancer was particularly strong in patients whose primary tumors overexpressed the enzyme cyclooxygenase 2 (COX-2), which crops up in about 80% of colorectal cancers, suggesting that aspirin might be an effective treatment in the majority of people with this type of cancer.  The amount of aspirin consumed also altered the effect – the mortality risk was slightly lower in people who took 6 or more tablets a week than in those who took 0.5 to five a week.

In an accompanying editorial, Alfred Neugut at Columbia University states that “aspirin may become standard adjuvant therapy in the management of colorectal cancer.” This treatment has the added advantage of being highly specific to are therefore only useful in patients with tumors that overexpress COX-2, so that “this potential future treatment comes with its own ready-made predictive biomarker.”

Chan AT, Ogino S, Fuchs CS (2009) Aspirin Use and Survival After Diagnosis of Colorectal Cancer JAMA 302 (6): 649-658 LINK

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Cancer survivor detained by US immigration because treatment eradicated fingerprints

fingerprintA 62-year-old cancer survivor was recently temporarily denied entry into the US because the treatment he had been receiving had wiped out his fingerprints.

The patient, Mr S, had been taking the chemotherapy drug capecitabine for three years to prevent recurrence of his nasopharyngeal cancer following successful treatment of the disease with another chemotherapy regimen.

Capecitabine can cause inflammation, peeling, bleeding and blistering of the palms of the hands and soles of the feet, a side effect known as plantar-palmar syndrome.  Interestingly, survival is significantly better in patients on capecitabine who experience this severe plantar-palmar syndrome.

The case report of Mr S, published in Annals of Oncology, states that the patient had grade 2 plantar-palmar syndrome that did not affect his daily activities and function. He was not aware that he had lost his fingerprints when he set off from Singapore to visit relatives in the US.

According to the case report, Mr S “was detained at the airport customs for four hours because the immigration officers could not detect his fingerprints. He was allowed to enter after the custom officers were satisfied that he was not a security threat”.

The patient’s oncologist Dr Eng-Huat Tan, senior consultant at Singapore’s National Cancer Center, advises that all patients who are receiving capecitabine carry a doctor’s letter with them when they travel, as doctors are not sure which patients on the drug will lose their fingerprints or when in the course of treatment this will occur.

“Patients taking long-term capecitabine may have problems with regards to fingerprint identification when they enter United States’ ports or other countries that require fingerprint identification and should be warned about this”, writes Dr Tan. “There may be a growing number of such patients as Mr S who may benefit from maintenance capecitabine for disseminated malignancy. These patients should prepare adequately before travelling to avert the inconvenience that Mr S was put through.”

International airports in the US have been fingerprinting foreign visitors since 2004 under the US-Visit (US Visitor and Immigrant Status Indicator Technology) security system. At least two index fingerprint images are taken from all foreign visitors, including those from countries in the visa waiver scheme such as the UK, which are matched with millions of records to detect whether the visitor is attempting to use fradulent identification. These fingerprints are also matched to a list of known or suspected terrorists, criminals and immigration violators.

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Religious people are just as reluctant to die as the rest of us

christYou’d think people with strong religious beliefs – which generally include belief in an afterlife – would be less perturbed about slipping of this mortal coil than the rest of us.

A new study published in the Journal of the American Medical Association, however, has found that cancer patients who rely on their religion for comfort during their final days are in fact almost three times more likely to use life-prolonging treatments than are less religious patients.

The authors of this study first used a questionnaire to assess ‘positive religious coping’ in 345 patients with advanced cancer.  Religious coping – for example, prayer, meditation and religious study – can provide terminally ill patients with a sense of meaning, comfort and control during their last days. “Positive religious coping has been widely associated with improved psychological adjustment to stressors including serious illness”, the authors write.

The majority of patients (78.8%) reported that religion helped them cope ‘to a moderate extent’ or more, with a third saying that religion was the most important thing that kept them going. In addition, more than 50% of participants endorsed engaging in prayer, meditation, or religious study at least once a day.

Patients were then monitored until their death on average 122 days after this initial evaluation and their use of intensive life-prolonging care, such as mechanical ventilation or cardiopulmonary resuscitation, during their last week of life was recorded.

Patients who had a high level of positive religious coping were nearly three times more likely to use intensive life-prolonging end-of-life care treatments than were individuals with a low level of religious coping. This disparity persisted even once the authors had taken into account other factors that might affect end-of-life treatment decisions, such as terminal illness acknowledgment and preference for heroics.

Religious patients were also more likely to want physicians to do everything possible to keep them alive and less likely to make plans for the end of their life, such as instigating a do-not-resuscitate order or a living will.

“[I]ntrinsic to positive religious coping is the idea of collaborating with God to overcome illness and positive transformation through suffering. Sensing a religious purpose to suffering may enable patients to endure more invasive and painful therapy at the end of life”, say the authors.  Highly religious patients “may choose aggressive therapies because they believe that God could use the therapy to provide divine healing, or they hope for a miraculous cure while intensive medical care prolongs life.

So the authors’ take seems to be that religious people use their faith to help them endure a painful treatment in the hope that the therapy, or God, might save their life, whereas less religious people lack such stoicism.  Frankly, I’m quite surprised that religious people aren’t more ready to accept death when it comes, as they’re guaranteed a front-row seat in heaven.  The rest of us, on the other hand, are likely to spend our last days consumed by existential angst and would surely want to prolong the final reckoning for as long as possible.

Phelps AC et al. (2009) Religious Coping and Use of Intensive Life-Prolonging Care Near Death in Patients With Advanced Cancer JAMA 301 (11): 1140-1147 Abstract online

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Got breast cancer? Get to your greengrocers!

Fruit & VegFresh fruit and vegetables can inhibit the growth of breast cancer tumors and reduce the risk of death in women who already have breast cancer, say two new studies.

The first study is one of several on the effects of fresh apple extracts in rats.  Whole apple extracts have strong antiproliferative and antioxidant activities, thought to be a result of the combination of phytochemicals in the fruit.

This study found that giving rats with mammary tumors a dosage of apple extracts equivalent to one apple a day in humans seriously curtailed the likelihood of tumor growth.  In total, only 57% of rats fed low doses of apple extracts experienced rapid tumor growth over the 24-week study compared with 81% of control animals, who received no apple extracts whatsoever.

Strikingly, only 23% of the rats fed high doses of apple extracts showed signs of tumor proliferation. Scaled up, a human would need to consume six apples a day to benefit from this protective effect.

Rui Hai Liu, Cornell associate professor of food science and one of the study’s authors, said, “We not only observed that the treated animals had fewer tumors, but the tumors were smaller, less malignant and grew more slowly compared with the tumors in the untreated rats.”

A second study of 1,901 women with early-stage breast cancer found that a healthy diet of fruit, vegetables, whole grains, and poultry reduced the risk of death from any cause.

The risk of death in women who stuck rigidly to a ‘prudent’ diet was almost 50% lower than that in women who paid less attention to what they ate.  On the other hand, the risk of death in women who ate a Western diet comprising a high intake of red and processed meats and refined grains was much higher than in less unhealthy women.  These observations were generally not modified by physical activity, being overweight, or smoking.

Interestingly, neither dietary pattern was associated with risk of breast cancer recurrence or death from breast cancer.

The authors conclude that “women diagnosed with early-stage breast cancer might improve overall prognosis and survival by adopting more healthful dietary patterns.”

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