The next frontier in 3-D printing: Human organs

By Brandon Griggs, CNN
updated 9:43 AM EDT, Thu April 3, 2014

(CNN) -- The emerging process of 3-D printing, which uses computer-created digital models to create real-world objects, has produced everything from toys to jewelry to food.

Soon, however, 3-D printers may be spitting out something far more complex, and controversial: human organs.

For years now, medical researchers have been reproducing human cells in laboratories by hand to create blood vessels, urine tubes, skin tissue and other living body parts. But engineering full organs, with their complicated cell structures, is much more difficult.

Enter 3-D printers, which because of their precise process can reproduce the vascular systems required to make organs viable. Scientists are already using the machines to print tiny strips of organ tissue. And while printing whole human organs for surgical transplants is still years away, the technology is rapidly developing.

"The mechanical process isn't all that complicated. The tricky part is the materials, which are biological in nature," said Mike Titsch, editor-in-chief of 3D Printer World, which covers the industry. "It isn't like 3-D printing plastic or metal. Plastic doesn't die if you leave it sitting on an open-air shelf at room temperature for too long."

Lawrence Bonassar, a professor of biomedical engineering at Cornell University, with an artificial ear made via 3-D printing and injectable molds.

The idea of printing a human kidney or liver in a lab may seem incomprehensible, even creepy. But to many scientists in the field, bioprinting holds great promise. Authentic printed organs could be used for drug or vaccine testing, freeing researchers from less accurate methods such as tests on animals or on synthetic models.

Then there's the hope that 3-D printers could someday produce much-needed organs for transplants. Americans are living longer, and as we get deeper into old age our organs are failing more. Some 18 people die in the United States each day waiting in vain for transplants because of a shortage of donated organs -- a problem that Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine and a pioneer in bioprinting, calls "a major health crisis."

An 'exciting new area of medicine'

Bioprinting works like this: Scientists harvest human cells from biopsies or stem cells, then allow them to multiply in a petri dish. The resulting mixture, a sort of biological ink, is fed into a 3-D printer, which is programmed to arrange different cell types, along with other materials, into a precise three-dimensional shape. Doctors hope that when placed in the body, these 3-D-printed cells will integrate with existing tissues.

The process already is seeing some success. Last year a 2-year-old girl in Illinois, born without a trachea, received a windpipe built with her own stem cells. The U.S. government has funded a university-led "body on a chip" project that prints tissue samples that mimic the functions of the heart, liver, lungs and other organs. The samples are placed on a microchip and connected with a blood substitute to keep the cells alive, allowing doctors to test specific treatments and monitor their effectiveness.

"This is an exciting new area of medicine. It has the potential for being a very important breakthrough," said Dr. Jorge Rakela, a gastroenterologist at the Mayo Clinic in Phoenix and a member of the American Liver Foundation's medical advisory committee.

One of Organovo's engineers oversees the construction of a vascular tissue construct on a Novotel bioprinter.

"Three-D printing allows you to be closer to what is happening in real life, where you have multiple layers of cells," he said. With current 2-D models, "if you grow more than one or two layers, the cells at the bottom suffocate from lack of oxygen."

To accelerate the development of bioprinted organs, a Virginia foundation that supports regenerative medicine research announced in December it will award a $1 million prize for the first organization to print a fully functioning liver.

One early contender for the prize is Organovo, a California start-up that has been a leader in bioprinting human body parts for commercial purposes. Using cells from donated tissue or stem cells, Organovo is developing what it hopes will be authentic models of human organs, primarily livers, for drug testing.

The company has printed strips of human liver tissue in its labs, although they are still very small: four by four by one millimeter, or about one-fourth the size of a dime. Each strip takes about 45 minutes to print, and it takes another two days for the cells to grow and mature, said Organovo CEO Keith Murphy. The models can then survive for about 40 days.

Organovo has also built models of human kidneys, bone, cartilage, muscle, blood vessels and lung tissue, he said.

"Basically what it allows you to do is build tissue the way you assemble something with Legos," Murphy said. "So you can put the right cells in the right places. You can't just pour them into a mold."

Ethical concerns

Not everyone is comfortable with this bold new future of lab-built body parts, however.

A research director at Gartner Inc., the information-technology research and advisory firm, believes 3-D bioprinting is advancing so quickly that it will spark a major ethical debate by 2016.

A 3-D printer at Cornell University produces an artificial ear.

"Three-D bioprinting facilities with the ability to print human organs and tissue will advance far faster than general understanding and acceptance of the ramifications of this technology," Pete Basiliere said in a recent report.

"These initiatives are well-intentioned, but raise a number of questions that remain unanswered," Basiliere added. "What happens when complex 'enhanced' organs involving nonhuman cells are made? Who will control the ability to produce them? Who will ensure the quality of the resulting organs?"

Bioprinted organs are also likely to be expensive, which could put them out of reach of all but the wealthiest patients.

Murphy said Organovo only uses human cells in creating tissues, and doesn't see any ethical problems with what his company is doing.

"People used to worry about doing research on cadavers ... and that dissipated very quickly," he said. "We don't think there's any controversy if you're producing good data and helping people with health conditions."

Most experts, including Wake Forest's Atala, don't think we'll see complex 3-D-printed organs, suitable for transplants, for years if not decades. Instead, they believe the next step will be printing strips of tissue, or patches, that could be used to repair livers and other damaged organs.

Organovo also uses the Nuveen MMX Bio printer, which is small enough to fit into a cabinet.

"We are very eager to put pieces of tissue to work for surgical transplants," said Organovo's Murphy, who hopes his company will be ready to begin clinical trials within five years.

Of course, any use of 3-D-printed tissue in surgical procedures would require approval by the U.S. Food and Drug Administration. That review process could take up to a decade.

By then, the notion of a surgeon putting a 3-D-printed kidney into a patient may not seem so bizarre. Then again, this swiftly evolving technology may create new moral conundrums.

"The ethical questions are bound to be the same concerns we have seen in the past. Many major medical breakthroughs have suffered moral resistance, from organ transplants to stem cells," said Titsch of 3D Printer World.

"Will only the rich be able to afford it? Are we playing God? In the end, saving lives tends to trump all objections."

Source

You're not alone: Medical conspiracies believed by many

By Andrew M. Seaman

NEW YORK Wed Mar 19, 2014 7:33am EDT

(Reuters Health) - About half of American adults believe in at least one medical conspiracy theory, according to new survey results.

Some conspiracy theories have much more traction than others, however.

For example, three times as many people believe U.S. regulators prevent people from getting natural cures as believe that a U.S. spy agency infected a large number of African Americans with the human immunodeficiency virus (HIV).

J. Eric Oliver, the study's lead author from University of Chicago, said people may believe in conspiracy theories because they're easier to understand than complex medical information.

"Science in general - medicine in particular - is complicated and cognitively challenging because you have to carry around a lot of uncertainty," Oliver said.

"To talk about epidemiology and probability theories is difficult to understand as opposed to 'if you put this substance in your body, it's going to be bad,'" he said.

For the new study, he and his colleague used data from 1,351 adults who answered an online survey between August and September 2013. The data were then weighted to represent the U.S. population.

The participants read six popular medical conspiracy theories and then indicated whether they had heard of them and whether they agreed or disagreed with them.

Like the theories about conspiracies to infect African Americans with HIV and to prevent citizens from accessing alternative medicines, the other theories on the list had mistrust of government and large organizations as themes.

They include the theory that the government knows cell phones cause cancer but does nothing about it, that genetically modified organisms are being used to shrink the world's population, that routine vaccinations cause autism and that water fluoridation is a way for companies to dump dangerous chemicals into the environment.

Some 49 percent of the survey participants agreed with at least one of the conspiracies.

In fact, in addition to the 37 percent of respondents who fully agreed that U.S. regulators are suppressing access to natural cures, less than a third were willing to say they actively disagreed with the theory.

With regard to the theory that childhood vaccines cause psychological disorders like autism and the government knows it, 69 percent had heard the idea, 20 percent agreed with it and 44 percent disagreed.

The only conspiracy theory with which more than half of the respondents disagreed was that a U.S. spy agency infected a large number of African Americans with HIV.

The survey results suggest people who believe in medical conspiracy theories may approach their own health differently, the researchers said.

For example, while 13 percent of people who did not believe in any conspiracies took herbal supplements, 35 percent of those who believed in three or more theories took supplements.

Overall, the researchers say people who believed in conspiracies were more likely to use alternative medicine and to avoid traditional medicine.

"Although it is common to disparage adherents of conspiracy theories as a delusional fringe of paranoid cranks, our data suggest that medical conspiracy theories are widely known, broadly endorsed, and highly predictive of many common health behaviors," the researchers write in JAMA Internal Medicine.

Oliver said the findings may have implications for doctors.

Instead of viewing patients who believe in conspiracy theories as crazy, he said doctors should realize those patients may be less likely to follow a prescription regimen.

"It's important to increase information about health and science to the public," he said. "I think scientific thinking is not a very intuitive way to see the world. For people who don't have a lot of education, it's relatively easy to reject the scientific way of thinking about things."

SOURCE: bit.ly/1lLueQV JAMA Internal Medicine, online March 17, 2014.

Source

When are effective medications just too expensive?

doi: 10.3949/ccjm.81a.14010 Cleveland Clinic Journal of Medicine March 2014 vol. 81 3 173-175

SHIVAN J. MEHTA, MD, MBA

Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania; Center for Health Care Innovation, University of Pennsylvania, Philadelphia 

ADDRESS: Shivan J. Mehta, MD, MBA, Perelman School of Medicine, University of Pennsylvania, 1133 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104; e-mail: shivan.mehta@uphs.upenn.edu

DAVID A. ASCH, MD, MBA

Center for Health Care Innovation, University of Pennsylvania, Philadelphia; Center for Health Equity Research and Promotion, Philadelphia VA Medical Center

The era of all-oral agents for hepatitis C virus infection has begun. Previous treatments for this disease included pegylated interferon and ribavirin, which had limited effectiveness and side effects severe enough to reduce adherence and quality of life. Recent trials have documented the effectiveness of the new direct-acting antiviral agents.¹ These new drugs work better and offer the promise of an all-oral treatment regimen that avoids pegylated interferon.

See related article, page 159

But they cost a lot. Prices of more than $50,000 are estimated for a 2-to-3-month course of treatment.² These new medications reflect the kind of societal advances that justify a long-term investment in basic and clinical research. But do we value advances at any cost?

DOES COST MATTER?

Leaving aside the question of whether these particular drugs are too expensive, the general question remains whether effective therapies can ever be so expensive that we should not use them.

Does cost matter? Well, we all know that it does. We pay attention to cost in our individual purchasing and in how we think about business and government spending. And yet, while everyone agrees that we shouldn’t pay for care that provides no benefit, many of us stop at just that line, and think or act as if we can’t put a price on those elements of health care that offer some potential to save lives. It’s a comfortable position, because in going after pure waste we feel like fiscally temperate guardians of societal resources without feeling responsible for heart-rending choices about overspending on things that do work. Yet that spending threatens societal resources just as much as useless therapies.

In the end, though, it is an illogical position. The illogic is easy to understand once you walk it through: if you are unwilling to put a price on life, then you are saying that there is no price too high for any potential health benefit, no matter how small. That means you commit all your resources to health and you go bankrupt.

So, implicitly or explicitly (our society does so implicitly—and inconsistently, at that), you have to put a maximum price on life. But at that point, you are (again, implicitly) saying that when there are treatments that cost more, you shouldn’t buy them.³ Admittedly, it doesn’t sound good, and in health care, which touches us so intimately, it doesn’t feel good either.

SHOULD PHYSICIANS CARE ABOUT COST?

Many of us were taught in medical school that it isn’t the doctor’s job to think about cost. Physicians are to be clinical advocates for their patients without consideration of cost—but that can’t be right, and it isn’t right.

First, even if physicians are patient advocates first, they ought to consider cost when the patient is paying. The rise in the use of high-deductible health insurance plans has expanded the financial risk that individual patients face in their own health care decisions. Physicians may be unprepared to help patients with those decisions, but it seems like a service they ought to provide.

Second, the line between cost to the individual and cost to society is blurred at best. Our societal health care spending is nothing more than the aggregation of our individual health care spending. Even if we don’t want physicians to focus on cost when with an individual patient at the bedside or at the examination table, don’t we want societal cost to be at least in their peripheral vision?

Many obstacles impede this view. Even if physicians can keep societal costs in their peripheral vision, they certainly can’t see to the edges of the broad canvas that all of health care represents, and they have no easy decision rules for how to turn what vision they have into a decision for a particular patient.

A variety of stakeholders have succeeded in turning what might have been seen as socially responsible thinking into a dirty word. The same politicians who use the term “stewardship” when they are in favor of considering societal implications call it “rationing” when they feel the other way. As a result, some of our most important institutions—eg, Medicare—are prohibited from considering price. Commercial insurers, still smarting from the managed-care backlash of the 1990s, have limited ability to effectively manage costs while maintaining quality. In some sense, this vacuum creates an opportunity for physician leadership.

COST-EFFECTIVENESS ANALYSIS AND ITS LIMITATIONS

Cost-effectiveness analysis, which represents the health care value of a therapy as the ratio of its financial cost to its benefit (eg, cost per quality-adjusted life-year), offers a disciplined approach to these conflicts between individual good and social good.⁴

The long-term costs of hepatitis C are substantial and include multiple diagnostic tests, hospitalization, surgery, and death. A major treatment for both liver failure and hepatocellular cancer is liver transplantation, which can entail hundreds of thousands of dollars in cost for the surgery and ongoing care. Preventing just one transplant can provide enormous savings, in addition to freeing up cadaveric organs for another patient. A careful cost-effectiveness analysis could tell us whether the new direct-acting antiviral agents are worth their cost.

These analyses are appealing because they are formal and disciplined, but it turns out that they are far from value-free. Their methodology is complicated and is sensitive to subjective modeling assumptions whose implications are often not straightforward, are hard to report in the compact methods sections of manuscripts, and are harder still to interpret by most readers of these articles.

Further, these models focus exclusively on economic efficiency, so even the most carefully constructed cost-effectiveness analyses need to be tempered by a sense of social equity not captured in these models. For example, an emphasis on increasing quality-adjusted life-years will naturally lead to policy decisions that favor groups that have more life-years remaining. That may sound fine if we are comfortable with the idea that, in general, we should target our resources toward younger people rather than older people. But the same thinking means we should target our resources away from men (who don’t live as long as women) or away from members of racial minority groups (who don’t live as long as whites).

Finally, although some throw about numbers like $50,000 to $100,000 per quality-adjusted life-year as a guide, the price thresholds revealed by our current practices and policies are inconsistent. Hemodialysis is funded through Medicare by a federal mandate, but more cost-effective vaccines and preventive care are not covered to the same degree. Cost-effectiveness analyses are essential to establish a quantitative sense about the efficient use of resources, but they need to be interpreted alongside other considerations we also value. Cost-effectiveness analyses don’t take us all the way to the decision line by themselves.

WHY ARE NEW DRUGS SO EXPENSIVE?

The high cost of the new direct-acting antivirals for just months of therapy seems excessive on its face. Even though most patients will not pay these costs directly, they are borne by society through higher taxes or premiums for commercial insurance, which are paid out-of-pocket by those who purchase individual insurance, or substitute for wages in employment-based health insurance.

We know that the actual cost to manufacture these drugs is significantly less than the prices charged by pharmaceutical companies⁵ and that the government subsidizes both the research and the reimbursement for certain therapies. However, the companies need to cover the long-term costs of research and development not only for these drugs but for other drugs that did not make it through the pipeline but might have.⁶

There are at least two sides to this economy. First, the more we are willing to pay for successful drugs that go to market, the more the developers of those drugs will be willing to invest in finding new ones. If we were to pay less for individual successes, we would in the end have fewer trials and fewer overall successes.

Second, pharmaceutical companies hire economists to do their own cost-effectiveness calculations. One reason it should be no surprise that new drugs often arrive on the market at prices that are pretty close to commonly accepted thresholds for cost-effectiveness is that this is partly how they were priced in the first place. Pharmaceutical companies naturally want to price their products as high as they can. Since there is a limit to what people are willing to pay for the benefit they get in return, determining that limit and setting the price at that point helps firms extract as much of the surplus as possible.

AN OPPORTUNITY FOR LEADERSHIP

A disciplined analysis of the costs and benefits of new drug therapies is critical to any medical policy decision, rather than cost alone. There will always be a point where new treatments are too expensive—a point not based on absolute cost, but on cost relative to what is gained over and above the next best alternative.⁷ However, we should acknowledge that these analyses are based on estimates that may change over time, that they require modeling assumptions that are often subjective and opaque, and that the interpretation and implementation of these policies within their social context is just as important as the analysis of their economic efficiency.

As challenging as these decisions are, they offer an opportunity for leadership from medicine. Some organizations have already taken a stance on eliminating waste—through their participation in the Choosing Wisely initiative led by the American Board of Internal Medicine⁸ or through stands against the use of drugs and procedures that offer no benefit over cheaper alternatives.⁹ As these decisions get harder and as we aim to reduce not just zero-value care, but also low-value care, physicians have an enormous amount to contribute.

• Copyright© 2014 The Cleveland Clinic Foundation

REFERENCES

Source

Digital media could work as tool to improve health

BY RONNIE COHEN
NEW YORK Sat Feb 15, 2014 2:58am IST

(Reuters Health) - After a desperate mother in South Wales, UK, posted a video of her baby having a seizure on Facebook, one of her friends provided the diagnosis that had eluded the boy's doctor.

The discovery that Evan Owens suffers from reflex anoxic seizures, a rare but treatable disease, provided a happy ending and is just one example of the public health benefits of digital media, says a new perspective in the Journal of Public Health.

Evan's story, published in the UK's Daily Mail, illustrates how people are turning to the Internet for healthcare advice and how important it is for healthcare professionals to participate in the discussion, the perspective's lead author, Amelia Burke-Garcia, told Reuters Health. (The Daily Mail story is online here:dailym.ai/1eWaEl6.)

"There's always the risk of misinformation or false information floating around on these channels," Burke-Garcia said. "The fact that people are using them demonstrates the need for healthcare professionals to be active and share information in these environments."

Public health professionals are beginning to use digital media as a research tool and to deliver messages about everything from obesity to AIDS, the study says. "But there are many other opportunities that can be explored especially because existing platforms will evolve and new ones will emerge," Burke-Garcia said.

She runs the Center for Digital Strategy and Research at Westat, a research corporation in Rockville, Maryland. She and Dr. Gabriel Scally, from the University of the West of England in Bristol, analyzed academic and online literature to identify future directions for digital media in public health research and communications.

"Digital media is set to revolutionize the way in which health information is communicated and gathered," the researchers write in their perspective. But, they say, despite numerous studies, there has been little "effective and meaningful evaluation."

Digital media is being used to track disease spread and mobilize responses. Healthcare organizations have used it to frame debates and communicate with wide segments of the population.

One future trend the authors identify is what they call "buzz monitoring," listening in on public online conversations about health issues, like smoking or obesity, in an effort to tailor future public health announcements.

Another use of digital media connects healthcare providers and consumers in online meeting places that bring people together for a variety of purposes. As an example, Burke-Garcia said, public health workers might talk to "Mommy and Me" groups about vaccinations.

Recent research found specially created Facebook groups worked to encourage gay men to reach out for information about home HIV/AIDS testing (see Reuters Health story of September 2, 2013 here: reut.rs/1b2pANv.)

Oyinlola Oyebode, a public health researcher at University College London, told Reuters Health in an email that she has seen firsthand the power of digital media in health research. Reports of vomiting on Facebook helped her team identify an additional 80 cases in one disease outbreak, she said.

In addition, she recently ran a study examining text-message reminders and breast cancer screening. Women reminded by text were more likely to attend screening appointments, she said.

Oyebode wrote a commentary published with Burke-Garcia and Scally's perspective.

Social scientist Peter John Aspinall also was not involved in the current study but wrote his own commentary. He told Reuters Health in an email that "the more routine adoption of these technologies may represent something of a slow march given the substantial pressures on already stretched public health resources."

Aspinall, from the UK's University of Kent, warned that web-based disease surveillance "can get the trends wrong because of the lack of contextual information." For example, he said, Google Flu Trends overestimated the number of Americans stricken with flu last year.

"This has led international experts in disease surveillance to conclude that flu-tracking techniques based on the mining of web data should be seen to complement rather than substitute for traditional epidemiological surveillance networks," he said.

Asked about digital media's propensity for fear mongering, Burke-Garcia said new media is no different than old when it comes to whipping up panic.

"I don't think digital media creates fear where other channels don't," she said.

"There are downsides to the speed and the ubiquity of messages in digital. You can say that the channel creates fear. The channel also creates opportunities to combat that fear."

Though Oyebode has embraced digital media, she sees potential drawbacks, particularly if public health announcements keep people in their chairs or on their couches in front of screens.

"It might be an effective way to encourage people to make healthy lifestyle changes or to help them connect and find social support during a difficult time," she said. "And there are some particular instances, for example relating to sexual health, where it might be easier for people to seek information . . . online than face to face," Oyebode added.

"However, those developing online interventions should think about how much sedentary time their intervention will encourage."

SOURCES: bit.ly/1hggf7q, bit.ly/1gzHvcn and bit.ly/1kF3VOz Journal of Public Health, January 2014.

Source

Coffee and Cigarettes May Protect Against Liver Disease

Provided by Science Daily

Liver transplantation. PSC is the main cause for liver transplantations in Scandinavia. (Credit: Ram Gupta, Oslo University Hospital)

Dec. 14, 2013 — Coffee and cigarette smoking may protect against the rare liver disease Primary Sclerosing Cholangitis (PSC), study shows.

In a new study from Norway published inClinical Gastroenterology and Hepatology, both coffee consumption and cigarette smoking are shown to potentially protect against primary sclerosing cholangitis (PSC). This is a chronic liver disease caused by chronic inflammation of the bile ducts.

The findings are of great interest against a backdrop of increasing knowledge on coffee as a possible protective agent in other liver diseases.

The cross-sectional study was conducted by researchers at the Norwegian PSC Research Center based at Oslo University Hospital and the University of Oslo.

The study was conducted using a questionnaire about environmental exposures, and included 240 PSC patients and 245 controls.

Coffee

The study shows showed that the PSC patients had lower coffee consumption both currently and in the early adulthood, suggesting that coffee consumption could protect against the development of the disease. PSC patients who drank coffee, however, had lower levels of liver enzymes in the blood, thus suggesting a beneficial effect in the liver.

Cigarettes

Regarding cigarette smoking, only 20% of the patients reported ever daily cigarette smoking, compared with 43% of the healthy controls. In addition, cigarette smokers acquired the disease on average 10 years later than non-smokers. Taken together, these observations confirm and strengthen previous observations of smoking as a possible protective factor in PSC.

About PSC

While PSC is not a common disease, it is a severe condition affecting mostly young adults (30-40 years), and with a high risk of associated cancer of the bile ducts.

Few treatment options are available and PSC is one of the most important reasons for liver transplantation. While the possible protective effect of smoking against PSC seems rather unique to this particular liver disease, coffee consumption has been shown to protect against multiple other liver conditions including liver cirrhosis and liver cancer -- and now for the first time also against PSC.

Story Source:

The above story is based on materials provided by Oslo University Hospital, via AlphaGalileo.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Source

Surprising Discovery: Skin Communicates With Liver

Scientists covered the mice with blue latex to prevent evaporation from the skin and thus stop the heat loss. With this loss the mice stopped accumulating fat in the liver. This shows that the skin is communicating with the liver. (Credit: Birgitte Svennevig/SDU. Film: Henrik Gautier/SDU)

Dec. 6, 2013 — Researchers from the University of Southern Denmark have discovered that the skin is capable of communicating with the liver. The discovery has surprised the scientists, and they say that it may help our understanding of how skin diseases can affect the rest of the body.

Professor Susanne Mandrup and her research group in collaboration with Nils Færgeman's research group at the Department of Biochemistry and Molecular Biology at the University of Southern Denmark was actually studying something completely different when they made the groundbreaking discovery: That the skin, which is the body's largest organ, can "talk" to the liver.

"We have showed that the skin affects the metabolism in the liver, and that is quite a surprise," say Susanne Mandrup and Ditte Neess, a former student in the Mandrup research group and now laboratory manager in Professor Nils Færgeman's group.

The phenomenon was observed in the researcher's laboratory mice. The Mandrup and Færgeman groups work with so-called knock-out mice, in which a specific fat binding protein called acyl CoA binding protein has been removed (knocked out). Some knock-out mice produced by the researchers had a strange greasy fur, and they had difficulties being weaned from their mother. In the weaning period they gained less weight and showed a failure to thrive. Analyses also showed that the mice accumulated fat in the liver at weaning.

"At first we thought that the fat accumulation in the liver was linked with the fact that the gene was missing in the liver of the knock-out mice. But this was ruled out by a series of studies, and we had to find another explanation," says Ditte Neess.

She and her colleagues took another look at the rumpled and weak knock-out mice. Their fur was greasy, and they had a leaky skin from which they lost more water than normal mice.

"When they lose water, they also lose heat. We therefore asked ourselves whether this water and heat loss could be the reason why the mice accumulated fat in the liver and became weak when weaned from their mother," says Ditte Neess.

To clarify this, the researchers made ​​some mice that lacked the fat binding protein only in the skin. Similar to the full knockouts these mice had difficulties after weaning and accumulated fat in the liver. So this showed that the lack of the fat-binding protein in the skin was sufficient to induce accumulation of fat in the liver.

To get to the bottom of how a defect in the skin "talks" to the liver, the researchers decided to cover the mice with Vaseline. This would prevent water evaporating from the skin and thus stopping the heat loss. As a result the fat accumulation in the liver disappeared. But as Vaseline contains fat, that could theoretically be absorbed by the skin or ingested by the mice, the researchers were a little unsure if there were side effects from the Vaseline. A student proposed to cover the mice with liquid latex, which she found in a local sex shop.

Having covered the mice in blue latex the researchers saw that fat accumulation in the liver again disappeared.

"We believe that the leaking of water from the skin makes the mice feel cold, and that this leads to breaking down of fat in their adipose (fat) tissue. The broken down fat is then moved to the liver. The mice move energy from the tissues to the liver," Susanne Mandrup and Ditte Neess explain.

Story Source:

The above story is based on materials provided by University of Southern Denmark.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

---

Journal Reference:

1. Ditte Neess, Signe Bek, Maria Bloksgaard, Ann-Britt Marcher, Nils J. Færgeman, Susanne Mandrup. Delayed Hepatic Adaptation to Weaning in ACBP−/− Mice Is Caused by Disruption of the Epidermal Barrier. Cell Reports, 2013; DOI: 10.1016/j.celrep.2013.11.010

Source

So You Want to Be a Hepatologist?

Gastroenterology
Volume 145, Issue 6 , Pages 1182-1185, December 2013

Bruce A. Luxon

published online 21 October 2013.

John Del Valle, Section Editor

Hepatology is a discipline that has developed substantially over the past 3 decades, from one that featured many diagnoses but very few therapeutic interventions to a specialty in which we can effectively prevent and treat many liver diseases. Several therapeutic interventions for the complications of end-stage liver disease were well-described and considered standard of care, but had not been proven to be of benefit. Patients with liver disease were assigned to a variety of causes of their liver disease, but little could be done to improve their lifestyle or prevent morbidity and mortality. Liver transplantation, for instance, was still in its infancy. Other patients were correctly labeled as having inflammation of the liver and the term hepatitis was widely used. However, the exact cause of the hepatitis could not be established and hence a beneficial treatment could not be established. Fortunately, over the past 20–30 years hepatology has become a field of medicine where we can provide accurate diagnoses, beneficial treatment, and, more important, prevention of end-stage liver disease. Despite this increase in knowledge and efficiency in our medical care, the training of physicians with expertise to provide these services has not kept pace with the rapid expansion of our medical knowledge.¹ In fact, more than 10 years ago, hepatology was viewed only as a subset of the vast field of gastroenterology.

Is There a Demand for Hepatologists? 

As we made advances in the diagnosis and treatment of liver diseases, it became apparent that the field of hepatology would grow. It also became clear that manpower needs would dictate the need for physicians with special expertise to provide adequate patient care. For gastroenterology trainees, an important date was July 1, 2001, when the Medicare colon cancer screening benefit was expanded to include screening colonoscopy for average risk individuals once every 10 years. As this economic incentive became widely established, hepatology quickly became a field of specialization which was less desirable for fellows.

The American Association for the Study of Liver Diseases (AASLD) represents the largest group of physicians interested in hepatology. In 2013 the society had >4000 dues-paying members. However, only about half of these physicians are based in the United States.² Furthermore, only a few of these AASLD members indicated that their practice focuses on hepatology ≥50% of the time. Interestingly, most AASLD members in the United States are associated with an academic appointment at a teaching hospital and have their practice within a system with a liver transplant program. In 2013, there were 138 adult and pediatric liver transplant programs registered with United Network for Organ Sharing.³ There is a clear demand for hepatologists to join these transplant programs. However, many of these openings are unfilled. This is because the supplying of physicians with the required expertise in hepatology has not kept pace with the growing demand.

History of Certification of Expertise in Hepatology 

According to the membership survey of the AASLD, most current hepatologists did a fellowship in gastroenterology in which hepatology was emphasized.³ This was a personal choice of the trainee, because no specialized program existed for training in hepatology. In the mid to late 1990s, AASLD leadership commissioned a task force to determine whether hepatology was a distinct and separate entity within the field of gastroenterology. The consensus was that advanced and transplant hepatology not only had its own body of specialized knowledge and expertise, but that practicing gastroenterologists often did not consider themselves adequately prepared to care for patients with end-stage liver disease. The task force reported that most referrals to liver transplant centers and consult requests to transplant hepatologists came from gastroenterologists, not from primary care physicians, surgeons, or internists.

In 2000, the AASLD applied to the American Board of Internal Medicine (ABIM) to consider a certifying examination in transplant hepatology.⁴ The AASLD argued that advanced and transplant hepatology was clearly a distinct discipline, separate from gastroenterology; that there was a distinct body of literature which was devoted exclusively to the discipline; and that practicing gastroenterologists viewed certain colleagues as having unique expertise in hepatology.⁴

After some debate, the application was supported and the ABIM created a certifying examination, which was ready for its first administration in November 2006. This initial examination was taken by 214 ABIM-certified adult gastroenterologists. The pass rate was 88% and the minimum passing score was to answer 73% of the 175 questions correctly.⁴ After looking through various test validation statistics, the ABIM concluded the examination had performed as expected.⁵

By 2013, only 430 physicians have become board certified in transplant hepatology.⁶ Most of these candidates took the examination in the first year that it was offered because candidates' clinical experience was “grandfathered” in. Qualifying to take the transplant hepatology boards now requires specific clinical training in advanced and transplant hepatology.

Hepatology Training Pathways 

In the last 10 years, 3 pathways existed for physicians to become trained in hepatology. The first is a 1-year training program not associated with a GI training program and was not recognized by the Accreditation Council for Graduate Medical Education (ACGME). The second pathway is through an ACGME-recognized 1-year program, also separate from a GI training program. The third and most recent is an innovative pilot program that combines shortened training with new tools of medical education assessment. This last program is closely identified with a GI training program.

Advanced and Transplant Hepatology Not Associated With Gastroenterology Training 

An option that became popular in the late 1990s and early 2000s was an “isolated” fellowship devoted exclusively to advanced and transplant hepatology. These programs typically were not associated with gastroenterology training programs. They were often populated by internal medicine residents who saw the competition for traditional gastroenterology fellowships increasing and used this avenue to enhance their candidacy. In addition, many non-US graduates saw this as a way to improve their chances at either getting a residency or a gastroenterology fellowship.

These programs were typically 1-year positions with no established curriculum and had no formal recognition process. The AASLD provided support for many of these trainees in the form of competitive grants based on an institution's record of training physicians in liver disease. However, retrospectively, many of the young physicians who were supported in these programs did not turn out to be hepatologists. It is not clear how many succeeded in obtaining a gastroenterology fellowship. The author's personal experience suggests that a small minority of trainees who did this type of hepatology fellowship actually stayed in the practice of hepatology.

Many of these “isolated” hepatology training programs are now defunct. The reasons for this include their ambiguous curriculum, difficulty finding funding to provide salary support, and a lack of recognition by either the ABIM or by the ACGME.⁷

Advanced and Transplant Hepatology Training After Training in Gastroenterology 

In 2006, the ACGME allowed the creation of advanced and transplant hepatology training programs. Initial enthusiasm was high and many academic centers submitted the application paperwork to create hepatology training programs at their institutions (5).⁵ These programs require the hepatology training be done after completing gastroenterology training. Thus, a potential hepatologist selecting this route had the disadvantage of training 3 years in internal medicine, 3 years in gastroenterology, and then 1 additional year in hepatology. In addition, this route requires (by definition) that the hepatologist compete to get into a gastroenterology training program. In addition, the requirements for ABIM certification in transplant hepatology require that all candidates be board certified in gastroenterology. Thus, the requirements of the ACGME (for programs) and the ABIM (for individuals) have definitely lengthened and complicated the process of training hepatologists.

Under the current policy, the only way to become a credentialed hepatologist is to complete a 3-year fellowship in gastroenterology, complete an additional 1-year fellowship in advanced and transplant hepatology, and then pass the ABIM examinations in both gastroenterology and transplant hepatology.

However, it became clear that the ACGME and ABIM rules governing these programs discouraged trainees from entering this pathway. Currently, the ACGME website lists 39 programs that have a transplant hepatology fellowship. However, there are only 34 fellows enrolled for the 2013–2014 academic year.⁸ Given that many programs are approved for 2 fellows per year, these numbers reflect that the current paradigm for hepatology training is not succeeding in attracting hepatology trainees.

ABIM Pilot Program: Advanced and Transplant Hepatology Training “During” Training in Gastroenterology 

In 2012, the AASLD, with the input of other GI professional societies, worked with the ABIM to create a 3-year, combined GI/transplant hepatology training program. The initial goal was to create a training program that recognized and promoted the unique manpower needs in advanced and transplant hepatology. As mentioned, many of the “standard” transplant fellowship were not attracting applicants. Training directors created the template of a competency-based training program that combined training in gastroenterology as well as transplant hepatology. The training in gastroenterology per the ABIM suggestions would be assessed by the traditional standards of medical education, which existed in 2012, and the specifically developed tools of competency-based medicine education would be applied to the transplant hepatology year. This pilot program became available on July 1, 2012.⁶

The transplant hepatology pilot program sponsored by the AASLD and approved by the ABIM has several goals. The first was to be a front runner in medical education by deriving and implementing a competency-based training program using milestones and entrustable professional activities (EPAs).⁹ Milestones and EPAs are relatively new concepts in postgraduate medical training. Milestones are a series of developmental goals related to the current competencies, which are designed to help assess whether an individual trainee has met the competency. EPAs are concrete clinical activities that link to core competencies or milestones. They are designed to incorporate the professional judgment of competence by seasoned clinicians. As the trainee progresses through his education, the goal is to allow the trainee to build a collection (portfolio) of EPAs to document competence. Additional information for the internal medicine milestones is available online.⁹A second goal was to create a program that allowed trainees to sit for both gastroenterology and the transplant hepatology ABIM board examinations after they had successfully completed only 3 years of clinical training. A third goal was to produce 5–10 additional board-eligible transplant hepatologists each year.

Competency-Based Medical Education Innovations 

Following the new medical education goals of the ACGME, the transplant hepatology pilot program used EPAs to assess trainees. The supervising and oversight committee of the AASLD also developed a transplant hepatology in-service examination that will be made available to all programs participating in the pilot. Finally, competency-based medical education requires care transition measures, multisource feedback instruments, milestones, and performance measures.

Details of Incorporating the Pilot Program Into an Existing Gastroenterology Training Program 

The professional societies involved in training gastroenterologists and hepatologists did not wish to do increase competition for internal medicine residents to get into training slots. The pilot program must have an existing, traditional, ACGME-accredited transplant hepatology program. They also must have an ACGME-accredited gastroenterology program. The candidate must apply to his gastroenterology and transplant hepatology program directors, and should be judged to be competent in GI by the end of year 2 and on a trajectory to successfully complete GI training by the end of 3 years. Obviously, cooperation must exist between the gastroenterology and transplant hepatology training programs to ensure that there is sufficient volume of hepatology clinical opportunities both for the gastroenterology trainees as well as the hepatology pilot fellow. Some adjustment may be may be needed to ensure adequate manpower to cover the gastroenterology services, especially those that are not related to hepatology, such as advanced endoscopy, inflammatory bowel disease, and motility. The oversight committee felt that the transplant hepatology pilot fellows in many ways should still have similar duties to what they would have been during their third year of gastroenterology training. Specifically, the oversight committee felt that the training pilot fellow should continue in their continuity clinic, continue to perform standard endoscopies, participate in educational programs such as conferences, biopsy review, and morbidity and mortality conferences, and still take after-hours calls.

The process of identifying and approving candidates for this pilot program has been kept as simple as possible. The candidate fellow should be identified no later than the middle of the second year of training. Early identification is important to ensure that the fellow is on the “right trajectory” with regard to his/her GI clinical skills. Approval is needed from the candidate's institution Graduate Medical Education authority, typically the designated institutional official. Because the institution must have ACGME-approved transplant hepatology and gastroenterology fellowships, the candidate must get written approval from both program directors. A letter of intent is then sent to the AASLD Transplant Hepatology Pilot Program Steering Committee. If the institution and the candidate are approved, the committee recommends to the ABIM that the candidate be allowed to sit for the transplant hepatology boards after completion of 3 years of clinical training and after passing the gastroenterology boards. Current policy is that the ABIM must have documentation of the candidate's successful gastroenterology examination before the candidate will be allowed to sit for the transplant hepatology boards. This may change in the future, because there is some concern about a candidate's inability to prepare for and take both board examinations simultaneously.

Current Participation in Pilot Program 

The pilot program is in its second year. In 2012–2103), there were 4 fellows. In 2013–2014, 3 fellows are participating.¹⁰ A total of 7 programs have joined in the pilot program effort. Candidates interested in pursuing a standard 4th-year transplant hepatology fellowship or the new pilot program should contact both the GI training program and the transplant hepatology directors at the institution of their choice. Additional information is available on the AASLD website.¹¹ A specific letter written in May 2012 to all GI and transplant hepatology training program directors is available at this website. Overall feedback from program directors, both transplant hepatology and gastroenterology, has been positive.

Summary

The tremendous advances in clinical hepatology are a great success story in the practice of internal medicine. Hepatology has now evolved from an observational medical science to one that has a myriad of interventions, ranging from improved diagnostics, preventive strategies, and antiviral therapies, and, of course, liver transplantation. Therapies for viral hepatitis and liver cancer as well as the care of patients with end-stage liver disease have become increasingly complex. Care of patients with liver disease requires the special expertise of dedicated physicians. However, our training programs designed to developing physicians with this expertise have not kept pace with the medical advances. In fact, the length of the required hepatology training has been increased. Multiple barriers have been placed between internal medicine residents who are interested in hepatology and their career goal of being recognized as a hepatology expert.

Current training in transplant hepatology requires the candidate to successfully complete a traditional 3 year fellowship in gastroenterology. There are now 39 transplant hepatology programs accredited by the ACGME but these programs are having difficulty filling their training slots. The lack of success in attracting potential hepatologists is due to the competiveness of getting into gastroenterology programs, the 7 years required of post graduate training and the financial burden of perpetual training.

Under the leadership of the AASLD, the ABIM has approved a pilot program to train hepatologists that seeks to circumvent these pitfalls. Under special circumstances, candidates can complete their clinical training in both gastroenterology and hepatology in 3 years. They will be eligible to sit for the gastroenterology boards and if successful in passing the GI board examination, can sit for the transplant hepatology boards. Institutional programs and individual candidates for this pilot program are carefully selected by an AASLD committee that also has oversight into ensuring that the pilot program is innovative in its medical education. Pilot programs will utilize EPAs, newly developed milestones, a recently created transplant hepatology in-service examination, and will be monitored by many novel feedback instruments.

In summary, the growing need for physicians with an expertise in advanced and transplant hepatology has necessitated a change in our paradigm on how we train hepatologists. The future of hepatology has never looked brighter and the AASLD and its partners are committed to providing innovative educational and training avenues as we enter a new era in the world of liver diseases.

References 

Conflicts of interest The author discloses no conflicts.

PII: S0016-5085(13)01497-2

doi:10.1053/j.gastro.2013.10.023

© 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Source

Alcohol and Cancer Risk (Fact Sheet)

Provided by OncologyNurseAdvisor

October 28, 2013

What is alcohol?

Alcohol is the common term for ethanol or ethyl alcohol, a chemical substance found in beer, wine, and liquor, as well as in some medicines, mouthwashes, household products, and essential oils (scented liquids taken from plants). Alcohol is produced by the fermentation of sugars and starches by yeast.

The main types of alcoholic drinks and their alcohol content are as follows:

• Beers and hard ciders: 3-7 percent alcohol
• Wines, including sake: 9-15 percent alcohol
• Wines fortified with liquors, such as port: 16-20 percent alcohol

Liquor, or distilled spirits, such as gin, rum, vodka, and whiskey, which are produced by distilling the alcohol from fermented grains, fruits, or vegetables: usually 35-40 percent alcohol (70-80 proof), but can be higher

According to the National Institute on Alcohol Abuse and Alcoholism, a standard alcoholic drink in the United States contains 14.0 grams (0.6 ounces) of pure alcohol. Generally, this amount of pure alcohol is found in

• 12 ounces of beer
• 8 ounces of malt liquor
• 5 ounces of wine
• 1.5 ounces or a "shot" of 80-proof liquor

The federal government's Dietary Guidelines for Americans 2010 defines moderate alcohol drinking as up to one drink per day for women and up to two drinks per day for men. Heavy alcohol drinking is defined as having more than three drinks on any day or more than seven drinks per week for women and more than four drinks on any day or more than 14 drinks per week for men.

What is the evidence that alcohol drinking is a cause of cancer?

Based on extensive reviews of research studies, there is a strong scientific consensus of an association between alcohol drinking and several types of cancer (1, 2). In its Report on Carcinogens, the National Toxicology Program of the US Department of Health and Human Services lists consumption of alcoholic beverages as a known human carcinogen. The research evidence indicates that the more alcohol a person drinks—particularly the more alcohol a person drinks regularly over time—the higher his or her risk of developing an alcohol-associated cancer. Based on data from 2009, an estimated 3.5 percent of all cancer deaths in the United States (about 19,500 deaths) were alcohol related (3).

Clear patterns have emerged between alcohol consumption and the development of the following types of cancer:

• Head and neck cancer: Alcohol consumption is a major risk factor for certain head and neck cancers, particularly cancers of the oral cavity (excluding the lips), pharynx (throat), and larynx (voice box) (4). People who consume 50 or more grams of alcohol per day (approximately 3.5 or more drinks per day) have at least a two to three times greater risk of developing these cancers than nondrinkers (4). Moreover, the risks of these cancers are substantially higher among persons who consume this amount of alcohol and also use tobacco (5).

• Esophageal cancer: Alcohol consumption is a major risk factor for a particular type of esophageal cancer called esophageal squamous cell carcinoma (2). In addition, people who inherit a deficiency in an enzyme that metabolizes alcohol have been found to have substantially increased risks of alcohol-related esophageal squamous cell carcinoma (see

• Liver cancer: Alcohol consumption is an independent risk factor for, and a primary cause of, liver cancer (hepatocellular carcinoma) (6). (Chronic infection with hepatitis B virus and hepatitis C virus are the other major causes of liver cancer.)

• Breast cancer: More than 100 epidemiologic studies have looked at the association between alcohol consumption and the risk of breast cancer in women. These studies have consistently found an increased risk of breast cancer associated with increasing alcohol intake. A meta-analysis of 53 of these studies (which included a total of 58,000 women with breast cancer) showed that women who drank more than 45 grams of alcohol per day (approximately three drinks) had 1.5 times the risk of developing breast cancer as nondrinkers (a modestly increased risk) (7). The risk of breast cancer was higher across all levels of alcohol intake: for every 10 grams of alcohol consumed per day (slightly less than one drink), researchers observed a small (7 percent) increase in the risk of breast cancer. 

The Million Women Study in the United Kingdom (which included more than 28,000 women with breast cancer) provided a more recent, and slightly higher, estimate of breast cancer risk at low to moderate levels of alcohol consumption: every 10 grams of alcohol consumed per day was associated with a 12 percent increase in the risk of breast cancer (8).

• Colorectal cancer: Alcohol consumption is associated with a modestly increased risk of cancers of the colon and rectum. A meta-analysis of 57 cohort and case-control studies that examined the association between alcohol consumption and colorectal cancer risk showed that people who regularly drank 50 or more grams of alcohol per day (approximately 3.5 drinks) had 1.5 times the risk of developing colorectal cancer as nondrinkers or occasional drinkers (9). For every 10 grams of alcohol consumed per day, there was a small (7 percent) increase in the risk of colorectal cancer.

Research on alcohol consumption and other cancers:

Numerous studies have examined the association between alcohol consumption and the risk of other cancers, including cancers of the pancreas, ovary, prostate, stomach, uterus, and bladder. For these cancers, either no association with alcohol use has been found or the evidence for an association is inconsistent. 

However, for two cancers—renal cell (kidney) cancer and non-Hodgkin lymphoma (NHL)—multiple studies have shown that increased alcohol consumption is associated with a decreased risk of cancer (10, 11). A meta-analysis of the NHL studies (which included 18,759 people with NHL) found a 15 percent lower risk of NHL among alcohol drinkers compared with nondrinkers (11). The mechanisms by which alcohol consumption would decrease the risks of either renal cell cancer or NHL are not understood.

How does alcohol increase the risk of cancer?

Researchers have identified multiple ways that alcohol may increase the risk of cancer, including:

• ametabolizing (breaking down) ethanol in alcoholic drinks to acetaldehyde, which is a toxic chemical and a probable human carcinogen; acetaldehyde can damage both DNA (the genetic material that makes up genes) and proteins (see Question 5)
• generating reactive oxygen species (chemically reactive molecules that contain oxygen), which can damage DNA, proteins, and lipids (fats) through a process called oxidation
• impairing the body's ability to break down and absorb a variety of nutrients that may be associated with cancer risk, including vitamin A; nutrients in the vitamin B complex, such as folate; vitamin C; vitamin D; vitamin E; and carotenoids
• increasing blood levels of estrogen, a sex hormone linked to the risk of breast cancer

Alcoholic beverages may also contain a variety of carcinogenic contaminants that are introduced during fermentation and production, such as nitrosamines, asbestos fibers, phenols, and hydrocarbons.

How does the combination of alcohol and tobacco affect cancer risk?

Epidemiologic research shows that people who use both alcohol and tobacco have much greater risks of developing cancers of the oral cavity, pharynx (throat), larynx, and esophagus than people who use either alcohol or tobacco alone. In fact, for oral and pharyngeal cancers, the risks associated with using both alcohol and tobacco are multiplicative; that is, they are greater than would be expected from adding the individual risks associated with alcohol and tobacco together (5, 12).

Can a person's genes affect their risk of alcohol-related cancers?

A person's risk of alcohol-related cancers is influenced by their genes, specifically the genes that encode enzymes involved in metabolizing (breaking down) alcohol (13).

For example, one way the body metabolizes alcohol is through the activity of an enzyme called alcohol dehydrogenase, or ADH. Many individuals of Chinese, Korean, and especially Japanese descent carry a version of the gene for ADH that codes for a "superactive" form of the enzyme. This superactive ADH enzyme speeds the conversion of alcohol (ethanol) to toxic acetaldehyde. As a result, when people who have the superactive enzyme drink alcohol, acetaldehyde builds up. Among people of Japanese descent, those who have this superactive ADH have a higher risk of pancreatic cancer than those with the more common form of ADH (14).

Another enzyme, called aldehyde dehydrogenase 2 (ALDH2), metabolizes toxic acetaldehyde to non-toxic substances. Some people, particularly those of East Asian descent, carry a variant of the gene for ALDH2 that codes for a defective form of the enzyme. In people who have the defective enzyme, acetaldehyde builds up when they drink alcohol. The accumulation of acetaldehyde has such unpleasant effects (including facial flushing and heart palpitations) that most people who have inherited the ALDH2 variant are unable to consume large amounts of alcohol. Therefore, most people with the defective form of ALDH2 have a low risk of developing alcohol-related cancers.

However, some individuals with the defective form of ALDH2 can become tolerant to the unpleasant effects of acetaldehyde and consume large amounts of alcohol. Epidemiologic studies have shown that such individuals have a higher risk of alcohol-related esophageal cancer, as well as of head and neck cancers, than individuals with the fully active enzyme who drink comparable amounts of alcohol (15). These increased risks are seen only among people who carry the ALDH2 variant and drink alcohol—they are not observed in people who carry the variant but do not drink alcohol.

Can drinking red wine help prevent cancer?

Researchers conducting studies using purified proteins, human cells, and laboratory animals have found that certain substances in red wine, such as resveratrol, have anticancer properties (16). Grapes, raspberries, peanuts, and some other plants also contain resveratrol. However, clinical trials in humans have not provided evidence that resveratrol is effective in preventing or treating cancer (17). Few epidemiologic studies have looked specifically at the association between red wine consumption and cancer risk in humans. 

What happens to cancer risk after a person stops drinking alcohol?

Most of the studies that have examined whether cancer risk declines after a person stops drinking alcohol have focused on head and neck cancers and on esophageal cancer. In general, these studies have found that stopping alcohol consumption is not associated with immediate reductions in cancer risk; instead, it may take years for the risks of cancer to return to those of never drinkers.

For example, a pooled analysis of 13 case-control studies of cancer of the oral cavity and pharynx combined found that alcohol-associated cancer risk did not begin to decrease until at least 10 years after stopping alcohol drinking. Even 16 years after they stopped drinking alcohol, the risk of cancer was still higher for ex-drinkers than for never drinkers (18).

In several studies, the risk of esophageal cancer was also found to decrease slowly with increasing time since stopping alcohol drinking. A pooled analysis of five case–control studies found that the risk of esophageal cancer did not approach that of never drinkers for at least 15 years after stopping alcohol drinking (18).

Is it safe for someone to drink alcohol while undergoing cancer chemotherapy?

As with most questions related to a specific individual's cancer treatment, it is best for a patient to check with their health care team about whether or not it is safe to drink alcohol during or immediately following chemotherapy treatment. The doctors and nurses administering the treatment will be able to give specific advice about whether drinking alcohol is safe with particular chemotherapy drugs and/or other medications prescribed along with chemotherapy.

Selected References

1. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Alcohol consumption and ethyl carbamate Exit Disclaimer. IARC Monographs on the Evaluation of Carcinogenic Risks in Humans 2010;96:3-1383.

2. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Personal habits and indoor combustions. Volume 100 E. A review of human carcinogens. Exit Disclaimer IARC Monographs on the Evaluation of Carcinogenic Risks in Humans 2012;100(Pt E):373-472.

3. Nelson DE, Jarman DW, Rehm J, et al. Alcohol-attributable cancer deaths and years of potential life lost in the United States. American Journal of Public Health 2013;103(4):641-648.

4. Baan R, Straif K, Grosse Y, et al. Carcinogenicity of alcoholic beverages Exit Disclaimer. Lancet Oncology 2007;8(4):292-293.

5. Hashibe M, Brennan P, Chuang SC, et al. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiology, Biomarkers & Prevention 2009;18(2):541-550.

6. Grewal P, Viswanathen VA. Liver cancer and alcohol. Clinics in Liver Disease 2012;16(4):839-850.

7. Hamajima N, Hirose K, Tajima K, et al. Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. British Journal of Cancer 2002;87(11):1234-1245.

8. Allen NE, Beral V, Casabonne D, et al. Moderate alcohol intake and cancer incidence in women. Journal of the National Cancer Institute 2009;101(5):296-305.

9. Fedirko V, Tramacere I, Bagnardi V, et al. Alcohol drinking and colorectal cancer risk: an overall and dose-response meta-analysis of published studies. Annals of Oncology 2011;22(9):1958-1972.

10. Bellocco R, Pasquali E, Rota M, et al. Alcohol drinking and risk of renal cell carcinoma: results of a meta-analysis. Annals of Oncology 2012;23(9):2235-2244.

11. Tramacere I, Pelucchi C, Bonifazi M, et al. A meta-analysis on alcohol drinking and the risk of Hodgkin lymphoma. European Journal of Cancer Prevention 2012;21(3):268-273.

12. Turati F, Garavello W, Tramacere I, et al. A meta-analysis of alcohol drinking and oral and pharyngeal cancers: results from subgroup analyses. Alcohol and Alcoholism 2013;48(1):107-118.

13. Druesne-Pecollo N, Tehard B, Mallet Y, et al. Alcohol and genetic polymorphisms: effect on risk of alcohol-related cancer. Lancet Oncology 2009;10(2):173-180.

14. Kanda J, Matsuo K, Suzuki T, et al. Impact of alcohol consumption with polymorphisms in alcohol-metabolizing enzymes on pancreatic cancer risk in Japanese. Cancer Science 2009;100(2):296-302.

15. Yokoyama A, Omori T. Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers Exit Disclaimer. Alcohol 2005;35(3):175-185.

16. Athar M, Back JH, Tang X, et al. Resveratrol: a review of preclinical studies for human cancer prevention. Toxicology and Applied Pharmacology 2007;224(3):274-283.

17. Patel KR, Scott E, Brown VA, et al. Clinical trials of resveratrol. Annals of the New York Academy of Sciences 2011;1215:161-169.

18. Rehm J, Patra J, Popova S. Alcohol drinking cessation and its effect on esophageal and head and neck cancers: a pooled analysis. International Journal of Cancer 2007;121(5):1132-1137.

Source

Want data on drugs? Look for clinical study reports

By Andrew M. Seaman

NEW YORK | Thu Oct 24, 2013 2:22am IST

NEW YORK (Reuters Health) - For information on how drugs work and affect people, a new study says regulatory reports that are rarely published are better sources than the typical documents that are publicly available.

German researchers found that so-called clinical study reports produced by pharmaceutical companies had complete information on 86 percent of study outcomes that are relevant to patients. In contrast, only about 39 percent of those outcomes were found in other sources, such as studies published in academic journals.

"For the first time, we know how much information we can gain from the types of documents we investigated," lead author Beate Wieseler said.

Wieseler is the head of drug assessment at the Institute for Quality and Efficiency in Health Care (IQWiG). IQWiG is a German agency that examines the risks and benefits of medical interventions.

Extra information is needed for various reasons, including the creation of medical guidelines and treatment decisions between doctors and patients, she said.

But clinical study reports, which can be hundreds or thousands of pages long, are not usually available to the public.

"I don't know when it was decided or how it was decided, but the (U.S. Food and Drug Administration) considers this information proprietary and doesn't give it to anyone else," Dr. Joseph Ross said.

Ross, who was not involved in the new study, has researched the availability of study results at the Yale School of Medicine in New Haven, Connecticut.

For the new analysis, published in PLOS Medicine, Wieseler and her colleagues analyzed trials on 16 drugs that IQWiG examined between 2006 and 2011.

They compared the information in the private clinical study results to publicly available sources, such as academic journals, the U.S. government-run website clinicaltrials.gov and a registry managed by the World Health Organization, to see which included more information on patient-relevant outcomes.

Those outcomes include events such as the number of study participants who died or experienced serious side effects, how patients responded to the drug and effects it had on their quality of life.

"The thing that's interesting about this report is that clinical study results are not systematically available so people have not been able to study it," Ross said.

Overall, the researchers identified 1,080 patient-relevant outcomes for the drugs. Of those, the clinical study reports had complete information on almost nine out of 10. The publicly available sources, however, only had complete information on about four of 10.

"It's not that surprising that unpublished clinical study reports have more data and results than published study results," Ross said.

Wieseler said that the U.S. Food and Drug Administration (FDA) and its European counterpart the European Medicines Agency could start publishing clinical study reports on their websites to give people access to the data.

A FDA spokesperson, however, told Reuters Health in an email that federal law prohibits the agency from "making a fair amount of clinical data publicly available."

"The issue of clinical trial data sharing - for a lack of better word - is a hot topic at the moment," Jeff Francer, vice president and senior counsel at the Pharmaceutical Research and Manufacturers of America (PhRMA), said.

PhRMA represents biopharmaceutical researchers and biotechnology companies.

"In many cases, companies and researchers have been sharing data for quite some time really under the radar," he said. "And I think companies are comfortable sharing clinical data with qualified researchers" as long as they protect patient privacy and use the data in an appropriate way.

In July, PhRMA and the European Federation of Pharmaceutical Industries and Associations adopted Principles for Responsible Clinical Trial Data Sharing (onphr.ma/1ie4SYy).

Under those principles, which take effect January 1, companies will make synopses of the clinical study reports that are submitted to government approval organizations available to the public.

"Each company is going to be going about it a different way," Francer said. "The key is that all of our members will have information on their websites about where (the public) can find this information."

As part of the adopted principles, researchers and scientists can also request clinical trial data from companies for medicines and indications approved in the U.S. and the European Union.

Preparing to share patient-level data takes the most work, according to Francer.

For example, companies need to address privacy commitments that are made to trial participants, create data request applications and put together boards to review those requests.

Implementing the principles will be an evolutionary process, Francer said.

"We also hope the academic community and government researchers will be just as open as industry researchers are going to be starting now," he added.

Ross said making clinical trial data available will help patients better understand the risks and benefits of drugs and medications.

"It needs to be in a place where people can access it and understand it to make informed decisions on what to use," he said.

SOURCE: bit.ly/1bfq8L3 PLOS Medicine, online October 8, 2013.

Source

Family caregivers live longer than their peers

By C. E. Huggins

NEW YORK | Fri Oct 18, 2013 5:04pm EDT

NEW YORK (Reuters Health) - Caring for a disabled family member can be overwhelmingly hard. But caregivers may live longer than those who don't bear such responsibilities, new research suggests.

In a nationwide study, adults who provided care for a chronically ill or disabled family member had a lower death rate than a similar group of non-caregivers.

The finding is something of a surprise.

In the past, researchers have found just the opposite - an increased risk of death as well as poorer mental and physical health among caregivers. Such detrimental health effects have been found among people caring for a disabled spouse or a person with dementia, for example.

"(We want to) emphasize the positive message that caregiving is a healthy thing that we should be doing in our families," lead study author Dr. David L. Roth, director of the Johns Hopkins University Center on Aging and Health, told Reuters Health.

Dolores Gallagher-Thompson, who directs the Geriatric Education Center at Stanford University School of Medicine in California told Reuters Health the current study's findings are "surprising… because prior studies did find an association between caregiver stress and mortality."

Gallagher-Thompson pointed out that the caregivers included in Roth's study were not heavily stressed, however. They didn't all have their ill family member living with them full time. Some caregivers may have just visited their charges, the report indicates.

The study also did not distinguish between caregivers of people with dementia and those with other conditions.

"Previous studies that have reported high stress and increased mortality have focused on dementia," said Gallagher-Thompson.

Roth noted that poorer health among caregivers is "undoubtedly true" in some cases, particularly among those caring for people with dementia. However, "caregiving stress has been over exaggerated," he said.

Of the 3,503 caregivers included in the study, over 80% said they were experiencing either no mental or emotional strain or only a moderate level of such strain.

Only 578 - or less than one in five - felt their caregiving caused them "high strain."

Roughly two thirds of the caregivers were female. About a third were adult children, and about one in five were spouses. Slightly more than half provided care for less than 14 hours a week.

Regardless of the nature of their responsibilities, caregivers appeared to reap benefits from their own selflessness. Death rates were 18% lower among caregivers than among their non-caregiving counterparts, Roth and his team report in the American Journal of Epidemiology.

During the 2003-2012 study period, about 7.5 percent of caregivers died, compared to about 9 percent of the same number of noncaregivers.

"In a way you can say this is good news," said Gallagher-Thompson, who was not involved in the study. "If you‘re caring for someone with long-term (illness or disability in some cases), it may actually provide you with some health benefits."

Reasons for the lower rate of death among caregivers may have to do with their own self-selection, Roth said. Considering the low number of spouse caregivers included in the study, the non-spouse caregivers who chose to provide care to their family members "may be healthier, better adjusted people who have their own house in order," he said.

Gallagher-Thompson thinks maybe altruism, spirituality, and resilience among caregivers also played a role. "Some caregivers are able to roll with the punches," she said.

The study's sample was drawn from the national Reasons for Geographic and racial Differences in Stroke (REGARDS) Study of African American and white adults aged 45 years and older. Study participants were largely recruited from the southern region of the United States. Caregivers from this sample were statistically matched with noncaregivers according to a number of factors, including age, race, gender, educational and income level, self-rated health, and mental status.

Still, the narrow focus on only African American and white adults limits the generalizability of this study's findings, said Gallagher-Thompson. We have "no idea whether these findings may apply to other races, cultures, or ethnicities."

SOURCE: bit.ly/H6ejhF American Journal of Epidemiology, online October 3, 2013.

Source

The first inpatient program to treat internet addiction has opened

Four beds ready to treat Internet addicts

By Ben Tinker, CNN

updated 7:10 AM EDT, Sat September 7, 2013

The majority of Internet addicts are consumed by playing games, experts say.

(CNN) -- High above the frozen Potomac River in the nation's capitol, Ryan Van Cleave stood on the Arlington Memorial Bridge, contemplating his life. It was New Year's Eve 2007, and the married father of two asked himself, "Is this really something I'm thinking about? Is my life really this out of control?"

At the precise moment he decided not to jump, Van Cleave slipped on a patch of ice and nearly fell to his death, 100 feet below. Then he took a deep breath and stepped back from the edge.

Van Cleave, an accomplished writer and college professor, had been laid off by his prestigious university as he descended into the depths of Internet addiction. He was playing online games for up to 80 hours a week. He was avoiding his real-life friends and ignoring his wife.

"I got so far into it," he says, "I couldn't realize how I got there."

Like many others who say they are addicted to the Internet, Van Cleave likens his addiction to alcoholism.

"A beer a day becomes a case a day," he says. "You can't stop, no matter how much you want to."

"The real problem," Van Cleave adds, "is that most people laugh at you and don't consider it a serious thing."

That sentiment could change on Monday, when the country's first inpatient treatment program for Internet addiction opens at Bradford Regional Medical Center in Pennsylvania.

"I've been studying Internet addiction since 1994," says Dr. Kimberly Young, a professor at St. Bonaventure University and the psychologist who founded the program at Bradford Regional. "When you talk about the controversy behind it, laughing it off, that's often been the case with my work."

The program is designed to accommodate four patients at a time, who all begin and end their treatment on the same day. The addicts' 10-day stay begins with a 72-hour "digital detox," followed by a full psychological evaluation.

Young and Dr. Roger Laroche, the medical director of Bradford Regional's Psychiatry department, expect to see withdrawal symptoms in their patients similar to those seen in hardcore drug addicts. Some, they say, will need to be medicated to make it through the detox.

"We're really behind other countries in treating this problem," says Young. "China, Korea and Taiwan all have treatment centers. Here in the United States, people who need treatment don't have anywhere to go. Now, we finally have something to offer people."

Because Internet addiction is not classified as a mental illness in the American Psychiatric Association's Diagnostic and Statistical Manual (often referred to as the "psych bible"), none of the program's $14,000 cost will be covered by insurance.

Dr. Allen Frances, the chairman of the DSM-IV and professor emeritus at Duke University, says there's little doubt that some people could indeed suffer from an Internet addiction. But he believes the research is premature.

"The concern is that there will not be a clear, bright line in between a true Internet addiction and the rest of us, who are using it recreationally," he says.

"People can spend 10 hours a day in front of a screen, blow off their wives, blow off their work, but that doesn't necessarily mean they're addicted," says Frances. "Addiction implies a pattern of use that you can't stop." The compulsion continues, even though time spent online is no longer productive or enjoyable.

Some studies show that the same areas of the brain that light up when alcohol and drug addicts get their fix light up when Internet addicts log on. An addict, by nature, is seeking a rush of dopamine, the neurotransmitter that is associated with feelings of reward and pleasure.

"That is a very critical aspect, as far as what separates addiction from just a bad habit," says Laroche. "We literally are talking about someone who has jeopardized his life and every aspect of it."

Dig deeper into the new Diagnostic and Statistical Manual, the DSM-V, and you'll find an entry for "gaming disorder" in Section III, meaning the American Psychiatric Association believes the condition warrants further research before it can be formally classified as a mental disorder.

Most Internet addicts, it seems, are plagued by an addiction to online games, more so than other online activities such as looking at porn, shopping or using social media.

Such was the case for Van Cleave who chronicled his experience in "Unplugged: My Journey into the Dark World of Video Game Addiction."

Van Cleave began gaming when he was a child.

"At college," he says, "I suddenly had a lot of unsupervised time. I started gaming exponentially more. If you don't study much, you have even more free time."

Eventually, Van Cleave reached a "crisis point," buried for up to 80 hours a week in World of Warcraft (a role-playing game in which you can "join thousands of mighty heroes in an online world of magic and limitless adventure.")

Van Cleave lost his job, some friends, and was barely able to save his marriage. "I pushed it awfully close to the line by not being available for a long time," he says.

"It was so obvious these things were happening, but I couldn't see it because I was knee-deep in the problem."

The foreword for Van Cleave's book was written by Dr. Mark Griffiths, a professor at Nottingham Trent University in the United Kingdom, who studies behavioral addictions in the School of Social Sciences. He says Internet addiction has five key criteria:

1. Salience: The Internet becomes the most important activity in the person's life, affecting feelings, behaviors and thoughts.

2. Mood modification: The person receives an emotional "buzz" from using the Internet.

3. Tolerance: The person becomes acclimatized, requiring increasing amounts of Internet time to get that "buzz."

4. Withdrawal symptoms: Abruptly ceasing Internet activity can cause the personal emotional or physical distress.

5. Relapse: The addict tends to fall back into the same behavior very easily, even after years of abstinence or control.

"When you see that behavior," says another recovering addict, Kevin Roberts, "it's only the tip of the iceberg. You're often going to find underlying issues."

In Roberts' case, the underlying mental health issues turned out to be ADHD and anxiety, which both went undiagnosed until his Internet addiction spun out of control.

It was good friends who had been through AA, dealing with addiction themselves, who recognized Roberts' categorical consumption with gaming had reached addictive proportions.

Unlike van Cleave, Roberts went on binges.

"I would go through periods when I wouldn't indulge," he says. Other times, he would play real-time strategy games for weeks at a time, at least eight to 12 hours a day. These binges were usually set off by an emotional trigger. "I would often be sleep-deprived, sometimes going a whole day or two without sleeping."

Roberts likened himself to a functional drunk.

"I held a job and paid my bills," he says. "I wasn't real successful at relationships, because of 'the screen,' but I didn't know that at the time."

While he was able to keep it together for a while, thanks in part to his being self-employed, Roberts eventually began to lose clients.

"I even lost money after performing work for someone," he says, "because I was too busy gaming to send out an invoice."

He lost standing in his profession that he may never gain back.

"I eventually stopped gaming," Roberts says, "because the thrill became less and less, even as I played more and more."

He and Van Cleave are among the minority of Internet addicts, experts say, who have been able to break their bad habits without an extreme intervention.

Roberts wrote a book about his experience, "Cyber Junkie: Escaping the Gaming and Internet Trap." Perhaps more importantly, he joined a cyberaddiction support group. "We're always there for each other," he says. "It's our 'Vitamin C,' C being for community."

It's that sense of camaraderie that Young hopes to evoke from her patients at Bradford General. "There's a group dynamic in having them be in a class together," she says. "There's a support system that builds up."

It's worth noting that reSTART, the country's first retreat center program for Internet addiction, opened in 2009. A 45-day retreat to "disconnect and find yourself" at reSTART costs $22,000, after which patients have the option to extend their retreat for $421 a day, depending on their individual treatment needs.

Van Cleave underscores the importance of getting professional help and learning, quite simply, how to properly think and function again in daily life. "Alcoholics can stay out of bars and restaurants that serve booze, but an Internet addiction is like an eating disorder," he says.

"They have to relearn how to eat, what foods to avoid, what stores to avoid," says Laroche, employing the same metaphor.

But Frances is worried a treatment regimen that could and should be applied to tens of thousands of people will instead be applied to millions. "I'm concerned there's so much publicity about these four lousy beds," he says. "This is being commercialized prematurely."

"Before developing clinical programs, we should have the research," says Frances. "This is a dangerous sign of a fad diagnosis. Unfortunately, the history of psychology is a history of fads like this."

"Remember," counters Young, "when Betty Ford first admitted she was an alcoholic, we didn't have people believing it was actually a problem until she came around and talked about her own problems with it. This is a place for people to go for help, and that we hope will help everyone around them stop taking Internet addiction so lightly."

Source