February 2009 – Helen Jaques

Gallbladder removed through the vagina

February 27, 2009 No Comments

So, it’s Friday. You’re tired and don’t want to plough through a post on some complicated issue. Perfect time to revive my neglected Weird medical stories series then.

And here’s today’s bizarre case study: surgeons at Northwestern Memorial Hospital in Chicago have successfully removed a woman’s gallbladder through her vagina.

Heather Lamb, a junior high math teacher, was diagnosed with gallstones and had been experiencing severe abdominal pain for weeks. Surgeons at Northwestern decided to remove the offending gallbladder, but by using natural orifice translumenal endoscopic surgery (NOTES) rather than more-invasive laparoscopic or open surgery.

“I went home the day of surgery and felt nothing more than a little discomfort the following day,” said Ms Lamb, “I returned to work a few days later and I’m feeling great.”

The gallbladder concentrates bile produced by the liver, which is then released into the small intestine during the digestive process and helps to break down fatty food. In some people in balance of bile components gets out of whack, causing gallstones to form in the gallbladder. Gallstones can make the organ inflamed and painful and can cause bile to become trapped in the gallbladder, leading to infection. In such individuals this non-essential organ then needs to be removed.

NOTES can be used remove organs such as the gallbladder, kidney and appendix through the body’s natural orifices, such as the vagina or mouth, instead of via openings created in the skin by a surgeon’s scalpel.

Eric Hungness, a minimally invasive gastrointestinal surgeon at Northwestern Memorial Hospital who led the team that performed the surgery, says, “NOTES reduces the number of and may eliminate the need for abdominal incisions compared with traditional laparoscopic surgery, and may reduce pain and shorten recovery time for patients. This technique may also eliminate the risk of post-operative wound infections or hernias.”

In another recent example of NOTES, surgeons at Johns Hopkins University in Baltimore managed to successfully remove a healthy kidney through a donor’s vagina. Even more remarkable, the kidney was then transplanted into the donor’s niece. Transvaginal kidney removals has been performed before in order to remove cancerous or nonfunctioning kidneys that endanger a patient’s health; however, this case is the first time that a healthy organ has been removed and then transplanted.

Speaking to the BBC, Dr Robert Montgomery, chief of the transplant division at Johns Hopkins University School of Medicine, Maryland, who led the team that performed the operation, said: “Surgeons have been troubled by the need to make a relatively large incision in the patient’s abdomen after completing the nephrectomy to extract the donor kidney.

“That incision is thought to significantly add to the patient’s pain, hospitalisation and convalescence. Removing the kidney through a natural opening should hasten the patient’s recovery and provide a better cosmetic result.”

It’s quite astounding that a relatively large organ like the kidney can be teased past connective tissue and other organs to be removed through a natural orifice such as the vagina. Gross, but astounding.

Cancer, Diet and nutrition

Got breast cancer? Get to your greengrocers!

February 24, 2009 No Comments

Fruit & Veg Fresh 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.”

Mental health, Psychology

Financial altruism leads to depression

February 23, 2009 3 Comments

Lending money Do you give cash to people who aren’t your direct family or close friends, including people on the street begging for money? A new study in PLoS One suggests that such charitable behaviour will eventually lead to major depression.

Author Takeo Fujiwara found that financial altruism towards someone other than a family member or close friend was significantly associated with the onset of major depression two or three years later. Study participants who provided $10 a month or more to someone outside their close personal group were 2.6 times more likely to develop major depression than less generous individuals.

On the other hand, neither unpaid assistance – for example, helping someone other than family members or close friends with transportation or childcare – nor emotional support – comforting, listening to problems, or giving advice to anyone outside of your close personal circle – was associated with major depression. In fact, providing unpaid assistance was nonsignificantly associated with protection against depression.

The author suggests that when people give money to others, they expect some sort of ethereal reward – such as reputation or status – in return for exhibiting good behaviours. People providing emotional support immediately and directly receive emotional reward, like a sense of meaning or purpose. This disparity in compensation for altruistic behaviour might explain why those providing emotional support did not develop of MD whereas those providing financial support did.

“The differential effect on major depression between unpaid assistance [and financial support] might be due to the difference of focus, whether outside the self or not”, says Dr Fujiwara. “[P]eople might join a volunteer activity from an achievement-oriented egocentricity, rather than focusing outside the self.”

In addition, people who give money to others might feel overstretched, as financial resources are harder to come by than emotional ones, and guilty when they don’t give, both of which might contribute to major depression.

A previous study, however, has shown that providing financial support to children or grand children protects against the later onset of major depression. Better focus your financial generosity your close friends and family then.

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Takeo Fujiwara (2009) Is Altruistic Behavior Associated with Major Depression Onset? PLoS ONE 4 (2) DOI: 10.1371/journal.pone.0004557

Cancer

When NOT to screen for cancer

February 22, 2009 1 Comment

Cancer screening Annual screening for prostate cancer may not be required in many elderly men, whereas routine screening for breast cancer should probably never have been implemented, say two separate studies published this week. These studies raise questions as to whether regular screening for common cancers is really necessary and, if so, in which groups.

In the first study, due for publication in the Journal of Urology, the authors assessed 849 men aged from 40 to 92 who had been followed up for 10 years as part of the Baltimore Longitudinal Study on Aging.

During this time period, the men had undergone an average of four tests to measure prostate specific antigen (PSA) levels. PSA level in the blood is used to screen for prostate cancer: if a man has a blood PSA level of of 4.0 ng/ml or higher, it is likely that he has prostate cancer.

The authors found that in a subgroup of men aged 75 years or older who had a PSA level of below 3.o ng/ml – well within the normal range – none died of cancer and only one developed high-risk prostate cancer.

In the US and the UK, men over the age of 50 are advised to undergo annual prostate cancer screening. The findings of this study imply that routine screening may not be needed those who are over 75 and have a normal PSA level, as such individuals are unlikely to die of or experience aggressive prostate cancer during their remaining life. Even if PSA levels indicate that a man over 75 DOES have prostate cancer, it’s likely that he’ll die of something else rather than the malignancy. In such cases men could forgo risky therapy and avoid the nasty side effects that can seriously affect quality of life.

Speaking to Reuters, Dr H Ballentine Carter of Johns Hopkins University in Baltimore, one of the researchers contributing to the study said, “For the overwhelming majority of men over age 75, discontinuing PSA screening is probably a very safe thing to do”.

As for women, an analysis in the BMJ has highlighted the risks associated with mammography – including a high rate of false positives – and suggests that in many cases the risks inherent in routine screening for breast cancer outweigh the benefits.

The authors of this study argue that the NHS Cancer Screening Programmes leaflet about mammography, Breast screening: the facts, is unbalanced in its portrayal of the positives and negatives of screening and constitutes “one sided propaganda about breast screening”.

They suggest that the leaflet overplays the benefits of breast cancer screening, such as the possibility that screening leads to fewer mastectomies. Various studies indicate that the number of mastectomies actually increases when screening is introduced, they point out. The authors even dispute the statement that screening saves lives, highlighting trials showing that screening does not decrease total cancer mortality.

The authors also opine that the leaflet downplays the risks of breast cancer screening, like the possibility of being overdiagnosed, which with mammography is ten times more likely than being accurately diagnosed. “No mention is made of the major harm of screening – that is, unnecessary treatment of harmless lesions that would not have been identified without screening,” they write.

The analysis concludes that breast cancer screening is associated with less benefit and substantially more harm than previously thought and that mammography screening programmes would probably not have been initiated if the individuals who wrote the policies 20 years ago had had the evidence available today.

So should prostate cancer and breast cancer screening programmes be cut back? Doing so would avoid the consequences of false positives and would save health care providers millions of pounds in diagnostic costs.

What do you think? Would you stick to your yearly screening appointments regardless of the risk of being misdiagnosed and subjected to unneccessary treatment, just in case one day screening does catch a malignant but treatable lesion that would have otherwise been missed? Or would you rather steer clear of the hassle of screening and the stress of a false alarm?

Pharmaceutical industry

Improving communication of medication risks and benefits in direct-to-consumer ads

February 19, 2009 No Comments

A new study published in Annals of Internal Medicine has shown that adding a simple fact box to adverts for prescription drugs considerably improves consumer awareness of the risks and benefits of the medication. In this study, people who examined an advert with a drug fact box were more likely to choose the most efficacious drug than were participants who assessed an advert with an in-depth summary of the drug characteristics.

The FDA requires that direct-to-consumer adverts include a ‘brief summary’ of all the risks listed in the drug’s FDA-approved prescribing information. This summary can amount to more than a page of dense text, however, and although companies are supposed to use easy-to-understand language, the text can seem pretty impenetrable. Writing of the current system, the study authors Schwartz et al. say that “the U.S. public currently lacks accessible and accurate information about prescription drug efficacy and side effects. Instead, people are exposed to billions of dollars in marketing designed to generate enthusiasm for new products, leaving them vulnerable to persuasive marketing techniques and selective presentations of information”.

Schwartz et al. assessed whether using a ‘drug facts box’ – a 1-page round-up of a drug’s benefits and side effects, with key information on the chance of various outcomes provided in a table – improved knowledge of the risks and benefits associated with a medication and helped patients make informed treatment choices.

This study was split into two randomised trials that assessed two types of fact box: one box on how a drug treats current symptoms and one on how a drug prevents the onset of symptoms.

In the symptom drug box trial, the authors tested adverts for a fake proton-pump inhibitor (PPI) – Maxtor – and an imaginary histamine-2 (H2) blocker – Amcid. These two types of drug are used to treat symptoms of heartburn and have similar adverse effects, but clinical data show that PPIs clearly outperform H2 blockers. All 231 participants received the same ‘ad image page’ (the colorful front page) and then also received either the symptom fact box (drug box group) or a brief summary (control group).

In the prevention drug box trial, the authors used adverts for a statin – Concor – and clopidogrel – Pridclo – for prevention of future cardiovascular events. Such events are relatively rare, so the drugs have small absolute effects and are, therefore, not appropriate for many individuals. The 219 study participants were randomly assigned to receive either adverts with a brief summary or adverts with a drug box.

In the symptom drug box trial, more participants in the drug box group than in the control group were able to accurately recount the risks of the two heartburn drugs. In addition, the perceptions of individuals in the drug box group more accurately reflected the actual efficacy of the drugs. When asked which drug they would prefer to take, 68% of the drug box group chose the PPI – objectively the more effective drug – compared with 31% of the control group.

Participants in the prevention drug box trial who received the drug box adverts were more likely to understand the side effects of the two drugs. Also, most of the patients in the drug box group were able to accurately quantify the small reduction in the risk of cardiovascular events provided by the two drugs, whereas more than half of the participants in the control group overestimated the benefits of the drugs by a factor of 10 or more. Individuals in the drug box group were, therefore, more likely to conclude than the side effects associated with the drugs outweighed the small benefits provided.

The authors write: “Some may wonder whether we simply proved the obvious: one group was provided with the ‘right answers’, whereas the other was not. However, that is precisely the goal of the drug box—it provides the data needed to make informed decisions. Without these data, people can only guess, and their guesses are most likely based on the information that appears in the ads.”
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Schwartz LM et al. (2009) Communicating Drug Benefits and Harms With a Drug Facts Box: Two Randomized Trials. Ann Intern Med Early-release article: 17 February 2009

Cancer

Researchers identify new prostate cancer marker detectable in urine

February 12, 2009 1 Comment

Researchers in the US have found a new marker of the aggressiveness of prostate cancer that is detectable in the urine of men with the malignancy. Sreekumar et al. discovered that levels of sarcosine, a common amino acid found in many biological tissues, are higher in invasive prostate cancers than in benign cancers and are detectable in the urine of affected men.

Currently, prostate cancer is detected by measuring blood levels of a marker called prostate specific antigen (PSA). The diagnosis is then confirmed by taking a tissue sample (biopsy) from the prostate using a fine needle – an uncomfortable and undignified process – and examining it under a microscope.

If further trials confirm that sarcosine levels in the urine do reflect how advanced a prostate cancer is, measurement of this marker could be used as a noninvasive way to predict the aggressiveness of a cancer and thus a patient’s prognosis.

In this study, the authors recorded all the metabolites (low molecular weight molecules produced by cells) found in samples from patients with various stages of prostate cancer, ranging from benign cancer to advanced metastatic cancer. In total, 1,126 metabolites in 262 clinical samples related to prostate cancer were profiled. The authors then compared the metabolites found in the various types of tumor tissues in order to unearth ‘molecular signatures’ that distinguished the different stages of prostate cancer.

In total, 87 metabolites that distinguished prostate cancer from benign prostate tissue were found, and the levels of six of these metabolites were even higher in metastatic cancer than in any other stage of disease. Sarcosine, an N-methyl derivative of the amino acid glycine, was highly increased in metastatic samples and, importantly, was undetectable in the benign samples.

The authors then tested out what happened when they eliminated the enzyme glycine-N-methyl transferase, which is crucial for the production of sarcosine from its precursor glycine. The invasive properties of prostate cancer cells in culture were attenuated when this enzyme, and thus sarcosine, was absent. Addition of sarcosine to benign prostate epithelial cells or knockdown of the enzyme that is responsible for sarcosine degradation caused noncancerous cells to become invasive. Taken together, these findings suggest that not only is sarcosine a marker of cancer aggressiveness, it also has a role in endowing a cancer with malignant properties. Components of the sarcosine pathway may thus serve as new targets in the development of drugs that combat prostate cancer metastasis.

Lastly, the authors measured levels of sarcosine in urine specimens from individuals who had been definitively diagnosed with prostate cancer on the basis of PSA levels and prostate biopsy and compared these results with those from individuals who were biopsy negative. Levels of sarcosine were significantly higher in the urine of men with prostate cancer than in those without, confirming that measurement of sarcosine in the urine may act as an indicator of prostate cancer.

Senior study author Dr Arul Chinnaiyan told The Independent: “One of the biggest challenges we face in prostate cancer is determining if the cancer is aggressive. We end up over treating our patients because physicians don’t know which tumours will be slow-growing. With this research, we have identified a potential marker for the aggressive tumours.”

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Sreekumar A et al. (2009) Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression Nature 457 (7231): 910-914 DOI: 10.1038/nature07762

Diet and nutrition, Nephrology

Make it a DIET coke break, for the sake of your kidneys

February 11, 2009 8 Comments

Diet coke break New research published in PLoS One has shown that drinking two or more fizzy drinks a day can double a woman’s chance of developing signs of kidney disease – but only if she drinks full-sugar sodas.

David A Shoham and colleagues studied data from more than 9,000 individuals in the population-based National Health and Nutrition Examination Survey (1999–2004). They found that women who drank two or more cans of soda per day were nearly twice as likely to develop early signs of kidney disease compared with women who consumed fewer sugary soft drinks. Women who drank diet soda were not at increased risk of kidney disease, nor were men.

The rise in diabetes, obesity and kidney disease in the US has paralleled an increase in the use of high fructose corn syrup in American food. High fructose corn syrup is used in particular as a cheap way to sweeten fizzy drinks; thus, the authors investigated whether consumption of soft drinks is associated with albuminuria, a sensitive marker of early kidney damage.

In total, 11% of the sample population were found to have albumnuria, and 17% of the study group drank two or more sugary soft drinks per day. Individuals who drank more than two fizzy drinks a day were 40% more likely to have albuminuria than were participants with a more moderate intake of soda. Consumption of diet soda, however, was not associated with albuminura.

When the authors broke down their results by gender, they found that women who reported drinking two or more sodas in the previous 24 hours were 1.86 times more likely to have albuminuria than were women who drank less soda. Drinking fizzy drinks had no significant effect on the risk of albuminuria in men.

An analysis of type of soda showed that consumption of sugary non-colas was most strongly linked with albuminuria, whereas sugary cola and diet cola and non-cola drinks showed no such association.

The authors conclude that the correlation between drinking sugary sodas and albuminuria indicates that high fructose corn syrup is in part responsible for the increase in kidney disease in the US. According to the National Kidney Foundation, about 26 million American adults have chronic kidney disease.

Dr Shoham, however, has said. “I don’t think there is anything demonic about high fructose corn syrup per se … People are consuming too much sugar. The problem with high fructose corn syrup is that it contributes to over consumption. It’s cheap, it has a long shelf life and it allows you to buy a case of soda for less than $10.”
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Shoham DA et al. (2008) Sugary Soda Consumption and Albuminuria: Results from the National Health and Nutrition Examination Survey, 1999–2004 PLoS ONE 3 (10) DOI: 10.1371/journal.pone.0003431

Journals

Nature Clinical Practice journals relaunch as Nature Reviews

February 2, 2009 No Comments

The eight specialty-based Nature Clinical Practice journals, which form part of the medical publishing arm of Nature Publishing Group, are to relaunch in April 2009 as Nature Reviews.

As well as joining the hugely successful Nature Reviews portfolio, which will increase in size from seven to fifteen titles in one fell swoop, the Nature Clinical Practice journals will be given a ‘facelift’ in print and online. The previously rather austere journals are soon going to be printed in full colour, and the layout of the content has been shaken up to make the journals more eye catching and easier to navigate.

Nature Clinical Practice is a series of monthly review journals targeted at doctors and physicians. The peer-reviewed publications aim to deliver timely interpretations of key research developments, thus facilitating the translation of the latest findings into clinical practice. Doctors often don’t have time to keep abreast of developments in their field, so Nature Clinical Practice does the reading for the clinician, filtering original research published in primary journals and highlighting the most important and relevant findings.

ncp-new-names

Launched in 2004 and 2005, the Nature Clinical Practice journals cover the fields of cardiology, clinical oncology, endocrinology, gastroenterology & hepatology, nephrology, neurology, rheumatology and urology. Articles are written by experts in the field and include editorial and opinion pieces, short highlights of research from the current literature, commentaries on the application of recent research to practical patient care, comprehensive reviews, and in-depth case studies.

“Including the eight clinical journals as part of the Nature Reviews series will enable us to bring to the clinical sciences the qualities that have made the life science Nature Reviews journals so successful,” says Dr James Butcher, Publisher of the clinical Nature Reviews titles. “No other publishing company is able to offer high quality monthly review journals covering advances in medical research from bench to bedside.”

“The clinical Nature Reviews journals will retain the high quality content that practicing clinicians rely on from the Nature Clinical Practice titles,” continues Dr Butcher. “We hope that the journals will now also become indispensable resources for clinical academics working in research settings who are familiar with the look and feel of the life science Nature Reviews titles.”

I actually used to work for Nature Clinical Practice and had the chance to check out samples of the relaunch journals before I left the company. I thought the new full-colour Nature Reviews journals looked infinitely better than their somewhat dry and serious predessors, the vivid new layout really enhancing the high quality and rigorously edited content. I’m really looking forward to browsing the real thing once the first clinical Nature Reviews journals are published in April.