Breast cancer patients with lymphedema in their upper arm experienced reduced fluid in the swollen arm by up to 39 percent after undergoing a super-microsurgical technique known as lymphaticovenular bypass, report researchers at The University of Texas M. D. Anderson Cancer Center.

The results from the prospective analysis, presented at the 88th Annual Meeting of the American Association of Plastic Surgeons, suggest another option for breast cancer patients considering ways to manage lymphedema, a common and debilitating condition following surgery and/or radiation therapy for breast cancer.

Lymphedema results when the lymph nodes are removed or blocked due to treatment and lymph fluid accumulates causing chronic swelling in the upper arm. Currently, there is no cure or preventive measure for lymphedema and it is difficult to manage; the use of compression bandages, massage and other forms of lymphatic therapy are commonly recommended options for patients. According to the National Cancer Institute, 25 to 30 percent of women who have breast cancer surgery with lymph node removal and radiation therapy develop lymphedema.

Researchers evaluated 20 breast cancer patients with stage II and III treatment-related lymphedema of the upper arm who underwent a lymphaticovenular bypass at M. D. Anderson from December 2005 to September 2008. Due to lymphedema, the patients' affected arm was an average of 34 percent larger compared to the unaffected arm prior to the surgery. Of these 20 patients, 19 reported initial significant clinical improvement following the procedure. In those patients with postoperative volumetric analysis measurements, total mean reduction in the volume differential at one month was 29 percent, at three months 33 percent, at six months 39 percent and 25 percent at one year.

"Patients often resort to lymphatic therapy because other options brought forward to reduce lymphedema haven't proved effective," said lead author on the study David W. Chang, M.D., professor in the Department of Plastic Surgery and Director of the Plastic Surgery Clinic at M. D. Anderson. "Surgical techniques, in particular, have been limited and therefore have been met with skepticism by surgeons, making it extremely important to determine which new techniques promise to bring real benefits to patients."

In lymphaticovenular bypass surgery, surgeons use tiny microsurgical tools to make two to three small incisions measuring an inch or less in the patient's arm. Lymphatic fluid is then redirected to microscopic vessels - approximately 0.3 - 0.8 millimeters in diameter - to promote drainage and alleviate lymphedema. The procedure is minimally invasive and is generally completed in less than four hours under general anesthesia, allowing patients to return home from the hospital within 24 hours. M. D. Anderson is among a few institutions in the United States to offer this technically complex surgery.

"Lymphedema is like a massive traffic jam with no exit," Chang said. "This procedure does a lot to help relieve lymphedema by giving the fluid a way out. While it does not totally eliminate the condition, there is very little downside for the patient and we may see significant improvement in its severity."

Chang notes that while most effective when completed in earlier stages before the affected arm is fibrotic, almost any breast cancer patient suffering from lymphedema stage I, II or III is a candidate. Though breast cancer was the focus of this study, the surgery can also be performed on patients who have lymphedema in the leg resulting from cancers involving pelvic regions.

Cancer treatment is not the only cause of lymphedema. Primary lymphedema can develop from developmental causes at birth, the onset of puberty or in adulthood. Secondary lymphedema can develop as a result of surgery, radiation, infection or trauma. In developing countries, a form of lymphedema caused by a parasite called Filariasis affects as many as 200 million people worldwide. "As we begin to refine our technique and learn more about the efficacy of this surgery, we have the potential to impact a large number of people," Chang said.

Long-term follow-up with patients who have received lymphaticovenular bypass surgery is necessary to determine if the procedure continues to promote drainage after one year. Chang and his team of surgeons at M. D. Anderson believe that the fluid volume will keep decreasing over time and suggest that the surgery could possibly be used as a preventive measure for lymphedema in the future. "Working toward a definitive technique to cure this encumbering side effect of cancer and improve a patient's quality of life as a cancer survivor is a priority for those of us in this field."

For patients with end-stage renal disease (ESRD), receiving care from a nephrologist in the months before starting dialysis reduces the risk of death during the first year on dialysis, reports a study in the May 2009 issue of the Journal of the American Society of Nephrology (JASN). The study also shows geographic "clusters" where pre-dialysis care for patients with advanced chronic kidney disease (CKD) is not optimal. "Assistance to improve pre-dialysis care might be profitably targeted to specific treatment centers and the health care systems they serve," comments William McClellan, MD (Emory University School of Medicine, Atlanta, GA).

Dr. McClellan and colleagues analyzed data on more than 30,000 patients starting dialysis in five of the 18 US ESRD Network regions. The researchers evaluated the quality of the patients' medical care in the months before their CKD progressed to ESRD, and how that affected the patients' outcomes on dialysis.

Just over half of the patients received at least six months of pre-dialysis care from a nephrologist, as recommended by current guidelines. For these patients, the chances of surviving the first year on dialysis were about 50 percent higher than for patients who did not receive at least six months of nephrologist care. Survival rates were higher at dialysis centers where more patients received recommended care.

The researchers also unexpectedly discovered that dialysis centers with the lowest rates of recommended pre-dialysis care tended to be "clustered geographically." For example, there was a "significant circular cluster" of low pre-dialysis care centers located in Alabama and Mississippi.

Although the reasons for the geographic variations in care are unclear, the results identify specific regions that might benefit from efforts to improve care for advanced CKD patients. "The Centers for Medicare & Medicaid Services are currently conducting a pilot quality improvement initiative in ten states to determine the feasibility of such efforts," says Dr. McClellan.

Cambridge-based researchers provide new evidence that the human brain lives "on the edge of chaos", at a critical transition point between randomness and order. The study, published March 20 in the open-access journal PLoS Computational Biology, provides experimental data on an idea previously fraught with theoretical speculation.

Self-organized criticality (where systems spontaneously organize themselves to operate at a critical point between order and randomness), can emerge from complex interactions in many different physical systems, including avalanches, forest fires, earthquakes, and heartbeat rhythms. According to this study, conducted by a team from the University of Cambridge, the Medical Research Council Cognition & Brain Sciences Unit, and the GlaxoSmithKline Clinical Unit Cambridge, the dynamics of human brain networks have something important in common with some superficially very different systems in nature. Computational networks showing these characteristics have also been shown to have optimal memory (data storage) and information-processing capacity. In particular, critical systems are able to respond very rapidly and extensively to minor changes in their inputs.

"Due to these characteristics, self-organized criticality is intuitively attractive as a model for brain functions such as perception and action, because it would allow us to switch quickly between mental states in order to respond to changing environmental conditions," says co-author Manfred Kitzbichler.

The researchers used state-of-the-art brain imaging techniques to measure dynamic changes in the synchronization of activity between different regions of the functional network in the human brain. Their results suggest that the brain operates in a self-organized critical state. To support this conclusion, they also investigated the synchronization of activity in computational models, and demonstrated that the dynamic profile they had found in the brain was exactly reflected in the models. Collectively, these results amount to strong evidence in favour of the idea that human brain dynamics exist at a critical point on the edge of chaos.

UK scientists found that a type of angiogenesis inhibitor used to treat cancer can actually encourage rather than stop tumour growth when given at low doses.

The researchers who carried out the study are from the The Institute of Cancer, Queen Mary, University of London, the Institute of Cancer Research (ICR), a college of the University of London, and the Beatson Institute for Cancer Research, Glasgow and they published their findings in the 22 March online issue of Nature Medicine.

Angiogenesis inhibitors are designed to stop tumours growing by cutting off their blood supply. They work by changing the way molecules that control cell behaviour send signals to each other, a very complex process.

In this study, lead investigator Dr Kairbaan Hodivala-Dilke of The Institute of Cancer and colleagues focused on an experimental angiogenesis inhibitor called cilengitide that has not yet been licensed for patients.

This type of angiogenesis inhibitor targets integrins, cell receptors that help to regulate how cells stick to other cells and to the cell-matrix (tissue that is not part of a cell) and also play a role in processing signals that pass between cells and regulate many important processes like growth, wound healing, and immune system function.

In this study, the researchers showed through laboratory studies that cilengitide can change the way integrins and VEGF receptors move inside blood vessels. Vascular Endothelial Growth Factor (VEGF) is a protein that stimulates growth of blood vessels.

They found that this type of angiogenesis inhibitor can actually promote cell growth and blood vessel formation instead of blocking it because it changes the way that integrin and VEGF receptors move inside blood vessels

The researchers also suggested that what they have found could be a previously unknown characteristic of drugs similar to cilengitide.

Sometimes just a small change in the way a drug is used, or a small change to its composition can have a very large effect on how it works, said Dr Lesley Walker, director of cancer information at Cancer Research UK who said this study was important because:

"It may help to explain the mixed results previously seen in patients and turn around disappointing results so people may still benefit from the drug without the potential harm."

"Other anti-angiogenesis drugs like sunitinib (Sutent) and bevacizumab (Avastin) have proven effective enough for use in the NHS but there is still need to understand why they can sometime fail. It may be that there are similar mechanisms at work," she added.

Another paper published this month in the journal Cancer Cell shows that sunitinib (Sutent), can sometimes encourage tumour growth rather than stunt it.

Hodivala-Dilke told the BBC that:

"We've got evidence now that low doses [of cilengitide] can enhance tumour growth. So there is no benefit of giving a high dose, which then drops, and then a high dose again."

However, this does not mean it won't work at all, and it is important that the trials continue, she added, "but there is this caveat".

She explained that it might be more effective to give the drug via an infusion pump which would keep the dosage at the right level.

Co-investigator Dr Andy Reynolds, of the Breakthrough Breast Cancer Research Centre at the ICR, said in a press statement:

"Our study revealed a previously unknown mechanism through which drugs such as cilengitide behave."

"These results may explain why initial results from early stage clinical trials have not been as promising as hoped," said Reynolds.

"Knowledge of this mechanism will help us develop new ways to make these drugs as effective as possible. In the future, we may be able to combine these inhibitors with other drugs to maximise their effectiveness for patients," he added.

"Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors."

Obese women may be putting themselves at greater risk of breast cancer by not undergoing regular screening. According to new research by Dr. Nisa Maruthur and her team from The John Hopkins University School of Medicine in Baltimore, USA, seriously obese women are significantly less likely to say they have undergone a recent mammography than normal weight women, especially if they are white. Maruthur's findings are published online this week in Springer's Journal of General Internal Medicine.

Breast cancer is the second leading cause of cancer death among women in the US. Mammography screening has been proven to reduce the number of deaths from breast cancer; current guidelines recommend that women over the age of 40 undergo a mammography every couple of years. Obesity is also an important risk factor for both the development of, and death from, postmenopausal breast cancer.

Maruthur and colleagues conducted a systematic review and meta-analysis of 17 studies comprising over 276,000 participants, to look at whether overweight and obese women are less likely to have had a recent mammography than normal weight women. They also looked at the differences in mammography take-up between white and black obese women in three of the studies. They found that severely obese women were 20 percent less likely to have had a recent mammography than normal weight women. However, this was not the case among black women.

The authors highlight a number of reasons why obese women may not be undergoing breast cancer screening, including a delay in taking up medical care because of poor self-esteem and body image, embarrassment, a perceived lack of respect from their health care providers and unwanted weight loss advice. According to the authors, obesity may be a marker for sub-optimal health behavior in general, of which mammography is simply one element. The authors also suggest that there are racial differences in obesity-related body image which may explain the difference in take-up of mammography between white and black women.

The authors conclude that "the main implication of our study is that a lack of routine screening mammography may explain some of the increased breast cancer mortality in obese postmenopausal women. Clinicians should be aware of this disparity in evaluating their own practices."