Large, Prospective Study Finds Long-Term Obesity Is Associated with Poorer Pancreatic Cancer Survival

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In this News Digest:

- Summary of a study being published online October 21, 2013 in the Journal of Clinical Oncology, reporting that patients with pancreatic cancer who were overweight or obese years before their diagnosis tend to have more advanced disease at diagnosis and shorter survival.

- The findings add to increasing evidence linking obesity with cancer, suggesting that maintaining a healthy body weight not only reduces the risk of developing certain cancers, but may also improve outcomes after a cancer diagnosis.

- Quote for attribution to Smitha Krishnamurthi, MD, American Society of Clinical Oncology Cancer Communications Committee member and gastrointestinal cancers expert

Newswise — New results from a prospective study published in the Journal of Clinical Oncology show that patients with a body mass index (BMI) in the obese range live on average two to three months less after a pancreatic cancer diagnosis, compared with healthy weight patients, even after adjusting for factors that are known to predict survival for patients with this disease, such as age and disease stage. This association was statistically strongest for people who were overweight two decades before their diagnosis.

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Most patients with pancreatic adenocarcinoma, which accounts for more than 90% of new cases, survive less than a year after their diagnosis.

Obesity is a major public health problem in the United States and many other countries around the world. While it is well known that obesity is a risk factor for heart disease and diabetes, it is becoming increasingly clear that it is also associated with cancer risk and outcomes. In fact, scientists predict that obesity will become the leading preventable cause of cancer in the near future.

Several prior studies have shown that elevated BMI increases the risk of developing pancreatic cancer, but thus far there has been little research on whether BMI affects the aggressiveness of the disease or survival after diagnosis.

“This study adds to mounting evidence for the role of weight control in improving outcomes for patients with cancer. It also reinforces the importance of maintaining a healthy weight throughout your life, which may lead to better outcomes after diagnosis and help prevent pancreatic cancer from developing,” said senior study author Brian M. Wolpin, MD, MPH, an assistant professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School in Boston, MA. “While our findings will not affect the way we treat patients today, they provide new leads for investigating the molecular pathways that may be responsible for the survival difference between obese and healthy-weight patients. Hopefully, in the future, that research will bring new approaches for treatment of pancreatic cancer.”

Researchers evaluated the association between patients’ BMI in 1986 and survival after diagnosis of pancreatic cancer among participants from two large prospective cohort studies – the Nurses’ Health Study and the Health Professionals Follow-Up Study. Participants of those studies were surveyed on medical history, health behaviors, and lifestyle choices. The present study assessed 902 cases of pancreatic adenocarcinoma that were diagnosed during a 24-year period.

Overall, the median length of survival after diagnosis for those patients was five months. According to Dr. Wolpin, on average, healthy weight patients (BMI less than 25 kg/m2) lived 2 to 3 months longer than obese patients (BMI greater than or equal to 35 kg/m2). The association between higher prediagnostic BMI and shorter survival persisted after adjusting for differences in age, gender, race/ethnicity, smoking status, and disease stage. Obese patients were also more likely to be diagnosed with advanced disease – 72% of obese patients had metastatic disease at diagnosis compared to 59% of healthy-weight patients.

The association between BMI and survival was even stronger among the 202 patients with high BMI assessed 18-20 years before diagnosis. Assuming that most people remain overweight once they gain weight, according to Dr. Wolpin, this finding suggests that being overweight for a prolonged period of time leads to worse outcomes. This study also suggests further avenues of research on the link between obesity and cancer. For example, it is not yet clear if the same changes that promote tumor development in obese people also affect the aggressiveness of the tumor. Several ongoing studies are already exploring metabolic (energy and nutrient processing) pathways and genomic changes in relation to obesity and cancer. This work might reveal whether tumors that develop in obese people are susceptible to different treatments than tumors that develop in healthy-weight people.

This research was funded in part by a 2009 Conquer Cancer Foundation of ASCO Career Development Award to Brian Wolpin.

ASCO Perspective:
Smitha Krishnamurthi, MD, ASCO Cancer Communications Committee member and gastrointestinal cancers expert
“While previous retrospective studies suggested a link between obesity and pancreatic cancer survival, the prospective nature of this study makes the findings more reliable. An interesting aspect of this study is that it suggests that obesity, particularly chronic obesity, increases the risk of death from pancreatic cancer. This study, however, could not distinguish if the increased risk of death was due to metabolic and inflammatory changes that accompany obesity or due to other health complications of obesity.”

The full study can be found online at the Journal of Clinical Oncology.

About the Journal of Clinical Oncology:
Journal of Clinical Oncology, the flagship journal of the American Society of Clinical Oncology, is a leader in reach, readership, impact, and influence. With a focus on significant clinical oncology research, Journal of Clinical Oncology publishes over 1,000 articles in 36 issues a year.

About ASCO:
Founded in 1964, the American Society of Clinical Oncology (ASCO) is the world's leading professional organization representing physicians who care for people with cancer. With more than 30,000 members, ASCO is committed to improving cancer care through scientific meetings, educational programs and peer-reviewed journals. ASCO is supported by its affiliate organization, the Conquer Cancer Foundation, which funds ground-breaking research and programs that make a tangible difference in the lives of people with cancer. For ASCO information and resources, visit www.asco.org. Patient-oriented cancer information is available at www.cancer.net.

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New Study Indicates Risk of Amazon Rainforest Dieback Due to Global Warming is Higher than Previously Projected

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Newswise — (BOSTON) A new study co-authored by Boston University Professor of Earth & Environment Ranga Myneni suggests the southern portion of the Amazon rainforest is at a much higher risk of dieback due to climate change than projections made in the latest report by the Intergovernmental Panel on Climate Change (IPCC). If severe enough, the loss of rainforest could cause the release of large volumes of the greenhouse gas carbon dioxide into the atmosphere. It could also disrupt plant and animal communities in one of the regions of highest biodiversity in the world.

Using ground-based rainfall measurements from the last three decades, the researchers found that since 1979, the dry season in southern Amazonia has lasted about a week longer per decade. At the same time, the annual fire season has become longer. According to the study, the most likely explanation for the lengthening dry season is global warming.

“The dry season over the southern Amazon is already marginal for maintaining rainforest,” says Rong Fu, co-author and professor at The University of Texas at Austin’s Jackson School of Geosciences Fu. “At some point, if it becomes too long, the rainforest will reach a tipping point.”

The new results are in stark contrast to forecasts made by climate models used by the IPCC. Even under future scenarios in which atmospheric greenhouse gases rise dramatically, the models project the dry season in the southern Amazon to be only a few to ten days longer by the end of the century and therefore the risk of climate change-induced rainforest dieback should be relatively low.

The report appears this week in the journal Proceedings of the National Academy of Sciences.

“The length of the dry season in the southern Amazon is the most important climate condition controlling the rainforest,” says Fu. “If the dry season is too long, the rainforest will not survive.”

To see why the length of dry season is such a limiting factor, imagine there is heavier than usual rainfall during the wet season. The soil can only hold so much water and the rest runs off. The water stored in the soil at the end of the wet season is all that the rainforest trees have to last them through the dry season. The longer the dry season lasts, regardless of how wet the wet season was, the more stressed the trees become and the more susceptible they are to fire.

The researchers say the most likely explanation for the lengthening dry season in the southern Amazon in recent decades is human-caused greenhouse warming which inhibits rainfall in two ways: First, it makes it harder for warm, dry air near the surface to rise up and freely mix with cool, moist air above. And second, it blocks cold front incursions from outside the tropics that could trigger rainfall. The climate models used by the IPCC do a poor job representing these processes, which might explain why they project only a slightly longer Amazonian dry season, says Fu.

The Amazon rainforest normally removes the greenhouse gas carbon dioxide from the atmosphere, but during a severe drought in 2005, it released 1 petagram of carbon (about one tenth of annual human emissions) to the atmosphere.

“The more severe 2010 drought impacted twice the forested area than the 2005 drought and could have likely resulted in substantial carbon loss from the forests,” says Myneni, who has previously studied these droughts with NASA satellite sensor data.

Myneni and his colleagues estimate that if dry seasons continue to lengthen at just half the rate of recent decades, the Amazon drought of 2005 could become the norm, rather than the exception, by the end of this century.

Some scientists have speculated that the combination of longer dry seasons, higher surface temperatures and more fragmented forests due to ongoing human-caused deforestation could eventually convert much of southern Amazonia from rainforest to savanna.

Earlier studies have shown that human-caused deforestation in the Amazon can alter rainfall patterns. But the researchers didn’t see a strong signal of deforestation in the pattern of increasing dry season length. The dry season length increase was most pronounced in the southwestern Amazon while the most intense deforestation occurred in the southeastern Amazon.

Because the northwestern Amazon has much higher rainfall and a shorter dry season than the southern Amazon, the researchers think it is much less vulnerable to climate change.

The co-authors of this study include Rong Fu, Lei Yin, Robert Dickinson, Lei Huang and Sudip Chakraborty at The University of Texas at Austin’s Jackson School of Geosciences; Wenhong Li at Duke University; Paola A. Arias at Universidad de Antioquia in Colombia; Katia Fernandes at Columbia University’s Lamont-Doherty Earth Observatory; Brant Liebmann at the National Oceanic & Atmospheric Administration (NOAA); Rosie Fisher at the National Center for Atmospheric Research; and Ranga Myneni at Boston University.

This work is supported by the National Science Foundation (AGS 0937400) and NOAA Climate Program Office Modeling, Analysis, Prediction and Projection Program (NA10OAAR4310157) and the NASA Earth Science Division.

Note to Reporters: A preprint of the article is available to journalists on the following secure reporters-only web site: http://www.eurekalert.org/pio/pnas.php

About Boston University—Founded in 1839, Boston University is an internationally recognized private research university with more than 30,000 students participating in undergraduate, graduate, and professional programs. As Boston University’s largest academic division, the College and Graduate School of Arts & Sciences is the heart of the BU experience with a global reach that enhances the University’s reputation for teaching and research. In 2012, BU joined the Association of American Universities (AAU), a consortium of 62 leading research universities in the United States and Canada.

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UTHealth Researchers Study Device for Atrial Fibrillation at Memorial Hermann Heart & Vascular Institute

Newswise — HOUSTON – (Oct. 10, 2013) – A clinical trial evaluating a cardiac plug for the prevention of stroke in patients with atrial fibrillation has been launched by cardiology researchers at The University of Texas Health Science Center at Houston (UTHealth) Medical School.

In September, UTHealth cardiologists implanted the state’s first AMPLATZER™ Cardiac Plug (ACP) in a patient at the Memorial Hermann Heart & Vascular Institute-Texas Medical Center (HVI). The study will determine if the transcatheter device is safe and effective in preventing blood clots from migrating out of the left atrial appendage in patients with non-valvular atrial fibrillation who are at high risk for stroke.

“Atrial fibrillation is a common problem and patients need blood thinners to help prevent stroke,” said Pranav Loyalka, M.D., co-principal investigator of the Houston study, associate professor in the Program of Advanced Heart Failure at the UTHealth Medical School and associate chief of the medical division at the Center for Advanced Heart Failure at HVI. “AMPLATZER™ is one of the devices being studied that could give patients the ability to not take blood thinners.”

Atrial fibrillation is the most common type of arrhythmia, a problem with the rate or rhythm of the heartbeat caused by dysfunctional electrical activity. The heart can beat too fast, too slow or irregularly. It causes blood to pool in the atria, the heart’s upper two chambers, causing an inadequate supply of blood to pump into the ventricles, the lower chambers.

“When the blood pools in the atria, blood clots can form in the left atrial appendage, the site of 90 percent of blood clots associated with atrial fibrillation,” said Ramesh Hariharan, M.D., co-principal investigator and professor and medical director of the Complex Arrhythmia Center at the UTHealth Medical School and HVI.

An estimated 2.7 million Americans suffer from atrial fibrillation, which causes 20 percent of all ischemic strokes, the most common form of stroke. A person with atrial fibrillation is five times more likely to have a stroke.

“Symptoms of atrial fibrillation can include a racing heart and shortness of breath,” said Biswajit Kar, M.D., co-investigator, professor in the Program of Advanced Heart Failure at UTHealth and chief of the medical division at the Center for Advanced Heart Failure at HVI. “Over time, it can lead to heart failure.”

The most common blood thinners prescribed for atrial fibrillation are warfarin and dabigatran.

“The biggest drawback of warfarin is that patients need regular blood tests to check levels of the drug, which typically keep changing, causing cardiologists to adjust the dosage to prevent dangerous bleeding,” said Richard Smalling, M.D., co-investigator, professor and the Jay Brent Sterling Professor of Cardiovascular Medicine and James D. Woods Distinguished Chair of Cardiovascular Medicine at the UTHealth Medical School and interventional cardiologist at HVI.

“Dabigatran remains at more consistent levels in the body but there is no reversal agent for it, so if a person is in an automobile or other accident, there is a risk for excessive bleeding,” said Saumya Sharma, M.D., co-investigator, assistant professor in the Complex Arrhythmia Center at UTHealth and cardiologist at HVI.

The AMPLATZER™ plug is a self-expanding device made from nitinol mesh to seal the left atrial appendage, minimizing the chance of blood clots migrating into bloodstream. Patients usually have a one-night hospital stay.

“It’s like a windsock,” Loyalka said. “It plugs it so that nothing can get through and we believe this can help prevent stroke.”

The multiple-site study will enroll between 400 and 3,000 patients. It is randomized with two patients receiving the device and one patient receiving traditional medical treatment using long-term, blood-thinning medication. For more information, call the Center for Advanced Heart Failure at Memorial Hermann Heart & Vascular Institute-Texas Medical Center at (713) 704-4300.

Study Finds Racial and Social Disparities in Kidney Allocation Among Young Transplant Recipients

 

• Among kidney transplant recipients younger than 40 years of age, African Americans and individuals with less education were more likely to receive lower-quality organs than Caucasians and those with college degrees.
• African Americans with higher education levels were not more likely to receive a lower-quality kidney than Caucasians with college degrees.

Newswise — Washington, — Among younger kidney transplant recipients, a disproportionate number of African Americans and individuals with less education receive organs that are of lower quality or are considered marginal, according to a study appearing in an upcoming issue of the Clinical Journal of the American Society of Nephrology (CJASN). The findings suggest that there are racial and social disparities in the allocation of transplanted organs that need to be addressed.

Older kidney disease patients who have a high risk of dying while on dialysis may benefit from accepting a so-called extended criteria donor (ECD) kidney—which is more likely to fail than a standard criteria donor kidney—rather than remaining on a transplant wait list. But younger patients and those with short wait times are usually better off holding out for a standard criteria donor kidney. Despite this, some young patients still end up receiving ECD kidneys.

Rajesh Mohandas MD, MPH, Mark Segal MD, PhD (University of Florida), and their colleagues looked to see if demographic factors play a role in whether younger patients accept ECD kidneys. They analyzed all first single-kidney transplants documented in the United States from 2000 to 2009 in patients 18 to 40 years of age and waitlisted less than three years.

Among the major findings:
• Of 13,615 ECD transplants, 591 (4.3%) kidneys went to recipients between 18 and 40 years of age who were waitlisted less than three years.
• African Americans were 1.7 times more likely to receive an ECD kidney than Caucasians.
• Individuals with less education were 2.3 times more likely to receive an ECD kidney than those with a college degree; however, African Americans with higher education levels were not more likely to receive such a lower-quality kidney than Caucasians with college degrees.

“To our knowledge, this is the first report showing that there are racial and social disparities in the quality of allocated transplanted organs. Understanding that such disparities exist is the essential first step to addressing inequalities in health care and to attempt to improve patient outcomes,” said Dr. Mohandas. He added that it is important to ensure that kidney transplant candidates are not just informed, but also educated about their choices.

Study co-authors include Michael Casey, MD, Robert Cook, MD, MPH, Kenneth Lamb, PhD, and Xuerong Wen, MS.

Disclosures: The authors reported no financial disclosures.

The article, entitled “Racial and Socioeconomic Disparities in the Allocation of Extended Criteria Donor Kidneys,” will appear online at http://cjasn.asnjournals.org/ on October 10, 2013, doi: 10.2215/CJN01430213.

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Founded in 1966, and with more than 14,000 members, the American Society of Nephrology (ASN) leads the fight against kidney disease by educating health professionals, sharing new knowledge, advancing research, and advocating the highest quality care for patients.